Pulmonary absorption rate and bioavailability of drugs in vivo in rats: structure-absorption relationships and physicochemical profiling of inhaled drugs.

The aim of this investigation was to analyze the structure-absorption relationships for pulmonary delivered drugs. First, the inhaled drugs on the market during 2001 were identified and a profile of the calculated physicochemical properties was made. Second, an in vivo pharmacokinetic investigation was performed in anesthetized rats.

Histopathological and hemodynamic studies supporting hypoxia and vascular disruption as explanation to phenytoin teratogenicity.

The limb plates and craniofacial regions in rabbit fetuses were examined shortly after the last dose of phenytoin on day 16 after daily administration by gavage with either 150 mg/kg on days 14-16 or 300 mg/kg on days 15-16. Both treatment regimens resulted in similar changes. Histologically, the digital areas of the limb plates showed extensive edema and dilated blood vessels within 2 h.

Mutagenicity testing of condensates of smoke from titanium dioxide/hexachloroethane and zinc/hexachloroethane pyrotechnic mixtures.

Condensates of smoke from titanium dioxide/hexachloroethane and zinc/hexachloroethane pyrotechnic mixtures were investigated for their potential to produce genetic damage in the tester strains TA98, TA100, TA1535 and TA1537 of Salmonella typhimurium and in the mouse bone marrow micronucleus assay. Both smoke condensates contained several chlorinated hydrocarbons among which tetrachloroethylene, hexachloroethane, hexachlorobutadiene and hexachlorobenzene were identified by GC/MS. Condensate of smoke from titanium dioxide/hexachloroethane showed a dose-related positive response in the Salmonella assay with strains TA98 and TA100 in the absence of metabolic activation from rat liver S9 fraction.

Organophosphorus anticholinesterases do not mediate analgesia through inhibition of enkephalin degradation.

The effect on enkephalin degradation of the four highly potent organophosphorus anticholinesterases, soman, sarin, tabun and DFP was studied in synaptosomal fractions of rat brain striata. None of the agents effected any of the enkephalin degrading enzymes, the puromycin sensitive aminopeptidase, the p-hydroxymercurybenzoate (p-HMB) sensitive dipeptidyl aminopeptidase or the phosphoramidon sensitive enkephalinase. Furthermore, no peptidase function of acetylcholinesterase was found, when Leu-enkephalin was used as substrate at low concentrations (27 nM).

Effects of mercuric chloride on the membrane integrity of cultured cell lines.

The effects of mercuric chloride on the membrane integrity of neuronal (N1E115), glial (138MG), muscle (L6) and liver (BRL123) cells in culture were studied. Alterations in passive membrane permeability were investigated in a perfusion system by following the efflux of radioactivity from cells preloaded with tritiated 2-deoxy-D-glucose. The efflux increased rapidly in the presence of a low concentration of HgCl2 (10(-5) M).