Nontraditional risk factors in carotid artery disease.

Carotid atherosclerosis (AS) is one of the main risk factors for ischemic stroke. Our aim is to evaluate the nontraditional biochemical markers in asymptomatic and symptomatic patients with carotid artery plaque. This study was conducted on 55 patients: 43 with symptomatic and 12 with asymptomatic carotid artery disease. Lipoprotein (a) (Lp(a)), homocysteine, adiponectin, nitric oxide (NO), and tumor necrosis factor alpha (TNF-alpha) levels were measured in the plasma. The mean of total cholesterol, triglyceride, and homocysteine levels was significantly elevated in the symptomatic group as compared with the asymptomatic group (P = .03). In the asymptomatic group, adiponectin and NO levels showed elevations as compared with the symptomatic group but this increase was not significant (P > .05). Lipoprotein (a) and TNF-alpha levels acted inversely with adiponectin and NO. There was an insignificant decline in Lp(a) and TNF-alpha levels in the asymptomatic group as compared with the symptomatic group (P > .05).

Alterations in lipid peroxidation and antioxidant status in different types of intracranial tumors within their relative peritumoral tissues.

OBJECTIVES: Elevated levels of lipid peroxidation and changes in the concentration of enzymatic and non-enzymatic antioxidant systems have been reported in various cancers, but there are very few reports available of lipid peroxidation due to oxidative stress in patients with intracranial neoplasms. The purpose of this study was to assess alterations in lipid peroxidation and antioxidant status in different types of tumors and to compare the results with their relative peritumoral tissues and compare the oxidative status in different grades of tumors. PATIENTS AND METHODS: We investigated the extent of oxidative stress and the levels of antioxidants in 16 astrocytomas and 38 other different types intracranial tumors comparing the results with their corresponding peritumoral tissues and comparing the levels in between low-grade and high-grade tumors. The extent of lipid peroxidation as evidenced by the formation of thiobarbituric acid-reacting substances (TBARS), as well as the status of the antioxidant systems such as superoxide dismutase (SOD), glutathione reductase (GR) and reduced glutathione (GSH) in tumor tissues and adjacent peritumoral tissues was estimated. The tumoral tissues were also compared as to their degrees of malignancy. RESULTS: According to our results lipid peroxidation in brain tumor tissues was enhanced compared to the corresponding adjacent peritumoral tissues. This was accompanied by a significant tumoral decrease in both enzymatic and non-enzymatic antioxidants. The low levels of antioxidants in tumor tissues, might be related to an increased use of antioxidant systems to scavenge lipid peroxides. Also a striking elevation in TBARS levels, and decrease in SOD activity and GSH levels were seen in high-grade tumors when compared with low grades. CONCLUSION: These findings emphasize a consistent difference in the level of antioxidants between the tumoral sample and its corresponding peritumoral tissue, independently of the tumoral type, and the most pivotal action would seem to minimise exposure to endogenous and exogenous sources of oxidative stress.

Increased serum sialic acid levels in primary osteoarthritis and inactive rheumatoid arthritis.

Accumulation of oxidized proteins and impaired antioxidant system have been shown to be associated with arthritis. Serum sialic acid (SA) is known as a parameter of inflammation. In the present study, to explore the potential role of SA in arthritis, we measured serum SA levels, plasma protein oxidation, and antioxidant status in patients with primary osteoarthritis (POA) and inactive rheumatoid arthritis (RA). Inactive RA (iRA) was defined upon the American College of Rheumatology criteria for clinical remission of RA. A total of 40 patients (20 POA patients, including 4 male subjects, and 20 iRA female patients) and 20 healthy female subjects were included in this study. SA, antioxidants, and protein oxidation levels were determined spectrophotometrically in serum or plasma samples. Serum SA levels were significantly increased in POA (3.34 +/- 0.37 mM, p < 0.0001) and iRA (3.11 +/- 0.47 mM, p < 0.05), compared with healthy controls (2.41 +/- 0.16 mM). Plasma total antioxidant activity, plasma superoxide dismutase activity and serum reduced glutathione levels were significantly decreased in patients with POA and those with iRA, whereas plasma carbonyl content and serum total protein were increased in those patients. Moreover, plasma total thiol levels were significantly increased in iRA and decreased in POA. Thus, increased SA and protein oxidation levels are associated with the decreased antioxidant levels in POA and iRA patients. These results suggest that SA may be considered as a potent defense molecule against oxidative damage in arthritis. Antioxidant therapy may halt or ameliorate the progression of arthritis.

Preliminary study showing the relationship between platelet fibronectin, sialic acid, and ADP-induced aggregation levels in coronary heart disease.

Several studies indicate that thrombosis plays an important role in the pathogenesis of coronary heart disease (CHD). Fibronectin is a multifunctional protein in plasma, other body fluids, and cell surface and plays an important role in platelet functions, including mediation of cell-cell and cell-surface interactions. Sialic acid is a regular constituent of glycoproteins and gangliozides in the outer cell membrane of mammalian cells. Therefore, the sialic acid content of platelets, which are characterized by their ability to aggregate with each other, can be important in leading to thrombus formation. In this study, platelet fibronectin, sialic acid-, and adenosine diphosphate (ADP)-induced platelet aggregation levels were determined in patients with CHD. Platelet sialic acid concentrations were determined by Warren's method. Platelet aggregation tests with ADP in platelet-rich plasma (PRP) were analyzed by use of an aggregometer. Platelet homogenate fibronectin levels were determined by ELISA. Total protein levels were determined by Lowry method. Our results indicate that, in patients with no vessel disease (patients with no obstructed vessel but suffering from chest pain, like angina pectoris) platelet fibronectin levels were significantly lower than the total of the other patients (patients with 1, 2, or 3 obstructed coronary vessels) (p<0.05). Sialic acid levels in patients with no vessel disease were significantly lower than the total of the patient group (p<0.05). There was significant (+) correlation between platelet aggregation, platelet fibronectin, platelet sialic acid, and severity of disease (p<0.05). Our preliminary findings suggest that, especially platelet fibronectin levels potentially represent a pathogenic factor for CHD.

The Relationship Between Lipid Peroxidation and LDL Desialylation in Experimental Atherosclerosis.

ABSTRACT High serum total cholesterol concentration has been strongly connected with atherosclerosis in numerous studies. Being the main carrier of cholesterol in blood, low-density lipoprotein (LDL) is also the principal lipoprotein causing atherosclerosis. Sialic acids are a family of amino sugars that are commonly found as terminal oligosaccharide residues on glycoproteins and are sialylated on their apolipoprotein and glycolipid constituents. In several studies, it was demonstrated that LDL has a 2.5- to 5-fold lower content of sialic acid in patients with coronary artery disease compared with healthy subjects. The role of oxidatively modified LDL in the pathogenesis has been well documented. These studies have focused on modifications in the lipid and protein parts of LDL. But recently, desialylated LDL and its relation with the oxidation mechanisms have received attention in the pathogenesis of atherosclerosis and coronary artery disease (CAD). From these points, we have performed atheroma plaques in an experimental atherosclerosis model with rabbits and examined the LDL and plasma sialic acid and thiobarbituric acid reactive substance (TBARS) levels in the same model. We also have determined serum sialidase enzyme activities relevant with these parameters. LDL sialic acid levels were significantly decreased in the progression of the atherosclerosis (by the 30th, 60th, and 90th days). LDL and plasma TBARS levels and plasma sialidase enzyme activities were significantly elevated by the same time periods. In conclusion, serum sialidase enzyme may play an important role in the desialylation mechanism, and reactive oxygen substance (ROS) may affect this reaction.

Investigation of tissue factor and other hemostatic profiles in experimental hypothyroidism.

The influence of thyroid failure on hemostasis has been studied and is still not well understood. These patients have high risk for cardiovascular diseases because of the lipid metabolism and procoagulant agents. But the influence of thyroid failure on hemostasis is controversial. Tissue factor (TF) has an important role in the thromboembolic state. Recent experiments have demonstrated that TF-dependent activation of the coagulation cascade plays an important role in the pathophysiology of intravascular thrombus formation. The purpose of the present study was to investigate the contributions of TF, factor VII:C (FVII:C), factor XII:C (FXII:C), and fibrinogen in experimental hypothyroidism. TF was obtained from the thyroid gland and lung tissue of 10 rats following experimental hypothyroidism induced for 30 d and compared with similar tissue from 10 control rats. Significantly increased TF activities were found in hypothyroid rats. By contrast, FVII:C level was significantly decreased when compared with the control group. In this respect it is interesting to note that a hypercoagulable state due to increased thromboplastic activity may occur. Based on those results, elevated tissue factor activities (TFa) of the patients with low thyroid dysfunction may have another risk factor for cardiovascular diseases.

Comparison of platelet fibronectin, ADP-induced platelet aggregation and serum total nitric oxide (NOx) levels in angiographically determined coronary artery disease.

INTRODUCTION: Coronary thrombosis is an important determinant of prognosis in patients with acute coronary syndromes. Fibronectin is also found in platelets within the alpha secretory granules and secreted following platelet stimulation by a variety of agonist. Available data suggest that expression of platelet fibronectin on the cell surface may indicate a role in platelet aggregation and adhesion to fibrin thrombi and connective tissue. Clear evidence has emerged that a concerted action of nitric oxide (NO) generated by either endothelial or platelet NO synthases regulates platelet activation, causing inhibition of adhesion and aggregation. The aim of the present study was determining and correlating the serum total NO (NOx), platelet fibronectin and ADP-induced platelet aggregation levels in coronary artery disease (CAD) patient subgroups. MATERIALS AND METHODS: A total of 43 coronary artery disease patients were included in this study. Peripheral blood samples from patients with coronary artery disease were obtained from the Department of Cardiology. Platelet aggregation tests with adenosine diphosphate (ADP) were analyzed by using aggregometer. Platelet fibronectin concentrations were determined by enzyme-linked immunosorbent assay (ELISA). Serum total nitric oxide (NOx) levels were determined by colorimetric method. RESULTS: In patients with double-vessel disease, platelet fibronectin levels were found to be significantly higher than no-vessel disease (p<0.001), single-vessel disease (p<0.01) and triple-vessel disease (p<0.001). In addition, in patients with single-vessel disease platelet fibronectin levels significantly higher than no-vessel disease (p<0.05). We could not find any significant differences in ADP-induced platelet aggregation and serum NOx values between CAD patient subgroups. There was a positive correlation between platelet fibronectin levels and severity of disease (r=0.315, p<0.05).

Evaluation of fibronectin, vitronectin, and leptin levels in coronary artery disease: impacts on thrombosis and thrombolysis.

In this study, the levels of fibronectin, vitronectin, leptin, tissue plasminogen activator (t-PA), and lipid parameters were investigated in patients with coronary artery disease (CAD) and control group. The average plasma fibronectin levels in CAD patients group were significantly higher compared with the control group (p=0.006). Moreover, in patients with triple-vessel disease, plasma fibronectin levels were found to be significantly higher than those in the control group (p<0.05). Plasma vitronectin levels in patients with CAD were found to be significantly higher than those in the control group (p=0.000). In addition, in patients with double vessel disease plasma vitronectin levels were significantly higher than no vessel disease and control group, triple vessel disease was significantly higher as compared with no vessel disease, single vessel disease, and control group (p<0.05). We could not find any significant differences in t-PA values between CAD patients and control group. On the other hand, the average leptin levels in the group of patients were higher than those in the control group but there were no statistically significant differences found between them (p>0.05) because of high SD values. There was strong (+) correlation between fibronectin, vitronectin, and severity of disease [vitronectin/severity of disease, r = 0.5074 (p = 0.000), fibronectin/severity of disease, r = 0.2971 (p = 0.007)]. In conclusion, we can say that fibronectin and vitronectin have become greatly important in pathogenesis of coronary artery disease. High leptin levels may be contribute to platelet aggregation in patients with coronary artery disease. But, elevated serum levels of leptin cannot be useful diagnostic and monitoring markers in patients with coronary artery disease.

The relationship of TFPI, Lp(a), and oxidized LDL antibody levels in patients with coronary artery disease.

OBJECTIVES: The aim of the present study was to determine and correlate tissue factor pathway inhibitor (TFPI), lipoprotein (a) (Lp(a)), oxidized low-density lipoprotein (LDL) antibody (oLAB), and thiobarbituric acid reactive substances (TBARS; as a marker of lipid peroxidation) levels in patients with coronary artery disease (CAD) and in a control group. DESIGN AND METHODS: Peripheral blood samples from patients with coronary heart disease were provided by the Department of Cardiology. Serum oLAB, Lp(a), plasma total TFPI, and plasma-free TFPI levels were determined by ELISA. Serum TBARS levels were determined by a spectrophotometric method using thiobarbituric acid. RESULTS: The CAD and the control group were matched for age and sex. Serum Lp(a), oLAB, and plasma total TFPI levels in patients with coronary heart disease were found to be significantly higher than in the control group (P < 0.001). But there was no difference in plasma-free TFPI levels between patients with CAD and the control group (P > 0.05). In patients with single (P < 0.05), double, and triple vessel (P < 0.01) disease, the mean serum Lp(a) levels were significantly higher than in the control group. On the other hand, in patients with single vessel disease (P < 0.05), double vessel disease (P < 0.05), and triple vessel disease (P < 0.001), plasma total TFPI levels were found to be significantly higher than in the control group. We also found a significant positive correlation (r = 0.28, P < 0.05) between serum Lp(a) and plasma total TFPI levels in CAD. In the patient group, TBARS, total cholesterol, triglyceride (TRG), and LDL cholesterol levels were found to be significantly higher than those in the control group. In addition, high-density lipoprotein (HDL) cholesterol levels were found to be significantly lower than the control group. CONCLUSIONS: These results suggest that elevated plasma levels of total TFPI, Lp(a), and oLAB may be useful diagnostic and monitoring markers in patients with CAD.

Effects of melatonin on plasma S-nitrosoglutathione and glutathione in streptozotocin-treated rats.

The aim of this study was to determine the effects of streptozotocin-induced diabetes on plasma reduced glutathione (GSH) and S-nitrosoglutathione (GSNO) levels. Further, the study investigated whether an antioxidant, pineal hormone melatonin, could protect against STZ-induced effects. STZ significantly decreased plasma GSH but increased the levels of plasma GSNO. Daily supplementation with melatonin restored plasma thiol to control values. Data suggest that STZ-induced hyperglycemia and compounds that act as scavengers of free radicals and peroxynitrite like melatonin may exert protection against STZ-induced toxicity.

Curcumin's effects on sialic acid level and sialidase activity in Ehrlich ascites tumor bearing mice.

In this study, we determined curcumin's anticancer and chemopreventive effects in mice bearing Ehrlich ascites tumor by evaluation of cancer biomarkers, sialic acid level and sialidase activity. Both plasma sialic acid level and sialidase activity increased significantly in the mice group with Ehrlich ascites tumor. When the tumor groups fed with curcumin and fed with sesame oil were compared, sialic acid level and sialidase activity in ascites fluid significantly reduced in the group fed with curcumin in addition to the increases of plasma sialic acid level and sialidase activity. The tumor group fed with curcumin lived twice longer than the one fed with sesame oil. Curcumin as a phenolic compound decreased all these parameters in Ehrlich ascites tumors and lengthened survival by 88% in the mice with tumor. We concluded that curcumin has anticancer activity.

Vitamin E supplementation in streptozotocin-treated rats alters cerebellar and plasma nitric oxide metabolism.

Nitric oxide (NO) free radicals appear to contribute to the pathogenesis of a number of disorders including diabetes mellitus. The aim of this study was to determine the effects of streptozotocin (STZ)-induced diabetes on nitric oxide (NO) metabolites in plasma and cerebellar nitric oxide synthase (NOS) activity. Further, it was of interest to determine whether an antioxidant, vitamin E, could reverse the STZ-induced effects. STZ significantly decreased cerebellar NOS but increased the level of plasma total nitrite + nitrate and the level of plasma nitrate. Supplementation with vitamin E effectively reduced the STZ-induced effects. Data demonstrate that vitamin E may serve as a protective antioxidant in STZ-induced diabetes.

Plasma vitronectin levels in patients with coronary atherosclerosis are increased and correlate with extent of disease.

BACKGROUND: Acute thrombosis after atherosclerotic plaques disruption is a major complication of primary atherosclerosis, leading to acute ischemic syndromes and atherosclerotic progression. Vitronectin (VN) is multifunctional glycoprotein in blood and in the extracellular matrix. It binds glycosaminoglycans, collagen, plasminogen and urokinase receptor. VN stabilizes the inhibitory confirmation of plasminogen activation inhibitor-1 (PAI-1). Vitronectin may control the clearance of vascular thrombi by binding and stabilizing PAI-1, a key regulator of fibrinolysis. Therefore, VN is generally regarded as a cofactor for PAI-1 activity. On the other hand vitronectin binds to platelet glycoproteins may mediate platelet adhesion and aggregation at sites of vascular injury. Previous studies showed that anti-VN antibodies inhibit platelet aggregation in vitro, suggesting that vitronectin contributes to platelet accumulation at sites of vascular injury. In this study; we investigated the levels of plasma vitronectin in patients with Coronary Artery Disease (CAD) and control group. METHODS: The patient group was divided into four subgroups: patients with no, single, double and triple vessel disease according to their angiography results. ELISA procedure (Technoclone) was used to determine the plasma vitronectin levels. RESULTS: Plasma vitronectin levels in patient with CAD (% 125.87 +/- 58.38) were found to be significantly higher than control group (% 89.47 +/- 25.3) (p:0.000). In addition, in patients with double vessel disease (% 146.03 +/- 71.69) plasma vitronectin levels were significantly higher than no vessel disease (% 87.84 +/- 22.30) and control group, triple vessel disease (% 160.81 +/- 57.02) significantly higher as compare with no, single vessel disease (% 111.68 +/- 45.34) and control group (p < 0.05). There was no correlation between vitronectin and lipid parameters. CONCLUSION: These findings suggested that vitronectin is a marker of CAD. Elevated levels may indicate its role in the genesis and/or progression of CAD or may be the results of a compensatory mechanism.

Looking for Our Ten Years Results for Coronary Heart Disease and Ischemic Stroke Group for the Standpoint of Haemostasis.

To evaluate the role the coagulation and fibrinolysis abnormalities in the pathogenesis of ischemic stroke of undetermined etiology, we assayed plasma concentration of fibrinopeptide-A and thrombin-antithrombin III complex, both sensitive markers for thrombin activation and fibrin formation, and D-dimer, a marker of plasmin activity and fibrinolysis. Hemostatic markers were measured in 32 patients with acute stroke and 20 patients with chronic stroke, and compared with 21 normal subjects. Fibrinopeptid-A and thrombin-antithrombin III complex levels were not elevated significantly, whereas the D-dimer level was markedly raised in acute (p<< 0.001) and chronic (p< 0.05) phases of ischemic stroke in comparison with the control group. Prolonged elevation of D-dimer concentration suggests that hemostatic abnormalities have a primary role in the pathogenesis of ischemic stroke. The measurement of D-dimer concentration may help to better decide the indications for therapy of the patients with ischemic stroke of undetermined etiology.