999 resultados para Dose-réponse


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The acute administration of an indirect activator of the enzyme pyruvate dehydroge-nase (PDH) in human athletes causes a reduction in blood lactate level during and after exercise. A single IV dose (2.5m.kg-1) of dichloroacetate (DCA) was administered before a submaximal incremental exercise test (IET) with five velocity steps, from 5.0 m.s-1 for 1 min to 6.0, 6.5, 7.0 and 7.5m.s-1 every 30s in four untrained mares. The blood collections were done in the period after exercise, at times 1, 3, 5, 10, 15 and 20 min. Blood lactate and glucose (mM) were determined electro-enzymatically utilizing a YSI 2300 automated analyzer. There was a 15.3% decrease in mean total blood lactate determined from the values obtained at all assessment times in both trials after the exercise. There was a decrease in blood lactate 1, 3, 5, 10, 15 and 20 min after exercise for the mares that received prior DCA treatment, with respective mean values of 6.31±0.90 vs 5.81±0.50, 6.45±1.19 vs 5.58±1.06, 6.07±1.56 vs 5.26±1.12, 4.88±1.61 vs 3.95±1.00, 3.66±1.41 vs 2.86±0.75 and 2.75±0.51 vs 2.04±0.30. There was no difference in glucose concentrations. By means of linear regression analysis, V140, V160, V180 and V200 were determined (velocity at which the rate heart is 140, 160, 180, and 200 beats/minute, respectively). The velocities related to heart rate did not differ, indicating that there was no ergogenic effect, but prior administration of a relatively low dose of DCA in mares reduced lactatemia after an IET.

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This study was designed to determine the genotoxicity of a supraphysiological dose of triiodothyronine (T3) in both obese and calorie-restricted obese animals. Fifty male Wistar rats were randomly assigned to one of the two following groups: control (C; n = 10) and obese (OB; n = 40). The C group received standard food, whereas the OB group was fed a hypercaloric diet for 20 weeks. After this period, half of the OB animals (n = 20) were subjected to a 25%-calorie restriction of standard diet for 8 weeks forming thus a new group (OR), whereas the remaining OB animals were kept on the initial hypercaloric diet. During the following two weeks, 10 OR animals continued on the calorie restriction diet, whereas the remaining 10 rats of this group formed a new group (ORS) given a supraphysiological dose of T3 (25 μg/100 g body weight) along with the calorie restriction diet. Similarly, the remaining OB animals were divided into two groups, one that continued on the hypercaloric diet (OB, n = 10), and one that received the supraphysiological dose of T3 (25 μg/100 g body weight) along with the hypercaloric diet (OS, n = 10) for two weeks. The OB group showed weight gain, increased adiposity, insulin resistance, increased leptin levels and genotoxicity; T3 administration in OS animals led to an increase in genotoxicity and oxidative stress when compared with the OB group. The OR group showed weight loss and normalized levels of adiposity, insulin resistance, serum leptin and genotoxicity, thus having features similar to those of the C group. On the other hand, the ORS group, compared to OR animals, showed higher genotoxicity. Our results indicate that regardless of diet, a supraphysiological dose of T3 causes genotoxicity and potentiates oxidative stress. © 2013 de Sibio et al.

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Fipronil is a neurotoxic insecticide that inhibits the gamma-aminobutyric acid receptor and can affect gustative perception, olfactory learning, and motor activity of the honeybee Apis mellifera. This study determined the lethal dose (LD50) and the lethal concentration (LC50) for Africanized honeybee and evaluated the toxicity of a sublethal dose of fipronil on neuron metabolic activity by way of histochemical analysis using cytochrome oxidase detection in brains from worker bees of different ages. In addition, the present study investigated the recovery mechanism by discontinuing the oral exposure to fipronil. The results showed that mushroom bodies of aged Africanized honeybees are affected by fipronil, which causes changes in metabolism by increasing the respiratory activity of mitochondria. In antennal lobes, the sublethal dose of fipronil did not cause an increase in metabolic activity. The recovery experiments showed that discontinued exposure to a diet contaminated with fipronil did not lead to recovery of neural activity. Our results show that even at very low concentrations, fipronil is harmful to honeybees and can induce several types of injuries to honeybee physiology. © 2012 Springer Science+Business Media New York.

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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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In this work, the effect of gamma radiation on the optical properties of polymetallayne poly[1,1'-bis(ethynyl)-4,4'-biphenyl(bis-tributylphosphine)Pt(II) ] (Pt-DEBP) in chloroform solution is studied. The samples were irradiated at room temperature with doses from 0.01 Gy to 1 Gy using a 60Co gamma ray source. A new band at 420 nm is observed in the emission spectra, in superposition to the emission maximum at 398 nm, linearly dependent on dose. We propose to use the ratio of the emission amplitude bands as the dosimetric parameter. This method proved to be robust, accurate, and can be used as a dosimeter in medical applications. © 2013 AIP Publishing LLC.

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Diuron [3-(3,4-dichlorophenyl)-1,1-dimethylurea] is a herbicide that induced urothelial tumors in the urinary bladder of Wistar rats fed 2500. ppm during a long-term study. The currently suggested non-genotoxic mode of action (MOA) of diuron encompasses in succession urothelial necrosis induced by direct cytotoxicity, regenerative cell proliferation and sustained urothelial hyperplasia that increases the likelihood of neoplasia development. This study evaluated the dose-response profile of urothelial histological and ultrastructural lesions induced by diuron. Sixty male Wistar rats were fed ad libitum diuron mixed in the diet at 0, 60, 125, 500, 1250, or 2500. ppm for 20 weeks. The incidences of urothelial simple hyperplasia and the cell proliferation index were significantly increased in the diuron-fed 1250 and 2500. ppm groups. By scanning electron microscopy, the incidences and severity of lesions were significantly increased in the 500 and 1250. ppm groups. The incidences of urothelial hyperplasia in the kidney pelvis were significantly increased in the 500, 1250 and 2500. ppm groups. The present study documents the dose-response influence of diuron on the rat urothelium, with a no observed effect level (NOEL) at 125. ppm; 1250. ppm was as effective as 2500. ppm at inducing urothelial lesions. © 2013 Elsevier B.V.

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Pós-graduação em Pesquisa e Desenvolvimento (Biotecnologia Médica) - FMB

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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Pós-graduação em Agronomia (Energia na Agricultura) - FCA

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Pós-graduação em Ciências da Motricidade - IBRC

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)