RESUMEN
The pro-inflammatory cytokine, interleukin-1 beta, induces the mRNA for prostaglandin endoperoxide synthase II gene in renal mesangial cells. This inductive effect is selective for prostaglandin endoperoxide synthase II and not prostaglandin endoperoxide synthase I. In the present experiments IL-1 beta increased COX II mRNA, and this was inhibited by genistein and herbimycin A, both inhibitors of protein tyrosine kinases. The dose dependent effect of genistein on inhibition of mRNA for COX II correlated with the inhibition of the release of PGE2 into the media. Induction of COX II by interleukin-1 beta was mimicked by incubating the cells in the presence of a protein tyrosine phosphatase inhibitor, vanadate. These experiments also illustrate selective induction of COX II mRNA without induction of COX I mRNA. Western analysis utilizing antiphosphotyrosine antibodies demonstrated in whole lysates of mesangial cells treated with interleukin-1 beta that the transient phosphorylation of several proteins occurred. Interleukin-1 beta induced the transient phosphorylation of a protein of about 39/40 kD. Similarly, vanadate also produced a rapid and transient phosphorylation of a protein of about 39/40 kD in addition to other proteins. Immunoprecipitation of mesangial cell lysates with agarose conjugated antiphosphotyrosine antibody and Western analysis of precipitated proteins with anti-ERK2 antibody demonstrate that the 39/40 kD protein phosphorylated on tyrosine is ERK2 and suggests participation of one of the MAP kinase family of extracellular receptor kinases in IL-1 beta stimulated induction of the COX II gene.
Asunto(s)
Mesangio Glomerular/efectos de los fármacos , Interleucina-1/farmacología , Prostaglandina-Endoperóxido Sintasas/efectos de los fármacos , ARN Mensajero/metabolismo , Tirosina/metabolismo , Animales , Benzoquinonas , Células Cultivadas , Dinoprostona/metabolismo , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Genisteína , Mesangio Glomerular/enzimología , Isoflavonas/farmacología , Lactamas Macrocíclicas , Masculino , Fosforilación , Prostaglandina-Endoperóxido Sintasas/genética , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Quinonas/farmacología , ARN Mensajero/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Rifabutina/análogos & derivados , Vanadatos/farmacologíaRESUMEN
OBJECTIVES: To evaluate the results of intraoperative duplex scans during carotid endarterectomy. DESIGN: Retrospective case review. MATERIALS: One-hundred consecutive intraoperative carotid duplex scans performed during carotid endarterectomy between July 1993 and December 1995 at a university teaching hospital. METHODS: Abnormalities of the B-mode image and/or the Doppler flow analysis were classified. The result of intraoperative carotid duplex scans (ICDS) were related to the events of the intraoperative course, perioperative neurologic morbidity and mortality, and to residual carotid stenosis. RESULTS: Abnormalities of the ICDS were demonstrated in 13 cases (13%). Abnormalities were classified into four types: I, internal carotid artery spasm (n = 9); II, high distal resistance flow (n = 2); III, high grade residual stenosis (n = 1); IV, intraluminal thrombosis (n = 1). Immediate intraoperative exploration and revision of the endarterectomy was performed based on the ICDS in two cases (type III and IV) and the findings of ICDS were confirmed. The other 11 cases with abnormal ICDS (types I, II) were not revised and duplex scans done 1 month postoperatively (available in 10 cases) showed normal carotid artery flow. Intraoperative angiography was performed selectively in five cases and confirmed the results of ICDS. Reversible abnormalities of the ICDS were not associated wit perioperative morbidity or residual carotid stenosis. CONCLUSIONS: Intraoperative carotid duplex scanning can be used to assess the immediate technical adequacy of carotid endarterectomy. B-mode image and Doppler flow abnormalities which are reversible can be distinguished from those which require immediate revision.
Asunto(s)
Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/cirugía , Endarterectomía Carotidea , Ultrasonografía Doppler Dúplex , Anciano , Arterias Carótidas/diagnóstico por imagen , Estenosis Carotídea/diagnóstico por imagen , Estenosis Carotídea/cirugía , Trastornos Cerebrovasculares/prevención & control , Femenino , Humanos , Cuidados Intraoperatorios/métodos , Masculino , Reoperación , Estudios Retrospectivos , Ultrasonografía Doppler Dúplex/estadística & datos numéricosRESUMEN
The inflammatory cytokine interleukin 1 beta (IL-1 beta) induces both cyclooxygenase (COX) and nitric oxide synthase (NOS) with increases in the release of prostaglandin (PG) and nitric oxide (NO) by mesangial cells. Recently, activation of the COX enzyme by NO has been described. However, the effects of COX products (PGs) on the NO pathway have not been fully clarified. Thus we determined the effect of COX inhibition and exogenous PGs on NO production and NOS induction in rat mesangial cells. A COX inhibitor, indomethacin, enhanced IL-1 beta-induced steady-state level of the inducible NOS (iNOS) mRNA and nitrite production. The effect of indomethacin was dose dependently reversed by the replacement of endogenous PGE2 with exogenous PGE2, which is the predominant product of the COX pathway in rat mesangial cells. In contrast to PGE2, a stable analog of PGI2, carba prostacyclin, enhanced IL-1 beta-induced iNOS mRNA levels and nitrite production. Forskolin, an activator of the adenylate cyclase, mimicked the effect of carba prostacyclin but not PGE2. These data suggest that (i) endogenous PGE2 downregulates iNOS induction, (ii) this inhibitory effect of PGE2 on iNOS induction is not mediated by activation of adenylate cyclase, and (iii) exogenous PGI2 stimulates COX induction possibly by activation of adenylate cyclase.