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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The fibrinolytic system was investigated in 115 patients with maturity-onset diabetes mellitus in good metabolic control and without thromboembolic manifestations. The patients were divided into 7 groups according to the hypoglycemic therapy: diet alone, tolbutamide, glibenclamide, phenformin, combination of the last two drugs, insulin, combination of insulin and phenformin. Our results indicate that in maturity-onset diabetes both fibrinolytic activity and inhibitors of fibrinolysis are increased. The enhanced fibrinolytic activity was not affected by different hypoglycemic drugs, whereas the main antiplasmins showed wide variations in the different treatment groups. In particular, a significant reduction of alpha 2M was observed in patients on glibenclamide therapy. In conclusion, our study showed that the high fibrinolytic state seems to be a constant element in diabetes, and that the different behaviors of the fibrinolytic system, reported by various authors in patients taking different hypoglycemic drugs, could be explained by the wide range of plasmin inhibitor levels observed in these conditions.
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PMID:Hypoglycemic treatments and the fibrinolytic system in maturity-onset diabetes mellitus without thromboembolic manifestations. 685 44

An insulin-heparin complex was obtained in vitro. The hypoglycemic effect of insulin, included into this complex as compared with free insulin, was increased more than 2-fold when it was tested in animals with stable alloxane diabetes. Contrary to insulin, administration of the insulin-heparin complex increased the anticoagulation properties of blood and exhibited the non-enzymatic fibrinolytic activity towards the unstabilized fibrin both in presence or in absence of inhibitors of fibrinolysis, caused by plasmin.
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PMID:[Insulin-heparin complex, its physiological properties]. 702 17

The case of a 26 year old woman who had been taking tranexamic acid to prevent uterine bleeding due to an IUD and who died from thrombosis of the left internal carotid artery is reported. The patient's father had died at age 54 of myocardial infarction. Otherwise the family history was entirely negative for thromboembolic disease. The patient was a mild smoker. She had been previously healthy and in particular, she was not affected with hypertension, diabetes, or dyslipidemia. She had carried to term 2 uncomplicated pregnancies. 40 days prior to hospital admission her gynecologist had inserted an IUD. The insertion of the IUD was followed by persistent uterine bleeding, and for this reason she began treatment with tranexamic acid (1.5 g/daily). Uterine bleeding persisted despite this treatment, and the IUD was removed. Because of persistence of a mild uterine bleeding, tranexamic acid was continued. 2 hours before admission the patient suddenly presented a left sided hemiparesis with disarthria and vomiting. On admission she was stuporous. The left side of her face drooped and the strength of the left arm and leg was markedly decreased. Both arm and leg reflexes were symmetrical. Her blood pressure was 110/70. An electroencephalogram on arrival confirmed a right sided cerebral lesion. Subsequently the patient's condition deteriorated rapidly. She developed a full left hemiplegia and became deeply comatose. A CAT scan performed 4 hours after admission showed no abnormalities. A CAT scan performed 3 days after admission showed a large cerebral infarction involving nearly the whole right cerebral hemisphere. The patient's condition remained essentially unchanged until she died 6 days after admission. Permission for autopsy was refused. Antifibrinolytic drugs competitively inhibit plasminogen activators and noncompetitively plasmin. Thromboembolic complications after the administration of antifibrinolytic drugs have long been recognized. The use of IUDs is often associated with troublesome uterine bleeding and particularly excessive menstrual bleeding. To avoid these complaints, antifibrinolytic drugs are increasingly used.
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PMID:Tranexamic acid, intrauterine contraceptive devices and fatal cerebral arterial thrombosis. Case report. 710 62

Glucose, when incubated with fibrinogen, binds covalently to that protein. The reaction is non-enzymatic in type and is directly dependant on the time of incubation, temperature and pH. Glucosylation of fibrinogen is not altered by preincubation with aspirin. No preferential glucosylation of fibrinogen, fibrinogen chains or plasmin digestion products XYDE could be demonstrated, suggesting that glucose binding occur at several different sites. No abnormality of thrombin clotting or stability of glucosylated fibrinogen could be detected. These findings are discussed in relation to the previously described abnormalities of fibrinogen metabolism in diabetes mellitus.
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PMID:Non-enzymatic glucosylation of fibrinogen. 727 78

Inappropriate vascular smooth-muscle cell (VSMC) growth is the hallmark of vascular pathology in essential hypertension and diabetic macroangiopathy, whereas platelets constitute an important regulator of vessel wall homeostasis because of their content of various growth factors. Numerous abnormalities exist in platelet functions in diabetes and hypertension, such as enhanced activity and altered adhesion and aggregation. Increased thromboxane (TX2) production is characteristic of diabetes, and an elevation of intracellular free Ca2+ is found in platelets of hypertensive patients. By studying the growth patterns of VSMC from spontaneously hypertensive rats (SHRs) vs. those obtained from their normotensive counterparts, Wistar-Kyoto (WKY) rats, we have demonstrated that VSMC from SHRs exhibited a higher specific growth rate, abnormal contact inhibition, and accelerated entry into the S phase of the cell cycle. Moreover, they were hyperresponsive to many growth factors such as calf serum, epidermal growth factor (EGF), platelet-derived growth factor (PDGF), transforming growth factor beta 1 (TGF beta 1), and insulin. Additive effects were observed for EGF and PDGF or EGF and insulin. These intrinsic growth anomalies in cells of hypertensive origin persist in culture indicating their putative primary role in the pathogenesis of hypertension. Endogenous TGF beta 1 revealed an augmented expression of its message levels in SHR VSMC, the difference in mRNA between both strains being more pronounced at high cell density. Further, TGF beta 1 protein synthesis and secretion in VSMC culture were confirmed by immunoprecipitation of de novo labeled TGF beta 1. At high cell density, which most likely represents the physiological state of VSMC, plasmin, an activator of TGF beta 1, significantly stimulated DNA synthesis of VSMC in both strains. The reverse effect was obtained at low cell density. Yet, the fold stimulation was higher in WKY rats, suggesting that TGF beta 1 may be partially activated in SHR VSMC. This is supported by the inhibition of baseline DNA synthesis by TGF beta 1 neutralizing antibody in VSMC of hypertensive origin and not of normotensive controls. TGF beta 1 antisense oligodeoxynucleotide (ODN) nearly normalized the increased proliferation of SHR VSMC in culture. On the other hand, growth-promoting activity (GPA) in platelets of either diabetic or hypertensive patients was higher than in platelets of healthy controls and was found to be normalized by intensive insulin therapy in insulin-dependent diabetic patients. In hypertensive patients, however, hydrochlorothiazide (HCTZ)--even in low doses (25 mg/day)--enhanced the GPA in platelets, whereas other antihypertensive agents such as indapamide, atenolol, and captopril, had neutral effects.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Platelets, growth factors, and vascular smooth-muscle cells in hypertension and diabetes. 750 64

Patients with diabetes are predisposed to microvascular disease. In the retina and brain, this is characterized by neovascularization and new capillary formation. Because of the potential importance of plasmin generation in these processes, we evaluated the effect of elevated glucose concentrations on expression of plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA), and urokinase (uPA) in cultured bovine brain endothelial cells (BBEC) versus cultured bovine aortic endothelial cells (BAEC). We observed that BBEC PAI-1 mRNA levels were decreased fivefold in cells cultured in media containing 20 mM glucose compared with BBEC cultured in media with 5.5 mM glucose, whereas expression of PAI-1 mRNA in BAEC, bovine mesenteric endothelial cells, and human umbilical vein endothelial cells was not modulated under these conditions. Expression of PAI-1 protein was also inhibited by growth of BBEC in elevated glucose, but the effect was less marked than at the mRNA level. Elevated glucose did not decrease expression of PAI-1 protein by BAEC. Withdrawal of acidic fibroblast growth factor enhanced expression of PAI-1 mRNA and protein in BBEC. Expression of tPA mRNA was not affected by the glucose concentration of the medium, and uPA mRNA was not detected in our BBEC cultures. A decrease in the local tissue activity of PAI-1 by elevated glucose concentrations, with no effect on tPA or uPA expression, would lead to an increase in the plasmin activity and thereby predispose neural tissues, such as the cerebrum and retina, of diabetic patients to neovascularization.
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PMID:Plasminogen activator inhibitor-1 expression by brain microvessel endothelial cells is inhibited by elevated glucose. 751 64

To better understand the abnormalities of red blood cell (RBC) hyperaggregation and elevation of fibrinogen during diabetes mellitus, we have studied the effect of plasminogen activation on RBC aggregation phenomenon. The plasminogen was activated in vitro by adding streptokinase in blood suspensions of 26 diabetic patients and 11 healthy subjects. RBC aggregation measurements were performed by means of the Sefam erythroaggregometer. Results show decreases in either RBC aggregation and fibrinogen level as a result of the plasminogen activation in blood suspensions of healthy subjects. In blood suspensions of diabetic patients, although RBC aggregation and fibrinogen level are decreased following the plasminogen activation, however decreases are less pronounced than those obtained in blood suspensions of healthy subjects. These results mean a decreased degradation of fibrinogen by plasmin in diabetes mellitus and could explain in part the excess of fibrinogen and so the hyperaggregation tendency of red blood cells.
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PMID:[Plasminogen activation and erythrocyte aggregation in diabetic patients]. 779 4

Lipoprotein(a) constitutes a macromolecular complex in human plasma that combines structural features from the blood clotting and the lipoprotein systems. Aside from the discovery of lipoprotein(a) [Lp(a)] as a potential independent risk factor for premature cardiovascular disease its physiological role and activity remains obscure. Since the site of catabolism has not yet been fully characterized, there is intensive search for factors which influence plasma Lp(a) levels. Several clinical conditions and metabolic states have been identified to be added to the disorders of the lipid metabolism itself that modulate Lp(a) plasma levels. Diseases of the kidney and their accompanying factors (proteinuria and nephrotic syndrome) as well as end-stage renal disease and their treatment modalities (hemodialysis, peritoneal dialysis, and kidney transplantation) have all been found to increase Lp(a) plasma levels substantially. Fluctuations in Lp(a) also seem to occur in states of hormonal changes, such as in diabetes mellitus, after estrogen treatment, and during pregnancy. Recently a plausible mechanism for the atherogenic activity of Lp(a) has been ascribed to the inhibiting effect of Lp(a) on plasminogen activation, thus decreasing plasmin formation which in turn reduces the activation of transforming growth factor beta, a potent inhibitor of smooth muscle cell proliferation. Lp(a) exerts its pathological effect at plasma levels in the range of 20-30 mg/dl. Therefore, it seems mandatory to quantitate Lp(a) levels in patients who are at risk of developing progressive atherosclerotic disease to identify those with high levels of this unique atherogenic lipoprotein.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lipoprotein(a): new insights into an atherogenic lipoprotein. 781 11

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

Human peripheral blood monocytes isolated by centrifugation with Mono-Poly resolving medium, and human alveolar macrophages obtained by lung lavage during fiberoscopic bronchoscopy, were cultured in RPMI containing 2% foetal calf serum. The cultures were exposed to modified human proteins: alpha-1-antitrypsin cleaved with papain, fibrinogen degradation products (fraction D) purified from plasmin digest, and non-enzymatically glycosylated (glycated) serum albumin. Conditioned macrophage media were tested for the contents of acute phase cytokines by bioassay with hepatoma cells, and the concentration of interleukin-6 was determined with ELISA. Modified proteins stimulated macrophages to produce acute phase cytokines and the response was not abrogated by polymyxin B in distinction to stimulation of macrophages by endotoxin. Our data indicate that some proteolytically damaged proteins or the end glycosylation products formed in pathological states (acute inflammation, diabetes) may be responsible for the appearance of cytokines in the circulation.
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PMID:Origin of circulating acute phase cytokines: modified proteins may trigger IL-6 production by macrophages. Preliminary report. 804 10


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