Obtenção de sistemas multiparticulados de isoniazida revestidos com polímero de liberação entérica

Known for thousands of years, tuberculosis (TB) is the leading cause of mortality by a single infectious disease due to lack of patient adherence to available treatment regimens, the rising of multidrug resistant strains of TB (MDR-TB) and co-infection with HIV virus. Isoniazid and rifampicin are the most powerful bactericidal agents against M. tuberculosis. Because of that, this couple of drugs becomes unanimity in anti-TB treatment around the world. However, the rifampicin in acidic conditions in the stomach can be degraded rapidly, especially in the presence of isoniazid, which reduces the amount of available drug for absorption, as well as its bioavailability, contributing to the growing resistance to tuberculostatic drugs. Rifampicin is well absorbed in the stomach because of its high solubility between pH 1 and 2 and the gastric absorption of isoniazid is considered poor, therefore it is mostly intestinal. This work has as objective the development of gastro-resistant multiple-systems (granules and pellets) of isoniazid aiming to prevent the contact with rifampicin, with consequent degradation in acid stomach and modulate the release of isoniazid in the intestine. Granules of isoniazid were obtained by wet method using both alcoholic and aqueous solutions of PVP K-30 as aggregating and binder agent, at proportions of 5, 8 and 10%. The influence of the excipients (starch, cellulose or filler default) on the physical and technological properties of the granules was investigated. The pellets were produced by extrusionesferonization technique using isoniazid and microcrystalline cellulose MC 101 (at the proportion of 85:15) and aqueous solution of 1% Methocel as platelet. The pellets presented advantages over granular, such as: higher apparent density, smaller difference between apparent and compaction densities, smoother surface and, especially, smaller friability, and then were coated with an organic solution of Acrycoat L 100 ® in a fluidized bed. Different percentages of coating (15, 25 and 50%) were applied to the pellets which had their behavior evaluated in vitro by dissolution in acidic and basic medium. Rifampicin dissolution in the presence of uncoated and coated isoniazid pellets was evaluated too. The results indicate that the gastro resistance was only achieved with the greatest amount of coating and isoniazid is released successfully in basic step. The amount of rifampicin in the dissolution medium when the isoniazid pellets were not coated was lower than in the presence of enteric release pellets. Therefore, the polymer Acrycoat L 100 ® was efficient for coating with gastro-resistant function and can solve the problem of low bioavailability of rifampicin and help to reduce its dosage

Estudo dos fatores associados à infecção chagásica em área endêmica do Rio Grande do Norte

The Chagas disease is a infectious and parasite disease that has as the causative agent a Trypanosoma cruzi, a protozoan parasite that can be transmitted to humans by the faeces of triatomines ( barbeiros ) in the blood-sucking. To understand the relationship between factors associated with chagasic infection and the risk of transmission of Trypanosoma cruzi, this work aimed to make a correlation between the results of serology, obtained by different immunological techniques, used for diagnosis of Chagas disease and risk factors to which the population of the city of Apodi-RN is exposed, to be considered a endemic area. The case-control study was conducted with 199 individuals, which initially was applied a questionary about socio-economic questions and some risk factors which they were exposed and also favor the spread of disease. Then was given the diagnosis by immunological techniques of serology by indirect hemagglutination, ELISA and indirect immunofluorescence. From the diagnosis, the subjects were divided into case group (presence of infection) and control group (no infection). Regarding the descriptive characteristics of the sample, were found a higher frequency of female individuals (59.3%), between 36 and 50 years of age (36.7%), with low education level (91%) and income monthly up to 1 minimum wage (67.8%). The serology, performed by three techniques of different principles, had a reactivity of 38.9% by Indirect Hemagglutination, 39.7% by ELISA and 38.7% by Indirect Immunofluorescence. As the result of the serology, 71 of samples showed reactivity in 2 or more techniques. On some risk variables, was found a significant relationship between individuals who had been bitten by the triatomines and had positive serology for Chagas disease (93.3%). Other variables of risk revealed individuals who had positive serology and had domestic animal (80.3%), lived in poorly maintained homes (97.2%) and near the forest (84.5%). A better understanding of the dynamics of transmission of T. cruzi and the risk factors that contribute to its occurrence in a region are needed to develop effective strategies for control of Chagas disease in these áreas

Infecção por C. psittaci: uma revisão com ênfase em psitacídeos

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Análise de polimorfismos dos genes da rota quinureniana em pacientes com meningite bacteriana.

Bacterial meningitis (BM) is still an important infectious disease causing death and disability. Invasive bacterial infections of the central nervous systems (CNS) generate some of the most powerful inflammatory responses known, which contributes to neuronal damage. The DNA microarray technology showed alterations in the kynurenine (KYN) pathway that is induced in BM and other diseases associated with inflammation, leading to brain injury. Our main aim was to search SNPs previously described in the KYN path enzymes to investigate a putative association of this SNPs with imbalanced in this pathway in patients with BM. The patients included in this study were 33 males and 24 females, with ages varying from 02 months to 68 years. SNPs were located inside of the domain conserved in KYNU, IDO, KATI and KATII. Primers were designed for analysis of SNPs already described by PIRA-PCR followed by RFLP. The analysis of KYNU+715G/A SNP found a heterozygous frequency of 0.033. We did not found the variant allele of SNP KYNU+693G/A, KATI+164T/C, KATII+650C/T and IDO+434T/G. Despite of previews studies showing the importance of KYN pathway we did not found one association of these SNPs analyzed with susceptibility or severity of MB in study population.

Associação entre polimorfismos em enzimas de reparo de DNA e ocorrência de meningite bacteriana.

Despite advances in vaccine development and therapy, bacterial meningitis (BM) remains a major cause of death and long-term neurological disabilities. As part of the host inflammatory response to the invading pathogen, factors such as reactive oxygen species are generated, which may damage DNA and trigger the overactivation of DNA repair mechanisms. It is conceivable that the individual susceptibility and outcome of BM may be in part determined by non synonymous polymorphisms that may alter the function of crucial BER DNA repair enzymes as PARP-1, OGG-1 and APE-1. These enzymes, in addition to their important DNA repair function, also perform role of inflammatory regulators. In this work was investigated the non synonymous SNPs APE-1 Asn148Glu, OGG-1 Ser326Cys,PARP-1 Val762Ala, PARP-1 Pro882Leu and PARP-1 Cys908Tyr in patients with bacterial meningitis (BM), chronic meningitis (CM), aseptic meningitis (AM) and not infected (controls). As results we found increased frequency of variant alleles of PARP-1 Val762Ala (P = 0.005) and APE-1 Asn148Glu (P=0.018) in BM patients, APE-1 Asn148Glu in AM patients (P = 0.012) and decrease in the frequency of the variant allele OGG-1 Ser326Cys in patients with CM (P = 0.013), regarding the allelic frequencies in the controls. A major incidence of individuals heterozygous and/ or polymorphic homozygous in BM for PARP-1 Val762Ala (P= 0.0399, OD 4.2, 95% IC 1.213 -14.545) and PARP-1 Val762Ala/ APE-1 Asn148Glu (P = 0.0238, OD 11.111, 95% IC 1.274 - 96.914) was observed related to what was expected in a not infected population. It was also observed a major incidence of combined SNPs in the BM patients compared with the control group (P=0.0281), giving evidences that SNPs can cause some susceptibility to the disease. This combined effect of SNPs seems to regulate the principal cytokines and other factors related to BM inflammatory response and point the importance of DNA repair not only to repair activity when DNA is damaged, but to others essential functions to human organism balance.

Estudo teórico-bioclimático da potencialidade de desenvolvimento do Aedes aegypti no estado do Rio Grande do Norte

In the current climate of global public health there is the emergence of urban dengue, a disease regarded as acute infectious fever. The disease annually, has affected millions of people worldwide, mostly in the range of the intertropical globe. The disease's main vector in urban areas, the Aedes aegypti mosquito. Recent studies indicate that the distribution of the insect vector of dengue in the geographical area is directly tied to the behavior of environmental restrictions that area, especially among those, the air temperature and relative humidity. From that context, the work aims to estimate and spatializing, monthly, for each municipality in the state of Rio Grande do Norte, the potential of biophysical conditions conducive to the development of Aedes aegypti. Yet, made use of the following methodology: collection of epidemiological data and climatological, Normal climatological, descriptive statistics (measures of central tendency and scatter), uniform distribution, estimation geostatistics and sufer program, version 8.0. The results flagged for a behavior very heterogeneous, both in space and in time, in the case of the potential of biophysical conditions conducive to the development of Aedes aegypti in the state of Rio Grande do Norte. Still, he noted that there is a tendency for lifting the potential of development for the entire state, from the month of January, ending in the month of April mainly in central and western portions of the state. By contrast, there is the permanence of increased potential for development in the eastern portion of the state. The latter record maximum potential in the month of July, resulting probability of greater than 70% have been favorable conditions for the development of Aedes aegypti in that area. In the period between the months of August to December, it is small potential for development of Aedes aegypti in all parts of the state

Borreliose de Lyme

As borrelioses constituem um grupo de doenças infecciosas causadas por espiroquetas do gênero Borrelia. A borreliose de Lyme, também denominada doença de Lyme, é uma doença infecciosa, não contagiosa, causada por espiroquetas pertencentes ao complexo Borrelia burgdorferi Sensu Lato e transmitida, mais frequentemente, por picada de carrapatos do gênero Ixodes. A doença apresenta quadro clínico variado, podendo desencadear manifestações cutâneas, articulares, neurológicas e cardíacas.

A etiologia da cara inchada, uma periodontite epizoótica dos bovinos

Uma versão condensada em português de um artigo de revisão sobre a periodontite da cara inchada dos bovinos, publicado em inglês, está apresentada com algumas informações adicionais. A doença foi responsável por grandes perdas de bovinos jovens, principalmente nas décadas de 1970 e l980 no Brazil Central. em face da periodontite progressiva e a perdas de dentes, os animais não podem se alimentar convenientemente, tornam-se emaciados e podem morrer. A doença foi tida como uma deficiência ou desequilíbrio mineral. Mas as pesquisas de campo e de laboratório, realizadas durante 30 anos, mostraram que trata-se de doença infecciosa multifatorial a ser definida como Periodontite Epizoótica Bovina. Chegou-se à conclusão que os fatores principais para o seu desenvolvimento são: (1) a idade dos bovinos na fase de erupção dos dentes premolares e molares; (2) a presença de bactérias do grupo Bacteroides spp nos espaços subgengivais; e (3) a ingestão com a forragem de concentrações subinibitórias de antibióticos, sobretudo de estreptomicina, produzidos por actinomicetos cujo número é aumentado em solos virgens recém-cultivados na formação de pastagens após a derrubada da mata ou da vegetação de Cerrado; isto leva a um aumento da aderência dos bacteróides ao epitélio gengival e à destruição dos tecidos peridentários. Hoje em dia, a doença perdeu a sua importância e praticamente desapareceu, porque a microbiota do solo entrou novamente em equilíbrio e a abertura de grandes áreas virgens para a pecuária cessou. Porém, novos surtos podem ocorrer em áreas anteriormente positivas para a doença quando, na reforma de pastagens ou capineiras, houver um novo desequilíbrio da microbiota do solo. Outros antibióticos, como a espiramicina e virginiamicina, administrados por via oral ou adicionado a misturas minerais, podem controlar a periodontite.

IgA anti-Streptococcus mutans em crianças com e sem cárie dentária

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Tuberculose e o estudo molecular da sua epidemiologia

Systems that can distinguish epidemiologically-related Mycobacterium tuberculosis strains from unrelated ones are extremely valuable. Molecular biology techniques have allowed a great deal of information to be acquired about the infectious disease tuberculosis (TB) that was very hard or impossible to obtain by conventional epidemiology. A typing method based on bacterial DNA genome differences, known as RFLP (restriction fragment length polymorphism), is widely used to discriminate strains in the epidemiologic study of TB. However, RFLP is laborious and there is a tendency to replace it by other methods. Thus, other DNA sequences have been employed as epidemiological markers, as in Spoligotyping, a fast technique based on PCR followed by differential hybridization of amplified products. The polymorphism observed among different isolates is probably the product of strain-dependent recombination. MIRU (mycobacterial interspersed repetitive unit) typing is a reproducible and fast assay, involving the generation of genotypes based on the study of 12 loci containing VNTRs (variable-number tandem repeats) in strains of the M. tuberculosis complex. It compares strains from different geographic areas and allows the movement of individual lineages to be tracked, as in RFLP. This approach enables a greater number of isolates to be analyzed, leading to the identification of a larger number of foci of transmission within the population and thus to improved ways of slowing the progress of the disease.

Uma abordagem probabilística do número de reprodução básica em modelos epidemiológicos com aplicação na ferrugem do eucalipto

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Uso da pesagem e da paquimetria na monitoração da ileíte suína em abatedouros

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Efeito de desnutrição e das citocinas pró-inflamatórias na infecção experimental em camundongos Balb/c infectados com Trypanosoma cruzi

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Atividade anti - Mycobacterium tuberculosis intra e extra celular e citotoxicidade dos complexos de coordenação de metais

Pós-graduação em Biociências e Biotecnologia Aplicadas à Farmácia - FCFAR

Deteccão de diferentes microorganismos na periodontite crônica, da glicoproteína EMMPRIN (CD-147) e sua correlação com a produção de MMP-2 e MMP-9

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)