Relação entre biomarcadores inflamatórios, de adesão celular, de estresse oxidativo, de lesão endotelial, remodelamento tecidual e vascular e os diferentes estágios da doença venosa crônica primária (classes clínicas CEAP C0a, C2, C3, C4) / Relationship between biomarkers of inflammation, cell adhesion, oxidative stress, endothelial cell damage, vascular and tissue remodeling and the different stages of primary chronic venous disease (CEAP clinical classes C0a, C2, C3, C4)

A doença venosa crônica (DVC) é uma desordem complexa que compreende sinais e sintomas que variam das telangiectasias às úlceras ativas. A DVC é classificada de acordo com aspectos clínicos, etiológicos, anatômicos e fisiopatológicos (CEAP) em sete classes variando de C0 à C6. A principal causa da DVC é a hipertensão venosa que altera o fluxo venoso e, consequentemente, a força de cisalhamento que induz alterações fenotípicas nas células endoteliais que passam a expressar mediadores pró-inflamatórios e pró-trombóticos, que levam à adesão de leucócitos, ao aumento do estresse oxidativo, da permeabilidade vascular e do dano endotelial e ao remodelamento tecidual e vascular.Em virtude dos inúmeros mecanismos e da diversidade de moléculas envolvidas na patogênese e progressão da DVC, é essencial conhecer a interação entre elas e também saber quais são as moléculas (biomarcadores) que se correlacionam positivamente ou negativamente com a gravidade da doença. Foram avaliados os níveis de Interleucina-6 (IL-6), sL-selectina, sE-selectina, sP-selectina, molécula de adesão intercelular-1solúvel (sICAM-1), molécula de adesão das células vasculares-1 solúvel (sVCAM-1), ativador tecidual do plasminogênio (tPA), atividade do inibidor do ativador do plasminogênio-1 (PAI-1), trombomodulina solúvel (sTM), fator de von Willebrand (vWF), metaloproteinase de matriz (MMP)-2, MMP-3, MMP-9, inibidor tecidual das MMPs -1 (TIMP-1), angiopoietina-1 e -2, sTie-2 e s-Endoglina e fator de crescimento do endotélio vascular (VEGF) no sangue coletado da veia braquial de 173 mulheres com DVC primária divididas em grupos C2, C3, C4 e C4 menopausadas (C4m) e de 18 voluntárias saudáveis (grupo C0a). Foram também analisados os níveis urinários de ent-prostaglandina F2α nesses grupos. Não foram encontradas diferenças estatisticamente significativas com relação às concentrações sanguíneas e urinárias de sE-selectina, sP-selectina, sICAM-1, atividade de PAI-1, MMP-3, razão TIMP-1/MMP-3 ...

Chronic Venous Disease (CVD) is a complex disorder, which encompasses signs and symptoms that vary from telangiectasias to active ulcers. The CVD is classified according Clinical, Etiologic, Anatomical and Pathophysiological (CEAP) aspects into seven classes varying from C0 to C6. The main cause of CVD is venous hypertension, which alters venous flow and consequently, shear stress. Abnormal shear stress induces phenotypic changes in endothelial cells that start to express pro-inflammatory and pro-thrombotic mediators that lead to leukocyte adhesion, oxidative stress, increased vascular permeability and endothelial cell damage and tissue and vascular remodeling. Due to several mechanisms and the diversity of molecules involved in the pathogenesis and progression of CVD, is essential to know the interplay between them and which are the molecules (biomarkers) that correlate positively and negatively with the severity of the disease. We investigated the levels of interleukin-6 (IL-6), sL-selectin, sE-selectin, sP-selectin, soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1) activity, soluble thrombomodulin (sTM), von Willebrand factor (vWf), matrix metalloproteinase (MMP)-2, MMP-3, MMP-9, tissue inhibitor of metaloproteinases-1 (TIMP-1), angiopoietin-1 and -2, sTie-2, s-Endoglin, vascular endothelial growth factor (VEGF) in the blood taken from the brachial vein of 173 patients with primary CVD divided into C2, C3, C4 and menopaused C4 (C4m) groups and 18 healthy volunteers (C0a group).We also investigated the urinary levels of ent-prostaglandin F2α in these groups. There was no statistically significant difference between groups with respect to blood or urinary levels of sE-selectin, sP-selectin, sICAM-1, PAI-1 activity, MMP-3, TIMP-1/MMP-3 ratio, angiopoietin-2, angiopoietin-1/angiopoietin-2 ratio, s-Endoglin ...

Dilatação Fluxo-Mediada da artéria braquial como método de avaliação da função endotelial na pré-eclâmpsia e em gestantes normotensas / Flow-mediated dilation of the brachial artery as a method of evaluating endothelial function in preeclampsia and in normotensive pregnant women

Introdução: durante as últimas duas décadas, a ativação de células endoteliais tornou-se o evento mais estudado na compreensão da fisiopatologia da pré-eclâmpsia (PE).Acredita-se que fatores desconhecidos, provavelmente de origem placentária, são secretados na circulação materna, provocando ativação e lesão endotelial. A dilatação fluxo mediada (DILA) da artéria braquial é técnica não invasiva, capaz de avaliar a integridade endotelial. Objetivos: este estudo avalia o índice de dilatação da artéria braquial medido pelo DILA em portadoras de PE, comparativamente a gestantes normotensas.Materiais e métodos: foram estudadas 78 gestantes atendidas na Maternidade do Hospital das Clínicas da UFMG, sendo 51 delas com diagnóstico de PE e 27 normotensas. Adilatação fluxo-mediada da artéria braquial foi obtida de acordo com a técnica descrita por Anderson e Mark, em 1989, modificada. Resultados: a dilatação fluxo-mediada da artéria braquial mostrou-se significativamente reduzida nas gestantes portadoras de pré-eclâmpsia em relação às normotensas (6,098±5,633; 15,48±8,56; p menor que 0,01). Conclusões: pacientes em pré-eclâmpsia possuem DILA significativamente alterado quando comparadas às gestantes normais, sugerindo que tenham lesão endotelial.

Introduction: activation of endothelial cells became the most studied event in understanding the pathophysiology of preeclampsia (PE) during the past two decades. Unknown factors, probably of placental origin, are secreted into the maternal blood flow, causing activation and endothelial damage. Flow-mediated dilation (FMD) of the brachial artery is a noninvasive technique able to evaluate endothelial integrity. Objectives: this study evaluates the rate of the brachial artery dilatation measured by FMD in women with PE compared to normotensive pregnant women. Materials and methods: a total of 78pregnant women seen at the University Hospital from Minas Gerais were studied. From the total, 51 were diagnosed with PE diagnostic and 27 were normotensive. The flow-mediated dilation of the brachial artery was obtained according to the technique described by Anderson and Mark in 1989, adapted. Results: Flow-mediated dilation of the brachial artery was significantly reduced in pregnant women with preeclampsia when compared to the normotensive patients (6.098 ± 5.633, 15.48 ± 8.56, p less than 0.01). Conclusion: patients in preeclampsia have significantly altered FMD when compared to the normal pregnancies, suggesting endothelial lesion.

Interleucina-6, moléculas de adesão intercelular-1 e microalbuminúria na avaliação da lesão endotelial: revisão de literatura / Interleukin-6, intercellular-1 adhesion molecules and microalbuminuria in the evaluation of endothelial injury: review of the literature

É importante que o profissional médico desenvolva uma boa avaliação crítica sobre a utilização de procedimentos voltados à detecção, seguimento e prevenção de estados patológicos. Com essa finalidade, imuneros marcadores de lesão endotelial têm sido pesquisado e suas análise parecem produzir orientações úteis que melhoram a eficácia do tratamento, otimizando resultados e favorecendo o custo global dos cuidados à saúde. Esta revisão tem por objetivo avaliar a importância da interleucina-6 e das moléculas de adesão intercelular-1, marcadores inflamatórios participantes da fisiopatologia da doença aterosclerótica e que são tradicionalmente menos utilizados na investigação clínica dessa afecção. Foram investigados o comportamento e perfil desses marcadores...

Aspectos atuais da fisiopatologia da pré-eclâmpsia com repercussões na conduta / Current aspects in the pathophysiology of preeclampsia with repercussions in the management

A pré-eclâmpsia é a principal causa de morte materna nos países em desenvolvimento e contribui para a prematuridade e outras complicações perinatais. Sua etiologia ainda é desconhecida e exitem diversas formulações fisiopatológicas que se aplicam à doença. Um dos pontos centrais da fisiopatologia da doença é a lesão endotelial generalizada. Esse evento vem sendo estudado no Centro de Medicina Fetal da Universidade Federal de Minas Gerais, e diversos marcadores de lesão endotelial já foram descobertos e correlacionados com a ocorrência da pré-eclâmpsia. A literatura clássica e estudos realizados neste centro indicam e confirmam a teoria da placentação secundária deficiente, como causa da lesão endotelial dos vasos placentários. Uma exacerbação do sistema renina-angiotensina seria responsável pelo acometimento generalizado do organismo materno. Um método promissor para se verificar essa lesão endotelial generalizada é a dilatação fluxo-mediada da artéria braquial. É assumida a lesão endotelial como ponto central da fisiopatologia da doença; então, estão em andamento diversos estudos para se avaliar tratamentos que recuperem o endotélio e ofereçam sua proteção.

Preeclampsia is the main cause of maternal mortality in developing countries and it contributes to pre-term birth and other perinatal complications. Its etiology is still unknown and there are lots of physiopathology formulations that apply to this disease. One of the central points of this disease's physiopathology is the systemic endothelial lesion. This event has been studied in the Fetal Medicine Center of Universidade Federal de Minas Gerais and a great number of markers of endothelial lesion has been discovered, and correlated with the presence of preeclampsia. Classic literature and other studies, performed by our center, point out and confirm the theory of the deficient secondary placentation as cause of endothelial lesion in placentary vessels. An uncontrolled activity of the renin-angiotensin system would be responsible for the systemic compromise of the maternal organism. A promising method to verify this systemic endothelial lesion is the flow-mediated dilation of the brachial artery. It is assumed the endothelial lesion as the central point of this disease's physiopathology; thus, there are several studies to evaluate treatments which provide recovery and protection to the vascular endothelium.

Análise do efeito imediato do jato de CO2 sobre o endotélio vascular de caprinos / Analysis of the immediate effect of CO2 jet on the vascular endothelium of caprines

O objetivo deste estudo foi avaliar a influência do jato de CO2 na parede da Artéria Torácica Interna Esquerda (ATIE) e Artéria Interventricular Anterior (AIVA), simultaneamente, em um modelo experimental em caprinos, comparando os efeitos imediatos do uso do CO2 com fluxo de 5 L/min e 10 L/min, por 20 minutos, intermitente (30 em 30 segundos), com e sem umidificação. Utilizou-se a Reação de Imunoperoxidase para marcação do endotélio e a mensuração foi feita pelo Quantimet, seguindo a escala de IP para lesão vascular. Verificou-se que a lesão endotelial é fluxo dependente, sendo maior com jato de CO2 com fluxo de 10 L/min e menor com 5 L/min. A umidificação reduziu a lesão endotelial com fluxo de 5 L/min, não alterando com fluxo de 10 L/min. As artérias envolvidas na anastomose (ATIE e AIVA) são afetadas simultaneamente, sendo que a agressão é maior para AIVA / The objective of this study was to assess the effect of CO2 jet on the wall of the Left Internal Thoracic Artery (LITA) and the Anterior Interventricular Artery (AIVA) simultaneously in an experimental model in caprines comparing the immediate effects of the use of CO2 with flow rate of 5 L/min and 10 L/min, during 20 minutes, intermittently (every 30 seconds) with and without humidification. Immunoperoxidase reaction was utilized to mark the endothelium and the measurement was made by means of Quantimet, following IP scale for vascular lesion. It was revealed that the endothelial lesion is flow-dependent, being larger eith CO2 jet with 10 L/min and smaller with flow rate of 5 L/min, not changing with flow rate of 10 L/min. The arteries involved in anastomosis (LITA and AIVA) are affected simultaneously, being the aggression harder for AIVA...

Uma nova técnica para avaliar a lesão endotelial na arteriosclerose / A new technique to evaluate the endotelium lesion in atheroesclerosis

Os autores propõem uma nova técnica para avaliar a relação entre infecção e aterosclerose pela coleta de sangue da artéria coronária depois da lesão ou do seio coronariano em casos de insuficiência coronariana aguda durante a angioplastia, buscando bactérias, vírus e fragmentos de DNA virais

Patogénesis de la endocarditis infecciosa / Pathogenesis of infectious endocarditis

Se discuten los mecanismos moleculares que llevan a la formación de las lesiones más características de la Endocarditis Infecciosa, en especial, la formación de vegetaciones y los diferentes mediadores involucrados provenientes de los gérmenes causales.

Von Willebrand factor as marker of endothelial dysfunction in non - insulin - dependent diabetes mellitus.

This study evaluated the plasma level of von Willebrand factor [vWF] in non-insulin-dependent diabetes mellitus [NIDDM] patients with and without microalbuminuria [MA] to elucidate whether MA is a consequent of endothelial injury. This work was enrolled on 30 NIDDM patients classified into three groups, each including 10 age matched subjects. Group I included normoalbuminuric patients, group II included microalbuminuric patients and group III included microalbuminuric patients complicated by coronary artery disease [CAD], in addition to 10 healthy normoalbuminuric age matched control subjects. Von Willebrand factor, malondialdehyde [MDA], vitamin C, erythrocyte reduced glutathione [GSH], albumin execration rate [AER], total cholesterol, LDL and HDL cholesterol, urea and creatinine were measured in all patients groups and control group. It can be concluded that NIDDM is characterized by many metabolic disorders including excessive oxidative stress, deficiency of antioxidants and dyslipidemia, resulting in endothelial injury, which can be marked by an elevation of vWF level even before the development of microalbuminuria. Thus, microalbuminuria might be considered a consequence of endothelial dysfunction

Clinical significance of measurements of serum and urinary thrombomodulin and serum e-selectin in diabetic patients with and without complications

Serum and urinary levels of soluble thrombomodulin [TM] and the serum levels of the soluble leucocyte adhesion molecule E-selectin, were measured in 80 diabelic patients. Fourty patients with insulm-dependent diabetes mellitus [IDDM] were divided into 20 non-complicated patients [group I] and 20 complicated patients [group II]. Ten age-matched healthy subjects were used as a control [group III] for the IDDM patients. Another 40 patients with non-insulin-dependent diabetes mellitus [NIDDM] comprised 20 non-complicated patients [group IV] and 20 complicated patients [group V]. Ten more age-matched healthy subjects were selected as a control [group VI] for the NIDDM patients. Serum and urinary concentrations of TM were significantly higher in diabetic patients compared with controls. Moreover, serum and urinary TM levels were significantly increased in complicated IDDM and NIDDM patients compared with the non-complicaied patients and the control subjects. Similarly, serum concentrations of E-selectin were found to be significantly higher in complicated diabetic patients versus the non-complicated patients and the control groups. In all diabetic patients of the four studied groups and in each separale group, serum and urinary levels of TM and serum E-selectin concentrations correlated positively with the duration of diabetes, fasting and postprandial blood glucose, HbA[IC] and urinary albumin excretion. A significant positive correlation was also found between urinary and serum levels of TM in the four studied groups of patients. Furthermore, serum and urinary levels of TM together with serum E-selectin concentrations correlated positively with the frequency of complications in complicated IDDM and NIDDM patients. The results suggest that serum and urinary TM levels could be a sensitive and predictive marker for the generalized vascular endothelial mjury induced by hyperglycemia and/or premicroangiopathy in diabetic patients. The present data point to a functional role for the soluble leucocyte adhesion molecule E-selectin in the development and progressions! complications in diabetic patients. The results also indicate that the concentrations of TM and E-selectin may be retated to metabolic control

Von Willebrand factor: a biomarker of endothelial cell damage in dehydrated and malnourished children

The level of von Willebrand factor [vWF] as a marker of endothelial cell injury was evaluated in 73 children with age ranged from 3 to 30 months. Twenty-three cases suffered from dehydration, nineteen from marasmus, twelve from Kwashiorkor [KWO] and nineteen healthy children were included as controls. In both dehydrated and malnourished groups, the level of vWF was highly significantly elevated than the control group. A strong negative correlation was found between vWF and each of hemoglobin level, hematocrit, red blood cell count as well as several anthropometric Z scores [HAZ, WAZ and BMI]. The prothrombin concentration also correlated significantly and negatively with vWF level. In the dehydration group, vWF level correlated strongly and positively with the score of clinical severity. This work demonstrated that the integrity of the endothelium is likely to be affected in dehydration and malnutrition where pathologic unfavorable conditions are likely to exist. The measurement of vWF levels in such conditions proved to be benefit in accurate assessment as well as prognosis

Role of helicobacter in bile induced injury to gastric endothelium

Forty patients were included in this study [22 men and 18 women]. Patients showed variant forms of endoscopic findings ranging from normal finding to severe gastritis or duodenal ulcer. 24 patients [24/40] proved to be Helicobacter pylori [HP] positive by rapid urease test [60%]. Eighteen patients of them [18/24] were gram +ve [75%]. Patients showed bile reflux with bile acid> 1 mmol/I were 24 [24/40] of total [60%], 19 of them were HP positive by rapid urease test [79.1%], 16 of them were also gram +ve for HP, those 16 patients which were DGR +ve, urease +ve and gram +ve were subjected to treatment protocol of triple therapy for 2 weeks. Follow up was done after one month of the end of treatment. 10 patients with DGR showed marked reduction in bile acid concentration [<1 mmol/L], while the rest showed no changes. 13 patients became H. pylori -ve. All DGR -ve patients became H. pylori -ve [P> 0.05]. Histopathological examination of antral biopsy showed no inflammatory responses in 8 patients after eradication of H. pylori [n = 13]