Cholesterol 24S-Hydroxylase overexpression inhibits the liver X receptor (LXR) pathway by activating small guanosine triphosphate-binding proteins (sGTPases) in neuronal cells

The neuronal-specific cholesterol 24S-hydroxylase (CYP46A1) is important for brain cholesterol elimination. Cyp46a1 null mice exhibit severe deficiencies in learning and hippocampal long-term potentiation, suggested to be caused by a decrease in isoprenoid intermediates of the mevalonate pathway. Conversely, transgenic mice overexpressing CYP46A1 show an improved cognitive function. These results raised the question of whether CYP46A1 expression can modulate the activity of proteins that are crucial for neuronal function, namely of isoprenylated small guanosine triphosphate-binding proteins (sGTPases). Our results show that CYP46A1 overexpression in SH-SY5Y neuroblastoma cells and in primary cultures of rat cortical neurons leads to an increase in 3-hydroxy-3-methyl-glutaryl-CoA reductase activity and to an overall increase in membrane levels of RhoA, Rac1, Cdc42 and Rab8. This increase is accompanied by a specific increase in RhoA activation. Interestingly, treatment with lovastatin or a geranylgeranyltransferase-I inhibitor abolished the CYP46A1 effect. The CYP46A1-mediated increase in sGTPases membrane abundance was confirmed in vivo, in membrane fractions obtained from transgenic mice overexpressing this enzyme. Moreover, CYP46A1 overexpression leads to a decrease in the liver X receptor (LXR) transcriptional activity and in the mRNA levels of ATP-binding cassette transporter 1, sub-family A, member 1 and apolipoprotein E. This effect was abolished by inhibition of prenylation or by co-transfection of a RhoA dominant-negative mutant. Our results suggest a novel regulatory axis in neurons; under conditions of membrane cholesterol reduction by increased CYP46A1 expression, neurons increase isoprenoid synthesis and sGTPase prenylation. This leads to a reduction in LXR activity, and consequently to a decrease in the expression of LXR target genes.

Medidas prospectivas de sintomas depressivos entre idosos residentes na comunidade

OBJETIVO: Identificar fatores sociodemográficos associados a padrões de incidência, remissão e estabilidade de sintomas depressivos entre idosos residentes na comunidade. MÉTODOS: Estudo prospectivo em que foram entrevistados 310 idosos residentes na comunidade, em Juiz de Fora, MG, entre 2002 e 2004. O seguimento (T2) foi realizado 15,7 meses após a primeira entrevista (T1). Os sintomas de depressão foram avaliados pela escala do Center for Epidemiological Studies - Depression. Os idosos foram classificados segundo a evolução dos sintomas de depressão e comparados quanto às variáveis sociodemográficas com o teste de qui-quadrado e Exato de Fisher. RESULTADOS: Não houve diferenças na prevalência de sintomas depressivos entre T1 e T2 (33,8%). Foram identificados quatro grupos segundo a evolução dos sintomas da primeira para a segunda medida: livres de depressão (50,9%); recorrência (19,7%); incidência (15,2%); remissão (14,2%). Ter pontuado para depressão em T1, ser do sexo feminino e possuir baixa escolaridade representaram riscos para a manifestação de sintomas depressivos em T2. CONCLUSÕES: Piores trajetórias de evolução em sintomatologia depressiva (incidência e recorrência) associaram-se ao gênero feminino.

Autopercepção da saúde bucal em idosos e fatores associados em Campinas, SP, 2008-2009

OBJETIVO: Descrever a autopercepção de saúde bucal em idosos e analisar fatores sociodemográficos e clínicos associados. MÉTODOS: Estudo transversal com 876 participantes em amostra representativa de idosos (65 anos ou mais) de Campinas, SP, em 2008-2009. Os exames odontológicos seguiram critérios padronizados pela Organização Mundial da Saúde para levantamentos epidemiológicos de saúde bucal. A autopercepção da saúde bucal foi avaliada pelo índice Geriatric Oral Health Assessment Index (GOHAI). Os indivíduos foram classificados segundo características sociodemográficas, odontológicas e prevalência de fragilidade biológica. O estudo de associações utilizou análise de regressão de Poisson; a análise considerou os pesos amostrais e a estrutura complexa da amostra por conglomerados. RESULTADOS: A média de idade dos indivíduos foi de 72,8 anos; 70,1% eram mulheres. A proporção de indivíduos com mais de 20 dentes presentes foi 17,2%; 38,2% usavam prótese dentária total em ambos os arcos; 8,5% necessitavam desse recurso em ao menos um arco dentário. Em média, o índice GOHAI foi elevado: 33,9 (máximo possível 36,0). Manter 20 dentes ou mais, usar prótese total nos dois arcos, não necessitar desse tratamento, não apresentar alterações de mucosa oral e não apresentar fragilidade biológica foram os fatores significantemente associados com melhor autopercepção de saúde bucal (p < 0,05). CONCLUSÕES: A avaliação de autopercepção em saúde bucal permitiu identificar os principais fatores associados a esse desfecho. Esse instrumento pode contribuir para o planejamento de serviços odontológicos, orientando estratégias de promoção em saúde voltadas à melhora da qualidade de vida das pessoas desse grupo etário.

Potential pathogenic fungi assessment through molecular biology in cork industry

Portugal has been the world leader in the cork sector in terms of exports, employing ten thousands of workers. In this working activity, the permanent contact with cork may lead to the exposure to fungi, raising concerns as potential occupational hazards in cork industry. The application of molecular tools is crucial in this setting, since fungal species with faster growth rates may hide other species with clinical relevance, such as species belonging to P. glabrum and A. fumigatus complexes. A study was developed aiming at assessing fungal contamination due to Aspergillus fumigatus complex and Penicillium glabrum complex by molecular methods in three cork industries in the outskirt of Lisbon city.

Fungal burden in waste industry: an occupational risk to be solved

High loads of fungi have been reported in different types of waste management plants. This study intends to assess fungal contamination in one waste-sorting plant before and after cleaning procedures in order to analyze their effectiveness. Air samples of 50 L were collected through an impaction method, while surface samples, taken at the same time, were collected by the swabbing method and subject to further macro- and microscopic observations. In addition, we collected air samples of 250 L using the impinger Coriolis μ air sampler (Bertin Technologies) at 300 L/min airflow rate in order to perform real-time quantitative PCR (qPCR) amplification of genes from specific fungal species, namely Aspergillus fumigatus and Aspergillus flavus complexes, as well as Stachybotrys chartarum species. Fungal quantification in the air ranged from 180 to 5,280 CFU m−3 before cleaning and from 220 to 2,460 CFU m−3 after cleaning procedures. Surfaces presented results that ranged from 29 × 104 to 109 × 104 CFU m−2 before cleaning and from 11 × 104 to 89 × 104 CFU m−2 after cleaning. Statistically significant differences regarding fungal load were not detected between before and after cleaning procedures. Toxigenic strains from A. flavus complex and S. chartarum were not detected by qPCR. Conversely, the A. fumigatus species was successfully detected by qPCR and interestingly it was amplified in two samples where no detection by conventional methods was observed. Overall, these results reveal the inefficacy of the cleaning procedures and that it is important to determine fungal burden in order to carry out risk assessment.

Dimensions of self-rated health in older adults

OBJECTIVE To analyze the association between negative self-rated health and indicators of health, wellbeing and sociodemographic variables in older adults. METHODS Cross-sectional study that used data from a population-based health survey with a probability cluster sample that was carried out in Campinas, SP, Southeastern Brazil,, in 2008 and 2009. The participants were older adults (≥ 60 years) and the dependent variable was self-rated health, categorized as: excellent, very good, good, bad and very bad. The adjusted prevalence ratios were estimated by means of Poisson multiple regression. RESULTS The highest prevalences of bad/very bad self-rated health were observed in the individuals who never attended school, in those with lower level of schooling, with monthly per capita family income lower than one minimum salary. Individuals who scored five or more in the physical health indicator also had bad self-rated health, as well as those who scored five or more in the Self-Reporting Questionnaire 20 and those who did not refer feeling happiness all the time. CONCLUSIONS The independent effects of material life conditions, physical and mental health and subjective wellbeing, observed in self-rated health, suggest that older adults can benefit by health policies supported by a global and integrative view of old age.

Slaughterhouses fungal burden assessment: a contribution for the pursuit of a better assessment strategy

In slaughterhouses, the biological risk is present not only from the direct or indirect contact with animal matter, but also from the exposure to bioaerosols. Fungal contamination was already reported from the floors and walls of slaughterhouses. This study intends to assess fungal contamination by cultural and molecular methods in poultry, swine/bovine and large animal slaughterhouses. Air samples were collected through an impaction method, while surface samples were collected by the swabbing method and subjected to further macro- and micro-scopic observations. In addition, we collected air samples using the impinger method in order to perform real-time quantitative PCR (qPCR) amplification of genes from specific fungal species, namely A. flavus, A. fumigatus and A. ochraceus complexes. Poultry and swine/bovine slaughterhouses presented each two sampling sites that surpass the guideline of 150 CFU/m3. Scopulariopsis candida was the most frequently isolated (59.5%) in poultry slaughterhouse air; Cladosporium sp. (45.7%) in the swine/bovine slaughterhouse; and Penicillium sp. (80.8%) in the large animal slaughterhouse. Molecular tools successfully amplified DNA from the A. fumigatus complex in six sampling sites where the presence of this fungal species was not identified by conventional methods. This study besides suggesting the indicators that are representative of harmful fungal contamination, also indicates a strategy as a protocol to ensure a proper characterization of fungal occupational exposure.

Inquérito preliminar pela reação de Montenegro em população rural no Município de Trajano de Moraes, RJ

Num inquérito pela reação de Montenegro em distrito do município de Trajano de Moraes, RJ, foram testadas 233 pessoas com 12 resultados positivos e 9 duvidosos. Embora a percentagem global (9% somando os positivos e duvidosos) seja bastante baixa, parece haver uma concentração dos resultados positivos em duas localidades (São Francisco de Paula e o Couto), o que poderia sugerir a existência de microfocos numa região onde a doença assume normalmente um caráter eminentemente esporádico.

Comportamento Interpessoal do Professor: um reflexo da sua auto-eficácia?

Dissertação apresentada para cumprimento dos requisitos necessários à obtenção do grau de Mestre em Ciências da Educação

Um caso de leishmaniose cutâneo-mucosa tratado com sucesso com baixa dose de antimonial pentavalente

Os autores relatam um caso de leishmaniose cutâneo-mucosa em uma paciente de 89 anos, diabética e hipertensa, tratada inicialmente com alopurinol por 10 meses não havendo cicatrização das lesões. Posteriormente, recebeu antimoniato de N-metil glucamina (glucantime) por 4 dias, na dose total de 2.380mg do Sb v, mas desenvolveu cardiotoxicidade e hipocalemia, sendo suspenso o tratamento, entretanto, evoluiu com regressão clínica total das lesões, apesar de ter recebido pequena dose desta medicação.

Despopulação neuronal cardíaca em hamsters (Mesocricetus auratus) cronicamente infectados com o Trypanosoma cruzi

Com o objetivo de se obter um modelo experimental que permitisse estabelecer a despopulação (desnervação) neuronal cardíaca procurou-se pesquisar o comportamento do sistema nervoso intracardíaco em hamsters cronicamente infectados com o T. cruzi. Para tal fim, realizaram-se contagens dos neurônios do plexo nervoso autonômico intracardíaco em hamsters inoculados com 35.000 formas sangüíneas de três cepas diferentes, sacrificados 5, 8 e 10 meses depois da infecção. Demonstrou-se, pela primeira vez, destruição neuronal significativa num modelo experimental, similar à que ocorre na doença de Chagas humana.

Lues maligna in an HIV-infected patient

We report such a case of malignant syphilis in a 42-year-old HIV-infected man, co-infected with hepatitis B virus, who presented neurolues and the classical skin lesions of lues maligna. The serum VDRL titer, which was 1:64 at presentation, increased to 1:2,048 three months after successful therapy with penicillin, decreasing 15 months later to 1:8.

Improved polymeric medical devices for active substances delivery

The work presented in this thesis was developed in collaboration with a Portuguese company, BeyonDevices, devoted to pharmaceutical packaging, medical technology and device industry. Specifically, the composition impact and surface modification of two polymeric medical devices from the company were studied: inhalers and vaginal applicators. The polyethylene-based vaginal applicator was modified using supercritical fluid technology to acquire self-cleaning properties and prevent the transport of bacteria and yeasts to vaginal flora. For that, in-situ polymerization of 2-substituted oxazolines was performed within the polyethylene matrix using supercritical carbon dioxide. The cationic ring-opening polymerization process was followed by end-capping with N,N-dimethyldodecylamine. Furthermore, for the same propose, the polyethylene matrix was impregnated with lavender oil in supercritical medium. The obtained materials were characterized physical and morphologically and the antimicrobial activity against bacteria and yeasts was accessed. Materials modified using 2-substituted oxazolines showed an effective killing ability for all the tested microorganisms, while the materials modified with lavender oil did not show antimicrobial activity. Only materials modified with oligo(2-ethyl-2-oxazoline) maintain the activity during the long term stability. Furthermore, the cytotoxicity of the materials was tested, confirming their biocompatibilty. Regarding the inhaler, its surface was modified in order to improve powder flowability and consequently, to reduce powder retention in the inhaler´s nozzle. New dry powder inhalers (DPIs), with different needle’s diameters, were evaluated in terms of internal resistance and uniformity of the emitted dose. It was observed that they present a mean resistance of 0.06 cmH2O0.5/(L/min) and the maximum emitted dose obtained was 68.9% for the inhaler with higher needle´s diameter (2 mm). Thus, this inhaler was used as a test and modified by the coating with a commonly-used force control agent, magnesium stearate, dried with supercritical carbon dioxide (scCO2) and the uniformity of delivered dose tests were repeated. The modified inhaler showed an increase in emitted dose from 68.9% to 71.3% for lactose and from 30.0% to 33.7% for Foradil.

Hiperinfecção por Strongyloides stercoralis: relato de caso autopsiado

Infecção assintomática por Strongyloides stercoralis pode resultar em doença potencialmente fatal em pacientes imunodeprimidos. Os autores relatam caso de hiperinfecção por Strongyloides stercoralis descoberto à autópsia, enfatizando aspectos clinicopatológicos, em homem de 55 anos, em tratamento para mieloma múltiplo. Apresentava, havia um dia, cefaléia intensa, dor abdominal e oligúria desenvolvendo insuficiência respiratória aguda e choque séptico. Devido à dificuldade no diagnóstico, o tratamento empírico antes do início da terapia imunossupressora pode ser a melhor estratégia para prevenir a hiperinfecção pelo verme.

Spatial analysis of visceral leishmaniasis in the municipality of Rondonópolis, in the Brazilian State of Mato Grosso, from 2003 to 2012: human, canine and vector distribution in areas of disease transmission

INTRODUCTION: Visceral leishmaniasis (VL) is a zoonosis of great importance to public health and is considered a neglected disease by the World Health Organization. The disease has expanded and become more prevalent in urban areas in Brazil. METHODS: Geospatial analyses were performed and thematic maps of the triad of the disease were produced for the study period (2003-2012) in the urban area of the municipality of Rondonópolis in the midwestern State of Mato Grosso (MT), Brazil, TerraView 4.2.2 software was used for the analyses. RESULTS: A total of 87.9% of the 186 confirmed human cases of VL were cured. Children between the ages of 1 and 4 were the most affected. Registered deaths were predominant among adults aged 60 years or older. The urban area of the municipality consists of eight strata and 12 census districts include 237 neighborhoods. All sectors had confirmed cases of VL. During the study period, human cases of the disease were recorded in 90 neighborhoods. The 23 deaths from the disease were distributed in 21 neighborhoods. Sandflies carrying the parasite were captured in 192 out of 200 neighborhoods evaluated for the presence of the VL vector. The presence of dogs carrying the parasite was confirmed in, 140 out of 154 surveyed neighborhoods. CONCLUSIONS: The data demonstrated the endemic nature of VL, with a high percentage of infected children, a high distribution of canine infection, and a wide adaptation and dispersal of the vectors in the urban environment. These results, illustrate the process of urbanization of VL in the municipality of Rondonópolis, MT, Brazil.