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Biomedical subjects

R V Smith

Publications and source records attributed to R V Smith.

At least 91 records · Page 5Linked to original sources
PubMed1979

N-demethylation of lergotrile by Streptomyces platensis.

Thirty-eight microorganisms were screened for their ability to produce metabolites of the semisynthetic alkaloid, lergotrile. A total of five microorganisms were found to biotransform lergotrile, and N-desmethyl lergotrile was detected as the principal metabolite with most organisms. Streptomyces platensis (NRRL 2364) appeared to form the metabolite in highest yield, and a preparative-scale conversion was accomplished with a recovered yield of 50%. Structure proof was accomplished with comparative thin-layer chromatography, mixed melting point, mass spectrometry, and remethylation to lergotrile.

Biotransformation↗
PubMed1979

Plasma levels of apomorphine following intravenous, intraperitoneal and oral administration to mice and rats.

Clinical use of the potent dopaminergic partial-agonist apomorphine (APO) in a wide variety of neuropsychiatric disorders is hampered by a lack of data concerning tissue/plasma levels following various routes of administration. In the present experiments, plasma levels were assessed at various times up to 4 hours after APO administration IV, IP, and PO to mice and rats. Plasma levels of total radioactivity after PO administration of [3H]-APO were 50 to 65% of those seen after IV administration, but brain levels were almost undetectable after PO administration. Organic solvent-extractable concentrations of tritium-labelled material after IV and IP administration of [3H]-APO to mice were significantly lower than the levels of total radioactivity, while after PO administration, these concentrations were minimal. Similar results were observed in rats following IV and PO administration of [3H]-APO.

Administration, Oral↗
PubMed1978

Primary monolayer cultures of postnatal rat liver cells with extended differentiated functions.

Monolayers of liver cells cultured from postnatal rats were grown in two types of media. One set of cultures was grown in selective medium which contained ornithine but was deficient in arginine; the other set was grown in nonselective medium which contained arginine but no ornithine. The cultures that were grown in the nonselective medium contained primarily a mixture of two cell types found in the liver: parenchymal hepatocytes and fibroblast-like cells. The fibroblast cells tended to overgrow the hepatocytes after several days in culture. In contrast, fibroblast overgrowth was inhibited in cultures grown in the selective, arginine-deficient medium, thereby resulting in relatively pure cultures of functional parenchymal hepatocytes. Comparative studies of sulfobromophthalein (BSP) uptake showed that the cultures grown in selective medium continued to be active much longer than the cultures grown in the nonselective medium. Pyruvate kinase assays revealed that the cultures grown in selective medium contained primarily the L-isoenzyme type which is characteristic of parenchymal hepatocytes. Cultures grown in nonselective medium contained a mixture of L- and M-isoenzymes which is indicative of nonparenchymal liver cells. The reported results indicate that selective, arginine-deficient medium permits primarily the growth of parenchymal hepatocytes found in neonatal rat liver.

Animals↗
PubMed1978

Regiospecific synthesis of isoapocodeine from 10,11-dimethoxyaporphine by using Cunninghamella elegans.

A preparative-scale regiospecific conversion of 10,11-dimethoxyaporphine to isoapocodeine was conducted with Cunninghamella elegans ATCC 9245. This biotransformation proceeded quantitatively in suspensions and was pH dependent. The influence of antioxidants on the conversion was studied. Attempts to preserve the activity of isolated C. elegans cells by a number of methods were unsuccessful.

Antioxidants↗
PubMed1978

Comparison of behavioral arousal induced by apomorphine and N-n-propylnorapomorphine.

A preliminary evaluation of behavioral arousal in mice, as a model system for quantifying activity of presumptive antiparkinsonian and antischizophrenic agents, was made. In experiments not yet published, we have observed stereotypic cage climbing induced by two aporphines (apomorphine, APO; and N-n-propylnoraporphine, NPA) to be specifically dopaminergic. Time of peak effect was found to be 15--30 min and an ED50 of approximately 4 mg/kg was established for both drugs. In the present study we have investigated the activity of APO and NPA on behavioral arousal. As measured by electromagnetic sensors, behavioral arousal reflects several responses including spontaneous locomotor activity and repetitive movements (e.g., grooming and rearing). The procedures which we have employed minimize artifacts due to handling and injection routines while maximizing our ability to observe time of peak effect (based on blood levels). Dose and time response analyses of APO and NPA (i.p.) demonstrated a time of peak effect from 15--30 min and ED50 values of 3.0 and 2.5 mg/kg for APO and NPA, respectively. The results of our experiments show that for a 90 min period over the 1--10 mg/kg dose range employed, APO exhibits a linear dose response relationship whereas that for NPA is sigmoidal. Similarities in time of peak effect and ED50s for the two aporphines in stereotypic cage-climbing and behavioral arousal experiments suggest that the behavioral arousal induced by APO and NPA may be dopaminergically mediated.

Animals↗
PubMed1977

Gas chromatographic determination of apomorphine in plasma.

A method is described for the analysis of 1 to 10 microgram/ml concentrations of apomorphine in plasma. The procedure is based on ethyl acetate extraction, a back extraction cleanup-step, derivatization with heptafluorobutyric anhydride, and gas chromatography on a 3% OV-17 column using flame ionization detection. N-n-Propylnorapomorphine is employed as an internal standard and quantitative relative recoveries of drug are realized with relative standard deviations of 4.6%. The method permits analysis of apomorphine in the presence of its two monomethyl ether metabolites, apocodeine and isoapocodeine. The latter compounds are also chromatographically resolved as their heptofluorobutyrate derivatives.

Apomorphine↗
PubMed1977

GLC determination of indoprofen in plasma.

Implementation of human bioavailability studies with the analgesic indoprofen required a rapid, sensitive, and convenient assay in blood plasma. A procedure based on ether extraction of acidified plasma, derivatization with diazomethane, and GLC analysis using a 3% OV-1 column was sufficiently sensitive for measurement of plasma indoprofen concentrations in the 0.4-16 mug/ml range. An average recovery of 99.0 +/- 7.6% (SD) was achieved when the pentanoic acid homolog was employed as an internal standard.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1976

NMR study of amphetamines using europium shift reagents.

Amphetamine and certain of its methoxylated derivatives show a high degree of interaction with NMR shift reagents of the type tris (1,1,1,2,2,3,3-heptafluoro-7,7-dimethyl-4,6-octanedione)europium(III). The shifts are not accompanied by appreciable line broadening, and both the aliphatic and aromatic protons can be resolved. The strong interaction between amine and shift reagent diminishes rapidly as the amine function is alkylated. For derivatives containing ortho-methoxyl groups, a weaker interaction with this functionality also becomes evident as the amine is alkylated. The stereospecificity of the shifting process was investigated by employing tris[3-(trifluoroacetyl)-d-camphorato]europium(III), a chiral shift reagent, with stereochemically pure enantiomers and known enantiomeric mixtures. Although certain (R)-enantiomers showed greater downfield C-methyl groups shifts, these shift differences from the corresponding (S)-enantiomers were small and not well resolved.

Amphetamines↗
PubMed1976

Spectrofluorometric determination of hydroflumethiazide in plasma and urine.

A rapid, accurate, sensitive, and reproducible assay for hydroflumethiazide in plasma and urine was developed after studies of its UV and fluorescence spectral properties and partitioning behavior. The assay is based on initial extraction from acidified plasma or urine into ether, back-extraction into basic solution followed by acidification to about pH 1, and measurement of the fluorescence derived from the unionized molecule. Analysis of variance indicated no significant differences in assays performed on the same day. The mean recovery was 98.8 +/- 7.4% for plasma over a concentration range of 0.2-2.0 mug/ml. The method is convenient for routine clinical use and has sufficient sensitivity to quantify hydroflumethiazide levels after administration of therapeutic doses.

Animals↗
PubMed1976

Congenital megalourethra associated with prune belly syndrome.

Dilation of the penile urethra is described in a male infant with the classic triad of the prune belly syndrome. This dilated penile urethra was not accompanied by obstruction of the urethra proximal or distal to the dilation. Dilation of the penile urethra is a rare feature of the prune belly syndrome and may be part of the same developmental abnormality that affects the remainder of the urinary collecting system.

Abdominal Muscles↗