Evaluating the Sensitivity of Mycobacterium tuberculosis to Biotin Deprivation Using Regulated Gene Expression

In the search for new drug targets, we evaluated the biotin synthetic pathway of Mycobacterium tuberculosis (Mtb) and constructed an Mtb mutant lacking the biotin biosynthetic enzyme 7,8-diaminopelargonic acid synthase, BioA. In biotin-free synthetic media, ΔbioA did not produce wild-type levels of biotinylated proteins, and therefore did not grow and lost viability. ΔbioA was also unable to establish infection in mice. Conditionally-regulated knockdown strains of Mtb similarly exhibited impaired bacterial growth and viability in vitro and in mice, irrespective of the timing of transcriptional silencing. Biochemical studies further showed that BioA activity has to be reduced by approximately 99% to prevent growth. These studies thus establish that de novo biotin synthesis is essential for Mtb to establish and maintain a chronic infection in a murine model of TB. Moreover, these studies provide an experimental strategy to systematically rank the in vivo value of potential drug targets in Mtb and other pathogens

Quantification des risques de contamination et d’exposition externe du personnel en radiothérapie interne vectorisée par iode-131

Afin de quantifier les sources d’exposition et de contamination induites par les patients traités à l’iode-131 sur le personnel, nous réalisons au cours de l’hospitalisation des mesures de débit de dose et de contamination atmosphérique, surfacique et cutanée sur douze patients recevant une activité de 3,7 GBq, six ayant bénéficié d’une stimulation par TSHr et six par sevrage d’hormone thyroïdienne. Les valeurs maximales sont mesurées à t = 4 h après la prise d’iode, avec en moyenne, un débit de dose à 1 mètre de 133 μSv h-1, une concentration salivaire de 8,8 MBq g-1, une activité surfacique cutanée de 46 Bq cm-2, une concentration atmosphérique de 183 Bq m-3 et une contamination des sols inférieure à 0,5 Bq cm-2. Les mesures montrent une grande variabilité entre les patients, résultant des différences individuelles physiologiques d’élimination de l’iode-131 et de l’application inégale des consignes d’hygiène. Les contaminations dans l’air de la chambre ont un impact dosimétrique faible par rapport à l’exposition externe provenant du patient mais elles peuvent expliquer les contaminations internes du personnel. Les consignes sont donc de limiter les passages dans la chambre lors des 24 premières heures et faire appliquer de façon stricte les consignes d’hygiène pour tous les patients

Bisphenol A differentially affects male reproductive function biomarkers in a reference population and agro pesticides users from Djutitsa, Cameroon

The consequences of bisphenol A (BPA) exposure on male reproductive function were studied in two populations from Cameroon, farmers using agro pesticides in Djutitsa (rural area) and townsmen in Yaounde (urban area, Centre region). Urinary BPA concentration from all participants was measured, and the values were correlated with biochemical markers of male reproductive function. The data showed that BPA could be detected in 92.6% of urine participants, with an average concentration of 2.18 +/- 1.97 microg/g creatinine but with no significant difference between the urinary BPA concentration from rural and urban populations. From BPA urinary concentration, the BPA average daily intake was estimated to be 0.06 +/- 0.05 mug/kg/day (3.51 microg/day per individual) in the Cameroon population. Interestingly, free and bioavailable testosterone concentrations and estradiol/testosterone ratio correlated with BPA levels in the overall population. When data were analysed according to residence, BPA correlated with total testosterone levels ( r = -0.433) and estradiol/testosterone ratio ( r = 0.338) in the urban residents only, while the rural population exhibited significant increases in sex-hormone-binding globulin with increased BPA exposure. Our data showed that the male Cameroon population is exposed to BPA but that inconstant BPA association to endocrine reproductive markers suggests that other environmental factors in combination with BPA exposure might influence testicular function

A dietary supplement to improve the quality of sleep: a randomized placebo controlled trial

<p>Abstract</p> <p>Background</p> <p>To evaluate the effect of a dietary supplement containing polyunsaturated fatty acids, in association with <it>Humulus lupulus </it>extract, on the quality of sleep using the Leeds sleep evaluation questionnaire (LSEQ) in subjects with moderate to severe sleep disorders.</p> <p>Methods</p> <p>Randomized placebo-controlled trial, in a Population-based setting. Participants were adult patients 25 to 65 years old with a chronic primary insomnia who volunteered for the study. The tested intervention consisted of two soft gelatine capsules per day, containing either the dietary supplement (active group) or olive oil (placebo group) for a month. Subjects could also volunteer for two ancillary studies on melatonin and actigraphy. Evaluation criteria included i) perception of the quality of sleep at the end of treatment using the LSEQ questionnaire, ii) sleep efficiency measured by one-week actigraphic movement measurement performed before and during the treatment in a subsample of subjects, iii) night melatonin and 6 sulfatoxymelatonin (aMT6S) urine rates in a subsample of subjects.</p> <p>Results</p> <p>The average of Leeds score was similar in both groups (p = 0.95). A marked improvement in the quality of sleep was observed in both placebo (62%) and active (65%) group (p = 0.52). The evolution of urinary melatonin, aMT6S, and of the Mel/aMT6S ratio showed no differences between the two groups. Sleep efficiency, as measured by actigraphy, improved similarly in both groups during the treatment period, from 72% to 76% and 75% in the active and placebo group respectively (p = 0.91).</p> <p>Conclusions</p> <p>The dietary supplement had neither effect on the perceived quality of sleep, nor on the melatonin metabolism and sleep-wake cycle.</p> <p>Trial registration: clinical trials.gov:NCT00484497</p