Rozprawy doktorskie na temat „Alveolar mechanics”
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Liu, Hui. "The application of alveolar microscope on alveolar mechanics of ventilator-induced lung injury". [S.l. : s.n.], 2008. http://nbn-resolving.de/urn:nbn:de:bsz:25-opus-61847.
Pełny tekst źródłaDash, Shari Anne Ahmed El. "Estudo tomográfico de pressões de colapso alveolar e níveis isogravitacionais em pulmões de pacientes com SDRA e LPA". Universidade de São Paulo, 2009. http://www.teses.usp.br/teses/disponiveis/5/5159/tde-25062009-113611/.
Pełny tekst źródłaA prospective clinical study performed on 11 patients with ARDS or ALI with the intention of studying the regional behavior of lung tissue density and alveolar collapse along the three spatial axes. An initial recruitment maneuver was followed by multiple semi-complete CT scans at descending levels of PEEP. Multiple linear regression (R2=0.83) showed a gravitational gradient of densities and collapse (p<0.001) and no cephalo-caudal (p<0.001) or right-toleft increase (p<0.05), corroborating the liquid-like behavior of the lung. Pressure exerted by mediastinal structures, chest wall and effusions is transmitted uniformly throughout the lung. PEEP has a homogenizing effect on lung parenchyma. Among commonly used clinical surrogates, Pflex showed the worst correlation with actual lung collapse, while arterial PO2 and compliance were equivalent.
Namati, Eman, i eman@namati com. "Pre-Clinical Multi-Modal Imaging for Assessment of Pulmonary Structure, Function and Pathology". Flinders University. Computer Science, Engineering and Mathematics, 2008. http://catalogue.flinders.edu.au./local/adt/public/adt-SFU20081013.044657.
Pełny tekst źródłaRolle, Trenicka. "Lung Alveolar and Tissue Analysis Under Mechanical Ventilation". VCU Scholars Compass, 2014. http://scholarscompass.vcu.edu/etd/3398.
Pełny tekst źródłaLiao, Pinhu. "Mechanotransduction in alveolar epithelial cells subjected to mechanical strain". Thesis, Imperial College London, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.479153.
Pełny tekst źródłaChen, Shanze [Verfasser], i Silke [Akademischer Betreuer] Meiners. "Molecular mechanism of alveolar macrophage polarization and cell communication with alveolar epithelial cell / Shanze Chen. Betreuer: Silke Meiners". München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2015. http://d-nb.info/1080479074/34.
Pełny tekst źródłaMcKechnie, Stuart R. "The roles of hyperoxia and mechanical deformation in alveolar epithelial injury and repair". Thesis, University of Edinburgh, 2008. http://hdl.handle.net/1842/2691.
Pełny tekst źródłaFois, Georgio [Verfasser]. "Response of alveolar type II pneumocytes to mechanical stimulation / Giorgio Fois". Ulm : Universität Ulm. Medizinische Fakultät, 2012. http://d-nb.info/1019167831/34.
Pełny tekst źródłaDickie, A. John. "Mechanisms by which endotoxin-stimulated alveolar macrophages impair lung epithelial sodium transport". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape11/PQDD_0025/MQ51593.pdf.
Pełny tekst źródłaMossadeq, Sayeed. "Kinetics and mechanisms of accumulation for liposomal ciprofloxacin into rat alveolar macrophages". VCU Scholars Compass, 2013. http://scholarscompass.vcu.edu/etd/501.
Pełny tekst źródłaRummel, Sebastian. "Mechanisms of alveolar protein clearance in isolated rabbit lungs : role of clathrin and caveolae mediated endocytosis of albumin by the alveolar epithelium /". Giessen : VVB Laufersweiler, 2007. http://d-nb.info/988285827/04.
Pełny tekst źródłaFreire, Filho Francisco Wagner Vasconcelos. "Estudo comparativo dimensional e da resistencia mecanica de dois sitemas nacionais de distratores osteogenicos alveolares justa-osseos". [s.n.], 2003. http://repositorio.unicamp.br/jspui/handle/REPOSIP/289441.
Pełny tekst źródłaTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba
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Resumo: O objetivo deste trabalho foi comparar dois sistemas de distratores osteogênicos alveolares justa-ósseos de 9mm de abertura máxima de fabricação nacional. Foram analisadas duas marcas comerciais (Grupo I e Grupo II), através das avaliações dimensionais dos distratores e parafusos, da resistência à tração dos distratores e da resistência à flexão e à torção dos parafusos. Na avaliação dimensional foram utilizados dez distratores de cada fabricante e quarenta parafusos, sendo dez de cada tamanho oferecido, 1,3 x 5mm e 1,3 x 7mm do grupo I e 1,5 x 5mm e 1,5 x 7mm do grupo II. Os dados foram submetidos ao teste dos postos assinalados de Wilcoxon para os distratores e o teste de Friedman para os parafusos. No teste de resistência à tração foram utilizados dez distratores de cada marca comercial e os resultados submetidos ao teste t Student. No teste de resistência à flexão foram utilizados quarenta parafusos e aplicados os testes F e de Tukey, ao nível de significância de 5%. No teste de resistência à torção, foram utilizados dez parafusos de cada fabricante, sendo do tipo 1,3 x 5mm do grupo I e 1,5 x 5mm do grupo II e os resultados submetidos ao teste t Student. Os distratores do grupo II apresentaram menor variação das mensurações realizadas, porém não houve diferença estatística entre os parafusos de ambas as marcas. Os distratores do grupo II foram estatisticamente mais resistentes à tração. Os parafusos de 1,5x5mm do grupo II foram os mais resistentes à flexão e à torção
Abstract: The aim of this study was to perform a comparative analysis between two different alveolar distractions devices, of 9mm length, built by manufactured in Brazil. These two different devices were provided by companies (group I and group II). The analysis consisted of a macroscopic assessment from the distraction devices and its screws, followed by a traction resistance of the devices and torsion and bending resistance of the screws. Were used, for macroscopic assessment, ten distraction devices and forty screws, which included ten screws of every length offered by each company. Data was submitted to the Wilcoxon test for devices and Friedman test for screws. Ten distraction devices from each company were used for the traction resistance, and its results were submitted to the Student t test. Forty screws were used for the bending resistance. Values were compared trough F and Tukey test, with 5% significance. For the torsion resistance, ten screws from each company were used. The 1.3 X 5mm screws from group I and the 1.5 X 5mm from group II were chose to realize this test, and its results were submitted to the Student t test. Devices from group II presented less variation of its measurements, but there were not any statistical difference between the screws. Group II devices were tatistically more resistant to traction. Screws 1.5x5mm, produced by group II, were more resistant to bending and to torsion
Doutorado
Cirurgia e Traumatologia Buco-Maxilo-Faciais
Doutor em Clínica Odontológica
Rummel, Sebastian [Verfasser]. "Mechanisms of alveolar protein clearance in isolated rabbit lungs : role of clathrin- and caveolae-mediated endocytosis of albumin by the alveolar epithelium / eingereicht von Sebastian Rummel". Giessen : VVB Laufersweiler, 2008. http://d-nb.info/988773570/34.
Pełny tekst źródłaGavara, i. Casas Núria. "Contractile response of alveolar epithelial cells to biochemical or mechanical stimulation probed by traction microscopy". Doctoral thesis, Universitat de Barcelona, 2007. http://hdl.handle.net/10803/1146.
Pełny tekst źródłaGENERAL AIM
The general aim of this thesis was to study the generation of contractile force by human alveolar epithelial cells in culture in response to biochemical or mechanical stimuli using traction microscopy.
SPECIFIC AIMS
1. To implement a traction microscopy setup to measure the contractile force generated by human alveolar epithelial cells in culture.
1.1. To implement and validate a software to determine the deformation field induced by adhered cells on the elastic substrate, following previously described algorithms.
1.2. To implement and validate a software to determine the traction field induced by adhered cells and other contractility parameters, following previously described algorithms.
1.3. To implement a software to determine the contour of an adhered cell from a brightfield or phase contrast image of the cell.
2. To study the contractile response of human alveolar epithelial cells in response to thrombin.
2.1. To determine the gel substrate conditions and gel fabrication procedure which enable suitable cell culture and optimal detection of traction forces exerted by human alveolar epithelial cells. These gel conditions include: concentration of polyacrilamide gel components to provide optimal gels stiffness; concentration of fluorescent beads to optimally compute gel deformation; and suitable gel coating to enable cell attachment.
2.2. To determine the gel elastic properties (Young's modulus) by atomic force microscopy.
2.3. To measure the time-course of the contractile response to thrombin challenge.
2.4. To study the distribution of contractile forces exerted by adhered cells before and after thrombin stimulation.
2.5. To measure actin polymerization and reorganization induced by thrombin challenge.
2.6. To study the role of the actin cytoskeleton in the contractile response to thrombin by pre-treatments with cytochalasin D.
2.7. To study the role of pathways signalling MLC phosphorilation in the contractile response to thrombin by pre-treatments with ML7 and Y-27632.
3. To study the contractile response of human alveolar epithelial cells subjected to stretch.
3.1. To determine a suitable gel substrate that firmly attaches to a flexible membrane, allowing biaxial stretch application (max ~15%) and cell culture.
3.2. To determine the gel elastic properties (Young's modulus) of the gel at different strain levels by atomic force microscopy.
3.3. To implement and validate a stretching device to apply controlled biaxial and uniform strains to cultured cells and simultaneously measure contractile forces by deforming the gel substrate to which they are adhered.
3.4. To adapt the existing traction microscopy algorithms and software to allow computation of large bead displacements (~20 μm) and corresponding stretch fields.
3.5. To measure contractile forces exerted by human alveolar epithelial cells before, during and after being subjected to a stepwise deformation of up to 11.5% linear strain.
3.6. To assess the role of actin polymerization in the contractile response to stretch.
3.7. To assess the role of actomyosin crossbridges attachment or detachment in the contractile response to stretch.
3.8. To assess temporal changes in cell contractility after stretch release.
"Estudi de la contracció de cèl·lules epitelials alveolars en resposta a estímuls inflamatoris i de deformació mitjançant microscopia de tracció"
TEXT:
L'epiteli alveolar forma una barrera cel·lular semipermeable entre l'espai alveolar i l'interstici del pulmó, permetent l'intercanvi gasós a la vegada que restringeix el pas de líquid, macromolècules i cèl·lules cap a l'alvèol. El trencament de la monocapa, degut a la formació de forats entre cèl·lules adjacents, pot donar lloc a l'augment de la permeabilitat i l'entrada de líquid a l'alvèol, característics del dany pulmonar agut. La integritat de la monocapa epitelial es regeix per un equilibri dinàmic de forces als punts d'unió cèl·lula-cèl·lula, i cèl·lula-matriu. Les forces en joc es divideixen en una component de tensió centrípeta i una component d'adhesió centrífuga. La component centrípeta es deguda a les forces de contracció generades activament per la maquinària contràctil cel·lular i el retrocés passiu degut a la deformació cíclica a la que es troben sotmeses les cèl·lules alveolars durant la respiració. Per tal de garantir la integritat de la monocapa, les forces d'adhesió han de ser capaces de contrarestar la tensió centrípeta. L'equilibri de forces als punts d'unió pot veure's compromès degut a estímuls inflamatoris o bé mecànics.
El projecte de tesi es centra en el paper de les forces actives de contracció sobre la integritat de la monocapa alveolar en resposta a estímuls característics del dany pulmonar agut. Per tal d'estudiar aquesta component contràctil, el present projecte ha utilitzat la microscopia de tracció. Aquesta tècnica permet mesurar la força que cèl·lules adherents aïllades realitzen sobre el seu substrat, així com la seva distribució espaial i evolución temporal. La tècnica consisteix en cultivar cèl·lules adherents sobre substrats elàstics que contenen microesferes fluorescents. Comparant la posició de les microesferes quan la cèl·lula es troba adherida al substrat i un cop aquesta ha estat desenganxada amb tripsina, podem calcular la força que la cèl·lulaadherent realitzava sobre el substrat.
El projecte de tesi inclou dos estudis concrets, dedicats a dos estímuls característics de dany pulmonar agut als qual poden trobar-se sotmeses les cèl·lules epitelials alveolars. El primer estudi (secció 3) es centra en l'efecte que el mediador inflamatori trombina provoca sobre la realització de forces contràctils per part de cèl·lules alveolars epitelials. El segon estudi (secció 4) es centra en la resposta contràctil de cèl·lules alveolars epitelials a l'aplicar deformacions externes, simulant les condicions de respiració mecànica que requereixen molts pacients amb dany pulmonar agut.
Armstrong, Lynne. "Tumour necrosis factor-alpha regulation in human alveolar macrophages : mechanisms in health and acute lung injury". Thesis, University of Bath, 1995. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.307115.
Pełny tekst źródłaHiguita-Castro, Natalia. "Micro/Nano Scale Modeling of Cellular injury and Inflammation in the Alveolar Microenvironment during Mechanical Ventilation". The Ohio State University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=osu1385516912.
Pełny tekst źródłaUsmani, Shariq M. [Verfasser]. "Calcium signaling mechanisms in alveolar epithelial cells : Effects of physiological and patho-physiological perturbations / Shariq M. Usmani". Konstanz : Bibliothek der Universität Konstanz, 2011. http://d-nb.info/1019938889/34.
Pełny tekst źródłaKramer, Barbara [Verfasser]. "Collagen vascular diseases associated with interstitial lung diseases : analysis of alveolar epithelial cellular stress mechanisms / Barbara Kramer". Gießen : Universitätsbibliothek, 2017. http://d-nb.info/1127506692/34.
Pełny tekst źródłaAmbrósio, Aline Magalhães. "Estudo da influência das manobras de recrutamento alveolar sobre a mecânica, a ventilação e o parênquima pulmonar durante lesão aguda promovida pela instilação de ácido clorídrico: estudo experimental em porcos". Universidade de São Paulo, 2005. http://www.teses.usp.br/teses/disponiveis/10/10137/tde-29092006-201943/.
Pełny tekst źródłaDifferent mechanical ventilation strategies which define limits of intrathoracic pressures and volumes are being proposed for patients with acute respiratory distress syndrome (ARDS). These recommendations are based on observations that mechanical ventilation with excessive tidal volumes or insufficient values of positive end expiratory pressure (PEEP) can cause severe lung injury due to overinflation. The aim of the present study was to apply recruitment maneuvers (RM) and PEEP in lungs submitted to acute lung injury (ALI) due to the administration of hydrochloride acid. Twenty four female Landrace Largewhite pigs, weighing 25 to 35 Kg were used. After anesthesia, animals were submitted to volume controlled mechanical ventilation (6 to 8ml/kg) and were randomly allocated in four groups of 6 animals each: GI animals without ALI and treated with progressive values of PEEP (5, 10, 15 and 20 cmH2O) or regressive (20 to 5 cm H2O); GII animals without ALI and treated with progressive values of PEEP (5, 10, 15 and 20 cmH2O) or regressive (20 to 5 cm H2O) plus 3 consecutive recruitment maneuvers with 30 cmH2O; GIII animals submitted to 1 hour of ALI and treated as GI; GIV animals submitted to 1 hour of ALI and treated as GII. Parameters of respiratory mechanics, ventilation and oxygenation were measured each 20 minutes according to the change of the PEEP values. ALI could be observed by the severe changes of oxygenation and respiratory mechanics noted. The use of RM and PEEP were able to restore control values. Nevertheless, application of high values of PEEP and CPAP were accompanied by significant hemodynamic changes which could be evidenced in animals without ALI. Derecruitment probably occurred when PEEP value reached 5 cmH2O. The lung lesions were uniform in the HCL-injured animals and consisted of necrosis, hemorrhage, congestion, and inflammatory cells infiltration that involved both the interstitium and the alveoli. The experimental model of lung injury was adequate to the study of RM followed by PEEP since significant changes of the oxygenation and compliance values could be observed 1 hour after acid instillation. PEEP values of 5cmH2O were incapable to maintain recruitment at the end of the observation period, while 10 cmH2O were sufficient to promote the reestablishment of oxygenation index with minimal hemodynamic changes. Compliance did not improve during the maneuvers. Further studies are necessary to confirm the results obtained, especially to show that the maintenance of a PEEP value of 10 cmH2O are sufficient to maintain recruitment after the RM
Wang, Huiyan. "Toxicity and signaling mechanisms underlying interactions of Stachybotrys chartarum toxins with lung macrophages". University of Cincinnati / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1319487821.
Pełny tekst źródłaFaron, Matthew Leon. "Examining mechanisms of virulence gene regulation and the early host interactions in Francisella tularenisis". Diss., University of Iowa, 2014. https://ir.uiowa.edu/etd/1595.
Pełny tekst źródłaNahle, Sara. "Réponse macrophagique aux nanomatériaux carbonés : effets de leur caractéristiques physiques et chimiques sur le transcriptome Carbon-based nanomaterials induce inflammation and autophagy in rat alveolar macrophages Single wall and multiwall carbon nanotubes induce different toxicological responses in rat alveolar macrophages Gene expression profiling of alveolar macrophages exposed to non-functionalized, anionic or cationic multi-walled carbon nanotubes shows three different mechanisms of toxicity Cytotoxicity and global transcriptional responses induced by zinc oxide nanoparticles NM 110 in PMA-differentiated THP-1 cells Protein and lipid homeostasis altered in rat macrophages after exposure to metallic oxide nanoparticles". Thesis, Université de Lorraine, 2019. http://www.theses.fr/2019LORR0142.
Pełny tekst źródłaCarbon nanomaterials (CNM) are widely used in the industrial world and they have many applications. The absence of legislation controlling their preparation and uses makes necessary, as for all nano-objects, the study of their toxicity in order to determine the risk of human exposure and to adapt legislation accordingly. Therefore, a better knowledge of their toxic potential is necessary. The increasing difficulties in using animal models make necessary the development of studies using cell lines especially macrophages that play a predominant role. These CNM are very light and form easily aerosols, reason why the preferred models for toxicity studies are alveolar macrophages. However, there are no human alveolar macrophage lines currently but rat cells exist. The subject of my thesis is to study macrophages response to CNM and the understanding of the effect of their physical and chemical characteristics on the transcriptome. The CNM studied are multiwall carbon nanotubes (CNT), single wall CNT, carbon black and graphene oxide. Our results show that all CNM studied trigger an inflammatory reaction in NR8383 and differentiated THP-1 cells, also some of them induce cytotoxicity. Size, functionalization and form control CNM toxicity mechanisms: CNT with similar size alter identical signaling pathways, amino group functionalization produces lysosomal stress, whereas functionalization with carboxyl groups causes reticulum endoplasmic (RE) stress, nanotubes induce cytoskeleton disorganization more than spherical nanoparticles. Otherwise, we identified lipid accumulation in NR8383 cells due to RE stress induced by Mitsui-7, a multiwall CNT. There was also a fusion of these macrophages. The formation of these foam cells and giant multi-nucleus cells are key events leading to granulomas formation. The results obtained are an important support for understanding CNM effects, showing some significant toxicity at molecular level. This toxicity is dependent on the physical and chemical characteristics of these nanomaterials. Thus, based on this type of data, we can move towards a safer manufacture to avoid the risks associated with their exposure
Lanças, Tatiana. "Responsividade do tecido pulmonar periférico de pacientes com doença pulmonar obstrutiva crônica". Universidade de São Paulo, 2009. http://www.teses.usp.br/teses/disponiveis/5/5144/tde-08032010-155914/.
Pełny tekst źródłaUp to 60% of COPD patients can present airway hyperresponsiveness. However, it is not known whether the peripheral lung tissue also presents an exaggerated response to agonists in COPD. In this study we investigated the in vitro mechanical behavior and structural and inflammatory changes of peripheral lung tissue of 10 COPD patients and compared to 10 non-smoking controls. We measured resistance (R) and elastance (E) of lung strips at baseline and after acetylcholine (ACh) challenge. We further assessed the alveolar tissue density of neutrophils, eosinophils, macrophages, mast cells and CD8+ and CD4+ cells, and the content of -smooth muscle actin+ cells, elastic fibers and collagen fibers. Values of R after ACh treatment (RACh) and percent increase of tissue resistance (%R) were significantly higher in COPD group compared to controls (p0.03). There was a significantly higher density of macrophages (p=0.04) and CD8+ cells (p=0.017) and a lower elastic fiber content (p=0.003) in COPD group compared to controls. We observed a significant positive correlation between %R and eosinophil and CD8+ cells density (r=0.608, p=0.002; and r=0.581, p=0.001, respectively), and also a negative correlation between %R and FEV1/FVC (r=-0.451, p<0.05). We conclude that the cholinergic responsiveness of parenchymal lung strips is increased in COPD patients and seems to be related to alveolar tissue eosinophilic and CD8 lymphocytic inflammation and also to the degree of airway obstruction at pulmonary function test.
Avena-Barthelemy, Anne. "Comportement a long terme de materiaux composites immerges a grande profondeur". Paris, ENMP, 1987. http://www.theses.fr/1987ENMP0049.
Pełny tekst źródłaLiu, Hui [Verfasser]. "The application of alveolar microscope on alveolar mechanics of ventilator-induced lung injury / vorgelegt von Hui Liu". 2009. http://d-nb.info/992111439/34.
Pełny tekst źródłaTsang, Melanie Elizabeth. "Molecular mechanisms of LPS detection by human alveolar epithelial cells". 2005. http://link.library.utoronto.ca/eir/EIRdetail.cfm?Resources__ID=362440&T=F.
Pełny tekst źródłaKuo, Tsung-Chen, i 郭俊成. "Studies on the Toxicological Mechanisms of Methylmercury in Rat Alveolar Macrophages". Thesis, 1997. http://ndltd.ncl.edu.tw/handle/16312312456143551201.
Pełny tekst źródła國立臺灣大學
毒理學研究所
85
Mercury compounds of both natural and industrial origin are wide- spread environmental pollutants. Organic mercury compounds have been involved in large-scale poisoning episodes. Human exposure to mercurials occurs in the production of batteries, in chloralkali plants, gold mining, dentistry, and the use of grain fungicides. Although the primary targets of mercury compounds have been identified as the nervous systems and the kidney, toxic effects on other organ systems have also been reported. Of particular concern are the effects of mercury compounds on the immune system, which include effects of methylmercury (MeHg) on T cells, B cells, and natural killer cells. Although mercury compounds are considered to be immunosuppressive agents, their effects on the alveolar macrophages are still not clear. The important function of alveolar macrophages has been recognized to be a mediator of a variety of essential biologic activities, particularly in the acute inflammatory response and tissue repair. Therefore we attempted to study the effect of MeHg on rat alveolar macrophages. The Mechanism of MeHg-induced Apoptosis of Alveolar Macrophages First of all, through the use of a scanning electron microscope, we have found that alveolar macrophages treated with 10 mM of MeHg for 24 hrs showed a decrease of surface microvilli, and those treated with 15 m M of MeHg underwent deformity and subsequent cell death. To investigate their death patterns, we aspirated DNA from alveolar macrophages and analyzed them by gelelectrophoresis. We discovered that the DNA ladder phenomenon became more obvious as the MeHg increased in concentration. When we intracellularly applied 5 mM EGTA to eliminate calcium ions, we observed a decrease of the ladder phen omenon. Zinc at 1 mM had a similar inhibitory effect. Moreover, an apoptosis peak was observed on flow cytometry analysis of DNA stained with propidium iodide. Alveolar macrophages stained with Hoechst 33342 demonstrated apoptotic bodies induced by MeHg. From the above data, we know that MeHg can induce a typical apoptosis in alveolar macrophages. As we moved on to study the mechanism of apoptosis as induced by MeHg in alveolar macrophages, we discovered that MeHg could increase the intracellular calcium ion concentration and decrease the pH in alveolar macrophages. To find out which endonuclease was responsible for the MeHg-induced DNA fragmentation of alveolar macrophages, we aspirated the nuclear proteins of alveolar macrophages and test them under different pH values and in conditions with or without calcium ions, and discovered that the endonuclease activity was calcium-dependent without relations to pH values. Therefore, MeHg first increased the calcium level, which in turn increased the endonuclease activity and induced DNA fragmentation and apoptosis. Study on MeHg-induced Necrosis and Apoptosis of PMNs Mediated by Calcium and Acid Mercury is not only an environmental pollutant, but a drug with clinical use as well. The neutrophils is a kind of phagocytic cell that plays the role of a scavenger in human bodies, so it has a greater chance of exposure to MeHg. By evaluating the cytotoxicity of MeHg on PMNs, we can better understand the actions of MeHg. Addition of MeHg of 10 mM to the PMNs increased the intracellular calcium ion concentration and induced a drop in pH, which reached a trough at the 100th second before gradually returning to a neutral value. When the extracellular calcium was eliminated by 5 mM EGTA, the first phase disappeared, but the second phase remained. The L-type calcium channel blocker verapamil was able to block the first phase. These results testified that the first phase of calcium ion increase induced by MeHg was mediated by a clacium channel, while the second phase resulted from the calcium ion release from the intracellular calcium ion storage pool. When we used propidium iodide (PI) to investigate the MeHg-induced neutrophils death, we discovered that the cytotoxicity of 15 mM MeHg augmented as the extracellular calcium ion concentration increased. On the contrary, when we lowered the extracellular calcium ion level with 5 mM EGTA, the toxicity of MeHg lessened significantly. Therefore, the MeHg toxicity is closely associated with the amount of influx of extracellular calcium ions. Moreover, we found out that neutrophils treated with 10 mM MeHg for 24 hrs manifested chromatin condensation, apoptotic bodies and the formation of DNA ladder. Therefore, neutrophils apoptosis was closely related to the decrease of intracellular pH caused by MeHg in a concentration-dependent fashion. Another finding that supports this view is that MeHg, EGTA and zinc can all cause DNA ladders, and they can also induce intracellular acidification. Among them, MeHg decreased the intracellular pH in a concentration-dependent manner. When we analyzed the influence of pH and calcium on the endonuclease activity by its ability to cut plasmid DNA, we found out that the endonuclease was not activated either with or without calcium at neutral pH, but the activation took place in acidic solutions at pH below 6.5 whether or not there was any calcium present. Therefore, MeHg activates an acid-sensitive endonuclease within neutrophils, which in turn induces neutrophils apoptosis. The Influence of MeHg on the Immune Functions of Alveolar Macrophages and the Mechanism of Cellular Signal Transduction The influence of MeHg on the immune functions of alveolar macrophages were approached in three aspects. When not stimulated, alveolar macrophages produces minimal NO and TNF-a, which make analysis very difficult. For this reason, we studied the influence of MeHg on the LPS-induced NO and TNF-a production, and found out that MeHg had a significant inhibitory effect on both of them. As we investigated the possible mechanism, we discovered that LPS increased NO and TNF-a by increasing the activity of receptor tyrosine kinase, which could be inhibited by genistein. H7 and staurosporine could also inhibit the production of LPS-NO, but H7 and H89 was unable to inhibit the production of LPS-TNF-a, which could be inhibited by W7 (20mM). An interesting finding was that the inhibition of c-AMP (1 mM) was far greater than the production of LPS-TNF-a. In our study of the inhibitory effect of MeHg on LPS-NO and LPS-TNF-a by intercepting the signal transduction, we found out that H89 (PKA inhibitor) could antagonize the inhibition of MeHg on LPS-NO, but genistein, H7 and staurosporine failed to manifest this inhibitory effect. The inhibitory effect of MeHg on LPS-TNF-a could be antagonized by H89 in a concentration- dependent manner. H7 also had the antagonistic effect, while genistein and staurosporine failed to show any influence at all. As we moved further to study the mechanism by which H89 antagonized the inhibitory effect of MeHg on LPS-NO and LPS-TNF-a, we found out it was related to MeHg-induced increase of intracellualr calcium, which in turn activated Ca-dependent adenylate cyclase, which then increased the activity of c- AMP-PKA. PKA induced the phosphorylation and subsequent inactivation of raf-1, leading to the MeHg-induced inactivation of ERK. Finally we were able to prove that MeHg indeed produced its inhibitory effect via this signal transduction pathway, making NOS protein significantly lower than the LPS control group. In our study of the mechanism by which MeHg inhibited the phagocytic activity of alveolar macrophages (FITC-latex bend uptake), we found out that genistein, H-7 and staurosporine had no influence at all, but W-7 at 50 mM significantly enhanced the inhibitory effect of MeHg. It was therefore inferred that MeHg might via the Ca2+-activated calmodulin kinase pathway. MeHg-induced Functional Low-conductance Calcium-dependent Potassium Currents As we use the patch-clamp techniques to study the membrane current, we discovered that MeHg could open a potassium channel. MeHg generated by a pressure-injector induced an outward current Io(MeHg) at -40 mV. The removal of extracellular calcium or verapamil reduced its amplitude, and intracellular dialysis with 5 mM EGTA completely inhibited this outward current. Intracellular dialysis with heparin (5 mg/ml) also significantly reduced the amplitude. Therefore, this outward current was calcium-dependent. It was completely blocked by potassium channel inhibitors quinine (0.2 mM) and 4-aminopyridine (1 mM). The MeHg action was also completely blocked by small-conductance potassium channel inhibitors such as apamin (1 mM) and dequalinium (0.5 mM). When we replace the potassium ions with cesium ions, this current was totally inhibited as well. These findings suggest that MeHg opens a Ca2+-dependent K+ channel. As we analyzed the single channel current, we found out that the conductance of this potassium channel was 12.0 pS and 8.1 pS when the pipette solution was 145 mM and 36 mM respectively. There has been no report so far as to the possible influence of this small-conductance K+ channel on the functions of alveolar macrophages. In our study, after we blocked the potassium channels of alveolar macrophages with potassium channel inhibitor dequalinium, we discovered that it had no significant influence on LPS-induced release of TNF-a and NO after 24 hrs of incubation, but it manifested a significant antagonistic effect on the MeHg inhibition of TNF-a and NO production. Another potassium channel blocker quinine had a similar antagonistic action. On the other hand, pretreatment with 1 mM dequalinium significantly inhibited MeHg-induced increase in intracellular calcium ion concentration. Therefore, by inhibiting the activation of this potassium channel, it was possible to alter the TNF-a inhibition caused by MeHg-induced intracellular calcium increase. In our study of the relationship between membrane currents and the mechanism by which MeHg caused cell death, we discovered that MeHg probably caused cellular apoptosis by increasing calcium ion level, and that the potassium channel activated by the increase of calcium ion was able to lower the toxicity of MeHg. The Influence of MeHg on the Proton Current When we tried to detect intracellular pH changes with BCECF, we discovered that MeHg induced a drop in intracellular pH and activated a proton channel. MeHg generated by a pressure-injector induced an outward current at +20 mV which was completely blocked by intracellular dialysis with 5 mM EGTA. Moreover, calcium ions given directly through the pipette also induced a calcium- dependent outward current, which increased in amplitude as the concentration of calcium ions increased. This current was not changed by a replacement of intra- and extracellular ions with Cs, Asp or NMDG-Asp. Both ion substitation experiments and their reversal potential distinctly dependent on the pHi suggest, this current is mainly caused by protons. As we observed the intracellular pH changes, we found that a bath application with 20 mM MeHg caused an immediate acidification of the cell, closely followed by its alkalization. In our attempt to detect the production of O2-, low-concentration of MeHg induced the production of O2-, while MeHg at a high concentration manifested an inhibitory effect. This proton current could be inhibited by such channel blockers as Cd2+ (1 mM), Zn2+ (1 mM) and DQ (10 mM). Calmodulin antagonist (W-7) and calmodulin kinase inhibitor KN- 93 can almost completely inhibit this H+ conductance. Therefore, we first discovered that the rat alveolar macrophages have a Ca2+- calmodulin-dependent proton conductance, which can be regulated by calmodulin-kinase. Zn2+, a blocker of this proton conductance, enhances the MeHg inhibition of the phagocytic activity and of the NO production, but has a reversing effect on the MeHg inhibition of TNF-a release. In conclusion, after we studied the mechanism of the toxicity of MeHg on rat alveolar macrophages, we found out that MeHg acted on the membrane channels and caused an influx of extracellular calcium. Moreover, it was able to induce a calcium release from the intracellular storage pool and therefore increased the intracellular calcium level. On one hand, this increase of calcium level activated calcium-dependent endonuclease leading to apoptosis. On the other hand, it induced calcium-dependent adenylate cyclase-Raf-1 phosphorylation, thus inhibiting the production of NO and TNF- a. In addition, the increase of intracellular calcium level activated Ca2+- calmodulin-kinase, which in turn induced the phosphorylation of membrane H+-channel protein and generated the H+-current. This explained why MeHg quickly lowered the intracellular pH but immediately returned it to a neutral value. The increase of intracellular calcium triggered the alteration of multifunctional signalling pathways of the cell. The opening of protective calcium- dependent potassium channels was also initiated by the MeHg- induced calcium increase.
Chang, Te-Su, i 張特書. "Mechanical and Thermal Effects on Alveolar Bone by Using Simplified Drilling Sequence". Thesis, 2017. http://ndltd.ncl.edu.tw/handle/369te5.
Pełny tekst źródła國立臺北科技大學
製造科技研究所
105
Simplified drilling sequence which reducing the number of drills used in alveolar bone drilling in dental implant surgery has become a trend for the past few years. It is hoped that the simplified drilling sequence can reduce the surgery time but on the other hand the surgical difficulty and bone damage may also arise. In this study, the mechanical and thermal effects of three simplified sequences were investigated by using finite element analysis combining failure theory and heat transfer module, and the effects of different drill parameters were also investigated using parametric finite element analysis. In the verification experiment, the correlations between the drilling experiment test results and finite element analysis results of conventional sequence showed high to intermediate correlation level. The three simplified drilling sequences were divided into “one twist drill” (S1), “equal drill diameter increase” (S2) and “equal drilling cross-sectional area increase” (S3). In the parametric analysis of drill parameters, only the final drill model of conventional sequence was used to investigate the influences of friction coefficient and drill density. The drilling condition used in all analysis groups were, feed rate: 1 mm/s, cutting speed: 800 rpm, cutting depth: 10 mm and initial temperature: 25°C. The axial cutting reaction force, axial cutting torque and temperature change at depths of 3, 6, and 9 mm and distance of 1 mm from the hole wall were recorded in both experiment and analysis. The results showed that the conventional sequence had less thermal damage and breakage risk but the surgery time may be longer. Although the chances for drilling modification may be more for traditional sequence, however, the bone-implant interface may be less ideal. On the other hand, the simplified drilling sequences were found to have opposite effects when compared to the conventional drilling sequence. The simplified drilling group S2 and S3 can reduce the thermal damage as compared to sequence S1 where as sequence S3 has the least thermal damage. From the parametric analysis results, when reducing the friction coefficient could reduce the thermal damage. When all other parameters were set to be the same, higher drill density would result in more thermal damage. The results of this study can provide reference for dental drill manufacturers when developing new drill sets.
Chen, De Yuan, i 陳德元. "The mechanism of cytotoxic effect of aflatoxin B1 on swine alveolar macrophages". Thesis, 1995. http://ndltd.ncl.edu.tw/handle/68418342440549605964.
Pełny tekst źródłaScherbart, Agnes Martha [Verfasser]. "Mechanisms and consequences of particle uptake in alveolar macrophages / vorgelegt von Agnes Martha Scherbart". 2011. http://d-nb.info/101287852X/34.
Pełny tekst źródłaHsiao, Yu Chun, i 蕭宇君. "Mechanisms underlying TNF-a-induced cytosolic phospholipase A2 expression in human alveolar epithelial cells". Thesis, 2010. http://ndltd.ncl.edu.tw/handle/61557363805703977784.
Pełny tekst źródła長庚大學
生物醫學研究所
98
Human pulmonary alveolar epithelial cells play an important role in the proliferation, migration, and inflammatory processes in the respiratory system. Several factors have been shown to trigger the mechanisms for the pathologenesis of airway diseases including asthma and chronic obstructive pulmonary disease (COPD). Although the factors concerning about the increased incidence of inflammatory responses are well known, however, the intracellular signaling pathways involved in the expression of inflammatory proteins are not completely recognized. Elevated levels of pro-inflammatory cytokines such as tumor necrosis factor- (TNF-) have been found in the airway fluids, which may induce up-regulation of cytosolic phospholipase A2 (cPLA2) implicated in the pathogenesis of inflammatory diseases. Although TNF- has been reported to activate all of mitogen-activated protein kinases (MAPKs) including p42/p44 MAPK, p38 MAPK, and JNK/SAPK, and transactivation of growth factor receptors and PI3K/Akt, the relationship between the activation of these signaling pathways and expression of cPLA2 or other genes remains largely unknown in human alveolar epithelial cells (HPAEpiCs). Therefore, whether activation of these MAPKs, growth factor receptors and PI3K/Akt pathways by TNF- linked to cPLA2 expression is needed determining in HPAEpiCs. In addition, it is of interest that many of the genes regulated by MAPKs are dependent on NF-B, AP-1, and p300 for transcription. These transcription factors have also been shown to be involved in cPLA2 gene expression at the transcriptional level in various cell types. Western blot and Real-time RT-PCR showed that in HPAEpiCs, TNF-α induced cPLA2 mRNA and protein expression in a time-dependent manner, which were attenuated by pretreatment with the inhibitors of ROS (NAC, APO, DPI), PDGF receptor (AG1296), PI3K (Wortmannine), and MEK1/2 (PD98059) or transfection with siRNA of p42. These results suggest that PDGFR transactivation participates in cPLA2 expression induced by TNF-α. Accordingly, TNF-α-stimulated phosphorylation of p38 MAPK and JNK were inhibited by pretreatment with NAC, APO, or DPI. TNF- induced cPLA2 expression was blocked by the selective inhibitors of AP-1 (Tanshinone IIA) and NF-B (Bay11-7082). Moreover, TNF-α-stimulated cPLA2 promoter activity was blocked by these selective inhibitors. In this study we investigated the effect of TNF-α induced cPLA2 expression at the transcriptional and translational levels, which were mediated through three independent pathways. First, TNF-α activated Jak2-dependent PDGFR transactivation, PI3K/Akt, p42/p44 MAPK, and p300/c-Jun/c-Fos/ATF2/AP-1 signalung pathway in HPAEpiCs. Secand, TNF-α-stimulated TNFR1 induced association of TRAF2, ASK-1 and p47phox, which promoted recruitment with ROS production, p38 MAPK phosphorylation, JNK1/2 phosphorylation resulting in AP-1 activation and cPLA2 expression and PGE2 release. In addation, TNF-α-induced ROS production which promoted recrument with NIK, IKK resulting in NF-B activation and cPLA2 expression and PGE2 release. These results provide new insights into the mechanisms of TNF-α action which may be therapeutic value in lung diseases.
Korpi-Steiner, Nichole LaRhette. "Mechanisms of cytokine elaboration by human alveolar macrophages and bronchial epithelial cells following rhinovirus challenge". 2006. http://www.library.wisc.edu/databases/connect/dissertations.html.
Pełny tekst źródłaCho, Rou Ling, i 卓若羚. "Mechanisms Underlying Lipopolysaccharide Induced Inter-Cellular Adhesion Molecule-1 Expression in Human Pulmonary Alveolar Epithelial Cells". Thesis, 2012. http://ndltd.ncl.edu.tw/handle/75392927840317412406.
Pełny tekst źródła長庚大學
生物醫學研究所
100
Respiratory problems such as asthma and chronic obstructive pulmonary disease (COPD) had been concerned issue of human airway diseases. Lipopolysaccharide (LPS), a key component of the outer membranes of Gram-negative bacteria, plays an important role in the induction of adhesion molecules expression and reactive oxygen species (ROS) generation in airway inflammatory diseases. However, the mechanisms by which up-regulation of intercellular adhesion molecule-1 (ICAM-1) induced by LPS may contribute to inflammatory responses or exert as a host defense in respiratory diseases are not completely understood. Here, we investigated the mechanisms of LPS-induced ICAM-1 expression in human pulmonary alveolar epithelial cells (HPAEpiCs). We found that LPS induced ICAM-1 protein and mRNA expression, promoter activity, and the adhesion of THP-1 cells , as well as the phosphorylation of c-Src, PDGFR, EGFR, Akt, and p65, which were attenuated by pretreatment with an anti-TLR4 Ab or the inhibitor of MEK1/2 (U0126), JNK1/2 (SP600125), p38 MAPK (SB202190), c-Src (PP1), PDGFR (AG1296), EGFR (AG1478), PI3K (LY294002), NADPH oxidase [diphenylene iodonium chloride (DPI)], ROS (Edaravone), NF-B (Bay11-7082) or AP-1 (Tanshinone II A). LPS-induced TLR4, MyD88, TRAF6, c-Src, p47phox, and Rac-1 complex formation was revealed by immunoprecipitation using an anti-TRAF6 and antic-Src Ab, followed by Western blot against an anti-TLR4, anti-MyD88, anti-TRAF6, anti- p47phox, anti-Rac-1, or anti-c-Src Ab. These results demonstrated that LPS-induced ICAM-1 expression was mediated through TLR4/ MyD88/ TRAF6/ p47phox /Rac-1/ c-Src via EGFR, PDGFR/PI3K or MAPKs, in turn initiates NF-B activation, and ultimately induced ICAM-1 expression and the adhesion of THP-1 cells on HPAEpiCs. Moeover, in animal medol we also can find ICAM-1 expression and inflammation symptom.
Hsu, Chun Hao, i 許峻豪. "Mechanisms of sphingosine 1-phosphate-induced intercellular adhesion molecule-1 expression in human pulmonary alveolar epithelial cells". Thesis, 2013. http://ndltd.ncl.edu.tw/handle/26577587528000109277.
Pełny tekst źródła長庚大學
生物醫學研究所
101
Human pulmonary alveolar epithelial cells play an important role in the proliferation, migration, and inflammatory processes in the respiratory system. Several factors have been implicated to trigger the mechanisms for the pathologenesis of airway diseases including asthma and chronic obstructive pulmonary disease (COPD). Human pulmonary alveolar epithelial cells (HPAEpiCs) play an important role in airway inflammatory processes. Several studies demonstrate that expression of adhesive molecules on the cell surface of epithelial cells plays a critical role in these inflammatory responses. Although the factors concerning about the increased incidence of inflammatory responses are well known, however, the intracellular signaling pathways involved in the expression of inflammatory proteins are not completely recognized. Sphingosine 1-phosphate (S1P), one of the lipid components has attracted much attention as a possible signaling mediator that regulates immune responses and inflammatory processes in the respiratory system. Although S1P has been shown to activated MAPKs, PI3K/Akt, PTK and other signaling molecules up-regulation of ICAM-1 in various cell types, however, the mechanisms underlying S1P-induced ICAM-1 expression in HPAEpiCs remain unknown. Thus, this study is to investigate the signaling pathways implicated in S1P-induced ICAM-1 expression in these cells. Our hypothesis is that up-regulation of ICAM-1 induced by S1P may contribute to inflammatory responses or exert as a host defense in respiratory diseases. We found that S1P induced ICAM-1 protein and mRNA expression, promoter activity, and the adhesion of THP-1 cells , as well as the phosphorylation of c-Src, PDGFR, EGFR, p42/p44, p38, Jnk1/2, Akt, PKCδ, PYK2, NADPH oxidase, ROS, p65 and c-Jun, which were attenuated by pretreatment with an anti-S1PR1, anti-S1PR3 Ab or the inhibitor of c-Src (PP1), PDGFR (AG1296), EGFR (AG1478), Erk1/2 MAPK (U0126), Jnk1/2 (SP600125), p38 MAPK (SB202190), PI3K (LY294002), PKCδ (Rottlerin), PYK2 (PF431396), NADPH oxidase (APO, DPI), ROS (Edaravone), NF-kB (Bay11-7082) or c-Jun (Tashinone IIA). These results demonstrated that S1P-induced ICAM-1 expression was mediated through S1PR1, S1PR3/Gi &; Gq protein via c-Src/EGFR and PDGFR/p42/p44 and p38/PI3K/Akt, or PKCδ / PYK2 / NADPH / ROS in turn initiates NF-kB (p65) and AP-1 (c-Fos and c-Jun) activation, and ultimately induces ICAM-1 expression and the adhesion of THP-1 cells in HPAEpiCs.
Chen, Yi Wen, i 陳薏雯. "The mechanisms and anti-inflammatory effects of Kaempferol induced HO-1 expression in human pulmonary alveolar epithelial cells". Thesis, 2018. http://ndltd.ncl.edu.tw/handle/9askth.
Pełny tekst źródłaCHEN, HSIAO-MEI, i 陳筱玫. "Mechanisms Underlying Adiponectin–mediated Expression of Cytosolic Phospholipase A2 and Cyclooxygenase-2 in Human Pulmonary Alveolar Epithelial Cells". Thesis, 2014. http://ndltd.ncl.edu.tw/handle/22447606319406163983.
Pełny tekst źródła輔仁大學
基礎醫學研究所碩士班
102
Adiponectin is one of adipocyte-derived hormones. Regarding to reports, adiponectin has pro-inflammatory or anti-inflammatory effects in different organs. But in lung system, what the role of adiponectin is still not known. On the other hand, lung inflammation companied occurrence of various acute or chronic lung diseases, including chronic obstructive pulmonary disease, emphysema and idiopathic pulmonary fibrosis, acute respiratory distress syndrome and obstructive apnea. It is found that several genes such as cPLA2 and COX-2 express and cooperate mediating the occurrence and amplification of inflammatory responses. cPLA2 and COX-2 are up-regulated resulting in the increase of end-point product prostaglandins in response to the stimulation of exogenous stimuli or cytokines. However, it is not clear whether adiponectin contributes to lung diseases via modulating expression of cPLA2 and COX-2 and resulting in lung inflammation. Thus, in this work, how adiponectin regulated pulmonary inflammation and the related mechanisms will be established. Our hypothesis is that up-regulation of cPLA2 and COX-2 stimulated by adiponectin promote inflammatory responses in the lung. To addressing these questions, the experiments with pharmacological inhibitors were performed to investigate the roles of ROS, JAK/STAT, AMPK, PI3-K/Akt, Src and PKC in adiponectin-induced cPLA2 and COX-2 expression in lung alveolar type II cells. Several techniques such as Western blot, RT-PCR and cell fraction isolation assay were used to investigate the molecular interactions between signaling components. Our results proved that adiponectin induced cPLA2 and COX-2 expression throught adipoR1 and adipoR2. Moreover, pretreatment of N-acetyl-cysteine, rotenone, apocynin, Ro31-8220, Gö-6976, rottlerin, PP1, LY294002, wortmannin, BML-275, AG490, WP1066, STAT5 inhibitor, garcinol attenuated adiponectin-stimulated protein and mRNA expression of cPLA2 and COX-2. And adiponectin modulated accumulation of ROS and activation of mitochondria. Similarly, adiponectin regulated activation of PKC, c-Src, AMPK, JAK2 and STAT3. These results revealed that adiponectin-regualted expression of cPLA2 and COX-2 genes at least via AdipoR1, AdipoR2, ROS, mitochondria, NADPH oxidase, PKC, c-Src, PI3-K/AKT, AMPK, JAK/STAT and p300. These results will provide new insight into the mechanisms of adiponectin actions, supporting the hypothesis that adiponectin may contribute to inflammatory responses involved in the development of lung diseases. Increased understanding of signal transduction mechanisms underlying cPLA2 and COX-2 gene regulation will create opportunities for the development of anti-inflammation, anti-cancer and anti-metastasis therapeutic strategies.
Wu, Ming Yen, i 吳明諺. "Mechanisms of heat-killed Staphylococcus aureus-induced vascular cell adhesion molecule-1 expression in human pulmonary alveolar epithelial cells". Thesis, 2011. http://ndltd.ncl.edu.tw/handle/19976734201622663641.
Pełny tekst źródła長庚大學
生物醫學研究所
99
Staphlococcus aureus (S. aureus), the common Gram-positive bacteria, causes a wide range of human inflammatory diseases, such as asthma and chronic obstructive pulmonary disease (COPD). These inflammatory responses are mediated by complex interactions between both circulating polymorphonuclear cells (PMNs) and the vascular endothelium. Several studies have indicated that expression of adhesive molecules on the cell surface of epithelial cells plays a critical role in these inflammatory responses. Although S. aureus has been shown to induce ICAM-1 or VCAM-1 expression in various cell types, the mechanisms underlying S. aureus-induced VCAM-1 expression in human pulmonary alveolar epithelial cells (HPAEpiCs) remain unknown. Western blot, Real time-PCR, and monocytes adhesion analyses showed that in HPAEpiCs, S. aureus induced VCAM-1 mRNA and protein expression in a time-dependent manner, which were attenuated by the inhibitors of c-Src (PP1), PDGF receptor (AG1296), PI3K (LY294002), JNK (SP600125), p38 MAPK (SB202190), MEK1/2 (U0126), AP-1 (Tanshinone IIA), NF-kB (Bay11-7082) and p300 (GR343), or transfection with siRNA of TLR2, MyD88, p42, p38, JNK1, c-Src, PDGFR, Akt, p65, c-Jun, ATF2, p300. These results suggest that PDGFR transactivation participates in VCAM-1 expression induced by S. aureus. Accordingly, S. aureus-stimulated phosphorylation of Akt, p38 MAPK, JNK and ERK1/2 was inhibited by pretreatment with PP1, AG1296, LY294002, SP600125, SB202190 or U0126. Taken together, in this study we investigated the effect of S. aureus induced VCAM-1 expression at transcriptional and translational levels. S. aureus-stimulated TLR2 induced association of MyD88 and c-Src, which mediated through two pathways. First, S. aureus activated c-Src, PI3K/Akt, ERK1/2 and JNK1/2. Second, S. aureus activated dependent PDGFR transactivation, p38 and JNK1/2. The two pathways both linked to AP-1, NF-B and p300, and induced VCAM-1 expression which led to monocytes adhesion. These results provide new insight into the mechanisms of S. aureus action, supporting that S. aureus may contribute to promote inflammatory responses involved in the development of respiratory diseases. Increased understanding of signal transduction mechanisms underlying VCAM-1 gene regulation creates opportunities for the development of anti-inflammation therapeutic strategie.
Yeh, Yi Cheng, i 葉怡成. "Mechanisms underlying mevastatin-induced heme oxygenase-1 expression and its anti-inflammatory effects in human pulmonary alveolar epithelial cells". Thesis, 2014. http://ndltd.ncl.edu.tw/handle/29053723126283653161.
Pełny tekst źródłaCho, Rou Ling, i 卓若羚. "Mechanisms underlying rosiglitazone-induced heme oxygenase-1 expression and its anti-inflammatory effects in human pulmonary alveolar epithelial cells". Thesis, 2018. http://ndltd.ncl.edu.tw/handle/xtt5ma.
Pełny tekst źródłaKonrad, Christian. "Molecular analysis of insulin signaling mechanisms in Echinococcus multilocularis and their role in the host-parasite interaction in the alveolar echinococcosis". Doctoral thesis, 2007. https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-22636.
Pełny tekst źródłaDer orthologe Insulinrezeptor EmIR des Fuchsbandwurmes Echinococcus multilocularis weist signifikante strukturelle Homologie zum humanen Insulinrezeptor (HIR) auf. Es wurde schon seit geraumer Zeit vermutet, dass EmIR an den Mechanismen beteiligt sein könnte, die es dem Metacestoden Larvenstadium des Parasiten erlauben Insulin zu detektieren. In dieser Arbeit wurden die Effekte von Wirtsinsulin auf Echinococcus Metacestoden-Vesikel und die vermutete Interaktion zwischen EmIR und Insulin von Säugern mittels biochemischer und zellbiologischer experimenteller Ansätze untersucht. Die exogene Zugabe von humanem Insulin zu in vitro kultivierten Parasitenlarven hatte folgende Effekte: (i) das Überleben und das Wachstum des Parasiten wurde signifikant stimuliert; (ii) die DNA de novo Synthese in Echinococcus wurde induziert; (iii) die generelle Proteinphosphorylierung des Parasiten wurde beeinflusst; (iv) die Phosphorylierung der orthologen Erk-like MAP Kinase, EmMPK1, des Parasiten wurde spezifisch induziert. Diese Beobachtungen zeigen deutlich, dass Echinococcus Metacestoden-Vesikel exogenes Insulin des Wirtes detektieren können und dass dieses Insulin einen mitogenischen Effekt auf den Parasiten hat. Um zu untersuchen, ob diese Effekte durch EmIR vermittelt werden, wurden anti-EmIR Antikörper hergestellt und in biochemischen experimentellen Ansätzen und immunohistochemischen Analysen eingesetzt. Es konnte gezeigt werden, dass EmIR in der Germinalschicht des Parasiten expremiert wird, sowohl an der Oberfläche von Glykogen-Speicherzellen als auch von undifferenzierten Germinalzellen. Nach der Zugabe von exogenem Insulin konnte eine signifikante Zunahme der Phosphorylierung von EmIR festgestellt werden. Diese Stimulierung konnte durch die Zugabe eines spezifischen Inhibitors für Insulinrezeptor-ähnliche Tyrosinkinasen unterdrückt werden. Desweiteren konnte mittels der Expression eines chimären EmIR/HIR-Rezeptors, der die extrazelluläre Ligandenbindungsdomäne von EmIR enthielt, in HEK293 Zellen gezeigt werden, dass die Zugabe von exogenem Insulin eine spezifische Autophosphorylierung der Chimäre induziert. Diese Ergebnisse bezeugen die Fähigkeit von EmIR Insulin-abhängige Signale des Wirtes einerseits zu detektieren und andererseits an die Echinococcus Signalwege weiter zu leiten. Die Bedeutung von Insulin-Signalmechanismen für das Überleben und das Wachstum des Parasiten konnte durch in vitro Kultivierungsexperimente aufgezeigt werden. Die Zugabe eines Inhibitors spezifisch für Insulinrezeptor Tyrosinkinasen verursachte die Degradation und den Tod der Metacestoden-Vesikel. Basierend auf den dargelegten molekularen Daten bezüglich der Interaktion zwischen EmIR und Insulin von Säugern erscheint es sehr wahrscheinlich, dass der orthologe Insulinrezeptor des Parasiten die Effekte von Insulin auf das Wachstum des Parasiten vermittelt. Aus diesem Grund ist EmIR ein potentieller Kandidat für die Kommunikation zwischen Wirt und Parasiten mittels evolutionär konservierten Signalwegen. Die Signalmechanismen unterhalb von EmIR wurden in abschließenden Experimenten untersucht. Diese offenbarten deutliche Unterschiede in der Weiterleitung von Insulin induzierten Signalen zwischen Echinococcus und dem verwandten parasitären Zestoden Taenia solium. Diese Unterschiede könnten mit dem unterschiedlichen Organtropismus beider Arten in Verbindung stehen
Benchimol, Maxime. "Complicações pós e intra-operatórias na anestesia de bloqueio regional do nervo alveolar inferior". Master's thesis, 2021. http://hdl.handle.net/10284/9644.
Pełny tekst źródłaIntroduction: This narrative review examines articles of particular interest for anesthetic complications of the lower aleveolar nerve. Objectives: The objective of this narrative review is to determine how to approach anesthetic complications of the lower aleveolar nerve, treatment, prevention. Materials and Methods: The searches were carried out on the websites SCIELO, B-ON and PUB MED, using the following keywords: "anasthesia,lower alveolar complications", in order to gather and discuss as much information as possible on this topic. Results and Conclusions: The results obtained reveal the importance of recognizing the anatomy of the lower alveolar nerve and its involvement, the type of anesthetic techniques and material that can be used, thus being able to reduce the probability of intra- and post-anesthetic errors and complications. It should also recognize these complications if they occur and how to solve them.
Durbin, Adam. "Studies on Signal Transduction Mechanisms in Rhabdomyosarcoma". Thesis, 2010. http://hdl.handle.net/1807/24739.
Pełny tekst źródłaKonrad, Christian [Verfasser]. "Molecular analysis of insulin signaling mechanisms in Echinococcus multilocularis and their role in the host parasite interaction in the alveolar echinococcosis / vorgelegt von: Christian Konrad". 2007. http://d-nb.info/984834710/34.
Pełny tekst źródłaChuang, Chi-Yuan, i 莊淇源. "STUDY OF ACUTE LUNG INJURY: MOLECULAR MECHANISMS OF LIPOPOLYSACCHARIDE-INDUCED APOPTOTIC INSULTS AND REGULATION OF surfactant protein GENE EXPRESSION IN HUMAN ALVEOLAR EPITHELIAL TYPE II CELLS". Thesis, 2011. http://ndltd.ncl.edu.tw/handle/03097245032120426995.
Pełny tekst źródła臺北醫學大學
臨床醫學研究所
99
Lipopolysaccharide (LPS), a Gram-negative bacterial outer membrane component, is one of the major causes of septic shock with acute lung injury. Pulmonary alveolar epithelial type II cells have highly specialized functions for synthesizing and secreting surfactant proteins (SPs) to participate in the physiological and pathophysiological regulation of sepsis-induced acute lung injury. Alterations in the levels of surfactant components in the lungs during inflammation are quite complex. Toll-like receptors (TLRs) that play important roles in innate immunity can transduce pathogen-triggered signals to regulate certain inflammation-related gene expressions through the activation of transcription factors. In contrast to low concentration of LPS-induced physical activity, intratracheal instillation of a high concentration of LPS in mice directly caused the death of bronchial epithelial cells. Thus, LPS may have pathophysiological and toxic effects on affecting the alveolar type II epithelial cells. The purpose of this research was aimed to evaluate the molecular mechanisms of LPS-induced cell apoptosis and surfactant proteins biosynthesis using human lung carcinoma type II epithelium-like A549 cells as the experimental model. Firstly, the study was aimed to evaluate the apoptotic effect of toxic concentration of LPS in A549 cells and the possible mechanisms. Exposure of A549 cells to clinical concentration (1~10 ng/ml) of LPS did not affect cell viability, but toxic dose (1~10 μg/ml) of LPS decreased cell viability in concentration- and time-dependent manners. In parallel, LPS concentration- and time-dependently induced apoptosis of A549 cells. LPS only at a high concentration of 10 μg/ml caused mildly necrotic insults to A549 cells. Exposure of A549 cells to LPS increased the levels of cellular nitric oxide and reactive oxygen species (ROS). Pretreatment with N-acetylcysteine, an antioxidant, significantly lowered LPS-caused enhancement of intracellular ROS in A549 cells and simultaneously attenuated the apoptotic insults. Treatment of A549 cells with LPS caused significant decreases in the mitochondrial membrane potential and biosynthesis of adenosine triphosphate. LPS triggered the release of cytochrome c from the mitochondria to the cytoplasm. Activities of caspases-9 and -6 were augmented following LPS administration. Consequently, exposure of A549 cells to LPS induced DNA fragmentation in a time-dependent manner. Pretreatment of A549 cells with N-acetylcysteine significantly ameliorated LPS-caused alterations in caspase-9 activation and DNA damage. Secondly, we attempted to evaluate the signal-transducing mechanisms of LPS-caused regulation of SP-A biosynthesis in A549 cells. Exposure of A549 cells to clinical concentration (1 ng/ml) of LPS increased SP-A protein and mRNA production in concentration- and time-dependent manners without affecting SP-D mRNA production. Clinical concentration of LPS time- dependently induced TLR2 mRNA expression and increased phosphorylation of mitogen-activated protein kinase (MEK) 4 & c-Jun NH2 terminal kinase 1 (JNK1) and augmented the translocation of c-Jun from the cytoplasm to nuclei without affecting c-Fos. Application of TLR2 small interference (si)RNA into A549 cells decreased the levels of this receptor and simultaneously inhibited LPS-induced SP-A mRNA and protein syntheses. After knocking-down the translation of MyD88 by RNA interference, the LPS-triggered MEK4 phosphorylation was attenuated. Application of TLR2 siRNA decreased LPS-enhanced phosphorylation of MEK4 and JNK1. Pretreatment of A549 cells with SP600125, an inhibitor of JNK1, significantly lowered LPS-induced c-Jun translocation and SP-A mRNA production. Taken together, this study has shown that toxic concentration of LPS specifically induces apoptotic insults to human alveolar epithelial cells through ROS-mediated activation of the intrinsic mitochondrion-cytochrome c-caspase protease mechanism and clinical concentration of LPS selectively induces SP-A gene expression possibly through TLR2-mediated sequential activation of MyD88-MEK4-JNK1-AP-1 in human alveolar epithelial A549 cells The LPS-induced apoptosis and sp-a gene expression in alveolar epithelial type II cells can indicate the status of Gram-negative bacteria-caused septic shock and acute lung injury. There are certain limitations in the present study, including A549 cells are derived from human lung carcinoma. The mechanisms of LPS-induced oxidative stress, cell apoptosis and production of SPs in A549 cells may be different from normal alveolar epithelial cells. In future studies, we will perform translational study to evaluate the signal-transducing effects of LPS on alveolar epithelial cells of animals and broncho-alveolar lavages with acute lung injury to validate our in vitro data.
Tan, Ju Jing. "Mechanosensitive ATP release in the lungs". Thesis, 2019. http://hdl.handle.net/1866/24849.
Pełny tekst źródłaATP is widely known to be an energy carrier within cells, but outside of the cell, it acts as an extracellular signaling molecule. Upon binding to purinergic receptors, extracellular ATP initiates the purinergic signaling to regulate certain physiological and pathophysiological processes. In the lungs, ATP stimulates surfactant secretion and promotes mucociliary clearance. Given the critical role of extracellular ATP in the lungs, it is important to understand the mechanism of cellular ATP release — the first step of purinergic signaling. Because mechanical forces constitute the primary trigger of ATP release, this thesis aims to investigate the physiological mechanism(s) and cellular sources of such mechanosensitive ATP release. This work is divided into three parts: 1) To study the spatial and temporal characteristics of ATP release, I developed a highly sensitive imaging technique based on luciferin-luciferase bioluminescence coupled with a custom-designed lens system, which combined a wide field of view (WFOV) and high light-gathering power. To evaluate our imaging approach, I subjected A549 cells, derived from human lung adenocarcinoma, to stretch or 50% hypotonic shock to trigger ATP release. I demonstrated that our technique allows us to precisely quantify the amount and the rate (or efflux) of ATP escaping from cells. The WFOV constitutes an essential tool used in the studies described in this thesis to determine the mechanism and cellular source of ATP release in the alveolus. 2) To examine the physiological mechanism of stretch-induced ATP release in primary alveolar cells, I determined the individual contributions of alveolar type 1 (AT1) in comparison with alveolar type 2 (AT2) cells. To this end, freshly isolated AT2 cells from rat lungs were seeded on a flexible silicone chamber and were cultured for up to seven days, which allowed AT2 cells to progressively transdifferentiate into AT1-like cells. The ratio of alveolar cells (AT2:AT1), being 4:1 on day 3, became 1:4 on day 7. The quantity of released ATP decreased with the decreasing numbers of AT2 cells, implicating them as the main source of ATP release in response to stretch. While pharmacological ATP channel modulators, carbenoxolone and probenecid, did not diminish the amount of ATP release, BAPTA, an intracellular calcium ([Ca2+]i) chelator, significantly reduced it. Likewise, these three modulators had similar effects on intracellular calcium responses measured by Fura-2, suggesting a connection between ATP release and [Ca2+]i levels. 3) To explore the role of membrane viscoelastic properties in mechanosensitive ATP release, I demonstrated that a 30% strain induced transient ATP release that was accompanied by uptake of propidium iodide (PI) in AT2 cells. This is consistent with a strain-induced transient membrane rupture, big enough for the passage of ATP and PI. ATP efflux also increases with strain rate, and hold time prolongs the half-life of ATP release. Thus, these results provide clues on how stretching of the viscoelastic membrane may lead to ATP release via an alternate mechanism involving transient mechanoporation of the cell membrane. Overall, these findings demonstrate that stretch-induced ATP release does not occur through ATP-conducting channels but rather a transient membrane mechanoporation. Further studies on membrane injury induced by strain are needed to better understand its contribution to mechanosensitive ATP release and [Ca2+]i signaling. Such studies will elucidate purinergic signaling in organs that are constantly exposed to physical stresses. This could suggest novel therapeutic targets/approach to modulate the negative impacts of excessive ATP release observed under certain pathological conditions, such as ventilator-induced lung injury.
Tabbaa, Chalabi Rajaa. "Effets des nanoparticules manufacturées sur les cellules pulmonaires humaines". Thèse, 2015. http://hdl.handle.net/1866/13674.
Pełny tekst źródłaDetection and characterization of manufactured nanoparticles (NPs) is one of the first steps to control and reduce potential risks to human health and the environment. Various sampling schemes in air exist for the evaluation of exposure to NPs. However, they do not measure the potential risk of this exposure to the human health and the cellular mechanisms that are responsible. Our research objectives are 1) To evaluate the effects of different types of nanoparticles on human lung cells and 2) Identify new intracellular mechanisms activated during exposure to various types of NPs. Methodology: The cell line A549 was used. Three types of NPs were studied (different concentrations and exposure time): titanium dioxide nanoparticles of anatase (TiO2), the simple wall carbon nanotubes (SWCN) and black carbon nanoparticles (BC). Cell viability was measured by the MTS assay, the PrestoBlue assay and the Trypan blue due exclusion test (only for the SWCN). To investigate whether the NPs stimulated ROS generation in A549 cels, the intracellular ROS level was measured using the DCFH-DA assay. The potential induction of oxidative stress responses in cells when exposed to TiO2 and SWCN was determined by the quantification of the extracellular levels of reduced (GSH) and oxidized glutathione (GSSG) forms. Results: The three nanoparticles do not appear to be toxic to A549 cells because there is a significant but small decrease in cell viability. However, they induce ROS production which is both time and concentration dependent. No change in the concentrations of GSH and GSSG were observed. In conclusion, our data indicate that measuring the cell viability is not a sufficient criterion for concluding if the NPs are toxic. ROS production is an interesting criterion, however, we have to demonstrate the activation of anti-oxidative systems to explain the absence of cell death following exposure to the NPs.