RESUMO
Insulin-like growth factor-1 (IGF-1) and growth hormone (GH) levels are the main targets for monitoring acromegaly activity, but they are not in close relationship with the clinical course of the disease and the associated comorbidities. The present study was aimed at identifying metabolites that could be used as biomarkers for a better disease phenotyping. For this purpose, metabolic fingerprint using an untargeted metabolomic approach was examined in serum from 30 patients with acromegaly and 30 age-matched controls. Patients with acromegaly presented fewer branched-chain amino acids (BCAAs) compared to the control group (valine: 4.75 ± 0.87 vs. 5.20 ± 1.06 arbitrary units (AUs), p < 0.05; isoleucine: 2.54 ± 0.41 vs. 2.80 ± 0.51 AUs; p < 0.05). BCAAs were also lower in patients with active disease compared to patients with normal levels of IGF-1 with or without medical treatment. GH, but not IGF-1, serum levels were inversely correlated with both valine and isoleucine. These findings indicate that low levels of BCAAs represent the main metabolic fingerprint of acromegaly and that GH, rather than IGF-1, might be the primary mediator. In addition, our results suggest that the assessment of BCAAs could help to identify active disease and to monitor the response to therapeutic strategies.
RESUMO
Nanotechnology has had a significant impact on medicine in recent years, its application being referred to as nanomedicine. Nanoparticles have certain properties with biomedical applications; however, in some situations, they have demonstrated cell toxicity, which has caused concern surrounding their clinical use. In this review, we focus on two aspects: first, we summarize the types of nanoparticles according to their chemical composition and the general characteristics of their use in medicine, and second, we review the applications of nanoparticles in vascular alteration, especially in endothelial dysfunction related to oxidative stress. This condition can lead to a reduction in nitric oxide (NO) bioavailability, consequently affecting vascular tone regulation and endothelial dysfunction, which is the first phase in the development of cardiovascular diseases. Therefore, nanoparticles with antioxidant properties may improve vascular dysfunction associated with hypertension, diabetes mellitus, or atherosclerosis.
Assuntos
Vasos Sanguíneos/patologia , Nanomedicina , Nanopartículas/química , Estresse Oxidativo , Animais , Antioxidantes/metabolismo , HumanosRESUMO
BACKGROUND: Essential tremor is the most common movement disorder in adults, but its exact etiology and pathophysiology are still not fully understood. There is some consensus, however, about the involvement of the cerebellum and accumulating evidence points towards a dysfunction of the gabaergic system. We hypothesize that the serotonin neurotransmission system may also play a role as it does in tremor in Parkinson disease. This study aimed to investigate the association between the severity of tremor symptoms and the gabaergic and serotoninergic neurotransmission systems in essential tremor. MATERIAL AND METHODS: We measured the tremor clinical rating scale score and acquired DASB and Flumazenil PET scans in 10 patients who presented with essential tremor at different stages of clinical severity. Statistically significant correlations were sought between the scale scores and parametric binding potential images. RESULTS: The correlation analysis of cerebellar Flumazenil uptake and tremor clinical rating scale scores reached statistical significance (R2 = 0.423, p = 0.041), whereas no association was detected in the DASB scans. CONCLUSIONS: The severity of tremor correlated with the abnormalities found in GABA receptor binding, suggesting a primary gabaergic deficiency or a functional abnormality at the level of GABA(A) receptor subtypes. These results may assist in the rational development of new pharmacological treatments for essential tremor.
Assuntos
Tremor Essencial/metabolismo , Tremor Essencial/fisiopatologia , Neuroimagem/métodos , Serotonina/metabolismo , Ácido gama-Aminobutírico/metabolismo , Idoso , Cerebelo/diagnóstico por imagem , Cerebelo/metabolismo , Cerebelo/fisiopatologia , Tremor Essencial/diagnóstico , Feminino , Flumazenil , Humanos , Processamento de Imagem Assistida por Computador/métodos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/fisiopatologia , Tomografia por Emissão de Pósitrons/métodos , RadiografiaRESUMO
BACKGROUND AND PURPOSE: Positron emission tomography (PET) studies in humans have used (11)C-flumazenil (FMZ) to assess neuronal viability after stroke. Here we aimed to study whether (11)C-FMZ binding was sensitive to neuronal damage in the acute phase following ischemia/reperfusion in the rat brain. EXPERIMENTAL PROCEDURES: Transient (2 h followed by reperfusion) and permanent intraluminal middle cerebral artery occlusion was carried out. (11)C-FMZ binding was studied by PET up to 24 h after the onset of ischemia. Tissue infarction was evaluated post-mortem at 24 h. Immunohistochemistry against a neuronal nuclei specific protein (NeuN) was performed to assess neuronal injury. RESULTS: No decrease in (11)C-FMZ binding was detected in the ipsilateral cortex up to 24 h post-ischemia in the model of transient occlusion despite the fact that rats developed cortical and striatal infarction, and neuronal injury was clearly apparent at this time. In contrast, (11)C-FMZ binding was significantly depressed in the ipsilateral cortex at 24 h following permanent ischemia. CONCLUSIONS: This finding evidences that (11)C-FMZ binding is not sensitive to neuronal damage on the acute phase of ischemia/reperfusion in the rat brain.
Assuntos
Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/metabolismo , Degeneração Neural/diagnóstico por imagem , Degeneração Neural/metabolismo , Traumatismo por Reperfusão/diagnóstico por imagem , Traumatismo por Reperfusão/metabolismo , Doença Aguda , Animais , Sítios de Ligação/fisiologia , Isquemia Encefálica/fisiopatologia , Modelos Animais de Doenças , Flumazenil , Masculino , Degeneração Neural/fisiopatologia , Tomografia por Emissão de Pósitrons/métodos , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/fisiopatologiaRESUMO
The cleaning-up of fuel contaminated stones by submerging them in solutions of H2O2 and metallic salts is described as a mechanical process that takes 15 min to completely detach the black layer in the dark and 8 min under sunlight.