Cisplatin, rather than oxaliplatin, increases paracellular permeability of LLC-PK1 cells via activating protein kinase C

The clinical use of cisplatin is limited by its adverse events, particularly serious nephrotoxicity. It was clarified that cisplatin is transported by a kidney-specific organic cation transporter (OCT2). OCT2 also mediates the uptake of oxaliplatin into renal proximal tubular cells; however, this agent does not lead nephrotoxicity. In the present study, we carried out comparative experiments with cisplatin and oxaliplatin using porcine kidney LLC-PK1 cell monolayers. In the fluorescein-labeled isothiocyanate-dextran flux assay, the basolateral application of cisplatin, but not oxaliplatin, resulted in an increase in the paracellular permeability of cell monolayers. Even though the cellular accumulation of platinum at 50 μM oxaliplatin could reach the same level at 30 μM cisplatin, oxaliplatin did not induce hyper-permeability in cell monolayers. Cisplatin, but not oxaliplatin, significantly activated PKC. In addition, the combination of PKC inhibitors recovered the increase in paracellular permeability. In conclusion, pharmacodynamic mechanisms via PKC could explain the difference in nephrotoxicity between cisplatin and oxaliplatin

携帯端末向けセンサ統合型省電力ジオフェンシングの研究

学位の種別: 課程博士審査委員会委員 : （主査）東京大学教授 森川 博之, 東京大学教授 西成 活裕, 東京大学教授 瀬崎 薫, 東京大学准教授 矢入 健久, 東京大学准教授 豊田 正史University of Tokyo(東京大学

Synthesis of solvent-free conductive and flexible cellulose-carbon nanohorn sheets and their application as a water vapor sensor

Carbon nanohorns (CNHs) are mixed with cellulose to make freestanding thin-film conductive sheets. CNHs, at different ratios (5, 10, 25, 50 wt%), form composites with cellulose (hydroxyethylcellulose). Freestanding cellulose-carbon nanohorn (CCN) sheets were fabricated using a 100 mu m-thick metal bar coater. Surfactants or any other chemical treatments to tailor the surface properties of CNHs were avoided to obtain composite sheets from pristine CNHs and cellulose. Utilizing the hygroscopic property of hydroxyethylcellulose and the electrical conductivity of CNHs paved a path to perform this experiment. The synthesis technique is simple, and the fabrication and drying of the sheets were effortless. As the loading concentration of CNH increased, the resistance, flexibility, and strength of the CCN composite sheets decreased. The maximum loading concentration possible to obtain a freestanding CCN sheet is 50 wt%. The resistance of the maximum loading concentration of CNH was 53 k omega. The response of the CCN sheets to water vapor was 4 s and recover time was 13 s, and it is feasible to obtain a response for different concentrations of water vapor. High-resolution transmission electron microscopy, scanning electron microscopy, Fourier transform infrared spectroscopy, Raman spectroscopy, resistance measurement, tensile strength measurement, and thermogravimetric analysis were used to investigate the mechanical, morphological, electrical, and chemical properties of the CCN sheets

Effect of riboflavin deficiency on development of the cerebral cortex in Slc52a3 knockout mice

Riboflavin transporter 3 (RFVT3), encoded by the SLC52A3 gene, is important for riboflavin homeostasis in the small intestine, kidney, and placenta. Our previous study demonstrated that Slc52a3 knockout (Slc52a3−/−) mice exhibited neonatal lethality and metabolic disorder due to riboflavin deficiency. Here, we investigated the influence of Slc52a3 gene disruption on brain development using Slc52a3−/− embryos. Slc52a3−/− mice at postnatal day 0 showed hypoplasia of the brain and reduced thickness of cortical layers. At embryonic day 13.5, the formation of Tuj1+ neurons and Tbr2+ intermediate neural progenitors was significantly decreased; no significant difference was observed in the total number and proliferative rate of Pax6+ radial glia. Importantly, the hypoplastic phenotype was rescued upon riboflavin supplementation. Thus, it can be concluded that RFVT3 contributes to riboflavin homeostasis in embryos and that riboflavin itself is required during embryonic development of the cerebral cortex in mice

Lactobacillus helveticus SBT2171 Attenuates Experimental Autoimmune Encephalomyelitis in Mice

We recently reported that Lactobacillus helveticus SBT2171 (LH2171) inhibited the proliferation and inflammatory cytokine production of primary immune cells in vitro, and alleviated collagen-induced arthritis (CIA) in mice, a model of human rheumatoid arthritis (RA). In this study, we newly investigated whether LH2171 could relieve the severity of experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS), which is an autoimmune disease, but develop the symptoms by different mechanisms from RA. In MS and EAE, main cause of the disease is the abnormality in CD4+ T cell immunity, whereas in RA and CIA, is that in antibody-mediated immunity. The intraperitoneal administration of LH2171 significantly decreased the incidence and clinical score of EAE in mice. LH2171 also reduced the numbers of pathogenic immune cells, especially Th17 cells, in the spinal cord at the peak stage of disease severity. Interestingly, before the onset of EAE, LH2171 administration remarkably decreased the ratio of Th17 cells to CD4+ T cells in the inguinal lymph nodes (LNs), where pathogenic immune cells are activated to infiltrate the central nervous system, including the spinal cord. Furthermore, the expression of interleukin (IL)-6, an inflammatory cytokine essential for Th17 differentiation, decreased in the LNs of LH2171-administered mice. Moreover, LH2171 significantly inhibited IL-6 production in vitro from both DC2.4 and RAW264.7 cells, model cell lines of antigen-presenting cells. These findings suggest that LH2171 might down-regulate IL-6 production and the subsequent Th17 differentiation and spinal cord infiltration, consequently alleviating EAE symptoms