Bmddsby JC et a]. EleMted sewn Msadar endothelial g M fador rxmmhkm m preedampsia. Hpw%g. 1998;17:283-291. bxkelsby JC d a]. VEGF I VEGF m -1 (m-1) mimics preedamptic plasma in intubkg uterine bbod vessel re!aMm m pregnancy Lab InvesI. 1599;79:1101-11. Ekckeky JC et al. The effeds of ~sarbr endo(helil growlh fador on edc#&l cells-a pctenbl role in peedampsia. h . J . ohst Gymxd 2oo0;182:17&183. 3. Y I 9 PROTECTION IN THE RAT HEART: A COMPARISON WITH ENDOTOXIN (LPS) K ZACHAROWSKI, S FRANK, M OTTO, PK CHATTERJEE, C THIEMERMANN

Methamidophos (CH3O(NH2)P(O)SCH3) and phosphoramidates, with the general structure RO(NH2)P(O)OC6H4-p-NO2, in which R = C2H5, C1CH2CH2, FCH2CH2 and F3CCH2, as well as (NH2)2P(O)OC6H4-p-NO2 were synthesized to investigate the relationship between the rates of inhibition and of spontaneous reactivation of AChE inhibited by these organophosphates and their potential as prophylactics against nerve agent poisoning. The phosphoramidates inhibit electric eel acetylcholinesterase (EEAChE), the bimolecular inhibition rate constants ranging from 5 x 10(4) to 3 x 10(6) M-1.min-1 at pH 7.5, 25 degrees C. The inhibited enzymes reactivate spontaneously, with half-lives ranging from 1.3 to 15 h at pH 7.5, 25 degrees C. These half-lives increase 2-4 fold when the temperature is raised to 37 degrees C. Reactivation is accelerated by micromolar concentrations of oximes such as obidoxime and HI-6. Aging of the inhibited enzymes was not observed. Nevertheless, reactivation appears to be incomplete for some of the inhibited enzymes. The title compounds seem promising as prophylactic agents against nerve agent intoxication.

No abstract

Staphylococcus aureus virulence has been associated with the production of phenol-soluble modulins (PSMs). These PSMs have distinct virulence functions and are known to activate, attract and lyse neutrophils. These PSM-associated biological functions are inhibited by lipoproteins in vitro. We set out to address whether lipoproteins neutralize staphylococcal PSM-associated virulence in experimental animal models. Serum from both LCAT an ABCA1 knockout mice strains which are characterised by near absence of high-density lipoprotein (HDL) levels, was shown to fail to protect against PSM-induced neutrophil activation and lysis in vitro. Importantly, PSM-induced peritonitis in LCAT−/− mice resulted in increased lysis of resident peritoneal macrophages and enhanced neutrophil recruitment into the peritoneal cavity. Notably, LCAT−/− mice were more likely to succumb to staphylococcal bloodstream infections in a PSM-dependent manner. Plasma from homozygous carriers of ABCA1 variants characterized by very low HDL-cholesterol levels, was found to be less protective against PSM-mediated biological functions compared to healthy humans. Therefore, we conclude that lipoproteins present in blood can protect against staphylococcal PSMs, the key virulence factor of community-associated methicillin resistant S. aureus.