Biotransformation and toxicity effect of monoanthraquinone dyes during Bjerkandera adusta CCBAS 930 cultures.

The aim of this study was to evaluate of possibility of biotransformation and toxicity effect of monoanthraquinone dyes in cultures of Bjerkandera adusta CCBAS 930. Phenolic compounds, free radicals, phytotoxicity (Lepidium sativum L.), ecotoxicity (Vibrio fischeri) and cytotoxicity effect were evaluated to determine the toxicity of anthraquinone dyes before and after the treatment with B. adusta CCBAS 930. More than 80% of ABBB and AB129 was removed by biodegradation (decolorization) and biosorption, but biodegradation using oxidoreductases was the main dye removing mechanism. Secondary products toxic to plants and bacteria were formed in B. adusta strain CCBAS 930 cultures, despite efficient decolorization. ABBB and AB129 metabolites increased reactive oxygen species (ROS) production in human fibroblasts, but did not increase LDH release, did not affect the resazurine reduction assay and did not change caspase-9 or caspase-3 activity.

Better cognitive and physical performance is associated with higher blood pressure in centenarians.

OBJECTIVES: Knowledge of rational, evidence based health care in the hundred-year-old is still poor. The aim of the study was to evaluate health and functional state in hundred-year-old inhabitants of Upper Silesia, Poland, with a focus on the heart and vascular function. PARTICIPANTS: Medical and nursing assessment at places of residence was performed in thirty five 100.7±1.4 (mean±SD) year-old subjects, 28 women, and 7 men. MEASUREMENTS: The protocol included Mini-Mental State Examination (MMSE), Barthel Index (BI) and laboratory tests. A telephone follow-up was performed 180 days after the initial examination. RESULTS: Most subjects had increased systolic blood pressure (BP), diminished albumin and folate serum levels as well as decreased Glomerular Filtration Rate. According to the quadratic polynomial regression model MMSE and BI were dependent on BP. Higher BP was associated with better performance and survival. Those who survived more than 180 days had lower levels of CRP and VCAM-1 and higher level of sCD40L. CONCLUSION: The relationships between functional scales, survival and blood pressure suggest a beneficial effect of elevated BP on both mental and physical performance in centenarians. Further studies should determine an optimal balance between risk and benefits of elevated blood pressure in the oldest old people.

Activity of antioxidant enzymes in children from families at high risk of premature coronary heart disease.

A positive family history of coronary heart disease (CHD) is one of the most predictive risk factors of CHD. Many children with increased risk of CHD because of their positive family history of CHD do not present other risk factors, such as altered serum lipid profile. Oxidative stress plays an important part in the pathogenesis of atherosclerosis. Serum antioxidants and intracellular enzymatic antioxidants composed mainly of glutathione peroxidase (GSH-Px), catalase (CAT), superoxide dismutase (SOD) and glutathione reductase counterbalance oxidative stress. Diminished activity of this system may lead to accelerated progression of atherosclerosis. The aim of this study was to assess the activity of CAT, GSH-Px, SOD and glutathione reductase in children with a family history of premature CHD who did not present any other major risk factors of CHD (diabetes, obesity, dyslipidaemia or hypertension). Twenty-two healthy children from high-risk families, selected according to the National Cholesterol Education Program definition, were enrolled in the study. The control group comprised 18 children without a family history of CHD. All the children were healthy and had been screened for hyperlipidaemia, diabetes, hypertension and obesity prior to the study. The erythrocyte activity of CAT, GSH-Px, SOD and glutathione reductase was assessed. Children at high risk of CHD had a statistically significant lower level of GSH-Px and CAT activity than the children in the control group. There were no statistically significant differences in the activity of SOD and glutathione reductase.

Fibronectin gene polymorphism in patients with lung cancer.

Fibronectin (FN) is a glycoprotein component of connective tissue. It is involved in cancer progression. FN plays a role in non-neoplasmatic lung pathology in which fibronectin gene polymorphisms (RFLPs) have been studied. The aim of our work was to evaluate the frequency of two of fibronectin RFLPs: genotypes AB, AA, BB (HaeIII) and CD, CC, DD (MspI) in patients with lung cancer. The studied group consisted of 63 patients with squamous cell lung cancer and 53 controls without any malignant or proliferative disease. There were no statistically significant differences in the distribution of studied genotypes between lung cancer patients and controls.

Plasma levels of von willebrand factor, endothelin-1, prostacyclin and thromboxane in children from families with high risk of premature coronary artery disease.

The aim of the study was to assess the plasma levels of endothelial injury markers in children from families with high risk of premature coronary heart disease (CHD) without other common CHD risk factors (hyperlipidaemia, obesity, hypertension, low physical activity). The study comprised 48 children, including 24 children from high-risk families (HR), according to the NCEP (National Cholesterol Education Programme) criteria: one or two parents had clinical manifestation of cardiovascular disease before the age of 65 years (mother) or 55 years (father). The control group included 24 healthy children with no familial history of cardiovascular disease. All the children were normolipidaemic according to the NCEP and the European Atherosclerosis Society criteria for children aged 2-19 years. In the HR group, the concentration of vWf was significantly elevated in comparison to that in the control group (p<0.0001). Plasma concentrations of ET-1 and TxB2 did not differ significantly between the HR group and the controls. Plasma concentrations of the 6-ketoPGF1alpha in the HR group and in the respective age and gender HR subgroups were significantly lower compared with those of the control group (p<0.00005). Concentration of vWf in the HR group was negatively correlated with the concentration of 6-ketoPGF1alpha (r = -0.47; p<0.05) and positively correlated with TxB2 (r=0.39; p<0.01). In a logistic regression analysis, we found that the 6-ketoPGF1alpha concentration in the lower quartile (< 16.1 pmol/L) was associated with a 3.4-fold odds of inclusion in the high-risk group versus the upper quartile (>23.0 pmol/L).

Soluble ICAM-1, VCAM-1 and E-selectin in children from families with high risk of atherosclerosis.

The genetic predisposition for cardiovascular disease seems to play an important role in atherogenesis. Atherosclerosis, which can be clinically asymptomatic for many years, begins early in life. Therefore finding markers of early atherosclerotic process would be of great importance for screening and early treatment of these children. As the result of endothelial dysfunction, the adhesion molecules (VCAM-1, ICAM-1, ELAM) are overexpressed. These molecules are shed from the surface and can be measured, as soluble forms in serum. Therefore they can be regarded as early markers of atherosclerosis. The aim of the study was to measure the serum levels of soluble adhesion molecules ELAM, ICAM-1, VCAM-1 and plasma lipid profile--total (TC), LDL (LDL-C) and HDL-cholesterol (HDL-C) and triglycerides (TG) in children from families of high risk for cardiovascular diseases. Forty-eight children were studied, 24 children from high risk families, according to NCEP definition: one or two parents had clinical manifestation of cardiovascular disease before the age of 65 years (mother) or 55 years (father). Twenty-four healthy children without familial history of cardiovascular disease were used as the control. Children of either group did not have any metabolic diseases. The concentration of sELAM, sICAM-1 and sVCAM-1 were assessed using ELISA kits. Soluble ICAM-1 level was significantly higher in high risk group in comparison to control (p<0.02). The soluble VCAM-1 and ELAM levels did not differ significantly between the groups. There were no changes in total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides between the groups. In normolipidemic children from families with high risk for atherosclerosis the soluble ICAM-1 levels are significantly higher as compared to control.

The influence of angiotensin-converting enzyme inhibitors on the aorta elastin metabolism in diet-induced hypercholesterolaemia in rabbits.

Aortic elastin turnover is significantly accelerated in atherosclerosis, partly because of activation of the renin-angiotensin-aldosterone system caused by hypercholesterolaemia. We postulated that angiotensin-converting enzyme inhibitors (ACE-I) prevent the aortic elastin loss in experimental hypercholesterolaemia. Two doses of ACE-I (captopril, enalapril and quinapril) were used: a dose equivalent to that applied to human subjects and a dose 10 times higher. We found that the increase in serum and aortic elastolytic activity in cholesterol-fed rabbits was prevented by high-dose captopril. The elastin content in aorta homogenates from cholesterol-fed rabbits was significantly decreased. The higher dose of captopril, but no other ACE-I, prevented this decrease in aortic elastin content. In cholesterol-fed rabbits the elastin-bound calcium content was significantly elevated. The higher doses of captopril and enalapril lowered the elastin-bound calcium content. In serum and aortic homogenates of cholesterol-fed rabbits, ACE activity was elevated by 15% and 77%, respectively. Both doses of captopril, enalapril and quinapril prevented this cholesterol-induced increase in serum and aortic ACE activity. We conclude that: 1) administration of captopril at doses 10 times higher than those used in humans prevents hypercholesterolaemia increased aortic elastin loss. 2) higher doses of captopril and enalapril prevent the hypercholesterolaemia-induced increase in aortic elastin-bound calcium.

[HMG-CoA reductase inhibitors in prevention of cardiovascular diseases: new mechanisms, aspects and trials]. / Inhibitory reduktazy HMG-CoA w prewencji chorób ukladu krazenia--nowe mechanizmy, aspekty, programy.

Use of lipid-lowering drugs in both primary and secondary prevention of cardiovascular disease (CVD) decreases significantly risk of myocardial infarction, stroke, incidence of cardiovascular events, reduces the cardiovascular mortality and morbidity as well as total mortality. HMG-CoA reductase inhibitors (statins) are most potent cholesterol-lowering drugs. Statins act by inhibition of HMG-CoA reductase activity, a rate--limiting step in synthesis of cholesterol and important metabolites of mevalonate--isoprenoids. The mechanisms by which favourable antiatherogenic actions of statins occur are complex. Statins inhibit proliferation and migration of vascular smooth muscle cells, reduce free-radicals generation and LDL modification, lower Lp(a) concentration, inhibit macrophage-derived foam cells accumulation and inhibit activation of platelets, thromboxane and PAI-1 synthesis. Use of statins in the therapy of hypercholesterolemia is presently recommended by NCEP, especially in high-risk groups (diabetes, post-CABG and PTCA, kidney and heart transplantation). Nevertheless, patients with CAD and moderately elevated LDL-C levels also benefit from the treatment with statins. Because of high costs of the therapy, statins of most favourable pharmacoeconomic profile should be used.

The influence of angiotensin converting enzyme inhibitors on lipid peroxidation in sera and aorta of rabbits in diet-induced hypercholesterolemia.

In hypercholesterolemia increased lipid and lipoprotein peroxidation occurs. The renin-angiotensin system plays an important role in atherogenesis. Angiotensin II induces smooth muscle cells proliferation and stimulates oxidation of LDL particles and foam cell accumulation. Inhibition of ang II production leads to decrease in lipid peroxide production. The aim of this study was to assess the lipid peroxidation expressed as concentration of thiobarbituric acid reactive species (TBARS) in sera and aorta homogenates after administration of two doses of angiotensin-converting enzyme (ACE) inhibitors (captopril, enalapril and quinapril) in diet-induced hypercholesterolemia in rabbits. Sixty-four New Zealand rabbits were used. Animals were fed with standard fodder, special diet (1% cholesterol content) or special diet + tested ACEI. Two doses of ACE inhibitors were used: i), equivalent to applied to humans, ii), dose 10 times higher. The animals were divided into 8 groups: control, standard fodder; B, special diet; C1, C2, special diet + captopril in doses 2.5 and 25 mg/kg/24 h, respectively; E1, E2, special diet + enalapril in doses 0.75 and 7.5 mg/kg/24 h, respectively; Q1 and Q2, special diet + quinapril in doses 0.75 and 7.5 mg/kg per day, respectively. In cholesterol-fed rabbits and in groups receiving lower doses of tested ACE inhibitors, the serum TBARS concentration at 6 months was significantly higher in comparison to the control. The higher doses of enalapril, quinapril and captopril, prevented the cholesterol-induced rise in TBARS concentration. Lower dose of captopril attenuated the rise in TBARS concentration, it was significantly lower in comparison to group B, but higher than in the control group. In animals from groups B, E1, C1, Q1 TBARS concentration in aortae was significantly higher as compared to control group. Both doses of captopril and higher doses of enalapril and quinapril inhibited the rise of lipid peroxides concentration induced by cholesterol-rich diet.

Serum HDL cholesterol concentration in patients with squamous cell and small cell lung cancer.

Cancer patients often present altered serum lipid profile including changes of HDL cholesterol level. The aim of our work was to evaluate serum level of HDL cholesterol in patients with squamous cell and small cell lung cancer and its dependence on histological type and clinical stage of lung cancer. Fasting serum level of HDL cholesterol was analysed in 135 patients with newly diagnosed lung cancer and compared to a control group of healthy men. All lung cancer patients, as well as subgroups of squamous cell and small cell lung cancer had statistically significantly lower HDL cholesterol concentration than controls. There were no statistically significant differences of HDL cholesterol level between the histological types or between clinical stages of each histological type of lung cancer.

[Genetic predisposition to cardiovascular diseases]. / Predyspozycja genetyczna do chorób ukladu sercowo-naczyniowego.

The development of cardiovascular system disorders depends on both environmental and genetic factors. Precise mechanism by which genetic factors may promote atherosclerotic lesion formation is still under investigation. From multiple candidate genes for cardiovascular disorders the special attention should be paid to that which control synthesis of molecules involved in atherosclerosis process. For now lots of experiments have been done to test specific genes speculated to be crucial for the onset and progression of atherosclerosis, including genes of lipoprotein metabolism, coagulation and fibrinolysis system, renin-angiotensin system and substances influencing the metabolism of arterial wall. Many of them showed the association between tested polymorphisms and pathogenesis of cardiovascular diseases.

Serum total cholesterol and triglycerides levels in patients with lung cancer.

Epidemiological studies indicate that low serum total cholesterol level may increase the risk of death due to cancer, mainly lung cancer. The aim of our study was to evaluate serum levels of total cholesterol (TC) and triglycerides (TG) in patients with squamous cell and small cell lung cancer and their dependence on the histological type and the clinical stage of the neoplasm. Lung cancer patients (n=135) and healthy controls (n=39) entered the study. All lung cancer patients had higher rate of hypocholesterolemia and lower TC and TG levels than the control group. TC concentration was lower in lung cancer patients and in both histological types in comparison with the control group, TG level was lower only in patients with squamous cell lung cancer. There were no statistically significant differences of TC and TG levels between the histological types, or between the clinical stages of each histological type.

Serum LDL cholesterol concentration and lipoprotein electrophoresis pattern in patients with small cell lung cancer.

Epidemiological studies show that people with low level of total cholesterol have a greater risk of death due to cancer, predominantly lung cancer. The aim of our study was to evaluate serum level of LDL cholesterol and lipoprotein electrophoresis pattern in patients with small cell lung cancer and their dependence on clinical stage of the neoplasm. The studied group consisted of 34 patients with newly diagnosed small cell lung cancer and 39 healthy controls. Fasting level of LDL cholesterol was analyzed and lipoprotein electrophoresis was performed. There were no statistically significant differences of evaluated serum lipid parameters between lung cancer patients and controls, and between the clinical stages of small cell lung cancer.

[The influence of angiotensin-converting enzyme inhibitors on collagen content of the aorta wall in experimental hypercholesterolemia]. / Wplyw inhibitorów enzymu konwertujacego na zawartosc kolagenów w scianie aorty w doswiadczalnej hipercholesterolemii.

In atherosclerosis numerous qualitative and quantitative changes in connective tissue metabolism parameters in serum and aorta occur. In atherosclerosis there is an enhanced activity of local renin-angiotensin systems. It leads to overexpression of ANG II, both in serum and arterial wall. ANG II stimulates SMC to over-synthesize the collagens type I and III. Hyper-cholesterolemia is a form of metabolic injury which can both induce phenotypic change of SMC and activate RA system in arterial wall. ACEI lower the accumulation of collagens type I and III, and enhance elastin content in arterial wall in experimental hypertension. The aim of this study was to assess the influence of captopril, enalapril and quinapril on connective tissue metabolism of the aorta in experimental hyper-cholesterolemia. 64 male New Zealand rabbits were used. Animals were fed with standard fodder, special diet (1% cholesterol content) or special diet + tested ACEI. Two doses of ACE inhibitors were used: 1st--equivalent to doses applied to human subjects (in mg/kg of body weight), 2nd--dose 10 times higher. The animals were divided into 8 equal groups: K--standard fodder, B--special diet, C1, C2--special diet + captopril in doses 2.5 and 25 mg/kg/24 hours, respectively, E1, E2--special diet + enalapril in doses 0.75 and 7.5 mg/kg/24 hours, respectively, Q1 i Q2--special diet + quinapril in doses 0.75 and 7.5 mg/kg per day, respectively. The experiment lasted for 6 months. After 24 weeks the animals were sacrificed and aortae were excised for collagens assay. The statistical analysis was performed using ANOVA, followed by LSD test; p < 0.05 was considered statistically significant. The aorta collagens content of cholesterol-fed rabbits significantly increased. The tested ACEI (captopril, enalapril in both doses and quinapril in lower dose) had a preventive effect against the increase of aorta collagen content.

[Anti-atherosclerotic actions of HMG-CoA reductase inhibitors]. / Przeciwmiazdzycowe dzialanie inhibitorów reduktazy HMG-CoA.

Statins are most potent lipid-lowering drugs. The mechanisms of their action is specific inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) activity. HMG-CoA reductase catalyses the reduction of HMG-CoA o mevalonate and is rate-limiting step in cholesterol biosynthesis pathway. Mevalonate is considered to be not only an important intermediate of cholesterol synthesis, but also the source of isoprenoids which play important role in DNA replication and cell growth. It was shown that statins inhibit the proliferation and migration of vascular smooth muscle cell--key events in atherogenesis. HMG-CoA reductase inhibitors lower the reactivity of arterial wall to vasoconstrictor agents, decrease the concentration of lipoprotein [a]--an independent risk factor of atherosclerosis, inhibit the generation of free radicals and lipid peroxidation, decrease the number of macrophages in atherosclerotic lesion and finally, equilibrate the clotting-fibrynolysis processes of attennuating platelets function, reducing the tissue factor synthesis and decreasing the concentration of plasminogen activator inhibitors. Statins are presently considered by NCEP to be the drugs of first choice for treatment of hypercholesterolemia.

[Treatment of hypertension in postmenopausal women]. / Leczenie nadcisnienia u kobiet po menopauzie.

Epidemiological and clinical studies have defined the lower incidence of atherosclerotic vascular disease in women than in age-matched men. After menopause the difference becomes less significant, what is due to estrogen deficiency. The mechanism of vascular protective effect of estrogen involves inhibition of smooth muscle cell proliferation, protection of endothelium function and improvement of lipid metabolism. One of the most important risk factor of atherosclerosis is hypertension. The prevalence of hypertension in elderly women is extremely high-up to 80%. Because of absence of the hormonal replacement therapy effect on blood pressure, there is an indication for antihypertensive therapy in postmenopausal women. Angiotensin-converting enzyme inhibitors are the class of drugs which can lower cardiovascular mortality due to hypertension and atherosclerosis in elderly women. They improve impaired insulin sensitivity and inhibit activation of renin-angiotensin system, both processes leading to the development of hypertension in postmenopausal women. Angiotensin-converting enzyme inhibitors also possess a direct anti-atherosclerotic properties, like inhibition of smooth muscle cell proliferation and migration, protection of endothelium function, reduced macrophages activation and foam cell accumulation, protection of LDL particles and improvement of fibrinolysis.

[The role of DNA polymorphism in the renin-angiotensin system and the pathogenesis of cardiovascular diseases]. / Rola polimorfizmu DNA ukladu renina-angiotensyna w patogenezie chorób ukladu krazenia.

Myocardial infarction and stroke are the major cause of death in developed countries and are the clinical manifestation of atherosclerosis and hypertension. Both the environmental factors and genetic predisposition have an influence on the pathogenesis of these diseases. Despite we know lots of environmental risk factors and we made important advances in the prevention and treatment of mentioned diseases, our knowledge about the pathogenic linkage between genetic predisposition and cardiovascular diseases is still very little. Activation of the renin-angiotensin system has been proposed as a very important step in the pathogenesis of hypertension and atherosclerosis. In spite of vasoconstrictor activity, angiotensin II can stimulate migration and proliferation of vascular smooth muscle cells, macrophage-foam cells formation, adhesion and aggregation of platelets and fibrinolytic system inhibition. Angiotensin convertin enzyme inhibitors reduce the development of the atherosclerotic process after vascular injury and in hyperlipidemic animals. Blockade of renin-angiotensin system seems to be also effective in secondary prevention of myocardial infarction in men. In sum, the genetic variations inside the renin-angiotensin system which may affect the function of its components might have an influence on genetic predisposition to cardiovascular diseases. The paper deals with the current state of knowledge on association between polymorphic variations in renin gene, angiotensinogen gene, angiotensin converting enzyme gene and AT1 receptor gene and primary hypertension, ischaemic heart disease and myocardial infarction.

[Lipids and atherosclerosis]. / Lipidy a miazdzyca tetnic.

Atherosclerosis is a degenerative pathology of blood vessels leading to coronary heart disease, myocardial infarction and stroke. The basic lesion of atherosclerosis is the fibrous plaque, which consists of lipids, smooth muscle cells, macrophages and connective tissue matrix. Data derived from experimental and clinical studies indicate the crucial role of elevated serum LDL-cholesterol concentration in the formation of atherosclerotic lesions. HDL removes cholesterol from the arterial wall, stimulates arterial prostacyclin synthesis, inhibits adhesion molecules expression, has antioxidant properties and protects against atherosclerosis. Lipoprotein (a) competes with plasminogen for its binding site, leading to reduced fibrinolysis and is an important link between thrombogenesis and atherosclerosis. The pathogenic role of lipids in atherogenesis is discussed.

[Anti-atherosclerotic action of hypotensive drugs]. / Przeciwmiazdzycowe dzialanie leków hipotensyjnych.

Hypertension is an important risk factor for the development of atherosclerosis. Traditional antihypertensive therapy is not fully effective in prevention of cardiovascular abnormalities of hypertension. Two classes of hypotensive drugs, calcium antagonists and angiotensin-converting enzyme (ACE) inhibitors, reduce atherosclerosis in several experimental models in animals. Anti-atherosclerotic effects of calcium antagonists include attenuation of endothelial dysfunction, prevention of LDL modification, stimulation of LDL receptor activity, inhibition of superoxide radical generation and inhibition of vascular smooth muscle cells proliferation and migration. In large angiographic trials calcium antagonists reduced the development of new atherosclerotic plaques. ACE inhibitors also lead to the lower incidence of atherosclerosis in experimental animals. They inhibit migration and proliferation of vascular smooth muscle cells, reduce macrophage-derived foam cell accumulation, preserve protective endothelium function, reduce LDL modification and increase fibrinolytic activity. It depends on reduced angiotensin II synthesis, increased concentration of kinins, substance P and angiotensin-(1-7), inhibition of leukotriene B4 formation and improvement of insulin action. In some studies they also reduce plasma lipids concentration, including lipoprotein (a). ACE inhibitors were found to be ineffective in prevention of restenosis after PTCA in human but data derived from large, multicenter trials indicate that they are effective in the secondary prevention of myocardial infarction.