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1.
J Neurochem ; 168(9): 3268-3283, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39126680

RESUMO

Dynamins are large GTPases whose primary function is not only to catalyze membrane scission during endocytosis but also to modulate other cellular processes, such as actin polymerization and vesicle trafficking. Recently, we reported that centronuclear myopathy associated dynamin-2 mutations, p.A618T, and p.S619L, impair Ca2+-induced exocytosis of the glucose transporter GLUT4 containing vesicles in immortalized human myoblasts. As exocytosis and endocytosis occur within rapid timescales, here we applied high-temporal resolution techniques, such as patch-clamp capacitance measurements and carbon-fiber amperometry to assess the effects of these mutations on these two cellular processes, using bovine chromaffin cells as a study model. We found that the expression of any of these dynamin-2 mutants inhibits a dynamin and F-actin-dependent form of fast endocytosis triggered by single action potential stimulus, as well as inhibits a slow compensatory endocytosis induced by 500 ms square depolarization. Both dynamin-2 mutants further reduced the exocytosis induced by 500 ms depolarizations, and the frequency of release events and the recruitment of neuropeptide Y (NPY)-labeled vesicles to the cell cortex after stimulation of nicotinic acetylcholine receptors with 1,1-dimethyl-4-phenyl piperazine iodide (DMPP). They also provoked a significant decrease in the Ca2+-induced formation of new actin filaments in permeabilized chromaffin cells. In summary, our results indicate that the centronuclear myopathy (CNM)-linked p.A618T and p.S619L mutations in dynamin-2 affect exocytosis and endocytosis, being the disruption of F-actin dynamics a possible explanation for these results. These impaired cellular processes might underlie the pathogenic mechanisms associated with these mutations.


Assuntos
Células Cromafins , Dinamina II , Endocitose , Exocitose , Mutação , Miopatias Congênitas Estruturais , Células Cromafins/metabolismo , Endocitose/fisiologia , Endocitose/genética , Dinamina II/genética , Dinamina II/metabolismo , Animais , Exocitose/fisiologia , Miopatias Congênitas Estruturais/genética , Miopatias Congênitas Estruturais/patologia , Miopatias Congênitas Estruturais/metabolismo , Mutação/genética , Bovinos , Humanos , Actinas/metabolismo , Actinas/genética , Células Cultivadas , Técnicas de Patch-Clamp , Glândulas Suprarrenais/metabolismo , Glândulas Suprarrenais/patologia
2.
Br J Pharmacol ; 181(16): 2905-2922, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38679932

RESUMO

BACKGROUND AND PURPOSE: ATP is highly accumulated in secretory vesicles and secreted upon exocytosis from neurons and endocrine cells. In adrenal chromaffin granules, intraluminal ATP reaches concentrations over 100 mM. However, how these large amounts of ATP contribute to exocytosis has not been investigated. EXPERIMENTAL APPROACH: Exocytotic events in bovine and mouse adrenal chromaffin cells were measured with single cell amperometry. Cytosolic Ca2+ measurements were carried out in Fluo-4 loaded cells. Submembrane Ca2+ was examined in PC12 cells transfected with a membrane-tethered Ca2+ indicator Lck-GCaMP3. ATP release was measured using the luciferin/luciferase assay. Knockdown of P2X7 receptors was induced with short interfering RNA (siRNA). Direct Ca2+ influx through this receptor was measured using a P2X7 receptor-GCamp6 construct. KEY RESULTS: ATP induced exocytosis in chromaffin cells, whereas the ectonucleotidase apyrase reduced the release events induced by the nicotinic agonist dimethylphenylpiperazinium (DMPP), high KCl, or ionomycin. The purinergic agonist BzATP also promoted a secretory response that was dependent on extracellular Ca2+. A740003, a P2X7 receptor antagonist, abolished secretory responses of these secretagogues. Exocytosis was also diminished in chromaffin cells when P2X7 receptors were silenced using siRNAs and in cells of P2X7 receptor knockout mice. In PC12 cells, DMPP induced ATP release, triggering Ca2+ influx through P2X7 receptors. Furthermore, BzATP, DMPP, and KCl allowed the formation of submembrane Ca2+ microdomains inhibited by A740003. CONCLUSION AND IMPLICATIONS: Autocrine activation of P2X7 receptors constitutes a crucial feedback system that amplifies the secretion of catecholamines in chromaffin cells by favouring submembrane Ca2+ microdomains.


Assuntos
Trifosfato de Adenosina , Catecolaminas , Células Cromafins , Exocitose , Receptores Purinérgicos P2X7 , Animais , Receptores Purinérgicos P2X7/metabolismo , Células Cromafins/metabolismo , Células Cromafins/efeitos dos fármacos , Bovinos , Trifosfato de Adenosina/metabolismo , Camundongos , Catecolaminas/metabolismo , Exocitose/efeitos dos fármacos , Células PC12 , Ratos , Cálcio/metabolismo , Comunicação Autócrina , Camundongos Endogâmicos C57BL , Células Cultivadas , Masculino
3.
Respirar (Ciudad Autón. B. Aires) ; 15(3): [157-167], sept. 2023.
Artigo em Espanhol | LILACS, UNISALUD, BINACIS | ID: biblio-1510520

RESUMO

Introducción: la fibrosis pulmonar idiopática (FPI) es una enfermedad progresiva y cró-nica con muy mal pronóstico. Actualmente, existen dos fármacos para esta patología. El propósito de nuestro estudio es evaluar los efectos del tratamiento en los pacientes de una consulta en vida real.


Introduction: idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease with a very poor prognosis. Two drugs are currently available for this disease. The purpo-se of our study is to evaluate the effects of treatment in patients in a real-life practice.


Assuntos
Humanos , Masculino , Feminino , Idoso , Dispneia , Fibrose Pulmonar Idiopática/tratamento farmacológico , Antifibróticos/uso terapêutico , Testes de Função Respiratória , Eficácia , Tolerância a Medicamentos
4.
Neuropathol Appl Neurobiol ; 49(4): e12918, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37317811

RESUMO

AIMS: Dynamin-2 is a large GTPase, a member of the dynamin superfamily that regulates membrane remodelling and cytoskeleton dynamics. Mutations in the dynamin-2 gene (DNM2) cause autosomal dominant centronuclear myopathy (CNM), a congenital neuromuscular disorder characterised by progressive weakness and atrophy of the skeletal muscles. Cognitive defects have been reported in some DNM2-linked CNM patients suggesting that these mutations can also affect the central nervous system (CNS). Here we studied how a dynamin-2 CNM-causing mutation influences the CNS function. METHODS: Heterozygous mice harbouring the p.R465W mutation in the dynamin-2 gene (HTZ), the most common causing autosomal dominant CNM, were used as disease model. We evaluated dendritic arborisation and spine density in hippocampal cultured neurons, analysed excitatory synaptic transmission by electrophysiological field recordings in hippocampal slices, and evaluated cognitive function by performing behavioural tests. RESULTS: HTZ hippocampal neurons exhibited reduced dendritic arborisation and lower spine density than WT neurons, which was reversed by transfecting an interference RNA against the dynamin-2 mutant allele. Additionally, HTZ mice showed defective hippocampal excitatory synaptic transmission and reduced recognition memory compared to the WT condition. CONCLUSION: Our findings suggest that the dynamin-2 p.R465W mutation perturbs the synaptic and cognitive function in a CNM mouse model and support the idea that this GTPase plays a key role in regulating neuronal morphology and excitatory synaptic transmission in the hippocampus.


Assuntos
Dinamina II , Miopatias Congênitas Estruturais , Animais , Camundongos , Modelos Animais de Doenças , Dinamina II/genética , Dinamina II/metabolismo , Músculo Esquelético/metabolismo , Mutação , Miopatias Congênitas Estruturais/genética , Neurônios/metabolismo , Transmissão Sináptica
5.
Rev. odontopediatr. latinoam ; 13: 224557, 2023. ilus
Artigo em Espanhol | LILACS, COLNAL | ID: biblio-1551961

RESUMO

El mesiodens es un diente supernumerario que se encuentra en la zona de los incisivos centrales superiores, cuyo diagnóstico temprano es fundamental ya que permite la extracción oportuna del mismo previniendo posibles alteraciones a futuro como son: el desarrollo de quistes, malposición de los dientes adyacentes, retraso de erupción, diastema interincisal, reabsorción apical de dientes vecinos. Reporte de caso: Paciente masculino, de 6 años con 11 meses de edad, que presentó mesiodens doble, cuyo hallazgo fue radiológico, mediante una panorámica, requisito de la odontóloga para control odontológico general, en el cual se pudo observar la presencia de dos dientes supernumerarios, los cuales estaban provocando la rotación de los incisivos permanentes superiores. El tratamiento se basó en la extracción quirúrgica temprana de los dientes supernumerarios, para determinar el abordaje fue necesario la realización de un estudio tomográfico, una vez determinada el proceso de extracción, y posteriormente la recuperación del paciente, y seguimiento radiográfico y clínico, se logró la erupción adecuada de los incisivos centrales superiores permanentes, hasta la actualidad se realizan controles periódicos y la colocación de placas de expansión superior e inferior. Conclusión: En este caso el tratamiento es la extracción temprana, y debido al diagnóstico oportuno y las condiciones óptimas del paciente como son: la reabsorción radicular fisiológica de los dientes primarios, la ubicación de los dientes supernumerarios, así como el estadio de Nolla de los incisivos centrales superiores, permite que el tratamiento elegido sea el óptimo y con las condiciones menos traumáticas posibles.


O mesiodens é um dente supranumerário encontrado na região dos incisivos centrais superiores, cuja detecção pode ser acidental. O diagnóstico precoce é fundamental, pois permite a extração oportuna do dente supranumerário, prevenindo possíveis alterações futuras como: desenvolvimento de cistos, má localização dos dentes adjacentes, atraso na erupção, diastema interincisal, reabsorção apical dos dentes vizinhos. Relato de caso: O caso apresentado é de um paciente pediátrico do sexo masculino, 6 anos e 11 meses, que apresentava duplo mesiodens, cujo achado foi radiológico, através de visão panorâmica, uma solicitação do cirurgião-dentista para controle odontológico geral, no qual pôde observar a presença de dois dentes supranumerários, que causavam a rotação dos incisivos permanentes superiores. O tratamento baseou-se na extração cirúrgica precoce dos dentes supranumerários, para determinar a abordagem foi necessário realizar um estudo tomográfico, uma vez determinado o processo de extração, e posteriormente a recuperação do paciente, e acompanhamento radiográfico e clínico , conseguiu-se uma erupção adequada dos incisivos centrais superiores permanentes, até o momento são realizadas verificações periódicas e colocação de placas de expansão superiores e inferiores. Conclusão: Neste caso, o tratamento é a extração precoce e devido ao diagnóstico oportuno e condições ideais do paciente, como: reabsorção radicular fisiológica dos dentes decíduos, localização dos dentes supranumerários, bem como o estágio Nolla dos dentes. incisivos centrais superiores, permite que o tratamento escolhido seja ótimo e com as condições menos traumáticas possíveis


Mesiodens is a supernumerary tooth found in the area of the upper central incisors, the detection of which may be accidental. Early diagnosis is essential since it allows timely extraction of the supernumerary tooth, preventing possible future alterations such as: the development of cysts, poor location of adjacent teeth, delayed eruption, interincisal diastema, apical resorption of neighboring teeth. Case report: The case presented is of a male pediatric patient, 6 years and 11 months old, who presented double mesiodens, whose finding was radiological, through a panoramic view, a requirement of the dentist for general dental control, in which could observe the presence of two supernumerary teeth, which were causing the rotation of the upper permanent incisors. The treatment was based on the early surgical extraction of the supernumerary teeth, to determine the approach it was necessary to carry out a tomographic study, once the extraction process was determined, and later the recovery of the patient, and radiographic and clinical follow-up, it was achieved. proper eruption of the permanent upper central incisors, to date periodic checks and placement of upper and lower expansion plates are performed. Conclusion: In this case, the treatment is early extraction, and due to timely diagnosis and optimal patient conditions such as: physiological root resorption of deciduous teeth, location of supernumerary teeth, as well as the Nolla stage of the teeth. upper central incisors, allows the chosen treatment to be optimal and with the least traumatic conditions possible


Assuntos
Humanos , Masculino , Criança , Radiografia Dentária
6.
Rev. colomb. neumol ; 34(2): 93-96, July-Dec. 2022.
Artigo em Espanhol | LILACS, COLNAL | ID: biblio-1412942

RESUMO

Desde la aparición de la enfermedad por SARS-CoV-2, han cambiado paradigmas en la ciencia médica y actualmente nos enfrentamos a las repercusiones a largo plazo que algunos de los pacientes desarrollan. Entre el grupo de pacientes que han cursado con neumonía severa-síndrome de dificultad respiratoria aguda (SDRA) por SARS-CoV-2 y que requirieron intubación orotraqueal (IOT), se documentan complicaciones multisistémicas (1-4). En este artículo destacaremos las complicaciones relacionadas con la vía aérea que se presentan en forma de estenosis benignas, siendo las lesiones subglóticas tipo simples o complejas las más frecuentes. A continuación, presentamos el caso de un paciente que presentó estenosis traqueales pos-IOT a causa de una neumonía severa por COVID-19 con diagnóstico, seguimiento y manejo por un grupo multidisciplinario de vía aérea.


Since the appearance of SARSCoV-2 disease, paradigms have changed in medical science, and we are currently facing the long-term repercussions that some of the patients develop. Within the group of patients who have had severe pneumonia - Acute respiratory distress syndrome (ARDS) due to SARSCoV-2 and who required orotracheal intubation (OTI), multisystemic complications are documented (1-4), in In this article, we will highlight airway-related complications that occur in the form of benign stenosis, with simple or complex subglottic lesions being the most common. We present a case of a patient who presented tracheal stenosis post-OTI due to severe COVID-19 pneumonia as main diagnosis, follow-up, and management by a multidisciplinary airway group.


Assuntos
Humanos , Pneumonia , Estenose Traqueal , Síndrome do Desconforto Respiratório do Recém-Nascido , SARS-CoV-2 , COVID-19 , Intubação
7.
Int J Mol Sci ; 23(18)2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36142275

RESUMO

Gain-of-function mutations of dynamin-2, a mechano-GTPase that remodels membrane and actin filaments, cause centronuclear myopathy (CNM), a congenital disease that mainly affects skeletal muscle tissue. Among these mutations, the variants p.A618T and p.S619L lead to a gain of function and cause a severe neonatal phenotype. By using total internal reflection fluorescence microscopy (TIRFM) in immortalized human myoblasts expressing the pH-sensitive fluorescent protein (pHluorin) fused to the insulin-responsive aminopeptidase IRAP as a reporter of the GLUT4 vesicle trafficking, we measured single pHluorin signals to investigate how p.A618T and p.S619L mutations influence exocytosis. We show here that both dynamin-2 mutations significantly reduced the number and durations of pHluorin signals induced by 10 µM ionomycin, indicating that in addition to impairing exocytosis, they also affect the fusion pore dynamics. These mutations also disrupt the formation of actin filaments, a process that reportedly favors exocytosis. This altered exocytosis might importantly disturb the plasmalemma expression of functional proteins such as the glucose transporter GLUT4 in skeletal muscle cells, impacting the physiology of the skeletal muscle tissue and contributing to the CNM disease.


Assuntos
Dinamina II , Miopatias Congênitas Estruturais , Dinamina II/genética , Dinamina II/metabolismo , Exocitose , Mutação com Ganho de Função , Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Humanos , Ionomicina , Músculo Esquelético/metabolismo , Mutação , Mioblastos/metabolismo , Miopatias Congênitas Estruturais/metabolismo
8.
PLoS One ; 17(1): e0261953, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35030178

RESUMO

During recent years, multimorbidity has taken relevance because of the impact of causes in the system, people, and their families, which has been a priority in the health care plan. Interventions strategies and their implementation are still an emerging topic. In this context, Centro de Innovación en Salud ANCORA UC, together with Servicio de Salud Metropolitano Sur Oriente, implemented as a pilot study High-Risk Multimorbidity Integrated Care strategy. This study aimed to evaluate the impact of this strategy in terms of health services utilization and mortality. A cohort study was conducted with high-risk patients with multimorbidity, stratified by ACG®, intervened between April 2017 and December 2019. The studied population was 3,933 patients who belonged to similar size and location primary care centers. The impact analysis was performed used generalized linear models. Results showed that intervened patients had a significantly lower incidence in mortality (OR 0.56; 95% CI 0.40-0.77), hospital admissions, length of stay, and the number of hospital emergency consultancies. With the proper barriers and facilitators of a real context intervention, the implementation process allowed the systematization and consolidation of the intervention provided in this study. The training for new roles and the constant implementation support from the Centro de Innovación en Salud ANCORA UC team were essential in the progress and success of the intervention. A complete description of the high-risk intervention strategy is provided to contribute to this emerging topic and facilitate its scale-up. We can conclude that this complex intervention was feasible to be implemented in a real context. The Ministry of Health has taken the systematization and consolidation of the conditions for the national scale-up.


Assuntos
Prestação Integrada de Cuidados de Saúde , Multimorbidade , Atenção Primária à Saúde , Saúde Pública , Idoso , Idoso de 80 Anos ou mais , Chile , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
9.
Rev. Méd. Clín. Condes ; 32(4): 400-413, jul - ago. 2021. tab, ilus, graf
Artigo em Espanhol | LILACS | ID: biblio-1518710

RESUMO

En Chile, el 70% de la población de 15 años y más vive con multimorbilidad, es decir, con la presencia de dos o más condiciones crónicas de forma simultánea. El abordaje clásico de la cronicidad por programas en atención primaria de salud, con foco en la enfermedad, se expresa en cuidados fragmentados, ineficaces y muy alejados de los principios de centralidad en la persona, integralidad y continuidad del cuidado impulsados desde el modelo de atención integral de salud familiar y comunitario (MAIS). La estrategia de cuidado integral centrado en las personas para la promoción, prevención y manejo de la cronicidad en contexto de multimorbilidad (ECICEP), se constituye en una respuesta a esta problemática.La multimorbilidad representa un desafío de gran envergadura en el rediseño desde una atención fragmentada hacia el cuidado integral centrado en la persona. Implica un proceso de gestión del cambio, en donde es necesario sensibilizar en la urgencia y sentido del cambio, estratificar a la población según riesgo, capacitar a los equipos de salud, reorganizar los procesos administrativos (agendamiento, registro clínico) y clínicos (ingreso y control integral, planes de cuidado consensuados, gestión del cuidado, seguimiento a distancia, automanejo), así como favorecer el liderazgo y acompañamiento del cambio y el trabajo colaborativo en red.Este proceso requiere voluntad política, con sentido de urgencia del cambio y gradualidad, para que su instalación sea eficiente y respetuosa. Por ello, se inicia el proceso con las personas de alta complejidad, que son quienes tienen más riesgo de hospitalizaciones evitables y otras complicaciones


In Chile, 70% of the population aged 15 years and over lives with multimorbidity, that is, with the presence of two or more chronic conditions simultaneously. The classic approach to chronicity by programs in primary health care, with a focus on the disease, is expressed in fragmented care, ineffective and far removed from the principles of person-centeredness, comprehensiveness and continuity of care promoted by the Comprehensive Family and Community Health Care Model (MAIS). The People-Centered Integrated Care Strategy for the Promotion, Prevention and Management of Chronicity in the Context of Multimorbidity (ECICEP) is a response to this problem. Chronic multimorbidity represents a major challenge in the redesign from fragmented care to comprehensive person-centered care. It implies a process of change management, in which it is necessary to raise awareness of the urgency and sense of change, stratify the population according to risk, train health teams, reorganize administrative (scheduling, clinical records) and clinical processes (admission and comprehensive control, consensual care plans, care management, remote follow-up, self-management), as well as promoting leadership and accompaniment of change, networking and intersectoral coordination. This process requires political will, with a sense of urgency of change and gradualness, so that its installation is efficient and respectful. For this reason, the process begins with highly complex patients, who are at the greatest risk of avoidable hospitalizations and other complications.


Assuntos
Humanos , Assistência Centrada no Paciente , Assistência Integral à Saúde , Multimorbidade , Atenção Primária à Saúde , Doença Crônica , Continuidade da Assistência ao Paciente , Autogestão , Gestão de Mudança
10.
Rev. colomb. reumatol ; 27(supl.2): 109-124, oct.-dic. 2020. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-1341346

RESUMO

RESUMEN El síndrome de Sjögren es una enfermedad autoinmunitaria sistémica con un alto impacto individual y social. El compromiso pulmonar presenta múltiples manifestaciones, con impacto en calidad de vida y riesgo de mortalidad. El abordaje dinámico integrado mediante un grupo de diagnóstico multidisciplinario que incluya expertos en neumología, reumatología, radiología y patología tiene el potencial de impactar en la identificación, las estrategias de manejo y los desenlaces. Aunque es necesario reconocer tempranamente a los pacientes con mayor riesgo, en la actualidad no se cuenta con biomarcadores confiables. Las estrategias de manejo farmacológico se basan en la inmunomodulación, pero la evidencia para su uso es de baja calidad. Promover el entrenamiento y la sensibilización del personal de salud podría reducir los retrasos en el acceso a una evaluación especializada.


ABSTRACT Sjögren's syndrome is a systemic autoimmune disease with a high burden for the individual, as well as society. Pulmonary compromise presents with a myriad of manifestations that influence patient quality of life and mortality risk. An integrated dynamic approach by a multidisciplinary diagnostic discussion team that includes experts in chest diseases, rheumatology, radiology, and pathology has the potential to improve the identification, management strategies, and outcomes. Although early recognition of patients at high risk is essential, there is currently a lack of reliable biomarkers. Pharmacological therapies are based on immunomodulation, although the evidence to support their use is of low quality. Increasing awareness and training among healthcare professionals may reduce a delayed access to specialized assessment.


Assuntos
Humanos , Síndrome de Sjogren , Pulmão , Qualidade de Vida , Mortalidade , Diagnóstico
11.
Tumour Biol ; 41(5): 1010428319851014, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31109257

RESUMO

Lung cancer has a high mortality rate in men and women worldwide. Approximately 15% of diagnosed patients with this type of cancer do not exceed the 5-year survival rate. Unfortunately, diagnosis is established in advanced stages, where other tissues or organs can be affected. In recent years, lineage-specific transcription factors have been associated with a variety of cancers. One such transcription factor possibly regulating cancer is RUNX2, the master gene of early and late osteogenesis. In thyroid and prostate cancer, it has been reported that RUNX2 regulates expression of genes important in tumor cell migration and invasion. In this study, we report on RUNX2/ p57 overexpression in 16 patients with primary non-small cell lung cancer and/or metastatic lung cancer associated with H3K27Ac at P1 gene promoter region. In some patients, H3K4Me3 enrichment was also detected, in addition to WDR5, MLL2, MLL4, and UTX enzyme recruitment, members of the COMPASS-LIKE complex. Moreover, transforming growth factor-ß induced RUNX2/ p57 overexpression and specific RUNX2 knockdown supported a role for RUNX2 in epithelial mesenchymal transition, which was demonstrated through loss of function assays in adenocarcinoma A549 lung cancer cell line. Furthermore, RUNX2 increased expression of epithelial mesenchymal transition genes VIMENTIN, TWIST1, and SNAIL1, which reflected increased migratory capacity in lung adenocarcinoma cells.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/secundário , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Epigênese Genética , Transição Epitelial-Mesenquimal , Neoplasias Pulmonares/patologia , Regiões Promotoras Genéticas , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Estudos de Casos e Controles , Movimento Celular , Proliferação de Células , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Células Tumorais Cultivadas
12.
Sci Rep ; 7(1): 4580, 2017 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-28676641

RESUMO

Dynamin-2 is a ubiquitously expressed GTP-ase that mediates membrane remodeling. Recent findings indicate that dynamin-2 also regulates actin dynamics. Mutations in dynamin-2 cause dominant centronuclear myopathy (CNM), a congenital myopathy characterized by progressive weakness and atrophy of skeletal muscles. However, the muscle-specific roles of dynamin-2 affected by these mutations remain elusive. Here we show that, in muscle cells, the GTP-ase activity of dynamin-2 is involved in de novo actin polymerization as well as in actin-mediated trafficking of the glucose transporter GLUT4. Expression of dynamin-2 constructs carrying CNM-linked mutations disrupted the formation of new actin filaments as well as the stimulus-induced translocation of GLUT4 to the plasma membrane. Similarly, mature muscle fibers isolated from heterozygous knock-in mice that harbor the dynamin-2 mutation p.R465W, an animal model of CNM, exhibited altered actin organization, reduced actin polymerization and impaired insulin-induced translocation of GLUT4 to the sarcolemma. Moreover, GLUT4 displayed aberrant perinuclear accumulation in biopsies from CNM patients carrying dynamin-2 mutations, further suggesting trafficking defects. These results suggest that dynamin-2 is a key regulator of actin dynamics and GLUT4 trafficking in muscle cells. Our findings also support a model in which impairment of actin-dependent trafficking contributes to the pathological mechanism in dynamin-2-associated CNM.


Assuntos
Actinas/metabolismo , Dinamina II/genética , Predisposição Genética para Doença , Células Musculares/metabolismo , Mutação , Miopatias Congênitas Estruturais/genética , Miopatias Congênitas Estruturais/metabolismo , Actinas/química , Animais , Modelos Animais de Doenças , Dinamina II/metabolismo , Ativação Enzimática , Expressão Gênica , Estudos de Associação Genética , Transportador de Glucose Tipo 4/metabolismo , Humanos , Camundongos , Mioblastos/metabolismo , Miopatias Congênitas Estruturais/patologia , Ligação Proteica , Multimerização Proteica , Transporte Proteico
13.
Univ. psychol ; 15(4): 1-14, oct.-dic. 2016. graf, tab
Artigo em Espanhol | LILACS | ID: biblio-963197

RESUMO

Antecedentes: El objetivo de esta investigación fue la adaptación al castellano de la Escala HPLP-II de Walker y Hill-Polerecky en población trabajadora, teniendo en cuenta que los estilos de vida tienen una gran influencia en la salud laboral. Los seis factores que mide la escala original son: Actividad física, Crecimiento espiritual, Manejo del estrés, Nutrición, Relaciones interpersonales y Responsabilidad hacia la salud. Método: participaron en el estudio 513 trabajadores (48.1 % hombres, 51.9 % mujeres), escogidos mediante un muestreo no probabilístico. Se utilizaron los programas FACTOR (versión 7.2) y SPSS 20.0. Resultados: En la escala HPLP-II, los resultados apoyan una solución de cuatro factores, reduciéndose el número de ítems de 52 a 48, con una fiabilidad adecuada (Responsabilidad hacia la salud = 0.81, Actividad física = 0.86, Nutrición = 0.7 y Crecimiento espiritual y relaciones interpersonales = 0.88) e indicios de validez en relación con MBI-GS, Autoeficacia, Satisfacción con la Vida y Engagement. Conclusiones: Las Escala HPLP-II constituyen un instrumento fiable y válido, adecuado para ser usado en español.


Background: The lifestyles have great influence on the occupational health of workers. The objective of this research is the Spanish adaptation of HPLP-II Scale Walker and Hill-Polerecky in working population. Factors that measures the original scale are 6 and correspond to physical activity, Spiritual Growth, Stress Management, Nutrition, Interpersonal Relations and Responsibility to health. Method: Participants were 513 workers (48.1% male, 51.9% female), obtained by a non-probability sampling. We used the FACTOR programs (version 7.2) and SPSS 20.0. Results: In the HPLP-II scale, the results support a four-factor solution reducing the number of items 52-48, presenting adequate reliability (Responsibility towards health = 0.81, = 0.86 Physical Activity, Nutrition = 0.7 and spiritual growth and interpersonal relations = 0.88) and evidence of validity: MBI-GS, Self-Efficacy, Life Satisfaction and Engagement. Conclusions: HPLP-II Scale is a reliable and valid, suitable for use in Spanish instrument.

14.
J Community Health ; 39(3): 409-15, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24276617

RESUMO

Peru struggles to prevent cervical cancer (CC). In the jungle, prevention programs suffer from significant barriers although technology exists to detect CC precursors. This study used community based participatory research (CBPR) methods to overcome barriers. The objective was to evaluate the utility of CBPR techniques in a mother-child screen/treat and vaccinate program for CC prevention in the Peruvian jungle. The CC prevention program used self-sampling for human papillomavirus (HPV) for screening, cryotherapy for treatment and the HPV vaccine Gardasil for vaccination. Community health leaders (HL) from around Iquitos participated in a two half day educational course. The HLs then decided how to implement interventions in their villages or urban sectors. The success of the program was measured by: (1) ability of the HLs to determine an implementation plan, (2) proper use of research forms, (3) participation and retention rates, and (4) participants' satisfaction. HLs successfully registered 320 women at soup kitchens, schools, and health posts. Screening, treatment, and vaccination were successfully carried out using forms for registration, consent, and results with minimum error. In the screen/treat intervention 100% of participants gave an HPV sample and 99.7% reported high satisfaction; 81% of HPV + women were treated, and 57% returned for 6-month followup. Vaccine intervention: 98% of girls received the 1st vaccine, 88% of those received the 2nd, and 65% the 3rd. CBPR techniques successfully helped implement a screen/treat and vaccinate CC prevention program around Iquitos, Peru. These techniques may be appropriate for large-scale preventive health-care interventions.


Assuntos
Promoção da Saúde/organização & administração , Programas de Rastreamento , Núcleo Familiar , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus , Neoplasias do Colo do Útero/prevenção & controle , Adolescente , Adulto , Criança , Pesquisa Participativa Baseada na Comunidade , Detecção Precoce de Câncer , Feminino , Humanos , Pessoa de Meia-Idade , Mães , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/terapia , Aceitação pelo Paciente de Cuidados de Saúde , Peru , População Rural , Vacinação
15.
Rev Esp Salud Publica ; 87(4): 393-406, 2013.
Artigo em Espanhol | MEDLINE | ID: mdl-24100777

RESUMO

BACKGROUND: Current communication technologies can be used in health education. The aim was to assess the process of an online program designed to prevent cancer risk behaviours using an educational website and mobile phones. METHODS: High school students from Spain and Mexico were recruited during 3 academic years (2009-12) to participate in a web-based program supplemented with mobile phone messages (SMS) which aim was to prevent cancer risk behaviours. The program was designed as a randomized trial, with control and experimental group (EG). Recruitment and adherence were analyzed using data of the Web management platform and Google Analytics. RESULTS: 3,855 students started the logging on the program of which 2,001 (51.9%) completed the questionnaire.77.5% were Mexicans, 13 years old (40.6%), with good academic level (68.7%) and with parents (49.6%) and mothers (53.9%) having university degree. 56.4% recorded a phone number to receive SMS. The EG consisted of 1,014 students and the averages of their visits to the website were 31.6 in the first year, 21.8 in the second and 21.9 in the third. Each adolescent of the EG was able to incorporate 1.16 adults (total 1,172) and other 1,076 were recorded spontaneously. Retention rate at the end of follow-up was 41.5% and was higher among those who were best students (OR: 12,5), Mexicans (OR: 4.4), 12 years old (OR: 3.1) and have been incorporated in the first three months of the implementation (OR: 2.8). CONCLUSION: Students' recruitment and retention was scarce, mainly in Spain. However students involved visited the program website with sufficient amount of time to achieve good results.


Assuntos
Telefone Celular , Comportamentos Relacionados com a Saúde , Educação em Saúde/métodos , Internet , Neoplasias/prevenção & controle , Estudantes , Adolescente , Adulto , Telefone Celular/estatística & dados numéricos , Criança , Atenção à Saúde , Feminino , Humanos , Internet/estatística & dados numéricos , Masculino , México , Pais , Avaliação de Programas e Projetos de Saúde , Projetos de Pesquisa , Espanha , Inquéritos e Questionários , Universidades
16.
Physiol Biochem Zool ; 84(3): 333-40, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21527824

RESUMO

Hummingbirds (family Trochilidae) represent an extreme outcome in vertebrate physiological design and are the only birds capable of sustained hovering. The giant hummingbird (Patagona gigas) is the largest trochilid, with a mass of ~20 g, and is found over an altitudinal range from 0 to 4,500 m above sea level. We report here measurements of daily, basal, and hovering rates of oxygen consumption in the giant hummingbird; compare these values with data from smaller hummingbirds; and assess overall metabolic and allometric limits to trochilid body size. The sustained metabolic scope (i.e., the ratio of daily energy expenditure to basal metabolic rate) in the giant hummingbird is higher than that in smaller hummingbirds but lies below a proposed theoretical maximum value for endotherms. Scaling exponents in the allometric relationships for different modes of energetic expenditure were comparable, suggesting that the giant hummingbird, although a clear outlier in terms of body size, does not obviously deviate from metabolic relationships derived from other trochilid taxa.


Assuntos
Aves/fisiologia , Metabolismo Energético , Animais , Metabolismo Basal , Tamanho Corporal , Chile , Voo Animal , Consumo de Oxigênio
17.
Arch. latinoam. nutr ; Arch. latinoam. nutr;58(3): 280-285, sept. 2008. graf, tab
Artigo em Espanhol | LILACS | ID: lil-588731

RESUMO

Se ha descrito una importante actividad física en pacientes con trastornos alimentarios y la hiperactividad llega a estar presente en más del 80 por ciento en las fases graves. El inicio de la restricción alimentaria se produce a edades más tempranas cuando existe ejercicio físico intenso, la insatisfacción corporal es mayor entre pacientes practicantes de ejercicio y la presencia de actividad intensa en la anorexia precede a la dieta restrictiva. El objetivo de nuestro estudio fue evaluar la presencia de ejercicio al inicio del trastorno, y las posibles diferencias en la modalidad, según edad, sexo y subgrupos diagnósticos. La evaluación del ejercicio de los pacientes (N = 745), se hizo a través de la entrevista Eating Disorders Examination (EDE). Se recogió la presencia o no de actividad física conducente al consumo calórico, la pérdida de peso o la modificación de la figura, tipo de actividad e intensidad. Se consideró sólo la presencia de intensidad moderada o alta, y con clara relación con los objetivos mencionados. 407 pacientes (54,63 por ciento) realizaban ejercicio:68,96 por ciento en anorexia, 68,96 por ciento en bulimia y 34,73 por ciento en los trastornos no especificados, sin diferencias significativas entre hombres y mujeres. La hiperactividad fue lo más frecuente, (47,42 por ciento), seguida de la actividad en gimnasio (25,79 por ciento). Considerando los diferentes diagnósticos observamos diferencias significativas. La correcta evaluación del ejercicio excesivo es fundamental en los trastornos alimentarios a fin de incluir dicho aspecto en los programas de tratamiento.


Intense physical activity has been reported in patients with eating disorders, and hyperactivity can be found in more than 80 percent in severe stages. The beginning of food restriction occurs at earlier ages if there is an intense physical activity; body dissatisfaction is more intense among patients who practice exercise; and the presence of intense activity in anorexia nervosa usually precedes to the restrictive diet. The aim of this study was to evaluate the presence of exercise at the beginning of the eating disorder, and to analyze possible differences in the kind of exercise, according to age, sex and diagnostic subgroups. In order to evaluate the exercise 745 patients were assessed by the Eating Disorders Examination (EDE). The presence of physical activity (driving to caloric consumption, weight loss or modification of body shape), kind of activity, and its intensity were considered. Only the presence of moderate or high intensity clearly related with the mentioned objectives was considered. 407 patients (54,63 percent) engaged in exercise: 68,96 percent with anorexia, 68,96 percent with bulimia, and 34,73 percent with other non-specified eating disorders. There were not significant differences between men and women. Hyperactivity was the most frequent (47,42 percent), followed by gym activity (25,79 percent). Taking into account the different clinic subgroups, we could observe significant differences. To assess eating disorders, a correct evaluation of the physical activity should be necessary in order to include this aspect in treatment programs.


Assuntos
Humanos , Masculino , Feminino , Anorexia/patologia , Bulimia/patologia , Exercício Físico , Transtornos da Alimentação e da Ingestão de Alimentos/patologia , Comportamento Alimentar , Ciências da Nutrição
18.
Artigo em Inglês | MEDLINE | ID: mdl-18584181

RESUMO

We studied the photopic spectral sensitivity in the green-backed firecrown, Sephanoides sephaniodes, a South American hummingbird, and its possible ecological relationship with preferred flowers and body colouration. Avian colour vision is in general tetrachromatic with at least four types of cones, which vary in sensitivity from the near ultraviolet (UV) to the red wavelength range. Hummingbirds represent an important family of birds, yet little is known about their eye sensitivity, especially about the role of photoreceptors and their oil droplet complements. The photopic electroretinogram shows a main sensitivity peak at 560 nm and a secondary peak in the UV, and may be explained by the presence of four single cones (lambda max at approximately 370, 440, 508 and 560 nm), and a double cone (lambda max at 560 nm) screened by oil droplets. The flowers preferred by the firecrown are those in which the red-green wavelength region predominates and have higher contrast than other flowers. The crown plumage of males is highly iridescent in the red wavelength range (peak at 650 nm) and UV; when plotted in a high-dimensional tetrachromatic space, it falls in a "red + UV" purple hue line, suggesting a potential significant communication signal for sexual differentiation.


Assuntos
Aves/fisiologia , Visão de Cores/fisiologia , Transdução de Sinal Luminoso/fisiologia , Células Fotorreceptoras de Vertebrados/fisiologia , Retina/fisiologia , Animais , Aves/anatomia & histologia , Cor , Visão de Cores/efeitos da radiação , Eletrorretinografia , Plumas/fisiologia , Comportamento Alimentar/fisiologia , Comportamento Alimentar/efeitos da radiação , Feminino , Flores/fisiologia , Luz , Transdução de Sinal Luminoso/efeitos da radiação , Masculino , Potenciais da Membrana/fisiologia , Óleos/metabolismo , Estimulação Luminosa , Células Fotorreceptoras de Vertebrados/citologia , Células Fotorreceptoras de Vertebrados/efeitos da radiação , Pigmentação/fisiologia , Retina/citologia , Retina/efeitos da radiação , Comportamento Sexual Animal/fisiologia , Especificidade da Espécie , Raios Ultravioleta
19.
Arch Latinoam Nutr ; 58(3): 280-5, 2008 Sep.
Artigo em Espanhol | MEDLINE | ID: mdl-19137991

RESUMO

Intense physical activity has been reported in patients with eating disorders, and hyperactivity can be found in more than 80% in severe stages. The beginning of food restriction occurs at earlier ages if there is an intense physical activity; body dissatisfaction is more intense among patients who practice exercise; and the presence of intense activity in anorexia nervosa usually precedes to the restrictive diet. The aim of this study was to evaluate the presence of exercise at the beginning of the eating disorder, and to analyze possible differences in the kind of exercise, according to age, sex and diagnostic subgroups. In order to evaluate the exercise 745 patients were assessed by the Eating Disorders Examination (EDE). The presence of physical activity (driving to caloric consumption, weight loss or modification of body shape), kind of activity, and its intensity were considered. Only the presence of moderate or high intensity clearly related with the mentioned objectives was considered. 407 patients (54.63%) engaged in exercise: 68.96% with anorexia, 68.96% with bulimia, and 34.73% with other non-specified eating disorders. There were not significant differences between men and women. Hyperactivity was the most frequent (47.42%), followed by gym activity (25.79%). Taking into account the different clinic subgroups, we could observe significant differences. To assess eating disorders, a correct evaluation of the physical activity should be necessary in order to include this aspect in treatment programs.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Exercício Físico/psicologia , Comportamento Alimentar/psicologia , Transtornos da Alimentação e da Ingestão de Alimentos/psicologia , Adolescente , Adulto , Distribuição por Idade , Anorexia Nervosa/etiologia , Anorexia Nervosa/fisiopatologia , Transtorno do Deficit de Atenção com Hiperatividade/complicações , Bulimia/etiologia , Bulimia/psicologia , Exercício Físico/fisiologia , Comportamento Alimentar/fisiologia , Transtornos da Alimentação e da Ingestão de Alimentos/etiologia , Feminino , Humanos , Masculino , Atividade Motora/fisiologia , Fatores Sexuais , Adulto Jovem
20.
Guatemala; INCAP; 2006. 140 p. ilus, tab. (MDE-156).
Monografia em Espanhol | LILACS, LIGCSA, REPincaP | ID: biblio-1398169

RESUMO

El manual presenta, el producto del trabajo cuidadoso y fundamentado de la Dra. Frances Thompson y colaboradores, constituye una fuente de información objetiva sobre métodos de evaluación dietética, que será de interés para nutriólogos, médicos, salubristas y otros interesados en el tema. El Instituto de Nutrición de Centro América y Panamá (INCAP), pone a disposición de estudiosos de la nutrición, la salud clínica y pública, y de otros campos vinculados a la Seguridad Alimentaria y Nutricional, esta valiosa publicación, en su versión en español, que con seguridad servirá también al desarrollo de nuevos métodos y técnicas dietéticas


Assuntos
Avaliação Nutricional , Saúde , Dietética , Estudos de Avaliação como Assunto , Abastecimento de Alimentos , Métodos
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