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Lines 962b-964 of Aristophanes’ Knights raise a remarkably complex problem. There is no consensus on the interpretation of the metaphorical value of the rare term µ?????, a vulgar equivalent of ?s???, wineskin (§ 1). After a complete analysis of the other occurrences of µ????? in Aristophanes (frr. 103, 308 and 933: §§ 2-4), this article suggests a new interpretation of the lines in the Knights (§ 5). The barbarian slave Paphlagon/Cleon threatens Demos to tan his hide by turning it into a µ?????, i. e., to abuse him as a violent erastes would sexually abuse his eromenos. Cleon aspires to dominate (the) Demos (§ 6). more...

Several studies report that among the antioxidant agents used to reduce injury after myocardial ischemia/reperfusion, analogues of vitamin E (VE) seem to have a significant efficacy. Raxofelast is a potent antioxidant agent under investigation, structurally related to VE, having an excellent bioavailability and favourable physicochemical properties. We assessed raxofelast in a rat model of myocardial damage induced by 1 h of left coronary artery occlusion followed by 6 h of reperfusion. Myocardial ischemia/reperfusion produced: wide tissue necrosis (50.3±10.3%); membrane peroxidation, evaluated by assessing cardiac malondialdehyde (MAL) (87.8±15.8 nmol/g tissuev9.53±2.4 nmol/g tissue) and plasma conjugated dienes (CD) (8.73±1.86 ΔABS/mlv1.61±0.45 ΔABS/ml); endogenous antioxidant wasting [cardiac VE=23.5±10.2 nmol/g tissuev61.4±13.4 nmol/g tissue, cardiac reduced glutatione (GSH)=2.15±1.23μmol/g proteinv7.34±0.92μmol/g protein and cardiac superoxide dismutase (SOD)=8.9±4.1 U/mg proteinv17.5±4.2 U/mg protein]; depressed mean arterial blood pressure (MAP) (61.4±5.8 mmHgv85.3±6.2 mmHg); heart rate (HR) (275±35 beats/minv368±34 beats/min) and left-ventricular derivative developed force (LV dP/dtmax) (1050±187 mmHg/sv2520±194 mmHg/s); and cardiac neutrophil accumulation, evaluated by assessing cardiac myeloperoxidase (MPO) (9.23±2.1 U/g tissuev0.92±0.12 U/g tissue). Administration of raxofelast (25, 50 and 100 mg/kg i.p. 5 min after occlusion) limited myocardial necrosis (22.3±14.8%P<0.005, following the highest dose), reduced lipid peroxidation (MAL=43.5±14.7 nmol/g tissueP<0.001 and CD=4.01±2.21 ΔABS/mlP<0.001, following the highest dose), restored the endogenous antioxidants VE (52.8±14.2 nmol/g tissueP<0.001, following the highest dose), SOD (14.2±2.7 U/mg proteinP<0.001, following the highest dose) and GSH (4.92±1.33μmol/g proteinP<0.005, following the highest dose), improved hemodynamic parameters (MAP=68.1±5.3 mmHgP<0.05, HR=317±27 beats/minP<0.05, LV dP/dtmax=1427±143 mmHg/sP<0.05, following the highest dose) and reduced myocardial neutrophil infiltration (MPO=5.1±1.5 U/g tissueP<0.001, following the highest dose). These data suggest that raxofelast could be considered a useful drug to reduce myocardial infarction. more...

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Background: Nuclear factor-κB (NF-κB) is a ubiquitous rapid response transcription factor involved in inflammatory reactions which exerts its effect by expressing cytokines, chemokines, and cell adhesion molecules. Oxidative stress causes NF-κB activation. IRFI 042 is a novel dual vitamin E-like antioxidant and we, therefore, investigated its ability to protect the heart from oxidative stress and to halt the inflammatory response in a model of myocardial ischaemia–reperfusion injury. Methods: Anaesthetized rats were subjected to total occlusion (45 min) of the left main coronary artery followed by 5-h reperfusion (MI/R). Sham myocardial ischaemia rats (sham-operated rats) were used as controls. Myocardial necrosis, cardiac output, cardiac and plasma vitamin E levels, myocardial malondialdehyde (MAL), cardiac SOD activity and elastase content (an index of leukocyte infiltration), hydroxyl radical (OH⋅) formation, cardiac amount of mRNA codifying for ICAM-1 (evaluated by the means of reverse transcriptase polymerase chain reaction) and ICAM-1 immunostaining in the at-risk myocardium were investigated. NF-κB activation and the inhibitory protein of NF-κB, I-κBα, were also studied in at-risk myocardium by using electrophoretic mobility shift assay (EMSA) and Western blot analysis, respectively. Results: The ischaemia–reperfusion model produced wide heart necrosis (area at risk−necrotic area=52±5%; necrotic area−left ventricle=28±3%), increased cardiac MAL, an index of lipid peroxidation (area at risk=62.5±3.9 nmol/g tissue; necrotic area=80.3±5.1 nmol/g tissue), induced tissue neutrophil infiltration, and caused a marked decrease in endogenous antioxidants. Furthermore, myocardial ischaemia plus reperfusion caused in the area at risk peak message for ICAM-1 at 3 h of reperfusion and increased cardiac ICAM-1 immunostaining at 5 h of reperfusion. NF-κB activation was also evident at 0.5 h of reperfusion and reached its maximum at 2 h of reperfusion. I-κBα was markedly decreased at 45 min of occlusion; peak reduction was observed at 1 h of reperfusion and thereafter it was gradually restored. Intraperitoneal administration of IRFI 042 (5, 10, 20 mg/kg, 5 min after reperfusion) reduced myocardial necrosis expressed as a percentage either of the area at risk (18±4%) or the total left ventricle (11±2%), and improved cardiac output. This treatment also limited membrane lipid peroxidation in the area at risk (MAL=14.3±2.5 nmol/g tissue) and in the necrotic area (MAL=26.5±3.7 nmol/g tissue), restored the endogenous antioxidants vitamin E and superoxide dismutase, and inhibited detrimental hydroxyl radical formation. Finally, IRFI 042 blocked the activation of NF-κB, reduced cardiac ICAM-1 expression, and blunted tissue elastase content, an index of leukocytes accumulation at the site of injury. Conclusions: Our data suggest that IRFI 042 is cardioprotective during myocardial infarction by limiting reperfusion-induced oxidative stress and by halting the inflammatory response. more...

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option. more...