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.
Objective: The objective of this study was to evaluate the impact of an asthma continuing education program on pharmacists’ knowledge and attitudes related to asthma pharmaceutical care. Subjects and Methods: A 20-hour continuing education program was conducted by the joint efforts of the Taipei City Government, Taiwan Association of Asthma Education and Taipei Medical University Wan Fang Hospital, in a series of 4 days afternoon sessions from June 26 to July 4, 2004. One hundred and twenty-five pharmacists participated. The Asthma Knowledge Test in Mandarin and the Asthma Attitude Scale in Mandarin were developed by adapting the scale used to evaluate the impact of pharmacist continuing education programs on diabetic care. The results before and after the intervention were compared to evaluate the impact of the program. Results: Of the 125 participants, 105 returned both the pre- and post-intervention questionnaires, for a response rate of 84.0%. The total score of the attitude section increased significantly from 40.04 ± 3.35 to 42.54 ± 2.98 (full score = 50, p < 0.001). The total score of the knowledge section also increased significantly from 7.18 ± 1.31 to 7.56 ± 1.15 (p = 0.008). Improvement in the attitude score was found in 70 (67.0%) subjects, and in the knowledge score in 45 (43.5%) subjects. Conclusion: The study demonstrated that attitude and knowledge toward asthma care improved after the continuing education program. Further study of long-term impact and direct changes in asthma pharmaceutical care practice will be necessary.
Background and PurposePatients with chronic obstructive pulmonary disease (COPD) are at higher risk of stroke than those without COPD. This study aims to explore the impact of inhaled pharmacotherapy on stroke risk in COPD patients during a three-year follow-up, using a nationwide, population-based study and a matched cohort design.MethodsThe study cohort comprised 10,413 patients who had received COPD treatment between 2004 and 2006; 41,652 randomly selected subjects comprised the comparison cohort. Cox proportional hazard regressions and two-stage propensity score calibration were performed to determine the impact of various inhaled therapies including short-acting muscarinic antagonists, long-acting muscarinic antagonists, short-acting β-agonists (SABAs), long-acting β-agonists (LABAs), and LABA plus inhaled corticosteroid (ICS), on the risk after adjustment for patient demographic characteristics and comorbid disorders.ResultsOf the 52,065 sampled patients, 2,689 (5.2%) developed stroke during follow-up, including 727 (7.0%) from the COPD cohort and 1,962 (4.7%) from the comparison cohort (p < 0.001). Treatment with SABA was associated with 1.67-fold (95% CI 1.45–1.91; p < 0.001) increased risk of stroke in COPD patients. By contrast, the cumulative incidence of stroke was significantly lower in those treated with LABA plus ICS than those treated without (adjusted hazard ratio 0.75, 95% CI 0.60–0.94, p = 0.014).ConclusionsAmong COPD patients, the use of inhaled SABA is associated with an increased risk of stroke, and combination treatment with inhaled LABA and ICS relates to a risk reduction. Further prospective research is needed to verify whether LABA plus ICS confers protection against stroke in patients with COPD.
This study investigates the signaling pathway involved in inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) release caused by Staphylococcus aureus lipoteichoic acid (LTA) in RAW 264.7 macrophages. A phosphatidylcholine-phospholipase C (PC-PLC) inhibitor (D-609) and a phosphatidylinositol-phospholipase C (PI-PLC) inhibitor (U-73122) attenuated LTA-induced iNOS expression and NO release. Two PKC inhibitors (Go 6976 and Ro 31-8220), an NF-kappaB inhibitor (pyrrolidine dithiocarbamate; PDTC), and long-term (24 h) 12-phorbol-13-myristate acetate (PMA) treatment each also inhibited LTA-induced iNOS expression and NO release. Treatment of cells with LTA caused an increase in PKC activity; this stimulatory effect was inhibited by D-609, U-73122, or Ro 31-8220. Stimulation of cells with LTA caused IkappaB-alpha phosphorylation and IkappaB-alpha degradation in the cytosol, and translocation of p65 and p50 NF-kappaB from the cytosol to the nucleus. Treatment of cells with LTA caused NF-kappaB activation by detecting the formation of NF-kappaB-specific DNA-protein complexes in the nucleus; this effect was inhibited by Go 6976, Ro 31-8220, long-term PMA treatment, PDTC, L-1-tosylamido-2-phenylethyl chloromethyl ketone (TPCK), and calpain inhibitor I. These results suggest that LTA might activate PC-PLC and PI-PLC to induce PKC activation, which in turn initiates NF-kappaB activation, and finally induces iNOS expression and NO release in RAW 264.7 macrophages.
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