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Biomedical subjects

Richard Ceska

Publications and source records attributed to Richard Ceska.

15 recordsLinked to original sources
PubMed2006

Detection of variability in apo(a) gene transcription regulatory sequences using the DGGE method.

BACKGROUND: Increased lipoprotein(a), Lp(a), concentration is an independent risk factor for premature atherosclerosis. Apolipoprotein(a), apo(a), determines properties of the lipoprotein and its production rate is the limiting step in Lp(a) particle formation. METHODS: Subjects covering the whole range of Lp(a) concentration were separated into quintiles. A randomly chosen sample from each quintile was derived, there being a total number of 713 individuals. The DGGE method was used to scan the known transcription regulatory regions of apo(a) gene (promoter; DHII and DHIII enhancers) for variability and its distribution across quintiles. RESULTS: Besides 5 previously reported nucleotide substitutions (+121 G>A; +93 C>T; -1712 G>T; -1617 C>A; -1230 A>G) 16 unreported rare sequence variants were detected. All polymorphic variants were distributed throughout the quintiles with several significant differences. The novel +62 C variant was found only among individuals with Lp(a) levels over 16 mg/dl. CONCLUSION: The apo(a) gene transcription regulatory regions were not revealed to be extremely polymorphic. However, we should consider a combined effect of all polymorphic sites from the whole apo(a) gene locus, including the apo(a) gene length polymorphism, when dealing with high population variability of Lp(a) levels.

Apoprotein(a)↗
PubMed2005

Cholesterol-lowering therapy evokes time-limited changes in serotonergic transmission.

A number of studies have reported an increased risk for violent deaths and depression in subjects with reduced serum cholesterol concentrations. Links with hypothesized impairment of serotonin neurotransmission have not been satisfactorily tested. In this investigation, the serum and membrane cholesterol, microviscosity of erythrocyte membranes, platelet serotonin uptake, and clinical parameters were determined during pharmacotherapy of 17 hypercholesterolemic patients. A significant decrease in serum cholesterol and a nonsignificant decrease in membrane cholesterol concentration were found after 2 months of simvastatin therapy. Serotonin transporter (SERT) activity was significantly increased following 1 month of simvastatin; the tendency to decrease the initial increase in SERT activity was evident following 2 months of therapy. Both membrane cholesterol and SERT activity returned to pre-treatment levels after more than 1 year of therapy. Microviscosity of plasma membranes, impulsivity, empathy, adventure, sensation seeking, and depressed mood were not markedly changed. These data indicate that long-term therapy has different effects on serotonin transmission from short-term (1- to 2-month) therapy. A significant increase in SERT activity was detected only during the first month of simvastatin therapy. This finding suggests that within this period some patients could be vulnerable to depression, violence, or suicide.

Adult↗
PubMed2004

Effect of simvastatin and fenofibrate on endothelium in Type 2 diabetes.

Statins and fibrates influence endothelial activity and consequently atherogenesis but the mechanisms are not well understood. Twenty Type 2 diabetic patients with dyslipidemia were treated 3 months with simvastatin (20 mg daily) and then 3 months with fenofibrate (200 mg daily) with 2 months of wash-out between the two treatments. Laboratory parameters of oxidative stress, fibrinolysis and endothelial function were evaluated before and at the end of each treatment period. The significant decrease in serum total and LDL-cholesterol concentrations (P<0.0001) caused by simvastatin was associated with an increase in serum N-acetyl-beta-glucosaminidase activity (P<0.001), ascorbic acid (P<0.001), plasminogen activator inhibitor (PAI-1) (P<0.01), vonWillebrand factor (P<0.05), E-selectin (P<0.01) and vascular endothelial growth factor (P<0.05) concentrations and with a decrease in plasma glutathione (P<0.01) levels. Fenofibrate caused a significant decrease in serum triglyceride concentration (P<0.0001) associated with a decrease in plasma malondialdehyde (P<0.001) and an increase in plasma PAI-1 (P<0.05) and P-selectin (P<0.05) concentrations. We conclude that simvastatin and fenofibrate interact, by different mechanisms, with oxidative stress, a key factor in the modification of fibrinolysis and endothelial function in Type 2 diabetes.

Acetylglucosaminidase↗
PubMed2004

New strategies in the treatment of dyslipidemia: do we know how?

The treatment of dyslipidemia is beyond doubt one of the cornerstones of cardiovascular prevention. If we want to touch and comment on at least the principal news in this broad field, we must simplify and pay attention to only a few selected areas. The focus of this article is on hypercholesterolemia and the treatment options for elevated low-density lipoprotein (LDL)-cholesterol; it also addresses the questions of low high-density lipoprotein (HDL)-cholesterol levels and the treatment of dyslipidemia of the metabolic syndrome. In particular, statins have had accumulation of new evidence resulting in novel indications and new target groups. Modern, even more potent drugs lowering total and LDL-cholesterol levels are available (new statins, e.g., rosuvastatin, pitavastatin, cholesterol absorption inhibitor ezetimibe) More and more attention of the medical public is being paid to dyslipidemia of the metabolic syndrome (so-called lipid triad), which seems to be the greatest rival of LDL-cholesterol among lipid risk factors for cardiovascular disease. In the treatment of this dyslipidemia especially the nuclear peroxisome proliferator-activated receptor (PPAR) agonists play an important role. In particular fibrates but also glithasones are noteworthy in this respect. There are fewer data for fibrates than for statins, but nevertheless evidence documenting benefit of this therapy is growing. A statin and fibrate combination is a promising future approach not only to the treatment of metabolic syndrome. Moreover, niacin, particularly in combination with a statin, might experience a renaissance. HDL-cholesterol level modification attracts more and more discussions; on the horizon there are new therapies of low HDL, for example, cholesterol-ester transfer protein inhibitors, which have been shown to have a potency for increasing HDL by more than 50%.

Clinical Trials as Topic↗
PubMed2003

Effect of atorvastatin and fenofibrate on autonomic tone in subjects with combined hyperlipidemia.

This randomized open-label trial investigated whether autonomic cardiovascular control is altered in middle-aged men with combined hyperlipidemia and whether such alterations are affected by short-term, lipid-lowering therapy with atorvastatin and/or fenofibrate. Compared with normolipidemic subjects, untreated subjects with combined hyperlipidemia had several abnormalities of autonomic tone, indicating increased sympathetic tone and decreased baroreflex sensitivity. The alterations in autonomic cardiovascular control were partially reversible by each of the lipid-lowering drugs.

Adult↗
PubMed2003

Effect of folic acid on fenofibrate-induced elevation of homocysteine and cysteine.

BACKGROUND: An elevated total plasma homocysteine (tHcy) level is considered to be an independent risk factor for atherosclerosis. It has been reported that lipid-lowering therapy with fibric acid derivatives (fibrates) increases tHcy and total plasma cysteine (tCys) levels. The aim of this study was to determine whether therapy with folic acid, a potent tHcy-lowering agent, could modify the fenofibrate-induced elevation of plasma aminothiols. METHODS: Patients with combined hyperlipidemia (n = 37) were randomized to receive 9 weeks of treatment with micronized fenofibrate 200 mg/day (F group) or fenofibrate 200 mg/day plus folic acid 10 mg/every other day (F+F group). tCys and tHcy levels were determined before and after the therapy with high performance liquid chromatography. RESULTS: The tHcy level increased significantly in the F group by 51.3% and in the F+F group by 14.6% (between-group difference P =.001). Total plasma cysteine (tCys) increased similarly after both treatments (P =.72). The serum creatinine level increased in the F group by 20.7% and in F+F group only by 9.8% (P =.04). The increase of tHcy level in F group correlated with an increase of tCys and creatinine levels (r = 0.74 and 0.64, respectively). The effects on the lipid profile did not differ by treatment group. CONCLUSIONS: Folic acid effectively reduces the fenofibrate-induced elevation of tHcy and creatinine, but it does not affect the elevation of the tCys. Folic acid has neutral effect on the lipid-lowering action of fenofibrate. Clinical efficacy of fenofibrate might be improved by folic acid coadministration.

Cholesterol↗
PubMed2003

Increased levels of pregnancy-associated plasma protein-A in patients with hypercholesterolemia: the effect of atorvastatin treatment.

BACKGROUND: Serum levels of pregnancy-associated plasma protein-A (PAPP-A) have recently been linked to plaque instability and are increased in acute coronary syndromes. The relation between PAPP-A levels and coronary risk factors, namely blood lipids, has not been studied to date. We have therefore investigated whether serum PAPP-A levels are increased in asymptomatic hypercholesterolemic subjects and whether PAPP-A levels are influenced by atorvastatin therapy. METHODS: We examined 27 subjects with isolated hypercholesterolemia free of manifest vascular disease and 29 age-matched healthy control subjects. Patients were examined at baseline and after 10 weeks of atorvastatin treatment (20 mg/d). RESULTS: In untreated hypercholesterolemic subjects, PAPP-A levels were significantly higher than in control subjects (8.02 +/- 1.86 mU/L vs 6.50 +/- 2.54 mU/L, P =.018). There was no correlation between PAPP-A levels and serum lipid levels. Atorvastatin treatment reduced total and LDL-cholesterol by 31% and 40%, respectively. Despite this profound lipid lowering, there was no significant change in the serum PAPP-A levels. CONCLUSIONS: PAPP-A levels are elevated in hypercholesterolemic subjects without clinical signs of atherosclerosis. PAPP-A may therefore not only reflect plaque instability but also serve as a marker of total atherosclerotic burden in asymptomatic subjects with hyperlipidemia. However, PAPP-A levels are not influenced by atorvastatin treatment.

Anticholesteremic Agents↗
PubMed2002

Comparison of the effects of atorvastatin or fenofibrate on nonlipid biochemical risk factors and the LDL particle size in subjects with combined hyperlipidemia.

BACKGROUND: Combined hyperlipidemia (CH) is an increasingly prevalent risk factor for premature heart disease, and its treatment is troublesome. The aim of this study was to compare the effects of atorvastatin and fenofibrate on nonlipid biochemical risk factors and the low-density lipoprotein (LDL) particle size in subjects with CH. METHODS: Twenty-nine middle-aged men with CH were randomly assigned to open-label therapy with atorvastatin (10 mg daily) or micronized fenofibrate (200 mg daily); they were sequentially treated with both drugs, with crossover of medication after 10 weeks. RESULTS: Atorvastatin was more efficient in the reduction of total cholesterol, whereas fenofibrate was more efficient in the reduction of triglycerides. Only atorvastatin led to a significant reduction of LDL cholesterol and apolipoprotein B. Only fenofibrate increased high-density lipoprotein cholesterol. Neither drug influenced lipoprotein(a). Mean LDL particle size increased both after fenofibrate (3.08%) and atorvastatin (1.77%). Fenofibrate increased serum homocysteine (HCY) by 36.5%. Atorvastatin had no effect on HCY. Only atorvastatin increased fibrinogen by 17.4%. Only fenofibrate reduced C-reactive protein by 51.7%. Neither drug influenced HOMA (homeostasis model assessment) index of insulin resistance. The plasma level of thiobarbituric acid reactive substances, an index of oxidative stress, decreased after both treatments. CONCLUSIONS: Both atorvastatin and fenofibrate had similar beneficial effects on LDL particle size and on oxidative stress. The effects of both drugs on other parameters such as triglycerides, total and high-density lipoprotein cholesterol, fibrinogen, or HCY differed significantly. These differences, together with the risk profile of a patient, should be considered during selection of a particular lipid-lowering modality.

Apolipoproteins B↗
PubMed2002

Nitroglycerin induced syncope occurs in subjects with delayed phase shift of baroreflex action.

Nitroglycerin (NTG) administration occasionally leads to syncope due to severe hypotension and bradycardia. This reaction resembles neurocardiogenic syncope but it may occur when the patient is in the supine position. To address the possible role of prevailing autonomic tone and baroreflex control in precipitation of NTG induced syncope, continuous noninvasive blood pressure and an ECG were taken shortly before NTG application in the supine position. Frequency-domain measures of heart rate variability (HRV) and noninvasive indices of baroreflex were compared between subjects who did (n = 6) and did not (n = 41) develop syncope after NTG. Both groups differed only in the phase shift (P(CR)) between oscillations of blood pressure and heart rate during controlled respiration (0.1 Hz). P(CR) was significantly delayed in subjects who developed syncope than in controls (- 99.3+/-14.1 vs -65.5+/-27.0 degrees, P = 0.002). Thus, subjects with prolonged P(CR) are prone to NTG induced syncope because of increased lagging and, consequently, less stable baroreflex control.

Adult↗