Pre-beta Fraction Research Articles

Динаміка деяких показників ліпідного обміну у вівцематок сходу України

Динаміка деяких показників ліпідного обміну у вівцематок сходу України

Recombinant High-Density Lipoprotein Formulations

High-density lipoprotein cholesterol (HDL-C) has emerged as a biomarker of residual cardiovascular disease (CVD) risk in high-risk patients treated with low-density lipoprotein cholesterol (LDL-C)-lowering therapies inclusive of inhibitors of 3-hydroxy-3-methyl-glutaryl-CoA reductase. The evidence for increasing low levels of HDL-C is sparse, and the available data are confounded by metabolic interactions between elevated very low-density lipoprotein (VLDL) and LDL particle concentrations. Despite these limitations, there has been widespread interest in novel strategies that target HDL. One such path has been the development of recombinant HDL formulations that mimic the pre-beta fraction of native HDL, which is the main HDL subclass that mediates cholesterol efflux from lipid-laden macrophages. Various recombinant HDL formulations (apolipoprotein A-1 [apoA-1]-bound phospholipid disks or delipidated HDL particles, mutant apoA-1 proteins, and apoA-1 mimetic peptides) have been investigated in animal studies and some human trials. However, these HDL-modifying therapies require evaluation in clinical trials of atherosclerosis and CVD events. This review presents our current knowledge on novel recombinant therapies, and their future prospects to mitigate atherosclerotic CVD events.

Palmar spiny keratoderma associated with type IV hyperlipoproteinemia

We report the case of a 35-year-old man with acquired palmar spiny keratoderma (SK) in association with type IV hyperlipoproteinemia. Cutaneous lesions appeared 11 years before with no history of any previous skin conditions, topical medication or systemic treatment with Vitamin A-derived drugs, x-irradiation, arsenic poisoning or prolonged sun exposure. Family aggregation for SK or other disorders of keratinization was ruled out. Blood chemistries demonstrated hypertriglyceridemia (422 mg/dl) and elevation in plasma concentration of the pre-beta fraction (VLDL) of lipoproteins pattern compatible with a type IV hyperlipoproteinemia. Family aggregation for this metabolic defect was then confirmed. The histologic hallmark of the 'spine' lesion was a compact column of hyperparakeratotic cells (columnar hyperparakeratosis) continuous with a hypogranular layer, without further evidence of dyskeratotic or vacuolated keratinocytes and inflammatory cells in the corresponding dermis. SK represents a well-definite entity which fulfills precise clinico-histologic criteria. However, three main questions are related to SK: differential diagnosis with porokeratosis on histologic examination (columnar hyperparakeratosis or hyperorthokeratosis alone in SK vs. cornoid lamella accompanied by remarkable dermoepidermal changes in porokeratosis); classificative scheme (proper nomenclature to avoid misleading and confounding names); and nosological arrangement (probably two subsets exist: hereditary or benign; and acquired, or idiopathic, which may be paraneoplastic in about 50% of the patients). To the best of our knowledge this is the first case reporting the association between SK and a metabolic impairment although the real connections linking these conditions are still unclear.

Hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration (HARP syndrome)

We describe the clinical and laboratory studies of an 11-year-old girl with prominent orofacial dyskinesia, dystonia, and progressive dementia. Investigations revealed hypoprebetalipoproteinemia, acanthocytosis, atypical retinitis pigmentosa, and evidence of iron deposition in the pallidal nuclei. Electroneuromyography and skin and sural nerve biopsies were normal. The "eye-of-the-tiger" sign, used to describe the pallidal nuclei in Hallervorden-Spatz syndrome, was present on T2-weighted MRIs (GE Signa, 1.5 T). Phase-contrast microscopy of whole blood showed 80 to 90% acanthocytes whose morphology was confirmed by electron microscopy. High-resolution lipoprotein electrophoresis demonstrated an absence of the pre-beta fraction. This case differs phenotypically from the previous reports of Hallervorden-Spatz disease with acanthocytosis by the presence of prominent orofacial dyskinesia and abnormal serum lipoproteins.

Exercise‐Induced Transient Hyperlipidemia in the Racehorse

Effects of graded intensity exercise on plasma lipids was studied in Standardbred and Finnishbred Trotters. The rate of lipolysis indicated by the elevated plasma concentrations of glycerol increased parallel with the intensity of the trot in the Standardbreds, but not as clearly in the Finnishbred trotters. During the exercise plasma triglyceride concentration increased significantly and the increase correlated with the intensity of the exercise as well as the activity of lipolysis. Together with the increase in plasma triglycerides, there was a parallel increase in the pre-beta fraction of lipoproteins which suggests that the hepatic synthesis of triglycerides was increased. It was calculated that about one third of the nonesterified fatty acids released in lipolysis during the high-intensity exercise is oxidized and the remainder is used for resynthesis of triglycerides. Since there were interstrain differences in the concentrations of triglycerides and glycerol after the high-intensity exercise it is suggested that the differences may be of some value in the estimation of recovery after submaximal exercise.

Lipoprotein electrophoresis in fat embolism: a preliminary report

Serum lipoprotein electrophoresis and other laboratory tests were made on 14 injured patients over 10 days. Reduction in the pre-beta fraction to an average of 6 per cent, with an elevation of the alpha lipoprotein fraction to an average of 41 per cent, were recorded. The patients without complications regained their normal lipoprotein pattern within 48 hours, while in the two cases who developed fat embolism, the deranged pattern lasted for up to 10 days. The clinical diagnosis of fat embolism is based on signs that appear generally within 3 days following injury. As prognosis depends on early diagnosis, in order to start treatment before full blown clinical signs are present, there is the need for a laboratory test which gives early results and is reliable and easy to perform. This study shows an apparently distinct pattern of the serum lipoproteins which may provide us with a warning about which patients are at risk of developing fat embolism.

Use of Sodium Polyanetholesulfonate-CaCl 2 for Removal of Serum Nonspecific Inhibitors of Rubella Hemagglutination: Comparison with Other Polyanion-Divalent Cation Combinations

By using trypsin-treated human type O cells as indicators, we compared the abilities of four polyanion-divalent cation combinations (heparin-MnCl(2); high-and low-molecular-weight dextran sulfate-CaCl(2); and sodium polyanetholesulfonate [SPS]-CaCl(2)) for removal of serum non-immunoglobulin (lipoprotein) inhibitors of rubella hemagglutination. The combination of SPS-CaCl(2) was found to be the most effective, precipitating completely the pre-beta and beta-lipoproteins and reducing the alpha-lipoprotein levels by more than 50%. Hemagglutination patterns after this treatment were clear and stable, and, when normal sera were tested, hemagglutination-inhibition (HI) titers were comparable to those obtained after standard heparin-MnCl(2) treatment. High-molecular-weight dextran sulfate-CaCl(2) removed serum lipoproteins almost as effectively as SPS-CaCl(2). However, problems of nonspecific agglutination and the heavy hemagglutination patterns resulting made this combination unacceptable for routine purposes. Neither low-molecular-weight dextran sulfate-CaCl(2) nor heparin-MnCl(2) removed the pre-beta lipoproteins completely, and occasionally traces of beta-lipoprotein also remained after treatment. The presence of pre-beta lipoproteins in normal sera after treatment may be of no consequence in the HI test since we have found that the very-low-density lipoprotein fractions obtained by ultracentrifugal methods from normal sera (those corresponding to the pre-beta fractions obtained by electrophoresis) had no HI activity. However, very-low-density lipoprotein fractions from all hyperlipemic sera tested had HI activity (titers ranging from 1:16 to 1:1,024) which, in the majority of cases, was not eliminated after heparin-MnCl(2) treatment. In every case, treatment with SPS-CaCl(2) removed this nonspecific activity completely. Since hyperlipemic sera may occasionally be encountered in routine rubella HI antibody testing, we recommend the use of SPS-CaCl(2) rather than heparin-MnCl(2) for pretreatment of sera.

LIPID CHANGES ASSOCIATED WITH PSYCHOSOCIAL DWARFISM (PSD)

Turbidity of fasting serum and a distinctive pattern of changing blood lipids was observed during the first week of hospitalization in 14 children aged 1.9-14.3 yrs with PSD. All demonstrated remarkable catch-up growth with changed environment. On day 1 (morning of admission) mean (X) fasting triglyceride (TG) was 69% and cholesterol (C) 156 mg%. Fasting sera in 11/12 were turbid without clearing after 48 hrs. During the first 4 days, serial observations in 10/11 children showed dramatic rise in TC (36-594%) with decrease to normal by day 6-8. Serum C gradually rose in 6/14 by day 6-9 (29-52%). During this time serum turbidity cleared. Paper lipoprotein electrophoresis of 10 hr fasting serum was normal except for a light chyle spectrum in 7/13 and an increased beta band in 1/13. An increase in prebeta fraction occurred on day 2-4 in 10/12. Recurrence of turbidity occurred after 15/21 parent visits, clearing again with parent-child separation. By contrast, 5 children with growth failure and protein-calorie malnutrition, 1.2-3.9 yrs, 24 children with hypopituitarism, 1.2-17.1 yrs (X TC 66 mg%; x C 182 mg%) and 16 children with other endocrine disorders undergoing similar hospital evaluations (X C 163 mg%) had clear fasting sera on day 1. No change in serum appearance, TG or C was seen in 8/8 of these followed serially during days 1-4. The presence of serum turbidity may provide a clue to diagnosis in psychologically induced growth retardation. The mechanism of this phenomenon is as yet unexplained.

PLASMA LIPIDS AND LIPOPROTEINS IN PROTEIN‐CALORIE MALNUTRITION

Plasma triglycerides, phospholipids and total cholesterol estimations and lipoprotein electrophoresis on agarose gel were done in control, Kwashiorkor, and marasmic kwashiorkor children. The beta lipoprotein percentage in both conditions is reduced to a statistically significant extent, whereas there is a statistically significant increase in plasma triglycerides in both conditions. Pre-beta fraction was present in all cases, and even increased in marasmic kwashiorkor, which is found to be significant. The results do not support the hypothesis that fatty liver in kwashiorkor is due to impaired release of triglycerides from liver.

Cord Blood Cholesterol, Triglyceride, and Lipoprotein Pattern from Two Districts in Norway

Lipid levels of cord blood from two districts in Norway were studied. Although the mean levels of cholesterol and triglycerides in the two populations were similar, high cord blood lipid levels were more frequently found in a population in Finnmark in northern Norway than in Bergen in western Norway. In Bergen the 95-percentile value for both cholesterol and triglycerides was 90 mg/100 ml. In Finnmark the corresponding values were 100 and 115 mg/100 ml. The lipid levels in cord blood from children of Norwegian, Finnish, and Lappish origin were nearly identical. The frequency of lipoprotein subfractions as distinct bands between beta and pre-beta fractions in polyacrylamide gel electrophoresis was the same in the two populations. Thus no genetic difference was found in lipoprotein patterns of cord blood in the populations of western and northern Norway.