Carmen Covarrubias

Influence of legume intake on biliary lipids and cholesterol saturation in young Chilean men: Identification of a dietary risk factor for cholesterol gallstone formation in a highly prevalent area*

Chileans and North American Indians have one of the highest prevalence rates of cholesterol gallstones in the world. The most common theory to explain this has been the operation of some as yet undefined genetic risk factor in these populations. Searching for some common environmental factor for gallstones in Chileans and North American Indians, we found that beans and other legumes are common foods consumed by both populations. In this study we tested the hypothesis that legume intake may favor the production of biliary cholesterol supersaturation. We studied 20 young men subjected to a diet containing 120 g/day of legumes and a control diet without legumes for a period of 1 mo each. Both diets supplied identical quantities of energy, carbohydrates, protein, total fat, fiber, and cholesterol. Low-density lipoprotein cholesterol concentration decreased by 16% (p less than 0.001) after the legume diet. Biliary cholesterol saturation increased in 19 of the 20 subjects; the mean of the group markedly increased from 110% to 169% (p less than 0.001) after the legume diet. These results are consistent with the hypothesis that legume intake is a potential risk factor for cholesterol gallstone disease.

Reversal of progesterone-induced biliary cholesterol output by dietary cholesterol and ethynylestradiol

The significant increment of biliary cholesterol output induced by the subcutaneous injection of 40 mg/kg body wt. of progesterone to male rats was reversed either by feeding a 1% cholesterol diet or by injecting three daily doses of 2 mg/kg ethynylestradiol. These last two experimental manipulations significantly decreased biliary cholesterol saturation from 44 +/- 4% (progesterone) to 30 +/- 3% (progesterone +1% cholesterol diet) and 23 +/- 0.5% (progesterone + ethynylestradiol) under circumstances of minor changes in the rates of biliary bile salt and phospholipids outputs. The rate of the microsomal acyl-CoA:cholesterol acyltransferase and the concentration of microsomal cholesterol esters significantly increased more than 100% in both cholesterol-fed and estradiol-injected rats. The rate of biliary cholesterol output was reciprocally correlated with both microsomal cholesterol ester concentration of livers (r = -0.47, P less than 0.01) and the activity of the hepatic acyl-CoA:cholesterol acyltransferase (r = -0.58, P less than 0.005) in a series of rats injected with progesterone, with progesterone +1% cholesterol diet and with progesterone + estradiol. No correlation was found between the rate of biliary cholesterol output and the concentration of microsomal free cholesterol. These experiments demonstrate the existence of a close and reciprocal relationship between the rate of biliary cholesterol output and the rate at which the liver esterifies cholesterol.

Apolipoprotein E polymorphism in patients with acute pancreatitis.

We have shown that patients with previous acute pancreatitis (AP) may have an abnormal catabolism of chylomicron remnants (CMR). Because apoprotein E (Apo E) genetic polymorphism has an important influence on CMR clearance, we compared frequency distribution of Apo E phenotypes in 52 patients with AP, 109 patients with gallstones, and 110 control subjects. Apo E phenotypes were detected by isoelectric focusing and immuno-blotting. After adjusting for differences in age and gender, fasting triglyceride level was comparable between the study groups. The frequency distribution of Apo E phenotypes was not different between the three study groups and it was in Hardy-Weinberg equilibrium. The gene frequency for Apo E2 was 0.212, 0.273, and 0.243 in AP, gallstone, and control group, respectively. For Apo E3 it was 0.701, 0.627, and 0.674, and for Apo E4 0.090, 0.100, and 0.083 in the same groups, respectively. Differences were not statistically significant (x2). In conclusion, the abnormal catabolism of CMR in patients with AP is not attributable to Apo E polymorphism. An alternative explanation may be sought in the activity of the recently identified hepatocytic Apo E receptor [LDL-related receptor protein (LRP)].

Pregnancy and Cholelithiasis: Pathogenesis and Natural Course of Gallstones Diagnosed in Early Puerperium

Several recent reports have indicated an increased prevalence of gallstones in association with pregnancy. If these reports are true, the early puerperium should be a favorable time to detect the disease in its initial stages and follow its natural course. Accordingly, the gallbladder was examined by ultrasound in 980 women during the immediate postpartum period and in 150 nulliparous, age-matched healthy volunteers. Gallstones were detected in 12.2% of the puerperal women and in 1.3% of the control group. In 70 patients who had stones in a functioning gallbladder, 22 (31%) had had attacks of biliary colic. The history of pain was more common in patients with stones greater than 10 mm in diameter. Forty-one women with small stones (< 10 mm) were followed clinically and ultrasonographically for between 6 and 24 (mean = 8.7) mo. All remained pain-free, and in twelve subjects (29%) the stones disappeared. Gallbladder bile was examined in 11 normal volunteers (controls) immediately after delivery and in 19 women with small stones 39 +/- 6 days postpartum. Bile was saturated with cholesterol in the controls and was unsaturated in patients with gallstones. We conclude that in our population pregnancy is a very important pathogenetic factor favoring gallstone formation. Attacks of biliary colic appear early and frequently in young Chilean women with this disease. Unexplained disappearance of small stones frequently occurs: in some cases it is likely to be the result of spontaneous dissolution because bile becomes unsaturated within a few weeks of delivery.