Tyrosol induces multiple drug resistance in yeast Saccharomyces cerevisiae

In yeast, multiple (pleiotropic) drug resistance (MDR) transporters efflux xenobiotics from the cytoplasm to the environment. Additionally, upon the accumulation of xenobiotics in the cells, MDR genes are induced. At the same time, fungal cells can produce secondary metabolites with physico-chemical properties similar to MDR transporter substrates. Nitrogen limitation in yeast Saccharomyces cerevisiae leads to the accumulation of phenylethanol, tryptophol, and tyrosol, which are products of aromatic amino acid catabolism. In this study, we investigated whether these compounds could induce or inhibit MDR in yeast. Double deletion of PDR1 and PDR3 genes, which are transcription factors that upregulate the expression of PDR genes, reduced yeast resistance to high concentrations of tyrosol (4–6 g/L) but not to the other two tested aromatic alcohols. PDR5 gene, but not other tested MDR transporter genes (SNQ2, YOR1, PDR10, PDR15) contributed to yeast resistance to tyrosol. Tyrosol inhibited the efflux of rhodamine 6G (R6G), a substrate for MDR transporters. However, preincubating yeast cells with tyrosol induced MDR, as evidenced by increased Pdr5-GFP levels and reduced yeast ability to accumulate Nile red, another fluorescent MDR-transporter substrate. Moreover, tyrosol inhibited the cytostatic effect of clotrimazole, the azole antifungal. Our results demonstrate that a natural secondary metabolite can modulate yeast MDR. We speculate that intermediates of aromatic amino acid metabolites coordinate cell metabolism and defense mechanisms against xenobiotics

Antibacterial and photochemical properties of cellulose nanofiber-titania nanocomposites loaded with two different types of antibiotic medicines

Nanocomposite dermal drug delivery systems based on cellulose nanofibers with grafted titania nanoparticles loaded by two antibiotic medicines from different classes, i.e. tetracycline (TC) and phosphomycin (Phos), were successfully produced by a ‘‘green chemistry’’ approach in aqueous media. The influence of a different surface binding mechanism between the drug molecule and modified cellulose nanofibers on the release of the drug and, as a result, on antimicrobial properties against common pathogens Gram-positive, Staphylococcus aureus and Gram-negative Escherichia coli was investigated. The disk diffusion method and broth culture tests using varying concentrations of drugs loaded to nanocomposites were carried out to investigate the antibacterial effects. The influence of UV irradiation on the stability of the obtained nanocomposites and their antibacterial properties after irradiation were also investigated, showing enhanced stability especially for the TC loaded materials. These findings suggest that the obtained nanocomposites are promising materials for the development of potentially useful antimicrobial patches

Crystal structure of new carboxylate phosphabetaines and phosphonium salts conjugated with them

© 2016, Springer Science+Business Media New York.Earlier unknown crystalline forms of three carboxylate phosphabetaines and conjugated with them phosphonium salts differing by β substituent with respect to the carboxylate group were studied. The structure of studied compounds in crystal is determined by intermolecular electrostatic interactions. This leads to the trans arrangement of the carboxylate and the phosphonium groups

HISTORY AND MODERN MODEL Of NEPHROLOGY SERVICE IN MULTIPROfILE HOSPITAL

The purpose of the study was to present the stages of effective nephrological service forming and to evaluate the output results of the Regional Nephrological Center (RNC) as the unit of multidisciplinary hospital. Results and discussion. The nephrology service of State Novosibirsk Regional Clinical Hospital began to form in 1978 with the opening of nephrology hemodialysis and kidney transplantation departments. The RNC was established in 1993 on the base of a territorial register for patients with chronic renal failure. Currently, the RNC includes the department of nephrology, the register for patients with chronic kidney disease (CKD) of 3–5 stages, nephrological counseling office, offices for potential recipients of renal transplantation and for patients with transplanted kidney, the office of permanent outpatient peritoneal dialysis. As a result, the prevalence and structure of CKD 3–5 stages in the Novosibirsk region are comparable to those in Europe, the availability of the renal replacement therapy, including the number of patients with a functioning renal transplant exceeds the nationwide indicators. Conclusion. The model of the nephrological service of a multidisciplinary hospital provides accounting and dispensation of patients with CKD, increases the effectiveness of treatment, including methods of renal replacement therapy

Triphenylphosphine in reactions with ω-haloalkylcarboxylic acids

© 2016 Taylor & Francis Group, LLC.Stable phosphonium salts were synthesized by the phosphorylation of a series of ω-haloalkylcarboxylic acids with triphenylphosphine. In a second step the resulting phosphonium salts have been treated with 1 M aqueous solution of sodium hydroxide to form the corresponding carboxylate phosphabetaines. The structure of the isolated compounds was determined by IR and NMR spectroscopy, elemental analysis, and X-ray crystallographic studies. Their thermal stability was studied by simultaneous thermogravimetry and differential scanning calorimetry

Synthesis and biological evaluation of novel carboxylate phosphabetaines derivatives with long alkyl chains

© 2016 Taylor & Francis Group, LLC.The purpose of the present study was to investigate the antibacterial activity of novel alkyl esters of carboxylate phosphabetaine: β-(carboxyalkyl)ethyltributylphosphonium bromides 4–8. The in vitro microbiological activity of the synthesized phosphonium bromides against gram-positive, gram-negative bacteria and the yeast Candida albicans was determined in comparison to standard agents. Microbiological results indicate the synthesized phosphonium salts possess a broad spectrum of activity against the testedmicroorganisms. Every newly synthesized compound was characterized by elemental analyses, IR, 1H NMR, 31P NMR spectral studies

Serum uromodulin as an early biomarker of tubular atrophy and interstitial fibrosis in patients with glomerulopathies

Aim. To assess the significance of the serum uromodulin (Tamm-Horsfall protein - THP) concentration (Sumo) as an early biomarker of tubular atrophy (TA) and interstitial renal fibrosis (IF) in patients with glomerulopathies. Materials and methods. 84 patients with glomerulopathy and 11 practically healthy persons (control) were examined. Uromodulin concentrations in serum and urine (Uumo) were measured, renal excretion of this protein and the estimated glomerular filtration rate (eGFR) were established. A semi-quantitative assessment of nephrobioptates was performed. Results and discussion. Sumo decreases with a minimum expression of tubular atrophy (TA) or interstitial fibrosis (IF), when the values of eGFR still remain normal. Variations of such excretory parameters of THP as Uumo, daily excretion, and ratio: urinary uromodulin / urinary creatinine, did not manifest a similar trend. Conclusion. Sumo is promising as an early biomarker of fibrotic and atrophic renal damage. The parameters of renal excretion of THP do not seem to have this property. The reason for the delay in the decline of Uumo in the progression of CKD as compared to the decrease in Sumo seems to be the need to maintain a sufficient Uumo to counteract urinary tract infection and stone formation

Synthesis, structure, and antimicrobial activity of (carboxyalkyl)dimethylsulfonium halides

© 2017, Pleiades Publishing, Ltd. Reactions of a series of ω-halocarboxylic acids (2-bromo-, 2-chloroethanoic, 3-bromo- and 3-chloropropanoic) with dimethyl sulfide resulted in the formation of stable (carboxylalkyl)dimethylsulfonium bromides and chlorides. Composition and structure of the salts obtained were established by a complex of chemical, physical and physicochemical methods. The sulfonium salts obtained showed high antibacterial and antimycotic activities with respect to the pathogenic microflora of humans and animals

INNOVATIVE TECHNOLOGIES IN DIAGNOSIS AND TREATMENT OF EXTREME FAMILIAL HYPERCHOLESTEROLEMIA

The article reveals medical and social relevance of extreme familial hypercholesterolemia. It presents the main principles, innovative technologies and an algorithm of diagnosis, diagnostic verification, risk stratification of patients and optimization of the use of aggressive combined cholesterol-lowering drug treatment and precision of indications for plasma exchange and the lack of options