Marta Kordalewska

The incidence of bladder cancer (BCa) has remained high for many years. Nevertheless, its pathomechanism has not yet been fully understood and is still being studied. Therefore, multiplatform untargeted urinary metabolomics analysis has been performed in order to study differences in the metabolic profiles of urine samples collected at three time points: before transurethral resection of bladder tumor (TURBT), the day after the procedure and two weeks after TURBT. Collected samples were analyzed with the use of high-performance liquid chromatography hyphenated with time-of-flight mass spectrometry detection (HPLC-TOF/MS) and gas chromatography coupled with triple quadrupole mass spectrometry detection (GC-QqQ/MS, in a scan mode). Levels of metabolites selected in our previous study were assessed in order to confirm their potential to differentiate the healthy and diseased samples, regardless of the risk factors and individual characteristics. Hippuric acid, pentanedioic acid and uridine confirmed their potential for sample differentiation. Based on the results of statistical analysis for the paired samples (comparison of metabolic profiles of samples collected before TURBT and two weeks after), a set of metabolites belonging to nucleotide metabolism and methylation processes was also selected. Longitudinal studies proved to be useful for the evaluation of metabolic changes in bladder cancer.

Background: Resistant hypertension (RH) affects about 15-20% of treated hypertensive patients worldwide. RH increases the risk of cardiovascular events such as myocardial infarction and stroke by 50%. The pathological mechanisms underlying resistance to treatment are still poorly understood. Objective: The main goal of this pilot study was to determine and compare plasma metabolomic profiles in resistant and non-resistant hypertensive patients. Methods: We applied untargeted metabolomic profiling in plasma samples collected from 69 subjects with RH and 81 subjects with controlled hypertension. To confirm patients’ compliance to antihypertensive treatment, levels of selected drugs and their metabolites were determined in plasma samples with the LC-ESI-TOF/MS technique. Results: The results showed no statistically significant differences in the administration of antihypertensive drug in the compared groups. We identified 19 up-regulated and 13 downregulated metabolites in the RH. Conclusion: The metabolites altered in RH are linked to oxidative stress and inflammation, endothelium dysfunction, vasoconstriction and cell proliferation. Our results may generate new hypothesis about RH development and progression.

Aim: The purpose of this work was to develop and validate a rapid and robust LC–MS/MS method for the determination of dexmedetomidine (DEX) in plasma, suitable for analysis of a large number of samples. Method: Systematic approach, Design of Experiments, was applied to optimize ESI source parameters and to evaluate method robustness, therefore, a rapid, stable and cost-effective assay was developed. The method was validated according to US FDA guidelines. LLOQ was determined at 5 pg/ml. The assay was linear over the examined concentration range (5–2500 pg/ml), Results: Experimental design approach was applied for optimization of ESI source parameters and evaluation of method robustness. The method was validated according to the US FDA guidelines. LLOQ was determined at 5 pg/ml. The assay was linear over the examined concentration range (R2 > 0.98). The accuracies, intra- and interday precisions were less than 15%. The stability data confirmed reliable behavior of DEX under tested conditions. Conclusion: A...