O. Leiss

Effect of low-dose sitostanol on serum cholesterol in patients with hypercholesterolemia

Sitostanol (24-ethyl-5 alpha-cholestan-3 beta-ol), a hydrogenated derivative of sitosterol, was administered in a low dose (1.5 g/day) for 4 weeks to 6 patients with hypercholesterolemia. Total cholesterol was reduced significantly after 3 and 4 weeks by 10 and 15%, respectively. The reduction of total cholesterol was entirely due to a fall in LDL cholesterol. Total triglycerides and HDL cholesterol were not altered. Two weeks after cessation of sitostanol administration serum cholesterol returned to pretreatment levels. No significant amounts of sitostanol could be detected in plasma during therapy. These results suggest that low-dose sitostanol might be a useful hypolipidemic agent for the treatment of mild hypercholesterolemia.

Different effects of chenodeoxycholic acid and ursodeoxycholic acid on serum lipoprotein concentrations in patients with radiolucent gallstones.

The effect on serum lipoprotein concentrations of chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA) was examined in eight normolipemic patients with radiolucent gallstones during constant liquid formula infusion into the duodenum. Every patient received each bile acid (1000 mg/day) during two consecutive randomized 4-week periods. During treatment with CDCA but not UDCA, the serum triglycerides decreased by an average of 26%. Mean HDL cholesterol decreased by 46% during CDCA therapy and remained unchanged during UDCA administration. Simultaneous measurements of biliary lipid secretion showed a significant negative correlation between HDL cholesterol concentration and hepatic secretion of CDCA (r = -0.652) and a positive correlation between the LDL cholesterol/HDL cholesterol ratio and hepatic secretion of CDCA (r = 0.840). Despite their close chemical relationships and similar effects on biliary lipids, CDCA and UDCA differ markedly in their effects on serum lipoproteins. Because of this and minor side effects, UDCA seems to be a safer agent than CDCA for cholesterol gallstone dissolution.

Effect of short-term treatment with bezafibrate and fenofibrate on biliary lipid metabolism in patients with hyperlipoproteinaemia

Abstract. Sixteen patients with different types of hyperlipoproteinaemia were treated with the clofibrate analogues, bezafibrate or fenofibrate. Serum lipids and lipid composition of gallbladder bile were measured before and after 3–4 weeks of treatment. Both bezafibrate and fenofibrate reduced serum lipids effectively but increased the lithogenic index of bile from 1·11 to 1·47 and 1·25 to 1·80 (P < 0·01), respectively, by increasing molar percent of cholesterol and decreasing molar percent of bile acids. Measurements of biliary lipid secretion in three patients before and after bezafibrate administration revealed a marked and significant increase in cholesterol secretion (from 119 to 166, from 58 to 128, and from 149 to 172 μmol h‐1, respectively; P < 0·05) without altering bile acid and phospholipid output. These results indicate that bezafibrate and fenofibrate exhibit the same effect on biliary lipid metabolism as clofibrate and might therefore induce cholesterol gallstone disease.

Biliary cholesterol saturation in non‐obese women and non‐obese men before and after puberty

Abstract. The lipid composition of gallbladder bile was determined in forty‐seven normal, non‐obese subjects (twenty females and twenty‐seven males) without gallstones ranging in age from seven months to twenty‐nine years. Before puberty, bile was undersaturated with cholesterol in both sexes to the same extent. After puberty a marked increase in cholesterol saturation was observed in females but not in males (138%vs 88%; P<0·01). A significant correlation between age and cholesterol saturation could be observed in females (r=0·546; P<0·05) but not in males.

Increased prevalence of apolipoprotein E2 in patients with retinitis pigmentosa

Apolipoprotein E isoforms were determined in 139 unrelated patients with retinitis pigmentosa (RP). When compared to prevalence rates for the general population in Germany, an increased prevalence was observed for phenotypes E2/E2: 10.1 vs. 1.0% (p less than 0.001), E2/E3: 19.4 vs. 12.0% (p less than 0.05), and E2/E4: 5.8 vs. 1.5% (n.s.), while the prevalence appeared to be reduced for phenotypes E3/E3: 48.9 vs. 59.8% (n.s.) E3/E4: 13.7 vs. 22.9% (p less than 0.05), and E4/E4: 2.2 vs. 2.8% (n.s.). These findings suggest that genetically determined abnormalities of plasma lipoprotein metabolism may be associated with some forms of RP.

Effects of phenobarbital on biliary lipid metabolism in children with chronic intrahepatic cholestasis.

The effects of phenobarbital (5.4–7.5 mg/kg body weight) for 14 days were studied in four children with severe intrahepatic cholestasis (group I) and in four with a syndromatic type of paucity of intralobular bile ducts (group II). Phenobarbital administration resulted in a moderate improvement of pruritus in all patients. There was a significant decrease of bilirubin in serum (group I: from 4.8 to 2.7 mg/dl; group II: from 6.1 to 2.1 mg/dl); total bile acids (group I: from 416 to 337 μmol/l; group II: from 156 to 123 μmol/l) and cholesterol (group I: from 248 to 207 mg/dl; group II: from 351 to 292 mg/dl). Alkaline phosphatase activity increased from 929 to 1126 U/l in group I and from 1751 to 2360 U/l in group II. SGOT and SGPT activities remained unchanged in both groups. In group I total biliary lipid concentration and bile acid output increased from 0.09 to 0.17 g/dl and from 3.9 to 7.2 μmol/kg per 30 min, respectively. Molar percentages of cholesterol, phospholipids and bile acids in bile remained unchanged. In group II total lipid concentrations and bile acid output increased from 1.62 to 2.0 g/dl and from 27.8 to 39.1 μmol/kg per 30 min, respectively. The molar percentage of cholesterol decreased from 5.6 to 3.5 mol%.The present results indicate that short term administration of phenobarbital has only minimal effects on biliary lipid metabolism in children with chronic intrahepatic cholestasis.

Lipid composition of human aqueous humor

The lipid composition of human aqueous humor was determined in ten samples from patients undergoing cataract surgery. The mean concentration was 16.4 mg/dl for total lipids, 2.5 for phospholipids, 1.1 for free fatty acids, 1.7 for unesterified cholesterol 2.0 for triglycerides, and 9.0 mg/dl for cholesterol esters, respectively. The presence of lipids in aqueous humor suggests that lipids are transported through the human aqueous humor.

Biliary lipid metabolism in children with chronic intrahepatic cholestasis

Biliary lipid composition, standard liver function tests, serum lipids and faecal fat excretion were studied in 15 children with chronic intrahepatic cholestasis (severe intrahepatic cholestasis, n=6; paucity of intralobular bile ducts, n=4; benign recurrent cholestasis, n=5) and compared to 15 children without gastrointestinal diseases. Severe and benign intrahepatic cholestasis were associated with normal or moderately elevated serum lipids. Biliary lipid concentrations were extremely reduced, bile acid concentrations were below the critical micellar concentration. This may account for the high incidence of gallstone formation in these patients. Remission periods in patients with benign recurrent cholestasis were not followed by complete normalisation of biliary lipid concentrations, indicating a primary defect in hepatic excretory function. Children with paucity of intralobular bile ducts showed markedly increased serum lipids, but only a two-fold reduction in biliary lipid concentrations. Cholic acid was the predominant bile acid in bile of all cholestatic children even during remission. Neither increased levels of monohydroxy bile acids nor unusual bile acids could be identified in notable amounts.