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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
11

Gap Junction Formation in Heart Valves in Response to Mechanical Loading

O'Malley, Karen L. 28 June 2013 (has links)
Valvular interstitial cells (VICs) are responsible for the maintenance of heart valve leaflet structure, however their responses to mechanical loading are not fully understood. Further characterization of VIC responses with regards to phenotype (quiescent or activated via ?-smooth muscle actin [?-SMA]) and communication (through gap junction proteins connexins 43 and 26) were studied. Tissue strips from porcine aortic, pulmonary, and mitral valves were cyclically stretched in the circumferential direction at normal and above normal membrane tensions for 48 hours at 1 Hz, 37°C, and 5% CO2. Unloaded tissues were statically incubated concurrently with loaded tissues, and fresh tissue controls were collected immediately. VIC phenotype was identified by ?- SMA via immunohistochemical staining and cell enumeration, as well as by gene expression via RT-PCR. Gap junction protein Cx43 was also evaluated via immunohistochemical staining and cell enumeration and by gene expression via RT-PCR, whereas Cx26 was evaluated using immunohistochemical staining and cell enumeration only. Within the range tested, it was found that mechanical loading did not affect ?-SMA or gap junction protein levels, nor were any differences in responses noted between valve types. However, the ?-SMA gene expression level was significantly lower in the mitral valve compared to the aortic and pulmonary valves. This may indicate a difference in the genetic response pathways among the valves, but not in the functional outcomes. This difference may be explained by embryological origins, since the mitral valve, unlike the aortic and pulmonary valves, contains only VICs and no neural crest cells.
12

Cost-Effective Synthesis, Bioactivity and Cellular Uptake Study of Aminoglycosides with Antimicrobial and Connexin Hemichannel Inhibitory Activity

Subedi, Yagya P. 01 December 2019 (has links)
Amphiphilic kanamycin is one of the promising class of compounds for the treatment of fungal infections in plants and animal. Factor that lead to the restricting of compounds for commercialization includes, the higher cost of production and poor stability of the compound. However, the new lead, identified from the synthesis and biological testing, can be synthesized on a large scale with a cost comparable to commercial antifungals. The newly reported lead is stable at the acidic and basic conditions. Additionally, this compound has an excellent activity towards Candida auris, a multidrug-resistant superbug. Heart disease is the leading cause of death in the United States most of which are caused by cardiac ischemia and arrhythmias. Abnormal opening of Cx43 hemichannel can damage the heart muscles and lead to these conditions. A compound which can selectively inhibit the opening of Cx43 hemichannel may pave the way to reducing the mortality rate of heart disease. A selective inhibitor towards Cx43 hemichannel is explored from the synthesis and biological testing of kanamycin derivatives. The synthesis of the new inhibitor is scalable and cost-effective.
13

Auswirkungen von Betablockern auf die Connexin43-Expression beim Sinusrhythmus und Vorhofflimmern

Rothe, Susanne Kerstin 05 March 2013 (has links)
Die Ergebnisse dieser Arbeit lassen vermuten, dass die Connexin43 Anordnung an der der Zellmembran humaner Herzmuskelzellen pharmakologisch beeinflussbar ist. Es ist bekannt, dass sich Connexin43 an der polaren und lateralen Zellmembran beim Vorhofflimmern und Sinusrhythmus unterschiedlich anordnet. Während beim Sinusrhythmuspatienten Connexin43 kaum an der lateralen Zellmembran zu finden ist, zeigt sich beim Vorhofflimmern vor allem an der lateralen Zellmembran eine verstärkte Connexin43 Anhäufung. Neben dem Rhythmustyp hat auch β-Adrenozeptorstimulation Einfluss auf die Connexin43 Expression. Aus diesem Grund untersucht die vorliegende Arbeit den Einfluss einer pharmakologischen Blockade der β-Adrenozeptoren durch Betablocker. Dafür wurden 38 die untersuchten Patienten anhand ihres Rhythmustyps, ihrer kardialen Begleiterkrankung und ihrer Pharmakotherapie (Betablocker: ja/nein) unterteilt und neben deren klinischen Daten ihre intraoperativ gewonnenen Herzohrbiopsien immunhistochemisch gefärbt und anschließend ausgewertet. Dabei zeigte sich, dass es zum einen zu einer unterschiedlichen Anordnung von Connexin43 bei den beiden Rhythmustypen kommt. Während beim Sinusrhythmus Connexin43 vor allem polar an der Zellmembran zu finden ist, ist es beim Vorhofflimmern vor allem an den lateralen Zellgrenzen zu finden. Betablockade geht hierbei vor allem beim Patienten mit Vorhofflimmern und Mitralklappenvitium mit einer Reduktion der Lateralisierung und einem positiven Effekt auf die Polarisierung einher.
14

Inverse relationship between tumor proliferation markers and connexin expression in a malignant cardiac tumor originating from mesenchymal stem cell engineered tissue in a rat in vivo model

Spath, Cathleen, Schlegel, Franziska, Leontyev, Sergey, Mohr, Friedrich-Wilhelm, Dhein, Stefan 29 July 2022 (has links)
Recently, we demonstrated the beneficial effects of engineered heart tissues for the treatment of dilated cardiomyopathy in rats. For further development of this technique we started to produce engineered tissue (ET) from mesenchymal stem cells. Interestingly, we observed a malignant tumor invading the heart with an inverse relationship between proliferation markers and connexin expression.
15

The Cx43 Carboxyl-Terminal Mimetic Peptide αCT1 Protects Endothelial Barrier Function in a ZO1 Binding-Competent Manner

Strauss, Randy E. 20 January 2022 (has links)
The Cx43 CT mimetic peptide, αCT1, originally designed to bind to ZO1 and thereby inhibit Cx43/ZO1 interaction, was used as a tool to probe the role of Cx43/ZO1 association in regulation of epithelial/endothelial barrier function. Using both in vitro and ex vivo methods of barrier function measurement, including Electric Cell-Substrate Impedance Sensing(ECIS), a TRITC-dextran transwell permeability assay, and a FITC-dextran cardiovascular leakage protocol involving Langendorff-perfused mouse hearts, αCT1 was found to protect the endothelium from thrombin-induced breakdown in cell-cell contacts. Barrier protection was accompanied by significant remodeling of the F-actin cytoskeleton, characterized by a redistribution of F-actin away from the cytoplasmic and nuclear regions of the cell, towards the endothelial cell periphery, in association with alterations in cellular orientation distribution. In line with observations of increased cortical F-actin, αCT1 upregulated cell-cell border localization of endothelial VE-cadherin, the Tight Junction protein Zonula Occludens 1 (ZO1) , and the Gap Junction Protein (GJ) Connexin43 (Cx43). A ZO1-binding-incompetent variant of αCT1, αCT1-I, indicated that these effects on barrier function and barrier-associated proteins, were likely associated with Cx43 CT sequences retaining ability to interact with ZO1. These results implicate the Cx43 CT and its interaction with ZO1, in the regulation of endothelial barrier function, while revealing the therapeutic potential of αCT1 in the treatment of vascular edema. / Doctor of Philosophy / Endothelial cells make up blood vessels within the heart and regulate the exchange of fluids between the circulation and heart tissue. In many forms of heart disease, the cardiac endothelium is disrupted, resulting in a damaging leakage and buildup of fluids within the heart. This work explores how a small peptide, derived from a naturally occurring molecule, may help to prevent fluid-associated damage to the heart by stabilizing the blood endothelium.
16

SELENIUM ET CARDIOPATHIES ISCHEMIQUES : effets d'une supplémentation nutritionnelle chez le rat

Rakotovao, Andry 03 November 2008 (has links) (PDF)
Dans le présent travail qui s'inscrit dans le cadre général de la protection du tissu cardiaque, nous avons mis en évidence les effets protecteurs d'un oligo-élément antioxydant, le sélénium, au cours du post-infarctus et tenté d'analyser les mécanismes cellulaires mis en jeu dans cet effet. <br />Dans une première partie, sur un modèle d'ischémie/reperfusion ex-vivo, nous démontrons qu'une alimentation enrichie en sélénium (1,5 mg/kg, po) limite significativement les arythmies ventriculaires malignes (AVM) dues à l'ischémie/reperfusion en améliorant le statut rédox cellulaire et en limitant la déphosphorylation de la connexine 43 (Cx43). Cette déphosphorylation, proportionnelle à l'intensité et à la sévérité du stress ischémique, entraîne des anomalies de l'excitabilité myocardique, responsables de l'apparition des AVM. Dans une deuxième partie, nous confirmons cet effet cardioprotecteur in-vivo. Dans ces conditions, le sélénium réduit significativement la mortalité due à l'ischémie myocardique et la taille de l'infarctus, et améliore le remodelage cardiaque précoce post-infarctus. Dans la troisième partie, nous montrons que ces effets protecteurs sont associés à une diminution significative du niveau cardiaque de TNF- et à une amélioration de la capacité antioxydante tissulaire à 8 jours post-infarctus. Enfin, nos résultats montrent que le statut en sélénium est inversement corrélé à la taille de l'infarctus et peut être modulé par l'ischémie/reperfusion. <br />Le statut préischémique en sélénium semble donc conditionner la sensibilité du myocarde à l'ischémie/reperfusion et déterminer le pronostic post-infarctus.
17

Exploring Gender Differences Throughout Normal Rat Aging - A Role for Estrogen Signaling in the Brain

Evola, Christopher Mark 07 May 2018 (has links)
No description available.
18

Funktionelle Rekonstitution von Connexonen in artifizielle Membranen: Expression, Reinigung und Charakterisierung von Connexin 43 / Functional reconstitution of connexons in artificial membranes: expression, purification and characterization of connexin 43

Carnarius, Christian 11 June 2012 (has links)
No description available.
19

3D-electron microscopic characterization of interstitial cells in the human bladder upper lamina propria

Neuhaus, Jochen, Schröppel, Birgit, Dass, Martin, Zimmermann, Hans, Wolburg, Hartwig, Fallier-Becker, Petra, Gevaert, Thomas, Burkhardt, Claus J., Minh Do, Hoang, Stolzenburg, Jens-Uwe 19 February 2018 (has links)
1) Aims To explore the ultrastructure of interstitial cells in the upper lamina propria of the human bladder, to describe the spatial relationships and to investigate cell-cell contacts. 2) Methods Focused ion beam scanning electron microscopy (FIB-SEM), 3-View SEM and confocal laser scanning microscopy were used to analyze the 3D ultrastructure of the upper lamina propria in male and female human bladders. 3) Results 3View-SEM image stacks as large as 59µm x 59µm x 17µm (xyz) at a resolution of 16nm x 16nm x 50 nm and high resolution (5nm x 5nm x 10nm) FIB-SEM stacks could be analyzed. Interstitial cells with myoid differentiation (mIC) and fibroblast like interstitial cells (fIC) were the major cell types in the upper lamina propria. The flat, sheet-like ICs were oriented strictly parallel to the urothelium sheet-like morphology. No spindle shaped cells were present. We furthermore identified one branched cell (bIC) with several processes contacting urothelial cells by penetrating the basal membrane. This cell did not make any contacts to other ICs within the upper lamina propria. We found no evidence for the occurrence of telocytes in the upper lamina propria. 4) Conclusions Comprehensive 3D-ultrastructural analysis of the human bladder confirmed distinct subtypes of interstitial cells. We provide evidence for a foremost unknown direct connection between a branched interstitial cell and urothelial cells of which the functional role has still to be elucidated. 3D-ultrastructure analyses at high resolution are needed to further define the subpopulations of lamina propria cells and cell-cell interactions.

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