Stevioside is a sweet-tasting glycoside occurring abundantly in the leaves of Stevia rebaudiana (Compositae). It has been used popularly in Japan and Brazil as a sugar substitute for decades. Previous study has shown that it lowered blood pressure in spontaneously hypertensive rats (SHRs) when administered intravenously. This study shows that intraperitoneal injection of stevioside 25 mg/kg also has antihypertensive effect in SHRs. In isolated aortic rings from normal rats, stevioside could dose-dependently relax the vasopressin-induced vasoconstriction in both the presence and absence of endothelium. However, stevioside had no effect on phenylephrine- and KCl-induced phasic vasoconstriction. In addition, stevioside lost its influence on vasopressin-induced vasoconstriction in Ca(2+)-free medium. The results indicate that stevioside caused vasorelaxation via an inhibition of Ca(2+) influx into the blood vessel. This phenomenon was further confirmed in cultured aortic smooth muscle cells (A7r5). Using 10(-5) M methylene blue for 15 min, stevioside could still relax 10(-8) M vasopressin-induced vasoconstriction in isolated rat aortic rings, showing that this vasorelaxation effect was not related to nitric oxide. The present data show that the vasorelexation effect of stevioside was mediated mainly through Ca(2+) influx inhibition.
Combining a EGFR TKI with BEV extended PFS and protected against brain metastasis. Those effects were probably due to the reduction of circulating S100A9-positive MDSCs by BEV, which leads to restoration of effective antitumor immunity. Our data also support the rationale for a BEV-immune checkpoint inhibitor combination.
As smoking significantly inhibits the effectiveness of TB treatment, the integration of smoking cessation into TB treatment programs is strongly advocated to reduce the dual global burden of smoking and TB.
Minimal inhibitory Concentrations (MIC) of 5 antituberculosis drugs (isoniazid, rifampin, streptomycin, ethionamide, and ethambutol) were determined by the radiometric (BACTEC) broth method and by the agar plate proportion method. Seventeen M. tuberculosis strains, isolated from patients before treatment, were tested. The MIC values of 4 of the 5 drugs (the exception was streptomycin) were 2 to 4 times lower in 7H12 broth than in 7H11 agar. The broth-determined MIC were also at least 2 to 4 times lower than the achievable serum concentrations. The broth-determined MIC are probably much closer to the true MIC values than those determined in agar plates because of the lower degree of absorption and degradation in the liquid medium. The radiometric broth method is a simple and rapid quantitative method for accurate determination of the MIC values of the antituberculosis drugs. The data obtained in this study will be used for further evaluation of the MIC values as complementary or alternative to the conventional qualitative testing against critical concentrations.
ObjectiveSmoking has been associated with tuberculosis (TB); however, the effects of smoking on the effectiveness of TB treatment remain unclear.Materials and methodsData were retrieved from case notes and interviews of subjects registered in the TB-reporting system from 2010 to 2012. Study cases were defined as subjects with TB-positive sputum cultures, whereas the controls were defined as subjects with non-TB-related pulmonary diseases. Statistical analyses included logistic regression and multivariate Cox proportional hazard regression models.ResultsA total of 245 cases with cultures positive for TB and 114 controls with non-TB-related pulmonary diseases and negative sputum cultures were recruited. Current smokers had the highest failure rate (33%) for TB treatment, and they had the most severe pulmonary lesions based on chest X-ray grading. Current smokers had a 1.36-fold (95% confidence interval 1.03–2.36, P<0.05) higher odds ratio for cultures positive for TB compared with nonsmokers. In subjects with TB-positive cultures, current smoking was associated with an increase in treatment days required for cultures to convert from positive to negative (hazard ratio 1.12, 95% confidence interval 1.03–1.39; P<0.05).ConclusionLonger periods of treatment may be required for TB patients who are current smokers.
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