Absorption of 7-ketolithocholic acid in rat jejunum, ileum and colon

7-Ketolithocholic acid is a bile acid which is formed in the intestine of man by bacterial oxidation of chenodeoxycholic acid and ursodeoxycholic acid. In contrast to deoxycholic acid and lithocholic acid 7-ketolithocholic acid after its intestinal absorption may be reduced in the liver to chenodeoxycholic acid or ursodeoxycholic acid. In the present study absorption of 7-ketolithocholic acid in jejunum, ileum, and colon was measured. When 7-ketolithocholic acid was perfused with a concentration of 0.025 mmol/l the absorption in the jejunum was 6.2 +/- 0.9 nmol/cmxh (mean +/- SD), in the ileum 8.1 +/- 0.2 nmol/cmxh, and in the colon 11.2 +/- 1.7 nmol/cmxh. The absorption of 7-ketolithocholic acid in jejunum, ileum, and colon was equal to the absorption of ursodeoxycholic and chenodeoxycholic acid. The equal absorption rates of 7-ketolithocholic, ursodeoxycholic, and chenodeoxycholic acid indicate, that substitution of the 7-hydroxyl group by the 7-keto group has no influence on the intestinal absorption of bile acids. The excellent colonic absorption of 7-ketolithocholic acid demonstrates, that not only the small intestine but also the colon contributes to the enterohepatic circulation of bile acids.     

Transmural electrical potential difference of the human colon

The electrical potential across the human colon was measured by a technique which accurately reflects the true mucosa-to-serosa potential difference. Large negative mucosal potentials were recorded from all regions. The potential difference of the sigmoid colon was significantly greater than that of the rectum. The technique may have important applications to the further study of normal or abnormal colonic function.     

Tumours of the midgut (jejunum, ileum and ascending colon, including carcinoid syndrome)

(Neuro-)endocrine tumours of the gastrointestinal tract are also called 'carcinoids'. (Neuro-)endocrine midgut tumours can be categorized according to their clinical behaviour. Most tumours are non-functioning. Functioning tumours are responsible for the carcinoid syndrome. The carcinoid syndrome is almost uniquely associated with midgut carcinoids. Symptoms of the carcinoid syndrome are caused by an excess of biogenic amines, peptides and other factors in the circulation. The typical symptoms of the carcinoid syndrome are diarrhoea, flushing, and carcinoid heart disease. Carcinoid heart disease involves the tricuspid and pulmonary valves and the endocardium. Serum chromogranin A and urinary excretion of 5-hydroxy-indoleacetic acid (5-HIAA) are biochemical markers. Carcinoid tumours express large numbers of high-affinity somatostatin receptors. These can bind the currently available octapeptide somatostatin analogues. In inoperable patients, biotherapy with somatostatin analogues and interferon-alpha is the treatment of choice. Somatostatin analogues and interferon-alpha significantly improve symptoms.     

Comparative effects of growth hormone on water and ion transport in rat jejunum,ileum, and colon

Specific growth hormone (GH) receptors are located along the entire rat intestine. We have recently shown that GH induces water and ion absorption in the rat ileum. This raises the possibility that GH regulates water and ion transport throughout the intestine. To test this, we have evaluated the effects of GH administration on jejunal, ileal, and colonic water and ion transport, by thein vivo rat perfused intestine, andin vitro, in corresponding segments of intestine mounted in Ussing chambers.In vivo, GH increased water absorption by 250%, 180%, and 80% over baseline in the jejunum, ileum, and colon, respectively. The effect had similar kinetics in the three intestinal regions.In vitro, serosal GH administration induced a decrease in short-circuit current, consistent with an absorptive effect. The effect showed a proximal to distal decreasing pattern. These findings suggest that GH plays a role in the body fluid homeostatic control, promoting water and ion absorption.This work was supported in part by a grant from the Ministero della Sanità AIDS research project 1995, program 9205-35, and by a grant from CNR, no. 94. 02505 CT04.     

Permeability and selectivity of canine and human jejunum during cholera

Increased permeability of the intestinal mucosa to small molecules and ions has previously been proposed as a mechanism causing the profuse diarrhoea characteristic of Asiatic cholera. A technique for measuring absorption rates of (14)C-urea and (3)H-arabinose has been employed to study jejunal permeability during experimental canine and naturally acquired human cholera. The ratio of the absorption rates of these two solutes of different size is an expression of intestinal membrane selectivity and permits calculation of an equivalent pore radius. No change of membrane selectivity was observed in canine loops after challenge with cholera toxin. During naturally acquired human cholera, jejunal pore size was not significantly different from that measured during convalescence. This method was demonstrated to be sensitive to changes induced by amphotericin B, an antibiotic known to alter membrane permeability and selectivity. These data are inconsistent with the hypothesis of increased intestinal permeability during cholera.     

Absorption of urso- and chenodeoxycholic acid and their taurine and glycine conjugates in rat jejunum, ileum, and colon

Chenodeoxycholic acid (cheno) and ursodeoxycholic acid (urso) dissolve cholesterol gallstones in man. Comparative studies of the absorption of cheno and urso are not available. The absorption of urso and cheno and their glycine and taurine conjugates in jejunum, terminal ileum, and colon of the rat were therefore determined in an open in situ perfusion system. Absorption of unconjugated urso and cheno in jejunum, ileum, and colon was similar. In the jejunum conjugated urso and cheno were absorbed only in minimal amounts. In the ileum glycine-conjugated urso was absorbed to a lower extent than glycine-conjugated cheno (6.5 +/- 0.4 vs. 8.6 +/- 0.6 nmol/cm X h at 25 mumol/l bile acid concentration, p less than 0.05) and taurine-conjugated urso was absorbed less than taurine-conjugated cheno (6.4 +/- 0.5 vs. 8.1 +/- 0.7 nmol/cm X h, p less than 0.05). In the colon glycourso and taurourso were not absorbed, while glycocheno and taurocheno were absorbed in small amounts. The low reabsorption rates of urso conjugates in ileum and colon may contribute to the relatively low urso content in bile during urso treatment.     

Effect of lidamidine on transepithelial potential difference evoked by prostaglandin E2 in human jejunum

The effect of the infusion of lidamidine, an antidiarrheal drug, on the change in transepithelial potential difference (TPD) induced by the infusion of prostaglandin E2 (PGE2) was examined in perfused human jejunum in vivo. The increase in luminal negativity of TPD produced by 3 X 10(-7) M PGE2 was significantly decreased from 2.8 +/- 0.5 mV to 1.2 +/- 0.5 mV by the superimposed infusion of 2 X 10(-3) M lidamidine. This result may suggest that lidamidine has an inhibitory effect on intestinal Cl secretion which is stimulated by PGE2.     

Risk of proximal colon neoplasia with distal hyperplastic polyps: a meta-analysis

BACKGROUND: Most guidelines for colorectal cancer screening do not consider distal hyperplastic polyps (HPs) to be markers for proximal colon neoplasia. However, many studies have shown an increased risk of proximal neoplasia (PN) in patients with distal HPs. We performed a systematic review to assess the association between distal HPs and PN. METHODS: We identified studies that compared the prevalence of PN and proximal advanced neoplasia in patients with distal HPs vs controls. Two masked investigators extracted data on individuals with distal HPs, distal adenomas, or no distal polyps. Using the DerSimonian and Laird method, we calculated summary risk ratios. Extensive subgroup analysis was performed. RESULTS: The prevalence of PN and proximal advanced neoplasia in persons with distal HPs was 26.0% and 4.4%, respectively. In studies comparing the risk of PN in patients with distal HPs vs those with no distal polyps, the summary risk ratio was 1.81 (95% confidence interval, 1.20-2.73). However, this increased risk disappeared if only high-quality studies on screening patients were considered. The risk ratio was 0.69 (95% confidence interval, 0.60-0.80) when comparing the risk of PN in those with distal HPs vs those with distal adenomas. CONCLUSIONS: Overall, patients with distal HPs have an intermediate risk of PN compared with those with distal adenomas or no distal polyps; however, in asymptomatic screening individuals, there is no increased risk of PN or proximal advanced neoplasia. The discovery of HPs on screening flexible sigmoidoscopy should not automatically prompt follow-up colonoscopy.     

Identification of insulin receptors in epithelial cells from duodenum, jejunum, ileum, caecum, colon and rectum in the rat

Specific insulin binding was demonstrated in isolated epithelial cells of rat intestine, from the duodenum to the rectum. In every segment tested, insulin binding exhibited similar properties relating to kinetics and specificity and could be interpreted in terms of two populations of receptors possessing different affinities and binding capacities. Insulin receptors were unequally distributed along the intestinal tract, suggesting that the hormone may have varying importance at different points along the intestinal axis. These observations together with previous data on insulin regulation of a number of intestinal epithelial activities suggest that the pancreatic hormone may play an important role in gut physiology from the duodenum to the rectum.     

Discrepancy between effects of cholera toxin on net fluid movement and cAMP levels in rat jejunum,ileum, and colon

Regional differences in the response to cholera toxin were evaluated in rat jejunum, ileum, and colon in vivo.Ligated intestinal loops were exposed to a supramaximal concentration of cholera toxin for 5 hr, and net fluid transport, adenosine 3,5-monophosphate (cAMP) concentrations, and adenylate cyclase and phosphodiesterase activities of mucosal homogenates were determined. The fluid transport response and the specific activities of adenylate cyclase (with and without cholera toxin) and phosphodiesterase declined progressively from the jejunum to the colon. In contrast, cAMP concentrations (with and without cholera toxin) were lowest in the jejunum and highest in the colon. These results demonstrate that cAMP concentrations of the total mucosal homogenate do not parallel cholera toxin-induced fluid secretion in the three intestinal segments. Rather, the activities of adenylate cyclase and phosphodiesterase suggest a relation between fluid secretion and the turnover of cAMP.Supported by Deutsche Forschungsgemeinschaft Grant Lo 114/12-6.     

A study of malabsorption after resection of the entire jejunum and the proximal half of the ileum

Biochemical, haematological, and radiological investigations are reported in a young child in whom nearly 80% of the small intestine was resected. The prognosis in a child after such extensive resection is probably better than in an adult, as natural growth can still occur with the expectation of greater adaptability as well as of increased length of the remaining segments.     

Functional differentiation of human jejunum and ileum: A comparison of the handling of glucose, peptides, and amino acids

The characteristics of glucose, glycine, L-alanine, and glycyl-L-alanine absorption from the jejunum and ileum have been compared in normal human subjects. A perfusion technique has been used, and correct positioning of the perfusion tube has been confirmed by measuring the differential jejunal and ileal handling of bicarbonate.

Glucose and glycine were absorbed faster from the jejunum than from the ileum of all subjects studied, and L-alanine was absorbed faster from the jejunum than from the ileum in five out of six subjects studied. In contrast, the dipeptide glycyl-L-alanine was absorbed at comparable rates from the jejunum and ileum. Higher concentrations of free amino acids were detected in the luminal contents aspirated during the ileal dipeptide perfusions.

These results emphasize the importance of oligopeptide transport in the absorption of protein digestion products, especially in the human ileum, and the practical implications of these findings are discussed.

     

Differential effect of streptozotocin-induced diabetes on the innervation of the ileum and distal colon

The effect of short-term and long-term streptozotocin-induced diabetes on the pattern of distribution and tissue content of adrenergic and peptidergic nerves in ileum and distal (descending) colon of the rat was examined using immunohistochemical, biochemical, and immunochemical techniques. The effect of short-term streptozotocin-induced diabetes on the level of noradrenaline compared with weight-restricted (starved) and untreated controls in the celiac (celiac-superior mesenteric ganglia complex) and inferior mesenteric ganglia, which supply the two regions of the intestine, was also compared. The pattern of change in the distribution of dopamine-beta-hydroxylase-, substance P-, calcitonin gene-related peptide-, and vasoactive intestinal polypeptide-like immunoreactive nerve fibres that was observed in the ileum from diabetic rats was not evident in the myenteric plexus of distal colon. In contrast to the ileum, there was no evidence of degenerative change in any of the nerve types investigated in the myenteric plexus of the distal colon. The level of vasoactive intestinal polypeptide in the diabetic rat ileum was significantly increased, whereas the level of noradrenaline was reduced; no such changes were observed in the distal colon. The tissue content of noradrenaline in the celiac ganglion, which projects to the ileum, was increased at 8-week diabetes compared with both weight-restricted and untreated controls, whereas the diabetic state had no effect on the levels of noradrenaline of the inferior mesenteric ganglion, which projects to the distal colon. It is concluded that there is a differential effect of streptozotocin-diabetes on different regions of the rat intestine. The adrenergic and peptidergic innervation of the distal colon were changed little compared with ileum. This may be explainable in terms of the different functional roles of these two regions of the intestine and/or by the difference in origin of the sympathetic nerves supplying the two regions of the intestine.     

Absorption of nicotine by the human stomach and its effect on gastric ion fluxes and potential difference

We studied gastric absorption of nicotine and the effect of oral nicotine, intravenous nicotine, and cigarette smoking on ion fluxes and potential difference in the human stomach. Nicotine was well absorbed, mean 18.6±3.4% in 15 min, on intragastric instillation at pH 9.8. Absorption was accompanied by side effects of nausea and vomiting, and delay in gastric emptying. Gastric absorption of nicotine at pH 7.4 was less marked (mean 8.2±2.9%), but was negligible at pH 1 (mean 3.3±1.4%). Intragastric nicotine at pH 7.4 and 9.8 stimulated gastric acid output either during instillation (pH 9.8) or during subsequent acid instillation (pH 7.4). Rapid cigarette smoking and intravenous nicotine suppressed gastric acid output. Neither oral administration nor intravenous infusion of 4 mg nicotine base per hour nor smoking 3–5 cigarettes per hour significantly altered the gastric mucosal barrier as measured by gastric ionic fluxes and potential difference. In conclustion, (1) the base nicotine (pK8.5) is well absorbed from the human stomach at pH 9.8, but poorly absorbed at pH 1.0; (2) gastric absorption of nicotine delays gastric emptying; (3) intragastric nicotine at and above neutral pH appears to have a mild stimulating effect on gastric acid output, while rapid cigarette smoking or intravenous infusion of nicotine suppresses acid output; (4) nicotine does not alter the gastric mucosal barrier to sodium ion movement nor affect potential difference.This work was supported in part by grants from the Australian Tobacco Research Foundation, the National Health and Medical Research Council of Australia, and the Medical Research Service of the Veterans Administration. The technical assistance of Mr. P. Settree, BSc, is gratefully acknowledged.     

Ontogeny of procholecystokinin maturation in rat duodenum, jejunum, and ileum.

Expression and processing of procholecystokinin (proCCK) in rat intestine during development were examined using sequence-specific immunoassays, cleavage with processing-like enzymes, and chromatography. Fetal proCCK concentrations were similar in duodenum, jejunum, and ileum, but the maturation to CCK followed different courses: duodenal CCK increased from 14 pmol/g in the fetus to 86 pmol/g 4 days after birth and then declined to 17 pmol/g in the adult. In jejunum, CCK varied from 34 pmol/g in the fetus to 127 pmol/g at day 7, decreased to 54 pmol/g at day 21, and increased again to 93 pmol/g in the adult. Ileal CCK decreased from 20 pmol/g in the fetus to 10 pmol/g postnatally. Whereas duodenal proCCK after birth matured completely to carboxyamidated CCK, jejunoileal proCCK matured only partially. Chromatography showed an increase of tyrosine-sulfation and proteolytic processing of N-terminal sequences. At day 7 jejunal cholecystokinin octapeptide (CCK-8) constituted only a minute fraction of the carboxyamidated CCK, of which less than half was sulfated. However, in the adult jejunum, CCK-8 constituted a significant fraction, which was completely sulfated. It is concluded that the CCK gene is well expressed at propeptide level in the fetal small intestine. Postpartum maturation of proCCK, however, is late and differs in the three parts of the small intestine. The belated maturation supports the hypothesis that factors other than CCK regulate pancreatic growth in fetal and neonatal life.