ascorbic-acid and Thrombosis

The analysis of the literature on communication of a hemostasis and vitamin C has allowed to assert, that its deficiency accelerates lipid peroxidation and reduces potential at porpoises, and it conducts to activation platelets, to acceleration of continuous intravascular blood coagulation of and to reduction in tolerance to thrombin. High dozes of vitamin C influences a hemostasis strengthens lipid peroxidation similarly to prooxidizers. Entering high dozes of vitamin C at the statuses menacing weith thromboses, it is desirable to supervise a level of markers of intravascular blood coagulation in plasma.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Blood Coagulation; Blood Platelets; Disseminated Intravascular Coagulation; Homeostasis; Humans; Lipid Peroxidation; Platelet Activation; Thrombin; Thrombosis

Topics: Aged; Animals; Arteriosclerosis; Ascorbic Acid; Avitaminosis; Calcium; Humans; Lipid Metabolism; Thrombosis; Vitamin A; Vitamin B Complex; Vitamin E; Vitamin K; Vitamins

Topics: Animals; Anterior Chamber; Aqueous Humor; Ascorbic Acid; Blood Pressure; Cataract; Child; Cryosurgery; Diabetes Complications; Glaucoma; Gonioscopy; Humans; Intraocular Pressure; Microsurgery; Miotics; Ophthalmodynamometry; Sclera; Thrombosis; Tonometry, Ocular; Uveitis, Anterior; Visual Field Tests

Hypoglycemia produces thrombosis activation, but little attention has been paid to the effects of hyperglycemia following recovery from hypoglycemia on thrombosis activation.. In both twenty-two healthy subjects and twenty-one matched persons with type 1 diabetes, recovery from a 2-h induced hypoglycemia was obtained by reaching normo-glycemia or hyperglycemia for another 2 h. After this, normal glycemia was maintained for the following 6 h. Hyperglycemia after hypoglycemia was also repeated with the concomitant infusion of vitamin C. In both controls and people with diabetes, the recovery with normo-glycemia was accompanied by a significant improvement of Von Willebrand factor (vWF), prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin III-complexes (TAT), P-selectin, plasminogen activator inhibitor-1 (PAI-1), nitrotyrosine and 8-iso-prostaglandin F2α (8-iso-PGF2α) (p < 0.01 vs hypoglycemia for all the parameters), all directly affected by hypoglycemia itself (p < 0.01 vs baseline for all the parameters). On the contrary, the recovery with hyperglycemia after hypoglycemia worsens all these parameters (p < 0.01 vs normoglycemia for all the parameters), an effect persisting even after the additional 6 h of normo-glycemia. The effect of hyperglycemia following hypoglycemia was partially counterbalanced when vitamin C was infused (p < 0.01 vs hyperglycemia alone for all the parameters), suggesting that hyperglycemia following hypoglycemia may activate thrombosis through the oxidative stress production.. This study shows that, in type 1 diabetes as well as in controls, the way in which recovery from hypoglycemia takes place could play an important role in favoring the activation of thrombosis and oxidative stress, widely recognized cardiovascular risk factors.

Topics: Adult; Antithrombin III; Ascorbic Acid; Blood Glucose; Diabetes Mellitus, Type 1; Dinoprost; Endothelium, Vascular; Female; Healthy Volunteers; Humans; Hyperglycemia; Hypoglycemia; Male; Oxidative Stress; P-Selectin; Peptide Fragments; Peptide Hydrolases; Plasminogen Activator Inhibitor 1; Protein Precursors; Prothrombin; Thrombosis; von Willebrand Factor; Young Adult

Elevated plasma homocysteine levels are associated with the risk of atherosclerosis and arterial and venous thrombosis. We have previously demonstrated that rabbits rendered hyperhomocysteinemic by parenteral administration of homocysteine develop a dysfibrinogenemia that is associated with the formation of fibrin clots that are abnormally resistant to fibrinolysis. We suggested that this acquired dysfibrinogenemia contributes to the thrombotic tendency in hyperhomocysteinemia. However, it was possible that the homocysteine-associated dysfibrinogenemia was an artifact of the parenteral administration model. Therefore, the goals of the current study were to develop a diet-induced model of homocysteinemia in rabbits and determine whether a dysfibrinogenemia and evidence of oxidative stress develop in this model as they do when homocysteine is injected. We found that rabbits fed a diet severely deficient in folate and mildly deficient in choline develop mild hyperhomocysteinemia: 14.8+/-4.0 microM in deficient rabbits compared to 9.0+/-1.7 microM in controls. The deficient rabbits also develop evidence of oxidant stress: increased lipid peroxidation in liver, impaired mitochondrial enzyme activities in liver and elevated caspase-3 levels in plasma. Most importantly, the deficient rabbits also develop a dysfibrinogenemia characterized by increased resistance to fibrinolysis. We believe that this dietary model of homocysteinemia is clinically relevant and reproduces many features associated with hyperhomocysteinemia in previous work using in vitro and in vivo models. Our findings suggest that an acquired dysfibrinogenemia could play a role in the increased risk of atherothrombotic disease in mildly hyperhomocysteinemic human subjects.

Topics: Animals; Antioxidants; Ascorbic Acid; Caspase 3; Choline Deficiency; Diet; Disease Models, Animal; Female; Fibrinolysis; Folic Acid Deficiency; Homocysteine; Hyperhomocysteinemia; Mitochondria; Oxidative Stress; Rabbits; Risk Factors; Thrombosis; Vitamin E

Smoking is associated with endothelial dysfunction and abnormalities in thrombosis/fibrinolysis system, possibly through increased oxidative stress. In this study we investigated the effect of combined antioxidant treatment with vitamins C and E on endothelial function and plasma levels of plasminogen activator inhibitor (PAI-1), von Willebrand factor (vWF), tissue plasminogen activator (tPA) and factor VII (fVII), in smokers. Forty-one healthy smokers were randomly divided into 4 groups receiving vitamin C 2g/day (group A), vitamin C 2g/day plus vitamin E 400 IU/day (group B), vitamin C 2g/day plus vitamin E 800 IU/day (group C) or no antioxidants (controls, group D), for 4 weeks. Forearm blood flow was measured using venous occlusion strain-gauge plethysmography. Forearm vasodilatory response to reactive hyperemia (RH%) or to sublingual nitroglycerin administration (NTG%) were considered as indexes of endothelium dependent or independent dilation respectively. After treatment, RH% was increased only in groups B (p <0.05) and C (p <0.001) but not in groups A and D. Plasma levels of PAI-1 and vWF were decreased only in group C (p <0.05 for both), while PAI-1/tPA ratio was significantly decreased in both groups B and C (p <0.05 for both). NTG% and plasma levels of tPA and fVII remained invariable in all groups. In conclusion, combined administration of vitamin C and vitamin E at high dosages, improved endothelial function and decreased plasma levels of PAI-1, vWF and PAI-1/tPA ratio in chronic smokers.

Topics: Adult; Antioxidants; Ascorbic Acid; Blood Coagulation Factors; Blood Flow Velocity; Drug Therapy, Combination; Endothelium, Vascular; Female; Fibrinolysis; Hemostasis; Humans; Male; Smoking; Thrombosis; Vitamin E

To examine the effect of vitamin C on forearm vasodilatory response to reactive hyperemia and on plasma level of plasminogen activator inhibitor 1 (PAI-1), von Willebrand factor (vWF), tissue plasminogen activator (tPA), antithrombin III (ATIII), proteins C and S, and factors V (fV) and VII (fVII) in patients with both type 2 diabetes and CAD.. A total of 39 patients with type 2 diabetes and CAD were divided into two groups and received vitamin C (2 g/day) or no antioxidant for 4 weeks. Forearm blood flow was determined using venous occlusion gauge-strain plethysmography at baseline and after treatment. Forearm vasodilatory response to reactive hyperemia (RH%) or nitrate (NTG%) was defined as the percent change of flow from baseline to the maximum flow during reactive hyperemia or after administration of nitrate, respectively. Biochemical markers were determined by enzyme-linked immunosorbent assay (ELISA) or other standard methods.. RH% was significantly increased after treatment with vitamin C (from 62.4 +/- 7.2 to 83.1 +/- 9.3%, P = 0.024) but remained unaffected in the control group. Vitamin C decreased plasma levels of fV (from 143 +/- 5.4 to 123 +/- 6.03%, P = 0.038), vWF (from 133.5 +/- 14.5 to 109.5 +/- 11.4%, P = 0.016), and tPA (from 12.3 +/- 0.99 to 8.40 +/- 0.60 ng/ml, P = 0.001), whereas these levels remained unaffected in the control group. The changes in RH%, vWF, and tPA were significantly greater (P = 0.028, 0.036, and 0.007, respectively) in the vitamin C-treated group than in the control group. Levels of ATIII, proteins S and C, fVII, and PAI-1 remained unchanged in all groups.. Short-term treatment with high doses of vitamin C improved RH% and decreased plasma levels of tPA and vWF in patients with type 2 diabetes and CAD.

Topics: Administration, Oral; Aged; Antioxidants; Antithrombin III; Ascorbic Acid; Coronary Artery Disease; Diabetes Mellitus, Type 2; Factor V; Factor VII; Female; Fibrinolysis; Forearm; Humans; Hyperemia; Male; Middle Aged; Plasminogen Activator Inhibitor 1; Protein C; Protein S; Regional Blood Flow; Thrombosis; Tissue Plasminogen Activator; Vasodilation; von Willebrand Factor

Nutritional antioxidants support prostacyclin synthesis by preventing lipid hydroperoxide-mediated inhibition of prostacyclin synthetase. Recent preliminary clinical studies indicate that supplementary antioxidants exert antithrombotic effects in vivo that are most likely attributable to enhanced prostacyclin production. Optimal antioxidant nutrition may thus have preventive and therapeutic value for disorders in which inappropriate platelet aggregation plays an etiologic role, including MI, stroke, atherogenesis, pre-eclampsia, and the vascular complications of diabetes. In light of evidence that platelet aggregation encourages the implantation of hematogenous tumor metastases, supplemental antioxidants should also impede tumor dissemination--an effect which will be complemented by the immunostimulant actions of these nutrients. By exerting anticarcinogenic, immunostimulant and anti-metastatic effects, nutritional antioxidants should act to inhibit neoplasia at each stage of its development.

Topics: Adjuvants, Immunologic; Animals; Antineoplastic Agents; Antioxidants; Ascorbic Acid; Clinical Trials as Topic; Diet; Epoprostenol; Humans; Lipid Peroxides; Neoplasm Metastasis; Neoplasms; Neoplastic Cells, Circulating; Platelet Aggregation; Selenium; Thrombosis; Vitamin E

Topics: Aged; Ascorbic Acid; Cardiovascular Diseases; Clinical Trials as Topic; Female; Humans; Male; Placebos; Thrombosis

To investigate the effect of ascorbic acid (AA) on hemostatic function during living donor liver transplantation (LDLT).. Blood samples from 21 LDLT recipients were taken within 30 minutes after induction and at 120 minutes after reperfusion. Rotational thromboelastography (TEG) and western blot analysis were used to analyze for fibrinolysis and functional changes in c-Cbl and Cbl-b, respectively. TEG test samples were prepared as one of three groups: C group (0.36 mL of blood), N group (0.324 mL of blood + 0.036 mL of 0.9% normal saline), and A group (0.324 mL of blood + 0.036 mL of 200 µmol/L-AA dissolved in 0.9% normal saline).. AA decreased fibrinolysis and increased clot rigidity at baseline and 120 minutes after reperfusion. Cbl-b expression was significantly increased at baseline and 120 minutes after reperfusion in the A group compared with the C and N groups. However, c-Cbl phosphorylation was most significantly decreased in the A group at baseline and 120 minutes after reperfusion.. AA can significantly decrease fibrinolysis and improve clot rigidity in LT recipients during LDLT, and functional changes in Cbl-b and c-Cbl might represent the underlying mechanism. AA may be considered for use during LDLT to decrease hyperfibrinolysis.

Topics: Antioxidants; Ascorbic Acid; Blood Platelets; Female; Gene Expression Regulation; Humans; Liver Transplantation; Living Donors; Male; Middle Aged; Oncogene Protein v-cbl; Phosphorylation; Prospective Studies; Proto-Oncogene Proteins c-cbl; Thrombosis

Potential risk of high-dose vitamin C consumption is often ignored. Recently, gram-dose vitamin C is being intravenously injected for the treatment of cancer, which can expose circulating blood cells to extremely high concentrations of vitamin C. As well as platelets, red blood cells (RBCs) can actively participate in thrombosis through procoagulant activation. Here, we examined the procoagulant and prothrombotic risks associated with the intravenous injection of gram-dose vitamin C. Vitamin C (0.5-5 mM) increased procoagulant activity of freshly isolated human RBCs via the externalization of phosphatidylserine (PS) to outer cellular membrane and the formation of PS-bearing microvesicles. PS exposure was induced by the dysregulation of key enzymes for the maintenance of membrane phospholipid asymmetry, which was from vitamin C-induced oxidative stress, and resultant disruption of calcium and thiol homeostasis. Indeed, the intravenous injection of vitamin C (0.5-1.0 g/kg) in rats in vivo significantly increased thrombosis. Notably, the prothrombotic effects of vitamin C were more prominent in RBCs isolated from cancer patients, who are at increased risks of thrombotic events. Vitamin C-induced procoagulant and prothrombotic activation of RBCs, and increased thrombosis in vivo. RBCs from cancer patients exhibited increased sensitivity to the prothrombotic effects of vitamin C, reflecting that intravenous gram-dose vitamin C therapy needs to be carefully revisited.

Topics: Adenosine Triphosphate; Animals; Ascorbic Acid; Blood Coagulation; Calcium; Erythrocytes; Flow Cytometry; Glutathione; Hemolysis; Humans; Injections, Intravenous; Leukemia; Male; Microscopy, Electron, Scanning; Neoplasms; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Thrombosis; Vitamins

Antiproliferative drugs such as paclitaxel and sirolimus are delivered from stents to inhibit the growth of smooth muscle cells (SMCs) for preventing neointimal hyperplasia. However, these drugs delay the growth of endothelial cells (ECs) as well and cause late stent thrombosis. We recently demonstrated the use of Vitamin-C (l-ascorbic acid, l-AA) over paclitaxel and sirolimus for inhibiting SMCs growth and promoting EC growth simultaneously. In this study, we have investigated the delivery of l-AA from CoCr alloy surfaces for potential use in stents. A polymer-free phosphoric acid (PA) platform and a polymer-based poly(lactic-co-glycolic acid) (PLGA) platform were used for coating l-AA onto CoCr surfaces. For the PA platform, FTIR confirmed that the PA was coated on CoCr, while the AFM showed that the PA coating on the CoCr surface was homogeneous. The successful deposition of l-AA on PA-coated CoCr was also confirmed by FTIR. The uniform distribution of l-AA crystals on PA-coated CoCr was shown by SEM, optical profilometer, and AFM. The drug release studies showed that l-AA (276 μg/cm(2)) was burst released from the PA platform by 1 h. For the PLGA platform, SEM showed that the l-AA incorporated polymer films were smoothly and uniformly coated on CoCr. FTIR showed that l-AA was incorporated into the bulk of the PLGA film. DSC showed that the l-AA was present in an amorphous form and formed an intermolecular bonding interaction with PLGA. The drug release studies showed that l-AA was sustained released from the PLGA coated CoCr for up to 24 h. The SEM, FTIR, and DSC characterizations of samples collected post drug release shed light on the mechanism of l-AA release from PLGA coated CoCr. Thus, this study demonstrated the delivery of l-AA from biomaterial surfaces for potential applications in stents and other implantable medical devices.

Topics: Alloys; Ascorbic Acid; Biocompatible Materials; Calorimetry, Differential Scanning; Cardiovascular Diseases; Chromium Alloys; Drug Carriers; Drug-Eluting Stents; Humans; Lactic Acid; Materials Testing; Microscopy, Atomic Force; Microscopy, Electron, Scanning; Phosphoric Acids; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Polymers; Prosthesis Design; Prosthesis Failure; Spectroscopy, Fourier Transform Infrared; Thrombosis; Time Factors

Increased vascular contractility plays a fundamental role in cerebral vasospasm in subarachnoid haemorrhage (SAH). We investigated the role of thrombin and its receptor, proteinase-activated receptor 1 (PAR1), and other G protein-coupled receptors in the increased contractility, and examined the preventive effects of the thrombin inhibitor, argatroban, and anti-oxidative agents, vitamin C and tempol.. A rabbit model of SAH was utilized. Contractile responses of the isolated basilar artery and the level of oxidative stress of brain tissues were evaluated.. Contractile responses to thrombin and PAR1-activating peptide (PAR1-AP) were enhanced and prolonged after SAH. The thrombin-induced contraction persisted even after terminating thrombin stimulation. When sequentially stimulated with PAR1-AP, the second response was maintained in SAH, while it was substantially attenuated in the control. Only a combination of argatroban with vitamin C or tempol prevented both the enhancement and prolongation of the contractile response to PAR1-AP and restored the reversibility of the thrombin-induced contraction. The responses to angiotensin II, vasopressin and PGF(2α) were enhanced and prolonged after SAH to varying degrees, and responded differently to the treatment. The response to vasopressin exhibited a similar phenomenon to that seen with PAR1-AP. Oxidative stress was increased in SAH, and normalized by the treatment with argatroban, vitamin C or their combination.. Increased vascular reactivity to agonists in SAH was attributable to the enhancement and prolongation of the contractile response. A combination of argatroban and anti-oxidative agents was required to prevent both the enhancement and prolongation of the contractile response.

Topics: Animals; Antioxidants; Arginine; Ascorbic Acid; Drug Therapy, Combination; Male; Pipecolic Acids; Rabbits; Receptor, PAR-1; Signal Transduction; Subarachnoid Hemorrhage; Sulfonamides; Thiobarbituric Acid Reactive Substances; Thrombin; Thrombosis; Vasoconstriction

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired stem-cell disorder associated with intravascular hemolysis and thrombosis. Hemolysis is caused by the hypersensitivity of PNH-red blood cells (RBC) to complement-mediated lysis due to deficiency in the surface glycosyl phosphatidylinositol-anchored antigens, CD55 and CD59. Thrombosis may be related to the platelet tendency to undergo hyperactivation. We previously suggested that hemolysis and thrombosis in other hemolytic anemias are related to oxidative stress. In the present study, we assessed the oxidative status of blood cells in PNH and tested the potential protective effects of antioxidants.. Blood samples were obtained from 11 PNH patients and 11 normal control donors. Flow cytometry was used to measure oxidative stress markers in conjunction with the PNH immunophenotype.. Results indicated that abnormal, CD55/CD59-negative, RBC, neutrophils, and platelets are under oxidative stress. Their intracellular reactive oxygen species, membrane lipid peroxides, and external phosphatidylserine were higher and their reduced glutathione was lower than CD55/CD59-positive cells of the same patient or cells of normal controls. PNH-RBC were hypersensitive to an oxidative insult (e.g., hydrogen peroxide) and their oxidative status increased following interaction with complement, prior to hemolysis. Antioxidants reduced this hemolysis as well as activation of PNH platelets.. We propose that oxidative stress mediates the symptoms of PNH and suggest that antioxidants might be considered as a therapeutic modality.

Topics: Acetylcysteine; Anemia; Antioxidants; Ascorbic Acid; Biomarkers; Blood Platelets; Erythrocytes; Female; Flow Cytometry; Hemoglobinuria, Paroxysmal; Humans; Hydrogen Peroxide; Male; Neutrophils; Oxidants; Oxidative Stress; Reference Values; Thrombosis; Tocopherols

To examine the modulation of arterial thrombosis by vitamins C and E, Sprague-Dawley rats were fed nonpurified diet, or diet mixed with vitamin C [100 mg/(kg body weight.d)], vitamin E [100 mg/(kg.d)] or both vitamins C and E [each 100 mg/(kg.d)], for a period of 9-19 d (mean 15 d). An occlusive aortic thrombus was created by application of a Whatman filter soaked in 1 mol/L FeCl3. Both vitamins C and E and their combination decreased platelet aggregation and delayed time to occlusive thrombus formation (P < 0.05 vs. control). Vitamins C and E decreased arterial superoxide generation (P < 0.05 vs. control). Interestingly, vitamin E also increased endogenous superoxide dismutase activity (SOD) and protein expression in aortic tissues (P < 0.05 vs. control). The combination of vitamins C and E was not superior to each vitamin alone with regard to effect on time to thrombus formation, but it was more potent with regard to platelet inhibition. The increase in endogenous antioxidant activity by vitamin E is an intriguing observation. This study shows that the antioxidant vitamins C and E have important effects on platelet aggregation, SOD activity, superoxide generation and thrombus formation.

Topics: Animals; Arteries; Ascorbic Acid; Drug Combinations; Male; Platelet Aggregation; Platelet Aggregation Inhibitors; Rats; Rats, Sprague-Dawley; Superoxide Dismutase; Superoxides; Thrombosis; Time Factors; Vitamin E

To explore the hypothesis that a relationship exists between free radical activity and abnormalities in hemostasis in NIDDM.. The use of the total radical-trapping antioxidant parameter (TRAP) has very recently been proposed to explore the antioxidant property of a plasma and their mutual cooperation. In the present study, TRAP, vitamin E, vitamin C, vitamin A, uric acid, protein-bound SH (thiol) groups, fibrinogen, prothrombin fragments F1 + 2, and D-dimer have been evaluated in 46 NIDDM patients and 47 healthy matched control subjects.. In NIDDM patients, TRAP, vitamin A, SH groups, and uric acid were significantly reduced, whereas the level of vitamin E was significantly increased. Vitamin C was similar in the two groups. Fibrinogen, prothrombin fragment 1 + 2, and D-dimer were increased in diabetic patients. TRAP, but no single other antioxidant, had a strong inverse association with fibrinogen, prothrombin fragment 1 + 2, and D-dimer.. These findings are consistent with the hypothesis that oxidative stress may condition coagulation activation in diabetics. However, the data suggest that it is the total antioxidant capacity rather than any single plasma antioxidant that is the most relevant parameter.

Topics: Antioxidants; Ascorbic Acid; Case-Control Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Fibrin Fibrinogen Degradation Products; Fibrinogen; Hemostasis; Humans; Male; Middle Aged; Peptide Fragments; Predictive Value of Tests; Protein Precursors; Prothrombin; Reference Values; Regression Analysis; Risk Factors; Thrombosis; Uric Acid; Vitamin A; Vitamin E

Prior work in our laboratory showed that the perivascular application of deferoxamine (an antioxidant and iron-chelating agent) inhibited delayed arterial narrowing after chronic blood exposure in a rat femoral artery model of vasospasm. To determine which of these mechanisms was operant in vasospasm, we compared deferoxamine with two agents (ascorbic acid and U74389F) that have antioxidant but not iron-chelating capacity. For the systemic application of drugs in 23 rats, whole blood encased in a silastic cuff was applied to the right femoral artery of each rat; whole-blood serum (lacking erythrocytes) was similarly applied to the left femoral artery. Deferoxamine (30 mg/kg/d), ascorbic acid (1000 mg/kg/d), U74389F (30 mg/kg/d), or pH-matched control vehicle was administered three times daily by intraperitoneal injection for 7 days. After exposure to whole blood, arteries treated with intraperitoneal vehicle showed an 85% reduction in the lumen, compared with vessels exposed to erythrocyte-free serum (P < 0.001). Intraperitoneal ascorbic acid and U74389F produced moderate amelioration in arterial narrowing (53 and 61% decrease, respectively, in the lumen versus controls; P < 0.05 versus vehicle); deferoxamine had no significant effect when administered intraperitoneally. To test the efficacy of these agents by the perivascular application of drugs, whole blood was applied to both femoral arteries in each of 25 rats. Solutions of deferoxamine (10 mg/ml), ascorbic acid (50 or 100 mg/ml), or U74389F (15 or 30 mg/ml) were directly applied to the perivascular thrombus surrounding the femoral arteries, compared with vehicle applied to contralateral vessels. The perivascular application of 50 mg of ascorbic acid (36% reduction, P < 0.05), 100 mg of ascorbic acid (31% reduction, P < 0.01), or 10 mg of deferoxamine (41% reduction, P < 0.05) significantly inhibited arterial narrowing, compared with vehicle. The application of U74389F at a dose of 15 or 30 mg directly into the perivascular thrombus produced nonsignificant reduction in arterial narrowing. These data suggest that mechanisms other than direct iron toxicity, such as generation of cytotoxic free radicals, may play an important role in cerebral vasospasm. In addition, the route of administration and concentration of drugs in the perivascular region adjacent to the thrombus may be critical to their efficacy.

Topics: Animals; Antioxidants; Ascorbic Acid; Deferoxamine; Dose-Response Relationship, Drug; Femoral Artery; Free Radicals; Iron; Iron Chelating Agents; Ischemic Attack, Transient; Male; Pregnatrienes; Rats; Rats, Sprague-Dawley; Thrombosis; Vascular Resistance

The role of free radicals in rat thrombosis has been demonstrated by studying its scavenging enzyme system. Changes in the bio-antioxidants (GSH-redox cycle, total thiol groups, vitamins E and C) that also offer protection against the free radicals, have, however, not been studied so far. This investigation was undertaken to understand the involvement of these antioxidants during thrombosis. The tissues investigated following thrombosis were blood, platelets, polymorphonuclear leukocytes (PMNLs), heart, and lung. Glutathione (GSH) content in the platelets was observed to be depleted. However, oxidized glutathione (GSSG) contents in the platelets, PMNLs, and blood remain unaltered. In addition, in the whole blood GSH levels were increased significantly, whereas there was no change in the GSSG level. Activity of glutathione reductase (GR) was decreased significantly in platelets and lungs with an increase in the total thiol groups in the lung homogenate. Activity of Glutathione peroxidase (Gpx) remained unaltered in all the tissues studied. In addition, 24% and 15% decrease in the alpha-tocopherol concentration was observed in thrombocytes and PMNLs, respectively, with no change in the ascorbate levels in these cells. Results of this investigation suggest alterations in the GSH-redox cycle in blood, platelets, and lung after thrombosis in the rat.

Topics: Animals; Antioxidants; Ascorbic Acid; Blood Platelets; Collagen; Epinephrine; Glutathione; Glutathione Disulfide; Glutathione Peroxidase; Glutathione Reductase; Lung; Myocardium; Neutrophils; Rats; Rats, Sprague-Dawley; Reference Values; Thrombosis; Vitamin E

We have studied the influence of ascorbate on extracellular matrix formation in cultured human endothelial cells, smooth muscle cells and fibroblasts and measured the influence of the changed composition of their isolated extracellular matrices on their affinity for platelets. When endothelial cells were grown for a week in the presence of ascorbate, no influence on proline incorporation in their extracellular matrix was found. In accordance, no influence on platelet adhesion or aggregate formation on these matrices was detected. When smooth muscle cells were cultured in the presence of ascorbate, a strong increase in the amount of collagen types I and III in the extracellular matrix was found. When these matrices were perfused with whole blood, a significant enhanced increase in aggregate formation was observed. No influence was seen on the total coverage of the matrix with platelets. When fibroblasts were grown in the presence of ascorbate, no significant increase in proline incorporation in their matrix was measured. However, an increased adhesion of platelets was seen to the matrices at lower shear rates. We conclude that ascorbate feeding has a significant effect on endogenous deposited matrices of smooth muscle cells and fibroblasts, and that the changed composition had profound effects on platelet interaction with these matrices.

Topics: Ascorbic Acid; Cells, Cultured; Collagen; Endothelium, Vascular; Extracellular Matrix; Fibroblasts; Humans; Muscle, Smooth; Platelet Adhesiveness; Thrombosis

High but well-tolerated doses of the nutritional antioxidants selenium and vitamins E and C have significant immunostimulant, anti-inflammatory, and anti-carcinogenic effects which are well documented in the existing biomedical literature. In addition, these antioxidants help to protect the structural integrity of ischemic or hypoxic tissues, and may have useful anti-thrombotic actions as well. Supplementation with high-dose nutritional antioxidants may eventually gain a broad role in the prevention, treatment, or palliation of cancer, cardiovascular disease, infection, inflammatory disorders, and certain diabetic complications.

Topics: Adjuvants, Immunologic; Animals; Anti-Inflammatory Agents; Antioxidants; Arthritis; Ascorbic Acid; Cardiovascular Diseases; Diabetes Mellitus; Free Radicals; Humans; Hypoxia; Ischemia; Mice; Neoplasms; Rabbits; Rats; Selenium; Superoxides; Thrombosis; Vitamin E

Topics: Aged; Arteriosclerosis; Ascorbic Acid; Ascorbic Acid Deficiency; Cholesterol; Coronary Disease; Female; Humans; Male; Middle Aged; Thrombosis

Topics: Adult; Aged; Anus Diseases; Ascorbic Acid; Coumarins; Female; Flavonoids; Hemorrhoids; Humans; Male; Middle Aged; Plant Extracts; Rectal Diseases; Thrombosis

Topics: Adenosine Triphosphate; Arteriosclerosis; Ascorbic Acid; Blood Coagulation Disorders; Fibrinolytic Agents; Heparin; Humans; Inositol; Nicotinic Acids; Thrombosis

Topics: Ascorbic Acid; Head; Humans; Intracranial Embolism; Intracranial Embolism and Thrombosis; Skull; Thrombosis; Vitamins

Topics: Ascorbic Acid; Coumarins; Female; Flavonoids; Genitalia; Genitalia, Female; Gynecology; Humans; Obstetrics; Postpartum Period; Thrombosis; Venous Thrombosis; Vitamin E; Vitamins

Topics: Anticoagulants; Ascorbic Acid; Female; Genital Diseases, Female; Gynecology; Humans; Obstetrics; Pregnancy; Thrombophlebitis; Thrombosis; Venous Thrombosis; Vitamin E