Determination of the effect of lipophilicity on the in vitro permeability and tissue reservoir characteristics of topically applied solutes in human skin layers

In order to establish the relationship between solute lipophilicity and skin penetration (including flux and concentration behavior), we examined the in vitro penetration and membrane concentration of a series of homologous alcohols (C2-C10) applied topically in aqueous solutions to human epidermal, full-thickness, and dermal membranes. The partitioning/distribution of each alcohol between the donor solution, stratum corneum, viable epidermis, dermis, and receptor phase compartments was determined during the penetration process and separately to isolated samples of each tissue type. Maximum flux and permeability coefficients are compared for each membrane and estimates of alcohol diffusivity are made based on flux/concentration data and also the related tissue resistance (the reciprocal of permeability coefficient) for each membrane type. The permeability coefficient increased with increasing lipophilicity to alcohol C8 (octanol) with no further increase for C10 (decanol). Log vehicle:stratum corneum partition coefficients were related to logP , and the concentration of alcohols in each of the tissue layers appeared to increase with lipophilicity. No difference was measured in the diffusivity of smaller more polar alcohols in the three membranes; however, the larger more lipophilic solutes showed slower diffusivity values. The study showed that the dermis may be a much more lipophilic environment than originally believed and that distribution of smaller nonionized solutes into local tissues below a site of topical application may be estimated based on knowledge of their lipophilicity alone.

Ultrasonic absorption in polymer gel dosimeters

Ultrasonic absorption in polymer gel dosimeters was investigated. An ultrasonic interferometer was used to study the frequency (f) dependence of the absorption coefficient (alpha) in a polyacrylamide gel dosimeter (PAG) in the frequency range 5-20 MHz. The frequency dependence of ultrasonic absorption deviated from that of an ideal viscous fluid. The presence of relaxation mechanisms was evidenced by the frequency dependence of alpha/f(2) and the dispersion in ultrasonic velocity. It was concluded that absorption in polymer gel dosimeters is due to a number of relaxation processes which may include polymer-solvent interactions as well as relaxation due to motion of polymer side groups. The dependence of ultrasonic absorption on absorbed dose and formulation was also investigated in polymer gel dosimeters as a function of pH and chemical composition. Changes in dosimeter pH and chemical composition resulted in a variation in ultrasonic dose response curves. The observed dependence on pH was considered to be due to pH induced modifications in the radiation yield while changes in chemical composition resulted in differences in polymerisation kinetics. (C) 2003 Elsevier B.V. All rights reserved.

Effect of solute lipophilicity on penetration through canine skin

Objective To investigate the effect of lipophilicity on the percutaneous penetration of a homologous series of alcohols through canine skin Design Skin harvested from Greyhound thorax was placed in Franz-type diffusion cells and the in vitro passage of radio-labelled (C-14) alcohols (ethanol, butanol, hexanol and octanol (Log P 0.19 - 3.0)) through separate skin sections was measured in replicates of five. Permeability coefficient (k(P), cm/h), maximum flux (J(max), mol/cm(2)/h) and residue remaining within the skin were determined. Results The k(P) increased with increasing lipophilicity (6.2 x 10(-4) +/- 1.6 x 10(-4) cm/h for ethanol to 1.8 x 10(-2) 3.6 x 10(-3) cm/h for octanol). Alcohol residues remaining within each skin sample followed a similar pattern. An exponential decrease in Jmax with increasing lipophilicity was observed. Conclusion Changes in canine skin permeability occur with increasing alcohol lipophilicity. This finding has practical consequences for the design of topical formulations and optimisation of drug delivery through animal skin.

Effect of vehicle pretreatment on the flux, retention, and diffusion of topically applied penetrants in vitro

Purpose. The flux of a topically applied drug depends on the activity in the skin and the interaction between the vehicle and skin. Permeation of vehicle into the skin can alter the activity of drug and the properties of the skin barrier. The aim of this in vitro study was to separate and quantify these effects. Methods. The flux of four radiolabeled permeants (water, phenol, diflunisal, and diazepam) with log K-oct/water values from 1.4 to 4.3 was measured over 4 h through heat-separated human epidermis pretreated for 30 min with vehicles having Hildebrand solubility parameters from 7.9 to 23.4 (cal/cm(3))(1/2). Results. Enhancement was greatest after pretreatment with the more lipophilic vehicles. A synergistic enhancement was observed using binary mixtures. The flux of diazepam was not enhanced to the same extent as the other permeants, possibly because its partitioning into the epidermis is close to optimal (log K-oct 2.96). Conclusion. An analysis of the permeant remaining in the epidermis revealed that the enhancement can be the result of either increased partitioning of permeant into the epidermis or an increasing diffusivity of permeants through the epidermis.

Characterisation of grafted supports used for solid-phase synthesis

A series of 'pellicular' type supports were fabricated by direct gamma-radiation-mediated graft polymerisation of styrene onto polypropylene, followed by aminomethylation. Raman spectroscopy was used for measuring the level of penetration of polystyrene graft into polypropylene, and other structural features such as density of graft and depth of functionalisation. The kinetics of the coupling of fluorenylmethylcarbamate (Fmoc)-labelled amino acids, to the aminomethylated polystyrene grafts have been measured by UV absorption followed cleavage of the Fmoc chromophore. The Raman spectroscopy results showed that for this series of experiments the calculated rate coefficient for coupling of Fmoc-labelled amino acids was primarily dependent on graft thickness, but was also influenced by the proportion of polystyrene graft to polypropylene. In general, it was also shown that with increasing loading capacity of support the calculated rate coefficient for amino-acid coupling decreased correspondingly. In addition, a support that had both a high rate coefficient and a high loading capacity was prepared from polypropylene base material with a co-continuous porous structure (high surface area). (C) 2003 Society of Chemical Industry.

Reliability of scores between stroke patients and significant others on the Reintegration to Normal Living (RNL) Index

Purpose: This study measured reliability between stroke patients' and significant others' scores on items on the Reintegration to Normal Living (RNL) Index and whether there were any scoring biases. Method The 11-item RNL Index was administered to 57 pairs of patients and significants six months after stroke rehabilitation. The index was scored using a 10-point visual analogue scale. Patient and significant other demographic information and data on patients' clinical, functional and cognitive status were collected. Reliability was measured using the intra-class correlation coefficient (ICC) and percent agreement. Results: Overall poor reliability was found for the RNL Index total score (ICC=.36, 95% CI. 07 to .59) and the daily functioning subscale (ICC=.24, 95% CI -.003 to .46) and moderate reliability was found for the perception of self subscale (ICC=.55, 95 % CI .28 to .73). There was a moderate bias for patients to rate themselves as achieving better reintegration than was indicated by significant others, although no demographic or clinical factors were associated with this bias. Exact match agreement was best for the subjective items and worse for items reflecting mobility around the community and participation in a work activity. Conclusions: Caution is needed when interpreting patient information reported by significant others on the RNL Index. The use of a shorter scale to rate the RNL Index requires investigation.

Reproducibility of a laboratory-based 40-km cycle time-trial on a stationary wind-trainer in highly trained cyclists

The purpose of the present study was to examine the reproducibility of laboratory-based 40-km cycle time-trial performance on a stationary wind-trainer. Each week, for three consecutive weeks, and on different days, forty-three highly trained male cyclists ((x) over bar +/- SD; age = 25 +/- 6 y; mass = 75 +/- 7 kg; peak oxygen uptake [(V) over dot O-2 peak] = 64.8 +/- 5.2 ml x kg(-1) x min(-1)) performed: 1) a (V) over dot O-2 peak test, and 2) a 40-km time-trial on their own racing bicycle mounted to a stationary wind-trainer (Cateye - Cyclosimulator). Data from all tests were compared using a one-way analysis of variance. Performance on the second and third 40-km time-trials were highly related (r = 0.96; p < 0.001), not significantly different (57:21 +/- 2:57 vs. 57:12 +/- 3:14 min:s), and displayed a low coefficient of variation (CV) = 0.9 +/- 0.7%. Although the first 40-km time-trial (58:43 +/- 3:17min:s) was not significantly different from the second and third tests (p = 0.06), inclusion of the first test in the assessment of reliability increased within-subject CV to 3.0 +/- 2.9%. 40-km time-trial speed (km x h(-1)) was significantly (p < 0.001) related to peak power output (W; r = 0.75), (V) over dot O-2 peak (1 x min(-1); r = 0.53), and the second ventilatory turnpoint (1 x min(-1); r = 0.68) measured during the progressive exercise tests. These data demonstrate that the assessment of 40-km cycle time-trial performance in well-trained endurance cyclists on a stationary wind-trainer is reproducible, provided the athletes perform a familiarization trial.

Reliability of electromyographic and torque measures during isometric axial rotation exertions of the trunk

Objective: The aim of the present study was to investigate the between-days reliability of electromyographic (EMG) measurement of 6 bilateral trunk muscles and also the torque output in 3 planes during isometric right and left axial rotation at different exertion levels. Methods: Ten healthy subjects performed isometric right and left axial rotation at 100, 70, 50 and 30% maximum voluntary contractions in two testing sessions at least 7 days apart. EMG amplitude and frequency analyses of the recorded surface EMG signals were performed for rectus abdominis, external oblique, internal oblique, latissimus dorsi, iliocostalis lumborum and multifidus bilaterally. The primary torque in the transverse plane and the coupling torques in sagittal and coronal planes were measured. Results: For both EMG amplitude and frequency values, good (intraclass correlation coefficient, ICC = 0.75-0.89) to excellent (ICC greater than or equal to 0.90) reliability was found in the 6 trunk muscles at different exertion levels during axial rotation. The reliability of both maximal isometric axial rotation torque and coupling torques in sagittal and coronal planes were found to be excellent (ICC greater than or equal to 0.93). Conclusions: Good to excellent reliability of EMG measures of trunk muscles and torque measurements during isometric axial rotation was demonstrated. This provides further confidence of using EMG and triaxial torque assessment as outcome measures in rehabilitation and in the evaluation of the human performance in the work place. (C) 2003 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Unexpected clobetasol propionate profile in human stratum corneum after topical application in vitro

Purpose. The validity of using drug amount-depth profiles in stratum corneum to predict uptake of clobetasol propionate into stratum corneum and its transport into deeper skin layers was investigated. Methods. In vitro diffusion experiments through human epidermis were carried out using Franz-type glass diffusion cells. A saturated solution of clobetasol propionate in 20% (V/V) aqueous propylene glycol was topically applied for 48 h. Steady state flux was calculated from the cumulative amount of drug permeated vs. time profile. Epidermal partitioning was conducted by applying a saturated drug solution to both sides of the epidermis and allowing time to equilibrate. The tape stripping technique was used to define drug concentration-depth profiles in stratum corneum for both the diffusion and equilibrium experiments. Results. The concentration-depth profile of clobetasol propionate in stratum corneum for the diffusion experiment is biphasic. A logarithmic decline of the drug concentration over the first four to five tape strips flattens to a relatively constant low concentration level in deeper layers. The drug concentration-depth profile for the equilibrium studies displays a similar shape. Conclusions. The shape of the concentration-depth profile of clobetasol propionate is mainly because of the variable partitioning coefficient in different stratum corneum layers.

Reliability of moderate-intensity and vigorous physical activity stage of change measures for young adults

Background. The purpose of this study was to examine the reliability of stage of change (SOC) measures for moderate-intensity and vigorous physical activity in two separate samples of young adults. Staging measures have focused on vigorous exercise, but current public health guidelines emphasize moderate-intensity activity. Method. For college students in the USA (n = 105) and in Australia (n = 123), SOC was assessed separately on two occasions for moderate-intensity activity and for vigorous activity. Test-retest repeatability was determined, using Cohen's kappa coefficient. Results. In both samples, the reliability scores for the moderate-intensity physical activity staging measure were lower than the scores for the vigorous exercise staging measure. Weighted kappa values for the moderate-intensity staging measure were in the fair to good range for both studies (0.50 and 0.45); for the vigorous staging measure kappa values were excellent and fair to good (0.76 and 0.72). Conclusions. There is a need to standardize and improve methods for staging moderate-intensity activity, given that such measures are used in public health interventions targeting HEPA (health-enhancing physical activity). (C) 2003 American Health Foundation and Elsevier Science (USA). All rights reserved.

Poor correlation of mid-femoral measurements by CT and hip measurements by DXA in the elderly

Background and aims: Hip fracture is a devastating event in terms of outcome in the elderly, and the best predictor of hip fracture risk is hip bone density, usually measured by dual X-ray absorptiometry (DXA). However, bone density can also be ascertained from computerized tomography (CT) scans, and mid-thigh scans are frequently employed to assess the muscle and fat composition of the lower limb. Therefore, we examined if it was possible to predict hip bone density using mid-femoral bone density. Methods: Subjects were 803 ambulatory white and black women and men, aged 70-79 years, participating in the Health, Aging and Body Composition (Health ABC) Study. Bone mineral content (BMC, g) and volumetric bone mineral density (vBMD, mg/cm(3)) of the mid-femur were obtained by CT, whereas BMC and areal bone mineral density (aBMD, g/cm(2)) of the hip (femoral neck and trochanter) were derived from DXA. Results: In regression analyses stratified by race and sex, the coefficient of determination was low with mid-femoral BMC, explaining 6-27% of the variance in hip BMC, with a standard error of estimate (SEE) ranging from 16 to 22% of the mean. For mid-femur vBMD, the variance explained in hip aBMD was 2-17% with a SEE ranging from 15 to 18%. Adjusting aBMD to approximate volumetric density did not improve the relationships. In addition, the utility of fracture prediction was examined. Forty-eight subjects had one or more fractures (various sites) during a mean follow-up of 4.07 years. In logistic regression analysis, there was no association between mid-femoral vBMD and fracture (all fractures), whereas a 1 SD increase in hip BMD was associated with reduced odds for fracture of similar to60%. Conclusions: These results do not support the use of CT-derived mid-femoral vBMD or BMC to predict DXA-measured hip bone mineral status, irrespective of race or sex in older adults. Further, in contrast to femoral neck and trochanter BMD, mid-femur vBMD was not able to predict fracture (all fractures). (C) 2003, Editrice Kurtis.

Simultaneous FT-NIR and ESR analyses to yield propagation rate coefficients for polymerization of methyl methacrylate based monomers

A hyphenated instrumental approach has been used to obtain reliable values for the propagation rate coefficients as a function of conversion for polymerizations of methyl methacrylate (MMA) and a mixture of MMA and ethyleneglycol dimethacrylate (EGDMA) with a 1:1 concentration of double bonds, from near the onset of the Trommsdorf region into the glass region. ESR spectroscopy was used to measure the radical concentration while FT-NIR fibre-optic spectroscopy was employed to measure instantaneously the double-bond concentration within the temperature-controlled cavity of the ESR instrument during polymerization. The advantage of this approach to the measurement of the rate coefficient is that it is equally applicable to branching and linear polymerizations. For the polymerization of methyl methacrylate, the values of the rate coefficient at the lowest conversions at which reliable values could be obtained were in agreement with recently reported values obtained by the PLP-SEC method. For the lowest conversions, the values obtained were 403 1 mol(-1) s(-1) at 306 K for MMA and 5201 mol(-1) s(-1) at 310 K for a 1:1 mixture of MMA and EGDMA. (C) 2003 Society of Chemical Industry.

Influence of shapes of selected vegetable materials on drying kinetics during fluidized bed drying

Three different particular geometrical shapes of parallelepiped, cylinder and sphere were taken from cut green beans (length:diameter = 1:1, 2:1 and 3:1) and potatoes (aspect ratio = 1:1, 2:1 and 3:1) and peas, respectively. Their drying behaviour in a fluidised bed was studied at three different drying temperatures of 30, 40 and 50 degreesC (RH = 15%). Drying curves were constructed using non-dimensional moisture ratio (MR) and time and their behaviour was modelled using exponential (MR = exp(-kt)) and Page (MR = exp(-kt(n))) models. The effective diffusion coefficient of moisture transfer was determined by Fickian method using uni- and three-dimensional moisture movements. The diffusion coefficient was least affected by the size when the moisture movement was considered three-dimensional, whereas the drying temperature had a significative effect on diffusivity as expected. The drying constant and diffusivity coefficients were on the descending order for potato, beans and peas. The Arrhenius activation energy for the peas was also highest, indicating a strong barrier to moisture movement in peas as compared to beans and skinless cut potato pieces. (C) 2003 Elsevier Science Ltd. All rights reserved.

Wall mediated transport in confined spaces: Exact theory for low density

We present a theory for the transport of molecules adsorbed in slit and cylindrical nanopores at low density, considering the axial momentum gain of molecules oscillating between diffuse wall reflections. Good agreement with molecular dynamics simulations is obtained over a wide range of pore sizes, including the regime of single-file diffusion where fluid-fluid interactions are shown to have a negligible effect on the collective transport coefficient. We show that dispersive fluid-wall interactions considerably attenuate transport compared to classical hard sphere theory.

Molecular transport in nanopores

Simulation of the transport of methane in cylindrical silica mesopores have been performed using equilibrium and nonequilibrium molecular dynamics (NEMD) as well as dual control volume grand canonical molecular dynamics methods. It is demonstrated that all three techniques yield the same transport coefficient even in the presence of viscous flow. A modified locally averaged density model for viscous flow, combined with consideration of wall slip through a frictional condition, gives a convincing interpretation of the variation of the transport coefficient over a wide range of densities, and for various pore sizes and temperatures. Wall friction coefficients extracted from NEMD simulations are found to be consistent with momentum transfer arguments, and the approach is shown to be more meaningful than the classical slip length concept. (C) 2003 American Institute of Physics.