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Biomedical subjects

N J Lowe

Publications and source records attributed to N J Lowe.

At least 109 records · Page 6Linked to original sources
PubMed1986

A comparative study of the induction of epidermal hyperplasia by natural and synthetic retinoids.

Retinoids are potent inducers of epidermal hyperplasia. In the present study the ability to induce epidermal hyperplasia by a variety of retinoids has been compared. Thirteen retinoids and beta-carotene were applied topically in an acetone vehicle to the dorsal skin of hairless mice and the dose-response and time course for the induction of hyperplasia were measured. Peak hyperplasia occurred 4 to 5 days after a single topical dose, and was induced by doses well below those producing gross or histological signs of cutaneous toxicity. The induction of hyperplasia was dose-dependent, the number of epidermal cell layers increasing initially in proportion to the log of the dose and then tending to plateau or, in some cases decrease, after which further increases in dose were associated with the appearance of gross and histological toxicity. The slopes of the initial increasing phase were determined and potencies expressed as the dose producing a 50% increase in the number of epidermal cell layers. All-trans-retinoic acid and its analogs, etretinate and its free acid, (E)-4[2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl- 2-naphthalenyl)-1-propenyl]-benzoic acid (arotinoid) derivatives, retinol and retinal produced an increase in the number of cell layers proportionate to the log of the dose. Decarboxylated (E)-4[2-(5,6,7,8-tetrahydro-5,5,8,8- -tetramethyl-2-naphthalenyl-1-propenyl]-benzoic acid, a cis-locked aryl triene derivative of retinoic acid and beta-carotene were inactive. Similar time courses were observed when retinoids were dosed p.o. The relative potencies of the retinoids in this system show similar trends to those reported for biological activities measured in other in vivo and in vitro assays.

Animals↗
PubMed1985

Pharmacokinetics of topically applied radiolabeled retinoids in hairless mouse epidermis and dermis after single applications.

The retention of tritium-labeled all-trans-retinoic acid (RA), 13-cis-retinoic acid (13-cis-RA), aromatic retinoid, and arotinoid ethyl ester in the epidermis and dermis of hairless mice was measured up to 24 h following a single topical application in an acetone vehicle. The radioactivity in the tissues was extractable with chloroform:methanol, and the identities of the radioactive species extracted were confirmed as retinoids using thin-layer chromatography. All the retinoids were absorbed into the skin rapidly. After an initial period of distribution and penetration (lasting for about 1 h) the amount of the applied retinoid remaining in the epidermis and dermis decreased more slowly, obeying first order (exponential) decay kinetics. Both the arotinoid and the aromatic retinoid persisted for longer in the epidermis than equivalent doses of RA or 13-cis-RA. The half-lives of the retinoids in the dermis tended to be longer than in the epidermis, except for the arotinoid. Aromatic retinoid persisted for longest in the dermis with a half-life of 11 h.

Administration, Topical↗
PubMed1985

Isotretinoin vs etretinate therapy in generalized pustular and chronic psoriasis.

The clinical response to isotretinoin (13-cis-retinoic acid) in 11 patients with generalized pustular psoriasis was evaluated. Control of pustulation and systemic symptoms was achieved in ten cases, but additional therapy was required to produce complete clearing of all psoriatic lesions. Also, the efficacy of isotretinoin and etretinate in the treatment of chronic plaque psoriasis was compared in 29 patients. Isotretinoin was found to be less effective than etretinate in the treatment of chronic plaque psoriasis.

Adult↗
PubMed1984

Psoriasis.

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Adolescent↗
PubMed1984

Anthralin for psoriasis: short-contact anthralin therapy compared with topical steroid and conventional anthralin.

Anthralin is an effective topical drug for psoriasis therapy. Recent studies have suggested that anthralin may be effective in high concentrations for short periods of skin contact. The purpose of these studies was to compare psoriasis improvement rates in patients treated with 0.3% anthralin ointment for 10 minutes' skin contact daily with patients treated with a topical steroid, difluorosone diacetate. A further study conducted was a bilateral paired comparison between conventional strength (0.1%-0.5%) anthralin ointment overnight with high concentration anthralin (0.5%-3%) for short contact periods of 10 minutes daily. The results showed good responses in all treatment groups. Short-contact anthralin is confirmed as a practical means of outpatient therapy for psoriasis.

Administration, Topical↗
PubMed1984

Ultraviolet radiation-induced connective tissue changes in the skin of hairless mice.

Hairless mice (Skh/ hr1 ) were exposed to ultraviolet A (UVA; peak irradiance at 365 nm), or to ultraviolet B (UVB; peak irradiance at 313 nm) radiation. The animals received 12 treatments on alternate days. Connective tissue changes in the skin were monitored by assaying hydroxyproline and desmosine as an indication of collagen and elastin concentrations, respectively. The activities of prolyl hydroxylase and collagen glucosyl-transferase, enzymes participating in the biosynthesis of collagen, were also assayed. The concentration of elastin was significantly increased in mice treated with UVA or UVB. The concentration of collagen was unaffected by the treatments, but the activity of prolyl hydroxylase, reflecting collagen synthetic capacity, was decreased in UVA-treated mice. The collagen glucosyl-transferase activity was unchanged. Irradiation of purified human prolyl hydroxylase with UVA in vitro decreased the enzyme activity at higher doses, but UVB had no effect. The results indicate that definitive changes in the biochemistry of dermal connective tissues can be induced by exposure of mice to UV irradiation.

Animals↗
PubMed1984

Histologic changes in the skin of the rhino mouse (hrrhhrrh) induced by retinoids.

The effects of four retinoids, all-trans-retinoic acid (RA), 13-cis-retinoic acid (13-cis-RA), aromatic retinoid, and arotinoid ethyl ester ( arotinoid ) were examined on the skin of the rhino mouse. Rhino mouse skin is characterized by the presence of keratin-containing utricles attached to the epidermis, and subcutaneous cysts, both of which are derived from hair follicles. The utricles were examined in horizontal sheets of epidermis, and in vertical histologic sections. After applications of 0.1 ml of 0.1% RA, 0.1% 13-cis-RA, 0.1% aromatic retinoid, or 0.001% arotinoid in acetone to the dorsal skin for 5 days a week for 2 weeks, there was a reduction of utricle diameter to 45%, 52%, 30%, and 31% of acetone-treated controls, respectively. Histologic examination of the epidermis revealed that a dose-dependent hyperplasia and thickening of the epidermis and the stratum granulosum was induced by the retinoids when given at subtoxic doses, being most marked after arotinoid or RA. The thickness of the walls of the utricles also increased with increasing dose of retinoid, paralleling the changes in the epidermis. After doses of 0.1% RA and 0.001% arotinoid , the utricles resembled the hair follicles of hairless mice. Hyperplasia of the epidermis appears to be a primary effect of retinoids or rhino mouse skin. Hyperproliferation of the utricle wall is accompanied by a reduction in the size of the utricle lumen, preceding eventual differentiation of the utricles to normal-looking pilar units.

Animals↗
PubMed1984

Animal assays for anti-psoriatic, retinoid and sun protective agents.

It is possible to evaluate different dermatological therapeutic agents intended for human use in a variety of animal assays. This review will discuss some of these assays, and attempt to correlate animal and human skin responses. Psoriasis is a disease where changes in epidermal proliferation may be an important factor. It is possible to assay potential anti-psoriatic agents by measuring their ability to suppress DNA synthesis in the epidermis of hairless mice. This assay is predictive of the anti-psoriatic effectiveness of numerous agents including a variety of anti-proliferative drugs and anthralin, and has been used to evaluate the potential efficacy of purified coal tar shampoos and body preparations. The activity of the polyamine biosynthesis enzyme ornithine decarboxylase (ODC) is elevated in psoriatic skin, and it is induced in mouse epidermis by tape stripping. Retinoids can inhibit the induction of ODC activity, and this inhibition may be used to evaluate novel synthetic retinoids. Retinoids have beneficial effects on the abnormal keratinization found in various diseases. Rhino mice have multiple keratin-filled epidermal utricles, and the size of these is reduced by retinoid treatment. Observing the changes in the size of the utricles can be utilized to evaluate the effects of retinoids on keratinization. Sunscreen agents are tested on human volunteers by observing their ability to inhibit the erythema induced by exposure to solar-simulated light, to obtain a sun protection factor (SPF). It is possible to utilize the ability of sunscreens to inhibit other actinic-induced changes in the skin using animals. Parameters that may be measured include changes in DNA synthesis and ODC activity in the epidermis following ultraviolet irradiation. Some of these assays correlate well with human SPF determinations.

Adolescent↗
PubMed1984

Psoralen and ultraviolet A effects on epidermal ornithine decarboxylase induction and DNA synthesis in the hairless mouse.

8-Methoxypsoralen (8-MOP), 3-carbethoxypsoralen (3-CP), and 5-methoxypsoralen (5-MOP), with and without ultraviolet A (UVA), were compared as inducers of epidermal ornithine decarboxylase (ODC) and modulators of epidermal DNA synthesis in vivo in female Skh:hairless-1 albino mice. Both 8- and 5-MOP plus UVA induced epidermal ODC. Peak ODC activity was induced 24 hours after treatment, and ODC activity was still elevated at 48 hours. These same treatments also suppressed epidermal DNA synthesis 4 hours after treatment, as measured by tritiated thymidine incorporation. The psoralen 3-CP, which lacks the DNA monoadducts, failed to induce epidermal ODC either alone or with UVA and stimulated rather than suppressed incorporation of the tritiated thymidine.

Animals↗
PubMed1983

Etretinate therapy for psoriasis: clinical responses, remission times, epidermal DNA and polyamine responses.

A prospective study was carried out over 12 months involving twenty patients with psoriasis vulgaris who were treated with all-trans-aromatic derivative of vitamin A, etretinate. Etretinate was found to be an effective therapy for this skin disorder. Arthritis accompanying psoriasis vulgaris in four of seven of our patients was greatly improved by retinoid therapy. Side effects were found to be dose-related and included mucocutaneous abnormalities as well as abnormalities of blood lipids and liver function tests. Maintenance therapy appears to be required in nearly all patients, with relapse occurring within approximately 8 weeks. Polyamine biosynthesis has been determined previously to be accelerated in patients with psoriasis vulgaris. Polyamines (putrescine [Pu], spermidine [Sp], and spermine [Sm] were measured in skin samples of six patients with stable plaque-stage psoriasis before treatment and at 4 weeks during treatment. Pu, Sp, Sm levels, as well as the Sp/Sm ratio, fell. Epidermal DNA synthesis is increased in involved and noninvolved psoriatic skin; it was measured before and during treatment (at 4 weeks) in this study and found not to fall significantly during this period of time. Polyamine levels therefore decreased prior to any significant expected decrease in epidermal DNA synthesis measured in both involved and uninvolved skin.

Adult↗
PubMed1983

Anthralin: historical and current perspectives.

Anthralin was first synthesized in 1916. Earlier, a natural product, chrysarobin, originally derived from the South American araroba tree, had been used to treat psoriasis. Anthralin was first used in Germany, and later in the Ingram regimen in Britain, but it has never been popular with American dermatologists. This is probably due to the side effects of staining and irritation of the skin. Attempts to reduce these using low concentration, short contact therapy, and concomitant steroid therapy, have been only partially successful. It may be that better instruction of patients and physicians will lead to wider use of this effective topical agent for the treatment of psoriasis. The mode of action of anthralin is thought to be either through its effect on deoxyribonucleic acid (DNA), probably mitochondrial DNA, which reduces cell turnover, or through its effects on various enzyme systems, including those of polyamine synthesis and respiration. The aims of this review are to discuss historical aspects of anthralin and to update its chemistry, pharmacology, and clinical usage.

Anthracenes↗
PubMed1983

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↗