Elevated Expression of Pyrimidine Nucleoside Phosphorylase (PyNPase) in Renal Cell Carcinoma Tissue

Background: Pyrimidine nucleoside phosphorylase (PyNPase) is an enzyme that converts 5\u27-deoxy-5-fluorouridine to 5- fluorouracil. PyNPase is identical to platelet-derived endothelial cell growth factor (PD-ECGF), and has angiogenic activity. In the present study of PyNPase activity in renal cell carcinoma, we tested for correlation between PyNPase activity and tumor extension, tumor proliferation and clinical characteristics. Methods: Samples of tumor tissue and non-tumor tissue were obtained from 10 renal cell carcinoma patients who underwent radical nephrectomy. These samples were examined, and PyNPase activity of the tissues was assayed. Results: PyNPase activity was significantly higher in renal cancer tissue than in normal tissue (p<0.01), and in immunohistochemical assays PyNPase was strongly stained in the cytoplasm of renal cancer cells. However, there were no significant correlation between PyNPase activity and tumor extension, according to the results of histopathological examination and evaluation of vascularity of renal cancer tumor tissue. Conclusion: In this study, we did not observe correlation between PyNPase activity and renal cancer extension and proliferation. However, the present data suggest that pyrimidine-class drugs may be useful against renal cell carcinoma, because PyNPase activity is significantly higher in renal cancer tissue than in normal tissue

Effect of oral intake of royal jelly on endothelium function in hemodialysis patients: study protocol for multicenter, double-blind, randomized control trial

Background: Hemodialysis (HD) is a common renal replacement therapy for patients with renal failure. Cardiovascular and cerebrovascular diseases are known to shorten survival periods and worsen the quality of life of HD patients. Atherosclerosis is a major cause of vascular diseases, and various factors such as abnormality of lipid metabolism and increased macrophage activity, oxidative stress, and endothelial dysfunction are associated with its pathogenesis and progression. Further, endothelial stem cells (ESCs) have been reported to play important roles in endothelial functions. Royal jelly (RJ) affects atherosclerosis- and endothelial function-related factors. The main aim of this trial is to investigate whether oral intake of RJ can maintain endothelial function in HD patients. In addition, the effects of RJ intake on atherosclerosis, ESC count, inflammation, and oxidative stress will be analyzed.Methods: This will be a multicenter, prospective, double-blind, randomized controlled trial. We will enroll 270 participants at Nagasaki Jin Hospital, Shinzato Clinic Urakami, and Maeda Clinic, Japan. The participants will be randomized into RJ and placebo groups. The trial will be conducted according to the principles of the Declaration of Helsinki, and all participants will be required to provide written informed consent. The RJ group will be treated with 3600 mg/day of RJ for 24 months, and the placebo group will be treated with starch for 24 months. The primary endpoint will be the change in flow-mediated dilation (FMD), a parameter of endothelium function, from the time before treatment initiation to 24 months after treatment initiation. The secondary and other endpoints will be changes in FMD; ESC count; serum levels of vascular endothelial cell growth factor, macrophage colony-stimulating factor, 8-hydroxydeoxyguanosine, and malondialdehyde; the incidence of cardiovascular diseases, cerebrovascular diseases, and stenosis of blood access; and safety.Discussion: This trial will clarify whether oral intake of RJ can maintain endothelial function and suppress the progression of atherosclerosis in HD patients. In addition, it will clarify the effects of RJ on ESCs, oxidative stress, and angiogenic activity in blood samples.Trial registration: The Japan Registry of Clinical Trials jRCTs071200031. Registered on 7 December 2020

表在性膀胱腫瘍におけるAngiogeninの発現

20名の表在性膀胱腫瘍患者の腫瘍組織内と正常組織内各々のangiogenin濃度をサンドウィッチELISA法を用い測定し, 膀胱組織内におけるangiogeninの局在を明らかにする目的で免疫染色を行った.腫瘍組織内のangiogenin濃度は正常組織内の濃度と比較して有意に低下し, angiogeninの発現は正常移行上皮に高く, 腫瘍組織内で明らかに低下していた.膀胱腫瘍患者の組織内でのangiogeninの発現は正常組織と比較すると腫瘍組織内で有意に低下していた.この結果は, 膀胱腫瘍の発育の過程ではangiogeninは他の血管新生因子とは異なる役割を担っている可能性が示唆されたThe concentration of angiogenin in the tumor tissues and corresponding normal tissues of 20 superficial bladder cancer patients was measured using a sandwich enzyme immunoassay (ELISA). In addition, immunohistochemical assays were performed in order to clarify the localization of angiogenin expression in bladder tissue. The mean concentration of angiogenin in the carcinoma tissues was significantly lower than that in the corresponding normal tissues (P < 0.001). Angiogenin expression was weak in the bladder cancer cells. The present results show that the expression of angiogenin is lower in superficial bladder cancer tissues than in corresponding normal tissues. The biological role of angiogenin in carcinogenesis of bladder cancer may be different from those of other angiogenic factors

Effect of oral intake of royal jelly on endothelium function in hemodialysis patients: study protocol for multicenter, double-blind, randomized control trial

BACKGROUND: Hemodialysis (HD) is a common renal replacement therapy for patients with renal failure. Cardiovascular and cerebrovascular diseases are known to shorten survival periods and worsen the quality of life of HD patients. Atherosclerosis is a major cause of vascular diseases, and various factors such as abnormality of lipid metabolism and increased macrophage activity, oxidative stress, and endothelial dysfunction are associated with its pathogenesis and progression. Further, endothelial stem cells (ESCs) have been reported to play important roles in endothelial functions. Royal jelly (RJ) affects atherosclerosis- and endothelial function-related factors. The main aim of this trial is to investigate whether oral intake of RJ can maintain endothelial function in HD patients. In addition, the effects of RJ intake on atherosclerosis, ESC count, inflammation, and oxidative stress will be analyzed. METHODS: This will be a multicenter, prospective, double-blind, randomized controlled trial. We will enroll 270 participants at Nagasaki Jin Hospital, Shinzato Clinic Urakami, and Maeda Clinic, Japan. The participants will be randomized into RJ and placebo groups. The trial will be conducted according to the principles of the Declaration of Helsinki, and all participants will be required to provide written informed consent. The RJ group will be treated with 3600 mg/day of RJ for 24 months, and the placebo group will be treated with starch for 24 months. The primary endpoint will be the change in flow-mediated dilation (FMD), a parameter of endothelium function, from the time before treatment initiation to 24 months after treatment initiation. The secondary and other endpoints will be changes in FMD; ESC count; serum levels of vascular endothelial cell growth factor, macrophage colony-stimulating factor, 8-hydroxydeoxyguanosine, and malondialdehyde; the incidence of cardiovascular diseases, cerebrovascular diseases, and stenosis of blood access; and safety. DISCUSSION: This trial will clarify whether oral intake of RJ can maintain endothelial function and suppress the progression of atherosclerosis in HD patients. In addition, it will clarify the effects of RJ on ESCs, oxidative stress, and angiogenic activity in blood samples. TRIAL REGISTRATION: The Japan Registry of Clinical Trials jRCTs071200031.  Registered on 7 December 2020

Bartter syndrome representing digenic-based salt-losing tubulopathies presumably accelerated by renal insufficiency

Bartter syndrome and Gitelman syndrome (GS) are autosomal recessive disorders usually caused by homozygous or compound heterozygous mutations in causative genes. In some patients, these two syndromes cannot be discriminated based on clinical features or mutation type; thus, a single disease concept, salt-losing tubulopathies (SLTs), has been used instead. Despite the existence of several SLT causative genes, cases of digenic heterozygous mutations in two different genes are extremely rare. Here, we report the case of a 36-year-old woman with renal insufficiency and hypokalemia caused by an SLT. To evaluate the SLT phenotype, we performed next-generation sequencing (NGS) with a gene panel including SLC12A3,SLC12A1, CLCNKB, and CLCNKA as well as laboratory examinations and diuretic loading tests. The results of the diuretic loading tests were consistent with a GS phenotype, while the NGS results showed that the patient had heterozygous mutations in SLC12A1 and CLCNKB. Both genes have been associated with BS,suggesting that the SLT was caused by digenic heterozygous mutations in two different genes. To date, only a few SLT cases caused by digenic heterozygous mutations in two different genes have been reported. The digenic SLT phenotype in the patient was presumably accelerated by moderate renal insufficiency