Wilforol C

Serum C-Reactive Protein as a Prognostic Biomarker in Amyotrophic Lateral Sclerosis.[Pubmed:28384752]

JAMA Neurol. 2017 Jun 1;74(6):660-667.

Importance: Various factors have been proposed as possible candidates associated with the prognosis of amyotrophic lateral sclerosis (ALS); however, there is still no consensus on which biomarkers are reliable prognostic factors. C-reactive protein (CRP) is a biomarker of the inflammatory response that shows significant prognostic value for several diseases. Objective: To examine the prognostic significance of CRP in ALS. Design, Setting, and Participants: Patients' serum CRP levels were evaluated from January 1, 2009, to June 30, 2015, in a large cohort of patients with ALS observed by an Italian tertiary multidisciplinary center. Results were replicated in an independent cohort obtained from a population-based registry of patients with ALS. A post hoc analysis was performed of the phase 2 trial of NP001 to determine whether stratification by levels of CRP improves differentiation of responders and nonresponders to the drug. Main Outcomes and Measures: Serum CRP levels from the first examination were recorded to assess their effect on disease progression and survival. Results: A total of 394 patients with ALS (168 women and 226 men; mean [SD] age at diagnosis, 60.18 [13.60] years) were observed in a tertiary multidisciplinary center, and the analysis was replicated in an independent cohort of 116 patients with ALS (50 women and 66 men; mean [SD] age at diagnosis, 67.00 [10.74] years) identified through a regional population-based registry. Serum CRP levels in the 394 patients with ALS correlated with severity of functional impairment, as measured by total score on the ALS Functional Rating Scale-Revised, at first evaluation (r = -0.14818; P = .004), and with patient survival (hazard ratio, 1.129; 95% CI, 1.033-1.234; P = .007). Similar results were found in the independent cohort (hazard ratio, 1.044; 95% CI, 1.016-1.056; P

Discovery of novel 7-azaindole derivatives bearing dihydropyridazine moiety as c-Met kinase inhibitors.[Pubmed:28384549]

Eur J Med Chem. 2017 Jun 16;133:97-106.

A series of 7-azaindole derivatives bearing the dihydropyridazine scaffold were synthesized and evaluated for their c-Met kinase inhibitory, and antiproliferative activity against 4 cancer cell lines (HT29, A549, H460, U87MG) were evaluated in vitro. Most compounds showed moderate to excellent potency. Compared to foretinib, the most promising analog 34 (c-Met IC50: 1.06 nM, a multitarget tyrosine kinase inhibitor) showed a 6.4-, 7.8-, and 3.2-fold increase in activity against HT29, A549, and H460 cell lines, respectively. Structure activity relationship studies indicated that mono-EWGs (such as R2 = F) at 4-position of moiety D was a key factor in improving the antitumor activity.

Effect of water table variations and input of natural organic matter on the cycles of C and N, and mobility of As, Zn and Cu from a soil impacted by the burning of chemical warfare agents: A mesocosm study.[Pubmed:28384583]

Sci Total Environ. 2017 Oct 1;595:279-293.

A mesocosm study was conducted to assess the impact of water saturation episodes and of the input of bioavailable organic matter on the biogeochemical cycles of C and N, and on the behavior of metal(loid)s in a soil highly contaminated by the destruction of arsenical shells. An instrumented mesocosm was filled with contaminated soil taken from the "Place-a-Gaz" site. Four cycles of dry and wet periods of about one month were simulated for 276days. After two dry/wet cycles, organic litter sampled on the site was added above the topsoil. The nitrogen cycle was the most impacted by the wet/dry cycles, as evidenced by a denitrification microbial process in the saturated level. The concentrations of the two most mobile pollutants, Zn and As, in the soil water and in the mesocosm leachate were, respectively, in the 0.3-1.6mM and 20-110muM ranges. After 8months of experiment, about 83g.m(-3) of Zn and 3.5g.m(-3) of As were leached from the soil. These important quantities represent <1% of the solid stock of this contaminant. Dry/wet cycles had no major effect on Zn mobility. However, soil saturation induced the immobilization of As by trapping As V but enhanced As III mobility. These phenomena were amplified by the presence of bioavailable organic matter. The study showed that the natural deposition of forest organic litter allowed a part of the soil's biological function to be restored but did not immobilize all the Zn and As, and even contributed to transport of As III to the surrounding environment. The main hazard of this type of site, contaminated by organo-arsenic chemical weapons, is the constitution of a stock of As that may leach into the surrounding environment for several hundred years.