Hemodynamic and metabolic effects of a new pediatric dobutamine formulation in hypoxic newborn pigs

Background: The aim of our study was to measure drug-related changes in hemodynamics and oxygen metabolism in response to different doses of an age-appropriate dobutamine formulation in hypoxic pigs. A secondary aim was to validate superior vena cava flow (SVCF) as a marker of cardiac index (CI) for subsequent clinical trials of this formulation in humans. Methods: Newborn pigs (n=18) were exposed to 2h-hypoxia (10-15% oxygen) followed by reoxygenation (21-30% oxygen 4h). After 1h-reoxygenation, pigs were randomized to: control group (no treatment), dobutamine infusion at a rate of 10-15μg/kg/min or 15-20μg/kg/min. Dobutamine groups received two dobutamine doses during 30min with a 60min washout period between doses. Cardiovascular profile and oxygen metabolism were monitored. In four animals an ultrasonic perivascular flow probe was placed around superior vena cava to measure SVCF. Results: Hypoxia significantly decreased CI, systemic-vascular-resistance and mean-arterial-bloodpressure (MABP). Dobutamine doses significantly increased heart-rate, CI and oxygen-delivery without changes in stroke-volume and MABP. Only 10-15μg/kg/min increased oxygen consumption and peripheral tissue oxygenation measured by Near-infrared-spectroscopy. A positive correlation was observed between SVCF and CI. Conclusion: The new pediatric dobutamine formulation improved hemodynamic status, with dose-specific differences in metabolic response. SVCF may be a useful surrogate for CI in subsequent clinical trials

Efecto de la edad y el nivel de vitamina E en dietas de pollos broiler sobre la modulación de la respuesta inmune.

La vitamina E pertenece al grupo de nutrientes con capacidad reguladora del sistema inmune (Koutsos y Klasing, 2008). En aves, la vitamina E induce cambios tanto en el sistema inmune innato como en el específico, mejora la función fagocítica de los macrófagos, amortigua la respuesta en fase aguda, disminuye la proporción de heterófilos y potencia la síntesis de anticuerpos (Koutsos y Klasing, 2008; Khan et al., 2012). Recientemente se ha demostrado que parte del efecto de la vitamina E está ligado a su capacidad de actuar directamente sobre factores de transcripción nuclear que modulan la expresión de citoquinas, tales como el factor-Kappa B o el PPAR γ (Koutsos y Klasing, 2008; Nakamura y Omaye, 2009). Por otro lado, el impacto de la vitamina E sobre la modulación del sistema inmune viene definido por factores tales como la edad y la relación dosis-respuesta. En broiler la inclusión en la dieta de niveles moderadamente superiores (25-50 UI/kg dieta) al recomendado por el National Research Council (NRC, 1994; 10 UI/kg) aumenta los títulos de anticuerpos tras la vacunación (Friedman et al., 1998; Leshchinsky y Klasing, 2001; Lin y Chang, 2006). Sin embargo, niveles superiores a 150 UI/kg tienen un efecto supresor sobre la producción de anticuerpos (Koutsos y Klasing, 2008). En relación a la edad es importante determinar aquellos periodos o “ventanas” en los que es necesario estimular el sistema inmune (Kogut, 2009). Un periodo a considerar sería el de las dos primeras semanas de vida del pollo debido a la menor funcionalidad de macrófagos y heterófilos (Kogut, 2009). El presente trabajo tiene como objetivo evaluar el efecto del nivel de Vitamina E y la edad sobre la modulación de la respuesta inmune en pollos. Para ello se estudió el efecto de la inclusión de 40 y 160 ppm de vitamina E en la dieta sobre la expresión de la interleuquina 2 (IL 2), el interferón gamma (IFN γ) y el factor de crecimiento mielomonocítico (MGF) en el bazo de los animales a los 7 y 21 días de edad

Anthropogenic ecosystem disturbance and the recovery debt

Ecosystem recovery from anthropogenic disturbances, either without human intervention or assisted by ecological restoration, is increasingly occurring worldwide. As ecosystems progress through recovery, it is important to estimate any resulting deficit in biodiversity and functions. Here we use data from 3,035 sampling plots worldwide, to quantify the interim reduction of biodiversity and functions occurring during the recovery process (that is, the 'recovery debt'). Compared with reference levels, recovering ecosystems run annual deficits of 46-51% for organism abundance, 27-33% for species diversity, 32-42% for carbon cycling and 31-41% for nitrogen cycling. Our results are consistent across biomes but not across degrading factors. Our results suggest that recovering and restored ecosystems have less abundance, diversity and cycling of carbon and nitrogen than 'undisturbed' ecosystems, and that even if complete recovery is reached, an interim recovery debt will accumulate. Under such circumstances, increasing the quantity of less-functional ecosystems through ecological restoration and offsetting are inadequate alternatives to ecosystem protection

Association of cooking patterns with inflammatory and cardio-metabolic risk biomarkers

Diet has been clearly associated with cardiovascular disease, but few studies focus on the influence of cooking and food preservation methods on health. The aim of this study was to describe cooking and food preservation patterns, as well as to examine their association with inflammatory and cardio-metabolic biomarkers in the Spanish adult population. A cross-sectional study of 10, 010 individuals, representative of the Spanish population, aged 18 years or over was performed using data from the ENRICA study. Food consumption data were collected through a face-to-face dietary history. Cooking and food preservation patterns were identified by factor analysis with varimax rotation. Linear regression models adjusted for main confounders were built. Four cooking and food preservation patterns were identified. The Spanish traditional pattern (positively correlated with boiling and sautéing, brining, and light frying) tends to be cardio-metabolically beneficial (with a reduction in C-reactive protein (-7.69%)), except for high density lipoprotein cholesterol (HDL-c), insulin levels, and anthropometrics. The health-conscious pattern (negatively correlated with battering, frying, and stewing) tends to improve renal function (with a reduction in urine albumin (-9.60%) and the urine albumin/creatinine ratio (-4.82%)). The youth-style pattern (positively correlated with soft drinks and distilled alcoholic drinks and negatively with raw food consumption) tends to be associated with good cardio-metabolic health except, for lower HDL-c (-6.12%), higher insulin (+6.35%), and higher urine albumin (+27.8%) levels. The social business pattern (positively correlated with the consumption of fermented alcoholic drinks, food cured with salt or smoke, and cured cheese) tends to be detrimental for the lipid profile (except HDL-c), renal function (urine albumin +8.04%), diastolic blood pressure (+2.48%), and anthropometrics. Cooking and food preservation patterns showed a relationship with inflammatory and cardio-metabolic health biomarkers. The Spanish traditional pattern and the health-conscious pattern were associated with beneficial effects on health and should be promoted. The youth-style pattern calls attention to some concerns, and the social business pattern was the most detrimental one. These findings support the influence of cooking and preservation patterns on health

Effectiveness of steroids versus placebo in preventing upper airway obstruction after extubation in critically ill children: rationale and design of a multicentric, double-blind, randomized study

BACKGROUND: Post-extubation upper airway obstruction (UAO) is a frequent complication causing stridor and respiratory distress, which occasionally require reintubation, thereby increasing morbidity and mortality rates. Contradictory results have been obtained in studies assessing the effectiveness of steroids in preventing post-extubation UAO, and the available evidence is limited. We designed a multicentric randomized, placebo-controlled study to explore the effectiveness of dexamethasone in preventing post-extubation UAO in children. METHODS: A multicentric, prospective, double-blind, randomized, placebo-controlled, phase IV clinical trial has been designed. The sample will include pediatric patients who are between 1 month and 16 years of age and who have been intubated for more than 48 h. Patients who have airway disorders or who have received steroids within the previous seven days will be excluded. Patients will be randomly assigned to receive either placebo or a therapy with dexamethasone 0.25 mg/kg every 6 h to be started 6 to 12 h prior to extubation (to a total of four doses). Randomization will be performed at a 1:1 ratio. Follow-up of patients will be carried out for 48 h after extubation. The main objective of this study is to access the reduction in the incidence of moderate to severe UAO symptoms following extubation. Secondary objectives include assessing the decrease in the incidence of reintubation, evaluating the use of additional therapies for UAO, and monitoring potential side effects of dexamethasone. DISCUSSION: The results of this study will contribute to the existing evidence on prophylaxis for post-extubation airway obstruction. TRIAL REGISTRATION: EudraCT identifier: 2009-016596-30. Registered on May 11, 2010

Spontaneous alloying in binary metal microclusters - A molecular dynamics study -

Microcanonical molecular dynamics study of the spontaneous alloying(SA), which is a manifestation of fast atomic diffusion in a nano-sized metal cluster, is done in terms of a simple two dimensional binary Morse model. Important features observed by Yasuda and Mori are well reproduced in our simulation. The temperature dependence and size dependence of the SA phenomena are extensively explored by examining long time dynamics. The dominant role of negative heat of solution in completing the SA is also discussed. We point out that a presence of melting surface induces the diffusion of core atoms even if they are solid-like. In other words, the {\it surface melting} at substantially low temperature plays a key role in attaining the SA.Comment: 15 pages, 12 fgures, Submitted to Phys.Rev.

Quantification of inaccurate diagnosis of COPD in primary care medicine: An analysis of the COACH clinical audit

Background: Inaccurate diagnosis in COPD is a current problem with relevant consequences in terms of inefficient health care, which has not been thoroughly studied in primary care medicine. The aim of the present study was to evaluate the degree of inaccurate diagnosis in Primary Care in Spain and study the determinants associated with it. Methods: The Community Assessment of COPD Health Care (COACH) study is a national, observational, randomized, non-interventional, national clinical audit aimed at evaluating clinical practice for patients with COPD in primary care medicine in Spain. For the present analysis, a correct diagnosis was evaluated based on previous exposure and airway obstruction with and without the presence of symptoms. The association of patient-level and center-level variables with inaccurate diagnosis was studied using multivariate multilevel binomial logistic regression models. Results: During the study 4,307 cases from 63 centers were audited. The rate of inaccurate diagnosis was 82.4% (inter-regional range from 76.8% to 90.2%). Patient-related interventions associated with inaccurate diagnosis were related to active smoking, lung function evaluation, and specific therapeutic interventions. Center-level variables related to the availability of certain complementary tests and different aspects of the resources available were also associated with an inaccurate diagnosis. Conclusions: The prevalence data for the inaccurate diagnosis of COPD in primary care medicine in Spain establishes a point of reference in the clinical management of COPD. The descriptors of the variables associated with this inaccurate diagnosis can be used to identify cases and centers in which inaccurate diagnosis is occurring considerably, thus allowing for improvement

CB1 Cannabinoid Receptor is a Target for Neuroprotection in Light Induced Retinal Degeneration

In the last few years, an increasing interest in the neuroprotective effect of cannabinoidshas taken place. The aim of the present work was to study the effects of modulatingcannabinoid receptor 1 (CB1) in the context of light induced retinal degeneration (LIRD),using an animal model that resembles many characteristics of human age-related maculardegeneration (AMD) and other degenerative diseases of the outer retina. Sprague Dawleyrats (n = 28) were intravitreally injected in the right eye with either a CB1 agonist (ACEA), oran antagonist (AM251). Contralateral eyes were injected with respective vehicles ascontrols. Then, rats were subjected to continuous illumination (12,000 lux) for 24 h.Retinas from 28 animals were processed by GFAP-immunohistochemistry (IHC),TUNEL technique, Western blotting (WB), or qRT-PCR. ACEA-treated retinas showeda significantly lower number of apoptotic nuclei in the outer nuclear layer (ONL), lower levelsof activated Caspase-3 by WB, and lower levels of glial reactivity by both GFAP-IHC andWB. qRT-PCR revealed that ACEA significantly decreased the expression of Bcl-2 andCYP1A1. Conversely, AM251-treated retinas showed a higher number of apoptotic nucleiin the ONL, higher levels of activated Caspase-3 by WB, and higher levels of glial reactivityas determined by GFAP-IHC and WB. AM251 increased the expression of Bcl-2, Bad,Bax, Aryl hydrocarbon Receptor (AhR), GFAP, and TNFα. In summary, the stimulation ofthe CB1 receptor, previous to the start of the pathogenic process, improved the survival ofphotoreceptors exposed to LIRD. The modulation of CB1 activity may be used as aneuroprotective strategy in retinal degeneration and deserves further studiesFil: Soliño, Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Larráyoz, Ignacio M.. Center For Biomedical Research Of La Rioja; EspañaFil: Lopez, Ester Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Rey Funes, Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Bareiro, Nidia Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Loidl, Cesar Fabian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Girardi, Elena Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Caltana, Laura Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Brusco, Herminia Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Martinez, Alfredo. Center For Biomedical Research Of La Rioja; EspañaFil: López, Juan José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentin

Duality and Universality for the Chern-Simons bosons

By mapping the relativistic version of the Chern-Simons-Landau-Ginzburg theory in 2+1 dimensions to the 3D lattice Villain x-y model coupled with the Chern-Simons gauge field, we investigate phase transitions of Chern-Simons bosons in the limit of strong coupling. We construct algebraically exact duality and flux attachment transformations of the lattice theories, corresponding to analogous transformations in the continuum limit. These transformations are used to convert the model with arbitrary fractional Chern-Simons coefficient $\alpha$ to a model with $\alpha$ either zero or one. Depending on this final value of $\alpha$, the phase transition in the original model is either in the universality class of the 3D x-y model or a ``fermionic'' universality class, unless the irrelevant corrections of cubic and higher power in momenta render the transition of the first order.Comment: 14 two-column pages, revtex 3.0, multicol and epsf.sty (optional), one PostScript figure, Submitted to Phys. Rev. B The changes intended to simplify the arguments and eliminate logical gaps. We also show how the filling factor $\nu$ is changed by the duality transformatio