Trabalho político em saúde: a tuberculose no Rio de Janeiro

A intervenção sobre a tuberculose no Rio de Janeiro, Brasil, revela atualmente uma intensificação e alargamento das articulações de pessoas, organizações e instituições envolvidas. Para compreender este processo, recorri ao mapeamento de arenas e mundos sociais. Os mundos sociais definem-se pela partilha de objetivos e de ações, constituindo unidades de ação coletiva. Para atingir os seus objetivos precisam de interagir com outros mundos sociais. Os espaços onde interagem sobre temas de comum interesse, mas sobre os quais têm perspetivas e até objetivos diferentes, denominam-se arenas. O estudo revelou que a arena da tuberculose no Rio de Janeiro se ampliou na última década, aumentando e diversificando os mundos sociais envolvidos, através do “trabalho político” de pessoas e organizações locais, nacionais e internacionais, isto é, através da atribuição de poder a determinadas instâncias com base na valorização ética de objetivos comuns. Este trabalho político tem vindo a implicar a interseção com as arenas do Sistema Único de Saúde e do VIH-Sida. A ampliação da arena da tuberculose redefine a própria doença e as formas de intervir sobre ela. Os apoios socioeconómicos para as/os pacientes, o tratamento de comorbidades, os direitos humanos, bem como outras questões que extravasam a perspetiva biomédica, integram agora as agendas da tuberculose. Neste processo, os intervenientes alargam também as fronteiras da ação na saúde.

QSAR modeling of antitubercular activity of diverse organic compounds

Tuberculosis (TB) is a worldwide infectious disease that has shown over time extremely high mortality levels. The urgent need to develop new antitubercular drugs is due to the increasing rate of appearance of multi-drug resistant strains to the commonly used drugs, and the longer durations of therapy and recovery, particularly in immuno-compromised patients. The major goal of the present study is the exploration of data from different families of compounds through the use of a variety of machine learning techniques so that robust QSAR-based models can be developed to further guide in the quest for new potent anti-TB compounds. Eight QSAR models were built using various types of descriptors (from ADRIANA.Code and Dragon software) with two publicly available structurally diverse data sets, including recent data deposited in PubChem. QSAR methodologies used Random Forests and Associative Neural Networks. Predictions for the external evaluation sets obtained accuracies in the range of 0.76-0.88 (for active/inactive classifications) and Q(2)=0.66-0.89 for regressions. Models developed in this study can be used to estimate the anti-TB activity of drug candidates at early stages of drug development (C) 2011 Elsevier B.V. All rights reserved.

Diagnosis of Tinea pedis and onychomycosis in patients from Portuguese National Institute of Health: a four-year study

ABSTRACT - Tinea pedis and onychomycosis are two rather diverse clinical manifestations of superficial fungal infections, and their etiologic agents may be dermatophytes, non-dermatophyte moulds or yeasts. This study was designed to statistically describe the data obtained as results of analysis conducted during a four year period on the frequency of Tinea pedis and onychomycosis and their etiologic agents. A questionnaire was distributed from 2006 to 2010 and answered by 186 patients, who were subjected to skin and/or nail sampling. Frequencies of the isolated fungal species were cross-linked with the data obtained with the questionnaire, seeking associations and predisposing factors. One hundred and sixty three fungal isolates were obtained, 24.2% of which composed by more than one fungal species. Most studies report the two pathologies as caused primarily by dermatophytes, followed by yeasts and lastly by non-dermatophytic moulds. Our study does not challenge this trend. We found a frequency of 15.6% of infections caused by dermatophytes (with a total of 42 isolates) of which T. rubrum was the most frequent species (41.4%). There was no significant association (p >0.05) among visible injury and the independent variables tested, namely age, gender, owning pet, education, swimming pools attendance, sports activity and clinical information. Unlike other studies, the variables considered did not show the expected influence on dermatomycosis of the lower limbs. It is hence necessary to conduct further studies to specifically identify which variables do in fact influence such infections.

Hydrogen peroxide sensing, signaling and regulation of transcription factors

The regulatory mechanisms by which hydrogen peroxide (H2O2) modulates the activity of transcription factors in bacteria (OxyR and PerR), lower eukaryotes (Yap1, Maf1, Hsf1 and Msn2/4) and mammalian cells (AP-1, NRF2, CREB, HSF1, HIF-1, TP53, NF-κB, NOTCH, SP1 and SCREB-1) are reviewed. The complexity of regulatory networks increases throughout the phylogenetic tree, reaching a high level of complexity in mammalians. Multiple H2O2 sensors and pathways are triggered converging in the regulation of transcription factors at several levels: (1) synthesis of the transcription factor by upregulating transcription or increasing both mRNA stability and translation; (ii) stability of the transcription factor by decreasing its association with the ubiquitin E3 ligase complex or by inhibiting this complex; (iii) cytoplasm-nuclear traffic by exposing/masking nuclear localization signals, or by releasing the transcription factor from partners or from membrane anchors; and, (iv) DNA binding and nuclear transactivation by modulating transcription factor affinity towards DNA, co-activators or repressors, and by targeting specific regions of chromatin to activate individual genes. We also discuss how H2O2 biological specificity results from diverse thiol protein sensors, with different reactivity of their sulfhydryl groups towards H2O2, being activated by different concentrations and times of exposure to H2O2. The specific regulation of local H2O2 concentrations is also crucial and results from H2O2 localized production and removal controlled by signals. Finally, we formulate equations to extract from typical experiments quantitative data concerning H2O2 reactivity with sensor molecules. Rate constants of 140 M-1s−1 and ≥ 1.3 × 103 M-1s−1 were estimated, respectively, for the reaction of H2O2 with KEAP1 and with an unknown target that mediates NRF2 protein synthesis. In conclusion, the multitude of H2O2 targets and mechanisms provides an opportunity for highly specific effects on gene regulation that depend on the cell type and on signals received from the cellular microenvironment.

Cultural organizations and communication in portuguese decentralization policy

This paper intends to show the Portuguese municipalities’ commitment, since the first decade of this century, in cultural facilities of municipal management and how it provided 12 of the 18 district capitals of mainland Portugal with cultural equipment, but after all we want to know if this effort resulted in a regular, diverse, and innovative schedule. Investing in urban regeneration, local governments have tried to convert cities’ demographic changes (strengthening of the most educated and professionally qualified groups) in effective cultural demands that consolidate the three axes of development competitiveness-innovation-creativity. What the empirical study to the programming and communication proposals of those equipment shows is that it is not enough to provide cities with facilities; to escape to a utilitarian conception of culture, there is a whole work to be done so that such equipment be experienced and felt as new public sphere. Equipment in which proposals go through a fluid bind, constructed through space and discourse with local community, devoted a diversified and innovative bet full filling development axis. This paper presents in a systematic way what contributes to this binding on the analyzed equipment.

Cultural organizations and communication in portuguese decentralization policy

This presentation intends to show to what extent the Portuguese municipalities’ commitment, from the first decade of this century, in cultural facilities of municipal management and which has provided 12 of the 18 district capitals of mainland Portugal with equipment, resulted in a regular, diverse and innovative schedule. Investing in urban regeneration, local government has tried to convert cities’ demographic changes (strengthening of the most educated and professionally qualified groups) in effective cultural demands that consolidate the three axes of development competitiveness-innovation-creativity. What the empirical study to the programming and communication proposals of those equipment shows is that it is not enough to provide cities with facilities; to escape to a utilitarian conception of culture, there is a whole work to be done so that such equipment be experienced and felt as new public sphere. Equipment in which proposals go through a fluid bind, constructed through space and discourse with local community, devotes a diversified and innovative bet full filling development axis. This paper presents in a systematic way what contributes to this binding on the analyzed equipment.

Formaldehyde: exposure and genotoxicity assessments and potential health effects

Worldwide formaldehyde is manipulated with diverse usage properties, since industrial purposes to health laboratory objectives, representing the economic importance of this chemical agent. Therefore, many people are exposed to formaldehyde environmentally and/or occupationally. Considering the latter, there was recommended occupational exposure limits based on threshold mechanisms, limit values and indoor guidelines. Formaldehyde is classified by the International Agency for Cancer Research (IARC) as carcinogenic to humans (group 1), since a wide range of epidemiological studies in occupational exposure settings have suggested possible links between the concentration and duration of exposure and elevated risks of nasopharyngeal cancer, and others cancers, and more recently, with leukemia. Although there are different classifications, such as U.S. EPA that classified formaldehyde as a B1 compound, probable human carcinogen under the conditions of unusually high or prolonged exposure, on basis of limited evidence in humans but with sufficient evidence in animals. Formaldehyde genotoxicity is well-known, being a direct-acting genotoxic compound positively associated for almost all genetic endpoints evaluated in bacteria, yeast, fungi, plants, insects, nematodes, and cultured mammalian cells. There are many human biomonitoring studies that associate formaldehyde occupational exposure to genomic instability, and consequently possible health effects. Besides the link with cancer, also other pathologies and symptoms are associated with formaldehyde exposure, namely respiratory disorders such as asthma, and allergic contact dermatitis. Nowadays, there are efforts to reduce formaldehyde exposure, namely indoor. Europe and United States developed more strict regulation regarding formaldehyde emissions from materials containing this agent. Despite the regulations and restrictions, formaldehyde still continues to be difficult to eliminate or substitute, being biomonitoring an important tool to control possible future health effects.

In situ NIR spectroscopy monitoring of plasmid production processes effect of producing strain, medium composition and the cultivation strategy

BACKGROUNDWhile the pharmaceutical industry keeps an eye on plasmid DNA production for new generation gene therapies, real-time monitoring techniques for plasmid bioproduction are as yet unavailable. This work shows the possibility of in situ monitoring of plasmid production in Escherichia coli cultures using a near infrared (NIR) fiber optic probe. RESULTSPartial least squares (PLS) regression models based on the NIR spectra were developed for predicting bioprocess critical variables such as the concentrations of biomass, plasmid, carbon sources (glucose and glycerol) and acetate. In order to achieve robust models able to predict the performance of plasmid production processes, independently of the composition of the cultivation medium, cultivation strategy (batch versus fed-batch) and E. coli strain used, three strategies were adopted, using: (i) E. coliDH5 cultures conducted under different media compositions and culture strategies (batch and fed-batch); (ii) engineered E. coli strains, MG1655endArecApgi and MG1655endArecA, grown on the same medium and culture strategy; (iii) diverse E. coli strains, over batch and fed-batch cultivations and using different media compositions. PLS models showed high accuracy for predicting all variables in the three groups of cultures. CONCLUSIONNIR spectroscopy combined with PLS modeling provides a fast, inexpensive and contamination-free technique to accurately monitoring plasmid bioprocesses in real time, independently of the medium composition, cultivation strategy and the E. coli strain used.