135 research outputs found

    Intracellular proteome expression during 4-n-nonylphenol biodegradation by the filamentous fungus Metarhizium robertsii

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    4-n-nonylphenol (4-n-NP) is an endocrine disrupting compound (EDC); pollutants that cause serious disturbances in the environment. This study shows the degradation pathway and initial proteome analysis in cultures of a fungus that actively degrades 4-n-NP, Metarhizium robertsii. The research revealed the presence of 14 4-n-NP metabolites formed as a result of the oxidation of the alkyl chain and benzene ring, which leads to the complete decomposition of the compound. Based on the trend and quantitative analysis of the formation of 4-n-NP derivatives, the best conditions for proteome analysis were established. The data collected allowed the formulation of an explanation of the microorganism's strategy towards the removal of 4-n-NP. The main groups of proteins engaged in the removal of the xenobiotic are: oxidation-reduction systems related to nitroreductase-like proteins, ROS defense systems (peroxiredoxin and superoxide dismutase), the TCA cycle and energy-related systems. Principal components analysis was applied to unidentified proteins, resulting in the formulation of three subgroups and initial classification of these proteins

    The role of electron-screening deformations in solar nuclear fusion reactions and the solar neutrino puzzle

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    Thermonuclear fusion reaction rates in the solar plasma are enhanced by the presence of the electron cloud that screens fusing nuclei. The present work studies the influence of electron screening deformations on solar reaction rates in the framework of the Debye-Huckel model. These electron-ion cloud deformations, assumed here to be static and axially symmetric, are shown to be able to considerably influence the solar neutrino fluxes of the pp and the CNO chains, with reasonable changes in the macroscopic parameters of the standard solar model (SSM) . Various known deformation sources are discussed but none of them is found strong enough to have a significant impact on the SSM neutrino fluxes.Comment: Revised version (14 RevTeX pages, 3 ps figures). Accepted for publication in Nuclear Physics

    Triazole-Based Compound as a Candidate To Develop Novel Medicines To Treat Toxoplasmosis

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    This article reports anti-Toxoplasma gondii activity of 3-(thiophen-2-yl)-1,2,4-triazole-5-thione. The compound displayed significant and reproducible antiparasitic effects at nontoxic concentrations for the host cells, with an experimentally determined 50% inhibitory concentration (IC50) at least 30 times better than that of the known chemotherapeutic agent sulfadiazine. Purine nucleoside phosphorylase was defined as the probable target for anti-Toxoplasma activity of the tested compound. These results provide the foundation for future work to develop a new class of medicines to better treat toxoplasmosis

    1,4-disubstituted thiosemicarbazide derivatives are potent inhibitors of toxoplasma gondii proliferation.

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    A series of 4-arylthiosemicarbazides substituted at the N1 position with a 5-membered heteroaryl ring was synthesized and evaluated in vitro for T. gondii inhibition proliferation and host cell cytotoxicity. At non-toxic concentrations for the host cells all studied compounds displayed excellent anti-parasitic effects when compared to sulfadiazine, indicating a high selectivity of their anti-T. gondii activity. The differences in bioactivity investigated by DFT calculations suggest that the inhibitory activity of 4-arylthiosemicarbazides towards T. gondii proliferation is connected with the electronic structure of the molecule. Further, these compounds were tested as potential antibacterial agents. No growth-inhibiting effect on any of the test microorganisms was observed for all the compounds, even at high concentrations

    Hydrophilic interaction chromatography (HILIC) for the determination of cetirizine dihydrochloride

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    AbstractA stability-indicating high-performance liquid chromatography (HPLC) of hydrophilic interactions was developed and validated for the determination of cetirizine dihydrochloride in bulk substance and in pharmaceutical dosage form. The separation was achieved on a Poroshell 120 Hilic (4.6×150mm, 2.7μm) column using a mobile phase composed of acetonitrile–0.1% formic acid (20:80 v/v) at a flow rate of 1.0mL/min. The injection volume was 5.0μL and the wavelength of detection was controlled at 235nm. The method was validated by evaluating linearity, accuracy, precision, selectivity and robustness. Cetirizine dihydrochloride was the susceptible to the action of an oxidation factor. The product of its degradation under those conditions was identified with an EIS-Q-MS mass spectrometer. The hydrophilic interactions between the main analyte, its oxidation product, and the mobile and stationary phases were discussed with the support of a theoretical investigation

    The Influence of Excipients on the Physicochemical and Biological Properties of a Bactericidal, Labile Ester Prodrug in a Salt Form – A Case Study of Cefetamet Pivoxil Hydrochloride

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    The article presents an innovative approach to a bactericidal drug design based on a cephem prodrug analogue – cefetamet pivoxil hydrochloride. The emergence of cefetamet pivoxil hydrochloride excipient systems (mannitol, hydroxypropyl methyl cellulose, pregelatinised starch, lactose monohydrate, magnesium stearate, polyvinylpyrrolidone) caused changes in the physicochemical properties of cefetamet pivoxil hydrochloride. They are significant for planning the development of an innovative pharmaceutical formulation. The biological activity profile of the prodrug was also modified. FTIR spectra were used to study interactions between cefetamet pivoxil hydrochloride and the excipients. The theoretical approach to the analysis of experimental spectra enabled precise indication of cefetamet pivoxil hydrochloride domains responsible for interaction with the excipients. The interactions between cefetamet pivoxil hydrochloride and the excipients resulted in some  important physicochemical modifications: acceptor fluid-dependent changes in solubility and the dissolving rate as well as a decrease in the chemical stability of cefetamet pivoxil hydrochloride in the solid state, especially during thermolysis. The interactions between cefetamet pivoxil hydrochloride and the excipients also had biologically essential effects. There were changes in its permeability through artificial biological membranes simulating the gastrointestinal tract, which depended on the pH value of the acceptor solution. Cefetamet pivoxil hydrochloride combined with the excipient systems exhibited greater bactericidal potential against Staphylococcus aureus. Its bactericidal potential against Enterococcus faecalis, Pseudomonas aeruginosa and Proteus mirabilis doubled. The new approach provides an opportunity to develop treatment of resistant bacterial infections. It will enable synergy between the excipient and the pharmacological potential of an active pharmaceutical substance with modified physicochemical properties induced by the drug carrier

    Non-linear screening corrections of stellar nuclear reaction rates and their effects on solar neutrino fluxes

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    Non-linear electron screening corrections of stellar nuclear fusion rates are calculated analytically in the framework of the Debye-Huckel model and compared with the respective ones of Salpeter's weak screening approximation. In typical solar conditions, the deviation from Salpeter's screening factor is less than one percent, while for hotter stars such corrections turn out to be of the order of one percent only over the limits of the Debye-Huckel model. Moreover, an investigation of the impact of the derived non-linear screening effects on the solar neutrino fluxes yields insignificant corrections for both the pp and CNO chain reactions.Comment: To appear in Phys.Rev.

    Toxoplasma gondii Recombinant antigen AMA1: Diagnostic Utility of Protein Fragments for the Detection of IgG and IgM Antibodies

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    Toxoplasma gondii is an important zoonotic protozoan that infects a wide variety of vertebrates as intermediate hosts. For this reason, the diagnosis of this disease is very important and requires continuous improvement. One possibility is to use recombinant antigens in serological tests. Apical membrane antigen 1 (AMA1), a protein located in specific secretory organelles (micronemes) of T. gondii, is very interesting in regard to its potential diagnostic utility. In the present study, we attempted to identify a fragment of the AMA1 protein with a high sensitivity and specificity for the serological diagnosis of human toxoplasmosis. The full-length AMA1 and two different fragments (AMA1N and AMA1C) were produced using an Escherichia coli expression system. After purification by metal affinity chromatography, recombinant proteins were tested for their utility as antigens in enzyme-linked immunosorbent assays (ELISAs) for the detection of IgG and IgM anti-T. gondii antibodies in human and mouse immune sera. Our data demonstrate that the full-length AMA1 recombinant antigen (corresponding to amino acid residues 67–569 of the native protein) has a better diagnostic potential than its N- or C-terminal fragments. This recombinant protein strongly interacts with specific anti-T. gondii IgG (99.4%) and IgM (80.0%) antibodies, and may be used for developing new tools for diagnostics of toxoplasmosis
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