Biomedical subjects

Y Ringel

Publications and source records attributed to Y Ringel.

10 recordsLinked to original sources

PubMed1998

Fluctuations of lipid and lipoprotein levels in hyperlipidemic postmenopausal women receiving hormone replacement therapy.

BACKGROUND: Fluctuations in lipid and lipoprotein levels are encountered quite often in hyperlipidemic patients. We examined the possibility that lipid and lipoprotein levels fluctuate due to the different effects of estrogen and progestogen in postmenopausal hyperlipidemic women receiving combined hormonal replacement therapy. METHODS: In an open-label study conducted during 3 consecutive hormonal cycles (3 months), levels of fasting total cholesterol, triglycerides, and low (LDLC)- and high-density lipoprotein cholesterol (HDLC) were determined in 36 postmenopausal hyperlipidemic women on day 13 of conjugated equine estrogen (1.25 mg/d) therapy and on day 25 after 12 days of receiving estrogen plus medroxyprogesterone acetate (5 mg/d). RESULTS: While receiving estrogen and combined therapies, means +/- SD total cholesterol levels increased from 6.50 +/- 0.97 mmol/L (251 +/- 37 mg/dL) to 6.88 +/- 1.42 mmol/L (266 +/- 54 mg/dL) (P<.001); LDLC levels, from 4.05 +/- 1.14 mmol/L (156 +/- 44 mg/dL) to 4.62 +/- 1.36 mmol/L (178 +/- 52 mg/dL) (P<.001). Mean +/- SD HDLC cholesterol levels decreased from 1.44 +/- 0.32 mmol/L (55 +/- 12 mg/dL) to 1.29 +/- 0.28 mmol/L (50 +/- 10 mg/dL) (P<.001); triglyceride levels, from 2.23 +/- 1.03 mmol/L (197 +/- 91 mg/dL) to 2.06 +/- 1.04 mmol/L (182 +/- 92 mg/dL) (P<.001). CONCLUSIONS: Hyperlipidemic postmenopausal women receiving combined sequential estrogen and progestogen replacement therapy demonstrate very significant fluctuations in their lipid and lipoprotein levels. These fluctuations depend on the hormonal phase, ie, estrogen alone or combined with progestogen.

Estrogen Replacement Therapy↗

PubMed1998

Increased saturation of the fatty acids in the sn-2 position of phospholipids reduces cholesterol crystallization in model biles.

Changes in the molecular structure of biliary phospholipids were shown to have major effects on cholesterol solubility, carriers and crystallization in human and model biles. This study investigated systematically the effects of varying saturation of the phosphatidylcholine (PC) sn-2 fatty acid on the cholesterol crystallization process in 3 different model biles. Twenty % of the egg PC (EPC) in these biles were replaced by synthetic PC's with 16:0-18:0, 16:0-18:1, or 16:0-18:2 fatty acyl chains. With 18:0 in the sn-2 position, the crystal observation time (COT) was prolonged from 2 days in the control EPC solution to 14 days (p<0.05). The crystal growth rate (CGR) was reduced from 0.1 OD/day to unmeasurable levels, and the total crystal mass on day 14 decreased by 86%. The introduction of one (18:1), and two (18:2) double bonds in the sn-2 fatty acid rapidly reversed these effects. Ultracentrifugal analysis showed precipitable cholesterol as monohydrate crystals. In the 16:0-18:0 test solution, most of the precipitable cholesterol remained in the supersaturated multilamellar vesicles. Saturation of the biliary PC sn-2 fatty acyl chain prolongs the COT, slows the CGR, reduces the crystal mass, and extends cholesterol solubility in multilamellar vesicles. Desaturation of the sn-2 fatty acid reverses these effects.

Bile↗

PubMed1998

The effects of phospholipid molecular species on cholesterol crystallization in model biles: the influence of phospholipid head groups.

BACKGROUND/AIMS: Variations in the molecular species of biliary phospholipids have been shown to exert major effects on cholesterol solubility and carriers in model and human biles. The aim of this study was to explore systematically the effects of various phospholipid head groups on the cholesterol crystallization process in model biles. METHODS: Three different control model biles were prepared using varying proportions of egg lecithin, cholesterol and Na taurocholate. In the test biles, 20% of the egg lecithin was replaced with synthetic phosphatidylserine, phosphatidylethanolamine, phosphatidylglycerol or phosphatidylcholine, keeping the phospholipid acyl chains and other biliary lipids constant in each experiment. RESULTS: Phosphatidylserine and phosphatidylglycerol significantly prolonged the crystal observation time, from 2 days to 10 and 6 days, respectively (p<0.02), while phosphatidylethanolamine had little and phosphatidylcholine no effect. The crystal growth rate was significantly slowed down with 20% phospholipid replacement in the following order: phosphatidylglycerol >phosphatidylserine >phosphatidylethanolamine. The total crystal mass after 14 days, as measured by chemical analysis, was reduced by 59% with phosphatidylserine (p<0.05), and by 73% with phosphatidylglycerol (p<0.05); while phosphatidylethanolamine had little effect. The precipitable cholesterol crystal fractions after 14 days were significantly reduced with phosphatidylserine (54%) and phosphatidylglycerol (37%), but not with phosphatidylethanolamine or phosphatidylcholine. CONCLUSIONS: Variations in the head groups of biliary phospholipids may markedly slow down the cholesterol crystallization process in model biles.

Bile↗

PubMed1998

One-week triple therapy with omeprazole, clarithromycin, and nitroimidazole for Helicobacter pylori infection in children and adolescents.

BACKGROUND: Resolution of Helicobacter pylori infection is important in the management of peptic ulcer disease and reduces peptic ulcer recurrence in both adults and children. Various anti-H pylori treatment regimens have been proposed, reflecting the incomplete clinical success of each. A combination of omeprazole, clarithromycin, and tinidazole, given for 1 week, has been shown to be highly tolerable and effective, achieving a success rate of >90% in the adult population. OBJECTIVE: The aim of this study was to evaluate this short-term regimen in pediatric and adolescent populations. METHODS: The study group consisted of 35 children referred for evaluation of dyspeptic symptoms. They all underwent upper gastrointestinal endoscopy, in which H pylori infection was confirmed by rapid urease test and/or histologic staining. They were given omeprazole (20 mg twice daily), clarithromycin (250 mg twice daily), and tinidazole or metronidazole (500 mg twice daily) for 1 week. The patients were divided into two groups: those who received the first course of anti-H pylori therapy during this study (group 1) and those who had previously received standard metronidazole and bismuth combination therapies that failed to eradicate H pylori (group 2). Therapeutic efficacy was assessed by a 13C-urea breath test performed 4 weeks after completion of treatment. Results. The 35 study patients had a mean age of 15.9 years (range, 10 to 19) and included 19 males and 16 females, of whom 22 were born in Israel and 13 were immigrants from the former USSR. There were 27 patients (77. 1%) in group 1 and 8 patients (22.9%) in group 2. Endoscopic findings were nodular gastritis (14), gastritis (11), gastric ulcer (1), duodenal ulcer (5), and duodenitis (4). H pylori resolution was significantly higher in group 1 patients (24/27, 88.9%) than in group 2 patients (1/8, 12.5%). There was no difference between patients with nodular gastritis and those with nonnodular gastritis, and between Israeli-born patients and patients born in the former USSR. Compliance in both groups was equally good, and no major side effects were recorded. CONCLUSIONS: One-week omeprazole/clarithromycin/tinidazole triple therapy is highly tolerable and effective for treating H pylori in the pediatric age group, but previous treatment failure diminishes the likelihood of success with this regimen.

Adolescent↗

PubMed1997

Metformin enhances clearance of chylomicrons and chylomicron remnants in nondiabetic mildly overweight glucose-intolerant subjects.

OBJECTIVE: To assess the effect of metformin on the metabolism of intestinally derived lipoproteins in nondiabetic individuals who were mildly overweight and glucose intolerant. RESEARCH DESIGN AND METHODS: A total of nine subjects with a BMI > or = 25 kg/m(2) and fasting serum glucose < or = 6.1 mmol/l and who were glucose intolerant were studied. The subjects underwent a vitamin A fat-loading test before and after a 3-month treatment with 850 mg metformin twice a day. The metabolic behavior of the postprandial lipoproteins was compared with that found in a group of 19 healthy normolipidemic individuals who participated in a previous study. RESULTS: Mean total plasma, chylomicron fraction, and nonchylomicron fraction retinyl palmitate (RP) pretreatment levels were 3.4-fold, 3.59-fold, and 3-fold higher, respectively, in the study group than in the normolipidemic group and were reduced by 50, 56, and 32%, respectively, after 3 months of metformin treatment. The decrease of chylomicron levels after treatment was positively correlated to the fasting triglyceride values before treatment (r = 0.73, P = 0.039) and to the serum insulin level at 120 min of standard glucose loading before treatment (r = 0.91, P = 0.002). CONCLUSIONS: Metformin was shown to be beneficial in the clearance of postprandial lipoproteins in nondiabetic individuals who were mildly overweight and glucose intolerant.

Cholesterol↗

PubMed1997

A new method for the rapid measurement of cholesterol crystallization in model biles using a spectrophotometric microplate reader.

Measurements of the cholesterol crystal observation time, and particularly the crystal growth rate in model biles, are important in biliary pathophysiology. The aim of this study was to develop a semi-automated method permitting multiple, simultaneous, and precise measurements of the crystal growth rate in model biles. Incubated model biles were mixed with a high concentration of NaTDC to solubilize non-crystalline turbidity and spectrophotometric measurements were performed. In parallel, samples were observed by light microscopy. The absorbance correlated linearly with the crystal mass and permitted quantitation of the crystal growth rate. Polarized light microscopy was more sensitive than spectrophotometry for determining the initial crystal observation time, while spectrophotometry was more precise and quantitative for measuring the crystal growth rate.

Bile Acids and Salts↗

PubMed1996

The effects of dietary phospholipids enriched with phosphatidylethanolamine on bile and red cell membrane lipids in humans.

The role of phospholipids in biliary cholesterol solubilization and crystallization has only recently begun to be appreciated. Phospholipid vesicles are believed to be the metastable carrier from which cholesterol nucleates. Cholesterol crystallization is influenced by the phospholipid species in bile. Feeding rats and hamsters with diets enriched in phospholipids or their precursors, especially ethanolamine, resulted in reduced cholesterol saturation of bile. Although whole phospholipids are normal dietary constituents, the effects and safety of phospholipid components have not been tested in humans. In the present study, we have evaluated the effects of a dietary phospholipid mixture, enriched with phosphatidylethanolamine, on human bile and red blood cell membrane lipid composition. Five ambulatory volunteers having a chronic indwelling T-tube, with an intact enterohepatic circulation, were investigated. Thirty-six grams of phospholipids (54% phosphatidylethanolamine, 54% linoleyl acyl chains) were added to their daily diet for fourteen days. Biliary nucleation time, cholesterol carriers, as well as plasma, red blood cell membrane, and bile lipid compositions, were monitored. Following phospholipid supplementation, the proportion of linoleyl chains (18:2) in biliary phospholipids increased significantly from 31.1 +/- 1.2 to 37.7 +/- 5.3%, while that of oleyl chains (18:1) decreased from 11.4 +/- 1.6 to 9.6 +/- 1.1%. These changes were accompanied by an increase of linoleate and its metabolite, arachidonate, in red cell membranes. Phospholipid feeding did not cause any side effects, and no significant changes in biliary nucleation time, cholesterol, phospholipid, or bile salt concentrations, or in the distribution of cholesterol within micelles or vesicles. We conclude that phospholipid feeding is safe, and can be effective as a vehicle for lecithin fatty acyl chain modulation of bile and lipid membranes. These findings may provide a basis for a controlled modulation of biliary phospholipids to increase cholesterol solubility in bile.

Adult↗

PubMed1994

Continuous intravenous heparin administration in humans causes a decrease in serum lipolytic activity and accumulation of chylomicrons in circulation.

Heparin is a well-known, widely used anticoagulant drug. In addition to its anticoagulant properties, however, it also has a marked influence on fat metabolism. Postprandial lipoproteins may contribute significantly to the development of coronary heart disease. Therefore, it is important to evaluate the effects of heparin on these lipoproteins. The effect of continuous heparin administration on postprandial lipoprotein metabolism was studied in 11 patients with thromboembolic disease. Results were compared with those in a group of six patients given no heparin. Two vitamin A-fat loading tests were done: the first, 5 days before heparin was started and the second, on the fourth day of continuous heparin drip of 1000 U/h, maintaining PTT levels at twice the baseline. To study the effect of acute heparin, an additional fat loading test was done in five patients on the first day of heparin treatment. Vitamin A, specifically labels intestinally derived lipoproteins with retinyl palmitate (RP). The concentrations of chylomicron (Sf > 1000)- and nonchylomicron (Sf < 100)-retinyl palmitate were measured for 10 h postprandially. Four days of continuous intravenous heparin administration increased the area below the chylomicron RP curve from 11091 +/- 4393 to 17684 +/- 5949 micrograms/l.h (P < 0.003). When measured on the first day of heparin treatment in five patients, the area of the chylomicron fraction was reduced from 16678 +/- 6895 to 10474 +/- 3893 micrograms/l.h (P < 0.05). Postheparin lipoprotein lipase activity was significantly lower on the fourth day of heparin, administration than before treatment: 1.8 +/- 1.1 vs. 4.1 +/- 1.3 mumol/FFA per ml per h, respectively (P < 0.0005). In the six control patients with thromboembolic disease in whom heparin therapy was not indicated, no changes in postprandial lipoprotein levels or in lipolytic activity during hospitalization were found. The study demonstrates that 4 days of heparin administration causes an accumulation of chylomicrons in the circulation, most probably as a result of a marked decrease in serum lipolytic activity.

Adult↗

PubMed1992

Severe defect in clearing postprandial chylomicron remnants in dialysis patients.

Lipid abnormalities have been suggested as a major cause of the accelerated atherosclerosis and the high incidence of coronary heart disease in chronic renal failure patients. In the present work the postprandial lipoprotein metabolism was studied in chronic dialysis patients with or without fasting hypertriglyceridemia using the vitamin A loading test. This method investigates specifically postprandial lipoprotein metabolism. The determination of vitamin A ester level retinyl palmitate (RP) differentiates the circulating plasma chylomicron and chylomicron remnant fractions from the endogenous VLDL and IDL. Subjects with normal renal function with or without fasting hypertriglyceridemia served as control groups. Dialysis patients have significantly higher level of chylomicron remnants for a more prolonged period of time than controls, irrespective of their fasting triglyceride levels. The area below retinyl palmitate chylomicron remnants curve was 26308 +/- 12422 micrograms/liter.hr in the normolipidemic dialysis patients, significantly higher than (6393 +/- 2098 micrograms/liter.hr; P < 0.0001) in the normolipidemic controls. The retinyl palmitate chylomicron remnants curve of the hypertriglyceridemic dialysis patients was 21021 +/- 4560 micrograms/liter.hr, which was higher than 12969 +/- 2215 micrograms/liter.hr (P < 0.0001) in the hypertriglyceridemic controls. Moreover, the hypertriglyceridemic dialysis patients had an additional defect in the lipolysis metabolic step, that is, accumulation of chylomicrons in circulation. These findings show a severe defect in postprandial lipoprotein metabolism in chronic renal failure patients. The prolonged exposure of the vascular wall to high chylomicron remnant concentrations might be an important pathogenetic factor in the accelerated atherosclerosis seen in chronic dialysis patients.

Adult↗

PubMed1992

Octogenarian subjects have low postprandial levels of chylomicron remnants: a possible explanation for protection against atherosclerosis.

Postprandial lipoprotein metabolism may play an important role in the development of atherosclerosis. It is widely believed that in healthy octogenarians, the atherogenic process occurs very slowly. In the present study, postprandial lipoprotein metabolism was examined in 14 octogenarian subjects (mean age, 84 +/- 4.2 years) and 19 younger controls (mean age, 50 +/- 4.8 years) using the vitamin A-fat loading test, in which intestinally derived lipoproteins are specifically labeled with retinyl palmitate (RP). Results indicated that mean peak chylomicron remnant RP levels and the areas below the chylomicron remnant RP curve were significantly lower in the octogenarian group than in the controls (625 +/- 329 vs 1321 +/- 688 micrograms/L and 3740 +/- 1078 vs 6162 +/- 1063 micrograms/L.h, respectively; p < .0001). No differences were found between the two groups in chylomicron RP levels or in lipolytic activity. The study suggests that octogenarians do not exhibit the decrease in chylomicron lipolysis that usually accompanies aging. In addition, these subjects have significantly lower levels of chylomicron remnants in the circulation. Since accumulation of these particles has been implicated in the development of atherogenesis, our findings may indicate a major mechanism of atherosclerosis prevention in healthy octogenarians.

Aged↗