Uterus transplantation (UTx) is the first and only available treatment for women with absolute uterine factor infertility. However, clinical application is limited by the lack of organs, ischemia/reperfusion injury, as well as immunosuppression after UTx. Several different preservation solutions are used in experimental and clinical UTx, including Custodiol® solution. Recently, the novel Custodiol-N solution was developed with superior results in organ preservation. However, the solution was not tested yet in UTx. Therefore, the aims of this study were to evaluate the effect of Custodiol-N in uterus prolonged cold preservation time (8 and 24 h), compared to Custodiol® solution. Uterus tissue samples were obtained from adult Sprague Dawley rats (n = 10/group). Cold ischemic injury was estimated by histology, including immunohistochemistry, and biochemical tissue analyses. After 8 h of cold ischemia, higher percentage of tissue edema, necrosis signs and myeloperoxidase expression, as well as lower superoxide dismutase activity were found in Custodiol® compared to Custodiol-N (p < 0.05). These differences were more pronounced after 24 h of cold preservation time (p < 0.05). This study demonstrated that Custodiol-N protects uterus grafts from cold ischemic injury better than standard Custodiol® most likely via inhibition of oxidative stress and tissue edema. It seems that iron chelators in the composition of Custodiol-N play an important protective role against cold ischemia.
Ischemia/reperfusion injury (IRI) remains a significant problem to be solved in uterus transplantation (UTx). Melatonin and glycine have been shown to possess direct cytoprotective activities, mainly due to their antioxidative and anti-inflammatory properties. The aim of this study was to investigate the protective effects of melatonin and glycine and their combination on IRI in a rat model of warm ischemia. In this study, Sprague-Dawley rats were assigned to eight groups, including sham and IRI (n = 80). Melatonin and glycine alone or their combination were administered prior to 1 h of uterus ischemia followed by 1 h of reperfusion. Melatonin (50 mg/kg) was administered via gavage 2 h before IRI and glycine in an enriched diet for 5 days prior to intervention. Uterus IRI was estimated by histology, including immunohistochemistry, and biochemical tissue analyses. Histology revealed that uterus IRI was significantly attenuated by pretreatment with melatonin (p = 0.019) and glycine (p = 0.044) alone as well as their combination (p = 0.003). Uterus IRI led to increased myeloperoxidase expression, which was significantly reduced by melatonin (p = 0.004), glycine (p < 0.001) or their combination (p < 0.001). The decline in superoxide dismutase activity was significantly reduced in the melatonin (p = 0.027), glycine (p = 0.038) and combined treatment groups (p = 0.015) when compared to the IRI control group. In conclusion, melatonin, glycine and their combination significantly reduced oxidative stress-induced cell damage after IRI in a small animal warm ischemia model, and, therefore, clinical studies are required to evaluate the protective effects of these well-characterized substances in uterus IRI.
Perivascular epithelioid cell tumor (PEComa) is a rare entity, characterized as a mesenchymal tumor with coexpression of melanocytic and smooth muscle markers. The involvement of the gastrointestinal tract is described in up to 100 cases in the English literature. Rectal PEComas are even more uncommon, with only 10 previously described cases. We present the case of a 62-year-old man with rectal PEComa with some unusual features, such as gastrointestinal stromal tumor–like CD117 positivity and HMB45 (human melanoma black-45)–positive multinucleated giant tumor cells. After 12 months' follow-up, the patient is alive with no radiologic, endoscopic, or histologic evidence of disease recurrence.
Paragangliomas of the head and neck are uncommon tumors arising from parasympathetic ganglia. Paragangliomas are mostly asymptomatic and may manifest as palpable mass of neck. The morphologic features are non-specific and comparable to the other neuroendocrine tumors. Most of hereditary cases are associated with alterations in genes of succinate dehydrogenase (SDH). SDHA and SDHB immunohistochemistry is considered as reliable screening method to detect tumors with genetical alterations. Of note, SDHB mutated paragangliomas have the highest risk of local recurrence, distant metastasis and the development of other tumor phenotypes, which are associated with mutation. Therefore, active surveillance of patients and early surgical treatment are essential. In contrast, SDHB mutated head and neck paragangliomas was considered as completely benign tumors, although, the latest literature describes more controversial cases, which may increase awareness. Here, we present a rare case of 21 years old female with asymptomatic neck paraganglioma, which was unexpectedly diagnosed after pathological and immunohistochemical testing of removed thyroid gland and showed unusual immunohistochemical variation for SDH mutation.
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