Serum tissue factor as a biomarker for renal clear cell carcinoma

ABSTRACT Purpose to determine the usefulness of serum TF as a potential marker for patients with clear cell RCC. Materials and Methods prospective study of 30 patients with clear cell RCC submitted to nephrectomy and 16 controls without clear cell RCC treated surgically for other conditions. TF is a endothelium marker that was correlated with worse prognosis in a variety of solid tumors including RCC. Serum TF was collected before surgery at the operating room and in the postoperative setting after at least four weeks. Serum samples were analyzed with a commercial ELISA kit for human TF (R&D Systems®). Results Mean preoperative serum TF levels in clear cell RCC patients and in controls were 66.8 pg/dL and 28.4 pg/dL, respectively (p<0.001). Mean postoperative serum TF levels in clear cell RCC patients were 26.3 pg/dL. In all patients with clear cell RCC postoperative serum levels of TF were lower, with a mean reduction of 41.6 pg/dL in the postoperative setting (p<0.001). Linear regression revealed that tumor size was correlated with the postoperative reduction of serum TF levels (p=0.037). Conclusions We have shown a 3-fold reduction in the median preoperative serum levels of TF in patients with clear cell RCC after surgery. We have also shown a difference of the same magnitude in the serum levels of TF compared with those of a control group of patients with benign diseases. TF appears to be a useful serum marker for the presence of clear cell RCC. Further studies are needed to validate these findings.

Effects of hyaluronic acid on bleeding following third molar extraction

Abstract Objective To explore the effects of hyaluronic acid (HA) on bleeding and associated outcomes after third molar extraction. Methods Forty patients who had undergone molar extraction were randomly divided into two groups; 0.8% (w/v) HA was applied to the HA group (n=20) whereas a control group (n=20) was not treated. Salivary and gingival tissue factor (TF) levels, bleeding time, maximum interincisal opening (MIO), pain scored on a visual analog scale (VAS), and the swelling extent were compared between the two groups. Results HA did not significantly affect gingival TF levels. Salivary TF levels increased significantly 1 week after HA application but not in the control group. Neither the VAS pain level nor MIO differed significantly between the two groups. The swelling extent on day 3 and the bleeding time were greater in the HA group than in the control group. Conclusions Local injection of HA at 0.8% prolonged the bleeding time, and increased hemorrhage and swelling in the early postoperative period after third molar extractions.

The involvement of endothelial mediators in leprosy

Leprosy is a chronic infectious disease that requires better understanding since it continues to be a significant health problem in many parts of the world. Leprosy reactions are acute inflammatory episodes regarded as the central etiology of nerve damage in the disease. The activation of endothelium is a relevant phenomenon to be investigated in leprosy reactions. The present study evaluated the expression of endothelial factors in skin lesions and serum samples of leprosy patients. Immunohistochemical analysis of skin samples and serum measurements of VCAM-1, VEGF, tissue factor and thrombomodulin were performed in 77 leprosy patients and 12 controls. We observed significant increase of VCAM-1 circulating levels in non-reactional leprosy (p = 0.0009). The immunostaining of VEGF and tissue factor was higher in endothelium of non-reactional leprosy (p = 0.02 for both) than healthy controls. Patients with type 1 reaction presented increased thrombomodulin serum levels, compared with non-reactional leprosy (p = 0.02). In type 2 reaction, no significant modifications were observed for the endothelial factors investigated. The anti-inflammatory and antimicrobial activities of the endotfhelial factors may play key-roles in the pathogenesis of leprosy and should be enrolled in studies focusing on alternative targets to improve the management of leprosy and its reactions.

Increased expression of tissue factor and protease-activated receptor-1 does not correlate with thrombosis in human lung adenocarcinoma

A correlation between cancer and hypercoagulability has been described for more than a century. Patients with cancer are at increased risk for thrombotic complications and the clotting initiator protein, tissue factor (TF), is possibly involved in this process. Moreover, TF may promote angiogenesis and tumor growth. In addition to TF, thrombin seems to play a relevant role in tumor biology, mainly through activation of protease-activated receptor-1 (PAR-1). In the present study, we prospectively studied 39 lung adenocarcinoma patients in relation to the tumor expression levels of TF and PAR-1 and their correlation with thrombosis outcome and survival. Immunohistochemical analysis showed TF positivity in 22 patients (56 percent), most of them in advanced stages (III and IV). Expression of PAR-1 was found in 15 patients (39 percent), most of them also in advanced stages (III and IV). Remarkably, no correlation was observed between the expression of TF or PAR-1 and risk for thrombosis development. On the other hand, patients who were positive for TF or PAR-1 tended to have decreased long-term survival. We conclude that immunolocalization of either TF or PAR-1 in lung adenocarcinoma may predict a poor prognosis although lacking correlation with thrombosis outcome.

Surface and total tissue factor activity of endothelial cells.

With a technic that was developed by us, we found that normal human umbilical vein endothelial cells (HUVEC) in culture characteristically had very little tissue factor (TF) activity either on the surface or in the cells which had been disrupted. In the presence of endotoxin (E. coli O26:B6), a trigger for thrombosis in septicemic patients, we could not detect an increased TF activity of HUVEC on its surface. However, an increase in TF (total TF) was detected after disruption of the cells. The increase in total TF was dose-dependent. Endotoxin at the concentration of 10 micrograms/ml caused around 5 fold increase in total TF activity compared to that of HUVEC in the absence of endotoxin.

A simple and quantitative method for the determination of tissue factor.

Tissue factor (TF), a potent initiator of the extrinsic coagulation pathway, is believed to have a critical role in thrombogenesis and haemostasis. To elucidate the role of TF in the development of various syndrome, we developed a quantitative assay method for the determination of TF using FIX complex (Profilnine) and the synthetic chromogenic substrate S-2238, all of which are commercially available. The method is simple, very sensitive, good linearity and applicable to the tissue culture plate, indicating its promising usage for the quantitation of TF activity of cells.

Efeito da infecção por Actinobacillus pleuropneumoniae nos mecanismos da coagulação do sangue de leitões / Effect of Actinobacillus pleuropneumoniae infection on pigs' blood coagulation system

O presente trabalho apresenta os resultados do estudo do efeito da infecção causada por Actínobacíllus pleuropneumoníae no sistema da coagulação do sangue de leitões. Vinte e cinco leitões desmamados, isentos de organismos patogênicos específicos, foram separados, ao acaso, em dois grupos. Dez leitões foram infectados com 5x1 06 CFU de A. pleuropneumoníae sorotipo 1, e quinze foram usados como controle negativo. O tempo parcial ativado de tromboplastina aumentou enquanto que o tempo da protrombina, expressado em porcentagem, diminuiu. As alterações observadas no tempo de trombina e na quantidade de fibrinogênio estão relacionadas com a formação de fibrina no processo de coagulação. Admitimos que estas observações estejam ligadas ao consumo de fatores de coagulação do sangue nos caminhos intrínsecos, extrínsecos e comuns. Assim, a hemorragia pulmonar e a formação de coágulos, que são características da fase aguda dessa doença, podem ser explicadas.

The effect of Actinobacillus pleuropneumoniae infection on pigs' blood coagulation system was studied. Twenty five specific pathogen free weaned piglets were randomly assorted into two groups. Ten of the piglets were infected with 5x10 6 CFU of A. pleuropneumoniaeserotype 1, and 15 used as negative contrais. The prothrombin time, expressed as percentage, decreased. The activated partial thromboplastin time increased and the thrombin time decreased. Concentrations of fibrinogen increased during the trial. These observations were consistent with consumptions of blood coagulation factors in the intrinsic, extrinsic, and common pathways of blood coagulation, producing coagulability. Therefore intrapulmonary haemorrhage and clot formation may be observed in the lungs of piglets infected with A. pleuropneumoniae.

La importancia del cociente calibrado internacional como índice en la evaluación de la anticoagulación oral / Importance of the International Calibrated Rate (INR) as index in oral anticoagulation evaluation

En este trabajo se presenta el cociente calibrado internacional (CCI), índice que es el utilizado hoy en día para evaluar el tratamiento anticoagulante por vía oral. Se indica la metodología para obtenerlo a partir de una tromboplastina nacional con base en una tromboplastina de referencias, siguiendo las normas y recomendaciones de la Organización Mundial de la Salud

Estudio de la vida útil de la tromboplastina de placenta humana liofilizada / Study of the useful life of tromboplastin from lyophilized human placenta

Se realizó un estudio durante 2 años de las variaciones que experimentan la actividad biológica y algunos parámetros químicos como: niveles de proteínas, fosfolípidos y malonaldehído de la tromboplastina placentaria humana liofilizada, con la finalidad de determinar la temperatura óptima de almacenamiento. Se obtuvo como resultado que tanto el tiempo de protrombina como el de coagulación se mantenían estables cuando los lotes eran almacenados a temperatura de congelación (-20-C), que el tiempo de protrombina variaba dentro del rango permisible cuando los lotes se mantenían a temperatura de refrigeración (2-8-C), mientras que cuando se almacenaban a temperatura ambiente la actividad biológica ofrecía resultados muy variables. El estudio de los parámetros químicos tales como: proteínas, fosfolípidos y malonaldehídos reveló que la proteína variaba dentro de los grupos, el malonaldehído aumentaba la temperatura, mientras que el fosfolípido disminuía

Tiempo de tromboplastina parcial activado y tiempo de trombina en el control de la heparinoterapia: comparacion de diferentes tromboplastinas; estudio in vitro / Partial thromboplastin time activated and thrombin time in control of heparin-therapy: comparison of different thromboplastins: in vitro study

Se estudio in vitro la sensibilidad de las diferentes tromboplastinas comerciales usadas en Colombia, con el tiempo de tromboplastina parcial activado, usando un "pool" de plasmas normales con diferentes concentraciones de heparina (0,2 a 0.6 unidades por ml). Igualmente se midio el efecto heparinico por medio del tiempo de trombina. La tromboplastina mas sensible fue el Pathromtin y la menos sensible el Actin. Ambas con diferencias estadisticamente significativas (p<0.001). E1TT demuestra gran sensibilidad, pocos factores inciden sobre el y permite determinar las concentraciones de heparina plasmaticas. Los diferentes laboratorios deberan establecer la sensibilidad de las diferentes tromboplastinas que utilizan para proporcionar una monitoria efectiva durante el tratamiento anticoagulante con heparina.

Propriedades procoagulantes del líquido amniótico: I. El tiempo de aceleración de tromboplastina en líquido amniótico a través del embarazo normal; sus perspectivas clínicas / Procoagulant properties of a amniotic fluid: I. Thromboplastin acceleration time in amniotic fluid through normal pregnancy; its clinical perspectives

Con el propósito de determinar las propiedades procoagulantes del líquido amniótico a través del embarazo, se analizó en 245 líquidos amnióticos de embarazos normales a diferentes edades gestacionales, el tiempo de aceleración de tromboplastina (TAT en L.A.). Se encontró que existe una aceleración progresiva de este parámetro conforme avanza el embarazo, teniendo un índice de correleción altamente significativo desde el punto de vista estadístico, así como desviación estándar, error estándar y dispersión pequeños. Se concluye que existen amplias perspectivas de uso clínico de este procedimiento y que es muy aplicable en nuestro medio aun en centros hospitalarios de escasos recursos, por ser una técnica sencilha, rápida, barata y requerir una cantidad mínima de líquido amniótico para su práctica