RESUMO
Mitochondrial dysfunction is a significant factor in the development of Alzheimer's disease (AD). Previous studies have demonstrated that the expression of tau cleaved at Asp421 by caspase-3 leads to mitochondrial abnormalities and bioenergetic impairment. However, the underlying mechanism behind these alterations and their impact on neuronal function remains unknown. To investigate the mechanism behind mitochondrial dysfunction caused by this tau form, we used transient transfection and pharmacological approaches in immortalized cortical neurons and mouse primary hippocampal neurons. We assessed mitochondrial morphology and bioenergetics function after expression of full-length tau and caspase-3-cleaved tau. We also evaluated the mitochondrial permeability transition pore (mPTP) opening and its conformation as a possible mechanism to explain mitochondrial impairment induced by caspase-3 cleaved tau. Our studies showed that pharmacological inhibition of mPTP by cyclosporine A (CsA) prevented all mitochondrial length and bioenergetics abnormalities in neuronal cells expressing caspase-3 cleaved tau. Neuronal cells expressing caspase-3-cleaved tau showed sustained mPTP opening which is mostly dependent on cyclophilin D (CypD) protein expression. Moreover, the impairment of mitochondrial length and bioenergetics induced by caspase-3-cleaved tau were prevented in hippocampal neurons obtained from CypD knock-out mice. Interestingly, previous studies using these mice showed a prevention of mPTP opening and a reduction of mitochondrial failure and neurodegeneration induced by AD. Therefore, our findings showed that caspase-3-cleaved tau negatively impacts mitochondrial bioenergetics through mPTP activation, highlighting the importance of this channel and its regulatory protein, CypD, in the neuronal damage induced by tau pathology in AD.
Assuntos
Doença de Alzheimer , Poro de Transição de Permeabilidade Mitocondrial , Animais , Camundongos , Doença de Alzheimer/metabolismo , Caspase 3/genética , Caspase 3/metabolismo , Peptidil-Prolil Isomerase F/metabolismo , Mitocôndrias/metabolismo , Poro de Transição de Permeabilidade Mitocondrial/metabolismoRESUMO
OBJECTIVE: This study aimed to characterize hand hygiene behavioural intention by hospital services clusters in a medium-sized hospital in an Ecuadorian city. METHODS: This is a cross-sectional study based on the World Health Organization Hand Hygiene Knowledge Questionnaire for Health-Care Workers. The responses on hand hygiene behavioural intention for the Five Moments for hand hygiene according to the World Health Organization were recorded in three categories: before patient contact, before and after sterile technique and management of body fluids, and after contact with the environment of the patient. The variables were the knowledge regarding the source of germs causing nosocomial infections, the optimal time to achieve disinfection with alcohol, hospital services clusters (clinical medicine, surgery, and therapeutic services), and history of previous formal hand hygiene training. The variables in each moment were analysed using a saturated log-linear model. RESULTS: The average age of participants was 34 years (Q1 32.1-Q3 36.4). Of them, 62% belonged to the clinic cluster and 87.6% had previous formal hand hygiene training. The incorrect response rates for before and after sterile technique and management of body fluids, before patient contact, and after contact with the environment of the patient were 30.2, 88.4, and 99.2%, respectively. In before patient contact, the incorrect responses for optimal time depended on the department (worse surgery cluster situation), and in before and after sterile technique and management of body fluids and after contact with the environment of the patient, the incorrect responses for source of germs depended on the previous formal hand hygiene training and the department (worse surgery and clinic clusters). CONCLUSION: The incorrect answer related to hand hygiene behavioural intention was high compared to other reports, and the worse situation was found in after contact with the environment of the patient and before patient contact. These data suggest the need of strengthening permanently the hand hygiene programme.
Assuntos
Infecção Hospitalar , Higiene das Mãos , Adulto , Estudos Transversais , Equador , Fidelidade a Diretrizes , Desinfecção das Mãos/métodos , Pessoal de Saúde/educação , Hospitais , Humanos , IntençãoRESUMO
SUMMARY OBJECTIVE: This study aimed to characterize hand hygiene behavioural intention by hospital services clusters in a medium-sized hospital in an Ecuadorian city. METHODS: This is a cross-sectional study based on the World Health Organization Hand Hygiene Knowledge Questionnaire for Health-Care Workers. The responses on hand hygiene behavioural intention for the Five Moments for hand hygiene according to the World Health Organization were recorded in three categories: before patient contact, before and after sterile technique and management of body fluids, and after contact with the environment of the patient. The variables were the knowledge regarding the source of germs causing nosocomial infections, the optimal time to achieve disinfection with alcohol, hospital services clusters (clinical medicine, surgery, and therapeutic services), and history of previous formal hand hygiene training. The variables in each moment were analysed using a saturated log-linear model. RESULTS: The average age of participants was 34 years (Q1 32.1-Q3 36.4). Of them, 62% belonged to the clinic cluster and 87.6% had previous formal hand hygiene training. The incorrect response rates for before and after sterile technique and management of body fluids, before patient contact, and after contact with the environment of the patient were 30.2, 88.4, and 99.2%, respectively. In before patient contact, the incorrect responses for optimal time depended on the department (worse surgery cluster situation), and in before and after sterile technique and management of body fluids and after contact with the environment of the patient, the incorrect responses for source of germs depended on the previous formal hand hygiene training and the department (worse surgery and clinic clusters). CONCLUSION: The incorrect answer related to hand hygiene behavioural intention was high compared to other reports, and the worse situation was found in after contact with the environment of the patient and before patient contact. These data suggest the need of strengthening permanently the hand hygiene programme.
RESUMO
Resumen El objetivo es conocer acerca del efecto indirecto de la inteligencia emocional en la autoeficacia académica a través del compromiso académico en una muestra de estudiantes universitarios del Ecuador. Para ello se realizó un análisis de tipo descriptivo correlacional, de determinación, de mediación parcial a través de SEM y de corte transversal. El instrumental empleado corresponde a la Brief Emotional Intelligence Inventory for Senior Citizens, la Utrecht Work Engagement Scale y la Escala de Autoeficacia Percibida Específica de Situaciones Académicas. La muestra estuvo conformada por 500 estudiantes (57.5 % mujeres y 42.4 % hombres), entre 18 y 45 años (M = 24.5 años; SD = 6.9), procedentes de dos universidades de Ambato y Quito en Ecuador y de 11 carreras de pregrado. Entre los resultados se encontró que los niveles de las variables en análisis son normales entre los estudiantes, aunque un 30 % se encuentran en zona de riesgo por baja autoeficacia académica. Se confirma la relación entre inteligencia emocional (r = .522; p < .01) y el compromiso académico (r = .326; p < .01) en la autoeficacia académica. Estas variables forman un modelo explicativo del 30.6 % del cambio de la varianza de la autoeficacia académica. Además, la inteligencia emocional ejerce un efecto indirecto sobre la autoeficacia académica por medio del compromiso académico (ab = .031; p < .01). Como conclusión se establece que la inteligencia emocional y el compromiso académico son predictores de la autoeficacia académica. Además, que el compromiso académico es una variable de mediación parcial entre la inteligencia emocional y la autoeficacia académica en universitarios del Ecuador. La inteligencia emocional tiene como propiedad que ejerce un efecto directo en la autoeficacia académica e indirecto-parcial por medio del compromiso.
Abstract The intrapersonal and self-influence elements of individuals are necessary to know the impact they maintain in the educational context, because they are strong internal motivators that direct the behaviour of the individual to carry out various activities, as well as their achievement and success. There is evidence of the capacities that students have to monitor, control and regulate their own behaviours in the learning process. Although historically academic performance has been associated with intelligence in general, elements such as self-monitoring, self-control, self-regulation, self-motivation and others are key pieces to prevent school failure and maintain an adequate school performance. Within educational research, phenomena such as emotional intelligence, engagement and academic self-efficacy stand out due to their impact on academic performance. There are several studies that analyse the existing dynamics of these three variables, although separately, so a multifactorial study could expand the current conception of these internal elements and their effect on education. This investigation's objectives are to identify the current state of emotional intelligence, engagement and academic self-efficacy in a sample of university students from Ecuador, as well as the relationship between these variables and the indirect effect of emotional intelligence on academic self-efficacy through academic engagement. Thus, this study is a descriptive correlational, determination and partial mediation analysis, carried out through SEM using the Brief Emotional Intelligence Inventory for Senior Citizens, the Utrecht Work Engagement Scale and the Scale of Perceived Self-efficacy Specific to Academic Situations. The sample was made up of 500 students (57.5 % women and 42.4 % men), between 18 and 45 years old (M = 24.5 years; SD = 6.9), from two universities in Ambato and Quito in Ecuador and 11 undergraduate majors. The participants were selected through an intentional non-probabilistic sampling with inclusion criteria, which were: (a) be legally enrolled in one of the universities in this study; (b) voluntary participation in the study; (c) signed participation consent; and (c) be of legal age. In general, the levels of emotional intelligence, engagement and self-efficacy are normal among students; however, in academic engagement, 30 % are in a risk zone. The relationship between emotional intelligence (r = 0.522; p < .01) and academic engagement (r = 0.326; p < .01) in academic self-efficacy is confirmed. Together, these variables form an explanatory model that can predict changes in variance by 30.6 %. The theoretical model proposed by means of structural linear regression has an adequate adjustment indicator χ. = 252.9; p < .001; df = 116; χ./df = 2.1; CFI = .96; TLI = .95; RMSEA = .049 [.040 - .057]; SRMR = .042. In addition, emotional intelligence has an indirect effect on academic self-efficacy through academic engagement (ab = .0031; p < .01). Among the conclusions of the study, it is mentioned that emotional intelligence and academic engagement are predictors of academic self-efficacy. Therefore, their interest and management in the educational context is relevant. Moreover, the academic engagement is a partial mediation variable between emotional intelligence and academic self-efficacy in university students in Ecuador. Emotional intelligence has the ability to exert not only direct effects, but also partial indirect effects through a third variable. One of the implications of the study is that the use of more contemporary methods such as SEM allows a broader vision of the modelling of academic behaviour, which is an important contribution because it significantly reduces measurement bias. In addition, these results contribute to the future development of psychoeducational intervention processes that contribute to the improvement of the academic performance of students and to the teaching-learning processes in general. Finally, it is important to replicate similar studies in order to generalize these findings.
RESUMO
Mitochondria are highly specialized organelles essential for the synapse, and their impairment contributes to the neurodegeneration in Alzheimer's disease (AD). Previously, we studied the role of caspase-3-cleaved tau in mitochondrial dysfunction in AD. In neurons, the presence of this AD-relevant tau form induced mitochondrial fragmentation with a concomitant reduction in the expression of Opa1, a mitochondrial fission regulator. More importantly, we showed that caspase-cleaved tau affects mitochondrial transport, decreasing the number of moving mitochondria in the neuronal processes without affecting their velocity rate. However, the molecular mechanisms involved in these events are unknown. We studied the possible role of motor proteins (kinesin 1 and dynein) and mitochondrial protein adaptors (RhoT1/T2, syntaphilin, and TRAK2) in the mitochondrial transport failure induced by caspase-cleaved tau. We expressed green fluorescent protein (GFP), GFP-full-length, and GPF-caspase-3-cleaved tau proteins in rat hippocampal neurons and immortalized cortical neurons (CN 1.4) and analyzed the expression and localization of these proteins involved in mitochondrial transport regulation. We observed that hippocampal neurons expressing caspase-cleaved tau showed a significant accumulation of a mitochondrial population in the soma. These changes were accompanied by evident mitochondrial bioenergetic deficits, including depolarization, oxidative stress, and a significant reduction in ATP production. More critically, caspase-cleaved tau significantly decreased the expression of TRAK2 in immortalized and primary hippocampal neurons without affecting RhoT1/T2 and syntaphilin levels. Also, when we analyzed the expression of motor proteins-Kinesin 1 (KIF5) and Dynein-we did not detect changes in their expression, localization, and binding to the mitochondria. Interestingly, the expression of truncated tau significantly increases the association of TRAK2 with mitochondria compared with neuronal cells expressing full-length tau. Altogether these results indicate that caspase-cleaved tau may affect mitochondrial transport through the increase of TRAK2-mitochondria binding and reduction of ATP production available for the process of movement of these organelles. These observations are novel and represent a set of exciting findings whereby tau pathology could affect mitochondrial distribution in neurons, an event that may contribute to synaptic failure observed in AD.
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Excessive alcohol intake affects hippocampal function and neuronal communication through oxidative stress and mitochondrial impairment. Previous studies have suggested that the melanocortin system (MCS) plays an essential role in alcohol consumption and addiction. The MCS is a hypothalamic region involved in regulating inflammatory processes in the brain, and its pharmacological activation through the melanocortin-4 receptor (MC4R) reduces both alcohol consumption and the neuroinflammatory responses in the brain. However, the cellular mechanisms involved in the beneficial actions of MCS against ethanol toxicity are not entirely understood. The objective of this study was to investigate the protective role of the MC4R pharmacological activator RO27-3225 on oxidative damage and mitochondrial impairment present in hippocampal neuronal cultures acutely exposed to ethanol (50, 75 mM, 24 h). Pre-treatment with RO27-3225 (250 nM, 1 h) prevented reactive oxygen species (ROS) increase, dysregulation of cytosolic calcium homeostasis, and mitochondrial potential loss induced by ethanol. Improvement of mitochondrial failure produced by RO27-3225 was accompanied by a significant increase in ATP production in ethanol-treated neurons. More importantly, RO27-3225 promoted the activation of the antioxidant pathway Nrf-2, demonstrated by an increase in the expression and nuclear translocation of Nrf-2, and upregulation of mRNA levels of NAD(P)H quinone oxidoreductase 1 (NQO1), an antioxidant enzyme which expression is activated by this pathway. These results suggest that the stimulation of MC4R prevents oxidative damage and mitochondrial stress induced by ethanol through the activation of the Nrf-2 pathway in cultured hippocampal neurons. These results are novel and demonstrate the critical function of MC4R in promoting antioxidant defense and reducing mitochondrial damage produced by ethanol in the brain.
Assuntos
Cálcio/metabolismo , Potencial da Membrana Mitocondrial/fisiologia , Mitocôndrias/metabolismo , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/fisiologia , Peptídeos/farmacologia , Receptor Tipo 4 de Melanocortina/metabolismo , Animais , Antioxidantes , Células Cultivadas , Depressores do Sistema Nervoso Central/toxicidade , Etanol/toxicidade , Hipocampo/citologia , Inflamação/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , NAD(P)H Desidrogenase (Quinona)/efeitos dos fármacos , NAD(P)H Desidrogenase (Quinona)/genética , Fator 2 Relacionado a NF-E2/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Neurônios/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Receptor Tipo 4 de Melanocortina/agonistasRESUMO
Acute ethanol treatment induces neurodegeneration in cultured neurons and can lead to brain damage in animal models. Neuronal cells exposed to ethanol showed an increase in reactive oxygen species (ROS), oxidative damage and mitochondrial impairment contributing to synaptic failure. However, the underlying mechanisms of these events are not well understood. Here, we studied the contribution of NADPH oxidase, as a relevant source of ROS production in the brain, to mitochondrial impairment and oxidative stress induced by ethanol. We used primary hippocampal neurons subjected to an acute treatment of ethanol at increasing concentrations (25, 50, and 75 mM, 24 h), and we evaluated ROS production, mitochondrial function, and synaptic vesicle activity. Our studies showed that after ethanol administration, hippocampal neurons presented an increase in ROS levels, mitochondrial dysfunction, calcium handling defects, and synaptic impairment. Interestingly, treatment with the NADPH inhibitor, apocynin, significantly prevented oxidative stress, mitochondrial dysfunction, and the impairment of synaptic vesicle activity induced by ethanol treatment. These results indicate that NADPH oxidase could be a key participant in the molecular mechanism by which alcohol affects the brain.
Assuntos
Intoxicação Alcoólica/enzimologia , Intoxicação Alcoólica/patologia , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Mitocôndrias/efeitos dos fármacos , NADPH Oxidases , Neurônios/efeitos dos fármacos , Neurônios/patologia , Estresse Oxidativo , Trifosfato de Adenosina/metabolismo , Animais , Sinalização do Cálcio/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Mitocôndrias/metabolismo , Mitocôndrias/ultraestrutura , Gravidez , Cultura Primária de Células , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio , Sinapses/efeitos dos fármacos , Vesículas Sinápticas/efeitos dos fármacosRESUMO
BACKGROUND: The internet has become an important source of health information for users worldwide. The novel coronavirus caused a pandemic search for information with broad dissemination of false or misleading health information. OBJECTIVE: The aim of this study was to evaluate the quality and readability of online information about the coronavirus disease (COVID-19), which was a trending topic on the internet, using validated instruments and relating the quality of information to its readability. METHODS: The search was based on the term "Wuhan Coronavirus" on the Google website (February 6, 2020). At the search time, the terms "COVID-19" or "SARS-CoV-2" (severe acute respiratory syndrome coronavirus 2) did not exist. Critical analysis was performed on the first 110 hits using the Health on the Net Foundation Code of Conduct (HONcode), the Journal of the American Medical Association (JAMA) benchmark, the DISCERN instrument, and Google ranking. RESULTS: The first 110 websites were critically analyzed, and only 1.8% (n=2) of the websites had the HONcode seal. The JAMA benchmark showed that 39.1% (n=43) of the websites did not have any of the categories required by this tool, and only 10.0% (11/110) of the websites had the four quality criteria required by JAMA. The DISCERN score showed that 70.0% (n=77) of the websites were evaluated as having a low score and none were rated as having a high score. CONCLUSIONS: Nonhealth personnel and the scientific community need to be aware about the quality of the information they read and produce, respectively. The Wuhan coronavirus health crisis misinformation was produced by the media, and the misinformation was obtained by users from the internet. The use of the internet has a risk to public health, and, in cases like this, the governments should be developing strategies to regulate health information on the internet without censuring the population. By February 6, 2020, no quality information was available on the internet about COVID-19.
Assuntos
Comunicação , Compreensão , Informação de Saúde ao Consumidor , Infecções por Coronavirus/prevenção & controle , Coronavirus , Internet , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Betacoronavirus , COVID-19 , Informação de Saúde ao Consumidor/normas , Humanos , Disseminação de Informação , Serviços de Informação , Leitura , SARS-CoV-2RESUMO
Many studies have reported that alcohol produces harmful effects on several brain structures, including the hippocampus, in both rodents and humans. The hippocampus is one of the most studied areas of the brain due to its function in learning and memory, and a lot of evidence suggests that hippocampal failure is responsible for the cognitive loss present in individuals with recurrent alcohol consumption. Mitochondria are organelles that generate the energy needed for the brain to maintain neuronal communication, and their functional failure is considered a mediator of the synaptic dysfunction induced by alcohol. In this review, we discuss the mechanisms of how alcohol exposure affects neuronal communication through the impairment of glutamate receptor (NMDAR) activity, neuroinflammatory events and oxidative damage observed after alcohol exposure, all processes under the umbrella of mitochondrial function. Finally, we discuss the direct role of mitochondrial dysfunction mediating cognitive and memory decline produced by alcohol exposure and their consequences associated with neurodegeneration.
Assuntos
Etanol/efeitos adversos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Mitocôndrias/efeitos dos fármacos , Receptores de N-Metil-D-Aspartato/metabolismo , Transmissão Sináptica/efeitos dos fármacos , Animais , HumanosRESUMO
In the last few decades, many reports have suggested that mitochondrial function impairment is a hallmark of Alzheimer's disease (AD). Although AD is a neurodegenerative disorder, mitochondrial damage is also present in patients' peripheral tissues, suggesting a target to develop new biomarkers. Our previous findings indicate that AD fibroblasts show specific defects in mitochondrial dynamics and bioenergetics, which affects the generation of adenosine triphosphate (ATP). Therefore, we explored the possible mechanisms involved in this mitochondrial failure. We found that compared with normal fibroblasts, AD fibroblasts had mitochondrial calcium dysregulation. Further, AD fibroblasts showed a persistent activation of the non-specific mitochondrial calcium channel, the mitochondrial permeability transition pore (mPTP). Moreover, the pharmacological blockage of mPTP with Cyclosporine A (CsA) prevented the increase of mitochondrial superoxide levels, and significantly improved mitochondrial and cytosolic calcium dysregulation in AD fibroblasts. Finally, despite the failure of CsA to improve ATP levels, the inhibition of mitochondrial calcium uptake by the mitochondrial calcium uniporter increased ATP production in AD fibroblasts, indicating that these two mechanisms may contribute to mitochondrial failure in AD fibroblasts. These findings suggest that peripheral cells present similar signs of mitochondrial dysfunction observed in the brain of AD patients. Therefore, our work creates possibilities of new targets to study for early diagnosis of the AD.
Assuntos
Doença de Alzheimer/patologia , Fibroblastos/patologia , Mitocôndrias/patologia , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Trifosfato de Adenosina/metabolismo , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/metabolismo , Cálcio/metabolismo , Feminino , Fibroblastos/metabolismo , Humanos , Masculino , Potencial da Membrana Mitocondrial , Mitocôndrias/metabolismo , Poro de Transição de Permeabilidade MitocondrialRESUMO
OBJECTIVE: To assess longitudinal intrathoracic changes after fetal laser surgery in fetuses with bronchopulmonary sequestration (BPS) with hydrops and/or hydrothorax. STUDY DESIGN: The presence of intrafetal fluid effusions, the lung mass volume ratio (congenital pulmonary airway malformation volume ratio [CVR]), and the observed/expected lung-to-head circumference ratio (O/E-LHR) of both lungs were evaluated in a cohort of BPS fetuses with hydrops and/or hydrothorax treated with full laser ablation of the feeding artery (FLAFA). The longitudinal changes in intrafetal fluid effusions, lung mass volume, and pulmonary growth were analyzed by survival and multilevel analysis against days after FLAFA. RESULTS: FLAFA was successfully performed in 15 cases at a median gestational age of 26.9 weeks. A complete disappearance of the hydrops and hydrothorax was observed a median interval of 7.5 and 21 days after the fetal intervention, respectively. A progressive decrease in the CVR and an increment in the size of both lungs were observed after FLAFA. The O/E-LHR of the lung contralateral and ipsilateral to the side of the BPS became normal on average 8 and 10 weeks after FLAFA, respectively. CONCLUSION: Fetal laser surgery with FLAFA promotes disappearance of all fetal fluid effusions, a lung mass regression sequence, and a normalization of pulmonary growth.
Assuntos
Sequestro Broncopulmonar/cirurgia , Feto/cirurgia , Terapia a Laser , Tórax/diagnóstico por imagem , Sequestro Broncopulmonar/diagnóstico por imagem , Feminino , Feto/diagnóstico por imagem , Humanos , Gravidez , Estudos Prospectivos , Resultado do Tratamento , Ultrassonografia Pré-NatalRESUMO
Alzheimer's disease (AD) is characterized by the presence of aggregates of tau protein. Tau truncated by caspase-3 (D421) or tau hyperphosphorylated at Ser396/S404 might play a role in the pathogenesis of AD. Mitochondria are dynamic organelles that modify their size and function through mitochondrial dynamics. Recent studies have shown that alterations of mitochondrial dynamics affect synaptic communication. Therefore, we studied the effects of pathological forms of tau on the regulation of mitochondrial dynamics. We used primary cortical neurons from tau(-/-) knockout mice and immortalized cortical neurons (CN1.4) that were transfected with plasmids containing green fluorescent protein (GFP) or GFP with different tau forms: full-length (GFP-T4), truncated (GFP-T4C3), pseudophosphorylated (GFP-T42EC), or both truncated and pseudophosphorylated modifications of tau (GFP-T4C3-2EC). Cells expressing truncated tau showed fragmented mitochondria compared to cells that expressed full-length tau. These findings were corroborated using primary neurons from tau(-/-) knockout mice that expressed the truncated and both truncated and pseudophosphorylated forms of tau. Interestingly, mitochondrial fragmentation was accompanied by a significant reduction in levels of optic atrophy protein 1 (Opa1) in cells expressing the truncated form of tau. In addition, treatment with low concentrations of amyloid-beta (Aß) significantly reduced mitochondrial membrane potential, cell viability, and mitochondrial length in cortical cells and primary neurons from tau(-/-) mice that express truncated tau. These results indicate that the presence of tau pathology impairs mitochondrial dynamics by reducing Opa1 levels, an event that could lead to mitochondrial impairment observed in AD.
Assuntos
Doença de Alzheimer/metabolismo , Mitocôndrias/metabolismo , Dinâmica Mitocondrial/fisiologia , Neurônios/metabolismo , Proteínas tau/metabolismo , Animais , Encéfalo/metabolismo , Proteínas de Fluorescência Verde/metabolismo , Potencial da Membrana Mitocondrial/fisiologia , Camundongos , Camundongos Knockout , Fosforilação , Proteínas tau/genéticaRESUMO
Adolescence is a period of multiple changes where social behaviors influence interpersonal-relations. Adolescents live new experiences, including alcohol consumption which has become an increasing health problem. The age of onset for consumption has declined in the last decades, and additionally, the adolescents now uptake greater amounts of alcohol per occasion. Alcohol consumption is a risk factor for accidents, mental illnesses or other pathologies, as well as for the appearance of addictions, including alcoholism. An interesting topic to study is the damage that alcohol induces on the central nervous system (CNS) in the young population. The brain undergoes substantial modifications during adolescence, making brain cells more vulnerable to the ethanol toxicity. Over the last years, the brain mitochondria have emerged as a cell organelle which is particularly susceptible to alcohol. Mitochondria suffer severe alterations which can be exacerbated if the amount of alcohol or the exposure time is increased. In this review, we focus on the changes that the adolescent brain undergoes after drinking, placing particular emphasis on mitochondrial damage and their consequences against brain function. Finally, we propose the mitochondria as an important mediator in alcohol toxicity and a potential therapeutic target to reduce or treat brain conditions associated with excessive alcohol consumption.
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Consumo de Bebidas Alcoólicas/efeitos adversos , Intoxicação Alcoólica/etiologia , Encéfalo/patologia , Etanol/efeitos adversos , Mitocôndrias/patologia , Adolescente , Encéfalo/efeitos dos fármacos , Humanos , Mitocôndrias/efeitos dos fármacos , Fatores de Risco , Comportamento SocialRESUMO
Mitochondria is not only a dynamic organelle that produces ATP, but is also an important contributor to cell functions in both development and cell death processes. These paradoxical functions of mitochondria are partially regulated by the mitochondrial permeability transition pore (mPTP), a high-conductance channel that can induce loss of mitochondrial membrane potential, impairment of cellular calcium homeostasis, oxidative stress, and a decrease in ATP production upon pathological activation. Interestingly, despite their different etiologies, several neurodegenerative diseases and heart ischemic injuries share mitochondrial dysfunction as a common element. Generally, mitochondrial impairment is triggered by calcium deregulation that could lead to mPTP opening and cell death. Several studies have shown that opening of the mPTP not only induces mitochondrial damage and cell death, but is also a physiological mechanism involved in different cellular functions. The mPTP participates in regular calcium-release mechanisms that are required for proper metabolic regulation; it is hypothesized that the transient opening of this structure could be the principal mediator of cardiac and brain development. The mPTP also plays a role in protecting against different brain and cardiac disorders in the elderly population. Therefore, the aim of this work was to discuss different studies that show this controversial characteristic of the mPTP; although mPTP is normally associated with several pathological events, new critical findings suggest its importance in mitochondrial function and cell development.
Assuntos
Cardiomiopatias/patologia , Mitocôndrias/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Doenças Neurodegenerativas/patologia , Trifosfato de Adenosina/biossíntese , Animais , Cálcio/metabolismo , Coração/embriologia , Coração/crescimento & desenvolvimento , Humanos , Potencial da Membrana Mitocondrial , Camundongos , Poro de Transição de Permeabilidade Mitocondrial , Miócitos Cardíacos/citologia , Estresse Oxidativo/fisiologiaRESUMO
La sífilis es una infección de transmisión sexual (ITS) curable, causada por una bacteria llamada Treponema pallidum. Es de transmisión sexual y vertical en el embarazo. Esta patología se presenta en diferentes estadios, y cada uno se manifiesta con lesiones bucales particulares. El objetivo del presente trabajo es caracterizar las diversas manifestaciones clínicas en el período secundario aportando con imágenes propias de la experiencia en la práctica diaria. Esta etapa secundaria se expresa con gran variabilidad y multiplicidad de lesiones, lo que desorienta y crea dificultades a lahora del diagnóstico. Es de interés también actualizar el conocimiento a los profesionales de la salud y al odontólogo general sobre las pruebas serológicas que lo ayudarán a complementar y confirmar el diagnóstico de certeza.
Syphilis is a curable sexually transmitted disease (STD), caused by a bacterium called Treponema pallidum.It is transmitted sexually and vertically in pregnancy. This pathology occurs in different stages, andeach of them manifests particular oral lesions.The objective of the present article is to characterize the various clinical manifestations in the secondary period contributing with images of the experience in daily practice. This secondary stage expresses great variability and multiplicity of lesions, which is disorienting and creates difficulties when it comes to diagnosis.It is also of interest to update the knowledge for health professionals and general dentists on the serological tests that will help to complement and confirm the firm diagnosis.
Assuntos
Masculino , Feminino , Humanos , Sorodiagnóstico da Sífilis , Sífilis/diagnóstico , Infecções Sexualmente Transmissíveis/classificação , Infecções Sexualmente Transmissíveis/diagnóstico , Manifestações Bucais , Treponema pallidum/patogenicidade , Sífilis/prevenção & controle , Sífilis/epidemiologiaRESUMO
Alzheimer's disease (AD) is a multifactorial metabolic brain disorder characterized by protein aggregates, synaptic failure, and cognitive impairment. In the AD brain is common to observe the accumulation of senile plaques formed by amyloid-beta (Aß) peptide and the neurofibrillary tangles composed of modified tau protein, which both lead to cellular damage and progressive neurodegeneration. Currently, there is no effective therapy for AD; however several studies have shown that the treatments with the peroxisome proliferators activated receptor-gamma (PPARγ) agonists known as thiazolidinedione drugs (TZDs), like rosiglitazone and pioglitazone, attenuate neurodegeneration and improve cognition in mouse models and patients with mild-to-moderate AD. Furthermore, studies on animal models have shown that TZDs inhibit neuroinflammation, facilitate amyloid-ß plaque clearance, enhance mitochondrial function, improve synaptic plasticity, and, more recently, attenuate tau hyperphosphorylation. How TZDs may improve or reduce these pathologic signs of AD and what the mechanisms and the implicated pathways in which these drugs work are are questions that remain to be answered. However, in this review, we will discuss several cellular targets, in which TZDs can be acting against the neurodegeneration.
RESUMO
Alzheimer's disease (AD) is a neurodegenerative disease that affects millions of people worldwide. Currently, there is no effective treatment for AD, which indicates the necessity to understand the pathogenic mechanism of this disorder. Extracellular aggregates of amyloid precursor protein (APP), called Aß peptide and neurofibrillary tangles (NFTs), formed by tau protein in the hyperphosphorylated form are considered the hallmarks of AD. Accumulative evidence suggests that tau pathology and Aß affect neuronal cells compromising energy supply, antioxidant response, and synaptic activity. In this context, it has been showed that mitochondrial function could be affected by the presence of tau pathology and Aß in AD. Mitochondria are essential for brain cells function and the improvement of mitochondrial activity contributes to preventing neurodegeneration. Several reports have suggested that mitochondria could be affected in terms of morphology, bioenergetics, and transport in AD. These defects affect mitochondrial health, which later will contribute to the pathogenesis of AD. In this review, we will discuss evidence that supports the importance of mitochondrial injury in the pathogenesis of AD and how studying these mechanisms could lead us to suggest new targets for diagnostic and therapeutic intervention against neurodegeneration.
Assuntos
Doença de Alzheimer/patologia , Mitocôndrias/metabolismo , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Axônios/metabolismo , Encéfalo/metabolismo , Humanos , Dinâmica Mitocondrial , Proteínas tau/metabolismoRESUMO
Giardia duodenalis (syn. lamblia; syn. intestinalis) susceptibility testing is not routinely performed because the classical culture methods are very time-consuming and laborious. We developed a novel flow cytometry (FC) assay to evaluate the susceptibility of G. duodenalis trophozoites to metronidazole (MTZ). Different concentrations of MTZ were added to cultures of trophozoites (10 5 /mL) and the cultures were incubated for different periods. The 50% inhibitory concentration was calculated and propidium iodide (PI) was used to quantify the number of dead cells. After treatment, PI-positive trophozoites increased with increasing drug concentration and exposure time. An excellent correlation was found between FC and the classical method. A novel, accurate and reliable method is now available to evaluate G. duodenalis viability. .
Assuntos
Antiprotozoários/farmacologia , Giardia lamblia/efeitos dos fármacos , Metronidazol/farmacologia , Viabilidade Microbiana/efeitos dos fármacos , Citometria de Fluxo , Giardia lamblia/fisiologia , Testes de Sensibilidade Parasitária , PropídioRESUMO
Giardia duodenalis (syn. lamblia; syn. intestinalis) susceptibility testing is not routinely performed because the classical culture methods are very time-consuming and laborious. We developed a novel flow cytometry (FC) assay to evaluate the susceptibility of G. duodenalis trophozoites to metronidazole (MTZ). Different concentrations of MTZ were added to cultures of trophozoites (10 5 /mL) and the cultures were incubated for different periods. The 50% inhibitory concentration was calculated and propidium iodide (PI) was used to quantify the number of dead cells. After treatment, PI-positive trophozoites increased with increasing drug concentration and exposure time. An excellent correlation was found between FC and the classical method. A novel, accurate and reliable method is now available to evaluate G. duodenalis viability.
Assuntos
Antiprotozoários/farmacologia , Giardia lamblia/efeitos dos fármacos , Metronidazol/farmacologia , Viabilidade Microbiana/efeitos dos fármacos , Citometria de Fluxo , Giardia lamblia/fisiologia , Concentração Inibidora 50 , Testes de Sensibilidade Parasitária , PropídioRESUMO
BACKGROUND: Several countries are discussing new legislation regarding the ban on smoking in public places, based on the growing evidence of the hazards of secondhand smoke (SHS) exposure. The objective of the present study is to quantitatively assess the relationship between smoking, SHS, and serum cotinine levels in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS: From a study on lung cancer in the EPIC cohort, questionnaire information on smoking was collected at enrolment, and cotinine was measured in serum. Three statistical models were applied by using samples available in a cross-section design: (i) cotinine levels by categories combining smoking and SHS (n = 859); (ii) the effect of hours of passive smoking exposure in nonsmokers only (n = 107); (iii) the effect of the number of cigarettes consumed per day in current smokers only (n = 832). All models were adjusted for country, sex, age, and body mass index. RESULTS: Among nonsmokers, passive smokers presented significant differences in cotinine compared with nonexposed, with a marked (but not significant) difference among former-smokers. A one hour per day increment of SHS gave rise to a significant 2.58 nmol/L (0.45 ng/mL) increase in mean serum cotinine (P < 0.001). In current smokers, a one cigarette per day increment gave rise to a significant 22.44 nmol/L (3.95 ng/mL) increase in cotinine mean (P < 0.001). CONCLUSIONS: There is clear evidence that not only tobacco smoking but also involuntary exposure increases cotinine levels. IMPACT: This study strengthens the evidence for the benefits of a smoking ban in public places.