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Biomedical subjects

R Roelandts

Publications and source records attributed to R Roelandts.

44 records · Page 3Linked to original sources

Mutagenicity and carcinogenicity of methoxsalen plus UV-A.

The combination of methoxsalen and long-wave UV radiation (UV-A) is being used on a large scale in clinical practice to treat a variety of dermatoses, particularly psoriasis. Theoretically, this combination may be mutagenic and carcinogenic, since methoxsalen binds covalently with DNA under the influence of UV-A. Mutagenicity has been studied in microorganisms and cell cultures. Arguments for possible carcinogenicity come from animal experiments and also from long-term follow-up studies of patients treated with psoralens and UV-A (PUVA). Transplantation studies in animals, allergic and irritative skin reaction experiments, and clinical observations indicate that PUVA also has an immunosuppressive effect. Short-term risk of skin cancer from PUVA therapy seems to be rather low if careful patient selection is made. However, for all patients, long-term maintenance treatment should be avoided as much as possible.

Animals↗

Skin determination of the 8-methoxypsoralen concentration in rats.

This paper describes a method for determining the amount of 8-methoxypsoralen in rat skin tissue by means of high performance liquid chromatography. The 8-methoxypsoralen was extracted with an organic solvent out of homogenized skin tissue. Following evaporation of the solvent, the extracts could be injected directly into the column without further purification. The procedure is relatively simple.

Animals↗

The relationship between 8-methoxypsoralen skin and blood levels.

A method is described to determine the 8-methoxypsoralen (8-MOP) concentration in vivo in the skin by means of high-performance liquid chromatography (HPLC). Skin and blood samples were taken from 80 rats at specific intervals after oral administration of [3H]8-MOP. The pharmacokinetic results obtained for the skin levels were compared to the blood levels. In addition, liquid scintillation counting (LSC) was done on all the samples to compare the concentrations of 8-MOP plus metabolites to the concentrations of 8-MOP alone. There was a good correlation between the 8-MOP skin and blood levels. The values obtained with LSC were higher in function of time than the corresponding values obtained by HPLC, which indicates the presence of metabolites in both the skin and the blood. No statistically significant difference in the time of peaking was noted for the skin and blood levels. The blood levels seem to be a good parameter for the 8-MOP skin concentration.

Administration, Oral↗

Dietary influences on 8-MOP plasma levels in PUVA patients with psoriasis.

To study the effect of diet on 8-MOP plasma levels, these levels were measured three times in twenty PUVA patients with psoriasis; while fasting, after a low-fat breakfast, and after a fat-rich breakfast. No significant differences were found between the maximal 8-MOP plasma levels in the fasting condition and the levels after the low-fat breakfast, both peaking 2 h after ingestion. After the fat-rich breakfast, however, the 8-MOP plasma levels were not only significantly lower at 2 h but also peaked later, reaching their maximum at 3-4 h after intake. The drug should therefore be given in a dietetically standardized way. This raises the question whether some cases of therapy resistance can be dietetically influenced.

Diet↗

Skin photosensitization with topical hypericin in hairless mice.

Hypericin, a naturally occurring photosensitizer, exhibits interesting in vitro photobiological activities, which suggest that the compound is a potential antipsoriatic agent. In this study, the possibility of hypericin penetrating the skin in photo-active concentrations has been studied. Hypericin is incorporated in either emulsifying ointment supplemented with solketal (hypericin content: 0.05%) or in polyethylene glycol (PEG) ointment (hypericin content: 0.5%) and applied to the skin of hairless mice for 4 h. After removing excess ointment, the mice are then irradiated with different light doses using a 500 W halogen lamp. As a positive control, intraperitoneally (i.p.) administered hypericin (10 and 40 mg/kg) has also been tested. Erythema, desquamation and erosions are demonstrated in the mice treated with hypericin in emulsifying ointment with solketal using a light dose of at least 4.5 J/cm2. In general, these reactions correlate well with those of i.p. administered hypericin (40 mg/kg), indicating that hypericin incorporated in emulsifying ointment with solketal is well absorbed by the skin of the mice. However, for the i.p. administered hypericin (40 mg/kg), we could not evaluate phototoxic reactions in the group of animals that received a light dose of 108 J/cm2, as they all died 12-24 h after irradiation, indicating extreme photosensitization with systemic hypericin at higher light doses. On the contrary, there is no measurable skin photosensitivity induced by hypericin when incorporated in PEG ointment or when 10 mg/kg hypericin is i.p. administered. Our results show that hypericin incorporated in a suitable vehicle can be delivered to the skin in photo-active concentrations. Using a vehicle such as emulsifying ointment with solketal, it will be possible to explore the photo-activity of hypericin in the treatment of psoriasis and other skin diseases.

Administration, Topical↗