Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042384 (vasculitis)
 20,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Livedoid vasculitis, a hyalinizing vasculopathy, is characterized by extensive formation of microthrombi and deposition of fibrin in the middermal vessels, which result in epidermal infarction, ulceration, and formation of stellate scars. In a prospective study of nonhealing ulcers in patients with livedoid vasculitis, we found a high incidence of anticardiolipin antibodies, lupus anticoagulants, increased levels of plasminogen activator inhibitor, and low levels of endogenous tissue plasminogen activator (t-PA) activity. This procoagulant tendency and decreased fibrinolysis may provide an explanation for the occlusive vasculopathy often noted in biopsy specimens from these patients. On the basis of these findings, we proposed that fibrinolysis with recombinant t-PA would lyse microvascular thrombi, restore circulation, and promote wound healing. In six patients who had nonhealing ulcers caused by livedoid vasculitis and in whom numerous conventional therapies had failed, low-dose t-PA (10 mg) was administered intravenously during a 4-hour period daily for 14 days. Five of the six patients had dramatic improvement; almost complete healing of the ulcers occurred during hospitalization, and tissue oxygenation, as measured by transcutaneous oximetry, increased. The one treatment failure was due to rethrombosis of the microvasculature; this patient was subsequently re-treated but with concurrent anticoagulation, and her leg ulcers healed. We conclude that daily administration of a low dose of t-PA is safe and effective treatment for nonhealing ulcers due to occlusive vasculopathy.
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PMID:Tissue plasminogen activator for treatment of livedoid vasculitis. 143 47

Essential mixed cryoglobulinemia (EMC) is a rheumatic disorder characterized by widespread vasculitis. To better define the nature of the vasculitic process and to possibly outline assessment methods reliable for using in a clinical context, we studied plasma levels of three endothelial related peptides: fibronectin (FN), von Willebrand factor (vWF) and tissue plasminogen activator (t-PA), and those of thrombin-antithrombin III complexes (TAT) as markers of activation of the coagulation in 21 patients and in 16 controls. In EMC we found a picture consisting of reduced FN and increased vWF, t-PA, and TAT levels, suggesting a condition of endothelial cell damage with thrombin formation in vivo. Since we previously demonstrated the presence of chronic disseminated intravascular coagulation in these patients, we may assume that endothelial cells stressed by cryoprecipitation or stimulated by soluble mediators may be actively involved in the vasculitic process and possibly express procoagulant properties. This is a good example of the complex interplay existing between autoimmunity and coagulation mechanisms. We also suggest that FN, vWF, t-PA and TAT should be considered as additional clinical parameters when evaluating patients with EMC.
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PMID:Clinical significance of endothelial damage markers in essential mixed cryoglobulinemia. 195 Mar 76

Twenty outpatients presenting with Raynaud's phenomenon secondary to clinical or preclinical inflammation of connective tissue were treated orally with defibrotide 400 mg three times daily or a matching placebo in a randomized double-blind study. The test product defibrotide (a polydeoxyribonucleic acid compound of animal origin with demonstrated profibrinolytic activity when administered parenterally) was administered orally for 3 weeks in order to explore its effects on the parameters of extrinsic fibrinolysis before and after venous stasis. The antigen of t-PA and its inhibitor PAI, free and total, and the biologic activity of PAI were assayed in basal conditions and after treatment. Although a marked increase of t-PA was seen with the active treatment, PAI activity was significantly reduced by defibrotide. Immunoreactive PAI was not significantly modified by treatment, even though it dropped considerably after venous stasis in the defibrotide group. Thus, the disturbance of endothelial function that seems to occur in vasculitis and in Raynaud's phenomenon secondary to inflammation of connective tissue (or so suspected to be) would constitute the basis of a disturbance of fibrinolysis, which oral defibrotide seems able to correct. Further studies are warranted to define the clinical effectiveness of this treatment in patients with Raynaud's phenomenon.
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PMID:Deficient fibrinolytic response in patients with Raynaud's phenomenon and its correction with defibrotide. 206 63

The fibrinolytic system in a group of 23 patients with vasculitis and 10 patients with the cutaneous vasculitis atrophie blanche were studied. These patients were found to have markedly suppressed release of vascular tissue plasminogen activator (t-PA) stores whether the disease was active or in remission. The control group had releasable t-PA levels of 0.70 +/- 0.10 IU/ml of plasma. Levels of releasable t-PA in the patient population were 0.09 +/- 0.03 IU/ml for those with active vasculitis (p less than 0.0001 compared with the control group by the Student t test), 0.23 +/- 0.12 IU/ml for those with inactive vasculitis (p less than 0.001), and 0.03 +/- 0.01 IU/ml for those with atrophie blanche (p less than 0.0001). It is concluded that there is a generalized defect in plasminogen activator in a variety of vasculitides. Such a defect may contribute to the pathogenesis of lesions as well as the thromboembolic disease that may be observed in these patients.
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PMID:Defective release of tissue plasminogen activator in systemic and cutaneous vasculitis. 310 39

Plasma fibrinolytic activity was measured in 34 patients with systemic lupus erythematosus (SLE) and 12 normal subjects. Patients with SLE showed a significantly reduced resting level of plasma tissue plasminogen activator (t-PA) compared to normal. The reduction in t-PA was demonstrated both by a functional assay (fibrin-plate lysis, FP) and an immunochemical assay (ELISA). Measurement of the fibrinolytic response following venous occlusion allowed division of the patients into two groups. In the first (24 patients), there was a normal increase in t-PA response, demonstrated both by the functional and immunochemical assays. In the second (10 patients), there was a significantly reduced plasma t-PA response measured by FP. Seven of the patients in this second group, which included four patients with histological evidence of vasculitis, showed a similar failure of t-PA response (ELISA) after venous occlusion. These results suggest that their impaired fibrinolytic response may be related to defective t-PA release secondary to endothelial cell damage. The remaining three patients in the latter group had a normal t-PA (ELISA) response despite a reduced FP response, suggesting the presence of an inhibitor.
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PMID:Abnormal fibrinolytic activity in systemic lupus erythematosus and possible mechanisms. 314 7

The activity of plasminogen activator has been measured in tissue sections with the aid of a modified Todd technique. Frozen skin biopsies were sectioned and the tissue covered with fibrin-plasminogen film. After incubation at 37 degrees C fibrinolysis was studied for a period of 30 min and was graded into six exponentially increasing steps. During this period, grades were linear with the llogarithm of time of incubation. The rate of fibrinolysis is a measure of the activity of the plasminogen activator and is expressed by the slope of the linear regression of grades versus the ogarithm of time; the value of the slope is proportional to the common logarithm of the activity of the plasminogen activator present in the section. Using urokinase as a specific plasminogen activator, the same linear expression was shown with time, indicating the validity of our grading and experimental system. Eleven healthy subjects served as controls to 6 patients with leukocytoclastic vasculitis and 4 patients with erysipelas and 4 with necrotizing fascilitis. The controls showed values similar to the non-involved skin in the patients. The activity was higher in the arm than in the thigh sites. The activity in the thighs was lower in women than in men. A decrease in the plasminogen activator activity was found in the three disorders.
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PMID:An improved quantitative method for the study of fibrinolysis in the skin as exemplified in patients with leukocytoclastic vasculitis and erysipelas. 616 72

A tissue plasminogen activator was extracted from skin lesions with allergic vasculitis and purified by successive column chromatography on Sephadex G-200, DEAE-cellulose, Hydroxyaptite-cellulose and polyacrylamide gel electrophoresis. By these procedures, 160 micrograms of enzyme with a specific activity of 843.8 international units/mg protein was obtained from 5 g of original skin. The purified material was homogeneous as ascertained by sodium dodecyl sulfate polyacrylamide gel electrophoresis and had an apparent molecular weight of 110,000 as measured by gel filtration on Sephadex G-200. Its identity with human urokinase was investigated and was found to possess the same plasminogen activator activity as that of urokinase. It had high amindolytic activity, but only slight N-alpha-acetyl-glycyl-L-lysine methyl ester esterolytic activity. This tissue plasminogen activator was confirmed to be immunologically identical to human urokinase.
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PMID:Isolation of tissue plasminogen activator from skin lesions with allergic vasculitis. 719 68

Markers of endothelial cell activation were measured in 28 patients presenting with various forms of limited or focal type cutaneous vasculitis. Plasma levels of tissue plasminogen activator antigen (t-PA:Ag), plasminogen activator inhibitor type 1 antigen (PAI-1:Ag) and PAI-1 activity, fibrin plate, von Willebrand factor antigen (vWF:Ag), tissue factor (TF) and soluble thrombomodulin (sTM) were measured. In comparison with the control group (n = 20) there was a significant increase in t-PA:Ag, vWF:Ag and TF (P < 0.05, Mann-Whitney U-test) in the cutaneous vasculitis group. This study confirms that measurable degrees of endothelial activation occur in cutaneous vasculitis. Cutaneous vasculitis includes a diverse group of clinical conditions, which are associated with inflammatory changes in cutaneous blood vessels with local fibrin deposition. The aetiology and pathogenesis of the majority of these entities remain unknown. Causative mediators are thought to include immune complexes, anti-endothelial cell antibodies, cytotoxic lymphocytes and viruses. Histologically, immune complexes and complement are frequently detected on the vessel wall, and serologically anti-endothelial antibodies are often detected in patients with vasculitis and in systemic lupus erythematosus (SLE) which correlate with the severity of cutaneous vasculitis, arthritis and nephritis. Lymphocyte-mediated toxicity to endothelial cells has been reported in a small number of patients with giant cell arteritis and Takayasu's arteritis. The vascular endothelium plays a central part in the control of haemostasis. Under physiological conditions endothelial cells present an anticoagulant surface to blood constituents, partially due to surface expression of heparan sulphate and thrombomodulin (TM). Heparan sulphate binds antithrombin III (ATIII), thereby accelerating inactivation of intrinsic coagulation enzymes. Thrombomodulin is an endothelial cell surface glycoprotein which promotes anticoagulation by forming a complex with thrombin which then activates protein C. Activated protein C together with a cofactor, protein S, inactivates FVa and FVIIIa. von Willebrand factor (vWF) is synthesized by endothelial cells, stored in Weibel-Palade bodies and released into the circulation upon endothelial stimulation. vWF mediates the binding of platelets to the subendothelium and is the carrier molecule for FVIIIC. The endothelium controls fibrinolysis by producing t-PA and its inhibitor PAI-1. Inflammatory cytokines such as interleukin-1 (IL-1) and tumour necrosis factor (TNF) activate endothelial cells, causing a shift from an antithrombotic to prothrombotic state, including expression of tissue factor, increased synthesis of PAI-1 and decreased expression of TM. Fibrin deposition and intravascular thrombosis are seen in cutaneous vasculitis syndromes, suggesting local endothelial cell activation. The aim of this pilot study was to assess whether perturbation of the endothelium in cutaneous vasculitis could be detected in the patients' plasma samples. If so, further studies to assess any correlation in levels of these markers with disease activity might prove useful in the future.
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PMID:Endothelial cell activation in cutaneous vasculitis. 868 65

Defibrotide, a polydeoxyribonucleotide, has been found to modulate endothelial cell function, causing an increase in tissue plasminogen activator (t-PA) levels, a decrease in plasminogen activator inhibitor (PAI) levels, and an increase in prostaglandin I2 (PGI2) formation in humans. Defibrotide has no direct anticoagulant effect but has a synergistic action with heparin. A strong antithrombotic effect has been observed in animal models. Thus, defibrotide has a beneficial effect in cases of deep venous thrombosis (DVT), peripheral obliterative vascular disorder (POVD), stroke, vasculitis, and thromboembolism. Defibrotide also inhibits platelet function and activation. A significant decrease in platelet aggregate formation on the suture line in microarterial anastomosis in rats is one way defibrotide can inhibit platelet function and activation. In humans, a slight prolongation' of the lag period in collagen-induced aggregation has been observed. In addition, a slight decrease in the maximum amplitude of the secondary wave of ADP and adrenalin-induced aggregations was also found. Platelet adhesion is diminished, the platelet differential count on formvar membrane is altered, and platelet aggregate formation is significantly inhibited. With an increase in platelet cyclic AMP (cAMP) content and a decrease in malonyl dialdehyde (MDA) and thromboxane B2 (TXB2) formation, the levels of platelet secretion products such as PF-4 and beta-thromboglobulin (beta-TG) in plasma decreased progressively. It was also demonstrated that the 14C-glucose transport defect of the platelet membrane of atherosclerotic patients was partially corrected with defibrotide treatment.
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PMID:Effect of defibrotide on platelet function. 880 24

An occlusion of the central retinal artery (CRAO) leads to a unilateral acute painless loss of vision. The individual etiology remains unclear in many cases. Potential pathomechanisms are embolism, vasoobliteration and vascular compression. Emboli (calcified, thrombotic, myxomatous, bacterial or cholesterol) are of carotid or cardiac origin. Atherosclerotic plaques, giant-cell arteritis and other types of vasculitis may cause vasoobliteration. A retrobulbar mass (hematoma, neoplasms, retrobulbar injections) may lead to an optic nerve and central retinal artery compression. Funduscopic signs of CRAO are described. Late development of iris neovascularization and neovascular secondary glaucoma may occur in up to 15 percent of cases. The prognosis of CRAO has been poor. A spontaneous remission and recovery of visual function is rare. It has been shown experimentally that the retinal damage is irreversible after 100 minutes of non-perfusion. The initial treatment should include an immediate paracentesis of the anterior chamber, digital massage of the globe, and i.v. administration of 500 mg azetazolamide in order to stimulate retinal reperfusion by lowering the intraocular pressure. This procedure is recommended for the first 6 (up to 24) hours after onset of CRAO. More promising success rates have recently be reported by a selective intra-arterial fibrinolysis with Urokinase (100,000-1,000,000 IU) or recombinant plasminogen activator (rtPA). In a personal series of 18 cases, intra-arterial fibrinolysis with Urokinase was performed. A final visual acuity of 6/10 to 6/6 was achieved in 30 percent of the cases.
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PMID:[Central retinal artery occlusion--etiology, clinical picture, therapeutic possibilities]. 1121 85


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