Browsing by Subject "Transplantation"
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- PublicationOpen AccessBirth defects in juvenile Wistar rats after exposure to immunosuppressive drugs during pregnancy(Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Kabat Koperska, Joanna; Kolasa Wołosiuk, Agnieszka; Pilutin, Anna; Safranow, Krzysztof; Kosik Bogacka, Danuta; Baranowska Bosiacka, Irena; Gołembiewska, Edyta; Kędzierska, Karolina; Domański, Leszek; Ciechanowski, KazimierzIntroduction: Immunosuppressive drugs and their active metabolites can cross the placental barrier and enter fetal circulation. The adverse effects on the fetus include chromosomal aberrations, structural malformations, organ-specific toxicity and intrauterine growth retardation. The aim of our study was to investigate the impact of “safe” and “contraindicated” immunosuppressive drugs on birth defects in juvenile Wistar rats after exposure of pregnant female rats to these drugs. Material and methods: The study was conducted on 32 female Wistar rats, subjected to immunosuppressive regimens most commonly used in therapy of human kidney transplant recipients. The animals received drugs by oral gavage 2 weeks before pregnancy and during 3 weeks of pregnancy. Results: Treatment with mycophenolate mofetil and everolimus turned out to be toxic. We have noticed a significantly reduced number of live births in all pregnant rats exposed to these drugs in combination with calcineurin inhibitors and prednisone. Malformations and histological changes of fetal organs were confirmed after mycophenolate mofetil exposure during pregnancy. Conclusions: Mycophenolate mofetil turned out to be more toxic when used with tacrolimus than with cyclosporin (delivery of live offspring was possible only in the latter group). Everolimus in combination with cyclosporin effectively suppressed the fetal maturation in utero, but did not contribute to the development of malformations.
- PublicationEmbargoClinical features and outcomes of tuberculosis in transplant recipients as compared with the general population: a retrospective matched cohort study(Elsevier, 2015-04-14) Benito, N.; García-Vázquez, Elisa; Horcajada, J. P.; González, J.; Oppenheime, F.; Cofán, F.; Ricart, M. J.; Rimola, A.; Navasa, M.; Rovira, M.; Roig, E.; Pérez-Villa, F.; Cervera, C.; Moreno, A.; MedicinaThere are no previous studies comparing tuberculosis in transplant recipients (TRs) with other hosts. We compared the characteristics and outcomes of tuberculosis in TRs and patients from the general population. Twenty-two TRs who developed tuberculosis from 1996 through 2010 at a tertiary hospital were included. Each TR was matched by age, gender and year of diagnosis with four controls selected from among non-TR non-human immunodeficiency virus patients with tuberculosis. TRs (21 patients, 96%) had more factors predisposing to tuberculosis than non-TRs (33, 38%) (p <0.001). Pulmonary tuberculosis was more common in non-TRs (77 (88%) vs. 12 TRs (55%); p 0.001); disseminated tuberculosis was more frequent in TRs (five (23%) vs. four non-TRs (5%); p 0.005). Time from clinical suspicion of tuberculosis to definitive diagnosis was longer in TRs (median of 14 days) than in non-TRs (median of 0 days) (p <0.001), and invasive procedures were more often required (12 (55%) TRs and 15 (17%) non-TRs, respectively; p 0.001). Tuberculosis was diagnosed post-mortem in three TRs (14%) and in no non-TRs (p <0.001). Rates of toxicity associated with antituberculous therapy were 38% in TRs (six patients) and 10% (seven patients) in non-TRs (p 0.014). Tuberculosis-related mortality rates in TRs and non-TRs were 18% and 6%, respectively (p 0.057). The adjusted Cox regression analysis showed that the only predictor of tuberculosis-related mortality was a higher number of organs with tuberculosis involvement (adjusted hazard ratio 8.6; 95% CI 1.2–63). In conclusion, manifestations of tuberculosis in TRs differ from those in normal hosts. Post-transplant tuberculosis resists timely diagnosis, and is associated with a higher risk of death before a diagnosis can be made.
- PublicationOpen AccessDifferential signaling through the T cell receptor: from biochemistry to transplantation tolerance(Murcia : F. Hernández, 1998) Madrenas, J.; Lazarovits, A.I.Recent advances in our understanding of the structural nature of T cell activation and signal transduction from the T cell receptor for antigen make possible the development of new tolerogenic strategies. Here. we summarize the evidence supporting a critical role for the CO-receptor molecule (CD4 or CD8) and CD45 in determining the pattern of T cell receptormediated signaling. The consequences of this differential signaling can range from T cell proliferation and cytokine production to the establishment of a state of proliferative unresponsiveness known as T cell anergy. Inducing T cell anergy can be an alternative approach for the establishment of transplantation tolerance.
- PublicationOpen AccessOlfactory ensheathing cells: potential for glial cell transplantation into areas of CNS injury(Murcia : F. Hernández, 1995) Doucette, R.Ensheathing cells are the glial cells that ensheath olfactory axons within both the PNS and CNS portions of the primary olfactory pathway. These glial cells express a mixture of astrocyte-specific and Schwann cell-specific phenotypic features, support axonal growth by olfactory as well as by non-olfactory neurons, and survive transplantation into injured areas of the CNS.This review article focuses on those phenotypic features that are expressed by ensheathing cells that make them ideal candidates for transplantation into wound cavities in the damaged spinal cord of humans. Although much work remains to be done before such a therapeutic approach can be tried, the likelihood that ensheathing cells could simultaneously perform the roles of both astrocytes and Schwann cells following transplantation is the justification for developing such a therapeutic approach using animal models of spinal cord injury
- PublicationOpen AccessPluripotent stem cells isolated from umbilical cord form embryonic like bodies in a mesenchymal layer culture(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2015) Tsagias, Nikos; Kouzi-Koliakos, Kokkona; Karagianis, Vasileios; Tsikouras, P.; Koliakos, George G.Recently the matrix of umbilical cord began to use as an alternative source of stem cells additionally to the blood of umbilical cord. Umbilical cord has been used mainly for mesenchymal stem cell banking. The immunological characteristics of mesenchymal stem cells in combination with their ability to avoid rejection make them an attractive biological material for transplantations. In this study the isolation of small in size pluripotent stem cells from umbilical cord expressing early transcription factors with characteristics that resemble to embryonic stem cells is investigated. Pluripotent stem cells were isolated from human umbilical cords, by a new strategy method based on unique characteristics such as the small size and the positivity on early transcription factors OCT and Nanog. An enriched population of CXCR4+ OCT+ Nanog+ CD45- small stem cells from the cord was isolated. This fraction was able to create alkaline phosphatase positive like spheres forms in a mesenchymal layer with multilineage differentiation capacity. Our results were assessed by RT PCR and electophoresis for the pluripotent genes. These data suggest that umbilical cord provides an attractive source not only of mesenchymal stem cells but moreover of pluripotent stem cells. The method described herein should be applied in the field of stem cell banking in addition to the classical umbilical cord harvesting method. Isolation of a population of cells with pluripotent characteristics from umbilical cord. Adoption of a second centrifugation step for the pluripotent stem isolation. Increasing the value of the cord and explaining the pluripotency. This work will enhance the value of umbilical cord harvesting.
- PublicationOpen AccessThe effect of immunosuppressive therapy on renal cell apoptosis in native rat kidneys(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2015) Kędzierska, Karolina; Sporniak-Tutak, Katarzyna; Kolasa, Agnieszka; Domański, Leszek; Domański, Maciej; Sindrewicz, Krzysztof; Smektała, Tomasz; Bober, Joanna; Safranow, Krzysztof; Osękowska, Bogumiła; Kabat-Koperska, Joanna; Baranowska-Bosiacka, Irena; Parafiniuk, Mirosław; Urasińska, Elżbieta; Ciechanowski, KazimierzAim: To analyse the impact of the most commonly used immunosuppressive drugs on the occurrence of apoptosis in the native kidneys of Wistar rats. Method: The study involved 36 rats. The animals grouped according to the immunosuppressive regimen used (tacrolimus, mycophenolate mofetil, cyclosporine A, rapamycin and prednisone). The rats in all study groups were treated with a 3-drug protocol for 6 months. The medication dose was adjusted based on available literature data. No drugs were administered to the control group. The rats were then killed. Autopsies of all animals were performed and the kidneys were isolated for histopathology (HE + PAS). To assess cell apoptosis the TUNEL reaction was performed. Blood trough levels of immunosuppressive drugs as well as the parameters of peripheral blood were determined. Results: 1. In rats treated with cyclosporine A distal nephron tubules were characterised by more pronounced apoptosis. 2. In tacrolimus-treated rats a lower intensity of apoptosis was found in the distal tubules. 3. In rapamycin-treated rats the apoptosis was inhibited both in the distal and proximal nephron tubules. 4. In MMF treated rats intense apoptosis was observed in the proximal nephron tubules. 5. There were no significant changes in renal histopathology (HE + PAS). Conclusions: The apoptosis in nephron tubules caused by immunosuppressive therapy is not accompanied by any histopathological changes (eg fibrosis, inflammation, tubular atrophy, vacuolation of the tubular cells) in light microscopy