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Biomedical subjects

S K Kulkarni

Publications and source records attributed to S K Kulkarni.

At least 19 recordsLinked to original sources

Resveratrol and curcumin suppress immune response through CD28/CTLA-4 and CD80 co-stimulatory pathway.

The role of resveratrol and curcumin is well documented in cancer, inflammation, diabetes and various other diseases. However, their immunosuppressive action on T cells, B cells and macrophages is not well documented. In the present study, we have ascertained the effect of resveratrol and curcumin on T and B cells and macrophages. The most striking findings were that both resveratrol and curcumin suppressed the activity of T and B cells and macrophages, as evidenced by significant inhibition in proliferation, antibody production and lymphokine secretion. Interestingly, curcumin imparted immunosuppression by mainly down-regulating the expression of CD28 and CD80 and up-regulating CTLA-4. Resveratrol also functioned by decreasing the expression of CD28 and CD80, as well as by augmenting the production of interleukin (IL)-10.

Animals↗

Antagonistic activity of ascorbic acid (vitamin C) on dopaminergic modulation: apomorphine-induced stereotypic behavior in mice.

Among the various neurotransmitter systems implicated in the mechanism of action of ascorbic acid (vitamin C), the relationship between the dopaminergic system and ascorbic acid is not particularly clear. Ascorbic acid is speculated to have an antagonistic effect on dopaminergic modulation. With this background in mind, in the present study we have seen the effect of ascorbic acid per se and in combination with typical and atypical antipsychotic agents against apomorphine-induced stereotypic behavior in mice. Male Laka mice weighing 20-25 g were used in the present study. Apomorphine-induced stereotypic behavior was used as an animal model. Various dopaminergic modulators were used. Ascorbic acid dose-dependently inhibited stereotypic behavior produced by apomorphine in mice. It potentiated the antipsychotic activity of haloperidol (0.1 mg/kg i.p.), a typical antipsychotic agent. When administered along with atypical antipsychotics, clozapine (1-2 mg/kg i.p.), sulpiride (10-20 mg/kg i.p.) and risperidone (0.0025 mg/kg i.p.), ascorbic acid also potentiated their activity. Also when given along with SCH-23390, a selective D(1) antagonist, an additive effect was observed. Ascorbic acid also inhibited the supersensitization response of apomorphine on reserpinization (2 mg/kg i.p.). Interestingly, at a lower dose (100 mg/kg i.p.), ascorbic acid potentiated the dopaminergic activity of apomorphine (0.5 mg/kg) and BHT-920 (0.25 mg/kg i.p.). However, when given concomitantly with SKF-38393, it failed to alter the response of SKF-38393. The data substantiate the hypothesis that ascorbic acid potentiated the activity of typical as well as atypical antipsychotics and that the effect of ascorbic acid on the dopaminergic system is markedly dose dependent; a low dose (100 mg/kg i.p.) potentiated the dopaminergic action while higher doses (400-1,600 mg/kg i.p.) blocked it.

Animals↗

Diffusion dynamics during the nucleation and growth of Ge/Si nanostructures on Si(111).

We report a low energy electron microscopy study of the relation between self-organized Ge/Si(111)nanostructures and their local environment. By comparison with Monte Carlo simulations, three-dimensional islands are shown to display a substantial tendency towards self-ordering. This tendency may result from the diffusive nature of the nucleation processes. The size of individual nanostructures does not significantly correlate with the distance between neighboring islands. Thus energetic factors are thought to govern the competition among coexisting nanostructures to capture the deposited mass.

Journal Article↗

Protective effect of BR-16A, a polyherbal preparation against social isolation stress: possible GABAergic mechanism.

The antistress effects of BR-16A, a polyherbal preparation and its interaction with GABAergic modulators against social isolation-induced stress were investigated in the present study. Isolation stress was induced by keeping the mice (Laca strain) individually in each cage for 3 weeks and various drug treatments were given for a period of 5 days before the start of the experiments. The various behavioural parameters examined included pentobarbitone-induced sleep (sleep latency and duration), analgesia (tail-ssick test) and locomotor activity, respectively. BR-16A (100 mg/kg and 200 mg/kg) treatment for 5 days significantly reversed the social isolation stress-induced prolongation of onset and decrease in pentobarbitone-induced sleep, increased total motor activity and stress-induced antinociception. When diazepam (0.5 mg/kg), a benzodiazepine agonist, was co-administered with BR-16A (100 mg/kg), it significantly potentiated the reversal of pentobarbitone-induced shortening of sleep time effects; increased locomotor activity and stress induced antinociceptive effects. However, the sleep latency was not decreased significantly. Further, ssumazenil (2 mg/kg), a benzodiazepine receptor antagonist and FG 7142 (10 mg/kg), an inverse agonist, when co-administered with BR-16A (100 mg/kg), showed no significant reversal on pentobarbitone-induced hypnosis, locomotor activity and social isolation-induced antinociception compared with their effects per se. The present study demonstrated the antistress effects of BR-16A preparation against social isolation-induced stress. The present study also suggests that the GABAergic system may be involved in its antistress effect.

Animals↗

Involvement of peripheral prostaglandins in formalin-induced nociceptive behaviours in the orofacial area of rats.

Prostaglandins (PGs) are known to be involved in the pathogenesis of inflammation and pain. However, their role in orofacial pain is not clearly understood. The present study was undertaken to determine the effect of systemic and locally administered nonsteroidal anti-inflammatory drugs (NSAIDs) on the role of PGs in orofacial pain induced by formalin in rats. The subcutaneous injection of formalin into the rat upper lip generated behavioural responses that lasted for several minutes. The orofacial responses due to formalin were seen in two distinct phases, the early response (0-3 min) and the continuous prolonged response (9-45 min). Systemic administration of ketorolac or diclofenac (10 and 30 mg/kg, i.p.) significantly attenuated formalin-induced nociceptive behaviour in the phase-2, but not in the phase-1 of the formalin test. Similarly, subcutaneous (local) administration of ketorolac or diclofenac in the orofacial area (100 and 300 microg/lip) markedly decreased the phase-2 nociceptive response due to formalin. However, both the drugs had no effect on the phase-1 response of the formalin test. These results suggest that PGs, particularly peripheral PGs are involved in nociceptive behaviour following formalin injection in the orofacial area.

Animals↗

Sildenafil induces hyperalgesia via activation of the NO-cGMP pathway in the rat neuropathic pain model.

Persistent stimulation of nociceptors and C-fibers by tissue injury causes hyperalgesia and allodynia by sensitization of nociceptors and facilitation of synaptic transmission in the spinal cord. The important participant in the inflammatory response of injured peripheral nerve may be nitric oxide (NO). The aim of the present study was to test the sensitivity of PDE5 inhibitor sildenafil in chronic constriction injury (CCI) model a rat model of neuropathic pain. Sciatic nerve injury is associated with development of hyperalgesia 14 days after the nerve ligation. Sildenafil (100 and 200 microg/rat, i.t.) produced a significant decrease in pain threshold, which in lower dose did not alter the nociceptive threshold. The hyperalgesic effect of sildenafil was blocked by L-NAME and methylene blue (MB), which on per se treatment showed antinociceptive effect in nerve ligated rats. The results from the present study indicated that the major activation of NO-cGMP pathway in the chronic constriction injury model of neuropathic pain. The aggravation of hyperalgesic response might be due to the increased cGMP levels resulting in PKG-I activation and its upregulation.

3',5'-Cyclic-GMP Phosphodiesterases↗

Rofecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor potentiates the anticonvulsant activity of tiagabine against pentylenetetrazol-induced convulsions in mice.

Numerous studies have implicated prostaglandins as potential modulators in seizure activity. The objective of the present study was to elucidate the effect of rofecoxib (selective COX-2 inhibitor) alone or in combination with newer antiepileptic drug tiagabine (gamma-amino acid reuptake inhibitor) against pentylenetetrazol (PTZ) (80 mg/kg, i.p.)-induced chemoconvulsions in mice. Rofecoxib or tiagabine was administered 45 min prior to the PTZ challenge. In combination study, rofecoxib was administered 10 min before tiagabine and after 35 min the animals were challenged with convulsive dose of PTZ. Mean onset time of jerks, clonus and extensor phases following PTZ challenge was noted. Pretreatment with rofecoxib (1-5.0 mg/kg, i.p.) or tiagabine (1-10 mg/kg, i.p.) dose dependently protected the animals against PTZ-induced convulsions. The mean onset time of jerks, clonus and extensor phase were increased. A subeffective dose of rofecoxib (0.5 mg/kg, i.p.) potentiated the effect of subprotective dose of tiagabine (0.5 mg/kg, i.p.). The results of the present study suggested that the protective effect of rofecoxib, a COX-2 inhibitor against PTZ-induced convulsions may be possibly through the GABAergic modulation. Rofecoxib may have a place as adjuvant therapy with standard antiepileptic drugs such as tiagabine in the treatment of epilepsy.

Animals↗

Comparative brain cholinesterase-inhibiting activity of Glycyrrhiza glabra, Myristica fragrans, ascorbic acid, and metrifonate in mice.

The central cholinergic pathways play a prominent role in the learning and memory processes. Acetylcholinesterase is an enzyme that inactivates acetylcholine. The present study was undertaken to estimate the acetylcholinesterase- inhibiting activity of extracts of Glycyrrhiza glabra, Myristica fragrans seeds, and ascorbic acid and compare these values with a standard acetylcholinesterase-inhibiting drug, metrifonate. Aqueous extract of G. glabra (150 mg/kg p.o. for 7 successive days), n-hexane extract of M. fragrans seeds (5 mg/kg p.o. for 3 successive days), ascorbic acid (60 mg/kg i.p. for 3 successive days), and metrifonate (50 mg/kg i.p.) were administered to young male Swiss albino mice. Acetylcholinesterase enzyme was estimated in brains of mice. G. glabra, M. fragrans, ascorbic acid, and metrifonate significantly decreased acetylcholinesterase activity as compared with their respective vehicle-treated control groups.

Acetylcholinesterase↗

Effect of BR-16A (Mentat), a polyherbal formulation on drug-induced catalepsy in mice.

Parkinson's disease (PD) is a neurodegenerative disease characterized by the selective loss of dopamine (DA) neurons of the substantia nigra pars compacta (SNc). The events, which trigger and/or mediate the loss of nigral DA neurons, however, remain unclear. Neuroleptic-induced catalepsy has long been used as an animal model for screening drugs for Parkinsonism. Administration of haloperidol (1 mg/kg, ip) or reserpine (2 mg/kg, ip) significantly induced catalepsy in mice. BR-16A (50 and 100 mg/kg, po), a polyherbal formulation or ashwagandha (50 and 100 mg/kg, po), significantly reversed the haloperidol or reserpine-induced catalepsy. The results indicate that BR-16A or ashwagandha has protective effect against haloperidol or reserpine-induced catalepsy and provide hope that BR-16A could be used in preventing the drug-induced extrapyramidal side effects and may offer a new therapeutic approach to the treatment of Parkinson's disease.

Animals↗

Resveratrol, a polyphenolic phytoalexin attenuates thermal hyperalgesia and cold allodynia in STZ-induced diabetic rats.

The effects of resveratrol, a polyphenolic phytoalexin present in red wine have been investigated on hyperalgesia and cold allodynia in streptozotocin (STZ) induced diabetic rats. Diabetes was induced by a single intraperitoneal injection of streptozotocin (65mg/kg). After 4-weeks of STZ injection, diabetic rats exhibited a significant thermal hyperalgesia and cold allodynia along with increased plasma glucose and decreased body weights as compared with controls rats. Chronic treatment with resveratrol (10mg/kg orally) from week 4 to week 6 significantly attenuated the cold allodynia and thermal hyperalgesia. The results emphasize the role of oxidative stress in development of hyperalgesia and cold allodynia in diabetic animals and point towards the potential of resveratrol as an adjuvant therapy for the prevention and treatment of diabetic neuropathy.

Animals↗

Structure determination of CdS and ZnS nanoparticles: direct modeling of synchrotron-radiation diffraction data.

We introduce a modified method of powder-diffraction data analysis to obtain precise structural information on freestanding ZnS and CdS nanoparticles with diameters well below 5 nm, i.e., in a range where common bulk-derived approaches fail. The method is based on the Debye equation and allows us to access the crystal structure and the size of the particles with high precision. Detailed information on strain, relaxation effects, stacking faults, and the shape of the particles becomes available. We find significant size differences between our new results and those obtained by established methods, and conclude that a mixed zinc-blende/wurtzite stacking and significant lattice distortions occur in our CdS nanoparticles. Our approach should have direct impact on the understanding and modeling of quantum size effects in nanoparticles.

Journal Article↗

Resveratrol, a polyphenolic phytoalexin, attenuates diabetic nephropathy in rats.

Diabetic nephropathy is a serious microvascular complication and one of the main causes of end-stage renal disease. Various studies have revealed that increased oxidative stress is a major pathophysiological mechanism which is involved in the etiology of diabetic nephropathy. Resveratrol, a polyphenolic phytoalexin present in red wine, is known to possess potent antioxidant properties and thus we aimed to examine its effect on renal function and oxidative stress in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by a single intraperitoneal injection of STZ (65 mg/kg) in rats. After 4 weeks of STZ injection, rats were divided into four groups: the control rats, diabetic rats and diabetic rats treated with resveratrol (5 and 10 mg/kg, orally) respectively from week 4 up till week 6. At the termination of the experiments, urine albumin excretion, urine output, serum creatinine, blood urea nitrogen, creatinine and urea clearance were measured. The levels of the renal oxidative stress markers malonaldehyde and glutathione and the antioxidant enzymes superoxide dismutase and catalase were measured in kidney homogenate. STZ-injected rats showed significant increases in blood glucose, polyuria, proteinuria and a decrease in body weight compared with age-matched control rats. After 6 weeks, diabetic rats exhibited renal dysfunction, as evidenced by reduced creatinine and urea clearance, and proteinuria along with a marked increase in oxidative stress, as determined by lipid peroxidation and activities of key antioxidant enzymes. Treatment with resveratrol significantly attenuated renal dysfunction and oxidative stress in diabetic rats. The present study reinforces the important role of oxidative stress in diabetic kidney and points towards the possible antioxidative mechanism being responsible for the renoprotective action of resveratrol.

Animals↗

Effect of pH on photoluminescence enhancement in Pb-doped ZnS nanoparticles.

Narrowly dispersed Pb-doped zinc sulfide nanoparticles were synthesized at room temperature using a chemical method in which the nanoparticle surfaces were passivated using mercaptoethanol. The maximum intensity of the broad green luminescence (approximately 530 nm) from these nanoparticles was observed at an optimum dopant concentration of 0.104 Pb wt%. The emission intensity was found to depend on the synthesis pH conditions, thus yielding maximum intensity at 5.0 pH. Comparatively lower emission intensities were observed for the other pH values (2.5-9.0 pH range). This may be due to the pH-dependent Cl- (as well as Na+) incorporation into the ZnS matrix, which possibly helps in inducing required density of impurity (donor/co-activator) states in the energy gap of ZnS nanoparticles. X-ray diffraction analysis using Debye functional analysis showed that the particle size is 2.8+/-0.3 nm.

Journal Article↗

Synthesis and spectral properties of DNA capped CdS nanoparticles in aqueous and non-aqueous media.

Synthesis of novel cadmium sulphide nanoparticles has been carried out in aqueous and non-aqueous media. DNA has been added during the synthesis of the nanoparticles, which results into cadmium-rich nanoparticles forming a stable complex with DNA. These particles exhibit strong fluorescence, spectral nature of which depends upon the medium in which the particles are synthesized. When interacted with proteins, fluorescence peak intensity of CdS nanoparticles increases considerably. It is possible that such CdS nanoparticles would be useful as a protein sensor.

Biosensing Techniques↗

Protective effect of quercetin on alcohol abstinence-induced anxiety and convulsions.

Chronic administration of ethanol (2 g/kg, p.o.) on days 1-6 and its withdrawal produced an anxiogenic reaction in mice as assessed in the mirrored-chamber test. Daily administration of quercetin (25 or 50 mg/kg, p.o.) prior to ethanol for 6 days prevented withdrawal-induced anxiety in mice. However, acute administration of a single dose of quercetin (50 mg/kg) to animals withdrawn from ethanol, i.e., on day 7, did not prevent withdrawal-induced anxiety. Ethanol withdrawal also induced a significant increase in the locomotor activity of mice indicating an anxiogenic response. Daily administration of quercetin (25 or 50 mg/kg, p.o.) prior to ethanol for 6 days prevented withdrawal-induced increased locomotor activity. Ethanol withdrawal also sensitized the convulsogenic reaction to pentylenetetrazole (PTZ). A non-convulsive dose (40-60 mg/kg) of PTZ produced full-blown convulsions and increased mortality in ethanol-withdrawn mice. Both acute and chronic administration of quercetin (25 or 50 mg/kg, p.o.) produced a significant protection against ethanol withdrawal-induced reduction in PTZ threshold in mice. The result suggests the protective effect of this safe drug, quercetin, in the management of ethanol withdrawal reactions.

Alcohol Withdrawal Seizures↗

Protective effects of nimesulide (COX Inhibitor), AKBA (5-LOX Inhibitor), and their combination in aging-associated abnormalities in mice.

Several inflammatory processes play a critical role in brain aging and are associated with increased vulnerability to neurodegeneration. Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX), two enzymes involved in the oxygenation of the arachidonic acid, are upregulated in the central nervous system during aging and are associated with different aging-related brain pathologies. The present experiment was performed to study the effects of 5-LOX inhibitor, acetyl-11-keto-beta-boswellic acid (AKBA), nimesulide (preferential COX-2 inhibitor), and their combination on cognitive performance of young and aged mice, using elevated plus maze test. Chronic administration of AKBA (100 mg/kg, p.o.) and nimesulide (2.42 mg/kg, p.o.) for 15 days significantly reversed the aging-induced retention deficit in mice. Coadministration of AKBA and nimesulide enhanced the cognitive performance in aged mice when compared with that in per se treatment. The aging-related increase in oxidative damage (increased LPO and decreased GSH) was reversed by AKBA, nimesulide, and their combination. Further, per se COX and LOX inhibitors and their combination did not produce any alteration in gastrointestinal parameters; they also reversed the aging-induced motor dysfunction in the aged animals. On the basis of these observations, present findings indicated that the combination of COX and LOX inhibitors (dual inhibitors) may provide a new therapeutic innovation for the treatment of aging-related brain disorders such as Alzheimer's disease and different motor dysfunctions with adequate gastrointestinal tolerability.

Aging↗

Hypocholesterolemic activity of some novel azetidin-2-ones in diet and diabetes induced hypercholesterolemia in rats.

Some novel substituted azetidin-2-ones (5-8) were synthesized via [2 + 2] cycloaddition reactions of imines and ketenes and evaluated for their ability to prevent diet and diabetes induced hypercholesterolemia. The test compounds 5a and 7a significantly (p < 0.01) inhibited the rise in serum total cholesterol induced by peanut oil (5.5%), cholesterol (1.5%) and cholic acid (0.5%) diet in both acute and chronic models in a dose dependent manner. Compound 5a also raised the high density lipoprotein-cholesterol levels in chronic diet models by peanut oil (5.5%), cholesterol (1.5%) and cholic acid (0.5%). In a diabetes induced model of hypercholesterolemia, the test compounds were evaluated for preventing diabetes-induced hypercholesterolemia (protocol 1) as well as for lowering post diabetic hypercholesterolemia (protocol 2). Test compounds 5a-g and 7a-d significantly (p < 0.05) reduced serum total cholesterol with a greater reduction in protocol 1 as compared with protocol 2. Based on SAR studies, the substituents that favor hypocholesterolemic activity around the azetidin-2-one nucleus are discussed and a possible mechanism of action is proposed on the basis of their differential effects in two protocols of diabetes-induced hypercholesterolemia.

Animals↗

Possible analgesic and anti-inflammatory interactions of aspartame with opioids and NSAIDs.

The purpose of the present study was to investigate analgesic and anti-inflammatory properties of aspartame, an artificial sweetner and its combination with various opioids and NSAIDs for a possible synergistic response. The oral administration of aspartame (2-16mg/kg, po) significantly increased the pain threshold against acetic acid-induced writhes in mice. Co-administration of aspartame (2mg/kg, po) with nimesulide (2 mg/kg, po) and naproxen (5 mg/kg, po) significantly reduced acetic acid-induced writhes as compared to effects per se of individual drugs. Similarly when morphine (1 mg/kg, po) or pentazocine (1 mg/kg, po) was co-administered with aspartame it reduced the number of writhes as compared to their effects per se. Aspartame (4,8,16 mg/kg, po) significantly decreased carrageenan-induced increase in paw volume and also reversed the hyperalgesic effects in rats in combination with nimesulide (2 mg/kg, po). The study indicated that aspartame exerted analgesic and anti-inflammatory effects on its own and have a synergistic analgesic response with conventional analgesics of opioid and non-opioid type, respectively.

Acetic Acid↗