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)

Use of the immunosuppressant drug cyclosporine A (CSA) has resulted in improved renal graft survival. However, an increased incidence of arterial and venous thrombotic diseases, hemolytic-uremic type syndrome, and findings resembling vasculitis in the kidneys of patients with CSA nephrotoxicity and accelerated atherogenesis have been reported. These disorders may be related to CSA-induced abnormalities in platelet function. We report here that CSA causes increased ADP-stimulated aggregation in isolated platelet suspensions indicating that CSA has a direct effect on platelet function, independent of CSA interactions with plasma factors. Maximal hyperaggregability of ADP-stimulated platelets occurred following a 1 h preincubation period with CSA. Hyperaggregability of platelets due to the presence of CSA was dose-dependent and approached plateau between 200-500 ng/ml CSA. We determined that CSA exerted its effects through a signal transduction pathway involving the phosphorylation of two intracellular proteins, a 40 kD substrate of PKC (p47) and the 20 kD light chain of myosin (p20), a substrate of calcium/calmodulin dependent kinase. Preincubation with CSA resulted in a 200% increase in the phosphorylation of these proteins in platelets stimulated with ADP. We conclude that CSA enhances ADP-induced platelet aggregation and secretion, in part, by potentiating the phosphorylative response of specific intracellular proteins to stimulation by agonists. This process may be responsible for the increased thrombosis and atherogenesis observed in CSA-treated patients.
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PMID:Cyclosporine A enhances agonist-induced aggregation of human platelets by stimulating protein phosphorylation. 829 40

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

Severe forms of bronchial asthma (BA) are encountered now more and more frequently. Therefore, number of patients treated by course steroids in BA exacerbation and patients on continuous basic therapy with systemic glucocorticosteroids(GCS) grows. Pathogenesis of steroid vasculitis (SV) is though to be related with GCS effect on the skin, hemostasis and directly on the vessels. We studied platelet function and antithrombogenic activity of vascular wall (AAVW) in patients with steroid-dependent BA (SDBA) in development of cutaneous hemorrhagic syndrome (CHS). We examined 30 patients with SDBA and cutaneous vasculitis and 19 SDBA patients free of this vasculitis. A control group consisted of 29 healthy volunteers. Assessment of ADP-induced platelet aggregation, AAVW demonstrates enhanced functional activity of platelets and definite impairment of antithrombogenic endothelial activity in patients with SDBA and CHS. We came to the conclusion that AAVW affection is involved in pathogenesis of SV in SDBA patients.
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PMID:[Steroidal vasculitis in patients with bronchial asthma: specific features of platelet function and antithrombogenic vascular activity]. 1268 31

Haemophilus somnus is a bacterial pathogen that causes respiratory disease and vasculitis in cattle. Thrombotic meningoencephalitis (TME) and other severe forms of H. somnus-mediated vascular disease are characterized histopathologically by vasculitis, thrombosis, and infiltration of polymorphonuclear cells. It has been reported previously that activated human platelets express CD40L, FasL and P-selectin (CD62P). We hypothesized that if these surface markers are up-regulated on bovine platelets after in vitro exposure to H. somnus and its lipooligosaccharide (LOS), they might contribute to endothelial cell damage. Using flow cytometry, we demonstrated low baseline expression of these molecules by bovine platelets and increased expression following in vitro stimulation with ADP, H. somnus or H. somnus LOS. H. somnus stimulated platelets were capable of causing apoptosis in endothelial cells as measured by Hoechst-33342 staining and caspase-3 activity. If these events occur in vivo, they might promote vascular damage and endothelial cell apoptosis, leading to the development of vasculitis and thrombosis that characterize bovine H. somnus infection.
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PMID:Bovine platelets activated by Haemophilus somnus and its LOS induce apoptosis in bovine endothelial cells. 1565 92

Cyclosporine A (CyA) is known to be associated with an increased risk of thrombotic complications, whereas FK 506 therapy is believed to cause vasculitis. The aim of the study was to evaluate platelet aggregation in platelet rich plasma (PRP) and in whole blood and ATP release in healthy volunteers. CyA added in different concentrations resulted in a dose-dependent enhancement in platelet response to different agonists in PRP, whereas FK 506 did not influence platelet aggregation when added at a concentration of 2 ng/ml. Preincubation with FK 506 at concentrations of 15 and 50 ng/ml significantly inhibited platelet response to serotonin and epinephrine. Preincubation with both CyA and FK 506 did not affect platelet aggregation either in PRP or in whole blood. CyA at every concentration studied resulted in dose-dependent enhancement in ADP-induced platelet aggregation in whole blood, whereas platelet responses to other agonists were found to be increased only with the highest concentration of CyA together with ATP release. FK 506 (50 ng/ml) resulted in a significant decline in platelet aggregation, whereas lower concentrations did not affect platelet aggregatory responses. Platelet hyperreactivity in response to CyA may contribute, at least in part, to the increased incidence of thrombosis events. Platelet effects of FK 506 in vivo are not yet known, whereas in vitro this drug seems to inhibit aggregation of normal human platelets.
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PMID:Original Article: Cyclosporine a and FK 506 Affect Platelet Functions in Vitro. 2104 66