New interpretation of arterial stiffening due to cigarette smoking using a structurally motivated constitutive model

Cigarette smoking is the leading self-inflicted risk factor for cardiovascular diseases; it causes arterial stiffening with serious sequelea including atherosclerosis and abdominal aortic aneurysms. This work presents a new interpretation of arterial stiffening caused by smoking based on data published for rat pulmonary arteries. A structurally motivated “four fiber family” constitutive relation was used to fit the available biaxial data and associated best-fit values of material parameters were estimated using multivariate nonlinear regression. Results suggested that arterial stiffening caused by smoking was reflected by consistent increase in an elastin-associated parameter and moreover by marked increase in the collagen-associated parameters. That is, we suggest that arterial stiffening due to cigarette smoking appears to be isotropic, which may allow simpler phenomenological models to capture these effects using a single stiffening parameter similar to the approach in isotropic continuum damage mechanics. There is a pressing need, however, for more detailed histological information coupled with more complete biaxial mechanical data for a broader range of systemic arteries

A computational model of ureteral peristalsis and an investigation into ureteral reflux.

The aim of this study is to create a computational model of the human ureteral system that accurately replicates the peristaltic movement of the ureter for a variety of physiological and pathological functions. The objectives of this research are met using our in-house fluid-structural dynamics code (CgLes-Y code). A realistic peristaltic motion of the ureter is modelled using a novel piecewise linear force model. The urodynamic responses are investigated under two conditions of a healthy and a depressed contraction force. A ureteral pressure during the contraction shows a very good agreement with corresponding clinical data. The results also show a dependency of the wall shear stresses on the contraction velocity and it confirms the presence of a high shear stress at the proximal part of the ureter. Additionally, it is shown that an inefficient lumen contraction can increase the possibility of a continuous reflux during the propagation of peristalsis

Gradients in the in vivo intestinal stem cell compartment and their in vitro recapitulation in mimetic platforms

peer-reviewedIntestinal tissue, and specifically its mucosal layer, is a complex and gradient-rich environment. Gradients of soluble factor (BMP, Noggin, Notch, Hedgehog, and Wnt), insoluble extracellular matrix proteins (laminins, collagens, fibronectin, and their cognate receptors), stromal stiffness, oxygenation, and sheer stress induced by luminal fluid flow at the crypt-villus axis controls and supports healthy intestinal tissue homeostasis. However, due to current technological challenges, very few of these features have so far been included in in vitro intestinal tissue mimetic platforms. In this review, the tightly defined and dynamic microenvironment of the intestinal tissue is presented in detail. Additionally, the authors introduce the current state-of-the-art intestinal tissue mimetic platforms, as well as the design drawbacks and challenges they face while attempting to capture the complexity of the intestinal tissue’s physiology. Finally, the compositions of an “idealized” mimetic system is presented to guide future developmental efforts

Development of cell-based tests for the detection of new unwanted effects of anthropogenic substances in water

Die etablierten Testmethoden der aquatischen Ökotoxikologie basieren meist auf Vitalitätsuntersuchungen von Testorganismen oder liefern Nachweise von z. B. hormonaktiven Substanzen. Dies erlaubt jedoch nur eine begrenzte Aussage über andere unerwünschte Wirkungen der in der Probe vorhandenen Stoffe. In der Umwelt werden in den letzten Jahren vermehrt pharmazeutische Substanzen wie Entzündungshemmer gefunden. Ziel der durchgeführten Untersuchungen war daher, Testsysteme zu entwickeln, mit denen sowohl nicht akut-toxische als auch spezifische Effekte der Medikamente detektiert werden können. Als Basis der Testsysteme wurden murine Makrophagen sowie humane Lungenepithelzellen gewählt. Durch Zugabe von Endotoxinen oder Zytokinen lässt sich in diesen an der Immunantwort beteiligten Zellen der NF-κB Signalweg wie bei einer Entzündungsreaktion aktivieren. Zusätzlich wurden die Epithelzellen stabil mit einem NF-κB-Reporterplasmid transfiziert, so dass die Aktivierung von NF-κB direkt nachgewiesen werden konnte. Durch Zugabe von ausgewählten Pharmazeutika, definierten Mischungen oder Wasserproben konnten so die Effekte der Substanzen auf die NF-κB-Signalkaskade anhand der gebildeten Proteine untersucht werden. Außerdem sollten Genexpressionsanalysen einen umfassenden Überblick der Regulation von 84 NF-κB assoziierten Genen liefern. Mit Hilfe der Testsysteme konnten für zehn verschiedene Pharmazeutika keine Effekte auf die NF-κB-Aktivierung in umweltrelevanten Konzentrationsbereichen detektiert werden. Native Wasserproben aktivierten den Signalweg, was aber auf die Anwesenheit von Endotoxinen und/oder deren Bestandteile zurückgeführt werden konnte. Die Genexpressionsdaten zeigten kein Auffälligkeiten. Die grundsätzliche Funktionalität der Testsysteme konnte jedoch gezeigt werden, so dass eine Anwendung in der Umweltanalytik nach notwendigen Optimierungen möglich ist.The existing test methods in the field of aquatic eco-toxicology are mostly based on the analysis of vitality of test organisms or on the detection of hormonally active substances. However, these tests only allow a limited statement concerning unwanted effects of the sample. The most common compounds found in the environment are pharmaceutical substances such as anti-inflammatory drugs. The aim of these studies has therefore been to develop test systems with which both non-acute toxicity and specific effects of the drugs themselves can be detected. Murine macrophages and human lung epithelial cells were chosen as model test systems. The addition of endotoxins or cytokines activates the NF-κB signalling pathway in these cells which are involved in immune system reactions. Additionally, the epithelial cells were stably transfected with a reporter plasmid in order to show the activation of NF-κB directly. The addition of selected pharmaceuticals, defined mixtures or native water samples enabled an examination of the effects of the substances on the NF-κB signalling cascade via an analysis of the newly formed proteins. Furthermore, gene expression analysis gave an overview of the regulation of 84 NF-κB-associated genes. No effects on the activation of NF-κB could be observed for ten different pharmaceuticals in environmentally relevant concentrations. Native water samples activated the signalling pathway but this was attributable to the presence of endotoxins and/or their components. The gene expression data did not reveal any distinctive features. Thus, although the test systems are functional in principle, their application to environmental analyses will only be possible after further optimisation

Variation of Passive Biomechanical Properties of the Small Intestine along Its Length: Microstructure-Based Characterization

Multiaxial testing of the small intestinal wall is critical for understanding its biomechanical properties and defining material models, but limited data and material models are available. The aim of the present study was to develop a microstructure-based material model for the small intestine and test whether there was a significant variation in the passive biomechanical properties along the length of the organ. Rat tissue was cut into eight segments that underwent inflation/extension testing, and their nonlinearly hyper-elastic and anisotropic response was characterized by a fiber-reinforced model. Extensive parametric analysis showed a non-significant contribution to the model of the isotropic matrix and circumferential-fiber family, leading also to severe over-parameterization. Such issues were not apparent with the reduced neo-Hookean and (axial and diagonal)-fiber family model, that provided equally accurate fitting results. Absence from the model of either the axial or diagonal-fiber families led to ill representations of the force- and pressure-diameter data, respectively. The primary direction of anisotropy, designated by the estimated orientation angle of diagonal-fiber families, was about 35° to the axial direction, corroborating prior microscopic observations of submucosal collagen-fiber orientation. The estimated model parameters varied across and within the duodenum, jejunum, and ileum, corroborating histologically assessed segmental differences in layer thicknesses

Science probe

jil.1&2 , xv, 553 p. ; ill. : 30 cm