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PubMedDate not supplied

Optical investigations to avoid the disturbing influences of furrows and wrinkles quantifying penetration of drugs and cosmetics into the skin by tape stripping.

Furrows and wrinkles, as typical structures of human skin, represent a reservoir for topically applied substances. This reservoir can influence penetration experiments of topically applied substances into the stratum corneum by tape stripping. Optical methods such as laser-scanning microscopy, optical coherent tomography, and the microscopical investigation of histological sections obtained by biopsies were used to check a special protocol, which avoids these potential disturbances. The use of a transparent adhesive film with high flexibility and the realization of an intense contact to the stretched skin by pressing the tape with a roll, moved laterally on the tape, are the prerequisites to obtain correct data. The application of this experimental technique and the performance of tape stripping allow the determination of the horny layer profile and the local distribution of topically applied substance, undisturbed by the characteristic structure of the natural skin. These results demonstrate that the presented tape stripping procedure is a valuable tool to determine, quantitatively, the penetration and the bioavailability of drugs and cosmetics inside the human stratum corneum, in relation to the horny layer profile.

Artifacts↗
PubMed1966

Cutaneous water loss in reptiles.

Cutaneous and respiratory evaporation were compared in five species of reptiles at 23 degrees C. There seemed to be a clear correlation between water loss and aridity of the animal's habitat, total evaporation from the desert lizard Sauromalus obesus being about 5 percent of that from the crocodilian Caiman sclerops. Cutaneous evaporation was the major avenue of water loss in all animals examined. This is contrary to the common belief that reptilian skin is practically impermeable to water.

Animals↗
PubMed1968

Stomatal opening: role of potassium uptake by guard cells.

Stomata in isolated epidermal strips open in response to light plus air free of carbon dioxide when the strips are floated on potassium chloride solutions of low concentrations. This opening depends on the stimulation of active accumulation of potassium in quantities sufficient to account for the observed changes in solute potential of the guard cells.

Biological Transport, Active↗
PubMed1984

Effect of azone and propylene glycol on penetration of trifluorothymidine through skin and efficacy of different topical formulations against cutaneous herpes simplex virus infections in guinea pigs.

Tropical formulations of 5-trifluoromethyl-2'-deoxyuridine (TFT) containing different concentrations of TFT, Azone (Nelson Research and Development, Irvine, Calif.), and propylene glycol were evaluated for their potential efficacy in the treatment of cutaneous herpes simplex virus infections by in vitro studies of TFT penetration through skin and in vivo studies of therapeutic activity against herpes simplex virus type 1 infections in the dorsal cutaneous guinea pig model. Azone dramatically increased TFT penetration through human and guinea pig skin. Unexpectedly, high concentrations of propylene glycol were also associated with increased penetration. Studies in the guinea pig model revealed increased efficacy with Azone-propylene glycol-containing formulations, consistent with the in vitro drug diffusion results. A formulation containing 1% TFT, 5% Azone, and 80% propylene glycol decreased lesion area, in comparison to the drug vehicle control, more effectively than 5% acyclovir in polyethylene glycol (reduction of 70 versus 46%, P = 0.03). These studies demonstrate the value of penetration-enhancing agents and the need for careful preclinical evaluations in the development of topical antiviral agents.

Administration, Topical↗
PubMed1985

Comparison of topically applied 5-ethyl-2'-deoxyuridine and acyclovir in the treatment of cutaneous herpes simplex virus infection in guinea pigs.

Three percent 5-ethyl-2'-deoxyuridine (EdU) in an aqueous cream base was compared with 5% acyclovir (ACV) in polyethylene glycol ointment and 3% EdU in 95% dimethyl sulfoxide (DMSO) for efficacy in the topical treatment of an experimental dorsal cutaneous herpes simplex virus type 1 infection in guinea pigs. Topical ACV treatment reduced the mean lesion number by 15%, the lesion area by 32%, and the lesion virus titer by 60% when compared with measurements at contralateral sites treated with the vehicle alone. Application of 3% EdU cream was more beneficial, effecting reductions of 29, 44, and 68% in the same measurements. EdU in DMSO was even more effective, reducing the lesion measurements by 39, 60, and 90%, respectively. The penetration of EdU and ACV through guinea pig skin was compared in single-chamber diffusion cells. In the aqueous cream, EdU readily penetrated excised skin and exhibited rates of flux 10-fold greater than those shown by ACV in ointment formulation (0.56 versus 0.05 microgram/cm2 per h; P = 0.05). The flux of EdU in DMSO was 3.39 micrograms/cm2 per h, six times higher than the flux in the cream vehicle. EdU was more effective than ACV in this experimental animal model, most likely due to better percutaneous drug delivery of EdU from the cream and DMSO vehicles.

Acyclovir↗
PubMed2000

Sodium lauryl sulfate increases the efficacy of a topical formulation of foscarnet against herpes simplex virus type 1 cutaneous lesions in mice.

The influence of sodium lauryl sulfate (SLS) on the efficacies of topical gel formulations of foscarnet against herpes simplex virus type 1 (HSV-1) cutaneous infection has been evaluated in mice. A single application of the gel formulation containing 3% foscarnet given 24 h postinfection exerted only a modest effect on the development of herpetic skin lesions. Of prime interest, the addition of 5% SLS to this gel formulation markedly reduced the mean lesion score. The improved efficacy of the foscarnet formulation containing SLS could be attributed to an increased penetration of the antiviral agent into the epidermis. In vitro, SLS decreased in a concentration-dependent manner the infectivities of herpesviruses for Vero cells. SLS also inhibited the HSV-1 strain F-induced cytopathic effect. Combinations of foscarnet and SLS resulted in subsynergistic to subantagonistic effects, depending on the concentration used. Foscarnet in phosphate-buffered saline decreased in a dose-dependent manner the viability of cultured human skin fibroblasts. This toxic effect was markedly decreased when foscarnet was incorporated into the polymer matrix. The presence of SLS in the gel formulations did not alter the viabilities of these cells. The use of gel formulations containing foscarnet and SLS could represent an attractive approach to the treatment of herpetic mucocutaneous lesions, especially those caused by acyclovir-resistant strains.

Administration, Topical↗
PubMed2005

Pharmacokinetics of oritavancin in plasma and skin blister fluid following administration of a 200-milligram dose for 3 days or a single 800-milligram dose.

Oritavancin is a novel glycopeptide currently being developed for the treatment of complicated skin and skin structure infections (cSSSI), including those caused by multidrug resistant gram-positive pathogens. The disposition of oritavancin in skin structures was investigated using a cantharide-induced blister fluid model. Seventeen healthy male subjects received oritavancin, but only 16 subjects were evaluated after one subject discontinued study drug. Each subject (eight per dose group) received 200 mg of oritavancin once a day for 3 days (group A) or 800 mg as one single dose (group B). Group A plasma samples and exudates from blister fluid were collected on days 3, 4, 7, 9, and 12 and on days 3, 4, 7, and 9, respectively. Group B samples and exudates were collected on days 1, 2, 5, 7, and 10 and on days 1, 2, 5, and 7, respectively. Drug concentrations were determined using a liquid chromatography-tandem mass spectrometry assay and, subsequently, pharmacokinetic analysis was performed. Differences between treatment groups in ratios for area under the concentration-time curve for blister fluid and plasma (AUC(blister fluid)/AUC(plasma) ratios) were evaluated using a t test (alpha = 0.05). Mean maximum concentration of drug in plasma or blister fluid was approximately 8-fold and 11-fold higher in plasma than in blister fluid following the 200- or 800-mg doses of oritavancin, respectively. Mean AUC(blister fluid)/AUC(plasma) ratios at 24 h were 0.190 (standard deviation [SD], 0.052) and 0.182 (SD, 0.062) for groups A and B, respectively (P = 0.791). To place these results in a clinical context, mean drug concentrations in blister fluid exceed the oritavancin MIC at which 90% of strains are inhibited of Staphylococcus aureus (2 microg/ml) by approximately 2- to 5.5-fold at 12 h and 1.5- to 3-fold at 24 h following administration of both dosing regimens. These results support the potential use of oritavancin for the treatment of cSSSI.

Adult↗
PubMed1979

Glyceryl trinitrate ointment in angina pectoris.

Skin absorption of glyceryl trinitrate (GTN) has been recognized for a long time. The effect of GTN and a placebo ointment in prevention of chest pain has been assessed and compared by studying the exercise capacity in 17 patients with angina pectoris. The placebo cream was ineffective but the GTN ointment was found to have beneficial effect in relief of pain in 16 cases. This was established by the patients' capacity to exercise on a bicycle ergometer without chest pain. The beneficial effect was sustained for up to 3 hr in 12 patients. This preparation appears to act as a long-acting nitrate and may be valuable for patients in whom beta-blocking agents are ineffective or contra-indicated, and surgery is not feasible.

Adult↗
PubMed1982

Pneumonia in sheep associated with dipping in carbolic dips.

Fourteen outbreaks of pneumonia in sheep following dipping in carbolic dips were investigated at seven laboratories. Deaths commonly occurred between one and three days after dipping and fat young sheep of the Suffolk and Border Leicester breeds were most usually involved in outbreaks. The pneumonia was characterised by hyperaemic, oedematous and cyanotic lungs, and the main histological features were hyperaemia, fluid and cellular exudation into alveolar spaces, and widespread epithelialisation of alveolar walls. The microscopic changes differed from pneumonic pasteurellosis and no significant organisms were recovered from any of the lungs. One of 27 Dorset Horn lambs dipped in a batch of dip which had been incriminated in some episodes developed an epithelialising interstitial pneumonia, while two out of three Suffolk lambs dipped in twice the recommended strength of the same batch of dip became ill with severe pneumonia, apparently following skin absorption.

Animals↗
PubMed2004

In vitro evaluation of percutaneous diffusion of uranyl nitrate through intact or excoriated skin of rat and pig.

At the present time, the International Commission on Radiological Protection (ICRP) has not published any model concerning internal radioactive contamination by uptake from wounds. The aims of our work were to determine the time available to treat contamination of intact or wounded skin before a significant uptake of uranium occurred and to evaluate the consequences of incomplete decontamination on uranium uptake. The kinetics of percutaneous diffusion of uranium through intact or excoriated skin and its distribution in skin layers were evaluated using an in vitro technique. Our data demonstrated a dramatic increase of uranium percutaneous diffusion through excoriated skin compared with intact skin. Significant uptake of uranium through excoriated skin occurred in only 30 min, indicating that there is only a short interval available to treat a contaminated wound effectively. Moreover, in the case of an incompletely decontaminated superficial wound, viable epidermis behaved as a reservoir for uranium that remained bioavailable. At the present time, potential uptake of uranium and perhaps other radionuclides through intact or wounded skin is not adequately taken into account by radiological protection agencies. Our results emphasize the need for further study and modeling of uptake of radionuclides through intact or wounded skin.

Administration, Cutaneous↗