Is periostin useful as a biomarker for fibrous dysplasia? / ¿Es útil periostina como biomarcador de displasia fibrosa?

Fibrous dysplasia (FD) is an infrequent non-hereditary bone disease caused by a somatic mutation of the GNAS gene. Periostin is a novel marker that increases during tissue healing and fibrous or inflammatory diseases. We conducted an exploratory case-control study to evaluate sensitivity of periostin as a biomarker of FD. The study comprised 15 patients with FD, and healthy age- and sex-matched subjects (controls). Serum periostin levels were assessed and comparisons were established between FD patients and controls, and between patients with the monostotic and the polyostotic form of FD. No statistically significant differences in serum periostin levels were observed between the cohort of FD patients studied here and the control group (FD: 51.1±10ng/ml vs. control: 44.2±15ng/ml; p=0.15), or between the clinical forms of FD (polyostotic: 51.8±9.1ng/ml vs. monostotic: 49.6±13 ng/ml; p=0.66). A sub-analysis performed to compare serum levels of periostin in FD patients with and without a history of fractures showed no statistically significant differences [fracture patients (n=4): 41.2±17ng/ml vs. non-fracture patients (n=11): 49.9±11 ng/ml; p=0.47].Lastly, sensitivity of periostin as a biomarker of FD was analyzed, and was found to have low sensitivity to estimate disease activity [ROC curve; cut-off points: 39.625(0.867-0.467)]. To conclude, in the cohort of FD patients studied here, periostin serum levels did not differ significantly from those of the control group or between the two forms of the disease, and showed low sensitivity as a biomarker of the disease. (AU)

La displasia fibrosa (DF) es una enfermedad infrecuente del hueso, no hereditaria producida por una mutación somática del gen GNAS. Periostina (Postn) es un novedoso marcador, cuyos niveles séricos se encuentran elevados en los procesos de reparación tisular, enfermedades fibrosas o inflamatorias. Llevamos a cabo un estudio exploratorio caso-control para evaluar la sensibilidad de Postn como biomarcador de DF. Se incluyeron en el estudio 15 pacientes con DF apareados por edad y género con sujetos sanos (controles) en los cuales se evaluó los niveles séricos de Postn en pacientes con DF y controles y según forma de presentación clínica. No observamos diferencias estadísticamente significativas en los niveles séricos de Postn y el grupo control (DF: 51.1±10ng/ml vs. control: 44.2±15ng/ml; p=0.15) como así tampoco por forma clínica de DF (poliostótica: 51.8±9.1ng/ml vs. monos-tótica: 49.6±13 ng/ml; p=0.66). Posteriormente realizamos un sub-análisis para evaluar los niveles séricos de Postn en los pacientes con DF y antecedentes de fracturas no observan-do diferencias estadísticamente significativas [fracturados (n=4): 41.2±17ng/ml vs. no frac-turados (n=11): 49.9±11 ng/ml; p=0.47]. Por último analizamos la sensibilidad Postn como biomarcador de DF, mostrando este poseer escasa sensibilidad para estimar actividad de la enfermedad [curva ROC; puntos de corte: 39.625 (0.867-0.467)]. En conclusión, los ni-veles séricos de Postn en nuestra cohorte de pacientes con DF no mostraron diferencias estadísticamente significativas comparadas con el grupo control o por forma clínica de presentación, mostrando una baja sensibilidad como biomarcador de enfermedad. (AU)

Ginandroblastoma multiloculado, negativo para CD99 en una niña de 12 años: caso clínico / A twelve-years-old girl with multiloculated gynandroblastoma CD99 negative. Case report

Los ginandroblastomas son tumores del ovario extremadamente raros, los cuales comparten componentes de células de la granulosa y de células de Sertoli/Leydig. Se describe un caso de una niña de 12 años, quien presenta hemorragia uterina anormal y sensación de masa intraabdominal de crecimiento progresivo asociado a menorragia, niveles de CA-125 en 60,4 UI/mL y estudios de extensión que reportan masa quística en ovario izquierdo, manejada con ooforectomía. El estudio anatomopatológico muestra un tumor multiloculado lleno de material seroso, abundantes cuerpos de Call-Exner y 45% de células de Sertoli/Leydig. La inmunohistoquímica reveló inmunorreactividad para inhibina, calretinina y pCK, mientras que los marcadores CD99 y AE1/AE3 fueron negativos. Se trata del primer reporte de caso sobre un ginandroblastoma multiloculado, negativo para CD99 en una niña de 12 años, estudio que plantea un abordaje sistemático para los tumores de las células de los cordones sexuales.

The ginandroblastoma is an extremely rare ovarian tumor which shows components of granulosa cells and Sertoli/Leydig cells. We describe a case of a twelve-years-old girl who presented abnormal uterine bleeding and progressively growing intra- abdominal mass associated with menorrhagia, CA-125 60.4 UI/mL and extension studies reporting cystic mass in the left ovary. She underwent oophorectomy. Pathological study shows a multilocular tumor filled with serous material. Many Call-Exner bodies were observed in the histopathological analysis, 45% of Sertoli/Leydig cells. Immunohistochemistry was reactive for inhibin, calretinin and pCK while AE1/AE3 and CD99 markers were negative. This is the first case report about a multiloculated gynandroblastoma, negative for CD99 in a 12-years-old girl. Thus, the study of this clinical case represents a systematic approach for tumors of the sex cord cells.

Alteraciones de la hemostasia en el síndrome drepanocítico / Hemostasis alterations in sickle cell syndrome

El síndrome drepanocítico (SD) comprende un grupo de anemias hemolíticas hereditarias de tipo multisistémico asociadas a la hemoglobina S. Los pacientes que padecen este síndrome tienen un mayor riesgo, en comparación con individuos sanos, de presentar accidentes cerebrovasculares, hipertensión pulmonar, necrosis avascular de articulaciones, síndrome torácico agudo y complicaciones durante el embarazo, asociados a un estado de hipercoagulabilidad inducido por alteraciones en los diferentes componentes de la hemostasia, que incluyen la activación del endotelio y de los sistemas plaquetario, de la coagulación y de la fibrinólisis. Esta revisión resume las alteraciones en la hemostasia reportadas en los pacientes con SD, en los cuales se ha demostrado: mayor interacción de células endoteliales con leucocitos, hematíes y plaquetas; aumento de la expresión de proteínas de adhesión, como el factor von Willebrand y sus multímeros de alto peso molecular; aumento de la adhesión y la agregación plaquetaria y de la expresión de proteínas en sus membranas. En el sistema de coagulación se ha detectado aumento en la expresión del factor tisular (FT) en micropartículas derivadas de diferentes células, aumento de marcadores de activación de este sistema, entre estos los fragmentos 1.2 de la protrombina y los complejos trombina-antitrombina y una disminución de las proteínas C y S que actúan como anti-coagulantes. Adicionalmente, se han encontrado aumentados los marcadores de activación del sistema fibrinolítico como los dímeros D y los complejos plasmina/antiplasmina. Todas estas manifestaciones favorecen la aparición de complicaciones trombóticas, implicadas en el deterioro de la calidad de vida de los pacientes. Se recomienda implementar en el diagnóstico y seguimiento de esta enfermedad, la determinación de variables del sistema hemostático, con el fin de identificar alteraciones en etapas tempranas y aplicar terapias que puedan prevenir complicaciones trombóticas.

Sickle cell syndrome (SCS) includes a group of congenital hemolytic anemias associated to the presence of hemoglobin S, which is characterized by acute pain episodes and progressive damage of different organs. Some patients with sickle cell syndrome have shown, when compared with healthy individuals, an increased risk of presenting stroke, pulmonary hypertension, avascular necrosis of joints, acute chest syndrome and pregnancy complications, associated to a hypercoagulable state induced by alterations in different components of hemostasis, such as changes that include activation of the endothelium, platelet activity, coagulation and fibrinolytic systems. This paper compiles hemostasis disorders, associated with thrombotic manifestations, reported until now in sickle cell syndrom. These patients have an increase in activation markers of the coagulation system, such as prothrombin fragment 1.2, thrombin-antithrombin complex, etc., depletion of natural anticoagulant proteins, abnormal activation of the fibrinolytic system and increased tissue factor expression. Similarly, abnormal expression of glycoproteins and increased adhesion and platelet aggregation have been reported. All these alterations produce a hypercoagulable state, which induces, among other things, the appearance of thrombotic complications. In view of the importance of controlling the different complications that can occur in patients with sickle cell syndrome, we recommend the implementation, in diagnosis and monitoring studies, of the evaluation of the different components of the hemostatic system, identifying alterations at an early stage and applying effective treatments to prevent thrombotic complications.

Evaluation of Toll-like, chemokine, and integrin receptors on monocytes and neutrophils from peripheral blood of septic patients and their correlation with clinical outcomes

Recognition of pathogens is performed by specific receptors in cells of the innate immune system, which may undergo modulation during the continuum of clinical manifestations of sepsis. Monocytes and neutrophils play a key role in host defense by sensing and destroying microorganisms. This study aimed to evaluate the expression of CD14 receptors on monocytes; CD66b and CXCR2 receptors on neutrophils; and TLR2, TLR4, TLR5, TLR9, and CD11b receptors on both cell types of septic patients. Seventy-seven septic patients (SP) and 40 healthy volunteers (HV) were included in the study, and blood samples were collected on day zero (D0) and after 7 days of therapy (D7). Evaluation of the cellular receptors was carried out by flow cytometry. Expression of CD14 on monocytes and of CD11b and CXCR2 on neutrophils from SP was lower than that from HV. Conversely, expression of TLR5 on monocytes and neutrophils was higher in SP compared with HV. Expression of TLR2 on the surface of neutrophils and that of TLR5 on monocytes and neutrophils of SP was lower at D7 than at D0. In addition, SP who survived showed reduced expression of TLR2 and TLR4 on the surface of neutrophils at D7 compared to D0. Expression of CXCR2 for surviving patients was higher at follow-up compared to baseline. We conclude that expression of recognition and cell signaling receptors is differentially regulated between SP and HV depending on the receptor being evaluated.

[Association between legume consumption and circulating levels of adhesion molecules and inflammatory biomarkers among Iranian women]

Due to low consumption of leguminous foods across populations, not much information is available on possible independent role of legumes in inflammation. The traditional Iranian diet provides an opportunity to investigate possible association between intake of legumes and health. This study was carried out to determine the association between legume consumption and the serum levels of adhesion molecules and inflammatory biomarkers in Iranian women. In this cross-sectional study, trained dietitians administered a validated semiquantitative food frequency questionnaire [FFQ] for assessment of usual dietary intakes in a sample of 486 Tehranian female- teachers aged 40-60 years selected by a multistage cluster random sampling method. Legumes in the FFQ included lentils, peas, chickpeas, different kinds of beans [broad beans, etc.], and chickling vetch. Blood samples were taken to measure the plasma concentrations of adhesion molecules and inflammatory biomarkers. After controlling for potential confounders, including dietary variables, as compared to women with the lowest legume intake, those with the highest legume intake had lower circulating levels of Eselectin [percent difference from bottom quintile [-14.1%, p-trend=0.04], soluble intercellular adhesion molecule-1 [sICAM-1] [-20.3%, p-trend<0.01], and soluble vascular cell adhesion molecule-1 [sVCAM- 1] [-15.6%, p-trend=0.01]. Subjects in the top tertile of legume intake had lower serum levels of high sensitive C-reactive protein [hs-CRP], TNF- alpha and interleukin-6 [IL-6] as compared to those in the lowest tertile, even after controlling for potential confounders and dietary variables. No significant association was found between legume intake and serum amyloid A levels. High legume consumption is associated with low circulating levels of adhesion molecules and inflammatory biomarkers among Iranian women

Inflammation and endothelial activation in benign prostatic hyperplasia and prostate cancer

PURPOSE: Emerging insights underline a link among chronic inflammation and endothelial activation with benign prostatic hyperplasia (BPH) and prostate cancer (PCa). We aim to investigate whether specific plasma markers of inflammation and endothelial activation allow to discriminate BPH and PCa. MATERIALS AND METHODS: Fifteen patients affected by BPH, 15 by PCa and 15 controls, were enrolled. Interleukin-6 (IL-6), CD40 ligand (CD40L), endothelial-selectin (E-selectin), platelet-selectin (P-selectin), vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) were measured. RESULTS: In systemic blood samples, IL-6 has been found increased in patients affected by BPH (4.25 ± 0. pg/mL) and PCa (5.08 ± 0.24) respect to controls (2.62 ± 0.34; p < 0.05). CD40L was higher in BPH (4.25 ± 0.65 ng/mL; p < 0.05) than in control (2.31 ± 0.20) and PCa group (2.60 ± 0.56). E-selectin, P-selectin and VCAM-1 did not show any significant difference. Higher levels of ICAM-1 were detected in patients with PCa (573.04 ± 52.23) and BPH (564.40 ± 74.67) than in the controls (215.30 ± 11.53 ng/mL; p < 0.05). In local blood samples, IL-6 has been found significantly increased in PCa in comparison with patients with BPH; there was no difference in CD40L, E-selectin, P-selectin, VCAM-1 ed ICAM-1. CONCLUSIONS: Changes in inflammation and endothelial activation markers may be not considered to be of value in discriminating BPH and PCa.

Comparison of oxidative stress & leukocyte activation in patients with severe sepsis & burn injury.

Background & objectives: We evaluated pro- and anti-oxidant disturbances in sepsis and non-sepsis burn patients with systemic inflammatory response syndrome (SIRS). Adhesion molecules and inflammation markers on leukocytes were also analyzed. We hypothesized that oxidative stress and leukocyte activation markers can lead to the severity of sepsis. Methods: In 28 severe sepsis and 27 acute burn injury patients blood samples were collected at admission and 4 days consecutively. Oxidative stress markers: production of reactive oxygen species (ROS), myeloperoxidase, malondialdehyde and endogenous antioxidants: plasma protein sulphydryl groups, reduced glutathione, superoxide dismutase and catalase were measured. Flow cytometry was used to determine CD11a, CD14, CD18, CD49d and CD97 adhesion molecules on leukocytes. Procalcitonin, C-reactive protein, fibrinogen, platelet count and lactate were also analyzed. Results: Pro-oxidant parameters were significantly elevated in sepsis patients at admission, ROS intensity increased in burn patients until the 5th day. Endogenous antioxidant levels except catalase showed increased levels after burn trauma compared to sepsis. Elevated granulocyte activation and suppressed lymphocyte function were found at admission and early activation of granulocytes caused by increasing activation/migration markers in sepsis. Leukocyte adhesion molecule expression confirmed the suppressed lymphocyte and monocyte function in sepsis. Interpretation & conclusions: Severe sepsis is accompanied by oxidative stress and pathological leukocyte endothelial cell interactions. The laboratory parameters used for the evaluation of sepsis and several markers of pro- and antioxidant status were different between sepsis and non-sepsis burn patients. The tendency of changes in these parameters may refer to major oxidative stress in sepsis and developing SIRS in burns.

Soluble cell adhesion molecules and parameters of lipoprotein metabolism in patients with severe burns / Moléculas de adhesión celular soluble y parámetros del metabolismo de la lipoproteína en pacientes con quemaduras severas

BACKGROUND: The role of leukocyte adhesion molecules in patients with burns and their relationship to other parameters of inflammation and lipid metabolism is only recently beginning to be explored. Therefore, we investigated the temporal changes in the levels of soluble cell adhesion molecules and other parameters of inflammation and lipoprotein metabolism in patients with thermal injury. MATERIALS AND METHODS: The serum levels of soluble adhesion molecules, intercellular cell adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), and sE-selectin, C-reactive protein (CRP) and fibrinogen in seven patients with severe burns over a 30- day period were measured to determine the involvement of these factors in the pathophysiology of severe burns. Serum levels of sICAM-1, sVCAM-1 and sE-selectin were determined by ELISA. Furthermore, total cholesterol, high-density lipoprotein cholesterol (HDL chol), low-density lipoprotein cholesterol (LDL chol) and triglycerides (TG) were measured. RESULTS: Blood levels of sICAM-1, sVCAM-1, CRP and fibrinogen increased with maximum values six days after thermal injury. In contrast, serum levels of sE-selectin were elevated two days after thermal injury. The sICAM-1, sVCAM-1 and sE-selectin levels correlated significantly with both the CRP and the fibrinogen levels. Plasma total cholesterol, HDL cholesterol and LDL cholesterol decreased with minimum values four days after thermal injury. Furthermore, an increase of triglyceride levels was observed. CONCLUSION: The observed inflammatory response of soluble cell adhesion molecules could be useful in monitoring endothelial activation immediately following thermal injury. Further studies involving a larger number of patients with burns should help to clarify the extent to which measured parameters, especially the temporal changes of sCAMs, could be relevant in assessing the morbidity of patients with thermal injury.

ANTECEDENTES: El papel de las moléculas de adhesión leucocitaria en pacientes con quemaduras y su relación con otros parámetros de inflamación y metabolismo de lípidos ha comenzado a ser explorados sólo recientemente. Por lo tanto, investigamos los cambios temporales en los niveles de las moléculas de adhesión celular solubles y otros parámetros de inflamación y metabolismo de las lipoproteínas en pacientes con daños térmicos. MATERIALES Y MÉTODOS: Los niveles de suero de las moléculas de adhesión solubles, las moléculas 1 de adhesión intracelular (sICAM-1), las moléculas 1 de adhesión celular vascular (sVCAM-1) y sE-selectina, la proteína reactiva C (CRP), y el fibrinógeno en siete pacientes con quemaduras severas en un período de 30 días, fueron medidas a fin de determinar la participación de estos factores en la patofisiología de las quemaduras severas. Los niveles séricos de sICAM-1, sVCAM-1 y sE-selectina fueron determinados mediante ELISA. Además, se midieron el colesterol total, el colesterol de lipoproteína de alta densidad (HDL col), el colesterol de lipoproteína de baja densidad (LDL col), y los triglicéridos. RESULTADOS: Los niveles de sangre de sICAM-1, sVCAM-1, CRP y fibrinógeno aumentaron a valores máximos, seis días después del daño térmico. Los niveles de sICAM-1, sVCAM-1 y sE-selectina tuvieron una correlación significativa tanto con la CRP como con los niveles de fibrinógeno. El colesterol total de plasma, el colesterol HDL y el colesterol LDL disminuyeron a valores mínimos cuatro días después del daño térmico. Además, se observó un aumento en los niveles de triglicéridos. CONCLUSIÓN: La respuesta inflamatoria observada de las moléculas de adhesión celular soluble puede ser útil para monitorear la activación endotelial inmediatamente luego del daño térmico. Estudios ulteriores que comprendan un gran número de pacientes con quemaduras deben ayudar a aclarar hasta que punto los parámetros medidos, especialmente los cambios temporales de sCAMs, pudieran ser relevantes a la hora de evaluar la morbilidad de los pacientes con heridas térmicas.

Marcadores pro y antiinflamatorios en la enfermedad arterial coronaria y el síndrome isquémico coronario agudo / Pro-inflammatory and anti-inflammatory markers in coronary artery disease and acute ischemic coronary syndrome

Inflammation plays an important role in the development of atherosclerotic lesions, affecting several stages of the atheroma's development going from the initial leukocyte recruitment to the eventual rupture of the unstable atherosclerotic plaque. The inflammatory reactions within coronary atherosclerotic plaques influence the clinical outcome of acute coronary syndromes and coronary artery disease. Recent studies suggest that inflammation markers may reflect different aspects of the atherothrombotic process in relation to the stages of acute coronary syndrome. These markers play an important role in the risk of developing coronary artery disease, and may correlate with its severity. Some cytokines, acute phase proteins, acute phase reactants proteins, and adhesion molecules released from the inflammatory cells may reflect the inflammatory process in atherosclerotic plaques. However, it remains to be determined whether these pro- and anti-inflammation markers may confer risk or protection for cardiovascular disease, or simply reflect the underlying disease process. The analysis of the markers may be useful for the development of new strategies for coronary disease prevention and treatment. Therefore, we need a well-designed evaluation of these markers before their use in the clinical practice.

Primeiro escore de risco inflamatório das endopróteses de aorta / First inflammatory risk score for aortic endoprostheses

OBJETIVO: Propor um escore de risco inflamatório para tratamento endovascular dos aneurismas da aorta. MÉTODOS: Vinte e cinco pacientes foram seguidos do período pré-operatório até 3º mês de pós-operatório (1 hora, 6 horas, 24 horas, 48 horas, 7 dias, 1 mês, 2 meses e 3 meses). Variáveis inflamatórias avaliadas foram proteína C reativa, velocidade de hemossedimentação, interleucinas (IL-6, IL8), fator de necrose tumoral alfa, L-selectina, molécula de adesão intercelular (ICAM-1), transfusão de hemáceas, volume de cristalóide, volume de contraste, material da prótese, número de próteses, contagem total de leucócitos e linfócitos. O teste de Spearman apontou as variáveis candidatas ao maior risco inflamatório, segundo P < 20 por cento. A regressão logística apontou variáveis selecionáveis para escore final segundo P < 10 por cento. A análise da curva ROC revelou valores de corte para variáveis selecionadas pela regressão logística. RESULTADOS: Variáveis apresentadas pelo teste de Spearman foram: volume de cristalóide (P = 0,04), material da prótese (P = 0,04), volume de contraste (P=0,02), IL-8 préoperatória (P= 0,10), ICAM-1 1 mês (P=0,03) e L-selectina 1 mês (P = 0,06). A regressão logística revelou que os valores do volume de cristalóide e IL-8 pré-operatória são primordiais para constituição do escore de risco inflamatório para tratamento endovascular dos aneurismas da aorta. O escore de risco seria dividido em três categorias (leve, moderado e grave), com base em intervalos numéricos das duas variáveis selecionadas e as categorias seriam correlacionadas com achados clínicos CONCLUSÃ: Volume de cristalóide e IL-8 pré-operatória são variáveis que poderiam contribuir para categorizar risco inflamatório e, desse modo, ter um papel prognóstico no tratamento endovascular dos aneurismas da aorta.

OBJECTIVE: To purpose an inflammatory risk score for aortic aneurysm endovascular treatment. METHODS: Twenty-five patients were followed-up from preoperative period to third month postoperatively (1-hour, 6-hour, 24-hour, 48-hour, 7-day, 1-month, 2- month and 3month). Inflammatory variables were C-reactive protein, hemosedimentation velocity, interleukins (IL-6, IL-8), tumor necrosis factor-Alpha, L-selectin, intercellular adhesion molecule (ICAM-1), red blood cells transfusion, volume of crystalloid, volume of contrast, type of endoprosthesis, number of endoprostheses, total count of leukocytes and lymphocytes. Spearman test defined the variables considered as candidates to higher inflammatory risk based on P < 20 percent. Logistic regression defined the variables considered as selected for final score based on P < 10 percent. ROC curve analysis revealed the cut-off values for variables selected by logistic regression. RESULTS: Variables defined by Spearman test were: volume of crystalloid (P=0.04), type of endoprosthesis (P=0.04), volume of contrast (P=0.02), preoperative IL-8 (P = 0.10), 1 - month ICAM-1 (P=0.03) and 1-month L-selectin (P=0.06). Logistic regression revealed that volume of crystalloid and preoperative IL-8 values are relevant for composition of inflammatory risk score for aortic aneurysm endovascular treatment. Risk score would be divided into three categories (mild, moderate and severe) based on numeric intervals of these two variables and the categories would be correlated to clinical findings. CONCLUSION: Volume of crystalloid and preoperative IL-8 are variables that might contribute to categorize inflammatory risk and thereby might play a prognostic role for aortic aneurysm endovascular treatment.

Anemia falciforme: polimorfismos gênios em moléculas de adesão (VCAM-1 e ICAM-1), TNF-ALFA-, IL-8 e alterações fonotípicas / Sickle cell anemia: polymorphisms geniuses in molecules of accession (VCAM-1 and ICAM-1), TNF-ALPHA-, IL-8 and amendments fonotípicas

A hemoglobina S é resultado da mutação pontual A>T no sexto códon do gene beta da globina, conduzindo à substituição do ácido glutâmico pela valina na cadeia da globina beta. A anemia falciforme apresenta heterogeneidade clinica, com a gravidade variável atribuída ao pleiotropismo gênico dos pacientes. Logo, alguns pacientes apresentam alterações gênicas variadas que podem refletir na melhora ou não do fenótipo apresentado. O estudo investigou polimorfismos gênicos em moléculas de adesão (VCAM-1 e ICAM-1) e citocinas (TNF-alfa e IL-8) correlacionando-os aos níveis séricos das citocinas, parâmetros hematológicos e manifestações clinicas apresentadas em um grupo de pacientes pediátricos com anemia falciforme em Salvador-Bahia. No estudo foram investigados 125 pacientes pediátricos com anemia falciforme e 212 indivíduos sadios da população de Salvador. Os polimorfismos gênicos foram investigados por PCR-RFLP. Os níveis séricos das citocinas foram avaliados por ELlSA. As análises estatísticas foram realizadas pelo programa EPI-INFO versão 6.04 e a significância foi estabelecida para p < 0,05. Do total de 125 pacientes analisados, 27 (22 por cento) foram heterozigotos para o polimorfismo -833 na região promotora do gene da VCAM-1; 15 (12 por cento) foram heterozigotos para o polimorfismo 1238 no gene da VCAM-1; 50 (40 por cento) foram heterozigotos e oito (2 por cento) homozigotos para o polimorfismo 469 no gene da ICAM-1; 30 (24 por cento) foram heterozigotos e dois (2 por cento) homozigotos para o polimorfismo -308 na região promotora do gene do TNF-alfa; 66(53 por cento) foram heterozigotos e 43 (34 por cento) homozigotos para o polimorfismo -251 na região promotora do gene da IL-8. Nossos resultados demonstraram que não houve associação estatística entre os polimorfismos -308 na região promotora do gene do TNF-alfa e -251 na região promotora do gene da IL-8 e os níveis séricos das citocinas...

Levels of soluble adhesion molecule vcam-1 and icam-1 in the plasma of chronic transfused children with sickle cell disease

Increased adhesive events between the blood vessel endothelium and red and white cells play a central role in the initiation of vasoocclusive crisis. We examined endothelial functions and serum levels of inflammatory mediators in transfusion-dependent patients with sickle cell disease in stable asymptomatic stage and on crisis. The study population consisted of 40 patients with sickle cell disease [SCD] aged from 5 years to 13 years and 35 healthy normal individual with matched age and sex as control group .Serum levels of vascular cell adhesive molecules [sVCAM-1] and intercellular adhesive molecule [sICAM-1] with serum level of interleukin 6 [IL6] were determined with Enzyme -Link Immunosorbent assay [ELISA]. Asymptomatic patients with sickle cell diseases had higher sVCAM-1 levels compared to normal controls [p<0.001]. Their levels were further elevated during acute episodes. Levels were significantly lower in chronic transfused child patients compared to acute crisis p= [<0.05].The reduction of adhesive molecule levels observed in our transfused SCD patients offers insight into the mechanism of the protective effect of transfusion against acute crisis especially painful and anemic crisis. SVCAM-1 and sICAM-1 levels inversely correlated with fetal hemoglobin in SCD patients. In conclusion, adhesive molecule expression uad cytokine production may also play a role in the disease outcome

Marcadores inflamatórios intracoronarianos após intervenções coronarianas percutâneas / Intracoronary inflammatory markers after percutaneous coronary interventions

OBJETIVO: Analisar a liberação intracoronariana de marcadores inflamatórios (MI) após intervenções coronarianas percutâneas (ICP) e comparar suas concentrações com relação ao tipo de ICP utilizada (rotablator vs angioplastia por balão). MÉTODOS: Foram randomizados 22 pacientes com média de idade de 60±11,9 anos, 12 do sexo masculino, portadores de síndromes coronarianas estáveis, submetidos ao tratamento eletivo de uma única lesão coronariana utilizando rotablator (N=11) ou pré-dilatação por balão (N=11) para implante de stents. As amostras foram colhidas na raiz da aorta e no seio coronariano, imediatamente antes e 15 minutos após as intervenções. Todas as dosagens foram feitas antes do implante do stent, sendo analisadas as citocinas TNF-a, IL-6 e IL-1 e as moléculas de adesão solúveis ICAM-1, E-selectina e P-selectina, utilizando o método ELISA. RESULTADOS: As concentrações de TNF-a e IL-6 aumentaram após as ICP, passando respectivamente de 9,5±1,5 pg/ml para 9,9±1,8 pg/ml (p=0,017) e de 6,0±2,4 pg/ml para 6,9±3,0 pg/ml (p<0,001). Não houve mudança significativa na expressão de IL-1, ICAM-1 e P-selectina, observando-se diminuição nas concentrações de E-selectina após os procedimentos (52,0±17,5 ng/ml para 49,3±18,7 ng/ml; p=0,009). Não houve diferença significativa entre as concentrações dos MI após as ICP, com relação ao tipo de procedimento utilizado. CONCLUSAO: No período precoce, pós-intervenções coronarianas percutâneas, observou-se aumento das concentrações intracoronárias de TNF-a e IL-6 e ausência de diferença significativa entre as concentrações dos marcadores inflamatórios liberados na circulação coronariana por rotablator e pela angioplastia com balão.

Moleculas de adhesion: su papel en la fisiopatologia cardiovascular / Adhesion molecules: their role in cardiovascular physiopathology

Las moléculas de adhesión son receptores de menbrana que participan en diversas funciones vinculadas al tráfico celular, a las interacciones célula-célula y célula-matriz extracelular. Tres grupos destas moléculas, conocidas como "adhesinas", están relacionados con la enfermedad cadiovascular: integrinas, selectinas y superfamilia de inminoglobulinas. Intervienen en los fenómenos de activación y desifunción endotelial y se vinculan a la patogenia de la enfermedad coronaria, la injuria por reperfusión, el rechazo del corazón transplantado, la miocarditis, la miocardiopatía hipertrófica, etc. Se asocian también con el mecanismo de acción de las estatinas. El dosaje de los niveles séricos de las moléculas de adhesión tiene valor diagnóstico y predictivo de diversas enfermedades cardiovasculares. Esta revisión enfoca las variadas funciones de las adhesinas y se orienta sobre diversas posibilidades terapéuticas derivadas de su conocimiento.

Maternal Serum Levels of VCAM-1, ICAM-1 and E-selectin in Preeclampsia

Endothelial dysfunction is thought to be a central pathogenic feature in preeclampsia on the basis of elevated adhesion molecules. The aim of the present study was to compare the levels of soluble vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1) and E-selectin (sE-selectin) in sera of normal and preeclamptic pregnancies. We studied the serum levels of sVCAM-1, sICAM-1 and sE-selectin in normal pregnant women (n=63), mild preeclampsia (n=33) and severe preeclampsia (n=82). Concentrations of soluble adhesion molecules were determined with enzyme-linked immunoassay (ELISA). Serum concentrations of sVCAM-1 were significantly higher in both mild (p=0.004) and severe preeclampsia (p=0.000) than normal pregnancy. There were also significant differences in sVCAM-1 levels between mild and severe preeclampsia (p=0.002). sICAM-1 levels of severe preeclampsia were statistically different from those of normal pregnancy (p=0.038). Levels of sE-selectin were elevated in both mild (p=0.011) and severe preeclampsia (p=0.000) compared to normal pregnancy, but no statistical difference between the mild and severe preeclampsia (p=0.345). These results suggest that all three soluble adhesion molecules are increased in severe preeclampsia, and sVCAM-1 among them may be useful in predicting the severity of preeclampsia.

Células mononucleares de sangue de cordão umbilical e de sangue periférico estimulado com fator de crescimento granulocítico (G-CSF): análise da proliferação e de apoptose in vitro / Mononuclear cells of umbilical cord blood and of granulocyte colony-stimulating factor: analyses of proliferation and apoptosis in vitro

Células mononucleares de sangue de cordão umbilical (SCU) e sangue periférico mobilizado (SPM) com G-CSF, foram cultivadas in vitro com citocinas, na presença ou não de estroma de medula óssea. Os objetivos foram avaliar a capacidade proliferativa de células progenitoras, a ocorrência de apoptose e expressão de integrina. Nas culturas sem estroma, a celularidade aumentou 5 vezes (SCU) e não se alterou nas de SPM. O total de células CD34+ caiu em ambas culturas. Com estroma, o total de células nucleadas aumentou 7 vezes (SCU) e 2,3 vezes (SPM). O total de células CD34+ permaneceu o mesmo. A apoptose foi menor nas culturas de SCU. A expressão de integrina caiu, na população de células CD34+ e de CD45+ / Mononuclear cells from umbilical cord blood (UCB) and G-CSF mobilized peripheral blood (MPB), were cultured in vitro, in the presence of cytokines, with or without bone marrow stroma. The aims were to evaluate the proliferative response of progenitor cells, occurrence of apoptosis and expression of adhesion molecule. In cultures without stroma, cellularity increased 5-fold for UCB, but has not changed for MPB. The number of CD34+ cells has dropped in both culture. With stroma, total nucleated cells had a 7-fold increse (UCB) and a 2,3-fold (MBP), however, CD34+ cells number has not changed. Apoptosis was lower in UCB culture. The expression of integrin decreased, in the...

ICAM-1 and L-selectins: the cell adhesion molecules among children with nephrotic syndrome

In this study, intercellular adhesion molecules [ICAM-1] and L-selectin were described in sera from 36 children suffering from idiopathic nephrotic syndrome by using ELISA. They were classified into three groups: Group I, 26 patients with minimal change nephritic syndrome [MCNS]; group II, 10 cases of non-minimal change nephrotic syndrome [MCNS] [6 cases of mesangioproliferative and 4 cases of focal segmental glomerulosclerosis] and group III,15 healthy children were enrolled to serve as controls. Patients within group I were reexamined according to the disease activity and steroid therapy. The study concluded that the elevation in serum ICAM-1 and L-selectin in MCNS and non-MCNS groups compared with the healthy controls could provide the basis for disturbance in T cell function in patients with nephrosis, suggesting that the disease is mediated by immunologic mechanisms disturbing the cellular immunity

Anti-endothelial cell antibodies and soluble adhesion molecules in rheumatoid arthritis complicated with peripheral neuropathy

To examine whether levels of anti-endothelial cell antibodies [AECA], soluble vascular cell adhesion molecule-1 [sVCAM-1 and E-selectin were elevated in rheumatoid arthritis [RA] patients complicated with peripheral neuropathy [PN] as compared to RA patients without neuropathy and healthy controls. Also, to correlate these criteria with the parameters of disease activity. Levels of AECA, sVCAM-1 and E-selectin were determined with ELISA in 30 RA patients with PN, 30 RA patients without neuropathy and 25 healthy controls. RA patients with PN had significantly higher levels of AECA, sVCAM-1 and E-selectin than RA patients without neuropathy and healthy controls. Those three markers significantly correlated with the clinical and laboratory parameters of disease activity. Serum levels of AECA, sVCAM-1 and E-selectin proved to be higher in RA patients with PN than in RA patients without neuropathy. This reflects increased endothelial cell activation in RA patients complicated with neuropathy

High resolution ultrasonography in assessment of rheumatoid knee synovitis: correlation with clinical and laboratory parameters

The formation of synovial pannus is an early event in the course of rheumatoid arthritis [RA] and could be seen before destruction of the cartilage and bone. Thus, its evaluation is of great benefit in the treatment and follow-up of clinical remission. The aim of this study was to investigate the presence of synovial pannus in the knee of RA patients with high-resolution ultrasonography and correlate the finding with the clinical and laboratory parameters of the disease. Thirty patients suffering from RA diagnosed according to the American College of Rheumatology [ACR] criteria together with 10 apparently healthy volunteers were included in the study. Both patients and controls were subjected to proper history taking and clinical examination including disease activity scoring [Mallya and Mace 1981] and functional assessment [Steinbrocker criteria, 1949] together with high resolution ultrasonography of the knee. Soluble adhesion molecules [SICAM-1 and E selectin] in the serum as well as serum and synovial L1F were also done. A high statistical significant difference was found in all laboratory and clinical findings between the patients group and control group including SIC AM-1, SE-selectin, serum and synovial LIF. Serum and synovial LIF correlated significantly with activity scoring [r- 0.8] and, functional status [r= 0.7]. However, SICAM-1 and SE-selectin correlated with activity scoring only [r= 0.48, r= 0.49 respectively]. Ultrasonographic findings were detected in the majority of the patients with statistically significant difference if compared with the control group. Synovial thickening correlated significantly with disease duration [r- 0.49], functional status [r- 0.58] and synovial LIF [r- 0.59]. Effusion showed a significant correlation with activity scoring [r= 0.5], SICAM-1 [r= 0.42] and synovial LIF [r= 0.59] while cartilage destruction correlated with disease duration [r= 0.51] and serum and synovial LIF [r= 0.53 and 0.65 respectively]. Soluble adhesion molecules may be an additional marker for disease activity while LIF may be an indicator of the severity of the disease. HRUS can evaluate the pannus formation in a trial to assess disease activity and the degree of severity to aid in therapeutic intervention and follow-up for clinical remission

Circulating adhesion molecules in orthotopic liver transplantation: relation to clinical course

Intercellular adhesion molecules [ICAMs] constitute an integral part of the immune reactions in various clinical conditions. Soluble forms shed or released from effector cells retain ligand-binding activity and their measurement in body fluids has proved as useful markers of cellular and endothelial reactivity. In this work, circulating soluble intercellular adhesion molecule-1 [sICAM-1], soluble vascular cell adhesion molecule [sVCAM-1], soluble E and P-selectins [sE- and sP-selectins] were measured by enzyme immuno-assay [EIA] in the serum of 27 liver transplant recipients who received cadaveric grafts within the previous 13 years and who were showing different clinical courses. 13 patients were having stable graft function [Stable group] and 14 showing evidence of chronic rejection +/- viral pathology [Unstable group]. 12 patients with hepatitis C virus [HCV] cirrhosis still on the waiting list for liver transplantation were also included [Pre-transplant group], in addition to 15 healthy subjects matched for age and sex [Control group]. A significant increase in sICAMs was noted in all patient groups as compared to controls except those stable non-viral cases who showed sICAM levels comparable to the control subjects. Patients transplanted for non-viral aetiology had their levels markedly lower than viral cases, whether stable or unstable. Stable cases showing viral recurrence had their sICAM levels comparable to the pre-transplanted cases with an insignificant increase in the unstable group. We could conclude that sICAM levels can be used to monitor graft integrity in the non-viral cases but their use in patients transplanted for viral causes would not be justified