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Publications (16)4.64 Total impact

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    ABSTRACT: Life expectancy is determined by a combination of genetic predisposition (~25%) and environmental influences (~75%). Nevertheless a stronger genetic influence is anticipated in long-living individuals. Apolipoprotein E (APOE) gene belongs among the most studied candidate genes of longevity. We evaluated the relation of APOE polymorphism and fitness status in the elderly. We examined a total number of 128 subjects, over 80 years of age. Using a battery of functional tests their fitness status was assessed and the subjects were stratified into 5 functional categories according to Spirduso´s classification. Biochemistry analysis was performed by enzymatic method using automated analyzers. APOE gene polymorphism was analysed performed using PCR-RFLP. APOE4 allele carriers had significantly worse fitness status compared to non-carriers (p=0.025). Multiple logistic regression analysis showed the APOE4 carriers had higher risk (p=0.05) of functional unfitness compared to APOE2/E3 individuals. APOE gene polymorphism seems be an important genetic contributor to frailty development in the elderly. While APOE2 carriers tend to remain functionally fit till higher age, the functional status of APOE4 carriers deteriorates more rapidly.
    Neuro endocrinology letters 11/2011; 32 Suppl 2:51-4. · 0.93 Impact Factor
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    ABSTRACT: Cardiovascular diseases remain the most important cause of death worldwide. The situation in the Czech Republic is one of the best when compared to the other countries of the former socialist block; on the other hand, we significantly lack behind when the comparison is made to south and southwest European countries. The concept of risk factors (RF) and multifactorial character of atherosclerosis as the main cause of cardiovascular diseases (CVD) is fully accepted at present. Hyperlipoproteinaemia (HLP) and dyslipidemia (DLP) are a group of high incidence metabolic diseases characterised by increased levels of lipids and lipoproteins in plasma or, in case of DLP, by unsuitable, atherogenic composition of lipids and lipoproteins in plasma. HLP and DLP are among the most important RF for the development of CVD. Mainly LDL-cholesterol (LDL-C) is perceived as a very important risk factor; successful reduction of LDL-C is linked to a reduction in cardiovascular risk. Even when LDL-C is decreased and the so-called "target values" achieved, patients are still at risk ofa CV event. This remnant risk is the so called "residual risk". The most important "rival" to LDL-cholesterol among the risk factors is the metabolic syndrome, or rather the DLP associated with the metabolic syndrome, characterised from the perspective of DLP by low levels of HDL-cholesterol and increased triglycerides with concurrent occurrence of "small dense LDL". The issue of heterogeneity and atherogenicity oflipoprotein particles in general then becomes topical. Lipoprotein (a)--Lp(a) is another important lipid risk factor that is getting a significant attention.
    Vnitr̆ní lékar̆ství 06/2010; 56(6):526-31.
  • Atherosclerosis Supplements - ATHEROSCLER SUPPL. 01/2005; 6(1):169-169.
  • Atherosclerosis Supplements - ATHEROSCLER SUPPL. 01/2005; 6(1):164-164.
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    ABSTRACT: Within the grant project patients with familial hyperlipoproteinaemias have been examined. The examination was performed in the oldest lipid clinic and research laboratory in the world. The classification of lipid metabolism disorders was based upon a detailed biochemical analysis of plasma lipids including electrophoresis and assessment of apolipoprotein levels. Then optimal treatment regimen could be established. The project was aimed to evaluate the efficacy of different treatment regimens in different types of hyperlipoproteinaemias. Biochemical parameters and mainly the impact of treatment of hyperlipoproteinaemia on morphology and function of the vessel wall was monitored. The non-invasive ultrasound measurement of the intima thickness of carotid arteries was used. For more precise diagnosis of genetically determined disorders of lipid metabolism a large scale of methods of molecular biology was introduced. These methods enable confirmation of familial hypercholesterolaemia, familial defective apolipoprotein B-100 or studying polymorphism of apolipoprotein E. The effort of the authors of the project was to maximally utilise the results of basic and applied research in formulating recommendations for everyday practice of physicians.
    Casopís lékar̆ů c̆eských 01/2001; 139 Suppl 1:13-5.
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    ABSTRACT: Familial hypobetalipoproteinaemia (FHBL) is a relatively rare inborn error of metabolism which must be considered in the differential diagnosis of hypocholesterolaemia which cannot be explained by secondary causes (severe malnutrition, generalization of neoplastic disease etc.). In the submitted paper the authors present the results assembled in a family with four heterozygotes with FHBL. The proband is a 27-year-old woman (total cholesterol (TCh) 1.70, triacylglycerols (TG) 0.20, HDL-cholesterol (HDL-ch.) 1.38, LDL-cholesterol (LDL-ch.) 0.34 all in mmol/l, apolipoprotein B (apo B) 0.25, lipoprotein(a)(Lp(a) 0.09 all in g/l, isoforms of apolipoprotein E/E3 (iso apo E). Mother (age 53 years) of the proband (TCh 3.06, TG 0.37, HDL-ch. 1.99, LDL-ch. 0.90 all in mmol/l, Apo B 0.37, Lp(a) 0.14 all in g/l, iso apo E3/E3)). Two of the proband's sisters (23 and 20 years) (TCh 3.92 and 2.55 resp., TG 0.57 and 0.23 resp. HDL-ch. 1.86 and 1.63 resp., LDL-ch. 1.80 and 0.82 resp. all in mmol/l, Apo B 0.73 and 0.37 resp., Lp(a) 0.47 and 0.63 resp. all in g/l, iso apo E2/E3 and E2/E3 resp.). The diagnosis confirms the autosomal dominant transmission. During the proband's pregnancy (during the 38th week), contrary to normocholesterolaemic women the TCh did not rise (1.43 mmol/l, the TG level (0.62 mmol/l), Apo B (0.43 and Lp(a) 0.18 all in g/l rose. According to the available literature this is the first description of FHBL in our literature and a priority investigation of plasma lipid concentrations, lipoproteins and apolipoproteins in a women with a heterozygous form of FHBL during pregnancy.
    Casopís lékar̆ů c̆eských 03/1997; 136(4):115-9.
  • Atherosclerosis 01/1997; 134(1):151-152. · 3.71 Impact Factor
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    ABSTRACT: The aim of the study was to approve the hypolipidemic potency of the new drug from the group of fibrate derivates Lipanthyl 200 M(R) (micronized fenofibrate, cps a 200 mg, Laboratoires Fournier, France) in patients with familial hyperlipoproteinemias. The drug has been administered in constant dose of 200 mg daily with the evening meal for three months. Clinical examinations and monitoring of safety laboratory have been performed in addition to complete analysis of lipids, lipoproteins and apolipoproteins during the study. The group of 30 patients consisted from 14 heterozygotes of familial hypercholesterolemia and 16 patients affected by familial combined hyperlipidemia. Levels of total, HDL- and LDL-cholesterol, triglycerides, apolipoproteins A-I and B and Lp(a) have been measured and concentrations of fibrinogen in plasma as well. Concentration of total cholesterol 8.29 +/- 1.3 mmol/l on the beginning of the study decreased after one and three months of the treatment to 6.94 +/- 1.19 resp. 6.98 +/- 1.21 mmol/l, concentration of triglycerides has been reduced from 2.86 +/- 1.29 mmol/l to 1.70 +/- 0.86 and 1.74 +/- 0.99 mmol/l respectively HDL-cholesterol raised from 1.14 +/- 0.32 mmol/l to 1.27 +/- 0.36 and to 1.34 +/- 0.37 mmol/l in contrast to decrease of LDL-cholesterol 5.88 +/- 1.53 mmol/l on the beginning of the study to 4.87 +/- 1.49 and 4.79 +/- 1.60. Apo B in plasma fall after three month period of the treatment from 1.83 +/- 0.43 g/l to 1.46 +/- 0.47 g/l. On the other hand the concentration of apolipoprotein apo A-I1.20 +/- 0.35 g/l increased to 1.40 +/- 0.32 g/l. Fibrinogen in plasma was reduced from 3.63 +/- 0.69 g/l to 2.77 +/- 0.50 g/l. Also this decrease was statistically significant. Micronized fenofibrate is a potent hypolipidemic drug with only rare side effects. It is very good tolerated by the patients. Micronized fenofibrate is particularly prescribed for combined hyperlipidemia, however we can use it also in some patients with familial hypercholesterolemia. For to the treatment very resistant hyperlipoproteinemias we should consider combined drug therapy.
    Casopís lékar̆ů c̆eských 08/1996; 135(13):413-6.
  • R Ceska, J Sobra, R Procházková, M Kvasilová
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    ABSTRACT: The association between hypercholesterolemia and premature atherosclerosis is almost universally accepted. Treatment of hyperlipoproteinemias represents a reasonable approach in preventive cardiology. The aim of the study was to prove a hypolipidemic effect of simvastatin, Zocor tablets à 10 mg, produced by MSD, U:S.A. in patients with familial hypercholesterolemia. 29 familial hypercholesterolemia heterozygotes have been treated with increasing dose of simvastatin (10 and 20 mg/day with the evening meal) for three months. All patients have been on AHA step I diet. The basic parameters of lipid and lipoprotein metabolism have been measured, as well the concentrations of apolipoproteins A-I and B, and the level of lipoprotein(a). Concentration of total cholesterol decreased after treatment with 10 and 20 mg of simvastatin by 20%, resp. 26%. The hypolipidemic effect was even more pronounced in LDL-cholesterol level, which was reduced by 24% respectively 34%. On the other hand therapy with simvastatin did not influence HDL-cholesterol at all. Also triglycerides concentration did not changed very significantly after administration of simvastatin (triglycerides levels were reduced by 7% respectively by 18%). Decline of LDL-cholesterol has been accompanied by decrease of apolipoprotein B concentration by 24%, resp. 26%. The concentration of lipoprotein (a) has not been statistically significantly influenced, even its level increased slightly. The body weight of the patients did not changed during the study. Simvastatin treatment has been well tolerated by the patients. Simvastatin, Zocor, seems to be powerful hypolipidemic drug, which is to be used even in the treatment of familial hypercholesterolemia heterozygotes, who are usually very resistant to the therapy. The dose of 10 mg of simvastatin is usually sufficient to influence plasma lipids and lipoproteins. A double dose intensifies the hypolipidemic effect but this additional effect is not so expressive. Zocor is tolerated well by the patients and in safety laboratory we did not notice any important undesirable result.
    Casopís lékar̆ů c̆eských 06/1995; 134(10):310-3.
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    ABSTRACT: Simvastatin is a hypolipidaemic agent, a statin which inhibits cellular cholesterol synthesis by blocking 3HMG CoA reductase. The authors present a report on levels of plasma metabolites of vitamin D after treatment with 10 and 20 mg simvastatin daily in 13 patients, heterozygotes with hypercholesterolaemia during a five-week period. During simvastatin treatment in all patients plasma levels, of the sum of hydroxylated vitamin D metabolites and 1,25-dihydroxyvitamin D after five weeks of treatment with 10 and 20 mg hypolipidaemic drug were examined. For assessment of vitamin D metabolites radioassay was used which assesses the sum of hydroxylated vitamin D metabolites, and radioimmunoanalysis for assessing the 1,25-dihydroxyvitamin D plasma level. For statistical evaluation the non-parametric Friedman test and simultaneous testing was used. Simvastatin raises the plasma levels of the sum of hydroxylated vitamin D metabolites and 1,25-dihydroxyvitamin D in a dose-dependent ratio. The authors recommend to monitor the plasma levels of vitamin D metabolites over a longer time period.
    Casopís lékar̆ů c̆eských 01/1995; 133(23):727-9.
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    ABSTRACT: The authors investigated in 29 patients with familial hyperlipoproteinaemia the effect of fibrate treatment (Duolip forte, Merckle, and Lipanthyl, Richter) on vitamin D metabolism. In 10 patients treated for 6 months with daily oral doses of 500 mg Duolip forte they did not prove changes of plasma levels of 25-hydroxyvitamin D, however, they recorded a rise of the 1,25-dihydroxyvitamin D3 plasma level. In 19 patients who were given for 6 months 300 mg Lipanthyl per day by the oral route they proved a significant decline of the 25-hydroxyvitamin D plasma levels and a rise of 1,25-dihydroxyvitamin D3 plasma levels. The authors maintain that fibrates influence plasma concentrations of vitamin D metabolites either directly or indirectly by reducing cholesterol plasma levels.
    Casopís lékar̆ů c̆eských 11/1993; 132(20):630-2.
  • R Ceska, J Sobra, R Procházková, M Kvasilová
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    ABSTRACT: Within the framework of clinical tests of Etolip (ethophylline clofibrate cps. 125 mg, Pharmaceutical Research Institute Modra) this preparation was administered to 28 patients with different types of hyperlipoproteinaemia in a specialized clinic for disorders of the lipid metabolism. The period of administration was four weeks, the dose 2 cps. twice a day. The effect of this new hypolipidaemic drug was compared with that of Lipathyl. Treatment with Etolip did not affect significantly the cholesterol and triacylglycerol levels, and the concentrations of apolipoprotein B and LDL-cholesterol did not change significantly. All these parameters were affected favourably and significantly by Lipanthyl. Etolip treatment had the favourable effect of elevating the HDL-cholesterol and apolipoprotein A-I level. Etolip was well tolerated by patients and no undesirable side-effects developed. The effects of Etolip as a hypolipidaemic agent are relatively small and are markedly lower than the effect of other registered hypolipidaemics available in the CSSR.
    Vnitr̆ní lékar̆ství 05/1990; 36(4):363-7.
  • R Ceska, J Sobra, P Procházková, M Kvasilová
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    ABSTRACT: In a specialized clinic for hyperlipoproteinaemias 15 patients with different types of hyperlipoproteinaemias were treated with bezafibrate (Bezalip R tablets a 200 mg of Boehringer Co.) for a period of four weeks 3 X 1 tablet per day. The administration of Bezalip led to a significant drop of cholesterol (-20%), triglycerides by 40% and LDL-cholesterol (-17%), while the HDL cholesterol level did not change significantly. During treatment a drop of the apolipoprotein B level by 17% occurred, the concentration of apolipoprotein A-I increased by 12%. The drug was well tolerated by the patients, there were no undesirable effects calling for discontinuation of treatment. The results are discussed along with those of other authors who had the opportunity to administer the drug for a prolonged period. The authors mention also briefly the results obtained during treatment of patients with hyperlipoproteinaemias, using other hypolipidaemic drugs.
    Casopís lékar̆ů c̆eských 02/1990; 129(1):20-2.
  • R Ceska, J Sobra, M Kvasilová, R Procházková
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    ABSTRACT: When studying disorders fat metabolism in respect to ischemic heart disease great attention has been recently paid first of all to the protein component of lipoprotein complexes, apolipoproteins. Apolipoproteins seem to be much more sensitive indicators of coronary atherosclerosis risk than so far commonly used "lipid" ones. In the presented study we introduce our experience concerning apolipoprotein B assessment by means of rocket technique using foreign made antisera in comparison with antiserum of the Czechoslovak production made by USOL Prague. Our results are comparable with those of foreign and Czechoslovak authors who assessed apolipoprotein B by technically more demanding methods. When using antisera USOL and Behring the established values of apolipoprotein B are comparable both in patients in whom fat metabolism disorder was not proved and in patients with familial hypercholesterolaemia in whom the values of apolipoprotein B are the highest. Indications of apolipoprotein B investigation and its significance for clinical practice are discussed.
    Sbornik lekarsky 12/1989; 91(11-12):334-8.
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    ABSTRACT: The authors examined 18 heterozygotes with familial hypercholesterolaemia and assessed vitamin D metabolites, parameters of phosphocalcium homeostasis and blood lipids. They investigated the effect of the hypolipidaemic drug lovastatin (Mevacor, Merck, Sharpe Dohme, tbl. 20 mg) on the vitamin D metabolism, using increasing doses of 20 to 80 mg per day. They found normal parameters of phosphocalcium homeostasis, normal plasma concentrations of 1,25-dihydroxyvitamin D but low basal values of 25-dihydroxyvitamin D and elevated plasma levels after three months' treatment with MEVACOR. They confirmed at the same time the hypocholesterolaemic effect of the drug. The authors conclude that heterozygotes with familial hypercholesterolaemia may suffer from vitamin D deficiency and that the positive iatropathogenic effect of MEVACOR, a substance inhibiting the activity of 3 hydroxymethylglutarate coenzyme A reductase can have a supporting effect on the vitamin D homeostasis, in particular in old people with vitamin D deficiency.
    Casopís lékar̆ů c̆eských 10/1989; 128(40):1254-6.
  • R Ceska, J Sobra, R Procházková, M Kvasilová
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    ABSTRACT: 18 patients treated at a specialized consultation centre for disorders of fat metabolism were administered a new-generation hypolipidemic (preparation lovastatin-Mevacor) produced by Merck Sharp and Dohme, which inhibits intracellular synthesis of cholesterol. The study also discusses specific types of heterozygotes with familial hypercholesterolemia representing a homogeneous group of patients with maximum resistance to medication and dietary therapy. Mevacor was administered in increasing doses of 20.40 and 80 mg daily for a three-month period. During therapy cholesterol and apolipoprotein B levels significantly decreased, the former from 10.13 to 7.19 mmol/l, the latter from 1.95 to 1.49 g/l. Protective HDL cholesterol significantly increased from 1.01 to 1.23 mmol/l without the triglyceride level indicating any significant change. The course of therapy did not result in any undesirable effects necessitating drug discontinuation. During the clinical testing the patients' weight remained unchanged.
    Casopís lékar̆ů c̆eských 06/1989; 128(21):661-3.