Role of Plasma Protein and Low-Molecular Weight Substances in the Change of Hydroxyl Radical Scavenging Activity in Hemodialysis Patients

While it is well known that hemodialysis (HD) patients with end stage renal failure are exposed to high oxidative stress, there is not a general opinion regarding whether antioxidant activity is high or low in these patients. We evaluated the variation of plasma hydroxyl radical scavenging activity (p-HRSA) by a single-session of HD in 69 patients by using a new system, reactive flow-injection electron spin resonance. And then comparing p-HRSA with their biochemical parameters, we tried to elucidate what components affected p-HRSA in the HD patients. The average of p-HRSA significantly increased after HD and the variation of p-HRSA by HD was correlated with that of plasma total protein (TP). In 5 patients however, their p-HRSA decreased after HD, in spite of increasing TP. In pre-HD, the p-HRSA values and hydroxyl radical scavenging activity of low-molecular weight fraction of plasma were significantly higher in these 5 patients than in patients whose p-HRSA increased after HD. These 5 patients were in an inflammatory state. These findings suggest that p-HRSA is mainly affected by TP, but caution should be exercised in patients who have high p-HRSA before HD and whose p-HRSA does not increase after HD

Effect of Keishibukuryogan, a Japanese Traditional Kampo Prescription, on Improvement of Microcirculation and Oketsu and Induction of Endothelial Nitric Oxide: A Live Imaging Study

Oketsu is a characteristic condition that plays an important role in Kampo, Japanese traditional medicine, and includes multiple aspects of hemodynamic disorders. This study aims to clarify the microcirculation of Oketsu and the pharmacological effect of Keishibukuryogan, an anti-Oketsu Kampo prescription, using live imaging techniques. Oral administration of Keishibukuryogan induced significant vasodilation of murine subcutaneous arterioles compared to the preadministration level. This vasodilatation peaked 60 min after administration and persisted for 90 min. The blood velocity in the subcutaneous capillary was also increased by Keishibukuryogan in generally the same manner. In rat mesenteric arterioles, Keishibukuryogan administration improved microhemodynamic parameters, including the resolution of erythrocyte congestion and the cell-free layer, which are representative of Oketsu pathology. Live imaging revealed an increase of diaminofluorescein-2 diacetate fluorescence, a nitric oxide (NO) specific reagent, in the arterial endothelium following Keishibukuryogan administration. This fluorescence was most remarkable at vascular bifurcations but was present throughout the mesenteric arterioles. This study demonstrates the successful imaging of Oketsu pathology with respect to microcirculation and the anti-Oketsu effects of Keishibukuryogan, namely, vasodilation of arterioles, increased blood velocity, and resolution of erythrocyte congestion. The anti-Oketsu effect of Keishibukuryogan is related to endothelial NO production

Effect of Keishibukuryogan, a Japanese Traditional Kampo Prescription, on Improvement of Microcirculation and Oketsu and Induction of Endothelial Nitric Oxide: A Live Imaging Study

Oketsu is a characteristic condition that plays an important role in Kampo, Japanese traditional medicine, and includes multiple aspects of hemodynamic disorders. This study aims to clarify the microcirculation of Oketsu and the pharmacological effect of Keishibukuryogan, an anti-Oketsu Kampo prescription, using live imaging techniques. Oral administration of Keishibukuryogan induced significant vasodilation of murine subcutaneous arterioles compared to the preadministration level. This vasodilatation peaked 60 min after administration and persisted for 90 min. The blood velocity in the subcutaneous capillary was also increased by Keishibukuryogan in generally the same manner. In rat mesenteric arterioles, Keishibukuryogan administration improved microhemodynamic parameters, including the resolution of erythrocyte congestion and the cell-free layer, which are representative of Oketsu pathology. Live imaging revealed an increase of diaminofluorescein-2 diacetate fluorescence, a nitric oxide (NO) specific reagent, in the arterial endothelium following Keishibukuryogan administration. This fluorescence was most remarkable at vascular bifurcations but was present throughout the mesenteric arterioles. This study demonstrates the successful imaging of Oketsu pathology with respect to microcirculation and the anti-Oketsu effects of Keishibukuryogan, namely, vasodilation of arterioles, increased blood velocity, and resolution of erythrocyte congestion. The anti-Oketsu effect of Keishibukuryogan is related to endothelial NO production

The Japan Public Health Center-based Prospective Study for the Next Generation (JPHC-NEXT): Study Design and Participants

Background: Lifestyle and life-environment factors have undergone drastic changes in Japan over the last few decades. Further, many molecular epidemiologic studies have reported that genetic, epigenetic, and other biomarker information may be useful in predicting individual disease risk.Methods: The Japan Public Health Center-based Prospective Study for the Next Generation (JPHC-NEXT) was launched in 2011 to identify risk factors for lifestyle-related disease, elucidate factors that extend healthy life expectancy, and contribute toward personalized healthcare based on our more than 20 years’ experience with the JPHC Study. From 2011 through 2016, a baseline survey was conducted at 16 municipalities in seven prefectures across the country. A self-administered questionnaire was distributed to all registered residents aged 40–74, which mainly asked about lifestyle factors, such as socio-demographic situation, personal medical history, smoking, alcohol and dietary habits. We obtained informed consent from each participant to participate in this long follow-up study of at least 20 years, including consent to the potential use of their residence registry, medical records, medical fee receipts, care insurance etc., and to the provision of biospecimens (blood and urine), including genomic analysis.Results: As of December 31, 2016, we have established a population-based cohort of 115,385 persons (Response rate 44.1%), among whom 55,278 (47.9% of participants) have provided blood and urine samples. The participation rate was slightly higher among females and in the older age group.Conclusion: We have established a large-scale population-based cohort for next-generation epidemiological study in Japan

Mineralogy and crystallography of some Itokawa particles returned by the Hayabusa asteroidal sample return mission

We studied seven Itokawa particles provided by the Japan Aerospace Exploration Agency (JAXA) as first International Announcement of Opportunity (AO) study mainly using electron and synchrotron radiation X-ray beam techniques. All the analyzed particles were collected from the first-touchdown site and composed of olivine and plagioclase with traces of Ca phosphate and chromite, and do not contain pyroxenes. Optical microscopy of these particles shows minor undulatory extinction of olivine and plagioclase, suggesting minor shock metamorphism (shock stage: S2). The electron microprobe analysis shows that olivine is Fo(70-73) and plagioclase is An(13-10)Or(5-7). The synchrotron radiation X-ray diffraction (SR-XRD) analysis of olivine crystals gives cell dimensions of a = 4.708 to 4.779 angstrom, b = 10.271 to 10.289 angstrom, c = 6.017 to 6.024 angstrom, corresponding to the Fo content of Fo(similar to 70) by Vegard's law. This composition matches the result obtained by the electron microprobe analysis. The olivine compositions of the analyzed particles are consistent with those of LL chondrites. The cell dimensions of two plagioclase crystals (a = 8.180 to 8.194 angstrom, b = 12.53 to 12.893 angstrom, c = 7.125 to 7.23 angstrom, a = 92.6 degrees to 93.00 degrees, beta = 116.36 degrees to 116.75 degrees, gamma = 90.03 degrees to 90.17 degrees) indicate that their equilibration temperatures are 800 degrees C +/- 10 degrees C. This temperature is near the peak metamorphic temperature recorded by equilibrated ordinary chondrites. The size of plagioclase crystals and the homogeneity of olivine compositions indicate that their petrologic type is >= 5. We also analyzed plagioclase by SR iron X-ray absorption near-edge structure (SR-XANES) and found that its Fe3+/(Fe2+ + Fe3+) ratio is approximately 0.5. Such high Fe3+ abundance indicates the formation under a relatively oxidizing environment. Thus, all these analyses have reconfirmed that the Itokawa particles returned by the Hayabusa spacecraft are very weakly shocked equilibrated LL chondrites, which matches the results of the preliminary examination team

Role of nitric oxide in the synthesis of guanidinosuccinic acid, at activator of the N-methyl-d-asparate receptor

Role of nitric oxide in the synthesis of guanidinosuccinic acid, at activator of the N-methyl-d-asparate receptor.BackgroundWe propose that reactive oxygn and arginiosuccinic acid (ASA) form guanidinosuccinic acid (GSA). An alternative to this hypothesis is the so-called guanidine cycle, which consists of a series of hydroxyurea derivatives that serve as intermediates in a pathway leading from urea to GSA. We compare the role of the guanidine cycle to that of nitric oxide (NO) in the synthesis of GSA.MethodsThe members of the guanidine cycle (hydroxyurea, hydroxylamine plus homoserine, L-canaline, and L-canavanine) were incubated with isolated rat hepatocytes. The known NO donors, NOR-2, NOC-7, and SIN-1, were incubated with ASA in vitro. Ornithine, arginine, or citrulline, which increase arginine, a precursor of NO, were incubated with isolated rat hepatocytes. GSA was determined by high-performance liquid chromatography.ResultsNone of guanidine cycle members except for urea formed GSA. SIN-1, which generates superoxide and NO formed GSA, but other simple NO donors, did not. Both carboxy-PTIO, a scavenger, completely inhibited GSA synthesis by SIN-1. GSA formation by SIN-1 reached a maximum at 0.5 mmol/L and decreased at higher concentrations GSA synthesis, stimulated by urea in isolated hepatocytes, was inhibitd by orinithine, arginine, or citrullin with ammonia, but not by ornithine without ammonia, where arginine production is limited.ConclusionGSA is formed ASA and the hydroxyl radical. When arginine increased in hepatocytes, GSA synthesis decreased. These data suggest that increased NO, which results from high concentrations of arginine, or SIN-1, scavanges the hydroxyl radical. This may explain the decreased GSA synthesis in inborn errors of the urea cycle where ASA is decreased, and also the diminished GSA excretion in arginemia