New Biochemical Insights into the Mechanisms of Pulmonary Arterial Hypertension in Humans

Diagnosis of pulmonary arterial hypertension (PAH) is difficult due to the lack of specific clinical symptoms and biomarkers, especially at early stages. We compared plasma metabolic fingerprints of PAH patients (n = 20) with matched healthy volunteers (n = 20) using, for the first time, untargeted multiplatform metabolomics approach consisting of high-performance liquid and gas chromatography coupled with mass spectrometry. Multivariate statistical analyses were performed to select metabolites that contribute most to groups' classification (21 from liquid in both ionization modes and 9 from gas chromatography-mass spectrometry). We found metabolites related to energy imbalance, such as glycolysis-derived metabolites, as well as metabolites involved in fatty acid, lipid and amino acid metabolism. We observed statistically significant changes in threitol and aminomalonic acid in PAH patients, which could provide new biochemical insights into the pathogenesis of the disease. The results were externally validated on independent case and control cohorts, confirming up to 16 metabolites as statistically significant in the validation study. Multiplatform metabolomics, followed by multivariate chemometric data analysis has a huge potential for explaining pathogenesis of PAH and for searching potential and new more specific and less invasive markers of the disease.This research was supported by the Polish National Science Center (2014/13/N/NZ7/04231), the Spanish Ministry of Economy and Competitiveness (MINECO) (SAF2014-58920R), by the Fondo de Investigacion Sanitaria del Instituto de Salud Carlos III and co-funding by Fondo Europeo de Desarrollo Regional (FEDER) (PI14-01427), and by the quality-promoting subsidy from the Ministry of Science and Higher Education of Poland, Leading National Research Centre (KNOW programme 2012-2017). The CNIC is supported by the Spanish Ministry of Economy and Competitiveness and the Pro-CNIC Foundation, and is a Severo Ochoa Center of Excellence (MINECO award SEV-2015-0505). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.S

New biochemical insights into the mechanisms of pulmonary arterial hypertension in humans

Diagnosis of pulmonary arterial hypertension (PAH) is difficult due to the lack of specific clinical symptoms and biomarkers, especially at early stages. We compared plasma metabolic fingerprints of PAH patients (n = 20) with matched healthy volunteers (n = 20) using, for the first time, untargeted multiplatform metabolomics approach consisting of high-performance liquid and gas chromatography coupled with mass spectrometry. Multivariate statistical analyses were performed to select metabolites that contribute most to groups' classification (21 from liquid in both ionization modes and 9 from gas chromatography-mass spectrometry). We found metabolites related to energy imbalance, such as glycolysis-derived metabolites, as well as metabolites involved in fatty acid, lipid and amino acid metabolism. We observed statistically significant changes in threitol and aminomalonic acid in PAH patients, which could provide new biochemical insights into the pathogenesis of the disease. The results were externally validated on independent case and control cohorts, confirming up to 16 metabolites as statistically significant in the validation study. Multiplatform metabolomics, followed by multivariate chemometric data analysis has a huge potential for explaining pathogenesis of PAH and for searching potential and new more specific and less invasive markers of the disease

Three-Step Stacking by Field-Enhanced Sample Injection, Sweeping, and Micelle to Solvent Stacking in Capillary Electrophoresis: Anionic Analytes

Three-step stacking by field-enhanced sample injection (FESI), sweeping, and micelle to solvent stacking (MSS) in co-EOF capillary zone electrophoresis (CZE) is presented for anionic analytes. Long FESI produced an overloaded stacked zone of analytes (four model penicillins). Sweeping of the FESI zone was by electrokinetic injection of cetyltrimethylammonium bromide (CTAB) micelles. MSS was by short injection of 60% methanol that released the swept analytes from CTAB micelles. The sensitivity enhancement factors were 146–279 and 519–954 for conductivity ratio of 10 and 100, respectively. The SEF enhancement factors (factor = SEF from three-step stacking/SEF from FESI) were 16–32 and 6–10, correspondingly. The LODs were between 6.6–13.2 ng/mL, repeatability (intraday and interday) was %RSD ≤ 5.4%, and linearity was R2 ≥ 0.998. Application to real sample was investigated using fortified plasma after liquid–liquid extraction

POSTER :Optymalizacja transferu metody rozdzielania wybranych enancjomerów leków ß-adrenolitycznych z zastosowaniem elektroforezy kapilarnej

info:eu-repo/semantics/nonPublishe

Sustainability in drug discovery

Due to the expanding and ageing world population, the importance and use of medicines is expected to increase. However, this will lead to a greater impact on the ecosystem and our health in the long term. The concept of sustainability is rather slowly gaining traction and is currently still fragmented in the pharmaceutical field. A consortium of researchers from five European universities therefore advocates a global, systematic approach and places the emphasis on sustainability already in early stages of drug development, i.e. drug discovery. According to the researchers, the competent authorities, universities, research institutions and industrial organizations all need to take sustainability more into account. They summarized the most important opportunities on the basis of ten sustainability principles

New biochemical insights into the mechanisms of pulmonary arterial hypertension in humans

Diagnosis of pulmonary arterial hypertension (PAH) is difficult due to the lack of specific clinical symptoms and biomarkers, especially at early stages. We compared plasma metabolic fingerprints of PAH patients (n = 20) with matched healthy volunteers (n = 20) using, for the first time, untargeted multiplatform metabolomics approach consisting of high-performance liquid and gas chromatography coupled with mass spectrometry. Multivariate statistical analyses were performed to select metabolites that contribute most to groups' classification (21 from liquid in both ionization modes and 9 from gas chromatography-mass spectrometry). We found metabolites related to energy imbalance, such as glycolysis-derived metabolites, as well as metabolites involved in fatty acid, lipid and amino acid metabolism. We observed statistically significant changes in threitol and aminomalonic acid in PAH patients, which could provide new biochemical insights into the pathogenesis of the disease. The results were externally validated on independent case and control cohorts, confirming up to 16 metabolites as statistically significant in the validation study. Multiplatform metabolomics, followed by multivariate chemometric data analysis has a huge potential for explaining pathogenesis of PAH and for searching potential and new more specific and less invasive markers of the disease