Subcutaneous tissue is a promising site for islet transplantation, but poor engraftment, due to hypoxia and low vascularity, hinders its prevalence. However, oxygen partial pressure (pO2) of the subcutaneous space (SC) and other sites were reported to be equivalent in several previous reports. This contradiction may be based on accidental puncture to the indwelling micro-vessels in target tissues. We therefore developed a novel optical sensor system, instead of a conventional Clark-type needle probe, for measuring tissue pO2 and found that pO2 of the SC was extremely low in comparison to other sites. To verify the utility of this method, we transplanted syngeneic rat islets subcutaneously into diabetic recipients under several oxygenation conditions using an oxygen delivery device, then performed pO2 measurement, glucose tolerance, and immunohistochemistry. The optical sensor system was validated by correlating the pO2 values with the transplanted islet function. Interestingly, this novel technique revealed that islet viability estimated by ATP/DNA assay reduced to less than 75% by hypoxic condition at the SC, indicating that islet engraftment may substantially improve if the pO2 levels reach those of the renal subcapsular space. Further refinements for a hypoxic condition using the present technique may contribute to improving the efficiency of subcutaneous islet transplantation.
Subcutaneous islet transplantation is a promising treatment for severe diabetes; however, poor engraftment hinders its prevalence. We previously revealed that a gelatin hydrogel nonwoven fabric (GHNF) markedly improved subcutaneous islet engraftment in comparison with intraportal islet transplantation. We herein investigated whether the duration of pretreatment using GHNF affected the outcome of subcutaneous islet transplantation. A silicone spacer with GHNF was implanted into the subcutaneous space of healthy mice at 2, 4, 6, or 8 weeks before transplantation, and then diabetes was induced 7 days before transplantation. Syngeneic islets were transplanted into the pretreated space. Blood glucose, intraperitoneal glucose tolerance, immunohistochemistry, inflammatory mediators, and gene expression were evaluated. The 6-week group showed significantly better blood glucose changes than the other groups ( P < 0.05). The cure rate of the 6-week group (60.0%) was the highest among the groups (2-week = 0%, 4-week = 50.0%, 8-week = 15.4%). The number of von Willebrand factor (vWF)–positive vessels in the 6-week group was significantly higher than in the other groups at pre-islet and post-islet transplantation ( P < 0.01 [vs 2-and 4-week groups] and P < 0.05 [vs all other groups], respectively). Notably, this beneficial effect was also observed when GHNF was implanted into diabetic mice injected with streptozotocin 7 days before GHNF implantation. The positive rates for laminin, collagen III, and collagen IV increased as the duration of pretreatment became longer and were significantly higher in the 8-week group ( P < 0.01). Inflammatory mediators, including interleukin (IL)-1b, granulocyte colony-stimulating factor (G-CSF), and interferon (IFN)-γ, were gradually downregulated according to the duration of GHNF pretreatment and re-elevated in the 8-week group. Taken together, the duration of GHNF pretreatment apparently had an impact on the outcomes of subcutaneous islet transplantation, and 6 weeks appeared to be the ideal duration. Islet graft revascularization, extracellular matrix compensation of the islet capsule, and the inflammatory status at the subcutaneous space would be crucial factors for successful subcutaneous islet transplantation.
Bottle choice tests in rats are useful for the study of fat appetite. However, little is known about the feeding behavior of rats toward oxidized oil. In this study, 24-h two-bottle choice tests were performed in male Sprague-Dawley (SD) rats for 5 days. When rats were given a choice between thermally oxidized oil and fresh oil, they ingested more fresh oil. A choice test between vapor-added fresh oil and fresh oil showed that rancid flavor is involved in the avoidance of oxidized oil. Results with deodorized oxidized oil indicated that a nonvolatile product also influenced choice. In conclusion, rats could distinguish oxidized oil from fresh oil and preferred fresh oil.
Background Undifferentiated embryonal sarcoma of the liver (UESL) primarily occurs in children; it is rarely seen in adults and appears to have a poor prognosis. However, in recent years, some cases indicated that long-term survival was possible due to a combination of multiple surgeries, chemotherapy, and liver transplantation. Case presentation A 33-year-old female patient presented with a complaint of epigastric pain, for which she underwent a medical examination. Computed tomography (CT) and magnetic resonance imaging showed a cystic tumor in the right hepatic lobe, approximately 10 cm in size. During observation, the abdominal pain worsened, and a contrast-enhanced CT revealed that the tumor’s peripheral solid components increased in size and volume, suggesting a malignant tumor threatening hepatic rupture. Subsequently, transcatheter arterial embolization of the anterior and posterior segmental branches of the hepatic artery was performed, followed by right trisectionectomy. Histopathological and immunohistochemical examinations of the lesion revealed UESL. Two months after the surgery, we initiated sarcoma-directed chemotherapy with doxorubicin because of multiple metastases to the liver. After initiating the chemotherapy, she received another regimen using gemcitabine/docetaxel, eribulin, trabectedin, ifosfamide/mesna, pazopanib, and cisplatin. During the chemotherapy, she underwent palliative surgery twice due to the progressive disease. She lived for 49 months after the initial operation. Conclusions Improved long-term survival was achieved in an adult patient with UESL after multidisciplinary therapy, involving a combination of three surgical procedures and several chemotherapies.
In patients with type 1 diabetes mellitus and end-stage renal failure, kidney and pancreas transplantation is the best therapeutic option. Target: To present the clinical results in patients with type 1 diabetes mellitus and end-stage renal failure who underwent simultaneous kidney and pancreas transplantation. Materials and methods: Since 2009, 10 kidney and pancreas transplants have been performed at the Almenara hospital, including 10 patients who underwent simultaneous kidney and pancreas transplantation. Nonparametric statistical analysis was performed and survival was estimated using the Kaplan-Meier method. Results: Between 2009 and 2021, 10 simultaneous kidney and pancreas transplants were performed. The male gender 60%, with an age -at the time of transplantation -of 31 years, and a time elapsed from the start of dialysis support to transplantation of 61 months 70% of the population had dialysis support by hemodialysis 20% peritoneal dialysis and 10% pre-dialysis, Average age of cadaveric donor 25 years, glycemic control was achieved between 24 and 48 hours after surgery. 20% presented delayed function of the renal graft, of this group 50% ended up in graftectomy due to anatomopathological finding, post-reperfusion syndrome associated with thrombosis, survival was 100% per year, and that of the pancreatic graft, 90% per year, values comparable to the best expected results. Conclusion: Simultaneous kidney and pancreas transplantation is the best surgical option for controlling complications secondary to type 1 diabetes mellitus and end-stage renal failure. The small number of the sample reflects the lack of donors, a situation that worsened with the COVID pandemic.
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