37 resultados para SIMULATED GASTROINTESTINAL CONDITIONS


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We have conducted a detailed investigation into the absorption, metabolism and microflora-dependent transformation of hydroxytyrosol ( HT), tyrosol (TYR) and their conjugated forms, such as oleuropein (OL). Conjugated forms underwent rapid hydrolysis under gastric conditions, resulting in significant increases in the amount of free HT and TYR entering the small intestine. Both HT and TYR transferred across human Caco-2 cell monolayers and rat segments of jejunum and ileum and were subject to classic phase I/II biotransformation. The major metabolites identified were an O-methylated derivative of HT, glucuronides of HT and TYR and a novel glutathionylated conjugate of HT. In contrast, there was no absorption of OL in either model. However, OL was rapidly degraded by the colonic microflora resulting in the formation of HT. Our study provides additional information regarding the breakdown of complex olive oil polyphenols in the GI tract, in particular the stomach and the large intestine.

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This study investigates the production of alginate microcapsules, which have been coated with the polysaccharide chitosan, and evaluates some of their properties with the intention of improving the gastrointestinal viability of a probiotic (Bifidobacterium breve) by encapsulation in this system. The microcapsules were dried by a variety of methods, and the most suitable was chosen. The work described in this Article is the first report detailing the effects of drying on the properties of these microcapsules and the viability of the bacteria within relative to wet microcapsules. The pH range over which chitosan and alginate form polyelectrolyte complexes was explored by spectrophotometry, and this extended into swelling studies on the microcapsules over a range of pHs associated with the gastrointestinal tract. It was shown that chitosan stabilizes the alginate microcapsules at pHs above 3, extending the stability of the capsules under these conditions. The effect of chitosan exposure time on the coating thickness was investigated for the first time by confocal laser scanning microscopy, and its penetration into the alginate matrix was shown to be particularly slow. Coating with chitosan was found to increase the survival of B. breve in simulated gastric fluid as well as prolong its release upon exposure to intestinal pH.

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The effect of episodic drought on dissolved organic carbon (DOC) dynamics in peatlands has been the subject of considerable debate, as decomposition and DOC production is thought to increase under aerobic conditions, yet decreased DOC concentrations have been observed during drought periods. Decreased DOC solubility due to drought-induced acidification driven by sulphur (S) redox reactions has been proposed as a causal mechanism; however evidence is based on a limited number of studies carried out at a few sites. To test this hypothesis on a range of different peats, we carried out controlled drought simulation experiments on peat cores collected from six sites across Great Britain. Our data show a concurrent increase in sulphate (SO4) and a decrease in DOC across all sites during simulated water table draw-down, although the magnitude of the relationship between SO4 and DOC differed between sites. Instead, we found a consistent relationship across all sites between DOC decrease and acidification measured by the pore water acid neutralising capacity (ANC). ANC provided a more consistent measure of drought-induced acidification than SO4 alone because it accounts for differences in base cation and acid anions concentrations between sites. Rewetting resulted in rapid DOC increases without a concurrent increase in soil respiration, suggesting DOC changes were primarily controlled by soil acidity not soil biota. These results highlight the need for an integrated analysis of hydrologically driven chemical and biological processes in peatlands to improve our understanding and ability to predict the interaction between atmospheric pollution and changing climatic conditions from plot to regional and global scales.

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Background: The surface properties of probiotic bacteria influence to a large extent their interactions within the gut ecosystem. There is limited amount of information on the effect of the production process on the surface properties of probiotic lactobacilli in relation to the mechanisms of their adhesion to the gastrointestinal mucosa. The aim of this work was to investigate the effect of the fermentation pH and temperature on the surface properties and adhesion ability to Caco-2 cells of the probiotic strain Lactobacillus rhamnosus GG. Results: The cells were grown at pH 5, 5.5, 6 (temperature 37 °C) and at pH 6.5 (temperature 25 °C, 30 °C and 37 °C), and their surfaces analysed by X-ray photoelectron spectrometry (XPS), Fourier transform infrared spectroscopy (FT-IR) and gel-based proteomics. The results indicated that for all the fermentation conditions, with the exception of pH 5, a higher nitrogen to carbon ratio and a lower phosphate content was observed at the surface of the bacteria, which resulted in a lower surface hydrophobicity and reduced adhesion levels to Caco-2 cells as compared to the control fermentation (pH 6.5, 37 oC). A number of adhesive proteins, which have been suggested in previous published works to take part in the adhesion of bacteria to the human gastrointestinal tract, were identified by proteomic analysis, with no significant differences between samples however. Conclusions: The temperature and the pH of the fermentation influenced the surface composition, hydrophobicity and the levels of adhesion of L. rhamnosus GG to Caco-2 cells. It was deduced from the data that a protein rich surface reduced the adhesion ability of the cells.

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An analysis of observational data in the Barents Sea along a meridian at 33°30' E between 70°30' and 72°30' N has reported a negative correlation between El Niño/La Niña Southern Oscillation (ENSO) events and water temperature in the top 200 m: the temperature drops about 0.5 °C during warm ENSO events while during cold ENSO events the top 200 m layer of the Barents Sea is warmer. Results from 1 and 1/4-degree global NEMO models show a similar response for the whole Barents Sea. During the strong warm ENSO event in 1997–1998 an anomalous anticyclonic atmospheric circulation over the Barents Sea enhances heat loses, as well as substantially influencing the Barents Sea inflow from the North Atlantic, via changes in ocean currents. Under normal conditions along the Scandinavian peninsula there is a warm current entering the Barents Sea from the North Atlantic, however after the 1997–1998 event this current is weakened. During 1997–1998 the model annual mean temperature in the Barents Sea is decreased by about 0.8 °C, also resulting in a higher sea ice volume. In contrast during the cold ENSO events in 1999–2000 and 2007–2008, the model shows a lower sea ice volume, and higher annual mean temperatures in the upper layer of the Barents Sea of about 0.7 °C. An analysis of model data shows that the strength of the Atlantic inflow in the Barents Sea is the main cause of heat content variability, and is forced by changing pressure and winds in the North Atlantic. However, surface heat-exchange with the atmosphere provides the means by which the Barents sea heat budget relaxes to normal in the subsequent year after the ENSO events.

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Hamburg atmospheric general circulation model ECHAM3 at T106 resolution (1.125' lat.Aon.) has considerable skill in reproducing the observed seasonal reversal of mean sea level pressure, the location of the summer heat low as well as the position of the monsoon trough over the Indian subcontinent. The present-day climate and its seasonal cycle are realistically simulated by the model over this region. The model simulates the structure, intensity, frequency, movement and lifetime of monsoon depressions remarkably well. The number of monsoon depressions/storms simulated by the model in a year ranged from 5 to 12 with an average frequency of 8.4 yr-', not significantly different from the observed climatology. The model also simulates the interannual variability in the formation of depressions over the north Bay of Bengal during the summer monsoon season. In the warmer atmosphere under doubled CO2 conditions, the number of monsoon depressions/cyclonic storms forming in Indian seas in a year ranged from 5 to 11 with an average frequency of 7.6 yr-', not significantly different from those inferred in the control run of the model. However, under doubled CO2 conditions, fewer depressions formed in the month of June. Neither the lowest central pressure nor the maximum wind speed changes appreciably in monsoon depressions identified under simulated enhanced greenhouse conditions. The analysis suggests there will be no significant changes in the number and intensity of monsoon depressions in a warmer atmosphere.

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The objective of this work was to evaluate the feasibility of simulating maize yield in a sub‑tropical region of southern Brazil using the general large area model (Glam). A 16‑year time series of daily weather data were used. The model was adjusted and tested as an alternative for simulating maize yield at small and large spatial scales. Simulated and observed grain yields were highly correlated (r above 0.8; p<0.01) at large scales (greater than 100,000 km2), with variable and mostly lower correlations (r from 0.65 to 0.87; p<0.1) at small spatial scales (lower than 10,000 km2). Large area models can contribute to monitoring or forecasting regional patterns of variability in maize production in the region, providing a basis for agricultural decision making, and Glam‑Maize is one of the alternatives.

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Simulations of ozone loss rates using a three-dimensional chemical transport model and a box model during recent Antarctic and Arctic winters are compared with experimental loss rates. The study focused on the Antarctic winter 2003, during which the first Antarctic Match campaign was organized, and on Arctic winters 1999/2000, 2002/2003. The maximum ozone loss rates retrieved by the Match technique for the winters and levels studied reached 6 ppbv/sunlit hour and both types of simulations could generally reproduce the observations at 2-sigma error bar level. In some cases, for example, for the Arctic winter 2002/2003 at 475 K level, an excellent agreement within 1-sigma standard deviation level was obtained. An overestimation was also found with the box model simulation at some isentropic levels for the Antarctic winter and the Arctic winter 1999/2000, indicating an overestimation of chlorine activation in the model. Loss rates in the Antarctic show signs of saturation in September, which have to be considered in the comparison. Sensitivity tests were performed with the box model in order to assess the impact of kinetic parameters of the ClO-Cl2O2 catalytic cycle and total bromine content on the ozone loss rate. These tests resulted in a maximum change in ozone loss rates of 1.2 ppbv/sunlit hour, generally in high solar zenith angle conditions. In some cases, a better agreement was achieved with fastest photolysis of Cl2O2 and additional source of total inorganic bromine but at the expense of overestimation of smaller ozone loss rates derived later in the winter.

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A statistical–dynamical regionalization approach is developed to assess possible changes in wind storm impacts. The method is applied to North Rhine-Westphalia (Western Germany) using the FOOT3DK mesoscale model for dynamical downscaling and ECHAM5/OM1 global circulation model climate projections. The method first classifies typical weather developments within the reanalysis period using K-means cluster algorithm. Most historical wind storms are associated with four weather developments (primary storm-clusters). Mesoscale simulations are performed for representative elements for all clusters to derive regional wind climatology. Additionally, 28 historical storms affecting Western Germany are simulated. Empirical functions are estimated to relate wind gust fields and insured losses. Transient ECHAM5/OM1 simulations show an enhanced frequency of primary storm-clusters and storms for 2060–2100 compared to 1960–2000. Accordingly, wind gusts increase over Western Germany, reaching locally +5% for 98th wind gust percentiles (A2-scenario). Consequently, storm losses are expected to increase substantially (+8% for A1B-scenario, +19% for A2-scenario). Regional patterns show larger changes over north-eastern parts of North Rhine-Westphalia than for western parts. For storms with return periods above 20 yr, loss expectations for Germany may increase by a factor of 2. These results document the method's functionality to assess future changes in loss potentials in regional terms.

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The response of ten atmospheric general circulation models to orbital forcing at 6 kyr BP has been investigated using the BIOME model, which predicts equilibrium vegetation distribution, as a diagnostic. Several common features emerge: (a) reduced tropical rain forest as a consequence of increased aridity in the equatorial zone, (b) expansion of moisture-demanding vegetation in the Old World subtropics as a consequence of the expansion of the Afro–Asian monsoon, (c) an increase in warm grass/shrub in the Northern Hemisphere continental interiors in response to warming and enhanced aridity, and (d) a northward shift in the tundra–forest boundary in response to a warmer growing season at high northern latitudes. These broadscale features are consistent from model to model, but there are differences in their expression at a regional scale. Vegetation changes associated with monsoon enhancement and high-latitude summer warming are consistent with palaeoenvironmental observations, but the simulated shifts in vegetation belts are too small in both cases. Vegetation changes due to warmer and more arid conditions in the midcontinents of the Northern Hemisphere are consistent with palaeoenvironmental data from North America, but data from Eurasia suggests conditions were wetter at 6 kyr BP than today. The models show quantitatively similar vegetation changes in the intertropical zone, and in the northern and southern extratropics. The small differences among models in the magnitude of the global vegetation response are not related to differences in global or zonal climate averages, but reflect differences in simulated regional features. Regional-scale analyses will therefore be necessary to identify the underlying causes of such differences among models.

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New compilations of African pollen and lake data are compared with climate (CCM1, NCAR, Boulder) and vegetation (BIOME 1.2, GSG, Lund) simulations for the last glacial maximum (LGM) and early to mid-Holocene (EMH). The simulated LGM climate was ca 4°C colder and drier than present, with maximum reduction in precipitation in semi-arid regions. Biome simulations show lowering of montane vegetation belts and expansion of southern xerophytic associations, but no change in the distribution of deserts and tropical rain forests. The lakes show LGM conditions similar or drier than present throughout northern and tropical Africa. Pollen data indicate lowering of montane vegetation belts, the stability of the Sahara, and a reduction of rain forest. The paleoenvironmental data are consistent with the simulated changes in temperature and moisture budgets, although they suggest the climate model underestimates equatorial aridity. EMH simulations show temperatures slightly less than present and increased monsoonal precipitation in the eastern Sahara and East Africa. Biome simulations show an upward shift of montane vegetation belts, fragmentation of xerophytic vegetation in southern Africa, and a major northward shift of the southern margin of the eastern Sahara. The lakes indicate conditions wetter than present across northern Africa. Pollen data show an upward shift of the montane forests, the northward shift of the southern margin of the Sahara, and a major extension of tropical rain forest. The lake and pollen data confirm monsoon expansion in eastern Africa, but the climate model fails to simulate the wet conditions in western Africa.

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Live bacterial cells (LBC) are administered orally as attenuated vaccines, to deliver biopharmaceutical agents, and as probiotics to improve gastrointestinal health. However, LBC present unique formulation challenges and must survive gastrointestinal antimicrobial defenses including gastric acid after administration. We present a simple new formulation concept, termed Polymer Film Laminate (PFL). LBC are ambient dried onto cast acid-resistant enteric polymer films that are then laminated together to produce a solid oral dosage form. LBC of a model live bacterial vaccine and a probiotic were dried directly onto a cast film of enteric polymer. The effectiveness at protecting dried cells in a simulated gastric fluid (pH 2.0) depended on the composition of enteric polymer film used, with a blend of ethylcellulose plus Eudragit L100 55 providing greater protection from acid than Eudragit alone. However, although PFL made from blended polymers films completely released low molecular weight dye into intestinal conditions (pH 7.0), they failed to release LBC. In contrast, PFL made from Eudragit alone successfully protected dried probiotic or vaccine LBC from simulated gastric fluid for 2h, and subsequently released all viable cells within 60min of transfer into simulated intestinal fluid. Release kinetics could be controlled by modifying the lamination method.

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A set of high-resolution radar observations of convective storms has been collected to evaluate such storms in the UK Met Office Unified Model during the DYMECS project (Dynamical and Microphysical Evolution of Convective Storms). The 3-GHz Chilbolton Advanced Meteorological Radar was set up with a scan-scheduling algorithm to automatically track convective storms identified in real-time from the operational rainfall radar network. More than 1,000 storm observations gathered over fifteen days in 2011 and 2012 are used to evaluate the model under various synoptic conditions supporting convection. In terms of the detailed three-dimensional morphology, storms in the 1500-m grid-length simulations are shown to produce horizontal structures a factor 1.5–2 wider compared to radar observations. A set of nested model runs at grid lengths down to 100m show that the models converge in terms of storm width, but the storm structures in the simulations with the smallest grid lengths are too narrow and too intense compared to the radar observations. The modelled storms were surrounded by a region of drizzle without ice reflectivities above 0 dBZ aloft, which was related to the dominance of ice crystals and was improved by allowing only aggregates as an ice particle habit. Simulations with graupel outperformed the standard configuration for heavy-rain profiles, but the storm structures were a factor 2 too wide and the convective cores 2 km too deep.

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In most in vitro studies of oral drug permeability, little attempt is made to reproduce the gastrointestinal lumenal environment. The aim of this study was to evaluate the compatibility of simulated intestinal fluid (SIF) solutions with Caco-2 cell monolayers and Ussing chamber-mounted rat ileum under standard permeability experiment protocols. In preliminary experiments, fasted-state simulated intestinal fluid (FaSSIF) and fed-state simulated intestinal fluid (FeSSIF) solutions based on the dissolution medium formulae of Dressman and co-workers (1998) were modified for compatibility with Caco-2 cells to produce FaS-SIF and FeSSIF "transport" solutions for use with in vitro permeability models. For Caco-2 cells exposed to FaSSIF and FESSIF transport solutions, the transepithelial electrical resistance was maintained for over 4 h and mannitol permeability was equivalent to that in control (Hank's Balanced Salt Solution-treated) cell layers. Scanning electron microscopy revealed that microvilli generally maintained a normal distribution, although some shortening of microvilli and occasional small areas of denudation were observed. For rat ileum in the Ussing chambers, the potential difference (PD) collapsed to zero over 120 min when exposed to the FaSSIF transport solution and an even faster collapse of the PD was observed when the FeSSIF transport solution was used. Electron micrographs revealed erosion of the villi tips and substantial denudation of the microvilli after exposure of ileal tissue to FaSSIF and FeSSIF solutions, and permeability to mannitol was increased by almost two-fold. This study indicated that FaSSIF and FeSSIF transport solutions can be used with Caco-2 monolayers to evaluate drug permeability, but rat ileum in Ussing chambers is adversely affected by these solutions. Metoprolol permeability in Caco-2 experiments was reduced by 33% using the FaSSIF and 75% using the FeSSIF compared to permeability measured using HBSS. This illustrates that using physiological solutions can influence permeability measurements.

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The climate over the Arctic has undergone changes in recent decades. In order to evaluate the coupled response of the Arctic system to external and internal forcing, our study focuses on the estimation of regional climate variability and its dependence on large-scale atmospheric and regional ocean circulations. A global ocean–sea ice model with regionally high horizontal resolution is coupled to an atmospheric regional model and global terrestrial hydrology model. This way of coupling divides the global ocean model setup into two different domains: one coupled, where the ocean and the atmosphere are interacting, and one uncoupled, where the ocean model is driven by prescribed atmospheric forcing and runs in a so-called stand-alone mode. Therefore, selecting a specific area for the regional atmosphere implies that the ocean–atmosphere system can develop ‘freely’ in that area, whereas for the rest of the global ocean, the circulation is driven by prescribed atmospheric forcing without any feedbacks. Five different coupled setups are chosen for ensemble simulations. The choice of the coupled domains was done to estimate the influences of the Subtropical Atlantic, Eurasian and North Pacific regions on northern North Atlantic and Arctic climate. Our simulations show that the regional coupled ocean–atmosphere model is sensitive to the choice of the modelled area. The different model configurations reproduce differently both the mean climate and its variability. Only two out of five model setups were able to reproduce the Arctic climate as observed under recent climate conditions (ERA-40 Reanalysis). Evidence is found that the main source of uncertainty for Arctic climate variability and its predictability is the North Pacific. The prescription of North Pacific conditions in the regional model leads to significant correlation with observations, even if the whole North Atlantic is within the coupled model domain. However, the inclusion of the North Pacific area into the coupled system drastically changes the Arctic climate variability to a point where the Arctic Oscillation becomes an ‘internal mode’ of variability and correlations of year-to-year variability with observational data vanish. In line with previous studies, our simulations provide evidence that Arctic sea ice export is mainly due to ‘internal variability’ within the Arctic region. We conclude that the choice of model domains should be based on physical knowledge of the atmospheric and oceanic processes and not on ‘geographic’ reasons. This is particularly the case for areas like the Arctic, which has very complex feedbacks between components of the regional climate system.