Nanotechnological delivery systems for the oral administration of active molecules: Polymeric microparticles and microemulsions applied to anti-inflammatory and anti-infectious drugs

This thesis was devoted to the development of innovative oral delivery systems for two different molecules. In the first part, microparticles (MPs) based on xylan and Eudragit® S- 100 were produced and used to encapsulate 5-aminosalicylic acid for colon delivery. Xylan was extracted from corn cobs and characterized in terms of its physicochemical, rheological and toxicological properties. The polymeric MPs were prepared by interfacial cross-linking polymerization and spray-drying and characterized for their morphology, mean size and distribution, thermal stability, crystallinity, entrapment efficiency and in vitro drug release. MPs with suitable physical characteristics and satisfactory yields were prepared by both methods, although the spray-dried systems showed higher thermal stability. In general, spraydried MPs would be preferable systems due to their thermal stability and absence of toxic agents used in their preparation. However, drug loading and release need to be optimized. In the second part of this thesis, oil-in-water microemulsions (O/W MEs) based on mediumchain triglycerides were formulated as drug carriers and solubility enhancers for amphotericin B (AmB). Phase diagrams were constructed using surfactant blends with hydrophiliclipophilic balance values between 9.7 and 14.4. The drug-free and drug-loaded MEs presented spherical non-aggregated droplets around 80 and 120 nm, respectively, and a low polydispersity index. The incorporation of AmB was high and depended on the volume fraction of the disperse phase. These MEs did not reduce the viability of J774.A1 macrophage-like cells for concentrations up to 25 μg/mL of AmB. Therefore, O/W MEs based on propylene glycol esters of caprylic acid may be considered as suitable delivery systems for AmB

Tratamento de fístulas enterocutâneas através de sistema a vácuo com alta pressão e dieta oral normal

Enterocutaneous fistulas are associated with prolonged hospital stay, high morbidity/mortality, and increase in hospital costs. This study aims to describe the use of a vacuum system and normal oral diet in dealing with this problem. Methods: Seventy-four consecutive patients with recent and defined external postoperative fistulas were analyzed. Abdominal imaging was used to exclude abscess and distal obstruction. The fistula tract was sealed with Foley catheter, connected to a negative pressure flask, changed daily for 5, 10 or 15 days, as necessary. Normal oral diet was permitted. Results: No patient died. Serum albumin and transferrin showed significantly higher levels at the end of treatment than at the beginning. The moderate and low-output fistulas had the best results (97% closed). Forty-eight (65%) fistulas closed after five days, 16(22%) after 10 days and 4(5%) after 15 days. Treatment failed in 6(8%) patients, who subsequently underwent surgery. Only one patient with low-output did not close her fistula. The cost of the treatment was US$ 41.75/day and it was considered cost effective. Conclusions: The vacuum system demonstrated good results in the treatment of fistulas. It included simplicity, low cost, short hospital stay, absence of skin breakdown, normal eating, good nutrition and activity patterns

Avaliação do estado nutricional relativo ao selênio e da expressão gênica de selenoproteínas em pacientes com aterosclerose tratados com estatinas

The aim of this study was to determine the effects of the use of rosuvastatin in patients with atherosclerosis, in relation to blood parameters of selenium and selenoproteins, and also observe possible changes in gene expression of selenoproteins in these patients. The sample consisted of 27 adult and elderly patients with a clinical diagnosis of coronary artery disease undergoing angioplasty, treated at Natal Hospital Center hospital, Natal, RN. Patients were treated with rosuvastatin 10 mg/day during four months. Anthropometric variables such as body mass index (BMI) and Waist circumference (WC) were measured before and after treatment, as well as lipid profile, blood glucose and liver enzymes (AST and ALT). The diet of the patients was also analyzed using 24-hour diet recall. We analyzed the concentrations of selenium in plasma and erythrocytes, and also the activity of Glutathione Peroxidase and gene expression by Real Time PCR of selenoproteins GPx1, SelP1 and SelN1. Patients had mean age of 61.0 ± 9.4 years, 59.3% were men and 40.7% were women. After four months of treatment there was significant reduction of CA and, according to BMI, most were overweight. The intake of macronutrients, cholesterol, polyunsaturated fatty acids, monounsaturated and saturated was adequate, but the energy and fiber intake was below the recommendations. Regarding the selenium intake was observed a high prevalence of inadequacy. As expected, after treatment with rosuvastatin, a significant reduction in total cholesterol, LDL and glucose, which was not observed for HDL. Selenium concentrations in plasma and erythrocytes showed no changes, keeping within the established cutoffs. We observed a significant increase in GPx enzyme activity and mRNA expression of GPX1 and SEPN1, but not for gene SEPP1. Thus, it was found that treatment with rosuvastatin did not reduce the expression of selenoproteins. More studies are needed to clarify the effects of rosuvastatin on gene expression of selenoproteins in patients with atherosclerosis

Avaliação do status de zinco e da expressão gênica de metalotioneínas em pacientes com aterosclerose tratados com rosuvastatina

The study had as objective to evaluate the zinc status by means of dietary intake, zinc in plasma and in erythrocytes and the metallothionein gene expression in patients with atherosclerosis in use of rosuvastatin. The research involved 27 adult and elderly patients of both genders with atherosclerosis that were treated with rosuvastatin (10mg/day) during 4 months. We performed the dosage of lipids, glucose, AST and ALT, ultrasensitive C-reactive protein (hsCRP), plasmatic and erythrocyte zinc and 1 and 2 metallothionein gene expression. The assessment of body mass index (BMI) and abdominal circumference (AC) was performed, besides the analysis of dietary intake of patients. The majority of the evaluated patients presented overweight, before and after the treatment, with no significant difference between the times of the study. It was identified that the AC was significantly reduced in the group (p<0.05) after the intervention. The majority of the patients had intake below the recommendation of calories and fibers and above recommendation of proteins. The mono and polyunsaturated fats were adequate for the majority of the patients, however, the saturated fat and cholesterol were consumed in excess by a great part of the individuals. The intake of zinc was inadequate, being noticed an inadequacy of 100% in the male gender and of 84% in the female. After the treatment with rosuvastatin there was a significant reduction in the total cholesterol (TC) and LDL-c (p<0.01) and no alterations were observed in the HDL-c and triacylglycerols. It was also verified that the reduction of glycemia (p<0.05) and of hsCRP (p<0.01). The analysis did not demonstrate significant differences in the plasmatic and erythrocyte zinc concentration after the treatment. There was, after the treatment, reduction of the MT1F gene (p<0.05) without, however, occurring significant alterations in the MT2A gene. The treatment with rosuvastatin was effective in the reduction of TC and LDL-c, and promoted the reduction of inflammatory marker hsCRP. The zinc in the plasma and erythrocyte was not altered by the use of the medication and there was a reduction in the MT1F gene, possibly due to the reduction of inflammation. The majority of patients presented inadequate intake of zinc and this inadequacy did not have relation with the mineral parameters in plasma and erythrocytes or with the metallothionein gene expression

Características genotípicas e fenotípicas de Candida Albicans isoladas da cavidade bucal de pacientes transplantados renais com ênfase na ação do extrato bruto de Eugenia uniflora em fatores de virulência

Candida albicans is a diploid yeast that in some circumstances may cause oral or oropharyngeal infections. The investigation of natural products is mandatory for the discovery of new targets for antifungal drugs development. This study aimed to determine the genotypes of 48 clinical isolates of C. albicans obtained from the oral cavity of kidney transplant patients from two distinct geographic regions of Brazil. In addition, we investigated three virulence factors in vitro: phospholipase activity, morphogenesis and the ability to evade from polymorphonuclear neutrophils. The expression of these virulence factors in vitro was also investigated in the presence of the crude extract of Eugenia uniflora. The genotype A was the most prevalent (30 isolates; 62.5%), followed by genotype C (15 isolates; 31.5%) and genotype B (3 isolates; 6.25%). When microsatellite technique with primer M13 was applied, 80% of the isolates from the South were placed within the same cluster. All Genotype C strains were grouped together within two different clusters. Genotype C was considered more resistant to PMNs attack than genotypes A and B. Strains isolated from the South of Brazil showed higher ability to combat PMNs phagocytosis. We found a high rate of genotype C strains isolated from the oral cavity of this group of patients. The crude extract of E. uniflora inhibited proper hypha formation and phagocytosis by PMNs, but had no significant effect on phospholipase activity. This study characterized oral C. albicans strains isolated from kidney transplant recipients and will contribute for the better understanding of the pathogenesis and alternative therapeutics for oral candidiasis

Instâncias da representação imagética hiper-real

The approach that undertakes this work revolves around the emergence of iconic structures on reflecting about the meaning of different methods of image representation through which the contemporaneity reveals itself. At baseline, three aspects are considered looking for an analytical ontology of the act of representation and imagery: the transition of representation in the oral culture of societies for writing, from these to typography, and finally the creation of a representation device. Resorted to, therefore, the argument by some genealogy reference points that technological instances such as writing, printing and photography, the evolution of this process, correspond, in itself, a consequent shift technique, for each representation precedent. In the area of the image, the most salient aspect of this change in foward process is the emergence of hyper-reality: the instances of hyper-realistic representation. In the Western context, the 'simulation of the world' - essential idea of mimesis is the work of an autonomous an conventional system. It should be noted, then the fact that under unreflective of the post-industrial societies, the mass-media image is coating with natural or fake code including - according to Baudrillard - tends to replace the real world in the "perpetuation of a large chain of simulacra." Hence in modern times, in the postindustrial society, during the crisis of the representation regimen and perception, centered in the referent. In this limit, new settings are established by aesthetic representations of imagery in contemporary culture: establishing spaces of simulation [Jean Baudrillard] the spectacle [Guy Debord] and hypermodernity [Gilles Lipovetsky] in which they operate. In these assemblages, saps the emergence of Hyper-reality Representation Instances - as seen in this study aesthetic events to configure itineraries of a new sensibility. It is the nature of this practice sign-iconic, ingrained in the creation of current artistic expression, which this research engaged in peering: the hyper-realistic setting, taking empirical support central to contemporary imagery production, diverse formats of analog representation.

A arte rupestre como expressão comunicativa da cultura

Along their existence, through of the millenniuns, the Man registers, one way or another, their saga. One in those registration ways is the rupestrian art. Through the rupestrian art the Prehistory is brought even us, portraying in images the daily ritualist and magic of the Man, in scenes that show, among other, their cults and also their daily hard work. The Man is imposed, while registering of their existence, starting from the moment in that he is capable to leave their marks through the transformation that attributes to the Nature; also for the produced interferences and for the cultural singularities that themselves were constituted before the period of the alphabetical writing. In an artifice of duplicating utensils and in the sense of representing animals and to himself own, he delegated us a communicative system whose contexts and details were - and it continue being - an enigma to be deciphered. Starting from this argument, the research has for objective to understand the daily and the history of cultural groups that they preceded us, taking as base the reading of the rupestrian paintings found at the located archeological ranches in the Area of Seridó, more specifically in the Complexo Xique-xique, close to the Municipal district of Carnaúba dos Dantas, distant 220 kilometers of Natal, the capital of Rio Grande do Norte State

Identidade e participação da comunidade rural nos processos de desenvolvimento local:desafios e competências do regulado de Nhambita-Moçambique

This thesis is defined as a reflection on the mechanisms of expression and insertion of the homo situs in the participatory governance in Mozambique. For a better understanding of this social fact, it was settled a periodization which covered the decline of colonialism at the time of the independence, which was proclaimed in June 1975, the civil war that lasted over 16 years and the period of the democratic State, further established. Therefore, we sought to understand the mechanisms and failures of the participation of the homo situs in local development projects that absorbed the needs and problems of these peasants, not mobilizing the skills and social competences of these communities. It would be essential for the homo situs a genuine democratic practice involving a political culture based on the social construction of the territories of the traditional man which was characterized by being procedural and historical, finding in participation its higher base. In this context, it would be desirable that the community development in Mozambique could contemplate and respect the choices of the homo situs. For this purpose, it would be fundamental the consistency between theory and practice, which builds and rebuilds, continually the competence of the peasants, facilitating the possibility of realization of their primordial aspirations. In the research, it became apparent that there is not a continuous process of participation of the rural communities, which appear as participants, only at the time of the implementation of the activities. Therefore, even having the participation of the communities expected by the law, with predictable moments of discussion and necessary conditions for that, the State failed to establish an ongoing process of democratic dialogue with traditional populations, as well as it failed to organize, properly, accurate informational bases to help solve the problems of rural areas. These facts have led to obstacles to the process of conquest of the human and civil rights of the traditional communities

Trabalho, educação e desenvolvimento: o norte da educação da CUT na Amazônia

This thesis is the result of a bibliographic and field research, with the purpose to answer in what way the process of education developed by the CUT, expressed in the experience of the Project Vento Norte, developed in the Amazônia has colaborated in the sense of the possibility of a articulation between work, education, and develpoment. The bibliographic reasearch was based in the studies of theoreticals like Gadotti (1999), Marx (1998, 1998a), Pochman (2002), Brandão (1985, 2002), Adorno (1999, 2000), Horkeimer (1976), reseachers that in the process of their studies, thinked about the theme, related to work, to education and to developement. The field research was done by the intervews with CUT s educators and managers from the states of Acre, Amazonas, Amapá, Pará, Rondônia and Roraima. The thesis s process of elaboration is done in a cobweb of elements articulated to socioculture values from the habitat of amazônia people. The conclusions point to us that the hypothesis of the CUT, by the Project Vento Norte, develops a propose of education that articulates Work, Education and Development that is confirmed. But, the partiality of the project is presented by the limitations of the CUT s possibility in continuation of the project. Thats why the thesis suports the idea of the project and it consolidation in the Amazônica Region, by the conception of the syndicate managers and educators

Nas asas de Ícaro: uma análise da Pedagogia Freinet do 2º ao 5º ano do Ensino Fundamental na perspectiva da ação docente continuada

Célestin Freinet was one of the most memorable educators of the twentieth century. He presented some educational alternatives that had the objective of stimulating the construction of pedagogic actions to promote the social development of the student based upon a work centered on the free expression as the way to self-structure the knowledge. With a permanent proposal of research based on the enquiry-based learning, Freinet set human capacity (cognitive, social-affective, psychometrical) taking cooperation in consideration on the processes of knowledge construction. Based on this referential, this present work has the objective to show Freinet s pedagogy in a continuous teaching action from 2nd to 5th grade focusing the teacher s discourse and also the educative practice of the students of a city public school in Natal. The observed work revealed the teacher s discourse and educative experience and delineated the students development while immersed into Freinet s educational practice. By virtue of the nature and specificity of the theme that guided our research, we chose a qualitative approach to it, as a way of conducting ourselves during our investigative process. We observed and analyzed the method that was used to conduct the activities in the classroom, as well as the ways of expression that the children used through drawings, words (oral text), or through writing. We highlight, among the written texts, the individual and collective texts, and also letters and notes, which during some moments served as a base to express a diversity of languages. The results, after a analyzing the research data, point towards a teaching practice that favors the construction of a significant learning process through the grasping of the school environment, on which all these factors are based: society, knowledge acquisition, abilities, attitudes and values. This learning process also strengthens human solidarity bonds and mutual tolerance, on which the student s social life is seated.

Já li muita coisa, então, eu posso inventar mais! A leitura literária e o desenvolvimento do pensamento criativo na infância

This study investigates the contributions of reading literature for the development of creative thinking in childhood. Its relevance consists in exploring practices that contemplate the creative thinking development in apprentices at school space and understanding the literature like a significant way to promote the creative thinking. The study is connected to the qualitaty strand. The exploratory observation and the intervention were adopted as research techniques. The field diary and the audio and video recording of the reading sections were adopted as methodological instruments. The research was conducted in the application s college from the Federal University of Rio Grande do Norte, in a 1th grade class, with 18 students between 6 and 7 years old. During the intervention, 8 readind class happened, with varied strategies and literary genres. The reading sessions were conducted through the principles of scaffolding, defended by Graves and Graves (1995). The corpus is made of speaks episodes, whose encoding semantics allowed the grouping into two central categories: divergent thinking and coauthoring of literary reader. It was taken as a theoretical framework the studies of Amarilha (2011; 2006; 2001; 1991; 1993; 1994), Alencar (2001), Coelho (2000; 1997), Culler (1999), De Masi (2005), Gallo (2000), Guilford (1977), Iser (1996), Jouve (2002), Kneller (1978), Martínez (1997), Smith (2003), Stierle (1979), Vigotski (2009; 1998), Wechsler; Nakano (2003; 2002). The analysis points to the formation of creative individuals in the classroom, through the reading of literature. Reposition the literary education front of the new social demands. Resizes the function of school in children s development, considering the children s skill in exploring, testing hypotheses and making use of their creative thinking, in climate of freedom mental. It signals, in this way, the teacher like a mediator, promoting a favorable to the development of creative thinking environment, a stimulating atmosphere, which enhances the expression of creative thinking in community

O desenvolvimento profissional docente e a participação colegiado no Atheneu Norte-Riograndense

To investigate the relationship that exists among the educational participation of the school board and the teacher's professional development, starting from the analysis teachers of a public institution who teaches daily in the city of Natal. We focused the possible relationships between the teacher's action and their professional development, which includes the participation of the School board, considered by us as a collective space. To accomplish this research we used Interviews (KAUFMANN, 1996; SILVA, 2002) to analyze the nine participants, who are teachers' of the school board, and their oral speeches, considered as main references of our study. While trying to understand the reasons that led the teachers to choose her/his educational profession, we noticed the difficulty of recognition of the job of lecturing as a profession. This fact comes as an obstacle to the perspective of the teachers' professional development. In what he/she refers to the forms of the teachers' participation in the board and their meanings, we noticed in first place that the feeling of it belongs one of the decisive factors it can be considered actively for the teacher to announce of the actions colegiadas. This for them to want and they believe that that is the best road for if they develop better while professionals and consequently to improve the situation of the school. In second place we noticed that the school board represents, a place of articulation of the equality among all the ones that form the school community. So, we tried to understand how they happened to the collective actions in the school, how the teachers presented them in spite of what they know, how a collective action should be presented in the elements of fragility of that process that inhibit the development of the overall action. Finally, we questioned the elements that would contribute to the educational professional development; we noticed that the teachers present the competence, the ethics and professional valorization, as factors that contributed at the present time to their educational professional development

Trajetória de vida de mulheres mastectomizadas integrantes de um grupo de auto ajuda a luz da História Oral

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Estudo do Cultivo de dois clones de Escherichia coli recombinantes (eIF, LACK) para a Expressão de Antígenos da Leishmania chagasi

With advent of the technology of the recombinant DNA, the recombinant protein expression becomes an important tool in the studies of the structure, function and identification of new proteins, mainly with therapeutical purposes. The Escherichia coli has been procarioto predominant in the studies of genetic engineering due to wealth of information regarding its metabolism. Despite the expressivo advance of the studies of molecular biology and the immunology of the infections, it does not exist, currently, no prophylactic drug capable to prevent calazar. Of this form, it exists a great necessity of specific antigen identification for the vaccine development and kits for disgnostic against the visceral Leishmaniose. In this context, this work objectified to study the recombinant antigen expression of the Leishmania chagasi during the culture of Escherichia coli in shaker. A first set of assays was carried through with the objective of if knowing the kinetic behavior of the growth of two clones recombinant proteins (eIF, LACK) in two different compositions of culture medium (2xTY, TB) supplemented by antibiotics, without IPTG addition. In the second stage of the assays, the procedure of induction for IPTG was carried through, in order to verify the influence of the composition of the ways tested in the expression them recombinant proteins. On the basis of the gotten results, can be observed that the high complexity of culture medium favored the kinetic one of growth of clones recombinant (eIF, LACK), however, to if to deal with the assays submitted to the procedure of induction for IPTG, the raised complexity of culture medium did not favor the expression of recombinant proteins. On the other hand, they had been gotten resulted positive for all clones recombinant (eIF, LACK) tested, confirmed through the eletroforético profile

Avaliação de dois clones de Escherichia coli recombinante quanto ao crescimento e expressão de antígenos de Leishmania chagasi (kmp11 e P36)

Visceral leishmaniosis caused by Leishmania chagasi, also known as calazar, presented, in the period from 1990 to 2005, tax of incidence in Brazil varying between 1 and 3 cases for 100 000 inhabitants. The Northeast region that up to the year of 2000 contributed with almost 90% of the registered cases is reducing his participation in the current decade, reaching 56% in 2005. Conventional leishmaniasis treatment is costly and it shows high toxicity, demanding more research for alternative treatments, with special interest in development of vaccines and diagnosis kits which include production of recombinant antigens by host cells. Escherichia coli has been the microorganism most studied and used as a host for recombinant protein production. Therefore, the aim of this work was to study the influence of induction on cellular growth and to verify the type of Leishmania chagasi antigens expression (intra or extracellular) during two recombinant E. coli clones (kmp11 and P36) cultivation in rotary incubator (shaker) using three different media (2xTY, TB, FASS+EL). For that, tests were carried out using conditions established in the literature for E. coli (37°C and 200 rpm) and media supplemented with antibiotics to guarantee that only competent cells grows. First, tests were carried out without induction in order to verify the two microorganisms kinetic behavior (growth and substrate consumption) in different media. Next, the induction was carried out through the addition of IPTG (1mM as final concentration), at the first hour of cultivation. It was observed that protein expression were intracellular for all clones and media tested, however the highest level of expression was clearly observed by the electrophoresis band density (intensity) for 2xTY medium and kmp11 protein. Although it contains the lowest substrate concentration, consequently, a reduced cellular concentration when compared to other media, it appeared that this medium and clone combination is the most indicated for recombinant protein production. Therefore, the objective of this work was achieved, since the interested proteins were produced. Consequently, this result motivates new studies for production optimization using different cultivation strategies