The diffusion of nandrolone through hydrated human cadaver skin

Effective diffusion constants have been determined for the permeation of nandrolone through whole and stripped human abdominal cadaver skin in vitro. From the values obtained, the diffusion constant for nandrolone in the stratum corneum has been inferred. The experimental approach used yields reproducible results for skin samples taken from a single individual. There is also a surprising degree of uniformity in the values obtained for skin from different individuals.     

Programmed diffusional release rate from encapsulated cosolvent system

The programmed diffusional release rate of an active agent through a rate-controlling membrane from a cosolvent system is discussed. At initial conditions, the drug is present below saturation in solution in a solvent mixture, enclosed by the rate-controlling membrane; the solvent is composed of the main solvent and a consolvent, which increases the drug solubility in the main solvent. During operation, the active agent and cosolvent diffuse from the capsule at a rate controlled by the membrane. Equations were derived describing the release rate of the active agent as a function of the permeability of the cosolvent and agent, the capsule dimensions, and the system's initial conditions. A great variety of release rate profiles can be programmed from declining to increasing delivery rate patterns as a function of time. Experimental data are presented for the drug progesterone in solution in cyclohexane with methyl, heptyl, or cetyl alcohol as the cosolvent in a polyethylene capsule. The theory qualitatively predicts the theory qualitatively predicts the experimental results.     

The rate of telomere sequence loss in human leukocytes varies with age

A gradual loss of telomeric repeat sequences with aging previously has been noted in normal adult tissues, and this process has been implicated in cell senescence. No data exist that address the rate of telomere shortening in normal human cells within families or early in life. To address these questions, we measured telomere lengths in peripheral blood leukocytes (PBLs) from 75 members of 12 families and in a group of unrelated healthy children who were 5-48 months old. Here we report the surprising observation that rates of telomere attrition vary markedly at different ages. Telomeric repeats are lost rapidly (at a rate of >1 kilobase per year) from the PBLs of young children, followed by an apparent plateau between age 4 and young adulthood, and by gradual attrition later in life. These data suggest that the loss of telomeric repeats in hematopoietic cells is a dynamic process that is differentially regulated in young children and adults. Our results have implications for current models of how telomeric sequences are lost in normal somatic cells and suggest that PBLs are an excellent tissue to investigate how this process is controlled.     

On the rate of equilibration of diffusional traps in solids

The rate at which the equilibrium boundary condition is attained at an internal diffusion source is considered. The source is a trap site with a binding energy for the diffusing species relative to the bulk lattice. The case of a given initial amount in the trap and the case where the diffusing species is supplied to the trap at a constant rate are considered. The rate of equilibration is found to be more rapid for a short-range trap, where the binding energy is released in one jump, than for a long-range trap. The problem is relevant to solute transport and release by movina dislocations.     

The diffusional transport of water and small solutes in isolated endothelial cells and erythrocytes

The diffusional permeability coefficients, PD, for tritiated water (3HHO) 14C-antipyrine (AP) and 14C-iodoantipyrine (IAP) in isolated calf pulmonary artery endothelial cells and dog erythrocytes are measured with the linear diffusion technique at 11.5, 15, 20 and 37 degrees C. The PD values for both cell populations follow the sequence 3HHO > IAP > AP at each of the temperatures. PD for water is higher in the erythrocyte compared to the endothelial cells. The differences in PD for AP and IAP in the erythrocytes and endothelial cells are not dramatic and are similar to the differences seen in comparing permeation of the same solute through bilayers of different composition. A comparison of the values of PD calculated for the endothelial cells with those for isolated capillaries and the structured endothelium in whole lungs validates the use of the isolated cells as models for the endothelial cells in situ. Incubation of the endothelial cells with cis-vaccenic acid or cholesterol produces a reduction in PD for water and antipyrine. These data are analyzed in terms of Stokesian and non-Stokesian diffusion. The interpretation which best accommodates the data is that the phospholipid area of the membrane, rather than the hydrocarbon core, provides the greatest resistance to permeation for these solutes.     

Percutaneous penetration of 2-phenoxyethanol through rat and human skin

2-Phenoxyethanol applied in methanol was absorbed (64 +/- 4.4% at 24 hr) through unoccluded rat skin in vitro in the static diffusion cell with ethanol/water as receptor fluid. By comparison (43 +/- 3.7% in 24 hr) was absorbed in the flow-through diffusion system with tissue culture medium as receptor fluid. 2-Phenoxyethanol applied in methanol was absorbed (59.3 +/- 7.0% at 6 hr) through unoccluded human skin in vitro in the flow-through diffusion cell with tissue culture medium. With both unoccluded cells, 2-phenoxyethanol was lost by evaporation but occlusion of the static cell reduced evaporation and increased total absorption to 98.8 +/- 7.0%. Skin, post mitochondrial fraction, metabolized phenoxyethanol to phenoxyacetic acid at 5% of the rate for liver. Metabolism was inhibited by 1 mM pyrazole, suggesting involvement of alcohol dehydrogenase. However, first-pass metabolism of phenoxyethanol to phenoxyacetic acid was not detected during percutaneous penetration through viable rat skin in the flow-through system. First-pass metabolism in the skin does not therefore have an influence on systemic availability of dermally absorbed phenoxyethanol. These measures of phenoxyethanol absorption through rat and human skin in vitro agree well with those obtained previously in vivo.     

Effect of environmental conditions on the penetration of benzene through human skin

The in vitro penetration of [14C]benzene through freshly prepared human skin was examined under a variety of skin conditions associated with swimming and bathing. The experimental system utilized a recirculating donor solution and a flow-through receiver solution, and was modified to accommodate the analysis of volatiles. The permeability coefficient of 0.14 cm/h under standard conditions at 26 degrees C was found to increase to 0.26 cm/h at 50 degrees C and decrease to 0.10 cm/h at 15 degrees C. Storage of the skin at- 20 degrees C did not affect the penetration of benzene. Application of baby oil, moisturizer, or insect repellant to the skin before exposure under standard conditions did not affect the flux of benzene, but a significant increase was observed when the skin was pretreated with sunscreen (permeability coefficient 0.24 cm/h). These results suggest that risk assessment or exposure modeling for benzene and other environmental contaminants should account for appropriate changes in the environmental conditions when considering the dermal route of exposure.     

Oral contraceptives alter circadian rhythm parameters of cortisol, melatonin, blood pressure, heart rate, skin blood flow, transepidermal water loss, and skin amino acids of healthy young women

This study investigated the usage consumption pattern and chemical composition of fermented foods consumed in 191 rural households (1030 individuals) in Emene. The result showed that fermented foods were widely used and consumed by most age groups (under 2 years to adults) because of poor socioeconomic status. Fermentation period varied with type of food and was mostly carried out as a means of detoxifying certain foods. Generally, fermented foods contributed substantially to the daily caloric (46.3 to 79.9% for males and 57.5 to 78% for females); calcium (33.8 to 63.5% for males and 48.3 to 55.4% for females); iron (34.4 to 58.6% for males and 47.4 to 74.6% for females); and thiamin (23 to 58.5% for males and 37.5 to 60% for females) intakes. The contributions of fermented foods to protein (10 to 40.7%) and ascorbic acid (1.9 to 18.7%) intakes were however, low. When compared with the FAO recommendations, the daily intakes of protein, calcium, riboflavin, niacin and ascorbic acid by the subjects were low due to large consumption of starchy root crops. Poor financial status was the most limiting factor to adequate nutrient intake. Such results point out the need for nutrition education related to improved methods of preparation and food selection.     

A novel method to determine the diffusional water permeability of oocyte plasma membranes

Measurements of the cell membrane diffusional water permeability (Pd) are important to characterize water passage across water channels and across the lipid bilayer component of the membrane. Existing methods for those measurements are involved; however, we report here a simple procedure to estimate Pd in Xenopus laevis oocytes and similar large cells. Due to the different densities of H2O and D2O (heavy water), an oocyte transferred from normal medium to a D2O-based medium floats initially, but subsequently sinks when a certain amount of the water originally in them is replaced by the D2O that diffuses in. We describe how the 'flotation time' (time that oocytes float in a heavy water solution before they start sinking) yields the Pd of the plasma membrane. Determination of Pd by this procedure and by the rate of tritiated water (T2O) efflux give for Pd results which are very close: 2.2 +/- 0.2 (n = 8) and 2.0 +/- 0.1 (n = 6) microns/s, respectively (T = 10 degrees C). Furthermore, our method detects the increase in Pd elicited in oocytes by either expression of water channel proteins, or by treating them with the pore-forming antibiotic amphotericin B. This method appears useful to gauge the expression and function of pore-forming, water-permeable membrane proteins.     

Permeation characteristics of 8-methoxypsoralen through human skin; relevance to clinical treatment

The permeation characteristics through human skin of 8-methoxypsoralen (8-MOP) and its physical attributes were investigated. The log octanol/water partition coefficient and saturated aqueous solubility of 8-MOP at 32 degrees C were 1-98 and 55.8 micrograms mL-1 respectively, 8-MOP showed Fickian diffusion, with its flux being linearly related to the concentration of drug in the donor solution. The permeability coefficient of 8-MOP through human skin from different concentrations of aqueous solutions and a 2.6 micrograms mL-1 bath lotion (as used in clinics) were statistically identical with mean values of 1.76 +/- 0.12 x 10(-2) and 1.70 +/- 0.32 x 10(-2) cm h-1 respectively (P > or = 0.05). An ethanol/water (1:1 w/v) receptor solution did not improve the clearance of 8-MOP from the dermis when compared with an aqueous vehicle. Complete removal of the stratum corneum by tape stripping from full-thickness membranes produced a threefold increase in the flux of 8-MOP thus suggesting that the main barrier to 8-MOP permeation resides in the stratum corneum although the aqueous epidermal and dermal tissue provide a significant resistance to transdermal drug permeation. The equilibrium uptake of 8-MOP into psoriatic plaques and the 8-MOP aqueous plaque partition coefficient were found to be more than twofold greater than for normal stratum corneum. The absorption of 8-MOP from the total applied topical dose (396 mg) was assessed as approximately 0.25% and only 2.5% of an oral dose, a significant reduction in the possible toxic hazard. The peak concentration of 8-MOP permeating through the skin was observed at about 35 min after limited exposure for 15 min. Our results suggest that following a 15 min bath in the drug solution, there may be a need for an interval of about 20 min before patients are irradiated to ensure the optimization of photosensitizer with UVA irradiation (PUVA) therapy. Alternatively, UV irradiation could be applied at a lower flux over a longer time.     

The rate of periodontal attachment loss in subjects with established periodontitis

A stepwise approach to determine attachment level changes was utilized to assess the nature of progression of periodontal disease. Following initial screening, 51 subjects with established periodontitis were monitored quarterly for 9 more months. Probing depth (PD) and relative attachment level (RAL) were recorded using an automated, pressure sensitive probe system. To establish intra-examiner error, repeated measurements were performed for all sites at the final visit. An overall standard deviation (SD) for RAL repeated measurements was initially calculated (0.76 mm) using all 6,935 double measurements. Sites were sorted by factors which contribute to the error of attachment level measurements; i.e., pocket depth (shallow, moderate, deep), tooth type (molar, non-molar) and location (buccal, lingual). Data were sorted by the above 12 groups, and SD for repeated measurements was calculated separately for them. The ratio between these SD and the overall SD served as the corrective factor. Each patient's initial threshold (2 SD) was multiplied by these corrective factors thus resulting in 12 thresholds for each subject. Next, linear, exponential and logarithmic regression models were tested for each site, and the regression model showing the highest R value was chosen for that site. AL changes were tested against the patient's threshold for that site. Sites with attachment loss exceeding the threshold were deemed active. Five hundred eighty-one sites (8.3%) exhibited attachment loss exceeding the various thresholds. Of these, linear progression occurred in 195, logarithmic in 224, and exponential in 162 sites. Individual patient's attachment loss ranged from 0.6 to 19.4% of all sites.(ABSTRACT TRUNCATED AT 250 WORDS)     

线路的线损率与工程设计中电压损失的关系

根据线路的线损率和电压损失的定义和计算公式,推导和分析了两者之间的关系,提出在工程设计阶段通过计算线路电压损失估算预期的线损率,并对企业常用的供电线路电压损失的控制值提出建议.     

采场矿石贫化率和采矿损失率指标管理的实践

介绍了三山岛金矿采场的矿石贫化率和采矿损失率两率指标管理的实践,分析了影响两率指标的各种因素,采取各种有效措施,就能降低采场的两率指标。     

The electrical characteristics of human skin in vivo

PURPOSE: The objectives of this study were to investigate the impedance properties of human skin in vivo and to examine the effect of iontophoresis upon them. METHODS: Having established the intra- and inter-individual variation in basal values of skin impedance, the effect of varying iontophoretic current density, ionic strength and counter-ion on the rate of recovery of skin impedance after iontophoresis was investigated. RESULTS: Passage of an iontophoretic current caused a significant reduction in the magnitude of the skin impedance. Increasing the current density caused an even greater reduction in the value of the skin impedance and slowed the rate of recovery. Reduction of the ionic strength resulted in an increase in the rate of recovery following iontophoresis. A significant increase in the rate of recovery was observed when CaCl2 replaced NaCl as the electrolyte. Although visual inspection revealed the presence of greater erythema when CaCl2 was used, there was an absence of the mild sensation experienced by volunteers when using NaCl. The last part of the study established a correlation between transepidermal water loss and impedance analysis as complementary methods for probing skin barrier function in vivo. The data were fitted to an equivalent circuit consisting of a resistor in parallel with a constant-phase element and a mechanistic model proposed to explain the electrical properties of the skin. CONCLUSIONS: The first comprehensive investigation of the effect of iontophoresis on the electrical properties of human skin in vivo has been described. It would appear from the results, and from their interpretation, that impedance spectroscopy may be an effective method to quantify the impact of iontophoresis on the skin, and to determine the extent to which proposed drug delivery regimens will perturb skin barrier function.     

Percutaneous penetration of octyl salicylate from representative sunscreen formulations through human skin in vitro

The human skin penetration of [14C]octyl salicylate from two representative sunscreen vehicles was determined in vitro. 3H-sucrose was incorporated into all formulations and provided a marker for membrane integrity. When applied as a finite dose in an oil-in-water emulsion vehicle containing 5% (w/w) octyl salicylate, the average total absorption of 14C over 48 hr was 0.65+/-0.16% of the applied dose (representing a total amount permeated of 1.58+/-0.36 microg/cm2). When applied as an infinite dose in the oil-in-water emulsion vehicle the average total absorption of 14C over 48 hr was 0.47+/-0.22% of the applied dose (representing a total amount permeated of 27.54+/-13.91 microg/cm2). When applied as a finite dose in a representative hydroalcoholic formulation containing 5% (w/w) octyl salicylate, the average total absorption of 14C over 48 hr was 0.59+/-0.09% of the applied dose (representing a total amount permeated of 1.58+/-0.25 microg/cm2). When applied as an infinite dose in the hydroalcoholic formulation the average total absorption of 14C over 48 hr was 0.23+/-0.05% of the applied dose (representing a total amount permeated of 11.28+/-2.55 microg/cm2). The penetration of [14C]salicylic acid [applied at a concentration of 2.7% (w/w), in the oil-in-water emulsion] was also determined. When applied as a finite dose the average total absorption of 14C over 48 hr was 1.14+/-0.23% of the applied dose (representing a total amount permeated of 1.65+/-0.39 microg/cm2). These results suggest that the in vitro human skin permeation of octyl salicylate is relatively low. The amounts of octyl salicylate and salicylic acid permeated when applied in similar vehicles were remarkably similar over 48 hr (1.58 microg/cm2 and 1.65 microg/cm2, respectively). This suggests the possibility that the 14C label appearing in the receptor fluid may, in both cases, represent salicylic acid. If this is the case, then it is possible that the amount of octyl salicylate permeating through the skin is much less than that suggested by the data obtained here. This supposition is, however, entirely speculative and has yet to be confirmed experimentally.     

In vitro percutaneous penetration of methyl-parathion from a commercial formulation through the human skin

OBJECTIVE: To compare in vitro percutaneous absorption of methyl-parathion dissolved in an acetone vehicle and in the form of a commercial formulation. METHODS: Penetration through the human skin was measured in Franz diffusion cells with full thickness skin from a human cadaver as the membrane. The two tailed non-parametric Mann-Whitney U test was used to compare the cumulative diffusion of methyl-parathion in the receptor fluid of the cells at various time intervals. RESULTS: In vitro skin penetration of methyl-parathion was significantly higher with the commercial formulation. The percentage of the applied dose absorbed after 24 hours was 5.20% v 1.35%. The mean lag time was < 8 hours. CONCLUSION: Assessments of uptake and internal dose after exposure to pesticides should be based on the commercial products rather than active ingredients, because of the crucial role of the vehicle, as shown in this study.     

The diffusional formation of ferrite from austenite in Fe-C-Ni alloys

The kinetics of the γ →γ + α phase transformation in a series of Fe-C-Ni alloys containing ∼0.1C (wt pct) and Ni contents ranging from 2.0 to 3.4 (wt pct) have been examined at 700 °C. In agreement with previous investigators, α formation in alloy compositions lying significantly above the calculated local equilibrium-partition/local equilibrium-negligible partition (LE-P/LE-NP) boundary was observed. Neither the paraequilibrium (PE) nor the LE-NP treatments were able to consistently describe the α growth kinetics in all of the alloys over the timeframe investigated. We have proposed a new treatment for α growth, based on the local energy balance at the interface, that allows for the local transport of Ni atoms across the reaction interface and predicts accurately both the fast initial α growth rate and the transition to much more sluggish kinetics that were observed in the alloys with increasing Ni contents. The PE interfacial conditions are the assumed starting point for the model and a continuous transition to local equilibrium conditions is observed with time. This article is based on a presentation given in the symposium “The Effect of Alloying Elements on the Gamma to Alpha Transformation in Steels,” October 6, 2002, at the TMS Fall Meeting in Columbus, Ohio, under the auspices of the McMaster Centre for Steel Research and The TMS-ASM Phase Transformations Committee.     

Permeabilities of alkyl p-aminobenzoates through living skin equivalent and cadaver skin

The in vitro permeabilities of alkyl p-aminobenzoates through living skin equivalent (LSE) and cadaver skin were compared. Methyl, ethyl, and butyl p-aminobenzoates were used as model compounds. The permeabilities of these compounds through LSE and cadaver skin from an aqueous drug suspension were determined with a flow-through diffusion cell. The permeability coefficients of these esters in LSE were an order of magnitude higher than in cadaver skin. This was primarily because of low resistances offered by the outermost layer (i.e., stratum corneum) of LSE. In the case of cadaver skin, the permeability coefficient increased as the carbon chain length increased, whereas no appreciable change in the permeability coefficients of these esters in LSE was observed. These results clearly suggest that the LSE membrane offered very little resistance as opposed to cadaver skin. Therefore, the LSE membrane may not quantitatively represent a good human skin model for evaluating skin permeation of a drug from topical or transdermal formulations.