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Biomedical subjects

V Soska

Publications and source records attributed to V Soska.

At least 19 recordsLinked to original sources

[Nuclear receptors PPARalpha].

Mechanism of the fibrates action is mediated by nuclear PPARalpha receptors (Peroxisome Proliferator-Activated Receptor). These receptors regulate a number of genes that are involved both in lipids and lipoproteins metabolism and other mediators (e.g. inflammatory mediatores). Due to PPARalpha activation by fibrates, triglycerides and small dense LDL concentration is decreased, HDL cholesterol is increased and both inflammation and prothrombotic status are reduced. These effects are very important in patients with metabolic syndrom.

Clofibric Acid↗

[The influence of long-term growth hormone replacement therapy on body composition, bone tissue and some metabolic parameters in adults with growth hormone deficiency].

A syndrome of growth hormone deficiency in adults (GHDA) is a syndrome characterised by metabolic deviations, body composition abnormalities, fatigue, decreased quality of life and some cardiovascular changes. The aim of the study was to assess the influence of the growth hormone (GH) replacement therapy on body composition, bone changes, serum lipids levels and some parameters of sugar metabolism in the course of 7-year monitoring. We followed 34 individuals of mean age of 41.73 +/- 2.49 years (mean +/- SE). Severe deficiency of GH was demonstrated by performing stimulation insulin tolerance test. Duration of treatment was 4.13 +/- 0.36 years (mean +/- SE). Patients were examined before the initiation of replacement therapy, after 6 months and further in yearly visits. To determine a statistical level of significance in individual parameters we compared initial baseline status (before drug administration) with the status in individual time intervals. The body composition was examined by anthropometric methods, bioelectric impedance and by densitometry, bone changes were examined by means of DEXA. There were no statistically significant changes of weight, but the waist circumference significantly decreased (p < 0.05), as well as the sum of skinfold thickness (p < 0.05) within the whole treatment period. The percentage of body fat mass measured by the BIA method was significantly changed after the period of 3 years (p < 0.05). Upon the densitometrical measurement of the body composition a significant decrease in kilograms of body fat mass (FM) occurred in the first year of the treatment (p < 0.05) and an increase in lean body mass (LBM) in kilograms during our complete monitoring (p < 0.05). A statistically significant increase in bone density was found in the whole-body BMD and BMC after the first year of the treatment. In the examination of peripheral bone changes a statistically significant increase in BMD occurred (expressed as a Z score) in the area of proximal femur after the first year and collum femoris after three years (p < 0.05), there was a significant increase in BMD of the lumbar spine already after one year of the treatment (p < 0.05) and changes were significant also in further four years. There were found no statistically significant changes related to the sugar metabolism. In the field of lipid metabolism a decrease of total and LDL cholesterol occurred already after a half of the year of the treatment (p < 0.05), changes were significant also in further four years. HDL cholesterol levels have had a progressive tendency, but they were not statistically significant. Positive changes of body composition, an increase in bone density and a decrease of total and LDL cholesterol were demonstrated in the course of the growth hormone replacement therapy.

Adult↗

[Dyslipidemia at the turn of the century: optimism or scepticism?].

Treatment of dyslipidaemia is one of the most important factors that decreases cardiovascular mortality and morbidity. Although we know lipid levels goals, we are not very successful in achiving them. The number of hypolipidemic substances is increasing and we have got guidelines for treatment dyslipidaemic patients. It is very important to implement this guidelines in the clinical practice. Another problem is rather poor patients's compliance both for dyslipidaemia treatment and for lifestyle changes. Pharmacologic treatment of dyslipidaemia may be limited due to its high expense. Pharmacologic treatment thus should be target to the high risk population: patients with coronary heart disease, patients with diabetes mellitus and with familial hypercholesterolaemia. In primary prevention only persons with high risk of cardiovascular event should be treated with hypolipidemic drugs.

Humans↗

[Dyslipidemia and the metabolic syndrome].

Dyslipoproteinemia is the common part of metabolic syndrome, it appears probably due tu high level of free fatty acids. The typical lipid disorders are: high trigylcerides concentration, low HDL-cholesterol level, elevation of small dense LDLs particles and elevation of apolipoprotein B100 and non-HDL cholesterol. LDL-cholesterol concentration is usually normal. This type of dyslipoproteinemia is very aterogenic. Weight reduction, diet and regular physical activity is the most effective way how to treat this type of dyslipoproteinemia. When non-pharmacologic treatment is not successful, treatment with hypolipidemic drugs is necessary to prevent atherosclerotic complications. Fibrates are recommended in typical dyslipidemia to lower high triglycerides level and to elevated low HDL-cholesterol concentration. But when high LDL-cholesterol is present, statins are needed. In some patients with combined hyperlipidemia treating with fibrate and statin together is needed to reach target lipid levels.

Humans↗

Influence of polysulfone and hemophan hemodialysis membranes on phagocytes.

The aim of the study was to compare the effect of hemophane and polysulfone membranes on the phagocyte-derived production of reactive oxygen species (ROS) as well as on neutrophil CD11b and CD62L expression in patients undergoing regular hemodialysis. The effects of hemodialysis membranes were also studied in in vitro conditions after coincubating them with differentiated HL-60 cells. ROS production was measured using chemiluminometric and flow cytometric methods. Expression of CD11b, CD62L and mitochondrial membrane potential were detected by monoclonal antibodies and by the JC-1 fluorescent probe, respectively. Depressed ROS production was observed in patients already before dialysis. Further decrease in ROS production and an increase in CD11b expression were observed especially in patients after hemophan hemodialysis. Decreased ROS production and increased CD11b expression were observed also after incubation of HL-60 cells with hemophan membranes. Mitochondrial membrane potential dropped only after incubating cells with hemophan membranes proving its more serious adverse effects in comparison with the polysulfone membrane. In conclusion, deleterious effects of hemodialysis on the metabolic activity of phagocytes were proved. Combining chemiluminescent and flow cytometric methods for the detection of ROS production and determining mitochondrial membrane potential can be useful tools for the analysis of material biocompatibility.

Aged↗

[Simvor in the treatment of hyperlipoproteinaemia].

BACKGROUND: Treatment of hyperlipoproteinaemias (HLP) is a basic step in prevention and treatment of atherosclerosis and its complications. Simvastatin is among hypolipidaemic agents a preparation for which at present there is most evidence from intervention trials. On the Czech market are at present in addition to the original one also some other preparations of simvastatin. In the submitted paper the authors present results achieved with the preparation Simvor (Rambaxy, distribution in CR Interchemia), tablets containing 20 mg simvastatin. CHARACTERISTIC OF GROUP AND METHODS: In 15 departments in the CR a total of 185 patients with HLP were examined, 98 men and 87 women, mean age 55.8 years. The patients were treated after a minimal 4-week period of non-pharmacological treatment with simvastatin 20 mg for a period of 6 weeks. The patients were subjected at the onset and end of treatment to a complete medical examination, basic parameters of lipid metabolism were assessed and a safety laboratory was involved. Facultatively in some departments additional examinations were made. RESULTS: The total cholesterol level 7.26 +/- 1.01 mmol/l declined on average by 1.64 mmol/l i.e. to 5.62 mmol/l, LDL-cholesterol declined from the original value of almost 5 mmol/l to 3.55 mmol/l. The baseline triglyceride concentration 3.07 declined by 1 mmol/l to 2.09 mmol/l, and HDL-cholesterol which was in a normal range already at the onset of treatment did not change significantly, i.e. its slight increase did not reach statistical significance. Treatment was well tolerated and in the safety laboratory no significant deviations from normal were recorded. DISCUSSION: The results achieved in our patients are as far as the investigated parameters are concerned, comparable with or even better than the results presented in the ample literature. The safety and tolerance of treatment of the investigated preparation is also very good. Unfortunately we did not have an opportunity during our short-term follow up to evaluate the influence of the investigated preparation on the incidence of cardiovascular diseases or mortality. In this respect we can only refer to positive results assembled with simvastatin in large statin intervention "megatrials". CONCLUSION: Treatment with decline of total and LDL-cholesterol and triglycerides. Treatment was well tolerated by the patients, in the safety laboratory no significant deviations were detected.

Female↗

[Screening for mutations in apolipoprotein B genes in a group of patients with hyperlipoproteinemia].

BACKGROUND: Familial defective apolipoprotein (apo) B-100 (FDB) is a common inherited metabolic disorder. Reduced binding of the apo B-100, the major protein of LDL particles, to LDL receptor results in marked hypercholesterolemia. FDB is caused particularly by an arginine to glutamine substitution at the codon for amino acid 3500 of the apo B-100. The aim of this study was to determine mutations potentially responsible for hypercholesterolemia in the apo B gene and to estimate their frequency in the group of Czech hyperlipidemic patients. METHODS AND RESULTS: The groups of 169 unrelated patients with primary isolated hypercholesterolemia (total cholesterol > or = 6.5 mmol/l, triglycerides < or = 2.3 mmol/l) and 58 unrelated patients with combined hyperlipoproteinemia (total cholesterol > or = 6.5 mmol/l, triglycerides > 2.3 mmol/l) were screened for mutations in codon 3500 region of the apolipoprotein B gene by denaturing gradient gel electrophoresis. Mutation R3500Q was detected in 20 patients with isolated hypercholesterolemia (11.8%) and in 2 patients with combined hyperlipoproteinemia (3.4%). No other mutations were found. CONCLUSION: The frequency of FDB in our group of patients with primary isolated hypercholesterolemia is high when compared with data published in other countries. We suggest that all patients with primary isolated hypercholesterolemia (total cholesterol > or = 6.5 mmol/l) in the Czech Republic should be analysed for the presence of mutation R3500Q in the apo B gene.

Adolescent↗

Comparison of the efficacy and tolerability of fluvastatin extended-release and immediate-release formulations in the treatment of primary hypercholesterolemia: a randomized trial.

BACKGROUND: A new extended-release (ER) formulation of fluvastatin 80 mg has been developed for once-daily treatment of primary hypercholesterolemia. OBJECTIVE: The purpose of this study was to compare the lipid-lowering efficacy and tolerability of fluvastatin ER (80 mg once daily) versus fluvastatin immediate-release (IR) (40 mg once or twice daily). METHODS: Following a 4-week placebo/dietary run-in period, patients with primary hypercholesterolemia type IIa or IIb (low-density lipoprotein cholesterol ILDL-C] > or = 160 mg/dL and triglycerides [TG] < or = 400 mg/dL) were randomized (2:1:1) to receive fluvastatin ER 80 mg once daily at bedtime (QPM), fluvastatin IR 40 mg QPM, or fluvastatin IR 40 mg BID for 24 weeks. Patients who had homozygous familial hypercholesterolemia; type I, III, IV, V, or secondary hyperlipoproteinemia; diabetes; or evidence of liver or renal impairment were excluded. At weeks 0, 2, 4, 8, 12, 16, 20, and 24 of the active-treatment period, levels of LDL-C, high-density lipoprotein cholesterol (HDL-C), TG, and total cholesterol (TC) were measured. RESULTS: Of the 1183 patients enrolled, 695 were randomly assigned to treatment--346 to fluvastatin ER 80 mg QPM, 174 to fluvastatin IR 40 mg QPM, and 175 to fluvastatin IR 40 mg BID. Patients were well matched between groups, with a mean age of approximately 56 years and body mass index of 27 kg/m2; 56.0% of patients (389/695) were female and 97.7% (679/695) were white. Fluvastatin ER 80 mg QPM lowered LDL-C levels significantly more than did fluvastatin IR 40 mg QPM (33.7% vs 24.4%; P < 0.001) and as effectively as fluvastatin IR 40 mg BID (33.9%). More than half of the patients administered fluvastatin ER 80 mg QPM and IR 40 mg BID achieved reductions in LDL-C levels of > or = 35%; more than half of those administered fluvastatin IR 40 mg QPM experienced reductions in LDL-C levels of > or = 25%. The mean reductions in LDL:HDL ratio, TC, and apolipoprotein B levels in the fluvastatin ER 80 mg QPM group were significantly greater than the reductions in the IR 40 mg QPM group (P < 0.001). In patients with mixed dyslipidemia, fluvastatin ER 80 mg reduced triglycerides by 21.8% (median 28%) and increased HDL-C by 14.5%. Fluvastatin ER 80 mg QPM was well tolerated, with incidences of clinically notable elevations in alanine aminotransferase, aspartate aminotransferase, and creatine kinase levels and musculoskeletal adverse events comparable to those in the IR 40 mg QPM group. CONCLUSION: The ER 80-mg formulation of fluvastatin is effective and well tolerated as a once-daily starting and maintenance treatment for primary hypercholesterolemia.

Adult↗

[The program for detection and treatment of patients with familial hypercholesterolemia (MedPed FH) in the Czech Republic].

The authors present an international MedPed project (Make early diagnoses to prevent early deaths in medical pedigrees) the task of which is to increase the number of patients with familial lipid disorders identified and adequately treated all over the world. This will lead to significant decrease of premature deaths from coronary artery disease. Primary effort has been focused on familial hypercholesterolemia. The realization of MedPed program in Czech Republic is described.

Adult↗

[Familial hypercholesterolemia: do we know how to diagnose it correctly?].

Familial hypercholesterolaemia is a serious inborn disease of lipoprotein metabolism with a high risk of early cardiovascular complications. The cause of the disease is a congenital defect of LDL receptors. In adults with familial hypercholesterolaemia practically always pharmacotherapy with hypolipaemic agents is indicated. The prerequisite for starting lifelong medication in primary prevention of ischaemic heart disease is a correct diagnosis of this disease. The latter involves in addition to clinical and genealogical examinations, above all correct interpretation of blood lipids in relation to age and the relationship of probands in the affected family. At present the diagnostic process is improved greatly by DNA analysis. The author mentions also exact clinical and laboratory criteria for classification of patients with familial hypercholesterolaemia into groups.

Adult↗

[Triacylglycerol as a risk factor in early ischemic heart disease].

Triacyglycerol levels above 2.0 mmol/l are according to contemporary findings an independent risk factor for the development of ischaemic heart disease. The triacylglycerol concentration of plasma provides information on the amount of lipoproteins, which carry also a major amount of cholesterol and which can also accelerate the process of atherosclerosis. Hypertriglyceridaemia as an independent risk factor was confirmed in particular in large epidemiological studies--the Framingham and Münster study. An increased triacyglycerol concentration implies obviously a greater risk for women than for men. From published results of intervention studies ensues moreover that reduction of triacyglycerol levels during hypolipidaemic treatment may reduce the incidence of ischaemic heart disease, coronary attacks and lead to regression of coronary atherosclerosis. In patients with hyperlipoproteinaemia therapeutic efforts should therefore focus not only on reduction of LDL-cholesterol but also on correction of hypetriglyceridaemia.

Coronary Artery Disease↗

[Ciprofibrate in the treatment of combined hyperlipoproteinemia. Results in more than 600 patients from 23 centers in the Czech Republic].

A total of 633 patients with combined hyperlipoproteinaemia from 23 centres in the Czech Republic met the criteria for assessment of the effectiveness of 3-month administration of 100 mg ciprofibrate (Lipanor) per day. The cholesterol concentration declined from the original values of 6.94 mmol/l by 13%. The drop of triglycerides was even more significant from 3.03 mmol/l by more than 41%. The relatively low HDL cholesterol at the beginning, 1.14 mmol/l, increased by 15%, while LDL-cholesterol dropped significantly by almost 12%. The classical atherogenic index expressed by the ratio of total/HDL cholesterol declined by 25%. Treatment was very well tolerated by the patients and was associated with a minimum of undesirable side-effects. Treatment with ciprofibrate is effective and safe treatment in patients with combined hyperlipoproteinaemia.

Clofibric Acid↗

[Pathophysiologic aspects of hyperlipoproteinemias].

Elevated LDL-cholesterol levels and reduced HDL-cholesterol levels are independent risk factors for the development of ischaemic heart disease. Atherosclerosis is promoted also by some particles rich in triacylglycerols, in particular intermediate density lipoproteins (IDL), partly also very low density lipoproteins (VLDL). The risk of IHD is enhanced also by subfractions of LDLIII and protracted postprandial lipaemia, characterized by an increased concentration of remnants of chylomicrons. An independent risk factor is also an increased concentration of lipoprotein(a). When evaluating the cardiovascular risk of an actual patient it is always necessary to consider in addition to blood lipid levels also other non-lipid risk factors.

Cardiovascular Diseases↗

[Pharmacotherapy of hyperlipoproteinemia].

Hyperlipoproteinaemia is one of the main risk factors of ischaemic heart disease. The centre of gravity of its pharmacotherapy with hypolipidaemic agents is secondary prevention of ischaemic heart disease. In patients in primary prevention of ischaemic heart disease pharmacotherapy is indicated only in case of high risk, if non-pharmacological treatment does not lead to achievement of target values of blood lipids. Available hypolipidaemic drugs on our market include statins, fibrates and resins. A suitable preparation should be selected with regard to the type of hyperlipidaemia. A constant part of treatment with hypolipidaemic drugs must be also non-pharmacological treatment which in the majority should precede pharmacotherapy.

Coronary Disease↗

[Effect of long-term hypolipidemia therapy on diastolic filling of the left ventricle].

In 18 patients with hypercholesterolaemia (total cholesterol > or = 6.7 mmol/l or LDL > or = 4.0 mmol/l a standard and Doppler echocardiographic examination was made before and after 27 +/- 7 months hypolipidaemic treatment leading to a drop of the cholesterol levels of at least > or = 1 mmol/l. Except for hypercholesterolaemia these patients did not suffer from any diseases with an impact on cardiac activity. Doppler echocardiography was used to measure parameters of diastolic left ventricular filling at rest and during 2-4 minutes of an isometric load. Lipid lowering therapy led to a significant drop of the deceleration half-time of early diastolic filling of the left ventricle at rest (from 88 +/- 16 ms to 74 +/- 15 ms, p < 0.01) as well as during an isometric load (from 83 +/- 31 ms to 61 +/- 31 ms, p < 0.05). The authors observed an insignificant increase of the rate of early diastolic left ventricular filling at rest (from 53 +/- 10 cm/s to 60 +/- 10 cm/s, p = ns) and during an isometric load (from 52 +/- 11 cm/s to 56 +/- 18 cm/s, p = ns). Similarly there was also an insignificant increase of the ratio of the velocity of left ventricular filling in early diastole to the rate of filling during atrial contraction (from 1.02 +/- 0.27 to 1.10 +/- 0.33 at rest and from 0.91 +/- 0.25 to 0.93 +/- 0.41 during a load, both p = ns). It may be concluded that long-term hypolipidaemic treatment in patients with hypercholesterolaemia contributes to better diastolic filling of the left ventricle.

Echocardiography, Doppler↗

[Present status of fibrates in the treatment of hyperlipoproteinemias].

Fibrates are hypolipaemic agents with a broad spectrum of action and long-term safety. They reduce the cardiovascular mortality and morbidity and can induce also regression of coronary atherosclerosis. They lower the plasma concentration of total and LDL-cholesterol, triacylglycerols, and produce a rise of HDL-cholesterol. Moreover they can reduce the level of fibrinogen, lipoprotein/a/, PAI-1, uric acid and the concentration of highly atherogenic small dense LDL3. Their effect is mediated by activation of "peroxisome proliferator-activated receptors" (PPARs) in the cell nucleus. At present we find on the market second generation fibrates as well as modern micronized medicaments of the third generation. They are indicated for treatment of patients with hypertriglyceridaemia, combined hyperlipidaemia and diabetic dyslipidemia.

Bezafibrate↗