[Import of tropical human cutaneous myiases].
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Biomedical subjects
Publications and source records attributed to M Leclercq.
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Vitamin K status was evaluated using coagulation studies and/or vitamin K1 assays in a total of 53 normal fetuses and 47 neonates. Second trimester fetal blood samples were obtained for prenatal diagnosis under ultrasound guidance. Endogenous vitamin K1 concentrations (determined by high performance liquid chromatography) were substantially lower than maternal levels. The mean maternal-fetal gradient was 14-fold at mid trimester and 18-fold at birth. Despite low vitamin K levels, descarboxy prothrombin, detected by a staphylocoagulase assay, was elevated in only a single fetus and a single neonate. After maternal oral supplementation with vitamin K1, cord vitamin K1 levels were boosted 30-fold at mid trimester and 60-fold at term, demonstrating placental transfer. However, these levels were substantially lower than corresponding supplemented maternal levels. Despite elevated vitamin K1 concentrations, supplemented fetuses and neonates showed no increase in total or coagulant prothrombin activity. These results suggest that the low prothrombin levels found during intrauterine life are not due to vitamin K deficiency.
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Macrolide antibiotics are concentrated by phagocytic cells in vitro. We studied the in-vivo uptake of josamycin by alveolar macrophages recovered by broncho alveolar lavage performed in patients 3 h after ingestion of 1 g of the drug. Simultaneous determination of the antibiotic levels was performed on the BAL supernatant and the serum and the results compared to those obtained by incubating alveolar macrophages and blood polymorphonuclears at 2 and 8 mg/l. Josamycin concentration was measured using a high pressure liquid chromatography method. Results show that intracellular josamycin levels in vivo are similar to those observed in vitro. Accumulation of the drug also occurs in BAL fluid (reaching about a 100-fold the serum concentration). Pulmonary and serum levels are significantly correlated.
The in-vitro and in-vivo uptake of spiramycin by human and animal alveolar macrophages was studied. In-vitro penetration was studied in guinea pig and human alveolar macrophages incubated in medium 199 at 37 degrees C containing spiramycin at various concentrations. Results were expressed as the cellular/extracellular concentration ratio (C/E). The in-vivo study was performed in patients receiving 500 or 1000 mg spiramycin every 8 h as a 1-h infusion on day 1. A single infusion was given on day 2, 2 h before serum and bronchoalveolar lavage (BAL) sampling. Spiramycin was assayed by HPLC, and by a microbiological assay. In guinea pig alveolar macrophages, the C/E ratio of spiramycin after 60 min at 37 degrees C was 20.3 +/- 6.5 when the concentration was 10 mg/l. In human alveolar macrophages, the C/E ratio was 21.3 +/- 8.7 at 5 mg/l spiramycin and 23.8 +/- 8.7 at 50 mg/l. The accumulated spiramycin was slowly released when the cells (guinea pig alveolar macrophages) were washed and re-incubated in antibiotic free medium. Spiramycin was able to penetrate the alveolar space. In BAL supernatant, spiramycin levels were about 24-fold the serum level (n = 6 patients), when the BAL/serum glucose ratios were used as the dilution estimate. Alveolar macrophage levels ranged from 17 to 210 mg/l (n = 6 patients receiving 500 mg spiramycin infusion). These results are consistent with the in-vitro data.
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The des-gamma-carboxyprothrombin (DCP) level was found to be increased in the majority of hepatocellular carcinomas (HCC). This increase has to be distinguished from an increased DCP level linked to a vitamin K deficiency. We studied the evolution of increased DCP level in 6 patients with histologically proven HCC and in 10 without HCC after slow injection of 20 mg of vitamin K1. The DCP assays performed subsequent to the vitamin K1 injection showed: first, a durable normalisation of the DCP level in the patients without HCC, suggesting that the increased DCP was linked, in them, to an underlying vitamin K deficiency; second, a transitory decrease followed by a return to the abnormal level in the patients with HCC. We can conclude that an increased DCP level which persists following vitamin K1 injection is specific for HCC. The minimal delay for the DCP assay after vitamin K1 injection seems to be 15 days.
Two series of 2-substituted 1,2-epoxyethanesulfonamides 2 and ethynesulfonamides 5 were synthesized and evaluated for their antifilarial activity. The trans epoxides 2T were stereospecifically prepared by a Darzens reaction between aldehydes and halomethanesulfonamides. The cis isomers 2c were obtained from ethynesulfonamides 5 by semihydrogenation followed by KOCl epoxidation. 2-Substituted ethynesulfonamides 5 were synthesized from appropriate trans-ethenesulfonamides by a bromination/dehydrobromination sequence. These products, as well as several synthetic intermediates, were evaluated for antifilarial activity against Molinema dessetae either in vivo in its natural host, the rodent Proechimys oris, or in vitro by a new test using cultures of the infective larvae. Most of the epoxides 2T and acetylenic derivatives 5 bearing a 2-aryl substituent were active in vitro. Among these compounds, four epoxides 2T and one acetylenic derivative 5 showed marked macrofilaricidal activity in vivo without any microfilaricidal activity. The differences between the in vivo and in vitro results may be due, in part, to the low chemical stability of the epoxy sulfonamides 2T. Despite this limitation, the activities observed in this reliable animal model suggest further development and testing of both series 2T and 5 as macrofilaricides.
An improved high-performance liquid chromatographic method was used to measure phylloquinone concentrations in human and cow's milk. Concentrations in human milk obtained serially from 10 mothers 3, 8, and 21 days after delivery were found to increase during the course of lactation. No correlation was found between phylloquinone concentration and lipids but a significant negative correlation was observed between phylloquinone and cholesterol concentrations. Determinations in cow's milk showed increased levels during the summer months. Also, levels in cow's milk were significantly higher than in human milk. Notwithstanding marked individual variations in human milk, phylloquinone concentrations in cow's milk always proved higher than in human milk. Results prompt the necessity of protecting breast-fed infants by applying relevant prophylactics measures.
Cow's milk has been shown to contain a protein complex which is able to bind vitamin K1 in a reversible manner. This binding property has been investigated by the celite method which consists in creating a dynamic equilibrium between the adsorbent, the celite and the protein complex for the ligand (vitamin K1). Based on competition experiment, the binding is specific and the vitamin K1 binding protein complex has a molecular weight equal to or higher than 7.5 X 10(2) KD.