ORGAN TRANSPLANT

Author: MILLAN LÓPEZ OLGA.
Year: 2003.
University: BARCELONA [www.ub.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA.

Summary: The use of immunosuppressant in the transplantation therapies requires indefinite. The pharmacokinetic parameters, although they are very useful especially in the prevention of toxicity, are not enough to show any interindividual variability exist, or to know  What level of immunosuppression need a particular patient? Neither  What level of immunosuppression is obtained with drugs that are administered? In útlimos years have launched a series of studies focusing on knowledge of the biological impact conducting these drugs in the recipient's immune system is what is known as Pharmacodynamics. Pharmacokinetics and Farmacodinamia are two disciplines that are complementary; us define a destination of the drug while the other defines us the effect of doses administered. In recent years, various methods have been proposed in order to evaluate more effectively the action of immunosuppressive: 1-To assess the activity of the target enzyme immunosuppressive issue. 2-evaluate some mediator involved in the mechanism of action. 3-To evaluate collateral markers induced by immunosuppressants. The aim of the thesis was to support pilot on the assumption that the extent of the activity of the target enzyme for certain immunosuppressive is a useful tool to highlight shortfalls in immunosuppression. We have developed a whole series of methods pharmacodynamic evaluated on the basis of the drug: Mycophenolate Mofetil (MMF) (Activity enzyme IMPDH, Response EMC), cyclosporine (CsA) and Tracrolimus (TRL) (Activity phosphatase calcineurin, production of IL-2 and IFN - gamma), and has done a thorough monitoring both pharmacokinetic and pharmacodynamic populations in renal transplant patients in the maintenance phase as a population infected with Human Immunodeficiency Virus (HIV). The results focus on 3 articles published: Clinical Chemistry, 2000, 46:9; 1376; Clinical Chemistry, 2003; 49:11; 1891 and Clinical Pharmacokinetics 2003, in press and some data submitted for publication. For the monitoring of treatment with MMF pharmacodynamic parameters Response EMC, designed by our group has been more effective than assessing their target specific enzyme IMPDH, given the high variability that I am presenting this argument. The assessment of the activity calcineurin is valid for tracking delt ratamiento immunosuppressive with monotherapies based on the administration CsA or TRL, but when these drugs anticalcineurínicos are used concomitantly with MMF parameter that best reflects the joint action of these drugs is the assessment production IL-2. When evaluated the efficacy of low dose of MMF in patients infected with HIV, the only parameter Response EMC was able to differentiate those patients who rebotaban in viral load following the abolition of antiretroviral treatment which does not respect the rebotaron. The Farmacodinamica along with the Pharmacokinetics are essential for progress in the knowledge of immunosuppressive treatment. Using both disciplines could optimize the introduction of new drugs, new partnerships and new dosing schedules.

Author: GONZÁLEZ LEÓN LETICIA.
Year: 2004.
University: COMPLUTENSE DE MADRID [www.ucm.es].
Place of defense: FACULTAD DE VETERINARIA.
Place of preparation: FACULTAD DE VETERINARIA.

Summary: The knowledge of the molecular basis of a large number of pathologies makes stem cells are an excellent target for gene therapy. The characteristics of these cells ensure that the genes transferred to a small population of cells can correct the genetic damage. This remains a key objective for many researchers. The need for a model pre-clínico in large animals that can address these therapies has been to use the dog for these purposes because it has a diversity comparable to the human gene. Based on these assumptions we made it our goal particular gene transfer to a population of precursors hempatopoyéticos canines, a marker gene, in our case the gene coding for green fluorescent protein. Because studies transduction of human hematopoietic cells are not sufficiently sophisticated for its application in gene therapy protocols, and the optimization of large animals would be useful for therapeutic purposes. These goals have been divided into three sub-targets. * Asilamiento, characterization and identification of a population of hematopoietic precursors canines. * Evaluation of the ability of people enriched hematopoietic stem cells, to nest, proliferate and differentiate themselves: putting a focus on the studies functionality progeny provenida. * Lastly, optimize the preconditions and test different protocols gene transfer until a suitable percentage of cells transducidas allowing us to, in subsequent studies, monitoring of animal Chimerism and tackling diseases through gene therapy. We obtained results which are summarized in the following conclusions. * The antibody 6C9 joins two distinct populations, of which only one of them has a characteristic size and complexity of immature cells. The lack of enrichment in hematopoietic progenitors in the population "6C9 +" suggests that for the moment, this antibody is not a suitable tool for the purification and isolation of hematopoietic progenitors canines. * The use of anticerupos monoclonal cell lineage - specific positive canine, has allowed us to obtain a population Lin-enriquecida cell CD34 + and Rh-123 low. The increase in erythroid progenitors mielomonocíticos and in this population has diso quantified by cultured clonogénicos and morphological studies. * This paper describes for the first time the in vitro generation of neutrophils canines, with the ability to reach pockets of infection and ensure the defense mechanisms against infections unspecified. All the results obtained with our in vitro model, assures us the ability to repopulation of the population Lin-; requirements essential to ensure the success of transplants of hematopoietic stem cells. * High percentages of transucción obtained in hematopoietic progenitors canines should be attributed mainly to the specificity of the canine cytokines, and the development of a protocol transduction which is characterized by an increase in the number of viral particles on the layer fironectina and the asuencia contact between viral supernatant and the target cells. In response to the overall objective of this thesis, we believe that the contributions described in this report contributing to the establishment and progress of a model pre-clínico in large animals, which is essential today for the development and implementation of expectant treatment protocols.

Author: MORELL GINESTÀ MIREIA.
Year: 2004.
University: BARCELONA [www.ub.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA.

Author: CABALLERO FLORES FRANCISCO.
Year: 2004.
University: AUTÓNOMA DE BARCELONA [www.uab.es].
Place of defense: FACULTAD DE MEDICINA-DEPARTAMENTO DE MEDICINA-UAB.
Place of preparation: UNIVERSIDAD AUTONOMA DE BARCELONA.

Summary: INTRODUCTION In the works that constitute this thesis reflects the broader criteria for acceptance of donor organs for transplantation and at the global level as well as our experience with all cases of organ transplants performed with abdominal and thoracic grafts from donors of organs killed by drug use (cocaine, ecstasy) contracts without parenteral and methanol. The transplantation of organs from these donors is little documented in the literature. OBJECTIVES 1-Analyze all the strategies adopted by our group to increase the number of donors and viable human organs for transplantation. 2-Establish the criteria for evaluating structural and functional and viability of all organs for transplantation generated by deceased donors acute for certain drugs, gas, drug abuse and products for industrial use and domestic. 3, - evaluate our results with 52 patients transplanted with 54 bodies (37 kidneys, 9 livers, 5 hearts, 2 lungs and 1 pancreas) from 20 deceased donors acute (16 by methanol, 2 ecstasy and 2 for cocaine) : graft survival and receiver in the short, medium and long term. CONCLUSIONS 1 - The percentage of corpses in encephalic death and beating heart that do not meet the criteria for donation of organs for transplant, because of contraindications for the donation or for the use of specific organs, can be less than 7.5 %. 2 - There is no age limit for the donation of organs for transplantation. A 33% of total organ donors can be older than 65 years of age and can represent from an epidemiological point of view one of the most important factors that determines the number of transplants of livers and kidneys. 3 - The actuarial survival of kidney graft single donor 60-87 years of age recipients older than 60 years has been 87% and 81% a year and 5 years of transplantation, respectively. When recipients were younger than 60 years old kidney graft survival was 95% and 83%, respectively. 4 - There is a direct correlation between the donor's age and cause of his death with the number of transplanted organs and generated. Of the donors younger than 50 years are extracted and transplanted organs that most of those older than 50 years, especially those of deceased donors by head trauma and subarachnoid hemorrhage. Of the donors older than 50 years are discarded post-extracción more organs for transplants from donors that young people, especially those from deceased donors by anoxia encefálica secondary to primary cardiac arrest by micardiopatía ischemic. 5, real-Donors of organs may be effective not less than 13%. They tend to be donors older than 65 years of age who have a higher incidence of injuries or structural arterial and parenchymal severe cancer not previously diagnosed. Generally kidney and prostate. 6 - The survival of the graft and recipient of the heart, liver and kidneys in the short and long term with bodies of deceased donors by methanol poisoning is similar to that of the rest of transplants with organs from donors who are not intoxicated. 7-thoracic and abdominal organs from deceased donors acute ecstasy may be valid for transplantation, and the evolution of transplants in the short and medium term strictly normal. 8-transplant liver and kidneys with organs from deceased donors by acute cocaine intoxication can have an evolution of graft and recipient strictly favorable. 9, - The transmission of toxic and its toxic effects through the transplanted organ from donor to recipient, is exceptional.

Author: MONFORTE TORRES VÍCTOR.
Year: 2004.
University: AUTÓNOMA DE BARCELONA [www.uab.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: ESCUELA DE POSTGRADO.

Author: GALLEGO VALADÉS FRANCISCA.
Year: 2004.
University: AUTÓNOMA DE BARCELONA [www.uab.es].
Place of defense: HOSPITAL DE LA SANTA CREU I SANT PAU.
Place of preparation: ESCUELA DE POSTGRADO.

Summary: We analyzed the effect of IL-12 on the autoimmune disease in a mouse model semialogénico of chronic graft versus host the (EICHc) induced in mice (Balb / cAA / J) F1 (CAF1) intraperitoneally injected via cell semialogénicas the parent strain BALB / c. IL-2 was administered 1 hour prior to the transplantation of cells semialogénicas in two different protocols Management: A-injected 2ug of rmIL-12 (IL-12 murine recombinant) per mouse before the first injection of cells semialogénicas. B-Inyectado the 2 ug of rmIL-12 divided into 5 days. There was a response Th1 but not acute illness appeared in the EICH despite differences in class I and II antigens increased histocompatibility complex (MHC) between donor and recipient. Four days after the transfer of cells semialogénicas, mice treated with rmIL-12 showed a marked reduction in the percentage of B cells compared with animal control CAF1 and mice with EICH CAF1 + BALB / c. After 5-6 months of tracking the disease, the animal Chimerism of donor cells significantly increased in spleen (70 +-31 vs 43 +-31%) and thymus. The flow cytometry showed splenocytes of the quimierismo cell which was formed by donor T lymphocytes CD4 T CD8 yBy percentages were higher in animals injected with IL-12. In addition, 100% of T lymphocytes CD8 were home donor animals with EICH treated with IL-12 and 50% were of donor origin in animals with EICH untreated. The results showed that: 1-IL-12 probably played a role in the mechanism of cell donor animal Chimerism probably produced by mechanisms mediated by CTL donors anti-huésped. 2, Non-variant induces acute EICH despite the differences in class I and II MHC molecules. 3-IL-12 did not show any effect on clinical signs of disease AR-like developed in this model EICH although subclinical histological signs were less frequent, and was not detected in mice with glomerulonephritis EICH treated with IL-12.