The Levels of Cortisol and Selected Biochemical Parameters in Red Deer Harvested during Stalking Hunts.

As a reactive species, the red deer is sensitive to both negative exogenous and endogenous stimuli. An intensive hunting period may have a particularly negative impact on game animals. The aim of this study was to determine the plasma cortisol level and biochemical parameters in 25 wild red deer (Cervus elaphus) harvested during stalking hunts in correlation with the sex and age of the animals. The mean cortisol concentrations in the stags and hinds analyzed in this study were similar (20.2 and 21.5 ng/mL, respectively). Higher HDL cholesterol values were found in the blood of the hinds than in stags (p < 0.05). Similarly, the mean levels of LDL cholesterol, lactate dehydrogenase, and alanine aminotransferase were higher by 21%, 16%, and 42%, respectively, in the blood of the hinds. In contrast, the levels of alkaline phosphatase, bilirubin, and aspartate aminotransferase were higher in the stags (by 30%, 49%, and 36%, respectively). There was a negative correlation of the cortisol concentration with urea and bilirubin and a positive correlation between cortisol and aspartate aminotransferase in the stags (p < 0.05). In turn, a negative correlation was found between the cortisol and urea levels in the hinds (p < 0.05). In summary, the stress caused by stalking hunts and the characteristic behavior of red deer during the mating season had an impact on chosen biochemical parameters. The increased concentration of cortisol resulted in a decrease in the carcass mass, which may lead to the deterioration of the physical condition of animals on hunting grounds.

Investigation of the Affinity of Ceftobiprole for Selected Cyclodextrins Using Molecular Dynamics Simulations and HPLC.

This paper presents the theoretical calculations of the inclusion complex formation between native ceftobiprole, a promising antibiotic from the cephalosporin group, and selected cyclodextrins (CDs) approved by the European Medicines Agency. Ceftobiprole was studied in three protonation states predicted from pKa calculations, along with three selected CDs in a stoichiometric ratio of 1:1. It was introduced into the CD cavity in two opposite directions, resulting in 18 possible combinations. Docking studies determined the initial structures of the complexes, which then served as starting structures for molecular dynamics simulations. The analysis of the obtained trajectories included the spatial arrangement of ceftobiprole and CD, the hydrogen bonds forming between them, and the Gibbs free energy (ΔG) of the complex formation, which was calculated using the Generalised Born Surface Area (GBSA) equation. Among them, a complex of sulfobutyl ether- (SBE-) ß-CD with protonated ceftobiprole turned out to be the most stable (ΔG = -12.62 kcal/mol = -52.80 kJ/mol). Then, experimental studies showed changes in the physiochemical properties of the ceftobiprole in the presence of the CDs, thus confirming the validity of the theoretical results. High-performance liquid chromatography analysis showed that the addition of 10 mM SBE-ß-CD to a 1 mg/mL solution of ceftobiprole in 0.1 M of HCl increased the solubility 1.5-fold and decreased the degradation rate constant 2.5-fold.

Physiological response of roe deer (Capreolus capreolus) during stalking hunts depending on age.

BACKGROUND: The European roe deer (Capreolus capreolus) is a species particularly reactive to all kinds of negative stimuli. Hunting activity is one of the most potent stressors that disturbs the welfare of wild animals. During stress, various endocrine responses are elicited to improve the physical performance of the affected individual. A commonly assessed hormone for overcoming stressful situations is cortisol (CORT). In this study, plasma CORT levels in roe deer were assessed during the season of the most intense stalking hunts in Poland (summer vs. late autumn), the sex of the harvested animals (males vs. females), and age of harvest animal. In addition, the health status of the roe doe was evaluated on the basis of selected indices of blood chemistry, which could be associated with circulating cortisol levels. RESULTS: The mean cortisol levels were 58.066 ng/ml in the male group (summer) and 27.694 ng/ml in the female group (late autumn). Higher CORT levels were associated with a significantly lower of total cholesterol, lactate dehydrogenase, and uric acid (p < 0.05). Moreover, the mean concentration of uric acid was negatively correlated with the level of CORT in the male and female groups (p < 0.05). Together with the increase in mean CORT level, the HDL cholesterol of all the tested animals increased significantly (p < 0.05). CONCLUSIONS: Higher CORT in males during the summer than in females during the late autumn were most likely due to the arousal with the mating season. The level of CORT increased with the animals' age. Uric acid and age are both predictors of roe deer's serum CORT level.

Preliminary Studies on the Predation of the Mite Blattisocius mali (Acari: Blattisociidae) on Various Life Stages of Spider Mite, Thrips and Fruit Fly.

Research in recent years has shown that some species of predatory mites, considered to be typically associated with soil and litter, can also be found on plants. Such species include Blattisocius mali, which is an effective predator of acarid mites, nematodes and the eggs of moths and which can disperse by means of drosophilid fruit flies. Apart from soil and litter or storage, it has also been recorded on the bark of apple trees and the leaves of strawberries, thus suggesting its possible predation of/feeding on herbivorous mites and insects. Our goal was to examine whether B. mali could consume different development stages of two polyphagous herbivores, the two-spotted spider mite, Tetranychus urticae, and the western flower thrips, Frankliniella occidentalis, as well as the drosophilid fruit fly Drosophila hydei. In 24 h cage tests, single, starved B. mali females consumed all types of prey offered, i.e., the eggs, males and females of spider mites; the first-instar larvae and prepupae of thrips; and the eggs and first-instar larvae of fruit flies. The potential for B. mali to prey upon these insects and mites was confirmed. However, to estimate whether it can also effectively reduce their population, additional tests on the predator's survival, fecundity and prey preference are needed.

Ectoparasitism of the Flightless Drosophila melanogaster and D. hydei by the Mite Blattisocius mali (Acari: Blattisociidae).

Predatory mites dispersing by means of insects are often ectoparasites and may use various tactics to get onto the host, counteract its defenses, and diminish its survival. Blattisocius mali is a promising biological control agent which has been reported as transported by several drosophilid species. Our goal was to determine the type of relationship between this mite and fruit flies. We used flightless females of Drosophila melanogaster and D. hydei, which were commercially raised as live pet food. The predatory females mostly attacked the tarsi of the flies and then preferentially moved to the cervix or close to coxa III, where they eventually drilled their chelicerae and started feeding. Although both fly species used similar defensive tactics, more B. mali females did not attack D. hydei or did so with a delay, and a higher percentage of mites fell off the D. hydei tarsi during the first hour of observation. After 24 h, we noted the increased mortality of flies exposed to the presence of mites. Our study indicates the ectoparasitic relationship of B. mali with drosophilids. However, further research is needed to confirm the transport of this mite on wild D. hydei and D. melanogaster, both in the laboratory and under natural conditions.

Effects of the SLCO1B1 A388G single nucleotide polymorphism on the development, clinical parameters, treatment, and survival of multiple myeloma cases in a Polish population.

BACKGROUND: Multiple myeloma is one of the most common hematological malignancies worldwide. Genetic alterations may lead to the progression from monoclonal gammopathy to multiple myeloma. Additionally, the genetic background of the disease might influence therapy outcomes, including survival time. SLCO1B1, belonging to the OATPs family, is a membrane protein that mediates the uptake of a wide range of endogenous and exogenous (including drugs) compounds. METHODS AND RESULTS: In this study, the A388G single nucleotide polymorphism in the SLCO1B1 gene in Polish multiple myeloma patients was determined. This polymorphism affects the amino acid change of the protein, so it may be responsible for treatment effectiveness or risk of disease development. A388G was evaluated by the PCR-RFLP method. The presented study showed a statistically significant association between the GG genotype with longer survival of patients with multiple myeloma with Melphalan-Prednisone therapy compared to other treatment regimens (p = 0.0271). There was no statistically significant association in the frequency of genotypes (p = 0.8211) and alleles: allele A (p = 0.5442); allele G (p = 0.8020) between multiple myeloma patients and a control group. CONCLUSIONS: The A388G polymorphism does not seem to affect the increased risk of the development of multiple myeloma. However, the occurrence of the GG genotype may prolong of patients overall survival in the case of Melphalan-Prednisone therapy.

Study of Degradation Kinetics and Structural Analysis of Related Substances of Ceftobiprole by HPLC with UV and MS/MS Detection.

Ceftobiprole is a novel ß-lactam antibiotic, active against methicillin-resistant Staphylococcus aureus, vancomycin-resistant S. aureus and penicillin-resistant Streptococcus pneumoniae. To artificially generate potential degradation products (DPs) of ceftobiprole that may be formed under relevant storage conditions, acidic, alkaline, oxidative, photolytic and thermolytic stress tests were performed in both solution and solid state. A novel selective HPLC method was developed for the separation of ceftobiprole from its DPs and synthesis by-products (SBPs) using Kinetex Biphenyl column, ammonium acetate buffer pH 5.8 and acetonitrile. The kinetic studies demonstrated the low stability of ceftobiprole in alkaline solution, in the presence of an oxidising agent and under irradiation with near UV. In the solid state, ceftobiprole underwent oxidation when the powder was irradiated with visible light and UV. Based on mass spectroscopic analysis, 13 new structural formulas of SBPs and DPs were proposed, along with molecular formulas for three other DPs obtained in solution and four oxidative DPs characteristic of solid-state degradation.

Cyclodextrin Inclusion Complexes with Antibiotics and Antibacterial Agents as Drug-Delivery Systems-A Pharmaceutical Perspective.

Cyclodextrins (CDs) are a family of cyclic oligosaccharides, consisting of a macrocyclic ring of glucose subunits linked by α-1,4 glycosidic bonds. The shape of CD molecules is similar to a truncated cone with a hydrophobic inner cavity and a hydrophilic surface, which allows the formation of inclusion complexes with various molecules. This review article summarises over 200 reports published by the end of 2021 that discuss the complexation of CDs with antibiotics and antibacterial agents, including beta-lactams, tetracyclines, quinolones, macrolides, aminoglycosides, glycopeptides, polypeptides, nitroimidazoles, and oxazolidinones. The review focuses on drug-delivery applications such as improving solubility, modifying the drug-release profile, slowing down the degradation of the drug, improving biological membrane permeability, and enhancing antimicrobial activity. In addition to simple drug/CD combinations, ternary systems with additional auxiliary substances have been described, as well as more sophisticated drug-delivery systems including nanosponges, nanofibres, nanoparticles, microparticles, liposomes, hydrogels, and macromolecules. Depending on the desired properties of the drug product, an accelerated or prolonged dissolution profile can be achieved when combining CD with antibiotics or antimicrobial agents.

Changes in the expression of membrane type-matrix metalloproteinases genes (MMP14, MMP15, MMP16, MMP24) during treatment and their potential impact on the survival of patients with non-small cell lung cancer (NSCLC).

The analysis concerned the comparison of the expression of membrane type matrix metalloproteinases genes in the blood and tissue of NSCLC patients during the course of the disease and comparison to the control group. Blood and neoplastic tissue taken from 45 patients diagnosed with non-small cell lung cancer was a research material. The expression level of MMP14, MMP15, MMP16 and MMP24 was evaluated by qPCR and the results were compared with controls. The expression of MMP14 and MMP24 before tumor removal surgery and 100 days after was lower than in the control group. Interestingly, one year after surgery the levels of expression of these genes were identical to those in the control group. This suggests that the expression of metalloproteinase genes changes in the course of cancer and that effective treatment results in the normalization of gene expression. Lower expression of MMP15 in the blood of patients with more advanced cancer disease was observed, confirming the suppressive nature of changes in the blood. It has also been demonstrated that higher expression of MMP14 and MMP15 in the tissue is associated with more advanced stage of disease development or more invasive nature of the lesion. There is a noticeable increase of expression level in the environment surrounding the tumor, while a lower can be observed in the blood. This may indicate that changes in the expression of metalloproteinases in cancer are much more complex than merely the tumor tissue, which may also account for the inadequacies of metalloproteinase inhibitors.

What Could Arrest an Eriophyoid Mite on a Plant? The Case of Aculops allotrichus from the Black Locust Tree.

Aculops allotrichus is a vagrant eriophyoid that lives gregariously on the leaves of the black locust tree. This study demonstrated that conspecifics can have a significant impact on A. allotrichus females on unprofitable, old black locust leaves and can arrest them on those leaves. The effect was more pronounced in females that were exposed to artificially injured individuals than to intact ones. They not only prolonged their sojourn on leaf discs with pierced conspecifics, but also preferred the leaf disc halves with damaged individuals to clean ones. Aculops allotrichus is the first described herbivore in which artificially injured conspecifics, instead of causing alarm, keep the foraging individuals within a risky patch. Other objects, such as artificially injured or intact heterospecifics, pollen or sand, were irrelevant to the eriophyoid females on old leaf patches. In tests with old leaves of maple, magnolia and hard kiwi vine, the females postponed their movement from non-host leaf discs, which suggests that they may need more time to recognise and evaluate unfamiliar plants than familiar ones.

Synthesis of Oxidized 3ß,3'ß-Disteryl Ethers and Search after High-Temperature Treatment of Sterol-Rich Samples.

It was proven that sterols subjected to high-temperature treatment can be concatenated, which results in polymeric structures, e.g., 3ß,3'ß-disteryl ethers. However, it was also proven that due to increased temperature in oxygen-containing conditions, sterols can undergo various oxidation reactions. This study aimed to prove the existence and perform quantitative analysis of oxidized 3ß,3'ß-disteryl ethers, which could form during high-temperature treatment of sterol-rich samples. Samples were heated at 180, 200 and 220 °C for 0.5 to 4 h. Quantitative analyses of the oxidized 3ß,3'ß-disteryl ethers were performed with liquid extraction, solid-phase extraction and liquid chromatography coupled with mass spectrometry. Additionally, to perform this analysis, the appropriate standards of all oxidized 3ß,3'ß-disteryl ethers were prepared. Eighteen various oxidized 3ß,3'ß-disteryl ethers (derivatives of 3ß,3'ß-dicholesteryl ether, 3ß,3'ß-disitosteryl ether and 3ß,3'ß-distigmasteryl ether) were prepared. Additionally, the influence of metal compounds on the mechanism of ether formation at high temperatures was investigated.

Comprehensive Characterisation of the Ketoprofen-ß-Cyclodextrin Inclusion Complex Using X-ray Techniques and NMR Spectroscopy.

Racemic ketoprofen (KP) and ß-cyclodextrin (ß-CD) powder samples from co-precipitation (1), evaporation (2), and heating-under-reflux (3) were analysed using X-ray techniques and nuclear magnetic resonance (NMR) spectroscopy. On the basis of NMR studies carried out in an aqueous solution, it was found that in the samples obtained by methods 1 and 2, there were large excesses of ß-CD in relation to KP, 10 and 75 times, respectively, while the sample obtained by method 3 contained equimolar amounts of ß-CD and KP. NMR results indicated that KP/ß-CD inclusion complexes were formed and the estimated binding constants were approximately 2400 M-1, showing that KP is quite strongly associated with ß-CD. On the other hand, the X-ray single-crystal technique in the solid state revealed that the (S)-KP/ß-CD inclusion complex with a stoichiometry of 2:2 was obtained as a result of heating-under-reflux, for which the crystal and molecular structure were examined. Among the methods used for the preparation of the KP/ß-CD complex, only method 3 is suitable.

Explanation of the Formation of Complexes between Representatives of Oxazolidinones and HDAS-ß-CD Using Molecular Modeling as a Complementary Technique to cEKC and NMR.

Molecular modeling (MM) results for tedizolid and radezolid with heptakis-(2,3-diacetyl-6-sulfo)-ß-cyclodextrin (HDAS-ß-CD) are presented and compared with the results previously obtained for linezolid and sutezolid. The mechanism of interaction of chiral oxazolidinone ligands belonging to a new class of antibacterial agents, such as linezolid, tedizolid, radezolid, and sutezolid, with HDAS-ß-CD based on capillary electrokinetic chromatography (cEKC), nuclear magnetic resonance (NMR) spectroscopy, and MM methods was described. Principles of chiral separation of oxazolidinone analogues using charged single isomer derivatives of cyclodextrin by the cEKC method were presented, including the selection of the optimal chiral selector and separation conditions, complex stoichiometry, and binding constants, which provided a comprehensive basis for MM studies. In turn, NMR provided, where possible, direct information on the geometry of the inclusion complexes and also provided the necessary structural information to validate the MM calculations. Consequently, MM contributed to the understanding of the structure of diastereomeric complexes, the thermodynamics of complexation, and the visualization of their structures. The most probable mean geometries of the studied supramolecular complexes and their dynamics (geometry changes over time) were determined by molecular dynamics methods. Oxazolidinone ligands have been shown to complex mainly the inner part of cyclodextrin, while the external binding is less privileged, which is consistent with the conclusions of the NMR studies. Enthalpy values of binding of complexes were calculated using long-term molecular dynamics in explicit water as well as using molecular mechanics, the Poisson-Boltzmann or generalized Born, and surface area continuum solvation (MM/PBSA and MM/GBSA) methods. Computational methods predicted the effect of changes in pH and composition of the solution on the strength and complexation process, and it adapted the conditions selected as optimal during the cEKC study. By changing the dielectric constant in the MM/PBSA and MM/GBSA calculations, the effect of changing the solution to methanol/acetonitrile was investigated. A fairly successful attempt was made to predict the chiral separation of the oxazolidinones using the modified cyclodextrin by computational methods.

Importance of Altered Gene Expression of Metalloproteinases 2, 9, and 16 in Acute Myeloid Leukemia: Preliminary Study.

Acute myeloid leukemia is a group of hematological neoplasms characterized by a heterogeneous course and high mortality. The important factor in the neoplastic process is metalloproteinases, proteolytic enzymes capable of degrading various components of the extracellular matrix, which take an active part in modifying the functioning of the cell, including transformation to cancer cell. They interact with numerous signaling pathways responsible for the process of cell growth, proliferation, or apoptosis. In the present study, changes in the expression of MMP2, MMP9, and MMP16 genes between patients with AML and people without cancer were examined. The impact of cytogenetic changes in neoplastic cells on the expression level of MMP2, MMP9, and MMP16 was also assessed, as well as the impact of the altered expression on the effectiveness of the first cycle of remission-inducing therapy. To evaluate the expression of all studied genes MMP2, MMP9, and MMP16, SYBR Green-based real-time PCR method was used; the reference gene was GAPDH. For two investigated genes MMP2 and MMP16, the lower expression level was observed in patients with AML when compared to healthy people. The MMP9 gene expression level did not differ between patients with AML and healthy individuals which may indicate a different regulation of gene expression in acute myeloid leukemia. However, no correlation was observed between the genes' expression of all tested metalloproteinases and the result of cytoreductive treatment or the presence of cytogenetic changes. The obtained results show that the expression of MMP2 and MMP16 genes is reduced while the expression of MMP9 is unchanged in patients with acute myeloid leukemia. This may indicate a different regulation of the expression of these genes, and possible disruptions in gene transcription or posttranscriptional mechanisms in the MMP2 and MMP16 genes, however, do not affect the level of MMP9 expression. Obtained results in AML patients are in contrary to various types of solid tumors where increased expression is usually observed.

Clinical significance of HRAS and KRAS genes expression in patients with non-small-cell lung cancer - preliminary findings.

BACKGROUND: The RAS family protooncogenes, including KRAS, NRAS and HRAS, encode proteins responsible for the regulation of growth, differentiation and survival of many cell types. The HRAS and KRAS oncogene mutations are well defined, however, the clinical significance of RAS expressions in non-small-cell lung cancer (NSCLC) is still uncertain. METHODS: A total of 39 whole blood samples of NSCLC (the investigated group), collected at three points of time: at the time of diagnosis, 100 days and 1 year after the surgery as well as 35 tissue samples obtained during the surgery were included in this study. HRAS and KRAS genes mRNA expression were assessed using quantitative real-time polymerase chain reaction techniques. RESULTS: Increased relative HRAS mRNA level in blood was found significantly more frequently in the group of smokers (p = 0.008). Patients with squamous cell carcinoma subtypes of NSCLC were more likely to show an overexpression of HRAS gene in blood, but not statistically significant (p = 0.065). In tumor tissue overexpression of HRAS gene was associated with adenocarcinoma subtype (p = 0.049). No statistically significant associations were found for the expression of KRAS with any clinicopathological parameters, except the age of patients, within the study. There were no differences between the relative HRAS and KRAS genes expression levels in blood samples taken from the same patients during the 3 observation points, as well as between blood collected from patients before surgery and tissue samples obtained during operation. CONCLUSION: The potential associations between high HRAS expression levels, age, smoking status and histological type of cancer were observed, which emphasizes the need for further study of the RAS family. Therefore, subsequent research involving larger numbers of patients and a longer follow-up, as well as multicenter study are necessary to confirm our findings.

Assessment of the Role of Selected SMAD3 and SMAD4 Genes Polymorphisms in the Development of Colorectal Cancer: Preliminary Research.

BACKGROUND: Colon cancer is one of the most common types of malignant tumor worldwide. The molecular mechanism of colorectal carcinogenesis is very complex and not yet fully understood. The TGFß (transforming growth factor ß) signaling pathway plays a significant role in the development of many cancers, including colorectal cancer pathogenesis. Changes in TGFß pathway are associated with increased colorectal cancer risk, because this pathway participates in the control of important cellular processes such as cell growth, proliferation, differentiation, or apoptosis. The family of SMAD (similar to mother against decapentaplegic) proteins is closely correlated to this pathway. SMADs genes expression affects modulation of the transcription of many genes, which leads to the inhibition of cell-growth and apoptosis in colon epithelial cells. The presence of SNPs (single nucleotide polymorphisms) in SMADs genes encoding proteins involved in the control of biological processes important for the cell may play a significant role in the predisposition to the development of colorectal cancer, or in the regulation of the severity of changes related to tumor growth. Extension of data in this field may provide clinically significant conclusions influencing the implementation of personalized treatment based on specific changes characteristic of a patient with colorectal cancer. PURPOSE: The subject of this research was genotyping polymorphisms of SMAD3 (rs6494629) and SMAD4 (rs10502913, rs12968012, rs1057520801) genes in the group of patients with colorectal cancer and in the control group, and comparing the genotypic frequency distributions with clinical-pathological features within the study group and between the groups. MATERIALS AND METHODS: SNP genotyping analysis was performed on genomic DNA isolated from 84 frozen tissue sections of colorectal cancer and from 60 peripheral blood samples of patients without cancer. To evaluate the polymorphic variants of SMAD genes, the restricted fragment length of a polymorphism reaction (PCR-RFLP) was used. RESULTS: The results obtained in the study showed no significant association between the examined polymorphisms and the risk of developing colorectal cancer. CONCLUSION: More extensive studies to confirm the results obtained in this study are needed. Further studies on a larger study group divided according to the clinical stage and histological differentiation may allow finding or excluding the significance of the studied SNPs as potential markers of colorectal cancer in relation to the clinico-pathological data.

The solution and solid-state degradation study followed by identification of tedizolid related compounds in medicinal product by high performance liquid chromatography with diode array and tandem mass spectrometry detection.

The aim of the study was to investigate the intrinsic stability and to identify potential degradation products of tedizolid disodium phosphate (TED-OPO3Na2), which belongs to the antimicrobial agents of the oxazolidinone class. Tedizolid, as disodium phosphate (prodrug), is registered under the trade name SIVEXTRO®, at a dose of 200 mg, in the form of powder for injection or infusion. The stability-indicating assay method was optimised using HPLC with diode array detection and with electrospray ionisation time-of-flight mass spectrometry. In solution-state studies, the forced decomposition of TED-OPO3Na2 carried out under acidic, basic, oxidative, photocatalytic, and thermal conditions revealed the lability of TED-OPO3Na2 to acidic, basic, and photocatalytic (UV) conditions, while it was relatively stable in oxidative conditions and during thermolysis processes. The kinetics of degradation and shelf-life values in solution-state studies were determined, and activation energies were calculated for alkaline and thermolytic degradation. In contrast, in the solid state degradation study, TED-OPO3Na2 was stable under thermal conditions at high humidity and in visible light, while moderate degradation was observed under thermal conditions of low humidity and ultraviolet light. The developed method enabled the identification of 12 new degradation products and 3 new by-products.

Tedizolid-Cyclodextrin System as Delayed-Release Drug Delivery with Antibacterial Activity.

Progressive increase in bacterial resistance has caused an urgent need to introduce new antibiotics, one of them being oxazolidinones with their representative tedizolid. Despite the broad spectrum of activity of the parent tedizolid, it is characterized by low water solubility, which limits its use. The combination of the active molecule with a multifunctional excipient, which is cyclodextrins, allows preservation of its pharmacological activity and modification of its physicochemical properties. Therefore, the aim of the study was to change the dissolution rate and permeability through the model membrane of tedizolid by formation of solid dispersions with a cyclodextrin. The research included identification of tedizolid-hydroxypropyl-ß-cyclodextrin (tedizolid/HP-ß-CD) inclusion complex by thermal method (Differential Scanning Colorimetry), spectroscopic methods (powder X-ray diffraction, Fourier-Transform Infrared spectroscopy), and molecular docking. The second part of the research concerned the physicochemical properties (dissolution and permeability) and the biological properties of the system in terms of its microbiological activity. An increase in the dissolution rate was observed in the presence of cyclodextrin, while maintaining a high permeation coefficient and high microbiological activity. The proposed approach is an opportunity to develop drug delivery systems used in the treatment of resistant bacterial infections, in which, in addition to modifying the physicochemical properties caused by cyclodextrin, we observe a favorable change in the pharmacological potential of the bioactives.

Accumulation of Toxic Elements in Bone and Bone Marrow of Deer Living in Various Ecosystems. A Case Study of Farmed and Wild-Living Deer.

The aim of the study was to determine the concentrations of toxic elements accumulated in the bone marrow and bones (Cervus elaphus). The studies were carried out on two groups of young stags: farmed (n = 6) and wild (n = 9). Their body weights were measured and bone and bone marrow samples were collected. The concentrations of toxic elements were analyzed using the inductively coupled plasma mass spectrometry technique. The mean aluminum content in the bone marrow and bones of the farmed animals was significantly higher than in the wild group (p < 0.05). The mean concentration of arsenic, barium and lead in the bones of the wild red deer was significantly higher than in the bones of the farmed animals (p < 0.05), while the cadmium concentration in the bones of the farmed red deer exceeded the value determined in the wild animals. A significant difference was found between the mean concentrations of aluminum, arsenic, barium, lead, vanadium and nickel in the bone marrow and bones of both red deer groups (p < 0.05). Although the study involved animals living in an uncontaminated area, the concentrations of some heavy metals were higher than values reported from industrial regions.

The impact of ABCB1 gene polymorphism and its expression on non-small-cell lung cancer development, progression and therapy - preliminary report.

The ABCB1 gene belongs to ATP binding cassette (ABC) transporter genes that has been previously implicated in cancer progression and drug response. This study aimed to evaluate the association between the SNP 3435 and the expression of the ABCB1 gene in lung cancer patients in the Polish population in comparison to clinicopathological parameters and treatment. 150 RNA and 47 DNA samples were isolated from 49 lung cancer cases including both tissue samples and blood taken from the same patients at three time points: diagnosis, 100 days and one year after the surgical intervention. Qualitative and real-time PCR analysis of expression were done, also genotyping by PCR-RFLP. Mutant homozygous TT and allele T are present statistically significantly more frequently in the group of patients with lung cancer. There is no difference with expression level in lung cancer tissue and blood sample taken from the same patients before surgical treatment. On the basis of blood samples analysis it was observed that the expression level of ABCB1 mRNA was growing in time. Higher levels were marked after 100 days and one year after the surgical intervention. The complementary pharmacological treatment induced higher expression levels of ABCB1. The presented data suggest an important role of ABCB1 in lung cancer, the increasing level of ABCB1 mRNA which can be connected with induction of multidrug resistance mechanism is also significant, that observation must be confirmed in further analysis.