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1.
Ann Oncol ; 35(1): 66-76, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37866811

RESUMO

BACKGROUND: Checkpoint inhibitor (CPI) therapy revolutionized treatment for advanced non-small-cell lung cancer (NSCLC); however, most patients progress due to primary or acquired resistance. Sitravatinib is a receptor tyrosine kinase inhibitor that can shift the immunosuppressive tumor microenvironment toward an immunostimulatory state. Combining sitravatinib with nivolumab (sitra + nivo) may potentially overcome initial CPI resistance. PATIENTS AND METHODS: In the phase III SAPPHIRE study, patients with advanced non-oncogenic driven, nonsquamous NSCLC who initially benefited from (≥4 months on CPI without progression) and subsequently experienced disease progression on or after CPI combined with or following platinum-based chemotherapy were randomized 1 : 1 to sitra (100 mg once daily administered orally) + nivo (240 mg every 2 weeks or 480 mg every 4 weeks administered intravenously) or docetaxel (75 mg/m2 every 3 weeks administered intravenously). The primary endpoint was overall survival (OS). The secondary endpoints included progression-free survival (PFS), objective response rate (ORR), clinical benefit rate (CBR), duration of response (DOR; all assessed by blinded independent central review), and safety. RESULTS: A total of 577 patients included randomized: sitra + nivo, n = 284; docetaxel, n = 293 (median follow-up, 17.1 months). Sitra + nivo did not significantly improve OS versus docetaxel [median, 12.2 versus 10.6 months; hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.70-1.05; P = 0.144]. The median PFS was 4.4 versus 5.4 months, respectively (HR 1.08, 95% CI 0.89-1.32; P = 0.452). The ORR was 15.6% for sitra + nivo and 17.2% for docetaxel (P = 0.597); CBR was 75.5% and 64.5%, respectively (P = 0.004); median DOR was 7.4 versus 7.1 months, respectively (P = 0.924). Grade ≥3 treatment-related adverse events were observed in 53.0% versus 66.7% of patients receiving sitra + nivo versus docetaxel, respectively. CONCLUSIONS: Although median OS was numerically longer with sitra + nivo, the primary endpoint was not met in patients with previously treated advanced nonsquamous NSCLC. The safety profiles demonstrated were consistent with previous reports.


Assuntos
Anilidas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Piridinas , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Docetaxel/uso terapêutico , Nivolumabe/uso terapêutico , Neoplasias Pulmonares/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Microambiente Tumoral
2.
Rev. colomb. ciencias quim. farm ; 51(1)ene.-abr. 2022.
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1535819

RESUMO

SUMMARY Introduction: Studying the prescription of last generation antibiotics helps to identify the causes and consequences of the inadequate use of antibiotics. These include the appearance of antibacterial resistance, a situation declared by the WHO as a global public health problem. Aim: To describe the prescription of linezolid in a high complexity hospital in Bogotá, Colombia, considering the follow-up of the recommendations for the use of the drug included in clinical practice guidelines (CPG) and its indications. Methods: A descriptive observational study of longitudinal section was performed with retrospective collection of the information of all patients who were prescribed linezolid, at a minimum dose of 600 mg every 12 h during their hospitalization in the period from January 1st, 2017, to December 31st, 2018. The characteristics of linezolid prescription were described. Results: 133 prescriptions were reviewed. The most frequently diagnosed were sepsis of different origin (pulmonary abdominal, urinary) with 22.6 % (30/133), followed by skin and soft tissue infection 16.5 % (22/133), the pneumonia with 12.8 % (17/133) and urinary tract infections with 9.8 % (13/133). Two days treatment was the most frequent (range 1-30 days). In 33 % (44/133) of the patients, linezolid was used empirically (without using a previous antibiotic), while in 40.6 % (54/133) it was used as a second option (a previous antibiotic scheme). It was used as a third option in 20.3 % (27/133). Finally, in 6 % (8/133) of the patients, linezolid was prescribed after three previous antibiotics. It was necessary to use another antibiotic in near fifty percent of patients because linezolid did not work. Conclusions: The present study shows that there is little adherence to the institutional CPGs in relation to the treatment time, the microorganism identification, and the use as first option. The absence of a full-time infectious disease specialist, the high workload and the continuous rotation of prescribing staff may be the cause of these results. Some cases of inappropriate use may be related to the clinical condition of the patient which requires empirical treatments.


Introducción: el estudio de la prescripción de antibióticos de última generación ayuda a identificar las causas y consecuencias del uso inadecuado de antibióticos. Estas incluyen la aparición de resistencia a los antibacterianos, situación declarada por la OMS como un problema de salud pública mundial. Objetivos: describir la prescripción de linezolid en un hospital de alta complejidad de Bogotá, Colombia, teniendo en cuenta el seguimiento de las recomendaciones de uso del fármaco incluidas en las guías de práctica clínica (GPC) y sus indicaciones. Métodos: se realizó un estudio observacional descriptivo de corte longitudinal con recolección retrospectiva de la información de todos los pacientes a los que se les prescribió linezolid, a una dosis mínima de 600 mg cada 12 h durante el período del 1 de enero de 2017 al 31 de diciembre de 2018. Se describieron las características de la prescripción de line-zolid. Resultados: se revisaron 133 prescripciones. Los diagnósticos más frecuentes fueron la sepsis de diferente origen (pulmonar abdominal, urinaria) con el 22,6 % (30/133), seguida de la infección de piel y tejidos blandos con el 16,5 % (22/133), la neumonía con el 12,8 % (17/133) y las infecciones del tracto urinario con un 9,8 % (13/133). El tratamiento de dos días fue el más frecuente (rango 1-30 días). En el 33 % (44/133) de los pacientes se utilizó linezolid de forma empírica (sin utilizar antibiótico previo), mientras que en el 40,6 % (54/133) se utilizó como segunda opción (esquema antibiótico previo). Se utilizó como tercera opción en el 20,3 % (27/133). Finalmente, en el 6 % (8/133) de los pacientes se prescribió linezolid después de tres antibióticos previos. Fue necesario utilizar otro antibiótico en cerca del cincuenta por ciento de los pacientes porque linezolid no funcionó. Conclusiones: existe poca adherencia a las GPC institucionales en lo relacionado con el tiempo de tratamiento, la identificación del microorganismo, y la utilización como primera opción. La falta de un infectólogo de tiempo completo, la alta carga laboral y la continua rotación de personal prescriptor pueden ser las causas de estos resultados. Algunos casos de uso no adecuado pueden estar relacionados con la condición clínica del paciente que obliga a realizar tratamientos empíricos.


Introdução: o estudo da prescrição de antibióticos de última geração auxilia na identificação das causas e consequências do uso inadequado de antibióticos. Entre eles está o surgimento de resistência aos antibacterianos, situação declarada pela OMS como um problema de saúde pública global. Objetivos: descrever a prescrição de linezolida em hospital de alta complexidade de Bogotá, na Colômbia, levando em consideração o acompanhamento das recomendações de uso de medicamentos constantes das diretrizes de prática clínica (CPG) e suas indicações. Métodos: foi realizado um estudo observacional transversal e descritivo com coleta retrospectiva de informações de todos os pacientes que receberam prescrição de linezolida, na dose mínima de 600 mg a cada 12 h durante o período de 1 de janeiro de 2017 a 31 de dezembro de 2018. As características de prescrição da linezolida foram descritas. Resultados: 133 prescrições foram revisadas. Os diagnósticos mais frequentes foram sepse de diferentes origens (pulmonar, abdominal, urinária) com 22,6 % (30/133), seguida de infecção de pele e partes moles com 16,5 % (22/133), pneumonia com 12,8 % (17/133) e infecções do trato urinário com 9,8 % (13/133). O tratamento de dois dias foi o mais frequente (variação de 1-30 dias). Em 33 % (44/133) dos pacientes, a linezolida foi usada empiricamente (sem o uso de antibiótico prévio), enquanto em 40,6 % (54/133) foi usada como segunda opção (esquema antibiótico prévio). Foi utilizada como terceira opção em 20,3 % (27/133). Finalmente, em 6 % (8/133) dos pacientes, linezolida foi prescrito após três antibióticos anteriores. Outro antibiótico teve de ser usado em cerca de 50 por cento dos pacientes porque a linezolida não funcionou. Conclusões: há pouca adesão ao CPG institucional em relação ao tempo de tratamento, a identificação do microrganismo e a utilização como primeira opção. A falta de um infectologista em tempo integral, a alta carga de trabalho e a rotatividade contínua da equipe de prescrição podem ser as causas desses resultados. Alguns casos de uso inadequado podem estar relacionados ao quadro clínico do paciente que necessita de tratamentos empíricos.

3.
Nano Lett ; 21(24): 10157-10164, 2021 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-34846155

RESUMO

In this study, we use differential phase contrast images obtained by scanning transmission electron microscopy combined with computer simulations to map the atomic electrostatic fields of MoS2 monolayers and investigate the effect of sulfur monovacancies and divancancies on the atomic electric field and total charge distribution. A significant redistribution of the electric field in the regions containing defects is observed, with a progressive decrease in the strength of the projected electric field for each sulfur atom removed from its position. The electric field strength at the sulfur monovacancy sites is reduced by approximately 50% and nearly vanishes at the divacancy sites, where it drops to around 15% of the original value, demonstrating the tendency of these defects to attract positively charged ions or particles. In addition, the absence of the sulfur atoms leads to an inversion in the polarity of the total charge distribution in these regions.

4.
Microbiol Resour Announc ; 10(47): e0095221, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34817214

RESUMO

Here, we report the genome sequences of five severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains that were obtained from symptomatic individuals with travel histories during community surveillance in the Dominican Republic in 2020. These sequences provide a starting point for further genomic studies of gene flow and molecular diversity in the Caribbean nation. Phylogenetic analysis suggests that all genomes correspond to the B.1 variant.

5.
Ultramicroscopy ; 225: 113285, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33932733

RESUMO

LiMn2O4 has been considered one of the most promising cathode materials for Li-ion batteries due to its thermal stability, abundance, environmental affinity, and the possibility to exchange Li-ions in three-dimensions. However, it still suffers from major problems, such as capacity fading and voltage decay, which has been associated to phase transformations and dissolution of transition metals. In this report, we use scanning transmission electron microscopy, coupled with differential phase contrast (DPC), to better understand the mechanisms behind the structural transformations occurring in LiMn2O4. We use the fact that DPC has the ability to observe simultaneously light and heavy elements, as well as measure projected electric fields and charge distribution at the atomic level. This approach allows us to monitor the migration of very low amounts of Mn to the Li atomic positions, at the surface and subsurface regions, which otherwise is very challenging to observe using other techniques such as HAADF and ABF. These observations not only provide a fundamental understanding of the structure of LiMn2O4 but also reveal DPC as a novel technique to determine local structural changes in materials consisting of heavy and light elements, as well as identify the location of light elements, monitor low concentrations of substitutional species and identify phase transformations.

6.
Med. intensiva (Madr., Ed. impr.) ; 45(4): 205-210, Mayo 2021. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-222214

RESUMO

Objetivo Evaluar la precisión diagnóstica de los criterios empleados para detectar al paciente realmente portador de microrganismos multirresistentes (MMR). Diseño Estudio prospectivo, observacional de mayo de 2014 a mayo de 2015. Ámbito Unidad de cuidados intensivos polivalente. Pacientes Cohorte de pacientes ingresados de forma consecutiva que cumplían los siguientes criterios de aislamiento preventivo basados en el proyecto «Resistencia Zero»: hospitalización de más de 4 días en los últimos 3 meses («hospital»); antibioterapia durante una semana en el último mes («antibiótico»), pacientes institucionalizados o en contacto con cuidados sanitarios («institución o cuidado»); portador de MMR los últimos 6 meses («MMR previo»). Variables Variables demográficas, resultados de los cultivos obtenidos con presencia o no de MMR y tiempo de aislamiento. Se realizó un análisis multivariable con regresión logística múltiple entre cada uno de los factores de riesgo y el que el paciente fuera portador de MMR. Resultados Durante el periodo de estudio ingresaron 575 pacientes y cumplieron los criterios de aislamiento un 28%. De los 162 pacientes con criterios 51 (31%) eran portadores de MMR y de los que no cumplían criterios 29 (7%) sí que eran portadores. En el análisis multivariable la única variable asociada de forma independiente con el ser portador fue «MMR previo», con una OR 12,14 (IC 95%: 4,24–34,77). Conclusiones El único criterio que se asoció de forma independiente con la capacidad de detectar los pacientes con MMR al ingreso en la UCI fue haber presentado un «MMR previo». (AU)


Objective To assess the diagnostic accuracy of the criteria used to detect patients carrying multiresistant microorganisms (MRMs). Design A prospective observational study was carried out from May 2014 to May 2015. Setting Polyvalent Intensive Care Unit. Patients A cohort of consecutively admitted patients meeting the following criteria for preventive isolation according to the “Zero Resistance” project: hospital length of stay>4 days in the last three months (“hospital”); antibiotherapy during one week in the last month (“antibiotic”); institutionalized patients or recurrent contact with healthcare (“institution or care”); MRM carrier in the last 6 months (“previous MRM”). Variables Demographic data, culture results and isolation time. A multivariate analysis was performed using multiple logistic regression between each of the risk factors and patient MRM carrier status. Results During the study period, 575 patients were admitted, of which 28% met the isolation criteria (162). Fifty-one (31%) were MRM carriers. Of the patients who did not meet the criteria, 29 (7%) were carriers. In the multivariate analysis, the only variable independently associated to carrier status was “previous MRM”, with OR=12.14 (95%CI 4.24-34.77). Conclusions The only criterion independently associated with the ability to detect patients with MRMs upon admission to the ICU was the existence of “previous MRM”. (AU)


Assuntos
Humanos , Unidades de Terapia Intensiva , Isolamento de Pacientes , Estudos Prospectivos
7.
Vet Parasitol Reg Stud Reports ; 23: 100506, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33678363

RESUMO

Forty-eight commercial sheep farms were sampled between the years 2017 and 2019 to evaluate the percentage of reduction of the three families of broad-spectrum anthelmintic drugs available in Costa Rica - benzimidazoles (albendazole), macrocyclic lactones (ivermectin) and imidazothiazoles (levamisole) - in grazing animals by using the fecal egg count reduction test. Animals were selected based on their egg per gram counts after their fecal samples were processed by a modified McMaster technique. The remaining fecal samples were taken to the laboratory for fecal culture and larval identification. The prevalence of farms with albendazole resistance was 100%, ivermectin 96% and levamisole 17%. Seven (n = 47) farms resulted with triple resistance, 39 with double and 1 farm was resistant to 1 AH tested. Haemonchus spp. was the most commonly isolated parasite in pre- and post-treatment larval culture. This is the first report of Oesophagostomum spp. and Teladorsagia sp. resistant to albendazole, Oesophagostomum spp., Teladorsagia sp., Chabertia sp. and Cooperia sp. resistant to ivermectin, and the presence of strains of Haemonchus spp. and Trichostrongylus sp. resistant to the 3 anthelmintics tested. The results of this study demonstrate that anthelmintic resistance is widespread, particularly in Haemonchus spp., and that the major drugs available in the country have lost much of their effectiveness against sheep nematodes.


Assuntos
Anti-Helmínticos , Resistência a Medicamentos , Helmintíase Animal , Doenças dos Ovinos , Animais , Anti-Helmínticos/farmacologia , Anti-Helmínticos/uso terapêutico , Costa Rica/epidemiologia , Fazendas , Helmintíase Animal/tratamento farmacológico , Helmintíase Animal/parasitologia , Contagem de Ovos de Parasitas/veterinária , Ovinos/parasitologia , Doenças dos Ovinos/tratamento farmacológico , Doenças dos Ovinos/epidemiologia , Doenças dos Ovinos/parasitologia
8.
Med Intensiva (Engl Ed) ; 45(4): 205-210, 2021 May.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31780256

RESUMO

OBJECTIVE: To assess the diagnostic accuracy of the criteria used to detect patients carrying multiresistant microorganisms (MRMs). DESIGN: A prospective observational study was carried out from May 2014 to May 2015. SETTING: Polyvalent Intensive Care Unit. PATIENTS: A cohort of consecutively admitted patients meeting the following criteria for preventive isolation according to the "Zero Resistance" project: hospital length of stay>4 days in the last three months ("hospital"); antibiotherapy during one week in the last month ("antibiotic"); institutionalized patients or recurrent contact with healthcare ("institution or care"); MRM carrier in the last 6 months ("previous MRM"). VARIABLES: Demographic data, culture results and isolation time. A multivariate analysis was performed using multiple logistic regression between each of the risk factors and patient MRM carrier status. RESULTS: During the study period, 575 patients were admitted, of which 28% met the isolation criteria (162). Fifty-one (31%) were MRM carriers. Of the patients who did not meet the criteria, 29 (7%) were carriers. In the multivariate analysis, the only variable independently associated to carrier status was "previous MRM", with OR=12.14 (95%CI 4.24-34.77). CONCLUSIONS: The only criterion independently associated with the ability to detect patients with MRMs upon admission to the ICU was the existence of "previous MRM".

9.
Actas dermo-sifiliogr. (Ed. impr.) ; 111(5): 357-363, jun. 2020. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-199351

RESUMO

Los anticoagulantes orales directos (ACOD) emergen como una alternativa más cómoda y segura que los clásicos antagonistas de la vitamina K (AVK); no precisan monitorización, poseen una ventana terapéutica más amplia y tienen menos interacciones farmacológicas. Sin embargo, a pesar de que su uso está cada vez más extendido, existe poco consenso sobre cuál es su manejo perioperatorio óptimo en cirugía dermatológica. En este artículo se describen las características de los ACOD y se revisa la evidencia disponible sobre su uso perioperatorio en la cirugía de la piel


Direct-acting oral anticoagulants (DOACs) have emerged as safer, easier-to-manage alternatives to traditional vitamin K antagonists and are used increasingly because they require no monitoring, have a wider therapeutic window, and react less with other drugs. However, there is little consensus on optimal perioperative management when these drugs are used in dermatologic surgery. This article describes the characteristics of DOACs and reviews current evidence on their use in this setting


Assuntos
Humanos , Anticoagulantes/administração & dosagem , Dermatopatias/cirurgia , Procedimentos Cirúrgicos Dermatológicos/métodos , Perda Sanguínea Cirúrgica/prevenção & controle , Administração Oral
10.
Actas Dermosifiliogr (Engl Ed) ; 111(5): 357-363, 2020 Jun.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32418618

RESUMO

Direct-acting oral anticoagulants (DOACs) have emerged as safer, easier-to-manage alternatives to traditional vitamin K antagonists and are used increasingly because they require no monitoring, have a wider therapeutic window, and react less with other drugs. However, there is little consensus on optimal perioperative management when these drugs are used in dermatologic surgery. This article describes the characteristics of DOACs and reviews current evidence on their use in this setting.


Assuntos
Anticoagulantes , Inibidores do Fator Xa , Administração Oral , Anticoagulantes/efeitos adversos , Procedimentos Cirúrgicos Dermatológicos , Inibidores do Fator Xa/uso terapêutico , Fibrinolíticos/uso terapêutico
11.
ACS Appl Mater Interfaces ; 12(22): 24555-24563, 2020 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-32383580

RESUMO

The purpose of this work is the development of Ag/a:C and Ag-Au/a:C coatings for ureteral stents, to provide them with antimicrobial characteristics. Silver was selected because of its well-known antibacterial properties, while gold was included to assess its capacity to accelerate the silver ion release forming a galvanic couple between Au and Ag. Thus, the metallic (Ag) and bimetallic clusters (Ag-Au) were produced by three different configurations: (i) unbalanced magnetron sputtering (conventional sputtering), (ii) plasma gas condensation process, and by (iii) a combination between both previous approaches. Coatings with Ag-Au bimetallic clusters were characterized by transmission electron microscopy (TEM) in order to study the arrangement (alloy, core-shell, and galvanic couple) of these particles in the carbon matrix. Inductively coupled plasma optical emission spectroscopy (ICP-OES) was used to quantify the Ag ions released through artificial urine from the different coatings deposited on thermoplastic polyurethane tape (one of the materials used in the manufacture of the ureteral stent ). Then, the antibacterial and cytotoxicity properties of Ag and Ag-Au/a:C coatings were evaluated. TEM shows that a biphasic structure was not detected, thus not allowing to anticipate the establishment of a galvanic couple. The ICP-OES results demonstrate that the silver ionization is mainly a function of the amount of silver incorporated in the amorphous carbon (a:C) matrix, and the formation of a bimetallic alloy has a detrimental effect on release of the silver ions. The antibacterial activity was regulated by the silver ionization mechanisms because the coatings with higher Ag release had a higher antibacterial activity.


Assuntos
Antibacterianos/farmacologia , Carbono/química , Materiais Revestidos Biocompatíveis/química , Nanopartículas Metálicas/química , Prata/farmacologia , Stents , Antibacterianos/toxicidade , Materiais Revestidos Biocompatíveis/toxicidade , Escherichia coli/efeitos dos fármacos , Escherichia coli/fisiologia , Fibroblastos/efeitos dos fármacos , Ouro/química , Ouro/toxicidade , Prata/toxicidade
14.
Small ; 14(40): e1802180, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30260591

RESUMO

Mesoporous silica materials have demonstrated a vast spectrum of applications, stimulating an intensive field of study due to their potential use as nanocarriers. Nonetheless, when produced at the nanoscale, their structural characterization is hindered due to the re-arrangement of the pores. To address this issue, this work combines molecular dynamics simulations with electron microscopy computer simulations and experimental results to provide an insight into the structure of amorphous mesoporous silica nanoparticles. The amorphous silica model is prepared using a simple melt-quench molecular dynamics method, while the reconstruction of the mesoporous nanoparticles is carried out using a methodology to avoid false symmetry in the final model. Simulated scanning transmission electron microscopy images are compared with experimental images, revealing the existence of structural domains, created by the misalignment of the pores to compensate the surface tension of these spherical nanoparticles.

15.
Brain Struct Funct ; 223(3): 1229-1253, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29101523

RESUMO

Synaptic inputs from cortex and thalamus were compared in electrophysiologically defined striatal cell classes: direct and indirect pathways' striatal projection neurons (dSPNs and iSPNs), fast-spiking interneurons (FS), cholinergic interneurons (ChINs), and low-threshold spiking-like (LTS-like) interneurons. Our purpose was to observe whether stimulus from cortex or thalamus had equivalent synaptic strength to evoke prolonged suprathreshold synaptic responses in these neuron classes. Subthreshold responses showed that inputs from either source functionally mix up in their dendrites at similar electrotonic distances from their somata. Passive and active properties of striatal neuron classes were consistent with the previous studies. Cre-dependent adeno-associated viruses containing Td-Tomato or eYFP fluorescent proteins were used to identify target cells. Transfections with ChR2-eYFP driven by the promoters CamKII or EF1.DIO in intralaminar thalamic nuclei using Vglut-2-Cre mice, or CAMKII in the motor cortex were used to stimulate cortical or thalamic afferents optogenetically. Both field stimuli in the cortex or photostimulation of ChR2-YFP cortical fibers evoked similar prolonged suprathreshold responses in SPNs. Photostimulation of ChR2-YFP thalamic afferents also evoked suprathreshold responses. Differences previously described between responses of dSPNs and iSPNs were observed in both cases. Prolonged suprathreshold responses could also be evoked from both sources onto all other neuron classes studied. However, to evoke thalamostriatal suprathreshold responses, afferents from more than one thalamic nucleus had to be stimulated. In conclusion, both thalamus and cortex are capable to generate suprathreshold responses converging on diverse striatal cell classes. Postsynaptic properties appear to shape these responses.


Assuntos
Córtex Cerebral/fisiologia , Corpo Estriado/citologia , Vias Neurais/fisiologia , Neurônios/fisiologia , Potenciais Sinápticos/fisiologia , Tálamo/fisiologia , Análise de Variância , Animais , Colina O-Acetiltransferase/metabolismo , Estimulação Elétrica , Antagonistas de Aminoácidos Excitatórios/farmacologia , Feminino , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Lisina/análogos & derivados , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Vias Neurais/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Potenciais Sinápticos/efeitos dos fármacos , Proteína Vesicular 2 de Transporte de Glutamato/genética , Proteína Vesicular 2 de Transporte de Glutamato/metabolismo
16.
Nanoscale ; 9(16): 5254-5262, 2017 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-28397926

RESUMO

In this work, oxidation of carbon supported Zn nanostructures was studied to elucidate their utilization as oxygen scavenging materials activated by the relative humidity in the environment. Moisture-activated nano-scavengers were produced on carbon substrates using magnetron sputtering attaining nano-islands (nanoparticles), randomly distributed on the carbon surface, with arbitrary crystallographic orientations. They possess a Zn-ZnO core-shell structure, caused by surface passivation, which provides them with a self-assembled protective layer that prevents complete oxidation of nanoparticles prior to utilization. The oxidation rate is independent of the nanoparticle size and orientation, for particles between 5 and 18 nm. The oxidation kinetics are not in complete agreement with the Cabrera and Mott theory. When exposed to a high relative humidity environment, an acceleration in the oxidation process is observed, dissolving the Zn nanoparticles and forming a layer on the carbon, which facilitates the consumption of the Zn to form ZnO. These results support the idea of its potential use in applications where high RH environments are required, such as food packaging.

17.
Tuberculosis (Edinb) ; 101S: S35-S44, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27733245

RESUMO

Pathogens frequently exploit or evade inflammasome activation in order to survive and proliferate. Alternatively, inadequate inflammasome activation by attenuated microorganisms or adjuvanted subunit vaccines may contribute to poor longevity of protection. To further understand these pathways, we determined the differential inflammasome transcriptome of human THP monocyte-derived macrophages in response to Mycobacterium bovis BCG, as compared to LPS or Trypanosoma cruzi. The results identify the highly specific innate recognition programs associated with inflammasome activation by human macrophages exposed to these microbial stimuli. BCG, T. cruzi, and LPS strongly induced expression of both unique and overlapping genes downstream of TLR signaling pathways including cytokines and chemokines that mediate inflammation and regulate cell death pathways. Compared to LPS, BCG failed to directly activate anti-apoptotic molecules and multiple NLR and inflammasome complex components including caspase-1, and actively repressed important signaling intermediates in AP-1 and NFκB transcription factor pathways. Both BCG and T. cruzi repressed expression of TXNIP, an anti-oxidant inhibitor that recruits caspase-1 to the NLRP3 inflammasome, while T. cruzi infection uniquely failed to activate TNF-α. These results identify unique pathogen specific strategies to activate inflammation and modulate cell death that may drive inflammatory outcomes and suggest avenues of investigation to optimize host immunity.


Assuntos
Vacina BCG/farmacologia , Inflamassomos/metabolismo , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/parasitologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Trypanosoma cruzi/patogenicidade , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Linhagem Celular , Citocinas/metabolismo , Interações Hospedeiro-Patógeno , Humanos , Imunidade Inata/efeitos dos fármacos , Inflamassomos/efeitos dos fármacos , Inflamassomos/genética , Inflamassomos/imunologia , Lipopolissacarídeos/farmacologia , Macrófagos/imunologia , Macrófagos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo , Receptores Toll-Like/metabolismo , Trypanosoma cruzi/imunologia
18.
Mater Sci Eng C Mater Biol Appl ; 55: 547-55, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26117788

RESUMO

Nowadays, with the increase of elderly population and related health problems, knee and hip joint prosthesis are being widely used worldwide. However, failure of these invasive devices occurs in a high percentage thus demanding the revision of the chirurgical procedure. Within the reasons of failure, microbial infections, either hospital or subsequently-acquired, contribute in high number to the statistics. Staphylococcus epidermidis (S. epidermidis) has emerged as one of the major nosocomial pathogens associated with these infections. Silver has a historic performance in medicine due to its potent antimicrobial activity, with a broad-spectrum on the activity of different types of microorganisms. Consequently, the main goal of this work was to produce Ag-ZrCN coatings with antimicrobial activity, for the surface modification of hip prostheses. Thin films of ZrCN with several silver concentrations were deposited onto stainless steel 316 L, by DC reactive magnetron sputtering, using two targets, Zr and Zr with silver pellets (Zr+Ag target), in an atmosphere containing Ar, C2H2 and N2. The antimicrobial activity of the modified surfaces was tested against S. epidermidis and the influence of an activation step of silver was assessed by testing samples after immersion in a 5% (w/v) NaClO solution for 5 min. The activation procedure revealed to be essential for the antimicrobial activity, as observed by the presence of an inhibition halo on the surface with 11 at.% of Ag. The morphology analysis of the surface before and after the activation procedure revealed differences in silver distribution indicating segregation/diffusion of the metallic element to the film's surface. Thus, the results indicate that the silver activation step is responsible for an antimicrobial effect of the coatings, due to silver oxidation and silver ion release.


Assuntos
Anti-Infecciosos/farmacologia , Materiais Revestidos Biocompatíveis , Cianetos/química , Prata/química , Zircônio/química , Anti-Infecciosos/química , Microscopia Eletrônica de Varredura , Espectroscopia Fotoeletrônica
19.
An. pediatr. (2003, Ed. impr.) ; 82(1): e78-e81, ene. 2015. tab
Artigo em Espanhol | IBECS | ID: ibc-131675

RESUMO

La enfermedad inflamatoria intestinal (EII) es un trastorno inflamatorio crónico del tracto intestinal de patogénesis multifactorial, con posible asociación a distintos desórdenes autoinmunes, entre los cuales se encuentra la hepatitis autoinmune (HAI). Se ha postulado una serie de características diferenciales de la EII asociada a HAI en niños. Nuestro objetivo es describir las características diferenciales observadas en nuestros pacientes con EII asociada a HAI respecto a aquellos con formas clásicas de la enfermedad, confirmando dicha singularidad


Inflammatory bowel Disease (IBD) is a group of chronic inflammatory diseases that can be associated with different autoimmune diseases, including autoimmune hepatitis (AIH).Some specific and differential characteristics in children with IBD associated to AIH have beendescribed. Our aim is to describe the clinical pattern of this association observed in our patients,confirming its differential characteristics as compared to classical IBD in children


Assuntos
Humanos , Feminino , Criança , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/metabolismo , Colite Ulcerativa/patologia , Colangite/diagnóstico , Trato Gastrointestinal/anormalidades , Colite Ulcerativa/complicações , Colite Ulcerativa/prevenção & controle , Colangite/metabolismo , Trato Gastrointestinal/lesões
20.
J Mech Behav Biomed Mater ; 41: 83-91, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25460405

RESUMO

This study aims to evaluate the structural, mechanical and tribological properties of zirconium carbonitrides (ZrCxN1-x) coatings with embedded silver nanoparticles, produced with the intention of achieving a material with enhanced multi-functional properties, including mechanical strength, corrosion resistance, tribological performance and antibacterial behavior suitable for their use in joint prostheses. The coatings were deposited by direct current (DC) reactive magnetron sputtering onto 316 L stainless steel, changing the silver content from 0 to 20 at% by modifying the current density applied to the targets. Different nitrogen and acetylene gas fluxes were used as reactive gases. The coatings revealed different mixtures of crystalline ZrCxN1-x, silver nanoparticles and amorphous carbon phases. The hardness of the films was found to be mainly controlled by the ratio between the hard (ZrCxN1-x) and soft (Ag and amorphous carbon) phases in the films, fluctuating between 7.4 and 20.4 GPa. The coefficient of friction, measured against ultra-high molecular weight polyethylene (UHMWPE) in Hank's balanced salt solution with 10 gL(-1) albumin, is governed by the surface roughness and hardness. The UHMWPE wear rates were in the same order of magnitude (between 1.4 and 2.0 × 10(-6)mm(3)N(-1)m(-1)), justified by the effect of the protective layer of albumin formed during the tests. The small differences were due to the hydrophobic/hydrophilic character of the surface, as well as to the silver content.


Assuntos
Materiais Revestidos Biocompatíveis/química , Prótese Articular , Fenômenos Mecânicos , Nanopartículas Metálicas/química , Polietilenos/química , Prata/química , Zircônio/química , Fricção , Dureza , Propriedades de Superfície
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