Effect of Aspirin and ibuprofen either alone or in combination on gastric mucosa and bleeding time and on serum prostaglandin E and thromboxane A levels in the anaesthetized rats in vivo.

There is much evidence that a combination of ibuprofen (IBU) and Aspirin (ASA) can antagonize the irreversible inhibition of platelet function. This study was designed to investigate the degree of gastric damage, bleeding time (BT) and fluctuations in the serum levels of prostaglandin E (PGE) and thromboxane A (TXA) after oral administration of ASA (200 mg/kg) and IBU (50 mg/kg) either alone or in combination in rats in vivo. The stomach was assessed for any damage either after 6 h, 18 h or 6 days and carboxymethylcellulose (1% CMC) served as a vehicle and control.

Altered physiology of acid secretion in depression-prone Flinders rats results in exacerbated NSAID and stress-induced gastric damage.

Background: Flinders Sensitive Line (FSL) rats are characterized by hypersensitivity to cholinergic stimuli and have been extensively used for studying depressive disorders. A link between depression and peptic ulcers has long been established; however, there is a lack of data from animal models.

Methods: We studied the physiology of acid secretion in FSL and Flinders Resistant Line (FRL) rats in vivo and in vitro.

Spontaneous autoimmune gastritis and hypochlorhydria are manifest in the ileitis-prone SAMP1/YitFcs mice.

SAMP1/YitFcs mice serve as a model of Crohn's disease, and we have used them to assess gastritis. Gastritis was compared in SAMP1/YitFcs, AKR, and C57BL/6 mice by histology, immunohistochemistry, and flow cytometry. Gastric acid secretion was measured in ligated stomachs, while anti-parietal cell antibodies were assayed by immunofluorescence and enzyme-linked immunosorbent spot assay.

Association of myocardial infarctions with COX-2 inhibition may be related to immunomodulation towards a Th1 response resulting in atheromatous plaque instability: an evidence-based interpretation.

Cyclooxygenase (COX) inhibitors remain a major class of drugs in rheumatology and their widespread use is expected to continue. The view that a prothrombotic effect explains the increase in myocardial infarction (MI) associated with both COX-2 selective and traditional NSAIDs (tNSAIDs) has been increasingly questioned. We review the evidence that prostanoids direct the immune response away from a Th1 response and that consequently inhibition of prostaglandin synthesis results in augmentation of the Th1 response by limiting prostanoid synthesis.

The effect of CYP2C19 polymorphisms on H. pylori eradication rate in dual and triple first-line PPI therapies: a meta-analysis.

Premise: It has been suggested that proton pump inhibitor (PPI)-related differences in Helicobacter pylori eradication rates are partly because of CYP2C19 polymorphisms and there have been conflicting data in this area. We conducted a meta-analysis to investigate the evidence relating CYP2C19 to first-line H. pylori eradication rates.

Peptic ulcer disease today.

Over the past few decades, since the introduction of histamine H(2)-receptor antagonists, proton-pump inhibitors, cyclo-oxygenase-2-selective anti-inflammatory drugs (coxibs), and eradication of Helicobacter pylori infection, the incidence of peptic ulcer disease and ulcer complications has decreased. There has, however, been an increase in ulcer bleeding, especially in elderly patients. At present, there are several management issues that need to be solved: how to manage H.

Host-specific differences in the physiology of acid secretion related to prostaglandins may play a role in gastric inflammation and injury.

Immune mediators are involved in strain-specific manifestations of Helicobacter pylori infection, and the type of immune response is associated with production of PGE(2), which in turn influences gastric acid secretion. Acid secretion plays a pivotal role, not only in the pattern of H. pylori-induced gastritis and its consequences, but also in nonsteroidal anti-inflammatory drug (NSAID)-induced gastropathies.

Establishment of T-Helper-2 immune response based gerbil model of enteric infection.

Background: The reciprocal antagonism of T-helper-1 (Th-1) and Th-2 type immune responses suggests that helminth parasitic infection may ameliorate disease where a Th-1 type response dominates. The Mongolian gerbil has been useful in the investigation of the pathogenesis of gastric cancer, since long-term infection of gerbils with Helicobacter pylori induces adenocarcinoma. In this study the kinetics of worm expulsion and associated immune responses in gerbils infected with Trichinella spiralis were investigated in an attempt to establish an animal model of parasitic infection that could be helpful when investigating the effect of a Th-2 type response on Th-1-based intestinal disorders.

Effect of Th1 cytokines on acid secretion in pharmacologically characterised mouse gastric glands.

Background And Aims: Acid secretion plays an important role in the ecology of Helicobacter species and acid secretory status heralds patterns of gastritis. The presence of inflammatory cells and their products, in close proximity to parietal cells, questions the extent of the effect of cytokines on acid secretion.

Methods: We adopted and extensively characterised the mouse gastric gland preparation and its secretory capacity, which was measured using (14)C-aminopyrine accumulation.

Effect of purified lipopolysaccharides from strains of Helicobacter pylori and Helicobacter felis on acid secretion in mouse gastric glands in vitro.

As a bacterial product, Helicobacter pylori lipopolysaccharide (LPS) can originate in close proximity to parietal cells, but the role of this uniquely structured endotoxin on acid secretion has not been fully investigated and remains unclear. The purpose of this study was to test the direct effect of purified LPS (tested range, 0.1 to 100 microg/ml) from various strains of H.

Therapeutic effects of the endothelin receptor antagonist Ro 48-5695 in the TNBS/DNBS rat model of colitis.

Objective: Endothelins can act as polyfunctional cytokines. It is therefore possible that endothelins could play an active role in gut inflammation. Elevated levels of endothelin-1 have been reported in ulcerative colitis and Crohn's disease.

Anti-ulcerogenic properties of endothelin receptor antagonists in the rat.

Background: Endothelins have been implicated in gastric mucosal damage in a variety of animal models. Exogenous ET-1 and ET-3 are causally associated with experimental gastric ulcers. Furthermore, clinical reports also show elevated plasma and gastric mucosal endothelin-1 levels in patients suffering from peptic ulcers.

Inhibitory effect of diazepam on human natural killer activity in vitro.

The in vitro effect of diazepam on natural killer (NK) cell activity isolated from human peripheral blood has been investigated. NK cell function was estimated by means of a radioactive chromium (51Cr) assay in which human erythroleukaemia K562 cells were used as the target. Diazepam suppressed NK cell function in a concentration-dependent manner (10(-7)-10(-5) M) and a positive correlation was found between the dose of diazepam and inhibition detected by percentage killing of K562 cells.

Immunomodulatory properties of diazepam-binding inhibitor: effect on human interleukin-6 secretion, lymphocyte proliferation and natural killer cell activity in vitro.

We have examined the influence of diazepam binding inhibitor (octadecaneuro-peptide, DBI33-50) on cell mediated immune responses including LPS-stimulated monocyte IL-6 secretion, PHA induced lymphocyte proliferation and NK cell function in humans. All studies were performed in vitro on isolated human peripheral blood mononuclear cells in the absence or presence of synthetic DBI33-50. It has been shown that DBI33-50, in concentration between 10(-6)-10(-8) M, enhances the LPS-induced secretion of IL-6, as determined by specific bioassay for this monokine.

Immunomodulatory activities of the somatostatin analogue BIM 23014c: effects on murine lymphocyte proliferation and natural killer activity.

We have examined the effect of somatostatin and its octapeptide analogue BIM 23014c on concanavalin A-induced lymphocyte proliferation and target-specific natural killer activity both in vitro and in vivo. Using Peyer's patches and spleen as a source of lymphocytes, we found that both peptides modulated immunity in a dose-dependent manner. Comparatively, there was no significant difference between the activity of somatostatin or BIM 23014c in the modulation of immunity.

Selective modulation of the natural killer activity of murine intestinal intraepithelial leucocytes by the neuropeptide substance P.

Neuropeptides can influence immune effector cell function at both systemic and mucosal immune sites. We examined the ability of substance P (SP) to modulate the natural killer (NK) activity of intestinal intraepithelial leucocytes (IEL). Yac-1 killing by IEL but not splenic cells was increased after either 18 hr preincubation or 6 hr of co-incubation with SP.