Aronia melanocarpa extract reduces blood pressure, serum endothelin, lipid, and oxidative stress marker levels in patients with metabolic syndrome.

BACKGROUND: Experimental studies have shown that anthocyanins may exert pleiotropic effects. The aim of the study was to determine the influence of Aronia melanocarpa extract on blood pressure and serum concentration of endothelin-1 (ET-1), lipids, glucose, uric acid, C-reactive protein (CRP), fibrinogen, the antioxidant enzymes catalase (CAT), superoxide dysmutase (SOD), and glutathione peroxidase (GSH-Px), and lipid peroxidation (thiobarbituric acid-reacting substrates, TBARS) in erythrocytes of patients with metabolic syndrome (MS). MATERIAL/METHODS: The study comprised 22 healthy volunteers and 25 patients with MS. Patients with MS were treated with aronia extract (3 x 100 mg/day) for two months. The above parameters were measured. RESULTS: After two months of therapy, statistically significant decreases were observed in SBP (143.40+/-7.87 vs. 131.83+/-12.24 mmHg, p<0.001), DBP (87.20+/-9.9 vs. 82.13+/-10.33 mmHg, p<0.05), ET-1 (2.44+/-0.51 vs. 1.74+/-0.42 pg/ml, p<0.001), TC (242.80+/-34.48 vs. 227.96+/-33.07 mg/dl, p<0.001), LDL-C (158.71+/-35.78 vs. 146.21+/-34.63 mg/dl, p<0.01), TG (215.92+/-63.61 vs. 187.58+/-90 mg/dl, p<0.05), TBARS (0.0712+/-0.0191 vs. 0.0362+/-0.0135 micromol/g-Hb, p<0.001), and CAT (261.30+/-59.78 vs. 213.34+/-47.36 U/mg-Hb) and significant increases in SOD (2380.63+/-419.91 vs. 3066.53+/-542.24 U/g-Hb, p<0.001), GSH-Px (12.60+/-5.97 vs. 19.18+/-9.09 U/g-Hb, p<0.01), and fibrinogen levels (249.20+/-27.17 vs. 276.67+/-57.41 mg/dl, p<0.05) compared with the baseline values. CONCLUSIONS: Aronia extract may be of benefit to patients with MS. This seems to result from the influence of anthocyanins and possibly other flavonoids on blood pressure, serum level of ET-1, lipids, and oxidative status (GSH-Px, SOD, TBARS).

[Effect of anthocyanins from Aronia melanocarpa on blood pressure, concentration of endothelin-1 and lipids in patients with metabolic syndrome]. / Wplyw antocyjanin z aronii czarnoowocowej na cisnienie tetnicze oraz stezenie endoteliny-1 i lipidów u pacjentów z zespolem metabolicznym.

THE AIM OF THE STUDY: To estimate the influence of anthocyanins from Aronia melanocarpa on blood pressure, concentration of endothelin-1 (ET-1), serum lipids, fasting glucose, uric acid and membrane cholesterol in erythrocytes of patients (pts) with metabolic syndrome (MS). MATERIAL AND METHODS: The study comprised 22 healthy volunteers and 25 pts with MS treated with anthocyanins (3 x 100 mg/d) for 2 months. Waist circumference (> or = 80 cm for women and > or =94 cm for men), triglicerydes (TG) level >150 mg/dl (1.7 mmol/l), cholesterol-HDL (HDL-C) level < 40 mg/dl (1.0 mmol/l) for men and <50 mg/dl (1.3 mmol/l) for women, systolic blood pressure (SBP) >130 mmHg and/or diastolic blood pressure (DBP) >85 mmHg were inclusion criteria for patients with MS. Before and after 2 months of treatment the following parameters were determined: SBP, DBP, serum lipids (total cholesterol--TC, cholesterol LDL--LDL-C, cholesterol HDL--HDL-C, TG--by enzymatic method), membrane cholesterol in erythrocytes (method of IIcy), ET-1 (immunoenzymatic method), fasting glucose level was (colorimetric method), uric acid (enzymatic--colorimetric method). RESULTS: After two months therapy of anthocyanins from Aronia melanocarpa in comparison with baseline it was observed a significant decrease of: SBP (144.20 +/- 9.97 vs. 131.83 +/- 12.24 mmHg, p < 0.001) and DBP (87.20 +/- 9.9 vs. 82.13 +/- 10.33 mmHg, p < 0.05), TC (242.80 +/- 34.48 vs. 227.96 +/- 33.07 mg/dl, p < 0.001), LDL-C (158.71 +/- 35.78 vs. 146.21 +/- 34.63 mg/dl, p < 0.01), TG (215.92 +/- 63.61 vs. 187.58 +/- 90 mg/dl, p < 0.05), ET-1 (2.44 +/- 0.51 vs. 1.74 +/- 0.42 pg/ml, p < 0.001) and membrane cholesterol (4.85 +/- 0.65 vs. 2.81 +/- 0.54 mmol/Lpc, p < 0.001), uric acid and fasting blood glucose levels did not change significantly after study cessation. CONCLUSIONS: The results of our study show that anthocyanins from Aronia melanocarpa may be of benefit to patients with MS as for as atherosclerosis prevention is concerned. It seems to result from anthocyanins influence on blood pressure, serum lipid and endothelin-1 level.

[Melatonin in the treatment of atherosclerosis]. / Melatonina w leczeniu miazdiycy.

Atherosclerosis is currently concerned as a chronic inflammatory process, which is response to an endothelial damage. Therapy of atherosclerosis should influence on various mechanisms. Substances which can prevent and treat this disorder are still being investigated. Melatonin exerts anti-inflammatory and antioxidative properties, which implies that it can be useful in the treatment of atherosclerosis. Melatonin neutralizes ROS (reactive oxygen species), increases antioxidative enzymes activities and glutathione levels, prevents electron leakage from mitochondrial respiratory chain, acts synergistically with vitamins C, E, and glutathione. Melatonin reduces levels of proinflammatory cytokines: IL-6, IL-12, TNF-alpha, IFN-gamma. In vivo studies and experiments on animals melatonin exerts beneficial effect on serum lipids, prevents LDL oxidation, decreases TBARS levels, increases total antioxidant capacity. However, some studies suggest that melatonin can exert atherogenic effects in animals. Clinical studies on patients who are in risk of atherosclerosis development are required.

[The erythrocyte membrane structure in patients with mixed hyperlipidemia]. / Struktura blon erytrocytów u pacjentów z mieszana hiperlipidemia.

In hypercholesterolemia the damage to the plasma membranes of erythrocytes is observed. This may result from higher concentration of cholesterol in plasma and membranes, lipids peroxidation and changes in protein conformation. The aim of the study was to estimate the membrane fluidity, concentration of cholesterol (Ch), phospholipids (PL), ratio of Ch/PL, thiobarbituric acid reaction substances (TBARS) in the isolated erythrocyte membrane of patients with mixed hyperlipidemia. The study comprised 50 patients in the age from 45 to 65 with the initial concentrations of total cholesterol (TC) > 200 mg/dl (5.2 mmol/l); cholesterol LDL (LDL-C) > 160 mg/dL (4.1 mmol/l); triglicerides (TG) > 150 mg/dL (4.5 mmol/L) and 22 healthy controls. The plasma lipids concentrations were determined by enzymatic method, the concentration of cholesterol membrane (by method of Ilcy), phospholipids (by method of Bartlett), lipids peroxidation (by method of Stocks and Dormandy) and the erythrocyte membrane fluidity (by a spin-label paramagnetic resonance method using 5-doxylstearic acid - 5-DSA, and 16-doxylstearic acid - 16-DSA). The order parameter S was determined using 5-DSA; 16-DSA was used to estimate the correlation taub and tauc. In group of patients with mixed hyperlipidemia in comparison to the control group it was noticed a significant increase of the mean values of order parameter S (0.74 +/- 0.01 vs. 0.72 +/- 0.005, p < 0.001), of membrane cholesterol concentration (3.39 +/-0.98 vs. 1.93 +/- 0.93 mmol/l pc, p < 0.001), ratio Ch/PL (2.32 +/- 1.22 vs. 1.22 +/- 0.44; p < 0,001) and TBARS (2.91 +/- 0.74 vs. 1.5 +/- 0.4 nmol/mg protein). The differences of the correlation times and phospholipids concentrations between the groups were not statistically significant. Significant correlation between the order parameter S and concentrations of TC, LDL-C in plasma and membrane cholesterol was observed. On the base of given results we conclude that mixed hyperlipidemia may have influence on the erythrocyte membrane structure caused significant decrease of membrane fluidity in the superficial layer without any significant changes in deeper layer and significant increase of membrane cholesterol and TBARS.

[Effect of fluvastatin extended release on the protein-lipid structure of erythrocyte membrane and C-reactive protein in patients with hyperlipidemia]. / Wplyw fluwastatyny o powolnym uwalnianiu na strukture bialkowo-lipidowa blon erytrocytów i bialko C-reaktywne u pacjentów z hiperlipidemia.

UNLABELLED: The aim of the study was to estimate the effects of 4-weeks therapy of fluvastatin extended release (XL) on lipids serum, C-reactive protein (CRP), erythrocyte structure membrane (thiobarbituric acid reactive substances--TBARS concentrations, membrane cholesterol and the activity of Na+K(+)-ATPase in erythrocytes) in patients with hyperlipidemia without any clinical signs of atherosclerosis. MATERIAL AND METHODS: The study comprised 37 persons, including 15 healthy volunteers and 22 patients with hyperlipidemia (TC > 200 mg/dl, LDL-C > 130 mg/dl, TG < 400 mg/dl) treated with fluvastatin XL 80 mg/d. Before and after 4 weeks of active treatment the following parameters were determined: lipids (by enzymatic method using BioMerieux tests), CRP (by immunoturbidimetric method), TBARS concentrations (by method of Stock and Dormandy), membrane cholesterol (method of Ilcy), Na+K(+)-ATPase activity (method of Bartosz et al.). RESULTS: It was noticed significantly higher concentrations of CRP, TBARS, membrane cholesterol and lower activity of Na+K(+)-ATPase in erythrocytes of patients with hyperlipidemia than in the control group. Fluvastatin XL caused a significant decrease in serum TC (by 18%), LDL-C (by 24%), TG (by 16%), CRP (by 23%) and TBARS (by 31%), membrane cholesterol (by 30%) in comparison to the initial values before active therapy. The activity of Na+K(+)-ATPase didn't significantly change. The mean values of CRP, TBARS, membrane cholesterol level after active treatment are still higher than in the control group. CONCLUSION: The short-term treatment of fluvastatin extended release wasn't enough efficient to compensate disorders in erythrocyte membrane structure of patients with hyperlipidemia.

[The comparison in vitro the effects of pravastatin and quercetin on the selected structural parameters of membrane erythrocytes from patients with hypercholesterolemia]. / Porównanie in vitro wplywu prawastatyny i kwercetyny na wybrane parametry strukturalne blon krwinek czerwonych u pacjentów z hipercholesterolemia typu II.

UNLABELLED: The aim of the study was to compare the effects in vitro of pravastatin and quercetin on the structural parameters of erythrocyte membrane of patients with hypercholesterolemia type II. MATERIAL AND METHOD: 2% suspensions of erythrocytes from hypercholesterolemic patients (n = 30, mean age 54.2 +/- 6.9) and healthy donors (n = 22, mean age 53.1 +/- 6.1) were incubated for 24 hours at 37 degrees C with or without pravastatin (9 microM, 90 microM), quercetin (10 microM, 50 microM, 100 microM). After the incubation we assessed, the cholesterol content (by method of Ilcy), the level of TBARS (by method of Stocks and Dormandy), the membrane fluidity (by paramagnetic resonance). RESULTS: In erythrocytes of patients (pts) with hypercholesterolemia type II (hip II) in comparison to the control group significantly higher mean values of membrane cholesterol content (0.065 +/- 0.013 vs 0.039 +/- 0.008AU, p < 0.001), the order parameter S (0.775 +/- 0.018 vs 0.752 +/- 0.018, p < 0.001) and TBARS level (2.91 +/- 1.01 vs 1.60 +/- 0.41 mmol/gHb, p < 0.001) were observed. After incubation of erythrocytes from hypercholesterolemic patients with pravastatin it was noticed the significant decrease (in dependence on statin concentration - 9 microM, 90 microM) of mean cholesterol content (by 23% and 37%, respectively) and the order parameter S (by 2% and 3%) in comparison the values after erythrocyte incubation without statin. Pravastatin didn't influence on the level of TBARS. After incubation with quercetin it was observed the significant decrease of membrane cholesterol (26-33%), the order parameter S (maximum by 4%) i TBARS levels (16-25%). CONCLUSIONS: 1. Pravastatin and quercetin, in vitro, in similar degree decrease the level of membrane cholesterol and advantageously influence on membrane fluidity of erythrocytes from patients with hypercholesterolemia type II. 2. Pravastatin, in vitro, in opposite to quercetin doesn't influence on lipid peroxidation in erythrocytes of patients with hypercholesterolemia type II and healthy.

[Estimation of the correlation between hemostatic parameters and serum lipids in patients with hyperlipidemia type II after simvastatin therapy]. / Ocena korelacji miedzy parametrami hemostazy a lipidogramem surowicy u chorych na hiperlipidemie typu II po leczeniu simwastatyna.

UNLABELLED: The aim of the study was to evaluate the correlation between hemostatic parameters such as: the activity of antithrombin III and factor X, thrombin generation, clot bound thrombin, fibrinogen and serum lipids in patients (pts) with hyperlipidemia (hlp) type II after 2-months treatment with simvastatin in dose 20 mg/day. MATERIAL AND METHODS: The study involved 22 pts with hip with the initial concentrations of total cholesterol (TC) > 230 mg/dL, LDL-cholesterol (LDL-C) > 130 mg/dL, triglicerides (TG) < 400 mg/dL, 22 healthy volunteers as the control group. The hemostatic parameters and serum lipids were estimated before and after active therapy. TC, HDL-C, TG were determined by enzymatic method, LDL-C was calculated by Friedewald'a formula. Thrombin generation and clot bound thrombin levels were estimated by spectrophotometric method with usage of chromogenic substrate S-2238, the activity of factor X and antithrombin III--by amidolytic methods. For correlation we used coefficient of linear correlation. RESULTS: After 2-months therapy with simvastatin in patients with hlp II it was observed significantly decrease of activity of factor X (20.94 +/- 19.04 vs. 9.44 +/- 7.31 mU/mL), thrombin generation (79.62 +/- 36.68 vs. 67.99 +/- 37.69 U/mL), clot bound thrombin (49.73 +/- 21.17 vs. 37.08 +/- 26.10 U/mL) and increase of antithrombin III activity (13.03 +/- 6.11 vs. 20.64 +/- 4.18 U/mL). The mean concentrations of fibrinogen didn't change during statin treatment (336.00 +/- 71.4 vs. 357.26 +/- 98.86 mg/dL). After simvastatin treatment it wasn't observed any significant correlation between the changes of hemostatic parameters and serum lipids. CONCLUSIONS: The short therapy of simvastatin therapy beneficial modifies hemostatic parameters. Lack of linear correlation between lipids changes concentrations and hemostatic parameters during simvastatin treatment suggests hypolipemic independent influence of statin on the coagulation system.

[Influence of combined, hypolipemic therapy on lipids and non-lipid atherosclerosis risk factors]. / Wplyw skojarzonej terapii hipolipemicznej na lipidy osocza i pozalipidowe czynniki ryzyka miazdzycy.

It is very difficult to reach therapeutic goals of lipids concentrations n patients with very high and high risk development of coronary heart disease during statin monotherapy. Treatment with high doses of statins is associated with significantly increase of serious adverse events, especially rhabdomiolysis. Therefore are taken much more often trials of the combined hypolipemic therapy. In this article, we briefly review the clinical trial data on the efficacy, safety and influence on non-lipid atherosclerosis factors of combined therapy statin with fibrates, statin with nicotinic acid and statin with ezetimibe.

Physicochemical modifications induced by statins therapy on human erythrocytes membranes.

UNLABELLED: In hyperlipidemia damage to the plasma membranes of erythrocytes is observed. It is supposed that statins by their beneficial impact on the serum lipids and pleiotropic effects may modify the membrane cell structure. MATERIAL AND METHODS: The aim of the study was to evaluate the effects of statins on erythrocyte membrane structure in patients (pts) with hyperlipidemia. The study involved 54 pts with the initial total cholesterol (TC) concentration > 200 mg/dl (6.5 mmol/l), low-density lipoprotein cholesterol (LDL-C) > 160 mg/dl (4.1 mmol/l) and triglycerides (TG) < 400 mg/dl (4.5 mmol/l) and 22 healthy individuals as the control group. After 8 weeks of hypolipemic diet, pts were randomized to two groups: A--27 pts treated with atorvastatin in a dose of 10 mg/day; S--27 pts treated with simvastatin in a dose of 40 mg/day. After 8 weeks of active therapy in all pts were determined: the activity of Na+K+-ATPase, erythrocyte membrane fluidity (the order parameter S), lipids peroxidation (thiobarbituric acid-reactive substances - TBARS), content of membrane cholesterol, concentration of SH groups and W/S ratio (which specifies the relations between the two kinds of the SH groups: the weakly--W bound, and the strongly--S bound). RESULTS: In the group of hyperlipidemic patients as compared to the control group we observed significantly higher values of the order parameter S, membrane cholesterol, TBARS, ratio W/S and significantly lower the activity of Na+K+-ATPase, SH groups concentration in membrane erythrocytes. Atorvastatin and simvastatin in a similar degree significantly increased the activity of Na'K'-ATPase (15.7% vs. 20.9%), the SH concentration groups (23.4% vs. 21.2%) and decreased TBARS (-41.8% vs. -41%), W/S ratio (-11.3% vs. S-12.1%). Simvastatin decreased stronger the membrane cholesterol (-30.0% vs. -24.5%; p < 0.05) and the values of parameter S (-5.1% vs. -3.5%, p < 0.05) than atorvastatin. CONCLUSIONS: A short-term therapy with statins exhibits a high hypolipemic efficacy and advantageous effects on the protein-lipid structure of erythrocyte membranes. Simvastatin at 40 mg/day dose increases the fluidity of erythrocyte membrane and decreases the membrane cholesterol level to a greater extent than does atorvastatin at 10 mg/day dose.

[Statins in chronic heart failure--new indication?]. / Statyny w przewleklej niewydolnosci serca --nowe wskazanie?

Chronic heart failure (CHF) is connected with very high risk of death. Discovery of neurohormonal mechanisms which contribute to pathogenesis of CHF changed therapeutic management of CHF. It was indicated that statins may exert beneficial effects in patients with CHF through preventing acute coronary syndromes, reducing myocardial hypertrophy, decreasing activation of renin-angiotensin-aldosterone system and sympathetic system, inhibitory effects on inflammatory cytokines and metalloproteinases, improving endothelial function. Usefulness of statins in CHF is however controversial. There is some evidence that lower serum cholesterol concentrations relate to impaired survival in patients with CHF. Before data from large scale trials (CORONA, GISSI-HF, UNIVERSE) will be published, statin therapy in CHF must be recommended carefully.

[The anti-inflammatory and antioxidants effects of micronized fenofibrate in patients with visceral obesity and dyslipidemia]. / Dzialanie przeciwzapalne i antyoksydacyjne zmikronizowanego fenofibratu u chorych z otyloscia brzuszna i dyslipidemia.

UNLABELLED: In recent studies it was observed the pleiotropic properties beyond hypolipemic effects of fenofibrate: anti-inflammatory, antioxidants effects, positive impact on glucose metabolism, thrombosis, fibrinolytic system endothelial dysfunction. THE AIM OF THE STUDY: To estimate the effects of 4-weeks therapy of micronized fenofibrate in dose 267 mg/d on C-reactive protein (CRP), fibrinogen, thiobarbituric acid reaction substances (TBARS) concentrations in isolated erythrocyte membranes and the activities of antioxidants enzymes such: catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) in erythrocytes in patients with visceral obesity and atherogenic dyslipidemia. MATERIAL AND METHODS: The study comprised 55 patients (pts), including 20 healthy volunteers and 35 pts with visceral obesity and dyslipidemia (TG>180 mg/dl, HDL-C < 40 mg/dl for men, <50 mg/dl for women) treated with micronized fenofibrate (267 mg/d). Before and after 4 weeks of active treatment the following parameters were determined: lipids (by enzymatic method using BioMerieux tests), CRP (by immunoturbidimetric method), fibrinogen (by Clauss'a method), TBARS concentrations (by method of Stock and Dormandy), CAT (method of Bartosz et al.), GSH-Px (method of Rice-Evansa), SOD (method of Misra) activities. RESULTS: It was noticed significantly higher concentrations of CRP fibrinogen, TBARS and lower activities of CAT GSH-Px, SOD in patients with visceral obesity and atherogenic dyslipidemia than in the control group. The micronized fenofibrate caused a significant decrease in serum total cholesterol (by 15%), TG (by 38%), CRP (by 35%), fibrinogen (by 26%) and TBARS (by 33%) concentrations associated with a increase in CAT (by 35%), GSH-Px (by 63%), SOD (by 31%) activities. CONCLUSION: We conclude that micronized fenofibrate beyond hipolipemic efficacy demonstrates the antioxidative and anti-inflammatory properties in patients with visceral obesity and atherogenic dyslipidemia.

[The effect of statins on lipids peroxidation and activities of antioxidants enzymes in patients with dyslipidemia]. / Wplyw statyn na peroksydacje lipidów i aktywnosc enzymów antyoksydacyjnych w erytrocytach u pacjentów z dyslipidemia.

UNLABELLED: In recent studies it was observed antioxidant effects of statin independently on their hypolipemic effects. It is supposed that differences in statins pharmacological properties may cause different antioxidant actions. The aim of the study was to evaluate the effect of simvastatin, atorvastatin and pravastatin on plasma lipids, thio-barbituric acid reactive substances (TBARS) concentrations in the isolated erythrocytes membranes, activities of antioxidants enzymes in erythrocytes: catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) in patients (pts) with dyslipidemia. MATERIAL: The study comprised 114 pts, including 94 pts with dyslipidemia without concomitant chronic diseases and 20 healthy volunteers. Pts were qualified to treatment with statins if their LDL-cholesterol concentration (LDL-C) was above 160 mg/dL (4.1 mmol/l), total cholesterol (TC) > 250 mg/dl (6.5 mmol/l) and triglicerydes (TG) < 400 mg/dl (4.5 mmol/L). Pts were randomized to three groups: group I-n = 31 pts treated with atorvastatin (10 mg/d); group II-n = 31-simvastatin (20 mg/d), group III-n = 32 pravastatin (20 mg/d). METHODS: After 4 and 12 weeks of active treatment the following parameters were determined: TC, HDL-C, TG (by enzymatic method using bioMerieux tests); LDL-C was calculated from the Friedewald formula, TBARS concentrations (by method of Stock and Dormandy), CAT (method of Bartosz et al.), GSH-Px (method of Rice-Evansa et al.), SOD (method of Misra) activities. RESULTS: During statin therapy significant decrease of TC, LDL-C, TG was observed, both after 4 and 12 weeks, as compared with the initial values. All statins significantly decreased TBARS concentrations either 4 or 12 week therapy at all. The activities of antioxidants enzymes (CAT, GSH-Px, SOD) significantly increased after 4 weeks therapy in patients treated with atorvastatin and simvastatin. During pravastatin therapy it was noticed only increase of CAT activity after 12 weeks. CONCLUSION: In patients with dyslipidemia without clinical symptoms of atherosclerosis atorvastatin, simvastatin and pravastatin decreased similar TBARS concentrations in membrane in the isolated erythrocyte membranes. It was observed a significant increase of the antioxidant enzyme activities during atorvastatin and simvastatin treatment. Pravastatin therapy caused increase the CAT activity without any effect on the activities of GSH-Px and SOD.

[The comparison of simvastatin and atorvastatin effects on hemostatic parameters in patients with hyperlipidemia type II]. / Porównanie wplywu simwastatyny i atorwastatyny na wybrane parametry ukladu krzepniecia u chorych z hiperlipidemia typu II.

The studies results of statin influence on hemostasis are various. The aim of our study was to evaluate the effects of simvastatin and atorvastatin on hemostatic parameters, such as activity of factor X, antithrombin III, fibrinogen concentration and Lp(a). 72 patients (pts) aged 40-65 were involved in the study; 49 of them suffered from hyperlipidemia II (hlp II) with the initial concentration of total cholesterol (TC) >200 mg/dL, cholesterol LDL (LDL-C) >145 mg/dL, triglycerides (TG) <400 mg/dL. The control group consisted of 20 healthy persons. The pts with hlp II who underwent 4 weeks long lipid lowering diet were randomized into two groups: I--27 pts treated with simvastatin (20 mg/d), II--22 pts treated with atorvastatin (10 mg/d). The active statin therapy lasted 8 weeks. The activity of factor X and antithrombin III (AT III) was estimated by amidolytic methods, fibrinogen concentration (Fb) by the Clauss method, Lp(a)-immunoenzymatic method. The mean values of factor X activity and Fb serum concentration were higher in pts with hip II than in the control group, the AT III activity was lower. The Lp(a) concentration didn't differ between groups. Statin treatment was associated with significant reduction of factor X activity. Both simvastatin and atorvastatin markedly increased AT III (87%, 98%) in comparison to the initial values. No changes of Lp(a) concentration were observed during statin therapy. Atorvastatin therapy significantly increased the Fb concentration (12.3%). Simvastatin treatment didn't influence Fb concentration.

[Evaluation of thrombin generation and clot bound thrombin in plasma of hyperlipidemic patients treated with statins]. / Ocena stopnia generacji trombiny i wiazania trombiny ze skrzepem w osoczu ludzi z hiperlipidemia typu II leczonych statynami.

Thrombin is a crucial enzyme in blood coagulation cascade having both pro- and antithrombotic properties. Disorders of hemostatic balance increase possibility of clot formation and play significant role in the development of atherosclerosis. Statins applied in prevention of cardiovascular diseases, have not only hypolipemic activity but also many pleiotropic effects. The aim of this study was to evaluate the level of thrombin generation and clot bound thrombin in patients with hyperlipidemia type II (hlpII) before and after statins treatment. 81 patients were involved in this study: 59 patients with hlp II and 22 healthy. Patients with hlp II were treated with pravastatin (20 mg/day; n=10), simvastatin (20 mg/day; n=22), atorvastatin (10 mg/day; n=27). The treatment in each of groups lasted 8 weeks. Thrombin generation and clot bound thrombin level were estimated before and after therapy by means of spectrophotometric method with usage of chromogenic substrate S-2238. Our results demonstrate that therapy with atorva- simva- and pravastatin improves lipid levels in plasma and investigated hemostasis parameters. All three statins statistically significantly decrease total generated thrombin. Atorva- and simvastatin also significantly decrease activity both free generated thrombin and clot bound thrombin. No correlation between lipidogram and hemostatic parameters after treatment with statins suggests that observed changes are pleiotropic effect of statins treatment.

[Erythrocyte fluidity in patients with hyperlipidemia during statins therapy]. / Plynnosc blon erytrocytów u pacjentów z hiperlipidemia leczonych statynami.

UNLABELLED: The lipid composition of erythrocyte membrane is in a state of dynamic equilibrium with plasma lipoproteins and reflects the processes taking place in extracellular environment. The recent studies were devoted to the phenomenon of modification of atherosclerosis development by statins. The aim of the study was evaluation of three statins: simvastatin, atorvastatin and pravastatin on plasma lipidogram and fluidity of erythrocytes membranes in patients (pts) with hyperlipidemia (hlp) type II. INVESTIGATED GROUP: the study comprised 114 pts, including 94 pts with hlp type II without concomitant chronic diseases and 20 healthy volunteers. Pts were qualified to treatment with statins if their LDL-cholesterol concentration (LDL-C) was above 170 mg/dL (4,1 mmol/L), total cholesterol (TC) > 250 mg/dL (6,5 mmol/L) and triglicerydes (TG) < 400 mg/dL (4,5 mmol/L). Pts were randomised to three groups: group I-n = 31 pts treated with atorvastatin (10 mg/d); group Il-n = 31 with simvastatin (20 mg/d), group III-n = 32 with pravastatin (20 mg/d). METHODS: after 4 and 12 weeks of active treatment the following parameters were determined: TC, HDL-C, TG (by enzymatic method using BioMerieux tests); LDL-C was calculated from the Friedewald formula and erythrocyte membranes fluidity by electron paramagnetic resonance with two spin labels (5-DSA, 16-DSA). RESULTS: During statin therapy significant decrease of TC, LDL-C, TG was observed, both after 4 and 12 weeks, as compared with initial values. All statins after 4 weeks of therapy caused a significant increase of membrane fluidity in its surface layer at carbon 5 depth. The values of parameter S after 12 weeks did not differ significantly from the values in the control group. The percent decrease of membrane microviscosity at carbon 5 depth did not correlate significantly with percent changes plasma TC and LDL-C. Atorvastatin appeared to be the strongest drug liquidizing erythrocytes membranes. There were no significant changes in fluidity of membrane in its deeper layers (at carbon 16 level). CONCLUSION: Statins therapy was beneficial not only for modification of plasma lipids but caused the increase of erythrocytes membrane fluidity in the surface layer.

Damage to the structure of erythrocyte plasma membranes in patients with type-2 hypercholesterolemia.

BACKGROUND: Hypercholesterolemia may decrease the deformability of red blood cells which impairs their hemorheological behavior and promotes atherosclerosis. The study involved 60 hypercholesterolemic patients and 30 healthy individuals as the control group. METHODS: The membrane fluidity of erythrocytes was estimated by a spin-label method (5-doxylstearic acid (5-DSA)). The ratio of weakly to strongly (W/S) immobilized residues of erythrocyte membrane-bond maleimide-tempo spin label was studied in oxidative damage to membrane protein. Damage to erythrocyte proteins was also indicated by means of Na(+) K(+) ATPase activity. RESULTS: The membranes of hyperlipidemia (hlp) patients contain larger concentrations of cholesterol 2.16+/-0.24 than do those of the normolipemic individuals 0.31+/-0.24 (P<0.001). The level of Na(+) K(+) ATPase in the erythrocyte membrane from the control group was higher 103.4+/-1.3 (nmolPi/(mgproteinsh)) than in the patient group 93.6+/-3.2 (nmolPi/(mgproteinsh)) (P<0.001). The order parameter S 5-DSA in the control group was 0.745+/-0.009 and in hlp patients was 0.755+/-0.009 (P<0.001). The W/S ratio in the control group amounted to 2.00+/-0.09 and in the hlp patient group was 2.50+/-0.11 (P<0.001). CONCLUSION: Type-2 hypercholesterolemia causes changes in the structure and fluidity of erythrocyte plasma membranes since the excess of cholesterol affects the normal rheology of blood through its interaction with erythrocytes. It also impairs the function and structure of plasma membrane proteins.

Effects of simvastatin and pravastatin on peroxidation of erythrocyte plasma membrane lipids in patients with type 2 hypercholesterolemia.

Since hypercholesterolemia directly modifies the composition of erythrocytes plasma membrane, the influence of statins on erythrocytes has been researched. The beneficial effects of statins on clinical events may involve mechanisms that modify endothelial dysfunction, plaque stability, thrombus formation and inflammatory responses. The aim of the study was to evaluate the hypolipemic efficacy and effects of pravastatin and simvastatin on erythrocyte membrane fluidity and damage of erythrocytes in patients with type 2 hypercholesterolemia in comparison with a control group of healthy subjects. The study involved 53 patients affected by type 2 hypercholesterolemia (mean age, 53.3 +/- 10.3) with initial total serum cholesterol (TC) levels > 250 mg/dL, LDL-cholesterol (LDL-C) levels > 170 mg/dL, and triglycerides (TG) levels < 400 mg/dL. The control group consisted of 30 healthy individuals (mean age 56.9 +/- 6.3). Statins were given for 12 weeks. The dosages for oral administration of simvastatin and pravastatin were 20 mg/day. Laboratory tests were carried out before and after 4 and 12 weeks of the pharmacological treatment. The damage to plasma membrane of erythrocytes was measured on the basis of lipid peroxidation. The fluidity of plasma membrane of erythrocytes was determined by electron paramagnetic resonance (EPR) spectroscopy, using two spin labels: 5-DSA and 16-DSA. The cholesterol level in the membrane of red blood cells was estimated. Simvastatin and pravastatin reduced the total cholesterol concentration and LDL-cholesterol in plasma, as well as the cholesterol concentration in erythrocytes membranes. Hypercholesterolemia induced changes in the basic properties of human erythrocyte plasma membrane, including its fluidity and the intensity of lipid peroxidation. These results indicate that the simvastatin and pravastatin therapy reverses the alteration in the erythrocyte plasma membrane properties.

Increased oxidative stress in subjects exposed to carbon disulfide (CS2)--an occupational coronary risk factor.

There is considerable epidemiological evidence that workers exposed to carbon disulfide (CS2) develop premature atherosclerosis leading to increased rates of coronary heart disease (CHD), but mechanisms underlying this association remain obscure. The present study documents that occupational exposure to CS2 modifies the oxidative status of plasma, which is a major determinant of the susceptibility to atherosclerosis. Concentrations of thiobarbituric reactive substances (TBARS), which reflect lipid peroxidation processes in plasma, were determined in 29 men who were exposed to CS2 for more than 20 years, in 24 patients with peripheral atherosclerosis, and in 30 unexposed, healthy control subjects. TBARS concentrations were significantly increased both in CS2-exposed subjects and in patients with peripheral atherosclerosis. Subjects in both groups presented also with decreased levels of plasma alpha-tocopherol, a major plasma antioxidant. In addition, decreased activities of two enzymatic antioxidants, glutathion peroxidase and catalase, were noted both in CS2-exposed subjects and patients with peripheral atherosclerosis. Finally, LDL isolated from both groups showed increased susceptibility to transition metal-induced oxidation in vitro. It is concluded, that occupational exposure to CS2 produces oxidative stress in plasma. This may favor the development of atherosclerosis and increase the incidence of CHD in workers exposed to CS2.