Intestinal Transplantation for Necrotizing Enterocolitis
David J. Hackam in Necrotizing Enterocolitis, 2021
Unlike other transplants where laboratory results can be used to assess graft function and possible rejection, there is no clear marker for intestinal rejection. The gold standard for diagnosing acute intestinal rejection is an allograft mucosal biopsy. The symptoms and signs of ACR are nonspecific and may be due to other nonrejection causes. Hence, especially in the early period, frequent scopes and intestinal allograft biopsies are done until a good baseline is established. Once established, they can be done less frequently and then as clinically indicated. Although yearly scopes are performed for surveillance, these are mostly insufficient to assess for chronic rejection, where a full-thickness biopsy, often with a mesenteric vessel, is needed to assess for vascular intimal hyperplasia that would suggest chronic rejection. Hence, chronic rejection is mostly diagnosed clinically and radiologically and then finally when the allograft, or part thereof, is resected.
Hypersensitivity
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal in Principles of Physiology for the Anaesthetist, 2020
There are four types of HVGR: Hyperacute rejection occurs within minutes of transplantation by interaction of preformed cytotoxic antibodies in the host's circulation with HLA class I antigens expressed on the endothelium of the graft. The result is complement activation, coagulation, microvascular thrombosis and graft infarction.Accelerated rejection occurs within 4 days of transplantation by cellular and humoral mechanisms in recipients who have been sensitized previously against the donor's antigens.Acute rejection is a T-lymphocyte-mediated reaction, which occurs during the first month after transplantation.Chronic rejection is characterized by the slow loss of tissue function over a period of months or years. It may be a cellular immune response, an antibody response or a combination of the two. It is associated with chronic immune-mediated destruction and arteriolar narrowing with ischaemia of the graft.
Complications of Cardiac and Lung Transplantation
Stephen M. Cohn, Matthew O. Dolich in Complications in Surgery and Trauma, 2014
Chronic rejection occurs in the months to years after lung transplantation and is the major limitation to long-term graft survival in lung transplantation. The incidence and severity of chronic rejection is higher than in other solid organs for unclear reasons, possibly due to the direct exposure of the graft to the environment via inhaled air, which differs from other transplanted organs. Chronic rejection manifests in the lungs as bronchiolitis obliterans, which has characteristic chest computed tomography findings of bronchiectasis, mucous plugging, airway wall thickening, mosaic pattern, and air trapping. Functionally, progressive decrease in the forced expiratory volume in 1 s by pulmonary function testing is observed along with graft failure and ultimately recipient demise [34]. Radiographic as well as clinical findings of chronic rejection in the current era affect up to 70% of lung transplant recipients who survive for 5 years.
Lessons from transmissible cancers for immunotherapy and transplant
Published in Immunological Medicine, 2022
Rafael Cardoso Maciel Costa Silva, Carolina Panis, Bruno Ricardo Barreto Pires
Transplant rejection is mediated mostly by the adaptive immune system [3]. There are three main mechanisms by which adaptive immunity is triggered to mediate allogeneic tissue rejection: direct, indirect, and semi-direct [4]. The direct pathway is based on the ability of dendritic cells (DCs) from the donor tissue (or transmissible cancer) to present allopeptides and activate host T cells through a non-self MHC. Around 1–10% of T cells can recognize the complex non-self MHC-peptide and mount a specific immune response [5]. The direct pathway is believed to be the dominant immune response during acute rejection. The ability of non-self MHC to present more than one allopeptide, referred as the multiple binary complex model, seems to contribute to the amplification of immune responses and graft rejection [6,7]. The indirect pathway is related to the presentation, by host DCs, of peptides from polymorphic antigens (or neoantigens, in the case of tumors) of the donor [2]. This pathway is associated with late chronic rejection of the transplanted tissues, and it is believed that the T cells clones reactive to this polymorphic alloantigens are distinct from those activated by the direct pathway [2]. The semi-direct pathway is related to the shedding by exosomes, from donor cells, of peptide-loaded MHC into the membrane of recipient DCs, which will present donor MHC-allopeptides to T cells. Several murine studies demonstrated the acquisition of intact alloantigens to recipient DCs after vascularized allograft challenge [8–10]. The semi-direct anddirect pathway would lead to activation of the same T cell clones [2].
Ureteral anastomosis with a polyimide stent in rat kidney transplantation
Published in Renal Failure, 2020
Tong Wang, Zhou Yu, Chen Chen, Yajuan Song, Xianhui Zeng, Yingjun Su, Chenggang Yi
In the present study, we used a stent made from polyimide for ureteral anastomosis in a rat model of kidney transplantation. The findings are promising, as the stent was well tolerated and the recipients survived till the end of the experimental period. Histopathological analysis of the reconstructed ureteral segments revealed complete submucosa and lamina muscularis, although a few inflammatory cells were observed. Nonetheless, the histological structure was consistent with that of the normal ureter. But differences were found in the kidney weight among groups. At postoperative week 4 and 8, the kidney weight of the rats in group III was higher than that in the other two groups. Nevertheless, at postoperative week 12, no significant difference in kidney weight was found. And the histological changes in group III were limited. In addition, the blood creatinine level of the rats in group III was higher than that in groups I and II at postoperative week 4, 8, and 12, but no significant differences were found between groups I and II, indicating that the stent insertion would not lead to the rise of blood creatinine level. Hence the differences in kidney weights may attribute to the chronic rejection. In a word, the recovery of renal structure and function is acceptable. Thus, based on these findings, the use of this stent in ureteral reconstruction should be explored further in other animal models as well as in the clinical setting.
Ameliorative effects of curcumin towards cyclosporine-induced genotoxic potential: an in vitro and in silico study
Published in Drug and Chemical Toxicology, 2018
Ankita J. Shah, Sivakumar Prasanth Kumar, Mandava V. Rao, Himanshu A. Pandya
We conclude that the increased exposure of cells to cyclosporine leads to DNA damage and curcumin had the potential mitigating effect on cyclosporine exerted genotoxicity in vitro. Because immuosuppression in transplant recipients is required for the long term, the tumor risk of these patients increases upon prolonged administration of the immunosuppressive agent. This should be taken into consideration in transplant rejection therapy. We also presented the plausible mechanism of curcumin mitigation ability towards cyclosporine-induced genotoxic potential damaging chromosomal DNA. Using advanced in silico tools, we explained the probable mode of action of curcumin to exert its ameliorative role. We anticipate that the possible mechanism to alleviate cyclosporine-based genotoxicity by curcumin is to indirectly induce the expression of various antioxidant enzymes. We also believe that curcumin may participate in Nrf2-Keap1 pathway to upregulate the expression of detoxifying enzymes to eradicate radicals from the cellular machinery and gradually mitigates chromosomal genotoxicity which requires further molecular level elucidation.
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