RESUMEN

ZnO materials with spherical morphology, core-shell and solid, disperse or interconnected, were obtained by a completely green synthesis via a carbohydrate-template route. Morphology, structure and optical properties, as well as antimicrobial potential and cytocompatibility were investigated. The antimicrobial efficiency of the obtained materials was screened against a large spectrum of reference and clinical microbial strains, both susceptible and exhibiting resistance phenotypes of clinical and epidemiological interest, in planktonic and biofilm state. Their biocidal activity is strongly dependent of material's characteristics and target microorganism. One of the most valuable findings of our study is the good antibiofilm activity of the obtained nanostructures, which in some cases was superior to that noted against planktonic cells, despite the well-known high tolerance of biofilm-embedded cells to different stressor agents. Another important finding is the excellent efficiency against three Gram-negative, respectively Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae and two Gram-positive species, i.e. Staphylococcus aureus and Enteroccus faecium included in the ESKAPE list of the most dangerous resistant pathogens, requiring global surveillance and urgent need for the development of novel antimicrobial agents. Our study offers the first insight regarding the high therapeutic potential of ZnO nanoparticles against the fearful nosocomial pathogen A. baumannii. The cytocompatibility of the developed materials in terms of cell morphology, viability and proliferation, revealed a comparable dose-dependent cellular response, at the active antimicrobial concentrations, only a low effect on cell viability is evidenced. Overall, our data demonstrated the potential of the materials for antimicrobial applications and also that their biotoxicity can be modulated directly through their morpho-structural characteristics.

Asunto(s)

Antiinfecciosos/síntesis química , Nanopartículas del Metal/química , Óxido de Zinc/química , Antiinfecciosos/química , Antiinfecciosos/farmacología , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Nanopartículas del Metal/toxicidad , Pruebas de Sensibilidad Microbiana , Microscopía Fluorescente , Espectroscopía Infrarroja por Transformada de Fourier , Difracción de Rayos X

RESUMEN

Two ZnO materials of spherical hierarchical morphologies, with hollow (ZnOHS) and solid cores (ZnOSS), were obtained through the hydrolysis of zinc acetylacetonate in 1,4-butanediol. The nature of the defects and surface reactivity for the two ZnO materials were investigated through photoluminescence, X-ray photoelectron spectroscopy, and electron paramagnetic resonance (EPR) spectroscopy proving the coexistence of shallow and deep defects and, also, the presence of polyol byproducts adsorbed on the outer layers of the ZnO samples. The EPR spectroscopy coupled with the spin-trapping technique showed that the surface of the ZnO samples generates reactive oxygen species (ROS) like hydroxyl (•OH) and singlet oxygen (1O2) as well as carbon-centered radicals. The ZnO materials exhibited a wide spectrum of antimicrobial activity, being active against Gram-positive, Gram-negative, and fungi strains, both in planktonic and, more importantly, adherent growth states. The decrease of antimicrobial efficiency in the presence of a ROS scavenger (mannitol) and the decrease of the cell viability with the ROS level suggest that one of the mechanisms that governs both the antimicrobial and cytotoxic activities on human liver cells is ROS-mediated. However, at active antimicrobial concentrations, the biocompatibility of the tested materials is very good.

Asunto(s)

Antibacterianos/farmacología , Nanoestructuras/química , Óxido de Zinc/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Antibacterianos/toxicidad , Candida albicans/efectos de los fármacos , Cryptococcus neoformans/efectos de los fármacos , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Células Hep G2 , Humanos , Hidroxibutiratos/química , Radical Hidroxilo/síntesis química , Pruebas de Sensibilidad Microbiana , Nanoestructuras/toxicidad , Pentanonas/química , Oxígeno Singlete/química , Óxido de Zinc/síntesis química , Óxido de Zinc/química , Óxido de Zinc/toxicidad

RESUMEN

Deferiprone is used as a chelation agent in chronic iron overload in ß-thalassemia patients. Patients on deferiprone therapy show variable response to this drug in terms of reduction in iron overload as well as adverse drug reactions (ADRs). The pharmacogenetic studies on deferiprone have not carried out in patients with blood disorders in India. Therefore, the present study was carried out to evaluate the three most common nonsynonymous UGT1A6 polymorphisms Thr181Ala (541 A/G), Arg184Ser (552 A/C) and Ser7Ala (19 T/G) and therapeutic response to deferiprone in ß-thalassemia major patients. Two hundred and eighty six (286) ß-thalassemia major patients were involved in the study. Serum ferritin levels were estimated periodically to assess the status of the iron overload and the patients were grouped into responders and non-responders depending on the ferritin levels. The UGT1A6 2 polymorphisms were detected by PCR-RFLP methods. The association between the genotypes and outcome as well as ADRs was evaluated by Open EPI software. A significant difference was observed in the genotypic distribution of UGT1A6 2 Thr181Ala polymorphism in responders and non-responders. However, there was no difference in the genotypic distribution between patients with and without ADRs. As far as the UGT1A6 2 Arg184Ser polymorphism is concerned, no significant difference was observed between responders and non-responders. Further, evaluating the association of UGT1A6 2 Ser7Ala polymorphism with drug response, there was no significant difference in the genotypic distribution between responders and non-responders. However, there was a significant difference between responders with and without ADRs and non-responders with and without ADRs. In addition to this haplotype analysis was also carried out. However, we did not find any specific haplotype to be significantly associated with the deferiprone response in ß-thalassemia major patients.

Asunto(s)

Glucuronosiltransferasa/genética , Quelantes del Hierro/uso terapéutico , Mutación Missense , Polimorfismo de Nucleótido Simple , Piridonas/uso terapéutico , Talasemia beta/tratamiento farmacológico , Talasemia beta/genética , Adolescente , Alanina/genética , Sustitución de Aminoácidos/genética , Arginina/genética , Niño , Preescolar , Deferiprona , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Humanos , Quelantes del Hierro/efectos adversos , Sobrecarga de Hierro/epidemiología , Sobrecarga de Hierro/genética , Sobrecarga de Hierro/prevención & control , Isoenzimas/genética , Masculino , Mutación Missense/fisiología , Polimorfismo de Nucleótido Simple/fisiología , Piridonas/efectos adversos , Serina/genética , Treonina/genética , Resultado del Tratamiento , Talasemia beta/epidemiología