2-Phenyl-5-(trifluoro­meth­yl)pyrazol-3(2H)-one

The title compound, C10H7F3N2O, is an analogue of pyrazolone derivatives with potential analgesic and anti-inflammatory properties. Its mol­ecular structure consists of phenyl and pyrazol-3(2H)-one units with a dihedral angle between the mean planes of the rings of 33.0 (1)°. The crystal structure is stabilized by an inter­molecular hydrogen bond between the N—H group and the carbonyl O atom of the pyrazol-3(2H)-one ring which links the mol­ecules into supra­molecular C(5) chains along [001] and by weak π–π stacking inter­actions between the phenyl rings [centroid-centroid distance = 3.881 (2) Å]. The F atoms are disordered over two positions with refined site occupancies of 0.768(11) and 0.232(11)

Italian guidelines for primary headaches: 2012 revised version

The first edition of the Italian diagnostic and therapeutic guidelines for primary headaches in adults was published in J Headache Pain 2(Suppl. 1):105–190 (2001). Ten years later, the guideline committee of the Italian Society for the Study of Headaches (SISC) decided it was time to update therapeutic guidelines. A literature search was carried out on Medline database, and all articles on primary headache treatments in English, German, French and Italian published from February 2001 to December 2011 were taken into account. Only randomized controlled trials (RCT) and meta-analyses were analysed for each drug. If RCT were lacking, open studies and case series were also examined. According to the previous edition, four levels of recommendation were defined on the basis of levels of evidence, scientific strength of evidence and clinical effectiveness. Recommendations for symptomatic and prophylactic treatment of migraine and cluster headache were therefore revised with respect to previous 2001 guidelines and a section was dedicated to non-pharmacological treatment. This article reports a summary of the revised version published in extenso in an Italian version

Testing the “read-across hypothesis” by investigating the effects of ibuprofen on fish

Supplementary data related to this article can be found at http:// dx.doi.org/10.1016/j.chemosphere.2016.08.041Human pharmaceuticals present in the environment have the potential to cause adverse effects on non-target organisms. The “read-across hypothesis” stipulates that pharmaceuticals will exhibit similar biological effects across species (e.g. human and fish) if the molecular target has been conserved and the effective drug concentrations are reached (Cmax). We tested this hypothesis by evaluating if ibuprofen, a non-selective inhibitor of prostaglandins and the cyclooxygenase (COX) enzyme, can mimic its primary effect in humans, on fish, at comparable plasma concentrations. The endpoints, “prostaglandin E metabolite” (PGEM) levels and the mRNA expression of COX (ptgs gene), were measured in the gills of control and exposed fathead minnows (Pimephales promelas), using enzyme-immunoassay and quantitative real-time PCR (qPCR). Fish were exposed, for 24-72 h, to measured water concentrations of 9 (n= 12), 370 (n= 40) and 470 μg ibuprofen/L (n= 12). Water and blood plasma concentrations were determined using LC-MS/MS. Results showed that PGEM levels in fish exposed to 370 and 470 μg ibuprofen/L were significantly decreased compared to control fish, when mean plasma ibuprofen concentrations were 1.8 to 5.6-fold below the Cmax. The plasma ibuprofen concentrations and PGEM levels varied greatly between individuals. In fish exposed to 9 μg ibuprofen/L, when the mean plasma ibuprofen concentration was 224-fold below Cmax, no change in PGEM levels was observed. These data provide evidence for the read-across hypothesis, but suggest establishing a direct dose-response between internal plasma and PGEM is difficult, and would require significantly larger numbers of fish to overcome the inter-individual variation.This work was supported by Biotechnology and Biological Sci- ences Research Council (BBSRC) Industrial CASE Partnership Stu- dentship BB/I53257X/1 with AstraZeneca Safety Health and Environment Research Programme