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Biomedical subjects

F Simko

Publications and source records attributed to F Simko.

At least 19 recordsLinked to original sources
PubMed2001

Resistance to activated protein C--frequent etiologic factor for venous thrombosis.

The discovery of the resistance to activated protein C (APCR) has provoked a new insight into the etiopathogenesis of venous and arterial thrombosis. APCR is determined in 95% genetically by point mutation in the gene for factor V resulting in substitution of arginine in the position 506 by glutamine. This change makes the activated form of factor V (factor Va) resistant to the cleavage by protein C in the place, where the cleavage takes place most quickly under normal conditions. The mutant factor V is known as factor V Leiden. Factor V Leiden preserves its procoagulation activity for a longer period, resulting thus into thrombophilia with all its negative consequences. The inherited deficiencies of antithrombin III, protein C and protein S occur in 10% of patients suffering from venous thrombosis, whereas factor V Leiden is present in as many as 20 to 60%. Thus, it seems that factor V Leiden is the most important inherited risk factor of venous thrombosis. The results of several trials did not indicate the participation of APCR in the development of myocardial infarction. On the other hand, APCR seems to be a risk factor of cerebrovascular accidents, especially of stroke and transitory brain ischemia. Factor V Leiden is an important risk factor of abortions, especially those occurring in the second trimester of pregnancy. According to recent results, factor V Leiden is considered to play a role in the pathogenesis of venous and arterial thromboses in children. The significant risk potential of factor V Leiden with respect to venous thrombosis development and relatively simple diagnosis of this mutation predispose the investigation of this disorder to become the screening method in indicated groups of patients. The investigation of APCR is recommended in all patients with either first or reoccurring attacks of venous thrombosis or thromboembolism, in patients with positive family history of thrombosis and thromboembolism and in women with repeated abortions, particularly in the second trimester of pregnancy. The investigation of APCR in selected groups of patients and early prophylactic anticoagulation therapy may be important in thrombosis prevention in situations with an increased thrombotic potential. (Tab. 1, Ref. 78.)

Activated Protein C Resistance↗
PubMed2000

Regression of chronic L -NAME-treatment-induced left ventricular hypertrophy: effect of captopril.

Long-term administration of N(G)-nitro- L -arginine methyl ester (L -NAME) induces development of NO-deficient hypertension and left ventricular (LV) hypertrophy. In this work, we examined the effect of spontaneous and captopril-induced recovery on LV hypertrophy and protein composition in rats with developed L -NAME-induced hypertension. Four groups of rats were investigated: control L -NAME 40 mg/kg/day for 4 weeks (L -NAME) L -NAME 40 mg/kg/day for 4 weeks followed by 3-week spontaneous recovery (L -NAME+R) L -NAME 40 mg/kg/day for 4 weeks followed by 3 weeks of captopril treatment at a dose of 100 mg/kg/day (L -NAME+C). LV hypertrophy in the L -NAME group was associated with an increase in content and concentration of left ventricular DNA and RNA, concentration of metabolic proteins (MP) and soluble collagenous proteins (SCP). Spontaneous recovery period reduced the hypertension, without regression of LV hypertrophy. Left ventricular DNA and RNA content were increased in the L -NAME+R group. In this group, concentrations of MP, contractile proteins (CP), and collagenous proteins did not differ from those in the L -NAME group. Captopril treatment caused total regression of hypertension and LV hypertrophy and decreased both content and concentration of DNA and RNA, as well as the contents of MP, CP and SCP v the L -NAME group. However, after captopril treatment, concentration of collagenous and non-collagenous protein fractions remained increased v control. We conclude that spontaneous regression of L -NAME-induced hypertension is not associated with regression of LV hypertrophy. LV hypertrophy was regressed only in captopril-treated animals.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

Effect of angiotensin-converting enzyme inhibitors on non-diseased myocardium of experimental animals: potential clinical implications.

Angiotensin-converting enzyme (ACE) inhibitors protect the hearts of patients with different levels of cardiac disorder. The greatest benefit seems to be achieved in subjects with most severe heart failure. Moreover, ACE inhibition is protective also in patients without manifested heart failure but with severe systolic left ventricular dysfunction. Data are presented that ACE inhibitors can alter the composition of the myocardium also in control: healthy animals. In rats and rabbits with non-diseased heart, chronic ACE inhibition reduced fibrotic tissue concentration in the left ventricle. We speculate that if this were applied to humans, ACE inhibition may prove to be of potential benefit in subjects with normal systolic function but with a trend to left ventricular filling abnormalities caused by increased ventricular stiffness. In these patients reduction of myocardial fibrotic tissue might prevent deterioration of diastolic function.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

The potential role of nitric oxide in the hypertrophic growth of the left ventricle.

Left ventricular hypertrophy (LVH) is the result of interaction between a chronic hemodynamic overload and non-hemodynamic factors. There are several lines of evidence presented in this work suggesting that nitric oxide (NO) may participate in the hypertrophic growth of the myocardium. First, endothelial NO production was shown to be decreased in several types of hemodynamically overloaded circulation both in animals and humans. Second, compounds stimulating NO production were able to diminish the extent or modify the nature of LVH in some models of myocardial hypertrophic growth. Third, arterial hypertension can be induced by inhibition of nitric oxide synthase activity. This NO-deficient hypertension is associated with the development of concentric LVH, myocardial fibrosis and protein remodeling of the left ventricle. The mechanism of LVH development in NO-deficient hypertension is complex and involves decreased NO production and increased activation of the renin-angiotensin-aldosterone system. Cardiovascular protection via ACE inhibition in NO-deficient hypertension may be induced by mechanisms not involving an improvement of NO production. In conclusion, the hypertrophic growth of the LV appears to be the result of interaction of vasoconstrictive and growth stimulating effects of angiotensin II on the one hand and of vasodilating and antiproliferative effects of nitric oxide on the other.

Animals↗
PubMed2000

Passive smoking impairs endothelium-dependent relaxation of isolated rabbit arteries.

The aim of the present study was to examine the effect of prolonged passive smoking (lasting 3 weeks) on plasma catecholamine levels and reactivity of isolated rabbit arteries. Plasma noradrenaline, adrenaline and dopamine levels were determined radioenzymatically. Isolated rings of the thoracic aorta and carotid artery were suspended in organ chambers and connected to a force transducer for the recording of isometric tension. Plasma noradrenaline levels were found to be significantly elevated in rabbits subjected to passive smoking for 3 weeks. Plasma adrenaline and dopamine levels were not changed. Transmural nerve stimulation of arterial rings evoked frequency-dependent contractions. Prolonged passive smoking did not affect neurogenic contractions of the arteries tested. On the other hand, endothelium-dependent relaxations of phenylephrine-precontracted arteries were significantly impaired. Furthermore, hypertrophy of the left ventricle was observed. In conclusion, passive smoking impairs endothelium-dependent relaxations but not neurogenic contractions of systemic arteries. The impaired relaxations of arteries may be, at least in part, mediated through the degradation of released nitric oxide by superoxide anions derived from cigarette smoke.

Animals↗
PubMed1999

Captopril increased mitochondrial coenzyme Q10 level, improved respiratory chain function and energy production in the left ventricle in rabbits with smoke mitochondrial cardiomyopathy.

The aim of the study was to show whether the ACE inhibitor captopril is able to protect the heart against the deleterious effect of passive cigarette smoking on left ventricular mitochondria. Four groups of rabbits were investigated: control (C), passive smoking of three cigarettes twice daily/30 minutes (S), control + captopril (7.5 mg/kg body weight twice daily) (Cap), and smoking + captopril (SCap) as in group 2 and 3. Three weeks lasting passive smoking impaired oxidative phosphorylation, diminished cytochrome oxidase activity and increased the mitochondrial F1-ATPase protein concentration. Moreover, the level of coenzyme Q10 (CoQ10) and coenzyme Q9 were decreased. Simultaneous treatment with captopril prevented partly the decrease of CoQ10 level, deterioration of oxidative phosphorylation, diminution of cytochrome oxidase activity and enhancement of F1-ATPase level. We conclude that captopril protected the myocardium against the harmful effect of passive smoking in rabbits.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

Heart failure and angiotensin converting enzyme inhibition: problems and perspectives.

Heart failure has become the most widely studied syndrome in cardiology over the recent years. Despite the encouraging achievements by angiotensin converting enzyme (ACE) inhibitors, the mortality of patients with chronic heart failure remains high. There are several factors which can potentially be responsible for the fact that about 80% of patients with a failing heart defy protection by ACE inhibitors: different activation of tissue and systemic renin-angiotensin system (RAS) in a particular heart disease and the distinct ability of various ACE inhibitors to block cardiac ACE, alternative pathways for angiotensin II formation (chymase), genetic polymorphism of the RAS system and the complexity of neuroendocrine activation. Moreover, chronic heart failure can provoke disturbances in the reactivity of peripheral vessels and metabolism of striated muscles. These factors may then potentiate the vicious circle of heart failure. New therapeutic approaches, which could further reduce the mortality in patients with heart failure involve angiotensin II type 1 receptor antagonists, beta-blockers, aldosterone antagonists and blockers of the endothelin receptor. A number of questions associated with functions of the RAS still remain open and their solution could be of substantial benefit for patients with a failing heart.

Adrenergic beta-Antagonists↗
PubMed1999

Effect of captopril in L-NAME-induced hypertension on the rat myocardium, aorta, brain and kidney.

Long-term administration of NG-nitro-L-arginine methyl ester (L-NAME) induces development of hypertension and hypertrophy of the left ventricle in rats. The aim of the present study was to demonstrate the effect of chronic L-NAME treatment on DNA and RNA concentration, and protein synthesis in the rat heart, aorta, brain and kidney and to determine the effect of angiotensin converting enzyme (ACE) inhibitor captopril on these potential alterations. Four groups of rats were investigated: control, L-NAME (40 mg kg-1 day-1), captopril (100 mg kg-1 day-1), and L-NAME (40 mg kg-1 day-1) + captopril (100 mg kg-1 day-1). NO synthase activity in the heart, aorta, brain and kidney was found to be decreased in the L-NAME group. In the group of rats treated with L-NAME + captopril, captopril did not affect NO synthase inhibition. Captopril, however, completely prevented development of hypertension and left ventricular hypertrophy in this group. In the L-NAME group, DNA and RNA concentrations, as well as [14C]leucine incorporation, were significantly increased in all the tissues investigated. In the L-NAME + captopril group, captopril completely prevented the enhancement of DNA and RNA concentrations and [14C]leucine incorporation in all tissues compared to the L-NAME group. Moreover, a significant decrease in RNA concentration and [14C]leucine incorporation below control values was found in the captopril group as well as the L-NAME + captopril group in all the tissues investigated. We conclude that captopril prevented the development of hypertension and increase in nucleic acid concentration and protein synthesis in the heart, aorta, brain and kidney in rats treated with L-NAME + captopril. However, this protective effect of captopril was not associated with increased NO synthase activity in this model of hypertension.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

[Diagnosis of Duchenne and Becker muscular dystrophy in Slovak patients using multiplex polymerase chain reaction].

The authors of the paper describe the diagnostic method of deletion in the dystrophin gene by means of an improved variant of the polymerase chain reaction--so called multiplex PCR. The authors analyzed a group of 66 patients with developed clinical symptoms of the disease. The deletion screening included 22 exones of the dystrophine gene and it was performed in 5 multiplex PCR reactions. 20 patients yielded a verified deletion which was pre-assessed by Southern's hybridization. The relative simplicity of multiplex PCR which does not require the use of radioisotopes, its low time and financial needs, make this method to represents an appropriate alternative of Southern's hybridization in the assessment of deletion of the dystrophine gene. (Fig. 1, Ref. 19.)

Dystrophin↗
PubMed1998

Captopril attenuates proteosynthesis in the aorta and decreases endothelaemia in rabbits with aortic insufficiency.

The effect of the angiotensin converting enzyme (ACE) inhibitor, captopril, on proteosynthesis in the aorta, acetylcholine-stimulated aortic relaxation and endothelaemia (circulating endothelial cells) was investigated in rabbits with aortic insufficiency. The animals were studied 28 days after experimental intervention. Cardiac volume overload stimulated proteosynthesis in the aorta as reflected by increased ribonucleic acid (RNA) concentration and [14C] leucine incorporation into proteins of the aorta. Moreover, the number of endothelial cells in the blood was increased. The administration of captopril starting from the second day of the haemodynamic overload, partially prevented the increase both in aortic proteosynthesis and in endothelaemia. Despite these alterations, the relaxing ability of the aorta to acetylcholine was not changed either by the haemodynamic overload or by captopril. We conclude that the increase of proteosynthesis in the aorta and of endothelaemia in the early period of chronic cardiac volume overload in rabbits were partially prevented by chronic captopril treatment. Neither aortic insufficiency nor captopril changed the acetylcholine-induced relaxation of the aorta.

Acetylcholine↗
PubMed1997

Protein remodelling of the heart in NO-deficient hypertension: the effect of captopril.

Long-term administration of NG-nitro-L-arginine methyl ester (L-NAME) induces development of NO-deficient hypertension. The aim of the present study was to determine whether treatment with the angiotensin-converting enzyme (ACE) inhibitor captopril can prevent hypertension, left ventricular (LV) hypertrophy, changes in nucleic acid concentration, protein synthesis and protein profile of the left ventricle. Four groups of rats were investigated: control, L-NAME 40 mg/kg/day, captopril 100 mg/kg/day, L-NAME 40 mg/kg/day along with captopril 100 mg/kg/day. NO-synthase activity in the left ventricle was found to be decreased by 69% in the L-NAME group. Captopril did not influence this inhibition of NO-synthase activity. However, it completely prevented hypertension and left ventricular hypertrophy development. The increase in left ventricular RNA and DNA concentration and -14C-leucine incorporation observed in the L-NAME group was completely prevented by simultaneous captopril treatment. The protein profile of the left ventricle in the L-NAME group was characterized by higher concentration of metabolic proteins (MP), soluble collagenous proteins (SCP) and of hydroxyproline in insoluble collagenous proteins (ICP). The concentration of hydroxyproline in ICP was significantly decreased by simultaneous captopril treatment. We conclude that captopril prevented the development of hypertension, left ventricular hypertrophy, increase in nucleic acid concentration and diminished collagen concentration by mechanisms different from affecting NO-synthase activity.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Effect of captopril on the development of left ventricular hypertrophy in rabbits with aortic insufficiency.

We investigated the effect of captopril on the growth of the left ventricle in an experimental model of aortic insufficiency. Four groups of rabbits were studied 28 days after experimental intervention: 1. control, 2. control with captopril (10 mg/kg/day), 3. aortic insufficiency, 4. aortic insufficiency with captopril (10 mg/kg/day). Aortic insufficiency induced hypertrophic growth of the left ventricle demonstrated by increased weight and ribonucleic acid (RNA) concentration. Administration of captopril only slightly attenuated the weight increase of the left ventricle and the increase in concentration of left ventricular RNA. However, captopril reduced the concentration of left ventricular deoxyribonucleic acid (DNA) both in the control and even more in the group with aortic insufficiency. The chronic haemodynamic overload enhanced mitochondrial respiration in the left ventricle which was not influenced by captopril. We conclude that captopril in the dose 10 mg/kg/day did not prevent hypertrophy of the left ventricle but reduced left ventricular DNA concentration.

Angiotensin-Converting Enzyme Inhibitors↗