1,721,092 research outputs found
Xenotransplantation, where do we stand?
No full textXenotransplantation is currently being investigated as a possible solution to the world-wide shortage of human organs. Several major advances have unquestionably been accomplished in the last decade in this field. These include an elucidation of the immunological mechanisms underlying the rejection of pig organs transplanted into primates, the generation of novel lines of genetically-engineered pigs that are more "compatible" with man and a better understanding of the risk of zoonosis related to the transmission of porcine endogenous retroviruses to primates. Though very encouraging, the existing preclinical data do not entitle clinical trials with pig organs to begin as yet and, for the time being, the use of human organs remains the only viable option for patients with terminal organ failure
Current challenges in xenotransplantation
Full text linkPurpose of review: In recent years, the xenotransplantation science has advanced tremendously, with significant strides in both preclinical and clinical research. This review intends to describe the latest cutting-edge progress in knowledge and methodologies developed to overcome potential obstacles that may preclude the translation and successful application of clinical xenotransplantation. Recent findings: Preclinical studies have demonstrated that it is now possible to extend beyond two years survival of primate recipients of life saving xenografts. This has been accomplished thanks to the utilization of genetic engineering methodologies that have allowed the generation of specifically designed gene-edited pigs, a careful donor and recipient selection, and appropriate immunosuppressive strategies.In this light, the compassionate use of genetically modified pig hearts has been authorized in two human recipients and xenotransplants have also been achieved in human decedents. Although encouraging the preliminary results suggest that several challenges have yet to be fully addressed for a successful clinical translation of xenotransplantation. These challenges include immunologic, physiologic and biosafety aspects. Summary: Recent progress has paved the way for the initial compassionate use of pig organs in humans and sets the scene for a wider application of clinical xenotransplantation
ZIGOMICOSI SISTEMICA IN UNA MACACA FASCICULARIS XENOTRAPIANTATA DI RENE
No full textUna Macaca fascicularis, sottoposta a nefrectomia bilaterale, ha ricevuto un trapianto di rene da suino transgenico. 15 giorni dopo il trapianto, il primate ha evidenziato un quadro clinico compatibile con insufficienza renale: edema generalizzato con incremento del 20% del peso e aumento dei parametri ematici di funzionalità renale, associati a marcata neutrofilia. 19 giorni post-trapianto, l’animale è stato sottoposto a eutanasia per insufficienza renale e deterioramento delle condizioni generali. L’esame necroscopico ha evidenziato, oltre a rigetto d’organo, edema sottocutaneo diffuso, materiale purulento in corrispondenza della ferita chirurgica, effusione emorragica addominale, aree puntiformi biancastre su fegato, peritoneo, pancreas e sierosa intestinale e linfadenopatia meseraica. L’esame istologico della ferita chirurgica ha evidenziato pannicolite e miosite, piogranulomatose e settiche, focalmente estese, con estesa steatonecrosi, trombosi e reazione da corpo estraneo (filo di sutura) con funghi intralesionali e intravascolari. L’esame istologico della cavità addominale ha evidenziato peritonite e sierosite intestinale, purulente con trombosi, funghi intralesionali e invasione vascolare e linfonodale; peritonite granulomatosa, con reazione da corpo estraneo (filo di sutura); pancreatite, purulenta e necrotizzante, con funghi intralesionali ed emboli fungini.
In base alle caratteristiche morfologiche, la diagnosi eziologica è di zigomicosi cutanea, sistemica ed embolica.
La zigomicosi nell’uomo si osserva in soggetti immunocompromessi, con recente aumentata incidenza tra i riceventi di trapianto d’organo. Nell’animale la via d’ingresso è in genere attraverso una ferita cutanea. La malattia non è contagiosa e l’ambiente è la fonte d’infezione. Il reperto più caratteristico è l’invasione dei vasi ematici, del tessuto perineurale e gli infarti tissutali che determinano una malattia sistemica.
Esiste solo un caso descritto di zigomicosi sistemica in Macaca fascicularis, mentre la forma cutanea è stata descritta in altri primati
Xenotransplantation: An Overview of the Field
No full textXenotransplantation, the transplantation of cells, tissues, or organs between different species, has the potential to overcome the current shortage of human organs and tissues for transplantation. In the last decade, the progress made in the field is remarkable, suggesting that clinical xenotransplantation procedures, particularly those involving cells, may become a reality in the not-too-distant future. However, several hurdles remain, mainly immunological barriers, physiological discrepancies, and safety issues, making xenotransplantion a complex and multidisciplinary discipline. © 2012 Springer Science+Business Media, LLC
[Role of antibodies in kidney transplant]
No full textRejection is one of the most frequent causes of graft loss after a kidney transplant. In this context, in the last few years the essential role of antibodies in the anti-graft immune response has become more evident. Antibody-mediated damage has been classified into four histological patterns: hyperacute rejection, caused by the presence of pre-existing donor-specific antibodies directed against HLA or non-HLA antigens; acute antibody-mediated rejection, usually due to antibodies elicited following transplantation; chronic antibody-mediated rejection, which can develop months or years after the first appearance of circulating antibodies; and Cd4 deposition without morphologic evidence of active rejection, previously described as ''accommodation''. In recent years, thanks to the development of specific desensitization protocols, it has become possible to transplant patients sensitized to donor HLA antigens. Recently, besides consolidated protocols which include immunoglobulin administration associated or not with plasmapheresis, novel approaches of therapeutic apheresis with specific removal of antibodies and bortezomib, an agent that can efficiently decrease donor-specific antibody levels, have been developed. As far as the treatment of antibody-mediated rejection is concerned, different immunosuppressive strategies have been used. These include the combination of immunoglobulin administration and plasmapheresis with or without the use of an anti-CD20 monoclonal antibody. More recently, an innovative therapy with eculizumab has proved to be very effective against acute antibody-mediated rejection. The debate regarding the cause-effect relationship between the development of an early post-transplant humoral immune response in patients with stable graft function and premature graft loss remains open to discussion. Clinical studies are underway to provide an adequate answer to this question. In conclusion, comprehension of the fundamental role of antibodies and the consolidation of desensitization techniques together with early treatment of antibody-mediated rejection remain important objectives to improve long-term allograft survival
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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