Biomedical subjects

Y K Gupta

Publications and source records attributed to Y K Gupta.

At least 19 recordsLinked to original sources

PubMed2006

Effect of Ocimum sanctum Linn. on cardiac changes in rats subjected to chronic restraint stress.

Male Wistar rats were subjected to chronic restraint stress (CRS; 6 h/day for 21 days) alone or along with either hydroalcoholic extract of Ocimum sanctum (Os; 100 mg/kg; orally) or MK-801, an NMDA receptor antagonist (0.3 mg/kg; i.p.). In the rats subjected to only CRS, plasma cAMP level was significantly raised on day 21, with no significant change in plasma corticosterone level. There was a significant (p < 0.05) fall in myocardial glutathione level, along with a significant (p < 0.05) rise in myocardial superoxide dismutase (SOD) and catalase activities, while light microscopy showed evidence of myocardial edema. Both Os and MK-801 significantly prevented the CRS-induced rise in plasma cAMP level, myocardial SOD and catalase activities as well as the light microscopic changes in the myocardium. This study revealed that Ocimum sanctum protects rat heart from chronic restraint stress induced changes, through its central effect.

Administration, Oral↗

PubMed2006

Chimeric peptide of met-enkephalin and FMRFa: effect of chlorination on conformation and analgesia.

In our previous study YFa (YGGFMKKKFMRFa), a chimeric peptide of met-enkephalin and FMRFa, not only produced analgesia but also did not let the tolerance develop. In the continuation of the same study, Phe4 is chlorinated so as to assess the effect of chlorination on the conformation, lipophilicity and analgesia of chimeric peptide [p-Cl Phe(4)] YFa. Not only does the chlorination increase the lipophilicity but also enhances the propensity of [p-Cl Phe(4)] YFa to form alpha helix in comparison of YFa in presence of membrane mimicking solvent trifluoroethanol (TFE). This increase in lipophilicity and helix-forming ability results in more bioavailability and naloxone-reversible analgesia by [p-Cl Phe(4)] YFa. Though analgesia produced by [p-Cl Phe(4)] YFa is more than YFa at all doses, there is sudden decrease in analgesia at 45 and 60 min at 60 mg/kg. This sudden decrease of analgesia seems to be due to desensitization of opioid receptors.

Analgesia↗

PubMed2006

Contribution of genomics and proteomics in understanding the role of modifying factors in Parkinson's disease.

Parkinson's disease (PD) is a complex neurological disorder, characterized by selective degeneration of nigrostriatal dopaminergic neurons. It is a multi-factorial disease, contributed by a combination of age, genetic and environmental factors. Etiology of sporadic PD and mechanism underlying selective loss of dopaminergic neurons has not yet been clearly understood. Recent developments in genomics and proteomics have revolutionized the research on PD at genetic level. Differential gene expression patterns (DNA biochip technology), age-dependent complex genetic patterns (SNP genotyping), and protein expression profiles (proteomics) of PD patients have started providing the specific and rigorous molecular explanation and role of modifying factors in PD. Genomics and proteomics are further expected to help in developing biomarkers for diagnosis of early onset PD and also to develop valuable and potential therapeutic strategies for its treatment. In this review, we have discussed the progress made by genomics and proteomics, in understanding the role of modifying factors in PD.

Animals↗

PubMed2005

Expression of opioid receptor-like 1 (ORL1) & mu opioid receptors in the spinal cord of morphine tolerant mice.

BACKGROUND & OBJECTIVE: The mechanism underlying the development of tolerance to morphine is not clearly understood though a number of factors have been implicated. One of the likely factors may be increased activity of anti-opioid peptides like nociceptin (also known as orphanin FQ or N/OFQ). N/OFQ and morphine bind to opioid receptor-like 1 (ORL1) receptor and muopioid receptor respectively. The present work was undertaken to investigate the density of ORL1 and mu (mu) receptor expression in the spinal cord of mice after inducing morphine tolerance. METHODS: Swiss albino mice were injected with either morphine (experimental group, n=15) or saline (control, n=15), twice a day for 9 days. The development of tolerance was noted by the hotplate test. Cryostat sections of the cervical region of spinal cord were labeled with specific ligands to localize ORL1 and mu receptors. The density of receptor expression over laminae I-II of spinal cord was evaluated using image analysis system. RESULTS: The morphine treated mice developed tolerance by day 9 as evident by the hot plate test. Both receptors were selectively expressed at a higher concentration over the superficial laminae (I-II) of the dorsal horn, indicating a role in pain processing. An increased expression of ORL1 receptors was also noted over the gray matter around the central canal. Quantitative analysis showed an increased expression of ORL1 and mu receptors though the increase was not statistically significant. INTERPRETATION & CONCLUSION: The present study showed that both, ORL1 and mu-opioid receptors were expressed in areas of the spinal cord, concerned with transmission of pain signals. The density of these receptors increased in the superficial laminae (I-II) though not significantly from control after morphine tolerance. The increase in ORL1 receptors could oppose the analgesic action of morphine, contributing to tolerance. Further studies need to be done to elucidate the mechanism of morphine tolerance.

Animals↗

PubMed2004

Hepatoprotective effect of New Livfit, a polyherbal formulation, is mediated through its free radical scavenging activity.

The effect of New Livfit, a polyherbal formulation, was studied on pyrogallol-induced hepatotoxicity in rats. Administration of pyrogallol 100 mg/kg, i.p. caused a significant increase in liver enzymes as well as a significant increase in lipid peroxidation. Simultaneous administration of oral New Livfit and pyrogallol prevented these changes in hepatic damage. The results of the study showed that New Liv fi t(R) exerted a hepatoprotective effect against pyrogallol induced liver toxicity, which was mediated through its free radical scavenging property.

Animals↗

PubMed2004

Emblica officinalis causes myocardial adaptation and protects against oxidative stress in ischemic-reperfusion injury in rats.

The fruits of Emblica officinalis (Amla) are widely used in the Indian System of Medicine and are believed to increase defense against disease. In the present study, the effects of chronic oral administration of fresh fruit homogenate of Amla on: (i). myocardial antioxidant system and (ii). oxidative stress induced by ischemic-reperfusion injury (IRI) in rat heart were investigated. Fresh amla fruit homogenate, in three different doses (250, 500 and 750 mg/kg) and normal saline (C) were administered orally to Wistar albino rats (120-150 gms) of either sex daily for 30 days. There was reduction in basal myocardial lipid peroxidation, as evidenced by decreased thiobarbituric acid reactive substances (TBARS) level, and augmentation of myocardial endogenous antioxidants, like superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) in the treated rats. Hearts were also subjected to in vitro IRI (9 min of global ischemia, followed by 12 min of reperfusion, Langendorff's mode). Significant myocyte injury and rise in myocardial TBARS along with depletion of SOD, catalase, GSH (reduced glutathione) and GPx occurred in the control group. No significant increase in myocardial TBARS and depletion of antioxidant enzymes were observed in the treated groups. Myocyte injury was evident only in 250 mg/kg group. The results indicate that chronic Emblica officinalis administration causes myocardial adaptation by augmenting endogenous antioxidants and protects rat hearts from oxidative stress associated with ischemic-reperfusion injury.

Administration, Oral↗

PubMed2004

Current drug therapy of protozoal diarrhoea.

Protozoal infections of the gastrointestinal tract occur worldwide and have substantial morbidity and mortality. Prevalence is higher in the economically deprived regions of the world, especially the developing countries. Infections like amoebiasis and giardiasis have a worldwide distribution, being endemic in India. Apart from producing GI symptoms, growth and development of children is also impaired. It is seen that protozoa multiply rapidly in their hosts and as there is a lack of effective vaccines, chemotherapy has been the only practiced way to treat individuals and reduce transmission. The current treatment modalities for protozoal diarrhoea include 5-nitrosoimidazoles, iodoquinol, diloxanide furoate, paromomycin, chloroquine, and trimethoprim-sulphamethoxazole.

Age Distribution↗

PubMed2004

Zimmermann-Laband syndrome with bilateral developmental cataract - a new association?

An unusual case of Zimmermann-Laband syndrome in a young male child with an unreported association of bilateral developmental cataract is presented. The pathognomonic triad of gingival fibromatosis, aplastic or hypoplastic distal phalanges with absent nails, and enlargement of soft tissues of the face were obvious, besides the known moderate learning disability and mild hearing loss. The case is discussed in the light of relevant literature. To the best of our knowledge, this is the first report of early developmental cataracts in association with the Zimmermann-Laband syndrome. Besides detection and timely recognition of the syndrome to allow adequate dental care, ophthalmic screening at periodic intervals is merited to improve the overall quality of life for these patients.

Abnormalities, Multiple↗

PubMed2004

Modulation of antiepileptic effect of phenytoin and carbamazepine by melatonin in mice.

The pharmacokinetic and pharmacodynamic interaction of phenytoin and carbamazepine with melatonin was studied in a maximal electroshock seizure (MES) model in mice. The anticonvulsant ED(20), ED(33), ED(50) and ED(100) of phenytoin and carbamazepine, and ED(50) of melatonin were determined. Thereafter, the subanticonvulsant doses of phenytoin and carbamazepine were combined with ED(50) dose of melatonin. In combination with melatonin, 100% protection against seizures was achieved with phenytoin and carbamazepine in doses as low as ED(50) and ED(33), respectively. Serum levels of phenytoin and carbamazepine in animals that received ED(50) dose of phenytoin and carbamazepine per se, were not significantly different to those of the groups that received melatonin also. The study suggests that the synergistic antiepileptic effect is most likely a pharmacodynamic interaction, and not due to pharmacokinetic changes. Melatonin, thus, can be a potential adjunct to antiepileptic drugs, achieving a therapeutic effect at lower concentrations, hence limiting their dose-related toxicities.

Animals↗

PubMed2004

Antinociceptive effect of trans-resveratrol in rats: Involvement of an opioidergic mechanism.

trans-Resveratrol, a polyphenolic compound with potent antioxidant activity has recently been shown to be effective against carrageenan-induced hyperalgesia. In the present study, the effect of graded doses of trans-resveratrol was studied using a hot plate analgesiometer in rats. trans-Resveratrol at graded doses of 5, 10, 20 and 40 mg/kg i.p. produced dose-dependent analgesia. Pretreatment (20 min) with naloxone (1 mg/kg i.p.) blocked the analgesic effect. When the submaximal dose of trans-resveratrol (5 mg/kg i.p.) was combined with a submaximal dose of morphine (2 mg/kg i.p.), a potentiation effect was observed. The effect of trans-resveratrol (20 mg/kg i.p.) was also studied on morphine tolerance. Rats were divided into different groups: Group 1: morphine (10 mg/kg i.p.); Group 2: trans-resveratrol (5 mg/kg i.p.) administered 10 min before morphine (2 mg/kg i.p.); Group 3: trans-resveratrol (20 mg/kg i.p.) per se. Vehicle treated groups were run parallel. The treatment continued for 7 days. The occurrence of tolerance was estimated by comparing the antinociceptive effect of morphine with trans-resveratrol on day 1 and day 8. Both morphine and trans-resveratrol produced tolerance. However, in the group that received the combination of submaximal doses of trans-resveratrol and morphine, there was insignificant tolerance. These findings suggest that trans-resveratrol analgesia is mediated via an opioidergic mechanism and produces tolerance to its analgesic effect similar to morphine.

Analgesics↗

PubMed2004

Animal models of cerebral ischemia for evaluation of drugs.

Stroke is a major cause of death and disability worldwide. The resulting burden on the society continues to grow, with increase in the incidence of stroke. Brain attack is a term introduced to describe the acute presentation of stroke, which emphasizes the need for urgent action to remedy the situation. Though a large number of therapeutic agents like thrombolytics, NMDA receptor antagonists, calcium channel blockers and antioxidants, have been used or being evaluated, there remains a large gap between the benefits by these agents and properties an ideal drug for stroke should offer. In recent years much attention is being paid towards the exploration of herbal preparation, antioxidant agents and combination therapies including COX-2 inhibitors in experimental model of stroke. For better evaluation of the drugs and enhancement of their predictability from animal experimentation to clinical settings, it has been realized that the selection of animal models, the parameters to be evaluated should be critically assessed. Focal and global cerebral ischemia represents diseases that are common in the human population. Understanding the mechanisms of injury and neuroprotection in these diseases is important to learn new target sites to treat ischemia. There are many animal models available to investigate injury mechanisms and neuroprotective strategies. In this article we attempted to summarize commonly explored animal models of focal and global cerebral ischemia and evaluate their advantages and limitations.

Animals↗

PubMed2003

Neoral monitoring by limited sampling area under the concentration time curve in stable indian renal transplant recipients.

The optimization of cyclosporine (CsA) immunosuppression remains a challenge because of the narrow therapeutic window and highly variable pharmacokinetics (PK). The highly variable PK were improved by the introduction of the current microemulsion preparation Neoral. However, the best clinical benefit of this CsA microemulsion can only be obtained by regular PK monitoring. During the past decade, various PK strategies have been proposed, such as C(0), C(2), level monitoring, abbreviated or limited sampling approach, and various prediction algorithms to replace the conventional area under the curve (AUC). In this study we evaluated the Neoral PK in stable Indian renal transplant recipients using a limited sampling approach. The C(0) (mean +/- SE) was 175 +/- 15 ng. mL(-1); C(max) 970 +/- 101 ng. mL(-1), and the AUC (0-4) 2734 +/- 258 ng. h. mL(-1). The C(0) showed a poor relationship to AUC (0-4) (r =.65) but high correlations were obtained with C(2) (r = 0.93) and C(3) (r =.96). Our finding suggest that stable Indian renal transplant recipients should either be monitored using C(2) or C(3).

Area Under Curve↗

PubMed2003

Effect of Centella asiatica on pentylenetetrazole-induced kindling, cognition and oxidative stress in rats.

Cognitive impairment in epileptics may be a consequence of the epileptogenic process as well as antiepileptic medication. Thus, there is a need for drugs, which can suppress epileptogenesis as well as prevent cognitive impairment. In the present study, the effect of aqueous extract of Centella asiatica (CA) (100 and 300 mg/kg), an Indian medicinal plant known to possess antiepileptic, cognitive-enhancing and antioxidant property, was evaluated on the course of kindling development, kindling-induced learning deficit and oxidative stress markers in pentylenetetrazole (PTZ) kindled rats. Male Wistar rats were injected PTZ (30 mg/kg ip) once every alternate day (48+/-2 h) until the development of the kindling. Passive avoidance test and spontaneous locomotor activity were carried out 24 and 48 h after the last administration of PTZ, while the oxidative stress parameters (malondialdehyde [MDA] and glutathione) were carried out in the whole brain upon completion of the behavioral assessment. The administration of CA (300 mg/kg orally) decreased the PTZ-kindled seizures and showed improvement in the learning deficit induced by PTZ kindling as evidenced by decreased seizure score and increased latencies in passive avoidance behavior. However, low dose of the CA (100 mg/kg) showed improvement only in the learning deficit due to the kindling and failed to improve the seizure score. The findings suggest the potential of aqueous extract of CA as adjuvant to antiepileptic drugs with an added advantage of preventing cognitive impairment.

Animals↗

PubMed2003

Effect of alpha lipoic acid on intracerebroventricular streptozotocin model of cognitive impairment in rats.

In the present study, the effect of alpha lipoic acid, a potent free radical scavenger, was investigated against the intracerebroventricular streptozotocin model of cognitive impairment in rats, which is characterized by a progressive deterioration of memory, cerebral glucose and energy metabolism, and oxidative stress. Wistar rats were injected with intracerebroventricular streptozotocin bilaterally. The rats were treated chronically with alpha lipoic acid (50, 100 and 200 mg/kg) orally for 21 days starting from day 1 of streptozotocin injection in separate groups. The learning and memory behavior was evaluated and the rats were sacrificed for estimation of oxidative stress. The intracerebroventricular streptozotocin rats treated with alpha lipoic acid (200 mg/kg, p.o.) showed significantly less cognitive impairment as compared to the vehicle treated rats. There was also an insignificant increase in oxidative stress in the alpha lipoic acid treated groups. The study demonstrated the effectiveness of alpha lipoic acid in preventing cognitive impairment and oxidative stress induced by intracerebroventricular streptozotocin and its potential in dementia associated with age and age related neurodegenerative disorders where oxidative stress is involved such as Alzheimer's disease.

Animals↗

PubMed2003

Protective effect of exogenous administration of alpha-tocopherol in middle cerebral artery occlusion model of cerebral ischemia in rats.

Oxidative stress due to increased free radical generation and depletion of endogenous antioxidants have been implicated in ischemia-reperfusion-induced neuronal injury. The present study was carried out to study the effect of acute administration of alpha-tocopherol in the middle cerebral artery (MCA) occlusion model of stroke in rats. Rats were anesthetized using chloral hydrate (400 mg/kg i.p.) and subjected to 2 h of transient MCA occlusion. alpha-Tocopherol was administered at the dose of 125 and 250 mg/kg orally 1 h prior to the occlusion of MCA. Motor performance test (grip test, foot fault test, rotarod performance test, spontaneous locomotor activity), markers of oxidative stress and 2,3,5-triphenyl tetrazolium chloride staining were carried out 24 h after MCA occlusion. A vehicle-treated group was run parallel. It was observed that alpha-tocopherol at the dose of 125 mg/kg neither improved neurologic deficit, nor decreased the raised level of oxidative stress markers in comparison with the MCA-occluded rats. However, higher dose of alpha-tocopherol (250 mg/kg p.o.) afforded significant protection as evident by increase in motor performance tests and a decrease in the volume of infarction. The raised levels of malondialdehyde after MCA occlusion were also significantly attenuated. The results demonstrate that exogenous administration of alpha-tocopherol is able to reduce the neuronal damage caused during ischemia-reperfusion, which can be attributed to its antioxidant activity.

Administration, Oral↗

PubMed2003

Effect of antiemetic drugs on decrease in gastric emptying in experimental model of motion sickness in rats.

AIM: To study the effect of pretreatment with different antiemetic drugs on the motion sickness-induced inhibition in gastric emptying. METHODS: The rats were rotated for a period of 45 min at the rate of 30 rotations per min. RESULTS: Rotating the rats caused a significant decrease in gastric emptying as compared to the non-rotated group. Pretreatment with scopolamine (5 mg/kg, ip) did not reverse the delay in gastric emptying, while it per se caused inhibition of gastric emptying in the non-rotated group. Similarly other drugs mepyramine, cisapride, and granisetron did not have any effect on delay in gastric emptying caused by rotation. However beta blocker propranolol could partially but significantly reverse the decrease in gastric emptying. CONCLUSION: The present study demonstrated the potential use of propranolol as adjuvant with conventional antiemetics for motion sickness to combat associated secondary symptoms.

Animals↗

PubMed2003

Neuroprotective role of melatonin in oxidative stress vulnerable brain.

The brain is deficient in oxidative defense mechanisms and hence is at greater risk of damage mediated by reactive oxygen species (ROS) resulting in molecular and cellular dysfunction. Emerging evidence suggesting the activation of glutamate gated cation channels, may be another source of oxidative stress, leading to neuronal degeneration. Oxidative stress has been implicated in the development of neurodegenerative diseases like Parkinsonism, Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis, epileptic seizures, and stroke. Melatonin, the pineal hormone, acts as a direct free radical scavenger and indirect antioxidant. It is suggested that the increase in neurodegenerative diseases is attributable to a decrease in the levels of melatonin with age. Melatonin has been shown to either stimulate gene expression for the antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase) or to increase their activity. Additionally, it neutralizes hydoxyl radical, superoxide radical, peroxyl radical, peroxynitrite anion, singlet oxygen, hydrogen peroxide, nitric oxide, and hypochlorous acid. Unlike other antioxidants, melatonin can easily cross all morphophysiological barriers, e.g., the blood brain barrier, and enters cells and subcellular compartments. Though evidence are accumulating to suggest the potential of melatonin in neurodegenerative conditions, much information needs to be generated before the drug can find place in neurology clinics.

Animals↗

PubMed2002

Chronic treatment with trans resveratrol prevents intracerebroventricular streptozotocin induced cognitive impairment and oxidative stress in rats.

We have recently shown free radical generation is associated with cognitive impairment in intracerebroventricular (ICV) streptozotocin (STZ) model of sporadic dementia of Alzheimer's type in rats. Trans resveratrol is a polyphenolic compound and is known to have antioxidant activity. In the present study, the effect of trans resveratrol was investigated on ICV STZ induced cognitive impairment and oxidative stress in rats. Adult male Wistar rats were injected with ICV STZ bilaterally, on day 1 and day 3. The learning and memory behavior was assessed using passive avoidance paradigms, elevated plus maze and the closed field activity test while the parameters of oxidative stress assessed were malondialdehyde [MDA] and glutathione. The rats were treated with trans resveratrol chronically at doses of 10 and 20 mg/kg,i.p. for 21 days starting from day 1 of STZ injection. Trans resveratrol treatment significantly prevented ICV STZ induced cognitive impairment. There was a rise in brain glutathione and an insignificant increase in brain MDA in trans resveratrol treated ICV STZ rats as compared to significantly elevated brain MDA levels in the vehicle treated ICV STZ animals. The study demonstrates the effectiveness of trans resveratrol in preventing the cognitive deficits as well as the oxidative stress caused by ICV STZ in rats and it's potential in the treatment of neurodegenerative diseases such as Alzheimer's disease.

Animals↗