Paweł Góralski’s research while affiliated with University of Łódź and other places

In this paper, applying the density scaling idea to an associated liquid 4-methyl-2-pentanol used as an example, we identify different pressure-volume-temperature ranges within which molecular dynamics is dominated by either complex H-bonded networks most probably leading to supramolecular structures or non-specific intermolecular interactions like van der Waals forces. In this way, we show that the density scaling law for molecular dynamics near the glass transition provides a sensitive tool to detect thermodynamic regions characterized by intermolecular interactions of different type and complexity for a given material in the wide pressure-volume-temperature domain even if its typical form with constant scaling exponent is not obeyed. Moreover, we quantify the observed decoupling between dielectric and mechanical relaxations of the material in the density scaling regime. The suggested methods of analyses and their interpretations open new prospects for formulating models based on proper effective intermolecular potentials describing physicochemical phenomena near the glass transition.

The miscibility in the {1-propoxypropan-2-ol–water} system was investigated by differential scanning calorimetry. The specific heat capacities of 1-propoxypropan-2-ol aqueous solutions have been determined within the temperature range 274.15–338.15 K, over the wide concentration range by DSC. The apparent and partial molar heat capacities were calculated. Observed maxima on the concentration dependences of the partial molar heat capacities were interpreted as the result of aggregation taking place in the solution. Two-point scaling theory was used to analyze obtained results. Influence of the temperature on the values of critical indices were discussed in terms of possible structural changes in the solution. The mixing scheme was determined on the basis of the scanning calorimetry experiment.

Chronic lymphocytic leukemia (CLL) belongs to the group of hematological diseases with unknown etiology. The heterogeneity of disease could be caused by the diversities in cell signal transduction, epigenetic modifications and/or apoptosis inhibition. This type of leukemia mainly occurs older individuals, but in younger’s an aggressive form of the disease could lead to fast spectacular increase of leukemic cell numbers. In polish health system treatment options use for patient’s administration corresponding to international standards. Beside of that some patients still do not respond to anticancer therapy. It could happened that patient was administered for almost 6 months with drug(s) he is resistant to. Because of differences in clinical development of the disease and patient’s sensitivity to anti-cancer therapy, selecting an appropriate treatment approach for patients seems to be essential in optimizing the patient’s response to the used drug(s). Therefore, for many circumstances it is more easy to incubate leukemic cells with anticancer agents to find out the optimal in vitro patient’s cell response to the used drug(s) before its/their administration to patient. The aim of our studies was to compare the apoptotic induction potential based on individual patient’s sensitivity to drugs used in chronic lymphocytic leukemia treatment with expression of Bcr and Stat3 in CLL cells incubated with the combinations of cladribine (C) or fludarabine (F) with mafosfamide (CM, FM), or CM combined with rituximab (RCM) or roscovitine (Rosc), kinetin riboside (RK), rituximab alone (Rit) or rituximab with complement (Ritc). The obtained results by RT-PCR method revealed the differences in gene expression after CLL cell exposure to drugs/experimental agents, as well as in apoptosis induction potential. Personalized therapy analyses were performed using Vybrant Apoptosis Assay#4, differential scanning calorimetry and Western blot technique. The significant reduction of cell viability, increase of apoptosis rate and decrease or loss of thermal transition at 95±5°C in DSC profiles of nuclei isolated from CLL cells incubated with drugs/experimental compounds as well as PARP proteolytic cleavage were characteristic when treatment was effective. The obtained results show that drugs/experimental agents could imply on signal transduction and on apoptosis process realization.

Poster

The saturation heat capacities of eleven polyoxyethylene glycol monoalkyl ethers (CnEm) were measured by the calorimetric (DSC) method. The measurements were performed within the temperature range of (275.15 to 339.15) K by means of Micro DSCIII (Setaram) calorimeter. Assuming that the molar heat capacity (Cp,m) shows an additive character, the contributions to the Cp,m values of particular functional groups forming the compounds of CnEm series were calculated. Two models differing in the manner of molecule division into functional groups, i.e., first- and second-order additivity group contribution approach, were used. In the latter, not only the type of functional group but also its position and the closest neighborhood was taken into account. The average deviations between the experimental values of Cp and those estimated on the basis of the group contributions do not exceed 0.4 % for the compound of the series under investigation. The group contributions determined in this study make it possible to predict the molar heat capacity of monoethers CnEm within the temperature range of (270 to 350) K with an average error below 1 %.

The differential scanning calorimetry method (DSC) was used to examine the miscibility in the dipropylene glycol propyl ether (DPnP) + water system. Based on recorded curves of differential heat flow on temperature, HF , the range (composition, temperature) of the occurrence of miscibility gap, the values of lower critical solution temperature (LCST), and critical concentration were determined. On the basis of the experimentally determined specific heat capacity data the partial molar heat capacities () of DPnP in the mixtures with water were calculated. Analyzing changes in the course of function, the boundary of transition from a homogeneous solution was determined, in which the monomers of amphiphile dominate, to the region, in which aggregates of the cluster type appear.

To improve the efficacy of therapeutic options in chronic lymphocytic leukemia (CLL) an in vitro system to determine the response of mononuclear blood cells from blood of patients was elaborated. The study combines four approaches, i.e., cell viability, apoptosis rate, differential scanning calorimetry (DSC), and immunoblotting to develop personalized therapy protocols based on the cell sensitivity to drug exposure of individual CLL patients. The complementary analyses were performed on 28 peripheral blood samples from previously untreated CLL patients before therapy. The induction and progress of apoptosis in CLL cells exposed in vitro to purine analogs combined with mafosfamide, i.e., cladribine + mafosfamide (CM) and fludarabine + mafosfamide (FM) were assessed using the above approaches. The changes in thermal profiles (decrease/loss of transition at 95±5˚C) coincided with an accumulation of apoptotic cells, a decrease in the number of viable cells, and differences in the expression of the apoptosis‑related protein PARP‑1. No significant changes were observed in the thermal profiles of nuclei isolated from CLL cells resistant to the treatment. The complementary assays revealed a strong relationship between both the in vitro sensitivity of leukemia cells to drugs and the clinical response of the patients, determined usually after the sixth course of treatment (after ~6 months of therapy). As a summary of studies followed by complementary tests, our findings demonstrate the value of in vitro exposure of CLL cell samples to drugs intended to treat CLL patients, before their administration in order to recommend the most suitable and effective therapy for individual patients.