1/11. Hyperabsorption and retention of campestanol in a sitosterolemic homozygote: comparison with her mother and three control subjects.We measured the percent absorption, turnover, and distribution of campestanol (24-methyl-5alpha-cholestan-3beta-ol) in a sitosterolemic homozygote, her obligate heterozygous mother, and three healthy human control subjects. For reasons relating to sterol hyperabsorption, the homozygote consumed a diet low in plant sterols that contained campestanol at about 2 mg/day. The heterozygote and three control subjects were fed a diet supplemented with a spread that contained campestanol at 540 mg/day and sitostanol (24-ethyl-5alpha-cholestan-3beta-ol) at 1.9 g/day as fatty acid esters. plasma campestanol concentrations determined by capillary gas-liquid chromatography were 0.72 /- 0.03 mg/dl in the homozygote, 0.09 /- 0.04 mg/dl in the heterozygote, and 0.05 /- 0.03 mg/dl for the control mean. After simultaneous pulse labeling with [3alpha-(3)H]campestanol intravenously and [23-(14)C]campestanol orally, the maximum percent absorption measured by the plasma dual-isotope ratio method as a single time point was 80% in the homozygote, 14.3% in the heterozygote, and 5.5 /- 4.3% as the mean for three control subjects. Turnover (pool size) values estimated by mathematical analysis of the specific activity versus time [3alpha-(3)H]campestanol decay curves were as follows: 261 mg in the homozygote, 27.3 mg in the heterozygote, and 12.8 /- 7.6 mg in the three control subjects (homogygote vs. controls, P < 0.001). The calculated production rate (mg/24 h) equivalent to actual absorption in the presence of dietary sterols and stanols was 0.67 mg/day or 31% of intake in the homozygote, 2.1 mg/day or 0.3% of intake in the heterozygote, and 0.7 /- 0.3 mg/day or 0.1% of intake in the three control subjects. However, the excretion constant from pool A (K(A)) was prolonged markedly in the homozygote, but was 100 times more rapid in the heterozygote and three control subjects.Thus, campestanol, like other noncholesterol sterols, is hyperabsorbed and retained in sitosterolemic homozygotes. However, campestanol absorption was only slightly increased in the sitosterolemic heterozygote and removal was as rapid as in control subjects.- - - - - - - - - - ranking = 1keywords = plant (Clic here for more details about this article) |
2/11. Tuberous xanthomas in sitosterolemia.Sitosterolemia is an autosomal recessive lipid disorder in which plasma plant sterol levels are extremely elevated and cholesterol levels are often elevated but may be normal. Clinically sitosterolemia is characterized by xanthomas, premature vascular disease, and arthritis. adolescent boys and girls with sitosterolemia are susceptible to fatal cardiac events. Dermatologists may have a vital role in the diagnosis of this rare but serious condition because early detection and treatment are important in preventing the associated atherosclerotic heart disease. We present a 7-year-old girl with sitosterolemia and tuberous xanthomas.- - - - - - - - - - ranking = 1keywords = plant (Clic here for more details about this article) |
3/11. Japanese sisters associated with pseudohomozygous familial hypercholesterolemia and sitosterolemia.Pseudohomozygous familial hypercholesterolemia is a rare condition of unknown etiology. Sitosterolemia is a rare autosomal recessively inherited disorder that is characterized by premature coronary artery disease, cutaneous xanthomas, and increased plasma plant sterols and 5alpha-stanols. Only a few cases of both sitosterolemia and pseudohomozygous familial hypercholesterolemia have been reported. In this study, we report two sisters with both conditions. With a low-cholesterol diet (< 250 mg/day), serum cholesterol concentration decreased rapidly to an almost normal level and cutaneous xanthomas gradually regressed and finally disappeared; however, plant sterol levels did not change during the period. Plant sterols should be measured in patients considered to have pseudohomozygous familial hypercholesterolemia. The two conditions in this family may have been the results of a single gene mutation. The findings also indicate that low cholesterol diet therapy is effective for the treatment of hypercholesterolemia but not of sitosterolemia in this family.- - - - - - - - - - ranking = 2keywords = plant (Clic here for more details about this article) |
4/11. A 19-year-old man with myocardial infarction and sitosterolemia.This is a case report of a 19-year-old man who presented with acute myocardial infarction with obstruction of one coronary artery and rapid progression to three vessels in 8 months. He was proved to have sitosterolemia, a rare hereditary disease with plant sterol storing, resulting in juvenile coronary artery disease. Atherosclerotic complications can be preventable by administration of bile acid-binding resin, after the correct diagnosis is made. We introduce this disease with a review of the literature.- - - - - - - - - - ranking = 1keywords = plant (Clic here for more details about this article) |
5/11. Transcutaneous implantation of an internal cardioverter defibrillator in a small infant with recurrent myocardial ischemia and cardiac arrest simulating sudden infant death syndrome.This report describes the implantation of a transcutaneous ICD system using a small patch electrode in the subscapular position, and an active-can device in a 5.3-kg infant. The indication for ICD implantation was recurrent cardiac arrest in the presence of normal coronary anatomy. Metabolic evaluation suggested a defect in fatty acid oxidation.- - - - - - - - - - ranking = 6keywords = plant (Clic here for more details about this article) |
6/11. liver transplantation in a patient with sitosterolemia and cirrhosis.Sitosterolemia (MIM 210250) is a rare genetic disorder caused by disruption of the normal mechanisms that regulate dietary cholesterol absorption and prevent the accumulation of noncholesterol sterols. As a result of this defect, affected individuals accumulate high concentrations of plant sterols in plasma and tissues. They present clinically with tendon or tuberoeruptive xanthomas, premature coronary artery disease, and/or hemolytic anemia. Two genes, ABCG5 and ABCG8, compose the STSL locus, and complete mutation in either, but not both, results in disease. The expression of these genes is confined to the intestine and liver. They are thought to function as sterol efflux pumps. It is not clear which organ, liver or intestine, is of greater importance in maintaining sterol balance with respect to noncholesterol sterols. We report here a case of a patient who presented with "chronic active liver disease" and was found to have sitosterolemia by chance and subsequently underwent orthotopic liver transplantation. Following transplantation, the grossly elevated pretransplantation serum plant sterol levels decreased to values only slightly higher than those of the patient's heterozygous father. This case highlights 2 important features: (1) The liver functions as the predominant organ for maintaining noncholesterol sterol balance (because the intestinal defect was not altered), and (2) a new clinical feature of undiagnosed sitosterolemia may be "idiopathic" liver disease. Because the diagnosis of sitosterolemia is based on specialized plasma analyses, we would propose that some consideration to this diagnosis should be given in appropriate cases.- - - - - - - - - - ranking = 9keywords = plant (Clic here for more details about this article) |
7/11. Decreased cholesterol biosynthesis in sitosterolemia with xanthomatosis: diminished mononuclear leukocyte 3-hydroxy-3-methylglutaryl coenzyme a reductase activity and enzyme protein associated with increased low-density lipoprotein receptor function.We investigated the mechanism for reduced cholesterol biosynthesis in sitosterolemia with xanthomatosis. The conversion of acetate to cholesterol and total and active hydroxymethylglutaryl (HMG) coenzyme a (CoA) reductase activities, enzyme protein mass, and catalytic efficiency were related to low-density lipoprotein (LDL) receptor function in freshly isolated mononuclear leukocytes collected at 9 AM after a 12-hour fast from two affected sisters and 12 control subjects. Active HMG-CoA reductase activity was determined in mononuclear leukocyte microsomes prepared and assayed in the presence of sodium fluoride, while total HMG-CoA reductase activity was determined in the absence of the phosphatase inhibitor. Enzyme protein was assayed using rabbit polyclonal anti-rat liver microsomal HMG-CoA reductase serum. The rates at which [14C]acetate was transformed to cholesterol by sitosterolemic mononuclear leukocytes were decreased 29% and 41%, respectively, compared with the mean value for mononuclear leukocytes from 12 control subjects. Similarly, total HMG-CoA reductase activities were 71% and 68% lower in sitosterolemic mononuclear leukocyte microsomes and were associated with 62% and 65% less enzyme protein than the mean for the control microsomal preparations. This marked decrease in HMG-CoA reductase protein mass in sitosterolemic microsomes was partially compensated for by an increase in the proportion of active enzyme. Sitosterolemic plasma and mononuclear leukocyte cholesterol concentrations were not significantly different from control values, although total sterol levels were increased about 20% because of abundant plant sterols. In contrast, receptor-mediated LDL degradation by sitosterolemic mononuclear leukocytes was increased 50% over control.(ABSTRACT TRUNCATED AT 250 WORDS)- - - - - - - - - - ranking = 1keywords = plant (Clic here for more details about this article) |
8/11. The presence of 5 alpha-sitostanol in the serum of a patient with phytosterolemia, and its biosynthesis from plant steroids in rats with bile fistula.The presence of 5 alpha-sitostanol (24-ethyl-5 alpha-cholestan-3 beta-ol) in serum of a patient with the rare genetic disease phytosterolemia was confirmed. This study aimed at clarifying the pathway(s) for the formation of 5 alpha-sitostanol, by use of rats with bile fistula. 5 alpha-Sitostanol was formed only slowly from sitosterol, but readily from 24-ethyl-4-cholesten-3-one. Some conversion was also obtained with 7 alpha-hydroxysitosterol as precursor. In view of the low rate of 7 alpha-hydroxylation of sitosterol, however, a pathway from sitosterol to 5 alpha-sitostanol involving 7 alpha-hydroxysitosterol as intermediate is probably of small physiological importance. Intestinal microorganisms are not essential for the above conversions, since the 5 alpha-sitostanol was found in bile from bile fistula rats. 5 alpha-Sitostanol was converted to water soluble metabolites (bile acids) much more slowly than was cholestanol (5 alpha-cholestan-3 beta-ol), and was accumulated serum to a much larger extent.- - - - - - - - - - ranking = 4keywords = plant (Clic here for more details about this article) |
9/11. Lethal atherosclerosis associated with abnormal plasma and tissue sterol composition in sitosterolemia with xanthomatosis.Tissue sterol composition was determined in an 18-year-old male with sitosterolemia with xanthomatosis who died suddenly and whose coronary and aortic vessels showed extensive atherosclerosis and, for comparison, in an 18-year-old male with minimal atherosclerosis who died accidently. Sterols in the control tissues (plasma, erythrocytes, cardiac muscle, lung, liver, aorta, and brain) contained cholesterol with only trace amounts of cholestanol. In contrast, sterols in corresponding tissues of the sitosterolemic subject (except brain) were composed of cholesterol, increased amounts of plant sterols, campesterol and sitosterol, and 5 alpha-saturated stanols, cholestanol, 5 alpha-campestanol, and 5 alpha-sitostanol, that were deposited in approximately the same ratio as present in plasma. However, sitosterolemic brain sterol composition resembled that of the control brain with cholesterol and only trace amounts (less than 1%) of cholestanol and phytosterols. The sitosterolemic aorta was extensively atherosclerotic and contained more than twice the quantity of sterols as the control aorta (5.6 mg/g versus 2.6 mg/g) with increased amounts of cholesterol, plant sterols, and 5 alpha-saturated stanols. These results indicate that cholesterol, plant sterols, and 5 alpha-stanols are deposited prematurely and are associated with accelerated atherosclerosis in subjects with sitosterolemia with xanthomatosis.- - - - - - - - - - ranking = 3keywords = plant (Clic here for more details about this article) |
10/11. A marked and sustained reduction in LDL sterols by diet and cholestyramine in beta-sitosterolemia.This study examines the therapeutic outcome of a low plant sterol diet and adjunctive drug therapy (cholestyramine) in the long term treatment of beta-sitosterolemia. A diet restricted in plant sterols, cholesterol and fat was implemented in a 48-year-old male beta-sitosterolemic patient. The plant sterols beta-sitosterol, campesterol and stigmasterol, and cholesterol content of the diet were quantitated by a gas chromatography method (GLC) during metabolic ward studies. food table analysis of dietary sterols, while quantitatively similar to GLC, significantly underestimated the level of plant sterols and therefore overestimated dietary cholesterol intake. The duration of the study was 18 months. The effect of the diet over a period of 6 months on the sterol levels of plasma and individual lipoprotein fractions (VLDL, LDL, HDL) was evaluated. apolipoproteins a-1 and B-100 levels were measured. The same parameters were assessed over the next 12 months with the adjunctive use of cholestyramine and dietary restrictions. The diet was effective in lowering total, VLDL, and LDL plant sterols by 37%, 59%, and 32% respectively. The low plant sterol diet did not change total plasma, VLDL or LDL cholesterol. With the addition of cholestyramine, total plasma and LDL cholesterol declined by 64 and 76%, respectively, while HDL-cholesterol remained unchanged. LDL plant sterols declined by 77%, while VLDL plant sterol showed no further change. The decline showed no discrimination among the individual plant sterols. One week after cholestyramine therapy, apolipoprotein B fell from 1.03 to 0.11 g/L, while apolipoprotein A rose from 1.29 to 1.79 g/L. These levels subsequently stabilized at 70% below (0.29 g/L) and 42% above (1.81 g/L) that of diet therapy alone. Xanthomas, angina pectoris, and intermittent claudication resolved during the diet and cholestyramine therapy period. Dietary restriction of plant sterols combined with cholestyramine therapy is an effective means of treating beta-sitosterolemia.- - - - - - - - - - ranking = 10keywords = plant (Clic here for more details about this article) |
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