Aromatic Retinoid Research Articles

Determination of an aromatic retinoid and its main metabolite by high-performance liquid chromatography.

Determination of an aromatic retinoid and its main metabolite by high-performance liquid chromatography.

Epidermolytic hereditary palmoplantar keratoderma. Report of a family and treatment with an oral aromatic retinoid.

This study describes a family of 30 people in which 14 members have hereditary epidermolytic palmoplantar keratoderma. Four patients were treated with an oral aromatic retinoid for up to 5 months. They responded in a uniform and dramatic way: 10-14 days after the onset of therapy, the hyperkeratotic horny layer was sequestered in large sheets resulting in normal appearing skin and restoration of normal surface sensitivity. Biopsies revealed that the underlying disorder of keratinization had remained unchanged. Treatment with the retinoid had to be discontinued as the sensitivity and vulnerability restricted normal function of hands and feet.

Oral treatment of ichthyosis with an aromatic retinoid.

An aromatic retinoid (Ro-10/9359) was used for oral treatment of five cases of ichthyosis (three lamellar, two X-linked. Complete clearing of the skin lesions was achieved in all five patients within 24.2 +/- 3.2 days (X-linked 21.75 +/- 6.5, lamellar 23 days). Histopathology showed reduction of the hyperkeratosis, and thickening of the granular layer. Clinical side effects were of mild intensity and included cheilitis, conjunctivitis and pruritus. All side effects were reversible upon reduction of the daily dosage. In three patients treatment was discontinued after clearing of lesions. Fresh lesions re-appeared 6 weeks later. One patient with X-linked ichthyosis developed two recurrences during maintenance treatment; one patient with lamellar ichthyosis was kept in complete remission for 9 weeks on a reduced daily dosage.

Oral Treatment of Keratosis Follicularis With a New Aromatic Retinoid

Four patients with extensive keratosis follicularis (Darler's disease) showed excellent clinical response to the oral administration of a new aromatic derivative of retinoic acid (RO 10-9359). Initial oral treatment with 50 to 75 mg of the drug was followed by substantial improvement in four to seven days and the lesions cleared completely after three to four weeks. Long-term treatment with 25 to 30 mg/day was sufficient to prevent recurrence. No serious side effects were seen with this dosage after several months. Some dryness of the lips and the nasal mucosa occurred and one patient experienced slight nausea. Histological investigations showed the gradual disappearance of acantholysis, dyskeratosis, and hyperkeratosis, in this order. The given therapeutic schedule is a reliable routine management for keratosis follicularis in adults.

Oral treatment of keratosis follicularis with a new aromatic retinoid

Oral treatment of keratosis follicularis with a new aromatic retinoid

Biochemical treatment of precancerous oral lesions: The effectiveness of various analogues of retinoic acid

Leukoplakia is neither a clinical, aetiological nor histopathological entity. Therefore treatment is difficult particularly in multifocal and advanced lesions. Since 1970, we have tested the therapeutic effect of different derivatives of all-trans-retinoic acid. The study includes 75 cases with homogeneous leukoplakia without or with minimal epithelial dysplasia. Over 60% of the cases treated showed positive early results. In follow-ups from 1 to 6 years about 45% of cases showed complete or partial remission. The rest showed relapses or even progression. In cases with recurrence without changes in the morphological characteristics, positive effects were achieved with 1 to 4 repeated courses of therapy. All derivatives of retinoic acid tested so far have shown undesirable side effects with systematic manifestations or local symptoms: interruption of treatment (4) or reduction of dosage (9) were unavoidable for that reason. Regarding the side effects, retinoic acid should only be given under clinical supervision. Of the derivates tested to date, aromatic retinoid seems to have the best curative potential in homogenic leukoplakia.

Systemic Treatment of Psoriasis with a New Aromatic Retinoid

Systemic Treatment of Psoriasis with a New Aromatic Retinoid

A fine structural study on the therapeutic effect on an aromatic retinoid on chemically-induced skin papillomas of the mouse

Skin papillomas induced by dimethylbenzanthracene and croton oil were treated systemically with a single injection of an aromatic new retinoid (Ro 10-9359). A marked regression of the tumors occurred within 7 days. The effects of this drug as seen with the electron microscope were (a) a marked enhancement of production of mucopolysaccharides and their secretion into the extracellular space, (b) a labilization of the plasma membrane resulting in vacuolization and loss of cytoplasmic constituents into the extracellular space, (c) an increase in lysosomal organelles, (d) formation of many necrotic cells. There were no clear-cut effects on either the nuclei, nucleoli or cytoplasmic constituents such as ribosomes and tonofibrils, nor was there any increase in the number of gap junctions as seen in keratoacanthomas after local retinoic acid treatment. Our interpretation favours the hypothesis that cell necrosis is mainly due to the labilization of the plasma membrane, but that other effects like the enhanced mucopolysaccharide production secreted into the extracellular space, might also play a role in the regression of the papillomas.

Autoradiographic and Histopathologic Studies on the Mode of Action of an Aromatic Retinoid (Ro 10-9359) on Chemically Induced Epithelial Tumors in Swiss Mice

The mode of action of an aromatic analogue of retinoic acid, ethyl all-trans-9-(4-methoxy-2,3,6-trimethyl-phenyl)-3,7-dimethyl-2,4,6,8-nonatetraenoate (Ro 10-9359), a compound known to possess a considerable prophylactic and therapeutic effect on skin papillomas and carcinomas, was investigated with autoradiographic and histopathologic methods. The ip application of a single dose of 1,000 mg Ro 10-9359/kg to female Swiss mice with chemically induced skin papillomas caused a 29% regression of the mean tumor diameter after 3 days and a 51% regression after 7 days. In the tumors, the number of DNA-synthesizing cells [measured by the labeling index (LI)] and the length of the cell cycle were not affected by the retinoid; thus a mode of action at the level of cell proliferation can be excluded. In the normal skin, an increase in the LI of about 30% was observed. A small effect on the cell loss was observed; however, it was not sufficient to explain quantitatively the regression of the tumors. When measured histometrically, it appeared that the loss of the horn and the formation of necroses, 3-10 times larger than in the placebo groups, were mainly responsible for the tumor regressions caused by the retinoid. After 7 days, the proportion of stroma in the tumors was increased, and dilation of the vessels and edema in the stroma proximal to the necroses were frequent.