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.     

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.     

RFa-related peptides are algogenic: evidence in vitro and in vivo

RFamide (RFa)-related peptides modulate pain processing in the mammalian CNS. The effects of these peptides are generally considered as 'anti-opioid'. They also decrease the rate of desensitization of acid-sensing ionic channels (ASICs), putative nociceptors in dorsal root ganglia neurons [C. Askwith et al. (2000) Neuron, 26, 133-141]. We have tested the role of mollusc-derived peptide, FMRFa (Phe-Met-Arg-Phe-amide) and its synthetic analogues in peripheral nociception. Here we demonstrate that RFa-related peptides powerfully excite the majority of C-fibres in the skin-nerve preparation of rat: 76% of 55 tested fibres with the conduction velocity below 2 m/s responded with long-lasting discharges to the application of peptides (20 microm). When injected subcutaneously in vivo (mice), they initiate nociceptive behaviour. We confirm the data on humans [S. Ugawa et al. (2002) J. Clin. Invest., 110, 1185-1190]: the activation of C-fibres by acid is inhibited by channel blocker of ASICs, amiloride. However, there is no correlation in the sensitivity of C-fibres to RFa peptides, protons and amiloride: 74% of tested RFa-sensitive C-fibres were insensitive to protons and in 67% of cases the response to peptides was insensitive to amiloride. Thus, powerful excitatory/algogenic action of RFa-related peptides cannot be interpreted solely in terms of their interaction with ASICs. The peptides do not activate any conductance in the somatic membrane of dorsal root ganglion neurons of rats and probably affect still unidentified molecular target(s) responsible for nociceptive signalling.     

Long-term nutritional and digestive consequences of pelvic radiation

OBJECTIVE: To study long-term changes in nutritional status and gastrointestinal (GI) functions of 15 women previously treated with radiotherapy for gynecological cancer. Two years prior to this research, these patients had been assessed twice: before external radiotherapy and 5 weeks later, at the completion of the external dose (45-50 Gy). METHODS: Each patient was given complete clinical evaluation, consisting of dietary, physical activity and digestive symptoms questionnaires. Blood was drawn for routine clinical laboratory tests (hemoglobin, white blood cell count, creatinine, lipoproteins, glucose, total proteins, albumin, and C reactive protein). Body composition was assessed by classical anthropometric indicators and double beam X-ray absorptiometry (DEXA), while muscle strength was measured through a hand dynamometer. Resting energy expenditure (REE), obtained by indirect calorimetry, was subtracted from energy ingestion, derived from dietary records, to calculate energy balance. RESULTS: This third evaluation included fifteen patients. A significant increase in body mass index (BMI), % body fat and waist circumference were observed in comparison to earlier evaluations. The lean compartment decreased significantly, and REE descended in parallel. Meanwhile, total energy, fat and protein intake increased, compared to previous measurements. The changes in bowel habits observed during radiotherapy persisted at this third evaluation, with the exception of diarrhea, which was less reported. Abdominal bloating and rectal symptoms were the most prevalent complaints. CONCLUSIONS: After radiation treatment for gynecological cancer, patients gained more body fat than expected in Chilean women around menopause. In spite of high protein ingestion, the loss of fat-free mass observed during radiation treatment was not recovered along with weight increase. This is probably associated with infrequent physical activity, both during and after treatment, and hyperphagia.     

Multiple-marker screening in human immunodeficiency virus-positive pregnant women: Screen positivity rates with the triple and quad screens

OBJECTIVE: The study was undertaken to determine the screen-positive rates of multiple-marker screening tests in pregnant women who are positive for human immunodeficiency virus (HIV) at our institution for open neural tube defects and aneuploidy, for both triple (alpha-fetoprotein, human chorionic gonadotropin [hCG], unconjugated estriol) and quad (alpha-fetoprotein, hCG, unconjugated estriol, inhibin A) screens, and to compare these rates with a matched control group. STUDY DESIGN: A 1:1 matched case-control study was performed comparing multiple marker screening test results in 34 HIV-positive women with age- and race-matched HIV-negative controls. Individual serum markers and screen positive rates for both the triple and quad screens were compared among the cases and controls. RESULTS: In each group, there were 19 women with triple screens and 15 with quad screens. Serum hCG multiples of the median were significantly higher in the HIV-positive compared with the HIV-negative women (P=.033). There was no difference in screen positive rates between the cases and controls using the triple screen, but there was a significantly higher overall screen positive rate in the HIV-positive group when the quad screen was used (33% vs 7%, P=.046). CONCLUSION: There is a significantly higher rate of overall quad screen positivity on multiple-marker screening among HIV-positive women compared with a matched control group.