#11#
Revisiones-Ciencias
Básicas-Eventos celulares *** Reviews-Basic Sciences-Cellular events
AGENTES
INMUNOSUPRESORES *** IMMUNOSUPPRESSIVE COMPOUNDS
(Conceptos
/ Keywords: Immunosuppressive comp; Muromonab-cd3; Sirolimus; Tacrolimus;
Cyclosporine; Mycophenolic acid; Antilymphocyte serum; Immunosuppressive comp.
used in oncology, etc).
Enero /
January 2001 --- Marzo / March 2004
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Only articles written in Spanish and/or English are included.
[1]
TÍTULO / TITLE: - Integration of growth
factor and nutrient signaling: implications for cancer biology.
REVISTA
/ JOURNAL: - Mol Cell 2003 Aug;12(2):271-80.
AUTORES
/ AUTHORS: - Shamji AF; Nghiem P; Schreiber SL
INSTITUCIÓN
/ INSTITUTION: - Harvard Biophysics Program, Harvard
University, 12 Oxford Street, Cambridge, MA 02138, USA.
RESUMEN
/ SUMMARY: - Signaling networks that promote cell
growth are frequently dysregulated in cancer. One regulatory network, which
converges on effectors such as 4EBP1 and S6K1, leads to growth by promoting
protein synthesis. Here, we discuss how this network is regulated by both
extracellular signals, such as growth factors, and intracellular signals, such
as nutrients. We discuss how mutations amplifying either type of signal can
lead to tumor formation. In particular, we focus on the recent discovery that a
tumor suppressor complex whose function is lost in tuberous sclerosis patients
regulates the nutrient signal carried by the critical signaling protein TOR to
the effectors 4EBP1 and S6K1. Finally, we describe how the small molecule
rapamycin, which inhibits TOR and thereby the activation of these effectors,
could be useful to treat tumors that have become dependent upon this pathway
for growth. N. Ref:: 80
----------------------------------------------------
[2]
TÍTULO / TITLE: - Dendritic cells:
emerging pharmacological targets of immunosuppressive drugs.
REVISTA
/ JOURNAL: - Nat Rev Immunol 2004 Jan;4(1):24-34.
●●
Enlace al texto completo (gratuito o de pago) 1038/nri1256
AUTORES
/ AUTHORS: - Hackstein H; Thomson AW
INSTITUCIÓN
/ INSTITUTION: - Institute for Clinical Immunology and
Transfusion Medicine, Justus-Liebig University Giessen, Langhansstr. 7, D-35392
Giessen, Germany. holger.hackstein@immunologie.med.uni-giessen.de
RESUMEN
/ SUMMARY: - Immunosuppressive drugs have
revolutionized organ transplantation and improved the therapeutic management of
autoimmune diseases. The development of immunosuppressive drugs and
understanding of their action traditionally has been focused on lymphocytes,
but recent evidence indicates that these agents interfere with immune responses
at the earliest stage, targeting key functions of dendritic cells (DCs). Here,
we review our present understanding of how classical and new immunosuppressive
agents interfere with DC development and function. This knowledge might provide
a rational basis for the selection of immunosuppressive drugs in different
clinical settings and for the generation of tolerogenic DCs in the
laboratory. N. Ref:: 116
----------------------------------------------------
[3]
- Castellano -
TÍTULO / TITLE:La ruta de senalizacion
CA++/calcineurina/NFAT en activacion endotelial y angiogenesis: efectos de la
ciclosporina A. CA++/ calcineurin/NFAT signaling in endothelial activation and
angiogenesis: effects od cyclosporin A .
REVISTA
/ JOURNAL: - Nefrologia. Acceso gratuito al texto
completo.
●●
Enlace a la Editora de la Revista http://www.aulamedica.es/nefrologia/
●●
Cita: Nefrologia: <> 2003;23 Suppl 3:44-8.
AUTORES
/ AUTHORS: - Quesada AJ; Redondo JM
INSTITUCIÓN
/ INSTITUTION: - Centro de Biologia Molecular Severo Ochoa,
Consejo Superior de Investigaciones Cientificas, Universidad Autonoma de Madrid
y Centro Nacional de Investigaciones Cardiovasculares (CNIC), Sinesio Delgado,
4 28049 Cantoblanco, Madrid. jmredondo@cbm.uam.es N. Ref:: 31
----------------------------------------------------
[4]
TÍTULO / TITLE: - Identification of TOR
signaling complexes: more TORC for the cell growth engine.
REVISTA
/ JOURNAL: - Cell 2002 Oct 4;111(1):9-12.
AUTORES
/ AUTHORS: - Abraham RT
INSTITUCIÓN
/ INSTITUTION: - Program in Signal Transduction Research,
Cancer Research Center, The Burnham Institute, 10901 North Torrey Pines Road,
La Jolla, CA 92037, USA. abraham@burnham.org
RESUMEN
/ SUMMARY: - The Target of Rapamycin (TOR) proteins
function in signaling pathways that promote protein synthesis and cell growth.
In yeast, TOR signaling is regulated by nutrient availability, whereas in
metazoan cells TOR activities may be controlled by both nutrients and growth
factors. The recent identification of novel TOR-interacting proteins has
provided crucial insights into TOR regulation and function. N. Ref:: 20
----------------------------------------------------
[5]
TÍTULO / TITLE: - Interleukin-2 receptor
monoclonal antibodies in renal transplantation: meta-analysis of randomised
trials.
REVISTA
/ JOURNAL: - British Medical J (BMJ). Acceso gratuito
al texto completo.
●●
Enlace a la Editora de la Revista http://bmj.com/search.dtl
●●
Cita: British Medical J. (BMJ): <> 2003 Apr 12;326(7393):789.
●●
Enlace al texto completo (gratuito o de pago) 1136/bmj.326.7393.789
AUTORES
/ AUTHORS: - Adu D; Cockwell P; Ives NJ; Shaw J;
Wheatley K
INSTITUCIÓN
/ INSTITUTION: - Department of Nephrology, Queen Elizabeth
Hospital, Birmingham, B15 2TH. dwomoa.adu@uhb.nhs.uk
RESUMEN
/ SUMMARY: - OBJECTIVE: To study the effect of
interleukin-2 receptor monoclonal antibodies on acute rejection episodes, graft
loss, deaths, and rate of infection and malignancy in patients with renal
transplants. DESIGN: Meta-analysis of published data. DATA SOURCES: Medline,
Embase, and Cochrane library for years 1996-2003 plus search of medical
editors’ trial amnesty and contact with manufacturers of the antibodies.
SELECTION OF STUDIES: Randomised controlled trials comparing interleukin-2
receptor antibodies with placebo or no additional treatment in patients with
renal transplants receiving ciclosporin based immunosuppression. RESULTS: Eight
randomised controlled trials involving 1871 patients met the selection criteria
(although only 1858 patients were analysed). Interleukin-2 receptor antibodies
significantly reduced the risk of acute rejection (odds ratio 0.51, 95%
confidence interval 0.42 to 0.63). There were no significant differences in the
rate of graft loss (0.78, 0.58 to 1.04), mortality (0.75, 0.46 to 1.23),
overall incidence of infections (0.97, 0.77 to 1.24), incidence of
cytomegalovirus infections (0.81, 0.62 to 1.04), or risk of malignancies at one
year (0.82, 0.39 to 1.70). The different antibodies had a similar sized effect
on acute rejection (test for heterogeneity P=0.7): anti-Tac (0.37, 0.16 to
0.89), BT563 (0.37, 0.1 to 1.38), basiliximab (0.56, 0.44 to 0.72), and
daclizumab (0.46, 0.32 to 0.67). The reduction in acute rejections was similar
for all ciclosporin based immunosuppression regimens (test for heterogeneity
P=1.0). CONCLUSIONS: Adding interleukin-2 receptor antibodies to ciclosporin
based immunosuppression reduces episodes of acute rejection at six months by
49%. There is no evidence of an increased risk of infective complications.
Longer follow up studies are needed to confirm whether interleukin-2 receptor
antibodies improve long term graft and patient survival.
----------------------------------------------------
[6]
TÍTULO / TITLE: - Novel therapeutic
molecular targets for prostate cancer: the mTOR signaling pathway and epidermal
growth factor receptor.
REVISTA
/ JOURNAL: - J Urol 2004 Feb;171(2 Pt 2):S41-3;
discussion S44.
●●
Enlace al texto completo (gratuito o de pago) 1097/01.ju.0000108100.53239.b7
AUTORES
/ AUTHORS: - Tolcher AW
INSTITUCIÓN
/ INSTITUTION: - Director Clinical Research, Institute for
Drug Development Cancer Therapy and Research Center, San Antonio, Texas, USA.
RESUMEN
/ SUMMARY: - PURPOSE: The scientific rationale and
existing evidence for the use of novel molecular targets in the chemoprevention
of cancer are reviewed, with special attention to prostate cancer. MATERIALS
AND METHODS: A search for relevant literature on basic science and clinical
trials was conducted using PubMed/MEDLINE. RESULTS: The emergence of
molecularly targeted therapies for advanced malignancies creates an important
opportunity to examine these agents for the chemoprevention of prostate cancer.
Two critical targets in the proliferation and malignant transformation of
normal cells, the PI3/Akt signal transduction pathway and the epidermal growth
factor receptor, are currently the focus of several novel investigational
therapies that are in late stage phase II and phase III studies. CONCLUSIONS:
Research to date supports consideration of these novel molecular targets as
future agents in the chemoprevention of prostate cancer. N. Ref:: 28
----------------------------------------------------
[7]
TÍTULO / TITLE: - 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: - The transplantation of
hematopoietic stem cells after non-myeloablative conditioning: a cellular
therapeutic approach to hematologic and genetic diseases.
REVISTA
/ JOURNAL: - Immunol Res 2003;28(1):13-24.
AUTORES
/ AUTHORS: - Maris M; Storb R
INSTITUCIÓN
/ INSTITUTION: - Fred Hutchinson Cancer Research Center,
and University of Washington, Seattle, WA, USA. mmaris@fhcrc.org
RESUMEN
/ SUMMARY: - Originally, allogeneic hematopoietic stem
cell transplantation (HSCT) was viewed as a form of rescue from the marrow
lethal effects of high doses of chemo-radiotherapy used to both eradicate
malignancy and to provide sufficient immunosuppression to ensure allogeneic
engraftment. Clear evidence of a therapeutic graft-versus-tumor (GVT) effect
mediated by allogeneic effector cells (T cells) has prompted the exploration of
HSCT regimens that rely solely upon host immunosuppression (non-myeloablative)
to facilitate allogeneic donor engraftment. The engrafted donor effector cells
are then used to accomplish the task of eradicating host malignant cells. The
non-myeloblative regimen developed in Seattle uses 2 Gy total body irradiation
(TBI) before transplant followed by postgrafting cyclosporine (CSP) and
mycophenolate mofetil (MMF). This regimen resulted in initial mixed donor-host
chimerism in all patients with hematologic malignancies and genetic disorders
who received HLA-matched sibling allografts. The 17% incidence of graft
rejection was reduced to 3% with the addition of fludarabine, 30 mg/m2/day on d
-4, -3, and -2. The non-myeloablative combination of fludarabine/TBI has also
been successful at achieving high engraftment rates in recipients of 10 of 10
HLA antigen matched unrelated donor HSCTs in patients with hematologic
malignancies. By reducing acute toxicities relative to conventional HSCT, most
patients have received their pre- and post-HSCT therapy almost exclusively as
outpatients. Acute and chronic GVHD occur after non-myeloablative HSCT, but the
incidence and severity appear less compared to conventional HSCT. As in
conventional transplants, immune dysregulation from GVHD and its treatment and
delayed reconstitution of immune function continue to present risks to patients
who have otherwise undergone successful non-myeloablative HSCT. Cellular
therapeutic effects have been observed after non-myeloablative HSCT such as
correction of inherited genetic disorders, and eradication of hematologic
malignant diseases and renal cell carcinoma via GVT responses. N. Ref:: 52
----------------------------------------------------
[10]
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
----------------------------------------------------
[11]
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
----------------------------------------------------
[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: - 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
----------------------------------------------------
[14]
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
----------------------------------------------------
[15]
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.
----------------------------------------------------
[16]
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.
----------------------------------------------------
[17]
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
----------------------------------------------------
[18]
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.
----------------------------------------------------
[19]
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
----------------------------------------------------
[20]
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
----------------------------------------------------
[21]
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
----------------------------------------------------
[22]
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
----------------------------------------------------
[23]
- 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
----------------------------------------------------
[24]
TÍTULO / TITLE: - Immunoablation followed
or not by hematopoietic stem cells as an intense therapy for severe autoimmune
diseases. New perspectives, new problems.
REVISTA
/ JOURNAL: - Haematologica. Acceso gratuito al texto
completo.
●●
Enlace a la Editora de la Revista http://db.doyma.es/
●●
Cita: Haematologica: <> 2001 Apr;86(4):337-45.
AUTORES
/ AUTHORS: - Marmont AM N. Ref:: 127
----------------------------------------------------
[25]
TÍTULO / TITLE: - Protein phosphatase 2A
on track for nutrient-induced signalling in yeast.
REVISTA
/ JOURNAL: - Mol Microbiol. Acceso gratuito al texto
completo a partir de los 2 años de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.blackwell-synergy.com/
●●
Cita: Molecular Microbiology: <> 2002 Feb;43(4):835-42.
AUTORES
/ AUTHORS: - Zabrocki P; Van Hoof C; Goris J; Thevelein
JM; Winderickx J; Wera S
INSTITUCIÓN
/ INSTITUTION: - Laboratorium voor Moleculaire Celbiologie,
K.U.Leuven, Kasteelpark Arenberg 31, B-3001 Leuven-Heverlee, Flanders, Belgium.
RESUMEN
/ SUMMARY: - Early studies identified two bona fide
protein phosphatase 2A (PP2A)-encoding genes in Saccharomyces cerevisiae,
designated PPH21 and PPH22. In addition, three PP2A-related phosphatases,
encoded by PPH3, SIT4 and PPG1, have been identified. All share as much as 86%
sequence similarity at the amino acid level. This review will focus primarily
on Pph21 and Pph22, but some aspects of Sit4 regulation will also be discussed.
Whereas a role for PP2A in yeast morphology and cell cycle has been readily
recognized, uncovering its function in yeast signal transduction is a more
recent breakthrough. Via their interaction with phosphorylated Tap42, PP2A and
Sit4 play a pivotal role in target of rapamycin (TOR) signalling. PPH22
overexpression mimics overactive cAMP-PKA (protein kinase A) signalling and
PP2A and Sit4 might represent ceramide signalling targets. The methylation of
its catalytic subunit stabilizes the heterotrimeric form of PP2A and might
counteract TOR signalling. We will show how these new elements could lead us to
understand the role and regulation of PP2A in nutrient-induced signalling in
baker’s yeast. N.
Ref:: 41
----------------------------------------------------
[26]
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
----------------------------------------------------
[27]
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
----------------------------------------------------
[28]
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
----------------------------------------------------
[29]
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
----------------------------------------------------
[30]
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
----------------------------------------------------
[31]
TÍTULO / TITLE: - Potassium channels in T
lymphocytes: toxins to therapeutic immunosuppressants.
REVISTA
/ JOURNAL: - Toxicon 2001 Sep;39(9):1269-76.
AUTORES
/ AUTHORS: - George Chandy K; Cahalan M; Pennington M;
Norton RS; Wulff H; Gutman GA
INSTITUCIÓN
/ INSTITUTION: - Department of Physiology and Biophysics,
University of California Irvine, Room 291, John Irvine Smith Hall, Medical
School, Irvine, CA92697, USA. gchandy@uci.edu N. Ref:: 60
----------------------------------------------------
[32]
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
----------------------------------------------------
[33]
TÍTULO / TITLE: - Hepatitis C virus
infection and vasculitis: implications of antiviral and immunosuppressive
therapies.
REVISTA
/ JOURNAL: - Arthritis Rheum 2002 Mar;46(3):585-97.
●●
Enlace al texto completo (gratuito o de pago) 1002/art.10107 [pii
●●
Enlace al texto completo (gratuito o de pago) 1002/art.10107
AUTORES
/ AUTHORS: - Vassilopoulos D; Calabrese LH
INSTITUCIÓN
/ INSTITUTION: - Hippokration General Hospital, Athens
University, Athens, Greece. N.
Ref:: 92
----------------------------------------------------
[34]
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
----------------------------------------------------
[35]
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
----------------------------------------------------
[36]
TÍTULO / TITLE: - A novel pathway
regulating the mammalian target of rapamycin (mTOR) signaling.
REVISTA
/ JOURNAL: - Biochem Pharmacol 2002 Oct 1;64(7):1071-7.
AUTORES
/ AUTHORS: - Chen J; Fang Y
INSTITUCIÓN
/ INSTITUTION: - Department of Cell and Structural Biology,
University of Illinois at Urbana-Champaign, 601 South Goodwin Avenue, B107,
Urbana, IL 61801, USA. jiechen@uiuc.edu
RESUMEN
/ SUMMARY: - Originally discovered as an anti-fungal
agent, the bacterial macrolide rapamycin is a potent immunosuppressant and a
promising anti-cancer drug. In complex with its cellular receptor, the
FK506-binding protein (FKBP12), rapamycin binds and inhibits the function of
the mammalian target of rapamycin (mTOR). By mediating amino acid sufficiency,
mTOR governs signaling to translational regulation and other cellular functions
by converging with the phosphatidylinositol 3-kinase (PI3K) pathway on
downstream effectors. Whether mTOR receives mitogenic signals in addition to
nutrient-sensing has been an unresolved issue, and the mechanism of action of
rapamycin remained unknown. Our recent findings have revealed a novel link
between mitogenic signals and mTOR via the lipid second messenger phosphatidic
acid (PA), and suggested a role for mTOR in the integration of nutrient and
mitogen signals. A molecular mechanism for rapamycin inhibition of mTOR
signaling is proposed, in which a putative interaction between PA and mTOR is
abolished by rapamycin binding. Collective evidence further implicates the
regulation of the rapamycin-sensitive signaling circuitry by phospholipase D,
and potentially by other upstream regulators such as the conventional protein
kinase C, the Rho and ARF families of small G proteins, and calcium ions. As
the mTOR pathway has been demonstrated to be an important anti-cancer target,
the identification of new components and novel regulatory modes in mTOR
signaling will facilitate the future development of diagnostic and therapeutic
strategies. N. Ref:: 67
----------------------------------------------------
[37]
TÍTULO / TITLE: - FTY720: altered
lymphocyte traffic results in allograft protection.
REVISTA
/ JOURNAL: - Transplantation 2001 Sep 15;72(5):764-9.
AUTORES
/ AUTHORS: - Brinkmann V; Pinschewer DD; Feng L; Chen S
INSTITUCIÓN
/ INSTITUTION: - Novartis Pharma AG, Transplantation
Research, WSJ-386.1.01, CH-4002 Basel, Switzerland. N. Ref:: 52
----------------------------------------------------
[38]
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
----------------------------------------------------
[39]
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
----------------------------------------------------
[40]
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
----------------------------------------------------
[41]
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
----------------------------------------------------
[42]
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
----------------------------------------------------
[43]
TÍTULO / TITLE: - Regulation of
translation via TOR signaling: insights from Drosophila melanogaster.
REVISTA
/ JOURNAL: - J Nutr. Acceso gratuito al texto completo
a partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.nutrition.org/
●●
Cita: Journal of Nutrition: <> 2001 Nov;131(11):2988S-93S.
AUTORES
/ AUTHORS: - Miron M; Sonenberg N
INSTITUCIÓN
/ INSTITUTION: - Department of Biochemistry and McGill
Cancer Center, McGill University, Montreal, Quebec, Canada.
RESUMEN
/ SUMMARY: - The target of rapamycin (TOR) proteins are
large protein kinases evolutionarily conserved from yeast to human. A large
body of evidence demonstrates that TOR proteins function in a nutrient-sensing
checkpoint whose role is to restrict growth under conditions of low nutrient
availability. Under such conditions, TOR blocks the transmission of growth-promoting
signals from extracellular stimuli. Recent data obtained by genetic studies in
the fruit fly Drosophila melanogaster demonstrate the importance of both
insulin-like signaling and TOR signaling in promoting growth. Importantly,
these studies identified a major downstream target of TOR and insulin-like
signaling as the translational machinery.
N. Ref:: 63
----------------------------------------------------
[44]
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
----------------------------------------------------
[45]
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
----------------------------------------------------
[46]
TÍTULO / TITLE: - Mechanisms and
consequences of arterial hypertension after renal transplantation.
REVISTA
/ JOURNAL: - Transplantation 2001 Sep 27;72(6
Suppl):S9-12.
AUTORES
/ AUTHORS: - Koomans HA; Ligtenberg G
INSTITUCIÓN
/ INSTITUTION: - Department of Nephrology and Hypertension,
University Hospital Utrecht, The Netherlands. h.a.koomans@digd.azu.nl
RESUMEN
/ SUMMARY: - The high incidence of hypertension after
renal transplantation contributes to the risk of cardiovascular morbidity and
mortality in renal transplant recipients. Although cyclosporine has been
influential in the improvement of transplant outcome, it has emerged as a major
cause of hypertension after organ transplantation. The underlying
pathophysiological mechanisms of cyclosporine-induced hypertension include
enhanced sympathetic nervous system activity, renal vasoconstriction, and
sodium/water retention. Hypertension is also significantly associated with
reduced graft survival and thereby requires aggressive treatment intervention.
Calcium channel blockers may offer some advantages over angiotensin-converting
enzyme inhibitors for the treatment of hypertension in stable renal transplant
recipients. Nevertheless, selection of the most appropriate antihypertensive
agent should take into account the possibility of pharmacokinetic interactions
with immunosuppressive agents. There is evidence to suggest that the use of tacrolimus-based
immunosuppression induces less hypertension compared with cyclosporine. Not
only do patients receiving tacrolimus tend to require less antihypertensive
therapy, but converting patients from cyclosporine to tacrolimus has been shown
to result in significant reductions in blood pressure. Thus, tacrolimus may be
associated with an improved cardiovascular risk profile in renal transplant
recipients. N. Ref:: 26
----------------------------------------------------
[47]
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
----------------------------------------------------
[48]
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
----------------------------------------------------
[49]
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
----------------------------------------------------
[50]
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
----------------------------------------------------
[51]
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.
----------------------------------------------------
[52]
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.
----------------------------------------------------
[53]
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
----------------------------------------------------
[54]
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
----------------------------------------------------
[55]
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
----------------------------------------------------
[56]
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
----------------------------------------------------
[57]
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
----------------------------------------------------
[58]
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
----------------------------------------------------
[59]
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
----------------------------------------------------
[60]
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
----------------------------------------------------
[61]
TÍTULO / TITLE: - Calcineurin phosphatase
in signal transduction: lessons from fission yeast.
REVISTA
/ JOURNAL: - Genes Cells 2002 Jul;7(7):619-27.
AUTORES
/ AUTHORS: - Sugiura R; Sio SO; Shuntoh H; Kuno T
INSTITUCIÓN
/ INSTITUTION: - Division of Molecular Pharmacology and Pharmacogenomics,
Department of Genome Sciences, Kobe University Graduate School of Medicine,
Kobe 650-0017, Japan.
RESUMEN
/ SUMMARY: - Calcineurin (protein phosphatase 2B), the
only serine/threonine phosphatase under the control of Ca2+/calmodulin, is an
important mediator in signal transmission, connecting the Ca2+-dependent
signalling to a wide variety of cellular responses. Furthermore, calcineurin is
specifically inhibited by the immunosuppressant drugs cyclosporin A and
tacrolimus (FK506), and these drugs have been a powerful tool for identifying
many of the roles of calcineurin. Calcineurin is enriched in the neural
tissues, and also distributes broadly in other tissues. The structure of the
protein is highly conserved from yeast to man. The combined use of powerful
genetics and of specific calcineurin inhibitors in fission yeast
Schizosaccharomyces pombe (S. pombe) identified new components of the
calcineurin pathway, and defined new roles of calcineurin in the regulation of
the many cellular processes. Recent data has revealed functional interactions
in which calcineurin phosphatase is involved, such as the cross-talk between
the Pmk1 MAP kinase signalling, or the PI signalling. Calcineurin also
participates in membrane traffic and cytokinesis of fission yeast through its
functional connection with members of the small GTPase Rab/Ypt family, and Type
II myosin, respectively. These findings highlight the potential of fission
yeast genetic studies to elucidate conserved elements of signal transduction cascades. N. Ref:: 51
----------------------------------------------------
[62]
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
----------------------------------------------------
[63]
TÍTULO / TITLE: - Transplantation:
toxicokinetics and mechanisms of toxicity of cyclosporine and macrolides.
REVISTA
/ JOURNAL: - Curr Opin Investig Drugs 2003
Nov;4(11):1287-96.
AUTORES
/ AUTHORS: - Serkova N; Christians U
INSTITUCIÓN
/ INSTITUTION: - Department of Anesthesiology, Clinical
Research & Development, University of Colorado Health Sciences Center, 4200
East Ninth Ave, Room UH-2122, Campus Box B113, Denver, CO 80262, USA.
RESUMEN
/ SUMMARY: - For over two decades, calcineurin
inhibitors (CIs) have been the mainstay of immunosuppressive therapy following
solid-organ transplantation. However, CI nephrotoxicity is one of the main
contributors to chronic kidney allograft dysfunction. A novel class of
immunosuppressants that inhibit the kinase mammalian target of rapamycin
(mTOR), although not nephrotoxic themselves, enhance CI nephrotoxicity. The
biochemical basis of CI toxicity and their toxicodynamic interaction with mTOR
inhibitors is still poorly understood. Studies using a magnetic resonance
spectroscopy-based metabonomic approach indicate that CI toxicity is caused by
drug-induced mitochondrial dysfunction and that mTOR inhibitors enhance the
negative effects of CIs on cell energy metabolism. N. Ref:: 77
----------------------------------------------------
[64]
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.
----------------------------------------------------
[65]
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
----------------------------------------------------
[66]
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
----------------------------------------------------
[67]
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
----------------------------------------------------
[68]
TÍTULO / TITLE: - B19 virus infection in
renal transplant recipients.
REVISTA
/ JOURNAL: - J Clin Virol. Acceso gratuito al texto
completo.
●●
Enlace a la Editora de la Revista http://www.elsevier.com/gej-ng/29/46/32/show/Products/VIRUSINT/index.htt
●●
Cita: J Clinical Virology: <> 2003 Apr;26(3):361-8.
AUTORES
/ AUTHORS: - Cavallo R; Merlino C; Re D; Bollero C;
Bergallo M; Lembo D; Musso T; Leonardi G; Segoloni GP; Ponzi AN
INSTITUCIÓN
/ INSTITUTION: - Virology Unit, Department of Public Health
and Microbiology, University of Turin, Via Santena 9, 10126, Turin, Italy. rossana.cavallo@unito.it
RESUMEN
/ SUMMARY: - BACKGROUND: B19 virus infection with
persistent anaemia has been reported in organ transplant recipients. Detection
of B19 virus DNA in serum is the best direct marker of active infection.
OBJECTIVE: The present study evaluated the incidence and clinical role of
active B19 virus infection in renal transplant recipients presenting with
anaemia. STUDY DESIGN: Forty-eight such recipients were investigated by nested
PCR on serum samples. The controls were 21 recipients without anaemia. Active
HCMV infection was also investigated as a marker of high immunosuppression.
RESULTS AND CONCLUSIONS: In 11/48 (23%) patients B19 virus DNA was demonstrated
in serum versus only 1/21 (5%) of the controls. Ten of these 11 patients had
already been seropositive at transplantation and active infection occurred in
eight of them during the first 3 months after transplantation. The remaining
patient experienced a primary infection 9 months after transplantation. Eight
(73%) of these 11 patients displayed a concomitant HCMV infection and four
(36%) showed increasing serum creatinine levels but none developed
glomerulopathy; 3/11 (27%) recovered spontaneously from anaemia whereas 8/11
(73%) needed therapy. In conclusion, the relatively high occurrence (23%) of
B19 virus infection in patients presenting with anaemia, suggests that it
should be considered in the differential diagnosis of persistent anaemia in
renal transplant recipients. Presence of the viral DNA should be assessed early
from transplantation and the viral load should be monitored to follow
persistent infection and better understand the relation between active
infection and occurrence of anaemia, and to assess the efficacy of IVIG therapy
and/or immunosuppression reduction in clearing the virus. N. Ref:: 56
----------------------------------------------------
[69]
TÍTULO / TITLE: - A mitochondrial
perspective on cell death.
REVISTA
/ JOURNAL: - Trends Biochem Sci 2001 Feb;26(2):112-7.
AUTORES
/ AUTHORS: - Bernardi P; Petronilli V; Di Lisa F; Forte
M
INSTITUCIÓN
/ INSTITUTION: - Dept. of Biomedical Sciences, Viale
Giuseppe Colombo 3, I-35121, Padova, Italy. bernardi@civ.bio.unipd.it
RESUMEN
/ SUMMARY: - The role of mitochondria as crucial
participants in cell death programs is well established, yet the mechanisms
responsible for the release of mitochondrial activators and the role of BCL2
family proteins in this process remain controversial. Here, we point out the
limitations of current approaches used to monitor the physiological responses
of mitochondria during cell death, the implications arising from modern views
of mitochondrial structure, and briefly assess two proposed mechanisms for the
release of mitochondrial proteins during apoptosis. N. Ref:: 50
----------------------------------------------------
[70]
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
----------------------------------------------------
[71]
TÍTULO / TITLE: - Molecular diagnosis of
an Enterocytozoon bieneusi human genotype C infection in a moderately
immunosuppressed human immunodeficiency virus seronegative liver-transplant
recipient with severe chronic diarrhea.
REVISTA
/ JOURNAL: - J Clin Microbiol. Acceso gratuito al texto
completo a partir de los 6 meses de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://jcm.asm.org/
●●
Cita: J. Clinical Microbiology: <> 2001 Jun;39(6):2371-2.
AUTORES
/ AUTHORS: - Sing A; Tybus K; Heesemann J; Mathis
A N. Ref:: 5
----------------------------------------------------
[72]
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
----------------------------------------------------
[73]
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
----------------------------------------------------
[74]
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.
----------------------------------------------------
[75]
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
----------------------------------------------------
[76]
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
----------------------------------------------------
[77]
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
----------------------------------------------------
[78]
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.
----------------------------------------------------
[79]
TÍTULO / TITLE: - Vascular and cellular
mechanisms of chronic renal allograft dysfunction.
REVISTA
/ JOURNAL: - Transplantation 2001 Jun 15;71(11
Suppl):SS37-41.
AUTORES
/ AUTHORS: - Morris RE
INSTITUCIÓN
/ INSTITUTION: - Stanford University School of Medicine,
California, United States. N.
Ref:: 29
----------------------------------------------------
[80]
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
----------------------------------------------------
[81]
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
----------------------------------------------------
[82]
TÍTULO / TITLE: - Monitoring of cellular
resistance to cancer chemotherapy.
REVISTA
/ JOURNAL: - Hematol Oncol Clin North Am 2002
Apr;16(2):357-72, vi.
AUTORES
/ AUTHORS: - Krishan A; Arya P
INSTITUCIÓN
/ INSTITUTION: - Radiation Oncology Department, University
of Miami Medical School, Division of Experimental Therapeutics (R-71), P.O. Box
01690, Miami, FL 33101, USA. akrishan@med.miami.edu
RESUMEN
/ SUMMARY: - Cellular resistance to a broad spectrum of
natural products used as antitumor drugs is believed to be a major cause for
the failure of chemotherapy. Flow cytometry has been used for monitoring the
expression of drug resistance markers, determining accumulation of fluorescent
drugs, and for screening of drugs that enhance chemosensitivity by blocking
efflux and enhancing drug retention. This article reviews recent developments
in our understanding of the multiple drug resistance phenotype and the use of
flow cytometry for the study of drug efflux and its modulation in human tumor
cells. N. Ref:: 77
----------------------------------------------------
[83]
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
----------------------------------------------------
[84]
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
----------------------------------------------------
[85]
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
----------------------------------------------------
[86]
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
----------------------------------------------------
[87]
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
----------------------------------------------------
[88]
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
----------------------------------------------------
[89]
TÍTULO / TITLE: - Regulation of MAPK
signaling pathways through immunophilin-ligand complex.
REVISTA
/ JOURNAL: - Curr Top Med Chem 2003;3(12):1358-67.
AUTORES
/ AUTHORS: - Matsuda S; Koyasu S
INSTITUCIÓN
/ INSTITUTION: - Department of Microbiology and Immunology,
Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo
160-8582, Japan.
RESUMEN
/ SUMMARY: - It is well established that the
immunosuppressive effects of cyclosporin A (CsA) and FK506 (also known as
tacrolimus) are mediated through binding to their cognate cellular proteins
cyclophilin and FKBP (collectively termed immunophilins), respectively.
Biochemical analysis had revealed that cyclophilin-CsA and FKBP-FK506 complexes
bind to and inactivate Ca(2+)-dependent serine/threonine phosphatase
calcineurin. Since calcineurin regulates nuclear translocation and subsequent
activation of nuclear factor of activated T cells (NFAT) transcription factors
that is one of essential steps for cytokine gene expression in activated T
cells, it is believed that inhibition of calcineurin is a molecular basis of
the immunosuppressive properties of CsA and FK506. However, recent studies
indicate that both CsA and FK506 can block activation of JNK and p38 signaling
pathways during T cell activation. CsA and FK506, thus, have two distinct
mechanisms of action; one is the inhibition of the protein phosphatase activity
of calcineurin, leading to the blockade of the nuclear translocation of NFAT
transcription factors, and the other is the suppression of JNK and p38
activation pathways. It is likely that the presence of two distinct targets in
T cell activation makes CsA and FK506 highly potent immunosuppressive drugs.
Here we discuss the action of immunophilin-ligand complexes on JNK and p38
activation pathways. We also argue the possibility of immunotherapeutic
application targeting at JNK and p38 signaling pathways. N. Ref:: 121
----------------------------------------------------
[90]
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
----------------------------------------------------
[91]
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
----------------------------------------------------
[92]
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
----------------------------------------------------
[93]
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
----------------------------------------------------
[94]
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
----------------------------------------------------
[95]
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
----------------------------------------------------
[96]
TÍTULO / TITLE: - Mechanisms of action of
therapeutics in idiopathic thrombocytopenic purpura.
REVISTA
/ JOURNAL: - J Pediatr Hematol Oncol 2003 Dec;25 Suppl
1:S52-6.
AUTORES
/ AUTHORS: - Cines DB; McKenzie SE; Siegel DL
INSTITUCIÓN
/ INSTITUTION: - University of Pennsylvania School of
Medicine, Department of Pathology and Laboratory Medicine, 513A Stellar-Chance,
422 Curie Boulevard, Philadelphia, PA 19104, USA. dcines@mail.med.upenn.edu
RESUMEN
/ SUMMARY: - Idiopathic thrombocytopenic purpura (ITP)
is a common immune disorder caused by platelet-reactive autoantibodies.
Antibody-coated platelets are cleared more rapidly from the circulation, often
in the spleen, than they can be replaced by compensatory stimulation of
platelet production in the bone marrow. In some patients, platelet production
is depressed as well. ITP in adults does not generally remit spontaneously, and
most patients require treatment to prevent bleeding at one time or another.
Therapy with corticosteroids, danazol, intravenous immune globulin, anti-D
antibody, and several other agents inhibits clearance of the antibody-coated
platelets but is rarely curative. Most patients will sustain a hemostatic
response after splenectomy, although relapses may occur at any time. Patients may
be more responsive to these same modalities after splenectomy, but treatment
with an immunosuppressant that inhibits T- and B-cell function and cooperation,
including azathioprine, cyclophosphamide, cyclosporine, mycophenolate mofetil,
or anti-CD20, may be required. Antiviral therapy is useful in patients with HIV
or hepatitis C infection, but no consensus has been reached as to the efficacy
of antibiotics to eradicate Helicobacter pylori. Promising results have been
seen in several patients treated with a modified thrombopoietin. It may be
possible to design therapeutics that exploit the apparent restricted
immunoglobulin gene usage by antiplatelet antibodies, perhaps in the form of
engineered anti-idiotypic antibodies or other compounds that specifically
target autoantibody-producing B cells. Rationale therapy awaits a more thorough
understanding of autoantibody production.
N. Ref:: 46
----------------------------------------------------
[97]
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
----------------------------------------------------
[98]
TÍTULO / TITLE: - Molecular mechanisms of
renal allograft fibrosis.
REVISTA
/ JOURNAL: - Br J Surg 2001 Nov;88(11):1429-41.
●●
Enlace al texto completo (gratuito o de pago) 1046/j.0007-1323.2001.01867.x
AUTORES
/ AUTHORS: - Waller JR; Nicholson ML
INSTITUCIÓN
/ INSTITUTION: - Division of Transplant Surgery, University
of Leicester, Leicester, UK. julian@waller79.fsnet.co.uk
RESUMEN
/ SUMMARY: - BACKGROUND: Chronic graft nephropathy
(CGN) remains the leading cause of renal allograft loss after the first year
following transplantation. Histologically it is characterized by
glomerulosclerosis, intimal hyperplasia and interstitial fibrosis. The
pathogenesis is unclear, but is likely to involve both immunological and
non-immunological factors. Despite improvements in short-term graft survival
rates, new immunosuppressive regimens have made no impact on CGN. METHODS: A
review of the current literature on renal transplantation, novel
immunosuppression regimens and advances in the molecular pathogenesis of renal
allograft fibrosis was performed. RESULTS AND CONCLUSION: Recent advances in
understanding of the underlying molecular mechanisms involved suggest autocrine
secretion of cytokines and growth factors, especially transforming growth
factor beta, are associated with a change in fibroblast phenotype leading to
the deposition of extracellular matrix. Repeated insults trigger upregulation of
the tissue inhibitors of matrix metalloproteinases, favouring accumulation of
extracellular matrix. To date, no drug has proved effective in inhibiting or
reducing allograft fibrosis. The deleterious consequences of chronic
immunosuppression on the development of such fibrosis are now recognized; newer
immunosuppressive drugs, including rapamycin and mycophenolate mofetil, reduce
profibrotic gene expression in both experimental and clinical settings, and
offer potential strategies for prolonging allograft survival. N. Ref:: 155
----------------------------------------------------
[99]
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
----------------------------------------------------
[100]
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.
----------------------------------------------------
[101]
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
----------------------------------------------------
[102]
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
----------------------------------------------------
[103]
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
----------------------------------------------------
[104]
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
----------------------------------------------------
[105]
TÍTULO / TITLE: - Cyclophilin D as a drug
target.
REVISTA
/ JOURNAL: - Curr Med Chem 2003 Aug;10(16):1485-506.
AUTORES
/ AUTHORS: - Waldmeier PC; Zimmermann K; Qian T;
Tintelnot-Blomley M; Lemasters JJ
INSTITUCIÓN
/ INSTITUTION: - Nervous System Research, Novartis Pharma
Ltd., CH-4002 Basel, Switzerland. peter.waldmeier@pharma.novartis.com
RESUMEN
/ SUMMARY: - The mitochondrial permeability transition
(MPT) plays an important role in damage-induced cell death, and agents inhibiting
the MPT may have a therapeutic potential for treating human conditions such as
ischemia/reperfusion injury, trauma, and neurodegenerative diseases. The
mitochondrial matrix protein, cyclophilin D (CYP D), a member of a family of
highly homologous peptidylprolyl cis-trans isomerases (PPIases), plays a
decisive role in MPT, being an integral constituent of the MPT pore. Other
putative MPT pore proteins include the adenine nucleotide translocator (ANT)
and the voltage-dependent anion channel (VDAC). In an alternative model, the
MPT pore is formed by clusters of misfolded membrane proteins outlining aqueous
channels that are regulated by CYP D and other chaperone-like proteins. Like
cyclophilin A (CYP A) and other cyclophilin family members, CYP D is targeted
by the immunosuppressant cyclosporin A (CsA). CsA is cytoprotective in many
cellular and animal models, but protection may result from either inhibition of
the MPT through an interaction with CYP D or inhibition of calcineurin-mediated
dephosphorylation of BAD through an interaction with CYP A. The relevance of
MPT inhibition by CsA for its cytoprotective effects is well documented in many
cellular models. Mechanisms of action in vivo are more difficult to define, and
accordingly the evidence is as yet less compelling in in vivo animal models of
ischemia/reperfusion injury, trauma and neurodegenerative diseases.
Notwithstanding, CYP D is a drug target of high interest. Structural
considerations suggest feasibility of designing CYP D ligands without immunosuppressant
properties. This is highly desirable, since they have the potential of being
useful therapeutic agents in a variety of disease states. It might be a tougher
challenge to obtain compounds specific for CYP D vs. other cyclophilins, and/or
of small molecular weight, allowing brain penetration to make them suitable for
treating neurodegenerative diseases. N.
Ref:: 204
----------------------------------------------------
[106]
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
----------------------------------------------------
[107]
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
----------------------------------------------------
[108]
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
----------------------------------------------------
[109]
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
----------------------------------------------------
[110]
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.
----------------------------------------------------
[111]
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.
----------------------------------------------------
[112]
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
----------------------------------------------------
[113]
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
----------------------------------------------------
[114]
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
----------------------------------------------------
[115]
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
----------------------------------------------------
[116]
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
----------------------------------------------------
[117]
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
----------------------------------------------------
[118]
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
----------------------------------------------------
[119]
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
----------------------------------------------------
[120]
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
----------------------------------------------------
[121]
TÍTULO / TITLE: - An alternative
mechanism for the immunosuppressive effect of transfusion.
REVISTA
/ JOURNAL: - Vox Sang 2002 Aug;83 Suppl 1:417-9.
AUTORES
/ AUTHORS: - Dzik WH; Mincheff M; Puppo F
INSTITUCIÓN
/ INSTITUTION: - Blood Transfusion Service, J-224,
Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. sdzik@partners.org N. Ref:: 15
----------------------------------------------------
[122]
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
----------------------------------------------------
[123]
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
----------------------------------------------------
[124]
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
----------------------------------------------------
[125]
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
----------------------------------------------------
[126]
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
----------------------------------------------------
[127]
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
----------------------------------------------------
[128]
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
----------------------------------------------------
[129]
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.
----------------------------------------------------
[130]
TÍTULO / TITLE: - Polyomavirus BK
nephropathy: a (re-)emerging complication in renal transplantation.
REVISTA
/ JOURNAL: - Am J Transplant 2002 Jan;2(1):25-30.
AUTORES
/ AUTHORS: - Hirsch HH
INSTITUCIÓN
/ INSTITUTION: - Department of Internal Medicine,
University of Basel, Switzerland. hans.hirsch@unibas.ch
RESUMEN
/ SUMMARY: - Persisting polyomavirus replication is now
widely recognized as a (re-)emerging cause of renal allograft dysfunction. Up
to 5% of renal allograft recipients can be affected about 40weeks (range 6-150)
post-transplantation. Progression to irreversible failure of the allograft has
been observed in up to 45% of all cases. The BK virus strain is involved in the
majority of the cases. Risk factors may include treatment of rejection episodes
and increasing viral replication under potent immunosuppressive drugs such as
tacrolimus, sirolimus or mycophenolate. The diagnosis requires the histological
demonstration of nuclear polyomavirus inclusions in affected tubular epithelial
cells. Interstitial inflammatory infiltrates and fibrosis become more prominent
in the persisting disease and may be difficult to distinguish from (coexisting)
rejection. Detection of polyomavirus-inclusion bearing cells (‘decoy cells’) in
the urine and quantification of BK virus DNA in the plasma have been proposed
as surrogate markers for polyomavirus replication and allograft disease,
respectively. Antiviral treatment is not yet established; however, reports of
treatment with cidofovir are encouraging. Current management aims at the judicious
modification and/or reduction of immunosuppression which, in view of preceding
or concurrent rejection, is not without risk.
N. Ref:: 51
----------------------------------------------------
[131]
TÍTULO / TITLE: - Methods and assays to
investigate nuclear export.
REVISTA
/ JOURNAL: - Curr Top Microbiol Immunol
2001;259:119-28.
AUTORES
/ AUTHORS: - Stauber RH
INSTITUCIÓN
/ INSTITUTION: - Institute for Clinical and Molecular
Virology, University of Erlangen-Nurnberg, Schlossgarten 4, 91054 Erlangen,
Germany. N. Ref:: 34
----------------------------------------------------
[132]
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.
----------------------------------------------------
[133]
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
----------------------------------------------------
[134]
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
----------------------------------------------------
[135]
TÍTULO / TITLE: - Mechanisms of
resistance to rapamycins.
REVISTA
/ JOURNAL: - Drug Resist Updat 2001 Dec;4(6):378-91.
●●
Enlace al texto completo (gratuito o de pago) 1054/drup.2002.0227
AUTORES
/ AUTHORS: - Huang S; Houghton PJ
INSTITUCIÓN
/ INSTITUTION: - Department of Molecular Pharmacology, St.
Jude Children’s Research Hospital, Memphis, TN 38105-2794, USA.
RESUMEN
/ SUMMARY: - Rapamycins represent a novel family of
anticancer agents, currently including rapamycin and its derivatives, CCI-779
and RAD001. Rapamycins inhibit the function of the mammalian target of
rapamycin (mTOR), and potently suppress tumor cell growth by arresting cells in
G1 phase or potentially inducing apoptosis of cells, in culture or in xenograft
tumor models. However, recent data indicate that genetic mutations or
compensatory changes in tumor cells influence the sensitivity of rapamycins.
First, mutations of mTOR or FKBP12 prevent rapamycin from binding to mTOR,
conferring rapamycin resistance. Second, mutations or defects of mTOR-regulated
proteins, including S6K1, 4E-BP1, PP2A-related phosphatases, and p27(Kip1) also
render rapamycin insensitivity. In addition, the status of ATM, p53, PTEN/Akt
and 14-3-3 are also associated with rapamycin sensitivity. To better explore
the role of rapamycins against tumors, this review will summarize the current
knowledge of the mechanism of action of rapamycins, and progress in
understanding mechanisms of acquired or intrinsic resistance. N. Ref:: 126
----------------------------------------------------
[136]
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.
----------------------------------------------------
[137]
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
----------------------------------------------------
[138]
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
----------------------------------------------------
[139]
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
----------------------------------------------------
[140]
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
----------------------------------------------------
[141]
- 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
----------------------------------------------------
[142]
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.
----------------------------------------------------
[143]
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
----------------------------------------------------
[144]
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
----------------------------------------------------
[145]
TÍTULO / TITLE: - Sirolimus: its
discovery, biological properties, and mechanism of action.
REVISTA
/ JOURNAL: - Transplant Proc 2003 May;35(3
Suppl):7S-14S.
AUTORES
/ AUTHORS: - Sehgal SN
INSTITUCIÓN
/ INSTITUTION: - Wyeth-Ayerst Research, Collegeville,
Pennsylvania, USA.
RESUMEN
/ SUMMARY: - Sirolimus is the USAN-assigned generic
name for the natural product rapamycin. Sirolimus is produced by a strain of
Streptomyces hygroscopicus, isolated from a soil sample collected from Rapa Nui
commonly known as Easter Island. Although sirolimus was isolated as an
antifungal agent with potent anticandida activity, subsequent studies revealed
impressive antitumor and immunosuppressive activities. Sirolimus demonstrates
activity against several murine tumors, such as B16 43 melanocarcinoma, Colon
26 tumor, EM ependymoblastoma, and mammary and colon 38 solid tumors. Sirolimus
is a potent inhibitor of antigen-induced proliferation of T cells, B cells, and
antibody production. Demonstration of the potent immunosuppressive activity of
sirolimus in animal models of organ transplantation led to clinical trials and
subsequent approval by regulatory authorities for prophylaxis of renal graft
rejection. Interest in sirolimus as an immunosuppressive therapy in organ
transplantation derives from its unique mechanism of action, its unique
side-effect profile, and its ability to synergize with other immunosuppressive
agents. The molecular mechanism underlying the antifungal, antiproliferative,
and immunosuppressive activities of sirolimus is the same. Sirolimus forms an
immunosuppressive complex with intracellular protein, FKBP12. This complex
blocks the activation of the cell-cycle-specific kinase, TOR. The downstream
events that follow the inactivation of TOR result in the blockage of cell-cycle
progression at the juncture of G1 and S phase.
N. Ref:: 78
----------------------------------------------------
[146]
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
----------------------------------------------------
[147]
TÍTULO / TITLE: - Cyclosporine lymphocyte
level and lymphocyte count: new guidelines for tailoring immunosuppressive
therapy.
REVISTA
/ JOURNAL: - Transplant Proc 2003 Nov;35(7):2742-4.
AUTORES
/ AUTHORS: - Barbari A; Stephan A; Masri M; Mourad N;
Kamel G; Kilani H; Karam A; Daya IA
INSTITUCIÓN
/ INSTITUTION: - Nephrology and Transplantation Unit, Rizk
Hospital, Beirut, Lebanon. lird@cyberia.net.lb
----------------------------------------------------
[148]
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
----------------------------------------------------
[149]
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
----------------------------------------------------
[150]
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
----------------------------------------------------
[151]
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
----------------------------------------------------
[152]
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
----------------------------------------------------
[153]
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
----------------------------------------------------
[154]
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
----------------------------------------------------
[155]
TÍTULO / TITLE: - Bone marrow aplasia
after pipobroman: an immune-mediated mechanism?
REVISTA
/ JOURNAL: - Br J Haematol 2001 Dec;115(3):713-4.
AUTORES
/ AUTHORS: - Triffet A; Straetmans N; Ferrant A N. Ref:: 7
----------------------------------------------------
[156]
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
----------------------------------------------------
[157]
TÍTULO / TITLE: - Mechanisms of
clinically relevant drug interactions associated with tacrolimus.
REVISTA
/ JOURNAL: - Clin Pharmacokinet 2002;41(11):813-51.
AUTORES
/ AUTHORS: - Christians U; Jacobsen W; Benet LZ; Lampen
A
INSTITUCIÓN
/ INSTITUTION: - Department of Anesthesiology, University
of Colorado Health Sciences Center, Denver, Colorado, USA. uwe.christians@uchsc.edu
RESUMEN
/ SUMMARY: - The clinical management of tacrolimus, a
macrolide used as immunosuppressant after transplantation, is complicated by
its narrow therapeutic index in combination with inter- and intraindividually
variable pharmacokinetics. As a substrate of cytochrome P450 (CYP) 3A enzymes
and P-glycoprotein, tacrolimus interacts with several other drugs used in
transplantation medicine, which also are known CYP3A and/or P-glycoprotein
inhibitors and/or inducers. In clinical studies, CYP3A/P-glycoprotein
inhibitors and inducers primarily affect oral bioavailability of tacrolimus
rather than its clearance, indicating a key role of intestinal P-glycoprotein
and CYP3A. There is an almost complete overlap between the reported clinical
drug interactions of tacrolimus and those of cyclosporin. However, in
comparison with cyclosporin, only few controlled drug interaction studies have
been carried out, but tacrolimus drug interactions have been extensively
studied in vitro. These results are inconsistent and are of poor predictive
value for clinical drug interactions because of false negative results.
P-glycoprotein regulates distribution of tacrolimus through the blood-brain
barrier into the brain as well as distribution into lymphocytes. Interaction of
other drugs with P-glycoprotein may change tacrolimus tissue distribution and
modify its toxicity and immunosuppressive activity. There is evidence that
ethnic and gender differences exist for tacrolimus drug interactions.
Therapeutic drug monitoring to guide dosage adjustments of tacrolimus is an
efficient tool to manage drug interactions. In the near future, progress can be
expected from studies evaluating potential pharmacokinetic interactions caused
by herbal preparations and food components, the exact biochemical mechanism
underlying tacrolimus toxicity, and the potential of inhibition of CYP3A and
P-glycoprotein to improve oral bioavailability and to decrease intraindividual
variability of tacrolimus pharmacokinetics.
N. Ref:: 385
----------------------------------------------------
[158]
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
----------------------------------------------------
[159]
TÍTULO / TITLE: - Role of apoptosis in
the pathogenesis of acute renal failure.
REVISTA
/ JOURNAL: - Curr Opin Nephrol Hypertens 2002
May;11(3):301-8.
AUTORES
/ AUTHORS: - Bonegio R; Lieberthal W
INSTITUCIÓN
/ INSTITUTION: - Renal Section, Department of Medicine,
Boston Medical Center, Boston University School of Medicine, Boston,
Massachusetts 02118, USA.
RESUMEN
/ SUMMARY: - Renal tubular cells die by apoptosis as
well as necrosis in experimental models of ischemic and toxic acute renal
failure as well as in humans with acute tubular necrosis. It is not yet
possible, however, to determine the relative contribution of these two forms of
cell death to loss of renal tubular cells in acute tubular necrosis. The
beneficial effect of administering growth factors to animals with acute tubular
necrosis is probably related to the potent antiapoptotic (survival) effects of
growth factors as well as to their proliferative effects. Rapamycin inhibits
both of these effects of growth factors and delays the recovery of renal
function after acute tubular necrosis by inhibiting renal tubular cell
regeneration and by increasing renal tubular cell loss by apoptosis. The
administration of caspase inhibitors ameliorates ischemia-reperfusion injury in
multiple organs including the kidney. However, the extent to which this
protective effect of caspase inhibition is caused by reduced intrarenal
inflammation, or by amelioration of renal tubular cell loss due to apoptosis,
remains uncertain. In addition to caspase inhibition, the apoptotic pathway
offers many potential targets for therapeutic interventions to prevent renal
tubular cell apoptosis. N.
Ref:: 82
----------------------------------------------------
[160]
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
----------------------------------------------------
[161]
TÍTULO / TITLE: - Calcineurin inhibitors
and sirolimus: mechanisms of action and applications in dermatology.
REVISTA
/ JOURNAL: - Clin Exp Dermatol 2002 Oct;27(7):555-61.
AUTORES
/ AUTHORS: - Reynolds NJ; Al-Daraji WI
INSTITUCIÓN
/ INSTITUTION: - Department of Dermatology, Medical School,
University of Newcastle upon Tyne, UK. N.J.Reynolds@ncl.ac.uk
RESUMEN
/ SUMMARY: - Controlled trials and clinical experience
indicate that systemic cyclosporin A and tacrolimus are effective treatments
for psoriasis, and that cyclosporin A also improves atopic eczema. A variety of
other inflammatory and non-inflammatory skin diseases are probably also
responsive to these drugs. However, the widespread and longer-term use of
cyclosporin A and tacrolimus are limited by side effects. The molecular
mechanisms of action of cyclosporin A, tacrolimus and a related drug,
sirolimus, have been well defined in T cells and involve inhibition of critical
signalling pathways that regulate T cell activation. For example cyclosporin
and tacrolimus inhibit calcineurin phosphatase activity and thereby inhibit
activation of the transcription factor NFAT. The therapeutic efficacy of
topical calcineurin inhibitors in atopic eczema have restimulated interest in
the mechanism of action of these drugs in skin disease. Recently the expression
pattern of calcineurin and NFAT has been defined in non-immune tissues
including the akin. The relevance of this to the mechanism of action of
systemic and topical calcineurin inhibitors and sirolimus in skin disorders is
discussed. N. Ref:: 54
----------------------------------------------------
[162]
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
----------------------------------------------------
[163]
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
----------------------------------------------------
[164]
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.
----------------------------------------------------
[165]
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
----------------------------------------------------
[166]
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
----------------------------------------------------
[167]
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
----------------------------------------------------
[168]
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
----------------------------------------------------
[169]
TÍTULO / TITLE: - Cap-dependent
translation and control of the cell cycle.
REVISTA
/ JOURNAL: - Prog Cell Cycle Res 2003;5:469-75.
AUTORES
/ AUTHORS: - Cormier P; Pyronnet S; Salaun P;
Mulner-Lorillon O; Sonenberg N
INSTITUCIÓN
/ INSTITUTION: - Station Biologique de Roscoff, Universite
Pierre et Marie Curie (EI 37), CNRS-UMR 7127, (INSU), BP 74, 29682 Roscoff,
France.
RESUMEN
/ SUMMARY: - The control of gene expression at the
translational level has emerged in the past decade as an important aspect of
cell growth, proliferation and malignant transformation. Translation is
primarily regulated at the initiation step, and mitogen-dependent signaling
pathways converge to modulate the activity of translation initiation factors.
In most tumors tested, at least one translation initiation factor is
overexpressed and overexpression of translation initiation factors often
provokes transformation. Malignant transformation could be caused by the
increased translation of a subset of mRNAs encoding important proteins which
are required for cell growth and proliferation. These mRNAs usually possess
regulatory sequences that render their translation more sensitive to changes in
the activity of translation initiation factors. In this chapter, we describe
recent advances illustrating the importance of translation in cell cycle
progression and cell transformation. Control of translation initiation may
represent an excellent target for antitumor drugs. N. Ref:: 96
----------------------------------------------------
[170]
TÍTULO / TITLE: - Rapamycins: mechanism
of action and cellular resistance.
REVISTA
/ JOURNAL: - Cancer Biol Ther 2003 May-Jun;2(3):222-32.
AUTORES
/ AUTHORS: - Huang S; Bjornsti MA; Houghton PJ
INSTITUCIÓN
/ INSTITUTION: - Department of Molecular Pharmacology, St.
Jude Children’s Research Hospital, 332 N. Lauderdale, Memphis, Tennessee 38105,
USA.
RESUMEN
/ SUMMARY: - Rapamycins are macrocyclic lactones that
possess immunosuppressive, antifungal and antitumor properties. The parent
compound, rapamycin, is approved as an immunosup-pressive agent for preventing
rejection in patients receiving organ transplantation. Two analogues, CCI-779
and RAD001 are currently being investigated as anticancer agents. Rapamycins
first bind a cyclophilin FKBP12, and this complex binds and inhibits the
function of mTOR (mammalian target of rapamycin) a serine/threonine (Ser/Thr)
kinase with homology to phosphatidylinositol 3’ kinase. Currently, as mTOR is
the only identified target, this places rapamycins in a unique position of
being the most selective kinase inhibitor known. Consequently these agents have
been powerful tools in elucidating the role of mTOR in cellular growth,
proliferation, survival and tumorigenesis. Increasing evidence suggests that
mTOR acts as a central controller sensing cellular environment (nutritional status
or mitogenic stimulation) and regulating translation initiation through the
eukaryotic initiation factor 4E, and ribosomal p70 S6 kinase pathways. Here we
review the conserved TOR signaling pathways, conceptual basis for tumor
selectivity, and the mechanisms of resistance to this class of antitumor
agent. N. Ref:: 137
----------------------------------------------------
[171]
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
----------------------------------------------------
[172]
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
----------------------------------------------------
[173]
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
----------------------------------------------------
[174]
TÍTULO / TITLE: - Atopic dermatitis:
review of immunopathogenesis and advances in immunosuppressive therapy.
REVISTA
/ JOURNAL: - Australas J Dermatol 2002
Nov;43(4):247-54.
AUTORES
/ AUTHORS: - Meagher LJ; Wines NY; Cooper AJ
INSTITUCIÓN
/ INSTITUTION: - Department of Dermatology, Royal North
Shore Hospital, Sydney, New South Wales, Australia.
RESUMEN
/ SUMMARY: - This paper reviews the theories of the
pathogenesis of atopic dermatitis (AD), with a particular emphasis on its
immunopathogenesis. The contribution of predisposing factors, immunopathogenic
factors and provoking factors in the pathogenesis of AD are considered.
Predisposing factors explored in this article include genetics and the
disturbance of skin function. Immunopathogenic factors reviewed include T cell
dysfunction, biphasic cytokine expression and the role of immunoglobulin E.
Provoking factors considered include microbial factors, psychosomatic
interactions, contact allergens and irritants, inhalant allergens, food and
climate. Immunosuppressive treatments reviewed include cyclosporin,
azathioprine, methotrexate, tacrolimus, interferon-gamma, phosphodiesterase
inhibitors and pimecrolimus (SDZ ASM 981).
N. Ref:: 80
----------------------------------------------------
[175]
TÍTULO / TITLE: - Novel immunosuppressive
agents in tolerance induction.
REVISTA
/ JOURNAL: - Curr Drug Targets Cardiovasc Haematol
Disord 2002 Dec;2(2):97-103.
AUTORES
/ AUTHORS: - Krieger NR; Knechtle SJ
INSTITUCIÓN
/ INSTITUTION: - Division of Organ Transplantation,
Department of Surgery, University of Wisconsin Medical School, 600 Highland
Avenue, Madison, WI 53792, USA.
RESUMEN
/ SUMMARY: - Induction of transplantation tolerance
remains a much sought-after but elusive goal with a potential promise of
rendering patients free of long-term immunosuppressive drugs while maintaining
good organ transplant function indefinitely. All currently studied strategies
toward transplantation tolerance include using immunosuppressive agents for a
limited time period to achieve tolerance. There are a growing number of agents
that lend themselves to tolerance induction and these agents are considered
herein. Such agents generally fall into the categories of lymphocyte depletion,
costimulation blockade, and adjunctive agents such as rapamycin. Preliminary
data using donor stem cells suggests that embryonic stem cells may have
substantial advantages over conventional donor bone marrow for tolerance
induction. These preliminary results are briefly reviewed as well. Tolerance
has been achieved in a small number of organ transplant patients and such
successes suggest that progress in the clinical arena is happening and is an
obtainable result. N.
Ref:: 52
----------------------------------------------------
[176]
TÍTULO / TITLE: - Pregnancy in renal
transplant recipients.
REVISTA
/ JOURNAL: - Adv Ren Replace Ther 2003 Jan;10(1):40-7.
●●
Enlace al texto completo (gratuito o de pago) 1053/jarr.2003.50002
AUTORES
/ AUTHORS: - Hou S
INSTITUCIÓN
/ INSTITUTION: - Section of Nephrology, Department of
Medicine, Loyola University Medical Center, Chicago, IL, USA. shou@lumc.edu
RESUMEN
/ SUMMARY: - Most women of childbearing age who receive
a renal transplant have a return of normal menses and have the ability to
become pregnant. Most studies indicate that pregnancy does not adversely affect
the transplant kidney’s survival as long as renal function is good and serum
creatinine is stable before pregnancy. The experience with immunosuppressive
drugs has been surprisingly reassuring with no increase in congenital anomalies
with cyclosporine, prednisone, and azathioprine. There is little experience
with newer drugs. Pregnant transplant recipients need to be monitored for
opportunistic infections, which may adversely affect the fetus, including
herpes, toxoplasmosis, and CMV. Hypertension, urinary tract infections, and
anemia are other common problems in pregnant transplant recipients. Despite a
high frequency of premature births, over 80% of pregnancies result in surviving
infants. N. Ref:: 38
----------------------------------------------------
[177]
TÍTULO / TITLE: - Sirolimus: a
comprehensive review.
REVISTA
/ JOURNAL: - Expert Opin Pharmacother 2001
Nov;2(11):1903-17.
AUTORES
/ AUTHORS: - Kahan BD
INSTITUCIÓN
/ INSTITUTION: - Division of Immunology and Organ
Transplantation, University of Texas-Houston, 6431 Fannin, Suite 6.240,
Houston, TX 77030, USA. barry.d.kahan@uth.tmc.edu
RESUMEN
/ SUMMARY: - Sirolimus (Rapamune), Wyeth-Ayerst,
Madison, NJ) is a new, potent, immunosuppressant that is emerging as a
foundation for long-term immunosuppressive therapy in renal transplantation.
The drug acts during both co-stimulatory activation and cytokine-driven
pathways via a unique mechanism: inhibition of a multifunctional
serine-threonine kinase, mammalian target of rapamycin (mTOR). Although there
is no a priori reason to assume it, sirolimus displays a synergistic
interaction to enhance the efficacy of cyclosporin A (CsA). In trials wherein
the concentrations of CsA and sirolimus were tightly controlled, rates of acute
rejection episodes were < 10%, despite markedly reduced exposures to each
agent. In pivotal multi-centre blinded dose-controlled trials, the rates of
acute rejection episodes within 12 months following administration of 2 or 5
mg/day sirolimus in combination with CsA and steroids were reduced to 19 and
14%, respectively. Since the inhibitory effect of sirolimus disables virtually
all responses to cytokine mediators due to the widespread involvement of mTOR
in multiple signalling pathways, the agent is likely also to retard
proliferation of endothelial and vascular smooth muscle cells, an important
component of the immuno-obliterative processes associated with chronic
rejection. The advantages of this unique therapeutic action combined with an
intrinsic lack of nephrotoxicity are counterbalanced by myelosuppressive and
hyperlipidaemic side effects. Ongoing studies are assessing whether the
long-term benefits of sirolimus to permit reduction in exposure to or
elimination of calcineurin inhibitors ameliorate the progression of chronic
nephropathy, the condition that erodes long-term renal transplant
survival. N. Ref:: 108
----------------------------------------------------
[178]
TÍTULO / TITLE: - Mechanisms and
management of gingival overgrowth in paediatric transplant recipients: a
review.
REVISTA
/ JOURNAL: - Int J Paediatr Dent 2003 Jul;13(4):220-9.
AUTORES
/ AUTHORS: - Chabria D; Weintraub RG; Kilpatrick NM
INSTITUCIÓN
/ INSTITUTION: - Department of Dentistry, Royal Children’s
Hospital, Melbourne, Australia.
RESUMEN
/ SUMMARY: - Increasing numbers of children are
receiving solid organ transplants namely kidney, liver, heart and lung. Patient
survival rates following such transplants are essentially good with much of the
success attributable to the development of Cyclosporine A (CyA), an
immunosuppressive drug, that minimizes organ rejection. However the gingival
overgrowth (GO) associated with the use of CyA is not only disfiguring but in
paediatric recipients, may interfere with normal oral development and function.
OBJECTIVE: The aim of this review is to summarize current knowledge concerning
the aetiology, pathogenesis and management of gingival overgrowth. METHODS:
Literature pertaining to gingival overgrowth is reviewed with particular
reference to the paediatric population. Emphasis is placed on summarizing the
evidence pertaining to the effectiveness of intervention. CONCLUSION: CyA
undoubtedly causes gingival overgrowth, the effects and levels of which appears
to be more severe in younger patients. There is conflicting evidence as to the
effectiveness of oral hygiene regimes, antibiotics and surgery in reducing
overgrowth. The introduction of an alternative immunosuppressive agent (Tacrolimus)
offers potential as it does not appear to cause overgrowth, although research
to date is limited by the small sample size of many of the studies. This is an
area in which multicentre studies would be of great value. N. Ref:: 70
----------------------------------------------------
[179]
TÍTULO / TITLE: - New developments in
immunosuppressive therapy in renal transplantation.
REVISTA
/ JOURNAL: - Expert Opin Biol Ther 2002
Jun;2(5):483-501.
AUTORES
/ AUTHORS: - Gourishankar S; Turner P; Halloran P
INSTITUCIÓN
/ INSTITUTION: - Division of Nephrology and Immunology,
University of Alberta, Edmonton, Canada. gsita@hotmail.com
RESUMEN
/ SUMMARY: - The introduction of new immunosuppressive
agents and protocols has improved outcomes for renal transplant recipients by
decreasing the risk of rejection and by increasing the function and lifespan of
the allograft. This article reviews the major changes in the combinations of
therapies used: calcineurin inhibitors, target of rapamycin inhibitors,
mycophenolate mofetil, non-depleting monoclonal versus depleting monoclonal and
polyclonal antibodies for induction and increasing emphasis on protocols for
reduction or avoidance of steroids and calcineurin inhibitors. The new agents
with novel immunological targets such as anti-CD40 ligand, LEA29Y, FTY720,
anti-CD20 (rituximab, Rituxan, Mabthera) and anti-CH52 (alemtuzumab, Campath),
which are under development but have yet to survive the rigors of clinical
trials are also discussed. In the presence of low early rejection rates,
immunosuppressive therapy is setting new goals such as better graft function
(glomerular filtration rates), reduction in adverse effects such as
hypertension, hyperlipidaemia and drug toxicity and, above all, the prevention
of late graft deterioration. N.
Ref:: 156
----------------------------------------------------
[180]
TÍTULO / TITLE: - NF-kappaB in
transplantation: friend or foe?
REVISTA
/ JOURNAL: - Transpl Infect Dis 2001 Dec;3(4):212-9.
AUTORES
/ AUTHORS: - Tsoulfas G; Geller DA
INSTITUCIÓN
/ INSTITUTION: - Department of Surgery, University of
Pittsburgh, Starzl Transplant Institute, Pittsburgh, Pennsylvania 15213, USA.
RESUMEN
/ SUMMARY: - NF-kappaB is an inducible nuclear
transcription factor regulating the expression of many genes. NF-kappaB
activation may function as a master switch in a variety of immune and
inflammatory processes, including sepsis and transplant tolerance. In this
review, we summarize features of NF-kappaB regulation, as well as describe its
role in intracellular signal transduction pathways. Subsequently, we
concentrate on the role of NF-kappaB in the field of organ transplantation and
the role of NF-kappaB in organ ischemia/reperfusion injury and graft rejection.
Finally, potential therapeutic strategies are discussed to modify NF-kappaB
activity with certain immunosuppression medications, including cyclosporine,
tacrolimus, and glucocorticoids. N.
Ref:: 54
----------------------------------------------------
[181]
TÍTULO / TITLE: - Use of sirolimus in
kidney transplantation.
REVISTA
/ JOURNAL: - Prog Transplant 2001 Mar;11(1):29-32.
AUTORES
/ AUTHORS: - Podbielski J; Schoenberg L
INSTITUCIÓN
/ INSTITUTION: - University of Texas Medical School at
Houston, Houston, Tex., USA.
RESUMEN
/ SUMMARY: - Sirolimus, which has a distinctive
mechanism of action that inhibits cytokine-driven cell proliferation and
maturation, provides an exciting addition to the immunosuppressive regimen for
organ transplantation. A significant decrease in the number and severity of
rejection episodes has been noted when sirolimus is used; it also offers the
potential for patients to be withdrawn from steroids, making kidney
transplantation an option for many more potential recipients. Toxic conditions
such as hyperlipidemia, thrombocytopenia, and leukopenia become transient and
manageable with reduction of the sirolimus dose and/or countermeasure
therapy. N. Ref:: 9
----------------------------------------------------
[182]
TÍTULO / TITLE: - To transplant or not to
transplant recurrent hepatitis C and liver failure.
REVISTA
/ JOURNAL: - Clin Liver Dis 2003 Aug;7(3):615-29.
AUTORES
/ AUTHORS: - Forman LM
INSTITUCIÓN
/ INSTITUTION: - Division of Gastroenterology, and
Hepatology, University of Colorado Health Sciences Center, 4200 East Ninth
Avenue B-154, Denver, Colorado, CO 80262, USA. lisa.forman@UCHSC.edu
RESUMEN
/ SUMMARY: - In summary, re-OLT accounts for 10% of all
OLTs performed and is associated with significantly increased resource use, and
decreased survival compared with primary OLT. After transplantation into an
HCV-infected recipient, infection of the allograft by HCV is invariable. As
patients survive longer after liver transplantation, it is likely that
allograft failure related to HCV recurrence will occur. Results of re-OLT for
HCV are inferior to those of primary grafting, paralleling the results for
retransplantation for other indications. Many studies have demonstrated that
HCV infection significantly impairs patient and allograft survival after liver
retransplantation, regardless of etiology of allograft failure. Patient
survival rates with HCV infection are 57% to 65% at 1 year, as compared with
65% to 82% among patients without HCV infection. Experience with
retransplantation is limited, however, and studies are difficult to interpret
because of small sample sizes and lack of uniform definitions of survival, HCV
recurrence, and allograft failure. Similar to outcomes after retransplantation
for non-HCV related indications, the most common causes of death are sepsis and
multi-organ failure. The high mortality associated with retransplantation has
not universally been caused by recurrent disease, however recent studies have demonstrated
that re-recurrent HCV occurs and the natural history is similar, if not more
accelerated, after the second transplant. HCV infection may, in fact, increase
mortality in a group of patients already predisposed to an inferior outcome.
Preoperative serum creatinine and bilirubin have been consistently associated
with survival after retransplantation and favorable results are attainable with
strict selection criteria. The increasing use of expanded donor criteria, in
particular, LRLT, raises important practical and ethical issues with regards to
the HCV-positive transplant recipient and will become a challenge to the
transplant community as a whole. With the donor morbidity and mortality
associated with LRLT currently estimated at 32% and 0.3%, respectively, one
must determine how much risk is acceptable to the donor in relation to the
outcome in the recipient. This is especially true in HCV-infected recipients,
in whom HCV re-recurrence may occur in the second allograft and lead to
accelerated failure. LRLT, however, would not deplete the organ pool and would
lead to the use of scarce cadaveric organs to patients who are awaiting primary
liver transplantation. Despite inferior outcomes, a better tactic may be to
consider retransplantation for recurrent HCV in those whose primary transplant
was a LDLT, as the initial allograft did not deplete the donor pool. Given the
shortage of donor organs and the increasing number of patients with HCV-induced
allograft cirrhosis, identifying ways to improve allograft survival in
HCV-infected patients represents an important focus for further research.
Additional studies are needed to further explore the mechanisms underlying the
reduction in survival and to identify which HCV-positive individuals are at
greatest risk for poor survival. Studies are beginning to emerge that
demonstrate that HCV recurrence can be modified with combination antiviral
therapy and that the HCV virus can be eliminated. Additional longitudinal
prospective studies are needed to assess the exact impact of HCV on survival
after retransplantation, the effects of the newer immunosuppressive agents such
as sirolimus and mycophenolate mofetil on HCV, the use of preemptive antiviral
therapy on HCV eradication and fibrosis modification, and the appropriateness
of expanded donor criteria. Until we have longer follow-up and greater
experience with the HCV-positive recipient with allograft failure,
retransplantation should be considered a viable option for highly selected
patients, particularly in patients in whom renal failure and severe
hyperbilirubinemia have not occurred. N.
Ref:: 56
----------------------------------------------------
[183]
TÍTULO / TITLE: - Conversion from
cyclosporin to tacrolimus in paediatric liver transplant recipients.
REVISTA
/ JOURNAL: - Paediatr Drugs 2001;3(9):661-72.
AUTORES
/ AUTHORS: - Mazariegos GV; Salzedas AA; Jain A; Reyes
J
INSTITUCIÓN
/ INSTITUTION: - Thomas E. Starzl Transplantation
Institute, Children’s Hospital of Pittsburgh, University of Pittsburgh Medical
Center, PA 15213, USA. mazarieg@pitt.edu
RESUMEN
/ SUMMARY: - Substitution of cyclosporin with
tacrolimus should be considered for paediatric liver transplant recipients with
cyclosporin-associated complications such as hypertension, gum hyperplasia,
hirsutism, gynaecomastia and growth retardation, as well as recurrent or
refractory acute rejection, chronic duct injury or chronic rejection. Continued
experience with well tolerated drug administration and careful monitoring
during drug substitution has limited drug toxicity associated with tacrolimus
to a level comparable to or less than that associated with cyclosporin.
Successful outcome with long term graft salvage has been reported in up to 80%
of patients converted to tacrolimus because of acute rejection and 50% of
patients converted because of chronic rejection. Nearly all children converted
because of cyclosporin-related complications have a successful outcome.
Additional benefits of conversion to tacrolimus include improvement in growth
and resolution of hypertension, hirsutism and cushingoid facies. Complete
corticosteroid withdrawal is possible in up to 78% of children post-conversion.
Long term outcome in these patients may be optimised by conversion to tacrolimus
at an early stage of acute or chronic transplant rejection in order to minimise
the cumulative amount of immunosuppression. Avoidance of cyclosporin-related
toxicity and minimisation of corticosteroid therapy may further improve patient
compliance to drug therapy. N.
Ref:: 48
----------------------------------------------------
[184]
TÍTULO / TITLE: - Alternatives to
immunosuppressive drugs in human islet transplantation.
REVISTA
/ JOURNAL: - Curr Diab Rep 2002 Aug;2(4):377-82.
AUTORES
/ AUTHORS: - Cotterell AA; Kenyon NS
INSTITUCIÓN
/ INSTITUTION: - Diabetes Research Institute, University of
Miami School of Medicine, 1450 N.W. 10th Avenue, Miami, FL 33136,
USA. acottere@med.miami.edu
RESUMEN
/ SUMMARY: - Although intensive insulin therapy has
resulted in improved metabolic control and decreases in the incidence of
complications, the occurrence of severe hypoglycemia remains an issue, as does
the continued potential for complications. Islet transplantation, a promising
treatment for type I diabetes, has been shown to improve blood sugar levels and
decrease or even abrogate the incidence of hypoglycemia. The lack of tissue
availability and the toxic effects of immunosuppressants, however, limit the application
of islet transplantation as a cure for diabetes. This article discusses
possible alternatives to immunosuppressive drugs in human islet
transplantations. N.
Ref:: 68
----------------------------------------------------
[185]
TÍTULO / TITLE: - Tailoring
immunosuppressive therapy for renal transplant recipients.
REVISTA
/ JOURNAL: - Pediatr Transplant 2001 Dec;5(6):467-72.
AUTORES
/ AUTHORS: - Vanrenterghem YF
INSTITUCIÓN
/ INSTITUTION: - Department of Nephrology, University
Hospital Gasthuisberg, Leuven, Belgium. yves.vanrenterghem@uz.kuleuven.ac.be
RESUMEN
/ SUMMARY: - During the past decade several new potent
immunosuppressive agents with different modes of action and different side-effect
profiles have become available. Nowadays immunosuppression after renal
transplantation is no longer one single regimen applicable to all patients. In
the selection of the optimal immunosuppressive protocol, individual
drug-related toxicity, recipient-related risk factors as well as donor organ
characteristics have to be taken into account. This article will give an
overview of the most recently developed immunosuppressive agents available for
clinical use. Their individual mode of action and their different efficacy and
safety profile will be described as basis for selection of each of these drugs
in an attempt to tailor the optimal therapeutic regimen for the individual
patient both in terms of short-term and long-term outcome. N. Ref:: 34
----------------------------------------------------
[186]
TÍTULO / TITLE: - Hypertensinogenic
mechanism of the calcineurin inhibitors.
REVISTA
/ JOURNAL: - Curr Hypertens Rep 2002 Oct;4(5):377-80.
AUTORES
/ AUTHORS: - Curtis JJ
INSTITUCIÓN
/ INSTITUTION: - University of Alabama at Birmingham,
Division of Nephrology, 35294-0006, USA. jcurtis@nrtc.uab.edu
RESUMEN
/ SUMMARY: - Kidney transplantation has seen a
remarkable improvement in allograft survival rates and patient survival rates,
and an equally remarkable reduction in acute rejection rates. Most attribute
these changes to the introduction and widespread use of calcineurin inhibitors
as part of the standard immunosuppressive regimen. Cyclosporine and tacrolimus
are ideal immunosuppressive agents, much more effective and safe than the
previous agents used. Especially ironic, however, for those caring for kidney
transplant patients has been the finding that these breakthrough agents are
toxic to the kidney and can cause hypertension. We can protect the transplanted
kidney from rejection, but still damage it paradoxically by the protecting
agent. Moreover, the prevalence of hypertension in transplant clinics has
increased (from 40%-50% to up to 90%-100%) as these newer agents have gained
widespread use. We remain uncertain of the mechanism whereby these agents cause
hypertension, and therefore remain uncertain of the ideal treatment; however,
the search for a mechanism has taken us from the organ level to intracellular
effects of the agents. The fact that both agents cause nephrotoxicity suggests
that a renal mechanism is at the heart of the hypertension. N. Ref:: 31
----------------------------------------------------
[187]
TÍTULO / TITLE: - Review of the proliferation
inhibitor everolimus.
REVISTA
/ JOURNAL: - Expert Opin Investig Drugs 2002
Dec;11(12):1845-57.
AUTORES
/ AUTHORS: - Nashan B
INSTITUCIÓN
/ INSTITUTION: - Klinik fur Viszeral- und
Transplantationschirurgie, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse
1, D-30625 Hannover, Germany. nashan@tx-amb.mh-hannover.de
RESUMEN
/ SUMMARY: - Everolimus (Certican) is being developed
for prevention of acute and chronic rejection of solid organ transplants. A
novel proliferation inhibitor, everolimus synergies with cyclosporine to
prevent and reverse acute rejection in preclinical models of kidney, heart or
lung transplantation. The manifestations of chronic rejection that may
contribute to graft loss are also inhibited by everolimus in preclinical
models. Although everolimus is metabolised by the cytochrome P450 CYP3A
isoenzyme, coadministration with cyclosporine does not alter the
pharmacokinetics of cyclosporine, but cyclosporine coadministration increases
exposure to everolimus. Everolimus interacts with inhibitors and inducers of
this system; its clearance is reduced in patients with hepatic impairment. In
an immunosuppressive regimen with cyclosporine microemulsion formulation and
corticosteroids, transplant recipients treated with everolimus show low rates
of acute rejection and, in one heart and one renal trial, lower rates of
cytomegalovirus infection. Acute rejection rates are lower than those seen with
azathioprine in cardiac transplant recipients and similar to those seen with
mycophenolate mofetil in renal transplant recipients. Low rates of acute
rejection are maintained when everolimus is given as part of a quadruple
immunosuppressive regimen with low-dose cyclosporine in renal transplant recipients,
with the added benefit of better renal function compared with full-dose
cyclosporine. Use of C(2) monitoring to optimise cyclosporine exposure and
enhance efficacy and safety of everolimus is planned in future studies.
Hypertriglyceridaemia and hypercholesterolaemia have been associated with
everolimus, but these effects are not dose-limiting. There is no clear upper
therapeutic limit of everolimus. However, thrombocytopenia occurs at a rate of
17% at everolimus trough serum concentrations above 7.8 ng/ml in renal
transplant recipients. There are limited safety data available in patients with
trough concentrations > 12 ng/ml. Studies suggest everolimus targets primary
causes of chronic rejection by reducing acute rejection, allowing for cyclosporine
dose reduction (which may lead to improved renal function relative to full-dose
cyclosporine) and by reducing cytomegalovirus infection and inhibiting vascular
remodelling. N.
Ref:: 65
----------------------------------------------------
[188]
TÍTULO / TITLE: - Immunosuppressive
effects of beta-herpesviruses.
REVISTA
/ JOURNAL: - Herpes 2003 May;10(1):12-6.
AUTORES
/ AUTHORS: - Boeckh M; Nichols WG
INSTITUCIÓN
/ INSTITUTION: - Fred Hutchinson Cancer Research Center,
University of Washington, Seattle, WA, USA. mboeckh@fhcrc.org
RESUMEN
/ SUMMARY: - Immunomodulatory effects of human
beta-herpesviruses have been reported in vitro and in vivo. Clinical studies
suggest that beta-herpesvirus infection may increase the risk for other
infections, the severity of infection, or the tempo of disease progression. An
increased incidence of bacterial and fungal infections, and graft rejection,
have been reported in association with cytomegalovirus (CMV), and human herpesviruses
type 6 and type 7 infections have been implicated as risk factors for CMV
infection and graft rejection. Beta-herpesviruses may also interact with HIV-1
and hepatitis C. To prove a causal relationship between beta-herpesviruses and
specific clinical outcomes, randomized trials, with selective suppression of
the virus, are required. Such trials have been performed for CMV and showed a
reduction in bacterial and fungal infections as well as rejection in selected
solid organ transplant recipients. More trials are needed to evaluate whether
the effects seen in observational studies are truly related. N. Ref:: 61
----------------------------------------------------
[189]
TÍTULO / TITLE: - Eleven years
intraoperative ATG bolus. A list of successes.
REVISTA
/ JOURNAL: - Ann Transplant 2002;7(3):4-10.
AUTORES
/ AUTHORS: - Kaden J
INSTITUCIÓN
/ INSTITUTION: - Friedrichshain Hospital, Berlin, Germany.
RESUMEN
/ SUMMARY: - Induction therapy for organ
transplantation using monoclonal antibodies has been in recent years
reevaluated. Results from various centers indicate the value of such therapy,
especially in sensitized patients undergoing kidney transplantation as well as
in simultaneous kidney—pancreas transplant patients. Author presents the
experience of eleven years of intraoperative ATG bolus administration in the
Berlin—Friedrichshain Kidney Transplantation Center. N. Ref:: 43
----------------------------------------------------
[190]
TÍTULO / TITLE: - Immunosuppressive
effect of polycyclic aromatic hydrocarbons by induction of apoptosis of pre-B
lymphocytes of bone marrow.
REVISTA
/ JOURNAL: - Acta Medica (Hradec Kralove)
2002;45(4):123-8.
AUTORES
/ AUTHORS: - Novosad J; Fiala Z; Borska L; Krejsek J
INSTITUCIÓN
/ INSTITUTION: - Charles University in Prague, Faculty of
Medicine in Hradec Kralove, Czech Republic. ukia@fnhk.cz
RESUMEN
/ SUMMARY: - Polycyclic aromatic hydrocarbons (PAH) are
ubiquitous environmental pollutants, distinguished by genotoxic, hepatotoxic,
nephrotoxic and immunotoxic effects. Especially secondary toxicity after
bioactivation by microsomal monooxygenases (dependent on cytochromes P450) is
characteristic of them. The immunotoxic effect is the result of very global
impact on immunological reactivity of an organism and immunosuppression by
induction of apoptosis of pre-B lymphocytes represents one of its particular
forms. It has been proved that the effect of PAH is caused mostly by the
following mechanisms: enzymatic induction by the way of activation of AhR
(Aromatic hydrocarbon Receptor); alteration of cellular DNA; development of
oxidative stress; increase in the concentration of intercellular calcium and
decline of activity of NF-kappaB (Nuclear Factor-kappa B). Most sensitive to
these changes are particularly B-lymphocytic precursors and pre-B lymphocytes.
Intensity of entire manifestations is also considerably dependent on the
presence and intensity of mechanisms of active or passive resistance of cells. N. Ref:: 40
----------------------------------------------------
[191]
TÍTULO / TITLE: - An update in transplant
immunosuppressive therapy.
REVISTA
/ JOURNAL: - Med Health R I 2002 Apr;85(4):131-3.
AUTORES
/ AUTHORS: - Thursby MA; Yango AF; Gohh RY
INSTITUCIÓN
/ INSTITUTION: - Rhode Island Hospital, Division of Renal
Diseases, 593 Eddy Street, Providence, RI 02903, USA. Mthursby@lifespan.org N. Ref:: 10
----------------------------------------------------
[192]
TÍTULO / TITLE: - Immunosuppression in
liver transplantation.
REVISTA
/ JOURNAL: - Minerva Chir 2003 Oct;58(5):725-40.
AUTORES
/ AUTHORS: - Everson GT; Trotter JF; Kugelmas M; Forman
L
INSTITUCIÓN
/ INSTITUTION: - Division of Gastroenterology and
Hepatology and Department of Medicine, University of Colorado School of
Medicine, Denver, CO 80262, USA. greg.overson@uchsc.edu
RESUMEN
/ SUMMARY: - This article highlights the currently
available immunosuppressive medications that are used to prevent or treat
hepatic allograft rejection. Currently-available immunosuppressive medications
are highly effective in prevention of allograft rejection, graft loss, and
patient death. However, side effects of medications are common, usually dose-related,
and specific to the administered drug. Maintenance immunosuppression which has
been primarily based upon calcineurin inhibitors (Cyclosporine, CsA, or
tacrolimus, Tac) is commonly modified to reduce metabolic complications of
therapy. Toxic consequences of steroids may be ameliorated by steroid
withdrawal without risk of acute rejection or immunologic graft loss.
Calcineurin-sparing regimens may include use of mycophenolate mofetil (MMF) or
sirolimus, and allow reduction in doses and plasma levels of CsA and Tac.
Recurrence of hepatitis C is universal after liver transplantation and
progresses rapidly, compared to its natural history in non-immunocompromised
patients. Unfortunately, no single immunosuppressive agent or strategy has yet
been shown to convincingly modify the course of post-transplant recurrence.
Most centers manage recurrenc hepatitis C by either steroid avoidance,
reduction in immunosuppression, or institution of antiviral therapy. Ongoing
advances in immunosuppressive and antiviral medications will allow tailoring of
the immunosuppressive prescription, which undoubtedly will benefit current and
future liver recipients. N.
Ref:: 88
----------------------------------------------------
[193]
TÍTULO / TITLE: - Sepsis and
treatment-induced immunosuppression in the patient with cancer.
REVISTA
/ JOURNAL: - Crit Care Nurs Clin North Am 2003
Mar;15(1):109-18.
AUTORES
/ AUTHORS: - Reigle BS; Dienger MJ
INSTITUCIÓN
/ INSTITUTION: - College of Nursing, University of
Cincinnati, 3110 Vine Street, Cincinnati, OH 45221-0038, USA. reiglebs@uc.edu
RESUMEN
/ SUMMARY: - Treatment for cancer is frequently an
assault to the immune system. The immunosuppression that results significantly
increases the patient’s risk for infection. In this patient population,
infection can quickly progress to sepsis, septic shock, and death. A high index
of suspicion during nursing assessments is a critical strategy in early
identification of infections. In addition, judicious adherence to infection
control measures, appropriate use of prophylactic agents, and immediate
employment of broad-spectrum antibiotics that are empirically based are
essential strategies to maximize the patient’s likelihood for survival. N. Ref:: 36
----------------------------------------------------
[194]
TÍTULO / TITLE: - Review of the
properties and mechanisms of action of cyclosporine with an emphasis on
dermatological therapy in dogs, cats and people.
REVISTA
/ JOURNAL: - Vet Rec 2003 Jun 21;152(25):768-72.
AUTORES
/ AUTHORS: - Robson D
INSTITUCIÓN
/ INSTITUTION: - Melbourne Veterinary Referral Centre, 70
Blackburn Road, Glen Waverley, Victoria 3150, Australia.
RESUMEN
/ SUMMARY: - Cyclosporine is being increasingly used in
veterinary medicine. It is a potent suppressor of T cell induction and
proliferation, and has a wide variety of anti-inflammatory and
antiproliferative effects, downregulating effects on antigen presentation, and
variable effects on parasites. This paper reviews its properties and mechanisms
of action with particular reference to its use in the treatment of
dermatological conditions in dogs, cats and people. N. Ref:: 46
----------------------------------------------------
[195]
TÍTULO / TITLE: - Molecular mechanisms of
the immunosuppressive effect of erythroid cells.
REVISTA
/ JOURNAL: - Russ J Immunol 2002 Oct;7(3):211-8.
AUTORES
/ AUTHORS: - Kozlov VA
INSTITUCIÓN
/ INSTITUTION: - Institute of Clinical Immunology, Siberian
Branch of RAMS, Yandritsovskaya str. 14, Novosibirsk-99 630099, Russia. v_kozlov@online.nsk.su
RESUMEN
/ SUMMARY: - This review presents data suggesting a new
immunoregulatory role of the erythroid nucleus-containing cells. The three main
mechanisms of the possible immunosuppressive effect of these cells are
described. It has been demonstrated that the erythroid nucleus-containing cells
produce a variety of both pro- and anti-inflammatory cytokines. The p15 protein
(a product of the env gene) is considered to provide a novel immunosuppressive
mechanism. Finally, the existing data suggest that the erythroid
nucleus-containing cells are able to produce an immunosuppressive factor, which
is different from the known cytokines. It has been proposed that the immunosuppressive
effect of the erythroid nucleus-containing cells greatly contributes to the
regulation of the immune homeostasis in normal and immunopathological
conditions. N. Ref:: 33
----------------------------------------------------