An efficient microwave-assisted synthesis and biological properties of polysubstituted pyrimidinyl- and 1,3,5-triazinylphosphonic acids

Polysubstituted pyrimidinylphosphonic and 1,3,5-triazinylphosphonic acids with potential biological properties were prepared in high yields by the microwave-assisted Michaelis Arbuzov reaction of trialkyl phosphite with the corresponding halopyrimidines and halo-1,3,5-triazines, respectively, followed by the standard deprotection of the phosphonate group using TMSBr in acetonitrile. 4,6-Diamino-5chloropyrimidin-2-ylphosphonic acid (7a) was found to exhibit a weak to moderate anti-influenza activity (28-50 uM) and may represent a novel hit for further SAR studies and antiviral improvement. (C) 2011 Elsevier Ltd. All rights reserved.status: publishe

Microbiological quality of powdered infant formula in Latin America

Cronobacter is a bacterial genus that includes seven species, and the species Cronobacter sakazakii is most related to meningitis and septicemia in infants associated with powdered infant formula (PIF). The objectives of this study were to evaluate the presence of C. sakazakii and to determine the microbiological quality of PIF for infant consumption. To do this, a total of 128 PIF samples were analyzed in four brands and countries (Chile, Mexico, Holland, and Brazil), considering three types of PIF: premature (PIF1), infant (PIF2), and follow-up (PIF3). Aerobic plate counts (APC) and Enterobacteriaceae (ENT) were assessed in accordance with Chilean official standards. The outer membrane protein A (ompA) gene was amplified to detect Cronobacter spp. and the fusA gene was amplified to identify C. sakazakii by using the PubMLST Web site and BLAST (NCBI). The antibiotic resistance profile was performed according to the Clinical and Laboratory Standards Institute standards. The pathogen was quantified by the most probable number (MPN). The results showed that APC median values for PIF1, PIF2, and PIF3 were 3.2, 4.9, and 4.8 log CFU g(-1), respectively. The APC were higher in PIF2 (P < 0.01) from Holland (P < 0.01) in the commercial brand 4 (P < 0.01). The ENT median values in PIF1, PIF2, and PIF3 were 1.8, 1.5, and 1.7 log CFU g(-1), respectively. Five strains of C. sakazakii and one strain of Cronobacter malonaticus were identified as having values between 0.023 and 2.3 MPN/g. All strains (100%) harbored the ompA, plasminogen activator (cpa), and hemolysin (hly) virulence genes. To conclude, C. sakazakii was found in four PIF samples from four Chilean products and one from Mexico, which is distributed throughout America. C. sakazakii strains exhibit virulence factors and resistance to ampicillin, thus posing a risk when PIFs are consumed by infants.Research Directorate of the Universidad del Bio-Bio 191520 4 Research Directorate of the Universidad del Bio-Bio (Regular and Grupo de Investigación) 171220 Research Directorate of the Universidad del Bio-Bio (En Formación) Research Directorate of the Universidad del Bio-Bio (Comisión Nacional de Investigación Cientifica y Tecnológica/Fondo de Financiamiento de Investigación en Áreas Prioritarias [CONICYT/FONDAP]) 1513001

The effect of novel [3-fluoro-(2-phosphonoethoxy)propyl]purines on the inhibition of Plasmodium falciparum, Plasmodium vivax and human hypoxanthine-guanine-(xanthine) phosphoribosyltransferases

Protozoan parasites from the Plasmodiidae family are the causative agents of malaria. Inhibition of hypoxanthine-guanine-(xanthine) phosphoribosyltransferase (HG(X)PRT) has been suggested as a target for development of new anti-malarial therapeutics. Acyclic nucleoside phosphonates (ANPs) are potent and selective inhibitors of plasmodial HG(X)PRTs. A new series of ANPs, based on the chemical structure and inhibitory activity of three ANPs, 2-(phosphonoethoxy)ethyl with either guanine or hypoxanthine as the base (PEEG and PEEHx) and 3-hydroxy-2-(phosphonomethoxy)propyl with guanine as the base (HPMPG), were prepared. These compounds are stereoisomers of 3-fluoro-(2-phosphonoethoxy)propyl (FPEPs) and 3-fluoro-(2-phosphonomethoxy) propyl (FPMPs) analogues. Both the (R)- and (S)-isomers of these fluorinated derivatives have higher K values (by 10- to 1000-fold) for human HGPRT and Plasmodium falciparum HGXPRT than the non-fluorinated ANPs. Possible explanations for these changes in affinity are proposed based on docking studies using the known crystal structures of human HGPRT in complex with PEEG

Seroprevalence of Measles Antibodies in the Population of the Olomouc Region, Czech Republic&mdash;Comparison of the Results of Four Laboratories

Objectives: Although the incidence of measles has decreased globally since the introduction of regular vaccination, its frequency has increased again in recent years. The study is focused on data from the Olomouc Region in the Czech Republic analyzed in four laboratories. The obtained results were compared with already published data. Methods: The data were provided by individual laboratories in an anonymized form&mdash;age at the time of the examination, sex, and result of test. Samples were collected between June 2018 and September 2019 and evaluated on the scale positive&ndash;borderline&ndash;negative. Results: A total of 7962 sera samples were evaluated using three different methods&mdash;two types of ELISA tests and CLIA. Positive result was issued in a total of 62.6 percent of samples, but the results of individual laboratories varied widely from 55.5 to 70.8 percent. However, the same trend with the highest levels of antibodies in people born before beginning of vaccination was observed. Conclusions: Data show significantly different results depending on the individual laboratories and the detection kits used. The underestimation of the proportion of positive results can cause problems in selecting individuals for revaccination with a live vaccine, which may fail in weakly positive individuals

Implantace energetických Au iontů do ZnO nanopilířů pro modulaci optické odezvy

Nanopillars of ZnO were implanted with Au-400 keV ions at various ion fluences from 1 x 10(15) cm(-2) to 1 x 10(16) cm(-2) and subsequently annealed at 750 degrees C for 15 min in order to reduce the implantation damage and to support Au nanoparticle (NP) aggregation. It was found that implantation-induced effects and thermal effects influence the Au NP coalescence as well as the quality of the ZnO nanopillars. Rutherford Back-Scattering spectrometry (RBS) showed the broader Au-depth profiles than it was theoretically predicted, but the Au-concentration maximum agrees well with prediction taking into account the effective ZnO layer density. The implantation at the higher fluences induced the morphology modification of the nanopillar layer evidenced by RBS and scanning electron microscopy (SEM). An indirect evidence of this effect was given by optical ellipsometry due to gradual refractive index changes in the ZnO nanopillars with the increased Au-ion fluence. Optical characterization of the Au-implanted and annealed nanopillars performed by means of photoluminescence (PL) and diffuse-reflectance spectroscopy (DRS) evidenced the surface plasmon resonance (SPR) activity of the embedded Au NPs. The SPR-enhanced scattering and PL emission observed in the spectral range 500-650 nm are ascribed to Au NPs or more complex Au-clusters. In addition, the ellipsometry measurements of extinction coefficient are found to corroborate well results from DRS, both indicating increase of SPR effect with the increase of Au-ion fluence and after the post-annealing.Do nanopilířů ZnO byly implantovány ionty Au-400 keV při různých fluktuacích iontů od 1 x 10(15) cm(-2) do 1 x 10(16) cm(-2) a následně žíhány při 750 stupních C po dobu 15 min, aby se snížilo poškození implantace a podpořila se agregace nanočástic Au (NP). Bylo zjištěno, že efekty vyvolané implantací a tepelné efekty ovlivňují koalescenci Au NP a také kvalitu nanopilířů ZnO. Rutherfordova zpětná rozptylová spektrometrie (RBS) ukázala širší profily hloubky Au, než bylo teoreticky předpovězeno, ale maximum koncentrace Au dobře souhlasí s predikcí, která bere v úvahu efektivní hustotu vrstvy ZnO. Implantace při vyšších fluencesách vyvolala morfologickou modifikaci nanopilární vrstvy doloženou RBS a rastrovací elektronovou mikroskopií (SEM). Nepřímý důkaz tohoto efektu poskytla optická elipsometrie v důsledku postupných změn indexu lomu v nanopilárech ZnO se zvýšeným fluencem Au-iontů. Optická charakterizace Au-implantovaných a žíhaných nanopilárů provedená pomocí fotoluminiscence (PL) a difuzně-reflexní spektroskopie (DRS) prokázala aktivitu povrchové plasmonové rezonance (SPR) vložených Au NP. SPR-enhanced rozptyl a PL emise pozorované ve spektrálním rozsahu 500-650 nm jsou připisovány Au NP nebo složitějším Au-klastrům. Kromě toho bylo zjištěno, že elipsometrická měření extinkčního koeficientu dobře potvrzují výsledky z DRS, což ukazuje na zvýšení účinku SPR se zvýšením fluence Au-iontů a po následném žíhání

DataSheet_1_Complex molecular profile of DNA repair genes in epithelial ovarian carcinoma patients with different sensitivity to platinum-based therapy.pdf

Epithelial ovarian carcinoma (EOC) is known for high mortality due to diagnosis at advanced stages and frequent therapy resistance. Previous findings suggested that the DNA repair system is involved in the therapeutic response of cancer patients and DNA repair genes are promising targets for novel therapies. This study aimed to address complex inter-relations among gene expression levels, methylation profiles, and somatic mutations in DNA repair genes and EOC prognosis and therapy resistance status. We found significant associations of DUT expression with the presence of peritoneal metastases in EOC patients. The high-grade serous EOC subtype was enriched with TP53 mutations compared to other subtypes. Furthermore, somatic mutations in XPC and PRKDC were significantly associated with worse overall survival of EOC patients, and higher FAAP20 expression in platinum-resistant than platinum-sensitive patients was observed. We found higher methylation of RAD50 in platinum-resistant than in platinum-sensitive patients. Somatic mutations in BRCA1 and RAD9A were significantly associated with higher RBBP8 methylation in platinum-sensitive compared to platinum-resistant EOC patients. In conclusion, we discovered associations of several candidate genes from the DNA repair pathway with the prognosis and platinum resistance status of EOC patients, which deserve further validation as potential predictive biomarkers.</p