Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Investigations on certain hemocoagulation indices are carried out of 52 diabetics, 32 of them with diabetic nephropathy. The following indices were determined: thrombocyte numer, thrombocyte adhesion and aggregation, recalcification and heparinrecalcification time, partial thromboplastin time (PTT) and prothrombin time, coagulation retraction and thrombelastography. Data for increased blood coagulation are established in diabetics and especially in the presence of nephropathy. Most manifested are the changes in thrombocyte adhesion, in PTT, recalcification and heparin-recalcification time. Changes in thrombelastogram and the rest of the indices are less manifested. In patients with more advanced forms of nephropathy--the increased hemocoagulation is more pronounced. The changes described are considered non diabetes specific and are associated with the accompanying atherosclerosis. Those changes might indicate inclusion of anticoagulants and antiaggregating medicines in the therapeutic program of patients with diabetic nephropathy with the respective indications.
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PMID:[Changes in blood coagulation in diabetic nephropathy]. 122 99

The biological activity of thrombin and coagulation factor Xa was assessed in 62 insulin-dependent diabetic patients. A group of non-diabetic subjects of comparable age and urinary albumin excretion rate (< 30 mg/24 h) served as control subjects (group 1, n = 14). The patients were divided into three groups according to urinary albumin excretion rate. In group 2, albumin excretion rate was less than 30 mg/24 h (n = 17), in group 3 albumin excretion rate was in the range 30-300 mg/24 h (n = 20) and in group 4 albumin excretion rate was greater than 300 mg/24 h (n = 25). Compared to non-diabetic control subjects an increase in the biological activity of factor Xa was observed in all groups of diabetic patients (prothrombin fragment 1 + 2 levels were 1.14 +/- 0.38 nmol/l in group 2, p < 0.005; 1.06 +/- 0.45 nmol/l in group 3, p < 0.05 and 1.03 +/- 0.31 nmol/l in group 4, p < 0.05 vs 0.75 +/- 0.34 nmol/l in group 1). No difference in the level of antithrombin III was seen between the groups. We reconfirmed the presence of intimal dysfunction in diabetic nephropathy demonstrated by elevated transcapillary escape rate of albumin in group 4 compared with group 2 (8.9 +/- 2.0% vs 7.0 +/- 1.9%, p < 0.05). An overall positive correlation between transcapillary escape rate and prothrombin fragment 1 + 2 was found (r = 0.36, p < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Procoagulant activity and intimal dysfunction in IDDM. 774 31

Serum concentration of soluble thrombomodulin (TM) is thought to be a marker for endothelial damage. Although several studies have reported that serum TM concentrations are increased in patients with diabetes mellitus, there is little information on the physiological function of soluble TM in human plasma. To evaluate the relationship of soluble TM in plasma between coagulation and/or fibrinolysis system in patients with diabetes, we measured plasma soluble TM, protein C activity (a natural anticoagulant induced by thrombin-TM complex), prothrombin F1+2 (a direct marker of thrombin generation), and plasmin-alpha 2-antiplasmin complex (PAP) and D dimer (measures of fibrinolytic activity) in 55 patients with type 2 diabetes mellitus. The plasma concentrations of soluble TM (P<0.01), protein C activity (P<0.01), prothrombin F1+2 (P<0.05), PAP (P<0.001) and D dimer (P<0.001) were significantly higher in the diabetic patients than the 48 age-matched control subjects. The plasma concentrations of TM and PAP were obviously increased in patients with diabetic nephropathy. In the diabetic patients, the plasma concentrations of soluble TM were inversely correlated with the protein C activity (r=-0.43, P<0.005), and were positively correlated with the plasma concentrations of prothrombin F1+2 (r=0.63, P<0.0001) and the plasma PAP concentrations (r=0.30, P<0.05). The present study demonstrated that both coagulation and fibrinolysis are enhanced concomitantly in patients with type 2 diabetes mellitus, and that an increase in plasma concentration of soluble TM is associated not only with hypercoagulability but also with enhanced fibrinolysis in diabetic patients.
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PMID:Relationship between soluble thrombomodulin in plasma and coagulation or fibrinolysis in type 2 diabetes. 1102 Apr 68

Patients with end-stage renal disease dialyzed due to diabetic nephropathy are at higher risk of death due to cardiovascular complications than dialyzed non-diabetic patients. Disturbances in hemostasis may play a role in the vascular complications of diabetes mellitus. It has been postulated that TAFI-Thrombin Activatable Fibrinolysis Inhibitor, newly described glycoprotein, couples two opposite systems: coagulation and fibrinolysis. The aim of the work was to study TAFI concentration in hemodialyzed and peritoneally dialyzed diabetic and non-diabetic patients. We assessed: TAFI concentration, markers of ongoing coagulation: thrombin-antithrombin complexes, prothrombin fragments 1 + 2 (markers of TAFI activation), a marker of ongoing fibrinolysis: plasmin-antiplasmin complexes, a marker of TAFI cataliser to TAFIa-thrombomodulin using commercially available kits. All four groups studied did not differ in regard to fibrinogen, thrombomodulin, plasmin-antiplasmin complexes, and TAFI concentration. Both groups of dialyzed diabetic patients have higher concentration of markers of ongoing coagulation when compared to dialyzed non-diabetic patients. Hypercoagulable state observed in dialyzed diabetic patients may contribute to the higher cardiovascular mortality in these population.
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PMID:[Thrombin activatable fibrinolysis o inhibitor-TAFI- in dialyzed patients with diabetic nephropathy]. 1468 22

Patients dialyzed due to diabetic nephropathy are at a higher risk of death due to cardiovascular complications than dialyzed non-diabetic patients. Disturbances in hemostasis may play a role in the vascular complications of diabetes mellitus. It has been postulated that TAFI-thrombin activatable fibrinolysis inhibitor, which couples two opposite systems: coagulation and fibrinolysis, may be involved in the mechanism of vascular endothelial damage in diabetic patients. We assessed: TAFI and TAFIa, markers of ongoing coagulation: thrombin-antithrombin complexes, prothrombin fragments 1+2, a marker of ongoing fibrinolysis: plasmin-antiplasmin complexes in diabetic and non-diabetic patients on hemodialyses-HD, peritoneal dialyses-CAPD, patients with chronic renal failure with and without diabetic nephropathy on conservative treatment. Both groups of dialyzed diabetic patients have a higher concentration of markers of ongoing coagulation and TAFI activity when compared to dialyzed non-diabetic patients. Linear regression analysis showed that TAFI concentration was directly related to albumin in HD and CAPD patients without diabetic nephropathy, whereas TAFIa correlated with triglycerides, fibrinogen and leukocytes count in this group. When evaluated separately (HD, CAPD), significant correlations between TAFIa and triglycerides and fibrinogen were found only in diabetic CAPD patients. Multivariate analysis showed no correlation between TAFI and other parameters studied. In conclusion, elevated circulating TAFI and TAFIa might be a new link in the pathogenesis of impaired fibrinolysis in diabetic nephropathy, and thus atherosclerosis progression, particularly in CAPD patients. Hypercoagulable state observed in diabetic patients on conservative treatment and maintained on dialyses may contribute to the higher cardiovascular mortality in this population. In these patients there is also evidence of endothelial injury, and probably secondary activation of the coagulation cascade.
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PMID:Thrombin activatable fibrinolysis inhibitor (TAFI) and markers of endothelial cell injury in dialyzed patients with diabetic nephropathy. 1498 23

Diabetic nephropathy, a major complication of diabetes mellitus that leads to mortality, has been shown to involve a dysregulation of the coagulation system. Annexin-2, a co-receptor for plasminogen and tissue plasminogen activator on endothelial cells, is one of the molecules required to maintain the antithrombogenic properties of endothelial cells. Previously, we showed that recombinant annexin-2 protein (rAN II) modulated impaired fibrinolytic activity in the carotid arteries of rats. In the present study, to investigate its protective effects against diabetic nephropathy, rAN II was administered to KK-Ay mice, a murine model of type 2 diabetes, for eight weeks, and albuminuria, kidney size, and histological glomerular lesions were investigated. The mean weight of kidneys from KK-Ay mice treated with rAN II was significantly less than that of those treated with PBS (control) (p < 0.02). Furthermore, the level of albuminuria observed in rAN II-treated KK-Ay mice was significantly less than that of the control group (rAN II, 0.90+/-0.12 microg/day; PBS, 1.55+/-0.31 microg/day; p < 0.01); also, the area of diffuse glomerular lesions was significantly smaller (rAN II, 41.51+/-4.54%; PBS, 81.81+/-8.10%; p < 0.01). Bleeding time, prothrombin time (PT), and active partial thromboplastin time (APTT) did not significantly differ between the two groups. Our results suggest that rAN II may inhibit the progression of diabetic nephropathy in KK-Ay mice without influencing the coagulation system, indicating that annexin-2 may be considered as a possible new therapeutic tool for patients with diabetic nephropathy.
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PMID:Recombinant annexin-2 inhibits the progress of diabetic nephropathy in a diabetic mouse model via recovery of hypercoagulability. 1720 Jul 79

Diabetes mellitus is known to affect collagen in various tissues. Umbelliferone (7-hydroxycoumarin), a natural antioxidant and benzopyrone, is found in golden apple (Aegle marmelos Correa) and bitter orange (Citrus aurantium). Plant-derived phenolic coumarins have been shown to act as dietary antioxidants. In this study, we have investigated the influence of umbelliferone on collagen content and its effects on the tail tendon in streptozotocin-diabetic rats. Male albino Wistar rats (180-200 g) were made diabetic by intraperitoneal administration of streptozotocin (40 mg/kg). Normal and diabetic rats were treated with umbelliferone for 45 days. Diabetic rats had increased glucose and decreased insulin levels. Tail tendons of diabetic rats had increased total collagen, glycation and fluorescence, and decreased levels of neutral, acid and pepsin-soluble collagens. We have studied the effect of umbelliferone on haemostatic function because umbelliferone is also a coumarin derivative like the anticoagulant, warfarin. Diabetic rats had a significant decrease in prothrombin, clotting and bleeding time, and treatment with umbelliferone made these parameters almost normal. Our results show that umbelliferone controls glycaemia and has a beneficial effect on collagen content and its properties, i.e. collagen related parameters, in the tail tendon, which indicates recovery from the risk (recovery of animals from the risk of complications) of collagen-mediated diabetic polyneuropathy and diabetic nephropathy.
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PMID:Effect of umbelliferone on tail tendon collagen and haemostatic function in streptozotocin-diabetic rats. 1765 5

Sulodexide represents a novel antithrombotic agent with multiple sites of action on blood coagulation and vascular processes. The purpose of this study was to compare sulodexide and enoxaparin on anticoagulant effects, tissue factor (TF)-induced activation of platelets, inhibition of microparticle generation and to investigate their effect on heparin-induced platelet aggregation (HIPA). Sulodexide was compared with enoxaparin at equigravimetric concentrations. When compared to enoxaparin, sulodexide produced a stronger anticoagulant effect in the prothrombin time (PT), activated partial thromboplastin time (APTT), Heptest, and thrombin time (TT) assays. In addition, sulodexide had a stronger inhibitory effect on TF-mediated microparticle generation (IC(50) = 2.8 microg/ mL), P-selectin expression (IC(50) = 4.8 microg/ml), and platelet aggregate formation (IC(50) = 8.5 microg/mL) compared to higher IC(50) values with enoxaparin. Sulodexide and enoxaparin exhibited a similar effect on heparin-induced thrombocytopenia (HIT) antibody-mediated platelet activation HIPA assays. These results suggest that sulodexide is a relatively stronger anticoagulant agent than enoxaparin. Sulodexide is subcutaneously absorbed. Its ability to inhibit TF-mediated platelet activation may contribute to the observed therapeutic effects of sulodexide in microvascular vasculopathy such as diabetic nephropathy. These results also suggest that inhibition of TF activation of platelets by sulodexide may be independent of its anticoagulant effects. These results warrant further investigation of sulodexide in additional preclinical and clinical studies.
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PMID:Comparative anticoagulant and platelet modulatory effects of enoxaparin and sulodexide. 1970 18