The isatin-Schiff base copper(II) complex Cu(isaepy)(2) acts as delocalized lipophilic cation, yields widespread mitochondrial oxidative damage and induces AMP-activated protein kinase-dependent apoptosis

We previously demonstrated that Bis[(2-oxindol-3-ylimino)-2-(2-aminoethyl) pyridine-N, N`] copper(II) [Cu(isaepy)(2)] was an efficient inducer of the apoptotic mitochondrial pathway. Here, we deeply dissect the mechanisms underlying the ability of Cu(isaepy)(2) to cause mitochondriotoxicity. In particular, we demonstrate that Cu(isaepy)(2) increases NADH-dependent oxygen consumption of isolated mitochondria and that this phenomenon is associated with oxy-radical production and insensitive to adenosine diphosphate. These data indicate that Cu(isaepy)(2) behaves as an uncoupler and this property is also confirmed in cell systems. Particularly, SH-SY5Y cells show: (i) an early loss of mitochondrial transmembrane potential; (ii) a decrease in the expression levels of respiratory complex components and (iii) a significant adenosine triphosphate (ATP) decrement. The causative energetic impairment mediated by Cu(isaepy)(2) in apoptosis is confirmed by experiments carried out with rho(0) cells, or by glucose supplementation, where cell death is significantly inhibited. Moreover, gastric and cervix carcinoma AGS and HeLa cells, which rely most of their ATP production on oxidative phosphorylation, show a marked sensitivity toward Cu(isaepy)(2). Adenosine monophosphate-activated protein kinase (AMPK), which is activated by events increasing the adenosine monophosphate: ATP ratio, is deeply involved in the apoptotic process because the overexpression of its dominant/negative form completely abolishes cell death. Upon glucose supplementation, AMPK is not activated, confirming its role as fuel-sensing enzyme that positively responds to Cu(isaepy)(2)-mediated energetic impairment by committing cells to apoptosis. Overall, data obtained indicate that Cu(isaepy)(2) behaves as delocalized lipophilic cation and induces mitochondrial-sited reactive oxygen species production. This event results in mitochondrial dysfunction and ATP decrease, which in turn triggers AMPK-dependent apoptosis.

Oncostatin M is a novel glucocorticoid-dependent neuroinflammatory factor that enhances oligodendrocyte precursor cell activity in demyelinated sites

The innate immune reaction to tissue injury is a natural process, which can have detrimental effects in the absence of negative feedbacks by glucocorticoids (GCs). Although acute lipopolysaccharide (LPS) challenge is relatively harmless to the brain parenchyma of adult animals, the endotoxin is highly neurotoxic in animals that are treated with the GC receptor antagonist RU486. This study investigated the role of cytokines of the gp130-related family in these effects, because they are essential components of the inflammatory process that provide survival signals to neurons. Intracerebral LPS injection stimulated expression of several members of this family of cytokines, but oncostatin M (Osm) was the unique ligand to be completely inhibited by the RU486 treatment. OSM receptor (Osmr) is expressed mainly in astrocytes and endothelial cells following LPS administration and GCs are directly responsible for its transcriptional activation in the presence of the endotoxin. In a mouse model of demyelination, exogenous OSM significantly modulated the expression of genes involved in the mobilization of oligodendrocyte precursor cells (OPCs), differentiation of oligodendrocyte, and production of myelin. In conclusion, the activation of OSM signaling is a mechanism activated by TLR4 in the presence of negative feedback by GCs on the innate immune system of the brain. OSM absence is associated with detrimental effects of LPS, whereas exogenous OSM favors repair response to demyelinated regions. (C) 2010 Elsevier Inc. All rights reserved.

Nanogravimetric study of the complex voltammetric response in the electro-oxidation of methanol on platinum

Instead of a time-invariant voltammetric profile, many electrochemical systems display a cycle-dependent current-potential response. This phenomenon has been referred to as complex voltammetric response and it has been observed during the electro-oxidation of several molecules such as methanol, ethanol, propanol and hydrogen. There are currently two explanations for the surface mechanism underlying this behavior. In one scenario, the complex voltammogram would result from the specific kinetic pathway taken during the forward sweep. In the other explanation, the phenomenon is discussed in terms of the interplay among the surface roughening and subsequent relaxation, and the ohmic drop coupled to a negative differential resistance. We report in this paper a nanogravimetric investigation of the complex voltammetric response in the electro-oxidation of methanol on platinum electrode in both acidic and alkaline media. Different periodic patterns composed of intercalated small and large hysteresis cycles were observed as a function of the applied voltage and the series resistance between the working electrode and the potentiostat. Independently, nanogravimetric results indicated no detectable difference in the delta-frequency versus voltage profile between small and large hysteresis cycles. These findings were interpreted as experimental evidence of the secondary, if any, role played by the very electrochemical reaction on the emergence of complex voltammetric response. (C) 2009 Elsevier Ltd. All rights reserved.

Model selection, estimation and forecasting in VAR models with short-run and long-run restrictions

We study the joint determination of the lag length, the dimension of the cointegrating space and the rank of the matrix of short-run parameters of a vector autoregressive (VAR) model using model selection criteria. We consider model selection criteria which have data-dependent penalties for a lack of parsimony, as well as the traditional ones. We suggest a new procedure which is a hybrid of traditional criteria and criteria with data-dependant penalties. In order to compute the fit of each model, we propose an iterative procedure to compute the maximum likelihood estimates of parameters of a VAR model with short-run and long-run restrictions. Our Monte Carlo simulations measure the improvements in forecasting accuracy that can arise from the joint determination of lag-length and rank, relative to the commonly used procedure of selecting the lag-length only and then testing for cointegration.

Model selection, estimation and forecasting in VAR models with short-run and long-run restrictions

We study the joint determination of the lag length, the dimension of the cointegrating space and the rank of the matrix of short-run parameters of a vector autoregressive (VAR) model using model selection criteria. We consider model selection criteria which have data-dependent penalties as well as the traditional ones. We suggest a new two-step model selection procedure which is a hybrid of traditional criteria and criteria with data-dependant penalties and we prove its consistency. Our Monte Carlo simulations measure the improvements in forecasting accuracy that can arise from the joint determination of lag-length and rank using our proposed procedure, relative to an unrestricted VAR or a cointegrated VAR estimated by the commonly used procedure of selecting the lag-length only and then testing for cointegration. Two empirical applications forecasting Brazilian inflation and U.S. macroeconomic aggregates growth rates respectively show the usefulness of the model-selection strategy proposed here. The gains in different measures of forecasting accuracy are substantial, especially for short horizons.

Model selection, estimation and forecasting in VAR models with short-run and long-run restrictions

We study the joint determination of the lag length, the dimension of the cointegrating space and the rank of the matrix of short-run parameters of a vector autoregressive (VAR) model using model selection criteria. We consider model selection criteria which have data-dependent penalties as well as the traditional ones. We suggest a new two-step model selection procedure which is a hybrid of traditional criteria and criteria with data-dependant penalties and we prove its consistency. Our Monte Carlo simulations measure the improvements in forecasting accuracy that can arise from the joint determination of lag-length and rank using our proposed procedure, relative to an unrestricted VAR or a cointegrated VAR estimated by the commonly used procedure of selecting the lag-length only and then testing for cointegration. Two empirical applications forecasting Brazilian in ation and U.S. macroeconomic aggregates growth rates respectively show the usefulness of the model-selection strategy proposed here. The gains in di¤erent measures of forecasting accuracy are substantial, especially for short horizons.

Imperfectly credible disinflation under endogenous time-dependent pricing

The real effects of an imperfectly credible disinflation depend critically on the extent of price rigidity. Therefore, the study of how policymakers’ credibility affects the outcome of an announced disinflation should not be dissociated from the analysis of the determinants of the frequency of price adjustments. In this paper we examine how the policymaker’s credibility affects the outcome of an announced disinflation in a model with endogenous time-dependent pricing rules. Both the initial degree of price ridigity, calculated optimally, and, more notably, the changes in contract length during disinflation play an important role in the explanation of the effects of imperfect credibility. We initially evalute the costs of disinflation in a setup where credibility is exogenous, and then allow agents to update beliefs about the “type” of monetary authority that they face. We show that, in both cases, the interaction between the endogeneity of time-dependent rules and imperfect credibility increases the output costs of disinflation.

Is what you say what you do? Analyzing and comparing the effect of buyer-supplier relationship in the Brazilian and Chinese supplier selection criteria

Choosing properly and efficiently a supplier has been challenging practitioners and academics since 1960’s. Since then, countless studies had been performed and relevant changes in the business scenario were considered such as global sourcing, quality-orientation, just-in-time practices. It is almost consensus that quality should be the selection driver, however, some polemical findings questioned this general agreement. Therefore, one of the objectives of the study was to identify the supplier selection criteria and bring this discussion back again. Moreover, Dickson (1966) suggested existing business relationship as selection criterion, then it was reviewed the importance of business relationship for the company and noted a set of potential negative effects that could rise from it. By considering these side effects of relationship, this research aimed to investigate how the relationship could influence the supplier selection and how its harmful effects could affect the selection process. The impact of this phenomenon was investigated cross-nationally. The research strategy adopted was a controlled experiment via vignette combined with discrete choice analysis. The data collections were performed in China and Brazil. By examining the results, it could be drawn five major findings. First, when purchasers were asked to declare their supplier selection priorities, quality was stated as the most important independently of country and relationship. This result was consistent with diverse studies since 60’s. However, when purchasers were exposed to a multi-criteria trade-off situation, their actual selection priorities deviate from what they had declared. In the actual decision-making without influence of buyer-supplier relationship, Brazilian purchasers focused on price and Chinese buyers prioritized delivery then price. This observation reinforced some controversial prior studies of Verma & Pullman (1998) and Hirakubo & Kublin (1998). Second, through the introduction of the buyer-supplier relationship (operationalized via relational capital) in the supplier selection process, this research extended the existing studies and found that Brazilian buyers still focused on price. The relationship became just another criterion for supplier selection such as quality and delivery. However, from the Chinese sample, the results suggested that quality was totally discarded and the decision was majorly made through price and relationship. The third finding suggested that relational capital could legitimate the quality and sustainability of the supplier and replaces these selection criteria and made the decisional task less complex. Additionally, with the relational capital, the decision-makings were associated to few biases such as availability cognition, commitment, confirmatory and perceived biases. By analyzing the purchasers’ behavior, relational capital inducted buyers of both countries to relax in their purchasing requirements (quality, delivery and sustainability) leading to potential negative effects. In the Brazilian sample, the phenomenon of willing to pay a higher price for a lower quality offer demonstrated to be a potential counterproductive and suboptimal decision. Finally, the last finding was associated to the cultural effect on the buyers’ decisions. From the outcome, it is possible to observe that if a purchaser’s cultural background is more relation-oriented, the more he will tend to use relational capital as a decision heuristic, thus, the purchaser will be more susceptible to the potential relationship’s side effects

Time-dependent or state-dependent pricing? Evidence from a large devaluation episode

State-dependent and time-dependent price setting models yield distinct implications for how frequency and magnitude of price changes react to shocks. This note studies pricing behavior in Brazil following the large devaluation of the Brazilian Real in 1999 to distinguish between models. The results are consistent with state-dependent pricing

Time-dependent or state-dependent pricing? Evidence from firms’ response to inflation shocks

This paper proposes a test for distinguishing between time-dependent and state-dependent pricing based on whether the timing of pricing changes is affected by realized or expeted inflation. Using Brazilian data and exploring a large discrepancy between realized and expected inflation in 2002-3, we obtain a strong relation between expected inflation and duration of price spells, but little effect of inflation shocks on the frequency of price adjustment. The results thus support models with timedependent pricing, where the timing for following changes is optimally chosen whenever firms adjust prices

Estudos analíticos dos grafoelementos do eletroencefalograma em sono: fusos do sono, ondas agudas do vértex e o gradiente de freqüência e amplitude, como indicadores de comprometimento neurológico na criança

Innumerable studies have focused been reported on the sleep spindles (SS), Sharp Vertex Waves (SVW) and REM, NREM Sleep as indicators interpreting EEG patterns in children. However, Frequency and Amplitud Gradient (FAG) is rarely cited sleep parameter in children,that occurs during NREM Sleep. It was first described by Slater and Torres, in 1979, but has not been routinely evaluated in EEG reports. The aim of this study was to assess the absence of SS, SVW and FAG, as an indication of neurological compromise in children. The sample consisted of 1014 EEGs of children referred to the Clinical Neurophysiology Laboratory, Hospital Universitário de Brasília (HUB), from January 1997 to March 2003, with ages ranging from 3 months to 12 years old, obtained in spontaneous sleep or induced by choral hydrate. The study was transversal and analytical, in which, visual analysis of EEG traces was perfumed individually and independently by two electroencephalographers without prior knowledge of the EEG study or neurological findings. After EEG selection, the investigators analyzed the medical reports in order to define and correlate neurological pattern was classified according to the presence or absence of neurological compromise, as Normal Neurological Pattern (NNP), and Altered Neurological Pattern (ANP) respectively. From the visual analysis of the EEG(s), it was possible to characterize 6 parameters: 1- FAG present (64,1%); 2- FAG absent (35,9%); 3 - normal SS (87,9%); 4 - altered SS s (12,1%); 5 - normal SVW s (95,7%); 6 - altered SVW s (4,3%). The prevalence of well-formed FAG is found in the 3 months to 5 years age group in the children with NNF. FAG was totally absent from the age of 10 years. When comparing the three sleep graphielements, it was observed that SVW and SS were predominant in children with NNF. However, FAG absent was more prevalent in the ANF than in altered SS an SVW. The statistical analysis showed that there is a strong association of FAG absent, with isolated alteration, in ANF patients, in that the prevalence ratio was 6,60. The association becomes stronger when FAG absent + altered SS(s) is considered (RP= 6,68). Chi-square test, corrected by Yates technique, showed a highly significant relation for FAG ρ= 0,00000001, for error X of 5%, or else the 95% confidence interval (ρ<0,05). Thus, the FAG absent were more expressive in ANF patient than altered SS(s) and SVW(s). The association becomes stronger in order to establish a prognostic relation, when the FAG is combined with the SS. The results os this study allow us to affirm that the FAG, when absent at ages ranging from 3 months to 5 years , is an indication of neurological compromise. FAG is an age-dependent EEG parameter and incorporated systematically, in the interpretation criteria of the EEG of children s sleep, not only in the maturational point of view, but also neurological disturbances with encephalic compromise

Are the preference and selection patterns of hermit crabs for gastropod shells species- or site-specific?

Experimental analyses of hermit crabs and their preferences for shells are essential to understand the intrinsic relationship of the crabs' dependence on shells, and may be useful to explain their shell use pattern in nature. The aim of this study was to evaluate the effect of crab species and site on the pattern of shell use, selection, and preference in the south-western Atlantic hermit crabs Pagurus brevidactylus and Pagurus criniticornis, comparing sympatric and allopatric populations. Differently from the traditional approach to evaluate shell preference by simply determining the shell selection pattern (i.e., the number of shells of each type selected), preference was defined (according to [Liszka, D., Underwood, AJ., 1990. An experimental design to determine preferences for gastropod shells by a hermit-crab. J. Exp. Mar. Biol. Ecol., 137(1), 47-62]) by the comparison of the number of crabs changing for a particular shell type when three options were given (Cerithium atratum, Morula nodulosa, and Tegula viridula) with the number of crabs changing for this same type when only this type was offered. The effect of crab species was tested at Cabelo Gordo Beach, where P. brevidacrylus was found occupying shells of C. atratum, M. nodulosa, and T viridula in similar frequencies, whereas P. criniticornis occupied predominantly shells of C atratum. In laboratory experiments the selection patterns of the two hermit-crab species for these three gastropods were different, with P criniticornis selecting mainly shells of C atratum, and R brevidactylus selecting more shells of M. nodulosa. The shell preference was also dependent on crab species, with P. criniticornis showing a clear preference for shells of C atratum, whereas P. brevidactylus did not show a preference for any of the tested shells. The effect of site was tested for the two species comparing data from Cabelo Gordo to Preta (P brevidactylus) and Araca beaches (P. criniticornis). The pattern of shell use, selection, and preference was demonstrated to be dependent on site only for P. brevidactylus. The results also showed that the shell use pattern of P criniticornis can be explained by its preference at both sites, whereas for P. brevidactylus it occurred only at Cabelo Gordo, where the absence of preference was correlated with the similar use of the three gastropod species studied. Finally, the results showed that the shell selection pattern cannot be considered as a measure of shell preference, since it overestimates crab selectivity. (C) 2009 Elsevier B.V. All rights reserved.

Candidíase vulvovaginal: sintomatologia, fatores de risco e colonização anal concomitante

Post-menarche patients with clinical signs of vulvovaginitis were analyzed in this study, whose aims were the following: identify the frequency of C. albicans and non C. albicans species and negative results, correlate the vaginal culture for yeast with risk factors and symptomatology; compare positive and negative results for yeast in the vaginal and anal cultures; compare the positive results for C. albicans with other results found in the vaginal and anal cultures; and compare concomitant positivity for C. albicans and non C. albicans in the vaginal and anal cultures. Sample selection occurred between May, 2003 and May, 2005, and included 99 patients from Natal, Brazil. The laboratory methods used consisted of CHROMagar Candida culture medium, thermotolerance test at 42-45°C and hypertonic NaCL, in addition to the classic methods of carbohydrate assimilation and fermentation. We used absolute numbers, percentages, means of central tendency, chi-squared test (χ2) with Yates correction, Fisher s exact test and odds ratio for statistical analysis. The most frequent species was C. albicans in 69% of the cases. The positivity for Candida spp showed an association with the use of tight-fitting intimate clothing and/or synthetics, allergic diseases and the occurrence of itching, leukorrhea and erythema. Anal colonization increased the likelihood of vaginal contamination by 2.8 and 4.9 times, respectively, for Candida spp and C. albicans. When compared to the other species, C. albicans-positive anal colonization increased by 3.7 times the likelihood of vaginal positivity. These data suggest likely vaginal contamination originating in the anus

Preliminary study on age- and sex-dependent alterations in the composition of skeletal muscle fibers of Brasileiro de Hipismo horses

The aim of this work was to characterize the distribution of myofibers in the gluteus medius muscle of inactive horses of the Brasileiro de Hipismo (BH) breed at different ages by means of histochemical analyses, according to sex and depth of the biopsy. A total of 78 inactive horses (9 castrated males, 35 stallions, and 34 females) of the BH breed, aged 1 to 4 years, were used. A percutaneous muscle biopsy was obtained with a 6.0-mm Bergstrom-type needle, which allowed the removal of muscle fragments at depths of 20 and 60 mm. Myofiber types were determined based on myofibrillar adenosine triphosphatase (mATPase) and nicotinamide dinucleotide tetrazolium reductase (NADH-TR) techniques. Morphometry of the fibers was determined based on cross-sectional area (CSA), mean frequency (F), and relative cross-sectional area (RCSA). The current study demonstrated that BH horses 3 and 4 years of age show a greater percentage of, and area occupied by, type IIA fibers and lower percentage of type IIX fibers in the gluteus medius muscle compared with horses 1 and 2 years of age. No difference was found between sexes in the frequency of and area occupied by the different fiber types at any of the depths and ages studied. In this study, females showed a greater CSA for all fibers in comparison with males, at 1 year of age. The results of the current study indicate that the gluteus medius muscle of inactive BH horses shows modifications in its structural and biochemical composition during the growth of the animals, leading to a better oxidative capacity.

Genetic similarity between staphylococcus sp isolated from human and hospital settings, and susceptibility to different antimicrobials

Foram coletadas 143 amostras de mãos de humanos e camas hospitalares, através de swabs no caldo BHI, em um hospital escola da cidade de Ribeirão Preto/SP. As amostras coletadas foram incubadas a 37ºC por 24 horas e após este período as culturas foram semeadas em placas de Petri contendo agar Staphylococcus Médium 110. As colônias típicas do gênero Staphylococcus foram colhidas e estocados a 4ºC até o momento de elaboração das provas de catalase, manitol, hemólise, DNAse e coagulase. As cepas isoladas foram analisadas através da técnica de RAPD-PCR para verificar o grau de similaridade. A sensibilidade das cepas isoladas foi testada frente a 10 diferentes antibióticos. Das 92 cepas de Staphylococcus sp isoladas, 67 (72,8%) foram identificados como Staphylococcus coagulase-negativas e 25 (27,2%) como Staphylococcus coagulase-positivas. A análise de similaridade mostrou uma grande heterogeneidade entre as cepas, entretanto foram isoladas algumas cepas com 100% de similaridade. Resistência a oxacilina foi encontrada em 39 (42%) cepas. Duas cepas de estafilococos coagulase-negativos mostraram-se resistentes a vancomicina. Onze cepas (12%) de estafilococos foram consideradas multirresistentes. Medidas de desinfecção das mãos de pessoal e dos leitos hospitalares e a racionalização do uso indiscriminado de antibióticos podem contribuir para a queda da transmissão de patógenos e diminuição da pressão de seleção, e conseqüentemente diminuindo a freqüência e letalidade das infecções nosocomiais.