ABSTRACT
Resveratrol's effect on bone mineral density (BMD) and expression of cytokines in ovariectomized rats (postmenopausal osteoporosis model) was studied. The study was conducted on 3-month-old Sprague-Dawley rats that were (a) sham-operated, (b) ovariectomized, (c) ovariectomized and treated with ß-estradiol (487.5 µg/kg weight/day), and (d) ovariectomized and treated with resveratrol (625 µg/Kg body weight/day). The treatment was for 4 weeks. After sacrifice BMD and gene expression (RANKL, OPG, IL-23, and IL-17A, IL-1ß, and TNFα) were measured in tibia and femur respectively. Resveratrol could restore RANKL/OPG ratio, slightly increase BMD, and moderately but significantly reduce IL-23, IL-17A, IL-1ß, and TNF-α cytokine expression levels.
Subject(s)
Cytokines/drug effects , Osteoporosis, Postmenopausal/drug therapy , Osteoprotegerin/drug effects , RANK Ligand/drug effects , Resveratrol/pharmacology , Animals , Bone Density/drug effects , Disease Models, Animal , Female , Humans , Osteoporosis, Postmenopausal/etiology , Ovariectomy , Rats , Rats, Sprague-DawleyABSTRACT
BACKGROUND: A live oral cholera vaccine VA 1.4 developed from a non-toxigenic Vibrio cholerae O1 El Tor strain using ctxB gene insertion was further developed into a clinical product following cGMP and was evaluated in a double-blind randomized placebo controlled parallel group two arm trial with allocation ratio of 1â¶1 for safety and immunogenicity in men and women aged 18-60 years from Kolkata, India. METHOD: A lyophilized dose of 1.9×109 CFU (nâ=â44) or a placebo (nâ=â43) reconstituted with a diluent was administered within 5 minutes of drinking 100 ml of a buffer solution made of sodium bicarbonate and ascorbic acid and a second dose on day 14. RESULT: The vaccine did not elicit any diarrhea related adverse events. Other adverse events were rare, mild and similar in two groups. One subject in the vaccine group excreted the vaccine strain on the second day after first dose. The proportion of participants who seroconverted (i.e. had 4-folds or higher rise in reciprocal titre) in the vaccine group were 65.9% (95% CI: 50.1%-79.5%) at both 7 days (i.e. after 1st dose) and 21 days (i.e. after 2nd dose). None of the placebo recipients seroconverted. Anti-cholera toxin antibody was detected in very few recipients of the vaccine. CONCLUSION: This study demonstrates that VA 1.4 at a single dose of 1.9×109 is safe and immunogenic in adults from a cholera endemic region. No additional benefit after two doses was seen. TRIAL REGISTRATION: Clinical Trials Registry-India, National Institute of Medical Statistics (Indian Council of Medical Research) CTRI/2012/04/002582.
