Preparação e carcterização de complexos multicomponentes contendo ciclodextrinas e benznidazol

The benznidazole (BNZ) is the only alternative for Chagas disease treatment in Brazil. This drug has low solubility, which restricts its dissolution rate. Thus, the present work aimed to study the BNZ interactions in binary systems with beta cyclodextrin (β-CD) and hydroxypropyl-beta cyclodextrin (HP-β-CD), in order to increase the apparent aqueous solubility of drug. The influence of seven hydrophilic polymers, triethanolamine (TEA) and 1-methyl-2- pyrrolidone (NMP) in benznidazole apparent aqueous solubility, as well as the formation of inclusion complexes was also investigated. The interactions in solution were predicted and investigated using phase solubility diagram methodology, nuclear magnetic resonance of protons (RMN) and molecular modeling. Complexes were obtained in solid phase by spray drying and physicochemical characterization included the UV-Vis spectrophotometric spectroscopy in the infrared region, scanning electron microscopy, X-ray diffraction and dissolution drug test from the different systems. The increment on apparent aqueous solubility of drug was achieved with a linear type (AL) in presence of both cyclodextrins at different pH values. The hydrophilic polymers and 1-methyl-2-pyrrolidone contributes to the formation of inclusion complexes, while the triethanolamine decreased the complex stability constant (Kc). The log-linear model applied for solubility diagrams revealed that both triethanolamine and 1-methyl-2-pyrrolidone showed an action cosolvent (both solvents) and complexing (1-methyl-2-pyrrolidone). The best results were obtained with complexes involving 1-methyl-2-pyrrolidone and hydroxypropylbeta- cyclodextrin, with an increased of benznidazole solubility in 27.9 and 9.4 times, respectively. The complexes effectiveness was proven by dissolution tests, in which the ternary complexes and physical mixtures involving 1-methyl- 2-pyrrolidone and both cyclodextrins investigated showed better results, showing the potential use as novel pharmaceutical ingredient, that leads to increased benznidazole bioavailability

Obtenção e caracterização de complexos de inclusão binários e ternários com praziquantel

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Estudo de compatibilidade e estabilidade térmica do ácido retinóico e hidroquinona por termogravimetria

Retinoic acid (RA) and hydroquinone (HQ) assets are widely used in pharmaceutical and cosmetic formulations, for having depigmenting properties and are largely produced in drugstores. To assist in the development of formulations containing the active RA and HQ National Forms of Brazilian Pharmacopoeia (2005 and 2012 ) proposes formulations with different excipients such as cetyl alcohol (AC), cetostearyl alcohol (ACT), methylparaben (MTP), propyl paraben ( PPB), glycerin (GLY), dipropylene glycol (DPG), imidazolidinil urea ( IMD ), cyclomethicone (CCM ), butylated hydroxytoluene (BHT), octyl stearate (ETO), EDTA, decil oleate (ODC) and hydroxipropymethyl celullose (HPMC). One of the difficulties found in most cosmetic formulations is the large number of incompatibilities between the components of the formulations, so the aim this study was to evaluate thermal stability and interactions between these active pharmaceutical ingredients and excipients. The depigmenting agents were analyzed by DSC and TG and excipients were analyzed by TG. The dynamic thermogravimetric curves were obtained on a SHIMADZU thermobalance, model DTG-60, using an alumina crucible, at the heating rate of 10ºC min-1, in the temperature range of 25-900 ºC, under an atmosphere of nitrogen at 50 mL min-1. The DSC curves were obtained using Shimadzu calorimeter, model DSC-60, using aluminum crucible, at the heating rate of 10ºC min-1, in the temperature range of 25-400ºC. The thermogravimetric and calorimetric curves were analyzed using TASYS software SHIMADZU. In this study no were found interactions between AR and the following excipients: MTP, PPB, IMD, ODC, EDTA, CCM, ETO, HPMC. However, were found interactions with the following excipients: AC, ACT, BHT, GLI and DPG. For HQ were found interactions with IMD and DPG. Interactions remained even changing proportions of the mixtures and the ternary. Thus, the studies conducted with excipients of National Formulary from 2005 and 2012 showed that these new excipients do not interact by thermogravimetry with the active pharmaceutical ingredients of this study

Micropartículas de poli (ácido láctico)/ poloxámero obtids por spray drying para liberação modificada de metotrexatro

New drug delivery systems have been used to increase chemotherapy efficacy due the possible drug resistance of cancer cells. Poly (lactic acid) (PLA) microparticles are able to reduce toxicity and prolong methotrexate (MTX) release. In addition, the use of PLA/poloxamer polymer blends can improve drug release due to changes in the interaction of particles with biological surfaces. The aim of this study was developing spray dried biodegradable MTX-loaded microparticles and evaluate PLA interactions with different kinds of Pluronic® (PLUF127 and PLUF68) in order to modulate drug release. The variables included different drug:polymer (1:10, 1:4.5, 1:3) and polymer:copolymer ratios (25:75, 50:50, 75:25). The precision and accuracy of spray drying method was confirmed assessing drug loading into particles (75.0- 101.3%). The MTX/PLA microparticles showed spherical shape with an apparently smooth surface, which was dependent on the PLU ratio used into blends particles. XRD and thermal analysis demonstrated that the drug was homogeneously dispersed into polymer matrix, whereas the miscibility among components was dependent on the used polymer:copolymer ratio. No new drug- polymer bond was identified by FTIR analysis. The in vitro performance of MTX-loaded PLA microparticles demonstrated an extended-release profile fitted using Korsmeyer- Peppas kinetic model. The PLU accelerated drug release rate possible due PLU leached in the matrix. Nevertheless, drug release studies carried out in cell culture demonstrated the ability of PLU modulating drug release from blend microparticles. This effect was confirmed by cytotoxicity observed according to the amount of drug released as a function of time. Thus, studied PLU was able to improve the performance of spray dried MTX-loaded PLA microparticles, which can be successfully used as carries for modulated drug delivery with potential in vivo application

Efeitos por comparações e por experimento em interações de experimentos fatoriais

Avaliar efeitos de interações é um dos principais objetivos dos experimentos fatoriais. em experimentos com dois fatores A e B, com m e n níveis de cada fator, respectivamente, há m x n possíveis interações e (m-1)(n-1) graus de liberdade associados. Freqüentemente somente parte dessas interações contribui efetivamente para a Soma de Quadrados da Interação e pode ser interessante examiná-las. O uso de nível de significância menos rigoroso para interpretação do efeito da interação por experimento, em relação às demais fontes de variação da análise de variância, pode captar efeitos importantes. Recomenda-se o uso de p = 0,25 para a interpretação do efeito da interação por experimento, mantendo-se o usual p = 0,05 para efeitos por comparações. Mesmo no caso de interações significativas, comparações selecionadas, em lugar de apenas cortes, podem auxiliar a interpretação de interações complexas.

O direito à saúde: a medida do dever do estado de fornecer Medicamentos de dispensação excepcional à sociedade sob a ótica do desenvolvimento

It is a fact that the fundamental rights of citizens are being recognized and guaranteed by the state over time, regardless of the belief that if these rights has always been part of the heritage of subjective individuals, or whether they will be aggregated during the course of human history. In that, emerged the rights of freedom of men and, subsequently, the rights to create a situation of equality between the humans, the so-called social rights. In turn, as these rights known as social, to be implemented, need a positive action by the state, more precisely by the state power whose function is to manage public money and create policies for implementation of fundamental rights. Given this, pay attention to the right to health, was created the Programa de Medicamentos de Dispensação Excepcional, which aims to provide high-cost medicines to citizens Brazilian carriers of serious diseases, such as Alzheimer's and Mal Hepatitis C. Also on the program, it provides a way which will be mandatory that the drugs will be offered in such situations, and does not include a means of updating the list predicted able to monitor the progress of medicine that have been in the interest of the program. Given that, at present it is necessary to mention the recognition of another fundamental right: the right to development, which is the right of access to positive actions being implemented by the State, which are nothing more than public policy, gender which the Programa de Medicamentos de Dispensação Excepcional is kind. Thus, through the search in legislation and doctrine in relation to the theme, this work has the aim to examine the extent of the state to provide exceptional dispensing of medicines. Specifically, if the State in attention to the right to development and the implementation of the right to health, can really list exhaustively the drugs to be provided by the State, and what are the elements guiding this choice and how to control the same

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

Parâmetros de concretização judicial do direito fundamental à saúde no fornecimento de medicamentos

In Brazil, social rights have always been considered secondary legal categories, whose implementation could wait for the pending of political decisions. At the end of the Second World War, International Law emphasizes the protection of human beings, raising his dignity as a legal pillar of the legal orders and one of the main foundations of Constitutions. At the post-positivism Constitutionalism, the realization of social rights receives special attention with the assumption of supremacy and normativity of the Constitutions, while the judiciary participates in the realization of democracy, not only as applicator of laws, but also as the guardian of constitutionality of the acts and administrative omissions, creatively contributing to the constitutional achievement, filling gaps and normative state omissions. In this aspect, the supply of medicines, whose costs can not be supported by the individual, keep a close connection with the right to life, health and dignity of the human being, as the subject of numerous lawsuits directed against the Public Administration. Such phenomenon has caused intense debate regarding judicial activism and legitimacy of these decisions, particularly on the need to define what are the limits and possibilities considering the principle of separation of powers and the principle of reserve of the possible; bieng this the problematic developed in this research. Thus, this research aims to verify the legitimacy of judicial decisions that determines to the Public Administration the compulsory providing of medicine to those who can not afford the cost of their treatment, as well as, contribute to the dogmatic constructions of parameters to be observed by judicial interference. Regarding the methodology, this research has an investigative and descriptive caracter and an theoretical approach based on bibliographical data collection (judicial and doutrine decisions) that received qualitative treatment and dialectical approach. As a result, it is known that the judicial decision that determines the supply of medicines to those individuals who can not afford them with their own resources is legitimate and complies with the democratic principle, not violating the principle of separation of powers and the reserve of the possible, since the judicial decison is not stripped with an uniform and reasonable criteria, failing to contain high burden of subjectivism and witch signifies a possible exacerbation of functions by the judiciary, suffering, in this case, of requirement of legal certainty. It is concluded that the Court decision that determines the government the providing of medicine to those who can not afford the cost of treatment should be based on parameters such as: the protection of human dignity and the minimum existencial principle, the inafastable jurisdiction principle; compliance critique of the possible reserve principle; subsidiarity of judicial intervention; proportionality (quantitative and qualitative) in the content of the decision; the questioning about the reasons for non-delivery of the drug through administrative via; and, finally, the attention not to turn the judiciary into a mere production factor of the pharmaceutical industry, contributing to the cartelization of the right to health

A perda de grupos funcionais em comunidades virtuais: efeito das interações entre espécies e grupos funcionais

High levels of local, regional, and global extinctions has progressively simplified communities in terms of both species and ecosystem functioning. Theoretical models demonstrated that the degree of functional redundancy determines the rates of functional group loss in response to species extinctions. Here, we improve the theoretical predictions by incorporating in the model interactions between species and between functional groups. In this study, we tested the effect of different scenarios of interspecific interactions and effects between functional groups on the resistance to loss of community functional groups. Virtual communities have been built with different distribution patterns of species in functional groups, both with high and low evenness. A matrix A was created to represent the net effect of interspecific interactions among all species, representing nesting patterns, modularity, sensitive species, and dominant species. Moreover, a second matrix B was created to represent the interactions between functional groups, also exhibiting different patterns. The extinction probability of each species was calculated based on community species richness and by the intensity of the interspecific interactions that act upon it and group to which it belongs. In the model, successive extinctions decrease the community species richness, the degree of functional redundancy and, consequently, the number of functional groups that remain in the system. For each scenario of functional redundancy, A, and B, we ran 1000 simulations to generate an average functional extinction curve. Different model assumptions were able to generate remarkable variation on functional extinction curves. More extreme variations occurred when the matrix A and B caused a higher heterogeneity in the species extinction probability. Scenarios with sensitive species, positive or negative, showed a greater variation than the scenarios with dominant species. Nested interactions showed greater variation than scenarios where the interactions were in modules. Communities with maximal functional evenness can only be destabilized by the interactions between species and functional groups. In contrast, communities with low functional evenness can have its resistance either increased or decreased by the interactions. The concentration of positive interactions in low redundancy groups or negative interactions in high redundancy groups was able to decrease the functional extinction rates. In contrast, the concentration of negative interactions in low redundancy groups or positive interactions in high redundancy groups was able to increase the functional extinction rates. This model shows results that are relevant for species priorization in ecosystem conservation and restoration

O papel de interações positivas entre plantas na regeneração de áreas degradadas na caatinga

Conselho Nacional de Desenvolvimento Científico e Tecnológico

O papel das interações no processo de inclusão de crianças com síndrome de Down

La inclusión actual está siendo orientada por diversos principios, tales como la cooperación, aceptación de las diferencias individuales, valoración de cada individuo y convivencia dentro de la diversidad. En esta perspectiva, se entiende la educación como un proceso, en que todos los alumnos con necesidades educativas especiales tienen el derecho de escolarización en el salón de clase general, visando el desarrollo máximo de su potencial. Es en la interacción con los otros que los niños desarrollan efectivamente sus capacidades, aprenden a descubrir al otro como portador de valores y, como consecuencia de esa relación, a tener más confianza en sí mismo. Es por lo tanto necesario que las influencias educativas sean recíprocas y que en la convivencia escolar, puedan ser constantes las relaciones interpersonales. Así, haciendo con que cada niño sea introducido a la vivencia de la ciudadanía, al aprendizaje que va más allá de los contenidos escolares y envolviendo también la construcción de valores, hábitos y actitudes. Con base en estos aspectos, nuestro trabajo tuvo como objetivo la interacción entre niños con síndrome de Down y sus compañeros, en dos clases regulares de una escuela pública em el nível de educación infantil, en la ciudad de Natal/RN. En este sentido, realizamos un estudio de caso con dos niños, envolviendo observación, aplicación de entrevistas y cuestionarios, además de la utilización de la sociometría. Los datos analizados apuntan la existencia de un espíritu de cooperación entre los niños, del respeto a la diversidad y también a sus limitaciones. Estos son valores que están siendo construidos y que son percibidos claramente en lo cotidiano de la escuela. De igual modo, de esta convivência resulta la construcción de vínculos afectivos y sociales entre los niños que presentan el síndrome de Down y sus compañeros, siendo estos similares a los desarrollados entre los niños en general. Sin embargo, se evidencia todavía, la necesidad de un incentivo mayor por parte de la comunidad escolar para que sean establecidos vínculos más significativos

Interações comunicativas entre uma professora e um aluno com transtorno invasivo do desenvolvimento na escola regular

Inclusion of students with autism in regular education settings is a topic that has not been much explored by the national scientific literature. This matter is complex and, due to the extent of various aspects involved, it is essential to delimitate a focus of investigation. The direction taken by this study was to evaluate the effects of an intervention program in the communicative interactions between a student with autism and his teacher in a regular classroom. Data were collected in an elementary private school, located in the city of Natal, Rio Grande do Norte during the 2010 academic school year. The study included a teacher and a non-vocal, 10-year-old student diagnosed with autism. A quasi-experimental A-B research design was employed. During the intervention program the teacher was trained to use Naturalistic Teaching Strategies and Alternative and Augmentative Communication (AAC) resources to increase the frequency of interactions with the student during three classroom routines (entry time, snack and pedagogical activity). The results indicated qualitative and quantitative changes in the interactions of the dyad after the implementation of the intervention program. The student began to use pictograms to communicate with the teacher in two of the three routines investigated. The frequency of AAC use was also observed in the teacher‟s repertoire, especially when the student failed to understand gestures and words. The teacher positively evaluated the intervention program

A dimensão social do desenho: um estudo sobre as interações no processo de (re) construção imagética da criança no Ensino Fundamental

In the historical-cultural perspective, the drawing is processed by means of a shared and complex way, under diverse relations with the other and with the immersed signs of the culture. That is, something constituted by the social interactions and that can modify the structure of the psychological functions, therefore as socialized sign, propitiates the incorporation of the functions socially. In this way, the figuration carrier sensitive and established meanings historically disclosing the shared experiences and the ways of the subject to think and perceive the world. Such reflections gave shape to the main problem of this research: how to think over about the drawing at the school to incide in the reconstruction of the childs imaginative language? Under such perspective, this work deals with the interactions in the production process of the drawing of the children in a context of teach-Iearning of the elementary school having as goal to analyze the interactions established in the cIassroom in the process of production of the drawings; to propose situations of learnings that favor the advance graphical expression of the students; and to identify in the interactive games some relations between body expression and drawing. For its accomplishment, it was opted for the construction process based in the collaborative investigation by the fact to propitiate negotiations, sharing and confrontation of ideas, becoming possible a joint construction of the knowledge. For this research, the researcher and the collaborating teacher, as well as the involved children, become themselves into co-authors of the context studied. As locus of the research, it was chosen a first cycle class, with 30 students, from Municipal School Profª. Emília Ramos (Natal/RN - Brazil), whose election took in account the fact of this school to constitute in a promotional space of reflections and professional development of teachers in service and, at the same time, for presentinglimitations theoretic- methodological in the field of teaching for Arts. In the process of the research, it was perceived that the children with the support of the verbal language formulates meanings on the seen and imagined object, printing lines and forms that if overlap to the physiological aspects of the visual perception. That is, the drawing discloses a reality appraised, enriched for the picked up vision of the image, but the meanings established for the author, or observer who becomes it perceivable and identified. In the systemizing situations, it was observed that the teaching-Iearning process of the drawing, implies a co-construction between teachers and learners. And, moreover, the necessity to interlace emotion and cognition by means of plastic-corporal interactions that foment drawing experiences, whose process concurs for the imagenative reconstruct of the apprentices

Automedicação e guarda de medicamentos por universitários das áreas de saúde e tecnologia

This study aimed to compare self-medication and domestic drug storage among undergraduate students in the areas of health and technology. This is a descriptive study of cross-sectional type and quantitative approach, conducted in a Public University of Natal, Rio Grande do Norte, Brazil. The sample consisted of 300 students of the third year of undergraduate courses at the Center for Health Sciences and Technology Center, selected through a simple random sample. The project was authorized by the Ethics Committee of Federal University of Rio Grande do Norte (CAAE 0137.0.051.000-10). Data collection lasted twelve months and was conducted during the period of study participants, in the university environment. The instrument for data collection was a structured questionnaire consisting of open and closed questions. For data analysis, we used descriptive statistics and applied Fisher s exact test and Chi-square test with adopted level of significance α=5% and 10%. For the variables that correlated with self-medication (p<0.05), we subsequently calculated the odds ratios and confidence intervals. The prevalence of undergraduate students who performed self-medication in the 15 days prior to the collection accounted for 33.7% and, by analyzing each knowledge area, we verified was a higher prevalence of self-medication among students in the technological area (37.3%). The analysis of the socio-demographic characteristics of the participants in this practice revealed a significant difference between the knowledge areas in the income and self-medication variables (p=0.005). General analgesics and antipyretics (N02) represent the therapy group most used in self-medication (57.4%), especially acetaminophen (28.7%), and the main health situations that motivated this practice related to pain, especially headaches (48.5%). Regarding the indication of the drugs used, the majority of students self-medicated themselves on their own (71.3%). As regards to the in-home drug storage, most of the participants had a home pharmacy (88%). By analyzing the socioeconomic characteristics, the variables medical service and home medicine presented a significant difference (p=0.002). General 10 analgesics and antipyretics constituted the medicinal products most found in the home pharmacies, especially acetaminophen. The main room used for the drug storage was the kitchen (36.4%), most students kept these products in boxes of different materials (38.6%) and the medicines stored at home of most of the participants were not easily accessible to children (75%). The results reinforce the need to develop strategies, from the reality found, aiming to encourage and implement educational and preventive activities with undergraduate students on the importance of proper self-medication and in-home drug storage. Despite the sample in our study is relatively small, not representative for the whole country, we believe that, at national level, the panorama of the subject does not present major differences

Estratégias de avaliação de desempenho dos propagandistas de medicamentos utilizados pela indústria farmacêutica no nordeste do Brasil

A Indústria Farmacêutica é uma das mais competitivas indústrias do mundo contemporâneo, e um dos seus principais desafios está na comercialização de seus medicamentos, que na sua maioria depende da prescrição médica. O objetivo deste estudo é identificar as estratégias de avaliação de desempenho utilizadas pela Indústria Farmacêutica de origem multinacional que atua no nordeste Brasileiro e o papel dos seus gerentes, para avaliar os propagandistas vendedores de medicamentos. Para tanto, buscouse reunir elementos para uma abordagem satisfatória que contemple a complexidade da temática pesquisada: Avaliação de Desempenho, Estratégias da Indústria Farmacêutica, Propaganda Médica e Competências dos Propagandistas de Medicamentos. A temática justifica-se em razão da importância estratégica dos propagandistas de medicamentos para a indústria farmacêutica, que é uma das indústrias que mais investe em pesquisa na atualidade, e contribui para melhorar a qualidade de vida e a saúde humana. A metodologia é caracterizada como um survey, de natureza quali-quantitativa. O objeto de estudo é composto pelas empresas farmacêuticas multinacionais de origem Americanas, Europeias e Asiáticas, associadas à INTERFARMA que atuam no Nordeste do Brasil. A coleta de dados foi realizada através de um questionário fechado (instrumento de pesquisa), composto por 5 perguntas fechadas que abordam a temática central dessa dissertação, 27 afirmativas para medir a concordância(escala likert) e 1 tabela contendo 46 competências, aplicado junto a gerentes da indústria farmacêutica. A análise dos dados foi feita por meio das técnicas de estatística descritiva e uma análise quantitativa para estabelecer o Ranking Médio (RM) para a parte do questionário que utilizou escala tipo Likert de 5 pontos para mensurar o grau de concordância dos respondestes. Através dos resultados desta pesquisa foi possível identificar as estratégias de avaliação de desempenho, utilizadas pelas empresas farmacêuticas, que atuam no Nordeste do Brasil, na gestão dos propagandistas vendedores de medicamentos, e identificar as competências essenciais dos propagandistas de medicamentos, na percepção dos gestores. Os resultados demonstraram que a Indústria Farmacêutica desenvolve e utiliza várias estratégias para medir e avaliar o desempenho dos propagandistas de medicamentos no Brasil, assim como em outros países, e que na percepção dos gerentes da Indústria Farmacêutica existem competências consideradas essenciais ao bom desempenho profissional dos propagandistas de medicamentos da indústria farmacêutica, contribuindo de para avanço do conhecimento deste tema