In Vitro Surfactant and Perfluorocarbon Aerosol Deposition in a Neonatal Physical Model of the Upper Conducting Airways

Objective: Aerosol delivery holds potential to release surfactant or perfluorocarbon (PFC) to the lungs of neonates with respiratory distress syndrome with minimal airway manipulation. Nevertheless, lung deposition in neonates tends to be very low due to extremely low lung volumes, narrow airways and high respiratory rates. In the present study, the feasibility of enhancing lung deposition by intracorporeal delivery of aerosols was investigated using a physical model of neonatal conducting airways. Methods: The main characteristics of the surfactant and PFC aerosols produced by a nebulization system, including the distal air pressure and air flow rate, liquid flow rate and mass median aerodynamic diameter (MMAD), were measured at different driving pressures (4-7 bar). Then, a three-dimensional model of the upper conducting airways of a neonate was manufactured by rapid prototyping and a deposition study was conducted. Results: The nebulization system produced relatively large amounts of aerosol ranging between 0.3 +/- 0.0 ml/min for surfactant at a driving pressure of 4 bar, and 2.0 +/- 0.1 ml/min for distilled water (H(2)Od) at 6 bar, with MMADs between 2.61 +/- 0.1 mu m for PFD at 7 bar and 10.18 +/- 0.4 mu m for FC-75 at 6 bar. The deposition study showed that for surfactant and H(2)Od aerosols, the highest percentage of the aerosolized mass (similar to 65%) was collected beyond the third generation of branching in the airway model. The use of this delivery system in combination with continuous positive airway pressure set at 5 cmH(2)O only increased total airway pressure by 1.59 cmH(2)O at the highest driving pressure (7 bar). Conclusion: This aerosol generating system has the potential to deliver relatively large amounts of surfactant and PFC beyond the third generation of branching in a neonatal airway model with minimal alteration of pre-set respiratory support.

Morphofunctional changes in a rat model of Parkinson's disease - Effects of neurotrophic factors administration

255 p.

A model of the pelagic ecossystem in the eastern tropical Pacific Ocean

English: Recent calls for a more holistic approach to fisheries management have motivated development of trophic mass-balance models of ecosystems that underlie fisheries production. We developed a model hypothesis of the pelagic ecosystem in the eastern tropical Pacific Ocean (ETP) to gain insight into the relationships among the various species in the system and to explore the ecological implications of alternative methods of harvesting tunas. We represented the biomasses of and fluxes between the principal elements in the ecosystem with Ecopath, and examined the ecosystem's dynamic, time-series behavior with Ecosim. We parameterized the model for 38 species or groups of species, and described the sources, justifications, assumptions, and revisions of our estimates of the various parameters, diet relations, fisheries landings, and fisheries discards in the model. We conducted sensitivity analyses with an intermediate version of the model, for both the Ecopath mass-balance and the dynamic trajectories predicted by Ecosim. The analysis showed that changes in the basic parameters for two components at middle trophic levels, Cephalopods and Auxis spp., exert the greatest influence on the system. When the Cephalopod Q/B and Auxis spp. P/B were altered from their initial values and the model was rebalanced, the trends of the biomass trajectories predicted by Ecosim were not sensitive, but the scaling was sensitive for several components. We described the review process the model was subjected to, which included reviews by the IATTC Purse-seine Bycatch Working Group and by a working group supported by the National Center for Ecological Analysis and Synthesis. We fitted the model to historical time series of catches per unit of effort and mortality rates for yellowfin and bigeye tunas in simulations that incorporated historical fishing effort and a climate driver to represent the effect of El Niño-Southern Oscillation-scale variation on the system. The model was designed to evaluate the possible ecological implications of fishing for tunas in various ways. We recognize that a model cannot possibly represent all the complexity of a pelagic ocean ecosystem, but we believe that the ETP model provides insight into the structure and function of the pelagic ETP. Spanish: Llamamientos recientes hacia un enfoque más holístico al ordenamiento de la pesca han motivado el desarrollo de modelos tróficos de balance de masas de los ecosistemas que sostienen la producción pesquera. Desarrollamos una hipótesis modelo del ecosistema pelágico en el Océano Pacífico oriental tropical (POT) con miras a mejorar los conocimientos de las relaciones entre las distintas especies en el sistema y explorar las implicaciones ecológicas de métodos alternativos de capturar atunes. Con Ecopath representamos las biomasas de los elementos principales en el ecosistema, y los flujos entre los mismos, y con Ecosim examinamos el comportamiento dinámico del ecosistema con el tiempo. Parametrizamos el modelo para 38 especies o grupos de especies (denominados “componentes” del modelo), y describimos las fuentes, justificaciones, supuestos, y revisiones de nuestras estimaciones de los distintos parámetros, relaciones basadas en dieta, capturas retenidas de las pesquerías, y descartes de las mismas en el modelo. Realizamos análisis de sensibilidad con una versión intermedia del modelo, para el balance de masas de Ecopath y las trayectorias dinámicas predichas por Ecosim también. El análisis demostró que cambios en los parámetros básicos para dos componentes en niveles tróficos medianos, Cefalópodos y Auxis spp., ejercieron la mayor influencia sobre el sistema. Cuando se alteraron el Q/B de los Cefalópodos y el P/B de los Auxis spp. de sus valores iniciales y se balanceó el modelo de nuevo, las tendencias de las trayectorias de la biomasa predichas por Ecosim no fueron sensibles, pero la escala fue sensible para varios componentes. Describimos el proceso de revisión al que fue sujeto el modelo, inclusive revisiones por el Grupo de Trabajo sobre Captura Incidental de la CIAT y un grupo de trabajo apoyado por el Centro Nacional para Síntesis y Análisis Ecológicos. Ajustamos el modelo a series de tiempo históricas de capturas por unidad de esfuerzo y tasas de mortalidad de atunes aleta amarilla y patudo en simulaciones que incorporaron esfuerzo de pesca histórico e impulsos climáticos para representar el efecto de variaciones a escala de El Niño-Oscilación del Sur sobre el sistema. El modelo fue diseñado para evaluar las posibles implicaciones ecológicas de la pesca atunera de varias formas. Reconocemos la imposibilidad de que el modelo represente toda la complejidad de un ecosistema oceánico pelágico, pero creemos que el modelo del POT mejora los conocimientos de la estructura y función del POT pelágico.

Increased antiparkinson efficacy of the combined administration of VEGF- and GDNF-loaded nanospheres in a partial lesion model of Parkinson's disease

Current research efforts are focused on the application of growth factors, such as glial cell line-derived neurotrophic factor (GDNF) and vascular endothelial growth factor (VEGF), as neuroregenerative approaches that will prevent the neurodegenerative process in Parkinson's disease. Continuing a previous work published by our research group, and with the aim to overcome different limitations related to growth factor administration, VEGF and GDNF were encapsulated in poly(lactic-co-glycolic acid) nanospheres (NS). This strategy facilitates the combined administration of the VEGF and GDNF into the brain of 6-hydroxydopamine (6-OHDA) partially lesioned rats, resulting in a continuous and simultaneous drug release. The NS particle size was about 200 nm and the simultaneous addition of VEGF NS and GDNF NS resulted in significant protection of the PC-12 cell line against 6-OHDA in vitro. Once the poly(lactic-co-glycolic acid) NS were implanted into the striatum of 6-OHDA partially lesioned rats, the amphetamine rotation behavior test was carried out over 10 weeks, in order to check for in vivo efficacy. The results showed that VEGF NS and GDNF NS significantly decreased the number of amphetamine-induced rotations at the end of the study. In addition, tyrosine hydroxylase immunohistochemical analysis in the striatum and the external substantia nigra confirmed a significant enhancement of neurons in the VEGF NS and GDNF NS treatment group. The synergistic effect of VEGF NS and GDNF NS allows for a reduction of the dose by half, and may be a valuable neurogenerative/neuroreparative approach for treating Parkinson's disease.

Sensitivity of angler benefit estimates from a model of recreational demand to the definition of the substitute sites considered by the angler

Fishery managers are mandated to understand the effects that environmental damage, fishery regulations, and habitat improvement projects have on the net benefits that recreational anglers derive from their sport. Since 1994, the National Marine Fisheries Service (NMFS) has worked to develop a consistent method for estimating net benefits through site choice models of recreational trip demand. In estimating net benefits with these models, there is a tradeoff between computational efficiency and angler behavior in reality. This article examines this tradeoff by considering the sensitivity of angler-welfare estimates for an increase in striped bass (Morone saxatalis) angling quality across choice sets with five travel distance cutoffs and compares those estimates to a model with an unrestricted choice set. This article shows that 95% confidence intervals for welfare estimates of an increase in the striped bass catch and keep rate overlap for all distance-based choice sets specified here.

Muscle wasting in myotonic dystrophies: a model of premature aging

Myotonic dystrophy type 1 (DM1 or Steinert's disease) and type 2 (DM2) are multisystem disorders of genetic origin. Progressive muscular weakness, atrophy and myotonia are the most prominent neuromuscular features of these diseases, while other clinical manifestations such as cardiomyopathy, insulin resistance and cataracts are also common. From a clinical perspective, most DM symptoms are interpreted as a result of an accelerated aging (cataracts, muscular weakness and atrophy, cognitive decline, metabolic dysfunction, etc.), including an increased risk of developing tumors. From this point of view, DM1 could be described as a progeroid syndrome since a notable age dependent dysfunction of all systems occurs. The underlying molecular disorder in DM1 consists of the existence of a pathological (CTG) triplet expansion in the 3' untranslated region (UTR) of the Dystrophia ll/Iyotonica Protein Kinase (DMPK) gene, whereas (CCTG)n repeats in the first intron of the Cellular Nucleic acid Binding Protein/Zinc Finger Protein 9 (CNBP/ZNF9) gene cause DM2. The expansions are transcribed into (CUG)n and (CCUG)n-containing RNA, respectively, which form secondary structures and sequester RNA binding proteins, such as the splicing factor muscleblind-like protein (MBNL), forming nuclear aggregates known as foci. Other splicing factors, such as CUGBP, are also disrupted, leading to a spliceopathy of a large number of downstream genes linked to the clinical features of these diseases. Skeletal muscle regeneration relies on muscle progenitor cells, known as satellite cells, which are activated after muscle damage, and which proliferate and differentiate to muscle cells, thus regenerating the damaged tissue. Satellite cell dysfunction seems to be a common feature of both age-dependent muscle degeneration (sarcopenia) and muscle wasting in DM and other muscle degenerative diseases. This review aims to describe the cellular, molecular and macrostructural processes involved in the muscular degeneration seen in DM patients, highlighting the similarities found with muscle aging.

A simulation model of the dynamics of Peruvian anchoveta (Engraulis ringens)

The article describes the key elements of a model simulating the dynamics of the anchoveta (Engraulis ringens) in the Peruvian upwelling system (4 degrees to 14 degrees South). This model, based on coupled differential equations, is parametrized mainly using empirical data and functional relationships presented in two volumes issued by ICLARM in 1987 and 1989, and may thus be viewed as test of the hypotheses presented therein. Results to date suggest that present knowledge of mechanisms controlling the anchoveta stock is essentially consistent, and sufficient to build a model reflecting essential features of the stock biomass and recruitment dynamics.