Creation of ventricular septal defects on the beating heart in a new pig model

Background/ Aims: So far, surgical and interventional therapies for muscular ventricular septal defects ( mVSDs) beyond the moderator band have had their limitations. Thus, alternative therapeutic strategies should be developed. We present a new animal model for the evaluation of such strategies. Methods: In a pig model ( n = 9), anterolateral thoracotomy was performed for exposure of the left ventricle. mVSDs were created under two- and three- dimensional echocardiography with a 7.5- mm sharp punch instrument, which was forwarded via a left ventricular puncture without extracorporeal circulation. Results: Creation of mVSDs was successful in all animals ( n = 9) confirmed by echocardiography, hemodynamic measurements and autopsy. The defects were located in the midmuscular ( n = 4), apical ( n = 1), inlet ( n = 2) and anterior part ( n = 2) of the muscular septum. All animals were hemodynamically stable for further procedures. The diameter and shunt volume of the mVSDs were 4.8 - 7.3 mm ( mean: 5.9 mm) and 12.9 - 41.3% ( mean: 22.1%), respectively. Autopsy confirmed in all animals the creation of a substantial defect. Conclusion: The described new technique for creation of an mVSD on the beating heart in a pig model is suitable for the evaluation of new therapeutic strategies for mVSD closure. Copyright (C) 2008 S. Karger AG, Basel

Creation of ventricular septal defects on the beating heart in a new pig model

Background/ Aims: So far, surgical and interventional therapies for muscular ventricular septal defects ( mVSDs) beyond the moderator band have had their limitations. Thus, alternative therapeutic strategies should be developed. We present a new animal model for the evaluation of such strategies. Methods: In a pig model ( n = 9), anterolateral thoracotomy was performed for exposure of the left ventricle. mVSDs were created under two- and three- dimensional echocardiography with a 7.5- mm sharp punch instrument, which was forwarded via a left ventricular puncture without extracorporeal circulation. Results: Creation of mVSDs was successful in all animals ( n = 9) confirmed by echocardiography, hemodynamic measurements and autopsy. The defects were located in the midmuscular ( n = 4), apical ( n = 1), inlet ( n = 2) and anterior part ( n = 2) of the muscular septum. All animals were hemodynamically stable for further procedures. The diameter and shunt volume of the mVSDs were 4.8 - 7.3 mm ( mean: 5.9 mm) and 12.9 - 41.3% ( mean: 22.1%), respectively. Autopsy confirmed in all animals the creation of a substantial defect. Conclusion: The described new technique for creation of an mVSD on the beating heart in a pig model is suitable for the evaluation of new therapeutic strategies for mVSD closure. Copyright (C) 2008 S. Karger AG, Basel

Assessment of the non-linear behaviour of plastic ankle foot orthoses by the finite element method

The stiffness characteristics of plastic ankle foot orthoses (AFOs) are studied through finite element modelling and stress analysis. Particular attention is given to the modelling and prediction of non-linear AFO behaviour, which has been frequently observed in previous experimental studies but not fully addressed analytically. Both large deformation effects and material non-linearity are included in the formulation and their individual influence on results assessed. The finite element program is subsequently applied to the simulation of a series of tests designed to investigate the relation between AFO trimline location and stiffness for moderate and large rotations. Through careful consideration and identification of key modelling parameters, the developed finite element solution proves to be a reliable and effective alternative means of assessing variations of a typical plastic AFO design so that particular patient requirements could be met, in the long ter

CD4(+) T Cells and Toll-Like Receptors Recognize Salmonella Antigens Expressed in Bacterial Surface Organelles

A better understanding of immunity to infection is revealed from the characteristics of microbial ligands recognized by host immune responses. Murine infection with the intracellular bacterium Salmonella generates CD4(+) T cells that specifically recognize Salmonella proteins expressed in bacterial surface organelles such as flagella and membrane vesicles. These natural Salmonella antigens are also ligands for Toll-like receptors (TLRs) or avidly associated with TLR ligands such as lipopolysaccharide (LPS). PhoP/PhoQ, a regulon controlling Salmonella virulence and remodeling of LPS to resist innate immunity, coordinately represses production of surface-exposed antigens recognized by CD4(+) T cells and TLRs. These data suggest that genetically coordinated surface modifications may provide a growth advantage for Salmonella in host tissues by limiting both innate and adaptive immune recognition

Evasion of Toll-like receptor 5 by flagellated bacteria

Toll-like receptor 5 (TLR5) recognizes an evolutionarily conserved site on bacterial flagellin that is required for flagellar filament assembly and motility. The α and ε Proteobacteria, including the important human pathogens Campylobacter jejuni, Helicobacter pylori, and Bartonella bacilliformis, require flagellar motility to efficiently infect mammalian hosts. In this study, we demonstrate that these bacteria make flagellin molecules that are not recognized by TLR5. We map the site responsible for TLR5 evasion to amino acids 89-96 of the N-terminal D1 domain, which is centrally positioned within the previously defined TLR5 recognition site. Salmonella flagellin is strongly recognized by TLR5, but mutating residues 89-96 to the corresponding H. pylori flaA sequence abolishes TLR5 recognition and also destroys bacterial motility. To preserve bacterial motility, α and ε Proteobacteria possess compensatory amino acid changes in other regions of the flagellin molecule, and we engineer a mutant form of Salmonella flagellin that evades TLR5 but retains motility. These results suggest that TLR5 evasion is critical for the survival of this subset of bacteria at mucosal sites in animals and raise the intriguing possibility that flagellin receptors provided the selective force to drive the evolution of these unique subclasses of bacterial flagellins