Synthesis and pharmacological evaluation of 1,1,3-substituted urea derivatives as potent TNF-alpha production inhibitors.

A three substituted urea derivative, SA13353 (compound 1a), exhibited potent inhibitory activity against lipopolysaccharide (LPS)-induced TNF-alpha production. We focused on the 1,1-substituted moiety (R(1) and R(2)) of SA13353 and investigated substituent effects of this moiety on LPS-induced TNF-alpha production by oral administration in rats. The synthesis of the urea derivatives was performed rapidly in a one-pot manner using a manual synthesizer. Several compounds containing hydrophobic substituents at this moiety showed more potent inhibitory activities than SA13353.

Isthmus of a horseshoe kidney overlying a ruptured abdominal aortic aneurysm: a case report.

Horseshoe kidney is a rare congenital anomaly showing various degrees of fusion and accessory blood supply. Coexistence of horseshoe kidney and aortic aneurysm therefore presents a technical challenge to vascular surgeons. We report an 83-year-old woman with a ruptured abdominal aortic aneurysm associated with horseshoe kidney. Preoperative computed tomography (CT) showed discontinuity of the aneurysm wall in relation to the isthmus of the horseshoe kidney, and rupture of the aneurysm into the retroperitoneal space. The aneurysm was exposed via a transperitoneal approach, and grafting was performed successfully together with division of the isthmus of the horseshoe kidney. Renal function showed no impairment postoperatively.

Time-dependent regional myocardial denervation as a nonspecific response to transmyocardial laser revascularization.

BACKGROUND: It is known that denervation occurs in the regions of myocardium treated by laser transmyocardial revascularization (TMR). The purpose of this study was to determine when regional denervation occurs in the early postoperative period and whether or not it is specific to laser TMR when compared with TMR using ultrasonically activated energy. METHODS: Dogs with normal myocardium underwent either holmium:yttrium-aluminum-garnet laser TMR, TMR using an ultrasonic activated surgical blade, or a thoracotomy as sham operation. The responses of mean arterial pressure to topical application of bradykinin were examined at 3 time points: before, 1 hour after, and 2 weeks after surgery. The hearts were excised for Western blot and immunohistochemical analysis. RESULTS: The response of mean arterial pressure to bradykinin was similarly attenuated in both TMR groups 1 hour after treatment and decreased to almost none after 2 weeks compared with pretreatment values. By comparison, the sham group showed persistent responses at both time points. Tissue tyrosine hydroxylase content of the treated area decreased significantly compared with the non-treated area in both TMR groups. Immunohistochemistry using anti-Protein Gene Product 9.5 and anti-synaptophysin antibodies showed a significant decrease in the number of positive nerve fibers in both TMR treatment groups compared with the sham group. CONCLUSIONS: Transmyocardial revascularization caused partial alteration in myocardial innervation immediately after TMR. Tissue responses may continue to occur for the first 2 weeks after treatment. Tissue responses may also contribute to the development of denervation regardless of the energy source in non-ischemic canine myocardium.

Enantioselective Ring Opening of Epoxides with 4-Methoxyphenol Catalyzed by Gallium Heterobimetallic Complexes: An Efficient Method for the Synthesis of Optically Active 1,2-Diol Monoethers.

Useful chiral building blocks such as 1,2-diols can be obtained by the enantioselective ring opening of achiral epoxides with oxygen nucleophiles. The ring opening is carried out effectively (up to 94 % ee) with 4-methoxyphenol and catalytic amounts of gallium complexes. The novel complex GaSO 1 displays a particularly high catalytic activity.