Effect of oxidative stress upon absorption of glucose by the human placenta: in vitro studies with BeWo cells

Pregnancy is a dynamic state and the placenta is a temporary organ that, among other important functions, plays a crucial role in the transport of nutrients and metabolites between the mother and the fetus, which is essential for a successful pregnancy. Among these nutrients, glucose is considered a primary source of energy and, therefore, fundamental to insure proper fetus development. Several studies have shown that glucose uptake is dependent on several morphological and biochemical placental conditions. Oxidative stress results from the unbalance between reactive oxygen species (ROS) and antioxidants, in favor of the first. During pregnancy, ROS, and therefore oxidative stress, increase, due to increased tissue oxygenation. Moreover, the relation between ROS and some pathological conditions during pregnancy has been well established. For these reasons, it becomes essential to understand if oxidative stress can compromise the uptake of glucose by the placenta. To make this study possible, a trophoblastic cell line, the BeWo cell line, was used. Experiments regarding glucose uptake, either under normal or oxidative stress conditions, were conducted using tert-butylhydroperoxide (tBOOH) as an oxidative stress inducer, and 3H-2-deoxy-D-glucose (3H-DG) as a glucose analogue. Afterwards, studies regarding the involvement of glucose facilitative transporters (GLUT) and the phosphatidylinositol 3-kinases (PI3K) and protein kinase C (PKC) pathways were conducted, also under normal and oxidative stress conditions. A few antioxidants, endogenous and from diet, were also tested in order to study their possible reversible effect of the oxidative effect of tBOOH upon apical 3H-DG uptake. Finally, transepithelial studies gave interesting insights regarding the apical-to-basolateral transport of 3H-DG. Results showed that 3H-DG uptake, in BeWo cells, is roughly 50% GLUT-mediated and that tBOOH (100 μM; 24h) decreases apical 3H-DG uptake in BeWo cells by about 33%, by reducing both GLUT- (by 28%) and non-GLUT-mediated (by 40%) 3H-DG uptake. Uptake of 3H-DG and the effect of tBOOH upon 3H-DG uptake are not dependent on PKC and PI3K. Moreover, the effect of tBOOH is not associated with a reduction in GLUT1 mRNA levels. Resveratrol, quercetin and epigallocatechin-3-gallate, at 50 μM, reversed, by at least 45%, the effect of tBOOH upon 3H-DG uptake. Transwell studies show that the apical-to-basolateral transepithelial transport of 3H-DG is increased by tBOOH.In conclusion, our results show that tBOOH caused a marked decrease in both GLUT and non-GLUT-mediated apical uptake of 3H-DG by BeWo cells. Given the association of increased oxidative stress levels with several important pregnancy pathologies, and the important role of glucose for fetal development, the results of this study appear very interesting.

Bat rabies in the north-northwestern regions of the state of São Paulo, Brazil: 1997-2002

OBJECTIVE: Reports on bat rabies in Brazil are sporadic and isolated. This study aimed at describing the detection of rabies virus in bats in the state of São Paulo. METHODS: A total of 7,393 bats from 235 municipalities of the north and northwestern areas of the state of São Paulo, Southeastern Brazil, were assessed according to their morphological and morphometric characteristics from 1997 to 2002. Fluorescent antibody test and mice inoculation were used for viral identification. RESULTS: Of all samples examined, 1.3% was rabies virus positive, ranging from 0.2% in 1997 to 1.6% in 2001. There were found 98 bats infected, 87 in the urban area. Fluorescent antibody test was detected in 77 positive samples, whereas 92 produced rabies signs in mice; incubation period ranging from 4 to 23 days. In 43 cities at least one rabid bat was observed. The highest proportion (33.7%) of rabies virus was found in Artibeus lituratus. Eptesicus and Myotis were the most frequent positive species (24.5%) of the Vespertilionidae family. The species Molossus molossus and Molossus rufus showed 14.3% positive bats. There were no differences in the distribution of positive rabies between females (33; 48.5%) and males (35; 51.5%). CONCLUSIONS: Rabies-infected bats were found in environments that pose a risk to both human and domestic animal population and there is a need for actions aiming at the control of these species and public education.

Cellular polarity in aging: role of redox regulation and nutrition

Cellular polarity concerns the spatial asymmetric organization of cellular components and structures. Such organization is important not only for biological behavior at the individual cell level, but also for the 3D organization of tissues and organs in living organisms. Processes like cell migration and motility, asymmetric inheritance, and spatial organization of daughter cells in tissues are all dependent of cell polarity. Many of these processes are compromised during aging and cellular senescence. For example, permeability epithelium barriers are leakier during aging; elderly people have impaired vascular function and increased frequency of cancer, and asymmetrical inheritance is compromised in senescent cells, including stem cells. Here, we review the cellular regulation of polarity, as well as the signaling mechanisms and respective redox regulation of the pathways involved in defining cellular polarity. Emphasis will be put on the role of cytoskeleton and the AMP-activated protein kinase pathway. We also discuss how nutrients can affect polarity-dependent processes, both by direct exposure of the gastrointestinal epithelium to nutrients and by indirect effects elicited by the metabolism of nutrients, such as activation of antioxidant response and phase-II detoxification enzymes through the transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2). In summary, cellular polarity emerges as a key process whose redox deregulation is hypothesized to have a central role in aging and cellular senescence.

Controlo clássico vs. preditivo na regulação de frequência em sistemas de potência

Dissertação para obtenção do grau de Mestre em Engenharia Electrotécnica Ramo Automação e Electrónica Industrial

Factors related to inadequate cervical cancer screening in two Brazilian state capitals

OBJECTIVE:To analyze factors associated with cervical cancer screening failure. METHODS:Population-based cross-sectional study with self-weighted two-stage cluster sampling conducted in the cities of Fortaleza (Northeastern Brazil) and Rio de Janeiro (Southeastern Brazil) in 2002. Subjects were women aged 25-59 years in the last three years prior to the study. Data were analyzed through Poisson regression using a hierarchical model. RESULTS: The proportion of women who did not undergo the Pap smear test in Fortaleza and Rio de Janeiro was 19.1% (95% CI: 16.1;22.1) and 16.5% (95% CI: 14.1;18.9), respectively. Higher prevalence ratios of cervical cancer screening failure in both cities were seen among women with low education and low per capita income, old age, unmarried, who never underwent mammography, clinical breast examination, and blood glucose and cholesterol level testing. Smokers also had lower screening rates compared to non-smoker women and this difference was only statistically significant in Rio de Janeiro. CONCLUSIONS:The study findings point to the need of intervention focusing particularly women in worse socioeconomic conditions and access to healthcare, old-aged and unmarried. Education activities must prioritize screening of asymptomatic women and early diagnosis for symptomatic women and access to adequate diagnostic methods and treatment should be provided.

Homicide and impunity: an ecological analysis at state level in Brazil

OBJECTIVE: To assess a new impunity index and variables that have been found to predict variation in homicide rates in other geographical levels as predictive of state-level homicide rates in Brazil. METHODS: This was a cross-sectional ecological study. Data from the mortality information system relating to the 27 Brazilian states for the years 1996 to 2005 were analyzed. The outcome variables were taken to be homicide victim rates in 2005, for the entire population and for men aged 20-29 years. Measurements of economic and social development, economic inequality, demographic structure and life expectancy were analyzed as predictors. An "impunity index", calculated as the total number of homicides between 1996 and 2005 divided by the number of individuals in prison in 2007, was constructed. The data were analyzed by means of simple linear regression and negative binomial regression. RESULTS: In 2005, state-level crude total homicide rates ranged from 11 to 51 per 100,000; for young men, they ranged from 39 to 241. The impunity index ranged from 0.4 to 3.5 and was the most important predictor of this variability. From negative binomial regression, it was estimated that the homicide victim rate among young males increased by 50% for every increase of one point in this ratio. CONCLUSIONS: Classic predictive factors were not associated with homicides in this analysis of state-level variation in Brazil. However, the impunity index indicated that the greater the impunity, the higher the homicide rate.

Effects of early life permethrin exposure on spatial working memory and on monoamine levels in different brain areas of pre-senescent rats

Pesticide exposure during brain development could represent an important risk factor for the onset of neurodegenerative diseases. Previous studies investigated the effect of permethrin (PERM) administered at 34 mg/kg, a dose close to the no observable adverse effect level (NOAEL) from post natal day (PND) 6 to PND 21 in rats. Despite the PERM dose did not elicited overt signs of toxicity (i.e. normal body weight gain curve), it was able to induce striatal neurodegeneration (dopamine and Nurr1 reduction, and lipid peroxidation increase). The present study was designed to characterize the cognitive deficits in the current animal model. When during late adulthood PERM treated rats were tested for spatial working memory performances in a T-maze-rewarded alternation task they took longer to choose for the correct arm in comparison to age matched controls. No differences between groups were found in anxiety-like state, locomotor activity, feeding behavior and spatial orientation task. Our findings showing a selective effect of PERM treatment on the T-maze task point to an involvement of frontal cortico-striatal circuitry rather than to a role for the hippocampus. The predominant disturbances concern the dopamine (DA) depletion in the striatum and, the serotonin (5-HT) and noradrenaline (NE) unbalance together with a hypometabolic state in the medial prefrontal cortex area. In the hippocampus, an increase of NE and a decrease of DA were observed in PERM treated rats as compared to controls. The concentration of the most representative marker for pyrethroid exposure (3-phenoxybenzoic acid) measured in the urine of rodents 12 h after the last treatment was 41.50 µ/L and it was completely eliminated after 96 h.

Environmental lead poisoning among children in Porto Alegre state, Southern Brazil

OBJECTIVE: To estimate the prevalence of lead poisoning in children and to identify associated factors, as well as possible local sources of contamination. METHODS: A cross-sectional prevalence study conducted in 2006 with a random sample of 97 children age zero to five years from a neighborhood in Porto Alegre, Southern Brazil. Blood lead levels were measured and a questionnaire administered to collect information on sociodemographics, recycling and dwelling. A preliminary environmental evaluation was carried out with direct analysis of soil and indirect analysis of air pollution with bioindicators to identify possible sources of contamination. To analyze lead concentrations from the different collection sites, for each type of material studied, ANOVA was performed with a Brown-Forsythe adjustment for heteroscedasticity and with Dunnett's T3 procedure for multiple comparisons of unequal variances. RESULTS: Blood lead levels > 10.0 µg/dL was found in 16.5% of children. Recycling of waste at home, low father's education level, and increased age of children were associated with increase blood lead levels. High lead levels were found in soil, and there was little indication of lead air pollution. CONCLUSIONS: A high prevalence of lead poisoning was identified, and the potential sources of contamination in this community appear related to waste recylcing activities. Studies should be conducted with other populations of Brazilian children and evaluate potential sources of local and general contamination, to accurately characterize this issue in Brazil.

Dermic diffusion and stratum corneum: a state of the art review of mathematical models

Transdermal biotechnologies are an ever increasing field of interest, due to the medical and pharmaceutical applications that they underlie. There are several mathematical models at use that permit a more inclusive vision of pure experimental data and even allow practical extrapolation for new dermal diffusion methodologies. However, they grasp a complex variety of theories and assumptions that allocate their use for specific situations. Models based on Fick's First Law found better use in contexts where scaled particle theory Models would be extensive in time-span but the reciprocal is also true, as context of transdermal diffusion of particular active compounds changes. This article reviews extensively the various theoretical methodologies for studying dermic diffusion in the rate limiting dermic barrier, the stratum corneum, and systematizes its characteristics, their proper context of application, advantages and limitations, as well as future perspectives.

Aedes aegypti entomological indices in an endemic area for dengue in Sao Paulo State, Brazil

OBJECTIVE: To evaluate the most productive types of properties and containers for Aedes aegypti and the spatial distribution of entomological indices.METHODS: Between December 2006 and February 2007, the vector's immature forms were collected to obtain entomological indices in 9,875 properties in the Jaguare neighborhood of Sao Jose do Rio Preto, SP, Southeastern Brazil. In March and April 2007, a questionnaire about the conditions and characteristics of properties was administered. Logistic regression was used to identify variables associated with the presence of pupae at the properties. Indices calculated per block were combined with a geo-referenced map, and thematic maps of these indices were obtained using statistical interpolation.RESULTS: The properties inspected had the following Ae. aegypti indices: Breteau Index = 18.9, 3.7 larvae and 0.42 pupae per property, 5.2 containers harboring Ae. aegypti per hectare, 100.0 larvae and 11.6 pupae per hectare, and 1.3 larvae and 0.15 pupae per inhabitant. The presence of yards, gardens and animals was associated with the presence of pupae.CONCLUSIONS: Specific types of properties and containers that simultaneously had low frequencies among those positive for the vector and high participation in the productivity of larvae and pupae were not identified. The use of indices including larval and pupal counts does not provide further information beyond that obtained from the traditional Stegomyia indices in locations with characteristics similar to those of São José do Rio Preto. The indices calculated per area were found to be more accurate for the spatial assessment of infestation. The Ae. aegypti infestation levels exhibited extensive spatial variation, indicating that the assessment of infestation in micro areas is needed.

Quality-of-service in wireless sensor networks: state-of-the-art and future directions

Wireless sensor networks (WSNs) are one of today’s most prominent instantiations of the ubiquituous computing paradigm. In order to achieve high levels of integration, WSNs need to be conceived considering requirements beyond the mere system’s functionality. While Quality-of-Service (QoS) is traditionally associated with bit/data rate, network throughput, message delay and bit/packet error rate, we believe that this concept is too strict, in the sense that these properties alone do not reflect the overall quality-ofservice provided to the user/application. Other non-functional properties such as scalability, security or energy sustainability must also be considered in the system design. This paper identifies the most important non-functional properties that affect the overall quality of the service provided to the users, outlining their relevance, state-of-the-art and future research directions.

The isolation and characterization of cytochrome c nitrite reductase subunits (NrfA and NrfH) from Desulfovibrio desulfuricans ATCC 27774

Eur. J. Biochem. 270, 3904–3915 (2003)

Broad-temperature range spectroscopy of the two-centre modular redox metalloprotein Desulfovibrio desulfuricans desulfoferrodoxin

Dalton Trans., 2003, 3328-3338

Bilirubin directly disrupts membrane lipid polarity and fluidity, protein order, and redox status in rat mitochondria

Background/Aims: Unconjugated bilirubin (UCB) impairs crucial aspects of cell function and induces apoptosis in primary cultured neurones. While mechanisms of cytotoxicity begin to unfold, mitochondria appear as potential primary targets. Methods: We used electron paramagnetic resonance spectroscopy analysis of isolated rat mitochondria to test the hypothesis that UCB physically interacts with mitochondria to induce structural membrane perturbation, leading to increased permeability, and subsequent release of apoptotic factors. Results: Our data demonstrate profound changes on mitochondrial membrane properties during incubation with UCB, including modified membrane lipid polarity and fluidity (P , 0:01), as well as disrupted protein mobility(P , 0:001). Consistent with increased permeability, cytochrome c was released from the intermembrane space(P , 0:01), perhaps uncoupling the respiratory chain and further increasing oxidative stress (P , 0:01). Both ursodeoxycholate, a mitochondrial-membrane stabilising agent, and cyclosporine A, an inhibitor of the permeability transition, almost completely abrogated UCB-induced perturbation. Conclusions: UCB directly interacts with mitochondria influencing membrane lipid and protein properties, redox status, and cytochrome c content. Thus, apoptosis induced by UCB may be mediated, at least in part, by physical perturbation of the mitochondrial membrane. These novel findings should ultimately prove useful to our evolving understanding of UCB cytotoxicity.

Body image in Brazil: recent advances in the state of knowledge and methodological issues

OBJECTIVE To analyze Brazilian literature on body image and the theoretical and methodological advances that have been made. METHODS A detailed review was undertaken of the Brazilian literature on body image, selecting published articles, dissertations and theses from the SciELO, SCOPUS, LILACS and PubMed databases and the CAPES thesis database. Google Scholar was also used. There was no start date for the search, which used the following search terms: “body image” AND “Brazil” AND “scale(s)”; “body image” AND “Brazil” AND “questionnaire(s)”; “body image” AND “Brazil” AND “instrument(s)”; “body image” limited to Brazil and “body image”. RESULTS The majority of measures available were intended to be used in college students, with half of them evaluating satisfaction/dissatisfaction with the body. Females and adolescents of both sexes were the most studied population. There has been a significant increase in the number of available instruments. Nevertheless, numerous published studies have used non-validated instruments, with much confusion in the use of the appropriate terms (e.g., perception, dissatisfaction, distortion). CONCLUSIONS Much more is needed to understand body image within the Brazilian population, especially in terms of evaluating different age groups and diversifying the components/dimensions assessed. However, interest in this theme is increasing, and important steps have been taken in a short space of time.