In Vivo Role of Neutrophil Extracellular Traps in Antiphospholipid Antibody–Mediated Venous Thrombosis

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136296/1/art39938_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136296/2/art39938.pd

Ectonucleotidase-Mediated Suppression of Lupus Autoimmunity and Vascular Dysfunction

ObjectivesCD39 and CD73 are surface enzymes that jut into the extracellular space where they mediate the step-wise phosphohydrolysis of the autocrine and paracrine danger signals ATP and ADP into anti-inflammatory adenosine. Given the role of vascular and immune cells’ “purinergic halo” in maintaining homeostasis, we hypothesized that the ectonucleotidases CD39 and CD73 might play a protective role in lupus.MethodsLupus was modeled by intraperitoneal administration of pristane to three groups of mice: wild-type (WT), CD39−/−, and CD73−/−. After 36 weeks, autoantibodies, endothelial function, kidney disease, splenocyte activation/polarization, and neutrophil activation were characterized.ResultsAs compared with WT mice, CD39−/− mice developed exaggerated splenomegaly in response to pristane, while both groups of ectonucleotidase-deficient mice demonstrated heightened anti-ribonucleoprotein production. The administration of pristane to WT mice triggered only subtle dysfunction of the arterial endothelium; however, both CD39−/− and CD73−/− mice demonstrated striking endothelial dysfunction following induction of lupus, which could be reversed by superoxide dismutase. Activated B cells and plasma cells were expanded in CD73−/− mice, while deficiency of either ectonucleotidase led to expansion of TH17 cells. CD39−/− and CD73−/− mice demonstrated exaggerated neutrophil extracellular trap release, while CD73−/− mice additionally had higher levels of plasma cell-free DNA.ConclusionThese data are the first to link ectonucleotidases with lupus autoimmunity and vascular disease. New therapeutic strategies may harness purinergic nucleotide dissipation or signaling to limit the damage inflicted upon organs and blood vessels by lupus

Tendência da mortalidade por doenças neoplásicas em 10 capitais brasileiras, de 1980 a 2000 Cancer mortality trends in 10 Brazilian capitals, 1980 - 2000

O objetivo deste estudo foi analisar a tendência da mortalidade por doenças neoplásicas, segundo sexo e faixa etária, no período de 1980 a 2000, em 10 capitais brasileiras. Para tanto, realizou-se um estudo ecológico de série temporal, utilizando dados de óbitos de indivíduos acima de 30 anos de ambos os sexos. Os dados de mortalidade foram obtidos do Sistema de Informação sobre Mortalidade do Ministério da Saúde (SIM/MS/DATASUS). Utilizou-se a padronização dos coeficientes de mortalidade pelo método direto e o método de regressão linear simples. O coeficiente médio padronizado de mortalidade por neoplasia, estimado entre 1980 e 2000, foi de 10.239 mortes, com aumento de 5.220 mortes por 100 mil habitantes ao ano. Os coeficientes de mortalidade foram maiores no sexo masculino e indivíduos acima de 60 anos. Observou-se tendência crescente da mortalidade nas capitais analisadas, em ambos os grupos etários, sendo maior nas capitais das regiões Centro-Oeste, Norte e Nordeste e na população acima de 60 anos. A elevada mortalidade para o sexo masculino e a população idosa deve-se, provavelmente, à maior exposição aos fatores de risco ambientais e à maior prevalência de cânceres letais entre os homens. As capitais das regiões Sul e Sudeste seguem tendência crescente, porém com incremento menor comparado às demais, provavelmente devido aos maiores avanços no processo de transição demográfica e epidemiológica, e melhores serviços de assistência médica. Este estudo mostrou que a mortalidade por neoplasia aumentou ao longo da série temporal, podendo se tornar a principal causa de morte no Brasil.<br>The objective of this study was to analyze the cancer mortality trends, according to gender and age, in the period from 1980 to 2000, in ten Brazilian capitals. To that end, an ecological time series study was carried out, using mortality data of subjects above 30 years of age and of both genders. Mortality data were obtained from the Mortality Information System of the Ministry of Health (SIM/MS/DATASUS). Mortality rates were standardized by the direct method and the simple linear regression method. The average standardized mortality rate for cancer, estimated between 1980 and 2000, was 10,239 deaths, with an increase of 5,220 deaths per 100,000 inhabitants for each year. Mortality rates were higher in men and individuals above 60 years of age. A growing trend in mortality was observed in the capitals analyzed, in both age groups, and was higher in the capitals of the North, Northwest and Center-West regions and in the population above 60 years of age. The high mortality for men and the elderly population was probably due to the higher exposure to environmental risk factors and greater prevalence of lethal cancers among men. The capitals of the South and Southeast regions followed the growing trend, with a smaller increase in comparison to the others, due to the largest advances in the demographic and epidemiologic transition process and better health care. This study showed that the mortality due to cancer has increased in the time series, and may possibly become the major cause of death in Brazil