Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two thrombolytic agents are mainly used in patients: streptokinase (SK) and urokinase (UK). UK from human origin is an endopeptidase which is able to convert plasminogen into plasmin. UK is only secreted by the kidney and is only found in urine which is presently the only source of extraction. Studies in man have shown that UK produces a highly reproducible state of enhanced plasma thrombolytic activity with a high fibrinolysis/fibrnogenolysis ratio and a lack of toxicity and antigenicity. The half life in Animal is short as well as the duration of fibrinolytic activity in Man. In clinical experience, positive results have been reported in pulminary embolism while the issues in myocardial infarction are controversial. Suggestive results have been registered in deep vein thrombosis, in ophthalmologic field and in desobstruction of arterio-venious shunts. No evident benefit has been noted in cerebral vascular disease. Up to now, UK has been very well tolerated.
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PMID:[Urokinase. Biochemical therapeutical and therapeutical data (author's transl)]. 6 58

The thrombogenic mechanism of arterial grafts has been studied by determining the relative utilization of platelets, fibrinogen and plasminogen by human arterial prostheses, and by direct examination of arterial grafts in a baboon model. Forty-one survival and turnover measurements of (51)Crplatelets, (131)I-fibrinogen and (125)I-plasminogen in ten patients with aortofemoral knitted Dacron prostheses demonstrated platelet consumption after graft placement (platelet survival 4.2 days +/- 0.5 and turnover 68,000 plat/ul/day +/-10,000 compared with 8.2 days +/- 0.3 and 35,000 plat/ul/day +/- 5,000 respectively for control subjects with stable vascular disease, p < 0.01). In vitro platelet function test results were normal. Platelet consumption was interrupted by dipyridamole or a combination of dipyridamole and acetylsalicylic acid, and platelet survival normalized spontaneously during nine months postoperatively. No significantly increased consumption of fibrinogen or plasminogen was found in these patients with arterial grafts. Placement of impervious knitted Dacron velour aortic grafts in baboons reproduced platelet consumption that progressively normalized over six weeks postoperatively. Platelet survival measurements correlated directly with endothelial cell coverage of the graft luminal surface in these animals implying that endothelialization of the graft surface was also occurring postoperatively in patients.
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PMID:Platelet consumption by arterial prostheses: the effects of endothelialization and pharmacologic inhibition of platelet function. 41 28

The defibrinating agent ancrod has had limited clinical trial, but appears to give no advantages over heparin. Intravenous infusion of dextran, a glucose polymer, has been shown to have an antithrombotic effect in many experimental models of thrombosis. However, the evidence that dextran is a clinically valuable antithrombotic drug is conflicting. A number of controlled randomized studies have shown that dextran can prevent postoperative venous thromboembolism when a large volume of dextran 40 or 70 was infused rapidly during and after surgery. However, blood volume expansion during dextran treatment prohibits its use in patients with reduced cardiac reserve, and infrequent though sometimes severe, allergic reactions have been reported. Evidence that dextran is of value for the treatment of venous or arterial thromboembolism comes from uncontrolled studies and is not convincing. Many compounds have been shown to inhibit platelet function in vitro but only five of these drugs have been extensively evaluated as prophylactic or therapeutic antithrombotic agents in man. These are aspirin, sulphinpyrazone, dipyridamole, hydroxychloroquine and clofibrate. They have been evaluated mainly in patients with cerebral vascular disorders, coronary artery disease, peripheral artery ischaemia, venous thromboembolism, prosthetic heart valves, and in patients with arteriovenous shunts. The evaluation of the clinical effect of the platelet function suppressing drugs is in its early stages, but they appear to differ from each other in the spectrum of their clinical effectiveness, and they may be more effective in arterial than in venous thromboembolic disorders. Their role in the management of cerebral vascular disease and coronary artery disease is still uncertain, and should be clarified by the results of a number of multi-centre, prospective, randomized studies which are currently in progress. Three types of thrombolytic drugs have been evaluated clinically; the plasminogen activators streptokinase and urokinase, proteolytic enzymes such as plasmin, and agents which increase the level of endogenous plasminogen activator (e.g. anabolic steroids). Of these, the plasminogen activators now have a definite place in clinical practice. The plasminogen activators accelerate the lysis of recent venous thrombi and pulmonary emboli, and of arterial thrombi or emboli. Thrombolytic therapy with these agents should be considered particularly in patients with recent major pulmonary embolism, as lysis of recent emboli is rapid and substantial. It should also be considered in patients with recent extensive venous thrombosis, because total lysis of venous thrombi has been reported to result in long-term preservation of valve function, and is likely to prevent postphlebitic syndrome, though this has not been proven. However, plasminogen activator therapy carries a higher risk of bleeding than heparin treatment...
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PMID:Antithrombotic drugs: part II. 78 6

Endoglycan, a heparan-dermatan sulphate association, is a highly purified heparinoid extracted from porcine intestinal mucosa. The aim of our study was to investigate the fibrinolytic system in a group of healthy controls and vascular disease patients, before and after endoglycan administration "per os". All the patients had a reduced basal fibrinolytic activity. The tests carried out were PT, PTT, FDP, Euglobulin Lysis Time (ELT), fibrinogen, plasminogen, alpha 2-antiplasmin, alpha 2-macroglobulin and t-PA activity assayed with a chromogenic method. After endoglycan administration, we have shown a significant shortening of ELT with complete normalization during the treatment. A fibrinogen decrease and either plasminogen or alpha 2-antiplasmin increase was seen. This was shown in normals too, however to a lesser extent. During therapy most of the healthy subjects, but only some patients, showed increased t-PA levels. Before and during treatment, significantly higher t-PA levels were seen in the control group as compared to the patients group. Reduced t-PA release was seen in our vascular disease patients. In conclusion, endoglycan "per os" appears to exert a stimulatory effect on the fibrinolytic system.
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PMID:Fibrinolytic effect of a particular glycosaminoglycan (endoglycan) per os on normals and in patients with chronic artery disease. 170 5

Impaired function of the fibrinolytic system might be involved in the development of vascular disease and thromboembolic complications in diabetic patients. We studied kinetics of plasmin formation using t-PA and Pg purified from the plasma of three individual uncontrolled type I diabetic patients. Activation of diabetic Pg by normal t-PA in the presence of stimulating CNBr fragments of fibrinogen exhibited a prolonged lag phase (30 to 60 minutes) until maximally stimulated plasmin formation occurred (normal, 5 to 15 minutes) and substrate inhibition at Pg concentrations more than 10 to 30 nM. When normal Pg was activated by diabetic t-PA in the presence of CNBr-f, differentiation between lag phase and phase of maximal plasmin formation was not possible (activation time was 2 hours) and a high Km (7.5 microM) was calculated. After normalization of metabolic parameters in the patients studied, functional properties of t-PA and Pg improved. Km of diabetic t-PA returned to normal values (0.02 to 0.09 microM) and for diabetic Pg the prolonged lag phase was shortened, indicating that the functional abnormalities were reversible and possibly caused by metabolically induced changes (such as nonenzymatic glucosylation) in the t-PA or plasminogen molecule. We also studied the effect of in vitro glucosylation on functional properties of Pg. Similar, but less pronounced substrate inhibition as with diabetic Pg was observed when this glucosylated Pg was activated by t-PA in a system stimulated by CNBr fragments of fibrinogen. Therefore nonenzymatic glucosylation might explain, at least in part, functional abnormalities observed with Pg from diabetic patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasminogen activation in diabetes mellitus: kinetics of plasmin formation with plasminogen and tissue plasminogen activator from diabetic donors. 183 61

Hemostatic disorders in coronary heart disease and cerebrovascular disease patients were examined by studying two groups of prothrombotic and prethrombotic markers. Sixty subjects (28 male, 32 female aged 64 +/- 6 years) were included in the study of which 30 suffered from coronary heart disease and 30 from cerebral vascular disease; the first group was subdivided into those subjects with quiescent preinfarction angina (21 cases) and those with acute myocardial infarction (9 cases), whereas the second group was subdivided into subjects with cerebral stroke (20 cases) and those with TIA (10 cases). Each subject underwent an assay to assess fasting blood levels of fibrinogen, factor VII, antithrombin III (using a chromogenic method), plasminogen tissue activator, beta-thromboglobulin and dimer-D (ELISA method) 24 hours after being admitted to hospital. From an analysis of results it was observed that of the four prothrombotic markers used, fibrinogen and factor VII showed a generic increase in comparison to coronary heart disease and cerebrovascular disease patients; this was paralleled by significant reduction of antithrombin III; differences were even more marked and significant in acute thrombo-occlusive (infarction, stroke) compared to functional forms (angina, TIA). In line with other studies, the Authors favour an irritative type endothelial response leading to a marked and surprising increase of tPA. The two prothrombotic markers (BTG, D-D) also showed a thrombotic development in the two groups of patients examined with more significant findings in the occlusive forms (infarction, stroke) in comparison to transitory forms. On the basis of these and other published results the Authors confirm the usefulness of monitoring prothrombotic markers (fibrinogen, factor VII, AT III) in apparently normal subjects with or without risk factors or with slight initial signs of arteriosclerotic disease; these call for longitudinal or cross-sectional studies of an epidemiology type, in addition to isolated assay for a generic assessment of the patient's biological status, even if it is not yet possible to elaborate a protocol for the certain and specific diagnosis of a thrombophilic condition. The value of prethrombotic markers is apparent in the acute occlusive stage of the disease as a form of prognostic and therapeutic monitoring, and in preinfarction and above all silent transitory forms where, together with the use of other techniques (Holter), it provides interesting openings for confirming the diagnosis of an in vivo microthrombotic genesis and the consequent introduction of antithrombotic drug therapy.
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PMID:[The thrombophilic status and ischemic cardiopathy]. 195 44

Picotamide is the most interesting compound of 4-OH isophthalic acid. It is effective in vitro and in vivo. Picotamide induces inhibition of platelet aggregation: it is a thromboxane synthetase inhibitor and a thromboxane receptor antagonist. Picotamide causes cyclic endoperoxide accumulation and diverts their metabolism toward PgI2 synthesis in endothelial cells. PGI2 stimulates the adenylate cyclase with cAMP synthesis which makes platelets less sensitive to aggregatory stimulation. Picotamide induces enhancement of fibrinolytic activity, with significant reduction in the level of circulating plasminogen but in the same time it does not affect antithrombin III and FDP levels. In the present study picotamide or placebo were administered in a double blind trial at 600 mg daily for six months to 51 patients effected by diabetic macro and/or microangiopathy. The patients were 38 men and 13 women, the age was between 20 and 80 years (mean age 62.34). Twenty-seven patients were affected by type I diabetes and 24 by type II diabetes. Twenty-three of these patients presented macro-angiopathic lesions, 9 only microangiopathic lesions and 13 both. Twenty-five patients received picotamide and the other 25 an identical placebo for six months. One patient manifested myocardial infarction during the wash-out period and failed to enter the study. The following determinations were carried out: at T0 clinical examination, Doppler ultrasonography, Winsor Index, laboratory parameters; after 90 days (T90) clinical examination and Winsor Index and after 180 days (T180) were repeated photoplethysmography and clinical parameters too. Patients were not only evaluated for the vascular disease of lower extremities, but also for the other complications of diabetes, as retinopathy, nephropathy, cardiac and cerebrovascular disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Picotamide: prevention and therapy of diabetic vasculopathies. A double-blind clinical study]. 214 11

The authors examined in a group of 165 diabetics and 50 healthy subjects the basal fibrinolytic activity after venostasis and in a selected group of diabetics also after stimulation with adiuretin. They revealed not only a retarded fibrinolytic activity in diabetics with angiopathy, as compared with healthy subjects, but also a significant deterioration of the response in this group to stimuli such as venostasis and adiuretin. The authors draw attention to the fact that changes of the fibrinolytic activity which were more marked in diabetics with angiopathy may be conditioned not only by age, the duration of the disease and the elevated inhibitors of plasma fibrinolysis but also by a poorer release of the tissue activator plasminogen.
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PMID:[Changes in fibrinolysis in diabetes mellitus]. 233 14

In 75 patients with acute cerebral vascular disease (infarction 43, TIA 4, cerebral hemorrhage 25, subarachnoid hemorrhage 3), the plasma levels of Antithrombin-III (AT-III) and plasminogen (Plg) were measured within one week stroke patient and with 27 non-stroke patient as controls. The results showed: the plasma AT-III level was of no significant difference between the patients with hemorrhagic or ischemic cerebral vascular disease group and control group; the plasma plg level was a significant decrease in ischemic cerebral vascular disease groups (cerebral infarction. TIA), and it was of significant difference between the cerebral infarction group, or the TIA group and those of the control group (P less than 0.001 and P less than 0.01) respectively. In view of these results suggest that measuring of Plasma Plg level is a valuable unspecific assays indicator for ischemic cerebral vascular diseases. Finally, the relationship between high coagulation and acute cerebral vascular disease was discussed.
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PMID:[Observation of plasma levels of antithrombin-III and plasminogen in acute cerebrovascular disease]. 262 May 88

PARD is a prospective study sponsored by the German research council with the aim to establish whether spontaneously enhanced platelet aggregation or changes of other hemostatic parameters are risk factors for new vascular occlusion in diabetic patients. Hemostatic parameters have been measured in diabetic patients at 3 month-intervals (363 patients aged 45-65 at recruitment). Of the 232 men, 53 were on diet, 104 on oral antidiabetic drugs and 75 on insulin. Of 131 women 16 were on diet, 46 on oral antidiabetic drugs and 69 on insulin. Baseline data and preliminary results obtained between May 1977 and December 31, 1983 are presented. 22 patients have died. 17 diet from cardiovascular disease, 3 from pancreatic cancer and 2 from other causes. 51 patients suffered a myocardial infarction, stroke or peripheral arterial occlusions. The mean levels of spontaneous aggregation (angle alpha-PAT III), F VIIIC, F VIII R:AG, fibrinogen, antithrombin III and plasminogen were higher in men who died or suffered cardiovascular occlusions than in those without these events. In women this difference is less pronounced or absent. In women the mean values of several hemostatic parameters at baseline were higher than in men and the incidence of cardiovascular occlusions was lower. The interim results lead to the hypothesis that spontaneous aggregation, high levels of F VIIIC, F VIII R:AG and to some extent also high levels of fibrinogen, antithrombin III and plasminogen may be indicators of progressive vascular disease and could be useful as predictors of vascular occlusions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:PARD: platelet aggregation as a risk factor in diabetics: results of a prospective study. 293 12


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