Avaliação citológica em base líquida de fármacos moduladores estrogênicos

Hormone therapy is an important tool in the treatment of breast cancer and tamoxifen represents one of the most important drugs used in this type of treatment. Recently other drugs based on the inhibition of aromatase had been developed, this enzyme is responsible for the synthesis of estrogenic esteroids from the androgenic ones. The objective of this study would be the development of a quantitative cytological model of murine estral analysis that allowed the characterization of different hormone drugs effect over vaginal epithelium. The technique of monochromatic staining with Evans blue (C.I. 23860) showed to be efficient in the qualitative and quantitative classification of the cycle. It had been observed differences in the cytological standard of animals submitted to the studied drugs; tamoxifen presented a widening of phases of lesser maturation (diestrais), while anastrozole and exemestane increased the duration of the phases of larger maturation (estrais). The data were analysed through a cubical non linear regression (spline) which allowed a better characterization of the drugs, suggesting a proper cytological profile to the antagonism of the estrogen receptor (tamoxifen), aromatase competition (anastrozole) and inhibition of the enzyme (exemestane)

Fatores preditivos da dor em pacientes submetidos à cirurgia cardíaca

A identificação de fatores que interferem na dor pós-operatória é útil para minimizar o sofrimento desnecessário e favorecer a uma intervenção analgésica adequada, evitando generalizações nas condutas terapêuticas. O propósito dessa investigação foi identificar os fatores preditivos da dor em pacientes submetidos à cirurgia cardíaca e a relação existente entre dor, analgesia e personalidade. Trata-se de um estudo prospectivo e analítico, aprovado pelo comitê de ética da UFRN (175/06), o qual proporcionou uma abordagem multidisciplinar ao envolver áreas distintas como: fisioterapia, psicologia, médica e enfermagem (interdisciplinaridade) na elucidação do objeto de estudo relacionado a fatores preditivos da dor. Para caracterização geral dos pacientes foi utilizada uma ficha de avaliação fisioterapêutica; a dor pós-operatória foi avaliada pela escala numérica de dor e questionário para dor McGill e o Inventário Millon de Estilos de Personalidade (MIPS) foi utilizado para identificar e avaliar as manifestações das características comportamentais e de personalidade. Foram acompanhados, do 1º ao 5º dia de pós-operatório (DPO), 160 pacientes submetidos à cirurgia cardíaca, 57,5% do sexo masculino, com idade média de 56,8±14,4 anos, sendo incluídos no estudo aqueles que se queixaram de dor no pós-operatório em pelo menos um dos dias de avaliação e assinaram termo de concentimento livre e esclarecido (TCLE). Os dados foram submetidos ao teste Qui-quadrado, regressão logística multivariada, teste de correlação de Spearman, teste t e ANOVA. Ao serem submetidos à análise de regressão foram encontrados seis fatores preditivos da dor: tempo cirúrgico > 3 horas, dreno mediastinal e lateral, tosse, vômitos, tempo de dreno > 24 horas e sexo feminino. Estes fatores apresentaram uma correlação positiva e significava com a intensidade dolorosa referida pelos pacientes na escala numérica de dor e os pacientes que apresentaram mais fatores preditivos da dor referiram mais dor. 23 Já em relação ao McGill não se obteve diferença significativa entre os pacientes com mais e menos fatores preditivos. Observou-se que foram administrados diferentes tipos de analgésicos, isolados ou associados, sendo estes: paracetamol, paracetamol associado à codeína, dipirona, tramadol, toradol e tilatil. A percepção dolorosa apresentou magnitudes variando de leve a moderada do 1º ao 5º DPO e ao ser relacionada com as características de personalidade, nos pacientes com menos dor, observou-se os fatores: preservação, individualismo, introversão e os com mais dor foram: proteção, extroversão, retraimento, discrepância, afetividade, acomodação, comunicabilidade e firmeza. Evidenciou-se que o comportamento doloroso pós-cirurgia cardíaca é multifatorial e que a determinação da existência de fatores preditivos da dor permite ao profissional da área de saúde fazer o uso adequado dos analgésicos, haja vista que o alívio da dor é responsabilidade de todos os profissionais da saúde. Os aspectos psicológicos enquanto características de personalidade podem influenciar padrões de comportamento como os observados.

Síntese e caracterização do poli(ácido láctico) para potencial uso em sistemas de liberação controlada de fármacos

With the advances in medicine, life expectancy of the world population has grown considerably in recent decades. Studies have been performed in order to maintain the quality of life through the development of new drugs and new surgical procedures. Biomaterials is an example of the researches to improve quality of life, and its use goes from the reconstruction of tissues and organs affected by diseases or other types of failure, to use in drug delivery system able to prolong the drug in the body and increase its bioavailability. Biopolymers are a class of biomaterials widely targeted by researchers since they have ideal properties for biomedical applications, such as high biocompatibility and biodegradability. Poly (lactic acid) (PLA) is a biopolymer used as a biomaterial and its monomer, lactic acid, is eliminated by the Krebs Cycle (citric acid cycle). It is possible to synthesize PLA through various synthesis routes, however, the direct polycondensation is cheaper due the use of few steps of polymerization. In this work we used experimental design (DOE) to produce PLAs with different molecular weight from the direct polycondensation of lactic acid, with characteristics suitable for use in drug delivery system (DDS). Through the experimental design it was noted that the time of esterification, in the direct polycondensation, is the most important stage to obtain a higher molecular weight. The Fourier Transform Infrared (FTIR) spectrograms obtained were equivalent to the PLAs available in the literature. Results of Differential Scanning Calorimetry (DSC) showed that all PLAs produced are semicrystalline with glass transition temperatures (Tgs) ranging between 36 - 48 °C, and melting temperatures (Tm) ranging from 117 to 130 °C. The PLAs molecular weight characterized from Size Exclusion Chromatography (SEC), varied from 1000 to 11,000 g/mol. PLAs obtained showed a fibrous morphology characterized by Scanning Electron Microscopy (SEM)

O Tratamento com a fluoxetina (mas não com outros farmacos antidepressivo e ansioíiticos) reverte o déficit de memória aversiva causado por estresse agudo de contenção em camundongos

The physiologist H. Selye defined stress as the nonspecific response of the body to any factors that endanger homeostasis (balance of internal environment) of the individual. These factors, agents stressors, are able to activate the Hypothalamic-Pituitary-Adrenal (HPA) axis, thus resulting in the physiological responses to stress by the release of glucocorticoids that leads to psychophysiological changes, including effects on cognitive functions such as learning and memory. When this axis is acutely stimulated occurs a repertoire of behavioral and physiological changes can be adaptive to the individual. Notwithstanding, when the HPA axis is chronically stimulated, changes may favor the development of, such as anxiety disorders. Some drugs used in the clinic for the treatment of anxiety disorders these can exert effects on cognitive function, on the HPA axis and on the anxiety. In this context, the aim of our study was to investigate the effects of administration i.p. acute of diazepam (DZP, 2 mg/kg), buspirone (BUS, 3 mg/kg), mirtazapine (MIR, 10 mg/kg) and fluoxetine (FLU, 10 mg/kg) in male mice submitted to acute restraint stress, and evaluated using plus-maze discriminative avoidance task (PMDAT), which simultaneously evaluates parameters such as learning, memory and anxiety. Our results demonstrated that (1) the administration of DZP and BUS, but not FLU, promoted anxiolytic effects in animals; (2) administration mirtazapine caused sedative effect to animals; (3) in the training session, the animals treated with BUS, MIR and FLU learned the task, on the other hand DZP group showed impairment in learning; (4) in the test session, animals treated with DZP, BUS, and MIR showed deficits in relation to discrimination between the enclosed arms, aversive versus non-aversive arm, demonstrating an impairment in memory, however, animals treated with FLU showed no interference in the retrieval of this memory; (5) acute stress did not interfere in locomotor activity, anxiety, or learning on the learning task, but induced impairment in retrieval memory, and the group treated with FLU did not demonstrated this deficit of memory . These results suggest that acute administration of drugs with anxiolytic and antidepressant activity does not interfere with the learning process this aversive task, but impair its retrieval, as well as the acute restraint stress. However, the antidepressant fluoxetine was able to reverse memory deficits promoted by acute stress, which may suggest that modulation, even acutely serotonergic neurotransmission, by selectively inhibiting the reuptake of this neurotransmitter, interferes on the process of retrieval of an aversive memory

Síntese e caracterização do poli(ácido láctico) para potencial uso em sistemas de liberação controlada de fármacos

With the advances in medicine, life expectancy of the world population has grown considerably in recent decades. Studies have been performed in order to maintain the quality of life through the development of new drugs and new surgical procedures. Biomaterials is an example of the researches to improve quality of life, and its use goes from the reconstruction of tissues and organs affected by diseases or other types of failure, to use in drug delivery system able to prolong the drug in the body and increase its bioavailability. Biopolymers are a class of biomaterials widely targeted by researchers since they have ideal properties for biomedical applications, such as high biocompatibility and biodegradability. Poly (lactic acid) (PLA) is a biopolymer used as a biomaterial and its monomer, lactic acid, is eliminated by the Krebs Cycle (citric acid cycle). It is possible to synthesize PLA through various synthesis routes, however, the direct polycondensation is cheaper due the use of few steps of polymerization. In this work we used experimental design (DOE) to produce PLAs with different molecular weight from the direct polycondensation of lactic acid, with characteristics suitable for use in drug delivery system (DDS). Through the experimental design it was noted that the time of esterification, in the direct polycondensation, is the most important stage to obtain a higher molecular weight. The Fourier Transform Infrared (FTIR) spectrograms obtained were equivalent to the PLAs available in the literature. Results of Differential Scanning Calorimetry (DSC) showed that all PLAs produced are semicrystalline with glass transition temperatures (Tgs) ranging between 36 - 48 °C, and melting temperatures (Tm) ranging from 117 to 130 °C. The PLAs molecular weight characterized from Size Exclusion Chromatography (SEC), varied from 1000 to 11,000 g/mol. PLAs obtained showed a fibrous morphology characterized by Scanning Electron Microscopy (SEM)

Avaliação da efetividade de estratégias não farmacológicas para o alívio da dor de parturientes na fase ativa do período de dilatação no trabalho de parto

This study was aim to evaluate the effectiveness of strategies non pharmacological for the relief of the intensity of the parturient pain in the phase activates of the dilation period in the labor. Is a clinic rehearse of the type therapeutic intervention before and after" with a quantitative approach, accomplished in the Humanized Unit of Childbirth of the Maternity Januário Cicco School of the Federal University of Rio Grande do Norte, in Natal/RN, whit 130 parturient, being 30 in the pre-test of the strategies and 100 in the application of the strategies non pharmacological combined (breathing exercises, muscular relaxation and lombossacral massage) and isolated (shower bath in a normal temperature). We used the visual analogical scale to evaluate the intensity of the pain of the study parturient before and after" to the application of the strategies in the phases of acceleration, maximum inclination and desaceleration in the phase activates of dilation period in the labor. The principal results showed that the majority of the study parturient was between 20 to 30 years old (60%); with incomplete fundamental teaching (85%); family income until 2 minimum wages (74%); 78% had a companion and these, 44% were the own husband. The oxytocin was administered in the parturient during the phase activates of the labor in 81% of the cases and only 15% these women didn´t reciev anything medication. We verified significant relief (ρ=0.000) of intensity of the pain of the study parturient after application of the strategies non pharmacological combined and isolated. We concluded that the strategies non pharmacological combined and isolated were effective in the relief of the pain of the study parturient in the phase activates de labor

Novos sistemas de liberação de fármacos à base de xilana

The aim of this work was to perform the extraction and characterization of xylan from corn cobs and prepare xylan-based microcapsules. For that purpose, an alkaline extraction of xylan was carried out followed by the polymer characterization regarding its technological properties, such as angle of repose, Hausner factor, density, compressibility and compactability. Also, a low-cost and rapid analytical procedure to identify xylan by means of infrared spectroscopy was studied. Xylan was characterized as a yellowish fine powder with low density and poor flow properties. After the extraction and characterization of the polymer, xylan-based microcapsules were prepared by means of interfacial crosslinking polymerization and their characterization was performed in order to obtain gastroresistant multiparticulate systems. This work involved the most suitable parameters of the preparation of microcapsules as well as the study of the process, scale-up methodology and biological analysis. Magnetic nanoparticles were used as a model system to be encapsulated by the xylan microcapsules. According to the results, xylan-based microcapsules were shown to be resistant to several conditions found along the gastrointestinal tract and they were able to avoid the early degradation of the magnetic nanoparticles

Sistemas microemulsionados como carreador lipídico para fármacos insolúveis

Several pharmaceutical products have been developed in recent years aiming to enhance the treatment of diseases by increasing the effectiveness of drugs. Many of these new products are based on new drug delivery systems. Among these, microemulsions, which were first studied in 1943 by Hoar and Schulman, is of great interest. Microemulsion can be defined as a thermodynamically stable, isotropic, translucent and transparent system of two immiscible liquids stabilized by a surfactant film located in the oil / water interface. The aim os this work was the incorporation of Amphotericin B and Simvasatin to a microemulsion system and analyzes its physicochemical properties and their therapeutical activity when incorporated into this system. Some very promising results were achieved as the reduction of the toxicity and maintenance of the efficacy of the Amphotericin B incorpored into a microemulsion, which was demonstrated in the in vitro pharmacotoxicological study. As for the incorporation of Simvastatin in microemulsion, it was observed a significant improvement in the potential antiinflammatory and anti-infective properties when the system was use to treat infected wounds (simvastatin pleiotropic effects). Therefore, it can be concluded that the incorporation of these drugs into microemulsion system reveal the potential of microemulsions as a promising and novel dosage form, qualifying them for future trials in order to make them available in the pharmaceutical market

Atividade física e outros fatores associados à função sexual em mulheres de meia idade

Este estudo teve por objetivo avaliar os fatores associados à disfunção sexual em mulheres de meia idade. Realizou-se um estudo descritivo transversal, que compreendeu 370 mulheres, entre 40 a 65 anos, atendidas nas Unidades Básicas de Saúde de cada distrito sanitário (Norte, Sul, Leste e Oeste) da cidade de Natal, no estado do Rio Grande do Norte, Brasil. Para avaliar a função sexual utilizou-se o Female Sexual Function Index (FSFI). A sintomatologia climatérica foi avaliada por meio do Menopause Rating Scale (MRS). O Índice de Blatt-Kupperman (IMBK) foi utilizado para avaliação quantitativa global da ocorrência de sintomas/queixas. A atividade física foi avaliada pelo questionário International Physical Activity Questionnaire - IPAQ (versão curta). A avaliação da qualidade de vida geral se deu pelo WHOQOL-Bref. A análise estatística foi realizada utilizando o programa estatístico MINITAB version16. Além de análises descritivas das variáveis categorizadas, utilizou-se o teste qui-quadrado de Person com o intuito de verificar possíveis associações entre as variáveis sociodemográficas, comportamentais, clínicas, níveis de atividade física, sintomatologia climatérica, qualidade de vida e a função sexual das mulheres estudadas. Desenvolveu-se a regressão logística para verificar a influência dessas variáveis sobre a disfunção sexual. Considerou-se o nível de significância de 5% para todos os testes. Os resultados mostraram que a média de idade das mulheres estudadas foi de 49,8 (±8,1) anos. Do total dessas mulheres, 67% apresentaram disfunção sexual. Observou-se que 54,5% delas se encontravam na pré-menopausa. Avaliando a influência das variáveis sobre a função sexual; faixa etária (56-65) (p<0,001), estado civil (divorciada/separada) (p < 0,001), escolaridade (baixa) (p=0,017), menopausa (p < 0,001), histerectomia (p = 0,016), nível de atividade física (sedentária) (p=0,002), sintomas do climatério (forte) (p<0,001) e qualidade de vida (baixa) (p<0,001), estiveram associados à disfunção sexual em mulheres de meia idade. Concluiu-se neste estudo que fatores sociodemográficos, clínicos, comportamentais, níveis de atividade física, sintomatologia climatérica e qualidade de vida influenciam significativamente a função sexual na mulher de meia idade

Desenvolvimento de sistemas magnéticos com potencialidades terapêuticas para vetorização de fármacos

Magnetic targeting is being investigated as a means of local delivery of drugs, combining precision, minimal surgical intervention, and satisfactory concentration of the drug in the target region. In view of these advantages, it is a promising strategy for improving the pharmacological response. Magnetic particles are attracted by a magnetic field gradient, and drugs bound to them can be driven to their site of action by means of the selective application of magnetic field on the desired area. Helicobacter pylori is the commonest chronic bacterial infection. The treatment of choice has commonly been based upon a triple therapy combining two antibiotics and an anti-secretory agent. Furthermore, an extended-release profile is of utmost importance for these formulations. The aim of this work was to develop a magnetic system containing the antibiotic amoxicillin for oral magnetic drug targeting. First, magnetic particles were produced by coprecipitation of iron salts in alkaline medium. The second step was coating the particles and amoxicillin with Eudragit® S-100 by spray-drying technique. The system obtained demonstrated through the characterization studies carried out a possible oral drug delivery system, consisting in magnetite microparticles and amoxicillin, coated with a polymer acid resistant. This system can be used to deliver drugs to the stomach for treatment of infections in this organ. Another important finding in this work is that it opens new prospects to coat magnetic microparticles by the technique of spray-drying.

Desenvolvimento de microemulsões liofilizadas como um potencial sistema de liberação de fármacos usando planejamento experimental fatorial

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Influência de fármacos lipofílicos na estabilidade de emulsões de uso terapêutico

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Otimização evalidação de métodos analíticos para a determinação simultânea de tuberculostáticos (4-FDC) por CLAE/DAD e CLUE/ DAD

Tuberculosis is a serious disease, but curable in practically 100% of new cases, since complied the principles of modern chemotherapy. Isoniazid (ISN), Rifampicin (RIF), Pyrazinamide (PYR) and Chloride Ethambutol (ETA) are considered first line drugs in the treatment of tuberculosis, by combining the highest level of efficiency with acceptable degree of toxicity. Concerning USP 33 - NF28 (2010) the chromatography analysis to 3 of 4 drugs (ISN, PYR and RIF) last in average 15 minutes and 10 minutes more to obtain the 4th drug (ETA) using a column and mobile phase mixture different, becoming its industrial application unfavorable. Thus, many studies have being carried out to minimize this problem. An alternative would use the UFLC, which is based with the same principles of HPLC, however it uses stationary phases with particles smaller than 2 μm. Therefore, this study goals to develop and validate new analytical methods to determine simultaneously the drugs by HPLC/DAD and UFLC/DAD. For this, a analytical screening was carried out, which verified that is necessary a gradient of mobile phase system A (acetate buffer:methanol 94:6 v/v) and B (acetate buffer:acetonitrile 55:45 v/v). Furthermore, to the development and optimization of the method in HPLC and UFLC, with achievement of the values of system suitability into the criteria limits required for both techniques, the validations have began. Standard solutions and tablets test solutions were prepared and injected into HPLC and UFLC, containing 0.008 mg/mL ISN, 0.043 mg/mL PYR, 0.030 mg.mL-1 ETA and 0.016 mg/mL RIF. The validation of analytical methods for HPLC and UFLC was carried out with the determination of specificity/selectivity, analytical curve, linearity, precision, limits of detection and quantification, accuracy and robustness. The methods were adequate for determination of 4 drugs separately without interfered with the others. Precise, due to the fact of the methods demonstrated since with the days variation, besides the repeatability, the values were into the level required by the regular agency. Linear (R> 0,99), once the methods were capable to demonstrate results directly proportional to the concentration of the analyte sample, within of specified range. Accurate, once the methods were capable to present values of variation coefficient and recovery percentage into the required limits (98 to 102%). The methods showed LOD and LOQ very low showing the high sensitivity of the methods for the four drugs. The robustness of the methods were evaluate, facing the temperature and flow changes, where they showed robustness just with the preview conditions established of temperature and flow, abrupt changes may influence with the results of methods

Avaliação da argila atapulgita para potencial uso como excipiente farmacêutico em formas sólidas

Clays are natural materials that have great potential for use as excipients for solid dosage forms. Palygorskite is a type of clay that has hydrophilic properties as well as a large surface area, which could contribute to the dissolution of drugs. Thus, the present study aims to evaluate the use of palygorskite clay, from Piaui (Northeast region of Brazil), as a pharmaceutical excipient for solid dosage forms, using rifampicin and isoniazid as the model drugs. The former is a poorly soluble drug often associated with isoniazid for tuberculosis treatment. Palygorskite was characterized by X-ray diffraction (XRD), X-ray fluorescence (XRF), particle size, transmission electron microscopy (TEM), scanning electron microscopy (SEM) and specific surface area (BET). The rheological and technological properties of palygorskite were determined and compared to those of talc, magnesium stearate and Aersosil 200. Mixtures between drugs and palygorskite were analyzed by differential scanning calorimetry (DSC), thermogravimetric analysis (TG) combined with thermal analysis (DTA) and Fourier Transform Infrared Spectroscopy (FT-IR), where the results were compared with those of the individual compounds. In addition, dissolution studies of solid dispersions and capsules containing the drugs, mixed with either palygorskite or a mixture of talc and magnesium stearate, were performed. The results showed that palygorskite has small particles with a high surface area. Its rheological characteristics were better than those of others commonly used glidants and lubricants. There was no interaction between palygorskite and the drugs (rifampicin and isoniazid). Among the dispersions studied, the mixture with palygorskite (5%) showed the highest drug dissolution when compared to other excipients. The dissolution of the rifampicin capsules containing palygosrkite was faster in higher concentrations. However, these differences were statistically different only in the first minutes of the dissolution experiment. The dissolution profile of isoniazid was also statistically different on the initial part of the experiment. The formulations prepared with isoniazid and palygorskite showed higher drug dissolution, but it was in descending order of concentration. According to these results, the palygorskite clay used in this study has great potential for application as an excipient for solid dosage forms

O direito à saúde e a política nacional de atenção oncológica: uma análise a partir da crescente judicialização dos medicamentos antineoplásicos

The 1988 Federal Constitution of Brazil by presenting the catalog of fundamental rights and guarantees (Title II) provides expressly that such rights reach the social, economic and cultural rights (art. 6 of CF/88) as a means not only to ratify the civil and political rights, but also to make them effective and practical in the life of the Brazilian people, particularly in the prediction of immediate application of those rights and guarantees. In this sense, health goes through condition of universal right and duty of the State, which should be guaranteed by social and economic policies aimed at reducing the risk of disease and other hazards, in addition to ensuring universal and equal access to actions and services for its promotion, protection and recovery (Article 196 by CF/88). Achieving the purposes aimed by the constituent to the area of health is the great challenge that requires the Health System and its managers. To this end, several policies have been structured in an attempt to establish actions and services for the promotion, protection and rehabilitation of diseases and disorders to health. In the mid-90s, in order to meet the guidelines and principles established by the SUS, it was established the Política Nacional de Atenção Oncológica PNAO, in an attempt to sketch out a public policy that sought to achieve maximum efficiency and to be able to give answers integral to effective care for patients with cancer, with emphasis on prevention, early detection, diagnosis, treatment, rehabilitation and palliative care. However, many lawsuits have been proposed with applications for anticancer drugs. These actions have become very complex, both in the procedural aspects and in all material ones, especially due to the highcost drugs more requested these demands, as well as need to be buoyed by the scientific evidence of these drugs in relation to proposed treatments. The jurisprudence in this area, although the orientations as outlined by the Parliament of Supreme Court is still in the process of construction, this study is thus placed in the perspective of contributing to the effective and efficient adjudication in these actions, with focus on achieving the fundamental social rights. Given this scenario and using research explanatory literature and documents were examined 108 lawsuits pending in the Federal Court in Rio Grande do Norte, trying to identify the organs of the Judiciary behave in the face of lawsuits that seeking oncology drugs (or antineoplastic), seeking to reconcile the principles and constitutional laws and infra constitutional involving the theme in an attempt to contribute to a rationalization of this judicial practice. Finally, considering the Rational Use of health demands and the idea of belonging to the Brazilian people SUS, it is concluded that the judicial power requires ballast parameters of their decisions on evidence-based medicine, aligning these decisions housing constitutional principles that the right to health and the scientific conclusions of efficacy, effectiveness and efficiency in oncology drugs, when compared to the treatments offered by SUS