Clinical value of combined detection of thrombus precursor protein and P-selectin in the diagnosis of acute coronary syndrome / Valor clínico de la detección combinada de proteína precursora de trombo y selectina P en el diagnóstico del síndrome coronario agudo

Abstract Acute coronary syndrome (ACS), including acute myocardial infarction (AMI) and unstable angina (UA), is the most threatening and lethal form of coronary heart disease. ACS has an abrupt onset and rapid development, which may lead to fatal conditions at any time. Thus, it is never too early to detect and diagnose patients with ACS. The objective of this work was to explore the significance of the combined detection of plasma thrombus precursor protein (TpP) and serum P-selectin (Ps), in the detection and diagnosis of patients with early ACS. A total of 126 subjects were included in the study, 64 ACS patients, 30 individuals with stable angina (SA) and 32 healthy persons who were selected as the control groups. There were no differences in gender, age, ethnicity, or blood glucolipid levels among the groups. Enzyme linked immunosorbent assay (Elisa) was used to quantitatively determine the plasma levels of TpP and Ps. The levels of the two biomarkers in the case group were significantly higher than those in the control groups. Among the ACS patients, the levels of TpP and Ps were higher in AMI patients than in the UA patients. In addition, there was no significant differences in the levels of Ps between SA patients and healthy persons. In conclusion, plasma TpP and serum Ps are remarkably increased in patients with ACS. Therefore, TpP and Ps may serve as ACS indicators, and their measurement may provide a support for an early clinical identification of ACS.

Resumen El síndrome coronario agudo (SCA), que incluye el infarto agudo de miocardio (IAM) y la angina inestable (AI), es la forma más amenazante y letal de enfermedad coronaria. El SCA tiene un inicio abrupto y un desarrollo rápido, lo que puede conducir a condiciones fatales en cualquier momento. Por lo tanto, nunca es demasiado pronto para detectar y diagnosticar pacientes con SCA. El objetivo de este trabajo fue explorar la importancia de la detección combinada de la proteína precursora de trombos plasmáticos (TpP) y la selectina P sérica (Ps), en la detección y diagnóstico de pacientes con SCA precoz. Se incluyeron en el estudio un total de 126 sujetos, 64 pacientes con SCA, 30 individuos con angina estable (AE) y 32 personas sanas que fueron seleccionadas como grupos de control. No hubo diferencias en el género, la edad, el origen étnico o los niveles de glucolípidos en sangre entre los grupos. Se usó el ensayo inmunoabsorbente ligado a enzimas (Elisa) para determinar cuantitativamente los niveles plasmáticos de TpP y Ps. Los niveles de los dos biomarcadores en el grupo de casos (SCA) fueron significativamente más altos que los de los grupos de control. Entre los pacientes con SCA, los niveles de TpP y Ps fueron más altos en los pacientes con IAM que en los pacientes con AI. Además, no hubo diferencias significativas en los niveles de Ps entre pacientes con SA y personas sanas. En conclusión, la TpP plasmática y la Ps sérica están notablemente aumentadas en pacientes con SCA. Por lo tanto, TpP y Ps pueden servir como indicadores de SCA y su medición puede proporcionar un apoyo para una identificación clínica temprana de SCA.

A hiperemia reativa correlaciona-se com presença de sepse e degradação de glicocálix na unidade de terapia intensiva: um estudo de coorte prospectiva / Reactive hyperemia correlates with the presence of sepsis and glycocalyx degradation in the intensive care unit: a prospective cohort study

RESUMO Objetivo: Investigar se a hiperemia reativa correlaciona-se com marcadores de disfunção endotelial e pode ser utilizada para identificar sepse na doença crítica. Métodos: Trata-se de estudo prospectivo em uma coorte de pacientes críticos. A disfunção endotelial foi avaliada quando da admissão, por meio da quantificação de hiperemia por tonometria arterial periférica e níveis plasmáticos de endotelina 1, E-selectina solúvel, endocana e sindecano 1. Os pacientes sépticos foram comparados com pacientes sem evidência de infecção. Resultados: Cinquenta e oito pacientes sépticos foram comparados com 28 controle. O logaritmo natural da tonometria arterial periférica teve correlação negativa com comorbidades cardiovasculares, severidade da doença e níveis plasmáticos de E-selectina solúvel (p = 0,024) e sindecano 1 (p < 0,001). O logaritmo natural da tonometria arterial periférica foi mais baixo nos pacientes sépticos quando comparado com os de pacientes controle (0,53 ± 0,48 versus 0,69 ± 0,42, respectivamente) e, quando ajustado à idade, o modelo multivariado predisse que cada 0,1 de diminuição em unidades de logaritmo natural da tonometria arterial periférica levou a aumento de 14,6% na probabilidade de infecção. Conclusão: A hiperemia reativa avaliada por tonometria arterial periférica tem estreita relação com E-selectina solúvel e sindecano 1, o que sugere associação entre ativação endotelial, degradação de glicocálix e reatividade vascular. A hiperemia reativa por tonometria arterial periférica parece estar comprometida em pacientes críticos, especialmente os com sepse.

Abstract Objective: To investigate whether reactive hyperemia measured by peripheral arterial tonometry correlates with markers of endothelial dysfunction and may be used to identify sepsis in critical illness. Methods: A prospective study was performed using a cohort of critically ill patients. Endothelial dysfunction was assessed on admission by quantifying reactive hyperemia-peripheral arterial tonometry and plasma levels of endothelin-1, soluble E-selectin, endocan and syndecan-1. Septic patients were compared to patients without evidence of infection. Results: Fifty-eight septic patients were compared to 28 controls. The natural logarithm of reactive hyperemia-peripheral arterial tonometry was negatively correlated with cardiovascular comorbidities, disease severity and plasma levels of soluble E-selectin (p = 0.024) and syndecan-1 (p < 0.001). The natural logarithm of reactive hyperemia-peripheral arterial tonometry was lower in septic patients than in controls (0.53 ± 0.48 versus 0.69 ± 0.42, respectively). When adjusted for age, the multivariable model predicted that each 0.1-unit decrease in natural logarithm of reactive hyperemia-peripheral arterial tonometry increased the odds for infection by 14.6%. m. Conclusion: Reactive hyperemia-peripheral arterial tonometry is closely related to soluble E-selectin and syndecan-1, suggesting an association between endothelial activation, glycocalyx degradation and vascular reactivity. Reactive hyperemia-peripheral arterial tonometry appears to be compromised in critically ill patients, especially those with sepsis.

Adhesion molecules before and after propylthiouracil in patients with subclinical hyperthyroidism

SUMMARY OBJECTIVE This study aimed to investigate the effect of propylthiouracil treatment on adhesion molecules in patients with subclinical hyperthyroidism. METHODS In this study, a total of 168 patients diagnosed with subclinical hyperthyroidism were treated with propylthiouracil for one year. The levels of adhesion molecules, consisting of sICAM-1, sVCAM-1, and sE-Selectin, before and after the treatment were measured and compared. These results were compared with the levels of 148 healthy controls who received a placebo. RESULTS sICAM-1 levels were significantly higher in subclinical hyperthyroidism patients than in healthy controls (*pa=0.000). sICAM-1 levels were significantly decreased after the treatment (**pb=0.000). Despite this decrease in patients with subclinical hyperthyroidism, it did not decrease to the level of the control group. sVCAM-1 did not change before and after propylthiouracil treatment. The level of sE-selectin was similar to that of the pretreatment control group, but it did not have statistical significance, although it increased after the treatment (**pb=0.004). CONCLUSION The sICAM level was significantly higher than the pretreatment values and decreased after the propylthiouracil treatment. However, further studies are needed to reduce the risk of atherosclerosis and cancer in patients with subclinical hyperthyroidism.

RESUMO ANTECEDENTES O objetivo deste estudo foi investigar o efeito do tratamento com propiltiouracil nas moléculas de adesão em pacientes com hipertireoidismo subclínico. MÉTODOS Neste estudo, 168 pacientes diagnosticados com hipertireoidismo subclínico foram tratados com propiltiouracil por um ano. Os níveis de moléculas de adesão, especificamente sICAM-1, sVCAM-1 e sE-Selectina, antes e após o tratamento foram medidos e comparados. Esses resultados foram comparados com os níveis de 148 indivíduos saudáveis no grupo de controle que receberam um placebo. RESULTADOS Os níveis de sICAM-1 foram significativamente maiores em pacientes com hipertireoidismo subclínico do que nos controles saudáveis (*pa=0,000). Os níveis de sICAM-1 diminuíram significativamente após o tratamento (**pb=0,000). Apesar dessa diminuição em pacientes com hipertireoidismo subclínico, ela não diminuiu para o nível do grupo controle. O sVCAM-1 não se alterou antes e após o tratamento com propiltiouracil. O nível de sE-Selectina foi semelhante ao do grupo de controle pré-tratamento, mas não apresentou significância estatística, embora tenha aumentado após o tratamento (** pb = 0,004). CONCLUSÃO O nível de sICAM foi significativamente superior aos valores pré-tratamento e diminuiu após o tratamento com propilciliouracil. No entanto, mais estudos são necessários para reduzir o risco de aterosclerose e câncer em pacientes com hipertireoidismo subclínico.

Ativação endotelial na granulomatose com poliangeíte (granulomatose de Wegener) / Endothelial activation in granulomatosis with polyangiits

INTRODUÇÃO: Eventos vasculares e imunológicos são centrais na patogênese da granulomatose com poliangeíte (GPA). Moléculas de adesão celular tem papel fundamental no recrutamento de células inflamatórias do sangue para os tecidos. Diferentes leitos vasculares apresentam particularidades na expressão de moléculas de adesão celular explicando talvez parte da especificidade da GPA por determinados órgãos. A elevação no nível sérico de moléculas de adesão celular e aumento da expressão destas em amostras de biópsia renal já foram demonstrados em pacientes com vasculite ANCA associada. No entanto, o fenômeno ainda não foi estudado in situ no pulmão. OBJETIVO: O objetivo deste estudo foi analisar o padrão de expressão endotelial pulmonar de três moléculas de adesão celular na GPA, in situ: molécula de adesão intercelular 1 (ICAM-1), molécula e adesão vascular 1 (VCAM-1) e E-selectina. MÉTODOS: Examinou-se a expressão endotelial de ICAM-1, VCAM-1, E-selectina usando marcação imuno-histoquímica em secções de pulmão fixadas e parafinadas de lesões de GPA (n = 8 casos, 90 secções transversais de vasos analisados). Foram também analisados controles positivos: amostras de pulmão de doença intersticial associada à esclerodermia (SScl) (n = 8 casos, 96 secções transversais de vasos analisados) e controles negativos (n = 9 casos, 90 secções transversais de vasos analisados). A quantificação imuno-histoquímica foi realizada no aumento de 400x usando a técnica de point-counting. RESULTADOS: ICAM-1: A expressão endotelial mediana de ICAM-1 esteve aumentada de forma semelhante na GPA e na SScl (81% and 73%, respectivamente; p = 0.97). A comparação com o grupo controle (26.3%) revelou diferença estatisticamente significativa entre controle e GPA (p <0.001) quanto entre controle e SScl (p = 0.017). VCAM-1: A expressão mediana de VCAM-1 esteve significativamente aumentada na GPA se comparada a SScl (79.5% vs 41.4%; p = 0.012), no entanto, a expressão endotelial de VCAM-1 nos...

INTRODUCTION: Vascular and immunologic processes are central to the pathogenesis of granulomatosis with polyangiitis (GPA). Endothelial cellular adhesion molecules have a central role in recruiting leukocytes to sites of inflammation. Moreover, different vascular beds are phenotypically and functionally distinct with regard to expression of cellular adhesion molecules. They have been shown to be elevated in sera and in renal biopsies of patients with active ANCA-associated vasculitis. Despite of that, the expression of cellular adhesion molecules has not been studied in situ in the lungs. OBJECTIVE: Within this context, the aim of this study was to analyze the in situ pulmonary endothelial immunohistochemical pattern of expression of three cellular adhesion molecules in GPA: intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and E-selectin . METHODS: For such, we examined formalin-fixed, paraffin-embedded sections of lung lesions of GPA (n = 8 cases, 90 transverse sections of pulmonary vessels), negative controls which were obtained from autopsies ( n = 9 cases, 90 transverse sections of pulmonary vessels analyzed) and positive controls which were cases of interstitial lung disease associated with systemic sclerosis (SScl) (n = 8 cases, 96 transverse sections of pulmonary vessels). The quantification of the immunohistochemical staining was performed at x400 magnification using the technique of point-counting, previously described. RESULTS: ICAM-1: Median endothelial expression of ICAM-1 was similarly enhanced in GPA and SScl (81% and 73%, respectively; p = 0.97). When compared to controls (26.3%), both GPA (p <0.001) and SScl (p = 0.017) had significantly higher endothelial expression of ICAM-1. VCAM-1: Median endothelial expression of VCAM-1 was significantly enhanced in GPA when compared to SScl (79.5% vs 41.4%; p = 0.012), however the endothelial expression of VCAM-1 in the controls was also moderately enhanced (49.8%)...

Estudo dos efeitos do etil-piruvato, salina hipertônica e do Ringer lactato sobre a resposta da microcirculação mesentérica em modelo de sepse induzida por Escherichia coli em ratos / Effects of ethyl-pyruvate, hypertonic saline and lactated Ringer's solution on mesenteric microcirculation in a sepsis model induced by Escherichia coli in rats

INTRODUÇÃO: Estudos recentes em modelos experimentais de sepse demonstraram as propriedades antioxidante e anti-inflamatória do etilpiruvato. Diferentes modelos experimentais também demonstraram que pequenos volumes de solução salina hipertônica (7,5%) melhoram a hemodinâmica, a microcirculação e modulam o sistema imunológico. Este estudo teve como objetivo investigar os efeitos do etil-piruvato, da solução salina hipertônica e da solução de Ringer lactato sobre a microcirculação mesentérica em modelo de sepse induzida por Escherichia coli viva em ratos. MÉTODOS: Ratos Wistar machos receberam por via endovenosa uma suspensão de E. coli ou foram submetidos ao procedimento cirúrgico do grupo falso-operado. Após três horas da infusão bacteriana os animais foram randomizados em: grupo controle não tratado, grupo tratado com solução de Ringer lactato (4mL/kg i.v.); grupo tratado com solução de Ringer lactato (4 mL/kg i.v.) associado a etil-piruvato (50mg/kg) e grupo tratado com solução salina hipertônica (7,5%, 4 mL/kg i.v.). Após 24 horas da bacteremia, as interações leucócito-endotélio foram investigadas por microscopia intravital, e a expressão de P-selectina e da molécula de adesão intercelular (ICAM)-1 determinada por imuno-histoquímica. Leucograma e contagem de plaquetas foram realizadas no início do estudo, 3 horas e 24 horas após a inoculação de E. coli. RESULTADOS: Os grupos não tratado e tratado com solução de Ringer lactato exibiram um aumento no número de leucócitos rollers (~ 2,5 vezes), leucócitos aderidos (~ 3,0 vezes), e de leucócitos migrados (~ 3,5 vezes) comparados ao grupo falso operado. O tratamento com etil-piruvato reduziu o número de leucócitos rollers, aderidos e migrados aos níveis obtidos no grupo falso operado (p > 0,05). Efeitos semelhantes foram observados nos animais tratados com a solução salina hipertônica (p > 0,05). A expressão de P-selectina e de ICAM-1 aumentou significativamente na microcirculação mesentérica no grupo...

BACKGROUND: Experimental studies on sepsis have demonstrated that ethyl pyruvate is endowed with antioxidant and anti-inflammatory properties. It has been shown that small volumes of hypertonic saline solution (7.5%) improve hemodynamics, the microcirculation, and modulate the immune system. This study aimed to investigate the effects of ethyl pyruvate, hypertonic saline and lactated Ringer's solution on mesenteric microcirculation in a sepsis model induced by live Escherichia coli in rats. METHODS: Male Wistar rats were underwent an intravenous suspension of E. coli bacteria or submitted to the sham procedure. After 3h of bacteria infusion rats were randomized into: control, without treatment; treated with lactated Ringer's solution (4 mL/kg, i.v.); treated with lactated Ringer's solution (4mL/kg, i.v.) plus ethyl pyruvate (50mg/kg), and treated with hypertonic saline solution (7.5%, 4 mL/kg i.v.). At 24h after bacteria infusion leukocyte-endothelial interactions were investigated by intravital microscopy, and the expression of P-selectin and intercellular adhesion molecule (ICAM)- 1 evaluated by immunohistochemistry. White blood cell and platelet counts were determined at baseline, 3h and 24h after E. coli inoculation. RESULTS: Both non-treated and lactated Ringer's-treated groups exhibited an increase in the number of rolling leukocytes (~2.5-fold), adherent (~3.0-fold), and migrated cells (~3.5-fold) compared to sham. Treatment with Ringer's ethyl pyruvate solution reduced the number of rolling, adherent and migrated leukocytes to the levels attained in the sham group (p > 0.05). Similar effects were observed when animals were treated with hypertonic saline (p > 0.05). The expression of P-selectin and ICAM-1 significantly increased on mesenteric microvessels in non-treated group compared with sham (p < 0.001). All treatments reduced the expression of both adhesion molecules being ethyl pyruvate and hypertonic saline solution...

Niveles elevados de e-selectina soluble en una población infantojuvenil con sobrepeso / Elevated Soluble E-selectin levels in an Infant-juvenile Population with Overweight

El sobrepeso infantil se asocia a sobrepeso/obesidad en la edad adulta y constituye un factor de riesgo de diabetes y enfermedad cardiovascular. La disfunción endotelial es la etapa inicial de ateroesclerosis y precede a las evidencias anatómicas más tempranas de la misma. Este proceso está regulado por moléculas de adhesión localizadas en la superficie de leucocitos y células endoteliales y que tendrían un papel importante en la predicción de los eventos cardiovasculares. Entre estas moléculas, la E-Selectina (E-S) es una glicoproteína que se expresa exclusivamente en las células endoteliales activadas, en respuesta a citoquinas inflamatorias. Se ha sugerido que niveles aumentados de forma solubles de E-Selectina (sE-S) podrían ser marcadores específicos del endotelio vascular dañado. El objetivo de este trabajo fue determinar los niveles plasmáticos de sE-S en niños y adolescentes con sobrepeso y su relación con variables antropométricas y bioquímicas. Se estudiaron 40 niños con sobrepeso, de edades comprendidas entre 7 y 14 años y 20 niños controles de edad y sexo semejantes. Se consideró criterio de inclusión un IMC ≥ al percentilo 85 y menor al percentilo 95 para edad y sexo. Se determinó circunferencia de cintura (CC), IMC, estadio de Tanner y presión arterial. En ambos grupos se analizó: glucemia en ayunas, insulina plasmática, fibrinógeno (Fg), proteína C reactiva ultrasensible (uPCR), sE-S en plasma y perfil lipídico. Los datos se expresaron como mediana y rango intercuartil, empleándose el coeficiente de Spearman para las correlaciones entre variables. En los sujetos con sobrepeso fueron mayores los niveles de sE-S [72,0 (50,5-92,5) vs. 24,0(18,5-35,0) ng/ml; p = 0,0001], uPCR [1,9 (0,8-4,4) vs. 0,3 (0,2-1,1) mg/l; p = 0,001], Fg [350 (315-460) mg/dl vs. 247 (235-265) mg/dl; p = 0,0001]. También resultaron elevados los valores de insulina y triglicéridos. La sE-S se correlacionó con CC (r = 0,40; p = 0,02), uPCR (r = 0,58; p = 0,0001) y Fg (r = 0,50; p = 0,004). Estos resultados sugieren la presencia de activación endotelial y estado proinflamatorio en la población estudiada, destacándose la importancia del control del peso en los niños con el fin de reducir el riesgo cardiovascular en la adultez. Los autores declaran no poseer conflictos de interés.

Childhood overweight is associated to overweight/obesity adulthood and it is a risk factor for diabetes and cardiovascular disease. Endothelial dysfunction is the initial stage of atherosclerosis and precedes earliest anatomical evidence thereof. This process is regulated by adhesión molecules located on the surface of leucocytes and endothelial cells and would have an important role in the prediction of cardiovascular events. Between these molecules, E-selectin (E-S) is a glycoprotein that is express exclusively on activated endothelial cells in response to inflammatory cytokines. It has suggested that increases of soluble form of E-S (sE-S) could be an specific marker of damaged vascular endhotelium. The aim of this study was determine plasma levels of sE-S in overweight children and its relationship with anthropometric and biochemical variables. Forty overweight children aged between 7 to 14 years, and 20 control children of similar age and sex, were studied. Inclusión criteria was a BMI ≥ 85th percentile and below 95th percentile, for age and sex. Waist circunference (WC), BMI, Tanner stage and blood pressure were determined. In both groups fasting blood glucose and insulin, fibrinogen (Fg), high sensitivity C-reactive protein (hsCRP), sE-S and lipid profile were analyzed. The data were analyzed with the SPSS 15.0 program for Windows, expressed as the median and interquartile range. The Spearman's coefficient were used to measure correlations between the studied variables. Overweight subjects presented higher levels of sE-S [72.0 (50.5-92.5) vs. 24.0 (18.5-5,0) ng/ml, p = 0.0001], hsCPR [1.9 (0.8-4.4) vs. 0.3 (0.2-1.1) mg/l, p = 0.001], Fg [350 (315-460) vs. 247 (235-265) mg/dl, p = 0.0001]. Also insulin and triglycerides values were elevated. sE-S was correlated positivily with WC (r = 0.40, p = 002), hs PCR (r = 0.58, p = 0.0001) and Fg (r = 0.50, p = 0.004). These results suggest the presence of endothelial activation and a proinflammatory state in the studied population, and highlight the importance of weight control in children to reduce cardiovascular risk in adulthood. The authors do not have conflicts of interest.

E-selectina soluble en una población infanto-juvenil con diabetes tipo 1 / Soluble E- selectin in children and adolescents with type 1 diabetes

El estado de hiperglucemia crónica en los pacientes diabéticos produce una agresión al endotelio vascular, conduciendo al desarrollo prematuro de ateroesclerosis. El objetivo de este trabajo fue determinar niveles de E-selectina soluble (sE-S) en una población infanto-juvenil con diabetes tipo1 (DT1) y su relación con el control glucémico y el perfil lipídico. Se estudiaron 30 pacientes con DT1 (16 mujeres y 14 varones), de edades comprendidas entre 6 y 15 años, comparados con 20 sujetos controles. Se determinaron: sE-S, glucemia en ayunas, hemoglobina glicosilada (HbA1c), colesterol total (CT), HDL-C, LDL-C, no HDL-C y triglicéridos (TG). Los niveles de sE-S fueron 66% más altos en los diabéticos que en los sujetos controles (p = 0.0001). Los pacientes fueron agrupados en: diabéticos con buen control glucémico (DBCG, HbA1c < 8%) y diabéticos con pobre control glucémico (DPCG, HbA1c > 8%). La concentración de sE-S en DPCG y en DBCG fue: 111.3 ± 40.5 vs. 68.0 ± 11.3 ng/ml, respectivamente p = 0.02. En los diabéticos la incidencia de valores no deseables en el perfil lipídico fue: CT: 50%; HDL-C 14%; LDL-C 52%, no HDL-C 26.7% y TG 14%. La sE-S se correlacionó mejor con HbA1c (r = 0.53, p = 0.0001) que con la glucemia en ayunas (r = 0.36, p = 0.008) y CT (r = 0.36, p = 0.009). De los resultados obtenidos se sugiere que la sE-S es un marcador temprano de disfunción endotelial y de probable riesgo de aterosclerosis en pacientes infanto-juveniles con DT1.

The chronic hyperglycemic state in diabetic patients produces an aggression to the vascular endothelium leading to a premature development of atherosclerosis. The objective of this paper was to determine the soluble E-selectin (sE-S) levels in children with type 1 diabetes (DT1) and its relationship with glycemic control and lipid profile. Thirty patients with DT1, (16 girls and 14 boys), age between 6 and 15 years were studied, whose data were compared with 20 control subjects. In both groups sE-S was determined as well as fasting glycemia, glycosylated hemoglobin (HbA1c), total cholesterol (TC), HDL-C, LDL-C, non-HDL-C and triglycerides (TG). sE-S values were 66% higher in diabetics than in control subjects (p = 0.001). Patients were grouped in: good glycemic control diabetics (GGCD, HbA1c < 8%) and poor glycemic control diabetics (PGCD, HbA1c > 8%). sE-S concentratios were in PGCD an GGCD respectively. 111.3 ± 40.5 vs 68.0 ± 11.3 ng/ml, p = 0.02. In the diabetic group, the incidence of non desirable values in the lipid profile parameters were: TC 50%; HDL-C 14%; LDL-C 52%, non-HDL-C 26.7% and TG 14%. sE-S values were better correlated with HbA1c (r = 0.53, p = 0.0001) than fasting glycemia (r = 0.36, p = 0.008), and CT (r = 0.36, p = 0.009). These results suggest that sE-S is an early marker of endothelial dysfunction and a probable risk marker of atherosclerosis in children with DT1.

Evaluación de disfunción endotelial en pacientes con diabetes tipo 2 / Dysfunction endothelial evaluation in type 2 diabetes patients

El objetivo de este trabajo fue estudiar moléculas involucradas en la activación endotelial, tales como la molécula de adhesión sE-Selectina (sE-S) y el péptido vasoconstrictor Endotelina-1 (ET-1) en individuos diabéticos tipo 2 y su asociación con otros factores de riesgo cardiovascular. Se estudiaron 62 pacientes diabéticos que se compararon con un grupo control. Las concentraciones de sE-S y ET-1 fueron significativamente mayores en los diabéticos que en los controles (sE-S: 90,6±26,2 ng/mL vs. 49,5±9,2 ng/mL, p<0,00001; ET-1: 11,3±3,7 vs. 7,7±0,5 pg/mL, p<0,001, respectivamente). Estas moléculas, en pacientes con índice de masa corporal (IMC) normal y aumentado, mostraron diferencias significativas (sE-S: 75,5±22,4 vs. 97,1±32,9 ng/mL, p<0,05; ET-1: 8,4±2,4 vs. 14,1±4,9 pg/mL, p=0,001, respectivamente). No se encontraron diferencias entre individuos diabéticos normo e hipertensos, no fumadores y fumadores, ni normo e hipercolesterolémicos. El 81% de la población estudiada presentó un pobre control glucémico (HA1c>7%), siendo significativamente mayores los niveles de ET-1 en este grupo (p<0,01) no así para sE-S (p=0,74). Los resultados obtenidos muestran que los pacientes diabéticos presentan activación endotelial reflejada en los niveles elevados de sE-S y ET-1. El IMC aumentado y el pobre control glucémico incrementan la disfunción endotelial en estos pacientes.

The object of this work was to study molecules involved in endothelial activation, such as E-selectin (sE-S) and the vasoconstrictor peptide Endothelin-1 (ET-1) in Type 2 diabetes patients, and their relation with other cardiovascular risk factors. Sixty-two patients with diabetes were compared with matched controls. sE-S and ET-1 concentrations in diabetes patients were significantly elevated compared with controls (sE-S: 90.6±26.2 ng/mL vs 49.5±9.2 ng/mL, p<0.00001; ET-1: 11.3±3.7 vs 7.7±0.5 pg/mL, p<0.001, respectively). sE-S and ET-1 levels in diabetes patients with normal and increased body mass index showed significant differences (sE-S: 75.5±22.4 vs. 97.1±32.9 ng/mL, p<0.05; ET-1: 8.4±2.4 vs. 14.1±4.9 pg/mL, p=0.001 respectively). There were no significant differences in none of the molecules values between patients with or without hypertension, smokers or non-smokers, neither in diabetes patients with or without hypercholesterolemia. Eighty-one percent of the population with diabetes presented a poor glycemic control (HA1c>7%) and in these patients, ET-1 plasma levels were significantly increased (p<0.01), but not sE-S (p=0.74). These results show that obesity and a poor glycemic control increase the endothelial dysfunction in type 2 diabetes patients.

Participação das plaquetas no processo de fibrose dos pacientes com esquistossomose mansônica / Participation of platelets in the process of fibrosis in patients with mansonic schistosomiasis

O objetivo deste estudo foi avaliar a ativação plaquetária através da P-selectina e o conteúdo de PDGF-AB e TGFbeta1, nos pacientes com esquistossomose que desenvolveram fibrose (F3), naqueles que não tiveram esta manifestação (F0) e nos controles (C). Os resultados mostraram que a percentagem de P-selectina nas plaquetas sem estímulo de agonistas foi de 10,6 por cento nos F3; 11,1 por cento nos FO, e 6,3 por cento nos C e após a adição de ADP/adrenalina, foi de 44 por cento; 25,3 por cento e 42 por cento, respectivamente. A dosagem do PDGF-AB e TGFbeta1 por plaquetas foi de 11,016ng/dL (F3); 3,172 ng/dL (F0) e 5,01ng/dL (C) e, (0,012ng/dL (F3); 5,27ng/dL (F0) e 4,66ng/dL (C), respectivamente. Em relação à P-selectina, concluímos que as plaquetas dos pacientes com esquistossomoses, apesar de estarem pré ativadas, mantiveram-se responsivas aos agonistas. O TFGbeta1 não apresentou diferença entre os três grupos, enquanto o PDGF-AB foi significantemente maior no grupo F3, sugerindo a participação deste no desenvolvimento da fibrose.

The aim of this study was to evaluate platelet activation through P-selectin, and PDGF-AB and TGFbeta1 content, in schistosomiasis patients who developed fibrosis (F3) and who did not present this (F0), and in a control group (C). The results showed that the percentage of P-selectin in platelets without agonist stimulation was 10.6 percent in F3, 11.1 percent in F0 and 6.3 percent in C. After the addition of ADP/adrenaline, the percentages were 44 percent, 25.3 percent and 42 percent, respectively. The PDGF-AB and TGFbeta1 contents per platelet were 11,016ng/dl (F3), 3,172ng/dl (F0) and 5.01ng/dl (C) and 0,012ng/dl (F3), 5.27ng/dl (F0) and 4.66ng/dl (C), respectively. Concerning the P-selectin, we can conclude that platelets from patients with schistosomiasis continued to be responsive to agonists, despite being pre-activated. There were no differences in TGFbeta1 between the groups, but the PDGF-AB content was significantly higher in F3. This suggests that PDGF-AB may have some participation in the development of fibrosis.