Avaliação do potencial de formigas (Hymenoptera: formicidae) como vetores mecânicos de bactérias do gêneroSstaphylococcus no ambiente hospitalar.

In a hospital environment, these bacteria can be spread by insects such as ants, which are characterized by high adaptability to the urban environment. Staphylococcus is a leading cause of hospital infection. In Europe, Latin America, USA and Canada, the group of coagulase negative staphylococci (CoNS) is the second leading cause of these infections, according to SENTRY (antimicrobial surveillance program- EUA). In this study, we investigated the potential of ants (Hymenoptera: Formicidae) as vehicle mechanics of Staphylococcus bacteria in a public hospital, in Natal-RN. The ants were collected, day and night, from June 2007 to may 2008, in the following sectors: hospitals, laundry, kitchen, blood bank. The ants were identified according to the identification key of Bolton, 1997. For the analysis of staphylococci, the ants were incubated in broth Tryptic Soy Broth (TSB) for 24 hours at 35 º C and then incubated on Mannitol Salt Agar. The typical colonies of staphylococci incubated for 24 hours at 35 ° C in Tryptic Soy Agar for the characterization tests (Gram stain, catalase, susceptibility to bacitracin and free coagulase). The identification of CoNS was performed through biochemical tests: susceptibility to novobiocin, growth under anaerobic conditions, presence of urease, the ornithine decarboxylation and acid production from the sugars mannose, maltose, trehalose, mannitol and xylose. The antimicrobial susceptibility examined by disk-diffusion technique. The technique of Polymerase Chain Reaction was used to confirm the presence of mecA gene and the ability to produce biofilm was verified by testing in vitro using polystyrene inert surface, in samples of resistant staphylococci. Among 440 ants, 85 (19.1%) were carrying coagulase-negative staphylococci (CoNS) of the species Staphylococcus saprophyticus (17), Staphylococcus epidermidis (15), Staphylococcus xylosus (13), Staphylococcus hominis hominis (10), Staphylococcus lugdunensis (10), Staphylococcus warneri (6), Staphylococcus cohnii urealyticum (5), Staphylococcus haemolyticus (3), Staphylococcus simulans (3), Staphylococcus cohnii cohnii (2), and Staphylococcus capitis (1). No Staphylococcus aureus was found. Among the isolates, 30.58% showed resistance to erythromycin. Two samples of CoNS (2.35%), obtained from the ant Tapinoma melanocephalum collected in the post-surgical female ward, S. Hominis hominis and S. lugdunensis harbored the mecA gene and were resistant to multiple antibiotics, and the specie S. hominis hominis even showed to be a biofilm producer. This study proves that ants act as carriers of multidrug-resistant coagulase-negative Staphylococci and biofilm producers and points to the risk of the spreading of pathogenic microorganisms by this insect in the hospital environment

Máquina de vetores-suporte intervalar

The Support Vector Machines (SVM) has attracted increasing attention in machine learning area, particularly on classification and patterns recognition. However, in some cases it is not easy to determinate accurately the class which given pattern belongs. This thesis involves the construction of a intervalar pattern classifier using SVM in association with intervalar theory, in order to model the separation of a pattern set between distinct classes with precision, aiming to obtain an optimized separation capable to treat imprecisions contained in the initial data and generated during the computational processing. The SVM is a linear machine. In order to allow it to solve real-world problems (usually nonlinear problems), it is necessary to treat the pattern set, know as input set, transforming from nonlinear nature to linear problem. The kernel machines are responsible to do this mapping. To create the intervalar extension of SVM, both for linear and nonlinear problems, it was necessary define intervalar kernel and the Mercer s theorem (which caracterize a kernel function) to intervalar function

A ocupação urbana do entorno de zonasde proteção ambiental de natal, suas condições de sustentabilidade e a relação com a ocorrência de insetos vetores

This study started from the hypothesis of the existence of a relation between the type of the urban occupation concerning to the sustainability conditions at the proximity of Environment Protected Zones and the occurrence of vectors insects in Natal, Rio Grande do Norte, Brazil. This research, which used data available by the City Administration Health and Urbanization Secretaries (respectively SMS and SEMURB), in the time period of 2006 to 2008, aimed to characterize the study site in terms of urban occupation, relating it to social environmental aspects of land occupation and the occurrence of vectors insects. This study is presented in two papers, the first one linking the occurrence of vectors insects and sustainable development indicators and the second relating the incidence of reported cases of Dengue and Dengue Hemorrhagic Fever (DHF) and the occurrence of larvae infection indexes of Aedes aegypti, in Natal, Rio Grande do Norte State. In the first paper, was made a correlation between Dengue Fever vectors and Visceral and Tegumentar Leishmaniasis vectors and sustainable development indicators, selected from IDS Brasil- 2008. Through factorial analysis a Sustainability Index (SI) was acquired for each region, the northern region of the municipality obtained lower numbers than southern region, which, in its turn, presented better sustainability conditions. Linking this index to vector infestation parameters shows a high significant correlation between the SI and the Breteau Index of Aedes aegypti (p=0,028) as well as with SI and sand flies infestation index (p=0,01). Higher rates in vectors infestation in regions with a lower Sustainable Development Index demonstrates that this index can be used to determine the increasing of probability of Aedes and sand flies occurrence in urban environment. The second paper analyzed the occurrence of the main vector of Dengue and DHF, the Aedes aegypti mosquito, and the relation between larvae infection indexes of this insect and reported cases of the diseases. This study revealed unexpected relation where areas with higher Breteau s Indexes showed lower infection rates of Dengue Fever, although showing high incidence of DHF

Culicídeos vetores em uma unidade de conservação da caatinga na região do seridó no Rio Grande do Norte aspectos da transmissão de doenças

The scarcity of occurrence records of culicid species, transmitting insects of etiologic agents for arboviruses, protozoan diseases and philarioses, and lack of information about their interactions with the forest environment make the Caatinga one of the most unknown biomes in Brazil. The aim of this study was to identify culicid species in a conservation unit located in a preserved area of the Caatinga and the possible associations with local abiotic factors, as well as characterize the natural and artificial ecotopes present in the Caatinga of Rio Grande do Norte state. The Ecological Station of Serido (ESEC-Seridó) is a Caatinga Conservation Unit located in a rural area of Rio Grande do Norte. The hot and dry climate of the Caatinga, along with a short rainy season, favor the adaptation and resistance of plants, resulting in completely distinct landscapes over the course of the year. The study took place over the course of one year, with monthly collections between 10h-12h, 14h-16h and 18h-20h. Adult mosquitoes were collected in a forest area using a manual suction trap with human bait as attractant at the three times and a Shannon trap for night collections. During the rainy season ovitraps were randomly distributed at different sites. The different capture sites were observed and photographed. Immature and adult insects captured were taken to the laboratory for identification. Of the 5081 insects collected in human-bait and Shannon traps, 75% were Mansonia wilsoni. In addition, Aedeomyia, Aedes, Anopheles, Coquillettidia, Culex, Haemagogus, Mansonia and Psorophora were identified. Of the 92 Haemagogus eggs found, 71 were collected on the banks of a reservoir. Mosquito larvae were found and photographed in an artificial breeding site of a neighboring rural area. Humidity had the greatest influence on culicid density in the Caatinga. Rain was important in the appearance of Haemagogus, Anopheles, Aedes and Psorophora. Temperature had a negative influence on Anopheles triannulatus. The occurence of important vector species of diseases in a little known preserved area of the Caatinga as well as environmental and sociocultural questions are factors that favor the emergence of transmitting insects, making these areas potential subject to the resurgence of diseases

Avaliação do potencial de formigas (Hymenoptera: formicidae) como vetores mecânicos de bactérias do gêneroSstaphylococcus no ambiente hospitalar.

In a hospital environment, these bacteria can be spread by insects such as ants, which are characterized by high adaptability to the urban environment. Staphylococcus is a leading cause of hospital infection. In Europe, Latin America, USA and Canada, the group of coagulase negative staphylococci (CoNS) is the second leading cause of these infections, according to SENTRY (antimicrobial surveillance program- EUA). In this study, we investigated the potential of ants (Hymenoptera: Formicidae) as vehicle mechanics of Staphylococcus bacteria in a public hospital, in Natal-RN. The ants were collected, day and night, from June 2007 to may 2008, in the following sectors: hospitals, laundry, kitchen, blood bank. The ants were identified according to the identification key of Bolton, 1997. For the analysis of staphylococci, the ants were incubated in broth Tryptic Soy Broth (TSB) for 24 hours at 35 º C and then incubated on Mannitol Salt Agar. The typical colonies of staphylococci incubated for 24 hours at 35 ° C in Tryptic Soy Agar for the characterization tests (Gram stain, catalase, susceptibility to bacitracin and free coagulase). The identification of CoNS was performed through biochemical tests: susceptibility to novobiocin, growth under anaerobic conditions, presence of urease, the ornithine decarboxylation and acid production from the sugars mannose, maltose, trehalose, mannitol and xylose. The antimicrobial susceptibility examined by disk-diffusion technique. The technique of Polymerase Chain Reaction was used to confirm the presence of mecA gene and the ability to produce biofilm was verified by testing in vitro using polystyrene inert surface, in samples of resistant staphylococci. Among 440 ants, 85 (19.1%) were carrying coagulase-negative staphylococci (CoNS) of the species Staphylococcus saprophyticus (17), Staphylococcus epidermidis (15), Staphylococcus xylosus (13), Staphylococcus hominis hominis (10), Staphylococcus lugdunensis (10), Staphylococcus warneri (6), Staphylococcus cohnii urealyticum (5), Staphylococcus haemolyticus (3), Staphylococcus simulans (3), Staphylococcus cohnii cohnii (2), and Staphylococcus capitis (1). No Staphylococcus aureus was found. Among the isolates, 30.58% showed resistance to erythromycin. Two samples of CoNS (2.35%), obtained from the ant Tapinoma melanocephalum collected in the post-surgical female ward, S. Hominis hominis and S. lugdunensis harbored the mecA gene and were resistant to multiple antibiotics, and the specie S. hominis hominis even showed to be a biofilm producer. This study proves that ants act as carriers of multidrug-resistant coagulase-negative Staphylococci and biofilm producers and points to the risk of the spreading of pathogenic microorganisms by this insect in the hospital environment

A Performance como Outro Lugar da Escrita: Escritura, Autoperformance e Emergência

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Estudo sobre a participação de rodedores na cadeia de transmissão de Leishmania infantum (Protozoa: Trypanosomatidae) no Rio Grande do Norte

American visceral leishmaniasis is a zoonosis caused by Leishmania infantum and transmitted by the bite of the sand flies Lutzomia longipalpis.The main domestic reservoir is the dog, while foxes and opposums are the known wild reservoirs. However, identification of natural infections with L. infantum in rodents appears for need of investigating the participation of these rodents how source of infection of the parasite. In the present work the Leishmania infantum infection was investigated in rodents captured in Rio Grande do Norte, aiming at to offer subsidies to the understanding of the epidemic chains of LVA in the State. Thirteen Galea spixii were distributed in four groups, being G1 the group control with four animals and the others, G2, G3 and G4, with three animals each. Those animals were intraperitoneally inoculated with 107 promastigotas of L. infantum and accompanied for, respectively, 30, 90 and 180 days. Weekly the animals were monitored as for the corporal weight and rectal temperature. At the end of each stipulated period the animals were killed. Blood were used for determination of the parameters biochemical and haematological, PCR, ELISA, microscopic examination and cultivation in NNN medium. Liver, spleen and lymph node were used in Giemsa-stained impression and cultivation in NNN medium. Liver and spleen fragments were still used in PCR and histopathological, respectively. At the same time 79 rodents of the species Rattus rattus, Bolomys lasiurus, Oligoryzomys nigripis, Oryzomys subflavus and Trichomys apereoides were captured in the Municipal districts of Brejinho, Campo Grande, Coronel Ezequiel, Passa e Fica and Vázea for identification of natural infection with L. infantum. Evidence of infection was checked by direct examination of Giemsa-stained impression of liver, spleen and blood and culture of these tissues in NNN medium. Antibodies were researched by ELISA. They were not found differences among the weigh corporal final, rectal temperature and biochemical and haematological parameters of the Galea spixii controls and infected. The rectal temperature of the animals varied from 36OC to 40OC. For the first time values of the haematocrit (33,6% to 42,8%), hemoglobin (10,2 to 14,5g/dl), erythrocyts number (4,67x106 to 6,90x106/mm3), total leukocytes (0,9x103 to 9,2x103/mm3), platelets (49x103 to 509x103/mm3) total proteins (1,56 to 6,06 g/dl), albumin (1,34 to 3,05 g/dl) and globulins (0,20 to 3,01 g/dl) of the Galea spixii were determined. The lymphocytes were the most abundant leucocytes. Infection for L. infantum was diagnosed in two animals euthanasied 180 days after the infection. In one of the animals was also identified antibodies anti-Leishmania. The parasite was not found in none of the five other species of rodents captured. Galea spixii are resistant to the infection for L. infantum and they are not good models for the study for visceral leishmaniose, although they can act as infection sources. More studies are necessary to determine the paper of the rodents in the epidemic chain of transmission of the visceral leishmaniose in the State of Rio Grande do Norte

Desenvolvimento de nanosistemas farmacêuticos para terapia gênica

Gene therapy is one of the major challenges of the post-genomic research and it is based on the transfer of genetic material into a cell, tissue or organ in order to cure or improve the patient s clinical status. In general, gene therapy consists in the insertion of functional genes aiming substitute, complement or inhibit defective genes. The achievement of a foreigner DNA expression into a population of cells requires its transfer to the target. Therefore, a key issue is to create systems, vectors, able to transfer and protect the DNA until it reaches the target. The disadvantages related to the use of viral vectors have encouraged efforts to develop emulsions as non-viral vectors. In fact, they are easy to produce, present suitable stability and enable transfection. The aim of this work was to evaluate two different non-viral vectors, cationic liposomes and nanoemulsions, and the possibility of their use in gene therapy. For the two systems, cationic lipids and helper lipids were used. Nanoemulsions were prepared using sonication method and were composed of Captex® 355; Tween® 80; Spam® 80; cationic lipid, Stearylamine (SA) or 1,2-dioleoyl-3-trimethylammoniumpropane (DOTAP) and water (Milli-Q®). These systems were characterized by average droplet size, Polidispersion Index (PI) and Zeta Potential. The stability of the systems; as well as the DNA compaction capacity; their cytotoxicity and the cytotoxicity of the isolated components; and their transfection capacity; were also evaluated. Liposomes were made by hydration film method and were composed of DOTAP; 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), containing or not Rhodaminephosphatidylethanolamine (PE- Rhodamine) and the conjugate Hyaluronic Acid DOPE (HA-DOPE). These systems were also characterized as nanoemulsions. Stability of the systems and the influence of time, size of plasmid and presence or absence of endotoxin in the formation of lipoplexes were also analyzed. Besides, the ophthalmic biodistribution of PE-Rhodamine containing liposomes was studied after intravitreal injection. The obtained results show that these systems are promising non-viral vector for further utilization in gene therapy and that this field seems to be very important in the clinical practice in this century. However, from the possibility to the practice, there is still a long way

Caracterização batimétrica e fisicooceanográfica do canal de acesso ao porto de Cabedelo/PB: uma análise ambiental ao derrame de óleo

The State of Paraíba is one of the most dynamic states of Brazil, strategically located in the northeast, is notable for the excellent potential for integration of different transportation modes forming the states of Rio Grande do Norte, Pernambuco and Alagoas. The dynamic that occurs with port activity causes changes in the space where it is installed. And the elements of this space are always more than suffering direct or indirect influences as the flow in the port is expanded. Therefore, this region became subject to the accidental spillage of oil, because it presents a heavy traffic of ships of various sizes that can run aground or collide with oil causing accidental events. The study of geomorphological and sedimentological compositions of seafloor becomes important as more is known about the relationships between these parameters and associated fauna, and can identify their preferred habitats. The database background, acoustically collected along the proposed study area, is a wealth of information, which were duly examined, cataloged and made available. Such information can serve as an important tool, providing a geomorphological survey of the sedimentary area studied, and come to subsidize, in a flexible, future decision making. With the study area Port of Cabedelo, Paraíba - Brazil, this research aimed to evaluate the influence of the tidal surface and background in modeling the seabed, including the acquisition of information about the location of submerged rocky bodies and the depth of these bodies may turn out to be natural traps for the trapping of oil in case of leaks, and obtain the relationship between types of bed and the hydrodynamic conditions present in the region. In this context, for this study were collected bathymetric data (depth) and physical oceanographic (height of water column, water temperature, intensity and direction of currents, waves and turbidity), meteorological (rainfall, air temperature, humidity, winds and barometric pressure) of the access channel to the Port of Cabedelo / PB and its basin evolution (where the cruise ships dock), and includes tools of remote sensing (Landsat 7 ETM +, 2001), so that images and the results are integrated into Geographic Information Systems and used in the elaboration of measures aimed at environmental protection areas under the influence of this scale facilities, serving as a grant to prepare a contingency plan in case of oil spills in the region. The main findings highlight the techniques of using hydroacoustic data acquisition together bathymetric surveys of high and low frequency. From there, five were prepared in bathymetric pattern of Directorate of Hydrography and Navigation - DHN, with the depth in meters, on a scale of 1:2500 (Channel and Basin Evolution of Access to Port of Cabedelo), where there is a large extent possible beachrocks that hinder the movement of vessels in the port area, which can cause collisions, running aground and leaking oil. From the scatter diagram of the vectors of currents, it can be seen as the tidal stream and undergoes a channeling effect caused by the bidirectional effect of the tide (ebb and flood) in the basin of the Port of Cabedelo evolution in NW-direction SE and the highest speed of the currents occurs at low tide. The characterization weather for the period from 28/02 to 04/07/2010 values was within the expected average for the region of study. The multidisciplinary integration of products (digital maps and remote sensing images), proved to be efficient for the characterization of underwater geomorphological study area, reaching the aim to discriminate and enhance submerged structures, previously not visible in the images

Potencial larvicida de extratos de plantas regionais no controle de larvas de Aedes aegypti

Dengue, amongst the virus illnesses one can get by vectorial transmission, is the one that causes more impact in the morbidity and mortality of world s population. The resistance to the insecticides has caused difficulties to control of vector insect (Aedes aegypti) and has stimulated a search for vegetables with larvicidal activity. The biodiversity of Caatinga is barely known and it is potential of use even less. Some plants of this biome are commercialized in free fairs northeast of Brazil, because of its phytotherapics properties. The vegetables in this study had been selected by means of a questionnaire applied between grass salesmen and natives of the Serido region from Rio Grande do Norte state; culicids eggs had been acquired with traps and placed in container with water for the larva birth. Thirty larvae had been used in each group (a group control and five experimental groups), with four repetitions four times. The vegetables had been submitted to the processes of decoction, infusion and maceration in the standard concentration of 100g of the vegetable of study in 1l of H2O and analyzed after ½, 1, 2, 4, 8, 12, 24 and 48 hours for verification of the average lethal dose (LD50) from the groups with thirty larva. The LD50 was analyzed in different concentrations (50g/l, 100g/l, 150g/l, 200g/l e 300g/l) of Aspidosperma pyrifolium Mart. 48 extracts of rind, leaf and stem of the seven vegetal species: Aspidosperma pyrifolium Mart., Mimosa verrucosa Benth, Mimosa hostilis (Mart.) Benth., Myracrodruon urundeuva Allemão, Ximenia americana L, Bumelia sartorum Mart Zizyphus joazeiro Mart, had been analyzed. The extracts proceeding from the three methods were submitted to the freezedrying, to evaluate and to quantify substances extracted in each process. The results had shown that Aspidosperma pyrifolium Mart. and Myracrodruon urundeuva Allemão are the species that are more distinguished as larvicidal after 24 hours of experiment, in all used processes of extraction in the assays. The Zizyphus joazeiro Mart species has not shown larvicidal activity in none of the assays. In relation to the extraction method, the decoction was the most efficient method in the mortality tax of the A. aegypti larvae

Ocorrência da infecção por Toxoplasma gondii e avaliação da imunização em caprinos do sertão do cabugi, Rio Grande do Norte

Toxoplasmosis is one zoonosis caused by Toxoplasma gondii protozoan. Goats, amongst the production animals, are one of the species most susceptible to this parasite, being one them main involved agents in ovine and goat abortions, determining great economic losses and implications for public health, since the presence it parasite in the products of goat origin, consist in one of the main sources of infection for the man. In this study 244 blood samples in 8 farms situated in 4 cities from the Sertão do Cabugi region, Rio Grande do Norte State, northeast of Brazil and, tested by ELISA assay. The results had shown a prevalence of 47.13% for anti- T. gondii antibodies and a significant association between positivity and variable evaluated as age, locality and property. The IgG avidity assay evaluated in 115 positive samples was carried to discriminate acute and chronic infection. Twelve samples (10.4%) had presented antibodies of low avidity while 103 (89.6%) presented high avidity antibodies; indicating that most of the animals was precocious exposure to the parasite. Significant difference was verified only for the variable sex. We also evaluate the capacity of recombinant adenoviruses codifying SAG1, SAG2, SAG3 and CMV in inducing activation of specific immune response in goat. These 109 animals received 109 pfu of the AdSAG1, AdSAG2, AdSAG3, AdCMV or PBS in vaccine protocol with 3 immunizations. Serum samples of the each animal, before and after mmunization, had been submitted to the ELISA. The results demonstrate that the immunizations had induced the production of IgG antibodies specific against T. gondii proteins

Proteínas SAG1, SAG2, SAG3 de toxoplasma gondii como perspectivas para o desenvolvimento de protótipo vacinal contra a toxoplasmose

Toxoplasmosis is a zoonosis of worldwide distribution caused by the protozoan Toxoplasma gondii, triggering dangerous complications in immunocompromised patients and pregnant women, as well as having great economic impact for the livestock. So far the control of toxoplasmosis is made primarily by chemotherapy. However, most drugs used routinely have some limitations. In order to control this disease, several research groups, including ours, has been working to develop a medical-veterinary vaccine based on parasite antigens, vectors and protocols of immunization. In this study were implemented and standardized methodologies for amplification and cloning of recombinant immunogens in the system for the development of a prototype vaccine, based on the surface antigens of T. gondii and recombinant adenovirus encoding these antigens. Genes encoding BAG1, GRA2 and SAG1 proteins were amplified. We established a strategy for cloning SAG1, SAG2, SAG3 and TgAMA1- genes in recombinant system. The genes encoding SAG1 and SAG2 were cloned and their sequences showed high similarity with sequences from GenBank. The virtual translation of these proteins showed polymorphisms in the amino acid sequence, which can be correlated with levels of antigenicity. Simultaneously, the adenovirus encoding the SAGs (HAdSAGs) were expanded, purificated and characterizated. Immunization of C57bl/6 mice, using viral supernatant was not enought to elicit immune responses at high levels, being required HAdSAGs titration for future immunizations. Therefore, this study allowed the cloning of the two genes important for the development of a prototype vaccine. Besides, implementations methodologies that permit advancements in the development of a vaccine against toxoplasmosis using adenovirus to express proteins of the parasite

Antígenos da forma amastigota de Leishmania chagasi identificados por dupla varredura da biblioteca de cDNA

Control of human visceral leishmaniasis in endemic regions is hampered in part by the lack of knowledge with respect of the role reservoirs and vector. In addition, there is not yet an understanding of how non-symptomatic subclinical infection might influence the maintenance of infection in a particular locality. Of worrisome is the limited accessibility to medical care in places with emerging drug resistance. There is still no available protective vaccine either for humans or other reservoirs. Leishmania species are protozoa that express multiple antigens which are recognized by the vertebrate immune system. Since there is not one immunodominant epitope recognized by most hosts, strategies must be developed to optimize selection of antigens for prevention and immunodiagnosis. For this reason, we generated a cDNA library from the intracellular amastigote form of Leishmania chagasi, the causative agent of South American visceral leishmaniasis. We employed a two-step expression screen of the library to systematically identify T and T-dependent B cell antigens. The first step was aimed at identifying the largest possible number of clones producing an epitope-containing polypeptide with a pool of sera from Brazilians with documented visceral leishmaniasis. After removal of clones encoding heat shock proteins, positive clones underwent a second step screen for their ability to cause proliferation and IFN-γ responses of T cells from immune mice. Six unique clones were selected from the second screen for further analysis. The clones encoded part of the coding sequence of glutamine synthetase, transitional endoplasmic reticulum ATPase, elongation factor 1γ, kinesin K-39, repetitive protein A2, and a hypothetical conserved protein. Humans naturally infected with L. chagasi mounted both cellular and antibody responses to these protein Preparations containing multiple antigens may be optimal for immunodiagnosis and protective vaccines against Leishmania

Polimorfismos de nucleotídeo único (SNPS) dos genes PPARy2, lipase lipoproteica, receptor de LDL, apolipoproteina C3, e adiponectina podem modular o perfil lipídico de pacientes com a síndrome de Berardinelli-Seip

A Síndrome de Berardinelli-Seip (SBS) é um distúrbio raro do metabolismo dos lipídios, caracterizada pela ausência quase total de tecido adiposo subcutâneo, hipertrigliceridemia, hipoleptinemia e diabetes insulino resistente ou lipoatrófico. Sua etiologia envolve implicações hipotalâmicas, alterações nos receptores de insulina e mutações nos genes AGPAT2, Gng3lg, CAV1 e PTRF. O tecido adiposo secreta diversas substâncias, tais como: leptina, resistina, adiponectina, esteróides, TNF , IL-6, PAI-1, angiotensinogênio, IGF-1. Muitas delas estão associadas ao diabetes mellitus tipo 2, obesidade e hipertensão. Os PPARs são fatores transcricionais pertencentes à superfamília de receptores nucleares ligantes ativados. Sabe-se que o PPAR , é importante para o metabolismo lipídico e glicídico e que o ligante natural do PPAR é derivado do ácido graxo. Nesse sentido, foram avaliados 24 pacientes portadores da SBS, provenientes do Estado do Rio Grande do Norte, com a mediana das idades de 18,5 anos (0,55 a 47 a), sendo 9 (37,5 %) do gênero masculino e 15 (62,5 %) do gênero feminino. Quanto ao grupo étnico, foram classificados em caucasóides (brancos) 21 (87,5 %) e negróides 3 (12,5 %) pacientes. Foram feitas avaliações clínico-endocrinológica, bioquímica, hormonal, molecular e o estudo dos polimorfismos Adiponectina ADIPOQ, PPARγ2 Pro12Ala, LPL-PvuII, APOC3-SstI e LDLR-AvaII em portadores da SBS. Nesta população nós não encontramos nenhuma associação de parâmetros lipídicos e glicídicos com os polimorfismos LPL-PvuII, APOC3-SstI e LDLR-AvaII. Porém, observamos associação entre Adiponectina ADIPOQ e PPARγ2 Pro12Ala e níveis lipídicos mais elevados, sugerindo um papel biológico para estes fatores, indicando estudos mais aprofundados

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