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Biomedical subjects

M Franklin

Publications and source records attributed to M Franklin.

At least 109 records · Page 6Linked to original sources

The effect of diazepam on indices of 5-HT function in man.

The effects of acute and chronic diazepam administration on L-tryptophan induced prolactin release was studied in seven male volunteers. Acute diazepam diminished the prolactin neuroendocrine response to L-tryptophan. On chronic administration this effect was lost, suggesting tolerance had developed. The sedative effects of L-tryptophan were unaltered by either acute or chronic diazepam administration. A possible explanation for the tolerance development to the neuroendocrine effects may be the observed reduction in platelet 3H-imipramine binding that was observed.

Adult↗

Correlations between predominant heterotrophic bacteria and physicochemical water quality parameters in two canadian rivers.

The heterotrophic bacterial populations in two contrasting rivers have been examined over a period of 1 year. The populations were analyzed (i) as total heterotrophic counts, (ii) as species numbers, using numerical taxonomy, (iii) by diversity indices, and (iv) by factor analysis. Isolates were obtained by plating directly from water samples and by chemostat enrichment. Four factors emerged which profiled the bacterial community and were common to both rivers. They were, in order of decreasing importance, fermentative metabolism, inorganic nitrogen metabolism, fluorescence-oxidative metabolism, and lack of starch hydrolysis. Several factors produced significant correlations with a range of physicochemical parameters, which were also measured. The correlations suggested an intricate algal-bacterial interaction. The oxidative metabolism factor correlated with rainfall in one river, suggesting that the oxidative bacteria may be washed in from the surrounding land. In the other river, the oxidative-fermentative factor correlated negatively with sunshine. Factor analysis was the most effective method for revealing correlations between bacterial characteristics and the environmental parameters; however, the use of a variety of methods provided more insight into the ecological aspects.

Journal Article↗

Seasonal fluctuations in river bacteria as measured by multivariate statistical analysis of continuous cultures.

Forty-eight continuous culture enrichments were performed on summer and winter water samples from two contrasting rivers. The cell output from each chemostat was dependent on the temperature and nitrogen concentration of each enrichment. The diversity of the populations from the continuous cultures, as assessed by species diversity analysis, was always greater than populations obtained on agar plates. However, the species isolated exclusively by continuous culture in these experiments were not unique to the chemostat. All of these species had been isolated at some time on plates directly. High nitrogen concentrations were found to decrease diversity. Populations sampled during the winter were influenced primarily by the concentration of nitrogen. Summer isolates were affected mainly by the temperature of the culture medium. The nutritional versatility of the population was not affected by enrichment of the continuous culture.

Analysis of Variance↗

Neuroendocrine tests during treatment with neuroleptic drugs: I. Plasma prolactin response to chlorpromazine challenge.

Chlorpromazine (CPZ) 50 mg IM was administered to 21 schizophrenics receiving neuroleptic treatment. A further increase in plasma prolactin (PRL) was provoked in 8 subjects who had lower daily doses of neuroleptics than the remainder. The difference in the baseline PRL concentrations between the subgroups was inconsistent. In some patients, the test dose produced no change in plasma PRL but a further PRL rise was induced by raising the challenge dose or by an increase in the daily dose of neuroleptics. It is concluded that the PRL rise following CPZ 50 mg IM identifies some patients whose PRL response to the current treatment was only submaximal but the absence of PRL increment after this test dose is not sufficient evidence that the baseline level was already maximal.

Adult↗

Neuroendocrine tests during treatment with neuroleptic drugs I. Plasma prolactin response to haloperidol challenge.

The plasma prolactin (PRL) response to haloperidol 2 or 4 mg i.m. was studied in 18 schizophrenic men during their routine treatment with neuroleptic drugs. A substantial rise of the PRL level above the treatment baseline occurred in all but four of the 20 tests showing that the PRL elevation induced by treatment was not maximal. The challenge was ineffective only in patients receiving very high daily doses of medication. The increment was inversely correlated to the daily dose of medication but unrelated to plasma haloperidol concentrations during the test. Chronic schizophrenics who were receiving long term treatment and had low basal PRL levels did not show tolerance to the prolactin stimulating effect of haloperidol. That prolactin rose during the test in patients who had improved during their current treatment indicates that the degree of dopamine receptor blockade required for therapeutic effects is below that which produces a maximal PRL response.

Adult↗

Plasma fluphenazine and prolactin levels in schizophrenic patients during treatment with low and high doses of fluphenazine enanthate.

The relationship between plasma prolactin (PRL) and drug levels in patients receiving neuroleptic drugs is of special interest in view of evidence that the PRL elevation induced by these drugs reaches its maximum at sub-therapeutic doses. Plasma PRL and fluphenazine (FPZ) levels were measured by radioimmunoassay (RIA) in each of 11 chronic schizophrenics (nine men, two women) during two 4-week periods of treatment with FPZ enanthate at a "High Dose' (250 mg per week) and a "Low Dose' (12.5 mg per week) given in random order. Plasma PRL levels were above normal in 9 of 11 subjects during the last week of Low Dosage. High Dosage resulted in PRL levels significantly greater than found during Low Dose treatment in 9 of 11 patients. Thus the PRL response had not reached its "ceiling" during Low Dosage in most patients. A significant correlation between PRL and FPZ levels was found in seven subjects; evidence that immunoreactive FPZ levels relate to an effect caused by blockade of dopamine receptors. The plasma FPZ pattern between injections during week 1 of Low Dosage was remarkably stable; High Doses produced an initial drug peak at 1--2 h and a secondary peak occurring on days 2--3 followed by a return to preinjection levels by day 7.

Adult↗

Effects of manipulating serotonin on the incidence of ovulation in the rat.

Previous studies have shown that while depletion of brain serotonin by the administration of p-chlorophenylalanine (PCPA), an inhibitor of tryptophan hydroxylase, blocks the daily surge of LH in oestrogen-treated ovariectomized rats, restoration of serotonin synthesis by treatment with its immediate precursor, 5-hydroxytryptophan (5-HTP), at a critical time of day, reinstates the surge. The present study indicates that the experimental procedure involving serotonin depletion and its subsequent replenishment may also be used to control the preovulatory LH surge and ovulation in intact cyclic rats provided that (1) the PCPA is administered subcutaneously rather than intraperitoneally nad (2) the 5-HTP is given in conjunction with carbidopa, a peripheral decarboxylase inhibitor: the latter observation providing further evidence for a central role for serotonin in the control of ovulation. These precautions were unnecessary when oestrogen was administered at the same time as the PCPA. It appears that PCPA administered intraperitoneally results in a suppression of the preovulatory rise in oestrogen secretion (and may have additional deleterious effects at the level of the ovaries) and that 5-HTP, in the absence of supplementary oestrogen, may block ovulation by peripheral action after conversion to serotonin. This study indicates the need for caution when using pharmacological 'cocktails' to investigate neuroendocrine events underlying ovulation when the experiments are carried out in the presence of the ovaries.

5-Hydroxytryptophan↗

The environment of cytochrome P-450 in testicular microsomes.

The effects of trypsin, phospholipase A, and chymotrypsin on NADPH-cytochrome c reductase and cytochrome P-450 of microsomes from cryptorchid mouse testes and liver were compared. Trypsin released both enzymes almost completely from testis microsomes, while it readily released only NADPH-cytochrome c reductase from liver microsomes. Chymotrypsin alone, even under conditions where 30-40% of the microsomal protein was hydrolyzed, had little effect on localization or activity of either enzyme in either tissue. Phospholipase A destroyed cytochrome P-450 in testicular microsomes but had little effect on this enzyme in hepatic microsomes or on NADPH-cytochrome c reductase in either preparation. When, however, the microsomes were incubated with chymotrypsin in the presence of a detergent, the effects were similar to those of trypsin alone; testicular cytochrome P-450 was destroyed, while hepatic cytochrome P-450 was only slightly solubilized, and NADPH-cytochrome c reductase from both types of microsomes was both solubilized and activated. From these results we conclude that arginyl and/or lysyl bonds may play a significant role in the junction between the hydrophobic region of the membrane and the anchor region of the reductase molecule and that cytochrome P-450 of testicular microsomes is more superficially located in the lipid bilayer than is hepatic microsomal cytochrome P-450.

Animals↗

Clinical significance of plasma drug and prolactin levels during acute chlorpromazine treatment: a replication study.

Nineteen patients with acute psychoses, the majority schizophrenics, were studied in the course of chlorpromazine (CPZ) treatment. Plasma levels of the drug, plasma prolactin (PRL), extrapyramidal side-effects (EPS) and changes in mental state were monitored weekly, as in our earlier study. The results confirm some of our previous findings: (a) plasma CPZ levels vary widely among patients and correlate poorly with daily doses of CPZ; (b) increased plasma PRL is associated with higher plasma CPZ levels and is more common among the patients who develop EPS; and (c) none of these three variables differ between groups of patients with good and poor treatment outcome. However we did not confirm our previous finding of a significant association between EPS and higher plasma CPZ, nor did we find that the ratio of CPZ-sulphoxide to CPZ differed between the improved patients and the rest.

Adult↗

Effect of temperature on diauxic growth with glucose and organic acids in Pseudomonas fluorescens.

Growth of Pseudomonas fluorescens in batch culture with glucose and organic acids resulted in typical diauxic responses at 30 degrees C but no detectable diauxic lag at 5 degrees C. At 30 degrees C, organic acids were preferentially utilized during the first growth phase. Glucose utilization was delayed until onset of the second growth phase. Systems involved in direct uptake and catabolism of glucose responded in a manner compatible with repression by malate and/or its metabolites and induction by glucose and/or its metabolites. The oxidative non-phosphorylated pathway, through gluconate and 2-ketogluconate (2-KG) as intermediates, was not induced during either growth phase. At 5 degrees C, growth with glucose and organic acids was biphasic but without diauxic lag. Organic acids were preferentially utilized during the first growth phase. Although carbon from glucose was not fully catabolized until onset of the second growth phase, glucose was oxidized to and accumulated extracellularly as gluconate and 2-KG during the first growth phase. No significant repression of glucose-catabolizing enzymes was observed during growth with organic acids in the presence of glucose. However, uptake activities for gluconate and 2-KG did not increase significantly until onset of the second growth phase. Thus, at low temperatures, psychotrophic P. fluorescens oxidized glucose to extracellular 2-KG, while growing on preferred carbon sources. The 2-KG was then catabolized after depletion of the organic acid.

Carboxylic Acids↗