Penetration of adenosine into excised human skin from binary vehicles: the enhancement factor.

Human skin samples are permeable to adenosine delivered from 0.5-3% solutions in vehicles consisting of propionic acid, hexanoic acid, or mixtures of these in various ratios. The observed optimal Kp, hence flux, of adenosine from the binary vehicles is 0.4 X 10(-3) cm/min, while that from propionic acid is 0.12 X 10(-3), and that from hexanoic acid is 0.16 X 10(-3) cm/min. The bell-shaped dependence of the observed Kp on donor vehicle composition may be resolved into two trends proceeding in opposite directions: an increase in the excess free energy of adenosine in the donor vehicle with an increase in volume fraction of hexanoic acid in that vehicle ("push" effect); and an increase in the flux of adenosine with an increase in the flux of propionic acid ("pull" effect) delivered from the binary vehicle. The Kp of adenosine anticipated from its excess free energy in the donor phase ("push" effect), independent of any enhancing effect due to the presence of propionic acid, is calculated from the partial molal volume of adenosine in a given vehicle; this volume correlates inversely with the solubility parameter of that vehicle. The ratio of the observed Kp to the calculated Kp gives an enhancement factor which is approximately 6 for a formulation consisting of four volumes of hexanoic acid and six volumes of propionic acid. A similar trend is found for binary vehicles of isopropyl myristate and propionic acid.

Penetration of theophylline and adenosine into excised human skin from binary and ternary vehicles: effect of a nonionic surfactant.

A nonionic surfactant, diethyleneglycol lauryl ether (PEG-2-L), increases the flux of either theophylline or adenosine by a factor of 2.2-2.7, when these are delivered from propionic acid solutions into human skin samples, with respect to propionic acid alone. At the same time, the flux of propionic acid from the same vehicles is decreased. Significant expansion of the partial molal volumes vi of both purines occurs following incorporation of PEG-2-L into their propionic acid solution. Hence, the enhancing effect of this surfactant arises mainly from an increase in the excess free energy of these solutes in the donor phase ("push" effect). Paraffin oil increases the flux of either drug from propionic acid by an entirely different mechanism. It enhances the flux of propionic acid into the skin, thus promoting the partitioning of the purine solute in the modified skin barrier ("pull" effect). Indeed, the magnitude of vi of either purine in propionic acid:paraffin oil solution gives no indication of a significant interaction between paraffin oil and the purine solute. Finally, the penetration enhancing effects of PEG-2-L and paraffin oil combined together in the same propionic acid vehicle are additive, resulting in a flux which is approximately the sum total of fluxes obtained separately with PEG-2-L or paraffin oil.

Delivery of theophylline into excised human skin from alkanoic acid solutions: a "push-pull" mechanism.

Human skin samples are permeable to theophylline delivered from 1.5% solutions in various alkanecarboxylic acids and their mixtures. The respective permeability coefficients of theophylline, calculated from steady-state flux, correlate negatively with the permeability coefficients of the donor carboxylic acids and positively with the excess free energy of theophylline in the donor phase, or "push" effect. An exception is propionic acid which enhances the penetration of theophylline by promoting its solubility in the skin-propionic acid medium through the "pull" effect. The two effects operate jointly in the delivery of theophylline from a mixture of propionic and a higher acid such as lauric, resulting in a much higher flux than expected from theory. The "push" effect can be estimated from the solubility parameters of theophylline and those of the holding phases even though regular solution behavior is not strictly obeyed. The increase in the permeability coefficient with partial molal volume of theophylline in the donor phase seems to reach an upper limit or decrease beyond 119 cm3.mol-1.

Rhinoscleroma in an octogenarian woman.

Rhinoscleroma, a granulomatous infection caused by Klebsiella rhinoscleromatis and usually afflicting young adults, was diagnosed in an 81-year-old woman. Treatment was started with orally administered antibiotics but was soon halted because of side effects. She was treated instead by local spread of a 3% rifampin ointment. After 6 weeks, the lesion cleared up and she improved remarkably. There was no recurrence during 18 months of follow-up. The current report is the second published case of rhinoscleroma in an elderly person and the first report on its cure by local treatment with a 3% rifampin ointment. This favorable experience contributes to the limited knowledge on rhinoscleroma in the elderly.

[Cutaneous larva migrans].

Larva migrans is a rare cutaneous parasitic infestation, whose incidence in Israel has increased over the past few years. This is mainly due to the growing number of Israelis traveling to the Far East and to Central and South America. We present 4 such cases. The treatment of choice for this parasite is thiabendazole, an imidazole with anthelminthic properties.

Reactive perforating collagenosis.

Seven patients with reacting perforating collagenosis (RPC) were diagnosed from 1974 to 1982. Experimental production of lesions in two patients confirmed the contributory role of superficial trauma. The pathogenesis of RPC involves transepithelial elimination of altered collagenous bundles. This process may be observed in a wide variety of disparate skin diseases.

Pityriasis rotunda in a white patient. Report of the second case and review of the literature.

A 19-year-old white woman with pityriasis rotunda in whom no diagnosable disorder could be demonstrated is reported on herein. Pityriasis rotunda has been described in Oriental and black patients, usually in association with certain serious systemic diseases. Our patient appeared to have the second reported case of pityriasis rotunda in white persons. In both cases the dermatosis occurred in an otherwise healthy individual. Physicians should be alert to the possible occurrence of pityriasis rotunda in white patients. The literature on pityriasis rotunda is reviewed.

Effects of Solcoderm.

The effects of treatment and depths of penetration of a 5-fluorouracil and salicylic acid preparation (Solcoderm) were studied in 24 patients treated for basal cell carcinoma with this compound. Two thirds of the patients in our study showed islands of residual tumor in the dermis following treatment, whereas total disappearance of the tumor was observed in one third. The depth of the fibrotic changes induced by the drug varied from 0.34 to 0.40 cm for the morphea type of basal cell carcinoma and from 0.52 to 0.88 cm for the conventional types. It is recommended that treatment with this compound be reserved only for superficial basal cell carcinomas and that it be avoided altogether in basal cell carcinomas of the morphea type.