Rebound Curve Following LDL-Apheresis Reflects Catabolic Rate of Plasma Cholesterol And The Synthetic Rate of Lp(A)

1996 ◽  
pp. 591-597 ◽  
Author(s):  
Mariko Harada-Shiba ◽  
Taku Yamamura ◽  
Yasushi Toyota ◽  
Motoo Tsushima ◽  
Shunichi Kojima ◽  
...  
Keyword(s):  
Plasma Cholesterol ◽  
Ldl Apheresis ◽  
Synthetic Rate ◽  
Catabolic Rate

α2-Antiplasmin: Functional Characterization and Metabolism in a Heterozygote Deficient Patient

1986 ◽  
Vol 55 (03) ◽  
pp. 375-378 ◽  
Author(s):  
E A R Knot ◽  
J W ten Cate ◽  
R J Lamping ◽  
Liem Kian Gie
Keyword(s):  
Half Life ◽  
Functional Characterization ◽  
Bleeding Tendency ◽  
Normal Range ◽  
Crossed Immunoelectrophoresis ◽  
Synthetic Rate ◽  
Catabolic Rate ◽  
Deficient Patient ◽  
Antigen Activity ◽  
Bleeding History

SummaryAn 81-year-old male with a mild life-long bleeding history and an α2-antiplasmin (α2-AP) plasma level of 55% biological activity and 41% antigen activity (normal range 80-140%) was studied. The ratio of plasminogen binding (PB): non-plasminogen binding (NPB) α2-AP assayed by modified crossed immunoelectrophoresis (CIE) was 7.3/2.7 (controls 6.3 ± 0.49 SD/3.7 ± 0.49 SD). The patient’s α2-AP showed decreased affinity for fibrin, i. e. 8.3% versus 32.4% of normal control α2-AP associated with fibrin during clotting of plasma. A metabolic study performed with human purified 125I-α2-AP(PB/NPB 7.7/2.3) showed a plasma radioactivity disappearance half-life of 72.9 h (n 60.1 ± 5.3 h) with a normal fractional catabolic rate and a reduced absolute catabolic (synthetic) rate of 0.70 mg/kg/day (n 2.10 ± 0.60 mg/kg/day). The exchange between the central and third compartment was increased. The increased α2-AP PB form and the increased plasma radioactivity disappearance half-life are suggestive of a slower conversion of the PB form into the NPB form and/or slower degradation of the PB form. The bleeding tendency in this patient could be explained by decreased synthesis of α2-AP and decreased binding to fibrin.

scholarly journals Regulation of low-density-lipoprotein metabolism in the rat

1986 ◽  
Vol 234 (2) ◽  
pp. 493-496 ◽  
Author(s):  
S Bhattacharya ◽  
S Balasubramaniam ◽  
L A Simons
Keyword(s):  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
Hormonal Control ◽  
Low Density ◽  
Experimental Conditions ◽  
Synthetic Rate ◽  
Catabolic Rate ◽  
Intermediate Density

The mechanism of regulation of plasma low-density-lipoprotein (LDL) metabolism in the rat was studied under a number of experimental conditions. LDL clearance and uptake in the liver was measured after intravenous pulse injection of [14C]sucrose-labelled LDL alone or in combination with reductively methylated [3H]sucrose-labelled LDL. Hyperthyroid rats showed a significant increase in fractional catabolic rate (FCR) and the proportion of LDL degraded in the liver, whereas the synthetic rate of LDL increased by 50%. Receptor-mediated clearance increased 2-fold. Hypothyroid rats showed a significant increase in LDL concentration. The FCR and proportion of LDL degraded in the liver were decreased significantly. Receptor-mediated clearance was also reduced. Cholesterol feeding increased chylomicron, very-low-density-and intermediate-density-lipoprotein cholesterol concentrations, but there was no change in the LDL concentration, FCR or the synthetic rate of LDL. Cholestyramine feeding did not induce changes in the kinetic parameters. These results indicate that, in the rat, the hepatic LDL-receptor pathway is under hormonal control, whereas cholesterol and cholestyramine feeding have no demonstrated effect on LDL metabolism.

Abstract 329: Mechanism by Which Anacetrapib Lowers Plasma Lipoprotein (a) Concentration

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Tiffany A Thomas ◽  
Haihong Zhou ◽  
Thomas Roddy ◽  
Stephen Previs ◽  
Michael Lassman ◽  
...  
Keyword(s):  
Plasma Lipoprotein ◽  
Entire Group ◽  
Fixed Sequence ◽  
Lipoprotein A ◽  
Synthetic Rate ◽  
Period 2 ◽  
Catabolic Rate ◽  
Fractional Synthetic Rate ◽  
Cetp Inhibitor ◽  
Sequence Study

Objective: Anacetrapib, a CETP inhibitor, was previously shown to decrease plasma lipoprotein (a) [Lp(a)] levels by 35-40% in subjects also taking a statin. Thus, anacetrapib is an efficacious Lp(a)-lowering agent. The goal of this study was to define the mechanism by which anacetrapib lowers plasma Lp(a) levels. Methods: 39 moderately hyperlipidemic volunteers were enrolled in a fixed-sequence study, in which 75% were on atorvastatin 20mg/day, plus placebo for four weeks (period 1), and then atorvastatin plus anacetrapib (100 mg/day) for 8 weeks (period 2). The other 25% of the subjects received double placebo for four weeks, and then placebo plus anacetrapib for 8 weeks. Turnover studies using D3-leucine were performed at the end of each period. The present analysis utilized samples from a subset of subjects (n=12) who had plasma Lp(a) levels greater than 10 nM at the end of period 1 and had a greater than 10% reduction in Lp(a) by the end of period 2. The fractional synthetic rate (FSR:equal to fractional catabolic rate at steady state) of mature Lp(a), isolated from a D:1.019-1.21 g/ml density interval, was determined from the enrichment of a leucine-containing peptide specific to apo(a). The production rate (PR) of mature Lp(a) was calculated from the FSR and the Lp(a) pool size. To date, we have calculated the FSR and PR in 4 participants. Results: Baseline Lp(a) mean levels were 45.7 ± 6.3nM in the entire group and 56.5 ± 33.6nM in the 12 qualifying subjects. Anacetrapib lowered Lp(a) by 43 ± 22% in the 12 subjects and 21 ±12% in the 4 subjects with turnover data. In these 4 subjects, the reduction in mature Lp(a) was associated with a 24% reduction in FSR and a 41% reduction in PR. Lp(a) kinetics analyses of the remaining 8 subjects are in progress. Conclusion: These preliminary results suggest that anacetrapib decreases Lp(a) levels by significantly decreasing the production of mature Lp(a). Additional analyses are planned to determine if the reduced production of Lp(a) results from decreased entry of Lp(a) into plasma or reduced conversion of a precursor form to the mature Lp(a).

Experimental studies of the fibrinogen response to hemorrhage

1979 ◽  
Vol 237 (4) ◽  
pp. H504-H513
Author(s):  
E. B. Reeve ◽  
A. Stephens ◽  
T. H. Carlson
Keyword(s):  
Total Protein ◽  
Transfer Rate ◽  
Experimental Studies ◽  
Plasma Fibrinogen ◽  
Simulation Methods ◽  
Red Cell ◽  
Total Plasma ◽  
Synthetic Rate ◽  
Catabolic Rate ◽  
Synthetic Work

Rabbits were bled 20 ml/kg body wt over approximately 1 h, and the changes in hematocrit, plasma total protein, and fibrinogen concentrations, red cell and plasma volumes, and masses of total protein and fibrinogen in the plasma during and for 4 days after the hemorrhage were monitored. Ten percent of plasma fibrinogen was transferred from the interstitial fluids during the hemorrhage, and total plasma fibrinogen was raised to 140% of initial levels by 1 day later. 131I-labeled fibrinogen was given intravenously 1 day before a 20 ml/kg hemorrhage, and simulation methods described in the APPENDIX were used to define changes in the posthemorrhage fractional rates: transcapillary transfer rate (j1), lymphatic return rate (j2), and catabolic rate of fibrinogen (j3): j1 was unchanged but j2 increased and j3 briefly declined. In the day after hemorrhage fibrinogen synthetic rate increased approximately threefold to restore plasma fibrinogen concentrations to initial levels, but then returned to normal or subnormal levels. The alterations in j2 and j3 save about 20% of the synthetic work that would otherwise be required to restore plasma fibrinogen levels to normal.

Hormonal effects on metabolism and distribution of plasma albumin in the dog

1964 ◽  
Vol 206 (6) ◽  
pp. 1229-1236 ◽  
Author(s):  
Y. Takeda
Keyword(s):  
Growth Hormone ◽  
Body Weight ◽  
Time Distribution ◽  
Experimental Period ◽  
Passage Time ◽  
Plasma Albumin ◽  
Control Value ◽  
Synthetic Rate ◽  
Hormone Injection ◽  
Catabolic Rate

The effects of growth hormone, cortisone, and thyroxine on the metabolism and distribution of plasma albumin were studied, using albumin-I131 as a tracer. Growth hormone did not significantly change the synthetic and catabolic rates of albumin in the steady state reached 7 days after the start of the hormone injection, but the increased body weight and total exchangeable albumin in the first 7 days indicate either increased synthetic or decreased catabolic rate of albumin during that period. Cortisone immediately increased the catabolic rate of plasma albumin to a level 28% above the control value, and this level was maintained during the entire experimental period, but the synthetic rate slowly rose to equal the raised catabolic rate by about the 7th day. Thyroxine showed effects similar to those observed with cortisone. It was also shown that all the hormones stimulated the rate of transcapillary transport of albumin and significantly altered the passage time distribution of albumin flux through the interstitial fluids.

Use of deuterated water for measurement of short-term cholesterol synthesis in humans

1990 ◽  
Vol 68 (7) ◽  
pp. 955-959 ◽  
Author(s):  
Peter J. H. Jones
Keyword(s):  
Cholesterol Synthesis ◽  
De Novo ◽  
Plasma Cholesterol ◽  
Isotope Ratio Mass Spectrometry ◽  
Deuterated Water ◽  
Short Term ◽  
Synthetic Rate ◽  
Ε4 Allele ◽  
Deuterium Enrichment ◽  
Free Plasma

Previous methods for measurement of cholesterol synthesis de novo in humans have either required extended measurement periods or been indirect. Recently, a technique based on the rate of incorporation of deuterium from D2O into the plasma cholesterol pool has been developed. Following oral ingestion of D2O, deuterium enrichment over time in free plasma cholesterol after combustion and reduction was determined using isotope ratio mass spectrometry. This methodology enabled direct measurement of plasma cholesterol synthesis over intervals as short as 4 h. The technique has been used to demonstrate changes in synthetic rate in response to feeding conditions and genetic influences. Fasting over 36 h resulted in markedly reduced deuterium uptake into cholesterol in healthy males. Diurnal variations in synthetic rate have also been identified, with elevated synthesis observed during nocturnal periods in both fed and fasted subjects. In addition, the influence of apolipoprotein E phenotype on cholesterol synthesis has been shown using this technique. Individuals carrying the apoprotein ε2 allele demonstrated lower synthesis compared with those possessing the ε4 allele. Thus, the deuterium incorporation technique for measuring cholesterol synthesis demonstrates potential as a valuable stable isotope method for human nutrition studies.Key words: cholesterol synthesis, human, deuterium, methodology.

Alterations in the HDL system after rapid plasma cholesterol reduction by LDL-apheresis

Metabolism ◽  
1988 ◽  
Vol 37 (8) ◽  
pp. 752-757 ◽  
Author(s):  
Guido Franceschini ◽  
Paola Apebe ◽  
Laura Calabresi ◽  
Ghil Busnach ◽  
Luigi Minetti ◽  
...  
Keyword(s):  
Plasma Cholesterol ◽  
Cholesterol Reduction ◽  
Ldl Apheresis

scholarly journals Effect of Low-Density Lipoprotein Apheresis on Kinetics of Apolipoprotein B in Heterozygous Familial Hypercholesterolemia1

2001 ◽  
Vol 86 (4) ◽  
pp. 1679-1686
Author(s):  
Cyrille Maugeais ◽  
Khadija Ouguerram ◽  
Regis Frénais ◽  
Pascale Maugère ◽  
Bernard Charbonnel ◽  
...  
Keyword(s):  
Apolipoprotein B ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
Low Density ◽  
Fractional Catabolic Rate ◽  
Ldl Apheresis ◽  
Catabolic Rate ◽  
High Level

The acute reduction of low-density lipoprotein (LDL) cholesterol obtained by LDL-apheresis allows the role of the high level of circulating LDL on lipoprotein metabolism in heterozygous familial hypercholesterolemia (heterozygous FH) to be addressed. We studied apolipoprotein B (apoB) kinetics in five heterozygous FH patients before and the day after an apheresis treatment using endogenous labeling with [2H3]leucine. Compared with younger control subjects, heterozygous FH patients before apheresis showed a significant decrease in the fractional catabolic rate of LDL (0.24 ± 0.08 vs. 0.65 ± 0.22 day−1; P < 0.01), and LDL production was increased in heterozygous FH patients (18.9 ± 7.0 vs. 9.9 ± 4.2 mg/kg·day; P< 0.05). The modeling of postapheresis apoB kinetics was performed using a nonsteady state condition, taking into account the changing pool size of very low density lipoprotein (VLDL), intermediate density lipoprotein, and LDL apoB. The postapheresis kinetic parameters did not show statistical differences compared with preapheresis parameters in heterozygous FH patients; however, a trend for increases in fractional catabolic rate of LDL (0.24 ± 0.08 vs. 0.35± 0.09 day−1; P = 0.067) and the production of VLDL (13.7 ± 8.3 vs. 21.9 ± 1.6 mg/kg·day; P = 0.076) was observed. These results suggested that the marked decrease in plasma LDL obtained a short time after LDL-apheresis is able to stimulate LDL receptor activity and VLDL production in heterozygous FH.

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