#09#
Revisiones-Ciencias
Básicas (todas) *** Reviews-Basic Sciences
AGENTES
INMUNOSUPRESORES *** IMMUNOSUPPRESSIVE COMPOUNDS
(Conceptos
/ Keywords: Immunosuppressive comp; Muromonab-cd3; Sirolimus; Tacrolimus;
Cyclosporine; Mycophenolic acid; Antilymphocyte serum; Immunosuppressive comp.
used in oncology, etc).
Enero /
January 2001 --- Marzo / March 2004
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Only articles written in Spanish and/or English are included.
[1]
TÍTULO / TITLE: - Integration of growth
factor and nutrient signaling: implications for cancer biology.
REVISTA
/ JOURNAL: - Mol Cell 2003 Aug;12(2):271-80.
AUTORES
/ AUTHORS: - Shamji AF; Nghiem P; Schreiber SL
INSTITUCIÓN
/ INSTITUTION: - Harvard Biophysics Program, Harvard
University, 12 Oxford Street, Cambridge, MA 02138, USA.
RESUMEN
/ SUMMARY: - Signaling networks that promote cell
growth are frequently dysregulated in cancer. One regulatory network, which
converges on effectors such as 4EBP1 and S6K1, leads to growth by promoting
protein synthesis. Here, we discuss how this network is regulated by both
extracellular signals, such as growth factors, and intracellular signals, such
as nutrients. We discuss how mutations amplifying either type of signal can
lead to tumor formation. In particular, we focus on the recent discovery that a
tumor suppressor complex whose function is lost in tuberous sclerosis patients
regulates the nutrient signal carried by the critical signaling protein TOR to
the effectors 4EBP1 and S6K1. Finally, we describe how the small molecule
rapamycin, which inhibits TOR and thereby the activation of these effectors,
could be useful to treat tumors that have become dependent upon this pathway
for growth. N. Ref:: 80
----------------------------------------------------
[2]
TÍTULO / TITLE: - Dendritic cells:
emerging pharmacological targets of immunosuppressive drugs.
REVISTA
/ JOURNAL: - Nat Rev Immunol 2004 Jan;4(1):24-34.
●●
Enlace al texto completo (gratuito o de pago) 1038/nri1256
AUTORES
/ AUTHORS: - Hackstein H; Thomson AW
INSTITUCIÓN
/ INSTITUTION: - Institute for Clinical Immunology and
Transfusion Medicine, Justus-Liebig University Giessen, Langhansstr. 7, D-35392
Giessen, Germany. holger.hackstein@immunologie.med.uni-giessen.de
RESUMEN
/ SUMMARY: - Immunosuppressive drugs have
revolutionized organ transplantation and improved the therapeutic management of
autoimmune diseases. The development of immunosuppressive drugs and
understanding of their action traditionally has been focused on lymphocytes,
but recent evidence indicates that these agents interfere with immune responses
at the earliest stage, targeting key functions of dendritic cells (DCs). Here,
we review our present understanding of how classical and new immunosuppressive
agents interfere with DC development and function. This knowledge might provide
a rational basis for the selection of immunosuppressive drugs in different
clinical settings and for the generation of tolerogenic DCs in the
laboratory. N. Ref:: 116
----------------------------------------------------
[3]
- Castellano -
TÍTULO / TITLE:La ruta de senalizacion
CA++/calcineurina/NFAT en activacion endotelial y angiogenesis: efectos de la
ciclosporina A. CA++/ calcineurin/NFAT signaling in endothelial activation and
angiogenesis: effects od cyclosporin A .
REVISTA
/ JOURNAL: - Nefrologia. Acceso gratuito al texto
completo.
●●
Enlace a la Editora de la Revista http://www.aulamedica.es/nefrologia/
●●
Cita: Nefrologia: <> 2003;23 Suppl 3:44-8.
AUTORES
/ AUTHORS: - Quesada AJ; Redondo JM
INSTITUCIÓN
/ INSTITUTION: - Centro de Biologia Molecular Severo Ochoa,
Consejo Superior de Investigaciones Cientificas, Universidad Autonoma de Madrid
y Centro Nacional de Investigaciones Cardiovasculares (CNIC), Sinesio Delgado,
4 28049 Cantoblanco, Madrid. jmredondo@cbm.uam.es N. Ref:: 31
----------------------------------------------------
[4]
TÍTULO / TITLE: - Identification of TOR
signaling complexes: more TORC for the cell growth engine.
REVISTA
/ JOURNAL: - Cell 2002 Oct 4;111(1):9-12.
AUTORES
/ AUTHORS: - Abraham RT
INSTITUCIÓN
/ INSTITUTION: - Program in Signal Transduction Research,
Cancer Research Center, The Burnham Institute, 10901 North Torrey Pines Road,
La Jolla, CA 92037, USA. abraham@burnham.org
RESUMEN
/ SUMMARY: - The Target of Rapamycin (TOR) proteins
function in signaling pathways that promote protein synthesis and cell growth.
In yeast, TOR signaling is regulated by nutrient availability, whereas in
metazoan cells TOR activities may be controlled by both nutrients and growth
factors. The recent identification of novel TOR-interacting proteins has
provided crucial insights into TOR regulation and function. N. Ref:: 20
----------------------------------------------------
[5]
TÍTULO / TITLE: - Interleukin-2 receptor
monoclonal antibodies in renal transplantation: meta-analysis of randomised
trials.
REVISTA
/ JOURNAL: - British Medical J (BMJ). Acceso gratuito
al texto completo.
●●
Enlace a la Editora de la Revista http://bmj.com/search.dtl
●●
Cita: British Medical J. (BMJ): <> 2003 Apr 12;326(7393):789.
●●
Enlace al texto completo (gratuito o de pago) 1136/bmj.326.7393.789
AUTORES
/ AUTHORS: - Adu D; Cockwell P; Ives NJ; Shaw J;
Wheatley K
INSTITUCIÓN
/ INSTITUTION: - Department of Nephrology, Queen Elizabeth
Hospital, Birmingham, B15 2TH. dwomoa.adu@uhb.nhs.uk
RESUMEN
/ SUMMARY: - OBJECTIVE: To study the effect of
interleukin-2 receptor monoclonal antibodies on acute rejection episodes, graft
loss, deaths, and rate of infection and malignancy in patients with renal
transplants. DESIGN: Meta-analysis of published data. DATA SOURCES: Medline,
Embase, and Cochrane library for years 1996-2003 plus search of medical
editors’ trial amnesty and contact with manufacturers of the antibodies.
SELECTION OF STUDIES: Randomised controlled trials comparing interleukin-2
receptor antibodies with placebo or no additional treatment in patients with
renal transplants receiving ciclosporin based immunosuppression. RESULTS: Eight
randomised controlled trials involving 1871 patients met the selection criteria
(although only 1858 patients were analysed). Interleukin-2 receptor antibodies
significantly reduced the risk of acute rejection (odds ratio 0.51, 95%
confidence interval 0.42 to 0.63). There were no significant differences in the
rate of graft loss (0.78, 0.58 to 1.04), mortality (0.75, 0.46 to 1.23),
overall incidence of infections (0.97, 0.77 to 1.24), incidence of
cytomegalovirus infections (0.81, 0.62 to 1.04), or risk of malignancies at one
year (0.82, 0.39 to 1.70). The different antibodies had a similar sized effect
on acute rejection (test for heterogeneity P=0.7): anti-Tac (0.37, 0.16 to
0.89), BT563 (0.37, 0.1 to 1.38), basiliximab (0.56, 0.44 to 0.72), and
daclizumab (0.46, 0.32 to 0.67). The reduction in acute rejections was similar
for all ciclosporin based immunosuppression regimens (test for heterogeneity
P=1.0). CONCLUSIONS: Adding interleukin-2 receptor antibodies to ciclosporin
based immunosuppression reduces episodes of acute rejection at six months by
49%. There is no evidence of an increased risk of infective complications.
Longer follow up studies are needed to confirm whether interleukin-2 receptor
antibodies improve long term graft and patient survival.
----------------------------------------------------
[6]
TÍTULO / TITLE: - Novel therapeutic
molecular targets for prostate cancer: the mTOR signaling pathway and epidermal
growth factor receptor.
REVISTA
/ JOURNAL: - J Urol 2004 Feb;171(2 Pt 2):S41-3;
discussion S44.
●●
Enlace al texto completo (gratuito o de pago) 1097/01.ju.0000108100.53239.b7
AUTORES
/ AUTHORS: - Tolcher AW
INSTITUCIÓN
/ INSTITUTION: - Director Clinical Research, Institute for
Drug Development Cancer Therapy and Research Center, San Antonio, Texas, USA.
RESUMEN
/ SUMMARY: - PURPOSE: The scientific rationale and
existing evidence for the use of novel molecular targets in the chemoprevention
of cancer are reviewed, with special attention to prostate cancer. MATERIALS
AND METHODS: A search for relevant literature on basic science and clinical
trials was conducted using PubMed/MEDLINE. RESULTS: The emergence of
molecularly targeted therapies for advanced malignancies creates an important
opportunity to examine these agents for the chemoprevention of prostate cancer.
Two critical targets in the proliferation and malignant transformation of
normal cells, the PI3/Akt signal transduction pathway and the epidermal growth
factor receptor, are currently the focus of several novel investigational
therapies that are in late stage phase II and phase III studies. CONCLUSIONS:
Research to date supports consideration of these novel molecular targets as
future agents in the chemoprevention of prostate cancer. N. Ref:: 28
----------------------------------------------------
[7]
TÍTULO / TITLE: - A randomized long-term
trial of tacrolimus/sirolimus versus tacrolimus/mycophenolate mofetil versus
cyclosporine (NEORAL)/sirolimus in renal transplantation. II. Survival,
function, and protocol compliance at 1 year.
REVISTA
/ JOURNAL: - Transplantation 2004 Jan 27;77(2):252-8.
●●
Enlace al texto completo (gratuito o de pago) 1097/01.TP.0000101495.22734.07
AUTORES
/ AUTHORS: - Ciancio G; Burke GW; Gaynor JJ; Mattiazzi
A; Roth D; Kupin W; Nicolas M; Ruiz P; Rosen A; Miller J
INSTITUCIÓN
/ INSTITUTION: - Department of Surgery, Division of
Transplantation, University of Miami School of Medicine, Miami, FL 33101, USA. gciancio@med.miami.edu
RESUMEN
/ SUMMARY: - BACKGROUND: In an attempt to reduce
chronic calcineurin inhibitor induced allograft nephropathy in first cadaver
and human leukocyte antigen non-identical living-donor renal transplantation,
sirolimus (Siro) or mycophenolate mofetil (MMF) was tested as adjunctive
therapy, with planned dose reductions of tacrolimus (Tacro) over the first year
postoperatively. Adjunctive Siro therapy with a similar dose reduction
algorithm for Neoral (Neo) was included for comparison. METHODS: The detailed
dose reduction plan (Tacro and Siro, group A; Tacro and MMF, group B; Neo and
Siro, group C) is described in our companion report in this issue of
Transplantation. The present report documents function, patient and graft
survival, protocol compliance, and adverse events. RESULTS: As mentioned (in
companion report), group demographics were similar. The present study shows no
significant differences in 1-year patient and graft survival but does show a
trend that points to more difficulties in group C by way of a rising slope of
serum creatinine concentration (P=0.02) and decreasing creatinine clearance
(P=0.04). There were more patients who discontinued the protocol plan in group
C. Thus far, no posttransplant lymphomas have appeared, and infectious
complications have not differed among the groups. However, a greater percentage
of patients in group C were placed on antihyperlipidemia therapy, with an
(unexpected) trend toward a higher incidence of posttransplant diabetes
mellitus in this group. Group A required fewer, and group B the fewest,
antihyperlipidemia therapeutic interventions (P<0.00001). CONCLUSIONS: This
1-year interim analysis of a long-term, prospective, randomized
renal-transplant study indicates that decreasing maintenance dosage of Tacro
with adjunctive Siro or MMF appears to point to improved long-term function,
with reasonably few adverse events.
----------------------------------------------------
[8]
TÍTULO / TITLE: - The target of rapamycin
(TOR) proteins.
REVISTA
/ JOURNAL: - Proc Natl Acad Sci U S A. Acceso gratuito
al texto completo a partir de los 6 meses de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.pnas.org/
●●
Cita: Proc Natl Acad Sci USA (PNAS): <> 2001 Jun 19;98(13):7037-44.
●●
Enlace al texto completo (gratuito o de pago) 1073/pnas.121145898
AUTORES
/ AUTHORS: - Raught B; Gingras AC; Sonenberg N
INSTITUCIÓN
/ INSTITUTION: - Department of Biochemistry and McGill
Cancer Centre, McGill University, 3655 Promenade Sir-William-Osler, Montreal,
QC H3G 1Y6 Canada.
RESUMEN
/ SUMMARY: - Rapamycin potently inhibits downstream
signaling from the target of rapamycin (TOR) proteins. These evolutionarily
conserved protein kinases coordinate the balance between protein synthesis and
protein degradation in response to nutrient quality and quantity. The TOR
proteins regulate (i) the initiation and elongation phases of translation, (ii)
ribosome biosynthesis, (iii) amino acid import, (iv) the transcription of
numerous enzymes involved in multiple metabolic pathways, and (v) autophagy.
Intriguingly, recent studies have also suggested that TOR signaling plays a
critical role in brain development, learning, and memory formation. N. Ref:: 132
----------------------------------------------------
[9]
TÍTULO / TITLE: - Regulation of
translation initiation by FRAP/mTOR.
REVISTA
/ JOURNAL: - Genes Dev. Acceso gratuito al texto
completo a partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.genesdev.org/
●●
Cita: Genes & Development: <> 2001 Apr 1;15(7):807-26.
●●
Enlace al texto completo (gratuito o de pago) 1101/gad.887201
AUTORES
/ AUTHORS: - Gingras AC; Raught B; Sonenberg N
INSTITUCIÓN
/ INSTITUTION: - Department of Biochemistry, McGill
University, Montreal, Quebec H3G 1Y6, Canada.
N. Ref:: 236
----------------------------------------------------
[10]
TÍTULO / TITLE: - Rapamycin plays a new
role as differentiator of vascular smooth muscle phenotype. focus on “The
mTOR/p70 S6K1 pathway regulates vascular smooth muscle differentiation”.
REVISTA
/ JOURNAL: - Am J Physiol Cell Physiol. Acceso gratuito
al texto completo.
●●
Enlace a la Editora de la Revista http://ajpcell.physiology.org/contents-by-date.0.shtml
●●
Cita: Am J Physiol Cell Physiol: <> 2004 Mar;286(3):C480-1.
●●
Enlace al texto completo (gratuito o de pago) 1152/ajpcell.00526.2003
AUTORES
/ AUTHORS: - Lucchesi PA N. Ref:: 12
----------------------------------------------------
[11]
TÍTULO / TITLE: - CD3-specific antibody-induced
active tolerance: from bench to bedside.
REVISTA
/ JOURNAL: - Nat Rev Immunol 2003 Feb;3(2):123-32.
●●
Enlace al texto completo (gratuito o de pago) 1038/nri1000
AUTORES
/ AUTHORS: - Chatenoud L
INSTITUCIÓN
/ INSTITUTION: - Centre de l’Association Claude Bernard sur
les Maladies Autoimmunes and Hopital Necker Enfants Malades IRNEM, 161 Rue de
Sevres, 75015 Paris, France. chatenoud@necker.fr
RESUMEN
/ SUMMARY: - Although they were used initially as
non-specific immunosuppressants in transplantation, CD3-specific monoclonal
antibodies have elicited renewed interest owing to their capacity to induce
immune tolerance. In mouse models of autoimmune diabetes, CD3-specific
antibodies induce stable disease remission by restoring tolerance to pancreatic
beta-cells. This phenomenon was extended recently to the clinic—preservation of
beta-cell function in recently diagnosed patients with diabetes was achieved by
short-term administration of a CD3-specific antibody. CD3-specific antibodies
arrest ongoing disease by rapidly clearing pathogenic T cells from the target.
Subsequently, they promote long-term T-cell-mediated active tolerance. Recent
data indicate that transforming growth factor-beta-dependent CD4+CD25+
regulatory T cells might have a central role in this effect. N. Ref:: 117
----------------------------------------------------
[12]
TÍTULO / TITLE: - Neuroimmunophilins:
novel neuroprotective and neuroregenerative targets.
REVISTA
/ JOURNAL: - Ann Neurol 2001 Jul;50(1):6-16.
AUTORES
/ AUTHORS: - Guo X; Dillman JF 3rd; Dawson
VL; Dawson TM
INSTITUCIÓN
/ INSTITUTION: - Department of Neurology, The Johns Hopkins
University School of Medicine, Baltimore, MD 21287, USA.
RESUMEN
/ SUMMARY: - Cyclosporin A (CsA) and FK506 (tacrolimus)
are immunosuppresants that are widely used in organ transplantation. CsA is an
11-member cyclic peptide, whereas FK506 is a macrolide antibiotic. Recently,
these powerful and useful compounds have become of great interest to
neuroscientists for their unique neuroprotective and neuroregenerative effects.
These drugs and nonimmunosuppressive analogs protect neurons from the effects
of glutamate excitotoxicity, focal ischemia, and
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic cell
death. They also stimulate functional recovery of neurons in a variety of
neurologic injury paradigms. These drugs exert their effects via immunophilins,
the protein receptors for these agents. The immunophilin ligands show
particular promise as a novel class of neuroprotective and neuroregenerative
agents that have the potential to treat a variety of neurologic disorders. N. Ref:: 102
----------------------------------------------------
[13]
TÍTULO / TITLE: - New agents in acute
myeloid leukemia and other myeloid disorders.
REVISTA
/ JOURNAL: - Cancer 2004 Feb 1;100(3):441-54.
●●
Enlace al texto completo (gratuito o de pago) 1002/cncr.11935
AUTORES
/ AUTHORS: - Ravandi F; Kantarjian H; Giles F; Cortes J
INSTITUCIÓN
/ INSTITUTION: - Department of Leukemia, The University of
Texas M D Anderson Cancer Center, Houston, Texas 77030, USA. fravandi@mdanderson.org
RESUMEN
/ SUMMARY: - Over the past several decades,
improvements in chemotherapeutic agents and supportive care have resulted in
significant progress in treating patients with acute myeloid leukemia (AML).
More recently, advances in understanding the biology of AML have resulted in
the identification of new therapeutic targets. The success of
all-trans-retinoic acid in acute promyelocytic leukemia and of imatinib
mesylate in chronic myeloid leukemia have demonstrated that targeted therapy
may be more effective and less toxic when well defined targets are available.
At the same time, understanding mechanisms of drug resistance and means to
overcome them has led to modification of some of the existing cytotoxic agents.
Rational design and conduct of clinical trials is necessary to ensure that the
full potential of these new agents is realized. N. Ref:: 140
----------------------------------------------------
[14]
TÍTULO / TITLE: - The transplantation of
hematopoietic stem cells after non-myeloablative conditioning: a cellular
therapeutic approach to hematologic and genetic diseases.
REVISTA
/ JOURNAL: - Immunol Res 2003;28(1):13-24.
AUTORES
/ AUTHORS: - Maris M; Storb R
INSTITUCIÓN
/ INSTITUTION: - Fred Hutchinson Cancer Research Center,
and University of Washington, Seattle, WA, USA. mmaris@fhcrc.org
RESUMEN
/ SUMMARY: - Originally, allogeneic hematopoietic stem
cell transplantation (HSCT) was viewed as a form of rescue from the marrow
lethal effects of high doses of chemo-radiotherapy used to both eradicate
malignancy and to provide sufficient immunosuppression to ensure allogeneic
engraftment. Clear evidence of a therapeutic graft-versus-tumor (GVT) effect
mediated by allogeneic effector cells (T cells) has prompted the exploration of
HSCT regimens that rely solely upon host immunosuppression (non-myeloablative)
to facilitate allogeneic donor engraftment. The engrafted donor effector cells
are then used to accomplish the task of eradicating host malignant cells. The
non-myeloblative regimen developed in Seattle uses 2 Gy total body irradiation
(TBI) before transplant followed by postgrafting cyclosporine (CSP) and
mycophenolate mofetil (MMF). This regimen resulted in initial mixed donor-host
chimerism in all patients with hematologic malignancies and genetic disorders
who received HLA-matched sibling allografts. The 17% incidence of graft
rejection was reduced to 3% with the addition of fludarabine, 30 mg/m2/day on d
-4, -3, and -2. The non-myeloablative combination of fludarabine/TBI has also
been successful at achieving high engraftment rates in recipients of 10 of 10
HLA antigen matched unrelated donor HSCTs in patients with hematologic
malignancies. By reducing acute toxicities relative to conventional HSCT, most
patients have received their pre- and post-HSCT therapy almost exclusively as
outpatients. Acute and chronic GVHD occur after non-myeloablative HSCT, but the
incidence and severity appear less compared to conventional HSCT. As in
conventional transplants, immune dysregulation from GVHD and its treatment and
delayed reconstitution of immune function continue to present risks to patients
who have otherwise undergone successful non-myeloablative HSCT. Cellular
therapeutic effects have been observed after non-myeloablative HSCT such as
correction of inherited genetic disorders, and eradication of hematologic
malignant diseases and renal cell carcinoma via GVT responses. N. Ref:: 52
----------------------------------------------------
[15]
TÍTULO / TITLE: - Drug immunosuppression
therapy for adult heart transplantation. Part 2: clinical applications and
results.
REVISTA
/ JOURNAL: - Ann Thorac Surg 2004 Jan;77(1):363-71.
AUTORES
/ AUTHORS: - Mueller XM
INSTITUCIÓN
/ INSTITUTION: - Department of Cardiovascular Surgery,
Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada. xavier.mueller@usherbrooke.ca
RESUMEN
/ SUMMARY: - This review describes the clinical
application of classical immunosuppressive drugs as well as that of more recent
drugs. All current immunosuppressive drugs target T-cell activation, and
cytokine production and clonal expansion, or both. Immunosuppressive protocols
can be broadly divided into induction therapy, maintenance immunosuppression,
and treatment of acute rejection episodes.
N. Ref:: 82
----------------------------------------------------
[16]
TÍTULO / TITLE: - Treatment of idiopathic
nephrosis by immunophillin modulation.
REVISTA
/ JOURNAL: - Nephrol Dial Transplant. Acceso gratuito
al texto completo a partir de los 2 años de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://ndt.oupjournals.org/
●●
Cita: Nephrology Dialysis Transplantation: <> 2003 Aug;18 Suppl
6:vi79-86.
AUTORES
/ AUTHORS: - Meyrier A
INSTITUCIÓN
/ INSTITUTION: - Service de Nephrologie, Hopital Europeen
Georges Pompidou, 20 rue Leblanc, F-75015 Paris, France. alain.meyrier@brs.ap-hop-paris.fr
RESUMEN
/ SUMMARY: - Until 1985, glucocorticoids and cytotoxic
drugs were the only treatments available for idiopathic nephrotic syndrome
(nephrosis), that is, minimal change disease (MCD) and focal segmental
glomerulosclerosis (FSGS). Trials of cyclosporine (CsA) treatment of nephrosis,
the rationale of which was based on pathophysiologic considerations, have shown
that this immunophillin modulator is effective in inducing and maintaining
remission in patients suffering from idiopathic nephrotic syndrome. It appears
that the best results, in the order of 80% remission rate, are obtained in
steroid-sensitive cases, essentially MCD, and that in steroid-resistant FSGS
the drug obtains remission in no more than 20% of the cases. Addition of
glucocorticoids increases the success rate to approximately 30% of cases. Renal
toxicity is proportional to previous impairment of renal function, primary
renal disease (FSGS vs MCD) dosage >5.5 mg/kg/day and duration of treatment.
The better bioavailability of the new formulation of CsA (Neoral), implies that
the former dosage recommendations be reconsidered for distinctly lower figures.
Repeat renal biopsy after 1 year of continuous CsA treatment is advisable, as
stable serum creatinine levels may be falsely reassuring. CsA dependency is the
rule during the first year of treatment. However, in some 25% of cases stable
remission may be maintained after slow tapering off following 3-4 years of
treatment. Other immunophillin modulators have been tried in the treatment of
idiopathic nephrotic syndrome. Despite few preliminary reports indicating some
success of tacrolimus the effects of this drug do not seem convincingly
superior to CsA in terms of remission rate, toxicity and dependency. Rapamycin
has not been tried in the treatment of nephrosis. Anecdotal cases of de novo
FSGS induced by rapamycin in transplanted patients might indicate that this
drug is in fact contraindicated in the treatment of nephrosis. N. Ref:: 36
----------------------------------------------------
[17]
TÍTULO / TITLE: - In vitro generation of
IL-10-producing regulatory CD4+ T cells is induced by immunosuppressive drugs
and inhibited by Th1- and Th2-inducing cytokines.
REVISTA
/ JOURNAL: - Immunol Lett 2003 Jan 22;85(2):135-9.
AUTORES
/ AUTHORS: - O’Garra A; Barrat FJ
INSTITUCIÓN
/ INSTITUTION: - Division of Immunoregulation, The National
Institute for Medical Research (NIMR), The Ridgeway, Mill Hill, NW7 1AA,
London, UK. N. Ref:: 40
----------------------------------------------------
[18]
TÍTULO / TITLE: - Renal transplantation:
can we reduce calcineurin inhibitor/stop steroids? Evidence based on protocol
biopsy findings.
REVISTA
/ JOURNAL: - J Am Soc Nephrol. Acceso gratuito al texto
completo a partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.jasn.org/
●●
Cita: Journal of the American Society of Nephrology: <> 2003
Mar;14(3):755-66.
AUTORES
/ AUTHORS: - Gotti E; Perico N; Perna A; Gaspari F;
Cattaneo D; Caruso R; Ferrari S; Stucchi N; Marchetti G; Abbate M; Remuzzi G
INSTITUCIÓN
/ INSTITUTION: - Department of Medicine and
Transplantation, Ospedali Riuniti di Bergamo, Mario Negri Institute for
Pharmacological Research, Italy.
RESUMEN
/ SUMMARY: - How to combine antirejection drugs and
which is the optimal dose of steroids and calcineurin inhibitors beyond the
first year after kidney transplantation to maintain adequate immunosuppression
without major side effects are far from clear. Kidney transplant patients on
steroid, cyclosporine (CsA), and azathioprine were randomized to per-protocol
biopsy (n = 30) or no-biopsy (n = 29) 1 to 2 yr posttransplant. Steroid or CsA
were discontinued or reduced on the basis of biopsy to establish effects on
drug-related complications, acute rejection, and graft function over 3 yr of
follow-up. Serum creatinine, GFR (plasma clearance of iohexol), RPF (renal
clearance of p-aminohippurate), CsA pharmacokinetics, and adverse events were
monitored yearly. At the end, patients underwent a second biopsy. Per-protocol
biopsy histology revealed no lesions (n = 5, steroid withdrawal), CsA
nephropathy (n = 13, CsA discontinuation/reduction), or chronic rejection (n =
12, standard therapy). Reducing the drug regimen led to overall fewer side
effects related to immunosuppression as compared with standard therapy or
no-biopsy. Steroids were safely stopped with no acute rejection or graft loss.
Complete CsA discontinuation was associated with acute rejection in the first
four patients. Lowering CsA to low target CsA trough (30 to 70 ng/ml) never led
to acute rejection or major renal function deterioration. Biopsy patients on
conventional regimen had no acute rejection, one graft loss, no significant
change in GFR, and significant RPF decline. No-biopsy controls: no acute
rejection, one graft loss, significant decline of GFR and RPF. By serial biopsy
analysis, severe lesions did not develop in patients with steroid
discontinuation in contrast to patients on standard therapy over follow-up. CsA
reduction did not adversely affect histology. Per-protocol biopsy more than 1
yr after kidney transplantation is a safe procedure to guide change of drug
regimen and to lower the risk of major side effects.
----------------------------------------------------
[19]
TÍTULO / TITLE: - Drug immunosuppression
therapy for adult heart transplantation. Part 1: immune response to allograft
and mechanism of action of immunosuppressants.
REVISTA
/ JOURNAL: - Ann Thorac Surg 2004 Jan;77(1):354-62.
AUTORES
/ AUTHORS: - Mueller XM
INSTITUCIÓN
/ INSTITUTION: - Department of Cardiovascular Surgery,
Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada. xavier.mueller@usherbrooke.ca
RESUMEN
/ SUMMARY: - In the early days of transplantation,
immunosuppression therapy was rather broad and nonspecific, mainly using
high-dose corticosteroids and azathioprine. Thereafter we progressively
narrowed the target of immunosuppressive strategy starting with polyclonal
antibodies. The introduction of cyclosporine, OKT3, and tacrolimus further
narrowed the target on the T-cell pathways. More recently mycophenolate mofetil
progressively took the place of azathioprine with its higher lymphocyte
specificity and sirolimus and interleukin-2 receptor antibodies were
introduced. In this field in constant movement the aim is to find a drug or a
regimen that provides optimal immunosuppression therapy with minimal side
effects, in other words to find the right balance between overimmunosuppression
and underimmunosuppression therapy. This review is divided into two parts. The
first part will provide a basic understanding of the immunologic response to
allograft and explain how conventional and recently introduced immunosuppressive
agents work. The second part will describe the clinical application of
immunosuppressive drugs to provide practical information for those in charge of
heart transplant recipients. N.
Ref:: 68
----------------------------------------------------
[20]
TÍTULO / TITLE: - Mammalian target of
rapamycin inhibition as therapy for hematologic malignancies.
REVISTA
/ JOURNAL: - Cancer 2004 Feb 15;100(4):657-66.
●●
Enlace al texto completo (gratuito o de pago) 1002/cncr.20026
AUTORES
/ AUTHORS: - Panwalkar A; Verstovsek S; Giles FJ
INSTITUCIÓN
/ INSTITUTION: - Section of Developmental Therapeutics,
Department of Leukemia, University of Texas M. D. Anderson Cancer Center,
Houston, Texas, USA.
RESUMEN
/ SUMMARY: - The mammalian target of rapamycin (mTOR)
is a downstream effector of the phosphatidylinositol 3-kinase (PI3K)/Akt
(protein kinase B) signaling pathway, which mediates cell survival and
proliferation. mTOR regulates essential signal-transduction pathways, is
involved in the coupling of growth stimuli with cell cycle progression, and
initiates mRNA translation in response to favorable nutrient environments. mTOR
is involved in regulating many aspects of cell growth, including membrane
traffic, protein degradation, protein kinase C signaling, ribosome biogenesis,
and transcription. Because mTOR activates both the 40S ribosomal protein S6
kinase (p70s6k) and the eukaryotic initiation factor 4E-binding protein 1, its
inhibitors cause G1-phase cell cycle arrest. Inhibitors of mTOR also prevent
cyclin dependent kinase (CDK) activation, inhibit retinoblastoma protein
phosphorylation, and accelerate the turnover of cyclin D1, leading to a
deficiency of active CDK4/cyclin D1 complexes, all of which may help cause
G1-phase arrest. It is known that the phosphatase and tensin homologue tumor
suppressor gene (PTEN) plays a major role in embryonic development, cell
migration, and apoptosis. Malignancies with PTEN mutations, which are
associated with constitutive activation of the PI3K/Akt pathway, are relatively
resistant to apoptosis and may be particularly sensitive to mTOR inhibitors.
Rapamycin analogs with relatively favorable pharmaceutical properties,
including CCI-779, RAD001, and AP23573, are under investigation in patients
with hematologic malignancies. N.
Ref:: 116
----------------------------------------------------
[21]
TÍTULO / TITLE: - Cholesteryl ester
transfer protein facilitates the movement of water-insoluble drugs between
lipoproteins: a novel biological function for a well-characterized lipid
transfer protein.
REVISTA
/ JOURNAL: - Biochem Pharmacol 2002 Dec
15;64(12):1669-75.
AUTORES
/ AUTHORS: - Kwong M; Wasan KM
INSTITUCIÓN
/ INSTITUTION: - Division of Pharmaceutics and
Biopharmaceutics, Faculty of Pharmaceutical Sciences, The University of British
Columbia, 2146 East Mall Avenue, Vancouver, BC, Canada V6T 1Z3.
RESUMEN
/ SUMMARY: - This review article addresses the recently
discovered finding that cholesteryl ester transfer protein (CETP) can
facilitate the transfer of water-insoluble drugs between different lipoprotein
subclasses. This protein, which is often referred to as lipid transfer protein
I (LTP I), is involved in the lipid regulation of lipoproteins. It is
responsible for the facilitated transfer of core lipoprotein lipids,
cholesteryl ester and triglycerides, and approximately one-third of the coat
lipoprotein lipid, phosphatidylcholine, between different plasma lipoproteins.
The human body appears to recognize exogenous water-insoluble drugs as
lipid-like particles, which suggests that these compounds may interact with
lipoproteins just like endogenous plasma lipids, and thus their transfer
between lipoproteins may be facilitated by plasma CETP. Patients with a variety
of diseases (i.e. diabetes, cancer, AIDS) often exhibit hypo- and/or
hypercholesterolemia and triglyceridemia, commonly referred to as
dyslipidemias, which result in changes in their plasma lipoprotein-lipid
composition and concentration. The interaction of water-insoluble drugs with
these dyslipidemic lipoproteins may be responsible for the differences seen in
the pharmacokinetics and pharmacodynamics of the drug within different diseased
patient populations. It is possible that these differences may be linked to the
ability of CETP to transfer these compounds from one lipoprotein to another.
This review examines the current understanding of the relationship between CETP
activity and the lipoprotein distribution of a number of compounds (e.g.
amphotericin B and cyclosporine A). It further suggests that additional
research will expand our understanding of the role of CETP to explain other
functions in lipophilic drug distribution and metabolism. N. Ref:: 45
----------------------------------------------------
[22]
TÍTULO / TITLE: - Advances in
transplantation tolerance.
REVISTA
/ JOURNAL: - Lancet 2001 Jun 16;357(9272):1959-63.
AUTORES
/ AUTHORS: - Yu X; Carpenter P; Anasetti C
INSTITUCIÓN
/ INSTITUTION: - Human Immunogenetics Program, Fred
Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
RESUMEN
/ SUMMARY: - Immunosuppressive drugs developed in the
past two decades have improved the short-term survival of organ allografts, but
tolerance has not been achieved and almost all transplant recipients continue
to require drugs throughout life. Graft rejection arises from the cognate
interaction of T cells with antigen-presenting cells, the recognition of
alloantigen through the T-cell receptor, and the delivery of accessory
stimulation signals. Once activated by the specific antigen, replicating T
cells die if they are re-exposed to the same antigen. Since depletion of
antigen-activated T cells is one critical mechanism of transplantation
tolerance, drugs such as ciclosporin that interfere with activation-induced
T-cell death could inhibit tolerance, whereas drugs such as mycophenolate
mofetil, that induce the death of activated T cells, could facilitate
tolerance. Other tolerance mechanisms depend on inactivation rather than
elimination of allograft reactive T cells. When antigen recognition occurs
without costimulation through the CD28 and CD154 accessory receptors, or in
absence of cell division, T cells become unresponsive. Thus, inhibitors of CD28
and CD154, and inhibition of T-cell division by rapamycin promotes
transplantation tolerance. N.
Ref:: 54
----------------------------------------------------
[23]
TÍTULO / TITLE: - Rational use of new and
existing disease-modifying agents in rheumatoid arthritis.
REVISTA
/ JOURNAL: - Ann Intern Med. Acceso gratuito al texto
completo a partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.annals.org/
●●
Cita: Annals of Internal Medicine: <> 2001 Apr 17;134(8):695-706.
AUTORES
/ AUTHORS: - Kremer JM
INSTITUCIÓN
/ INSTITUTION: - The Center for Rheumatology, Albany, New
York, USA. jkremer@rheum-docs.com
RESUMEN
/ SUMMARY: - Because of radiographic evidence of
progressive bone loss and the inability to eliminate synovial proliferation
with methotrexate, it became apparent that therapy for rheumatoid arthritis
needed further advancement. Methotrexate is not a remission-inducing drug and
may have dose-limiting toxicity. In the past 2 years, three new
disease-modifying antirheumatic drugs (DMARDs) have been approved: leflunomide,
etanercept, and infliximab. Each of these agents has demonstrated efficacy
compared with placebo in randomized, controlled studies. Because methotrexate
had a dominant therapeutic role, the new drugs were also studied in combination
with it. Other established DMARDs, such as sulfasalazine and
hydroxychloroquine, have also demonstrated efficacy when used together with
methotrexate. The results of these combination studies clearly demonstrate that
clinical responses can be meaningfully improved when new and existing DMARDs
are added to methotrexate. Although toxicity remains a serious concern when
powerful immune modulators and antimetabolites are used in combination, relatively
few serious adverse events have been reported during 2-year treatment periods.
It has also become apparent that combinations of new DMARDs and methotrexate
virtually halt radiographic progression over 2 years. The new agents are
expensive, but annual costs must be weighed against the personal and societal
expense of joint arthroplasty, hospitalizations, disability, and diminished
quality of life that accompanies poorly controlled rheumatoid arthritis. The
ultimate value of combination DMARD therapy with methotrexate will be
determined by long-term data on safety, efficacy, and effects on radiographic
deterioration of bone. Additional long-term observational data on the incidence
of joint arthroplasty and disability will help to place the issue of societal
costs in a better perspective. This will allow the value of aggressive
treatment to be established with certainty.
N. Ref:: 87
----------------------------------------------------
[24]
TÍTULO / TITLE: - Clinical development of
mammalian target of rapamycin inhibitors.
REVISTA
/ JOURNAL: - Hematol Oncol Clin North Am 2002
Oct;16(5):1101-14.
AUTORES
/ AUTHORS: - Dancey JE
INSTITUCIÓN
/ INSTITUTION: - Cancer Treatment Evaluation Program,
Division of Cancer Treatment and Diagnosis, Investigational Drug
Branch/CTEP/DCTD/NCI, 6130 Executive Boulevard, EPN 7131, Rockville, MD 20854,
USA. danceyj@ctep.nci.nih.gov
RESUMEN
/ SUMMARY: - Rapamycin and CCI-779 have significant in
vitro and in vivo anti-proliferative activity against a broad range of human
tumor cell lines, justifying the clinical evaluation of this class of agent in
cancer patients. Preliminary results from phase I studies of CCI-779 suggest
that the agent is well tolerated and has anti-tumor activity. The challenge to
investigators is to efficiently determine what role this class of agent will
play in the treatment of cancer patients.
N. Ref:: 69
----------------------------------------------------
[25]
TÍTULO / TITLE: - Treatment of nephrotic
syndrome in children and controlled trials.
REVISTA
/ JOURNAL: - Nephrol Dial Transplant. Acceso gratuito
al texto completo a partir de los 2 años de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://ndt.oupjournals.org/
●●
Cita: Nephrology Dialysis Transplantation: <> 2003 Aug;18 Suppl 6:vi75-8.
AUTORES
/ AUTHORS: - Filler G
INSTITUCIÓN
/ INSTITUTION: - Department of Paediatrics, Division of
Nephrology, Children’s Hospital of Eastern Ontario, University of Ottawa,
Canada. filler@cheo.on.ca
RESUMEN
/ SUMMARY: - AIM: To determine the sequential therapy
of childhood nephrotic syndrome (NS) with presumed minimal change nephropathy
using the evidence from clinical trials. METHODS: Meta-analysis of 22
randomized controlled trials was performed, using frequency of relapse and side
effects of therapeutic regimes. RESULTS: A meta-analysis of seven trials
comparing duration of therapy for initial onset showed that duration of at
least 3 months significantly reduced the risk of relapse at 12-24 months
(relative risk 0.73; 95% confidence interval 0.60-0.89) without an increase in adverse
events. Five trials were performed for steroid treatment of relapse.
Deflazacort reduced relapses during therapy, but is not generally available. No
difference was observed when comparing single and divided dosing of prednisone.
Frequency of relapses could not be influenced by duration of relapse therapy.
Alternate day therapy was more effective than intermittent use of prednisone.
Two studies out of five on cyclophosphamide or chlorambucil showed consistently
that alkylating agents should be used before cyclosporine as alternative
therapy to steroids. CONCLUSIONS: Children with initial onset of NS should be
treated with prednisone at a dose of 60 mg/m(2)/day for 6 weeks, followed by a
dose of 40 mg/m(2)/48 h for at least another 6 weeks. If steroid toxicity for
treatment of relapsing NS requires alternative treatment, cyclophosphamide (2
mg/kg/day for at least 8 weeks) remains the drug of choice with a curative
potential. If children still relapse after alkylating agents, levamisole may
serve as an alternative only for frequent relapsing NS, whereas
steroid-dependent NS should be treated with cyclosporine.
----------------------------------------------------
[26]
TÍTULO / TITLE: - Effects of
immunosuppressive drugs on dendritic cells and tolerance induction.
REVISTA
/ JOURNAL: - Transplantation 2003 May 15;75(9
Suppl):37S-42S.
●●
Enlace al texto completo (gratuito o de pago) 1097/01.TP.0000067950.90241.1D
AUTORES
/ AUTHORS: - Lagaraine C; Lebranchu Y
INSTITUCIÓN
/ INSTITUTION: - EA 3249, Cellules hematopoietiques,
hemostase et greffe, Laboratoire d’immunologie, Faculte de medecine, Tours,
France.
RESUMEN
/ SUMMARY: - Dendritic cells, the most effective
antigen-presenting cells for priming naive T cells and initiating immune
responses, are also able to induce tolerance. This balance between immunity and
tolerance depends on the functional stage of dendritic cells (DC). Activation
of naive T cells by immature DC can induce tolerance. It is therefore of
interest to summarize the effects of immunosuppressive agents on DC maturation
and functions. In contrast to glucocorticosteroids, mycophenolate mofetil, and
vitamin D(3) analogs, calcineurin inhibitors do not seem to inhibit DC maturation
in in vitro culture systems. However, these molecules all appear to interfere
with DC functions. N.
Ref:: 44
----------------------------------------------------
[27]
TÍTULO / TITLE: - Donor-specific
tolerance in fully major histocompatibility major histocompatibility
complex-mismatched limb allograft transplants under an anti-alphabeta T-cell
receptor monoclonal antibody and cyclosporine A protocol.
REVISTA
/ JOURNAL: - Transplantation 2003 Dec 27;76(12):1662-8.
●●
Enlace al texto completo (gratuito o de pago) 1097/01.TP.0000105343.49626.6F
AUTORES
/ AUTHORS: - Siemionow MZ; Izycki DM; Zielinski M
INSTITUCIÓN
/ INSTITUTION: - Department of Plastic Surgery, Cleveland
Clinic Foundation, A60, 9500 Euclid Avenue, Cleveland, OH 44195, USA. siemiom@ccf.org
RESUMEN
/ SUMMARY: - BACKGROUND: Recent studies have
demonstrated that treatment with alphabeta-T-cell receptor (TCR) monoclonal
antibody and cyclosporine A (CsA) can extend survival in composite tissue
allografts (CTA). The purpose of this study was to induce tolerance in fully
major histocompatibility complex (MHC)-mismatched rat limb allografts under 7
days of a combined alphabeta-TCR-CsA protocol. METHODS: The authors performed
30 hind-limb allotransplantations across the MHC barrier between Brown Norway
donors (BN; RT1n) and Lewis recipients (LEW; RT1l). Isograft and allograft
controls received no treatment. The experimental groups received monotherapy of
alphabeta-TCR and CsA or a combination of alphabeta-TCR and CsA for 7 days
only. Donor-specific tolerance and immunocompetence were determined by standard
skin grafting in vivo and mixed lymphocyte reaction (MLR) in vitro. The
efficacy of immunosuppressive therapy and the level of donor-specific chimerism
were determined by flow cytometry. RESULTS: Long-term survival (>350 days)
was achieved in allograft recipients (n=6) under the 7-day protocol of combined
alphabeta-TCR-CsA. Donor-specific tolerance and immunocompetence of long-term
chimeras were confirmed by acceptance of skin grafts from the donors and
rejection of the third-party alloantigens (AxC Irish). At day 120, MLR
demonstrated unresponsiveness to the host and donor antigens but strong
reactivity against third-party alloantigens. Flow cytometry confirmed the high
efficacy of immunosuppressive treatment and the development of donor-specific
chimerism (7.6% of CD4+-RT1n+ cells, 1.3% of CD8+-RT1n+ cells, and 16.5% of
CD45RA+-RT1n+ cells) in the periphery of tolerated recipients. CONCLUSIONS:
Combined therapy of alphabeta-TCR-CsA for 7 days resulted in tolerance
induction in fully MHC-mismatched rat hind-limb allografts. Tolerance was
directly associated with stable, donor-specific chimerism.
----------------------------------------------------
[28]
TÍTULO / TITLE: - Dimerizer-regulated
gene expression.
REVISTA
/ JOURNAL: - Curr Opin Biotechnol 2002
Oct;13(5):459-67.
AUTORES
/ AUTHORS: - Pollock R; Clackson T
INSTITUCIÓN
/ INSTITUTION: - ARIAD Gene Therapeutics, 26 Landsdowne
Street, Cambridge, MA 02139, USA. roy.pollock@ariad.com
RESUMEN
/ SUMMARY: - Control of gene expression using small
molecules is a powerful research tool and has clinical utility in the context
of regulated gene therapy. Use of chemical inducers of dimerization, or
dimerizers, for this purpose has several advantages, including tight
regulation, modularity to facilitate iterative improvements, and assembly from
human proteins to minimize immune responses in clinical applications. Recent
developments include the use of the rapamycin-based dimerizer system to
regulate the expression of endogenous genes, the generation of new chemical
dimerizers based on FK506, dexamethasone and methotrexate, and progress towards
the clinical use of adeno-associated virus and adenovirus vectors regulated by
rapamycin analogs. N.
Ref:: 40
----------------------------------------------------
[29]
TÍTULO / TITLE: - The fission yeast TOR
proteins and the rapamycin response: an unexpected tale.
REVISTA
/ JOURNAL: - Curr Top Microbiol Immunol 2004;279:85-95.
AUTORES
/ AUTHORS: - Weisman R
INSTITUCIÓN
/ INSTITUTION: - Department of Molecular Microbiology and
Biotechnology, Faculty of Life Sciences, Tel-Aviv University, 69978 Tel-Aviv,
Israel. ronitt@post.tau.ac.il
RESUMEN
/ SUMMARY: - The TOR proteins are known as key
regulators of cell growth in response to nutritional and mitogenic signals and as
targets for the immunosuppressive and anti-cancerous drug rapamycin. The
fission yeast Schizosaccharomyces pombe has two TOR homologues, tor1+ and
tor2+. Despite their structural similarity, these genes have distinct
functions: tor1+ is required under starvation, extreme temperatures, and
osmotic or oxidative stress conditions, whereas tor2+ is required under normal
growth conditions. Surprisingly, rapamycin does not seem to inhibit the S.
pombe TOR-related functions. Rapamycin specifically inhibits sexual development
in S. pombe, and this seems to stem from direct inhibition of the S. pombe
FKBP12 homologue. Why S. pombe cells are resistant to rapamycin during the
growth phase is as yet unclear and awaits further analysis of the TOR-dependent
signaling pathways. N.
Ref:: 27
----------------------------------------------------
[30]
TÍTULO / TITLE: - Renal function as a
predictor of long-term graft survival in renal transplant patients.
REVISTA
/ JOURNAL: - Nephrol Dial Transplant. Acceso gratuito
al texto completo a partir de los 2 años de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://ndt.oupjournals.org/
●●
Cita: Nephrology Dialysis Transplantation: <> 2003 May;18 Suppl 1:i3-6.
AUTORES
/ AUTHORS: - First MR
INSTITUCIÓN
/ INSTITUTION: - Research and Development, Fujisawa
Healthcare, Inc., Deerfield, IL 60015, USA. roy_first@fujisawa.com
RESUMEN
/ SUMMARY: - Acute rejection is a major risk factor for
kidney graft failure. However, as acute rejection has been progressively
reduced by recent immunosuppressive regimens, other risk factors are becoming
increasingly important. Evidence is accumulating that early renal function
predicts long-term outcome. A recent registry survey of more than 100 000
kidney transplants found that 6- and 12-month serum creatinine levels, as well
as the change between 6 and 12 months, are strongly associated with long-term
graft survival. A survey of paediatric renal transplant recipients showed that
poor creatinine clearance (<50 ml/min) as early as 30 days post-transplant
predicted an annual rate of graft loss of 13% compared with <3% in patients
with 30-day clearance >50 ml/min. This association between early renal
function and long-term outcome was confirmed in multicentre studies. Renal
transplant recipients (n=572) with 6-month serum creatinine levels >1.5
mg/dl suffered 3-year graft loss of 19.3% compared with only 8.5% in patients
with levels <1.6 mg/dl (P<0.001). Significantly fewer patients receiving
tacrolimus had 12-month serum creatinine levels >1.5 mg/dl compared with
cyclosporin (42 versus 54%, P<0.05). Interestingly, a single-centre study
(n=436) found that while glomerular filtration rate (GFR) at 6 months
post-transplant had remained stable over the last decade, the rate of loss of
renal function had decreased. A lower rate of GFR loss was associated with
absence of rejection, use of mycophenolate mofetil rather than azathioprine and
use of tacrolimus rather than cyclosporin (P<0.01). In conclusion, early
measures of renal function allow identification of those patients at highest
risk of graft failure and provide an invaluable tool for improving outcomes by
tailored immunosuppression. The choice of such immunosuppression should be
guided not only by its ability to prevent rejection, but also by its impact on
renal function. N.
Ref:: 11
----------------------------------------------------
[31]
TÍTULO / TITLE: - Composite tissue
allotransplantation in chimeric hosts part II. A clinically relevant protocol
to induce tolerance in a rat model.
REVISTA
/ JOURNAL: - Transplantation 2003 Dec
15;76(11):1548-55.
●●
Enlace al texto completo (gratuito o de pago) 1097/01.TP.0000085288.12571.65
AUTORES
/ AUTHORS: - Prabhune KA; Gorantla VS; Perez-Abadia G;
Francois CG; Vossen M; Laurentin-Perez LA; Breidenbach WC; Wang GG; Anderson
GL; Pidwell DJ; Barker JH; Maldonado C
INSTITUCIÓN
/ INSTITUTION: - Division of Plastic and Reconstructive
Surgery, University of Louisville, Louisville, Kentucky, USA.
RESUMEN
/ SUMMARY: - BACKGROUND: We and others have shown that
mixed allogeneic chimerism induces donor-specific tolerance to composite tissue
allografts across major histocompatibility complex barriers without the need
for immunosuppression. However, a delay period between bone marrow
transplantation and limb allotransplantation is required, making such protocols
impractical for clinical application. This study eliminates this delay period
in a rat hind limb allotransplantation model by performing mixed allogeneic
chimerism induction and transplantation “simultaneously.” METHODS: Group 1
included controls in which naive Wistar Furth (WF) hosts received ACI hind
limbs. Group 2 included (ACI-->WF) chimeras that received limbs from
third-party donors (Fisher), and group 3 included chimeras that received irradiated
(1,050 cGy) ACI limbs. In group 4, WF hosts conditioned with 950 cGy received
irradiated (1,050 cGy) ACI limbs followed by infusion of 100 x 10(6) ACI
T-cell-depleted bone marrow cells and immunotherapy (tacrolimus and
mycophenolate mofetil) for 28 days. Group 5 animals received the same treatment
as group 4 animals without immunotherapy. RESULTS: The rats in groups 1 and 2
rejected their limbs within 10 days. Only one rat in group 4 survived to the
end of the study. Groups 3 and 5 demonstrated long-term limb survival without
rejection or graft-versus-host disease. High levels of donor chimerism
(>80%) were achieved and maintained throughout the study. Mixed lymphocyte
reaction assays in both groups revealed donor-specific hyporesponsiveness with vigorous
third-party reactivity. CONCLUSIONS: This study demonstrated that infusion of
donor bone marrow cells into conditioned hosts immediately after limb
transplantation results in stable mixed chimerism, robust tolerance, and
reliable limb allograft survival.
----------------------------------------------------
[32]
TÍTULO / TITLE: - Tacrolimus ointment for
the treatment of atopic dermatitis: clinical and pharmacologic effects.
REVISTA
/ JOURNAL: - Allergy Asthma Proc 2002
May-Jun;23(3):191-7.
AUTORES
/ AUTHORS: - Rico MJ; Lawrence I
INSTITUCIÓN
/ INSTITUTION: - Fujisawa Healthcare, Inc, 3 Pookway North
Deerfeild, IL 60022, USA.
RESUMEN
/ SUMMARY: - The topical immunomodulator tacrolimus
ointment has been shown to be safe and effective in the treatment of atopic
dermatitis in clinical trials involving over 16,000 patients. Clinical trial
results focusing on tacrolimus’ safety and efficacy are summarized. Minimal
systemic absorption results from topical application in patients with atopic
dermatitis. Although the exact mechanism of action of tacrolimus ointment in
atopic dermatitis is unknown, tacrolimus is known to inhibit up-regulation of
cytokine production following T cell activation and to decrease Fc epsilon RI
expression on dendritic antigen-presenting cells in skin. Additional mechanisms
of action of tacrolimus relevant in the pathogenesis of inflammatory skin
disorders are discussed. N.
Ref:: 27
----------------------------------------------------
[33]
TÍTULO / TITLE: - mTOR as a positive
regulator of tumor cell responses to hypoxia.
REVISTA
/ JOURNAL: - Curr Top Microbiol Immunol
2004;279:299-319.
AUTORES
/ AUTHORS: - Abraham RT
INSTITUCIÓN
/ INSTITUTION: - Program in Signal Transduction Research,
The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA. abraham@burnham.org
RESUMEN
/ SUMMARY: - Rapamycin is a clinically approved
immunosuppressive agent that has recently shown promising antitumor activities
in human patients. In contrast to many conventional chemotherapeutic agents,
rapamycin displays a remarkably high level of selectivity for certain types of
tumors. The pharmacological activities of rapamycin are attributable to the
functional inhibition of a single target protein, termed the mammalian target
of rapamycin (mTOR). Because mTOR is widely expressed in both normal and
transformed cells, variations in mTOR expression levels are likely not a
primary determinant of tumor sensitivity to rapamycin. However, recent studies
highlighted an intriguing link between cancer cell sensitivity to rapamycin and
deregulated signaling through the phosphoinositide (PI) 3-kinase pathway. These
findings have prompted a search for cancer-related responses that are jointly
regulated by the PI 3-kinase signaling cascade and mTOR. The oxygen-regulated
transcription factor, hypoxia-induced factor (HIF)-1, has emerged as a
candidate target for both of these two highly interactive signaling proteins.
Here we review evidence that mTOR functions as a positive regulator of
HIF-1-dependent responses to hypoxic stress in human cancer cells. N. Ref:: 71
----------------------------------------------------
[34]
TÍTULO / TITLE: - TGF-beta expression in
protocol transplant liver biopsies: a comparative study between cyclosporine-A
(CyA) and tacrolimus (FK 506) immunosuppression.
REVISTA
/ JOURNAL: - Transplant Proc 2001
Feb-Mar;33(1-2):1378-80.
AUTORES
/ AUTHORS: - Mohamed MA; Burt AD; Robertson H; Kirby
JA; Talbot D
INSTITUCIÓN
/ INSTITUTION: - Transplant Immunobiology Group, Department
of Surgery, University of Newcastle, NE2 4HH, Newcastle Upon Tyne, UK.
----------------------------------------------------
[35]
TÍTULO / TITLE: - CD30+ T-cell lymphoma
in a patient with psoriasis treated with ciclosporin and infliximab.
REVISTA
/ JOURNAL: - Br J Dermatol 2003 Jul;149(1):170-3.
AUTORES
/ AUTHORS: - Mahe E; Descamps V; Grossin M; Fraitag S;
Crickx B
INSTITUCIÓN
/ INSTITUTION: - Department of Dermatology, Bichat-Claude
Bernard Hospital, 46 Rue Henri-Huchard, Paris Cedex 18, France. emmanuel.mahe@bch.ap-hop-paris.fr
RESUMEN
/ SUMMARY: - There is a known relationship between the
use of immunosuppressive therapies and the development of lymphoproliferative
malignancies. These lymphomas are mainly B-cell nonHodgkin’s lymphomas
associated with Epstein-Barr virus. Most cases concern classical
immunosuppressive treatments including ciclosporin and methotrexate. A
relationship between the new antitumour necrosis factor (TNF)-alpha agents and
lymphoproliferative malignancies is debated. Patients with psoriasis on
immunosuppressive therapies, mainly ciclosporin, are considered to have a low
risk of developing lymphoid proliferation. We report a patient with
erythrodermic psoriasis treated with ciclosporin and infliximab who developed a
CD30+ T-cell lymphoma. This lymphoma regressed after stopping these treatments.
In this case, the anti-TNF-alpha agent may have played a role in association
with ciclosporin in the development of the lymphoproliferative disorder.
Whereas the combination of anti-TNF-alpha therapies with methotrexate has been
well studied, their combination with ciclosporin has been evaluated only in a
few patients. Psoriatic patients who may require anti-TNF-alpha treatment have
often been or will be treated with ciclosporin. The combination of ciclosporin
and anti-TNF-alpha warrants further investigation. N. Ref:: 17
----------------------------------------------------
[36]
TÍTULO / TITLE: - Elucidating TOR
signaling and rapamycin action: lessons from Saccharomyces cerevisiae.
REVISTA
/ JOURNAL: - Microbiol Mol Biol Rev. - Acceso gratuito
al texto completo a partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://mmbr.asm.org/
●●
Cita: Microbiology & Molecular Biology Reviews: <> 2002
Dec;66(4):579-91, table of contents.
AUTORES
/ AUTHORS: - Crespo JL; Hall MN
INSTITUCIÓN
/ INSTITUTION: - Division of Biochemistry, Biozentrum,
University of Basel, CH-4056 Basel, Switzerland.
RESUMEN
/ SUMMARY: - TOR (target of rapamycin) is a
phosphatidylinositol kinase-related protein kinase that controls cell growth in
response to nutrients. Rapamycin is an immunosuppressive and anticancer drug
that acts by inhibiting TOR. The modes of action of TOR and rapamycin are
remarkably conserved from S. cerevisiae to humans. The current understanding of
TOR and rapamycin is derived largely from studies with S. cerevisiae. In this
review, we discuss the contributions made by S. cerevisiae to understanding
rapamycin action and TOR function. N.
Ref:: 171
----------------------------------------------------
[37]
TÍTULO / TITLE: - Structures of
calcineurin and its complexes with immunophilins-immunosuppressants.
REVISTA
/ JOURNAL: - Biochem Biophys Res Commun 2003 Nov
28;311(4):1095-102.
AUTORES
/ AUTHORS: - Ke H; Huai Q
INSTITUCIÓN
/ INSTITUTION: - Department of Biochemistry and Biophysics
and Lineberger Comprehensive Cancer Center, The University of North Carolina,
Chapel Hill, NC 27599-7260, USA. hke@med.unc.edu
RESUMEN
/ SUMMARY: - Calcineurin (CN) is a
Ca(2+)/calmodulin-dependent serine/threonine protein phosphatase and is
involved in many physiological processes such as T-cell activation and cardiac
hypertrophy. The crystal structures of CN and its complexes with FKBP12-FK506
and cyclophilin-cyclosporin showed that the two structurally unrelated
immunophilins-immunosuppressants bind to a common composite surface made up of
the residues from both catalytic subunit and regulatory subunit of CN. The
recognition of the immunophilins and immunosuppressive drugs is achieved by
common but few distinct CN residues. However, the binding pattern of
FKBP12-FK506 such as hydrogen bonding is significantly different from that of
CyPA-CsA. This common but distinct recognition may indicate capacity of the
composition surface for binding of other inhibitory proteins. The recognition
site and the active site are adjacent and form an “L” shaped cleft. This
implies that the immunophilin recognition site may also serve as a recognition
site to define the narrow substrate specificity of calcineurin. N. Ref:: 61
----------------------------------------------------
[38]
TÍTULO / TITLE: - European best practice
guidelines for renal transplantation. Section IV: Long-term management of the
transplant recipient. IV.3.2. Long-term immunosuppression. Therapy conversion.
REVISTA
/ JOURNAL: - Nephrol Dial Transplant. Acceso gratuito
al texto completo a partir de los 2 años de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://ndt.oupjournals.org/
●●
Cita: Nephrology Dialysis Transplantation: <> 2002;17 Suppl 4:20-1.
RESUMEN
/ SUMMARY: - GUIDELINE: Conversion of immunosuppressive
drug therapy is recommended to avoid or reduce drug-specific adverse effects,
and is generally safe for long-term graft outcome.
----------------------------------------------------
[39]
TÍTULO / TITLE: - Multidrug resistance
reversal agents.
REVISTA
/ JOURNAL: - J Med Chem 2003 Nov 6;46(23):4805-17.
●●
Enlace al texto completo (gratuito o de pago) 1021/jm030183a
AUTORES
/ AUTHORS: - Robert J; Jarry C
INSTITUCIÓN
/ INSTITUTION: - Institut Bergonie, 229, Cours de
l’Argonne, 33076 Bordeaux Cedex, France. robert@bergonie.org N. Ref:: 151
----------------------------------------------------
[40]
TÍTULO / TITLE: - Prevention by dietary
(n-6) polyunsaturated phosphatidylcholines of intrahepatic cholestasis induced
by cyclosporine A in animals.
REVISTA
/ JOURNAL: - Life Sci 2003 Jun 13;73(4):381-92.
AUTORES
/ AUTHORS: - Chanussot F; Benkoel L
INSTITUCIÓN
/ INSTITUTION: - INSERM U. 476, Faculte de Medecine, 27 bd
Jean Moulin, 13385 Marseille cedex 05, France. Francoise.Chanussot@medecine.univ-mrs.fr
RESUMEN
/ SUMMARY: - Previous findings showed that dietary
(n-6) polyunsaturated phosphatidylcholines (vegetable lecithin) could
efficiently prevent intrahepatic cholestasis induced by cyclosporine A in rats.
Mechanistic studies showed that expressions in rat liver of Na(+), K(+)-ATPase,
Ca(2+), Mg(2+)-ATPase and F-actin were both decreased by drug administration
and both enhanced by (n-6) lecithin enriched diet. There is a possible direct
effect of phosphatidylcholines, vectors of polyunsaturated fatty acids provided
by the metabolism of the dietary lecithin, on the aforesaid hepatic parameters.
Such modulations by drug and diet result in reversed modifications of membrane
composition and fluidity. Final outcome is decreased and enhanced bile lipid
secretion by cyclosporine and vegetable lecithin enriched diet respectively.
Moreover, we advance the hypothesis of a bypass process including a separate and
functional actin-independent way for the non micellar and
phospholipid-dependent secretion of bile lipids. The relationships between the
ATPases, the microfilament components such as F-actin and the different
transporters still remain to be clarified. Furthermore, one can speculate on
beneficial effects in humans of diets enriched in vegetable lecithins that
might prevent cholestasis induced by cyclosporine A. N. Ref:: 75
----------------------------------------------------
[41]
TÍTULO / TITLE: - Calcineurin
inhibitor-free CD28 blockade-based protocol protects allogeneic islets in
nonhuman primates.
REVISTA
/ JOURNAL: - Diabetes. Acceso gratuito al texto
completo a partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://diabetes.diabetesjournals.org/
●●
Cita: Diabetes: <> 2002 Feb;51(2):265-70.
AUTORES
/ AUTHORS: - Adams AB; Shirasugi N; Durham MM; Strobert
E; Anderson D; Rees P; Cowan S; Xu H; Blinder Y; Cheung M; Hollenbaugh D;
Kenyon NS; Pearson TC; Larsen CP
INSTITUCIÓN
/ INSTITUTION: - Emory Transplant Center, Department of
Surgery, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
RESUMEN
/ SUMMARY: - Recent success using a steroid-free immunosuppressive
regimen has renewed enthusiasm for the use of islet transplantation to treat
diabetes. Toxicities associated with the continued use of a calcineurin
inhibitor may limit the wide-spread application of this therapy. Biological
agents that block key T-cell costimulatory signals, in particular the CD28
pathway, have demonstrated extraordinary promise in animal models. LEA29Y
(BMS-224818), a mutant CTLA4-Ig molecule with increased binding activity, was
evaluated for its potential to replace tacrolimus and protect allogeneic islets
in a preclinical primate model. Animals received either the base
immunosuppression regimen (rapamycin and anti-IL-2R monoclonal antibody [mAb])
or the base immunosuppression and LEA29Y. Animals receiving the LEA29Y/rapamycin/anti-IL-2R
regimen (n = 5) had significantly prolonged islet allograft survival (204, 190,
216, 56, and >220 days). In contrast, those animals receiving the base
regimen alone (n = 2) quickly rejected the transplanted islets at 1 week (both
at 7 days). The LEA29Y-based regimen prevented the priming of anti-donor T- and
B-cell responses, as detected by interferon-gamma enzyme-linked immunospot and
allo-antibody production, respectively. The results of this study suggest that
LEA29Y is a potent immunosuppressant that can effectively prevent rejection in
a steroid-free immunosuppressive protocol and produce marked prolongation of
islet allograft survival in a preclinical model.
----------------------------------------------------
[42]
TÍTULO / TITLE: - Nutrient signaling
through TOR kinases controls gene expression and cellular differentiation in
fungi.
REVISTA
/ JOURNAL: - Curr Top Microbiol Immunol 2004;279:53-72.
AUTORES
/ AUTHORS: - Rohde JR; Cardenas ME
INSTITUCIÓN
/ INSTITUTION: - Department of Molecular Genetics and
Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
RESUMEN
/ SUMMARY: - The TOR kinases were first identified in
Saccharomyces cerevisiae as the targets of the immunosuppressive drug
rapamycin. Subsequent studies employing rapamycin as a tool in yeast have given
us insight into the structure and function of the TOR kinases, as well as the
biological role of the TOR signaling program in transmitting nutrient signals
to promote cell growth. One of the major advances from this area has been in
defining an unexpected role for TOR signaling in the regulation of
transcription. The identification of target genes subject to regulation by TOR
has provided a platform for the dissection of the signaling events downstream
of the TOR kinases. Studies aimed at understanding TOR-regulated transcription
have begun to shed light on how TOR signaling cooperates with other signaling
programs. In addition, the TOR pathway regulates the developmental program of
pseudohyphal differentiation in concert with highly conserved MAP kinase and
PKA signaling programs. Remarkably, rapamycin also blocks filamentation in a
number of important human and plant pathogens and the mechanism of rapamycin
action is conserved in Candida albicans and Cryptococcus neoformans. The
antimicrobial properties of less immunosuppressive analogs of rapamycin hold
promise for the development of an effective antifungal therapy. N. Ref:: 65
----------------------------------------------------
[43]
TÍTULO / TITLE: - Signaling pathways
involved in translational control of protein synthesis in skeletal muscle by
leucine.
REVISTA
/ JOURNAL: - J Nutr. Acceso gratuito al texto completo
a partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.nutrition.org/
●●
Cita: Journal of Nutrition: <> 2001 Mar;131(3):856S-860S.
AUTORES
/ AUTHORS: - Anthony JC; Anthony TG; Kimball SR;
Jefferson LS
INSTITUCIÓN
/ INSTITUTION: - Department of Cellular and Molecular
Physiology, P.O. Box 850, The Pennsylvania State University College of
Medicine, Hershey, PA 17033, USA.
RESUMEN
/ SUMMARY: - Numerous reports established that in
skeletal muscle the indispensable branched-chain amino acid leucine is unique
in its ability to initiate signal transduction pathways that modulate
translation initiation. Oral administration of leucine stimulates protein
synthesis in association with hyperphosphorylation of the translational
repressor, eukaryotic initiation factor (eIF) 4E binding protein 1 (4E-BP1),
resulting in enhanced availability of the mRNA cap-binding protein eIF4E, for
binding eIF4G and forming the active eIF4F complex. In addition, leucine
enhances phosphorylation of the 70-kDa ribosomal protein S6 kinase (S6K1).
These results suggest that leucine upregulates protein synthesis in skeletal
muscle by enhancing both the activity and synthesis of proteins involved in
mRNA translation. The stimulatory effects of leucine on translation initiation
are mediated in part through the protein kinase mammalian target of rapamycin
(mTOR), where both insulin signaling and leucine signaling converge to promote
a maximal response. N.
Ref:: 34
----------------------------------------------------
[44]
TÍTULO / TITLE: - A benefit-risk
assessment of basiliximab in renal transplantation.
REVISTA
/ JOURNAL: - Drug Saf. Acceso gratuito al texto
completo.
●●
Enlace a la Editora de la Revista http://www.csmwm.org/
●●
Cita: Drug Safety: <> 2004;27(2):91-106.
AUTORES
/ AUTHORS: - Boggi U; Danesi R; Vistoli F; Del Chiaro
M; Signori S; Marchetti P; Del Tacca M; Mosca F
INSTITUCIÓN
/ INSTITUTION: - Division of General Surgery and
Transplants, Department of Oncology, Transplants and Advanced Technologies in
Medicine, University of Pisa, Pisa, Italy. uboggi@med.unipi.it
RESUMEN
/ SUMMARY: - Interleukin-2 (IL-2) and its receptor
(IL-2R) play a central role in T lymphocyte activation and immune response
after transplantation. Research on the biology of IL-2R allowed the
identification of key signal transduction pathways involved in the generation
of proliferative and antiapoptotic signals in T cells. The alpha-chain of the
IL-2R is a specific peptide against which monoclonal antibodies have been
raised, with the aim of blunting the immune response by means of inhibiting
proliferation and inducing apoptosis in primed lymphocytes. Indeed,
basiliximab, one of such antibodies, has proved to be effective in reducing the
episodes of acute rejection after kidney and pancreas transplantation. The use
of basiliximab was associated with a significant reduction in the incidence of
any treated rejection episodes after kidney transplantation in the two major
randomised studies (placebo 52.2% vs basiliximab 34.2% at 6 months, European
study; placebo 54.9% vs basiliximab 37.6% at 1 year, US trial). Basiliximab and
equine antithymocyte globulin (ATG) administration resulted in a similar rate
of biopsy-proven acute rejection at 6 months (19% for both) and at 12 months
(19% and 20%, respectively). The use of basiliximab appears not to be
associated with an increased incidence of adverse events as compared with
placebo in immunosuppressive regimens, including calcineurin inhibitors,
mycophenolate mofetil or azathioprine and corticosteroids, and its safety
profile is superior to ATG. Moreover, a similar occurrence of infections is
noted in selected studies (65.5% after basiliximab vs 65.7% of controls),
including cytomegalovirus infection (17.3% vs 14.5%), and cytokine-release
syndrome is not observed. Finally, economic analysis demonstrated lower costs of
overall treatment in patients treated with basiliximab. Therefore, the use of
basiliximab entails a very low risk, allows safe reduction of corticosteroid
dosage and reduces the short- and mid-term rejection rates. However, the
improvement in the long-term survival of kidney grafts in patients treated
according to modern immunosuppressive protocols is still to be demonstrated.
These conclusions are based on a systematic review of the scientific
literature, indexed on Medline database, concerning the mechanism of action,
therapeutic activity, safety and pharmacoeconomic evaluation of basiliximab in
renal transplantation. N.
Ref:: 62
----------------------------------------------------
[45]
TÍTULO / TITLE: - Role of leucine in the
regulation of mTOR by amino acids: revelations from structure-activity studies.
REVISTA
/ JOURNAL: - J Nutr. Acceso gratuito al texto completo
a partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.nutrition.org/
●●
Cita: Journal of Nutrition: <> 2001 Mar;131(3):861S-865S.
AUTORES
/ AUTHORS: - Lynch CJ
INSTITUCIÓN
/ INSTITUTION: - Department of Cellular and Molecular
Physiology, The Pennsylvania State University College of Medicine, 500
University Drive, Hershey, PA 17033, USA. clynch@psu.edu
RESUMEN
/ SUMMARY: - In this study an overview is presented of
the mTOR signaling pathway and its regulation by amino acids, particularly
L-leucine. Our laboratory is studying amino acid regulation of mTOR in
adipocytes. Potential roles for mTOR in adipocytes that were previously posited
include hypertrophic growth, leptin secretion, protein synthesis and adipose
tissue morphogenesis. A current area of interest in the field is how amino
acids regulate mTOR and which amino acids are regulatory. Revelations
concerning mechanism and recognition are emerging from different laboratories
that examined the structural requirements for stimulation and inhibition of the
mTOR signaling pathway by leucine and amino acid analogs. In adipocytes and
some other cell types, leucine appears to be the main regulatory amino acid.
However, this is not uniformly the case. In those cells where mTOR is regulated
by several amino acids, there is evidence that the mechanism of mTOR activation
may be different from cells where mainly leucine is regulatory. Furthermore, in
tissues where leucine regulates mTOR, the possible existence of different
tissue-specific leucine recognition sites may be indicated. N. Ref:: 47
----------------------------------------------------
[46]
TÍTULO / TITLE: - Drug-eluting stents and
glycoprotein IIb/IIIa inhibitors: combination therapy for the future.
REVISTA
/ JOURNAL: - Am Heart J 2003 Oct;146(4 Suppl):S13-7.
●●
Enlace al texto completo (gratuito o de pago) 1016/j.ahj.2003.09.004
AUTORES
/ AUTHORS: - Leon MB; Bakhai A
RESUMEN
/ SUMMARY: - BACKGROUND: Although coronary stenting has
improved the results of coronary interventions compared to coronary angioplasty
alone, in-stent restenosis remains a significant limitation of this procedure.
Drug-eluting stents with or without glycoprotein IIb/IIIa inhibitor therapy
represent an additional advance in the evolution of this strategy. METHODS: We
review the currently available trials comparing studies of non-drug-eluting and
drug-eluting stents using sirolimus and paclitaxel agents and their
derivatives. RESULTS: Ten studies are available that compare drug-eluting to
traditional non-drug-eluting stents. A variety of antiplatelet regimes have
been used. The majority of these studies are in the process of being published.
No head-to-head studies comparing different drug-eluting stents are available.
CONCLUSIONS: Drug-eluting stents using sirolimus and paclitaxel in combination
with enhanced antiplatelet strategies represent an important advantage over
non-drug-eluting stents for the reduction of in-stent restenosis. The rate at
which drug-eluting stents are adapted into widespread practice depends heavily
on whether they are safe, efficacious, and cost-effective in various clinical
settings. N. Ref:: 28
----------------------------------------------------
[47]
TÍTULO / TITLE: - Tissue factor and
coronary artery disease.
REVISTA
/ JOURNAL: - Cardiovasc Res 2002 Feb 1;53(2):313-25.
AUTORES
/ AUTHORS: - Moons AH; Levi M; Peters RJ
INSTITUCIÓN
/ INSTITUTION: - Department of Cardiology, Academic Medical
Center, Room F3-236, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
RESUMEN
/ SUMMARY: - Plaque disruption with superimposed
thrombosis is the main cause of acute coronary events such as acute myocardial
infarction and unstable angina. Among other factors, tissue factor seems to
play an important role determining plaque thrombogenicity. Tissue factor is a
potent initiator of the coagulation cascade situated within the vessel wall and
is highly exposed to the blood after plaque rupture. Several mediators involved
in the process of atherosclerotic plaque formation are capable of inducing
tissue factor expression in cells such as monocytes, macrophages and
endothelial cells, which under normal conditions do not express tissue factor
or to a limited extent only. The increased expression of tissue factor is not
limited to the plaque but is also found in circulating monocytes in patients
with acute coronary syndromes. In addition, studies have shown an important
contribution of tissue factor in the pathogenesis of thrombosis and restenosis
after balloon angioplasty. Recent basic studies focus on the therapeutic
inhibition of tissue factor. Specific and non-specific inhibitors of tissue
factor or the tissue factor/factor VIIa complex have been developed or
identified, and have been tested in experimental studies. Clinical studies are
currently being initiated. In this review, we present the current knowledge on
the role of tissue factor in atherosclerosis, arterial intervention and potential
pharmacological approaches, with focus on acute coronary syndromes. N. Ref:: 162
----------------------------------------------------
[48]
- Castellano -
TÍTULO / TITLE:Las inmunofilinas: agentes
neuroprotectores y promotores de la regeneracion neural. Immunophilins:
neuroprotective agents and promoters of neural regeneration.
REVISTA
/ JOURNAL: - Neurologia. Acceso gratuito al texto
completo.
●●
Enlace a la Editora de la Revista http://www.stmeditores.com/Revistas/ffasciculo.php?Mw==&MTk=&MjUy
●●
Cita: Neurologia: <> 2002 Apr;17(4):200-13.
AUTORES
/ AUTHORS: - Udina E; Navarro X
INSTITUCIÓN
/ INSTITUTION: - Grupo de Neuroplasticidad y Regeneracion,
Departamento de Biologia Celular, Fisiologia e Inmunologia, Universitat
Autonoma de Barcelona, Bellaterra, España.
RESUMEN
/ SUMMARY: - Immunophilins are a family of proteins
mainly known because they act as receptors of the immunosuppressant drugs
cyclosporin A (CsA) and FK506. Immunophilins serve several general functions,
including regulation of mitochondrial permeability, modulation of ion channels
stability and acting as chaperones for a variety of proteins. However,
immunophilins are also present at high density in the nervous system. CsA,
FK506 and other derivatives inhibit the function of immunophilins and, through
bloking or activating several intracellular pathways, it has been shown that
they exert neuroprotective effects in different experimental models of
ischemia, Parkinson’s disease and excitotoxic insults. Moreover, FK506 also has
neuroregenerative effects, by enhancing the axonal regeneration rate after
lesions of the peripheral nervous system. The development of new agents that
selectively bind to immunophilins opens new interesting perspectives for the
therapy of degenerative diseases and injuries of the nervous system. N. Ref:: 100
----------------------------------------------------
[49]
TÍTULO / TITLE: - Immunoablation followed
or not by hematopoietic stem cells as an intense therapy for severe autoimmune
diseases. New perspectives, new problems.
REVISTA
/ JOURNAL: - Haematologica. Acceso gratuito al texto
completo.
●●
Enlace a la Editora de la Revista http://db.doyma.es/
●●
Cita: Haematologica: <> 2001 Apr;86(4):337-45.
AUTORES
/ AUTHORS: - Marmont AM N. Ref:: 127
----------------------------------------------------
[50]
TÍTULO / TITLE: - Protein phosphatase 2A
on track for nutrient-induced signalling in yeast.
REVISTA
/ JOURNAL: - Mol Microbiol. Acceso gratuito al texto
completo a partir de los 2 años de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.blackwell-synergy.com/
●●
Cita: Molecular Microbiology: <> 2002 Feb;43(4):835-42.
AUTORES
/ AUTHORS: - Zabrocki P; Van Hoof C; Goris J; Thevelein
JM; Winderickx J; Wera S
INSTITUCIÓN
/ INSTITUTION: - Laboratorium voor Moleculaire Celbiologie,
K.U.Leuven, Kasteelpark Arenberg 31, B-3001 Leuven-Heverlee, Flanders, Belgium.
RESUMEN
/ SUMMARY: - Early studies identified two bona fide
protein phosphatase 2A (PP2A)-encoding genes in Saccharomyces cerevisiae,
designated PPH21 and PPH22. In addition, three PP2A-related phosphatases,
encoded by PPH3, SIT4 and PPG1, have been identified. All share as much as 86%
sequence similarity at the amino acid level. This review will focus primarily
on Pph21 and Pph22, but some aspects of Sit4 regulation will also be discussed.
Whereas a role for PP2A in yeast morphology and cell cycle has been readily
recognized, uncovering its function in yeast signal transduction is a more
recent breakthrough. Via their interaction with phosphorylated Tap42, PP2A and
Sit4 play a pivotal role in target of rapamycin (TOR) signalling. PPH22
overexpression mimics overactive cAMP-PKA (protein kinase A) signalling and
PP2A and Sit4 might represent ceramide signalling targets. The methylation of
its catalytic subunit stabilizes the heterotrimeric form of PP2A and might
counteract TOR signalling. We will show how these new elements could lead us to
understand the role and regulation of PP2A in nutrient-induced signalling in
baker’s yeast. N.
Ref:: 41
----------------------------------------------------
[51]
TÍTULO / TITLE: - mTOR as a target for
cancer therapy.
REVISTA
/ JOURNAL: - Curr Top Microbiol Immunol
2004;279:339-59.
AUTORES
/ AUTHORS: - Houghton PJ; Huang S
INSTITUCIÓN
/ INSTITUTION: - Department of Molecular Pharmacology, St.
Jude Children’s Research Hospital, 332 N. Lauderdale, Memphis, TN 38105-2794,
USA. peter.houghton@stjude.org
RESUMEN
/ SUMMARY: - The target of rapamycin, mTOR, acts as a
sensor for mitogenic stimuli, such as insulin-like growth factors and cellular
nutritional status, regulating cellular growth and division. As many tumors are
driven by autocrine or paracrine growth through the type-I insulin-like growth
factor receptor, mTOR is potentially an attractive target for
molecular-targeted treatment. Further, a rationale for anticipating
tumor-selective activity based on transforming events frequently identified in
malignant disease is becoming established.
N. Ref:: 73
----------------------------------------------------
[52]
TÍTULO / TITLE: - Serine-threonine
protein phosphatase inhibitors: development of potential therapeutic
strategies.
REVISTA
/ JOURNAL: - J Med Chem 2002 Mar 14;45(6):1151-75.
AUTORES
/ AUTHORS: - McCluskey A; Sim AT; Sakoff JA
INSTITUCIÓN
/ INSTITUTION: - School of Biological & Chemical
Science, Medicinal Chemistry Group, The University of Newcastle, Callaghan, NSW
2308, Australia. amcclusk@mail.newcastle.edu.au N. Ref:: 329
----------------------------------------------------
[53]
TÍTULO / TITLE: - Inflammatory
myopathies: clinical, diagnostic and therapeutic aspects.
REVISTA
/ JOURNAL: - Muscle Nerve 2003 Apr;27(4):407-25.
●●
Enlace al texto completo (gratuito o de pago) 1002/mus.10313
AUTORES
/ AUTHORS: - Mastaglia FL; Garlepp MJ; Phillips BA;
Zilko PJ
INSTITUCIÓN
/ INSTITUTION: - Centre for Neuromuscular and Neurological
Disorders, University of Western Australia, Queen Elizabeth II Medical Centre,
Nedlands, Australia. flmast@cyllene.uwa.edu.au
RESUMEN
/ SUMMARY: - The three major forms of immune-mediated
inflammatory myopathy are dermatomyositis (DM), polymyositis (PM), and
inclusion-body myositis (IBM). They each have distinctive clinical and
histopathologic features that allow the clinician to reach a specific diagnosis
in most cases. Magnetic resonance imaging is sometimes helpful, particularly if
the diagnosis of IBM is suspected but has not been formally evaluated.
Myositis-specific antibodies are not helpful diagnostically but may be of
prognostic value; most antibodies have low sensitivity. Muscle biopsy is
mandatory to confirm the diagnosis of an inflammatory myopathy and to allow
unusual varieties such as eosinophilic, granulomatous, and parasitic myositis,
and macrophagic myofasciitis, to be recognized. The treatment of the
inflammatory myopathies remains largely empirical and relies upon the use of
corticosteroids, immunosuppressive agents, and intravenous immunoglobulin, all
of which have nonselective effects on the immune system. Further controlled
clinical trials are required to evaluate the relative efficacy of the available
therapeutic modalities particularly in combinations, and of newer
immunosuppressive agents (mycophenolate mofetil and tacrolimus) and
cytokine-based therapies for the treatment of resistant cases of DM, PM, and
IBM. Improved understanding of the molecular mechanisms of muscle injury in the
inflammatory myopathies should lead to the development of more specific forms
of immunotherapy for these conditions. N.
Ref:: 256
----------------------------------------------------
[54]
TÍTULO / TITLE: - Mitochondrial
permeability transition in acute neurodegeneration.
REVISTA
/ JOURNAL: - Biochimie 2002 Feb-Mar;84(2-3):241-50.
AUTORES
/ AUTHORS: - Friberg H; Wieloch T
INSTITUCIÓN
/ INSTITUTION: - Laboratory for Experimental Brain
Research, Wallenberg Neuroscience Center, BMC A13, 221 84 Lund, Sweden.
RESUMEN
/ SUMMARY: - Acute neurodegeneration in man is
encountered during and following stroke, transient cardiac arrest, brain
trauma, insulin-induced hypoglycemia and status epilepticus. All these severe
clinical conditions are characterized by neuronal calcium overload, aberrant
cell signaling, generation of free radicals and elevation of cellular free
fatty acids, conditions that favor activation of the mitochondrial permeability
transition pore (mtPTP). Cyclosporin A (CsA) and its analog
N-methyl-valine-4-cyclosporin A (MeValCsA) are potent blockers of the mtPTP and
protect against neuronal death following excitotoxicity and oxygen glucose
deprivation. Also, CsA and MeValCsA diminish cell death following cerebral
ischemia, trauma, and hypoglycemia. Here we present data that strongly imply
the mtPT in acute neurodegeneration in vivo. Compounds that readily pass the
blood-brain-barrier (BBB) and block the mtPT may be neuroprotective in
stroke. N. Ref:: 100
----------------------------------------------------
[55]
TÍTULO / TITLE: - Calcineurin-free
protocols with basiliximab induction allow patients included in “old to old”
programs achieve standard kidney transplant function.
REVISTA
/ JOURNAL: - Transplant Proc 2003 Jun;35(4):1326-7.
AUTORES
/ AUTHORS: - Emparan C; Laukotter M; Wolters H; Dame C;
Heidenreich S; Senninger N
INSTITUCIÓN
/ INSTITUTION: - Department of Surgery, Division of
Transplantation, Uniklinikum Munster, Munster, Germany. cemparan@teleline.es
RESUMEN
/ SUMMARY: - INTRODUCTION: The EuroTransplant “old to
old” program establishes that patients older than 60 years can receive offers
of organs from donors older than 60 years. The compromised function of these
organs makes it a priority to preserve their initial kidney function.
HYPOTHESIS: Calcineurin-sparing protocols using anti-IL-2 receptor (IL-2R)
antibody induction (Simulect) may benefit initial kidney function in these
patients, as assessed by the rates of delayed graft function and of rejection
during the first month after transplant. PATIENTS AND METHODS: A cohort of 15
consecutive elderly patients were prospectively compared with 30 cadaveric
kidney transplants in younger recipients. Study patients were induced with
Simulect (20 mg, 30 minutes before reperfusion and 4 days after
transplantation) and steroids, delaying the introduction of CsA until the serum
creatinine was below 3 mg/dL. The other cohort of patients were
immunosuppressed with tacrolimus (trough 8 to 12), mycophenolats mofetil (MMF,
1 g/d), and an identical taper of steroids. The analysis compared donor and
recipient ages, mean cold ischemic time, incidence of initial kidney function
(diuresis in the first 24 h) serum creatinine levels, glomerular filtration
rate (GFR), number of dialysis sessions, and rejection rate in the two groups.
RESULTS: Except for the donor and recipient ages (72 vs 54 in donors, and 67
versus 52 years in recipients), no significant differences were observed
between the groups among the rates of acute rejection (6.6% vs 13.2%), delayed
graft function (13.2% required dialysis), or infection (6.6%). Within 1 month
all 45 grafts showed primary function with equal creatinine levels (mean 1.65).
CONCLUSIONS: Calcineurin-free protocols using IL-2 therapy as the initial
suppression allow patients in the “old to old” ET program to display equal
results to cadaveric kidney transplants with initial treatment with calcineurin
antagonists.
----------------------------------------------------
[56]
TÍTULO / TITLE: - Measle virus-infected
dendritic cells develop immunosuppressive and cytotoxic activities.
REVISTA
/ JOURNAL: - Immunobiology 2001 Dec;204(5):629-38.
AUTORES
/ AUTHORS: - Vidalain PO; Azocar O; Rabourdin-Combe C;
Servet-Delprat C
INSTITUCIÓN
/ INSTITUTION: - Immunobiologie Fondamentale et Clinique,
CERVI-INSERM, Lyon, France. servet@cervi-lyon.inserm.fr
RESUMEN
/ SUMMARY: - Measle virus (MV) infection induces a
transient but profound immunosuppression characterized by a panlymphopenia
which occasionally results in opportunistic infections responsible for a high
rate of mortality in malnourished children. MV can encounter human dendritic
cells (DC) in the respiratory mucosa or in the secondary lymphoid organs. After
a brief presentation of DCs, we review progress in understanding the
immunobiology of MV-infected DCs that could account for MV-induced
immunosuppression. In addition, we develop the newly described TRAIL-mediated
cytotoxic function of DCs that is turned on by MV infection, but also by
interferons or double-stranded RNA (poly (I:C)). Finally, we propose a model
where the measles-associated lymphopenia could be mediated by TRAIL and the
measles-induced immunosuppression could be transiently prolonged by
Fas-mediated destruction of DCs. N.
Ref:: 38
----------------------------------------------------
[57]
TÍTULO / TITLE: - Antiproliferative
prostaglandins and the MRP/GS-X pump role in cancer immunosuppression and
insight into new strategies in cancer gene therapy.
REVISTA
/ JOURNAL: - Biochem Pharmacol 2001 Oct 1;62(7):811-9.
AUTORES
/ AUTHORS: - Homem de Bittencourt PI Jr; Curi R
INSTITUCIÓN
/ INSTITUTION: - Department of Physiology, Institute of
Basic Health Sciences, Federal University of Rio Grande do Sul, Rua Sarmento
Leite 500, 90050-170, Porto Alegre, RS, Brazil. pauloivo@vortex.ufrgs.br
RESUMEN
/ SUMMARY: - A dramatic complication in late-stage
cancer patients is host immunosuppression. Cyclopentenone prostaglandins
(CP-PGs) overproduced in cancer may impair the function of the immune system.
These agents, if produced at high concentrations, are powerful cytostatic and
cytotoxic compounds that may arrest cell proliferation and immune response in
cancer. Lymphoid tissues of tumor-bearing animals accumulate large amounts of
CP-PGs, whereas the tumor tissue does not. This may be because cancer cells are
able to overexpress multidrug resistance-associated protein (Mg(2+)-dependent
vanadate-sensitive GS-conjugate export ATPase, MRP/GS-X pump), which extrudes
CP-PGs to the extracellular space as glutathione S-conjugates. In contrast,
MRP/GS-X pump activity is disproportionately low in lymphocytes. This led us to
propose the transfection of lymphocytes with multidrug resistance-associated
protein genes (MRP) for further autologous transfusion or direct in vivo
delivery to lymphocytes by using adenovirus-retrovirus chimeras in order to
restore immune system function in cancer, at least partially. We are currently
evaluating MRP-transfected lymphocyte (MTL) therapy, using Walker 256
tumor-bearing rats as a model. N.
Ref:: 49
----------------------------------------------------
[58]
TÍTULO / TITLE: - Cytokine and
anti-cytokine therapies for inflammatory bowel disease.
REVISTA
/ JOURNAL: - Curr Pharm Des 2003;9(14):1107-13.
AUTORES
/ AUTHORS: - Ogata H; Hibi T
INSTITUCIÓN
/ INSTITUTION: - Department of Internal Medicine, Keio
University School of Medicine, Tokyo, Japan.
RESUMEN
/ SUMMARY: - Although the pathogenesis of inflammatory
bowel disease (IBD) remains elusive, it appears that there is chronic
activation of the immune and inflammatory cascade in genetically susceptible
individuals. Current disease management guidelines have therefore focused on
the use of anti-inflammatory agents, aminosalicylates and corticosteroids.
These conventional therapies continue to be a first choice in the management of
IBD. Immunomodulators, such as azathioprine, 6-mercaptopurine, methotrexate or
cyclosporin, are demonstrating increasing importance against steroid-resistant
and steroid-dependent patients. However, some patients are still refractory to
these therapies. Recent advances in the understanding of the pathophysiological
conditions of IBD have provided new immune system modulators as therapeutic
tools. Other immunosuppressive agents including FK506 and thalidomide have
expanded the choice of medical therapies available for certain subgroups of
patients. Furthermore, biological therapies have begun to assume a prominent
role. Studies with chimeric monoclonal anti-TNF-alpha antibody treatment have
been reported with dramatic successes. However, observations in larger numbers
of treated patients are needed to explicate fully the safety of or risks posed
by this agent such as developing lymphoma, or other malignancies. Another
anti-inflammatory cytokine-therapy includes anti anti-IL-6R, anti-IL-12 or
toxin-conjugated anti IL-7R, recombinant cytokines (IL-10 or IL-11). Given the
diversity of proinflammatory products under its control, NF-kappaB may be
viewed as a master switch in lymphocytes and macrophages, regulating
inflammation and immunity. Although some of them still need more confirmatory
studies, those immune therapies will provide new insights into cell-based and
gene-based treatment against IBD in near future. N. Ref:: 46
----------------------------------------------------
[59]
TÍTULO / TITLE: - Amino acid transport
regulates blastocyst implantation.
REVISTA
/ JOURNAL: - Biol Reprod. Acceso gratuito al texto
completo a partir de los 2 años de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.biolreprod.org/
●●
Cita: Biol Reprod: <> 2003 Oct;69(4):1101-8. Epub 2003 Jun 11.
●●
Enlace al texto completo (gratuito o de pago) 1095/biolreprod.103.018010
AUTORES
/ AUTHORS: - Martin PM; Sutherland AE; Van Winkle LJ
INSTITUCIÓN
/ INSTITUTION: - Department of Cell Biology, University of
Virginia, Charlottesville, Virginia, USA.
RESUMEN
/ SUMMARY: - Mouse blastocyst outgrowth in vitro and
probably implantation in vivo require amino acid signaling via the target of
rapamycin (TOR) pathway. This signaling does not simply support protein
synthesis and trophoblast differentiation. Rather, it regulates development of
trophoblast protrusive activity and may act as a developmental checkpoint for
implantation. Moreover, intracellular amino acids per se are insufficient to
elicit TOR signaling. Instead, de novo transport of amino acids, and
particularly of leucine, stimulate mTOR activity at the blastocyst stage. The
activity of the broad-scope and yet leucine-selective amino acid transport
system B0,+ could produce such increases in intracellular amino acid
concentrations. For example, system B0,+ uses a Na+ gradient to drive amino
acid uptake, and the Na+ concentration in uterine secretions increases by nearly
two-fold about 18 h before implantation. The resultant mTOR signaling could
trigger polyamine, insulin-like growth factor II, and nitric oxide production
in blastocysts and the increased cell motility sometimes associated with
synthesis of these bioactive molecules.
N. Ref:: 106
----------------------------------------------------
[60]
TÍTULO / TITLE: - Introduction and
overview: recent advances in the immunotherapy of inflammatory bowel disease.
REVISTA
/ JOURNAL: - J Gastroenterol 2003 Mar;38 Suppl 15:36-42.
AUTORES
/ AUTHORS: - Hibi T; Inoue N; Ogata H; Naganuma M
INSTITUCIÓN
/ INSTITUTION: - Department of Internal Medicine, Keio
University School of Medicine, Center for the Research of Inflammatory Bowel
Disease, Keio University School of Medicine, Tokyo, Japan.
RESUMEN
/ SUMMARY: - Ulcerative colitis (UC) and Crohn’s
disease (CD) comprise a series of inflammatory bowel disease (IBD) resulting
from chronic upregulation of the mucosal immune system. Although the
pathogenesis of IBD remains elusive, it appears that there is chronic
activation of the immune and inflammatory cascade in genetically susceptible
individuals. Current disease management guidelines have therefore focused on
the use of antiinflammatory agents, aminosalicylates and corticosteroids.
However, some patients are still refractory to these therapies. Recent advances
in the understanding of the pathophysiological conditions of IBD have provided
new immune system modulators as therapeutic tools. Cytapheresis has
demonstrated effectiveness against UC and has practical use in Japan.
Immunosuppressive agents including cyclosporin A and tacrolimus (FK506) have
expanded the choice of medical therapies available for certain subgroups of
patients. Furthermore, biological therapies have begun to assume a prominent
role. Studies with chimeric monoclonal anti-TNF-alpha antibody treatment of CD
have been reported with dramatic success. Another antiinflammatory cytokine
therapy includes anti-IL-6 receptor, anti-IL-12, or toxin-conjugated anti-IL-7 receptor.
Given the diversity of proinflammatory products under its control, NF-kappa B
may be viewed as a master switch in lymphocytes and macrophages, regulating
inflammation and immunity. In the murine 2,4,6-trinitrobenzen sulfonic acid
(TNBS) colitis model, an antisense oligonucleotide to NF-kappa B p65
ameliorated inflammation even after induction of colitis. Recently, a clinical
pilot trial of this agent demonstrated promising results. Accumulating evidence
suggests that luminal bacterial flora is a requisite and central factor in the
development of IBD. Probiotic therapies such as a nonpathogenic Escherichia
coli strain have been well tolerated, but larger clinical trials are needed. In
addition, novel therapeutic strategies targeting adhesion molecules and
costimulatory molecules, or enhancing tissue repair, are under investigation.
Although some still need more confirmatory studies, these immune therapies will
provide new insights into cell-based and gene-based treatment against IBD in
the near future. N.
Ref:: 36
----------------------------------------------------
[61]
TÍTULO / TITLE: - Potassium channels in T
lymphocytes: toxins to therapeutic immunosuppressants.
REVISTA
/ JOURNAL: - Toxicon 2001 Sep;39(9):1269-76.
AUTORES
/ AUTHORS: - George Chandy K; Cahalan M; Pennington M;
Norton RS; Wulff H; Gutman GA
INSTITUCIÓN
/ INSTITUTION: - Department of Physiology and Biophysics,
University of California Irvine, Room 291, John Irvine Smith Hall, Medical
School, Irvine, CA92697, USA. gchandy@uci.edu N. Ref:: 60
----------------------------------------------------
[62]
TÍTULO / TITLE: - Graft vascular function
after transplantation of pancreatic islets.
REVISTA
/ JOURNAL: - Diabetologia 2002 Jun;45(6):749-63. Epub
2002 May 15.
●●
Enlace al texto completo (gratuito o de pago) 1007/s00125-002-0827-4
AUTORES
/ AUTHORS: - Jansson L; Carlsson PO
INSTITUCIÓN
/ INSTITUTION: - Department of Medical Cell Biology,
Biomedical Center, Uppsala University, Box 571, 751 23 Uppsala, Sweden. Leif.Jansson@medcellbiol.uu.se
RESUMEN
/ SUMMARY: - Endogenous pancreatic islets have a dense
glomerular-like angioarchitecture, which ensures an optimal delivery of oxygen
and nutrients to the islet cells, provides signals from other cells in the body
and disposes secreted hormones. Transplantation of isolated islets means that
their vascular connection is interrupted. The islet grafts therefore depend
upon endothelial cells and microvessels originating in the implantation organ
for derivation of a new vascular system. A re-establishment of islet blood-flow
occurs within 7-14 days after transplantation, mainly through vascular
sprouting. The newly formed blood vessels acquire the morphological
characteristics of those in endogenous islets. In intraportally transplanted
islets to the liver, the islets become revascularized almost exclusively from
tributaries to the hepatic artery. Exocrine contamination of the transplanted
islets could hamper the revascularization process, whereas neither
cryopreservation nor immunosuppressive drugs like cyclosporin, prednisolon and
RS-61443 have any essential effects on the angiogenesis. Investigators have noticed
improvements in islet graft survival and function by means of basic fibroblast
growth factor (bFGF), acidic FGF and endothelial cell growth factor exposure of
the grafts. The functional properties of transplanted islets are largely
unknown, but evidence from experimental islet transplantation suggests that
both the blood perfusion and the tissue oxygen tension of the grafted islets
are chronically decreased, indicating an insufficient vascular system. In order
to achieve optimal condition for survival and function of transplanted beta
cells, it is important to ascertain whether impairments in vascular function
are present also after clinical islet transplantations as well. N. Ref:: 181
----------------------------------------------------
[63]
TÍTULO / TITLE: - Targeted cancer therapy
and immunosuppression using radiolabeled monoclonal antibodies.
REVISTA
/ JOURNAL: - Semin Oncol 2004 Feb;31(1):68-82.
AUTORES
/ AUTHORS: - Bethge WA; Sandmaier BM
INSTITUCIÓN
/ INSTITUTION: - Clinical Research Division, Fred
Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
RESUMEN
/ SUMMARY: - Radioimmunotherapy (RIT) as a means to
target radiation therapy to tumor cells or to specifically suppress host
immunity specifically in the setting of allogeneic transplantation is a
promising new strategy in the armory of today’s oncologist. Different
approaches of RIT such as injection of a stable radioimmunoconjugate or the use
of pretargeting are available. The choice of the radionuclide used for RIT
depends on its radiation characteristics with respect to the malignancy or
cells targeted. beta-Emitters with their lower energy and longer path length
are more suitable for targeting bulky, solid tumors, whereas alpha-emitters
with their high linear energy transfer and short path length are better suited
to target cells or tumors of the hematologic system. Encouraging results have
been obtained using these approaches treating patients with hematologic
malignancies. While the results in solid tumors are somewhat less favorable,
new strategies for patients with minimal residual disease (MRD), using adjuvant
and locoregional treatment, are currently being investigated. In this report,
we outline basic principles of RIT, give an overview of available
radioimmunoconjugates and their clinical applications with special emphasis on
their use in hematologic malignancies, including use in conditioning regimens
for stem cell transplantation (SCT). N.
Ref:: 99
----------------------------------------------------
[64]
TÍTULO / TITLE: - TOR inhibitors and
cardiac allograft vasculopathy: is inhibition of intimal thickening an adequate
surrogate of benefit?
REVISTA
/ JOURNAL: - J Heart Lung Transplant 2003
May;22(5):501-4.
AUTORES
/ AUTHORS: - Mehra MR; Uber PA
INSTITUCIÓN
/ INSTITUTION: - Cardiomyopathy and Heart Transplantation
Center, Ochsner Clinic Foundation, New Orleans, Louisiana 70121, USA. mmehra@ochsner.org N. Ref:: 30
----------------------------------------------------
[65]
TÍTULO / TITLE: - The TOR kinases link
nutrient sensing to cell growth.
REVISTA
/ JOURNAL: - J Biol Chem. Acceso gratuito al texto
completo a partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.jbc.org/
●●
Cita: J. of Biological Chemistry: <> 2001 Mar 30;276(13):9583-6. Epub
2001 Feb 2.
●●
Enlace al texto completo (gratuito o de pago) 1074/jbc.R000034200
AUTORES
/ AUTHORS: - Rohde J; Heitman J; Cardenas ME
INSTITUCIÓN
/ INSTITUTION: - Departments of Genetics, Howard Hughes
Medical Institute, Duke University Medical Center, Durham, North Carolina 27710,
USA.
RESUMEN
/ SUMMARY: - Rapamycin is an immunosuppressive natural
product that inhibits the proliferation of T-cells in response to nutrients and
growth factors. Rapamycin binds to the peptidyl-prolyl isomerase FKBP12 and
forms protein-drug complexes that inhibit signal transduction by the TOR
kinases. The FKBP12 and TOR proteins are conserved from fungi to humans, and in
both organisms the TOR signaling pathway plays a role in nutrient sensing. In
response to nitrogen sources or amino acids, TOR regulates both transcription
and translation, enabling cells to appropriately respond to growth-promoting
signals. Rapamycin is having a profound impact on clinical medicine and was
approved as an immunosuppressant for transplant recipients in 1999. Ongoing clinical
studies address new clinical applications for rapamycin as an antiproliferative
drug for chemotherapy and invasive cardiology.
N. Ref:: 74
----------------------------------------------------
[66]
TÍTULO / TITLE: - Hepatitis C virus
infection and vasculitis: implications of antiviral and immunosuppressive
therapies.
REVISTA
/ JOURNAL: - Arthritis Rheum 2002 Mar;46(3):585-97.
●●
Enlace al texto completo (gratuito o de pago) 1002/art.10107 [pii
●●
Enlace al texto completo (gratuito o de pago) 1002/art.10107
AUTORES
/ AUTHORS: - Vassilopoulos D; Calabrese LH
INSTITUCIÓN
/ INSTITUTION: - Hippokration General Hospital, Athens
University, Athens, Greece. N.
Ref:: 92
----------------------------------------------------
[67]
TÍTULO / TITLE: - Transmitting the signal
of excess nitrogen in Saccharomyces cerevisiae from the Tor proteins to the
GATA factors: connecting the dots.
REVISTA
/ JOURNAL: - FEMS Microbiol Rev 2002 Aug;26(3):223-38.
AUTORES
/ AUTHORS: - Cooper TG
INSTITUCIÓN
/ INSTITUTION: - Department of Molecular Sciences,
University of Tennessee, 858 Madison Ave., Memphis, TN 38163, USA. tcooper@utmem.edu
RESUMEN
/ SUMMARY: - Major advances have recently occurred in
our understanding of GATA factor-mediated, nitrogen catabolite repression
(NCR)-sensitive gene expression in Saccharomyces cerevisiae. Under
nitrogen-rich conditions, the GATA family transcriptional activators, Gln3 and
Gat1, form complexes with Ure2, and are localized to the cytoplasm, which
decreases NCR-sensitive expression. Under nitrogen-limiting conditions, Gln3
and Gat1 are dephosphorylated, move from the cytoplasm to the nucleus, in
wild-type but not rna1 and srp1 mutants, and increase expression of
NCR-sensitive genes. ‘Induction’ of NCR-sensitive gene expression and
dephosphorylation of Gln3 (and Ure2 in some laboratories) when cells are
treated with rapamycin implicates the Tor1/2 signal transduction pathway in
this regulation. Mks1 is posited to be a negative regulator of Ure2, positive
regulator of retrograde gene expression and to be itself negatively regulated
by Tap42. In addition to Tap42, phosphatases Sit4 and Pph3 are also argued by
some to participate in the regulatory pathway. Although a treasure trove of
information has recently become available, much remains unknown (and sometimes
controversial) with respect to the precise biochemical functions and regulatory
pathway connections of Tap42, Sit4, Pph3, Mks1 and Ure2, and how precisely Gln3
and Gat1 are prevented from entering the nucleus. The purpose of this review is
to provide background information needed by students and investigators outside
of the field to follow and evaluate the rapidly evolving literature in this
exciting field. N.
Ref:: 61
----------------------------------------------------
[68]
TÍTULO / TITLE: - Interactions between
cyclosporin and lipid-lowering drugs: implications for organ transplant
recipients.
REVISTA
/ JOURNAL: - Drugs 2003;63(4):367-78.
AUTORES
/ AUTHORS: - Asberg A
INSTITUCIÓN
/ INSTITUTION: - Laboratory for Renal Physiology, Section
of Nephrology, Medical Department, The National Hospital, Oslo, Norway. anderas@klinmed.uio.no
RESUMEN
/ SUMMARY: - Dyslipidaemia is more frequent in solid
organ transplant recipients than in the general population, primarily as a
result of immunosuppressive drug treatment. Both cyclosporin and
corticosteroids are associated with dyslipidaemic adverse effects. In order to
reduce the overall cardiovascular risk in these patients, lipid-lowering drugs
have become widely used, especially HMG-CoA reductase inhibitors (statins).
Cyclosporin, as well as most statins (lovastatin, simvastatin, atorvastatin and
pravastatin) are metabolised by cytochrome P450 (CYP)3A4, so a bilateral
pharmacokinetic interaction between these drugs is theoretically possible.
However, results from several studies show that statins do not induce increased
systemic exposure of cyclosporin. A small (but not clinically relevant)
reduction in systemic exposure of cyclosporin has actually been shown in many
studies. Cyclosporin-treated patients on the other hand show several-fold
higher systemic exposure of all statins, both those that are metabolised by
CYP3A4 and fluvastatin (metabolised by CYP2C9). Therefore, the mechanism for
this interaction does not seem to be solely caused by inhibition of CYP3A4
metabolism, but it is probably also a result of inhibition of statin-transport
in the liver, at least in part. Other lipid-lowering drugs, such as fibric acid
derivatives, bile acid sequestrants, probucol, fish oils and orlistat are also
used in solid organ transplant recipients. Most of them do not interact with
cyclosporin, but there are reports indicating that both probucol and orlistat
may reduce cyclosporin bioavailablility to a clinically relevant degree. There
is no information on possible interaction effects of cyclosporin on the
pharmacokinetics of lipid-lowering drugs other than statins, but it is not
likely that any clinical relevant interference exists with fish oil, orlistat,
probucol or bile acid sequestrants. N.
Ref:: 71
----------------------------------------------------
[69]
TÍTULO / TITLE: - European best practice
guidelines for renal transplantation. Section IV: Long-term management of the
transplant recipient. IV.3.1 Long-term immunosuppression. Late steroid or
cyclosporine withdrawal.
REVISTA
/ JOURNAL: - Nephrol Dial Transplant. Acceso gratuito
al texto completo a partir de los 2 años de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://ndt.oupjournals.org/
●●
Cita: Nephrology Dialysis Transplantation: <> 2002;17 Suppl 4:19-20.
RESUMEN
/ SUMMARY: - GUIDELINES: A. In order to reduce or avoid
long-term serious adverse effects of corticosteroids, such as bone fractures,
diabetes mellitus, arterial hypertension, osteoporosis and eye complications,
steroid withdrawal should be considered. B. Steroid withdrawal is safe only in
a proportion of graft recipients and is recommended only in low-risk patients.
The efficacy of the remaining immunosuppression should be considered. C. After
steroid withdrawal, graft function has to be monitored very carefully because
of the risk of a delayed but continuous loss of function due to chronic graft
dysfunction. In the case of functional deterioration or dysfunction, steroids
should be re-administered. D. Cyclosporine withdrawal might be considered in
order to ameliorate nephrotoxicity, arterial hypertension, lipid disorders and
hypertrichosis. This can be carried out with no significant long-term risk of
progressive graft loss. The efficacy of the remaining immunosuppression should
be considered. After cyclosporine withdrawal, careful monitoring for acute
rejection is recommended.
----------------------------------------------------
[70]
TÍTULO / TITLE: - Fluorescence
polarization detection for affinity capillary electrophoresis.
REVISTA
/ JOURNAL: - Electrophoresis 2002 Mar;23(6):903-8.
●●
Enlace al texto completo (gratuito o de pago) 1002/1522-2683(200203)23:6<903::AID-ELPS903>3.0.CO;2-2
[pii]
AUTORES
/ AUTHORS: - Le XC; Wan QH; Lam MT
INSTITUCIÓN
/ INSTITUTION: - Environmental Health Sciences Program,
Department of Public Health Sciences, Faculty of Medicine, University of
Alberta, Edmonton, Alberta T6G 2G3, Canada. xc.le@ualberta.ca
RESUMEN
/ SUMMARY: - Affinity capillary electrophoresis (ACE)
with laser-induced fluorescence polarization (LIFP) detection is described,
with examples of affinity interaction studies. Because fluorescence
polarization is sensitive to changes in the rotational motion arising from
molecular association or dissociation, ACE-LIFP is capable of providing
information on the formation of affinity complexes prior to or during CE
separation. Unbound, small fluorescent probes generally have little
fluorescence polarization because of rapid rotation of the molecule in
solution. When the small fluorescent probe is bound to a larger affinity agent,
such as an antibody, the fluorescence polarization (and anisotropy) increases
due to slower motion of the much larger complex molecule in the solution.
Fluorescence polarization results are obtained by simultaneously measuring
fluorescence intensities of vertical and horizontal polarization planes.
Applications of CE-LIFP to both strong and weak binding systems are discussed
with antibody-antigen and DNA-protein binding as examples. For strong affinity
binding, such as between cyclosporine and its antibody, complexes are formed
prior to CE-LIFP analysis. For weaker binding, such as between single-stranded
DNA and its binding protein, the single-stranded DNA binding protein is added
to the CE separation buffer to enhance dynamic formation of affinity complexes.
Both fluorescence polarization (and anisotropy) and mobility shift results are
complementary and are useful for immunoassays and binding studies. N. Ref:: 25
----------------------------------------------------
[71]
TÍTULO / TITLE: - A novel pathway
regulating the mammalian target of rapamycin (mTOR) signaling.
REVISTA
/ JOURNAL: - Biochem Pharmacol 2002 Oct 1;64(7):1071-7.
AUTORES
/ AUTHORS: - Chen J; Fang Y
INSTITUCIÓN
/ INSTITUTION: - Department of Cell and Structural Biology,
University of Illinois at Urbana-Champaign, 601 South Goodwin Avenue, B107,
Urbana, IL 61801, USA. jiechen@uiuc.edu
RESUMEN
/ SUMMARY: - Originally discovered as an anti-fungal
agent, the bacterial macrolide rapamycin is a potent immunosuppressant and a
promising anti-cancer drug. In complex with its cellular receptor, the
FK506-binding protein (FKBP12), rapamycin binds and inhibits the function of the
mammalian target of rapamycin (mTOR). By mediating amino acid sufficiency, mTOR
governs signaling to translational regulation and other cellular functions by
converging with the phosphatidylinositol 3-kinase (PI3K) pathway on downstream
effectors. Whether mTOR receives mitogenic signals in addition to
nutrient-sensing has been an unresolved issue, and the mechanism of action of
rapamycin remained unknown. Our recent findings have revealed a novel link
between mitogenic signals and mTOR via the lipid second messenger phosphatidic
acid (PA), and suggested a role for mTOR in the integration of nutrient and
mitogen signals. A molecular mechanism for rapamycin inhibition of mTOR
signaling is proposed, in which a putative interaction between PA and mTOR is abolished
by rapamycin binding. Collective evidence further implicates the regulation of
the rapamycin-sensitive signaling circuitry by phospholipase D, and potentially
by other upstream regulators such as the conventional protein kinase C, the Rho
and ARF families of small G proteins, and calcium ions. As the mTOR pathway has
been demonstrated to be an important anti-cancer target, the identification of
new components and novel regulatory modes in mTOR signaling will facilitate the
future development of diagnostic and therapeutic strategies. N. Ref:: 67
----------------------------------------------------
[72]
TÍTULO / TITLE: - ATP-binding cassette
transporters and calcineurin inhibitors: potential clinical implications.
REVISTA
/ JOURNAL: - Transplant Proc 2001 May;33(3):2420-1.
AUTORES
/ AUTHORS: - van Gelder T; Klupp J; Sawamoto T;
Christians U; Morris RE
INSTITUCIÓN
/ INSTITUTION: - Department of Internal Medicine (T.vG.),
University Hospital Rotterdam, Rotterdam, The Netherlands. vangelder@INW1.AZR.NL N. Ref:: 17
----------------------------------------------------
[73]
TÍTULO / TITLE: - Recent developments in
inflammatory bowel disease.
REVISTA
/ JOURNAL: - Med Clin North Am 2002 Nov;86(6):1497-523.
AUTORES
/ AUTHORS: - Su C; Lichtenstein GR
INSTITUCIÓN
/ INSTITUTION: - Division of Gastroenterology, Department
of Medicine, Hospital of the University of Pennsylvania, University of
Pennsylvania School of Medicine, Third Floor Ravdin Building, 3400 Spruce
Street, Philadelphia, PA 19104-4283, USA.
RESUMEN
/ SUMMARY: - The evolving medical armamentarium holds
promise for more precise and effective therapies for IBD. The experience with
anti-TNF therapy, particularly infliximab, illustrates the potential efficacy
of therapies targeted at specific mediators or pathways involved in the
pathogenesis. Advances in molecular technology have enabled the development of
novel and potentially effective targeted therapies. Equally important is the
increasing scientific understanding of the pathogenesis of IBD, which will
likely improve the ability to stratify disease and to select therapies based on
genotypic, immunologic, and phenotypic profiles in the future. N. Ref:: 191
----------------------------------------------------
[74]
TÍTULO / TITLE: - FTY720: altered
lymphocyte traffic results in allograft protection.
REVISTA
/ JOURNAL: - Transplantation 2001 Sep 15;72(5):764-9.
AUTORES
/ AUTHORS: - Brinkmann V; Pinschewer DD; Feng L; Chen S
INSTITUCIÓN
/ INSTITUTION: - Novartis Pharma AG, Transplantation
Research, WSJ-386.1.01, CH-4002 Basel, Switzerland. N. Ref:: 52
----------------------------------------------------
[75]
TÍTULO / TITLE: - Neonatal toxic shock
syndrome-like exanthematous disease (NTED).
REVISTA
/ JOURNAL: - Pediatr Int 2003 Apr;45(2):233-7.
AUTORES
/ AUTHORS: - Takahashi N
INSTITUCIÓN
/ INSTITUTION: - Department of Pediatrics, Jichi Medical
School, Tochigi-ken, Tokyo Women’s Medical University, Tokyo, Japan. naoto-t@jichi.ac.jp
RESUMEN
/ SUMMARY: - The author and colleagues recently
discovered an emerging neonatal infectious disease: neonatal toxic shock
syndrome-like exanthematous disease (NTED), which is induced by the
superantigen toxic shock syndrome toxin-1 (TSST-1), produced by
methicillin-resistant Staphylococcus aureus (MRSA). The massively expanded
Vbeta2+ T cells were rapidly deleted in the peripheral blood of patients with
NTED. A marked depletion of Vbeta2+ T cells was also observed in the peripheral
blood before the expansion of these T cells. Anergy is specifically induced in
the TSST-1 reactive T cells of patients with NTED. Rapid recovery from NTED
without complications is expected to be related to the induction of immunologic
tolerance in neonatal patients. Anti-TSST-1 IgG antibody of maternal origin was
found to play a protective role in preventing the development of NTED. The
number of hospitals that have experience caring for patients with NTED has
increased threefold in the past 5 years. Most MRSA isolates from neonatal
intensive care units in Japan were found to be a single clone of coagulase type
II and to possess TSST-1 and staphylococcal enterotoxin C genes. The timing and
increased incidence of NTED suggest the emergence of a new MRSA clone. By
recognizing that TSST-1 can induce NTED, healthcare providers may give
increased attention to this disease in neonatal wards. N. Ref:: 43
----------------------------------------------------
[76]
TÍTULO / TITLE: - Basiliximab: a review of
its use as induction therapy in renal transplantation.
REVISTA
/ JOURNAL: - Drugs 2003;63(24):2803-35.
AUTORES
/ AUTHORS: - Chapman TM; Keating GM
INSTITUCIÓN
/ INSTITUTION: - Adis International Limited, Auckland, New
Zealand. demail@adis.co.nz
RESUMEN
/ SUMMARY: - Basiliximab (Simulect), a chimeric
(human/murine) monoclonal antibody, is indicated for the prevention of acute
organ rejection in adult and paediatric renal transplant recipients in
combination with other immunosuppressive agents.Basiliximab significantly
reduced acute rejection compared with placebo in renal transplant recipients
receiving dual- (cyclosporin microemulsion and corticosteroids) or
triple-immunotherapy (azathioprine- or mycophenolate mofetil-based); graft and
patient survival rates at 12 months were similar. Significantly more
basiliximab than placebo recipients were free from the combined endpoint of
death, graft loss or acute rejection 3 years, but not 5 years, after
transplantation.The incidence of adverse events was similar in basiliximab and
placebo recipients, with no increase in the incidence of infection, including
cytomegalovirus (CMV) infection. Malignancies or post-transplant
lymphoproliferative disorders after treatment with basiliximab were rare, with
a similar incidence to that seen with placebo at 12 months or 5 years
post-transplantation. Rare cases of hypersensitivity reactions to basiliximab
have been reported.The efficacy of basiliximab was similar to that of equine antithymocyte
globulin (ATG) and daclizumab, and similar to or greater than that of muromonab
CD3. Basiliximab was as effective as rabbit antithymocyte globulin (RATG) in
patients at relatively low risk of acute rejection, but less effective in
high-risk patients. Numerically or significantly fewer patients receiving
basiliximab experienced adverse events considered to be related to the study
drug than ATG or RATG recipients. The incidence of infection, including CMV
infection, was similar with basiliximab and ATG or RATG.Basiliximab plus
baseline immunosuppression resulted in no significant differences in acute
rejection rates compared with baseline immunosuppression with or without ATG or
antilymphocyte globulin in retrospective analyses conducted for small numbers
of paediatric patients. Limited data from paediatric renal transplant
recipients suggest a similar tolerability profile to that in adults.
Basiliximab appears to allow the withdrawal of corticosteroids or the use of
corticosteroid-free or calcineurin inhibitor-sparing regimens in renal
transplant recipients.Basiliximab did not increase the overall costs of therapy
in pharmacoeconomic studies.CONCLUSION: Basiliximab reduces acute rejection
without increasing the incidence of adverse events, including infection and
malignancy, in renal transplant recipients when combined with standard dual- or
triple-immunotherapy. The overall incidence of death, graft loss or acute
rejection was significantly reduced at 3 years; there was no significant
difference for this endpoint 5 years after transplantation. Malignancy was not
increased at 5 years. The overall efficacy, tolerability, ease of
administration and cost effectiveness of basiliximab make it an attractive
option for the prophylaxis of acute renal transplant rejection. N. Ref:: 85
----------------------------------------------------
[77]
TÍTULO / TITLE: - Pharmacokinetics of
tacrolimus-based combination therapies.
REVISTA
/ JOURNAL: - Nephrol Dial Transplant. Acceso gratuito
al texto completo a partir de los 2 años de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://ndt.oupjournals.org/
●●
Cita: Nephrology Dialysis Transplantation: <> 2003 May;18 Suppl 1:i12-5.
AUTORES
/ AUTHORS: - Undre NA
INSTITUCIÓN
/ INSTITUTION: - Fujisawa GmbH, Neumarkter Str. 61, D-81673
Munich, Germany. nas.undre@fujisawa.de
RESUMEN
/ SUMMARY: - This paper reviews the pharmacokinetics of
tacrolimus, with special reference to its combination with adjunctive
immunosuppressants. Oral bioavailability of tacrolimus, which is variable
between patients, averages approximately 25%. This is largely due to
extrahepatic metabolism of tacrolimus in the gastrointestinal epithelium.
Nevertheless, intra-patient variability is low, as evidenced by the small
number of dose changes required to maintain patients within the recommended
tacrolimus target levels. Tacrolimus is distributed extensively in the body
with most partitioned outside the blood compartment. Concentrations of
tacrolimus in blood are used as a surrogate marker of clinically relevant
concentration of the drug at the site(s) of action. Convenient whole-blood
sampling within a +/-2-h window around 12 h post-dose (C(min)) is highly
predictive of systemic exposure to tacrolimus and is thus used to optimise
therapy. Sampling at other time-points offers no advantage over C(min)
monitoring. The interactions of tacrolimus with other immunosuppressive agents
are well characterized. After cessation of concomitant corticosteroid
treatment, exposure to tacrolimus increases by approximately 25%. In contrast,
there is no pharmacokinetic interaction between mycophenolate mofetil (MMF) and
tacrolimus. Therefore, systemic exposure to the active metabolite of MMF,
mycophenolic acid, is higher with MMF-tacrolimus combination than with
MMF-cyclosporin combination. Therefore, 1 g/day MMF may be an adequate
maintenance dose in tacrolimus-based regimens. Co-administration of tacrolimus
and sirolimus, while having no effect on exposure to sirolimus, results in
reduced exposure to tacrolimus at sirolimus doses of 2 mg/day and above. In
conclusion, tacrolimus levels should be monitored when sirolimus is
co-administered at doses >2 mg/day and after cessation of corticosteroid
treatment. N. Ref:: 13
----------------------------------------------------
[78]
- Castellano -
TÍTULO / TITLE:La enfermedad linfoproliferativa
difusa postrasplante renal y su relacion con el virus Epstein-Barr. Experiencia
de un centro. Diffuse lymphoproliferative disease after renal transplantation
and its relation with Epstein-Barr virus. Experience at one center.
REVISTA
/ JOURNAL: - Nefrologia. Acceso gratuito al texto
completo.
●●
Enlace a la Editora de la Revista http://www.aulamedica.es/nefrologia/
●●
Cita: Nefrologia: <> 2002;22(5):463-9.
AUTORES
/ AUTHORS: - Franco A; Jimenez L; Aranda I; Alvarez L;
Gonzalez M; Rocamora N; Olivares J
INSTITUCIÓN
/ INSTITUTION: - Servicio de Nefrologia Hospital General
Alicante Maestro Alonso, 109 03010 Alicante. franco_ant@gva.es
RESUMEN
/ SUMMARY: - Post-transplant lymphoproliferative disorders
(PTLD) are a group of heterogeneous lymphoid proliferations in chronic
immunosuppressed recipients which appear to be related to Epstein Barr Virus
(EBV). Receptor EBV seronegativity, use of antilymphocyte antibodies and CMV
disease have been identified as risk factors that may tigger development of
PTLD. We have studied the incidence of PTLD and its relationship with EBV in
588 adult renal transplant recipients who were transplanted in our hospital
from 1988 to 2001. We have also evaluated the diagnostic and therapeutic
methods used, the risk factors and outcome of the patients who developed PTLD.
We identified 8 recipients (4 males and 4 females), range from 18 to 67 years
(mean age 45.6 years) with a median time between grafting and PTLD of 4.1 years
(0.1-7 years), who developed PTLD (1.3%). Only 1 patient received OKT3 and had
CMV disease, two of them (25%) had been treated with hight doses of
prednisolone, another was EBV seronegative, but the rest of them (50%) had no
risk factors. Two patients were diagnosed at autopsy, the diagnosis of 5 was
based on the histology of biopsy and the last one by CT scans of chest-abdomen
and cytology. The presence of EBV in the lymphoproliferative cells was assessed
in 5 out of the 7 studied patients (71.4%). The outcome of our recipients was
poor. Five out of 8 patients died shortly after diagnosis as a direct
consecuence of PTLD and another of an infectious complication of the treatment
(75%). The 2 patients alive started dialysis and 1 of them died 2 years later of
a non-related cause. In conclusion, PTLD is a relatively frequent disease with
a poor prognosis in renal transplant patients. It seems to have a close
relationship with EBV and can develop in the absence of the classical risk
factors. N. Ref:: 18
----------------------------------------------------
[79]
TÍTULO / TITLE: - TOR action in mammalian
cells and in Caenorhabditis elegans.
REVISTA
/ JOURNAL: - Curr Top Microbiol Immunol
2004;279:115-38.
AUTORES
/ AUTHORS: - Long X; Muller F; Avruch J
INSTITUCIÓN
/ INSTITUTION: - Diabetes Research Laboratory, Department
of Molecular Biology, Land Medicine Massachusetts General Hospital, Boston, MA
02114, USA.
RESUMEN
/ SUMMARY: - The p70 S6 kinase (p70 S6K) was the first
signaling element in mammalian cells shown to be inhibited by rapamycin. The
activity of the p70 S6K in mammalian cell is upregulated by extracellular amino
acids (especially leucine) and by signals from receptor tyrosine kinases
(RTKs), primarily through activation of the type 1A PI-3 kinase. The amino
acid-/rapamycin-sensitive input and the PI-3 kinase input are co-dominant but
largely independent, in that deletion of the amino-terminal and
carboxy-terminal noncatalytic sequences flanking the p70 S6K catalytic domain
renders the kinase insensitive to inhibition by both rapamycin and by
withdrawal of amino acids, whereas this p70 S6K mutant remains responsive to
activation by RTKs and to inhibition by wortmannin. At a molecular level, this
dual control of p70 S6K activity is attributable to phosphorylation of the two
p70 S6K sites: The Ptd Ins 3,4,5P3-dependent kinasel (PDK1) phosphorylates p70
S6K at a Thr on the activation loop, whereas mTOR phosphorylates a Thr located
in a hydrophobic motif carboxyterminal to the catalytic domain. Together these
two phosphorylations engender a strong, positively cooperative activation of
p70 S6K, so that each is indispensable for physiologic regulation. Like RTKs,
the p70 S6K appears early in metazoan evolution and comes to represent an
important site at which the more ancient, nutrient-responsive TOR pathway
converges with the RTK/PI-3 kinase pathway in the control of cell growth. Dual
regulation of p70 S6K is seen in Drosophila; however, this convergence is not
yet evident in Caenorhabditis elegans, wherein nutrient activation of the
insulin receptor (InsR) pathway negatively regulates dauer development and
longevity, whereas the TOR pathway regulates overall mRNA translation through
effectors distinct from p70 S6K, as in yeast. The C. elegans TOR and InsR pathways
show none of the cross- or convergent regulation seen in mammalian cells. The
nature of the elements that couple nutrient sufficiency to TOR activity remain
to be discovered, and the mechanisms by which RTKs influence TOR activity in
mammalian cells require further study. One pathway for RTK control involves the
tuberous sclerosis complex, which is absent in C. elegans, but of major
importance in Drosophila and higher metazoans.
N. Ref:: 98
----------------------------------------------------
[80]
TÍTULO / TITLE: - Primary intestinal
posttransplant T-cell lymphoma.
REVISTA
/ JOURNAL: - Transplantation 2003 Jun 27;75(12):2131-2.
●●
Enlace al texto completo (gratuito o de pago) 1097/01.TP.0000060253.54333.F3
AUTORES
/ AUTHORS: - Michael J; Greenstein S; Schechner R;
Tellis V; Vasovic LV; Ratech H; Glicklich D
INSTITUCIÓN
/ INSTITUTION: - Division of Nephrology, Albert Einstein
College of Medicine, Montefiore Medical Center, Bronx, New York 10467, USA.
RESUMEN
/ SUMMARY: - There have been only five reported cases
of primary posttransplant T-cell lymphoma. We report the first case associated
with the use of sirolimus (Rapamycin, Wyeth-Ayerst, Philadelphia, PA). The
patient, receiving prednisone, cyclosporine, and sirolimus treatment, developed
ascites, diarrhea, and weight loss 7 months after his second renal transplant.
Tissue obtained at laparotomy established the diagnosis of primary T-cell
lymphoma. Latent membrane protein-1 for Epstein-Barr virus was negative, but
in-site hybridization test for Epstein-Barr-encoded RNA was positive. Despite
aggressive chemotherapy, the patient died 8 months posttransplant. This is the
sixth reported case of primary intestinal posttransplant T-cell lymphoma, but
it is the first case associated with the use of sirolimus. The incidence of
posttransplant lymphoproliferative disease in patients receiving sirolimus
should be studied. N.
Ref:: 6
----------------------------------------------------
[81]
- Castellano -
TÍTULO / TITLE:Alteraciones del metabolismo oseo
tras el trasplante renal. Bone metabolism alterations after kidney transplantation.
REVISTA
/ JOURNAL: - Nefrologia. Acceso gratuito al texto
completo.
●●
Enlace a la Editora de la Revista http://www.aulamedica.es/nefrologia/
●●
Cita: Nefrologia: <> 2003;23 Suppl 2:122-6.
AUTORES
/ AUTHORS: - Torres A; Garcia S; Barrios Y; Hernandez
D; Lorenzo V
INSTITUCIÓN
/ INSTITUTION: - Servicio de Nefrologia, Unidad de
Investigacion, Hospital Universitario de Canarias, Instituto Reina Sofia de
Investigacion. atorres@ull.es
RESUMEN
/ SUMMARY: - Early after renal transplantation (RT) a
rapid decrease in bone mineral density at the lumbar spine, femoral neck, and
femoral shaft has been documented. In addition, an appreciable proportion of
patients still remain losing bone late after RT. As a consequence, RT patients
are at a high risk of bone fractures as compared to general population. Most
fractures involve appendicular skeleton, particularly the feet and ankles, and
the diabetic patient is at increased risk of fractures. Thus, early institution
of preventive measures and treatment of established osteoporosis are central.
The major cause of post-transplantation bone loss is corticosteroid treatment,
and this should be used at the lower dose compatible with graft survival.
Preexisting hyperparathyroidism also affects the early cancellous bone loss at
the spine, and post-transplantation bone loss reflects variable individual
susceptibility, resembling the polygenic determination of bone mineral density
in general. Clinical trials have demonstrated that bisphosphonates or vitamin D
plus calcium supplementation, prevent post-transplantation bone loss during the
first 6-12 months. However, their role in preventing bone fractures has not
been proven. Finally, recommendations for management, prevention and treatment,
are summarized. N.
Ref:: 24
----------------------------------------------------
[82]
TÍTULO / TITLE: - Efficacy and toxicity
of a protocol using sirolimus, tacrolimus and daclizumab in a nonhuman primate
renal allotransplant model.
REVISTA
/ JOURNAL: - Am J Transplant 2002 Apr;2(4):381-5.
AUTORES
/ AUTHORS: - Montgomery SP; Mog SR; Xu H; Tadaki DK;
Hirshberg B; Berning JD; Leconte J; Harlan DM; Hale D; Kirk AD
INSTITUCIÓN
/ INSTITUTION: - NIDDK/Navy Transplantation and
Autoimmunity Branch, Naval Medical Research Center, Bethesda, Maryland 20892,
USA.
RESUMEN
/ SUMMARY: - A regimen combining sirolimus, tacrolimus,
and daclizumab has recently been shown to provide adequate immunosuppression
for allogeneic islet transplantation in humans, but remains unproven for primarily
vascularized allografts. We evaluated this regimen for renal allograft
transplantation in mismatched nonhuman primates. Dosages of sirolimus and
tacrolimus were adjusted for trough levels of 10-15 ng/mL and 4-6 ng/mL,
respectively. Treated monkeys (n = 5) had significantly prolonged allograft
survival, with a mean survival of 36 days vs. 7 days in untreated controls (n =
6, p = 0.008). Four of five treated animals, but none of the controls,
developed fibrinoid vascular necrosis of the small intestine. A review of gut
histology from animals on other immunosuppressive protocols performed by our
laboratory suggested that these lesions were a result of sirolimus exposure. In
summary, this regimen prolongs the survival of vascularized renal allografts,
but is limited by profound GI toxicity in rhesus macaques.
----------------------------------------------------
[83]
TÍTULO / TITLE: - Treatment responses of
childhood aplastic anaemia with chromosomal aberrations at diagnosis.
REVISTA
/ JOURNAL: - Br J Haematol 2002 Jul;118(1):313-9.
AUTORES
/ AUTHORS: - Ohga S; Ohara A; Hibi S; Kojima S; Bessho
F; Tsuchiya S; Ohshima Y; Yoshida N; Kashii Y; Nishimura S; Kawakami K;
Nishikawa K; Tsukimoto I
INSTITUCIÓN
/ INSTITUTION: - Aplastic Anaemia Committee of the Japanese
Society of Paediatric Haematology, Tokyo, Japan. ohgas@pediatr.med.kyushu-u.ac.jp
RESUMEN
/ SUMMARY: - The clinical outcome of childhood aplastic
anaemia (AA) with aberrant cytogenetic clones at diagnosis was surveyed. Among
198 children with newly diagnosed AA registered with the AA Committee of the
Japanese Society of Paediatric Hematology between 1994 and 1998, cytogenetic
studies of bone marrow (BM) cells were completed in 159 patients. Apart from
one Robertsonian translocation, seven patients (4.4%) showed clonal chromosomal
abnormalities in hypoplastic BM without myelodysplastic features. The patients
included six girls and one boy with a median age of 11 years (range 5-14
years). Six patients had del(6), del(5), del(13), del(20), or -7, and one
showed add(9). Four patients responded to the first immunosuppressive therapy
(IST: cyclosporin A plus anti-thymocyte globulin) and one obtained a
spontaneous remission. Cytogenetic abnormalities remained in two patients with
an IST response. On the other hand, two patients showed no IST response. One
did not respond to repeat IST and died of acute graft-versus-host disease after
an unrelated-BM transplant. Another obtained a complete response after a
successful BM transplant. No haematological findings at diagnosis predicted the
treatment response. No significant morphological changes developed during the
course of the illness. A literature review revealed that half of 24 AA patients
with chromosomal abnormalities responded to the first IST, and that +6 was the
sole predictable marker for IST unresponsiveness. These results suggest that
IST can be applied as the initial therapy for AA with cytogenetic abnormalities
in the absence of completely matched donors.
N. Ref:: 32
----------------------------------------------------
[84]
TÍTULO / TITLE: - Acute necrotizing
gastritis by Escherichia coli in a severely neutropenic patient.
REVISTA
/ JOURNAL: - Haematologica. Acceso gratuito al texto
completo.
●●
Enlace a la Editora de la Revista http://db.doyma.es/
●●
Cita: Haematologica: <> 2002 Jan;87(1):ELT01.
AUTORES
/ AUTHORS: - Martinez-Chamorro C; Martinez E;
Gil-Fernandez JJ; Escudero A; Acevedo A; Fernandez-Ranada JM
INSTITUCIÓN
/ INSTITUTION: - Hematology Department, Clinica Ruber,
C/Juan Bravo, 49 28006-Madrid, España. m-chamorro@navegalia.com N. Ref:: 6
----------------------------------------------------
[85]
TÍTULO / TITLE: - Treatment of membranous
nephropathy.
REVISTA
/ JOURNAL: - Nephrol Dial Transplant. Acceso gratuito
al texto completo a partir de los 2 años de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://ndt.oupjournals.org/
●●
Cita: Nephrology Dialysis Transplantation: <> 2001;16 Suppl 5:8-10.
AUTORES
/ AUTHORS: - Ponticelli C; Passerini P
INSTITUCIÓN
/ INSTITUTION: - Division of Nephrology, Ospedale Maggiore
di Milano, Italy.
RESUMEN
/ SUMMARY: - Several therapeutic approaches have been
tried in patients with membranous nephropathy. Corticosteroids have been
largely used, but a meta-analysis of the available controlled trials did not
show any benefit of corticosteroids either in favouring remission of the
nephrotic syndrome or in preventing renal dysfunction. Controversial results
have been obtained with cytotoxic agents. Unfortunately, most of the available
trials were small in size and had short-term follow-ups. Three controlled
trials evaluated the role of a 6-month treatment with methylprednisolone and
chlorambucil. The first trial showed that the 10-year renal survival rate was
92% in treated patients compared with 60% in untreated controls. A second trial
compared the effects of methylprednisolone/chlorambucil with those of
methylprednisolone alone. The combined treatment achieved remission of
nephrotic syndrome in 64% of cases vs 38% in patients given steroids alone. A
third trial showed equivalent results in patients randomized to be given
methylprednisolone/chlorambucil or methylprednisolone/cyclophosphamide. A
number of non-controlled studies and a randomized trial also showed the
efficacy of cyclosporine in reducing proteinuria. In many but not all cases,
proteinuria reappeared when cyclosporine was stopped. In conclusion, although
the treatment of membranous nephropathy remains difficult, some therapeutical
approaches have proved to favour remission and protect renal function N. Ref:: 53
----------------------------------------------------
[86]
TÍTULO / TITLE: - Inhibitors of mammalian
target of rapamycin as novel antitumor agents: from bench to clinic.
REVISTA
/ JOURNAL: - Curr Opin Investig Drugs 2002
Feb;3(2):295-304.
AUTORES
/ AUTHORS: - Huang S; Houghton PJ
INSTITUCIÓN
/ INSTITUTION: - Department of Molecular Pharmacology, St
Jude Children’s Research Hospital, Memphis, TN 38105-2794, USA.
RESUMEN
/ SUMMARY: - Rapamycin and its derivatives, CCI-779 and
RAD-001, inhibit the mammalian target of rapamycin (mTOR), downregulating
translation of specific mRNAs required for cell cycle progression from G1 to S
phase. Preclinically, mTOR inhibitors potently suppress growth and
proliferation of numerous tumor cell lines in culture or when grown in mice as
xenografts. CCI-779 and RAD-001 are being developed as antitumor drugs and are
undergoing clinical trials. Clinically, CCI-779 has shown evidence of antitumor
activity but induced relatively mild side effects in patients. Here we discuss
potential antitumor mechanisms and resistance mechanisms of mTOR inhibitors,
and summarize the current status of these compounds as novel antitumor
agents. N. Ref:: 90
----------------------------------------------------
[87]
TÍTULO / TITLE: - Regulation of
translation via TOR signaling: insights from Drosophila melanogaster.
REVISTA
/ JOURNAL: - J Nutr. Acceso gratuito al texto completo
a partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.nutrition.org/
●●
Cita: Journal of Nutrition: <> 2001 Nov;131(11):2988S-93S.
AUTORES
/ AUTHORS: - Miron M; Sonenberg N
INSTITUCIÓN
/ INSTITUTION: - Department of Biochemistry and McGill
Cancer Center, McGill University, Montreal, Quebec, Canada.
RESUMEN
/ SUMMARY: - The target of rapamycin (TOR) proteins are
large protein kinases evolutionarily conserved from yeast to human. A large
body of evidence demonstrates that TOR proteins function in a nutrient-sensing
checkpoint whose role is to restrict growth under conditions of low nutrient
availability. Under such conditions, TOR blocks the transmission of
growth-promoting signals from extracellular stimuli. Recent data obtained by
genetic studies in the fruit fly Drosophila melanogaster demonstrate the
importance of both insulin-like signaling and TOR signaling in promoting
growth. Importantly, these studies identified a major downstream target of TOR
and insulin-like signaling as the translational machinery. N. Ref:: 63
----------------------------------------------------
[88]
TÍTULO / TITLE: - Treatment of severe
acute graft-versus-host disease with anti-thymocyte globulin.
REVISTA
/ JOURNAL: - Clin Transplant 2001 Jun;15(3):147-53.
AUTORES
/ AUTHORS: - Remberger M; Aschan J; Barkholt L;
Tollemar J; Ringden O
INSTITUCIÓN
/ INSTITUTION: - Department of Clinical Immunology and
Centre for Allogeneic Stem Cell Transplantation, Karolinska Institutet,
Huddinge University Hospital, Stockholm, Sweden. mats.remberger@impi.ki.se
RESUMEN
/ SUMMARY: - Severe acute graft-versus-host disease
(GVHD) is one of the major complications after haematopoietic stem-cell
transplantation (HSCT). Treatment of severe GVHD is difficult and the condition
is often fatal. One proposed method of improving the therapy is to include
anti-thymocyte globulin (ATG). Here, we will report our results in 29 patients
using ATG as part of treatment for severe steroid-resistant acute GVHD. Four
patients suffered from grade II, 13 from grade III and 12 from grade IV GVHD.
Median time to grade II GVHD was 24 d (range 7-91 d) and to grade III was 29 d
(range 8-55 d) after HSCT. Five different ATG preparations were used, rabbit
ATG (R-ATG), BMA 031, OKT3, ATG-Fresenius and Thymoglobuline. All patients had
skin involvement, 26 also had gut involvement and 25 had liver involvement. The
rate of response to treatment was best in skin involvement (72%), while liver
and gut involvement showed lower response rates (38%). Eleven patients survived
more than 90 d, 7 of them developed chronic GVHD, 1 developed mild GVHD, 1
developed moderate GVHD and 5 developed severe GVHD. Survival at 100 d was 37%
and at 1 yr it was 12%. Most patients died of GVHD, with virus or fungal
infections as contributing causes of death. To conclude, treatment of severe
acute GVHD is difficult and ATG, in our hands, adds nothing to conventional
pharmacological treatment. N.
Ref:: 48
----------------------------------------------------
[89]
TÍTULO / TITLE: - Mitochondrial
involvement in the point of no return in neuronal apoptosis.
REVISTA
/ JOURNAL: - Biochimie 2002 Feb-Mar;84(2-3):223-31.
AUTORES
/ AUTHORS: - Chang LK; Putcha GV; Deshmukh M; Johnson
EM Jr
INSTITUCIÓN
/ INSTITUTION: - Department of Neurology, Washington
University School of Medicine, 660 South Euclid Avenue, Campus Box 8103, St.
Louis, MO 63110-1031, USA.
RESUMEN
/ SUMMARY: - Programmed cell death (PCD) contributes to
development, maintenance, and pathology in various tissues, including the
nervous system. Many molecular, biochemical, and genetic events occur within
cells undergoing PCD. Some of these events are incompatible with long-term cell
survival because they have irreversible, catastrophic consequences. The onset
of such changes marks the point of no return, a decisive regulatory event
termed ‘the commitment-to-die.’ In this review, we discuss events that underlie
the commitment-to-die in nerve growth factor-deprivation-induced death of
sympathetic neurons. Findings in this model system implicate the mitochondrion
as an important site of regulation for the commitment-to-die in the presence or
absence of caspase inhibition. N.
Ref:: 57
----------------------------------------------------
[90]
TÍTULO / TITLE: - First human double hand
transplantation: efficacy of a conventional immunosuppressive protocol.
REVISTA
/ JOURNAL: - Clin Transplant 2003 Oct;17(5):455-60.
AUTORES
/ AUTHORS: - Petruzzo P; Revillard JP; Kanitakis J;
Lanzetta M; Hakim NS; Lefrancois N; Owen E; Dubernard JM
INSTITUCIÓN
/ INSTITUTION: - Service de Chirurgie de Transplantation,
Hopital Edouard Herriot, Lyon, France.
RESUMEN
/ SUMMARY: - Based on the results achieved in single
human hand transplantations, we decided to perform the first double hand
transplantation with a conventional immunosuppressive protocol in a patient
with a high potential for functional recovery. Two years after transplantation
the efficacy and the safety of this immunosuppressive protocol are evaluated.
The recipient was a 33-yr-old man suffering from a traumatic amputation of both
hands in 1996. Five HLA-A, -B, and -DR mismatches were present with the donor;
T and B cell cross-match was negative. Immunosuppressive protocol included
tacrolimus, prednisone, mycophenolate mofetil and, for induction, antithymocyte
globulins and then anti CD25 monoclonal antibody. Reconstitution of lymphocyte
populations proceeded normally. Neither anti-HLA antibodies nor chimerism in
peripheral blood were detected. Two episodes of acute rejection characterized
by maculopapular lesions occurred on days 53 and 82 after transplantation. Skin
biopsies revealed a dermal lymphocytic infiltrate. Both episodes were
completely and rapidly reversed by topical clobetasol and increased systemic
corticosteroid therapy. The only side-effects related to treatment were
reversible serum sickness and hyperglycemia. No infectious complications and
malignancies occurred. No signs of graft-versus-host disease have been
detected. This case of double hand transplantation shows that conventional
immunosuppression is effective and safe to ensure survival and functional
recovery of the grafted limb.
----------------------------------------------------
[91]
TÍTULO / TITLE: - Mechanisms and
consequences of arterial hypertension after renal transplantation.
REVISTA
/ JOURNAL: - Transplantation 2001 Sep 27;72(6
Suppl):S9-12.
AUTORES
/ AUTHORS: - Koomans HA; Ligtenberg G
INSTITUCIÓN
/ INSTITUTION: - Department of Nephrology and Hypertension,
University Hospital Utrecht, The Netherlands. h.a.koomans@digd.azu.nl
RESUMEN
/ SUMMARY: - The high incidence of hypertension after
renal transplantation contributes to the risk of cardiovascular morbidity and
mortality in renal transplant recipients. Although cyclosporine has been
influential in the improvement of transplant outcome, it has emerged as a major
cause of hypertension after organ transplantation. The underlying
pathophysiological mechanisms of cyclosporine-induced hypertension include
enhanced sympathetic nervous system activity, renal vasoconstriction, and
sodium/water retention. Hypertension is also significantly associated with
reduced graft survival and thereby requires aggressive treatment intervention.
Calcium channel blockers may offer some advantages over angiotensin-converting
enzyme inhibitors for the treatment of hypertension in stable renal transplant
recipients. Nevertheless, selection of the most appropriate antihypertensive
agent should take into account the possibility of pharmacokinetic interactions
with immunosuppressive agents. There is evidence to suggest that the use of
tacrolimus-based immunosuppression induces less hypertension compared with
cyclosporine. Not only do patients receiving tacrolimus tend to require less
antihypertensive therapy, but converting patients from cyclosporine to
tacrolimus has been shown to result in significant reductions in blood
pressure. Thus, tacrolimus may be associated with an improved cardiovascular
risk profile in renal transplant recipients.
N. Ref:: 26
----------------------------------------------------
[92]
TÍTULO / TITLE: - T-cell receptor-derived
peptides in immunoregulation and therapy of retrovirally induced immunosuppression.
REVISTA
/ JOURNAL: - Crit Rev Immunol 2001;21(1-3):57-74.
AUTORES
/ AUTHORS: - Marchalonis JJ; Robey IF; Edmundson AB;
Sepulveda RT; Watson RR
INSTITUCIÓN
/ INSTITUTION: - Microbiology and Immunology, College of
Medicine, University of Arizona, Tucson 85724, USA. dianah@u.arizona.edu
RESUMEN
/ SUMMARY: - Retrovirally infected humans and mice
showed progressive acquired immunodeficiency accompanied by the production of
elevated levels of autoantibodies directed against T-cell receptor
variable-domain epitopes. Epitope mapping analyses indicated that a major
determinant recognized was defined by a 16-mer peptide containing the entire
CDR1 segment and part of the FR2 region of human Vbeta8, and that both species
showed reactivity to the same sequence. Either prophylactic or therapeutic
administration of this peptide to retrovirus-infected C57/BL/6 mice normalized
the balance of T(H)1- and T(H)2-type helper activity and restored the
resistance to infection by the opportunistic parasite Cryptosporidium.
Administration of the peptide did not generate significantly increased levels
of autoantibody, but had a profound effect on T-cell activity as well as other
aspects of inflammation, including NK-cell activity. A 16-mer derived from the
Jbeta sequence showed similar functional effects on T cells from
retrovirus-infected mice. Direct binding of the VbetaCDR1 peptide to
recombinant TCR Valpha/Vbeta constructs, as well as to IgM natural
autoantibodies, suggests that the cell surface receptor for the peptide is the
alpha/beta TCR on T cells and surface IgM in B cells. The Vbeta CDR1 peptide
stimulated division of murine splenocytes in vitro, stimulated the production
of the T(H)1 cytokine IL-2, and synergized with the T-cell mitogen concanavalin
A in proliferation and IL-2 production. These studies indicate that
administration of peptides derived from T-cell receptor variable domains to
animals immunosuppressed as a result of retroviral infection has a profound immunomodulatory
effect enhancing overall T-cell functional capacity, particularly with respect
to the cytokine production characteristic of T(H)1-type cells. Our studies are
interpreted in the context of other recent investigations of immunomodulatory
peptides. N. Ref:: 69
----------------------------------------------------
[93]
TÍTULO / TITLE: - Current and future
applications of immunological attenuation via pegylation of cells and tissue.
REVISTA
/ JOURNAL: - BioDrugs 2001;15(12):833-47.
AUTORES
/ AUTHORS: - Chen AM; Scott MD
INSTITUCIÓN
/ INSTITUTION: - Center for Immunology and Microbial
Disease, Albany Medical College, Albany, New York, USA.
RESUMEN
/ SUMMARY: - Prevention of immunological rejection of
transplanted tissues is of crucial importance in transplantation medicine.
Current procedures primarily use pharmacological agents such as cyclosporin,
which, while effective, must be typically administered for the life of the
individual. Furthermore, the drug-induced global immunosuppression of the
patient predisposes the individual to infection and enhances their risk of
developing certain forms of cancer. Hence, additional methods are needed to
both enhance tissue engraftment and diminish the adverse effects of current
immunosuppressive therapy. Studies from blood transfusion (i.e. a specialised
form of cellular transplantation) suggest that covalent modification of cells
and tissues with methoxypoly(ethylene glycol) [mPEG] can significantly diminish
rejection episodes and may further enhance the induction of tolerance to donor
tissues. The mechanisms underlying mPEG-mediated immunocamouflage are the loss
of antigen recognition, impaired cell-cell interaction, and an inability of
endogenous antibodies (e.g. immunoglobulin G) to effectively recognise and bind
foreign epitopes. As a consequence of the global camouflage imparted by mPEG,
the weak co-stimulation of alloreactive T cells may subsequently induce
apoptosis, thus leading to tolerance. Initial studies on the transplantation of
pegylated isogeneic rat pancreatic islets demonstrates that mPEG-derivatisation
does not impair in vivo cellular signalling and function. Thus, in contrast to
the pharmacological inhibition of the recipient’s immune response, the
mPEG-mediated immunocamouflage directly addresses the inherent antigenicity and
immunogenicity of the donor tissue itself while leaving the recipient a fully
competent immune system. N.
Ref:: 43
----------------------------------------------------
[94]
TÍTULO / TITLE: - P-glycoprotein in acute
myeloid leukaemia: therapeutic implications of its association with both a
multidrug-resistant and an apoptosis-resistant phenotype.
REVISTA
/ JOURNAL: - Leuk Lymphoma 2002 Jun;43(6):1221-8.
AUTORES
/ AUTHORS: - Pallis M; Turzanski J; Higashi Y; Russell
N
INSTITUCIÓN
/ INSTITUTION: - Academic Haematology, Nottingham City
Hospital, Nottingham, UK. monica.pallis@nottingham.ac.uk
RESUMEN
/ SUMMARY: - P-glycoprotein (Pgp) expression is an
independent prognostic factor for response to remission-induction chemotherapy
in acute myeloblastic leukaemia, particularly in the elderly. There are several
potential agents for modulating Pgp-mediated multi-drug resistance, such as
cyclosporin A and PSC833, which are currently being evaluated in clinical
trials. An alternative therapeutic strategy is to increase the use of drugs
which are unaffected by Pgp. However, in this review, we explain why this may
be more difficult than it appears. Evidence from in vitro studies of primary
AML blasts supports the commonly held supposition that chemoresistance may be
linked to apoptosis-resistance. We have found that Pgp has a drug-independent
role in the inhibition of in vitro apoptosis in AML blasts. Modulation of
cytokine efflux, signalling lipids and intracellular pH have all been suggested
as ways by which Pgp may affect cellular resistance to apoptosis; these are
discussed in this review. For a chemosensitising agent to be successful, it may
be more important for it to enhance apoptosis than to increase drug
uptake. N. Ref:: 95
----------------------------------------------------
[95]
TÍTULO / TITLE: - The potential of
antibody-based immunosuppressive agents for corneal transplantation.
REVISTA
/ JOURNAL: - Immunol Cell Biol 2003 Apr;81(2):93-105.
AUTORES
/ AUTHORS: - Thiel MA; Coster DJ; Williams KA
INSTITUCIÓN
/ INSTITUTION: - Department of Ophthalmology, Flinders
University of South Australia, Adelaide, Australia.
RESUMEN
/ SUMMARY: - Corneal transplantation is a sight-restorative
procedure but its success is limited by irreversible graft rejection, which
accounts for up to 50 per cent of failures. The normal eye is an
immune-privileged site. Multiple mechanisms maintain ocular privilege,
including the blood-eye barrier, the lack of blood vessels and lymphatics in
the normal cornea, the relative paucity of mature antigen-presenting cells in
the central cornea, the presence of immunomodulatory factors in ocular fluids,
and the constitutive expressive of CD95L (Fas ligand) within the eye. However,
privilege can be eroded by the sequelae of inflammation and neovascularization.
Corneal graft rejection in humans is currently suppressed with topical
glucocorticosteroids, which are moderately effective. Systemically administered
immunosuppressive therapy is of limited efficacy and may be accompanied by
unacceptable morbidity. Alternative therapies are needed to improve outcomes.
Corneal graft rejection is primarily a cell-mediated response controlled by the
CD4+ T cell, and thus CD4 and costimulatory molecule blockade are appealing
targets for new therapeutic interventions. A number of monoclonal antibodies
have shown promise as immunosuppressants to prolong corneal graft survival in
experimental animal models, and may eventually prove to be useful adjuncts to
corticosteroids. N.
Ref:: 205
----------------------------------------------------
[96]
TÍTULO / TITLE: - Effective prophylactic
protocol in delayed hypersensitivity to contrast media: report of a case
involving lymphocyte transformation studies with different compounds.
REVISTA
/ JOURNAL: - Radiology. Acceso gratuito al texto
completo a partir de los 2 años de la publicación; - http://radiology.rsnajnls.org/
●●
Cita: Radiology: <> 2002 Nov;225(2):466-70.
AUTORES
/ AUTHORS: - Romano A; Artesani MC; Andriolo M; Viola
M; Pettinato R; Vecchioli-Scaldazza A
INSTITUCIÓN
/ INSTITUTION: - Department of Internal Medicine and
Geriatrics, Universita’ Cattolica del Sacro Cuore, Allergy Unit, Complesso
Integrato Columbus, Via G. Moscati 31, 00168 Rome, Italy. columbus.allerg@linet.it
RESUMEN
/ SUMMARY: - A patient with maculopapular reactions to
iopamidol needed to undergo angiography for a cerebral arteriovenous
malformation. In vivo and in vitro tests were performed with ionic and nonionic
contrast media, including iopamidol and iobitridol. All results were positive,
demonstrating delayed hypersensitivity. The patient received 6-alpha-methylprednisolone
and cyclosporine 1 week before and 2 weeks after four angiograms were obtained
with the use of iobitridol, which was well tolerated.
----------------------------------------------------
[97]
TÍTULO / TITLE: - A pilot protocol of a
calcineurin-inhibitor free regimen for kidney transplant recipients of marginal
donor kidneys or with delayed graft function.
REVISTA
/ JOURNAL: - Clin Transplant 2003;17 Suppl 9:31-4.
AUTORES
/ AUTHORS: - Shaffer D; Langone A; Nylander WA; Goral
S; Kizilisik AT; Helderman JH
INSTITUCIÓN
/ INSTITUTION: - Department of Surgery, Vanderbilt
University Medical Center, Nashville, TN 37232, USA. david.schaffer@vanderbilt.edu
RESUMEN
/ SUMMARY: - The worsening shortage of cadaver donor
kidneys has prompted use of expanded or marginal donor kidneys (MDK), i.e.
older age or donor history of hypertension or diabetes. MDK may be especially
susceptible to calcineurin-inhibitor (CI) mediated vasoconstriction and
nephrotoxicity. Similarly, early use of CI in patients with delayed graft
function may prolong ischaemic injury. We developed a CI-free protocol of
antibody induction, sirolimus, mycophenolate mofetil, and prednisone in
recipients with MDK or DGF. METHODS: Adult renal transplant recipients who
received MDK or had DGF were treated with a CI-free protocol consisting of
antibody induction (basiliximab or thymoglobulin), sirolimus, mycophenolate
mofetil, and prednisone. Serial biopsies were performed for persistent DGF.
Patients were followed prospectively with the primary endpoints being patient
and graft survival, biopsy-proven acute rejection, and sirolimus-related
toxicity. RESULTS: Nineteen recipients were treated. Mean follow-up was 294
days. Actuarial 6- and 12-month patient survival was 100% and 100% and graft
survival was 93% and 93%, respectively. The only graft loss was due to primary
non-function (PNF). The incidence of AR was 16%. Mean serum creatinine at last
follow-up was 1.6 mg/dL. Sirolimus-related toxicity included lymphocele (1),
wound infection (2), thrombocytopenia (1). and interstitial pneumonitis (1).
CONCLUSION: A CI-free protocol with antibody induction and sirolimus results in
low rates of AR and PNF and excellent early patient and graft survival in
patients with MDK and DGF. CI-free protocols may allow expansion of the kidney
donor pool by encouraging utilization of MDK at high risk for DGF or
CI-mediated nephrotoxicity.
----------------------------------------------------
[98]
TÍTULO / TITLE: - Potential role of
immune modulation in the effective long-term control of HIV-1 infection.
REVISTA
/ JOURNAL: - J Biol Regul Homeost Agents 2002
Jan-Mar;16(1):83-90.
AUTORES
/ AUTHORS: - Rizzardi GP; Lazzarin A; Pantaleo G
INSTITUCIÓN
/ INSTITUTION: - MOLMED, Milan, Italy. paolo.rizzardi@molmed.it
RESUMEN
/ SUMMARY: - Recent advances in HIV-1 pathogenesis, and
in defining virological and immunological responses to highly active
antiretroviral therapy (HAART), along with the identification of the numerous
drawbacks of HAART, have clearly demonstrated that the eradication of the virus
is not a feasible therapeutic goal, and that there is an urgent need to develop
other approaches to fight HIV-1 infection. Novel therapeutic approaches of
immune modulation have recently been evaluated in pilot clinical trials. First,
treating primary HIV-1 infection with cyclosporin A (CsA) coupled with HAART to
target massive immune activation extends the benefits achieved with HAART
during primary HIV-1 infection and might contribute to the establishment of a
more favourable immunological set-point affecting the ultimate pattern and rate
of disease progression. Second, treating chronic HIV-1 infection in patients with
long-term suppression of virus replication induced by HAART, with the addition
of mycophenolate mofetil (MMF) reduces the pool of activated CD4+ T lymphocytes
able to support productive HIV-1 infection, and might have an indirect impact
on the pool of resting, latently infected CD4+ T cells, contributing to its
depletion in vivo. The important question is clearly whether these results will
have an impact on the clinical management of patients with HIV-1 infection,
determining the precise therapeutic function of drugs like CsA and MMF, thus
investigating the effects of these drugs on residual viral replication and the
decay of the latent reservoir, on long-term immunological benefit, and,
ultimately, on clinical benefit. N.
Ref:: 95
----------------------------------------------------
[99]
TÍTULO / TITLE: - Calcineurin and
hypertrophic heart disease: novel insights and remaining questions.
REVISTA
/ JOURNAL: - Cardiovasc Res 2002 Mar;53(4):806-21.
AUTORES
/ AUTHORS: - Bueno OF; van Rooij E; Molkentin JD;
Doevendans PA; De Windt LJ
INSTITUCIÓN
/ INSTITUTION: - Division of Molecular Cardiovascular
Biology, Department of Pediatrics, Children’s Hospital Medical Center,
Cincinnati OH, USA.
RESUMEN
/ SUMMARY: - In the past 2 years, an emerging body of
research has focused on a novel transcriptional pathway involved in the cardiac
hypertrophic response. Ever since its introduction, the significance of the
calcineurin-NFAT module has been subject of controversy. The aim of this review
is to provide both an update on the current status of knowledge and discuss the
remaining issues regarding the involvement of calcineurin in hypertrophic heart
disease. To this end, the molecular biology of calcineurin and its direct
downstream transcriptional effector NFAT are discussed in the context of the
genetic studies that established the existence of this signaling paradigm in
the heart. The pharmacological mode-of-action and specificity of the
calcineurin inhibitors cyclosporine A (CsA) and FK506 is discussed, as well as
their inherent limitations to study the biology of calcineurin. A critical
interpretation is given on studies aimed at analyzing the role of calcineurin
in cardiac hypertrophy using systemic immunosuppression. To eliminate the
controversy surrounding CsA/FK506 usage, recent studies employed genetic
inhibitory strategies for calcineurin, which confirm the pivotal role for this
signal transduction pathway in the ventricular hypertrophy response. Finally,
unresolved issues concerning the role of calcineurin in cardiac pathobiology
are discussed based upon the information available, including its controversial
role in cardiomyocyte viability, the reciprocal relationship between myocyte
Ca(2+) homeostasis and calcineurin activity and the relative importance of calcineurin
in relation to other hypertrophic signaling cascades. N. Ref:: 124
----------------------------------------------------
[100]
TÍTULO / TITLE: - Old and new tools to
dissect calcineurin’s role in pressure-overload cardiac hypertrophy.
REVISTA
/ JOURNAL: - Cardiovasc Res 2002 Feb 1;53(2):294-303.
AUTORES
/ AUTHORS: - Zhang W
INSTITUCIÓN
/ INSTITUTION: - Department of Internal
Medicine/Hypertension Division, The University of Texas Southwestern Medical
Center at Dallas, Dallas, TX 75390-8586, USA. wzhang@mednet.swmed.edu
RESUMEN
/ SUMMARY: - In the last several years, a number of
experiments have implicated a pivotal role of the
calcium/calmodulin-calcineurin dependent pathway as a final common signaling
mechanism by which diverse hypertrophic stimuli converge to mediate
hypertrophic responses in cardiomyocytes. Calcineurin inhibitors, i.e.
cyclosporine A (CsA) and FK506, can interrupt the pathway, thereby preventing
cardiac hypertrophy. The data that convincingly support this novel hypothesis
were derived either from in vitro studies in cultured cardiomyocytes or from in
vivo studies in transgenic mice. However, when the hypothesis was tested in
clinically relevant animal models of cardiac hypertrophy, controversial results
and conclusions emerged. In conventional models of cardiac hypertrophy, two
questions remain to be answered: (1) whether calcineurin is activated in
hypertrophied cardiac muscle, and (2) whether calcineurin inhibitors prevent cardiac
hypertrophy. In addition, clinical observations have revealed that calcineurin
inhibitors appear to exert pro-hypertrophic effects in organ transplant
recipients. The controversies suggest that current calcineurin inhibitors are
blunt tools for testing the hypothesis in pressure-overload hypertrophy in
vivo, because there are so many confounding effects that are associated with
systemic administration of the drugs. As such, new genetic approaches may
overcome some of the problems associated with pharmacological inhibitors. This
invited review will focus on the controversies surrounding the ability of
calcineurin inhibition to prevent conventional (pressure-overload) cardiac
hypertrophy and the new genetic approaches to address the question. N. Ref:: 93
----------------------------------------------------
[101]
TÍTULO / TITLE: - Drug-eluting stents:
potential applications for peripheral arterial occlusive disease.
REVISTA
/ JOURNAL: - J Vasc Interv Radiol 2003
Mar;14(3):291-301.
AUTORES
/ AUTHORS: - Duda SH; Poerner TC; Wiesinger B; Rundback
JH; Tepe G; Wiskirchen J; Haase KK
INSTITUCIÓN
/ INSTITUTION: - Department of Diagnostic Radiology,
University of Tuebingen, Germany. stephan.duda@med.uni-tuebingen.de
RESUMEN
/ SUMMARY: - Many different approaches have been
evaluated to prevent restenosis in stents after vascular implantation.
Currently, drug-eluting stents are extremely promising in suppressing
neointimal hyperplasia. Various animal studies and randomized trials in humans
have shown excellent results in terms of safety and efficacy during
intermediate-term follow-up. This article will give an overview of experimental
and clinical data of the different agents in published and ongoing trials. N. Ref:: 87
----------------------------------------------------
[102]
TÍTULO / TITLE: - Regulation of glycogen
synthesis in human muscle cells.
REVISTA
/ JOURNAL: - Biochem Soc Trans. Acceso gratuito al
texto completo a partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://bst.portlandpress.com/bst//default.htm
●●
Cita: Biochemical Society Transactions: <> 2001 Aug;29(Pt 4):537-41.
AUTORES
/ AUTHORS: - Yeaman SJ; Armstrong JL; Bonavaud SM;
Poinasamy D; Pickersgill L; Halse R
INSTITUCIÓN
/ INSTITUTION: - School of Biochemistry and Genetics,
Medical School, University of Newcastle, Newcastle upon Tyne NE2 4HH, UK. s.j.yeaman@ncl.ac.uk
RESUMEN
/ SUMMARY: - Glucose uptake into muscle and its
subsequent storage as glycogen is a crucial factor in energy homeostasis in
skeletal muscle. This process is stimulated acutely by insulin and is impaired
in both insulin-resistant states and in type 2 diabetes mellitus. A signalling
pathway involving protein kinase B and glycogen synthase kinase 3 seems certain
to have a key role in stimulating glycogen synthesis but other signalling
pathways also contribute, including a rapamycin-sensitive pathway stimulated by
amino acids. Although glycogen synthesis is one of the classical
insulin-regulated pathways, it is also regulated in an insulin-independent
manner; for example glycogen synthesis in muscle is stimulated significantly
after strenuous exercise, with much of this stimulation being independent of
the involvement of insulin. Evidence suggests that glucose and the glycogen
content of the muscle have a key role in this stimulation but the molecular
mechanism has yet to be fully explained.
N. Ref:: 24
----------------------------------------------------
[103]
TÍTULO / TITLE: - The role of T
lymphocytes in the pathogenesis of asthma.
REVISTA
/ JOURNAL: - J Allergy Clin Immunol 2003
Mar;111(3):450-63; quiz 464.
AUTORES
/ AUTHORS: - Larche M; Robinson DS; Kay AB
INSTITUCIÓN
/ INSTITUTION: - Department of Allergy and Clinical
Immunology, Faculty of Medicine, Imperial College London, National Heart and
Lung Institute, London, United Kingdom.
RESUMEN
/ SUMMARY: - There is considerable evidence to support
a role for T cells in asthma, particularly the involvement of T(H)2 cells both
in atopic allergic asthma and in nonatopic and occupational asthma. There might
also be a minor contribution from T©2 CD8+ T cells. Several T(H)2 cytokines
have the potential to modulate airway inflammation, particularly IL-13, which
induces airway hyperresponsiveness independently of IgE and eosinophilia in
animal models. The identification of transcription factors controlling T(H)1
and T(H)2 development further support the T(H)2 hypothesis because GATA3 is
overexpressed and T-bet is underexpressed in the asthmatic airway. Specific T
cell directed immunotherapy might allow induction, modulation, or both of
T-cell responses, and elucidation of the mechanisms of regulatory T cells might
allow further optimization of immunotherapy. Recent advances in our
understanding of dendritic cell function in directing T-cell responses might
uncover further therapeutic targets. The efficacy of cyclosporin A and anti-CD4
treatment in patients with chronic severe asthma argues for continued T-cell
involvement, but whether remodeling contributes to pathology inaccessible to
anti-inflammatory treatment or T-cell immunotherapy will be an important future
question. N. Ref:: 145
----------------------------------------------------
[104]
TÍTULO / TITLE: - Immunophilins in
nervous system degeneration and regeneration.
REVISTA
/ JOURNAL: - Curr Top Med Chem 2003;3(12):1376-82.
AUTORES
/ AUTHORS: - Avramut M; Achim CL
INSTITUCIÓN
/ INSTITUTION: - Department of Pathology, School of
Medicine, University of Pittsburgh, S-433 Biomedical Science Tower, 200 Lothrop
Street, Pittsburgh, PA 15213, USA. avramut@pitt.edu
RESUMEN
/ SUMMARY: - Immunophilins are receptors for
immunosuppressive drugs like cyclosporin A, FK506, rapamycin and their non-
immunosuppressive analogs, which are collectively referred to as “immunophilin
ligands” (IPL). Cyclosporin A binds to a class of IP called cyclophilins,
whereas the receptors for FK506 and rapamycin belong to the family of FK506-
binding proteins (FKBP). The latter are designated according to their molecular
weight: FKBP12, 25, 52 etc. FKBP levels in the rat brain are up to 50 times
higher than in the immune system. FKBP12 is associated with IP3 and ryanodine
receptors present on the endoplasmic reticulum and plays a role in stabilizing
calcium release. It has also been proposed to be a modulator of the TGFbeta
receptor activity. Crush injury of facial or sciatic nerves in rat leads to
markedly increased FKBP12 levels in the respective nerve nuclei and this
increase is related to nerve regeneration. Cyclophilin A protects cells from
death following expression of mutant Cu/ Zn superoxide dismutase, which is
associated with familial amyotrophic lateral sclerosis. Our recent studies show
that FKBP12 and FKBP52 are expressed in the human nervous system, especially in
the substantia nigra- deep gray matter axis. In neurodegenerative diseases,
FKBP12 levels increase in neurons situated in areas of pathology. This IP
colocalizes with synaptophysin and alpha- synuclein, suggesting that it may
become a novel marker of pathology. Immunophilins participate in axonal
transport, synaptic vesicle assembly and may play a role in neuroprotection
against abnormal protein aggregation, suggesting a potential avenue of
therapeutic interventions. N.
Ref:: 62
----------------------------------------------------
[105]
TÍTULO / TITLE: - Rapamycin in
combination with cyclosporine or tacrolimus in liver, pancreas, and kidney
transplantation.
REVISTA
/ JOURNAL: - Transplant Proc 2003 May;35(3
Suppl):201S-208S.
AUTORES
/ AUTHORS: - MacDonald AS
INSTITUCIÓN
/ INSTITUTION: - Department of Surgery, Dalhousie
University, Halifax, Nova Scotia, Canada. Allan.macdonald@dal.ca
RESUMEN
/ SUMMARY: - A 10-year experience with the
immunosuppressive drug rapamycin that begins in the laboratory then extends
through multicentre trials in combination with cyclosporine in kidney
transplant recipients, exploration of its use as a single agent and in
combination with tacrolimus, and its potential in nonrenal organs is described.
Rapamycin is a potent inhibitor of endothelial injury in rat aortic allografts.
When added to full-dose cyclosporine it achieves low rejection rates, but it
augments the nephrotoxicity and hyperlipidemia of cyclosporine. On the other
hand, it allows discontinuation of calcineurin inhibitors in stable kidney and
liver patients suffering from nephrotoxicity late posttransplant. At least in
Caucasian patients, discontinuation of cyclosporine is possible as early as 3
months post-kidney transplant. In combination with low-dose tacrolimus,
exceptionally low rates of rejection were seen in recipients of kidney,
pancreas, and liver recipients with preservation of excellent renal function.
These pilot studies have been confirmed in several single-centre and, more
recently, multicentre trials in kidney and pancreas transplantation. The
side-effect profile of hyperlipidemia, lymphocoeles, delayed wound healing, and
possible liver effects are coming into focus, and ways of minimizing these
problems being introduced. The lessons learned include the need for early
adequate blood levels, the lack of correlation between dose and drug exposure,
and the potency that allows marked dose reductions in calcineurin inhibitors
and steroids. N.
Ref:: 36
----------------------------------------------------
[106]
TÍTULO / TITLE: - Treatment of atopic
dermatitis and impact on quality of life: a review with emphasis on topical
non-corticosteroids.
REVISTA
/ JOURNAL: - Pharmacoeconomics 2003;21(3):159-79.
AUTORES
/ AUTHORS: - Schiffner R; Schiffner-Rohe J; Landthaler
M; Stolz W
INSTITUCIÓN
/ INSTITUTION: - Department of Dermatology, University of
Regensburg, Regensburg, Germany. jr.schiffner@t-online.de
RESUMEN
/ SUMMARY: - Atopic dermatitis (AD) is a chronic skin
disease with increasing prevalence and rising costs. Stigmatisation and
pruritus are only some aspects of potential quality-of-life (QOL) impairments.
AD is not curable and repeated treatments are often necessary. At present,
treatment with topically-applied corticosteroids is state-of-the-art for mild
to moderate flare-ups. However, many patients are worried about the use of
corticosteroids due to the widespread fear of adverse effects. In this review
the present literature is analysed concerning impact on quality of life for
topically-applicable alternatives to the state-of-the-art treatment. For
comparison reasons, data from other treatment modalities are additionally
given. Characteristics of studies were analysed using ‘general’ (year and mode
of publication, type and aim of study, number of patients, and clinical
measurement) and ‘QOL specific’ criteria (type and number of QOL measurements
including relevance for study aim and age group, validation in used language,
sensitivity to change, and improvement at end of study). QOL data are published
only in the minority of studies evaluating treatment efficacy and do not cover
the variety of possible therapies. Data are available for tacrolimus,
pimecrolimus, UVA/UVB combination and UVB narrowband (topical
non-corticosteroidal treatments), as well as for topical corticosteroids,
cyclosporin, and inpatient treatment. All studies provided a marked improvement
in quality of life after therapy. One study assessed quality of life after a
treatment-free follow-up period obtaining a clear increase in impact on quality
of life. Since studies used different QOL measurements and vary in inclusion
criteria, treatment schedules and presentation of results, a comparison of QOL
improvement is not recommended. A single randomised study compared topically
applied non-corticosteroidal treatment (UVA/UVB combination) with another
treatment modality (cyclosporin) and found no difference in QOL improvement. At
present, there is a clear lack of controlled randomised studies evaluating
different active treatment modalities and their impact on quality of life.
Consensus meetings are desirable to formulate guidelines for the selection and
correct use of QOL measurements. Patients’ fear of side effects (e.g.
concerning corticosteroids) should be integrated in QOL questionnaires for
evaluation of possible compliance problems and real costs. Since relapse after
treatment is frequent in AD, QOL measurements should also be performed after a
treatment-free follow-up period. At present, we can not answer the question
‘which treatment best improves quality of life in AD?’. N. Ref:: 128
----------------------------------------------------
[107]
TÍTULO / TITLE: - St John’s Wort
supplements endanger the success of organ transplantation.
REVISTA
/ JOURNAL: - Arch Surg 2002 Mar;137(3):316-9.
AUTORES
/ AUTHORS: - Ernst E
INSTITUCIÓN
/ INSTITUTION: - Department of Complementary Medicine,
School of Sport and Health Sciences, University of Exeter, 25 Victoria Park Rd,
Exeter EX2 4NT, England. E.Ernst@ex.ac.uk
RESUMEN
/ SUMMARY: - HYPOTHESIS: St John’s wort is one of the
most popular herbal medicines, and health care professionals often are unaware
that their patients take such supplements. St John’s wort causes a decrease in
cyclosporine levels, thus endangering the success of organ transplantations.
DESIGN: Systematic review. METHODS: Five independent computerized literature
searches were conducted to identify all reports of such interactions. Data were
extracted and are summarized in narrative form. RESULTS: Eleven case reports
and 2 case series were located. In most instances, causality between St John’s
wort and the clinical or biochemical result is well established. The mechanism
of interaction between St John’s wort and cyclosporine has been recently
elucidated and involves both P-glycoprotein and cytochrome P 450 3A4
expression. Collectively these data leave little doubt that St John’s wort
interacts with cyclosporine, causing a decrease of cyclosporine blood levels
and leading in several cases to transplant rejection. CONCLUSIONS: St John’s
wort can endanger the success of organ transplantations. Adequate information
may be the best way to avoid future incidences. N. Ref:: 33
----------------------------------------------------
[108]
TÍTULO / TITLE: - Sirolimus and
mycophenolate mofetil for calcineurin-free immunosuppression in renal
transplant recipients.
REVISTA
/ JOURNAL: - Am J Kidney Dis 2001 Oct;38(4 Suppl
2):S16-21.
AUTORES
/ AUTHORS: - Pescovitz MD; Govani M
INSTITUCIÓN
/ INSTITUTION: - Departments of Surgery,
Microbiology/Immunology, and Medicine, Indiana University, Indianapolis, IN
46202, USA. mpescov@iupui.edu
RESUMEN
/ SUMMARY: - Calcineurin inhibitors, such as
cyclosporine and tacrolimus, have been available for almost 20 years. Although
these drugs are highly effective and represent the mainstay of transplant
immunosuppression, they are associated with acute and chronic nephrotoxicity.
Acute nephrotoxicity, which occurs in the early period after transplantation,
leads to a higher rate of dialysis, and chronic nephrotoxicity may eventually
result in graft loss. Acute and chronic nephrotoxicity is becoming more common
as the use of marginal kidneys for transplantation increases. Two recently
available immunosuppressive agents, mycophenolate mofetil and sirolimus
(rapamycin), have no nephrotoxicity. The use of these drugs in combination with
other agents has led to the development of new paradigms of immunosuppressive
therapy. This paper reviews the results of clinical trials that have
investigated these new approaches to immunosuppression in renal transplant
recipients. N. Ref:: 9
----------------------------------------------------
[109]
TÍTULO / TITLE: - Engineered CD3
antibodies for immunosuppression.
REVISTA
/ JOURNAL: - Clin Exp Immunol 2003 Sep;133(3):307-9.
AUTORES
/ AUTHORS: - Renders L; Valerius T N. Ref:: 30
----------------------------------------------------
[110]
TÍTULO / TITLE: - St John’s wort
(Hypericum perforatum): drug interactions and clinical outcomes.
REVISTA
/ JOURNAL: - Br J Clin Pharmacol 2002 Oct;54(4):349-56.
AUTORES
/ AUTHORS: - Henderson L; Yue QY; Bergquist C; Gerden
B; Arlett P
INSTITUCIÓN
/ INSTITUTION: - Pharmacovigilance Group, Medicines Control
Agency, UK. leigh.henderson@mca.gsi.gov.uk
RESUMEN
/ SUMMARY: - AIMS: The aim of this work is to identify
the medicines which interact with the herbal remedy St John’s wort (SJW), and
the mechanisms responsible. METHODS: A systematic review of all the available
evidence, including worldwide published literature and spontaneous case reports
provided by healthcare professionals and regulatory authorities within Europe
has been undertaken. RESULTS: A number of clinically significant interactions
have been identified with prescribed medicines including warfarin,
phenprocoumon, cyclosporin, HIV protease inhibitors, theophylline, digoxin and
oral contraceptives resulting in a decrease in concentration or effect of the
medicines. These interactions are probably due to the induction of cytochrome
P450 isoenzymes CYP3A4, CYP2C9, CYP1A2 and the transport protein P-glycoprotein
by constituent(s) in SJW. The degree of induction is unpredictable due to
factors such as the variable quality and quantity of constituent(s) in SJW
preparations. In addition, possible pharmacodynamic interactions with selective
serotonin re-uptake inhibitors and serotonin (5-HT(1d)) receptor-agonists such
as triptans used to treat migraine were identified. These interactions are
associated with an increased risk of adverse reactions. CONCLUSIONS: In Sweden
and the UK the potential risks to patients were judged to be significant and
therefore information about the interactions was provided to health care
professionals and patients. The product information of the licensed medicines
involved has been amended to reflect these newly identified interactions and
SJW preparations have been voluntarily labelled with appropriate warnings. N. Ref:: 44
----------------------------------------------------
[111]
TÍTULO / TITLE: - Treatment of
gammaherpesvirus-related neoplastic disorders in the immunosuppressed host.
REVISTA
/ JOURNAL: - Semin Hematol 2003 Apr;40(2):163-71.
●●
Enlace al texto completo (gratuito o de pago) 1053/shem.2003.50016
AUTORES
/ AUTHORS: - Little RF; Yarchoan R
INSTITUCIÓN
/ INSTITUTION: - HIV and AIDS Malignancy Branch, Center for
Cancer Research, National Cancer Institute, National Institutes of Health,
Bethesda, MD 20892, USA.
RESUMEN
/ SUMMARY: - Neoplastic disease is a frequent
complication in patients with acquired immunodeficiency disease (AIDS) and
other immunodeficiencies. Many such neoplasms are caused by either Epstein-Barr
virus (EBV) or Kaposi’s sarcoma-associated herpes virus (KSHV). The treatment
of such patients can be challenging. At the same time, the viral origin of
these tumors offers targets to develop pathogenesis-based therapies. Standard
therapies for these diseases involve such approaches as treating the underlying
immunodeficiency, cytotoxic chemotherapy, and immunologic antitumor therapy.
Novel therapy approaches include specific immune therapy and anti-angiogenesis approaches,
now under development. N.
Ref:: 105
----------------------------------------------------
[112]
TÍTULO / TITLE: - Calcineurin phosphatase
in signal transduction: lessons from fission yeast.
REVISTA
/ JOURNAL: - Genes Cells 2002 Jul;7(7):619-27.
AUTORES
/ AUTHORS: - Sugiura R; Sio SO; Shuntoh H; Kuno T
INSTITUCIÓN
/ INSTITUTION: - Division of Molecular Pharmacology and
Pharmacogenomics, Department of Genome Sciences, Kobe University Graduate
School of Medicine, Kobe 650-0017, Japan.
RESUMEN
/ SUMMARY: - Calcineurin (protein phosphatase 2B), the
only serine/threonine phosphatase under the control of Ca2+/calmodulin, is an
important mediator in signal transmission, connecting the Ca2+-dependent
signalling to a wide variety of cellular responses. Furthermore, calcineurin is
specifically inhibited by the immunosuppressant drugs cyclosporin A and
tacrolimus (FK506), and these drugs have been a powerful tool for identifying
many of the roles of calcineurin. Calcineurin is enriched in the neural tissues,
and also distributes broadly in other tissues. The structure of the protein is
highly conserved from yeast to man. The combined use of powerful genetics and
of specific calcineurin inhibitors in fission yeast Schizosaccharomyces pombe
(S. pombe) identified new components of the calcineurin pathway, and defined
new roles of calcineurin in the regulation of the many cellular processes.
Recent data has revealed functional interactions in which calcineurin
phosphatase is involved, such as the cross-talk between the Pmk1 MAP kinase
signalling, or the PI signalling. Calcineurin also participates in membrane
traffic and cytokinesis of fission yeast through its functional connection with
members of the small GTPase Rab/Ypt family, and Type II myosin, respectively.
These findings highlight the potential of fission yeast genetic studies to
elucidate conserved elements of signal transduction cascades. N. Ref:: 51
----------------------------------------------------
[113]
TÍTULO / TITLE: - Minimizing calcineurin
inhibitor drugs in renal transplantation.
REVISTA
/ JOURNAL: - Transplant Proc 2003 May;35(3
Suppl):118S-121S.
AUTORES
/ AUTHORS: - Flechner SM
INSTITUCIÓN
/ INSTITUTION: - Section of Renal Transplantation,
Transplant Center A110, Cleveland Clinic Foundation, Cleveland, Ohio 44195,
USA.
RESUMEN
/ SUMMARY: - Calcineurin inhibitor drugs (CNI),
primarily cyclosporine then tacrolimus, have been the centerpieces of
maintenance immunosuppression for kidney transplantation since their
introduction in the 1980s. While these drugs have been responsible for improved
short-term outcomes and diminished rates of acute rejection, they are
nephrotoxic and can cause permanent renal injury in many patients. Indeed, some
have found that at 10 years after transplantation, the benefits of CNI drugs
have been lost compared to the previous generation of maintenance
immunosuppression. The use of these agents over many years contributes to the
antigen-independent decline in renal function referred to as chronic allograft
nephropathy. However, it remains unclear to what degree the use of CNI drugs
contribute to ultimate graft loss. For these reasons immunosuppressive
alternatives to CNI drugs have begun to emerge during the past few years. The
recent introduction of the potent immunosuppressive agent sirolimus has
afforded an opportunity to develop a regimen designed to maximize prophylaxis
of early acute rejection, absent drug-induced nephrotoxicity. It was our
feeling that the combination of antibody induction therapy combined with
sirolimus substitution in a three-drug maintenance regimen, would provide the
best posttransplant renal function and lowest rates of acute rejection. We have
developed a CNI-free immunosuppressive regimen consisting of basiliximab
induction, followed by sirolimus, MMF and steroids. Using this protocol we
demonstrated comparable transplant outcomes with improved renal function in
adult recipients of primary renal transplants. Limiting nephrotoxic
immunosuppression should be considered an important goal; but requires
sufficient long-term follow-up to support the benefits suggested from initial
analysis of the data. N.
Ref:: 23
----------------------------------------------------
[114]
TÍTULO / TITLE: - FTY720: targeting
G-protein-coupled receptors for sphingosine 1-phosphate in transplantation and
autoimmunity.
REVISTA
/ JOURNAL: - Curr Opin Immunol 2002 Oct;14(5):569-75.
AUTORES
/ AUTHORS: - Brinkmann V; Lynch KR
INSTITUCIÓN
/ INSTITUTION: - Novartis Pharma AG Transplantation
Research WSJ-386.101, CH-4002 Basel, Switzerland. volker.brinkmann@pharma.novartis.com
RESUMEN
/ SUMMARY: - The novel immunomodulator FTY720 is
remarkably effective in models of transplantation and autoimmunity. Recent data
show that phosphorylated FTY720 is an agonist at four sphingosine 1-phosphate
receptors. Stimulation of sphingosine 1-phosphate receptors leads to
sequestration of lymphocytes in secondary lymphatic tissues and thus away from
inflammatory lesions and graft sites. N.
Ref:: 44
----------------------------------------------------
[115]
TÍTULO / TITLE: - Histopathological study
of intrahepatic islets transplanted in the nonhuman primate model using
edmonton protocol immunosuppression.
REVISTA
/ JOURNAL: - J Clin Endocrinol Metab. Acceso gratuito
al texto completo a partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://jcem.endojournals.org/
●●
Cita: J. of Clin Endocrinol & Metab: <> 2002 Dec;87(12):5424-9.
AUTORES
/ AUTHORS: - Hirshberg B; Mog S; Patterson N; Leconte
J; Harlan DM
INSTITUCIÓN
/ INSTITUTION: - Transplantation and Autoimmunity Branch,
National Institute of Diabetes and Digestive and Kidney Diseases, National
Institutes of Health, Bethesda, Maryland 20892, USA.
RESUMEN
/ SUMMARY: - While islet cell transplantation is a
promising way to restore insulin independence to patients with type I diabetes
mellitus, a detailed histological analysis of the transplanted, intraportal
islets has not yet been reported. Rhesus macaques underwent total
pancreatectomy, then had allogeneic isolated islets infused into their portal
vein, followed by daclizumab, tacrolimus, and sirolimus to prevent islet
rejection. Islets were evenly distributed among the liver lobes. Liver sections
from a primate given allogeneic islets 5 d earlier did not display any islet
capillary formation, whereas intrahepatic islets transplanted 30 and 90 d
before euthanasia showed an abundant capillary supply. Localized hepatocellular
glycogenosis was observed surrounding the islets in a primate with functioning
islets 7 months post transplant. Liver sections from a primate that rejected
islets transplanted 2 months prior displayed only islet remnants with prominent
local lymphohistiocytic inflammation and an occasional capillary. We conclude
that islets develop an abundant vascular supply within 30 d following
transplant and because capillaries persist even following rejection, that the
vascular cells are likely from the recipient. While transplanted islets were
not vascularized early post transplant, the primates remained insulin
independent. The long-term consequence of islets in the liver, marked by the
glycogenosis, remains unknown and warrants further study.
----------------------------------------------------
[116]
TÍTULO / TITLE: - The mucosa of the small
intestine: how clinically relevant as an organ of drug metabolism?
REVISTA
/ JOURNAL: - Clin Pharmacokinet 2002;41(4):235-53.
AUTORES
/ AUTHORS: - Doherty MM; Charman WN
INSTITUCIÓN
/ INSTITUTION: - Department of Pharmaceutics, Victorian
College of Pharmacy, Monash University, 381 Royal Parade, Parkville, Victoria
3052, Australia. margaret.doherty@vcp.monash.edu.au
RESUMEN
/ SUMMARY: - The intestinal mucosa is capable of
metabolising drugs via phase I and II reactions. Increasingly, as a result of
in vitro and in vivo (animal and human) data, the intestinal mucosa is being
implicated as a major metabolic organ for some drugs. This has been supported
by clinical studies of orally administered drugs (well-known examples include
cyclosporin, midazolam, nifedipine and tacrolimus) where intestinal drug
metabolism has significantly reduced oral bioavailability. This review
discusses the intestinal properties and processes that contribute to drug
metabolism. An understanding of the interplay between the processes controlling
absorption, metabolism and P-glycoprotein-mediated efflux from the intestinal
mucosa into the intestinal lumen facilitates determination of the extent of the
intestinal contribution to first-pass metabolism. The clinical relevance of
intestinal metabolism, however, depends on the relative importance of the
metabolic pathway involved, the therapeutic index of the drug and the inherent
inter- and intra-individual variability. This variability can stem from genetic
(metabolising enzyme polymorphisms) and/or non-genetic (including concomitant
drug and food intake, route of administration) sources. An overwhelming
proportion of clinically relevant drug interactions where the intestine has
been implicated as a major contributor to first-pass metabolism involve drugs
that undergo cytochrome P450 (CYP) 3A4-mediated biotransformation and are
substrates for the efflux transporter P-glycoprotein. Much work is yet to be
done in characterising the clinical impact of other enzyme systems on drug
therapy. In order to achieve this, the first-pass contributions of the
intestine and liver must be successfully decoupled. N. Ref:: 130
----------------------------------------------------
[117]
TÍTULO / TITLE: - Transplantation:
toxicokinetics and mechanisms of toxicity of cyclosporine and macrolides.
REVISTA
/ JOURNAL: - Curr Opin Investig Drugs 2003
Nov;4(11):1287-96.
AUTORES
/ AUTHORS: - Serkova N; Christians U
INSTITUCIÓN
/ INSTITUTION: - Department of Anesthesiology, Clinical
Research & Development, University of Colorado Health Sciences Center, 4200
East Ninth Ave, Room UH-2122, Campus Box B113, Denver, CO 80262, USA.
RESUMEN
/ SUMMARY: - For over two decades, calcineurin
inhibitors (CIs) have been the mainstay of immunosuppressive therapy following
solid-organ transplantation. However, CI nephrotoxicity is one of the main
contributors to chronic kidney allograft dysfunction. A novel class of
immunosuppressants that inhibit the kinase mammalian target of rapamycin
(mTOR), although not nephrotoxic themselves, enhance CI nephrotoxicity. The
biochemical basis of CI toxicity and their toxicodynamic interaction with mTOR
inhibitors is still poorly understood. Studies using a magnetic resonance
spectroscopy-based metabonomic approach indicate that CI toxicity is caused by
drug-induced mitochondrial dysfunction and that mTOR inhibitors enhance the negative
effects of CIs on cell energy metabolism.
N. Ref:: 77
----------------------------------------------------
[118]
TÍTULO / TITLE: - Risk factors for and
management of post-transplantation cardiovascular disease.
REVISTA
/ JOURNAL: - BioDrugs 2001;15(4):261-78.
AUTORES
/ AUTHORS: - Fellstrom B
INSTITUCIÓN
/ INSTITUTION: - Department of Medical Sciences, University
Hospital, SE-751 85 Uppsala, Sweden. bengt.fellstrom@medsci.uu.se
RESUMEN
/ SUMMARY: - The mortality rates due to cardiovascular
disease (CVD) in transplant recipients are greater than in the general
population. CVD is a major cause of both graft loss and patient death in renal
transplant recipients, and improving cardiovascular health in transplant
recipients will presumably help to extend both patient and graft survival.
Further studies are needed to better evaluate the effectiveness of risk
modification on subsequent CVD morbidity and mortality. There is no reason to
consider risk factors for CVD such as hyperlipidaemia, hypertension and
diabetes mellitus in transplant recipients differently from in the general
population. In addition, there are specific transplantation risk factors such
as acute rejection episodes and the use of immunosuppressive drugs. It is
obvious that several of the immunosuppressive agents used today have
disadvantageous influences on risk factors for CVD such as hyperlipidaemia,
hypertension and post-transplantation diabetes mellitus (PTDM), but the
relative importance of immunosuppressant-induced increases in these risk
factors is basically unknown. This may be a strong argument for the selective
use and individual tailoring of immunosuppressive agents based upon the risk
factor profile of the patient, without jeopardising the function of the graft.
Hyperlipidaemia is common after transplantation, and immunosuppression with
corticosteroids, cyclosporin, or sirolimus (rapamycin) causes different types
of post-transplantation hyperlipidaemia. However, to date, no studies have
demonstrated that lipid lowering strategies significantly reduce CVD morbidity
or mortality and improve allograft survival in transplant recipients. Several
studies using preventive or interventional approaches are ongoing and will be
reported in the near future. Post-transplantation hypertension appears to be a
major risk factor determining graft and patient survival, and immunosuppressive
agents have different effects on hypertension. Controlled studies support the
opinion that post-transplantation hypertension must be treated as strictly as
in a population with essential hypertension, diabetes mellitus, or chronic
renal failure. As increasing numbers of immunosuppressive agents become
available for use, we may be in a better position to tailor immunosuppressive
therapy to the individual patient, avoiding the use of diabetogenic drugs, drug
combinations, or inappropriate doses in patients susceptible to PTDM. Multiple
acute rejection episodes have also been demonstrated to be a risk factor for
CVD - a strong argument for the use of immunosuppressive drugs to reduce acute
rejection. Until we have a better understanding from ongoing landmark studies
on the management of CVD, presently available therapy to reduce risk factors
needs to be used together with individual tailoring of immunosuppressive
therapy with the aim of reducing CVD in these patients. N. Ref:: 138
----------------------------------------------------
[119]
TÍTULO / TITLE: - The effect of
immunosuppressive protocols on spontaneous CNS remyelination following
toxin-induced demyelination.
REVISTA
/ JOURNAL: - J Neuroimmunol 2001 Oct 1;119(2):261-8.
AUTORES
/ AUTHORS: - Smith PM; Franklin RJ
INSTITUCIÓN
/ INSTITUTION: - Department of Clinical Veterinary
Medicine, University of Cambridge, Madingley Road, CB3 0ES, Cambridge, UK.
RESUMEN
/ SUMMARY: - Glial cell transplantation is a potential
therapy for human demyelinating disease, though obtaining large numbers of
human myelinating cells for transplantation remains a major stumbling block.
Autologous transplantation is currently not possible, since the adult human CNS
is not a good source of oligodendrocyte precursors, and long-term
immunosuppression of engrafted allogeneic or xenogeneic cells is therefore
likely to be necessary. Immunosuppressive drugs may need to be used in
situations where more recent, active areas of demyelination are undergoing
endogenous remyelination. It is therefore pertinent to establish the extent to
which immunosuppressive protocols will suppress spontaneous remyelination. In
order to investigate this issue, we created demyelinating lesions in the spinal
cord of adult rats and compared the extent of remyelination in animals
receiving different immunosuppressive treatments. In animals given only
cyclosporin A, there was no difference in the extent of either Schwann cell or
oligodendrocyte remyelination of ethidium bromide-induced demyelinating
lesions. However, in animals given cyclophosphamide, either alone or in
combination with cyclosporin, there was a significant reduction in the extent
of oligodendrocyte-mediated remyelination. These results demonstrate that
cyclophosphamide is deleterious to oligodendrocyte remyelination and for this
reason should be used with caution in patients with demyelinating disease.
----------------------------------------------------
[120]
TÍTULO / TITLE: - Non-steroidal topical
immunomodulators provide skin-selective, self-limiting treatment in atopic
dermatitis.
REVISTA
/ JOURNAL: - Eur J Dermatol 2003 Sep-Oct;13(5):455-61.
AUTORES
/ AUTHORS: - Bos JD
INSTITUCIÓN
/ INSTITUTION: - Department of Dermatology A0-235, Academic
Medical Centre, University of Amsterdam, PO Box 22700, 1100 DE Amsterdam, The
Netherlands. j.d.bos@amc.uva.nl
RESUMEN
/ SUMMARY: - Topical corticosteroids are the mainstay
of treatment for atopic dermatitis; however, their clinical utility is limited
by potential side effects. Recently, the steroid-free topical immunomodulators
tacrolimus ointment and pimecrolimus cream have become available. These agents
provide effective treatment without causing skin atrophy or other steroidal
side effects, and their physiochemical properties, such as relatively large
molecular size and high lipophilicity, limit diffusion through skin and into
the bloodstream, providing skin-selective treatment. Clinical trials with more
than 1,700 paediatric and adult patients have demonstrated that treatment with
either agent is associated with minimal systemic absorption of tacrolimus or
pimecrolimus. Additionally, studies have shown that percutaneous absorption of
tacrolimus decreases as treatment continues and clinical improvement occurs.
This self-limiting facet of the treatment, together with the skin-selectivity
of topical immunomodulators, is reflected in the good safety and tolerability
profiles of these agents, which promise to significantly improve the long-term
management of atopic dermatitis. N.
Ref:: 56
----------------------------------------------------
[121]
TÍTULO / TITLE: - The role of
phosphatases in TOR signaling in yeast.
REVISTA
/ JOURNAL: - Curr Top Microbiol Immunol 2004;279:19-38.
AUTORES
/ AUTHORS: - Duvel K; Broach JR
INSTITUCIÓN
/ INSTITUTION: - Department of Molecular Biology, Princeton
University, Princeton, NJ 08544, USA.
RESUMEN
/ SUMMARY: - The TOR pathway controls cellular
functions necessary for cell growth and proliferation of yeast and larger
eukaryotes. The search for members of the TOR signaling cascade in yeast led to
the discovery of type 2A protein phosphatases (PP2A) as important players
within the pathway. We describe the roles in yeast of PP2A and the closely
related phosphatase, Sit4, and then focus on complexes formed between the
catalytic subunit of these phosphatases and Tap42, a direct target of the Tor
protein kinases in yeast. Recent results suggest that Tap42 mediates many of
the Tor functions in yeast, especially those involved in transcriptional
modulation. However, whether Tap42 executes its function by inhibiting
phosphatase activity or by activating phosphatases is still uncertain. In
addition, Tor affects some transcriptional and physiological processes through
Tap42 independent pathways. Thus, Tor proteins use multiple mechanisms to
regulate transcriptional and physiological processes in yeast. N. Ref:: 46
----------------------------------------------------
[122]
TÍTULO / TITLE: - Raptor and mTOR:
subunits of a nutrient-sensitive complex.
REVISTA
/ JOURNAL: - Curr Top Microbiol Immunol
2004;279:259-70.
AUTORES
/ AUTHORS: - Kim DH; Sabatini DM
INSTITUCIÓN
/ INSTITUTION: - Whitehead Institute for Biomedical
Research, Nine Cambridge Center, Cambridge, MA 02142, USA.
RESUMEN
/ SUMMARY: - mTOR/RAFT1/FRAP is the target of the
FKBP12-rapamycin complex as well as a central component of a nutrient- and
hormone-sensitive pathway that controls cellular growth. Recent work reveals
that mTOR interacts with a novel evolutionarily conserved protein that we named
raptor, for “regulatory associated protein of mTOR.” Raptor has several roles
in the mTOR pathway. It is necessary for nutrient-mediated activation of the
downstream effector S6K1 and increases in cell size. In addition, under
conditions that repress the mTOR pathway, the association of raptor with mTOR
is strengthened, leading to a decrease in mTOR kinase activity. Raptor is a
critical component of the mTOR pathway that regulates cell growth in response
to nutrient levels by associating with mTOR.
N. Ref:: 40
----------------------------------------------------
[123]
TÍTULO / TITLE: - Therapeutic drug
monitoring of immunosuppressant drugs in clinical practice.
REVISTA
/ JOURNAL: - Clin Ther 2002 Mar;24(3):330-50;
discussion 329.
AUTORES
/ AUTHORS: - Kahan BD; Keown P; Levy GA; Johnston A
INSTITUCIÓN
/ INSTITUTION: - Division of Immunology and Organ
Transplantation, University of Texas Health Science Center at Houston Medical
School, 77030, USA. Barry.D.Kahan@uth.tmc.edu
RESUMEN
/ SUMMARY: - BACKGROUND: Therapeutic drug monitoring
(TDM) is essential to maintain the efficacy of many immunosuppressant drugs
while minimizing their toxicity. TDM has become more refined with the
development of new monitoring techniques and more specific assays. OBJECTIVE:
This article summarizes current data on TDM of the following immunosuppressant
drugs used in organ transplantation: cyclosporine, tacrolimus, sirolimus,
everolimus, and mycophenolate mofetil. METHODS: Published data were identified
by a MEDLINE search of the English-language literature through March 2001 using
the terms therapeutic drug monitoring, cyclosporine, tacrolimus, sirolimus,
everolimus, and mycophenolate mofetil. Relevant conference abstracts were also
included. RESULTS: TDM of cyclosporine has been well studied, and recent
findings indicate that monitoring of drug levels 2 hours after dosing is a more
sensitive predictor of outcome than trough (C0) monitoring. C0 levels are being
used more widely in TDM of tacrolimus; however, the relationship between C0 and
area under the curve has varied widely in clinical trials, with correlations
ranging from 0.11 to 0.92. The use of TDM of sirolimus, everolimus, and
mycophenolate mofetil is evolving rapidly. CONCLUSIONS: TDM of
immunosuppressant drugs that have a narrow therapeutic index is an increasingly
useful tool for minimizing drug toxicity while maximizing prevention of graft
loss and organ rejection. N.
Ref:: 85
----------------------------------------------------
[124]
TÍTULO / TITLE: - A prospective study of
rapid corticosteroid elimination in simultaneous pancreas-kidney
transplantation: comparison of two maintenance immunosuppression protocols:
tacrolimus/mycophenolate mofetil versus tacrolimus/sirolimus.
REVISTA
/ JOURNAL: - Transplantation 2002 Jan 27;73(2):169-77.
AUTORES
/ AUTHORS: - Kaufman DB; Leventhal JR; Koffron AJ;
Gallon LG; Parker MA; Fryer JP; Abecassis MM; Stuart FP
INSTITUCIÓN
/ INSTITUTION: - Department of Surgery, Division of
Transplantation, Northwestern University Medical School, 675 N. St. Clair
Street, Galter Pavilion, Suite 17-200, Chicago, IL 60611, USA.
RESUMEN
/ SUMMARY: - BACKGROUND: We examined the feasibility of
rapid corticosteroid elimination in simultaneous pancreas kidney
transplantation. METHODS: Forty consecutive simultaneous pancreas-kidney (SPK) transplant
recipients were enrolled in a prospective study in which antithymocyte globulin
induction and 6 days of corticosteroids were administered along with tacrolimus
and MMF (n=20) or tacrolimus and sirolimus (n=20). Mean+/-SD follow-up for
recipients receiving tacrolimus/MMF and tacrolimus/sirolimus were 12.7+/-3.9
and 13.4+/-2.9 months, respectively. Patient and graft survival, and rejection
rates were compared to an historical control group (n=86; mean follow-up
41.5+/-15.4 months) of SPK recipients that received induction and tacrolimus,
MMF, and corticosteroids. RESULTS: Demographic characteristics of recipient and
donor variables were similar among all groups. The 1-year actuarial patient,
kidney, and pancreas survival rates in the 40 SPK transplant recipients with
rapid corticosteroid elimination were 100, 100, and 100%, respectively. In the
historical control group the 1-year actual patient, kidney, and pancreas
survival rates were 96.5, 93.0, and 91.9%, respectively. The 1-year
rejection-free survival rate recipients in the rapid steroid elimination group
collectively was 97.5 vs 80.2% in the historical control group (P=0.034). At 6
and 12 months posttransplant the serum creatinine values remained stable in all
groups. CONCLUSIONS: We conclude that chronic corticosteroid exposure is not
required in SPK transplant recipients receiving antithymocyte globulin
induction and maintenance immuno-suppression consisting of either tacrolimus
and mycophenolate mofetil or tacrolimus and sirolimus.
----------------------------------------------------
[125]
TÍTULO / TITLE: - The potential of
chitosan in ocular drug delivery.
REVISTA
/ JOURNAL: - J Pharm Pharmacol 2003 Nov;55(11):1451-63.
●●
Enlace al texto completo (gratuito o de pago) 1211/0022357022476
AUTORES
/ AUTHORS: - Alonso MJ; Sanchez A
INSTITUCIÓN
/ INSTITUTION: - Department of Pharmacy and Pharmaceutical
Technology, Faculty of Pharmacy, University of Santiago de Compostela, 15782
Santiago de Compostela, España. ffmjalon@usc.es
RESUMEN
/ SUMMARY: - This paper presents an overview of the
potential of chitosan-based systems for improving the retention and
biodistribution of drugs applied topically onto the eye. Besides its low
toxicity and good ocular tolerance, chitosan exhibits favourable biological
behaviour, such as bioadhesion- and permeability-enhancing properties, and also
interesting physico-chemical characteristics, which make it a unique material
for the design of ocular drug delivery vehicles. The review summarizes the
techniques for the production of chitosan gels, chitosan-coated colloidal
systems and chitosan nanoparticles, and describes their mechanism of action
upon contact with the ocular mucosa. The results reported until now have
provided evidence of the potential of chitosan gels for enhancing and
prolonging the retention of drugs on the eye surface. On the other hand,
chitosan-based colloidal systems were found to work as transmucosal drug
carriers, either facilitating the transport of drugs to the inner eye
(chitosan-coated colloidal systems containing indometacin) or their
accumulation into the corneal/conjunctival epithelia (chitosan nanoparticles
containing ciclosporin). Finally, the tolerance, toxicity and biodegradation of
the carriers under evaluation were reviewed.
N. Ref:: 75
----------------------------------------------------
[126]
TÍTULO / TITLE: - Rejection rate in
living donor kidney transplantation with and without basiliximab in
tacrolimus/mycophenolate mofetil-based protocol.
REVISTA
/ JOURNAL: - Transplant Proc 2003 Mar;35(2):653-4.
AUTORES
/ AUTHORS: - Rahamimov R; Yussim A; After T; Lustig S;
Bar-Nathan N; Shaharabani E; Shapira Z; Shabthai E; Mor E
INSTITUCIÓN
/ INSTITUTION: - Department of Transplantation, Rabin
Medical Center, Beilinson Campus, Petah-Tiqwa, Israel. rutir@clalit.org.il
----------------------------------------------------
[127]
TÍTULO / TITLE: - B19 virus infection in
renal transplant recipients.
REVISTA
/ JOURNAL: - J Clin Virol. Acceso gratuito al texto
completo.
●●
Enlace a la Editora de la Revista http://www.elsevier.com/gej-ng/29/46/32/show/Products/VIRUSINT/index.htt
●●
Cita: J Clinical Virology: <> 2003 Apr;26(3):361-8.
AUTORES
/ AUTHORS: - Cavallo R; Merlino C; Re D; Bollero C;
Bergallo M; Lembo D; Musso T; Leonardi G; Segoloni GP; Ponzi AN
INSTITUCIÓN
/ INSTITUTION: - Virology Unit, Department of Public Health
and Microbiology, University of Turin, Via Santena 9, 10126, Turin, Italy. rossana.cavallo@unito.it
RESUMEN
/ SUMMARY: - BACKGROUND: B19 virus infection with
persistent anaemia has been reported in organ transplant recipients. Detection
of B19 virus DNA in serum is the best direct marker of active infection.
OBJECTIVE: The present study evaluated the incidence and clinical role of
active B19 virus infection in renal transplant recipients presenting with
anaemia. STUDY DESIGN: Forty-eight such recipients were investigated by nested
PCR on serum samples. The controls were 21 recipients without anaemia. Active
HCMV infection was also investigated as a marker of high immunosuppression.
RESULTS AND CONCLUSIONS: In 11/48 (23%) patients B19 virus DNA was demonstrated
in serum versus only 1/21 (5%) of the controls. Ten of these 11 patients had
already been seropositive at transplantation and active infection occurred in
eight of them during the first 3 months after transplantation. The remaining
patient experienced a primary infection 9 months after transplantation. Eight
(73%) of these 11 patients displayed a concomitant HCMV infection and four
(36%) showed increasing serum creatinine levels but none developed
glomerulopathy; 3/11 (27%) recovered spontaneously from anaemia whereas 8/11
(73%) needed therapy. In conclusion, the relatively high occurrence (23%) of
B19 virus infection in patients presenting with anaemia, suggests that it
should be considered in the differential diagnosis of persistent anaemia in
renal transplant recipients. Presence of the viral DNA should be assessed early
from transplantation and the viral load should be monitored to follow
persistent infection and better understand the relation between active
infection and occurrence of anaemia, and to assess the efficacy of IVIG therapy
and/or immunosuppression reduction in clearing the virus. N. Ref:: 56
----------------------------------------------------
[128]
TÍTULO / TITLE: - A mitochondrial
perspective on cell death.
REVISTA
/ JOURNAL: - Trends Biochem Sci 2001 Feb;26(2):112-7.
AUTORES
/ AUTHORS: - Bernardi P; Petronilli V; Di Lisa F; Forte
M
INSTITUCIÓN
/ INSTITUTION: - Dept. of Biomedical Sciences, Viale
Giuseppe Colombo 3, I-35121, Padova, Italy. bernardi@civ.bio.unipd.it
RESUMEN
/ SUMMARY: - The role of mitochondria as crucial
participants in cell death programs is well established, yet the mechanisms
responsible for the release of mitochondrial activators and the role of BCL2
family proteins in this process remain controversial. Here, we point out the
limitations of current approaches used to monitor the physiological responses
of mitochondria during cell death, the implications arising from modern views
of mitochondrial structure, and briefly assess two proposed mechanisms for the
release of mitochondrial proteins during apoptosis. N. Ref:: 50
----------------------------------------------------
[129]
TÍTULO / TITLE: - The Rapamune era of
immunosuppression 2003: the journey from the laboratory to clinical
transplantation.
REVISTA
/ JOURNAL: - Transplant Proc 2003 May;35(3
Suppl):18S-24S.
AUTORES
/ AUTHORS: - Camardo J
INSTITUCIÓN
/ INSTITUTION: - Wyeth Research, Collegeville, Pennsylvania
19426, USA.
RESUMEN
/ SUMMARY: - The story of Rapamune (sirolimus,
rapamycin) began with the isolation of an antibiotic from a soil sample sent to
Ayerst Laboratories in Montreal. More than 25 years later, sirolimus was
approved for use by transplant physicians in the United States. Development
programs for new drugs for transplantation face significant challenges. Four
key challenges were critical to the development of sirolimus as a drug for
transplantation: First, sirolimus was not intended to be an antirejection
agent. Second, sirolimus was not easy to make or purify into a palatable
substance for human use and the development of a pharmaceutical form was an
important and critical hurdle. Third, sirolimus showed potent antirejection
activity when tested in de novo allograft recipients, but the development
program required careful attention to its optimal use in multidrug transplant
regimens. Fourth, the clinical program approved in the United States was
rejected in Europe, and it was only with additional studies and a unique appeal
process that sirolimus became available in Europe. Currently, sirolimus
(Rapamune) is available throughout most of the world except in Japan, having
achieved regulatory approvals in North America, Europe, the Middle East, Latin
America, and Asia. Although sirolimus failed in its original role as an
antifungal agent, it ultimately succeeded as an antirejection drug. Today,
sirolimus holds additional promise both as a drug useful for the prevention of
restenosis after coronary angioplasty and as an antitumor agent. N. Ref:: 39
----------------------------------------------------
[130]
TÍTULO / TITLE: - Molecular diagnosis of
an Enterocytozoon bieneusi human genotype C infection in a moderately
immunosuppressed human immunodeficiency virus seronegative liver-transplant
recipient with severe chronic diarrhea.
REVISTA
/ JOURNAL: - J Clin Microbiol. Acceso gratuito al texto
completo a partir de los 6 meses de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://jcm.asm.org/
●●
Cita: J. Clinical Microbiology: <> 2001 Jun;39(6):2371-2.
AUTORES
/ AUTHORS: - Sing A; Tybus K; Heesemann J; Mathis
A N. Ref:: 5
----------------------------------------------------
[131]
TÍTULO / TITLE: - Eradication of
parvovirus B19 infection after renal transplantation requires reduction of
immunosuppression and high-dose immunoglobulin therapy.
REVISTA
/ JOURNAL: - Nephrol Dial Transplant. Acceso gratuito
al texto completo a partir de los 2 años de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://ndt.oupjournals.org/
●●
Cita: Nephrology Dialysis Transplantation: <> 2002 Oct;17(10):1840-2.
AUTORES
/ AUTHORS: - Liefeldt L; Buhl M; Schweickert B;
Engelmann E; Sezer O; Laschinski P; Preuschof L; Neumayer HH
INSTITUCIÓN
/ INSTITUTION: - Department of Nephrology, Charite,
Humboldt-University Berlin, Germany. lutz.liefeldt@charite.de N. Ref:: 17
----------------------------------------------------
[132]
- Castellano -
TÍTULO / TITLE:Presentacion de canceres en
receptores trasplantados con organo solido. Presentation of cancers in
recipients of a solid-organ transplant.
REVISTA
/ JOURNAL: - Nefrologia. Acceso gratuito al texto
completo.
●●
Enlace a la Editora de la Revista http://www.aulamedica.es/nefrologia/
●●
Cita: Nefrologia: <> 2001;21(6):528-37.
AUTORES
/ AUTHORS: - Lampreabe I; Gomez-Ullate P; Amenabar JJ;
Zarraga S; Gainza FJ; Urbizu JM
INSTITUCIÓN
/ INSTITUTION: - Servicio de Nefrologia, Hospital de
Cruces, Facultad de Medicina, Universidad del Pais Vasco. ilampreave@hcru.osakidetza.net N. Ref:: 35
----------------------------------------------------
[133]
TÍTULO / TITLE: - Recent advances in
immunosuppressive therapy for renal transplantation.
REVISTA
/ JOURNAL: - Semin Dial 2001 May-Jun;14(3):218-22.
AUTORES
/ AUTHORS: - Peddi VR; First MR
INSTITUCIÓN
/ INSTITUTION: - Division of Nephrology and Hypertension,
Department of Internal Medicine, University of Cincinnati College of Medicine,
Cincinnati, Ohio 45267-0585, USA. ram.peddi@uc.edu
RESUMEN
/ SUMMARY: - Recent advances in immunosuppression have
focused on more effective, safer, and targeted therapies that have resulted in
improved short- and intermediate-term renal allograft survival. During the past
decade there has been a marked decrease in acute rejection rates following
renal transplantation because of the use of newer immunosuppressive agents.
Recent data indicate that the average yearly reduction in the relative hazard
of graft failure beyond 1 year was 4.2% for all recipients (0.4% for those
recipients who had an acute rejection episode and 6.3% for those who did not
have an acute rejection). Despite these improvements the currently available
immunosuppressive agents are associated with significant cardiovascular risk
factors, an increased risk of infection, and the development of malignancies in
the long term. Predictive parameters of donor-specific hyporesponsiveness are
needed so as to allow identification of patients in whom immunosuppressive
therapy can be safely reduced. Immunosuppressive agents that have recently been
approved for use in the United States and those that are in clinical and
preclinical studies are discussed. N.
Ref:: 27
----------------------------------------------------
[134]
TÍTULO / TITLE: - Impact of immunosuppressive
therapy on recurrence of hepatitis C.
REVISTA
/ JOURNAL: - Liver Transpl 2002 Oct;8(10 Suppl
1):S19-27.
●●
Enlace al texto completo (gratuito o de pago) 1053/jlts.2002.35852
AUTORES
/ AUTHORS: - Everson GT
INSTITUCIÓN
/ INSTITUTION: - Hepatology, University of Colorado School
of Medicine, Denver, CO 80262, USA. greg.everson@ucshc.edu
RESUMEN
/ SUMMARY: - 1. Approximately 10% to 25% of hepatitis C
virus-infected recipients of liver allografts will develop cirrhosis within 5
years of transplantation; this acceleration of the natural history of hepatitis
C is caused in part by immunosuppression. 2. Risk factors for aggressive
recurrence, graft loss, and death are treated acute cellular rejection,
methylprednisolone pulse therapy, and use of OKT3. There appears to be no
consistent difference between cyclosporine and tacrolimus in their effects on
hepatitis C. 3. The benefit of steroid withdrawal, although commonly practiced
in transplant recipients with hepatitis C, has not been proven. 4.
Mycophenolate mofetil may show synergistic antiviral properties when used with
interferon; however, posttransplantation use has not been associated with
consistent beneficial or deleterious effects. 5. Effects of other agents, such
as sirolimus or interleukin-2-receptor antibodies, have not been adequately
defined. Early reports suggest that disease activity may be more aggressive
when these agents are constituents of the immunosuppressive regimen. N. Ref:: 54
----------------------------------------------------
[135]
TÍTULO / TITLE: - Limited dose monoclonal
IL-2R antibody induction protocol after primary kidney transplantation.
REVISTA
/ JOURNAL: - Am J Transplant 2002 Jul;2(6):568-73.
AUTORES
/ AUTHORS: - Ahsan N; Holman MJ; Jarowenko MV; Razzaque
MS; Yang HC
INSTITUCIÓN
/ INSTITUTION: - Nephrology and Transplant Division,
University of Medicine and Dentistry of New Jersey, New Brunswick 08904, USA. ahsanna@umdnj.edu
RESUMEN
/ SUMMARY: - This study prospectively compared
immunoprophylaxis with a single intraoperative dose (2 mg/kg) of monoclonal
interleukin-2 receptor (IL-2R) antibody vs. noninduction in kidney transplant
recipients treated with tacrolimus (FK 506), mycophenolate mofetil (MMF) and a
prednisone-based immunosuppression regimen. One hundred recipients of
first-kidney transplant were enrolled into the study to receive either
anti-IL-2R monoclonal antibody, daclizumab (2 mg/kg intraoperatively, limited
anti-IL-2R) or no induction (control). Each patient also received oral
tacrolimus (dosed to target trough level 10-15 ng/mL), MMF (500 mg bid) and
prednisone. The primary efficacy end-point was the incidence of biopsy proven
acute rejection during the first 6 months post-transplant. The patients were
also followed for 12-month graft function, and graft and patient survival
rates. Other than the donor’s age being significantly lower in the control
group, both groups were comparable with respect to age, weight, gender, race,
human leukocyte antigen (HLA)-DR mismatch, panel reactive antibody (%PRA), cold
ischemic time, cytomegalovirus (CMV) status, causes of renal failure, and
duration and modes of renal replacement therapy (RRT). During the first 6
months, episodes of first biopsy confirmed acute rejection was 3/50 (6%) in the
limited anti-IL-2R group and 8/50 (16%) in the controls (p < 0.05).
Twelve-month patient 100/98 (%) and graft survival 100/96 (%) were not
statistically different. The group receiving limited anti-IL-2R did not have
any adverse reactions. Our study demonstrates that a limited (single) 2 mg/kg
immunoprophylaxis dose with monoclonal IL-2R antibody (daclizumab) when
combined with tacrolimus/MMF/steroid allows significant reduction in early
renal allograft rejection to the single digit level. The therapy with
anti-IL-2R antibody is simple and is well tolerated.
----------------------------------------------------
[136]
TÍTULO / TITLE: - The utility of
monoclonal antibody therapy in renal transplantation.
REVISTA
/ JOURNAL: - Transplant Proc 2002 May;34(3):797-800.
AUTORES
/ AUTHORS: - Loertscher R
INSTITUCIÓN
/ INSTITUTION: - Division of Transplantation, McGill
University Health Centre, Montreal, Quebec, Canada. rolf.loertscher@mcgill.ca N. Ref:: 37
----------------------------------------------------
[137]
TÍTULO / TITLE: - Safety and efficacy of
TOR inhibitors in pediatric renal transplant recipients.
REVISTA
/ JOURNAL: - Am J Kidney Dis 2001 Oct;38(4 Suppl
2):S22-8.
AUTORES
/ AUTHORS: - Ettenger RB; Grimm EM
INSTITUCIÓN
/ INSTITUTION: - Department of Pediatrics, Mattel
Children’s Hospital at UCLA, Los Angeles, CA 90095-1752, USA. Rettenger@mednet.ucla.edu
RESUMEN
/ SUMMARY: - Information about the pharmacokinetics,
safety, and efficacy of target of rapamycin (TOR) inhibitors, such as sirolimus
and everolimus, in pediatric renal transplant recipients is limited. In an
ascending single-dose pharmacokinetic study of sirolimus in pediatric dialysis
patients, no clinically significant association was observed between patient
age and absorption of sirolimus from the gastrointestinal tract. However, young
pediatric patients (5 to 11 years of age) exhibited significantly greater
apparent oral clearances, suggesting that pediatric patients require slightly
higher doses than do adults when adjusted for body weight or surface area.
Similarly, in studies performed in pediatric renal transplant recipients, the
half-life of sirolimus was shorter and the clearance was greater in younger
patients. On the other hand, in single-dose pharmacokinetic studies of
everolimus, the apparent clearance was reduced in pediatric renal transplant
recipients compared with clearance in adults. This reduced clearance was
attributed to a smaller apparent volume of distribution in pediatric patients,
rather than to a difference in terminal half-life. This suggested that, although
the adult 12-hour dosing interval was appropriate for pediatric patients, they
would require reduced dosing based on body size compared with adults. In a
large trial (N = 719) of sirolimus versus azathioprine in combination with
cyclosporine microemulsion and prednisone, 6 pediatric patients (13 to 18 years
of age) received sirolimus at 2 mg/d, 3 received sirolimus at 5 mg/d, and 3
received azathioprine. Seven of the nine patients who received sirolimus
experienced no rejection episodes. Six infectious episodes occurred in the 6
patients receiving sirolimus at 2 mg/d, 10 episodes occurred in the 3 patients
receiving sirolimus at 5 mg/d, and 8 episodes occurred in the 3 patients
receiving azathioprine. At 6 months after transplantation, renal function was
similar in all 3 groups, although there was a statistically nonsignificant
increase in the group receiving sirolimus at 5 mg/d. The mean cholesterol and
triglyceride levels were generally comparable in all 3 groups. TOR inhibitors
are promising agents for the prevention of graft rejection in pediatric renal
transplant recipients, but more pharmacokinetic data are required to assess the
optimal dosing regimens in this population. In addition, further data are
needed on the efficacy and safety of TOR inhibitors in combination with other
agents in pediatric transplantation recipients to best assess the role of TOR
inhibition in corticosteroid and/or calcineurin inhibitor-sparing
regimens. N. Ref:: 13
----------------------------------------------------
[138]
TÍTULO / TITLE: - Low-intensity
hematopoietic stem-cell transplantation across human leucocyte antigen barriers
in dyskeratosis congenita.
REVISTA
/ JOURNAL: - Bone Marrow Transplant 2003
May;31(10):847-50.
●●
Enlace al texto completo (gratuito o de pago) 1038/sj.bmt.1703931
AUTORES
/ AUTHORS: - Dror Y; Freedman MH; Leaker M; Verbeek J;
Armstrong CA; Saunders FE; Doyle JJ
INSTITUCIÓN
/ INSTITUTION: - Marrow Failure and Myelodysplasia
Programme, Division of Haematology and Oncology, Department of Paediatrics, The
Hospital for Sick Children and the University of Toronto, Toronto, Ontario,
Canada.
RESUMEN
/ SUMMARY: - Since the results of conventional hematopoietic
stem-cell transplantation (HSCT) for patients with dyskeratosis congenita (DC)
are poor owing to the high incidence of transplant-related complications, we
explored the use of a low-intensity HSCT regimen. We report two children with
DC with severe cytopenia, who underwent successful HSCT from a matched
unrelated donor after conditioning with fludarabine, cyclophosphamide, and
antithymocyte globulin. Graft-versus-host-disease (GVHD) prophylaxis consisted
of corticosteroids and cyclosporin A. The regimen was well tolerated, no
significant transplant-related complications were observed, and engraftment was
rapid and complete. At 15 and 16 months after HSCT, the children were fully
engrafted, in excellent clinical condition, full-donor chimerism, and no signs
of GVHD. We conclude that a low-intensity regimen is sufficient to induce
durable engraftment using matched unrelated donor HSCT in DC patients, with
minimal 1-year transplant-related toxicity. Longer follow-up will determine
whether this regimen also reduces long-term toxicity. N. Ref:: 35
----------------------------------------------------
[139]
TÍTULO / TITLE: - Tacrolimus versus
cyclosporine after lung transplantation: a prospective, open, randomized
two-center trial comparing two different immunosuppressive protocols.
REVISTA
/ JOURNAL: - J Heart Lung Transplant 2001
May;20(5):511-7.
AUTORES
/ AUTHORS: - Treede H; Klepetko W; Reichenspurner H;
Zuckermann A; Meiser B; Birsan T; Wisser W; Reichert B
INSTITUCIÓN
/ INSTITUTION: - Ludwig-Maximilians-University, Munich,
Germany.
RESUMEN
/ SUMMARY: - BACKGROUND: The need for better
immunosuppressive protocols after lung transplantation led us to investigate
tacrolimus (Tac) in combination with mycophenolate mofetil (MMF) and steroids
or cyclosporine (CsA) in combination with MMF and steroids in a prospective,
open, randomized trial after lung transplantation. METHODS: Between September
1997 and April 1999, 50 lung transplant recipients were randomized to receive
either Tac (n = 26) or CsA (n = 24) in combination with MMF and steroids. All
patients underwent induction therapy with rabbit antithymocyte globulin (ATG)
for 3 days. Freedom from acute rejection (AR), patient survival, infection
episodes, and side effects were monitored. RESULTS: There was no difference in
patient demographics between the two groups. Six-month and 1-year survival was
similar (84.6% and 73.1% in the Tac group vs 83.3% and 79.2% in the CsA group).
Freedom from AR at 6 months and 1 year after lung transplantation was slightly
higher in the Tac group (57.7% and 50% vs 45.8% and 33.3%, p = not significant
[n.s.]), whereas the number of treated rejection episodes per 100 patient days
in the Tac group was significantly lower (0.225 vs 0.426, p < .05). Four
patients in the CsA group had to be switched to Tac. Two patients in the CsA
group had to be retransplanted. Incidence of infections was similar in both
groups with a trend toward more fungal infections in the Tac group (n = 7 vs n
= 1, p = n.s.). CONCLUSIONS: The combination of Tac and MMF seems to have
slightly higher immunosuppressive potential compared with CsA and MMF. The
effectiveness of Tac as a rescue agent is not paralleled with undue signs of
overimmunosuppression.
----------------------------------------------------
[140]
TÍTULO / TITLE: - Vascular and cellular
mechanisms of chronic renal allograft dysfunction.
REVISTA
/ JOURNAL: - Transplantation 2001 Jun 15;71(11
Suppl):SS37-41.
AUTORES
/ AUTHORS: - Morris RE
INSTITUCIÓN
/ INSTITUTION: - Stanford University School of Medicine,
California, United States. N.
Ref:: 29
----------------------------------------------------
[141]
TÍTULO / TITLE: - Role of prostanoids and
endothelins in the prevention of cyclosporine-induced nephrotoxicity.
REVISTA
/ JOURNAL: - Prostaglandins Leukot Essent Fatty Acids
2001 Apr-May;64(4-5):231-9.
●●
Enlace al texto completo (gratuito o de pago) 1054/plef.2001.0265
AUTORES
/ AUTHORS: - Darlametsos IE; Varonos DD
INSTITUCIÓN
/ INSTITUTION: - Centre Franco-Hellenique de Recherches
Biomedicales, Nikolaos Papanikolaou, Corporation of the Municipality Agrinion,
Agrinion, 30100, Greece. darlamet@otenet.gr
RESUMEN
/ SUMMARY: - Cyclosporine A nephrotoxicity includes
both functional toxicity and histological changes, whose seriousness is
dependent upon the dose and the duration of the drug administration. Several
vasoactive agents have been found to be implicated in cyclosporine induced nephrotoxicity,
among which prostanoids and endothelins are the most important. In previous
studies we were able to prevent the early stage (7 days) of cyclosporine (37.4
micromol [45 mg]/kg/day) induced nephrotoxicity in rats either by the
administration, i) of OKY-046, a thromboxane A(2)synthase inhibitor, ii) of
ketanserine, an antagonist of S(2)serotonergic, a(1)adrenergic, and
H(1)histaminergic receptors and iii) of nifedipine, a calcium channel blocker,
or by diet supplementation either with evening primrose oil or fish oil. All
these protective agents elevated ratios of excreted renal prostanoid
vasodilators (prostaglandins E(2), 6ketoF(1 alpha)) to vasoconstrictor
(thromboxane B(2)), a ratio which was decreased by the administration of
cyclosporine alone. Nifedipine averted the cyclosporine induced increase of
urinary endothelin-1 release. All protections were associated with the
reinstatement of glomerular filtration rate forwards normal levels whereas
renal damage defence, consisting of a decrease of the cyclosporine induced
vacuolizations, was variable. Ketanserine and evening primrose oil were the
only agents which prevented the animal body weight loss. These data suggest
that prostanoids and endothelin-1 may mediate functional toxicity while thromboxane
A(2)is involved the morphological changes too, provoked in the early stage of
cyclosporine treatment. However, other nephrotoxic factors and additional
mechanisms could also be implicated in the cyclosporine induced nephrotoxicity. N. Ref:: 91
----------------------------------------------------
[142]
TÍTULO / TITLE: - Role of chiral
chromatography in therapeutic drug monitoring and in clinical and forensic
toxicology.
REVISTA
/ JOURNAL: - Ther Drug Monit 2002 Apr;24(2):290-6.
AUTORES
/ AUTHORS: - Williams ML; Wainer IW
INSTITUCIÓN
/ INSTITUTION: - Department of Oncology, Leicester
University, Leicester, United Kingdom.
RESUMEN
/ SUMMARY: - Advances in chiral chromatographic
separations have given pharmacologists and toxicologists the tools to examine
unexpected clinical results involving chiral drugs. The ability to unravel
complex phenomena associated with drug transport and drug metabolism is
presented in this manuscript. The relation between the chirality of the drug
mefloquine and the intracellular concentrations of the drug cyclosporine is
illustrated by examining the effect of the enantiomers of mefloquine on the
transport activity of P-glycoprotein (Pgp). These studies were conducted using
a liquid chromatographic column containing immobilized Pgp. The results
demonstrated that (+)-mefloquine competitively displaced the Pgp substrate
cyclosporine whereas (-)-mefloquine had no effect on cyclosporine-Pgp binding.
The data suggest that cyclosporine cellular and CNS concentrations can be increased
through the concomitant administration of (+)-mefloquine. The use of chirality
in clinical and forensic situations is also illustrated by the metabolism of
the enantiomers of ketamine (KET). The plasma concentrations of (+)-KET and
(-)-KET and the norketamine metabolites (+)-NK and (-)-NK were measured in rat
plasma using enantioselective gas chromatography. The separations were
accomplished using a gas chromatography chiral stationary phase based on
beta-cyclodextrin. The pharmacokinetic profiles of (+)-, (-)-KET and (+)-,
(-)-NK were determined in control and protein-calorie malnourished (PCM) rats
to determine the effect of PCM on ketamine metabolism and clearance. The
results indicate that PCM produced a significant and stereoselective decrease
in KET and NK metabolism. The data suggest that the effects of environmental
factors (smoking, alcohol use, diet) and drug interactions (coadministered
agents) can be measured using the changes in stereochemical metabolic and
pharmacokinetic patterns of KET and similar drugs. N. Ref:: 33
----------------------------------------------------
[143]
TÍTULO / TITLE: - Ten years of sirolimus
therapy in orthotopic liver transplant recipients.
REVISTA
/ JOURNAL: - Transplant Proc 2003 May;35(3
Suppl):209S-216S.
AUTORES
/ AUTHORS: - Neff GW; Montalbano M; Tzakis AG
INSTITUCIÓN
/ INSTITUTION: - University of Miami, Miami, Florida, USA.
RESUMEN
/ SUMMARY: - BACKGROUND: Sirolimus therapy has been
used in orthotopic liver transplant (OLT) recipients diagnosed with a variety
of diseases; chronic graft rejection (CR), calcineurin associated renal
toxicity, preemptive immune suppression, calcineurin related neurotoxicity,
preemptive therapy in transplant recipients with history of hepatocellular
carcinoma, and steroid resistant allograft rejection. METHODS: A search for the
medical literature and experiences involving sirolimus was done. RESULTS:
Several animal and human reports evaluating the use sirolimus in liver
transplant recipients are found and discussed. CONCLUSION: Sirolimus has been
used for multitude of indications, primarily based on anecdotal experiences.
However, reports of sirolimus related side effects have decreased the
transplant communities’ enthusiasm towards promoting this agent as a safe
immune suppression agent. N.
Ref:: 92
----------------------------------------------------
[144]
TÍTULO / TITLE: - Suggested guidelines
for the use of tacrolimus in cardiac transplant recipients.
REVISTA
/ JOURNAL: - J Heart Lung Transplant 2001
Jul;20(7):734-8.
AUTORES
/ AUTHORS: - Taylor DO; Barr ML; Meiser BM; Pham SM;
Mentzer RM; Gass AL
INSTITUCIÓN
/ INSTITUTION: - Department of Medicine, Division of
Cardiology, University of Utah, Salt Lake City, Utah 84132, USA. N. Ref:: 11
----------------------------------------------------
[145]
TÍTULO / TITLE: - Diffusion-weighted MR
imaging of posterior reversible leukoencephalopathy syndrome: a pictorial
essay.
REVISTA
/ JOURNAL: - Clin Imaging 2003 Sep-Oct;27(5):307-15.
AUTORES
/ AUTHORS: - Kinoshita T; Moritani T; Shrier DA;
Hiwatashi A; Wang HZ; Numaguchi Y; Westesson PL
INSTITUCIÓN
/ INSTITUTION: - Department of Radiology, Division of
Radiology, University of Rochester Medical Center, 601 Elmwood Avenue Box 648,
Rochester, NY 14642, USA. kino@grape.med.tottori-u.ac.jp
RESUMEN
/ SUMMARY: - Posterior reversible leukoencephalopathy
syndrome is characterized by reversible white matter lesions. However, ischemic
injury with irreversible damage may occur. This pictorial essay illustrates MR
features associated with posterior reversible leukoencephalopathy syndrome. We
will emphasize the role of diffusion-weighted imaging for the discrimination of
irreversible ischemic injury from reversible vasogenic edema. N. Ref:: 9
----------------------------------------------------
[146]
TÍTULO / TITLE: - Monitoring of cellular
resistance to cancer chemotherapy.
REVISTA
/ JOURNAL: - Hematol Oncol Clin North Am 2002
Apr;16(2):357-72, vi.
AUTORES
/ AUTHORS: - Krishan A; Arya P
INSTITUCIÓN
/ INSTITUTION: - Radiation Oncology Department, University
of Miami Medical School, Division of Experimental Therapeutics (R-71), P.O. Box
01690, Miami, FL 33101, USA. akrishan@med.miami.edu
RESUMEN
/ SUMMARY: - Cellular resistance to a broad spectrum of
natural products used as antitumor drugs is believed to be a major cause for
the failure of chemotherapy. Flow cytometry has been used for monitoring the
expression of drug resistance markers, determining accumulation of fluorescent
drugs, and for screening of drugs that enhance chemosensitivity by blocking
efflux and enhancing drug retention. This article reviews recent developments
in our understanding of the multiple drug resistance phenotype and the use of
flow cytometry for the study of drug efflux and its modulation in human tumor
cells. N. Ref:: 77
----------------------------------------------------
[147]
TÍTULO / TITLE: - Sirolimus therapy in
cardiac transplantation.
REVISTA
/ JOURNAL: - Transplant Proc 2003 May;35(3
Suppl):171S-176S.
AUTORES
/ AUTHORS: - Radovancevic B; Vrtovec B
INSTITUCIÓN
/ INSTITUTION: - Texas Heart Institute at St. Luke’s
Episcopal Hospital, Houston, Texas, USA.
RESUMEN
/ SUMMARY: - Rapamycin powerfully inhibits the
progression of antigen-activated T cells through the cell cycle. In animal
heart transplantation models, rapamycin therapy has been associated with
profound immunosuppressive effects on host humoral and cellular responses. In
consequence, further studies have been conducted to evaluate the efficiency of
rapamycin in preventing acute heart allograft rejection, treating refractory
acute heart allograft rejection, inducing transplantation tolerance, and
preventing and treating transplant coronary artery disease. The results of
these studies indicated that rapamycin can effectively prevent acute graft
rejection and inhibit refractory acute graft rejection in heart transplant
recipients by exerting potent immunosuppressive and antiproliferative effects without
adversely affecting renal function. This supports the use of rapamycin therapy
in heart transplant recipients, especially in those with renal dysfunction, for
whom treatment with calcineurin inhibitors is contraindicated. Rapamycin may
also halt and even reverse the progression of cardiac allograft vasculopathy,
which warrants further clinical trials in humans. Finally, rapamycin may be
able to induce transplantation tolerance, thus making it one of the most
promising modalities for improving the long-term survival of heart transplant
recipients. N. Ref:: 41
----------------------------------------------------
[148]
TÍTULO / TITLE: - Pimecrolimus (Elidel,
SDZ ASM 981)--preclinical pharmacologic profile and skin selectivity.
REVISTA
/ JOURNAL: - Semin Cutan Med Surg 2001
Dec;20(4):233-41.
AUTORES
/ AUTHORS: - Stuetz A; Grassberger M; Meingassner JG
INSTITUCIÓN
/ INSTITUTION: - Novartis Research Institute, Vienna,
Austria.
RESUMEN
/ SUMMARY: - The ascomycin macrolactam derivative
pimecrolimus (Elidel, SDZ ASM 981; Novartis Pharma AG, Basel Switzerland) is a
cell-selective inhibitor of inflammatory cytokines specifically developed for
the treatment of inflammatory skin diseases, such as atopic dermatitis,
allergic contact dermatitis, irritant contact dermatitis, and plaque-type
psoriasis. It inhibits the production of inflammatory cytokines in T cells and
mast cells and prevents the release of preformed inflammatory mediators from
mast cells. Topically administered pimecrolimus is as effective as the high-potency
corticosteroid clobetasol-17-propionate in a pig model of allergic contact
dermatitis (ACD). Unlike clobetasol, however, it does not cause skin atrophy.
Given orally, pimecrolimus is as potent or superior to tacrolimus (FK 506) in
treating ACD in mice and rats. Pimecrolimus also effectively reduces skin
inflammation and pruritus in hypomagnesemic hairless rats, a model that mimics
acute signs of atopic dermatitis. Pimecrolimus shows only a low potential to
impair systemic immune responses when compared with tacrolimus as shown in rats
in (1) the localized graft-versus-host reaction, (2) the antibody formation to
sheep red blood cells, and (3) kidney transplantation. Pimecrolimus permeates
through pig skin in vitro at a 10-times lower rate than tacrolimus, indicating
a lower potential for percutaneous absorption in vivo. The data suggest that
pimecrolimus combines high anti-inflammatory activity in the skin with a low
potential to impair systemic immune reactions.
N. Ref:: 31
----------------------------------------------------
[149]
TÍTULO / TITLE: - Molecular actions of
sirolimus: sirolimus and mTor.
REVISTA
/ JOURNAL: - Transplant Proc 2003 May;35(3
Suppl):227S-230S.
AUTORES
/ AUTHORS: - Kirken RA; Wang YL
INSTITUCIÓN
/ INSTITUTION: - Department of Integrative Biology and
Pharmacology, The University of Texas Health Science Center at Houston,
Houston, Texas 77030, USA. robert.a.kirken@uth.tmc.edu
RESUMEN
/ SUMMARY: - Recent therapeutic strategies to combat
organ allograft rejection have focused on T-cell signaling pathways and the
molecules that comprise them. The macrolide antibiotic produced by the
bacterium Streptomyces hygroscopicus, known as sirolimus or rapamycin, has
shown great therapeutic potential in the transplant setting. Sirolimus alone or
in combination with other immunosuppressive agents can block acute rejection,
chronic graft destruction, and promote permanent allograft acceptance.
Sirolimus targets a unique serine-threonine kinase, mammalian target of
rapamycin (mTor), which plays a key role in mitogenic and nutritional cells
signals. Within T cells, mTor regulates a number of proteins likely dependent
on T cell growth factors such as interleukin 2. This review is focused on the
molecular mechanisms by which mTor may regulate T-cell signaling cascades and
affect T-cell responsiveness, and how sirolimus likely uncouples this
activity. N. Ref:: 32
----------------------------------------------------
[150]
TÍTULO / TITLE: - The treatment of atopic
dermatitis with systemic immunosuppressive agents.
REVISTA
/ JOURNAL: - Clin Dermatol 2003 May-Jun;21(3):225-40.
AUTORES
/ AUTHORS: - Akhavan A; Rudikoff D
INSTITUCIÓN
/ INSTITUTION: - Department of Dermatology, Mount Sinai
School of Medicine, New York, New York 10029, USA. N. Ref:: 165
----------------------------------------------------
[151]
TÍTULO / TITLE: - Retroviral oncogenes
and TOR.
REVISTA
/ JOURNAL: - Curr Top Microbiol Immunol
2004;279:321-38.
AUTORES
/ AUTHORS: - Aoki M; Vogt PK
INSTITUCIÓN
/ INSTITUTION: - Department of Molecular and Experimental
Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road,
BCC-239, La Jolla, CA 92037, USA.
RESUMEN
/ SUMMARY: - Retroviruses have recruited the catalytic
subunit of PI 3-kinase and its downstream target, Akt, as oncogenes. These
viruses cause tumors in animals and induce oncogenic transformation in cell
culture. The oncogenicity of these viruses is specifically inhibited by
rapamycin; retroviruses carrying other oncogenes are insensitive to this
macrolide antibiotic. Rapamycin is an inhibitor of the TOR (target of
rapamycin) kinase whose downstream targets include p70 S6 kinase and the
negative regulator of translation initiation 4E-BP. Emerging evidence suggests
that the TOR signals transmitted to the translational machinery are essential
for oncogenic transformation by the PI 3-kinase pathway. N. Ref:: 93
----------------------------------------------------
[152]
TÍTULO / TITLE: - Treatment of patients
with chronic idiopathic urticaria.
REVISTA
/ JOURNAL: - Clin Rev Allergy Immunol 2002
Oct;23(2):233-41.
AUTORES
/ AUTHORS: - Stanaland BE
INSTITUCIÓN
/ INSTITUTION: - Division of Allergy and Immunology,
University of South Florida Health Sciences Center, USA.
RESUMEN
/ SUMMARY: - Treatment of patients with chronic
idiopathic urticaria (CIU) involves reducing symptoms with the least invasive
therapy and carefully balancing risk and benefit. The mainstay of therapy is
the use of antihistamines with or without the use of intermittent pulses of
corticosteroids. Alternative therapies to chronic corticosteroids include
leukotriene antagonists, plasma-phoresis, dapsone, stanazolol,
hydroxychloroquine, methotrexate, cyclosporin, tacrolimus, and warfarin. A practical
approach to CIU bases treatment and severity on the patients’ previous response
to therapy. Therapy goals are to reduce symptoms until spontaneous resolution
occurs. Management of CIU patients can be both frustrating and rewarding. N. Ref:: 34
----------------------------------------------------
[153]
TÍTULO / TITLE: - Programmed death in
yeast as adaptation?
REVISTA
/ JOURNAL: - FEBS Lett. Acceso gratuito al texto
completo a partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.elsevier.com/febs/show/index.htt
●●
Cita: FEBS Letters: <> 2002 Sep 25;528(1-3):23-6.
AUTORES
/ AUTHORS: - Skulachev VP
INSTITUCIÓN
/ INSTITUTION: - Belozersky Institute of Physico-Chemical
Biology, Moscow State University, Russia. skulach@belozersky.msu.ru
RESUMEN
/ SUMMARY: - During recent years, several pieces of
indirect evidence of a programmed death in yeast have been published. Among
them there are observations that some mammalian pro- or anti-apoptotic proteins
induce or prevent the death of yeast; some toxic compounds kill yeast at lower
concentrations if protein synthesis is operative; this death, as well as the
death due to certain mutations, shows some apoptotic markers. In April 2002,
the yeast programmed death concept received direct support. Madeo et al. [Madeo
et al., Mol. Cell 9 (2002) 911-917] disclosed a caspase which is activated by
H(2)O(2) or aging and is required for the protein-synthesis-dependent death of
yeast. Thus, a specific apoptosis-mediating protein was identified for the
first time in Saccharomyces cerevisiae. Independently, Severin and Hyman
[Severin, F.F., Hyman, A.A., Curr. Biol. 12 (2002) R233-R235] discovered that
death of yeast, induced by a high level of a pheromone, is programmed. In
particular, the death was found to be prevented by cycloheximide and
cyclosporin A. It required mitochondrial DNA, cytochrome c and the
pheromone-initiated protein kinase cascade. When haploids of opposite mating
types were mixed, some cells died, the inhibitory pattern being the same as in
the case of the killing by pheromone. Inhibition of mating proved to be
favorable for death. Thus, pheromone not only activates mating but also
eliminates yeast cells failing to mate. Such an effect should (i) stimulate
switch of the yeast population from vegetative to sexual reproduction, and (ii)
shorten the life span and, hence, accelerate changing of generations. As a
result, the probability of appearance of new traits could be enhanced when
ambient conditions turned for the worse.
N. Ref:: 40
----------------------------------------------------
[154]
TÍTULO / TITLE: - Intestinal graft-versus-host
disease: mechanisms and management.
REVISTA
/ JOURNAL: - Drugs 2003;63(1):1-15.
AUTORES
/ AUTHORS: - Takatsuka H; Iwasaki T; Okamoto T;
Kakishita E
INSTITUCIÓN
/ INSTITUTION: - Second Department of Internal Medicine,
Hyogo College of Medicine, Hyogo, Japan. hematol@hyo-med.ac.jp
RESUMEN
/ SUMMARY: - Allogeneic haematopoietic stem cell
transplantation remains the treatment of choice for a number of malignancies.
However, graft-versus-host disease (GVHD) has long been regarded as a serious
complication of this procedure. Although GVHD may affect any organ, intestinal
GVHD is particularly important because of its frequency, severity and impact on
the general condition of the patient. Recent studies have led to progressive
elucidation of the mechanism of GVHD. Donor T cells are critical for the
induction of GVHD, because depletion of T cells from bone marrow grafts
effectively prevents GVHD but also results in an increase of leukaemia relapse.
It has been shown that the gastrointestinal tract plays a major role in the
amplification of systemic disease because gastrointestinal damage increases the
translocation of endotoxins, which promotes further inflammation and additional
gastrointestinal damage. Consequently, the management of intestinal GVHD (and
the intestine itself) is a subject that should be highlighted. In this article,
approaches to the prevention of intestinal GVHD are discussed after being
classified into three categories: regimens in common clinical use, regimens
under investigation and original regimens used at our hospital. The standard
regimen that is used most widely for prevention of GVHD is cyclosporin plus
short-term methotrexate. Corticosteroids can be added to this regimen but careful
consideration of the adverse effects of these hormones should be considered.
Tacrolimus is a newer, more potent alternative to cyclosporin. T-cell depletion
(TCD) after transplantation has been shown to prevent acute GVHD, however, the
survival benefit of TCD has not been as great as expected. Mycophenolate
mofetil can be useful for the treatment of acute GVHD as part of combination
therapy. Regimens currently under investigation in animal experiments include
suppression of inflammatory cytokines and inhibition of T-cell activation, and,
specifically at our institution, hepatocyte growth factor gene therapy. The
evidence-based therapy used at our institution includes systemic antibacterial
therapy (including eradication of intestinal bacteria) to prevent the
intestinal translocation of lipopolysaccharide and avoid the subsequent
increase of various inflammatory cytokines. In addition, because of the
similarities between intestinal GVHD and ulcerative colitis, sulfasalazine,
betamethasone enemas and eicosapentaenoic acid have been used to treat
intestinal GVHD in some patients. N.
Ref:: 125
----------------------------------------------------
[155]
TÍTULO / TITLE: - Prevention strategies
for type 1 diabetes mellitus: current status and future directions.
REVISTA
/ JOURNAL: - BioDrugs 2003;17(1):39-64.
AUTORES
/ AUTHORS: - Winter WE; Schatz D
INSTITUCIÓN
/ INSTITUTION: - Department of Pathology, University of
Florida, Gainesville, Florida 32610, USA. winter@pathology.ufl.edu
RESUMEN
/ SUMMARY: - Type 1 diabetes mellitus affects about 1
in 300 people in North America and Europe. Epidemiological studies indicate
that the incidence and thus prevalence of type 1 diabetes is rising worldwide.
Intervention in autoimmune type 1a diabetes could occur at the time of
diagnosis or, preferably, prior to clinical presentation during the
‘prediabetic’ period (e.g. prevention). Prediabetes is best recognised by the
detection of islet autoantibodies in the serum. Promising intervention
strategies include monoclonal antibody therapies (e.g. anti-CD3, anti-CD25,
anti-CD52 or anti-CD20 monoclonal antibodies), immunosuppression (e.g.
calcineurin inhibitors, B7 blockade, glucocorticoids, sirolimus (rapamycin),
azathioprine or mycophenolate mofetil), immunomodulatory therapies (e.g.
plasmapheresis, intravenous immunoglobulin, cytokine administration, adoptive
cellular gene therapy) and tolerisation interventions (e.g. autoantigen
administration or avoidance, altered peptide ligand or peptide-based
therapies). To date, islet and pancreas transplantation have essentially been
reserved for patients with long-standing diabetes who have complications and
are also in need of a concurrent kidney transplant. None of the therapies
attempted to date has produced long-term remissions in new-onset type 1
diabetes patients and no therapies have been shown to prevent the disease.
Nevertheless, with advances in our understanding of basic immunology and the
cellular and molecular mechanisms of tolerance induction and maintenance,
successful intervention therapies will be developed. The balance between safety
and efficacy is critical. Higher rates of adverse events might be more
tolerable in new-onset type 1 diabetes patients if the therapy is extremely
effective at inducing a permanent remission. However, therapies must not harm
the beta-cells themselves or any organ system that is a potential target of
diabetes complications, such as the nervous system, retina, cardiovascular
system or kidney. In the treatment of prediabetes, successful therapies should
provide a level of safety similar to that of currently used vaccines and a high
level of efficacy. N.
Ref:: 244
----------------------------------------------------
[156]
TÍTULO / TITLE: - Regulation of MAPK
signaling pathways through immunophilin-ligand complex.
REVISTA
/ JOURNAL: - Curr Top Med Chem 2003;3(12):1358-67.
AUTORES
/ AUTHORS: - Matsuda S; Koyasu S
INSTITUCIÓN
/ INSTITUTION: - Department of Microbiology and Immunology,
Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo
160-8582, Japan.
RESUMEN
/ SUMMARY: - It is well established that the
immunosuppressive effects of cyclosporin A (CsA) and FK506 (also known as
tacrolimus) are mediated through binding to their cognate cellular proteins
cyclophilin and FKBP (collectively termed immunophilins), respectively.
Biochemical analysis had revealed that cyclophilin-CsA and FKBP-FK506 complexes
bind to and inactivate Ca(2+)-dependent serine/threonine phosphatase
calcineurin. Since calcineurin regulates nuclear translocation and subsequent
activation of nuclear factor of activated T cells (NFAT) transcription factors
that is one of essential steps for cytokine gene expression in activated T
cells, it is believed that inhibition of calcineurin is a molecular basis of
the immunosuppressive properties of CsA and FK506. However, recent studies
indicate that both CsA and FK506 can block activation of JNK and p38 signaling
pathways during T cell activation. CsA and FK506, thus, have two distinct
mechanisms of action; one is the inhibition of the protein phosphatase activity
of calcineurin, leading to the blockade of the nuclear translocation of NFAT
transcription factors, and the other is the suppression of JNK and p38
activation pathways. It is likely that the presence of two distinct targets in
T cell activation makes CsA and FK506 highly potent immunosuppressive drugs.
Here we discuss the action of immunophilin-ligand complexes on JNK and p38
activation pathways. We also argue the possibility of immunotherapeutic
application targeting at JNK and p38 signaling pathways. N. Ref:: 121
----------------------------------------------------
[157]
TÍTULO / TITLE: - Tailoring
immunosuppressive therapy based on donor and recipient risk factors.
REVISTA
/ JOURNAL: - Transplant Proc 2001 May;33(3):2207-11.
AUTORES
/ AUTHORS: - First MR
INSTITUCIÓN
/ INSTITUTION: - University of Cincinnati Medical Center,
Cincinnati, Ohio 45267-0585, USA. N.
Ref:: 35
----------------------------------------------------
[158]
TÍTULO / TITLE: - Cytokine and
immunosuppressive therapies of type 1 diabetes mellitus.
REVISTA
/ JOURNAL: - Endocrinol Metab Clin North Am 2002
Jun;31(2):477-95.
AUTORES
/ AUTHORS: - Gottlieb PA; Hayward AR
INSTITUCIÓN
/ INSTITUTION: - Barbara Davis Center for Childhood
Diabetes, Department of Pediatrics, University of Colorado Health Sciences
Center, Box B140, 4200 East 9th Ave., Denver, CO 80262, USA.
RESUMEN
/ SUMMARY: - In this article, the authors covered a
number of issues that affect how researchers approach prevention of diabetes.
The focus has been the use of cytokines and immunosuppressive therapies. The
historical understanding of cytokine and immunosuppressive approaches, new
developments in using these agents in humans, and the issues involved in
designing diabetes prevention trials were reviewed. Although progress at times
appears slow, the current research activities predict new developments in the
next few years that may improve the understanding of the progression of diabetes
and possible ways to intervene. N.
Ref:: 79
----------------------------------------------------
[159]
TÍTULO / TITLE: - Maintenance
immunosuppression in the renal transplant recipient: an overview.
REVISTA
/ JOURNAL: - Am J Kidney Dis 2001 Dec;38(6 Suppl
6):S25-35.
AUTORES
/ AUTHORS: - Gaston RS
INSTITUCIÓN
/ INSTITUTION: - Division of Nephrology, University of
Alabama at Birmingham, Birmingham, AL 35294, USA. rgaston@nrtc.uab.edu
RESUMEN
/ SUMMARY: - Managing maintenance immunosuppressive
regimens after kidney transplantation is often challenging and confusing,
requiring careful attention to efficacy, dosing, adverse effects, and costs of
multiple medications. Most protocols combine a primary immunosuppressant
(cyclosporine or tacrolimus) with one or two adjunctive agents (azathioprine,
mycophenolate mofetil, sirolimus, corticosteroids). Avoiding drug-drug
interactions is a major part of effective immunosuppressant management, and
special situations (eg, pregnancy, intravenous dosing, caring for minority
patients) can prove especially daunting. This review summarizes available data
regarding current practices in maintenance immunosuppression, emphasizing
issues that arise in day-to-day management of renal transplant recipients. N. Ref:: 69
----------------------------------------------------
[160]
TÍTULO / TITLE: - Regulation of
endothelial-type NO synthase expression in pathophysiology and in response to
drugs.
REVISTA
/ JOURNAL: - Nitric Oxide 2002 Nov;7(3):149-64.
AUTORES
/ AUTHORS: - Li H; Wallerath T; Munzel T; Forstermann U
INSTITUCIÓN
/ INSTITUTION: - Department of Pharmacology, Johannes
Gutenberg University, Obere Zahlbacher Strasse 67, D-55101, Mainz, Germany.
RESUMEN
/ SUMMARY: - In many types of cardiovascular
pathophysiology such as hypercholesterolemia and atherosclerosis, diabetes,
cigarette smoking, or hypertension (with its sequelae stroke and heart failure)
the expression of endothelial NO synthase (eNOS) is altered. Both up- and
downregulation of eNOS have been observed, depending on the underlying disease.
When eNOS is upregulated, the upregulation is often futile and goes along with
a reduction in bioactive NO. This is due to an increased production of
superoxide generated by NAD(P)H oxidase and by an uncoupled eNOS. A number of
drugs with favorable effects on cardiovascular disease upregulate eNOS
expression. The resulting increase in vascular NO production may contribute to
their beneficial effects. These compounds include statins,
angiotensin-converting enzyme inhibitors, AT1 receptor antagonists, calcium
channel blockers, and some antioxidants. Other drugs such as glucocorticoids,
whose administration is associated with cardiovascular side effects,
downregulate eNOS expression. Stills others such as the immunosuppressants
cyclosporine A and FK506/tacrolimus or erythropoietin have inconsistent effects
on eNOS. Thus regulation of eNOS expression and activity contributes to the
overall action of several classes of drugs, and the development of compounds
that specifically upregulate this protective enzyme appears as a desirable
target for drug development. N.
Ref:: 201
----------------------------------------------------
[161]
TÍTULO / TITLE: - What’s in the pipeline?
New immunosuppressive drugs in transplantation.
REVISTA
/ JOURNAL: - Am J Transplant 2002 Nov;2(10):898-903.
AUTORES
/ AUTHORS: - Vincenti F
INSTITUCIÓN
/ INSTITUTION: - University of California, San Francisco,
Kidney Transplant Service, 505 Parnassus Avenue, Room 884M, San Francisco, CA
94143-0116, USA. vincentif@surgery.ucsf.edu
RESUMEN
/ SUMMARY: - In the pipeline, there are a number of
novel immunosuppressive drugs in preclinical development or in early clinical
trials. The major target of new agents are cell-surface molecules important in
immune cell interactions (especially the costimulatory pathway), signaling
pathways that activate T cells, T-cell proliferation and trafficking and
recruitment of immune cells responsible for rejection. The most promising
biologic agents include a humanized anti-CD11a (anti-LFA1), humanized
anti-B7.1/B7.2, a second-generation CTLA4Ig (LEA29Y) and a humanized antibody
to anti-CD45 RB. Inhibitors of T-cell activation and signaling are still in
preclinical development. The most interesting inhibitors of T-cell
proliferation include inhibitors of the Janus protein tyrosine kinase, JAK3,
and FK778, a leflunomide analog. Chemokines play an important role in rejection
by virtue of their critical role as regulator of trafficking and activation of
lymphocytes. Early trials of FTY720, a synthetic small molecule with functional
homology to sphingosine-1 phosphate leading to lymphocyte sequestration, appear
very promising; however, enthusiasm for this drug is mitigated by its potential
cardiac side-effects. Antagonists to several chemokine receptors, including
CCR1, CXCR3 and CCR5, have been shown to be effective in experimental
transplantation and are likely to be considered for clinical development. N. Ref:: 46
----------------------------------------------------
[162]
TÍTULO / TITLE: - Current and potential
agents for the treatment of alopecia areata.
REVISTA
/ JOURNAL: - Curr Pharm Des 2001 Feb;7(3):213-30.
AUTORES
/ AUTHORS: - Freyschmidt-Paul P; Hoffmann R; Levine E;
Sundberg JP; Happle R; McElwee KJ
INSTITUCIÓN
/ INSTITUTION: - Department of Dermatology, Philipp
University, Marburg, Germany. freyschm@mailer.uni-marburg.de
RESUMEN
/ SUMMARY: - Alopecia areata is considered to be a
T-cell mediated autoimmune disease of the hair follicle. Current
immunosuppressive approaches and immunomodulatory treatment with contact
sensitizers such as diphenylcyclopropenone and squaric acid dibutylester are
dealt with in this review article. The efficacy of the various modes of
treatment is evaluated by a review of literature and their mode of action is
discussed. In accordance with the mechanism of autoimmune pathogenesis of AA,
improved future treatments may be immunosuppressive or immunomodulatory, or
they should otherwise protect the hair follicle from the injurious effects of
the inflammation. Such possible future therapeutic approaches include the use
of liposomes as an improved vehicle, application of immunosuppressive cytokines
like TGF-beta and IL-10, inhibition of apoptosis mediated by the Fas-FasL
system, inhibition of the lymphocyte homing receptor CD44v10, induction of
tolerance as well as principles of gene therapy. N. Ref:: 141
----------------------------------------------------
[163]
TÍTULO / TITLE: - Tolerance to islet
autoantigens in type 1 diabetes.
REVISTA
/ JOURNAL: - Annu Rev Immunol 2001;19:131-61.
●●
Enlace al texto completo (gratuito o de pago) 1146/annurev.immunol.19.1.131
AUTORES
/ AUTHORS: - Bach JF; Chatenoud L
INSTITUCIÓN
/ INSTITUTION: - INSERM U 25, Hopital Necker, 161 rue de
Sevres, Paris Cedex 15, 75743 France. bach@necker.fr
RESUMEN
/ SUMMARY: - Tolerance to beta cell autoantigens
represents a fragile equilibrium. Autoreactive T cells specific to these
autoantigens are present in most normal individuals but are kept under control
by a number of peripheral tolerance mechanisms, among which CD4(+) CD25(+)
CD62L(+) T cell-mediated regulation probably plays a central role. The
equilibrium may be disrupted by inappropriate activation of
autoantigen-specific T cells, notably following to local inflammation that
enhances the expression of the various molecules contributing to antigen
recognition by T cells. Even when T cell activation finally overrides
regulation, stimulation of regulatory cells by CD3 antibodies may reset the
control of autoimmunity. Other procedures may also lead to disease prevention.
These procedures are essentially focused on Th2 cytokines, whether used
systemically or produced by Th2 cells after specific stimulation by
autoantigens. Protection can also be obtained by NK T cell stimulation.
Administration of beta cell antigens or CD3 antibodies is now being tested in
clinical trials in prediabetics and/or recently diagnosed diabetes. N. Ref:: 153
----------------------------------------------------
[164]
TÍTULO / TITLE: - Early experience using
calcineurin-free protocol in recipients of high-risk cadaver renal transplants.
REVISTA
/ JOURNAL: - Transplant Proc 2002 Aug;34(5):1627-8.
AUTORES
/ AUTHORS: - El-Sabrout R; Delaney V; Butt F; Qadir M;
Rashid I; Hanson P; Butt K
INSTITUCIÓN
/ INSTITUTION: - Departments of Transplantation/Vascular
Surgery, New York Medical College, Valhalla, New York, USA.
----------------------------------------------------
[165]
TÍTULO / TITLE: - Reactivation of
replication of hepatitis B and C viruses after immunosuppressive therapy: an
unresolved issue.
REVISTA
/ JOURNAL: - Lancet Oncol 2002 Jun;3(6):333-40.
AUTORES
/ AUTHORS: - Vento S; Cainelli F; Longhi MS
INSTITUCIÓN
/ INSTITUTION: - Section of Infectious Diseases, Department
of Pathology, University of Verona, Borgo Trento Hospital, Verona, Italy. ventosandro@yahoo.it
RESUMEN
/ SUMMARY: - The liver is susceptible to the toxic
effects of many cytotoxic or immunosuppressive treatments. However, in carriers
of hepatitis B virus (HBV) and, less frequently, of hepatitis C virus, liver
damage due to reactivation of viral replication can occur after withdrawal of
immunosuppressive drugs. These reactivations, which are associated with
fulminant forms of hepatitis in up to 25% of cases, are observed both in
symptom-free chronic carriers of hepatitis B surface antigen and in patients
who have chronic hepatitis B or C and concurrent haematological tumours or
solid neoplasms or who have received transplants. HBV-related complications may
cause delays or modifications of therapy, and the chance of cure is reduced. In
this review, we analyse clinical, biochemical, and serological issues in
reactivation of viral replication and examine the role of immune reactions in
the pathogenesis and the possible toxicity of immunosuppressive drugs. We
emphasise the importance of identifying predictive markers of a clinically
relevant reactivation, review difficulties in drug prevention and treatment,
indicate studies that are needed to address the key clinical issues, and give
practical recommendations to practising physicians and oncologists. N. Ref:: 60
----------------------------------------------------
[166]
TÍTULO / TITLE: - Hepatitis B virus (HBV)
reactivation after cytotoxic or immunosuppressive therapy—pathogenesis and
management.
REVISTA
/ JOURNAL: - Rev Med Virol 2001 Sep-Oct;11(5):287-99.
●●
Enlace al texto completo (gratuito o de pago) 1002/rmv.322 [pii]
AUTORES
/ AUTHORS: - Xunrong L; Yan AW; Liang R; Lau GK
INSTITUCIÓN
/ INSTITUTION: - University Department of Medicine, Queen
Mary Hospital, 102 Pokfulum Road, Hong Kong SAR, China.
RESUMEN
/ SUMMARY: - In an endemic area for chronic hepatitis B
infection, reactivation of this virus is a serious cause of morbidity and
mortality in patients undergoing cytotoxic or immunosuppressive therapy.
Careful prospective serological testing has shown that hepatitis B virus
reactivation is a two-staged process. The initial stage occurs during intense
cytotoxic or immunosuppressive therapy and is characterised by enhanced viral
replication, as reflected by increases in the serum levels of hepatitis B virus
DNA, hepatitis B e antigen, hepatitis B virus DNA polymerase and infection of
naive hepatocytes with hepatitis B virus. The second stage is related to
restoration of immune function following withdrawal of cytotoxic or
immunosuppressive therapy, which causes rapid immune-mediated destruction of
infected hepatocytes. Clinically, this can lead to hepatitis, hepatic failure
and even death. The occurrence and severity of hepatitis B virus reactivation
after various cytotoxic or immunosuppressive therapy is unpredictable and
treatment has been disappointing, largely due to the late administration of
therapy. Recently, pre-emptive treatment of chronic hepatitis B patients
undergoing cytotoxic or immunosuppressive therapy, with potent nucleoside
analogues has shown some promising results. Further controlled studies are
needed to define the incidence and risk factors of hepatitis B reactivation so
that pre-emptive treatment with nucleoside analogues could be administered to
those patients at high risk of disease.
N. Ref:: 93
----------------------------------------------------
[167]
TÍTULO / TITLE: - The role of newer
monoclonal antibodies in renal transplantation.
REVISTA
/ JOURNAL: - Transplant Proc 2001
Feb-Mar;33(1-2):1000-1.
AUTORES
/ AUTHORS: - Vincenti F
INSTITUCIÓN
/ INSTITUTION: - University of California, San Francisco,
California, USA. N.
Ref:: 5
----------------------------------------------------
[168]
TÍTULO / TITLE: - Mechanisms of action of
therapeutics in idiopathic thrombocytopenic purpura.
REVISTA
/ JOURNAL: - J Pediatr Hematol Oncol 2003 Dec;25 Suppl
1:S52-6.
AUTORES
/ AUTHORS: - Cines DB; McKenzie SE; Siegel DL
INSTITUCIÓN
/ INSTITUTION: - University of Pennsylvania School of
Medicine, Department of Pathology and Laboratory Medicine, 513A Stellar-Chance,
422 Curie Boulevard, Philadelphia, PA 19104, USA. dcines@mail.med.upenn.edu
RESUMEN
/ SUMMARY: - Idiopathic thrombocytopenic purpura (ITP)
is a common immune disorder caused by platelet-reactive autoantibodies.
Antibody-coated platelets are cleared more rapidly from the circulation, often
in the spleen, than they can be replaced by compensatory stimulation of
platelet production in the bone marrow. In some patients, platelet production
is depressed as well. ITP in adults does not generally remit spontaneously, and
most patients require treatment to prevent bleeding at one time or another.
Therapy with corticosteroids, danazol, intravenous immune globulin, anti-D
antibody, and several other agents inhibits clearance of the antibody-coated
platelets but is rarely curative. Most patients will sustain a hemostatic
response after splenectomy, although relapses may occur at any time. Patients
may be more responsive to these same modalities after splenectomy, but
treatment with an immunosuppressant that inhibits T- and B-cell function and
cooperation, including azathioprine, cyclophosphamide, cyclosporine,
mycophenolate mofetil, or anti-CD20, may be required. Antiviral therapy is
useful in patients with HIV or hepatitis C infection, but no consensus has been
reached as to the efficacy of antibiotics to eradicate Helicobacter pylori.
Promising results have been seen in several patients treated with a modified
thrombopoietin. It may be possible to design therapeutics that exploit the
apparent restricted immunoglobulin gene usage by antiplatelet antibodies,
perhaps in the form of engineered anti-idiotypic antibodies or other compounds
that specifically target autoantibody-producing B cells. Rationale therapy awaits
a more thorough understanding of autoantibody production. N. Ref:: 46
----------------------------------------------------
[169]
TÍTULO / TITLE: - Advances in the
management of psoriasis: monoclonal antibody therapies.
REVISTA
/ JOURNAL: - Int J Dermatol 2002 Dec;41(12):827-35.
AUTORES
/ AUTHORS: - Mehrabi D; DiCarlo JB; Soon SL; McCall CO
INSTITUCIÓN
/ INSTITUTION: - Department of Dermatology, Emory
University School of Medicine, Atlanta, GA 30322, USA.
RESUMEN
/ SUMMARY: - Psoriasis is a common skin disorder
characterized by erythematous, scaling plaques. Until recently, therapies for
this disease have been aimed at reducing keratinocyte proliferation. We have
learned that psoriasis is not primarily a disorder of keratinocyte
hyperproliferation, but is an inflammatory disease. This knowledge, especially
our current understanding of the role of activated T cells in psoriasis, has
led to new therapeutic options and new areas of research. Immunosuppressive
agents such as cyclosporine have proven very useful in the treatment of
psoriasis, but their use is limited by toxicity. Monoclonal antibodies directed
against key components of the inflammatory process have been studied in an
attempt to produce safer, more selective immunosuppressive agents. This review
summarizes much of the available literature describing the use of monoclonal
antibodies in the treatment of psoriasis.
N. Ref:: 59
----------------------------------------------------
[170]
TÍTULO / TITLE: - Molecular mechanisms of
renal allograft fibrosis.
REVISTA
/ JOURNAL: - Br J Surg 2001 Nov;88(11):1429-41.
●●
Enlace al texto completo (gratuito o de pago) 1046/j.0007-1323.2001.01867.x
AUTORES
/ AUTHORS: - Waller JR; Nicholson ML
INSTITUCIÓN
/ INSTITUTION: - Division of Transplant Surgery, University
of Leicester, Leicester, UK. julian@waller79.fsnet.co.uk
RESUMEN
/ SUMMARY: - BACKGROUND: Chronic graft nephropathy
(CGN) remains the leading cause of renal allograft loss after the first year
following transplantation. Histologically it is characterized by
glomerulosclerosis, intimal hyperplasia and interstitial fibrosis. The
pathogenesis is unclear, but is likely to involve both immunological and
non-immunological factors. Despite improvements in short-term graft survival
rates, new immunosuppressive regimens have made no impact on CGN. METHODS: A
review of the current literature on renal transplantation, novel
immunosuppression regimens and advances in the molecular pathogenesis of renal
allograft fibrosis was performed. RESULTS AND CONCLUSION: Recent advances in
understanding of the underlying molecular mechanisms involved suggest autocrine
secretion of cytokines and growth factors, especially transforming growth
factor beta, are associated with a change in fibroblast phenotype leading to
the deposition of extracellular matrix. Repeated insults trigger upregulation
of the tissue inhibitors of matrix metalloproteinases, favouring accumulation
of extracellular matrix. To date, no drug has proved effective in inhibiting or
reducing allograft fibrosis. The deleterious consequences of chronic
immunosuppression on the development of such fibrosis are now recognized; newer
immunosuppressive drugs, including rapamycin and mycophenolate mofetil, reduce profibrotic
gene expression in both experimental and clinical settings, and offer potential
strategies for prolonging allograft survival.
N. Ref:: 155
----------------------------------------------------
[171]
TÍTULO / TITLE: - Immunologic risk
factors for chronic renal allograft dysfunction.
REVISTA
/ JOURNAL: - Transplantation 2001 Jun 15;71(11
Suppl):SS17-23.
AUTORES
/ AUTHORS: - Paul LC
INSTITUCIÓN
/ INSTITUTION: - Leiden University Medical School, The
Netherlands.
RESUMEN
/ SUMMARY: - Tissue injury is probably the central
feature leading to CRAD, whether that injury is produced by immunological or
nonimmunological factors. Tissue injury may expose cryptic antigens that, in an
allogeneic situation, stimulate immune responses that further increase tissue
damage. With acute rejection the immunological factor most strongly predictive
of CRAD, HLA mismatches may facilitate rejection or otherwise lead to CRAD.
However, clinical studies have not always demonstrated an increasing risk of
CRAD with increased numbers of HLA mismatches. Antibodies produced against HLA
or other donor-specific antigens may play a role in initiating the CRAD process
or may occur secondary to tissue damage. Several human transplant studies have
demonstrated an association between anti-HLA or anti-B cell antibodies and
CRAD. In animal models of CRAD, antibodies are produced against antigens
associated with glomerular and tubular basement membranes and mesangial cells,
as well as antigens associated with vascular endothelial cells. The
pathogenetic significance of these antibody responses is unclear at this time,
but these responses may interfere with repair processes that follow tissue
injury or otherwise facilitate mechanisms leading to CRAD. Whether similar
antibody responses against components of basement membrane and mesangial cells
occur in human renal transplant patients with CRAD is not yet known. The most
effective way to prevent CRAD is to prevent tissue damage, especially
immunity-related injury that involves maintaining appropriate
immunosuppression. When using calcineurin inhibitors for immunosuppression,
there is a risk of chronic calcineurin inhibitor-associated nephrotoxicity.
Nonnephrotoxic immunosuppressive agents, such as sirolimus and mycophenolate
mofetil, may be considered in therapeutic strategies designed to prevent acute
rejection and to minimize renal tissue damage due to nephrotoxic drugs. N. Ref:: 54
----------------------------------------------------
[172]
TÍTULO / TITLE: - Daclizumab: a review of
its use in the management of organ transplantation.
REVISTA
/ JOURNAL: - BioDrugs 2001;15(11):745-73.
AUTORES
/ AUTHORS: - Carswell CI; Plosker GL; Wagstaff AJ
INSTITUCIÓN
/ INSTITUTION: - Adis International Limited, Auckland, New
Zealand. demail@adis.co.nz
RESUMEN
/ SUMMARY: - The humanised monoclonal antibody
daclizumab is an immunosuppressive agent that reduces acute rejection in solid
organ transplantation. It is specific for the alpha subunit (Tac/CD25) of the
interleukin (IL)-2 receptor on activated T cells and achieves immunosuppression
by competitive antagonism of IL-2-induced T cell proliferation. When added to
standard triple immunosuppression regimens, daclizumab significantly reduces
the rate of acute rejection at 1 year in renal transplantation by 36% and there
are indications that it may be effective in other solid organ transplantations.
Three-year outcomes of two phase III clinical trials in renal transplantation
indicate similar values for graft and patient survival between daclizumab and
placebo when given in addition to triple immunosuppression; however, these
pivotal trials were not designed with sufficient power to demonstrate any
statistical significance. The addition of daclizumab induction shows potential
in allowing calcineurin inhibitor- and corticosteroid-sparing regimens without
increasing the rate of acute graft rejection or adverse effects in renal and
liver transplantation. Preliminary reports indicate that daclizumab may also be
a useful agent in delayed graft function and graft versus host disease (GVHD).
Further investigation of its efficacy in these groups and in children is
needed. Data from clinical trials show daclizumab to be well tolerated in solid
organ transplantation. It does not increase the incidence of infection,
including cytomegalovirus infection, when compared with placebo or no induction
groups. Preliminary comparative data with muromonab CD3 indicate that
daclizumab may be associated with a lower rate of infectious complications and
similar or better efficacy. CONCLUSIONS: In conclusion, daclizumab has been
proven to reduce acute rejection in renal transplant recipients when given in
addition to traditional baseline immunosuppression. It has shown potential to
reduce acute rejection in other solid organ transplants; however, well
designed, randomised studies are required to confirm this. Clinical experience
from trials to date indicate that daclizumab has a tolerability profile similar
to placebo with no significant effect on the incidence of infection. The
relative efficacy and tolerability of daclizumab compared with other induction
agents has yet to be defined. Available data suggest that daclizumab may allow
the use of calcineurin inhibitor-sparing and corticosteroid-sparing regimens
and may have potential in the treatment of GVHD. N. Ref:: 80
----------------------------------------------------
[173]
TÍTULO / TITLE: - Neuroimmunophilin
ligands: the development of novel neuroregenerative/ neuroprotective compounds.
REVISTA
/ JOURNAL: - Curr Top Med Chem 2003;3(12):1368-75.
AUTORES
/ AUTHORS: - Gold BG; Villafranca JE
INSTITUCIÓN
/ INSTITUTION: - Center for Research on Occupational and
Environmental Toxicology, Developmental Biology, Oregon Health & Science
University, 3181 S.W. Sam Jackson Park Road, Portland, OR 97201-3098, USA. gold@ohsu.edu
RESUMEN
/ SUMMARY: - FK506 (tacrolimus), initially developed as
an immunosuppressant drug, represents a class of compounds with potential high
impact for the treatment of human neurological disorders. While
immunosuppression is mediated by the 12-kD FK506-binding-protein (FKBP-12), the
neurite elongation activity of FK506 involves FKBP-52 (also known as FKBP-59 or
Hsp-56), a component of mature steroid receptor complexes: FKBP-52 binds to
Hsp-90, which bind to p23 and the steroid receptor protein to form the complex.
The brief review focuses on how three classes of compounds (FK506 derivatives,
steroid hormones, and ansamycin anti-cancer drugs, e.g., geldanamycin) increase
neurite elongation/nerve regeneration (axonal elongation). A model is presented
whereby neurite elongation is elicited by compounds that bind to steroid
receptor chaperone proteins (e.g., FKBP-52 and Hsp-90) and thereby disrupt
mature steroid receptor complexes (comprising FKBP-52, Hsp-90 and p23 in
addition to the steroid receptor binding protein). Disruption of the complex
leads to a “gain-of-function” whereby one or more of these steroid receptor
chaperone proteins (i.e, FKBP-52, Hsp-90 or p23) activates mitogen-associated
protein (MAP) kinase/extracellular signal-regulated kinase (ERK) pathway. Thus,
the neurotrophic actions of these distinct classes of compounds can be
understood from their ability to bind steroid receptor chaperones, thereby
providing a unique receptor-mediated means to activate the ERK pathway. These
studies thereby shed new light on the intrinsic mechanism regulating axonal
elongation. Furthermore, this mechanism may also underlie
calcineurin-independent neuroprotective actions of FK506. We suggest that
components of steroid receptor complexes are novel targets for the design of
neuroregenerative/neuroprotective drugs.
N. Ref:: 98
----------------------------------------------------
[174]
TÍTULO / TITLE: - Donor specific
transfusion in kidney transplantation: effect of different immunosuppressive
protocols on graft outcome.
REVISTA
/ JOURNAL: - Transplant Proc 2001 Aug;33(5):2787-8.
AUTORES
/ AUTHORS: - Barbari A; Stephan A; Masri MA; Joubran N;
Dagher O; Kamel G
INSTITUCIÓN
/ INSTITUTION: - Department ofNephrology and
Transplantation, Rizk Hospital, Beirut, Lebanon.
----------------------------------------------------
[175]
TÍTULO / TITLE: - Sequential protocol
biopsies from renal transplant recipients show an increasing expression of
active TGF beta.
REVISTA
/ JOURNAL: - Transpl Int 2002 Dec;15(12):630-4. Epub
2002 Oct 19.
●●
Enlace al texto completo (gratuito o de pago) 1007/s00147-002-0472-3
AUTORES
/ AUTHORS: - Jain S; Mohamed MA; Sandford R; Furness
PN; Nicholson ML; Talbot D
INSTITUCIÓN
/ INSTITUTION: - University Department of Surgery,
Leicester General Hospital, Gwendolen Road, Leicester, LE5 4PW, UK. sj34@le.ac.uk
RESUMEN
/ SUMMARY: - Chronic allograft nephropathy (CAN) is a
major cause of graft loss after renal transplantation. Implicated in the
pathogenesis of this complication is overproduction of the cytokine
transforming growth factor beta (TGF beta). In this study we measured changes
in CAN’s expression in stable patients early after transplantation, and studied
links with established risk factors for CAN, such as delayed graft function,
acute rejection, and cyclosporine exposure. We took biopsies from 40 renal
allografts at time of transplantation (pre-perfusion), and then, using
ultrasound guidance, at 1 week and 6 months after transplantation. An
immunofluorescence technique was used to stain sections for active TGF beta.
These were then assessed by semi-quantitative scanning laser confocal
microscopy. There was very little variation in active TGF-beta expression among
patients in their pre-perfusion biopsies. Expression had increased by 1 week
and then very significantly by 6 months ( P<0.0001). Patients who suffered
delayed graft function had increased TGF-beta expression at both time points.
There was no difference regarding donor type, acute rejection, and
immunosuppressive drug (cyclosporine or tacrolimus). There was no correlation
between the amount of TGF-beta expression at any time-point and isotope
glomerular filtration rate (GFR) at 12 months. This study demonstrated that in
a group of stable renal allograft recipients, TGF-beta expression in the kidney
increased after transplantation. As the study used protocol biopsies, this
increase is unlikely to be due to acute events, and probably represents a genuine
increase.
----------------------------------------------------
[176]
TÍTULO / TITLE: - Overview of clinical
trials with new agents.
REVISTA
/ JOURNAL: - Transplant Proc 2001 May;33(3):2201-3.
AUTORES
/ AUTHORS: - Charpentier B; Hiesse C; Durrbach A; Ammor
M; Von Ey F; Kechrid C; Kriaa F
INSTITUCIÓN
/ INSTITUTION: - Nephrology Department, University Hospital
of Bicetre, Kremlin Bicetre, France. N.
Ref:: 12
----------------------------------------------------
[177]
TÍTULO / TITLE: - Tailoring immunosuppressive
therapy in renal transplantation.
REVISTA
/ JOURNAL: - Transplant Proc 2002 Sep;34(6):2478-9.
AUTORES
/ AUTHORS: - Vathsala A
INSTITUCIÓN
/ INSTITUTION: - Department of Renal Medicine, Singapore
General Hospital, Singapore. N.
Ref:: 13
----------------------------------------------------
[178]
TÍTULO / TITLE: - The macrolide
immunosuppressants in dermatology: mechanisms of action.
REVISTA
/ JOURNAL: - Eur J Dermatol 2002 Nov-Dec;12(6):618-22.
AUTORES
/ AUTHORS: - Marsland AM; Griffiths CE
INSTITUCIÓN
/ INSTITUTION: - Dermatology Centre, University of
Manchester School of Medicine, Hope Hospital, United Kingdom. sacha.marsland@virgin.net
RESUMEN
/ SUMMARY: - Macrolides are xenobiotics, produced by
soil fungi, which have immunosuppressant properties. They will probably
revolutionise the treatment of inflammatory dermatoses. This article outlines
the context and putative mechanisms of action of this novel class of drugs.
Cyclosporin, and the structurally distinct macrolides tacrolimus and
pimecrolimus (an ascomycin derivative), modulate immune-cell function by
inhibiting calcineurin-dependent dephosphorylation-activation of specific
nuclear factors, thus preventing transcription of pro-inflammatory cytokines.
The macrolide rapamycin (sirolimus) acts by abrogating Target of Rapamycin, a
key signalling protein that controls activation of a number of proteins which
direct progression of the cell cycle in response to pro-inflammatory cytokines.
Tacrolimus and pimecrolimus are small enough molecules to penetrate skin and
are available in topical formulations. “Skin-specific” pimecrolimus seems not
to cause systemic immunosuppression when given orally. Neither topical
tacrolimus nor pimecrolimus are capable of producing skin atrophy. Sirolimus
has anti-angiogenic properties that may be beneficial to the treatment of
psoriasis and perhaps skin cancer. N.
Ref:: 27
----------------------------------------------------
[179]
TÍTULO / TITLE: - Pharmacokinetic aspects
of treating infections in the intensive care unit: focus on drug interactions.
REVISTA
/ JOURNAL: - Clin Pharmacokinet 2001;40(11):833-68.
AUTORES
/ AUTHORS: - Pea F; Furlanut M
INSTITUCIÓN
/ INSTITUTION: - Institute of Clinical Pharmacology and
Toxicology, Department of Experimental and Clinical Pathology and Medicine,
Medical School, University of Udine, Italy. federico.pea@med.uniud.it
RESUMEN
/ SUMMARY: - Pharmacokinetic interactions involving
anti-infective drugs may be important in the intensive care unit (ICU).
Although some interactions involve absorption or distribution, the most
clinically relevant interactions during anti-infective treatment involve the
elimination phase. Cytochrome P450 (CYP) 1A2, 2C9, 2C19, 2D6 and 3A4 are the
major isoforms responsible for oxidative metabolism of drugs. Macrolides
(especially troleandomycin and erythromycin versus CYP3A4), fluoroquinolones
(especially enoxacin, ciprofloxacin and norfloxacin versus CYP1A2) and azole
antifungals (especially fluconazole versus CYP2C9 and CYP2C19, and ketoconazole
and itraconazole versus CYP3A4) are all inhibitors of CYP-mediated metabolism
and may therefore be responsible for toxicity of other coadministered drugs by
decreasing their clearance. On the other hand, rifampicin is a nonspecific
inducer of CYP-mediated metabolism (especially of CYP2C9, CYP2C19 and CYP3A4)
and may therefore cause therapeutic failure of other coadministered drugs by
increasing their clearance. Drugs frequently used in the ICU that are at risk
of clinically relevant pharrmacokinetic interactions with anti-infective agents
include some benzodiazepines (especially midazolam and triazolam),
immunosuppressive agents (cyclosporin, tacrolimus), antiasthmatic agents
(theophylline), opioid analgesics (alfentanil), anticonvulsants (phenytoin,
carbamazepine), calcium antagonists (verapamil, nifedipine, felodipine) and
anticoagulants (warfarin). Some lipophilic anti-infective agents inhibit
(clarithromycin, itraconazole) or induce (rifampicin) the transmembrane
transporter P-glycoprotein, which promotes excretion from renal tubular and
intestinal cells. This results in a decrease or increase, respectively, in the
clearance of P-glycoprotein substrates at the renal level and an increase or
decrease, respectively, of their oral bioavailability at the intestinal level.
Hydrophilic anti-infective agents are often eliminated unchanged by renal
glomerular filtration and tubular secretion, and are therefore involved in
competition for excretion. Beta-lactams are known to compete with other drugs
for renal tubular secretion mediated by the organic anion transport system, but
this is frequently not of major concern, given their wide therapeutic index.
However, there is a risk of nephrotoxicity and neurotoxicity with some
cephalosporins and carbapenems. Therapeutic failure with these hydrophilic
compounds may be due to haemodynamically active coadministered drugs, such as
dopamine, dobutamine and furosemide, which increase their renal clearance by
means of enhanced cardiac output and/or renal blood flow. Therefore,
coadministration of some drugs should be avoided, or at least careful
therapeutic drug monitoring should be performed when available. Monitoring may
be especially helpful when there is some coexisting pathophysiological
condition affecting drug disposition, for example malabsorption or marked
instability of the systemic circulation or of renal or hepatic function. N. Ref:: 397
----------------------------------------------------
[180]
TÍTULO / TITLE: - Plant growth and the
TOR pathway.
REVISTA
/ JOURNAL: - Curr Top Microbiol Immunol
2004;279:97-113.
AUTORES
/ AUTHORS: - Menand B; Meyer C; Robaglia C
INSTITUCIÓN
/ INSTITUTION: - CEA Cadarache DSV DEVM, Laboratoire du
Metabolisme Carbone, UMR 163 CNRS CEA, Univ-Mediterranee UMR 163,
Saint-Paul-lez-Durance, France.
RESUMEN
/ SUMMARY: - In mammalian, insect, and yeast cells, TOR
proteins are essential regulators of cell growth in response to environmental signals
including nutrients, mitogens, and stresses. Although many aspects of the
TOR-dependent signalling pathway are conserved between animals and fungi,
important differences have also been found and are likely to be related to the
ecophysiological adaptations of these organisms. The TOR protein also exists in
plants. This review will first discuss specific aspects of plants concerning
the contribution of cell growth to overall growth, as well as their responses
to nutrient starvation, with emphasis on recent results obtained through
genetic analysis in the model plant Arabidopsis thaliana. This is followed by
the current status of the genetic analysis of the TOR gene in this plant and
the search for potential members of a TOR pathway in the Arabidopsis genome. N. Ref:: 51
----------------------------------------------------
[181]
TÍTULO / TITLE: - Gut failure and
abdominal visceral transplantation.
REVISTA
/ JOURNAL: - Proc Nutr Soc 2003 Aug;62(3):727-37.
●●
Enlace al texto completo (gratuito o de pago) 1079/PNS2003288
AUTORES
/ AUTHORS: - Abu-Elmagd K; Bond G
INSTITUCIÓN
/ INSTITUTION: - Intestinal Rehabilitation and
Transplantation Center, Thomas E. Starzl Transplantation Institute, University of
Pittsburgh School of Medicine, University of Pittsburgh Medical Center,
Pittsburgh, PA 15213, USA. abuelmagdkm@msx.upmc.edu
RESUMEN
/ SUMMARY: - Despite the reported high survival with
total parenteral nutrition (TPN) therapy for patients with intestinal failure,
a considerable number of patients do not escape the potential risks of
TPN-associated complications, including hepatic failure, vanishing of central
venous access and line sepsis. Thus, intestinal, liver-intestinal and
multivisceral transplantation have recently emerged to rescue those who can no
longer be maintained on TPN. Before this development, and for nearly three
decades, small-bowel transplantation was plagued with uncontrolled rejection, graft
v. host disease and fatal infection. These barriers stemmed from the large gut
lymphoid mass and heavy microbial load contained in the intestinal lumen. The
recent improvement in survival after the clinical introduction of tacrolimus
with achievement of full enteric nutritional autonomy qualified the procedure
by the US Health Care Financing Administration as the standard of care for
patients with intestinal and TPN failure. The decision was supported by a
decade of clinical experience with cumulative improvement in patient and graft
survival. In addition, the introduction of new effective immunoprophylactic
agents and novel therapeutic approaches has contributed to a further increase
in the therapeutic advantages of the procedure. The present review article
outlines the current clinical practice of intestinal transplantation and
defines new management strategies with the aim of raising the level of the
procedure to be a better alternative therapy for TPN-dependent patients. N. Ref:: 31
----------------------------------------------------
[182]
TÍTULO / TITLE: - Cyclophilin D as a drug
target.
REVISTA
/ JOURNAL: - Curr Med Chem 2003 Aug;10(16):1485-506.
AUTORES
/ AUTHORS: - Waldmeier PC; Zimmermann K; Qian T;
Tintelnot-Blomley M; Lemasters JJ
INSTITUCIÓN
/ INSTITUTION: - Nervous System Research, Novartis Pharma
Ltd., CH-4002 Basel, Switzerland. peter.waldmeier@pharma.novartis.com
RESUMEN
/ SUMMARY: - The mitochondrial permeability transition
(MPT) plays an important role in damage-induced cell death, and agents
inhibiting the MPT may have a therapeutic potential for treating human
conditions such as ischemia/reperfusion injury, trauma, and neurodegenerative
diseases. The mitochondrial matrix protein, cyclophilin D (CYP D), a member of
a family of highly homologous peptidylprolyl cis-trans isomerases (PPIases),
plays a decisive role in MPT, being an integral constituent of the MPT pore.
Other putative MPT pore proteins include the adenine nucleotide translocator
(ANT) and the voltage-dependent anion channel (VDAC). In an alternative model,
the MPT pore is formed by clusters of misfolded membrane proteins outlining
aqueous channels that are regulated by CYP D and other chaperone-like proteins.
Like cyclophilin A (CYP A) and other cyclophilin family members, CYP D is
targeted by the immunosuppressant cyclosporin A (CsA). CsA is cytoprotective in
many cellular and animal models, but protection may result from either
inhibition of the MPT through an interaction with CYP D or inhibition of
calcineurin-mediated dephosphorylation of BAD through an interaction with CYP
A. The relevance of MPT inhibition by CsA for its cytoprotective effects is
well documented in many cellular models. Mechanisms of action in vivo are more
difficult to define, and accordingly the evidence is as yet less compelling in
in vivo animal models of ischemia/reperfusion injury, trauma and
neurodegenerative diseases. Notwithstanding, CYP D is a drug target of high
interest. Structural considerations suggest feasibility of designing CYP D
ligands without immunosuppressant properties. This is highly desirable, since
they have the potential of being useful therapeutic agents in a variety of
disease states. It might be a tougher challenge to obtain compounds specific
for CYP D vs. other cyclophilins, and/or of small molecular weight, allowing
brain penetration to make them suitable for treating neurodegenerative
diseases. N. Ref:: 204
----------------------------------------------------
[183]
TÍTULO / TITLE: - Infectious
complications in SLE after immunosuppressive therapies.
REVISTA
/ JOURNAL: - Curr Opin Rheumatol 2003 Sep;15(5):528-34.
AUTORES
/ AUTHORS: - Kang I; Park SH
INSTITUCIÓN
/ INSTITUTION: - Section of Rheumatology, Yale University
School of Medicine, New Haven, Connecticut 06520, USA. insoo.kang@yale.edu
RESUMEN
/ SUMMARY: - Immunosuppressive drugs have become the
gold standard for the treatment of major organ involvement in systemic lupus
erythematosus. The use of immunosuppressive therapy in systemic lupus
erythematosus carries significant risks for infection. This article reviews
infectious complications in systemic lupus erythematosus, focusing on effects
of immunosuppressive therapy. Patients with systemic lupus erythematosus appear
to carry an intrinsically increased risk for infection. Recent studies support
this notion further by showing increased risk for serious infections in
patients with systemic lupus erythematosus who had mannose-binding lectin
deficiency associated with homozygous mannose-binding lectin variant alleles.
Patients with systemic lupus erythematosus who were homozygous for
mannose-binding lectin variant alleles had a fourfold increase in the incidence
of infections, requiring hospitalization. In terms of extrinsic risk factors
for infection, use of steroids and cyclophosphamide are the strongest risk
factors. The effect of these drugs on infection is also dose dependent. The
incidence of infectious complications in patients treated with mycophenolate
mofetil, a newly used immunosuppressive drug in systemic lupus erythematosus,
appears less frequent compared with cyclophosphamide. Herpes zoster is still
the most common viral infection in patients with systemic lupus erythematosus
treated with cyclophosphamide and mycophenolate mofetil. Overall data indicate
that patients with systemic lupus erythematosus may have intrinsically
increased risks for infection that are augmented by immunosuppressive therapies.
Cyclophosphamide, in particular in combination with high-dose glucocorticoids,
has the strongest effect in suppressing the immune responses against
microorganisms. Careful monitoring of infectious complications is warranted in
patients with systemic lupus erythematosus receiving immunosuppressive
therapies, in particular those on high-dose glucocorticoids and cytotoxic
drugs. N. Ref:: 87
----------------------------------------------------
[184]
TÍTULO / TITLE: - Teaching old drugs new
tricks: reincarnating immunosuppressants as antifungal drugs.
REVISTA
/ JOURNAL: - Curr Opin Investig Drugs 2003
Feb;4(2):192-9.
AUTORES
/ AUTHORS: - Blankenship JR; Steinbach WJ; Perfect JR;
Heitman J
INSTITUCIÓN
/ INSTITUTION: - Department of Molecular Genetics and Microbiology,
Duke University Medical Center, Research Drive, Durham, NC 27710, USA.
RESUMEN
/ SUMMARY: - Invasive fungal infections are rising
worldwide as the number of immunocompromised patients increases. Unfortunately,
our armamentarium of antifungal drugs is limited. Although current therapies
are effective in treating some of the most prevalent infections, the
development of novel treatments is vital because of emerging drug-resistant
strains and species and because of the toxicity of certain current therapies.
The immunosuppressive drugs CsA (cyclosporin A), FK-506 (tacrolimus) and
rapamycin (sirolimus) exert potent antifungal effects against a variety of
pathogenic fungi. These compounds are all currently in clinical use as
immunosuppressive therapy to treat and prevent rejection of transplanted
organs. Rapamycin is also in clinical trials as an antiproliferative agent for
chemotherapy and invasive cardiology. Recent studies reveal a potent fungicidal
synergism between azoles and the calcineurin inhibitors CsA and FK-506, and
animal studies demonstrate that the CsA-fluconazole synergistic combination has
therapeutic benefit. Less immunosuppressive analogs have been identified with
potential to enhance current therapies, or as monotherapy without deleterious
effects on the immune system. In summary, these highly successful
pharmaceutical agents may find an even broader clinical application in
combating infectious diseases. N.
Ref:: 74
----------------------------------------------------
[185]
TÍTULO / TITLE: - Sirolimus: a new
promising immunosuppressive drug. Towards a rationale for its use in renal
transplantation.
REVISTA
/ JOURNAL: - Nephrol Dial Transplant. Acceso gratuito
al texto completo a partir de los 2 años de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://ndt.oupjournals.org/
●●
Cita: Nephrology Dialysis Transplantation: <> 2001 Jan;16(1):18-20.
AUTORES
/ AUTHORS: - Morelon E; Mamzer-Bruneel MF; Peraldi MN;
Kreis H N. Ref:: 19
----------------------------------------------------
[186]
TÍTULO / TITLE: - Alternariosis after
liver transplantation.
REVISTA
/ JOURNAL: - Transplantation 2001 Dec 15;72(11):1840-3.
AUTORES
/ AUTHORS: - Benito N; Moreno A; Puig J; Rimola A
INSTITUCIÓN
/ INSTITUTION: - Institut Clinic d’ Infeccions i
Inmunologia, IDIBAPS, Hospital Clinic, Universitat de Barcelona, España. nbenito@clinic.ub.es
RESUMEN
/ SUMMARY: - Alternaria is a saprophytic fungus that is
increasingly recognized as a human pathogen, particularly in immunocompromised
hosts, including solid-organ transplant recipients. Although combined surgical
and medical treatment seem to be useful in the management of this infection, an
optimal antifungal therapy remains to be defined. Only four cases of
alternariosis after orthotopic liver transplantation have been reported. We
describe an additional case and review the literature on infections due to
Alternaria in organ transplant recipients, with special emphasis on
treatment. N. Ref:: 20
----------------------------------------------------
[187]
TÍTULO / TITLE: - T-cell depleting
antibodies: new hope for induction of allograft tolerance in bone marrow
transplantation?
REVISTA
/ JOURNAL: - BioDrugs 2003;17(3):147-54.
AUTORES
/ AUTHORS: - Simpson D
INSTITUCIÓN
/ INSTITUTION: - North Shore Hospital, PB 93-503, Takapuna,
Auckland 1309, New Zealand. david.simpson@whl.co.nz
RESUMEN
/ SUMMARY: - Graft versus host disease (GVHD) remains
the main barrier to successful allogeneic bone marrow transplant outcomes.
Depletion of graft T cells is an effective way of reducing the incidence of
acute and chronic GVHD, and a variety of methods have been used to achieve this
depletion. Donor CD8+ T cells seem to be the critical effector cells; GVHD is
reduced when the depletion process eliminates these cells, but not when CD4
cells are targeted alone. However, despite the successful reduction in GVHD,
transplant outcomes are usually inferior with T-cell depleted transplants,
because of increased graft failure, infections and relapse. Alternative
approaches are needed. In vivo T-cell depletion, using antithymocyte globulin
(ATG) as part of the conditioning regimen, seems an attractive option.
Pre-transplant ATG lingers in the bone marrow to deplete engrafting donor T
cells, but also depletes host T cells to prevent graft rejection and allow
de-escalation of the conditioning regimen. It also avoids the need for graft
manipulation with its associated costs, need for expertise and CD34+ cell loss.
The efficacy of pre-transplant horse ATG remains anecdotal but it has been
reported to modestly lower GVHD in single arm studies. Rabbit ATG has been
studied in prospective randomised trials. There is evidence of a dose-response
effect in reducing GVHD; however, there was no improvement in outcome, because
of increased mortality associated with infection. In contrast, pre-transplant
alemtuzumab (campath-1H) or an earlier version of this molecule (campath-1G),
which target CD52+ cells, do appear to be effective in reducing both acute and
chronic GVHD. There is speculation that this is not solely due to the effect of
campath on T cells but that it may also be due to the elimination of host
antigen-presenting cells (APC), which seem to be important in GVHD
pathogenesis. Host APC are more efficient at expressing endogenous and
exogenous host antigens on class I MHC to donor CD8+ cells than donor APC,
which need to cross-prime exogenous antigen. Campath-1G eliminates host
dendritic cells by the time of graft infusion, supporting this as a possible
mechanism of action. Pre-transplant alemtuzumab has not yet been studied in a
prospective randomised study, and this is required to quantify any benefit on
outcome; despite this, published studies do show cause for optimism. N. Ref:: 42
----------------------------------------------------
[188]
TÍTULO / TITLE: - Subcutaneous infection
with Mycobacterium fortuitum after allogeneic bone marrow transplantation.
REVISTA
/ JOURNAL: - Bone Marrow Transplant 2001
Oct;28(7):709-11.
●●
Enlace al texto completo (gratuito o de pago) 1038/sj/bmt/1703211
AUTORES
/ AUTHORS: - Okano A; Shimazaki C; Ochiai N; Hatsuse M;
Takahashi R; Ashihara E; Inaba T; Fujita N; Noda Y; Nakagawa M
INSTITUCIÓN
/ INSTITUTION: - Second Department of Medicine, Kyoto
Prefectural University of Medicine, 465 Kawaramachi-Hirokoji, Kami-gyoku,
Kyoto, 602-8566, Japan.
RESUMEN
/ SUMMARY: - Reports of cases of mycobacterial
infections after SCT are rare. We report a 30-year-old female with a cutaneous
infection of Mycobacterium fortuitum 30 months after allogeneic bone marrow
transplantation for acute lymphoblastic leukemia. The patient was successfully
treated with surgical debridement followed by oral minocycline and
clarithromycin. Mycobacterial infections should be considered in SCT patients
with undiagnosed refractory chronic cutaneous infection, and surgical debridement
is useful for the diagnosis and treatment of such infections. N. Ref:: 7
----------------------------------------------------
[189]
TÍTULO / TITLE: - Immune activation is
required for the induction of liver allograft tolerance: implications for immunosuppressive
therapy.
REVISTA
/ JOURNAL: - Liver Transpl 2001 Mar;7(3):161-72.
●●
Enlace al texto completo (gratuito o de pago) 1053/jlts.2001.22321
AUTORES
/ AUTHORS: - Bishop GA; McCaughan GW
INSTITUCIÓN
/ INSTITUTION: - A.W. Morrow Gastroenterology and Liver
Laboratory, Centenary Institute, Royal Prince Alfred Hospital, Camperdown,
Sydney, Australia.
RESUMEN
/ SUMMARY: - Liver transplants in many animal models
are unusual because often they are not rejected even when transplanted across
complete major histocompatibility complex barriers without immunosuppression.
Their paradoxical behavior is even more obvious when the immune mechanism of
acceptance is examined. Instead of acceptance resulting from a lack of immune
response to the graft, the opposite occurs, and there is an unusual extensive
increase in immune activation in acceptance compared with rejection. This
abnormal extensive immune activation is driven by donor leukocytes transferred
with the liver and results in death of the recipient cells that would normally
reject the transplant. Some forms of immunosuppression inhibit this
activation-associated liver transplant tolerance. The significance of these
findings and possible means to design future treatment protocols for clinical
transplantation that optimize management of liver transplant recipients are
discussed. N. Ref:: 97
----------------------------------------------------
[190]
TÍTULO / TITLE: - Evolution of
immunosuppression and continued importance of acute rejection in renal
transplantation.
REVISTA
/ JOURNAL: - Am J Kidney Dis 2001 Dec;38(6 Suppl
6):S2-9.
AUTORES
/ AUTHORS: - Chan L; Gaston R; Hariharan S
INSTITUCIÓN
/ INSTITUTION: - Department of Renal Medicine, University
of Colorado Health Sciences Center, Denver, CO 80262, USA. Larry.Chan@uchsc.edu
RESUMEN
/ SUMMARY: - As steady improvement in short-term kidney
graft survival and long-term outcomes prolongs the lives of transplant
patients, responsibility for their care is shifting away from transplant
specialists and into the hands of community nephrologists. Therefore, community
nephrologists need to have a deeper understanding of immunosuppressive
therapies than ever before. Pharmacologic immunosuppression has been
continuously evolving over the past two decades. Azathioprine was introduced in
the early 1960s. Introduction of cyclosporine (CsA) in 1983 revolutionized
short-term outcomes after renal transplantation. The first monoclonal antibody
immunosuppressant, OKT3, was introduced in 1986. The 1990s saw the introduction
of a number of important new agents, including mycophenolate mofetil (MMF),
tacrolimus, and a microemulsion CsA, as well as two new monoclonal antibodies.
Combinations of these new agents, along with improving clinical care, have
produced 1-year patient survival approaching 100% and graft survival exceeding
90%. The newest class of agents, the first of which is sirolimus, is called
target of rapamycin (TOR) inhibitors and is used with CsA for maintenance
therapy. Immunosuppressive drug therapy after kidney transplantation continues
to evolve. There is a variety of pharmacologic combinations from which to
choose, based on immunologic risk and side effect profiles. As new regimens are
developed, ongoing communications between the transplant center and community
nephrologists will be required to implement therapeutic changes and optimize
patient care successfully. N.
Ref:: 59
----------------------------------------------------
[191]
TÍTULO / TITLE: - Decreasing side effects
of Neoral through three-times-a-day protocol in Chinese renal transplant
patients.
REVISTA
/ JOURNAL: - Transplant Proc 2001
Nov-Dec;33(7-8):3156-7.
AUTORES
/ AUTHORS: - Chen ZS; Zeng FJ; Lin ZB; Chen ZK; Sha B;
Wen ZX; Ming CS; Zhang WJ; Xia SS
INSTITUCIÓN
/ INSTITUTION: - Institute of Organ Transplantation, Tongji
Hospital, Tongji Medical College, Huazhong University of Science and
Technology, Wuhan, China.
----------------------------------------------------
[192]
TÍTULO / TITLE: - Influence of
cyclosporin, tacrolimus and rapamycin on renal function and arterial
hypertension after renal transplantation.
REVISTA
/ JOURNAL: - Nephrol Dial Transplant. Acceso gratuito
al texto completo a partir de los 2 años de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://ndt.oupjournals.org/
●●
Cita: Nephrology Dialysis Transplantation: <> 2001;16 Suppl 1:121-4.
AUTORES
/ AUTHORS: - Morales JM; Andres A; Rengel M; Rodicio JL
INSTITUCIÓN
/ INSTITUTION: - Renal Transplant Unit, Nephrology
Department, Hospital 12 de Octubre, Madrid, España.
RESUMEN
/ SUMMARY: - Cyclosporin and tacrolimus have improved
survival figures in organ transplantation. However, both drugs are potentially
nephrotoxic. The immunosuppressive and nephrotoxic effects of both drugs appear
to depend on the inhibition of calcineurin. Cyclosporin and tacrolimus cause
acute (functional changes) and chronic nephrotoxicity (structural lesions in
the kidney). These last important lesions include arteriolar hyalinosis,
stripped interstitial fibrosis and tubular atrophy. It is possible that
repeated episodes of renal ischaemia contribute to the development of chronic
nephrotoxicity and then chronic allograft nephropathy. Cyclosporin and
tacrolimus also induce arterial hypertension. Therefore, the beneficial effects
of immunosuppression have been limited due to nephrotoxicity and arterial
hypertension. Rapamycin, a novel immunosuppressive agent, that does not inhibit
calcineurin, provides immunosuppression without nephrotoxicity. In fact, in the
trials performed in Europe, sirolimus-treated immunosuppression patients
exhibited a much better renal function than cyclosporin-treated patients.
However, sirolimus can potentiate the nephrotoxic effect of cyclosporin.
Therefore, when cyclosporin and sirolimus are used in combination, a reduction
of the cyclosporin dose is desirable. N.
Ref:: 28
----------------------------------------------------
[193]
TÍTULO / TITLE: - Sirolimus-based
immunosuppressive [correction of immunosuppresive] protocol for calcineurin
sparing in liver transplantation.
REVISTA
/ JOURNAL: - Transplant Proc 2002 Aug;34(5):1522-3.
AUTORES
/ AUTHORS: - Heffron TG; Smallwood GA; Davis L;
Martinez E; Stieber AC
INSTITUCIÓN
/ INSTITUTION: - Department of Surgery, Emory University
School of Medicine, Atlanta, GA 30322, USA.
----------------------------------------------------
[194]
TÍTULO / TITLE: - Sirolimus and islet
transplants.
REVISTA
/ JOURNAL: - Transplant Proc 2003 May;35(3
Suppl):187S-190S.
AUTORES
/ AUTHORS: - Hering BJ; Wijkstrom M
INSTITUCIÓN
/ INSTITUTION: - Diabetes Institute for Immunology and
Transplantation, Department of Surgery, University of Minnesota, Minneapolis,
Minnesota, USA. N.
Ref:: 36
----------------------------------------------------
[195]
TÍTULO / TITLE: - Successful treatment of
refractory Langerhans cell histiocytosis with unrelated cord blood
transplantation.
REVISTA
/ JOURNAL: - J Pediatr Hematol Oncol 2001
Dec;23(9):629-32.
AUTORES
/ AUTHORS: - Nagarajan R; Neglia J; Ramsay N; Baker KS
INSTITUCIÓN
/ INSTITUTION: - Department of Pediatrics, Division of
Hematology/Oncology/Blood and Marrow Transplant, University of Minnesota,
Minneapolis, USA. nagar003@tc.umn.edu
RESUMEN
/ SUMMARY: - A 2-month-old girl presented for treatment
with a diffuse rash, interstitial pneumonia, otorrhea, and lymphadenopathy.
Skin biopsy confirmed Langerhans cell histocytosis by electron microscopy.
After receiving multiple courses of chemotherapy, only marginal improvement was
achieved, with progressive marrow and liver involvement. The decision was made
to pursue a human leukocyte antigen-identical unrelated cord blood
transplantation. Two years after transplant, the bone marrow was clear of
Langerhans cell histocytosis and 100% donor engraftment. The poor prognosis of
patients with an inadequate response to therapy and the presence of organ
dysfunction (marrow and liver) substantiated the decision to pursue an
unrelated cord blood transplantation. N.
Ref:: 20
----------------------------------------------------
[196]
TÍTULO / TITLE: - mTOR signaling to
translation.
REVISTA
/ JOURNAL: - Curr Top Microbiol Immunol
2004;279:169-97.
AUTORES
/ AUTHORS: - Gingras AC; Raught B; Sonenberg N
INSTITUCIÓN
/ INSTITUTION: - Department of Biochemistry, McGill Cancer
Centre, McGill University, 3655 Promenade Sir-William-Osler, Montreal, Quebec,
H3G 1Y6, Canada.
RESUMEN
/ SUMMARY: - Over the past few years, the target of
rapamycin (TOR) pathway has been implicated in the control of translation, both
in yeast and in higher eukaryotes. In this review, we provide an overview of
translation in eukaryotes, and discuss the mechanisms and advantages of the
regulation of translation. We then describe how the TOR pathway can modulate
translation in yeast and in mammals, through the modulation of the
phosphorylation of key translation components, and the regulation of the abundance
of ribosomes and translation factors. N.
Ref:: 117
----------------------------------------------------
[197]
TÍTULO / TITLE: - Immunosuppression
protocols for HLA identical renal transplant recipients.
REVISTA
/ JOURNAL: - Transplant Proc 2003 May;35(3):1074-5.
AUTORES
/ AUTHORS: - Keitel E; Santos AF; Alves MA; Neto JP;
Schaefer PG; Bittar AE; Goldani JC; Pozza R; Bruno RM; See D; Garcia CD; Garcia
VD
INSTITUCIÓN
/ INSTITUTION: - Renal Transplant Unit, Santa Casa
Hospital, Porto Alegre, RS, Brazil. keitel@terra.com.br
----------------------------------------------------
[198]
TÍTULO / TITLE: - Sirolimus in liver
transplantation.
REVISTA
/ JOURNAL: - Transplant Proc 2003 May;35(3
Suppl):193S-200S.
AUTORES
/ AUTHORS: - Trotter JF
INSTITUCIÓN
/ INSTITUTION: - Division of Gastroenterology/Hepatology,
University of Colorado Health Sciences Center, Boulder, Colorado 80262, USA. James.Trotter@uchsc.edu
RESUMEN
/ SUMMARY: - Since its introduction in renal
transplantation in 1999, sirolimus is being used by an increasing number of
liver transplant centers. Compared to the calcineurin inhibitors, sirolimus
acts through a separate signal transduction pathway and has a myriad of
important biologic effects including: inhibition of lymphocyte proliferation,
inhibition of fibrosis and fibroblast proliferation, and antineoplastic
effects. The clinical side-effect profile of this drug is also different than
calcineurin inhibitors. Most important, sirolimus does not cause glucose
intolerance, hypertension, or renal insufficiency. As a result, this drug
offers significant potential advantages over conventional immunosuppressive
agents. However, sirolimus may cause hyperlipidemia and has also been
associated with hepatic artery thrombosis in liver transplant recipients. This
review will summarize the published data on sirolimus in liver transplantation,
focusing on the potential advantages and disadvantage of the use of this drug
in liver transplant recipients. Finally, the potential benefits of antifibrosis
and antineoplastic effects of sirolimus in liver transplant recipients will be
discussed. N. Ref:: 29
----------------------------------------------------
[199]
TÍTULO / TITLE: - Focal segmental
glomerulosclerosis: pathogenesis and treatment.
REVISTA
/ JOURNAL: - Curr Opin Pediatr 2003 Apr;15(2):171-80.
AUTORES
/ AUTHORS: - Benchimol C
INSTITUCIÓN
/ INSTITUTION: - Department of Pediatrics, Mount Sinai
School of Medicine, NewYork, NewYork 10029, USA. Corinne.benchimol@mssn.edu N. Ref:: 144
----------------------------------------------------
[200]
TÍTULO / TITLE: - The involvement of
mammalian and plant FK506-binding proteins (FKBPs) in development.
REVISTA
/ JOURNAL: - Transgenic Res 2002 Aug;11(4):321-35.
AUTORES
/ AUTHORS: - Breiman A; Camus I
INSTITUCIÓN
/ INSTITUTION: - Department of Plant Science, Tel Aviv
University, Israel. adina@post.tau.ac.il
RESUMEN
/ SUMMARY: - The FK506-binding proteins (FKBPs) are
peptidyl prolyl cis/trans isomerases and the information gathered in the last
10 years reveals their involvement in diverse biological systems affecting the
function and structure of target proteins. Members of the FKBP family were
shown to be growth-regulated and participate in signal transduction. In this
review we have chosen to focus on a few examples of the mammalian and plant
systems in which members of the FKBP family have been demonstrated to affect
the function of proteins or development. The technologies that enable
production of knockout mice, Arabidopsis mutants and overexpression in
transgenic organisms have revealed the contribution of FKBP to development in
higher eukaryotes. It appears that members of the FKBP family have conserved
some of their basic functions in the animal and plant kingdom, whereas other
functions became unique. Studies that will take advantage of the full genome
sequence available for Arabidopsis and the human genome, DNA chip technologies
and the use of transgenic complementation system will contribute to the
elucidation of the molecular mechanism and biological function of FKBPs. N. Ref:: 120
----------------------------------------------------