Cholesterol-lowering activity of adzuki bean (Vigna angularis) polyphenols.

BACKGROUND: Adzuki beans (ABs; Vigna angularis) were reported to show potential for prevention of cholesterol absorption and lowering of the blood cholesterol level. However, the main active compounds and some cellular effects remain unknown. In this study, we evaluated the potential cholesterol-lowering effects of (+)-catechin 7-O-ß-D-glucopyranoside (C7G) and (+)-epicatechin 7-O-ß-D-glucopyranoside (E7G), identified as abundant polyphenols in ABs. METHODS AND RESULTS: To investigate the cholesterol-lowering activity in vitro, cholesterol micelles, bile acids, and Caco-2 cells as an intestinal model were used in the study. C7G and E7G each inhibited micellar solubility in a dose-dependent manner, and their inhibitory activity was as strong as that of (+)-catechin (IC50 values: C7G, 0.23 ± 0.03 mg/ml; E7G, 0.22 ± 0.02 mg/ml; (+)-catechin, 0.26 ± 0.11 mg/ml). The AB polyphenols showed binding activity toward bile acids and changed them into an insoluble form. When Caco-2 cells were treated with C7G or E7G, the amount of incorporated cholesterol was significantly decreased compared with vehicle-treated control cells, and no cytotoxicity was observed under the experimental conditions used. Meanwhile, quantitative real-time PCR revealed that the mRNA level of the cholesterol transporter NPC1L1 remained unchanged in the treated cells. CONCLUSIONS: Taken together, the present findings suggest that C7G and E7G are the main active compounds in ABs, and have the ability to inhibit micellar solubility, bind to bile acids, and suppress cholesterol absorption. The present study supports the health benefits of ABs as a medicinal food and the application of AB polyphenols as medicinal supplements to suppress cholesterol elevation.

Time to Recurrence Associated With Poor Prognosis in Japanese Oral Squamous Cell Carcinoma Patients.

Purpose: Recurrence in oral squamous cell carcinoma (OSCC) is not rare. Due to lack of studies assessing characteristics of recurrent OSCC, including time to recurrence and outcomes, we sought to investigate its characteristics, time to recurrence, and outcomes in Japanese OSCC patients. Methods: This study was a nonrandomized retrospective cohort study in a tertiary referral centre. It included 208 (117 men and 91 women) patients with recurrent oral cancer who underwent major curative surgery in the Department of Oral and Maxillofacial Surgery at Kobe University Hospital between January 1999 and April 2017. The outcomes were disease-specific survival (DSS) and overall survival (OS). Results: In multivariable Cox proportional hazards analysis, the time to recurrence (hazard ratio [HR] 3.55, 95% confidence interval [CI] 1.69-6.63; P = 0.001), extranodal extension (ENE, HR 2.72, 95% CI 1.51-4.89; P = 0.001), and high T stage (HR 2.00, 95% CI 1.01-3.97; P = 0.046) were independent predictors of DSS. The time to recurrence (HR 3.29, 95% CI 1.82-5.96; P < 0.001) and ENE (HR 2.64, 95% CI 1.52-4.56; P = 0.001) were independent predictors of OS. Conclusion: Time to recurrence, extranodal extension, and higher T stage were independent prognosis predictors in OSCC.

Pharmacokinetics and safety of 3,4-diaminopyridine base in healthy Japanese volunteers.

OBJECTIVE: 3,4-diaminopyridine (3,4-DAP) is commonly used for treating neuromuscular diseases, such as the Lambert-Eaton myasthenic syndrome, but the pharmacokinetics of 3,4-DAP base have not been investigated. We therefore studied 3,4-DAP base pharmacokinetics in healthy Japanese volunteers. MATERIALS AND METHODS: In this crossover study, we administered a single oral dose of 10 or 20 mg 3,4-DAP base to healthy Japanese volunteers (n = 5) after food intake, or 10 mg 3,4-DAP to fasting individuals. We measured serum 3,4-DAP concentrations, performed electrocardiography (ECG), and administered questionnaires. RESULTS: After administration of 10 or 20 mg 3,4-DAP following food intake, the maximum serum concentrations (Cmax) were 8.09 ± 4.47 ng/mL and 35.8 ± 15.7 ng/mL, respectively (mean ± standard deviation; SD), and the areas under the serum concentration-time curve (extrapolated to infinity) were 639 ± 213 ng x min/mL and 2,097 ± 936 ng x min/mL (mean ± SD), respectively. Administration to fasted individuals indicated that food intake did not significantly alter 3,4-DAP pharmacokinetics. ECG showed no clinically significant changes, but PR intervals were prolonged in all cases. Two out of 5 subjects showed perioral paresthesia symptoms after administration of 20 mg 3,4-DAP. CONCLUSION: This study indicated that 3,4-DAP base pharmacokinetics were non-linear. Although no clinically significant changes in ECG were observed, it is advisable to perform ECG periodically during 3,4-DAP administration in order to monitor cardiac function. Moreover, the development of perioral paresthesia may be dependent on the dose of 3,4-DAP used.

Extension of size of monodisperse silica nanospheres and their well-ordered assembly.

A liquid-phase method for preparing uniform-sized silica nanospheres (SNSs) 12 nm in size and their three-dimensionally ordered arrangement upon solvent evaporation have recently been pioneered by us. Here we report the successful control of the sphere sizes in the wide range from 14 to 550 nm by the seed regrowth method. In this method, the dispersion of SNSs 14 nm in size as seeds was prepared in the emulsion system containing Si(OEt)(4) (TEOS), water and arginine under weakly basic conditions (pH 9-10). An appropriate portion of this dispersion is added to the solution containing water, ethanol and arginine, and then TEOS is added. The additional TEOS introduced into the regrowth system contributed only to the resumed growth of the seeds, not to the formation of new silica particles. The size of interparticle pores was finely tuned by changing the size of the spheres. The preparation of three-dimensionally ordered porous carbons by using the colloidal array of silica nanospheres as a template is also reported.