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T Stulc

Publications and source records attributed to T Stulc.

13 recordsLinked to original sources
PubMed2005

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↗
PubMed2005

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↗
PubMed2003

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↗
PubMed2003

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↗
PubMed2001

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↗
PubMed2001

Cholesterol lowering and the vessel wall: new insights and future perspectives.

The basis for most acute coronary events is either rupture or fissuring of unstable atherosclerotic plaques with subsequent thrombosis leading to coronary artery occlusion. The development of atherosclerotic plaques takes several decades, but the mechanical features determining its stability and the risk of rupture can change very rapidly depending on a number of internal factors. Unstable plaques have a large lipid core, a thin overlying fibrous cap and an abundance of inflammatory cells. The most important factor determining the plaque stability is the plasma level of atherogenic LDL particles. Increased levels of these particles cause endothelial dysfunction with impaired vasodilatation capacity and prevalence of vasoconstriction, maintain inflammatory infiltration of the plaque, impair the strength of the fibrous cap and facilitate aggregation and coagulation. Effective lowering of plasma cholesterol by pharmacological and non-pharmacological means can revert most of these processes and increase the plaque's mechanical stability within several hours to days. Lipid lowering therapy can therefore decrease the risk of acute coronary events within a very short space of time. Thus a radical decrease in lipid levels, along with modification of other risk factors, may become the cornerstone for treatment of acute coronary syndromes, in addition to being an effective treatment in primary and secondary prevention of coronary heart disease (CHD).

Anticholesteremic Agents↗
PubMed2000

[Fenofibrate 250 SR Pharmavit in patients with mixed hyperlipoproteinemia. Results of a study of 189 patients from 13 centers in the Czech Republic].

BACKGROUND: Hyperlipoproteinemia represents one of the major risk factors in the early atherosclerosis manifestation, namely in the ischaemic heart disease. In patients after the myocardial infarction, mixed hyperlipoproteinemia becomes the most frequently diagnosed impairment of the lipid metabolism. In the therapy, fibrates begin to play an important role. A new remedy containing micronised fenofibrate (Fenofibrate 250 SR Pharmavit) was recently registered for the Czech market. The aim of our study was to test its effects in almost 200 patients with mixed hyperlipoproteinemia. METHODS AND RESULTS: Into statistical analysis of the treatment effectiveness 187 persons (115 males, 72 females) were included. Other characteristics of the studied group (mean +/- SD): age 54.0 +/- 10.7 years, stature 172.0 +/- 8.7 cm, weight, BMI 28.0 +/- 3.1. Prevalence of risk factors and clinical manifestations of the atherosclerosis: ICHS 18.2%, myocardial infarction 7.5%, ICHDK 4.3%, CMP 5.3%, smoking 27.8%, arterial hypertension 63.6%, diabetes mellitus 17.6%, positive family history in ICHS 50.3%. 44.9% persons had been treated with hypolipidemics. Basic parameters of the lipid metabolism, cholesterol, LDL and HDL cholesterol and triglycerides were studied. Plasma levels of uric acid, fibrinogen, glucose and other biochemical parameters were also used to monitor the safeness of the treatment. Cholesterol concentration (7.05 +/- 0.91 mmol/l) decreased (6.14 +/- 0.89 mmol/l) almost by 15%. Triglyceride concentration decrease (from 4.43 +/- 1.84 mmol/l to 2.64 +/- 1.34 mmol/l) was more intensive (41%). HDL-cholesterol increased by almost 15%, while LDL-cholesterol decreased by 12%. Statistically significantly decreased level of the uric acid (12%), fibrinogene decrease (8.4%) reached only marginal significance. Treatment was well tolerated, only in one patient it was necessary to cut it prematurely. CONCLUSIONS: According clinical tests which included almost 200 patients with mixed hyperlipoproteinemia, Fenofibrate 250 SR Pharmavit stands for an effective and well tolerated hypolipidemics.

Female↗
PubMed2000

[Hyperlipoproteinemia, the Apo-E genotype and bone density].

BACKGROUND: Both atherosclerosis and osteoporosis often appear together, especially in the elderly; usually they are regarded as independent entities. Only recently epidemiological evidence occurred suggesting possible associations between these diseases. Several groups of factors (genetic, hormonal and biochemical) have been studied to account for this association. Among the genetic factors, apolipoprotein E has been studied most extensively; some results indicate that carriers of E4 allele are at increased risk of osteoporosis. A possible influence of plasma lipoproteins and of tissue ischaemia on bone metabolism has also been studied. AIM OF THE STUDY: To test the hypothesis that there is an association between apolipoprotein E, plasma lipid concentrations and bone mineral density. METHODS: We examined 18 apolipoprotein E2/2 and E4/4 homozygotes and 130 postmenopausal women. Bone mineral density and plasma triglycerides, total and HDL cholesterol were determined in both groups; in apolipoprotein E homozygotes biochemical markers of bone turnover were also measured. RESULTS: No significant differences in bone mineral density and bone remodelling were found between the E2/2 and E4/4 homozygotes. A negative correlation between lumbar spine bone mineral density and cholesterol and triglyceride concentrations (r = 0.20-0.39) was observed both in postmenopausal women and apolipoprotein E homozygotes. CONCLUSION: We didn't observe any association of apolipoprotein E genotype with bone mineral density and biochemical markers of bone metabolism. A negative association between plasma lipid concentrations and bone mineral density supports the hypothesis of harmful effect of hyperlipidaemia on bone metabolism.

Alleles↗
PubMed2000

Age and residual cholesterol efflux affect HDL cholesterol levels and coronary artery disease in ABCA1 heterozygotes.

We and others have recently identified mutations in the ABCA1 gene as the underlying cause of Tangier disease (TD) and of a dominantly inherited form of familial hypoalphalipoproteinemia (FHA) associated with reduced cholesterol efflux. We have now identified 13 ABCA1 mutations in 11 families (five TD, six FHA) and have examined the phenotypes of 77 individuals heterozygous for mutations in the ABCA1 gene. ABCA1 heterozygotes have decreased HDL cholesterol (HDL-C) and increased triglycerides. Age is an important modifier of the phenotype in heterozygotes, with a higher proportion of heterozygotes aged 30-70 years having HDL-C greater than the fifth percentile for age and sex compared with carriers less than 30 years of age. Levels of cholesterol efflux are highly correlated with HDL-C levels, accounting for 82% of its variation. Each 8% change in ABCA1-mediated efflux is predicted to be associated with a 0.1 mmol/l change in HDL-C. ABCA1 heterozygotes display a greater than threefold increase in the frequency of coronary artery disease (CAD), with earlier onset than unaffected family members. CAD is more frequent in those heterozygotes with lower cholesterol efflux values. These data provide direct evidence that impairment of cholesterol efflux and consequently reverse cholesterol transport is associated with reduced plasma HDL-C levels and increased risk of CAD.

ATP Binding Cassette Transporter 1↗
PubMed2000

Bone mineral density in patients with apolipoprotein E type 2/2 and 4/4 genotype.

The peak bone mass and the rate of bone loss are in part genetically determined. It has been suggested that bone mineral density (BMD) may be related to allelic variation in the apolipoprotein E (ApoE) gene locus. ApoE is important in the receptor-mediated clearance of chylomicron particles from the plasma, Apo E4 having the highest and Apo E2 the lowest receptor affinity. Chylomicrons are the main carrier of vitamin K in the plasma; vitamin K plays an important role in the carboxylation of osteocalcin. We have tested the hypothesis that persons with E4 variant would have lower BMD and increased bone turnover than those with E2 variant. A total of 18 ApoE 2/2 and ApoE 4/4 homozygotes were selected from 873 patients who were examined for the ApoE genotype. BMD in lumbar vertebral, femoral neck and distal forearm was measured and plasma concentrations of osteocalcin and C-terminal fragments of collagen (CTx) were determined. BMD values (expressed as T-score) at the three specified sites were -0.12+/-1.72, -0.52+/-1.32 and -0.52+/-0.81 in ApoE 2/2 group and -0.24+/-1.22, 0.00+/-0.84 and -0.17+/-1.07 in the ApoE 4/4 group. Plasma osteocalcin and CTx were within normal limits in both groups. In conclusion, we did not observe any association of ApoE genotype with BMD and biochemical markers of bone metabolism in ApoE 2/2 and ApoE 4/4 homozygotes.

Adult↗
PubMed1997

Immunocytochemical detection of estrogen receptors in bone cells using flow cytometry.

A sensitive method for immunocytochemical detection of estrogen receptors using flow cytometry is reported. Using this method, estrogen receptors were detected in several osteoblastic cell lines with established expression of estrogen receptors, and for the first time, estrogen receptors were also demonstrated in murine fibroblasts and in human primary marrow stromal cells. The distribution of estrogen receptors within all cell lines was unimodal. The method enables for studies of estrogen receptors in the cell types which express low to moderate levels of the receptors, for studies of heterogeneity of the receptors' expression and for simultaneous detection of several parameters on a single-cell level.

Animals↗
PubMed1997

Comparative study on the effect of calcium channel blockers on basal and parathyroid hormone-induced bone resorption in vitro.

A number of clinical and experimental studies suggest that the effects of calcium channel blockers are not limited to the cardiovascular system but might also involve skeletal calcium metabolism due to the presence of L-type calcium channels in osteoblastic cells. We therefore investigated the influence of calcium channel blockers of the dihydropyridine type (nifedipine, amlodipine) as well as of the phenylalkylamine type (verapamil, gallopamil) on basal and parathyroid hormone-induced bone resorption utilizing organ-cultured neonatal mouse calvaria. Only at 10(-4) M, amlodipine, verapamil and gallopamil reduced basal and parathyroid hormone-induced resorption In contrast, nifedipine, between 10(-5)-10(-4) M, exhibited a dose-dependent inhibitory effect on parathyroid hormone-related bone resorption by up to 50%. When calvariae were cultured for 48 hr in the presence of inhibitory concentrations of the calcium channel blockers and then stimulated with parathyroid hormone, only parietal bones pretreated with nifedipine remained completely responsive to the bone resorbing action of the hormone.

Amlodipine↗