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PubMed1989

Direct diffusion of cis-diamminedichloroplatinum(II) in intraperitoneal rat tumors after intraperitoneal chemotherapy: a comparison with systemic chemotherapy.

Chemotherapy i.p. is increasingly being tested as a treatment modality for cancer limited to the peritoneal cavity. We have developed a rat tumor model in which penetration and distribution of cis-diamminedichloroplatinum(II) into intraperitoneal tumors have been studied. The platinum concentration in intraperitoneal tumor nodules, measured by two techniques, flameless atomic absorption spectroscopy and proton-induced X-ray emission, was always higher after i.p. treatment than i.v. Further, platinum concentrations were higher at the periphery of the tumor after i.p. administration than after i.v., while platinum concentrations in the center of the tumor nodules were identical. No difference was detected in platinum concentrations in s.c. tumors nor in the total area under the curve (plasma) after i.p. and i.v. administration of cis-diamminedichloroplatinum(II), suggesting that the higher drug concentration measured in peritoneal tumors after i.p. administration is due to direct diffusion of the drug from the peritoneal cavity.

Adenocarcinoma↗
PubMed1976

Influence of membrane lipid fluidity on glucose and uridine facilitated diffusion in human erythrocytes.

A central question which must be resolved before acceptable molecular descriptions of facilitated diffusion systems can be provided is the nature of the spatial and functional relationships between the transport proteins and the membrane lipids. In the work reported here, this question was addressed by investigating the dependence of the rates of glucose and uridine facilitated diffusion in human erythrocytes on membrane lipid fluidity. Two approaches were used to alter the lipid fluidity: treatment with ether, an anesthetic, and the exchange of a synthetic 3-ketosteroid, cholest-4-en-3-one, for membrane chloesterol. Both of these treatments result in a significant increase in membrane lipid fluidity, as judged by the increase in the rates of passive diffusion of uridine through cell membranes and of glucose through membrane lipid bilayer vesicles. Ether produces no change in the Km of either transport process, a slight decrease in the V for glucose transport, and no significant change in the V for uridine transport. Replacement of membrane cholesterol by cholest-4-en-3-one reduces the V for glucose transport slightly, without altering the Km, and reduces both the Km and V for uridine transport. The absence of the expected increase in the V of facilitated diffusion with increasing membrane lipid fluidity observed here with human erythrocytes is not consistent with models for the transport process which feature movement of transport proteins which are in direct contact with the bulk lipids of the membrane.

Biological Transport↗
PubMed1977

Influence of isoproterenol and cholestyramine on acute gastric mucosal ulcerogenesis.

One thesis concerning the pathogenesis of "stress ulcer" states that the combination of (1) bile acid-induced H+ "back diffusion" and (2) gastric mucosal ischemia is acutely Hg) to induce ischemia, this thesis was further tested by selectively mitigating either the ischemic or the back diffusion components of the model. Vascularized wedges of proximal canine gastric wall mounted on Lucite chambers were studied. With the mucosa directly visualized, control group A (6 dogs) was subjected sequentially to (1) topical acid test solution alone (ATS), (2) ATS + S, and (3) ATS + S + topical 5 mM Na taurocholate (TC). Study group B (6 dogs): (1) ATS, (2) ATS + S + the beta adrenergic agonist, isoproterenol, 1.5 microng per kg-min infused into the splenic artery, and (3) ATS + S + TC + isoproterenol. Study group C (6 dogs): (1) ATS, (2) ATS + S + the bile acid binding resin, cholestyramine (C), 4 g per liter, and (3) ATS + S + TC + C. During each period the net flux of H+, the electrical potential difference, and the aminopyrine clearance (AC) were determined. Mucosal damage (intramucosal hemorrhage, erosions, and ulcers, graded 0 to 5) was assessed blindly by an independent observer using photographs. The results indicate (1) that, despite H+ back diffusion comparable to ATS + S + TC, intraarterial isoproterenol significantly protects against lesion formation by increasing AC, and (2) that, despite a reduction in AC comparable to ATS + S + TC, topical C significantly protects against lesion formation by preventing excessive back diffusion of H+.

Administration, Topical↗
PubMed2003

A diffusion-based theory of organism dispersal in heterogeneous populations.

We develop a general theory of organism movement in heterogeneous populations that can explain the leptokurtic movement distributions commonly measured in nature. We describe population heterogeneity in a state-structured framework, employing advection-diffusion as the fundamental movement process of individuals occupying different movement states. Our general analysis shows that population heterogeneity in movement behavior can be defined as the existence of different movement states and among-individual variability in the time individuals spend in these states. A presentation of moment-based metrics of movement illustrates the role of these attributes in general dispersal processes. We also present a special case of the general theory: a model population composed of individuals occupying one of two movement states with linear transitions, or exchange, between the two states. This two-state "exchange model" can be viewed as a correlated random walk and provides a generalization of the telegraph equation. By exploiting the main result of our general analysis, we characterize the exchange model by deriving moment-based metrics of its movement process and identifying an analytical representation of the model's time-dependent solution. Our results provide general and specific theoretical explanations for empirical patterns in organism movement; the results also provide conceptual and analytical bases for extending diffusion-based dispersal theory in several directions, thereby facilitating mechanistic links between individual behavior and spatial population dynamics.

Animal Migration↗
PubMed1996

Determination of intraparticulate mass transfer coefficients via permeation measurements: theory and experimental validation.

A mathematical model of mass transfer through a heterogeneous, multiphase barrier has been developed where the dispersed phase is capable of uptake of the diffusant according to a linear relationship. The model was used to describe the penetration of drugs through dispersions of permeable globules in media of known diffusional properties. Water-in-oil-in-water (W/O/W) multiple emulsions have been studied by this method. When used to analyze data obtained with a simple diffusion cell, the model allows the calculation of the mass transfer coefficient which characterizes the diffusional mass transfer across oil-water interfaces within the emulsions. The mass transfer coefficient is directly related to the drug release rate from the internal phases of multiple emulsions. Those cases where instantaneous equilibria are established or where impermeable globules are present can be treated as special limiting cases. Differential equations which express diffusant concentrations as functions of time, space, and dispersion system parameters have been solved by Laplace transformation without recourse to numerical methods. The values of the mass transfer coefficient are shown to reflect the physical characteristics of multiple emulsion systems.

Antimetabolites↗
PubMed1988

Morphology and morphometry of the normal lung of the adult vervet monkey (Cercopithecus aethiops).

The lungs of four adult specimens of the vervet monkey (Cercopithecus aethiops) have been examined by transmission and scanning electron microscopy. A morphometric evaluation of the structural components directly involved in gas exchange has been carried out and the data have been modelled to estimate the anatomical diffusing capacity of the lung. The upper air-conducting airways of the lung were lined by an epithelium characterized by ciliated cells among which were dispersed goblet cells. The alveolar surface was lined by squamous type I pneumocytes and cuboidal type II granular pneumocytes. The blood-gas (tissue) barrier consisted of an epithelial cell, a common basal lamina, and an endothelial cell in the thin parts of the interalveolar septum. In the thicker parts of the septum, an interstitial space interposed between the basal laminae of the epithelial and endothelial cells contained supportive elements such as collagen, elastic tissue, and fibrocytes. The alveoli, the blood capillaries, and septal tissue composed 73%, 16%, and 11%, respectively, of the parenchyma. The harmonic and arithmetic mean thicknesses of the blood-gas (tissue) barrier were 0.311 micron and 1.048 microns; the surface area of the blood-gas (tissue) barrier per unit body weight was 50 cm2g-1, and the surface density was 117 mm2.mm3-1. The weight-specific total morphometric diffusing capacity was 0.11 mlO2 (sec.mbar.kg)-1. In comparison, the pulmonary morphometric characteristics of vervet monkey lung were superior to those of the other primates (Macaca irus, M. mulatta, and Homo sapiens) for which equivalent data are available. The gas-exchange potential of the lungs of the nonhuman primates as revealed by morphometric studies surpasses that of man, a feature that can be attributed to the relatively less energetic human lifestyle.

Animals↗
PubMed2005

Evaluation of particle translocation across the alveolo-capillary barrier in isolated perfused rabbit lung model.

Particulate air pollution is associated with respiratory and cardiovascular morbidity and mortality. It has been suggested that ultrafine particles are able to translocate from the airways into the bloodstream in vivo. We have investigated this in an isolated perfused and ventilated rabbit lung preparation lacking pulmonary lymphatic flow. Fluorescent polystyrene particles of different diameters (24, 110 or 190 nm) and surface chemistry (carboxylate or amine modified) were injected either intratracheally (i.t.) or intravascularly (i.v.) and, after a period of 2 h, their presence in the perfusion liquid or in the bronchoalveolar lavage (BAL) fluid, was assessed by spectrofluorimetry. Vascular pressures and lung weights were monitored. Following the i.t. administration, no particle translocation was observed from the alveoli into the vascular compartment. Similarly, no particle translocation was found after i.v. administration of particles. However, when microvascular permeability was pharmacologically increased by administering histamine (10(-4) M) in the vascular compartment, inducing a positive driving force provided by fluid filtration, a fluorescent signal in BAL was recorded (2.5 +/- 1% of the dose of particles administered), suggesting a translocation of particles through the alveolo-capillary barrier. We conclude that ultrafine polystyrene particles cannot significantly diffuse from lung into the vascular compartment in our model, but they are able to translocate in the opposite direction when the microvascular permeability is increased by histamine. The relevance of these ex vivo findings for the in vivo translocation of inhaled ultrafine particles remains to be established.

Air Pollutants↗
PubMed1974

Restricted transport in small pores. A model for steric exclusion and hindered particle motion.

The basic hydrodynamic equations governing transport in submicron pores are reexamined. Conditions necessary for a simplified, one-dimensional treatment of the diffusion/convection process are established. Steric restrictions and Brownian motion are incorporated directly into the resulting model. Currently available fluid mechanical results are used to evaluate an upper limit on hindered diffusion; this limit is valid for small particle-to-pore ratios. Extensions of the analysis are shown to depend on numerical solutions of the related hydrodynamic problem, that of asymmetrical particle motion in a bounded fluid.

Biological Transport↗
PubMed2002

A new approximate whole boundary solution of the Lamm differential equation for the analysis of sedimentation velocity experiments.

Sedimentation velocity is one of the best-suited physical methods for determining the size and shape of macromolecular substances or their complexes in the range from 1 to several thousand kDa. The moving boundary in sedimentation velocity runs can be described by the Lamm differential equation. Fitting of suitable model functions or solutions of the Lamm equation to the moving boundary is used to obtain directly sedimentation and diffusion coefficients, thus allowing quick determination of size, shape and other parameters of macromolecules. Here we present a new approximate whole boundary solution of the Lamm equation that simultaneously allows the specification of sedimentation and diffusion coefficients with deviations smaller than 1% from the expected values.

Algorithms↗
PubMed2001

Magnetic resonance imaging of molecular transport in living morning glory stems.

MRI was applied to investigate the transport pathways in Morning Glory plant stems. The study was carried out on living plants without affecting their integrity. The architecture of a dicotyledonous plant was deeply characterized: the root system structure and the vascular bundle location were identified, the presence of central voids caused by cell maturation and loss were observed in the stem. Molecular transport components were recognized, by observing the concentration profile of a tracer, which changed with time after its absorption by the plant roots. MRI analysis revealed the presence of an axial transport as the progress of the tracer front through the vascular bundles and a radial molecular transport from the vascular bundles toward the surface of the stem. As a result, the tracer molecular transport formed the parabolic tracer front (PTF). A model was built up through the analysis of the PTF that consisted of an axial front at the peak position and a radial front at the width of the parabolic tail. PTF analysis revealed differences between the tracer transport velocities in the axial and the radial directions in the plant stem. The model revealed that the width of the parabolic tail reflected the magnitudes of diffusion and permeation of the tracer in the plant stem.

Biological Transport↗
PubMed2003

There is more to anger coping than "in" or "out".

There is growing dissatisfaction with a dichotomized "anger-in" versus "anger-out" view of anger coping. Three studies using student and community adultsamples revealed a broader understanding of the nature of anger coping styles and led to the development of the new Behavioral Anger Response Questionnaire (BARQ). The BARQ is empirically derived and factorially validated and has good psychometrics. Results suggest that dichotomizing anger responses as "in" versus "out" is too coarse and that a 6-factor model may be more appropriate. The 6 factors identified here are Direct Anger-Out, Assertion, Support-Seeking, Diffusion, Avoidance, and Rumination. Women reported use of a wider range of anger coping styles, especially more social support-seeking and more use of anger diffusion strategies than men.

Adaptation, Psychological↗
PubMed1993

Primary tumors of the lung other than lung cancer.

Neoplasms of the lung other than lung cancer are rare and have varying biologic behavior. Diffuse malignant mesothelioma remains a difficult clinical problem, with efforts directed at combined modality therapy. A nude mouse xenograft model may hold promise in the identification of active chemotherapy agents. Continuing evidence suggests that typical and atypical pulmonary carcinoids represent a spectrum of neuroendocrine disease, with small cell lung cancer representing the most virulent subtype. Therapy for advanced invasive thymoma includes neoadjuvant chemotherapy, surgery, and postoperative radiation. Nonseminomatous germ cell neoplasms of the mediastinum respond much less favorably to cisplatin-based chemotherapy than do similar tumors arising elsewhere, and new advances in treatment are needed. Rare mesenchymal tumors usually respond favorably to surgical excision.

Animals↗
PubMed2005

Upscaling and reversibility of Taylor dispersion in heterogeneous porous media.

Tracer flow in stratified porous media is dominated by the interaction between convective transport and transverse diffusive mixing. By averaging the tracer concentration in the transverse direction, a one-dimensional non-Fickian dispersion model is derived. The model accounts for the relaxation process that reduces the convective transport to dispersive mixing. This process is (short-) time correlated and partially reversible upon reversal of flow direction. For multiscale velocity fields, the relaxation is a multiscale process. To date only single scale processes have been successfully upscaled. Our procedure extends this to multiscale processes, using scale separation. The model parameters can be calculated a priori based on the velocity profile. For periodic flow reversal, the results are essentially the same. Despite the non-Fickian behavior during a cycle, the net contribution of each cycle to the spreading relaxes to a Fickian process in a similar way as for unidirectional flow. The cycle time averaged dispersion coefficient is a monotonically increasing function of the reversal time. It asymptotically converges towards the effective dispersion coefficient in the absence of flow reversal.

Journal Article↗
PubMedDate not supplied

Effect of errors in baseline optical properties on accuracy of transabdominal near-infrared spectroscopy in fetal sheep brain during hypoxic stress.

A continuous-wave (cw) near-infrared spectroscopy (NIRS) instrument has been developed to noninvasively quantify fetal cerebral blood oxygen saturation (StO2). A linear Green's function formulism was used to analytically solve the photon diffusion equation and extract the time-varying fetal tissue oxy- and deoxy-hemoglobin concentrations from the NIR measurements. Here we explored the accuracy with which this instrument can be expected to perform over a range of fetal hypoxic states. We investigated the dependence of this accuracy on the accuracy of the reference optical properties chosen based on the literature. The fetal oxygenation of a pregnant ewe model was altered via maternal aortic occlusion. The NIR cw instrument was placed on the maternal abdomen directly above the fetal head, continuously acquiring diffuse optical measurements. Blood was sampled periodically from the fetus to obtain fetal arterial saturation (SaO2) measurements from blood gas analysis. The NIR StO2 values were compared with the fetal SaO2 measurements. Variations in the NIR results due to uncertainty in the reference optical properties were relatively small within the fetal SaO2 range of 30 to 80%. Under hypoxic conditions, however, the variability of the NIR StO2 calculations with changes in the assumed reference properties became more significant.

Abdomen↗
PubMed2000

Mechanism of receptor-oriented intercellular calcium wave propagation in hepatocytes.

Intercellular calcium signals are propagated in multicellular hepatocyte systems as well as in the intact liver. The stimulation of connected hepatocytes by glycogenolytic agonists induces reproducible sequences of intracellular calcium concentration increases, resulting in unidirectional intercellular calcium waves. Hepatocytes are characterized by a gradient of vasopressin binding sites from the periportal to perivenous areas of the cell plate in hepatic lobules. Also, coordination of calcium signals between neighboring cells requires the presence of the agonist at each cell surface as well as gap junction permeability. We present a model based on the junctional coupling of several hepatocytes differing in sensitivity to the agonist and thus in the intrinsic period of calcium oscillations. In this model, each hepatocyte displays repetitive calcium spikes with a slight phase shift with respect to neighboring cells, giving rise to a phase wave. The orientation of the apparent calcium wave is imposed by the direction of the gradient of hormonal sensitivity. Calcium spikes are coordinated by the diffusion across junctions of small amounts of inositol 1,4, 5-trisphosphate (InsP(3)). Theoretical predictions from this model are confirmed experimentally. Thus, major physiological insights may be gained from this model for coordination and spatial orientation of intercellular signals.-Dupont, G., Tordjmann, T., Clair, C., Swillens, S., Claret, M., Combettes, L. Mechanism of receptor-oriented intercellular calcium wave propagation in hepatocytes.

Animals↗
PubMed2006

Nonlinear multiscale wavelet diffusion for speckle suppression and edge enhancement in ultrasound images.

This paper introduces a novel nonlinear multiscale wavelet diffusion method for ultrasound speckle suppression and edge enhancement. This method is designed to utilize the favorable denoising properties of two frequently used techniques: the sparsity and multiresolution properties of the wavelet, and the iterative edge enhancement feature of nonlinear diffusion. With fully exploited knowledge of speckle image models, the edges of images are detected using normalized wavelet modulus. Relying on this feature, both the envelope-detected speckle image and the log-compressed ultrasonic image can be directly processed by the algorithm without need for additional preprocessing. Speckle is suppressed by employing the iterative multiscale diffusion on the wavelet coefficients. With a tuning diffusion threshold strategy, the proposed method can improve the image quality for both visualization and auto-segmentation applications. We validate our method using synthetic speckle images and real ultrasonic images. Performance improvement over other despeckling filters is quantified in terms of noise suppression and edge preservation indices.

Algorithms↗
PubMed1986

In vitro measurement and computer modelling of the diffusion of antibiotic in bone cement.

The diffusion coefficient for a particular antibiotic (benzyl penicillin) in various types of bone cement has been calculated from direct measurement of the passage of radio-labelled penicillin through thin sections of cement at intervals over a period of 90 days, assuming the transport processes to be Fickian. Since the concentration gradient across the test sample is not uniform in the earlier stages of the experiment, a finite-difference approximation to the diffusion equation was used to take account of the transient behaviour in determining the coefficient. This method of analysis may also be used to predict the release, as a function of time, from the surface of antibiotic-loaded bone cement and from implanted pre-loaded PMMA beads used to provide antibiotic cover following bone or joint surgery. Our computer-generated predictions appear to agree very well with previously published figures arising from in vivo and in vitro studies and we conclude therefore, that Fick's Law accurately describes the process, even when the cement mix is inhomogeneous. We have by this means a reliable method by which the diffusion coefficients for various combinations of cement, antibiotic and other additives may be retrospectively determined and compared.

Anti-Bacterial Agents↗
PubMedDate not supplied

Prediction of diffusion coefficients in porous media using tortuosity factors based on interfacial areas.

Determination of aqueous phase diffusion coefficients of solutes through porous media is essential for understanding and modeling contaminant transport. Prediction of diffusion coefficients in both saturated and unsaturated zones requires knowledge of tortuosity and constrictivity factors. No methods are available for the direct measurement of these factors, which are empirical in their definition. In this paper, a new definition for the tortuosity factor is proposed, as the real to ideal interfacial area ratio. We define the tortuosity factor for saturated porous media (tau5) as the ratio S/S(o) (specific surface of real porous medium to that of an idealized capillary bundle). For unsaturated media, tortuosity factor (tau(a)) is defined as a(aw)/a(aw),o (ratio of the specific air-water interfacial area of real and the corresponding idealized porous medium). This tortuosity factor is suitably measured using sorptive tracers (e.g., nitrogen adsorption method) for saturated media and interfacial tracers for unsaturated media. A model based on this new definition of tortuosity factors, termed the interfacial area ratio (IAR) model, is presented for the prediction of diffusion coefficients as a function of the degree of water saturation. Diffusion coefficients and diffusive resistances measured in a number of saturated and unsaturated granular porous media, for solutes in dilute aqueous solutions, agree well with the predictions of the IAR model. A comparison of permeability of saturated sands estimated based on tau(s) and the same based on the Kozeny-Carman equation confirm the usefulness of the tau(s) parameter as a measure of tortuosity.

Diffusion↗