Inverse association between soy food consumption, especially fermented soy products intake and soy isoflavone, and arterial stiffness in Japanese men.

Studies on the associations between soy food consumption and arterial stiffness are rare. The aim of the present study was to evaluate their associations in Japanese men. A total of 652 eligible men, aged 35-69 years, who underwent the measurement of brachial-ankle pulse wave velocity (baPWV) as an index of arterial stiffness were evaluated in this cross-sectional study. Information on their lifestyle characteristics, including dietary behavior, was obtained from a structured self-administered questionnaire. The frequency of total soy products as well as fermented and non-fermented soy products intakes was calculated, and the amounts of soy protein and soy isoflavone intakes were also estimated; these were then divided into tertiles and their associations with baPWV values were evaluated using general linear models. Higher frequency of fermented soy products intake was associated with decreased baPWV after adjusting for the multivariable covariates (P value for trend was 0.002, in Model 3). This association did not alter after further adjustment with a biomarker of systemic inflammation (serum high-sensitivity C-reactive protein (hs-CRP)) (P value for trend was 0.001, in Model 4). Total soy isoflavone consumption was also inversely associated with baPWV even after adjusting for multivariable covariates including serum hs-CRP (P value for trend was 0.043, in Model 4); however total soy protein consumption was not. These results demonstrated that greater consumption of soy food, especially fermented soy products and soy isoflavone was associated with reduced arterial stiffness, independent of systemic inflammation, in Japanese men.

Relationships of serum high-sensitivity C-reactive protein and body size with insulin resistance in a Japanese cohort.

BACKGROUND: Impacts of chronic systemic inflammation and body size and their interaction effect on insulin resistance in Asian populations, in whom obesity is less common, are not fully understood. This study evaluated combined relationships of systemic inflammation and body size with insulin resistance in a Japanese cohort. METHODS: We analyzed cross-sectional data from 1,074 eligible subjects (536 men and 538 women) aged 35-69 years who participated in the baseline survey of a cohort study in Tokushima Prefecture, Japan. Systemic inflammation level was assessed by serum high-sensitivity C-reactive protein (hs-CRP), and the degree of insulin resistance and beta-cell function were evaluated by the homeostasis model assessment insulin resistance (HOMA-IR) and beta-cell function (HOMA-ß), respectively. Overweight and obesity were defined as a body mass index (BMI) of 23.0-24.9 kg/m2 and ≥25.0 kg/m2, respectively. Associations between serum hs-CRP (assessed as quartiles and additionally continuous values after log-transformation) and indices of glucose homeostasis were analysed adjusting for probable covariates, including BMI (quartiles). Combined associations of serum hs-CRP (≤median, >median) and body size (normal, overweight, obese) with insulin resistance as well as their interaction effect on insulin resistance were also evaluated. RESULTS: Serum hs-CRP was dose-dependently associated with HOMA-IR, but not HOMA-ß, after adjustment for probable covariates, including BMI. Subjects with obesity and elevated serum hs-CRP (>median) showed a high multivariable-adjusted HOMA-IR value of 1.32 (95% confidence interval (CI) 1.23, 1.41) compared with subjects with normal BMI and low serum hs-CRP (≤median) whose multivariable-adjusted HOMA-IR value was 1.14 (95% CI 1.06, 1.21). The interaction effect between body size (normal, overweight, obese) and serum hs-CRP (≤median, >median) on HOMA-IR was significant (P for interaction <0.001). CONCLUSIONS: Our study suggests that elevated systemic inflammation is dose-dependently associated with increased insulin resistance, independent of the known risk factors, in a Japanese population. Concomitant obesity and elevated systemic inflammation may synergistically contribute to increased insulin resistance.

[Effect of tacrolimus on the pharmacokinetics and glucuronidation of SN-38, an active metabolite of irinotecan].

The present study has investigated the effect of tacrolimus on the pharmacokinetics of an active metabolite of irinotecan (CPT-11), 7-ethyl-10-hydroxy-camptothecin (SN-38) and SN-38 glucuronide (SN-38G) in rats. The effect of tacrolimus on SN-38 glucuronidation was also investigated in human and rat liver microsomes. When tacrolimus (0.5 mg/kg) was intravenously injected in rats 15 min before intravenous injection of CPT-11 (5 mg/kg), tacrolimus decreased the plasma concentration of SN-38G. Tacrolimus significantly decreased the area under plasma concentration-time curve (AUC) of SN-38G without change in the mean residence time. On the contrary, significant changes in the pharmacokinetic parameters of SN-38 were not observed. SN-38 glucuronidation in human and rat liver microsomes was inhibited dose-dependently by the presence of tacrolimus and the 50% inhibition concentration (IC50) values of tacrolimus in rat and human liver microsomes were 10.33 µM and 3.58 µM, respectively. When the inhibition type was determined by Lineweaver-Burk and Dixon plots, the inhibition was noncompetitive and the calculated inhibition constant (Ki) values for rat and human liver microsomes were 12.57 µM and 3.88 µM, respectively. These findings suggest that tacrolimus inhibits UGT1A1-mediated SN-38 glucuronidation. Considering the IC50 and Ki values for tacrolimus, it is likely that tacrolimus does not alter the pharmacokinetics of SN-38 and SN-38G at the clinically used dosages, suggesting the possibility that tacrolimus can use safely for cancer patients with irinotecan chemotherapy.

A simple liquid chromatography-tandem mass spectrometry method for determination of plasma fentanyl concentration in rats and patients with cancer pain.

A fentanyl patch is widely used for the treatment of cancer pain. Its few adverse effects include constipation and drowsiness. The absorption volume of transdermally applied fentanyl may differ according to its site of application and variability in patch adhesion. Since fentanyl is predominantly metabolized by the drug-metabolizing enzyme cytochrome P450 (CYP) 3A4 in the liver, its concentration may vary in cases of physiologically reduced CYP3A4 activity in the liver (liver disease and aging) or on co-administration of drugs. The clinical significance of measuring plasma concentration of fentanyl is high, but conventional methods require complicated processes such as solid-phase extraction and liquid-liquid extraction before the sample is injected into an HPLC system. In this study, a simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for determining plasma fentanyl concentrations by deproteinization with acetonitrile. A recovery test was conducted using an absolute calibration curve to confirm the method's linearity and inter- and intra-day reproducibility. The required plasma volume for detection was reduced from 1 mL in the conventional method to 20 µL in the present study, and a good calibration curve was obtained in the concentration range from 0.05 to 5 ng/mL. These findings suggest that the method for sample preparation and quantification developed in this study are appropriate for measuring fentanyl concentration in human plasma in clinical settings.