Gdańsk Medical University

About: Gdańsk Medical University is a education organization based out in Gdańsk, Poland. It is known for research contribution in the topics: Population & Cancer. The organization has 4893 authors who have published 11216 publications receiving 260523 citations.

Peroxisome proliferator-activated receptor alpha is downregulated in the failing human heart

Abstract: Cardiac hypertrophy in humans is associated with a decrease in myocardial fatty acid beta-oxidation (FAO) and accompanying alterations in metabolic gene expression. Flux through the cardiac FAO pathway, which is the principal source of energy production in the adult mammalian heart, is tightly controlled in accordance with energy demands. In rodents, the FAO pathway is under control of a nuclear peroxisome proliferator-activated receptor alpha (PPARalpha?. We sought to delineate the molecular regulatory events involved in the energy substrate preference switch from fatty acids to glucose during cardiac hypertrophic growth in humans. We analysed the amount of PPARalpha protein in human cardiac tissue. PPARalpha protein level was measured in homogenates prepared from left ventricular biopsies taken from five control donor hearts and compared to the amount of this transcription factor in biopsies from five patients with compensated end-stage heart failure (HF) at the time of transplantation. Using Western blot analysis with a monoclonal antibody against human PPARalpha, we observed a significant decrease (54%) in the mean amount of PPARalpha in the group of HF patients compared to that in the donor tissue. This study indicates that the decrease in cardiac PPARalpha transcription factor gene expression observed in the failing human heart could play an important role in a reduction in fatty acid utilisation by the adult heart during cardiac hypertrophy.

Determination of pKa by pH gradient reversed-phase HPLC.

Abstract: pH gradient reversed-phase HPLC consists of a programmed increase during the chromatographic run of the eluting power of the mobile phase with regard to ionizable analytes. On the analogy of the conventional organic modifier gradient RP HPLC, in the pH gradient mode, the eluting strength of the mobile phase increases due to its increasing (with acid analytes) or decreasing (with basic analytes) pH, whereas the content of organic modifier is kept constant. We have shown previously that the pH gradient separations are technically possible using standard chromatographic equipment. Here we demonstrate that the method is uniquely suitable to determine pKa values of analytes. A strict theoretical model is proposed to determine pKa values based on the retention data from a pH gradient RP HPLC run. The pKa data so obtained are discussed in relation to the concentration of methanol in the mobile phase, the type of stationary phase, and the duration of the gradient. The pKa values determined by the pH gradient meth...

Prediction of peptide retention at different HPLC conditions from multiple linear regression models.

Abstract: To quantitatively characterize the structure of a peptide and to predict its gradient retention time at given HPLC conditions three structural descriptors are used: (i) logarithm of the sum of retention times of the amino acids composing the peptide, log SumAA, (ii) logarithm of the van der Waals volume of the peptide, log VDW(Vol), (iii) and the logarithm of the peptide's calculated n-octanol-water partition coefficient, clog P. The log SumAA descriptor is obtained from empirical data for 20 natural amino acids, determined in a given HPLC system. The two other descriptors are calculated from the peptides' structural formulas using molecular modeling methods. The quantitative structure-retention relationships (QSRR), build by multiple linear regression, describe HPLC retention of peptide on a given chromatographic system on which the retention of the 20 amino acids was predetermined. A structurally diversified series of 98 peptides was employed. The predicted gradient retention times on several chromatographic systems were in good agreement with the experimental data. The QSRR equations, derived for a given system operated at variable gradient times and temperatures allowed for the prediction of peptide retention in that system. Matching the experimental HPLC retention to the theoretically predicted for a presumed peptide could facilitate original protein identification in proteomics. In conjunction with MS data, prediction of the retention time for a given peptide might be used to improve the confidence of peptide identifications and to increase the number of correctly identified peptides.