Introduction:Hydrogen-rich water (HRW) has been reported to reduce oxidative stress, suppress exercise fatigue, and enhance recovery. However, the molecular mechanisms of its effects on exercise capacity, especially during the early stages of adaptation in physically inactive individuals, remain unclear. Methods:Male 8-week-old C57BL/6 J mice were provided with purified water or HRW for 1, 2, 4, or 6 weeks. Their exercise endurance was assessed using treadmill running distance, and their levels of markers of oxidative stress, inflammation, and muscle damage were analyzed in skeletal muscle at baseline and after exercise at each time point. Results:Mice that consumed HRW for ≥P4 weeks ran significantly longer distances, showed less muscle fatigue, and had lower levels of markers of oxidative stress, inflammation, and muscle damage. Notably, antioxidant gene expression was not high, despite the lower level of oxidative stress, suggesting the possibility that HRW directly scavenges or suppresses reactive oxygen species, independently of antioxidant pathways. Discussion:HRW consumption alleviates oxidative stress and inflammation in skeletal muscle and improves exercise endurance. These findings suggest that the administration of HRW may represent a promising antioxidant strategy to support the initiation of and compliance with exercise programs by physically inactive individuals.
Local therapy is not considered a standard treatment option for patients with high-volume metastatic prostate cancer. Our research group's previous retrospective study indicated potential benefits of local radiotherapy (LRT) for some high-volume metastatic prostate cancer patients, but prospective studies have yet to confirm these findings. We have thus planned a multicenter, open-label, randomized controlled phase III trial to confirm the efficacy of adding LRT to systemic hormonal therapy with androgen deprivation therapy plus an androgen receptor pathway inhibitor in a population of high-volume metastatic prostate cancer patients for whom the hormonal therapy is effective for 6 months. The primary endpoint is failure-free survival, defined as the time from randomization to prostate-specific antigen progression, radiological progression, clinical progression, or death from any cause. We aim to enroll 360 patients from 56 institutions over a 4-year period. This trial is registered at the Japan Registry of Clinical Trials (study no. jRCT1031220676).
Glycyrrhetinic acid (GA) and glycyrrhizin (GL), active ingredients derived from Glycyrrhiza, Glycyrrhizae Radix (The Japanese Pharmacopia), exhibit various pharmacological effects, such as anti-inflammatory and anti-allergic activities, and a side effect of licorice-induced pseudoaldosteronism. GA is also produced as a metabolite of GL in gastrointestinal bacterial flora when Glycyrrhiza-containing Kampo medicines are orally administered. The present study aimed to confirm that a galacturonic-glycyrrhizin (gala-GL), an analog of GL contained in Glycyrrhiza, contributes to gastrointestinal GA production as well as GL. Gala-GL was hydrolyzed to GA by the intestinal flora, although the hydrolysis rate was slower than that of GL. This is the first report to reveal hydrolyzation of gala-GL into GA in the intestinal flora. The gala-GL content in the 16 Kampo extracts containing 1.0-4.0 g/daily dose of Glycyrrhiza and 8 commercially available Shakuyakukanzoto (SKT) products containing 2.0-4.8 g/daily dose of Glycyrrhiza were 2.2-9.5 and 2.9-7.2 mg/daily dose, respectively. The gala-GL contents corresponded to 7.3-10.9% and 8.0-9.4% of the total GL contents (sum of GL and gala-GL) for the Kampo extracts and SKT products, respectively. These results suggest that gala-GL also can be as sources of gastrointestinal GA, although the contents in Glycyrrhiza-containing Kampo medicines and the hydrolytic rate of conversion to GA in intestinal bacterial flora were much smaller than those of GL.
BACKGROUND:Pycsim, a dosing software for linezolid (LZD) based on Bayesian estimation, predicts dosing in the therapeutic drug monitoring (TDM) of LZD. However, its predictive performance, examined using an independent data set with a limited sample size, must be assessed for further external validation before clinical implementation. This multi-institutional study assessed the predictive performance of Pycsim for LZD concentration. The impact of clinical factors on the prediction accuracy was also evaluated. METHODS:A multicenter prospective study across three institutions was conducted to assess the predictive performance of Pycsim using 87 LZD trough concentrations from 30 patients. The predictive performance was assessed based on the observed and Bayesian-predicted concentrations using linear regression, observed/predicted ratios, mean bias error, mean absolute error, and root mean square error. Multivariate logistic regression was used to identify factors influencing predictive accuracy. RESULTS:A strong correlation was observed between measured and Bayesian-predicted trough concentrations (R2 = 0.82). The geometric mean observed/predicted ratio was 0.96, with mean bias error, mean absolute error, and root mean square error of -1.2, 3.3, and 6.0, respectively. The sampling interval (1-7 days) did not affect the prediction accuracy. A multivariate analysis identified body weight <50 kg (odds ratio, 7.76; 95% confidence interval, 1.74-39.74) and oral administration (odds ratio, 9.73; 95% confidence interval, 1.52-89.53) as significant factors associated with reduced prediction accuracy. CONCLUSIONS:Pycsim showed acceptable overall agreement between the Bayesian-estimated and measured trough concentrations, with minimal systematic bias. However, substantial imprecision limits the reliability of patient-level predictions. Predictive accuracy may be reduced in patients with low body weight and in those receiving oral administration, suggesting that careful monitoring is warranted when using Pycsim.
