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Biomedical subjects

C R Clark

Publications and source records attributed to C R Clark.

At least 217 records · Page 12Linked to original sources

BOMT (6 alpha-bromo-17 beta-hydroxy-17 alpha-methyl-4-oxa-5 alpha-androstan-3-one) is not an androgen antagonist within the central nervous system.

This study investigates the efficiency of BOMT as an androgen antagonist within the central nervous system. The efficiency of BOMT in suppressing neural receptor binding of testosterone, and the ability of this antiandrogen to block the feedback loop of testosterone onto the central nervous system, as evidenced by plasma testosterone levels, is reported. BOMT was found to be unable to open the feedback loop of testosterone onto the central nervous system, which was correlated with the low competing efficiency of this antiandrogen for receptor sites in vitro within the hypothalamic-preoptic area of the brain - a region known to be involved in gonadotrophin secretion. The observed divergence in the degree of antiandrogenicity of BOMT between peripheral and central target tissues of testosterone is discussed.

Androgen Antagonists↗

Identification of some benzodiazepines of forensic interest.

Ten benzodiazepines--clorazepate, nitrazepam, clonazepam, oxazepam, lorazepam, chlordiazepoxide, N-desmethyldiazepam, diazepam, prazepam, and flurazepam--in solid dosage form are identified by ultraviolet (UV) and infrared (IR) spectrophotometry and by high pressure liquid chromatography (HPLC). UV absorption data and IR spectra of the 10 benzodiazepines are provided and HPLC separation methods are described.

Benzodiazepines↗

Antipyrine plasma half-life. In vivo indicator of oxidative metabolic capability in Rhesus monkeys (Macaca mulatta).

Antipyrine plasma half-life (APH) has been used as an indicator of hepatic oxidase activity in rhesus monkeys (Macaca mulatta). Plasma disappearance of 14CH3-N-antipyrine (AP) was measured radiometrically. AP and 3 metabolites were detected using high pressure liquid chromatography. APH was assessed during a 300-day control period and following phenobarbital (PB) pretreatments. Significant interindividual variability was observed requiring that animals be used as their own controls. PB (15 mg/kg i.m., 2/day X 4 days) reduced mean APH values from 81 +/- 12 to 41 +/- 2 min. PB treatment also increased monooxygenase catalyzed aldrin epoxidation, dihydroisodrin hydroxylation and benzo(a)pyrene oxidation measured using liver biopsy homogenates. These parameters permit 'continual' assessment of HMO activity in rhesus monkeys under a variety of experimental conditions.

Animals↗

High speed liquid chromatography, 14C-radioassay and spectrophotometry for measuring antipyrine plasma half-life in rhesus monkeys (Macaca mulatta).

6 male rhesus monkeys (Macaca mulatta) were treated with 14CH3-N-antipyrine (15 mg/kg, i.v.). Antipyrine plasma half-lives (APH) were determined using HSLC, radiometric, and spectrophotometric methods. APHs obtained by HSLC analysis of plasma extracts were lower than radiometric and spectrophotometric determinations. The three procedures were investigated to determine if coextraction of metabolites might be responsible for differences in APH. All three solvent systems extract significant quantities of antipyrine metabolites. N-desmethylantipyrine and 3-hydroxymethylantipyrine may interfere with spectrophotometric determination of antipyrine. While all three methods are capable of detecting changes in hepatic oxidative metabolism, HSLC permits direct measurement of antipyrine concentrations and APH.

Animals↗

SKF 525-A inhibition of hepatic monooxygenase activity in rhesus monkeys.

Pretreatment of 3 male rhesus monkeys (Macaca mulatta) with SKF 525-A(20 mg/kg, i.m.) 3 h prior to to injecting 14CH3-N-antipyrine (30 mg/kg, i.v.) increased antipyrine plasma half-life (APH) 240--500%; measurements of APH made 4, 8 and 11 days after SKF 525-A treatment were also higher than control values. Increases correspond to decreased plasma levels of 3-hydroxymethylantipyrine and 4-hydroxyantipyrine and decreased rates of aldrin epoxidation in liver biopsy homogenates. Comparison of HSLC and radiometric methods for determining APH showed that both methods were capable of detecting chemically altered hepatic monooxygenase activity.

Aldrin↗

Kindergarten predictors of three aspects of reading achievement.

Kindergarten measures of intelligence, auditory perception, visual perception, and associative learning were used to predict three aspects of reading achievement (word attack, word recognition, and comprehension) at the end of Grades 1,2, and 3 for 79 subjects. The predictability of each measure was a function not only of grade, but also of the aspect of reading achievement being predicted. Multiple correlations of the predictors tended to increase across grade levels and were highest for the comprehension aspect of reading. The Number Facility subtest of the PMA was the over-all best predictor or reading achievement. Possible reasons for this and other findings are discussed.

Achievement↗

The effect of biopsy-hole shape and size on bone strength.

Investigation in cadaver femora of the relationship between the shape or size of a hole made in the cortex and the breaking strength of the bone revealed that of the shapes studied, an oblong hole with rounded ends afforded the greatest residual strength. Furthermore, we found that increasing the width of the hole caused a significant reduction in strength, while increasing the length did not.

Biopsy↗

Conformational aspects of the antifibrillatory activity of procaine.

The effects of procaine and four semi-rigid conformational analogs (compounds 1,2,3 and 4) were tested and compared on isolated rabbit atria. Procaine and the four analogs produced positive inotropic effects at all dose levels tested. The antifibrillatory activity of procaine and its analogs arranged in decreasing order of activity was compound 4 greater than 3 greater than 2 greater than 1 greater than procaine. The antifibrillatory activity of the compounds correlated to the distance between the ring nitrogen and the ester oxygen; that is, as the N-O distance increased the concentration required to reduce the following frequency decreased. However, the compound became more toxic as the N-O distance increased. Our data do not confirm the commonly regarded direct relationship between local anesthetic activity and antifibrillatory activity of procaine. Differences in activity displayed by the isomers of procaine could reflect differences in the ability of these analogs to bind to receptors responsible for the respective actions.

Animals↗

Effect of adrenalectomy and dexamethasone treatment on circadian running in the rat.

Although adrenalectomy resulted in a marked decrease in total wheel running activity in male rats, the circadian rhythm of the running was not altered. Contrary to what has been previously observed in animals with intact adrenal glands, administration of the synthetic glucocorticoid dexamethasone to adrenalectomized animals resulted in an immediate increase in the amount of running with no effect on the circadian distribution of running. It was concluded that the adrenal axis had an influence on an animal's ability to express running behavior, but the adrenal axis had no influence on the neural control of the circadian rhythm of running.

Adrenal Glands↗

2-Azabicyclo (2.2.2)octane analogues of the prodine analgetics.

The synthesis and analgetic activity of analogues of prodine-type analgetics in which the conformation of the piperidine ring is restricted in the boat form using the 2-azabicyclo (2.2.2)octane nucleus are reported. One of these analogues, 2-methyl-6-trans-phenyl-6-cis-propionoxy-2-azabicyclo (2.2.2)octane (3), showed significant analgetic activity (ED50 equals 3.1 mg/kg).

Alphaprodine↗