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Biomedical subjects

P Samuel

Publications and source records attributed to P Samuel.

At least 91 records · Page 5Linked to original sources
PubMed1975

Measurement of cholesterol synthesis in man by isotope kinetics of squalene.

A method for measuring the rate of total daily cholesterol synthesis in man has been developed through isotope kinetic studies of squalene biosynthesis after intravenous administration of [14C]mevalonic acid. Plasma squalene becomes rapidly labeled, reaching maximal specific activity approximately 100 min after mevalonate administration and then decays exponentially to reach undetectable levels in 12 hr. The rate of daily squalene synthesis equals the percent dose of mevalonate converted to cholesterol divided by the area under the specific activity curve of squalene; the fraction of the dose of mevalonate converted to cholesterol is calculated by the simultaneous injection of [3H]- and [14C] cholesterol in plasma. The premise that squalene and cholesterol synthetic rates are equivalent was tested. In seven patients it was found that the mean daily cholesterol synthesis rates estimated simultaneously by sterol balance and by sqyalene kinetic methods agreed within 8%. In addition, fractional conversions of mevalonic acid to cholesterol were highly correlated with cholesterol synthesis rates. Maximum estimates of the pool sizes and half-lives of metabolically "active" squalene also were obtained. This measurement of daily cholesterol synthesis by squalene kinetics minimizes patient inconvenience, is suitable for outpatient studies, and yields results in 4 weeks or less. Because of the rapidity of the rate of squalene synthesis, the results obtained reflect cholesterol synthesis over a period of less than 10 hr and are therefore uniquely applicable to unsteady state situations.

Adult↗
PubMed1975

Effects of neomycin on absorption, synthesis, and/or flux of cholesterol in man.

The mode of action of the hypocholesteremic drug neomycin (2 g/day) was studied in four patients. All showed a significant reduction in plasma cholesterol concentrations (mean 25 percent, range 18-31 percent), and in one of three patients with hyperglyceridemia there was a decrease of plasma triglycerides of 26 percent. Cholesterol absorption was measured in three of four patients: there was a marked decrease. Sterol balance studies in four patients showed an unabating increase in fecal neutral steroid excretion (mean increase 345 mg/day, range 323-361) for 3-5 wk after plasma cholesterol levels had reached a new and lower plateau. Fecal acidic steroid excretion increased temporarily in two patients, with a sustained increase of 93 mg/day in only one. Daily stool weights increased significantly in three of four patients, though none had steatorrhea; there was a significant reduction in excretion of secondary bile acids; neutral sterol degradation rates were not affected by the drug. Slopes of plasma cholesterol-specific activity time curves did not change. These results fail to support the suggestion that neomycin acts as a bile acid precipitant. The finding of increased fecal neutral steroid excretion is consistent with decreased cholesterol absorption, but also with increased cholesterol absorption, but also with increased cholesterol synthesis (secondary to release of negative feedback control), with increased flux of cholesterol from tissues, or with a combination of all three actions.

Aged↗
PubMed1973

Improved estimation of body masses and turnover of cholesterol by computerized input--output analysis.

In 23 patients, the decay curves of serum cholesterol specific activity after a single intravenous dose of radioactive cholesterol were measured for 16-66 wk and were subjected to computerized input-output analysis. Of 17 patients with decay curves followed for longer than 50 wk, a three-exponential curve fit was better in 12, and a two-exponential curve fit in 5, according to computerized F tests. Of six patients with decay curves followed for less than 50 wk, a two-exponential curve fit was better in five and a three-exponential curve fit in one. In the 13 patients who exhibited three-exponential curve fits, the third exponential appeared after 13-43 wk of observation (average, 25 wk). In 12 patients of this group who were followed for 50 wk or more, turnover rates and exchangeable masses of cholesterol were measured at maximum lengths of the curves (50-66 wk), and these parameters were then compared with measurements made with curves successively shortened down to 10-12 wk. The average differences between analyses of the minimum vs. the maximum lengths of the curves were: It (input rate: absorbed dietary plus biosynthesized cholesterol), 14% larger (1.24 vs. 1.09 g/day); M(a) (rapidly exchangeable mass of cholesterol), no change (34 vs. 33 g); M (total exchangeable mass), 26% smaller (67 vs. 91 g); M - M(a) (remaining exchangeable mass), 39% smaller (40 vs. 65 g). Significant differences in It, M, and M - M(a) (minimum vs. maximum curve lengths) were found in both normolipidemic and hypercholesterolemic patients, and the differences were of similar magnitude in the two groups. Since only 12 of 17 patients followed for 50 wk or longer demonstrated three-exponential curve fits, various means were sought by which it might be predicted at the outset whether a given patient must be studied for so long a time; none was found. However, in the group with two exponentials the value of M(a) was significantly larger than those with three-exponential curve fits, and this difference was apparent at as early as 10-12 wk.

Adolescent↗
PubMed1972

Long-term kinetics of serum and xanthoma cholesterol radioactivity in patients with hypercholesterolemia.

In four patients with hypercholesterolemia (type II hyperlipoproteinemia) and xanthomatosis the decay of serum cholesterol specific activity was followed for 53-63 wk after pulse labeling. Specific activity of biopsied xanthoma cholesterol was measured four times in the course of the study. The xanthoma specific activity curve crossed and thereafter remained above the serum specific activity curve. The average ratio of xanthoma to serum specific activity was 4.7 at the end of the study. The final half-time of the xanthoma decay curves was significantly greater (average: 200 days) than the slowest half-time of serum specific activity decay (average: 93 days). The data were analyzed by input-output analysis and yielded the following results. The average value for the total input rate of body cholesterol (I(T)) (sum of dietary and biosynthesized cholesterol) was 1.29 g/day. The average size of the rapidly miscible pool of cholesterol (M(a)) was 55.7 g. and of the total exchangeable body mass of cholesterol (M) 116.5 g. The average value of M - M(a) (remaining exchangeable mass of cholesterol) was 60.8 g. The derived values for exchangeable masses of cholesterol, in the present patients with marked hypercholesterolemia, were significantly larger than in a group of patients with normal serum lipids in previous studies. One of the four patients died of a sudden acute myocardial infarction 53 wk after pulse labeling. Specific activity of aortic wall and atheroma cholesterol was 3.12 times that of serum. The ratio was close to 2 for adipose tissue and spleen, and was slightly above 1 or was close to unity in most other organs studied, with the exception of brain which showed a ratio of 0.19.

Adolescent↗
PubMed1970

Long-term decay of serum cholesterol radioactivity: body cholesterol metabolism in normals and in patients with hyperlipoproteinemia and atherosclerosis.

After the intravenous injection of labeled cholesterol, the decay of specific radioactivity of total serum cholesterol was studied in 12 patients for 15-63 wk (average, 45 wk). In some, but not all of the patients studied, the slow slope of the decay curves suggested a deviation from monoexponential behavior, and the data of the slow period of the decay of specific activity were curve fitted by two exponentials. Six patients had serum lipid values regarded as normal and six had hyperlipoproteinemia. The data were analyzed by input-output analysis and yielded the following results. Values for the input rate of cholesterol (I(T)) (the sum of dietary and biosynthesized cholesterol) showed no difference between the normals and patients with hypercholesterolemia. The size of the rapidly miscible pool of cholesterol (M(a)) was significantly higher in the group of hypercholesterolemic patients partly due to increased serum cholesterol levels. The size of the total exchangeable body mass of cholesterol (M) was higher by an average of 49 g in the patients with hypercholesterolemia as compared to normals. The remaining exchangeable mass of cholesterol (M - M(a)) of the hypercholesterolemic subjects was higher by an average of 29 g as compared to normals. These differences were statistically significant.

Adult↗