An increase in the cerebral infarction area during fatigue is mediated by il-6 through an induction of fibrinogen synthesis

OBJECTIVES: Our study aimed to investigate the impact of fatigue on the severity of stroke and to explore the underlying mechanisms. METHODS: Fatigued male rats underwent middle cerebral artery occlusion and the infarcted brain area was determined. Then, coagulation parameters were assessed in the fatigued group and a control group. In addition, the level of fibrinogen was determined in rats deprived of sleep for various numbers of days. To study whether interleukin-6 was involved in fibrinogen synthesis during fatigue, we also measured levels of interleukin-6 in rats deprived of sleep for various numbers of days. Furthermore, brain injury by middle cerebral artery occlusion was measured in wild-type mice, interleukin-6-/- mice and wild-type mice treated with bezafibrate. RESULTS: More severe cerebral infarction was observed in the fatigued rats, resulting in an infarct ratio of 23.4%. The infarct ratio was significantly increased in the fatigued rats compared with that in the control group (8%, p<0.05). The level of fibrinogen was increased significantly in the fatigued rats compared with that in the control group. In addition, a marked reduction in fibrinogen level was observed in the fatigued interleukin-6-/- mice compared to their wild-type counterparts, whereas no difference was observed between fatigued wild-type mice and interleukin-6-/- rats treated with recombinant human interleukin-6. The reduction in brain injury due to middle cerebral artery occlusion during fatigue was observed in interleukin-6-/- mice and wild-type mice treated with bezafibrate. CONCLUSION: Fatigue could increase stroke severity and was associated with the interleukin-6-induced expression of fibrinogen. .

Marcadores de inflamación y disfunción endotelial en niños con diabetes tipo 1 / Inflammation markers and endothelial disfunction in children with type 1 diabetes

Se ha hallado un estado inflamatorio subclínico ha sido informado en la fase temprana de la diabetes, el cual incrementa los niveles séricos de citoquinas que inducen la síntesis de proteínas de fase aguda como la proteína C reactiva (PCR) y el fibrinógeno (Fg), y estimula la expresión endotelial de moléculas de adhesión. Se estudiaron 30 pacientes (15 varones y 15 mujeres) con diabetes tipo 1 (DT1), de 11.8 ± 2.1 años de edad y 3.9 ± 3.2 años de evolución de la enfermedad, sin complicaciones vasculares. Se realizó recuento de leucocitos, velocidad de sedimentación globular (VSG), glucemia en ayunas, hemoglobina glicosilada (HbA1c), Fg, PCR ultrasensible (uPCR), determinación E-selectina soluble (sE-S), molécula de adhesión vascular celular 1 (VCAM-1) y microalbuminuria. Se encontraron niveles aumentados de uPCR, sE-S y VCAM-1 en los pacientes diabéticos comparados con el grupo control [0.60 (0.30-1.25) vs. 0.20 (0.20-0.65) mg/l, p = 0.013], [108 (60-150) vs. 68 (56-82) ng/ml, p = 0.0031] y [750 (708-826) vs. 721 (674-751) ng/ml, p = 0.039] respectivamente. Al agrupar a los diabéticos de acuerdo a la duración de la enfermedad (= 3 y > de 3 años), los valores de uPCR fueron mayores en el segundo grupo. La uPCR se correlacionó con sE-S (r = 0.44, p = 0.03) y con VCAM-1 (r = 0.49, p = 0.02). Estos resultados sugieren la presencia de un estado proinflamatorio y de activación endotelial estrechamente asociados en la DT1.

A subclinical inflammation state was detected in the early step of diabetes, which increases the serum levels of cytokines that induce acute-phase protein synthesis as C-reactive protein (PCR) and fibrinogen (Fg), stimulating the endothelial disfunction of adhesion molecules. Thirty patients (15 boys, 15 girls) with type 1 diabetes (DT1), without vascular complications, were studied. Their mean age and duration of diabetes were 11.8 ± 2.1 and 3.9 ± 3.2 years, respectively. The laboratory parameters evaluated were: blood leukocytes count, globular sedimentation velocity, fasting glycemia, glycosylated hemoglobin (HbA1c), high sensitivity PCR (uPCR), plasma soluble E-selectin (sE-S), sVCAM-1 and microalbuminuria. Increased levels of uPCR, sE-S and VCAM-1 were found, compared with the control group control [0.60 (0.30-1.25) vs. 0.20 (0.20-0.65) mg/l, p = 0.013], [108 (60- 150) vs. 68 (56-82) ng/ml, p = 0.0031] y [750 (708-826) vs. 721 (674-751) ng/ml, p = 0.039] respectively. When diabetic patients were grouped according to duration of disease (= 3 and > de 3 years), uPCR values were higher in the second group. uPCR levels were better correlated with sE-S (r = 0.44, p = 0.03) and VCAM-1 (r = 0.49, p = 0.02). These results suggest the presence of pro-inflammatory and endothelial activation states, which are strongly associated with DT1.

Homocysteine and Fibrinogen Changes with L-thyroxine in Subclinical Hypothyroid Patients

The aim of the present study was to evaluate plasma total homocysteine (Hcys) and serum fibrinogen concentrations in subclinical hypothyroid (SH) and overt hypothyroid patients before and after L-thyroxine (LT4) replacement and to compare them in euthyroid subjects. Fifteen SH and 20 hypothyroid premenopausal women were recruited in the study. We measured fasting plasma levels of Hcys and serum levels of free thyroxine (fT4), free triiodothyronine (fT3), thyrotropin (TSH), folate, vitamin B12, fibrinogen, renal functions, and lipid profiles in patients with SH and overt hypothyroid patients before and after LT4 treatment. Eleven healthy women were included in the study as a control group. Pretreatment Hcys levels were similar in SH and control subjects, whereas mean fibrinogen level of SH patients was higher than that of control subjects (p<0.05). Baseline Hcys (p<0.01) and fibrinogen (p<0.001) levels of the overt hypothyroid patients were significantly higher than those of the healthy subjects, and the pretreatment Hcys levels decreased with LT4 treatment (p<0.001). In conclusion, our data support that SH is not associated with hyperhomocysteinemia and Hcys does not appear to contribute to the increased risk for atherosclerotic disease in patients with SH.

Fibrinógeno: factor de riesgo o marcador de enfermedad vascular? / Fibrinogen: is it a risk factor or a marker of vascular disease?

El fibrinógeno (Fbg) es una glicoproteína plasmática, cuya molécula consiste en dos mitades idénticas, cada una de las cuales está compuesta por tres cadenas polipeptídicas diferentes. Mediante una serie de reacciones encadenadas el Fbg es convertido en fibrina insoluble. Es reactante de fase aguda e interviene en numerosas interacciones celulares: agregación plaquetaria, reología sanguínea, pinocitosis, crecimiento y migración celular, quimiotaxis e injuria de la célula endotelial. La síntesis del Fbg es pricipalmente hepática y está regulada por los "factores estimulantes del hepatocito" (Interleuquina-6, Factor Inhibitorio de Leucemia y Oncostatin M). Varios estudios epidemiológicos han demostrado una marcada asociación entre niveles elevados de Fbg y las enfermedades cardiovasculares isquémicas. El Fbg está relacionado con factores tales como el colesterol, glucemia, hipertensión, tabaquismo, alcohol, edad. Aún no se ha dilucidado si el incremento en los niveles de Fbg es factor de riesgo del evento oclusivo o si sólo es un marcador de la enfermedad vascular

Modificaciones del fibrinógeno en la trombosis en la altura / Fibrinogen changes in the high altitude thrombosis

Los estudios de rutina sobre la hemostasis no son los más indicados para anunciar en una fase precoz el establecimiento de una trombosis. Las anormalidades en el mecanismo de la coagulación de la fibrinolisis o de las plaquetas, están lejos de ser parámetros específicos directos que anuncie un riesgo de Trombosis en un paciente determinado. En los resultados de fibrinógeno y la Fibrinólisis, realizados en nuestro medio, se ha considerado a la hipoxia, como componente importante inductor de la Eritrocitosis en ciertas situaciones patológicas y que este factor agravaría el desarrollo de la trombosis en el nativo de la altura, pero estudios anteriores sobre este tema con relación a la función plaquetaria (Caen, J., Drovet, L. Ergueta J., Rodriguez A. 1972-1977) demostraron no ser evidentes. Realizamos un estudio protocolizado reciente, en 50 individuos nativos de la altura, cuyas edades fluctúan entre los 18 y 20 años de edad, en ellos se provocó una hipoxia local (venostasia) durante 10 minutos, con la finalidad de determinar los siguientes parámetros: Fibrinógeno, Fibrinólisis, Hematocrito y Grupos Sanguíneos, este último dato sirvió para relacionar la frecuencia de trombósis y valor de ésta proteína en los del grupo "O". La Fibrinólisis en ambos sexos nos demostró una aceleración en tiempo de 2 horas 15 minutos con relación a los de la costa que es >=3 horas. En el Hematocrito y la Hemoglobina encontramos que las mujeres del grupo sanguíneo "B" muestran una variación significativa en relación a los otros grupos sanguíneos. Los varones del grupo sanguíneo "A" y "O" mostraron también variaciones importantes.