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Biomedical subjects

O Rollman

Publications and source records attributed to O Rollman.

At least 37 records · Page 2Linked to original sources
PubMed1990

Isotretinoin treatment of severe acne affects the endogenous concentration of vitamin A in sebaceous glands.

An investigation of pooled skin samples from 22 acne patients has shown that isotretinoin and its major metabolite, 4-oxo-isotretinoin, can be detected in sebaceous glands during treatment with isotretinoin (1 mg/kg/d for 4 months). The levels are less than those in the epidermis, thus excluding selective drug distribution as a prime explanation for drug function. Oral isotretinoin markedly increases retinol levels and decreases dehydroretinol levels in the skin while on therapy. The effect is more pronounced in sebaceous glands than in epidermis and dermis. The increased retinol levels probably reflect a metabolic interference with endogenous vitamin A, since isotretinoin cannot be converted into retinol in vivo. Previous studies have shown that dehydroretinol accumulates in hyperproliferative, keratinizing skin lesions and so its reduction with isotretinoin therapy may relate to a reduction in cell proliferation or to dedifferentiation. However, the precise interrelationships of these observations need further elucidation.

Acne Vulgaris↗
PubMed1990

Acitretin excretion into human breast milk.

Retinoid transfer into breast milk was studied in a psoriatric woman receiving oral acitretin at a dosage of 40 mg once daily. Concentrations of the parent compound and its main metabolite, 13-cis acitretin, were measured in serum and mature milk during the initial nine days of therapy, using reverse-phase high performance liquid chromatography. At steady-state, trace amounts of the drug and metabolite (30-40 ng/ml) appeared in breast milk corresponding to a milk/serum concentration ratio of about 0.18. Acitretin was almost exclusively distributed in the fatty layers of the milk. Although the estimated amount of the drug consumed by a suckling infant would correspond to only 1.5% of the maternal dose, the toxic potential of acitretin justifies its avoidance in breast-feeding women.

Acitretin↗
PubMed1990

UV-induced isomerization of oral retinoids in vitro and in vivo in hairless mice.

Ultraviolet (UV) irradiation causes isomerization and destruction of many vitamin A analogues (retinoids). Using high-performance liquid chromatography (HPLC), we investigated in vitro and in vivo the effects of UV irradiation on 2 all-trans aromatic retinoids (etretinate and acitretin) and on 13-cis retinoic acid (isotretinoin). When etretinate and acitretin dissolved in ethanol were irradiated with UVB (280-320 nm; 10-336 mJ/cm2) or UVA (320-400 nm; 1-5 J/cm2), extensive and reproducible cis-isomerizations occurred at the 13-position (cis/trans ratio approximately 1.6 in all experiments) but there was no progressive photodegradation of the molecules. Irradiation of isotretinoin produced only moderate trans-isomerization but the sum of HPLC peak heights fell with increasing UV doses, being 72% of the original value after 336 mJ/cm2 of UVB. Hairless mice were given etretinate (50 mg/kg bw), acitretin (200 mg/kg) or isotretinoin (50 mg/kg) on days 1, 4 and 7 and were irradiated daily for 8 d with 13 mJ/cm2 UVB plus 1 J/cm2 UVA. Samples of serum, dorsal skin and liver were collected and retinoids analyzed by HPLC. In the etretinate and acitretin-treated, irradiated animals the serum concentrations of the 13-cis isomers were 2-6 times higher than in nonirradiated controls. Irradiated epidermis also contained significantly higher concentrations of 13-cis etretinate and 13-cis acitretin than did control epidermis. The serum and epidermal concentrations of all-trans etretinate and acitretin were unchanged or even increased after irradiation.(ABSTRACT TRUNCATED AT 250 WORDS)

Acitretin↗
PubMed1987

Clinical pharmacology of 3 generations of retinoids.

The bioavailability, plasma transport and tissue distribution of various retinoids are largely determined by their physicochemical properties; some are extremely lipidsoluble whereas others are relatively hydrophilic. Isotretinoin, a 1st generation retinoid, lacks the problematic affinity for fat. Etretinate, a 2nd generation aromatic retinoid, has been shown to accumulate in both fat tissues and in the adrenals. Etretin, the main free-acid metabolite of etretinate, is less lipophilic and is presently being tested as an alternative drug. Arotinoid ethyl ester, a 3rd generation aromatic retinoid which has as yet only undergone limited trials, is extremely potent making pharmacological evaluation difficult. The search for more potent retinoids has not so far resulted in a complete resolution of the efficacy and toxicity of the drugs.

Animals↗
PubMed1987

Hendersonula toruloidea infection: successful response of onychomycosis to nail avulsion and topical ciclopiroxolamine.

The exotic mould Hendersonula toruloidea may occasionally produce a ringwormlike, non-inflammatory, therapy-resistant mycosis of the skin and nails simulating chronic dermatophytosis. We report on a 30-year-old Nigerian male who, after two years' sojourn in Sweden, developed finger-nail dystrophy and mild scaling of the palm and sole skin due to H. toruloidea infection. Nail avulsion followed by long-term occlusive application of ciclopiroxolamine cleared the onychomycosis, whereas the sole and palm infection was resistant to ciclopiroxolamine and glutaraldehyde treatment.

Administration, Cutaneous↗
PubMed1986

Oral isotretinoin (13-cis-retinoic acid) therapy in severe acne: drug and vitamin A concentrations in serum and skin.

The disposition of oral isotretinoin to the skin and the effects of the drug on the vitamin A levels in serum and skin were studied in 17 patients with nodulocystic acne. All patients received 0.5 mg/kg/day for 3 months and 8 patients continued treatment with 0.75 mg/kg/day for another 3 months. The parent drug, the major metabolite (4-oxo-isotretinoin), and 2 natural retinoids (retinol and dehydroretinol) were monitored in serum and biopsies of uninvolved skin, using adsorption high-pressure liquid chromatography. During the initial 3 months of treatment the mean isotretinoin level in the serum was 145 ng/ml and in the epidermis 73 ng/g. The corresponding values for 4-oxo-isotretinoin were 615 and 113 ng/g, respectively. Even at the highest dosage there was no progressive accumulation of isotretinoin in serum, epidermis, or subcutis. After discontinuation of therapy the drug disappeared from both serum and skin within 2-4 weeks. The serum transport of vitamin A, monitored by the concentrations of retinol, retinol-binding protein, and prealbumin (transthyretin), was not affected by the treatment. By contrast, the retinol level in the epidermis increased by an average of 53% (p less than 0.01) and the dehydroretinol level decreased by 79% (p less than 0.001) as a result of 3 months of treatment. Both changes were reversible. The results suggest that isotretinoin therapy interferes with the endogenous vitamin A metabolism in the skin.

Acne Vulgaris↗
PubMed1986

Tissue distribution of aromatic retinoid (etretinate) in three autopsy cases: drug accumulation in adrenals and fat.

The problematic storage of etretinate in fat during chronic etretinate therapy prompted us to search for other "high-affinity" tissues in 3 patients studied at autopsy. Specimens from eleven organs were analysed for etretinate and its main metabolite, etretin, by high-performance liquid chromatography. The results confirmed an accumulation of etretinate in fat and to a lesser degree in liver. High levels of etretinate were also found in the adrenals and, in one case, this value exceeded that of the fat tissue. Low levels were observed in several other organs, notably the kidneys, brain and testis. With the possible exception of liver and gut, the metabolite did not accumulate in any particular organ. Although the available data is still limited, the risk that the accumulation of etretinate in the adrenals may adversely affect adrenal function must be examined.

Acitretin↗
PubMed1985

Psoriasis and vitamin A. Plasma transport and skin content of retinol, dehydroretinol and carotenoids in adult patients versus healthy controls.

The vitamin-A status of 107 patients with psoriasis and 37 healthy controls was investigated. The mean serum level of retinol-binding protein (RBP) was normal in the 79 patients with chronic plaque psoriasis covering 25% or less of the skin surface. In the 28 patients with more extensive plaque lesions or pustular/erythrodermic psoriasis, the mean serum RBP level was significantly lower than in the controls (P less than 0.05). The cutaneous concentrations of retinol (vitamin A1), dehydroretinol (vitamin A2) and carotenoids were measured in extracts of saponified shave-biopsy specimens of uninvolved and involved skin from 33 patients with plaque psoriasis. Their retinol values did not differ significantly from those found in control skin (mean, 252 ng/g), whereas the carotenoid levels in both uninvolved and involved skin were 25%-50% lower. In contrast, the dehydroretinol concentration was higher in the patients' involved skin (mean, 237 ng/g) than in their uninvolved skin (94 ng/g) and healthy control skin (70 ng/g; P less than 0.01). Although the origin of increased dehydroretinol levels in involved psoriatic skin is unknown, similar increments were observed in control epidermis in which proliferation had been induced by tape stripping. In 7 patients treated with oral etretinate (aromatic retinoid) for 2-3 weeks, the median retinol and dehydroretinol levels in involved skin increased by 107% and 212%, respectively; the vitamin-A concentrations in uninvolved skin did not change significantly. Oral treatment with beta-carotene/canthaxanthin raised the median carotenoid levels in uninvolved and involved skin by 170% and 610%, respectively, without significantly affecting the vitamin-A composition.

Adolescent↗
PubMed1985

Effects of long-term ketoconazole therapy on serum lipid levels.

Serum cholesterol and triglycerides were determined in 36 patients receiving an 8-month course of oral ketoconazole 200 mg/day in order to study its effect on lipid metabolism. The mean serum cholesterol concentration had decreased by 15% (p less than 0.001) after 1 month, but on continued medication it returned to the pretreatment state; after discontinuation of therapy it increased transiently by 13% (p less than 0.001). Triglycerides increased during ketoconazole administration and at the end of the trial the mean triglyceride concentration was 48% higher than the baseline value (p less than 0.02). Although most lipid values during therapy lay within the normal ranges, 6 patients developed transient hypertriglyceridaemia. There was no correlation between the changes in lipids and peak serum ketoconazole levels. In one subject studied in more detail the concentration of very low density lipoprotein triglycerides rose during therapy, whereas high density lipoprotein cholesterol decreased slightly. The lipoprotein lipase activity in muscle and, in particular, in adipose tissue was significantly suppressed during ketoconazole treatment. Serum lipids and, if possible, serum lipoproteins should be carefully monitored in patients receiving long-term oral ketoconazole therapy.

Adipose Tissue↗
PubMed1985

Vitamin A in skin and serum--studies of acne vulgaris, atopic dermatitis, ichthyosis vulgaris and lichen planus.

The concentrations of vitamin A and total carotenoids were measured in serum and skin of 61 patients with acne vulgaris, atopic dermatitis, ichthyosis vulgaris or lichen planus, and compared with those in 37 healthy subjects. The mean serum concentrations of retinol and retinol-binding protein were significantly decreased in patients with acne (P less than 0.01) and slightly increased in those with ichthyosis (P less than 0.05), but were otherwise normal. Serum carotenoid levels did not differ between patients and controls. Superficial shave biopsies from both involved and uninvolved skin were examined for the presence of retinol (vitamin A1), dehydroretinol (vitamin A2) and total carotenoids. The mean retinol concentration was increased in lichen planus lesions (P less than 0.05) and decreased in both acne skin (involved and uninvolved) and in lesions of atopic dermatitis (P less than 0.05). The mean dehydroretinol concentration was markedly increased in lesions of atopic dermatitis and lichen planus (P less than 0.01). No consistent abnormalities were found in skin of patients with ichthyosis vulgaris. The mean carotenoid concentration in the patients' skin did not differ significantly from that in the controls. The reduced retinol level in the skin of acne patients is probably explained by diminished supply of vitamin A from the blood. The abnormal ratio of retinol to dehydroretinol in lesions of lichen planus and atopic dermatitis is possibly due to changes in cutaneous vitamin A metabolism associated with epidermal hyperproliferation and inflammation.

Acne Vulgaris↗
PubMed1985

Differential hepatotoxicity of two oral retinoids (etretinate and isotretinoin) in a patient with palmoplantar psoriasis.

A 64-year-old woman developed biopsy-proven hepatitis during oral treatment of severe pustular psoriasis of palms and soles with an aromatic retinoid, etretinate. The elevations in hepatic enzyme levels reappeared when etretinate was reinstituted 18 months later. Analysis of serum and subcutis showed normal therapeutic concentrations of the drug. Isotretinoin therapy, although apparently devoid of hepatotoxicity, was clinically only marginally effective. Evidence compiled from the literature suggests that etretinate-hepatitis is a drug-specific reaction.

Chemical and Drug Induced Liver Injury↗
PubMed1984

Vascular effects of a local anesthetic mixture in atopic dermatitis.

An anesthetic cream with an eutectic mixture of 5% lidocaine and 5% prilocaine has been tested on the skin of healthy subjects and patients with atopic dermatitis and generalized eczema. In healthy subjects a blanching was seen when the analgesia was complete after 30-60 min. In the dry skin and eczematous lesions of atopic dermatitis an application time of 5-15 min caused a blanching and a good analgesia. When applied for 30-60 min the eczematous skin became increasingly red and in one patient purpura appeared. The white dermographism turned red in treated areas. The abnormal vascular reactions to the cream in diseased skin can be explained by a rapid and increased percutaneous absorption of the anesthetics. A shortened application time is here recommended.

Adolescent↗
PubMed1983

Retinoid concentrations in skin, serum and adipose tissue of patients treated with etretinate.

Synthetic and natural retinoids were analysed in epidermis, dermis, subcutis and serum of twenty-seven patients treated with etretinate (0.6-1.0 mg/kg/day) for 1-36 months. The concentrations of etretinate (including its major metabolite) in serum and normal-appearing epidermis were 150-600 ng/ml and 50-350 ng/g, respectively. The serum and epidermal values were significantly correlated (P less than 0.05). The drug progressively accumulated in the subcutis attaining a maximum value of 15,500 ng/g. After the treatment, etretinate disappeared from the epidermis within 1 week. By contrast, the drug remained in the subcutis for several months after cessation of treatment. The epidermal composition of endogenous retinoids changed during etretinate therapy as reflected in an increased ratio of 3-dehydroretinol to all-trans retinol.

Acitretin↗
PubMed1982

Vitamin A in human skin: II Concentrations of carotene, retinol and dehydroretinol in various components of normal skin.

Pro-vitamin A(beta-carotene) and the predominant forms of vitamin A in human skin (retinol and dehydroretinol) were analyzed in hydrolyzed specimens from 4 cadavers and 22 healthy subjects. Beta-carotene was identified in extracts of epidermis by its specific absorption spectrum. Vitamin A was determined by high-pressure liquid chromatography. The concentrations were related to the wet weight or protein content of the sample. The analysis of different skin compartments showed that the concentrations of the 3 constituents were usually related as follows: carotene greater than retinol greater than dehydroretinol. The concentrations were always higher in the epidermis than in the upper dermis. Skin surface lipids contained carotene and retinol but not in amounts sufficient to contribute to the higher epidermal values. Analysis of epidermal autopsies from 5 different skin areas (back, breast, arm, leg and foot) and of epidermal biopsies from the back of the healthy subjects showed that the interindividual differences were larger for carotene and dehydroretinol than for retinol, whereas the intraindividual variations were larger for retinol. The mean (+/- SD) concentrations of carotene, retinol and dehydroretinol in back skin epidermis of healthy subjects were 13 +/- 5, 1.7 +/- 0.4 and 0.4 +/- 0.2 microgram/g protein, respectively. No significant variations with age and sex were found.

Carotenoids↗