The Effect of Conjugation with Octaarginine,a Cell-Penetrating Peptide on Antifungal Activity of Imidazoacridinone Derivative

Acridine cell-penetrating peptide conjugates are an extremely important family of compounds in antitumor chemotherapy. These conjugates are not so widely analysed in antimicrobial therapy, although bioactive peptides could be used as nanocarriers to smuggle antimicrobial compounds. An octaarginine conjugate of an imidazoacridinone derivative (Compound 1-R8) synthetized by us exhibited high antifungal activity against reference and fluconazole-resistant clinical strains (MICs ≤ 4 μg mL⁻¹). Our results clearly demonstrate the qualitative difference in accumulation of the mother compound and Compound 1-R8 conjugate into fungal cells. Only the latter was transported and accumulated effectively. Microscopic and flow cytometry analysis provide some evidence that the killing activity of Compound 1-R8 may be associated with a change in the permeability of the fungal cell membrane. The conjugate exhibited low cytotoxicity against human embryonic kidney (HEK-293) and human liver (HEPG2) cancer cell lines. Nevertheless, the selectivity index value of the conjugate for human pathogenic strains remained favourable and no hemolytic activity was observed. The inhibitory effect of the analysed compound on yeast topoisomerase II activity suggested its molecular target. In summary, conjugation with R8 effectively increased imidazoacridinone derivative ability to enter the fungal cell and achieve a concentration inside the cell that resulted in a high antifungal effect.     

Porphyrin Based 2D-MOF Structures as Dual-Kinetic Sorafenib Nanocarriers for Hepatoma Treatment

The existing clinical protocols of hepatoma treatment require improvement of drug efficacy that can be achieved by harnessing nanomedicine. Porphyrin-based, paddle-wheel framework (PPF) structures were obtained and tested as dual-kinetic Sorafenib (SOR) nanocarriers against hepatoma. We experimentally proved that sloughing of PPF structures combined with gradual dissolving are effective mechanisms for releasing the drug from the nanocarrier. By controlling the PPF degradation and size of adsorbed SOR deposits, we were able to augment SOR anticancer effects, both in vitro and in vivo, due to the dual kinetic behavior of SOR@PPF. Obtained drug delivery systems with slow and fast release of SOR influenced effectively, although in a different way, the cancer cells proliferation (reflected with EC50 and ERK 1/2 phosphorylation level). The in vivo studies proved that fast-released SOR@PPF reduces the tumor size considerably, while the slow-released SOR@PPF much better prevents from lymph nodes involvement and distant metastases.     

Diagnostic Utility of Genetic and Immunohistochemical H3-3A Mutation Analysis in Giant Cell Tumour of Bone

To validate the reliability and implementation of an objective diagnostic method for giant cell tumour of bone (GCTB). H3-3A gene mutation testing was performed using two different methods, Sanger sequencing and immunohistochemical (IHC) assays. A total of 214 patients, including 120 with GCTB and 94 with other giant cell-rich bone lesions, participated in the study. Sanger sequencing and IHC with anti-histone H3.3 G34W and G34V antibodies were performed on formalin-fixed, paraffin-embedded tissues, which were previously decalcified in EDTA if needed. The sensitivity and specificity of the molecular method was 100% (95% CI: 96.97–100%) and 100% (95% CI: 96.15–100%), respectively. The sensitivity and specificity of IHC was 94.32% (95% CI: 87.24–98.13%) and 100% (95% CI: 93.94–100.0%), respectively. P.G35 mutations were discovered in 2/9 (22.2%) secondary malignant GCTBs and 9/13 (69.2%) GCTB after denosumab treatment. We confirmed in a large series of patients that evaluation of H3-3A mutational status using direct sequencing is a reliable tool for diagnosing GCTB, and it should be incorporated into the diagnostic algorithm. Additionally, we discovered IHC can be used as a screening tool. Proper tissue processing and decalcification are necessary. The presence of the H3-3A mutation did not exclude malignant GCTB. Denosumab did not eradicate the neoplastic cell population of GCTB.     

Studies on iodine content in daily diets and selected dairy products

Poland's people have moderate – and in seaside areas mild – degrees of severity of iodine deficiency. A national program has been introduced for obligatory iodine prophylaxis and includes the iodination of household salt to the extent of 30 ±10 mg KI/kg. In order to assess the extent of iodine consumption, analytical studies were carried out on iodine content in average Polish diets. Taking into account the fact that milk formulae are frequently the basic source of iodine for infants, studies were performed on the iodine content in selected dairy products, mainly infant formulae. Iodine concentrations in samples were determined in duplicate by radioactive neutron activation analysis (RNAA). The iodine content in Polish diets without added iodinated kitchen salt was low and insufficient to provide the Polish RDA for this element. The results of the analytical investigations of the daily diets showed higher iodine content in comparison to theoretical calculations. The theoretical values accounted for 71–85% of the analytical ones. Study of iodine content in infant formula demonstrated differences between the analytically determined iodine content in products and that declared by producers. Received: 22 November 1999     

The Phenoxyalkyltriazine Antagonists for 5-HT6 Receptor with Promising Procognitive and Pharmacokinetic Properties In Vivo in Search for a Novel Therapeutic Approach to Dementia Diseases

Among the serotonin receptors, one of the most recently discovered 5-HT₆ subtype is an important protein target and its ligands may play a key role in the innovative treatment of cognitive disorders. However, none of its selective ligands have reached the pharmaceutical market yet. Recently, a new chemical class of potent 5-HT₆ receptor agents, the 1,3,5-triazine-piperazine derivatives, has been synthesized. Three members, the ortho and meta dichloro- (1,2) and the unsubstituted phenyl (3) derivatives, proved to be of special interest due to their high affinities (1,2) and selectivity (3) toward 5-HT₆ receptor. Thus, a broader pharmacological profile for 1–3, including comprehensive screening of the receptor selectivity and drug-like parameters in vitro as well as both, pharmacokinetic and pharmacodynamic properties in vivo, have been investigated within this study. A comprehensive analysis of the obtained results indicated significant procognitive-like activity together with beneficial drug-likeness in vitro and pharmacokinetics in vivo profiles for both, (RS)-4-[1-(2,3-dichlorophenoxy)propyl]-6-(4-methylpiperazin-1-yl)-1,3,5-triazin-2-amine (2) and (RS)-4-(4-methylpiperazin-1-yl)-6-(1-phenoxypropyl)-1,3,5-triazin-2-amine (3), but insensibly predominant for compound 2. Nevertheless, both compounds (2 and 3) seem to be good Central Nervous System drug candidates in search for novel therapeutic approach to dementia diseases, based on the 5-HT₆ receptor target.     

Antimicrobial and Cytotoxic Properties of Bisquaternary Ammonium Bromides of Different Spacer Length

A group of cationic gemini surfactants (bisquaternary ammonium bromides) with different spacer chain lengths (8–6–8, 8–7–8, 8–8–8, 8–9–8) was investigated, paying special attention to antimicrobial and the cytotoxic properties as well as their antimicrobial activity during long‐term storage. It was shown that the compounds investigated exhibit excellent antimicrobial activity against Gram‐positive bacteria (Staphylococcus aureus) and Gram‐negative bacteria (Pseudomonas aeruginosa) as well as antifungal properties (Candida albicans). The gemini surfactants tested had the differential level of cytotoxicity against normal lymphocytes. It was shown that the spacer chain length plays an important role in antibacterial activity and influences the cytotoxicity. The gemini surfactants with shorter spacer chain length, that had higher critical micelle concentration, showed generally weaker antibacterial properties, but on the other hand, these exhibited lower level of cytotoxicity. Furthermore, the aqueous solution of gemini surfactants exhibited the same antimicrobial activity even after 3 months.     

Thermal analysis of bulk carbon-carbon composite and friction products derived from it during simulated aircraft braking

Friction layer and friction debris samples obtained from commercially available carbon-carbon composite brake material (3D, C/C PAN CVI) by sub-scale dynamometer testing at 50% relative humidity and 100% normal aircraft landing energy have been characterized by multiple thermo-analytical techniques to investigate adsorption/desorption phenomena of physically bonded moisture and formation and decomposition of oxygen-containing structures. Thermogravimetric Analysis/Fourier Transform Infrared Spectroscopy, Temperature Programmed Reduction and Pyrolysis-Gas Chromatography-Mass Spectrometry experiments with friction layer and friction debris were accompanied with release of H₂O, CO₂ and CO on heating. These products are not observed when comparable analyses with the bulk brake material were performed. These data reflect significant oxidation of the original brake material and indicate that gaseous products (carbon oxides, H₂O) are released from the modified brake material during heating to temperatures approximating those experienced during typical aircraft braking.     

Block copolymer vesicles—using concepts from polymer chemistry to mimic biomembranes

Owing to the increasing interest in self-assembled structures from block copolymer materials, we present here a review of recent literature concerning amphiphilic block copolymer vesicles. A vesicular morphology is applicable not only in such fields like delivery-release and biomineralization, but also has been utilized for preparation of nanoreactors and incorporation of biological macromolecules.The organization of this paper is the following: we first provide the readers with the overview of the current literature concerning the vesicle preparation and most commonly used experimental methods applied for vesicle investigations. Next, we consider the vesicle formation in more detail and present the morphologies resulting from the interplay of factors influencing vesicular structures in solution. Further, membrane properties will be reviewed, and finally, we wish to focus on our group's achievements in studying nanocontainers from both ABA and ABC amphiphilic block copolymers.     

Principles for the evaluation of gas cavities in welded joints of steel on the basis of radiographs according to different European standards

During making a weld, many metallurgical reactions resulting from interaction between slag, gas and metal take place. These reactions influence the quality of welded joints. The oxidation, nitriding and hydriding phenomena occurring in welding processes can be a reason for gas void formation. Gas voids, which are the internal imperfections, are detected most often by radiographic methods. The purpose of this paper is to present the principles of assessment of gas cavities in welded joints, specified in different acceptance standards, on the basis of radiographic examination.     

Combined effects of inorganic constituents and pyrolysis conditions on the gasification reactivity of coal chars

A detailed phenomenological study of the gasification behavior of a North Dakota lignite was undertaken and the fundamental parameters that determine char reactivity were investigated. Differences in reactivity of up to three orders of magnitude were obtained by varying the conditions of coal pretreatment and pyrolysis. Pretreatment included demineralization with HCl and HF, ion exchange with ammonium acetate and back exchange with calcium acetate. Pyrolysis temperature, residence time and heating rate were varied in the range 975–1475 K, 0.3 s-1 h and 10 K/min-10⁴ K/s, respectively. The observed reactivity differences were rationalized in terms of variations in the concentration of carbon and catalyst active sites.