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Biomedical subjects

P Bhandari

Publications and source records attributed to P Bhandari.

At least 19 recordsLinked to original sources
PubMed2005

Mucosal expression of cyclooxygenase isoforms 1 and 2 is increased with worsening damage to the gastric mucosa.

AIMS: To test the hypothesis that both COX-1 and COX-2 expression in human gastric mucosa is up-regulated in the presence of inflammation as seen in patients with gastritis and gastric ulcers. METHODS AND RESULTS: We performed immunohistochemistry using COX-1 and COX-2 monoclonal antibodies on gastric biopsies from 59 patients with normal mucosa, gastritis and gastric ulcers. Expression of COX-1 and COX-2 was quantified using an intensity proportion scoring system. Expression of COX-1 was primarily seen in the lamina propria mononuclear cells with some expression in deep gastric glands in the ulcer group. Expression of COX-2 was primarily seen in the deep gastric glands with focal expression in the lamina propria mononuclear cells. We found a stepwise increase in the expression of both COX-1 and COX-2 as mucosal damage progressed from normal to gastritis to gastric ulcer. CONCLUSIONS: We conclude that both COX-1 and COX-2 expression in the gastric mucosa are increased in the setting of gastritis and gastric ulceration. Although this increased expression may be due, at least in part, to an increase in inflammatory cell numbers, this study raises the possibility that both COX-1 and COX-2 are inducible, contrary to the traditionally held view of only COX-2 being inducible.

Aged↗
PubMed2003

Cost-effectiveness of population screening for Helicobacter pylori in preventing gastric cancer and peptic ulcer disease, using simulation.

OBJECTIVES: To evaluate the cost-effectiveness of population screening for Helicobacter pylori in preventing gastric cancer and peptic ulcer disease in England and Wales. METHODS: A discrete event simulation model used parameter estimates, derived from peer-reviewed literature, routine data and statistical modelling. Population screening was compared with no screening but with opportunistic eradication in patients presenting with dyspepsia. Costs included screening, eradication and costs averted to provide costs per life years saved (cost/LYS) for preventing gastric cancer and peptic ulcer disease. Sensitivity analyses were undertaken. RESULTS: The cost/LYS from screening at age 40 years was Uk pounds 5860 at discount rates of 6%. The outcomes were sensitive to H. pylori prevalence, the degree of opportunistic eradication, the discount rate, the efficacy of eradication on gastric cancer risk, the risk of complicated peptic ulcer disease and gastric cancer associated with H. pylori infection, and the duration of follow-up. In sensitivity analyses, the cost/LYS rarely exceeded UK pounds 20000 over an 80-year follow-up, but did for shorter periods. CONCLUSIONS: H. pylori screening may be cost-effective in the long term. However, before screening can be recommended further evidence is needed to resolve some of the uncertainties, particularly over the efficacy of eradication on risk of gastric cancer, the risk associated with complicated peptic ulcers, and the effect of more widespread opportunistic testing of patients with dyspepsia.

Adult↗
PubMed2001

Studies on human colon cancer gene APC by targeted expression in Drosophila.

Mutations in human Adenomatous Polyposis Coli (APC) gene are associated with both familial and sporadic colorectal tumors. APC is known to down regulate beta-catenin levels, a transducer of Wnt signaling. The aim of this study is to provide transgenic Drosophila expressing either full-length or truncated forms of human APC (hAPC) protein and methods for using them in functional genomics and drug screening. Consistent with its biochemical properties, targeted expression of either full-length hAPC or its beta-catenin binding domain alone negatively regulated the function of the beta-catenin homologue, Armadillo (Arm) and thereby, inhibited Wnt/Wg signaling during fly development. hAPC inhibited Arm function even in the absence of GSK-3beta activity, although the latter was required to mediate the degradation of Arm. Consistent with this, hAPC suppressed the phenotypes induced by the over-expression of degradation-resistant forms of Arm. Subsequently, using hAPC-induced eye phenotypes as the assay in a suppressor-enhancer screen, we have identified two new loci in Drosophila, which modulate Wnt/Wg signaling. In addition, an anti-colon cancer drug, indomethacin, specifically enhanced hAPC-induced phenotypes.

Adenomatous Polyposis Coli Protein↗
PubMed1997

An Escherichia coli host strain useful for efficient overproduction of cloned gene products with NaCl as the inducer.

Salt-induced overexpression of genes cloned downstream of the phage T7 phi10 promoter was demonstrated in an Escherichia coli strain (GJ1158) which carries a single chromosomally integrated copy of the gene for phage T7 RNA polymerase under transcriptional control of the cis-regulatory elements of the osmoresponsive proU operon. Plasmids that have been constructed to obtain overproduction of individual target gene products in strain BL21(DE3) (by addition of isopropyl-beta-D-thiogalactopyranoside as an inducer) can directly be transformed into GJ1158. The NaCl induction regimen was also shown to be associated with a decreased propensity for sequestration of overexpressed target proteins within insoluble inclusion bodies.

Amino Acid Transport Systems↗
PubMed1993

Resinferatoxin, an ultrapotent capsaicin analogue, has anti-emetic properties in the ferret.

Resinferatoxin (100 micrograms/kg, s.c.), the ultrapotent analogue of capsaicin, when given acutely blocked radiation-(200 rads) and copper sulphate (40 mg% 30 ml, p.o.)-induced emesis in ferrets and substantially decreased loperamide (0.5 mg/kg, s.c.)-induced vomiting, without significantly affecting the von Bezold-Jarisch reflex or gag reflex. It also produced a decrease in core temperature as has been reported for capsaicin. The observation that resinferatoxin reduced or blocked emesis induced by both centrally (loperamide) and peripherally (CuSO4, radiation) acting stimuli suggests a novel anti-emetic action that may provide an insight into clinically useful innovative anti-emetics. The mechanism by which resinferatoxin has its anti-emetic effect is at present unknown, although the combination of results from the present study suggest a central site of action involving modulation of release of neurotransmitter, possibly in the nucleus tractus solitarius.

Animals↗
PubMed1993

Modification in sucrose tolerance test with acarbose, guargum and their combination in patients with non-insulin dependent diabetes.

The study was undertaken to assess the efficacy guargum, Acarbose and their combination in modifying the sucrose absorption in patients of non Insulin dependent diabetes mellitus (NIDDM). Fifty patients of NIDDM were randomly distributed in three groups. Group A had 20 patients who received 20 grams of guargum, Group B had 10 patients who received 100 mg of Acrabose, Group C had 20 patients who received 10 grams of guargum and 50 grams of Acrabose. All the patients underwent 50 grams sucrose tolerance test with and without the trial drugs. Blood glucose levels were determined at 0, 30, 60, 90 and 120 minutes after sucrose loading. With the drugs, there was a significant decrease in the blood glucose levels at all time intervals (p < 001) in all the three groups. In all the three groups the blood glucose levels with the trial drugs was significantly lower (p < 001) than without the drug. It was seen that acarbose alone and guargum alone did not differ significantly in reducing the blood sugar level whereas combination of two produced significantly greater reduction in blood glucose levels than either of the drug used alone. Thus both guargum and acarbose are equally effective in modifying the absorption of sucrose. When combined in half the dosage they have synergistic effect and the reduction in blood glucose level is greater than either of the drug used alone.

Acarbose↗
PubMed1992

The neuropharmacology of loperamide-induced emesis in the ferret: the role of the area postrema, vagus, opiate and 5-HT3 receptors.

Loperamide, an opiate receptor agonist, commonly used in the treatment of diarrhoea, reliably induced emesis in the ferret, when given subcutaneously. The response latency was short (less than 10 min) and the emesis lasted for approx 70 min. The dose-response curve for the emetic response was "bell-shaped" and all animals responded at 0.5 mg/kg but none at 5 mg/kg (s.c.). The response was unaffected by dopamine D2 receptor antagonism (domperidone 1.0 mg/kg, s.c.) or 5-HT3 receptor antagonism (granisetron or ondansetron 1.0 mg/kg, s.c.). The onset of the response was delayed for about 60 min by naloxone or naloxone methiodide (1.0 mg/kg, s.c.) and abolished by naloxanazine (1.0 mg/kg, s.c.), reported to be relatively selective for mu receptors. The results implicate mu receptors (possibly mu 1) in the induction of emesis by loperamide and provide some support for activation of opiate receptors also having anti-emetic effects, as suggested in previous studies. The emetic response to loperamide was unaffected by abdominal vagotomy but was abolished by ablation of the area postrema, indicating that loperamide-induced emesis may be used as a test for ablation of the area postrema in studies of the emetic mechanism in the ferret.

Animals↗
PubMed1992

Are all 5-HT3 receptor antagonists the same?

A number of 5-HT3 receptor antagonists are currently in clinical development as antiemetics. In this paper we focus on two of these antagonists, granisetron and ondansetron, and compare their antimetic activity against cisplatin (10 mg/kg i.v.)- or whole body X-irradiation (200 rads)-induced emesis in the conscious ferret. The results presented here have been discussed in the light of the recently published literature. Our data suggest that in comparison to ondansetron, granisetron is a more potent, longer acting and pharmacologically "cleaner" compound with a more conventional dose-response profile. The possible impact of these features upon the performance of these compounds in the clinic is discussed particularly with respect to dosing regimens and clinical efficacy. Differences appear to be emerging between granisetron and ondansetron in both these respects, although a direct head-to-head clinical comparison has yet to be carried out. This would involve studies monitoring a sufficiently high number of patients receiving severely emetogenic regimes to allow real clinical differences to be detected with the appropriate statistical power.

Animals↗
PubMed1991

Preliminary evidence for the involvement of the putative 5-HT4 receptor in zacopride- and copper sulphate-induced vomiting in the ferret.

Previous studies of the mechanism of zacopride-induced emesis in ferrets have concluded that it is mediated predominantly by an antagonist effect on 5-HT3 receptors although the possibility of a contribution from an agonist effect at 5-HT4 receptors was not excluded. This study shows that zacopride (200 micrograms/kg p.o.)-induced emesis can be blocked by a 'high dose' (1000 micrograms/kg) of ICS205930 but not by a low dose (100 micrograms/kg) or by 'high doses' (1000 micrograms/kg) of another more selective 5-HT3 receptor antagonist granisetron. As ICS205930, at high doses, is reported to be a 5-HT4 receptor antagonist it appears likely that activation of 5HT4-receptors contributes to emesis induced by zacopride. 'High' doses of ICS205930, but not granisetron or ondansetron, can also block the vagally mediated emesis induced by oral CuSO4 suggesting that 5-HT4 receptors involved in emesis are closely associated with abdominal vagal afferents.

Analysis of Variance↗
PubMed1989

Effect of intracerebroventricular administration of angiotensin II on emetic reflex in dogs.

Area postrema is rich in angiotensin II receptors and intravenous (iv) administration of angiotensin II has been reported to elicit emesis. However, in the present study intracerebroventricular (icv) administration of angiotensin II up to a dose of 10 micrograms failed to elicit emesis. It is suggested that presence of a cerebrospinal fluid-brain barrier in area postrema most probably prevents access of icv angiotensin II to its receptors which are otherwise accessible on iv administration.

Angiotensin II↗
PubMed1989

Role of endogenous opioids and histamine in morphine induced emesis.

The role of opioid and histaminergic system in morphine induced emesis was investigated in dogs. Morphine (25 micrograms, icv) consistently evoked emesis with an average latency of 195 +/- 29 sec which was fully accounted for by an action on the chemoreceptor trigger zone (CTZ) as its ablation rendered animals refractory to vomiting. Intraventricular pretreatment with opioid antagonist naloxone, histamine H1 antagonist mepyramine and H2 antagonists metiamide and cimetidine afforded protection to icv morphine emesis. The CSF histamine concentration was significantly raised 5 min after icv morphine administration. The results suggest that both endogenous opioid and histamine are involved in morphine emesis. Naloxone in high doses (1600 micrograms, icv) elicited emesis which was not blocked by CTZ ablation confirming our earlier report.

Animals↗