Apparent Penetration Research Articles

Estimation of relative permittivity for measuring soil texture-dependent water content by GNSS-IR

Techniques for measuring the soil moisture content (SMC) using global navigation satellite system-interferometric reflectometry (GNSS-IR) with a positioning antenna have been reported. However, conventional methods are limited to evaluating the relative change in volumetric water content in a dry range for certain soil textures. In this study, we proposed a method to measure relative permittivity using GNSS-IR and evaluated its applicability at two sites with different soil textures and moisture content. The true multipath penetration depth was obtained from the tangent dielectric suitable for the soil textures, and the apparent penetration depth affected by the relative permittivity of the soil was calculated from the signal-to-noise ratio measured by GNSS. The relative permittivity of the soil was obtained from the ratio of these values and compared with the relative permittivity of the SMC sensor. As a result, we could measure soil permittivity according to soil textures from dry to wet conditions from GNSS-IR, except when the true multipath wave penetration depth was less than 1.5 cm, at which only surface reflection occurred. Sandy soils with a low dielectric loss tangent and wet areas with small changes in the depth of penetration of electromagnetic waves are particularly suitable environments for this method.

ULTRASTRUCTURAL ASPECTS OF TWO MORPHOTYPES OF GRAM-NEGATIVE BACTERIA LOCATED IN THE ENDOMYSIUM OF THE SKELETAL MUSCLE OF Trachurus trecae (CARANGIDAE) IN ANGOLA

Ultrastructural and histopathological ocasional parasite survey of some samples of the teleostean, Trachurus trecae (Carangidae), collected on the Atlantic coast of Angola were found infected by prokaryotic organisms identified as belonging to two morphotypes of Gram-negative bacteria located inside on extracellular space of the connective tissue of the endomysium among the skeletal muscle fibers. By serial ultrathin sections was observed that the majority of bacteria were cylindrical morphology, some appeared in division measuring 2.8 ± 0.7 µm long x 0.9 ± 0.3 µm in diameter, other having spherical form measuring 2.8 ± 0.4 µm in diameter. The ultrastructural organization of the myofibres contacting with of region where the bacteria were located, present the myofibrils ultrastructurally disorganized, without the typical muscular striations. The pathogenic effects of the two bacterial association seemed to give rise to the myofibrils lysis and concomitant disintegration and rupture of the wall of the muscle fibres, forming a recess where the bacteria live in close proximity. Muscle fiber wall in contact with the local where the bacteria were localized appeared lysed, disorganized and without the typical striations where, among them, some bacteria were observed. Some aspects of apparent penetration of bacteria through the degraded wall of the myofibers into the interior of the fibers, were observed and discussed. This is the first description of the pathogenic activity of bacteria in muscle tissue of a teleost from the aquatic fauna of Angola.

Evidence for the Heterogeneity of the Pore Structure of Rocks from Comparing the Results of Various Techniques for Measuring Hydraulic Properties

We applied three oscillatory methods, the previously presented axial pore-pressure and pore-flow methods, and the laboratory application of the radial oscillatory pore-flow method, and performed steady-state flow-through experiments (Darcy tests), for comparison, in experiments on samples of Westerly granite and Wilkeson sandstone. The granite and the sandstone exhibit pore spaces dominated by micro-fractures and by the granular-medium character with a connected porosity of about 1 and 10 %, respectively. Permeability determined by the axial pore-pressure method shows the closest agreement with the results of the Darcy tests. Apparent porosity and drained modulus derived from specific storage capacity deviate from measured connected porosity and reference values, respectively. The observed deviations of the hydraulic properties between methods suggest that they bear information about the structure of the pore space. Only for the sandstone, anisotropy in hydraulic properties appears to contribute to differences between the results of the various methods. We argue that oscillatory testing provides three indicators for heterogeneity, period dependence, the relation between apparent and connected porosity, and the relation between amplitude ratio and apparent penetration depth, calculated from the simple scaling law for homogeneous materials. These indicators consistently classify the samples of Wilkeson sandstone as hydraulically homogeneous and those of Westerly granite as heterogeneous.

Heat Stress and Pulsed Unfocused Ultrasound: The Viability of these Physical Approaches for Drug Delivery into Testicular Seminiferous Tubules.

To investigate the application of Scrotal Heat Stress (SHS) and Pulsed Unfocused Ultrasound (PuFUS) to explore Blood-Testis Barrier (BTB) permeability in adult mice. The BTB provides a stable microenvironment and a unique immune barrier for spermatogenesis. Meanwhile, it blocks macromolecular substances access, including therapeutic agents and antibodies, thereby it decreases the therapeutic or immunocontraception effects. To determine the viability of these physical approaches in delivering macromolecular substances into seminiferous tubules. Mice were subjected to receive single SHS intervention at 39°C, 41°C, or 43°C for 30 min. Whereas, mice received the PuFUS intervention at 1.75w/cm2, 1.25w/cm2, and 2.5w/cm2 for 2 min, 5 min, and 10 min, respectively. The Biotin and macromolecular substances (IgG, IgM, and exosomes) were separately injected into the testicular interstitium at different times following SHS or PuFUS interventions, to observe their penetration through BTB into seminiferous tubules. As detected by Biotin tracer, the BTB opening started from day-2 following the SHS and lasted for more than three days, whereas the BTB opening started from 1.5h following PuFUS and lasted up to 24h. Apparent penetration of IgG, IgM, and exosomes into seminiferous tubules was observed after five days of the SHS at 43°C, but none at 39°C, or any conditions tested with PuFUS. The current results indicate that SHS at 43°C comparatively has the potential for delivering macromolecular substances into seminiferous tubules, whereas the PuFUS could be a novel, quick, and mild approach to open the BTB. These strategies might be useful for targeted drug delivery into testicular seminiferous tubules. However, further studies are warranted to validate our findings.

Penetration behavior of an ionic liquid in thin-layer silica coating: Ionic liquid deuteration and neutron reflectivity analysis

A quantitative analysis method for monitoring liquid penetration into nanosize thin layer samples was developed using neutron reflectivity (NR). In this study, we synthesized a partly deuterated ionic liquid (IL) and studied its penetration behavior in perhydropolysilazane-derived silica (PDS) thin layers using NR. The penetration depth of the deuterated IL was estimated to be 184 Å for the 24 h IL-submerged sample and 410 Å for the 72 h IL-submerged sample. In addition, using the obtained penetration depth, an apparent penetration rate constant (kapp) of 0.024 h−1 was evaluated. Thus liquid penetration behavior in PDS thin layer samples can be quantitatively discussed by evaluation of kapp using NR analysis.

Microscopic parameters from high-resolution specific heat measurements on superoptimally substitutedBaFe2(As1−xPx)2single crystals

We investigate the electronic specific heat of overdoped BaFe$_{2}$(As$_{1-x}$P$_{x}$)$_{2}$ single crystals in the superconducting state using high-resolution nanocalorimetry. From the measurements, we extract the doping dependence of the condensation energy, superconducting gap $\Delta$, and related microscopic parameters. We find that the anomalous scaling of the specific heat jump $\Delta C \propto T_{\mathrm{c}}^3$, found in many iron-based superconductors, in this system originates from a $T_\mathrm{c}$-dependent ratio $\Delta/k_\mathrm{B}T_\mathrm{c}$ in combination with a doping-dependent density of states $N(\varepsilon_\mathrm{F})$. A clear enhancement is seen in the effective mass $m^{*}$ as the composition approaches the value that has been associated with a quantum critical point at optimum doping. However, a simultaneous increase in the superconducting carrier concentration $n_\mathrm{s}$ maintains the superfluid density, yielding an apparent penetration depth $\lambda$ that decreases with increasing $T_\mathrm{c}$ without sharp divergence at the quantum critical point. Uemura scaling indicates that $T_\mathrm{c}$ is governed by the Fermi temperature $T_\mathrm{F}$ for this multi-band system.

Alternation of adriamycin penetration kinetics in MCF-7 cells from 2D to 3D culture based on P-gp expression through the Chk2/p53/NF-κB pathway

Monolayer cells are largely different from tumor masses, and might misguide drug screenings. 3D in vitro cell culture models simulate the characteristics of tumor masses in vivo and have recently been used in many studies of anti-cancer drugs. Among various 3D cell culture models, multi-cellular layer (MCL) models allow for the direct quantitative assessment of the penetration of chemotherapeutic agents through solid tissue environments without requiring the use of fluorescently labeled drugs or imaging molecules. Therefore, in our present study, a 3D-no base and embedded MCF-7 MCL model was successfully developed for a 14-day culture. Over time, its thickness and cell layers increased and exhibited highly proliferative properties and drug resistance to adriamycin (ADR) with markedly elevated IC50 values. Meanwhile, G2/M stage cycle arrest was also observed, which likely up-regulated P-gp expression through the Chk2/p53/NF-κB pathway. The elevated P-gp expression altered the ADR penetration kinetics in MCF-7 MCLs in vitro by accelerating the apparent penetration of ADR through the intercellular spaces of the MCLs. Additionally, a decreased ADR retention within tumor cells was observed, but could be significantly reversed by a P-gp inhibitor. The attenuated ADR retention in the deeper cells of tumor masses was confirmed in xenografted mice in vivo. This phenomenon could be elucidated by the mathematical modeling of penetration kinetics parameters. Our study provided a new model that evaluated and improved the quantification of the drug penetration kinetics, revealed the relationship between P-gp and drug penetration through tumor masses, and suggested the potential molecular mechanisms.

Infiltrative Recurrent Eccrine Spiradenoma of the Anterior Neck Treated Using Mohs Micrographic Surgery

Eccrine spiradenoma (ES) is a rare, usually benign adnexal tumour that may be sporadic or familial. The cell of origin has been debated and is thought to arise from the hair follicle.1 We describe a patient with Fitzpatrick skin type V who developed recurrent ES of the anterior neck treated using Mohs micrographic surgery (MMS). A 57-year-old woman with Fitzpatrick skin type V presented with a 5-month history of tender enlarging lesions on the anterior neck. She reported excision of a lesion at this site 14 years before. Examination revealed an 85-mm scar on the anterior neck. Firm tender subcutaneous papules and nodules were noted at two sites adjacent to the scar measuring 29 by 17 mm and 30 by 13 mm (Figure ​(Figure1).1). Skin biopsy showed a well-circumscribed tumor composed of small basaloid cells with interspersed vascular spaces and duct-like structures, typical of ES. Figure 1 Recurrent eccrine spiradenoma. Firm tender papules adjacent to scar from previous excision (central neck and left lateral neck sites). Ultrasound of the neck confirmed that the lesions were confined to the skin and subcutaneous tissue, with no apparent penetration of deep fascia and no lymphadenopathy. She underwent MMS of the two clinically apparent areas of recurrence. MMS histology confirmed tumor extension into the subcutaneous tissue (Figure ​(Figure2).2). At the left lateral neck site, tumor-negative MMS margins were achieved after four stages and eight blocks, with a defect size of 47 by 26 mm. At the central neck site, tumor-negative MMS margins were also achieved after four stages and eight blocks, with a defect size of 42 by 28 mm (Figure ​(Figure3).3). Both defects were repaired using primary direct closure. The intervening scar between the defects was also excised at closure. The histologic appearance of the debulked tissue from MMS at both sites confirmed appearances in keeping with ES, with cystic change noted at the left lateral site. No malignant changes were seen. Figure 2 (A) Photomicrograph of spiradenoma extending into fat, shown at ×10 magnification (hematoxylin and eosin staining). (B) The black rectangle, shown at ×40 magnification, illustrating the cellular morphology of spiradenoma. Figure 3 Final defects on anterior and left lateral neck. There was no evidence of recurrence 15 months after MMS.

GRL-04810 and GRL-05010, Difluoride-Containing Nonpeptidic HIV-1 Protease Inhibitors (PIs) That Inhibit the Replication of Multi-PI-Resistant HIV-1 In Vitro and Possess Favorable Lipophilicity That May Allow Blood-Brain Barrier Penetration

We designed, synthesized, and identified two novel nonpeptidic human immunodeficiency virus type 1 (HIV-1) protease inhibitors (PIs), GRL-04810 and GRL-05010, containing the structure-based designed privileged cyclic ether-derived nonpeptide P2 ligand, bis-tetrahydrofuranylurethane (bis-THF), and a difluoride moiety, both of which are active against the laboratory strain HIV-1LAI (50% effective concentrations [EC50s], 0.0008 and 0.003 μM, respectively) with minimal cytotoxicity (50% cytotoxic concentrations [CC50s], 17.5 and 37.0 μM, respectively, in CD4(+) MT-2 cells). The two compounds were active against multi-PI-resistant clinical HIV-1 variants isolated from patients who had no response to various antiviral regimens. GRL-04810 and GRL-05010 also blocked the infectivity and replication of each of the HIV-1NL4-3 variants selected by up to 5 μM lopinavir (EC50s, 0.03 and 0.03 μM, respectively) and atazanavir (EC50s, 0.02 and 0.04 μM, respectively). Moreover, they were active against darunavir (DRV)-resistant variants (EC50 in 0.03 to 0.034 μM range for GRL-04810 and 0.026 to 0.043 μM for GRL-05010), while DRV had EC50s between 0.02 and 0.174 μM. GRL-04810 had a favorable lipophilicity profile as determined with the partition (log P) and distribution (log D) coefficients of -0.14 and -0.29, respectively. The in vitro blood-brain barrier (BBB) permeability assay revealed that GRL-04810 and GRL-05010 may have a greater advantage in terms of crossing the BBB than the currently available PIs, with apparent penetration indexes of 47.8 × 10(-6) and 61.8 × 10(-6) cm/s, respectively. The present data demonstrate that GRL-04810 and GRL-05010 exert efficient activity against a wide spectrum of HIV-1 variants in vitro and suggest that two fluorine atoms added to their bis-THF moieties may well enhance their penetration across the BBB.

Effect of electromagnetic field on the slag resistance of MgO-C refractories

The recent years have witnessed an unprecedented growth in the development and deployment of electromagnetic field(EMF) used in steel metallurgy. This paper investigates the effect of EMF on the slag resistance of MgO-C refractories. Using MgO-C refractories containing 14% carbon and the slag with a basicity(CaO/SiO2) of around 0.8, the experiments of melting slag resistance of MgO-C refractories were carried out in an induction furnace and a resistance furnace. The results show that in induction furnace having EMF, the refractory sample corroded by the slag has an apparent penetration layer. MgFe2O4 phase is formed at a low temperature by MgO dissolved in Fe2O3. The low melting phases are monticellite (CaMgSiO4, CMS) and forsterite (Mg2SiO4, MS). Under the condition of resistance furnace without EMF, scaling MgO dissolves into slag and reacts with Al2O3 to generate MgAl2O4 phase. The low melting phases are gehlenite (Ca2Al2SiO7, C2A2S) and akermanite (Ca2MgSi2O, C2MS2). As EMF exists at a high temperature, it could enhance the diffusion and penetration of Fe2+/3+ ions to form the MgFe2O4 phase. At the same time, some MgAl2O4 spinels exist. However, only MgAl2O4 phase can be generated without EMF.

Determination of albumin sorption to intraocular lenses by radiolabeling and confocal laser scanning microscopy

To determine albumin adsorption profiles and penetration depth of 3 intraocular lens (IOL) materials over time using confocal laser scanning microscopy (CLSM) and radiolabeling. Centre for Contact Lens Research, School of Optometry, and Department of Biology, University of Waterloo, Waterloo, Ontario, Canada. Poly(methyl methacrylate) (PMMA), silicone, and foldable hydrophilic acrylic IOLs were incubated in 0.5 mg/mL bovine serum albumin (BSA) for 1, 7, and 14 days. The BSA was conjugated with lucifer yellow VS to allow identification of the protein location by fluorescent imaging with CLSM. Next, the protein uptake was quantified using 2% (125)I-labeled BSA. Confocal laser scanning microscopy showed increasing BSA uptake for silicone and PMMA IOLs after 14 days of incubation (P<.05), with an apparent penetration depth of 8.7 microm +/- 1.9 (SD) and 9.2 +/- 1.4 microm, respectively. For hydrophilic acrylic IOLs, BSA was detected at a depth of 38 +/- 7.4 microm after 1 day, followed by an increase to 192.7 +/- 16.2 microm after 14 days. Despite the penetration depth into the hydrophilic acrylic IOLs, quantitative results confirmed that PMMA and hydrophilic acrylic deposited significantly less BSA (mean 278.3 +/- 41.7 ng and 296.5 +/- 33.1 ng, respectively) than silicone IOLs (mean 392.6 +/- 37.6 ng) (P<.05). Silicone and PMMA IOL materials showed BSA sorption near the lens surface only, while BSA penetrated deep into the hydrophilic acrylic IOL matrix. Combining the qualitative CLSM method and quantitative radiolabeling technique provided detailed information on protein interactions with implantable biomaterials.

POSSIBILITIES OF CEMENT CONTENT REDUCTION IN CONCRETES WITH ADMIXTURE OF SUPERPLASTICISER SNF

The problem of the possibility of cement saving in concretes with admixture of sodium salt of formaldehydic polycondensates of sulphonic‐napthalene acids (SNF) is presented. Executed investigations show a strong plastifying performance of this admixture as well as an elongation of setting time of Portland cements. On adding 1,5 % of admixture it is possible to obtain a substantial saving of cement with simultaneous reduction of water amount (constant W/C ratio), without a change of consistency of concrete mixture apparent density, compressive strength, absorption and water penetration of concrete. For the estimation of economic effectiveness of superplasticiser SNF it is proposed to introduce an index of cement saving Sc and an index of cement utilisation in concretes Iec .

Skin Penetration by Metal Compounds with Special Reference to Copper

The process of diffusion into and across the different structures of the skin by chemicals is reviewed, with particular attention given to copper compounds. The scarce data available from the literature indicate that, in contact with the skin, metallic copper will oxidize, and the compounds resulting will penetrate it. Results from our lab confirm that copper compounds formed with skin exudates penetrate the human stratum corneum in a time-dependent fashion. The only quantitative diffusion rates for copper compounds given in the literature so far refer to experiments performed on the cat in vitro and in vivo. Transformation of data from that study, based on certain assumptions, lead to estimated Kp values of 10−6 to 10−5 cm/h for the copper salts tested, values that lie at the lower end of skin diffusivity rates measured for transition metal salts.Permeability coefficients for aqueous copper sulfate and acetate through human epidermis in vitro measured in our laboratory are of the order of 10−6 cm/h. For copper compounds formulated in combination with zinc compounds for therapeutic purposes, applied on dermatomed human skin in vitro in various vehicles, the apparent penetration coefficients Kp were in the range of 3.2 × 10−6 and 1.6 × 10−5 cm/h.

Pathogenicity of Phaeoacremonium aleophilum and Phaeomoniella chlamydospora on Grape Berries in California

Injured and non-injured grape berries were inoculated with spore suspension of Phaeomoniella chlamydospora or Phaeoacremonium aleophilum under field (intact berries) and laboratory (detached berries) conditions. In one test, berries were injured by pricking the skin with a syringe needle to a depth of approximately 1.5 mm. Brown to purple lesions appeared 5 to 7 days after inoculation in both the injured intact and detached berries. Lesions on these berries were larger when inoculated earlier in the season indicating that young, immature berries are more susceptible to infection than mature berries. In another test, berries were injured by rubbing the skin with carborundum dust using a cotton-tipped applicator. Esca-like lesions developed in 4 to 5 days after inoculation of detached but not intact berries. Occasional infection of non-injured berries occurred which appeared as small dots to pin-head size lesions around the lenticels. Scanning electron microscopy observations of these lesions showed abundant hyphal growth on the surface with apparent penetration through lenticels; however, fungal structures were not detected with certainty beneath the lenticels or intact cuticle. In both tests, the fungi were re-isolated from the advancing margin of the lesions.

Evaluation and structure–activity relationship of synthesized cyclohexanol derivatives on percutaneous absorption of ketoprofen using artificial neural network

The effect of 35 newly synthesized O-ethylmenthol (MET) derivatives on percutaneous absorption of ketoprofen was investigated in rats. In order to understand the relationship between the structure of compounds and promoting activity (structure–activity relationship), an artificial neural network (ANN) was employed. In the in vivo percutaneous absorption study, male Wistar rats, weighing 160–180 g, were used. The apparent penetration rate ( R p) was estimated based on a pharmacokinetic model with a constant rate of penetration through the skin after a lag time. As an index of the promoting activity of each compound, an enhancement factor (Ef), defined as follows, was used: Ef= R p(with enhancer)/ R p(without enhancer). An irritation evoked on rat skin was microscopically judged at the end of the in vivo percutaneous absorption experiment and evaluated as a total irritation score (TIS). Ef and TIS were selected as output variables to determine the ANN structure. Calculated log P, molecular weight, steric energy (SE), van der Waals area, van der Waals volume, dipole moment, highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) were used as factors to determine the structural nature of cyclohexanol derivatives. Among these parameters, log P, SE and LUMO significantly affected the prediction of Ef and TIS. The predicted values of Ef and TIS coincided well with in vivo percutaneous absorption experimental values. However, results observed with a linear regression method were poor compared with the ANN approach. The contribution index of log P was ≈50% in the prediction of Ef, suggesting that lipophilicity among physicochemical properties contributes most of the promoting activity of these compounds.

Effect of synthesized cyclohexanol derivatives using l-menthol as a lead compound on the percutaneous absorption of ketoprofen

l-Menthol was selected as a lead compound to synthesize new candidates for percutaneous absorption enhancers. In a previous study, O-ethylmenthol (MET) was the most effective compound and caused relatively little skin irritation. To develop more effective compounds, mono- or disubstitute groups of cyclohexane with an O-ethyl group were synthesized. Some 35 compounds were synthesized and evaluated for their promoting activity and effect on skin. An in vivo percutaneous absorption study was performed using rats with hydrogel containing ketoprofen and each of the synthesized compounds. The plasma concentration of ketoprofen was determined after the application of hydrogel to the abdominal area of rats. The apparent penetration rate ( R p) was estimated based on the pharmacokinetic model with a constant rate of penetration through the skin after the lag time. The 2-compartment model was applied to the data obtained from the iv administration. As an index to evaluate the promoting activity of each enhancer, an enhancement factor ( E f) was defined as follows: E f= R p (with enhancer)/ R p (without enhancer). Irritation to skin was pathologically evaluated. The treated area of rat abdominal skin was exised after the in vivo experiment using total irritation score (TIS). The compound having a C-3 positioned iso-butyl group on the chemical structure was the most effective and caused relatively little irritation among mono-substituted compounds. In the case of di-substituted compounds, all had the same effect as or a stronger effect than MET. Furthermore, the promoting activity almost corresponded to irritation. To estimate log P, one of the physicochemical properties of molecules, a computer program ‘CAChe’ was employed. The log P was calculated using the atom typing scheme. Multiple regression analysis revealed that the relations between E f or TIS and log P were parabolic. It was suggested that the optimum log P value reflects the promoting activity to enhance percutaneous absorption of ketoprofen.

Thiomenthol Derivatives as Novel Percutaneous Absorption Enhancers

Thiomenthol derivatives were synthesized and their promoting activity on the percutaneous absorption of ketoprofen from hydrogels was evaluated in rats. The apparent penetration rate (Rp) of ketoprofen absorbed from the hydrogel was estimated by the pharmacokinetic model derived under the assumption of a constant penetration rate through the skin after a lag time. As an index of promoting activity of thiomenthol derivatives, an enhancement factor (Ef) was defined as the ratio of the Rp value with enhancer to the value obtained with the control not containing enhancer. Skin irritancy evoked by these derivatives was investigated microscopically by using a cross-section of the excised skin onto which ketoprofen hydrogel was applied. Total irritation score (TIS) was estimated by summation of each irritation score in several parts of the skin. The physicochemical parameters of thiomenthol derivatives such as a partition coefficient (log P) and a steric energy were calculated and the quantitative relationships between these parameters and the Ef values or TIS values were investigated on the basis of multiple regression analysis. As a result, a parabolic relationship between log P and Ef was noted. A similar relationship was also observed in the case of TIS.

RF-studies of vortex dynamics in isotropic type-II superconductors

We have measured the surface impedance of thick superconductors in the mixed state over a broad 2 kHz–20 MHz frequency range. The depinning cross-over is observed, but it is much broader than expected from classical theories of pinning. A striking result is the existence of size effects which invalidate the common interpretation of the low-frequency surface inductance in terms of a single penetration depth. Instead, a two-mode description of vortex dynamics, assuming free vortex flow in the bulk and surface pinning, accounts quantitatively for the spectrum of the complex apparent penetration depth.

Harmonic flux penetration of superconductors in low-frequency, high-amplitude, alternating-current magnetic fields

A critical-state model has been used to calculate the magnetic response of a superconducting sample to an applied a.c. magnetic field. The analysis has been performed for both a cylindrical and a slab geometry and evaluated up to the tenth harmonic. It is shown that standard expressions derived using the critical-state model which relate the critical current density to the d.c. magnetic moment can be used in a.c. measurements to within an accuracy of by replacing the term for the d.c. magnetic moment by , where is the minimum lossless rms magnetic moment; the apparent penetration of the field beyond the centre of the sample (i.e. an overshoot) found in flux penetration measurements is an artifact of the analysis and cannot be used as direct evidence for granularity. Flux penetration measurements on non-granular NbTi from 4.2 K up to in magnetic fields up to 10 T are presented which provide good agreement with calculations.

In vitro skin penetration and degradation of enkephalin, elcatonin and insulin.

The work described in this paper was designed to evaluate the relevance of in vitro skin penetration studies of peptides across rat skin. The apparent penetration of three peptides, enkephalin, elcatonin and insulin, in the presence of enhancers was not seen in the in vitro method using Franz diffusion cells. However, when a protease inhibitor was mixed in the receptor fluid, the penetration of enkephalin and insulin was observed. Although insulin penetrated in the presence of enhancers, the penetration was extremely small in quantity and the cumulative amount did not increase with time. When the degradation of peptides in the receptor fluid of Franz cell was estimated, these peptides, especially enkephalin and insulin, were rapidly hydrolyzed and were almost completely lost within 3 h in the absence of an inhibitor, while elcatonin was slowly degraded. The addition of protease inhibitors, such as gabexate (20 mM), camostat (20 mM) or bile salt (taurocholate and deoxycholate, 10 mM), to the receptor fluid inhibited the degradation to a considerable extent, with the first-order rate constants decreased to one-tenth compared with the constants without inhibitors. From the inhibitory study using specific inhibitors, it was clarified that enkephalin and elcatonin were mainly hydrolyzed by aminopeptidases, endopeptidases and serine proteases in the viable skin. Consequently, the results obtained from the in vitro penetration studies without inhibitors did not reflect reliable penetration data. Thus, effective protease inhibitor(s) should be used to obtain the data corresponding to the in vivo transdermal experiment. This methodology will provide a means to eliminate the confounding effect of metabolism in permeation experiments.