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Biomedical subjects

R Ceska

Publications and source records attributed to R Ceska.

At least 19 recordsLinked to original sources

Decrease in serum dehydroepiandrosterone level after fenofibrate treatment in males with hyperlipidemia.

The influence of steroid hormones on plasma lipids and lipoproteins was confirmed by many studies. On the other hand, the effect of plasma lipids on metabolism of steroid hormones has so far not been examined. The objective of this research project was to determine (1) the levels of cortisol, testosterone, estradiol, dehydroepiandrosterone (DHEA), its sulfate (DHEAS), 7-hydroxylated DHEA, and SHBG in men suffering from mixed hyperlipidemia (HPL) (n=23, age 46.1+/-7.9 years) in comparison with healthy male volunteers (n=17, age 45.1+/-15.6 years); (2) whether therapy with fenofibrate influences the levels of the above mentioned steroids and SHBG; (3) what are the correlations between lipids and steroids in healthy males and HPL patients before and after therapy. Compared to controls, untreated patients had significantly higher estradiol and free testosterone index (IFT) levels (p<0.0003 and p<0.02, respectively) and significantly lower SHBG (p<0.02). Due to fenofibrate therapy, a significant decrease of TC, TG, and DHEA levels occurred (mean decrease: 14 %, 52 % and 21 %, respectively). Triglycerides correlated negatively with testosterone and SHBG in healthy subjects. HDL-C correlated positively and consequently, atherogenic index correlated negatively with 7-hydroxylated epimers of DHEA in treated patients. This is the first study dealing with the influence of fenofibrate administration on the steroid levels. Taking together, the most important is the finding of decrease DHEA levels after fenofibrate therapy. It could be explained, at least in part, by the effect of the fenofibrateon on the biosynthesis of DHEA and its regulation.

Adult↗

[Recommendations for the treatment of tobacco dependence].

This first Czech version of guidelines formulated by the working group of mentioned medical associations is based on current literature and international guidelines. They are aimed mainly on clinical medicine and on incorporation of this treatment into the health care system according to WHO recommendations. They should serve to the treatment of tobacco dependence at any level: during any contact with the smoking patient (short intervention), in specialised centres or for the health care providers or health system itself.

Humans↗

Matrix metalloproteinases in isolated hypercholesterolemia.

AIM: Levels of circulating matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are altered in subjects with atherosclerosis. We hypothesized that also otherwise healthy hypercholesterolemic subjects will have altered MMP/TIMP concentrations. To validate this hypothesis, we compared MMPs/TIMPs in patients with moderate isolated hypercholesterolemia before and after atorvastatin therapy and in healthy normolipidemic controls. METHODS: Twenty-seven otherwise healthy subjects with isolated hypercholesterolemia (total cholesterol 8.3+/-0.3 mmol/L) and 29 healthy normolipidemic controls were included. Patients were treated by atorvastatin for 10 weeks. We studied plasma levels of MMPs (MMP)-2, -3, and -9 and of their TIMPs (TIMP)-1 and -2. RESULTS: Patients differed from controls by significantly lower MMP-3 [11.6 (5.7-21) vs 18.4 (12-22) ng/mL, P<10-4 (median, range 25-75%)] and TIMP-2 [13.3 (8.8-30.5) vs 22.1 (10.8-39) ng/mL, P=0.02] and by higher TIMP-1 [496 (461-538) vs 483 (456-500) ng/mL, P=0.004]. Atorvastatin decreased significantly TIMP-1 [from 496 (461-538) to 476 (451-525) ng/mL]. CONCLUSIONS: Isolated hypercholesterolemia per se is associated with similar alterations of circulating MMPs and TIMPs as developed symptomatic atherosclerosis. Most consistent link to serum lipids was observed in case of TIMP-1. MMP and TIMP levels probably reflect the atherogenic process in its early stages in these subjects.

Atherosclerosis↗

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↗

[Serum lipids in drug addicts].

UNLABELLED: The background and aim is to study profile of serum lipids in drug addicts using heroin. METHODS AND RESULTS: The study involved 107 drug addicts using heroin (83 men and 24 women). Mean age was 29.3 years (variation 20-47 years). Mean time of using heroin was 6.5 years. Serum lipids (total cholesterol, HDL-cholesterol, triacylglycerol) were measured using enzyme methods. LDL-cholesterol and Body Mass Index (BMI) were calculated. All parameters were significantly decreased (mean levels of total cholesterol 4.31, triacylglycerol 1.29, HDL-cholesterol 1.08 and LDL-cholesterol 2.70 mmol/l). Levels of HDL-cholesterol under 1.0 mmol/l were found in 32%. Statistical measurments were performed by t-test and results compared with control group. CONCLUSIONS: Levels of HDL-cholesterol lower than 1.0 mmol/l (32%) are of importance and patients must be further controlled.

Adult↗

Increase of inflammatory state in overweight adults with combined hyperlipidemia.

BACKGROUND AND AIM: Elevated levels of acute phase reactants are found in patients with cardiovascular disease. It is suggested that adipose tissue is a determinant of a low level of inflammatory state in overweight persons. The aim of the study was to determine, whether combined hyperlipidemia, which is an important factor of atherosclerosis, has influence on the inflammatory response in overweight adults. METHODS AND RESULTS: Levels of soluble cell adhesion molecules sICAM-1, sE-selectin and sP-selectin, PAI-1 Ag (by Elisa test), orosomucoid (ORM) and transferrin (TRF) (by microturbidimetry) and fibrinogen (FBG) according to Clauss were examined in peripheral blood of overweight adults (n 33, body mass index 27.1 +/- 1.8 kg/m2) with combined hyperlipidemia and in equal numbers of age, sex and BMI matched non-hyperlipidemic group. Overweight adults with combined hyperlipidemia had significantly higher plasma levels of sICAM-1 (376.5 +/- 107.4 ng/mL vs 239.3 +/- 60.4 ng/mL; p < 0.001), sE-selectin (70.4 +/- 20.2 ng/mL vs 48.5 +/- 25.6 ng/mL; p = 0.005), sP-selectin (228.2 +/- 88.6 ng/mL vs 123.1 +/- 45.3 ng/mL; p < 0.001) and positive acute phase proteins ORM (0.82 +/- 0.16 g/L vs 0.64 +/- 0.20 g/L; p = 0.005), FBG (3.42 +/- 0.54 g/L vs 2.74 +/- 0.57 g/L; p = 0.037) and PAI-1 Ag (97.9 +/- 40.6 ng/mL vs 56.4 +/- 25.6 ng/mL; p < 0.05), and a decrease of negative acute phase protein TRF (2.14 +/- 0.40 g/L vs 2.77 +/- 0.45 g/L; p < 0.001) compared to the results in overweight non-hyperlipidemic controls. CONCLUSIONS: It is suggested that overweight adults have an increase of inflammatory response dependent on hyperlipidemia. It was apparent from the elevation of sE--selectin, sP--selectin and sICAM-1 and from an increase of systemic inflammatory response according to the increase of "positive" acute phase proteins (APRs) and the decrease of "negative" APR protein levels in these patients.

Acute-Phase Proteins↗

Interventional treatment of multiple vascular involvement in young male with heterozygous familial hypercholesterolemia.

We report a case of 31 year old man with heterozygous familial hypercholesterolemia and excessive tobacco use leading to acute myocardial infarction as the first manifestation of premature atherosclerosis. The patvent was treated by primary PTCA of occluded first marginal artery and at this time an attempt of recanalisation of occluded LAD was unsuccessful. The patient was referred for mini coronary bypass graft of the LIMA to LAD. During evaluation of carotid arteries we found a significant stenosis of the left internal carotid artery and occlusion of the left subclavian artery which made the use of LIMA unsuitable. Therefore, another attempt of PTCA of the occluded LAD was performed, this time with success. Hence PTA of the occluded subclavian artery was performed with good result. The patient was treated with the standard therapy of CAD and combined lipid lowering agents with significant reduction of plasma cholesterol. However, 2 years after the first MI, he suddenly died after swimming at the age of 31. In this patient the risk of premature CAD was increased by the presence of another powerful risk factor--the excessive tobacco use. Acute physical exercise probably acted as a trigger of acute coronary events at the time of both MI. Interventional methods were very effective in the treatment of multiple atherosclerotic lesions in this patient and provided significant relief of symptoms. Treatment of heterozygous FH is briefly discussed in this article.

Adult↗

Microvascular reactivity in patients with hypercholesterolemia: effect of lipid lowering treatment.

Impaired NO-dependent vasodilation of resistance vessels is an early marker of an increased risk of atherosclerosis; utility of the examination of microcirculation, however, is far less established. We have therefore tested the hypothesis that hypercholesterolemia is associated with an impaired microvascular reactivity and that this defect is at least partially reversible by lipid-lowering treatment. Twenty-seven otherwise healthy patients with severe hypercholesterolemia (HLP) were examined at rest and then after 10 weeks of atorvastatin treatment (20 mg/day). Skin microvascular reactivity (MVR) was examined by laser-Doppler flowmetry. Baseline MVR values of the studied group were compared to healthy control subjects, HLP patients with coronary artery disease (CAD) and diabetic patients with and without diabetic retinopathy. MVR was normal in HLP subjects without CAD. On the contrary, MVR was impaired in HLP patients with CAD. There was no effect of atorvastatin on MVR, despite the profound reduction of serum lipids. MVR values did not correlate with cholesterol levels. In diabetic subjects, the MVR was substantially impaired only in patients with retinopathy. In the subjects without retinopathy, MVR was either normal (type I diabetes) or moderately impaired (type II diabetes). MVR was thus normal in HLP patients without manifest vascular disease and was not influenced by lipid lowering therapy. Impairment in the MVR was only evident in subjects with HLP and severe CAD. These results suggest that microcirculation is not involved in the early vascular dysfunction induced by HLP and that MVR rather reflects changes which appear later in the course of the atherosclerotic disease.

Adult↗

Familial dysbetalipoproteinemia in three patients with apoE 2*(Arg136-->Cys) gene variant.

Apolipoprotein E (apoE) is a polymorphic protein which occurs in three common isoforms and more than 25 rare variants. Some of the rare apoE variants have been implicated in a dominant mode of inheritance of familial dysbetalipoproteinemia (FD). We have identified three unrelated apoE 2*(Arg136-->Cys) carriers with FD. This finding supports the notion that although apoE 2*(Arg136-->Cys) mutation is perhaps not sufficient to cause FD itself, the presence of other genetic and/or environmental factors can lead to the phenotypic expression of the disease in the carriers.

Aged↗

[Indirect relation between intimo-medial thickness of the carotid artery and vasodilation of the popliteal artery].

BACKGROUND: Intima-media thickness of the common carotid artery (IMT ACC) and flow-mediated vasodilatation (FMD) of the brachial artery is considered an early marker of atherosclerosis. This study was undertaken to elucidate whether endothelial dysfunction in the popliteal artery, pronoun to atherosclerosis, is related to IMT ACC. METHODS AND RESULTS: Twenty-nine control subjects, 29 asymptomatic patients with hyperlipoproteinemia (without therapy) and 26 patients with coronary artery disease were examined. Using ultrasound with a linear-array probe (7.5 MHz), we measured IMT ACC and diameter of the popliteal artery (PA) at rest and during reactive hyperaemia after release of 5-minute arterial occlusion. In control subjects we found thicker IMT ACC and greater FMD than did the patients (p<0.001, ANOVA test). A significant negative correlation between the IMT ACC and percent FMD was found in all of the subjects (p<0.001). On multiple regression analysis, percent FMD showed a significant negative correlation with the IMT ACC, total cholesterol, triacylglyceroles, body mass index, age, and diastolic blood pressure. CONCLUSION: We found significant negative correlation between IMT common carotid artery and FMD popliteal artery.

Adult↗

[Dilatation of the popliteal artery in hyperemia and intimal-medial thickness of the carotid artery in hyperlipoproteinemia, ischemic heart disease and in healthy individuals].

Non-invasive measurement of the intima-media thickness (IMT) of the carotid artery and flow-mediated dilatation (FMD) of the brachial artery are increasingly used as surrogate markers of vascular disease. Using ultrasound, we measured the diameter of the popliteal artery at rest and during reactive hyperaemia after release of 5-minute arterial occlusion. We also measured IMT of the common carotid artery. In 29 control subjects (average age 35 years) we demonstrated an increase in the diameter by 6.0 +/- 3.3% (p < 0.05), in 29 asymptomatic patients with hyperlipidemia (without therapy, average age 46 years) only by 0.9 +/- 3.0% and in patients with coronary heart disease (average age 50 years) only by 0.2 +/- 2.7%. The difference between patients and control subjects was highly significant (p < 0.001). IMT was 0.58 +/- 0.10 mm, 0.78 +/- 0.17 mm and 1.03 +/- 0.25 mm respectively (p < 0.001). We conclude that in patients FMD of the popliteal artery is smaller and IMT of the common carotid artery is thicker than in controls.

Adult↗

[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↗

Both fenofibrate and atorvastatin improve vascular reactivity in combined hyperlipidaemia (fenofibrate versus atorvastatin trial--FAT).

OBJECTIVE: It has been repeatedly proven that statins improve endothelial function in isolated hypercholesterolaemia but there is far less evidence in the case of combined hyperlipidaemia. Studies assessing the effects of fibrates on endothelium have been neglected. Therefore, we conducted a trial in which the effects of fenofibrate and atorvastatin monotherapy on both endothelium-dependent vascular reactivity and biochemical parameters were compared in patients with combined hyperlipidaemia. METHODS: 29 otherwise healthy males (aged 47.4+/-7.8 years) with combined hyperlipidaemia (total cholesterol 7.55+/-1.20 mmol/l, triglycerides 5.41+/-4.54 mmol/l) were included into the randomised, single-blind, cross-over study to receive either 200 mg of micronised fenofibrate or 10 mg of atorvastatin daily--each of the drugs for a period of 10 weeks. Analysed biochemical parameters were as follows: serum total-, LDL- and HDL-cholesterol, apolipoproteins A-I and B, triglycerides, fibrinogen, uric acid, C-reactive protein (CRP), insulin, and homocysteine. Endothelial function was investigated by duplex Doppler ultrasonography at the brachial artery. Two indices of endothelial-dependent postischaemic changes were used - the recently introduced index of peak blood flow (PBF) representing the level of reactive hyperaemia and traditional flow-mediated dilatation (FMD). RESULTS: We observed a small improvement in FMD after both fenofibrate and atorvastatin (from 2.26% to 2.98% and 2.87%, respectively; NS). PBF increased from 448 ml/min to 536 ml/min after fenofibrate (P=0.04) and to 570 ml/min after atorvastatin (P=0.03). The effects of both fenofibrate and atorvastatin on endothelial function did not differ significantly (P-values of 0.82 and 0.47 for FMD and PBF, respectively). Significant correlations (P<0.01) between the changes of vascular reactivity and biochemical indices were found between FMD and CRP (r=-0.60) and between both FMD and PBF, and insulinaemia (r=-0.48 and -0.56, respectively) only during treatment with fenofibrate. CONCLUSIONS: Both fenofibrate and atorvastatin significantly improved endothelium-dependent vascular reactivity without mutual difference. The PBF was superior to FMD for the detection of this improvement. The beneficial effect of both drugs did not correlate with the change of lipid profile during therapy. The improvement of vascular reactivity during treatment with fenofibrate (opposed to atorvastatin) was related to the reduction of indirect marker of chronic vessel wall inflammation and of insulin resistance. The PBF was more reproducible than FMD because of considerably lower intra-subject variability.

Adult↗

Folate supplementation prevents plasma homocysteine increase after fenofibrate therapy.

BACKGROUND: Homocysteine is associated with an increased risk of atherosclerosis. The administration of fibrates has been reported to significantly increase plasma homocysteine levels, a potentially adverse effect of fibrates. We investigated the hypothesis that concomitant treatment with fenofibrate and folic acid leads to a smaller increase in plasma total homocysteine levels than treatment with fenofibrate alone. METHODS: A randomized, open-label study compared the effect of micronized fenofibrate (200 mg daily) alone versus fenofibrate plus folic acid (10 mg every other day) on plasma homocysteine levels. Twenty-two patients with mixed hyperlipidemia participated. The 9-wk treatment period was preceded by a 4-wk wash-out period without hypolipidemic drugs. RESULTS: In patients treated with fenofibrate only, plasma homocysteine levels increased by 6.85 +/- 5.23 micromol/L (from 12.27 +/- 3.15 to 19.13 +/- 7.20 micromol/L); in patients treated with fenofibrate and folic acid, plasma homocysteine levels increased by 2.01 +/- 2.88 micromol/L (from 10.14 +/- 2.32 to 12.15 +/- 3.08 micromol/L). The difference in the homocysteine increase between the two groups was statistically significant at P = 0.014. CONCLUSIONS: Folic acid supplementation in patients treated with fenofibrate significantly reduced the increase in plasma homocysteine levels. More studies are needed to clarify whether amelioration of this side effect increases the clinical benefit of fibrates.

Arteriosclerosis↗

Flow-dependent vasomotor dysfunction of the popliteal artery related to common carotid artery intima-media thickness.

This study was designed to assess a possible correlation between flow-mediated endothelium-dependent vasodilation in the popliteal artery and the intima-media thickness of the common carotid artery. Impaired vasodilation is one of early markers of atherosclerosis that has not been studied on the popliteal artery. An increase in intima-media thickness of the common carotid artery is also considered to be an indication of early stages of atherosclerosis. With use of ultrasound, the diameter of the popliteal artery was measured at rest and during reactive hyperemia after 5-minute arterial occlusion. Subsequently, the intima-media thickness was measured in left common carotid arteries in 27 patients with hyperlipidemia, in 10 patients with confirmed coronary artery disease, and in 20 healthy individuals. In healthy individuals, popliteal artery diameter increased by mean of 6.6 +/- 3.5% (p < 0.01) in relation to hyperemia. In patients with hyperlipidemia before therapy and in patients with coronary disease, no increase in diameter occurred (mean, 0.44% and -1.6%, respectively). The difference between healthy individuals and patients was statistically significant at p < 0.001. The popliteal artery seems to respond similarly to the brachial artery. When comparing the change in popliteal artery diameter and intima-media thickness of common carotid arteries, a strong negative correlation (r = -0.5713, p < 0.001) was observed in all subjects.

Adult↗

Effects of transdermal application of 7-oxo-DHEA on the levels of steroid hormones, gonadotropins and lipids in healthy men.

The aim of this study was to investigate the effect of 7-oxo-DHEA (dehydroepiandrosterone) on the serum levels of steroid sexual hormones, gonadotropins, lipids and lipoproteins in men. 7-oxo-DHEA was applied onto the skin as a gel to 10 volunteers aged 27 to 72 years for 5 consecutive days. The single dose contained 25 mg 7-oxo-DHEA. Serum concentrations of testosterone, estradiol, cortisol, androstenedione, luteinizing hormone (LH), follicle-stimulating hormone (FSH), sex hormone binding globulin (SHBG), total cholesterol, HDL- and LDL-cholesterol, triglycerides, apolipoprotein A-I and B and lipoprotein(a) were measured before the beginning and shortly after the end of the steroid application. After the treatment, we noted the following significant changes: a decline of testosterone and estradiol levels, increase of LH, HDL-cholesterol and apolipoprotein A-I levels. The decrease of total cholesterol levels was of the borderline significance. A slight but significant increase was found in apolipoprotein B and lipoprotein(a). The most expressive was the fall of the atherogenic index. We suggest that the gel containing 7-oxo-DHEA might be a suitable drug for improving the composition of the steroid and lipid parameters in elderly men.

Administration, Cutaneous↗