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PubMed1999

HPMC-matrices for controlled drug delivery: a new model combining diffusion, swelling, and dissolution mechanisms and predicting the release kinetics.

PURPOSE: The purpose of this study was to investigate the drug release mechanisms from hydroxypropyl methylcellulose (HPMC)-matrices, and to develop a new model for quantitative predictions of controlled drug delivery. METHODS: The dissolved mass of pure HPMC-matrices and the drug release rate from propranolol HCl-loaded HPMC-matrices were determined experimentally. Based on Fick's second law of diffusion for cylinders, the transport of water and drug were modeled considering (i) both radial and axial diffusion, (ii) concentration-dependent drug diffusivities, (iii) matrix swelling and (iv) HPMC dissolution. RESULTS: Good agreement between theory and experiment (dissolved mass and drug release studies) was obtained, proving the validity of the presented model. The water and drug diffusivities are strongly dependent on the matrix swelling ratio. Diffusion, swelling and dissolution are the governing mechanisms involved in the overall drug release process. CONCLUSIONS: The practical benefit of the presented model is to identify the required shape and dimensions of drug-loaded HPMC-matrices in order to achieve desired release profiles, thus facilitating the development of new controlled drug delivery products. This will be demonstrated in a future study.

Delayed-Action Preparations↗
PubMed2004

Influence of a depletion interaction on dynamical heterogeneity in a dense quasi-two-dimensional colloid liquid.

We report the results of digital video microscopy studies of the large particle displacements in a quasi-two-dimensional binary mixture of large (L) and small (S) colloid particles with diameter ratio sigma(L)/sigma(S)=4.65, as a function of the large and small colloid particle densities. As in the case of the one-component quasi-two-dimensional colloid system, the binary mixtures exhibit structural and dynamical heterogeneity. The distribution of large particle displacements over the time scale examined provides evidence for (at least) two different mechanisms of motion, one associated with particles in locally ordered regions and the other associated with particles in locally disordered regions. When rhoL*=Npisigma(L) (2)/4A< or =0.35, the addition of small colloid particles leads to a monotonic decrease in the large particle diffusion coefficient with increasing small particle volume fraction. When rhoL* > or =0.35 the addition of small colloid particles to a dense system of large colloid particles at first leads to an increase in the large particle diffusion coefficient, which is then followed by the expected decrease of the large particle diffusion coefficient with increasing small colloid particle volume fraction. The mode coupling theory of the ideal glass transition in three-dimensional systems makes a qualitative prediction that agrees with the initial increase in the large particle diffusion coefficient with increasing small particle density. Nevertheless, because the structural and dynamical heterogeneities of the quasi-two-dimensional colloid liquid occur within the field of equilibrium states, and the fluctuations generate locally ordered domains rather than just disordered regions of higher and lower density, it is suggested that mode coupling theory does not account for all classes of relevant fluctuations in a quasi-two-dimensional liquid.

Journal Article↗
PubMed1999

Selectivity and permeation in calcium release channel of cardiac muscle: alkali metal ions.

Current was measured from single open channels of the calcium release channel (CRC) of cardiac sarcoplasmic reticulum (over the range +/-180 mV) in pure and mixed solutions (e.g., biionic conditions) of the alkali metal ions Li+, K+, Na+, Rb+, Cs+, ranging in concentration from 25 mM to 2 M. The current-voltage (I-V) relations were analyzed by an extension of the Poisson-Nernst-Planck (PNP) formulation of electrodiffusion, which includes local chemical interaction described by an offset in chemical potential, which likely reflects the difference in dehydration/solvation/rehydration energies in the entry/exit steps of permeation. The theory fits all of the data with few adjustable parameters: the diffusion coefficient of each ion species, the average effective charge distribution on the wall of the pore, and an offset in chemical potential for lithium and sodium ions. In particular, the theory explains the discrepancy between "selectivities" defined by conductance sequence and "selectivities" determined by the permeability ratios (i.e., reversal potentials) in biionic conditions. The extended PNP formulation seems to offer a successful combined treatment of selectivity and permeation. Conductance selectivity in this channel arises mostly from friction: different species of ions have different diffusion coefficients in the channel. Permeability selectivity of an ion is determined by its electrochemical potential gradient and local chemical interaction with the channel. Neither selectivity (in CRC) seems to involve different electrostatic interaction of different ions with the channel protein, even though the ions have widely varying diameters.

Animals↗
PubMed2002

The effect of obstacle conductivity and electric field on effective mobility and dispersion in electrophoretic transport: a volume averaging approach.

The method of volume averaging has been used to determine the effective electrophoretic mobility and dispersion coefficients for molecular transport of point-like solutes in a two-phase porous medium where the electrical conductivity and the diffusion and mobility coefficients may vary in both phases. The formal theory, derived in previous work, is numerically evaluated for cases where the obstacle phase has a large or small conductivity relative to the fluid phase and where the diffusion coefficient of the solute in the obstacle phase can be large or small relative to that in the fluid phase. In agreement with previous Monte Carlo methods, the effective electrophoretic mobility is not a function of media conductivity or electric field when the obstacles are impermeable to solute transport or have small diffusion solute diffusion coefficients. However, the dispersion coefficient is a strong function of electric field and varies with obstacle conductivity when diffusive transport is small in the obstacles relative to the fluid. In contrast, the effective electrophoretic mobility is a function of electric field when conductivity of the obstacles is much larger than the fluid and when the obstacles are very permeable to solute but have low electrical conductivity.

Electric Conductivity↗
PubMed1996

Line-scanning microphotolysis for diffraction-limited measurements of lateral diffusion.

Fluorescence microphotolysis was combined with confocal laser-scanning microscopy to yield a method, herein referred to as line-scanning microphotolysis (LINESCAMP), for the measurement of molecular transport at a lateral resolution of approximately 0.34 microns and a temporal resolution of approximately 0.5 ms. A confocal microscope was operated in the line scan mode, while the laser beam power could be switched during scanning between low monitoring and high photolysing levels in less then a microsecond. The number and location of line segments to be photolysed could be freely determined. The length of the photolysed segments could be also chosen and was only limited by diffraction. Together with instrumentation a new, completely general, theoretical framework for the evaluation of diffusion measurements was developed. Based on the numerical simulation of diffusion processes employing a modified Crank-Nicholson scheme, the theory could be applied to any photobleaching geometry and profile as the initial condition and took into account the convolution with the microscope point spread function. With small diffraction-limited areas, the method yielded accurate values for diffusion coefficients in the range between approximately 10(-4) and 1 micron2 s-1. A first application of the method to the diffusion of a fluorescently labeled tracer inside the cell nucleus showed the potential of the method for the study of complex biological systems.

3T3 Cells↗
PubMed2006

[A research on iteration stopping time of anisotropic diffusion].

Anisotropic diffusion has good effect on reducing noise and preserving edge, in fact it's an iterative process. An important question is to decide when the process should be stopped. The stopping time is chosen by minimal mean square error, signal-to-noise ratio and minimal correlation coefficient based on the information of the original (ideal) images and noises. The entropy and mutual information in information theory is adopted to develop a criterion on stopping diffusion process. The performance of the different criterions is proved by experiments, the specialty and the applying condition is also discussed.

Anisotropy↗
PubMed2002

T(2)-shortening by strongly magnetized spheres: a chemical exchange model.

It is shown that a chemical exchange model can reproduce nuclear magnetic relaxation caused by diffusion of water molecules near strongly magnetized particles. The agreement is based on the similarity (but not equivalence) of the respective "visit-limiting" mechanisms in the echo-limited regime. The model leads to a single equation that predicts relaxation behavior in both the motional-averaging and visit-limited regimes. When combined with the static-dephasing regime equation, the result is a simple theory (for spheres) that covers the entire range of diffusion times.

Diffusion↗
PubMed2005

Survival probability of diffusion with trapping in cellular neurobiology.

The problem of diffusion with absorption and trapping sites arises in the theory of molecular signaling inside and on the membranes of biological cells. In particular, this problem arises in the case of spine-dendrite communication, where the number of calcium ions, modeled as random particles, is regulated across the spine microstructure by pumps, which play the role of killing sites, while the end of the dendritic shaft is an absorbing boundary. We develop a general mathematical framework for diffusion in the presence of absorption and killing sites and apply it to the computation of the time-dependent survival probability of ions. We also compute the ratio of the number of absorbed particles at a specific location to the number of killed particles. We show that the ratio depends on the distribution of killing sites. The biological consequence is that the position of the pumps regulates the fraction of calcium ions that reach the dendrite.

Animals↗
PubMed1976

The permeability of lung capillary and alveolar walls as determinants of liquid movements in the lung.

The lungs of the exteriorized fetal lamb offer an unusually good opportunity for measuring the permeability of lung capillary and alveolar walls, because access to plasma, interstitial fluid and alveolar liquid can be obtained without seriously disturbing their physiological relationships. Although there are probably some differences in permeability between fetal and air-breathing lungs, the underlying pattern appears to be similar. Large water-soluble molecules, including proteins, can penetrate capillary but not alveolar walls. The latter appear to be impermeable to molecules with diffusion radii greater than 0.5-0.6 nm. Pore theory can be used to characterize these permeabilities and to obtain estimates of osmotic reflection coefficients for various water-soluble substances. From them, predictions can be made of the bulk movements of liquid to be expected in a variety of circumstances, including the adaptation of the lungs at birth, lung oedema and drowning in sea water or fresh water.

Animals↗
PubMed1987

Role of Na-K ATPase in regulation of resting membrane potential of cultured rat skeletal myotubes.

The role of Na-K ATPase in the determination of resting membrane potential (Em) as a function of extracellular K ion concentration was investigated in cultured rat myotubes. The Em of control myotubes at 37 degrees C varied as a function of (K+)0 with a slope of about 58-60 mV per ten-fold change in (K+)0. Inhibition of the Na-K pump with ouabain or by reduced temperature revealed that this relation consists of two components. One, between (K+)0 of 10 and 100 mM, remains unchanged by alterations in enzyme activity; The second, between (K+)0 of 1 and 10 mM, is related to the amount of Na-K pump activity, the slope decreasing as pump activity decreases. Indeed, with complete inhibition of the Na-K pump, Em does not change over the range of (K+)0 1 to 10 mM. Measurements of 86Rb efflux and input resistance of individual myotubes showed that membrane permeability does not change as (K+)0 increases from 1 to 10 mM but increases as (K+)0 increases further. Monensin, which increases Na ion permeability, increases Em at values of external K+ below 10 mM, and is without effect at higher values of K+ concentration. The effect of monensin is blocked by ouabain. Tetrodotoxin, which blocks voltage-dependent Na+ channels, decreases Em at low (2-10 mM) K+. We conclude that changes in Em as a function of extracellular K+ concentration in the physiological range are not adequately explained by the diffusion potential hypothesis of Em, and that other theories (electrogenic pump, surface-absorption) must be considered.

Animals↗
PubMed2000

A Generalized Model for Describing Particle Formation in the Synthesis of Monodisperse Oxide Particles Based on the Hydrolysis and Condensation of Tetraethyl Orthosilicate.

A generalized model considering reaction and diffusion processes as rate determining steps is proposed for the formation of particles from hydrolysis and condensation of tetraethyl orthosilicate (TEOS). Reaction rate constant is assumed to be proportional to contact-surface area of two particles. Diffusion rate constant is given by Fuchs' stability theory with interparticle potential containing van der Waals attraction and electrostatic repulsion. To examine the validity of the model, ammonia-catalyzed reactions of TEOS were carried out in an ethanol-water solution at a water concentration of 11 mol/dm(3), an ammonia concentration of 1.0 mol/dm(3), and TEOS concentrations of 0.2 and 0.4 mol/dm(3) in the presence and in the absence of electrolytes. The experiments included competitive particle growth and seeded and nonseeded reactions. The model quantitatively expressed the results of the competitive growth experiments in which particles with different sizes grew at the same rate. The model gave the expected trend for the effect of ionic strength on particle sizes in the nonseeded reaction and the suppression of secondary particles in the seeded reaction by the addition of an electrolyte KCl. Good estimation was also obtained for transient particle size distributions in the nonseeded reaction and the seeded reaction in which secondary particles were generated. Copyright 2000 Academic Press.

Journal Article↗
PubMed2001

Dephasing relaxation of the electron spin echo of the vibronic Cu(H(2)O)(6) complexes in Tutton salt crystals at low temperatures.

Two-pulse electron spin echo (ESE) measurements of the phase relaxation (phase memory time T(M)) were performed in a series of Tutton salt crystals M(I)(2)M(II)(SO(4))(2).6X(2)O (M(I)=NH(4), K, Cs; M(II)=Zn, Mg; X=H, D) weakly doped with Cu(2+) ions (c approximately equal to 10(18) ions/cm(3)) in temperature range 4-60 K where ESE signals were detectable. The ESE decay was strongly modulated with proton (or deuteron) frequencies and described by the decay function V(2tau)=V(0)exp(-btau-mtau(2)) with the mtau(2) term being temperature independent and negligible above 20 K. Various mechanisms leading to the tau- or tau(2)-type ESE decay are reviewed. The m and b coefficients for nuclear spectral diffusion (NSD), electron spectral diffusion (SD), and instantaneous diffusion (ID) were calculated in terms of existing theories and the resulting rigid lattice T(0)(M) times were found to be close one to another within the crystal family with average values: 17.5 micros (NSD protons), 200 micros (NSD deuterons), 8 micros (SD), and 5 micros (ID). The ID dominates but the calculated effective T(M)(0) is longer than the experimental T(M)(0)=2 micros. This is due to a nonuniform distribution of the Cu(2+) ions with a various degree of the disorder in the studied crystals. The acceleration of the dephasing rate 1/T(M) with temperature is due to the mechanisms producing exp(-btau) decay. They are reviewed and two of them were found to be operative in Tutton salt crystals: (a) Excitations to the vibronic levels of energy Delta leading to the temperature dependence 1/T(M)=B exp(-Delta/kT), with the vibronic levels produced by strong Jahn-Teller effect, and (b) spin-lattice relaxation processes being effective above 50 K. Based on the Delta values being on the order of 100 cm(-1), the scheme of vibronic levels in the Tutton salts is presented, and the independence of the Delta on temperature proves that the adiabatic potential surface shape of Jahn-Teller active Cu(H(2)O)(6) complexes is not affected by temperature below 65 K.

Journal Article↗
PubMed1991

On the role of gravity and positional information in embryological axis formation and tissue compartmentalization.

The idea that gravity affects dorso-ventral polarization in anouran development contrasts with the theories of self-organization through reaction-diffusion processes. As a result of a literature study we discuss the role of gravity in embryological axis formation and speculate on an influence of gravity on tissue compartmentalization. The involvement of compartmentalization in tissue homeostasis is discussed in the light of the recent progress in mammalian cell culture studies.

Amphibians↗
PubMed1986

The diffusion of medical technology: a "prisoner's dilemma" trap?

Medical technology diffusion and its effect on the modern hospital and on the rising costs of medical care is an issue which receives considerable attention from economists and policy analysts. In this paper a different approach is used to understand this phenomenon. We present the decision of a single hospital, whether or not to adopt an advanced technology system, using the concept of a noncooperative, nonzero sum game. Such presentation provides us with more insight on the conflict in which hospitals find themselves; the "catch" which pushes them to purchase more and more sophisticated and expensive technology in the hope that they will be able to successfully compete with other hospitals. The situation is further complicated by the existence of another "hidden" player--society, whose goals may differ from those of any individual hospital and even from the collective interests of the hospital sector. Possible conflicts that may exist and suggested solutions for each participant are presented and their policy implication are discussed.

Communication↗
PubMed1987

Theory and delivery of health programming in the community: the Pawtucket Heart Health Program.

The Pawtucket Heart Health Program is one of the community studies examining whether population-based efforts to lower cardiovascular risk factors will reduce cardiovascular morbidity and mortality. The Pawtucket Heart Health Program intervention is based on a blend of social learning theory, community organization models, community psychology tenets, and diffusion research. This model allows for multifaceted programs that target individuals, groups, organizations, and the entire community to alter their cardiovascular risk through managing blood pressure, lowering blood cholesterol, quitting smoking, increasing fitness, and maintaining desirable weight levels. A dominant feature of the intervention is the emphasis that it places on volunteers for program delivery. The role of volunteers in providing direct services to help citizens lower their blood pressure and lose weight is highlighted to demonstrate the feasibility and effectiveness of these services. In addition, church-based programming which utilizes volunteers to manage and direct programs is also presented as an example of community-based health promotion efforts that promote collective efficacy.

Adolescent↗
PubMed1991

Study of experimental pain measures and nociceptive reflex in chronic pain patients and normal subjects.

This study evaluates (i) the effect of heterotopic chronic pain on various experimental pain measures, (ii) the relationship between experimental pain measures and chronic pain symptomatology assessment, and (iii) the influence of the various pain aetiologies on experimental pain measures. Fifty-three chronic pain patients were compared to 17 pain-free subjects with the following psychophysical and physiological indices: pain threshold (PTh), pain tolerance (PTol), verbal estimation of intensity and unpleasantness (intensity scale, IS; unpleasantness scale, US), threshold for intensity and unpleasantness (ITh and UTh), lower limb RIII nociceptive reflex (RIIITh and RIII frequency of occurrence). Chronic pain syndromes included neuropathic pain (n = 12), iodopathic pain (n = 12), myofascial syndromes (n = 9), headache (n = 9), and miscellaneous pain (n = 11). Chronic pain symptomatology was assessed with a visual analogue scale (VAS), a French MPQ adaptation (QDSA), Beck Depression Inventory (BDI), Spielberger State Trait Inventory (STAI) and Eysenck Personality Inventory (EPI). No significant difference was observed between chronic pain patients and pain-free control groups and between patient subgroups for PTh, PTol and RIIITh. No significant correlation was found between experimental pain measures and clinical pain, anxiety or depression scores. However, the chronic pain patients had a higher threshold for unpleasantness and judged the suprathreshold stimuli significantly less intense and less unpleasant than the control group. These results are discussed in relation to diffuse noxious inhibitory controls and the adaptation level theory of chronic pain experience.

Adult↗
PubMed1987

A mitochondrial membrane hypothesis of aging.

Recently it has been demonstrated that the loss of water during aging from rat liver and heart muscle tissue is solely due to water loss from the mitochondria. A hypothesis is presented here which shows the relation between free radical attack to, and water loss from, the mitochondria and the decreased energy availability in aged cells. According to it, water loss from the mitochondria is due to an increasing permeability of the inner mitochondrial membrane as a result of its changed composition and, therefore, decreasing osmotic reflexion coefficients for inorganic ions, mainly potassium. The water loss results in limited diffusion of intramitochondrial metabolites and, according to the theory of polyelectrolyte solutions, electrostatic and sterical hindrance of enzymic functions. The hypothesis is in accordance with the well-documented experimental facts, e.g. the lack of structural alterations in mitochondrial DNA and proteins, the constancy of the delta mu H+ and the decrease of state 3 respiration with only a limited number of substrates in mitochondria from old postmitotic cells.

Aging↗
PubMed2005

High-level ab initio thermochemical data for halides of chromium, manganese, and iron.

The thermochemistry of the transition-metal fluorides and chlorides MF(n)() and MCl(n)() (M = Cr, Mn, Fe; n = 1, 2) has been characterized by high-level ab initio electronic structure methods. Geometries and harmonic vibrational frequencies were computed at the B3LYP level of theory using triple-zeta basis sets including diffuse and polarization functions. Heats of formation were computed from isogyric reaction energies at the CCSD(T) level using high-quality basis sets, including corrections for core-valence correlation and scalar relativistic effects. To investigate the possible linearity of the ground states of CrCl(2) and CrF(2), we performed geometry optimizations for these species at the CCSD(T) level using large basis sets. In both cases, a bent ((5)B(2)) minimum structure was located, but the bent structure is only slightly below the linear form, which was found to be a transition state. For all of the investigated halides, polynomial fits were carried out for the heat capacity and the standard enthalpy and entropy in the 300-3000 K temperature range.

Journal Article↗