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Biomedical subjects

P Poulin

Publications and source records attributed to P Poulin.

At least 19 recordsLinked to original sources

An experimental approach to the percolation of sticky nanotubes.

Percolation is a statistical concept that describes the formation of an infinite cluster of connected particles or pathways. Lowering the percolation threshold is a critical issue to achieve light and low-cost conductive composites made of an insulating matrix loaded with conductive particles. This has interest for applications where charge dissipation and electrical conductivity are sought in films, coatings, paints, or composite materials. One route to decreasing the loading required for percolation is to use rod-like particles. Theoretical predictions indicate that this may also be achieved by altering the interaction potential between the particles. Although percolation may not always respond monotonically to interactions, the use of adhesive rods can be expected to be an ideal combination. By using a system made of carbon nanotubes in an aqueous surfactant solution, we find that very small attraction can markedly lower the percolation threshold. The strength of this effect can thereby have direct technological interest and explain the large variability of experimental results in the literature dealing with the electrical behavior of composites loaded with conducting rods.

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Hot-drawing of single and multiwall carbon nanotube fibers for high toughness and alignment.

We report a new hot-drawing process for treating wet-spun composite fibers made of single- and multiwall carbon nanotubes and poly(vinyl alcohol). As shown in previous reports, untreated composite nanotube fibers exhibit a very large strain-to-failure, and their toughness, which is the energy needed to break the fibers, exceeds that of any other known materials. However, untreated composite nanotube fibers absorb a very small amount of energy at low strain and become degraded in humid conditions. In this work, we use hot-drawing treatments, a concept inspired from textile technologies, to improve the properties of nanotube/PVA fibers. This treatment yields a crystallinity increase of the PVA and an unprecedented degree of alignment of the nanotubes. These structural modifications lead to a markedly improved energy absorption at low strain and make the fibers resistant to moisture. Hot-drawn nanotube/PVA fibers hold great potential for a number of applications such as bulletproof vests, protective textiles, helmets, and so forth.

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Colloidal structures from bulk demixing in liquid crystals.

This experimental paper deals with phase separations of binary mixtures composed of a continuous liquid crystal phase and an isotropic dispersed phase. In contrast to isotropic binary mixtures, the investigated mixtures do not lead to a full phase separation but to a self-ordering of colloidal particles, as reported earlier (Loudet, J. C. et al. Nature 2000, 407, 611). We present here further aspects of such phase separations which include the kinetics of the phase separation, the origin of the formation of dislocation-like patterns, the influence of surfactants, chiral additives, and temperature on the formed colloidal structures. The present results show that (i) the dislocations in chain arrays can be seen as kinetically frozen defects, (ii) temperature can be used to control the size of the domains formed upon demixing, (iii) a slight change in surface chemistry, via the addition of surfactants, profoundly alters the formed colloidal structures, and (iv) chiral additives allow the formation of unique helical pearl chains which reflect the symmetry of the liquid crystal phase they are embedded in.

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Stokes drag on a sphere in a nematic liquid crystal.

The Stokes-Einstein relation relates the diffusion coefficient of a spherical Brownian particle in a viscous fluid to its friction coefficient. For a particle suspended in anisotropic liquid, theory predicts that the drag coefficient should also be anisotropic. Using video microscopy coupled with particle tracking routines, the Brownian fluctuations of micrometer-sized particles were analyzed to yield a quantitative measurement of the diffusion coefficients parallel and perpendicular to the nematic director. The experimental values agree quite well with recent numerical calculations that take into account the distortions of the director field in the vicinity of the particles.

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In vivo neuroanatomy of Alzheimer's disease: evidence from structural and functional brain imaging.

In vivo structural (CT, MRI) and functional (SPECT, PET) brain imaging techniques have been widely used to study the neuroanatomy and neurophysiology of Alzheimer's disease (AD) and to identify definite biological markers of the disease. We used meta-analytic methods to synthesize this literature to determine what neuroanatomical structures best differentiate patients with AD from healthy normal controls. A total of 125 studies published between 1984 and 2000 that included 3543 patients with AD and 1698 normal healthy controls met inclusion criteria. We found that measures of the temporal cortices, including the amygdala, hippocampus, and inferior temporal lobes, along with the anterior cingulate cortex, associated with the largest magnitudes of effects and, hence, could serve as the most useful structures to help clinicians differentiate AD from healthy normal aging.

Aged↗

Application of an electric field to colloidal particles suspended in a liquid-crystal solvent.

We study the behavior of colloidal particles suspended in a thermotropic nematic solvent in the presence of an electric field. For normal boundary conditions of the nematic director at the particles' surface, we show experimentally that an electric field applied along the dipolar axis of an elastic dipole induces a transition to an elastic quadrupolar configuration. Turning the field off makes the system go back to the initial state. We also show that it is possible to directly evidence an elastic quadrupolar repulsion between droplets.

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Interactions between colloidal inclusions in two-dimensional smectic-C* films.

We report an experimental study of colloidal inclusions in free-standing films of smectic-C* liquid crystal. The inclusions are cholesteric droplets that form above the bulk smectic-C*-7cholesteric transition temperature. Each droplet confined in a two-dimensional (2D) system, is accompanied by a topological defect. The distortions of the in-plane orientational order of the smectic-C* film induce elastic interactions between the droplets. As in 3D water nematic emulsions, a short-range repulsion and a long-range dipolar attraction govern the stability of the inclusions and lead to their organization in chainlike structures. Our results are in agreement with recent theoretical predictions.

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Molecular structure-based prediction of human abdominal skin permeability coefficients for several organic compounds.

Mechanistically based predictions of skin permeability coefficients (Kp) derived solely on the basis of molecular structure information of organic compounds have not been reported previously. The objective of the present study was to predict the human abdominal Kp of structurally unrelated organic compounds using a mechanistic equation that takes into account compound-specific and species-specific determinants of Kp and relates the compound-specific determinants directly to molecular structure information. The method consisted of obtaining predictions based on a modified form of the conventional equation used to describe Kp (= P x D/L, where P, D, and L represent the stratum corneum:water partition coefficient, diffusion coefficient, and path length of diffusion). The value of P was predicted from the n-octanol:water partition coefficient (Po:w) computed from molecular structure information as well as the lipid, protein, and water contents in stratum corneum. The value of D was predicted according to the conventional Einstein-Stoke equation using the molar volume (Vmolar) of compounds computed from molecular structure information as well as data on viscosity of the stratum corneum components. Finally, the value of L was estimated in accordance with the characteristics of the diffusion pathways in the stratum corneum (i.e., transcellular and intercellular pathways). The average ratio of predicted Kp to the corresponding mean experimental values obtained from the literature was 1.25 (SD = 0.68, r = .95) for 47 structurally unrelated organic compounds (volatile organics and drugs), which were characterized by the presence of less than 2 hydrogen bonding groups and Vmolar < 231 cm3/mol. The present study is the first initiative that permits prediction of the human Kp of organic compounds by using molecular structure information as the sole chemical-specific input in a mechanistic equation.

Abdomen↗

Prediction of adipose tissue: plasma partition coefficients for structurally unrelated drugs.

Tissue:plasma (P(t:p)) partition coefficients (PCs) are important parameters describing tissue distribution of drugs. The ultimate goal in early drug discovery is to develop and validate in silico methods for predicting a priori the P(t:p) for each new drug candidate. In this context, tissue composition-based equations have recently been developed and validated for predicting a priori the non-adipose and adipose P(t:p) for neutral organic solvents and pollutants. For ionizable drugs that bind to different degrees to common plasma proteins, only their non-adipose P(t:p) values have been predicted with these equations. The only compound-dependent input parameters for these equations are the lipophilicity parameter, such as olive oil-water PC (K(vo:w)) or n-octanol-water PC (P(o:w)), and/or unbound fraction in plasma (fu(p)) determined under in vitro conditions. Tissue composition-based equations could potentially also be used to predict adipose tissue-plasma PCs (P(at:p)) for ionized drugs. The main objective of the present study was to modify these equations for predicting in vivo P(at:p) (white fat) for 14 structurally unrelated ionized drugs that bind substantially to plasma macromolecules in rats, rabbits, or humans. The second objective was to verify whether K(vo:w) or P(o:w) provides more accurate predictions of in vivo P(at:p) (i.e., to verify whether olive oil or n-octanol is the better surrogate for lipids in adipose tissue). The second objective was supported by comparing in vitro data on P(at:p) with those on olive oil-plasma PC (K(vo:p)) for five drugs. Furthermore, in vivo P(at:p) was not only predicted from K(vo:w) and P(o:w) of the non-ionized species, but also from K*(vo:w) and P*(o:w), taking into account the ionized species in addition. The P(at:p) predicted from K*(vo:w), P*(o:w), and P(o:w) differ from the in vivo P(at:p) by an average factor of 1.17 (SD = 0.44, r = 0.95), 15.0 (SD = 15.7, r = 0.59), and 40.7 (SD = 57.2, r = 0.33), respectively. The in vitro values of K(vo:p) differ from those of P(at:p) by an average factor of 0.86 (SD = 0.16, r = 0.99, n = 5). The results demonstrate that (i) the equation using only data on fu(p) as input and olive oil as lipophilicity surrogate is able to provide accurate predictions of in vivo P(at:p), and (ii) olive oil is a better surrogate of the adipose tissue lipids than n-octanol. The present study is an innovative method for predicting in vivo fat partitioning of drugs in mammals.

Adipose Tissue↗

Structural characterization of nanotube fibers by x-ray scattering.

Nanotube fibers with diameters ranging between 10 and 100 microns were produced by a simple spinning process. These fibers were studied by x-ray scattering--a technique that allows good visualization of the composition as well as the alignment of the constituents. The fibers were found to be composed of bundles of single wall carbon nanotubes, poly(vinyl alcohol) polymer chains, graphitic objects, and Ni-based particles. The nanotubes and poly(vinyl alcohol) chains were preferentially oriented along the fiber axis.

Catalysis↗

Macroscopic fibers and ribbons of oriented carbon nanotubes.

A simple method was used to assemble single-walled carbon nanotubes into indefinitely long ribbons and fibers. The processing consists of dispersing the nanotubes in surfactant solutions, recondensing the nanotubes in the flow of a polymer solution to form a nanotube mesh, and then collating this mesh to a nanotube fiber. Flow-induced alignment may lead to a preferential orientation of the nanotubes in the mesh that has the form of a ribbon. Unlike classical carbon fibers, the nanotube fibers can be strongly bent without breaking. Their obtained elastic modulus is 10 times higher than the modulus of high-quality bucky paper.

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Colloidal ordering from phase separation in a liquid-crystalline continuous phase

Some binary mixtures exist as a single phase at high temperatures and as two phases at lower temperatures; rapid cooling therefore induces phase separation that proceeds through the initial formation of small particles and subsequent growth and coarsening. In solid and liquid media, this process leads to growing particles with a range of sizes, which eventually separate to form a macroscopically distinct phase. Such behaviour is of particular interest in systems composed of an isotropic fluid and a liquid crystal, where the random distribution of liquid-crystal droplets in an isotropic polymer matrix may give rise to interesting electro-optical properties. Here we report that a binary mixture consisting of an isotropic fluid and a liquid crystal forming the continuous phase does not fully separate into two phases, but self-organizes into highly ordered arrays of monodisperse colloidal droplet chains. We find that the size and spatial organization of the droplets are controlled by the orientational elasticity of the liquid-crystal phase and the defects caused by droplets exceeding a critical size. We expect that our approach to forming monodisperse, spatially ordered droplets in liquid crystals will allow the controlled design of ordered composites that may have useful rheological and optical properties.

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Mitotically active cells that generate neurons and astrocytes are present in multiple regions of the adult mouse hippocampus.

Previous studies of the adult hippocampus of rodents and primates have reported neuro- and gliogenesis restricted to the region of the dentate gyrus. In the present study, by employing a prolonged bromodeoxyuridine (BrdU) labeling protocol that attempts to account for cytokinetic changes as an animal ages, we have identified mitotically active cells in multiple regions of the hippocampus, especially in Ammon's horn, of the adult mouse. Immediately following the labeling period, the BrdU-labeled cells did not express known markers for neurons and astrocytes. Subsequent analysis at 3-24 weeks after labeling demonstrated BrdU-labeled neurons and glia in these regions of the hippocampus. Although neuro- and gliogenesis in the adult mammalian hippocampus have been reported previously, these results demonstrate that the phenomenon is not limited to the region of the dentate gyrus, but rather extends into Ammon's horn. Furthermore, it suggests that ongoing cell production, albeit discrete and limited in nature, may be widespread in the adult mammalian central nervous system.

Age Factors↗

Viscous sintering phenomena in liquid-liquid dispersions.

We present experimental evidence for viscous sintering phenomena in a gel formed by highly viscous emulsion droplets. When a rupturing agent is added to the initially stable emulsion, a gel forms, which further contracts by preserving the geometry of the container. The initial stages of densification (up to 60%) follow very well the "cylindrical model" for viscous sintering, but deviate at the final stages of densification. The observed inverse dependence of the contraction rate on viscosity is consistent with the viscous sintering theory.

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A priori prediction of tissue:plasma partition coefficients of drugs to facilitate the use of physiologically-based pharmacokinetic models in drug discovery.

The tissue:plasma (P(t:p)) partition coefficients (PCs) are important drug-specific input parameters in physiologically based pharmacokinetic (PBPK) models used to estimate the disposition of drugs in biota. Until now the use of PBPK models in early stages of the drug discovery process was not possible, since the estimation of P(t:p) of new drug candidates by using conventional in vitro and/or in vivo methods is too time and cost intensive. The objectives of the study were (i) to develop and validate two mechanistic equations for predicting a priori the rabbit, rat and mouse P(t:p) of non-adipose and non-excretory tissues (bone, brain, heart, intestine, lung, muscle, skin, spleen) for 65 structurally unrelated drugs and (ii) to evaluate the adequacy of using P(t:p) of muscle as predictors for P(t:p) of other tissues. The first equation predicts P(t:p) at steady state, assuming a homogenous distribution and passive diffusion of drugs in tissues, from a ratio of solubility and macromolecular binding between tissues and plasma. The ratio of solubility was estimated from log vegetable oil:water PCs (K(vo:w)) of drugs and lipid and water levels in tissues and plasma, whereas the ratio of macromolecular binding for drugs was estimated from tissue interstitial fluid-to-plasma concentration ratios of albumin, globulins and lipoproteins. The second equation predicts P(t:p) of drugs residing predominantly in the interstitial space of tissues. Therefore, the fractional volume content of interstitial space in each tissue replaced drug solubilities in the first equation. Following the development of these equations, regression analyses between P(t:p) of muscle and those of the other tissues were examined. The average ratio of predicted-to-experimental P(t:p) values was 1.26 (SD = 1.40, r = 0.90, n = 269), and 85% of the 269 predicted values were within a factor of three of the corresponding literature values obtained under in vivo and in vitro conditions. For predicted and experimental P(t:p), linear relationships (r > 0.9 in most cases) were observed between muscle and other tissues, suggesting that P(t:p) of muscle is a good predictor for the P(t:p) of other tissues. The two previous equations could explain the mechanistic basis of these linear relationships. The practical aim of this study is a worthwhile goal for pharmacokinetic screening of new drug candidates.

Animals↗

Relative lipid content as the sole mechanistic determinant of the adipose tissue:blood partition coefficients of highly lipophilic organic chemicals.

The adipose tissue:blood partition coefficient (PCat:b) refers to the ratio of chemical concentration or solubility in adipose tissue and blood. The solubility of a chemical in adipose tissue or whole blood is equal to the sum total of its solubility in lipid and water fractions of these matrices. For highly lipophilic organic chemicals (HLOCs, i.e., chemicals with log n-octanol:water partition coefficients (PCo:w) greater than four), their solubility in the water fractions of both tissue and blood is negligible, and therefore their solubility in lipid fractions of tissue and blood alone determines PCat:b. Since the numerical value representing chemical solubility in lipids is likely to be the same for both blood lipids and adipose tissue lipids, the PCat:b values should be hypothetically, equal to the ratio of lipid content of adipose tissue and blood. The objective of the present study was therefore to verify whether the PCat:bs of HLOCs (volatile organics, dioxins, PCBs, PBBs, DDT) are equal to the ratio of adipose tissue and blood lipid levels. The data on lipid content of rat and human blood and adipose tissues were obtained from the literature. The calculated tissue:blood lipid ratios were comparable to the human and rat PCat:b of volatile organic chemicals, dioxins, PCBs, PBBs and/or DDT obtained from the literature. These results then suggest that, regardless of the identity and PCo:w of HLOCs, their PCat:b is equal to the ratio of lipid in adipose tissues and blood.

Adipose Tissue↗

Searching the schizophrenic brain for temporal lobe deficits: a systematic review and meta-analysis.

BACKGROUND: Several empirical studies have found temporal lobe impairments in many patients with schizophrenia. The strength and consistency of this evidence, however, has not been evaluated and synthesized quantitatively. Hence, we ask to what extent are temporal cortices really defective in schizophrenia? METHODS: Meta-analytical methods were used to determine the magnitude of evidence in support of structural and physiological temporal-hippocampal system deficits in schizophrenia. We report effect sizes from studies since 1980 that used structural (CT, MRI) and functional (SPECT, PET) neuroimaging methods. RESULTS: Both structural and functional imaging literatures are distinguished by heterogeneity whereby most patients show normative temporal function and structure, a minority shows diminished values and some patients demonstrate augmented function and structure rather than a deficit. CONCLUSIONS: The findings are hard to incorporate within single disease models that propose major involvement of the temporal system in schizophrenia, at least at the degree of resolution obtained with current imaging technology.

Humans↗