Granulocyte Colony-stimulating Factor Reduces Mortality by Suppressing Ventricular Arrhythmias in Acute Phase of Myocardial Infarction in Rats

Our aim was to evaluate the effects of granulocyte colony-stimulating factor (G-CSF) on early cardiac arrhythmias after myocardial infarction (MI) and the impact on survival. Male Wistar rats received repeated doses of 50 mu g/kg G-CSF (MI-GCSF group) or vehicle (MI group) at 7, 3, and 1 days before surgery. MI was induced by permanent occlusion of left corollary artery. The electrocardiogram was obtained before occlusion and then for 30 minutes after surgery. Events and duration of ventricular arrhythmias were analyzed. The levels of connexin43 (Cx43) were measured by Western blot immediately before MI production. Survival was significantly increased in MI-GCSF pretreated group (74% versus 52.0% MI. P < 0.05). G-CSF pretreatment also significantly reduced the ventricular premature beats when compared with the untreated-MI group (201 +/- 47 versus 679 +/- 117, P < 0.05). The number and the duration of ventricular tachycardia were smaller in the MI-G-CSF group, as well as the number of ventricular fibrillation episodes (10% versus 69% in NIL P < 0.05). Cx43 levels were significantly increased by G-CSF treatment (1.27 +/- 0.13 versus 0.86 +/- 0.11; P < 0.05). The MI size 24 hours after occlusion was reduced by G-CSF pretreatment (36 +/- 3% versus 44 +/- 2% of left ventricle in MI group; P < 0.05). The increase of Cx43 expression in the heart may explain the reduced incidence in ventricular arrhythmias in the early phases after coronary artery occlusion in rats, thus increasing survival after MI.

Long-Term Culture of Mouse Embryonic Stem Cell-Derived Adherent Neurospheres and Functional Neurons

Innumerous protocols, using the mouse embryonic stem (ES) cells as model for in vitro study of neurons functional properties and features, have been developed. Most of these protocols are short lasting, which, therefore, does not allow a careful analysis of the neurons maturation, aging, and death processes. We describe here a novel and efficient long-lasting protocol for in vitro ES cells differentiation into neuronal cells. It consists of obtaining embryoid bodies, followed by induction of neuronal differentiation with retinoic acid of nonadherent embryoid bodies (three-dimensional model), which further allows their adherence and formation of adherent neurospheres (AN, bi-dimensional model). The AN can be maintained for at least 12 weeks in culture under repetitive mechanical splitting, providing a constant microenvironment (in vitro niche) for the neuronal progenitor cells avoiding mechanical dissociation of AN. The expression of neuron-specific proteins, such as nestin, sox1, beta III-tubulin, microtubule-associated protein 2, neurofilament medium protein, Tau, neuronal nuclei marker, gamma-aminobutyric acid, and 5-hydroxytryptamine, were confirmed in these cells maintained during 3 months under several splitting. Additionally, expression pattern of microtubule-associated proteins, such as lissencephaly (Lis1) and nuclear distribution element-like (Ndel1), which were shown to be essential for differentiation and migration of neurons during embryogenesis, was also studied. As expected, both proteins were expressed in undifferentiated ES cells, AN, and nonrosette neurons, although presenting different spatial distribution in AN. In contrast to previous studies, using cultured neuronal cells derived from embryonic and adult tissues, only Ndel1 expression was observed in the centrosome region of early neuroblasts from AN. Mature neurons, obtained from ES cells in this work, display ionic channels and oscillations of membrane electrical potential typical of electrically excitable cells, which is a characteristic feature of the functional central nervous system (CNS) neurons. Taken together, our study demonstrated that AN are a long-term culture of neuronal cells that can be used to analyze the process of neuronal differentiation dynamics. Thus, the protocol described here provides a new experimental model for studying neurological diseases associated with neuronal differentiation during early development, as well as it represents a novel source of functional cells that can be used as tools for testing the effects of toxins and/or drugs on neuronal cells.

Impaired dendritic cell differentiation and maturation in the absence of C3

Human monocytes can be differentiated into immature dendritic cells (DCs) in the presence of serum and cytokines. One of the main functions of immature DCs is to capture and process antigens. Following maturation, they differentiate into antigen presenting cells. The role of complement in the differentiation process from monocytes towards immature DCs remains elusive. Here we demonstrate that complement 3 (C3) has a regulatory impact on the expression of specific DC surface molecules and DC-derived cytokine production during DC differentiation. We isolated human adherent peripheral blood mononuclear cells, which were cultured in the presence of GM-CSF plus IL-4 in medium supplemented with normal human serum or C3 deficient serum. The lack of C3 during DC differentiation negatively impacted the expression of C-type lectin receptor DC-SIGN, the antigen presenting molecules HLA-DR and CD1a, and the costimulatory molecules CD80 and CD86. Further, the spontaneous production of IL-6 and IL-12 was reduced in the absence of C3. Moreover, the maturation of immature DCs in response to LPS challenge was impaired in the absence of C3 as evidenced by reduced MHC-II, co-stimulatory molecule expression as well as modulated IL-12 and TNF-alpha production. Collectively, our results provide evidence for a novel role of C3 as a critical cofactor in human DC differentiation and maturation. (C) 2007 Elsevier Ltd. All rights reserved.

Single-use Trocar Is it Possible to Reprocess it After the First Use?

The aim of this study was to verify and describe the presence of microorganisms in the single-use trocar after its use in surgical procedures, and after this device was submitted to cleaning, conditioning, and sterilization by physicochemical processes (formaldehyde, ethylene oxide, and hydrogen peroxide plasma). Twenty-eight trocars of the Ethicon, Auto-suture, and Aesculap brands, were randomly selected and analyzed after laparoscopic cholecystectomy. The results have shown that cultures grown of the material collected from the trocars, immediately after its use and before its sterilization process, showed the presence of bacteria and fungi in 46.5% (13). In 53.5% (15) of the trocars, the presence of microorganisms was not detected, very likely due to niche`s scarcity. In the cultures grown of the 28 trocars after being submitted to sterilization processes, the presence of microorganisms was not verified. We can therefore conclude that although trocars possess compartments not easily accessed for cleaning, these devices can be adequately cleaned and effectively sterilized, when well manipulated, in the institution where the study was carried out by the processes of steam sterilization at low temperature and formaldehyde, ethylene oxide, and hydrogen peroxide plasma.

Comparing machine learning classifiers in potential distribution modelling

Species` potential distribution modelling consists of building a representation of the fundamental ecological requirements of a species from biotic and abiotic conditions where the species is known to occur. Such models can be valuable tools to understand the biogeography of species and to support the prediction of its presence/absence considering a particular environment scenario. This paper investigates the use of different supervised machine learning techniques to model the potential distribution of 35 plant species from Latin America. Each technique was able to extract a different representation of the relations between the environmental conditions and the distribution profile of the species. The experimental results highlight the good performance of random trees classifiers, indicating this particular technique as a promising candidate for modelling species` potential distribution. (C) 2010 Elsevier Ltd. All rights reserved.

Culture-area relation in Axelrod`s model for culture dissemination

Axelrod`s model for culture dissemination offers a nontrivial answer to the question of why there is cultural diversity given that people`s beliefs have a tendency to become more similar to each other`s as they interact repeatedly. The answer depends on the two control parameters of the model, namely, the number F of cultural features that characterize each agent, and the number q of traits that each feature can take on, as well as on the size A of the territory or, equivalently, on the number of interacting agents. Here, we investigate the dependence of the number C of distinct coexisting cultures on the area A in Axelrod`s model, the culture-area relationship, through extensive Monte Carlo simulations. We find a non-monotonous culture-area relation, for which the number of cultures decreases when the area grows beyond a certain size, provided that q is smaller than a threshold value q (c) = q (c) (F) and F a parts per thousand yen 3. In the limit of infinite area, this threshold value signals the onset of a discontinuous transition between a globalized regime marked by a uniform culture (C = 1), and a completely polarized regime where all C = q (F) possible cultures coexist. Otherwise, the culture-area relation exhibits the typical behavior of the species-area relation, i.e., a monotonically increasing curve the slope of which is steep at first and steadily levels off at some maximum diversity value.

Inactivation of formyltransferase (wbkC) gene generates a Brucella abortus rough strain that is attenuated in macrophages and in mice

Rough mutants of Brucella abortus were generated by disruption of wbkC gene which encodes the formyltransferase enzyme involved in LPS biosynthesis. In bone marrow-derived macrophages the B. abortus Delta wbkC mutants were attenuated, could not reach a replicative niche and induced higher levels of IL-12 and TNF-alpha when compared to parental smooth strains. Additionally, mutants exhibited attenuation in vivo in C57BL/6 and interferon regulatory factor-1 knockout mice. Delta wbkC mutant strains induced lower protective immunity in C56BL/6 than smooth vaccine S19 but similar to rough vaccine RB51. Finally, we demonstrated that Brucella wbkC is critical for LPS biosynthesis and full bacterial virulence. (C) 2010 Elsevier Ltd. All rights reserved.

Cutpoint selection for discretizing a continuous covariate for generalized estimating equations

We consider consider the problem of dichotomizing a continuous covariate when performing a regression analysis based on a generalized estimation approach. The problem involves estimation of the cutpoint for the covariate and testing the hypothesis that the binary covariate constructed from the continuous covariate has a significant impact on the outcome. Due to the multiple testing used to find the optimal cutpoint, we need to make an adjustment to the usual significance test to preserve the type-I error rates. We illustrate the techniques on one data set of patients given unrelated hematopoietic stem cell transplantation. Here the question is whether the CD34 cell dose given to patient affects the outcome of the transplant and what is the smallest cell dose which is needed for good outcomes. (C) 2010 Elsevier BM. All rights reserved.

Methods for Equivalence and Noninferiority Testing

Classical hypothesis testing focuses on testing whether treatments have differential effects on outcome. However, sometimes clinicians may be more interested in determining whether treatments are equivalent or whether one has noninferior outcomes. We review the hypotheses for these noninferiority and equivalence research questions, consider power and sample size issues, and discuss how to perform such a test for both binary and survival outcomes. The methods are illustrated on 2 recent studies in hematopoietic cell transplantation.

Chlorella vulgaris up-modulation of myelossupression induced by lead: The role of stromal cells

In this study, Chlorella vulgaris (CV) was examined for its chelating effects on the ability of bone marrow stromal cell layer to display myeloid progenitor cells in vitro in lead-exposed mice, using the long-term bone marrow culture (LTBMC). In addition, the levels of interleukin (IL)-6, an important hematopoietic stimulator, as well as the numbers of adherent and non-adherent cells were also investigated. Mice were gavage treated daily with a single 50 mg/kg dose of CV for 10 days, concomitant to continuous offering of 1300 ppm lead acetate in drinking water. We found that CV up-modulates the reduced ability of stromal cell layer to display myeloid progenitor cells in vitro in lead-exposed mice and restores both the reduced number of non-adherent cells and the ability of stromal cells from these mice to produce IL-6. Monitoring of lead poisoning demonstrated that CV treatment significantly reduced lead levels in blood and tissues, completely restored the normal hepatic ALA levels, decreased the abnormally high plasma ALA and partly recovered the liver capacity to produce porphyrins. These findings provide evidence for a beneficial use of CV for combination or alternative chelating therapy to protect the host from the damage induced by lead poisoning. (C) 2008 Elsevier Ltd. All rights reserved.

Detailed molecular characterization of cord blood-derived endothelial progenitors

Objective. Given their involvement in pathological and physiological angiogenesis, there has been growing interest in understanding and manipulating endothellial progenitor cells (EPC) for therapeutic purposes. However, detailed molecular analysis of EPC before and during endothelial differentiation is lacking and is the subject of the present study. Materials and Methods. We report a detailed microarray gene-expression profile of freshly isolated (day 0) human cord blood (CB)-derived EPC (CD133(+)KDR(+) or CD34(+)KDR(+)), and at different time points during in vitro differentiation (early: day 13; late: day 27). Results. Data obtained reflect an EPC transcriptome enriched in genes related to stem/progenitor cells properties (chromatin remodeling, self-renewal, signaling, cytoskeleton organization and biogenesis, recruitment, and adhesion). Using a complementary DNA microarray enriched in intronic transcribed sequences, we observed, as well, that naturally transcribed intronic noncoding RNAs were specifically expressed at the EPC stage. Conclusion. Taken together, we have defined the global gene-expression profile of CB-derived EPC during the process of endothelial differentiation, which can be used to identify genes involved in different vascular pathologies. (C) 2008 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.

Omslagstrender - en studie av vad som höjer uppmärksamhetsvärdet hos tidskrifter

Through interviews, a questionnaire survey and an in­depth analysis of the Swedish magazines Veckorevyn and Magazine Café has a number of parameters been made visible. It was difficult to obtain an unambiguous result when the journal's target audience is crucial for the cover design. Nevertheless, we can generally say that the transparent varnish of covers, PMS colors and enclosing the journal in plastic do not increase the attention value, as this occurs in many magazines. Due to today's tough competition among journals, we believe that they will need to niche themselves much harder to survive. We also believe that the new, big trend is that more covers will become more plain and stylistically pure, with one big communicating image and fewer coverlines, as many covers were designed during the 1940s.

The Survivability of Swedish Emergency Management Related Research Centers and Academic Programs : A Preliminary Sociology of Science Analysis

The Survivability of Swedish Emergency Management Related Research Centers and Academic Programs: A Preliminary Sociology of Science Analysis Despite being a relatively safe nation, Sweden has four different universities supporting four emergency management research centers and an equal and growing number of academic programs. In this paper, I discuss how these centers and programs survive within the current organizational environment. The sociology of science or the sociology of scientific knowledge perspectives should provide a theoretical guide. Yet, scholars of these perspectives have produced no research on these related topics. Thus, the population ecology model and the notion of organizational niche provide my theoretical foundation. My data come from 26 interviews from those four institutions, the gathering of documents, and observations. I found that each institution has found its own niche with little or no competition – with one exception. Three of the universities do have an international focus. Yet, their foci have minimal overlap. Finally, I suggest that key aspects of Swedish culture, including safety, and a need aid to the poor, help explain the extensive funding these centers and programs receive to survive. 

Organisationer, ojämlikhet, migration : förändringar av den etniska arbetsdelningen i svensk byggnadssektor

Organizations, Inequality, Migration – Changes of the Ethnic Division of Labour in the Swedish Construction Sector During the 1990s the number of migrants from Eastern Europe increased in the Swedish construction sector. This article examines how this change was initiated by changes in the organizational population in the construction sector. The gradual enlargement of the European Union changed the institutional framework for organizations in Sweden. This created increased opportunities for new organizational forms in the construction sector. The specific niche of the new organizations was to recruit and hire out workers from Eastern Europe that were paid lower wages than Swedish workers. The diffusion of this organizational form contributed to a change of norms and beliefs about what was legitimate and illegitimate when employing migrants. This implies that the inequalities that this organizational form introduces have gained increased legitimacy in Sweden. Or in other words, it has become increasingly socially acceptable to pay migrants lower wages than Swedish workers

A espetacularização do crime violento pela televisão : o caso do programa Linha Direta

Esta dissertação analisa a espetacularização da criminalidade violenta operada pela televisão, buscando compreender como o jornalismo televisivo representa e produz a questão da criminalidade violenta no Brasil, tendo como referencial empírico o programa Linha Direta da Rede Globo de Televisão. Para analisar textos e imagens em movimento foi utilizada uma combinação de técnicas de pesquisa apoiada nos recentes e poderosos recursos das metodologias informacionais aplicadas à pesquisa qualitativa, mais especificamente o software NVivo. A investigação de uma amostra de programas gravados, relativa aos seis primeiros meses de exibição, permitiu constatar que o Linha Direta leva às últimas conseqüências a tendência do campo jornalístico em misturar jornalismo e ficção, ou seja, recursos da reportagem tradicional e dramaturgia, a partir da reconstrução dos casos criminais com atores. Embora o discurso do programa aponte para uma atuação alinhada com a realização da justiça frente à situação da criminalidade violenta – pelo oferecimento de uma forma de participação do espectador na resolução dos casos –, os elementos narrativos disponibilizados nas reconstruções dos crimes proporcionam a reprodução simbólica do sentimento coletivo de insegurança e impunidade e o reforço da percepção sobre a ineficácia da polícia e da justiça. A partir da exploração dramática e espetacular de imagens de dor, o programa busca legitimação para agir, não apenas como um colaborador das agências formais de controle, mas como um reinventor cultural das práticas jurídicas e de controle social, relativizando, em proveito próprio, os papéis das delegacias e tribunais na sociedade.