Abstract-Prostaglandin (PG) E 2 has an established role in the regulation of vascular tone and reactivity. The present study examined the role and mechanism of microsomal PG synthase-1 (mPGES-1) in vascular response to angiotensin II (Ang II) infusion. A 7-day Ang II infusion at 0.35 mg/kg per day via osmotic minipump had no obvious effect on mean arterial blood pressure in mPGES-1 ϩ/ϩ mice but induced a marked hypertensive response in mPGES-1 Ϫ/Ϫ mice, associated with a parallel increase in urinary 8-isoprostane excretion and aortic NADPH oxidase activity and mRNA expression of p47 phox , gp91 phox , and Nox1. The hypertension in mPGES-1 Ϫ/Ϫ mice was completely prevented by Tempol treatment and was fully restored on termination of the antioxidant. Apocynin induced a similar blood pressure-lowering effect as Tempol. The Ang II infusion induced mRNA expression of mPGES-1, as well as mPGES-2 and cytosolic PGE synthase in the aortas as assessed by real-time RT-PCR. Immunohistochemistry revealed remarkably enhanced immunoreactivity of mPGES-1 mostly in vascular smooth muscle cells. In cultured vascular smooth muscle cells, Ang II exerted a direct stimulatory effect on reactive oxygen species production, NADPH oxidase activity, and expression of p47 phox , gp91 phox , and Nox1 that were all inhibited by PGE 2 . The Ϫ/Ϫ mice also exhibited enhanced renal hemodynamic response to acute Ang II infusion at 150 nmol/kg per minute via a jugular vein over a period of 40 minutes. These results suggest that mPGES-1-derived PGE 2 buffers Ang II-induced vasoconstriction via inhibition of NADPH oxidase-dependent reactive oxygen species production. Key Words: mPGES-1 Ⅲ angiotensin II Ⅲ mean arterial pressure Ⅲ oxidative stress Ⅲ NADPH oxidase P rostaglandin (PG) E 2 is a major product of arachidonic acid metabolism, being implicated in pain and inflammatory responses, as well as in the regulation of various physiological functions. 1 The biosynthesis of PGE 2 requires 3 sequential steps of the cyclooxygenase pathway: the release of arachidonic acid from membrane glycerophospholipids by phospholipase A 2 , conversion of arachidonic acid to the unstable intermediate PGH 2 by cyclooxygenase-1 or cyclooxygenase-2, and isomerization of PGH 2 to PGE 2 by PGE synthase (PGES). 2,3 To date, Ն3 major forms of PGES have been cloned and characterized: membrane-associated PGES (mPGES)-1, mPGES-2, and cytosolic PGES (cPGES). 3 Several recent studies using mPGES-1-deficient mice demonstrate a major role of mPGES-1 in pain and inflammatory responses. 4,5 The cardiovascular consequences associated with cyclooxygenase-2 inhibitors 6 -9 have stimulated the interest regarding mPGES-1 as a potential target for the next generation of anti-inflammatory drugs. 10
PAF episodes are associated with faster heart rates and last longer in women, which may reflect differing autonomic responses to AF. A slower ventricular rate during PAF in older patients probably reflects an increasing prevalence of impaired atrioventricular conduction.
An initial energy setting of > or =360 J can achieve cardioversion of AF more efficiently in patients than traditional protocols, particularly with AF of longer duration.
Abnormal repolarization is associated with arrhythmogenesis. Because of controversies in existing methodology, new computerized methods may provide more reliable tools for the noninvasive assessment of myocardial repolarization from the surface electrocardiogram (ECG). Measurement of the interval between the peak and the end of the T wave (TpTe interval) has been suggested for the detection of repolarization abnormalities, but its clinical value has not been fully studied. The intrasubject reproducibility and reliability of automatic measurements of QT, QT peak, and TpTe interval and dispersion were assessed in 70 normal subjects, 49 patients with acute myocardial infarction (5th day; MI), and 37 patients with hypertrophic cardiomyopathy (HC). Measurements were performed automatically in a set of 10 ECGs obtained from each subject using a commercial software package (Marquette Medical Systems, Milwaukee, WI, U.S.A.). Compared to normal subjects, all intervals were significantly longer in HC patients (P < 0.001 for QT and QTp; p < 0.05 for TpTe); in MI patients, this difference was only significant for the maximum QT and QTp intervals (P < 0.05). In both patient groups, the QT and QTp dispersion was significantly greater compared to normal subjects (P < 0.05) but no consistent difference was observed in the TpTe dispersion among all three groups. In all subjects, the reproducibility of automatic measurement of QT and QTp intervals was high (coefficient of variation, CV, 1%-2%) and slightly lower for that of TpTe interval (2%-5%; p < 0.05). The reproducibility of QT, QTp, and TpTe dispersion was lower (12%-24%, 18%-28%, 16%-23% in normal subjects, MI and HC patients, respectively). The reliability of automatic measurement of QT, QTp, and TpTe intervals is high but the reproducibility of the repeated measurements of QT, QTp and TpTe dispersion is comparatively low.
BackgroundThe association between body mass index (BMI) and clinical outcomes of gastric cancer were still under debate. The aim of the present study was to investigate the impact of BMI on intraoperative conditions, postoperative complications and prognosis of gastric cancer.MethodsFrom October 2008 to March 2015, 1210 gastric cancer patients treated with D2 gastrectomy were enrolled in the present study. Patients were divided into three groups: low BMI group (BMI < 18.5 Kg/m2), normal BMI group (18.5 Kg/m2 ≤ BMI < 25.0 Kg/m2) and high BMI group (BMI ≥ 25.0 Kg/m2). Clinicopathological characteristics and prognosis of patients were recorded and analyzed. Propensity score matching was used to match patients in the three groups.ResultsThere were 107 patients in low BMI group (8.9%), 862 patients in normal BMI group (71.2%) and 241 patients in high BMI group (19.95%). Before matching, BMI was inversely associated with tumor size, tumor depth, lymph node metastasis (LNM) and tumor stage (all P < 0.05). After matching, the clinicopathological features were all comparable among the three groups (all P > 0.05). High BMI was associated with increased blood loss and operation time, and deceased number of retrieved lymph nodes (all P < 0.05). For postoperative complications, low BMI was associated with decreased rate of postoperative fever (P = 0.025). Age, BMI, tumor size, Borrmann type, pathological type, type of gastrectomy, tumor depth, LNM and tumor stage were risk factors for the prognosis of gastric cancer. Multivariate analysis showed that only BMI, tumor size, tumor depth and LNM were independent prognostic factors. The overall survival of patients with low BMI was significantly worse than patients with normal (P < 0.05) or high BMI (P < 0.05). However, the overall survival was comparable between patients with normal and high BMI (P > 0.05).ConclusionsBMI was inversely associated with tumor size, tumor depth, LNM and tumor stage. High BMI was associated with increased blood loss and operation time, and deceased number of retrieved lymph nodes. Low BMI was associated with decreased rate of postoperative fever and decreased survival.
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