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At least 631 records · Page 35Linked to original sources
PubMed2002

Neuroimmunophilin ligand V-10,367 is neuroprotective after 24-hour delayed administration in a mouse model of diffuse traumatic brain injury.

The authors present two studies that investigate the biochemical and histologic effects of the nonimmunosuppressive neuroimmunophilin (NIMM) ligand V-10,367 in a mouse model of traumatic brain injury (TBI). In study 1, the authors examined the effect of V-10,367 (50 mg/kg x 2 per day, by mouth) on neurofilament M (NFM) protein levels and on alpha-spectrin breakdown products (SBDPs) when dosed for 2 days, starting 24 hours after TBI and killed on day 3. In study 2, V-10,367 was given for 10 days, starting 24 hours after TBI and the mice killed 6 weeks after TBI, to measure the extent of neurodegeneration (amino CuAg stain). The results in study 1 revealed that V-10,367-treatment significantly increased NFM protein levels in both sham and TBI mice. In addition, V-10,367 attenuated SBDP 150 levels in the cortex, striatum, and hippocampus. The results of study 2 indicated that TBI mice treated with V-10,367 demonstrated significantly less neurodegeneration compared to injured, vehicle-treated mice. In summary, these results suggest that NIMMs may be neuroprotective indirectly through inhibition of calpain-mediated cytoskeletal damage and perhaps via maintenance of neuronal plasticity. In the context of this mouse model of TBI, the therapeutic window for V-10,367's positive effects is at least 24 hours after injury, which, in the case of TBI models, is largely unprecedented for a neuroprotective compound.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1992

Neurotransmitter release: facilitation and three-dimensional diffusion of intracellular calcium.

In order to account for the time courses of both evoked release and facilitation, in the framework of the Ca2+ hypothesis, Fogelson and Zucker (1985, Biophys. J. 48, 1003-1017) suggested treating diffusion of Ca2+, once it enters through the Ca2+ channels, as a three-dimensional process (three-dimensional diffusion model). This model is examined here as a refined version of the "Ca(2+)-theory" for neurotransmitter release. The three-dimensional model was suggested to account for both the time course of release and that of facilitation. As such, it has been examined here as to its ability to predict the dependence of the amplitude and time course of facilitation under various experimental conditions. It is demonstrated that the three-dimensional diffusion model predicts the time course of facilitation to be insensitive to temperature. It also predicts the amplitude and time course of facilitation to be independent of extracellular Ca2+ concentration. Moreover, it predicts that inhibition of the [Na+]o in equilibrium with [Ca2+]i exchange does not alter facilitation. These predictions are not upheld by the experimental results. Facilitation is prolonged upon reduction in temperature. The amplitude of facilitation declines and its duration is prolonged upon increase in extracellular Ca2+ concentration. Finally, inhibition of the [Na+]o in equilibrium with [Ca2+]i exchange prolongs facilitation but does not alter the time course of evoked release after an impulse.

Animals↗
PubMed1990

Modeling the Drosophila pair-rule pattern by reaction-diffusion: gap input and pattern control in a 4-morphogen system.

Various reaction-diffusion models will produce striped patterns, but the most effective models so far devised to do this require two matched pairs of interacting morphogens, i.e. four substances in all. This paper examines the behavior of one such model, of a fairly generalized type, and its application to the process of pair-rule pattern formation during Drosophila embryogenesis. It is assumed that the two self-activating morphogens required by the model, expressed in complementary out-of-phase stripes, are products of early-acting pair-rule genes. Possible candidates include the primary pair-rule genes, hairy and runt. The conditions under which regular stripes are generated by the model are then examined, with emphasis on the way pre-existing patterns act to control stripe formation via their effect on rates of reaction within the pair-rule system, specifically rates of pair-rule gene transcription, to show how gap gene products may act during pattern formation. A fully symmetrical set of reactions, in which rates of formation, self- and cross-activation are exactly matched, gives unaligned stripes. Pronounced asymmetries in this regard, e.g. differential rates of formation or self-activation, destabilize stripes or produce local interruptions in the pattern like those seen in gap mutants. A limited degree of asymmetry, coupled with a gradient in the value of one or more parameters will give a correctly aligned, well-controlled pattern of stripes. The experimental evidence indicates that gap genes could be responsible for both of these effects: they activate the pair-rule system asymmetrically and, when first expressed, generate a sufficiently complex landscape of concentration peaks and gradations to provide the local cues needed to correctly position and align the pair-rule stripes. In this respect, the pair-rule system can be viewed as having an intrinsic pattern-forming capability, but it depends on the input of gap genes for pattern control. Gradients are involved, but from this analysis, it is the graded distribution of gap products that is important, not the overall antero-posterior gradient. The uniform spacing of stripes, despite underlying peaks and troughs of gap gene expression, shows that pattern wavelength is relatively insensitive to parameter change, also a property of the model.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2002

Lateral diffusion in substrate-supported lipid monolayers as a function of ambient relative humidity.

We analyzed the influence of water activity on the lateral self-diffusion of supported phospholipid monolayers. Lipid monolayer membranes were supported by polysaccharide cushions (chitosan and agarose), or glass. A simple diffusion model was derived, based on activated diffusion with an activation energy, E(a), which depends on the hydration state of the lipid headgroup. A crucial assumption of the derived model is that E(a) can be calculated assuming an exponential decay of the humidity-dependent disjoining pressure in the monolayer/substrate interface with respect to the equilibrium separation distance. A plot of ln(D) against ln(p(0)/p), where D is the measured diffusion coefficient and p(0) and p are the partial water pressures at saturation and at a particular relative humidity, respectively, was observed to be linear in all cases (i.e., for differing lipids, lateral monolayer pressures, temperatures, and substrates), in accordance with the above-mentioned diffusion model. No indications for humidity-induced first-order phase transitions in the supported phospholipid monolayers were found. Many biological processes such as vesicle fusion and recognition processes involve dehydration/hydration cycles, and it can be expected that the water activity significantly affects the kinetics of these processes in a manner similar to that examined in the present work.

Biophysical Phenomena↗
PubMed1992

[The modelling of diffuse peritonitis].

Peritonitis is still an urgent problem and its solution is determined to a great measure by purposeful studies in the field of pathogenesis and treatment. The creation of adequate models of peritonitis acquires particular significance. Eighty-four animals (dogs) were used to create the model. It is shown in the work that a standard model of generalized peritonitis can be produced by two injections of a polymicrobial suspension consisting of the most commonly encountered peritoneal microbes E. coli and B. fragilis. The suspension is injected into different levels of the abdominal cavity. With this method of administration of the polymicrobial suspension the model was reproduced in 90% of cases. Thus, the developed model resembles human peritonitis in the clinical picture and the laboratory and morphological values.

Animals↗
PubMed2001

Spatial and temporal variance of river discharge on Okinawa (Japan): inferring the temporal impact on adjacent coral reefs.

Land-use changes and associated river discharges in coastal tropical regions present a global threat to coral reef environments. This study investigated the temporal variation in biological oxygen demand (BOD5) and suspended particulate matter (SPM) at the mouths of seven rivers on Okinawa Island (Japan) over 20 years. We report strong positive relationships between human population densities within river catchment areas and both average BOD5 concentration (r2 = 0.968; p < 0.001) and SPM (r2 = 0.659; p < 0.003) at the mouths of the rivers. At the reef adjacent to one river (Hija River, 50.2 km2 catchment area) we applied moving window analysis to assess an optimal sampling strategy for elucidating transitional boundaries in coral composition from the river mouth to a point where the effect of river discharge was minimal. The optimal window width for Okinawan rivers was five 1 m2 quadrats spaced over 5 m intervals. This sampling strategy clearly showed dissimilarity spikes in coral community composition up to 400 m from the Hija River mouth, beyond which no significant differences in coral composition were detected using analysis of similarities (ANOSIM). We developed a simple diffusion model linking the rivers' maximum discharge rate, and the average concentration of BOD5 and SPM with the spatial impact on the coral communities. The diffusion model can aid in predicting negative shifts in coral communities expected to result from detrimental land-use changes and is an important tool for monitoring coral reefs.

Animals↗
PubMed2004

Diffusion of innovation theory for clinical change.

Maximising the adoption of evidence-based practice has been argued to be a major factor in determining healthcare outcomes. However, there are gaps between evidence-based recommendations and current care. Bridging the evidence gap will not be achieved simply by informing clinicians about the evidence. One theoretical approach to understanding how change may be achieved is Rogers' diffusion model. He argues that certain characteristics of the innovation itself may facilitate its adoption. Other factors influencing acceptance include promotion by influential role models, the degree of complexity of the change, compatibility with existing values and needs, and the ability to test and modify the new procedure before adopting it. The diffusion model may provide valuable insights into why some practices change and others do not, as well as guiding those who try to effect adoption of best-evidence practice.

Communication↗
PubMed2005

Quantitative measurements of NO reaction kinetics with a Clark-type electrode.

Nitric oxide (NO) plays important physiological roles in the body. Knowledge regarding the kinetics of NO catabolism is important for understanding the biological functions of NO. Clark-type NO electrodes have been frequently employed in measuring the kinetics of NO reactions; however, the slow response time of these electrodes can cause measurement errors and limit the application of the electrode in measurements of fast NO reactions. In this study, a simplified diffusion model is given for describing the response process of the NO electrode to the change of NO concentration. The least-square method is used in fitting the currents calculated from the diffusion equation to the experimental curves for determining the diffusion parameters and rate constants. The calculated currents are in excellent accordance with the experimental curves for different NO reaction kinetics. It has been demonstrated that when using an NO electrode with a response time of approximately 6 s to measure fast NO reactions with a half-life of approximately 1s, the response currents of the electrode have large differences compared to the curve of actual NO concentration in the solution; however, the rate constant of NO decay can still be accurately determined by computer simulations with the simplified diffusion model. Theoretical analysis shows that an NO electrode with a response time of 6 s (D/L2=0.06 s-1) and the lowest detection limit of 1 nM NO can be used in measuring kinetics of extremely rapid NO reactions with a half-life below 10 ms.

Animals↗
PubMed1998

Effects of diaspirin cross-linked haemoglobin on post-traumatic cerebral perfusion pressure and blood flow in a rodent model of diffuse brain injury.

Diaspirin cross-linked haemoglobin (DCLHb) is a new oxygen carrying blood substitute with vasoactive properties. Vasoactive properties may be mediated via high affinity binding of nitric oxide by the haem moiety. Using a rodent model of head injury combined with ischaemia, we studied the effects of DCLHb on cerebral blood flow (CBF) and intracranial pressure (ICP). Twenty anaesthetized rats were allocated randomly to receive treatment with DCLHb 400 mg kg-1 i.v. or placebo (oncotically matched plasma protein substitute 4.5% i.v.). To produce diffusely increased ICP, after a severe weight drop injury, all animals underwent a 30-min period of bilateral carotid ligation combined with a period of induced hypotension. After reperfusion, DCLHb or placebo was infused and the animals instrumented for measurement of intraventricular ICP and CBF in the region of the sensorimotor cortex using the hydrogen clearance technique. Mean arterial pressure (MAP), ICP, cerebral perfusion pressure (CPP) (CPP = MAP - ICP) and CBF were measured 4 h after injury in all animals. DCLHb significantly reduced ICP from mean 13 (SEM 2) to 3 (1) mm Hg (P < 0.001), increased CPP from 52 (8) to 95 (6) mm Hg (P < 0.001) and increased CBF from 21 (2) to 29 (2) ml 100 g-1 min-1 (P = 0.032). We conclude that DCLHb improved CPP without a reduction in CBF in a rodent model of post-traumatic brain swelling.

Animals↗
PubMed1994

Aerosol transmission of a viable virus affecting swine: explanation of an epizootic of pseudorabies.

A Gaussian diffusion model was applied to an epizootic of pseudorabies in ten swine herds located in Decatur County, Indiana, USA to test the hypothesis that the virus can be spread via aerosol. The epizootic occurred during January to March, 1988, spreading through ten farms across an area of about 150 km2. The model included a receptor component that provided an estimate of viruses received by the pig within an enclosed barn. Results show that the diffusion model can explain the spread of the virus during the epizootic for all nine farms to which the virus spread.

Air Microbiology↗
PubMed2001

SPET of a computerised model of diffuse lung disease.

Emphysema is a common and debilitating disease that is the commonest cause of end-stage respiratory failure. Treatment is either by lung transplantation or by lung volume reduction surgery (LVRS) that improves the biomechanics of respiration. Patient selection for LVRS hinges on the demonstration of heterogeneous disease, predominantly involving the upper lobes, as a good surgical outcome is most likely in these patients. We used a virtual model of lung scintigraphy to compare planar with tomographic scintigraphy for the detection of diffuse lung disease. Lesions of the magnitude of the lung acinus, as well as larger and smaller lesions, were distributed throughout the lungs in volumes from 2% to 50%. Single-photon emission tomography does not add incremental value to planar images for the detection of diffuse lung disease.

Adult↗
PubMedDate not supplied

A framework based on spin glass models for the inference of anatomical connectivity from diffusion-weighted MR data - a technical review.

A family of methods aiming at the reconstruction of a putative fascicle map from any diffusion-weighted dataset is proposed. This fascicle map is defined as a trade-off between local information on voxel microstructure provided by diffusion data and a priori information on the low curvature of plausible fascicles. The optimal fascicle map is the minimum energy configuration of a simulated spin glass in which each spin represents a fascicle piece. This spin glass is embedded into a simulated magnetic external field that tends to align the spins along the more probable fiber orientations according to diffusion models. A model of spin interactions related to the curvature of the underlying fascicles introduces a low bending potential constraint. Hence, the optimal configuration is a trade-off between these two kind of forces acting on the spins. Experimental results are presented for the simplest spin glass model made up of compass needles located in the center of each voxel of a tensor based acquisition.

Algorithms↗
PubMed2002

Dose reconstruction in irradiated Fricke-agarose gels by means of MRI and optical techniques: 2D modelling of diffusion of ferric ions.

Fricke-agarose gels have elicited much interest in the field of radiation dosimetry, as tissue-equivalent dosemeters. magnetic resonance (MR) relaxation rates are measured for dose reconstruction. A major problem of Fricke-agarose gels is the diffusion of the ferric ions formed after irradiation. Knowledge of the diffusion coefficient of ferric ions may be necessary. Xylene orange, a dye that specifically chelates ferric ions, was added to the Fricke gel system to reduce ion diffusion and, as the binding gives a coloured complex, to allow optical detection of ferric ions. Diffusion of ferric ions in two dimensions and time evolution of ion concentration were evaluated. MR images were obtained at different times after irradiation. Ferric ion distribution, the corresponding images and the doses at different times after irradiation were reconstructed taking into account the calculated diffusion coefficients. Diffusion was then estimated by means of two different optical methods. The agreement obtained supports the reliability of the MRI method and of the model.

Gels↗
PubMed1981

Slow diffusion of Ca2+ in the rat's hippocampus.

Ca2+-sensitive microelectrodes, attached to CaCl2-containing micropipettes, were inserted into the dorsal hippocampus of rats under urethane. When Ca2+ was released iontophoretically, the amplitude and time course of the resultant increase in extracellular ca2+ concentration could be fitted to a simple diffusion model, but the apparent diffusion coefficient of Ca2+ was only about 1/100 of its value in water, possibly because of reversible Ca/+ binding to hippocampal tissue. A further anomaly was a very low transport number (less than 0.01) for the release of Ca2+ from microelectrodes in vivo.

Animals↗
PubMed1996

Physical effects of biologically formed cholesterol oxidation products on lipid membranes investigated with fluorescence depolarization spectroscopy and electron spin resonance.

Planar oriented membranes of 1-palmitoyl, 2-oleoyl-phosphatidylcholine (POPC) containing cholesterol, 19-hydroxycholesterol, 22S-hydroxycholesterol, or 25-hydroxycholesterol in concentrations up to 5 mol % were investigated with angle-resolved fluorescence depolarization and electron spin resonance measurements. Analyses of the data with the Brownian diffusion model show that the oxysterols have structural effects similar to those of cholesterol: an increase in molecular order and no change in the rotational diffusion coefficients of the probe molecules. Time-resolved fluorescence anisotropy measurements on diphenylhexatriene (DPH) in small unilamellar vesicles of POPC and DOPC were performed using oxysterols commonly found in oxidized low density lipoproteins (LDL) in comparison to membranes containing cholesterol or no sterols. Analyses using the Brownian rotational diffusion model show that most LDL-oxysterols affect the vesicle physical structure in a manner similar to cholesterol, viz. an increase in molecular order and a decrease in the dynamics. Cholesterol-alpha-epoxide has a much smaller ordering effect than cholesterol in POPC-vesicles. A similar effect was found for 7 beta-hydroxycholesterol in DOPC-vesicles. The tendency of the oxysterols to influence the molecular order as compared to pure cholesterol may contribute to cell membrane permeability changes affecting crucial cell functions and events leading to vascular cell injury. Increased LDL oxysterol levels may account for some of the structural changes noted for oxidatively modified LDL as well as its toxicity to vascular cells.

Cholesterol↗
PubMed2006

Substrate and metabolite diffusion within model medium for soft cheese in relation to growth of Penicillium camembertii.

Penicillium camembertii was cultivated on a jellified peptone-lactate based medium to simulate the composition of Camembert cheese. Diffusional limitations due to substrate consumption were not involved in the linear growth recorded during culture, while nitrogen (peptone) limitation accounted for growth cessation. Examination of gradients confirmed that medium neutralization was the consequence of lactate consumption and ammonium production. The diffusion of the lactate assimilated from the core to the rind and that of the ammonium produced from the rind to the core was described by means of a diffusion/reaction model involving a partial linking of consumption or production to growth. The model matched experimental data throughout growth.

Cheese↗
PubMed1995

A diffusion-reaction model of nerve regeneration.

The process of peripheral nerve regeneration has been modeled using 5 populations of mathematical variables to represent the biological activities of Wallerian degeneration, fibrin matrix development, Schwann cell activity, elongating neurites, and neovascularization. The mathematical model provided simulations of nerve regeneration following transection and crush injuries that correspond with growth behaviors quantified in biological experiments. Neovascularization was spatiotemporally quantified in nerve regeneration chambers and following nerve crush injury in order to test the simulations of the mathematical model. The vasculature in both the chamber and following nerve crush responded as predicted by the model, increasing beyond normal levels to a peak only to decrease back to normal. This behavior appeared as a traveling wave in the proximal-distal direction preceeding the major thrust of neuritic outgrowth suggesting that development of the vasculature is a rate-limiting step in nerve regeneration.

Animals↗