RESUMO
A 61-year-old woman presented to the emergency room complaining of anterior left thoracic pain and shortness of breath even after minor efforts. Her previous medical history was unremarkable. Pulmonary angiographic tomography showed a moderate bilateral pleural effusion that had collapsed inferior lung lobes, a large pericardial effusion, and several enlarged lymph nodes in the anterior mediastinum. Echocardiogram (ECG) showed a considerable pericardial effusion with some degree of heart function impairment. Pericardiocentesis and thoracocentesis revealed neoplastic cells in both pericardial and pleural fluids. Abdominal and pelvic ultrasound showed a complex cystic mass with a 13-cm diameter located at left adnexal region and another complex cystic tumor with five-cm diameter at right adnexal region, with small amount of peritoneal effusion. Surgical staging was performed. Pathologic diagnosis was primitive left fallopian tube serous adenocarcinoma with peritubal involvement and multiple peritoneal and lymphatic metastases (FIGO Stage IV; TNM pT3c M1). Chemotherapy was initiated. Death occurred 25 months after diagnosis, with secondary dissemination (breast and lung). No recurrence of pericardial effusion was registered after chemotherapy, suggesting a high susceptibility of pericardial metastasis.
Assuntos
Tamponamento Cardíaco/etiologia , Cistadenocarcinoma Seroso/complicações , Neoplasias das Tubas Uterinas/complicações , Cistadenocarcinoma Seroso/terapia , Neoplasias das Tubas Uterinas/terapia , Feminino , Neoplasias Cardíacas/secundário , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Pericárdio/patologiaRESUMO
BACKGROUND: Classification defined in the Trial of Org10172 in Acute Ischaemic Stroke (TOAST) is widely used in trials and practice. Previous studies on pathophysiology suggest a role for endothelial inflammation in atherothrombotic strokes and intracardiac thrombosis in cardioembolic strokes. Data on lacunar and undetermined strokes are limited. The aim of the study was to assess non-specific inflammatory and thrombogenic parameters in patients with ischaemic stroke. METHODS: This was a prospective controlled clinical study involving 200 patients with ischaemic stroke and 50 controls. Patients were classified following the TOAST criteria. Plasma levels of fibrinogen, D-dimer, C reactive protein and values for D-dimer/fibrinogen ratio and erythrocyte sedimentation rate were assessed over 48 h after admission. Clinical severity was measured using the National Institutes of Health Stroke Scale and the Oxfordshire Community Stroke Project classification. Patients with severe systemic disorders were excluded. RESULTS: The assessed parameters were significantly higher in patients versus controls. Cardioembolic stroke patients showed increased D-dimer, fibrinogen and D-dimer/fibrinogen ratio. Patients with atherothrombotic stroke showed raised fibrinogen and erythrocyte sedimentation rate. Patients with lacunar and undetermined stroke showed intermediate values of markers. Total anterior cerebral infarction syndrome was related to D-dimer. DISCUSSION: Patients showed analytical modifications during the acute phase of stroke, both related to acute response and mechanism. The results suggest that the biochemical profile may be prothrombotic in patients with cardioembolism and inflammatory in those with atherothrombotic stroke. Patients with lacunar and undetermined stroke showed intermediate profiles. Assessment of the studied parameters is not expensive, widely available and may proportionate information about pathophysiology in stroke patients without severe systemic conditions.
Assuntos
Sedimentação Sanguínea , Isquemia Encefálica/sangue , Isquemia Encefálica/fisiopatologia , Proteína C-Reativa/análise , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Fibrinogênio/análise , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/fisiopatologia , Idoso , Biomarcadores , Pressão Sanguínea/fisiologia , Eletrocardiografia , Embolia/sangue , Embolia/complicações , Embolia/fisiopatologia , Feminino , Humanos , Inflamação/sangue , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores Socioeconômicos , Trombose/sangueRESUMO
BACKGROUND: Lower level of albumin was related to worse prognosis of stroke and clinical trials showed that albumin therapy reduced mortality. However, stroke is heterogeneous and differences in the baseline concentration of albumin among subtypes of stroke were not assessed. The aim was to assess albumin level in patients with ischemic stroke classified by mechanism. METHODS: Prospective controlled clinical study, including 200 patients with ischemic stroke and 50 controls. Patients were classified following Trial of ORG 10172 in Acute Stroke Treatment criteria. Plasma levels of albumin, fibrinogen, D-dimer, and C-reactive protein were assessed during 48 hr after admission. The National Institutes of Health Stroke Scale (NIHSS) on admission, in-hospital mortality, and Rankin score on discharge were recorded. Dependence was defined as mRS > 2. RESULTS: Patients with cardioembolic stroke showed significantly higher D-dimer and lower albumin. Mortality was related to higher NIHSS, higher D-dimer, lower albumin, and cardioembolic aetiology. Dependence was strongly related to lower albumin and higher NIHSS. LOGISTIC REGRESSION: The cardioembolic aetiology (OR 0.101, 95% CI 0.010-1.007, p = .051) and the higher NIHSS score (OR 0.871, 95% CI 0.758-1.002, p = .053) were related to mortality; NIHSS (OR 1.560, 95% CI 1.323-1.838, p < .0001) and older age (OR 1.052, 95% CI 1.012-1.093, p = .010) were independently related to dependence. DISCUSSION: Patients with cardioembolic stroke showed lower albumin and higher risk of mortality than non-cardioembolic ones. Lower mean level of albumin was related to mortality and dependence in all patients. Reduced albumin may be a marker of chronic systemic inflammation, which may be the mechanism for cardiopathy and bad outcome of stroke. In addition, direct effects on ischemic tissue were suggested in experimental models.
Assuntos
Isquemia Encefálica/diagnóstico , Isquemia Encefálica/metabolismo , Embolia/metabolismo , Albumina Sérica/metabolismo , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/metabolismo , Idoso , Biomarcadores/sangue , Isquemia Encefálica/complicações , Isquemia Encefálica/mortalidade , Proteína C-Reativa/metabolismo , Embolia/complicações , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Fibrinogênio/metabolismo , Mortalidade Hospitalar , Humanos , Masculino , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/mortalidadeAssuntos
Papel do Médico , Médicos/psicologia , Abandono do Hábito de Fumar/psicologia , Fumar/psicologia , Adulto , Congressos como Assunto , Coleta de Dados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Médicos/estatística & dados numéricos , Portugal/epidemiologia , Distribuição por Sexo , Fumar/epidemiologia , Abandono do Hábito de Fumar/estatística & dados numéricosRESUMO
Nonalcoholic fatty liver disease (NAFLD) is caused by excessive liver lipid accumulation, but insulin resistance is specifically associated with impaired lipid saturation, oxidation, and storage (esterification), besides increased de novo lipogenesis. We hypothesized that dietary glycotoxins could impair hepatic lipid metabolism in obesity contributing to lipotoxicity-driven insulin resistance and thus to the onset of nonalcoholic steatohepatitis (NASH). In diet-induced obese rats with methylglyoxal-induced glycation, magnetic resonance spectroscopy, mass spectrometry, and gas chromatography were used to assess liver composition in fatty acyl chains and phospholipids. High-fat diet-induced obesity increased liver lipid fraction and suppressed de novo lipogenesis but did not change fatty acid esterification and saturation or insulin sensitivity. Despite a similar increase in total lipid fraction when supplementing the high-fat diet with dietary glycotoxins, impairment in the suppression of de novo lipogenesis and decreased fatty acid unsaturation and esterification were observed. Moreover, glycotoxins also decreased polyunsaturated cardiolipins and caused oxidative stress, portal inflammation, and insulin resistance in high-fat diet-induced obese rats. Dietary glycated products do not change total lipid levels in the liver of obese rats but dramatically modify the lipidemic profile, leading to oxidative stress, hepatic lipotoxicity, and insulin resistance in obesity and thus contribute to the onset of NASH.
Assuntos
Dieta Hiperlipídica/efeitos adversos , Hepatopatia Gordurosa não Alcoólica/complicações , Obesidade/patologia , Animais , Resistência à Insulina , Metabolismo dos Lipídeos , Masculino , Estresse Oxidativo , Ratos , Ratos WistarRESUMO
BACKGROUND: amyloid-PET reading has been classically implemented as a binary assessment, although the clinical experience has shown that the number of borderline cases is non negligible not only in epidemiological studies of asymptomatic subjects but also in naturalistic groups of symptomatic patients attending memory clinics. In this work we develop a model to compare and integrate visual reading with two independent semi-quantification methods in order to obtain a tracer-independent multi-parametric evaluation. METHODS: We retrospectively enrolled three cohorts of cognitively impaired patients submitted to 18F-florbetaben (53 subjects), 18F-flutemetamol (62 subjects), 18F-florbetapir (60 subjects) PET/CT respectively, in 6 European centres belonging to the EADC. The 175 scans were visually classified as positive/negative following approved criteria and further classified with a 5-step grading as negative, mild negative, borderline, mild positive, positive by 5 independent readers, blind to clinical data. Scan quality was also visually assessed and recorded. Semi-quantification was based on two quantifiers: the standardized uptake value (SUVr) and the ELBA method. We used a sigmoid model to relate the grading with the quantifiers. We measured the readers accord and inconsistencies in the visual assessment as well as the relationship between discrepancies on the grading and semi-quantifications. CONCLUSION: It is possible to construct a map between different tracers and different quantification methods without resorting to ad-hoc acquired cases. We used a 5-level visual scale which, together with a mathematical model, delivered cut-offs and transition regions on tracers that are (largely) independent from the population. All fluorinated tracers appeared to have the same contrast and discrimination ability with respect to the negative-to-positive grading. We validated the integration of both visual reading and different quantifiers in a more robust framework thus bridging the gap between a binary and a user-independent continuous scale.
Assuntos
Doença de Alzheimer/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Placa Amiloide/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/metabolismo , Encéfalo/metabolismo , Estudos de Coortes , Europa (Continente)/epidemiologia , Feminino , Radioisótopos de Flúor/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Placa Amiloide/metabolismo , Tomografia por Emissão de Pósitrons/tendências , Estudos RetrospectivosRESUMO
Blood-brain barrier (BBB) permeability in type 2 diabetic patients has been previously shown to be altered in certain brain regions such as the basal ganglia and the hippocampus. Because of the histological and functional similarities between the BBB) and the blood-retinal barrier (BRB), we aimed to investigate how the permeability of both barriers predicts visual outcome. We included 2 control groups (acute unilateral stroke patients, n = 9; type 2 diabetics without BRB leakage n = 10) and a case study group of type 2 diabetics with established BRB leakage (n = 17). We evaluated sex, age, disease duration, metabolic impairment, retinopathy grade and BBB permeability as predictors of visual acuity at baseline, 12 and 24 months in the type 2 diabetics without BRB leakage group and the case study group. We have also explored differences in BBB permeability in the occipital lobe and frontal lobe in the 3 different groups. Ktrans (volume transfer coefficient) and Vp (fractional plasma volume) were estimated. The BBB permeability parameter Vp was higher in the case study group compared to the unaffected hemisphere of the stroke patient control group, suggesting vascular dynamics were changed in the occipital lobe of type 2 diabetics with established BRB leakage. These patients showed a significant correlation between glycated hemoglobin (HbA1C) levels and occipital and frontal Ktrans . We report for the first time that occipital BBB permeability is an independent predictor of visual acuity at baseline, as well as at 12 and 24 months, in type 2 diabetics with established BRB leakage. Our results suggest that occipital BBB permeability might be an independent biomarker for visual impairment in patients with established BRB leakage.
Assuntos
Barreira Hematoencefálica/metabolismo , Barreira Hematorretiniana/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Retinopatia Diabética/metabolismo , Lobo Occipital/metabolismo , Retina/metabolismo , Fatores Etários , Idoso , Barreira Hematoencefálica/patologia , Barreira Hematorretiniana/patologia , Diabetes Mellitus Tipo 2/patologia , Retinopatia Diabética/patologia , Feminino , Lobo Frontal/metabolismo , Lobo Frontal/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Lobo Occipital/patologia , Permeabilidade , Prognóstico , Retina/patologia , Fatores SexuaisRESUMO
OBJECTIVE: Deregulated apoptosis might be involved in some of the features of Fanconi anaemia (FA). The possibility that the pro-apoptotic Bax protein could be involved in an increased susceptibility to apoptosis in FA patients was investigated. MATERIALS AND METHODS: Intracellular Bax expression, Bcl-2 expression (an anti-apoptotic protein) and cell death were analysed in 26 FA peripheral blood lymphocyte samples. RESULTS: Most FA samples (69%) displayed increased levels of Bax and were more susceptible to both spontaneous apoptosis and mitogen activation-induced cell death. Two subgroups were identified: one presented elevated levels of Bax (n = 18), whereas the other (n = 8), had Bax levels lower than controls. Two subgroups based on Bcl-2 expression were also identified: one with normal and another with high Bcl-2 expression. No inverse correlation was found between Bcl-2 levels and Bax expression. A clear difference in susceptibility to induced cell death could be observed between control and FA samples. The best correlation was observed between high levels of Bax and mitogen-induced apoptosis of cells; these displayed characteristics of necrosis secondary to apoptosis, suggesting that the intrinsic apoptotic pathway was being activated. CONCLUSION: Despite increased susceptibility to cell death induction, there was no correlation between Bax levels, chromosome breakage, haematological parameters or androgen therapy. The importance of apoptosis and Bax expression in the clinical development of FA awaits clarification.
Assuntos
Apoptose , Anemia de Fanconi/metabolismo , Proteína X Associada a bcl-2/metabolismo , Adolescente , Adulto , Células Cultivadas , Criança , Pré-Escolar , Anemia de Fanconi/sangue , Anemia de Fanconi/patologia , Humanos , Linfócitos/metabolismo , Linfócitos/patologia , Proteína X Associada a bcl-2/sangueRESUMO
Agrimony (Agrimonia eupatoria L.) (Ae) is used in traditional medicine to treat inflammatory and oxidative related diseases. Therefore, this study focuses on the anti-inflammatory and analgesic potential of Ae infusion (AeI). Phenolic compounds characterization was achieved by HPLC-PDA-ESI/MS n . To evaluate antioxidant potential, 2,2-diphenyl-1-picrylhydrazyl (DPPH), superoxide anion, hydroxyl radical, and SNAP assays were used. In vitro anti-inflammatory activity of AeI was investigated in LPS-stimulated macrophages by measuring the NO production. In vivo anti-inflammatory activity was validated using the mouse carrageenan-induced paw edema model. Peripheral and central analgesic potential was evaluated using the acetic acid-induced writhing and hot-plate tests, respectively, as well as the formalin assay to assess both activities. The safety profile was disclosed in vitro and in vivo, using MTT and hematoxylin assays, respectively. Vitexin, quercetin O-galloyl-hexoside, and kaempferol O-acetyl-hexosyl-rhamnoside were referred to in this species for the first time. AeI and mainly AePF (Ae polyphenolic fraction) showed a significant antiradical activity against all tested radicals. Both AeI and AePF decreased NO levels in vitro, AePF being more active than AeI. In vivo anti-inflammatory and analgesic activities were verified for both samples at concentrations devoid of toxicity. Agrimony infusion and, mainly, AePF are potential sources of antiradical and anti-inflammatory polyphenols.
RESUMO
Progressive supranuclear palsy (PSP) is a neurodegenerative disorder showing predominant brainstem involvement, characterized by marked slowing of rapid eye movements (saccades), particularly along the vertical plane. While the contribution of the brainstem damage for the saccadic disturbance in PSP has been extensively studied, much less is known about its cortical and subcortical pathomechanisms. We measured reflexive (prosaccades) and voluntary (antisaccades) saccades in the vertical and horizontal plane in PSP patients (n=8) and controls (n=10) in an eye tracking study, followed by the measurement of blood oxygenation-level dependent (BOLD) activation (PSP, n=6; controls, n=10) during similar saccade paradigms. Behaviorally, PSP patients evidenced slower and lower amplitude prosaccades (horizontal and vertical) and lower amplitude antisaccades (vertical) than controls. Functionally, patients showed decreased frontostriatal BOLD activation during prosaccades (horizontal and vertical) and antisaccades (vertical), relative to controls. Additionally, PSP patients showed less default mode network (DMN) deactivation than controls for all types of saccades. Within groups, controls showed no BOLD differences between horizontal and vertical prosaccades while PSP patients demonstrated greater DMN deactivation during vertical prosaccades. Both groups evidenced greater DMN deactivation during vertical antisaccades when compared to their horizontal counterpart and patients further showed relative frontostriatal BOLD hypoactivity during vertical antisaccades. We found fMRI evidence of frontostriatal hypoactivity in PSP patients relative to controls, especially during vertical saccades. These new findings highlight the impact of cortical impairment in saccadic disturbance of PSP.
Assuntos
Córtex Cerebral/fisiopatologia , Movimentos Sacádicos/fisiologia , Paralisia Supranuclear Progressiva/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Mapeamento Encefálico , Córtex Cerebral/diagnóstico por imagem , Circulação Cerebrovascular/fisiologia , Medições dos Movimentos Oculares , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiopatologia , Testes Neuropsicológicos , Oxigênio/sangue , Paralisia Supranuclear Progressiva/diagnóstico por imagemRESUMO
Sensory deficits have been documented in Parkinson's disease, in particular within the visual domain. However, ageing factors related to the brain and to neural and non-neural ocular structures could explain some of the previously reported results, in particular the claimed impairment within the koniocellular pathway. This study addressed visual impairment attributable to the magno- (luminance), parvo- (red-green) and koniocellular (blue-yellow) pathways in a population of Parkinson's disease patients. To avoid potentially confounding factors, all subjects underwent a full neurophthalmological assessment which led to exclusion of subjects with increased intraocular pressure, diabetes even in the absence of retinopathy, and ocular abnormalities (from a total of 72 patients' eyes, 12 were excluded). Both parvo- and koniocellular pathways were studied by means of contrast sensitivity (CS) measurements along protan, tritan and deutan axes and also by fitting chromatic discrimination ellipses using eight measured contrast axes. Magnocellular function was assessed, using stimuli that induce a frequency doubling illusion, in 17 locations in the fovea and periphery. Achromatic (luminance modulation) thresholds were significantly higher in Parkinson's disease both in foveal and peripheral locations. A significant impairment was observed along protan and deutan axes, but only marginally along the tritan axis. These results were corroborated by a significant elongation of chromatic discrimination ellipses in our Parkinson's disease group. Correlation analysis showed that achromatic and chromatic CS measures were independent, which implies that multiple visual pathways are affected independently in Parkinson's disease. Magnocellular impairment was significantly correlated with age and disease stage, in contrast to the measured chromatic deficits. We conclude that in Parkinson's disease, independent damage occurs in the early magno- and parvocellular pathways. Furthermore, traditional koniocellular probing strategies in Parkinson's disease may be confounded by ageing factors, which may reconcile the previously reported controversial findings concerning chromatic impairment in Parkinson's disease.
Assuntos
Doença de Parkinson/fisiopatologia , Transtornos da Visão/fisiopatologia , Envelhecimento/fisiologia , Percepção de Cores/fisiologia , Sensibilidades de Contraste/fisiologia , Feminino , Fóvea Central/patologia , Fóvea Central/fisiopatologia , Humanos , Ilusões/fisiologia , Masculino , Pessoa de Meia-Idade , Vias Neurais/patologia , Vias Neurais/fisiopatologia , Doença de Parkinson/complicações , Doença de Parkinson/patologia , Estimulação Luminosa/métodos , Psicofísica , Retina/patologia , Retina/fisiopatologia , Limiar Sensorial/fisiologia , Transtornos da Visão/etiologia , Transtornos da Visão/patologia , Percepção Visual/fisiologiaRESUMO
Neurofibromatosis type-1 (NF1) is a common neurogenetic disorder and an important cause of intellectual disability. Brain-behaviour associations can be examined in vivo using morphometric magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) to study brain structure. Here, we studied structural and behavioural phenotypes in heterozygous Nf1 mice (Nf1(+/-) ) using T2-weighted imaging MRI and DTI, with a focus on social recognition deficits. We found that Nf1(+/-) mice have larger volumes than wild-type (WT) mice in regions of interest involved in social cognition, the prefrontal cortex (PFC) and the caudate-putamen (CPu). Higher diffusivity was found across a distributed network of cortical and subcortical brain regions, within and beyond these regions. Significant differences were observed for the social recognition test. Most importantly, significant structure-function correlations were identified concerning social recognition performance and PFC volumes in Nf1(+/-) mice. Analyses of spatial learning corroborated the previously known deficits in the mutant mice, as corroborated by platform crossings, training quadrant time and average proximity measures. Moreover, linear discriminant analysis of spatial performance identified 2 separate sub-groups in Nf1(+/-) mice. A significant correlation between quadrant time and CPu volumes was found specifically for the sub-group of Nf1(+/-) mice with lower spatial learning performance, suggesting additional evidence for reorganization of this region. We found strong evidence that social and spatial cognition deficits can be associated with PFC/CPu structural changes and reorganization in NF1.
Assuntos
Encéfalo/fisiopatologia , Neurofibromatose 1/fisiopatologia , Animais , Comportamento Animal/fisiologia , Encéfalo/diagnóstico por imagem , Cognição/fisiologia , Transtornos Cognitivos/diagnóstico por imagem , Transtornos Cognitivos/fisiopatologia , Imagem de Tensor de Difusão , Modelos Animais de Doenças , Feminino , Imageamento por Ressonância Magnética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurofibromatose 1/diagnóstico por imagem , Fenótipo , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/fisiopatologia , Comportamento Social , Transtornos do Comportamento Social/fisiopatologia , Relação Estrutura-AtividadeRESUMO
Saccadic behaviour ranges from reflexive (e.g., prosaccade) to goal oriented voluntary movements (e.g., antisaccade). Behavioural asymmetries between vertical and horizontal saccades have been described both in normal individuals (greater delay of vertical prosaccades) and in disease states such as Parkinson's disease (PD) (prosaccades are short and antisaccades are delayed, especially in the vertical plane, possibly due to a frontostriatal deficit). Importantly, the cortical mechanisms for the generation of vertical saccades are largely unknown, both in health and disease, when compared with their horizontal counterpart. Moreover, studies exploring saccadic neural correlates and putative compensatory mechanisms at a functional level in PD are scarce. We investigated horizontal and vertical prosaccades and antisaccades in an eye tracking paradigm in 19 PD patients off medication and 22 healthy controls, followed by a block-design functional Magnetic Resonance Imaging (fMRI) study, consisting of two runs (prosaccade, antisaccade) of 6 blocks each (3 vertical, 3 horizontal). While saccade metrics were not significantly different between groups, PD showed left frontal underactivation during horizontal prosaccades and right parietal overactivation during horizontal and vertical prosaccades and horizontal antisaccades. Moreover, controls showed greater deactivation of the default-mode network (DMN) during antisaccades. Vertical prosaccades were associated with greater right frontal and cerebellar activity in controls, and cuneus hypoactivity in PD. Vertical antisaccades were associated with greater DMN deactivation in both groups and left frontal hypoactivity in PD. Putative functional compensatory changes in the right parietal cortex in PD patients may help to keep saccadic behaviour at the same level as the healthy controls. We provide first time evidence showing that functional cortical asymmetries between vertical and horizontal saccades occur distinctively in PD patients and healthy controls.
Assuntos
Encéfalo/fisiopatologia , Medições dos Movimentos Oculares , Doença de Parkinson/fisiopatologia , Doença de Parkinson/psicologia , Movimentos Sacádicos , Idoso , Mapeamento Encefálico , Feminino , Lobo Frontal/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Vias Neurais/fisiopatologia , Lobo Parietal/fisiopatologia , Desempenho PsicomotorRESUMO
Stroke is one of the leading causes of death and disability worldwide. However, current therapies only reach a small percentage of patients and may cause serious side effects. We propose the therapeutic use of retinoic acid-loaded nanoparticles (RA-NP) to safely and efficiently repair the ischaemic brain by creating a favourable pro-angiogenic environment that enhances neurogenesis and neuronal restitution. Our data showed that RA-NP enhanced endothelial cell proliferation and tubule network formation and protected against ischaemia-induced death. To evaluate the effect of RA-NP on vascular regulation of neural stem cell (NSC) survival and differentiation, endothelial cell-conditioned media (EC-CM) were collected. EC-CM from healthy RA-NP-treated cells reduced NSC death and promoted proliferation while EC-CM from ischaemic RA-NP-treated cells decreased cell death, increased proliferation and neuronal differentiation. In parallel, human endothelial progenitor cells (hEPC), which are part of the endogenous repair response to vascular injury, were collected from ischaemic stroke patients. hEPC treated with RA-NP had significantly higher proliferation, which further highlights the therapeutic potential of this formulation. To conclude, RA-NP protected endothelial cells from ischaemic death and stimulated the release of pro-survival, proliferation-stimulating factors and differentiation cues for NSC. RA-NP were shown to be up to 83-fold more efficient than free RA and to enhance hEPC proliferation. These data serve as a stepping stone to use RA-NP as vasculotrophic and neurogenic agents for vascular disorders and neurodegenerative diseases with compromised vasculature.
Assuntos
Células-Tronco Neurais/efeitos dos fármacos , Células-Tronco Neurais/patologia , Tretinoína/administração & dosagem , Animais , Morte Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Humanos , Isquemia/tratamento farmacológico , Isquemia/patologia , Camundongos , Nanopartículas/administração & dosagem , Nanopartículas/química , Neovascularização Fisiológica/efeitos dos fármacos , Neurogênese/efeitos dos fármacos , Polímeros/química , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/patologiaRESUMO
OBJECTIVES: This work aimed to evaluate the quality of non-sterile formulations compounded at Centro Hospitalar Cova da Beira (Covilhã, Portugal) immediately after preparation and up to the defined 'beyond-use date'. METHODS: Microbiological quality control tests were performed in accordance with monograph 5.1.4 of the European Pharmacopoeia 8.0. Samples of compounded products were collected from January to December 2014 after preparation and were analysed immediately and reanalysed after storage under the established conditions, for each preparation. RESULTS: In the test period, 392 preparations were analysed, corresponding to 24 different formulations (8 intermediate preparations, 11 oral solutions/suspensions and 5 topical preparations). All preparations were in accordance with the pharmacopoeia specifications immediately after preparation. However, for the formulations 'prednisolone oral solution (5â mg/mL)' and 'nitroglycerine and cinchocaine ointment (0.25%/0.5%)', the microbial counts of some batches exceeded the defined limits after storage up to the beyond-use date. CONCLUSIONS: These results show that the compounding practices implemented at this pharmacy department are able to ensure the microbiological quality of compounded products. This microbiological quality control methodology also allowed identification of the need to replace formulations shown not to be stable throughout the storage period. On the basis of these results, a monthly routine of microbiological control of a random sample of compounded medicines was established in order to ensure their quality and safety for use.
RESUMO
Macrophage migration inhibitory factor (MIF) is involved in eosinophil biology and in type 2 inflammation, contributing to allergic and helminthic diseases. We hypothesized that MIF participates in the pathogenesis of eosinophilic esophagitis (EoE), an allergic condition characterized by esophageal eosinophilic inflammation. MIF is highly expressed in esophageal mucosa of patients with EoE, compared with gastro-esophageal reflux disease and control patients, where it co-localizes predominantly with eosinophils. In vitro, recombinant MIF promotes human eosinophil chemotaxis, while MIF antagonist and CXCR4 antagonist, AMD3100, revert this effect. In a model of EoE induced by ovalbumin, Mif-deficient mice have reduced inflammation and collagen deposition compared with wild-type (WT) mice. Importantly, treatment of WT mice with anti-MIF or with AMD3100 during the challenge phase prevents accumulation of eosinophils and tissue remodeling. Conversely, recombinant MIF promoted tissue eosinophil inflammation in allergic mice. Together, these results implicate MIF in the pathogenesis of esophageal inflammation and suggest that targeting MIF might represent a novel therapy for EoE.
Assuntos
Esofagite Eosinofílica/imunologia , Eosinófilos/imunologia , Oxirredutases Intramoleculares/imunologia , Fatores Inibidores da Migração de Macrófagos/imunologia , Adolescente , Adulto , Animais , Benzilaminas , Ciclamos , Esofagite Eosinofílica/genética , Esofagite Eosinofílica/patologia , Esofagite Eosinofílica/terapia , Eosinófilos/patologia , Feminino , Compostos Heterocíclicos/farmacologia , Humanos , Oxirredutases Intramoleculares/genética , Fatores Inibidores da Migração de Macrófagos/genética , Masculino , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Mucosa/imunologia , Mucosa/patologia , Receptores CXCR4/antagonistas & inibidores , Receptores CXCR4/genética , Receptores CXCR4/imunologiaRESUMO
Infection of isolated organs of the reproductive system by Trypanosoma cruzi has been described since Chagas' disease was first studied. A detailed histopathological analysis of mice acutely infected with T. cruzi CL strain showed colonization of male (preputial glands and skin, penis, testicular albuginea, epididymis, vas deferens, seminal vesicles, prostate, coagulative, bulbo urethral and urethral glands) and female (vagina, uterus, oviduct, ovary, mesovary, clitoris and mammary glands) structures of the reproductive system. The results presented herein demonstrated invasion of epithelial cells, pronounced colonization of the epididymis and male genital adnexa, but absence of parasitism in penile corpora cavernosa.
Assuntos
Doença de Chagas/parasitologia , Genitália Feminina/parasitologia , Genitália Masculina/parasitologia , Trypanosoma cruzi/isolamento & purificação , Animais , Feminino , Genitália Feminina/ultraestrutura , Genitália Masculina/ultraestrutura , Masculino , Glândulas Mamárias Animais/parasitologia , Camundongos , Camundongos Endogâmicos BALB C , Microscopia ConfocalRESUMO
Retinal ganglion cells exhibit oscillatory responses which are precisely synchronized over large distances. Here we examined, with multi-electrode recordings, the time course of synchronization during spontaneous and stimulus-driven oscillatory activity. Spontaneous discharges showed synchronized oscillations at approximately 30 Hz, which were occasionally associated with slower superimposed oscillations in the range of 1-5 Hz. Stationary stimuli or moving gratings induced synchronous oscillations at higher frequencies (mean of 79.0 +/- 20.0 Hz for OFF- and 91.7 +/- 11.7 Hz for ON-responses), with time lags of a few milliseconds. At response onset, the first few oscillatory cycles were occasionally time locked to the stimulus. Thereafter, synchronization became independent of stimulus coordination and was exclusively due to neuronal interactions. Oscillatory modulation emerged rapidly and was sustained throughout the responses while oscillation frequency decreased gradually. This periodic patterning of responses persisted despite brief and local occlusion of stimuli, suggesting that synchronous oscillations emerge from population dynamics and entrain cells even if they are intermittently silenced.
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Células Ganglionares da Retina/fisiologia , Potenciais de Ação , Animais , Gatos , Oscilometria , Reconhecimento Visual de Modelos/fisiologia , Fatores de TempoRESUMO
INTRODUCTION: In previous studies, patients with vibroacoustic disease (VAD) presented hyperintense foci in T2 of the cerebral white matter, brainstem and basal nuclei. The most probable etiology is ischemia. One of the most frequent complaints of these patients is balance disturbances which, in two cases, has threatened the patients' ability to maintain their jobs. The purpose of this study was to compare two methods, one neurophysiological (auditory evoked potentials - AEP) and the other structural imaging (brain MRI), in order to determine to what extent the changes detected with these methods may be related to each other in this pathology. METHODS: Twenty individuals occupationally exposed to large pressure amplitude (> or = 90 dB SPL) and low frequency (< or = 500 Hz) noise, received neurological and otorhinolaryngological examinations. All of them had previously received audiograms, tympanograms and electronystagmograms. All 20 patients also received brain MRI and AEP studies. RESULTS: The individuals with vertigo and changes of the AEP present the greater number of changes in the brain MRI. CONCLUSION: This could be an indication that in many VAD cases vertigo may have a central origin.
Assuntos
Potenciais Evocados Auditivos , Imageamento por Ressonância Magnética , Ruído Ocupacional/efeitos adversos , Doenças Profissionais/diagnóstico , Doenças Profissionais/etiologia , Equilíbrio Postural , Transtornos de Sensação/diagnóstico , Transtornos de Sensação/etiologia , Vertigem/diagnóstico , Vertigem/etiologia , Vibração/efeitos adversos , Adulto , Aeronaves , Humanos , Masculino , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Vibroacoustic disease (VAD), is a multisystemic nosological entity, caused by occupational exposure to large pressure amplitude (> or = 90 dB SPL) and low frequency (< or = 500 Hz) (LPALF) noise. The most common neurological finding in patients with VAD is the palmomental reflex (PMR). The aim of this study is to evaluate the frequency and characteristics of this primitive reflex in a population of VAD patients. METHODS: Sixty individuals, occupationally exposed to LPALF noise underwent a neurological examination. In each one, unilateral contraction of the chin muscles was triggered through the stimulation of the thenar eminence. When a response habituation was observed, or when there was no response except previously existing skin retraction and small dimples, an EMG was performed. All these subjects also received brain MRI and measurement of endogenous evoked potentials. RESULTS: Thirty individuals presented unilateral or bilateral PMR; 26 of these presented changes in the brain MRI. EMG measurement evidenced continuous contraction of the chin muscles, without visible PMR, triggered by the stimulation of the thenar eminence. CONCLUSION: PMR is present in 50% of the patients with VAD. In the VAD patients, the frequency of abnormal chin muscle activity is higher than the frequency of PMR and represents a loss of the cortical control over the brainstem structures.