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

Since, their introduction, COX (cyclooxygenase enzyme)-2 specific inhibitors have become a rapidly growing segment of the prescription drug market. Researchers have recently focused on the potentially lethal side effects associated with their. FDA has banned the use of nimesulide (hepatotoxic) in pediatric patients and rofecoxib (cardiovascular complications) in both adults and children. COX-2 inhibitors may decrease vascular prostacyclin production and may tip the balance in favour of prothrombotic eicosanoids (thromboxane A2) and lead to increased cardiovascular thrombotic events. COX-2 inhibitors can also result into increase blood pressure, macular eruptions, urticaria, pseudoporphyria, erythema multiforme, oedema, worsening of heart failure, fatal allergic vasculitis and aggravation of doxorubicin-mediated cardiac injury. The COX-2 enzyme is also involved in the development of many organ systems, and its inhibition may lead to various congenital defects in neonates. It has been reported that COX-2 inhibitors also interfere with implantation, hence their use should be avoided in sexually active women at risk of pregnancy. However, presently the choice of COX-2 selective inhibitors for a particular patient should be based upon their relative efficacy, toxicity, concomitant drug use, concurrent disease states, hepatic and renal function and relative cost.
 ...
PMID:COX-2 selective nonsteroidal anti-inflammatory drugs: current status. 1592 4

Rickettsiae, a diverse group of obligately intracellular gram-negative bacteria, include etiologic agents of the spotted fever and typhus groups of diseases. Rocky Mountain spotted fever and boutonneuse fever, due to Rickettsia rickettsii and R. conorii, respectively, are characterized by widespread infection of the vascular endothelium, microvascular injury, and vasculitis. Cultured human endothelial cells (EC) are highly susceptible to infection and respond by altering the expression of adhesion molecules, regulatory cytokines, and the antioxidant enzyme heme oxygenase (HO). In the vasculature, HO regulates the cyclooxygenase (COX) enzymes, among which the inducible isozyme COX-2 facilitates the synthesis of prostaglandins (PGs). Using in vitro and ex vivo models of infection, we demonstrate here that R. rickettsii infection of human EC causes robust induction of COX-2 mRNA and protein expression but has no apparent effect on the constitutive COX-1 isoform. Cells infected with viable rickettsiae consistently displayed significantly increased secretion of 6-keto-PGF(1alpha) and PGE(2). R. rickettsii-induced COX-2 was sensitive to inhibitors of de novo transcription and the pyridinylimidazole-based compound SB 203580, suggesting that this transcriptional host cell response involves signaling through p38 mitogen-activated protein kinase. PG production by infected cells was abrogated by NS 398 (a selective COX-2 inhibitor) and indomethacin (a pan-COX inhibitor). Immunohistochemical staining of sections of infected umbilical cords and corresponding uninfected controls revealed comparatively more intense and abundant staining for COX-2 in infected endothelia. Induction of the endothelial COX-2 system and the resultant enhanced release of vasoactive PGs may contribute to the regulation of inflammatory responses and vascular permeability changes during spotted fever rickettsioses.
 ...
PMID:Infection of human endothelial cells with spotted Fever group rickettsiae stimulates cyclooxygenase 2 expression and release of vasoactive prostaglandins. 1692 98