Update on Helicobacter pylori research. Dyspepsia.
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Anti-Inflammatory Agents, Non-Steroidal↗
Biomedical subjects
E Roda
Publications and source records attributed to E Roda.
Species differences in hepatic bile acid uptake: comparative evaluation of taurocholate and tauroursodeoxycholate extraction in rat and rabbit.
Dose-response curves for taurocholate and tauroursodeoxycholate were performed in rat and rabbit livers to get more insight into species differences in the hepatic bile acid uptake. The bile acids showed saturation kinetics in both animals, the Vmax in rat being higher than in rabbit and the Km being lower in the rat than in the rabbit for both the bile acids, with no significant difference in the hepatic cells morphometric parameters. Therefore, it is possible that differences in the kinetic parameters are related to the number and, to a lesser extent, to the affinity of the transporters on the sinusoidal plasma membranes.
Animals↗
Relationship between structure and intestinal absorption of bile acids with a steroid or side-chain modification.
UNLABELLED: A structure-activity relationship for bile acid (BA) intestinal absorption is known to exist. To better understand the BA structural requirements for optimal BA intestinal absorption, rabbit ileal perfusion studies were performed. Unconjugated BA: Ursodeoxycholic (UDCA) and ursocholic acid (UCA) with methyl (6MUDCA and 6MUCA) or fluoro group (6FUDCA and 6FUCA) in the 6 position and UCA with a methyl group in 23 position (23MUCA) were compared with unconjugated UDCA, UCA, deoxycholic (DCA), chenodeoxycholic (CDCA), hyocholic (HCA), and hyodeoxycholic (HDCA) acid. BA lipophilicity was evaluated by their octanol-water partition coefficient. Conjugated BA: Taurine-conjugated UDCA and UCA with a methyl group in the 23 position (T23MUDCA and T23MUCA) were compared with the corresponding taurine-conjugated natural analogs. An analog of glycine-conjugated UDCA with the C24 amide bond replaced by a -CO-CH2- in the 24 position (24PUDCA) was studied and results were compared with the natural form (GUDCA). Unconjugated BA absorption was dose dependent (i.e., passive) and followed their lipophilicity: DCA > 6MUDCA > CDCA > HDCA > UDCA > HCA > 6FUDCA > 6MUCA > 6FUCA > UCA. Conjugated BA absorption was active, and Vmax was in the following order: TCA > TUDCA > TUCA > T23MUCA > T23MUDCA > 24PUDCA > GUDCA. 24PUDCA transport was also active and higher than GUDCA. CONCLUSION: Passive transport is dependent on BA lipophilicity. Conjugated BAs are actively transported, and the presence of a 23-C methyl group does not improve transport when compared with the natural analogs. The substitution of the C24 amide bond with a -CO-CH2-still affords interaction of the BA with the intestinal transport carrier.
Animals↗
Alpha interferon treatment may prevent hepatocellular carcinoma in HCV-related liver cirrhosis.
BACKGROUND/AIMS: The aims of alpha-interferon treatment for chronic viral liver infections are clearance of the virus and healing of the disease. Hepatocellular carcinoma is a complication of viral cirrhosis; but it is not yet known whether treatment of viral cirrhosis with alpha-interferon prevents this complication. METHODS: The incidence and the risk (Cox regression analysis) of developing hepatocellular carcinoma were calculated in 347 patients with hepatic cirrhosis; 227 (34 hepatitis B virus and 193 hepatitis C virus related) were treated with alpha-interferon and 120 (28 hepatitis B virus and 92 hepatitis C virus) did not receive this treatment, in order to evaluate the efficacy of alpha-interferon in the prevention of hepatocellular carcinoma. In all patients, the cirrhosis was well compensated (Child A). RESULTS: Over mean follow-up periods of 49 months for hepatitis B virus and 32 months for hepatitis C virus, 20/347 patients (6/62 hepatitis B virus and 14/285 hepatitis C virus) developed hepatocellular carcinoma. The risk of developing this tumor was significantly greater in males (p < 0.007) and in patients not treated with alpha-interferon (p < 0.01). The Relative Risk of developing hepatocellular carcinoma increased significantly (p < 0.0002) with each passing year. In patients with hepatic cirrhosis secondary to hepatitis B virus infections, the risk did not seem to be modified by alpha-interferon treatment, even though a greater, but not significant risk (Relative Risk = 4.9; p = 0.3) was calculated for untreated patients; in contrast, in hepatitis C virus-related cirrhosis, this risk was reduced by a factor of 4.0 (p = 0.04). The tumor developed only in non-responder patients regardless of virus type. After adjustment for confounding factors (sex, age, alcohol consumption, cigarette smoking), a statistically significant (p < 0.025) effect of interferon treatment in preventing hepatocellular carcinoma was still demonstrated when responders were matched with controls, but not when responders were compared with non-responders. CONCLUSIONS: These results show that, in addition to its ability to halt the progression of viral-induced liver disease, alpha-interferon is also of benefit in patients with hepatitis C virus cirrhosis who respond to this treatment by lowering their risk of developing hepatocellular carcinoma.
Adolescent↗
Intestinal absorption of bile acids in the rabbit: different transport rates in jejunum and ileum.
BACKGROUND & AIMS: A direct comparison of jejunal and ileal absorption rates of bile acids has not been reported. The aim of this study was to compare the relative transport rates of different bile acids in the jejunum and ileum. METHODS: Jejunal and ileal rabbit intestinal segments were separately perfused with bile acid solutions, and dose-response curves were obtained for taurocholate, ursodeoxycholate, chenodeoxycholate, deoxycholate, and their glycoconjugates. Membrane fluidity and bile acid transport were assessed in brush border membrane vesicles. RESULTS: Taurocholate showed active transport in the ileum and no transport in the jejunum. Unconjugated bile acids showed passive diffusion in the two tracts, whereas glycoconjugated bile acids showed both components of transport in the ileum and passive diffusion in the jejunum (lower in the latter). A higher membrane fluidity and lower cholesterol-to-phospholipid ratio were found in the jejunum. Ursodeoxycholate reduced bile acid uptake into membrane vesicles from both ileum and jejunum. CONCLUSIONS: Active transport is limited to the ileum. Passive diffusion is higher through a less fluid membrane with a higher cholesterol-to-phospholipid ratio in the ileum than in the jejunum. Ursodeoxycholate inhibition may be at the level of a facilitated, sodium-independent diffusion in the jejunum.
Animals↗
[Intrahepatic cholestasis in chronic liver disease].
Cholestasis syndromes are characterized by a reflux of compounds usually excreted with bile. ATP dependent carriers and cytoskeleton proteins guarantee physiological bile flux. There are several clinical conditions in which this system is affected. Intrahepatic cholestasis is characterized by damage to hepatocytes or intrahepatic bile ducts. Primary biliary cirrhosis and primary sclerosing cholangitis represent examples of cholestatic chronic liver disease. The pathogenesis of these two conditions seems to be mediated by immunological reactions. Moreover, hepatitis viruses are able to induce cholestasis.
Cholestasis, Intrahepatic↗
Epidemiology of gallstone disease in Italy: prevalence data of the Multicenter Italian Study on Cholelithiasis (M.I.COL.)
This study was designed to obtain a general overview of gallstone disease in Italy. A total of 18 cohorts in 10 Italian regions were enrolled in this survey. Four cohorts were excluded from analysis because of a participation rate of less than 50 percent. Field activities started in December 1984 and terminated in April 1987. A precoded questionnaire was administered to each subject by a trained member of the medical staff. Participants underwent an ultrasonographic examination of the upper abdomen and blood sampling. Each research group was provided with an identical ultrasonographic machine. Standardized criteria were established for both the examination and diagnosis. The inter- and intraobserver variation in the ultrasonographic procedure was assessed using a reliability study. The overall kappa score for interobserver agreement was good (0.649), while intraobserver agreement was good or excellent (kappa scores > 0.60) in 75 percent of the observers. A total of 29,739 of the 46,139 (64.4 percent) enrolled subjects were examined. Among those with a clear-cut definition of the gallbladder status, 6.5 percent of the males and 10.5 percent of the females had gallstones. Additional 3.0 and 8.4 percents, respectively, had already undergone cholecystectomy. Prevalence of gallstone disease (gallstones plus cholecystectomy) increased linearly with age in both sexes. Among subjects with gallstones, 76.7 percent of men and 72 percent of women were not aware of having gallstones; 87.0 percent of men and 84.9 percent of women were asymptomatic. This study confirms that gallstone disease is a highly prevalent condition. Gallstones rarely cause symptoms, and subjects are mostly unaware of their presence.
Adult↗
The risk of adenomatous polyps in asymptomatic first-degree relatives of persons with colon cancer.
BACKGROUND & AIMS: Increasing evidence indicates that inherited susceptibility is important in the pathogenesis of colorectal neoplasia. The aim of this study was to clarify whether having only one first-degree relative with colorectal cancer increases the risk of developing adenomatous polyps and whether total colonoscopy is an appropriate screening measure in these patients. METHODS: The frequency of such a history was evaluated in 397 asymptomatic patients who underwent total colonoscopy. Of these patients, 155 had colorectal polyps and the remaining 242 did not have polyps. RESULTS: Among polyp cases, 27 of 155 (17.4%) had a positive history; among those without polyps, 12 of 242 (5.0%) had a positive history. Alternatively expressed, 27 of 39 patients (69%) with family history and 128 of 358 patients (36%) without family history had adenomas. The estimated risk for polyps associated with family history was 1.9. Among polyp cases, 14 of 27 patients (51.9%) with family history and 32 of 128 patients (25.0%) without family history had only proximal polyps (chi 2 test; P = 0.006; odds ratio, 3.2), In the same groups, frequency of high-grade dysplasia was 8 of 27 patients (29.6%) and 16 of 128 patients (12.5%), respectively (chi 2 test; P = 0.04; odds ratio, 2.9). CONCLUSIONS: Relative to subjects with no family history, asymptomatic patients with one first-degree relative with colorectal cancer had nearly double the risk of developing adenomatous polyps, greater frequency of severely dysplastic lesions, and significantly higher frequency of proximal polyp location. This suggests that total colonoscopy screening is indicated in these subjects.
Adenomatous Polyposis Coli↗
Bioavailability study of a new, sinking, enteric-coated ursodeoxycholic acid formulation.
A new enteric-coated ursodeoxycholic acid (UDCA) formulation which sinks in the stomach and releases the drug only at a pH > or = 6.5 was developed. In 12 healthy subjects we measured, using a specific enzyme immunoassay, the serum levels of UDCA after a single oral dose of 450 mg of UDCA in three different formulations; enteric coated sinking tablet, stomach-floating enteric coated hard gelatin capsule and conventional gelatin capsule. The drug was given after a meal. Results are expressed as mean +/- SD. The area under the curve [AUC, mumol l-1 (8 h)] following oral administration of enteric-coated, sinking UDCA (39.0 +/- 8.5) was significantly higher than that obtained after both conventional UDCA (30.5 +/- 4.9) and floating enteric coated UDCA (29.3 +/- 3.4). Moreover, the maximum UDCA serum concentration (Cmax) was significantly higher with the enteric coated sinking UDCA formulation when compared to the other two formulations, while the time of maximum UDCA serum concentration (tmax) occurred later. These results may be explained by the hypothesis that the sinking tablet is expelled in the latter phase of gastric emptying along with the solid content. It therefore reaches the intestine at the highest alkalization phase caused by sustained biliary and pancreatic secretions. When released, the protonated insoluble UDCA is promptly solubilized by the alkaline pH thus giving a higher UDCA concentration gradient which facilitates its passive absorption. On the other hand, the floating capsule reaches the intestine too early, still in presence of an acidic pH; and in this condition UDCA is almost insoluble and consequently may be malabsorbed.(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Oral↗
Bile acid structure and intestinal absorption in the animal model.
A close structure-activity relationship exists between the transport of bile acids (BA) in the liver and intestine; hepatic and intestinal BA transport can be evaluated and compared by using perfused liver and perfused intestine in the rabbit. The passive intestinal absorption is limited to the unconjugated BA, which occurs throughout the small bowel and colon, and is conditioned by the apical membrane lipid composition. A higher diffusion component is found in the terminal ileum compared to the jejunum, and seems to be related to the higher cholesterol-to-phospholipid ratio of the ileal brush border membranes. The active transport system is well characterized and the brush border membrane receptor, cytosolic BA binding proteins and basolateral anion exchange protein have been identified. Recently, the ileal BA transporter has been cloned from the hamster and human ileum and the main cytosolic BA binding protein was cloned from the rat ileum. In the liver, the active transport predominates on the passive diffusion both for conjugated and unconjugated BA. The maximal transport capacity in the liver is tenfold higher than in the intestine, while the Km values are of the same order of magnitude, i.e. in the millimolar range. Neither system operates at its maximum transport rate with prevalent concentrations of BA in portal blood or luminal content.
Animals↗
Improved intestinal absorption of an enteric-coated sodium ursodeoxycholate formulation.
A new enteric-coated formulation of sodium ursodeoxycholate was prepared and administered to man. The barrier film disintegrates and releases the drug only at pH > or = 5.5. The sodium salt of glycoursodeoxycholate was also prepared and encapsulated like ursodeoxycholate. Serum levels of ursodeoxycholate and glycoursodeoxycholate were measured by specific enzyme immunoassay after oral administration of their sodium salts in an enteric-coated formulation at equimolar doses of 475 and 540 mg. The same subjects also received in separate experiments ursodeoxycholic acid, sodium ursodeoxycholate, and glycoursodeoxycholic acid in gelatin capsules. The mean area under the curve (mumol/L.hr) following administration of enteric-coated sodium ursodeoxycholate (45 +/- 8) was significantly higher than that of either ursodeoxycholic acid (26 +/- 5; P < 0.01) or sodium ursodeoxycholate (25 +/- 6; P < 0.001) administered in a conventional gelatin capsule. No differences were found when glycoursodeoxycholic acid was administered as an enteric-coated sodium salt or in acid form in gelatin capsules. Ursodeoxycholic was administered at a dose of 10 mumol/min/kg over 1 hr to bile fistula rats both intraduodenally (i.d.) and intravenously (i.v.). The experiment included administration of the sodium salt in solution and the acid as a suspension. A similar experiment was performed with glycoursodeoxycholic acid. The ratio of the amount recovered from bile in the i.d. to that in the i.v. experiment is almost 1 for the sodium salt of ursodeoxycholate in solution, while it drops to 0.55 for ursodeoxycholic acid. No differences were found between i.v. and i.d. administration when glycoursodeoxycholic acid was administered in acid form and as a soluble sodium salt.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Hepatic uptake and intestinal absorption of bile acids in the rabbit.
The existence of transporters for bile acids (BA) in liver and intestine has been well documented, but information is still needed as to their respective transport capacity. In the present investigation, we compared the hepatic and intestinal transport rates for BA, using perfused livers and intestines. The livers and intestines were separately perfused and dose-response curves (0.25-10 mM) for tauroursodeoxycholate, taurocholate and taurodeoxycholate were obtained. The intestinal and mesenteric concentration and bile acid pattern were also evaluated in six non-fasting rabbits. Taurocholic, tauroursodeoxycholic and taurodeoxycholic acid ileal absorption showed saturation kinetics in the intestine as in the liver; the maximal uptake velocity for each bile acid in the liver was tenfold higher than the respective maximal transport velocity in the intestine; the Km values obtained in the liver were of the same order of magnitude, i.e. in the millimolar range. Taurocholic, tauroursodeoxycholic and taurodeoxycholic acid transport differences in the liver paralleled those in the intestine. Although the intestine was not homogeneously filled, the bile acid concentration in the ileal content fell into the range of the Km for the three studied bile acids, while the portal blood total bile acid concentration was inferior to the observed Kms of liver uptake. Therefore, both the hepatic and intestinal systems do not operate at their maximal transport rates at the prevailing concentrations in portal blood and luminal content, and the hepatic transport occurs at its highest efficiency (below the Km values) in physiological conditions.
Animals↗
Evaluation of the effect of rifaximin in colon diverticular disease by means of lactulose hydrogen breath test.
To understand better the mechanism by which rifaximin produces symptomatic relief in diverticular disease of the colon, the effect of this antibiotic on orocaecal transit time and on the production of hydrogen by intestinal microflora after ingestion of lactulose was studied in 33 patients with this disease and in 11 healthy subjects. An hydrogen breath test was carried out to measure pulmonary hydrogen excreted during the 3 hours after ingestion of 10 g lactulose. In patients, the hydrogen breath test with lactulose was repeated after treatment with 400 mg rifaximin twice daily for 10 days. In patients under basal conditions and controls, orocaecal transit time did not differ significantly, but hydrogen production was significantly higher in the former (p < 0.02). In patients, transit time and hydrogen excretion in response to lactulose administration did not differ significantly before and after treatment with rifaximin, and these two parameters were inversely correlated both before (r = 0.49, p < 0.01) and after rifaximin (r = 0.58, p < 0.001). Fifteen of the 33 patients showed accelerated transit time after treatment with the antibiotic, 10 showed no variation, and 8 showed prolonged transit. In 19 patients a reduction in hydrogen production was noted after rifaximin, while in 14 an increase was demonstrated. Twenty-one of the 33 patients reported an improvement in their symptoms with rifaximin; of these, only 10 showed accelerated transit time and 9 a reduction in hydrogen production after rifaximin.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Influence of ursodeoxycholic acid on biliary lipids.
The advent of bile acid therapy has shed some light on the mechanisms involved in determining bile lipid secretion. The administration of cholelytic bile acids results in a lowering of cholesterol percent molar and saturation index due to a reduction in cholesterol secretion. Studies carried out after administration of bile acids showed initially that biliary cholesterol secretion rates were dependent on the hydrophobic/hydrophilic balance of the prevailing bile acid present in bile. However, more detailed investigations showed that some bile acids (cholic and chenodeoxycholic acids) did not follow this rule because of the presence of other mechanisms involved in determining biliary cholesterol secretion and a possible link between cholesterol synthesis and biliary cholesterol secretion. Several different human models have been used in more recent studies to arrive at a better understanding of the mechanisms involved in determining bile lipid secretion: obese patients, obese patients in rapid weight loss, patients with non-familial hypercholesterolemia and primary biliary cirrhosis. The findings in these studies indicate how modifications in biliary lipid secretion can easily be induced when there are changes in the relative amounts of bile acids. These changes may bring about modifications in intestinal absorption, liver synthesis, and secretion of cholesterol and bile acids that could possibly lead to the formation of lithogenic bile and subsequently to cholesterol gallstones.
Bile Acids and Salts↗
Nutritional status affects the sensitivity to anoxia/reoxygenation in hepatocytes.
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Adenosine Triphosphate↗
[Consensus conference: therapy and prevention of biliary lithiasis].
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Cholelithiasis↗
Pseudotumoral appearance of a duodenal diverticulum by ultrasonography: a case report.
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Aged↗
Effect of simvastatin, ursodeoxycholic acid and simvastatin plus ursodeoxycholic acid on biliary lipid secretion and cholic acid kinetics in nonfamilial hypercholesterolemia.
It has been recently shown that the newest hypocholesterolemic agent, simvastatin, lowers the biliary cholesterol saturation index and that its association with ursodeoxycholic acid renders it more effective. To determine the mechanism by which simvastatin decreases the biliary cholesterol saturation index, we evaluated hepatic secretion rates of cholesterol, bile acids and phospholipids, and cholic acid pool size, turnover and synthesis in eight hyperlipidemic patients (five women and three men, age range = 38 to 65 yr). These assessments were conducted before treatment, after 4 wk of simvastatin (40 mg/day), after 4 wk of ursodeoxycholic acid (600 mg/day) and after a further 4 wk of a combination therapy of simvastatin (40 mg/day) plus ursodeoxycholic acid (600 mg/day). The cholesterol saturation index was significantly reduced with simvastatin (from 1.51 +/- 0.10 to 0.94 +/- 0.05, mean +/- S.E.; p less than 0.02), with ursodeoxycholic acid (from 1.51 +/- 0.10 to 0.86 +/- 0.03, mean +/- S.E.; p less than 0.02) and with the combination of simvastatin plus ursodeoxycholic acid (from 1.51 +/- 0.01 to 0.70 +/- 0.05, p less than 0.02). The cholesterol saturation index during combination therapy was significantly lower (p less than 0.02) than that reached during the use of simvastatin and ursodeoxycholic acid. Both simvastatin and ursodeoxycholic acid significantly reduced the hepatic secretion rate of cholesterol (from 130 +/- 14 mumols/hr to 81 +/- 12 mumols/hr, p less than 0.01, and 70 +/- 9 mumols/hr, p less than 0.01) without affecting bile acid and phospholipid outputs.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗