La soja en la prevención de la enfermedad cardiovascular / Soy in the prevention of cardiovascular disease

Los alimentos de soja o aislados de proteína de soja contienen dos componentes bioactivos principales, las isoflavonas (ISF) asociadas con la proteína de soja y los péptidos generados a partir de las dos principales proteínas de la soja, B-conglicina y la glicina. Algunos componentes de la dieta con soja controlan las funciones de adhesión del endotelio vascular, mediante la regulación de los mecanismos claves de control de las moléculas de adhesión endoteliales, la función de la integrina en los monocitos, citoquinas y quimoquinas en el control del tráfico y migración de los monocitos. También podrían regular la oxLDL en la generación y regulación de la expresión de los recogedores de radicales libres. La dieta con soja y otras dietas con efectos antiinflamatorios pueden bloquear el proceso inflamatorio asociado con la aterogénesis, reduciendo así el riesgo de ECV. Se requieren de más estudios que aclaren tanto a nivel experimental como clínico los mecanismos de acción de las ISF en la protección cardiovascular (AU)

Soy food or soybean protein isolates contain two major bioactive components, isoflavones (ISF) associated with soy protein, and peptides generated from two major soybean protein, B-conglycinin and glycine. Some components of the diet with soybean control the functions of vascular endotelial adhesion, by regulating the control key mechanisms of endothelial adhesion molecules, integrin function in monocytes, cytokines and chemokines in the traffic control and migration of monocytes. OxLDL may also regulate the generation and regulation of expression of catchers of free radicals. The diet with soy and other anti-inflammatory diets can block the inflammatory process associated with atherogenesis, thus reducing the risk of CVD. Further studies are required to clarify both experimental and clinical mechanism of action of the ISF cardiovascular protection (AU)

Análisis Multiplex de citoquinas intratecales en pacientes con deterioro cognitivo leve / Multiplex analysis of intrathecal cytokines in patients with mild cognitive impairment

Introducción. El estudio del papel de las citoquinas en los procesos neuroinmunológicos se ha intensificado en la última década, si bien los resultados han sido contradictorios debido al empleo de tecnologías poco sensibles. La implementación de la tecnología Multiplex en los inmunoensayos puede ser beneficiosa en la evaluación de pacientes con daño cognitivo leve (DCL) que evolucionan a enfermedad de Alzheimer (EA). Materiales y métodos. Treinta y siete pacientes con DCL y 24 sujetos control fueron estudiados mediante análisis Multiplex de citoquinas intratecales y en suero. Las variables del estudio fueron las citoquinas IL1β, IL2, IL5, IL6, IL7, IL8, IL10, IL12p70, IL13, factor necrosis tumoral alfa (TNFα), interferón gamma (IFNγ) y factor de crecimiento de granulocito-macrófago (GM-CSF) y los cocientes pro/antiinflamatorios IL6/IL10, IL6/IL5, IL8/IL10, IL8/IL5, TNFα/IL10 y TNFα/IL5. Se estudió la evolución a EA en los pacientes DCL y en los sujetos control en el período de un año. Resultados. Se encontraron diferencias significativas (p<0,05) para el cociente IL6/IL10 entre el grupo DCL y el grupo control (mediana [rango intercuartílico]): (1,39 [1,18-1,80] vs. 1,91 [2,68-1,18] pg/ml). De 37 pacientes con DCL, 14 evolucionaron a EA (DCL-EA) en el período de un año. De nuevo se encontraron diferencias significativas (p<0,05) en el cociente IL6/IL10 entre el grupo DCL-EA y DCL- S (o estable): (1,29 [0,84-1,56] vs. 1,42 [1,27-2,07] pg/ml). Ninguno de los sujetos control evolucionó a EA. Conclusiones. El descenso en el cociente IL6/IL10 en LCR puede ser un prometedor marcador diagnóstico de DCL y predictor/pronóstico de EA en DCL (AU)

Introduction. There has been an increase in the number of studies on the role of cytokines in neuro-immunological processes, over the last ten years, but some of these results have been contradictory due to a lack of sensitivity in the technology. The new Multiplex immunoassays can be beneficial for monitoring Mild Cognitive Impairment (MCI) patients who progress to Alzheimer Disease (AD). Methods. A study was conducted on 37 MCI patients and 24 control subjects by means of multiplex analysis of CSF cytokines. The variables measured were the following cytokines: IL1β, IL2, IL5, IL6, IL7, IL8, IL10, IL12p70, IL13, tumour necrosis factor alpha (TNFα), interferon gamma (IFNγ) and granulocyte – macrophage growth colony stimulating factor (GM-CSF), as well as the following pro/anti-inflammatory ratios: IL6/IL10, IL6/IL5, IL8/IL10, IL8/IL5, TNFα/IL10 and TNFα/IL5. Progress to AD in MCI patients was studied over a period of one year. Results. Significant differences were found (P<.05) for IL6/IL10 ratio between MCI patients and Control group (median [IR]): (1.39 [1.18-1.80] vs. 1.91 [2.68-1.18] pg/mL). Of the 37 MCI patients, 14 progressed to AD (DCL-EA group) within a year. Significant differences were also found (P<.05) for IL6/IL10 ratio between the DCL-EA group and the rest of MCI patients that did not progress (DCL-S or stable): (1.29 [0.84-1.56] vs. 1.42 [1.27-2.07] pg/mL). None of the control subjects progressed to AD. Conclusions. A decrease in CSF IL6/IL10 ratio could be a promising diagnostic biomarker in MCI and a prognostic biomarker of AD in MCI (AU)

Resistencia a insulina en el músculo esquelético: conexión con la obesidad / Obesity-Associated Insulin resistance in skeletal muscle

Entre las complicaciones asociadas a la Obesidad, tiene una especial relevancia el desarrollo de resistencia a la insulina, siendo el primer eslabón de una amplia patología conocida como diabetes tipo 2. La Obesidad se considera como un estado crónico de inflamación de baja intensidad, como indican los niveles circulantes elevados de moléculas proinflamatorias. Se ha propuesto al TNFα como el nexo de unión entre adiposidad y desarrollo de resistencia a insulina ya que la mayoría de los pacientes con diabetes tipo 2 son obesos y tienen aumentada la expresión de TNFα en sus adipocitos, y los animales obesos deleccionados para la función del TNFα o su receptor no desarrollan resistencia a insulina. Las citocinas proinflamatorias producidas por los adipocitos y/o macrófagos activan quinasas de estrés, proinflamatorias y factores de transcripción que actúan sobre los tejidos periféricos (entre ellos el músculo y el propio tejido adiposo) produciendo resistencia a la acción de la insulina, que es un defecto en la señalización a varios niveles. En concreto, el TNFα activa la quinasa p38MAPK que fosforila en residuos de serina a los IRSs, bloqueando su fosforilación en tirosina en respuesta a la insulina, tanto en adipocitos marrones como en miocitos. Muy recientemente hemos observado que la fosfatasa PTP1B también está implicada en la resistencia a insulina por TNFα en ambos modelos. En la clínica se está utilizando actualmente el tratamiento con tiazolidindionas en pacientes con diabetes tipo 2. Otros agonistas de receptores nucleares empiezan a aparecer en la bibliografía como potenciales sensibilizadores a acción de la insulina, entre ellos el LXR, que puede antagonizar la señalización proinflamatoria en los propios adipocitos y/o en el músculo (AU)

Insulin resistance is an important contributor to the pathogenesis of type 2 diabetes and obesity is a risk factor for its development, due in part to the fact that adipose tissue secretes proteins called adipokines that may influence insulin sensitivity. Among these molecules, TNFα has been proposed as a link between obesity and insulin resistance because TNFα is overexpressed in adipose tissues of obese animals and humans, and obese mice lacking either TNFα or its receptor show protection for developing insulin resistance. The direct exposure to TNFα induced a state of insulin resistance on glucose uptake in myocytes and brown adipocytes, due to the activation of pro-inflammatory pathways that impair insulin-signaling at the level of the IRS proteins. In this regard the residue Ser307 in IRS-1 has been identified as a site for TNFα- inhibitory effects in myotubes, with being p38MAPK and IKK involved in the phosphorylation of this residue. Conversely, serine phosphorylation of IRS-2 mediated by TNFα activation of MAPKs was the mechanism found in brown adipocytes. The phosphatase PTP1B acts as a physiological negative regulator of insulin signaling by dephosphorylating the phosphotyrosine residues of the insulin receptor and IRS-1, and PTP1B expression is increased in muscle and white adipose tissue of obese and diabetic humans and rodents. Moreover, up-regulation of PTP1B expression has recently been found in cells treated with TNFα. Accordingly, myocytes and primary brown adipocytes deficient on PTP1B are protected against insulin resistance by this cytokine. Furthermore, down-regulation of PTP1B activity is also possible by the use of pharmacological agonists of nuclear receptors that restored insulin sensitivity in the presence of TNFα. In conclusion, the lack of PTP1B in muscle and brown adipocytes increase insulin sensitivity and glucose uptake and could confer protection against insulin resistance induced by adipokines (AU)

El uso clínico de pruebas analíticas diagnósticas en las sepsis infantiles / Clinical use of diagnostic laboratory tests in childhood sepsis

No disponible

[Treatment of allergic rhinitis: update 2005]. / Therapie der allergischen Rhinitis. Mannschaftsaufstellung für die Allergiesaison 2005.

Potential approaches to the treatment of allergic rhinitis are the avoidance of allergens and medication with chromone compounds, antihistaminics and glucocorticosteroids. The sole causally effective treatment is specific immunotherapy. Leukotriene receptor antagonists, anti-IgE antibodies and monoclonal CD-4-molecules, as also soluble cytokine receptors are potential therapeutic options, the value of which currently remains unknown.

Hematopoietic secretory granules as vehicles for the local delivery of cytokines and soluble cytokine receptors at sites of inflammation.

Cytokines play an important role in the regulation of homeostasis and inflammation. A de-regulated cytokine function can subsequently promote chronic inflammation. This is supported by clinical evidence showing the beneficial effect of inhibiting TNF-alpha through injection of antibodies and soluble receptor in disorders such as rheumatoid arthritis and Crohn's disease. Systemic anti-TNF-alpha therapy however is associated with infectious complications. We therefore suggest a concept for the local deposition of therapeutically active agents into areas of inflammation or malignancy, based on the use of hematopoietic storage and secretory granules as delivery vehicles. Hematopoietic cells are induced to express the therapeutically active protein and to store it in the secretory lysosomes. The cells migrate into a tumour or site of inflammation, where the cells become activated and release the contents of their secretory lysosomes resulting in the local delivery of the therapeutically active protein. In support of this concept, gene transfer and granule loading can be achieved using the soluble TNF-alpha receptor (sTNFR1) after cDNA expression in hematopoietic cell lines. Endoplasmic reticulum (ER)-export can be facilitated by the addition of a transmembrane domain, and constitutive secretion can be prevented by incorporating a cytosol-sorting signal resulting in secretory lysosome targeting. The sTNFR1 is released from the transmembrane domain by proteolytic cleavage and finally, regulated sTNFR1-secretion can be triggered by a calcium signal. In vivo investigations are currently determining the feasibility of local protein delivery at sites of inflammation.