Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the relationships between albuminuria, tissue factor-induced coagulation, and endothelial cell dysfunction in 67 patients with non-insulin-dependent diabetes mellitus (NIDDM) who were divided into three groups on the basis of their urinary albumin excretion rate (AER). To assess the early phase of tissue factor-induced coagulation, activated factor VII (FVIIa) levels in plasma were measured by a direct fluorogenic assay. As markers of endothelial cell dysfunction, levels of von Willebrand factor (vWF), tissue-type plasminogen activator-plasminogen activator inhibitor-1 (TPA-PAI-1) complex, PAI-1, and tissue factor pathway inhibitor (TFPI) were measured. FVIIa levels were increased in normoalbuminuric NIDDM patients (AER < 15 micrograms/min) when compared with normal control subjects. This FVIIa increase was accompanied by an increase in thrombin-antithrombin III complex (TAT) levels, indicating increased activation of coagulation even in normoalbuminuric patients. In NIDDM patients with microalbuminuria (AER = 15-200 micrograms/min), the FVIIa level, the FVIIa-FVII antigen (Ag) ratio (an indicator of activation of FVII zymogen to FVIIa), and the TAT level were further increased. This group also had higher levels of endothelial cell-derived factors (vWF, TPA-PAI-1 complex, and PAI-1) than the control group. The levels of endothelial cell-derived factors (including TFPI) were highest in the NIDDM patients with overt albuminuria (AER > 200 micrograms/min). In all 67 diabetic patients, AER showed a strong positive correlation with FVIIa (r = .574, P < .0001) and a weakly but still significant correlation with FVIIa-FVII:Ag (r = .365, P = .01), vWF (r = .315, P < .01), and TAT (r = .323, P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Activation of tissue factor-induced coagulation and endothelial cell dysfunction in non-insulin-dependent diabetic patients with microalbuminuria. 762 4

Vascular diseases and related complications still represent the main cause of death. In diabetes neuropathy, nephropathy, retinopathy and disturbed nutritive tissue perfusion result from reduced capillary microcirculation. These disturbances are diabetes specific, whereas macroangiopathy does not differ structurally from atherosclerotic lesions of non-diabetic subjects, but leads to accelerated cerebral, coronary and peripheral artery disease. Occurrence of life terminating thrombotic events which are superimposed to those vascular lesions is increased. Thus, morbidity and mortality of diabetes depend mainly on vascular complications. Normal blood flow is a prerequisite of adequate organ perfusion and results from vasomotion, plasma components, corpuscular blood elements, vascular architecture and the undisturbed interaction of these components at the endothelial interface. Functional thromboresistance of the endothelial layer is reduced in the diabetic state. Increased intravascular thrombin generation, reduced fibrinolytic potential and hyperactive platelets lead to a prethrombotic state. This thrombotic diathesis raises the permanent danger of acute flow disruption. Activated platelets operate by three mechanisms: 1. microembolization of the capillaries; 2. local progression of preexisting vascular lesions by secretion of constrictive, mitogenic, and oxidative substances; and 3. trigger of the prognosis limiting arterial thrombotic event. We were able to show that the increased functional properties of diabetic platelets result from the primary release of larger platelets with enhanced thromboxane formation capacity and increased numbers of functional glycoprotein receptors GPIB and GPIIB/IIIA which are synthesized in the megakaryocytes. The megakaryocyte-platelet system is turned on in diabetes mellitus.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:The activated megakaryocyte-platelet-system in vascular disease: focus on diabetes. 766 Jan 37

Magnesium deficiency and its association with platelet hyperreactivity has been well recognised in a variety of diseases including myocardial infarction, preeclampsia, and diabetes. In order to investigate potential effects of intravenous Mg2+ supplementation, platelet function was studied by measurements of in vitro bleeding time (BT) and of fibrinogen (Fg)-mediated aggregation of washed platelets. In addition, the effect of Mg2+ on platelet adhesion onto immobilised Fg, on Fg binding to activated platelets, and on surface expression of GMP-140 or GP53 was evaluated. Mg2+ (4 mM) prolonged in vitro BT by 30% and inhibited Fg-mediated aggregation significantly, independent of the agonist used to initiate platelet aggregation (ADP, collagen, epinephrine, thrombin, phorbol ester). Adhesion of resting platelets to immobilised Fg was reduced by 50% in the presence of 2 mM Mg2+. Moreover, Mg2+ reduced Fg binding to ADP- or collagen-stimulated platelets as well as surface expression of GMP-140 with an IC50 of approximately 3 mM. Intravenous administration of Mg2+ to healthy volunteers inhibited both ADP-induced platelet aggregation (p < 0.05) by 40% and binding of Fg or surface expression of GMP-140 by 30% (p < 0.05). Thus, pharmacological concentrations of Mg2+ effectively inhibit platelet function in vitro and ex vivo.
 ...
PMID:Effects of magnesium on platelet aggregation and adhesion. Magnesium modulates surface expression of glycoproteins on platelets in vitro and ex vivo. 774 Apr 63

Vascular endothelial injury associated with arterial narrowing leads to platelet adhesion and aggregation at the site of endothelial injury and to the local accumulation of several mediators that promote platelet aggregation and vasoconstriction, including thromboxane A2, serotonin, adenosine diphosphate, platelet activating factor, oxygen-derived free radicals, activated thrombin, and tissue factor. At the same sites of endothelial injury, there is a reduction in absolute or relative amounts of the endogenous inhibitors of platelet aggregation and vasoconstriction, including prostacyclin, endothelium-derived relaxing factor (nitric oxide), and tissue plasminogen activator; the loss of the effects of the endogenous inhibitors preventing platelet aggregation and vasoconstriction helps to create a prothrombotic and vasoconstrictive environment. Endothelial injury occurs as a result of atherosclerotic plaque fissuring or ulceration, flow shear stress, hypertension, diabetes mellitus, immune complex deposition, infection, and mechanical injury in the form of diagnostic and therapeutic catheterization. Endothelial injury and the accumulation of platelet- and other cell-derived mediators promotes neointimal proliferation in an exaggerated wound-healing response, resulting in further anatomic narrowing of artery in the subsequent days and weeks. Future methods that may prove useful in protecting the individual with these vascular problems from acute myocardial infarction and its consequences are inhibition of multiple mediators of platelet aggregation and vasoconstriction, restoration of the presence of the normal endogenous inhibitors of platelet aggregation and vasoconstriction, and/or rapid therapeutic regeneration of the injured endothelium.
 ...
PMID:Conversion from chronic to acute coronary heart disease syndromes. Role of platelets and platelet products. 778 65

The aim of this study was to examine whether there was a relationship between haemostatic factors and ultrasound-assessed morphology of the common carotid artery and cardiovascular disease in 57- to 77-year-old men at high risk for atherosclerotic disease (hypertension and at least one of the following risk factors: hypercholesterolaemia, smoking, diabetes mellitus). They were divided into one group with (n = 59) and one group without (n = 70) manifest cardiovascular disease. An age-matched reference group with no cardiovascular risk factors was used as a comparison (n = 51). Significant associations, independent of smoking, were found between plasma fibrinogen and both the maximal intima-media thickness and the occurrence of plaque in the high-risk group. High-risk patients with clinical signs of cardiovascular disease had higher levels of plasma fibrinogen and prothrombin 1 + 2 fragment compared with both high-risk patients without concomitant cardiovascular disease and low-risk subjects. Plasminogen activator inhibitor, von Willebrand factor and thrombin/antithrombin complex were increased in the high-risk group with signs of cardiovascular disease in comparison with the low-risk group. In conclusion the results indicate that plasma fibrinogen may be operative in the development of atherosclerosis. Clinical signs of cardiovascular disease were associated with increased plasma levels of fibrinogen, von Willebrand factor, plasminogen activator inhibitor, thrombin/antithrombin complex and prothrombin 1 + 2 fragment.
 ...
PMID:Carotid artery wall morphology, haemostatic factors and cardiovascular disease. An ultrasound study in men at high and low risk for atherosclerotic disease. 789 27

To elucidate a role of tPA, uPA and PAI-1 for the development of diabetic glomerulosclerosis, the effect of high glucose concentration on the production of both basal and thrombin-mediated tPA, uPA and PAI-1 antigens from human mesangial cells was investigated. The culture of mesangial cells in the presence of high glucose (33 mM) for 11 days resulted in an increase in the synthesis of tPA and uPA when compared with that in normal glucose concentration (5 mM). In contrast, the cells grown in high glucose produced less PAI-1 than those in normal glucose. Thrombin stimulated dose-dependently the production of tPA, uPA and PAI-1 from the cells grown in either 5 or 33 mM glucose. However, the magnitude of the increase in tPA, uPA and PAI-1 from the cells grown in high glucose was less than that in normal glucose. These results suggest that the plasmin activity in mesangial cells may increase under a high glucose condition, leading to increased proteolysis of mesangial matrix. In addition, either fibrinolysis or proteolysis mediated by thrombin may be altered by high glucose concentration. Therefore, it is postulated that the turnover of mesangial matrix may be increased in diabetic nephropathy.
Diabetes Res Clin Pract 1994 May
PMID:A high concentration of glucose alters the production of tPA, uPA and PAI-1 antigens from human mesangial cells. 792 84

Increased platelet aggregation and secretion in response to various agonists has been described in both diabetic humans and animals. Alterations in the platelet membrane fatty acid composition of phospholipids and changes in the prostacyclin and thromboxane formation could only partly explain the altered platelet function in diabetes. In the present study, we have examined the role of phosphoinositide turnover in the diabetic platelet function. We report alterations in 2-[3H] myo-inositol uptake, phosphoinositide turnover, inositol phosphate and diacylglycerol (DAG) formation, phosphoinositide mass, and phospholipase C activity in platelets obtained from streptozotocin (STZ)-induced diabetic rats. There was a significant increase in the 2-[3H] myo-inositol uptake in washed platelets from diabetic rats. Basal incorporation of 2-[3H] myo-inositol into phosphatidylinositol 4,5-bisphosphate (PIP2), phosphatidylinositol 4-phosphate (PIP) or phosphatidylinositol (PI) in platelets obtained from diabetic rats was, however, not affected. Thrombin stimulation of platelets from diabetic rats induced an increase in the hydrolysis of [32P]PIP2 but indicated no change in the hydrolysis of [32P]PIP and [32P]PI as compared to their basal levels. Thrombin-induced formation of [3H]inositol phosphates was significantly increased in both diabetic as well as in control platelets as compared to their basal levels. This formation of [3H]inositol phosphates in diabetic platelets was greater than controls at all time intervals studied. Similarly, there was an increase in the release of DAG after thrombin stimulation in the diabetic platelets.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Platelet phosphoinositide turnover in streptozotocin-induced diabetes. 793 87

The effects of contraceptive steroids on the expression of endothelial homeostasis were examined by direct and indirect measures in women with insulin-dependent diabetes mellitus (IDDM) in a prospective nonrandomized controlled study. Study subjects were 13 women with uncomplicated IDDM treated with a monophasic combination of 30 micrograms ethinyl estradiol and 75 micrograms gestodene for 12 consecutive cycles and 13 women of comparable diabetic status as control. During the study period, none of the participants developed increased renal albumin excretion, which was used as a direct measure of endothelial function. In the indirect assessment of endothelial function, we found a proportionate increase in plasma levels of thrombin-antithrombin III (TAT) complexes and D-dimer during treatment. Hormonal intake was followed by decreased antigen concentrations of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor (type 1 [PAI-1]), whereas the activities of t-PA and PAI-1 were unchanged. Plasma levels of plasminogen and histidine-rich glycoprotein (HRG) increased and decreased, respectively, whereas an increase in von Willebrand factor was observed in the treatment group. No significant changes in direct or indirect measures were observed in the control group during the observation period of 12 months. In conclusion, no adverse effect on endothelial function was demonstrated by direct measures, but our findings suggest that a procoagulant state, compensated by enhanced activity of the fibrinolytic system, is induced by hormonal treatment. Clinical and metabolic monitoring is recommended if the use of oral contraceptives in women with IDDM is extended.
 ...
PMID:Assessment of endothelial function during oral contraception in women with insulin-dependent diabetes mellitus. 796 93

Thrombomodulin is an endothelial cell surface glycoprotein that forms a 1:1 complex with thrombin. In this form, thrombin can activate approximately 1,000-fold more protein C than thrombin alone and does not activate coagulation factors, V and VIII, and platelets. Activated protein C inactivates factors Va and VIIIa. Thus thrombomodulin converts thrombin from a procoagulant protease to an anticoagulant. The soluble thrombomodulin present in human urine and plasma appears to represent a truncated form that lacks the transmembrane and cytoplasmic domains of tissue thrombomodulin. The plasma level of thrombomodulin has been used as a marker for endothelial injury in vivo. Elevated levels of soluble thrombomodulin were reported in the plasma from the patients with disseminated intravascular coagulation, adult respiratory distress syndrome (ARDS), and diabetes mellitus retinopathy.
 ...
PMID:[Soluble thrombomodulin: as a marker of endothelial injury]. 805 97

We measured various coagulable factors and molecular markers in plasma and serum in the disease group including DIC, DIC suspect, thrombosis, acute myocardial infarction, angina pectoris, sepsis, malignant tumor and type II diabetes and the healthy subject group, and surmised the intravascular coagulative-fibrinolytic activity in each disease group compared with the healthy group. Additionally we selected parameters useful for early detection of the pre-thrombotic state and hypercoagulable state. As a result, of the parameters for the coagulative system, those considered useful were the assay of soluble fibrin monomer complexes using the synthetic substrate (FM.Oita), assay of soluble fibrin monomer complexes using HPLC(SFMC.Oita) and thrombin-anti-thrombin III complex (TAT) in this order. Of the parameters for the fibrinolytic system, those considered useful were FDP assay using ELISA (FDP.Oita) and plasmin-alpha 2 plasmin inhibitor complex (PIC). This FDP.Oita had a considerably high detection sensitivity compared with the FDP assay (Diayatron Co.) using the latex photometric immunoassay which has been commercially available. When measurement was made with plasma and serum in the subject disease group as the sample by the high sensitivity assays mentioned above, it was made clear that both the coagulative activity and fibrinolytic activity are increased, albeit with some differences in intensity, in all the disease groups compared with the healthy group. In order for the hypercoagulable state and pre-thrombotic state to be detected, it is important to know the balance between the coagulative activity and fibrinolytic activity. According to the results of the present experiment, a significant directly proportional correlation was recognized between FM.Oita and FDP.Oita and between TAT and FDP.Oita. Therefore, examination of these ratios will be a more detailed indicator of coagulative-fibrinolytic activity than the TAT/PIC ratio, PAI-1/TPA ratio and ATIII/alpha 2 PI ratio hitherto in use. If useful molecular markers such as FM.Oita are measured over time in various cases and these data are compiled and analyzed statistically, it will not be long before the criteria for the hypercoagulable state and pre-thrombotic state are established.
 ...
PMID:[Molecular marker for detecting hypercoagulable state]. 810 79


<< Previous 1 2 3 4 5 6 7 8 9 10