[An unusual cause of acute esophagitis].
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Biomedical subjects
Publications and source records attributed to A Gerolami.
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To test the role of nonmicellar phases in lipid absorption, intestinal uptake of fatty acids and cholesterol has been studied in vitro from supersaturated and micellar solutions. The micellar solubility limit at equilibrium was established for cholesterol and oleate/monoolein (2:1) at pH 6.7 with 10 mM taurocholate. Uptake by rat intestinal everted sacs was measured during incubation of 5 min. Cholesterol uptake increased linearly with the cholesterol content of micellar or supersaturated solutions up to a supersaturation of 150%. Oleate uptake, by contrast, remained essentially the same from either saturated or supersaturated (130-280%) mixtures. The difference between cholesterol and oleate uptake rates is explained by their distinct effects on micellar size, which is unchanged by cholesterol supersaturation but is increased by oleate. Solutions largely supersaturated (280%) with oleate-monoolein are polydisperse and contain viscous isotropic and paracrystalline phases similar to those observed during lipid absorption. These results suggest that, in the presence of such solutions, uptake occurs from both the micellar saturated and nonmicellar supersaturated phases.
The heparin-releasable neutral lipase (EC 3.1.1.3) from rat liver is inactivated by the common preparations of collagenases (EC 3.4.24.3) used for the isolation of liver cells. We show that two collagenases purified from Clostridium histolyticum allow both the complete preservation of this lipolytic activity and a good viability of liver cells isolated by the usual perfusion protocol.
The aim of our study was to define the mechanism by which cholesterol uptake is inhibited by lecithin but not by lysolecithin. The work compared the cholesterol uptake by everted rat jejunal sacs from bile salt-lecithin-cholesterol or bile salt-lysolecithin-cholesterol micelles. The micellar size and the cholesterol saturation were measured. The size or molecular weight increases when the lecithin concentration rises, and the cholesterol uptake decreases and leads to zero when the micelles contain more than 30% lecithin. The size of bile salt-lysolecithin-cholesterol micelles is smaller than that of lecithin micelles in comparable molar ratios. Consistent with this result is the fact that, for a given phospholipid concentration, cholesterol uptake is greater in the presence of lysolecithin than in the presence of lecithin. The diffusion rate of the micelles through the unstirred water layer decreases when micellar size increases. However, the comparison of uptakes from lecithin or lysolecithin micelles similar in size and in cholesterol saturation showed that the cholesterol uptake is still lower for lecithin micelles. This shows that with larger micelles some factor other than micellar size and cholesterol content of the micelles is important. We observe that lysolecithin absorption is 15-fold greater than lecithin absorption. We suggest that lysolecithin absorption results in a rapid supersaturation with cholesterol leading to cholesterol absorption.
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The relationship between alcohol consumption and the presence of seric hepatitis B virus markers has been studied in 125 male patients with liver cirrhosis and 126 control subjects. Mean daily alcohol consumption was found to be higher in patients than in controls. Hepatitis B virus seric markers were also more frequently observed in patients than in controls (53.6% vs. 36.5%, 2p less than 0.05). This was due to the greater frequency of hepatitis B core antibody alone or with hepatitis B surface antigen in the patients (2p less than 0.05). The possible interaction between alcohol and B virus was studied by log-linear hierarchic models for contingency tables. Data were displayed in a three-way classification frequency table (diagnosis, daily alcohol consumption, and hepatitis B virus seric markers). A model assuming that alcohol and seric markers of unresolved infection by hepatitis B virus are independently linked to cirrhosis gives the better goodness of fit between observed and estimated frequencies. The result however, suggests, that hepatitis B virus infection does not increase the influence of alcohol consumption on the production of cirrhosis.
The solubilizing powers of taurocholate, taurochenodeoxycholate and tauroursodeoxycholate for monoolein and cholesterol, and the size of the bile salt-monoolein-cholesterol micelles have been determined. For the three bile salt species, the micellar size depends on the saturation with monoolein. As a result, for a given bile salt to monoolein ratio, the taurochenodeoxycholate micelles are smaller than those of taurocholate and both are smaller than those of tauroursodeoxycholate. Intestinal cholesterol uptake has been studied in vitro as a function of the micellar size and the saturation degree with cholesterol. For a given bile salt to monoolein ration and 1) for low cholesterol concentrations, taurocholate leads to the greatest rates of uptake ; 2) for high cholesterol content, taurochenodeoxycholate induces the largest uptake. The specific micellar characteristics of the tauroursodeoxycholate micelles clearly demonstrate why this bile salt is of so little help in the intestinal uptake of cholesterol.
Cholesterol uptake by everted rat jejunal sacs is lower from mixed micelles containing tauroursodeoxycholate than from those with taurocholate or taurochenodeoxycholate. This occurs in spite of a greater saturation with cholesterol of tauroursodeoxycholate micelles as measured by equilibrium solubility studies. The results suggest that cholesterol saturation of solutions containing tauroursodeoxycholate is overestimated when calculated with reference to solubility in micellar form.
Cholesterol absorption was studied in mice receiving cholic, chenodeoxycholic, or ursodeoxycholic acids (0.2% of the diet) for 2 months. Cholesterol absorption was greater with cholic acid (79%) than with chenodeoxycholic acid feeding (60%) and the lowest levels were observed during ursodeoxycholic acid feeding (37%). Under the three diets, bile acid pool and bile acid secretion were not different. Biliary cholesterol secretion was increased by cholic acid. The bile acid fed represents at least 80% of total bile acids. Micellar solubilization of oleic acid and cholesterol in the presence of each tauro-conjugated bile salt (10 mM) was determined in vitro by the coprecipitation method. Whatever the pH conditions, taurochenodeoxycholate solubilized significantly more cholesterol and more oleic acid than taurocholate. Tauroursodeoxycholate had the poorest detergent properties for both lipids. The differences between the three bile salts for cholesterol solubilization were enlarged by lowering pH and by high oleic acid concentration. Therefore the decrease in cholesterol absorption observed during ursodeoxycholic acid feeding could be explained by the poor detergent properties of this bile salt species. On the other hand, there is no relationship between the detergent properties of taurochenodeoxycholate and taurocholate and their effects on cholesterol absorption in mice. These results suggest that, in this particular case, micellar solubilization is not the rate limiting step in cholesterol absorption.
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Five groups of 20 mice received for 4 months one of the following diets: T, standard diet (T); a, T + cholic acid (0.2%); b, T + cholic acid (0.2%) + beta-sitosterol (2%); c, T + chenodeoxycholic acid (0.2%); d, T + chenodeoxycholic acid (0.2%) + beta-sitosterol (2%). After this time, the cholesterol intestinal absorption and the biliary secretion of lipids were measured. The biliary secretion of cholesterol, the total hepatic cholesterol (23 mg/g liver dry weight), and the intestinal absorption of cholesterol (90% administered dose) were higher in mice fed with cholic acid than in mice fed with chenodeoxycholic acid (hepatic cholesterol, 9.6 mg/g liver dry weight; absorption, 65% administered dose). The addition of beta-sitosterol to the diet supplemented with cholic acid decreased the cholesterol intestinal absorption and the biliary secretion of cholesterol so that both became similar to that obtained with chenodeoxycholic acid. These results indicate that in mice, as in man, cholic acid elicits a higher cholesterol biliary secretion than chenodeoxycholic acid. In this experimental model, the distinct effect on the biliary cholesterol of these two bile salts is due to their specific effects on the intestinal absorption of cholesterol.
Micellar cholesterol solubilities in bile salt-monoolein-oleic acid systems have been determined. Whatever the bile salt/oleyl compounds ratio, taurochenodeoxycholate solubilizes more cholesterol than taurocholate and much more than tauroursodeoxycholate. At pH 6.7, the cholesterol solubility limit is about the same with either oleate or monoolein. Cholesterol solubility falls in oleate-bile acid mixtures as the pH is raised. The capacity for supersaturation with cholesterol is greater for bile salt-monoolein than for bile salt-oleate micelles. For the latter it decreases as pH increases.
The biliary elimination of glycodihydrofusidate (GDHF), a structural analogue of bile salts, was studied in bile fistula rats. GDHF was excreted in bile with a maximal excretory rate (Tm = 0.80 mumol min-1 kg-1) which is much lower than bile salts Tm. The effects of dehydrocholate and taurocholate on GDHF biliary secretion suggest a stimulatory effect of bile salts on canalicular excretion of the drug. (a) When a bolus intravenous injection of 3 mumol of GDHF was followed after 2 min by a continuous dehydrocholate perfusion (10 mumol min-1 kg-1), biliary excretion of GDHF was increased in comparison with control rats. (b) Upon attaining the biliary Tm by continuous perfusion of GDHF at a rate of 1.35 mumol min-1 kg-1, infusion with either taurocholate or dehydrocholate increased its Tm to a similar degree. These results are similar to those previously obtained with the effects of bile salt infusions on the Tm of bromosulfophthalein. They suggest therefore that hepatic transport of GDHF and bile salts occurs by routes which are distinct for canalicular transport in spite of the striking structural similarities between GDHF and bile salts.
In France, changes in the incidence of gallstones during the 20 years following World War II paralleled the changes in total calories, protein and lipid of the diet. The incidence of gallstones in autopsy statistics has been compared to the diets in different countries: France, India, Japan, Portugal, South Africa, Sweden and Uganda. Low calorie, low protein, low lipid intake and vegetable diet are associated with a low incidence of gallstones. A positive correlation between calorie intake and gallstones incidence was found at necropsy for calorie intakes lower than 3,000 kcal. In countries with high calorie, high protein and high lipid intakes, such a correlation was not found. These results suggest that a hypocaloric diet associated with a low intake of fat and protein mostly of vegetable origin, is protective against cholelithiasis.
In a first study, a population of 1,045 women from 20 to 61 years old has been studies. 24 (2.3%) were known to have gallstones. After excluding these 24 cases, 214 were drawn from the same population and accepted an oral cholecystography. 11 cases of stones (5.1%) were discovered. The diet of these 11 patients and of the 202 women without gallstones was not significantly different. In a second study, the diet of 50 patients with known gallstones and the diet of 50 matched controls have been compared. No significant difference between the two groups can be demonstrated for calories, protein, fat or carbohydrates intake. These results are compared to previous results which showed overconsumption of food in gallstone patients. The method for all studies being similiar, it seems that the dietetic factors are now less important in cholesterol stones pathogenesis than during the period which followed the second world war starvation in southeast France. The assumption that undernutrition diminishes the chance for a women to develop gallstones is proposed.
Incorporation of [1(14)-C] acetate into cholesterol by subcellular particles from the liver and the small intestine of rats with a biliary diversion and a duodenal perfusion of sodium taurocholate, taurochenodeoxycholate or taurodehydrocholate, was studied in vitro. In the liver, taurochenodeoxycholate prevented the increase of cholesterol synthesis induced by biliary drainage. Taurocholate had no action on cholesterol synthesis at any time, day or night. Intestinal synthesis of cholesterol was reduced by taurocholate and taurochenodeoxycholate but was not modified by taurodehydrocholate infusion.
134 patients with radiolucent gallstones were randomly allocated to receive either placebo or 1 of 3 different doses of chenodeoxycholic acid (CDCA); 750, 1,500, or 3,000 mg). The initial dose was lowered if not well tolerated. 107 patients were treated for more than 3 months. Among them, stones dissolved in 21 and were smaller in 25 patients. Partial or complete dissolution occurred in 4 of the 13 receiving 375 mg/day, 14 of 37 receiving 750 mg, 24 of the 38 receiving 1,500 mg and 4 of 8 receiving 3,000 mg/day. The number of responders to the therapy was significantly greater in the groups of patients receiving 1,500 mg/day or 17-24 mg/kg body weight than in any other group. However, side effects, i.e., diarrhea and transaminase increase, are also dose related. It appears from this study that the optimal dose of CDCA may be between 17 and 20 mg/kg body weight.
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