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Biomedical subjects

S Slater

Publications and source records attributed to S Slater.

At least 55 records · Page 3Linked to original sources

In vitro and in vivo effects of ribavirin on human respiratory epithelium.

The effects of ribavirin, a broad spectrum antiviral agent, on the structure and function of normal human nasal epithelium have been studied in vitro, as has also the in vivo effect of treatment with nebulised ribavirin on nasal mucociliary clearance of saccharin in four patients. Ciliary beat frequency was measured by a photometric technique, and changes in epithelial and ciliary ultrastructure were assessed by transmission electron microscopy. Ribavirin solution at the recommended concentration of 20 mg/ml had no adverse effects on ciliary activity in vitro; at concentrations of 50 mg/ml and above it slowed ciliary beating significantly and at 60 mg/ml caused ciliostasis associated with epithelial disruption. Nasal inhalation of ribavirin at 60 mg/ml for up to 20 minutes, however, did not slow nasal mucociliary clearance, nor did it adversely affect the ciliary beating or structure of nasal ciliated epithelium examined in vitro immediately after inhalation.

Aged↗

Paracetamol analysis: evaluation of a new kit for enzymatic assay.

Paracetamol in serum was assayed by a new enzymatic method, and the results compared with a high performance liquid chromatographic method. Results by the two procedures agreed well (t = 0.05). The correlation coefficient was 0.999, and the slope and intercept by Deming analysis were 0.975 and 0.003 mmol/l respectively. The enzymatic method represents a simple, accurate, precise and not too costly method with several advantages over many currently used techniques. It is eminently suitable for the smaller laboratory, and for use out of normal hours.

Acetaminophen↗

Diabetic ketoalkalosis: a complex mixed acid-base disorder.

A mixed acid-base disturbance in a long-standing insulin dependent diabetic resulting in a combination of hyperglycaemic ketosis with an alkalosis is reported, in which an analysis of the biochemical mechanisms involved helped to clarify the clinical problem.

Adult↗

The effects of various substituted hydrocarbons on two heme synthesis regulatory enzymes.

Benzene and some of its derivatives have been shown to cause alterations in heme and globin synthesis. Structure/activity relationships of the effects of substituted aromatic hydrocarbons on delta-aminolevulinic acid synthetase (ALAS) and ferrochelatase (FC) activities were studied. These enzyme systems were studied because they were regulatory and represented the initial and final enzymes in the biosynthesis of heme. Normal values for rat liver ALAS were 250-350 microM ALA/g protein/30 min, mean 293 microM/g +/- 44 (SD). Normal values for FC were 12-40 microM heme/g protein/45 min, mean 18 microM/g +/- 0.7 (SD). Nitrosonaphtholics inhibited ALAS activity an average of 49%; nitrosobenzenes, 48%; chloronitrobenzoic acids, 39%; phenol, 37%; nitrophenols, 22%; aminophenols, 16% and chlorophenols, 5%. Certain compounds inhibited FC activity: nitrosonaphtholics, 99%; chlorophenols, 56% and nitrosobenzenes, 3%. Some compounds that significantly inhibited ALAS activity enhanced FC activity, e.g. phenolic compounds and chloronitrobenzoic acids. The inhibitory effect may reflect a blockage of the active site of the enzymes and/or binding of a required substrate. The enhancing effect may be due to making the binding site of the heme pocket of the porphyrin more accessible to iron. These techniques may prove useful for assessing toxicity of pollutants in animal species.

5-Aminolevulinate Synthetase↗

Plasma prolactin changes following fenfluramine in depressed patients compared to controls: an evaluation of central serotonergic responsivity in depression.

In an attempt to evaluate the responsiveness of the serotonergic neurotransmitter system in depression, fenfluramine, a serotonin releasing agent, was administered to 18 depressed patients and 10 controls, and placebo was administered to 16 of the depressed patients in a double-blind paradigm. Plasma prolactin levels were measured prior to and for five hours following fenfluramine. Fenfluramine produced a significant increase in prolactin in both patients and controls. However, the prolactin response to fenfluramine whether measured as an absolute increase or percent increase from baseline was significantly less in depressed patients than controls. This difference remained equally statistically significant when age-and-sex-matched pairs of depressed patients and controls were compared. These results suggest that the central serotonergic system is less responsive in depressed patients than controls.

Adult↗

High plasma norepinephrine levels in patients with major affective disorder.

The authors found that patients with major affective disorder had higher levels of plasma norepinephrine and higher pulse rates (tachycardia) than healthy control subjects, but their blood pressures were normal. These measurements were similar in all three subgroups of patients with affective disorder--manic, bipolar depressed, and unipolar. Because norepinephrine is the primary neurotransmitter of the sympathetic nervous system, these data suggest sympathetic hyperactivity in the major affective disorders. This conclusion is compatible with recent speculation based on the effect of antidepressants on noradrenergic receptors and a failure of alpha-receptors to downregulate normally in patients with major affective disorder.

Adult↗

Improved radiochemical method for measuring ferrochelatase activity.

We describe a radiochemical method for measuring ferrochelatase activity in the in vitro incorporation of iron into mesoporphyrin-IX to form mesoheme. 59Fe is used to quantify ferrochelatase activity in rat liver. The uptake of iron is linearly related to the time allowed for it to occur, and the reaction proceeds optimally under reducing and anerobic conditions, maintained in sealed lyophilization vials under a positive pressure of nitrogen.

Animals↗

The effect of growth hormone administration on human sleep: a dose-response study.

Human growth hormone and saline were administered for one night each to normal volunteers in a cross-over study. A dose of 2 units im given 15 min before bedtime had no effect on sleep EEG parameters. In contrast, 5 units resulted in a 19% decrease in slow-wave sleep (p < 0.01) and a 13% increase in REM sleep (p < 0.05). Neither doe, when given during daytime, affected tests of affect or serial learning.

Adolescent↗

Comparative behavioral effects of clorgyline and pargyline in man: a preliminary evaluation.

The antidepressant and other behavioral effects of clorgyline, a preferential inhibitor of monoamine oxidase (MAO) type A, were compared with those of pargyline, a preferential inhibitor of MAO type B, in 16 depressed patients. In a subgroup of more severely depressed patients, clorgyline treatment for 4 weeks resulted in significant improvement on both observer-rated and self-rated scales, while minimal changes occurred during pargyline treatment. Similarly, in a crossover study that included 8 patients examined with multiple scales, clorgyline had generally greater antidepressant and antianxiety effects than did pargyline, although pargyline had some activating effects and also tended to produce more side effects. MAO type A inhibition may be more important than MAO type B inhibition for antidepressant efficacy.

Clinical Trials as Topic↗

Selectivity of clorgyline and pargyline as inhibitors of monoamine oxidases A and B in vivo in man.

During 4 weeks of treatment with clorgyline, a selective MAO-A inhibitor, platelet monoamine oxidase (MAO) activity was unchanged. During a similar 4-week crossover treatment period with pargyline, a selective MAO-B inhibitor, platelet MAO activity was essentially completely inhibited in the same individuals. The differential effects of the two drugs on platelet MAO, which consists exclusively of the MAO-B form, suggests that the in vitro selectivity of clorgyline, and possibly of pargyline, on MAO-A and MAO-B may be maintained in vivo during long-term administration in man. Reductions in blood pressure, heart rate, and plasma amine oxidase activity were generally similar in magnitude during treatment with both drugs, however, suggesting that either these effects are nonspecific consequences of both MAO-A and MAO-B inhibition, or that pargyline also inhibited MAO-A activity.

Blood Platelets↗