21 |
Participação de receptores ER e ER na ativação do eixo hipotálamo-hipófise-adrenal por estresse hemorrágico / Estrogen receptors ER and ER participation in HPA axis activation by hemorrhagic stressLuana Maria Silva Alves 11 August 2015 (has links)
Em função da categoria dos estressores, vias neurais específicas são envolvidas e respostas distintas podem ser induzidas. A literatura tem reportado que o estrógeno (E 2 ) através de seus receptores de tipos (ER) e (ER) influencia a atividade do eixo hipotálamo hipófise adrenal (HPA). Além disso, há evidências de que o E2 exerça efeitos protetores em situação de choque hemorrágico. O objetivo deste trabalho foi verificar a participação dos receptores ER e ER na atividade do eixo HPA durante estresse hemorrágico. Foram utilizadas ratas Wistar ovariectomizadas que receberam injeções s.c. de DMSO (veículo), PPT (agonista ER) ou DPN (agonista ER), durante 3 dias. No segundo dia, as ratas foram canuladas para coleta seriada de sangue na manhã seguinte. Os animais receberam (controle) ou não (hemorrágicos) reposição imediata com salina. Os hormônios corticosterona (CORT), ocitocina (OT) e vasopressina (AVP) foram dosados por radioimunoensaio. Ao final do experimento, os ratos foram perfundidos e os cérebros processados para imuno-histoquímica de FOS, tirosina hidroxilase (TH) e hormônio liberador de corticotrofina (CRH). Nos animais tratados com veículo, a hemorragia gradual moderada aumentou a secreção de CORT, OT e AVP, a expressão de neurônios TH ativados na região A1C1 e de FOS no mpPVN. O PPT reduziu a secreção de CORT, na situação controle atuando no LC e mpPVN; e também após hemorragia atuando no LC, NTS, A1C1 e mpPVN. O DPN reduziu a secreção de CORT apenas após estresse hemorrágico atuando no LC, A1C1 e mpPVN. O PPT bloqueou o aumento da secreção de OT e aumentou a secreção de AVP, após hemorragia. O DPN, por sua vez, reduziu a concentração plasmática de OT e aumentou a concentração plasmática de AVP, independentemente da hemorragia. Em conclusão: o estrógeno pode exercer uma ação inibitória sobre a secreção basal de CORT somente através da ação do ER sobre o LC e mpPVN; a secreção de CORT aumenta em resposta à hemorragia gradual moderada e o estrógeno pode exercer um controle inibitório nessa resposta através de ER atuando sobre LC, NTS, A1C1 e mpPVN, bem como através de ER atuando sobre LC, A1C1 e mpPVN. / Depending on the stressors category, specific neural pathways are involved and different responses can be selected. It has been reported in the literature that estrogen (E2 ) can affect hypothalamus pituitary adrenal (HPA) axis activity through its receptors type (ER) and (ER). Moreover, there is evidence that E 2 has protecting properties after hemorrhagic shock. The aim of this work was to assess the participation of ER and ER on HPA axis activity during hemorrhagic stress. It was used ovariectomized Wistar rats that received s.c. injections of: DMSO (vehicle), PPT (ER agonist) or DPN (ER agonist), during 3 days. In the second day the rats were catheterized for serial blood collect in the next morning. Animals received (control) or not (hemorrhagic) immediate reposition with same volume of isotonic saline. The hormones corticosterone (CORT), oxytocin (OT) and vasopressin (AVP) were measured by radioimmunoassay. At the end of the experiment, animals were perfused and their brains were processed for immuno-histochemistry for FOS, tyrosine hydroxylase (TH) and corticotropin releasing hormone (CRH). In vehicle treated animals, the gradual hemorrhage enhanced CORT, OT and AVP secretion, TH activated neurons expression in A1C1 and FOS expression in mpPVN. PPT decreased plasma CORT in control situation acting on LC and mpPVN, and also after hemorrhage acting on LC, NTS, A1C1 and mpPVN. DPN reduced plasma CORT only after hemorrhagic stress acting on LC, A1C1 and mpPVN. PPT blocked the increase of OT secretion and increased AVP secretion, after hemorrhage. The agonist DPN reduced OT and increased AVP levels, despite hemorrhage. In conclusion: E2 can exert an inhibitory effect on CORT basal secretion only through ER action on LC and mpPVN; CORT secretion increases after gradual moderate hemorrhage and E2 inhibit this secretion through ER action on LC, NTS, A1C1 and mpPVN, as well through ER action on LC, A1C1 and mpPVN.
|
22 |
Intracellular localization, biochemical and biophysical properties of human ArmetZhu, Xiaoxi January 1900 (has links)
Master of Science / Department of Biochemistry / Gerald R. Reeck / Armet is a bifunctional protein widely distributed in animal species, vertebrate and invertebrate. It is an evidently part of the Unfolded Protein Response (UPR) and promotes survival in cells that are under endoplasmic-reticulum (ER) stress. It has also been found as a secreted protein with neurotrophic activity. The crystal and solution structures of human Armet show it is a helix-rich protein with two domains linked through a flexible linker region. In this study, immunofluorescence staining was used to verify Armet’s localization in ER and Golgi apparatus in MBA-MD-231 cells. Evidence for calcium binding by Armet was obtained by circular dichroism spectroscopy (the binding of calcium appeared to decrease helix content), by differential scanning calorimetry (binding of calcium resulted in a less structured protein) and two-dimensional (1H-15N HSQC) nuclear magnetic resonance spectroscopy. A difference HSQC spectrum of Armet, with and without calcium, showed peaks of increased intensity, of decreased intensity and of perturbed chemical shift. There were about 30 such peaks in total. Several of these affected amino acid residues appeared to form a cluster of negatively charged side chains that could possibly form a binding site for a calcium ion. Heterogeneity of three types was observed in recombinant Armet expressed in E. coli cells. Two bands of slightly different mobility were observed in SDS gels run in the absence of reducing agent. These may represent alternate arrangements of disulfide bonds, as previously reported by other investigators but not explained. Further, in the absence of reducing agent, a faint ladder was formed by human Armet, indicating formation of disulfides between Armet molecules. Oligomers with sedimentation coefficient greater than the monomeric protein, in the absence of reducing agent, disappeared in the presence of a reducing agent. Finally, minor species of mass differences of 98 and 180 with respect to the main protein component were observed by MALDI-TOF mass spectrometry.
These studies provide a more thorough characterization of Armet than has been previously available and set the scene for future investigations of the binding of organic ligands to the protein.
|
23 |
Understanding molecular pathology of chondrodysplasias : the role of ER stressMularczyk, Ewa January 2012 (has links)
MCDS is an autosomal dominant disorder, with a mild dwarfed phenotype and is caused by mutations in collagen X. The majority of the mutations identified so far are localized almost exclusively within the NC1 domain, which is responsible for trimerization of the collagen X protein. Little is known about the onset of MCDS, but recently, up-regulation of ER stress has been suggested as an important mechanism promoting the MCDS phenotype. Several studies have shown that the mutated collagen X protein is retained within the ER triggering the UPR, which has proved to be the key pathway responsible for the pathogenesis of the MCDS phenotype. In order to study the consequences of the expressing the MCDS-causing COL10A1p.N617K mutation at the molecular level, we selected HeLa cells as an appropriate cell line for the characterisation of the UPR response, by showing that the three branches of the UPR can be activated by ER stress inducing conditions in a similar manner to that seen in vivo in the MCDS growth plate. Importantly we have also shown that HeLa cells can be transduced with the collagen X cDNA constructs and will express, fold and secrete collagen X into the supernatant.Having established the cellular model for MCDS studies we demonstrated for the first time direct evidence for the retention of mutant collagen X within the ER. Moreover, we demonstrated that the mutant collagen X was degraded via a proteasomal pathway. Nevertheless, the level of ER stress induced by expression of mutant collagen X, based on BiP induction at the protein level, was disappointingly low. We therefore directly compared the level of ER stress induced by the COL10A1p.N617K mutation with that of the chondrodysplasias-causing MATN3p.V194D mutation. The ER stress induced by the matrillin mutation was far greater than that caused by the mutant collagen X. We showed that general protein synthesis was reduced in cells expressing either of the mutant proteins, most likely by the mechanism associated with the phosphorylation of eIF2alpha. Moreover, we showed the mutant matrilin-3 protein was also retained specifically in the ER. However, we could find no evidence for either proteasomal or autophagic/lysosomal degradation of mutant matrilin 3.We tested a broad range of ER stress-relieving compounds on cells expressing mutant collagen X and matrilin 3. Carbamazepine, which was previously shown to reduce ER stress in alpha1-antitripsin deficiency, reduced ER stress in cells expressing the mutant collagen X (but not matrilin 3) by way of enhanced proteasomal degradation of the retained protein. This drug should now be tested in vivo against the MCDS mouse to determine its capacity to reduce disease severity.The results presented within this thesis have contributed to the understanding of how cells deal with mutant collagen X and matrilin-3 proteins. We have identified a potential therapeutic compound that may be of use in the treatment of MCDS. Furthermore, the data presented support the concept that generic approaches to relieving ER stress may not be suitable for treating a broad range of diseases. Treatments may need to be tailored not only in a gene-specific manner but also may need to be tailored to address the differing consequences of different mutations in the same gene.
|
24 |
Characterizing the Role of Stromal Cell Derived Factor 2 Like-1 (SDF2L1) in Pancreatic β-CellsTiwari, Akansha 20 December 2011 (has links)
Type 2 diabetes is characterized by insulin resistance and pancreatic β-cell failure. Insulin resistance leads to increased insulin demand, which can lead to increased proinsulin misfolding in the endoplasmic reticulum (ER). The accumulation of the misfolded proteins in the ER can cause ER stress, which can lead to pancreatic β-cell dysfunction. Cells respond to ER stress by the unfolded protein response (UPR), which increases protein folding capacity and causes degradation of misfolded proteins. Using a pancreatic β-cell model of induced misfolded proinsulin expression (proinsulin-C96Y tagged with GFP) we discovered that one of the most highly induced genes was stromal cell-derived factor 2 like 1 (SDF2L1). SDF2L1 is an ER localized soluble protein with an as yet unknown function. In this thesis I examined the potential role of SDF2L1 in pancreatic β-cells in ER stress conditions.
|
25 |
Characterizing the Role of Stromal Cell Derived Factor 2 Like-1 (SDF2L1) in Pancreatic β-CellsTiwari, Akansha 20 December 2011 (has links)
Type 2 diabetes is characterized by insulin resistance and pancreatic β-cell failure. Insulin resistance leads to increased insulin demand, which can lead to increased proinsulin misfolding in the endoplasmic reticulum (ER). The accumulation of the misfolded proteins in the ER can cause ER stress, which can lead to pancreatic β-cell dysfunction. Cells respond to ER stress by the unfolded protein response (UPR), which increases protein folding capacity and causes degradation of misfolded proteins. Using a pancreatic β-cell model of induced misfolded proinsulin expression (proinsulin-C96Y tagged with GFP) we discovered that one of the most highly induced genes was stromal cell-derived factor 2 like 1 (SDF2L1). SDF2L1 is an ER localized soluble protein with an as yet unknown function. In this thesis I examined the potential role of SDF2L1 in pancreatic β-cells in ER stress conditions.
|
26 |
Determination of polarization charge density on interface of AlGaN/GaN heterostructure by electroreflectanceWu, Chia-Chun 10 July 2006 (has links)
Electroreflectance spectra of AlGaN/GaN heteostructure were measured for various biased voltage (Vbias). There are Franz-Keldysh oscillations (FKOs) exhibiting above band gap of AlGaN, and strength of electric field of AlGaN (FAlGaN) can be evaluated from periods of the FKOs. A positive polarization charge
|
27 |
Avaliação do Uso do Laser Er:Yag no Tratamento da Osteonecrose Mandibular Induzida por Bisfosfonatos: estudo experimental em ratos.Melo, Marina Lins Maymone de 31 January 2014 (has links)
Submitted by Etelvina Domingos (etelvina.domingos@ufpe.br) on 2015-04-08T18:57:45Z
No. of bitstreams: 2
DISSERTAÇÃO Marina Lins Maymone de Melo.pdf: 897152 bytes, checksum: bced8c7adc190105e134586fa6da3fec (MD5)
license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) / Made available in DSpace on 2015-04-08T18:57:45Z (GMT). No. of bitstreams: 2
DISSERTAÇÃO Marina Lins Maymone de Melo.pdf: 897152 bytes, checksum: bced8c7adc190105e134586fa6da3fec (MD5)
license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5)
Previous issue date: 2014 / REUNI-UFPE / O objetivo deste estudo foi comparar, em modelo animal, o tratamento da osteonecrose dos maxilares induzida por bisfosfonatos (OMIB) realizado por cirurgia com laser Er:YAG com a cirurgia convencional. Foi realizado um estudo controlado experimental in vivo, utilizando 12 ratos Wistar machos, divididos em três grupos: controle (C), cirurgia convencional (CONV) e cirurgia a laser (LAS). Os animais foram tratados por 12 semanas com uma injeção intra-peritoneal semanal utilizando soro fisiológico na dosagem de 0,1ml/100g (grupo C) ou ácido zoledrônico (ZA) com doses de 0,15mg/Kg (grupos CONV e LAS). Os animais foram submetidos a exodontia de primeiro e segundo molares mandibulares para indução da OMIB, e então tratados com curetagem (grupo CONV) ou ablação a laser de Er:YAG (grupo LAS). Após a eutanásia, as mandíbulas foram removidas, fixadas em formol a 10% e analisadas através microtomografia computadorizada (microCT) para avaliação do padrão de trabeculado e densidade óssea. Os espécimes foram então processados e corados em HE para avaliação microscópica.A análise das imagens do microCT mostrou presença de sequestros ósseos, com aumento dos espaços medulares do osso esponjoso no grupo CONV. O trabeculado do grupo LAS apresentou padrão semelhante ao grupo C. A densidade óssea não apresentou diferença estatisticamente significante entre os grupos. A análise microscópica evidenciou reparo ósseo alveolar avançado (acima de 60%) em todos os animais do grupo C e 75% do grupo LAS, sendo ausente em 50% do grupo CONV. O laser de Er:YAG apresenta-se como uma importante estratégia terapêutica para o tratamento cirúrgico da OMIB, sendo superior à curetagem.
|
28 |
Untold Stories of the ER : Providing Care During the COVID-19 Pandemic as Narrated by Emergency Room Nurses in Toronto, Ontario, CanadaMarsh, Andrea 12 September 2022 (has links)
As the COVID-19 pandemic has taken hold of Toronto, Ontario, Canada, and the world, it has highlighted many challenges healthcare workers face. Those nurses working in the emergency room (ER), settings that are under normal circumstances unpredictable and acute, have been particularly affected. This research aimed to explore the stories ER nurses tell to describe their experiences of working during the COVID-19 pandemic in Toronto, Canada. Narrative methodology was used to understand the thoughts, feelings, and problems facing ER nurses. The research study includes the stories of three Toronto-based ER nurses who share their experiences of working during the COVID-19 pandemic. Participants were interviewed twice, and data was analysed using the three-dimensional narrative inquiry space of time, sociality, and place. Plotlines of 'before they were heroes', 'hero', 'fall from grace', 'villain' and 'to be continued', organized each story. Resounding narrative threads emerged across the three narrative accounts and are presented as understandings. Threads that resonated across the stories include mistrust in leadership, fear and isolation, expectations and duty to care, nursing shortages, personal safety and PPE, workload and stress, moral and psychological distress, and lost voice. The findings of this inquiry offer a new context for understanding the thoughts, feelings, and problems facing ER nurses working in Toronto during the COVID-19 pandemic in a way that preserves, values, and respects the voices and stories of the nurses themselves, thus allowing for emotional healing while offering insight for nursing education, practice, and research.
|
29 |
Bcl-2-associated athanogene-1 (BAG-1) Modulates the Endoplasmic Reticulum Stress Response in ChondrocytesYang, Ling 01 May 2007 (has links)
No description available.
|
30 |
The Study of the High Frame Rate Imaging Method and Its Application to the Strain and Strain Rate ImagingChen, Hong 26 June 2012 (has links)
No description available.
|
Page generated in 0.0169 seconds