Indole ring oxidation by activated leukocytes prevents the production of hypochlorous acid

Hypochlorous acid (HOCl) released by activated leukocytes has been implicated in the tissue damage that characterizes chronic inflammatory diseases. In this investigation, 14 indole derivatives, including metabolites such as melatonin, tryptophan and indole-3-acetic acid, were screened for their ability to inhibit the generation of this endogenous oxidant by stimulated leukocytes. The release of HOCl was measured by the production of taurine-chloramine when the leukocytes (2 x 10(6) cells/mL) were incubated at 37ºC in 10 mM phosphate-buffered saline, pH 7.4, for 30 min with 5 mM taurine and stimulated with 100 nM phorbol-12-myristate acetate. Irrespective of the group substituted in the indole ring, all the compounds tested including indole, 2-methylindole, 3-methylindole, 2,3-dimethylindole, 2,5-dimethylindole, 2-phenylindole, 5-methoxyindole, 6-methoxyindole, 5-methoxy-2-methylindole, melatonin, tryptophan, indole-3-acetic acid, 5-methoxy-2-methyl-3-indole-acetic acid, and indomethacin (10 µM) inhibited the chlorinating activity of myeloperoxidase (MPO) in the 23-72% range. The compounds 3-methylindole and indole-3-acetic acid were chosen as representative of indole derivatives in a dose-response study using purified MPO. The IC50 obtained were 0.10 ± 0.03 and 5.0 ± 1.0 µM (N = 13), respectively. These compounds did not affect the peroxidation activity of MPO or the production of superoxide anion by stimulated leukocytes. By following the spectral change of MPO during the enzyme turnover, the inhibition of HOCl production can be explained on the basis of the accumulation of the redox form compound-II (MPO-II), which is an inactive chlorinating species. These results show that indole derivatives are effective and selective inhibitors of MPO-chlorinating activity.

In silico analysis identifies a C3HC4-RING finger domain of a putative E3 ubiquitin-protein ligase located at the C-terminus of a polyglutamine-containing protein

Almost identical polyglutamine-containing proteins with unknown structures have been found in human, mouse and rat genomes (GenBank AJ277365, AF525300, AY879229). We infer that an identical new gene (RING) finger domain of real interest is located in each C-terminal segment. A three-dimensional (3-D) model was generated by remote homology modeling and the functional implications are discussed. The model consists of 65 residues from terminal position 707 to 772 of the human protein with a total length of 796 residues. The 3-D model predicts a ubiquitin-protein ligase (E3) as a binding site for ubiquitin-conjugating enzyme (E2). Both enzymes are part of the ubiquitin pathway to label unwanted proteins for subsequent enzymatic degradation. The molecular contact specificities are suggested for both the substrate recognition and the residues at the possible E2-binding surface. The predicted structure, of a ubiquitin-protein ligase (E3, enzyme class number 6.3.2.19, CATH code 3.30.40.10.4) may contribute to explain the process of ubiquitination. The 3-D model supports the idea of a C3HC4-RING finger with a partially new pattern. The putative E2-binding site is formed by a shallow hydrophobic groove on the surface adjacent to the helix and one zinc finger (L722, C739, P740, P741, R744). Solvent-exposed hydrophobic amino acids lie around both zinc fingers (I717, L722, F738, or P765, L766, V767, V733, P734). The 3-D structure was deposited in the protein databank theoretical model repository (2B9G, RCSB Protein Data Bank, NJ).

Novel retrograde puncture method to establish preperitoneal space for laparoscopic direct inguinal hernia repair with internal ring suturing

The aim of this study was to explore the clinical efficacy of a novel retrograde puncture approach to establish a preperitoneal space for laparoscopic direct inguinal hernia repair with inguinal ring suturing. Forty-two patients who underwent laparoscopic inguinal hernia repair with retrograde puncture for preperitoneal space establishment as well as inguinal ring suturing between August 2013 and March 2014 at our hospital were enrolled. Preperitoneal space was successfully established in all patients, with a mean establishment time of 6 min. Laparoscopic repairs were successful in all patients, with a mean surgical time of 26±15.1 min. Mean postoperative hospitalization duration was 3.0±0.7 days. Two patients suffered from postoperative local hematomas, which were relieved after puncturing and drainage. Four patients had short-term local pain. There were no cases of chronic pain. Patients were followed up for 6 months to 1 year, and no recurrence was observed. Our results demonstrate that preperitoneal space established by the retrograde puncture technique can be successfully used in adult laparoscopic hernioplasty to avoid intraoperative mesh fixation, and thus reduce medical costs.

Canot Despujols [sur la Seine, près de l'île de la Jatte] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 58602

23/3/20, hydroglisseur Despujols [record de vitesse, sur la Seine, près de l'île de la Jatte] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 58614

[23/3/20, équipage du canot Despujols, record de vitesse, sur la Seine, près de l'île de la Jatte] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 58616

9/5/20, traversée de Paris [à l'aviron], équipe de la Haute Seine, gagnant des 8 : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 59220

9/5/20, traversée de Paris à l'aviron, [équipe de la] Haute Seine : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 59221

Convention collective de travail des employés de maison du département de la Seine. [Ed. mise à jour au... Arrêté du Secrétariat d'Etat au travail et à la sécurité sociale du 13 septembre 1957.]. 15 février 1962

[Convention collective. Employés de maison. Seine. 1960-]

Convention collective de travail des employés de maison du département de la Seine. [Ed. mise à jour au... Arrêté du Secrétariat d'Etat au travail et à la sécurité sociale du 13 septembre 1957.]. 1er septembre 1964

[Convention collective. Employés de maison. Seine. 1960-]

Convention collective de travail des employés de maison du département de la Seine. [Ed. mise à jour au... Arrêté du Secrétariat d'Etat au travail et à la sécurité sociale du 13 septembre 1957.]. 1er septembre 1967

[Convention collective. Employés de maison. Seine. 1960-]

Der Dialekt von Bergün und seine Stellung innerhalb der rätoromanischen Mundarten Graubündens / von C. Martin Lutta ; [Geleitwort von L. Gauchat, J. Jud und F. Frankhauser]

Collection : Beihefte zur "Zeitschrift für romanische Philologie" ; 71. Heft