Die vorgelegte Dissertationsschrift dient der Identifizierung des Mechanismus, über welchen neonatale Kardiomyozyten der Ratte biaxialen zyklischen Stretch wahrnehmen. Angriffspunkt dafür bildeten sowohl Stretch Activated Ion Channels (SAIC) als auch die mit Integrinen assoziierte Focal Adhesion Kinase (FAK). Die Inhibition der SAIC erfolgte mit Gadolinium und eine Blockade der FAK konnte durch den FAK-Inhibitor II erreicht werden. Eigens angelegte Zellkulturen wurden unter definierten Parametern für 24 Stunden unter Einwirkung genannter Stoffe gestretcht und anschließend einer Analyse mittels Immunfluoreszenz und Western Blot unterzogen. Gestretchte Kardiomyozyten richteten sich schräg zur Achse der einwirkenden Kraft aus und wiesen eine Polarisierung von Connexin 43 auf, außerdem zeigte sich dessen gesteigerte Expression. Durch die Blockade der FAK konnte lediglich eine aufgehobene Polarisierung von Connexin 43 bei unveränderter Expression und Ausrichtung der Kardiomyozyten festgestellt werden. Auch die Mikrotubuli veränderten nach Stretch ihre Orientierung bezogen auf die Zellachse. Die zunächst annähernde Parallelität der Fasern zeigte sich nach Inhibition der FAK deutlich aufgelockert. Für die Aktinfilamente konnte dies nicht nachgewiesen werden. Die Integrine dienen demnach der Wahrnehmung von Stretch und vermitteln die Polarisierung von Connexin 43 sowie die Orientierung der Mikrotubuli über die FAK. Für die anderen genannten Prozesse ist die Aktivierung eines FAK-unabhängigen Integrin-Signalweges denkbar. Gadolinium hatte insgesamt keinen Effekt auf beschriebene Veränderungen, sodass ein Einfluss der SAIC auf Stretch-induzierte Veränderungen in Kardiomyozyten ausgeschlossen werden konnte. Gleichzeitig konnte durch die Beobachtung der Polarisierung von Microtubule Organizing Center, Kinesin und Golgi-Apparat die Hypothese der sich durch Stretch orientierenden neonatalen Kardiomyozyte unterstützt werden, welche die Voraussetzung für die Anordnung von Connexin 43 an den Zellpolen darstellen könnte. Sowohl die Selbstorganisation des Myokards im Rahmen der Embryogenese als auch die Pathophysiologie verschiedener kardialer Erkrankungen könnte dadurch womöglich besser verstanden werden.

L’arbre bronchique constitue une large interface avec le milieu extérieur ce qui en fait notamment une sentinelle immunologique. Par ailleurs, il est soumis à de multiples contraintes physiques (variation de pressions lors du cycle ventilatoire) avec le développement de pathologies lorsque la réponse à ces contraintes est inadaptée. Au cours de ce travail, nous avons essayé de caractériser la réponse bronchique des voies aériennes distales à partir d’un modèle isolé de bronche humaine soumis à l’application d’un stretch unique ou cyclique tel qu’il est généré lors de la ventilation mécanique. D’un point de vue fonctionnel, le stretch unique ou cyclique s’accompagne d’une modification significative du tonus basal de la bronche avec deux étapes : l’une précoce apparaît au cours de l’exposition même des variations de tension pariétale, l’autre est tardive et apparaît à l’arrêt de l’étirement. Concernant l’étape précoce, elle se révèle robuste car aucun pré-traitement et particulièrement l’abrasion de l’épithélium ne la supprime totalement. La caractérisation de cette réponse implique notamment la voie des NO synthases et des Rho-A kinase. La réponse tardive fait quant à elle intervenir l’épithélium ainsi que la voie des NO-synthase suggérant un rôle prépondérant du NO. Par contre, ces modifications de force au repos sont indépendantes de la sécrétion de médiateurs inflammatoires détectés par ELISA. L’approche génétique renforce par contre le rôle du tissu de soutien bronchique en activant la synthèse de collagène (MMP-9). Au total l'application d'une contrainte cyclique renforce la bronchoconstriction par inhibition de la voie des NOsynthases et de la mécanotransduction. / The tracheo-bronchial tree is a true immunologic sentinel related to the huge interface with the external environment. Moreover, it is submitted to variable physical strains (tidal ventilation and variation in pressure) and an excessive response leads to the genesis of some pathology as hyperresponsiveness. The aim of this work on an isolated organ model was to characterize the human bronchial response to a single or repetitive and physiological stretch as observed during mechanical ventilation. From a functional perspective, a single strain or a cyclic stretch significantly increased the basal tone of the human bronchus with a two-step response: the early response appears during cycling and the delayed after the stretch has ceased. The early response is robust then no pre-treatment and especially epithelial removal totally inhibits it. This response implies NO synthase and Rho-A kinase pathway with a reduction of the developed basal tone with these inhibitors. As it concerns the late response, it involved epithelium and NO synthase suggesting a prominent action of NO. Inflammatory mediators are not directly involved in the rise of basal tone because stretch-induced secretion as detected with ELISA is very low. Genomic approach transiently activates transcription of genes for MMP-9, involved in the collagen production and consequently in the support tissue of the bronchial tree. As a conclusion, cyclic stretch enhances bronchoconstriction by inhibition of the NO-synthase pathway and mechanotransduction.

Thesis (Ph. D.)--Oregon State University, 2006. / Blank pages 143 and 159 not microfilmed. Includes bibliographical references. Also available online (PDF file) by a subscription to the set or by purchasing the individual file.

Thesis (Ph. D.)--Oregon State University, 2006. / Blank pages 143 and 159 not microfilmed. Includes bibliographical references.

Bakgrund: Fotleden används dagligen och en nedsatt fotledsrörlighet kan orsaka många problem för personer i vardagen. Knäböj är en rörelse som används både i vardagen samt i träningssammanhang och kräver en god dorsalflexion i fotleden. Det är därför värdefullt att som fysioterapeut veta vilken metod som ökar dorsalflexion inför ett rehabiliteringsprogram där knäböj ingår. Syfte: Sammanställa litteraturen gällande akuta effekter av dynamisk och statisk stretching samt posterior talocrural glide på dorsalflexion i talocruralleden hos friska individer, definierat som personer utan fysiologisk sjukdom eller trauma med eventuell påverkan på fotleden. Studien syftar även till att värdera graden av evidens för behandlingarna. Metod: Litteratursökning utfördes i databasen PubMed. Slutligen inkluderades åtta studier med sammanlagt 141 deltagare. Samtliga studier kvalitetsgranskades enligt PEDro scale, därefter användes SBU:s GRADE för evidensbedömning. Resultat: Statistisk signifikant ökning på dorsalflexion för samtliga metoder med liknande utslag på rörlighet, med liten fördel för statisk stretch. Kvalitetsgranskning enligt PEDro scale visar på att fem studier anses vara av måttlig till hög kvalitet och tre anses vara av låg kvalitet. Otillräckligt vetenskapligt underlag för posterior talocrural glide, statisk och dynamisk stretch på dorsalflexion. Konklusion: Statisk stretch, dynamisk stretch och posterior talocrural glide ökar dorsalflexionen efter minst två minuters behandling. Evidensen talar för att samtliga metoder ger liknande utfall på dorsalflexionen med en liten fördel för statisk stretch, men fler studier behövs för att bekräfta resultatet. / Background: Demands are put on the ankle daily. Limited ankle range of motion can present problems during daily activities. The squat is a movement performed both in everyday life as well as in the context of training and requires ample dorsiflexion of the ankle. Therefore, it is of value to physiotherapists to know which method should be used to increase dorsiflexion in a rehabilitation protocol where the squat is included. Objective: To provide an overview of the acute effects of static and dynamic stretching as well as posterior talocrural glide in healthy individuals without physiological diseases or trauma relating to the ankle. The study will also assess the level of evidence surrounding each of these methods. Method: The database PubMed was used to search for the included studies. A total of eight studies was included in this review, with a total of 141 participants. Study quality was judged using PEDro scale, after which SBU’s GRADE was used to determine the level of evidence for each method. Result: A statistically significant increases present for each of the methods, with similar outcomes on the dorsiflexion. Assessing the quality of the included studies with PEDro scale resulted in five studies of moderate to high quality and three of low quality. Evidence supporting posterior talocrural glide, static and dynamic stretching is deemed insufficient according to SBU’s GRADE. Conclusion: Dorsiflexion is increased after two minutes of static and dynamic stretching as well as posterior talocrural glide. The evidence suggests that similar increases are present with each method, with static stretch showing a slightly higher result. However further research is required to confirm the result.

L’hypertension pulmonaire (HTP) est la principale pathologie de la circulation pulmonaire. Elle secaractérise par une augmentation maintenue de la pression dans les artères intrapulmonaires (AIP) (> à 25mmHg au repos). Cette pression exerce des forces d’étirement au niveau des cellules musculaires lisses desartères intrapulmonaires (CML d’AIP). Au niveau des CML, des canaux mécanosensibles appelés des SAC(« stretch-activated channels ») permettent de transformer un stimulus mécanique d’étirement en uneréponse biologique de contraction : c’est le tonus myogénique. Le Ca2+ est un second messager cellulairequi peut être aussi bien mobilisé depuis le milieu extracellulaire que depuis les réserves calciquesintracellulaires. Une augmentation de sa concentration cytoplasmique induit la contraction des CML. Grâceà des techniques de patch-clamp, de microspectrofluorimétrie, d’immunomarquages et à une approchepharmacologique, nous avons mis en évidence les voies de signalisations calciques qui sont mises en placeà la suite d’un étirement des CML d’AIP. Les expériences ont été réalisées à la fois chez des rats normaux etsur deux modèles de rats présentant une HTP (rats hypoxique chroniques et rats monocrotalines). Lesrésultats montrent que chez les rats normaux un étirement induit un influx de Ca2+ par les SAC. Cet influxcalcique est amplifié par (1) une hyperpolarisation de la membrane plasmique via l’activation de canauxBKCa, (2) une sortie de Ca2+ par les récepteurs à la ryanodine de type 1 (RyR1) du réticulum sarcoplasmique(RS) sous-membranaire. Afin de rétablir l’homéostasie calcique, les mitochondries tamponnent le Ca2+cytosolique. Chez les rats souffrant d’HTP, l’influx de Ca2+ par les SAC et l’amplification calcique par les RyRsont plus importants. Cette amplification est due à une réorganisation des réserves calciquesintracellulaires, notamment chez les rats monocrotalines. De plus, une association fonctionnelle entre lesréserves calciques du RS et les cavéoles conduit à des réponses calciques plus importantes après unétirement chez les rats HTP. Enfin, nous avons mis en évidence la présence de canaux mécanosensiblesPiezo1 dans les AIP de rats. En conclusion, l’organisation spatiale des partenaires calciques au sein des CMLd’AIP est importante pour la signalisation cellulaire et joue un rôle majeur dans l’HTP. / Pulmonary hypertension (PH) is the main disease of the pulmonary circulation. This pathology ischaracterized by an increase of the intrapulmonary arterial (PA) pressure at rest (> 25 mmHg). This pressureexerts stretch forces on pulmonary arterial smooth muscle cells (PASMC). Stretch-activated channels (SAC)are present in PASMC and are able to transform a mechanical stimulus of stretch into a biological responseof contraction, a phenomenon called myogenic tone. Ca2+ is a second messenger that can be mobilizedfrom both the extracellular medium and intracellular Ca2+ stores. An increase of the intracellular Ca2+concentration ([Ca2+]i) leads to PASMC contraction. Using patch-clamp, microspectrofluorimetry,immunostainings and a pharmacological approach, we highlight Ca2+ signaling pathways induced by stretchin PASMC. Experiments were performed in normal rats and in two models of PH (chronically hypoxic ratsand monocrotaline rats). We showed that in normal rats a stretch induces a Ca2+ influx through SAC whichis amplified by (1) a plasma membrane hyperpolarization by BKCa channels and (2) a Ca2+ amplification bysubplasmalemnal ryanodine receptor 1 (RyR) of the sarcoplasmic reticulum (SR). Besides, mitochondria areinvolved in buffering cytoplasmic Ca2+. In PH rats, the Ca2+ influx by SAC and the Ca2+ release by RyR areenhanced due to a reorganization of intracellular Ca2+ stores. Furthermore, a functional associationbetween SR and caveolae conduce to a much greater amplification of the stretch-induced Ca2+ increase inPH rats. Finally, we showed that the mechanosensitive channel Piezo1 is expressed in PA. To conclude, thespatial organization of Ca2+ stores in PASMC is important for cell signaling and plays a casual role in PH.

A correlation between the USU stretch test and the pizza fork test would allow the stretch properties of Mozzarella cheese to be measured objectively. The Utah State University (USU) Stretch Test uses a modified texture-profile analyzer to pull strands of cheese from a melted reservoir, measuring the load exerted on the probe during stretching. Parameters measured by the USU stretch test include Melt Strength (FM), which is the maximum load exerted on the probe, Stretch Load (SL), which is the load exerted on the probe at any specified point following FM, and Stretch Extension (SE), which was defined as the extension of the probe at a selected load. To begin with, it was determined that the greatest repeatability and cheese performance was obtained by tempering 50 g of shredded cheese for 45 min at 65°C and using a three-pronged hook with a diameter of 25 mm as the probe. These conditions were then applied in a correlation study in which a low correlation was seen between the USU stretch test and the pizza fork test, with the greatest correlation being seen with FM (R2 = 0.22). A more extensive look at the effect of the tempering temperature used in the USU stretch test on the degree of correlation between the two tests was conducted by tempering cheeses at 65, 70, 75, 80, and 85 °C. In this experiment, the highest correlation between the two tests was seen at both 80 and 85°C. Values of R2 at 80°C for SL10-15 and SEF (Stretch Extension at FM) were 0.75 and 0.70, respectively. At 85°C, the highest degree of correlation was seen at SL10-15 (R2 = 0.72) and SE0.1 (R2 = 0.69). A multiple linear correlation study was also conducted. A high degree of correlation between the USU stretch test and the pizza fork test was seen at 80°C when two parameters were used (SEF and SL22, R2 = 0.85, Adj. R2 = 0.80) and when four parameters were used (FM, slope from 10 to 20 em, SE0.1, and SL22, R2 = 0.97, Adj. R2 = 0.93). A set of cheese was then analyzed by the USU stretch test and the pizza fork test at three different intervals of aging (21 , 40, and 60 days after manufacture). This data was combined with previously collected data to show that the USU stretch test can be used to characterize the functional properties of a cheese using the parameters of FM, SEF, as well as SE0.1. It was concluded that the USU stretch test can provide a better characterization of a pizza cheese than can the pizza fork test. Whereas the pizza fork test is only able to record the distance that the cheese can stretch, the USU stretch test is capable of measuring a variety of parameters, which provides not only an indication of how far the cheese will stretch, but also other important functional properties related to the cheese, such as viscosity, elasticity, and the thickness of the strands being stretched.

No description available.

No description available.

The purpose of this research was to correlate the applied material properties of stretch film with its elastic properties measured in a laboratory setting. There are currently no tools available for a packaging engineer to make a scientific decision on how one stretch film performs against another without applying the film. The system for stretch wrap comparison is mostly based on trial and error which can lead to a significant loss of product when testing a new film or shipping a new product for the first time. If the properties of applied stretch film could be predicted using a tensile test method, many different films could be compared at once without actually applying the film, saving time and money and reducing risk. The current method for evaluating the tensile properties of stretch film advises the user apply a hysteresis test to a standard sample size and calculate several standard engineering values. This test does not represent how the material is actually used. Therefore, a new tensile testing method was developed that considers the film gauge (thickness) and its prestretch. The results of this testing method allowed for the calculation of the material stiffness (Bisha Stiffness) and were used to predict its performance in unit load containment. Applied stretch film is currently compared measuring containment force, which current standards define as the amount of force required to pull out a 15.2cm diameter plate, 10.1cm out, located 25.4cm down from the top and 45.7cm over from the side of a standard 121.9cm width unit load. Given this definition, increasing the amount of force required to pull the plate out can be achieved by manipulating two different stretch film properties, either increasing the stiffness of the film or increasing the tension of the film across the face of the unit load during the application process. Therefore, for this research, the traditional definition of containment force has been broken down into two components. Applied film stiffness was defined as the amount of force required to pull the film a given distance off the unit load. Containment force was defined as the amount of force that an applied film exerts on the corner of the unit load. The applied stretch film was evaluated using two different methods. The first method used the standard 10.1cm pull plate (same plate as ASTM D 4649) to measure the force required to pull the film out at different increments from the center on the face of the unit load. This measurement force was transformed into a material stiffness and film tension (which were subsequently resolved into containment force). The second, newly developed, method involved wrapping a bar under the film, on the corner of the unit load, and pulling out on the bar with a tensile testing machine. This method allowed for the direct measurement of the containment force and material stiffness. The results indicated that while some statistically significant differences were found for certain films, the material stiffness and containment were relatively consistent and comparable using either method.The use of the Bisha Stiffness to predict the applied stiffness and containment force yielded a statistically significant correlation but with a very low coefficient of determination. These results suggest that while film thickness and prestretch are key variables that can predict applied stiffness and containment force, more research should be conducted to study other variables that may allow for a better. High variability of the predictions observed were caused by the differences in film morphology between the different method of elongation (tensile vs application). This study was the first that attempted to define and correlate the tensile properties of stretch film and the applied properties of stretch film. From this research many, terms have been clarified, myths have been dispelled, formulas have been properly derived and applied to the data collected and a clear path forward had been laid out for future researchers to be able to predict applied stiffness and containment force from the elastic properties of stretch film. / Ph. D.