Exposures of male rats to environmental chemicals [bisphenol A and di (2-ethylhexyl) phthalate] affected expression of several proteins in the developing epididymis.

Hormonally active agents are released into the environment from industrial and manufacturing activity. Evidence in the literature indicates that impaired reproductive capacity in wildlife and laboratory species is associated with chemical exposures. In particular, bisphenol A (BPA) and di (2-ethylhexyl) phthalate (DEHP) have generated public interest due to their presence in several consumer products. In this study, we determined that expression of steroid hormone receptors (estrogen and androgen receptors), Wnt4, and ß-catenin was greater (p < 0.05) in the rat epididymis at 35 days of age compared to 21 and 90 days. Second, timed-pregnant Long-Evans dams were exposed to the chemicals BPA and DEHP by gavage from gestational days 12-21. The caput epididymis was collected from cohorts of male offspring at 35 and 90 days of age and processed for Western blot analysis. Results showed that prenatal BPA and DEHP exposures affected (p < 0.05) expression of estrogen and androgen receptor, Wnt4, ß-catenin, MAPK, and HOXD4 protein in the epididymis. Data have implications for morphological development of the epididymis, a possibility that would be explored in future studies.

Rational design of glycoengineered interferon-ß analogs with improved aggregation state: experimental validation.

Recombinant human interferon-ß (rhIFN-ß) used clinically has lower efficacy than expected due to protein instabilities such as aggregation. Increasing molecular stability, glycoengineering has been used to improve clinical efficacy for a number of therapeutics; however, often labor-intensive trail-and-error approaches are used to identify additional glycosylation sites. In this study two rhIFN-ß analogs with one additional glycosylation site, L6T and S75N, identified by a rational in silico approach, were characterized. These rhIFN-ß analogs were synthesized in parallel with a Chinese hamster ovary (CHO) codon-optimized natural human IFN-ß (Opt-IFN-ß) and expressed in CHO cells using the same expression system. The molecular weights for both analogs were observed to be higher than Opt-IFN-ß, consistent with hyper-glycosylation. The in vitro biological assay showed the hyper-glycosylated analogs and the Opt-IFN-ß had similar activity. The aggregation studies demonstrated that both analogs had lower tendencies to aggregate compared to the Opt-IFN-ß. These experimental studies validate the in silico strategy to predict suitable glycosylation sites that would be glycosylated, while maintaining biological function. Moreover, this work describes hyper-glycosylated rhIFN-ß analogs with improved solubility (i.e. lower aggregation). These findings, together with the rational in silico design, will allow us to increase protein glycosylation with the goal to enhance therapeutic efficacy.

Audio computer-assisted survey instrument versus face-to-face interviews: optimal method for detecting high-risk behaviour in pregnant women and their sexual partners in the south of Brazil.

Audio computer-assisted survey instrument (ACASI) has been shown to decrease under-reporting of socially undesirable behaviours, but has not been evaluated in pregnant women at risk of HIV acquisition in Brazil. We assigned HIV-negative pregnant women receiving routine antenatal care at in Porto Alegre, Brazil and their partners to receive a survey regarding high-risk sexual behaviours and drug use via ACASI (n = 372) or face-to-face (FTF) (n = 283) interviews. Logistic regression showed that compared with FTF, pregnant women interviewed via ACASI were significantly more likely to self-report themselves as single (14% versus 6%), having >5 sexual partners (35% versus 29%), having oral sex (42% versus 35%), using intravenous drugs (5% versus 0), smoking cigarettes (23% versus 16%), drinking alcohol (13% versus 8%) and using condoms during pregnancy (32% versus 17%). Therefore, ACASI may be a useful method in assessing risk behaviours in pregnant women, especially in relation to drug and alcohol use.

[Behavioral disorders secondary to benzodiazepine therapy]. / Troubles comportementaux secondaires à la prise de benzodiazépines.

This report adds three cases to those previously published of paradoxical reactions to benzodiazepines. The clinical syndrome, more or less complete, is fairly stereotyped, with behavioural disorders, tendency to feelings of hostility and aggressiveness and total anterograde amnesia. Personal and environmental factors seem to play a prominent role in its development. The classical contra-indication of benzodiazepines following such reactions is discussed, and the hypothesis that mamillary-thalamic benzodiazepine receptors play a part in their genesis is envisaged.