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BACKGROUND: Cardiac remodeling after acute myocardial infarction is regulated by components of the extracellular matrix. The 47 kD heat shock protein 47 (HSP47) is a collagen-specific molecular chaperone that plays a major role during procollagen processing and/or secretion. OBJECTIVE: The purpose of the study was to determine whether HSP47 inhibition can mitigate ligated left anterior descending (LAD) coronary artery-induced myocardial infarction in rats. METHODS: Rats were randomly divided into four experimental groups and subjected to the following treatments: 1) intravenous (IV) administration of saline; 2) ligation of the LAD coronary artery; 3) ligation of the LAD coronary artery + IV administration of HSP47 antisense oligonucleotides; or 4) IV administration of HSP47 antisense oligonucleotides. We investigated cardiac histopathology, performed immunoblot and immunohistochemical analyses, and examined cardiac function. RESULTS: Rats with ligated LAD coronary artery experienced upregulation of HSP47 expression, remodeling of the left ventricle, and cardiac dysfunction. In contrast, rats with ligated LAD coronary artery treated with HSP47 antisense oligonucleotides had significantly reduced HSP47 expression, cardiac remodeling, and improved cardiac function. Intravenous (IV) administration of HSP47 antisense oligonucleotides alone had no effect on cardiac morphology. CONCLUSION: The data strongly support the idea that changes in the extracellular matrix and its components are important determinants of cardiac remodeling after myocardial infarction. [ABSTRACT FROM AUTHOR]

Abstract. Objective:  Sivelestat sodium hydrate (sivelestat) is a specific synthetic inhibitor of neutrophil elastase (NE). Various studies suggest that sivelestat treatment reduces inflammation. In this study, we tested the hypothesis that sivelestat acts as an inhibitor of inflammatory mediators and prevents nuclear factor-kB (NF-kB) activation. Methods:  In the presence and absence of sivelestat, the mouse macrophage cell line RAW 264.7 was stimulated with lipopolysaccharide (LPS) and the levels of inflammatory mediators (TNF-α, IL-6 and high mobility group box 1 (HMGB1)) and nitrite in the cell supernatant were measured, along with inducible nitric oxide synthase (iNOS) expression. Results:  While LPS administration increased the secretion of inflammatory mediators and nitric oxide (NO), sivelestat decreased the secretion of these mediators. Cell signaling studies demonstrated that sivelestat decreased NF-kB activation by inhibiting IkB phosphorylation. Conclusion:  Sivelestat may inhibit the various inflammatory mediators through NF-kB inhibition. [ABSTRACT FROM AUTHOR]

Abstract. Objectives:  To examine whether moderate changes in cell culture temperature influence the production of various cytokines and associated mediators of inflammation. Methods:  We performed lipopolysaccharide (LPS) stimulation of the murine macrophagic RAW264.7 cell line under hyperthermic (40 �C), normothermic (37 �C) and hypothermic (34 �C) conditions. We then measured the levels of heat shock protein 70 (HSP70), heat shock factor protein (HSF) and nuclear factor–kB (NF-kB) dimers (p50 and p65) in the cells, and the levels of high mobility group box 1 (HMGB1) and the cytokines tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β) and interleukin 6 (IL-6) in the culture supernatants. Results:  Levels of HMGB1, IL-1β, IL-6, and TNF-α, as well as NF-kB dimers (p50 and p65), were all reduced following LPS stimulation at 40 �C and 34 �C compared with those at 37 �C. Levels of HSP70 and HSF increased at 40 �C and 34 �C. Conclusions:  The application of moderate hyperthermia and hypothermia after LPS-induced cell activation attenuated the inflammatory response and reduced the likelihood of cell damage. These findings suggest that moderate temperature changes modulate the inflammatory response and could be a useful therapy against sepsis. [ABSTRACT FROM AUTHOR]

: Background No data for patients with failed back surgery syndrome (FBSS) based on the location of adhesions separated by epiduroscopic adhesiolysis have been reported. : Methods We performed epiduroscopic adhesiolysis on 28 FBSS patients to examine the impact of differences in the locations of the separated regions on the treatment results. We performed fluoroscopic imaging through the sacral hiatus to assess the condition of adhesions in the epidural space during the post-adhesiolysis observation period. : Results In patients in whom only the epidural space was separated by adhesiolysis, there was a significant improvement in the Roland–Morris disability questionnaire (RDQ) score until 12 weeks after adhesiolysis, but the score gradually returned to the preoperative value thereafter. Among patients in whom the nerve root responsible for radicular pain was separated, there was a long-term improvement in the RDQ, Oswestry disability index 2.0 (ODI), and Japanese Orthopedic Association Assessment of Treatment (JOA) scores. Among patients in whom both the epidural space and the nerve root responsible for pain were separated, there was a 12 week improvement in the RDQ score and 24 week improvements in the ODI and JOA scores. : Conclusions Progressive epidural imaging after adhesiolysis suggested that pain was caused by re-adhesion around the nerve root. Since re-adhesion of the nerve root required some time, the effect of adhesiolysis was maintained for extended periods in these cases. We suggest that epiduroscopic adhesiolysis is an effective therapy for FBSS patients, and that adhesiolysis of the nerve root may exhibit the long-term (24 weeks) efficacy in patients with pain. [ABSTRACT FROM AUTHOR]