Objective: The aim of the present study was to validate an experimental model of heterotopic renal allotransplantation. Such a model, more relevant to the human situation, has never been previously described.
Materials And Methods: Pietrin pigs (40 to 50 kg) were used in the study. Through a midline incision, the left kidney was removed, washed, and preserved in a standard preservation solution (Celsior, Genzyme, France) for 20 hours at 4 °C. Heterotopic autotransplantation was performed into the right iliac fossa onto the external iliac vessels with an end-to-side anastomosis and a nonstented uretero-ureteral anastomosis was performed.
Results: Twenty-five renal allotransplantations were performed over a 5-month time period. Mean operating time progressively decreased and stabilized after 15 procedures (mean ± SD: 78.2 ± 19 minutes and 187.4 ± 18 minutes for left nephrectomy and transplantation, respectively) as morbidity decreased concomitantly. Suturing times for end-to-side anastomosis of the renal artery and vein onto the external iliac artery and vein were 21.9 ± 7 minutes and 34 ± 8 minutes (mean ± SD), respectively. Ten pigs died before the end of the experiment.
Conclusions: We have developed and validated the first nonrodent animal model of heterotopic renal autotransplantation relevant to the human anatomy and physiology. The procedure was easy to learn and safe. This model could be used to teach junior surgeons renal transplantation techniques and could also be used as a model to study ischemia-reperfusion injury in renal transplantation.
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http://dx.doi.org/10.1016/j.transproceed.2012.03.055 | DOI Listing |
Int J Mol Sci
January 2025
Instituto de Investigação e Inovação em Saúde da Universidade do Porto-i3S, R. Alfredo Allen 208, 4200-135 Porto, Portugal.
Diffuse noxious inhibitory control (DNIC), also known as conditioned pain modulation (CPM) in humans, is a paradigm wherein the heterotopic application of a noxious stimulus results in the attenuation of another spatially distant noxious input. The pre-clinical and clinical studies show the involvement of several neurochemical systems in DNIC/CPM and point to a major contribution of the noradrenergic, serotonergic, and opioidergic systems. Here, we thoroughly review the latest data on the monoaminergic and opioidergic studies, focusing particularly on pre-clinical models of chronic pain.
View Article and Find Full Text PDFDrug Deliv
December 2025
Department of Medicine, Faculty of Biomedical and Health Sciences, Universidad Europea de Madrid, Madrid, Spain.
Recent studies on head and neck squamous cell carcinoma (HNSCC) tumorigenesis have revealed several dysregulated molecular pathways. The phosphatidylinositol-3-kinase (PI3K) signaling pathway is frequently activated in HNSCC, making it an attractive target for therapies. PHT-427 is a dual inhibitor of PI3K and the mammalian target of AKT/PDK1.
View Article and Find Full Text PDFCommun Med (Lond)
January 2025
Department of Surgery, The University of Maryland School of Medicine, Baltimore, MD, USA.
Background: Improvement in gene modifications of donor pigs has led to the prevention of early cardiac xenograft rejection and significantly prolonged cardiac xenograft survival in both heterotopic and orthotopic preclinical non-human primate (NHP) models. This progress formed the basis for FDA approval for compassionate use transplants in two patients.
Methods: Based on our earlier report of 9-month survival of seven gene-edited (7-GE) hearts transplanted (life-supporting orthotopic) in baboons, we transplanted 10 gene-edited pig hearts into baboons (n = 4) using non-ischemic continuous perfusion preservation (NICP) and immunosuppression regimen based on co-stimulation blockade by anti-CD40 monoclonal antibody.
J Immunother Cancer
January 2025
Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri, USA
Background: Treatment with immunotherapy can elicit varying responses across cancer types, and the mechanistic underpinnings that contribute to response vrsus progression remain poorly understood. However, to date there are few preclinical models that accurately represent these disparate disease scenarios.
Methods: Using combinatorial radio-immunotherapy consisting of PD-1 blockade, IL2Rβγ biased signaling, and OX40 agonism we were able to generate preclinical tumor models with conflicting responses, where head and neck squamous cell carcinoma (HNSCC) models respond and pancreatic ductal adenocarcinoma (PDAC) progresses.
Adv Sci (Weinh)
December 2024
Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Institute of Pediatrics, National Children's Medical Center, Children's Hospital, Fudan University, Shanghai, 200032, China.
Focal cortical dysplasia (FCD) is a highly heterogeneous neurodevelopmental malformation, the underlying mechanisms of which remain largely elusive. In this study, personalized dorsal and ventral forebrain organoids (DFOs/VFOs) are generated derived from brain astrocytes of patients with FCD type II (FCD II). The pathological features of dysmorphic neurons, balloon cells, and astrogliosis are successfully replicated in patient-derived DFOs, but not in VFOs.
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