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)

Production of the third and fourth components of complement (C3, C4) by smooth muscle cells was investigated by using normal human aortic smooth muscle cells (AoSMC), human smooth muscle cell line (G402) and vascular smooth muscle cells obtained from human umbilical cord vein (UVSMC). AoSMC spontaneously produced both C3 and C4 at 15 ng/10(6) cells/72 hr and 22 ng/10(6) cells/72 hr, respectively, and both were enhanced by interferon-gamma (IFN-gamma). Although phorbol 12-myristate 13-acetate (PMA) and tumour necrosis factor-alpha (TNF-alpha) enhanced C3 production, C4 production was reduced by these agents. On the other hand, G402 produced C4 but not C3 in a dose-dependent manner when cultured with IFN-gamma. UVSMC produced only a small amount of C3 and C4 compared with AoSMC or G402. C3 and C4 produced by AoSMC were confirmed to be identical with their human serum counterparts as determined by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and measurement of haemolytic activity. Northern blotting analysis showed that the expression of mRNA of C3 and C4 was enhanced by TNF-alpha and IFN-gamma, respectively, in AoSMC. Our findings suggest the importance of smooth muscle cells as a source of components of complement in vascular diseases including vasculitis.
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PMID:Production of the third and fourth component of complement (C3, C4) by smooth muscle cells. 894 12

Because polymorphonuclear (PMN) neutrophils are major effector cells in vasculitides, we assessed whether disease-modifying antirheumatic drugs impaired the ability of human PMNs to lyse human umbilical vein endothelial cells (HUVECs) in vitro. HUVECs were grown to confluence and labeled with chromium 51. PMNs, stimuli, and antirheumatic drugs were added stepwise, and the release of 51Cr was subsequently assessed. Lipoxin A4 (LXA4) and the oligopeptide fMLP, activating PMNs by surface receptors, conferred highly significant cytolysis that was dose-dependently reduced when auranofin, gold sodium aurothiomalate (GSTM), and sulfasalazine and its metabolites sulfapyridine and 5-ASA were added to the assay system. This protection remained, but with stimulus- and drug-specific variations, when either PMNs or HUVECs alone were treated with drugs before washings and PMN activation. In contrast, methotrexate did not protect HUVECs. Cytotoxicity conferred by the ionophore A23187 was inhibited by auranofin and GSTM only. Likewise, when HUVEC cytolysis was induced by two major cytotoxic mechanisms of PMNs, exogenous H2O2, or PMN lysates, auranofin and GSTM hampered lysis significantly. Thus in this in vitro model of vasculitis, auranofin, GSTM, sulfasalazine, sulfapyridine, and 5-ASA--but not methotrexate--dose-dependently reduced the PMN-dependent endothelial cell damage by effects on the PMNs as well as effects on the HUVECs.
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PMID:Inhibition of neutrophil-dependent cytotoxicity for human endothelial cells by antirheumatic drugs. 896 Jun 38

While the relative incidence of serious nephrotoxicities in the population consuming nonsteroidal anti-inflammatory drugs (NSAIDs) is very low, the frequency of adverse events in patients at risk has considerably increased due to the rising popularity of the use of the drugs in recent years. Under normal conditions, NSAIDs have relatively little effect on the kidney because of low renal production of prostaglandins. However, in the presence of renal hypoperfusion in which local synthesis of vasodilator prostaglandins is increased to protect the glomerular hemodynamics and to maintain appropriate renal tubular transport of fluid and electrolytes, inhibition of prostaglandin synthesis by NSAIDs can lead to vasoconstrictive acute renal failure as well as fluid and electrolyte disorders such as sodium retention and resistance to diuretics, hyponatremia and hyperkalemia. Conditions that increase the risk for NSAID-induced nephrotoxicities include volume depletion from diuretics and other causes, edematous states such as congestive heart failure and cirrhosis of the liver, old age and underlying renal disease, especially in the presence of renal functional impairment. In addition, renal parenchymal diseases may develop in susceptible patients taking NSAIDs. These include acute tubulointerstitial nephritis, frequently associated with nephrotic syndrome, and chronic progressive renal disease, with or without renal papillary necrosis. Rare cases of vasculitis and glomerulonephritis have also been reported. Finally, NSAIDs may aggravate hypertension by interacting with antihypertensive drugs, especially with diuretics and beta-blockers. Withdrawal of NSAIDs in patients at risk can frequently reverse or improve the nephrotoxicities. It is recommended that physicians be aware of the clinical settings that increase the risk for NSAID-induced nephrotoxicities and take preventive or therapeutic measures accordingly.
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PMID:Nephrotoxicities of nonsteroidal anti-inflammatory drugs. 908 Jul 53

Cause of mortality was studied in waterfowl in hypersaline playa lakes of southeast New Mexico during spring and fall migration. Mortality was not common in wild ducks resting on the playas during good weather. However, when birds remained on the lakes for prolonged periods of time, such as during experimental trials and stormy weather, a heavy layer of salt precipitated on their feathers. Sodium toxicity was the cause of death for all experimental mallards housed on playa water and for 50% of the wild waterfowl found moribund or dead during the spring of 1995. Gross lesions included heavy salt precipitation on the feathers, ocular lens opacities, deeply congested brains, and dilated, thin-walled, fluid-filled cloacae. Microscopic lesions in the more severely affected birds included liquefaction of ocular lens cortex with lens fiber swelling and multifocal to diffuse ulcerative conjunctivitis with severe granulocytic inflammation, edema, and granulocytic vasculitis resulting in thrombosis. Inflammation similar to that seen in the conjunctiva occasionally involved the mucosa of the mouth, pharynx, nasal turbinates, cloaca, and bursa. Transcorneal movement of water in response to the hypersaline conditions on the playa lakes or direct contact with salt crystals could induce anterior segment dehydration of the aqueous humor and increased osmotic pressure on the lens, leading to cataract formation.
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PMID:Sodium toxicity and pathology associated with exposure of waterfowl to hypersaline playa lakes of southeast New Mexico. 924 66

An apparently novel adenovirus was associated with an epizootic of hemorrhagic disease that is believed to have killed thousands of mule deer (Odocoileus hemionus) in California (USA) during 1993-1994. A systemic vasculitis with pulmonary edema and hemorrhagic enteropathy or a localized vasculitis associated with necrotizing stomatitis/pharyngitis/glossitis or osteomyelitis of the jaw were common necropsy findings in animals that died during this epizootic. Six black-tailed yearling deer (O. hemionus columbianus) were inoculated with purified adenovirus isolated from a black-tailed fawn that died of acute adenovirus hemorrhagic disease during the epizootic. Three of six inoculated deer also received intramuscular injections of dexamethasone sodium phosphate every 3 days during the study. Eight days post-inoculation, one deer (without dexamethasone) developed bloody diarrhea and died. Necropsy and histopathologic findings were identical to lesions in free-ranging animals that died of the natural disease. Hemorrhagic enteropathy and pulmonary edema were the significant necropsy findings and there was microscopic vascular damage and endothelial intranuclear inclusion bodies in the vessels of the intestines and lungs. Adenovirus was identified in necrotic endothelial cells in the lungs by fluorescent antibody staining, immunohistochemistry and by transmission electron microscopy. Adenovirus was reisolated from tissues of the animal that died of experimental adenovirus hemorrhagic disease. Similar gross and microscopic lesions were absent in four of six adenovirus-inoculated deer and in the negative control animal which were necropsied at variable intervals during the 14 wk study. One deer was inoculated with purified adenovirus a second time, 12 wk after the first inoculation. Fifteen days after the second inoculation, this deer developed severe ulceration of the tongue, pharynx and rumen and necrotizing osteomyelitis of the mandible which was associated with vasculitis and thrombosis of adjacent large vessels and endothelial intranuclear inclusions. Transmission electron microscopy demonstrated adenovirus within the nuclei of vascular cells and immunohistochemistry demonstrated adenovirus antigen within tonsilar epithelium and in rare vessels.
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PMID:Experimental adenovirus hemorrhagic disease in yearling black-tailed deer. 939 65

Adverse skin reactions to low molecular weight heparins (LMWH) are rare even though their true incidence is probably underestimated because of under-reporting. These reactions may occur as an urticarial rash, presumably due to local histamine release or have the features of a classic type I immediate hypersensitivity reaction. They can also present as skin necrosis often due to vasculitis (type III Arthus reaction) or heparin-induced thrombocytopenia. Erythematous, well circumscribed lesions without necrosis are usually secondary to a delayed type IV hypersensitivity reaction. Although most LMWH-induced skin lesions are benign, treatment should be discontinued. In type I reactions or in the presence of skin necrosis with or without heparin-induced thrombocytopenia, the LMWH should be replaced by an alternative medication such as danaparoid sodium or hirudin. Platelet counts should be monitored to diagnose heparin-induced thrombocytopenia. In a type IV delayed hypersensitivity reaction, in the absence of severe, extensive, life-threatening mucocutaneous manifestations, a first-line pragmatic approach consists, in our view, of replacing the particular LMWH with another one. If the skin symptoms do not improve, cutaneous tests may help detect the presence of a cross-reactivity between the available preparations of LMWHs and danaparoid sodium. In the presence of a negative subcutaneous provocation test, the compound can be used with little risk. If all types of LMWH and danaparoid sodium are positive in skin testing, mechanical prevention or oral anticoagulants should be used, and intravenous injections of any kind of heparin should be avoided because of the potential risk of anaphylactic shock. Alternatively, hirudin might be administered but experience with this compound is still very limited. Prevention is only possible in type IV hypersensitivity skin reactions, by avoiding long term LMWH therapy, particularly in middle-aged, obese women and during pregnancy. In these patients, oral anticoagulation should be preferred, whenever possible. In conclusion, though rare, skin reactions to LMWH may have important consequences which can be reduced by rapid diagnosis and appropriate management.
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PMID:Adverse skin reactions to low molecular weight heparins: frequency, management and prevention. 1039 68

Anti-neutrophil cytoplasmic antibodies (ANCA) are a family of autoantibodies which react with components of phagocytic cells, and are associated with vasculitis and other idiopathic inflammatory disorders. However, the antigenic targets of many of these autoantibodies have not been defined yet. In this study, sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and isoelectric focusing (IEF) were evaluated for characterising the antigenic specificity of unidentified ANCA. The uncharacterised sera included those from patients with ulcerative colitis (n = 21), Crohn's disease (n = 5), cystic fibrosis (n = 16) and sarcoidosis (n = 2). In addition, sera from patients with antibodies to the phagocytic enzymes proteinase 3 (PR3) (n = 11) and myeloperoxidase (MPO) (n = 5) were also included. The sub-cellular localisation of antigens was determined by testing sera against crude neutrophil extract and sub-cellular fractions consisting of azurophilic granules, specific granules and cytosolic, fractions using enzyme-linked immunosorbent assays (ELISAs). All sera reacted with the crude and azurophilic granule extracts. The native system of IEF followed by capillary immunoblotting successfully detected anti-PR3 and anti-MPO in azurophilic granule extracts. In contrast, SDS-PAGE Western blotting failed to detect any reactivity, either to PR3 or MPO, in the crude extract or azurophilic granule extract. However, the antibody specificity of patient sera with uncharacterised autoantibodies could not be detected by IEF/capillary immunoblotting or SDS-PAGE. This study showed that the sub-cellular azurophilic granules are the antigenic target of a variety of uncharacterised ANCA. It also showed that IEF characterised both anti-PR3 and anti-MPO but failed to detect other forms of ANCA. In contrast, the majority of common ANCA were not detected by SDS-PAGE.
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PMID:Characterisation of anti-neutrophil cytoplasmic antibody target antigens using electrophoresis and western blotting techniques. 1043 39

We have previously shown that the gold-containing disease-modifying anti-rheumatic drugs, auranofin (AF) and gold sodium aurothiomalate (GSTM) reduce human umbilical vein endothelial cell (HUVEC) adhesion molecule expression and neutrophil (PMN) adherence. AF diminishes E-selectin and intercellular adhesion molecule-1 (ICAM-1) on cytokine-activated HUVEC, while GSTM decreases only E-selectin. Since tight adhesion is critical for PMN to damage EC, we tested whether these drugs modulated human PMN-mediated injury to TNF-alpha-activated HUVEC in vitro (as measured by 51Cr release). Here we show that TNF-alpha caused a prominent PMN-mediated cytotoxicity that was dose-dependently reduced when AF and GSTM were added to the assay system. We also found that a potent inhibitor of NF-kappaB, pyrrolidine dithiocarbamate (PDTC) in a dose-dependent manner impaired TNF-alpha-induced cytotoxicity, indicating a role of NF-kappaB activation in cytokine-induced endothelial injury. To examine the effects of AF and GSTM on TNF-alpha-induced NF-kappaB activation this was measured in HUVEC nuclear extracts by an electrophoretic mobility shift assay. AF, but not GSTM, decreased TNF-alpha-induced NF-kappaB activation in HUVEC. Thus, in this in vitro model of vasculitis, AF and GSTM dose dependently reduced TNF-alpha-mediated neutrophil-dependent cytotoxicity for HUVEC, and AF, but not GSTM, inhibited NF-kappaB mobilization, thereby providing possible mechanisms for effects of AF and GSTM.
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PMID:Effects of anti-rheumatic gold salts on NF-kappa B mobilization and tumour necrosis factor-alpha (TNF-alpha)-induced neutrophil-dependent cytotoxicity for human endothelial cells. 1075 67

Acute renal insufficiency (ARI) complicated the course of the underlying process, including primary and secondary glomerulonephritis, interstitial nephritis, pyelonephritis, dysmetabolic nephropathies, urolithiasis, tubulopathies, renal congenitae defects and injuries in 136 of 1695 children with nephrological diseases hospitalized at Republican Pediatric Renal Center during the last decade. In 69.1% cases ARI developed by the renal type, in 23.5% cases was caused by prerenal factors, and rarely (in 7.4% cases) by postrenal factors. Renal ARI in children was caused by 5 causes, including glomerulonephritis (47%), acute tubular necrosis (19%), interstitial nephritis (14%), vascular disorders (11%) resultant from vasculitis, renal vein thrombosis, and acute crystalluria (9%) which developed in the presence of grave dysmetabolic nephropathy. Among three clinical variants of ARI the most severe was observed in renal ARI leading to grave endogenous intoxication and pronounced decompensation of renal function. More benign course of renal ARI caused by acute tubular necrosis or acute crystalluria differed significantly from prerenal ARI by a more pronounced endogenous intoxication, increased fractionated sodium excretion, and renal insufficiency index higher than 1.
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PMID:[Diagnosis of acute renal failure in pediatric nephrology]. 1133 30

Examinations of 407 patients with angiological disorders of the fundus oculi (diabetic retinopathy, retinal vein thrombosis, central chorioretinal dystrophy, retinal angiitis) revealed relapsing hemorrhagic syndrome in 40% (170) patients. No thrombocytopenia was revealed in any of the patients, which suggests qualitative impairment of platelets in such patients. Evaluation of the platelet aggregation coefficient (PAC) using thrombin aggregation inducers and adenosine diphosphate disodium revealed a statistically significant decrease of PAC for one or both aggregants in all 170 patients with the hemorrhagic syndrome, which indicated platelet dysfunction. A course of intramuscular injections of 1% adenosine triphosphate sodium normalized platelet function and stimulated resorption of hemorrhages.
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PMID:[Thrombocytopathies and their role in the development of hemorrhagic syndrome in vascular diseases of the fundus oculi]. 1133 33


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