RESUMEN
Alzheimer's disease (AD) is the most common form of dementia and is characterized by an imbalance between the production and clearance of amyloid-beta (Aß) and tau proteins. Although vaccination against Aß peptide results in a dramatic reduction in Aß pathology in experimental mouse models, the initial clinical trial for an active Aß vaccine was halted early due to the development of acute meningoencephalitis in 6% of the immunized patients, which likely involved a T-cell mediated pro-inflammatory response. In this study, we aimed to determine whether bee venom phospholipase A2 (bvPLA2) treatment would induce Tregs and ameliorate AD pathology without unwanted T cell-mediated inflammation. First, we investigated the effects of bvPLA2 on the inflammatory infiltration caused by Aß vaccination. Inflammatory aggregates of CD3+ T lymphocytes and macrophages were found in the brains and spinal cords of mice treated with Aß. However, administration of bvPLA2 dramatically eliminated central nervous system inflammation following Aß immunization. In AD model mice (3xTg-AD mice), bvPLA2 administration significantly ameliorated cognitive deficits and reduced Aß burdens in the brains of Aß-vaccinated 3xTg-AD mice. Additionally, we examined brain glucose metabolism using positron emission tomography with 18F-2 fluoro-2-deoxy-D-glucose. Cerebral glucose uptake was considerably higher in the brains of Aß-vaccinated 3xTg-AD mice that received bvPLA2 than those that did not. The present study suggests that the modulation of Treg populations via bvPLA2 treatment may be a new therapeutic approach to attenuate the progression of AD in conjunction with Aß vaccination therapy without an adverse inflammatory response.
Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Péptidos beta-Amiloides/metabolismo , Venenos de Abeja/farmacología , Fosfolipasas A2/farmacología , Enfermedad de Alzheimer/metabolismo , Animales , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Trastornos del Conocimiento/tratamiento farmacológico , Trastornos del Conocimiento/metabolismo , Modelos Animales de Enfermedad , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Fragmentos de Péptidos/farmacología , Linfocitos T Reguladores/efectos de los fármacos , Linfocitos T Reguladores/metabolismo , Vacunación/métodos , Proteínas tau/metabolismoRESUMEN
OBJECTIVE: To compare the respiratory muscle strength between patients with stable and acutely exacerbated (AE) chronic obstructive pulmonary disease (COPD) at various stages. METHODS: A retrospective medical record review was conducted on patients with COPD from March 2014 to May 2016. Patients were subdivided into COPD stages 1-4 according to the Global Initiative for Chronic Obstructive Lung Disease guidelines: mild, moderate, severe, and very severe. A rehabilitation physician reviewed their medical records and initial assessment, including spirometry, maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), COPD Assessment Test, and modified Medical Research Council scale. We then compared the initial parameters in patients with a stable condition and those at AE status. RESULTS: The AE group (n=94) had significantly lower MIP (AE, 55.93±20.57; stable, 67.88±24.96; p=0.006) and MIP% (AE, 82.82±27.92; stable, 96.64±30.46; p=0.015) than the stable patient group (n=36). MIP, but not MEP, was proportional to disease severity in patients with AE and stable COPD. CONCLUSION: The strength of the inspiratory muscles may better reflect severity of disease when compared to that of expiratory muscles.
RESUMEN
Joubert syndrome (JS) is a rare genetic disorder characterized by a congenital malformation of the hindbrain, and accompanied by axonal decussation abnormalities affecting the corticospinal tract and the superior cerebellar peduncles. To the best of our knowledge, there are no reports of normal pyramidal decussation in JS. Here, we describe the case of an 18-year-old boy presenting midline-crossing corticospinal projections, which were considered normal corticospinal tract trajectories. Diffusion tensor imaging and motor evoked potential study analysis demonstrated the exclusive presence of decussating corticospinal projections in the patient. Based on these results, we suggest that JS might be associated with several, diverse corticospinal motor tract organization patterns.
RESUMEN
Atopic dermatitis (AD) is a biphasic inflammatory skin disease that is provoked by epidermal barrier defects, immune dysregulation, and increased skin infections. Previously, we have demonstrated that bvPLA2 evoked immune tolerance by inducing regulatory T cells (Treg), and thus alleviated Th2 dominant allergic asthma in mice. Here, we would like to determine whether treatment with bvPLA2 exacerbates the AD-like allergic inflammations induced by house dust mite extract (DFE) in a murine model. Epidermal thickness, immune cell infiltration, serum immunoglobulin, and cytokines were measured. Ear swelling, skin lesions, and the levels of total serum IgE and Th1/Th2 cytokines were elevated in DFE/DNCB-induced AD mice. Topical application of bvPLA2 elicited significant suppression of the increased AD symptoms, including ear thickness, serum IgE concentration, inflammatory cytokines, and histological changes. Furthermore, bvPLA2 treatment inhibited mast cell infiltration into the ear. On the other hand, Treg cell depletion abolished the anti-atopic effects of bvPLA2, suggesting that the effects of bvPLA2 depend on the existence of Tregs. Taken together, the results revealed that topical exposure to bvPLA2 aggravated atopic skin inflammation, suggesting that bvPLA2 might be a candidate for the treatment of AD.