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Melatonin reduces oxidative stress and improves vascular function in pulmonary hypertensive newborn sheep 下载免费PDF全文
Flavio Torres Alejandro González‐Candia Camilo Montt Germán Ebensperger Magdalena Chubretovic María Serón‐Ferré Roberto V. Reyes Aníbal J. Llanos Emilio A. Herrera 《Journal of pineal research》2015,58(3):362-373
Pulmonary hypertension of the newborn (PHN) constitutes a critical condition with severe cardiovascular and neurological consequences. One of its main causes is hypoxia during gestation, and thus, it is a public health concern in populations living above 2500 m. Although some mechanisms are recognized, the pathophysiological facts that lead to PHN are not fully understood, which explains the lack of an effective treatment. Oxidative stress is one of the proposed mechanisms inducing pulmonary vascular dysfunction and PHN. Therefore, we assessed whether melatonin, a potent antioxidant, improves pulmonary vascular function. Twelve newborn sheep were gestated, born, and raised at 3600 meters. At 3 days old, lambs were catheterized and daily cardiovascular measurements were recorded. Lambs were divided into two groups, one received daily vehicle as control and another received daily melatonin (1 mg/kg/d), for 8 days. At 11 days old, lung tissue and small pulmonary arteries (SPA) were collected. Melatonin decreased pulmonary pressure and resistance for the first 3 days of treatment. Further, melatonin significantly improved the vasodilator function of SPA, enhancing the endothelial‐ and muscular‐dependent pathways. This was associated with an enhanced nitric oxide‐dependent and nitric oxide independent vasodilator components and with increased nitric oxide bioavailability in lung tissue. Further, melatonin reduced the pulmonary oxidative stress markers and increased enzymatic and nonenzymatic antioxidant capacity. Finally, these effects were associated with an increase of lumen diameter and a mild decrease in the wall of the pulmonary arteries. These outcomes support the use of melatonin as an adjuvant in the treatment for PHN. 相似文献
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Inflammation but not obesity or insulin resistance is associated with increased plasma fibroblast growth factor 23 concentration in the elderly 下载免费PDF全文
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Magdalena Cortes Alessandro Lambiase Marta Sacchetti Silvia Aronni Stefano Bonini 陈旭 《美国医学会眼科杂志(中文版)》2006,18(1):30-32
泪管-耳-牙-指(趾)(LADD)综合征是一种具有多种表现的常染色体显性遗传疾病。最初在1967年由Levy报道。1例双侧泪液系统缺失、杯状耳、干嘴,以及牙、手臂和指(趾)异常的单发病例。之后一些新发现的临床表现,如肾脏异常、唾液腺缺乏、先天性髋脱位、先天性裂孔疝和横膈疝、感觉性耳聋和传导性耳聋、牙发育不全、四肢异常、口腔干燥和眼干都被报道与此综合征有关。 相似文献
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Daniel P Potaczek Anetta Undas Magdalena Celinska-Lowenhoff Andrew Szczeklik 《Blood coagulation & fibrinolysis》2006,17(1):35-38
To evaluate whether the interleukin-6 (IL-6) -174 G/C polymorphism might alter the effects of micronized fenofibrate or simvastatin therapy on inflammatory markers, we measured IL-6, C-reactive protein, CD40 ligand, adhesion molecules, P-selectin and monocyte chemoattractant protein-1 in hypercholesterolemic patients both before and after a 30-day treatment. Serum IL-6 levels were significantly higher in patients with the GC or CC genotypes (P=0.04). The presence of the C allele was associated with greater absolute reduction of IL-6 levels (P=0.04) following fenofibrate treatment. There was no significant association between the -174 G/C IL-6 polymorphism and the effects of simvastatin treatment. A relationship between the -174 G/C IL-6 polymorphism and the anti-inflammatory action of fenofibrate reported might be useful in the optimization of the treatment regimen in patients receiving this class of drugs. 相似文献
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Marta Méndez-López Magdalena Méndez Fernando Sánchez-Patán Isabel Casado Maria-Angeles Aller Laudino López Maria-Teresa Corcuera Maria-Jose Alonso Maria-Paz Nava Jaime Arias Jorge-Luis Arias 《Journal of gastrointestinal surgery》2007,11(2):187-194
To obtain a new model of chronic portal hypertension in the rat, two classical methods to produce portal hypertension, partial portal vein ligation and the oral administration of thioacetamide (TAA), have been combined. Male Wistar rats were divided into four groups: 1 (control; n?=?10), 2 [triple partial portal vein ligation (TPVL); n?=?9], 3 (TAA; n?=?11), and 4 (TPVL plus TAA; n?=?9). After 3 months, portal pressure, types of portosystemic collateral circulation, laboratory hepatic function tests (aspartate aminotransferase, alanine aminotransferase, bilirubin, alkaline phosphatase, and gamma-glutamyl transpeptidase) and liver histology were studied. The animals belonging to group 2 (TPVL) developed extrahepatic portosystemic collateral circulation, associated with mesenteric venous vasculopathy without hepatic destructurization or portal hypertension. Animals from group 3 (TAA) developed cirrhosis and portal hypertension but not extrahepatic portosystemic collateral circulation, or mesenteric venous vasculopathy. Finally, the animals from group 4 (TPVL?+?TAA) developed cirrhosis, portal hypertension, portosystemic collateral circulation, and mesenteric venous vasculopathy. The association of TPVL and TAA can be used to obtain a model of chronic portal hypertension in the rat that includes all the alterations that patients with hepatic cirrhosis usually have. This could, therefore, prove to be a useful tool to study the pathophysiological mechanisms involved in these alterations. 相似文献
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E Flescher M J Dauphinée D Fossum J Ledbetter N Talal 《Arthritis and rheumatism》1992,35(9):1068-1074
OBJECTIVE. To study the effects of a novel A-type retrovirus, detected in cocultures of lip biopsy specimens from Sj?gren's syndrome (SS) patients and a human T cell line, on the infected T cells. METHODS. Interleukin-2 (IL-2) and IL-6 secretion were measured by bioassay and enzyme-linked immunosorbent assay, respectively, in the infected and noninfected cell lines. Surface antigen expression was determined by flow cytometry, using monoclonal antibodies. Protein kinase C (PKC) activity was measured using an enzyme assay kit, and calcium mobilization was assessed with a fluorescent probe. RESULTS. Infected cells expressed less CD4 and IL-6 receptor, but more HLA-DR, compared with noninfected cells. Infected cells also produced less IL-2 and displayed reduced PKC activation and calcium mobilization. A similar defect in calcium mobilization was detected in T cells from SS patients. CONCLUSION. These data suggest a possible involvement of the newly described retrovirus in T cell abnormalities. 相似文献