Impact of lactational performance on bone mineral density in marginally-nourished Bangladeshi women

This cross-sectional study, carried out during July 1997-June 1998, evaluated the effects of prolonged breast-feeding and lactational amenorrhoea on bone mineral density (BMD) in 400 marginally-nourished Bangladeshi women aged 20-81 years. A bone densitometer was used for measuring BMD in the distal and ultra-distal end of radius and ulna. The results showed that the women who breastfed for 60 months or less had a higher mean BMD compared to those who breastfed for 61-120 months and for over 120 months. There was a significantly higher BMD in the women who had a shorter duration of lactational amenorrhoea compared to those having a longer duration of lactational amenorrhoea. BMD was significantly and negatively correlated with total duration of lactational amenorrhoea (slope -0.024, p<0.05) after controlling for parity, physical workload, and total duration of breast-feeding. The study concluded that there was a negative correlation between longer duration of breast-feeding and BMD, but it was not found when other factors were controlled in multivariate analysis. The duration of lactational amenorrhoea, which is a proxy indicator of breast-feeding, showed a negative correlation with BMD. It is recommended that all lactating women be given diet with adequate calcium to support breast-feeding for maintaining good nutrition of their bones.     

Clinical research in pediatric ophthalmology: the Pediatric Eye Disease Investigator Group

The Pediatric Eye Disease Investigator Group (PEDIG) is a network of university-based and community-based pediatric eye care practitioners that is conducting multiple clinical research studies. The group has conducted the Congenital Esotropia Observational Study, which assessed the early course of esotropia in infants, and the Amblyopia Treatment Studies, a series of randomized trials, the first of which compared atropine and patching for treatment of moderate amblyopia in children 3 to <7 years old. Herein, the results of these studies are summarized, and the current and future studies of the group are described.     

Effect of desogestrel on blood-lipid in relation to its biological activities

Desogestrel (DG), a 19-nor progestin, is widely used in replacement therapy as a contraceptive steroidal hormone. Considering the importance of its partition coefficient parameter (log P = 5.68), a significant contributor to its action mechanism, interactions of the drug with blood-lipids had been investigated using phospholipid binding, fatty acid composition and peroxidation phenomena as the parameters under investigation to explain its pharmacodynamic behavior. From the present investigation, it was observed that lipid loss after incubation of whole blood with DG (80 ng/ml, effective contraceptive concentration in blood) for varying periods of time was accompanied with significant changes in fatty acid composition, which may be ascribed to binding affinity of DG with lipid constituents in blood that may have a role in the mediation of its therapeutic effect. Lipid peroxidation induction potential of DG has been quantitatively measured in the context of its toxicity. The results reveal that DG caused significant extent of lipid peroxidation. Ascorbic acid, an antioxidant, at equivalent human dose of 250 mg could significantly reduce DG-induced lipid peroxidation.     

A portable microkeratome-based anterior corneal surface harvesting device

PURPOSE: To determine the reproducibility of anterior sclerokeratectomy using a portable nonelectric microkeratome-based device capable of harvesting the entire anterior corneal surface for lamellar transplantation. METHODS: A modified gas turbine-driven microkeratome (LSK One, Moria/Microtech, Doylestown, PA) with a redesigned head large enough to incorporate the whole human anterior corneal surface in a pass and was coupled to a manual vacuum pump. This instrument was tested on 25 fresh porcine globes divided into 2 groups (170-microm and 200-microm head). To assess cut reproducibility the physical dimensions (diameter and thickness) of the obtained lenticules were measured. RESULTS: The obtained lenticules were fairly circular (horizontal versus vertical diameters, p >0.2), with average diameters of 12.85 +/- 0.52 mm and 13.25 +/- 1.15 mm for the 170 and 200-microm heads, respectively. The average central lenticule thickness was 176.92 +/- 34.68 microm and 166.00 +/- 53.74 microm for the 170 and 200-microm heads, respectively. CONCLUSION: This new system presents an economical and portable alternative to electric-powered systems. In addition to being used by surgeons in the operating room, eye bank technicians in the field could theoretically use this system; including in developing countries where cost, availability of electricity, and portability are issues.     

Metabolism of 4-fluoroaniline and 4-fluorobiphenyl in the earthworm Eisenia veneta characterized by high-resolution NMR spectroscopy with directly coupled HPLC-NMR and HPLC-MS

1. Little is known about metabolism of xenobiotics by earthworms, despite their importance in soil ecotoxicity testing. Normal earthworms and earthworms treated with antibiotics to ensure inhibition of gut microflora were exposed to two model xenobiotic compounds, 4-fluoroaniline and 4-fluorobiphenyl, to determine which metabolites were produced, and whether the pattern of metabolism was affected by the presence of microbial transformation ability. 2. (19)F-NMR spectroscopy detected the number and relative proportions of metabolites and directly coupled HPLC-(1)H-NMR spectroscopy and HPLC-MS then identified the metabolites. 3. Despite uptake, no metabolism of 4-fluorobiphenyl was observed at any stage, which appears to be a consequence of the lack of oxidative Phase I metabolic activity of the earthworms towards this substrate. In contrast, 4-fluoroaniline exhibited dose-dependent metabolism. At high doses (leading to mortality within 24 h) one predominant metabolite was observed, which was identified as the N-beta-glucoside conjugate. At lower dose levels, the predominant metabolite was the gamma-glutamyl conjugate, although the glucoside and another as yet unidentified metabolite were also detected. 4. The inhibition of gut microflora did not have any influence on metabolism. The study represents the first evidence for glucoside and glutamyl conjugation as a pathway for xenobiotic metabolism in earthworms.     

19F-NMR and directly coupled 19F/1H-HPLC-NMR spectroscopic investigations of the metabolism of the model ecotoxin 3-trifluoromethylaniline in the earthworm species Eisenia veneta

1. The metabolic fate of the model ecotoxin 3-trifluoromethylaniline (3-TFMA) in earthworm was studied by (19)F- and directly coupled (19)F/(1)H-HPLC-NMR spectroscopy. Earthworms of Eisenia veneta spp. were subjected to the ecotoxin during a filter papercontact toxicity test at exposure levels of 1000, 100, 10, 1 and 0.1 micro g cm(-2). A metabolic profile was obtained previously by (19)F-NMR spectroscopy and metabolites were observed at all the exposure levels. 2. Identification of metabolites in individual worm extracts at the (lethal) exposure levels of 1000 and 100 micro g cm(-2) could be achieved on-line without sample preparation by (19)F/(1)H-HPLC-NMR spectroscopy. (19)F-HPLC-NMR spectroscopy was used in the continuous-flow mode, which enabled the HPLC chromatographic retention times (t(R)) of the metabolites to be established in a single analytical step. 3. In total, three (19)F-NMR signals could be detected, of which one was identified as the parent compound. Two earlier eluting metabolites were identified to be alpha- and beta-glucoside conjugates of 3-TFMA. 4. Metabolites at the lower (sublethal) exposure levels of 10, 1 and 0.1 micro g cm(-2) escaped identification by (19)F/(1)H-HPLC-NMR spectroscopy as outlined here and will require concentration prior to analysis.     

2-Chloro-3-pyridin-3-yl-5,6,7,8-tetrahydroindolizine-1-carboxamide (CMV423), a new lead compound for the treatment of human cytomegalovirus infections

Human cytomegalovirus (HCMV) remains one of the major pathogens in immunocompromised patients (AIDS and transplants) and the main cause for congenital infections leading from slight cognitive defects up to severe mental retardation. The drugs that are currently available for the treatment of HCMV infections, i.e. ganciclovir, foscarnet and cidofovir, are all acting at the level of the viral DNA polymerase. Here we describe an entirely new molecule, the 2-chloro-3-pyridin-3-yl-5,6,7,8-tetrahydroindolizine-1-carboxamide (CMV423), that shows very potent in vitro activity against HCMV. CMV423 is highly active against HCMV reference strains and clinical isolates, but also against those strains, isolated from patients or emerging after in vitro selection, that are resistant to either ganciclovir, foscarnet or cidofovir. CMV423 also showed activity in two ex vivo models, that are both highly relevant for the pathophysiology of HCMV, the retinal pigment epithelial and the bone marrow stromal cell assays. Viral antigen expression analysis by flow cytometry, as well as time of addition experiments, confirmed that CMV423 acts on a step of the viral replicative cycle that precedes the DNA polymerase step and, most likely, coincides with the immediate early (IE) antigen synthesis. Finally, CMV423 combined with either ganciclovir, foscarnet or cidofovir in checkerboard experiments demonstrated a highly synergistic activity.