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At least 253 records · Page 14Linked to original sources
PubMed2002

Diffusive permeability of rabbit peritoneum for small solutes in vitro: effect of gentamicin and insulin.

The purpose of the in vitro study was to compare the diffusive transport of creatinine, uric acid and glucose, directed from the interstitial (I) to the mesothelial (M) side of the peritoneum and in the opposite direction, before (15-60min) and after (75-120min) application of gentamicin and insulin. The experiments were undertaken on the rabbit parietal peritoneum in a modified Ussing chamber. A mathematical model was used to calculate a diffusive permeability coefficient P (in cm/s) and a diffusive mass transport coefficient KH (in mL/min). In the basic experimental series without drugs, the dynamics of peritoneal transport for examined solutes remained constant and there were no differences between transport directions (I--> M and M--> I). Mean values of P+/-SEM (KH+/-SEM) were 3.06+/-0.32 (321.1+/-33.5), 2.09+/-0.29 (219.2+/-30.7) and 2.73+/-0.47 (286.7+/-49.6) for creatinine, uric acid and glucose, respectively. The introduction of gentamicin decreased glucose transport directed from the mesothelial to the interstitial side of the membrane by about 12%. After insulin application we observed the increase of creatinine and glucose peritoneal transport rate. For creatinine, the above augmentation was by about 31% for I--> M and 83% for M--> I direction. In these conditions, the glucose transport directed from the interstitial to the mesothelial side of membrane increased by about 24%. Generally, in vitro gentamicin decreases, but insulin increases the diffusive permeability of the peritoneum for some small solutes. We suppose that these findings may be important for the efficiency of peritoneal dialysis.

Animals↗
PubMed1996

Measurement of liver blood flow using oxygen-15 labelled water and dynamic positron emission tomography: limitations of model description.

To date no satisfactory method has been available for the quantitative in vivo measurement of the complex hepatic blood flow. In this study two modelling approaches are proposed for the analysis of liver blood flow using positron emission tomography (PET). Five experiments were performed on three foxhounds. The anaesthetised dogs were each given an intravenous bolus injection of oxygen-15 labelled water, and their livers were then scanned using PET. Radioactivity in the blood from the aorta and portal vein was measured directly and simultaneously using closed external circuits. Time-activity curves were constructed from sequential PET data. Data analysis was performed by assuming that water behaves as a freely diffusible tracer and adapting the standard one-compartment blood flow model to describe the dual blood supply of the liver. Two particular modelling approaches were investigated: the dual-input model used both directly measured input functions (i.e. using the hepatic artery and the portal vein input, determined from the radioactivity detected in the aorta and portal vein respectively) whereas the single-input model used only the measured arterial curve and predicted the corresponding portal input function. Hepatic arterial flow, portal flow and blood volume were fitted from the PET data in several regions of the liver. The resulting estimates were then compared with reference blood flow measurements, obtained using a standard microsphere technique. The microspheres were injected in a separate experiment on the same dogs immediately prior to PET scanning. Whilst neither the single- nor the dual-input models accurately reproduced the arterial reference flow values, the flow values from the single-input model were closer to the microsphere flow values. The proposed single-input model would be a good approximation for liver blood flow measurements in man. The observed discrepancies between the PET and microsphere flow values may be due to the inherent temporal and spatial heterogeneity of liver blood flow. The results presented suggest that adaptation of the standard one-compartment blood flow model to describe the dual blood supply of the liver is limited and other flow tracers have to be considered for quantitative PET measurements in the liver.

Animals↗
PubMed2000

Caco-2 versus Caco-2/HT29-MTX co-cultured cell lines: permeabilities via diffusion, inside- and outside-directed carrier-mediated transport.

PURPOSE: The objective of this study was a systematic characterization and evaluation of cell culture models based on mixtures of Caco-2/HT29-MTX co-cultures for their use in screening for drug absorption and intestinal permeability in comparison to the properties of the respective mono-cultures. METHODS: Co-cultures of Caco-2 cells (absorptive-type) and HT29-MTX cells (goblet-type) were set up. Three different co-cultures (initial seeding ratios Caco-2/HT29-MTX: 90/10, 70/30, and 50/50) were grown on permeable filter supports, and monolayers were used for permeability studies with model compounds for paracellular absorption (atenolol, furosemide, H334/75, mannitol, terbutaline), transcellular absorption (antipyrine, ketoprofen, metoprolol, piroxicam), carrier-mediated absorption (D-glucose, Gly-Pro, and L-phenylalanine) as well as substrates for carrier-mediated secretion via P-glycoprotein (cimetidine and talinolol). Electrophysiological and microscopic controls were performed to characterize the cell cultures. RESULTS: For compounds undergoing passive intestinal absorption permeabilities were generally higher in co-cultures than in Caco-2 monolayers, yielding highest values in pure HT29-MTX monolayers. This difference was most obvious for compounds transported via the paracellular pathway, where HT29-MTX cells may be up to 30 times more permeable than Caco-2 cells, whereas for lipophilic and highly permeable compounds, the difference in permeability values was less obvious. For drugs undergoing intestinal secretion mediated by P-glycoprotein, co-cultivation of Caco-2 cells with HT29-MTX cells led to increased apical to basolateral permeability which was decreased in the opposite direction, consistent with the fact that HT29-MTX cells do not express P-glycoprotein. When a carrier-mediated absorption mechanism is involved, the permeabilities observed were lower than the values reported for human small intestine and co-cultivation of HT29-MTX cells with Caco-2 cells resulted in even lower values as compared to the plain Caco-2 cultures. CONCLUSIONS: Co-cultures of HT29-MTX and Caco-2 cells offer the opportunity of modifying the permeability barrier of the cell monolayers both with respect to paracellular resistance and secretory transport via P-gp. Thus, in special cases, they allow more flexibility in adapting the in vitro system to the in vivo situation as compared to the monocultures. Another advantage is the obvious robustness of the method with respect to the reproducibility of the results. A problem remaining, however, is the quantitative expression of carriers involved in intestinal uptake of many nutrients and drugs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

Direct calculation of light-induced structural change and diffusive motion in glassy As2Se3

Photostructural change of glassy As2Se3 was simulated on an experimentally credible model with excited electronic dynamics within first-principles molecular dynamics. Bond breaking and bond switching reactions account for local changes around defect sites at the short time phase of illumination. For long-time relaxation, defect pairs associated with band tail states become involved in a rearrangement in the network, giving rise to a low energy, nonlocal "polaronlike" collective oscillation. Diffusive motion is observed for short times, which we tentatively interpret as the initial phase of athermal photomelting.

Journal Article↗
PubMed2005

Simulation of anisotropic growth of low-grade gliomas using diffusion tensor imaging.

A recent computational model of brain tumor growth, developed to better describe how gliomas invade through the adjacent brain parenchyma, is based on two major elements: cell proliferation and isotropic cell diffusion. On the basis of this model, glioma growth has been simulated in a virtual brain, provided by a 3D segmented MRI atlas. However, it is commonly accepted that glial cells preferentially migrate along the direction of fiber tracts. Therefore, in this paper, the model has been improved by including anisotropic extension of gliomas. The method is based on a cell diffusion tensor derived from water diffusion tensor (as given by MRI diffusion tensor imaging). Results of simulations have been compared with two clinical examples demonstrating typical growth patterns of low-grade gliomas centered around the insula. The shape and the kinetic evolution are better simulated with anisotropic rather than isotropic diffusion. The best fit is obtained when the anisotropy of the cell diffusion tensor is increased to greater anisotropy than the observed water diffusion tensor. The shape of the tumor is also influenced by the initial location of the tumor. Anisotropic brain tumor growth simulations provide a means to determine the initial location of a low-grade glioma as well as its cell diffusion tensor, both of which might reflect the biological characteristics of invasion.

Anisotropy↗
PubMed2004

Restricted diffusion and release of aroma molecules from sol-gel-made porous silica particles.

The aim of the current study is to predict the release kinetics of organic molecules entrapped in sol-gel-made silica particles using both pulsed field gradient-nuclear magnetic resonance (PFG-NMR) techniques and model calculations to describe restricted diffusion. The macroscopic release profile of aroma molecules from sol-gel-made particles is measured directly by UV-VIS spectroscopy, while the release kinetics are calculated by the Crank equation. The microscopic restricted pore diffusion coefficient of the aroma molecules in the Crank equation is obtained in situ by pulsed field gradient (PFG) magic angle spinning (MAS) nuclear magnetic resonance (NMR). Furthermore, restricted pore diffusion coefficients obtained by model calculations are in agreement with those measured by PFG-MAS-NMR, indicating the potential of the latter for characterization and screening of encapsulation formulations. Measured and calculated release profiles agree within experimental error.

Diffusion↗
PubMed2000

A generalized transport model for biased cell migration in an anisotropic environment.

A generalized transport model is derived for cell migration in an anisotropic environment and is applied to the specific cases of biased cell migration in a gradient of a stimulus (taxis; e.g., chemotaxis or haptotaxis) or along an axis of anisotropy (e.g., contact guidance). The model accounts for spatial or directional dependence of cell speed and cell turning behavior to predict a constitutive cell flux equation with drift velocity and diffusivity tensor (termed random motility tensor) that are explicit functions of the parameters of the underlying random walk model. This model provides the connection between cell locomotion and the resulting persistent random walk behavior to the observed cell migration on longer time scales, thus it provides a framework for interpreting cell migration data in terms of underlying motility mechanisms.

Anisotropy↗
PubMed2005

Flow-based fiber tracking with diffusion tensor and q-ball data: validation and comparison to principal diffusion direction techniques.

In this study, we evaluate the performance of a flow-based surface evolution fiber tracking algorithm by means of a physical anisotropic diffusion phantom with known connectivity. We introduce a novel speed function for surface evolution that is derived from either diffusion tensor (DT) data, high angular resolution diffusion (HARD) data, or a combined DT-HARD hybrid approach. We use the model-free q-ball imaging (QBI) approach for HARD reconstruction. The anisotropic diffusion phantom allows us to compare and evaluate the performance of different fiber tracking approaches in the presence of real imaging artifacts, noise, and subvoxel partial volume averaging of fiber directions. The surface evolution approach, using the full diffusion tensor as opposed to the principal diffusion direction (PDD) only, is compared to PDD-based line propagation fiber tracking. Additionally, DT reconstruction is compared to HARD reconstruction for fiber tracking, both using surface evolution. We show the potential for surface evolution using the full diffusion tensor to map connections in regions of subvoxel partial volume averaging of fiber directions, which can be difficult to map with PDD-based methods. We then show that the fiber tracking results can be improved by using high angular resolution reconstruction of the diffusion orientation distribution function in cases where the diffusion tensor model fits the data poorly.

Algorithms↗
PubMed2005

Axial asymmetry of water diffusion in brain white matter.

The diffusion tensor (DT) is a three-dimensional (3D) model of diffusivity in biological tissues. In white matter (WM), the major eigenvector, which is the direction of greatest diffusivity, is generally assumed to align with the direction of the fiber bundles. The distribution of major eigenvectors in WM has been investigated using color-based maps and WM tractography (WMT). However, anatomical patterns in the medium and minor eigenvector directions have largely been ignored in DTI studies of the human brain. In this study, the patterns of medium and minor eigenvectors in the brain were investigated using both color-based maps and WMT. Specific WM structures, such as the corona radiata, internal and external capsules, sagittal stratum, cingulum, and superior longitudinal fasciculus, demonstrated coherent patterns in the medium and minor eigenvector directions. These patterns were consistent across subjects. The orthogonal or axial diffusion asymmetry may be explained by merging, diverging, or crossing fiber geometries. The effects of orthogonal diffusion asymmetry on WMT were also investigated. This study shows that WM axial asymmetry causes anisotropic dispersion patterns in the estimated tract trajectories. The medium and minor eigenvector patterns may be useful for elucidating the local dispersion distributions of WM tracts.

Adolescent↗
PubMed2003

A geometric theory of chaotic phase synchronization.

A rigorous mathematical treatment of chaotic phase synchronization is still lacking, although it has been observed in many numerical and experimental studies. In this article we address the extension of results on phase synchronization in periodic oscillators to systems with phase coherent chaotic attractors with small phase diffusion. As models of such systems we consider special flows over diffeomorphisms in which the neutral direction is periodically perturbed. A generalization of the Averaging Theorem for periodic systems is used to extend Kuramoto's geometric theory of phase locking in periodically forced limit cycle oscillators to this class of systems. This approach results in reduced equations describing the dynamics of the phase difference between drive and response systems over long time intervals. The reduced equations are used to illustrate how the structure of a chaotic attractor is important in its response to a periodic perturbation, and to conclude that chaotic phase coherent systems may not always be treated as noisy periodic oscillators in this context. Although this approach is strictly justified for periodic perturbations affecting only the phase variable of a chaotic oscillator, we argue that these ideas are applicable much more generally.

Models, Theoretical↗
PubMed2001

Single molecule tracking of heterogeneous diffusion.

The mean square displacement of heterogeneous diffusion obeys the Einstein relation, thereby showing no sign of heterogeneities in the ensemble measurement of the diffusion constant. The signature of spatial heterogeneities appears in the time evolution of the non-Gaussian distribution and in the cross correlation between the square displacements at different times, both available from single molecule diffusional trajectories. As a quantitative measure, the non-Gaussian indicator g(t) decays asymptotically to zero according to 1/t for finite time correlation, but saturates at a plateau value for power-law correlation. In addition, the joint moment correlation function f(t,tau) provides a direct probe of the memory effect of the fluctuating rate constant. A two-state diffusion model and a stochastic Gaussian model are constructed to evaluate these quantities and are shown to yield the same result within the second cumulant expansion.

Journal Article↗
PubMed2002

Directed random walks in continuous space.

The investigation on diffusion with directed motion in a two-dimensional continuous space is completed by using the model of the continuous directed random walks. The average square end-to-end distance approximately t(2nu) is calculated. The results show that this type of walks belongs asymptotically to the same class (nu=1.0) as the ballistic motions. For short time, we observe a crossover from purely random walks (nu=0.5) to ballistic motions (nu=1.0). The dependence of the crossover on the direction parameter theta is studied. There exists a scaling relation of the form approximately tf(t/theta(-2)). The return probability P00(t) is also investigated and the scaling form similar to is obtained.

Journal Article↗
PubMed2000

Resistance resonance effects through magnetic edge states.

We report on the magnetoresistance of a two-dimensional electron gas subjected to an abrupt magnetic field gradient arising from a ferromagnetic stripe fabricated at its surface. A sharp resistance resonance effect is observed at B(p) due to the formation of two types of magnetic edge states that drift in opposite directions perpendicular to the magnetic field gradient for B B(p). A semiclassical drift-diffusion model gives a good description of the effects of the magnetic confinement on both the diagonal and off-diagonal components of the resistivity tensor.

Journal Article↗
PubMedDate not supplied

Temperature mapping of laser-induced hyperthermia in an ocular phantom using magnetic resonance thermography.

Laser-induced heating in an ocular phantom is measured with magnetic resonance thermography (MRT) using temperature-dependent phase changes in proton resonance frequency. The ocular phantom contains a layer of melanosomes isolated from bovine retinal pigment epithelium. The phantom is heated by the 806-nm output of a continuous wave diode laser with an irradiance of 2.4 to 21.6 W/cm2 in a beam radius of 0.8 or 2.4 mm, depending on the experiment. MRT is performed with a 2 T magnet, and a two-turn, 6-cm-diam, circular radio frequency coil. Two-dimensional temperature gradients are measured within the plane of the melanin layer, as well as normal to it, with a temperature resolution of 1 degrees C or better. The temperature gradients extending within the melanin layer are broader than those orthogonal to the layer, consistent with the higher optical absorption and consequent heating in the melanin. The temperature gradients in the phantom measured by MRT closely approximate the predictions of a classical heat diffusion model. Three-dimensional temperature maps with a spatial resolution of 0.25 mm in all directions are also made. Although the temporal resolution is limited in the prototype system (22.9 s for a single image "slice"), improvements in future implementations are likely. These results indicate that MRT has sufficient spatial and temperature resolution to monitor target tissue temperature during transpupillary thermotherapy in the human eye.

Animals↗
PubMed1994

Direct observation of tube-like motion of a single polymer chain.

Tube-like motion of a single, fluorescently labeled molecule of DNA in an entangled solution of unlabeled lambda-phage DNA molecules was observed by fluorescence microscopy. One end of a 16- to 100-micrometer-long DNA was attached to a 1-micrometer bead and moved with optical tweezers. The molecule was stretched into various conformations having bends, kinks, and loops. As the polymer relaxed, it closely followed a path defined by its initial contour. The relaxation time of the disturbance caused by the bead was roughly 1 second, whereas tube-like motion in small loops persisted for longer than 2 minutes. Tube deformation, constraint release, and excess chain segment diffusion were also observed. These observations provide direct evidence for several key assumptions in the reptation model developed by de Gennes, Edwards, and Doi.

Bacteriophage lambda↗
PubMedDate not supplied

[Asymptotic solution of the model of the erythrocyte shape as an autowave process].

An asymptotic solution was plotted for a model of erythrocyte forms assuming that the biomembrane is anisotropic and of "small" thickness. This leads to small non-linearity and low diffusion, therefore the solution is unrelaxational. The model was investigated qualitatively assuming that the liquid current directed inside the spheric membrane induces its "distension", while that directed outside-its "crumpling". In the spherical system of coordinates the lines of solution level at theta = const are circumferences, while at phi-const-trochoids (Pascal coil, for example). Trochoids rotation areas show stomacyte and discocyte forms. Several hypotheses based on the analysis performed are advanced.

Erythrocyte Membrane↗
PubMed1991

Stromal regulation of epithelial function.

Stromal influences upon epithelia are part of a continuum of cellular interactions that begins at fertilization and extends into adulthood. In parenchymal organs, the most thoroughly characterized interactions have been those that occur during development between mesenchyme, embryonic stroma, and epithelium. Mesenchyme is essential for epithelial proliferation, morphogenesis, and differentiation. Hormones affect stromal-epithelial interactions, and in some cases, steroid hormones may produce their effects on the epithelium indirectly, acting via the mesenchyme. In many adult organs the epithelia continually proliferate and differentiate and consequently may be considered developing systems within the mature organism. This is especially true in organs with a rapidly renewing epithelium, such as the intestine, and in organs that have cycles of functional activity, such as those of the female reproductive system. The mechanisms by which stroma affects epithelial structure and function are not well understood. Current models of how signaling may be accomplished include transmission via diffusible substances, via the extracellular matrix (ECM), and via direct cell-cell contact. Growth factors and organ-specific paracrine factors are candidates for stromal cues that affect the epithelium in some systems. Components of the ECM appear to play a role in permissive interactions and may affect epithelial function by changing cell shape or by binding ECM to the cell surface integrin receptors. Signaling via direct stromal-epithelial contact may be accomplished via interactions between complimentary cell surface adhesion molecules. The importance of stromal-epithelial interactions is reemphasized by several models of carcinogenesis that suggest that perturbations in these interactions may be involved in tumor progression.

Adult↗
PubMed2005

Novel delivery of oligonucleotides using a topical hydrogel tissue sealant in a murine partial nephrectomy model.

PURPOSE: Ischemia/reperfusion injury is a leading cause of renal damage and antisense gene therapy has been shown to ameliorate its effects. However, this approach has been limited by current delivery methods that require high concentrations of intravenous nucleic acids lacking specificity for targeting tissues. To overcome these limitations we developed a novel murine partial nephrectomy model to evaluate polyethylene-glycol (PEG) hydrogel tissue sealant as a topical oligonucleotide delivery system. MATERIALS AND METHODS: A total of 18 male C57BL/6 mice underwent left partial nephrectomy with vascular occlusion. Hydrogel primer and then sealant were applied to the cut surface and photopolymerized. Using this method 16 additional mice received hydrogel primer mixed with Cy5 labeled fluorescent oligonucleotide (10 to 100 microg). Kidneys were harvested at various time points and assessed for oligonucleotide penetration using fluorescence microscopy. RESULTS: A survival rate of 100% (34 subjects) was obtained using this mouse model of partial nephrectomy. PEG hydrogel provided adequate protection against renal hematoma and intraperitoneal blood. Fluorescent images revealed that 50 microg was the minimum dose resulting in complete progressive cellular penetration with time. In addition to direct diffusion from the application site, movement of oligonucleotide through the subcapsular space into the cortex was an observed mechanism of distribution. CONCLUSIONS: A murine partial nephrectomy model was successfully created using PEG hydrogel. In addition to achieving hemostasis, hydrogel served as a successful depot for delivering oligonucleotides throughout the kidney.

Animals↗