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J Breeding

Publications and source records attributed to J Breeding.

13 recordsLinked to original sources

Coal tar phototherapy for psoriasis reevaluated: erythemogenic versus suberythemogenic ultraviolet with a tar extract in oil and crude coal tar.

Recent studies have questioned the therapeutic value of coal tar versus ultraviolet (UV) radiation and their relative necessity in phototherapy for psoriasis. In this investigation, different aspects of tar phototherapy have been studied in single-blind bilateral paired comparison studies. The effects of 1% crude coal tar were compared with those of petrolatum in conjunction with erythemogenic and suberythemogenic doses of ultraviolet light (UVB) using a FS72 sunlamp tubed cabinet. Crude coal tar was clinically superior to petrolatum with suberythemogenic ultraviolet. With the erythemogenic UVB, petrolatum was equal in efficacy to crude coal tar. Suberythemogenic UVB was also used adjunctively to compare the effects of a 5% concentration of a tar extract in an oil base to 5% crude coal tar in petrolatum or the oil base without tar. The tar extract in oil plus suberythemogenic UVB produced significantly more rapid improvement than the oil base plus UVB. The direct bilateral comparison of equal concentrations of tar extract in oil base versus crude coal tar in petrolatum in a suberythemogenic UV photo regimen revealed no statistical differences between treatments. In a study comparing tar extract in oil and the oil base without ultraviolet radiation, the tar extract in oil side responded more rapidly. This demonstrates a direct effect of tar alone in therapy. We have also studied the effects of erythemogenic and suberythemogenic UVB with and without tar extract in oil in the hairless mouse epidermal deoxyribonucleic acid (DNA) synthesis suppression assay. It was found that erythemogenic dosages of UVB produced near maximal inhibition of DNA synthesis with or without coal tars. Suberythemogenic dosages of UVB produced submaximal suppression of DNA synthesis that was enhanced by adjunctive coal tar but not by vehicle, findings which are consistent with the above clinical results. These studies suggest that coal tars combined with suberythemogenic UVB therapy is a practical alternative (to more aggressive UVB therapy without coal tar) which reduces the UVB exposure to the patient.

Animals↗

Etretinate treatment for psoriasis inhibits epidermal ornithine decarboxylase.

Previous studies of the polyamines and their biosynthetic enzyme ornithine decarboxylase (ODC) in psoriatic skin have revealed several abnormalities, including significantly elevated ODC activity. Retinoids have also been shown to modulate polyamine biosynthesis and inhibit ODC activity after different stimuli in various cell and tissue systems. The effect of etretinate has been studied on ODC activity in involved and uninvolved psoriasis skin. Increased ODC activity was found in pretreatment samples from both involved and uninvolved psoriatic skin compared with normal volunteers. Etretinate treatment significantly reduced ODC activity in both involved and uninvolved skin in psoriatics to a similar level of activity before any improvement in clinical appearance was noted. Inhibition of epidermal ODC activity in psoriasis may represent one mechanism of retinoid action on the abnormal skin psoriasis.

Carboxy-Lyases↗

Retinoic acid modulation of ultraviolet light-induced epidermal ornithine decarboxylase activity.

Irradiation of skin with ultraviolet light of sunburn range (UVB) leads to a large and rapid induction of the polyamine biosynthetic enzyme ornithine decarboxylase in the epidermis. Induction of epidermal ornithine decarboxylase also occurs following application of the tumor promoting agent 12-0-tetradecanoylphorbol-13 acetate and topical retinoic acid is able to block both this ornithine decarboxylase induction and skin tumor promotion. In the studies described below, topical application of retinoic acid to hairless mouse skin leads to a significant inhibition of UVB-induced epidermal ornithine decarboxylase activity. The degree of this inhibition was dependent on the dose, timing, and frequency of the application of retinoic acid. To show significant inhibition of UVB-induced ornithine decarboxylase the retinoic acid had to be applied within 5 hr of UVB irradiation. If retinoic acid treatment was delayed beyond 7 hr following UVB, then no inhibition of UVB-induced ornithine decarboxylase was observed. The quantities of retinoic acid used (1.7 nmol and 3.4 nmol) have been shown effective at inhibiting 12-0-tetradecanoyl phorbol-13 acetate induced ornithine decarboxylase. The results show that these concentrations of topical retinoic acid applied either before or immediately following UVB irradiation reduces the UVB induction of epidermal ornithine decarboxylase. The effect of retinoic acid in these regimens on UVB-induced skin carcinogenesis is currently under study.

Animals↗

Cutaneous polyamines in psoriasis.

The polyamines putrescine, spermidine and spermine are intimately associated with cellular growth and division. Previous studies of the polyamines and their rate limiting biosynthetic enzyme, ornithine decarboxylase, in psoriasis have shown significant changes compared with non-psoriatic skin. We have further studied cutaneous polyamines in patients with psoriasis and in normal subjects, epidermal shave biopsies were taken and assayed for ornithine decarboxylase activity and polyamine levels. Psoriasis lesions showed increased ornithine decarboxylase activity compared with uninvolved skin. The levels of ornithine decarboxylase activity in uninvolved psoriasis skin were also higher than in normals. There was increased putrescine in involved psoriasis compared with uninvolved and normal skin. Spermidine and spermine were increased in psoriasis skin and in uninvolved skin and compared with normals. The spermidine/spermine ratio was greatest in involved skin compared with uninvolved and normal. These results confirm abnormal polyamine metabolism in both the involved and uninvolved skin of psoriatics.

Humans↗

Inhibition of ultraviolet-B epidermal ornithine decarboxylase induction and skin carcinogenesis in hairless mice by topical indomethacin and triamcinolone acetonide.

Modulation of ultraviolet-B (UVB) skin carcinogenesis by topical treatment with two antiinflammatory drugs expected to have different mechanisms of action has been studied in the hairless mouse. Indomethacin is a nonsteroidal antiinflammatory agent which may act by inhibiting prostaglandin biosynthesis. Triamcinolone acetonide is a steroidal antiinflammatory agent. Both of these drugs inhibited the induction of epidermal ornithine decarboxylase by UVB when applied topically in a acetone vehicle. A UVB skin tumor study was designed. Groups of mice were irradiated daily with UVB for 20 days, each mouse receiving a total of 17.1 kJ UVB per sq m. Group 1 was treated with acetone immediately after each irradiation; Group 2 received 700 nmol indomethacin in acetone immediately after each irradiation; Group 3 received 14.4 nmol triamcinolone acetonide in acetone immediately after each irradiation. Mice were killed after 52 weeks, and the tumors were excised and examined histologically. Both topical indomethacin and topical triamcinolone acetonide were effective in reducing the incidence and size of the skin tumors induced by UVB. This evidence supports the hypothesis that the induction of ornithine decarboxylase may be a critical component of UVB skin carcinogenesis and that inhibition of ornithine decarboxylase induction can be used as a screen for agents which will inhibit UVB skin carcinogenesis.

Animals↗

Psoriasiform dermatosis in a rhesus monkey. Epidermal labeling indexes, polyamines, and histopathologic findings.

We have previously described the clinical and dermatopathologic features of a psoriasiform dermatosis in a rhesus monkey (Macaca mulatta). This animal has been studied further in attempts to characterize its skin disease. Epidermal cell DNA synthesis was measured following the intradermal injection of tritiated thymidine. Epidermal cell labeling indexes in the involved and uninvolved skin of the affected monkey and in the skin of a normal monkey were compared. The labeling indexes in the involved skin were significantly increased as compared with uninvolved skin; they were also significantly higher than in normal skin. Epidermal polyamine assays showed increased epidermal putrescine in involved skin together with increased spermidine and an increased spermidine-spermine ratio compared with uninvolved and normal skin sites.

Animals↗

Anthralin. Different concentration effects on epidermal cell DNA synthesis rates in mice and clinical responses in human psoriasis.

There had been recent interest in psoriasis treatment regimens with low anthralin concentrations of 0.01% and 0.05%. These regimens used salicylic acid, coal emollient baths, and ultraviolet energy. We were interested in evaluating the effects of different concentrations of anthralin without adjunctive therapy. We studied the effects of anthralin on epidermal cell DNA synthesis in hairless mice and found that, in concentrations between 0.1% and 0.4%, anthralin produced significant suppression. However, 0.05%, 0.025%,and 0.01% anthralin failed to inhibit DNA synthesis. Clinical studies of 0.05% and 0.1% anthralin in a water-in-soil emulsion (Eucerin) were performed on 14 patients with psoriasis. Psoriasis severity was scored before and during the period of anthralin use and showed a significant improvement in 0.1% anthralin-treated sites. No significant differences were noted between 0.05% anthralin-treated areas and those areas treated with the vehicle alone.

Adolescent↗

Psoriasiform dermatosis in a rhesus monkey.

We describe a dermatosis in a rhesus monkey (Macaca mulatta) that has the characteristic features of the human skin disease, psoriasis vulgaris. The monkey was affected by chronic erythematous, scaling plaques that occurred on the scalp, face, dorsal back, the extensor aspects of the limbs and the palms and soles. Subungual hyperkeratosis was present. Skin biopsies of the affected skin showed a regular acanthosis with reduction of granular cell layer, parakeratosis and supra papillary thinning of the epidermis. Foci of inflammatory cells were seen in the upper epidermis. The dermal changes were tortuous capillary loops and benign inflammatory infiltrate, particularly in the papillary dermis, all of which are features of the human skin disease psoriasis vulgaris. The presence of a nutritional deficiency syndrome was excluded and there was no evidence of any systemic disease.

Animals↗

Evaluation of sunscreen protection by measurement of epidermal DNA synthesis.

Different sunscreens were tested to determine their protection of epidermis from ultraviolet light effects. Ultraviolet light-induced changes in hairless mouse epidermal DNA synthesis were used for measurement of sunscreen protection. Visual assessment of erythema and edema was also performed. This initial study has evaluated sunscreens containing para-aminobenzoic acid (PABA) as the principle sunscreen chemical. These experiments were conducted using fluorescent sunlamp tubes and hydroxylapatite extraction of epidermal DNA. The ultraviolet light exposure was measured using a recording radiometer. The results showed that the sunscreens tested were able to partially prevent ultraviolet light induced changes in epidermal DNA synthesis. It may be possible to use this assay as one of the initial evaluations of potential ultraviolet light protectants.

4-Aminobenzoic Acid↗

Antiinflammatory drug effects on ultraviolet light-induced epidermal ornithine decarboxylase and DNA synthesis.

Ornithine decarboxylase which forms putrescine by the decarboxyalation of ornithine, is the first and probably the rate-limiting enzyme in the biosynthesis of the other polyamines, spermidine and spermine. Epidermal ornithine decarboxylase activity is greatly elevated in response to tumor promoting agents and ultraviolet light. The purpose of this paper is to report modification of ultraviolet-induced epidermal ornithine decarboxylase activity by antiinflammatory agents. Topical triamcinolone acetonide and indomethacin were found to significantly inhibit the UV-B induction of epidermal ornithine decarboxylase in hairless mice when applied following ultraviolet light irradiation. The corticosteroid also showed inhibition of ultraviolet light increased epidermal DNA synthesis. Indomethacin failed to show any inhibition of DNA synthesis. It is suggested that these assays may be used to study drugs that may modulate some ultraviolet light effects on the epidermis.

Animals↗

The ethics of informed parental consent to psychiatric drugging of children.

That so many children are taking prescribed psychiatric drugs means that millions of parents have agreed to this recommendation for their children. Most pertinent to this fact is the question whether these parents have been given the opportunity to make their decisions in accordance with the legal standard of informed consent which requires a physician to disclose sufficient information for a patient to make an "informed" decision about a proposed treatment. At the least, such legitimate consent entails an opportunity to evaluate knowledgeably the options available and the risks attendant upon each, without coercion. This article examines the ethics of informed consent in psychiatry, and extant practices in the field, especially in regard to the psychiatric drugging of school age children in the United States. The authors argue that informed consent is systematically violated in this domain, and present a look at what authentic informed consent for parents to decide about psychiatric drugs for their children would entail.

Attention Deficit Disorder with Hyperactivity↗