Comparison of croton oil and benzoyl peroxide on DNA synthesis in ultraviolet-irradiated skin.
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Animals↗
Biomedical subjects
J H Epstein
Publications and source records attributed to J H Epstein.
All-trans-retinoic acid and cutaneous cancers.
All-trans-retinoic acid (tretinoin) is a biologically active metabolite of vitamin A. Topical tretinoin has been shown to have antineoplastic activity in a variety of experimentally induced and naturally occurring tumors. In some animal studies it has inhibited the development of ultraviolet-induced carcinomas. However, in other studies it accelerated such ultraviolet tumorigenesis. Other work has shown that the drug can eradicate chemically induced papillomas and carcinomas. These various effects may stem from tretinoin's influences on deoxyribonucleic acid synthesis, polyamine enzyme systems, sister-chromatid exchanges, oncogene expression, or lysosome lability. In clinical trials, tretinoin removed premalignant actinic keratoses from the face. Combined with 5-fluorouracil, it is also quite effective in the treatment of such lesions on the forearms and hands, areas where neither agent alone has much effect. It should be emphasized that tretinoin has not been shown to be carcinogenic in either animals or humans. After more than a decade of topical use of tretinoin on human skin, there is no evidence that the drug either initiates or promotes carcinogenesis in humans.
Animals↗
Polyarticular septic arthritis.
Seven adult patients with nongonococcal polyarticular septic arthritis are presented with a literature review of the clinical features of polyarticular bacterial infection. Polyarticular septic arthritis occurred in 19% of reported cases of septic arthritis in adults. Similar to monoarticular disease, the knee was the most commonly affected joint, and Staphylococcus aureus was the most frequently isolated microorganism. Pneumococcus, group G streptococcus, and Hemophilus influenzae had an increased association with polyarticular infection. Five of our 7 patients had underlying rheumatic diseases and the immediate mortality rate was 57%. Review of the literature yielded an overall mortality of 23% for polyarticular septic arthritis compared to the 9% mortality of septic arthritis in general. The subset of patients with polyarticular infection superimposed on rheumatoid arthritis had a mortality rate of 56%.
Aged↗
American dermatology training programs and the foreign medical graduate from less-advantaged geographical areas.
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Dermatology↗
Polymorphous light eruption.
The polymorphous light eruptions are idiopathic photodermatoses characterized by various clinical patterns ranging from small papules and papulovesicular lesions to large papules that coalesce to form plaques. The eruptions may begin at any time of life from young childhood to old age, and any race may be afflicted. However, they are particularly prevalent in the North American and Latin American Indian and the Finnish populations. In these two populations there appears to be a genetic (dominant) predisposition to develop the problem. The results of phototesting procedures indicate that the UVB rays make up the action spectrum for reproducing the lesions. However, some patients react to UVA wavelengths as well, and two reports suggest that certain patient populations will react abnormally only to UVA rays. The mechanism of the response is unclear, although the clinical picture, delayed reaction time, and histology suggest that at least some of these responses are due to a cell-mediated hypersensitivity reactivity. Therapy varies with degrees of sensitivity. Protection with clothes, strong sunscreens, and avoidance of the noonday sun may be essential for exquisitely sensitive patients. Topical and systemic corticosteroids may be needed for acute exacerbations. Systemically the 4-aminoquinoline antimalarial drugs are quite effective for less sensitive patients with the large papule and plaque variety. Thalidomide has proved to be most effective in the American Indian form of the disease, and PUVA has been found to be most effective in treating and preventing the process in even very sensitive patients. Most recently, the systemic use of Imuran has proved to be of great value in middle- to older-aged individuals with a severe eczematous form of the disease.
Dermatitis, Contact↗
Guanadrel. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in hypertension.
Guanadrel sulphate is an orally active peripheral sympathetic inhibitor (adrenergic neuron-blocking drug). In comparative studies, guanadrel was comparable in efficacy with guanethidine or methyldopa in mild to moderately severe hypertension, although generally it caused fewer central nervous system side effects than methyldopa and less orthostatic dizziness and diarrhoea than guanethidine. However, its efficacy in patients whose blood pressure remains inadequately controlled by other drugs (except diuretics alone) has yet to be adequately demonstrated. Guanadrel has a rapid onset of action and a half-life of about 10 hours, thus dose titration can be achieved more rapidly than with guanethidine, and twice daily administration is appropriate. Generally, guanadrel has been well tolerated, withdrawal of treatment due to adverse effects seldom being necessary. Thus, guanadrel appears to be a suitable alternative to methyldopa for the treatment of mild to moderately severe hypertension not controlled adequately by diuretics alone.
Antihypertensive Agents↗
Nitrogen mustard (mechlorethamine) and UVB photocarcinogenesis: a dose response effect.
The effects of UVB energy and nitrogen mustard (mechlorethamine, HN2) on tumor formation in the hairless mouse skin was examined. Twice weekly applications of HN2 produced tumors in 34% of the mice. In addition, the HN2 treatments plus UVB radiation resulted in a significant acceleration in tumor formation as compared to either carcinogenic stimulus alone. The twice weekly application of HN2 plus UVB exposure was more tumorigenic than UVB plus HN2 applied once a week. Thus a positive carcinogenic dose response was noted. No tumor-suppressing effects were detected in this study.
Animals↗
A study of the effect of chronic applications of nitrogen mustard (HN2) on acute responses of mammalian skin to UVB irradiation in vivo.
The effect of chronic applications of HN2 on acute responses of DNA synthesis to UVB radiation was studied in Uscd strain hairless mouse skin in vivo. 0.1 mg of HN2 in 95% ethyl alcohol and the diluent were applied weekly to the backs of the mice for 69 wk. The mice were then exposed to 1.98 X 10(2) J/m2 of UVB energy and were sacrified 4 hours and 48 h post-irradiation. The effects on DNA synthesis were evaluated using TdRH3 as the radioactive tracer. The results of the study revealed that the chronic HN2 applications increased the number of basal cells in the DNA synthesis phase of the mitotic cycle. This was associated with acanthosis and cellular hypertrophy. 4 h post-irradiation there was the expected depression in DNA synthesis in both the HN2- and diluent-treated mice. In addition, 48 h post-irradiation the number of basal cells synthesizing DNA was accelerated in both the HN2- and diluent-treated mice. However, it was much more noticeable in the HN2-treated animals. Whether this increased activity is related to the additive carcinogenesis generated between UVB and HN2 remains to be determined.
Animals↗
Effects of mechlorethamine (HN2, nitrogen mustard) on UV-induced carcinogenesis in hairless mouse skin.
The influence of mechlorethamine (HN2, nitrogen mustard) on UV-induced carcinogenesis was examined in the hairless mouse skin in vivo. Noncarcinogenic amounts of topically applied HN2 and carcinogenic levels of UVB energy were used in the study. The HN2 applications significantly accelerated the appearance and growth of cutaneous tumors in this study. Thus HN2 acted as either a promoter or cocarcinogen for UV-induced cancer formation. Although the mechanism of this effect was not established, combinations of UVB radiation and HN2 topical therapy pointed to an increased incidence of cutaneous tumors in human skin.
Animals↗
Phototoxicity and photoallergy in man.
Photosensitivity is the broad term used to denote adverse reactions to the sun. These reactions may be phototoxic or photoallergic. Phototoxic reactions are much more common than photoallergic reactions. Phototoxic reactions may be photodynamic or nonphotodynamic in nature, the primary difference being that photodynamic reactions require oxygen. Porphyrins are examples of molecules which produce photodynamic responses. The 8-methoxypsoralen photobinding to DNA is an example of a nonphotodynamic reaction. The UVB sunburn response is the most common phototoxic reaction, and it appears to be nonphotodynamic in nature. Photoallergy is uncommon. As with all allergies it is an acquired, altered reactivity dependent on an antigen-antibody or cell-mediated hypersensitivity response. Solar urticaria due to UVB rays is an example of a circulating antibody-dependent reaction, and allergic photocontact dermatitis induced by the halogenated salicylanilides is an example of a cell-mediated response. The mechanisms of these reactions are discussed.
Acute Disease↗
Photocarcinogenesis, skin cancer, and aging.
Nonmelanoma skin cancers, like most malignancies, increase in incidence with increasing age. However, in general they are not due to the aging process but are primarily due to solar radiation. Clinically, squamous cell carcinomas and basal cell epitheliomas are the most common cancers that occur in the Caucasian population in the United States. The role of radiation from the sun was suggested by a number of astute clinical observations reported around 1900 and subsequently has been established by epidemiologic and experimental studies. Action spectrum evaluations indicate that the ultraviolet B (UVB) rays are the most carcinogenic. However, recent studies indicate that the UVA rays can augment the cancer-producing effects of UVB rays. Other physical stimuli, including heat and wind, can also accelerate UVB carcinogenesis. Chemicals such as the polycyclic hydrocarbons, the nitrosoureas, and nitrogen mustard have an additive carcinogenic effect with UVB radiation. Also, some chemicals such as croton oil, the phorbol ester--TPA, and all-trans-retinoic (RA) acid can promote UVB-initiated carcinogenesis. RA can also inhibit UVB-induced cancer formation. The role of the immune status has received a great deal of attention. Both in experimental and clinical situations, nonspecific immune suppression results in increased cancer formation. Also, recent studies indicate that a specific T cell suppressor population can be induced in experimental animals with UVB which will inhibit rejection of tumors produced by UVB radiation. Finally, damage to DNA by UVB radiation is well established. Studies with the genetic disease xeroderma pigmentosum support the concept that such damage, if not repaired, will lead to cancer formation. It also has been suggested that unrepaired damage to deoxyribonucleic (DNA) and other macromolecules is at least in part responsible for the aging process in general.
Aging↗
Autoradiographic study of colchicine inhibition of DNA synthesis and cell migration in hairless mouse epidermis in vivo.
In vivo effects of colchicine on mitotic counts, DNA synthesis, and cell migration time were investigated in hairless mouse epidermis. [H3]TdR was used to examine DNA synthesis and measure the transit time. We found that colchicine (at a dose of 50 micrograms/25 g body weight) caused mitotic arrest, but had no effect on the number of cells in S phase during the first 4 hr after injection. Colchicine reduced the number of cells in S phase in normal epidermis during the 16-30 hr after injection, but the effect was no longer seen at 42 hr post injection. A similar depression in S-phase cell counts appeared in UVR-stimulated hyperplastic epidermis by 48 hr after injection of colchicine. In addition, migration of [H3]TdR-labelled cells from the basal layer to the superficial layers in UVR-stimulated hyperplastic epidermis was disturbed by colchicine injection. The delay in movement was not seen during the first 24 hr, but appeared by 48 hr after injection.
Animals↗
Cost-effectiveness of PUVA therapy: Further considerations.
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Cost-Benefit Analysis↗
Ultrastructural demonstration of chemical modification of melanogenesis in hairless mouse skin.
We investigated chemical and physical modifications of the genetically determined ultrastructure of melanosomes. The flank skin of hairless mice was treated with ultraviolet energy (UV) shorter than 320 nm or with a combination of a photosensitizer and UV (PUVA treatment). All melanosomes in the induced melanocytes and those in resident melanocytes in the ear skin showed eumelanogenesis, although the degree of melanin deposition differed considerably according to the induction process. Eumelanogenesis was most advanced in the resident melanocytes while PUVA-induced melanocytes showed more immature premelanosomes. We then topically applied 4-tertiary butyl catechol on the skin. The depigmenting agent caused an appearance of pheomelanosomes. The alteration in melanogenesis was seen most distinctly in premelanosomes of the PUVA-induced cells. Altered ultrastructure was also observed in matured melanosomes; this change was most apparent in the resident melanocytes. These findings indicate that cells with eumelanogenesis may undergo pheomelanogenesis. The present study demonstrated effects of chemicals on genetically determined function of melanocytes by quantitative analysis of melanosome ultrastructure.
Animals↗
Strategies to promote direct access: the public education alternative.
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Cost-Benefit Analysis↗
Chemical phototoxicity in humans.
Phototoxic reactions may be induced by endogenous or exogenous chemicals. Endogenous photosensitizers made by the body include porphyrin molecules which are responsible for the photocutaneous syndromes noted in the porphyrias. Exogenous photosensitizers may arrive on the skin through topical applications or may be distributed through the vasculature. Topical photosensitizers are found in cosmetics, medications, plants, and industrial and air pollutant emissions. Systemic photosensitizers consist primarily of therapeutic agents. Acute and chronic phototoxic reactions may occur. The acute response is generally characterized by erythema and edema followed by hyperpigmentation and desquamation. The end point of chronic damage may be cutaneous cancer formation. The mechanisms of these changes may well relate to nucleic acid injury, protein and membrane damage, and alterations in other nuclear and cytoplasmic molecular structures. However, translation of experimental information into human responses remains to be clarified. A great deal of investigation is still needed in developing assays for detecting phototoxic chemicals and for defining mechanisms involved in phototoxic events in human skin.
Drug-Related Side Effects and Adverse Reactions↗
Suntan salons and the American skin.
Suntan salon franchises burst upon the economic scene in the United States in 1978 and proliferated rapidly. At present it is estimated that between 1,000 and 2,000 salons are active in the country. Of the two types in use, the more common uses a fluorescent UVB source which emits primarily the highly injurious sunburn rays between 290 and 320 nm. These are the rays that not only are responsible for the acute cellular injury and erythema called "sunburn," but at least under experimental conditions are the most carcinogenic. The UVA units are found primarily in Europe. The hazards of their rays have not been clarified as yet, but they are known to be responsible for the vast majority of exogenously photosensitized reactions that occur in the skin, they do augment the acute injury produced by the UVB rays, they cause dermal blood vessel damage, and they can produce lenticular injury. In conclusion, tanning for cosmetic purposes is not innocuous.
Advertising↗
Effects of retinoids on ultraviolet-induced carcinogenesis.
The evidence for effects of the retinoids on UV-induced carcinogenesis is sparse. Clinical observations indicate that topical RA can cause significant regression of premalignant actinic keratoses. Also there is some evidence that this agent can cause dissolution of some basal cell epitheliomas. However this latter effect does not appear to be of therapeutic value. Systemic retinoids are of little value in the treatment of premalignant and malignant cutaneous lesions though 13-cis-retinoic acid might be of use in the basal cell nevus syndrome. Examination of the influence of the retinoids on photocarcinogenesis essentially has been confined to RA and animal experimentation. RA in nontoxic concentrations can both stimulate and inhibit photocarcinogenesis depending upon the circumstances of the study. The mechanisms of these responses are not clear. Influences on DNA synthesis directly and/or indirectly or on immune responses may be involved in both effects. Preliminary studies with oral 13-cis-retinoic acid have not demonstrated any effects to date on UV-induced skin cancer formation.
Animals↗