Effect of caffeine on the human small intestine

Methylxanthines produce intracellular accumulation of cyclic 3'5'-AMP (cAMP) by inhibition of phosphodiesterase and mucosal cAMP accumulation. Cyclic AMP is thought to mediate small intestinal secretion caused by some enterotoxins, hormones, and methylxanthines. These studies were designed to evaluate the effect of caffeine on small intestinal net fluid movement and transit times. The administration of caffeine in amounts ordinarily contained in many beverages and medications (75 to 300 mg) resulted in striking net secretion in the jejunum which lasted at least 15 minutes. This occurred in six of seven studies. Baseline net absorption of 0.5 ml per cm per hr was reversed to net secretion of 6.0 +/- 2.2 ml per cm per hr after oral caffeine ingestion (P less than 0.01). Net secretion also occurred in the ileum in seven of eight studies, but the onset of secretion appeared 35 min later than in the jejunum. These patterns of secretion correlated best with the passage of the intestinal bolus of caffeine rather than plasma caffeine levels. In contrast to other net secretory conditions, which increase the speed of transit, small intestinal transit times, as determined by dye dilution methods, were unchanged by caffeine. It is possible that methylxanthine-induced small intestinal secretion may play a role in the symptoms experienced by some patients with functional diarrhea.     

Cloning and localization of RPE65 mRNA in salamander cone photoreceptor cells1

RPE65 is a potential retinoid-processing protein expressed in the retinal pigment epithelium. Mutations in the RPE65 gene have been shown to cause certain inherited retinal dystrophies. Previous studies have shown that salamander cone photoreceptor cells have a unique retinoid processing mechanism which is distinct from that of rods. To determine whether RPE65 is expressed in photoreceptors, the RPE65 cDNA was cloned from a salamander retinal cDNA library. The deduced protein consists of 533 amino acids and is 85% identical to human and bovine RPE65. The RPE65 mRNA was detected in all of the single cone cells isolated from the salamander retina, as well as in the retinal pigment epithelium by RT-PCR, but not in the isolated rods. The RT-PCR products have been confirmed to be RPE65 by DNA sequencing. The results indicate that this potential retinoid processing protein is expressed in the cone photoreceptor cells but not in rods. Therefore, this protein may contribute to the unique retinoid processing capabilities in salamander cones.     

Dicationic furans inhibit development of Cryptosporidium parvum in HSD/ICR suckling Swiss mice

The efficacy of dicationic diarylfurans was evaluated against Cryptosporidium parvum by a suckling murine model. Candidate drugs were solubilized or suspended in deionized water and administered orally at a constant dose rate on days 0-5 (treatment day 0) to suckling ICR Swiss mice experimentally inoculated with oocysts of C. parvum. Efficacy was based on numbers of oocysts recovered from the intestinal tracts of mice subjected to necropsy examination on day 6. Numerous candidate furans significantly reduced the numbers of oocysts recovered from treated mice compared with control mice. Compounds 1, 2, 4, and 9 demonstrated superior efficacies (10% of controls or better) against C. parvum. Compounds 3, 5, 6, 7, 8, 11, 17, 18, and 19 also significantly reduced the numbers of oocysts recovered from treated mice but demonstrated efficacies ranging from 17 to 65% of controls. Compound 4 was particularly efficacious against C. parvum at a dosage as low as 8.5 mg/kg of body weight. Compound 4 is identified as a lead compound for additional studies in other animal models.     

Preoperative biliary drainage, colonisation of bile and postoperative complications in patients with tumours of the pancreatic head: a retrospective analysis of 241 consecutive patients

OBJECTIVE: To analyse the outcome of preoperative biliary drainage in patients being operated on for a tumour in the pancreatic head. DESIGN: Retrospective study. SETTING: University hospital, The Netherlands. SUBJECTS: Consecutive series of 241 patients. MAIN OUTCOME MEASURES: Decline in bilirubin concentrations and bacterial contamination of bile as a result of preoperative drainage. Incidence of postoperative complications in patients who underwent preoperative drainage and those who did not. RESULTS: 184/241 patients underwent preoperative biliary drainage. Endoscopic drainage was the most effective, shown by a median reduction in bilirubin concentrations of 82%, 74%, and 50% after endoscopic drainage (n = 149), papillotomy (n = 25) and external drainage (n = 10), respectively. Bacterial contamination of bile was significantly more common when an endoprosthesis was used, but did not result in a higher rate of infective complications. 163 Whipple's resections, 33 total pancreatectomies, and 45 biliary-enteric bypasses were performed. 137/241 (57%) patients had postoperative complications. There was no significant difference in the incidence of postoperative complications between patients who had preoperative biliary drainage and those who did not (p = 0.4).