Fluorine-Containing Drug Administration in Rats Results in Fluorination of Selected Proteins in Liver and Brain Tissue

In many pharmaceuticals, a hydrogen atom or hydroxyl group is replaced by a fluorine to increase bioavailability and biostability. The fate of fluorine released from fluorine-containing drugs is not well investigated. The aim of this study was to examine possible fluorination of proteins in rat liver and brain after administration of the fluorinated drug cinacalcet. We assigned 18 Wistar rats to a control group (n = 6) and a group treated with cinacalcet (2 mg kg⁻¹/body weight, 5 days/week), divided into 7 day (n = 6) and 21 day (n = 6) treatment subgroups. Fluorinated proteins were identified using a free proteomics approach; chromatographic separation and analysis by high-resolution mass spectrometry; peptide/protein identification using the Mascot search algorithm; manual verification of an experimentally generated MS/MS spectrum with the theoretical MS/MS spectrum of identified fluorinated peptides. Three fluorinated proteins (spectrin beta chain; carbamoyl-phosphate synthase [ammonia], mitochondrial; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 1) were identified in the liver and four (spectrin beta chain, dihydropyrimidinase-related protein 4, prominin-2, dihydropyrimidinase-related protein 4) in the brain tissue after 21 days of cinacalcet treatment, but not in the control group. Introduction of fluorine into an organism by administration of fluorinated drugs results in tissue-specific fluorination of proteins.     

New lake district in Europe: origin and hydrochemical characteristics

This article presents a new lake district in Southern Poland created as a result of human activity in the Upper Silesian region. The area has been named the Upper Silesian Anthropogenic Lake District. The lake density of the Lake District as delineated by the authors (with an area of 6766 km²) is 2.74%. It includes 4773 water bodies of various origins – reservoirs retained by dams, flooded mineral workings, water bodies formed in subsidence basins and hollows, levee ponds, residual water bodies following river regulation and other water bodies. These are located in urban‐industrial, rural‐agricultural or quasi‐natural areas. The hydrochemical diversity of water bodies is conditioned by their origin, location in the catchment and function. Studies have shown the widespread occurrence of eutrophication processes in limnic waters within the Lake District. The diverse origin and hydrochemical properties of water bodies within the Upper Silesian Anthropogenic Lake District make it special among other anthropogenic lake districts.     

Acetals and Ethers. XVIII. Reaction products of prop-2-enal and but-2-enal with mixture: n-Aliphatic alcohol and ethylene glycol

The direct condensation reaction of prop-2-enal or but-2-enal with mixture of n-aliphatic alcohol and ethylene glycol, in the presence of p-toluenesulphonic acid as catalyst, leads to a complex mixture of saturated, unsaturated, cyclic and linear acetals, moreover, 2-(2-alkoxy-alkyl)-1,3-dioxolanes are the main reaction products. The detailed investigations for n-butanol showed that unsaturated cyclic acetals: 2-vinyl-1,2-dioxolane 1a or 2-(1-propenyl)-1,3-dioxolane 1b , as well as unsaturated linear acetals: 1,1-dibutoxy-prop-2-en 2a or 1,1-dibutoxy-but-2-en 2b are intermediate reaction products. Additionally, it was found in final products presence of eight by-products: 5-butoxy- 4a or 5-butoxy-7-methyl-1,4-dioxepane 4b , 1,1,3-tributoxypropane 5a or 1,1,3-tributoxybutane 5b , 2-[2-(2-hydroxyethoxy)ethyl]- 6a or 2-[2-(2-hydroxyethoxy)propyl]-1,3-dioxolane 6b , 5-(2-hydroxyethoxy)-7-methyl-1,4-dioxepane 7b , 1,3-dibutoxy-1-(2-hydroxyethoxy)-propane 8a or 1,3-dibutoxy-1-(2-hydroxyethoxy)-butane 8b , 1,1-dibutoxy-3-(2-hydroxyethoxy)-propane 9a or 1,1-dibutoxy-3-(2-hydroxyethoxy)-butane 9b , 3-butoxy-1,1-bis-(2-hydroxyethoxy)-propane 10a or 3-butoxy-1,1-bis-(2-hydroxyethoxy)-butane 10b , and 1-butoxy-1,3-bis-(2-hydroxyethoxy)-propane 11a or 1-butoxy-1,3-bis-(2-hydroxyethoxy)-butane 11b , respectively.     

The Reaction of Malononitrile with Enamines of some cyclic β-Keto acid anilides and amidines

The reaction of enamines 1 derivatives of cyclohexanon- or cycloheptanon-2-carboxylic acid anilides with malononitrile gave in the first step 2-phenylcarbamoyl-cycloalkylideno-malononitriles 3 , which in turn were converted into 1-oxo-2-phenyl-3-amino-4-cyano-cycloalkenoisoquinolines 4 . Enamines containing an adjacent diphenylamidino group 6 reacted with malononitrile giving 1-phenylimino-2-phenyl-3-amino-4-cyano-cycloalkenoisoquinolines 7 . The alkaline hydrolysis of 7 yielded 1-phenylamino-3-oxo-4-cyano-cycloalkenoisoquinoline 8 .     

Effect of Antibiotic Amphotericin B Combinations with Selected 1,3,4-Thiadiazole Derivatives on RPTECs in an In Vitro Model

4-(5-methyl-1,3,4-thiadiazole-2-yl) benzene-1,3-diol (C1) and 4-[5-(naphthalen-1-ylmethyl)-1,3,4-thiadiazol-2-yl] benzene1,3-diol (NTBD) are representative derivatives of the thiadiazole group, with a high antimycotic potential and minimal toxicity against normal human fibroblast cells. The present study has proved its ability to synergize with the antifungal activity of AmB. The aim of this work was to evaluate the cytotoxic effects of C1 or NTBD, alone or in combination with AmB, on human renal proximal tubule epithelial cells (RPTECs) in vitro. Cell viability was assessed with the MTT assay. Flow cytometry and spectrofluorimetric techniques were used to assess the type of cell death and production of reactive oxygen species (ROS), respectively. The ELISA assay was performed to measure the caspase-2, -3, and -9 activity. ATR-FTIR spectroscopy was used to evaluate biomolecular changes in RPTECs induced by the tested formulas. The combinations of C1/NTBD and AmB did not exert a strong inhibitory effect on the viability/growth of kidney cells, as evidenced by the negligible changes in the apoptotic/necrotic rate and caspase activity, compared to the control cells. Both NTBD and C1 displayed stronger anti-oxidant activity when combined with AmB. The relatively low nephrotoxicity of the thiadiazole derivative combinations and the protective activity against AmB-induced oxidative stress may indicate their potential use in the therapy of fungal infections.     

Investigation of the structure of poly(p-chlorophenyl glycidyl ether) by the 13C n.m.r. technique: tacticity and addition isomerism

The p-chlorophenyl glycidyl ether was polymerized in the presence of Al(OiPr)₃, ZnCl₂, SnCl₄, BuOK, KOH and by the Al(OiPr)₃ZnCl₂ 1:1 initiator system. Analysis of the ¹³C n.m.r. spectra of the poly(p-chlorophenyl glycidyl ethers) obtained has made it possible to determine their tacticity and the content of the head-to-tail and head-to-head linkages in the polymer chain.     

Monte Carlo simulation of radiation-induced solid state polymerization

A Monte Carlo method was used for a computer simulation of radiation-induced solid state polymerization. The propagation of polymer chains was simulated by means of self-avoiding random walks on a tetrahedral lattice. The initiation and termination of the chains were modelled by pseudorandom processes. The influence of conditions of the in-source process on the post-polymerization kinetics and on the degree of polymerization of the polymers was studied.     

Determination of the ash yield and the mineral matter content of brown coals by density measurements

A method of measuring the density of bed-moist brown coals based on their plastic properties is described and the feasibility of using the method for determination of the ash yield of the coal is evaluated.     

Integrated instrumental analysis of soft brown coals

A method for the simultaneous determination of calorific value Q^r, ash yieldA^r and total water content W^r_t of soft brown coals is described. The method involves instrumental analysis of brown coal samples using neutron thermalization and gamma back-scattering techniques. Over 80 coal samples (1.1 kg) were analysed, having Q^rvalues up to 15.5 MJ kg^?1,A^r ranging from 3.6 to 76.1 wt% and W^r_t ranging from 11.4 to 61.7 wt%. A comparison of the results from the instrumental method with those of standard laboratory analyses is given, followed by a discussion of the accuracy of the method and of possible ways for improving it.