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Biomedical subjects

R Poledne

Publications and source records attributed to R Poledne.

At least 19 recordsLinked to original sources
PubMed2006

Gaining insight from flexible models--assessment of the secondary prevention trial of CHD in the Czech male population with MI history.

OBJECTIVES: We present results from a secondary prevention trial of coronary heart disease (CHD) in the Czech male population from northern Bohemia with the history of myocardial infarction (MI) and high prevalence of metabolic syndrome. We compare several approaches to analyzing survival data from our study in terms of respective model assumptions. METHODS: While both the Cox and Weibull survival regression models assume proportionality of the hazard functions over time, in many instances this assumption appears incompatible with the data at hand. Gray's implementation of flexible models using penalized splines allows for a more realistic assessment of the covariate effects which may vary over time. RESULTS: Gray's model results revealed a steady decline in the age-adjusted intervention effect over time, which remained significant until about 2.7 years of follow-up. This was in contrast with the results obtained from the Cox and Weibull models which suggested an overall risk reduction due to intervention during the total follow-up of 6.7 years. Survival estimates based on the Cox and Gray models are shown for the two treatment groups and selected sample quantiles of the age distribution for illustration. CONCLUSIONS: Gray's time-varying coefficients model facilitated a more realistic assessment of the intervention effect. Using suitable historical controls with MI history the effect of intervention was found to gradully diminish over time.

Adult↗
PubMed2006

The effect of fluvastatin on cICAM-1 as a biomarker of endothelial dysfunction in patients with dyslipidemia.

AIM: Upregulation of intercellular adhesion molecule-1 (ICAM-1) expression has been suggested to play an important role in the pathogenesis of atherosclerosis. Lipid-lowering therapy with 3-hydroxy-methylglutaryl-coenzyme A reductase inhibitors reduces the incidence of atherosclerosis-related cardiovascular events. The aim of this study was to establish the effect of a 3-month treatment of fluvastatin on circulating (c)ICAM-1 and standard lipid parameters. METHODS: A total of 14 patients (6 men and 8 women), 59.7+/-11 years old, with mean systolic and diastolic blood pressure 135+/-16.3 and 81+/-9.3 mmHg, respectively, fasting plasma cholesterol 6.2+/-1 mmol/L and plasma triglycerides 2.6+/-1 mmol/L, took part in the study. The observed parameters were measured before and after 3 months of therapy. RESULTS: When comparing total cholesterolemia, low-density lipoprotein (LDL) cholesterol, and apolipoprotein B, there were significant decreases after a 3-month treatment. By contrast, no significant difference was observed when we compared the values of triglycerides, high-density lipoprotein (HDL) cholesterol, apolipoprotein A1 and, especially, of cICAM-1. Our results demonstrate the well-known capacity of fluvastatin to lower LDL- and total cholesterol; however, it failed to reduce cICAM after a 3-month treatment. CONCLUSIONS: It can be concluded that a 3-month therapy with fluvastatin does not decrease cICAM-1 levels, despite normalization of cholesterol levels. The implication is that cholesterol may not induce endothelial activation by the initial upregulation of this adhesive molecule.

Biomarkers↗
PubMed2005

Apolipoprotein AV variants do not affect C-reactive protein levels in Caucasian males.

The important role of APOAV gene variants in determination of plasma triglyceride levels has been shown in many population studies. Recently, an influence of APOAV T-1131>C polymorphism on C-reactive protein (CRP) in young Korean males has been reported. We have therefore analyzed a putative association between T-1131>C, Ser19>Trp and Val153>Met APOAV variants (PCR and restriction analysis) and CRP concentrations in 1119 Caucasian males, aged between 28 and 67 years (49.2+/-10.8 years). The frequency of C allele carriers was lower in Caucasians than in Koreans (15.5% vs. 46.2%). CRP levels did not differ between T/T homozygotes (n=946, 1.61+/-2.05 mg/l) and carriers of the C allele (n=173, 1.67+/-1.95 mg/l). Thus, in contrast to Korean males, T-1131>C APOAV variant has no effect on plasma concentrations of CRP in a large group of Caucasian males. Other APOAV variants (Ser19>Trp and Val153>Met) did not also influence plasma concentrations of CRP. APOAV variants are unlikely to be an important genetic determinant of plasma CRP concentrations in Caucasian males.

Adult↗
PubMed2004

No relation between angiotensin-converting enzyme gene polymorphism and smoking dependence.

BACKGROUND: Smoking as a major risk factor for development of cancer and cardiovascular disease is thought to be partially genetically determined. The aim of this study was to investigate whether there is an association between insertion/deletion (I/D) polymorphism in angiotensin-converting enzyme (ACE) and smoking status and the number of cigarettes smoked per week. METHODS: Using polymerase chain reaction, I/D polymorphism was evaluated in the ACE gene in 1204 male and 1375 female representative Caucasians. Information about smoking status and number of cigarettes smoked per week was collected via a questionnaire. RESULTS: Frequencies of the alleles and genotypes of ACE I/D polymorphism did not differ between smokers, past smokers and individuals who had never smoked. No association was found between ACE I/D polymorphism and the number of cigarettes smoked per week, either in males or in females. CONCLUSION: I/D polymorphism in the ACE gene does not play any role in genetic determination of predisposition to smoking.

Adult↗
PubMed2004

The influence of APOAV polymorphisms (T-1131>C and S19>W) on plasma triglyceride levels and risk of myocardial infarction.

The importance of an APOAV gene for plasma triglyceride level determination has been shown on transgenic and knockout mice. We examined whether APOAV variants are associated with plasma triglyceride levels and risk of myocardial infarction (MI). We have evaluated the influence of APOAV polymorphisms (T-1131>C and S19>W) on plasma triglycerides in 1191 males and 1368 females representatively selected from the Czech population. Triglycerides have been analysed in 1997 and 2001. Subsequently, we have analysed the genotype frequencies of the APOAV polymorphism in 435 patients with MI. T-1131>C variation in the APOAV gene affects the plasma triglyceride showing a higher level in C-1131 carriers than in T/T-1131 homozygotes. This association has been observed both in males and females (p < 0.001). Similarly, plasma triglycerides were also significantly influenced by the S19>W APOAV genotypes. In both males and females, the W19 carriers have triglycerides significantly (p < 0.001) higher compared to the S19 homozygotes. In a group of MI patients, the frequency of the rare homozygotes for at least one APOAV polymorphism (C/C-1131 and/or W/W19) was significantly higher than that in the population sample (7.4 vs 2.0%, p < 0.00001). We conclude that variations in the APOAV gene not only play a role in genetic determination of triglyceride levels but also could influence risk of MI.

Adult↗
PubMed2004

Hyperglycemia downregulates total lipoprotein lipase activity in humans.

To address the question whether an increase in insulinemia and/or glycemia affects the total activity of lipoprotein lipase (LPL) in circulation, the enzyme activity was measured after periods of hyperinsulinemia (HI), hyperglycemia (HG), and combined hyperinsulinemia and hyperglycemia (HIHG) induced by euglycemic hyperglycemic clamp, hyperglycemic clamp with the infusion of somatostatin to inhibit endogenous insulin secretion, and hyperglycemic clamp, respectively. The results obtained were compared to those after saline infusion (C). Twelve healthy normolipidemic and non-obese men with normal glucose tolerance were included in the study. At the end of each clamp study, LPL activity was determined first in vivo using an intravenous fat tolerance test and then in vitro in postheparin plasma. Whereas isolated HI had no effect on LPL activity in postheparin plasma, both HG and HIHG reduced LPL activity to 60 % and 56 % of that observed after saline infusion. Similarly, the k2 rate constant determined in intravenous fat tolerance test was reduced to 95 %, 84 %, and 54 % after periods of HI, HG, and HIHG, respectively. The activity of hepatic lipase, another lipase involved in lipoprotein metabolism, was not affected by hyperinsulinemia and/or hyperglycemia. In conclusion, our data suggest that hyperglycemia per se can downregulate the total LPL activity in circulation.

Adult↗
PubMed2004

New variants in the apolipoprotein AV gene in individuals with extreme triglyceride levels.

Animal studies (on transgenic and knock-out mice) and human association analysis assessed the importance of APOAV gene for plasma triglyceride determination. New APOAV missense variants (Val153 --> Met and Cys185 --> Gly) have been detected recently. We have analyzed these variants in 83 unrelated patients with extreme lipid parameters (triglycerides of 20.4+/-2.8 mmol/l and total cholesterol of 10.4+/-3.7 mmol/l) and in a control population group consisting of 2,559 unrelated Caucasians. In patients, the frequency of the Met153 carriers was slightly but not significantly higher (9.64 % vs. 6.49 %) compared to the population sample. This suggested that Val153 Met polymorphism in the APOAV gene does not represent an important risk factor for developing the extreme levels of plasma triglycerides. We did not detect carriers of the Gly185 allele among patients or 420 healthy individuals. We suppose that this variant is probably not present in Caucasian populations

Adult↗
PubMed2004

Quantification of intra-abdominal fat during controlled weight reduction: assessment using the water-suppressed breath-hold MRI technique.

A group of 14 healthy female subjects was studied using MRI during 2 months of life-style intervention. A series of 21 water-suppressed images was used to determine the intra-abdominal fat volume before and after the controlled loss of weight. The average weight decrease was 8.2 %, but the average relative loss of visceral fat was 20.3 %, whereas subcutaneous fat decreased by 13.4 %. A small but significant increase of insulin sensitivity (decrease in fasting insulin and blood glucose) was observed, but no changes in lipoprotein parameters were demonstrated. There was a significant negative correlation (r=-0.633, p=0.028) between the relative abdominal fat decrease and the initial amount of subcutaneous fat.

Abdomen↗
PubMed2004

[Antagonistic effect of the insertion/deletion (HpaI) polymorphism in the regulatory part of the gene for apolipoprotein CI in children with high and low levels of cholesterol].

BACKGROUND: High plasma lipids are one of the risk factor of atherosclerosis. Both environmental (diet, physic activity) and genetic factors have been implicated in the development of hyperlipidaemia. Apolipoprotein (apo) CI plays an important role in plasma cholesterol and triglycerides transport by VLDL particles. The aim of the study was to establish the role of the insertion/deletion polymorphism in apoCI gene in the determination of plasma lipids in children. METHODS AND RESULTS: Using PCR and restriction analysis (HpaI) we have measured I/D polymorphism in APOCI gene in two groups of children selected from opposite ends of the cholesterol distribution curve of 2000 children. Eighty-two children in high-(HCG) and eighty-six children in low-(LCG) cholesterolemic groups participated on the study. No significant difference was found in the frequencies of the APOCI genotypes or alleles between HCG vs. LCG. Association between LDL cholesterol and genotypes within the LCG was found--the D/D homozygotes have higher lipid level compared to the others (p < 0.05). In LCG opposite, but insignificant (p = 0.09) trend was observed. CONCLUSIONS: The widespread I/D polymorphism in the gene for APOCI determines the plasma lipid levels in childhood and it could become another important genetic marker that plays a role in the genetic determination of cholesterolemia.

Apolipoprotein C-I↗
PubMed2004

ATP-binding cassette (ABC) transporters in human metabolism and diseases.

The ATP-binding cassette (ABC) superfamily of active transporters involves a large number of functionally diverse transmembrane proteins. They transport a variety of substrates including amino acids, lipids, inorganic ions, peptides, saccharides, metals, drugs, and proteins. The ABC transporters not only move a variety of substrates into and out of the cell, but also are also involved in intracellular compartmental transport. Energy derived from the hydrolysis of ATP is used to transport the substrate across the membrane against a concentration gradient. The typical ABC transporter consists of two transmembrane domains and two nucleotide-binding domains. Defects in 14 of these transporters cause 13 genetic diseases (cystic fibrosis, Stargardt disease, adrenoleukodystrophy, Tangier disease, etc.). Mutations in three genes affect lipid levels expressively. Mutations in ABCA1 cause severe HDL deficiency syndromes called Tangier disease and familial high-density lipoprotein deficiency, which are characterized by a severe deficiency or absence of high-density lipoprotein in the plasma. Two other ABCG transporters, ABCG5 and ABCG8, mutations of which cause sitosterolemia, have been identified. The affected individuals absorb and retain plant sterols, as well as shellfish sterols.

ATP-Binding Cassette Transporters↗
PubMed2004

Polymorphisms in ABCG5 and ABCG8 transporters and plasma cholesterol levels.

ABCG5 and ABCG8 transporters play an important role in the absorption and excretion of sterols. Missence polymorphisms (Gln604Glu in the ABCG5 and Asp19His, Tyr54Cys, Thr400Lys, and Ala632Val in the ABCG8) in these genes have been described. In 131 males and 154 females whose dietary composition markedly changed and lipid parameters decreased over an 8-year follow-up study (total cholesterol decreased from 6.21+/-1.31 mmol/l in 1988 to 5.43+/-1.06 mmol/l in 1996), these polymorphisms were investigated using PCR. Plasma lipid levels and changes in plasma lipid levels were independent of the Gln604Glu polymorphism in ABCG5 and Asp19His and the Ala632Val polymorphisms in ABCG8. The Tyr54Cys polymorphism influenced the degree of reduction in total plasma cholesterol (delta -0.49 mmol/l in Tyr54 homozygotes vs. delta +0.12 mmol/l in Cys54 homozygotes, p<0.04) and LDL-cholesterol (delta -0.57 mmol/l in Tyr54 homozygotes vs. delta +0.04 mmol/l in Cys54 homozygotes, p<0.03) levels between 1988 and 1996 in females, but not in males. Male Thr400 homozygotes exhibited a greater decrease in total cholesterol (delta -0.90 mmol/l vs. delta -0.30 mmol/l, p<0.02) and LDL-cholesterol (delta -0.62 mmol/l vs. delta -0.19 mmol/l, p<0.04) than Lys400 carriers. No such association was observed in females. We conclude that Tyr54Cys and Thr400Lys variations in the ABCG8 gene may play a role in the genetic determination of plasma cholesterol levels and could possibly influence the gender-specific response of plasma cholesterol levels after dietary changes. These polymorphisms are of potential interest as genetic variants that may influence the lipid profile.

ATP Binding Cassette Transporter, Subfamily G, Mem↗
PubMed2004

The A-204C polymorphism in the cholesterol 7alpha-hydroxylase (CYP7A1) gene determines the cholesterolemia responsiveness to a high-fat diet.

The aim of the study was to ascertain whether the A-204C polymorphism in the cholesterol 7 -hydroxylase (CYP7A1) gene plays any role in determining LDL-cholesterol (LDL-C) concentration responsiveness to a high-fat diet. The concentrations of total cholesterol and LDL-cholesterol were measured in eleven healthy men (age: 30.9+/-3.2 years; BMI: 24.9+/-2.7 kg/m(2);;) who were homozygous for either the -204A or -204C allele, after 3 weeks on a low-fat (LF) diet and 3 weeks on a high-fat (HF) diet. During both dietary regimens, the isocaloric amount of food was provided to volunteers; LF diet contained 22 % of energy as a fat and 2.2 mg of cholesterol/kg of body weight a day, HF diet 40 % of fat and 9.7 mg of cholesterol/kg of body weight a day. In six subjects homozygous for the -204C allele, the concentrations of cholesterol and LDL-cholesterol were significantly higher on HF than on LF diet (cholesterol: 4.62 vs. 4.00 mmol/l, p<0.05; LDL-C: 2.15 vs. 1.63 mmol/l, p<0.01, respectively); no significant change was observed in five subjects homozygous for the -204A allele. There were no other differences in lipid and lipoprotein-lipid concentrations. Therefore, the polymorphism in the cholesterol 7alpha-hydroxylase promotor region seems to be involved in the determination of cholesterol and LDL-C responsiveness to a dietary fat challenge.

Adult↗
PubMed2004

Effect of diets on lipoprotein concentrations in heterozygous apolipoprotein E-deficient mice.

Loss of apolipoprotein E synthesis causes increased serum cholesterol concentrations and the sensitivity to high-fat diet in mice. We analyzed the changes in lipoprotein and hepatic structures in apolipoprotein E-deficient mice kept on control diet and cholesterol diets. Basal cholesterolemia of heterozygous (+/-) mice (2.2+/-0.28 mmol/l) was the same compared to wild-type (+/+) mice (2.3+/-0.15 mmol/l), but was lower compared to homozygous (-/-) mice (10.3+/-1.40 mmol/l). In +/- mice, cholesterolemia rose to 3.2 mmol/l on cholesterol diet and to 9 mmol/l on cholate diet, to 3 mmol/l and 3.6 mmol/l in +/+ mice, and to 23.4 mmol/l and 70.5 mmol/l in -/- mice, respectively. While the ratio of cholesterol/triglyceride concentrations in VLDL, IDL and LDL fractions was not increased in +/- mice and +/+ mice, it was increased in -/- mice on control diet. On the cholesterol diet, this ratio rose and was dramatically increased by cholate diet in all groups of mice. Even though cholate supplementation increased cholesterol concentration, it led to substantial toxic changes in hepatic morphology of all animals. In conclusion, one functional apo E allele in +/- mice is effective in keeping serum cholesterol concentrations in normal range on a control diet, but not on the cholesterol and cholate diets.

Administration, Oral↗
PubMed2004

[An ultrasensitive C-reactive protein assay--a new parameter in cardiovascular risk].

Elevated C-reactive protein concentration, measured by an ultrasensitive method (hsCRP), has been proved to be a risk factor for atherosclerosis progression and its complications (myocardial infarction and stroke) in otherwise healthy men and women. In patients with already diagnosed atherosclerotic disease elevated concentration of hsCRP predicts prognosis. There are multiple causes of elevated hsCRP concentration: metabolic changes (e.g. as a part of metabolic syndrome), genetic background and chronic infections. Proinflammatory effect of adipose tissue in obese individuals seems to play an important role, hsCRP levels correlate with markers of abdominal obesity. Elevated hsCRP concentrations can be lowered both pharmacologically and by a lifestyle change. This review covers current knowledge of pathophysiology of elevated hsCRP concentration and possible use of this method in clinical medicine.

Arteriosclerosis↗
PubMed2003

Apolipoprotein E and apolipoprotein CI polymorphisms in the Czech population: almost complete linkage disequilibrium of the less frequent alleles of both polymorphisms.

Apolipoproteins E and CI are the predominant components of triglyceride-rich lipoproteins. The genes are located in one gene cluster and both are polymorphic. Three allelic (epsilon2, epsilon3 and epsilon4) polymorphisms of the APOE gene influence plasma cholesterol levels. The distribution of these alleles differ between ethnic groups. PCR genotyping was used to determine the APOE and APOCI allele incidence in a representative group of 653 probands (302 men and 351 women) of Czech origin. The observed relative frequencies for the epsilon2, epsilon3 and epsilon4 alleles were 7.1 %, 82.0 % and 10.9 %, respectively, and are similar to other middle European populations. APO epsilon4 carriers have the highest and APO epsilon2 carriers the lowest levels of plasma total cholesterol (p<0.0001) and LDL cholesterol (p<0.0001). The frequency of the insertion (I) allele (HpaI restriction site present) of the APOCI polymorphism was 18.5 %. APOCI I/I homozygotes have the highest level of triglycerides (p<0.003). An almost complete linkage disequilibrium of the insertion allele of APOCI with the APOE alleles epsilon2 and epsilon4 has been detected and suggests that the deletion in the APOCI gene probably follows the deriving of all three APOE alleles on the APO epsilon3 allele background.

Apolipoprotein C-I↗