Conformation and elasticity of a charged polymer chain bridging two nanoparticles.

A complex composed of a charged flexible polymer chain irreversibly attached with its ends to surfaces of two nanoparticles was investigated using the Metropolis Monte Carlo method on a simple cubic lattice. The simulations were performed in the presence of explicit ions. The bridging chain and the nanoparticles bearing the same and the opposite sign charges were considered. Changes in the free energy of the complex upon its stretching or compression, together with the magnitude of the elastic force, were examined. The relative roles of energetic and entropic effects in determining the properties of the complex were identified. Also, the adsorption of charged monomers on the opposite-sign charged nanoparticles and its influence on the examined quantities was studied. Moreover, a simple semi-analytical approach to the thermodynamics of the polymer bridge was derived.

High density lipoprotein deficiency with xanthomas. A defect in reverse cholesterol transport caused by a point mutation in the apolipoprotein A-I gene.

A 7-yr-old girl with high density lipoprotein (HDL) deficiency and xanthomas has been identified in a Turkish kindred with repetitive consanguinity. She has severely reduced HDL-cholesterol and no apolipoprotein (apo) A-I. ApoA-II is reduced, whereas apoA-IV and apoC-III are normal. ApoB and low density lipoprotein (LDL)-cholesterol are increased. This is reflected in hypercholesterolemia. VLDL and IDL particles are low, and serum triglycerides are normal. The genetic defect could be identified as a base insertion into the third exon of the apoA-I gene. This leads to a nonsense peptide sequence beginning at amino acid 5 of the mature plasma protein and early termination of translation. The patient is homozygous for this mutation. Pedigree analysis indicated an autosomal dominant inheritance with no evidence of another genetic defect of lipoprotein metabolism in the kindred. In HDL deficiency, HDL binding to leukocytes was increased compared to normal. In the postprandial state, binding of labeled HDL3 to leukocytes is unchanged. This is in contrast to results with postprandially isolated leukocytes from controls or Tangier patients, which have a reduced binding capacity for HDL3. These results indicate that postprandial HDL precursors may compete the binding of labeled HDL3. The metabolic consequences of HDL deficiency were analyzed. There is only a small number of HDL-like particles containing apoA-II, apoA-IV, apoE, and lecithin/cholesteryl acyl transferase. The C-apolipoproteins were normal in the proband. Due to the lack of HDL they can only associate with apoB-containing particles, where they may interfere with cellular uptake. Thus, pure apoA-I deficiency leads to a complex metabolic derangement.

Impact of obesity and nitric oxide synthase gene G894T polymorphism on essential hypertension.

Hypertension is a multifactorial disease caused by environmental, metabolic and genetic factors, but little is currently known on the complex interplay between these factors and blood pressure. The aim of the present study was to assess the potential impact of obesity, and angiotensin-converting enzyme (ACE) I/D polymorphism and endothelial nitric oxide synthase gene (NOS3) 4a/4b, G894T and -T786C variants on the essential hypertension. The study group consisted of 1,027 Caucasian adults of Polish nationality (45.5 ± 13.6 years old), of which 401 met the criteria for hypertension. Body weight, height and blood pressure were measured and data on self-reported smoking status were collected. Fasting blood glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides were determined by standard procedures. The ACE I/D polymorphism and three polymorphisms in NOS3 gene (4a/4b, G894T, -T786C) were detected by the PCR method. Multivariable logistic regression demonstrated that age above 45 years, diabetes, dyslipidemia, smoking and male sex are important risk factors for hypertension and no significant influence of variants in ACE and NOS3 genes on this risk was recognized. Obese subjects had a 3.27-times higher risk (OR = 3.27, 95% CI: 2.37 - 4.52) of hypertension than non-obese, and in obese the NOS3 894T allele was associated with 1.37 fold higher risk of hypertension (P = 0.031). The distribution of NOS3 G894T genotypes supported the co-dominant (OR = 1.35, P = 0.034, Pfit = 0.435) or recessive (OR = 2.00, P = 0.046, Pfit = 0.286), but not dominant model of inheritance (P = 0.100). The study indicates that in obese NOS3 G894T polymorphism may enhance hypertension risk. However, in the presence of such strong risk factors as age, diabetes and smoking, the impact of this genetic variant seems to be attenuated. Further studies are needed to reveal the usefulness of G894T polymorphism in hypertension risk assessment in obese.

Influence of bezafibrate and colestipol on LDL-cholesterol, LDL-apolipoprotein B and HDL-cholesterol in hyperlipoproteinaemia.

A significant increase of LDL-apolipoprotein B by 13% and LDL-cholesterol by 19% was observed in a group of 9 patients with hyperlipoproteinaemia Type III after bezafibrate treatment. Additional administration of colestipol caused a significant decrease of both LDL-apolipoprotein B by 18% and LDL-cholesterol by 25%. In 10 patients of hyperlipoproteinaemia Type IIb a significant decrease of both LDL-apolipoprotein B by 28% and LDL-apolipoprotein B by 18% was observed after bezafibrate therapy. When bezafibrate was given together with colestipol a further decrease of both LDL-cholesterol by 17% and LDL-apolipoprotein B by 16% occurred. HDL-cholesterol concentration increased significantly in both groups of hyperlipaemic patients during therapy. This may be the effect of both bezafibrate and colestipol. It is concluded that bile acid resins may effectively prevent the LDL-cholesterol concentration increase observed sometimes after clofibrate analogues.

The effect of thermally oxidized soya bean oil on metabolism of chylomicrons. Increased uptake and degradation of oxidized chylomicrons in cultured mouse macrophages.

Oral administration of thermally oxidized soya bean oil (TO) increased the level of lipid peroxides in human plasma, mainly in chylomicrons. No changes were observed after fresh oil (FO) intake. Human chylomicrons obtained after TO ingestion were rich in lipid peroxides and degraded more rapidly by cultured mouse macrophages than chylomicrons after FO. The uptake of TO chylomicrons by macrophages occurred via a saturable process and was partially inhibited by beta-very low density lipoprotein as well as by acetyl-low density lipoprotein and fucoidin. A 48-h incubation of macrophages with TO chylomicrons caused a 10-fold higher accumulation of cholesterol ester mass in the cells than the incubation with FO chylomicrons. These studies suggest that chylomicrons containing lipid peroxides may be taken up by mouse macrophages by mediation of beta-VLDL receptor as well as by acetyl-LDL receptor, and show a potential pathway by which chylomicrons obtained after ingestion of heated oil could contribute to accumulation of cholesterol esters in macrophages.

LpAI in HDL subfractions: serum levels in men and women with coronary heart disease and changes under hypolipemic therapy.

BACKGROUND: It is generally accepted that different HDL subpopulations may vary in their antiatherogenic potential, and the identification and differentiation of individual HDL subclasses may be useful in documentation and understanding of metabolic changes of different HDL particle groups. METHODS: In the present study, LpAI particles concentrations in HDL(2) and HDL(3) subfractions were determined in serum of 54 CHD patients (33 men and 21 women) and 46 control subjects (19 men and 27 women) with similar total cholesterol and HDL-cholesterol levels. RESULTS: In CHD patients, both men and women, as compared to control subjects lower levels of LpAI subpopulations were found, however, the difference was much more predominant for LpAI-HDL(2) than for LpAI-HDL(3). The effect of hypolipidemic treatment on the distribution of LpAI subpopulations between HDL subfractions was investigated in 44 hyperlipidemic patients assigned to fenofibrate therapy and 43 patients assigned to simvastatin therapy. Fenofibrate did not change LpAI level but had an effect on LpAI particle distribution among HDL(2) and HDL(3) increasing LpAI concentration in HDL(2) and slightly decreasing LpAI concentration in HDL(3). Simvastatin led to an increase in LpAI-HDL(3) and did not change significantly LpAI-HDL(2) particle concentration. CONCLUSION: Further studies are needed to evaluate the significance of different HDL subpopulations.

Lipids in serum of patients with malignant ovarian neoplasms.

OBJECTIVE: In numerous papers, different associations of serum lipids and lipoproteins with neoplastic diseases were found. The aim of our work was to find out associations between levels of 11 serum lipids, lipoproteins and ovarian cancer. METHODS: 25 healthy women and 25 patients with ovarian cancer underwent examinations. Uni- and multivariate analysis of variance and discrimination analysis were used to analyze our results. RESULTS: The analysis demonstrates that ovarian carcinoma is associated with a significant reduction of total cholesterol and its esters in serum and in high density lipoprotein fractions compared to controls. CONCLUSION: It could be shown that using multivariate analysis of variance it is possible to find the optimal set of serum lipid parameters, containing serum esterified cholesterol, serum total cholesterol and high density lipoproteins esterified cholesterol, to differentiate healthy persons from patients affected by ovarian cancer.

[The atherogenic lipid profile parameters and fibrinogen serum concentration in climacteric women under various routes of hormone replacement therapy administration]. / Ocena stezenia aterogennych czynników lipidowych i fibrynogenu w surowicy kobiet stosujacych rózne formy hormonalnej terapii zastepczej w okresie klimakterium.

OBJECTIVES: Influence of various routes of HTR on atherogenic lipid profile parameters and serum fibrinogen concentration was investigated. DESIGN: In 85 women in four groups receiving HRT transvaginally, transdermally, orally and intramuscularly, the total cholesterol, HDL-cholesterol, triglycerides, apoB, apoA, LpA and fibrinogen serum concentration was assessed before treatment and after six month. RESULTS: Most of tested parameters: total cholesterol, LpAI, apoB, LDL cholesterol, non HDL cholesterol, changed favorably (lowered concentration) in group using HRT orally and intramuscularly. CONCLUSION: Orally and intramuscularly route of administration HRT have better cardioprotective effects.

[Effect of combined treatment with lovastatin and colestipol on serum lipids and lipoproteins]. / Wplyw skojarzonego leczenia lovastatinem i kolestipolem na lipidy i lipoproteiny surowicy.

In 20 men with hypercholesterolaemia or mixed hyperlipaemia the effect was evaluated of treatment with Lovastatin and Colestipol on lipoproteins. Administration of the drugs in combination or alone decreased significantly the concentrations of total cholesterol (TC), LDL cholesterol (LDL-chol), and apolipoprotein B (apo B). The combination of Lovastatin in dose of 40 mg with Colestipol in dose of 10 g decreased more favourably the concentrations of TC (34.7%), LDL-chol (44.3%), and apo B (22.4%) than administration of each of the drugs alone in higher doses i.e. Lovastatin 80 mg (TC--26.8%, LDL-chol--31.8%, apo B--16.9%) or Colestipol 20 g (TC -20.0%, LDL-chol-26.3%, apo B-10.8%). The treatment with Lovastatin and Colestipol failed to change significantly the concentrations of triglycerides, HDL cholesterol and AI and AII apolipoproteins. The combined therapy was better tolerated than monotherapy.

[Effect of CRP preparation on serum lipids in patients with hyperlipidemia]. / Wplyw preparatu CRP na lipidy surowicy u pacjentów z hiperlipidemia.

In a group of 18 patients with essential hyperlipidaemia the influence was studied of multivitamin CRP preparation given for 12 weeks, on lipid peroxides, cholesterol and triglycerides in the serum. The level of lipid peroxides was decreased significantly. This effect was associated with the increase of the serum level of vitamin E. A decrease was also found of the levels of total cholesterol and LDL-cholesterol.

[Granulocyte adherence in advanced Hodgkin's disease and its dependence on antiproliferative drugs used]. / Adherencja granulocytów w zaawansowanych okresach choroby Hodgkina i jej zaleznosc od stosowanych leków antyproliferacyjnych.

In 36 patients with stage III and IV of Hodgkin's disease granulocyte adherence was investigated. The determinations were carried out in minicolumns filled with nylon fibres. In 13 patients the determinations were repeated 2, 4, 6, 12 and 24 hours after administration of vinblastine and cyclophosphamide. In all patients granulocyte adherence was reduced, by 54.1 +/- 3.5% on the average. The values of adherence in the control group were of the order of 83.7 +/- +/- 4.7%. Administration of antiproliferative drugs reduced further the adherence. The lowest value of it was observed 6 hours after vinblastine and cyclophosphamide administration. After that time the adherence increased gradually reaching the initial level 24 hours after administration of antiproliferative agents. These results suggest that reduced adherence of granulocytes may be an additional cause, besides abnormal immunological reactions, of the impairment of the resistance mechanisms of the organism in advanced stages of Hodgkin's disease.

[Usefulness of hydrocortisone test for assessment of bone marrow reserve in neutrophils]. / Przydatnosc testu hydrokortzonowego dla oceny wielkosci rezerwy szpikowej granulocytów obojetnochlonnych.

The activity of lysozyme and unsaturated binding capacity of vitamin B12 in the serum were determined in hydrocortisone test for calculating the reserve of granulocytes in bone marrow. A significant rise in the count of neutrophils in peripheral blood 3 hours after the beginning of the test was not associated with statistically significant changes in the determined parameters. This in an evidence that prolongation of the survival of cells in the circulation as one of the mechanisms of corticosteriod action on the granulocyte system is without any greater importance. This is connected, most probably, with short duration of the test. The rise of neutrophil count in peripheral blood after hydrocortisone administration may be regarded, therefore, as a measure of the value of one marrow reserve of these cells.

Spontaneous processes and stable structures in some three-phase cellular fluids.

Cellular fluids are systems consisting of a collection of fluid cells surrounded by thin liquid films. In this study, systems composed of two different kinds of cells (i.e., filled with fluids A and B) immersed in a third fluid phase (a liquid C) have been examined. The object of the study is a collection of polyhedra of fluid B separated by a thin film of liquid C (a host B/C network), modified by the insertion of small droplets/bubbles of fluid A. Interfacial tensions acting along the A-C and B-C interfaces are assumed to be the only driving forces determining the structure of the resulting mixed system. Different configurations of mixed A/B/C systems, formed by the insertion of A singlets or doublets into the nodes, edges, films and interior parts of cells of the B/C network have been analyzed in terms of the interfacial energy of the system. The possibility of spontaneous migration of cells A through the B/C network and the possible final cell arrangements have been examined.