6,785 research outputs found
The effect of metabolic imbalance in the retina and beyond: new insights from the role of antioxidants, thyroid hormones and β3-adrenoceptor
No full textThe study of the molecular mechanisms underlying the pathological processes induced by metabolic imbalance could provide important insights for the development of novel therapeutic strategies to counteract the onset of diseases in particularly sensitive tissues. The high energy demand required by retinal neurons renders them highly susceptible to various metabolic stressors, inducing imbalanced metabolism-related pathological processes such as oxidative stress and inflammation, then triggering neurodegenerative phenomena and loss of visual function. Thus, an overall improvement in the retinal components altered by hyperglycemia could be achieved by preventing the onset of oxidative stress induced by metabolic imbalance. In this context, the role of the thyroid hormone (TH) and β-adrenergic systems in response to metabolic imbalances, including changes in oxygen and glucose levels, was investigated in dysfunctional retinas, given the central role of the TH system in metabolic regulation and the predominant expression of β3-adrenoceptor (β3-AR) in the retinal vasculature. In addition, the systemic role of β3-AR was investigated in the potential cross-talk between adipose tissue and the heart, given the close correlation between altered adipose tissue and increased risk of cardiovascular disease onset and the maximal expression of β3-AR in adipose tissue, where it plays a pivotal role in regulating metabolic processes reflected in a modulation of the overall metabolic state. Therefore, this thesis is focused on providing further insights into the molecular mechanisms underlying dysfunctional metabolism-driven pathological processes in retinal diseases, suggesting possible new therapeutic approaches aimed at preventing or counteracting retinal neurovascular alterations and related loss of visual functions. Moreover, the preliminary study on the putative role of β3-AR in the adipose tissue-heart communication provides initial evidence for potential new therapeutic strategies using β3-AR agonism in adipose tissue as an additional cardioprotective effect to counteract the pathological signs of heart failure induced by obesity. In particular, the effects of oral administration of a natural compound with pronounced antioxidant and anti-inflammatory properties, including cyanidin-3-glucoside (C3G), verbascoside and zinc, were first evaluated in a rat model of streptozotocin (STZ)-induced diabetic retinopathy (DR), considering oxidative stress and related inflammation as the metabolic dysfunction-induced upstream processes that promote neurovascular alterations typical of DR. In this model, the compound demonstrated efficacy in counteracting oxidative stress and inflammatory processes, thereby preventing hyperglycemia-induced neurovascular alterations, including BRB dysfunction, retinal cell degeneration and visual loss. Hence, the beneficial effects displayed by the oral administration of the compound in preventing oxidative stress and inflammation suggested a possible new non-invasive treatment for DR. Furthermore, a putative retinal modulation of thyroid hormone (THs) levels in response to hyperglycemic-related stress was evaluated in 16-week-old db/db mice, due to their genetic background-related spontaneous development of T2DM and obesity state. In response to high glucose exposure, a retinal low-T3 state (LT3S) was shown as a local adaptive mechanism against the persistent increase in metabolic rate. Therefore, the LT3S onset suggested an early retinal response to hyperglycemic stress, although it could turn detrimental in the long term exacerbating mitochondrial dysfunction and related retinal energetic failure. Additionally, a putative molecular mechanism involving the activation of the Nrf2/HIF-1 axis in response to hyperglycemia-induced oxidative stress was investigated in the human MIO-M1 cell line. Together, these findings would demonstrate a retinal response against hyperglycemic stress in the early stages of DR, in which oxidative stress-related pathways are crucial for the LT3S onset, thus suggesting the pivotal involvement of the TH system even in the retinal metabolic regulation and providing further insights regarding possible therapeutic strategies for DR. The effect of β3-AR agonism was first investigated using the oxygen-induced retinopathy (OIR) mouse model, given its predominant localization in the retinal vasculature. Being more susceptible to hypoxia-induced pathological angiogenesis and showing higher β3-AR expression than other mouse strains, 129S mice were used in this study to better reproduce the typical hallmarks of preterm infant immature retinas affected by retinopathy of prematurity (ROP). In this respect, β3-AR agonism with BRL 37344 showed an efficacy in counteracting the OIR-induced neurovascular alterations, preventing vascular and astrocyte template regression in the central retina, mid-peripheral engorged tuft formation, retinal ganglion cells (RGCs) degeneration and vision loss. Therefore, pharmacological modulation of β3-AR activity could offer novel insights into therapeutic strategies aimed at counteracting pathological OIR-induced retinal angiogenesis. In order to evaluate the systemic role of β3-AR in a condition of dysregulated metabolism induced by obesity, the effects of β3-AR agonism, delivered by CL 316,243-releasing osmotic mini-pumps, were studied in 12-week-old C57BL/6J mice fed a diet enriched in fat and sugar for 28 weeks to mimic the major pathological signs of cardiac and white adipose tissue (WAT) dysfunction. β3-AR agonism showed efficacy in maintaining glucose and insulin tolerance, as well as preventing obesogenic diet-induced cardiac hypertrophy and interstitial fibrosis. In addition, reduced immune cell proliferation and upregulated metabolic markers typical of brown adipose tissue (BAT) suggested a β3-AR-mediated anti-inflammatory and ‘beiging’ effect in WAT, previously associated with a beneficial effect on overall metabolic status, providing first indications of a potential new therapeutic approach based on the systemic β3-AR-mediated effects in the prevention of the obesity-induced cardiovascular alterations through adipose tissue-heart communication. Taken together, these findings provide new insights into the molecular mechanisms involved in metabolically induced retinal and cardiac diseases, thus suggesting potential new therapeutic approaches aimed at counteracting the onset of pathological processes induced by metabolic dysfunction and the progression of related diseases
Restored retinal physiology after administration of niacin with citicoline in a mouse model of hypertensive glaucoma
No full textIntroduction: Much interest has been addressed to antioxidant dietary supplements that are known to lower the risk of developing glaucoma or delay its progression. Among them, niacin and citicoline protect retinal ganglion cells (RGCs) from degeneration by targeting mitochondria, though at different levels. A well-established mouse model of RGC degeneration induced by experimental intraocular pressure (IOP) elevation was used to investigate whether a novel combination of niacin/citicoline has better efficacy over each single component in preserving RGC health in response to IOP increase. Methods: Ocular hypertension was induced by an intracameral injection of methylcellulose that clogs the trabecular meshwork. Electroretinography and immunohistochemistry were used to evaluate RGC function and density. Oxidative, inflammatory and apoptotic markers were evaluated by Western blot analysis. Results: The present results support an optimal efficacy of niacin with citicoline at their best dosage in preventing RGC loss. In fact, about 50% of RGCs were spared from death leading to improved electroretinographic responses to flash and pattern stimulation. Upregulated levels of oxidative stress and inflammatory markers were also consistently reduced by almost 50% after niacin with citicoline thus providing a significant strength to the validity of their combination. Conclusion: Niacin combined with citicoline is highly effective in restoring RGC physiology but its therapeutic potential needs to be further explored. In fact, the translation of the present compound to humans is limited by several factors including the mouse modeling, the higher doses of the supplements that are necessary to demonstrate their efficacy over a short follow up period and the scarce knowledge of their transport to the bloodstream and to the eventual target tissues in the eye
[Poesia] Três poemas de Alberto Secama
No full textThree poems by Alberto Secama. About the author: Alberto Secama is an Angolan poet who has poems published on many websites and on facebook:https://www.facebook.com/Xungurra/abouthttp://www.pordentrodaafrica.com/cultura/africa-em-verso-rio-kwanza-por-alberto-secamahttp://www.pordentrodaafrica.com/cultura/africa-em-verso-zong-por-alberto-secamahttp://www.pordentrodaafrica.com/cultura/coluna-africa-em-verso-o-sol-la-fora-por-alberto-secamaTres poemas de Alberto Secama. Sobre el autor: Alberto Secama es un poeta angoleño que tiene poemas publicados en varios sitios y en el facebook:https://www.facebook.com/Xungurra/abouthttp://www.pordentrodaafrica.com/cultura/africa-em-verso-rio-kwanza-por-alberto-secamahttp://www.pordentrodaafrica.com/cultura/africa-em-verso-zong-por-alberto-secamahttp://www.pordentrodaafrica.com/cultura/coluna-africa-em-verso-o-sol-la-fora-por-alberto-secamaTrês poemas de Alberto Secama. Sobre o autor: Alberto Secama é um poeta angolano que possui poemas publicados em vários sites e no facebook:https://www.facebook.com/Xungurra/abouthttp://www.pordentrodaafrica.com/cultura/africa-em-verso-rio-kwanza-por-alberto-secamahttp://www.pordentrodaafrica.com/cultura/africa-em-verso-zong-por-alberto-secamahttp://www.pordentrodaafrica.com/cultura/coluna-africa-em-verso-o-sol-la-fora-por-alberto-secam
Increased efficacy of dietary supplement containing wax ester-rich marine oil and xanthophylls in a mouse model of dry macular degeneration
No full textAge-related macular degeneration (AMD) is nowadays considered among the retinal diseases whose clinical management lacks established treatment approaches, mainly for its atrophic (dry) form. In this respect, the use of dietary patterns enriched in omega-3 and antioxidant xanthophylls has emerged as a promising approach to counteract dry AMD progression although the prophylactic potential of omega-3 of fish origin has been discussed. Whether enriched availability of omega-3 and xanthophylls may increase the effectiveness of diet supplementation in preventing dry AMD remains to be fully established. The present study aims at comparing the efficacy of an existing orally administered formulation based on lutein and fish oil, as a source of omega-3, with a novel formulation providing the combination of lutein and astaxanthin with Calanus oil (COil), which contains omega-3 together with their precursors policosanols. Using a mouse model of dry AMD based on subretinal injection of polyethylene glycol (PEG)-400, we assessed the comparative efficacy of both formulations on PEG-induced major hallmarks including oxidative stress, inflammation, glial reactivity and outer retinal thickness. Dietary supplementation with both mixtures has been found to exert a significant antioxidant and anti-inflammatory activity as reflected by the overall amelioration of the PEG-induced pathological hallmarks. Noteworthy, the formulation based on COil appeared to be more protective than the one based on fish oil, presumably because of the higher bioavailability of omega-3 in COil. These results support the use of dietary supplements combining omega-3 and xanthophylls in the prevention and treatment of AMD and suggest that the source of omega-3 might contribute to treatment efficacy
Agonism of β3-Adrenoceptors Inhibits Pathological Retinal Angiogenesis in the Model of Oxygen-Induced Retinopathy
No full textPurpose: In response to hypoxia, sympathetic fibers to the retina activate β-adrenoceptors (β-ARs) that play an important role in the regulation of vascular and neuronal functions. We investigated the role of β3-AR using the mouse model of oxygen-induced retinopathy (OIR). Methods: Mouse pups were exposed to 75% oxygen at postnatal day 7 (PD7) followed by a return to room air at PD12. The β3-AR preferential agonist BRL37344 was subcutaneously administered once daily at different times after the return to room air. At PD17, the OIR mice underwent flash and pattern electroretinogram. After sacrifice, retinal wholemounts were used for vessel staining or immunohistochemistry for astrocytes, Müller cells, or retinal ganglion cells (RGCs). In retinal homogenates, the levels of markers associated with neovascularization (NV), the blood-retinal barrier (BRB), or astrocytes were determined by western blot, and quantitative reverse-transcription polymerase chain reaction was used to assess β3-AR messenger. Administration of the β3-AR antagonist SR59230A was performed to verify BRL37344 selectivity. Results: β3-AR expression is upregulated in response to hypoxia, but its increase is prevented by BRL37344, which counteracts NV by inhibiting the pro-angiogenic pathway, activating the anti-angiogenic pathway, recovering BRB-associated markers, triggering nitric oxide production, and favoring revascularization of the central retina through recovered density of astrocytes that ultimately counteracts NV in the midperiphery. Vasculature rescue prevents dysfunctional retinal activity and counteracts OIR-associated retinal ganglion cell loss. Conclusions: β3-AR has emerged as a crucial intermediary in hypoxia-dependent NV, suggesting a role of β3-AR agonists in the treatment of proliferative retinopathies
Preventive Efficacy of an Antioxidant Compound on Blood Retinal Barrier Breakdown and Visual Dysfunction in Streptozotocin-Induced Diabetic Rats
No full text: In diabetic retinopathy (DR), high blood glucose drives chronic oxidative stress and inflammation that trigger alterations of the neurovascular balance finally resulting in vascular abnormalities and retinal cell death, which converge towards altered electroretinogram (ERG). In the last years, a growing body of preclinical evidence has suggested that nutrients with anti-inflammatory/antioxidant properties can be able to hamper DR progression since its very early stages. In the present study, we used a streptozotocin-induced rat model of DR, which mimics most aspects of the early stages of human DR, to test the preventive efficacy of a novel compound containing cyanidin-3-glucoside (C3G), verbascoside and zinc as nutrients with antioxidant and anti-inflammatory properties. Western blot, immunofluorescence and electroretinographic analyses demonstrated a dose-dependent inhibition of oxidative stress- and inflammation-related mechanisms, with a significant counterpart in preventing molecular mechanisms leading to DR-associated vasculopathy and its related retinal damage. Preventive efficacy of the compound on dysfunctional a- and b-waves was also demonstrated by electroretinography. The present demonstration that natural compounds, possibly as a consequence of vascular rescue following ameliorated oxidative stress and inflammation, may prevent the apoptotic cascade leading to ERG dysfunction, adds further relevance to the potential application of antioxidants as a preventive therapy to counteract DR progression
Orizzonti mantovani. Spunti e dinamiche paesaggistiche ne L'Illustrissimo di Alberto Cantoni
No full textIn the literary production of Alberto Cantoni, short story writer and novelist between the nineteenth and twentieth centuries, the novel L'Illustrissimo is highly important both because it is the last publication of the author, from Pomponesco, a small town a few kilometers south of Mantua, both because it summarizes in a single text the different nuances and different directions that his writing has taken over the course of his literary career, also due to a writing and processing time that embraces the entire span of years of his career itself. In the foreground, in addition to the numerous and brilliant characters, one of the protagonists is the Mantuan landscape which, not a simple background, becomes a true literary parameter which in different and significant ways affects the purposes and mechanisms of the novel
Plenary Session: Luis Alberto Urrea
No full texta) Plenary Session: Luis Alberto Urrea, Mexican American Chicago Writer
Luis Alberto Urrea is a 2005 Pulitzer Prize finalist for non-fiction and member of the Latino Literature Hall of Fame. He is a prolific and acclaimed writer who has used his dual-culture life border experiences to explore the complex and interconnected Mexican-US American reality. The critically acclaimed and best-selling Mexican-born author of 13 books, Urrea has won numerous awards for his poetry, fiction and essays.
Moderator: Dr. Héctor García, Loyola University Chicag
O duplo significado do sentir e do pensar nas obras de Alberto Caeiro e Descartes
No full textDissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Comunicação e Expressão. Programa de Pós-Graduação em LiteraturaA pretensão desta dissertação intitulada O duplo significado do sentir e do pensar nas obras de Alberto Caeiro e Descartes é investigar a relação entre o sentir e o puro pensar, usando como referência a poesia O Guardador de Rebanhos, de Alberto Caeiro, que apresenta de forma evidente o tema; e como este assunto é tratado nas Meditações Metafísicas de René Descartes, também de forma claramente visível. Podemos perceber em ambos os autores, uma diplopia, uma espécie de duplo olhar sobre a relação sentir e puro pensar. No primeiro capítulo vou falar sobre a tese do duplo olhar de Descartes, a respeito da relação sentir e puro pensar na leitura de Merleau-Ponty, salientando a visão de natureza. No segundo capítulo, parto da leitura das três primeiras Meditações Metafísicas para caracterizar a tensão que se pode verificar entre Descartes e Alberto Caeiro quando se referem ao puro pensar. O foco principal de Descartes, nas três primeiras Meditações, é o pensar puro, e neste ponto Alberto Caeiro critica o pensar puro. No terceiro capítulo, analisando as três últimas Meditações, percebe-se que há uma virada no pensamento de Descartes, no qual o autor inverte seu ponto de vista, aproximando-se da idéia de Alberto Caeiro. No quarto capítulo, mostrarei a leitura que outros autores fazem acerca do sentir e do pensar na obra de Alberto Caeiro, mostrando que assim como Descartes, este também ostenta uma diplopia, não do sentir, mas do pensar. The pretension of this work entitled O duplo significado do sentir e do pensar nas obras de Alberto Caeiro e Descartes is to investigate the relationship between the feeling and the pure thinking, using as reference the poetry O Guardador de Rebanhos, by Alberto Caeiro, that presents in an evident way this theme; and as this subject is treated in René Descartes' Metaphysical Meditations, also in a clearly visible way. It is possible to notice in both authors, the diplopy, a sort of double look about the relationship between feeling and pure thinking. The thesis about Descartes'double look regarding the relation of feeling and pure thinking, in Merleau-Ponty reading, pointing out the nature vision, will be treated in the first chapter. In the second chapter, I start from the reading of the first three Metaphysical Meditations to characterize the tension that can be verified between Descartes and Alberto Caeiro when they refer to the pure thinking. Descartes' main focus in the first three Meditations is pure thinking and, in this point, Alberto Caeiro criticizes pure thinking. In the third chapter, analyzing the last three Meditations, it is possible to notice that there is an alteration in Descartes' thought, in which the author inverts his point of view, approaching of Alberto Caeiro's idea. In the fourth chapter, I will show the reading that other authors do concerning feeling and thinking in Alberto Caeiro's work, showing that as well as Descartes, this also shows a diplopy, not of feeling, but of thinking
Lobbying for change as a new theory and practice of active citizenship: author interview with Alberto Alemanno
No full textDo you believe that lobbying is a vehicle for representing the interests of some rather than all, meaning its actors can never be a force for good? Alberto Alemanno, author of Lobbying for Change: Find Your Voice to Create a Better Society, might convince you of the contrary. This interview with Barbara Aubin, LSE Public Affairs, reflects on the importance of engaging with our political representatives, holding them accountable and lobbying for the causes we deeply care about as fundamental elements of a healthy democracy
- …
