Adrenoceptors and intestinal fluid and electrolyte transport in the rat

Noradrenaline was found to significantly stimulate fluid and Na absorption across everted sacs of rat jejunum. Of a number of a1, and 2-adrenoceptor antagonists tested only prazosin significantly inhibited the stimulant effect of noradrenaline and further experiments revealed an antiabsorptive effect of prazosin alone. Theophylline reduced jejunal fluid and Na absorption and this effect was not reversed by 2-adrenoceptor stimulation in contrast to previous findings in vivo. Evidence suggests the everted sac preparation is not appropriate to the study of intestinal fluid and electrolyte transport. The investigation of Jejunal ion transport in vitro was continued using an Ussing chamber preparation. Selective 2-adrenoceptor stimulation was found to depress electrogenic anion secretion, as neurotoxin tetrodotoxin indicated that this was a direct epithelial effect. 2-adrenoceptor agonists have considerable therapeutic value as antisecretory agents and the model of rat jejunum in vitro represents a convenient experimental model for research in this area. The selective 2-adrenoceptor antagonist ICI 118551 decreased basal SCC and inhibited increases in SCC in response to isoprenaline or salbutamol indicating the presence of a 2-adrenoceptor mechanism mediating both secretory tone and increases in secretory processes. Many intestinal secretagogues elicit electrolyte secretion via the stimulation of intramural secretory nervous pathways. If these pathways involve the activation of 2-adrenoceptorsthe 2-adrenoceptor antagonists may be useful in the treatment of diarrhoeal diseases. A single pass lumen perfusion technique was used to investigate possible sympathetic tone over colonic fluid and electrolyte absorption in the rat colon in vivo. The technique employed appeared to lack the necessary resolution for this study and alternative approaches are discussed

Investigating viscous fluid flow in an internal mixer using computational fluid dynamics

This thesis presents an effective methodology for the generation of a simulation which can be used to increase the understanding of viscous fluid processing equipment and aid in their development, design and optimisation. The Hampden RAPRA Torque Rheometer internal batch twin rotor mixer has been simulated with a view to establishing model accuracies, limitations, practicalities and uses. As this research progressed, via the analyses several 'snap-shot' analysis of several rotor configurations using the commercial code Polyflow, it was evident that the model was of some worth and its predictions are in good agreement with the validation experiments, however, several major restrictions were identified. These included poor element form, high man-hour requirements for the construction of each geometry and the absence of the transient term in these models. All, or at least some, of these limitations apply to the numerous attempts to model internal mixes by other researchers and it was clear that there was no generally accepted methodology to provide a practical three-dimensional model which has been adequately validated. This research, unlike others, presents a full complex three-dimensional, transient, non-isothermal, generalised non-Newtonian simulation with wall slip which overcomes these limitations using unmatched ridding and sliding mesh technology adapted from CFX codes. This method yields good element form and, since only one geometry has to be constructed to represent the entire rotor cycle, is extremely beneficial for detailed flow field analysis when used in conjunction with user defined programmes and automatic geometry parameterisation (AGP), and improves accuracy for investigating equipment design and operation conditions. Model validation has been identified as an area which has been neglected by other researchers in this field, especially for time dependent geometries, and has been rigorously pursued in terms of qualitative and quantitative velocity vector analysis of the isothermal, full fill mixing of generalised non-Newtonian fluids, as well as torque comparison, with a relatively high degree of success. This indicates that CFD models of this type can be accurate and perhaps have not been validated to this extent previously because of the inherent difficulties arising from most real processes.

The experimental evaluation of the dynamics of fluid-loaded microplates

An experimental testing system for the study of the dynamic behavior of fluid-loaded rectangular micromachined silicon plates is designed and presented in this paper. In this experimental system, the base-excitation technique combined with pseudo-random signal and cross-correlation analysis is applied to test fluid-loaded microstructures. Theoretical model is also derived to reveal the mechanism of such an experimental system in the application of testing fluid-loaded microstructures. The dynamic experiments cover a series of testings of various microplates with different boundary conditions and dimensions, both in air and immersed in water. This paper is the first that demonstrates the ability and performances of base excitation in the application of dynamic testing of microstructures that involves a natural fluid environment. Traditional modal analysis approaches are used to evaluate natural frequencies, modal damping and mode shapes from the experimental data. The obtained experimental results are discussed and compared with theoretical predictions. This research experimentally determines the dynamic characteristics of the fluid-loaded silicon microplates, which can contribute to the design of plate-based microsystems. The experimental system and testing approaches presented in this paper can be widely applied to the investigation of the dynamics of microstructures and nanostructures.

Proteomic analysis of a noninvasive human model of acute inflammation and its resolution:the twenty-one day gingivitis model

The 21-day experimental gingivitis model, an established noninvasive model of inflammation in response to increasing bacterial accumulation in humans, is designed to enable the study of both the induction and resolution of inflammation. Here, we have analyzed gingival crevicular fluid, an oral fluid comprising a serum transudate and tissue exudates, by LC-MS/MS using Fourier transform ion cyclotron resonance mass spectrometry and iTRAQ isobaric mass tags, to establish meta-proteomic profiles of inflammation-induced changes in proteins in healthy young volunteers. Across the course of experimentally induced gingivitis, we identified 16 bacterial and 186 human proteins. Although abundances of the bacterial proteins identified did not vary temporally, Fusobacterium outer membrane proteins were detected. Fusobacterium species have previously been associated with periodontal health or disease. The human proteins identified spanned a wide range of compartments (both extracellular and intracellular) and functions, including serum proteins, proteins displaying antibacterial properties, and proteins with functions associated with cellular transcription, DNA binding, the cytoskeleton, cell adhesion, and cilia. PolySNAP3 clustering software was used in a multilayered analytical approach. Clusters of proteins that associated with changes to the clinical parameters included neuronal and synapse associated proteins.

Modelling a biochemical reaction with computational fluid dynamics

Earlier investigations (Cartland Glover et al., 2004) into the use of computational fluid dynamics (CFD) for the modelling of gas-liquid and gas-liquid-solid flow allowed a simple biochemical reaction model to be implemented. A single plane mesh was used to represent the transport and reaction of molasses, the mould Aspergillus niger and citric acid in a bubble column with a height to diameter aspect ratio of 20:1. Two specific growth rates were used to examine the impact that biomass growth had on the local solids concentration and the effect this had on the local hydrodynamics of the bubble column.

Breakage model development and application with CFD for predicting breakage of whey protein precipitate particles

Particle breakage due to fluid flow through various geometries can have a major influence on the performance of particle/fluid processes and on the product quality characteristics of particle/fluid products. In this study, whey protein precipitate dispersions were used as a case study to investigate the effect of flow intensity and exposure time on the breakage of these precipitate particles. Computational fluid dynamic (CFD) simulations were performed to evaluate the turbulent eddy dissipation rate (TED) and associated exposure time along various flow geometries. The focus of this work is on the predictive modelling of particle breakage in particle/fluid systems. A number of breakage models were developed to relate TED and exposure time to particle breakage. The suitability of these breakage models was evaluated for their ability to predict the experimentally determined breakage of the whey protein precipitate particles. A "power-law threshold" breakage model was found to provide a satisfactory capability for predicting the breakage of the whey protein precipitate particles. The whey protein precipitate dispersions were propelled through a number of different geometries such as bends, tees and elbows, and the model accurately predicted the mean particle size attained after flow through these geometries. © 2005 Elsevier Ltd. All rights reserved.

Hydrogen production by steam reforming of DME in a large scale CFB reactor. Part I:computational model and predictions

This study presents a computational fluid dynamic (CFD) study of Dimethyl Ether steam reforming (DME-SR) in a large scale Circulating Fluidized Bed (CFB) reactor. The CFD model is based on Eulerian-Eulerian dispersed flow and solved using commercial software (ANSYS FLUENT). The DME-SR reactions scheme and kinetics in the presence of a bifunctional catalyst of CuO/ZnO/Al2O3+ZSM-5 were incorporated in the model using in-house developed user-defined function. The model was validated by comparing the predictions with experimental data from the literature. The results revealed for the first time detailed CFB reactor hydrodynamics, gas residence time, temperature distribution and product gas composition at a selected operating condition of 300 °C and steam to DME mass ratio of 3 (molar ratio of 7.62). The spatial variation in the gas species concentrations suggests the existence of three distinct reaction zones but limited temperature variations. The DME conversion and hydrogen yield were found to be 87% and 59% respectively, resulting in a product gas consisting of 72 mol% hydrogen. In part II of this study, the model presented here will be used to optimize the reactor design and study the effect of operating conditions on the reactor performance and products.

Development of a physiologically-based pharmacokinetic model of the rat central nervous system

Central nervous system (CNS) drug disposition is dictated by a drug’s physicochemical properties and its ability to permeate physiological barriers. The blood–brain barrier (BBB), blood-cerebrospinal fluid barrier and centrally located drug transporter proteins influence drug disposition within the central nervous system. Attainment of adequate brain-to-plasma and cerebrospinal fluid-to-plasma partitioning is important in determining the efficacy of centrally acting therapeutics. We have developed a physiologically-based pharmacokinetic model of the rat CNS which incorporates brain interstitial fluid (ISF), choroidal epithelial and total cerebrospinal fluid (CSF) compartments and accurately predicts CNS pharmacokinetics. The model yielded reasonable predictions of unbound brain-to-plasma partition ratio (Kpuu,brain) and CSF:plasma ratio (CSF:Plasmau) using a series of in vitro permeability and unbound fraction parameters. When using in vitro permeability data obtained from L-mdr1a cells to estimate rat in vivo permeability, the model successfully predicted, to within 4-fold, Kpuu,brain and CSF:Plasmau for 81.5% of compounds simulated. The model presented allows for simultaneous simulation and analysis of both brain biophase and CSF to accurately predict CNS pharmacokinetics from preclinical drug parameters routinely available during discovery and development pathways.

Phytoestrogens modulate breast cancer resistance protein expression and function at the blood-cerebrospinal fluid barrier

PURPOSE: Breast cancer resistance protein (BCRP/ABCG2) is a drug efflux transporter expressed at the blood cerebrospinal fluid barrier (BCSFB), and influences distribution of drugs into the central nervous systems (CNS). Current inhibitors have failed clinically due to neurotoxicity. Novel approaches are needed to identify new modulators to enhance CNS delivery. This study examines 18 compounds (mainly phytoestrogens) as modulators of the expression/function of BCRP in an in vitro rat choroid plexus BCSFB model. METHODS: Modulators were initially subject to cytotoxicity (MTT) assessment to determine optimal non-toxic concentrations. Reverse-transcriptase PCR and confocal microscopy were used to identify the presence of BCRP in Z310 cells. Thereafter modulation of the intracellular accumulation of the fluorescent BCRP probe substrate Hoechst 33342 (H33342), changes in protein expression of BCRP (western blotting) and the functional activity of BCRP (membrane insert model) were assessed under modulator exposure. RESULTS: A 24 hour cytotoxicity assay (0.001 µM-1000 µM) demonstrated the majority of modulators possessed a cellular viability IC50 > 148 µM. Intracellular accumulation of H33342 was significantly increased in the presence of the known BCRP inhibitor Ko143 and, following a 24 hour pre-incubation, all modulators demonstrated statistically significant increases in H33342 accumulation (P < 0.001), when compared to control and Ko143. After a 24 hour pre-incubation with modulators alone, a 0.16-2.5-fold change in BCRP expression was observed for test compounds. The functional consequences of this were confirmed in a permeable insert model of the BCSFB which demonstrated that 17-β-estradiol, naringin and silymarin (down-regulators) and baicalin (up-regulator) can modulate BCRP-mediated transport function at the BCSFB. CONCLUSION: We have successfully confirmed the gene and protein expression of BCRP in Z310 cells and demonstrated the potential for phytoestrogen modulators to influence the functionality of BCRP at the BCSFB and thereby potentially allowing manipulation of CNS drug disposition.

Influence of reaction atmosphere (H2O, N2, H2, CO2, CO) on fluidized-bed fast pyrolysis of biomass using detailed tar vapor chemistry in computational fluid dynamics

Secondary pyrolysis in fluidized bed fast pyrolysis of biomass is the focus of this work. A novel computational fluid dynamics (CFD) model coupled with a comprehensive chemistry scheme (134 species and 4169 reactions, in CHEMKIN format) has been developed to investigate this complex phenomenon. Previous results from a transient three-dimensional model of primary pyrolysis were used for the source terms of primary products in this model. A parametric study of reaction atmospheres (H2O, N2, H2, CO2, CO) has been performed. For the N2 and H2O atmosphere, results of the model compared favorably to experimentally obtained yields after the temperature was adjusted to a value higher than that used in experiments. One notable deviation versus experiments is pyrolytic water yield and yield of higher hydrocarbons. The model suggests a not overly strong impact of the reaction atmosphere. However, both chemical and physical effects were observed. Most notably, effects could be seen on the yield of various compounds, temperature profile throughout the reactor system, residence time, radical concentration, and turbulent intensity. At the investigated temperature (873 K), turbulent intensity appeared to have the strongest influence on liquid yield. With the aid of acceleration techniques, most importantly dimension reduction, chemistry agglomeration, and in-situ tabulation, a converged solution could be obtained within a reasonable time (∼30 h). As such, a new potentially useful method has been suggested for numerical analysis of fast pyrolysis.

Eulerian model for the condensation of pyrolysis vapors in a water condenser

The paper presents the simulation of the pyrolysis vapors condensation process using an Eulerian approach. The condensable volatiles produced by the fast pyrolysis of biomass in a 100 g/h bubbling fluidized bed reactor are condensed in a water cooled condenser. The vapors enter the condenser at 500 °C, and the water temperature is 15 °C. The properties of the vapor phase are calculated according to the mole fraction of its individual compounds. The saturated vapor pressure is calculated for the vapor mixture using a corresponding states correlation and assuming that the mixture of the condensable compounds behave as a pure fluid. Fluent 6.3 has been used as the simulation platform, while the condensation model has been incorporated to the main code using an external user defined function. © 2011 American Chemical Society.

A compartmental CFD-PBM model of high shear wet granulation

The conventional, geometrically lumped description of the physical processes inside a high shear granulator is not reliable for process design and scale-up. In this study, a compartmental Population Balance Model (PBM) with spatial dependence is developed and validated in two lab-scale high shear granulation processes using a 1.9L MiPro granulator and 4L DIOSNA granulator. The compartmental structure is built using a heuristic approach based on computational fluid dynamics (CFD) analysis, which includes the overall flow pattern, velocity and solids concentration. The constant volume Monte Carlo approach is implemented to solve the multi-compartment population balance equations. Different spatial dependent mechanisms are included in the compartmental PBM to describe granule growth. It is concluded that for both cases (low and high liquid content), the adjustment of parameters (e.g. layering, coalescence and breakage rate) can provide a quantitative prediction of the granulation process.

Wound healing studies and interfacial phenomena:use and relevance of the corneal model

The interaction of the wound dressing as a biomaterial with the wound bed is the central issue of this chapter. The interfacial phenomenon that encompasses the biological and biochemical consequences that arise when a biomaterial is introduced to a host biological environment is discussed. A great deal can be learned from observations arising from the behaviour of biomaterials at other body sites; one particularly relevant body site in the context of wound healing is the anterior eye. The cornea, tear film and posterior surface of the contact lens provide an informative model of the parallel interface that exists between the chronic wound bed, wound fluid and the dressing biomaterial. © 2011 Woodhead Publishing Limited All rights reserved.

Geometrical optimization of a fast pyrolysis bubbling fluidized bed reactor using comutational fluid dynamics

This paper analyzes the physical phenomena that take place inside an 1 kg/h bubbling fluidized bed reactor located at Aston University and presents a geometrically modified version of it, in order to improve certain hydrodynamic and gas flow characteristics. The bed uses, in its current operation, 40 L/min of N2 at 520 °C fed through a distributor plate and 15 L/min purge gas stream, i.e., N2 at 20 °C, via the feeding tube. The Eulerian model of FLUENT 6.3 is used for the simulation of the bed hydrodynamics, while the k - ε model accounts for the effect of the turbulence field of one phase on the other. The three-dimensional simulation of the current operation of the reactor showed that a stationary bubble was formed next to the feeding tube. The size of the permanent bubble reaches up to the splash zone of the reactor, without any fluidizaton taking place underneath the feeder. The gas flow dynamics in the freeboard of the reactor is also analyzed. A modified version of the reactor is presented, simulated, and analyzed, together with a discussion on the impact of the flow dynamics on the fast pyrolysis of biomass. © 2010 American Chemical Society.

Eulerian-Lagrangian two phase debris flow model

The main objective of this work is to develop a quasi three-dimensional numerical model to simulate stony debris flows, considering a continuum fluid phase, composed by water and fine sediments, and a non-continuum phase including large particles, such as pebbles and boulders. Large particles are treated in a Lagrangian frame of reference using the Discrete Element Method, the fluid phase is based on the Eulerian approach, using the Finite Element Method to solve the depth-averaged Navier-Stokes equations in two horizontal dimensions. The particle’s equations of motion are in three dimensions. The model simulates particle-particle collisions and wall-particle collisions, taking into account that particles are immersed in a fluid. Bingham and Cross rheological models are used for the continuum phase. Both formulations provide very stable results, even in the range of very low shear rates. Bingham formulation is better able to simulate the stopping stage of the fluid when applied shear stresses are low. Results of numerical simulations have been compared with data from laboratory experiments on a flume-fan prototype. Results show that the model is capable of simulating the motion of big particles moving in the fluid flow, handling dense particulate flows and avoiding overlap among particles. An application to simulate debris flow events that occurred in Northern Venezuela in 1999 shows that the model could replicate the main boulder accumulation areas that were surveyed by the USGS. Uniqueness of this research is the integration of mud flow and stony debris movement in a single modeling tool that can be used for planning and management of debris flow prone areas.