New Inhibitors of Bcr-Abl Based on 2,6,9-Trisubstituted Purine Scaffold Elicit Cytotoxicity in Chronic Myeloid Leukemia-Derived Cell Lines Sensitive and Resistant to TKIs.

Bcr-Abl is an oncoprotein with aberrant tyrosine kinase activity involved in the progression of chronic myeloid leukemia (CML) and has been targeted by inhibitors such as imatinib and nilotinib. However, despite their efficacy in the treatment of CML, a mechanism of resistance to these drugs associated with mutations in the kinase region has emerged. Therefore, in this work, we report the synthesis of 14 new 2,6,9-trisubstituted purines designed from our previous Bcr-Abl inhibitors.

Effect of Saccharides Coating on Antibacterial Potential and Drug Loading and Releasing Capability of Plasma Treated Polylactic Acid Films.

More than half of the hospital-associated infections worldwide are related to the adhesion of bacteria cells to biomedical devices and implants. To prevent these infections, it is crucial to modify biomaterial surfaces to develop the antibacterial property. In this study, chitosan (CS) and chondroitin sulfate (ChS) were chosen as antibacterial coating materials on polylactic acid (PLA) surfaces.

Plasma Mediated Chlorhexidine Immobilization onto Polylactic Acid Surface via Carbodiimide Chemistry: Antibacterial and Cytocompatibility Assessment.

The development of antibacterial materials has great importance in avoiding bacterial contamination and the risk of infection for implantable biomaterials. An antibacterial thin film coating on the surface via chemical bonding is a promising technique to keep native bulk material properties unchanged. However, most of the polymeric materials are chemically inert and highly hydrophobic, which makes chemical agent coating challenging Herein, immobilization of chlorhexidine, a broad-spectrum bactericidal cationic compound, onto the polylactic acid surface was performed in a multistep physicochemical method.

Slippery Liquid-Infused Porous Polymeric Surfaces Based on Natural Oil with Antimicrobial Effect.

Many polymer materials have found a wide variety of applications in biomedical industries due to their excellent mechanical properties. However, the infections associated with the biofilm formation represent serious problems resulting from the initial bacterial attachment on the polymeric surface. The development of novel slippery liquid-infused porous surfaces (SLIPSs) represents promising method for the biofilm formation prevention.

The association of a reduced susceptibility to moxifloxacin in causative Clostridium (Clostridioides) difficile strain with the clinical outcome of patients.

Objectives: To investigate the relationship between Clostridium (Clostridioides) difficile strain characteristics and C. difficile infection (CDI) outcome.

Methods: Between October and December 2017, 16 hospitals collected epidemiological data according to the European Centre for Disease Prevention and Control (ECDC) surveillance protocol for CDI.

Cryptic aberrations may allow more accurate prognostic classification of patients with myelodysplastic syndromes and clonal evolution.

The karyotype of bone-marrow cells at the time of diagnosis is one of the most important prognostic factors in patients with myelodysplastic syndromes (MDS). In some cases, the acquisition of additional genetic aberrations (clonal evolution [CE]) associated with clinical progression may occur during the disease. We analyzed a cohort of 469 MDS patients using a combination of molecular cytogenomic methods to identify cryptic aberrations and to assess their potential role in CE.

Preparation of Progressive Antibacterial LDPE Surface via Active Biomolecule Deposition Approach.

The use of polymers in all aspects of daily life is increasing considerably, so there is high demand for polymers with specific properties. Polymers with antibacterial properties are highly needed in the food and medical industries. Low-density polyethylene (LDPE) is widely used in various industries, especially in food packaging, because it has suitable mechanical and safety properties.

Antibacterial Activity and Cytotoxicity of Immobilized Glucosamine/Chondroitin Sulfate on Polylactic Acid Films.

Polylactic acid (PLA) is one of the most produced polymeric materials, due to its exceptional chemical and mechanical properties. Some of them, such as biodegradability and biocompatibility, make them attractive for biomedical applications. Conversely, the major drawback of PLA in the biomedical field is their vulnerability to bacterial contamination.

Antibacterial performance of ZnO-based fillers with mesoscale structured morphology in model medical PVC composites.

Three different ZnO-based antibacterial fillers having different morphologies in microscale region were prepared by the use of the microwave assisted synthesis protocol created in our laboratory with additional annealing in one case. Further, PVC composites containing 0.5-5 wt.

Minor C-geranylated flavanones from Paulownia tomentosa fruits with MRSA antibacterial activity.

Exhaustive chromatographic separation of the chloroform portion of the ethanolic extract obtained from Paulownia tomentosa (Thunb). Steud. (Paulowniaceae) fruits has led to isolation of ten C-6 geranylated flavanones tomentodiplacone C-I and mimulone C-E, featured by 3'-methoxy and 4'-hydroxy or 4'-hydroxy substitution of the B-ring of the flavonoid, respectively.

Antioxidative and EROD activities of osajin and pomiferin.

The major constituents of fruits of Maclura pomifera are the prenylated isoflavones, osajin (1) and pomiferin (2). Since significant biological activities of extracts from the wood of M. pomifera were previously reported, the peroxynitrite scavenging activity, inhibition of lipid peroxidation, scavenging of DPPH and EROD activity of these two major substances were studied.

[Natural substances as chemoprotective agents].

The fate of xenobiotics in the organism and their toxic or therapeutic influence have been under intensive investigation in recent years. The compounds are searched for which affect as preventive agents cancerogenesis and other disorders caused by procancerogens and pro-mutagens from the environment. The main focus is on the compounds able to modulate the activity of enzymes of the Ist and IInd phase of xenobiotic detoxication or compounds with antioxidative activity.

Dracophane, a metacyclophane derivative from the resin of Dracaena cinnabari Balf.

Dracophane, a novel structural derivative of metacyclophane, was isolated from the resin of Dracaena cinnabari Balf. The structure of this compound was determined by spectroscopic methods to be 3,12,21-trihydroxy-1,10,19-tris(4-hydroxyphenyl)-5,14,23-trimethoxy[3.3.

[Optic neuritis as the first sign of multiple sclerosis].

Background: Optic neuritis (ON) is as the initial manifestation of multiple sclerosis (SM) a favourable prognostic factor during the subsequent course.

Objective: To assess the ratio of ON at the onset of SM in the authors patients and to assess according to clinical criteria the form of disease and degree of functional inability, expressed by Kurtzke s EDSS scale.

Patients And Methods: In a retrospective analysis of patients with clinically defined and probable SM (Poser s criteria)) hospitalized at the neurological clinic in 1987-2000 the authors investigated the incidence of ON in relation to the course and form of SM.

Biological activities of oligoketide pigments of Monascus purpureus.

Rubropunctatin (1), monascorubrin (2), monascin (3) and ankaflavin (4) were purified from the mycelium of Monascus purpureus by flash chromatography on silica gel or reversed phase. Their embryotoxicity towards chicken embryos decreased in the order 2 > 1 > 3 > 4. The lower homologues 1 and 3 exhibited teratogenic effects on these organisms.

Separation of structurally related flavonoids by GC/MS technique and determination of their polarographic parameters and potential carcinogenicity.

The present study deals with the investigation of the naturally occurring derivatives of the benzo[b]pyran-4-one - flavonoids - chrysin, tectochrysin and galangin, and with the effect of minor changes in their chemical structure on their separation using GC/MS. In the relation to their close chemical structure, their basic polarographic parameters were also investigated. Their potential carcinogenicity index tg alpha was determined by DC polarography experiments in the presence of alpha-lipoic acid.

Genotoxicity and embryotoxicity of urban air particulate matter collected during winter and summer period in two different districts of the Czech Republic.

This study is the in vitro part of a long-term program to investigate the impact of air pollution on the health of a population in a polluted region of Northern Bohemia. In order to assess the possible health risks associated with a complex mixture of hundreds of organic compounds adsorbed to air particles, we used a biomarker-directed fractionation procedure to evaluate biological activities of different chemical compound classes. The extractable organic compounds from the air particles collected in both the polluted and the control districts during the summers and winters of 1993-1994 were investigated.

[Embryotoxic effects of a combination of zearalenone and vomitoxin (4-dioxynivalenole) on the chick embryo].

Mycotoxins zearalenone and vomitoxin (4-deoxynivalenol) are often joint contaminants of grains infested by micromycetes of the genus Fusarium. Toxic effects of both mycotoxins on experimental organisms and farm animals are well known, but we have not found any literary reference to toxic effects of the combination zearalenone and vomitoxin. Embryotoxic effects of zearalenone, vomitoxin and combinations of various doses of zearalenone with constant addition of vomitoxin were studied in a three-day chick embryo.

Embryotoxicity in chick embryo of thalidomide hydrolysis products following metabolic activation by rat liver homogenate.

Three and four-day-old chick embryos were exposed to thalidomide as well as to its hydrolysis products before and after in vitro biotrasformation of these compounds with rat liver homogenate. Significant embryotoxic effects of 30 and 100 micrograms doses per embryo encountered only in the case when the products of alkaline hydrolysis of thalidomide were pretreated with rat liver homogenate.

Monitoring genotoxic exposure in uranium mines.

Recent data from deep uranium mines in Czechoslovakia indicated that mines are exposed to other mutagenic factors in addition to radon daughter products. Mycotoxins were identified as a possible source of mutagens in these mines. Mycotoxins were examined in 38 samples from mines and in throat swabs taken from 116 miners and 78 controls.

Monitoring genotoxic exposure in uranium miners.

Recent data from deep uranium mines in Czechoslovakia indicated that in addition to radon daughter products, miners are also exposed to chemical mutagens. Mycotoxins were identified as a possible source of mutagenicity present in the mines. Various methods of biomonitoring were used to examine three groups of miners from different uranium mines.

Embryotoxicity of T-2 toxin and secalonic acid in embryonic chicks varies with the site of administration.

A crucial role of the site of administration in the sensitivity of the alternative system using chick embryo for testing embryotoxicity was demonstrated by morphological evaluation of the effects of T-2 toxin and secalonic acid D, and by incorporation of [14C]sodium acetate radioactivity. Secalonic acid D, administered to 2-, 3-, and 4-day-old embryos in doses higher than 1 microgram produced mostly malformations of the face (bilateral cleft beak, microphthalmia) while the teratogenic effects of T-2 toxin were being limited to the embryonic trunk of 2-day-old embryos (rumplessness) after administering doses higher than 0.001 microgram.

[Use of chick embryos for prediction of embryotoxic effects of mycotoxins in mammals].

Embryotoxic effects of 25 mycotoxins were investigated in two-, three- and four-day chick embryos; the results were evaluated on the eighth day of development. The embryotoxicity ranged from 0.0001 to 0.

The influence of DNA-topoisomerase II inhibitors novobiocin and fostriecin on the induction and repair of DNA damage in Chinese hamster ovary (CHO) cells treated with mitoxantrone.

Novobiocin (NB) at the concentration of 2 mmol/l added to the culture medium together with mitoxantrone (MIT) (0.05-0.2 micrograms/ml) reduced the number of MIT-induced single-strand breaks of DNA to approximately one half measured by alkaline DNA unwinding and hydroxyapatite chromatography of DNA and similarly it reduced also the fraction of DNA linked to proteins measured by the K(+) -SDS precipitation method.