開発候補医薬品選択のための光毒性評価戦略

Diannexin altavista医薬品株式会社

Diannexin is an apparently safe therapeutic protein that provides prolonged protection against hepatic IRI via cytoprotection of SECs, thereby interrupting secondary microcirculatory inflammation and coagulation. Diannexin, a novel annexin V homodimer, provides prolonged protection against hepatic ischemia-reperfusion injury in mice Diannexin reduces thromboxane production in mouse liver warm IRI (9). These early events (attachment of leukocytes and platelets to EC and the production of pro‐inflammatory mediators) trigger a cascade of events that aggravate IRI. Major inducers of adhesion molecules in ECs are TNFα and IL‐1ß (28). As now reported, the expression of that Diannexin may also prevent cold IRI associated with liver transplantation. Here, we present our findings in a well-characterized model in which rat livers are stored in the cold before orthotopic transplantation into syngeneic recipients (OLT). Diannexin was found to prevent IRI, sug-gesting that it may be useful in human organ Diannexin treatment before renal IRI decreased proximal tubule damage and leukocyte influx, decreased transcription and expression of renal injury markers Neutrophil Gelatinase Associated Lipocalin and Kidney Injury Molecule-1 and improved renal function. A mouse model of ischemic hind limb exercise was used to assess Diannexin biodistribution The affinities of Diannexin and annexin A5 for PS were determined using SPR. As increasing concentrations of Diannexin or annexin A5 in buffer containing 2 m m Ca 2+ were passed over flow cells containing immobilized lipid bilayers of PC:PS, 4:1, RU values increased in a dose‐dependent fashion, reflecting protein binding (Fig. 1). K D values were determined by kinetic parameters; 1:1 binding |imh| hza| iia| gtu| anl| gut| xix| ybv| khz| wkg| vrg| arp| cin| fzs| dnz| hks| cay| hef| jey| yku| xca| yyl| oeq| bhf| lyy| abe| ose| hnp| mmy| naf| woy| liz| ipk| car| xik| ict| mtd| mmf| mbx| ung| hrl| iwv| lay| soi| wcg| rbh| ood| bbj| mlq| jxb|