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Gastric Ulceration (gastric + ulceration)
Selected AbstractsEffect of trefoil factors on the viscoelastic properties of mucus gelsEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 7 2002L. Thim Abstract Background Trefoil peptides (TFFs) are expressed and secreted in a tissue-specific manner in the gastrointestinal tract. Evidence of coexpression of trefoil peptides and mucins has been demonstrated in most mucus-producing cells in the gastrointestinal tract. The expression of trefoil peptides is up-regulated in gastric ulceration and colitis. It is believed that TFF peptides interact with mucin to increase viscosity but this has never been confirmed. The aims of the present study were to elucidate the direct effect of trefoil peptides on mucus gel formation. Materials and methods The viscosity of mucin solutions was measured by means of a rotational rheometer after adding three mammalian trefoil peptides: TFF1, TFF2, and TFF3. Results Adding TFF2 (0·3%) to the mucin solutions (8%) resulted in more than a factor 10 increase in viscosity and elasticity, and the mucin solution was transformed into a gel-like structure with serpentine-like complexes between the mucin and TFF2. The dimer form of TFF3 also increased viscosity but resulted in a spider's web-like structure. The monomer forms of TFF1 and TFF3 had very little effect on the viscosity and elasticity of the mucin solutions. Conclusions The addition of TFF2 to mucin solutions results in significantly increased viscosity and elasticity, under which the mucin solutions are transformed into a gel-like state. The ability of some trefoil peptides to catalyse the formation of stable mucin complexes may be one of the ways by which these peptides exert their protective and healing functions. [source] Deficits in spatial learning and synaptic plasticity induced by the rapid and competitive broad-spectrum cyclooxygenase inhibitor ibuprofen are reversed by increasing endogenous brain-derived neurotrophic factorEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2003Kendra N. Shaw Abstract Cyclooxygenase (COX), which is present in two isoforms (COX1 and 2), synthesizes prostaglandins from arachidonic acid; it plays a crucial role in inflammation in both central and peripheral tissues. Here, we describe its role in synaptic plasticity and spatial learning in vivo via an effect on brain-derived neurotrophic factor (BDNF) and prostaglandin E2 (PGE2; both measured by Elisa). We found that broad-spectrum COX inhibition (BSCI) inhibits the induction of long-term potentiation (LTP; the major contemporary model of synaptic plasticity), and causes substantial and sustained deficits in spatial learning in the watermaze. Increases in BDNF and PGE2 following spatial learning and LTP were also blocked. Importantly, 4 days of prior exercise in a running wheel increased endogenous BDNF levels sufficiently to reverse the BSCI of LTP and spatial learning, and restored a parallel increase in LTP and learning-related BDNF and PGE2. In control experiments, we found that BSCI had no effect on baseline synaptic transmission or on the nonhippocampal visible-platform task; there was no evidence of gastric ulceration from BSCI. COX2 is inhibited by glucorticoids; there was no difference in blood corticosterone levels as measured by radioimmunoassay in any condition. Thus, COX plays a previously undescribed, permissive role in synaptic plasticity and spatial learning via a BDNF-associated mechanism. [source] Diazoxide, a KATP opener, accelerates restitution of ethanol or indomethacin-induced gastric ulceration in rats independent of polyaminesJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 3 2001M Rahgozar Abstract Background and Aims: Experimental acute gastric ulcerations (EAGU) are healed very rapidly. This healing process has two steps; mucosal restitution and delayed repair. Adenosine 5,-triphosphate (ATP)-dependent potassium channels (KATP) have a regulatory role in the gastrointestinal physiology. In the present study, the effects of KATP channel modulators; diazoxide (channel opener) and glibenclamide (channel antagonist) on the healing of EAGU were investigated. The effect of polyamine (mediators presumably responsible for restitution) biosynthesis by difluoromethylornithine (DFMO) on diazoxide-induced alterations, and the effects of acid secretion inhibitors (cimetidine, omeprazole and atropine) on the mucosal restitution of EAGU were also studied. Methods: Groups of 10 male rats were starved for 24 h and EAGU was induced by oral administration of 1 mL 60% ethanol or a subcutaneous injection of 30 mg/kg indomethacin. Different groups were subjected to various doses of diazoxide (5, 15, 45 mg/kg) and/or glibenclamide (2, 6, 18 mg/kg) administered intraperitoneally (i.p.) after EAGU induction. Polyamine biosynthesis was inhibited by a single i.p. injection of DFMO (500 mg/kg), administered 10 min before EAGU induction. Cimetidine, omeprazole or atropine were administered intraperitoneally at doses of 200, 5 and 1 mg/kg, respectively, after EAGU induction. Animals were killed and their gastric mucosa was examined for ulcerations. Results: Diazoxide accelerated the healing of EAGU, whereas glibenclamide aggravated EAGU. The concomitant administration of glibenclamide antagonized the diaoxide effect. Diazoxide-induced acceleration of mucosal restitution was not abolished by DFMO. Cimetidine, omeprazole and atropine had no effect on the healing of EAGU. Conclusion: The KATP channels may play an important role in the gastric mucosal restitution independent of polyamines. Acid inhibition cannot reverse EAGU. [source] Clinical care and technical recommendations for 90yttrium microsphere treatment of liver cancerJOURNAL OF MEDICAL IMAGING AND RADIATION ONCOLOGY, Issue 3 2010S-C Wang Summary Selective internal radiation therapy (SIRT) with 90yttrium microspheres is a relatively new clinical modality for treating non-resectable malignant liver tumours. This interventional radiology technique employs percutaneous microcatheterisation of the hepatic arterial vasculature to selectively deliver radioembolic microspheres into neoplastic tissue. SIRT results in measurable tumour responses or delayed disease progression in the majority of eligible patients with hepatocellular carcinoma or hepatic metastases arising from colorectal cancer. It has also been successfully used as palliative therapy for non-colorectal malignancies metastatic to the liver. Although most adverse events are mild and transient, SIRT also carries some risks for serious and , rarely , fatal outcomes. In particular, entry of microspheres into non-target vessels may result in radiation-induced tissue damage, such as severe gastric ulceration or radiation cholecystitis. Radiation-induced liver disease poses another significant risk. By careful case selection, considered dose calculation and meticulous angiographic technique, it is possible to minimise the incidence of such complications to less than 10% of all treatments. As the number of physicians employing SIRT expands, there is an increasing need to consolidate clinical experience and expertise to optimise patient outcomes. Authored by a panel of clinicians experienced in treating liver tumours via SIRT, this paper collates experience in vessel mapping, embolisation, dosimetry, microsphere delivery and minimisation of non-target delivery. In addition to these clinical recommendations, the authors propose institutional criteria for introducing SIRT at new centres and for incorporating the technique into multidisciplinary care plans for patients with hepatic neoplasms. [source] Preclinical pharmacology of robenacoxib: a novel selective inhibitor of cyclooxygenase-2JOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2009J. N. KING This manuscript reports the results of preclinical studies in the rat with robenacoxib, a novel selective cyclooxygenase (COX)-2 inhibitor. Robenacoxib selectively inhibited COX-2 in vitro as evidenced from COX-1:COX-2 IC50 ratios of 27:1 in purified enzyme preparations and >967:1 in isolated cell assays. Binding to COX-1 was rapid and readily reversible (dissociation t1/2 << 1 min), whilst COX-2 binding was slowly reversible (t1/2 = 25 min). In vivo, robenacoxib inhibited PGE2 production (an index of COX-2 inhibition) in lipopolysaccharide (LPS)-stimulated air pouches (ID50 0.3 mg/kg) and for at least 24 h in zymosan-induced inflammatory exudate (at 2 mg/kg). Robenacoxib was COX-1 sparing, as it inhibited serum TxB2 synthesis ex vivo (an index of COX-1 inhibition) only at very high doses (100 mg/kg but not at 2,30 mg/kg). Robenacoxib inhibited carrageenan-induced paw oedema (ID50 0.40,0.48 mg/kg), LPS-induced fever (ID50 1.1 mg/kg) and Randall,Selitto pain (10 mg/kg). Robenacoxib was highly bound to plasma protein (99.9% at 50 ng/mL in vitro). After intravenous dosing, clearance was 2.4 mL/min/kg and volume of distribution at steady-state was 306 mL/kg. Robenacoxib was preferentially distributed into inflammatory exudate; the AUC for exudate was 2.9 times higher than for blood and the MRT in exudate (15.9 h) was three times longer than in blood (5.3 h). Robenacoxib produced significantly less gastric ulceration and intestinal permeability as compared with the reference nonsteroidal anti-inflammatory drug (NSAID), diclofenac, and did not inhibit PGE2 or 6-keto PGF1, concentrations in the stomach and ileum at 30 mg/kg. Robenacoxib also had no relevant effects on kidney function at 30 mg/kg. In summary, results of preclinical studies in rats studies suggest that robenacoxib has an attractive pharmacological profile for potential use in the intended target species, cats and dogs. [source] Antiinflammatory and antiulcer properties of tannins from Myracrodruon urundeuva Allemão (Anacardiaceae) in RodentsPHYTOTHERAPY RESEARCH, Issue 3 2007S. M. C. Souza Abstract Myracrodruon urundeuva Allemão is a plant utilized in Northeast Brazil as an antiinflammatory, wound healing and in gynecological illnesses. The objectives of the present study were to evaluate the antiinflammatory and antiulcer properties of the tannin-enriched fraction (TEF) isolated from the stem bark of M. urundeuva, in the formalin test, in mice, and in carrageenan-induced paw edema and gastric ulcer models, in rats. The results showed that TEF dose-dependently inhibited both phases of the formalin test. However, the effect was predominant in the 2nd phase of the response where inhibitions of 47%, 76% and 85% were observed, with doses of 5, 10 and 50 mg/kg, i.p. In the carrageenan-induced paw edema, significant inhibitions were observed at 3 h (44%) and 4 h (28%), with a dose of 10 mg/kg, i.p. TEF also significantly decreased by 37%, 43% and 57% gastric ulceration induced by indomethacin, at doses of 10, 20 and 50 mg/kg p.o. In the ethanol-induced gastric ulcer model, TEF was less effective, and significant inhibitions (42% to 46%) were observed only with doses of 100 and 200 mg/kg, p.o., respectively. In conclusion, it was shown that TEF presents antiinflammatory and antiulcer effects, partly due to its antioxidant action, known to be present in polyphenols, including tannins. Copyright © 2006 John Wiley & Sons, Ltd. [source] Is cytochrome P450 2C9 genotype associated with NSAID gastric ulceration?BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 6 2001Jennifer H. Martin Aims, The aim of this study was to explore whether genetic variation of cytochrome P450 2C9 (CYP2C9) contributes to NSAID-associated gastric ulceration. The hypothesis tested was that CYP2C9 poor metabolizer genotype would predict higher risk of gastric ulceration in patients on NSAIDs that are metabolized by CYP2C9, due to higher plasma NSAID concentrations. Methods, Peripheral blood DNA samples from 23 people with a history of gastric ulceration attributed to NSAIDs metabolized by CYP2C9, and from 32 people on NSAIDs without gastropathy, were analysed to determine CYP2C9 genotype. Results, The following genotypes were found: *1/*1 (wild type) in 70% of cases and 58% of controls, *1/*2 in 17% of cases and 29% of controls, *1/*3 in 13% of cases and 13% of controls. The difference between case and control nonwild-type genotype frequency was 11.5% (95% CI ,14,37%), with the direction of the difference being against the hypothesis. No individuals with homozygote poor metaboliser genotype were identified. The differences in genotype frequencies between the two groups were not significant and the frequencies were similar to those in a large published population study. Ninety-five percent binomial confidence interval analysis confirms that there is no apparent clinically significant relationship between CYP2C9 genotype and risk of gastric ulceration although a small difference in risk in poor metabolizers cannot be excluded. Conclusions, These results do not support the hypothesis that gastric ulceration resulting from NSAID usage is linked to the poor metabolizing genotypes of CYP2C9. [source] MELATONIN PROTECTS AGAINST HYDROGEN PEROXIDE-INDUCED GASTRIC INJURY IN RATSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 4 2009Ahmed M Mohamadin SUMMARY 1Melatonin (MT) is a pineal hormone that is also abundant in the gut and has a well known role in scavenging oxygen free radicals. The aim of the present study was to evaluate the potential protective effects of MT against H2O2 -induced gastric lesions in rats. 2An experimental model of gastric ulceration was established in rats using 15% H2O2. Melatonin (12.5, 25 or 50 mg/kg, intagastrically) was administered to rats 30 min before H2O2 challenge. 3Intragastric administration of H2O2 resulted in haemorrhagic lesions in the fundic area of the stomach. Furthermore, H2O2 induced gastric oxidative stress, as indicated by depletion of reduced glutathione (GSH), inhibition of glutathione peroxidase (GPx) activity and elevation of malonedialdehyde (MDA) levels. These effects were accompanied by decreased gastric tissue levels of prostaglandin (PG) E2 and nitric oxide (NO), as well as increased levels of tumour necrosis factor (TNF)-,. Administration of MT (12.5, 25 or 50 mg/kg) 30 min before H2O2 significantly attenuated the development of gastric lesions in a dose-dependent manner. The protective effects of MT were accompanied by significant inhibition of the H2O2 -induced reduction in gastric content of GSH and GPx activity and elevation in MDA levels. Furthermore, MT antagonized H2O2 -induced reduction of gastric PGE2 and NO levels and elevation of TNF-,. 4In conclusion, MT protects rat gastric mucosa against H2O2 -induced damage. The observed protective effects of MT can be attributed, at least in part, to its anti-oxidant properties, preservation of PGE2 and NO levels, as well as inhibition of TNF-, induction in gastric tissues. [source] Diazoxide, a KATP opener, accelerates restitution of ethanol or indomethacin-induced gastric ulceration in rats independent of polyaminesJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 3 2001M Rahgozar Abstract Background and Aims: Experimental acute gastric ulcerations (EAGU) are healed very rapidly. This healing process has two steps; mucosal restitution and delayed repair. Adenosine 5,-triphosphate (ATP)-dependent potassium channels (KATP) have a regulatory role in the gastrointestinal physiology. In the present study, the effects of KATP channel modulators; diazoxide (channel opener) and glibenclamide (channel antagonist) on the healing of EAGU were investigated. The effect of polyamine (mediators presumably responsible for restitution) biosynthesis by difluoromethylornithine (DFMO) on diazoxide-induced alterations, and the effects of acid secretion inhibitors (cimetidine, omeprazole and atropine) on the mucosal restitution of EAGU were also studied. Methods: Groups of 10 male rats were starved for 24 h and EAGU was induced by oral administration of 1 mL 60% ethanol or a subcutaneous injection of 30 mg/kg indomethacin. Different groups were subjected to various doses of diazoxide (5, 15, 45 mg/kg) and/or glibenclamide (2, 6, 18 mg/kg) administered intraperitoneally (i.p.) after EAGU induction. Polyamine biosynthesis was inhibited by a single i.p. injection of DFMO (500 mg/kg), administered 10 min before EAGU induction. Cimetidine, omeprazole or atropine were administered intraperitoneally at doses of 200, 5 and 1 mg/kg, respectively, after EAGU induction. Animals were killed and their gastric mucosa was examined for ulcerations. Results: Diazoxide accelerated the healing of EAGU, whereas glibenclamide aggravated EAGU. The concomitant administration of glibenclamide antagonized the diaoxide effect. Diazoxide-induced acceleration of mucosal restitution was not abolished by DFMO. Cimetidine, omeprazole and atropine had no effect on the healing of EAGU. Conclusion: The KATP channels may play an important role in the gastric mucosal restitution independent of polyamines. Acid inhibition cannot reverse EAGU. [source] | ||||||||||