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Biomedical subjects

S K Kulkarni

Publications and source records attributed to S K Kulkarni.

At least 37 records · Page 2Linked to original sources

Structural and optical investigations of SiO2-CdS core-shell particles.

Cadmium sulfide nanoparticles (approximately 5 nm), chemically capped using thioglycerol molecules, have been anchored onto silica particles (approximately 80 nm) functionalized with 3-aminopropyltrimethoxysilane. Transmission electron microscopy clearly showed that at a low concentration of cadmium sulfide, nanoparticles were discretely and more or less uniformly attached onto the silica particles. At a high concentration of cadmium sulfide nanoparticles, an approximately 6-nm-thick compact shell of cadmium sulfide was formed on the silica particles. In both cases the nanocrystalline nature of cadmium sulfide particles was preserved, as is evident from X-ray diffraction and optical absorption spectra.

Journal Article↗

Memory enhancing activity of Glycyrrhiza glabra in mice.

In the traditional system of medicine, the roots and rhizomes of Glycyrrhiza glabra (family: Leguminosae) have been employed clinically for centuries for their anti-inflammatory, antiulcer, expectorant, antimicrobial and anxiolytic activities. The present study was undertaken to investigate the effects of Glycyrrhiza glabra (popularly known as liquorice) on learning and memory in mice. Elevated plus-maze and passive avoidance paradigm were employed to test learning and memory. Three doses (75, 150 and 300 mg/kg p.o.) of aqueous extract of Glycyrrhiza glabra were administered for 7 successive days in separate groups of animals. The dose of 150 mg/kg of the aqueous extract of liquorice significantly improved learning and memory of mice. Furthermore, this dose significantly reversed the amnesia induced by diazepam (1 mg/kg i.p.) and scopolamine (0.4 mg/kg i.p.). Anti-inflammatory and antioxidant properties of liquorice may be contributing favorably to the memory enhancement effect. Since scopolamine-induced amnesia was reversed by liquorice, it is possible that the beneficial effect on learning and memory was due to facilitation of cholinergic-transmission in mouse brain. However, further studies are necessitated to identify the exact mechanism of action. In the present investigation, Glycyrrhiza glabra has shown promise as a memory enhancing agent in all the laboratory models employed.

Administration, Oral↗

Improvement of mouse memory by Myristica fragrans seeds.

Memory is one of the most complex functions of the brain and involves multiple neural pathways and neurotransmitter systems. The present study was undertaken to investigate the effect of Myristica fragrans (MF) seeds on learning and memory in mice. The n-hexane extract of MF was administered orally in three doses (5, 10, and 20 mg/kg p.o.) for 3 successive days to different groups of young and aged mice. The learning and memory parameters were assessed using elevated plus-maze and passive-avoidance apparatus. The effect of MF extract on scopolamine (0.4 mg/kg i.p.)- and diazepam (1 mg/kg i.p.)-induced impairment in learning and memory was also studied. MF extract at the lowest dose of 5 mg/kg p.o. administered for 3 successive days significantly improved learning and memory of young and aged mice. This extract also reversed scopolamine- and diazepam-induced impairment in learning and memory of young mice. MF extract enhanced learning and retention capacities of both young and aged mice. The exact mechanism of the memory-improving effect of MF extract was not explored in the present study. But, the observed memory-enhancing effect may be attributed to a variety of properties (individually or in combination) the plant is reported to possess, such as antioxidant, anti-inflammatory, or perhaps procholinergic activity.

Animals↗

Memory-strengthening activity of Glycyrrhiza glabra in exteroceptive and interoceptive behavioral models.

In the traditional system of medicine, the roots and rhizomes of Glycyrrhiza glabra have been employed clinically for centuries for their anti-inflammatory, anti-ulcer, expectorant, antimicrobial, and anxiolytic activities. The present study was undertaken to investigate the effects of G. glabra, popularly known as liquorice (Mulathi), on learning and memory. The elevated plus-maze and passive avoidance paradigm were employed to evaluate learning and memory parameters. Three doses (75, 150, and 300 mg/kg p.o.) of aqueous extract of G. glabra were administered for 7 successive days in separate groups of mice. The dose of 150 mg/kg of the aqueous extract of liquorice significantly improved learning and memory of mice. Furthermore, this dose reversed the amnesia induced by diazepam (1 mg/kg i.p.), scopolamine (0.4 mg/kg i.p.), and ethanol (1 g/kg i.p.). Anti-inflammatory and antioxidant properties of liquorice may be contributing favorably to the memory enhancement effect. Since scopolamine-induced amnesia was reversed by liquorice, it is possible that the beneficial effect on learning and memory may be because of facilitation of cholinergic transmission in brain. However, further studies are necessitated to identify the exact mechanism of action. In the present investigation, G. glabra has shown promise as a memory enhancer in both exteroceptive and interoceptive behavioral models of memory.

Administration, Oral↗

Phosphodiesterase 5 enzyme and its inhibitors: update on pharmacological and therapeutical aspects.

Cyclic nucleotides are important secondary messengers that control many physiologic processes, including smooth muscle contractility. Phosphodiesterases (PDEs) comprise of a superfamily of metallophosphydrolases that specifically cleave the 3',5'-cyclic phosphate moiety of cAMP and/or cGMP to produce the corresponding 5' nucleotide. Currently 21 PDE genes have been cloned and are classified into 11 families (1-11) according to their sequence of homology, biochemical and pharmacological properties. Phosphodiesterase type 5 (PDE5) is one of the members of the superfamily that specifically cleaves cyclic guanosine monophosphate (cGMP), a key intracellular secondary messenger. It is composed of 875 amino acids and was first identified in lungs, vascular and tracheal smooth muscle, and platelets. PDE5 is selectively inhibited by sildenafil, vardenafil and tadalafil, and less selectively by zaprinast and dipyridamole. PDE5 inhibitors have been reported to possess antiplatelet aggregation, weak cardiac inotropic effects and vascular relaxant properties. The tissue distribution of the PDE5 family is relatively restricted compared with other PDEs. Still, recent immunohistochemical and reverse transcriptase-polymerase chain reaction analysis have demonstrated the presence of anti-PDE5 antibodies and PDE5 transcripts in rat cerebellum, kidney, pancreas, aortic smooth muscle cells, heart, placenta, skeletal muscle, and, to a much lesser extent, in other regions of the brain, liver and lungs. Research in this field is intense, with a goal of identifying and developing new, selective PDE5 inhibitors that would be beneficial in a number of maladies, as well as angina, hypertension and erectile dysfunction (ED).

3',5'-Cyclic-GMP Phosphodiesterases↗

Quercetin, a bioflavonoid, reverses haloperidol-induced catalepsy.

Neuroleptics are extensively used in the treatment of schizophrenia and other affective disorders. Unfortunately their use is often associated with distressing side effects involving the extrapyramidal tract, such as Parkinsonism and tardive dyskinesia. Neuroleptic-induced catalepsy has long been used as a model for extrapyramidal side effects such as Parkinsonian-like bradykinesia associated with antipsychotic use in humans. In the present study, haloperidol (2 mg/kg i.p.) was administered to mice to induce catalepsy and cataleptic response was measured for the next 4 h at 1 h intervals. Haloperidol treatment in mice induced a strong cataleptic state within 1 h of injection, reaching a maximal plateau after 2 h and lasting for 4 h. Vehicle-treated animals did not display catalepsy as they remained less than 5 sec on the bar at each time point. Pretreatment with quercetin dose-dependently (25-100 mg/kg p.o.) reduced the catalepsy score in haloperidol-treated animals. A dose response study of quercetin showed a characteristic U-shaped response curve, with maximum suppression observed at a dose of 100 mg/kg. On increasing the dose of quercetin to 300 mg/kg, no statistically significant difference in catalepsy score was observed compared with the haloperidol-treated group. In conclusion, the findings of the present study strongly suggest that quercetin can be screened as a potential drug candidate or as an adjuvant for the treatment of neuroleptic-induced extrapyramidal side effects.

Animals↗

Protective effect of bupropion on morphine tolerance and dependence in mice.

Possible reversal of morphine-induced tolerance and dependence by bupropion was studied in mice. A 10-day repeated injection regimen was followed to induce morphine tolerance and dependence. Bupropion (2 and 5 mg/kg) per se, when chronically administered for 9 days, failed to produce any significant change in tail-flick latency compared with the control mice. Chronic administration of bupropion (2 or 5 mg/kg) during the induction phase (days 1-9) delayed the development of tolerance to the antinociceptive action of morphine and also reversed naloxone- (2 mg/kg) precipitated withdrawal jumps. On the other hand, acute administration of bupropion (2 or 5 mg/kg) on day 10, i.e., during the expression phase of morphine dependence, reduced the incidence of naloxone-precipitated withdrawal jumps without affecting tolerance to the analgesic effect. In conclusion, results of the present study suggest the potential use of bupropion in tolerance and dependence.

Analgesics, Opioid↗

Prescription monitoring of anti-hypertensive drug utilisation at the Panjab University Health Centre in India.

INTRODUCTION: The present pilot study was conducted in order to establish the drug-prescribing trend of anti-hypertensive agents at the Panjab University Health Centre in India. METHODS: A pilot study of six-month duration was conducted at the Panjab University Health Centre. The information was collected from the patients attending the outpatient department through a random sample method. World Health Organisation-based prescription-auditing proforma was used for data collection. RESULTS: This study revealed that most of the male patients were on monotherapy (60 percent). In the monotherapy category, four classes of drugs were used. These were calcium channel blockers (48.1 percent), beta-blockers (46.2 percent), ACE inhibitors (3.9 percent) and diuretics (1.9 percent). Among monotherapy drugs, calcium channel blockers were prescribed most whereas diuretics were least used. Among those who were treated with drug combinations, 92.1% received two drugs and 7.9 percent received three drugs. In combination therapy, a two-drug combination consisting of beta-blockers and calcium channel blockers was given to the majority of the patients. Overall, 57.8 percent patients were treated with a single anti-hypertensive drug and 42.2 percent were treated with anti-hypertensive drug combinations. CONCLUSION: The present study represents the current prescribing trend for anti-hypertensive agents and it highlights certain shortcomings in the existing prescribing practice. There is a considerable scope for improvement, particularly the under-utilisation of diuretics in the present prescribing pattern of anti-hypertensive drugs.

Antihypertensive Agents↗

On the sleep promoting effects of BR-16A: interaction with GABAergic modulators.

Pentobarbitone-induced hypnosis test was used as an animal model to explore the role of BR-16A, a polyherbal formulation in sleep. Pentobarbitone produces quick sleep latency (onset) and prolongation of total sleep time (duration). Sleep latency and total sleep time were used as a parameters for the evaluation. BR-16A potentiated the effect of triazolam (0.1 mg/kg, ip) and alprazolam (0.25 mg/kg, ip). Melatonin (5.0 mg/kg, ip) and zolpidem (0.5 mg/kg, ip) did not produce any significant effect on sleep parameters. However, alprazolam (0.25mg/kg, ip) potentiated the effect of BR-16A (100 mg/ kg, po) in higher dose only. Sleep promoting effect of BR-16A in combination with GABAergic drugs (triazolam and alprazolam,) suggested that these drugs have common mechanism in sleep promoting effect of pentobarbitone and could be used along with other GABAergic hypnotics for the treatment of insomnia. This may reduce the dose of the latter drug(s). BR-16A can be used for the treatment of sleep and sleep-related disorders.

Alprazolam↗

Fluoxetine suppresses morphine tolerance and dependence: modulation of NO-cGMP/DA/serotoninergic pathways.

Although the phenomenon of opioid tolerance and dependence has been widely investigated, neither opioid nor non-opioid mechanisms are completely understood. In view of the modulation of 5-HT transport into presynaptic terminals in the brain by nitric oxide (NO) via cGMP, and the existence of a tonic 5-HTergic inhibition of dopamine release, the present study investigated the effect of fluoxetine, a selective serotonin reuptake inhibitor, and NO modulators L-N(G)-nitroarginine methyl ester (L-NAME; NO synthase inhibitor) and L-Arginine (substrate for nitric oxide synthase) alone or in combination against morphine tolerance and dependence. Animals developed tolerance to the antinociceptive effect of morphine (10 mg/kg s.c. twice daily) on day 3 and the degree of tolerance was further enhanced on days 9 and 10. The development of tolerance to the antinociceptive effect of morphine was delayed by prior administration of fluoxetine (10 mg/kg i.p, twice daily for 9 days) and L-NAME (10 mg/kg i.p. twice daily for 9 days) alone or in combination. It was accentuated by L-Arginine (50 mg/kg i.p. twice daily for 9 days) alone or in combination with fluoxetine (10 mg/kg i.p. twice daily for 9 days). Similarly, fluoxetine (10 mg/kg i.p.) or L-NAME (10 mg/kg i.p.), when administered acutely on day 10, reversed morphine-induced tolerance. L-Arginine (50 mg/kg i.p.) however, when administered acutely on day 10, accentuated morphine tolerance. Fluoxetine (10 mg/kg i.p. twice daily for 9 days) suppressed the development of morphine dependence as assessed by naloxone (2 mg/kg i.p.)-precipitated withdrawal jumps. This suppression of dependence was potentiated by L-NAME (10 mg/kg i.p. twice daily for 9 days) and reversed by L-Arginine (50 mg/kg i.p. twice daily for 9 days), respectively. Acute administration of the respective drugs on day 10 modulated morphine dependence in a similar fashion. L-Arginine also reversed fluoxetine-induced weight loss in morphine-dependent animals. The present study demonstrated that fluoxetine suppressed the dependence and development of tolerance to the antinociceptive effect of morphine. Fluoxetine-induced suppression was potentiated by L-NAME and accentuated by L-Arginine. The results therefore suggest that a complex phenomenon such as morphine tolerance and dependence might involve close interplay of the NO-c GMP/5-HT/DA receptor system. To the best of the authors' knowledge, this is the first report to suggest targeting this cascade for amelioration of opioid tolerance and withdrawal syndrome.

Animals↗

Formation of Cu and Cu2O nanoparticles by variation of the surface ligand: preparation, structure, and insulating-to-metallic transition.

Copper and copper (I) oxide nanoparticles protected by self-assembled monolayers of thiol, carboxyl, and amine functionalities [X(CH(2))(n)-CH(3), where X can be -COOH, -NH(2), or -SH] have been prepared by the controlled reduction of aqueous copper salts using Brust synthesis. The optical absorption spectrum (lambda(max)=289 nm) is found to be invariant with the nature of the capping molecule while the particle shape and distribution are found to depend strongly on it. A comparison of the protection efficiency for different capping agents such as dodecanethiol (DDT), tridecylamine (TDA), and lauric acid (LA) suggests that although zerovalent Cu is initially formed for dodecanethiol, all other cases allow oxidation to Cu(2)O nanoparticles. Despite the variation in particle size and relative stability, nanoparticles have been found to form oxides after a few days, especially for the case of LA and TDA surface capping. For all the samples studied, the size has been found to be 4-8 nm by high-resolution transmission electron microscopy. The protective ability is found to be better for dodecanethiol SAM (similar to the case of Au and Ag nanoparticles), while the order of capping efficiency varies as Cu-DDT>Cu-TDA>Cu-LA. In the present study we also demonstrate a reversible metal-insulator transition (MIT) in capped nanoparticles of Cu using temperature-dependent electrical resistivity measurement. However, the LA-capped sample does not show any such transition, possibly due to the oxide formation.

Journal Article↗

Microbial synthesis of semiconductor CdS nanoparticles, their characterization, and their use in the fabrication of an ideal diode.

Cadmium sulfide nanoparticles were synthesized intracellularly by a Schizosaccharomyces pombe strain when challenged with 1 mM cadmium in solution. The nanoparticles, a known semiconducting material, exhibited an absorbance maximum at 305 nm. X-ray scattering data showed that the nanoparticles had a Wurtzite (Cd(16)S(20))-type hexagonal lattice structure and most of the nanoparicles were in the size range of 1-1.5 nm. The nanoparticles were used in the fabrication of a heterojunction with poly (p-phenylenevinylene). The diode exhibited approximately 75 mA/cm(2) current at 10 V when forward biased and the breakdown occurred at approximately 15 V in the reverse biased mode. These characteristics are considered ideal for a diode.

Cadmium Compounds↗

Energetics of nanocrystalline TiO2.

The energetics of the TiO(2) polymorphs (rutile, anatase, and brookite) were studied by high temperature oxide melt drop solution calorimetry. Relative to bulk rutile, bulk brookite is 0.71 +/- 0.38 kJ/mol (6) and bulk anatase is 2.61 +/- 0.41 kJ/mol higher in enthalpy. The surface enthalpies of rutile, brookite, and anatase are 2.2 +/- 0.2 J/m(2), 1.0 +/- 0.2 J/m(2), and 0.4 +/- 0.1 J/m(2), respectively. The closely balanced energetics directly confirm the crossover in stability of nanophase polymorphs inferred by Zhang and Banfield (7). An amorphous sample with surface area of 34,600 m(2)/mol is 24.25 +/- 0.88 kJ/mol higher in enthalpy than bulk rutile.

Journal Article↗

Histaminergic modulation of stress-induced analgesia and cognitive dysfunction.

Physiological stress is known to produce analgesia and memory disruption. A large body of evidence favors the nonopiate mediation of stress-induced analgesia. It is suggested that brain histamine mediates nonopiate analgesia and participates in learning and memory in rodents. Histamine is released during stress, although the nature of histaminergic involvement in stress response is not clearly defined. Therefore, we studied the effect of L-histidine and histamine-receptor antagonists on antinociception and impaired retention induced by immobilization stress. In the present study, immobilization stress produced a naloxone-resistant analgesia that was potentiated by L-histidine and antagonized by pretreatment with the histamine receptor antagonists chlorpheniramine and cimetidine. L-histidine attenuated the memory disruption induced by immobilization stress, which was significantly reversed by chlorpheniramine but not by cimetidine. Thus the involvement of the central histaminergic system, through histamine H1- and H2-receptors, may be speculated in analgesia and cognitive deficit induced by immobilization stress.

Analgesia↗

Role of adenosine in drug-induced catatonia in mice.

Parkinson's disease is one of the most common neurodegenerative disorders affecting large majority of population who are older than age of 65. Apart from dopamine, acetylcholine and glutamate, adenosinc has also been identified in the basal ganglia. Adenosine modulates the release of a variety of neurotransmitters including dopamine. In order to establish adenosine-dopamine interactions in drug-induced catatonia we studied the effect of adenosine in drug-induced catatonia in mice. In the present study adenosine dose dependently produced catatonia when assessed on rota-rod and bar tests in mice. Adenosine also potentiated the catatonic effect of perphenazine. L-dopa plus carbidopa or OR-486 (a potent centrally acting COMT inhibitor) completely reversed adenosine-induced catatonia. Since reversal by scopolamine of adenosine-induced catatonia was not to the same extent as with l-dopa and OR-486 it appears that catecholamines particularly dopamine rather than cholinergic modulation is more important in adenosine induced catatonia. The motor dysfunction (catatonia) could be easily assessed using rota-rod test apparatus in mice.

Adenosine↗

Possible involvement of prostaglandins in haloperidol-induced orofacial dyskinesia in rats.

Dopaminergic abnormality is one of the pathological mechanisms involved in the pathophysiology of tardive dyskinesia, a late complication of neuroleptic treatment. Prostaglandins modulate the dopamine release in the striatum, the principle area involved in the pathophysiology of tardive dyskinesia. Rats were chronically treated with haloperidol (HPD) (1.5 mg/kg) for a period of 21 days, to induce orofacial dyskinesia. Behavioural assessment of orofacial dyskinesia was done 24 h after the last dose of haloperidol. Catalepsy was induced in rats by acute treatment with haloperidol (1 mg/kg), and catalepsy was scored for the next 4 h. Chronic haloperidol treatment induced profound vacuous chewing movements in rats. Indomethacin, a nonselective cyclooxygenase inhibitor dose-dependently (5-20 mg/kg) suppressed the vacuous chewing movements count in haloperidol-treated animals. In conclusion, the results of the present study infer that prostaglandins might play a significant role in the haloperidol-induced vacuous chewing movements, and prostaglandin synthesis inhibitors can serve as novel drug candidates for the treatment of tardive dyskinesia.

Animals↗

On the antinociceptive effect of fluoxetine, a selective serotonin reuptake inhibitor.

Antidepressant drugs are reported to be used as co-analgesics in clinical management of migraine and neuropathic pain. The mechanism through which they alleviate pain remains unknown. The present study explores the possible mechanism of a selective serotonin reuptake inhibitor (SSRI) fluoxetine-induced antinociception in animals. Acetic acid-induced writhing, hot plate and tail-flick test were used to assess fluoxetine-induced antinociception. Fluoxetine (5-20 mg kg(-1), i.p.) produced a significant and dose-dependent antinociceptive effect against acetic acid-induced writhing in mice. Fluoxetine (20 mg kg(-1)) also exhibited antinociceptive effect in tail flick as well as hot plate assays. Further, i.c.v. administration of fluoxetine showed significant antinociception against writhing test in rats. However, fluoxetine (1 microg/10 microl/rat, i.c.v.) did not exhibit any antinociceptive effect in serotonin-depleted animals. Further, pindolol (10 mg kg(-1), i.p.) enhanced fluoxetine-induced antinociceptive effect. The antinociceptive effect of fluoxetine was sensitive to blockade by naloxone (5 mg kg(-1), i.p.) and naltrexone (5 mg kg(-1), i.p.). These data suggest that fluoxetine-induced antinociception involves both central opioid and the serotoninergic pathways.

Analgesics↗

Effect of 5-HT1A and 5-HT2A/2C receptor modulation on neuroleptic-induced vacuous chewing movements.

Tardive dyskinesia is a serious motor side effect of chronic neuroleptic therapy. Chronic treatment or rats with neuroleptics leads to the development of abnormal oral movements called vacuous chewing movements. Vacuous chewing movements in rats are widely accepted as an animal model of tardive dyskinesia. Atypical antipsychotics such as clozapine and rispiridone are associated with a lower incidence of extrapyramidal side effects and tardive dyskinesia. The present study was aimed to explore the role of 5-HT1A, 5-HT2A/2C receptors in the expression of neuroleptic-induced orofacial dyskinesia. In the present study rats were chronically (for 21 days) treated with haloperidol (1.5 mg/kg, i.p.) to elicit vacuous chewing movements. The neuroleptic-induced vacuous chewing movements, viz., vertical jaw movements, tongue protrusions and bursts of jaw tremors, were counted during a 5-min observation period. Acute treatment with 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), a 5-HT1A receptor agonist, dose-dependently (0.05, 0.1 and 0.2 mg/kg, i.p.) reduced the haloperidol-induced vacuous chewing movements and headshakes. Both acute and chronic administration of seganserin, ketanserin and ritanserin, 5-HT2A/2C receptor antagonists, also reduced haloperidol-induced vacuous chewing movements in a dose-dependent (0.05, 0.1 and 0.2 mg/kg, i.p.) manner. In acute studies a higher dose of ritanserin (1 mg/kg) but not ketanserin (1 mg/kg) increased vacuous chewing movements, whereas a higher dose of seganserin (1 mg/kg) did not have any effect on vacuous chewing movements. All the drugs reduced haloperidol-induced headshakes in a dose-dependent fashion. These findings indicate that the serotonergic system, and particularly 5-HT1A and 5-HT2A/2C receptors, may be involved in haloperidol-induced orofacial dyskinesia, and that 5-HT receptors may provide novel targets for the development of drugs that can be used to reverse or prevent the extrapyramidal side effects associated with long-term antipsychotic treatment.

Animals↗