#12#
Revisiones-Ciencias
Básicas-Fisiología *** Reviews-Basic Sciences-Physiology
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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[1]
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
----------------------------------------------------
[2]
- 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
----------------------------------------------------
[3]
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.
----------------------------------------------------
[4]
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
----------------------------------------------------
[5]
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.
----------------------------------------------------
[6]
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
----------------------------------------------------
[7]
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
----------------------------------------------------
[8]
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
----------------------------------------------------
[9]
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
----------------------------------------------------
[10]
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
----------------------------------------------------
[11]
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.
----------------------------------------------------
[12]
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
----------------------------------------------------
[13]
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
----------------------------------------------------
[14]
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
----------------------------------------------------
[15]
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.
----------------------------------------------------
[16]
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
----------------------------------------------------
[17]
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.
----------------------------------------------------
[18]
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
----------------------------------------------------
[19]
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
----------------------------------------------------
[20]
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.
----------------------------------------------------
[21]
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
----------------------------------------------------
[22]
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
----------------------------------------------------
[23]
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.
----------------------------------------------------
[24]
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
----------------------------------------------------
[25]
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.
----------------------------------------------------
[26]
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
----------------------------------------------------
[27]
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
----------------------------------------------------
[28]
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
----------------------------------------------------
[29]
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
----------------------------------------------------
[30]
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
----------------------------------------------------
[31]
- 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
----------------------------------------------------
[32]
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
----------------------------------------------------
[33]
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
----------------------------------------------------
[34]
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.
----------------------------------------------------
[35]
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
----------------------------------------------------
[36]
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
----------------------------------------------------
[37]
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
----------------------------------------------------
[38]
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
----------------------------------------------------
[39]
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
----------------------------------------------------
[40]
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
----------------------------------------------------
[41]
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
----------------------------------------------------
[42]
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.
----------------------------------------------------
[43]
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
----------------------------------------------------
[44]
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
----------------------------------------------------
[45]
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
----------------------------------------------------
[46]
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
----------------------------------------------------
[47]
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
----------------------------------------------------
[48]
- 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
----------------------------------------------------
[49]
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
----------------------------------------------------
[50]
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
----------------------------------------------------
[51]
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
----------------------------------------------------
[52]
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
----------------------------------------------------
[53]
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
----------------------------------------------------
[54]
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.
----------------------------------------------------
[55]
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
----------------------------------------------------
[56]
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
----------------------------------------------------
[57]
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
----------------------------------------------------
[58]
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
----------------------------------------------------
[59]
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.
----------------------------------------------------
[60]
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.
----------------------------------------------------
[61]
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
----------------------------------------------------
[62]
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
----------------------------------------------------
[63]
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
----------------------------------------------------
[64]
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
----------------------------------------------------
[65]
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
----------------------------------------------------
[66]
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
----------------------------------------------------
[67]
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
----------------------------------------------------
[68]
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
----------------------------------------------------
[69]
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
----------------------------------------------------
[70]
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
----------------------------------------------------
[71]
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
----------------------------------------------------
[72]
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
----------------------------------------------------
[73]
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
----------------------------------------------------
[74]
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.
----------------------------------------------------
[75]
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
----------------------------------------------------
[76]
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.
----------------------------------------------------
[77]
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
----------------------------------------------------
[78]
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
----------------------------------------------------
[79]
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
----------------------------------------------------
[80]
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.
----------------------------------------------------
[81]
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
----------------------------------------------------
[82]
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
----------------------------------------------------
[83]
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
----------------------------------------------------
[84]
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
----------------------------------------------------
[85]
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
----------------------------------------------------
[86]
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.
----------------------------------------------------
[87]
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
----------------------------------------------------
[88]
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
----------------------------------------------------
[89]
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
----------------------------------------------------
[90]
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.
----------------------------------------------------
[91]
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
----------------------------------------------------
[92]
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
----------------------------------------------------
[93]
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
----------------------------------------------------
[94]
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
----------------------------------------------------
[95]
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
----------------------------------------------------
[96]
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
----------------------------------------------------
[97]
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
----------------------------------------------------
[98]
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
----------------------------------------------------
[99]
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
----------------------------------------------------
[100]
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
----------------------------------------------------
[101]
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
----------------------------------------------------
[102]
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
----------------------------------------------------
[103]
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
----------------------------------------------------
[104]
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
----------------------------------------------------
[105]
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
----------------------------------------------------
[106]
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
----------------------------------------------------
[107]
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
----------------------------------------------------
[108]
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.
----------------------------------------------------
[109]
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
----------------------------------------------------
[110]
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
----------------------------------------------------
[111]
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
----------------------------------------------------
[112]
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
----------------------------------------------------
[113]
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
----------------------------------------------------
[114]
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
----------------------------------------------------
[115]
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.
----------------------------------------------------
[116]
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.
----------------------------------------------------
[117]
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
----------------------------------------------------
[118]
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
----------------------------------------------------
[119]
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
----------------------------------------------------
[120]
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
----------------------------------------------------
[121]
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
----------------------------------------------------
[122]
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
----------------------------------------------------
[123]
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
----------------------------------------------------
[124]
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
----------------------------------------------------
[125]
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
----------------------------------------------------
[126]
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.
----------------------------------------------------
[127]
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
----------------------------------------------------
[128]
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.
----------------------------------------------------
[129]
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
----------------------------------------------------
[130]
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
----------------------------------------------------
[131]
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
----------------------------------------------------
[132]
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
----------------------------------------------------
[133]
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
----------------------------------------------------
[134]
TÍTULO / TITLE: - The immune-suppressive
effects of pain.
REVISTA
/ JOURNAL: - Adv Exp Med Biol 2003;521:117-25.
AUTORES
/ AUTHORS: - Page GG
INSTITUCIÓN
/ INSTITUTION: - Johns Hopkins University School of
Nursing, Baltimore, Maryland, USA. N.
Ref:: 56
----------------------------------------------------
[135]
TÍTULO / TITLE: - Mycophenolate mofetil:
suggested guidelines for use in kidney transplantation.
REVISTA
/ JOURNAL: - BioDrugs 2001;15(1):37-53.
AUTORES
/ AUTHORS: - Behrend M
INSTITUCIÓN
/ INSTITUTION: - Abteilung fur Viszeral- und Transplantationschirurgie,
Medizinische Hochschule Hannover, Hannover, Germany. Behrend.Matthias@MH-Hannover.de
RESUMEN
/ SUMMARY: - Mycophenolate mofetil (MMF) is an
immunosuppressive drug designed to inhibit inosine monophosphate dehydrogenase
(IMPDH). IMPDH is a key enzyme in the de novo purine synthesis of lymphocytes.
It is crucially important for proliferative responses of human T and B
lymphocytes. The inhibition of IMPDH thus leads to selective lymphocyte suppression.
After successful use in various in vitro and animal models, MMF was brought to
clinical trial in patients undergoing transplantation. The drug is rapidly and
completely absorbed following oral administration. Pilot studies of
administration with cyclosporin and corticosteroids suggested a significant
reduction in the incidence of organ rejection at dosages of 1 to 3 g/day. As a
result of these studies, 3 pivotal randomised double-blind multicentre trials,
involving nearly 1500 patients, were designed to investigate the effects of
addition of MMF to different standard immunosuppressive protocols on the
prevention of acute renal allograft rejection. After 6 months, the rates of
biopsy-proven rejection were significantly reduced in patients receiving MMF.
In combination with cyclosporin and corticosteroids, the adverse effect profile
resembled that of azathioprine. Most adverse effects were associated with the
gastrointestinal tract, the blood system and opportunistic infections. MMF
offers improved immunosuppressive therapy following renal and probably other
solid organ transplantation. MMF has been licensed since 1995 for the
prevention of acute renal allograft rejection in most countries. It has been
used in different combinations of immunosuppressive drugs and in various
dosages and regimens. N.
Ref:: 124
----------------------------------------------------
[136]
TÍTULO / TITLE: - Treatment with
immunotoxin.
REVISTA
/ JOURNAL: - Philos Trans R Soc Lond B Biol Sci. 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.pubs.royalsoc.ac.uk/
●●
Cita: Philos Trans R Soc Lond B Biol Sci: <> 2001 May 29;356(1409):681-9.
AUTORES
/ AUTHORS: - Knechtle SJ
INSTITUCIÓN
/ INSTITUTION: - Department of Surgery, Division of Organ
Transplantation, 600 Highland Avenue, University of Wisconsin Medical School,
Madison,WI 53792-7375, USA. stuart@tx.surgery.wisc.edu
RESUMEN
/ SUMMARY: - T-cell depletion prior to or beginning at
the time of transplantation has been shown to be a valuable adjunct to the
induction of immunological unresponsiveness. Both total lymphoid irradiation
and anti-lymphocyte globulin have been used for this purpose in experimental
models of transplantation as well as in human organ transplant recipients.
However, these methods of T-cell depletion are limited in their ability to
deplete T cells selectively due to non-specific targeting and limited efficacy.
A new anti-CD3 immunotoxin has been developed with a far more potent ability to
deplete T cells selectively as measured by flow cytometry analysis of
peripheral blood T lymphocytes as well as lymph node lymphocytes. This
immunotoxin is well tolerated by rhesus monkeys when administered in vivo. When
administered as a single immunosuppressive agent pretransplant, it
substantially promotes allograft survival, inducing tolerance in at least
one-third of recipients as measured by subsequent acceptance of donor skin
grafts and rejection of third-party skin grafts. When administered on the day
of transplant in combination with steroid pretreatment and a brief course of
deoxyspergualin or mycophenolate mofetil (4 to 14 days), long-term
unresponsiveness is also produced and in a more reliable manner than using
immunotoxin alone. A new immunotoxin directed at the human CD3epsilon has been
developed with excellent potency in T-cell killing and lacking the Fc portion
of the CD3 antibody. This construct may be useful for T-cell depletion in
humans and has a potential application in tolerance induction in human organ
transplantation. Lessons learned from anti-CD3 immunotoxin in the non-human
primate model to date include (i) profound (2-3 log) depletion of T-cells can
be accomplished safely without inducing lymphoma or infection, (ii) such
depletion is a useful adjunct for tolerance induction to allogeneic organ
transplants, and (iii) tolerance to both allogeneic renal transplants and
xenogeneic islet transplants has been accomplished using such strategies to
date in non-human primates and in pigs. Immunotoxin may be useful for the
induction of chimerism using strategies that include donor bone marrow
infusion. Successful strategies for tolerance induction have also been
developed using immunotoxin without the adjunct of donor bone marrow or stem
cell infusion. Clinical application of immunotoxin will use a newly engineered
construct with the potential for causing cytokine release, less susceptibility
to neutralization by anti-diphtheria antibody and not dependent on chemical
conjugation of an antibody and toxin. The usefulness of immunotoxin is directly
related to its tremendous potency for depleting T cells. Based on results in
nonhuman primates, it is anticipated that it will become a useful agent in
tolerance induction in humans. N.
Ref:: 63
----------------------------------------------------
[137]
TÍTULO / TITLE: - Atopic diseases of
childhood.
REVISTA
/ JOURNAL: - Curr Opin Pediatr 2001 Oct;13(5):487-95.
AUTORES
/ AUTHORS: - Turvey SE
INSTITUCIÓN
/ INSTITUTION: - Division of Immunology, Children’s
Hospital, Boston, Massachusetts 02115, USA. stuart.turvey@tch.harvard.edu N. Ref:: 102
----------------------------------------------------
[138]
TÍTULO / TITLE: - Single-agent
immunosuppression after liver transplantation: what is possible?
REVISTA
/ JOURNAL: - Drugs 2002;62(11):1587-97.
AUTORES
/ AUTHORS: - Raimondo ML; Burroughs AK
INSTITUCIÓN
/ INSTITUTION: - Liver Transplantation and Hepato-Biliary
Medicine, Royal Free Hospital, Hampstead, London, UK.
RESUMEN
/ SUMMARY: - Orthotopic liver transplantation is a life
saving and life enhancing procedure. The development of immunosuppressive drugs
has contributed to the high rate of success in terms of both patient and graft
survival. However, the considerable adverse effects of these therapies are
affecting long-term outcomes of transplant recipients. Complications related to
immunosuppression are responsible for the majority of deaths in patients
surviving more than 1 year. Therefore, the search for an optimal
immunosuppressive regimen has become of paramount importance. The liver has
proved to be an ‘immunologically privileged’ organ, capable in several animal
models to be accepted as an allograft without any intervention on the immune
system of the recipient. In some human liver allografts acceptance of the new
organ is recognised after withdrawal of immunosuppressants, but prior
identification of such individuals is not yet possible, thus negating this
management option. Graft-recipient interaction is peculiar in liver
transplantation: acute cellular rejection does not always need to be treated,
and if it is not severe, appears to be associated with a better survival of
both patient and graft. In the last decade there has been an evolution of
immunosuppressive protocols, driven by empirical observation and a deeper
understanding of immunological events after transplant. However, most
modifications have been made because of the necessity to reduce long-term drug
related morbidity and mortality. Withdrawal of corticosteroids has proven to be
safely achievable in most patients, with no deleterious effects on patient or
graft survival but with a great benefit in terms of reduction of incidence of
metabolic and cardiovascular complications. Long-term ‘steroid-free’ regimens
are therefore now widely used. Patients with stable graft function can be
easily maintained using a single drug usually after 6 or 12 months and usually
with a calcineurin inhibitor. The more evolved step of using monotherapy ab
initio has also proven to be effective in a few studies and needs to be
explored further. In the future new strategies will be designed to help the
development of tolerance of the allograft, selectively stimulating instead of
suppressing the immune reaction of the recipient. N. Ref:: 51
----------------------------------------------------
[139]
TÍTULO / TITLE: - Chronic urticaria:
mechanisms and treatment.
REVISTA
/ JOURNAL: - Allergy Asthma Proc 2001
Mar-Apr;22(2):97-100.
AUTORES
/ AUTHORS: - Fox RW
INSTITUCIÓN
/ INSTITUTION: - Division of Allergy and Immunology,
Department of Internal Medicine, University of South Florida Health Sciences
Center, 13000 Bruce B. Downs Blvd., VAR 111D, Tampa, FL 63312, USA.
RESUMEN
/ SUMMARY: - Chronic urticaria (CU) is a vexing
clinical syndrome. The clinician is challenged by the patient’s symptoms. The
experienced physician can evaluate the CU patient and prescribe effective
treatment. The following review emphasizes the autoimmune mechanisms of CU.
Despite this new insight into the pathogenesis of CU, many cases are still
categorized as idiopathic. CU patients are a heterogenous group of patients who
require an individualized approach to evaluation and management. N. Ref:: 20
----------------------------------------------------
[140]
TÍTULO / TITLE: - Induction of
donor-specific tolerance in rat hind-limb allografts under antilymphocyte serum
and cyclosporine A protocol.
REVISTA
/ JOURNAL: - J Hand Surg [Am] 2002 Nov;27(6):1095-103.
●●
Enlace al texto completo (gratuito o de pago) 1053/jhsu.2002.36524
AUTORES
/ AUTHORS: - Siemionow M; Oke R; Ozer K; Izycki D;
Prajapati R
INSTITUCIÓN
/ INSTITUTION: - Department of Plastic Surgery,
Microsurgery Research, The Cleveland Clinic Foundation, Cleveland, OH 44195,
USA.
RESUMEN
/ SUMMARY: - Composite tissue allograft (CTA)
transplantation became a clinical reality despite major side effects associated
with the administration of chronic immunosuppression. Development of new
treatment modalities eliminating life-long immunosuppression is essential for
the future of CTA transplantation. In this study, combined use of cyclosporine
A (CsA) and antilymphocyte serum (ALS) was tested for the potential to induce
tolerance in the rat hind-limb allograft recipients across a major
histocompatibility (MHC) barrier (Lewis-Brown-Norway [LBN, RT1(l+n)] to Lewis
[LEW, RT1(l)] rats). Thirty transplantations were performed in 5 experimental
groups. Animals received CsA and ALS 12 hours before surgery for 21 days
thereafter. Although the allograft controls rejected their limbs at day 7
combined treatment of CsA and ALS resulted in indefinite survival (over 420 d)
in all allograft recipients. Long-term survivors showed 35% to 42% of
donor-specific chimerism in the peripheral blood. Clinical tolerance was
confirmed by acceptance of the donor-specific skin grafts and immunocompetence
was confirmed by rejection of the third-party grafts. Mixed lymphocyte reaction
revealed suppressed response against donor-type antigens and increased response
to third-party antigens. Donor-specific tolerance across MHC barrier was
induced in CTA allografts under 21 days protocol of ALS/CsA.
----------------------------------------------------
[141]
TÍTULO / TITLE: - Therapeutic drug
monitoring of immunosuppressive drugs in kidney transplantation.
REVISTA
/ JOURNAL: - Curr Opin Nephrol Hypertens 2002
Nov;11(6):657-63.
●●
Enlace al texto completo (gratuito o de pago) 1097/01.mnh.0000040053.33359.26
AUTORES
/ AUTHORS: - Holt DW
INSTITUCIÓN
/ INSTITUTION: - Analytical Unit, St George’s Hospital
Medical School, London, UK. d.holt@sghms.ac.uk
RESUMEN
/ SUMMARY: - PURPOSE OF REVIEW: Drug monitoring has
become an accepted adjunct to optimizing therapy with immunosuppressive drugs.
This review assesses publications that relate to the analytical techniques used
to measure cyclosporin, tacrolimus, mycophenolic acid, sirolimus and
everolimus, as well as the clinical data obtained for these drugs. For all of
these drugs there has been a substantial and continuing investment in assessing
the clinical value of drug monitoring. RECENT FINDINGS: Fundamental
controversies still persist regarding which time point to use for monitoring.
The most significant single development has been the move towards using a timed
blood sample 2 h after drug administration (C2) to monitor cyclosporin therapy
with the Neoral formulation. The favourable clinical results obtained with this
approach have had an impact on reevaluating monitoring data for some of the
other drugs. The newest drugs to reach clinical evaluation, sirolimus and
everolimus, have been studied in the context of concentration-controlled dosing
and there is a good rationale for their measurement. There have also been
developments in the analytical techniques used, mostly to improve the
selectivity of the assays or to adapt them to new monitoring strategies.
SUMMARY: Interpretation of drug concentration data is becoming ever more
complex in this field as the number of potential drug combinations expands. The
relatively narrow therapeutic index of these agents and the ever-present risk of
clinically significant pharmacokinetic drug interactions makes drug monitoring
an important aspect of their prescription.
N. Ref:: 77
----------------------------------------------------
[142]
TÍTULO / TITLE: - Sirolimus (Rapamune) in
renal transplantation.
REVISTA
/ JOURNAL: - Curr Opin Nephrol Hypertens 2002
Nov;11(6):603-7.
●●
Enlace al texto completo (gratuito o de pago) 1097/01.mnh.0000040045.55337.97
AUTORES
/ AUTHORS: - Johnson RW
INSTITUCIÓN
/ INSTITUTION: - Manchester Postgraduate Health Sciences
Centre, Manchester Royal Infirmary, Manchester.
RESUMEN
/ SUMMARY: - There has been a necessary change in
attitude to transplantation; there is much less concern with short-term outcome
and more concern with long-term kidney function, overall health and quality of
life. Nephrotoxicity is an invariable consequence of long-term treatment with
calcineurin antagonists and it is one of the most underestimated causes of late
graft loss; it has been reported as a serious threat to both patient and graft
survival following heart, liver and bone marrow transplantation. Sirolimus has
been shown in many recent studies to be of great value in allowing patients to
be weaned from cyclosporine with excellent patient and graft survival at 24
months a significant improvement in renal function with resolution of hirsutism
and gum hyperplasia. Patients maintained on the combined regime of cyclosporine
and sirolimus had significantly higher blood pressure, much more cyclosporine
nephrotoxicity and hyperuricaemia at 12 months. The experimental studies have
found cyclosporine and sirolimus potentiate with each other’s good and adverse
effects. Cyclosporine therefore augments hyperlipidaemia caused by sirolimus,
and sirolimus augments nephrotoxicity caused by cyclosporine. The results of
these studies indicate that sirolimus is a suitable replacement for
cyclosporine or tacrolimus for long-term maintenance therapy. By contrast the
use of sirolimus in combination with cyclosporine results in potentiation of
side effects. The principal disadvantages being increased cyclosporine
associated nephrotoxicity and sirolimus associated hyperlipidaemia N. Ref:: 32
----------------------------------------------------
[143]
TÍTULO / TITLE: - Autoimmune hepatitis
after liver transplantation and other lessons of self-intolerance.
REVISTA
/ JOURNAL: - Liver Transpl 2002 Jun;8(6):505-13.
●●
Enlace al texto completo (gratuito o de pago) 1053/jlts.2002.33485
AUTORES
/ AUTHORS: - Czaja AJ
INSTITUCIÓN
/ INSTITUTION: - Division of Gastroenterology and
Hepatology, Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA. czaja.albert@mayo.edu
RESUMEN
/ SUMMARY: - Autoimmune hepatitis has been described as
recurrent or de novo disease after transplantation. The legitimacy of these
diagnoses and the bases for their occurrence are unknown. To better understand
these aspects of allograft dysfunction, the purported pathogenic mechanisms of
classical autoimmune hepatitis were reviewed and extrapolated to recurrent and
de novo disease after transplantation. Loss of self-tolerance may relate to
defects in the negative selection of autoreactive immunocytes and the clonal
expansion of promiscuous lymphocytes that are cross-reactive to homologous
antigens (molecular mimicry). Repopulation of the allograft with recipient
antigen-presenting cells and the presence of primed promiscuous cytotoxic T
cells within the recipient are likely factors for recurrent disease. Targets
may be the same peptides that triggered the original disease, donor-derived
class II antigens of the major histocompatibility complex, or homologous
antigens associated with unidentified hepatotrophic viruses. De novo disease is
probably due to similar mechanisms, but its predilection for children suggests
that thymic dysfunction associated with cyclosporine treatment may be a factor.
Corticosteroid therapy is effective in each condition. In conclusion, recurrent
and de novo autoimmune hepatitis after transplantation are examples of
self-intolerance. The mechanisms that perturb immunologic homeostasis in this
human model of the classical disease must be studied more rigorously. N. Ref:: 92
----------------------------------------------------
[144]
TÍTULO / TITLE: - Immunosuppressive
effect of pregnancy on autoimmune hepatitis: a case report and review of
literature.
REVISTA
/ JOURNAL: - Eur J Obstet Gynecol Reprod Biol 2002 Feb
10;101(1):91-2.
AUTORES
/ AUTHORS: - Malhotra B; Malhotra N; Deka D; Takkar D
INSTITUCIÓN
/ INSTITUTION: - Department of Obstetrics and Gynecology,
All India Institute of Medical Sciences, New Delhi, India. bhawnams@hotmail.com
RESUMEN
/ SUMMARY: - We report a case of autoimmune hepatitis
with suppressed disease activity during pregnancy and relapse in puerperium. This
is only the second report of such pregnancy-induced remission. N. Ref:: 7
----------------------------------------------------
[145]
TÍTULO / TITLE: - Bone marrow
transfusions in cadaver renal allografts: pilot trials with concurrent
controls.
REVISTA
/ JOURNAL: - Clin Transplant 2002 Oct;16(5):317-24.
AUTORES
/ AUTHORS: - Light J; Salomon DR; Diethelm AG;
Alexander JW; Hunsicker L; Thistlethwaite R; Reinsmoen N; Stablein DM
INSTITUCIÓN
/ INSTITUTION: - Transplant Services, Washington Hospital
Center, Washington, DC 20010, USA.jimmy.a.light@medstar.net
RESUMEN
/ SUMMARY: - BACKGROUND: The safety and immune
tolerance potential of donor marrow infusion with cadaveric source renal
transplants was evaluated in a series of non-randomized multicenter pilot
trials by the NIH Cooperative Clinical Trials in Transplantation (CCTT) Group.
PATIENTS AND METHODS: Three strategies were tested: (1) immunosuppression with
cyclosporin, azathioprine and prednisone with a single post-transplant day 1
infusion of 5 x 107 viable cells/kg, (2) OKT3 induction with triple drug
therapy and marrow transfusion on day 1, or (3) same therapy as (2) but with an
additional marrow transfusion on day 10-12. RESULTS: Thirty-eight marrow
recipients and 35 contemporaneous controls were entered with a mean follow-up
of over 5 yr. Graft survival was initially better in the marrow recipients than
the controls but was similar after 5 yr. Microchimerism rates were similar for
the marrow infusion and control groups throughout the follow-up period,
regardless of the immunosuppression strategies. DISCUSSION: Bone marrow
infusions were well tolerated by a group of cadaver renal allograft recipients.
There were no complications from the infusion(s), no episodes of graft-vs.-host
disease (GVHD) and no increase in infections or other complications. There was
a trend toward early improved graft survival in marrow recipients. Decreased
rejection rates were observed in black recipients. N. Ref:: 36
----------------------------------------------------
[146]
TÍTULO / TITLE: - An induction versus
no-induction protocol in anticalcineurin-based immunosuppression using very
low-dose steroids.
REVISTA
/ JOURNAL: - Transplant Proc 2001 Jun;33(4 Suppl):3S-10S.
AUTORES
/ AUTHORS: - Charpentier B
INSTITUCIÓN
/ INSTITUTION: - University Hospital of Bicetre, Le
Kremlin-Bicetre, France.
----------------------------------------------------
[147]
TÍTULO / TITLE: - A new immunosuppressive
protocol for lung transplantation: early promising results.
REVISTA
/ JOURNAL: - Transplant Proc 2003 Mar;35(2):625-6.
AUTORES
/ AUTHORS: - Aravot D; Saute M; Eidelman L; Berman M;
Bendayan D; Orlov B; Raanani E; Sahar G; Kogan A; Vidne B; Kramer M
INSTITUCIÓN
/ INSTITUTION: - Heart-Lung Transplant Unit, Department of
Cardiothoracic Surgery, Sackler Faculty of Medicine, Rabin Medical Center,
Beilinson Campus, Petach Tikva, Israel.
----------------------------------------------------
[148]
TÍTULO / TITLE: - Immunosuppressive therapy
and post-transplantation diarrhea.
REVISTA
/ JOURNAL: - Clin Transplant 2001;15 Suppl 4:23-8.
AUTORES
/ AUTHORS: - Pescovitz MD; Navarro MT
INSTITUCIÓN
/ INSTITUTION: - Department of Surgery, Indiana University,
Indianapolis, USA. mpescov@iupui.edu
RESUMEN
/ SUMMARY: - Gastrointestinal complications, including
diarrhea, are among the anticipated adverse events secondary to
immunosuppression. The reported overall rate of diarrhea may be affected by
drug-specific effects, dose-response effects, interactions with other
medications, drug formulation, the length of study follow-up, reporting bias
and population characteristics such as ethnicity and baseline disease,
including transplant organ type. The true incidence of diarrhea is often
difficult to assess from the numerous published clinical trials. A number of
deficiencies, including self-reporting, interstudy comparisons, lack of
blinding, concomitant medications and a general lack of standardization and quantification
of diarrhea may greatly obscure comparisons among the different
immunosuppressive medications. This review considers each of these factors in
assessing the overall incidence of post-transplantation diarrhea for the
various immunosuppressive medications currently in use. N. Ref:: 15
----------------------------------------------------
[149]
TÍTULO / TITLE: - Nonmyeloablative
hematopoietic cell transplantation. Replacing high-dose cytotoxic therapy by
the graft-versus-tumor effect.
REVISTA
/ JOURNAL: - Ann N Y Acad Sci 2001 Jun;938:328-37;
discussion 337-9.
AUTORES
/ AUTHORS: - Feinstein L; Sandmaier B; Maloney D;
McSweeney PA; Maris M; Flowers C; Radich J; Little MT; Nash RA; Chauncey T;
Woolfrey A; Georges G; Kiem HP; Zaucha JM; Blume KG; Shizuru J; Niederwieser D;
Storb R
INSTITUCIÓN
/ INSTITUTION: - Fred Hutchinson Cancer Research Center,
1100 Fairview Avenue N., D1-100, P.O. Box 19024, Seattle, Washington
98109-1024, USA. lfeinste@fhcrc.org
RESUMEN
/ SUMMARY: - Conventional allografting produces
considerable regimen-related toxicities that generally limit this treatment to
patients younger than 55 years and in otherwise good medical condition. T
cell-mediated graft-versus-tumor (GVT) effects are known to play an important
role in the elimination of malignant disease after allotransplants. A minimally
myelosuppressive regimen that relies on immunosuppression for allogeneic
engraftment was developed to reduce toxicities while optimizing GVT effects.
Pre-transplant total-body irradiation (200 cGy) followed by post-transplant
immunosuppression with cyclosporine (CSP) and mycophenolate mofetil (MMF)
permitted human leukocyte antigen (HLA)-matched sibling donor hematopoietic
cell engraftment in 82% of patients (n = 55) without prior high-dose therapy.
The addition of fludarabine (90 mg/m2) facilitated engraftment in all 28
subsequent patients. Overall, fatal progression of underlying disease occurred
in 20% of patients after transplant. Non-relapse mortality occurred in 11% of
patients. Toxicities were low. Grade 2-4 acute graft-versus-host disease (GVHD)
associated with primary engraftment developed in 47% of patients, and was
readily controlled in all but two patients. Donor lymphocyte infusions (DLI) were
not very effective at converting a low degree of mixed donor/host chimerism to
full donor chimerism; however, the addition of fludarabine reduced the need for
DLI. With a median follow-up of 244 days, 68% of patients were alive, with 42%
of patients in complete remission, including molecular remissions. Remissions
occurred gradually over periods of weeks to a year. If long-term efficacy is
demonstrated, such a strategy would expand treatment options for patients who
would otherwise be excluded from conventional allografting. N. Ref:: 51
----------------------------------------------------
[150]
TÍTULO / TITLE: - Induction versus
non-induction protocols in anti-calcineurin-based immunosuppression.
REVISTA
/ JOURNAL: - Transplant Proc 2001 Nov-Dec;33(7-8):3334-6.
AUTORES
/ AUTHORS: - Charpentier B
INSTITUCIÓN
/ INSTITUTION: - Service de Nephrologie, University
Hospital of Bicetre, Bicetre, France.
----------------------------------------------------
[151]
TÍTULO / TITLE: - Intestinal and
multivisceral transplantation.
REVISTA
/ JOURNAL: - World J Surg 2002 Feb;26(2):226-37. Epub
2001 Dec 21.
●●
Enlace al texto completo (gratuito o de pago) 1007/s00268-001-0210-5
AUTORES
/ AUTHORS: - Kato T; Ruiz P; Thompson JF; Eskind LB;
Weppler D; Khan FA; Pinna AD; Nery JR; Tzakis AG
INSTITUCIÓN
/ INSTITUTION: - Division of Transplantation, University of
Miami School of Medicine, Miami, Florida 33136, USA.
RESUMEN
/ SUMMARY: - Intestinal transplantation has been
gradually instituted in the management of intestinal failure. More than 200
cases including isolated intestinal transplant, liver/intestinal transplant,
and multivisceral transplant have been performed worldwide,with 1-year graft
and patient survival rates of 66% and 54%,respectively. Indications for the
procedure include short bowel syndrome and functional abnormalities secondary
to a variety of diseases or conditions. Tacrolimus-based immunosuppression
regimens have been used universally with improved outcomes. The major
contributors to the morbidity and mortality include rejection,infection, and
technical complications. Of those, control of rejection remains the most
difficult dilemma and it will be the key to improved patient and graft survival. N. Ref:: 60
----------------------------------------------------
[152]
TÍTULO / TITLE: - Options for induction
immunosuppression in liver transplant recipients.
REVISTA
/ JOURNAL: - Drugs 2002;62(7):995-1011.
AUTORES
/ AUTHORS: - Moser MA
INSTITUCIÓN
/ INSTITUTION: - Multi-Organ Transplant Program, London
Health Sciences Center, 339 Windermere Road, London, Ontario N6A 5A5, Canada.
RESUMEN
/ SUMMARY: - Immunosuppression administered in the
early postoperative period following liver transplantation plays a crucial role
in the survival of the graft and the patient. The introduction of cyclosporin
was an important landmark in transplantation, and to this day, calcineurin
inhibitors form the basis of most induction immunosuppression regimens. New drugs
are being developed which are more specifically targeted to prevention of
rejection, and multiple drug combinations have been proposed as a means of
reducing the adverse effects of individual drugs. Azathioprine and the newer
antimetabolite mycophenolate mofetil have been added to calcineurin
inhibitor-based regimens with varying amounts of success. Antibody induction
has evolved as a potent form of immunosuppression as well as a means of
avoiding certain adverse effects, particularly nephrotoxicity. The numerous
adverse effects encountered with polyclonal preparations have been reduced with
the development of more specific monoclonal antibodies such as muromonab CD3
(OKT3) or interleukin (IL)-2 receptor (IL-2R) antagonists. The anti-IL-2R
antibody preparations basiliximab and daclizumab have shown excellent early
results due to their potent yet highly targeted immunosuppressive effect and
minimal adverse effects. Further study is needed to determine the most
appropriate dosage, timing and patient population for these new drugs in the
setting of liver transplantation. Although a number of different induction
regimens have been described, no single protocol is suitable for all liver
transplant recipients. Rather, certain regimens have advantages that could favour
their use in a specific subgroup of patients. A number of clinical trials are
underway to identify new, more specific drugs and combinations which could be
useful in induction immunosuppression. N.
Ref:: 46
----------------------------------------------------
[153]
TÍTULO / TITLE: - Structures of
immunophilins and their ligand complexes.
REVISTA
/ JOURNAL: - Curr Top Med Chem 2003;3(12):1392-409.
AUTORES
/ AUTHORS: - Dornan J; Taylor P; Walkinshaw MD
INSTITUCIÓN
/ INSTITUTION: - Structural Biochemistry, The University of
Edinburgh, Michael Swann Building, King’s Buildings, Edinburgh EH9 3JR,
Scotland, UK. M.WALKINSHAW@ed.ac.uk
RESUMEN
/ SUMMARY: - This review includes an analysis of
available X-ray and NMR structures of both members of the immunophilin family;
cyclophilins and the FK-506 binding proteins (FKBPs). Available structures are
compared and contrasted to highlight different structural features seen both
within and between species. Each immunophilin family has been structurally
characterised with a variety of small molecule ligands, principally
immunosuppressive drugs and their analogues and an overview of these complexes
is also presented. Currently the Protein Data Base contains over 60 entries for
cyclophilins and over 40 entries for FKBPs. A number of FKBP related structures
are also available including structures of MIP (Macrophage Infectivity
Potentiator protein) from Legionella pneumophila and Trypanosoma cruzi and
Trigger Factor from Mycoplasma genitalium. For all structures discussed in the
review a summary of the available biological data is also presented. N. Ref:: 106
----------------------------------------------------
[154]
TÍTULO / TITLE: - Transplant immunology.
REVISTA
/ JOURNAL: - J Pediatr Surg 2003 Sep;38(9):1275-80.
AUTORES
/ AUTHORS: - Aw MM
INSTITUCIÓN
/ INSTITUTION: - Department of Paediatrics and Liver
Transplant Unit, National University Hospital, Singapore.
RESUMEN
/ SUMMARY: - The immune response to an allogeneic
transplanted organ is T-cell dependent. It is governed partially by the context
in which the T-cell encounters the antigen and can range from apoptosis,
anergy, and neglect to full activation. The current armamentarium of
immunosuppressive agents acts to inhibit the various steps of this T-cell
activation pathway; at the level of the T-cell receptor (monoclonal antibodies
such as OKT3), intracellular signally (calcineurine-inhibitors), DNA synthesis
(azathioprine), or to cause lymphocyte depletion (ATG, ALG). Most protocols use
a combination of agents for induction and maintenance immunosuppression.
Although successful in preventing and treating allograft rejection, they are
not without side effects. With improved patient and graft survival rates,
adverse events such as hypertension, nephrotoxicity, hyperglycaemia, and
lymphoproliferative disease become increasingly important issues. Newer drugs
(IL-2 receptor antagonists, mycophenolate mofetil, rapamycin) have been
introduced in an attempt to spare or avoid these adverse effects. Inducing
graft tolerance and long-term drug-free survival is the goal of transplant
immunologists. Postulated mechanisms include clonal deletion, anergy, and
immunoredirection. Although a number of methods have been tested experimentally,
none has been proven to induce tolerance for routine clinical use.
Immunosuppression remains the cornerstone of the success of organ
transplantation. Until investigators are able to induce tolerance in their
transplant recipients or develop a tolerance assay, they would need to continue
to tailor their immunosuppressive therapy according to the risk profile of the
individual recipient. N.
Ref:: 38
----------------------------------------------------
[155]
TÍTULO / TITLE: - Novel therapies for anti-neutrophil
cytoplasmic antibody-associated vasculitis.
REVISTA
/ JOURNAL: - Curr Opin Nephrol Hypertens 2001
Mar;10(2):211-7.
AUTORES
/ AUTHORS: - Tervaert JW; Stegeman CA; Kallenberg CG
INSTITUCIÓN
/ INSTITUTION: - University Hospital Maastricht, Department
of Clinical and Experimental Immunology, Maastricht, the Netherlands. jw.cohentervaert@immuno.unimaas.nl
RESUMEN
/ SUMMARY: - High-dose corticosteroids in combination
with cytotoxic drugs are universally accepted as the initial approach in
vasculitides that are associated with anti-neutrophil cytoplasmic antibodies.
Cyclophosphamide is the most effective cytotoxic drug and is used in more
severe cases. Because cyclophosphamide has more severe short- and long-term
side-effects than methotrexate, methotrexate is used in less severe cases. New
prospects for the treatment of vasculitis include novel immunosuppressive
agents (e.g. mycophenolate, 15-deoxyspergualin, and leflunomide), sequential chemotherapy
(e.g. cyclophosphamide followed by azathioprine or cyclophosphamide followed by
methotrexate), intravenous immunoglobulin, tumour necrosis factor-alpha
directed therapy, anti-lymphocyte directed therapy (e.g. antithymocyte globulin
or anti CD52/anti CD4 antibodies), anti-adhesion molecule directed therapy
(e.g. anti-CD18 or intercellular adhesion molecule-1 antisense) or
immunoablation using high-dose cytotoxic medication with or without stem cell
rescue. N. Ref:: 60
----------------------------------------------------
[156]
TÍTULO / TITLE: - Role of
anti-interleukin-2 receptor antibodies in kidney transplantation.
REVISTA
/ JOURNAL: - BioDrugs 2001;15(10):655-66.
AUTORES
/ AUTHORS: - Cibrik DM; Kaplan B; Meier-Kriesche HU
INSTITUCIÓN
/ INSTITUTION: - University of Michigan, Ann Arbor,
Michigan 48109-0704, USA. dcibrik@umich.edu
RESUMEN
/ SUMMARY: - From the early 1960s, the mainstay of
immunosuppression for kidney transplantation has been corticosteroids. Since
then, many new drugs have been developed to maintain the renal allograft.
Current maintenance immunosuppression commonly consists of corticosteroids,
antiproliferative agents and calcineurin inhibitors (e.g. cyclosporin). More
recently, antihuman antibodies, either monoclonal or polyclonal, have been
developed to use for induction at the time of transplantation or to treat
rejection. With the advances in molecular technology, a new class of antihuman
antibodies [the anti-interleukin-2 receptor (IL-2R) antibodies] has emerged
that incorporate a murine antigen-binding site on to a human immunoglobulin
backbone. Such methodology creates antihuman antibodies with high affinity for
the epitope and with prolonged serum antibody half-lives. Interleukin-2 and its
receptor are central to lymphocyte activation and are the main targets of
calcineurin inhibitors. In addition, the anti-IL-2R antibodies inhibit a key
target in immune activation. Daclizumab and basiliximab have been shown to
significantly reduce the incidence of acute rejection in kidney
transplantation. Since these anti-IL-2R antibodies are well tolerated and since
calcineurin inhibitors are intrinsically nephrotoxic, anti-IL-2R antibodies
have been used in an attempt to avoid cyclosporin after transplantation. Data
from clinical trials seem to indicate that the addition of an anti-IL-2R
antibody is not sufficient to warrant complete withdrawal of calcineurin
inhibitors for more than a very short period after transplantation. A more
promising role for anti-IL-2R antibodies may be in renal transplant recipients
with delayed graft function (DGF). Recent data on the use of either low-dose
calcineurin inhibitors or sirolimus (rapamycin) in conjunction with the
anti-IL-2R antibodies for patients with DGF showed no increased risk of acute
rejection. Long-term graft survival with use of these low-dose calcineurin
inhibitor protocols has yet to be established.
N. Ref:: 41
----------------------------------------------------
[157]
- Castellano -
TÍTULO / TITLE:Medicamentos inmunosupresores en la
esclerosis multiple. Immunosuppressive medication in multiple sclerosis.
REVISTA
/ JOURNAL: - Rev Neurol. Acceso gratuito al texto
completo.
●●
Enlace a la Editora de la Revista http://www.revneurol.com/LinkOut/formMedLine.asp?Refer=2003226&Revista=Revneurol
●●
Cita: Revista de Neurologia: <> 2002 Dec 16-31;35(12):1154-8.
AUTORES
/ AUTHORS: - Garcia Merino JA
INSTITUCIÓN
/ INSTITUTION: - Servicio de Neurologia, Clinica Puerta del
Hierro, Madrid, España. gmerino@meditex.es
RESUMEN
/ SUMMARY: - Immunosuppressive drugs have been used for
decades in the treatment of multiple sclerosis. The recent availability of
immunomodulators has caused a major change in the treatment of this disease,
but has not meant the disappearance of the use of immunosuppressive drugs, some
of which (such as mitoxantrone) have been introduced recently. At present, it
is difficult to assess the precise indications for these drugs, since most
efficacy studies were made before the availability of magnetic resonance
imaging, on criteria which are now considered obsolete. Independently of their
value in monotherapy, immunosuppressants may probably be useful in combination
with immunomodulators. We review the experience with the most widely used
immunosuppressants and mention those drugs which might be used in the near
future. N. Ref:: 36
----------------------------------------------------
[158]
TÍTULO / TITLE: - Rejection-free protocol
using sirolimus-tacrolimus combination for pediatric renal transplant
recipients.
REVISTA
/ JOURNAL: - Transplant Proc 2002 Aug;34(5):1942-3.
AUTORES
/ AUTHORS: - El-Sabrout R; Weiss R; Butt F; Delaney V;
Qadir M; Hanson P; Butt K
INSTITUCIÓN
/ INSTITUTION: - Departments of Transplantation/Vascular
Surgery, New York Medical College, Valhalla, New York, USA.
----------------------------------------------------
[159]
TÍTULO / TITLE: - The development of
immunosuppression: the rapamycin milestone.
REVISTA
/ JOURNAL: - Transplant Proc 2003 May;35(3
Suppl):15S-17S.
AUTORES
/ AUTHORS: - Calne RY
INSTITUCIÓN
/ INSTITUTION: - Department of Surgery, University of
Cambridge, Addenbrook Hospital, Cambridge, UK.
N. Ref:: 22
----------------------------------------------------
[160]
TÍTULO / TITLE: - Transcriptional
reprogramming during T helper cell differentiation.
REVISTA
/ JOURNAL: - Immunol Res 2001;23(2-3):193-204.
AUTORES
/ AUTHORS: - Aune TM
INSTITUCIÓN
/ INSTITUTION: - Department of Medicine, Vanderbilt
University School of Medicine, Nashville, TN 37232, USA. thomas.aune@mcmail.vanderbilt.edu
RESUMEN
/ SUMMARY: - Our laboratory employs reporter transgenic
mice as model systems to study the transcriptional reprogramming that
accompanies T helper cell differentiation. These studies demonstrate that
changes in the activity of simple transcriptional elements associated with the
IFN-gamma gene can recapitulate alterations in gene expression. In addition,
our studies have revealed a key role for the transcription factor, CAMP
response element binding protein (CREB), in the protection of differentiating T
cells from apoptosis. Together, these findings further our understanding of the
logic employed by T cells to alter gene expression profiles in response to
differentiation signals. N.
Ref:: 49
----------------------------------------------------
[161]
TÍTULO / TITLE: - In utero exposure to
immunosuppressive drugs: experimental and clinical studies.
REVISTA
/ JOURNAL: - Pediatr Nephrol 2002 Feb;17(2):121-30.
AUTORES
/ AUTHORS: - Tendron A; Gouyon JB; Decramer S
INSTITUCIÓN
/ INSTITUTION: - Hopital d’Enfants, Service de
Neonatologie, 10 boulevard Mal de Lattre de Tassigny, 21034 Dijon Cedex,
France. anais.tendron@planetb.fr
RESUMEN
/ SUMMARY: - Over the last few decades, the number of
pregnant women under immunosuppressive (IS) therapy following transplantation
or autoimmune diseases has increased. At first, IS drugs, including prednisone,
azathioprine, and cyclosporine A were used, but now new molecules such as
tacrolimus and mycophenolate mofetil have appeared. These IS drugs cross the
placental barrier and enter into the fetal circulation, which poses a risk for
fetal development. Experimental data have shown that IS drugs often have
deleterious effects on fetuses, while human data have reported an increased
rate of abortion, prematurity, intrauterine growth retardation (IUGR), and low
birth weight, without significant increases in malformation rates. However,
only limited information is available about the newly used molecules. Although
fetal and neonatal data are reassuring, long-term effects of IS drugs on
fertility, immune response and renal function, as well as the consequences of
prematurity and IUGR, should be monitored.
N. Ref:: 78
----------------------------------------------------
[162]
TÍTULO / TITLE: - Good fungi gone bad:
the corruption of calcineurin.
REVISTA
/ JOURNAL: - Bioessays 2002 Oct;24(10):894-903.
●●
Enlace al texto completo (gratuito o de pago) 1002/bies.10157
AUTORES
/ AUTHORS: - Fox DS; Heitman J
INSTITUCIÓN
/ INSTITUTION: - Department of Molecular Genetics and
Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
RESUMEN
/ SUMMARY: - Calcineurin is a
Ca(2+)/calmodulin-activated protein phosphatase that is conserved in
eukaryotes, from yeast to humans, and is the conserved target of the
immunosuppressive drugs cyclosporin A (CsA) and FK506. Genetic studies in yeast
and fungi established the molecular basis of calcineurin inhibition by the
cyclophilin A-CsA and FKBP12-FK506 complexes. Calcineurin also functions in
fungi to control a myriad of physiological processes including cell cycle
progression, cation homeostasis, and morphogenesis. Recent investigations into
the molecular mechanisms of pathogenesis in Candida albicans and Cryptococcus
neoformans, two fungi that cause life-threatening infections in humans, have
revealed an essential role for calcineurin in morphogenesis, virulence, and
antifungal drug action. Novel non-immunosuppressive analogs of the calcineurin
inhibitors CsA and FK506 that retain antifungal activity have been identified
and hold promise as candidate antifungal drugs. In addition, comparisons of
calcineurin function in both fungi and humans may identify fungal-specific
components of calcineurin-signaling pathways that could be targeted for
therapy, as well as conserved elements of calcium signaling events. N. Ref:: 88
----------------------------------------------------
[163]
TÍTULO / TITLE: - The limitations of
calcineurin and mTOR inhibitors: new directions for immunosuppressive
strategies.
REVISTA
/ JOURNAL: - Transplant Proc 2002 Feb;34(1):130-3.
AUTORES
/ AUTHORS: - Kahan BD
INSTITUCIÓN
/ INSTITUTION: - Division of Organ Transplantation,
Department of Surgery, The University of Texas Medical School, Houston, Texas
77030, USA. N. Ref:: 76
----------------------------------------------------
[164]
TÍTULO / TITLE: - Cardiovascular
toxicities of immunosuppressive agents.
REVISTA
/ JOURNAL: - Am J Transplant 2002 Oct;2(9):807-18.
AUTORES
/ AUTHORS: - Miller LW
INSTITUCIÓN
/ INSTITUTION: - Cardiovascular Division, University of
Minnesota, Minneapolis, USA. mille278@tc.umn.edu
RESUMEN
/ SUMMARY: - Cardiovascular disease is one of the major
causes of morbidity and mortality following solid organ transplantation. Many
of the current immunosuppressive drugs are associated with an increase of one
or more risk factors for the development of atherosclerosis. This review
compares the mechanism by which individual immunosuppressive agents may impact
on these risk factors and the differential contribution of cyclosporine,
tacrolimus, mycophenolate, azathioprine, and Rapamycin to these individual risk
factors. Attention to the potential cardiovascular toxicities of individual
immunosuppressive agents may help design strategies for maintenance of
immunosuppression tailored to individual patients. N. Ref:: 139
----------------------------------------------------
[165]
TÍTULO / TITLE: - Intracranial hemorrhage
in neuro-Behcet’s syndrome.
REVISTA
/ JOURNAL: - Intern Med 2002 Sep;41(9):692-5.
AUTORES
/ AUTHORS: - Kikuchi S; Niino M; Shinpo K; Terae S;
Tashiro K
INSTITUCIÓN
/ INSTITUTION: - Department of Neurology, Hokkaido
University Graduate School of Medicine, Sapporo.
RESUMEN
/ SUMMARY: - OBJECTIVE: Most cerebrovascular
disturbances in Behcet’s syndrome are occlusive in nature, while hemorrhage is
rare. In this paper, we report three cases of neuro-Behcet’s syndrome
presenting with intracerebral hemorrhaging, and discuss the possible causes as
they relate to cyclosporine treatment. PATIENTS: Three cases of neuro-Behcet’s
syndrome presented with intracranial hemorrhage. One patient had been taking
cyclosporine, and the other two patients had never taking cyclosporine.
RESULTS: Together with previous reports, these cases suggest that there are two
types of intracranial hemorrhage in neuro-Behcet’s syndrome. One type occurs in
the center of a lesion and during the acute phase of the disease, while the
other occurs in the peripheral lesion and during the subacute phase.
CONCLUSIONS: It appears that the intracranial hemorrhages in neuro-Behcet’s
syndrome can be divided into two groups. It is possible that the vascular
pathologies caused by Behcet’s syndrome and by cyclosporine conspire to induce
CNS hemorrhaging in some cases. N.
Ref:: 19
----------------------------------------------------
[166]
TÍTULO / TITLE: - Endocrine aspects of
neurosarcoidosis.
REVISTA
/ JOURNAL: - J Endocrinol Invest 2002
Jul-Aug;25(7):650-62.
AUTORES
/ AUTHORS: - Murialdo G; Tamagno G
INSTITUCIÓN
/ INSTITUTION: - Department of Endocrinological and
Metabolic Sciences, University of Genova, Italy. gmurialdo@unige.it
RESUMEN
/ SUMMARY: - The involvement of the hypothalamus and/or
pituitary gland by granulomatous, infiltrative or autoimmune diseases is a rare
condition of non-tumoral-non-vascular acquired hypothalamic dysfunction and
hypopituitarism. In this paper, we present the case of a 26-year-old woman, who
showed an amenorrhea-galactorrhea syndrome with hypogonadotropic hypogonadism
due to an isolated hypothalamic-peduncular localization of neurosarcoidosis.
Acquired GH deficiency was also demonstrated. This clinical case provided the
opportunity for a review of the endocrine aspects linked to brain infiltrative
diseases that may affect the hypothalamic-pituitary function, with a focus upon
neurosarcoidosis. Sarcoidosis is a pathogen-free granulomatous disease that
affects both the central and peripheral nervous system in 5-16% of patients. In
most cases, such involvement by sarcoidosis occurs within a multi-systemic
disease, but disease localization limited to the nervous system may also be
observed. Endocrine manifestations of neurosarcoidosis disclose
“chameleon-like” clinical pictures, which are usually expressed by the evidence
of hypothalamic dysfunction, diabetes insipidus, adenopituitary failure,
amenorrhea-galactorrhea syndrome, in isolated fashion or variedly combined.
More rarely, inappropriate anti-diuretic hormone secretion, isolated secondary
hypothyroidism, adrenal insufficiency or altered counter-regulation of glucose
homeostasis have been reported. Neurosarcoidosis is often hard to diagnose,
especially when the neurological localization of the disease is not accompanied
by other systemic localizations or by specific signs of the disease, and when
the lesion is too deep to obtain bioptic confirmation. The study of
cerebrospinal fluid and blood lymphocyte sub-populations, integrated by MRI and
nuclear scans (67GalIium uptake and 111Indium-pentetreotide, Octreoscan), may
be helpful for a correct diagnosis. Therapy with corticosteroid and
immunosuppressive drugs, such as cyclosporine A, and other treatment approaches
to neurosarcoidosis are also accounted for.
N. Ref:: 111
----------------------------------------------------
[167]
TÍTULO / TITLE: - Acquired anti-FVIII
inhibitors in children.
REVISTA
/ JOURNAL: - Haemophilia 2002 Jan;8(1):28-32.
AUTORES
/ AUTHORS: - Moraca RJ; Ragni MV
INSTITUCIÓN
/ INSTITUTION: - The Department of Medicine, Division of
Hematology/Oncology, University of Pittsburgh Medical Center, PA, USA.
RESUMEN
/ SUMMARY: - Acquired inhibitors to FVIII (anti-FVIII)
are uncommon in children. An acquired anti-FVIII developed in a previously
healthy 4-year-old boy treated with penicillin for streptococcal pharyngitis.
Aspirin prophylaxis begun for suspected rheumatic fever led to compartment syndromes
of all four extremities, which resolved with high-dose FVIII and surgical
decompression. Anti-FVIII in this patient, and the five additional cases
identified in a survey of 160 haemophilia treatment centres, occurred at a
median age of 8 years, with median initial and peak titres of 4.6 and 6.9
Bethesda Units (BU), respectively. All six presented with bleeding, including
haematomas (three intramuscular, one intracranial), and ecchymoses in three.
The median baseline FVIII was 0.05 U mL(-1), and the median baseline activated
partial thromboplastin time (APTT) was 79.8 s. The inhibitor resolved
completely in five patients (83%) within a median 5 months, after treatment
with FVIII concentrate, steroids, cytoxan, methotrexate, and no treatment. The
inhibitor persisted in the patient with Goodpasture’s disease, despite
steroids, cytoxan, cyclosporin, and intravenous gamma globulin. Aspirin
therapy, in two, worsened ongoing bleeding. The association of penicillin-like
drugs in this and three other cases in the literature suggest that to avoid
potential catastrophic bleeding, it is prudent to obtain an APTT prior to
initiating aspirin for suspected rheumatic fever. In conclusion, acquired
anti-FVIII inhibitors in children may cause severe bleeding, and remit in the
majority after FVIII and/or immunosuppressive therapy. N. Ref:: 21
----------------------------------------------------
[168]
TÍTULO / TITLE: - Drug-nutrient
interactions in transplant recipients.
REVISTA
/ JOURNAL: - JPEN J Parenter Enteral Nutr 2001
May-Jun;25(3):132-41.
AUTORES
/ AUTHORS: - Chan LN
INSTITUCIÓN
/ INSTITUTION: - Department of Pharmacy Practice &
Medicine, Colleges of Pharmacy and Medicine, University of Illinois at Chicago,
60612, USA. neander@uic.edu
RESUMEN
/ SUMMARY: - Drug-nutrient interaction refers to an
alteration of kinetics or dynamics of a drug or a nutritional element, or a
compromise in nutritional status as a result of the addition of a drug. The
potentials for drug-nutrient interaction increase with the number of drugs
taken by the patient. Organ transplant recipients are therefore at high risk
for drug-nutrient interactions because multiple medications are used to manage
graft rejection, opportunistic infections, and other associated complications.
Unrecognized or unmanaged drug-nutrient interactions in this patient population
can have an adverse impact on their outcomes. This paper reviews the importance
of recognizing drug-nutrient interaction when using cyclosporine-based regimens. N. Ref:: 74
----------------------------------------------------
[169]
TÍTULO / TITLE: - Advances in composite
tissue allograft transplantation as related to the hand and upper extremity.
REVISTA
/ JOURNAL: - J Hand Surg [Am] 2002 Jul;27(4):565-80.
AUTORES
/ AUTHORS: - Siemionow M; Ozer K
INSTITUCIÓN
/ INSTITUTION: - Department of Plastic Surgery, The
Cleveland Clinic Foundation, A60, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
RESUMEN
/ SUMMARY: - The clinical transplantation of composite tissue
allografts (CTA) such as human hand or larynx is stimulating discussions among
surgeons at national and international forums on the indications, ethical
aspects, toxic effects of immunosuppression, and functional results of the
first reported cases of unilateral and bilateral hand transplantation. This
Clinical Perspective article presents the latest advances in clinical and
experimental research related to the field of CTAs. The article presents the
historic aspects of CTA, a broad view of the current state of composite tissue
transplantation, the mechanism of allograft rejection, current experimental and
clinical protocols, and, finally, the future prospects of the standard use of
CTAs. It is clear that there is a substantial demand for routine use of CTAs
but the treatment protocols need to be optimized and the functional outcomes
need to be improved. N.
Ref:: 125
----------------------------------------------------
[170]
TÍTULO / TITLE: - Cutaneous T-cell
lymphoma in a cardiac transplant recipient.
REVISTA
/ JOURNAL: - Tex Heart Inst J. Acceso gratuito al texto
completo.
●●
Enlace a la Editora de la Revista http://texasheartinstitute.org/journal.html
●●
Cita: Texas Heart Institute Journal: <> 2001;28(3):203-7.
AUTORES
/ AUTHORS: - McMullan DM; Radovaneevic B; Jackow CM;
Frazier OH; Duvic M
INSTITUCIÓN
/ INSTITUTION: - Texas Heart Institute and St Luke s
Episcopal Hospital Houston, 77225-0345, USA.
RESUMEN
/ SUMMARY: - Mycosis fungoides, an uncommon form of
cutaneous T-cell lymphoma, arises in the skin and frequently progresses to
generalized lymphadenopathy Although the cause of cutaneous T-cell lymphoma is
unknown, chronic immunosuppression may play a role. A few cases have been reported
in renal transplant recipients; however, ours appears to be the 1st
report of cutaneous T-cell lymphoma in a cardiac transplant recipient. In our
patient, cutaneous manifestations of the disease were noted less than 1 year
after transplantation. Seven years after transplantation, Sezary syndrome, a
variant form of mycosis fungoides, was diagnosed by tissue biopsy and flow
cytometry analysis. Photopheresis improved symptoms but was not well tolerated
because of hemodynamic sequelae. Psoralen and ultraviolet A therapy also
improved the patient’s skin condition, but a generalized lymphadenopathy
developed. The maintenance immunosuppressive regimen was changed from
cyclosporine (3 mg/kg/day) and azathioprine to cyclosporine (1.5 mg/kg/day) and
cyclophosphamide. Although effective in the short-term, the results of this
therapeutic strategy could not be fully evaluated because the patient died of
acute myocardial infarction. N.
Ref:: 25
----------------------------------------------------
[171]
TÍTULO / TITLE: -
Neurotrauma/neurodegeneration and mitochondrial dysfunction.
REVISTA
/ JOURNAL: - Prog Brain Res 2002;137:171-6.
AUTORES
/ AUTHORS: - Frantseva M; Perez Velazquez JL; Tonkikh
A; Adamchik Y; Carlen PL
INSTITUCIÓN
/ INSTITUTION: - Toronto Western Research Institute, Room
12-413, Hospital for Sick Children, Department of Neurology, Toronto,
Canada. N. Ref:: 47
----------------------------------------------------
[172]
TÍTULO / TITLE: - Macrophage activation
syndrome.
REVISTA
/ JOURNAL: - Curr Opin Rheumatol 2002 Sep;14(5):548-52.
AUTORES
/ AUTHORS: - Ravelli A
INSTITUCIÓN
/ INSTITUTION: - Pediatria II, Istituto G. Gaslini,
Universita di Genova, Italy. angeloravelli@ospedale-gaslini.ge.it
RESUMEN
/ SUMMARY: - Macrophage activation syndrome (MAS) is a
serious complication of childhood systemic inflammatory disorders that is
thought to be caused by excessive activation and proliferation of T lymphocytes
and macrophages. Recent findings in hemophagocytic lymphohistiocytosis, a
disease that is clinically similar to MAS, highlight the possible pathogenetic
role of a defective function of perforin, a protein involved in the cytolytic
processes and control of lymphocyte proliferation. Although the clinical
features of MAS have been well documented, early diagnosis can be difficult.
Measurement of the serum ferritin level may assist in the diagnosis and may be
a useful indicator of disease activity, therapy response, and prognosis. The
recognition that MAS belongs to the secondary or reactive hemophagocytic
syndromes has led to the proposal to rename it according to the contemporary
classification of histiocytic disorders. Cyclosporin A has been found effective
in patients with corticosteroid-resistant MAS. A recent report has suggested
that etanercept may be a useful adjunctive therapeutic agent. N. Ref:: 35
----------------------------------------------------
[173]
TÍTULO / TITLE: - In utero exposure to
immunosuppressive drugs.
REVISTA
/ JOURNAL: - Biol Neonate 2002;81(2):73-81.
AUTORES
/ AUTHORS: - Prevot A; Martini S; Guignard JP
INSTITUCIÓN
/ INSTITUTION: - Department of Pediatrics, Pediatric
Nephrology Unit, Centre Hospitalier Universitaire Vaudois, Lausanne,
Switzerland. prevotanne@hotmail.com
RESUMEN
/ SUMMARY: - The number of pregnant women receiving
immunosuppressants for anti-rejection therapy or autoimmune diseases is
increasing. All immunosuppressive drugs cross the placenta, raising questions
about the long-term outcome of the children exposed in utero. There is no
higher risk of congenital anomalies. However, an increased incidence of
prematurity, intrauterine growth retardation (IUGR) and generally low birth
weight has been reported, as well as maternal hypertension and preeclampsia.
The most frequent neonatal complications are those associated with prematurity
and IUGR, as well as adrenal insufficiency with corticosteroids, immunological
disturbances with azathioprine and cyclosporine, and hyperkalemia with
tacrolimus. The long-term follow-up of infants exposed to immunosuppressants in
utero is still limited and experimental studies raise the question whether
there could be an increased incidence at adult age of some pathologies including
renal insufficiency, hypertension and diabetes. N. Ref:: 58
----------------------------------------------------
[174]
TÍTULO / TITLE: - Immunologic targets for
currently available immunosuppressive agents: what is the optimal approach for
children?
REVISTA
/ JOURNAL: - Semin Nephrol 2001 Sep;21(5):508-20.
AUTORES
/ AUTHORS: - Sho M; Samsonov DV; Briscoe DM
INSTITUCIÓN
/ INSTITUTION: - Division of Nephrology, Department of
Medicine, Children’s Hospital and Harvard Medical School, Boston, MA 02115,
USA.
RESUMEN
/ SUMMARY: - In this review, the authors discuss
immunologic targets and events in T cells that are dysregulated by commonly
used immunosuppressive agents. These include a description of glucocortcoid
receptors as well as targets of glucocorticoids, targets of cyclosporine and
FK506, and the mammalian target of rapamycin. In addition, novel antibody-based
targets on T cells and antigen-presenting cells including the IL-2 receptor and
costimulatory molecules are described. Finally, the authors provide a rationale
for an optimal approach to immunosuppression in pediatrics. Because many of the
newer immunosuppressive agents are currently in clinical trials, the “optimal”
immunosuppressive strategy for the next decade is forthcoming. N. Ref:: 122
----------------------------------------------------
[175]
TÍTULO / TITLE: - Safety of the new
macrolide immunomodulators.
REVISTA
/ JOURNAL: - Semin Cutan Med Surg 2001 Dec;20(4):242-9.
AUTORES
/ AUTHORS: - Robinson N; Singri P; Gordon KB
INSTITUCIÓN
/ INSTITUTION: - Department of Dermatology, Northwestern
University, Chicago, IL 60611, USA.
RESUMEN
/ SUMMARY: - With the wide acceptance of cyclosporine
in the treatment of skin disease, there has been an effort to find new
immunomodulating agents with superior safety profiles for use in dermatology.
Among the most promising of the classes are the new macrolide immunomodulators,
including tacrolimus and pimecrolimus. Of these, only tocrolimus has had
widespread use for nondermatologic indications, primarily solid organ
transplantation. Both of these agents have been studied for inflammatory
diseases of the skin. In this article, we review the systemic and topical
toxicities of these macrolide immunomodulators. N. Ref:: 68
----------------------------------------------------
[176]
TÍTULO / TITLE: - Intensive care and
immediate follow-up of children after renal transplantation.
REVISTA
/ JOURNAL: - Transplant Proc 2001 Aug;33(5):2821-4.
AUTORES
/ AUTHORS: - Seikaly MG; Sanjad SA
INSTITUCIÓN
/ INSTITUTION: - Children’s Medical Center of Dallas,
Nephrology Office, Dallas, Texas, USA. N.
Ref:: 16
----------------------------------------------------
[177]
TÍTULO / TITLE: - Neurotoxicity of
immunosuppressive drugs.
REVISTA
/ JOURNAL: - Liver Transpl 2001 Nov;7(11):937-42.
●●
Enlace al texto completo (gratuito o de pago) 1053/jlts.2001.27475
AUTORES
/ AUTHORS: - Wijdicks EF
INSTITUCIÓN
/ INSTITUTION: - Department of Neurology, Mayo Clinic,
Rochester, MN 55905, USA. wijde@mayo.edu
RESUMEN
/ SUMMARY: - The clinical profile of neurotoxicity
caused by immunosuppression has changed. When toxic levels are reached, both
cyclosporine and tacrolimus may produce a clinical spectrum that varies from
tremor and acute confusional state to status epilepticus and major speech or
language abnormalities. Coma has become an unusual manifestation. Magnetic
resonance imaging has been better defined, and abnormalities may be more
widespread than those in the posterior lobes. These white matter lesions are
caused by vasogenic edema, but may lead to apoptosis and cytotoxic edema if
exposure is prolonged. Recent evidence suggests inhibition of a drug-efflux
pump and dysfunction of the blood-brain barrier by enhanced nitric oxide
production. N. Ref:: 50
----------------------------------------------------
[178]
TÍTULO / TITLE: - Signalling pathways in
cardiac myocyte hypertrophy.
REVISTA
/ JOURNAL: - Ann Med 2001 Dec;33(9):611-22.
AUTORES
/ AUTHORS: - Sugden PH
INSTITUCIÓN
/ INSTITUTION: - National Heart and Lung Institute
Division, Faculty of Medicine, Imperial College of Science, Technology and
Medicine, London, UK. p.sugden@ic.ac.uk
RESUMEN
/ SUMMARY: - In response to a requirement for increased
contractile power in vivo, mammalian cardiac myocytes adapt through a
hypertrophic response (cell enlargement in the absence of cell division). This
response can be simulated by exposing isolated myocytes in primary culture to
alpha-adrenergic agonists or the vasoactive peptide, endothelin-1. The
signalling pathways responsible for hypertrophic growth have been actively
studied, and it is likely that reversible protein phosphorylation and
dephosphorylation are involved. Three signalling pathways show particular
potential as regulators of the response, ie protein kinase C (PKC),
mitogen-activated protein kinase (MAPK) cascades, and calcineurin. These
species are thought to regulate the rate and specificity of gene transcription
ultimately through modifying the transactivating activity of nuclear
transcription factors. There are three pertinent MAPK cascades, the
extracellular signal-regulated kinase (ERK) cascade, the c-Jun N-terminal kinase
(JNK or SAPK1) cascade, and the p38-MAPK (SAPK2-5) cascade. PKC participates in
the activation of the ERK cascade but does not contribute significantly to the
activation of the two remaining cascades. Calcineurin (or protein phosphatase
2B) is activated by increases in [Ca2+i] through the [Ca2+]-sensing protein,
calmodulin. In this review, I discuss the evidence for and against the
involvement of these signalling proteins in the induction of myocyte
hypertrophy and emphasize that the ERK cascade should perhaps feature more
widely in the collective consciousness.
N. Ref:: 136
----------------------------------------------------
[179]
TÍTULO / TITLE: - Cyclosporin A as a
model antigen: immunochemical and structural studies.
REVISTA
/ JOURNAL: - J Mol Recognit 2002 Sep-Oct;15(5):277-85.
●●
Enlace al texto completo (gratuito o de pago) 1002/jmr.588
AUTORES
/ AUTHORS: - Altschuh D
INSTITUCIÓN
/ INSTITUTION: - UMR 7100 - CNRS/ULP ‘Biotechnologie des
Interactions Moleculaires’, Ecole Superieure de Biotechnologie de Strasbourg,
Pole API, Bld Sebastien Brandt, 67400 Illkirch, France. daniele.altschuh@esbs.u-strasbg.fr
RESUMEN
/ SUMMARY: - The immunosuppressant drug cyclosporin
(Cs) A is a cyclic undecapeptide which has been used as a model antigen because
structural information and a large number of analogs, modified at each of its
11 positions, were available. This review summarizes immunochemical and crystallographic
studies of the interaction between the Fab of monoclonal antibody R45-45-11 and
Cs. Three points are discussed: (1) the different conformations of CsA and the
question of its biologically active form; (2) the Fab-CsA recognition mechanism;
and (3) the relationship between structure and binding properties of CsA
analogs. N. Ref:: 50
----------------------------------------------------
[180]
TÍTULO / TITLE: - Neurotoxicology of the
brain barrier system: new implications.
REVISTA
/ JOURNAL: - J Toxicol Clin Toxicol 2001;39(7):711-9.
AUTORES
/ AUTHORS: - Zheng W
INSTITUCIÓN
/ INSTITUTION: - College of Physicians and Surgeons,
Columbia University, New York, New York 10032, USA. wz18@columbia.edu
RESUMEN
/ SUMMARY: - The concept of a barrier system in the
brain has existed for nearly a century. The barrier that separates the blood
from the cerebral interstitial fluid is defined as the blood-brain barrier,
while the one that discontinues the circulation between the blood and
cerebrospinal fluid is named the blood-cerebrospinal fluid barrier. Evidence in
the past decades suggests that brain barriers are subject to toxic insults from
neurotoxic chemicals circulating in blood. The aging process and some disease
states render barriers more vulnerable to insults arising inside and outside
the barriers. The implication of brain barriers in certain neurodegenerative
diseases is compelling, although the contribution of chemical-induced barrier
dysfunction in the etiology of any of these disorders remains poorly
understood. This review examines what is currently understood about brain
barrier systems in central nervous system disorders by focusing on
chemical-induced neurotoxicities including those associated with nitrobenzenes,
N-methyl-D-aspartate, cyclosporin A, pyridostigmine bromide, aluminum, lead,
manganese, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, and 3-nitropropionic
acid. Contemporary research questions arising from this growing understanding
show enormous promises for brain researchers, toxicologists, and
clinicians. N. Ref:: 72
----------------------------------------------------
[181]
TÍTULO / TITLE: - Homocysteine levels
among transplant recipients: effect of immunosuppressive protocols.
REVISTA
/ JOURNAL: - Transplant Proc 2001 Sep;33(6):2945-6.
AUTORES
/ AUTHORS: - Mor E; Helfmann L; Lustig S; Bar-Nathan N;
Yussim A; Sela BA
INSTITUCIÓN
/ INSTITUTION: - Department of Transplantation, Rabin
Medical Center, Petach-Tikva, Israel.
----------------------------------------------------
[182]
TÍTULO / TITLE: - Revascularization and
microcirculation of freely grafted islets of Langerhans.
REVISTA
/ JOURNAL: - World J Surg 2001 Apr;25(4):509-15. Epub
2001 Apr 11.
●●
Enlace al texto completo (gratuito o de pago) 1007/s002680020345
AUTORES
/ AUTHORS: - Menger MD; Yamauchi J; Vollmar B
INSTITUCIÓN
/ INSTITUTION: - Institute for Clinical and Experimental
Surgery, University of Saarland, D-66421 Homburg/Saar, Germany.
RESUMEN
/ SUMMARY: - A considerable number of experimental
studies have demonstrated that the reestablishment of an appropriate
microvascular supply is an essential prerequisite for successful pancreatic
islet transplantation. Freely transplanted islets show the first signs of
angiogenesis (i.e., capillary sprout formation and protrusion) as early as 2
days after transplantation, and the entire vascularization process is completed
after 10 to 14 days. Cryopreservation and culture of the isolated islets before
transplantation and hyperglycemia of the transplant recipient seem not to
affect the vascularization process essentially. In addition, immunosuppressive
drugs, such as cyclosporin A and 15-deoxyspergualin, do not or only slightly
inhibit revascularization of syngeneic islets; however, they are not able to
prevent completely xenograft-induced microvascular perfusion failure. In
contrast, novel immunosuppressants (e.g., RS-61443) or dietary supplementation
of the antioxidant vitamin E were shown to prevent microvascular graft
rejection almost completely, including leukocyte recruitment and capillary
perfusion failure. Thus the development of novel strategies to improve
posttransplant islet function should include concepts that accelerate the
vascularization process and protect the newly formed microvasculature from
rejection-mediated injury. The improvement of islet graft vascularization and
the maintenance of adequate microvascular perfusion will contribute to the
increased success of pancreatic islet transplantation. N. Ref:: 91
----------------------------------------------------
[183]
TÍTULO / TITLE: - A view on beta cell
transplantation in diabetes.
REVISTA
/ JOURNAL: - Ann N Y Acad Sci 2002 Apr;958:69-76.
AUTORES
/ AUTHORS: - Pipeleers D; Keymeulen B; Chatenoud L;
Hendrieckx C; Ling Z; Mathieu C; Roep B; Ysebaert D
INSTITUCIÓN
/ INSTITUTION: - Free University of Brussels (VUB),
Brussels, Belgium. Daniel.Pipeleers@vub.ac.be
RESUMEN
/ SUMMARY: - Organ donors also offer a source of
insulin-producing tissue that might be used for the treatment of diabetes.
Clinical protocols for transplantation of this tissue aim for the prevention of
chronic diabetes complications without introducing new serious side effects.
Pancreas and islet cell transplantation are discussed in this perspective. The
future of islet cell implants looks favorable but depends on finding ways to
induce immune tolerance to the donor beta cells. Clinical trials can take
advantage of relevant progress in animal models. In a limited study, recipient
treatment with antilymphocyte antibodies and culture of donor cell preparations
appeared useful to induce a state of operational immune tolerance in type 1
diabetic patients, as indirectly judged by graft survival and by analysis of
auto- and alloreactivities in recipients. Use of cultured beta cell
preparations also allows donor cell recruitment from suboptimal donor organs
and increases the degree of standardization and quality control of islet cell
grafts. The future of these grafts will depend on the development of techniques
for the neogenesis of beta cells. N.
Ref:: 47
----------------------------------------------------
[184]
TÍTULO / TITLE: - Overview of side effects
of immunosuppressive therapy.
REVISTA
/ JOURNAL: - Transplant Proc 2001 May;33(3):2089-91.
AUTORES
/ AUTHORS: - Paul LC
INSTITUCIÓN
/ INSTITUTION: - Department of Nephrology, Leiden
University Medical Center, Leiden, The Netherlands. N. Ref:: 21
----------------------------------------------------
[185]
TÍTULO / TITLE: - Molecular and cellular
mechanisms of donor cell-induced tolerance.
REVISTA
/ JOURNAL: - Immunol Res 2002;26(1-3):119-29.
AUTORES
/ AUTHORS: - George JF; Ahumada L; Lu A
INSTITUCIÓN
/ INSTITUTION: - Department of Surgery, University of
Alabama at Birmingham, 35294-0007, USA. jgeorge@uab.edu
RESUMEN
/ SUMMARY: - The induction of immunologic tolerance to
solid organ allografts is a subject of intense investigation because of the
morbidity and mortality associated with standard immunosuppressive therapy. One
method that is currently in clinical and preclinical testing involves the
transient ablation of recipient T cells using polyclonal antithymocyte sera or
monoclonal anti-CD4/CD8 antibody treatment, followed by the posttransplant
administration of donor bone marrow cells or of donor peripheral lymphoid
populations. Recent studies in our laboratory have shown that the molecular and
cellular basis of the prolongation of graft survival by donor cell
administration depends on the cellular compartment from which the donor cells
were derived. We provide here a brief review of these data followed by new data
suggesting that the mode of peripheral and central selection is also dependent
on the source from which the donor cells were derived. N. Ref:: 38
----------------------------------------------------
[186]
TÍTULO / TITLE: - Cyclosporine-associated
encephalopathy: a case report and literature review.
REVISTA
/ JOURNAL: - Transplant Proc 2001
Nov-Dec;33(7-8):3700-1.
AUTORES
/ AUTHORS: - Chang SH; Lim CS; Low TS; Chong HT; Tan SY
INSTITUCIÓN
/ INSTITUTION: - Renal Unit, Department of Medicine,
University of Malaya Medical Center, Kuala Lumpur, Malaysia.
----------------------------------------------------
[187]
TÍTULO / TITLE: - Diagnosis and
management of refractoriness to platelet transfusion.
REVISTA
/ JOURNAL: - Blood Rev 2001 Dec;15(4):175-80.
●●
Enlace al texto completo (gratuito o de pago) 1054/blre.2001.0164
AUTORES
/ AUTHORS: - Schiffer CA
INSTITUCIÓN
/ INSTITUTION: - Karmanos Cancer Institute, Wayne State
University School of Medicine, Detroit, MI 48201, USA. schiffer@karmanos.org
RESUMEN
/ SUMMARY: - Improvements in the availability and
quality of platelet transfusions have markedly reduced the morbidity and
mortality associated with intensive myelosuppressive therapy. Alloimmunization
and refractoriness to platelet transfusion remains a significant clinical
problem, although the incidence of alloimmunization may be declining due to
more widespread use of leucocyte depleted products. Alloimmunization can be
distinguished from other causes of poor post transfusion increments by the
measurement of lymphocytotoxic or antiplatelet antibodies. In addition to
medical approaches to reduce the risk of bleeding in individual patients,
identification of histocompatible donors can usually be accomplished by HLA
matching of donor and recipient, platelet cross matching or a combination of
both techniques. There are a number of selection strategies which can be
utilized and optimal patient management requires close cooperation and
communication between clinicians and blood centers. N. Ref:: 48
----------------------------------------------------
[188]
TÍTULO / TITLE: - IL-17 as a potential
target for modulating airway neutrophilia.
REVISTA
/ JOURNAL: - Curr Pharm Des 2002;8(20):1855-61.
AUTORES
/ AUTHORS: - Laan M; Linden
INSTITUCIÓN
/ INSTITUTION: - Lung Pharmacology Group, Department of
Respiratory Medicine Allergology, Guldhedsgatan 10A, Gothenburg, SE-413 46,
Sweden. martti.laan@hjl.gu.se
RESUMEN
/ SUMMARY: - Several chronic inflammatory airway
diseases are characterized by an increased number of neutrophils in the
airways. There is evidence that the recruitment of these neutrophils can be
controlled by certain T-lymphocytes. However, the mechanisms behind this T-cell
control of airway neutrophilia are poorly understood. In this review, we
summarize the evidence that interleukin (IL)-17 released from T-lymphocytes of
the CD45RO+ subset can link the activation of these T-cells to the recruitment
and activation of neutrophils. This evidence suggests that
pharmacotherapeutical modulation of neutrophilic airway inflammation can be
achieved using several different strategies, including inhibition of IL-17
production by cAMP elevating agents or certain nuclear factor inhibitors,
neutralization of released IL-17 protein by specific anti-IL-17-antibodies,
blockade of the IL-17 receptor as well as inhibition of certain MAP kinases
mediating the post receptor effects of IL-17 in airway cells. Additional
studies on animals in vivo and patients, respectively, are needed to further
evaluate the pharmacotherapeutical potential of these strategies. N. Ref:: 57
----------------------------------------------------
[189]
TÍTULO / TITLE: - Current immunosuppressant
regimens: considerations for critical care.
REVISTA
/ JOURNAL: - Curr Opin Crit Care 2001 Aug;7(4):242-50.
AUTORES
/ AUTHORS: - Kahan BD; Koch SM
INSTITUCIÓN
/ INSTITUTION: - Division of Immunology and Organ
Transplantation, Department of Surgery, The University of Texas Medical School
at Houston, 6431 Fannin Street, Houston, TX 77030, USA. Barry.D.Kahan@uth.tmc.edu
RESUMEN
/ SUMMARY: - While current immunosuppressive drug
regimens have significantly increased the rate of successful transplantation
outcomes, they convey potentially serious and overlapping adverse effects.
Cyclosporine and tacrolimus are the cornerstones of current immunosuppression,
achieving excellent one-year renal graft survival rates. Other promising new
drugs include sirolimus, which has been demonstrated to reduce efficacy failure
rates among renal transplant recipients, and everolimus, which is currently
undergoing clinical trials. Agents targeting novel sites in the immune response
or disrupting the ischemia-reperfusion cascades are currently under
development. Among them, only FTY720 is undergoing large-scale human clinical
trials. With its unique mechanism of action and synergistic interactions with
cyclosporine and sirolimus, it may provide the foundation for a new era in
immunosuppression. N.
Ref:: 66
----------------------------------------------------
[190]
TÍTULO / TITLE: - Posterior
leukoencephalopathy syndrome.
REVISTA
/ JOURNAL: - Postgrad Med J 2001 Jan;77(903):24-8.
AUTORES
/ AUTHORS: - Garg RK
INSTITUCIÓN
/ INSTITUTION: - Department of Neurology, Institute of
Medical Sciences, Banaras Hindu University, Varanasi, India.
RESUMEN
/ SUMMARY: - Posterior leukoencephalopathy syndrome is
a newly recognised brain disorder that predominantly affects the cerebral white
matter. Oedematous lesions particularly involve the posterior parietal and
occipital lobes, and may spread to basal ganglia, brain stem, and cerebellum.
This rapidly evolving neurological condition is clinically characterised by
headache, nausea and vomiting, seizures, visual disturbances, altered
sensorium, and occasionally focal neurological deficit. Posterior
leukoencephalopathy syndrome is often associated with an abrupt increase in
blood pressure and is usually seen in patients with eclampsia, renal disease,
and hypertensive encephalopathy. It is also seen in the patients treated with
cytotoxic and immunosuppressive drugs such as cyclosporin, tacrolimus, and
interferon alfa. The lesions of posterior leukoencephalopathy are best
visualised with magnetic resonance (MR) imaging. T2 weighted MR images, at the
height of symptoms, characteristically show diffuse hyperintensity selectively
involving the parieto-occipital white matter. Occasionally the lesions also
involve the grey matter. Computed tomography can also be used satisfactorily to
detect hypodense lesions of posterior leukoencephalopathy. Early recognition of
this condition is of paramount importance because prompt control of blood
pressure or withdrawal of immunosuppressive agents will cause reversal of the
syndrome. Delay in the diagnosis and treatment can result in permanent damage
to affected brain tissues. N.
Ref:: 30
----------------------------------------------------
[191]
TÍTULO / TITLE: - Calcineurin phosphatase
activity and immunosuppression. A review on the role of calcineurin phosphatase
activity and the immunosuppressive effect of cyclosporin A and tacrolimus.
REVISTA
/ JOURNAL: - Scand J Immunol 2003 Feb;57(2):93-8.
AUTORES
/ AUTHORS: - Jorgensen KA; Koefoed-Nielsen PB;
Karamperis N
INSTITUCIÓN
/ INSTITUTION: - Research Laboratory, Department of Renal
Medicine C, Skejby Sygehus, Arhus University Hospital, Arhus N, Denmark. kaj@dadlnet.dk
RESUMEN
/ SUMMARY: - The mode of immunosuppressive action of
tacrolimus (FK506) and cyclosporin A has been elucidated. Both drugs bind to
proteins in the cytoplasm to form complexes, which in turn inhibit the
phosphatase activity of calcineurin, an important limiting step in the
activation of T cells. The association between drug uptake (pharmacokinetics)
and enzyme inhibition (pharmacodynamics) is under current investigation. Great
variations in the correlation between blood drug levels and enzyme inhibition could
indicate that monitoring calcineurin phosphatase activity for treatment might
be superior to monitoring blood drug levels.
N. Ref:: 52
----------------------------------------------------
[192]
TÍTULO / TITLE: - Lichen planus
esophagitis: report of three patients treated with oral tacrolimus or
intraesophageal corticosteroid injections or both.
REVISTA
/ JOURNAL: - Dis Esophagus 2003;16(1):47-53.
AUTORES
/ AUTHORS: - Keate RF; Williams JW; Connolly SM
INSTITUCIÓN
/ INSTITUTION: - Division of Gastroenterology and
Hepatology, Mayo Clinic, Scottsdale, AZ 85259, USA. keate.ray@mayo.edu
RESUMEN
/ SUMMARY: - Clinically significant involvement of the
esophagus is uncommon in patients who have lichen planus, a common disorder of
squamous epithelium. In three patients who had oral, cutaneous, and esophageal
lichen planus, endoscopic intralesional esophageal injection of corticosteroids
(in all three patients) and oral tacrolimus (FH506) (in two patients) resulted in
improvement in dysphagia, a less frequent need for dilation, and improvement in
esophageal inflammation. N.
Ref:: 36
----------------------------------------------------
[193]
TÍTULO / TITLE: - Prevention and
treatment of severe hemodynamic compromise in pediatric heart transplant
patients.
REVISTA
/ JOURNAL: - Paediatr Drugs 2002;4(11):705-15.
AUTORES
/ AUTHORS: - Costello JM; Pahl E
INSTITUCIÓN
/ INSTITUTION: - Division of Pulmonary and Critical Care
Medicine, Department of Pediatrics, The Children’s Memorial Hospital, Feinberg
School of Medicine at Northwestern University, Chicago, Illinois 60614, USA.
RESUMEN
/ SUMMARY: - Allograft rejection is a leading cause of
severe hemodynamic compromise in pediatric heart transplant patients. A
triple-drug immunosuppression regimen, which includes a calcineurin inhibitor,
antiproliferative agent, and corticosteroid, suppresses the immune system at
multiple different levels for optimal graft protection while minimizing the
adverse effects of any one particular agent. Some pediatric centers also use
induction therapy with anti-T cell antibodies immediately following
transplantation as additional rejection prophylaxis. These antibodies augment
immunosuppression by either depleting the T cell pool or blocking interleukin-2
receptors on activated T cells. Despite the aggressive preventive measures
outlined above, some pediatric heart transplant patients will develop severe
hemodynamic compromise, most commonly due to fulminant rejection. Such patients
require attention to, and optimization of, the four determinants of cardiac
output (heart rate, preload, contractility and afterload) to stabilize the
circulation until the rejection can be reversed. Careful administration of
volume, diuretics, inotropes, and afterload-reducing agents will meet this
goal. Patients with allograft rejection require augmentation of immune
suppression to facilitate myocardial recovery. Corticosteroids form the
cornerstone of treatment for both cellular and vascular rejection. In patients with
refractory cellular rejection, conversion to mycophenolate mofetil or
tacrolimus may be appropriate if these agents are not already being used for
maintenance immunosuppression. Critically ill patients may additionally benefit
from muromonab-CD3 (OKT3) to augment lympholysis. Treatment employed
specifically for humoral rejection is prescribed with the intention of
suppressing new antibody formation, removing circulating antibody, and
improving coronary blood flow. In addition to corticosteroids, cyclophosphamide
and antithymocyte globulin or muromonab-CD3, along with plasmapheresis, may
improve survival. Systemic heparinization should be considered to minimize
coronary thrombosis in patients with humoral rejection. In the future, novel
immunosuppressive agents may further assist in the prevention as well as
treatment of severe hemodynamic compromise due to rejection in pediatric heart
transplant recipients. N.
Ref:: 99
----------------------------------------------------
[194]
TÍTULO / TITLE: - Anemia in children
after transplantation: etiology and the effect of immunosuppressive therapy on
erythropoiesis.
REVISTA
/ JOURNAL: - Pediatr Transplant 2003 Aug;7(4):253-64.
AUTORES
/ AUTHORS: - Al-Uzri A; Yorgin PD; Kling PJ
INSTITUCIÓN
/ INSTITUTION: - Department of Pediatrics, Section of
Pediatric Nephrology, Oregon Health Sciences University, 707 SW Gaines Road,
Portland, OR, USA. aluzria@ohsu.edu
RESUMEN
/ SUMMARY: - Anemia in children after renal
transplantation is more common than previously appreciated. Multiple factors
appear to play roles in the development of post-transplant anemia, the most
common of which is absolute and/or functional iron deficiency anemia. Most
experts recommend that iron limited anemias in transplant patients should be
diagnosed using the same criteria as for chronic renal failure patients. Serum
erythropoietin (EPO) levels are expected to normalize after a successful renal
transplantation with a normal kidney function, yet both EPO deficiency and
resistance have been reported. While no large controlled trials comparing the
effect of different immunosuppressive agents on erythropoiesis after
transplantation have been performed, generalized bone marrow suppression
attributable to azathioprine (AZA), mycophenolate mofetil (MMF), tacrolimus,
antithymocyte preparations has been reported. Pure red cell aplasia (PRCA)
occurs rarely after transplantation and is characterized by the selective
suppression of erythroid cells in the bone marrow. PRCA has been reported with
the use of AZA, MMF, tacrolimus, angiotensin converting enzyme inhibitors
(ACEI), but not with cyclosporine (CSA) use. Post-transplant hemolytic uremic
syndrome has been reported with orthoclone anti T-cell antibody (OKT3), CSA and
tacrolimus therapy. Viral infections including cytomegalovirus, Epstein-Barr
virus and human parvovirus B19 have been reported to cause generalized marrow
suppression. Management of severe anemia associated with immunosuppressive
drugs generally requires lowering the dose, drug substitution or, when
possible, discontinuation of the drug. Because this topic has been incompletely
studied, our recommendation as to the best immunosuppressive protocol after
renal transplantation remains largely dependent on the clinical response of the
individual patient. N.
Ref:: 86
----------------------------------------------------
[195]
TÍTULO / TITLE: - The state of the art in
the management of inflammatory bowel disease.
REVISTA
/ JOURNAL: - Rev Gastroenterol Disord 2003
Spring;3(2):81-92.
AUTORES
/ AUTHORS: - Hanauer SB; Present DH
INSTITUCIÓN
/ INSTITUTION: - Section of Gastroenterology and Nutrition,
University of Chicago, Pritzker School of Medicine, Chicago, IL, USA.
RESUMEN
/ SUMMARY: - Ulcerative colitis (UC) and Crohn’s
disease (CD), collectively known as inflammatory bowel disease (IBD), afflict
an estimated one million Americans and produce symptoms that impair quality of
life and ability to function. Progress in IBD management strategies has led to
optimized approaches for achieving the two primary clinical goals of therapy:
induction and maintenance of remission. Although surgery is indicated to treat
refractory disease or specific complications, pharmacotherapy is the
cornerstone of IBD management. The efficacy of aminosalicylates for induction
of remission in mild to moderate UC and CD is well established, as is their
role for maintenance of remission in UC. The sulfa-free mesalamine formulation
offers an adverse effect profile similar to that of placebo, enabling the
administration of higher, more effective doses. Although corticosteroids
provide potent anti-inflammatory effects, their benefits are countermanded by
the risk of intolerable and serious adverse effects, and they are ineffective
for maintenance therapy. Other agents effective in inducing or maintaining
remission are azathioprine, 6-mercaptopurine, infliximab, cyclosporine,
methotrexate, and antibiotics. Ongoing clinical trials of experimental
therapies will generate new tools for IBD treatment. Currently, a broad range
of options allows physicians to tailor treatment to each patient’s needs and
preferences. Such considerations are essential for maximizing adherence to
therapy. N. Ref:: 62
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[196]
TÍTULO / TITLE: - Pharmacotherapeutic
management of pulmonary sarcoidosis.
REVISTA
/ JOURNAL: - Am J Respir Med 2003;2(4):311-20.
AUTORES
/ AUTHORS: - Fazzi P
INSTITUCIÓN
/ INSTITUTION: - Cardiac and Thoracic Department,
Respiratory Pathophysiology Section, University of Pisa, Pisa, Italy. pfazzi@dcap.med.unipi.it
RESUMEN
/ SUMMARY: - Corticosteroids are the mainstay of
treatment for sarcoidosis. Although the indications for medical therapy of
sarcoidosis are controversial, standard therapy for symptomatic, progressive
disease consists of corticosteroids. The British Thoracic Society concluded,
with respect to systemic corticosteroids for the treatment of sarcoidosis, that
some patients required no treatment, some required prednisone for control of
symptoms, and others, with persistent disease, appeared to benefit from
long-term corticosteroid therapy. Inhaled budesonide can be an effective
treatment for lung sarcoidosis, with few adverse effects, when used in
combination with oral systemic corticosteroids such as deflazacort administered
in a tapered regimen for 6 months. A randomized controlled trial has also
demonstrated the efficacy of 3 months of treatment with oral prednisolone in a
tapered regimen followed by inhaled budesonide for 15 months in patients with
early stage pulmonary sarcoidosis.Alternative drugs are required in chronic
resistant sarcoidosis and/or in conditions where systemic corticosteroids are
contraindicated. Immunosuppressive agents (chlorambucil, cyclophosphamide,
methotrexate, cyclosporine, azathioprine), anticytokine agents (thalidomide,
pentoxifylline), antimalarials (chloroquine, hydroxychloroquine), melatonin and
monoclonal antibody (infliximab) have been used in such situations.Chlorambucil
and cyclophosphamide have been used in anecdotal cases of pulmonary sarcoidosis
as corticosteroid-sparing agents. However, their toxicity and neoplastic
potential recommend prudence in patient selection. A comparison between
combination therapy with cyclosporine and prednisone and prednisone alone has
shown an increased prevalence of serious adverse effects with combined therapy
with no between-group differences in treatment efficacy. The cost and toxicity
of cyclosporine limit its use to patients in whom its efficacy has been
proven.In patients with chronic or refractory disease, methotrexate, usually
administered once a week as a single oral dose for at least 2 years, has
resulted in a significant improvement in respiratory function, chest
radiographs and extrapulmonary manifestations. In most patients, this treatment
enabled discontinuation of corticosteroids.Azathioprine may be effective as a
corticosteroid-sparing agent in the long-term treatment of sarcoidosis. The
combination of prednisolone and azathioprine over a period of 2 years has
induced long-lasting remission in patients with resistant sarcoidosis.
Thalidomide at low doses is effective in selected cases of sarcoidosis with
cutaneous and mild pulmonary involvement. Pentoxifylline alone or combined with
low doses of corticosteroids has achieved significant improvement in
respiratory function in patients with pulmonary sarcoidosis. Chloroquine and
hydroxychloroquine have been shown to have a specific effect in cutaneous
manifestations, neurological involvement and hypercalcemia associated with
sarcoidosis. Infliximab has yielded good results in patients with chronic
resistant pulmonary and extrapulmonary sarcoidosis resistant to corticosteroid
and cytotoxic therapy. The effectiveness of melatonin in cutaneous and
pulmonary sarcoidosis has also been confirmed in a single center. N. Ref:: 52
----------------------------------------------------
[197]
TÍTULO / TITLE: - The molecular target of
rapamycin (mTOR) as a therapeutic target against cancer.
REVISTA
/ JOURNAL: - Cancer Biol Ther 2003 Jul-Aug;2(4 Suppl
1):S169-77.
AUTORES
/ AUTHORS: - Mita MM; Mita A; Rowinsky EK
INSTITUCIÓN
/ INSTITUTION: - Institute for Drug Development; Cancer
Therapy and Research Center; San Antonio, Texas 78229, USA. mmita@saci.org
RESUMEN
/ SUMMARY: - The molecular target of rapamycin (mTOR),
which is a member of the phosphoinositide 3-kinase related kinase (PIKK) family
and a central modulator of cell growth, is a prime strategic target for
anti-cancer therapeutic development. mTOR plays a critical role in transducing
proliferative signals mediated through the phosphatidylinositol 3 kinase
(PI3K)/protein kinase B (Akt) signaling pathway, principally by activating downstream
protein kinases that are required for both ribosomal biosynthesis and
translation of key mRNAs of proteins required for G(1) to S phase traverse. By
targeting mTOR, the immunsuppressant and antiproliferative agent rapamycin
(RAP) inhibits signals required for cell cycle progression, cell growth, and
proliferation. RAP, a complex macrolide and highly potent fungicide,
immunosuppressant, and anti-cancer agent, is a highly specific inhibitor of
mTOR. In essence, RAP gains function by binding to the immunophilin FK506
binding protein 12 (FKBP12) and the resultant complex inhibits the activity of
mTOR. Since mTOR activates both the 40S ribosomal protein S6 kinase
((p)70(s6k)) and the eukaryotic initiation factor 4E-binding protein-1
(4E-BP1), RAP blocks activation of these downstream signaling elements, which
results in cell cycle arrest in the G1 arrest. RAP also prevents
cyclin-dependent kinase (cdk) activation, inhibits retinoblastoma protein
((p)Rb) phosphorylation, and accelerates the turnover of cyclin D1 that leads
to a deficienciy of active cdk4/cyclin D1 complexes, all of which potentially
contribute to the prominent inhibitory effects of RAP at the G(1)/S phase
transition. Both RAP and several RAP analogs with more favorable pharmaceutical
properties have demonstrated prominent growth inhibitory effects against a
broad range of human cancers in both preclinical and early clinical
evaluations. This review will summarize the principal mechanisms of action of
RAP and RAP derivatives and their potential utility of these agents as
anti-cancer therapeutics. The preliminary results of early clinical evaluations
with RAP analogs and the unique developmental challenges that lie ahead will
also be discussed. N.
Ref:: 112
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[198]
TÍTULO / TITLE: - Combination treatment
in autoimmune diseases: systemic lupus erythematosus.
REVISTA
/ JOURNAL: - Springer Semin Immunopathol
2001;23(1-2):75-89.
AUTORES
/ AUTHORS: - Moroni G; Della Casa Alberighi O;
Ponticelli C
INSTITUCIÓN
/ INSTITUTION: - Divisione di Nefrologia e Dialisi,
Ospedale Maggiore IRCCS, Via della Commenda 15, 20122 Milan, Italy. N. Ref:: 84
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[199]
TÍTULO / TITLE: - Influence of one human
leukocyte antigen mismatch on outcome of allogeneic bone marrow transplantation
from related donors.
REVISTA
/ JOURNAL: - Hematology 2003 Feb;8(1):27-33.
●●
Enlace al texto completo (gratuito o de pago) 1080/1024533031000072054
AUTORES
/ AUTHORS: - Hasegawa W; Lipton JH; Messner HA; Jamal
H; Yi QL; Daly AS; Kotchetkova N; Kiss TL
INSTITUCIÓN
/ INSTITUTION: - Bone Marrow Transplant Service, Princess
Margaret Hospital/University Health Network, Toronto, Ont, M5G 2M9, Canada.
RESUMEN
/ SUMMARY: - This study compares the clinical outcomes
of 60 consecutive patients who received an allogeneic blood or marrow stem cell
transplant (BMT) from one Human Leukocyte Antigen (HLA) mismatched related
donors with those of 120 matched patients who had HLA identical sibling donors.
The control patients were matched for diagnosis, disease status, conditioning regimen,
and age at BMT. All patients received standard CYA and MTX for GVHD
prophylaxis. The probability of overall survival (OS) at 5 years was 35% in the
study group compared to 56% in the control group. The relapse rates and acute
GVHD rates did not differ between the two groups. Graft failure was a
significant problem in the study group compared to the control group (13 vs.
0%, p < 0.0001). All cases of graft failure occurred in patients with a
mismatch in the host-versus-graft direction. BMT-related deaths were also
increased in the study group. Forty percent of deaths were caused by infection
in the study group vs. 19% in the control group (p < 0.01). In conclusion,
the OS of patients receiving marrow/stem cells from one antigen mismatched
related donors was inferior to that of controls with HLA-identical related
donors. There was an increase in mortality related to infections occurring in
the setting of an increased frequency of graft failure in these patients. N. Ref:: 21
----------------------------------------------------
[200]
TÍTULO / TITLE: - Apoptosis, TGF beta and
transfusion-related immunosuppression: Biologic versus clinical effects.
REVISTA
/ JOURNAL: - Transfus Apheresis Sci 2003
Oct;29(2):127-9.
AUTORES
/ AUTHORS: - Dzik WH
INSTITUCIÓN
/ INSTITUTION: - Blood Transfusion Service, J-224,
Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA. sdzik@partners.org
RESUMEN
/ SUMMARY: - Whether or not blood transfusion exerts an
immunosuppressive effect on the recipient remains an area of controversy. The
mechanism to clearly explain the effect has been elusive. We have previously
suggested that there may be two categories of immunosuppressive transfusion
effect: one which is HLA-dependent and directed against adaptive immunity and a
second category which is mild, non-specific, and directed against innate
immunity. This non-specific effect might result from the infusion of apoptotic
blood cells. There is solid evidence that blood cells undergo apoptotic changes
during refrigerated storage. The infusion of apoptotic cells has recently been
shown in animal models to be immunosuppressive. Immunosuppression resulting
from the infusion of apoptotic cells may be linked to transforming growth factor
beta (TGF-beta). N.
Ref:: 10
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