1. A technique is described for the removal of subcellular contaminants from intact rat intestinal brush borders, and for the subsequent separation of a microvillus membrane fraction from a fibrillar residue. 2. Increments in invertase activity, microscopic homogeneity and low nucleic acid content indicate that the microvillus plasma membrane has been extensively purified. Multiple membrane preparations have been shown to be highly reproducible with respect to their invertase specific activity, cholesterol content and phospholipid content. Alkaline phosphatase, leucine aminopeptidase, Mg(2+)- and Ca(2+)-dependent adenosine triphosphatase and seven separate disaccharidases were shown to be predominantly confined to the membrane fraction. 3. The fibrillar fraction has been shown to contain approximately 30% of the total protein of purified brush borders, plus most of the residual nucleic acid contaminant. No evidence was found for the localization of any specific enzyme in this fraction.
Previously, we demonstrated that the hydrophobic surfactant Pluronic L-81 (L-81) inhibits the intestinal formation and transport of chylomicrons (CM) but not of very low-density lipoprotein-sized (VLDL) particles. The present study was undertaken to determine whether infusion of egg lecithin results mainly in secretion of VLDL by the small intestine and whether L-81 has any effect on their formation and secretion. Intestinal fistula rats were infused intraduodenally at a rate of 3 ml/h with a lipid emulsion containing 20 mM egg lecithin and 19 mM sodium taurocholate for 8 h. This was then followed by another 8 h of infusion of a similar lipid emulsion but with 0.5 mg/h of L-81 added. Lymphatic lipid output was measured, and lymph lipoproteins were sized by use of electron microscopy. Whether L-81 was present or not, no significant difference was detected in the lymphatic triglyceride, phospholipid, or cholesterol outputs. Based on agarose gel electrophoresis, sizing of intestinal lymph lipoproteins, and also the determination of lipid in the intestinal lymph CM and VLDL as separated by ultracentrifugation, VLDL were the major lipoproteins present in lymph during the infusion of egg lecithin. Thus, intraduodenal infusion of egg lecithin in the rat results mainly in the transport of VLDL and is not affected by the administration of L-81. The results suggest that CM and VLDL are assembled separately by the enterocytes and indicate the usefulness of L-81 in further investigating the pathways and regulation of intestinal lipoprotein synthesis, assembly, and secretion.
Three hundred seventy patients with recently healed duodenal ulcer entered into a one-year, double-blind, randomized multicenter trial comparing placebo with three different dose schedules of cimetidine (200 mg twice a day, 300 mg twice a day, and 400 mg at bedtime) for the prevention of recurrent duodenal ulcer. By the end of one year, the cumulative symptomatic recurrence rate as demonstrated by endoscopy was similar for the patients receiving the three dosages of cimetidine (19 per cent, 15 per cent, and 13 per cent, respectively; not significant), whereas the placebo-treated group had a 34.7 per cent symptomatic recurrence rate (P less than 0.01 as compared with each cimetidine group). Cigarette smoking was found to be an important variable; among the placebo recipients ulcer recurrence was significantly more likely in smokers (72 per cent) than in nonsmokers (21 per cent, P less than 0.001). The frequency of ulcer recurrence in smokers was significantly reduced by treatment with cimetidine (from 72 per cent to 34 per cent, P less than 0.). Smokers who received cimetidine were at least as likely to have a recurrence as were nonsmokers who received placebo (34 per cent vs. 21 per cent, not significant). Thus, smoking appears to be a major factor in recurrence of duodenal ulcer, and in smokers, giving up smoking may be more important in the prevention of ulcer recurrences than administration of cimetidine.
Treatment of rats with puromycin and acetoxycycloheximide results in a defect in intestinal lipid transport. Under these conditions rats given corn oil accumulate triglyceride within the intestinal cells and fail to develop the normal postprandial hyperlipemia. The observed interference in lipid transport appears to be a consequence of impaired chylomicron formation.
SUMMARY
Aim:1To compare the safety and efficacy of pantoprazole and ranitidine in maintaining erosive oesophagitis healing. Methods: Gastro-oesophageal reflux disease patients (349) with endoscopically documented healed erosive oesophagitis (grade 0 or 1) were randomly assigned to receive pantoprazole (10, 20 or 40 mg/q.d.s.) or ranitidine (150 mg/b.d.). Erosive oesophagitis status was assessed endoscopically at months 1, 3, 6 and 12 or when relapse symptoms appeared (relapse ¼ reappearance of erosive oesophagitis grade 2 within 12 months). Symptom-free days were also assessed. Results: Pantoprazole 20-and 40-mg were significantly more effective than ranitidine in maintaining healing regardless of initial erosive oesophagitis grade.Response was dose-related. After 12 months 78, 55, 46 and 21% of patients remained healed (40-, 20-, 10-mg pantoprazole and ranitidine). Pantoprazole 40-mg produced significantly more symptom-free days (83%) than ranitidine (58%). Heartburn-free days/ nights were significantly higher with pantoprazole 40-mg (92 and 93%) than ranitidine (73 and 77%). The most frequent reason for discontinuation, unsatisfactory efficacy, occurred most often with ranitidine (P < 0.001). Conclusion: Once-daily pantoprazole therapy prevented relapse of healed erosive oesophagitis more effectively than ranitidine and with fewer heartburn days. Response to pantoprazole was dose-related. Pantoprazole 40-mg was the most effective regimen and consistent in maintaining erosive oesophagitis healing with a good safety and tolerability profile.
H,-receptor antagonist therapy is associated with a low incidence of adverse reactions. Adverse events reported in clinical trials of ranitidine in daily doses of up to 1200 mg include headache, tiredness and mild gastrointestinal disturbances, but the incidence is similar to or less than that for placebo. High doses of cimetidine ( > 5 g/day) can cause reversible impotence or gynaecomastia. While ranitidine exhibits no clinically significant drug-drug interactions, cimetidine interacts with many drugs metabolized by cytochrome P450. In contrast to ranitidine and cimetidine, where safety data are available for up to 10 years of continuous therapy, experience with famotidine and nizatidine is limited. The safety of long-term H,receptor antagonist therapy needs to be considered in relation to the potential consequences of prolonged acid suppression, including the risk of proliferation of gastric flora and the risk of developing enterochromaffin-like cell hyperplasia, which could in turn, theoretically, lead to gastric malignancy. Such problems have not been observed in patients during long-term therapy at low or full doses of H,-receptor antagonists. Standard doses of currently available H,-receptor antagonists permit acid secretion in response to food and other stimuli, and this daily acid tide prevents persistent bacterial colonization.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.