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Up-Regulation of Local TGF-β Contributes to a Decrease in Renal Tubular Na⁺-K⁺ ATPase and Hyperkalemia in a Mouse Model of Crush Syndrome

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Pharmacology & Pharmacy 2016年第12期7卷 481-492页

作者： Shinya Mizuno yoko Mizuno-horikawa Department of Biochemistry Osaka University Graduate School of Medicine Suita Japan Department of Immunology and Microbiology Osaka University Graduate School of Medicine Suita Japan The Institute of Experimental Animal Sciences Suita Japan

Hyperkalemia is one of the most important risk factors in patients suffering from crush syndrome with rhabdomyolysis. Glycerol-injected animals have been used as an experimental model of rhabdomyolysis-induced acute kidney injury (AKI), but little information is available for the onset and molecular mechanism of hyperkalemia. In our murine model, plasma potassium levels increased after a single injection of 50%-glycerol solution (10 ml/kg, i.m.) during the progression of muscular and renal injuries. Renal tubular Na+-K+-ATPase functions as ion-exchange pomp for potassium clearance from blood into renal tubular epithelial cells. Renal histochemistry revealed an apparent decrease in the tubular Na+-K+-ATPase expression, especially at 24 hours post-glycerol challenge in our AKI model. In contrast to the loss in active Na+-K+-ATPase, there was a significant increase in the renal levels of transforming growth factor-β (TGF-β) that is known to suppress Na+-K+-ATPase production in vitro. When anti-TGF-β antibody was administered in mice after the glycerol challenge, the suppression of renal Na+-K+-ATPase activity was partially restored. As a result, hyperkalemia was improved in the TGF-β-neutralized AKI mice, associated with a significant decrease in plasma potassium concentration. Taken together, we predict that endogenous TGF-β is a key regulator for inhibiting Na+-K+-ATPase production and, in part, enhancing hyperkalemia during progression of rhabdomyolysis-induced AKI. This is, to our knowledge, the first report to determine a critical role of endogenous TGF-β in renal potassium metabolism during crush syndrome.

关键词： Rhabdomyolysis AKI Hyperkalemia Na+-K+-ATPase TGF-β

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The Adenosine Receptor Agonist 5’-N-Ethylcarboxamide-Adenosine Increases Mouse Serum Total Homocysteine Levels, Which Is a Risk Factor for Cardiovascular Diseases

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Pharmacology & Pharmacy 2015年第10期6卷 461-470页

作者： Shigeko Fujimoto Sakata Koichi Matsuda yoko horikawa Yasuto Sasaki Faculty of Nutrition Kobe Gakuin University Kobe Japan

An increase in total homocysteine (Hcy) levels (protein-bound and free Hcy in the serum) has been identified as a risk factor for vascular diseases. Hcy is a product of the methionine cycle and is a precursor of glutathione in the transsulfuration pathway. The methionine cycle mainly occurs in the liver, with Hcy being exported out of the liver and subsequently bound to serum proteins. When the non-specific adenosine receptor agonist 5’-N-ethylcarboxamide-adenosine (NECA;0.1 or 0.3 mg/kg body weight) was intraperitoneally administered to mice that had been fasted for 16 h, total Hcy levels in the serum significantly increased 1 h after its administration. The NECA treatment may have inhibited transsulfuration because glutathione levels were significantly decreased in the liver. After the intraperitoneal administration of a high dose of NECA (0.3 mg/kg body weight), elevations in total Hcy levels in the serum continued for up to 10 h. The mRNA expression of methionine metabolic enzymes in the liver was significantly reduced 6 h after the administration of NECA. NECA-induced elevations in total serum Hcy levels may be maintained in the long term through the attenuated expression of methionine metabolic enzymes.

关键词： Adenosine 5’-N-Ethylcarboxamide-Adenosine Glutathione Homocysteine

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The Adenosine Receptor Agonist 5’-N-Ethylcarboxamide-Adenosine Increases Glucose 6-Phosphatase Expression and Gluconeogenesis

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Pharmacology & Pharmacy 2014年第1期5卷 19-23页

作者： Koichi Matsuda yoko horikawa Yasuto Sasaki Shigeko F. Sakata Faculty of Nutrition Kobe Gakuin University Kobe Japan.

Intraperitoneal administration of the non-selective adenosine receptor agonist 5’-N-ethylcarboxamide-adenosine (NECA) (0.1 or 0.3 mg/kg) increased fasting serum glucose levels in mice. To clarify the mechanism responsible for this, the expression of liver glucose 6-phosphatase (G6Pase: a gluconeogenic enzyme) was analyzed, and it was found that G6Pase mRNA was increased by NECA treatment. Administration of 0.3 mg/kg NECA resulted in elevated serum glucose levels at 1 h and were further elevated at 6 h. Administration of 0.1 mg/kg NECA increased serum glucose levels at 1 h and had returned to control levels by 6 h. The increase in fasting serum glucose levels induced by NECA are thought to be caused, in part, by elevated G6Pase expression.

关键词： 5’-N-Ethylcarboxamide-Adenosine Glucose 6-Phosphatase Gluconeogenesis

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Myricetin and Hesperidin Inhibit Cerebral Thrombogenesis and Atherogenesis in Apoe-/-and Ldlr-/-Mice

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Food and Nutrition Sciences 2018年第1期9卷 20-31页

作者： Yasuto Sasaki Kanae Hyodo Ayana Hoshino Eri Kisa Koichi Matsuda yoko horikawa John C. Giddings Laboratory of Physiology Faculty of Nutrition Kobe Gakuin University Kobe Japan Laboratory of Biochemistry Faculty of Nutrition Kobe Gakuin University Kobe Japan Department of Haematology School of Medicine Cardiff University Cardiff UK

Flavonoids have been reported to possess strong antioxidant activities that moderate endothelial dysfunction and demonstrate protective effects on cardiovascular disease. Our previous studies confirmed that flavonoids, including hesperidin, naringin and nobiletin, inhibited thrombogenesis and hypertension in stroke prone spontaneously hypertensive rats (SHRSP) by protecting the endothelium from the adverse effects of free radical formation. We have now further investigated the protective effects of myricetin and hesperidin on cerebral thrombosis and atherogenesis in apolipoprotein E (apoE) and lowdensity lipoprotein receptor (LDLR) deficient (Apoe-/- and Ldlr-/- double knockout) mice. Three groups of mice were fed high fat diet alone and high fat diet mixed with myricetin (100 mg/kg/day and 200 mg/kg/day) or glucosyl hesperidin (G-hesperidin;250 mg/kg/day and 500 mg/kg/day) for 8 weeks. There were no differences in body weight related to administration of the flavonoids. Thrombotic tendency was assessed using a He-Ne laser technique in the murine cerebral pial vessels. In addition, atherogenesis was quantified histologically after dissection of the aorta from each mouse and staining with Oil Red O solution. The percentages of stained area to whole area of dissected aorta were calculated as indices of anti-atherogenic activity. Both myricetin and G-hesperidin significantly inhibited thrombogenesis in vivo and significantly inhibited atherogenesis compared to control mice (p < 0.001). These findings demonstrated that daily intake of myricetin and hesperidin suppressed the development of atherogenesis and thrombogenesis, possibly associated with the potent antioxidant effects of the flavonoids.

关键词： Myricetin Hesperidin Atherosclerosis Apoe-/- and Ldlr-/- Mice Thrombosis

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Magnetic Properties of Nd-Fe-B Sintered Magnet Powders Recovered by Yb Metal Vapor Sorption

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Journal of Rare Earths 2004年第1期22卷 152-156页

作者： horikawa T Itoh M Suzuki Shunji Machida K Collaborative Research Center for Advanced Science and Technology Collaborative Research Center for Advanced Science and TechnologyCollaborative Research Center for Advanced Science and TechnologyCollaborative Research Center for Advanced Science and Technology Osaka University Osaka 565-0871 Japan Osaka University Osaka 565-0871 Japan Osaka University Osaka 565-0871 Japan Osaka University Osaka 565-0871 Japan

Fine ground powders of Nd-Fe-B sintered magnet bulks (particle size=46～125 μm in diameter) were coated and alloyed with Yb metal by sorbing them. A significant recovery of the decreased magnetic properties of the ground powders (remanence B r=～0.95 T, coercivity H cj =～227 kA·m -1 and maximum energy product (BH) max=～48 8 kJ·m -3) was observed in accordance with increasing temperature up to 800 ℃. The sorbing temperature and time for Yb metal vapor were optimized and after heating at 800 ℃ for 90 min and annealing subsequently at 610 ℃ for 60 min, the B r, H cj and (BH) max values were increased to be 0.98 T, 712 kA·m -1 and 173 kJ·m -3, respectively. From the microstructural characterizations of resulting samples by using X-ray diffraction (XRD), scanning electron microscopy (SEM), and electron probe X-ray microanalyzer (EPMA), it is found that the sorbed Yb metal uniformly covers the surface and diffuses to the Nd-rich grain boundary of fine ground powders of Nd-Fe-B sintered magnet bulks forming a (Nd,Yb)Fe 2 phase.

关键词： metal materials Nd 2Fe 14B sintered magnets metal vapor sorption magnetic properties recovery rare earths

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Synthesis and luminescent properties of low oxygen contained Eu^(2+)-doped Ca-α-SiAlON phosphor from calcium cyanamide reduction

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Journal of Rare Earths 2008年第2期26卷 198-202页

作者： PIAO Xianqing Ken-ichi Machida Takashi horikawa Hiromasa Hanzawa Center for Advanced Science and Innovation Osaka University 2-1 Yamadaoka Suita

A new convenient calcium cyanamide （CaCN2） reduction route was developed to synthesize the Eu^2＋ activated Ca-α-SiAION phosphors containing low oxygen content. The luminescence properties of the obtained products were investigated for white LEDs application. The critical Eu^2＋ concentration in various hosts and its effect on the photoluminescence properties were studied. The optimized sample （10at.% Eu^2＋ vs. Ca^2＋） could be efficiently excited by the current GaN/InGaN blue LED chips and provided emission intensity competitive with that of YAG：Ce^3＋（P46-Y3） standard, revealing that this phosphor was a potential candidate for phosphor-converted white LEDs.

关键词： nitride phosphor white LEDs SiAION Eu^2+ CaCN2 rare earths

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Reliability of urinary tests for antibody to Helicobacterpylori in patients with pulmonary tuberculosis

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World Journal of Gastroenterology 2005年第3期11卷 412-414页

作者： Takatsugu Yamamoto Taro Ishii Tomotaka Kawakami yoko Sase Chiaki horikawa Nozomu Aoki Masaki Sanaka Yasushi Kuyama Department of Internal Medicine Hospital attached to the Institute of Chemotherapy

AIM: Although the quality of currently available urinary tests for detecting antibody to Helicobacter pylori (H pylori)have been proved in some populations, the accuracy has not been studied regarding patients who suffer from pulmonary tuberculosis with multi-drug treatments. The present study was conducted to evaluate the accuracy of these urinary tests for antibody to H pylori in these ***: Serum samples from 61 inpatients with pulmonary tuberculosis were tested using enzyme immunoassay, and urine samples were assayed by enzyme-linked immunosorbent assay method (URINELISA) and immunochromatography method (RAPIRAN). Medicines prescribed to the patients were recorded for medical charts, to evaluate the influences on the results of urinary ***: The sensitivity, specificity, and consistency of URINELISA against the serum test were 93.1%, 65.6%, and 78.6% respectively, and those of RAPIRAN were 86.2%,93.7%, and 90.1% respectively, which were almost equal to the data previously reported. Prescribed medicines had little influence on the ***: The two urinary tests for detecting H pylori antibody have a diagnostic accuracy in patients with pulmonary tuberculosis given multiple anti-tuberculosis drugs.

关键词：泌尿系统测试抗体祛痰药肺结核

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Indian monsoon variability in the Mahanadi Basin over the last two glacial cycles and its implications on the Indonesian throughflow

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Geoscience Frontiers 2023年第1期14卷 215-229页

作者： Jongmin Lee Sunghan Kim Minoru Ikehara Keiji horikawa Yoshihiro Asahara Chan Min Yoo Boo-Keun Khim Department of Oceanography Pusan National UniversityBusan 46241South Korea Deep-sea Mineral Resources Research Center Korea Institute of Ocean Science&TechnologyBusan 49111South Korea Division of Glacial Environment Research Korea Polar Research InstituteIncheon 21990South Korea Center for Advanced Marine Research Kochi UniversityKochi 783-8502Japan Graduate School of Science and Engineering for Research University of ToyamaToyama 930-8555Japan Department of Earth and Planetary Sciences Nagoya UniversityNagoya 464-8601Japan

The orbital-scale variability of the Indian summer monsoon(ISM)has been influenced by multiple factors,such as atmospheric CO_(2)concentration,global ice volume,and *** for weathering activity and paleo-productivity provide potential insights into the driving forces of its *** documented multi-proxy data at IODP Site U1445,located in the Mahanadi Basin of the northwestern Bay of Bengal,to find out ISM variability over the last 200 *** proxy records,such as Nd/Sr isotopes of detrital particles,clay mineral compositions of the fine-grained sediments,biogenic opal and CaCO_(3),organic carbon contents,and carbon isotopes of organic matter,represent sediment sources,weathering patterns,and paleo-productivity related to the ISM *** Nd/Sr isotope data and clay mineral compositions suggest that the sediments at Site U1445 originated mainly from the Ganges,Brahmaputra,and Meghna rivers without dramatic provenance change between the glacial and interglacial *** weathering activity inferred from clay mineral compositions and the paleo-productivity shift reconstructed by biogenic opal and CaCO_(3)contents suggest that the land-sea interactions were closely linked to the ISM precipitation between the glacial and interglacial *** precipitation by the strong ISM resulted in intense chemical weathering and dominant biogenic opal deposition during the interglacial *** contrast,low precipitation by the weak ISM led to reduced chemical weathering and predominant CaCO_(3)deposition during the glacial ***,the ISM variability driving the land-sea interactions in the Mahanadi Basin was modulated by the Indonesian throughflow(ITF).Our study emphasizes the role of low-latitude forcing of climatic changes in the strong relationship between the ISM and ITF over orbital periods,providing a base for future investigations.

关键词： Provenance Weathering activity Paleo-productivity Indian summer monsoon Bay of Bengal Indonesian throughflow

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High-density and wide-bandwidth optical interconnects with silicon optical interposers [Invited]

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Photonics Research 2014年第3期2卷 S0001-S0007页

作者： Yutaka Urino Tatsuya Usuki Junichi Fujikata Masashige Ishizaka Koji Yamada Tsuyoshi horikawa Takahiro Nakamura Yasuhiko Arakawa Institute for Photonics-Electronics Convergence System Technology(PECST) Japan Photonics Electronics Technology Research Association(PETRA) West 7 SCR16-1 OnogawaTsukubaIbarakiJapan National Institute of Advanced Industrial Science and Technology West 7 SCR16-1 OnogawaTsukubaIbarakiJapan Institute of Industrial Science The University of Tokyo4-6-1KomabaMeguroTokyoJapan

One of the most serious challenges facing exponential performance growth in the information industry is the bandwidth bottleneck in interchip *** propose a photonics–electronics convergence system in response to this *** demonstrate the feasibility of the system,we fabricated a silicon optical interposer integrated with arrayed laser diodes,spot-size converters,optical splitters,optical modulators,photodetectors,and optical waveguides on a single silicon *** this system,20 Gbps error-free data links and a 30 Tbps∕cm2 bandwidth density were *** bandwidth density is sufficient to meet the interchip interconnect requirements for the late 2010s.

关键词： optical system exponential

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Single-nucleotide polymorphisms in HORMAD1 may be a risk factor for azoospermia caused by meiotic arrest in Japanese patients

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Asian Journal of Andrology 2012年第4期14卷 580-583页

作者： Toshinobu Miyamoto Aldra Tsujimura Yasushi Miyagawa Eitetsu Koh Mikio Namiki Michiharu horikawa Yasuaki Saijo Kazuo Sengoku Department of Obstetrics and Gynecology Asahikawa Medical University Asahikawa Hokkaido 078-8510 Japan Department of Urology Osaka University Graduate School of Medicine Suita 565-0871 Japan Department of Integrated Cancer Therapy and Urology Kanazawa University Graduate School of Medical Science Kanazawa 920-1192 Japan Division of Community Medicine and Epidemiology Department of Health Science Asahikawa Medical University Asahikawa 078-8510 Japan

Genetic mechanisms are implicated as a cause of some male infertility, yet are poorly understood. Meiosis is unique to germ cells and essential for reproduction. The synaptonemal complex is a critical component for chromosome pairing, segregation and recombination. Hormadl is essential for mammalian gametogenesis as knockout male mice are infertile. Hormadl-deficient testes exhibit meiotic arrest in the early pachytene stage and synaptonema! complexes cannot be visualized. To analyze the hypothesis that the human HORMAD1 gene defects are associated with human azoospermia caused by meiotic arrest, mutational analysis was performed in all coding regions by direct sequence analysis of 30 Japanese men diagnosed with azoospermia resulting from meiotic arrest. By the sequence analysis, three polymorphism sites, Single Nucleotide Polymorphism 1 （c. 163A〉G）, SNP2 （c. 501T〉G） and SNP3 （c. 918C〉T）, were found in exons 3, 8 and 10. The 30 patients with azoospermia and 80 normal pregnancy-proven, fertile men were analyzed for HORMAD1 polymorphisms. Both SNP1 and SNP2 were associated with human azoospermia caused by complete early meiotic arrest （P〈0.0S）. We suggest that the HORMAD1 has an essential meiotic function in human spermatogenesis.

关键词： azoospermia HORMAD1 male infertility male meiosis SNP

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