Search for methods of lowering the consumption of chlorosulfonic acid in the production of sulfanilamide drugs

Pharmaceutical Chemistry Journal -     

HIV and infant feeding in resource-rich settings: considering the clinical significance of a complicated dilemma

With advances in the care of HIV-positive pregnant women, the likelihood of perinatal transmission is now less than 1%. In resource-rich settings women are instructed to abstain from breastfeeding, as studies have shown that breastfeeding increases the likelihood of infant acquisition of HIV. As practitioners caring for HIV-positive parents, we are now facing growing tension about the complex issues that inform decisions about infant feeding. In the face of changing guidelines and global immigration patterns, simply telling women that breastfeeding is contraindicated may no longer be good enough. We must fully open the lines of communication regarding this important and evolving issue. This commentary will review the clinical, social and cultural considerations that impact decisions regarding infant feeding in the context of HIV.     

Adaptive Optimal Designs for Dose-Finding Studies with Time-to-Event Outcomes

We consider optimal design problems for dose-finding studies with censored Weibull time-to-event outcomes. Locally D-optimal designs are investigated for a quadratic dose–response model for log-transformed data subject to right censoring. Two-stage adaptive D-optimal designs using maximum likelihood estimation (MLE) model updating are explored through simulation for a range of different dose–response scenarios and different amounts of censoring in the model. The adaptive optimal designs are found to be nearly as efficient as the locally D-optimal designs. A popular equal allocation design can be highly inefficient when the amount of censored data is high and when the Weibull model hazard is increasing. The issues of sample size planning/early stopping for an adaptive trial are investigated as well. The adaptive D-optimal design with early stopping can potentially reduce study size while achieving similar estimation precision as the fixed allocation design.     

Lignosulfonic acid blocks in vitro fertilization of macaque oocytes when sperm are treated either before or after capacitation

Lignin-derived macromolecules (LDMs) are biologically active compounds that affect a variety of cell-to-cell interactions including the inhibition of fertilization and embryo development in a number of nonmammalian species. The effect of ligno-sulfonic acid (LSA), a highly sulfonated LDM, on cynomolgus macaque sperm-oocyte interaction was evaluated with a zona pellucida binding assay and by in vitro fertilization (IVF). Sperm were treated with LSA (1.5 mg/mL) either before washing or after capacitation. Capacitation included centrifugation through 80% Percoll followed by 2 consecutive washes with medium, overnight incubation, and activation with dibutyryl cyclic adenosine monophosphate and caffeine. The zona binding assay was performed using immature oocytes that had adhered to the center of glass "binding chambers." The number of capacitated sperm that attached to the zona over a 3-minute period was recorded. Sperm attachment was significantly inhibited by LSA as compared to controls whether treatment occurred after capacitation (92.5%; P <.001) or before washing (82.5%; P <.001). When sperm were treated similarly with fucoidin, a sulfated polysaccharide known to inhibit sperm-oocyte interaction, sperm-zona binding was significantly inhibited by postcapacitation treatment but not by prewash treatment. Treatment of sperm with LSA consistently blocked fertilization over 4 IVF cycles both before washing and after capacitation. Fertilization rate for controls was 65% +/- 17%. No LSA-treated sperm were observed on the surface of lightly rinsed oocytes after 4 hours of coincubation. Localization of biotinylated LSA showed labeling over the entire sperm surface with the greatest intensity observed over the head and midpiece. LSA treatment had no effect on the percentage of motile sperm or quality of sperm motility. Due to the antifertility properties of this nontoxic molecule, LSA appears to have potential as a vaginal contraceptive.