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P Hugh

Publications and source records attributed to P Hugh.

5 recordsLinked to original sources
PubMed1998

Kinetics of triglyceride rich lipoproteins: chylomicrons and very low density lipoproteins.

Lipoprotein dynamics are complex during the postprandial state. A significant rise in chylomicron concentration is associated with increased competition for LPL with VLDL particles. This results in an increased concentration of large VLDL. The concentration of small VLDL is reduced as a result of diminished conversion of large to small VLDL. Such changes, induced in the postprandial state, complicate the application and development of models that describe lipoprotein particle kinetics. The development of models that integrate chylomicron and VLDL particle information, rather than surrogate markers, together with data including other variables will provide insight into the complexity of lipoprotein metabolism in the postprandial state.

Animals↗
PubMed1997

A familial combined hyperlipidemic kindred with impaired apolipoprotein B catabolism. Kinetics of apolipoprotein B during placebo and pravastatin therapy.

Familial combined hyperlipidemia (FCHL) is a heterogeneous disorder characterized by multiple lipoprotein phenotypes, a high risk for coronary heart disease, and predominance among the LDL fraction of smaller and denser particles. We report on an FCHL kindred (the M-kindred) in which decreased VLDL- and LDL-apoB elimination rates rather than enhanced production rates were the main kinetic abnormalities. Lipoprotein levels and metabolic parameters of all apoB-containing lipoproteins (including light and dense LDLs) were determined during placebo and pravastatin treatment periods. ApoB metabolism was studied by endogenous labeling with stable isotopes and a multicompartmental model. Five members of the M-kindred participated. The study was doubly blinded, randomized, and placebo controlled. Treatment periods of 6 weeks were separated by 2-week washout periods. All subjects had high apoB levels, 2 had a mixed lipemia, 1 had hypercholesterolemia, and 2 had hypertriglyceridemia. Familial dysbetalipoproteinemia, hypercholesterolemia, and defective apoB-100 were excluded by genetic, testing. Kinetic parameters were remarkably similar in the five study subjects during the placebo period, despite their diverse plasma lipid profiles. Compared with nine normolipidemic control subjects, low VLDL-apoB fractional catabolic rates (FCRs) (3.6 +/- .1 versus 9.3 +/- 2.9 pools per day) and low LDL-apoB FCRs (0.19 +/- 0.05 versus 0.41 +/- 0.13 pool per day) were observed in every case. The majority of the LDL particles were identified in the denser fraction (d = 1.036 to 1.063 g/mL). A clear precursor-product relationship was observed from VLDL to IDL to light LDL to dense LDL, ie, there was no "metabolic channeling." Light LDL had significantly higher FCR than dense LDL (0.82 +/- 0.21 versus 0.22 +/- 0.08 pool per day). VLDL-apoB production rates were normal (19.7 +/- 6.0 versus 21.6 +/- 6.1 mg/kg per day for control subjects). In contrast, in two subjects drawn from two other FCHL kindreds (the C- and K-kindreds), VLDL-apoB production rates were increased (35.6 and 32.1 mg/kg per day, respectively). In these two, more "typical" FCHL subjects, FCRs of LDL-apoB were near normal (0.351 and 0.311 pool per day, respectively). Pravastatin (20 mg/d) resulted in significantly lower plasma cholesterol (265 +/- 30 to 218 +/- 16 mg/dL, P < .01), LDL cholesterol (186 +/- 31 to 145 +/- 15 mg/dL, P < .03), and apoB levels (168 +/- 14 to 125 +/- 16 mg/dL, P < .01) in the five FCHL subjects of the M-kindred. No changes were observed in plasma HDL cholesterol, apoA-I, or lipoprotein(a). Pravastatin significantly increased the LDL-apoB FCR (from 0.19 +/- 0.05 to 0.34 +/- 0.04 pool per day). The FCRs of both LDL subclasses increased with treatment. No pravastatin-induced changes were seen in apoB production rates.

Adolescent↗
PubMed1996

Design and analysis of lipid tracer kinetic studies.

A fundamental problem in lipid metabolism is designing experiments to quantitate the kinetics of the plasma lipids and lipoproteins in the body. Tracers have been used extensively. In this review, we will combine our knowledge of the theory and application of tracer kinetic studies to discuss current state of the art methodologies for lipid metabolism. We will review the use of stable and radioactive isotopes pointing out the importance of the measurement variables, and the theory and application of noncompartmental and compartmental models to interpret the data.

Humans↗
PubMed1991

Determination of kinetic parameters of apolipoprotein B metabolism using amino acids labeled with stable isotopes.

The use of amino acids labeled with stable isotopes represents a relatively new approach for determining kinetic parameters of apolipoprotein metabolism; thus, several aspects of experimental protocols need to be defined. The aims of the present study were to determine whether a) different amino acid tracers or b) different methods of tracer administration affected apolipoprotein (apo) B kinetic parameters obtained by multicompartmental modeling, and c) to compare very low density lipoprotein (VLDL)-apoB metabolic parameters determined by multicompartmental modeling with those estimated by linear regression or by monoexponential analysis. [1-13C]leucine and [15N]glycine were given either as bolus injections or as primed constant infusions. A bolus of one amino acid was administered simultaneously with a primed constant infusion (8 h) of the other amino acid into four healthy normolipidemic subjects (age 23.0 +/- 1.4 yr; BMI 20.9 +/- 0.9 kg.m-2). VLDL-, intermediate density lipoprotein (IDL)-, and low density lipoprotein (LDL)-apoB enrichments were followed over 110 h. For subsequent analysis these values were converted to tracer/tracee ratios. Using the multicompartmental model, the fractional catabolic rate (FCR) for VLDL-apoB was estimated to be 0.36 +/- 0.09 h-1 after the administration of the tracer as a primed constant infusion and 0.35 +/- 0.07 h-1 when the tracer was administered as a bolus. The values for VLDL-apoB production were 14.6 +/- 6.5 mg.kg-1.d-1 and 14.1 +/- 5.4 mg.kg-1.d-1, respectively. The corresponding values for LDL-apoB were 0.027 +/- 0.016 h-1 (0.026 +/- 0.018 h-1) for the FCR and 10.5 +/- 3.7 mg.kg-1.d-1 (10.4 +/- 3.8 mg.kg-1.d-1) for the production following administration of the tracer as a primed constant infusion and a bolus, respectively. Approximately 47% of VLDL-apoB ultimately reached the LDL fraction via the VLDL-IDL-LDL pathway. Thirty-five percent of LDL-apoB did not originate from this cascade pathway, but was shunted from a rapidly turning over VLDL compartment directly into the LDL fraction. While there was some variation between individuals, VLDL-apoB and LDL-apoB parameters derived from the bolus and the primed constant infusions showed no significant differences and were closely correlated. Metabolic parameters were also independent of the two amino acids tested. Although values for FCRs of VLDL-apoB obtained from linear regression (0.36 +/- 0.19 h-1) or monoexponential analysis (0.50 +/- 0.36 h-1) did not differ significantly from those obtained by the multicompartmental model, there was considerable variation and no significant correlation in a given individual.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗