Development of a Computational Model of Abscess Formation.

In some bacterial infections, the immune system cannot eliminate the invading pathogen. In these cases, the invading pathogen is successful in establishing a favorable environment to survive and persist in the host organism. For example, S. aureus bacteria survive in organ tissues employing a set of mechanisms that work in a coordinated and highly regulated way allowing: (1) efficient impairment of the immune response; and (2) protection from the immune cells and molecules. S. aureus secretes several proteins including coagulases and toxins that drive abscess formation and persistence. Unless staphylococcal abscesses are surgically drained and treated with antibiotics, disseminated infection and septicemia produce a lethal outcome. Within this context, this paper develops a simple mathematical model of abscess formation incorporating characteristics that we judge important for an abscess to be formed. Our aim is to build a mathematical model that reproduces some characteristics and behaviors that are observed in the process of abscess formation.

Novel sulfated xylogalactoarabinans from green seaweed Cladophora falklandica: Chemical structure and action on the fibrin network.

The water-soluble sulfated xylogalactoarabinans from green seaweed Cladophora falklandica are constituted by a backbone of 4-linked ß-l-arabinopyranose units partially sulfated mainly on C3 and also on C2. Besides, partial glycosylation mostly on C2 with single stubs of ß-d-xylopyranose, or single stubs of ß-d-galactofuranose or short chains comprising (1→5)- and/or (1→6)-linkages, was also found. These compounds showed anticoagulant activity, although much lower than that of heparin. The effect of a purified fraction (F1) on the fibrin network was studied in detail. It modifies the kinetics of fibrin formation, suggesting an impaired polymerization process. Scanning electron microscopy showed a laxer conformation, with larger interstitial pores than the control. Accordingly, this network was lysed more easily. These fibrin properties would reduce the time of permanence of the clot in the blood vessel, inducing a lesser thrombogenic state. One of the possible mechanisms of its anticoagulant effect is direct thrombin inhibition.

Glicosaminoglicanos en hemostasia: Acción del dermatán sulfato sobre el sistema fibrinolítico / Glycosaminoglycans on hemostasis: Dermatan sulfate action on the fibrinolytic system

El dermatán sulfato (DS) es un glicosaminoglicano endógeno, ampliamente conocido por su acción anticoagulante mediante su interacción con el cofactor II de la heparina para potenciar la inhibición de trombina. En los últimos años se ha sugerido que además el DS aumentaría la actividad fibrinolítica, aunque el mecanismo aún no ha sido completamente dilucidado. En este trabajo se presenta una revisión detallada de los resultados propios y una discusión de la bibliografía disponible respecto de la evaluación del efecto del DS sobre el sistema fibrinolítico. En estudios de activación fibrinolítica, por métodos amidolíticos y coagulométricos, el DS mostró tener efecto pro-fibrinolítico mediante potenciación de la activación de plasminógeno por t-PA y uPA, efecto independiente de su conocida acción anticoagulante. En estudios de caracterización de fibrina, las redes obtenidas en presencia de DS presentaron fibras más largas y delgadas que las redes control, mayor grado de compactación y de lisabilidad; efecto pro-fibrinolítico asociado a su acción anticoagulante. Los resultados presentados contribuyen al esclarecimiento del mecanismo de acción del DS sobre el sistema plasminógeno-plasmina y permiten plantear hipótesis sobre el rol fisiológico de este glicosaminoglicano.

Dermatan sulfate (DS) is well-known for its anticoagulant activity by binding to heparin cofactor II in order to enhance the antithrombin action. It has also been suggested that DS has a profibrinolytic effect, although the exact molecular mechanism is unknown. This review exposes the results obtained and discusses on the available literature on DS effect on the fibrynolytic system. DS exhibited a stimulating effect on the activation of plasminogen by plasminogen activators (t-PA and u-PA), by in vitro amidolytic and coagulometric methods, showing a pro-fibrinolytic effect independent of its known anticoagulant action. Studies of fibrin networks obtained in the presence of DS showed longer and thinner fibers than controls, increased degree of compaction and lisability. Thus, DS displayed a pro-fibrinolytic effect associated to its anticoagulant action. These results contribute to clarify the mechanism of DS action on the plasminogen-plasmin system and to the understanding of the physiologic role of this glycosaminoglycan.