PubMed Health⌕ Search

Biomedical subjects

R Brodie

Publications and source records attributed to R Brodie.

6 recordsLinked to original sources

Development and validation of a bioanalytical method for the determination of the cholecystokinin type-1 (CCK(1)) receptor antagonist dexloxiglumide in human plasma.

A sensitive bioanalytical method for the measurement of dexloxiglumide, a new selective and potent cholecystokinin type-1 (CCK(1)) receptor antagonist, in plasma, is reported. The method is based on reversed-phase liquid chromatography with ultraviolet absorption detection. Samples are extracted under acidic conditions into an organic solvent, and following evaporation, reconstitution and centrifugation stages, the supernatant is injected on to an ODS column with detection at 244 nm. The method has been validated over the concentration range 0.2-20 microgram/ml, 0.2 microgram/ml being the lower limit of quantification. The overall precision and accuracy (expressed as relative error) of the method was less than 6.1 and 2.3%, respectively. Dexloxigulmide was shown to be stable in plasma when stored at -20 degrees C for at least 200 days. The method is suitable for studying the pharmacokinetics of dexloxiglumide in man.

Calibration↗

Retinoid hepatitis.

A 65-year-old woman treated with etretinate for pityriasis rubra pilaris developed chronic active hepatitis. The elevated transaminases were noted 2 months after initiation of therapy and peaked 2 months after discontinuation of etretinate. The spectrum of liver toxicity induced by etretinate is reviewed. We suggest that reported cases of retinoid-induced liver disease can be divided into four distinct categories: nonspecific reactive hepatitis, acute hepatitis, chronic active hepatitis, and severe fibrosis or cirrhosis.

Aged↗

Further characterization of the neurofunctional effects of the calcium ionophore A23187.

Calimycin (A23187), a divalent cationic ionophore which increases intraneuronal concentrations of calcium, has been shown to produce neurofunctional changes associated with depression of brain excitability. The present report describes further characterization of the neurofunctional effects of acute parenteral exposure to A23187. Adult male rats were tested for the effects of A23187 on operant performance and general motor activity. In order to gain some insight into the neuronal systems which may be affected by A23187, brain levels of norepinephrine (NE), dopamine, serotonin, and their metabolites were determined. In addition, provocative pharmacologic challenges were employed to assess the interaction between A23187 and the centrally active drugs amphetamine (AMPH), scopolamine (SCOP), or chlorpromazine (CPZ). A23187 was found to effectively suppress fixed ratio-15 operant performance (p less than 0.001) at a dose of 0.5 mg/kg. This effect was temporary in nature inasmuch as performance was normalized by the day after dosing. This same dose of A23187, which produces a selective hypomotility, was found to have no apparent latent effects on the processes controlling circadian motor activity. Neurochemically, A23187 at 1 mg/kg induced a 64% increase (p less than 0.01) in the NE metabolite 3-methoxy-4-hydroxyphenylglycol, although levels of NE were unaffected. In the pharmacological challenge studies, AMPH and SCOP both attenuated and CPZ enhanced the acute hypomotility induced by 0.5 mg A23187/kg. The data show that low doses of A23187 induce a specific pattern of neurobehavioral dysfunction which may involve some interaction between the central catecholaminergic and cholinergic systems.

Animals↗

Glucose transport and metabolism in cultured human skin fibroblasts.

Human skin fibroblast cultures, seeded at 10(5) cells/5 cm plate and allowed to grow to confluence at approx. 10(6) cells/5 cm plate, utilized a glycolytic mode of metabolism where the ratio of glucose utilized to lactate produced wa 0.62 +/- 0.05 (Zielke, R.H., Ozand, P.T., Tyldon, J.I., Sevdalian, D.A. and Cornblath, M. (1976) Proc. Natl. Acad. Sci. U.S.A. 73, 4110-4114) (mean +/- S.E.). When the glucose in the medium was exhausted, the lactate produced during the highly glycolytic phase was then reutilized. In monolayer cultures that had been washed with phosphate-buffered saline, rates of glucose utilization were measured at 0.25 and 2 mM glucose by monitoring the appearance of 3H2O from [5-3H]glucose. Rate of utilization for each concentration of glucose decreased markedly as the cultures became more confluent. This decrease also correlated with a reduced ability to transport glucose as measured by 2-deoxy-[3H]glucose uptake in washed monolayer cultures. In washed confluent culture of fibroblasts, glucose utilization was markedly decreased by the presence of pyruvate and lactate but not by glutamine. The respiratory inhibitors, rotenone and antimycin, did not increase the rate of glucose utilization except when added in combination with pyruvate. We conclude that cultured skin fibroblasts possess a highly glycolytic mode of metabolism but that this mode can become more oxidative in the presence of sufficient quantities of pyruvate and lactate.

Biological Transport↗