Increased de novo glutathione production enhances sexual dysfunctions in rats subjected to paradoxical sleep deprivation.

OBJECTIVE: Poor quality of sexual life has been reported secondary to poor sleep or sleep deprivation. Paradoxical sleep is an integral part of the sleep-wakefulness physiology and prolonged paradoxical sleep deprivation (PSD) may even be fatal. The objective of this investigation was to determine if D-ribose-L-cysteine (RibCys) and zinc (Zn) administration can attenuate the effect of PSD on the sexual function of male rats. METHODS: Following acclimatization, 25 male rats were randomly distributed into five groups of 5 rats each. The PSD, PSD+RibCys, PSD+Zn, PSD+RibCys+Zn, and Control groups were sleep-deprived only, sleep-deprived and given 100mg/kg body-weight of pure RibCys, sleep-deprived and given 10mg/kg body weight Zn, sleep-deprived and given a combination of 100mg/kg of RibCys and 10mg/kg of Zn, and given distilled water without sleep deprivation, respectively. PSD lasted for 20 hours per day for 14 days. Subsequently, the sexual behavioral study was carried out and the animals were sacrificed for biochemical assays. RESULTS: Analyses of results show that for animals treated with RibCys or Zn, all sexual parameters such as mount frequency and latency, intromission frequency and latency and ejaculation frequency and latency were significantly improved compared with animals subjected to PSD only. This improvement correlates strongly with serum glutathione (GHS) levels. CONCLUSION: In summary, riboceine increases circulating GHS, which leads to improved sexual function during sleep deprivation.

Genetic sequencing for surveillance of drug resistance in tuberculosis in highly endemic countries: a multi-country population-based surveillance study.

BACKGROUND: In many countries, regular monitoring of the emergence of resistance to anti-tuberculosis drugs is hampered by the limitations of phenotypic testing for drug susceptibility. We therefore evaluated the use of genetic sequencing for surveillance of drug resistance in tuberculosis. METHODS: Population-level surveys were done in hospitals and clinics in seven countries (Azerbaijan, Bangladesh, Belarus, Pakistan, Philippines, South Africa, and Ukraine) to evaluate the use of genetic sequencing to estimate the resistance of Mycobacterium tuberculosis isolates to rifampicin, isoniazid, ofloxacin, moxifloxacin, pyrazinamide, kanamycin, amikacin, and capreomycin. For each drug, we assessed the accuracy of genetic sequencing by a comparison of the adjusted prevalence of resistance, measured by genetic sequencing, with the true prevalence of resistance, determined by phenotypic testing. FINDINGS: Isolates were taken from 7094 patients with tuberculosis who were enrolled in the study between November, 2009, and May, 2014. In all tuberculosis cases, the overall pooled sensitivity values for predicting resistance by genetic sequencing were 91% (95% CI 87-94) for rpoB (rifampicin resistance), 86% (74-93) for katG, inhA, and fabG promoter combined (isoniazid resistance), 54% (39-68) for pncA (pyrazinamide resistance), 85% (77-91) for gyrA and gyrB combined (ofloxacin resistance), and 88% (81-92) for gyrA and gyrB combined (moxifloxacin resistance). For nearly all drugs and in most settings, there was a large overlap in the estimated prevalence of drug resistance by genetic sequencing and the estimated prevalence by phenotypic testing. INTERPRETATION: Genetic sequencing can be a valuable tool for surveillance of drug resistance, providing new opportunities to monitor drug resistance in tuberculosis in resource-poor countries. Before its widespread adoption for surveillance purposes, there is a need to standardise DNA extraction methods, recording and reporting nomenclature, and data interpretation. FUNDING: Bill & Melinda Gates Foundation, United States Agency for International Development, Global Alliance for Tuberculosis Drug Development.