thromboxane-a2 and Albuminuria

A randomised trial of the effects of 15 gm per day of a fish oil supplement (MaxEPA) on blood lipids, haemostatic variables (including platelet function) and albuminuria was undertaken in 41 insulin dependent diabetics. Compared with the control group there was a significant reduction in thromboxane production by platelets stimulated by collagen in vitro in the group who took the fish oil supplement. The extent of platelet aggregation was not altered but the lag phase before aggregation was prolonged. There were also statistically significant increases in plasma LDL cholesterol, fibrinogen and clotting factor X in the group who took the fish oil supplement. No other significant differences were noted.

Topics: Administration, Oral; Adult; Albuminuria; Blood Coagulation Tests; Blood Platelets; Diabetes Mellitus, Type 1; Diet, Diabetic; Docosahexaenoic Acids; Drug Combinations; Eicosapentaenoic Acid; Erythrocyte Membrane; Fatty Acids, Unsaturated; Female; Fish Oils; Hemostasis; Humans; Middle Aged; Platelet Function Tests; Thromboxane A2

Platelet activation is persistently enhanced, and its inhibition by low-dose aspirin is impaired in type 2 diabetes mellitus. We investigated in vivo thromboxane (TX) and prostacyclin (PGI2) biosynthesis and their determinants, as well as aspirin responsiveness, in young adult subjects with type 1 diabetes mellitus (T1DM) without overt cardiovascular disease and stable glycemic control. The biosynthesis of TXA2 was persistently increased in subjects with T1DM versus matched healthy subjects, with females showing higher urinary TX metabolite (TXM) excretion than male subjects with T1DM. Microalbuminuria and urinary 8-iso-PGF2α, an index of in vivo oxidative stress, independently predicted TXM excretion in T1DM. No homeostatic increase in PGI2 biosynthesis was detected. Platelet COX-1 suppression by low-dose aspirin and the kinetics of its recovery after drug withdrawal were similar in patients and control subjects and were unaffected by glucose variability. We conclude that patients with T1DM and stable glycemic control display enhanced platelet activation correlating with female sex and microvascular and oxidative damages. Moreover, aspirin responsiveness is unimpaired in T1DM, suggesting that the metabolic disturbance per se is unrelated to altered pharmacodynamics. The efficacy and safety of low-dose aspirin in T1DM warrant further clinical investigation.

Topics: Adult; Albuminuria; Aspirin; Blood Glucose; Cross-Sectional Studies; Cyclooxygenase 1; Diabetes Mellitus, Type 1; Dinoprost; Epoprostenol; Female; Humans; Male; Matched-Pair Analysis; Microvessels; Middle Aged; Oxidative Stress; Platelet Activation; Platelet Aggregation Inhibitors; Sex Factors; Thromboxane A2

The purpose of the present study was to investigate the effects of green tea catechin on prostaglandin synthesis of renal glomerular and renal dysfunction in rats with streptozotocin-induced diabetes. Sprague-Dawley rats weighing 100 +/- 10 g were randomly assigned to one normal group and three groups with streptozotocin-induced diabetes. The diabetic groups were classified to a catechin-free diet (DM group), a 0.25% catechin diet (DM-0.25C group) and a 0.5% catechin diet (DM-0.5C group) according to the levels of catechin supplement in their diet. The animals were maintained on an experimental diet for 4 weeks. At this point, they were injected with streptozotocin to induce diabetes. They were killed on the sixth day. The catechin supplementation groups (DM-0.25C, DM-0.SC groups) showed a decrease in thromboxane A2 synthesis but an increase in prostacyclin synthesis, compared to the DM group. The ratio of prostacyclin/thromboxane A2 was 53.3% and 38.1% lower in the DM and DM-0.25C groups, respectively, than in the normal group. The ratio in the DM-0.5C group did not differ from that in the normal group. The glomerular filtration rate in catechin feeding groups (DM-0.25C and DM-0.5C groups) was maintained at the normal level. The urinary beta2-microglobulin content in the DM-0.5C group was significantly lower than that in the normal group. On the sixth day after induction of diabetes, the urinary microalbumin content in the DM, DM-0.25C and DM-0.5C groups had increased 5.40, 4.02, 3.87 times, respectively, compared with the normal group. In conclusion, kidney function appears to be improved by green tea catechin supplementation due to its antithrombotic action, which in turn controls the arachidonic acid cascade system.

Topics: Albuminuria; Animals; Arachidonic Acid; beta 2-Microglobulin; Catechin; Diabetes Mellitus, Experimental; Dose-Response Relationship, Drug; Epoprostenol; Glomerular Filtration Rate; Kidney Diseases; Kidney Glomerulus; Male; Prostaglandins; Random Allocation; Rats; Rats, Sprague-Dawley; Tea; Thromboxane A2

Topics: Albuminuria; Animals; Benzofurans; beta 2-Microglobulin; Cyclosporine; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Enzyme Inhibitors; Immunosuppressive Agents; Kidney; Organ Size; Pancreas Transplantation; Pyrazines; Rats; Rats, Wistar; Thromboxane A2; Thromboxane-A Synthase; Transplantation, Isogeneic

To evaluate the secretion of vasoactive factors in vascular endothelium of patients with non-insulin-dependent diabetes mellitus (NIDDM) the authors examined 31 NIDDM patients. Of them, 18 had no signs of renal involvement, 13 patients showed apparent diabetic nephropathy (DN). In the former patients the blood contained much greater content of vasodilating factor prostacyclin than of vasoconstricting factor endothelin-1 (ET-1) and thromboxan A2 (TxA2). In diabetic nephropathy the balance of vasoactive factors shifted to predominance of vasoconstrictors ET-1 and TxA2. Such rearrangement of vasoactive factors to higher quantities of vasoconstrictors in diabetes mellitus may initiate or promote progression of diabetic nephropathy with resultant spasm of afferent glomerular vessels, reduced glomerular filtration and renal blood flow rates, arterial hypertension, increased thrombogenesis. Thus, elevated levels of ET-1 and TxA2 in diabetics and their rise with progression of diabetic nephropathy are likely to act as pathogenetic factors underlying onset and progression of nephroangiopathy.

Topics: Albuminuria; Chronic Disease; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Disease Progression; Endothelin-1; Endothelium, Vascular; Epoprostenol; Female; Humans; Male; Middle Aged; Thromboxane A2

To confirm that the soluble factors produced by peripheral blood mononuclear cells (PBMC) from children with minimal change nephrotic syndrome (MCNS) enhance thromboxane (TX) A2 synthesis, we studied the urinary albumin and TXA2 metabolite excretions of rats intravenously injected with PBMC culture supernatant (PCS). Furthermore, we studied which does mainly effect on urinary albumin excretion, TXA2 metabolism in kidney or in platelet. In this study, the urinary albumin, TXB2, and 11-dehydro-TXB2 excretions of rats injected with PCS from MCNS children were remarkably increased, but this change was not observed in rats injected with PCS from children with MCNS in remission, glomerulonephritis, or healthy controls. The urinary albumin excretion of rats administered with acetylsalitylic acid before injection of PCS from MCNS children did not increase. We concluded that the soluble factors produced by PBMC from MCNS children increase urinary albumin excretion, and that the TXA2 metabolism is closely related to this effect.

Topics: Albuminuria; Animals; Aspirin; Blood Platelets; Cells, Cultured; Child; Female; Humans; Kidney Glomerulus; Leukocytes, Mononuclear; Male; Nephrosis, Lipoid; Rats; Rats, Wistar; Thromboxane A2