RESUMO
Frontotemporal lobar degeneration (FTLD) belongs to a heterogeneous group of highly complex neurodegenerative diseases and represents the second cause of presenile dementia in individuals under 65. Frontotemporal-TDP is a subgroup of frontotemporal dementia characterized by the aggregation of abnormal protein deposits, predominantly transactive response DNA-binding protein 43 (TDP-43), in the frontal and temporal brain regions. These deposits lead to progressive degeneration of neurons resulting in cognitive and behavioral impairments. Limbic age-related encephalopathy (LATE) pertains to age-related cognitive decline primarily affecting the limbic system, which is crucial for memory, emotions, and learning. However, distinct, emerging research suggests a potential overlap in pathogenic processes, with some cases of limbic encephalopathy displaying TDP-43 pathology. Genetic factors play a pivotal role in both disorders. Mutations in various genes, such as progranulin (GRN) and chromosome 9 open reading frame 72 (C9orf72), have been identified as causative in frontotemporal-TDP. Similarly, specific genetic variants have been associated with an increased risk of developing LATE. Understanding these genetic links provides crucial insights into disease mechanisms and the potential for targeted therapies.
RESUMO
Demyelinating diseases alter myelin or the coating surrounding most nerve fibers in the central and peripheral nervous systems. The grouping of human central nervous system demyelinating disorders today includes multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) as distinct disease categories. Each disease is caused by a complex combination of genetic and environmental variables, many involving an autoimmune response. Even though these conditions are fundamentally similar, research into genetic factors, their unique clinical manifestations, and lesion pathology has helped with differential diagnosis and disease pathogenesis knowledge. This review aims to synthesize the genetic approaches that explain the differential susceptibility between these diseases, explore the overlapping clinical features, and pathological findings, discuss existing and emerging hypotheses on the etiology of demyelination, and assess recent pathogenicity studies and their implications for human demyelination. This review presents critical information from previous studies on the disease, which asks several questions to understand the gaps in research in this field.
Assuntos
Esclerose Múltipla , Neuromielite Óptica , Humanos , Esclerose Múltipla/patologia , Neuromielite Óptica/genética , Neuromielite Óptica/patologia , Sistema Nervoso Central/patologia , Bainha de Mielina , Diagnóstico DiferencialRESUMO
The main histopathological hallmarks of Parkinson's disease (PD) are the degeneration of the dopaminergic neurons of the substantia nigra pars compacta and the loss of neuromelanin as a consequence of decreased dopamine synthesis. The destruction of the striatal dopaminergic pathway and blocking of striatal dopamine receptors cause motor deficits in humans and experimental animal models induced by some environmental agents. In addition, neuropsychiatric symptoms such as mood and anxiety disorders, hallucinations, psychosis, cognitive impairment, and dementia are common in PD. These alterations may precede the appearance of motor symptoms and are correlated with neurochemical and structural changes in the brain. This paper reviews the most crucial pathophysiology of neuropsychiatric alterations in PD. It is worth noting that PD patients have global task learning deficits, and cognitive functions are compromised in a way is associated with hypoactivation within the striatum, anterior cingulate cortex, and inferior frontal sulcus regions. An appropriate and extensive neuropsychological screening battery in PD must accurately assess at least five cognitive domains with some tests for each cognitive domain. This neuropsychological screening should consider the pathophysiological and clinical heterogeneity of cognitive dysfunction in PD.
RESUMO
Aim: To review the main pathological findings of Neuromyelitis Optica Spectrum Disorder (NMOSD) associated with the presence of autoantibodies to aquaporin-4 (AQP4) as well as the mechanisms of astrocyte dysfunction and demyelination. Methods: An comprehensive search of the literature in the field was carried out using the database of The National Center for Biotechnology Information from . Systematic searches were performed until July 2022. Results: NMOSD is an inflammatory and demyelinating disease of the central nervous system mainly in the areas of the optic nerves and spinal cord, thus explaining mostly the clinical findings. Other areas affected in NMOSD are the brainstem, hypothalamus, and periventricular regions. Relapses in NMOSD are generally severe and patients only partially recover. NMOSD includes clinical conditions where autoantibodies to aquaporin-4 (AQP4-IgG) of astrocytes are detected as well as similar clinical conditions where such antibodies are not detected. AQP4 are channel-forming integral membrane proteins of which AQ4 isoforms are able to aggregate in supramolecular assemblies termed orthogonal arrays of particles (OAP) and are essential in the regulation of water homeostasis and the adequate modulation of neuronal activity and circuitry. AQP4 assembly in orthogonal arrays of particles is essential for AQP4-IgG pathogenicity since AQP4 autoantibodies bind to OAPs with higher affinity than for AQP4 tetramers. NMOSD has a complex background with prominent roles for genes encoding cytokines and cytokine receptors. AQP4 autoantibodies activate the complement-mediated inflammatory demyelination and the ensuing damage to AQP4 water channels, leading to water influx, necrosis and axonal loss. Conclusions: NMOSD as an astrocytopathy is a nosological entity different from multiple sclerosis with its own serological marker: immunoglobulin G-type autoantibodies against the AQP4 protein which elicits a complement-dependent cytotoxicity and neuroinflammation. Some patients with typical manifestations of NMSOD are AQP4 seronegative and myelin oligodendrocyte glycoprotein positive. Thus, the detection of autoantibodies against AQP4 or other autoantibodies is crucial for the correct treatment of the disease and immunosuppressant therapy is the first choice.
RESUMO
Melatonin, N-acetyl-5-hydroxytryptamine, is a hormone that synchronizes the internal environment with the photoperiod. It is synthesized in the pineal gland and greatly depends on the endogenous circadian clock located in the suprachiasmatic nucleus and the retina's exposure to different light intensities. Among its most studied functions are the regulation of the waking-sleep rhythm and body temperature. Furthermore, melatonin has pleiotropic actions, which affect, for instance, the modulation of the immune and the cardiovascular systems, as well as the neuroprotection achieved by scavenging free radicals. Recent research has supported that melatonin contributes to neuronal survival, proliferation, and differentiation, such as dendritogenesis and axogenesis, and its processes are similar to those caused by Nerve Growth Factor, Brain-Derived Neurotrophic Factor, Neurotrophin-3, and Neurotrophin-4/5. Furthermore, this indolamine has apoptotic and anti-inflammatory actions in specific brain regions akin to those exerted by neurotrophic factors. This review presents evidence suggesting melatonin's role as a neurotrophic factor, describes the signaling pathways involved in these processes, and, lastly, highlights the therapeutic implications involved.
Assuntos
Melatonina , Glândula Pineal , Melatonina/farmacologia , Melatonina/metabolismo , Glândula Pineal/metabolismo , Fatores de Crescimento Neural/metabolismo , Núcleo Supraquiasmático/metabolismo , Sono/fisiologia , Fator de Crescimento Transformador beta/metabolismoRESUMO
The COVID-19 pandemic has proven to be a challenge for healthcare systems, especially in terms of the care of patients with Alzheimer's disease (AD). Age is one of the major risk factors for severe forms of COVID-19, most probably due to the presence of comorbidities and inflammations. It is known that SARS-CoV-2 invades nerve endings and olfactory nerves through the binding of the spike protein to the angiotensin-converting enzyme 2 (ACE2) receptor. This interaction triggers an inflammatory cascade that results in cognitive impairment. In turn, the isoform of apolipoprotein-E4 (APOE-4ε) in AD is a risk factor for increased neuroinflammation through microglia activation, increased oxidative stress, and neurodegeneration. AD and SARS-CoV-2 are associated with increases in levels of inflammatory markers, as well as increases in levels of APOE-4ε, ACE2 and oxidative stress. Thus, there is a synergistic relationship between AD and SARS-CoV-2. In addition, the social isolation and other health measures resulting from the pandemic have led to a higher level of anxiety and depression among AD patients, a situation which may lead to a decline in cognitive function. Therefore, there is a need to develop strategies for keeping the patient calm but active.
RESUMO
Experimental autoimmune encephalomyelitis (EAE) is a relevant animal model of multiple sclerosis (MS). Oxidative stress and chronic inflammation play a major role in the pathogenesis of MS and EAE. Melatonin, a neurohormone, has potent anti-inflammatory properties. The aim of our study was to assess the therapeutic properties of melatonin alone or in combination with interferon ß-1b (IFNß-1b) or glatiramer acetate (GA) on EAE. EAE was induced in male Sprague-Dawley rats with an intraperitoneal injection of a homogenate of spinal cord and pig brain. At day 10 post immunization, rats were euthanized, and their brains were immediately excised and processed to measure oxidative stress markers and membrane fluidity. In addition, proinflammatory cytokines were quantified in plasma. Melatonin alone or in combination with GA and IFNß-1b inhibited the disease process of EAE and the synthesis of proinflammatory cytokines, caused a significant decrement in oxidative stress markers, and preserved the membrane fluidity in the motor cortex, midbrain, and spinal cord. The cumulative index score was significantly reduced in EAE rats treated with melatonin alone or in combination with GA and IFNß-1b. In conclusion, our findings provide preclinical evidence for the use of melatonin as an adjuvant therapeutic treatment for MS.
Assuntos
Encefalomielite Autoimune Experimental , Melatonina , Esclerose Múltipla , Animais , Biomarcadores , Citocinas , Encefalomielite Autoimune Experimental/patologia , Acetato de Glatiramer/farmacologia , Acetato de Glatiramer/uso terapêutico , Interferon beta-1b/uso terapêutico , Interferon beta , Masculino , Melatonina/farmacologia , Melatonina/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Ratos , Ratos Sprague-Dawley , SuínosRESUMO
BACKGROUND: Blink and masseter reflexes provide reliable, quantifiable data on the function of the central nervous system: Delayed latencies have been found in patients with neurocognitive disorder (ND) and type 2 diabetes mellitus (T2DM), but this has not been studied in patients with both pathologies. AIM: To investigate if older adults with ND plus T2DM have prolonged latencies of blink and masseter-reflex and if they were associated with disease progression. METHODS: This cross-sectional study included 227 older adults (> 60 years) from Colima, Mexico. Neurocognitive disorder was identified by a neuropsychological battery test, and T2DM identified by medical history, fasting glucose, and glycosylated hemoglobin. Latencies in the early reflex (R1), ipsilateral late (R2), and contralateral late (R2c) components of the blink reflex were analyzed for all subjects, and 183 subjects were analyzed for latency of the masseter reflex. RESULTS: In 20.7% of participants, ND was detected. In 37%, T2DM was detected. Latencies in R1, R2, and R2c were significantly prolonged for groups with ND plus T2DM, ND, and T2DM, compared with the control group (P < 0.0001). The masseter reflex was only prolonged in older adults (regardless of T2DM status) with ND vs controls (P = 0.030). In older adults with ND and without T2DM, the more the cognitive impairment progressed, the more prolonged latencies in R2 and R2c presented (P < 0.01). CONCLUSION: These findings suggest that blink and masseter reflexes could be used to evaluate possible changes in brainstem circuits in older adults with ND and T2DM.
RESUMO
Mitochondrial dysfunction and oxidative stress are extensively linked to Parkinson's disease (PD) pathogenesis. Melatonin is a pleiotropic molecule with antioxidant and neuroprotective effects. The aim of this study was to evaluate the effect of melatonin on oxidative stress markers, mitochondrial complex 1 activity, and mitochondrial respiratory control ratio in patients with PD. A double-blind, cross-over, placebo-controlled randomized clinical trial study was conducted in 26 patients who received either 25 mg of melatonin or placebo at noon and 30 min before bedtime for three months. At the end of the trial, in patients who received melatonin, we detected a significant diminution of lipoperoxides, nitric oxide metabolites, and carbonyl groups in plasma samples from PD patients compared with the placebo group. Conversely, catalase activity was increased significantly in comparison with the placebo group. Compared with the placebo group, the melatonin group showed significant increases of mitochondrial complex 1 activity and respiratory control ratio. The fluidity of the membranes was similar in the melatonin group and the placebo group at baseline and after three months of treatment. In conclusion, melatonin administration was effective in reducing the levels of oxidative stress markers and restoring the rate of complex I activity and respiratory control ratio without modifying membrane fluidity. This suggests that melatonin could play a role in the treatment of PD.
Assuntos
Antioxidantes/uso terapêutico , Antiparkinsonianos/uso terapêutico , Melatonina/uso terapêutico , Mitocôndrias/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Doença de Parkinson/tratamento farmacológico , Antioxidantes/efeitos adversos , Antiparkinsonianos/efeitos adversos , Biomarcadores/sangue , Respiração Celular/efeitos dos fármacos , Estudos Cross-Over , Método Duplo-Cego , Complexo I de Transporte de Elétrons/metabolismo , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Melatonina/efeitos adversos , México , Mitocôndrias/metabolismo , Doença de Parkinson/sangue , Doença de Parkinson/diagnóstico , Fatores de Tempo , Resultado do TratamentoRESUMO
Efficient communication between the glial cells and neurons is a bi-directional process that is essential for conserving normal functioning in the central nervous system (CNS). Neurons dynamically regulate other brain cells in the healthy brain, yet little is known about the first pathways involving oligodendrocytes and neurons. Oligodendrocytes are the myelin-forming cells in the CNS that are needed for the propagation of action potentials along axons and additionally serve to support neurons by neurotrophic factors (NFTs). In demyelinating diseases, like multiple sclerosis (MS), oligodendrocytes are thought to be the victims. Axonal damage begins early and remains silent for years, and neurological disability develops when a threshold of axonal loss is reached, and the compensatory mechanisms are depleted. Three hypotheses have been proposed to explain axonal damage: 1) the damage is caused by an inflammatory process; 2) there is an excessive accumulation of intra-axonal calcium levels; and, 3) demyelinated axons evolve to a degenerative process resulting from the lack of trophic support provided by myelin or myelin-forming cells. Although MS was traditionally considered to be a white matter disease, the demyelination process also occurs in the cerebral cortex. Recent data supports the notion that initial response is triggered by CNS injury. Thus, the understanding of the role of neuron-glial neurophysiology would help provide us with further explanations. We should take in account the suggestion that MS is in part an autoimmune disease that involves genetic and environmental factors, and the pathological response leads to demyelination, axonal loss and inflammatory infiltrates.
Assuntos
Fenômenos Eletrofisiológicos/fisiologia , Imunidade/fisiologia , Esclerose Múltipla/imunologia , Esclerose Múltipla/fisiopatologia , Oligodendroglia/fisiologia , Animais , Fenômenos Eletrofisiológicos/imunologia , Humanos , Imunidade/imunologia , Esclerose Múltipla/metabolismo , Esclerose Múltipla/patologia , Oligodendroglia/imunologia , Oligodendroglia/metabolismo , Oligodendroglia/patologiaRESUMO
High intake of omega-3 fatty acids has been associated with synaptic plasticity, neurogenesis and memory in several experimental models. To assess the efficacy of fish oil supplementation on oxidative stress markers in patients diagnosed with probable Alzheimer´s disease (AD) we conducted a double blind, randomized, placebo controlled clinical trial. AD patients who met the inclusive criteria were given fish oil (containing 0.45 g eicosapentaenoic acid and 1 g docosahexaenoic acid) or placebo daily for 12 months. Oxidative stress markers [lipoperoxides, nitric oxide catabolites levels, oxidized/reduced glutathione ratio, and membrane fluidity] and fatty acid profile in erythrocytes were assessed at enrollment, and 6 and 12 months after the start of the testing period. At the end of the trial, in patients who received fish oil, we detected a decrease in the omega 6/omega 3 ratio in erythrocyte membrane phospholipids. This change was parallel with decreases in plasma levels of lipoperoxides and nitric oxide catabolites. Conversely, the ratio of reduced to oxidized glutathione was significantly increased. In addition, membrane fluidity was increased significantly in plasma membrane samples. In conclusion fish oil administration has a beneficial effect in decreasing the levels of oxidative stress markers and improving the membrane fluidity in plasma(AU)
El alto consumo de ácidos grasos omega-3 se asocia con la plasticidad sináptica, neurogénesis y memoria en varios modelos experimentales. Para evaluar la eficacia de la suplementación con aceite de pescado en los marcadores de estrés oxidativo en pacientes con diagnóstico de la enfermedad de Alzheimer (EA) probable realizamos un ensayo clínico doble ciego, aleatorizado, controlado con placebo. A los pacientes con la EA que cumplían los criterios de inclusión se les administró aceite de pescado (que contenía 0,45 g de ácido eicosapentaenoico y 1 g de ácido docosahexaenoico) o placebo diariamente durante 12 meses. Los marcadores de estrés oxidativo plasmático [niveles de lipoperóxidos y catabolitos del óxido nítrico, cociente de glutatión reducido a glutatiónoxidado) y fluidez de la membrana] y el perfil de ácidos grasos en los eritrocitos se evaluaron al inicio, 6 meses y alos 12 meses. Al final del ensayo, en pacientes que recibieron aceite de pescado detectamos una disminución en el cociente de ácidos grasos omega 6/omega 3 en los fosfolípidos de la membrana eritrocitaria. Este cambio ocurrió en paralelo a la disminución de los niveles plasmáticos de lipoperóxidos y catabolitos del óxido nítrico. Por el contrario, el cociente de glutatión reducido a glutatión oxidado se incrementó significativamente. Además, la fluidez de la membrana aumentó significativamente en las muestras analizadas. En conclusión, la administración de aceite de pescado tiene un efecto beneficioso al disminuir los niveles de marcadores de estrés oxidativo plasmático y mejorar la fluidez de la membrana plasmática(AU)
Assuntos
Humanos , Masculino , Feminino , Óleos de Peixe , Ácidos Graxos Ômega-3 , Estresse Oxidativo , Doença de Alzheimer , Membrana Celular , Doença Crônica , NeurogêneseRESUMO
La esclerosis múltiple remitente-recurrente (EM-RR) es una enfermedad desmielinizante del sistema nervioso central. A fin de entender la asociación del estrés oxidativo a nivel periférico con la recaída de la enfermedad se determinaron los niveles de marcadores de estrés oxidativo en plasma de pacientes en la recaída o brote y una semana después de la misma. Se analizaron muestras de 60 personas (20 pacientes con recaída, 20 pacientes sin recaída y 20 controles sanos). Se cuantificaron mediante métodos espectrofotométricos las actividades enzimáticas de óxido nítrico sintasa (ONS), glutatión peroxidasa (GPx), los niveles de lipoperóxidos y nitritos-nitratos y la fluidez de membrana. En el brote de la enfermedad aumentan significativamente los niveles de las actividades enzimáticas de ONS y GPx y los niveles de nitritos-nitratos y lipoperóxidos (p<0,01 en todos los casos), al ser comparados con los de individuos sanos. Dichos parámetros disminuyeron significativamente una semana después de iniciado el brote. Además, los parámetros evaluados se mantuvieron elevados en pacientes que no experimentaron un brote de la enfermedad cuando se los comparó con individuos sanos. La fluidez de membrana en los pacientes con y sin brote fue similar a la de los controles. En conclusión, el estrés oxidativo es un componente importante en los pacientes con esclerosis múltiple.
Recurrent-remitting multiple sclerosis (RR-MS) is a demyelinating disease of the central nervous system. In order to understand the association of oxidative stress at the peripheral level with the relapse of the disease, the levels of oxidative stress markers in plasma of patients in the relapse or outbreak and one week after relapse were determined. Samples of 60 subjects were analyzed (20 patients in relapse, 20 patients without relapse, and 20 healthy controls). The enzymatic activities of nitric oxide synthase (NOS), glutathione peroxidase (GPx), lipoperoxides and nitrite-nitrate levels and membrane fluidity were quantified by spectrophotometric methods. In relapse, the levels of enzymatic activities of NOS and GPx, and the levels of lipoperoxides and nitrites-nitrates were significantly increased (p<0.01, in all cases), compared with healthy individuals. These parameters decreased significantly 1 week after the start of the outbreak. In addition, the parameters evaluated remained high in patients who did not experience an outbreak of the disease compared to healthy subjects. The membrane fluidity in the patients with and without outbreak was similar to that of the controls. In conclusion, oxidative stress is an important component in patients with multiple sclerosis.
A esclerose múltipla recorrente-remitente (EM-RR) é uma doença desmielinizante do sistema nervoso central. Para compreender a associação do estresse oxidativo a nível periférico com a recaída da doença foram determinados os níveis de marcadores de estresse oxidativo em plasma de doentes na recaída ou surto e uma semana após a recaída. Foram analisadas a amostras de 60 pessoas (20 pacientes com recaída, 20 pacientes sem recaída e 20 controles saudáveis). As atividades enzimáticas de óxido nítrico sintase (ONS), glutationa peroxidase (GPX), os níveis de lipoperóxidos e nitritos-nitratos e a fluidez de membrana foram quantificadas por métodos espectrofotométricos. No surto da doença aumentam em forma significativa os níveis da atividade enzimática de ONS e GPX, e os níveis de nitritos-nitratos e lipoperóxidos (p<0,01 em todos os casos), em comparação com os indivíduos saudáveis. Esses parâmetros diminuíram significativamente uma semana após o início do surto. Além disso, os parâmetros avaliados permaneceram elevados em pacientes que não experimentaram um surto da doença quando comparados com indivíduos saudáveis. A fluência de membrana nos pacientes com e sem surto foi semelhante à dos controles. Em conclusão, o estresse oxidativo é um componente importante nos pacientes com esclerose múltipla.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Biomarcadores/sangue , Estresse Oxidativo , Esclerose Múltipla Recidivante-Remitente/sangue , Óxido Nítrico Sintase/sangue , Glutationa Peroxidase/sangue , Peróxidos Lipídicos/sangueRESUMO
Objective: To determine the effect of melatonin (MEL) administration on ciclooxigenase 2 (COX-2) activity and serum concentration of nitric oxide metabolites, lipoperoxides and glutathione peroxidase (GPx) activity in patients with Parkinson's disease. Methods: Prospective double-blind randomized clinical pilot trial. 13 patients were included and two groups were formed: MEL at doses of 25 mg orally every 12 hours for 12 months and placebo with corn starch. Patients were assessed using the Unified Parkinson's Disease Scale. A blood sample was taken at baseline and every 3 months until 12 months. Results: COX-2 activity decreased as did nitrates/nitrites (3, 6 and 9 months) and lipoperoxides (9 and 12 months); GPx exhibited no significant differences.
Assuntos
Antioxidantes/farmacologia , Ciclo-Oxigenase 2/metabolismo , Glutationa Peroxidase/sangue , Peróxidos Lipídicos/sangue , Melatonina/farmacologia , Óxido Nítrico/metabolismo , Doença de Parkinson/metabolismo , Antioxidantes/administração & dosagem , Método Duplo-Cego , Humanos , Melatonina/administração & dosagem , Estresse Oxidativo , Projetos Piloto , Estudos ProspectivosRESUMO
Parkinson's disease (PD), its prevalent in population to 65 years of age, nevertheless can occur earlier. Patients with PD exhibit motor and no motor symptoms these may relate with changes in nutritional habits during disease progression. The prevalence of PD and nutritional factor could be different in rural areas compared to urban regions and can be associated with sociocultural and demographic features. It has been suggested a possible association between excessive intake of saturated fats and low consumption of vitamins such as B6 with EP, however, the results are still not conclusive. Some of significant factors could affect nutritional habits and status in PD in rural areas, are: health status, economic availability, environmental and geographical factors, among others. This review presents some eating habits and sociodemographic factors in PD principally in rural areas.
La enfermedad de Parkinson (EP) predomina en la población de 65 años de edad o más y se caracteriza tanto por síntomas motores como no motores, los cuales pueden asociarse con cambios en la conducta alimentaria. Los factores nutricionales pueden depender de las características socioculturales y sociodemográficas, y esto a su vez podrían ser diferente en el medio rural en comparación con el medio urbano. Se ha propuesto una posible asociación entre el exceso en la ingesta de grasas saturadas y la baja ingesta de vitaminas como la B6 y los antioxidantes con la EP; sin embargo, los resultados aún no son concluyentes. Entre los factores significativos que podrían afectar a los hábitos nutricionales y condicionar el estado nutricional en la EP en zonas rurales se encuentran: el estado de salud, la disponibilidad económica, los factores ambientales y geográficos, entre otros. La presente revisión analiza algunos de los hábitos alimentarios y los factores sociodemográficos en la EP, principalmente en zonas rurales.
Assuntos
Estado Nutricional , Doença de Parkinson/epidemiologia , População Rural , Idoso , Idoso de 80 Anos ou mais , Dieta , Comportamento Alimentar , Feminino , Humanos , Masculino , México/epidemiologia , Fatores SocioeconômicosRESUMO
The development of probes for biomedical applications demands materials with low toxicity levels besides fluorescence or magnetic properties to be detected by confocal microscopes or MRI resonators. Several drug delivery systems or other biomedical materials prepared with hydroxyapatite have been proposed, however, toxicity effects might arise when the size of particles is nanometric. In this study, hydroxyapatite functionalized with glucuronic or folic acids presented lower oxidative stress, measured from lipoperoxides and nitric oxide indicators in rats than pure hydroxyapatite. In separated experiments, hydroxyapatite was doped with dysprosium cations by coprecipitation producing a single crystal phase with fluorescent properties easily visualized by confocal microscopy when excited at 488nm. These particles also presented the ability to modify the proton relaxation time in T1 maps collected by magnetic resonance imaging. These modified hydroxyapatite nanoparticles could be candidates to design bimodal probes with low toxicity.
Assuntos
Durapatita , Disprósio , Ácido Fólico , Ácido Glucurônico , Animais , Durapatita/efeitos adversos , Durapatita/química , Durapatita/farmacocinética , Durapatita/farmacologia , Disprósio/efeitos adversos , Disprósio/química , Disprósio/farmacocinética , Disprósio/farmacologia , Ácido Fólico/efeitos adversos , Ácido Fólico/química , Ácido Fólico/farmacocinética , Ácido Fólico/farmacologia , Ácido Glucurônico/efeitos adversos , Ácido Glucurônico/química , Ácido Glucurônico/farmacocinética , Ácido Glucurônico/farmacologia , Imageamento por Ressonância Magnética , Microscopia de Fluorescência , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-DawleyRESUMO
Mitochondrial dysfunction has been thought to contribute to Alzheimer disease (AD) pathogenesis through the accumulation of mitochondrial DNA mutations and net production of reactive oxygen species (ROS). Mitochondrial cytochrome c-oxidase plays a key role in the regulation of aerobic production of energy and is composed of 13 subunits. The 3 largest subunits (I, II, and III) forming the catalytic core are encoded by mitochondrial DNA. The aim of this work was to look for mutations in mitochondrial cytochrome c-oxidase gene II (MTCO II) in blood samples from probable AD Mexican patients. MTCO II gene was sequenced in 33 patients with diagnosis of probable AD. Four patients (12%) harbored the A8027G polymorphism and three of them were early onset (EO) AD cases with familial history of the disease. In addition, other four patients with EOAD had only one of the following point mutations: A8003C, T8082C, C8201T, or G7603A. Neither of the point mutations found in this work has been described previously for AD patients, and the A8027G polymorphism has been described previously; however, it hasn't been related to AD. We will need further investigation to demonstrate the role of the point mutations of mitochondrial DNA in the pathogenesis of AD.
RESUMO
Introducción: las intervenciones durante el tratamiento en el paciente oncológico, aumentan los riesgos para sufrir una infección nosocomial. En el Instituto Jalisciense de Cancerología, la prevención, identificación y seguimiento de las infecciones nosocomiales se realiza a través del programa de epidemiologia y por el Comité de Vigilancia Epidemiológica. Objetivos: determinar la incidencia de infecciones nosocomiales en pacientes oncológicos atendidos en el citado instituto. Métodos: se trata de un estudio descriptivo retrospectivo. Se tomaron en cuenta 5 056 egresos de abril de 2008 a diciembre de 2010, de los cuales 140 pacientes presentaron 178 infecciones nosocomiales. Resultados: la tasa global de infecciones por 100 egresos, fue variable (2008: 5,8; en 2009: 3,5 y en 2010: 2,2). La infección de herida quirúrgica se mantuvo con las tasas más altas (2,9; 1,5; 1,1). El germen más frecuentemente aislado fue Escherichia coli (55 %, 34 %, 20 %), el hongo más frecuente fue la Candida albicans (6 %, 7 %, 6 %). El promedio días estancia en el momento de la captación de la infección, fue de 3,3 días y en el momento del egreso fue de 17 días. La tasa de letalidad, fue de 19 por cada 100 casos, y la tasa de mortalidad 27 por cada 100 casos. Conclusiones: se observa una disminución en la tasa de infección nosocomial en los últimos años. La intervención del Servicio de Epidemiología con sus acciones dirigidas de manera específica, al manejo de las heridas quirúrgicas, es fundamental.
Background: the treatments in cancer patients increase the risk of catching nosocomial infection. In the Instituto Jalisciense de Cancerología, the prevention, identification and monitoring of nosocomial infections is carried out by the Epidemiological Surveillance Committee through an epidemiological program. Objectives: To determine the incidence of nosocomial infections in cancer patients seen at the Instituto Jalisciense de Cancerología Methods: A retrospective and descriptive study, which included 5056 patients discharged from April 2008 to December 2010, of whom 140 had nosocomial infections. Results: The overall rate of infections per 100 discharges was variable (5.8 in 2008; 3.5 in 2009 and 2.2 in 2010). The surgical wound infection kept the highest rates (2.9, 1.5, 1.1 respectively). The most common isolated bacteria was Escherichia coli (55 %, 34 %, 20 %); the most frequent fungus was Candida albicans (6 %, 7 %, 6 %). The average length of stay at the time of catching the infection was 3.3 days, and at the time of hospital discharge was 17 days. The fatality rate was 19 per 100 cases whereas the mortality rate was 27 per 100 cases. Conclusions: a decrease in the rate of nosocomial infection was observed in recent years; where the epidemiology service was the key to implementing epidemiological actions, in particular the management of surgical wounds.
RESUMO
Los estudios sobre los efectos del envejecimiento en la fisiología y el metabolismo cada vez son más, uno de sus objetivos es contribuir a instrumentar programas para mejorar la calidad de vida y prevenir discapacidades en la vejez. Es de gran importancia mencionar que durante el envejecimiento se presenta una desaceleración natural del metabolismo, se produce una serie de cambios en la regulación de la energía, lo que contribuye a la pérdida de peso y grasa; estos cambios en la regulación de la ingesta calórica contribuyen en un aumento de la susceptibilidad al desequilibrio energético tanto positivo como negativo, lo cual va asociado a un deterioro en la salud. Sin embargo, el llegar a la vejez, no es una sentencia de muerte para el metabolismo, por el contrario, éste puede ser controlado mediante el mantenimiento de un estilo de vida activo, aunado a esto investigaciones han demostrado que el metabolismo puede ser regulado mediante el papel que desempeña un sistema de reloj sincronizado (ritmos biológicos), el cual a su vez es modulado por varias proteínas reguladoras; esta relación garantiza que las células funcionen correctamente y por tanto el mantenerse saludables. El objetivo de esta revisión es aportar información actualizada sobre la regulación metabolismo-energía y su relación con la gran variedad de componentes involucrados en el gasto energético que acompañan al envejecimiento; analizar la regulación de este sistema para mejorar la calidad de vida y mantener la salud en la vejez.
Aging and metabolism: changes and regulation. Studies about the effects of aging in the physiology and metabolism are increasingly, one of its objectives is to help implement programs to improve the quality of life and prevent disability in elderly. It is relevant to mention that, during aging, there is a natural metabolic deceleration, a series of changes in the regulation of energy are produced, which contributes to loss of weight and fat; the changes in the regulation of caloric intake contribute to increase the susceptibility to energy imbalance both positive and negative, which is associated with a deterioration in health. However, to grow old, is not a death sentence for metabolism, on the other hand, it can be controlled by maintaining an active lifestyle, coupled with this, research has shown that the metabolism can be regulated by a synchronized clock (circadian rhythms), which is mediated by regulatory proteins, this relationship ensures the proper functioning of the cells and therefore good health. The aim of this review is to provide updated information on the energy- metabolism-regulation and its relationship with the great variety of components involved in energy expenditure that accompany aging, to analyze the regulation of this system to improve the quality of life and maintenance of health in old age.
Assuntos
Idoso , Idoso de 80 Anos ou mais , Humanos , Envelhecimento/metabolismo , Ingestão de Energia/fisiologia , Metabolismo Energético/fisiologia , Ritmo Circadiano/fisiologia , Comportamento Alimentar/fisiologia , Estado NutricionalRESUMO
PURPOSE: To determine the prevalence of disability in Basic Activities of Daily Living and Instrumental Activities of Daily Living (ADL and IADL, respectively), as well as associated factors in the Mexican community-dwelling elderly population. MATERIALS AND METHODS: This is a cross-sectional study of a population 60 years and older who live in the State of Jalisco (Mexico). A total of 2553 persons were assessed regarding their functional and health conditions. The ADL and IADL were classified as dependent and non-dependent, and crude and adjusted Odds Ratio (OR) were calculated. RESULTS: Mean age of participants was 71.6±8.7, 61.2% were women. A disability prevalence of 9.6% was found to perform ADL and of 31.5% for the IADL, 14.3% had cognitive impairment and 30.9% depression. Risk factors were found for dependence: being a woman, being ≥75 years old, low education level, having at least one chronic disease, cognitive impairment, depression, previous history of disability, and having been a lifelong housewife. CONCLUSIONS: Functional difficulties are common in Mexican elderly population. These data show key variables for functional disability risk. A better understanding of functional capabilities, as well as of risk factors older adults face every day provide us with a guide to devise a prevention plan, to implement adequate interventions, or to provide appropriate care.
Assuntos
Atividades Cotidianas , Características de Residência/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Transtornos Cognitivos/epidemiologia , Estudos Transversais , Depressão/epidemiologia , Feminino , Nível de Saúde , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , PrevalênciaRESUMO
Studies about the effects of aging in the physiology and metabolism are increasingly, one of its objectives is to help implement programs to improve the quality of life and prevent disability in elderly. It is relevant to mention that, during aging, there is a natural metabolic deceleration, a series of changes in the regulation of energy are produced, which contributes to loss of weight and fat; the changes in the regulation of caloric intake contribute to increase the susceptibility to energy imbalance both positive and negative, which is associated with a deterioration in health. However, to grow old, is not a death sentence for metabolism, on the other hand, it can be controlled by maintaining an active lifestyle, coupled with this, research has shown that the metabolism'can be regulated by a synchronized clock (circadian rhythms), which is mediated by regulatory proteins, this relationship ensures the proper functioning of the cells and therefore good health. The aim of this review is to provide updated information on the energy- metabolism-regulation and its relationship with the great variety of components involved in energy expenditure that accompany aging, to analyze the regulation of this system to improve the quality of life and maintenance of health in old age.