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1.
Sci Rep ; 8(1): 17369, 2018 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-30478329

RESUMO

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.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/metabolismo , Venenos de Abelha/farmacologia , Fosfolipases A2/farmacologia , Doença de Alzheimer/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Transtornos Cognitivos/tratamento farmacológico , Transtornos Cognitivos/metabolismo , Modelos Animais de Doenças , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Fragmentos de Peptídeos/farmacologia , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/metabolismo , Vacinação/métodos , Proteínas tau/metabolismo
2.
Ann Rehabil Med ; 41(4): 659-666, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28971051

RESUMO

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.

3.
Ann Rehabil Med ; 41(4): 701-704, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28971056

RESUMO

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.

4.
Auris Nasus Larynx ; 36(3): 274-9, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18786790

RESUMO

OBJECTIVES: Rhinocerebral mucormycosis is rare, rapidly progressive, potentially life-threatening disease, and it usually occurs in immunocompromised patients. We present our clinical experience with 12 cases and we attempt to identify the prognostic features and proper treatment protocols. PATIENTS AND METHODS: All the cases of mucormycosis were proven by histology or culture. The prognosis was analyzed according to the predisposing factors, including underlying disease, extent of disease and surgical intervention. RESULT: The overall mortality rate in our series was 33.3%. 7 of the 10 operated patients recovered, while 1 of the 2 non-operated patients expired. The associated conditions included diabetes mellitus (n=9) and hematological disease (n=3). A poor prognosis was primarily related with uncontrolled underlying disease. Other associated prognostic factors were the extent of disease including orbital or intracranial extension. Surgical debridement is essential for a good prognosis, but timely intervention and complete aggressive debridement are not always needed in all patients. The patient who had slowly progressive disease also survived after conventional medical management and limited surgical debridement, including orbital preservation. CONCLUSION: Control of the underlying predisposing illness along with prompt parenteral administration of amphotericin B and aggressive surgical debridement remain the essential treatments even today. Contrary to this, as described in this study, for the patients with slowly progressive disease, the aggressive surgical debridement is spared, and a successful result may be obtained with the conventional management, including medical treatment and timely limited surgical intervention.


Assuntos
Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Encefalopatias , Mucormicose , Rinite , Adulto , Idoso , Encefalopatias/tratamento farmacológico , Encefalopatias/microbiologia , Encefalopatias/cirurgia , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucormicose/complicações , Mucormicose/tratamento farmacológico , Mucormicose/cirurgia , Doenças Orbitárias/microbiologia , Doenças Orbitárias/mortalidade , Prognóstico , Rinite/tratamento farmacológico , Rinite/microbiologia , Rinite/cirurgia , Taxa de Sobrevida
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