RESUMO
Tauopathies are a group of neurodegenerative diseases characterized by the alteration/aggregation of TAU protein, for which there is still no effective treatment. Therefore, new pharmacological targets are being sought, such as elements of the endocannabinoid system (ECS). We analysed the occurrence of changes in the ECS in tauopathies and their implication in the pathogenesis. By integrating gene expression analysis, immunofluorescence, genetic and adeno-associated virus expressing TAU mouse models, we found a TAU-dependent increase in CB2 receptor expression in hippocampal neurons, that occurs as an early event in the pathology and was maintained until late stages. These changes were accompanied by alterations in the endocannabinoid metabolism. Remarkably, CB2 ablation in mice protects from neurodegeneration induced by hTAUP301L overexpression, corroborated at the level of cognitive behaviour, synaptic plasticity, and aggregates of insoluble TAU. At the level of neuroinflammation, the absence of CB2 did not produce significant changes in concordance with a possible neuronal location rather than its classic glial expression in these models. These findings were corroborated in post-mortem samples of patients with Alzheimer's disease, the most common tauopathy. Our results show that neurons with accumulated TAU induce the expression of the CB2 receptor, which enhances neurodegeneration. These results are important for our understanding of disease mechanisms, providing a novel therapeutic strategy to be investigated in tauopathies.
Assuntos
Encéfalo/metabolismo , Neuroproteção/fisiologia , Receptor CB2 de Canabinoide/biossíntese , Tauopatias/metabolismo , Proteínas tau/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Animais , Encéfalo/patologia , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Pessoa de Meia-Idade , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologia , Receptor CB2 de Canabinoide/genética , Tauopatias/genética , Tauopatias/patologia , Proteínas tau/genéticaRESUMO
BACKGROUND AND AIMS: In Spain, the incidence of coronary heart disease is below that expected based on the burden of classic cardiovascular risk factors present in the population. Whether the risk associated with metabolic syndrome is lower in Spain deserves to be investigated. This study evaluates the association of incident clinical coronary heart disease with metabolic syndrome and each of its individual defining components in a sample of Spanish working males. METHODS AND RESULTS: Among the workers of a factory (MESYAS registry), 208 incident cases of coronary heart disease (between 1981 and 2005) were age-matched with 2080 healthy workers visited in 2004-2005. Metabolic syndrome was characterized using modified criteria of the joint consensus definition (2009). Metabolic syndrome was strongly associated with coronary heart disease (OR = 4.03; 95% CI: 2.98, 5.45) and the risk seemed to be fully explained by metabolic syndrome components (OR = 0.84, p = 0.54 after adjustment). Odds ratios for the independent effects of the diagnostic criteria were: hypertriglyceridemia (OR = 3.39, p < 0.001), hyperglycemia (OR = 2.70, p < 0.001), low HDL cholesterol (OR = 2.35, p < 0.001), hypertension (OR = 1.49, p = 0.016) and overweight (OR = 1.07, p = 0.678). Young workers showed a higher risk associated with metabolic syndrome. CONCLUSION: The risk associated with metabolic syndrome is fully explained by its components considered independently. The risk of coronary heart disease in a Spanish male working population is considerably increased among those with metabolic syndrome, by a factor similar to that described for other countries. Public health measures to prevent a rise in the prevalence of metabolic syndrome are advisable to minimize cardiovascular disease rate in Spain.
Assuntos
Doença das Coronárias/epidemiologia , Síndrome Metabólica/epidemiologia , População Branca , Adulto , Idoso , Estudos de Casos e Controles , Doença das Coronárias/complicações , Doença das Coronárias/prevenção & controle , Humanos , Hiperglicemia/complicações , Hiperglicemia/fisiopatologia , Hipertensão/complicações , Hipertensão/fisiopatologia , Hipertrigliceridemia/complicações , Hipertrigliceridemia/fisiopatologia , Modelos Logísticos , Masculino , Síndrome Metabólica/complicações , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Sobrepeso/complicações , Sobrepeso/fisiopatologia , Prevalência , Medição de Risco , Fatores de Risco , Espanha/epidemiologia , Adulto JovemRESUMO
The mass transfer phenomenon occurs in many operations of the food industry with the purpose of obtaining a given substance of interest, removing water from foods, or introducing a given substance into the food matrix. Pretreatments that modify the permeability of the cell membranes, such as grinding, heating, or enzymatic treatment, enhance the mass transfer. However, these techniques may require a significant amount of energy and can cause losses of valuable food compounds. Pulsed electric field (PEF) technology is a nonthermal processing method that causes permeabilization of cell membranes using low energy requirements and minimizing quality deterioration of the food compounds. Many practical applications of PEF for enhancing mass transfer in the food industry have been investigated. The purpose of this chapter is to give an overview of the state of the art of application of PEF for improving mass transfer in the food industry.
Assuntos
Técnicas Eletroquímicas , Manipulação de Alimentos/métodos , Permeabilidade da Membrana Celular , Eletroporação , Aditivos Alimentares/química , Manipulação de Alimentos/economia , Alimentos em Conserva/efeitos adversos , Alimentos em Conserva/análise , Alimentos em Conserva/economia , Óleos de Plantas/análise , Óleos de Plantas/economia , Vinho/análise , Vinho/economiaRESUMO
We present the Spanish adaptation made by the CEIPC of the European Guidelines on Cardiovascular Disease Prevention (CVD) in Clinical Practice 2008. This guide recommends the SCORE model for risk evaluation. The aim is to prevent premature mortality and morbidity due to CVD through the management of its related risk factors in clinical practice. The guide focuses on primary prevention and emphasizes the role of the nurses and primary care medical doctors in promoting a healthy life style, based on increasing physical activity, change dietary habits, and non smoking. The therapeutic goal is to achieve a Blood Pressure < 140/90 mmHg, but among patients with diabetes, chronic kidney disease, or definite CVD, the objective is <130/80 mmHg. Serum cholesterol should be < 200 mg/dl and cLDL<130 mg/dl, although among patients with CVD or diabetes, the objective is <100 mg/dl (80 mg/dl if feasible in very high-risk patients). Patients with type 2 diabetes and those with metabolic syndrome must lose weight and increase their physical activity, and drugs must be administered whenever applicable, to reach body mass index (BMI) guided and waist circumference objectives. In diabetic type 2 patients, the objective is glycated haemoglobin <7%. Allowing people to know the guides and developing implementation programs, identifying barriers and seeking solutions for them, are priorities for the CEIPC in order to transfer the recommendations established into the daily clinical practice.
Assuntos
Doenças Cardiovasculares/prevenção & controle , Medicina Clínica/normas , Fatores Etários , Biomarcadores , Pressão Sanguínea , Índice de Massa Corporal , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/terapia , Colesterol/sangue , Ensaios Clínicos como Assunto , Diabetes Mellitus Tipo 2/prevenção & controle , Humanos , Estilo de Vida , Inibidores da Agregação Plaquetária/uso terapêutico , Padrões de Prática Médica , Fatores de Risco , EspanhaRESUMO
The present CEIPC Spanish adaptation of the European Guidelines on Cardiovascular Disease Prevention in Clinical Practice 2008. This guide recommends the SCORE model for risk evaluation. The aim is to prevent premature mortality and morbidity due to CVD by means of dealing with its related risk factors in clinical practice. The guide focuses on primary prevention and emphasizes the role of the nurses and primary care doctors in promoting a healthy life style, based on increasing physical activity, changing dietary habits, and not smoking. The therapeutic goal is to achieve a Blood Pressure < 140/90 mmHg, but in patients with diabetes, chronic kidney disease, or definite CVD, the objective is < 130/80 mmHg. Serum cholesterol should be < 200 mg/dl and cLDL < 130 mg/dl, although in patients with CVD or diabetes, the objective is < 100 mg/dl (80 mg/dl if feasible in very high-risk patients). Patients with type 2 diabetes and those with metabolic syndrome must lose weight and increase their physical activity, and drugs must be administered whenever applicable, with the objective guided by body mass index and waist circumference. In diabetic type 2 patients, the objective is glycated haemoglobin < 7%. Allowing people to know the guides and developing implementation programs, identifying barriers and seeking solutions for them, are priorities for the CEIPC in order to put the recommendations into practice.
Assuntos
Doenças Cardiovasculares/prevenção & controle , Comportamento , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/psicologia , Doenças Cardiovasculares/terapia , Humanos , Hipertensão/complicações , Hipertensão/terapia , Fatores de Risco , Fatores Socioeconômicos , EspanhaRESUMO
The term primitive neuroectodermal tumor (PNET) should be included in the differential diagnosis of small round blue cell tumors, which come from the neural crest and explain their neuroectodermal character. This is one of the most indifferentiated histological types of malignant tumors. In the PNET family, we high light the Ewing's Sarcoma, that is frecuently located in bony sites and has a less frequent localization in soft tissues. We focus on one atypic case of PNET/Extraosseus Ewing's Sarcoma that involves the external auditory canal and infiltrates the temporal bone. Surgery followed by postoperative chemotherapy and radiation offers the best local control of the disease.
Assuntos
Neoplasias Ósseas/patologia , Tumores Neuroectodérmicos Primitivos/patologia , Sarcoma de Ewing/patologia , Osso Temporal/patologia , Adulto , Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/cirurgia , Terapia Combinada , Humanos , Imageamento por Ressonância Magnética , Masculino , Tumores Neuroectodérmicos Primitivos/radioterapia , Tumores Neuroectodérmicos Primitivos/cirurgia , Sarcoma de Ewing/radioterapia , Sarcoma de Ewing/cirurgia , Osso Temporal/efeitos da radiação , Osso Temporal/cirurgiaRESUMO
Most exercise testing is performed in adults with known or suspected ischemic heart disease. In the last few years cardiac imaging techniques have been applied in this field, improving the information obtained with the procedure. However, the exceptions to this rule are emerging rapidly not only in healthy people (asymptomatic individuals, athletes, handicapped people) but also in cardiac patients (advanced congestive heart failure, hypertension, rhythm disorders, congenital heart disease, etc.). All the-se issues justify the need for a multidisciplinary consensus document in Spain. This paper reviews and updates the methodological aspects of the stress test, including those related to oxygen consumption measurements. The main aim of this review was to determine the role of exercise testing in the evaluation of ischemic heart disease as well as the applications of imaging stress testing. The usefulness of this test in other non-ischemic cardiac disorders and in selected subsets of healthy people is also reviewed.
Assuntos
Teste de Esforço/normas , Isquemia Miocárdica/diagnóstico , Adulto , Humanos , Sociedades Médicas , EspanhaAssuntos
Hemorragia Cerebral/etiologia , Infarto Cerebral/etiologia , Trombose Intracraniana/complicações , Trombose Intracraniana/etiologia , Cirrose Hepática/complicações , Lobo Temporal/irrigação sanguínea , Adulto , Hemorragia Cerebral/patologia , Hepatite B/complicações , Humanos , Trombose Intracraniana/patologia , Cirrose Hepática/virologia , Imageamento por Ressonância Magnética , Masculino , Lobo Temporal/patologiaRESUMO
If blood for monitoring of heparin therapy is collected through indwelling catheters it may be contaminated by exogenous heparin. A prospective study comparing thrombin times in plasma obtained by venipuncture and by collection through heparin perfused catheters showed that 26 out of 77 catheter samples were contaminated. In 16 of these 26 cases, overestimation of the heparin effect would have led to incorrect dosage recommendations. It is concluded that blood for laboratory monitoring of heparin treatment should be collected by venipuncture.