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Biomedical subjects

K Chopra

Publications and source records attributed to K Chopra.

At least 19 recordsLinked to original sources
PubMed2001

Comparative studies on the memory-enhancing actions of captopril and losartan in mice using inhibitory shock avoidance paradigm.

Renin angiotensin system (RAS) in the central nervous system participates in the processing of sensory information, learning and memory processes. Inhibitors of RAS, particularly angiotensin converting enzyme (ACE) inhibitors and angiotensin II (Ang II) receptor antagonists are reported to have potential nootropic effects in various learning and memory paradigms. The neurochemical basis underlying nootropic effect of ACE inhibitors are unclear due to wide range of substrate for this enzyme. In this study, we compared the effect of ACE inhibitor captopril and a selective AT(1)receptor antagonist losartan in a step-up shock avoidance (active avoidance) task. Captopril (5-10 mg/kg) but not losartan (5-10 mg/kg) improved learning in the second trial of the acquisition test. However, both these drugs were equally effective in enhancing retention of memory when administered prior to training. Retention enhancing effect of captopril and losartan were reversed by post-acquisition test administration of L-NAME (15 mg/kg), dizocilpine (0.05 mg/kg) and scopolamine (0.1 mg/kg). On the basis of above observations, it is concluded that decrease in endogenous Ang II activity in the brain might result in improved cognitive performance by enhancing cGMP pathways. However facilitation of acquisition only by captopril may be due to other putative mechanisms.

Angiotensin Receptor Antagonists↗
PubMed2001

Quercetin, a bioflavonoid, protects against oxidative stress-related renal dysfunction by cyclosporine in rats.

Nephrotoxicity is the most common and clinically important side effect of cyclosporine (CsA). Recent evidence suggests that reactive oxygen species (ROS) play an important role in CsA nephrotoxicity. This study was designed to demonstrate the role of oxidative stress and its relation to renal dysfunction and to investigate the effects of quercetin, a bioflavonoid with antioxidant properties, in CsA-induced nephrotoxicity. Quercetin (0.5 and 2.0 mg/kg i.p.) was administered 24 h before and concurrently with CsA (20 mg/kg s.c.) for 21 days. Tissue lipid peroxidation was measured as thiobarbituric acid reacting substances (TBARS). Renal function was assessed by estimating plasma creatinine, blood urea nitrogen (BUN), creatinine and urea clearance. Renal morphological alterations were assessed histopathologically. Pretreatment with CsA (20 mg/kg s.c.) for 21 days produced elevated levels of TBARS and deteriorated renal function as assessed by increased plasma creatinine, BUN and decreased creatinine and urea clearance as compared to vehicle-treated rats. The kidneys of CsA-treated rats showed severe striped interstitial fibrosis, arteriopathy, glomerular basement thickening, tubular vacuolization and hyaline casts. Quercetin (2 mg/kg) markedly reduced elevated levels of TBARS and significantly attenuated renal dysfunction and morphological changes in CsA-treated rats. It is likely that quercetin, due to its antioxidant properties, prevented CsA-induced ROS and consequently CsA nephrotoxicity. These results clearly demonstrate the pivotal role of oxidative stress and its relation to renal dysfunction, and also point to the therapeutic potential of the natural antioxidant quercetin in CsA-induced nephrotoxicity.

Animals↗
PubMed2000

Prooxidant role of histidine in hypoxic stressed mice and Fe(3+)-induced lipid peroxidation.

An attempt was made to study the effect of histidine on reactive oxygen species in a rodent model of hypoxic stress and in Fe(3+)-ascorbic acid-induced lipid peroxidation in mouse brain homogenates. The latency for onset of hypoxic stress-induced convulsions was decreased in histidine-treated animals with a concomitant rise in brain lipid peroxidation levels. In vitro, histidine potentiated Fe(3+)-ascorbic acid-induced lipid peroxidation in mouse brain homogenates while other antioxidants like B-HT and U-74500A inhibited the same. Moreover, Fe(3+)-histidine-induced lipid peroxidation could not be inhibited by preincubation of the system with high concentrations of ascorbic acid. Thus, it is concluded that histidine acts as a strong prooxidant potentiating the genesis of reactive oxygen species during hypoxic stress as well as during Fe(3+)-ascorbic acid-induced lipid peroxidation.

Animals↗
PubMed2000

Modulation of motor functions involving central dopaminergic system by L-histidine.

There exists a possibility of interactions of histaminergic system with other neurotransmitters and their receptors in the central nervous system. Experimental evidences suggest a possible inhibitory influence of histaminergic system on the dopaminergic system. To elucidate the possible interaction between the histaminergic and dopaminergic pathways, we devised a strategy to study their effects on locomotor function and stereotypy behaviour. We investigated the effect of L-histidine, the precursor of histamine, on apomorphine-induced stereotypy and perphenazine-induced catalepsy. Histidine antagonised apomorphine-induced stereotypy. This inhibitory effect of histidine was abolished by both H1- and H2-receptor antagonists, chlorpheniramine and cimetidine, respectively. Perphenazine-induced catalepsy was potentiated by histidine and this effect was inhibited by chlorpheniramine alone but not by cimetidine. These results confirm a possible histamine-dopamine interaction in the modulation of motor functions by the central nervous system.

Animals↗
PubMed1999

Brain renin angiotensin system (RAS) in stress-induced analgesia and impaired retention.

Physiological stress is known to produce analgesia and memory disruption. Brain renin angiotensin system (RAS) has been reported to participate in stress response and plays a role in the processing of sensory information. Angiotensin receptors (AT), particularly AT1 subtypes have been reported to be distributed in brain areas that are intimately associated with stress response. The purpose of present study was to examine the modulation of AT1 receptor in the immobilization stress and angiotensin II (AngII)-induced analgesia and impaired retention, and to determine whether resultant behavioral changes involve common sensory signals. Result of present experiments showed that immobilization stress in mice and rats, and intracerebroventricular (ICV) administration of AngII (10 and 20 ng) in rats produced an increase in tail-flick latency. Similarly, post training administration of AngII or immobilization stress produced impairment of retention tested on plus-maze learning and on passive avoidance step-down task. Both these responses were sensitive to reversal by prior treatment with losartan (10 and 20 mg/kg), an AT1 AngII receptor antagonist. On the other hand, naloxone, an opiate antagonist preferentially attenuated the stress and AngII-induced analgesia and retention deficit induced by immobilization stress, but failed to reverse the AngII induced retention deficit. These results suggest immobilization stress-induced analgesia and impaired retention involves the participation of brain RAS. Further, failure of naloxone to reverse AngII-induced retention impairment shows. AngII-induced behavioral changes are under control of different sensory inputs.

Angiotensin II↗
PubMed1999

Pharmacokinetics of pyrazinamide in children suffering from pulmonary tuberculosis.

SETTING: The Paediatric and Clinical Pharmacology unit of Maulana Azad Medical College and Associated Lok Nayak Hospital, New Delhi, India. OBJECTIVE: The pharmacokinetics of the anti-tuberculosis drug pyrazinamide was evaluated in 10 children aged 6 to 12 years suffering from pulmonary tuberculosis. METHODS: Serial blood samples were collected at 0, 1, 2, 4, 6, 12 and 24 hours after administration of pyrazinamide in a dose of 35 mg/kg. Serum pyrazinamide levels were analysed by spectrophotometry. RESULTS: The serum concentrations of pyrazinamide were above the minimum inhibitory concentration of 20 microg/ml of pyrazinamide for Mycobacterium tuberculosis up to 6 hours after drug administration in all the patients, and up to 12 hours in six patients. The mean peak serum concentration of pyrazinamide was 41.2+/-11.8 microg/ml, and this was attained in (Tmax) 2.9+/-1.7 hours. The elimination half life was 10.9+/-4.5 hours, the volume of distribution 16.1+/-10.9 litres and clearance 20.2+/-16.3 ml/minute. The corresponding mean residence time was 19.9+/-14.6 hours. CONCLUSION: The serum pyrazinamide concentrations achieved with a dose of 35 mg/kg were above the minimum inhibitory concentration of pyrazinamide for M. tuberculosis for over 6 hours after drug administration. It appears that the absorption and the clearance of pyrazinamide is slower, the elimination half life longer and the volume of distribution higher in children compared with the reported values in the adult population.

Antitubercular Agents↗
PubMed1999

Herpes gestationis in a mother and child.

Herpes gestationis (pemphigoid gestationis) is a rare autoimmune disease that appears during pregnancy or in the immediate postpartum period. We report the cases of a mother and neonate with immunofluorescence confirmed herpes gestationis both of whom had extensive cutaneous involvement.

Autoimmune Diseases↗
PubMed1998

Modulation of motor functions involving the dopaminergic system by AT1 receptor antagonist, losartan.

Growing evidence has indicated the existence of a brain renin angiotensin system and its possible interaction with other putative neurotransmitters and their receptors. In the present study, the effect of losartan, an AT1 receptor antagonist, was studied on the motor functions involving the dopaminergic system. Losartan (5-30 mg/kg) per se decreased locomotor activity without producing motor toxicity. It partially reversed the apomorphine-induced hyperlocomotion and stereotypy in mice, and potentiated neuroleptic-induced catalepsy in rats. On chronic administration (once daily for 21 days) losartan failed to block apomorphine-induced hyperlocomotion, but the inhibition of stereotypic response and potentiation of neuroleptic-induced catalepsy remained unaltered. These observations suggest that losartan inhibited the release of dopamine through AT1 receptor and also suggest the existence of a compensatory mechanism in certain brain region concerned with dopamine motor function.

Angiotensin Receptor Antagonists↗
PubMed1998

Involvement of cholinergic system in losartan-induced facilitation of spatial and short-term working memory.

In the present study we have shown the potential memory enhancing property of losartan, a selective Ang II AT1 receptor antagonist. Nootropic activity of losartan in mice was assessed by using passive avoidance step-down task and elevated plus-maze as a measure of short-term working and spatial memory respectively. Losartan at higher dose (10 mg/kg i.p) improved the basal performance in retention testing in both the test paradigms. Prior administration of losartan also attenuated retention deficit induced by scopolamine (0.3 mg/kg i.p). Moreover, physostigmine (0.05 mg/kg i.p) potentiated memory enhancing properties of losartan administered at lower dose (5 mg/kg i.p). On the basis of above observations it is concluded that the memory enhancing properties of losartan can be attributed to increased cholinergic activity.

Angiotensin Receptor Antagonists↗
PubMed1996

Pharmacokinetics of isoniazid in pulmonary tuberculosis--a comparative study at two dose levels.

OBJECTIVES: To compare the pharmacokinetic parameters and the clinical efficacy of isoniazid, administered in 10 mg/kg or 5 mg/kg to children suffering from pulmonary tuberculosis. DESIGN: A randomized, open, controlled clinical trial. SETTING: Teaching hospital in New Delhi. SUBJECTS: Twenty children suffering from pulmonary tuberculosis in the age group 6-12 years. INTERVENTIONS: A three drug antitubercular regimen comprising of rifampicin (10 mg/kg), pyrazinamide (30 mg/kg) and isoniazid in a dose of either 10 mg/kg (Group I) or 5 mg/kg (Group II) was administered for fourteen days. On day fifteen serial blood samples were collected at 0,1,2,3,6 and 24 h of isoniazid administration and analyzed spectrofluorometrically. MAIN OUTCOME MEASURES: Serum isoniazid concentrations and clinical response in both the groups. RESULTS: In both the groups, serum concentration of isoniazid were above the therapeutic range (0.5-2 micrograms/ml) at 6 h following drug administration. The minimum serum concentration of isoniazid was within or above minimum inhibitory concentration of the drug at 24 h in both the groups. The time to achieve maximum serum concentration, elimination half life, elimination rate constant, mean residence time, volume of distribution at steady state and plasma drug clearance were also comparable. At the end of 6 months follow up, all children showed comparable clinical and radiological improvement. CONCLUSION: Isoniazid in a dose of 5 mg/kg administered with other antitubercular drugs appears adequate for treatment of pulmonary tuberculosis in children.

Antibiotics, Antitubercular↗
PubMed1996

Comparative antioxidant effects of beta-adrenoceptor blockers, calcium antagonists and U-74500A against iron-dependent lipid peroxidation in murine ventricular microsomal membranes.

Recently we have shown that ACE inhibitors and platelet activating factor antagonists inhibit iron-dependent lipid peroxidation in murine ventricular membranes and possess beneficial effects on ischemia and ischemia reperfusion-induced myocardial injury, which has been ascribed to their capacity to scavenge or impair oxygen free radical generation. In the present study we investigated the effects of beta-adrenoceptor blockers and calcium antagonists on iron-dependent lipid peroxidation (LPO) in murine ventricular membranes and compared them with the lazaroid U-74500A, a potent antioxidant. Fe(2+)-vitamin C induced LPO in a concentration- and time-dependent manner, measured as thiobarbituric acid reactive substances (TBARS) formation. Pretreatment of ventricular membranes with gallopamil, verapamil, propranolol and metaprolol at concentrations of 5 microM and higher inhibited Fe(2+)-vitamin C-induced LPO in a concentration-dependent manner with IC50 values of 192.8-208.3 microM; however, they were less potent than U-74500A (IC50 6.8 microM). In contrast, atenolol, timolol, diltiazem and nifedipine inhibited LPO at very high concentrations with IC50 values of 864.5-971.5 microM. Inhibition of LPO may not be due to the drugs' classical pharmacological actions, but rather to their characteristic chemical structures or physicochemical interactions with biological membranes. In view of the pathological importance of LPO in cardiac ischemic injury, inhibition of LPO by gallopamil, verapamil, propranolol and metaprolol may provide additional cardioprotective activity and thus reinforces their beneficial effects in the treatment of ischemic heart disease.

Adrenergic beta-Antagonists↗
PubMed1995

Association of gastroesophageal reflux (GER) with bronchial asthma.

Eighty children with bronchial asthma and ten control cases underwent radionuclide gastroesophagography for the detection of gastroesophageal reflux. Thirty nine per cent asthmatic children demonstrated esophageal reflux on scintiscanning. The ten control subjects had no reflux. The presence of reflux correlated strongly with the presence of nocturnal exacerbation of symptoms. Bronchodilator therapy did not affect the prevalence of GER in asthmatic children.

Asthma↗