Innate secretory immunity in response to laboratory stressors that evoke distinct patterns of cardiac autonomic activity

Mucosal surfaces are covered by the secretory proteins of the exocrine glands, which provide a first line of innate defense from infections. The release of these secretory proteins is, in theory, sensitive to modulation by psychosocial stress. This was tested by measuring salivary secretion in response to stressors known to evoke distinct patterns of cardiac autonomic activity. 32 subjects (Ss; mean age 23 yrs) were subjected to two laboratory stressors: an active coping memory test and a passive coping video presentation showing surgical procedures. The memory test produced a strong increase in sympathetic activity, and a decrease in cardiac parasympathetic activity. This active coping response was associated with an enhanced secretion of MUC7, lactoferrin, alpha-amylase, and total salivary protein. Conversely, the surgical video produced an increase in cardiac vagal tone and a modest increase in sympathetic activity. This passive coping response was associated with an enhanced secretion of all proteins studied. These secretory responses were generally larger than the secretory responses during the active coping memory test. For both stressors autonomic and cardiovascular reactivity was positively associated with an enhanced and prolonged secretory activity

Role of RhoA and rho kinase in lysophosphatidic acid-induced endothelial barrier dysfunction.

The online version of this article, along with updated information and services, is located on th

Path finding on a spherical self-organizing map using distance transformations

Spatialization methods create visualizations that allow users to analyze high-dimensional data in an intuitive manner and facilitates the extraction of meaningful information. Just as geographic maps are simpli ed representations of geographic spaces, these visualizations are esssentially maps of abstract data spaces that are created through dimensionality reduction. While we are familiar with geographic maps for path planning/ nding applications, research into using maps of high-dimensional spaces for such purposes has been largely ignored. However, literature has shown that it is possible to use these maps to track temporal and state changes within a high-dimensional space. A popular dimensionality reduction method that produces a mapping for these purposes is the Self-Organizing Map. By using its topology preserving capabilities with a colour-based visualization method known as the U-Matrix, state transitions can be visualized as trajectories on the resulting mapping. Through these trajectories, one can gather information on the transition path between two points in the original high-dimensional state space. This raises the interesting question of whether or not the Self-Organizing Map can be used to discover the transition path between two points in an n-dimensional space. In this thesis, we use a spherically structured Self-Organizing Map called the Geodesic Self-Organizing Map for dimensionality reduction and the creation of a topological mapping that approximates the n-dimensional space. We rst present an intuitive method for a user to navigate the surface of the Geodesic SOM. A new application of the distance transformation algorithm is then proposed to compute the path between two points on the surface of the SOM, which corresponds to two points in the data space. Discussions will then follow on how this application could be improved using some form of surface shape analysis. The new approach presented in this thesis would then be evaluated by analyzing the results of using the Geodesic SOM for manifold embedding and by carrying out data analyses using carbon dioxide emissions data

Effective treatment of edema and endothelial barrier dysfunction with imatinib

Background-Tissue edema and endothelial barrier dysfunction as observed in sepsis and acute lung injury carry high morbidity and mortality, but currently lack specific therapy. In a recent case report, we described fast resolution of pulmonary edema on treatment with the tyrosine kinase inhibitor imatinib through an unknown mechanism. Here, we explored the effect of imatinib on endothelial barrier dysfunction and edema formation. Methods and Results-We evaluated the effect of imatinib on endothelial barrier function in vitro and in vivo. In human macro- and microvascular endothelial monolayers, imatinib attenuated endothelial barrier dysfunction induced by thrombin and histamine. Small interfering RNA knock-downs of the imatinib-sensitive kinases revealed that imatinib attenuates endothelial barrier dysfunction via inhibition of Abl-related gene kinase (Arg/Abl2), a previously unknown mediator of endothelial barrier dysf Conclusions-Thus, imatinib prevents endothelial barrier dysfunction and edema formation via inhibition of Arg. These findings identify imatinib as a promising approach to permeability edema and indicate Arg as novel target for edema treatment. (Circulation. 2012;126:2728-2738.

Circulating angiopoietin-2 levels in the course of septic shock: relation with fluid balance, pulmonary dysfunction and mortality

Contains fulltext : 79899.pdf (publisher's version ) (Closed access)PURPOSE: To investigate whether angiopoietin-2, von Willebrand factor (VWF) and angiopoietin-1 relate to surrogate indicators of vascular permeability, pulmonary dysfunction and intensive care unit (ICU) mortality throughout the course of septic shock. METHODS: In 50 consecutive mechanically ventilated septic shock patients, plasma angiopoietin-2, VWF and angiopoietin-1 levels and fluid balance, partial pressure of oxygen/inspiratory oxygen fraction and the oxygenation index as indicators of vascular permeability and pulmonary dysfunction, respectively, were measured until day 28. RESULTS: Angiopoietin-2 positively related to the fluid balance and pulmonary dysfunction, was higher in non-survivors than in survivors and independently predicted non-survival throughout the course of septic shock. VWF inversely related to the fluid balance and pulmonary dysfunction throughout the course of septic shock, was comparable between survivors and non-survivors and predicted non-survival on day 0 only. Angiopoietin-1 positively related to pulmonary dysfunction throughout the course, but did not differ between survivors and non-survivors. CONCLUSIONS: In contrast to VWF, plasma angiopoietin-2 positively relates to fluid balance, pulmonary dysfunction and mortality throughout the course of septic shock, in line with a suggested mediator role of the protein