Ferricytochrome c Directly Oxidizes Aminoacetone to Methylglyoxal, a Catabolite Accumulated in Carbonyl Stress

Age-related diseases are associated with increased production of reactive oxygen and carbonyl species such as methylglyoxal. Aminoacetone, a putative threonine catabolite, is reportedly known to undergo metal-catalyzed oxidation to methylglyoxal, NH4+ ion, and H2O2 coupled with (i) permeabilization of rat liver mitochondria, and (ii) apoptosis of insulin-producing cells. Oxidation of aminoacetone to methylglyoxal is now shown to be accelerated by ferricytochrome c, a reaction initiated by one-electron reduction of ferricytochrome c by aminoacetone without amino acid modifications. the participation of O-2(center dot-) and HO center dot radical intermediates is demonstrated by the inhibitory effect of added superoxide dismutase and Electron Paramagnetic Resonance spin-trapping experiments with 5,5'-dimethyl-1-pyrroline-N-oxide. We hypothesize that two consecutive one-electron transfers from aminoacetone (E-0 values = -0.51 and -1.0 V) to ferricytochrome c (E-0 = 0.26 V) may lead to aminoacetone enoyl radical and, subsequently, imine aminoacetone, whose hydrolysis yields methylglyoxal and NH4+ ion. in the presence of oxygen, aminoacetone enoyl and O-2(center dot-) radicals propagate aminoacetone oxidation to methylglyoxal and H2O2. These data endorse the hypothesis that aminoacetone, putatively accumulated in diabetes, may directly reduce ferricyt c yielding methylglyoxal and free radicals, thereby triggering redox imbalance and adverse mitochondrial responses.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)INCT Processos Redox em Biomedicina (Brazil)Univ São Paulo, Dept Bioquim, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Bioquim & Biol Mol, São Paulo, BrazilUniversidade Federal de São Paulo, Inst Ciencias Ambientais Quim & Farmaceut, São Paulo, BrazilUniv São Paulo, Dept Fis & Informat, São Paulo, BrazilUniv Fed ABC, Ctr Ciencias Nat & Humanas, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Bioquim & Biol Mol, São Paulo, BrazilUniversidade Federal de São Paulo, Inst Ciencias Ambientais Quim & Farmaceut, São Paulo, BrazilWeb of Scienc

Assessing bias in aerial surveys for cetaceans: Results from experiments conducted with the franciscana dolphin

Line transect aerial surveys are widely used for estimating abundance of biological populations, including threatened species. However, estimates obtained with data collected from aircraft are often underestimated because of visibility bias and bias in estimating group sizes from a fast-moving platform. An assessment of multiple sources of bias in aerial surveys were carried out in Brazilian coastal waters by experiments on multiple survey platforms (i.e., boat, airplane and helicopter). These studies focused on evaluating visibility bias (perception and availability bias) and potential differences in the estimation of group sizes from different types of platforms used in franciscana (Pontoporia blainvillei) abundance surveys. The ultimate goal was to develop correction factors to improve accuracy of estimates of density and population size for this threatened dolphin. Estimates of density and group sizes computed from boats were assumed to be unbiased and were compared to estimates of these quantities obtained from an airplane in the same area and period. In addition, helicopter surveys were conducted in two areas where water turbidity differed (clear vs. murky waters) to determine surfacing-diving intervals of franciscana groups and to estimate availability for aerial platforms. Abundance computed from the aerial survey data underestimated the true abundance by about 4-5 times, with ~70% of the total bias resulting from visibility bias (~80% from availability bias and ~20% from perception bias) and ~30% from bias in estimates of group size. The use of multiple survey platforms in contrasting habitats provided the opportunity to compute correction factors that can be used to refine range wide abundance estimates of the threatened franciscana given certain assumptions are met. Visibility bias and group size bias were substantial and clearly indicate the importance for accounting for such correction factors to produce unequivocal population assessment based on aerial survey data.Fil: Sucunza, Federico. Grupo de Estudio de Mamiferos Aquaticos de Rio Grande Do Sul.; Brasil. Universidade Federal de Juiz de Fora; Brasil. Instituto Aqualie; BrasilFil: Danilewicz, Daniel. Instituto Aqualie; Brasil. Grupo de Estudio de Mamiferos Aquaticos de Rio Grande Do Sul.; Brasil. Universidade Federal de Juiz de Fora; BrasilFil: Andriolo, Artur. Instituto Aqualie; Brasil. Universidade Federal de Juiz de Fora; BrasilFil: de Castro, Franciele R.. Instituto Aqualie; BrasilFil: Cremer, Marta. Universidade da Região de Joinville; BrasilFil: Denuncio, Pablo Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; ArgentinaFil: Ferreira, Emanuel. Associação R3 Animal; BrasilFil: Flores, Paulo A. C.. Instituto Chico Mendes para a Conservação da Biodiversidade; BrasilFil: Ott, Paulo H.. Universidade Estadual do Rio Grande do Sul; Brasil. Grupo de Estudio de Mamiferos Aquaticos de Rio Grande Do Sul.; BrasilFil: Perez, Martin S.. Grupo de Estudio de Mamiferos Aquaticos de Rio Grande Do Sul.; BrasilFil: Pretto, Dan. Instituto Chico Mendes Para A Conservação Da Biodiversidade; BrasilFil: Sartori, Camila M.. Universidade da Região de Joinville; BrasilFil: Secchi, Eduardo Resende. Universidade Federal do Rio Grande; BrasilFil: Zerbini, Alexandre. Marine Ecology And Telemetry Research; Estados Unidos. Cascadia Research Collective; Estados Unidos. Instituto Aqualie; Brasil. Universidade Federal de Juiz de Fora; Brasil. The George Washington University; Estados Unido

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Glycated human serum albumin isolated from poorly controlled diabetic patients impairs cholesterol efflux from macrophages: An investigation by mass spectrometry

none10noneCastilho, Gabriela; Sartori, Camila H.; Machado-Lima, Adriana; Nakandakare, Edna R.; Corrêa-Giannella, Maria Lucia C.; Roverso, Marco; Porcu, Simona; Lapolla, Annunziata; Traldi, Pietro; Passarelli, MarisaCastilho, Gabriela; Sartori, Camila H.; Machado Lima, Adriana; Nakandakare, Edna R.; Corrêa Giannella, Maria Lucia C.; Roverso, Marco; Porcu, Simona; Lapolla, Annunziata; Traldi, Pietro; Passarelli, Maris

Low-temperature EPR spectra of ferricyt <i>c</i> treated with AA.

<p>(A) EPR spectra of (300 µM) ferricyt <i>c</i> after a 12-h incubation with (1.0–5.0 mM) AA. (B) Time-response ERP spectra of ferricyt <i>c</i> treated with (1.0 mM) AA for 30 min. Incubation conditions: 50 mM phosphate buffer, pH 7.4, at 37°C. (C) MCD spectra of ferricyt <i>c</i> in the presence of AA. The conditions are ferricyt <i>c</i> (40 µM) MCD spectrum before treatment with AA (thick line) and MCD ferricyt <i>c</i> spectrum after 12 h of (5.0 mM) AA treatment (thin line). (D) CD spectrum of ferricyt <i>c</i> treated with 5.0 mM AA. Incubation conditions: 50 mM phosphate buffer, pH 7.4, at 37°C.</p

EPR spin-trapping studies and computer simulation of the AA system in the presence and absence of ferricyt <i>c</i>, under aerobic conditions.

<p>EPR spectra of DMPO-radical adducts were obtained after a 4-min incubation of (15 mM) AA at 25°C with (150 µM) cyt <i>c</i> in 50 mM phosphate buffer (pH 7.4) with (400 mM) DMPO. (A) Experimental spectrum (trace a) and computer simulations (traces b-d) of the DMPO/AA system, (B) Experimental spectrum (trace a) and computer simulations of the DMPO/AA/cyt <i>c</i> system (traces b-e). Trace <i>c</i> in panels A and B represents the DMPO-<b>^•</b>OH adduct spectrum, and trace d can attributable to the DMPO-AA<b>^•</b> adduct. Trace e in panel B represents an unknown DMPO adduct. Instrumental conditions: microwave power, 20.2 mW; modulation amplitude, 1.0; time constant, 1.63 s; scan rate 0.1 G/s; and receiver gain, 1.12×106.</p

Proposed mechanism of AA oxidation catalyzed by iron and copper ions (Adapted from Dutra et al.[14]).

<p>Proposed mechanism of AA oxidation catalyzed by iron and copper ions (Adapted from Dutra et al.<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0057790#pone.0057790-Dutra1" target="_blank">[14]</a>).</p

EPR spin-trapping studies of the ferricyt <i>c</i>/AA system under aerobic conditions.

<p>EPR spectra of DMPO-radical adducts were obtained after a 4-min incubation of 15 mM AA at 25°C in 50 mM phosphate buffer (pH 7.4) with (25 mM) DMPO: (A) DMPO experiments, (B) DMPO in the presence of DMSO 30% v/v, (C) DMPO in the presence of ethanol 30% v/v. For all of the figures: (a) control with ferricyt <i>c</i> (150 µM); (b) AA (15mM); (c) AA (15 mM)+desferoxamine (100 µM); (d) ferricyt <i>c</i> (150 µM)+AA (15 mM); (e) system d+CuZnSOD (50 U/mL); (f) system d+catalase (15 µM) for Fig. 2A and 2C only. Instrumental conditions: microwave power, 20.2 mW; modulation amplitude, 1.0; time constant, 1.63 s; scan rate 0.1 G/s; and receiver gain, 1.12×106.</p

Oxygen uptake by AA in the presence of ferricyt <i>c</i>.

<p>Experimental conditions: (50 µM) ferricyt <i>c</i> in the presence or absence of (5.0 mM) AA in 50 mM phosphate buffer, pH 7.4, at 37°C for 30 min. Experiments were performed in the absence or presence of catalase (5.0 µM) or CuZnSOD (50 U/mL). Data are representative of five independent runs. *p<0.05 relative to the system containing only AA and #p<0.05 relative to the AA/ferricyt <i>c</i> system.</p