Absorption and distribution of sodium [2-14C]barbital in tissues of normal and dystrophic mice.

The absorption and distribution of [2-14C]barbital after oral administration was studied in various tissues, including skeletal muscle, of normal and dystrophic mice. There appeared to be a more rapid gastric emptying in the mutant homozygote as reflected in lower levels of the drug recuperated from the gastrointestinal tract. This resulted in initially higher plasma and tissue concentrations of barbital in the dystrophic mice. Two hours after oral administration, this kinetic profile was reversed so that less barbital remained in the tissues of the dystrophic mouse. The tissue:plasma concentration ratios were consistently, but not significantly, higher in all tissues of the dystrophic animals. Analysis of the half-life of the drug in both groups suggests that there is an increase in the distribution volume of barbital in the dystrophic mice. The phenomenon of more rapid absorption of the barbiturate seems to be more consistent as the symptoms of the disease progress. The altered absorption and disposition of barbital in various tissues of the dystrophic mouse support the concept that a generalized multisystemic disorder may be crucial to the pathogenesis of murine muscular dystrophy, in contradistinction to a purely myogenic origin.

Cytochemical localization of glucose-6-phosphatase activity in the central nervous system of the rat.

The histochemical detection of glucose-6-phosphatase (G-6-Pase) in neurons of the CNS has been confirmed at the level of electron microscope. Both glucose-6-phosphate (G-6-P) and alpha-glycerophosphate (alpha-gP) can be used as substrates to localize the reaction product of this enzyme, which we have found in all cell types of the cerebral cortex, cerebellum and brain stem. The reaction was most prominent in large neurons, such as the Purkinje cells of the cerebellum and the pyramidal cells of the cerebral cortex. This is due to their extensive content of rough and smooth endoplasmic reticulum, the ultrastructural sites of G-6-Pase activity. It was possible to measure quantitatively the hydrolysis of G-6-P and alpha-gP in brain homogenates and also in microsomal fractions, the biochemical correlate of the cytochemically demonstrable activity. These results call for a reappraisal of the previous biochemical evidence, which negates the existence of brain G-6-Pase, and consequently a reassessment of current concepts pertaining to the metabolic regulation of brain glucose.

Short term hypothermic perfusion for intestinal preservation with dimethyl sulfoxide.

Morphologic changes, resulting from intracellular or extracellular perfusates with dimethyl sulfoxide as a cryophylactic agent, are similar and probably due to the anoxic period, after short term perfusion. These changes are temporary and are followed by complete recovery. No statistically significant changes in disaccharidase activity between intracellular and extracellular perfusates are found in the jejunal mucosa. No differences are found between normal disaccharidase activity and values obtained experimentally. Results of this study support the suggestion that vascular endothelial damage, as observed in evaluations utilizing the electron microscope, is certainly an important factor in the limitation of perfusion techniques of the intestine.

Scanning electron microscopy of surface irregularities and thrombogenesis of polyurethane and polyethylene coronary catheters.

Following routine coronary arteriography, surface irregularities and thrombogenesis of the inner and outer wall of six Ducor polyurethane and six RPX polyethylene coronary catheters were studied by scanning electron microscopy. Polyurethane catheters had rough and highly irregular external and internal surfaces. All catheters showed adherent thrombi on their external surface. The internal surface of three catheters showed evidence of thrombosis. Polyethylene differed from polyurethane in several respects. Although the external surface had an irregular and wavelike appearance, the internal surface was smooth and regular. Two polyethylene catheters showed thrombi on their external surface. The internal surface of one catheter showed single platelets in one area. These results confirm recent reports showing that internal and external surface irregularities play a major role in the initiation of thrombosis in and on intravascular catheters. They stress the need for high quality catheter materials with smooth and regular surfaces in the prevention of thromboembolic complications from coronary arteriography.

Cytochemical detection of nucleoside diphosphatase activity in the central nervous system of the rat.

The cytochemical localization of nucleoside diphosphatase and thiamine pyrophosphatase occurs within the "mature face" of the Golgi apparatus and over the neurilemma in neurons of the cerebellum, the cerebral cortex and the brain stem. The hydrolytic reaction product of the brain enzyme differs from that of the liver in that it is not found in the endoplasmic reticulum or nuclear envelope. Hydrolysis of IDP, UDP or GDP is not greater than that of ADP or CDP in brain homogenates, in contrast to that found in the liver. The NDPase activity of brain homogenates is optimal at pH 7.2, stimulated by heavy metals and inhibited by uranyl nitrate. Thick section cytochemistry suggests that the reaction product is restricted to a network of polygonally shaped compartments. NDPase activity on the neurilemma may reflect the role of this enzyme in the synthesis of glycoproteins involved in neuronal surface recognition.