Influência do Estresse Agudo de Restrição sobre Processo Inflamatório Induzido pela Carragenina

O estresse é um fator ambiental que altera respostas fisiológicas envolvendo a liberação de corticóides e catecolaminas. Os glicocorticóides afetam o sistema imune. O objetivo deste trabalho é avaliar o efeito do estresse agudo sobre o processo inflamatório em ratos estressados submetidos à  2h de restrição e controles. Após o estresse, foi realizado o modelo de pleurisia induzida pela carragenina. Os resultados demonstraram diferença nos leucócitos totais antes e depois da pleurisia apenas no grupo controle. Na contagem diferencial de leucócitos circulantes, foram encontradas diferenças no percentual de linfócitos e neutrófilos entre os grupos antes da indução do processo inflamatório. No exsudato pleural não foram encontradas diferenças no total de leucócitos e na análise nas células polimorfo e mononucleares em ambos os grupos. Os resultados sugerem que no estresse agudo, após imediata realização da pleurisia ocorrem alterações imunológicas que parecem não influenciar o processo inflamatório agudo

Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950-2019 : a comprehensive demographic analysis for the Global Burden of Disease Study 2019

Background: Accurate and up-to-date assessment of demographic metrics is crucial for understanding a wide range of social, economic, and public health issues that affect populations worldwide. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 produced updated and comprehensive demographic assessments of the key indicators of fertility, mortality, migration, and population for 204 countries and territories and selected subnational locations from 1950 to 2019. Methods: 8078 country-years of vital registration and sample registration data, 938 surveys, 349 censuses, and 238 other sources were identified and used to estimate age-specific fertility. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate age-specific fertility rates for 5-year age groups between ages 15 and 49 years. With extensions to age groups 10–14 and 50–54 years, the total fertility rate (TFR) was then aggregated using the estimated age-specific fertility between ages 10 and 54 years. 7417 sources were used for under-5 mortality estimation and 7355 for adult mortality. ST-GPR was used to synthesise data sources after correction for known biases. Adult mortality was measured as the probability of death between ages 15 and 60 years based on vital registration, sample registration, and sibling histories, and was also estimated using ST-GPR. HIV-free life tables were then estimated using estimates of under-5 and adult mortality rates using a relational model life table system created for GBD, which closely tracks observed age-specific mortality rates from complete vital registration when available. Independent estimates of HIV-specific mortality generated by an epidemiological analysis of HIV prevalence surveys and antenatal clinic serosurveillance and other sources were incorporated into the estimates in countries with large epidemics. Annual and single-year age estimates of net migration and population for each country and territory were generated using a Bayesian hierarchical cohort component model that analysed estimated age-specific fertility and mortality rates along with 1250 censuses and 747 population registry years. We classified location-years into seven categories on the basis of the natural rate of increase in population (calculated by subtracting the crude death rate from the crude birth rate) and the net migration rate. We computed healthy life expectancy (HALE) using years lived with disability (YLDs) per capita, life tables, and standard demographic methods. Uncertainty was propagated throughout the demographic estimation process, including fertility, mortality, and population, with 1000 draw-level estimates produced for each metric. Findings: The global TFR decreased from 2·72 (95% uncertainty interval [UI] 2·66–2·79) in 2000 to 2·31 (2·17–2·46) in 2019. Global annual livebirths increased from 134·5 million (131·5–137·8) in 2000 to a peak of 139·6 million (133·0–146·9) in 2016. Global livebirths then declined to 135·3 million (127·2–144·1) in 2019. Of the 204 countries and territories included in this study, in 2019, 102 had a TFR lower than 2·1, which is considered a good approximation of replacement-level fertility. All countries in sub-Saharan Africa had TFRs above replacement level in 2019 and accounted for 27·1% (95% UI 26·4–27·8) of global livebirths. Global life expectancy at birth increased from 67·2 years (95% UI 66·8–67·6) in 2000 to 73·5 years (72·8–74·3) in 2019. The total number of deaths increased from 50·7 million (49·5–51·9) in 2000 to 56·5 million (53·7–59·2) in 2019. Under-5 deaths declined from 9·6 million (9·1–10·3) in 2000 to 5·0 million (4·3–6·0) in 2019. Global population increased by 25·7%, from 6·2 billion (6·0–6·3) in 2000 to 7·7 billion (7·5–8·0) in 2019. In 2019, 34 countries had negative natural rates of increase; in 17 of these, the population declined because immigration was not sufficient to counteract the negative rate of decline. Globally, HALE increased from 58·6 years (56·1–60·8) in 2000 to 63·5 years (60·8–66·1) in 2019. HALE increased in 202 of 204 countries and territories between 2000 and 2019

Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

Effects of prenatal stress on the lymphocytes mice litter activity

Sabe-se que o feto é vulnerável a modificações do millieu materno, especificamente, a exposição a um estressor ativa sistemas neuroendócrinos (expoentes o eixo hipotálamo-hipófise-adrenais HPA e o sistema nervoso autônomo simpático SNAS). Quando no terço final da gestação, essas mudanças podem interferir com o desenvolvimento/ maturação neuroimune. Estudos prévios de nosso grupo demonstraram que, o estresse pré-natal diminuiu significativamente a imunidade inata e aumentou o turnover de noradrenalina hipotalâmica de camundongos, dados que somados a outros de literatura levaram aos objetivos deste trabalho: analisar os efeitos de um estresse pré-natal sobre parâmetros de linfócitos de camundongos. Os resultados obtidos mostraram que a aplicação de choques nas patas (0,2 mA, 10 choques/sessão), tanto no terço final gestacional quanto após desafio agudo pós-natal, contudo, não modificou significativamente os parâmetros linfocitários avaliados. Baseado nisto, levantamos hipóteses: 1- a existência de vias de redundância fisiológica capacitaria o organismo a manter sua homeostasia frente aos estressores empregados; 2- inaptidão do modelo de estresse empregado; 3- ausência de desafio imune prévio à análise de um sistema que é responsivo (adaptativo). A primeira hipótese confirmou-se quando desenvolvemos como estresse pós-natal o modelo do estresse do metrô de Nova Iorque; a segunda hipótese confirmou-se também verdadeira através de desafio em modelo experimental de a asma OVA-induzida; finalmente, a terceira hipótese foi confirmada por estudos de outros autores.As a consequence of his fast development, the fetus is vulnerable to modifications from the hormonal maternal millieu. This is explained mainly by the permeability of the placentary barrier to several hormones and substances. Specifically, it is known that the maternal exposition to a stressor activates neuroendocrine systems (exponents, the hypothalamus-pituitary-adrenal axis HPA, and the sympathetic autonomic nervous system SANS), causing an exaggerated production of neuropeptides, which have the potential to change the motherly-fetus homeostasis. When this unbalance occurs in the final three months of pregnancy, it may impact fetal systems that are still being developed/matured, as the immune and nervous systems. According to previous studies, the prenatal-stress proposed in this work was able to produce a significant decrease on innate immunity as assessed by the evaluation of the activity of peritoneal macrophages; it was also, a significant increment in hypothalamic noradrenaline turnover. Such prenatal events, could be derived and/or reflect a lost in adaptative immunity homeostasis. The objective of this work was, thus, to analyze lymphocyte parameters of prenatal stressed mice. A footshock stress (0,2 mA, 10 shocks of 5 seconds each/session) was applied both in the final third of gestation and/or in the postnatal adult life. Those stressors was anable to affect the lymphocytes viability and their subpopulation patterns token from peripheral blood; the esplenic lymphocytes proliferation ratio were also not changed. Those results suggested that: 1- the stress model was not effective; 2- the obtained results reflected the absence of an immune challenge applied previous by the experiments performedb; 3- the existence of physiologic redundancies turns the organisms able to react in a homeostatic way even exposed to stress situations

Effect of prenatal stress in regulating pulmonary allergic inflammation in a murine model of experimental asthma

Devido ao seu rápido crescimento, o feto é particularmente vulnerável a insultos e modificações no millieu hormonal. Este fato sugere que situações adversas experimentadas pela mãe grávida podem alterar o desenvolvimento e a saúde da prole, explicado principalmente pela permeabilidade da barreira placentária a diversos hormônios e substâncias. O objetivo deste trabalho foi estudar o efeito do estresse pré-natal na regulação da inflamação alérgica pulmonar, empregando o modelo murino de asma experimental. Para este propósito foram utilizadas camundongas virgens da linhagem Swiss, com 50 dias de idade. Foi empregado o modelo de choque nas patas para promover o estresse pré-natal e o modelo do “metrô de Nova Efeito do estresse pré-natal na regulação da inflamação alérgica pulmonar no modelo murino de asma experimental 65 Iorque” para o estresse pós-natal. As fêmeas foram distribuídas em 4 grupos experimentais: CC: fêmeas não estressadas;CE: fêmeas estressadas pós-natalmente aos 60 dias de idade (PND60), EC: fêmeas nascidas de mães estressadas entre o dia 15 (GD15) e 18 de gestação (GD18); EE: fêmeas nascidas de mães estressadas entre o GD15 e GD18 e estressadas pós-natalmente aos PND60. A indução da inflamação alérgica pulmonar foi realizada através da sensibilização dos animais com solução de ovalbumina (OVA) 0,1 mg.Kg-1 sc para avaliação do leucograma, lavado broncoalveolar (BAL), celularidade hematopoiética medular e neuroquímica. Os experimentos foram realizados 24h após a última sessão de nebulização.O número de células do BAL foi significantemente maior nos animais do grupo EE, em relação àqueles dos grupos CC (P<0.01), CE (P<0.01) e EC (P<0.001). Na contagem diferencial do BAL os linfócitos e macrófagos do grupo EE foram significantemente maiores que em os outros grupos avaliados (P<0.05). Na contagem diferencial de células no sangue não foram observadas alterações (P>0.05) para os linfócitos, neutrófilos, eosinófilos e monócitos; porém, observou-se diferenças significativas (P<0.05) entre o número de bastonetes dos grupos, sendo maior nos animais do grupo CC em relação àquelesdo grupo EC. O número de células hematopoiéticas da medula óssea foi significantemente (P<0.05) menor nos animais do grupo EE, em relação àqueles do grupo CC. No córtex pré-frontal, há diferenças significantes na relação Ácido Homovanílico/Dopamina (HVA/DA) (P<0.05), sendo maior nos animais do grupo EC, em relação àqueles do grupo CE. Em conclusão,o estresse pré-natal levou a modulação de células do sistema imune (SI) dos neonatos, evidenciado após a exposição a estresse agudo pós-natal, amplificando a resposta alérgica pulmonar. Sugere-se que a maior susceptibilidade dos animais do grupo EE seja consequência de alterações induzidas pelo estresse pré-natal no eixo hipotálamo-pituitária-adrenal (HPA).Due to the rapid growth of the fetus it is particularly vulnerable to insults and changes in hormonal milieu. Therefore, is suggested that adverse situations experienced by the pregnant mother can alter the development and health of offspring, mainly due to the permeability of the placental barrier to various hormones and substances. The aim of the present investigation was to study the effects of prenatal stress in the regulation of pulmonary allergic inflammation, employing the murine model of experimental asthma. For this purpose, were used virgin female mice, Swiss lineage, of 50 days old. The models used were foot shock to induce prenatally stress, and "New York subway" stress to induce postnatally stress. Females were divided into 4 groups: CC group: not stressed females; CE group: postnatally stressed females (PND60); EC: females born from stressed mothers (GD15 to GD18); EE Group: females born from stressed mothers (GD15 to GD18) (footshock) and postnatally stressed (PND60). The induction of allergic pulmonary inflammation was done through sensitization of animals with 0,1 mg.Kg-1 sc of ovalbumin (OVA) solution, to further evaluate leukogram, bronchoalveolar lavage (BAL) hematopoietic marrow cellularity and neurochemistry. The experiments were performed 24 hours after the last session of nebulization. The number of BAL cells was significantly higher in EE group animals compared with the CC group (P<0.01), CE (P<0.01) and CE (P<0.001). In the differential count of the BAL, lymphocytes and macrophages of EE group were significantly higher than the other groups studied (P<0.05). In the blood differential cell count were not observed changes (P>0.05) for lymphocytes, neutrophils, eosinophils and monocytes; however, there were significant differences (P<0.05) observed in the number of rods cells between groups, being higher in animals the CC group compared to EC group. The number of hematopoietic cells of the bone marrow was significantly lower (P<0.05) in animals of Group EE, compared with CC group. In the prefrontal cortex, there were significant differences in homovanillic acid /dopamine (HVA/DA) (P<0.05) rate, being higher in the EC group, compared to EC group. In conclusion, prenatal stress modulated the immune system (SI) cells of neonates, evidenced after exposure to a post-natal acute stress by amplification of pulmonary allergic response. It is suggested that the increased susceptibility of animals EE group is a result of changes induced by prenatal stress on hypothalamus pituitary-adrenal (HPA) axis