Cytotoxic iron chelators: Characterization of the structure, solution chemistry and redox activity of ligands and iron complexes of the di-2-pyridyl ketone isonicotinoyl hydrazone (HPKIH) analogues

Di-2-pyridyl ketone isonicotinoyl hydrazone (HPKIH) and a range of its analogues comprise a series of monobasic acids that are capable of binding iron (Fe) as tridentate (N,N,O) ligands. Recently, we have shown that these chelators are highly cytotoxic, but show selective activity against cancer cells. Particularly interesting was the fact that cytotoxicity of the HPKIH analogues is maintained even after complexation with Fe. To understand the potent anti-tumor activity of these compounds, we have fully characterized their chemical properties. This included examination of the solution chemistry and X-ray crystal structures of both the ligands and Fe complexes from this class and the ability of these complexes to mediate redox reactions. Potentiometric titrations demonstrated that all chelators are present predominantly in their charge-neutral form at physiological pH (7.4), allowing access across biological membranes. Keto-enol tautomerism of the ligands was identified, with the tautomers exhibiting distinctly different protonation constants. Interestingly, the chelators form low-spin (diamagnetic) divalent Fe complexes in solution. The chelators form distorted octahedral complexes with Fe-II, with two tridentate ligands arranged in a meridional fashion. Electrochemistry of the Fe complexes in both aqueous and non-aqueous solutions revealed that the complexes are oxidized to their ferric form at relatively high potentials, but this oxidation is coupled to a rapid reaction with water to form a hydrated (carbinolamine) derivative, leading to irreversible electrochemistry. The Fe complexes of the HPKIH analogues caused marked DNA degradation in the presence of hydrogen peroxide. This observation confirms that Fe complexes from the HPKIH series mediate Fenton chemistry and do not repel DNA. Collectively, studies on the solution chemistry and structure of these HPKIH analogues indicate that they can bind cellular Fe and enhance its redox activity, resulting in oxidative damage to vital biomolecules.

Variation of the crystalline structure of coal char during gasification

The variation of the crystallite structure of several coal chars during gasification in air and carbon dioxide was studied by high-resolution transmission electron microscopy (HRTEM) and X-ray diffraction (XRD) techniques. The XRD analysis of the partially gasified coal chars, based on two approaches, Scherrer's equation and Alexander and Sommer's method, shows a contradictory trend of the variation of the crystallite height with carbon conversion, despite giving a similar trend for the crystallite width change. The HRTEM fringe images of the partially gasified coal chars indicate that large and highly ordered crystallites exist at conversion levels as high as 86%. It is also demonstrated that the crystalline structure of chars can be very different although their pore structures are similar, suggesting a combination of crystalline structure analysis with pore structure analysis in studies of carbon gasification.

The synthesis and X-ray crystal structure of 6-bromo-2,4,4-trimethyl-cyclohex-2-enone

Regiospecific bromination of 2,4,4-trimethyl-cyclohex-2-enone was achieved and the X-ray crystal structure of 6-bromo-2,4,4-trimethyl-cyclohex-2-enone is presented.

The synthesis and X-ray crystal structure of 9-carboxyhexahydro-7-methoxy-4a,7-ethano-benzopyran-5-en-1-one

9-Carboxyhexahydro-7-methoxy-4a,7-ethano-benzopyran-5-en-1-one (1) was prepared and examined by X-ray crystallography to probe its potential as a new peptide scaffold/template. The crystal structure of the anhydride precursor 7-(2-acetoxyethyl)-4-methoxy-3a,4,7,7a-tetrahydro-4,7-ethanoisobenzofuran-1,3-dione (6) is also reported.

Variation of the pore structure of coal chars during gasification

The variation of the pore structure of several coal chars during gasification in air and carbon dioxide was studied by argon adsorption at 87 K and CO2 adsorption at 273 K. It is found that the surface area and volume of the small pores (10 Å for air gasification is constant over a wide range of conversion (>20%), while for CO2 gasification similar results are obtained using the total surface area. However, in the early stages of gasification (

Indicadores para diagn??stico, monitoramento e avalia????o de programas sociais no Brasil

O objetivo do texto ?? discutir as potencialidades e limita????es do uso das informa????es estat??sticas produzidas pelo IBGE e os registros administrativos de ??rg??os p??blicos para a constru????o de indicadores para diagn??stico, monitoramento e avalia????o de programas sociais no Brasil. Inicia-se com uma apresenta????o sobre os aspectos conceituais b??sicos acerca dos indicadores sociais, suas propriedades e formas de classifica????o. Depois, discute-se uma proposta de estrutura????o de um sistema de indicadores para subsidiar o processo de formula????o e avalia????o de pol??ticas e programas p??blicos no Pa??s. Conclui-se o texto advogando-se a necessidade de estruturar sistemas de indicadores que se ap??iem na busca de informa????es j?? existentes em fontes secund??rias e na produ????o de dados no ??mbito dos pr??prios programas.

Structure formation in an expanding universe : I José Plínio Baptista School of Cosmology

José Plínio Baptista School of Cosmology (1. : 2012 : Anchieta, ES). Seminário realizado no período de 14 a 19 de outubro de 2012.

Percepção dos agentes comunitários de saúde frente ao risco de infecção da tuberculose

A Tuberculose é um serio problema de saúde, os níveis mundiais no ano 2011 ocorreram 8,7 milhões de casos novos e 1,4 milhões de pessoas morreram de TB. Para horizontalizar as ações no combate da TB na atenção primaria o Agente Comunitário de Saúde assume um papel muito importante, pois eles além de trabalhar na comunidade onde mora ele é um mediador de saberes, espera-se que esse profissional seja capaz de identificar por meio de visitas domiciliares sintomáticos respiratórios. Objetivos: Conhecer a percepção que os ACS têm sobre o risco de infecção à tuberculose no cotidiano de sua prática profissional e analisar como eles se organizam e estruturam sua prática frente a essa percepção. Abordagem Metodológica: O estudo foi dividido em duas fases a primeira responde ao primer objetivo e foi escolhido o Grupo Focal e para a segunda fase que responde ao segundo objetivo foi escolhido a Observação Participante como técnicas de trabalho em campo e Analise de Conteúdo Temático como técnica de análise das informações colhidas que consiste em descobrir os núcleos de sentidos que são temas os quais são unidades de significação que se libertam naturalmente de um texto analisado. Resultados: Na primeira fase do estudo observou-se que o Agente Comunitário de Saúde percebe os riscos que estão expostos, mas muitas vezes eles não sabem como agir em situações, especificas, na segunda fase indicam que o risco não esta presente o tempo todo na vida e no trabalho deles. Conclusão: O PACS é apresentado pelo Ministério da Saúde como uma estratégia de saúde para horizontalizar as ações no controle da TB, neste estudo foi encontrado que o ACS percebe o risco que esta exposto, mas que aquele risco não esta sempre presenta na vida deles, pois eles muitas vezes minimizam os riscos pensando que nada acontece nem acontecera com eles.

Mechanical Behavior of the Lamellar Structure in Semi-Crystalline Polymers

We have employed molecular dynamics simulations to study the behavior of virtual polymeric materials under an applied uniaxial tensile load. Through computer simulations, one can obtain experimentally inaccessible information about phenomena taking place at the molecular and microscopic levels. Not only can the global material response be monitored and characterized along time, but the response of macromolecular chains can be followed independently if desired. The computer-generated materials were created by emulating the step-wise polymerization, resulting in self-avoiding chains in 3D with controlled degree of orientation along a certain axis. These materials represent a simplified model of the lamellar structure of semi-crystalline polymers,being comprised of an amorphous region surrounded by two crystalline lamellar regions. For the simulations, a series of materials were created, varying i) the lamella thickness, ii) the amorphous region thickness, iii) the preferential chain orientation, and iv) the degree of packing of the amorphous region. Simulation results indicate that the lamella thickness has the strongest influence on the mechanical properties of the lamella-amorphous structure, which is in agreement with experimental data. The other morphological parameters also affect the mechanical response, but to a smaller degree. This research follows previous simulation work on the crack formation and propagation phenomena, deformation mechanisms at the nanoscale, and the influence of the loading conditions on the material response. Computer simulations can improve the fundamental understanding about the phenomena responsible for the behavior of polymeric materials, and will eventually lead to the design of knowledge-based materials with improved properties.

Absorption of primary macronutrients and soybean growth at different compactation densities and moisture levels in a silt loam soil

ABSTRACT Soybean cultivation is increasing rapidly in the region of Alto Vale do Itajaí, State of Santa Catarina, where there is a predominance of silt soils. The objective of this work was to evaluate the content of primary macronutrients in shoots and shoot and root vegetative growth of soybean (Glicine max L. Merrill) grown in a silt-loam soil under different compactation densities and moisture levels. A randomized block design in a 4x4 factorial arrangement was used, with four compactation densities: 1.00; 1.20; 1.40 and 1.60 Mg m-3, and four soil moisture levels: 0.130; 0.160; 0.190 and 0.220 kg kg-1 and four replications. Each pot consisted of the overlapping of three 150-mm PVC rings, where soil was maintained in the higher and lower part of the pot with a density of 1.00 Mg m-3 and in the intermediate ring, the compactation densities were increased. Values of soil density higher than 120 Mg m-3 negatively affected N, P and K uptake by soybean plants, as well as the plant mass of the shoots and roots. The higher levels of soil moisture reduced the compaction effect and promoted better absorption of P and K.

The structure of domination today: a lacanian view

Na era da sensibilidade extrema em relação ao assédio do Outro é cada vez mais comum submeter à crítica, injunções éticas, que nos aterrorizam com a sua imposição brutal do universal. Lacan explica esta violência ética através da passagem do discurso do Amo para o discurso da Universidade enquanto discurso hegemónico da sociedade contemporânea.

Detection of psychiatric morbidity in the primary medical care setting in Brazil

The aims of this study were a) to assess the ability of primary care doctors to make accurate ratings of psychiatric disturbance and b) to evaluate the use of a case-finding questionnaire in the detection of psychiatric morbidity. The estudy took place in three primary care clinics in the city of São Paulo, Brazil, during a six-month survey. A time sample of consecutive adult attenders were asked to complete a case-finding questionnaire for psychiatric disorders (the Self Report Questionnaire - SRQ) and a subsample were selected for a semi-structured psychiatric interview (the Clinical Interview Schedule - CIS). At the end of the consultation the primary care doctors were asked to assess, in a standardized way, the presence or absence of psychiatric disorder; these assessments were then compared with that ratings obtained in the psychiatric interview. A considerable proportion of minor psychiatric morbidity remained undetected by the three primary care doctors: the hidden morbidity ranged from 22% to 79%. When these were compared to those of the case-finding questionnaire, they were consistently lower, indicating that the use of these instruments can enhance the recognition of psychiatric disorders in primary care settings. Four strategies for adopting the questionnaire are described, and some of the clinical consequences of its use are discussed.

Metodological issues in measuring the detection of emotional disorders by primary care physicians: a review of the literature

A series of studies in the field of Epidemiological Psychiatry have been performed over the last two decades, and these have focused on the ability of primary care physicians to detect emotional disorders in the patients that attend their practices. The scientific methodology utilized in these studies is the subject of this review, which contains a discussion concerning: a) interviewer awareness bias; b) accuracy of the instruments and c) medical and psychological concepts involved in defining minor emotional disorders. Suggestions for change in the methodology are made in each of the sections of the review.