Theoretical model of gastrointestinal absorption of lead.

A theoretical model is presented which is used to explain gastrointestinal absorption of ingested lead from use of traditional medicines. Dissolution processes are discussed and the relative contributions of pore and passive diffusion through the intestinal epithelium for the resulting species examined. The determination of the rate of absorption is described in terms of a mathematical three-compartment system and effects of particle size are considered by reference to the Noyes-Whitney dissolution rate law.

Compliance and drug therapy in fasting Moslem patients.

The effects of fasting on the drug regimens of 81 Asian Moslem patients during the religious month of Ramadan have been examined. Twenty-two male and 15 female patients were found to change their drug dosage pattern while fasting: 35 missed doses; 8 took their tablets at different times and 4 patients took all their medication as one single daily dose after breaking fast in the evening. The consequences of these changes are discussed and ways in which the problems which arise may be overcome are examined.

The clinical significance of metal binding in convulsion control with sodium valproate.

The facility with which certain metal salts of physiological importance can bind to the anticonvulsant drug, sodium valproate, is demonstrated. The products are characterized in vitro and the clinical significance of these findings are discussed in terms of the hair loss side-effect exhibited by some patients who are prescribed the drug for the treatment of epilepsy. The first reports are also given of preliminary in vivo data on the copper and zinc status of paediatric patients on sodium valproate.

Lead-induced convulsions in young infants--a case history and the role of GABA and sodium valproate in the pathogenesis and treatment.

A detailed case history of lead poisoning in a young infant is presented. Attention is directed towards the nature of the induced convulsions observed in such cases and the possible role of the GABAergic neuroinhibitory system. In vitro data demonstrating direct lead-GABA interaction is presented and sodium valproate, an effective anticonvulsant which affects GABA function, is shown to be an appropriate agent for medication in lead-induced convulsions. The hypothesis is presented that lead interacts with GABA which thereby reduces the neuroinhibition and that this may be counteracted by the action of sodium valproate.

Lead sulphide and traditional preparations: routes for ingestion, and solubility and reactions in gastric fluid.

Lead sulphide frequently occurs as a fallacious materia medica in traditional preparations used throughout the Moslem world. Although one of the least soluble lead compounds, use of this material as an eye powder has been directly associated with elevated blood-lead levels in children. Data are presented from animal studies which show the primary route for ingestion of the eye cosmetic is not transcorneal transport. Conversion of the sulphide to the more soluble (and hence more readily absorbed) chloride form is shown to occur in gastric fluid and, significantly, a marked dependence of the rate of dissolution on particle size is found. This may explain the disparity in previous reported values for the extent of absorption of ingested lead sulphide.

Whole-cell versus total RNA extraction for analysis of microbial community structure with 16S rRNA-targeted oligonucleotide probes in salt marsh sediments.

rRNA-targeted oligonucleotide probes have become powerful tools for describing microbial communities, but their use in sediments remains difficult. Here we describe a simple technique involving homogenization, detergents, and dispersants that allows the quantitative extraction of cells from formalin-preserved salt marsh sediments. Resulting cell extracts are amenable to membrane blotting and hybridization protocols. Using this procedure, the efficiency of cell extraction was high (95.7% +/- 3.7% [mean +/- standard deviation]) relative to direct DAPI (4',6'-diamidino-2-phenylindole) epifluorescence cell counts for a variety of salt marsh sediments. To test the hypothesis that cells were extracted without phylogenetic bias, the relative abundance (depth distribution) of five major divisions of the gram-negative mesophilic sulfate-reducing delta proteobacteria were determined in sediments maintained in a tidal mesocosm system. A suite of six 16S rRNA-targeted oligonucleotide probes were utilized. The apparent structure of sulfate-reducing bacteria communities determined from whole-cell and RNA extracts were consistent with each other (r(2) = 0.60), indicating that the whole-cell extraction and RNA extraction hybridization approaches for describing sediment microbial communities are equally robust. However, the variability associated with both methods was high and appeared to be a result of the natural heterogeneity of sediment microbial communities and methodological artifacts. The relative distribution of sulfate-reducing bacteria was similar to that observed in natural marsh systems, providing preliminary evidence that the mesocosm systems accurately simulate native marsh systems.

Fused aminotetralins: novel antagonists with high selectivity for the dopamine D3 receptor.

Starting from a series of 2-aminotetralins 1, a novel series of N-[4-(4-phenylbenzoylamino)butyl]-octahydrobenzoquinolines and hexahydrobenzoindoles with high potency and selectivity for the dopamine D3 receptor has been designed. The effect of ligand chirality on binding affinity has been established. Selected derivatives (e.g. 2o, 2p) show high functional selectivity and enhanced in vivo properties compared to 1.