Synthesis of a 35S‐labeled dinucleoside phosphorothioate prodrug,an orally bioavailable anti‐HBV agent

The ³⁵S‐labeled, dinucleoside phosphorothioate 1, an orally available agent against hepatitis B virus, was prepared in eight steps with high specific activity and radiochemical purity. Radiolabeled 3H‐benzodithiole‐3‐one‐1,1‐dioxide was synthesized in four steps from ³⁵S₈ and was used as the sulfurizing reagent. Copyright © 2012 John Wiley & Sons, Ltd.     

Inhibition of STAT3 signaling and induction of SHP1 mediate antiangiogenic and antitumor activities of ergosterol peroxide in U266 multiple myeloma cells

Background  

Ergosterol peroxide (EP) derived from edible mushroom has been shown to exert anti-tumor activity in several cancer cells. In the present study, anti-angiogenic activity of EP was investigated with the underlying molecular mechanisms in human multiple myeloma U266 cells.     

Yoga Training Improves Metabolic Parameters in Obese Boys

Yoga has been known to have stimulatory or inhibitory effects on the metabolic parameters and to be uncomplicated therapy for obesity. The purpose of the present study was to test the effect of an 8-week of yoga-asana training on body composition, lipid profile, and insulin resistance (IR) in obese adolescent boys. Twenty volunteers with body mass index (BMI) greater than the 95th percentile were randomly assigned to yoga (age 14.7±0.5 years, n=10) and control groups (age 14.6±1.0 years, n=10). The yoga group performed exercises three times per week at 40~60% of heart-rate reserve (HRR) for 8 weeks. IR was determined with the homeostasis model assessment of insulin resistance (HOMA-IR). After yoga training, body weight, BMI, fat mass (FM), and body fat % (BF %) were significantly decreased, and fat-free mass and basal metabolic rate were significantly increased than baseline values. FM and BF % were significantly improved in the yoga group compared with the control group (p<0.05). Total cholesterol (TC) was significantly decreased in the yoga group (p<0.01). HDL-cholesterol was decreased in both groups (p<0.05). No significant changes were observed between or within groups for triglycerides, LDL-cholesterol, glucose, insulin, and HOMA-IR. Our findings show that an 8-week of yoga training improves body composition and TC levels in obese adolescent boys, suggesting that yoga training may be effective in controlling some metabolic syndrome factors in obese adolescent boys.     

Effect of dissolved oxygen in alcoholic beverages and drinking water on alcohol elimination in humans

Oxygen plays an important role in the metabolism of alcohol. An increased dissolved oxygen level in alcoholic beverages reportedly accelerates the elimination of alcohol. Therefore, we evaluated the effect of dissolved oxygen in alcohol and the supportive effect of oxygenated water on alcohol pharmacokinetics after the excessive consumption of alcohol, i.e., 540 ml of 19.5% alcohol (v/v). Fifteen healthy males were included in this randomized, 3 × 3 crossover study. Three combinations were tested: X, normal alcoholic beverage and normal water; Y, oxygenated alcoholic beverage and normal water; Z, oxygenated alcoholic beverage and oxygenated water. Blood alcohol concentrations (BACs) were determined by conversion of breath alcohol concentrations. Four pharmacokinetic parameters (C_max, T_max, K_el, and AUCall) were obtained using non-compartmental analysis and the times to reach 0.05% and 0.03% BAC (T_0.05% and T_0.03%) were compared using one-way analysis of variance (ANOVA) and Duncan's post hoc test. With combination Z, the BAC decreased to 0.05% significantly faster (p < 0.05) than with combination X. Analyzing the pharmacokinetic parameters, the mean K_el was significantly higher for combination Z than for combinations X and Y (p < 0.05), whereas the mean values of C_max, T_max and AUCall did not differ significantly among the combinations. Dissolved oxygen in drinks accelerates the decrease in BAC after consuming a large amount of alcohol. However, the oxygen dissolved in the alcoholic beverage alone did not have a sufficient effect in this case. We postulate that highly oxygenated water augments the effect of oxygen in the alcoholic beverage in alcohol elimination. Therefore, it is necessary to investigate the supportive effect of ingesting additional oxygenated water after heavy drinking of normal alcoholic beverages.     

Estimation of 24-Hour Urinary Sodium Excretion Using Spot Urine Samples

The present study evaluated the reliability of equations using spot urine (SU) samples in the estimation of 24-hour urine sodium excretion (24-HUNa). Equations estimating 24-HUNa from SU samples were derived from first-morning SU of 101 participants (52.4 ± 11.1 years, range 24–70 years). Equations developed by us and other investigators were validated with SU samples from a separate group of participants (n = 224, 51.0 ± 10.9 years, range 24–70 years). Linear, quadratic, and cubic equations were derived from first-morning SU samples because these samples had a sodium/creatinine ratio having the highest correlation coefficient for 24-HUNa/creatinine ratio (r = 0.728, p < 0.001). In the validation group, the estimated 24-HUNa showed significant correlations with measured 24-HUNa values. The estimated 24-HUNa by the linear, quadratic, and cubic equations developed from our study were not significantly different from measured 24-HUNa, while estimated 24-HUNa by previously developed equations were significantly different from measured 24-HUNa values. The limits of agreement between measured and estimated 24-HUNa by six equations exceeded 100 mmol/24-hour in the Bland-Altman analysis. All equations showed a tendency of under- or over-estimation of 24-HUNa, depending on the level of measured 24-HUNa. Estimation of 24-HUNa from single SU by equations as tested in the present study was found to be inadequate for the estimation of an individual’s 24-HUNa.