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1.
Eur J Dent Educ ; 27(4): 859-868, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36458893

RESUMEN

INTRODUCTION: Clinical reasoning is a core competence in health professions that impacts the ability to solve patients' health problems. Due to its relevance, it is necessary to identify difficulties arising from different sources that affect clinical reasoning development in students. The aim of this study was to explore a comprehensive approach to identify challenges for clinical reasoning development in undergraduate dental students and their potential solutions. METHODS: Mixed methods were used in four stages: (1) students and clinical teachers focus groups to identify challenges to clinical reasoning development; (2) literature review to explore potential solutions for these challenges; (3) Delphi technique for teacher consensus on pertinence and feasibility of solutions (1-5 scale); and (4) teachers' self-perception of their ability to implement the solutions. RESULTS: Three categories and seven subcategories of challenges were identified: (I) educational context factors influencing the clinical reasoning process; (II) teacher's role in clinical reasoning development; and (III) student factors influencing the clinical reasoning process. From 134 publications identified, 53 were selected for review, resulting in 10 potential solutions. Through two Delphi rounds, teachers rated the potential solutions very highly in terms of relevance (4.50-4.85) and feasibility (3.50-4.29). Finally, a prioritisation ranking of these solutions was generated using their scores for relevance, feasibility, and teachers' self-perception of their ability to implement them. CONCLUSIONS: The present comprehensive approach identified challenges for clinical reasoning development in dental students and their potential solutions, perceived as relevant and feasible by teachers, requiring further research and follow-up actions to address them.


Asunto(s)
Educación en Odontología , Estudiantes de Odontología , Humanos , Competencia Clínica , Razonamiento Clínico , Grupos Focales , Técnica Delphi
2.
Front Immunol ; 13: 1010257, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36341442

RESUMEN

Long after Trypanosoma cruzi infection, 40% of individuals develop a progressive chronic chagasic cardiomyopathy (CCC), with systolic dysfunction and arrhythmias. Since we previously showed IL-1ß mediates the development of systolic dysfunction and cardiac arrhythmias in diabetes mellitus and cardiorenal syndrome, and IL-1ß remains elevated in Chagas disease patients, here we tested the role of IL-1ß in CCC using a mouse model. Mice deficient in IL-1R expression (Il-1r-/- ) survived acute T. cruzi infection with greater parasitemia than controls but did not lose weight as wild-type (WT) did. At the chronic stage, WT presented prolonged ventricular repolarization intervals (QJ), while Il-1r-/- presented intervals like noninfected controls. Infected Il-1r-/- and WT did not differ in stroke volume (SV), the incidence of cardiac arrhythmias on electrocardiography (EKG), whole heart action potential duration (APD), or the incidence of triggered activity after S1-S2 protocol, which is a measure of susceptibility to cardiac arrhythmias. We also treated chronically infected WT mice with an IL-1R antagonist, anakinra. Treatment shortened the QJ interval but did not improve the SV or the incidence of cardiac arrhythmias on EKG. Anakinra failed to reduce triggered activity following the electrical extra-stimulation protocol. In conclusion, the absence of functional IL-1ß/IL-1R signaling did not prevent or reverse the decrease of SV or the incidence of cardiac arrhythmias induced by chronic T. cruzi infection, implying this is not a critical mechanism in generating or maintaining CCC. Since similar cardiac abnormalities were previously credited to IL-1ß signaling, ruling out this mechanism is important to discourage further attempts of IL-1ß blockade as a therapeutical measure.


Asunto(s)
Cardiomiopatías , Enfermedad de Chagas , Trypanosoma cruzi , Ratones , Animales , Trypanosoma cruzi/fisiología , Proteína Antagonista del Receptor de Interleucina 1/metabolismo , Ratones Endogámicos C57BL , Arritmias Cardíacas/etiología
3.
Int. j. cardiovasc. sci. (Impr.) ; 35(3): 410-418, May-June 2022. graf
Artículo en Inglés | LILACS | ID: biblio-1375650

RESUMEN

Abstract An acute respiratory syndrome caused by SARS-CoV2 was declared a pandemic by the World Health Organization. Current data in the world and in Brazil show that approximately 40% of patients who died have some type of cardiac comorbidity. There are also robust reports showing an increase in IL-6 / IL-1B / TNF-alpha and the presence of lymphopenia in patients with COVID-19. Our team and others have shown that increased cytokines are the link between arrhythmias/Left ventricular dysfunction and the immune system in different diseases. In addition, it has been well demonstrated that lymphopenia can not only be a good marker, but also a factor that causes heart failure. Thus, the present review focused on the role of the immune system upon the cardiac alterations observed in the SARS-CoV2 infection. Additionally, it was well described that SARS-CoV-2 is able to infect cardiac cells. Therefore, here it will be reviewed in deep.


Asunto(s)
Arritmias Cardíacas/complicaciones , SARS-CoV-2/patogenicidad , COVID-19/complicaciones , Insuficiencia Cardíaca/etiología , Miocardio/inmunología , Arritmias Cardíacas/fisiopatología , Citocinas , Citocinas/inmunología , Coronavirus/patogenicidad , Disfunción Ventricular Izquierda/fisiopatología , Miocitos Cardíacos/patología , Síndrome Respiratorio Agudo Grave , Insuficiencia Cardíaca/complicaciones , Linfopenia/complicaciones
6.
J Immunol ; 205(10): 2795-2805, 2020 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-33037139

RESUMEN

Hemolysis causes an increase of intravascular heme, oxidative damage, and inflammation in which macrophages play a critical role. In these cells, heme can act as a prototypical damage-associated molecular pattern, inducing TLR4-dependent cytokine production through the MyD88 pathway, independently of TRIF. Heme promotes reactive oxygen species (ROS) generation independently of TLR4. ROS and TNF production contribute to heme-induced necroptosis and inflammasome activation; however, the role of ROS in proinflammatory signaling and cytokine production remains unknown. In this study, we demonstrate that heme activates at least three signaling pathways that contribute to a robust MAPK phosphorylation and cytokine expression in mouse macrophages. Although heme did not induce a detectable Myddosome formation, the TLR4/MyD88 axis was important for phosphorylation of p38 and secretion of cytokines. ROS generation and spleen tyrosine kinase (Syk) activation induced by heme were critical for most proinflammatory signaling pathways, as the antioxidant N-acetyl-l-cysteine and a Syk inhibitor differentially blocked heme-induced ROS, MAPK phosphorylation, and cytokine production in macrophages. Early generated mitochondrial ROS induced by heme was Syk dependent, selectively promoted the phosphorylation of ERK1/2 without affecting JNK or p38, and contributed to CXCL1 and TNF production. Finally, lethality caused by sterile hemolysis in mice required TLR4, TNFR1, and mitochondrial ROS, supporting the rationale to target these pathways to mitigate tissue damage of hemolytic disorders.


Asunto(s)
Hemo/metabolismo , Hemólisis/inmunología , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/inmunología , Animales , Quimiocina CXCL1/metabolismo , Modelos Animales de Enfermedad , Humanos , Macrófagos/citología , Macrófagos/inmunología , Ratones , Ratones Noqueados , Mitocondrias/inmunología , Mitocondrias/metabolismo , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Fosforilación/inmunología , Receptores Tipo I de Factores de Necrosis Tumoral/genética , Receptores Tipo I de Factores de Necrosis Tumoral/metabolismo , Quinasa Syk/metabolismo , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo
7.
Medwave ; 20(4): e7916, 2020 Jun 01.
Artículo en Español | MEDLINE | ID: mdl-32678809

RESUMEN

INTRODUCTION: COVID-19 is a world public health problem due to its morbidity and mortality, especially in at-risk groups. The dental environment has a high risk of viral transmission; accordingly, this study aimed to identify recommendations based on the best available evidence for dental care during this pandemic. METHODS: We performed a search for scientific evidence published since 2002 to March 23th 2020 in electronic databases (MEDLINE/PubMed, EMBASE, Cochrane, and Epistemonikos) and the web pages of the American Dental Association, Centers for Disease Control and Prevention Oral Health, the Ministry of Health in Chile and scientific societies. RESULTS: We included nine published studies. The recommendations were the following: unrestricted use of personal protection elements, use of extraoral radiographic techniques, use of mouth rinses with 1% hydrogen peroxide or 0.2% iodine povidone, a four-hand technique with ongoing aspiration and the use of absorbable sutures. Furthermore, there is a consensus that non-urgent treatments should be postponed during periods of community transmission. CONCLUSIONS: Dental practitioners are exposed to a high risk of cross-infection, meaning they must implement recommendations based on the best available evidence to preserve the health of team members and the population they are caring for.


INTRODUCCIÓN: La enfermedad por coronavirus-19 (COVID-19) es un problema mundial de salud pública debido a su morbimortalidad, especialmente en grupos de riesgo. El entorno odontológico tiene un alto riesgo de transmisión viral, por ello el objetivo de este estudio fue identificar recomendaciones para la atención odontológica durante esta pandemia. MÉTODOS: Se realizó una búsqueda de evidencia científica publicada desde 2002 hasta el 23 de marzo de 2020 en bases de datos electrónicas (MEDLINE/PubMed, EMBASE, Cochrane y Epistemonikos) y en las páginas electrónicas de la Asociación Dental Americana, de Centers for Disease Control and Prevention Oral Health, del Ministerio de Salud de Chile y de sociedades científicas. RESULTADOS: Se incluyeron nueve artículos publicados, en los cuales se recomienda el uso irrestricto de elementos de protección personal, preferir técnicas radiográficas extraorales, uso de enjuagues bucales con peróxido de hidrógeno al 1% o povidona yodada al 0,2%, técnica a cuatro manos con aspiración constante y uso de suturas reabsorbibles. Además, existe consenso respecto a que durante los periodos de transmisión comunitaria se deben posponer los tratamientos odontológicos no urgentes. CONCLUSIONES: Debido al alto riesgo de infección cruzada que presentan los equipos odontológicos, deben implementarse recomendaciones basadas en la mejor evidencia disponible, con el fin de preservar la salud de los miembros del equipo y de la población a su cuidado.


Asunto(s)
Infecciones por Coronavirus/prevención & control , Infecciones por Coronavirus/transmisión , Atención Odontológica/normas , Transmisión de Enfermedad Infecciosa de Paciente a Profesional/prevención & control , Transmisión de Enfermedad Infecciosa de Profesional a Paciente/prevención & control , Pandemias/prevención & control , Neumonía Viral/prevención & control , Neumonía Viral/transmisión , COVID-19 , Humanos , Guías de Práctica Clínica como Asunto
8.
PLoS Pathog ; 16(7): e1008599, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32692767

RESUMEN

Heme oxygenase (HO-1) mediates the enzymatic cleavage of heme, a molecule with proinflammatory and prooxidant properties. HO-1 activity deeply impacts host capacity to tolerate infection through reduction of tissue damage or affecting resistance, the ability of the host to control pathogen loads. In this Review, we will discuss the contribution of HO-1 in different and complex protozoan infections, such as malaria, leishmaniasis, Chagas disease, and toxoplasmosis. The complexity of these infections and the pleiotropic effects of HO-1 constitute an interesting area of study and an opportunity for drug development.


Asunto(s)
Hemo-Oxigenasa 1/metabolismo , Infecciones por Protozoos/enzimología , Animales , Humanos , Tolerancia Inmunológica/fisiología
9.
Autops. Case Rep ; 10(1): 2020137, Jan.-Mar. 2020. ilus
Artículo en Inglés | LILACS | ID: biblio-1087663

RESUMEN

Actinomycosis is an uncommon, endogenous, and chronic infection with varied and nonspecific clinical features such as abdominal, pelvic or cervical masses, ulcerative lesions, abscesses, draining fistula, fibrosis, and constitutional symptoms. The disease ensues when the bacteria disrupt the mucosal barrier, invade, and spread throughout interfascial planes. Currently, the diagnosis of actinomycosis is challenging because of its very low frequency and depending on the clinical presentation it may masquerade malignancies. Therapy consists initially in intravenous penicillin, followed by an oral regimen that may be extended until a year of treatment. A timely diagnosis is crucial to avoid extensive therapeutic attempt as surgery. However, a biopsy or drainage of abscesses and fistula's tract may be required not only as a diagnostic procedure as part of the therapy. We report the case of a 72-year-old woman with an abdominal mass initially misdiagnosed as a liposarcoma. A second biopsy of a skin lesion of the abdominal wall made the diagnosis of actinomycosis, avoiding a major surgical procedure. The patient was treated with a long-term course of antibiotics with favorable outcome. Liposarcoma was ruled out after the patient's full recovery with antibiotics and the misdiagnosis was credit to the overconfidence on the immunohistochemical positivity to MDM2.


Asunto(s)
Humanos , Femenino , Anciano , Actinomicosis/diagnóstico , Abdomen/anomalías , Liposarcoma/diagnóstico , Diagnóstico Diferencial
10.
Autops Case Rep ; 10(1): e2020137, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32039066

RESUMEN

Actinomycosis is an uncommon, endogenous, and chronic infection with varied and nonspecific clinical features such as abdominal, pelvic or cervical masses, ulcerative lesions, abscesses, draining fistula, fibrosis, and constitutional symptoms. The disease ensues when the bacteria disrupt the mucosal barrier, invade, and spread throughout interfascial planes. Currently, the diagnosis of actinomycosis is challenging because of its very low frequency and depending on the clinical presentation it may masquerade malignancies. Therapy consists initially in intravenous penicillin, followed by an oral regimen that may be extended until a year of treatment. A timely diagnosis is crucial to avoid extensive therapeutic attempt as surgery. However, a biopsy or drainage of abscesses and fistula's tract may be required not only as a diagnostic procedure as part of the therapy. We report the case of a 72-year-old woman with an abdominal mass initially misdiagnosed as a liposarcoma. A second biopsy of a skin lesion of the abdominal wall made the diagnosis of actinomycosis, avoiding a major surgical procedure. The patient was treated with a long-term course of antibiotics with favorable outcome. Liposarcoma was ruled out after the patient's full recovery with antibiotics and the misdiagnosis was credit to the overconfidence on the immunohistochemical positivity to MDM2.

11.
Clin Rev Allergy Immunol ; 58(1): 15-24, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30680604

RESUMEN

Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine that participates in innate and adaptive immune responses. MIF contributes to the resistance against infection agents, but also to the cellular and tissue damage in infectious, autoimmune, and allergic diseases. In the past years, several studies demonstrated a critical role for MIF in the pathogenesis of type-2-mediated inflammation, including allergy and helminth infection. Atopic patients have increased MIF amounts in affected tissues, mainly produced by immune cells such as macrophages, Th2 cells, and eosinophils. Increased MIF mRNA and protein are found in activated Th2 cells, while eosinophils stock pre-formed MIF protein and secrete high amounts of MIF upon stimulation. In mouse models of allergic asthma, the lack of MIF causes an almost complete abrogation of the cardinal signs of the disease including mucus secretion, eosinophilic inflammation, and airway hyper-responsiveness. Additionally, blocking the expression of MIF in animal models leads to significant reduction of pathological signs of eosinophilic inflammation such as rhinitis, atopic dermatitis, eosinophilic esophagitis and helminth infection. A number of studies indicate that MIF is important in the effector phase of type-2 immune responses, while its contribution to Th2 differentiation and IgE production is not consensual. MIF has been found to intervene in different aspects of eosinophil physiology including differentiation, survival, activation, and migration. CD4+ T cells and eosinophils express CD74 and CXCR4, receptors able to signal upon MIF binding. Blockage of these receptors with neutralizing antibodies or small molecule antagonists also succeeds in reducing the signals of inflammation in experimental allergic models. Together, these studies demonstrate an important contribution of MIF on eosinophil biology and in the pathogenesis of allergic diseases and helminth infection.


Asunto(s)
Susceptibilidad a Enfermedades , Eosinófilos/inmunología , Eosinófilos/metabolismo , Inflamación/etiología , Inflamación/metabolismo , Oxidorreductasas Intramoleculares/genética , Oxidorreductasas Intramoleculares/metabolismo , Factores Inhibidores de la Migración de Macrófagos/genética , Factores Inhibidores de la Migración de Macrófagos/metabolismo , Animales , Biomarcadores , Médula Ósea/metabolismo , Médula Ósea/patología , Eosinófilos/patología , Interacciones Huésped-Parásitos , Interacciones Huésped-Patógeno , Humanos , Hipersensibilidad/etiología , Hipersensibilidad/metabolismo , Hipersensibilidad/patología , Inflamación/patología , Transducción de Señal
12.
Medwave ; 20(5)2020.
Artículo en Inglés, Español | LILACS | ID: biblio-1116901

RESUMEN

INTRODUCCIÓN: La enfermedad por coronavirus-19 (COVID-19) es un problema mundial de salud pública debido a su morbimortalidad, especialmente en grupos de riesgo. El entorno odontológico tiene un alto riesgo de transmisión viral, por ello el objetivo de este estudio fue identificar recomendaciones para la atención odontológica durante esta pandemia. MÉTODOS: Se realizó una búsqueda de evidencia científica publicada desde 2002 hasta el 23 de marzo de 2020 en bases de datos electrónicas (MEDLINE/PubMed, EMBASE, Cochrane y Epistemonikos) y en las páginas electrónicas de la Asociación Dental Americana, de Centers for Disease Control and Prevention Oral Health, del Ministerio de Salud de Chile y de sociedades científicas. RESULTADOS: Se incluyeron nueve artículos publicados, en los cuales se recomienda el uso irrestricto de elementos de protección personal, preferir técnicas radiográficas extraorales, uso de enjuagues bucales con peróxido de hidrógeno al 1% o povidona yodada al 0,2%, técnica a cuatro manos con aspiración constante y uso de suturas reabsorbibles. Además, existe consenso respecto a que durante los periodos de transmisión comunitaria se deben posponer los tratamientos odontológicos no urgentes. CONCLUSIONES: Debido al alto riesgo de infección cruzada que presentan los equipos odontológicos, deben implementarse recomendaciones basadas en la mejor evidencia disponible, con el fin de preservar la salud de los miembros del equipo y de la población a su cuidado.


INTRODUCTION: COVID-19 is a world public health problem due to its morbidity and mortality, especially in at-risk groups. The dental environment has a high risk of viral transmission; accordingly, this study aimed to identify recommendations based on the best available evidence for dental care during this pandemic. METHODS: We performed a search for scientific evidence published since 2002 to March 23th 2020 in electronic databases (MEDLINE/PubMed, EMBASE, Cochrane, and Epistemonikos) and the web pages of the American Dental Association, Centers for Disease Control and Prevention Oral Health, the Ministry of Health in Chile and scientific societies. RESULTS: We included nine published studies. The recommendations were the following: unrestricted use of personal protection elements, use of extraoral radiographic techniques, use of mouth rinses with 1% hydrogen peroxide or 0.2% iodine povidone, a four-hand technique with ongoing aspiration and the use of absorbable sutures. Furthermore, there is a consensus that non-urgent treatments should be postponed during periods of community transmission. CONCLUSIONS: Dental practitioners are exposed to a high risk of cross-infection, meaning they must implement recommendations based on the best available evidence to preserve the health of team members and the population they are caring for.


Asunto(s)
Humanos , Atención Odontológica/normas , Transmisión de Enfermedad Infecciosa de Profesional a Paciente/prevención & control , Transmisión de Enfermedad Infecciosa de Paciente a Profesional/prevención & control , Pandemias/prevención & control , COVID-19/prevención & control , COVID-19/transmisión , Guías de Práctica Clínica como Asunto
13.
Artículo en Inglés | MEDLINE | ID: mdl-31297344

RESUMEN

Leishmaniasis is an infectious disease caused by protozoans of the genus Leishmania. The macrophage is the resident cell in which the parasite replicates and it is important to identify new compounds that can aid in parasite elimination since the drugs used to treat leishmaniasis are toxic and present side effects. We have previously shown that treatment of Leishmania braziliensis-infected macrophages with DETC (Diethyldithiocarbamate) induces parasite killing, in vivo. Thus, the objective of this study was to further evaluate the effect of oxidants and antioxidants in L. braziliensis-infected macrophages, following treatment with either oxidizing Hydrogen Peroxide, Menadione, DETC, or antioxidant [NAC (N-Acetyl-Cyteine), Apocynin, and Tempol] compounds. We determined the percentage of infected macrophages and number of amastigotes. Promastigote survival was also evaluated. Both DETC (SOD-inhibitor) and Tempol (SOD-mimetic) decreased the percentage of infected cells and parasite load. Hydrogen peroxide did not interfere with parasite burden, while superoxide-generator Menadione had a reducing effect. On the other hand, NAC (GSH-replenisher) and Apocynin (NADPH-oxidase inhibitor) increased parasite burden. Tempol surfaces as an interesting candidate for the chemotherapy of CL with an IC50 of 0.66 ± 0.08 mM and selectivity index of 151. While it remains obscure how a SOD-mimetic may induce leishmanicidal effects, we suggest the possibility of developing Tempol-based topical applications for the treatment of cutaneous leishmaniasis caused by L. braziliensis.


Asunto(s)
Óxidos N-Cíclicos/farmacología , Leishmania braziliensis/efectos de los fármacos , Leishmaniasis Cutánea/tratamiento farmacológico , Macrófagos/efectos de los fármacos , Superóxido Dismutasa/farmacología , Acetofenonas/farmacología , Animales , Antioxidantes , Modelos Animales de Enfermedad , Ditiocarba , Quimioterapia/métodos , Femenino , Peróxido de Hidrógeno , Concentración 50 Inhibidora , Macrófagos/parasitología , Ratones , Ratones Endogámicos BALB C , Carga de Parásitos , Marcadores de Spin , Vitamina K 3/farmacología
14.
J Mol Cell Cardiol ; 131: 101-111, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-31029578

RESUMEN

AIMS: Cardiac arrhythmias are one of the most important remote complications after kidney injury. Renal ischemia reperfusion (I/R) is a major cause of acute renal injury predisposing to several remote dysfunctions, including cardiac electrical disturbance. Since IL-1ß production dependent on NLRP3 represents a link between tissue malfunctioning and cardiac arrhythmias, here we tested the hypothesis that longer ventricular repolarization and arrhythmias after renal I/R depend on this innate immunity sensor. METHODS AND RESULTS: Nlrp3-/- and Casp1-/- mice reacted to renal I/R with no increase in plasma IL-1ß, different from WT (wild-type) I/R. A prolonged QJ interval and an increased susceptibility to ventricular arrhythmias were found after I/R compared to Sham controls in wild-type mice at 15 days post-perfusion, but not in Nlrp3-/- or CASP1-/- I/R, indicating that the absence of NLRP3 or CASP1 totally prevented longer QJ interval after renal I/R. In contrast with WT mice, we found no renal atrophy and no renal dysfunction in Nlrp3-/- and Casp1-/- mice after renal I/R. Depletion of macrophages in vivo after I/R and a day before IL-1ß peak (at 7 days post-perfusion) totally prevented prolongation of QJ interval, suggesting that macrophages might participate as sensors of tissue injury. Moreover, treatment of I/R-WT mice with IL-1r antagonist (IL-1ra) from 8 to 15 days post perfusion did not interfere with renal function, but reversed QJ prolongation, prevented the increase in susceptibility to ventricular arrhythmias and rescued a close to normal duration and amplitude of calcium transient. CONCLUSION: Taken together, these results corroborate the hypothesis that IL-1ß is produced after sensing renal injury through NRLP3-CASP1, and IL-1ß on its turn triggers longer ventricular repolarization and increase susceptibility to cardiac arrhythmias. Still, they offer a therapeutic approach to treat cardiac arrhythmias that arise after renal I/R.


Asunto(s)
Arritmias Cardíacas/etiología , Arritmias Cardíacas/metabolismo , Interleucina-1beta/metabolismo , Enfermedades Renales/complicaciones , Enfermedades Renales/metabolismo , Daño por Reperfusión/complicaciones , Daño por Reperfusión/metabolismo , Animales , Caspasa 1/genética , Caspasa 1/metabolismo , Inmunidad Innata/fisiología , Enfermedades Renales/inmunología , Masculino , Ratones , Ratones Endogámicos C57BL , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Daño por Reperfusión/inmunología , Transducción de Señal/fisiología
15.
Shock ; 50(4): 483-492, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30216298

RESUMEN

Hemodynamic collapse and myocardial dysfunction are among the major causes of death in severe sepsis. The purpose of this study was to assess the role played by toll-like receptor 4 and by the NLRP3 inflammasome in the cardiac dysfunction that occurs after high-grade polymicrobial sepsis. We performed the colon ascendens stent peritonitis (CASP) surgery in Tlr4, Nlrp3, and caspase-1 mice. We also assessed for the first time the electrical heart function in the colon ascendens stent peritonitis (CASP) model. The QJ interval was increased in wild-type C57BL/6J mice after CASP when compared with sham controls, a result paralleled by an increase in the cardiac action potential (AP) duration (APD). The decreases in ejection fraction (EF), left ventricle end diastolic volume, stroke volume, and cardiac output found after CASP were similar among all groups of mice. Similar heart response was found when Nlrp3 mice were submitted to high-grade cecal ligation and puncture. Despite developing cardiac dysfunction similar to wild types after CASP, Nlrp3 mice had reduced circulating levels of interleukin (IL)-1ß, IL-6 and tumor necrosis factor-α. Our results demonstrate that the genetic ablation of Tlr4, Nlrp3, and caspase-1 does not prevent the cardiac dysfunction, despite preventing the increase in pro-inflammatory cytokines, indicating that these are not feasible targets to therapy in high-grade sepsis.


Asunto(s)
Caspasa 1/metabolismo , Colon/metabolismo , Cardiopatías/metabolismo , Interleucina-1beta/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Peritonitis/complicaciones , Peritonitis/metabolismo , Receptor Toll-Like 4/metabolismo , Animales , Ecocardiografía , Masculino , Ratones , Ratones Endogámicos C57BL , Función Ventricular Izquierda/fisiología
16.
Pesqui. prát. psicossociais ; 13(3): 1-16, set.-dez. 2018. tab
Artículo en Portugués | LILACS | ID: biblio-976363

RESUMEN

Este estudo busca compreender significados e saberes de adolescentes sobre direitos sexuais para subsidiar intervenções educativas emancipatórias nas escolas. Desenvolveu-se pesquisa de abordagem qualitativa, foram realizadas entrevistas individuais com 29 adolescentes de 15 a 18 anos, alunos do ensino médio de escola pública e utilizou-se análise de conteúdo para interpretação das informações em profundidade. A pesquisa revelou que há falhas e omissões entre o que se estabelece nas leis e sua efetivação no cotidiano dos adolescentes, com violações aos seus direitos sexuais, tais como poucas informações qualificadas sobre sexualidade, a falta da educação em sexualidade nas escolas para todos os alunos, além de serviços de saúde específicos que atendam às suas necessidades, o que afeta a saúde sexual. Intervenções educativas emancipatórias que considerem conhecimentos científicos e os saberes de adolescentes e o pleno exercício da cidadania sexual podem reduzir vulnerabilidades relacionadas à saúde sexual e gerar transformações na realidade.


This study aims to understand the meanings and knowledge of adolescents about sexual rights to subsidize educational emancipatory interventions in schools. Qualitative approach research was developed, individual interviews were conducted with 29 adolescents aged 15 to 18, high school students from public schools, and content analysis was used to interpret the information in depth. The research revealed that there are flaws and omissions between what is established in the laws and their effectiveness in the daily life of adolescents, with violations of their sexual rights, such as few qualified information about sexuality, lack of sexuality education in schools for all students, besides Of specific health services that meet their needs, which affects sexual health. Emancipatory educational interventions that consider scientific knowledge and the knowledge of adolescents with the full exercise of sexual citizenship can reduce vulnerabilities related to sexual health and generate transformations in reality.


Este estudio busca comprender significados y saberes de adolescentes sobre derechos sexuales para subsidiar intervenciones educativas emancipatorias en las escuelas. Se desarrolló investigación de abordaje cualitativo, se realizaron entrevistas individuales con 29 adolescentes de 15 a 18 años, estudiantes de la Enseñanza Media de escuela pública, se utilizó análisis de contenido para interpretación de las informaciones en profundidad. La investigación reveló que hay fallas y omisiones entre lo que se establece en las leyes y su efectividad en el cotidiano de los adolescentes, con violaciones a sus derechos sexuales, tales como pocas informaciones calificadas sobre sexualidad, falta educación en sexualidad en las escuelas para todos los alumnos, además de servicios de salud específicos que atiendan a sus necesidades, lo que afecta la salud sexual. Las intervenciones educativas emancipatorias que consideren conocimientos científicos y los saberes de adolescentes con el pleno ejercicio de la ciudadanía sexual pueden reducir vulnerabilidades relacionadas con la salud sexual y generar transformaciones en la realidad.


Asunto(s)
Adolescente , Derechos Sexuales y Reproductivos , Educación Sexual , Problemas Sociales , Educación en Salud , Conducta del Adolescente , Servicios de Salud del Adolescente , Salud Sexual
17.
PLoS Pathog ; 14(4): e1006928, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29672619

RESUMEN

The activation of macrophage respiratory burst in response to infection with Trypanosoma cruzi inflicts oxidative damage to the host's tissues. For decades, the role of reactive oxygen species (ROS) in the elimination of T. cruzi was taken for granted, but recent evidence suggests parasite growth is stimulated in oxidative environments. It is still a matter of debate whether indeed oxidative environments provide ideal conditions (e.g., iron availability in macrophages) for T. cruzi growth and whether indeed ROS signals directly to stimulate growth. Nitric oxide (NO) and ROS combine to form peroxynitrite, participating in the killing of phagocytosed parasites by activated macrophages. In response to infection, mitochondrial ROS are produced by cardiomyocytes. They contribute to oxidative damage that persists at the chronic stage of infection and is involved in functional impairment of the heart. In this review, we discuss how oxidative stress helps parasite growth during the acute stage and how it participates in the development of cardiomyopathy at the chronic stage.


Asunto(s)
Enfermedad de Chagas/complicaciones , Cardiopatías/etiología , Macrófagos/microbiología , Estrés Oxidativo , Especies Reactivas de Oxígeno/metabolismo , Trypanosoma cruzi/patogenicidad , Animales , Enfermedad de Chagas/microbiología , Humanos
18.
Saúde debate ; 41(113): 658-669, Abr.-Jun. 2017.
Artículo en Portugués | LILACS | ID: biblio-903895

RESUMEN

RESUMO Este artigo apresenta uma experiência de educação em saúde conduzida por pesquisadores e estudantes do Ensino Médio de uma escola pública de Belo Horizonte (MG). Demonstra como problematizar direitos humanos, saúde e cidadania sexual, contextualizada à realidade de adolescentes. Evidenciou-se que a precariedade da vida, iniquidades de gênero, silenciamentos, negação de direitos sexuais, informações qualificadas insuficientes afetam a saúde sexual de adolescentes. O diálogo de saberes entre pesquisadores e adolescentes sobre direitos sexuais interfere positivamente na promoção da saúde sexual. Este relato pode contribuir para o planejamento de atividades na atenção primária para a promoção de saúde.


ABSTRACT This article presents an experience of health education conducted by researchers and High School students of a public school in Belo Horizonte (MG). It demonstrates how to problematize human rights, health and sexual citizenship, contextualized to the reality of adolescents. It has been emphasized that precariousness of life, gender inequities, silencing, denial of sexual rights, insufficient qualified information affect the sexual health of adolescents. The dialogue of knowledge between researchers and adolescents about sexual rights interferes positively in the promotion of sexual health. This report may contribute to the planning of activities in primary attention, for health promotion.

19.
Int J Cardiol ; 240: 354-359, 2017 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-28320606

RESUMEN

BACKGROUND: Cardiac arrhythmias are one of the main causes of death in ChCP and other dilated cardiomyopathies. Previous studies demonstrated that ventricular arrhythmias are associated with the presence of autoantibodies with beta-adrenergic activity, Ab-ß. OBJECTIVES: The aim of this study was to investigate whether Ab-ß, present in chronic chagasic patients (ChCP), induce cardiac arrhythmias in the pharmacological type-2 long QT syndrome model (LQTS-2). METHODS/RESULTS: The LQTS2 was established by perfusion of Tyrode saline solution with a potassium channel blocker E-4031 (5µM) in isolated rabbit hearts or in rabbit cardiac strips, in order to record ECG or action potential, respectively. Autoantibodies from ChCP activating (Ab-ß) or not (Ab-NR) cardiac beta 1-adrenergic receptors were used. Ab-ß, but not Ab-NR, were able to significantly shorten QT, QTc and increase Tpeak-Tend interval in the LQTS-2. A positive correlation between higher QTc and Tpeak-Tend was found after Ab-ß perfusion in the same model. In addition, in the LQTS-2 model, in almost 75% (11/15) of the hearts perfused with Ab-ß, ventricular and atrio-ventricular electrical disturbances were observed. Atenolol abolished all Ab-ß-induced arrhythmias. Ab-ß, when perfused in a cellular LQTS-2, drastically reduced the action potential duration and evoked early afterdepolarization (EAD's), while Ab-NR did not modulate the AP properties in the LQTS-2. CONCLUSION: The results indicate that Ab-ß were able to induce cardiac arrhythmias and EAD's. This phenomenon can explain, at least in part, the cellular mechanism of Ab-ß-induced arrhythmias. Furthermore, atenolol is effective for the treatment of Ab-ß-induced arrhythmias.


Asunto(s)
Arritmias Cardíacas/sangre , Arritmias Cardíacas/fisiopatología , Autoanticuerpos/sangre , Cardiomiopatía Chagásica/sangre , Síndrome de QT Prolongado/fisiopatología , Receptores Adrenérgicos beta 1/sangre , Potenciales de Acción/efectos de los fármacos , Potenciales de Acción/fisiología , Animales , Antiarrítmicos/farmacología , Antiarrítmicos/uso terapéutico , Antiarrítmicos/toxicidad , Arritmias Cardíacas/etiología , Electrocardiografía/efectos de los fármacos , Electrocardiografía/métodos , Corazón/efectos de los fármacos , Corazón/fisiopatología , Humanos , Síndrome de QT Prolongado/inducido químicamente , Estudios Longitudinales , Masculino , Conejos , Estudios Retrospectivos
20.
Nat Commun ; 7: 13344, 2016 11 24.
Artículo en Inglés | MEDLINE | ID: mdl-27882934

RESUMEN

Diabetes mellitus (DM) encompasses a multitude of secondary disorders, including heart disease. One of the most frequent and potentially life threatening disorders of DM-induced heart disease is ventricular tachycardia (VT). Here we show that toll-like receptor 2 (TLR2) and NLRP3 inflammasome activation in cardiac macrophages mediate the production of IL-1ß in DM mice. IL-1ß causes prolongation of the action potential duration, induces a decrease in potassium current and an increase in calcium sparks in cardiomyocytes, which are changes that underlie arrhythmia propensity. IL-1ß-induced spontaneous contractile events are associated with CaMKII oxidation and phosphorylation. We further show that DM-induced arrhythmias can be successfully treated by inhibiting the IL-1ß axis with either IL-1 receptor antagonist or by inhibiting the NLRP3 inflammasome. Our results establish IL-1ß as an inflammatory connection between metabolic dysfunction and arrhythmias in DM.


Asunto(s)
Diabetes Mellitus Experimental/inmunología , Interleucina-1beta/inmunología , Macrófagos/inmunología , Miocitos Cardíacos/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/inmunología , Taquicardia Ventricular/inmunología , Receptor Toll-Like 2/inmunología , Potenciales de Acción , Animales , Antirreumáticos/farmacología , Arritmias Cardíacas/etiología , Arritmias Cardíacas/inmunología , Arritmias Cardíacas/metabolismo , Calcio/metabolismo , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Caspasa 1/metabolismo , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/metabolismo , Inflamasomas/antagonistas & inhibidores , Proteína Antagonista del Receptor de Interleucina 1/farmacología , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Ratones , Ratones Transgénicos , Contracción Miocárdica , Miocitos Cardíacos/inmunología , Proteína con Dominio Pirina 3 de la Familia NLR/antagonistas & inhibidores , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Potasio/metabolismo , Receptores de Interleucina-1/antagonistas & inhibidores , Receptores de Interleucina-1/genética , Receptores de Interleucina-1/inmunología , Taquicardia Ventricular/etiología , Taquicardia Ventricular/metabolismo , Receptor Toll-Like 2/genética
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