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Eur Heart J ; 41(5): 645-651, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31237939


AIMS: To determine the 1-year risk of stroke and other adverse outcomes in patients with a new diagnosis of perioperative atrial fibrillation (POAF) after non-cardiac surgery. METHODS AND RESULTS: The PeriOperative ISchemic Evaluation (POISE)-1 trial evaluated the effects of metoprolol vs. placebo in 8351 patients, and POISE-2 compared the effect of aspirin vs. placebo, and clonidine vs. placebo in 10 010 patients. These trials included patients with, or at risk of, cardiovascular disease who were undergoing non-cardiac surgery. For the purpose of this study, we combined the POISE datasets, excluding 244 patients who were in atrial fibrillation (AF) at the time of randomization. Perioperative atrial fibrillation was defined as new AF that occurred within 30 days after surgery. Our primary outcome was the incidence of stroke at 1 year of follow-up; secondary outcomes were mortality and myocardial infarction (MI). We compared outcomes among patients with and without POAF using multivariable adjusted Cox proportional hazards models. Among 18 117 patients (mean age 69 years, 57.4% male), 404 had POAF (2.2%). The stroke incidence 1 year after surgery was 5.58 vs. 1.54 per 100 patient-years in patients with and without POAF, adjusted hazard ratio (aHR) 3.43, 95% confidence interval (CI) 2.00-5.90; P < 0.001. Patients with POAF also had an increased risk of death (incidence 31.37 vs. 9.34; aHR 2.51, 95% CI 2.01-3.14; P < 0.001) and MI (incidence 26.20 vs. 8.23; aHR 5.10, 95% CI 3.91-6.64; P < 0.001). CONCLUSION: Patients with POAF have a significantly increased risk of stroke, MI, and death at 1 year. Intervention studies are needed to evaluate risk reduction strategies in this high-risk population.

Cell Rep ; 29(8): 2270-2283.e7, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31747600


Interleukin (IL)-17 signaling to the intestinal epithelium regulates the intestinal microbiome. Given the reported links between intestinal dysbiosis, bacterial translocation, and liver disease, we hypothesize that intestinal IL-17R signaling plays a critical role in mitigating hepatic inflammation. To test this, we study intestinal epithelium-specific IL-17RA-deficient mice in an immune-driven hepatitis model. At the naive state, these mice exhibit microbiome dysbiosis and increased translocation of bacterial products (CpG DNA), which drives liver IL-18 production. Upon disease induction, absence of enteric IL-17RA signaling exacerbates hepatitis and hepatocyte cell death. IL-18 is necessary for disease exacerbation and is associated with increased activated hepatic lymphocytes based on Ifng and Fasl expression. Thus, intestinal IL-17R regulates translocation of TLR9 ligands and constrains susceptibility to hepatitis. These data connect enteric Th17 signaling and the microbiome in hepatitis, with broader implications on the effects of impaired intestinal immunity and subsequent release of microbial products observed in other extra-intestinal pathologies.

Trials ; 20(1): 622, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31694684


BACKGROUND: Use of minimally invasive surgical techniques for lung resection surgery (LRS), such as video-assisted thoracoscopy (VATS), has increased in recent years. However, there is little information about the best anesthetic technique in this context. This surgical approach is associated with a lower intensity of postoperative pain, and its use has been proposed in programs for enhanced recovery after surgery (ERAS). This study compares the severity of postoperative complications in patients undergoing LRS who have received lidocaine intraoperatively either intravenously or via paravertebral administration versus saline. METHODS/DESIGN: We will conduct a single-center randomized controlled trial involving 153 patients undergoing LRS through a thoracoscopic approach. The patients will be randomly assigned to one of the following study groups: intravenous lidocaine with more paravertebral thoracic (PVT) saline, PVT lidocaine with more intravenous saline, or intravenous remifentanil with more PVT saline. The primary outcome will be the comparison of the postoperative course through Clavien-Dindo classification. Furthermore, we will compare the perioperative pulmonary and systemic inflammatory response by monitoring biomarkers in the bronchoalveolar lavage fluid and blood, as well as postoperative analgesic consumption between the three groups of patients. We will use an ANOVA to compare quantitative variables and a chi-squared test to compare qualitative variables. DISCUSSION: The development of less invasive surgical techniques means that anesthesiologists must adapt their perioperative management protocols and look for anesthetic techniques that provide good analgesic quality and allow rapid rehabilitation of the patient, as proposed in the ERAS protocols. The administration of a continuous infusion of intravenous lidocaine has proven to be useful and safe for the management of other types of surgery, as demonstrated in colorectal cancer. We want to know whether the continuous administration of lidocaine by a paravertebral route can be substituted with the intravenous administration of this local anesthetic in a safe and effective way while avoiding the risks inherent in the use of regional anesthetic techniques. In this way, this technique could be used in a safe and effective way in ERAS programs for pulmonary resection. TRIAL REGISTRATION: EudraCT, 2016-004271-52;, NCT03905837 . Protocol number IGGFGG-2016 version 4.0, 27th April 2017.

Artigo em Inglês | MEDLINE | ID: mdl-31603987


The NLRP3 inflammasome has emerged as an important regulator of metabolic disorders and age-associated diseases as reported in NLRP3 deficient mice. Here we asked whether in old mice C57BL6J the NLRP3 inflammasome inhibitor MCC950 is able to attenuate age- assocociated metabolic syndrome providing health benefits. We report that MCC950 attenuates metabolic and hepatic dysfunction in aged mice. MCC950 inhibited the Pi3K/AKT/mTOR pathway, and enhanced autophagy and activated peroxisome proliferator-activated receptor alpha (PPARα) in vivo and in vitro. The data suggest that MCC950 mediates the protective effects by mTOR inhibiton activating autophagy and PPARα. In conclusion, pharmacological inhibition of NLRP3 in aged mice has a significant impact on health. Thus, NLRP3 may be a therapeutic target of human age-associated metabolic syndrome.

rev. cuid. (Bucaramanga. 2010) ; 10(1): e621, ene.-abr. 2019. tab
Artigo em Espanhol | LILACS-Express | ID: biblio-1043566


Resumen Introducción La obesidad predispone a que los ancianos puedan sufrir una caída. El objetivo de este estudio fue contrastar las diferencias entre los factores de riesgo de caídas y el Índice de Masa Corporal en el adulto mayor hospitalizado. Materiales y Métodos Estudio descriptivo y comparativo realizado en un Hospital de Especialidades de Veracruz, México. El muestreo fue no probabilístico por conveniencia con una muestra constituida por 122 adultos mayores hospitalizados en las áreas de urgencias, ginecología y medicina interna. Los factores de riesgo de caídas se midieron con la escala de caída de Morse. Además de datos sociodemográficos, antropométricos y de salud. Se usó estadística descriptiva e inferencial como Kruskal-Wallis, Chi Cuadrada y V de Cramer. Resultados La media de edad fue 70.94±7.50 años e Índice de Masa Corporal de 28.66±3.80; antecedente de caídas, tener catéteres intravenosos y la falta de actividad física fueron factores de riesgo predominantes. Se encontró una diferencia estadística significativa entre la marcha y el Índice de Masa Corporal (p<0.05 y V de Cramer=0.204). Discusión El Índice de Masa Corporal es un dato importante porque se asocia con problemas en la marcha. Conclusiones La marcha es un factor de riesgo de caída que tiene diferencias significativas con el Índice de Masa Corporal, debido a que los ancianos con sobrepeso tuvieron una marcha alterada, que puede impedir mantener el equilibrio y como consecuencia una posible caída.

Abstract Introduction Obesity makes the elderly prone to the risk of falling. The aim of this study was to contrast the differences between the risk factors for falls and the Body Mass Index in elderly hospitalized patients. Materials and Methods A descriptive-comparative study was conducted at a Medical Specialties Hospital in Veracruz, Mexico. Convenience sampling was not probabilistic with a sample composed of 122 elderly hospitalized patients in the hospital emergency, gynecology and internal medicine departments. Risk factors for falls were measured using the Morse Fall Scale, in addition to the sociodemographic, anthropometric and health data. Descriptive inferential statistics such as Kruskal-Wallis test, Chi-squared test and Cramér's V were used. Results Age average was 70.94±7.50 and Body Mass Index was 28.66±3.80; Predominant risk factors were a history of previous falls, having intravenous catheters and lack of physical activity. A statistically significant difference was found between gait and the Body Mass Index (p<0.05 and Cramér's V=0.204). Discussion Body Mass Index is a very important factor because it can be associated with gait problems. Conclusions Gait is a risk factor for falls that has significant differences with the Body Mass Index. This is because elderly who are overweight had an abnormal gait that could make difficult to maintain balance so that a possible fall could happen.

Resumo Introdução A obesidade é um fator de predisposição às quedas nos idosos. Este estudo objetiva contrastar as diferenças entre os fatores de risco de quedas e o Índice de Massa Corporal no adulto maior hospitalizado. Materiais e Métodos Estudo descritivo e comparativo realizado em um Hospital de Especialidades de Veracruz, México. A amostragem foi não probabilística por conveniência com uma amostra constituída por 122 adultos maiores hospitalizados nas áreas de urgências, ginecologia e medicina interna. Os fatores de risco de quedas foram mensurados com a escala de quedas de Morse, em conjunto com outros dados sociodemográficos, antropométricos e de saúde. Foram utilizadas estatísticas descritivas e inferenciais como Kruskal-Wallis, Chi Cuadrada e V de Cramer. Resultados A média de idade foi de 70.94±7.50 anos e um Índice de Massa Corporal de 28.66±3.80; antecedente de quedas, ter cateteres intravenosos e a falta de atividade física foram fatores de risco predominantes. Verificou-se uma diferença significativa entre a caminhada e o Índice de Massa Corporal (p<0.05 e V de Cramer=0.204). Discussão O Índice de Massa Corporal é um dado importante porque ele está associado a problemas na caminhada. Conclusões A caminhada é um fator de risco de queda que tem diferenças significativas com o Índice de Massa Corporal, sendo que os idosos com sobrepeso apresentaram uma caminhada alterada, que lhes impede manter o equilíbrio e em decorrência disso produzir possíveis quedas.

Anticancer Res ; 38(9): 5393-5400, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30194194


BACKGROUND/AIM: Predicting response to treatment in high-grade serous ovarian carcinoma (HGSOC) still remains a clinical challenge. The standard-of-care for first-line chemotherapy, based on a combination of carboplatin and paclitaxel, achieves a high response rate. However, the development of drug resistance is one of the major limitations to efficacy. Therefore, identification of biomarkers able to predict response to chemotherapy in patients with HGSOC is a critical step for prognosis and treatment of the disease. Several studies suggest that angiogenesis is an important process in the development of ovarian carcinoma and chemoresistance. The aim of this study was to identify a profile of angiogenesis-related genes as a biomarker for response to first-line chemotherapy in HGSOC. MATERIALS AND METHODS: Formalin-fixed paraffin-embedded samples from 39 patients with HGSOC who underwent surgical cytoreduction and received a first-line chemotherapy with carboplatin and paclitaxel were included in this study. Expression levels of 82 angiogenesis-related genes were measured by quantitative real-time polymerase chain reaction using TaqMan low-density arrays. RESULTS: Univariate analysis identified five genes [angiopoietin 1 (ANGPT1), aryl hydrocarbon receptor nuclear translocator (ARNT), CD34, epidermal growth factor (EGF) and matrix metallopeptidase 3 (MMP3)] as being statistically associated with response to treatment. Multivariable analysis by Lasso-penalized Cox regression generated a model with the combined expression of seven genes [angiotensinogen (AGT), CD34, EGF, erythropoietin receptor (EPOR), interleukin 8 (IL8), MMP3 and MMP7)]. The area under the receiver operating characteristics curve (0.679) and cross-validated Kaplan-Meier survival curves were used to estimate the accuracy of these predictors. CONCLUSION: An angiogenesis-related gene expression profile useful for response prediction in HGSOC was identified, supporting the important role of angiogenesis in HGSOC.

Proteínas Angiogênicas/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Perfilação da Expressão Gênica/métodos , Neoplasias Císticas, Mucinosas e Serosas/tratamento farmacológico , Neoplasias Císticas, Mucinosas e Serosas/genética , Neovascularização Patológica/genética , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Medicina de Precisão/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Carboplatina/administração & dosagem , Tomada de Decisão Clínica , Procedimentos Cirúrgicos de Citorredução , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Análise Multivariada , Gradação de Tumores , Neoplasias Císticas, Mucinosas e Serosas/patologia , Neoplasias Ovarianas/patologia , Paclitaxel/administração & dosagem , Seleção de Pacientes , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Curva ROC , Fatores de Risco , Transcriptoma
ACS Omega ; 3(4): 3760-3767, 2018 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-30023878


Two new brominated bis(indole) alkaloids, dragmacidins I (1) and J (2), showing low micromolar cytostatic activity, along with three known congeners were isolated from the Tanzanian sponge Dragmacidon sp. and their structures determined by the analysis of their NMR and MS data. From the study of their mechanism of action, it can be concluded that the mitotic arrest at metaphase in treated tumor cells, mediated by inhibition of PP1 and/or PP2A phosphatases is involved in the observed antiproliferative activity. Differences in their bioactivities were rationalized, and a plausible binding mode is proposed on the basis of computational simulations.

Rev. bras. anestesiol ; 68(2): 200-204, Mar.-Apr. 2018. tab, graf
Artigo em Inglês | LILACS-Express | ID: biblio-897815


Abstract In recent years, laser resection of lung metastases has been established as the standard procedure worldwide. To avoid airway fire, it is necessary to collapse the surgical lung. The selective lobar bronchial blockade is a technique that allows one-lung ventilation while the operated lobe is collapsed in patients with previous pulmonary resection requiring subsequent resection or with limited pulmonary reserve. We report a clinical case about our experience of a selective lobar bronchial blockade technique with a bronchial blocker (Coopdech endobronchial blocker) that was employed successfully with a double-lumen endotracheal tube in a patient with previous contralateral pulmonary resection who was scheduled for atypical resections of pulmonary metastases by laser. We selectively blocked the right intermediate bronchus for management of hypoxemia during one-lung ventilation. This technique provided adequate ventilation and oxygenation during surgery, avoiding the need of two-lung ventilation during lung metastases resection by laser. Conclusion: This case shows that if a properly positioned double-lumen tube was already in place and the patient does not tolerate one-lung ventilation because of hypoxemia, it would be possible to provide selective lobar blockade by placing a bronchial blocker through the lumen of the double-lumen tube, avoiding the use of continuous positive airway pressure during laser surgery. This technique does not disturb the operative field or interrupt the operative procedure during resection by laser, which would occur during two-lung ventilation or used of continuous positive airway pressure.

Resumo Nos últimos anos, a ressecção de metástases pulmonares com o uso de laser foi estabelecida como o procedimento padrão em todo o mundo. Para evitar queimadura das vias aéreas, o colapso cirúrgico do pulmão é necessário. O bloqueio brônquico seletivo é uma técnica que permite a ventilação de um lobo, enquanto o lobo operado é colapsado nos pacientes com ressecção pulmonar anterior que requerem ressecção subsequente ou que possuem reserva pulmonar limitada. Relatamos um caso clínico de nossa experiência com a técnica de bloqueio brônquico seletivo com bloqueador brônquico (bloqueador endobrônquico Coopdech), usado com sucesso com um tubo endotraqueal de duplo lúmen em um paciente com ressecção pulmonar contralateral prévia, agendado para ressecção atípica de metástases pulmonares com o uso de laser. Seletivamente bloqueamos o brônquio intermediário direito para o controle de hipoxemia durante a ventilação monopulmonar. Essa técnica proporcionou ventilação e oxigenação adequadas durante a cirurgia, evitando a necessidade de ventilar os dois pulmões durante a ressecção de metástases pulmonares com o uso de laser. Conclusão: Este caso mostra que, se um tubo de duplo lume estiver corretamente posicionado e o paciente não tolerar a ventilação monopulmonar devido à hipoxemia, seria possível fornecer bloqueio lobar seletivo com a colocação de um bloqueador brônquico através do lume do tubo de duplo lume, evitando o uso de pressão positiva contínua de vias aéreas (PPCVA) durante a cirurgia a laser. Essa técnica não interfere no campo operatório ou interrompe o procedimento durante a ressecção por laser, que poderia ocorrer durante a ventilação dos dois pulmões ou uso de PPCVA.

Toxicology ; 398-399: 41-51, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29486218


Metabolic factors are the major risk of non-alcoholic fatty liver disease, although other factors may contribute steatosis. Cadmium exposure produces histopathological and molecular changes in liver, which are consistent with steatosis. In the present study, we describe the effect of low cadmium acute treatment on hepatocytes obtained from mice fed with a high cholesterol diet. Our data suggest that hepatocytes with cholesterol overload promote an adaptive response against cadmium-induced acute toxicity by up-regulating anti-apoptotic proteins, managing ROS overproduction, increasing GSH synthesis and MT-II content to avoid protein oxidation. Cadmium treatment increases lipid content in cholesterol-fed mice hepatocytes because of an impaired autophagy process. Our data suggest an essential function of macroautophagy in the regulation of lipid storage induced by Cd on hepatocytes, that implies that alterations in this pathway may be a mechanism that aggravates hepatic steatosis.

Cloreto de Cádmio/toxicidade , Fígado Gorduroso/etiologia , Hepatócitos/efeitos dos fármacos , Hiperlipidemias/etiologia , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Colesterol/administração & dosagem , Dieta/efeitos adversos , Fígado Gorduroso/induzido quimicamente , Fígado Gorduroso/patologia , Hepatócitos/patologia , Hiperlipidemias/induzido quimicamente , Hiperlipidemias/patologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Distribuição Aleatória
J Med Screen ; 25(3): 119-125, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-28992757


OBJECTIVE: To use the results of the first five years of a cystic fibrosis newborn screening program to estimate the cystic fibrosis birth prevalence and spectrum of cystic fibrosis transmembrane conductance regulator ( CFTR) gene variants in Yucatan, Mexico. METHODS: Screening was performed from 2010 to 2015, using two-tier immunoreactive trypsinogen testing, followed by a sweat test. When sweat test values were >30 mmol/L, the CFTR gene was analyzed. RESULTS: Of 96,071 newborns screened, a second sample was requested in 119 cases. A sweat test was performed in 30 newborns, and 9 possible cases were detected (seven confirmed cystic fibrosis and two inconclusive). The most frequently detected CFTR pathogenic variant (5/14 cystic fibrosis alleles, 35.7%) was p.(Phe508del); novel p.(Ala559Pro) and p.(Thr1299Hisfs*29) pathogenic variants were found. CONCLUSIONS: Cystic fibrosis birth prevalence in southeastern Mexico is 1:13,724 newborns. Immunoreactive trypsinogen blood concentration is influenced by gestational age and by the time of sampling. The spectrum of CFTR gene variants in Yucatan is heterogeneous.

Regulador de Condutância Transmembrana em Fibrose Cística/genética , Fibrose Cística/sangue , Fibrose Cística/diagnóstico , Mutação , Triagem Neonatal/métodos , Alelos , Fibrose Cística/genética , Feminino , Humanos , Recém-Nascido , Masculino , México/epidemiologia , Prevalência , Reprodutibilidade dos Testes , Suor , Tripsinogênio/sangue
Rev Bras Anestesiol ; 68(2): 200-204, 2018.
Artigo em Português | MEDLINE | ID: mdl-28526465


In recent years, laser resection of lung metastases has been established as the standard procedure worldwide. To avoid airway fire, it is necessary to collapse the surgical lung. The selective lobar bronchial blockade is a technique that allows one-lung ventilation while the operated lobe is collapsed in patients with previous pulmonary resection requiring subsequent resection or with limited pulmonary reserve. We report a clinical case about our experience of a selective lobar bronchial blockade technique with a bronchial blocker (Coopdech endobronchial blocker) that was employed successfully with a double-lumen endotracheal tube in a patient with previous contralateral pulmonary resection who was scheduled for atypical resections of pulmonary metastases by laser. We selectively blocked the right intermediate bronchus for management of hypoxemia during one-lung ventilation. This technique provided adequate ventilation and oxygenation during surgery, avoiding the need of two-lung ventilation during lung metastases resection by laser. CONCLUSION: This case shows that if a properly positioned double-lumen tube was already in place and the patient does not tolerate one-lung ventilation because of hypoxemia, it would be possible to provide selective lobar blockade by placing a bronchial blocker through the lumen of the double-lumen tube, avoiding the use of continuous positive airway pressure during laser surgery. This technique does not disturb the operative field or interrupt the operative procedure during resection by laser, which would occur during two-lung ventilation or used of continuous positive airway pressure.

Intubação Intratraqueal/instrumentação , Terapia a Laser , Neoplasias Pulmonares/cirurgia , Ventilação Monopulmonar/instrumentação , Adulto , Desenho de Equipamento , Humanos , Neoplasias Pulmonares/secundário , Masculino , Procedimentos Cirúrgicos Pulmonares/instrumentação , Procedimentos Cirúrgicos Pulmonares/métodos
Ann Surg ; 268(2): 357-363, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-28486392


OBJECTIVE: To determine the prognostic relevance, clinical characteristics, and 30-day outcomes associated with myocardial injury after noncardiac surgery (MINS) in vascular surgical patients. BACKGROUND: MINS has been independently associated with 30-day mortality after noncardiac surgery. The characteristics and prognostic importance of MINS in vascular surgery patients are poorly described. METHODS: This was an international prospective cohort study of 15,102 noncardiac surgery patients 45 years or older, of whom 502 patients underwent vascular surgery. All patients had fourth-generation plasma troponin T (TnT) concentrations measured during the first 3 postoperative days. MINS was defined as a TnT of 0.03 ng/mL of higher secondary to ischemia. The objectives of the present study were to determine (i) if MINS is prognostically important in vascular surgical patients, (ii) the clinical characteristics of vascular surgery patients with and without MINS, (iii) the 30-day outcomes for vascular surgery patients with and without MINS, and (iv) the proportion of MINS that probably would have gone undetected without routine troponin monitoring. RESULTS: The incidence of MINS in the vascular surgery patients was 19.1% (95% confidence interval (CI), 15.7%-22.6%). 30-day all-cause mortality in the vascular cohort was 12.5% (95% CI 7.3%-20.6%) in patients with MINS compared with 1.5% (95% CI 0.7%-3.2%) in patients without MINS (P < 0.001). MINS was independently associated with 30-day mortality in vascular patients (odds ratio, 9.48; 95% CI, 3.46-25.96). The 30-day mortality was similar in MINS patients with (15.0%; 95% CI, 7.1-29.1) and without an ischemic feature (12.2%; 95% CI, 5.3-25.5, P = 0.76). The proportion of vascular surgery patients who suffered MINS without overt evidence of myocardial ischemia was 74.1% (95% CI, 63.6-82.4). CONCLUSIONS: Approximately 1 in 5 patients experienced MINS after vascular surgery. MINS was independently associated with 30-day mortality. The majority of patients with MINS were asymptomatic and would have gone undetected without routine postoperative troponin measurement.

Isquemia Miocárdica/diagnóstico , Complicações Pós-Operatórias/diagnóstico , Troponina T/sangue , Procedimentos Cirúrgicos Vasculares , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/sangue , Isquemia Miocárdica/epidemiologia , Isquemia Miocárdica/etiologia , Razão de Chances , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/epidemiologia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos
Dev Dyn ; 247(3): 481-491, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28722313


Epithelial to mesenchymal transition (EMT) is a developmental program reactivated by tumor cells that leads to the switch from epithelial to mesenchymal phenotype. During EMT, cells are transcriptionally regulated to decrease E-cadherin expression while expressing mesenchymal markers such as vimentin, fibronectin, and N-cadherin. Growing body of evidences suggest that cells engaged in EMT undergo a metabolic reprograming process, redirecting glucose flux toward hexosamine biosynthesis pathway (HBP), which fuels aberrant glycosylation patterns that are extensively observed in cancer cells. HBP depends on nutrient availability to produce its end product UDP-GlcNAc, and for this reason is considered a metabolic sensor pathway. UDP-GlcNAc is the substrate used for the synthesis of major types of glycosylation, including O-GlcNAc and cell surface glycans. In general, the rate limiting enzyme of HBP, GFAT, is overexpressed in many cancer types that present EMT features as well as aberrant glycosylation. Moreover, altered levels of O-GlcNAcylation can modulate cell morphology and favor EMT. In this review, we summarize some of the current knowledge that correlates glucose metabolism, aberrant glycosylation and hyper O-GlcNAcylation supported by HBP that leads to EMT activation. Developmental Dynamics 247:481-491, 2018. © 2017 Wiley Periodicals, Inc.

Plasticidade Celular , Transição Epitelial-Mesenquimal , Redes e Vias Metabólicas , Animais , Glicosilação , Hexosaminas/biossíntese , Humanos
Vínculo ; 15(2): 82-91, jul.-dez. 2018.
Artigo em Português | LILACS, Index Psicologia - Periódicos técnico-científicos | ID: biblio-986212


Vivemos numa sociedade cada vez mais informatizada, sobrecarregada de estímulos e de exigências tecnológicas onde praticamente desde o nascimento que o ser humano tem contacto com estas interfaces. Perante esta realidade questionam-nos: onde fica o lugar do brincar, do simbólico, da criatividade e da intersubjetividade no desenvolvimento das crianças/adolescentes? Qual é o impacto que a tecnologia tem na criação da identidade das nossas crianças, de que forma se reflete na interação com os outros, nas suas escolhas? Qual o papel da Grupanálise e do Grupanalista nesta realidade?

We live in an increasingly computerized society, overwhelmed with stimuli and technological requirements where practically since the birth that the human being has contact with these interfaces. Faced with this reality we question: where is the place of play, symbolic, creativity and intersubjectivity in the development of children / adolescents? What is the impact that technology has on the creation of our children's identity, how is it reflected in the interaction with others, in their choices? What is the role of Group analysis and Group analyst in this reality?

Vivimos en una sociedad cada vez más informatizada, sobrecargada de estímulos y de exigencias tecnológicas donde prácticamente desde el nacimiento que el ser humano tiene contacto con estas interfaces. Ante esta realidad nos cuestionan: ¿dónde queda el lugar del juego, del simbólico, de la creatividad y de la intersubjetividad en el desarrollo de los niños / adolescentes? ¿Cuál es el impacto que la tecnología tiene en la creación de la identidad de nuestros niños, de qué forma se refleja en la interacción con los demás, en sus elecciones? ¿Cuál es el papel del Grupoanálisis y del Grupanalista en esta realidad?

Humanos , Masculino , Feminino , Criança , Adolescente , Psicoterapia de Grupo , Tecnologia
Oncotarget ; 8(61): 104136-104148, 2017 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-29262627


Primary liver cancers represent the second leading cause of cancer-related deaths worldwide. Diverse etiological factors include chronic viral hepatitis, aflatoxin and alcohol exposure as well as aberrant liver lipid overload. Cholesterol has been identified as a key inducer of metabolic impairment, oxidative stress and promoter of cellular dysfunction. The aim of this work was to address the oxidative stress-mediated DNA damage induced by cholesterol overload, and its role in the development of hepatocellular carcinoma. C57BL/6 male mice were fed with a high cholesterol diet, followed by a single dose of N-diethylnitrosamine (DEN, 10 µg/g, ip). Reactive oxygen species generation, DNA oxidation, antioxidant and DNA repair proteins were analyzed at different time points. Diet-induced cholesterol overload caused enhanced oxidative DNA damage in the liver and was associated with a decrease in key DNA repair genes as early as 7 days. Interestingly, we found a cell survival response, induced by cholesterol, judged by a decrement in Bax to Bcl2 ratio. Importantly, N-acetyl-cysteine supplementation significantly prevented DNA oxidation damage. Furthermore, at 8 months after DEN administration, tumor growth was significantly enhanced in mice under cholesterol diet in comparison to control animals. Together, these results suggest that cholesterol overload exerts an oxidative stress-mediated effects and promotes the development of liver cancer.

Future Sci OA ; 3(4): FSO245, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29134129


Aim: Carbapenems are antibiotics reserved for treatment of severe infections. Carbapenem antimicrobial susceptibility testing profiles were determined in a population of Klebsiella pneumoniae, and their resistance assessed based on previous and current Clinical and Laboratory Standards Institute criteria. Materials & methods: Isolates were examined using an automated antimicrobial susceptibility testing method, and real time polymerase chain reaction to detect the resistance (blaKPC) gene. Results: The prevalence of blaKPC gene was 45/54 (83.3%). Five isolates that were susceptible under the previous criteria changed to nonsusceptible with the current standards. The overall difference in susceptibility between the standards was 8%. Conclusion: This study shows that the current Clinical and Laboratory Standards Institute criteria may not offer additional benefits in the fight against carbapenem-resistant Enterobacteriaceae.

Conscientiae saúde (Impr.) ; 16(3): 375-384, set. 2017.
Artigo em Português | LILACS-Express | ID: biblio-881647


Introdução: A estimulação Transcraniana por corrente contínua (ETCC) é uma técnica neuromodulatória que pode alterar um padrão de excitabilidade mal adaptativo frente á uma lesão neurológica. Seu uso combinado com o treino motor vem sendo amplamente discutido na literatura. Objetivo: realizar uma revisão de estudos que utilizaram a ETCC combinada com treinos físicos de membros inferiores para melhora da marcha, equilíbrio e controle postural de pacientes neurológicos. Método: Foi realizada uma revisão bibliográfica nas bases de dados: Medline, Lilacs, Embase, Physiotherapy Evidence Database, Cochrane databases, Cinahl, Scielo e PubMed.Os artigos utilizados nesta revisão foram pontuados e qualificados através da escala Physiotherapy Evidence Database. Resultados:Foram incluídos no estudo 9 artigos combinando o uso da ETCC a treinos motores de membros inferiores. Conclusão: Os resultados dos estudos mostram que embora ainda não exista uma padronização dos parâmetros ideais de utilização da ETCC, sugerimos que seu uso combinado com treino motor pode potencializar os efeitos funcionais da terapia.

Background: Transcranial direct current stimulation (tDCS) is a neuromodulatory stimulation technique that can modulate a maladaptive excitation pattern against neurological injury. The combined use of this technique with physical rehabilitation has been widely discussed in the literature. Objective: To conduct a review of studies that employed the tDCS combined with lower limb training to improve gait, balance and postural control in neurological patients. Methods: A bibliographic review was performed in the databases: Medline, Lilacs, Embase, Physiotherapy Evidence Database, Cochrane databases, Cinahl, Scielo and PubMed.Selected articles were scored and qualified based on the Physiotherapy Evidence Database scale. Results: Nine studies involving the combination of tDCS and lower limb motor training for individuals with neurological problems were included. Conclusion: Despite being widely studied scientifically, no general consensus is yet found in the literature regarding the ideal tDCS administration parameters, we suggest that the combined use with motor training may potentiate the functional effects of therapy.

Rev. méd. hondur ; 85(1-2): 30-34, ene.-jun. 2017. ilus, tab
Artigo em Espanhol | LILACS | ID: biblio-884091


Antecedentes. La esclerosis sistémica sin esclerodermia es una variante rara de la esclerosis sistémica limitada en la que los pacientes no presentan manifestaciones cutáneas importantes. Caso clínico. Se presenta caso de paciente femenina en la sexta década de la vida sin antecedentes patológicos de importancia que presentaba Síndrome de Raynaud, fotosensibilidad y pares- tesias en manos; al examen físico estertores finos e induración leve de la piel de los dedos, se sospechaba enfermedad del colágeno y se realizaron exámenes de laboratorio que confirmaron diagnóstico de Esclerosis Sistémica sin esclerodermia, ya que presentaba mayores manifestaciones cardiopulmonares. Inició tratamiento con esteroides sistémicos pero se complicó con Neumonitis Intersticial tratada con Azatriopina e Hipertensión pulmonar manejada con Sildenafil. También se comenzó Rituximab, como terapia de artritis reumatoide diagnosticada posteriormente. Ha presentado leve mejoría en el patrón pulmonar restrictivo por lo que el tratamiento con Rituximab aún persiste. Paciente con buena evolución clínica y exámenes de laboratorio control dentro de los rangos normales, sin embargo función pulmonar continúa alterada, pero sin modificar actividades diarias. Conclusión: La caracterización de la enfermedad es vital, actualmente se cuenta con criterios diagnósticos más certeros para orientar el manejo adecuado dentro de una amplia gama de posibilidades terapéuticas...(AU)

Humanos , Feminino , Pessoa de Meia-Idade , Doenças Pulmonares Intersticiais , Doença Cardiopulmonar/complicações , Doença de Raynaud , Escleroderma Sistêmico/diagnóstico
Rev. bras. anestesiol ; 67(3): 288-293, Mar.-June 2017. tab
Artigo em Inglês | LILACS-Express | ID: biblio-843399


Abstract Background and objectives: Neuromuscular relaxants are essential during general anesthesia for several procedures. Classical anesthesiology literature indicates that the use of neuromuscular blockade in thoracic surgery may be deleterious in patients in lateral decubitus position in one-lung ventilation. The primary objective of our study was to compare respiratory function according to the degree of patient neuromuscular relaxation. Secondary, we wanted to check that neuromuscular blockade during one-lung ventilation is not deleterious. Methods: A prospective, longitudinal observational study was made in which each patient served as both treated subject and control. 76 consecutive patients programmed for lung resection surgery in Gregorio Marañon Hospital along 2013 who required one-lung ventilation in lateral decubitus were included. Ventilator data, hemodynamic parameters were registered in different moments according to train-of-four response (intense, deep and moderate blockade) during one-lung ventilation. Results: Peak, plateau and mean pressures were significantly lower during the intense and deep blockade. Besides compliance and peripheral oxygen saturation were significantly higher in that moments. Heart rate was significantly higher during deep blockade. No mechanical ventilation parameters were modified during measurements. Conclusions: Deep neuromuscular blockade attenuates the poor lung mechanics observed during one-lung ventilation.

Resumo Justificativa e objetivos: Os relaxantes neuromusculares são essenciais durante a anestesia geral para vários procedimentos. A literatura clássica de anestesiologia indica que o uso de bloqueio neuromuscular em cirurgia torácica pode ser prejudicial em pacientes posicionados em decúbito lateral com ventilação seletiva. O objetivo primário deste estudo foi comparar a função respiratória de acordo com o grau de relaxamento neuromuscular do paciente. O objetivo secundário foi verificar que o bloqueio neuromuscular durante a ventilação seletiva não é prejudicial. Métodos: Estudo observacional, prospectivo e longitudinal no qual cada paciente serviu como próprio controle. Foram incluídos 76 pacientes consecutivos, agendados para cirurgia de ressecção do pulmão no Hospital Gregorio Marañon ao longo de 2013, submetidos à ventilação seletiva em decúbito lateral. Os dados do ventilador e os parâmetros hemodinâmicos foram registrados em diferentes momentos de acordo com a resposta por sequência de quatro estímulos (bloqueio intenso, profundo e moderado) durante a ventilação seletiva. Resultados: As pressões de pico, platô e média foram significativamente menores durante os bloqueios intenso e profundo. Além disso, complacência e saturação periférica de oxigênio foram significativamente maiores nesses momentos. A frequência cardíaca foi significativamente maior durante o bloqueio profundo. Não houve alteração dos parâmetros da ventilação mecânica durante as mensurações. Conclusões: O bloqueio neuromuscular profundo atenua a mecânica pulmonar deficiente observada durante a ventilação seletiva.