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Biomedical subjects

R Poledne

Publications and source records attributed to R Poledne.

At least 37 records · Page 2Linked to original sources
PubMed2003

[Lipid metabolism in atherogenesis].

Lipoprotein (LP) metabolism plays a pivotal role in atherogenesis. Breakdown of triglyceride (TG) rich lipoproteins, both of exogenous--chylomicrones and endogenous--very low density lipoproteiny (VLDL) produces remnant lipoproteins after repeated action of lipoprotein lipase (LPL). Atherogenity of remnant lipoprotein has been proved. Also atheroprotective high density lipoproteins (HDL) are produced from surface of TG rich lipoproteins during their lipolysis. Protective role of HDL particles in atherogenesis is manifested by reverse cholesterol transport from all extrahepatic cells to the liver including cells of the arterial wall. Plasma concentration of atherogenic low density lipoproteins (LPL) is regulated by the production rate of VLDL in the liver on the one hand and their utilization by selective LDL receptors (mainly in the liver) on the other hand. Number of functioning LDL receptors is regulated genetically (gene for own LDL receptor and gene for both ligands--apoprotein B and apoprotein E) and also by environmental factors. Diet low in saturated fat and cholesterol and rich in dietary fibres increases number of LDL receptors and consequently decreases LDL cholesterol concentration. Monocytes entering arterial wall when intravasal and then subendothelial concentration of LDL is increased absorb LDL and predominantly oxidized LDL by scavenger receptors. During this repeated process they are changed to macrophages, residual macrophages and foam cells. Production of foam cells represents a starting point in atherogenesis but their high presence is typical also for advanced vulnerable atherosclerotic lesions, which are prone to rupture producing clinical complication--myocardial infarction and stroke.

Animals↗
PubMed2003

[Inflammation mechanisms in the development and progress of atherosclerosis].

Recent studies have proved the importance of immune mechanisms participating in the genesis and progression of atherosclerosis. This review depicts the role of macrophages and the mode of their activation, the part of cytokines and T lymphocytes. Elevation of C-reactive protein and other acute phase reactants is a newly discovered characteristic of the atherosclerotic process, and their importance has been demonstrated in extensive epidemiological trials. It is now recognized that subclinical inflammation (as a consequence of an activation of immune system) can be caused by several factors: damage by acute inflammation, chronic infections, autoimmune damage (Hsp60). Genetic determination of the immune system reactivity has been intensively studied.

Arteriosclerosis↗
PubMed2003

[CD14 (C-159-->T) polymorphism and levels of C-reactive protein].

BACKGROUND: High plasma levels of C-reactive protein (involved in unspecific host defence) have been described as independent risk factor of atherosclerosis. The possible association has been analysed between the CD14C-159-->T polymorphism and plasma level of CRP. METHODS AND RESULTS: With the PCR and subsequent restriction analysis we have evaluated C-159-->T polymorphism in the CD14 gene of 166 representatively selected male Caucasians with known plasma level of CRP. The CRP was measured immunologically. A significantly higher (p < 0.01) frequency of the CD14-159TT homozygotes between the individuals with the plasma level of CRP > 2.19 mg/l (31.9%, 15 out of 47) has been detected when compared to the group with plasma level of CRP lower than 2.18 mg/l (11.9%, 5 out of 42). CONCLUSIONS: CD14 C-159-->T polymorphism could be the first described genetic marker associated with plasma level of C-reactive protein.

Adult↗
PubMed2003

Intrauterine undernutrition and programming as a new risk of cardiovascular disease in later life.

It is believed that atherogenesis is a multifactorial process, which could already start in utero. Development of atherosclerosis progresses over decades and leads to the cardiovascular morbidity and mortality in adulthood. At present, we have no exact explanation for all the risk factors acting in the pathogenesis of atherosclerosis. This review should provide an overview about the possible role of intrauterine undernutrition in the development of risk factors for cardiovascular disease. Intrauterine undernutrition leads to changes in fetal growth and metabolism and programs later development of some of these risk factors. A number of experimental and human studies indicates that hypertension as well as impaired cholesterol and glucose metabolism are affected by intrauterine growth. Intrauterine undernutrition plays an important role and acts synergistically with numerous genetic and environmental factors in the development of atherosclerosis. There is evidence that undernutrition of the fetus has permanent effects on the health status of human individuals.

Adult↗
PubMed2003

[Polymorphism in the regulatory part of the cholesterol 7 alpha hydroxylase gene in children with high and low levels of cholesterol].

BACKGROUND: High plasma cholesterol is one of the risk factors of atherosclerosis. Both environmental (diet, physic activity) and genetic factors have been concerned in the development of hypercholesterolemia. Cholesterol 7 alpha hydroxylase (CYP-7A1) is a key enzyme in the bile acid synthesis and it plays an important role in cholesterol catabolism. The aim of the study was to establish the role of A-204-->C polymorphism in CYP-7A1 gene in plasma lipid determination in children. METHODS AND RESULTS: Using PCR and restriction analysis (BsaI) we have measured A-204-->C polymorphism in CYP-7A1 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 in the study. No significant difference was found in the frequencies of the genotypes or alleles of the A-204-->C polymorphism in the CYP-7A1 gene between HCG and LCG. In HCG, C/C-204 homozygotes have the highest and A/A homozygotes the lowest levels of LDL-cholesterol (4.21 +/- 0.68 mmol/l vers. 3.69 +/- 0.60 mmol/l, p < 0.05). No associations between lipid parameters and genotypes within the LCG group were found. CONCLUSIONS: The A-204-->C polymorphism in the gene for CYP-7A1 is not the major determinant of plasma lipid levels in childhood. Its impact is expressed only on high cholesterol background.

Child↗
PubMed2002

Rare variant of apolipoprotein E (Arg136-->Cys) in a subject with normal lipid values.

During the screening of apolipoprotein (apo) E gene polymorphism with PCR and subsequent restriction analysis, we have identified a female carrier with a mutant allele Arg136-->Cys. This proband had normal lipid parameters and no history of coronary artery disease (CAD). We did not confirm the previously described connection between apo E Arg136-->Cys mutation and elevated lipid levels. In the case of this mutation, other factors (environmental and/or genetic) are important for the development of lipid metabolism disorders.

Aged↗
PubMed2002

The effect of an acute fat load on endothelial function after different dietary regimens in young healthy volunteers.

Attention has recently been focused on endothelial function after a single high-fat meal, i.e. on the anticipated direct atherogenic effect of triglyceride-rich lipoproteins. Our study was designed to investigate the effect of a low-fat diet given for four weeks followed by a high-fat diet for another four weeks. At the end of each dietary period, a noninvasive ultrasound investigation of endothelial function of the brachial artery was performed along with laboratory tests. Endothelial function was measured immediately before the dietary load and after three and six hours in 11 healthy volunteers. The results were expressed as percentage of the changes in artery diameter at rest and during hyperemia; the data were processed using computer technology. When compared to the low-fat regimen, the total cholesterol content rose after the high-fat diet from 4.28 mmol/l to 5.15 mmol/l (p<0.05) in the whole group of volunteers. There was no difference between both dietary regimens in baseline triglycerides. The brachial artery dilatation under basal conditions was 5.26+/-2.88 mm after the high-fat diet compared with the value of 3.13+/-3.01 mm (p<0.05) after the low-fat diet. When measured individually endothelial function in the whole group of volunteers in the course of the day, the degree of arterial dilatation after one month on low-fat diet was 3.13+/-3.0%, 3.88+/-2.5% and 5.23+/-3.3% at single measurement. When comparing arterial dilatation at two closest measurements, a non-significant trend, p>0.05 was seen in either case. The following values were obtained after one month on the high-fat diet: 5.26+/-2.9%, 4.47+/-1.7%, and 6.2+/-3.6%; again showing a non-significant trend of p>0.05. In this study, a single high-fat meal at the different dietary regimen did not significantly influence the vasoreactivity of the brachial artery in young volunteers.

Adult↗
PubMed2001

Metabolic effects of keto acid--amino acid supplementation in patients with chronic renal insufficiency receiving a low-protein diet and recombinant human erythropoietin--a randomized controlled trial.

Supplement with keto acids/amino acids (KA) and erythropoietin can independently improve the metabolic sequels of chronic renal insufficiency. Our study was designed to establish whether a supplementation with keto acids/amino acids (KA) exerts additional beneficial metabolic effects in patients with chronic renal insufficiency (CRF) treated with a low-protein diet (LPD) and recombinant human erythropoietin (EPO). In a prospective randomized controlled trial over a period of 12 months, we evaluated a total of 38 patients (20 M/18 F) aged 32-68 years with a creatinine clearance (CCr) of 20-36 ml/min. All patients were receiving EPO (40 U/kg twice a week s.c.) and a low-protein diet (0.6 g protein/kg/day and 145 kJ/kg/day). The diet of 20 patients (Group I) was supplemented with KA at a dosage of 100 mg/kg/day while 18 patients (Group II) received no supplementation. During the study period, the glomerular filtration rate slightly decreased (CCr from 28.2 +/- 3.4 to 26.4 +/- 4.1 ml/min and 29.6 +/- 4.8 to 23.4 +/- 4.4 ml/min in groups I and II, respectively and Cin); this however was more marked in Group II (Group I vs. Group II, p < 0.01). The serum levels of urea also declined (p < 0.01), more pronouncedly in Group I (p < 0.025). In Group I, there was a significant rise in the levels of leucine (p < 0.01), isoleucine (p < 0.01), valine (p < 0.02) and albumin (p < 0.01) and a decrease in protein-uria (p < 0.01). Analysis of the lipid spectrum revealed a mild yet significant decrease in total cholesterol and LDL-cholesterol (p < 0.02), more pronounced in Group I. In Group I, there was a decrease in plasma triglycerides (from 4.2 +/- 0.8 down to values a low as 2.2 +/- 0.6 mmol/L; p < 0.01) whereas HDL-cholesterol levels increased (from 0.9 +/- 0.1 to 1.2 +/- 0.1 mmol/L, p < 0.01). A further remarkable finding was a reduction in the serum concentration of free radicals (p < 0.01). We conclude that a KA supplementation in patients with CRF receiving LPD and EPO potentiates the beneficial effects on metabolism of proteins, amino acids and surprisingly, also lipids. Long-term co-administration of KA, EPO and LPD was also associated with a delay in progression of renal insufficiency and a reduction in proteinuria. Thus, concomitant administration of KA and EPO during a low-protein diet presents an effective treatment modality in the conservative management of CRF.

Adult↗
PubMed2001

[Plasma level of Lp(a) in patients with myocardial infarct is not controlled by the apolipoprotein E gene polymorphism].

BACKGROUND: We evaluated a two risk factors of atherosclerosis development, apolipoprotein E genotype and plasma level of Lp(a), and their association in Czech population. PATIENTS AND CONTROLS: Apo E and Lp(a) have been determined in the group of 109 men with premature myocardial infarction and compared with the population samples (301 men for apo E polymorphism and 112 men for Lp(a) evaluation). METHODS AND RESULTS: Apo E gene polymorphism was analysed by PCR with subsequent restriction analysis of the PCR product. Lp(a) concentration was measured enzymatically using the IMMUNO set. The frequency of alleles of apo E genotype in myocardial infarction patients did not significantly differ from that found in the control group. The distribution of the Lp(a) concentrations in MI patients was shifted to higher levels than in population sample (p < 0.0001). CONCLUSIONS: We have not found correlation between this two risk factors of myocardial infarction. High concentration of Lp(a) is on apo E polymorphism independent risk factor of development of myocardial infarction.

Adult↗
PubMed2001

[Polymorphisms in genes for cholesterol ester transfer protein, apolipoprotein C-III and lipoprotein lipase in children with high and low cholesterol levels] ].

BACKGROUND: High plasma lipids are one of the risk factor of atherosclerosis. The contribution of environmental and genetic factors to plasma lipids is roughly equal. Cholesterol ester transfer protein (CETP), lipoprotein lipase (LPL) and apolipoprotein (apo) CIII play an important role in plasma lipid metabolism. The aim of the study was to establish the role of polymorphisms in these genes in plasma lipid determination. METHODS AND RESULTS: Using PCR and restriction analysis we have measured Taq1 polymorphism in CETP, asparagine 291/serine polymorphism in LPL and C3238G polymorphism in apo CIII genes in two groups of children selected from opposite ends of the cholesterol distribution curve of 2000 children. 82 children in high- (HCG) and 86 in low- (LCG) cholesterol group participated in the study. No significant difference was found in the frequencies of the CETP and apo CIII genotypes between LCG and HCG. In the LCG, significantly more carriers (p < 0.05) of the LPL serine291 allele were found. CONCLUSIONS: Common polymorphisms in the CETP and apo CIII genes do not determine the plasma lipid levels in childhood. The carriers of the rare allele in the LPL gene could be genetically predisposed to low plasma lipid levels.

Alleles↗
PubMed2001

Genetic determination of plasma lipids and insulin in the Czech population.

OBJECTIVES: To evaluate the association between plasma lipids and insulin and variation in the genes for apolipoproteins (APO) E (CfoI), B (insertion/deletion), C1 (HpaI), and C3 (C-482T, C3238G) in a population-based Czech Slavonic study. DESIGN AND METHODS: In 131 men and 154 women, polymorphisms were investigated using PCR. In the same subjects plasma lipid levels and insulin were measured. RESULTS: In the women, carriers of the e4 allele had higher apoB (p = 0.03) and triglyceride (p = 0.03) compared to e3 homozygotes, whereas in the men, the effect of the e4 allele was seen on total cholesterol (p = 0.02), LDL cholesterol (p = 0.003) and apoB (p = 0.001). Compared with SP27 (insertion) homozygotes of the APOB polymorphism, women SP24 (deletion) homozygotes had higher levels of total (p = 0.003) and LDL cholesterol (p = 0.007) and apoB (p = 0.05). No significant effect was seen in the men. Women homozygous for the APOC3 -482T allele had higher insulin levels than -482C homozygotes (p = 0.03). Men homozygous for APOC3 -482T allele have the highest plasma triglyceride level (p = 0.02). The APOC1 polymorphism exhibited no significant effect on any of the parameters studied. CONCLUSIONS: In this sample, variation at the APOE, APOB and APOC3 genes play a role in determining plasma levels of insulin and lipids, and emphasize the importance of gender-associated effects in the genetic determinations.

Adult↗
PubMed2001

A possible role of apolipoprotein E polymorphism in predisposition to higher education.

A potential candidate gene that could contribute to the education process is the apolipoprotein E (apo E) gene that has been shown to correlate with memory function and memory decline. We measured apo E polymorphism in groups of probands with different levels of education selected from a population sample. In the group of probands with higher education (n = 82), 24.4% had the e4 allele, compared with 7.3% who had the e2 allele. A reverse association was found in the group that left school aged 15 (n = 36) - 8.3% had the e4 allele and 13.9% had the e2 allele. Eighty-seven percent of the probands with the allele e4 reached higher education, compared to only 54.5% with the allele e2. The difference between the groups is statistically significant (p = 0.039), and this may indicate some role for the apo E polymorphism in subjects' intelligence or ability to learn.

Adult↗
PubMed2001

Association between apolipoprotein B promotor haplotypes and cholesterol status.

Association between apolipoprotein B (apo B) promoter haplotypes and cholesterol concentration was studied in two groups of children with low and high concentrations of cholesterol. Strong linkage equilibrium was demonstrated between I/D in the signal peptide of apo B and (C-516T) polymorphism in the promotor of apo B gene, and the I/I+ allele T haplotype was associated with a low cholesterol concentration.

Apolipoproteins B↗
PubMed2001

Polymorphisms in the lipoprotein lipase and hepatic lipase genes and plasma lipid values in the Czech population.

We have determined the genotypes of two common polymorphisms in the lipoprotein lipase (S447X) and hepatic lipase (-480C/T) genes in a cohort of 285 representative selected Czech probands (131 male and 154 female), examined in 1988 and reinvestigated in 1996. The genotype distributions of both polymorphisms were in Hardy-Weinberg equilibrium and did not differ between male and female subjects. The rare allele frequency of the lipoprotein lipase polymorphism did not differ significantly from the other European populations. Compared to the German populations, the frequency of the hepatic lipase -480T allele was significantly higher in the Czech group (20% vs. 36%, p<0.0001). There were no significant associations between the lipoprotein lipase gene variants and lipid parameters measured either in 1988, or in 1996 or with changes of lipid parameters over the 8-year period. The carriers of the T-480 allele of the hepatic lipase polymorphism were found to have higher HDL cholesterol levels (p=0.02). However, this difference was confined to female subjects only. The male carriers of the -480T allele had higher concentrations of total cholesterol (p=0.03) as compared to CC-480 subjects. Both associations were observed in 1996 only. In the Slavic Czech population, a common polymorphism in the hepatic lipase gene (-480C/T), but not in the lipoprotein lipase gene (S447X), is a significant determinant of plasma HDL cholesterol in females and plasma total cholesterol in males and indicates the importance of gender-associated effects in the genetic determinations of plasma lipids.

Adult↗
PubMed2001

Hyperlipidemia and obesity after renal transplantation.

Obesity is very frequently found after renal transplantation (Tx). It may represent risk factor for development of atherosclerosis and chronic allograft nephropathy. In a prospective randomized metabolic study we monitored for a period of 12 months a total of 427 patients (pts) (M 228/F 199) aged 20-70 yrs after Tx. All patients were treated with cyclosporin A and prednisone at standard doses. We compared the findings of 118 pts with a body mass index (BMI) > or = 30 (kg/m2, Group I) with data obtained from 309 pts with BMI < 30 (Group II) one year after Tx. The mean values of the analysed parameters were as follows (Gr I vs Gr II): total cholesterol (TC): 7.2 +/- 2.4 vs 6.1 +/- 2.0, triglycerides (TG) 3.8 +/- 1.6 vs 2.6 +/- 0.6; LDL-cholesterol 4.1 +/- 1.2 vs 3.0 +/- 0.7; fasting glycemia 8.0 +/- 3.2 vs 5.2 +/- 2.0 (all mmol/L, all p < 0.01); HDL-cholesterol/TG 0.28 +/- 0.07 vs 0.38 + 0.06, p < 0.025). The mean values of corrected Ccr, cyclosporine level, Lp(a) and proteinuria did not differ significantly. There were also no statistical differences in apo E isoforms. In conclusion, our data suggest hyperlipidemia-associated obesity should be treated effectively as a high-risk factor after Tx.

Adult↗