Disaturated-phosphatidylcholine and Surfactant protein-B turnover in human acute lung injury and in control patients

<p>Abstract</p> <p>Background</p> <p>Patients with Adult Respiratory Distress Syndrome (ARDS) and Acute Lung Injury (ALI) have low concentrations of disaturated-phosphatidylcholine and surfactant protein-B in bronchoalveolar lavage fluid. No information is available on their turnover.</p> <p>Objectives</p> <p>To analyze disaturated-phosphatidylcholine and surfactant protein-B turnover in patients with ARDS/ALI and in human adults with normal lungs (controls).</p> <p>Methods</p> <p>²H₂O as precursor of disaturated-phosphatidylcholine-palmitate and 1¹³C-Leucine as precursor of surfactant protein-B were administered intravenously to 12 patients with ARDS/ALI and to 8 controls. Disaturated-phosphatidylcholine and surfactant protein-B were isolated from serial tracheal aspirates, and their fractional synthetic rate was derived from the ²H and ¹³C enrichment curves, obtained by gas chromatography mass spectrometry. Disaturated-phosphatidylcholine, surfactant protein-B, and protein concentrations in tracheal aspirates were also measured.</p> <p>Results</p> <p>1) Surfactant protein-B turned over at faster rate than disaturated-phosphatidylcholine both in ARDS/ALI patients and in controls. 2) In patients with ARDS/ALI the fractional synthesis rate of disaturated-phosphatidylcholine was 3.1 times higher than in controls (p < 0.01), while the fractional synthesis rate of surfactant protein-B was not different. 3) In ARDS/ALI patients the concentrations of disaturated-phosphatidylcholine and surfactant protein-B in tracheal aspirates were markedly and significantly reduced (17% and 40% of the control values respectively).</p> <p>Conclusions</p> <p>1) Disaturated-phosphatidylcholine and surfactant protein-B have a different turnover both in healthy and diseased lungs. 2) In ARDS/ALI the synthesis of these two surfactant components may be differently regulated.</p

Low-level laser therapy decreases local effects induced by myotoxins isolated from Bothrops jararacussu snake venom

The prominent myotoxic effects induced by Bothrops jararacussu crude venom are due, in part, to its polycationic myotoxins, BthTX-I and BthTX-II. Both myotoxins have a phospholipase A2 structure: BthTX-II is an active enzyme Asp-49 PLA2, while BthTX-I is a Lys-49 PLA2 devoid of enzymatic activity. In this study, the effect of low-level laser therapy (LLLT), 685 nm laser at a dose of 4.2 J/cm2 on edema formation, leukocyte influx and myonecrosis caused by BthTX-I and BthTX-II, isolated from Bothrops jararacussu snake venom, was analyzed. BthTX-I and BthTX-II caused a significant edema formation, a prominent leukocyte infiltrate composed predominantly by neutrophils and myonecrosis in envenomed gastrocnemius muscle. LLLT significantly reduced the edema formation, neutrophil accumulation and myonecrosis induced by both myotoxins 24 hours after the injection. LLLT reduced the myonecrosis caused by BthTX-I and BthTX-II, respectively, by 60 and 43%; the edema formation, by 41 and 60.7%; and the leukocyte influx, by 57.5 and 51.6%. In conclusion, LLLT significantly reduced the effect of these snake toxins on the inflammatory response and myonecrosis. These results suggest that LLLT should be considered a potential therapeutic approach for treatment of local effects of Bothrops species venom.Fundação Vale Paraibana de Ensin

Characterization of oil shale residue and rejects from irati formation by electron paramagnetic resonance

In this study, sedimentary organic matter of oil shale rejects, calschist, shale fine and the so called retorted shale from Irati formation was characterized. EPR was used to analyse the samples regarding loss of signal in g = 2.003 associated to the organic free radical with the calcined samples and washing with hydrogen peroxide. The radical signal was detected in all samples, however, for the calschist and shale fine samples another signal was identified at g = 2.000 which disappeared when the sample was heated at 400 ºC. Hydrogen peroxide washing was also performed and it was noted that after washing the signal appeared around g = 2.000 for all samples, including retorted shale, which might be due to the quartz E1 defect

Cardiovascular Risk Factors and Risk of Alzheimer Disease and Mortality: A Latent Class Approach

BackgroundCardiovascular risk factors co‐occur with one another, and little is known about the extent of their clustering and risk of Alzheimer disease (AD). We identify groups of cardiovascular risk factors in cognitively normal individuals and investigate between‐group differences in incident AD and death.Methods and ResultsCognitively normal individuals were recruited from the National Alzheimer's Coordinator Center. A latent class analysis was conducted with hypertension, hypercholesterolemia, heart condition, stroke, smoking history, diabetes, and high body mass index. Between‐group differences in the incidence of AD, mortality, and mortality‐adjusted AD were investigated. This study included 12 412 cognitively normal individuals (average follow‐up, 65 months). Three groups were identified: (1) low probabilities of cardiovascular risk factors (reference; N=5398 [43%]), (2) hypertension and hypercholesterolemia (vascular‐dominant; N=5721 [46%]), and (3) hypertension, hypercholesterolemia, diabetes, and high body mass index (vascular‐metabolic; N=1293 [10%]). Both vascular groups were significantly older, had more men, were slightly less educated, and were slightly more cognitively impaired than the reference group (all P<0.05). However, only the vascular‐metabolic group had a significantly younger age of death compared with the reference group (84.3 versus 88.7 years, P<0.001). Only the vascular‐dominant group had a greater incidence of AD (odds ratio [OR], 1.30; P<0.001) compared with the reference group. Mortality was greater in the vascular‐dominant (OR, 3.26; P<0.001) and vascular‐metabolic groups (OR, 1.84; P=0.02). Mortality‐adjusted AD was greater in the vascular‐dominant (OR, 1.54; P=0.02) and vascular‐metabolic groups (OR, 1.46; P=0.04).ConclusionsThree distinct cardiovascular risk factor groups were identified in cognitively normal elderly individuals. Only the vascular‐dominant group was associated with a greater incidence of AD. Selective mortality may contribute to the attenuated association between the vascular‐metabolic group and incident AD.publishedVersio

Detecting neurodevelopmental trajectories in congenital heart diseases with a machine-learning approach

We aimed to delineate the neuropsychological and psychopathological profiles of children with congenital heart disease (CHD) and look for associations with clinical parameters. We conducted a prospective observational study in children with CHD who underwent cardiac surgery within five years of age. At least 18\ua0months after cardiac surgery, we performed an extensive neuropsychological (intelligence, language, attention, executive function, memory, social skills) and psychopathological assessment, implementing a machine-learning approach for clustering and influencing variable classification. We examined 74 children (37 with CHD and 37 age-matched controls). Group comparisons have shown differences in many domains: intelligence, language, executive skills, and memory. From CHD questionnaires, we identified two clinical subtypes of psychopathological profiles: a small subgroup with high symptoms of psychopathology and a wider subgroup of patients with ADHD-like profiles. No associations with the considered clinical parameters were found. CHD patients are prone to high interindividual variability in neuropsychological and psychological outcomes, depending on many factors that are difficult to control and study. Unfortunately, these dysfunctions are under-recognized by clinicians. Given that brain maturation continues through childhood, providing a significant window for recovery, there is a need for a lifespan approach to optimize the outcome trajectory for patients with CHD

Effect of preoperative pulmonary hemodynamic and cardiopulmonary bypass on lung function in children with congenital heart disease

In children with congenital heart disease (CHD), pulmonary blood flow (Qp) contributes to alterations of pulmonary mechanics and gas exchange, while cardiopulmonary bypass (CPB) induces lung edema. We aimed to determine the effect of hemodynamics on lung function and lung epithelial lining fluid (ELF) biomarkers in biventricular CHD children undergoing CPB. CHD children were classified as high Qp (n = 43) and low Qp (n = 17), according to preoperative cardiac morphology and arterial oxygen saturation. We measured ELF surfactant protein B (SP-B) and myeloperoxidase activity (MPO) as indexes of lung inflammation and ELF albumin as index of alveolar capillary leak in tracheal aspirate (TA) samples collected before surgery and in 6 hourly intervals within 24 h after surgery. At the same time points, we recorded dynamic compliance and oxygenation index (OI). The same biomarkers were measured in TA samples collected from 16 infants with no cardiorespiratory diseases at the time of endotracheal intubation for elective surgery. Preoperative ELF biomarkers in CHD children were significantly increased than those found in controls. In the high Qp, ELF MPO and SP-B peaked 6 h after surgery and tended to decrease afterward, while they tended to increase within the first 24 h in the low Qp. ELF albumin peaked 6 h after surgery and decreased afterwards in both CHD groups. Dynamic compliance/kg and OI significantly improved after surgery only in the High Qp. Conclusion: In CHD children, lung mechanics, OI, and ELF biomarkers were significantly affected by CPB, according to the preoperative pulmonary hemodynamics.What is Known:• Congenital heart disease children, before cardiopulmonary run, exhibit changes in respiratory mechanics, gas exchange, and lung inflammatory biomarkers that are related to the preoperative pulmonary hemodynamics.• Cardiopulmonary bypass induces alteration of lung function and epithelial lining fluid biomarkers according to preoperative hemodynamics.What is New:• Our findings can help to identify children with congenital heart disease at high risk of postoperative lung injury who may benefit of tailored intensive care strategies, such as non-invasive ventilation techniques, fluid management, and anti-inflammatory drugs that can improve cardiopulmonary interaction in the perioperative period

Protective continuous ventilation strategy during cardiopulmonary bypass in children undergoing surgery for congenital heart disease: a prospective study

OBJECTIVES: The aim of this study was to evaluate if a 'protective' (low-tidal/low-frequency) ventilation strategy can shorten the postoperative ventilation time and minimize acute lung injury in children with congenital heart disease (CHD) undergoing repair with cardiopulmonary bypass (CPB). METHODS: This is a single-centre prospective, interventional study, including children with CHD under the age of 5 years, undergoing open-heart surgery with a CPB &gt;60 min, in hypothermia, haemodynamically stable, and without evident genetic abnormalities. Assist-control ventilation (tidal volume of 4 ml/kg, 10 breaths/min, positive end-expiratory pressure 5 cmH2O and FiO2 0.21) was applied in a cohort of patients during CPB. We compared clinical outcomes and in fully ventilated versus non-ventilated (control) patients. Propensity score was used to weigh ventilated and control groups to correct for the effect of other confounding clinical variables. Clinical and ventilation parameters and lung inflammatory biomarkers in tracheal aspirates were measured. The primary outcome was the postoperative intubation time of more or less than 48 h. RESULTS: We included 140 children (53 ventilated, 87 non-ventilated) with different CHD. There were no deaths or adverse events in ventilated patients. Using a weighted generalized linear model, we found no sufficient evidence for an effect of intraoperative ventilation on postoperative intubation time [estimate 0.13 (95% confidence interval, -0.08; 0.35), P = 0.22]. CONCLUSIONS: Continuous low-tidal/low-frequency mechanical ventilation during CPB is safe and harmless. However, no significant advantages were found when compared to non-ventilated patients in terms of postoperative ventilation time

Exercise intolerance at high altitude (5050 m): critical power and W'

The relationship between work rate (WR) and its tolerable duration (t(LIM)) has not been investigated at high altitude (HA). At HA (5050 m) and at sea level (SL), six subjects therefore performed symptom-limited cycle-ergometry: an incremental test (IET) and three constant-WR tests (% of IET WR(max), HA and SL respectively: WR(1) 70±8%, 74±7%; WR(2) 86±14%, 88±10%; WR(3) 105±13%, 104±9%). The power asymptote (CP) and curvature constant (W') of the hyperbolic WR-t(LIM) relationship were reduced at HA compared to SL (CP: 81±21 vs. 123±38 W; W': 7.2±2.9 vs. 13.1±4.3 kJ). HA breathing reserve (estimated maximum voluntary ventilation minus end-exercise ventilation) was also compromised (WR(1): 25±25 vs. 50±18 l min(-1); WR(2): 4±23 vs. 38±23 l min(-1); WR(3): -3±18 vs. 32±24 l min(-1)) with near-maximal dyspnea levels (Borg) (WR(1): 7.2±1.2 vs. 4.8±1.3; WR(2): 8.8±0.8 vs. 5.3±1.2; WR(3): 9.3±1.0 vs. 5.3±1.5). The CP reduction is consistent with a reduced O(2) availability; that of W' with reduced muscle-venous O(2) storage, exacerbated by ventilatory limitation and dyspnea. Copyright © 2011 Elsevier B.V. All rights reserved

Adolescent depression beyond DSM definition: a network analysis

Calls for refning the understanding of depression beyond diagnostic criteria have been growing in recent years. We examined the prevalence and relevance of DSM and non-DSM depressive symptoms in two Brazilian school-based adolescent samples with two commonly used scales, the Patient Health Questionnaire (PHQ-A) and the Mood and Feelings Questionnaire (MFQ). We analyzed cross-sectional data from two similarly recruited samples of adolescents aged 14–16 years, as part of the Identifying Depression Early in Adolescence (IDEA) study in Brazil. We assessed dimensional depressive symptomatology using the PHQ-A in the frst sample (n=7720) and the MFQ in the second sample (n=1070). We conducted network analyses to study symptom structure and centrality estimates of the two scales. Additionally, we compared centrality of items included (e.g., low mood, anhedonia) and not included in the DSM (e.g., low self-esteem, loneliness) in the MFQ. Sad mood and worthlessness items were the most central items in the network structure of the PHQ-A. In the MFQ sample, self-hatred and loneliness, two non-DSM features, were the most central items and DSM and non-DSM items in this scale formed a highly interconnected network of symptoms. Furthermore, analysis of the MFQ sample revealed DSM items not to be more frequent, severe or interconnected than non-DSM items, but rather part of a larger network of symptoms. A focus on symptoms might advance research on adolescent depression by enhancing our understanding of the disorder.publishedVersio