Dexamethasone Treatment Reverses Cognitive Impairment but Increases Brain Oxidative Stress in Rats Submitted to Pneumococcal Meningitis

Pneumococcal meningitis is associated with a significant mortality rate and neurologic sequelae. The animals received either 10 μL of saline or a S. pneumoniae suspension and were randomized into different groups: sham: placebo with dexamethasone 0.7 mg/kg/1 day; placebo with dexamethasone 0.2 mg/kg/7 days; meningitis groups: dexamethasone 0.7 mg/kg/1 day and dexamethasone 0.2 mg/kg/7 days. Ten days after induction we evaluated memory and oxidative stress parameters in hippocampus and cortex. In the step-down inhibitory avoidance task, we observed memory impairment in the meningitis group with dexamethasone 0.2 mg/kg/7 days. The lipid peroxidation was increased in hippocampus in the meningitis groups with dexamethasone and in cortex only in the meningitis group with dexamethasone 0.2 mg/kg/7 days. The protein carbonyl was increased in hippocampus in the meningitis groups with dexamethasone and in cortex in the meningitis groups with and without dexamethasone. There was a decrease in the proteins integrity in hippocampus in all groups receiving treatment with dexamethasone and in cortex in all groups with dexamethasone (0.7 mg/kg/1 day). The mitochondrial superoxide was increased in the hippocampus and cortex in the meningitis group with dexamethasone 0.2 mg/kg/7 days. Our findings demonstrate that dexamethasone reverted cognitive impairment but increased brain oxidative stress in hippocampus and cortex in Wistar rats ten days after pneumococcal meningitis induction

Hemoparasites effect on interferon-gamma and miRNA 125b expression in Bubalus bubalis

This study aimed to determine and evaluate the effect of the g4467 G>A SNP on the expression profile of IFN-γ and miRNA 125b in dairy buffaloes (Bubalus bubalis) with and without hemoparasites. Molecular diagnosis was performed by Polymerase Chain Reaction (PCR) on 145 buffaloes for Babesia spp., Trypanosoma vivax, and Anaplasma marginale. All buffaloes were investigated for the presence or absence of the polymorphism and genotyped using the restriction enzyme. Real-time PCR (RT-qPCR) quantified the expression of IFN-γ and miRNA 125b. All buffaloes were negative for Babesia spp. and A. marginale, and only 12 were positive for T. vivax. The genotypes GG, GA, and AA were found in proportions of 3.4%, 2.1%, and 94.5%, respectively. The A allele was the most frequent (95.5%). The SNP showed deviation from Hardy-Weinberg equilibrium (HWE) (P<0.05) and a deficit of heterozygotes with FIS 0.759. All animals of the found genotypes expressed both genes, except for GG positive for T. vivax. IFN-γ expression was higher for GA and GG negative (P<0.05) and AA positive. However, miRNA 125b expression was lower for AA and GA positive and higher for AA, GA, and GG negative. AA-positive buffaloes for T. vivax may exhibit susceptibility due to higher IFN-γ expression and lower miRNA 125b. GG and GA-negative buffaloes exhibited higher expression in both, suggesting they have greater resistance to positive ones

Multiple effects of toxins isolated from Crotalus durissus terrificus on the hepatitis C virus life cycle

Hepatitis C virus (HCV) is one of the main causes of liver disease and transplantation worldwide. Current therapy is expensive, presents additional side effects and viral resistance has been described. Therefore, studies for developing more efficient antivirals against HCV are needed. Compounds isolated from animal venoms have shown antiviral activity against some viruses such as Dengue virus, Yellow fever virus and Measles virus. In this study, we evaluated the effect of the complex crotoxin (CX) and its subunits crotapotin (CP) and phospholipase A2 (PLA2-CB) isolated from the venom of Crotalus durissus terrificus on HCV life cycle. Huh 7.5 cells were infected with HCVcc JFH-1 strain in the presence or absence of these toxins and virus was titrated by focus formation units assay or by qPCR. Toxins were added to the cells at different time points depending on the stage of virus life cycle to be evaluated. The results showed that treatment with PLA2-CB inhibited HCV entry and replication but no effect on HCV release was observed. CX reduced virus entry and release but not replication. By treating cells with CP, an antiviral effect was observed on HCV release, the only stage inhibited by this compound. Our data demonstrated the multiple antiviral effects of toxins from animal venoms on HCV life cycle

Dinâmica e estoque de carbono em floresta primária na região de Manaus/AM

Este trabalho analisou dados de três inventários florestais realizados na área da Floresta Experimental, pertencente à Embrapa Amazônia Ocidental e localizada no km 54 da BR-174, em Manaus/AM. O objetivo foi estudar a dinâmica da floresta - taxas de incremento, recrutamento e mortalidade - além do estoque de carbono, em uma área de floresta primária, sem qualquer tipo de intervenção. Os inventários foram realizados nos anos de 2005, 2007 e 2010, em 15 parcelas permanentes de 1 hectare cada, onde foram mensuradas todas as árvores com diâmetro a 1,3 m de altura do solo (DAP) superior a 10 cm. Foram calculadas as taxas de recrutamento e mortalidade, os incrementos periódicos anuais (IPAs) em termos de DAP, área basal e volume, as biomassas fresca e seca acima do nível do solo e total e o estoque de carbono da vegetação. As taxas de recrutamento foram de 2% e 1,8% e as de mortalidade foram de 0,95% e 1,3% para os períodos entre 2005 e 2007 e 2007 e 2010, respectivamente. O volume foi de 345,62 m3 ha-1 para o ano de 2005, aumentando para 360,67 m3 ha-1 em 2010, com IPAs de 4,32 m3 ha-1 ano-1 entre 2005 e 2007 e 1,31 m3 ha-1 ano-1 entre 2007 e 2010. O estoque de carbono total teve um acréscimo de 173,63 t C ha-1 em 2005 para 181,01 t C ha-1 em 2010, confirmando que a floresta acumulou carbono no período, atuando assim como sumidouro.This study analyzed data from three forest inventories conducted in the Experimental Forest, which belongs to Embrapa Western Amazon basin and is located at km 54 on BR-174, Manaus / AM. The aim was to study forest dynamics - the rates of recruitment, growth and mortality - in addition to carbon storage in an area of primary forest, without any intervention. The surveys were conducted in the years 2005, 2007 and 2010 in 15 permanent plots of 1 hectare each. There, all trees with diameter at breast height (DBH) above 10 cm were measured. We calculated the rates of recruitment and mortality, the periodic annual increments (PAIs) in terms of DBH, basal area and volume, fresh and dry biomass above the soil and total carbon storage in the vegetation. The recruitment rates were 2.0 percent and 1.8 percent, and mortality were 0.95 percent and 1.3 percent for the periods between 2005 and 2007 and 2007 and 2010, respectively. The volume was 345.62 m3 ha-1 for the year 2005, rising to 360.67 m3 ha-1 in 2010 with PAIs of 4.32 m3 ha-1 yr-1 between 2005 and 2007 and 1.31 m3 ha-1 yr-1 between 2007 and 2010. The total carbon storage increased from 173.63 t C ha-1 in 2005 to 181.01 t C ha-1 in 2010, confirming that the forest accumulated carbon in the period, acting as a sink

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure &lt;= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt