A comparative analysis of normodipin and spirapril effects on intravascular activity of platelets in patients with metabolic syndrome

AIM: To study effects of two hypotensive drugs--normodipin and spirapril--on intravascular activity of platelets in patients with metabolic syndrome (MS). MATERIAL AND METHODS: Normodipin was given to 25 patients with MS for 3 months, spirapril--to 20 patients for 3 months. The effect was evaluated by changes in lipid peroxidation in plasm and platelets, antioxidant defense of liquid blood and platelets, intravascular activity of platelets. RESULTS: Administration of normodipin in MS patients had a positive effect on lipid peroxidation and normalized intravascular activity of platelets. Such pronounced positive effects on lipid peroxidation of plasm and platelets as well as on intravascular activity of the latter were not registered after use of spirapril. CONCLUSION: Optimization of platelet function in MS patients can be achieved with long-term normodipin treatment.     

Correction of primary hemostasis in patients suffering from arterial hypertension with metabolic syndrome

The purpose of the study was to compare the effectiveness of normodipin and nebivolol for correction of platelet dysfunction in patients with metabolic syndrome. Normodipin was administered to 25 patients during three months in a dose of 10 mg a day. Nebivolol was administered to 21 patients in a dose of 5 mg a day. The dynamics of anthropometric indices, lipid blood spectrum, lipid peroxidation in the plasma and platelets, the antioxidant protection of the liquid part of blood and platelets, and aggregative platelet activity were evaluated. The results were processed using Student's criteria and system multi-factor analysis. The use of normodipin effected peroxidation syndrome more positively, and optimized platelet function to a greater extent that nebivolol. Long-term administration of normodipin is able to stabilize the achieved effect. To lower body weight in patients with arterial hypertension with metabolic syndrome normodipin application should be combined with non-drug treatment.     

Effect of amlodipine on intravascular thrombocyte activity in patients with arterial hypertension and metabolic syndrome

In order to evaluate therapeutic effects of amlodipine on intravascular thrombocyte activity (ITA) in patients having arterial hypertension (AH) with metabolic syndrome (MS), 20 patients were treated with amlodipine for 1 month. The researchers monitored changes in anthropometric indices, blood lipid spectrum, lipid peroxidation in serum and thrombocytes, anti-oxidant protectability of platelets and the liquid part of blood and ITA. Amlodipine application in patients having AH with MS reduced peroxidation syndrome and optimized thrombocyte aggregation. Long-term administration of amlodipine stabilizes the achieved effect. To lower body weight in patients having AH with MS administration of amlodipine should be combined with use of non-drug means.     

Losartan for the correction of thrombocyte activity in patients suffering from arterial hypertension with metabolic syndrome

The aim of the study was to evaluate therapeutic effects of losartan on intravascular thrombocyte activity (ITA) in patients suffering from arterial hypertension with metabolic syndrome (MS). The subjects of the study were 35 patients administered losartan 50 mg a day for 4 months. The dynamics of the following parameters were evaluated: anthropometric parameters, blood lipids, lipid peroxidation in blood plasma and thrombocytes, the anti-oxidative protection of the liquid part of blood and platelets, and ITA. Student criterion was used for statistical analysis. In patients with AH and MS losartan had a positive effect on peroxidation syndrome and optimized ITA. To maintain the positive effects, prolonged administration of losartan is needed. In order to lower body mass in AH patients with MS losartan should be used in combination with non-drug means.     

Thrombocytic hemostasis in hypertensive patients with metabolic syndrome and its correction with lovastatin

The objective of the study was to evaluate the efficiency of lovastatin correction of dyslipidemia and impaired intravascular platelet activity (IPA) in patients with arterial hypertension (AH) concurrent with metabolic syndrome (MS). Eighteen patients were given lovastatin for a month. The time course of changes in anthropometric parameters, blood lipid spectrum, plasma and lipid peroxidation, antioxidative protectiveness of the liquid blood part and platelets, and IPA were assessed. The results were processed by Student's test and correlation analysis. Lovastin was ascertained to correct dyslipoproteinemia and peroxidation syndrome and to optimize the intrathrombocytic mechanisms responsible for their function regulation in patients with AH + MS. Lovastatin inhibits in vivo increased platelet activity. These effects may be stabilized during its use. Body weight loss and diminished insulin resistance in patients with AH concurrent MS require long use of lovastatin along with low-calorie diet and exercises.     

Non-pharmacological correction of impaired platelet hemostasis in hypertensive patients with metabolic syndrome

Low-calorie diet and individually adjusted physical exercise used in combination in hypertensive patients with metabolic syndrome correct shifts in blood lipid spectrum, relieve peroxidation syndrome, normalize impaired platelet hemostasis, suppress enhanced adhesive and aggregation functions of platelets in vitro and their intravascular activity. The improvement reached maximum after 24 weeks of treatment but control values were not achieved. Therefore, for effective correction of metabolic processes and platelet hemostasis in hypertensive patients with disorder of glucose tolerance, non-pharmacological measures should be supplemented with pharmacological ones.     

Effect of lovastatin on adhesive and aggregation function of platelets in patients with arterial hypertension and dislipidemia

The aim of the study was to evaluate efficiency of correction of lipid profile disturbances and platelet dysfunction by lovastatin in patients with arterial hypertension and dyslipidemia. Lovastatin was given to 29 patients for 4 months. The main parameters measured included dynamics of blood lipid profile, lipid peroxidation in plasma and platelets, antioxidative protection of blood fluid and platelets, platelet activity. t-Students test was used to assess statistical significance of the results. It was shown that lovastatin has beneficial effect on dyslipoproteidemia and peroxidation syndrome. Moreover, it normalizes intraplatelet regulatory mechanisms and inhibits enhanced platelet activity. Effects of lovastatin in patients with arterial hypertension and dyslipidemia persist under conditions of long-term therapy.     

Primary hemostasis activity in patients with arterial hypertension and impaired glucose tolerance treated with trandolapril

The study was designed to evaluate effect of trandolapril, an ACE inhibitor, on platelet aggregation in patients with arterial hypertension and impaired glucose tolerance. The drug was given to 38 patients for 12 weeks. The key end points were dynamics of the blood lipid spectrum, lipid peroxidation in plasma and platelets, antioxidative protection of the blood's liquid medium and platelets, platelet aggregation. The data obtained were treated using Student's t-test. They show that trandolapril exerts positive effect on peroxidation syndrome and reduces platelet aggregation.     

The influence of nebivolol on thrombocyte aggregation in patients with arterial hypertension with metabolic sydrome

The research was undertaken with the purpose to assess the efficiency of nebivolol for correction of thrombocyte aggregation capability in patients having arterial hypertension (AH) with metabolic syndrome (MS). 21 patients were administered nebivolol in a dose of 5 mg per day for a month. The dynamic changes in the following parameters were evaluated: anthropometric measurements, blood lipid spectrum, lipid peroxidation in serum and thrombocytes, antioxidative protectability of the liquid part of blood and platelets, thrombocyte aggregation activity. The results were processed using Student criterion and system multifactoral analysis. Nebivolol reduced peroxidation syndrome and optimized thrombocyte aggregation in patients with AH and MS. When administered for a long period of time, nebivolol is able to stabilize the achieved effect. Combining nebivolol application with use of non-drug means is necessary to reduce body weight in patients having AH with MS.     

Correction of thrombocyte-vascular hemostasis in metabolic syndrome

The purpose of the study was to evaluate the therapeutic effects of lovastatin and allicor on thrombocyte-vascular hemostasis in patients suffering from arterial hypertension (AH) with metabolic syndrome (MS). Twenty-two patients were administered lovastatin in a dose of 20 mg before sleep; 23 patients received allicor in a dose of two tablets or 150 mg twice a day. The therapy lasted one month in both groups. The dynamics of the following variables was evaluated: anthropometric parameters, blood lipid spectrum, lipid peroxidation in serum and thrombocytes, the antioxidative protectability of the lipid part of blood and thrombocytes, thrombocyte aggregation and their intravascular activity, and vascular hemostasis indices. The results were processed using Student coefficient, as well as system and correlation analysis. The study shows that lovastatin and, to a less degree, allicor, has a hypolipidemic effect, as well as a positive effect on peroxidation syndrome in patients suffering from AH with MS, optimizing thrombocyte-vascular hemostasis to the same degree. As a cheaper drug, allicor may be used widely to prevent thrombosis in patients with AH with MS. In order to lessen body mass in such patients, lovastatin and allicor should be applied together with non-drug means.     

Comparative evaluation of the influence of sulfhydryl and phosphate ACE inhibitors on thrombocyte aggregation in patients suffering from atrerial hypertension with metabolic syndrome

The purpose of the study was to compare the influence of two ACE inhibitors--captopril, a sulfhydryl one, and fozinopril, a phosphate one--on the aggregation activity of thrombocytes in patients suffering from arterial hypertension (AH) with metabolic syndrome (MS). Sixty-nine patients suffering from AH with MS were examined; 36 patients were administered captopril during 16 weeks, while 33 patients were treated with fozinopril during the same period of time. Changes in anthropometric parameters, blood lipid spectrum, lipid peroxidation in blood plasma and thrombocytes, and the antioxidative protection of liquid part of blood and platelets, as well as the aggregation activity of thrombocytes were assessed. The data received were processed using Student criterion and system multifactor analysis. The study shows that the use of fozinopril in patients with AH and metabolic syndrome attenuates peroxidation syndrome and optimizes thrombocyte aggregation. Prolonged fozinopril application will stabilize the achieved effect. Captopril did not have a positive effect on the parameters under study. In conclusion, fozinopril should be applied in combination with non-drug means to lower body weight in patients suffering from AH with MS.     

Effect of irbesartan of the function of hemocoagulative component of hemostasis in patients with arterial hypertension during metabolic syndrome

The aim of the study was to assess effects of irbesartan on disturbed platelet hemostasis in patients with arterial hypertension and metabolic syndrome. 38 patients received this drug for 16 weeks. Dynamics of lipid peroxidation in plasma and platelets, antioxidative protection of liquid blood fraction and platelets were estimated. The data were treated by the Student's t-test. Therapy with irbesartan for 4 months improved lipid peroxidation and primary hemostasis. Its continuation following the same regimen is expected to strengthen the obtained effect.     

Vitamin E. An inhibitor of the platelet release reaction.

Formation of lipid peroxides rises sharply when platelets undergo the release reaction. In this study the in vitro effect of vitamin E on platelet aggregation was investigated. alpha-Tocopherol, an anitoxidant of known inhibitory action on lipid peroxidation, was added to platelet suspensions in concentrations up to 1.5 mM. A dose-dependent reduction in platelet aggregation was observed, with complete inhibition of the secondary wave of aggregation at greater than or equal to 0.9 mM alpha-tocopherol. The inhibitory effect of alpha-tocopherol on the platelet release reaction was further documented by the decrease in aggregation-induced release of [14C]5-hydroxytryptamine from prelabeled platelets and by the reduction of N-acetylglucosaminidase activity released into the medium. The sharp rise in lipid peroxides normally associated with platelet aggregation was markedly reduced by alpha-tocopherol and also by acetylsalicylic acid, a known inhibitor of the platelet release reaction. In vivo studies examined the effect of oral vitamin E administration (1,200-2,400 IU daily) on plasma and platelet levels of alpha-tocopherol. Up to 1,800 IU daily, increasing dosages of vitamin E resulted in increasing concentrations of alpha-tocopherol in plasma and platelets, but intake of vitamin E in excess of this dosage failed to show any further increase in plasma or platelet levels.     

Oxidative stress of platelets and thrombocytopenia in patients with vivax malaria.

Oxidative stress and antioxidative capacity of platelets and the relationship with thrombocytopenia were determined in patients with vivax malaria and compared with those of healthy subjects. Whole blood thrombocyte count, platelet superoxide dismutase and glutathione peroxidase activities of patients with vivax malaria were lower and platelet lipid peroxidation levels were higher in patients than those of healthy subjects. There was an important negative correlation between whole blood thrombocyte count and platelet lipid peroxidation level. The antioxidative mechanisms of thrombocytes were insufficient in malaria patients and caused oxidative stress. The oxidative damage of thrombocytes might be important in the ethiopathogenesis of thrombocytopenia occurring in malaria.     

The influence of hypocaloric diet on thrombocyte rheology in patients with metabolic syndrome

The purpose of the study was to investigate the effects of hypocaloric diet (HCD) on intravascular thrombocyte activity (ITA) dynamics in patients with arterial hypertension (AH), androidal type of obesity, and glucose tolerance disorder. The subjects were 25 middle age patients with AH with metabolic syndrome (MS). Anthropometric variables, plasmatic lipid indices, as well as the intensity of lipid peroxidation in blood plasma and thrombocytes, were measured and evaluated. The patients' condition was being corrected using HCD during 24 weeks. The use of HCD in patients suffering from AH with metabolic syndrome favored lowering of the blood lipid spectrum shifts, suppression of peroxidation syndrome, and improvement of plasmatic and thrombocyte parameters. HCD lowered ITA, which was especially prominent by the end of the 24th week, but the control values were not reached. HCD in not effective enough as a sole method of correcting metabolic processes and ITA in patients suffering from AH with MS. Other therapeutic approaches to treatment of such patients should be searched.     

天麻钩藤饮对高血压病患者血压及血清过氧化氢酶的影响

目的 :观察天麻钩藤饮对肝阳上亢型高血压病患者血压及其抗氧化酶系统的影响。方法 :选择肝阳上亢型高血压患者 6 0例 ,随机分为天麻钩藤饮组 (中药组 )和非洛地平组 (西药组 )各 30例 ,治疗 4周 ,分别检测治疗前后患者血压和血清过氧化氢酶 (CAT)的活力变化。结果 :治疗后 ,2组血压均明显下降 ,组间比较差异无显著性 (P >0 .0 5 ) ,而中药组CAT的升高却较西药组明显 (t=15 .94 ,P <0 .0 1)。结论 :天麻钩藤饮对肝阳上亢型高血压病患者具有良好降压效果 ,并且能增加CAT活力 ,清除过多的氧自由基 ,防止血管内皮细胞的脂质过氧化。     

Clinical efficacy of combined therapy with enalapril + trimetazidine in patients with hypertension comorbid with ischemic heart disease and metabolic disturbances

AIM: To compare hypotensive and antiischemic efficacy of enalapril combination with trimetazidine or placebo, effects on plasmic lipid spectrum and membrane-cell parameters of erythrocytes and platelets in hypertensive patients with ischemic heart disease (IHD) in the presence of metabolic disturbances. MATERIAL AND METHODS: A randomized placebo-controlled comparative trial included 64 patients (mean age 55.60 +/- 0.52 years) with hypertension stage I-III, IHD (stable effort angina FC II-III, obesity of the first-third degree, diabetes mellitus type 2. The patients were divided into two groups matched by gender, age, duration of the disease, office blood pressure (OBP), functional class (FC) of effort angina, body mass index, glucose levels in the blood. 43 patients of group 1 received enalapril and trimetazidine. 21 patients of group 2 were treated with enalapril and placebo. The efficacy of the treatment was assessed by changes in the 24-h profile of BP and ECG, blood lipid spectrum and membrane-cell parameters. RESULTS: A significant fall was seen in systolic blood pressure of both groups patients. In group 1 there was an additional lowering of temporal index of systolic pressure, nocturnal diastolic, mean 24-h diastolic, mean 24-h blood pressure, double product of ischemic episodes, total cholesterol, dienic conjugates in platelets. Catalase activity in erythrocytes rose. CONCLUSION: An antiischemic effect of the therapy in stabilization of blood pressure, normalization of plasmic lipids and lipoperoxidase in erythrocytic and platelet membranes under multidirectional correlations between clinical and biochemical parameters point to different mechanisms of ischemic correction in enalapril and trimetazidine.     

Effects of tanakan on blood lipid peroxidation and platelet aggregation properties in patients with insulin-dependent diabetes mellitus

AIM: To elucidate tanakan effects on lipid peroxidation (LPO) products in blood serum, red cell and platelet membranes of patients with insulin-dependent diabetes mellitus (IDDM) with and without vascular complications. MATERIALS AND METHODS: Twenty-seven diabetics and 15 donors were examined. Platelet aggregation, malonic dialdehyde (MDA), hemoglobin (including glycosylated), blood total cholesterol and lipoproteins were measured routinely. RESULTS: Elevated levels of malonic dialdehyde (MDA) in the serum and red cell membrane in IDDM patients diminished in response to 6-week treatment with tanakan. Basal and induced MDA in platelets reduced, more noticeably in patients without angiopathy. Platelets resumed sensitivity to low-dose ristomycin. A 6-week course of tanakan failed to normalize platelet function completely. Moreover, platelets sensitivity to some inductors (ADP, adrenalin) enhanced, more noticeable in patients without angiopathy. CONCLUSION: Tanakan in IDDM shows properties of an effective antioxidant and return to normal LPO products level both in blood serum and red cell membrane. This eradicates a damaging action of free radical products in blood cells and endothelium. It is suggested that for normalization of platelet aggregation in IDDM a longer tanakan course is required or combined use of tanakan with other antithrombotic medicines of different mechanism of action may be effective.     

Effect of L-carnitine on acetyl-CoA content and activity of blood platelets in healthy and diabetic persons

BACKGROUND: Excessive blood platelet activity contributes to vascular complications in diabetic persons. Increased acetyl-CoA in platelets from diabetic persons has been suggested to be a cause of this hyperactivity. We therefore investigated whether L-carnitine, which up-regulates metabolism of acetyl-CoA in muscles and brain, may affect platelet function in healthy and diabetic individuals. METHODS: We obtained platelets from healthy and diabetic persons and measured acetyl-CoA concentrations, malonyl dialdehyde (MDA) synthesis, and platelet aggregation in the absence and presence of L-carnitine. Activities of selected enzymes involved in glucose and acetyl-CoA metabolism were also assessed. RESULTS: Fasting glucose, fructosamine, and hemoglobin A1c were present in significantly higher amounts in the blood of diabetic patients than in healthy individuals. Activities of carnitine acetyltransferase, glucose-6-phosphate dehydrogenase, oxoglutarate dehydrogenase, and fatty acid synthase were 17%-62% higher in platelets from diabetic patients. Mitochondrial acetyl-CoA was increased by 98% in platelets from diabetic patients, MDA synthesis was increased by 73%, and platelet aggregation by 60%. L-Carnitine had no or only a slight effect on these indices in platelets from healthy individuals, but in platelets from diabetic patients, L-carnitine caused a 99% increase in acetyl-CoA in the cytoplasmic compartment along with increases in MDA synthesis and platelet aggregation. CONCLUSIONS: Excessive platelet activity in persons with diabetes may result from increased acetyl-CoA, which apparently increases synthesis of lipid activators of platelet function. L-Carnitine may aggravate platelet hyperactivity in diabetic persons by increasing the provision of surplus acetyl-CoA to the cytoplasmic compartment.     

Heterogeneity of human platelets: V. Differences in glycolytic and related enzymes with possible relation to platelet age

Human platelets were separated by desity-centrifugation into heavy and light populations. Heavy platelets have an average volume approximately twofold greater than light platelets, and have previously been shown to be young platelets.All 11 enzymes of the Embden-Meyerhof pathway plus the five related enzymes: phosphoglucomutase, glucose-6-P dehydrogenase, 6-P-gluconic dehydrogenase, alpha-glycerol-P dehydrogenase, and glutathione reductase (TPNH) were examined in cell lysates from total, heavy, and light platelet populations. Apparent Km for individual enzymes were measured in a total platelet population. Empirical V(max) of the individual enzymes were measured in total, heavy, and light platelet populations. The three apparent rate-limiting enzymes for glycolysis were hexokinase, phosphofructokinase, and glyceraldehyde-3-P dehydrogenase.Heavy platelets contained approximately twofold greater enzyme activity (per gram wet weight) than light platelets for 7 of the 16 enzymes measured: hexokinase, phosphohexoisomerase, phosphofructokinase, glyceraldehyde-3-P dehydrogenase, phosphoglycerokinase, lactic dehydrogenase, and phosphoglucomutase. Heavy platelets also contained 1.9-fold greater reduced glutathione (GSH), 1.7-fold greater DPNH, and 1.2-fold greater TPNH than light platelets. Heavy platelets contained 1.8-fold less lipid peroxidation products (malonyl aldehyde equivalents) than light platelets and were 2.4-fold more resistant to lipid peroxidation catalyzed by 0.1 mM FeCl(3).Sterile incubation of heavy platelets, in vitro for 17 hr, resulted in a significant loss of enzyme activity for the "elevated" seven enzymes when compared with the remainder. Reducing agents such as GSH (0.1 mM), ascorbic acid (0.1 mM), and dithiothreitol (0.01 mM), when added to the incubation mixture, significantly reduced the in vitro loss of activity. In vitro incubation was also associated with a significant loss of GSH and DPNH and a 1.8-fold increase in lipid peroxidation products.