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Biomedical subjects

P L Sharma

Publications and source records attributed to P L Sharma.

At least 37 records · Page 2Linked to original sources

Effects of post-training administration of (-)-baclofen and chlordiazepoxide on memory retention in ICRC Swiss mice: interactions with GABAA and GABAB receptor antagonists.

The effects of post-training administration of chlordiazepoxide and (-)-baclofen on memory retention was studied in ICRC Swiss mice by measuring the retest stepdown latency 24 hr after foot-shock in a passive avoidance task. Chlordiazepoxide 20 mg/kg impaired memory retention and a similar effect was produced by 10 mg/kg of diazepam. The effect of chlordiazepoxide was antagonised when combined with picrotoxin but not by the addition of a specific GABAB antagonist CGP 35348. The effect of chlordiazepoxide on memory retention seems to be mediated by action at the GABAA-benzodiazepine receptor complex. (-) Baclofen, the active isomer of the GABAB agonist enhanced memory in ICRC mice and this effect was antagonised by CGP 35348 at a dose of 10 mg/kg. The inactive isomer of baclofen, (+)-baclofen did not produce any effect. This indicates that GABAB receptors contribute to the effects of (-)-baclofen on memory.

Animals↗

BRL 38227--a potassium channel opener, antagonizes digoxin-induced convulsions.

Experimental evidence suggests that potassium channel openers play an important role in convulsions. In this study, the anticonvulsant activity of BRL 38227, a new potassium channel opener against digoxin-induced convulsions, is reported. Intraventricular administration of digoxin (7.5 micrograms), included "popcorn-type" convulsions in rats. BRL 38227, injected centrally increased the onset time of convulsions and decreased the mortality rate in a dose-dependent manner. Pretreatment with 4-aminopyridine, a potassium channel blocker antagonized the protective effect of BRL 38227. These findings show the involvement of potassium channels in digoxin-induced convulsions. Further these results indicate that in the future potassium channels might be a target for new anticonvulsant drugs.

4-Aminopyridine↗

Clinical evaluation of the effect of omeprazole, cimetidine, famotidine and ranitidine on histamine induced cutaneous wheal and flare response.

The effect of H2 receptor antagonists on immediate cutaneous response to allergens remain controversial. In the present study, the effect of 7-day administration of omeprazole, cimetidine, famotidine and ranitidine on histamine induced wheal and flare reaction was evaluated. A single blind randomized parallel group study with within patient comparison of responses was planned in non-ulcer dyspepsia patients eligible to receive H2 antagonists or omeprazole. None of the drugs produced any changes in the area of the wheal in comparison to respective baseline values. The area of flare was decreased by all the drugs and the percentage decrease in this parameter caused by omeprazole, cimetidine, famotidine and ranitidine was 2.4, 12.3, 20.2 and 13.2, respectively. Only famotidine caused a significant decrease in flare area (p < 0.05).

Adult↗

Effects of ranitidine alone and in combination with chlorpheniramine on histamine-induced wheal and flare and psychomotor performance.

Some reports suggest that addition of an H2 antagonist increases the efficacy of H1 antagonist but the influence on the side effect profile of antihistamines are largely unknown. The effects of ranitidine, chlorpheniramine, their combination and placebo on histamine induced wheal and flare, psychomotor performance and subjective symptoms were studied in 6 healthy male volunteers in a double blind randomized and cross-over (Latin square) study. Ranitidine significantly reduced the histamine induced wheal at 4 hrs (P < 0.05). Chlorpheniramine and the combination significantly reduced both histamine induced wheal and flare at 2 hrs and at 4 hrs (P < 0.05). Addition of ranitidine reduced the feeling of sleepiness produced by chlorpheniramine, though other subjective symptoms were not affected. None of the treatment schedules produced any consistent change in the psychomotor performance of the volunteers.

Adult↗

A study on withdrawal related haemodynamic response in chronic propranolol treated conscious rats.

Single dose of propranolol hydrochloride (5 mg/kg, i.p.) caused significant fall in heart rate (HR) but not in systolic blood pressure (SBP) in normotensive conscious rats. Multiple doses of propranolol (5 mg/kg, i.p., twice-a-day for 5 wk) caused significant fall in both HR and SBP at 2 wk and 4 wk in normotensive conscious rats. Sudden withdrawal of propranolol at 5 wk caused a significant blood pressure upswing and tachycardia between 12-24 h followed by normalization of both blood pressure and heart rate. The study documents a possible model of rebound hypertension in normotensive conscious rats.

Animals↗

Simian immunodeficiency virus infection via amniotic fluid: a model to study fetal immunopathogenesis and prophylaxis.

The rising prevalence of infection with the human immunodeficiency virus type 1 (HIV-1) in young women will increase the number of infected children worldwide. Because HIV-1 seems to be transmitted mostly intrapartum, fetal infection probably occurs mainly via skin or mucous membrane exposure. A model for this route of fetal infection has been established in primates. After injecting the simian immunodeficiency virus (SIV) into amniotic fluid during late gestation, six of seven rhesus monkeys were born infected. All infected neonates were viable and showed signs of disease, such as low birth weights, lymphadenopathy, and rashes. Cytotoxic T-cell responses to SIV were absent in neonates, but present in mothers. The high fetal infection rate allows studies of lentiviral immunopathogenesis during ontogeny and the development of strategies to prevent maternal HIV-1 transmission.

Amniotic Fluid↗

Prescription drug use in lactating mothers: an experience at a referral hospital and in a community in India.

The aim of the study was to investigate the extent of prescription drugs administered for common disorders during the post partum period. This is a prospective survey of disorders and drug use in 1) immediate postpartum mothers (n = 200) admitted to the maternity wards, 2) in post-natal hospital follow-up clinic (n = 200) and in 3) the rural home based community (n = 100). A pretested questionnaire was filled in by medical officers after interviewing the mothers. The mean age of the mothers was 25 years and a literacy rate of 50% above the 10th grade. Over 80% of the women were multigravida in the entire sample; 45% underwent Caesarean Section in a hospital; 97.6% had a normal delivery in the community. In the hospital settings 4.1% infants had jaundice and 1% had congenital anomalies. In the community setting, diarrhoea and pneumonia was seen in 2.6% of the infants. Apart from the use of nutritional supplements, such as iron, calcium, multivitamins etc., most commonly prescribed drugs were analgesics (in 70% of patients in the hospital settings, 56% of the patients in the postnatal clinic and 37.6% patients in the community), and antibiotics (90% of the patients in the hospital settings, 86% of the patients in the postnatal clinic and 13% of the community based patients). Antihypertensives agents (2.5% of the patients), digoxin (1.5% of the patients), bronchodilators (1% of the patients) and sedatives (3.5% of the patients) were prescribed to admitted patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Comparative bioavailability of two enteric-coated capsules of omeprazole in healthy volunteers.

A comparative bioavailability study was carried out on two enteric-coated capsules (20 mg each) of omeprazole (omeprazole, Alembic: "A" and Losec, Astra, England: "B"). The in-vitro dissolution of both products "A" and "B" met the prescribed USP standard. The bioavailability of single dose (20 mg) and multiple doses (20 mg once daily for 7 days) of both products "A" and "B" were carried out in eight healthy male volunteers in a crossover design. The rate and extent of bioavailability of omeprazole was higher in product "A" following a single oral dose, suggesting its therapeutic advantage over the product "B" in the prevention of acid aspiration during surgery. In multiple dose study, the two products were found bioequivalent as assessed by AUC0-infinity, Cmax, tmax and t1/2 elimination.

Adult↗

Effect of peripheral administration of cinnarizine and verapamil on the abstinence syndrome in diazepam-dependent rats.

The effects of two calcium channel blockers (verapamil and cinnarizine) were evaluated on diazepam withdrawal symptoms. Rats were made diazepam dependent by chronic treatment with daily injections of the drug, 20 mg/kg IP for 3 weeks. On abrupt termination of the drug, animals showed withdrawal hyperactivity that was assessed by autonomic, behavioural and motor signs. The peak effect was seen 3 days after the withdrawal of diazepam. On IP administration, verapamil and cinnarizine (10, 20 and 40 mg/kg) given on eight occasions at an interval of 12 h reversed the withdrawal-induced increase in spontaneous motor activity. Cinnarizine in higher doses (20 and 40 mg/kg) was found to be effective in suppressing the behavioural signs but verapamil did not show any protective effect against startle response and irritability. These results suggest that modulation of the calcium influx in the CNS might influence withdrawal.

Animals↗

Development of antiviral treatment strategies in murine models.

Murine models with type C murine leukemia viruses have been used to develop major new prophylactic and therapeutic strategies in vaccination, drug therapy of acute virus exposure and chronic viremia, combination therapy, prevention of maternal transmission, and therapy targeted to the central nervous system. Transgenic mice expressing either the whole human immunodeficiency virus type 1 (HIV-1) provirus or subgenomic sequences allow the in vivo analysis of selected HIV-1 functions. The full replicative cycle of HIV-1 can be studied in human/mouse chimerae which were created by transplanting human hematolymphoid cells into SCID mice. The chimeric SCID mouse models have been used successfully to evaluate anti-HIV-1 drugs. The role of the various murine retrovirus systems in the development of anti-HIV-1 and anti-AIDS therapies is summarized.

Animals↗

MK-801 antagonizes the lethal action of centrally and peripherally administered cypermethrin in mice and rats.

The present study investigated the effect of MK-801, an N-methyl-D-aspartate antagonist, on the convulsant lethal action of cypermethrin administered centrally or peripherally. Cypermethrin produced severe convulsions and death in a dose-dependent manner. MK-801 (0.5, 1 and 2 mg kg-1, intraperitoneally) significantly increased the onset time of convulsions and decreased the mortality in the peripherally treated cypermethrin group. MK-801 (1.0 and 2.0 mg kg-1) attenuated the convulsant action of cypermethrin (50 micrograms, intracerebroventricularly) significantly. Survival rate was also increased significantly. However, MK-801 (0.5 mg kg-1) did not produce any significant protective effect against centrally administered cypermethrin. These results suggest excitatory amino acids to be a target for pyrethroid-induced neurotoxicity.

Animals↗

Drug interaction between rifampicin, isoniazid and cotrimoxazole in rabbits.

1 The results of cotrimoxazole (CTZ) co-administration (15 mg kg-1 trimethoprim + 40 mg kg-1 sulphamethoxazole) on plasma concentration and various pharmacokinetic parameters of rifampicin (RIF, 24 mg kg-1) and isoniazid (INH, 14 mg kg-1) were studied. 2 In the test group (n = 6), CTZ was administered on the 24th day of antitubercular treatment (ATT) and given for 7 d. 3 At the end of concurrent treatment with CTZ, RIF half-life (t1/2) and plasma concentration were both increased. However, there was no effect on INH half-life and plasma concentration.

Animals↗

A preliminary study on the interaction between ethanol and propranolol in normal human subjects.

Ethanol significantly increased the steady-state peak concentration of propranolol while propranolol significantly reduced the total body clearance of ethanol in healthy human volunteers. Ethanol per se caused tachycardia and rise in systolic blood pressure while propranolol administration resulted in bradycardia. In combinations, ethanol and propranolol caused significant fall in diastolic blood pressure without any significant changes in the heart rate and systolic blood pressure compared to the control readings of four healthy male volunteers. The kinetic and haemodynamic interactions observed between ethanol and propranolol in the preliminary study are of clinical relevance and need further exploration.

Adult↗

Memory enhancing effects of granisetron (BRL 43694) in a passive avoidance task.

Recent evidence suggests that serotonin plays an important role in learning and memory processes in animals. The present study examined the effect of the 5-HT3 receptor antagonist, granisetron (BRL 43694), on acquisition, retention and retrieval of a passive avoidance response in mice. Granisetron (1 and 10 micrograms/kg) administered 30 min before presentation of footshock increased the step-down latency when tested 24 h after footshock. The acquisition process was not affected by a dose of 100 micrograms/kg. Granisetron (10 and 100 micrograms/kg) produced a significant increase in latency to step out of the safety zone, when administered immediately after or 23.5 h after footshock. However, at 1 microgram/kg, granisetron had no effect. These results confirm the important role played by 5-HT in the process of learning and memory, and also suggest that memory enhancement may be possible with non-cholinergic treatments.

Animals↗

Diazepam-atenolol combination antagonizes aminophylline-induced convulsions and lethality in mice.

The present study was undertaken to identify protective drugs against aminophylline (240 mg/kg i.p.)-induced convulsions and lethality in mice. Diazepam (10 mg/kg) and valproic acid significantly prevented the convulsions, but were not effective in preventing mortality. Phenytoin, atropine, carbamazepine and atenolol were ineffective in protecting against convulsions and death. Ketamine gave partial protection against convulsions, but was not effective in preventing mortality. Diazepam (10 mg/kg) and atenolol (5 mg/kg) administered together gave total protection against convulsions and death. These results show that aminophylline-induced convulsions are relatively resistant to antiepileptic drugs, and that a combination of diazepam and a beta-blocker (atenolol) has potential as an anti-aminophylline agent.

Aminophylline↗

Post-coital antifertility action of Ruta graveolens in female rats and hamsters.

Different preparations of Ruta graveolens were administered orally to female rats (Days 1-10 post coition) and female hamsters (Days 1-6 post coition). The powdered root (CDR), aerial parts (CDA) and the aerial parts aqueous extract (AEA) all showed potential anticonceptive activity in rats. Limited administration on selected days of CDA showed uniformly lesser activity than with 10-day treatment. Sequentially prepared petroleum ether and methanol extracts of CDA were as active as CDA itself. The benzene and chloroform extracts were toxic and inactive. Rutin, a known chemical constituent of the plant, was found to be inactive. None of the above preparations showed activity in hamsters.

Animals↗

Effects of morphine on memory: interactions with naloxone, propranolol and haloperidol.

The effects of morphine on memory have been shown to be dependent on the strain of animal used and on the experimental parameters. Memory was assessed in a passive avoidance task using Swiss albino (ICRC) mice. Morphine at doses of 1, 3 and 10 mg kg-1 was administered immediately after foot shock (memory retention) or 23.5 h after foot shock (memory retrieval). Retest step-down latencies measured 24 h later showed that morphine did not affect memory retention but dose-dependently impaired retrieval of memory. Administration of naloxone 0.1 mg kg-1 antagonised the effects of morphine and impaired memory retention. Propranolol 0.3 mg kg-1 along with morphine 3 mg kg-1 impaired memory retention only while haloperidol 0.1 mg kg-1 improved the impairment of memory retrieval caused by morphine 3 mg kg-1. Glucose did not alter the effects of morphine on memory. There was no per se effect of morphine, naloxone, propranolol, glucose and haloperidol on memory at the doses used. The effect of morphine on memory retention is mediated by opioid mechanisms; however, adrenergic and dopaminergic mechanisms possibly modulate retention and retrieval of memory, respectively.

Animals↗

Controlled clinical trial of nifedipine alone and in combination with dilazep in patients with angina pectoris.

The present study was performed to see if the combined treatment with nifedipine and dilazep offers any advantage over monotherapy with nifedipine alone in angina of effort. Thirty-three patients out of 40 with classical stable angina of effort completed this double-blind, randomized, parallel design comparative clinical trial. Both nifedipine alone (15-60 mg) and in combination with dilazep (50 mg) three times a day produced a significant reduction in angina attacks, consumption of nitroglycerin tablets and increased exercise tolerance. There was, however, no difference in the reduction in these parameters between the two groups. There was no significant reduction in blood pressure both systolic as well as diastolic and rate pressure product both when nifedipine was given alone and when it was given in combination with dilazep. Laboratory data did not reveal any dysfunction of liver, kidney and hemopoietic system. The results obtained show that there was no beneficial effect of adding dilazep to nifedipine therapy in the treatment of angina pectoris.

Angina Pectoris↗