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Advances in Basic Research and Therapy
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Proceedings of the International Dermatology Symposium (IDS), Berlin, October 13-15, 1980
Pharmacology and Toxicology of Retinoids.- From Vitamin A to Retinoids: Chemical and Pharmacological Aspects.- Pharmacokinetics and Metabolism of Oral Aromatic Retinoids.- In vivo Immunostimulating Properties of Two Retinoids: Ro 10-9359 and Ro 13-6298.- Vitamin A Transport and Delivery and the Mechanism of Vitamin A Toxicity.- Experimental Toxicology of the Aromatic Retinoid Ro 10-9359 (Etretinate).- Studies in Reproductive Toxicology and Mutagenicity with Ro 10-9359.- Cytogenetic Studies in Patients Treated with Oral Retinoid Ro 10-9359.- Chromosomal Analysis in Patients Treated with the Oral Aromatic Retinoid Ro 10-9359.- Biological Effects of Retinoids.- Retinoids: New Developments in Their Mechanism of Action as Related to Control of Proliferative Diseases.- The Effects of Retinoids on Stratum Corneum. Structure and Function.- Light- and Electron Microscopic Changes of Human Epidermis Under Oral Retinoid Treatment.- Retinoid-Stimulated Material in Psoriatic Epidermis During Ro 10-9359 Therapy.- Effects of Oral Retinoid on Dermal Components in Human and Animal Skin.- Retinoid-binding Proteins and the Plasma Transport of Etretinate (Ro 10-9359) in Man.- Biochemical Mechanism of Modulation of Skin Carcinogenesis by Retinoids.- Mitogenic Properties of Aromatic Retinoids: in vivo and in vitro Effects on Epidermal Cells.- On the Effects Induced by Aromatic Retinoid Ro 10-9359 on Explants of Skin from Psoriatic Patients.- Effects of Retinoids on Keratinocytes in vitro.- Influence of Retinoid on Human Blood Cells in vitro. TMMP-retinoid Inhibits the Mitogenic Properties of Lectins and Modulates the Lymphocytic Response.- Ro 10-9359 Retinoid Inhibits Both in vitro Epidermal Cell Proliferation and Differentiation.- Application of Oral Retinoids in Psoriasis.- Aromatic Retinoids in Psoriasis: Clinical, Histological, Histochemical, Electron Microscopical and Immunological Investigations.- Intermittent Dose Schedule of Retinoids (Ro 10-9359) for Long-term Follow-up on Psoriasis (Preliminary Report).- Treatment of Severe Forms of Psoriasis with a Retinoic Acid Derivative: Ro 10-9359.- Treatment of Psoriasis Vulgaris with a Low-dosage Ro 10-9359 (Tigason) Orally Combined with Corticosteroids Topically.- Aromatic Retinoid (Ro 10-9359), RePUVA and PUVA in the Treatment of Psoriasis.- Clinical Observations on Oral Retinoid Therapy of Psoriatic Arthropathy (Ro 10-9359).- Application of Oral Retinoids in Acne.- Effects of Retinoids on the Sebaceous Glands of the Hamster Flank Organ.- Effects of Two Retinoids in Animal Experiments and After Clinical Application in Acne Patients: 13-cis Retinoic Acid Ro 4-3780 and Aromatic Retinoid Ro 10-9359.- Oral Retinoids: Effects on Human Sebaceous Glands and Nodulocystic Acne.- Oral Vitamin A (Retinol) in Acne Vulgaris.- 13-cis Retinoic Acid in Acne (A Double-blind Study of Dose Response).- Effects of 13-cis Retinoic Acid on Sebaceous Glands in Humans.- A Clinical Trial of the Use of Tigason (Ro 10-9359) in Male Patients with Severe Acne Vulgaris.- Oral Retinoid Therapy of Miscellaneous Disorders of Skin and Oral Mucosa.- Treatment of Lichen Planus and Leukoplakia with the Oral Retinoid Ro 10-9359.- Comparative Analysis of Two Retinoids in the Treatment of Disorders of Keratinization.- Long-Term Follow-up of 30 Children Under Oral Retinoid Ro 10-9359..- Treatment of Erythrokeratodermia Variabilis with Oral Retinoid (Ro 10-9359).- Ultrastructural Study of the Four Main Types of Ichthyosis After one Month's Treatment with Ro 10-9359.- Effect of Retinoids on Precancerous Lesions of Oral Mucosa.- Treatment of Parapsoriasis en Plaques and Mycosis Fungoides with an Oral Aromatic Retinoid (Ro 10-9359).- Effects of Retinoid Ro 10-9359 Alone or in Combined Therapy in Several Skin Diseases - Clinical Observations and Biochemical Data.- Effect of Systemic Ro 10-9359 Treatment of Immunological Parameters in Darier's Disease.- Freeze-Fracture Study of Psoriatic Lesions After Oral Administration of Retinoid.- Psoriasiform Dermatitis in Patients with Skin Diseases Other than Psoriasis as Side Effect of Ro 10-9359.- Immunological Features of Psoriasis: Effects of Ro 10-9359, Concanavalin A, Pokeweed Mitogen and Methotrexate on Cultivated Lymphocytes.- Prevention of Psoriasiform Reactions After Beta-Receptor Blockers by Retinoid.- Treatment of Psoriasis by Oral PUVA-Therapy Combined with Aromatic Retinoid (Re-PUVA).- Clinical and Laboratory Monitoring of Oral Retinoid Therapy.- The Posology of Oral Retinoids: How Much, How Often, How Long?.- Long-Term Biological Tolerance of Ro 10-9359.- Some Hepatotoxic Side Effects Observed in Patients Treated with an Aromatic Retinoid (Ro 10-9359).- Elevation of Serum Triglyceride Levels from Ora113-cis-Retinoic Acid.- A Proposal for Computing the Dosage of the Aromatic Retinoid Ro 10-9359 in Relation to Skin Surface.- Ro 10-9359 in Psoriasis: Prospective Liver Biopsy Study of Potential Hepatotoxicity.- Polarized Light Examination and Scanning Electron Microscopic Study of Hair in Patients Treated with Aromatic Retinoids for a Long Time.- Retinoid and Skin Cancer Prevention.- Aromatic Retinöid and 13-cis-Retinoic Acid: Spermatological Investigations.- Aromatic Retinoid in the Treatment of Multiple Superficial Basal Cell Carcinoma, Arsenic Keratosis and Keratoacanthoma.- Ro 10-9359 in Epidermodysplasia Verruciformis. Preliminary Report.- Oral Aromatic Retinoid (Ro 10-9359) Treatment of Two Patients Suffering with the Severe Form of Epidermodysplasia Verruciformis.- Lack of Enhancement of Experimental Photocarcinogenesis by Retinoic Acid.- Oral Treatment of Psoriasis with the Aromatic Retinoid Ro 10-9359.- Treatment of Darier's Disease with Systemic Ro 10-9359 (Tigason) - a Retinoic Acid Derivative.- Thermography of Psoriasis. Effects of Retinoids.- Short Clinical and Experimental Reports.- Results of Oral Retinoid Therapy in Different Forms of Psoriasis.- Topical Aromatic Retinoid in the Treatment of Ichthyosis Vulgaris.- Combined UVB Phototherapy and Low-dosage Oral Retinoid (Ro 10-9359) for Psoriasis Responding Inadequately to UVB Alone.- Oral Retinoid Promotion of UV Light Action in Psoriasis. A Measure of UV Radiation Protection.- Treatment of Epidermodysplasia Verruciformis or Multiple Verrucae Planae by Oral Aromatic Retinoid (Ro 10-9359-Tigason).- The Influence of Topical and Oral Retinoid Treatment on Photocarcinogenicity in Hairless Albino Mice.- Richner-Hanhart Syndrome - Tyrosinemia Type II and Oral Aromatic Retinoid (Ro 10-9359). Report of two Cases.- Light and Electron Microscopy Studies in Psoriasis Before and After Treatment with Retinoids (Ro 10-9359).- Electron Microscopic Characterization of the Mucus-like Material of the Epidermis Before and After Retinoid and Retinoid-PUVA (RePUVA) Treatment of Psoriasis.- Long-term Effects of All-trans-retinoic Acid on Epidermal Glycosaminoglycan, Glycoprotein and Protein Synthesis in vitro.- Clinical Aspects and Side Effects of Therapy with Oral Administration of Retinoids in Various Skin Diseases.- Treatment of Severe Psoriasis by Ro 10-9359.- Treatment of Psoriasis and Other Dermatoses with a New Aromatic Retinoid (Ro 10-9359).- Isoaccepting Serine t-RNAs Pattern as Marker of Epidermal Differentiation: its Alterations Under Retinoids.- Influence of Retinoic Acid on Epidermal Wound Healing in Man.- Ro 10-9359 and Pregnancy.- Elevated Levels of Triglycerides in Patients with Skin Disease Treated with Oral Aromatic Retinoid. The Significance of Risk Factors.- Present Status and Perspectives.- Biological Effects of Retinoids.- The Use of Oral Aromatic Retinoid in Psoriasis Therapy: an Overview of Past, Present and Future Developments.- Closing Remarks on Acne.
With the aromatic retinoic acid analog Tigason oral and intravenous pharmacokinetic studies have been performed in 5 normal volunteers. Simultaneous fitting of single i. v. and oral data to a three-compartment model assuming first-order absorption was possible. Using Nonlin parameter estimates of the single-dose data, one is able to predict the decline in plasma levels of parent drug following cessation of a 10 days multiple dosing regimen up to 24 hours. The model is however unable to predict a phase of prolonged elimination observed beyond 24 hours. Moreover in 5 patients, who underwent chronic therapy (8-15 months), substantial plasma levels of both unchanged drug and main metabolite (corre­ sponding carboxylic acid) were observed up to 140 days after cessation of the therapy. An apparent half-life of elimination of 80-100 days can be calculated. The drug appears to be stored at some yet unknown storage site. Investigation of metabolism of Tigason in rats and humans revealed 19 different bio­ transformation products thus far, most of them appearing in the urine in low amounts (20010 of dose). A few of them (mainly the acid Ro 10-1670) after conjugation to glucuronic acid are excreted in the bile in high amounts (60-80% of dose). No drug appeared unchanged in the excreta after i. v. administration to rats. References 1. Bollag W (1971) Effects of vitamin A acid (NSC-122758) on transplantable and chemically-induced tumors. Cancer Chemother Rep 55:53-58 2.

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