ADME-Tox profiling of some low molecular weight water soluble chitosan derivatives

Within this study we use a few computational tools for predicting absorption, distribution, metabolism, excretion and toxicity (ADME-Tox), pharmacokinetics profiles, toxic/adverse effects, carcinogenicity, cardiotoxicity and endocrine disruption of some of low molecular weight water soluble derivatives of chitosan that are used in wound healing. Investigated compounds do not possess drug-like properties, their pharmacokinetics profiles reveal poor gastrointestinal absorption and low skin penetration. Chitosan derivatives cannot pass the blood-brain barrier and they are not able to inhibit the enzymes of the cytochrome P450 that are involved in the metabolism of xenobiotics. They do not reflect carcinogenicity and cardiotoxicity and reveal only a low probability to be endocrine disruptors. The main side effects in humans of the investigated compounds are: weight loss, acidosis, gastrointestinal toxicity, respiratory failure. This information is especially important for professional exposure and accidental contamination with these compounds

Supplementary data for the article: Menghiu, G.; Ostafe, V.; Prodanović, R.; Fischer, R.; Ostafe, R. A High-Throughput Screening System Based on Fluorescence-Activated Cell Sorting for the Directed Evolution of Chitinase A. International Journal of Molecular Sciences 2021, 22 (6), 3041. https://doi.org/10.3390/ijms22063041.

Supplementary material: [https://doi.org/10.3390/ijms22063041]Related to published version: [https://cherry.chem.bg.ac.rs/handle/123456789/4393

Assessment of nicotine for second hand smoke exposure in some public places in Romania by UPLC-MS

BACKGROUND: Air nicotine monitoring is a well-known procedure for estimation of exposure to second hand smoke. Few research studies were realized in Romania to evaluate environmental tobacco smoke (ETS) exposure of humans in different public places. The levels of airborne nicotine from environmental tobacco smoke and urinary cotinine and nicotine levels of some subjects were analyzed. In order to better implement/enforce the European legislation regarding the interdiction of smoking in the public places the national authorities need a rapid and reliable analytical method to quickly asses the state of the pollution with cigarette smoke of these populated areas. RESULTS: The nicotine concentration in the air from different types of public buildings was determined. The median concentration of nicotine in the air from 32 pubs where the smoking was allowed was 590 ng · L(-1), comparing with the pubs where the smoking was not permitted (22 locations) where the median concentration of nicotine was only 32 ng · L(-1). Similarly, the median concentration of nicotine in restaurants where the smoking was allowed (23 locations) was 510 ng · L(-1), in comparison with the restaurants where the smoking was prohibited (11 places) where the median value was 19 ng · L(-1). The lowest concentrations of nicotine were found in high schools (8 locations, median concentration 7.4 ng · L(-1)), universities (5 locations, 23 ng · L(-1)) and hospitals (6 locations, 16 ng · L(-1)). CONCLUSIONS: The method was validated and gave good linearity, precision, accuracy and limit of detection. The buildings included hospitals, high schools, universities, pubs and restaurants. The presence of air nicotine was recorded in all buildings studied. The highest median levels of air nicotine were found in pubs and restaurants. The presence of air nicotine in indoor public buildings indicates weak implementation of the smoke free law in Romania

Chitosan as a wound dressing starting material: antimicrobial Properties and mode of action

Fighting bacterial resistance is one of the concerns in modern days, as antibiotics remain the main resource of bacterial control. Data shows that for every antibiotic developed, there is a microorganism that becomes resistant to it. Natural polymers, as the source of antibacterial agents, offer a new way to fight bacterial infection. The advantage over conventional synthetic antibiotics is that natural antimicrobial agents are biocompatible, non-toxic, and inexpensive. Chitosan is one of the natural polymers that represent a very promising source for the development of antimicrobial agents. In addition, chitosan is biodegradable, non-toxic, and most importantly, promotes wound healing, features that makes it suitable as a starting material for wound dressings. This paper reviews the antimicrobial properties of chitosan and describes the mechanisms of action toward microbial cells as well as the interactions with mammalian cells in terms of wound healing process. Finally, the applications of chitosan as a wound-dressing material are discussed along with the current status of chitosan-based wound dressings existing on the market.publishedVersio

Spectral SAR Ecotoxicology of Ionic Liquids: The Daphnia magna

Aiming to provide a unified theory of ionic liquids ecotoxicity, the recent spectral structure activity relationship (S-SAR) algorithm is employed for testing the two additive models of anionic-cationic interaction containing ionic liquid activity: the causal and the endpoint, |0+〉 and |1+〉 models, respectively. As a working system, the Daphnia magna ecotoxicity was characterized through the formulated and applied spectral chemical-ecobiological interaction principles. Specific anionic-cationic-ionic-liquid rules of interaction along the developed mechanistic hypersurface map of the main ecotoxicity paths together with the so-called resonance limitation of the standard statistical correlation analysis were revealed

Determination of methylparaben from cosmetic products by ultra performance liquid chromatography

A new method for the determination of methylparaben by ultra-performance liquid chromatography (UPLC) was developed. Methylparaben is often used as preservative, alone or in combination with other parabens, being added to cosmetic products, pharmaceutical products and foods to avoid microbial contamination. Due to its widespread use and potential risk to human health, assessing human exposure to this compound is of interest. A good determination and quantification of methylparaben was developed with a gradient elution using a mixture of methanol and water (60:40, v/v) within 1.455 min. Under optimized conditions, the linear working range extends over two orders of magnitude with relative standard deviations of intra- and inter-day precision below 2.3 %, and a detection limit of 0.02 ng μL-1 for methylparaben. The proposed method was successfully applied to the assay of methylparaben in cosmetic products with minimal sample preparation

Solubility and ADMET profiles of short oligomers of lactic acid

Polylactic acid (PLA) is a polymer with an increased potential to be used in different medical applications, including tissue engineering and drug-carries. The use of PLA in medical applications implies the evaluation of the human organism\u27s response to the polymer inserting and to its degradation products. Consequently, within this study, we have investigated the solubility and ADMET profiles of the short oligomers (having the molecular weight lower than 3000 Da) resulting in degradation products of PLA. There is a linear decrease of the molar solubility of investigated oligomers with molecular weight. The results that are obtained also reveal that short oligomers of PLA have promising pharmacological profiles and limited toxicological effects on humans. These oligomers are predicted as potential inhibitors of the organic anion transporting peptides OATP1B1 and OATP1B3, they present minor probability to affect the androgen and glucocorticoid receptors, have a weak potential of hepatotoxicity, and may produce eye injuries. These outcomes may be used to guide or to supplement in vitro and/or in vivo toxicity tests such as to enhance the biodegradation properties of the biopolymer.</p

Non-conventional expression of recombinant chitinase A originating from Bacillus licheniformis DSM8785, in Saccharomyces cerevisiae INVSc1: Scientific paper

Chitinases are glycosyl hydrolases, that cleave the β-1,4 linkage between N-acetyl glucosamines present in chitin chains. Chitin is the second most abundant polysaccharide on Earth after cellulose, and it is produced in the exoskeleton of crustaceans and insects, and in some parts of the cell walls of fungi. Enzymatic development and the extraction of superior derivatives from chitin wastes – such as chitooligosaccharides with vast importance in the medi­cal and biofuels industry – lead to the necessity of creating chitinases using dif­ferent strains of organisms. In this paper, the chiA gene from the Bacillus lich­eniformis DSM8785 encoding chitinase A (ChiA) with C-terminal hexahis­tid­ine tag was cloned and expressed in the extracellular expression system pYES2 from Saccharomyces cerevisiae INVSc1 as a hyperglycosylated enzyme. The production of recombinant ChiA was successfully confirmed by dot blotting, using anti-His antibodies. The optimal time of expression was identified to be 24 h when galactose was added only at the beginning of fermentation, the chit­in­ase activity starting to decrease after this threshold. Nevertheless, in another experiment, when galactose was added every 24 h for 72 h, the expression con­tinued for the entire period. The purified enzyme was detected, using sodium dodecyl sulphate–polyacrylamide gel electrophoresis (SDS-PAGE), as a het­ero­geneous diffuse band between 80 and 180 kDa. The molecular mass of the same ChiA enzyme expressed in Pichia pastoris KM71H and Escherichia coli BL21 (DE3) was compared using SDS-PAGE with ChiA expressed in S. cere­visiae INVSc1. The activity of ChiA was determined using the fluorogenic substrate, 4-methylumbelliferyl β-d-N,N,N-triacetylchitotrioside (4MUTC). Using a bioinformatics simulation, the number of the glycolsylation sites of the ChiA gene sequence and the proximity of these sites to the alpha factor sequ­ence were hypothesized to be a possible reason for which ChiA enzyme was internally expressed

The effects on human health of non-metallic, semimetals and heavy metals compounds generated by mining activities along the Serbian-Romanian border

This study makes an overview of the chemical pollutants, such as Be and its compounds, S and its compounds, P and its compounds, chlorine and chlorides, Na2O, K2O, Ti2O, CaO, MgO, CuO, SiO2, Al2O3, Fe2O3, Cr2O3, As2O3, that were registered in the mining operations areas in the cross-border region of Romania and Serbia. In addition, their possible effects on human health were discussed. Among the oxides, SiO2, Al2O3, Fe2O3 are the most abundant. From all these pollutants, the most health effects were registered for the compounds of P, S and Ca and the lowest number of health effects was recorded for chlorine. Among the human health effects that have been observed for these compounds, the most common are related to skin, eye and respiratory irritations in the case of acute exposure, but chronic exposure may lead to diseases affecting all the human organs. This information is important for population living in this area, due to air, water and soil pollution, but especially for professional exposure as workers in the mining operations are exposed to higher concentrations of pollutants and for long time

Manganese(III) Porphyrin-based Potentiometric Sensors for Diclofenac Assay in Pharmaceutical Preparations

Two manganese(III) porphyrins: manganese(III) tetraphenylporphyrin chloride and manganese(III)-tetrakis(3-hydroxyphenyl)porphyrin chloride were tested as ionophores for the construction of new diclofenac–selective electrodes. The electroactive material was incorporated either in PVC or a sol–gel matrix. The effect of different plasticizers and additives (anionic and cationic) on the potentiometric response was studied. The best results were obtained for the PVC membrane plasticized with dioctylphtalate and having sodium tetraphenylborate as a lipophilic anionic additive incorporated. The sensor response was linear in the concentration range 3 × 10−6 – 1 × 10−2 M with a slope of −59.7 mV/dec diclofenac, a detection limit of 1.5 × 10−6 M and very good selectivity coefficients. It was used for the determination of diclofenac in pharmaceutical preparations, by direct potentiometry. The results were compared with those obtained by the HPLC reference method and a good agreement was found between the two methods