732 research outputs found
Angiotensin II induces soluble fms-Like tyrosine kinase-1 release via calcineurin signaling pathway in pregnancy
Get PDFMaternal endothelial dysfunction in preeclampsia is associated with increased soluble fms-like tyrosine kinase-1 (sFlt-1), a circulating antagonist of vascular endothelial growth factor and placental growth factor. Angiotensin II (Ang II) is a potent vasoconstrictor that increases concomitant with sFlt-1 during pregnancy. Therefore, we speculated that Ang II may promote the expression of sFlt-1 in pregnancy. Here we report that infusion of Ang II significantly increases circulating levels of sFlt-1 in pregnant mice, thereby demonstrating that Ang II is a regulator of sFlt-1 secretion in vivo. Furthermore, Ang II stimulated sFlt-1 production in a dose- and time-dependent manner from human villous explants and cultured trophoblasts but not from endothelial cells, suggesting that trophoblasts are the primary source of sFlt-1 during pregnancy. As expected, Ang II-induced sFlt-1 secretion resulted in the inhibition of endothelial cell migration and in vitro tube formation. In vitro and in vivo studies with losartan, small interfering RNA specific for calcineurin and FK506 demonstrated that Ang II-mediated sFlt-1 release was via Ang II type 1 receptor activation and calcineurin signaling, respectively. These findings reveal a previously unrecognized regulatory role for Ang II on sFlt-1 expression in murine and human pregnancy and suggest that elevated sFlt-1 levels in preeclampsia may be caused by a dysregulation of the local renin/angiotensin system
Myxozoan pathogens in cultured Malaysian fishes. I. Myxozoan infections of the sutchi catfish Pangasius hypophthalmus in freshwater cage cultures
Get PDFCage-cultured sutchi catfish Pangasius hypophthalmus (Sauvage, 1878), a favourite food fish in Southeast Asia, proved to be infected by 6 myxozoan species. Three species belonged to the genus Hennegoides (H. berlandi, H. malayensis, and H. pangasii), 1 to Henneguya (H. shariffi) and 2 to Myxobolus (M. baskai, and M. pangasii). Five myxozoans infected the gills and 1 was found on the spleen. Myxozoans infecting the gills were characterised by a specific site selection. H. shariffi sp. n. and H. berlandi sp. n. formed plasmodia in the multi-layered epithelium of the gill filaments. Of the 2 vascular species H. pangasii sp. n. developed in the gin arteries, while M. baskai sp. n. infected the capillary network of the gill lamellae. Plasmodia of H. malayensis sp. n. were found inside the cartilaginous gill rays of the filaments. Large plasmodia of M. pangasii sp. n. were located in a groove of the spleen but they affected only the serosa layer covering the spleen
"I' ll tell you a story that will make you believe" in narratives: the role of metafiction in the novel and in the film Life of Pi
Get PDFDissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Comunicação e Expressão, Programa de Pós-Graduação em Inglês: Estudos Linguísticos e Literários, Florianópolis, 2015.Recentes estudos propõem que adaptações cinematográficas sejam entendidas como fonte de criação, os quais refletem contextos e interpretações diferentes do texto em que são baseadas. Nessa dissertação, propõe-se uma análise comparativa do romance Life of Pi (2001), de Yann Martel e do filme homônimo dirigido por Ang Lee (2012). A análise tem como objetivo identificar a presença e o modo em que a metaficção é construída no romance e no filme, e quais são alguns significados produzidos por ela em ambos os textos, tanto o literário quanto o fílmico. A concepção de metafição se baseia nas definições de Linda Hutcheon e Patricia Waugh. Por metaficção, entende-se a ficção consciente de si, que expõe o processo de escrita ao leitor e o convida a ter um papel ativo na construção do significado. Após uma análise comparativa dos dois textos, conclui-se que a metaficção está presente em ambos, tanto tematicamente como estruturalmente. As reflexões sobre narrativas apresentadas pelos personagens, o uso de vários níveis narrativos e de intertextualidade revelam diferentes usos da metafição em ambos. A diferença mais importante entre o romance e o filme Life of Pi está no uso dos níveis narrativos. Enquanto o romance possui um ?autor? sem nome que apresenta a história aos leitores, o filme possui um diretor implícito que deixa pistas de qual versão da história de Pi é ?real? no contexto da narrativa. Essa diferença dá ao romance um final aberto, em que o leitor deve escolher qual versão da história ele acredita, enquanto o filme possui uma resolução para essa questão. O filme, então, pode ser entendido como um testemunho, uma narrativa de trauma de um sobrevivente de um naufrágio e da experiência de migração, enquanto o livro não apresenta uma decisão em relação às versões da história, deixando o leitor aberto a qualquer possibilidade.Abstract : Recent studies propose that Film Adaptations should be understood as sources of creation, which also reflect a different context and interpretation from the text upon which they were based. In this thesis, I propose a comparative analysis of the novel Life of Pi (2001), by Yann Martel, and the homonymous film directed by Ang Lee (2012). The analysis has the objective of identifying the presence and the way in which metafiction is constructed in the novel and in the film, and what are some of the meanings produced by it in both texts, the filmic and the literary. The concept of metafiction was based on the definitions by Linda Hutcheon and Patricia Waugh. It is understood as the self-conscious fictional text, which exposes the writing process to the readers and invites them to have an active role in the construction of meaning. In the comparative analyses of the two texts, I have proved that metafiction is present in the two texts, both thematically and structurally. The reflections of the characters on narrative itself as well as the use of different narrative levels and intertextual references reveal different uses of metanarrative in both film and novel. The most important difference between the novel and the film Life of Pi is in their uses of different narrative levels. While the novel has an unnamed =author? who presents the story to the readers, the film has an implicit director who leaves =clues? of which version of Pi?s story is ?real? in the context of the narrative. This difference gives to the novel an open end, facein which the readers must choose which version of the story they believe in, while the film presents a resolution to this question. The film, thus, can be understood as a testimony narrative, a narrative of the trauma of a survivor from a shipwreck and from the experience of migration, while the novel does not decide for one of the versions of the story, enabling a more inconclusive reading
Regulation of muscle satellite cell activation and chemotaxis by angiotensin II.
No full textThe role of angiotensin II (Ang II) in skeletal muscle is poorly understood. We report that pharmacological inhibition of Ang II signaling or ablation of the AT1a receptor significantly impaired skeletal muscle growth following myotrauma, in vivo, likely due to impaired satellite cell activation and chemotaxis. In vitro experiments demonstrated that Ang II treatment activated quiescent myoblasts as evidenced by the upregulation of myogenic regulatory factors, increased number of β-gal+, Myf5-LacZ myoblasts and the acquisition of cellular motility. Furthermore, exogenous treatment with Ang II significantly increased the chemotactic capacity of C2C12 and primary cells while AT1a(-/-) myoblasts demonstrated a severe impairment in basal migration and were not responsive to Ang II treatment. Additionally, Ang II interacted with myoblasts in a paracrine-mediated fashion as 4 h of cyclic mechanical stimulation resulted in Ang II-induced migration of cocultured myoblasts. Ang II-induced chemotaxis appeared to be regulated by multiple mechanisms including reorganization of the actin cytoskeleton and augmentation of MMP2 activity. Collectively, these results highlight a novel role for Ang II and ACE inhibitors in the regulation of skeletal muscle growth and satellite cell function
Autologous Serum–Derived Cultivated Oral Epithelial Transplants for Severe Ocular Surface Disease
No full textAbsence of vascular remodelling in a high angiotensin-II state (Bartter's and Gitelman's syndromes): Implications for angiotensin II signalling pathways
No full textBackground. Angiotensin II (Ang II) is a powerful proinflammatory cytokine and growth factor that activates NF-κB, as well as NAD(P)H oxidase, and thus is a key factor for the induction and progression of cardiovascular diseases. Our previous studies have shown high Ang II and high blood pressure-driven proatherogenic remodelling in an animal model. To further explore Ang II in proatherogenic vascular remodelling independent of blood pressure, we used Bartter's/Gitelman's syndrome (BS/GS) patients given their elevated plasma Ang II, yet normo/hypotension, because extensive mechanistic studies in these patients suggest they are a good model to explore Ang II-mediated signalling. Methods. The study evaluated BS/GS patients for nitric oxide-dependent (FMD) and -independent vasodilation and intima-media thickness (IMT) of the carotid arteries compared with healthy subjects and essential hypertensive patients. Results. The results showed the absence of IMT growth in BS/GS patients as cumulative mean-IMT and mean maximum-IMT levels in BS/GS did not differ from normotensives: 0.58 ± 0.09 mm versus 0.60 ± 0.09 and 0.67 ± 0.09 versus 0.70 ± 0.13 respectively, P = ns, but were significantly lower compared with hypertensive patients: 0.69 ± 0.13, P < 0.046 and 0.85 ± 0.19, P < 0.018, respectively. FMD was increased in BS/GS versus hypertensives or normotensive controls (10.8 ± 2.7% versus 6.5 ± 2.3 and 8.7 ± 1.9, P < 0.002 respectively) while endothelium-independent dilation did not differ (10.2 ± 3.6% versus 7.2 ± 1.9 and 8.2 ± 3.3, P = ns) between groups. Conclusions. Our study in BS/GS provides to our knowledge the first clinical data that point to a direct proatherogenic role for Ang II. However, because the data are derived from findings in BS/GS and therefore are indirect, further studies in this and other models using more direct approaches should be pursued to demonstrate a direct proatherogenic effect of Ang II as well as further studies on Ang II type 2 receptor (AT2R) signalling that the spectrum of findings of this and other studies indicate as involved in the lack of vascular remodelling. © The Author [2008]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
Potassium Intake Prevents the Induction of the Renin-Angiotensin System and Increases Medullary ACE2 and COX-2 in the Kidneys of Angiotensin II-Dependent Hypertensive Rats
No full textPublisher Copyright: © 2019 Gonzalez, Gallardo, Cespedes and Vio. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.In angiotensin II (Ang II)-dependent hypertensive rats there is an increased expression of proximal tubule angiotensinogen (AGT), collecting duct renin and angiotensin converting enzyme (ACE), which contributes to intratubular Ang II formation. Ang II acts on Ang II type 1 receptors promoting sodium retention and vasoconstriction. However concurrently, the ACE2-Ang-(1-7) axis and the expression of kallikrein and medullary prostaglandins counteract the effects of Ang II, promoting natriuresis and vasodilation. Human studies demonstrate that dietary potassium (K+) intake lowers blood pressure. In this report we evaluate the expression of AGT, ACE, medullary prorenin/renin, ACE2, kallikrein and cyclooxygenase-2 (COX-2) in Ang II-infused rats fed with high K+ diet (2%) for 14 days. Dietary K+ enhances diuresis in non-infused and in Ang II-infused rats. The rise in systolic blood pressure in Ang II-infused rats was attenuated by dietary K+. Ang II-infused rats showed increased renal protein levels of AGT, ACE and medullary prorenin and renin. This effect was attenuated in the Ang II + K+ group. Ang II infusion decreased ACE2 compared to the control group; however, K+ diet prevented this effect in the renal medulla. Furthermore, medullary COX-2 was dramatically induced by K+ diet in non-infused and in Ang II infused rats. Dietary K+ greatly increased kallikrein immunostaining in normotensive rats and in Ang II-hypertensive rats. These results indicate that a high K+ diet attenuates Ang II-dependent hypertension by preventing the induction of ACE, AGT and collecting duct renin and by enhancing medullary COX-2 and ACE2 protein expression in the kidney
NF-κB Signaling-Mediated Activation of WNK-SPAK-NKCC1 Cascade in Worsened Stroke Outcomes of Ang II-Hypertensive Mice
Get PDFThis is the author accepted manuscript. The final version is available from Lippincott, Williams & Wilkins via the DOI in this recordData availability: The data that support the findings of this study are available within the article and its Data Supplement.BACKGROUND: Worsened stroke outcomes with hypertension comorbidity are insensitive to blood pressure-lowering therapies. In an experimental stroke model with comorbid hypertension, we investigated causal roles of ang II (angiotensin II)-mediated stimulation of the brain WNK (with no lysine [K] kinases)-SPAK (STE20/SPS1-related proline/alanine-rich kinase)-NKCC1 (Na-K-Cl cotransporter) complex in worsened outcomes. METHODS: Saline- or ang II-infused C57BL/6J male mice underwent stroke induced by permanent occlusion of the distal branches of the middle cerebral artery. Mice were randomly assigned to receive either vehicle dimethyl sulfoxide/PBS (2 mL/kg body weight/day, IP), a novel SPAK inhibitor, 5-chloro-N-(5-chloro-4-((4-chlorophenyl)(cyano)methyl)-2-methylphenyl)-2-hydroxybenzamide (ZT-1a' 5 mg/kg per day, IP) or a NF-κB (nuclear factor-κB) inhibitor TAT-NBD (transactivator of transcription-NEMO-binding domain' 20 mg/kg per day, IP). Activation of brain NF-κB and WNK-SPAK-NKCC1 cascade as well as ischemic stroke outcomes were examined. RESULTS: Stroke triggered a 2- to 5-fold increase of WNK (isoforms 1, 2, 4), SPAK/OSR1 (oxidative stress-responsive kinase 1), and NKCC1 protein in the ang II-infused hypertensive mouse brains at 24 hours after stroke, which was associated with increased nuclear translocation of phospho-NF-κB protein in the cortical neurons (a Pearson correlation r of 0.77, P<0.005). The upregulation of WNK-SPAK-NKCC1 cascade proteins resulted from increased NF-κB recruitment on Wnk1, Wnk2, Wnk4, Spak, and Nkcc1 gene promoters and was attenuated by NF-κB inhibitor TAT-NBD. Poststroke administration of SPAK inhibitor ZT-1a significantly reduced WNK-SPAK-NKCC1 complex activation, brain lesion size, and neurological function deficits in the ang II-hypertensive mice without affecting blood pressure and cerebral blood flow. CONCLUSIONS: The ang II-induced stimulation of NF-κB transcriptional activity upregulates brain WNK-SPAK-NKCC1 cascade and contributes to worsened ischemic stroke outcomes, illustrating the brain WNK-SPAK-NKCC1 complex as a therapeutic target for stroke with comorbid hypertension.Veteran AffairsNational Institutes of Health (NIH)AH
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