In vitro basal cytotoxicity assay applied to estimate acute oral systemic toxicity of grandisin and its major metabolite

Preclinical investigations can start with preliminary in vitro studies before using animal models. Following this approach, the number of animals used in preclinical acute toxicity testing can be reduced. In this study, we employed an in-house validated in vitro cytotoxicity test based on the Spielmann approach for toxicity evaluation of the lignan grandisin, a candidate anticancer agent, and its major metabolite. the 4-O-demethylgrandisin, by neutral red uptake (NRU) assay, on mouse fibroblasts Balb/c 3T3 cell line. Using different concentrations of grandisin and its major metabolite (2.31; 1.16; 0.58; 0.29; 0.14; 0.07; 0.04; 0.002 mu M) in Balb/c 3T3-A31 NRU cytotoxicity assay, after incubation for 48 h, we obtained IC(50) values for grandisin and its metabolite of 0.078 and 0.043 mu M, respectively. The computed LD(50) of grandisin and 4-O-demethylgrandisin were 617.72 and 429.95 mg/kg, respectively. Both were classified under the Globally Harmonized System as category 4. Since pharmacological and toxicological data are crucial in the developmental stages of drug discovery, using an in vitro assay we demonstrated that grandisin and its metabolite exhibit distinct toxicity profiles. Furthermore, results presented in this work can contribute to reduce the number of animals required in subsequent pharmacological/toxicological studies. (C) 2010 Elsevier GmbH. All rights reserved.

Re-framing risk transfer to assess integrative partnership opportunities: the S.A.R. approach and the AIG/BID/CNO regional surety bond facility of 2007

Identificar, compartilhar e gerenciar os riscos de contratar são preocupações que impedem o estabelicmento e a administração das Parcerias Públicos Particulares (PPP). Porem, gerentes das entidades públicas, bancos de formento, construtoras e seguradoras pesquisam e utilizam muitas técnicas para enfrentar a avaliação e gerenciamento dos riscos. A transferência de risco é uma indicação dos chamados benefícios que são inspirados pelos PPP, contudo devido às realidades contratuais e conceptuais, a entidade de cede o risco (o partido público) permanece quase sempre como o portador final do risco. Conseqüentemente, o partido público retem um interesse de resistência na gerência total destes riscos cedidos. Esta dissertação explora alguns defeitos das aproximações comuns a conceituar a gestão de risco no contexto de um PPP. Focalizando os conceitos da interdependência e da reciprocidade e usando na decisão para transferir o risco do projeto, esta dissertação molda a decisão para transferir o risco nos termos das realidades interdependentes de relacionamentos sistemáticos, alargam os conceitos técnicos do risco e da avaliação de risco, considerando o uso reflexivo das diferenças na analise de um estudo de caso. O autor explora estes conceitos em uma análise da decisão de um gerente de risco da empresa de construção civil brasileira Construtora Norberto Odebrecht (ODB) para projetar uma facilidade inovadora da ligação de garantia com Inter-American Development Bank (BID) e uma seguradora, American International Group (AIG), um negócio que ganhe o reconhecimento Trade Finance Magazine’s 2007 deal of the year. O autor mostra que por compreender a transferência de risco nos termos abordados nesta dissertação, um atore que transfere o risco pode identificar e criar mais oportunidades de estabelecer relacionamentos em longo prazo, através dos processos que a literatura atual do PPP ainda não considere. Os resultados devem fornecer contribuições para a pesquisas sobre a transferência do risco do projeto, na cooperação entre organizações e na seleção do sócio do projeto do potencial.

Análise bioclimática do bairro do Renascença II São Luis-MA: realidade e perspectiva do conforto térmico em espaços externos

The present research concerns about outdoor s thermal comfort conditions in hot-humid climate cities, understanding that life quality is a result of the urban object s type built for the human being in an environment with specific climate and morphological characteristics. It is presented as object of study the correlation between the neighborhood Renascença II s microclimate in São Luis /MA-Brazil, hot-humid climate city, and its urban morphological changes. As well as the thermal comfort s satisfaction level of its outdoor users. The research has as general goal to diagnosis the way these transformations caused by the urbanization influence the Renascença II s microclimate, identifying critical spots of the studied area, in order to contribute with land use recommendations based on bioclimatic architecture concepts and supply bases to urban design decisions adequate to the São Luis climate. It is presented as theoretical bases the urban climate, its concepts and elements. After that, the thermal comfort conditioners and its prediction models of thermal comfort sensation in outdoor are presented. The predictive models are presented along with bioclimatic assessment methods. Finally the use of bioclimatic assessment as an effective tool to identify places that need changes or preservation in order to seek environment quality. The applied methodology was based on the studies of Katzschner (1997), complemented by Oliveira s (1988) and Bustos Romero s (2001) studies that suggest an analysis and evaluation of maps of topography, buildings floors, land use, green areas and land covering, in order to overlap their characteristics and identify climate variable s measurements points; then a quantitative analysis of the climate variables (air temperature and humidity, wind speed and direction) of the chosen points takes place. It was perceived that Renaissance II has no permanence areas as squares or parks, its outdoor has little vegetation and presets high land impermeability and built density levels. The majority of the people interviewed said that was comfortable in a range of air temperature between 27,28ºC and 30,71ºC. The elaboration of a neighborhood master plan is important, which defines strategies for improvement of the life quality of its inhabitants

A simple approach to integrate the ecotoxicological and chemical data for the establishment of environmental risk levels

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

Avaliação de impacto ambiental e gestão dos recursos natuarias no estuário Apodi Mossoró, nordeste do Brasil

The aim of this study is to investigate the eco-environmental vulnerability, its changes, and its causes to develop a management system for application of eco-environmental vulnerability and risk assessment in the Apodi-Mossory estuary, Northeast Brazil. This analysis is focused on the interference of the landscape conditions, and its changes, due to the following factors: the oil and natural gas industry, tropical fruits industry, shrimp farms, marine salt industry, occupation of the sensitive areas; demand for land, vegetation degradation, siltation in rivers, severe flooding, sea level rise (SLR), coastal dynamics, low and flat topography, high ecological value and tourism in the region and the rapid growth of urbanization. Conventional and remote sensing data were analyzed using modeling techniques based on ArcGIS, ER-Mapper, ERDAS Imagine and ENVI software. Digital images were initially processed by Principal Component Analysis and transformation of the maximum fraction of noise, and then all bands were normalized to reduce errors caused by bands of different sizes. They were integrated in a Geographic Information System analysis to detect changes, to generate digital elevation models, geomorphic indices and other variables of the study area. A three band color combination of multispectral bands was used to monitor changes of land and vegetation cover from 1986 to 2009. This task also included the analysis of various secondary data, such as field data, socioeconomic data, environmental data and prospects growth. The main objective of this study was to improve our understanding of eco-environmental vulnerability and risk assessment; it´s causes basically show the intensity, its distribution and human-environment effect on the ecosystem, and identify the high and low sensitive areas and area of inundation due to future SLR, and the loss of land due to coastal erosion in the Apodi-Mossoró estuary in order to establish a strategy for sustainable land use. The developed model includes some basic factors such as geology, geomorphology, soils, land use / land cover, vegetation cover, slope, topography and hydrology. The numerical results indicate that 9.86% of total study area was under very high vulnerability, 29.12% high vulnerability, 52.90% moderate vulnerability and 2.23% were in the category of very low vulnerability. The analysis indicates that 216.1 km² and 362.8 km² area flooded on 1m and 10m in sea levels respectively. The sectors most affected were residential, industrial and recreational areas, agricultural land, and ecosystems of high environmental sensitivity. The results showed that changes in eco-environmental vulnerability have a significant impact on the sustainable development of the RN state, since the indicator is a function of sensitivity, exposure and status in relation to a level of damage. The model were presented as a tool to assist in indexing vulnerability in order to optimize actions and assess the implications of decisions makers and policies regarding the management of coastal and estuarine areas. In this context aspects such as population growth, degradation of vegetation, land use / land cover, amount and type of industrialization, SLR and government policies for environmental protection were considered the main factors that affect the eco-environmental changes over the last three decades in the Apodi-Mossoró estuary.

Assessment of genetic damage induced by dental bleaching agents on mouse lymphoma cells by single cell gel (comet) assay

Dental bleaching is a simple and conservative procedure for aesthetic restoration of vital discoloured teeth. However, dental bleaching agents may represent a hazard to human health, especially by causing DNA strand breaks. Genotoxicity tests form an important part of cancer research and risk assessment of potential carcinogens. In the current study, the genotoxic potential associated with exposure to dental bleaching agents was assessed by the single cell gel (comet) assay in vitro. Six commercial dental bleaching agents (Clarigel Gold - Dentsply; Whitespeed - Discus Dental; Nite White - Discus Dental; Magic Bleaching - Vigodent; Whiteness HP - FGM and Lase Peroxide - DMC) were exposed to mouse lymphoma cells in vitro. The results pointed out that all dental bleaching agents tested contributed to the DNA damage as depicted by the mean tail moment. Clear concentration-related effects were obtained for DNA damaging, being the strongest effect observed at the highest dose of the hydrogen peroxide (Whiteness HP and Lase Peroxide, at 35% concentration). on the contrary, Whitespeed (Discus Dental) induced the lowest level of DNA breakage. Taken together, these results suggest that dental bleaching agents may be a factor that increases the level of DNA damage as detected by the single cell gel (comet) assay.

Mapping soil pollution by spatial analysis and fuzzy classification

Spatial analysis and fuzzy classification techniques were used to estimate the spatial distributions of heavy metals in soil. The work was applied to soils in a coastal region that is characterized by intense urban occupation and large numbers of different industries. Concentrations of heavy metals were determined using geostatistical techniques and classes of risk were defined using fuzzy classification. The resulting prediction mappings identify the locations of high concentrations of Pb, Zn, Ni, and Cu in topsoils of the study area. The maps show that areas of high pollution of Ni and Cu are located at the northeast, where there is a predominance of industrial and agricultural activities; Pb and Zn also occur in high concentrations in the northeast, but the maps also show significant concentrations of Pb and Zn in other areas, mainly in the central and southeastern parts, where there are urban leisure activities and trade centers. Maps were also prepared showing levels of pollution risk. These maps show that (1) Cu presents a large pollution risk in the north-northwest, midwest, and southeast sectors, (2) Pb represents a moderate risk in most areas, (3) Zn generally exhibits low risk, and (4) Ni represents either low risk or no risk in the studied area. This study shows that combining geostatistics with fuzzy theory can provide results that offer insight into risk assessment for environmental pollution.

Increased corticosterone levels in mice subjected to the rat exposure test

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

Pancreatic β-cell defects in women at risk of type 2 diabetes

We evaluated insulin release and insulin sensitivity in women with basal and/or postprandial hyperglycemia but normal oral glucose tolerance test (OGTT) in previous pregnancy (GHG). These women were individually matched with females without previous hyperglycemia (NGT). Both groups consisted of normal glucose-tolerant women at the time of this study. They underwent OGTT (75g; n= 32 pairs) and hyperglycemic clamp experiments (10mmoll-1; n=27 pairs) with plasma glucose, insulin, and C-peptide measurements and calculation of insulinogenic index, first- and second-phase insulin release, and insulin sensitivity index (ISI). The GHG group showed higher glycosylated hemoglobin levels (6.2±0.6% versus 5.8±0.8%; P<0.05); lower insulinogenic index at 30min (134.03±62.69pmolmmol-1 versus 181.59±70.26pmolmmoll-1; P<0.05) and diminished C-peptide response in relation to glucose (4.05±0.36nmolmmol-1 versus 4.23±0.36nmolmmol-1; P<0.05) at OGTT. Both groups did not show difference in insulin secretion and ISI by hyperglycemic clamp technique. We concluded that in up to 12 years from index pregnancy, women with previous GHG, presenting normal glucose tolerance and well-matched with their controls, showed β-cell dysfunction without change in ISI. As women with previous GHG are at risk of type 2 diabetes, β-cell dysfunction may be its primary defect. © 2003 Elsevier B.V. All rights reserved.

Polymorphisms of DNA repair genes XRCC1 and XRCC3, interaction with environmental exposure and risk of chronic gastritis and grastic cancer

Aim: To evaluate the association between polymorphisms XRCC1 Arg194Trp and Arg399Gln and XRCC3 Thr241Met and the risk for chronic gastritis and gastric cancer, in a Southeastern Brazilian population. Methods: Genotyping by PCR-RFLP was carried out on 202 patients with chronic gastritis (CG) and 160 patients with gastric cancer (GC), matched to 202 (C1) and 150 (C2) controls, respectively. Results: No differences were observed among the studied groups with regard to the genotype distribution of XRCC1 codons 194 and 399 and of XRCC3 codon 241. However, the combined analyses of the three variant alleles (194Trp, 399Gln and 241Met) showed an increased risk for chronic gastritis when compared to the GC group. Moreover, an interaction between the polymorphic alleles and demographic and environmental factors was observed in the CG and GC groups. XRCC1 194Trp was associated with smoking in the CG group, while the variant alleles XRCC1 399Gln and XRCC3 241Met were related with gender, smoking, drinking and H pylori infection in the CG and GC groups. Conclusion: Our results showed no evidence of a rela-tionship between the polymorphisms XRCC1 Arg194Trp and Arg399Gln and XRCC3 Thr241Met and the risk of chronic gastritis and gastric cancer in the Brazilian population, but the combined effect of these variants may interact to increase the risk for chronic gastritis, considered a premalignant lesion. Our data also indicate a gene-environment interaction in the susceptibility to chronic gastritis and gastric cancer. © 2005 The WJG Press and Elsevier Inc. All rights reserved.

Chronological Monte Carlo-based assessment of distribution system reliability

Regulatory authorities in many countries, in order to maintain an acceptable balance between appropriate customer service qualities and costs, are introducing a performance-based regulation. These regulations impose penalties, and in some cases rewards, which introduce a component of financial risk to an electric power utility due to the uncertainty associated with preserving a specific level of system reliability. In Brazil, for instance, one of the reliability indices receiving special attention by the utilities is the Maximum Continuous Interruption Duration per customer (MCID). This paper describes a chronological Monte Carlo simulation approach to evaluate probability distributions of reliability indices, including the MCID, and the corresponding penalties. In order to get the desired efficiency, modern computational techniques are used for modeling (UML -Unified Modeling Language) as well as for programming (Object- Oriented Programming). Case studies on a simple distribution network and on real Brazilian distribution systems are presented and discussed. © Copyright KTH 2006.

Effects of motor intervention in elderly patients with dementia: An analysis of randomized controlled trials

The objective of this study was to analyze randomized controlled trials published in the last decades involving motor intervention as a treatment for dementia, based on Physiotherapy Evidence Database (PEDro) criteria. A database search was performed using the following keywords: randomized controlled trial, dementia, physiotherapy, physical therapy, occupational therapy, physical education, motor approach, exercise, and physical activity. Ten trials were found: 4 related to physiotherapy, 3 to occupational therapy, 1 to physical education, and 2 to interdisciplinary motor intervention. The efficacy of motor intervention was confirmed in the following variables: psychosocial function, physical health and function, affective status, and caregiver's distress (P < .05). Results related to mobility were not significant (P > .05). Behavior, cognitive performance, activities of daily living, and risk of falls were not similar among the articles. From a total score of 10 points, with excellence characterized as the highest punctuation, the articles were classified between 3 and 7 by PEDro. Motor intervention was shown to be an alternative for minimizing physical and mental decline. PEDro has been confirmed as a very reliable tool to analyze studies and as an evaluation criteria, both qualitative and quantitative, allowing the establishment of motor intervention strategies for the treatment of patients with dementia. © 2007 Lippincott Williams & Wilkins, Inc.

Influence of lower cutoff values for 100-g oral glucose tolerance test and glycemic profile for identification of pregnant women at excessive fetal growth risk

Objective: To evaluate data from patients with normal oral glucose tolerance test (OGTT) results and a normal or impaired glycemic profile (GP) to determine whether lower cutoff values for the OGTT and GP (alone or combined) could identify pregnant women at risk for excessive fetal growth. Methods: We classified 701 pregnant women with positive screening for gestational diabetes mellitus (GDM) into 2 categories - (1) normal 100-g OGTT and normal GP and (2) normal 100-g OGTT and impaired GP - to evaluate the influence of lower cutoff points in a 100-g OGTT and GP (alone or in combination) for identification of pregnant women at excessive fetal growth risk. The OGTT is considered impaired if 2 or more values are above the normal range, and the GP is impaired if the fasting glucose level or at least 1 postprandial glucose value is above the normal range. To establish the criteria for the OGTT (for fasting and 1, 2, and 3 hours after an oral glucose load, respectively), we considered the mean (75 mg/dL, 120 mg/dL, 113 mg/dL, and 97 mg/dL), mean plus 1 SD (85 mg/dL, 151 mg/dL, 133 mg/dL, and 118 mg/dL), and mean plus 2 SD (95 mg/dL, 182 mg/dL, 153 mg/dL, and 139 mg/dL); and for the GP, we considered the mean and mean plus 1 SD (78 mg/dL and 92 mg/dL for fasting glucose levels and 90 mg/dL and 130 mg/dL for 1- or 2-hour postprandial glucose levels, respectively). Results: Subsequently, the women were reclassified according to the new cutoff points for both tests (OGTT and GP). Consideration of values, in isolation or combination, yielded 6 new diagnostic criteria. Excessive fetal growth was the response variable for analysis of the new cutoff points. Odds ratios and their respective confidence intervals were estimated, as were the sensitivity and specificity related to diagnosis of excessive fetal growth for each criterion. The new cutoff points for the tests, when used independently rather than collectively, did not help to predict excessive fetal growth in the presence of mild hyperglycemia. Conclusion: Decreasing the cutoff point for the 100-g OGTT (for fasting and 1, 2, and 3 hours) to the mean (75 mg/dL, 120 mg/dL, 113 mg/dL, and 97 mg/dL) in association with the GP (mean or mean plus 1 SD-78 mg/dL and 92 mg/dL for the fasting state and 90 mg/dL and 130 mg/dL for 1- or 2-hour postprandial values-increased the sensitivity and specificity, and both criteria had statistically significant predictive power for detection of excessive fetal growth. © 2008 AACE.

Equilíbrio em indivíduos com acidente vascular encefálico: Clínica Escola de Fisioterapia da Uniararas

Objective. To describe balance of stroke patients in the UNIA-RARAS Physical Therapy clinic school evaluating the correlation with age and time of lesion. Method. It was an observational study with 22 subjects, both genders, with diagnosis of stroke, ages ranged from 23 to 86 years old. The subjects were submitted to balance evaluation with Berg's Scale of Functional Balance (BSFB), Brazilian version, composed by fourteen tasks. Results. Stroke patients had an average punctuation of 37 points, showing a high risk of falls. There was no significant correlation between the patient's age and time of lesion with BSFB punctuation. Conclusion. This study showed that stroke patients present high risks of falls, independently of age and time of lesion.