Abstract Das bicyclische Carbinol (I) reagiert mit Fluorsulfonsäure/SOQ über kationische Zwischenstufen wie (II) zum Carbinol (III), das zum Keton (IV) oxidiert werden kann.
Background/aims. We have reported that tubular epithelial cell injury caused by renal ischemia−reperfusion is attenuated in conditional VHL knockout (VHL-KO) mice and also that induction of hypoxia-inducible factor (HIF) suppresses angiotensin II-accelerated Habu snake venom (HV) glomerulonephropathy in rats. However, it remains unknown whether VHL knockdown protects glomerular endothelial cells from endothelium-targeted glomerulonephritis. Methods and results.VHL-KO mice with HV glomerulonephropathy (HV GN) had fewer injured glomeruli, a lower mesangiolysis score and reduced blood urea nitrogen levels. Immunoreactivity of vascular endothelial growth factor (VEGF) in the glomerular capillaries was enhanced by VHL knockdown and was conserved even in VHL-KO mice with HV GN, despite HV-attenuating endothelial VEGF expression in vitro . VHL-KO mice showed enhanced nitric oxide (NO) production in glomerular endothelial cells and tubular cells, associated with activated VEGF expression in the kidney (i.e. an activated NO–VEGF axis). The levels of NO in glomeruli and tubules were conserved even in mice with HV GN. In contrast, suppressing NO production in glomerular endothelial cells by an NO synthase inhibitor, Nϖ -nitro- L -arginase, completely blunted the protection of VHL-KO from HV GN. The activated NO-VEGF axis in the kidney of VHL-KO mice was also associated with an elevation in Flk-1 phosphorylation and increased levels of IL-10 and IP-10. Conclusion. Conditional VHL knockdown may enhance the NO–VEGF axis and protect glomerular endothelial cells from HV GN, thereby providing resistance to injury of tubular epithelial cells and glomerular endothelial cells.
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Abstract: We investigated the biological activity of W9, a bone resorption inhibitor peptide, using NanoClik nanoparticles as an injectable carrier, where acryloyl group-modified cholesterol-bearing pullulan (CHPOA) nanogels were crosslinked by pentaerythritol tetra (mercaptoethyl) polyoxyethylene. Thirty 5-week-old male C57BL/6J mice were fed a low calcium diet and received once-daily subcutaneous injections of the carrier alone, W9 24 mg/kg/day alone, W9 24 mg/kg/day incorporated in cholesterol bearing pullulan (CHP) nanogels, or W9 (8 and 24 mg/kg/day) incorporated in NanoClik nanoparticles for 4 days (n=5). Mice that received a normal calcium diet with NanoClik nanoparticle injections without W9 were used as a control group. Radiological analyses showed that administration of W9 24 mg/kg/day significantly prevented low calcium-induced reduction of bone mineral density in the long bones and lumbar vertebrae, but only when the NanoClik nanoparticles were used as a carrier. Histomorphometric analyses of the proximal tibiae revealed that W9 24 mg/kg/day incorporated in NanoClik nanoparticles prevented the increase in bone resorption indices induced by a low calcium diet, which was confirmed by measurement of serum bone resorption markers. These data suggest that NanoClik nanoparticles could be a useful carrier for peptide therapeutics, and also demonstrate that daily subcutaneous injections of the W9 peptide with the nanoparticles were able to inhibit bone loss in vivo. An osteoclastogenesis inhibition assay performed in vitro confirmed a slower release profile of W9 from NanoClik nanoparticles compared with conventional CHP nanogels. Keywords: nanocarrier, peptide drug, injectable drug carrier, polyethylene glycol crosslinking, cholesterol-bearing pullulan, controlled release
As elderly society progresses, development of welfare equipment for assisting human to motion is getting more important nowadays. We develop welfare equipment to assist motion and evaluate the effect of this machine on the muscle tension of the user. Our evaluation method will be useful for developing a machine for practical purposes.
he patient was a 32-year-old woman, who complained the facial weakness and the tinnitus on the right side, and occasionally the headaches, of two years'duration.The right external auditory canal was filled with the grayish-pink tumor that had cartilage-like consistency and smooth surface. Another local findings were almost normal without the palsy of the right-sided 7th nerve. The hearing tests revealed the pure conductive deafness on the right ear. The vestibular function was normal. X-ray findings showed a small destructive process on the right petrous bone. Pre- operatively, a biopsy of the graunlar mass in the right external auditory meatus confirmed the original diagnosis of the glomus jugular tumor.The postaural radical mastoidectomy was performed without excessive bleeding under local anesthesia. The main tumor filled the entire external auditory canal, and invaded the lower part of the petrous bone and the base of the external in size of the little finger.After operation, deep X-ray therapy (2400r.) and implanatation of radon seeds (5mc) were applied. There has been no recurrence observed for two years. This case is apparently the third report of the glomus jugulare tumor from Japan.
We experienced a case of primary malignant lymphoma of the spleen which presented difficulty in diagnosis before and during operation. A 68-year-old man was accidentally diagnosed as having tumors in the hilum of the spleen by an abdominal CT conducted during a follow-up survey for cholelithiasis. As ultrasonography, EUS, abdominal MRI, angiography and other examinations failed to offer the definite diagnosis, laparotomy was carried out. Enucleation of the tumors was attemptd at first, but hemorrhage occurred and so a splenectomy inculding the tumors in the splenic hilum was performed. After the operation a tumor measuring 1.2cm in diameter in the cut surface of the resected spleen was found for the first time. Eventually, the resected splenic tumor was diagnosed s malignant lymphoma of diffuse small or medium-sized cell type (B cell type) with metastasis to regional lymphnodes by histopathologic examination. The solitary primary splenic lesion in this case was the smallest one among those reported thus far in Japan to the authors' best knowledge.
