Homogeneous assay for measuring low-density lipoprotein cholesterol in serum with triblock copolymer and alpha-cyclodextrin sulfate

We have developed a fully automated method for measuring LDL-cholesterol (LDL-C) in human serum without the need for prior separation, using a nonionic surfactant, polyoxyethylene-polyoxypropylene block copolyether (POE-POP), and a sodium salt of sulfated cyclic maltohexaose, alpha-cyclodextrin sulfate. Of the surfactants tested, POE-POP with a higher molecular mass of the POP block and a greater hydrophobicity reduced the reactivity of cholesterol in lipoprotein fractions; the reactivity in descending order was LDL > VLDL > chylomicron approximately HDL. Gel filtration chromatographic studies revealed that POE-POP removed lipids selectively from the LDL fraction and allowed them to participate in the cholesterol esterase-cholesterol oxidase coupling reaction system. By contrast, alpha-cyclodextrin sulfate reduced the reactivity of cholesterol, especially in chylomicrons and VLDL. A combination of POE-POP with alpha-cyclodextrin sulfate provided the required selectivity for the determination of LDL-C in serum in the presence of magnesium ions and a small amount of dextran sulfate without precipitating lipoprotein aggregates. There was a good correlation between the results of LDL-C assayed by the proposed method and the beta-quantification reference method involving 161 sera with triglyceride concentrations ranging from 0.3 to 22.6 mmol/L.     

Total cholesterol and high-density lipoprotein cholesterol in patients with non-insulin-dependent diabetes mellitus

Non-insulin-dependent diabetics often have quantitative changes in plasma lipid profiles characterised by higher triglycerides and lower HDL-cholesterol than the average population. This paper summarises the cross-sectional data (reported by the general practitioners participating in Medicos-Sentinela) concerning total and HDL-cholesterol in a cohort of non-insulin-dependent diabetics treated at primary care settings in Portugal. Total cholesterol and High Density Lipoprotein (HDL) associated cholesterol were significantly higher in women. Total cholesterol increased significantly with age (in women), regular alcohol intake, body mass index, systolic blood pressure and diastolic blood pressure (in males). HDL-cholesterol showed significant increase with age (both sexes and males only), gender, and alcohol intake in males. The increase in total cholesterol found in patients with regular alcohol intake is an infrequently reported finding.     

Comparison of 2 homogeneous high-density lipoprotein cholesterol assays

BACKGROUND: High-density lipoprotein cholesterol (HDL-C) is an independent inverse risk factor for coronary artery disease. Current methodologies for measurement of HDL-C in most clinical laboratories involve chemical precipitation-based methods. However, these methods are time-consuming, affected by high triglycerides, are not suitable for complete automation, and require a large sample size. New direct homogeneous methods are now available that do not have these constraints. DESIGN: We evaluated the performance of 2 direct homogeneous methods, Liquid N-geneous HDL-C assay (LN-HDL) and Boehringer Mannheim HDL Cholesterol assay (BM-HDL), and compared these methods against a modified Centers for Disease Control and Prevention reference method (MR-HDL) in 126 patients with normotriglyceridemia (triglycerides < 4.5 mmol/L, range 0.6-4.3 mmol/ L) and 50 patients with hypertriglyceridemia (triglycerides > or =4.5 mmol/L, range 4.5-18.8 mmol/L). RESULTS: Excellent precision profiles were exhibited by both homogeneous methods. Both LN-HDL and BM-HDL correlated well with MR-HDL in normotriglyceridemia (r = 0.98, slope = 0.93 and r = 0.97, slope = 1.0, respectively). However, compared with the modified reference method, the LN-HDL correlated better than the BM-HDL in hypertriglyceridemic samples (r = 0.97, slope = 1.0 and r = 0.91, slope = 0.9, respectively). The 1998 National Cholesterol Education Program guidelines for accuracy (bias < +/-5%) were met by LN-HDL in both normotriglyceridemic and hypertriglyceridemic samples (bias = 1.3% and 3.3%, respectively); however, BM-HDL failed to meet the National Cholesterol Education Program accuracy criteria in both triglyceride subgroups (bias = 8.2% and 11.3%, respectively). In addition, the total error for LN-HDL in both normotriglyceridemia (6.6%) and hypertriglyceridemia (8.6%) was well within the National Cholesterol Education Program guidelines for total error (< or =13%); BM-HDL exhibited a higher total error than LN-HDL in normotriglyceridemia (11.9%) and failed to meet the National Cholesterol Education Program guidelines in hypertriglyceridemia (15.0%). CONCLUSION: Although both homogeneous methods are precise, the LN-HDL assay is superior in accuracy to the BM-HDL assay when compared with the modified reference method.     

Streptozotocin-induced diabetic cynomolgus monkey is a model of hypertriglyceridemia with low high-density lipoprotein cholesterol

BACKGROUND: Cardiac allograft rejection is accompanied by cellular infiltration and tissue edema resulting in myocardial relaxation abnormalities. Doppler tissue imaging is capable of measuring myocardial relaxation velocities and is useful in the detection of heart rejection. However, the influence of ventricular loading conditions on myocardial relaxation velocities has not been studied. This study is performed to determine whether myocardial relaxation velocities are affected by left ventricular loading conditions. METHODS: Twenty heart transplant recipients without evidence of rejection by endomyocardial biopsy underwent preload and afterload reduction with nitroglycerin. The pulmonary wedge pressure was reduced from 18.2+/-0.9 to 12.0+/-0.9 mm Hg 9 (p=0.001) and the mean blood pressure from 130.0+/-5.6 to 116.1+/-7.0 mm Hg (p=0.001). Pulsed-wave Doppler tissue imaging was performed before and after administration of nitroglycerin, and the peak myocardial relaxation velocities of the inferior wall were measured. RESULTS: Myocardial relaxation velocities did not change with the administration of nitroglycerin; 0.188+/-0.009 to 0.178+/- 0.006 m/sec (p=0.4) in spite of a significant reduction in pulmonary capillary wedge pressure. Furthermore, there was no correlation between pulmonary capillary wedge pressure, mean arterial pressure, wall stress, and myocardial relaxation velocities. CONCLUSIONS: Loading conditions on the left ventricle have no influence on myocardial relaxation velocities. Therefore in heart transplant recipients changes in myocardial relaxation velocities by Doppler tissue imaging may be useful in the diagnosis of rejection, in spite of diverse loading conditions.     

Defining specific goals of therapy in treating dyslipidemia in the patient with low high-density lipoprotein cholesterol

Because patients with low high-density lipoprotein (HDL) cholesterol (HDL-C) are at high risk for clinical coronary artery disease (CAD) events, these patients require aggressive treatment with lifestyle modifications-increased exercise, smoking cessation, and weight loss in overweight patients-and available pharmacological agents. Drugs that raise HDL-C include nicotinic acid, fibric acid derivatives, estrogens, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins), alpha-blockers, and alcohol. However, all agents that increase HDL-C may not have the same clinical benefit, just as, as shown in genetic studies in humans and mice, genetic causes of high HDL-C do not always protect against CAD, nor do genetic causes of low HDL-C always increase risk for CAD. Better understanding of the complexities of HDL metabolism and the mechanisms by which HDL protects against CAD is needed to enable the development of new therapeutic strategies--novel drugs or gene delivery systems--to increase HDL-C and reduce CAD events. The statins are the agents with the greatest evidence for slowing progression of CAD and reducing clinical events in patients with low HDL-C, but additional research is needed to determine the potential benefits of additional interventions that increase HDL-C, including combination therapy, which may provide greater improvements in the entire lipid profile.     

Total cholesterol and high-density lipoprotein levels as risk factors for increased intraocular pressure

PURPOSE: To determine whether high-density lipoprotein and total cholesterol levels were risk factors for increased intraocular pressure in patients with chronic open-angle glaucoma or ocular hypertension. METHODS: We measured total cholesterol, high-density lipoprotein, and total cholesterol/high-density lipoprotein ratio in 25 patients with open-angle glaucoma or ocular hypertension who had taken no glaucoma medications for four weeks. We individually matched these patients to 25 control subjects who had no history of open-angle glaucoma or ocular hypertension, on the basis of age, race, gender, and history of vascular disease or diabetes mellitus. RESULTS: We found no statistical difference in the high-density lipoprotein (P = .702) or total cholesterol (P = .177) levels or total cholesterol/high-density lipoprotein ratio between groups (P = .178, paired t test). CONCLUSION: This study indicates that increased high-density lipoprotein and total cholesterol levels are not risk factors for increased intraocular pressure.     

Major proteins of bovine seminal plasma and high-density lipoprotein induce cholesterol efflux from epididymal sperm

One of the hypotheses to explain the mechanism of capacitation involves the loss of sperm membrane cholesterol. Here, we studied whether or not the major proteins of bovine seminal plasma designated as BSP-A1, -A2, -A3, and -30-kDa (collectively called BSP proteins), which are implicated in sperm capacitation, induce cholesterol efflux. When epididymal sperm were labeled with [3H]cholesterol and incubated with bovine seminal plasma (0.05-2%) or BSP proteins (20-120 microg/ml) for 8 h, the sperm lost [3H]cholesterol (3.6-fold and 3-fold, respectively). The same results in the presence of BSP-A1/-A2 were obtained (3.5-fold) by direct determination of cholesterol on unlabeled epididymal sperm. Analysis of efflux particles by ultracentrifugation on a sucrose gradient revealed a single symmetrical peak of radioactivity at 1.14 g/ml. Immunoblotting of the fractions obtained from size-exclusion chromatography of the efflux particles showed that a portion of the BSP proteins were associated with [3H]cholesterol. Heparin (12 microg/ml) alone did not stimulate cholesterol efflux. In contrast, high-density lipoprotein (HDL, 100 microg/ml) alone stimulated cholesterol efflux up to 3.1-fold after 8 h. When labeled epididymal sperm were preincubated for 20 min with BSP-A1/-A2 (120 microg/ml), washed, and incubated with HDL (100 microg/ml) for 8 h, the total cholesterol efflux of the sperm suspension was 51.8 +/- 5.0% compared to 39.3 +/- 1.2% when HDL alone was used. These results indicate that BSP proteins and HDL play an important role in the sperm sterol efflux that occurs during capacitation. Furthermore, the heparin-induced sperm capacitation did not involve the efflux of sperm membrane cholesterol.     

Clinical characteristics and coronary risk factors of patients with low concentrations of serum low-density lipoprotein cholesterol and total cholesterol

We investigated the clinical characteristics and coronary risk factors of Chinese patients with suspected coronary artery disease (CAD) having low serum concentrations of both low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC). Of 1,450 patients with suspected CAD (age range, 30-92 years; 948 men and 502 women), 760 had established CAD. The patients were divided into three groups according to lipid profile patterns. Group 1 patients (n = 138) had low LDL-C concentrations (< 100 mg/dL) and low TC concentrations (< 160 mg/dL). They were characterized by lower triglyceride concentrations, lower frequencies of high TC/high-density lipoprotein cholesterol (HDL-C) ratios (> 5) and LDL-C/HDL-C ratios (> 5), and lower frequencies of a family history of CAD and obesity. Group 3 patients (n = 610) had LDL-C concentrations of 130 mg/dL or above and TC concentrations of 200 mg/dL or above, much higher than in group 1. The prevalence of CAD was 41.3% (57/138) in group 1. 46.7% (328/702) in group 2, and 61.5% (375/610) in group 3. Groups with higher TC and LDL-C concentrations had a higher CAD prevalence. Coronary risk factors of group 1 patients appeared to be low HDL-C concentration, high TC/HDL-C ratio, advanced age, cigarette smoking, hypertension, and diabetes mellitus. Among these risk factors, HDL-C and hypertension were independent predictors of CAD. Unlike in the other two groups, hypertension was the only independent nonlipid risk factor. We conclude that in therapy or prevention of CAD, the goals should be to reduce LDL-C concentration to below 100 mg/dL and the TC concentration to below 160 mg/dL. However, other risk factors should also be considered.     

HDPE管道施工工艺

HDPE管是以高密度聚乙烯为原料的一种新型轻质塑料管材,具有质量轻、耐高压、韧性好、寿命长、便于运输等特点.其优异的管壁结构设计,与其他结构的管材相比,成本大大降低,并且由于连接方便、可靠,在国内外得到广泛应用.     

Association of body mass index, blood pressure and serum levels of triglycerides and high-density lipoprotein cholesterol in childhood with the insulin sensitivity index in young adulthood: a 13-year follow-up

The 77 (47 females, 30 males) in-patient referrals to the Psychiatric Department of the University College Hospital, Ibadan, Nigeria, over a 1-year period, were compared with a control sample of 75 (45 females, 30 males) unreferred patients. The low referral rate of 0.8%, after excluding deliberate self-harm (relatively infrequent in Nigeria), was comparable to reports in Western literature. Treatable minor psychiatric morbidity, mainly anxiety and depressive disorders, occurred in 41.3% of the controls. Sixty-eight percent of those referred had definite mental disorders, most commonly psychoses (50.7%), especially delirium (29.9%). Infectious disorders, notably Salmonella typhi infection, were the most predominant physical etiological factors. The results are discussed and the implications highlighted.     

Interaction of apolipoprotein AII with the putative high-density lipoprotein receptor

There is strong evidence to indicate that binding of HDL by cells is due to recognition of apoproteins residing on the surface of the lipoprotein by the putative HDL receptor(s). Although both of the major HDL apoproteins, AI and AII, are recognized by the putative receptor, the nature of the binding interaction and the domains of the apoproteins involved are largely unknown. Previous data from this laboratory led to the proposal of a model to explain how HDL particles containing AII interacted with the HDL receptor in a different manner as compared to HDL particles which contain apoAI but not apoAII [Vadiveloo, P. K., & Fidge, N. H. (1992) Biochem. J. 284, 145-151]. The model predicted that each chain of the apoAII homodimer contained a binding domain capable of interacting with the HDL receptor. This model was tested in the current study by preparing apoAII monomers, complexing them with phospholipid, and determining the ability of these complexes to bind to putative HDL receptors in rat liver plasma membranes (RLPM) and bovine aortic endothelial cell membranes (BAECM) by ligand blotting. The data showed that these complexes were bound by HB1 and HB2 from RLPM, and to the 110-kDa HDL binding protein from BAECM, providing critical evidence to support the model. Further investigation into the binding interaction revealed that apoAII complexed with phospholipid (apoAII-PC) bound more than delipidated apoAII, which bound more than delipidated apoAII monomers. Thus, optimum binding required the presence of lipid.(ABSTRACT TRUNCATED AT 250 WORDS)     

Niacin decreases removal of high-density lipoprotein apolipoprotein A-I but not cholesterol ester by Hep G2 cells. Implication for reverse cholesterol transport

Increasing the expression of c-FMS (colony-stimulating factor 1 receptor) by introduction of a transgene reduced the concentration of retinoic acid or 1,25-dihydroxy vitamin D3 needed to cause myeloid or monocytic cell differentiation and hypophosphorylation of the retinoblastoma tumor suppressor protein (RB) typically associated with cell cycle G0 arrest and differentiation of HL-60 human myelo-monoblastic precursor cells. The data are consistent with a model in which signals originating with retinoic acid and c-FMS integrate to cause differentiation, RB hypophosphorylation, and G0 arrest. Furthermore, these two signals can compensate for each other. Three HL-60 sublines described previously (A. Yen et al., Exp. Cell Res., 229: 111-125, 1996) expressing low (wild-type HL-60), intermediate, and high cell surface c-FMS were treated with various concentrations of retinoic acid. The lowest concentration tested, 10(-8) M, induced significant differentiation of only the high c-FMS-expressing cells, with no accompanying hypophosphorylated RB or G0 arrest. The low and intermediate c-FMS expressing cells showed no induced differentiation, hypophosphorylation of RB, or G0 arrest. A 10-fold higher retinoic acid concentration, 10(-1) M, induced significant differentiation of both intermediate and high c-FMS-expressing cells. It induced RB hypophosphorylation only in high c-FMS-expressing cells but with no accompanying G0 arrest in any of the cells. The highest retinoic acid concentration, 10(-6) M, elicited differentiation, hypophosphorylation of RB, and G0 arrest in low, intermediate, and high c-FMS-expressing cells. As the concentration of retinoic acid increased, cell differentiation, hypophosphorylation of RB, and G0 arrest were progressively elicited within this ensemble of cells with different c-FMS expression levels. Thus, for example, at the lowest concentration of retinoic acid, expression of high enough c-FMS still allowed differentiation. At higher concentrations, progressively less c-FMS was needed for differentiation. The apparent threshold for the sum of the retinoic acid plus c-FMS originated signals to elicit differentiation, hypophosphorylation of RB, and G0 arrest increased, in that order. Thus retinoic acid-induced cell differentiation, RB hypophosphorylation, and G0 arrest have different signal threshold requirements. 1,25-Dihydroxy vitamin D3, also a ligand for a member of the steroid thyroid hormone receptor superfamily, caused monocytic differentiation with a similar c-FMS dependency, indicating that these effects characterize both myeloid and monocytic differentiation.     

Low-density lipoprotein size, high-density lipoprotein concentration, and endothelial dysfunction in non-insulin-dependent diabetes

We examined endothelial function (nitric-oxide mediated) in 29 men with diet-treated non-insulin-dependent (Type 2) diabetes mellitus (NIDDM) and 18 male age-matched controls. Forearm blood flow was measured by venous occlusive plethysmography during intra-arterial administration of acetylcholine (ACh, 7.5 and 15 microg min(-1)) and sodium nitroprusside (SNP, 3 and 10 microg min(-1)). LDL particle size was estimated by non-denaturing gel electrophoresis. Serum lipids, blood pressure, and glycated haemoglobin were also measured. LDL particle size was smaller (p = 0.048) in the diabetic patients than controls. In the diabetic patients, LDL particle size was a significant positive predictor (p = 0.01) of the area under the dose-response curve for ACh, after adjusting for age, HbA1c, systolic BP, and cholesterol (R2 0.20). In stepwise regression including serum lipid and lipoprotein concentrations and LDL particle size, decreased HDL cholesterol was the best predictor of an impaired vasodilatory response to ACh. Vasodilatory responses to sodium nitroprusside were not significantly correlated with LDL particle size or serum lipid and lipoprotein concentrations. We conclude that in men with NIDDM, small, dense LDL particle size is associated with abnormal endogenous release of nitric oxide. The contribution of small, dense LDL particles to the development of endothelial dysfunction and early diabetic vasculopathy may not, however, be as great as decreased HDL cholesterol.     

The use of high-density polyethylene implants in facial deformities

OBJECTIVE: To determine the usefulness of porous high-density polyethylene implants (Medpor) in a variety of facial skeletal deformities and subcutaneous defects, excluding those associated with acute maxillofacial trauma. DESIGN: Case series. SETTING: Academic tertiary care referral center in Baltimore, Md. PATIENTS: Thirty-four patients (age range, 20-74 years) with facial deformities requiring skeletal defect reconstruction or augmentation (38 cases), treated between January 1, 1992, and January 1, 1997. Follow-up ranged from 6 months to 40 months. MAIN OUTCOME MEASURES: Age, type and origin of the deformity treated, type of treatment, and complications. RESULTS: Types of deformities and defects treated include 7 patients with orbital defects (secondary traumatic or oncologic deformities), 8 with temporal fossa defects, 8 with frontocranial defects, 4 with maxillary or malar defects, 7 with calvarial bone graft donor site defects, 2 with microtia, and 2 with chin deficiency. Forty implants were placed. Complications included implant exposure in 4 patients and inappropriate augmentation in 1 patient (chin implantation). CONCLUSIONS: High-density polyethylene implants offer an excellent alternative to autogenous and other alloplastic materials in reconstruction of many facial defects and deformities. Advantages include its versatility and relatively ideal pore size that allows for excellent soft tissue ingrowth and coverage. Disadvantages include its rigid nature and difficulty in contouring to the surface of complex skeletal structures.