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G Kaur

Publications and source records attributed to G Kaur.

At least 37 records · Page 2Linked to original sources
PubMed2001

Investigations on possible serotonergic involvement in effects of OB-200G (polyherbal preparation) on food intake in female mice.

BACKGROUND: OB-200G is a polyherbal preparation containing aqueous extracts of Garcinia cambogia, Gymnema sylvestre, Zingiber officinale, Piper longum and resin from Commiphora mukul, all possessing thermogenic properties. Our previous studies reveal OB-200G to exert antiobesity effects in dietary animal models of obesity. AIM OF THE STUDY: The present study investigated the possible involvement of serotonergic system in the effect of OB-200G on food intake. We examined the effects of systemic pretreatment with 5-HT depletor, p-chlorophenylalanine (PCPA, 300 mg/kg, i. p. for 6 days), 5-HT1A agonist, (8-hydroxy-2-(di-N-propylamino)-tetralin (8-OH-DPAT, 0.1 mg/kg, i. p.), nonselective 5-HT antagonist, cyproheptadine (1 mg/kg, i. p.), 5-HT2 receptor antagonist, seganserin (1 and 2 mg/kg, i. p.) and 2-deoxy-D-glucose (2-DG, glucose antimetabolite, 500 mg/kg, i. p.) on satiety induced by OB-200G (500 mg/kg, p. o.) in non-deprived female mice. The results were compared with fluoxetine (10 mg/kg, i. p.), a selective serotonin reuptake inhibitor. METHODS: Fifteen minutes after the last drug administration, groups of mice were presented with sweetened chow and the amount of food consumed was recorded at 0.5,1,2, 3 and 4h time intervals. RESULTS: The hyperphagic effect of PCPA, 8-OH-DPAT, cyproheptadine and 2-DG was significantly (p < 0.05) antagonized by both OB-200G and fluoxetine. However, the anorectic effect of fluoxetine was not reversed by centrally acting 5-HT2 antagonist, seganserin but the latter markedly attenuated the satiety action of OB-200G. CONCLUSION: The present observations suggest the role of serotonin in mediation of satiety by OB-200G and hence its antiobesity effect.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2001

Role of cholinergic and GABAergic neurotransmission in the opioids-mediated GnRH release mechanism of EBP-primed OVX rats.

The effect of intracerebroventricular administration of mu-opioid agonist, morphine (a drug of potential abuse), and its antagonist, naloxone, followed by morphine was studied on the metabolism of acetylcholine and gamma amino butyric acid in seven discrete regions of brain from EBP-primed ovariectomized rats. We also assayed serum luteinizing hormone and follicle stimulating hormone after morphine and naloxone + morphine treatments. Cholineacetyltransferase and acetylcholinesterase, gamma-aminobutyric acid transaminase, succinic semialdehyde dehydrogenase and glutamate dehydrogenase activities were found to decrease significantly in hypothalamic as well as other brain regions studied. Naloxone given prior to morphine injection was seen to reverse the effect of morphine on enzymes activities. Our study provides evidence that opioidergic modulation of GnRH release is mediated through cholinergic and GABAergic neurotransmission besides monoaminergic control and the results may further help to elucidate the basis of neuronal dysfunction in opiate addicts.

Acetylcholinesterase↗
PubMed2001

Molecular diversity of HLA-A*02 in Asian Indians: predominance of A*0211.

The North Indians are considered predominantly Caucasoid with an admixture of genes from the Mongoloid and Aryan races. The present study was undertaken to investigate the genetic diversity of HLA-A*02 in the North Indian population and determine the frequency distribution of its molecular subtypes at the population level. The study revealed a high occurrence of A*0211 (33.8%) in this population along with increased frequencies of the common Oriental alleles, A*0206 (7.5%) and A*0207 (32.5%) and also of HLA-A*0205 (15%) commonly observed in negroid populations. HLA-A*0211 has only been reported with very low frequencies among the Ticuna Jews, Thai population, and Colombian Blacks in the malaria endemic areas of Africa. Significantly, we observed an unexpectedly low frequency of A*0201 (3.8%) in contrast to its distribution in Western Caucasians in whom it constitutes 95% of the HLA-A2 repertoire. Prevalence of HLA-A*0211 at very high frequencies among North Indians may be a consequence of the founder effect, racial admixture or selection pressure due to environmental factors in this population.

Amino Acid Sequence↗
PubMed2001

Subchronic studies on modulation of feeding behavior and body weight by neurosteroids in female mice.

Neurosteroids have shown promising therapeutic potential in a wide variety of neuropsychiatric and cognitive disorders. However, little research has been done on their role for the treatment of eating disorders and regulation of energy balance in the body. In the present study, subchronic treatment with the neuroactive steroid progesterone (10 mg/kg s.c.) for 28 days produced significant increases in body weight and elicited marked hyperphagia as compared to a vehicle-treated control group at all time intervals as observed on days 1, 7, 14, 21 and 28. On the other hand, subchronic treatment with dehydroepiandrosterone sulfate (DHEAS) for 28 days at 10 mg/kg s.c. produced significant (p < 0.05) decreases in body weight and food intake at all time intervals on days 1, 7, 14 and 28 suggesting that decreases in food intake are responsible for the reduction of body weight caused by DHEAS in this strain of female mice. Subchronic treatment with DHEAS (10 mg/kg s.c.) also significantly (p < 0.05) suppressed progesterone-induced weight gain and hyperphagia as compared to the progesterone-treated group but not as compared to the vehicle-treated control group (except on day 1). In conclusion, the results of the present study suggest that progesterone-induced hyperphagia and weight gain can serve as a useful animal model of drug-induced obesity. The drugs useful in this model may have implications for the treatment of obesity caused by disturbances of ovarian hormone secretion in females. Furthermore, the study underscores the use of these neurosteroids for the treatment of eating disorders.

Animals↗
PubMed2001

RNA damage and inhibition of neoplastic endothelial cell growth: effects of human and amphibian ribonucleases.

Angiogenesis defines the many steps involved in the growth and migration of endothelial cell-derived blood vessels. This process is necessary for the growth and metastasis of tumors, and considerable effort is being expended to find inhibitors of tumor angiogenesis. This usually involves screening of potential anti-angiogenic compounds on endothelial cells. To this end, two candidate anti-angiogenic RNA-damaging agents, onconase and (-4)rhEDN, were screened for their effects on endothelial cell proliferation using three distinct types of endothelial cells in culture: HPV-16 E6/E7-immortalized human umbilical vein endothelial cells (HUVECs), a Kras-transformed HPV-16 E6/E7 HUVEC (Rhim et al., Carcinogenesis 4, 673-681, 1998), and primary HUVECs. Onconase similarly inhibited proliferation in all three cell lines (IC(50) = 0.3-1.0 microM) while (-4)rhEDN was more effective on immortalized HUVEC cell lines (IC(50) = 0.02-0.06 microM) than on primary HUVECs (IC(50) > 0.1 microM). Differential sensitivity to these agents implies that more than one endothelial cell type must be used in proliferation assays to screen for novel anti-angiogenic compounds.

Angiogenesis Inhibitors↗
PubMed2001

Differential effect of polyherbal, antiobesity preparation, OB-200G in male and female mice and monosodium glutamate-treated rats.

Effect of administration of different doses (0.25, 0.5, 1 and 2 g/kg, twice daily, po) of a polyherbal preparation, OB-200G and fluoxetine (10 mg/kg, ip) for 21 days was studied on food intake and body weight in male and female Laka mice. The study further investigated the effect of administration of 0.5 g/kg dose of OB-200G for 40 days on body weight, fat pad weights, locomotor activity and biochemical parameters in monosodium glutamate (MSG)-treated male and female Wistar rat pups. Administration of OB-200G produced dose dependent decrease in body weight in both male and female mice. On the other hand, fluoxetine decreased body weight only in female mice. The food intake was significantly (P < 0.05) increased in both fasted male and female mice after treatment with the lower dose (0.25 g/kg, po) of OB-200G. However, significant (P < 0.05) decrease in food intake was recorded with the administration of higher doses (0.5, 1 and 2 g/kg, po) of OB-200G and fluoxetine in fasted female mice on day 1, 7, 14 and 21. But in male mice differential effect on food intake was recorded at different doses on day 1, 7, 14 and 21. Further, OB-200G administration significantly (P < 0.05) decreased body weight and fat pad weights, increased serum glucose levels and ambulatory activity in MSG-treated female rats but not in MSG-treated male rats. The results suggest that OB-200G involves gender differences in mediating its antiobesity effect and may supplement the current armamentarium for the treatment of obesity.

Adipose Tissue↗
PubMed2000

Opioid regulation of gonadotropin release: role of signal transduction cascade.

The present investigation elucidates the opioidergic modulation of gonadotropin releasing hormone release mechanism by signal transduction cascade in discrete brain regions from estrogen-progesterone primed ovariectomized rats. The effects of mu-opioid agonist morphine and its antagonist naloxone followed by morphine were studied (in two different groups of rats) on protein kinase A, adenosine 3',5' cyclic monophosphate, protein kinase C and calcium/calmodulin protein kinase-II as well as phospholipase C, phospholipase A(2), diacylglycerol and inositol 1,4, 5-triphosphate. Significant decline in phosphoinositide metabolism was observed after morphine treatment as depicted by decrease in phospholipase C and phospholipase A2 activities as well as inositol 1,4,5-triphosphate and diacylglycerol contents from discrete brain regions. Protein kinase A activity showed translocation from membrane bound to cytosolic form along with a decrease in its activator adenosine 3',5'-cyclic monophosphate levels in morphine-treated group. Calcium/calmodulin dependent protein kinase II activity also declined, whereas, protein kinase C activity increased in the cytosolic fraction after 45 min of morphine administration. Naloxone was seen to counteract the changes induced by morphine in most of the brain regions studied. Morphine also suppressed luteinizing hormone levels, whereas, follicle stimulating hormone level did not change. The present investigation provides evidence for opioidergic mediated suppression of gonadotropin release through the downregulation of signal transduction cascade.

Animals↗
PubMed2000

Enzymatic oxidant and antioxidants of human blood platelets in unstable angina and myocardial infarction.

In ischaemic heart conditions we report a remarkable increase in platelet xanthine oxidase activity and rise in the levels of malondialdehyde (MDA) with concomitant decrease in the activities of free radical scavenging enzymes - superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. The increased levels of free radical generating system and MDA and lowered levels of free radical scavenging systems seem to have critical role in ischaemic heart conditions.

Angina, Unstable↗
PubMed2000

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

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

Alprazolam↗
PubMed2000

Effects of the bcr/abl kinase inhibitors AG957 and NSC 680410 on chronic myelogenous leukemia cells in vitro.

The tyrphostin AG957 (NSC 654705) inhibits p210bcr/abl, the transforming kinase responsible for most cases of chronic myelogenous leukemia (CML). The present studies were performed to determine the fate of AG957-treated cells and assess the selectivity of AG957 for CML myeloid progenitors. When K562 cells (derived from a patient with blast crisis CML) were treated with AG957, dose- and time-dependent p210bc/abl down-regulation was followed by mitochondrial release of cytochrome c, activation of caspase-9 and caspase-3, and apoptotic morphological changes. These apoptotic changes were inhibited by transfection with cDNA encoding dominant negative caspase-9 but not dominant-negative FADD or blocking anti-Fas antibodies. In additional experiments, a 24-h AG957 exposure caused dose-dependent inhibition of K562 colony formation in soft agar. To extend these studies to clinical samples of CML, peripheral blood mononuclear cells from 10 chronic phase CML patients and normal controls were assayed for the growth of hematopoietic colonies in vitro in the presence of increasing concentrations of AG957. These assays demonstrated selectivity of AG957 for CML progenitors, with median IC50s (CML versus normal) of 7.3 versus >20 microM AG957 in granulocyte colony-forming cells (P < 0.001), 5.3 versus >20 microM in granulocyte/macrophage colony-forming cells (P < 0.05), and 15.5 versus > 20 microM in erythroid colony-forming cells (P > 0.05). The adamantyl ester of AG957 (NSC 680410) down-regulated p210bcr/abl in K562 cells and inhibited granulocyte colony formation in CML specimens at lower concentrations without enhanced toxicity in normal progenitors. These observations not only demonstrate that AG957-induced p210bcr/abl down-regulation is followed by activation of the cytochrome c/Apaf-1/caspase-9 pathway but also indicate that this class of kinase inhibitor exhibits selectivity worthy of further evaluation.

Adamantane↗
PubMed2000

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

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

Animals↗
PubMed2000

Influence of PGRs on carbohydrate content in Lipaphis erysimi (Kalt.).

Six compounds (IBA, chlorogenic acid, cytokinine, GA3, alar B-9 and maleic hydrazide) belonging to four different categories of plant growth hormones were used to study their effect on carbohydrate content in L. erysimi. The second instar nymphs (48 hr old) were given both dipping and leaf surface treatment with 1024 ppm concentration of compounds for two time intervals i.e. 48 and 96 hr. The carbohydrate content decreased after treatment with 4 of the plant growth regulators i.e. GA3, alar B-9, IBA and chlorogenic acid with maximum suppression in GA3 treatment. Cytokinine did not induce any derogatory influence on carbohydrate content. The treatment with maleic hydrazide, on the other hand enhanced the carbohydrate content. It could be concluded that the application of these PGRs affected the carbohydrate synthesis or metabolism.

Animals↗
PubMed2000

Conservative management of malocclusion in mixed dentition.

The treatment planning in mixed dentition period has changed from extraction to non extraction. Any orthodontic treatment must take into consideration the growth trends and the pubertal growth spurt. The two cases presented here were treated during mixed dentition period in different ways: one with fixed appliances and the other with removable myofunctional appliance therapy, with satisfactory results. Hence for a conservative treatment approach, the non-extraction treatment is recommended in mixed dentition period.

Child↗
PubMed2000

Pharmacokinetics, urinary excretion and dosage regimen of diminazene in crossbred calves.

The pharmacokinetics, urinary excretion and dosage regimen of diminazene were investigated in crossbred male calves following a single intramuscular dose (3.5 mg x kg-1). Following intramuscular administration, the pharmacokinetics of diminazene was described with a one-compartment open model. The absorption rate constant and absorption half-life were 9.86 +/- 3.06 h-1 and 0.121 +/- 0.40 h, respectively. The value of elimination half-life was 107.5 +/- 8.50 h. The apparent volume of distribution was 0.74 +/- 0.07 L x kg-1. Systemic availability following intramuscular administration was 91.7%. Approximately 65% of the administered dose of diminazene was eliminated in the urine within 24 h of its intramuscular administration. Diminazene was bound to plasma proteins to the extent of approximately 32%. The satisfactory intramuscular dosage regimen of diminazene for calves would be 2.24 mg x kg-1 followed by 1.5 mg x kg-1 at 7 days.

Animals↗
PubMed1999

Antitumor benzothiazoles. 8. Synthesis, metabolic formation, and biological properties of the C- and N-oxidation products of antitumor 2-(4-aminophenyl)benzothiazoles.

2-(4-Aminophenyl)benzothiazoles 1 and their N-acetylated forms have been converted to C- and N-hydroxylated derivatives to investigate the role of metabolic oxidation in the mode of action of this series of compounds. 2-(4-Amino-3-methylphenyl)benzothiazole (1a, DF 203, NSC 674495) is a novel and potent antitumor agent with selective growth inhibitory properties against human cancer cell lines. Very low IC(50) values (<0.1 microM) were encountered in the most sensitive breast cancer cell lines, MCF-7 and T-47D, whereas renal cell line TK-10 was weakly inhibited by 1a. Cell lines from the same tissue origin, MDA-MB-435 (breast), CAKI-1 (renal), and A498 (renal), were insensitive to 1a. Accumulation and metabolism of 1a were observed in sensitive cell lines only, with the highest rate of metabolism occurring in the most sensitive MCF-7 and T-47D cells. Thus, differential uptake and metabolism of 1a by cancer cell lines may underlie its selective profile of anticancer activity. A major metabolite in these sensitive cell lines has been identified as 2-(4-amino-3-methylphenyl)-6-hydroxybenzothiazole (6c). Hydroxylation of 1a was not detected in the homogenate of previously untreated MCF-7, T-47D, and TK-10 cells but was readily observed in homogenates of sensitive cells that were pretreated with 1a. Accumulation and covalent binding of [(14)C]1a derived radioactivity was observed in the sensitive MCF-7 cell line but not in the insensitive MDA-MB-435 cell line. The mechanism of growth inhibition by 1a, which is unknown, may be dependent on the differential metabolism of the drug to an activated form by sensitive cell lines only and its covalent binding to an intracellular protein. However, the 6-hydroxy derivative 6c is not the 'active' metabolite since, like all other C- and N-hydroxylated benzothiazoles examined in this study, it is devoid of antitumor properties in vitro.

Aniline Compounds↗
PubMed1999

Identification of cytosolic aldehyde dehydrogenase 1 from non-small cell lung carcinomas as a flavopiridol-binding protein.

The synthetic flavone flavopiridol can be cytostatic or cytotoxic to mammalian cells, depending on the concentration of the drug and the duration of exposure. It has been shown to inhibit the cyclin-dependent kinase (CDK) family of cell cycle regulatory enzymes. However, the existence of additional potential targets for drug action remains a matter of interest to define. To identify cellular targets, flavopiridol was immobilized. CDKs, particularly CDK 4, bound weakly to immobilized flavopiridol when ATP was absent but not in its presence. Two proteins with molecular weights of 40 kDa and 120 kDa had high affinities to the immobilized flavopiridol independent of the presence of ATP. They were present in all cell lines analyzed: cervical (HeLa), prostate and non-small cell lung carcinoma (NSCLC) cell lines. A 60-kDa protein, which was present only in NSCLC cells and bound similarly well to immobilized flavopiridol, was identified as cytosolic aldehyde dehydrogenase class 1 (ALDH-1). The level of this protein correlated with the resistance of NSCLC cell lines to cytotoxicity caused by 500 nM flavopiridol but not higher flavopiridol concentrations. Despite binding to ALDH-1, there was no inhibition of dehydrogenase activity by flavopiridol concentrations as high as 20 microM and flavopiridol was not metabolized by ALDH-1. The results suggest that high cellular levels of ALDH-1 may reduce cytotoxicity of flavopiridol and contribute to relative resistance to the drug. This is the first report that flavopiridol binds to proteins other than CDKs.

Aldehyde Dehydrogenase↗