641 resultados para fármaco
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Estudaram-se os efeitos do carprofeno, aplicado por diferentes vias, em uveítes experimentais em cães. Realizou-se paracentese de câmara anterior em dois momentos (M0 e M1), com intervalo de cinco horas entre si. em M0 e M1, colheram-se 0,2mL de humor aquoso e determinaram-se as concentrações de proteína total e de prostaglandina E2 (PGE2). Constituíram-se quatro grupos (n = 8), que receberam carprofeno ao final de M0 pelas vias subcutânea (GI), subconjuntival (GII) e tópica (GIII). Um quarto grupo não recebeu tratamento (controle). Procedeu-se à avaliação histopatológica nos indivíduos do GII. em todos os grupos, encontrou-se aumento significativo dos níveis proteicos e de PGE2 em M1. Não se observou diferença significativa, em M1, entre os grupos para nenhum dos parâmetros estudados. Exsudado inflamatório de caráter agudo e hemorragia discreta foram vistos à histopatologia após a aplicação do fármaco. O carprofeno foi ineficaz em inibir a síntese de PGE2 e o influxo de proteínas para a câmara anterior, por qualquer uma das vias testadas. Contudo, a redução de 44% nos níveis de proteínas (via tópica), sugere que por esta via ele pode ser utilizado como adjuvante no controle da uveíte em cães.
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Currently, studies in the area of polymeric microcapsules and nanocapsules and controlled release are considerably advanced. This work aims the study and development of microcapsules and nanocapsules from Chitosan/MDI, using a new technique of interfacial polycondensation combined to spontaneous emulsification, for encapsulation of BZ-3. It was firstly elaborated an experimental design of 23 of the particle in white without the presence of BZ-3 and Miglyol, where the variables were the concentrations of MDI, chitosan and solvent. Starting from the data supplied by the experimental design was chosen the experiment with smaller particle diameter and only added like this BZ-3 and Miglyol. The suspension containing concentrations of 6.25 mg/mL, 12.5 mg/mL, 18.75 mg/mL, 25 mg/mL of BZ-3 were prepared, nevertheless, during the storage time, these formulations presented drug precipitates in the suspensions of 18.75 mg/mL and 25 mg/mL of BZ-3. This apparition of precipitate was attributed to the diffusion of BZ-3 for the aqueous phase without any encapsulation, suggesting so the use of the smaller concentrations of the BZ-3. The suspension containing 6.25mg/mL of BZ3 presented average size of 1.47μm, zeta potential of 61 mV, pH 5.64 and this sample showed an amount of BZ-3 and drug entrapment of 100 %. The suspension containing 12.5mg/mL of BZ-3 presented average size of 1.76μm, zeta potential of 47.4 mV, pH 5.71 and this sample showed an amount of BZ-3 and drug entrapment of 100 %. Then, showing such important characteristics, these two formulations were chosen for futher continuity to the study. These formulations were also characterized by the morphology, FTIR, stability for Turbiscan, DSC and a study of controlled release of the BZ-3 was elaborated in different receiving means
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One of the main impacts to the environment is the water pollution, where the industrial sector is one of the main sources of this problem. In order to search for a solution, the industrial sector is looking forward to new technologies to treat its wastewaters with the goal to reuse the water in the own process. In this mode, the treatment presents a reduction in its costs with the water suply. One of these technologies that are getting more and more applications is the advanced oxidative processes (AOP´s). In this work two industrial wastewaters have been studied, i.e., containing polymers and pharmacus. In the case of the wastewaters with polymers the UV/H2O2 process has been applied with a systematic series of experiments, using irradiation from a mercury lamp and also solar. The following variables of the UV/H2O2 process for the polymers wastewaters have been studied systematically with the lamp reactor: mode of addition of hydrogen peroxide, temperature, time of reaction, hydrogen peroxide concentration and power of the lamp (80, 125, 250 and 400W). The results demonstrated to be satisfactory, obtaining rates of organic charge removal of 100% in 120 minutes of reaction. The studied variables for the experiments with solar irradiation using polymers wastewaters were only the time of reaction, the mode of addition and concentration of the hydrogen peroxide. The results with the solar irradiation demonstrated to be not satisfactory, reaching maximum of 22% of TOC removal in 240 minutes of reaction. This is in accordance with the fact that the solar source has only 5% of low UV irradiation. With respect to the photodegradation of the pharmacus wastewaters, the process UV/H2O2 and photo-Fenton have been applied. As a source of photons, in this case, a mercury UV lamp of 80 W has been used. The studied variables for the experiments with artificial irradiation with the pharmacus wastewaters were: initial concentration of the pollutant, concentration of Fe2+ and time of reaction. The results demonstrated a degree of degradation fairly satisfactory, showing a maximum conversion value of 46% in 120 minutes
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Um hidrogel foi desenvolvido a partir de dextrano 70 kDa (DEX-70) e praziquantel incorporado (PZQ) como fármaco modelo. Propriedades biofarmacêuticas, como solubilidade e velocidade de dissolução, foram analisadas no desenvolvimento do hidrogel. Além disso, o hidrogel também foi caracterizado por espectroscopia na região do infravermelho e calorimetria diferencial exploratória (DSC). Testes da taxa de intumescimento mostraram que o hidrogel intumesce lentamente, embora tenha sido mais rápido do que a taxa do polímero livre. Nos testes de dissolução, o hidrogel liberou o fármaco lenta e continuamente. Esta liberação lenta foi semelhante a observada nos testes de intumescimento e resultou em uma liberação controlada do fármaco. Assim, o dextrano 70 kDa é um polímero adequado para o desenvolvimento de hidrogéis como veículos para a liberação controlada de fármacos.
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
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A mistura de tensoativos com água, em determinadas proporções, na ausência ou na presença de substâncias lipofílicas pode formar diferentes tipos de agregados, entre os quais agregados polimorfos representados pelas microemulsões (ME) e mesofases liotrópicas - os cristais líquidos (LC), que estão intimamente ligados com a proporção e a natureza dos componentes da mistura. Nesse trabalho, foi discutido o papel desses sistemas na incorporação de fármacos com diferentes propriedades físico-químicas, influenciando fortemente a liberação, assim como a biodisponibilidade dos fármacos. Aspectos sobre a formação e a caracterização de microemulsões e cristais líquidos também foram discutidos. A análise da literatura indicou que, dependendo da polaridade do fármaco, o efeito da ME ou LC pode ser usado para otimizar o efeito terapêutico por meio do controle da velocidade ou do mecanismo de liberação do fármaco.
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
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Este trabalho avaliou a influência da concentração de amido de milho nas características físicas e na liberação in vitro de paracetamol a partir de comprimidos. Os granulados foram analisados quanto à granulometria e densidades aparentes bruta e compactada e os comprimidos quanto ao peso médio, espessura, dureza, friabilidade, tempo de desintegração. Os comprimidos foram preparados a partir de granulados obtidos por granulação a úmido, utilizando cozimento de amido a 10% como agente granulante, segundo três formulações. Embora os comprimidos obtidos tenham apresentado características dentro dos limites farmacopéicos, os resultados indicam que variações da concentração de amido provocam diferenças nos diversos parâmetros físicos estudados. Concentração mais alta de amido em pó dá origem, provavelmente, à interação entre os componentes da fórmula, interferindo na liberação in vitro do fármaco. Isto demonstra a importância de se otimizar a concentração dos adjuvantes numa formulação de comprimidos, pois, embora uma pequena variação nesta concentração não exerça efeito significativo no tempo de desintegração, a quantidade de fármaco liberado pode ser substancialmente alterada.
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Epilepsies are neurological disorders characterized by recurrent and spontaneous seizures due to an abnormal electric activity in a brain network. The mesial temporal lobe epilepsy (MTLE) is the most prevalent type of epilepsy in adulthood, and it occurs frequently in association with hippocampal sclerosis. Unfortunately, not all patients benefit from pharmacological treatment (drug-resistant patients), and therefore become candidates for surgery, a procedure of high complexity and cost. Nowadays, the most common surgery is the anterior temporal lobectomy with selective amygdalohippocampectomy, a procedure standardized by anatomical markers. However, part of patients still present seizure after the procedure. Then, to increase the efficiency of this kind of procedure, it is fundamental to know the epileptic human brain in order to create new tools for auxiliary an individualized surgery procedure. The aim of this work was to identify and quantify the occurrence of epilepticform activity -such as interictal spikes (IS) and high frequency oscillations (HFO) - in electrocorticographic (ECoG) signals acutely recorded during the surgery procedure in drug-resistant patients with MTLE. The ECoG recording (32 channels at sample rate of 1 kHz) was performed in the surface of temporal lobe in three moments: without any cortical resection, after anterior temporal lobectomy and after amygdalohippocampectomy (mean duration of each record: 10 min; N = 17 patients; ethic approval #1038/03 in Research Ethic Committee of Federal University of São Paulo). The occurrence of IS and HFO was quantified automatically by MATLAB routines and validated manually. The events rate (number of events/channels) in each recording time was correlated with seizure control outcome. In 8 hours and 40 minutes of record, we identified 36,858 IS and 1.756 HFO. We observed that seizure-free outcome patients had more HFO rate before the resection than non-seizure free, however do not differentiate in relation of frequency, morphology and distribution of IS. The HFO rate in the first record was better than IS rate on prediction of seizure-free patients (IS: AUC = 57%, Sens = 70%, Spec = 71% vs HFO: AUC = 77%, Sens = 100%, Spec = 70%). We observed the same for the difference of the rate of pre and post-resection (IS: AUC = 54%, Sens = 60%, Spec = 71%; vs HFO: AUC = 84%, Sens = 100%, Spec = 80%). In this case, the algorithm identifies all seizure-free patients (N = 7) with two false positives. To conclude, we observed that the IS and HFO can be found in intra-operative ECoG record, despite the anesthesia and the short time of record. The possibility to classify the patients before any cortical resection suggest that ECoG can be important to decide the use of adjuvant pharmacological treatment or to change for tailored resection procedure. The mechanism responsible for this effect is still unknown, thus more studies are necessary to clarify the processes related to it
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Parkinson's disease (PD) is one of the most common neurodegenerative brain disorders and is characterized primarily by a progressive degeneration of dopaminergic neurons nigroestriatais. The main symptoms of this disease are motor alterations (bradykinesia, rigidity, tremor at rest), which can be highly disabling in advanced stages of the condition. However, there are symptomatic manifestations other than motor impairment, such as changes in cognition, mood and sensory systems. Animal models that attempt to mimic clinical features of PD have been used to understand the behavioral and neural mechanisms underlying neurophysiological disturbance of this disease. However, most models promote an intense and immediate motor impairment, consistent with advanced stages of the disease, invalidating these studies for the evaluation of its progressive nature. The administration of reserpine (a monoamine depletor) in rodents has been considered an animal model for studying PD. Recently we found that reserpine (in doses lower than those usually employed to produce the motor symptoms) promotes a memory deficit in an aversive discrimination task, without changing the motor activity. It was suggested that the administration of this drug in low doses can be useful for the study of memory deficits found in PD. Corroborating this data, in another study, acute subcutaneous administration of reserpine, while preserving motor function, led to changes in emotional context-related (but not neutral) memory tasks. The goal of this research was to study the cognitive and motor deficits in rats repeatedly treated with low doses of reserpine, as a possible model that simulates the progressive nature of the PD. For this purpose, 5-month-old male Wistar rats were submitted to a repeated treatment with vehicle or different doses of reserpine on alternate days. Cognitive and motor parameters and possible changes in neuronal function were evaluated during treatment. The main findings were: repeated administration of 0.1 mg / kg of reserpine in rats is able to induce the gradual appearance of motor signs compatible with progressive features found in patients with PD; an increase in striatal levels of oxidative stress and changes in the concentrations of glutamate in the striatum were observed five days after the end of treatment; in animals repeatedly-treated with 0. 1 mg/kg, cognitive deficits were observed only after the onset of motor symptoms, but not prior to the onset of these symptoms; 0.2 mg / kg reserpine repeated treatment has jeopardized the cognitive assessment due to the presence of severe motor deficits. Thus, we suggest that the protocol of treatment with reserpine used in this work is a viable alternative for studies of the progressive appearance of parkinsonian signs in rats, especially concerning motor symptoms. As for the cognitive symptoms, we suggest that more studies are needed, possibly using other behavioral models, and / or changing the treatment regimen
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Lithium (Li) is the first choice to treat bipolar disorder, a psychiatric illness characterized by mood oscillations between mania and depression. However, studies have demonstrated that this drug might influence mnemonic process due to its neuroprotector, antiapoptotic and neurogenic effects. The use of Li in the treatment of cognitive deficits caused by brain injury or neurodegenerative disorders have been widely studied, and this drug shows to be effective in preventing or even alleviating the memory impairment. The effects of Li on anxiety and depression are controversial and the relationship of the effects of lithium on memory, anxiety and depression remain unknown. In this context, this study aims to: evaluate the effects of acute and chronic administration of lithium carbonate in aversive memory and anxiety, simultaneously, using the plus maze discriminative avoidance task (PMDAT); test the antidepressant effect of the drug through the forced swimming test (FS) and analyze brainderived neurotrophic factor (BDNF) expression in structures related to memory and emotion. To evaluation of the acute effects, male Wistar rats were submitted to i.p. administration of lithium carbonate (50, 100 or 200 mg/kg) one hour before the training session (PMDAT) or lithium carbonate (50 or 100 mg/kg) one hour before the test session (FS). To evaluation of the chronic effects, the doses administered were 50 or 100 mg/kg or vehicle once a day for 21 days before the beginning of behavioral tasks (PMDAT and FS). Afterwards, the animals were euthanized and their brains removed and submitted to immunohistochemistry procedure to quantify BDNF. The animals that received acute treatment with 100 and 200 mg/kg of Li did not discriminated between the enclosed arms (aversive and non-aversive) in the training session of PMDAT, showing that these animal did not learned the task. This lack of discrimination was also observed in the test session, showing that the animals did not recall the aversive task. We also observed an increased exploration of the open arms of these same groups, indicating an anxiolytic effect. The same groups showed a reduction of locomotor activity, however, this effect does not seem to be related with the anxiolytic effect of the drug. Chronic treatment with Li did not promote alterations on learning or memory processes. Nevertheless, we observed a reduction of open arms exploration by animals treated with 50 mg/kg when compared to the other groups, showing an anxiogenic effect caused by this dose. This effect it is not related to locomotor alterations since there were no alterations in these parameters. Both acute and chronic treatment were ineffective in the FS. Chronic treatment with lithium was not able to modify BDNF expression in hippocampus, amygdala and pre-frontal cortex. These results suggest that acute administration of lithium promote impairments on learning in an aversive task, blocking the occurrence of memory consolidation and retrieval. The reduction of anxiety following acute treatment may have prevented the learning of the aversive task, as it has been found that optimum levels of anxiety are necessary for the occurrence of learning with emotional context. With continued, treatment the animals recover the ability to learn and recall the task. Indeed, they do not show differences in relation to control group, and the lack of alterations on BDNF expression corroborates this result. Possibly, the regimen of treatment used was not able to promote cognitive improvement. Li showed acute anxiolytic effect, however chronic administration 4 promoted the opposite effect. More studies are necessary to clarify the potential beneficial effect of Li on aversive memory
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This study aimed to apply, thermogravimetriy /derivative Thermogravimetriy (TG/DTG), differential scanning calorimetry (DSC), Differential Thermal Analysis (DTA), to conduct a comparative study on drug reference, generic and whose active principles are similar captopril hydrochlorothiazide, ampicillin, paracetamol, aspirin and mebendazole sold in local pharmacies. Samples of the active ingredients and dosage forms were also characterized by absorption infrared spectroscopy (IR), X-ray diffraction (XRD) and microscopy scanning electron (SEM). The TG / DTG curves showed a general similarity in the thermal behavior of the samples, but also showed the influence of excipients on the thermal stability. The DSC curve of the generic base hydrochlorothiazide showed no peak on the fusion of the drug due to interference of lactose as a diluent, which causes interaction with the active principle causing their degradation before the merger. The DSC curves of the drugs consisting of paracetamol showed reproducibility at the melting point of the active and the other thermal events. The DSC result of binary mixtures involving captopril / magnesium stearate and mebendazole/magnesium stearate showed possible interactions or incompatibilities evidenced by the displacement of the melting point of both drugs. The other mixtures showed no change. The infrared spectra presented were very similar, indicating the presence of functional groups characteristic of the constituents of the samples. The X-ray diffraction showed peaks indicative of crystalline structure of the active ingredients as well as some of the ingredients in the formulation of the drug and the micrographs indicate a general heterogeneity in the size distribution of particles in the samples