The role of trace elements in psoriatic patients undergoing balneotherapy with Dead Sea bath salt.
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BACKGROUND: A beneficial effect was observed in patients with psoriasis vulgaris following balneotherapy with Dead Sea bath salt. OBJECTIVES: To evaluate the possible role of trace elements in the effectiveness of balneotherapy. METHODS: Serum levels of 11 trace elements were analyzed in 23 patients with psoriasis vulgaris who participated in a double-blind controlled study of balneotherapy with either Dead Sea bath salt (12 patients) or common salt (11 patients). Thirteen healthy volunteers served as controls. RESULTS: The mean pre-treatment serum levels of boron, cadmium, lithium and rubidium were significantly lower in patients compared to controls, whereas the mean pre-treatment serum level of manganese was significantly higher in patients compared to controls. Balneotherapy with Dead Sea bath salt resulted in a significant decrease (P = 0.0051) in the mean serum level of manganese from 0.10 +/- 0.05 mol/L to 0.05 +/- 0.02 mumol/L. The mean reduction in the serum level of manganese differed significantly (P = 0.002) between responders (% Psoriasis Area and Severity Index score reduction > or = 25) and non-responders (% PASI score reduction < 25). Following balneotherapy with Dead Sea bath salt the mean serum level of lithium decreased in responders by 0.01 +/- 0.02 mumol/L, whereas its level in non-responders increased by 0.03 +/- 0.03 mumol/L. (P = 0.015). CONCLUSIONS: Manganese and lithium may play a role in the effectiveness of balneotherapy with Dead Sea bath salt for psoriasis. (+info)
A combination of iontophoresis and the chelating agent 1,10 phenanthroline act synergistically as penetration enhancers.
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The peroxovanadium compound VO(O2)2 1,10 phenanthroline (bpV(phen)) is capable of lowering blood glucose levels. It is not available in oral form, but it is effective when delivered transdermally. Iontophoresis can significantly reduce the lag time of this response in vivo when compared with passive penetration. To better mimic in vivo insulin release, we explored the effects of various iontophoretic current durations on dermal penetration of bpV(phen). Iontophoretic transport was not related to total applied charge, as steady-state flux was equivalent for current durations ranging from 15 minutes to 9 hours. We hypothesized that the unexpectedly large transport after just 15 minutes of current was caused by an increase in passive penetration of bpV(phen) induced by iontophoresis. Iontophoretic pretreatment with the chelating agent 1,10 phenanthroline increased passive penetration of bpV(phen), whereas neither the nonchelating isomer 1,7 phenanthroline nor the less potent chelator EDTA were effective. The use of 1,10 phenanthroline as a penetration enhancer for other chemicals was examined with the amino acids alanine and leucine. Fifteen minutes of 1,10 phenanthroline iontophoresis enhances alanine transport 11.4-fold over passive, whereas the 1,7 phenanthroline increased transport by a factor of 4.6 and the iontophoretic control of ethanol by 1.9. Surprisingly, phenanthroline did not enhance 3H leucine penetration. The reasons for this selectivity are not clear and warrant further investigation. Overall, the data suggest that chelating agents, specifically 1,10 phenanthroline, may be used as penetration enhancers for the delivery of certain compounds. (+info)
Histological and ultrastructural studies of rats exposed to carbaryl.
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The aim of the study was to assess the general toxic effects of dermally applied carbaryl, based on histological and ultrastructural examinations of internal organs and to relate these effects to earlier own studies where 14C carbaryl was used for determining the pesticide penetration. The pesticide was applied in doses of 1/5 and 1/10 LD50, administered to the tail skin of male Wistar rats 4 hours daily, for 4 weeks except Saturdays and Sundays. After the experiment, the animals were anaesthetized and the following organs were taken for histological study: brain, lung, heart, liver, kidney, skin from the site of exposure and skin from a place at least 2 cm distant from the exposure site. Lung, liver, kidney, heart and skin were used for ultrastructural studies. Dermal application of carbaryl resulted only in slight histological changes in skin, liver, brain and lung. Even in brain and liver, where large amounts of 14C carbaryl, compared to other organs (lung, kidney, heart), where the intensity of histologic changes was earlier stated to below. Ultrastructural changes were observed in skin, liver, lung, heart and kidney. (+info)
Neurotoxic effect of dermally-applied chlorpyrifos and cypermethrin in Wistar rats.
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The aim of the study was to evaluate the neurotoxic effect of a dermally-applied mixture of chlorpyrifos and cypermethrin in rats based on cognitive function, activity of the blood cholinesterase and brain acetylcholinesterase, as well as histologic brain examination. Nurelle D 550 EC (500 g of chlorpyrifos and 50 g of cypermethrin) was used in the study. The application liquid was in the form of a water solution. The investigation covered eight groups of animals: six experimental groups and two control groups, of 15 rats each. Experimental groups received 5.6 mg/cm2 chlorpyrifos and 0.5 mg/cm2 cypermethrin, or 27.8 mg/cm2 chlorpyrifos and 2.7 mg/cm2 cypermethrin dermally, for one day, one week and four weeks, except for Saturdays and Sundays. The preparations examined were applied to the tail skin of rats. The animals were anaesthetized at the end of exposure period. Plasma cholinesterase and brain acetylcholinesterase activities were determined. The brain for histological examination was perfused with a solution of methanol, formalin and glacial acetic acid, and the sections stained by the Nissel method. The behaviour of the animals was evaluated in the open field test four times: before exposure, and after one, two and four weeks of the experiment. The results of the study showed that chlorpyrifos and cypermethrin applied in a mixture caused an inhibition of cholinesterase and acetylcholinesterase activity and elicited the pycnosis of brain neurocytes. (+info)
In vitro skin permeation of morphine hydrochloride during the finite application of penetration-enhancing system containing water, ethanol and l-menthol.
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The effects of composition of applied solutions, containing water, ethanol (EtOH) and l-menthol (LM) as penetration enhancers, on the in vitro permeation of morphine hydrochloride (MPH) through excised hairless rat skin were examined in finite application experiments. Three of the five different applied solutions contained almost saturated LM and two contained levels of LM below the limit of solubility. Despite similar pseudo steady-state fluxes (maximum fluxes observed) of MPH from the solutions, lag time for the permeation of MPH from the saturated systems was shorter than that from the unsaturated systems. Lag times for the permeation of EtOH and LM from the saturated systems were also shorter than those from the unsaturated systems. Thermodynamic activity of LM is important for the enhancing effect against MPH permeation. At the beginning for the permeation experiment, the activity of LM in the unsaturated systems was lower than that in the saturated solutions. As the skin permeability of EtOH was higher than that of other components, the content of EtOH in the applied solution gradually decreased with time, while the activity of LM increased eventually showing a sufficient enhancing effect. Solvent drag effect was not important for the permeation of MPH, since penetration rate of MPH was independent of the time course of that of EtOH. The amount of LM migrating into skin appeared to be the most important parameter for the penetration-enhancing effect of the mixed system in the in vitro permeation of MPH through excised hairless rat skin. (+info)
Prediction of plasma concentration of GTS-21 in hairless rats following monolithic transdermal delivery.
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The transdermal therapeutic systems (TTS) usually achieve constant plasma concentration for an extended period of time. This is because a sufficient drug stored in the device can keep the constant concentration on the surface of the stratum corneum during the system application. When the drug molecules are not enough to provide the constant surface concentration, the rate of drug penetration decreases with time because of decreased supply of the drug molecules from the delivery device. This paper has proposed an empirical simple approach to predict the plasma concentration for such a TTS. A novel compound, GTS-21, for Alzheimers' disease currently under development was used as a model drug. In vivo and in vitro experiments were carried out in hairless rats. The in vivo plasma concentration-time profile in hairless rats following the application of TTS well agreed with the predicted profile based on the skin pharmacokinetic model together with the model parameters determined from the in vitro experiment. (+info)
Prediction of human skin permeability using a combination of molecular orbital calculations and artificial neural network.
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This study was carried out to develop a novel method for predicting the skin permeability coefficient (log K(p)) of compounds from their three-dimensional molecular structure using a combination of molecular orbital (MO) calculation and artificial neural network. Human skin permeability data on 92 structurally diverse compounds were analyzed. The molecular descriptors of each compound, such as the dipole moment, polarizability, sum of charges of nitrogen and oxygen atoms (sum(N,O)), and sum of charges of hydrogen atoms bonding to nitrogen or oxygen atoms (sum(H)) were obtained from MO calculations. The correlation between these molecular descriptors and log K(p) was examined using feed-forward back-propagation neural networks. To improve the generalization capability of a neural network, the network was trained with input patterns given 5% random noise. The neural network model with a configuration of 4-4-1 for input, hidden, and output layers was much superior to the conventional multiple linear regression model in terms of root mean square (RMS) errors (0.528 vs. 0.930). A "leave-one-out" cross-validation revealed that the neural network model could predict skin permeability with a reasonable accuracy (predictive RMS error of 0.669). (+info)
PBPK modeling of the percutaneous absorption of perchloroethylene from a soil matrix in rats and humans.
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Perchloroethylene (PCE) is a widely used volatile organic chemical. Exposures to PCE are primarily through inhalation and dermal contact. The dermal absorption of PCE from a soil matrix was compared in rats and humans using real-time MS/MS exhaled breath technology and physiologically based pharmacokinetic (PBPK) modeling. Studies with rats were performed to compare the effects of loading volume, concentration, and occlusion. In rats, the percutaneous permeability coefficient (K(P)) for PCE was 0.102 +/- 0.017, and was independent of loading volume, concentration, or occlusion. Exhaled breath concentrations peaked within 1 h in nonoccluded exposures, but were maintained over the 5 h exposure period when the system was occluded. Three human volunteers submerged a hand in a container of PCE-laden soil for 2 h and their exhaled breath was continually monitored during and for 2.5 h following exposure. The absorption and elimination kinetics of PCE were slower in these subjects than initially predicted based upon the PBPK model developed from rat dermal kinetic data. The resulting K(P) for humans was over 100-fold lower than for the rat utilizing a single, well-stirred dermal compartment. Therefore, two additional PBPK skin compartment models were evaluated: a parallel model to simulate follicular uptake and a layered model to portray a stratum corneum barrier. The parallel dual dermal compartment model was not capable of describing the exhaled breath kinetics, whereas the layered model substantially improved the fit of the model to the complex kinetics of dermal absorption through the hand. In real-world situations, percutaneous absorption of PCE is likely to be minimal. (+info)