Biomedical subjects

A Manning

Publications and source records attributed to A Manning.

At least 37 records · Page 2Linked to original sources

PubMed1995

SR 33589, a new amiodarone-like antiarrhythmic agent: anti-adrenoceptor activity in anaesthetized and conscious dogs.

We have assessed the ability of amiodarone and the new amiodarone-like antiarrhythmic agent, SR 33589 (N,N-dibutyl-3-[4-((2-butyl-5-methylsulphonamido)benzofuran-3-yl-c arbonyl) phenoxy]propylamine), to inhibit the effects of adrenoceptor stimulation in anaesthetized and conscious dogs. In anaesthetized, atropinized dogs, adrenoceptor stimulation was achieved (i) by i.v. administration of adrenaline and measurement of increased blood pressure (ii) by i.v. administration of isoprenaline and measurement of increased heart rate and decreased blood pressure. In conscious dogs, adrenoceptor stimulation was achieved by i.v. administration of isoprenaline and measurement of increased heart rate. In anaesthetized, atropinized dogs, both amiodarone and SR 33589 inhibited to similar extents, alpha-adrenoceptor stimulation (as indicated by attenuation of adrenaline-induced increases in blood pressure). The beta 1-adrenoceptor inhibitory activity of SR 33589 (as demonstrated by blockade of isoprenaline-induced increases in heart rate) was significant, but less marked than amiodarone (heart rate elevation reduced by 39%, P < 0.001 with 10 mg/kg SR 33589 and by 52%, P < 0.01 with 10 mg/kg amiodarone). In contrast, its beta 2-adrenoceptor antagonistic activity (as demonstrated by blockade of isoprenaline-induced reduction in blood pressure) was more marked (mean blood pressure decrease reduced by 69%, P < 0.01 with 10 mg/kg SR 33589 and by 31%, P < 0.05 with 10 mg/kg amiodarone). In conscious dogs, both SR 33589 and amiodarone (12.5, 25 and 50 mg/kg p.o.) inhibited isoprenaline-induced increases in heart rate by approximately the same amount for varying durations depending on the dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1995

SR 33589, a new amiodarone-like antiarrhythmic agent: electrophysiological effects in anesthetized dogs.

We compared the electrophysiological effects of a new amiodarone-like agent, SR 33589, with those of amiodarone. Mongrel dogs were anesthetized with chloralose, and electrodes were implanted in right atrium and ventricle for electrical stimulation and regional ECG measurement. Sinus cycle length (CL), AH interval, Wenckebach CL (WCL), atrial, atrioventricular node, and ventricular effective refractory periods (AERP, AVNERP, VERP), and parameters calculated from surface ECG were measured. SR 33589 was administered intravenously (i.v.) at 1, 2.5, or 5 mg/kg followed 60 min later by a second similar dose. The same protocol was followed with amiodarone 5 mg/kg, which reduced heart rate (HR) by 19% (p < 0.05), increased WCL by 31% (p < 0.01), AH interval by 14% (p < 0.05) and AERP, AVNERP, and VERP by 13% (p < 0.05), 19% (p < 0.05), and 11% (p < 0.01) respectively. No effect was observed on HV or PQ intervals. A second administration of 5 mg/kg changed these indexes further. SR 33589 (2.5 mg/kg) reduced HR by 21% (p < 0.001), increased WCL by 44% (p < 0.001), AH interval by 24% (p < 0.01), and AERP, AVNERP, and VERP by 17% (p < 0.001), 63% (p < 0.01), and 15% (p < 0.01) respectively, with an 18% increase in PQ interval (p < 0.05) but no significant effect on HV interval. Higher doses (5 mg/kg) and/or administration of a second dose both resulted in greater changes. Both amiodarone and SR 33589 prolonged VERP more at longer CL than at shorter CL, but the degree of reduction at shorter CL was less with SR 33589 than with amiodarone. Results suggest that acute administration of SR 33589 results in electrophysiological actions similar to those produced by amiodarone.

Amiodarone↗

PubMed1995

Effects of a new amiodarone-like agent, SR 33589, in comparison to amiodarone, D,L-sotalol, and lignocaine, on ischemia-induced ventricular arrhythmias in anesthetized pigs.

We compared the ability of a new amiodarone-like agent, SR 33589, with that of amiodarone, D,L-sotalol, and lignocaine to reduce the incidence of ventricular fibrillation (VF) and associated arrhythmias caused by acute coronary artery occlusion in anesthetized pigs. Ischemia was induced by occlusion of the left coronary descending artery (LAD) for 30 min. Premature ventricular complexes (PVCs), ventricular tachycardia (VT), and ventricular fibrillation (VF) were recorded during coronary occlusion. SR 33589 (1.25, 2.50, and 5 mg/kg intravenously, i.v.) markedly reduced the occurrence of ventricular arrhythmias during ischemia. The incidence of VF was reduced from 90% in the control group to 30% (p < 0.05) with 1.25 mg/kg, to 10% (p < 0.001) with 2.50 mg/kg, and to 20% (p < 0.01) with 5 mg/kg. In addition, SR 33589, especially at the two higher doses, caused a sustained reduction in both the incidence of VT and the number of PVCs per minute. In comparison, amiodarone 10 and 20 mg/kg i.v. reduced the incidence of VF (40 and 50%, respectively), but these reductions never reached a level of statistical significance. The incidence of VT and the number of PVCs per minute were also decreased significantly by amiodarone. D,L-sotalol 3 mg/kg i.v. exerted significant anti-arrhythmic activity; the incidence of VF was reduced 20% (p < 0.01), and both the incidence of VT and number of PVC per minute were also reduced. In contrast, lignocaine given as a 2-mg/kg bolus followed by an infusion at 70 micrograms/kg/min had no antiarrhythmic or antifibrillatory activity in this preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiodarone↗

PubMed1995

Regional differences in constitutive and induced ICAM-1 expression in vivo.

The aim of the present study was to characterize and compare the expression of intercellular adhesion molecule 1 (ICAM-1) on unstimulated and endotoxin-challenged endothelial cells in different tissues of the rat. ICAM-1 expression was measured using 125I-labeled anti-rat ICAM-1 monoclonal antibody (MAb) and an isotype-matched control MAb labeled with 131I (to correct for nonspecific accumulation of the binding MAb). Under baseline conditions, ICAM-1 MAb binding was observed in all organs. The binding of 125I-ICAM-1 MAb varied widely among organs, with the largest accumulation (per g tissue) in the lung, followed by heart (1/30th of lung activity), splanchnic organs (1/50th of lung activity), thymus (1/100th of lung activity), testes (1/300th of lung activity), and skeletal muscle (1/800th of lung activity). Endotoxin induced an increase in ICAM-1 MAb binding in all organs except the spleen. Endotoxin-induced upregulation of ICAM-1 was greatest in heart and skeletal muscle (5- to 10-fold), whereas the remaining organs exhibited a two- to fourfold increase in ICAM-1 expression. Maximal upregulation of ICAM-1 occurred at 9-12 h after endotoxin administration. A dose-dependent increase in ICAM-1 expression was elicited by 0.1-10 microgram/kg, with higher doses (up to 5 mg/kg) producing no further increment. Induction of ICAM-1 mRNA after endotoxin was observed in all tissues examined (lung, heart, intestine), peaked at 3 h, and then rapidly returned to control levels. These findings indicate that ICAM-1 is constitutively expressed on vascular endothelium in all organs of the rat and that there are significant regional differences in the magnitude and time course of endotoxin-induced ICAM-1 expression.

Animals↗

PubMed1994

A mouse model of early social interactions after prenatal drug exposure: a genetic investigation.

The aim of the present study was to (i) characterise the mouse behavioural profile (particularly social interactions) during the preweaning period, (ii) assess the effects of prenatal exposure to an anticonvulsant drug widely used in clinical practice, (iii) examine possible genetic differences both in baseline behavioural profiles and in sensitivity to drug-induced effects. Following a balanced intra-strain fostering procedure, the offspring of C57BL/6J and CBA inbred mouse strains from mothers exposed during pregnancy to either phenobarbitone (PHB, 60 mg/kg) or vehicle (VEH) given intraperitoneally (IP) during days 10-16 of gestation, were observed for early social interactions in the home cage during the last part of the preweaning period (days 20 and 21). The behavioural repertoires of the two strains differed markedly, in that C57 pups were more involved in Play soliciting, Locomotor-rotational play, and in Maintenance activities, while CBA mice spent much more time being inactive or exploring the environment. C57 and CBA mice also differed in the sensitivity to PHB exposure. On the whole, time spent in Investigative/Affiliative behaviours was increased, while the frequency of Play soliciting patterns was reduced in PHB-treated mice. The treatment of the fostering mother had only negligible effects, suggesting that PHB-induced changes in behaviour were largely due to direct effects of the substance on the foetus. These results indicate that specific items of the preweaning behavioural profile, and particularly social interactions, are influenced by early PHB exposure, and that the responses are heavily affected by the genotype.

Animals↗

PubMed1994

Fantofarone (SR33557): effects on myocardial oxygen consumption and coronary blood flow.

We have investigated the effects of a novel calcium antagonist, fantofarone (SR 33557) on myocardial oxygen consumption (MO2C) and coronary blood flow in anaesthetized dogs during periods of normal and elevated heart rate. 25 micrograms/kg i.v. fantofarone induced a transient increase in coronary blood flow (+25% after 2 min; p < 0.05) and a more sustained decrease in MO2C (-50% after 5 min; p < 0.05). During the periods of pacing, these alterations on cardiac function were not evident. Administration of 50 micrograms/kg i.v. resulted in similar modifications of cardiac function; however, these changes were apparent for a longer duration. Coronary blood flow was still significantly elevated by 29% 2 min after drug administration (p < 0.01) and MO2C was reduced by 67% after 5 min (p < 0.01) and by 56% after 30 min (p < 0.05). Most importantly, a significant decrease in MO2C was observed during the pacing periods (32% after 10 min; p < 0.01). Thus fantofarone can significantly modify cardiac function and in particular, decrease MO2C consumption during periods of elevated heart rate.

Animals↗

PubMed1993

Alterations to the pattern of ultrasonic calling after prenatal exposure to aluminium sulfate.

Pregnant CBA mice were exposed to aluminium sulfate at a dose of 200 mg/kg body wt injected intraperitoneally during Days 10 to 13 of gestation. We used a variety of ethological measures, which have been shown to be sensitive indicators of toxicants, to assess effects on the mother and the behavioral development of pups. Prenatal aluminium resulted in a reduction in the rate of ultrasonic calling by pups accompanied by a shift in the timing of peak calling; treated pups exhibited decreased growth and delays in neurobehavioral development. The treatment received by a pup's foster mother was also found to influence development. We recommend ultrasonic calling as a sensitive measure in studies of behavioral teratogenicity.

Abnormalities, Drug-Induced↗

PubMed1993

Behavioural effects of gestational exposure to aluminium.

The involvement of aluminium in the aetiology of a number of human pathological diseases has altered its status from being a nontoxic, nonabsorbable, harmless element. This maybe of particular concern to the developing foetus which is more susceptible to agents and at lower levels than the adult. Little attention has been given to aluminium's potential reproductive toxicity until recently and further research is required for a full evaluation of its toxicity. Our preliminary results demonstrate behavioural and neurochemical alterations in the offspring of mice exposed to aluminium during gestation. Further, the effects of such exposure are also present in the adult animal suggesting persistent changes in behaviour following prenatal exposure.

Abnormalities, Drug-Induced↗

PubMed1992

Fantofarone (SR 33557): effect on post-ischaemic functional recovery in perfused rat hearts.

Fantofarone (SR 33557) is a novel, highly potent calcium channel antagonist representative of a new class of slow channel blockers. In this study, we have assessed its ability to influence cardiac function in two, isolated, perfused heart models and then assessed its ability to modify post-ischaemic functional recovery. In isolated, rat hearts perfused in the Langendorff mode, fantofarone increased coronary flow by 25% at 100 and 1000 nM with no effect on left ventricular pressure or heart rate below 100 nM. In working hearts, fantofarone again increased coronary flow within a similar concentration range. A significant reduction (approximately 40%) was observed in peak systolic pressure and dP/dtmax when hearts were perfused with 1000 nM fantofarone. Working rat hearts were also subjected to a 30 min period of global, low-flow (0.1 ml/min) ischaemia, followed by a 30 min period of reperfusion. Perfusion with 1 or 10 nM fantofarone, began 20 min prior to the onset of ischaemia and continued throughout the ischaemic and reperfusion periods. The addition of 1 nM fantofarone did not cause a significant increase in the recovery of cardiac function during the reperfusion phase. In contrast, perfusion with 10 nM fantofarone resulted in a substantial increase in the recovery of several indices of cardiac function such as aortic output, dP/dtmax and peak systolic pressure. Thus, in the working rat heart, at concentrations which cause minimal alterations to normal cardiac function, fantofarone can improve significantly functional recovery following an ischaemic insult.

Animals↗

PubMed1992

Long-term effects of aluminium on the fetal mouse brain.

Potentially noxious substances may act as fetal teratogens at levels far lower than those required to produce detectable effects in adults, and behavioural teratogenicity may occur at levels lower than those which produce morphological teratogenesis. Aluminium (Al) is a potential neurotoxin in adults. Since pregnant women may be exposed to untoward levels of Al compounds under certain conditions, we have examined the long-term effects of treating the pregnant mouse with intraperitoneal or oral aluminium sulphate on brain biochemistry and behaviour of the offspring. The cholinergic system, as evaluated by the activity of choline acetyltransferase (ChAT), was affected differentially in different regions of the brain, and still showed significant effects in the adult. Differences between the intraperitoneal and oral series in the magnitude of effect seen in the regions of the brain probably reflect differences in the effective level of exposure. Growth rate and psychomotor maturation in the pre-weaning mouse were affected in the intraperitoneal series only, showing a marked post-natal maternal effect.

Administration, Oral↗

PubMed1991

Fine needle cytodiagnosis of renal tuberculosis.

A total of 8 patients in whom renal tuberculosis was suspected on clinical or radiological grounds but in whom confirmation could not be achieved by urine culture underwent renal fine needle aspiration. Immediate cytodiagnosis was accomplished in 7 of 8 patients by the finding of Langhans' giant histiocytes, epithelioid histiocytes and necrotic debris. Later confirmation was obtained in all 8 cases by radiometric culture of aspiration material or saline rinses of the fine needles. This experience introduces fine needle aspiration cytology as a diagnostic modality in renal tuberculosis.

Adult↗

PubMed1990

Genetic differences in maternal behaviour patterns in mice administered phenobarbital during pregnancy.

In a study designed to examine the role of the genotype on sensitivity to drug-induced behavioural changes, pregnant C57BL/6J and CBA mice were administered 60 mg/kg phenobarbital (PHB) intraperitoneally during days 10-16 of gestation. Following a balanced intrastrain fostering procedure, the behaviour of lactating dams was observed in their home cage at 2, 3, 5, 7 and 14 days postpartum. As the pups became older, maternal behaviour declined in control groups, whereas PHB dams of the CBA strain persisted in nursing their pups. C57 dams were generally affected in an opposite way by PHB exposure. For example, treated dams spent significantly less time in licking behaviour. Nest quality score was especially elevated in PHB dams of the CBA strain, while in C57 dams, nest-building was inhibited and nest quality unaffected by the previous PHB exposure. These results indicate that specific items of maternal behaviour can be differently affected by PHB exposure, and that the responses are affected by the genotype. To summarise, pups raised by treated dams may receive either exaggerated or insufficient maternal attention, as a result of changes in neurotransmitter systems and behavioural regulation following phenobarbital exposure. These results point to the need for a better understanding of mother/pup interactions in studies aimed at characterizing drug and toxicant effects on postnatal development.

Animals↗

PubMed1990

Sex, drugs, and HIV infection in a New York City hospital outpatient population.

Persons attending outpatient clinics at Bellevue Hospital Center in Manhattan, New York City were invited to be tested for antibodies to human immunodeficiency virus (HIV). In pretest counseling, males were asked if they had injected nonprescription drugs or engaged in sex with other men since January 1, 1977; if so, they were asked not to participate and were referred elsewhere for testing. Face-to-face interviews and HIV testing were completed for 1,119 subjects with no prior indication of HIV seropositivity. Willingness to participate in the study was significantly greater among women than men and among younger than older persons. After exclusion of two subjects with indeterminate HIV serology, seroprevalence was 6.3% (70/1,117) overall, 7.1% (26/368) among men, and 5.9% (44/749) among women. HIV seropositivity among female i.v. drug users was 37% (27/74). Among heterosexuals without other HIV risk factors, estimated seroprevalences were 2.7% (25/924) overall, 3.3% (10/305) among males, and 2.4% (15/619) among females. Among heterosexual men, the data suggested associations of HIV seropositivity with sex with prostitutes and sex with numerous partners. Multiple logistic regression analysis indicated that significant predictors of HIV infection among women were a history of sexual contact with a male intravenous drug user, recent last use of intravenous drugs, and long duration of residence in New York City. Sexual intercourse with persons from AIDS risk groups was reported by 11% of men and 18% of women. The modal method of birth control reported by both men and women was "no method".

Adult↗

PubMed1990

Looping of chick embryo hearts in vitro.

Heart rudiments were removed from chick embryos at times earlier than any previously reported, and cultured in vitro, in order to test the widely reported view that looping is an intrinsic process. This view is based on experiments that are inadequately reported in certain key details. An organ culture technique was employed which combined ease of observation with good nutrient and mechanical support for the explants. A total of 23 hearts from stages before the onset of looping were examined. Hearts from as early as the six-somite stage looped normally in these experimental conditions. The view that heart looping is an intrinsic phenomenon is therefore confirmed.

Animals↗

PubMed1989

Differential effects of prenatal exposure to phenobarbital on the behaviour and neurochemistry of CBA and C57BL/6J mice.

Pregnant C57BL/6J and CBA mice were administered 60 mg/kg phenobarbital intraperitoneally from days 10 to 16 of gestation. On day 18 of pregnancy half of the control and drug-treated mice were killed and the embryonic brains removed for cell cultures. The remaining mice were allowed to have their litter. After cross-fostering the mice were used for behavioural studies. Pups born to drug-treated CBA mice had birth-weights similar to controls, but their weights had fallen behind controls by day 18 after birth. They were slower at attaining mature responses in tests for sensory motor development and became progressively more hyperactive (three times more active at day 18) compared to controls. Drug-exposed C57 pups also had birth weights similar to controls. After cross-fostering, 19% of control and 31% of drug-exposed pups died, but the remaining drug-exposed pups showed no deficits in weight gain. In contrast to drug-treated CBA pups, drug-exposed C57 pups were slightly quicker in attaining mature responses in some tests. There was no difference in activity between them and their controls. In neurochemical analyses, uptake of neurotransmitters by cerebral cultures from CBA showed that uptake of GABA was increased by 5%, choline by 95%, dopamine 120%, serotonin 165% and noradrenaline by 160% in cultures from drug exposed embryos compared to controls. In cerebral cultures from C57, GABA uptake was reduced by 18%, choline 33%, dopamine 35% and noradrenaline by 25%. Only serotonin uptake was increased by 182% compared to controls. Differences between C57 and CBA were also apparent in the uptake of neurotransmitters by neuronal cultures from the mesencephalon.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1988

Reperfusion-induced arrhythmias: a study of the role of xanthine oxidase-derived free radicals in the rat heart.

We have assessed whether oxygen-derived free radicals produced by xanthine oxidase may be an important trigger mechanism in the genesis of reperfusion-induced arrhythmias. We have examined (i) the effects of inhibition of xanthine oxidase by both folic acid solution and amflutizole; (ii) the effects of the inhibitor of xanthine dehydrogenase to xanthine oxidase conversion, soybean trypsin inhibitor; (iii) the effects of administration of superoxide dismutase and catalase, both singly and in combination and (iv) in an isolated rat heart preparation we have investigated the ability of free radical scavengers to reduce reperfusion arrhythmias caused by the infusion of xanthine oxidase and hypoxanthine. The prior administration of folic acid solution, amflutizole, superoxide dismutase, catalase, and superoxide dismutase plus catalase all reduced the incidence of reperfusion-induced arrhythmias and resultant mortality, caused by reperfusion after a transient period of coronary artery occlusion in the anaesthetised rat. Prior administration of soybean trypsin inhibitor significantly reduced mortality. In an isolated, perfused rat heart preparation with temporary coronary artery occlusion, addition of xanthine oxidase-hypoxanthine to the perfusion medium increased the incidence of reperfusion arrhythmias and decreased the total duration of sinus rhythm during reperfusion. Further addition of superoxide dismutase or L-methionine increased significantly the total duration of sinus rhythm. These results suggest that in the rat heart xanthine oxidase may be involved in the genesis of reperfusion-induced arrhythmias.

Allopurinol↗

PubMed1988

Measurement of the transfer of the nitrogen moiety of intestinal lumen glutamic acid in man after oral ingestion of l-[15N]glutamic acid.

1. The measurement of the intestinal metabolism of the nitrogen moiety of glutamic acid has been investigated by oral ingestion of l-[15N]glutamic acid and sampling of arterialized blood. 2. Measurements have been made in six normal adults weighing an average of 72.8 kg ingesting 100 mg of l-[15N]glutamic acid after an overnight fast. 3. Measurement of the enrichment of arterial glutamic acid, glutamine and alanine was by gas chromatography-mass spectrometry. Isotopic enrichment of the amino acids was followed for 150 min after the ingestion of the amino acid. 4. Arterialized venous blood amino acid concentrations, measured by h.p.l.c., demonstrated no significant changes during the course of the experiment. 5. From the observed appearance of label in arterialized glutamic acid, alanine and glutamine, little luminal glutamic acid reaches the extracellular pool. The majority of the administered nitrogen label appears in the arterial alanine and glutamine components.

Administration, Oral↗

PubMed1988

The immunological relationship between canine herpesvirus and four other herpesviruses.

Canine herpesvirus (CHV) was compared with four other herpesviruses by several serological techniques. Cross-neutralization was demonstrated between CHV and herpes simplex virus types 1 and 2 and pseudorabies virus. Non-neutralizing cross-reactions were found with these viruses and also with equine abortion virus and bovine mammillitis virus. The data suggest that CHV is immunologically more closely related to herpes simplex virus than to the other viruses used in this study.

Antibodies, Viral↗