Fate of swallowed interleukin 8 and TNFα, and effect on the Wistar rat gut

To evaluate the passage of cytokines through the gastrointestinal tract, we investigated the digestion of interleukin-8 (IL-8) and tumour necrosis factor α (TNFα), in vitro and in vivo, and their propensity to induce intestinal inflammation. We serially immuno-assayed IL-8 and TNFα solutions co-incubated with each of three pancreatin preparations at pH 4.5 and pH 8. We gavaged IL-8, TNFα and marker into 15 Wistar rats, and measured their faecal cytokine concentrations by ELISA and histologically examined their guts. IL-8 immunoreactivity was extinguished by all pancreatin preparations after 1 h of incubation at 37 °C. TNFα concentration progressively fell from 1 to 4 h with all enzyme preparations. Buffer control samples maintained their cytokine concentrations throughout incubation. No IL-8 or TNFα was detected in any rat faecal pellets. There was no significant proinflammatory effect of the gavaged cytokines on rat intestine. IL-8 and TNFα in aqueous solution could well be fully digested in the CF gut when transit time is normal and exogenous enzymes are provided, although cytokines swallowed in viscous sputum may be protected from such digestion

Marked increase in proton pump inhibitors use in Australia

Objectives: To examine the trends in the prescribing of subsidised proton pump inhibitors (PPIs) and histamine receptor antagonists (H2RAs), in the Australian population from 1995 to 2006 to encourage discussion regarding appropriate clinical use. PPIs and H2RAs are the second highest drug cost to the publicly subsidised Pharmaceutical Benefits Scheme (PBS). Design: Government data on numbers of subsidised scripts, quantity and doses for PPIs and H2RAs were analysed by gender and age, dose and indication. Main outcome measure: Drug utilisation as DDD [defined daily dose]/1000 population/day. Results: The use of combined PPIs increased by 1318%. Utilisation increased substantially after the relaxation of the subsidised indications for PPIs in 2001. Omeprazole had the largest market share but was substituted by its S-enantiomer esomeprazole after its introduction in 2002. There was considerable use in the elderly with the peak use being in those aged 80 years and over. The utilisation of H2RAs declined 72% over 12 years. Conclusions: PPI use has increased substantially, not only due to substitution of H2RAs but to expansion in the overall market. Utilisation does not appear to be commensurate with prevalence of gastro-oesophageal reflux disease (GORD) nor with prescribing guidelines for PPIs, with significant financial costs to patients and PBS. This study encourages clinical discussion regarding quality use of these medicines. © 2010 John Wiley & Sons, Ltd.

Drugs and the gastrointestinal tract

16.1. Agents to control acidity 16.1.1 Antacids 16.1.2 Proton pump inhibitors and antibiotics for Helicobacter pylori 16.1.3 Histamine H2 receptor antagonists 16.1.4 Misoprostol 16.1.5 Sucralfate 16.2. Prokinetics and emetics 16.2.1 Introduction to prokinetics 16.2.2 Prokinetic agents 16.2.3 Emesis with cytotoxic drugs and drugs for 16.2.4 Motion sickness and drugs for 16.2.5 Drugs for post-operative emesis 16.3. Agents used for diarrhea, constipation, irritable bowel syndrome 16.3.1 Treatment for diarrhea 16.3.2 Treatment for constipation 16.3.3 Treatment for opioid-induced constipation 16.4. Drugs for inflammatory bowel disease 16.4.1 Mesalazine 16.4.2 Glucocorticoids 16.4.3 Infliximab