ABSTRACT
Low-molecular weight heparins (LMWH) are anticoagulants that have shown anti-inflammatory activity in several experimental models. Hot water burn inflammatory model accurately simulates human clinical situations allowing its use for nociception test and evaluation of anti-inflammatory drugs. The present study aims to evaluate the enoxaparin pretreatment on local and systemic inflammation biomarkers in the animal burn model. Inflammation was induced by submersing the rat left hind paw in water at 60o C for 60 s. C-reactive protein (CRP) and thrombin-antithrombin complex (TAT) were estimated by immunosorbent assay, fibrinogen (Fg) by the gravimetric method and paw oedema by orthogonal digital photography. Highest values of paw oedema, CRP and TAT were observed at 4 h post-burn while Fg peak occurs at 12 h post-burn; enoxaparin pretreatment decreased oedema (- 32.1%), and concentration of TAT (- 66.7%), PCR (- 37.9%) and Fg (- 8%). This study shows that enoxaparin has local and systemic anti-inflammatory effects and should be considered as a potential adjuvant drug for the treatment of burns.
Subject(s)
Biomarkers/metabolism , Burns/drug therapy , Enoxaparin/pharmacology , Inflammation/drug therapy , Animals , Anti-Inflammatory Agents/pharmacology , Anticoagulants/pharmacology , Antithrombin III/metabolism , Burns/metabolism , C-Reactive Protein/metabolism , Disease Models, Animal , Edema/drug therapy , Edema/metabolism , Heparin, Low-Molecular-Weight/pharmacology , Inflammation/metabolism , Male , Peptide Hydrolases/metabolism , Rats , Rats, Sprague-DawleyABSTRACT
Thrombin is essential for blood coagulation but functions also as a mediator of cellular signalling. Gene expression microarray experiments in human monocytes revealed thrombin-induced upregulation of a limited subset of genes, which are almost exclusively involved in inflammation and wound healing. Among these, the expression of F3 gene encoding for tissue factor (TF) was enhanced indicating that this physiological initiator of coagulation cascade may create a feed-forward loop to enhance blood coagulation. Activation of protease-activated receptor type 1 (PAR1) was shown to play a main role in promoting TF expression. Moreover, thrombin induced phosphorylation of ERK1/2, an event that is required for expression of thrombin-regulated genes. Thrombin also increased the expression of TF at the protein level in monocytes as evidenced by Western blot and immunostaining. Furthermore, FXa generation induced by thrombin-stimulated monocytes was abolished by a TF blocking antibody and therefore it is entirely attributable to the expression of tissue factor. This cellular activity of thrombin provides a new molecular link between coagulation, inflammation and wound healing.
Subject(s)
Gene Expression Regulation/drug effects , Inflammation/genetics , Monocytes/drug effects , Thrombin/pharmacology , Transcription, Genetic/drug effects , Wound Healing/genetics , Blood Coagulation/genetics , Cells, Cultured , Factor Xa/biosynthesis , Feedback, Physiological , Humans , MAP Kinase Signaling System/drug effects , MAP Kinase Signaling System/physiology , Monocytes/metabolism , Oligonucleotide Array Sequence Analysis , Real-Time Polymerase Chain Reaction , Receptor, PAR-1/physiology , Thromboplastin/biosynthesis , Thromboplastin/genetics , Up-Regulation/drug effectsABSTRACT
El presente trabajo tuvo como objetivo identificar el comportamiento de los factores de riesgo más importantes en las enfermedades del corazón y cerebrovascular en una comunidad atendida por médicos y enfermeras. Se tomó una muestra aleatoria sistemática por familia, como unidad muestral, con un intervalo de confianza de 95,9 % de los pacientes de seis consultorios del médico y la enfermera de la familia del área de salud del Policlínico “19 de Abril”, en Ciudad de La Habana , para un estudio analítico y de tipo caso-control, con el fin de conocer el comportamiento de los factores de riesgo más frecuentes en las enfermedades del corazón, cerebrovascular y en la hipertensión arterial. La población del estudio resultó en vejez demográfica con 27,33 % de los mayores de 60 años, y un predominio del sexo femenino con 56,82. La prevalencia de las enfermedades del corazón fue de 2,93 y de la cerebrovascular 0,53 %. Ambas se incrementaron con la edad, las primeras más frecuentes en el sexo femenino y las segundas en el masculino. En relación con el sexo, el hábito de fumar y el alcoholismo prevalecieron en el masculino y el resto en el femenino. Estos dos factores estuvieron asociados solamente con la enfermedad cardiovascular; el resto de ellos con las tres enfermedades. Fueron la hipercolesterolemia, la hipertensión arterial (HTA) , la diabetes 2, seguidas por la obesidad y el sedentarismo, en ese orden, los factores de riesgo de mayor fuerza de asociación y con más altos porcentajes del factor etiológico de riesgo. En los resultados de este trabajo se demuestra la fuerza de la asociación de los factores de riesgo seleccionados con las enfermedades estudiadas y se señala cuánto pudiera disminuir la carga de estas enfermedades, si se previenen o eliminan estos factores con la aplicación del enfoque de riesgo mediante las acciones de prevención primaria o primordial, secundaria y terciaria. Se requiere, además, que se realicen los esfuerzos para la promoción y la detección temprana de estos riesgos, muy especialmente en los jóvenes y en los menores de 15 años de edad.
The present paper was aimed at identifying the behaviour of the most important risk factors for heart & cerebrovascular diseases in a community cared for by physicians and nurses. As a sampling unit, a systematic random sample per family was taken (confidence interval 95,9%) from patients of six family physician´s offices located in the health area of "19 de Abril" polyclinics in the City of Havana. This sample was used in an analytical and case-control study to find out the behavior of the most frequent risk factors for heart, cerebrovascular and hypertensive diseases. The study population showed demographic aging with 27,33% of over 60 years-old persons, being females predominant with 56,82 % of the population Prevalence of heart diseases and of cerebrovascular diseases were 2,93 % and 0,53 % respectively. Both diseases increase their prevalence rates with age, the former were more frequent in females and the latter in males. As to sex analysis, smoking and alcoholism predominanted in males and the rest in females. These two factors were only associated to cardiovasular diseases but the rest of them related with the three types of diseases. Hypercholesterolemia, hypertension, diabetes 2, obesity and sedentary lifestyle, by this order, were the most associated risk factors with high percentages of etiological risk factor. The outcomes of this paper demonstrate the strong association of the selected risk factors with the studied diseases; they also indicated how much the burden of these diseases will lower if these factors are prevented or eliminated, by applying the risk approach through primary, secondary and tertiary pervention actions. It is also required that efforts are made in favor of promotion and early detection of these risks, particularly in young people and under 15 years-old teenagers.
ABSTRACT
Las exigencias sociales en un momento dado determinan los objetivos de la educación, y éstos se concretan en el contenido estrechamente vinculado con los métodos a utilizar en la enseñanza(AU)
