ABSTRACT
Introduction: Orosomucoid also named Alpha-1 Acid Glycoprotein(AGP) is a major acute-phase protein and is increased in response to systemic injury and inflammation. AGP has been described as an inhibitor of neutrophil migration on sepsis, particularly its immunomodulation effects. The AGP biological functions are not understood in Coronavirus disease 2019 (COVID-19). Hypothesis: We hypothesize that plasmatic AGP is upregulated in severe Covid-19 patients and is involved in the regulation of netosis. Therefore, we sought to investigate the role of AGP in plasmatic from COVID-19 severe infection patients and neutrophils infected with Severe Acute Respiratory Syndrome Coronavirus-2 (SarsCov-2). Method(s): Epidemiological data and AGP, interleukin-6 (IL-6), C-reactive protein (PCR), lactate, and other laboratorial parameters were measured in blood samples from 52 subjects hospitalized in the ICU with clinically SarsCov-2 infection confirmed by RT-PCR. To evaluate the role of AGP in netosis in neutrophils, blood samples from health patients (n=13) were collected, and neutrophils were separated and infected with Sars-Cov-2 (Moi=1). Those neutrophils were treated with AGP (10mug/ml) or vehicle for 18 hours and netosis was analyzed by flow cytometry (n=10) and immunofluorescence (IF;n=10). Early and late netosis, respectively, were characterized by negative or positive FVS and positive Sytox. The neutrophil extracellular traps (NETs) were investigated by myeloperoxidase (MPO), neutrophil elastase (NE), and DAPI by IF and quantified Netquant/Matlab software. This study was approved by Ethics Committee -CAAE: 30816620.0.0000.5440. Result(s): AGP increased in severe Covid-19 patients (p<0.05). A positive correlation between AGP with IL-6 and C-reactive protein (respectively, p=0.005, p=0.002) and a negative correlation between AGP and lactate (p=0.004) were found it. Together, AGP treatment downregulated early (35,7%) and late (43,5%) netosis in neutrophils infected with SarsCov-2. Confocal analysis by MPO, NE e DAPI showed NETs released by neutrophils infected with Sar-Cov-2 decreased when neutrophils were treated with AGP (p<0.05). Conclusion(s): Our data showed increased AGP in COVID-19 infection and contributed to netosis regulation.
ABSTRACT
The Amazon, as it becomes the scene for sacrifices that serve to solidify economic-political agreements, is the object of an asymmetric war due to new appropriations and capitalization. Our purpose was to demonstrate how the different fronts of dispossession in the Amazon Region advance and intertwine so that the practices of stigmatization and extermination that drive them are made explicit. Our objective was to map the new arc of deforestation in the Amazon, identifying a set of threats to the Conservation Corridor of the State of Rondônia and the border region with Bolivia, more specifically the region comprising the Guajará-Mirim State Park, the Jaci Paraná Extractive Reserve, and the Indigenous Lands Karipuna, Igarapé Ribeirão, Igarapé Lage. These are Conservation Units and Indigenous Territories severely affected by timber, mineral, and agricultural activities on both sides of the border. The Amazon Region has served to deepen the neo-extractive productive profile of Brazil and the Latin American continent, a profile that increasingly depends on the flexibility of territorial rights and the precariousness of the workforce. This regime of territorial simplification and political reduction comprises a) regulatory frameworks at the request of investors;b) discursive formations for the opening of borders against any environmental limit or social agreement;c) militarization (and paramilitarization) of territories in the process of appropriation. We elaborated social cartographies that provided a spatial understanding of the business strategies that converge for this region. In response to these strategies, we observed resistance processes in a context of “duplicate risk” to which indigenous and original peoples are subjected, considering the perversely different effects of the COVID-19 pandemic on them. © 2022 Universidade Federal do Parana. All rights reserved.
ABSTRACT
Objective: The pathophysiological mechanism of acute lung injury in COVID-19 includes a cascade of local and systemic responses with activation of several proinflammatory cytokines, including metalloproteinases. The aim of this study is investigate the role of matrix metalloproteinase-9 (MMP-9) in plasma from patients with severe COVID-19 hospitalized in a Brazilian ICU Design and method: The study was designed to analyze the MMP-9 plasmatic in COVID-19 severe infection. Epidemiological data and blood samples were obtained from 42 subjects hospitalized in the ICU with clinically SARS-CoV-2 infection con firmed by RT-PCR (COVID), and 15 healthy subjects (Control). Zymography methods obtained the MMP-9 plasma activity. Continuous variables are shown by mean±STDV and analyzed by the Mann-Whitney test. Categorical variables were compared by the Chi-squared test. The MMMP-9 activity is shown in the log of normalized and analyzed by unpaired T-test. Two-way ANOVA was used to analyze subgroups divided by gender, age greater or less than the median 60.4-year-old, hypertensive or normotensive, non-obese or obese Results: The COVID and Control groups did not differ signi ficantly by age (62.6±13vs.57.6±12.2 years old, p=0.097) and BMI (30.3±6.1vs.29.33±5.7 kg/m2, p=0.338). The COVID group has fewer women than the Control group (28.6%vs.80%, p=0.0008). The COVID subjects with hypertension were 42% vs.67% in the Control group (p=0,2), and diabetes was similar in both groups The hospital stay in the COVID group was 14.5±11.5 days and the hospitalization death rate was 32.5% The COVID-19 group has shown an increase in MMP-9 activity compared with the Control group (0.38±0.072 UA;95%CI=0.23-0.52,p<0.0001). The MMP-9 activity increasing was independent of gender (p=0.45), age (p=0.93), BMI (p=0.3) or hypertension (p=0.6) and dependent of the COVID-19 infection (p<0.0001). Therefore, our data are showing that the COVID-19 infection was responsible for MMP-9 improvement in plasma of severe COVID-19 infection (p<0.0001) while all different analyses consistently showed a signi ficant effect of COVID-19 infection (p<0.0001) Conclusions: There is a signi ficant increase in the MMP-9 plasmatic activity in severe COVID-19 patients independently of sex, age, obesity, and hypertension Therefore, MMP-9 may be a potential new target for acute lung injury therapy in patients with COVID-19.