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Biomedical subjects

I L Beales

Publications and source records attributed to I L Beales.

At least 19 recordsLinked to original sources

Efficacy of Helicobacter pylori eradication therapies: a single centre observational study.

BACKGROUND: Many Helicobacter pylori eradication regimens have been described. There are little data reporting their efficacy or integration in routine clinical practice. The overall results of eradication therapy in a cohort of patients are described and an algorithm for management outlined. METHODS: 469 patients receiving eradication therapy in routine clinical practice were evaluated. The successes of individual regimes as first, second and third line therapy were determined. RESULTS: Overall success after one, two and three courses of therapy were 73% (95% confidence intervals 69-77%), 94% (91-96%) and 98% (97-99%) respectively. 10 different regimens, including many non-recommended ones were used as primary therapy. Ranitidine bismuth citrate-amoxicillin-clarithromycin triple therapy (94.8%, 90-99%) was significantly more effective than any other combination as primary therapy, including all proton pump inhibitor based triple therapies. Quadruple therapy with bismuth chelate-proton pump inhibitor-tetracycline and a nitroimidazole (70%, 52-88%) and ranitidine bismuth citrate-based triple therapy (73%, 56-90%) where more effective second line combinations than proton pump inhibitor-triple therapies (37.5%, 12-58%). Third line therapy directed by the results of sensitivity testing improved eradication compared to further empirical antibiotics. The use of a proton pump inhibitor with clarithromycin and a nitroimidazole as initial therapy was associated with a significantly worse overall eradication rate than other combinations. CONCLUSIONS: Helicobacter pylori eradication rates can be maximised by using ranitidine bismuth citrate-clarithromycin-amoxicillin containing triple therapy, followed by bismuth and nitroimidazle containing second-line therapy, with third line combinations directed by sensitivity testing. Proton pump inhibitor-clarithromycin-metronidazole combinations should be avoided.

Anti-Bacterial Agents↗

Effect of platelet-activating factor on gastrin release from cultured rabbit G-cells.

Gastric infection with Helicobacter pylori is associated with hypergastrinemia. Platelet activating factor (PAF) is produced in H. pylori-infected mucosa. The effects of PAF on gastrin release from cultured antral rabbit G cells were examined. Rabbit antral G-cells were obtained by collagenase-EDTA digestion and enriched by centrifugal elutriation. After 40 hr in culture, gastrin release in response to PAF was assessed. PAF stimulated gastrin release in a dose-dependent manner. A maximal release of 67% above basal was seen with PAF at 100 nM. PAF also enhanced the gastrin release stimulated by forskolin and bombesin. PAF-stimulated gastrin release was abolished by a PAF-receptor antagonist. Gastrin release stimulated by PAF was abolished by chelation of intra- or extracellular calcium or the L-type calcium channel inhibitor verapamil as well as by the protein kinase C inhibitor chelerythrine. Platelet-activating factor may contribute to the hypergastrinemia of H. pylori infection by stimulating gastrin release from G cells. PAF-stimulated gastrin release involves influx of extracellular calcium via L-type channels and activation of protein kinase C.

Animals↗

Inhibition of carbachol stimulated acid secretion by interleukin 1beta in rabbit parietal cells requires protein kinase C.

BACKGROUND: Interleukin 1beta (IL-1beta) is a potent inhibitor of gastric acid secretion. Regulatory actions at several levels have previously been demonstrated, including direct inhibition of parietal cell acid secretion. Although IL-1beta may activate several intracellular signalling pathways, the mechanisms responsible for inhibition of carbachol stimulated acid secretion have not been determined. AIMS: To investigate the roles of protein kinase C (PKC) and the sphingomyelinase signalling pathways in the regulation of acid secretion by IL-1beta. METHODS: Rabbit parietal cells were obtained by collagenase-EDTA digestion and centrifugal elutriation. Acid secretion stimulated by carbachol and A23187 (to mimic elevations in intracellular calcium) was assessed by 14C aminopyrine uptake in response to IL-1beta, PKC, and sphingomyelinase manipulation. RESULTS: IL-1beta inhibited carbachol and A23187 stimulated acid secretion in a dose dependent manner. The inhibitory actions were completely reversed by each of three different PKC inhibitors, staurosporine, H-7, and chelerythrine, as well as by PKC depletion with high dose phorbol ester pretreatment. IL-1beta did not downregulate parietal cell muscarinic receptor. IL-1beta significantly increased membrane PKC activity. Activation of the sphingomyelinase/ceramide pathway had no effect on basal or stimulated acid secretion. The inhibitory action of IL-1beta was independent of protein kinase A and protein kinase G activity. CONCLUSIONS: IL-1beta directly inhibits parietal cell carbachol stimulated acid secretion. This action occurs distal to muscarinic receptor activation and elevations in intracellular calcium and requires PKC.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Helicobacter pylori increases gastrin release from cultured canine antral G-cells.

OBJECTIVE: To investigate the mechanisms underlying the hypergastrinaemia of Helicobacter pylori by examining the effects of H. pylori on basal and stimulated gastrin release from cultured canine G-cells. METHODS: Canine antral G-cells were prepared by collagenase-EDTA digestion and cultured for 40 h. G-cells were then cultured for a further 24 h with two different H. pylori sonicates before basal and bombesin-stimulated gastrin release were measured by radioimmunoassay. RESULTS: Treatment of G-cells with both H. pylori sonicates significantly enhanced basal gastrin release (by 17-27%) and bombesin-stimulated gastrin release (by 115-133%). This effect was independent of cagA and vacuolating cytotoxin status. Control treatment with Escherichia coli sonicate had no effect on gastrin release. There was no change in the cellular content of gastrin. CONCLUSIONS: Incubation of antral G-cells with H. pylori constituents enhances subsequent basal and bombesin-stimulated gastrin release. Direct contact between H. pylori and G-cells in the gastric antrum may be responsible for the hypergastrinaemia seen with the infection.

Animals↗

Effect of PACAP-27 on 14C-aminopyrine accumulation in isolated rabbit parietal cells.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is present in gastric mucosa, but its direct effect on parietal cells is unknown. We examined this using 14C-aminopyrine uptake in elutriated rabbit cells. PACAP-27 had no effect on basal cells but significantly increased the response to histamine (10(-4) M) at 10(-9) M and to carbachol (10(-4) M) in the presence of ranitidine (10(-4) M) at 10(-7) M and 10(-8) M. PACAP (6-38), an antagonist of PACAP, inhibited the effect of PACAP-27 on carbachol-stimulated cells. Vasoactive intestinal peptide had no significant effect. In conclusion, PACAP-27 has a direct additive effect on stimulated rabbit parietal cells in vitro.

Aminopyrine↗

Soybean agglutinin stimulated cholecystokinin release from cultured rabbit jejunal cells requires calcium influx via L-type calcium channels.

We have studied the mechanism of soybean agglutinin (SBA) mediated cholecystokinin (CCK) release in enriched cultured cholecystokinin-secreting cells. 12-O-Tetradecanoylphorbol-13-acetate 1 mM significantly stimulated release of CCK-like-immunoreactivity (CCK-LI) by 55%+/-17% (p < 0.05), which was blocked by the protein kinase C inhibitor staurosporine 100 nM. Forskolin 10 mM stimulated CCK-LI by 82%+/-12% (p < 0.05) and this was inhibited by somatostatin 1 nM. 1-Phenylalanine 20 mM and Bay K 8644 1 mM stimulated CCK-LI by 69%+/-22% and 60%+/-19% respectively (p < 0.05), these responses were completely abolished by the L-type calcium channel antagonist verapamil 10 mM. SBA 10 and 100 microg/ml stimulated CCK-LI by 65%+/-22% and 74%+/-24% respectively (p < 0.05). The effect of SBA was inhibited by verapamil and N-acetylgalactosamine. We conclude that SBA stimulates CCK-LI through calcium flux via L-type calcium channels.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗