Interrelationships of ion transport in rat submaxillary duct epithelium

The transport of Na+, K+, Cl-, and HCO3(-) across the epithelium of the rat submaxillary salivary duct is postulated to be due to the coupling of the basolateral Na+-K+-ATPase with various ion transport systems in the luminal and basolateral membranes. Na+ reabsorption depends on the presence of a rheogenic (Na+ conductance) and an electroneutral (Na+:H exchange) pathway, both of which are sensitive to amiloride. K+ secretion is postulated to be mediated by a K+: H+ antiport, coupling between Na+ reabsorption and K+ secretion, thus depending on local H+ ion concentration. The ratio between electroneutral Na+ influx and K+ efflux, therefore, determines the rate of HCO3(-) secretion. In the absence of Na+ influx, although K+ efflux falls, HCO3(-) secretion rises to a value equal to that of K+ secretion. The maintenance of K+ secretion in the absence of luminal Na+ requires an additional Na+-entry step across the basolateral membrane, also postulated to be due to Na+:H+ exchange.     

Fulminant ulcerative colitis despite maximal immunosuppression following liver transplantation: A case report and literature review

Inflammatory Bowel Disease (IBD) is thought to be the result of an overly aggressive immune response to ubiquitous antigens. Immuno -modulation and -suppression is therefore currently the treatment of choice. It was long anticipated that the course of pre-existing IBD should improve after orthotopic liver transplantation (OLT) due to increased immunosuppression. We report the case of a patient who developed acute fulminant colitis despite triple immunosuppression and mesalazine and review the relevant literature.     

The role of aspirin in post-polypectomy bleeding – a retrospective survey

Background

Keratins 8/18 (K8/K18) are established hepatoprotective proteins and K8/K18 variants predispose to development and adverse outcome of multiple liver disorders. The importance of K8/K18 in alcoholic liver disease as well as in established cirrhosis remains unknown.

Methods

We analyzed the K8 mutational hot-spots in 261 prospectively followed-up patients with alcoholic cirrhosis (mean follow-up 65 months). PCR-amplified samples were pre-screened by denaturing high-performance liquid chromatography and conspicuous samples were sequenced.

Results

67 patients developed hepatocellular carcinoma (HCC) and 133 died. Fourteen patients harbored amino-acid-altering K8 variants (5xG62C, 8xR341H). The presence of K8 variants did not associate with development of HCC (log-rank=0.5) or death (log-rank=0.7) and no significant associations were obtained for the single K8 variants after a correction for multiple testing was performed.

Conclusions

Keratin variants are expressed in a low percentage of patients with alcoholic cirrhosis and do not influence HCC development. Further studies conducted in larger prospective cohorts are needed to find out whether presence of K8 R341H variant predispose to non-HCC-related liver mortality.

     

Somatostatin and Octreotide Stimulate Short-Circuit Current in Human Colonic Epithelium

In vitro somatostatin is a potent inhibitor of intestinal ion secretion in animal models and cultured human cell lines, providing a rationale for its use in secretory diarrheas. However, the effects of somatostatin on ion transport in native human colonic epithelium have not been reported. In this study the effects of somatostatin and octreotide on the basal short-circuit current and the cAMP- and Ca²⁺-stimulated short-circuit current were studied in isolated human colonic mucosa mounted in Ussing chambers. Under basal conditions somatostatin and octreotide (1 mol/liter) stimulated a small, bumetanide-sensitive increase in short-circuit current. Following stimulation of secretion with prostaglandin E₂, somatostatin and octreotide further increased the short-circuit current in a dose dependent fashion (ED₅₀ 10 nmol/liter for both). This stimulation of short-circuit current was not affected by pretreatment of the tissue with basolateral tetrodotoxin (1 mol/liter) or mucosal amiloride (10 mol/liter). In contrast, somatostatin and octreotide had no effect when secretion was stimulated with 8-bromo-cAMP, and pretreatment of the tissue with somatostatin and octreotide (0.1 mol/liter) did not alter the secretory response to carbachol. The absence of any inhibitory effect of somatostatin and octreotide on electrogenic secretion in the human colon may explain the variable results obtained when somatostatin or octreotide are used for the treatment of secretory diarrheas.     

Omeprazole therapy decreases the need for dilatation of peptic oesophageal strictures

BACKGROUND: Better control of gastric acid secretion with omeprazole appeared to decrease the need for dilatation of oesophageal strictures complicating gastro-oesophageal reflux disease in our hospital-based endoscopy service. AIM: To investigate whether the perceived decrease in the need for oesophageal dilatation could be documented from endoscopy records, and, if confirmed, whether this could be related to the treatment used. PATIENTS AND METHODS: Retrospective study of the records of 69 patients who had peptic oesophageal strictures dilated, followed by treatment with acid inhibition for at least 6 months. Mean duration of follow-up was 3.9 years during treatment with H2-receptor antagonists and 2.1 years while on omeprazole (258 and 78 patient-years, respectively). Re-dilatation rates were compared between those treated with H2-receptor antagonists or omeprazole. RESULTS: There has been a significant decrease in dilatations performed for gastro-oesophageal reflux induced strictures (P<0.001), while dilatation rates for other indications remained constant. Treatment with omeprazole not only decreased the need for further dilatations, but also prolonged the mean time between any further dilatations to 26.3 months compared to 9.3 months for those on an H2-receptor antagonist (P<0.0001). CONCLUSIONS: Following dilatation of peptic oesophageal strictures, treatment with omeprazole in place of an H2-blocker significantly decreases the need for repeat dilatation.