985 resultados para mesothelioma, lysine acetyltransferase, epigenetics, MG 149, inflammation


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Inflammatory bowel diseases are characterized by a chronic clinical course of relapse and remission associated with self-destructive inflammation of the gastrointestinal tract. Active extracts from plants have emerged as natural potential candidates for its treatment. Abarema cochliacarpos (Gomes) Barneby & Grimes, Fabaceae (Barbatimão), is a native medicinal plant in to Brazil. Previously we have demonstrated in an acute colitis model a marked protective effect of a butanolic extract, so we decided to assess its anti-inflammatory effect in a chronic ulcerative colitis model induced by trinitrobenzensulfonic acid (TNBS). Abarema cochliacarpos (150 mg/day, v.o.) was administered for fourteen consecutive days. This treatment decreased significantly macroscopic damage as compared with TNBS. Histological analysis showed that the extract improved the microscopic structure. Myeloperoxidase activity (MPO) was significantly decreased. Study of cytokines showed that TNF-α was diminished and IL-10 level was increased after Abarema cochliacarpos treatment. In order to elucidate inflammatory mechanisms, expression of cyclooxygenase (COX)-2 and nitric oxide synthase (iNOS) were studied showing a significant downregulation. In addition, there was reduction in the JNK and p-38 activation. Finally, IκB degradation was blocked by Abarema cochliacarpos treatment being consistent with an up-regulation of the NF-kappaB-binding activity. These results reinforce the anti-inflammatory effects described previously suggesting that Abarema cochliacarpos could provide a source for the search for new anti-inflammatory compounds useful in ulcerative colitis treatment.

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Administration of ovalbumin by aerosol to sensitised rats produced a rapid (15 min) protein exudation in different airway tissues, as determined by Evans blue staining. This was associated with marked mast cell degranulation determined by histological examination, with there being no difference between mucosal and connective tissue mast cells. A 5-day administration regimen with compound 48/80 selectively depleted connective tissue mast cell (Positive to berberine staining) without modifying ovalbumin-induced plasma protein extravasation. Treatment of rats with dexamethasone (1 mg/kg, - 12 h) or nor-dihydroguaiaretic acid (30 mg/kg i.p., - 30 min) significantly reduced ovalbumin-induced protein extravasation and preserved mucosal mast cell morphology. Indomethacin (4 mg/kg i.v., - 30 min) exerted no effect on either parameter. In conclusion, we propose the mucosal mast cell as a target cell responsible at least partly for the inhibitory actions of known anti-inflammatory drugs. We suggest an involvement of endogenous leukotriene(s), but not prostanoid(s), in mucosal mast cell activation/degranulation. (C) 2001 Published by Elsevier B.V. B.V.

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Purpose: To compare a single intraoperative sub-Tenon's capsule triamcinolone acetonicle injection with steroid drops in the treatment of ocular inflammation after cataract surgery.Design: Randomized, double-masked controlled trial.Participants: A total of 100 patients were randomized prospectively into 2 groups: 50 patients treated with 1% prednisolone eyedrops (control group A) and 50 patients treated with sub-Tenon's capsule triamcinolone (treatment group B).Methods: All patients underwent phacoemulsification and intraocular posterior lens implantation. After surgery, patients were randomized to receive either (group B) an intraoperative 40 mg triamcinolone acetonicle sub-Tenon's capsule injection or (group A) 1% prednisolone acetate eyedrops, according to the following schedule: 1 drop 4 times daily (week 1), 3 times daily (week 2), 2 times daily (week 3), once daily (week 4). To mask the study, group B received vehicle drops administered on a similar schedule, and group A received an intraoperative sub-Tenon's capsule injection of a 1 ml balanced salt solution.Main Outcome Measures: the main outcome measures included inflammation (cell, flare, ciliary flush), intraocular pressure, and lack of response.Results: Triamcinolone was shown to have anti-inflammatory efficacy clinically equivalent to conventional 1% prednisolone eyedrops in reducing intraocular inflammation, as measured by clinical methods. Triamcinolone was found to be as safe as the prednisolone in terms of adverse effects, changes in visual acuity, intraocular pressure, and biomicroscopic and ophthalmoscopic variables. on the third, seventh, fourteenth, and twenty-eighth postoperative days, a significantly lower intraocular pressure (P<0.01) was noted in the triamcinolone group than in the prednisolone group.Conclusions: A single intraoperative 40-mg triamcinolone acetonide sub-Tenon's capsule injection demonstrated a clinically equivalent therapeutic response and ocular tolerance compared with 1% prednisolone drops in controlling postoperative inflammation after uncomplicated cataract surgery and merits further investigation. (C) 2004 by the American Academy of Ophthalmology.

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Objective and design: To investigate the effect of galectin-1 (Gal-1) and -3 (Gal-3) on leukocyte migration and analyze the expression of both galectins in inflammatory cells using a model of rat peritonitis.Material or Subjects: Sprague-Dawley rats (n = 4 per group).Treatment: Peritonitis was induced in animals through intraperitoneal injection of carrageenin (1.5 mg/kg) and rat mesenteries were analyzed at different time points (0, 4, 24 and 48h). For pharmacological treatment, rats received intravenous injection of Gal-1 or -3 (3 mu g/kg) followed by carrageenin.Methods: Western blotting and immunoelectron microscopy analysis. Statistical analysis was performed using ANOVA followed by Bonferroni test.Results: Pharmacological treatment with Gal-1, but not Gal-3, inhibited (similar to 50%) leukocyte recruitment into the peritoneal cavity at 4h time-point. In this early phase, immunogold staining of mesenteries showed a diminished Gal-3 expression in degranulated mast cells and Gal-1 in transmigrated neutrophils (similar to 20% reduction compared to intravascular cells). In the later phases (24 and 48 h), leukocyte turnover was associated with augmented Gal-1 expression in neutrophils and macrophages and Gal-3 in mast cells and macrophages.Conclusions: These results point to a balanced expression of cell-associated-Gal-1/Gal-3 and might impact on the development of new therapeutic strategies for inflammatory diseases.

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Background and Purpose Bone resorption induced by interleukin-1β (IL-1β) and tumour necrosis factor (TNF-α) is synergistically potentiated by kinins, partially due to enhanced kinin receptor expression. Inflammation-induced bone resorption can be impaired by IL-4 and IL-13. The aim was to investigate if expression of B1 and B2 kinin receptors can be affected by IL-4 and IL-13. Experimental Approach We examined effects in a human osteoblastic cell line (MG-63), primary human gingival fibroblasts and mouse bones by IL-4 and IL-13 on mRNA and protein expression of the B1 and B2 kinin receptors. We also examined the role of STAT6 by RNA interference and using Stat6-/- mice. Key Results IL-4 and IL-13 decreased the mRNA expression of B1 and B2 kinin receptors induced by either IL-1β or TNF-α in MG-63 cells, intact mouse calvarial bones or primary human gingival fibroblasts. The burst of intracellular calcium induced by either bradykinin (B2 agonist) or des-Arg10-Lys-bradykinin (B1 agonist) in gingival fibroblasts pretreated with IL-1β was impaired by IL-4. Similarly, the increased binding of B1 and B2 ligands induced by IL-1β was decreased by IL-4. In calvarial bones from Stat6-deficient mice, and in fibroblasts in which STAT6 was knocked down by siRNA, the effect of IL-4 was decreased. Conclusions and Implications These data show, for the first time, that IL-4 and IL-13 decrease kinin receptors in a STAT6-dependent mechanism, which can be one important mechanism by which these cytokines exert their anti-inflammatory effects and impair bone resorption. © 2013 The Authors. British Journal of Pharmacology © 2013 The British Pharmacological Society.

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OBJETIVO: Avaliar o efeito do resveratrol sobre a via de sinalização da insulina e melhora do quadro inflamatório no miocárdio de ratos Wistar obesos induzidos por dieta.MÉTODOS: Ratos Wistar foram divididos em grupos: controle (dieta padrão para roedores), obeso (dieta hiperlipídica) e obeso suplementado com resveratrol (20 mg/kg/dia), por 8 semanas (n=10). Ao final do período experimental, realizou-se o teste de tolerância à insulina, nos tempos 0 (sem insulina), 5, 10, 15, 20, 25 e 30 minutos após injeção intraperitoneal de insulina (2 U/kg). O peso corporal e o tecido adiposo epididimal foram mensurados. Fragmentos do miocárdio foram extraídos para análises da via da insulina e moléculas pró-inflamatórias através de Western blot.RESULTADOS: Os resultados indicam que a intervenção com resveratrol aumenta a constante de decaimento da glicose, fosforilação do receptor de insulina, substrato do receptor de insulina e da proteína quinase B. A suplementação de resveratrol também reduziu os níveis proteicos do fator de necrose tumoral alfa e de moléculas envolvidas com a transdução do sinal pró-inflamatório (quinase indutora do kappa B e fator nuclear kappa B). Os resultados ainda sugerem que a melhora na sensibilidade à insulina e a redução das moléculas pró-inflamatórias ocorreram independentemente da perda de peso corporal e da redução do tecido adiposo epididimal.CONCLUSÃO: A suplementação de resveratrol aumenta a sensibilidade à insulina, o que está relacionado à redução de fatores inflamatórios no miocárdio.

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Egg quality of semi-heavy laying hens fed on low protein diets (14.0% CP) and on different lysine levels is evaluated, while maintaining the same ratio of digestible amino acids / digestible lysine. Four hundred and twenty commercial strain Isa Brown laying hens, 28 weeks old, were divided into 42 experimental plots. A completely randomized design with six treatments and seven replicates was employed in four production cycles of 28 days each. Treatments comprised Control - 16.92% CP; 0.750% digestible lysine. Treatments 1 to 5, with CP levels 14% and digestible lysine levels 0.600, 0.675, 0.750, 0.825 and 0.900% respectively. Levels of Treatments 1 and 2 (0.546 and 0.640% digestible Met + Cys / 0.600 and 0.675% digestible lysine) provided smaller egg size. On the other hand, eggs had higher shell percentage when compared to control diet. When compared to other digestible amino acids, digestible lysine requirement may be estimated at 0.750% in a diet with 14% CP, which corresponds to the average daily intake of 876 mg dig. lysine hen-1 day-1 and 798 mg dig. Met + Cys hen-1 day-1, without jeopardizing performance and eggs' internal and external quality.

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The focus of this study was to evaluate the effect of lysine on the productive (weight and length gain, apparent feed conversion, specific growth rate and condition factor) and reproductive performance of Rhamdia voulezi males confined in net cages during the first reproductive cycle. The following parameters were assessed: seminal parameters (motility rate and duration, survival, sperm concentration, morphology, pH and osmolarity), hormonal parameters (cortisol and testosterone), testicular tissue (histomorphology), organosomatic indices (gonadosomatic, hepatosomatic and viscerosomatic indices) and composition of essential amino acids, crude protein and moisture of whole carcass. Four hundred fish were used, distributed in a random experimental design with four treatments and four replications in 16 net cages with 25 fish each. The treatments consisted of four different diets prepared so as to contain the following levels of lysine: 1.20, 1.40, 1.60 and 1.80%, with 30% crude protein and 3500 kcal kg(-1) digestible energy for 185 days (Jul./12-Jan./13). Eighteen males were selected per treatment, and they all released semen after slight abdominal pressure. The males were weighed, measured, submitted to hypophysation (2.5 mg kg(-1) carp pituitary extract), and then had their semen and blood collected. The fish were sacrificed by cervical dislocation, dissected, and the testes, liver, fat and guts were removed and weighed. The effects (p < 0.05) for the means of final weight, weight gain, apparent feed conversion and condition factor were observed for the analysis of productive performance. With regard to the reproductive parameters, only the seminal volume was affected (p < 0.05). Thus, the levels of testosterone showed quadratic effect (p < 0.05). The anatomy and the histomorphology of the testes were similar between the treatments during the spermiation period. With regard to the organosomatic indices, there was no influence (p > 0.05) between the treatments. The amino acids in the carcass were not affected (p > 0.05). The increment of lysine in the diet provided linear increase for weight gain and seminal volume and linear decrease for feed conversion in R. voulezi broodstocks confined in net cages. (C) 2014 Elsevier B.V. All rights reserved.

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The aim of this study was to determine the coefficients of the Goettingen model for Redbro birds and estimate the digestible lysine requirements. To determine the model parameters, three nitrogen balance trials were performed in Periods I (14-28 days), II (42-56 days) and III (70-84 days), using 42 birds per trial. The birds were individually housed and subjected to six diets with increasing levels of nitrogen, with lysine as the limiting amino acid (deficient by 20% in relation to other amino acids). Dietary nitrogen concentrations were 8, 16, 24, 32, 40 and 48 g/kg. A control diet was added to confirm lysine as the first limiting amino acid. Nitrogen balance trials were divided into 5 days of adaptation and two periods of excreta collection, each one of 5 days. The response of the birds to a control diet confirmed that lysine was the first limiting amino acid. The adjustment of the exponential functions between nitrogen retention or excretion and nitrogen intake allowed estimation of parameters of the Goettingen model. The maximum potential for nitrogen retention was 3276, 2585 and 2603 mg/BWkg0.67.day, nitrogen maintenance requirement was 225, 135 and 122 mg/BWkg0.67.day and efficiency of nitrogen utilisation was 313 x 10(-6), 406 x 10(-6) and 415 x 10(-6) in the phases of 14-28, 42-56 and 70-84 days. The digestible lysine intake for Periods I, II and III, based on 60% of the maximum potential for nitrogen retention, was 711, 989 and 1272 mg/day (1.225%, 1.137% and 1.09% of lysine in the diet for a daily feed intake of 58, 87 and 117 g/day), respectively.