Reference

Potentiation of the teratogenic effects induced by coadministration of retinoic acid or phytanic acid/phytol with synthetic retinoid receptor ligands

Potentiation of the teratogenic effects induced by coadministration of retinoic acid or phytanic acid/phytol with synthetic retinoid receptor ligands. Elmazar, M. M. A.; Nau, H. (Department of Food Toxicology, School of Veterinary Medicine, Hannover 30173, Germany). Archives of Toxicology, 78(11), 660-668 (English) 2004 Springer GmbH. CODEN: ARTODN. ISSN: 0340-5761. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Section cross-reference(s): 4, 18 Previous studies in our lab. identified retinoid-induced defects that are mediated by RAR-RXR heterodimerization using interaction of synthetic ligands selective for the retinoid receptors RAR and RXR in mice (Elmazar et al. 1997). The present study was designed to investigate whether these RAR-RXR heterodimer-mediated defects can be also induced by interactions of natural and synthetic ligands for retinoid receptors.In this article, certain chemicals are used. Some of their cas registry numbers are 153559-49-0 and 14721-66-5 A non-teratogenic dose of the natural RXR agonist phytanic acid (100 mg/kg orally) or its precursor phytol (500 mg/kg orally) was coadministered with a synthetic RARa-agonist (Am580; 5 mg/kg orally) to NMRI mice on day 8.25 of gestation (GD8.25). Furthermore, a non-teratogenic dose of the synthetic RXR agonist LGD1069 (20 mg/kg orally) was also coadministered with the natural RAR agonist, all-trans-retinoic acid (atRA, 20 mg/kg orally) or its precursor retinol (ROH, 50 mg/kg orally) to NMRI mice on GD8.25. The teratogenic outcome was scored in day-18 fetuses. The incidence of Am580-induced resorptions, spina bifida aperta, micrognathia, anotia, kidney hypoplasia, dilated bladder, undescended testis, atresia ani, short and absent tail, fused ribs and fetal wt. retardation were potentiated by coadministration of phytanic acid or its precursor phytol. Am580-induced exencephaly and cleft palate, which were not potentiated by coadministration with the synthetic RXR agonists, were also not potentiated by coadministration with either phytanic acid or its precursor phytol. LGD1069 potentiated atRA- and ROH-induced resorption, exencephaly, spina bifida, aperta, ear anotia and microtia, macroglossia, kidney hypoplasia, undescended testis, atresia ani, tail defects and fetal wt. retardation, but not cleft palate. These results suggest that synergistic teratogenesis can be induced by coadministration of a natural RXR ligand (phytanic acid) with a synthetic RAR agonist (Am580). Thus, certain potentially useful therapeutic agents or nutritional factors such as phytanic acid should be tested for teratogenic risk by coadministration with other retinoid receptor agonists. .

Treatment of mycosis fungoides and Sezary syndrome: recent advances and novel therapies

All Rights Reserved. Treatment of mycosis fungoides and Sezary syndrome: recent advances and novel therapies. Scarisbrick, Julia (Skin Tumor Unit, St Thomas Hospital, St John's Institute of Dermatology, London SE1 7EH, UK). Expert Review of Dermatology, 1(4), 569-577 (English) 2006 Future Drugs Ltd. CODEN: ERDXAB. ISSN: 1746-9872. DOCUMENT TYPE: Journal; General Review CA Section: 1 (Pharmacology) Section cross-reference(s): 8 A review.There are some reagents with their cas registry numbers 66-97-7 and 153559-49-0 are used in this study. Early-stage mycosis fungoides (stage IA-IIA) may be treated with skin-directed therapy (topical corticosteroids, topical mechlorethamine, superficial radiotherapy and phototherapy). Advanced or refractory disease may require systemic therapy, such as chemotherapy, extracorporeal photopheresis (ECP) or immunotherapy. Although chemotherapy produces a good response in cutaneous T-cell lymphoma (CTCL), it is frequently short lived. Morbidity is common with chemotherapy and infection or septicemia may be preterminal. There has been a burst of novel therapies for the treatment of advanced and refractory CTCL over the past decade, including retinoid X receptor-selective retinoids, monoclonal antibodies, immunotherapy and histone deacetylase inhibitors. Most of these therapeutic agents are still being developed and are being used in Phase I-III clin. trials. However, bexarotene, a retinoid X receptor-selective retinoid, was approved for the treatment of CTCL in 1999 and has efficacy in both early and advanced disease. It may be used alone or in combination with psoralen plus UVA (PUVA), ECP or interferon. As with other forms of low-grade lymphoma, CTCLs are responsive to treatments but readily relapse and cure is rarely achieved. Stem cell transplants are being investigated currently as a potential curative therapy in advanced/refractory CTCL in patients with a good performance status. .