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Biomedical subjects

P Collins

Publications and source records attributed to P Collins.

At least 307 records · Page 17Linked to original sources
PubMed1987

Antisecretory activity of misoprostol, its racemates, stereoisomers and metabolites in isolated parietal cells.

Inhibition of histamine-stimulated acid secretion by misoprostol was compared to its racemates, stereoisomers and metabolites in isolated canine parietal cell preparations. The concentration of misoprostol required to inhibit 50% of maximal histamine-stimulated acid secretion (IC50) was 3.8 +/- 0.3 nM. One racemate of misoprostol was at least 1000 times more potent than the other. Of the four misoprostol stereoisomers, the 11R, 16S isomer exhibited the most potent activity against histamine with an IC50 value of 1.4 +/- 0.1 nM. The acid metabolite of misoprostol was equally potent as misoprostol. In contrast to the acid metabolite, the beta-oxidation metabolites of misoprostol lacked significant activity at 1 microM. The results indicate that: 1) the acid metabolite of misoprostol may play a significant role in the antisecretory activity of misoprostol, and 2) the high degree of stereo-specificity associated with the antisecretory effects indicates that the activity of misoprostol may be receptor mediated.

Alprostadil↗
PubMed1987

The perchlorate discharge test for examining thyroid function in rats.

A perchlorate discharge test was developed for rats to detect changes in the thyroidal iodide accumulation and organification mechanisms. Rats were pretreated with compounds that alter thyroid function by different mechanisms: SK&F 93479 (an H2-antagonist that enhances pituitary thyroid stimulating hormone drive by increasing thyroid hormone clearance) and propylthiouracil (an inhibitor of iodide organification). Six hours following administration of 125I, either potassium perchlorate (10 mg/kg x 2.5 min) or saline was given i.p. Perchlorate significantly reduced the thyroid: blood 125I ratio in propylthiouracil-treated rats but had no effect in those pretreated with SK&F 93479, indicating an iodide organification block in the former. At the same time thyroidal radioiodide accumulation in SK&F 93479-treated rats (no perchlorate) was enhanced, whereas that in propylthiouracil-treated animals (no perchlorate) was depressed.

Animals↗
PubMed1987

Studies on the effect of chronic L-triiodothyronine (T3) treatment on brain Na+,K+-ATPase activity in the mature rat.

Mature rats were dosed with T3 by different routes and dose-levels at either 0.1 mg/kg for 14 days s.c. (Group A), 1 mg/kg for 3 alternative days i.p. (Group B), 5 mg/kg for 14 days p.o. (Group C), or with propylthiouracil (PTU 50 mg/day for 14 days p.o.-Group D). Measurement of cerebellar and striatal NA+,K+-ATPase activities showed that whereas Groups A, B and D were unaffected when compared with controls, there were 35-70% increases respectively in the activities of both molecular forms of the enzyme, alpha(+), high ouabain affinity, and alpha, low ouabain affinity, in Group C rat brains at the highest dose of T3 tested. Kidney Na+,K+-ATPase activity was also elevated (67% increase) in this group of animals showing significant changes in renal medullary tissue only. Acute elevation of brain dopamine levels by administration of an MAOI plus L-DOPA (50 mg/kg, 60 min) significantly elevated (20% increase) the activities of both molecular forms of Na+,K+-ATPase in corpus striatum. Treatment with L-tryptophan (50 mg/kg, 60 min) failed to produce any changes in the striatal activities. The possible relationship of increases in enzyme activities with T3 and increased brain monoamine function is discussed. Both plasma free T4(FT4) and total T4(TT4) were markedly depressed in all T3-treated rats. Although hypothalamic thyrotropin releasing hormone (TRH) concentrations were unaltered by any of the T3 treatments, pituitary thyroid stimulating hormone (TSH) concentrations were greatly diminished and it is thought that this may reflect a direct effect of T3 on TSH synthesis.

Animals↗
PubMed1987

High concentrations of neuropeptide Y in pituitary portal blood of rats.

Pituitary portal blood was collected from urethane-anesthetized rats and examined for the presence of neuropeptide Y (NPY) using high-performance liquid chromatography and radioimmunoassay. Other rats were perfused with fixative, and coronal sections through the hypothalamus and median eminence were processed for immunohistochemical localization of NPY. Combined high-performance liquid chromatography and radioimmunoassay analysis of pituitary portal plasma and systemic plasma revealed a single peak of NPY immunoreactivity which corresponded in retention time to synthetic porcine NPY. Increasing amounts of portal or systemic plasma produced displacement curves which were parallel to the NPY standard curve. The concentration of NPY immunoreactivity in portal plasma (52.0 +/- 4.0 ng/ml, mean +/- SEM) was three times greater (p less than 0.005) than in systemic plasma (16 +/- 4.5 ng/ml). NPY-labeled fibers were observed in the external zone of the median eminence in the vicinity of hypothalamo-hypophyseal portal vessels. The observation of significantly higher concentrations of NPY immunoreactivity in the portal plasma supports the hypothesis that NPY may be released from the hypothalamus to affect pituitary function.

Animals↗
PubMed1987

Plasma catecholamines and lipoproteins in chronic psychological stress.

Changes in plasma catecholamines, lipoproteins and dietary intake were examined in 13 medical students during a 3-month period prior to their examinations, and in 12 controls. In the medical students mean +/- s.e.(mean) plasma cholesterol increased over the study period (3.98 +/- 0.16 v. 4.26 +/- 0.16 mmol/l, P less than 0.05) and this was reflected by a rise in low-density lipoprotein cholesterol (2.53 +/- 0.15 v. 2.71 +/- 0.17 mmol/l, P less than 0.05). Both supine adrenaline (0.45 +/- 0.05 v. 0.70 +/- 0.07 nmol/l, P less than 0.01) and noradrenaline (2.74 +/- 0.18 v. 3.40 +/- 0.31 nmol/l, P less than 0.05) increased over this period. Apart from a decline in the modest alcohol consumption (9.1 +/- 3.45 v. 2.6 +/- 1.4 g/day, P less than 0.02) there was no change in dietary intake in the medical students. There were no significant changes in plasma catecholamines, lipoproteins or dietary intake in control subjects over the study period. Changes in catecholamines and lipoproteins occurring in association with chronic psychological stress may contribute to the increased coronary heart disease mortality associated with Type A behaviour and stressful life events.

Adult↗
PubMed1986

Sensitivity monitoring of herpes simplex virus isolates from patients receiving acyclovir.

A simple plaque-reduction assay was used to determine the acyclovir sensitivity of herpes simplex virus isolates taken from patients enrolled int he acyclovir clinical trial programme. The resultant data revealed no reduction in acyclovir sensitivity in virus from those patients, with a normal immune status, receiving topical, oral or intravenous acyclovir for the treatment of acute disease episodes. In the treatment or prophylaxis of chronic herpes infections in immunocompromised patients reductions in sensitivity were observed but these were infrequent. Sensitive virus was later recovered from a small number of patients who had yielded resistant virus when they were followed through to the next recurrence.

Acyclovir↗
PubMed1986

Antiviral activity of the polybasic anion, suramin and acyclovir in Hepadna virus infection.

Acyclovir and suramin were examined for their efficacy alone and in combination against duck hepatitis B virus (DHBV) in persistently infected Pekin ducks. In ducks the peak plasma concentration of acyclovir was reached thirty minutes after oral administration. Oral acyclovir and suramin administered intravenously suppressed the replication and production of infectious virions as measured by marked reduction of DNA polymerase activity during treatment. However, rebound of enzyme activity was observed soon after cessation of drug therapy. In contrast, sustained reduction of polymerase activity was attained by combined therapy of acyclovir followed by suramin, demonstrating a significant enhancement of anti-DHBV activity which requires confirmation in a larger experimental study. This report establishes that the duck model is ideal for screening antiviral compounds in treatment of infection with Hepadna viruses.

Acyclovir↗
PubMed1986

Antianginal and haemodynamic effects of alpha 1-adrenoceptor blockade.

We studied the effects of alpha 1-adrenoceptor blockade with indoramin on exercise tolerance in 15 patients with chronic stable angina using a double-blind crossover protocol. Thirteen patients had been receiving beta-adrenoceptor blocking drugs and nitrates. The therapy of these patients was continued unchanged throughout the study. Indoramin, in a dose of 25 mg three times daily, prolonged exercise duration by 17% (p less than 0.01) and increased oxygen consumption during exercise by 21% (p less than 0.01), while the maximal double product was unchanged. This increase in exercise capacity was associated with significant attenuation in ST segment depression during exercise. To investigate the mechanism of this antianginal effect, we studied the effects of indoramin (0.2 mg/kg i.v.) on coronary and systemic haemodynamics in a further 11 male patients with chronic stable angina who were receiving beta-adrenoceptor blocking drugs. Measurements were obtained during sinus rhythm and during atrial pacing from 100 beats/min, incremented by 20 beats/min at intervals of 3 min until the onset of angina. Indoramin had no effect on resting heart rate (64 +/- 2 vs. 67 +/- 2 beats/min), but did prolong pacing time to angina (7.4 +/- 0.7 vs. 5.4 +/- 0.5 min; p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1986

Endothelium-derived relaxing factor alters calcium fluxes in rabbit aorta: a cyclic guanosine monophosphate-mediated effect.

1. Measurement of tension and 45Ca influx and efflux were used to study the effects of endothelium-derived relaxing factor (EDRF), sodium nitroprusside and 8-bromo-cyclic guanosine monophosphate (GMP) on contractile responses and calcium movements in aortic ring preparations of the rabbit. 2. EDRF activity, induced by stimulating endothelium-containing rings with acetylcholine, was associated with relaxation of noradrenaline-constricted rings and with a marked reduction of noradrenaline-stimulated increase in calcium influx. Sodium nitroprusside and 8-bromo-cyclic GMP had a similar effect in de-endothelialized preparations. 3. EDRF also inhibited noradrenaline-stimulated calcium efflux. Sodium nitroprusside and 8-bromo-cyclic GMP had a similar effect in de-endothelialized preparations, both in the presence and absence of extracellular calcium. 4. The vascular smooth muscle relaxant effect of EDRF and of nitrovasodilators may be effected by a cyclic GMP-mediated reduction of cytosolic calcium, through both inhibition of calcium influx and reduction of intracellular calcium release.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1985

Comparison of the pathogenicity of Mycobacterium paratuberculosis and Mycobacterium spp isolated from the wood pigeon (Columba palumbus-L).

The pathogenicity of 4 strains of mycobacteria isolated from wood pigeons and 2 strains of Mycobacterium paratuberculosis was compared in calves, mice and chickens. Three of the 4 wood pigeon strains and the 2 M. paratuberculosis strains produced clinical Johne's disease in calves. All 6 strains were pathogenic for mice and the 4 wood pigeon strains were pathogenic for chickens. The strains were not agglutinated by antisera to strains of the M. avium complex and all were mycobactin-dependent. It was concluded that the wood pigeon isolates may constitute a distinct group with the pathogenic capability of M. avium in chickens and M. paratuberculosis in calves.

Animals↗
PubMed1985

Comparison of the in vitro and in vivo antiherpes virus activities of the acyclic nucleosides, acyclovir (Zovirax) and 9-[(2-hydroxy-1-hydroxymethylethoxy)methyl]guanine (BWB759U).

The antiherpes virus activities of acyclovir and its close analogue 3-[(2-hydroxy-1-hydroxymethylethoxy)methyl]guanine (BWB759U) were compared in vitro and in vivo. The activities of both compounds against herpes simplex virus and varicella-zoster virus were similar in the majority of cell lines. However, in mouse-derived and HeLa cells, BSB759U was more effective than acyclovir against herpes simplex virus. Mutants of herpes simplex virus deficient in thymidine kinase and resistant to acyclovir were found to vary in their sensitivity to BWB759U. In two mouse models of herpes simplex virus infection BWB759U was more effective than acyclovir.

Acyclovir↗
PubMed1985

Modifications on the heterocyclic base of acyclovir: syntheses and antiviral properties.

A group of compounds was prepared in which variations of the ring portion of the acyclovir (ACV) structure were made. These modifications included monocyclic (isocytosine, triazole, imidazole), bicyclic (8-azapurine, pyrrolo[2,3-d]pyrimidine, pyrazolo[3,4-d]pyrimidine) and tricyclic (linear benzoguanine) congeners. The derivatives were evaluated against herpes simplex virus type 1 (HSV-1) by the plaque-inhibition and plaque-reduction methods with only the 8-azapurine analogue 28 showing some activity. In a test measuring the ability of these compounds to inhibit the HSV-1 thymidine kinase, 28 and the tricyclic derivative 38 exhibited competition with ACV for binding to the enzyme. The inability of the group to exert significant antiherpetic action is attributed to their lack of phosphorylation to the requisite triphosphate stage.

Acyclovir↗
PubMed1985

Psychological, nutritional and physical status of olympic road cyclists.

Six members of the Irish Olympic Road Cycling Squad underwent a comprehensive medical, nutritional, psychological and biochemical assessment in January 1983. They were given specific medical and dietary recommendations and were reassessed in January 1984 after a period spanning the competitive racing season. The cyclists' diets at both sessions were comparable and generally conformed with recommended daily intakes. Supplementary ingestion was unnecessary to attain recommended daily intakes of vitamins. Serum levels of HDL-cholesterol increased and triglyceride decreased during the period of the study. The squad had characteristics indicating traits of self-sufficiency, toughness and practical mindedness. At the second assessment there was evidence of heightened ambition and competitiveness and an improvement in mood states with reduced ratings for confusion and tension.

Adult↗
PubMed1985

Improvement in angina pectoris with alpha adrenoceptor blockade.

The effects of indoramin, a selective alpha 1 adrenoceptor antagonist, on exercise tolerance were studied in 15 patients using a random double blind crossover protocol. All patients had chronic stable angina, for which 13 had been receiving beta adrenoceptor blocking drugs and nitrates, and these were continued unchanged throughout the study. An initial open challenge with indoramin in eight patients with chronic stable angina showed no serious adverse effects. In a dose of 25 mg three times daily indoramin prolonged exercise duration and increased oxygen consumption during exercise, while the maximal double product was unchanged. The increased exercise capacity was associated with a reduction in ST segment depression during exercise. Side effects included failure of ejaculation in one patient and tiredness in five. These results indicate than alpha 1 adrenoceptor blockade may provide useful additional benefit to patients with stable angina pectoris who are already receiving beta blockers and nitrates.

Adrenergic alpha-Antagonists↗