Transplantation
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Israel's rates of organ donation have been one of the lowest among developed countries. An attempt to change this has led to the introduction of a pioneering new law, the Organ Transplant Act 2008, which came into effect in January 2010 and sets out principles underlying a new policy in relation to the allocation of organs for transplantation. ⋯ In this opinion piece, we argue that although this approach merits attention for its innovative aspects and its potential benefits, it raises some ethical difficulties. In particular, we discuss some problems of justice and fairness inherent in the system, focusing on inequalities because of the (a) number of relatives one might have, (b) the type of living donation one makes, (c) the potential for strategic behavior, and (d) problems regarding the consent of family members.
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Transplant arteriosclerosis is a major cause of late intestinal allograft dysfunction. However, little is known about the immunologic and molecular mechanisms underlying it, and no effective treatment is available. This study aimed to investigate the role of sphingosine kinase 1 (SPHK1)/sphingosine-1-phosphate (S1P) in transplant arteriosclerosis and find out whether fish oil (FO) attenuates allograft arteriosclerosis through S1P signaling. ⋯ These results demonstrate that the activation of SPHK1/S1P signaling plays a possible role in the pathogenesis of transplant arteriosclerosis. The reduction of allograft arteriosclerosis by FO may be associated with down-regulation of SPHK1/S1P signaling. Understanding the role of FO for SPHK1/S1P may help us to identify considerable therapeutic targets for transplant arteriosclerosis.
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Review
Immunological issues in clinical composite tissue allotransplantation: where do we stand today?
Composite tissue allografts are made of histogenetically different tissues and although skin seems to be the most antigenic of them, it is unknown whether the dominant immune response is really directed against the skin or we have insufficient information on the involvement of the other components of these allografts. The first clinical signs of acute rejection manifest on the skin and microscopically the earliest lesions consist in a dermal perivascular lymphocytic infiltrate, predominantly made of CD3+/CD4+ T cells. On the basis of the histological changes, a specific score (Banff score 2007) has been established to assess the severity of rejection. ⋯ The complications in composite tissue allotransplantation are similar to those usually reported after solid organ transplantation and have prompted different strategies to minimize the maintenance immunosuppression or to induce donor-specific tolerance. Furthermore, to what extent the immunosuppression can be tapered is unknown, as well as the influence of donor bone-marrow infusion in tolerance and chronic rejection. The increasing number of patients and the longer follow-up hopefully will allow answering these questions.
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Remote ischemic preconditioning (RIPC) protects against liver ischemia reperfusion (IR) injury. An essential circulating mediator of this protection is nitric oxide (NO) induced by lower limb RIPC. One of the mechanisms through which NO generally acts is the soluble guanylyl cyclase-cyclic GMP (sGC-cGMP) pathway. The present study aimed to assess the role of hepatic sGC-cGMP in lower limb RIPC-induced protection against liver IR injury. ⋯ The hepatic sGC-cGMP pathway is required for mediating the protective effects of lower limb RIPC on hepatic MBF in liver IR injury.
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The introduction of generic immunosuppressant medications may present an opportunity for cost savings in solid organ transplantation if equivalent clinical outcomes to the branded counterparts can be achieved. An interprofessional working group of the Canadian Society of Transplantation was established to develop recommendations on the use of generic immunosuppression in solid organ transplant recipients (SOTR) based on a review of the available data. Under current Health Canada licensing requirements, a demonstration of bioequivalence with the branded formulation in healthy volunteers allows for bridging of clinical data. ⋯ The advent of generic immunosuppression will require new practices including more frequent therapeutic drug and clinical monitoring, and increased patient education. The additional workload placed on transplant centers without additional funding will create challenges and could ultimately jeopardize patient outcomes. Until more robust clinical data are available and adequate regulatory safeguards are instituted, caution in the use of generic immunosuppressive drugs in solid organ transplantation is warranted.