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1.
J Exp Med ; 221(5)2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38557723

RESUMO

CD4+ T cells are vital for host defense and immune regulation. However, the fundamental role of CD4 itself remains enigmatic. We report seven patients aged 5-61 years from five families of four ancestries with autosomal recessive CD4 deficiency and a range of infections, including recalcitrant warts and Whipple's disease. All patients are homozygous for rare deleterious CD4 variants impacting expression of the canonical CD4 isoform. A shorter expressed isoform that interacts with LCK, but not HLA class II, is affected by only one variant. All patients lack CD4+ T cells and have increased numbers of TCRαß+CD4-CD8- T cells, which phenotypically and transcriptionally resemble conventional Th cells. Finally, patient CD4-CD8- αß T cells exhibit intact responses to HLA class II-restricted antigens and promote B cell differentiation in vitro. Thus, compensatory development of Th cells enables patients with inherited CD4 deficiency to acquire effective cellular and humoral immunity against an unexpectedly large range of pathogens. Nevertheless, CD4 is indispensable for protective immunity against at least human papillomaviruses and Trophyrema whipplei.


Assuntos
Linfócitos T CD4-Positivos , Linfócitos T Auxiliares-Indutores , Humanos , Linfócitos T CD8-Positivos , Ativação Linfocitária , Antígenos HLA , Isoformas de Proteínas/metabolismo
3.
Rev Med Inst Mex Seguro Soc ; 61(6): 747-758, 2023 Nov 06.
Artigo em Espanhol | MEDLINE | ID: mdl-37995301

RESUMO

Background: Describing the perception towards the online course on Primary Health Care (PHC) of the Institute of Health for Well-being (INSABI) will allow to establish improvement actions. Objective: Describe the factors that contribute to satisfaction with the PHC course offered online by INSABI. Material and methods: 620 records of the Health Education System for Well-being were studied. Satisfaction was determined using a Likert-type questionnaire with three dimensions: virtual environment, cognitive area, and measurement of learning. A deductive analysis of the open opinions was carried out. Results: 70% of the health personnel approved the course in less than a week, with an initial score of 5.41 ±1.9 points and final score of 7.8 ± 1.2. More than 65% had scores above the average in the three dimensions. Satisfaction with the virtual environment was 15.57 ± 3.4 points, and 15.73 ± 3.3 with the cognitive dimension. Age and gender were associated with dissatisfaction with the virtual environment and in the cognitive dimension, age was associated with dissatisfaction; 27.7% expressed negative comments, 28.5% related to course extension; 15.5% about the didactic techniques, 10.9% about the speakers and 10.4% about the final exam. Conclusions: The course generates significant learning, 62.4% of the students have a positive or neutral opinion. However, 27.8% expressed dissatisfaction, the majority related to the extension of the course.


Introducción: describir la percepción hacia el curso en línea de Atención Primaria de Salud (APS) del Instituto de Salud para el Bienestar (INSABI) permitirá establecer acciones de mejora. Objetivo: conocer el grado de satisfacción con el curso sobre APS que el INSABI ofrece en línea mediante un análisis mixto. Material y métodos: se estudiaron 620 registros del Sistema Educativo de Salud para el Bienestar. La satisfacción se determinó mediante un cuestionario tipo Likert con tres dimensiones: ambiente virtual, área cognitiva y medición del aprendizaje. Se realizó un análisis deductivo de las opiniones abiertas. Resultados: el 70% de los trabajadores de la salud aprobaron el curso en menos de una semana con una calificación inicial de 5.41 ± 1.9 puntos y la final de 7.8 ± 1.2. Más del 65% tuvieron puntuaciones por arriba de la media en las tres dimensiones. La satisfacción con el ambiente virtual fue de 15.57 ± 3.4 puntos, y de 15.73 ± 3.3 con la dimensión cognitiva. La edad y el sexo se asociaron a insatisfacción con el ambiente virtual y en la dimensión cognitiva, la edad se asoció con insatisfacción; el análisis cualitativo mostró que 27.7% expresaron comentarios negativos, 28.5% relacionadas con la extensión del curso; 15.5% sobre las técnicas didácticas, 10.9% acerca de los ponentes y 10.4% sobre el examen final. Conclusiones: el curso genera aprendizaje significativo, el 62.4% de los educandos tienen una opinión positiva o neutra. Sin embargo, 27.8% manifestaron insatisfacción, la mayoría relacionada con la extensión del curso.


Assuntos
Pessoal de Saúde , Estudantes , Humanos , Inquéritos e Questionários , Satisfação Pessoal , Atenção Primária à Saúde
4.
Heliyon ; 9(6): e16540, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37260897

RESUMO

The phenolic profile of Isabella grape (Vitis labrusca) offers beneficial properties to human health and makes it a functional food product. In order to better understand the phenolic compounds found in this grape variety and the biological effect they induce on breast cancer cells, an ultrasound-assisted extraction was carried out. During the extraction of polyphenols from Isabella grapes organically grown in Antioquia (Colombia), parameters such as frequency (33 kHz and 40 kHz), time and solvent were optimized to finally obtain a crude extract with antioxidant properties (Oxygen Radical Absorbance Capacity, ORAC: 293.22 ± 34.73 µmol of Trolox/g of sample), associated with a total polyphenol content (TPC) of 43.14 ± 5.00 mg GAE/g sample and a total anthocyanin content composed of 17.69 ± 2.59 mg of malvidin-3-glucoside/100 g of sample. MCF-7 breast cancer cells were treated with different concentrations of the optimized extract, and results show a decrease in cell viability related to mitochondrial membrane depolarization, ROS increase, and chromatin condensation. To determine the possible death induction mechanism, molecular docking was simulated to predict the molecular interactions between the most abundant phenolic compounds in Isabella grape and the main apoptosis-related proteins. The results obtained from in silico and in vitro experiments were consistent with each other, suggesting that the phenolic compounds found in Isabella grape can be considered potential adjuvant chemopreventive agents for the treatment of breast cancer.

5.
Rev Med Inst Mex Seguro Soc ; 61(3): 386-398, 2023 May 02.
Artigo em Espanhol | MEDLINE | ID: mdl-37216695

RESUMO

The Institute for Health for Well-being (INSABI according to its initials in Spanish), in collaboration with the National Institute of Medical Sciences and Nutrition Salvador Zubirán (INCMNSZ), instituted the Continuous Training on clinical management "Mexico against COVID-19" in 2020, with the purpose of training the frontline health personnel in the care for patients with COVID-19 in the context of hospital reconversion through the COVIDUTI platform. Virtual conferences were held for medical personnel from all over the country with the possibility of interacting with various specialists. In 2020, 215 sessions were held and 158 in 2021. That year educational content was expanded and included topics for other health categories, such as nursing and social work. In October 2021, it was established the Health Educational System for Well-being (SIESABI), with the aim of promoting continuous and permanent education for health workers. It currently offers face-to-face and virtual courses, permanent seminars, and telementoring, with the possibility of providing academic follow-up to its subscribers and linking priority courses that are on other platforms. The educational platform is an opportunity to unify the efforts of the health system in Mexico in the continuous and permanent education of professionals who care for people without social security and thereby contribute to the implementation of a model of care based on primary health care (PHC).


El Instituto de Salud para el Bienestar (INSABI), en colaboración con el Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ), instituyó el entrenamiento continuo sobre manejo clínico "México contra COVID-19" en 2020, con el propósito de capacitar al personal de salud de primera línea en la atención de pacientes con COVID-19 en el contexto de la reconversión hospitalaria mediante la plataforma COVIDUTI. Se realizaron conferencias virtuales dirigidas a personal médico de todo el país con la posibilidad de interactuar con diversos especialistas. En 2020 se realizaron 215 sesiones y 158 en 2021. Ese año se ampliaron contenidos educativos y se incluyeron temas para otras categorías de salud, como enfermería y trabajo social. En octubre de 2021 se estableció el Sistema Educativo de Salud para el Bienestar (SIESABI), con el objetivo de promover la educación continua y permanente para los trabajadores de la salud. Actualmente ofrece cursos presenciales, virtuales, seminarios permanentes y telementorías, con la posibilidad de dar seguimiento académico a sus suscriptores y vincular cursos prioritarios que están en otras plataformas. La plataforma educativa es una oportunidad para unificar los esfuerzos del sistema de salud en México en la educación continua y permanente de los profesionales que atienden a personas sin seguridad social y, con ello, contribuir en la implementación de un modelo de atención basado en Atención Primaria de Salud (APS).


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , Pessoal de Saúde/educação , Aprendizagem , México/epidemiologia
6.
Clin Colorectal Cancer ; 20(2): e100-e108, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33234431

RESUMO

BACKGROUND: The impact of sidedness in the high-risk stage II colorectal cancer (CRC) setting is uncertain. Although controversial, available data suggest a possible modest benefit of adjuvant chemotherapy (CT) in the adjuvant scenario. The aim of this study is to analyze the overall survival (OS) and recurrence-free survival (RFS) according to the tumor side. PATIENTS AND METHODS: In this single-center retrospective cohort, we analyzed patients treated between January 2011 and December 2018. We evaluated OS and RFS of high-risk patients according to the tumor side and considering adjuvant CT exposure and clinical and molecular features. RESULTS: A total of 1047 patients with stage II CRC were evaluated. Of these, 540 had high-risk criteria and microsatellite stability (MSS) or unknown status. One hundred fifty-seven (29%) patients had right-sided tumors, and 352 (65.2%) had left-sided tumors. Most patients received adjuvant CT, and the majority of them had T3 stage tumors, ≥ 12 lymph node resection, left tumor, MSS, and moderate differentiation. OS did not differ according to tumor side (5-year OS rates: 81.9% for right-sided tumors vs. 83% for left-sided tumors; hazard ratio, 0.91; 95% confidence interval, 0.55-1.53; P = .744). Adjuvant CT was associated with a superior RFS and OS, with 5-year OS rates of 87.7% versus 76.1% in the no-adjuvant group (hazard ratio, 0.46; 95% CI, 0.28-0.73; P = .001). CONCLUSION: The tumor side did not influence the outcomes in this study. Adjuvant CT was associated with improved RFS and OS in patients with high-risk stage II CRC, with a total gain of 11.6% in 5-year OS.


Assuntos
Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Adulto , Idoso , Quimioterapia Adjuvante , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos
7.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1177703

RESUMO

Introducción: Las manos de los trabajadores de la salud son los más frecuentes medios portadores de los microorganismos responsables de infecciones asociadas a la atención en salud. El objetivo de nuestro estudio fue evaluar el nivel de conocimientos de lavado de manos de tres hospitales nacionales del seguro social de salud en Lima metropolitana, 2018. Material y Métodos: Durante abril-agosto 2018, entrevistamos a enfermeras y médicos de tres hospitales nacionales con un cuestionario administrado en tres secciones y evaluado en escala vigesimal: generalidades, razones de la higiene de manos durante atención en salud y situaciones para realizar la higiene de manos. Resultados: La mediana del nivel de conocimientos de enfermeras y médicos sobre higiene de manos fue de 13,41. El nivel de conocimientos es diferente entre enfermeras y médicos (13,3 vs. 13,6). Asimismo, se encontraron menor frecuencia de acierto en los ítems: desinfección de manos dura 20 a 30 segundos (54,1%, n=276), desinfección de manos tiene 8 pasos (52,9%, n=270), eliminar los microorganismos transitorios de la piel (47,1%, n=240), cuando existe un diagnóstico infeccioso (34,7%, n=177). Conclusión: El nivel de conocimientos de las enfermeras y médicos fue bajo y existe diferencia entre subgrupos profesionales. Se recomienda implementar entrenamientos continuos siguiendo las estrategias multimodulares de la OMS


Introduction: The hands of health care workers are the most common means of carrying the microorganisms responsible for healthcare-associated infections. The objective of our study was to evaluate the level of handwashing knowledge in three national social health insurance hospitals in metropolitan Lima, 2018. Material and Methods: During April-August 2018, we interviewed nurses and physicians from three national hospitals with a three-sections questionnaire to evaluate on a twenty-first scale the following domains: generalities, reasons for hand hygiene during health care, and situations to perform hand hygiene. Results: The median knowledge of nurses and physicians about hand hygiene was 13.41. The knowledge differs between nurses and physicians (13.3 vs. 13.6). Also, there was a lower frequency of success in the following items: hand disinfection lasts 20 to 30 seconds (54.1%, n=276), hand disinfection has 8 steps (52.9%, n=270), elimination of transitory skin microorganisms (47.1%, n=240), when there is an infectious diagnosis (34.7%, n=177). Conclusion:The knowledge of nurses and physicians was low and there is a difference between professional subgroups. It is recommended to implement continuous training following the WHO multimodular strategies

8.
Clin Transl Immunology ; 9(5): e1130, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32355559

RESUMO

OBJECTIVE: Selective IgA deficiency (sIgAD) is the most common primary immunodeficiency in Western countries. Patients can suffer from recurrent infections and autoimmune diseases because of a largely unknown aetiology. To increase insights into the pathophysiology of the disease, we studied memory B and T cells and cytokine concentrations in peripheral blood. METHODS: We analysed 30 sIgAD patients (12 children, 18 adults) through detailed phenotyping of peripheral B-cell, CD8+ T-cell and CD4+ T-cell subsets, sequence analysis of IGA and IGG transcripts, in vitro B-cell activation and blood cytokine measurements. RESULTS: All patients had significantly decreased numbers of T-cell-dependent (TD; CD27+) and T-cell-independent (TI; CD27-) IgA memory B cells and increased CD21low B-cell numbers. IgM+IgD- memory B cells were decreased in children and normal in adult patients. IGA and IGG transcripts contained normal SHM levels. In sIgAD children, IGA transcripts more frequently used IGA2 than controls (58.5% vs. 25.1%), but not in adult patients. B-cell activation after in vitro stimulation was normal. However, adult sIgAD patients exhibited increased blood levels of TGF-ß1, BAFF and APRIL, whereas they had decreased Th1 and Th17 cell numbers. CONCLUSION: Impaired IgA memory formation in sIgAD patients is not due to a B-cell activation defect. Instead, decreased Th1 and Th17 cell numbers and high blood levels of BAFF, APRIL and TGF-ß1 might reflect disturbed regulation of IgA responses in vivo.These insights into B-cell extrinsic immune defects suggest the need for a broader immunological focus on genomics and functional analyses to unravel the pathogenesis of sIgAD.

9.
CES med ; 34(1): 64-73, ene.-abr. 2020. tab, graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1149157

RESUMO

Resumen La inmunoglobulina A (IgA) es el isotipo de anticuerpo más abundante en los humanos y fundamentalmente participa en la defensa contra las infecciones y el desarrollo de la tolerancia inmune en las mucosas. La deficiencia de IgA es la inmunodeficiencia más frecuente en humanos, pero comúnmente es asintomática y transitoria. Para diagnosticarla, se cuantifica la concentración de IgA en sangre y se evalúa la magnitud de su disminución. De acuerdo con esta evaluación se clasifica en deficiencia parcial (DPIgA) o deficiencia total (DTIgA). Adicionalmente, si solo se afectan los niveles de IgA sin alteraciones de otras inmunoglobulinas séricas como IgM e IgG o subclases de inmunoglobulina G, entonces se denomina como deficiencia selectiva de IgA (DSIgA). La deficiencia selectiva de IgA es de mayor relevancia clínica y considerada un error innato de la inmunidad, aunque su etiología aún es desconocida y clínicamente se asocia a infecciones de los tractos respiratorio y gastrointestinal, alergias y manifestaciones autoinmunes. Se realizó una búsqueda de artículos científicos en PubMed, Scopus, SciELO y Redalyc sobre la deficiencia selectiva de inmunoglobulina A, con el objetivo de realizar una revisión temática sobre las manifestaciones clínicas, el diagnóstico y el adecuado manejo clínico de los pacientes con esta inmunodeficiencia. Se propone un nuevo algoritmo clínico con el objetivo de mejorar el diagnóstico y brindar un adecuado manejo clínico de los pacientes con esta inmunodeficiencia. Un paciente con deficiencia selectiva de IgA se caracteriza por infecciones recurrentes de los tractos gastrointestinal y respiratorio, en asociación con manifestaciones alérgicas y autoinmunes en individuos mayores de cuatro años, con niveles de IgA sérica menores de 7 mg/dL y con niveles normales de IgG e IgM, y en quienes se hayan descartado defectos relacionados con los linfocitos T u otras causas de hipogammaglobulinemia. Con respecto al manejo clínico, se deben ajustar los esquemas de vacunación e implementar profilaxis antibiótica en las infecciones graves y recurrentes. Para mejorar el pronóstico se debe realizar una atención del paciente por un equipo médico interdisciplinario y un seguimiento continuo por un prolongado periodo de tiempo.


Abstract Immunoglobulin A (IgA) is the most abundant antibody isotype in humans and participates in protection against infections and the development of immune tolerance in mucous membranes. IgA deficiency is the most common immunodeficiency in humans, but it is commonly asymptomatic and transient. To diagnose it, the concentration of IgA in blood is quantified and the magnitude of its decrease is evaluated. According to this evaluation, it is classified as partial deficiency (DPIgA) or total deficiency (DTIgA). Additionally, if only IgA levels are affected without alterations in other serum immunoglobulins such as IgM and IgG or subclasses of IgG, then it is referred to as selective IgA deficiency (DSIgA). Selective IgA deficiency is of greater clinical relevance and considered an innate immunity error, although its etiology is still unknown. This immunodeficiency is clinically associated with respiratory and gas- trointestinal tract infections, allergies and autoimmune manifestations. A search of scientific articles was conducted in bibliographic databases PubMed, Scopus, SciELO and Redalyc on selective immunoglobulin A deficiency. Our objective was to perform a review on clinical manifestations, diagnosis, and appropriate clinical management of patients with this immunodeficiency. A new clinical algorithm is proposed in order to improve the diagnosis and provide adequate clinical management of patients with this immunodeficiency. A patient with selective IgA deficiency is characterized by recurrent infections of the gastrointestinal and respiratory tracts, in association with allergic and autoimmune manifestations in individuals older than four years. Serum IgA levels are less than 7 mg/dL, with normal levels of IgG and IgM, and defects related to T lymphocytes or other causes of hypogammaglobulinemia have been ruled out. Regarding clinical management, vaccination schedules should be adjusted and antibiotic prophylaxis should be implemented in severe and recurrent infections. Additionally, to improve prognosis, patient care should be performed by an interdisciplinary medical team and continuous monitoring for a prolonged period of time.

10.
J Food Biochem ; 43(6): e12680, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31353616

RESUMO

Two varieties of common beans (Phaseolus vulgaris L.), Bayo Victoria and Negro 8025, were evaluated to determine the effect on cellular viability and mechanisms involved in apoptosis pathways, using a cellular model with HT-29 cells. Aqueous methanolic (50:50) extracts from cooked beans were analyzed for phenolic composition, identifying greater diversity of phenolic compounds in Bayo Victoria extracts. However, Negro 8025 showed greater phenolic content and cytotoxicity effects at lower media inhibitory concentrations, and greater effectiveness to activate apoptotic pathways. Proteins related to the arrest of cell cycle were modulated by both bean cultivars. Qualitative analysis by HPLC-PAD and HPLC-MS systems of phenolic compounds in common bean extracts showed mainly hydroxybenzoic and hydroxycinnamic acids, flavonols, and monomeric flavan-3-ols. Bioactive phenolics such as catechin, kaempferol, and ferulic acid were found in both cultivars as well anticancer phytochemicals such as quercetin, protocatechuic acid, myricetin, naringenin and their derivatives, and procyanidins. PRACTICAL APPLICATIONS: Polyphenols in common beans (Phaseolus vulgaris L.) cultivars processed by canning display chemoprotective potential as they activate mechanisms involved in apoptosis pathways. Phenolics in common beans modulate 28 proteins related to apoptotic processes. Therefore, a diet including canned beans (particularly darker varieties) might represent health benefits and cancer-preventive effects.


Assuntos
Linhagem Celular Tumoral/efeitos dos fármacos , Phaseolus/química , Extratos Vegetais/farmacologia , Antioxidantes/análise , Apoptose , Cromatografia Líquida de Alta Pressão/métodos , Flavonóis/análise , Células HT29 , Humanos , Neoplasias/prevenção & controle , Fenóis/análise , Compostos Fitoquímicos/análise , Extratos Vegetais/análise , Polifenóis/análise , Sementes/química
11.
Rev. cuba. invest. bioméd ; 38(2): 226-237, abr.-jun. 2019. tab
Artigo em Espanhol | LILACS-Express | LILACS, CUMED | ID: biblio-1093402

RESUMO

Introducción: El fútbol es un deporte de varias acciones motrices, que provoca en el cuerpo un desequilibrio constante, enfatizado en edades tempranas, siendo a su vez la propiocepción una estrategia para potenciar el equilibrio en futbolistas de iniciación. Objetivo: Valorar los efectos de una intervención propioceptiva a corto plazo sobre el déficit de equilibrio en miembros inferiores de futbolistas infantiles. Métodos: Estudio cuasi-experimental de corte transversal a una población de 12 futbolistas infantiles (10-12 años), se aplicó un entrenamiento propioceptivo de cuatro semanas de duración enfatizando en aspectos específicos para potenciar el equilibrio corporal en su fase estática. Se valoraron tres variables para cada pie a partir de la aplicación del Y Balance Test en dos momentos de la preparación deportiva. Resultados: El test empleado determinó un nivel de significancia estadística: Pie Derecho Movimiento Izquierdo (p= 0,005), Pie Derecho Movimiento Central (p= 0,004), Pie Derecho Movimiento Derecho (p= 0,005), Pie Izquierdo Movimiento Izquierdo (p= 0,003), Pie Izquierdo Movimiento Central (p= 0,003), Pie Izquierdo Movimiento Derecho (p= 0,004). Conclusiones: Un entrenamiento propioceptivo a corto plazo es efectivo para mejorar significativamente el equilibrio estático en extremidades inferiores en futbolistas infantiles(AU)


Introduction: Soccer is a sport of several motor actions, which causes a constant imbalance in the body, emphasized at an early age, is the proprioception of a strategy to strengthen the balance in initiation players. Objective: To assess the effects of a short-term proprioceptive intervention on the balance deficit in lower limbs of child soccer players. Methods: Quasi-experimental cross-sectional study of a population of 12 child soccer players (10-12 years), a four-week proprioceptive training was applied, emphasizing specific aspects to enhance body balance in its static phase. Three variables were assessed for each foot from the application of the Y Balance Test in two moments of sports preparation. Results: The test used determined a level of statistical significance: Right Foot Left Movement (p= 0.005), Right Foot Central Movement (p= 0.004), Right Foot Right Movement (p= 0.005), Left Foot Left Movement (p= 0.003), Left Foot Central Movement (p= 0.003), Left Foot Right Movement (p= 0.004). Conclusions: Short-term proprioceptive training is effective in significantly improving the static balance in the lower extremities in child soccer players(AU)


Assuntos
Humanos , Criança , Propriocepção , Futebol , Estudos Transversais , Técnicas de Exercício e de Movimento/métodos , Equilíbrio Postural , Ensaios Clínicos Controlados não Aleatórios como Assunto , Tutoria/métodos
12.
Blood ; 134(2): 134-146, 2019 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-31076441

RESUMO

The inflammatory responsiveness of phagocytes to exogenous and endogenous stimuli is tightly regulated. This regulation plays an important role in systemic inflammatory response syndromes (SIRSs). In SIRSs, phagocytes initially develop a hyperinflammatory response, followed by a secondary state of hyporesponsiveness, a so-called "tolerance." This hyporesponsiveness can be induced by endotoxin stimulation of Toll-like receptor 4 (TLR4), resulting in an ameliorated response after subsequent restimulation. This modification of inflammatory response patterns has been described as innate immune memory. Interestingly, tolerance can also be triggered by endogenous TLR4 ligands, such as the alarmins myeloid-related protein 8 (MRP8, S100A8) and MRP14 (S100A9), under sterile conditions. However, signaling pathways that trigger hyporesponsiveness of phagocytes in clinically relevant diseases are only barely understood. Through our work, we have now identified 2 main signaling cascades that are activated during MRP-induced tolerance of phagocytes. We demonstrate that the phosphatidylinositol 3-kinase/AKT/GSK-3ß pathway interferes with NF-κB-driven gene expression and that inhibition of GSK-3ß mimics tolerance in vivo. Moreover, we identified interleukin-10-triggered activation of transcription factors STAT3 and BCL-3 as master regulators of MRP-induced tolerance. Accordingly, patients with dominant-negative STAT3 mutations show no tolerance development. In a clinically relevant condition of systemic sterile stress, cardiopulmonary bypass surgery, we confirmed the initial induction of MRP expression and the tolerance induction of monocytes associated with nuclear translocation of STAT3 and BCL-3 as relevant mechanisms. Our data indicate that the use of pharmacological JAK-STAT inhibitors may be promising targets for future therapeutic approaches to prevent complications associated with secondary hyporesponsiveness during SIRS.


Assuntos
Fagócitos/metabolismo , Transdução de Sinais/fisiologia , Síndrome de Resposta Inflamatória Sistêmica/metabolismo , Adulto , Alarminas/imunologia , Alarminas/metabolismo , Animais , Ponte Cardiopulmonar/efeitos adversos , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Fagócitos/imunologia , Síndrome de Resposta Inflamatória Sistêmica/imunologia , Adulto Jovem
14.
Artigo em Espanhol | LILACS, COLNAL | ID: biblio-970683

RESUMO

"Introducción: La voz es considerada una herramienta para la interacción y el desempeño de los seres humanos en una sociedad. Los docentes son considerados por la organización internacional del trabajo (OIT), el primer grupo en riesgo de presentar patologías vocales. Objetivo: Realizar una revisión de la literatura sobre la anatomía y fisiología de la voz, factores de riesgo y síntomas de los trastornos vocales, así como el contexto normativo bajo el cual se regula y las medidas de prevención necesarias para disminuir la prevalencia de estas patologías. Diseño: Revisión Narrativa de la literatura. Metodología: Se realizó una búsqueda de la literatura en bases de datos biomédicas y literatura gris, utilizando los términos MeSH, DeCS y términos naturales, entre los años 2000-2015. Con respecto a la legislación actual en enfermedades ocupacionales se realizó una búsqueda avanzada incluyendo los términos; normatividad, ley, salud ocupación y Colombia. Resultados: Se revisaron 75 artículos según los requerimientos de los objetivos. Se encontraron 6 leyes vigentes. El estado del arte reconoce la necesidad de la creación de programas enfocados en prevención y promoción primaria en docentes. Discusión: Debido al desempeño de su labor y a malos hábitos vocales, los docentes constituyen el conjunto de personas que más se acercan a la consulta de otorrinolaringología aquejándose de síntomas vocales. Sin embargo, no existen registros adecuados, debido a la desinformación que gira en torno a estas patologías. Conclusiones: La disfonía ocupacional deber ser abordada desde la prevención y promoción primaria, para disminuir la prevalencia de la patología vocal en docentes."


"Introduction: Voice is considered a tool for the interaction and performance of human beings in a society. Teachers are considered by the International Labor Organization (ILO), the first group at risk of developing vocal pathologies. Objectives: To carry out a review of the literature on the anatomy and physiology of voice, risk factors and symptoms of vocal disorders, as well as the normative context under which it is regulated and the prevention measures that are needed for reducing the prevalence of these pathologies. Design: Narrative review of the literature. Methodology: A literature search was performed on biomedical databases and gray literature, using MeSH, DeCS and natural terms between the years 2000-2015. Regarding to the search for current regulations on occupational diseases, an advanced search was conducted in Google including the terms; "normatividad", "ley", "salud ocupación" and "Colombia". Results: We reviewed 76 articles according to the requirements of the objectives. 6 laws were in force. The state of the art recognizes the need to create programs focused on the growth of primary prevention and promotion programs in teachers. Discussion: Teachers are the patients who with the highest frequency come to consultation of otorhinolaryngology complaining of vocal symptoms due to the performance of their work and bad vocal habits. However, there are no adequate records, because of the misinformation around these pathologies. Conclusions: Occupational dysphonia should be approached from primary prevention and promotion to reduce the prevalence of vocal pathology in teachers."


Assuntos
Humanos , Docentes , Fonação , Distúrbios da Voz
15.
J Clin Immunol ; 37(7): 732-738, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28865061

RESUMO

PURPOSE: Mendelian susceptibility to mycobacterial disease is a rare clinical condition characterized by a predisposition to infectious diseases caused by poorly virulent mycobacteria. Other infections such as salmonellosis and candidiasis are also reported. The purpose of this article is to describe a young boy affected with various infectious diseases caused by Mycobacterium tuberculosis complex, Salmonella sp, Klebsiella pneumonie, Citrobacter sp., and Candida sp, complicated with severe enteropathy and transient hypogammaglobulinemia. METHODS: We reviewed medical records and performed flow cytometry staining for lymphocyte populations, lymphocyte proliferation in response to PHA, and intracellular IFN-γ production in T cell PHA blasts in the patient and a healthy control. Sanger sequencing was used to confirm the genetic variants in the patient and relatives. RESULTS: Genetic analysis revealed a bi-allelic mutation in IL12RB1 (C291Y) resulting in complete IL-12Rß1 deficiency. Functional analysis demonstrated the lack of intracellular production of IFN-γ in CD3+ T lymphocytes from the patient in response to rhIL-12p70. CONCLUSIONS: To our knowledge, this is the third patient with MSMD due to IL-12Rß1 deficiency complicated with enteropathy and hypogammaglobulinemia and the first case of this disease to be described in Colombia.


Assuntos
Agamaglobulinemia/genética , Candidíase/genética , Enterite/genética , Infecções por Bactérias Gram-Negativas/genética , Receptores de Interleucina-12/deficiência , Receptores de Interleucina-12/genética , Agamaglobulinemia/tratamento farmacológico , Vacina BCG , Candidíase/tratamento farmacológico , Farmacorresistência Bacteriana , Enterite/tratamento farmacológico , Predisposição Genética para Doença , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Humanos , Lactente , Mutação , Mycobacterium tuberculosis
16.
Biomedica ; 32(1): 92-102, 2012.
Artigo em Espanhol | MEDLINE | ID: mdl-23235791

RESUMO

INTRODUCTION: Streptococcus pneumoniae is a major cause of morbi-mortality in early childhood and elderly. However, a test to measure the antibody responses after specific vaccination is not available in Colombia. OBJECTIVE: An immunoenzymatic test was standardized for the measurement of serum IgG levels against 10 serotypes of S. pneumoniae in response to the specific vaccination. MATERIAL AND METHODS: Capsular polysaccharides 1, 3, 4, 5, 6B, 9V, 14, 18, 19F, 23F of S. pneumoniae were used as antigens in a solid-phase ELISA. These responses were characterized in a randomized selected healthy individuals from a Colombian population. RESULTS: The reference and control sera showed great reactivity against all the polysaccharides evaluated, especially against polysaccharide 14 and 19F. The lowest reactivity in these two sera was observed against polysaccharide 3 and 4. Among the children evaluated, polysaccharide 5/19F showed the highes pre-vaccination reactivity, and polysaccharide 14/19F showed the highest post-vaccination reactivity. Among the adults, polysaccharides 14 and 19F showed the greatest reactivity pre- and post-vaccination. For all the polysaccharides (excepting polysaccharide 5), an inverse association among high polysaccharide-specific pre-vaccination- and the increase of post-vaccination-IgG levels was observed. CONCLUSION: This ELISA test reliably quantifies the serum levels of specific IgG against 10 serotypes of S. pneumoniae. According to the responses by healthy individuals, the current study validates parameters used internationally as an adequate the response to the 23-valent pneumococcal vaccine.


Assuntos
Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/imunologia , Cápsulas Bacterianas/imunologia , Ensaio de Imunoadsorção Enzimática/normas , Imunoglobulina G/sangue , Polissacarídeos Bacterianos/imunologia , Streptococcus pneumoniae/imunologia , Adulto , Anticorpos Antibacterianos/biossíntese , Anticorpos Antibacterianos/imunologia , Criança , Pré-Escolar , Feminino , Humanos , Imunoglobulina G/biossíntese , Imunoglobulina G/imunologia , Masculino , Pessoa de Meia-Idade , Vacinas Pneumocócicas/imunologia , Padrões de Referência , Reprodutibilidade dos Testes , Sorotipagem , Streptococcus pneumoniae/classificação , Adulto Jovem
17.
Biomédica (Bogotá) ; 32(1): 92-102, ene.-mar. 2012. graf
Artigo em Espanhol | LILACS | ID: lil-639815

RESUMO

Introducción. Streptococcus pneumoniae es causante de gran morbimortalidad en niños pequeños y ancianos. Sin embargo, en Colombia no está disponible una prueba que evalúe la respuesta humoral a la vacunación específica contra este microorganismo Objetivo. Estandarizar en Colombia un ensayo inmunoenzimático para evaluar los niveles séricos de anticuerpos IgG contra diez serotipos de S. pneumoniae en respuesta a la vacunación específica y caracterizar esta respuesta en individuos sanos de nuestra población. Materiales y métodos. Se hizo un ELISA en fase sólida utilizando como antígenos los polisacáridos capsulares 1, 3, 4, 5, 6B, 9V, 14, 18, 19F y 23F de S. pneumoniae. Resultados. Los sueros de referencia y control reaccionaron fuertemente contra los polisacáridos evaluados, especialmente contra 14 y 19F. En los cinco niños sanos evaluados, los polisacáridos 5 y 19F presentaron los mayores títulos antes de la vacunación. Antes de la vacunación en los niños, y antes y después de la vacunación en los adultos, los polisacáridos 14 y 19F reaccionaron fuertemente. Para todos los polisacáridos, excepto para el 5, existe una relación inversa entre títulos altos de anticuerpos IgG antes de la vacunación y la razón de incremento de los títulos después de la misma. Conclusión. Esta prueba ELISA cuantifica de forma confiable los niveles de IgG sérica contra diez serotipos de S. pneumoniae y, de acuerdo con los resultados obtenidos en individuos sanos de nuestra población, en este trabajo se validan los parámetros internacionales para considerar adecuada la respuesta a la vacuna 23-valente contra este microorganismo.


Introduction. Streptococcus pneumoniae is a major cause of morbi-mortality in early childhood and elderly. However, a test to measure the antibody responses after specific vaccination is not available in Colombia. Objective. An immunoenzymatic test was standardized for the measurement of serum IgG levels against 10 serotypes of S. pneumoniae in response to the specific vaccination. Material and methods. Capsular polysaccharides 1, 3, 4, 5, 6B, 9V, 14, 18, 19F, 23F of S. pneumoniae were used as antigens in a solid-phase ELISA. These responses were characterized in a randomized selected healthy individuals from a Colombian population. Results. The reference and control sera showed great reactivity against all the polysaccharides evaluated, especially against polysaccharide 14 and 19F. The lowest reactivity in these two sera was observed against polysaccharide 3 and 4. Among the children evaluated, polysaccharide 5/19F showed the highes pre-vaccination reactivity, and polysaccharide 14/19F showed the highest post-vaccination reactivity. Among the adults, polysaccharides 14 and 19F showed the greatest reactivity pre- and post-vaccination. For all the polysaccharides (excepting polysaccharide 5), an inverse association among high polysaccharide-specific pre-vaccination- and the increase of post-vaccination-IgG levels was observed. Conclusion. This ELISA test reliably quantifies the serum levels of specific IgG against 10 serotypes of S. pneumoniae. According to the responses by healthy individuals, the current study validates parameters used internationally as an adequate the response to the 23-valent pneumococcal vaccine.


Assuntos
Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/imunologia , Cápsulas Bacterianas/imunologia , Ensaio de Imunoadsorção Enzimática/normas , Imunoglobulina G/sangue , Polissacarídeos Bacterianos/imunologia , Streptococcus pneumoniae/imunologia , Anticorpos Antibacterianos/biossíntese , Anticorpos Antibacterianos/imunologia , Imunoglobulina G/biossíntese , Imunoglobulina G/imunologia , Vacinas Pneumocócicas/imunologia , Padrões de Referência , Reprodutibilidade dos Testes , Sorotipagem , Streptococcus pneumoniae/classificação
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