The ischemia-reperfusion injury (IRI) remains a major problem in transplantation. The objective of this study was to evaluate the effects of preconditioning a donor group with rapamycin and another donor group with tacrolimus to prevent IRI. Twelve hours before nephrectomy, donor Wistar rats received immunosuppressive drugs. The sample was divided into four experimental groups: a sham group, an untreated control group, a group treated with rapamycin (2 mg/kg) and a group treated with tacrolimus (0.3 mg/kg). Left kidneys were removed and, after three hours of cold ischemia, grafts were transplanted. Twenty-four hours later, the transplanted organs were recovered for histological analysis and evaluation of cytokine expression. The pre-conditioning treatment with rapamycin or tacrolimus significantly reduced donor blood urea nitrogen and creatinine levels compared with control group (BUN: p < 0.001 vs. control and creatinine: p < 0.001 vs. control). Acute tubular necrosis was significantly lower in donors treated with immunosuppressant drugs compared with the control group (p < 0.001). Finally, inflammatory cytokines such as TNF-a, IL-6 and rIL-21 showed lower levels in the graft of pre-treated animals. This exploratory experimental study shows that preconditioning donors with rapamycin and tacrolimus in different groups improves clinical outcome and pathology in recipients and reduces in situ pro-inflammatory cytokines associated with Th17 differentiation, creating a favorable environment for the differentiation of regulatory T cells (Tregs).
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J Pharm Biomed Anal
December 2024
Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, the Netherlands; Leiden Network for Personalized Medicine, Leiden, the Netherlands. Electronic address:
Voclosporin is a potent immunosuppressive agent currently approved for treating active lupus nephritis. Based on its potential antiviral activity, it has also been investigated as immunosuppressive agent in an investigator-initiated study in SARS-CoV2 positive kidney transplant recipients. As with many immunosuppressive agents, optimizing dosing regimens to achieve therapeutic efficacy while minimizing toxicity remains a critical challenge in clinical practice.
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December 2024
Department of Kidney and Transplant Services, Princess Alexandra Hospital, Brisbane, Australia.
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View Article and Find Full Text PDFGenes Cells
January 2025
Laboratory of Molecular Pharmacogenomics, Department of Pharmaceutical Sciences, Kindai University, Higashiosaka, Japan.
Aggregation of alpha-synuclein (α-Syn) is implicated in the pathogenesis of several neurodegenerative disorders, such as Parkinson's disease and Dementia with Lewy bodies, collectively termed synucleinopathies. Thus, tremendous efforts are being made to develop strategies to prevent or inhibit α-Syn aggregation. Here, we genetically engineered fission yeast to express human α-Syn C-terminally fused to green fluorescent protein (GFP) at low and high levels.
View Article and Find Full Text PDFClin Transplant
December 2024
Department of Surgery, IU Health/Indiana University School of Medicine, Indianapolis, Indiana, USA.
This single-center retrospective study was designed to evaluate the use of basiliximab as an alternative rescue maintenance immunosuppression in situations where standard maintenance immunosuppression is not tolerated after a pancreas transplant. All pancreas transplants performed between January 11, 2006, and January 6, 2022, were reviewed. All recipients received rabbit antithymocyte globulin (rATG) induction with tacrolimus + sirolimus maintenance for simultaneous pancreas and kidney (SPK) and additional low-dose mycophenolic acid for pancreas transplant alone (PTA).
View Article and Find Full Text PDFElife
December 2024
Institute of Biochemistry, University of Kiel, Kiel, Germany.
The development of proteolysis targeting chimeras (PROTACs), which induce the degradation of target proteins by bringing them into proximity with cellular E3 ubiquitin ligases, has revolutionized drug development. While the human genome encodes more than 600 different E3 ligases, current PROTACs use only a handful of them, drastically limiting their full potential. Furthermore, many PROTAC development campaigns fail because the selected E3 ligase candidates are unable to induce degradation of the particular target of interest.
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