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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).

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.

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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.

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