Ceftaroline fosamil demonstrated high clinical cure and microbiological response rates in hospitalized patients with CAP of PORT risk class III or IV. Ceftaroline fosamil was well tolerated, with a safety profile similar to that of ceftriaxone and consistent with the cephalosporin class. In this study, ceftaroline fosamil was an effective and well-tolerated treatment option for CAP.

Endothelium-dependent contractions to acetylcholine and endothelium-independent contractions to oxygen-derived free radicals in the aorta of the spontaneously hypertensive rat (SHR) are mediated by an unidentified product of the cyclooxygenase pathway of arachidonic acid metabolism. To determine the role of thromboxane A 2 (TXA 2 ) or prostaglandin H 2 (PGH 2 ) in these contractions, rings of the thoracic aorta of SHR were suspended in organ chambers for measurement of isometric force. Acetylcholine caused endothelium-dependent contractions in quiescent rings from SHR aortas. Oxygen-derived free radicals generated with xanthine plus xanthine oxidase caused contractions in rings without endothelium. Dazoxiben E ndothelium-dependent contractions to acetylcholine and endothelium-independent contractions to oxygen-derived free radicals of the aorta of spontaneously hypertensive rats (SHR) are mediated by activation of cyclooxygenase.

To determine if oxygen-derived free radicals are mediators of endothelium-dependent contractions to acetylcholine in the aorta of spontaneously hypertensive rats (SHR), the mechanism of contraction to xanthine plus xanthine oxidase was studied. Rings, with and without endothelium, of thoracic aorta from normotensive Wistar-Kyoto (WKY) rats and SHR were suspended in organ chambers for isometric tension recording. Oxygen-derived free radicals caused concentration-dependent contractions; these contractions were twice as large in the aortas of SHR than in WKY rats. Deferoxamine reversed the response to xanthine oxidase to a small relaxation. Either allopurinol, superoxide dismutase, or catalase, or the combination of superoxide dismutase plus catalase reduced the contractions. Diltiazem inhibited the response to xanthine oxidase; in contrast, phentolamine plus propranolol did not affect it. Indomethacin and meclofenamate, but not tranylcypromine or dazoxiben blocked the contractions. Endotheliumdependent contractions to acetylcholine in aortas from the SHR were not affected by deferoxamine or superoxide dismutase plus catalase. These data suggest that hydroxyl radicals cause contractions in the rat aorta, which are dependent on extracellular calcium and mediated by activation of the cyclooxygenase in the vascular smooth muscle. The augmented contractions in the hypertensive strain are due to an increased reactivity of the smooth muscle to oxygenderived free radicals. However, the lack of effect of the scavengers on endothelium-dependent contractions to acetylcholine suggests that the endothelium-derived contracting factor is chemically different from oxygen-derived free radicals. (Hypertension 1989;13:859-864)

Low-grade inflammation as evidenced by elevated preprocedural serum CRP-levels is an independent predictor of adverse outcome after coronary stent implantation, suggesting that a systemically detectable inflammatory activity is associated with proliferative responses within successfully implanted stents.

Acetylcholine evokes the simultaneous release of endothelium-derived relaxing and contracting factors in aortas from spontaneously hypertensive rats. Only relaxing factors are released in aortas from normotensive controls. Experiments were designed to determine whether inhibitors of endotheliumdependent relaxations modify endothelium-dependent contractions. Rings of thoracic aortas of normotensive and spontaneously hypertensive rats, with and without endothelium, were suspended in organ chambers for isometric tension recording. Oxyhemoglobin (a scavenger of endothelium-derived relaxing factor) and jV G -monomethyl L-arginine (an inhibitor of nitric oxide formation) augmented the contractions to acetylcholine. Methylene blue (an inhibitor of soluble guanylate cyclase) and superoxide dismutase (a scavenger of superoxide anions) did not modify these contractions. The contractions in the presence of oxyhemoglobin or JV G -monomethyl L-arginine, like those in untreated rings, were endothelium-dependent; they only occurred in aortas from spontaneously hypertensive rats and were abolished by indomethacin. The contractions to acetylcholine in the presence of oxyhemoglobin were not affected by superoxide dismutase or deferoxamine. These data suggest that endothelium-derived relaxing factor inhibits endothelium-dependent contractions to acetylcholine in the spontaneously hypertensive rat aorta, probably by chemical inactivation of the endothelium-derived contracting factor rather than by stimulation of guanylate cyclase or scavenging of oxygen-derived free radicals. A cetylcholine causes the simultaneous release of / \ endothelium-derived relaxing and contracting A. V . factors in aortas from spontaneously hypertensive rats (SHR).1 -2 Only relaxing factors are released from normotensive controls, Wistar-Kyoto (WKY) rats. -2 In rings contracted with norepinephrine, the concomitant release of endothelium-derived contracting factor from SHR aortas leads to reduced endothelium-dependent relaxations compared with aortas from WKY rats.1 In quiescent rings, acetylcholine causes endothelium-dependent contractions only in aortas from SHR but not from WKY rats.1 The nature of the contracting factors has not been identified so far. It appears to be an unstable product of cyclooxygenase (most likely endoperoxides) that stimulates thromboxane A 2 /prostaglandin H 2 receptors on vascular smooth muscle.1 -3 -5 The purpose of the present study was to determine whether endothelium-dependent contrac- tions to acetylcholine are modified by the simultaneous release of endothelium-derived relaxing factor. MethodsThe experiments were performed on the thoracic aorta from male, normotensive WKY rats and age-and weight-matched SHR (30-34 weeks old; weight, WKY 381 + 7 g, n=5, SHR 391+4 g, n = 16) (Harlan Sprague Dawley, Indianapolis, Ind.). Systolic blood pressure was determined by an indirect tail-cuff method in the unanesthetized animal before the experiment (WKY 122±8 mm Hg, SHR 202+4 mm Hg; p<0.05). The thoracic aorta was excised under anest...