Immune cells and oxidative stress in the endotoxin tolerance mouse model

Sepsis is a systemic inflammatory response that can lead to tissue damage and death. In order to increase our understanding of sepsis, experimental models are needed that produce relevant immune and inflammatory responses during a septic event. We describe a lipopolysaccharide tolerance mouse model to characterize the cellular and molecular alterations of immune cells during sepsis. The model presents a typical lipopolysaccharide tolerance pattern in which tolerance is related to decreased production and secretion of cytokines after a subsequent exposure to a lethal dose of lipopolysaccharide. The initial lipopolysaccharide exposure also altered the expression patterns of cytokines and was followed by an 8- and a 1.5-fold increase in the T helper 1 and 2 cell subpopulations. Behavioral data indicate a decrease in spontaneous activity and an increase in body temperature following exposure to lipopolysaccharide. In contrast, tolerant animals maintained production of reactive oxygen species and nitric oxide when terminally challenged by cecal ligation and puncture (CLP). Survival study after CLP showed protection in tolerant compared to naive animals. Spleen mass increased in tolerant animals followed by increases of B lymphocytes and subpopulation Th1 cells. An increase in the number of stem cells was found in spleen and bone marrow. We also showed that administration of spleen or bone marrow cells from tolerant to naive animals transfers the acquired resistance status. In conclusion, lipopolysaccharide tolerance is a natural reprogramming of the immune system that increases the number of immune cells, particularly T helper 1 cells, and does not reduce oxidative stress.FAPESPCNP

Urban–rural differences of gynaecological malignancies in Egypt (1999–2002)

Please cite this paper as: Dey S, Hablas A, Seifeldin I, Ismail K, Ramadan M, El-Hamzawy H, Wilson M, Banerjee M, Boffetta P, Harford J, Merajver S, Soliman A. Urban–rural differences of gynaecological malignancies in Egypt (1999–2002). BJOG 2010;117:348–355.In previous studies, we have shown a three to four times higher urban incidence of breast cancer and estrogen receptor-positive breast cancers in the Gharbiah Province of Egypt. We investigated the urban–rural incidence differences of gynaecologic malignancies (uterine, ovarian and cervical cancers) to explore if they show the same trend that we found for breast cancer.Cancer registry-based incidence comparison.Gharbiah population-based cancer registry (GPCR), Tanta, Egypt.All patients with uterine, ovarian and cervical cancer in GPCR from 1999 to 2002.We calculated uterine, ovarian and cervical cancer incidence from 1999 to 2002. For each of the three cancers, we calculated the overall and age-specific rates for the province as a whole, and by urban–rural status, as well as for the eight districts of the province.Incidence of all three cancer sites was higher in urban than in rural areas. Uterine cancer showed the highest urban–rural incidence rate ratio (IRR = 6.07, 95% CI = 4.17, 8.85). Uterine cancer also showed the highest urban incidence in the oldest age group (70+ age category, IRR = 14.39, 95% CI = 4.24, 48.87) and in developed districts (Tanta, IRR = 4.14, 95% CI = 0.41, 42.04). Incidence rates by groups of cancer sites showed an increasing gradient of urban incidence for cancers related to hormonal aetiology, mainly of the breast and uterus (IRR = 4.96, 95% CI = 2.86, 8.61).The higher urban incidence of uterine cancer, coupled with our previous findings of higher incidence of breast cancer and estrogen receptor positive breast cancer in urban areas in this region, may be suggestive of possible higher exposure to environmental estrogenic compounds, such as xenoestrogens, in urban areas.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78726/1/j.1471-0528.2009.02447.x.pd

Política industrial na Rússia: observações sobre o desenvolvimento do setor de Tecnologia da Informação entre 2000 e 2008

A pesquisa analisa o desenvolvimento do setor de tecnologia da informação na Rússia. O principal objetivo do trabalho é a análise, através de discursos, produção de projetos governamentais e legislação relativa ao tema, para identificar a existência de uma política de desenvolvimento para a tecnologia da informação e entender qual seu intuito durante os primeiros dois governos de Vladimir Putin (2000 - 2004 e 2004 - 2008). Apoiando-se em uma exposição breve sobre a nova dinâmica mundial em relação às tecnologias da informação e os anos de desestabilização econômica e política da década de 1990, busca abordar os momentos chave para a consolidação dessa área científica. Além disso, se busca uma lógica de Estado em relação à tecnologia da informação que seria a responsável pela formação de uma política industrial para o setor.The research analyzes the development of the information technology sector in Russia. The main objective of the work is the analysis, through speeches, production of government projects and legislation on the subject, identify the existence of a development policy for information technology and understand its purpose during the first two Vladimir Putin’s governments (2000 - 2004 and 2004 - 2008). Based on a brief exposition on the new global dynamics in information technologies and the years of economic and political destabilization of the 1990s, it seeks to address the key moments for the consolidation of this scientific area in the country. Furthermore, a State logic is sought in relation to information technology, which would be responsible for the formation of an industrial policy for the sector

Xenoestrogênios : o exemplo do bisfenol-a

Evidências acumuladas indicam que a saúde dos seres humanos, animais e espécies selvagens pode sofrer conseqüências adversas da exposição a produtos químicos presentes no meio ambiente e que interagem com o sistema endócrino, tais como bifenilas policloradas, dioxinas, estrogênios de ocorrência natural e sintéticos. Por outro lado, permanecem incertezas científicas com respeito aos dados relatados e, também, quanto à hipótese de haver níveis suficientemente elevados de exposição a estes agentes, a ponto de exercer efeito estrogênico generalizado sobre a população. Este trabalho revisa os principais tópicos relacionados a um dos xenoestrogênios que vem sendo mais recentemente estudado: o Bisfenol A (BFA), um monômero de plástico policarbonato, com pouca homologia estrutural com o estradiol (E2) mas semelhante ao dietilestilbestrol (DES), hexestriol e componente bisfenólico do tamoxifeno. O presente trabalho comenta e analisa criticamente os efeitos do BFA sobre o trato reprodutivo e função lactotrófica em animais de experimentação, à luz das informações disponíveis e experiência do grupo nesta área, e recomenda algumas necessidades de pesquisa.Some evidences indicate that humans and domestic and wildlife species might suffer adverse consequences from exposure to environmental chemicals that interact with the endocrine system, including polychlorinated biphenyls, dioxins, synthetic and naturally occurring plant estrogens. However, considerable scientific uncertainty remains regarding the causes of these reported effects and whether sufficiently high levels of endocrine-disrupting chemicals exist in the ambient environment to exert adverse effects on the general population. This review summarizes the principal issues related to bisphenol A, an environmental endocrine disrupting chemical with estrogen activity. Bisphenol A is a monomer of plastics and has little structural homology with estradiol, sharing similarity with synthetic estrogens such as diethylstilbestrol and with the bisphenolic component of tamoxifen. In the light of available information and our laboratory experience in this field of research, this work comments and critically analyses the effects of BPA on the reproductive tract and lactotroph function in several rat strains, and also offers some recommendations for additional research

Xenoestrogênios : o exemplo do bisfenol-a

Evidências acumuladas indicam que a saúde dos seres humanos, animais e espécies selvagens pode sofrer conseqüências adversas da exposição a produtos químicos presentes no meio ambiente e que interagem com o sistema endócrino, tais como bifenilas policloradas, dioxinas, estrogênios de ocorrência natural e sintéticos. Por outro lado, permanecem incertezas científicas com respeito aos dados relatados e, também, quanto à hipótese de haver níveis suficientemente elevados de exposição a estes agentes, a ponto de exercer efeito estrogênico generalizado sobre a população. Este trabalho revisa os principais tópicos relacionados a um dos xenoestrogênios que vem sendo mais recentemente estudado: o Bisfenol A (BFA), um monômero de plástico policarbonato, com pouca homologia estrutural com o estradiol (E2) mas semelhante ao dietilestilbestrol (DES), hexestriol e componente bisfenólico do tamoxifeno. O presente trabalho comenta e analisa criticamente os efeitos do BFA sobre o trato reprodutivo e função lactotrófica em animais de experimentação, à luz das informações disponíveis e experiência do grupo nesta área, e recomenda algumas necessidades de pesquisa.Some evidences indicate that humans and domestic and wildlife species might suffer adverse consequences from exposure to environmental chemicals that interact with the endocrine system, including polychlorinated biphenyls, dioxins, synthetic and naturally occurring plant estrogens. However, considerable scientific uncertainty remains regarding the causes of these reported effects and whether sufficiently high levels of endocrine-disrupting chemicals exist in the ambient environment to exert adverse effects on the general population. This review summarizes the principal issues related to bisphenol A, an environmental endocrine disrupting chemical with estrogen activity. Bisphenol A is a monomer of plastics and has little structural homology with estradiol, sharing similarity with synthetic estrogens such as diethylstilbestrol and with the bisphenolic component of tamoxifen. In the light of available information and our laboratory experience in this field of research, this work comments and critically analyses the effects of BPA on the reproductive tract and lactotroph function in several rat strains, and also offers some recommendations for additional research

Indução da maturação sexual em ratas wistar pelo xenoestrogênio bisfenol A

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Indução da maturação sexual em ratas wistar pelo xenoestrogênio bisfenol A

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Endotoxin tolerance: Selective alterations in gene expression and protection against lymphocyte death

Extensive lymphocyte apoptosis may be an important cause of immune suppression in sepsis. Here we investigated the effect of LPS tolerance on lymphocyte apoptosis in an experimental model of polymicrobial infection. Tolerance was induced by the injection of lipopolysaccharide (1.0 mg/kg/subcutaneously) once a day for 5 days. Macroarray analysis of mRNA isolated from T-(CD4) lymphocytes was used to identify genes that are differentially expressed during LPS tolerance. In addition, assessment of the expression of apoptosis-associated lymphocyte gene products and apoptotic events was performed on the 8th day; 6 h after the terminal challenge with polymicrobial infection or high-dose LPS administration. Survival studies with polymicrobial infection were also conducted. LPS tolerance induced a broad reprogramming of cell death pathways, including a suppression of receptor-mediated and mitochondrial apoptotic pathways, inflammatory caspases, alternate apoptotic pathways, as well as reduced expression of genes involved in necrosis. These alterations led to a marked resistance of lymphocytes against cell death during the subsequent period of sepsis. In addition, LPS tolerance produced an increased differentiation of T-lymphocytes to T(H)1 and T(H)2, with a T(H)1 differentiation predominance. Thus, in the current study we provide an evidence for a marked reprogramming of gene expression of multiple cell death pathways during LPS tolerance. These alterations may play a significant role in the observed protection of the animals from a subsequent lethal polymicrobial sepsis challenge. (C) 2009 Elsevier GmbH. All rights reserved.National Institutes of Health (NIH)[R01GM060915][FAPESP-02/07430-6][CNPq-470744/2004-9