997 resultados para Drugs- pre-formulation


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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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OBJETIVO: Comparar através de infusão contínua de xilazina ou medetomidina associada à metotrimeprazina e buprenorfina, cetamina e midazolam, o grau de hipnose, miorrelaxamento e qualidade anestésica e a viabilidade cirúrgica, avaliando eventuais alterações paramétricas e qualidade de recuperação. MÉTODOS: Foram utilizados 20 cães fêmeas, adultas, hígidas (3 a 5 anos de idade) com peso corporal entre 7 e 15 quilos, escolhidas e distribuídas aleatoriamente de forma homogênea em 2 grupos de 10 animais cada, (n=10) sendo estes designados por Grupo 1 (G1), e Grupo 2 (G 2). em G1, os animais foram submetidos a um pré-tratamento com metotrimeprazina na dose de 1,0 mg/kg e buprenorfina na dose de 0,003mg/kg ou 3 µg/kg intravenoso. Decorridos 15 minutos, administrou-se cetamina na dose de 5,0 mg/kg e midazolam na dose de 0,2 mg/kg intravenoso. Imediatamente após a indução iniciou-se administração contínua, por um período de 30 minutos, da associação anestésica de midazolam 0,4 mg/kg/h, cetamina 20mg/kg/h e xilazina 1,0 mg/kg/h IV. em G 2 utilizou-se a mesma técnica empregada em G1 substituindo-se, a xilazina pela medetomidina na dose de 30µg/kg/h. RESULTADOS: Verificou-se em G1 bloqueio átrio-ventricular de primeiro e segundo grau, período de recuperação mais longo além de menor qualidade. em G 2 observou-se bloqueio átrio-ventricular de primeiro grau isolado e de ação fugaz. CONCLUSÕES: Ao se aplicar o método de infusão contínua, além da redução dos fármacos aplicados, evitaram-se efeitos colaterais permitindo uma recuperação mais tranqüila e isenta de excitações, ambos os protocolos permitiram a realização do ato cirúrgico (ovário-salpingo-histerectomia), causando uma redução da hipnose e um miorrelaxamento acentuado. A xilazina e a medetomidina apresentam um comportamento farmacodinâmico semelhante, porém com aspectos clínicos diferentes, as alterações eletrocardiográficas observadas em G 2 e em menor grau em G1 devem ser melhor estudadas.

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A rapid and simple method for procaine determination was developed by flow injection analysis (FIA) using a screen-printed carbon electrode (SPCE) as amperometric detector. The present method is based on the amine/hydroxylamine oxidation from procaine monitored at 0.80 V on SPCE in sodium acetate solution pH 6.0. Using the best experimental conditions assigned as: pH 6.0, flow rate of 3.8 mL min(-1), sample volume of 100 mu L and analytical path of 30 cm it is possible to construct a linear calibration curve from 9.0 x 10(-6) to 1.0 x 10(-4) mol L-1. The relative standard deviation for 5.0 x 10(-5) mol L-1 procaine (15 repetitions using the same electrode) is 3.2% and detection limit calculated is 6.0 x 10(-6) mol L-1. Recoveries obtained for procaine gave a mean values from 94.8 to 102.3% and an analytical frequency of 36 injections per hour was achieved. The method was successfully applied for the determination of procaine in pharmaceutical formulation without any pre-treatment, which are in good accordance with the declared values of manufacturer and an official method based on spectrophotometric analysis. (c) 2006 Elsevier B.V. All rights reserved.

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This article deals with some methodologies for economic and technical evaluations of cogeneration projects proposed by several authors. A discussion on design philosophy applied to thermal power plants leads to the decision problem of a conflicting, multiobjective formulation that includes the most important parameters. This model is formulated to help decision makers and designers in choosing compromise values for included parameters. (C) 1997 Elsevier B.V. Ltd.

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The acquisition and update of Geographic Information System (GIS) data are typically carried out using aerial or satellite imagery. Since new roads are usually linked to georeferenced pre-existing road network, the extraction of pre-existing road segments may provide good hypotheses for the updating process. This paper addresses the problem of extracting georeferenced roads from images and formulating hypotheses for the presence of new road segments. Our approach proceeds in three steps. First, salient points are identified and measured along roads from a map or GIS database by an operator or an automatic tool. These salient points are then projected onto the image-space and errors inherent in this process are calculated. In the second step, the georeferenced roads are extracted from the image using a dynamic programming (DP) algorithm. The projected salient points and corresponding error estimates are used as input for this extraction process. Finally, the road center axes extracted in the previous step are analyzed to identify potential new segments attached to the extracted, pre-existing one. This analysis is performed using a combination of edge-based and correlation-based algorithms. In this paper we present our approach and early implementation results.

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Background: Blood pressure (BP) within pre-hypertensive levels confers higher cardiovascular risk and is an intermediate stage for full hypertension, which develops in an annual rate of 7 out of 100 individuals with 40 to 50 years of age. Non-drug interventions to prevent hypertension have had low effectiveness. In individuals with previous cardiovascular disease or diabetes, the use of BP-lowering agents reduces the incidence of major cardiovascular events. In the absence of higher baseline risk, the use of BP agents reduces the incidence of hypertension. The PREVER-prevention trial aims to investigate the efficacy, safety and feasibility of a population-based intervention to prevent the incidence of hypertension and the development of target-organ damage.Methods: This is a randomized, double-blind, placebo-controlled clinical trial, with participants aged 30 to 70 years, with pre-hypertension. The trial arms will be chlorthalidone 12.5 mg plus amiloride 2.5 mg or identical placebo. The primary outcomes will be the incidence of hypertension, adverse events and development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG. The secondary outcomes will be fatal or non-fatal cardiovascular events: myocardial infarction, stroke, heart failure, evidence of new sub-clinical atherosclerosis, and sudden death. The study will last 18 months. The sample size was calculated on the basis of an incidence of hypertension of 14% in the control group, a size effect of 40%, power of 85% and P alpha of 5%, resulting in 625 participants per group. The project was approved by the Ethics committee of each participating institution.Discussion: The early use of blood pressure-lowering drugs, particularly diuretics, which act on the main mechanism of blood pressure rising with age, may prevent cardiovascular events and the incidence of hypertension in individuals with hypertension. If this intervention shows to be effective and safe in a population-based perspective, it could be the basis for an innovative public health program to prevent hypertension in Brazil.Trial Registration: Clinical Trials NCT00970931. © 2011 Fuchs et al; licensee BioMed Central Ltd.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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Introduction Visceral leishmaniasis (VL) is caused by the intracellular protozoan Leishmania donovani complex. VL may be asymptomatic or progressive and is characterized by fever, anemia, weight loss and the enlargement of the spleen and liver. The nutritional status of the patients with VL is a major determinant of the progression, severity and mortality of the disease, as it affects the clinical progression of the disease. Changes in lipoproteins and plasma proteins may have major impacts in the host during infection. Thus, our goal was evaluate the serum total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides, glucose, albumin, globulin and total protein levels, as well as the body composition, of VL patients before and after treatment. Methods Nutritional evaluation was performed using the bioelectrical impedance analysis (BIA) to assess body composition. Biochemical data on the serum total cholesterol, HDL, LDL, triglycerides, glucose, albumin, globulin and total protein were collected from the medical charts of the patients. Results BIA indicated that both pre-treatment and post-treatment patients exhibited decreased phase angles compared to the controls, which is indicative of disease. Prior to treatment, the patients exhibited lower levels of total body water compared to the controls. Regarding the biochemical evaluation, patients with active VL exhibited lower levels of total cholesterol, HDL, LDL and albumin and higher triglyceride levels compared to patients after treatment and the controls. Treatment increased the levels of albumin and lipoproteins and decreased the triglyceride levels. Conclusions Our results suggest that patients with active VL present biochemical and nutritional changes that are reversed by treatment.

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Making bioproducts available to the market requires finding appropriate processes for mass production and formulation of biological agents. This study aimed at evaluating the Bipolaris euphorbiae production in a solid medium (fermentation in solid substrate) and in a biphasic system (growth in a liquid medium followed by growth in a solid medium), as well as determining the processes for collecting and drying conidia, under laboratory conditions. The influence of the incubation period and inoculum quantity were also investigated. The conidia were dried by using an oven (30ºC, 35ºC, 40ºC, 45ºC, 50ºC, 55ºC and 60ºC), and laminar flow, continuous air flow and aseptic chamber at room temperature. Dry conidia were obtained by sieving and grinding in a ball mill, hammer mill or grain grinder. The conidia viability and sporulation efficiency were evaluated in the solid medium and in the biphasic system. For growth period, the best sporulation on solid medium was obtained after 10 days of incubation, reaching 8.3 x 10(7) conidia g-1 of substrate. The biphasic system did not increase the B. euphorbiae sporulation (4.5 x 10(7) conidia g-1 of substrate), after 14 days, and the amount of liquid inoculum used in this system was not an important factor for increasing its production. The continuous air flow and laminar flow preserved the conidial viability (94.6% and 99.1%, respectively), while promoting a great moisture loss (62.6% and 54.0%, respectively). All the grinding processes reduced the conidia germination (86.2%, 10.5% and 12%, respectively), while sieving allowed the collecting of powdered conidia with high viability (94.8%).

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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Cisplatin is an effective antineoplastic drug. However, it provokes considerable collateral effects, including genotoxic and clastogenic activity. It has been reported that a diet rich in glutamine can help inhibit such collateral effects. We evaluated this activity in 40 Swiss mice, distributed into eight experimental groups: G1 - Control group (PBS 0.1 mL/10g body weight); G2 - cisplatin group (cisplatin 6 mg/kg intraperitoneally); G3, G4, G5 - glutamine groups (glutamine at 150, 300, and 600 mg/kg, respectively; orally); G6, G7, G8 - Pre-treatment groups (glutamine at 150, 300, and 600 mg/kg, respectively; orally and cisplatin 6 mg/kg intraperitonially). For the micronucleus assay, samples of blood were collected (before the first use of the drugs at T0, then 24 (T1) and 48 (T2) hours after the first administration). For the comet assay, blood samples were collected only at T2. The damage reduction percentages for the micronucleus assay were 90.0, 47.3, and 37.3% at T1 and 46.0, 38.6, and 34.7% at T2, for G6, G7, and G8 groups, respectively. For the comet assay, the damage reduction percentages were 113.0, 117.4, and 115.0% for G6, G7, and G8, respectively. We conclude that glutamine is able to prevent genotoxic and clastogenic damages caused by cisplatin.

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Ethnopharmacological relevance: In Brazil, a phytotherapeutic preparation produced from a standardized tincture of Cinchona calisaya Weddel such that each mL of product contains 400 mu g of quinine, known in Portuguese as Agua Inglesa (R) (English water), is indicated by the manufacturer as a tonic, appetite stimulant, and digestive. However, this preparation has long been used in folk medicine as a female fertility stimulant. Despite its widespread use in folk medicine to stimulate female fertility, no study has been undertaken to assess the potential teratogenic and genotoxic effects of this phytotherapeutic preparation. The aim of the present study was to investigate possible toxic reproductive effects in mice caused by exposure to Agua Inglesa (R), either before mating or during the pre- and post-embryo implantation periods. The genotoxic potential was evaluated using the micronucleus assay.Material, Methods, and Results: Virgin female mice, with at least one estrous cycle evidenced by vaginal cytology, were divided into five groups of 15 individuals each (Group I - control, Group II - treated with ethanol solution at 16%, Groups III, IV and V treated with phytotherapeutic preparation at 1.5 mL/kg/day, 3.0 mL/kg/day and 4.5 mL/kg/day, respectively). After the first 28 days of treatment, females were caged individually with adult fertile males. Pregnant females continued to receive treatment for seven days (preimplantation period). Body weight was recorded weekly during treatment. Signs of toxicity (weight loss, food intake, piloerection, apathy, prostration, diarrhea, seizures, behavioral changes, and locomotion) were also observed. The females were sacrificed on the 15th day of pregnancy, uterine horns were evaluated for implantation, and the placental index was recorded. In the micronucleus test, 2000 polychromatic erythrocytes (PCE) per animal, obtained from bone marrow, were scored. Results The results showed that exposure of the females during the pre- and post-implantation periods did not significantly alter the reproductive capacity (p < 0.05); however, in higher dose (three times human dose)reduction of fetal weight was observed. There was no difference between the control and phytotherapeutic preparation (p > 0.05) in terms of the average number of micronucleated polychromatic erythrocytes.Conclusions: Although folk medicine suggests that the Agua Inglesa (R) preparation is useful as a female fertility stimulant, no such effect was confirmed in mice. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)