thromboxane-b2 and Diabetic-Retinopathy

Ticlopidine, a thienopyridine that prevents the progression of diabetic retinopathy in humans, was recently shown to increase nitric oxide (NO) production in human neutrophils. The thienopyridine clopidogrel has been found to be clinically useful in the secondary prevention of thrombotic events. The aim of the present study was to evaluate the effect of clopidogrel on ischemic retinopathy in streptozotocin-diabetic rats and its influence on prostanoids and NO production. We compared nondiabetic rats and rats after 3 months of diabetes that were given three doses (1, 10 or 20 mg/kg per day p.o.) of ticlopidine or clopidogrel from the first day of diabetes. The variables recorded after 3 months of diabetes were platelet aggregation, thromboxane B(2) (TxB(2)) production, 6-keto-prostaglandin F(1)(alpha) (stable metabolite of prostacyclin), aortic NO, plasma nitrites/nitrates, and the percentage of the retinal surface occupied by horseradish peroxidase (HRP)-permeable vessels. In diabetic rats, platelet aggregation and thromboxane concentration were increased, and prostacyclin, NO and area occupied by HRP-permeable vessels were decreased. Ticlopidine and clopidogrel reduced the maximum extent of platelet aggregation in a dose-dependent manner: maximal inhibition with respect to untreated diabetic rats was 48.6% with ticlopidine and 66.6% with clopidogrel. Ticlopidine reduced thromboxane B(2) only at a dose of 20 mg/kg per day p.o. (47.4% inhibition) and clopidogrel at doses of 10 mg/kg per day (51% inhibition) or 20 mg/kg per day (51.7% inhibition). Aortic prostacyclin production did not change after treatment with either thienopyridine. Treatment with ticlopidine reduced the inhibition of NO production in untreated rats (89.6% inhibition) to 0.9%, and clopidogrel reduced inhibition to 30%. Treatment with ticlopidine or clopidogrel reduced the retinal nonperfused area from 86.8% inhibition in untreated rats to 45.6% and 25.3%, respectively. In conclusion, the early administration of thienopyridines in streptozotocin-diabetic rats partly prevented the appearance of diabetic retinal ischemia.

Topics: 6-Ketoprostaglandin F1 alpha; Administration, Oral; Animals; Clopidogrel; Diabetes Mellitus, Experimental; Diabetic Retinopathy; Dose-Response Relationship, Drug; Male; Nitrates; Nitric Oxide; Nitrites; Platelet Aggregation Inhibitors; Rats; Rats, Wistar; Retinal Vessels; Thromboxane B2; Ticlopidine

Combined thromboxane synthase inhibitors and thromboxane receptors antagonists have been shown to have a beneficial effect on different models of thrombosis in vivo. We studied the action of one of these compounds (DT-TX 30) compared with dazoxiben (a thromboxane synthase inhibitor) on retinal vascularity in streptozotocin-diabetic rats. Ten nondiabetic animals were treated with isotonic saline, 30 (10 animals per group) were given 0.4, 4, and 8 mg kg(-1) per day of DT-TX 30 (p.o.) and 30 (10 animals per group) were given 10, 50, and 100 mg kg(-1) per day of dazoxiben (p.o.) over a 90-day study period. DT-TX 30 caused a dose-dependent decrease of platelet aggregation and thromboxane B2 synthesis. There was an increase of 9, 65, and 166% in the synthesis of prostacyclin after treatment with 0.4, 4, and 8 mg kg(-1) per day, respectively. Retinal vascularity increased in 51, 72, and 182% of animals in response to the three doses used. Synthesis of prostacyclin and the degree of retinal vascularity showed a linear correlation (r2=0.6528,p<0.00001). Dazoxiben, at doses that inhibited thromboxane synthesis as much as DT-TX 30, increased prostacyclin production and retinal vascularity with less potency than DT-TX 30. In conclusion, the antagonism of thromboxane receptors may be an important additional effect to the inhibition of thromboxane synthase in the prevention of ischemic retinal lesions in experimental diabetes.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Blood Glucose; Chlorobenzenes; Collagen; Diabetes Mellitus, Experimental; Diabetic Retinopathy; Enzyme Inhibitors; Imidazoles; Male; Platelet Aggregation; Pyridines; Rats; Rats, Wistar; Receptors, Thromboxane; Retinal Vessels; Thromboxane B2; Thromboxane-A Synthase

Platelet hyperactivity accompanied by an increased synthesis of thromboxane and/or a decreased prostacyclin production are important factors in ischemic diabetic retinopathy. We studied the effect of camonagrel and dazoxiben, two thromboxane synthase inhibitors, on retinal vascularization in a model of streptozotocin-induced diabetes in rats. Ten nondiabetic rats, 10 diabetic animals treated with saline (i.e., not treated), and 60 diabetic animals treated with dazoxiben or camonagrel (10, 50 or 100 mg kg(-1) day(-1) p.o.) were studied. All treatments lasted for 90 days. Dazoxiben and camonagrel produced a dose-dependent reduction in platelet aggregation and thromboxane synthesis. Dazoxiben increased prostacylin synthesis by 78% at 100 mg kg(-1) day(-1), and camonagrel by 154%. Dazoxiben increased retinal vascularity by 74%, and by 183% after camonagrel treatment. Prostacyclin synthesis showed a direct linear correlation with the degree of retinal vascularization (r2=0.6733, P < 0.00001). We conclude that an increased prostacyclin synthesis may have a greater influence than the inhibition of thromboxane synthesis in preventing ischemic diabetic retinopathy in experimental diabetes. Camonagrel may be an alternative treatment in the prevention of these lesions.

Topics: Animals; Blood Cell Count; Blood Glucose; Diabetes Mellitus, Experimental; Diabetic Retinopathy; Enzyme Inhibitors; Fibrinolysis; Imidazoles; Indans; Male; Platelet Aggregation; Platelet Aggregation Inhibitors; Rats; Rats, Wistar; Retinal Neovascularization; Streptozocin; Thromboxane B2; Thromboxane-A Synthase

Specific antagonists of platelet-activating factor (PAF) receptors inhibit platelet aggregation and thromboxane synthesis. These two processes have been implicated in the course of diabetic retinopathy. We assessed the effect of a specific PAF receptor antagonist, WEB 2086-BS (3-(4-(2-chlorophenyl)-9-methyl-6H-thieno(3,2-f) (1,2,4 triazolo-(4,3-a(1,4)-diazepine-2-yl)-1-(4-morpholinyl)-1-propanone) on retinal vascularity in a model of experimental streptozocin-induced diabetes in rats. Rats were divided into five experimental groups (10 animals/group): group I, non-diabetic group II, untreated diabetic group III, diabetic given 1 mg/kg per day of WEB 2086-BS (p.o.) group IV, diabetic given 5 mg/kg per day (p.o.) and group V, diabetic given 10 mg/kg per day (p.o.). After 3-month treatment, platelet aggregometry, platelet synthesis of thromboxane B2, aortic production of 6-keto-prostaglandin F1alpha, platelet and vascular lipid peroxidation, and percentage of the retinal area occupied by horseradish peroxidase-labeled vessels were measured. Untreated diabetic rats showed an increase in platelet reactivity, reduced 6-keto-prostaglandin F1alpha production, increased thromboxane B2 and lipid peroxides, and a decrease in the percentage of retinal area occupied by horseradish peroxidase-labeled vessels. WEB 2086-BS produced a decrease in platelet aggregation induced by collagen in whole blood, in thromboxane B2 synthesis and lipid peroxide production, and an increase in the percentage of retinal area occupied by horseradish peroxidase-labeled vessels (13.9+/-1.1% in group II and 9.9+/-0.8% in group V). There was a statistically significant linear correlation (Y= -0.72 + 137X, r2 = 0.7247, P < 0.0007) between thromboxane B2 values and the percentages of retinal area occupied by horseradish peroxidase-labeled vessels in the groups of animals treated with WEB 2086-BS.

Topics: Analysis of Variance; Animals; Azepines; Blood Glucose; Blood Platelets; Diabetes Mellitus, Experimental; Diabetic Retinopathy; Dose-Response Relationship, Drug; Epoprostenol; Lipid Peroxidation; Male; Neovascularization, Pathologic; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Membrane Glycoproteins; Rats; Rats, Wistar; Receptors, Cell Surface; Receptors, G-Protein-Coupled; Retina; Thromboxane B2; Triazoles

Omega-3 fatty acids exert several important biological effects on factors that may predispose to diabetic retinopathy. Potential pathogenetic mechanisms include platelet dysfunction, altered eicosanoid production, increased blood viscosity in association with impaired cell deformability and pathologic leucocyte/endothelium interaction. Therefore, we tested whether a 6-month administration of fish oil (750 mg Maxepa, 5 times per week), containing 14% eicosapentaenoic acid (EPA) and 10% docosahexaenic acid, could inhibit the development of experimental retinopathy of the streptozotocin-diabetic rat. The efficiency of fish oil supplementation was evaluated by measuring EPA concentrations in total, plasma and membrane fatty acids and by measuring the generation of lipid mediators (leukotrienes and thromboxanes). Retinal digest preparations were quantitatively analysed for pericyte loss, and the formation of acellular capillaries. Omega-3 fatty acid administration to diabetic rats resulted in a twofold increase of EPA 20:5 in total fatty acids, and a reduction of the thromboxane ratio from 600 (untreated diabetic rats) to 50 (treated diabetic rats). Despite these biochemical changes, diabetes-associated pericyte loss remained unaffected and the formation of acellular, occluded capillaries was increased by 75% in the fish oil treated diabetic group (115.1 +/- 26.8; untreated diabetic 65.2 +/- 15.0 acellular capillary segments/mm2 of retinal area). We conclude from this study that dietary fish oil supplementation may be harmful for the diabetic microvasculature in the retina.

Topics: Animals; Blood Glucose; Blood Viscosity; Capillaries; Diabetes Mellitus, Experimental; Diabetic Retinopathy; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids; Fatty Acids, Omega-3; Fish Oils; Glycated Hemoglobin; Glycation End Products, Advanced; Leukotrienes; Male; Membrane Lipids; Neutrophils; Rats; Rats, Inbred Lew; Retina; Retinal Vessels; Thromboxane B2

To investigate the possible relevance of free radicals and prostanoids to the mode of initiation and/or evolution of microangiopathy in diabetes mellitus, we measured serum lipid peroxides (LPO), an accepted index of intravascular free radicals, and plasma 11-dehydrothromboxane B2 (11-dehydro-TXB2), a stable metabolite of vasoactive thromboxane A2 released from platelets, in 95 patients with normolipidemic type 2 (non-insulin-dependent) diabetes mellitus at different stages of the disease. In general, either LPO or 11-dehydro-TXB2 was significantly greater in the patients, as a group, than in the matched controls (3.82 vs. 2.65 nmol/ml, P < 0.01 for LPO; and 17.3 vs. 5.8 pg/ml, P < 0.01 for 11-dehydro-TXB2). In patients, both LPO and 11-dehydro-TXB2 increased according to the severity of their diabetic retinopathy. A highly significant positive correlation existed between the LPO values and 11-dehydro-TXB2 in the patients (r = 0.64, P < 0.0001), while there was no such relationship in the controls (r = 0.18, P = NS). No difference in serum levels of apolipoproteins A-I, A-II, B, C-II, C-III, or E was observed between the patients and controls. Short-term glycemic control (25 cal/kg of standardized body weight/day, for 8 weeks) resulted in a small but significant reduction in LPO (4.2 vs. 4.6 nmol/ml, control; P < 0.05) without alteration in 11-dehydro-TXB2. There was a tendency towards deterioration in LPO according to the improvement in glycemic control. These results appear consistent with the view that, in addition to LPO, the release of TXA2 from activated platelet in the human circulation could be an important factor for the initiation and/or evolution of microangiopathy in diabetic patients even when they are not apparently hyperlipidemic. Further, the results of the present study emphasize the notion that more tight control of serum lipids is worthy of serious consideration in preventing the advance of diabetic microangiopathy.

Topics: Aged; Apolipoproteins; Biomarkers; Blood Glucose; Cholesterol; Cholesterol, HDL; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Nephropathies; Diabetic Retinopathy; Female; Free Radicals; Glycated Hemoglobin; Humans; Lipid Peroxidation; Lipid Peroxides; Male; Middle Aged; Reference Values; Thromboxane B2; Triglycerides

Topics: 6-Ketoprostaglandin F1 alpha; Diabetes Mellitus; Diabetic Retinopathy; Humans; Thromboxane B2

Increased free radical activity may contribute to thrombosis via effects on platelet aggregation and the prostanoid balance. To investigate this further we studied 15 Type 1 diabetic patients with retinopathy, matched with uncomplicated Type 1 patients for age, duration of diabetes and HbA1, together with matched healthy non-diabetic control subjects. The oxidative effects of free radicals as total diene conjugates and lipid peroxides were measured, together with redox status extracellularly as plasma albumin-thiols and intracellularly as erythrocyte superoxide dismutase activity. Platelet count, aggregation of platelets in whole blood to collagen, thromboxane B2, and prostacyclin stimulating factor (PGI2SF) were also assessed. Free radicals measured as lipid peroxides were significantly higher (9.6 (8.1-11.6) mumol l-1 (median and interquartile range) in diabetic patients with retinopathy than in control subjects (8.1 (7.4-9.2) mumol l-1; p less than 0.05). There were also significant reductions in redox status both extracellularly as plasma albumin thiols (408 (383-473) vs 490 (456-517) mumol l-1, p less than 0.001) and intracellularly as erythrocyte superoxide dismutase activity (34 (27-41) vs 44 (36-51) g l-1, p less than 0.05) between patients with retinopathy and control subjects. Platelet counts were increased in diabetic patients with retinopathy (p less than 0.05), as was collagen-induced platelet aggregation (p less than 0.01). Prostacyclin stimulating factor was reduced in patients with retinopathy (p less than 0.05) and correlated within the plasma with lipid peroxides (r = -0.53, p less than 0.04) and albumin thiols (r = 0.64, p less than 0.01). The results suggest that diabetic patients, particularly with retinopathy, are under oxidative stress and have an increased thrombotic tendency with increased platelet reactivity and a reduction in prostacyclin stimulating factor.

Topics: Adult; Biological Factors; Blood Glucose; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diabetic Retinopathy; Female; Glycated Hemoglobin; Humans; Lipid Peroxides; Male; Malondialdehyde; Reference Values; Serum Albumin; Sulfhydryl Compounds; Superoxide Dismutase; Thromboxane B2

Recently the beneficial effects of captopril (angiotensin-converting-enzyme inhibitor) on diabetic nephropathy, especially proteinuria, have been reported by some investigators. The mechanism whereby proteinuria is reduced, however, have not been clarified yet. The present study was undertaken to evaluate the effects of captopril on urinary albumin excretion in relation to urinary prostaglandins (PGs) excretion in patients with non-insulin-dependent diabetes mellitus (NIDDM). Captopril (37.5 mg/day) was orally administered to 13 diabetic patients for an eight-week period. A single administration of captopril (12.5 mg) was performed in the same patients. The spot urine samples were collected in the early morning and 2 hr after the single administration of captopril. The albumin index (mg/gram-creatinine) was markedly decreased in eight patients (Group A) within four weeks, but no decrease was found in five patients (Group B). Furthermore, in Group A, by the single administration of captopril urinary excretions of 6-keto-PCF1 alpha (a stable metabolite of PGI2) and PGE2 were significantly (p less than 0.05) increased while urinary TXB2 (a stable metabolite of TXA2) excretion did not change significantly. The urinary 6-keto-PGF1 alpha/TXB2 ratio, which is significantly (p less than 0.05) low in diabetic patients was significantly (p less than 0.01) increased up to the normal value in Group A. In Group B, however, there were no significant changes in urinary PGs excretion. These results suggest that captopril enhances the production of intrarenal vasodilatory PGs such as PGI2 and PGE2, which may be deeply involved in the reduction of intraglomerular capillary pressure and urinary protein excretion in diabetic patients.

Topics: 6-Ketoprostaglandin F1 alpha; Albuminuria; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Diabetic Retinopathy; Female; Humans; Male; Middle Aged; Prostaglandins; Thromboxane B2

Although several investigators have attempted to measure the plasma levels of prostacyclin (PGI2) and thromboxane A2 (TXA2) in diabetes and normal subjects, their results have been controversial. In this study, we measured plasma PGI2 and TXA2 levels in diabetic patients and normal subjects. The plasma PGI2 and TXA2 were determined by RIA as 6-keto-PGF1 alpha and TXB2, respectively. The plasma levels of 6-keto-PGF1 alpha were significantly reduced in diabetics with microangiopathy (52.5 +/- 18.9 pg/ml, mean +/- SE, p less than 0.05) compared with those of normal subjects. Diabetics as a whole also showed lower levels of 6-keto-PGF1 alpha than normal subjects (57.8 +/- 26.1 vs. 70.2 +/- 20.7 pg/ml), though this was not significant statistically. The plasma 6-keto-PGF1 alpha levels did not significantly correlate with either age of the patients or duration of diabetes in diabetics. Interestingly, however, hemoglobin A1c significantly correlated inversely with 6-keto-PGF1 alpha levels in diabetics without microangiopathy (r = -0.60, p less than 0.05). The plasma levels of TXB2 in diabetics were significantly higher than those of normal subjects (155.2 +/- 69.5 vs. 108.0 +/- 30.0 pg/ml, p less than 0.05). These data suggest that an imbalance of circulating PGI2 and TXA2 may contribute to the development of diabetic microangiopathy.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Blood Glucose; Diabetes Mellitus; Diabetic Retinopathy; Epoprostenol; Glycated Hemoglobin; Humans; Middle Aged; Thromboxane A2; Thromboxane B2

Coagulation parameters, platelet aggregation, and thromboxane production as well as metabolic parameters were measured in 31 diabetic patients, 12 without and 19 with clinically manifest late complications, and in 14 healthy control subjects. Spontaneous in vitro aggregation as well as ADP, collagen, and arachidonic acid induced aggregation were higher in both groups of diabetic patients, without an increase in thromboxane B2 production. In diabetic patients with late complications an increase in fibrinogen, fibrinogen cyanogen bromide peptide, factor VIII related antigen, C1-esterase inhibitor, and antithrombin III was observed in comparison to healthy subjects. Fibrinogen, C1-esterase inhibitor, and factor VIII related antigen were already elevated in diabetic patients without clinically manifest late vascular complications. No strict correlations were found between serum glucose, glycosylated hemoglobin, and glycosylated albumin, on the one hand, and coagulation promoting or inhibiting factors, aggregation or thromboxane B2 production, on the other, in either control or diabetic subjects. Also no correlations existed between the coagulation parameters and the aggregation results. In vitro incubation of pooled normal plasma with different glucose concentrations had no influence on the methods by which the coagulation parameters were measured. These data indicate that rather early in the diabetic state many changes take place in different phases of the thrombostatic process, all resulting in an increased hemostatic diathesis.

Topics: Adult; Antithrombin III; Blood Coagulation Tests; Blood Glucose; Complement C1 Inactivator Proteins; Diabetes Mellitus; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; Fibrinogen; Humans; Platelet Aggregation; Thromboxane B2

Platelets from diabetics are known to be more sensitive in vitro to a variety of aggregating agents, to produce more prostaglandin endoperoxides and thromboxane and to bind more 125I-fibrinogen than platelets from normal controls Fibrinogen binding to platelets is a pre-requisite for platelet aggregation. Previous studies suggested a role for prostaglandins and/or thromboxane A2 in the exposure of fibrinogen receptors on platelets. The present study compares fibrinogen receptors on platelets. The present study compares fibrinogen binding to hyperaggregable platelets from diabetic patients and to normal platelets when prostaglandin/thromboxane formation is suppressed by aspirin. It was found that pre-treatment with aspirin reduced collagen or thrombin-induced binding to platelets from non-retinopathic diabetics to the values seen in controls. By contrast, aspirin did not normalize binding to platelets obtained from retinopathic diabetics. The combination of aspirin with apyrase (an ADP scavenger) almost completely inhibited binding and aggregation of platelets from normal controls or non-retinopathic diabetics exposed to collagen or thrombin, whereas it only partially affected binding and aggregation of platelets from retinopathics. By using a monoclonal antibody (B59.2) to the platelet receptor for fibrinogen, we determined that this receptor was quantitatively and qualitatively the same on platelets from normal controls and diabetics. We conclude that increased fibrinogen binding and hyperaggregability of platelets from non-retinopathic diabetics is related to their capacity to form more prostaglandin endoperoxides/thromboxane than normal platelets. In contrast, hyperaggregability and increased binding of platelets from retinopathics appear at least partly related to a mechanism independent of ADP release and thromboxane synthesis.

Topics: Blood Platelets; Diabetes Mellitus, Type 1; Diabetic Retinopathy; Fibrinogen; Humans; Platelet Aggregation; Platelet Membrane Glycoproteins; Receptors, Cell Surface; Thromboxane B2

Basal and two hours after 600 mg acetylsalicylic acid (ASA) bleeding times were measured in 21 type I diabetic patients with retinopathy, 24 type I diabetic patients without retinopathy and 21 normal healthy volunteers. There were no significant differences either in basal or in after ASA bleeding times between these groups, but the percentage increase in bleeding time after ASA was significantly higher than normal in both diabetic groups. No correlation was found between basal--bleeding time and glucose, Hb A1 or lipid profile. TXB2 production by spontaneous blood clotting was drastically reduced by ASA in both diabetic and normal groups. Platelet hyperactivity in diabetes mellitus may be due, at least in part, to a predominance of the proaggregatory effects of TXA2 over the antiaggregatory effects of PGI2.

Topics: Adolescent; Adult; Aspirin; Bleeding Time; Diabetes Mellitus, Type 1; Diabetic Retinopathy; Female; Glycated Hemoglobin; Humans; Lipids; Male; Thromboxane B2

Vitamin E is known to be an inhibitor of platelet prostaglandin production and aggregation. The rate of platelet aggregation induced by adenosine diphosphate was significantly increased in diabetics with proliferative retinopathy, and the enhanced production of thromboxane B2, a stable metabolite of thromboxane A2, was demonstrated in those patients. On the other hand, vitamin E was significantly reduced in platelets obtained from diabetics as compared to age matched control subjects. In addition, it was shown that vitamin E content in platelets examined in diabetic and control subjects inversely correlated with both the rate of platelet aggregation and thromboxane B2 production during aggregation. It is suggested that the reduced vitamin E levels in diabetic platelets can contribute to the mechanisms of the enhanced platelet thromboxane A2 production and aggregation which lead to the development of vascular complications.

Topics: Adenosine Diphosphate; Adult; Blood Platelets; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Female; Humans; Male; Middle Aged; Platelet Aggregation; Thromboxane B2; Vitamin E

Vitamin E is known to be an inhibitor of platelet prostaglandin production and aggregation. The rate of platelet aggregation induced by adenosine diphosphate was significantly increased in diabetics with proliferative retinopathy and the enhanced production of thromboxane B2, a stable metabolite of thromboxane A2, was demonstrated in those patients. On the other hand, vitamin E in platelets was significantly reduced in diabetics compared with age matched controls. In addition, it was shown that vitamin E content in platelets examined in diabetic and control subjects inversely correlated with both the rate of platelet aggregation and thromboxane B2 production during aggregation. It is suggested that the reduced vitamin E levels in diabetic platelets can contribute to the mechanisms of the enhanced platelet thromboxane production and aggregation which relate to the development of vascular complications.

Topics: Blood Platelets; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Humans; Middle Aged; Platelet Aggregation; Thromboxane B2; Vitamin E

Platelet aggregation is known to be increased in diabetes mellitus, and the enhanced thromboxane production has been shown to be one of the causes of such abnormal platelet function. To investigate which step is activated in diabetic prostaglandin metabolism, three specific inhibitors of prostaglandin synthetases were used in this study, which were mepacrine, indomethacin and imidazole. Platelet aggregation induced by collagen was significantly increased accompanying enhanced thromboxane production in diabetics with proliferative retinopathy compared with age matched controls. Platelet aggregation in diabetics with proliferative retinopathy was less inhibited by the addition of each inhibitor compared with controls. However, there was no difference in inhibitory pattern of platelet aggregation among the three inhibitors. In addition, thromboxane production during aggregation in diabetics with proliferative retinopathy was significantly greater than that in controls by the addition of each inhibitor. Inhibitory patterns of thromboxane production did not differ among the addition of three inhibitors. It is concluded that enhanced thromboxane production resulting in enhanced platelet aggregation would be related to diabetic vascular complications. This abnormal prostaglandin production can be due to the activation of general steps in prostaglandin metabolism in diabetic platelets, not of a specific enzyme.

Topics: Adult; Diabetes Mellitus; Diabetic Retinopathy; Female; Humans; Imidazoles; Indomethacin; Male; Middle Aged; Platelet Aggregation; Quinacrine; Thromboxane B2; Thromboxanes