A Zebrafish Compound Screen Reveals Modulation of Neutrophil Reverse Migration as an Anti-Inflammatory Mechanism

Diseases of failed inflammation resolution are common and largely incurable. Therapeutic induction of inflammation resolution is an attractive strategy to bring about healing without increasing susceptibility to infection. However, therapeutic targeting of inflammation resolution has been hampered by a lack of understanding of the underlying molecular controls. To address this drug development challenge, we developed an in vivo screen for proresolution therapeutics in a transgenic zebrafish model. Inflammation induced by sterile tissue injury was assessed for accelerated resolution in the presence of a library of known compounds. Of the molecules with proresolution activity, tanshinone IIA, derived from a Chinese medicinal herb, potently induced inflammation resolution in vivo both by induction of neutrophil apoptosis and by promoting reverse migration of neutrophils. Tanshinone IIA blocked proinflammatory signals in vivo, and its effects are conserved in human neutrophils, supporting a potential role in treating human inflammation and providing compelling evidence of the translational potential of this screening strategy

Experience of 3 Types of Commercially Available Photodiode Array in the Daresbury Laboratory Energy Dispersive EXAFS Detector System

The technique of Energy Dispersive EXAFS is well established as an excellent tool for dynamic measurements. Daresbury Laboratory has developed a photodiode array based detector system for synchrotron radiation Energy Dispersive EXAFS experiments which allows high quality data to be collected in time scales of less than a second [1]. In order to provide the highest quality system the performance of 3 different commercially available photodiode arrays has been evaluated. This paper presents the results of these evaluations and indicates the future direction of this project

Effects of sub-MIC concentrations of antibiotics on growth of and toxin production by Clostridium difficile

Effects on growth and toxin A production of sub-MIC concentrations of six different antibiotics were investigated in three strains of Clostridium difficile: reference strain NCTC 11223, a fully sequenced strain (630) and a locally endemic isolate (strain 338a). The antibiotics chosen for investigation were the agents used to treat C. difficile-associated disease (CDAD), i.e. vancomycin and metronidazole, and four antibiotics that are commonly involved in precipitating CDAD (amoxycillin, clindamycin, cefoxitin and ceftriaxone). Strains were cultured in sublethal concentrations of antibiotics (1/2, 1/4 and 1/8 MIC) over 104 h and growth and toxin A production were measured three times a day. Effects varied between strain and antibiotic. The most common effect on growth of the strains was to increase the initial lag period by approximately 4 h, compared with antibiotic-free controls; however, strain NCTC 11223, which has high-level clindamycin resistance (⩾ 512 μg ml−1), showed no lag whatsoever in comparison with the controls when grown in this antibiotic. The most common effect on production of toxin A was in the onset of toxin elaboration. Normally, toxins began to appear at low levels in the early stationary phase, before accumulating to high levels by the start of decline. In the presence of sub-MIC antibiotics, this onset appeared before that of the antibiotic-free controls. This effect was seen with metronidazole, amoxycillin and clindamycin, rarely with vancomycin and never with cefoxitin. These results suggest a very complex, strain-dependent relationship between the effects of growth and toxin production