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Biomedical subjects

S K Kulkarni

Publications and source records attributed to S K Kulkarni.

At least 73 records · Page 4Linked to original sources
PubMed2000

Melatonin reversal of lipopolysacharides-induced thermal and behavioral hyperalgesia in mice.

The perception of pain sensation (threshold), whether local or central, is altered by inflammatory processes. Anti-inflammatory drugs block this by raising the pain threshold and by reducing the inflammatory process. Melatonin is claimed to have anti-inflammatory activity in animal models of acute and chronic inflammation. However, it is not known whether melatonin can reverse the hyperalgesia that is secondary to the inflammation. The present study aimed to assess the modulatory effect of melatonin on lipopolysaccharides-induced alteration of pain perception in mice. Central perception of pain was assessed with the tail-flick and hot-plate methods and local hyperalgesia was assessed by noting the animal's reactions such as paw licking and rearing after the intraplantar injection of lipopolysaccharides (5 microg/paw). Local administration (intraplantar) of lipopolysacharides induced hyperalgesia when measured by both central effects and behavioral reactions. Melatonin (5 and 10 mg/kg), like dexamethasone (0.5 mg/kg), given 30 min prior to, and 4 and 8 h after lipopolysaccharides (5 microg/paw) challenge attenuated central and behavioural hyperalgesia. The attenuation of lipopolysaccharides-induced hyperalgesia by melatonin was not reversed by naltrexone (4 mg/kg). In vitro studies showed that melatonin, in concentrations ranging from 100 to 1000 nM, suppressed tumor necrosis factor-alpha (TNF-alpha) without affecting the nitric oxide (NO) release in lipopolysaccharides-activated murine peritoneal macrophages. Taken together, the present results demonstrated that melatonin reverses lipopolysaccharides-induced hyperalgesia.

Adjuvants, Immunologic↗
PubMed2000

Melatonin reversal of DOI-induced hypophagia in rats; possible mechanism by suppressing 5-HT(2A) receptor-mediated activation of HPA axis.

Serotonin type 2A (5-HT(2A)) receptor-mediated neurotransmitter is known to activate hypothalamic-pituitary-adrenal (HPA) axis, regulate sleep-awake cycle, induce anorexia and hyperthermia. Interaction between melatonin and 5-HT(2A) receptors in the regulation of the sleep-awake cycle and head-twitch response in rat have been reported. Previous studies have shown that melatonin has suppressant effect on HPA axis activation, decreases core body temperature and induces hyperphagia in animals. However, melatonin interaction with 5-HT(2A) receptors in mediation of these actions is not yet reported. We have studied the acute effect of melatonin and its antagonist, luzindole on centrally administered (+/-)-1-(2, 5-dimethoxy-4-iodophenyl) 2-amino propane (DOI; a 5-HT(2A/2C) agonist)-induced activation of HPA axis, hypophagia and hyperthermia in 24-h food-deprived rats. Like ritanserin [(1 mg/kg, i.p.) 5-HT(2A/2C) antagonist], peripherally administered melatonin (1.5 and 3 mg/kg, i.p.) did not affect the food intake, rectal temperature or basal adrenal ascorbic acid level. However, pretreatment of rats with it significantly reversed DOI (10 microgram, intraventricular)-induced anorexia and activation of HPA axis. But the hyperthermia induced by DOI was not sensitive to reversal by melatonin. Mel(1) receptor subtype antagonist luzindole (5 microgram, intraventricular) did not modulate the DOI effect but antagonized the melatonin (3 mg/kg, i.p.) reversal of 5-HT(2A) agonist response. The present data suggest that melatonin reversal of DOI-induced hypophagia could be due to suppression of 5-HT(2A) mediated activation of HPA axis.

Adrenal Glands↗
PubMed2000

Anti-depressant action of melatonin in chronic forced swimming-induced behavioral despair in mice, role of peripheral benzodiazepine receptor modulation.

The possible antidepressant effect of physiological and pharmacological doses of melatonin was investigated in the Porsolt forced swimming-induced behavioral despair test. The duration of immobility period of BALB/c and C57BL/6J mice during a 6-min swim test was measured at noon (11:00-12:00 h), early dark (20:00-21:00 h) and at midnight (1:00-2:00 h), respectively. The circadian time cycle did not alter the duration of immobility in either strains of mice. Similarly, exogenously administered melatonin (10-1000 microg/kg congruent with 50 nM to 5 microM/mouse), a dose that could act on high affinity melatonin receptors, did not modify the duration of immobility period at any of the time intervals studied in either strains of the mice. This suggested that neither circadian variation influenced the duration of immobility period of BALB/c and C57BL/6J mice nor at physiological doses melatonin showed any anti-depressant action. Acute administration of higher doses of melatonin (2.5-10 mg/kg) failed to induce any anti-depressant activity in mice which were subjected to forced swimming test for the first time. However, daily administration of melatonin (2.5-10 mg/kg) prior to swimming test significantly reversed the increase in immobility period that was observed on chronic exposure to swimming test. This effect was comparable with the effect of GABA-benzodiazepine (BZ) receptor agonists. Similarly, like GABAergic drugs, acute administration of melatonin also showed anti-depressant activity in a mice which were exposed to chronic forced swimming test. The anti-depressant action of melatonin was sensitive to reversal by peripheral BZ receptor antagonist, PK11195. Whereas, flumazenil failed to reverse the anti-depressant action of melatonin, thereby suggesting that central BZ receptor were not involved in its action. In conclusion the study showed that at pharmacological doses melatonin has anti-depressant action in chronic forced swimming-induced despair behavior by an action involving peripheral BZ receptors.

Alprazolam↗
PubMed2000

The patellofemoral joint in total knee arthroplasty: is the design of the trochlea the critical factor?

The outcome at 10 years is reported of a prospective study of 2 cohorts of total knee arthroplasties treated with (center A) or without (center B) patellar replacement. The same tibiofemoral components were used in all knees. The cohorts were demographically similar. A total of 124 patellae were treated by replacement, and 143 were treated without replacement. The clinical outcome and the patellofemoral revision rates were the same in the 2 cohorts: 1 patient required analgesia for anterior knee pain after replacement, and 1 without replacement required patellar replacement for pain. In the replaced group, patellofemoral survival on a best-case scenario was 100% at 10 years; on a worst-case scenario, 96%. One of the unreplaced patellae had been resurfaced for pain by 10 years. In view of the satisfactory and similar outcomes with and without replacement, we suggest that an appropriate design for the prosthetic trochlea, rather than the replacement or otherwise of the patella, is the main determinant of patellofemoral outcome in total knee arthroplasty. Patella replacement may be optional. Desirable trochlea design features are described.

Adult↗
PubMed2000

Differential role of dopamine D1 and D2 receptors in isoniazid-induced vacuous chewing movements.

Tardive dyskinesia (TD) is a syndrome of potentially irreversible and involuntary hyperkinetic disorders that occurs during chronic neuroleptic therapy and is a major limitation of such therapy. Vacuous chewing movements (VCMs) in rats have been widely accepted as an animal model of tardive dyskinesia. In the present study isoniazid (1, 2 and 5 microM i.c.v.) dose-dependently produced VCMs in rats. The response produced by a 10-microM dose was lower than that of earlier doses but was statistically significant when compared to a saline-treated group. Diazepam (1 and 4 mg/kg i.p.) and progabide (50 and 100 mg/kg i.p.) dose-dependently reversed the isoniazid-induced VCMs. Haloperidol (0.5 and 1 mg/kg i.p.) and SCH-23390 (0.25 and 0.5 mg/kg i.p.) reversed the isoniazid-induced VCMs in a dose-dependent manner. Sulpiride (25 and 50 mg/kg i.p.), a dopamine D2 receptor antagonist, had no effect on isoniazid-induced VCMs. SKF-38393 (10 and 15 mg/kg i.p.) dose-dependently augmented the isoniazid-induced VCMs. Quinpirole 0.02 mg/kg i.p. had no effect on isoniazid-induced VCMs but a higher quinpirole dose (0.05 mg/kg) significantly reduced isoniazid-induced VCMs. Isoniazid (2 microM i.c.v.) produced stereotypy (grooming and rearing) in rats. Haloperidol (0.5 and 1 mg/kg i.p.), SCH-23390 (0.25 and 0.5 mg/kg i.p.) and sulpiride (25 and 50 mg/kg i.p.) decreased the severity of isoniazid-induced stereotypy. SKF-38393 (10 and 15 mg/kg i.p.) dose-dependently augmented the isoniazid-induced grooming behavior more prominently as compared to quinpirole (0.02 and 0.05 mg/kg i.p.); on the other hand quinpirole potentiated isoniazid-induced rearing behavior. In conclusion, the results of the present study demonstrated the differential involvement of dopamine D1 and D2 receptors in isoniazid-induced VCMs.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed2000

Cyclooxygenase isoenzymes and newer therapeutic potential for selective COX-2 inhibitors.

Cyclooxygenase (COX), also known as prostaglandin G/H synthase, is a membrane-bound enzyme responsible for the oxidation of arachidonic acid to prostaglandins that was first identified over 20 years ago. In the past decade, however, more progress has been made in understanding the role of cyclooxygenase enzymes in various pathophysiological conditions. Two cyclooxygenase isoforms have been identified and are referred to as COX-1 and COX-2. COX-1 enzyme is constitutively expressed and regulates a number of housekeeping functions such as vascular hemostasis and gastroprotection, whereas COX-2 is inducible (i.e., sites of inflammation) by number of mediators such as growth factors, cytokines and endotoxins. Nonsteroidal antiinflammatory drugs (NSAIDs) produce their therapeutic effects through inhibition of COX, the enzyme that makes prostaglandins. Nonselective inhibition of COX isoenzyme leads to not only beneficial therapeutic effects but also a number of detrimental effects. Beneficial effects are due to inhibition of COX-2 and detrimental effects are due to inhibition of physiological COX-1. The present review discusses the biology as well as the role of these COX isoenzymes in various pathophysiological conditions.

Animals↗
PubMed2000

AT1 receptor antagonism enhances angiotensin-II-facilitated carrageenan-induced paw edema.

Recent studies have demonstrated that the renin-angiotensin system (RAS) participates in the processes of inflammation. An active component of this system, angiotensin II (Ang II), differentially regulates the production of oxyradicals, nitric oxide, prostaglandins, platelet-activating factors and bradykinins by acting through AT1 or AT2 receptor subtypes. Many of the physiological actions of Ang II mediated through AT1 and AT2 receptors are opposite and thereby show physiological antagonism to each other. In the present study, we evaluated the effect of locally administered Ang II, the ACE inhibitor captopril and the AT1 receptor antagonist losartan in the carrageenan model of acute inflammation. Local administration of losartan (10-50 micrograms/paw) or Ang II (0.2-1 microgram/paw) alone did not induce inflammation, but significantly enhanced the carrageenan-induced edema in a dose-dependent manner. Coadministration of subeffective doses of losartan (10 micrograms/paw) and Ang II (0.2 microgram/paw) significantly potentiated the carrageenan-induced inflammation. In conclusion, the present study predicts that Ang II might be formed locally during carrageenan-induced acute inflammation. Potentiation of the Ang II effect in carrageenan-induced inflammation by losartan may be mediated through over-stimulation of unblocked AT2 receptors or due to stimulation of inflammatory pathways by unknown mechanisms.

Angiotensin II↗
PubMed2000

Differential effect of a polyherbal formulation-OB-200G in male and female mice subjected to forced swim stress.

The antistress effect of a polyherbal formulation-OB-200G (500 mg/kg. p.o.) was studied in both male and female mice subjected to forced swim stress. Fluoxetine (10 mg/kg, i.p.) was chosen as standard drug for comparison. Exposure of mice to chronic stress regime resulted in decreased body weight in both male and female mice, increased sweetened food intake, anxiety, depression and locomotor activity in stressed female mice as compared to unstressed control (normal) mice. Treatment with OB-200G resulted in a further decrease in body weight, increased food intake and locomotor activity in both stressed male and female mice. It also reduced immobility time, decreased latency to enter and increased number of entries and time spent in mirror chamber in stressed female mice. Administration of fluoxetine (10 mg/kg, i.p.) decreased body weight and food intake in both stressed male and female mice. Fluoxetine treatment also increased time spent in mirror chamber and decreased immobility time in stressed female mice. Thus, like fluoxetine, OB-200G decreased body weight and produced antianxiety and antidepressant effects in stressed female mice and may prove beneficial in obese patients reported to be more susceptible to stress-related psychological disorders.

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

Studies on anticonvulsant actions of L-deprenyl.

L-Deprenyl (Selegeline) introduced for use in parkinson's disease, is implicated to show beneficial effects in epilepsy, alzheimer's disease, cognition, depression and other age related neurological diseases. In this study, we investigated the CNS effects of L-deprenyl with special reference to epilepsy, anxiety and cognition and memory in mice. L-deprenyl (10, 20 and 40 mg/kg) showed a significant anticonvulsant activity against pentylenetetrazole (PTZ)-induced convulsions. Combination of L-deprenyl (10 mg/kg) with the sub-protective dose of diazepam (1 mg/kg) showed potentiation of the anticonvulsant effect. In the maximal-electroshock (MES)-induced convulsions, L-deprenyl (10 mg/kg) significantly delayed the onset and decreased the duration of extensor phase. Its combination with the lower dose of phenytoin (10 mg/kg) showed potentiation in response compared to the per se effect of both the drugs. However, L-deprenyl did not show any protective effect in lithium-pilocarpine induced status epilepticus. Acute treatment with L-deprenyl had no effect on learning and memory. In chronic treatment, L-deprenyl per se showed no effect on learning and memory but did improve the condition in mice with scopolamine induced memory deficit. L-Deprenyl per se was anxiogenic though in combination with diazepam (1 mg/kg) it potentiated the antianxiety effect of the latter. The above observations suggest that in epilepsy, L-deprenyl might be acting partially by influencing the GABAA/benzodiazepine mechanism in the brain (similar to diazepam and phenytoin), and in cognition enhancing effect, the cholinergic system might be playing a role. Thus, L-deprenyl could prove to be an adjuvant in the antiepileptic therapy and beneficial in dementia associated with epilepsy.

Animals↗
PubMed2000

Motor and electrographic response of refractory experimental status epilepticus in rats and effect of calcium channel blockers.

Effects of various calcium channel inhibitors have been studied in lithium-pilocarpine model of status epilepticus. Status epilepticus was induced by administration of lithium chloride (3 meq/kg) followed 21 hr later by pilocarpine (30 mg/kg). Diltiazem (5 and 10 mg/kg) was not effective in delaying onset of convulsions. Verapamil (20 mg/kg) showed protection against lithium-pilocarpine-induced convulsions. The dihydropyridine nifidepine (2.5 and 5 mg/kg) did not show any protection in this model. Amlodipine (5 and 10 mg/kg) as partially protective. Flunarizine (10 and 20 mg/kg) delayed the onset of forelimb clonus and rearing and only 60% of the rats underwent status in the 20 mg/kg group. Pre-treatment of MK-801 led to a potentiation of the antiseizure activity of calcium channel inhibitors. The percent increase in amplitude at various time points with amlodipine pretreatment was significant only at the 30th min recording, and at the rest of the time frames was practically similar as the controls. It can be concluded that the anticonvulsant action of MK-801 can be enhanced by centrally acting calcium channel inhibitors.

Animals↗
PubMed2000

Analgesic and anti-inflammatory effects of phosphodiesterase inhibitors.

The aim of the present study was to investigate the role of phosphodiesterase (PDE) enzyme inhibitors namely rolipram and theophylline in pain and inflammation in experimental animals. Rolipram, a selective PDE IV inhibitor and theophylline a nonspecific PDE inhibitor exerted dose dependent analgesic and anti-inflammatory effect against acetic acid-induced writhing in mice and carrageenan-induced paw edema in rats, respectively. Nimesulide (1, 2 mg/kg) produced significant anti-inflammatory effect. Further, nimesulide (0.5 mg/kg) potentiated analgesic effect of rolipram but it failed to modulate the anti-inflammatory effect of PDE inhibitors. Present study suggests that PDE enzymes might be playing a role in nociceptive and inflammatory responses in animals.

Abdominal Pain↗
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

Antinociceptive and anti-inflammatory effects of Tanacetum parthenium L. extract in mice and rats.

Oral administration of the feverfew (Tanacetum parthenium) extract led to significant antinociceptive and anti-inflammatory effects against acetic acid-induced writhing in mice and carrageenan-induced paw edema in rats, respectively. These responses were dose-dependent (10, 20, 40 mg/kg, p.o.). Parthenolide (1, 2 mg/kg i.p.), the active constituent of the extract also produced antinociceptive and anti-inflammatory effects. Naloxone (1 mg/kg i.p.), an opiate antagonist, failed to reverse feverfew extract and parthenolide-induced antinociception. Feverfew extract in higher doses (40, 60 mg/kg p.o.) neither altered the locomotor activity nor potentiated the pentobarbitone-induced sleep time in mice. It also did not change the rectal temperature in rats. Feverfew extract exerted antinociceptive and anti-inflammatory effects without altering the normal behaviour of the animals.

Acetic Acid↗
PubMed1999

Reversal of morphine tolerance and dependence by melatonin: possible role of central and peripheral benzodiazepine receptors.

Possible reversal by melatonin of morphine-induced tolerance and dependence was studied in mice. A 10-day repeated injection regimen was followed to induce morphine tolerance and dependence. Co-administration of melatonin (1-10 mg/kg, i.p.) with morphine (10 mg/kg, s.c.) during the induction phase (day 1 to 9) reversed the development of opioid tolerance and dependence tested on 10th day. On the other hand acute administration of melatonin (1-10 mg/kg) on the 10th day, ie. during the expression phase of morphine dependence, it reduced the incidence of naloxone-induced withdrawal jumps without affecting the tolerance to analgesic effect. Co-administration of flumazenil (2 mg/kg, i.p.), a central benzodiazepine (BZ) receptor antagonist had no effect on melatonin response, whereas peripheral antagonist for BZ receptor PK11195 (2 mg/kg, i.p.) significantly reversed the attenuating effect of melatonin on physical dependence both during induction and expression phase of morphine tolerance and dependence. These observations suggest that melatonin reverses development of tolerance and dependence to morphine, and this action possibly involved peripheral benzodiazepine receptors.

Analgesics, Opioid↗
PubMed1999

Effect of olanzapine on behavioural changes induced by FG 7142 and dizocilpine on active avoidance and plus maze tasks.

The present study examined the effect of atypical antipsychotic olanzapine on FG 7142- (N-methyl-beta-carboline-3-carboxamide) and dizocilpine-induced cognitive impairment in active avoidance paradigm and elevated plus maze in mice. Both FG 7142 (5 mg/kg) and dizocilpine (0.1 mg/kg) increased the latency to reach shock-free zone (SFZ) both during training and retention session in active avoidance paradigm. This effect was reversed by olanzapine (0.063, 0. 125, 0.25 and 0.5 mg/kg). Similarly, FG 7142 (5 mg/kg) increased transfer latency (TL) on both first and second day in elevated plus maze. The lower doses of olanzapine (0.063 and 0.125 mg/kg) reversed the effect of FG 7142 on second day in elevated plus maze but higher doses (0.25 and 0.5 mg/kg) failed to modify the effect of FG 7142 both on first and second day. Dizocilpine (0.1 mg/kg) treatment did not affect TL on first day while on second day, it increased TL significantly. Olanzapine (0.063 and 0.125 mg/kg) reversed the effect of dizocilpine on elevated plus maze but the higher doses (0. 25 and 0.5 mg/kg) failed to reverse it. Even though olanzapine (0. 063, 0.125 and 0.25 mg/kg) failed show any effect per se in active avoidance task, the higher dose (0.5 mg/kg) increased the latency to reach SFZ on second day. Olanzapine (0.063, 0.125, 0.25 and 0.5 mg/kg) did not show any per se effect on TL in elevated plus maze on first day while on second day, olanzapine (0.125, 0.25 and 0.5 mg/kg) increased TL as compared to control group. The present study demonstrated olanzapine's reversal of dizocilpine- and FG 7142-induced behavioural changes in active avoidance paradigm and elevated plus maze. Although the precise mechanism of action is unknown, olanzapine might be acting by blocking excessive dopaminergic activity in the prefrontal cortex.

Animals↗
PubMed1999

Preferential inhibition of dizocilpine-induced hyperlocomotion by olanzapine.

This study examined the putative inhibitory effect of the atypical antipsychotic, olanzapine, on dizocilpine (MK-801)-induced stereotypy and hyperlocomotion. Dizocilpine (0.1, 0.25 and 0.5 mg/kg) produced a dose-dependent increase in both stereotypy and hyperlocomotion. Pretreatment with olanzapine (0.25 and 0.5 mg/kg) inhibited the dizocilpine (0.5 mg/kg)-induced hyperlocomotion but not the stereotypy. At the higher doses (1, 2 and 4 mg/kg), olanzapine blocked both the stereotypy and hyperlocomotion induced by dizocilpine. Similarly, olanzapine, 0.25 and 0.5 mg/kg, did not inhibit apomorphine (3 mg/kg)-induced stereotypy, whereas the higher dose (1 mg/kg) blocked it. We also studied the effect of olanzapine on spontaneous locomotor activity and catalepsy. Olanzapine (0.25 and 0.5 mg/kg) did not induce a decrease in spontaneous locomotor activity but did so at the higher doses (1, 2 and 4 mg/kg). The lower doses (0.25, 0.5 and 1 mg/kg) did not induce catalepsy but higher doses (2 and 4 mg/kg) induced a significant catalepsy which lasted for more than 4 h. The results thus showed that, at lower doses, olanzapine selectively inhibited behaviours mediated by the mesolimbic/mesocortical system while at higher doses it inhibited behaviours mediated by both mesolimbic/mesocortical and nigrostriatal systems. Therefore, the minimal extrapyramidal side-effects produced by olanzapine at effective doses might be due to its preferential action at the mesolimbic/mesocortical area.

Animals↗