Clinical outcome and olanzapine plasma levels in acute schizophrenia

Purpose: This open label study was performed to evaluate the reletionship between the plasma concentration of olanzapine and the response in acute schizophrenic inpatients. Material and methods. A total of 54 inpatients, 38 males and 16 females, age ranging from 18 to 75 years, affected by schizophrenia during an exacerbation phase were included in the study. Olanzapine (OLZ) was started at a dose of 5-20 mg/day and was increased to a mean dose of 15.27 mg +/- 5.53 sd. Patients were evaluated at baseline, and after 2 weeks, by using BPRS, PANNS, HRS-D, EPSE and ACS. Results.BPRS and total PANSS showed a statistically significant improvement at the end of the study. Olanzapine plasma levels (PL)ranged from 5 to 120 ng/ml (mean 33.15 ng/ml; sd 28.28) and showed a positive correlation with OLZ dosage. A significant curvilinear correlation between OLZ PL and clinical improvement (BPRS, PANSS and HRS-D percent of amelioration) was observed. Conclusion. Olanzapine plasma level determination seems to be a useful tool in optimizing acute treatment particularly for more problematic cases

Identification of environmental factors that promote intestinal inflammation

Genome-wide association studies have identified risk loci linked to inflammatory bowel disease (IBD)1-a complex chronic inflammatory disorder of the gastrointestinal tract. The increasing prevalence of IBD in industrialized countries and the augmented disease risk observed in migrants who move into areas of higher disease prevalence suggest that environmental factors are also important determinants of IBD susceptibility and severity. However, the identification of environmental factors relevant to IBD and the mechanisms by which they influence disease has been hampered by the lack of platforms for their systematic investigation. Here we describe an integrated systems approach, combining publicly available databases, zebrafish chemical screens, machine learning and mouse preclinical models to identify environmental factors that control intestinal inflammation. This approach established that the herbicide propyzamide increases inflammation in the small and large intestine. Moreover, we show that an AHR-NF-κB-C/EBPβ signalling axis operates in T cells and dendritic cells to promote intestinal inflammation, and is targeted by propyzamide. In conclusion, we developed a pipeline for the identification of environmental factors and mechanisms of pathogenesis in IBD and, potentially, other inflammatory diseases

Identification of environmental factors that promote intestinal inflammation

Genome-wide association studies have identified risk loci linked to inflammatory bowel disease (IBD)(1)-a complex chronic inflammatory disorder of the gastrointestinal tract. The increasing prevalence of IBD in industrialized countries and the augmented disease risk observed in migrants who move into areas of higher disease prevalence suggest that environmental factors are also important determinants of IBD susceptibility and severity(2). However, the identification of environmental factors relevant to IBD and the mechanisms by which they influence disease has been hampered by the lack of platforms for their systematic investigation. Here we describe an integrated systems approach, combining publicly available databases, zebrafish chemical screens, machine learning and mouse preclinical modelsto identify environmental factorsthat control intestinal inflammation. This approach established that the herbicide propyzamide increases inflammation in the small and large intestine. Moreover, we show that an AHR-NF-kappa B-C/EBP beta signalling axis operates in T cells and dendritic cells to promote intestinal inflammation, and is targeted by propyzamide. In conclusion, we developed a pipeline forthe identification of environmental factors and mechanisms of pathogenesis in IBD and, potentially, other inflammatory diseases.Y