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  • 1
    Electronic Resource
    Electronic Resource
    Microbial structural diversity estimated by dilution–extinction of phenotypic traits and T-RFLP analysis along a land-use intensification gradient (2004)
    Oxford, UK : Blackwell Publishing Ltd
    FEMS microbiology ecology 49 (2004), S. 0 
    Details
    ISSN: 1574-6941
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology
    Notes: The present work tested whether the relationship between functional traits and inoculum density reflected structural diversity in bacterial communities from a land-use intensification gradient applying a mathematical model. Terminal restriction fragment length polymorphism (T-RFLP) analysis was also performed to provide an independent assessment of species richness. Successive 10-fold dilutions of a soil suspension were inoculated onto Biolog GN® microplates. Soil bacterial density was determined by total cell and plate counts. The relationship between phenotypic traits and inoculum density fit the model, allowing the estimation of maximal phenotypic potential (Rmax) and inoculum density (KI) at which Rmax will be half-reduced. Though Rmax decreased with time elapsed since clearing of native vegetation, KI remained high in two of the disturbed sites. The genetic pool of bacterial community did not experience a significant reduction, but the active fraction responding in the Biolog assay was adversely affected, suggesting a reduction in the functional potential.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1016/j.femsec.2004.03.012
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  • 2
    Electronic Resource
    Electronic Resource
    Distribution Kinetics of Diazepam, Lidocaine and Antipyrine in the Isolated Perfused Rat Hindlimb (1997)
    Springer
    Pharmaceutical research 14 (1997), S. 1640-1643 
    Details
    ISSN: 1573-904X
    Keywords: pharmacokinetics ; indicator dilution ; permeability ; dispersion ; model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1012198922671
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  • 3
    Electronic Resource
    Electronic Resource
    In Vitro and in Vivo Evaluation in Rabbits of a Controlled Release 5-fluorouracil Subconjunctival Implant Based on Poly(D,L-lactide-co-glycolide) (1996)
    Springer
    Pharmaceutical research 13 (1996), S. 1059-1064 
    Details
    ISSN: 1573-904X
    Keywords: 5-fluorouracil ; ocular ; implants ; poly(D,L-lactide-co-glycolide) ; subconjunctiva
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To design a controlled release 5-fluorouracil (5-FU) implant to provide prolonged antifibroblast concentrations of 5-FU in the sub-conjunctival tissues but low concentrations of 5-FU in other ocular tissues. Methods. Implants (5 mg; 2.5 mm diameter × 1.2 mm thickness) of 5-FU or 9:1, 8:2, 7:3 5-FU to polymer mass ratios were made by compression. Poly(D,L-lactide-co-glycolide) polymers with 50:50 and 75:25 lactide to glycolide ratios were used. In vitro release characteristics of four types of implants were studied: 5-FU alone (CT), 5-FU/ polymer matrices (MT), coated 5-FU/polymer matrices with a central hole drilled through the matrix and coating (CM1), and with a central hole in the coating (CM2). MT and CM1 (9:1 drug/polymer) were selected for subconjunctival implantation in rabbits. 14C-5-FU levels in various ocular tissues and retrieved pellets were monitored. Results. First-order release was observed from CT, MT and CM1 implants. Zero-order release profiles were observed from CM2 implants. Drug release was retarded by formulating 5-FU in a matrix comprising poly(D,L-lactide-co-glycolide) which in turn could be modified by the lactide/glycolide ratio of the polymer, the drug to polymer ratio, coating, and hole dimensions. First-order release kinetics were observed for MT and CM1 implants in the in vivo study in rabbits. A correlation between in vitro and in vivo release was established which allowed in vivo release to be predicted from in vitro release data. For CM1, therapeutic tissue concentrations of 35.2 µg/g (conjunctiva) and 17.7µLg/g (sclera) were found at the implantation site up to 200 hours post-implantation. Tracer levels were undetectable in other ocular tissues. Conclusions. The CM1 implant maintained steady antifibroblast levels in target tissues and minimized levels in nontarget tissues.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1016062825360
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  • 4
    Electronic Resource
    Electronic Resource
    Epidermal Iontophoresis: I. Development of the Ionic Mobility-Pore Model (1998)
    Springer
    Pharmaceutical research 15 (1998), S. 1569-1578 
    Details
    ISSN: 1573-904X
    Keywords: iontophoresis ; ionic mobility ; free volume model ; Debye layer ; pore
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. An integrated ionic mobility-pore model for epidermal iontophoresis is developed from theoretical considerations using both the free volume and pore restriction forms of the model for a range of solute radii (r j ) approaching the pore radii (r p ) as well as approximation of the pore restriction form for r j /r p 〈 0.4. In this model, we defined the determinants for iontophoresis as solute size (defined by MV, MW or radius), solute mobility, solute shape, solute charge, the Debye layer thickness, total current applied, solute concentration, fraction ionized, presence of extraneous ions (defined by solvent conductivity), epidermal permselectivity, partitioning rates to account for interaction of unionized and ionized lipophilic solutes with the wall of the pore and electroosmosis. Methods. The ionic mobility-pore model was developed from theoretical considerations to include each of the determinants of iontophoretic transport. The model was then used to reexamine iontophoretic flux conductivity and iontophoretic flux-fraction ionized literature data on the determinants of iontophoretic flux. Results. The ionic mobility-pore model was found to be consistent with existing experimental data and determinants defining iontophoretic transport. However, the predicted effects of solute size on iontophoresis are more consistent with the pore-restriction than free volume form of the model. A reanalysis of iontophoretic flux-conductivity data confirmed the model's prediction that, in the absence of significant electroosmosis, the reciprocal of flux is linearly related to either donor or receptor solution conductivity. Significant interaction with the pore walls, as described by the model, accounted for the reported pH dependence of the iontophoretic transport for a range of ionizable solutes. Conclusions. The ionic mobility-pore iontophoretic model developed enables a range of determinants of iontophoresis to be described in a single unifying equation which recognises a range of determinants of iontophoretic flux.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1011907201096
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  • 5
    Electronic Resource
    Electronic Resource
    An Isolated In-Situ Rat Head Perfusion Model for Pharmacokinetic Studies (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 127-134 
    Details
    ISSN: 1573-904X
    Keywords: in-situ head perfusion ; pharmacokinetics ; red blood cells ; water
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To develop a viable, single pass rat head perfusion modeluseful for pharmacokinetic studies. Methods. A viable rat head preparation, perfused with MOPS-bufferedRinger's solution, was developed. Radiolabelled markers (red bloodcells, water and sucrose) were injected in a bolus into the internalcarotid artery and collected from the posterior facial vein over 28minutes. The double inverse Gaussian function was used to estimatethe statistical moments of the markers. Results. The viability of the perfusion was up to one hour, with optimalperfusate being 2% bovine serum albumin at 37°C, pH 7.4. Thedistribution volumes for red blood cells, sucrose and water (from all studies,n = 18) were 1.0 ± 0.3ml, 6.4 ± 4.2ml and 18.3 ± 11.9ml, respectively.A high normalised variance for red blood cells (3.1 ± 2.0) suggestsa marked vascular heterogeneity. A higher normalised variance forwater (6.4 ± 3.3) is consistent with additional diffusive/permeabilitylimitations. Conclusions. Analysis of the physiological parameters derived fromthe moments suggested that the kinetics of the markers were consistentwith distribution throughout the head (weight 25g) rather than justthe brain (weight 2g). This model should assist in studying solutepharmacokinetics in the head.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007500910566
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  • 6
    Electronic Resource
    Electronic Resource
    Lateral lontophoretic Solute Transport in Skin (1999)
    Springer
    Pharmaceutical research 16 (1999), S. 46-54 
    Details
    ISSN: 1573-904X
    Keywords: iontophoresis ; epidermis ; dermis ; clearance ; lateral transport ; velocity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The lateral iontophoretic transport of three solutes (sodium, ethanolamine, lidocaine) from an active electrode through skin and other tissues to an indifferent electrodes was investigated. Methods. Anodal epidermal iontophoresis was carried out on an in vivo rat model using constant direct current of 0.38 mA/cm2. Cells were fixed on the epidermis of anesthetized rats at distances of adjacent, 3 cm and 7 cm apart. After iontophoresis, tissues were dissected at 1 cm intervals between the electrodes. Concentrations of the radiolabelled solutes in tissues were determined by liquid scintillation counting or gamma counting. Results. The concentration of each solutes in the epidermis, dermis and other tissues was found to decrease in an exponential manner with lateral distance from the active electrode to the indifferent electrode. The detectable lateral distance for ethanolamine and lidocaine was less than 2 cm from the donor sites, at which distance the concentrations were not significantly different to those found in the corresponding contralateral site. The lateral drift velocities for all solutes in the epidermis and dermis were consistent with diffusivities of the order of 10-6 cm2/s. The drift velocity of sodium was greater than either lidocaine or ethanolamine. Conclusions. The decline in solute concentration with lateral distance is mainly due to clearance from the site of application by the skin's microcirculation and decreases with distance from the active electrode until a baseline concentration, similar to the contralateral tissue concentration is reached.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1018862510646
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  • 7
    Electronic Resource
    Electronic Resource
    In Vitro Human Epidermal and Polyethylene Membrane Penetration and Retention of the Sunscreen Benzophenone-3 from a Range of Solvents (1998)
    Springer
    Pharmaceutical research 15 (1998), S. 1863-1868 
    Details
    ISSN: 1573-904X
    Keywords: benzophenone-3 ; sunscreen ; penetration ; retention ; vehicle ; human epidermis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To study epidermal and polyethylene membrane penetration and retention of the sunscreen benzophenone-3 (BP) from a range of single solvent vehicles and evaluate solvent effects on permeability parameters. Methods. The solubility of BP was measured in a number of solvents. Penetration of BP across human epidermis and high density polyethylene (HDPE) membranes was studied from 50% saturated solutions in each solvent. Results. Maximal BP fluxes from the solvents across the two membranes varied widely. Highest fluxes were observed from 90% ethanol (EtOH) for epidermis and from isopropyl myristate (IPM) and C12−15 benzoate alcohols (C12−15 BA) for HDPE membrane. Both the flux and estimated permeability coefficient and skin-vehicle partitioning of BP appeared to be related to the vehicle solubility parameter (δv). The major effects of solvents on BP flux appear to be via changes in BP diffusivity through the membranes. Conclusions. Minimal penetration of sunscreens such as BP is best achieved by choosing vehicles with a δv substantially different to the solubility parameter of the membrane.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1011958006973
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  • 8
    Electronic Resource
    Electronic Resource
    Epidermal Iontophoresis: II. Application of the Ionic Mobility-Pore Model to the Transport of Local Anesthetics (1998)
    Springer
    Pharmaceutical research 15 (1998), S. 1579-1588 
    Details
    ISSN: 1573-904X
    Keywords: iontophoresis ; local anesthetics ; ionic mobility ; pore ; model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. An in vitro study was carried out to determine the iontophoretic permeability of local anesthetics through human epidermis. The relationship between physicochemical structure and the permeability of these solutes was then examined using an ionic mobility-pore model developed to define quantitative relationships. Methods. The iontophoretic permeability of both ester-type anesthetics (procaine, butacaine, tetracaine) and amide-type anesthetics (prilocaine, mepivacaine, lidocaine, bupivacaine, etidocaine, cinchocaine) were determined through excised human epidermis over 2 hrs using a constant d.c. current and Ag/AgCl electrodes. Individual ion mobilities were determined from conductivity measurements in aqueous solutions. Multiple stepwise regression was applied to interrelate the iontophoretic permeability of the solutes with their physical properties to examine the appropriateness of the ionic mobility-pore model and to determine the best predictor of iontophoretic permeability of the local anesthetics. Results. The logarithm of the iontophoretic permeability coefficient (log PC j , iont ) for local anesthetics was directly related to the log ionic mobility and MW for the free volume form of the model when other conditions are held constant. Multiple linear regressions confirmed that log PC j , iont was best defined by ionic mobility (and its determinants: conductivity, pKa and MW) and MW. Conclusions. Our results suggest that of the properties studied, the best predictors of iontophoretic transport of local anesthetics are ionic mobility (or pKa) and molecular size. These predictions are consistent with the ionic mobility pore model determined by the mobility of ions in the aqueous solution, the total current, epidermal permselectivity and other factors as defined by the model.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1011959217935
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  • 9
    Electronic Resource
    Electronic Resource
    Self Promotion of Deep Tissue Penetration and Distribution of Methylsalicylate After Topical Application (1999)
    Springer
    Pharmaceutical research 16 (1999), S. 427-433 
    Details
    ISSN: 1573-904X
    Keywords: rats ; percutaneous ; salicylates ; metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To determine how changes in cutaneous blood flow induced in-vivo by methylsalicylate (MeSA), compared to non-rubefacient trie-thanolamine salicylate (TSA), affected topical salicylate absorption and distribution, and to assess formulation therapeutic potential by comparing tissue concentrations to published antiinflammatory concentrations. Methods. Flux of salicylate from MeS A and TSA formulations applied to full-thickness rat skin was determined using in vitro diffusion cells. Anaesthetised rats were then used to quantify salicylate concentrations in plasma and tissues underlying the application site for the two formulations over a 6h period. In vitro and in vivo absorption profiles were then compared and the effect of MeSA on cutaneous blood flow assessed. Results. In vitro flux of salicylate from the MeSA formulation was 40% higher, though after correcting for differences in formulation concentrations the ratio of permeability coefficients was reversed. Contrary to the in vitro predictions, in vivo tissue and plasma concentrations of salicylate in rats rose rapidly in the first 1 hr and were more than the predicted 1.4-fold higher for MeSA. This effect was mirrored by the increase in blood flow induced by MeSA in human cutaneous vessels and that reported in the literature. Potential therapeutic levels were not seen below superficial muscle layers. Conclusions. Direct tissue penetration of salicylate occurs below application sites from both MeSA and TSA formulations. Tissue concentrations of MeSA were higher than predicted due to its rapid distribution in the blood.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1018834021066
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  • 10
    Electronic Resource
    Electronic Resource
    On the validity of the dispersion model of hepatic drug elimination when intravascular transit time densities are long-tailed (1997)
    Springer
    Bulletin of mathematical biology 59 (1997), S. 911-929 
    Details
    ISSN: 1522-9602
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Mathematics
    Notes: Abstract The dispersion model with mixed boundary conditions uses a single parameter, the dispersion number, to describe the hepatic elimination of xenobiotics and endogenous substances. An implicita priori assumption of the model is that the transit time density of intravascular indicators is approximated by an inverse Gaussian distribution. This approximation is limited in that the model poorly describes the tail part of the hepatic outflow curves of vasclar indicators. A sum of two inverse Gaussian functions is proposed as an alternative, more flexible empirical model for transit time densities of vascular references. This model suggests that a more accurate description of the tail portion of vascular reference curves yields an elimination rate constant (or intrinsic clearance) which is 40% less than predicted by the dispersion model with mixed boundary conditions. The results emphasize the need to accurately describe outflow curves in using them as a basis for determining pharmacokinetic parameters using hepatic elimination models.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02459999
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