Antioxidative Propolis From Stingless Bees (Heterotrigona Itama) Preserves Endothelium-Dependent Aortic Relaxation of Diabetic Rats: The Role of Nitric Oxide and Cyclic Guanosine Monophosphate

Propolis from stingless bees (Heterotrigona itama) is a resinous compound that exhibits antihyperglycaemia, free radical scavenging, and cardioprotective properties. The effect of propolis on diabetic vessels has not been investigated. Thus, this research aimed to determine the effect of propolis supplementation on the level of antioxidants and its mechanism of action in the aorta of diabetic rats. Male Sprague-Dawley rats were divided into five groups (n=8/group): healthy (control), untreated diabetes (DM), metformin-treated diabetes (DM+M, 300 mg/kg/day metformin), propolis-treated diabetes (DM+P, 300 mg/kg/day propolis extract) and diabetes with combined treatment (DM+M+P, dosage as former). Oral supplementation was conducted for four weeks immediately upon successful induction of diabetes by streptozotocin (60 mg/kg, intraperitoneal injection). At the end of the study, the rats were euthanised, and thoracic aorta was processed into tissue homogenates to determine the levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase-1 (GPx-1) and soluble receptor for advanced glycation end-products (sRAGE). Aorta segments were harvested to examine their relaxation response towards graded concentration of acetylcholine (Ach; 10-8-10-4) M following precontraction with phenylephrine (PE; 10-6 M). Vasorelaxation towards a cumulative dose of propolis (0.01-1.00%) using PE-precontracted healthy aorta (n=6/experiments) was investigated under various simulated conditions: physiological buffer, L-NAME (10-4 M), methylene blue (10-5 M), indomethacin (10-5 M) and elevated glucose (25 mM). Propolis maintained antioxidative enzymes and sRAGE decoy molecules in the aortic tissue of the diabetic rats. The amelioration of diabetes-induced impairment of endothelium-dependent relaxation by propolis was mediated through the nitric oxide(NO)-cyclic guanosine monophosphate (cGMP) pathway. This non-clinical study reports vasoprotective property of propolis in diabetes mellitus.

Importância da educação para prevenção cardiovascular / Importance of education for cardiovascular disease prevention

As doenças cardiovasculares estão entre as maiores causas de morbidade e mortalidade em todo o mundo e são responsáveis por um elevado custo para os sistemas de saúde. Assim, as medidas de prevenção dessas doenças e o controle de seus fatores de risco tornam-se essenciais. Para isso, temos como alternativa, intervenções educacionais para a população, como maneira de fortalecer o indivíduo para realizar as mudanças necessárias em seu estilo de vida, e medidas de educação profissional, para difundir o manejo de emergências cardiovas-culares, com grande impacto na sobrevida de indivíduos com esses problemas. Neste texto, procuramos descrever as medidas educacionais mais frequentes e efetivas para essa prevenção.

Cardiovascular disease is one of the leading causes of morbidity and mortality worldwide and represents a high cost for health systems. Therefore, measures to prevent these conditions and to control their risk factors are essential. One alternative consists of educational interventions for the population as a means of enabling the individual to make the necessary changes in their lifestyle, as well as professional education measures to disseminate the management of cardiovascular emergencies with considerable impact on the survival of individuals with these problems. In this text, we strive to describe the most common and effective educational measures for this prevention

Endothelium as a Potential Target for Treatment of Abdominal Aortic Aneurysm.

Abdominal aortic aneurysm (AAA) was previously ascribed to weaken defective medial arterial/adventitial layers, for example, smooth muscle/fibroblast cells. Therefore, besides surgical repair, medications targeting the medial layer to strengthen the aortic wall are the most feasible treatment strategy for AAA. However, so far, it is unclear whether such drugs have any beneficial effect on AAA prognosis, rate of aneurysm growth, rupture, or survival. Notably, clinical studies have shown that AAA is highly associated with endothelial dysfunction in the aged population. Additionally, animal models of endothelial dysfunction and endothelial nitric oxide synthase (eNOS) uncoupling had a very high rate of AAA formation, indicating there is crucial involvement of the endothelium and a possible pharmacological solution targeting the endothelium in AAA treatment. Endothelial cells have been found to trigger vascular wall remodeling by releasing proteases, or recruiting macrophages along with other neutrophils, into the medial layer. Moreover, inflammation and oxidative stress of the arterial wall were induced by endothelial dysfunction. Interestingly, there is a paradoxical differential correlation between diabetes and aneurysm formation in retinal capillaries and the aorta. Deciphering the significance of such a difference may explain current unsuccessful AAA medications and offer a solution to this treatment challenge. It is now believed that AAA and atherosclerosis are two separate but related diseases, based on their different clinical patterns which have further complicated the puzzle. Therefore, a thorough investigation of the interaction between endothelium and medial/adventitial layer may provide us a better understanding and new perspective on AAA formation, especially after taking into account the importance of endothelium in the development of AAA. Moreover, a novel medication strategy replacing the currently used, but suboptimal treatments for AAA, could be informed with this analysis.

Endothelial damage is aggravated in acute GvHD and could predict its development.

The aim of the present study was to explore whether there is enhanced endothelial dysfunction in patients developing acute GvHD (aGvHD) after allogeneic hematopoietic cell transplantation (allo-HCT) and to identify biomarkers with predictive and/or diagnostic value. In in vitro experiments, endothelial cells (ECs) were exposed to serum from patients with (aGvHD, n=31) and without (NoGvHD, n=13) aGvHD, to evaluate changes in surface adhesion receptors, the reactivity of the extracellular matrix by measuring the presence of Von Willebrand factor (VWF) and platelet adhesion, and the activation of intracellular signaling proteins. Plasma levels of VWF, ADAMTS-13, TNF receptor 1 (TNFR1), soluble vascular cell adhesion molecule 1 and soluble intercellular adhesion molecule 1 were also measured. In vitro results showed a more marked proinflammatory and prothrombotic phenotype in ECs in association with aGvHD. Regarding circulating biomarkers, levels of VWF and TNFR1 above an optimal cutoff score, taken independently or combined, at day 7 after allo-HCT, would be able to positively predict that around 90% of patients will develop aGvHD. Our results demonstrate that endothelial damage is aggravated in those allo-HCT recipients developing aGvHD, and that VWF and TNFR1 are promising predictive aGvHD biomarkers. These findings could contribute to improve the understanding of the pathophysiology of aGvHD.

Disfunción endotelial en el personal naval con obesidad en actividad militar / Endothelial dysfunction in naval personnel in military activity with obesity

Establecer el nivel de disfunción endotelial en el personal naval con obesidad en actividad militar de la Marina de Guerra del Perú, relacionando además el grado de disfunción endotelial con factores modificables (dieta y actividad física), no modificables (antecedentes familiares) y su estratificación cardiovascular. Material y Métodos: La función endotelial fue analizada por doppler vascular donde se evaluó el flujo mediado por dilatación en la arteria braquial, de pacientes con obesidad tipo I, II y III, en reposo, analizando su relación con variables como actividad física, tipo de dieta, antecedentes familiares, edad y género; aplicando parámetros estadísticos (chi-cuadrado y análisis de regresión) con SPSS. Estudio de tipo descriptivo, prospectivo y de corte transversal. Resultados: Se encontró un total de 43.4% de disfunción endotelial en todos los grupos por edades, de los cuales un 49.3% correspondía al sexo masculino. De la totalidad de 173 pacientes, el 56% realizaban ejercicios menos de una hora y recibían dietas mayores de 1800 kcal un total de 113 pacientes encontrándose presencia de disfunción endotelial en el 54% de pacientes de este grupo; el 65% de pacientes con antecedentes familiares presentaron DE, siendo ésta una relación estadísticamente significativa (p<0.05) así como también lo fue para la evaluación de edad, sexo y actividad física; siendo la dieta un parámetro estadísticamente no significativo en el análisis de regresión...

To establish the level of endothelial dysfunction in naval personnel in military activity with obesity of the Navy of Peru, also relating the degree of endothelial dysfunction with modifiable factors (diet and physical activity), unchangeable factors (family history) and cardiovascular stratification. Material and Methods: The endothelial function was analyzed by vascular Doppler, where the flow-mediated dilation in the brachial artery of patients with type I, II and III obesity, at rest was assessed by analyzing its relationship with variables such as physical activity, type of diet, family history, age and gender; applying statistical parameters (chi-square and regression analysis) with SPSS. Descriptive, prospective and cross-sectional study. Results: A total of 43.4% of endothelial dysfunction was found in all age groups, of which 49.3% were male. Of the total 173 patients, 569, performed exercises less than an hour and a total of 113 patients received over 1800kcal diet, endothelial dysfunction was found in 54% of patients in this group; 65% of patients had a positive family history, this being a statistically significant relationship (p <0.05) as well as age, sex and physical activity; diet being not statistically significant in the regression analysis parameter...

Características Imuno-Histoquímicas de Trombos Coronarianos de Pacientes com Infarto do Miocárdio com Elevação de ST e Diabetes Mellitus: Estudo Piloto / Immunohistochemical Characteristics of Coronary Thrombi in Patients with ST-Elevation Myocardial Infarction and Diabetes Mellitus: Pilot Study

Introdução: No contexto do infarto agudo do miocárdio, o diabetes mellitus está associado à maior mortalidade. O objetivo deste estudo foi avaliar se existem, entre os diabéticos, peculiaridades no processo de aterotrombose que poderiam estar implicadas em maior risco para tal desfecho. Métodos: Estudo piloto, proveniente de coorte de pacientes com diagnóstico de infarto agudo do miocárdio com elevação do segmento ST submetidos à intervenção coronária percutânea primária e à tromboaspiração. Foram estudadas variáveis clínico-laboratoriais de cada caso. Os trombos foram analisados quanto às características histopatológicas e às expressões imuno-histoquímicas de CD34, CD61 e fator VIII. Resultados: Foram incluídos os primeiros dez pacientes portadores de diabetes mellitus com material disponível para análise, pareados por idade, sexo e tempo de evolução do infarto com dez pacientes sem diabetes mellitus. Não houve associação significativa entre as expressões imuno-histoquímicas de CD34, CD61 e fator VIII com relação às variáveis histopatológicas, laboratoriais e clínicas estudadas, inclusive com relação à presença de diabetes mellitus. Conclusões: Em análise preliminar, não foi possível demonstrar diferença significativa quanto à expressão da atividade de células endoteliais, da função plaquetária e da ativação da cascata de coagulação entre trombos de pacientes com e sem o diagnóstico de diabetes mellitus submetidos à intervenção coronariana primária...

Background: Diabetes mellitus is associated with increased mortality rates in the setting of acute myocardial infarction. The aim of this study was to evaluate whether there are peculiarities in the atherothrombotic process that might be implicated in increased risk for this outcome in patients with diabetes. Methods: Pilot study in a cohort of patients with ST-elevation acute myocardial infarction undergoing primary percutaneous coronary intervention and aspiration thrombectomy. Clinical and laboratory variables were evaluated in all of the cases. Thrombi were analyzed for histopathological features as well as immunohistochemical expression of CD34, CD61 and factor VIII. Results: Our sample included the first ten diabetic patients with material available for analysis, who were matched according to age, gender and time elapsed since myocardial infarction with ten patients without diabetes. There was no significant association between the immunohistochemical expression of CD34, CD61 and factor VIII with other histopathological, clinical and laboratory variables, including the presence of diabetes mellitus. Conclusions: In this preliminary analysis, it was not possible to demonstrate any significant difference in the expression of endothelial cell activity, platelet function and activation of the coagulation cascade between thrombi of patients with and without diabetes undergoing primary coronary intervention...

Efeitos da filtragem de leucócitos sobre a resposta inflamatória e a função pulmonar de pacientes submetidos à revascularização miocárdica com circulação extracorpórea / Effects of leukocyte filtering on the inflammatory response and pulmonary function in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass

INTRODUÇÃO E OBJETIVOS: A Circulação extracorpórea (CEC) é associada a ativação leucocitária, resposta inflamatória e disfunção pulmonar. Objetivou-se avaliar os efeitos da filtragem leucocitária sobre a resposta inflamatória e a função pulmonar em indivíduos submetidos à revascularização do miocárdio (RM) com CEC. MÉTODO: Após aprovação pelo Comitê de Ética Institucional e obtenção do consentimento informado dos indivíduos, foi realizado estudo prospectivo randomizado, para comparar indivíduos adultos submetidos à RM com CEC, utilizando-se filtragem leucocitária (n=09) ou filtro standard (n=11) durante a CEC. Tomografia computadorizada (CT) de tórax, espirometria, análise da oxigenação e hemograma foram realizados antes da cirurgia. A anestesia foi induzida por via venosa com etomidato (0,3 mg.kg-1), sufentanil (0,3 ug.kg-1), pancurônio (0,08 mg.kg-1) e mantida com isoflurano (0,5 - 1,0 CAM) e sufentanil (0,5 ug.kg-1.h-1). A ventilação mecânica utilizou volume corrente de 8 mL.kg-1, com FiO2 de 0,6 e PEEP de 5 cm H2O, exceto durante a CEC. No grupo Filtragem, durante a CEC, foi inserido um filtro de leucócitos na linha arterial do circuito (LG-6, Pall Biomedical Products) e, no grupo Controle, foi utilizado o filtro Standard. Contagem leucocitária foi realizada após a indução, aos 5, 25 e 50 min de CEC, ao final da cirurgia, com 12 e 24 h PO. Dados hemodinâmicos, PaO2/FiO2, fração de Shunt, interleucinas, elastase e mieloperoxidase foram colhidos antes e após a CEC, no final da cirurgia, com 6,12 e 24 h PO. Trinta minutos depois da indução, e trinta após a CEC, três amostras sequenciais de ar exalado foram colhidas para análise de óxido nítrico (NO), por quimiluminescência. Espirometria e CT de tórax foram realizadas no primeiro dia pós-operatório. Os dados foram analisados por meio de ANOVA de duplo fator para medidas repetidas. RESULTADOS: O tempo de CEC foi similar entre os grupos controle e filtragem (86,78 ± 19,58 versus 104,64 ± 27,76 min, p=0,161)...

BACKGROUND AND OBJECTIVE: The Cardiopulmonary bypass (CPB) is related to leukocyte activation, inflammatory response and lung dysfunction. The aim of this study was to evaluate the effects of CPB-leukocyte filtration on the inflammatory response and lung function after coronary artery bypass grafting (CABG). METHODS: After approval by the institutional ethics committee and informed consent, a prospective randomized study was performed to compare CABG-patients undergoing CPB-leukocyte filtration (n=9) or standard CPB (n=11). Espirometry, chest computed tomography (CT), oxygenation analysis and leukocyte count were performed before surgery. Anesthesia induction was performed intravenously with etomidate (0,3 mg.kg-1), sufentanil (0,3 ug.kg-1), pancuronium bromide (0,08 mg.kg-1) e sustained with isoflurano (0,5 - 1,0 CAM) and sufentanil (0,5 ug.kg-1.h-1). The tidal volume used during mechanical ventilation was 8 mL.kg-1, the FiO2 0.6 and PEEP 5 cm H2O, except during CPB. In Filtered group, during CPB, was inserted a leukocyte filter in the arterial line of CPB circuit (LG-6, Pall Biomedical Products) and, in Control group, the Standard arterial line filter was utilized. Hemodynamic data, PaO2/FiO2, shunt fraction, interleukins, elastase and myeloperoxidase were evaluated before and after CPB, at the end of surgery, and 6, 12 and 24 h PO. Thirty minutes after induction, and Thirty after CPB, three sequential exhaled air samples were collected to perform analysis of nitric oxide (NO), by chemiluminescence technique. Espirometry and chest CT were performed on first PO. Data were analyzed using two-factor ANOVA for repeated measurements. RESULTS: Length of CPB was similar in the filtered and control groups (86.78 ± 19.58 versus 104.64 ± 27.76 min, p = 0.161). The filtered group showed lower neutrophil counts than the control group up to 50 minutes of CPB (3384 ± 2025 versus 6478 ± 3582 U/mm-3, p = 0.036), lower shunt fraction up to 6 hours after surgery (10 ± 2%)...

El consumo de futas y hortalizas ayuda a prevenir el daño endotelial / Consumption of fruits and vegetables in the prevention of endothelial damage

The endothelium helps to maintain the normal structure and homeostasis of the vasculature. However, chronic exposure to cardiovascular (CV) risk factors causes endothelial dysfunction, a phenomenon that is characterized by inflammation, reduced bioavailability of nitric oxide (NO) and a prothrombotic state. Epidemiological studies have shown that regular consumption of fruits and vegetables reduces CV risk, which has caused interest in knowing the bioactive compounds and the mechanisms involved. Among the components that protect the endothelium are antioxidants (vitamin C, vitamin E and poly phenols) and polyunsaturated fatty acids. Vitamin C and E promote vasodilatation protecting NO by blocking the reactive oxygen species (ROS). Poly phenols improve endothelial function primarily by increasing levels of NO, and inhibition of angiogenesis and platelet activation. Diets rich in poly-unsaturated fatty acids have shown beneficial effects by reducing the gene expression of cyclooxygenase-2 and the expression of cell adhesion molecules. This review mainly highlights the current understanding of endothelial dysfunction and the protective effect of endothelial cells by bioactive components of fruits and vegetables.

El endotelio normal ayuda a mantener la estructura y la hemostasia vascular. Sin embargo, la exposición crónica a factores de riesgo cardiovascular (CV) produce disfunción endotelial, fenómeno que se caracteriza por inflamación, disminución en la biodisponibilidad de óxido nítrico (NO) y un estado protrombótico. Estudios epidemiológicos han demostrado que el consumo regular de frutas y hortalizas disminuye el riesgo CV, lo que ha causado interés en conocer los compuestos bioactivos y los mecanismos involucrados. Entre los componentes que protegen el endotelio se encuentran las moléculas antioxidantes (vitamina C, vitamina E y polifenoles) y ácidos grasos poliinsaturados. Las vitaminas C y E favorecen la vasodilatación protegiendo el NO al bloquear las especies reactivas del oxigeno (ROS). Los polifenoles mejoran la función endotelial principalmente por el aumento de los niveles de NO, y la inhibición de la angiogénesis y de la activación plaquetaria. Dietas ricas en ácidos grasos poliinsaturados han mostrado efectos beneficiosos, mediante la reducción de la expresión géni-ca de la ciclooxigenasa-2 y de la expresión de moléculas de adhesión celular. Esta revisión principalmente señala los conocimientos actuales de la disfunción endotelial y el efecto protector de las células endoteliales por componentes bioactivos de frutas y hortalizas.

Características inflamatorias de la obesidad / Inflammatory characteristics of obesity

Currently, obesity is considered a low chronic inflammatory state. The alterations that occur into the expanding adipose tissue parallel the ones seen in a classic inflammatory process. However, the stimulus that triggers inflammation is still unknown. The consequences of the immune system activation are poorly understood. The inflammatory process is not just present at the adipose tissue level. In fact, it can be found in circulation, pancreas, liver and muscle (among other organs). Moreover, inflammation is playing a role on the path physiology of most of cardiovascular risk factors linked to obesity. The aim of this article was to review the current knowledge about this important topic. The understanding of the immune process linked to obesity would allow its clinic study and even the intervention.

Actualmente la obesidad es considerada una enfermedad inflamatoria crónica, de intensidad leve. Las alteraciones que ocurren en el tejido adiposo en expansión son muy similares a las de una inflamación clásica, sin embargo se desconoce aún el agente lesivo que lo gatilla. La activación del sistema inmune no se da solamente en el tejido adiposo, sino que es identificable a nivel circulatorio y en los diferentes órganos relacionados con el metabolismo de sustratos como son hígado, páncreas y músculo. Los antecedentes actuales permiten plantear que tanto la génesis como la evolución de las enfermedades crónicas asociadas a la obesidad tienen un componente inflamatorio. El objetivo de este ensayo es revisar el conocimiento actual sobre el tema. Una cabal comprensión de la activación del sistema inmune en condiciones de exceso nutricional posibilitará su monitorización y eventual intervención.

Células endoteliais circulantes, progenitoras endoteliais e micropartículas / Circulating endothelial cells, endothelial progenitor cells and microparticles

A disfunção endotelial está associada ao desenvolvimento e às complicações da aterosclerose e pode ser um marcador do risco cardiovascular. Em situação fisiológica, ocorre equilíbrio entre a erosão da monocamada de células endoteliais e a capacidade de reposição dessas células para a manutenção da homeostase vascular; porém, quando a perda do endotélio, quer por erosão quer por apoptose, superar a capacidade de reposição celular ou se as células endoteliais não preservarem suas propriedades características, ocorre disfunção endotelial. Biomarcadores de função endotelial prompreendem características das células endotelial que possam ser mensuradas. Entre os novos biomarcadores da função endotelial, um grupo de marcadores do turnover dessas células tem sido proposto: células progenitoras endoteliais, células endoteliais circulantes e micropartículas de diferentes populações celulares, células progenitoras endoteliais, células endoteliais circulantes e micropartículas oferecem um meio não-invasivo para estimar a competência vascular. Níveis de células progenitoras endoteliais podem aumentar em eventos agudos, como o infarto...

Endothelial dysfunction is associated with the development of atherosclerosis complications and may be a marker of cardiovascular risk. In physiological conditions there is a balance between the erosion of the endothelial cell monolayer and the ability of the regenerated endothelium to maintain vascular homeostasis; however, when there is loss of endothelial cells, due to erosion or to apoptosis, surpassing the capacity of endothelial regrowth, or if these cells do not preserve their protective characteristics, the endothelium becomes dysfunctional. Endothelial function biomarkers comprise measurable characteristics of endothelial cells. Among new biomarkers of endothelial function, a group of markers of the turnover of these cells has been proposed: endothelial progenitor cells, circulating endothelial cells, and microparticles of different cell populations. As mediators of endothelial homeostasis, endothelial progenitor cells, circulating endothelial cells and microparticles are non-invasive means to estimate vascular competence. Endothelial progenitor cell levels may increase in acute events, such as in acute myocardial infarction or in vascular injury. However, cardiovascular risk factors reduce the number of endothelial progenitor cells. Microparticles are small fragments released by activated or apoptotic cells (endothelial cells, platelets, etc.) found in healthy individuals and among those with cardiovascular diseases. Platelets are the cells that release the greatest amount of microparticles in the blood, although other cell populations also produce microparticles. Higher levels of endothelial microparticles have been found in acute coronary syndrome, peripheral arterial disease and in patients with cardiovascular risk factors...

Avaliação não-invasiva das propriedades da parede arterial em pacientes com doença de Behçet / Non-invasive evaluation of arterial wall properties in patients with Behçets disease

O envolvimento vascular tem sido reconhecido como uma importante causa de morbidade e mortalidade na Doença de Behçet (DB), mas a importância de métodos não-invasivos em identificar lesões vasculares precoces ainda não foi bem estabelecida. Objetivo: Avaliar as propriedades estruturais e funcionais dos vasos na DB utilizando a medida da velocidade de onda de pulso (VOP) carótido-femoral e a avaliação de carótida pelo echo-tracking system. Métodos: Pacientes com DB sem fatores de risco cardiovasculares tradicionais (hipertensão, diabetes, tabagismo e obesidade) foram selecionados consecutivamente. Todos os pacientes com DB realizaram aferição de VOP e ultrasom de carótida. Pacientes com DB foram divididos de acordo com a presença ou não de envolvimento sistêmico (vascular e/ou ocular e/ou sistema nervoso central) e vascular. Controles saudáveis, pareados para sexo e idade, com os mesmos critérios de exclusão foram selecionados. Resultados: Os vinte e três pacientes com DB (11 homens, média de idade de 35,0±7,6 anos), tiveram níveis significativamente maiores de VOP, comparados ao grupo controle (8,4±1,1 vs. 7,5±1,4 m/s, p=0,017). A espessura íntima-média (594,8±138,6 vs. 561,0±134,2 m, p=0,371), o diâmetro diastólico (6383,7±960,4 vs. 6447,6±1159,7 m, p=0,840), a distensão (401,9±117,7 vs. 337,9±175,3 m, p=0,225) e a distensão relativa (6,2±2,8 vs. 5,4±2,4 m, p=0,293) da artéria carótida foram semelhantes entre os grupos. O grupo com doença sistêmica teve níveis significativamente maiores de VOP (8,7±1,2 vs. 7,8±0,7 m/s, p=0,036) comparado àqueles com manifestação exclusivamente mucocutânea. Pacientes com DB e acometimento vascular tiveram os parâmetros de VOP e echotracking similares aos pacientes sem acometimento vascular, mas apresentaram níveis maiores de colesterol total e LDL (p=0,019 e p=0,012, respectivamente). Uma análise de regressão linear multivariada identificou o nível de triglicerídeos...

Vascular involvement has been recognized as an important cause of morbidity and mortality in Behçets disease (BD) but the role of noninvasive methods in identify early vascular lesions is not established. Objective: To evaluate structural and functional properties of vessels in BD using carotid-femoral pulse wave velocity (PWV) and echo-tracking system. Methods: BD patients without traditional cardiovascular risk factors (hypertension, diabetes, smoking, and obesity) were consecutively selected. All BD patients performed PWV and carotid ultrasound. BD patients were divided according to the presence or not of systemic (vascular and/or ocular and/or central nervous system involvement) and vascular involvement. Healthy controls age- and sex-matched with the same exclusion criteria were selected. Results: The twenty-three BD patients (11 male, mean age 35.0±7.6 years), had a significantly higher PWV levels compared to control group (8.4±1.1 vs. 7.5±1.4 m/s, p=0.017). Intima-media thickness (594.8±138.6 vs. 561.0±134.2 m, p=0.371), diastolic diameter (6383.7±960.4 vs. 6447.6±1159.7 m, p=0.840), distension (401.9±117.7 vs. 337.9±175.3 m, p=0.225), and relative distension (6.2±2.8 vs. 5.4±2.4 m, p=0.293) were similar in both groups. Multivariate linear regression analysis identified triglycerides as the most important factor in increasing PWV levels (p=0.001) in BD. Systemic disease group had significant higher levels of PWV (8.7±1.2 vs. 7.8±0.7 m/s, p=0.036) compared to those with exclusive mucocutaneous manifestations. BD patients with vascular involvement had similar PWV and echo-tracking parameters compared to those without, but had higher total and LDL cholesterol levels (p=0.019 and p=0.012, respectively). CONCLUSIONS: PWV is more useful than carotid ultrasound in detecting...

Avaliação não-invasiva das propriedades da parede arterial em pacientes com doença de Behçet / Non-invasive evaluation of arterial wall properties in patients with Behçets disease

INTRODUÇÃO: O envolvimento vascular tem sido reconhecido como uma importante causa de morbidade e mortalidade na Doença de Behçet (DB), mas a importância de métodos não-invasivos em identificar lesões vasculares precoces ainda não foi bem estabelecida. OBJETIVO: Avaliar as propriedades estruturais e funcionais dos vasos na DB utilizando a medida da velocidade de onda de pulso (VOP) carótido-femoral e a avaliação de carótida pelo echo-tracking system. MÉTODOS: Pacientes com DB sem fatores de risco cardiovasculares tradicionais (hipertensão, diabetes, tabagismo e obesidade) foram selecionados consecutivamente. Todos os pacientes com DB realizaram aferição de VOP e ultrasom de carótida. Pacientes com DB foram divididos de acordo com a presença ou não de envolvimento sistêmico (vascular e/ou ocular e/ou sistema nervoso central) e vascular. Controles saudáveis, pareados para sexo e idade, com os mesmos critérios de exclusão foram selecionados. RESULTADOS: Os vinte e três pacientes com DB (11 homens, média de idade de 35,0±7,6 anos), tiveram níveis significativamente maiores de VOP, comparados ao grupo controle (8,4±1,1 vs. 7,5±1,4 m/s, p=0,017). A espessura íntima-média (594,8±138,6 vs. 561,0±134,2 m, p=0,371), o diâmetro diastólico (6383,7±960,4 vs. 6447,6±1159,7 m, p=0,840), a distensão (401,9±117,7 vs. 337,9±175,3 m, p=0,225) e a distensão relativa (6,2±2,8 vs. 5,4±2,4 m, p=0,293) da artéria carótida foram semelhantes entre os grupos. O grupo com doença sistêmica teve níveis significativamente maiores de VOP (8,7±1,2 vs. 7,8±0,7 m/s, p=0,036) comparado àqueles com manifestação exclusivamente mucocutânea. Pacientes com DB e acometimento vascular tiveram os parâmetros de VOP e echotracking similares aos pacientes sem acometimento vascular, mas apresentaram níveis maiores de colesterol total e LDL (p=0,019 e p=0,012, respectivamente). Uma análise de regressão linear multivariada identificou o nível de triglicerídeos...

INTRODUCTION: Vascular involvement has been recognized as an important cause of morbidity and mortality in Behçets disease (BD) but the role of noninvasive methods in identify early vascular lesions is not established. OBJECTIVE: To evaluate structural and functional properties of vessels in BD using carotid-femoral pulse wave velocity (PWV) and echo-tracking system. METHODS: BD patients without traditional cardiovascular risk factors (hypertension, diabetes, smoking, and obesity) were consecutively selected. All BD patients performed PWV and carotid ultrasound. BD patients were divided according to the presence or not of systemic (vascular and/or ocular and/or central nervous system involvement) and vascular involvement. Healthy controls age- and sex-matched with the same exclusion criteria were selected. RESULTS: The twenty-three BD patients (11 male, mean age 35.0±7.6 years), had a significantly higher PWV levels compared to control group (8.4±1.1 vs. 7.5±1.4 m/s, p=0.017). Intima-media thickness (594.8±138.6 vs. 561.0±134.2 m, p=0.371), diastolic diameter (6383.7±960.4 vs. 6447.6±1159.7 m, p=0.840), distension (401.9±117.7 vs. 337.9±175.3 m, p=0.225), and relative distension (6.2±2.8 vs. 5.4±2.4 m, p=0.293) were similar in both groups. Multivariate linear regression analysis identified triglycerides as the most important factor in increasing PWV levels (p=0.001) in BD. Systemic disease group had significant higher levels of PWV (8.7±1.2 vs. 7.8±0.7 m/s, p=0.036) compared to those with exclusive mucocutaneous manifestations. BD patients with vascular involvement had similar PWV and echo-tracking parameters compared to those without, but had higher total and LDL cholesterol levels (p=0.019 and p=0.012, respectively). CONCLUSIONS: PWV is more useful than carotid ultrasound in detecting...

Dilatação fluxo-mediada da artéria braquial: estudo da função endotelial em mulheres na menopausa / Flow-mediated dilatation of the brachial artery. Study of the endotelial function in menopause women

Introdução: O risco de doença cardiovascular aumenta após a menopausa. A diminuição dos níveis de estrogênio altera a função endotelial, o primeiro evento no processo da aterosclerose. A função endotelial pode ser avaliada pela dilatação fluxo-mediada da artéria braquial (DILA), durante a hiperemia reativa. Objetivo: Em nosso estudo, comparamos as diferenças da DILA em mulheres no menácme e na menopausa. Métodos: Foram avaliadas 35 mulheres no menácme (grupo controle) e 38 na menopausa. A idade média das mulheres no grupo controle foi de 34,08 anos (20 a 49 anos) e, no grupo menopausa, 56,92 mais ou menos 7,41 anos (36 a 70 anos). Nenhuma das mulheres do grupo menopausa estavam em terapia estrogênica e 16 faziam uso de fitohormônio. O DILA foi medido na artéria braquial, 5 cm acima da prega cubital, utilizado transdutor linear de 14MHz. As imagens no modo B para a medida do diâmetro da artéria braquial foram selecionadas na fase diastólica do fluxo de onda. As medidas do diâmetro da artéria eram avaliadas antes, e 60 segundos após 5 minutos de oclusão da artéria braquial com manguito pneumático....

Borate transporter SLC4A11 mutations cause both Harboyan syndrome and non-syndromic corneal endothelial dystrophy.

Harboyan syndrome, or corneal dystrophy and perceptive deafness (CDPD), consists of congenital corneal endothelial dystrophy and progressive perceptive deafness, and is transmitted as an autosomal recessive trait. CDPD and autosomal recessive, non-syndromic congenital hereditary endothelial corneal dystrophy (CHED2) both map at overlapping loci at 20p13, and mutations of SLC4A11 were reported recently in CHED2. A genotype study on six families with CDPD and on one family with either CHED or CDPD, from various ethnic backgrounds (in the seventh family, hearing loss could not be assessed because of the proband's young age), is reported here. Novel SLC4A11 mutations were found in all patients. Why some mutations cause hearing loss in addition to corneal dystrophy is presently unclear. These findings extend the implication of the SLC4A11 borate transporter beyond corneal dystrophy to perceptive deafness.

Inflamación y disfunción del endotelio / Inflammation and endothelial dysfunction

La disfunción endotelial es una patología que antecede a las patologías de origen vascular. La disfunción endotelial se ha definido como una reducción en la respuesta vasodilatadora dependiente del endotelio y del sistema del oxido nítrico (NO). Los mecanismos causantes de la disfunción endotelial no están totalmente definidos y en este artículo se hace una revisión de las más estudiadas. En este sentido, es conocido que cuando existe disfunción endotelial se favorece la activación de las plaquetas facilitándose la formación de trombos. Pero también las plaquetas podrían participar directamente en la génesis y progresión de la disfunción endotelial

Endothelial dysfunction is a pathology that appears early before any morphological vascular alteration could be detected. Endothelial dysfunction has been defined as a reduction in the endothelium and nitric oxide (NO)- dependente vasorelaxation response. The mechanisms involved in the genesis and development of endothelial dysfunction have not defined at all. In the present work, we have reviewer same of the main studied mechanisms associated with endothelial dysfunction. In this regard, it is well known that the existence of endothelial dysfunction provoked the activation of platelets although less is known if platelets by themselves could be also involved in the genesis and progression of endothelial dysfunction

Abnormal blood vessel development in mice lacking presenilin-1.

Presenilin-1 (PS1) is a gene responsible for the development of early-onset familial Alzheimer's disease. To explore the potential roles of PS1 in vascular development, we examined the vascular system of mouse embryos lacking PS1. PS1-deficient embryos exhibited cerebral hemorrhages and subcutaneous edema by mid gestation. Immunohistochemical analysis revealed vascular remodeling failure in the stomach and trunk dorsal median region of the skin and insufficient formation of the perineural plexus around the spinal cord of the PS1 mutant embryos. The number of capillary sprouting sites reduced and the capillary diameter increased in the mutant brains, especially at the amygdaloid and striatal regions. Endothelial cells in the sprouting capillaries of the mutant mice showed abnormal morphologies such as multiplication, apoptotic and necrotic images, in contrast to pericytes showing a normal appearance. An in vitro assay using para-aortic splanchnopleural mesoderm (P-Sp) revealed aberrant angiogenesis in the explant culture from the mutant. These findings suggest the essential roles of PS1 in angiogenesis.

Endothelium dysfunction in LDL receptor knockout mice: a role for H2O2.

1. In this study, the role of endogenous H(2)O(2) as an endothelium-dependent relaxant factor was characterised in aortas from C57BL/6J and LDL receptor-deficient mice (LDLR(-/-)). 2. Aortic rings from LDLR(-/-) mice showed impaired endothelium-dependent relaxation to acetylcholine (ACh; 0.001-100 micro M) and to the Ca(2+) ionophore A23187 (0.001-3 micro M) compared with aortic rings from control mice. Endothelium-independent relaxation produced by the NO donor, 3-morpholino-sydnonimine (SIN-1) was not different between strains. 3. Pretreatment of vessels with L-NNA (100 micro M) or L-NNA (100 micro M) plus L-NAME (300 micro M) plus haemoglobin (10 micro M) markedly decreased, but did not abolish the relaxation to ACh in control mice. In the aortas from LDLR(-/-) mice treated with L-NNA (100 micro M), ACh induced a contractile effect. Catalase (800 and 2400 U ml(-1)) shifted to the right the endothelium-dependent relaxation to ACh in aortas from control but not from LDLR(-/-) mice. Aminotriazole (50 mM), which inhibits catalase, abolished its effect on control mice. Treatment of vessels with L-NNA and catalase abolished vasorelaxation induced by ACh. Indomethacin (10 micro M) did not modify the concentration-response curve to ACh. Superoxide dismutase (300 U ml(-1)) did not change ACh-induced relaxation in both strains. 4. Exogenous H(2)O(2) produced a concentration-dependent relaxation in endothelium-denuded aortic rings, which was not different between strains. 5. It is concluded that H(2)O(2) greatly contributes to relaxation to ACh in aorta from control mice. Endothelial-dependent relaxation to ACh is impaired in LDLR(-/-) mice. Reduced biosynthesis or increased inactivation of H(2)O(2) is the possible mechanism responsible for endothelial dysfunction in aortas of atherosclerosis-susceptible LDLR(-/-) mice.