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Biomedical subjects

V Paul

Publications and source records attributed to V Paul.

At least 73 records · Page 4Linked to original sources

Behavioural and biochemical changes produced by repeated oral administration of the insecticide endosulfan in immature rats.

In order to study the response of rats to repeated administration of the insecticide, endosulfan during the period of growth to maturity, food intake, body weight gain, Spontaneous Motor Activity (SMA) and Muscle Coordination (MC) were determined at regular intervals in male immature Wistar rats treated with a tolerated dose of (2 mg/kg/day) orally for 90 days. Twenty-four h after the termination of the treatment, organ weight and protein concentrations were determined. The convulsive action of picrotoxin (4 mg/kg, ip) was tested in another endosulfan-treated group. Food consumption and body weight gain decreased parallely. No changes occurred in the body tissues but for liver which was enlarged and its protein, glutamic oxaloacetic transminase and glutamic pyruvic transaminase concentrations increased. The MC was unaffected. A stimulation of SMA occurred several days (75-90) after commencing treatment and these animals responded greatly than control animals to the convulsive action of picrotoxin. These findings indicated that although endosulfan produced anorexia, there were no signs of undernourishment and motor impairment in these animals. Its toxic action were confined chiefly to the liver and central nervous system.

Alanine Transaminase↗

Effect of intravenous adenosine on human atrial and ventricular repolarisation.

OBJECTIVE: The aim was to assess the effects of therapeutic doses of intravenous adenosine on human atrial and ventricular repolarisation. METHODS: The effects of 6 mg and 12 mg bolus doses of adenosine on the atrial and ventricular monophasic action potentials were studied using the contact catheter technique in 19 patients undergoing routine diagnostic electrophysiology studies. The effect on atrial repolarisation was studied before and after beta blockade in a subgroup of patients. RESULTS: The duration of the monophasic action potential to 90% repolarisation (MAPD90) was measured in all cases. After 6 mg of adenosine the atrial MAPD90 shortened from 227(SD 29) ms to 188(25) ms (p < 0.005); after 12 mg it shortened from 221(31) ms to 168(32) ms (p < 0.001). The maximum shortening was unaltered by propranolol 0.15 mg.kg-1. The ventricular MAPD90 showed no significant change after 12 mg, at 240(32) ms v 234(33) ms. CONCLUSIONS: Therapeutic doses of adenosine shorten the atrial but not the ventricular monophasic action potential duration. The effect is dose dependent and not abolished by beta blockade.

Action Potentials↗

Prediction of antiarrhythmic efficacy of class I and III agents in patients with ventricular tachycardia by signal-averaged ECG analysis.

The effects of procainamide and dofetilide (pure Class III antiarrhythmic agent) on the signal-averaged ECG (SAECG) were examined in relation to the results of programmed ventricular stimulation studies in 25 patients with inducible sustained monomorphic ventricular tachycardia. Procainamide prolonged significantly the total QRS and low amplitude signal durations (140 +/- 31 msec vs 166 +/- 48 msec, P < 0.0001; 50 +/- 25 msec vs 65 +/- 38 msec, P < 0.002, respectively) whereas the root mean square voltage of the last 40 msec of the QRS complex was significantly reduced (22 +/- 21 microV vs 13 +/- 12 microV, P < 0.006). Procainamide was effective (prevention of the inducibility of sustained ventricular tachycardia or prolongation of the cycle length of ventricular tachycardia by > 100 msec) in 15 of 27 drug trials. Of the procainamide induced SAECG changes, the fractional prolongation of the total QRS duration was the best parameter that identified effectively treated patients (24% +/- 16% in responders vs 10% +/- 11% in nonresponders, P < 0.014). A fractional prolongation of the total QRS duration by > 15% identified effectively treated patients with a sensitivity of 87%, specificity of 81%, and an overall predictive accuracy of 84%. Dofetilide did not change the SAECG, and no SAECG parameter predicted the results of programmed ventricular stimulation. The effects of both drugs on the spectral analysis (area ratios) and on the spectral temporal mapping (the values of normality factor) of the SAECG were not consistent. In conclusion, antiarrhythmic efficacy of procainamide can be predicted by the degree of drug induced prolongation of the signal-averaged QRS complex.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Arrhythmia Agents↗

Evidence for a hazardous interaction between ethanol and the insecticide endosulfan in rats.

Protein supplemented diet was protective against the deleterious action of endosulfan on body growth and liver. Hepatomegaly and a reduction of body weight produced concurrently by endosulfan and ethanol were greater in male rats, suggesting that males are more susceptible than female rats to the metabolic stress caused by their interaction. Chronic endosulfan exposure resulted in a prolongation of ethanol sleeping time in female and not in male rats. This finding suggests failure of female rats to metabolize ethanol readily on account of their greater susceptibility than male rats to the hepatotoxic action of endosulfan.

Animals↗

Effects of endosulfan and aldrin on muscle coordination and conditioned avoidance response in rats.

The deteriorative effects after chronic endosulfan exposure on muscle coordination, learning and memory of rats were compared with that produced by aldrin which has been reported to have similar effects in experimental animals. A rota-rod apparatus was used to study the muscle coordination and learning and memory were tested by recording the response to unconditioned and conditioned stimuli using a pole-climbing apparatus. Aldrin but not endosulfan inhibited motor coordination in both sexes. A greater motor deterioration occurred in male group. This finding, together with the previous data which shows inhibition by its metabolite of motor activity, suggests that its metabolic product is responsible for this action. Like aldrin, endosulfan inhibited both learning ability and conditioned avoidance response. A change in the activities of brain monoamines or inhibition of perception and reflexes or both were proposed for these behavioural effects, since the former was reported to be produced by both compounds and the latter was found to occur in aldrin treated rats.

Aldrin↗

Baroreflex sensitivity and electrophysiological correlates in patients after acute myocardial infarction.

BACKGROUND: Several studies have identified transient disturbances of autonomic function during the acute and recovery phases of myocardial infarction, and it has recently been suggested that survivors of acute myocardial infarction with depressed vagal tone may be at increased risk of sudden or arrhythmic death. METHODS AND RESULTS: To investigate this hypothesis, parasympathetic function was assessed by arterial baroreflex sensitivity (BRS) testing (using the phenylephrine method) and by heart rate variability (HRV) analysis from 24-hour Holter recording in 68 patients at day 7-10 after infarction. The relation between autonomic tone and markers of arrhythmic propensity, including programmed ventricular stimulation (PVS) and late potentials in addition to other clinical variables, was examined. BRS for the whole group was 7.0 +/- 4.7 msec/mm Hg and was inversely correlated with age (r = 0.53, p less than 0.001) but not with left ventricular ejection fraction (r = 0.035, p = NS). In those patients in whom sustained monomorphic ventricular tachycardia (SMVT) was induced, BRS was significantly reduced (p = 0.001) as was HRV (p = 0.007) and left ventricular ejection fraction (p = 0.022). The strongest association between any variable (including HRV, BRS, late potentials, left ventricular ejection fraction, exercise testing, Q waves, and infarct site) and the induction of sustained monomorphic ventricular tachycardia was depressed BRS with a relative risk of 36.28 (95% confidence interval, 5-266). CONCLUSIONS: This study confirms that depressed BRS identifies a subgroup at high risk for arrhythmic events after myocardial infarction and that programmed ventricular stimulation may be safely limited to this group without any loss of predictive accuracy.

Arrhythmias, Cardiac↗

Sotalol for paroxysmal supraventricular tachycardias.

Used in adequate dosages, sotalol is efficacious in the conversion of acute supraventricular arrhythmias, an effect that is predictable on the basis of the drug's known electropharmacologic actions. Electrophysiologic studies have shown that both oral and intravenous sotalol are effective in preventing the induction of sustained arrhythmias and that the success of acute suppression is indicative of subsequent clinical control. Interim results of a recent trial of prophylaxis against recurrence of paroxysmal supraventricular tachycardia are reported, demonstrating a high efficacy with an acceptably low profile of adverse effects.

Double-Blind Method↗

A functional interaction between GABA and 5-HT in inhibiting picrotoxin-induced myoclonus in rats.

Pretreatment with 5-hydroxytryptophan (5-HTP), a precursor of 5-HT, antagonised while pretreatment with p-chlorophenylalanine (PCPA), a 5-HT depletor, potentiated the myoclonus induced by picrotoxin, a GABA antagonist. Pretreatment with aminooxyacetic acid (AOAA), a GABA transaminase inhibitor, antagonised picrotoxin-induced myoclonus. The combined effect of the least protective doses of AOAA and 5-HTP was greater than the sum of their individual inhibitory effects on picrotoxin-induced myoclonus. Further, AOAA failed to inhibit picrotoxin-induced myoclonus in PCPA pretreated rats. These findings suggest that the central 5-HT-ergic system exerts a facilitatory influence on the GABA-ergic system and thus it is involved in the antimyoclonic action of GABA.

5-Hydroxytryptophan↗

The synergistic protective effect of propranolol & aminooxyacetic acid against picrotoxin-induced myoclonus in rats.

The effect of propranolol was assessed against myoclonus induced by picrotoxin (a known GABA antagonist) in a dose of 3 mg/kg and allylglycine (the inhibitor of GABA synthesis and release) in a dose of 150 mg/kg. A dose-dependent (0.5-2 mg/kg) protective effect was found against both models. Pretreatment of rats with a GABA-reducing dose (100 mg/kg, nonmyoclonic) of allylglycine produced no change in the effect of propranolol against picrotoxin-induced myoclonus. Propranolol thus inhibited myoclonic responses when both the receptor activity and the functional pool of GABA were impaired, suggesting that it produces as antimyoclonic action without the involvement of GABA. However, the drug seems to show a synergistic action with GABA-ergic agents, as greater protection was observed in rats treated concurrently with propranolol and amino-oxyacetic acid, an inhibitor of GABA degradation.

Acetates↗

Adjuvant xamoterol or metoprolol in patients with malignant ventricular arrhythmia resistant to amiodarone.

In a randomised cross-over study, six patients with recurrent sustained ventricular tachycardia (VT) were treated with 3 regimens--amiodarone, amiodarone plus metoprolol, and amiodarone plus xamoterol. All patients had poor left ventricular function and were resistant to multiple drugs. Xamoterol (a partial beta-agonist) was more effective than metoprolol as adjuvant therapy to amiodarone in the control of recurrent sustained ventricular arrhythmias and was not associated with any clinical deterioration of ventricular function. Xamoterol was also more effective than metoprolol for suppression of VT at programmed stimulation and as effective as metoprolol for suppression of VT on exercise. Exercise tolerance was significantly greater during treatment with xamoterol/amiodarone than during treatment with metoprolol/amiodarone or with amiodarone alone.

Adrenergic beta-Agonists↗

Combination of sensors to provide optimal pacing rate response.

Previously, single-chambered rate-adaptive and dual-chamber pacemakers have been considered as alternative methods of providing rate response. Neither can adapt to changing circumstances and each has its own benefits and limitations. The development of units combining both facilities expands the range of conditions for which atrioventricular sequential pacing is possible and will ensure appropriate and adequate rate response at all times. At present, change in pacing mode is dependent on physician programming, but future generations will have the ability to diagnose the intrinsic rhythm and then prescribe automatically the pacing modality of choice.

Arrhythmias, Cardiac↗

Closed loop control of rate adaptive pacing: clinical assessment of a system analyzing the ventricular depolarization gradient.

Closed loop control of rate adaptive pacing has theoretical advantages over current rate responsive pacemakers. The first available system (which senses the ventricular depolarization gradient) has been evaluated in ten patients. The pacing response to a variety of exercise and nonexercise stimuli was assessed. Response to isotonic exercise was prompt and proportional to the exertion involved while isometric exercise and mental stress produced obvious but more gradual increases in pacing rate. In seven patients, comparison between the intrinsic P wave and pacing rate showed a high correlation during exercise (r = 0.91) and mental activity (r = 0.87). Postural changes induced a paradoxical response. Closed loop rate responsive pacing based upon analysis of the ventricular depolarization gradient produces a fast and appropriate rate response to most physiological stimuli.

Adult↗

Synergistic anticonvulsant action of diazepam & clonazepam with amino-oxyacetic acid against isoniazid-induced convulsions in rats.

The protective effect of two benzodiazepine compounds, diazepam and clonazepam was tested against isoniazid (INH)- induced convulsions in rats pretreated with the gamma-amino-butyric acid (GABA) transaminase inhibitor viz., aminooxyacetic acid (AOAA), and the result was compared with that produced by the two drugs independently. Rats treated 6 h and not 30 min previously with AOAA showed a dose-dependent inhibition of INH-induced convulsions. In these animals both diazepam and clonazepam showed a greater protective effect than that produced by them alone. It is suggested from these findings that, even if their anticonvulsant mechanisms are distinct, with or without the involvement of GABA, AOAA and the benzodiazepine compounds seem to act synergistically against INH-induced convulsions.

Acetates↗

Evidence for synergism between the antimyoclonic actions of 5-hydroxytryptophan and clonazepam in rats.

The protective effect of the precursor of 5-hydroxytryptamine (5-HT), 5-hydroxytryptophan (5-HTP) against myoclonus induced in rats by picrotoxin and allylglycine was demonstrated. The inhibition by 5-HTP of picrotoxin-induced myoclonic movements was found to correlate well with an increased 5-HT release from the cerebral cortex. p-Chlorophenylalanine (PCPA) pretreatment aggravated the actions of both picrotoxin and allylglycine by shortening their myoclonic latencies. These findings suggest that there is an antimyoclonic effect of 5-HT in the brain. The protective effect of clonazepam against these two myoclonic models was found to be potentiated in 5-HTP-pretreated animals. Only a partial inhibition of its protective effect resulted from PCPA pretreatment. These data suggest that a beneficial synergism is likely to occur between 5-HTP and clonazepam for the inhibition of myoclonus and that a 5-HTergic mechanism does not play a significant role in the antimyoclonic action of clonazepam.

5-Hydroxytryptophan↗

Cross-sectional echocardiographic demonstration of biventricular thrombus.

Nine months following extensive myocardial infarction, a 60-year-old man presented with intermittent right heart failure. Cross-sectional echocardiography demonstrated biventricular thrombi, the right ventricular thrombus being very close to the tricuspid valve and possibly interfering with its function. Post-mortem examination confirmed the echocardiographic findings.

Echocardiography↗

Involvement of beta 2-adrenoceptor blockade and 5-hydroxytryptamine mechanism in inhibition of harmaline-induced tremors in rats.

Specific beta 1- and beta 2-adrenoceptor antagonists, acebutolol and butoxamine respectively were used to investigate the involvement of blockade of these receptors in the inhibition of harmaline-induced tremors. Both agents produced an antitremor effect in a dose-dependent manner, with butoxamine showing greater potency than acebutolol. The dose of isoprenaline (0.1 mg/kg) that markedly reduced the effect of butoxamine did not alter the effect of acebutolol, suggesting that antagonism of peripheral beta 1-adrenoceptor was not responsible for the antitremor action of acebutolol and that blockade of peripheral beta 2-receptors is involved to a great extent in the inhibition of tremors by butoxamine. The effect of acebutolol was unaltered in rats pretreated with 5-hydroxytryptophan and p-chlorophenylalanine, which on the other hand produced potentiation and a partial reduction respectively of the action of butoxamine. It appears, therefore, that butoxamine also acts centrally in association with the 5-HT system and that this action is relatively weaker than the peripheral action. The dual action on two sites may account for the potent antitremor action of butoxamine.

5-Hydroxytryptophan↗

The growth and migration of Necator americanus following infection of neonatal hamsters.

Necator americanus was studied in neonatally infected hamsters in order to determine precisely the growth and migration of the parasite in this laboratory host. Most larvae stayed at the skin infection site for at least 48 hours following administration of larvae and the movement to the lungs commenced on day 3. There was no significant growth at the skin site or during the first two days in the lungs. 98% of the larvae were recovered from the lungs by day 6 and showed signs of some growth and development. Moulting larvae were seen in the lungs on days 7 and 8, but intestinal worms, which were first detected on day 7, were all L4 larvae. These worms were significantly longer than the lung stages and henceforth grew rapidly. Over 80% of the worms were recovered from the intestine on day 9, only small numbers of larvae persisting in the lungs until day 12. Moulting worms were observed in the intestine on days 17 to 21, after which growth continued and did not slow until about the fifth week. Small quantities of eggs were occasionally detected as early as day 34 and continuous egg production commenced in the seventh week of infection reaching a peak by about the 10th week.

Animals↗