A new method to model change in cutaneous blood flow due to mechanical skin irritation part I: comparison between experimental and numerical data

Mechanical skin irritation creates vasodilation. Vasodilation of vascular networks induces increase in blood volume and blood velocity. Both can be measured by Laser Doppler Velocimetry. We propose in this article a method permitting comparison between experimental and numerical results. Experimental data was obtained by Laser Doppler Velocimetry. Numerical results were obtained by a continuous model of the vascular network. The model consists of three layers. First and last layer are described by anisotropic and heterogeneous porous media. They represent the irrigation and the drainage of the vascular system. The intermediate layer is described by a lumped parameter model that does not permit horizontal fluxes. All vessels are compliant. The permeabilities depend on the volumes of the specific layer. Skin irritation is modeled by a change in compliance of small arterial blood vessels. The comparison between experimental and numerical data is based on the model proposed by Bonner and Nossal [1981. Model for laser Doppler measurements of blood flow. Appl. Opt. 20, 2097-2107]. The model describes the Doppler frequency spectrum S(omega) as a function of the optical phenomena creating the frequency shift. The comparison is based on the model of the first moment M1 approximately integralomegaS(omega)domega. The variables of the first moment can be determined by results of the numerical model. We have shown, that it exists a linear relation between the change in compliance and the following increase in first moment. Using this linear relation experimental and numerical data can be compared.     

First phase microcirculatory reaction to mechanical skin irritation: a three layer model of a compliant vascular tree

Mechanical skin irritation creates vasodilatation in the line of a stroke and in the surrounding tissue. To obtain further insight on underlying physiological mechanisms we developed a model of the vascular network comprised of three layers, where the first and the last one have a tree structure. They represent the arterial and the venous system, respectively. Both are connected via an intermediate zone representing the core of the microcirculation, which is described by means of a compliant compartment model. Irritation induces change in compliance of vessels situated at the entrance of the intermediate zone. Thus the model describes flow and pressure behavior due to mechanical skin irritation.     

Potentiation of epithelial innate host responses by intercellular communication

The epithelium efficiently attracts immune cells upon infection despite the low number of pathogenic microbes and moderate levels of secreted chemokines per cell. Here we examined whether horizontal intercellular communication between cells may contribute to a coordinated response of the epithelium. Listeria monocytogenes infection, transfection, and microinjection of individual cells within a polarized intestinal epithelial cell layer were performed and activation was determined at the single cell level by fluorescence microscopy and flow cytometry. Surprisingly, chemokine production after L. monocytogenes infection was primarily observed in non-infected epithelial cells despite invasion-dependent cell activation. Whereas horizontal communication was independent of gap junction formation, cytokine secretion, ion fluxes, or nitric oxide synthesis, NADPH oxidase (Nox) 4-dependent oxygen radical formation was required and sufficient to induce indirect epithelial cell activation. This is the first report to describe epithelial cell-cell communication in response to innate immune activation. Epithelial communication facilitates a coordinated infectious host defence at the very early stage of microbial infection.     

Mucoadhesive bilayered tablets for buccal sustained release of flurbiprofen

The aim of this work was the design of sustained-release mucoadhesive bilayered tablets, using mixtures of mucoadhesive polymers and an inorganic matrix (hydrotalcite), for the topical administration of flurbiprofen in the oral cavity. The first layer, responsible for the tablet retention on the mucosa, was prepared by compression of a cellulose derivative and polyacrylic derivative blend. The second layer, responsible for buccal drug delivery, was obtained by compression of a mixture of the same (first layer) mucoadhesive polymers and hydrotalcite containing flurbiprofen. Nonmedicated tablets were evaluated in terms of swelling, mucosal adhesion, and organoleptic characteristics; in vitro and in vivo release studies of flurbiprofen-loaded tablets were performed as well. The best results were obtained from the tablets containing 20 mg of flurbiprofen, which allowed a good anti-inflammatory sustained release in the buccal cavity for 12 hours, ensuring efficacious salivary concentrations, and led to no irritation. This mucoadhesive formulation offers many advantages over buccal lozenges because it allows for reduction in daily administrations and daily drug dosage and is suitable for the treatment of irritation, pain, and discomfort associated with gingivitis, sore throats, laryngopharyngitis, cold, and periodontal surgery. Moreover, it adheres well to the gum and is simple to apply, which means that patient compliance is improved. Published: July 13, 2007     

Effects of sedimentation of small red blood cell aggregates on blood flow in narrow horizontal tubes

The flow properties of aggregating red cell suspensions flowing at low flow rates through horizontal tubes are analyzed using a theoretical model. The effects of sedimentation of small aggregates, which will be formed at comparatively high flow rates, on the relative apparent viscosity are considered. In the case in which a large number of small aggregates are formed in a suspension flowing through a horizontal tube, it seems that red cells are transported as a concentrated suspension through the bottom part of the tube because of sedimentation of aggregates. A two-layer flow model is used for the distribution of red cells. It consists of plasma in the upper part and a concentrated red cell suspension in the bottom part of the tube divided by a smooth and horizontal interface. It is assumed that the suspension is a Newtonian fluid whose viscosity increases exponentially with hematocrit. The velocity distribution, the relative apparent viscosity and the flux of red cells are calculated as functions of width of plasma layer for a different discharge hematocrit. The theoretical results are compared with the results obtained from experimental data. The relative apparent viscosity increases rapidly with an increasing degree of sedimentation over a wide range of plasma layer widths.     

Integrating fluxes from heterogeneous vegetation

The vegetated landscape of Europe has been strongly impacted by human management to produce a heterogeneous patchwork of semi‐natural and agricultural vegetation varying over a wide range of spatial scales. A model is described for averaging vegetation fluxes from a landscape of forest and grassland into the planetary boundary layer (PBL). At a scale of 1 km, model simulations indicate that vegetation heterogeneity exerts little effect on the PBL and regional fluxes will be simple areal averages of the different vegetation types. Above 5 km the model simulates significant effects of different vegetation types on the whole PBL. Averaging fluxes to the regional scale will therefore need to consider explicitly the nature, extent and behaviour of different vegetation types.     

Computer model of unstirred layer and intracellular pH changes. Determinants of unstirred layer pH

Transmembrane acid–base fluxes affect the intracellular pH and unstirred layer pH around a superfused biological preparation. In this paper the factors influencing the unstirred layer pH and its gradient are studied. An analytical expression of the unstirred layer pH gradient in steady state is derived as a function of simultaneous transmembrane fluxes of (weak) acids and bases with the dehydration reaction of carbonic acid in equilibrium. Also a multicompartment computer model is described consisting of the extracellular bulk compartment, different unstirred layer compartments and the intracellular compartment. With this model also transient changes and the influence of carbonic anhydrase (CA) can be studied. The analytical expression and simulations with the multicompartment model demonstrate that in steady state the unstirred layer pH and its gradient are influenced by the size and type of transmembrane flux of acids and bases, their dissociation constant and diffusion coefficient, the concentration, diffusion coefficient and type of mobile buffers and the activity and location of CA. Similar principles contribute to the amplitude of the unstirred layer pH transients. According to these models an immobile buffer does not influence the steady-state pH, but reduces the amplitude of pH transients especially when these are fast. The unstirred layer pH provides useful information about transmembrane acid–base fluxes. This paper gives more insight how the unstirred layer pH and its transients can be interpreted. Methodological issues are discussed.     

Mucus clearance by two-phase gas-liquid flow mechanism: asymmetric periodic flow model

Mucus transport by two-phase gas-liquid flow mechanism was investigated with in vitro flow models under asymmetric periodic airflow conditions with nine different liquid solutions with rheological properties similar to human sputum. The flow model was made with 1.0-cm-ID glass tube and positioned either vertically or horizontally. With a constant supply of the test liquids into the model tube (0.5 ml/min), the liquid layer transport speed (LLTS) as well as the mean liquid layer thickness at steady-state condition (hs) was measured in conjunction with various airflow patterns of different expiratory and inspiratory flow rate, breathing frequency (f), and tidal volume (VT). The flow patterns were maintained within the range of normal breathing. In the horizontal tube model, LLTS ranged from 1.14 +/- 0.02 to 3.39 +/- 0.04 cm/min at the peak expiratory flow rate (VEp) of 30-60 l/min. The inspiratory flow rate, as well as f and VT did not affect LLTS. However, LLTS increased with increasing VEp, and at the same VEp LLTS was higher with viscoelastic than with viscous liquid. In the vertical tube model, the upward transport of mucus could not be achieved at VEp lower than 30 l/min particularly with low viscosity and low elasticity fluid. However, at high values of VEp, LLTS was comparable to that in the horizontal tube model with viscoelastic fluid, whereas LLTS of viscous liquid showed 26-40% lower than that in the horizontal tube model. The value of hs was 5-20% of the tube diameter at VEp of 30-60 l/min in both models. These results indicate that effective mucus clearance can be achieved by two-phase gas-liquid flow mechanism in patients with excessive bronchial secretions with biased tidal breathing favoring the expiratory flow and that the clearance can be further promoted by changing rheological properties of mucus.     

PSYCHOPHYSICAL PROPERTIES OF MECHANICAL ORAL IRRITATION

A number of commonly consumed fruits and vegetables (e.g., kiwifruit, pineapple and taro) cause oral irritation, and there is anecdotal evidence that this influences the acceptability of such products. In each of these foods, oral irritation is produced by free crystalline calcium oxalate (raphides). The psychophysics of the mechanical oral irritation caused by raphides was studied in two experiments using a model system based on kiwifruit. In the first experiment, the location of irritant sensations and perceived intensity of the irritation caused by suspensions of raphides were determined using a ten-member trained sensory panel. Stinging and numbing were found to increase significantly with increasing concentrations of raphides. Stinging occurred principally on the tongue as well as in the throat and numbing principally on the tongue. The number of oral areas irritated was shown to increase with raphide concentration and to decrease over a 60-min period. In the second experiment, sugars (fructose, sucrose, glucose and inositol), acids (citric, malic and quinic) and an enzyme (actinidin) were added to the model to examine interactions between these chemical stimuli and the mechanical action of the raphides. Addition of acids to the model was shown to enhance irritation in addition to increasing sourness and suppressing sweetness. The addition of actinidin had no significant effects on irritation or tastes. It is suggested that acidity may aggravate irritation at low raphide concentration, but beyond a critical level of mechanical irritation the presence of acids has little additional effect. These results provide the first detailed data of the psychophysics of mechanical oral irritation in food, and have important implications for producing foods with lower levels of irritation and increased acceptability.     

Coupling of Solute and Solvent Flows in Porous Lipid Bilayer Membranes

The present experiments were designed to evaluate coupling of water and nonelectrolyte flows in porous lipid bilayer membranes (i.e., in the presence of amphotericin B) in series with unstirred layers. Alterations in solute flux during osmosis, with respect to the flux in the absence of net water flow, could be related to two factors: first, changes in the diffusional component of solute flux referable to variations in solute concentrations at the membrane interfaces produced by osmotic flow through the unstirred layers; and second, coupling of solute and solvent flows within the membrane phase. Osmotic water flow in the same direction as solute flow increased substantially the net fluxes of glycerol and erythritol through the membranes, while osmotic flow in the opposite direction to glycerol flow reduced the net flux of that solute. The observed effects of osmotic water flow on the fluxes of these solutes were in reasonable agreement with predictions based on a model for coupling of solute and solvent flows within the membrane phase, and considerably in excess of the prediction for a diffusion process alone.     

Analysis of flow and vascular resistance in a model of the circle of Willis

A very simple model of the flow in the circle of Willis is described in this paper. Disregarding pulsatility and vessel wall elasticity, fluxes in all segments of the circle of Willis and its afferent and efferent vessels are calculated by applying the Poiseuille-Hagen formula. Comparison with the fluxes calculated numerically from a more sophisticated mathematical model, including pulsatility, vessel wall elasticity and nonlinear effects, revealed only very slight differences. In short, fluxes in the afferent vessels and the segments of the circle of Willis are influenced by any change of resistance within the network, whereas the fluxes in the efferent segments are dominated by the efferent resistance distribution. However, a great advantage of the present simple model is that it offers the possibility of an analytical approach which yields both an easy sensitivity analysis of parameters and an insight into the mechanisms that govern the flow in a network like the circle of Willis. It can be concluded that these mechanisms are similar to the principles of the Wheatstone bridge, known from electrical circuit theory.     

MuSICA, a CO2, water and energy multilayer, multileaf pine forest model: evaluation from hourly to yearly time scales and sensitivity analysis

The current emphasis on global climate studies has led the scientific community to set up a number of sites for measuring long‐term biospheric fluxes, and to develop a wide range of biosphere–atmosphere exchange models. This paper presents a new model of this type, which has been developed for a pine forest canopy. In most coniferous species the canopy layer is well separated from the understorey and several cohorts of needles coexist. It was therefore found necessary to distinguish several vegetation layers and, in each layer, several leaf classes defined not only by their light regime and wetness status but also by their age. This model, named MuSICA, is a multilayer, multileaf process‐based model. Each submodel is first independently parameterized using data collected at a EUROFLUX site near Bordeaux (Southwestern France). Particular care is brought to identify the seasonal variations in the various physiological parameters. The full model is then evaluated using a two‐year long data set, split up into 12 day‐type classes defined by the season, the weather type and the soil water status. Beyond the good overall agreement obtained between measured and modelled values at various time scales, several points of further improvement are identified. They concern the seasonal variations in the stomatal response of needles and the soil/litter respiration, as well as their interaction with soil or litter moisture. A sensitivity analysis to some of the model features (in‐canopy turbulent transfer scheme, leaf age classes, water retention, distinction between shaded and sunlit leaves, number of layers) is finally performed in order to evaluate whether significant simplifications can be brought to such a model with little loss in its predictive quality. The distinction between several leaf classes is crucial if one is to compute biospheric fluxes accurately. It is also evidenced that accounting for in‐canopy turbulent transfer leads to better estimates of the sensible heat flux.     

地表水热通量研究进展

介绍了当前国内外地表水热通景观测研究的进展及3种不同类型的土壤-植被-大气传输模型（SVAT）：单层模型、双层模型和多层模型。遥感手段常用于监测大面积地表水热通量。基于地表能量平衡方程,现已建立了许多遥感模型以估算水热通量（如简化模型、单层模型、附加阻抗模型、作物缺水指数模型和二源阻抗模型等）,并对这些模型复杂程度及应用范围进行了分析。     

A new method to model change in cutaneous blood flow due to mechanical skin irritation part II: parameter identification procedure

Mechanical skin irritation, for example a light scratch with a needle, induces histamine and neuropeptide release on the line of stroke and in the surrounding tissue. Both histamine and neuropeptides are vasodilators. They cause vasodilation by changing the contraction state of the vascular smooth muscles and hence vessel compliance. Smooth muscle contraction state is very difficult to measure in vivo. For that reason we propose in this article an identification procedure to establish an irritation law. The law gives change in vessel compliance as a function of space, time and the intensity of the stroke. We have showed that vessel compliance increases immediately after the stroke not only on the line of stroke, but also in the surrounding tissue. Then, after a short delay, vessel compliance starts decreasing in the surrounding tissue, whereas vessel compliance on the line of stroke keeps increasing. Hence, blood is transported from the surrounding tissue to the line of stroke. In this way, higher blood volume on the line of stroke can be obtained than by only changing vessel compliance locally.     

Effect of tidal volume and PEEP in ethchlorvynol-induced asymmetric lung injury.

We examined the effects of positive end-expiratory pressure (PEEP) and tidal volume on the distribution of ventilation and perfusion in a canine model of asymmetric lung injury. Unilateral right lung edema was established in 10 animals by use of a selective infusion of ethchlorvynol. Five animals were tested in the supine position (horizontal asymmetry) and five in the right decubitus position (vertical asymmetry). Raising PEEP from 5 to 12 cmH2O improved oxygenation despite a redistribution of blood flow toward the damage lung and a consistent decrease in total respiratory system compliance. This improvement paralleled a redistribution of tidal ventilation to the injured lung. This was effected primarily by a fall in the compliance of the noninjured lung due to hyperinflation. The effects of higher tidal volume were additive to those of PEEP. We propose that the major effect of PEEP in inhomogeneous lung injury is to restore tidal ventilation to a population of alveoli recruitable only at high airway pressures.     

The effects of diel changes in circulation and mixing on the longitudinal distribution of phytoplankton in a canyon‐shaped Mediterranean reservoir

1. The near‐surface distribution of phytoplankton cells along the thalweg of a canyon‐shaped reservoir (El Gergal, southern Spain) during two surveys is described and interpreted as the result of time‐varying large‐scale circulation patterns, vertical mixing processes and the physiological capacity of algal cells to regulate its position in the water column. 2. Vertical gradients of chlorophyll‐a concentration developed in the water column during the day but disappeared at night, as a result of the shoaling and deepening of the diurnal mixed layer (dml). The changes in the depth of the dml are largely controlled in El Gergal by convectively driven mixing processes. The longitudinal circulation changes, in turn, as a result of weak and diurnal land‐sea breezes. The distribution of algal cells was patchy at all times but did not change during any of the surveys. 3. An expression is proposed to estimate time scales for the development of horizontal patchiness T_P based on simple concepts of transport. It is shown that T_P is in the order of a week, indicating that horizontal patchiness does not respond immediately to hourly changes in the controlling factors. The magnitude of T_P, though, depends on how the vertical distribution of chlorophyll‐a and longitudinal currents change on subdiurnal time scales. In particular, T_P is sensitive to the lag existing between the momentum and heat fluxes through the free surface, driving circulation and vertical mixing.     

低覆盖度下两种行带式固沙林内风速流场和防风效果

研究在风速为10m/s和15m/s的风洞实验条件下,覆盖度为20%和25%的单行一带和两行一带模式乔木固沙林内的水平和垂直空间的风速变化情况,达到对两种不同模式的风速流场和防风效果进行比较分析的目的。通过分析得出:两种配置模式都形成了风影区和风速加速区相互组合的复杂的水平流场结构。两种模式对垂直空间风速影响相近,根据对不同高度风速的不同影响划分为微变化层(20-35 cm)、显著变化层(6-12 cm)和稳定变化层(0.4-3 cm)层次,两种模式在这几个层次风速表现出相同的变化规律。两行一带模式在第一带前降低水平空间风速的效果低于单行一带模式,第一带后高于后者。降低垂直空间风速规律为:对0.4-50 cm高度的风速均有一定的降低作用,0.4-12 cm高度的风速的降低效果较显著,且两行一带模式降低近地表(0.4 cm)风速的效果要高于单行一带模式。     

Modified heart-lung preparation for the evaluation of systolic and diastolic coronary flow in rats

A modified heart-lung preparation of the rat, which permits measuring systolic and diastolic coronary flow separately and enables coronary compliance to be evaluated, is described. The systemic circulation was substituted by a shunt circuit, and the elastic properties of the arterial tree were mimicked by a rubber balloon. Systolic and diastolic coronary flow was evaluated from the pulmonary and aortic flow signal. Integrated phasic pulmonary flow represented right ventricular stroke volume. Integrated phasic systolic aortic flow represented left ventricular stroke volume minus that volume flowing into the coronary arteries during systole, because the aortic flow probe had to be inserted distal to the origin of the coronary vessels. Because right and left ventricular stroke volume was identical under steady-state conditions, the difference between systolic pulmonary and systolic aortic flow resulted in systolic coronary flow. Diastolic coronary flow was measured by means of the retrograde flow through the aortic flow probe. Coronary compliance was calculated according to Frank's windkessel model from coronary resistance and from central diastolic aortic pressure, which decayed exponentially after switching out the rubber balloon and the shunt circuit. It could be shown that the proportion of systolic to diastolic coronary flow depends on coronary compliance.     

Numerical study on flows of red blood cells with liposome-encapsulated hemoglobin at microvascular bifurcation

Flow analysis at microvascular bifurcation after partial replacement of red blood cell (RBC) with liposome-encapsulated hemoglobin (LEH) was performed using the lattice Boltzmann method. A two-dimensional symmetric Y bifurcation model with a parent vessel diameter of 20 mum and daughter branch diameters of 20 microm was considered, and the distributions of the RBC, LEH, and oxygen fluxes were calculated. When only RBCs flow into the daughter branches with unevenly distributed flows, plasma separation occurred and the RBC flow to the lower-flow branch was disproportionately decreased. On the other hand, when half of RBC are replaced by LEH, the biasing of RBC flow was enhanced whereas LEH flowed favorably into the lower-flow branch, because many LEH within the parent vessel are suspended in the plasma layer, where no RBCs exist. Consequently, the branched oxygen fluxes became nearly proportional to flows. These results indicate that LEH facilitates oxygen supply to branches that are inaccessible to RBCs.     

Flow-tissue interaction with compliance mismatch in a model stented artery

The insertion of an endovascular prosthesis is known to have a thrombogenic effect that is also a consequence of the interaction between the flowing blood and the stented arterial segment; in fact the prosthesis induces a compliance mismatch and a possible small expansion along the vessel that eventually gives rise to an anomalous distribution of wall shear stresses. The fluid dynamics inside a rectilinear elastic vessel with compliance and section variation is studied here numerically. A recently introduced perturbative approach is employed to model the interaction between the fluid and the elastic tissue; this approximate technique is first validated by comparison with a complete solution within a simple one-dimensional model of the same system. Then it is applied to an axisymmetric model in order to evaluate the flow dynamics and the distribution of wall shear stress in the stented vessel. Compliance mismatch is shown to produce more intense negative wall shear stresses in the stented segment while rapid variations of wall shear stress are found at the stent ends. These effects are enhanced when the prosthesis is accompanied by a small increase of the vessel lumen.