RESUMO
High altitude-related excessive erythrocytosis (EE) is associated with increased cardiovascular risk. The experimental aim of this study was to determine the effects of microvesicles isolated from Andean highlanders with EE on endothelial cell inflammation, oxidative stress, apoptosis, and nitric oxide (NO) production. Twenty-six male residents of Cerro de Pasco, Peru (4,340 m), were studied: 12 highlanders without EE (age: 40 ± 4 yr; BMI: 26.4 ± 1.7; Hb: 17.4 ± 0.5 g/dL, Spo2: 86.9 ± 1.0%) and 14 highlanders with EE (43 ± 4 yr; 26.2 ± 0.9; 24.4 ± 0.4 g/dL; 79.7 ± 1.6%). Microvesicles were isolated, enumerated, and collected from plasma by flow cytometry. Human umbilical vein endothelial cells were cultured and treated with microvesicles from highlanders without and with EE. Microvesicles from highlanders with EE induced significantly higher release of interleukin (IL)-6 (89.8 ± 2.7 vs. 77.1 ± 1.9 pg/mL) and IL-8 (62.0 ± 2.7 vs. 53.3 ± 2.2 pg/mL) compared with microvesicles from healthy highlanders. Although intracellular expression of total NF-κB p65 (65.3 ± 6.0 vs. 74.9 ± 7.8.9 AU) was not significantly affected in cells treated with microvesicles from highlanders without versus with EE, microvesicles from highlanders with EE resulted in an â¼25% higher (P < 0.05) expression of p-NF-κB p65 (173.6 ± 14.3 vs. 132.8 ± 12.2 AU). Cell reactive oxygen species production was significantly higher (76.4.7 ± 5.4 vs. 56.7 ± 1.7% of control) and endothelial nitric oxide synthase (p-eNOS) activation (231.3 ± 15.5 vs. 286.6 ± 23.0 AU) and NO production (8.3 ± 0.6 vs. 10.7 ± 0.7 µM/L) were significantly lower in cells treated with microvesicles from highlanders with versus without EE. Cell apoptotic susceptibility was not significantly affected by EE-related microvesicles. Circulating microvesicles from Andean highlanders with EE increased endothelial cell inflammation and oxidative stress and reduced NO production.NEW & NOTEWORTHY In this study, we determined the effects of microvesicles isolated from Andean highlanders with excessive erythrocytosis (EE) on endothelial cell inflammation, oxidative stress, apoptosis, and NO production. Microvesicles from highlanders with EE induced a dysfunctional response from endothelial cells characterized by increased cytokine release and expression of active nuclear factor-κB and reduced nitric oxide production. Andean highlanders with EE exhibit dysfunctional circulating extracellular microvesicles that induce a proinflammatory, proatherogenic endothelial phenotype.
Assuntos
Aclimatação , Altitude , Micropartículas Derivadas de Células/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Policitemia/sangue , Adulto , Apoptose , Estudos de Casos e Controles , Micropartículas Derivadas de Células/patologia , Células Cultivadas , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Mediadores da Inflamação/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Masculino , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Estresse Oxidativo , Peru , Fenótipo , Policitemia/patologia , Policitemia/fisiopatologia , Espécies Reativas de Oxigênio/metabolismo , Fator de Transcrição RelA/metabolismoRESUMO
NEW FINDINGS: What is the central question of this study? Are coagulation and fibrinolytic factors disrupted in Andean highlanders with excessive erythrocytosis? What is the main finding and its importance? Excessive erythrocytosis is not associated with prothombotic disruptions in coagulation or the fibrinolytic system in Andean highlanders. Impairments in coagulation and fibrinolysis may not contribute to the increased vascular risk associated with excessive erythrocytosis. ABSTRACT: Increased coagulation and reduced fibrinolysis are central factors underlying thrombotic risk and events. High altitude-induced excessive erythrocytosis (EE) is prevalent in Andean highlanders, contributing to increased cardiovascular risk. Disruption in the coagulation-fibrinolytic axis resulting in uncontrolled fibrin deposition might underlie the increased thrombotic risk associated with high-altitude EE. The experimental aim of this study was to determine whether EE is associated with a prothrombotic blood coagulation and fibrinolytic profile in Andean highlanders. Plasma coagulation factors (von Willebrand factor and factors VII, VIII and X), fibrinolytic factors [tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1)] and D-dimer levels were determined in 26 male residents of Cerro de Pasco, Peru (4340 m a.s.l.): 12 without EE (age, 40 ± 13 years; haemoglobin, 17.4 ± 1.9 g/dl) and 14 with EE (age, 43 ± 15 years; haemoglobin, 24.4 ± 1.6 g/dl). There were no significant differences in von Willebrand factor (40.5 ± 24.8 vs. 45.5 ± 22.4%), factor VII (77.0 ± 14.5 vs. 72.5 ± 8.9%), factor VIII (55.6 ± 19.8 vs. 60.7 ± 26.8%) and factor X (73.9 ± 8.3 vs. 67.3 ± 10.9%) between the Andean highlanders without or with EE. The t-PA antigen (8.5 ± 3.6 vs. 9.6 ± 5.4 ng/ml), t-PA activity (5.5 ± 2.4 vs. 5.8 ± 1.6 IU/ml), PAI antigen (45.0 ± 33.8 vs. 40.5 ± 15.8 ng/ml), PAI-1 activity (0.24 ± 0.09 vs. 0.25 ± 0.11 IU/ml) and the molar concentration ratio of active t-PA to active PAI-1 (1:0.051 ± 0.034 vs. 1:0.046 ± 0.021 mmol/l) were also similar between the groups, as were D-dimer levels (235.0 ± 126.4 vs. 268.4 ± 173.7 ng/ml). Collectively, the results of the present study indicate that EE is not associated with a hypercoagulable, hypofibrinolytic state in Andean highlanders.
Assuntos
Coagulação Sanguínea , Fibrinólise , Policitemia , Adulto , Altitude , Coração , Hemoglobinas , Humanos , Masculino , Pessoa de Meia-Idade , América do SulRESUMO
BACKGROUND & AIMS: Cardiovascular disease (CVD) is highly prevalent in Suriname, a middle-income country with predominantly people of African and Asian ancestry. We examined whether the more comprehensive body composition measures determined by bioelectrical impedance analysis (BIA) are superior to the more traditional BMI and waist measures in relation to cardiovascular risk. METHODS: Data from the cross-sectional Healthy Life in Suriname (HELISUR) study were used to calculate BMI, waist-hip ratio, waist-to-height ratio, and waist circumference. BIA was used to estimate fat percentage, fat-free mass index, and fat-to-fat-free mass ratio. High cardiovascular risk was defined as 1) a 10-year Framingham coronary heart disease risk score ≥10% in African-Surinamese and ≥12% in Asian-Surinamese, and 2) an increased arterial stiffness (pulse wave velocity >10 m/s). Using logistic regression analysis, we pre-selected the strongest correlate (i.e. lowest p-value below 0.05) of all body composition items for both outcomes of cardiovascular risk separately, and subsequently, used forward logistic regression modelling to determine whether other measures added value to the initial model with the strongest correlate (-2 log-likelihood (-2LL) of initial model minus -2LL of new model, χ-square statistic >3.841, 1 df). Analyses were adjusted for sex, age and ethnicity. RESULTS: We examined 691 participants (65% women; 48% African-Surinamese) with a mean age of 42 (SD 14) years. Waist circumference was the strongest correlate for high 10-year CVD risk in the total group, in men and African-Surinamese. In Asian-Surinamese, fat-free mass index was the strongest correlate of high 10-year CVD risk. Increased arterial stiffness was most strongly related with waist-to-height ratio in the total group and in African-Surinamese, and with BMI in men. None of the measures were significantly associated in women (for both outcomes) and Asian-Surinamese (for increased arterial stiffness). Forward selection showed that only BMI added value next to waist-to-height ratio in the total group in relation to increased arterial stiffness. CONCLUSIONS: Waist measures, in particular waist circumference and waist-to-height ratio, and BMI should be used in African and Asian-Surinamese to identify who is at increased cardiovascular risk. Overall, we found little advantage in using BIA measures rather than simple anthropometric measures.
Assuntos
Povo Asiático/etnologia , População Negra/etnologia , Composição Corporal/fisiologia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Adulto , Índice de Massa Corporal , Estudos Transversais , Impedância Elétrica , Feminino , Humanos , Masculino , Prevalência , Fatores de Risco , Suriname/epidemiologia , Circunferência da CinturaRESUMO
Discerning behaviours of free-ranging animals allows for quantification of their activity budget, providing important insight into ecology. Over recent years, accelerometers have been used to unveil the cryptic lives of animals. The increased ability of accelerometers to store large quantities of high resolution data has prompted a need for automated behavioural classification. We assessed the performance of several machine learning (ML) classifiers to discern five behaviours performed by accelerometer-equipped juvenile lemon sharks (Negaprion brevirostris) at Bimini, Bahamas (25°44'N, 79°16'W). The sharks were observed to exhibit chafing, burst swimming, headshaking, resting and swimming in a semi-captive environment and these observations were used to ground-truth data for ML training and testing. ML methods included logistic regression, an artificial neural network, two random forest models, a gradient boosting model and a voting ensemble (VE) model, which combined the predictions of all other (base) models to improve classifier performance. The macro-averaged F-measure, an indicator of classifier performance, showed that the VE model improved overall classification (F-measure 0.88) above the strongest base learner model, gradient boosting (0.86). To test whether the VE model provided biologically meaningful results when applied to accelerometer data obtained from wild sharks, we investigated headshaking behaviour, as a proxy for prey capture, in relation to the variables: time of day, tidal phase and season. All variables were significant in predicting prey capture, with predations most likely to occur during early evening and less frequently during the dry season and high tides. These findings support previous hypotheses from sporadic visual observations.
RESUMO
Three-dimensional treatment planning for the intact breast was performed on two patients who had undergone CT scanning. A total of 38 treatment plans were evaluated. Multiple plans were evaluated for each patient including plans with and without inhomogeneity corrections, plans using varying photon energies of 60Co, 4 MV, 6 MV, 10 MV, and 15 MV, and three-dimensionally unconstrained plans. Increased hot spots were appreciated in the central axis plane when lung inhomogeneity corrections were used. Additional hot spots were appreciated in off-axis planes towards the cephalad and caudad aspects of the target volume because of lung inhomogeneity corrections and changes in the breast contour. The use of 60Co was associated with an increase in the magnitude and volume of hot spots, whereas the use of higher energy photons such as 10 MV and 15 MV was associated with an unacceptable target coverage at shallow depths. Therefore, for the two patients studied, the use of a medium energy photon beam (such as from a 6 MV linear accelerator) appeared to be the energy of choice for treatment of the intact breast. The three-dimensionally unconstrained plans were able to improve slightly upon the standard plans, particularly with relationship of dose to normal tissue structures. Areas for future research were identified, including the use of tissue compensators.