Biomedical subjects

Y K Gupta

Publications and source records attributed to Y K Gupta.

At least 55 records · Page 3Linked to original sources

PubMed2001

Abuse liability of diazepam through different routes.

Abuse liability of diazepam was examined among experienced drug users. The subjects, randomly divided into two groups, each having eight subjects, received diazepam, 15 mg intravenously (gr. 1) and 30 mg orally (gr. 2). Subjective states, drug liking, sedation and euphoria were assessed at pre-drug, 15 min, 120 min and 240 min post-drug administration. In addition, brief assessment to evaluate euphoria and sedation was carried out at 5 min and 45 min for subjects in gr. 1, and at 45 min and 150 min for those in gr. 2. Plasma diazepam level was also estimated. Results indicate those subjects in gr. 1 reported quicker and higher euphoria, drug liking, subjective effects and higher plasma level. The study suggests that route of administration of a compound which has faster onset of action is associated with more liability of abuse.

Adult↗

PubMed2001

Reversal of paclitaxel induced neutropenia by Withania somnifera in mice.

The effect of aqueous extract of Withania somnifera (L. Solanaceae) was studied against paclitaxel induced neutropenia in mice. After paclitaxel 1 mg/kg, i.v. administration significant fall in total WBC and absolute neutrophil count was observed on day 3 and day 5. W. Somnifera (200 mg/kg, p.o.) per se produced significant increase in neutrophil counts. W. somnifera (200 mg/kg, p.o.) when administered for 4 days before paclitaxel treatment and continued for 12 days caused significant reversal of neutropenia of paclitaxel. The findings of the study suggest the potential of W. somnifera as an adjuvant during cancer chemotherapy for the prevention of bone marrow depression associated with anticancer drugs.

Animals↗

PubMed2001

Aspirin modulates the anticonvulsant effect of diazepam and sodium valproate in pentylenetetrazole and maximal electroshock induced seizures in mice.

Release of prostaglandins in brain after spontaneous and experimentally induced seizures, has been demonstrated. The possible role of prostaglandins in modulation of seizure activity is still inconclusive. In the present study, the effects of aspirin and its interaction with the anticonvulsants (diazepam and sodium valproate) were studied in pentylenetetrazole (PTZ) and maximal electroshock (MES) induced seizures in mice. Aspirin 50, 100, and 500 mg/kg, i.p. was administered 45 min before the pentylenetetrazole (60 mg/kg, i.p.) and MES (60 mA, 0.2 s duration via car clip electrodes) challenge. In MES seizures significant protection was seen with aspirin 100 mg/kg where as higher dose of aspirin 500 mg/kg was required to elicit maximum protection against PTZ seizures. Sub anticonvulsant dose of sodium valproate 150 mg/kg, i.p. and aspirin 50 mg/kg i.p. showed complete protection in MES seizures and the same dose of sodium valproate offered superior protection in PTZ seizures than either drug used alone. When mice were pretreated with combination of diazepam 0.5 mg/kg and aspirin 50 mg/kg protection was significantly enhanced in PTZ seizures. However, aspirin did not show any significant protection with subanticonvulsant dose of diazepam against MES seizures. The present study suggests that prostaglandins may have anticonvulsant potential and also may have modulatory effect on anticonvulsant effect of conventional antiepileptic drugs.

Animals↗

PubMed2001

Antiepileptic activity of Panax ginseng against pentylenetetrazole induced kindling in rats.

In the present study, Panax ginseng was evaluated for its antiepileptic activity against pentylenetetrazole (PTZ) induced chemical kindling in rats. PTZ was injected at the dose of 30 mg/kg, i.p. on alternate days and the occurrence of generalized tonic clonic convulsions were considered as the end point. One group received Panax ginseng every day, at a dose of 100 mg/kg, 30 min prior to PTZ injection whereas the other group received an equal volume of distilled water to serve as control. In a separate group the rats were evaluated for motor performance tests after Panax ginseng. The rats treated with Panax ginseng showed significant protection as compared to vehicle treated PTZ injected rats. The study suggests to potential of Panax ginseng against seizures.

Animals↗

PubMed2000

Etoposide encapsulated in positively charged liposomes: pharmacokinetic studies in mice and formulation stability studies.

Etoposide is an antineoplastic agent which acts by forming a ternary complex with topoisomerase II and DNA, causing DNA breaks and cell death. In recent studies we have demonstrated that encapsulation in liposomes increases the antitumour efficacy and reduces the adverse effects associated with etoposide. The present study was thus conducted to evaluate whether encapsulation in cationic liposomes altered the pharmacokinetics of etoposide and to study the effect of cholesterol incorporation on the stability of the liposomes. Etoposide-encapsulated unilammellar liposomes were synthesized by thin film hydration followed by extrusion. The drug was administered to Swiss albino mice at a dose of 10 mg kg(-1). The concentration of the drug in plasma was analysed at different time points till 360 min after injection, using a h.p.l.c. method. The terbium chloride-dipicolinic acid interaction method was applied to study the stability of the formulation in mouse serum and also following storage at 0( composite function)C over a period of time. The effect of the free and liposomal drug on myelosuppression was evaluated at 10 mg m(-2)and 40 mg m(-2)dose levels by quantifying blood cell counts on day 15 and day 21 following a 5 day course of therapy. Encapsulation in cationic liposomes increased the area under the concentration vs time curve to 42.98 microghml(-1)from 24.18 microghml(-1)in the case of the free drug. Half-life (beta) was 58. 62 and 186 min in the case of free and liposomal etoposide, respectively. In the stability studies, incorporation of cholesterol progressively stabilized the formulation in serum. The use of sucrose at increasing concentrations as a cryoprotectant also increased the shelf stability of the formulation at 0( composite function)C. Toxicity studies using a dose of pure drug revealed that though myelosuppression was evident in both liposomal- and free drug-treated groups on day 15 it was reversed by day 21 following initiation of therapy. The present findings suggest that liposomes could serve as an alternative mode of delivery for etoposide.

Analysis of Variance↗

PubMed2000

Galanin knockout mice reveal nociceptive deficits following peripheral nerve injury.

The neuropeptide galanin has been identified as a potential neurotransmitter/neuromodulator within the central nervous system. In the present study, the role of endogenous galanin in nociceptive processing in the nervous system has been analysed by using mice carrying a targeted mutation in the galanin gene. Supporting this, the effect of chronic administration of exogenous galanin on nociceptive sensory inputs has been assayed in adult rats. In the absence of peripheral nerve injury, the sensitivity to threshold noxious stimuli is significantly higher in galanin mutant mice than wild-type controls. Following peripheral nerve injury, in conditions under which endogenous galanin levels are elevated, spontaneous and evoked neuropathic pain behaviours are compromised in mutant mice. Conversely, chronic intrathecal delivery of exogenous galanin to nerve-intact adult rats is associated with persistent behavioural hypersensitivity, a significant increase in c-fos expression and an increase in PKCgamma immunoreactivity within the spinal cord dorsal horn. The present results demonstrate that a relationship exists between the degree of nerve injury-induced galanin expression and the degree of behavioural hypersensitivity, and show that galanin may play a role in nociceptive processing in the spinal cord, with interrelated inhibitory and excitatory effects.

Animals↗

PubMed2000

Comparison of various calpain inhibitors in reduction of light scattering, protein precipitation and nuclear cataract in vitro.

PURPOSE: To compare effects of calpain inhibitors on in vitro light-scattering in rat lens soluble protein and calcium-ionophore (A23187)-induced cataract formation in cultured rat lenses. METHODS: Rat lens soluble protein was hydrolyzed for 24 hours by activation of endogenous lens calpain. Ten calpain inhibitors were tested in this model at 10 and 25 microM concentration. As an index of protein precipitation, light scattering was measured daily at 405 nm for 8 days. Lens proteins were analyzed by isoelectric-focussing. Subsequently, rat lenses were cultured for 5 days with 10 microM A23187. Calpain inhibitors (SJA6017, MDL28170, AK295 and PD150606), which inhibited light-scattering were tested at 100 microM concentration in this model. Cataract evaluation, isoelectric-focussing and calcium determinations were performed. RESULTS: At 25 microM concentration AK295, SJA6017, E-64, PD-150606 and MDL28170 produced greater than 25% inhibition of light-scattering. Isoelectric-focussing revealed that addition of Ca(2+) produced characteristic crystallin proteolysis and aggregation patterns. AK295, SJA6017, MDL28170 and E64c prevented these changes. Lenses cultured in A23187 exhibited nuclear cataract, elevated calcium and proteolysis and aggregation of crystallins. Co-culture with SJA6017, MDL28170 and E64c reduced A23187-induced nuclear opacities, proteolysis and aggregation of crystallins without affecting increased total calcium. CONCLUSIONS: Endogenous calpain-activation model and A23187-induced cataract model can be used sequentially to screen calpain inhibitors for potential anti-cataract activity. Proteolytic changes in lens cortex after exposure to A23187 are also due to calpain activation. AK295, SJA6017 and MDL28170 possess efficacy against calcium-induced models of rodent cataracts. Use of calpain inhibitors represents a promising approach to cataract therapy.

Animals↗

PubMed2000

Effect of antioxidants on pyrogallol-induced delay in gastric emptying in rats.

The effect of a free radical generator pyrogallol on gastric emptying was studied in rats. Pyrogallol at doses of 25, 50, 100 and 150 mg/kg (i.p.) produced dose-dependent inhibition of gastric emptying. Pretreatment with vitamin C (100 and 500 mg/kg, p.o.), and vitamin E (100 and 500 mg/kg, p.o.) significantly reversed the inhibition in gastric emptying caused by pyrogallol 100 mg/kg. However, the combination of vitamin C and vitamin E (100 mg/kg) produced synergistic effect. Glutathione (100 mg/kg i.v.) 5-min pretreatment also reversed the inhibition of gastric emptying caused by pyrogallol 100 mg/kg. Ondansetron (3 mg/kg, p.o.) significantly reversed the pyrogallol effect. The effect of pyrogallol on malondialdehyde (MDA) levels and 5-HT levels in the stomach tissue was also studied. Pyrogallol at a dose of 100 mg/kg, i.p., significantly increased MDA levels and 5-HT levels in the stomach. Pretreatment with a combination of vitamin C and vitamin E (100 mg/kg, p.o.) and glutathione (100 mg/kg, i.v.) significantly ameliorated the rise in stomach tissue MDA caused by pyrogallol but had no significant effect on the rise in 5-HT levels caused by pyrogallol. The effect of different doses of 5-HT on gastric emptying was also studied. 5-HT had a differential effect on gastric emptying. The low and high doses (0.1, 0.3 and 30 mg/kg, i.p.) significantly inhibited the gastric emptying while doses ranging from 1 to 10 mg/kg, i.p., had no significant effect on the gastric emptying. The pretreatment with antioxidants, combination of vitamin C and vitamin E (100 mg/kg each, p.o.) and glutathione (100 mg/kg, i. v.) had no effect on the 5-HT (0.3 mg/kg, i.p.)-induced delay in gastric emptying. The result indicate the role of free radicals gastric emptying, and antioxidants may be of potential therapeutic value in disease conditions where free radicals are known to be released and the gastrointestinal effects are observed as symptoms or side effects of drug therapy.

Animals↗

PubMed2000

Antiepileptic drug therapy in the twenty first century.

In the last 25 years, particularly the last decade, there have been many advances relating to all aspects of epilepsy i.e. pathophysiology, diagnosis, pharmacotherapy and surgical interventions. Noteworthy has been the progress in terms of understanding of the established antiepileptic drugs (AEDs) and introduction of several newer agents developed rationally, on the basis of now available information on the biochemical changes in the epileptic brain. Data is accumulating regarding the use of newer agents but they still need to stand the test of time. Many of the newer AEDs may offer a better tolerability because of favorable pharmacokinetic characteristics and minimal drug interactions. However, serious adverse events have been associated with felbamate and lamotrigine already and for other newer agents reliable and accurate data needs to be generated.

Animals↗

PubMed2000

Anti-inflammatory activity of sodium pyruvate--a physiological antioxidant.

The anti-inflammatory activity of sodium pyruvate was evaluated in acute and chronic models of inflammation in rats. Oral administration of sodium pyruvate at three different dose levels of 125, 250 and 500 mg/kg body weight significantly inhibited the carrageenan induced acute paw edema in a dose dependent manner. The effect of 500 mg/kg sodium pyruvate was comparable to that of 12.5 mg/kg of standard diclofence. In Freund's adjuvant arthritis model, oral administration of sodium pyruvate at the submaximal dose of 250 mg/kg once daily upto one week before Freund's adjuvant injection and immediately by the same route on the 7th day of adjuvant injection significantly reduced the edema at 18 hours after the challenge. The treatment was continued for 14 days thereafter in two divided doses of 125 mg/kg in the morning and 125 mg/kg in the evening. Sodium pyruvate showed significant anti-inflammatory activity at the 14th day (chronic phase) also. To conclude, sodium pyruvate exhibited significant anti-inflammatory activity in both the models of inflammation which could be attributed to its antioxidant properties.

Animals↗

PubMed1999

Acute intracranial hypertension-induced inhibition of gastric emptying: evaluation in conscious rats.

To study the effect of raised intracranial pressure (ICP)-induced alterations in gastric emptying, and their modulation by pharmacological interventions, an experimental model was standardized in rats. A test meal of methylcellulose and phenol red was administered intragastrically. ICP was raised to 40, 60 and 80 mmHg by connecting a buffered saline pressure head to an intracerebroventricular (i.c.v.) cannula. Gastric emptying was estimated after killing the animals, from the residual stomach phenol red content. Inhibition of gastric emptying was observed when ICP was raised, the maximum being at 80 mmHg ICP (percent gastric emptying 26.5%+/-2.8 vs. 83.4+/-4.7 in sham-ICP). Pretreatment with clonidine, prazosin or ondansetron did not modify the raised ICP-induced inhibition of gastric emptying. Cisapride was ineffective at 1 mg/kg but caused a partial reversal at the 5- and 10-mg/kg doses (46.9+/-3.1% and 42.6+/-4.0%, respectively). Carbachol at a lower dose of 0.1 mg/kg i.p., produced a greater reversal (78.3+/-6.0%) than did the high dose (52.8+/-4.1). Bretylium partially reversed the inhibition of gastric emptying (45.7+/-4.3%). The protective effect of carbachol and cisapride suggests that suppression of vagal activity due to increased ICP may play an important role in the inhibition of gastric emptying due to intracranial hyper-tension.

Acute Disease↗

PubMed1999

Chimeric peptide of Met-enkephalin and FMRFa induces antinociception and attenuates development of tolerance to morphine antinociception.

A synthetic chimeric peptide of Met-enkephalin and FMRFamide (YGGFMKKKFMRFa), based on MERF was synthesized. This peptide was tested for possible antinociceptive effects using the tail flick test in mice. The effect of the chimeric peptide on morphine antinociception and development of tolerance to the antinociceptive action of morphine was also investigated. The chimeric peptide produced significant, dose-dependent antinociception (40, 60 and 90 mg/kg) in the tail flick test. Pretreatment with naloxone (5 mg/kg, IP) significantly attenuated the antinociceptive effect induced by the chimeric peptide (90 mg/kg, IP), indicating involvement of an opioidergic mechanism. In combination experiments with morphine, the antinociceptive dose of the chimeric peptide (60 mg/kg, IP) potentiated morphine (7 mg/kg, IP) antinociception. A low dose of the chimeric peptide (10 mg/kg, IP), that did not produce significant antinociception on its own, also potentiated morphine antinociception. In the tolerance studies, male albino mice received twice daily injections of morphine (20 mg/kg, IP) followed by either saline (0.1 ml) or chimeric peptide (80 mg/kg, IP) for a period of 4 days. A control group received twice daily injections of saline (0.1 ml) for the same period. When tested on Day 5, tolerance to antinociceptive action of morphine (15 mg/kg, IP) was evidenced by decreased response in chronic morphine plus saline treated mice compared to control group. Concurrent administration of chimeric peptide (80 mg/kg, IP) with morphine significantly attenuated the development of tolerance to the antinociceptive action of morphine. The preliminary results of this study demonstrate that peripherally administered chimeric peptide can produce dose dependent, naloxone reversible, antinociception; potentiate morphine antinociception and attenuate morphine tolerance, indicating a possible role of these type of amphiactive sequences in antinociception and its modulation. These chimeric peptides may also prove to be useful tools for further ascertaining the role of FMRFa family of peptides in mechanisms leading to opiate tolerance and dependence.

Analgesics↗

PubMed1999

Comparative studies on topical lomefloxacin and ciprofloxacin on ocular kinetic and experimental corneal ulcer.

Fluoroquinolones are antimicrobial agents that have a broad spectrum of activity and that are widely used against many of the ocular pathogens responsible for conjunctivitis, blepharitis, corneal ulcers, etc. The aim of our study was to compare the ocular pharmacokinetics of ciprofloxacin (0.3% w/v) and lomefloxacin (0.3% w/v) by HPLC after a single application of 50 microl topically. The study was also extended to compare their efficacy in experimentally-induced corneal ulcers. In ocular kinetic studies, lomefloxacin showed nearly 10 times more ocular bioavailability in aqueous humor as compared to ciprofloxacin. Lomefloxacin showed a Cmax of 1.62 microg/ml at the Tmax of 1 hr whereas ciprofloxacin showed a Cmax of 102.8 ngs/ml at the Tmax of 1 hr. Lomefloxacin was found to have significant efficacy in the healing of Staphylococcus aureus-induced corneal ulcers and associated lesions. Moreover, aqueous formulation oflomefloxacin showed a good compatibility at neutral pH. The results of our study indicate that a suitable treatment regimen with lomefloxacin (0.3%) therapy could be an excellent therapeutic alternative over ciprofloxacin in bacterial keratitis.

Administration, Topical↗

PubMed1999

Effect of adenosinergic modulation on the anticonvulsant effect of phenobarbitone and carbamazepine.

Adenosine has been demonstrated to have an anticonvulsant action which is mediated predominantly by the adenosine A1 receptor subtype. The present study was conducted to determine if the adenosinergic system and adenosine A1 receptors are involved in the anticonvulsant action of the antiepileptic drugs phenobarbitone and carbamazepine, in pentylenetetrazole (PTZ)-induced seizures in rats. The specific adenosine A1 receptor antagonist, DPCPX (1 mg/kg i.p.), had no effect on the anticonvulsant action of the two antiepileptic drugs. However, the nonspecific adenosine receptor antagonist, theophylline (50 and 100 mg/kg i.p.), reversed the anticonvulsant action of carbamazepine completely and that of phenobarbitone partially. This suggests that adenosine A1 receptors do not mediate the anticonvulsant effects of these agents. When phenobarbitone/carbamazepine were coadministered with adenosine/N6-cyclopentyladenosine (CPA), a specific adenosine A1 receptor agonist, an enhancement in protection against PTZ-induced seizures was observed. The diversity of anticonvulsant mechanism of carbamazepine/phenobarbitone and that of adenosinergic agents could be responsible for this effect.

Adenosine↗

PubMed1998

Reversal of cisplatin-induced delay in gastric emptying in rats by ginger (Zingiber officinale).

Cisplatin causes nausea, vomiting and inhibition of gastric emptying. We have demonstrated the antiemetic effect of the acetone and ethanolic extract of ginger (Zingiber officinale, Roscoe, Zingiberacae) against cisplatin-induced emesis in dogs. In the present study, the acetone and 50% ethanolic extract of ginger in the doses of 100, 200 and 500 mg/kg (p.o.) and ginger juice, in the doses of 2 and 4 ml/kg, were investigated against cisplatin effect on gastric emptying in rats. All three ginger preparations significantly reversed cisplatin-induced delay in gastric emptying. The ginger juice and acetone extract were more effective than the 50% ethanolic extract. The reversal produced by the ginger acetone extract was similar to that caused by the 5-HT3 receptor antagonist ondansetron; however, ginger juice produced better reversal than ondansetron. Therefore, ginger, an antiemetic for cancer chemotherapy, may also be useful in improving the gastrointestinal side effects of cancer chemotherapy.

Animals↗

PubMed1998

Delayed manifestation of ultra violet radiation induced erythema in guinea pigs by sodium pyruvate--a free radical scavenger.

Sodium pyruvate, a free radical scavenger was evaluated for anti-inflammatory activity using UV radiation induced dermal erythema on guinea pig and compared with that of standard naproxen. Oral as well as topical pyruvate exhibited significant activity against UV induced dermal erythema model and the activity was comparable to that of naproxen. In the other pharmacodynamic studies, such as the studies on rat blood pressure, isolated guinea pig ileum and rat uterus, it showed no effect on any of these. In conclusion, sodium pyruvate showed a significant protection in the UV induced dermal erythema in guinea pigs. It also showed good absorption in UV-B range and this property can be utilised to develop the sodium pyruvate as a sunscreening agent.

Animals↗

PubMed1998

Influence of adenosine agonists and antiepileptic drugs on theophylline-induced seizures in rats.

Seizures is a major toxicity of theophylline. The mechanism of theophylline-induced seizures is not known, but antagonism at adenosine receptors may be a possibility. The effect of pretreatment with different doses of adenosine (100, 500 and 1000 mg/kg, i.p.), and the adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA), 1, 5 and 10 mg/kg, i.p., was studied against seizures induced by theophylline in rats. Both these drugs, at all dose levels tested, failed to protect theophylline seizures. Thus adenosinergic system is unlikely to be involved in mediating the convulsant action of theophylline. On the other hand, the conventional antiepileptic drugs, i.e. diazepam (4 mg/kg), sodium valproate (300 mg/kg) and phenobarbitone (50 mg/kg), but not carbamazepine, afforded some protection. The modification of course of seizures, by the antiepileptic drugs suggests the involvement of some other alternate mechanism in theophylline-induced seizures.

Adenosine↗

PubMed1998

Generalized odontodysplasia--a case report.

Odontodysplasia is a relatively uncommon condition that can affect both primary and permanent dentition. It is characterized by defective formation of both enamel and dentin, with enlarged pulp chambers and root canals with open apices. It is usually a localised condition where one or few teeth may be involved. Sometimes, an entire quadrant or more than one quadrant may be involved but generalized involvement is extremely rare. An interesting case of a generalized odontodysplasia affecting both primary and permanent dentition in an eight year old girl is presented here.

Child↗