139 resultados para Concomitant Methotrexate
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Introduction: The aim of this study is to evaluate the serum activity of metalloproteinases (MMPs) -2 and -9 as predictors of pressure ulcer (PU), gait status and mortality 6 months after hip fracture. Methods: Eighty-seven patients over the age of 65 admitted to the orthopedic unit from January to December 2010 with hip fracture were prospectively evaluated. Upon admission, patient demographic information, including age, gender and concomitant diseases, was recorded. Blood samples were taken for analysis of MMP -2 and -9 activity by gel zymography and for biochemical examination within the first 72 hours of the patient's admission, after clinical stabilization. The fracture pattern (neck, trochanteric or subtrochanteric), time from admission to surgery, surgery duration and length of hospital stay were also recorded. Results: Two patients were excluded due to the presence of pathological fractures (related to cancer), and three patients were excluded due to the presence of PU before admission. Eighty-two patients, with a mean age of 80.4 ± 7.3 years, were included in the analysis. Among these patients, 75.6% were female, 59.8% had PU, and 13.4% died 6 months after hip fracture. All patients underwent hip fracture repair. In a univariate analysis, there were no differences in serum MMP activity between hip fracture patients with or without PU. In addition, the multiple logistic regression analysis models, which were adjusted by age, gender, length of hospital stay and C-reactive protein, showed that the pro-MMP-9 complexed with neutrophil gelatinase-associated lipocalin form (130 kDa) was associated with gait status recovery 6 months after hip fracture. Conclusions: In conclusion, serum pro-MMP-9 is a predictor of gait status recovery 6 months after hip fracture. © 2013 Gumieiro et al.
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The purpose of this study was to determine whether the aerobic training-induced fiber-type transition in different muscles is associated with alterations in NFAT isoforms gene expression. We hypothesized that the aerobic training-induced fiber-type transition would be mediated by NFATc1-c3 isoforms without altering the CaN expression. Male Wistar rats (80 days old) were divided into a trained group (T; n=8) that underwent an 8-wk swimming endurance training program (5 days/week) and a control group (C; n=8). After the experimental period, the animals were sacrificed, and the soleus (SOL) and plantaris (PL) muscles were collected for morphometrical, histochemical and molecular analyses. Aerobic training induced a type I-to-type IIA fiber transition in the SOL muscle and a type IIB-to-type IIA fiber transition in the PL muscle, which were concomitant with a significant (p<0.05) increase in NFATc1-c3 gene expression in both the SOL and PL muscles. In contrast, the expression levels of calcineurin (CaN) and NFATc4 remained unchanged. Therefore, our results showed that fiber type switching induced by aerobic training is mediated by NFATc1-c3 isoforms without altering the CaN expression. © Georg Thieme Verlag KG Stuttgart. New York.
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Given that cancer is one of the main causes of death worldwide, many efforts have been directed toward discovering new treatments and approaches to cure or control this group of diseases. Chemotherapy is the main treatment for cancer; however, a conventional schedule based on maximum tolerated dose (MTD) shows several side effects and frequently allows the development of drug resistance. On the other side, low dose chemotherapy involves antiangiogenic and immunomodulatory processes that help host to fight against tumor cells, with lower grade of side effects. In this review, we present evidence that metronomic chemotherapy, based on the frequent administration of low or intermediate doses of chemotherapeutics, can be better than or as efficient as MTD. Finally, we present some data indicating that noncytotoxic concentrations of antineoplastic agents are able to both up-regulate the immune system and increase the susceptibility of tumor cells to cytotoxic T lymphocytes. Taken together, data from the literature provides us with sufficient evidence that low concentrations of selected chemotherapeutic agents, rather than conventional high doses, should be evaluated in combination with immunotherapy. Copyright © 2012 UICC.
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Despite the improvements in neoadjuvant chemotherapy, the outcome of patients with advanced bladder cancer has changed very little over the past 30 years. In the present study we tested and compared the in vitro antitumor activities of four different inhibitors of Polo-like kinase 1 (PLK1) (BI 2536, BI 6727, GW843682X, and GSK461364), against 3 bladder carcinoma cell lines RT4, 5637 and T24. The impact on radiosensitivity and drug interactions in simultaneous treatments with cisplatin, methotrexate, and doxorubicin were also investigated. Our results showed that PLK1 inhibition prevented cell proliferation and clonogenicity, causing significant inhibition of invasion of tumor cells, though modest differences were observed between drugs. Moreover, all PLK1 inhibitors induced G2/M arrest, with the subsequent induction of death in all 3 cell lines. Drug interactions studies showed auspicious results for all PLK1 inhibitors when combined with the commonly used cisplatin and methotrexate, though combinations with doxorubicin showed mostly antagonistic effects. Comparably, the four PLK1 inhibitors efficiently sensitized cells to ionizing radiation. Our findings demonstrate that irrespective of the inhibitor used, the pharmacological inhibition of PLK1 constrains bladder cancer growth and dissemination, providing new opportunities for future therapeutic intervention. However, further laboratorial and preclinical tests are still needed to corroborate the usefulness of using them in combination with other commonly used chemotherapeutic drugs. © 2013 Landes Bioscience.
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Sporotrichosis is a subcutaneous mycosis that is caused by the dimorphic fungus Sporothrix schenckii. This disease generally occurs within the skin and subcutaneous tissues, causing lesions that can spread through adjacent lymphatic vessels and sometimes leading to systemic diseases in immunocompromised patients. Macrophages are crucial for proper immune responses against a variety of pathogens. Furthermore, macrophages can play different roles in response to different microorganisms and forms of activation, and they can be divided into classic or alternatively activated populations, as also known as M1 and M2 macrophages. M1 cells can lead to tissue injury and contribute to pathogenesis, whereas M2 cells promote angiogenesis, tissue remodeling, and repair. The aim of this study was to investigate the roles of M1 and M2 macrophages in a sporotrichosis model. Toward this end, we performed phenotyping of peritoneal exudate cells and evaluated the concomitant production of several immunomediators, including IL-12, IL-10, TGF-β, nitric oxide, and arginase-I activity, which were stimulated ex vivo with cell wall peptide-polysaccharide. Our results showed the predominance of the M2 macrophage population, indicated by peaks of arginase-I activity as well as IL-10 and TGF-β production during the 6th and 8th weeks after infection. These results were consistent with cellular phenotyping that revealed increases in CD206-positive cells over this period. This is the first report of the participation of M2 macrophages in sporotrichosis infections. © 2013 Springer Science+Business Media Dordrecht.
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Estimating equations of global radiation based on the sunshine duration were proposed for horizontal surface and with inclination of 12.85, 22.85 and 32.85° facing the North in Botucatu, SP, Brazil, in monthly, seasonal and annual groupings of data. Simple linear correlations were applied (for definition of the linear and angular coefficients of Angstrom-Prescott model), in a database measured in all three inclinations in different periods (22.85°: 04/1998 to 07/2001; 12.85°: 08/2011 to 02/2003; and 32.85°: 03/2003 to 12/2007) concomitant with horizontal measures and sunshine duration. The statistical performance of the model was analysed by the means absolute error (MBE), the square root of the mean square error (RMSE) and the index adjustment (d). The minimum global radiation transmissivity varied from 14.35% in August (12.85°) to 27.86% in December (32.85°) and the maximum transmissivity ranged between 62.10% and 78.90%, for June (32.85°) and December (12.85°). Increasing the angle of inclination surface increased the scattering and decreased the index of adjustment and performance. The worst results were found for application of the seasonal and annual models in the months of autumn and winter for 32.85° (RMSE below 42.93% and adjustment superior to 0.4693).
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Statistical equations were obtained and evaluated with annual, seasonal and monthly data groupings for estimates of direct and diffuse components of solar radiation based on the sunshine duration (ratio of sunshine and photoperiod) incident on horizontal and inclined surfaces to 12.85, 22.85 and 32.85° with facing to North, in Botucatu, SP. The ratios between the two components and radiation at the top of the atmosphere were used, in a database whose inclinations were measured in three different periods (22.85°: 04/1998 to 07/2001; 12.85°: 08/2011 to 02/2003; and 32.85°: 03/2003 to 12/2007) and concomitant with horizontal measures and sunshine duration. The correlations showed a linear and second degree polynomial behavior for the direct and diffuse radiation, with higher coefficients of determination in periods of low variation in the coverage of the sky (cloudiness). The highest values of the direct and diffuse radiation were found in winter and summer, respectively for all surfaces evaluated. The increase in the inclination angle decreased the performance of equations in all groups of data with increase in scattering and decrease in index of the adjustment, however, the monthly equations allowed better performance for the two components.
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Pós-graduação em Artes - IA
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Pós-graduação em Biologia Geral e Aplicada - IBB
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
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Pós-graduação em Pesquisa e Desenvolvimento (Biotecnologia Médica) - FMB
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Pós-graduação em Medicina Veterinária - FCAV