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AIMS: To analyse the non-glycosylated protein fraction from Melipona beecheii honey for antimicrobial activity against Escherichia coli O157:H7. METHODS AND RESULTS: The proteins from M. beecheii honey were separated according to their degree of glycosylation using Concanavalin A-affinity chromatography. The total protein extract and its fractions were analysed by 1D and 2D electrophoresis. We also determined the antimicrobial and antihaemolytic activities of the total protein extract and the non-glycosylated fraction. Furthermore, we evaluated the effect of this non-glycosylated fraction for the expression of the Stx1, Stx2, EAE and HlyA pathogen genes. Melipona beecheii honey contained at least 24 proteins with molecular weights ranging between 7·6 and 95 kDa and isoelectric points between 3 and 10, three proteins from the 24 are non-glycosylated. The non-glycosylated fraction had an MIC90 of 1·128 µg ml-1 , and this fraction inhibited the haemolytic activity of the pathogen, as well as reduced the expression of Stx1, Stx2 and HlyA. The MbF1-2 protein from the non-glycosylated fraction was sequenced and identified as a homologue of the royal jelly-like protein of Melipona quadrifasciata. CONCLUSIONS: The non-glycosylated protein fraction from M. beecheii honey greatly contributes to antibacterial activity and it is composed of at least three proteins, of which MbF1-2 provided over 50% of the antimicrobial activity. SIGNIFICANCE AND IMPACT OF THE STUDY: The study showed significant antimicrobial activity from several proteins present in the honey of M. beecheii. Interestingly, the non-glycosylated protein fraction demonstrated antihaemolytic activity and adversely affected the expression of virulence genes in Escherichia coli O157:H7; these proteins have the potential to be used in developing therapeutic agents against this bacterium.
Assuntos
Antibacterianos/farmacologia , Abelhas/química , Escherichia coli O157/efeitos dos fármacos , Mel , Proteínas de Insetos/farmacologia , Animais , Antibacterianos/química , Antibacterianos/isolamento & purificação , Escherichia coli O157/genética , Escherichia coli O157/patogenicidade , Expressão Gênica/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Mel/análise , Proteínas de Insetos/química , Proteínas de Insetos/isolamento & purificação , Testes de Sensibilidade Microbiana , Fatores de Virulência/genéticaRESUMO
OBJECTIVE: Despite its use was abandoned several decades ago, the polycationic peptide colistin has become the last hope to treat severe infections caused by multidrug-resistant Gram-negative bacteria. Thus, the development of colistin resistance may seriously compromise the efficacy of treatment. Moreover, colistin has high toxicity being dose dependent. A potentially effective strategy to avoid resistance may be to combine colistin with other antimicrobials. This may help in the rescue of old antimicrobials and in reducing toxic undesired effects. METHODS: Antimicrobial susceptibility determination, efflux machinery function measurements in different conditions and measurement of inhibition of the extrusion by colistin were performed. Moreover, modifications of anisotropy of the membranes by using fluorescent dyes was accomplished. RESULTS: Sub-inhibitory concentrations of colistin have a synergistic effect with several antimicrobials that act intracellularly (targeting protein synthesis and DNA replication). This effect was demonstrated through the uptake increases of acridine orange. in Pseudomonas aeruginosa, Escherichia coli and Acinetobacter baumanii but also in an intrinsically colistin-resistant species as Serratia marcescens. Measurements of the anisotropy of bacterial membranes, as a measure of membrane fluidity, showed significant changes indicative of colistin activity. CONCLUSION: The alterations in the cellular efflux machinery that resulted in higher intracellular concentrations of acridine orange, and likely of other antimicrobials combined with data of membrane fluidity and measured synergism in vitro allow us to envisage the use of these combinations to fight infections caused by multidrug-resistant bacteria.
RESUMO
Bacteria living in biofilms exhibit altered growth phenotypes, while the biofilm provides benefits, the foremost of which is a certain protection against both immune system and killing effect by antimicrobials. Laser-activated irrigation (LAI) and passive ultrasonic irrigation (PUI) have been proposed as alternative methods for cleaning and disinfecting the root canal, as an adjuvant to conventional chemo-mechanical preparation in order to improve debridement and disinfection. Nevertheless, the potential antibacterial effect of LAI using 0.5% of sodium hypochlorite (NaOCl) has received little attention. Glass Pasteur pipettes were used to mimic single-tooth root canal and to build Enterococcus faecalis biofilm. Several irrigants and treatments were assayed for 60 s including (I) Saline, (II) NaOCl 0.5%, (III) NaOCl 5%, (IV) Er,Cr:YSGG, (V) Saline + LAI, (VI) NaOCl 0.5% + LAI, (VII) Saline + PUI, and (VIII) NaOCl 0.5% + PUI. Bacterial reduction was measured by counting the colony-forming units (CFUs). Additionally, AFM visualization and measurement of nano-roughness parameters were used to evaluate LAI effect on bacteria. NaOCl 5% unpowered and NaOCl 0.5% + LAI were capable of eliminating all bacteria, whereas non-activated saline solution and NaOCl 0.5% failed to eliminate E. faecalis. Lower efficiencies were achieved by PUI. Surface analysis by AFM revealed apparent alterations in NaOCl + LAI-treated cells. The Er,Cr:YSGG laser-activated irrigation (LAI) increased the bactericidal efficiency of 0.5% NaOCl against E. faecalis biofilm.
Assuntos
Biofilmes/efeitos dos fármacos , Enterococcus faecalis/fisiologia , Lasers de Estado Sólido , Hipoclorito de Sódio/farmacologia , Antibacterianos/farmacologia , Cavidade Pulpar/microbiologia , Enterococcus faecalis/efeitos dos fármacos , Humanos , Imageamento Tridimensional , Irrigantes do Canal Radicular/farmacologia , UltrassomRESUMO
INTRODUCTION: A great deal of research has addressed problems in the correct acquisition of language, but with few overall conclusions. The reasons for this lie in the individual variability, the existence of different measures for assessing language and the fact that a complex network of genetic and environmental factors are involved in its development. AIM: To review the environmental and genetic variables that have been studied to date, in order to gain a better under-standing of the causes of specific language impairment and create new evidence that can help in the development of screening systems for the early detection of these disorders. DEVELOPMENT: The environmental variables related with poorer early child language development include male gender, low level of education of the mother, familial history of problems with language or psychiatric problems, perinatal problems and health problems in early childhood. Bilingualism seems to be a protective factor. Temperament and language are related. Within the genetic factors there are several specific genes associated with language, two of which have a greater influence on its physiological acquisition: FOXP2 and CNTNAP2. The other genes that are most related with specific language disorders are ATP2C2, CMIP, ROBO2, ZNF277 and NOP9. CONCLUSIONS: The key to comprehending the development of specific language disorders lies in reaching an understanding of the true role played by genes in the ontogenesis, in the regulation of the different developmental processes, and how this role is modulated by the environment.
TITLE: Variables ambientales y geneticas relacionadas con alteraciones en la adquisicion del lenguaje en la infancia.Introduccion. Los problemas en la correcta adquisicion del lenguaje se han estudiado mucho, pero con escasas conclusiones globales; a ello contribuye la variabilidad individual, la existencia de diferentes medidas para evaluar el lenguaje y a que en su desarrollo participa una compleja red de factores geneticos y ambientales. Objetivo. Revisar las variables ambientales y geneticas que se han investigado hasta la actualidad, para comprender mejor las causas de los trastornos especificos del lenguaje y crear nuevas evidencias que faciliten la elaboracion de sistemas de deteccion precoz de estos trastornos. Desarrollo. Dentro de las variables ambientales relacionadas con peor desarrollo en el lenguaje infantil estan el sexo masculino, un nivel educacional maternal bajo, una historia familiar de problemas en el lenguaje o problemas psiquiatricos, los problemas perinatales y los problemas de salud en la infancia. El bilinguismo parece ser un factor protector. El temperamento y el lenguaje tienen relacion. Dentro de los factores geneticos existen ya varios genes especificos asociados con el lenguaje, dos de ellos con una influencia mayor en su adquisicion fisiologica: FOXP2 y CNTNAP2. Los otros genes mas relacionados con trastornos especificos del lenguaje son ATP2C2, CMIP, ROBO2, ZNF277 y NOP9. Conclusiones. La clave para entender el desarrollo de los trastornos especificos del lenguaje radica en llegar a comprender el verdadero papel que desempeñan los genes en la ontogenia, regulando los diferentes procesos de desarrollo y como este papel se ve modulado por el ambiente.
Assuntos
Transtornos do Desenvolvimento da Linguagem/etiologia , Traumatismos do Nascimento/complicações , Criança , Desenvolvimento Infantil , Pré-Escolar , Dislexia/etiologia , Dislexia/genética , Escolaridade , Feminino , Interação Gene-Ambiente , Humanos , Lactente , Recém-Nascido , Doenças do Prematuro , Desenvolvimento da Linguagem , Transtornos do Desenvolvimento da Linguagem/genética , Masculino , Multilinguismo , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/fisiologia , Otite/complicações , Recidiva , Fatores de Risco , Fatores Sexuais , Meio Social , Fatores SocioeconômicosRESUMO
Killer whales (Orcinus orca) in the Mediterranean Sea are currently restricted to the Strait of Gibraltar and surrounding waters. Thirty-nine individuals were present in 2011, with a well-differentiated social structure, organized into five pods. Killer whale occurrence in the Strait is apparently related to the migration of their main prey, Atlantic bluefin tuna (Thunnus thynnus). In spring, whale distribution was restricted to shallow waters off the western coast of the Strait where all pods were observed actively hunting tuna. In summer, the whales were observed in the shallow central waters of the Strait. A relatively new feeding strategy has been observed among two of the five pods. These two pods interact with an artisanal drop-line fishery. Pods depredating the fishery had access to larger tuna in comparison with pods that were actively hunting. The Strait of Gibraltar killer whales are socially and ecologically different from individuals in the Canary Islands. Molecular genetic research has indicated that there is little or no female-mediated gene migration between these areas. Conservation threats include small population size, prey depletion, vessel traffic, and contaminants. We propose the declaration of the Strait of Gibraltar killer whales as an endangered subpopulation. A conservation plan to protect the Strait of Gibraltar killer whales is urgently needed, and we recommend implementation of a seasonal management area where activities producing underwater noise are restricted, and the promotion of bluefin tuna conservation.
Assuntos
Conservação dos Recursos Naturais , Orca/fisiologia , Distribuição Animal , Animais , Ecossistema , Mar Mediterrâneo , Dinâmica PopulacionalRESUMO
Mediterranean Sea long-finned pilot whales (Globicephala melas) are currently classified as Data Deficient on the International Union for the Conservation of Nature (IUCN) Red List. Multiple lines of evidence, including molecular genetic and photo-identification mark-recapture analyses, indicate that the Strait of Gibraltar population (distributed from 5.8°W longitude to west of Djibouti Bank and Alborán Dorsal in the Alborán Sea) is differentiated from the Mediterranean Sea population (east of Djibouti Bank and the Alborán Dorsal up to the Ligurian Sea). There is low genetic diversity within the Mediterranean population, and recent gene flow with the Strait of Gibraltar population is restricted. Current total abundance estimates are lacking for the species in the Mediterranean. Pilot whales in the Alborán Sea region were negatively affected by a morbillivirus epizootic from 2006 to 2007, and recovery may be difficult. The Strait of Gibraltar population, currently estimated to be fewer than 250 individuals, decreased by 26.2% over 5 years after the morbillivirus epizootic. Population viability analyses predicted an 85% probability of extinction for this population over the next 100 years. Increasing maritime traffic, increased contaminant burdens, and occasional fisheries interactions may severely impair the capacity of the Strait of Gibraltar population to recover after the decline due to the pathogen.
Assuntos
Conservação dos Recursos Naturais , Baleias Piloto/fisiologia , Animais , Ecossistema , Mar MediterrâneoRESUMO
Early identification of methicillin-resistant Staphylococcus aureus (MRSA) dominant clones involved in infection and initiation of adequate infection control measures are essential to limit MRSA spread and understand MRSA population dynamics. In this study we evaluated the use of matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF/MS) for the automated discrimination of the major MRSA lineages (clonal complexes, CC) identified in our hospital during a 20-year period (1990-2009). A collection of 82 well-characterized MRSA isolates belonging to the four main CCs (CC5, CC8, CC22 and CC398) was split into a reference set (n = 36) and a validation set (n = 46) to generate pattern recognition models using the ClinProTools software for the identification of MALDI-TOF/MS biomarker peaks. The supervised neural network (SNN) model showed the best performance compared with two other models, with sensitivity and specificity values of 100% and 99.11%, respectively. Eleven peaks (m/z range: 3278-6592) with the highest separation power were identified and used to differentiate all four CCs. Validation of the SNN model using ClinProTools resulted in a positive predictive value (PPV) of 99.6%. The specific contribution of each peak to the model was used to generate subtyping reference signatures for automated subtyping using the BioTyper software, which successfully classified MRSA isolates into their corresponding CCs with a PPV of 98.9%. In conclusion, we find this novel automated MALDI-TOF/MS approach to be a promising, powerful and reliable tool for S. aureus typing.
Assuntos
Técnicas de Tipagem Bacteriana/métodos , Staphylococcus aureus Resistente à Meticilina/classificação , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Algoritmos , Análise por Conglomerados , Diagnóstico Precoce , Humanos , Reconhecimento Automatizado de Padrão , Sensibilidade e Especificidade , Software , Infecções Estafilocócicas/microbiologiaRESUMO
Los biomarcadores de imagen definen características objetivas extraídas de las imágenes médicas, relacionadas con procesos biológicos normales, enfermedades o respuestas terapéuticas. Para desarrollar un biomarcador de imagen es necesario realizar una serie de pasos destinados a validar su relación con la realidad estudiada y controlar su validez, tanto clínica como técnica. Este proceso incluye la definición de pruebas de concepto y de mecanismo; la adquisición estandarizada y optimizada de imágenes anatómicas, funcionales y moleculares; el análisis de los datos mediante modelos computacionales; la visualización adecuada de los resultados; la obtención de medidas estadísticas apropiadas; y la realización de pruebas de principio, eficacia y efectividad. Nuestro objetivo en este trabajo es mostrar los pasos que deben establecerse para aplicar adecuadamente los biomarcadores de imagen, desde su concepción teórica hasta su implantación asistencial, en un entorno hospitalario. Para ello se planteará como ejemplo la valoración de la angiogénesis del cartílago articular (AU)
Imaging biomarkers define objective characteristics extracted from medical images that are related to normal biological processes, diseases, or the response to treatment. To develop an imaging biomarker, it is necessary to carry out a series of steps to validate its relation with the reality studied and to check its clinical and technical validity. This process includes defining tests for the concepts and mechanisms; obtaining standardized and optimized anatomic, functional, and molecular images; analyzing the data with computer models; displaying data appropriately; obtaining the appropriate statistic measures; and conducting tests on the principle, efficacy, and effectiveness. In this article, we aim to explain the steps that must be established to enable biomarkers to be correctly applied, from their theoretical conception to their clinical implementation. To this end, we use the evaluation of angiogenesis in articular cartilage as an example (AU)
Assuntos
Humanos , Masculino , Feminino , Biomarcadores , Bioengenharia/métodos , Bioengenharia/tendências , Imageamento por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética , Inibidores da Angiogênese , Moduladores da Angiogênese , Cartilagem Articular , Sondas Moleculares , Bioengenharia/instrumentação , Bioengenharia/normas , Técnicas de Apoio para a Decisão , Avaliação de Eficácia-Efetividade de Intervenções , 50303RESUMO
Imaging biomarkers define objective characteristics extracted from medical images that are related to normal biological processes, diseases, or the response to treatment. To develop an imaging biomarker, it is necessary to carry out a series of steps to validate its relation with the reality studied and to check its clinical and technical validity. This process includes defining tests for the concepts and mechanisms; obtaining standardized and optimized anatomic, functional, and molecular images; analyzing the data with computer models; displaying data appropriately; obtaining the appropriate statistic measures; and conducting tests on the principle, efficacy, and effectiveness. In this article, we aim to explain the steps that must be established to enable biomarkers to be correctly applied, from their theoretical conception to their clinical implementation. To this end, we use the evaluation of angiogenesis in articular cartilage as an example.
Assuntos
Diagnóstico por Imagem/métodos , Bioengenharia , Estudos de Avaliação como Assunto , Humanos , Estudos de Validação como AssuntoRESUMO
The aim of this study was to describe the prevalence and characteristics of knee prosthetic joint infections due to extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae. From 2000 to 2007, 132 infections out of 5,076 arthroplasties (2.6%) were registered. Seven out of 132 infections (5.3%) were due to ESBL-producing Enterobacteriaceae, Escherichia coli in six cases and Klebsiella pneumoniae in one. Open debridement and retention of the implant was the first surgical approach and all patients received intravenous carbapenems. Relapse was documented in four cases and remission in three. Therefore, debridement without prosthesis removal was associated with a high failure rate.
Assuntos
Antibacterianos/farmacologia , Infecções por Enterobacteriaceae/epidemiologia , Enterobacteriaceae/efeitos dos fármacos , Articulação do Joelho/microbiologia , Infecções Relacionadas à Prótese/epidemiologia , Resistência beta-Lactâmica , Idoso , Carbapenêmicos/uso terapêutico , Desbridamento , Enterobacteriaceae/isolamento & purificação , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/microbiologia , Infecções por Enterobacteriaceae/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Infecções Relacionadas à Prótese/tratamento farmacológico , Infecções Relacionadas à Prótese/microbiologia , Infecções Relacionadas à Prótese/cirurgiaRESUMO
OBJECTIVES: The aim of this study was to characterize the mechanism of resistance to linezolid in an in vitro-selected linezolid-resistant Staphylococcus epidermidis mutant. METHODS: A linezolid-resistant strain of S. epidermidis was selected by serial passages with increasing concentrations of linezolid. The MICs of linezolid, ciprofloxacin, tetracycline, rifampicin, vancomycin, gentamicin, tobramycin, chloramphenicol and oxacillin were determined. The 23S rRNA gene was amplified and sequenced, to search for mutations conferring linezolid resistance. The MIC of linezolid was also determined in the presence of reserpine. Finally, the accumulation of linezolid was measured and quantified by HPLC/UV. RESULTS: The obtained resistant strain had an MIC of linezolid of 64 mg/L and was stable after several passages on blood agar. The MIC measured in the presence of 25 mg/L reserpine, an efflux pump inhibitor, was not altered (MIC of 64 mg/L). The sequence of the 23S rRNA gene showed that the mutation G2576T (Escherichia coli numbering) was not present and no other mutation was found. An analysis of the accumulation of linezolid was performed, comparing the uptake of the resistant strain with that of the susceptible one. This showed that the resistant strain had significantly lower levels of linezolid accumulation than its susceptible parental strain. CONCLUSIONS: The mechanism of resistance to linezolid, in this resistant strain, may be related to a decrease in the antimicrobial uptake. This new mechanism of resistance was also related to a little loss of fitness.
Assuntos
Acetamidas/farmacologia , Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Mutação , Oxazolidinonas/farmacologia , Seleção Genética , Staphylococcus epidermidis/efeitos dos fármacos , Acetamidas/metabolismo , Antibacterianos/metabolismo , Transporte Biológico , Análise Mutacional de DNA , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Humanos , Linezolida , Testes de Sensibilidade Microbiana , Oxazolidinonas/metabolismo , RNA Ribossômico 23S/genética , Análise de Sequência de DNA , Inoculações SeriadasRESUMO
The use of radiopharmaceuticals for the diagnosis of infection is increasing due to their ability to distinguish between septic and aseptic inflammation. The aim of this study was to analyze the intracellular accumulation of technetium-99m-ciprofloxacin in strains of Staphylococcus aureus and Pseudomonas aeruginosa harboring an overexpression of NorA and MexAB-OprM, respectively.
Assuntos
Ciprofloxacina/análogos & derivados , Compostos de Organotecnécio/farmacocinética , Pseudomonas aeruginosa/metabolismo , Compostos Radiofarmacêuticos/farmacocinética , Staphylococcus aureus/metabolismo , Proteínas da Membrana Bacteriana Externa/genética , Proteínas da Membrana Bacteriana Externa/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Ciprofloxacina/farmacocinética , Expressão Gênica , Genes Bacterianos , Humanos , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Infecções por Pseudomonas/diagnóstico por imagem , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/genética , Cintilografia , Infecções Estafilocócicas/diagnóstico por imagem , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/genéticaRESUMO
Anatomic imaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) have been used for many years in clinical oncology. The emergence of positron emission tomography (PET) more than a decade ago was a major breakthrough in the early diagnosis of malignant lesions, as it was based on tumour metabolism and not on anatomy. The merger of both techniques into one thanks to PET-CT cameras has made this technology the most important tool in the management of cancer patients. PET/CT with 18F-FDG is increasingly being used for staging, restaging and treatment monitoring for cancer patients with different types of tumours (lung, breast, colorectal, lymphoma, melanoma, head and neck etc.). At many institutions, PET/CT has replaced separately acquired PET and CT examinations for many oncologic indications. This replacement has occurred despite the fact that only a relatively small number of well designed prospective studies have verified imaging findings against the gold standard of histopathologic tissue evaluation. However, a large number of studies have used acceptable reference standards, such as pathology, imaging and other clinical follow-up findings, for validating PET/CT findings. The impact on the management of patients and the benefits from the information obtained from this anatomo-metabolic procedure justify the term "clinical oncology based on PET-CT" as a new concept to be applied in clinical practice.
Assuntos
Neoplasias/diagnóstico , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Neoplasias da Mama/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Estadiamento de Neoplasias , Neoplasias/diagnóstico por imagem , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias Urogenitais/diagnóstico por imagemRESUMO
Anatomic imaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) have been used for many years in clinical oncology. The emergence of positron emission tomography (PET) more than a decade ago was a major breakthrough in the early diagnosis of malignant lesions, as it was based on tumour metabolism and not on anatomy. The merger of both techniques into one thanks to PET-CT cameras has made this technology the most important tool in the management of cancer patients. PET/CT with 18F-FDG is increasingly being used for staging, restaging and treatment monitoring for cancer patients with different types of tumours (lung, breast, colorectal, lymphoma, melanoma, head and neck etc.). At many institutions, PET/CT has replaced separately acquired PET and CT examinations for many oncologic indications. This replacement has occurred despite the fact that only a relatively small number of well designed prospective studies have verified imaging findings against the gold standard of histopathologic tissue evaluation. However, a large number of studies have used acceptable reference standards, such as pathology, imaging and other clinical follow-up findings, for validating PET/CT findings. The impact on the management of patients and the benefits from the information obtained from this anatomo-metabolic procedure justify the term "clinical oncology based on PET-CT" as a new concept to be applied in clinical practice (AU)
Assuntos
Humanos , Masculino , Feminino , Neoplasias/diagnóstico , Tomografia por Emissão de Pósitrons/métodos , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X/métodos , Tomografia Computadorizada por Raios X , Neoplasias da Mama , Neoplasias Pulmonares , Estadiamento de Neoplasias/métodos , Estadiamento de Neoplasias , Neoplasias , Neoplasias da Glândula Tireoide , Neoplasias UrogenitaisRESUMO
The objective of this study was to analyse an array of ciprofloxacin and norfloxacin derivatives in order to determine those with good activity against bacteria that already present fluoroquinolone resistance associated with mutations in the gyrA and/or parC genes. Four norfloxacin and 20 ciprofloxacin derivatives were synthesised and tested against quinolone-susceptible and -resistant Escherichia coli, Acinetobacter baumannii, Stenotrophomonas maltophilia and Staphylococcus aureus strains using a microdilution test. Among the derivatives, the 4-methyl-7-piperazine ciprofloxacin derivative showed a minimum inhibitory concentration for 50% of the organisms that was 16- and 8-fold lower than ciprofloxacin for A. baumannii and S. maltophilia, respectively. When the methyl group at position 4 in the piperazine ring was substituted by ethyl, butyl or heptyl groups, activity against A. baumannii steadily decreased. The 7-(4-methyl)-piperazine ciprofloxacin derivative (UB-8902) showed very good activity against these multiresistant microorganisms including A. baumannii and S. maltophilia.
Assuntos
Antibacterianos/farmacologia , Ciprofloxacina/análogos & derivados , Ciprofloxacina/farmacologia , Norfloxacino/farmacologia , Resistência Microbiana a Medicamentos , Resistência a Múltiplos Medicamentos , Testes de Sensibilidade Microbiana , Norfloxacino/análogos & derivadosRESUMO
Two quinolone-susceptible Staphylococcus aureus and five quinolone-susceptible Streptococcus pneumoniae isolates were used to obtain in-vitro quinolone-resistant mutants in a multistep resistance selection process. The fluoroquinolones used were ciprofloxacin, moxifloxacin, levofloxacin, gemifloxacin, trovafloxacin and clinafloxacin. The mutagenicity of these quinolones was determined by the Salmonella and the Escherichia coli retromutation assays. All quinolone-resistant Staph. aureus mutants had at least one mutation in the grlA gene, while 86.6% of quinolone-resistant Strep. pneumoniae mutants had mutations in either or both the gyrA and parC genes. Moxifloxacin and levofloxacin selected resistant mutants later than the other quinolones, but this difference was more obvious in Staph. aureus. Accumulation of the fluoroquinolones by Staph. aureus did not explain these differences, since levofloxacin and moxifloxacin accumulated inside bacteria to the same extent as clinafloxacin and trovafloxacin. The results also showed that moxifloxacin and levofloxacin had less mutagenic potency in both mutagenicity assays, suggesting a possible relationship between the selection of resistance to quinolones and the mutagenic potency of the molecule. Furthermore, gemifloxacin selected efflux mutants more frequently than the other quinolones used. Thus, the risk of developing quinolone resistance may depend on the density of the microorganism at the infection site and the concentration of the fluoroquinolone, and also on the mutagenicity of the quinolone used, with moxifloxacin and levofloxacin being the least mutagenic.
Assuntos
Fluoroquinolonas/farmacologia , Fluoroquinolonas/toxicidade , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/genética , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/genética , Compostos Aza/farmacologia , Compostos Aza/toxicidade , Ciprofloxacina/farmacologia , Ciprofloxacina/toxicidade , DNA Girase/genética , DNA Topoisomerase IV/genética , Relação Dose-Resposta a Droga , Farmacorresistência Bacteriana/genética , Gemifloxacina , Levofloxacino , Moxifloxacina , Testes de Mutagenicidade , Naftiridinas/farmacologia , Naftiridinas/toxicidade , Ofloxacino/farmacologia , Ofloxacino/toxicidade , Quinolinas/farmacologia , Quinolinas/toxicidade , Seleção GenéticaRESUMO
CASE REPORT: A 72-year-old man with a large choroidal melanoma was treated with enucleation. Three years later MRI demonstrated images compatible with recurrent tumor in the orbit. PET studies showed no focal hypermetabolic abnormalities. DISCUSSION: In patients after enucleation of choroidal melanoma, conventional imaging techniques can fail to establish differentiation between malignant from post-surgery and benign anatomic abnormalities in orbital tissue that can be detected by PET scanning.
Assuntos
Neoplasias da Coroide/patologia , Melanoma/secundário , Recidiva Local de Neoplasia/diagnóstico , Órbita/patologia , Neoplasias Orbitárias/secundário , Tomografia por Emissão de Pósitrons , Idoso , Neoplasias da Coroide/cirurgia , Diagnóstico Diferencial , Humanos , Imageamento por Ressonância Magnética , Masculino , Melanoma/diagnóstico , Órbita/diagnóstico por imagem , Neoplasias Orbitárias/diagnóstico , RadiografiaRESUMO
Caso clínico: Presentamos el caso de un varón de 72 años con un gran melanoma coroideo que se trató con enucleación. Tres años después presentó en la RNM una posible recidiva orbitaria. El estudio con PET determinó que no había hipermetabolismo en esa zona.Discusión: En pacientes con antecedentes de enucleación por melanoma de coroides, las técnicas de imagen convencionales pueden ser dudosas en diferenciar recidivas tumorales de abnormalidades anatómicas benignas postquirúrgicas de los tejidos orbitarios el diagnóstico de recidiva orbitaria que sí pueden detectar el estudio PET
Case report: A 72-year-old man with a large choroidal melanoma was treated with enucleation. Three years later MRI demonstrated images compatibles with recurrent tumor in the orbit. PET studies showed no focal hypermetabolic abnormalities.Discussion: In patients after enucleation of choroidal melanoma, conventional imaging techniques can fail to establish differentiation between malignant from post-surgery and benign anatomic abnormalities in orbital tissue that can be detected by PET scannig
Assuntos
Masculino , Idoso , Humanos , Melanoma/secundário , Tomografia Computadorizada de Emissão , Neoplasias da Coroide/patologia , Recidiva Local de Neoplasia/diagnóstico , Órbita/patologia , Neoplasias Orbitárias/secundário , Diagnóstico Diferencial , Imageamento por Ressonância Magnética , Melanoma/diagnóstico , Neoplasias da Coroide/cirurgia , Órbita , Neoplasias Orbitárias/diagnósticoRESUMO
This paper describes empirical research on the model, optimization and supervisory control of beer fermentation. Conditions in the laboratory were made as similar as possible to brewery industry conditions. Since mathematical models that consider realistic industrial conditions were not available, a new mathematical model design involving industrial conditions was first developed. Batch fermentations are multiobjective dynamic processes that must be guided along optimal paths to obtain good results. The paper describes a direct way to apply a Pareto set approach with multiobjective evolutionary algorithms (MOEAs). Successful finding of optimal ways to drive these processes were reported. Once obtained, the mathematical fermentation model was used to optimize the fermentation process by using an intelligent control based on certain rules.
Assuntos
Cerveja , Algoritmos , Cerveja/análise , Etanol/metabolismo , Fermentação , Tecnologia de Alimentos , Modelos Biológicos , Saccharomyces cerevisiae/metabolismo , TermodinâmicaRESUMO
OBJECTIVE: To determine whether non-epidemiologically related, antibiotic-resistant isolates of Acinetobacter baumannii from different geographical origins possess common type 1 integrons. METHODS: The epidemiologic relationships between seven A. baumannii strains recovered from different Spanish hospitals were established by pulsed-field gel electrophoresis, the presence of integrons being determined by PCR and DNA sequencing. RESULTS: Integron analysis showed the presence of four different integrons, containing six different known genes (aacC1, aacA4, aadA1, aadB, oxa21 and oxa37) plus an ORF. It was found that the same integron was present in different unrelated strains and that related strains could have different integrons. CONCLUSION: These results show the potential risk of integron dissemination among different strains of A. baumannii.