Comparative effects of three resistant starch preparations on transit time and short-chain fatty acid production in rats.

A high-fiber diet may protect against colon cancer because of the butyrate generated in the colon by bacterial fermentation of nonstarch polysaccharides. Butryrate can reverse neoplastic changes, at least in vitro, and resistant starch (RS) represents a source of butyrate in vivo. We examined the effects of replacing normal maize starch in the diet of rats with three preparations of RS on the amounts of starch, butyrate, and other short-chain fatty acids in the cecum. We examined the effects on fecal bulking and transit time, which have been suggested to protect against colon cancer. The RS preparations that we tested were potato starch, high-amylose maize starch, and an alpha-amylase-treated high-amylose maize starch. All had major effects on fecal weight and on the weight of the cecum but only slightly shortened transit times. All increased the amount of starch reaching the cecum and increased short-chain fatty acid production in the cecum; potato starch had the greatest effect and high-amylose maize starch the least. Potato starch, unlike high-amylose maize starch, enhanced the proportion of butyrate. Thus there were marked differences among sources of RS, even though these were all classified as RS2. The significance for colon cancer is discussed.

Aspirin changes the secretion rate and amino acid composition of human small intestinal mucin in subjects with ileal conduits.

The effect of aspirin on the rate of secretion and amino acid composition of human ileal mucin was studied, using subjects with ileal conduits as a model system in which mucin secreted from the ileal conduit tissue is flushed out in the urine and can be measured and analysed. Aspirin (600 mg per day, administered orally) increased the daily mucin output by 37-104% in subjects by days 3 or 4, but thereafter the mucin output declined to below the baseline level by day 10. Mucin samples, purified from the ileal conduit urine during the control period and during aspirin administration, were compared. There were no discernible changes in the degree of polymerisation or the density, but during aspirin administration the amino acid composition was significantly changed, and in particular threonine and proline were enriched. One possible explanation, consistent with the compositional analyses, is that the N- and C-terminal regions of the mucin subunits have been cleaved off and lost during aspirin administration. The observed changes in mucin secretion may have implications for the mechanism of the toxic effects of aspirin on the small intestine by altering the barrier properties of the mucus layer.

A constituent of human small intestinal mucus that copurifies with mucin and can interfere with raising antibodies to the mucin.

The accuracy of an immunoassay for mucin depends on the antibodies' specificity. During human small intestinal mucin purification on a CsCl gradient, a very antigenic non-mucin contaminant was found at 1.48 g.ml-1 density. This was separated from the mucin (1.42 g.ml-1 density) by dividing the gradient into 26 fractions, but not by dividing it into 8 fractions. Polyclonal antibodies raised against mucin obtained using 8 fractions reacted with mucin and contaminant, but antibodies raised against mucin obtained using 26 fractions reacted only with mucin. The identity of the contaminant is unknown. However, it contained nearly equal amounts of galactose, N-acetylglucosamine and glucose, but did not react strongly with periodate-Schiff reagent. Immunofluorescence microscopy showed it was located in the small intestinal goblet cells and mucus layer. Unless the contaminant is removed before raising polyclonal antibodies to mucin, immunoassays will give inaccurate results.

Comparison of the ileal and faecal digestibility of dietary amino acids in adult humans and evaluation of the pig as a model animal for digestion studies in man.

The aim of the study was to determine if there is a difference between ileal and faecal assays for determining amino acid and N digestibilities in adult human subjects. Comparison of true ileal amino acid and N digestibilities was also made between adult human subjects and growing pigs to establish the usefulness of the pig as a model animal. Five subjects with established ileostomies and six subjects with intact large bowels consumed a constant diet consisting of meat, vegetables, fruit, bread and dairy products for 7 d with collection of ileostomy contents or faeces respectively over the last 4 d. The study was repeated using 25 kg body weight ileostomized and intact pigs. Apparent amino acid and N digestibility coefficients were determined. For human subjects the faecal digestibility values were significantly higher (P < 0.05) than the ileal values for Arg, Asp, Gly, Phe, Pro, Ser, Thr and Trp. The faecal digestibility of Met was significantly lower than the ileal value. Determination of DNA, diaminopimelic acid (DAPA) and the digestibilities of pectin, hemicellulose and cellulose in human subjects indicated that some microbial colonization had occurred at the terminal ileum after formation of an ileostomy; however, this was not as extensive as in the large intestine. True ileum amino acid and N digestibilities were calculated after correcting for the endogenous contribution of amino acids at the terminal ileum determined using a protein-free diet. There were no significant differences between adult human subjects and pigs for true ileal dietary amino acid digestibility except for Thr, Phe, Cys and Met. There were no significant differences between adult humans and pigs for the ileal digestibility of dry matter and the faecal digestibility of gross energy.

Effect of Helicobacter pylori infection on colloidal bismuth subcitrate concentration in gastric mucus.

Necropsy gastric mucus infected with Helicobacter pylori has a reduced capacity to concentrate colloidal bismuth subcitrate when compared with non-infected mucus. Mucus mounted in a modified in vitro diffusion chamber was bathed with colloidal bismuth subcitrate solutions at different concentrations and pH levels. Bismuth was measured by atomic absorption spectrophotometry to assess intramucus colloidal bismuth subcitrate concentrations. Bismuth concentrations in non-infected mucus were higher than in Helicobacter pylori infected mucus at all experimental colloidal bismuth subcitrate concentrations and pH levels. Regardless of the infection status, the intramucus concentration of colloidal bismuth subcitrate was dependent upon the concentration of the bathing solution and independent of the pH and the mucus thickness. Colloidal bismuth subcitrate solubility in saline solution varied with pH, and was least soluble in the pH range 1.1 to 3.25 and more soluble above and below this pH range. This study suggests that Helicobacter pylori infection is associated with physicochemical changes in the gastric mucus with a reduction in its capacity to concentrate colloidal bismuth subcitrate. Such a reduction may compromise the attainment of optimum colloidal bismuth subcitrate concentrations necessary for its bactericidal activity.

The clinical associations with hepatic steatosis: a retrospective study.

Hepatic steatosis is a common liver biopsy finding. As a preamble to a study of nonA, nonB hepatitis we aimed to determine the clinical associations in patients who had hepatic steatosis on biopsy. All liver biopsies performed in the gastroenterology department at Auckland Hospital between 1986 and 1989 were reviewed for evidence of steatosis and the clinical associations analysed. Steatosis was present in 69 (43.7%) of 158 liver biopsy specimens with 35 being mild (47%), 29 moderate (45%) and five severe (7%). Excess alcohol intake was the probable aetiological association in 28 (45%), obesity in 17 (27%) and diabetes mellitus in seven (11%). No causal association could be identified in 17 (24%) and included three of the five cases with severe steatosis. There were no significant differences in clinical presentation, biochemistry or hepatic histopathology between alcoholic and nonalcoholic steatosis. Nonalcoholic steatosis appeared to be more benign with only one case of cirrhosis but further follow up is required to determine true prognosis.

The ion exchange properties of human post-mortem caecal and colonic mucus: the effect of sodium butyrate.

This study examined Na+/H+ ion exchange of caecal and colonic mucus. Two distinct Na+/H+ ion exchange populations of caecal mucus were identified, one group being a cation exchanger and the other an anion exchanger, suggesting that caecal mucus has ampholyte properties responsive to changing physical and chemical properties of luminal contents. Mucus from the colon was consistently an anionic exchanger--this may aid water and electrolyte absorption in the colon. When mucus was incubated with sodium butyrate, the Na+/H+ ion exchange properties of the mucus were decreased.

Use of the ileal conduit as a model for studying human small intestinal mucus glycoprotein secretion.

To establish a human model system for investigating control of mucus secretion by the small intestine, we have studied the output of mucus glycoprotein in the urine of patients with ileal conduits. A highly specific enzyme-linked immunosorbent assay (ELISA) was used to measure mucus glycoprotein with a sensitivity down to 0.3 ng protein of mucus glycoprotein. The assay detects human ileal mucus glycoprotein in the urine of ileal conduit patients; for an individual subject, the amount hardly varied from day to day, although there were substantial differences between individuals in the amounts secreted. Control urine from persons with normal bladders did not contain any mucus glycoprotein that reacted in the ELISA. The model has many advantages over other experimental systems for studying the rate of mucus glycoprotein secretion from the human ileum and can also be used as a reproducible resource of undegraded mucus glycoprotein.

Bile acids of marsupials. 2. Hepatic formation of vulpecholic acid (1 alpha,3 alpha,7 alpha-trihydroxy-5 beta-cholan-24-oic acid) from chenodeoxycholic acid in a marsupial, Trichosurus vulpecula (Lesson).

Free vulpecholic acid (1 alpha,3 alpha,7 alpha-trihydroxy-5 beta-cholan-24-oic) is the major biliary component of the Australian opossum (Trichosurus vulpecula), accompanied only by a few percent of its taurine conjugate. In order to exclude a microbial involvement in its formation (i.e., secondary origin) four sets of experiments were performed. It was found that a) the level of vulpecholic acid remained unchanged in the bile of opossums fed with neomycin and kanamycin for 7 days prior to bile collection; b) it also remained unchanged after long bile drainage; c) in opossums prepared with biliary cannula, intraportally injected [24-14C]chenodeoxycholic acid was transformed to [24-14C]vulpecholic acid; and d) in a similar experiment, the detectable transformation of [1 alpha,2 alpha-3H2]cholesterol to vulpecholic acid was observed. In experiment c) 28-66% of the administered radioactivity was secreted in 2 h in the form of free biliary vulpecholic and chenodeoxycholic acids. Only a trace amount of the corresponding taurine conjugates (approximately 0.4%) was formed. Moreover, rapidly declining specific radioactivity of the unconjugated chenodeoxycholic acid indicated its probable participation in the native formation of vulpecholic acid.

Relation of Helicobacter pylori to the human gastric mucosa in chronic gastritis of the antrum.

The spatial relations between bacteria and the affected tissues can indicate pathogenic mechanisms. This study was undertaken to define the spatial relation of Helicobacter pylori to the human gastric mucosa. Antibodies against gastric mucus and ruthenium red were used to stabilise the glycoprotein structure of the mucus and glycocalyces in antral biopsy specimens from eight patients infected with H pylori. The location of organisms and ultrastructural features were assessed using systematic scanning and transmission electron microscopy: 92 (2)% (mean (SE] of H pylori were in the pit mucus, and 7 (3)% were in the surface mucus; 60 (12)% of H pylori were close to epithelial cells, with only 5 (2)% located near the epithelial intercellular junctions. Fine filamentous strands extended between organisms and nearby epithelial cells, with few organisms in membrane to membrane contact. H pylori were not observed between, beneath, or within cells of the gastric mucosa. The preferred location of H pylori in the gastric antrum is within the pit mucus close to the epithelial cell surface, with no evidence that they have a direct toxic effect on the mucosa.

The Na+/H+ exchange and H+ diffusion properties of human postmortem mucus: a comparison of gastric antral, gastric body, jejunal and ileal mucus.

The stomach and small intestine are areas of major electrolyte and solute transport. Mechanisms of transport in these areas have been widely studied and basic understanding is available. However, the mucus that lines the stomach and intestine is an important layer whose properties and functions in electrolyte and solute transport are not well understood. In this study we examined the Na+/H+ exchange of mucus from the stomach body and antrum, the jejunum, and the ileum. Mucus from the stomach body and antrum is a cation exchanger, a property that aids the net unidirectional flux of H+ ions from parietal cells to lumen. In the jejunum and ileum, mucus is an anion exchanger, which may be important in solute transport and absorption in the small bowel. In both the stomach and small bowel, proton movement is slow, which helps maintain the uphill pH gradient across gastric mucus and the downhill pH gradient across small intestinal mucus.

Acute lithium toxicity--chorea, hypercalcemia and hyperamylasemia.

Lithium is widely used in the management of patients with manic depressive illnesses. It is a valuable drug with a good safety record but occasionally causes severe disorders. A 71-year-old woman is described who previously had a good response to lithium carbonate treatment of a manic depressive illness. Because the patient appeared depressed and withdrawn, lithium carbonate dosage was increased. The development of confusion and choreiform movements precipitated hospital admission. The symptoms were relieved when lithium was stopped but recurred with the reinstitution of lithium. Spontaneous choreiform movements were again relieved on lithium withdrawal. Associated with the abnormal movements were alterations in the serum calcium concentrations, a rise in the parathyroid hormone concentration and a rise in the serum amylase concentration without features of acute pancreatitis.

Na+/H+ ion-exchange property of postmortem human gastric mucus. The effects of Campylobacter pylori infection and sucralfate.

The effect of Campylobacter pylori infection and sucralfate treatment on the ion-exchange property of human gastric mucus from 17 human postmortem stomachs was investigated in an in vitro chamber. Of the 10 stomachs not infected with C. pylori mucus from 4 stomachs had a 'normal' Na+/H+ exchange capacity, whereas 6 were without a Na+/H+ exchange capacity. The Na+/H+ exchange capacity of the seven stomachs infected with C. pylori was half that of the four 'normal' uninfected stomachs. Sucralfate significantly improved the Na+/H+ exchange capacity of mucus from C. pylori-infected stomachs and from the uninfected stomachs without Na+/H+ exchange. This study shows that impairment of the Na+/H+ exchange capacity of gastric mucus is associated with C. pylori infection and that sucralfate improves the Na+/H+ exchange capacity of gastric mucus.

Ammonia produced by Campylobacter pylori neutralizes H+ moving through gastric mucus.

We aimed to show that Campylobacter pylori infection increases the concentration of ammonia in the gastric mucus and alters the movement of H+ through the mucus. Mucus from uninfected and C. pylori-infected stomachs was collected at postmortem. Ammonia was measured enzymatically. The ammonia concentration in C. pylori-infected mucus was fourfold greater than in uninfected mucus. H+ movement experiments were carried out using an in vitro chamber, in which a layer of mucus separated a 0.1 M HCl solution from distilled H2O. The change in pH of the distilled H2O was measured over 30 min. A drop in pH was measured for uninfected mucus. A slight rise in pH was measured for C. pylori-infected mucus. We conclude that C. pylori infection is associated with reduced H+ movement through mucus and that this may be due to increased ammonia concentration within mucus.

Sucralfate interactions with gastric mucus.

Sucralfate protects the stomach against a number of experimental damaging agents and is efficacious in the treatment of peptic ulcer disease. It binds with acidity to the base of an ulcer to form a protective barrier. Sucralfate also enhances prostaglandin synthesis and release in the mucosa. In this study, the rat stomach was examined to determine sucralfate's interaction with gastric mucus. Mucus in the rat stomach forms a distinct and continuous blanket. In snap-frozen samples, pretreatment with phosphate-buffered saline as a control shows a layer of mucus of homogeneous structure thinner than the homogeneous layer after pretreatment with antibodies developed against rat gastric mucus. Pretreatment with the surface protective agent sucralfate shows some increase in the thickness of mucus with a thin dense sublayer adjacent to the epithelium and a less dense-appearing outer zone of variable thickness. Analysis of x-rays generated by the electron beam on windows of mucus and epithelium showed the expected gradients of sodium, potassium, chloride, and sulfur. The percentage of aluminum and sulfur in the mucus was higher in sucralfate-treated samples than in controls. Interaction between sucralfate and gastric mucus needs further investigation.

Na+/H+ ion-exchange property of postmortem human gastric mucus.

The Na+/H+ ion-exchange property of human gastric mucus and its relationship to age has been studied. Mucus was collected from 40 postmortem human stomachs (age range, 21-83 years) within 24 h of traumatic death. Twenty-one stomachs (age range, 21-76 years) were free of Campylobacter pylori infection and histologic gastritis. Mucus from these stomachs was consistently a cation exchanger at pH 6 in an in vitro system. The cation-exchange capacity of mucus from seven stomachs within the age range 55-70 years was 50% less than the cation-exchange capacity of mucus from eight stomachs within the age range 20-35 years. This study shows that human gastric mucus at pH 6 is a cation exchanger and that the ion-exchange capacity decreases with age.