Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

9-cis-Retinoic acid (9-cis-RA) and all-trans-RA (ATRA) are naturally occurring hormones. The nuclear receptors that mediate the effects of retinoids are the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs). ATRA binds RAR with high affinity but does not bind to RXR, whereas 9-cis-RA, an isomer of ATRA, is a ligand that binds and transactivates both RARs and RXRs. The goals of this study were to determine the safety, tolerability, pharmacokinetics, and metabolic profile of 9-cis-RA in advanced cancer patients. Forty-one patients received oral 9-cis-RA (ALRT1057; Panretin capsules) at doses ranging from 5-140 mg/m2/day. Twenty-six patients were treated once daily with up to 140 mg/m2; a subsequent cohort of 15 patients were treated twice daily (b.i.d.) at 100-140 mg/m2/day (50, 60, and 70 mg/m2 b.i.d.) to evaluate a b.i.d. dosing regimen. Headache was the most frequent adverse event and was dose limiting in 3 of 41 patients. Skin toxicity was the next most common toxicity and was seen in 11 of 41 patients; it was typically mild and limited to skin dryness and erythema. Other toxicities included conjunctivitis, flushing, diarrhea, transaminitis, hypercalcemia, and asymptomatic hypertryglyceridemia. Toxicities were typically dose related, occurred primarily above 83 mg/m2/day, and were not ameliorated by b.i.d. dosing. No tumor responses were observed. The mean day 1 area under the plasma concentration-time curve and peak plasma concentration values were dose-proportional over all dose levels, whereas day 15 area under the plasma concentration-time curve and peak plasma concentration values were nonlinear above 83 mg/m2/day, suggesting that 9-cis-RA induced its own metabolism at doses equal to and above 140 mg/m2/day. 9-cis-RA is a retinoid receptor pan agonist with a more favorable pharmacokinetic and toxicity profile than that observed with previously studied retinoids and merits further investigation.
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PMID:Phase I study of 9-cis-retinoic acid (ALRT1057 capsules) in adults with advanced cancer. 962 60

The effects of spray-drying of the unicellular microalga Dunaliella salina on its beta-carotene content and geometric isomer composition have been studied. The efficacy of a range of synthetic and natural antioxidants in preventing degradation of beta-carotene has been determined. Losses of beta-carotene and isomerization were minimal during processing for both the control (no exogenous antioxidants) and the samples containing butylated hydroxytoluene (BHT) and tert-butylhydroquinone (TBHQ). However, the use of tocopherol-based antioxidants resulted in degradation of 52-72% of beta-carotene during the drying process. All dried powders of Dunaliella proved to be unstable during storage in the presence of light and air, with beta-carotene degraded according to a first-order kinetic model. Of the antioxidants studied, only TBHQ was successful in significantly minimizing degradation (degradation constants of 0.03 and 0.04 days(-)(1), compared to 0.53 days(-)(1) for the respective control). For control powders and those with BHT added to the feed, the degradation constants were reduced to values between 0.27 and 0.37 days(-)(1) by restricting light and flushing with nitrogen; however, storage in the dark alone had no effect. For more slowly degrading powders having TBHQ added to the feed, it was clear that degradation of beta-carotene was influenced by both light and oxygen. During storage the 9-cis isomer of beta-carotene was significantly more unstable than the all-trans form. TBHQ was, however, successful in reducing relative losses of this isomer for samples stored in the dark. The results suggest a dominant photodegradative mechanism for the loss of the 9-cis isomer of beta-carotene.
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PMID:Spray-drying of the microalga Dunaliella salina: effects on beta-carotene content and isomer composition. 1055 90

The aged appearance of skin following repeated exposure to solar ultraviolet (UV) irradiation stems largely from damage to cutaneous connective tissue, which is composed primarily of type I and type III collagens. We report here that a single exposure to UV irradiation causes significant loss of procollagen synthesis in human skin. Expression of type I and type III procollagens is substantially reduced within 24 hours after a single UV exposure, even at UV doses that cause only minimal skin reddening. Daily UV exposures over 4 days result in sustained reductions of both type I and type III procollagen protein levels for at least 24 hours after the final UV exposure. UV inhibition of type I procollagen synthesis is mediated in part by c-Jun, which is induced by UV irradiation and interferes with procollagen transcription. Pretreatment of human skin in vivo with all-trans retinoic acid inhibits UV induction of c-Jun and protects skin against loss of procollagen synthesis. We have reported previously that UV irradiation induces matrix-degrading metalloproteinases in human skin and that pretreatment of skin with all-trans retinoic acid inhibits this induction. UV irradiation, therefore, damages human skin connective tissue by simultaneously inhibiting procollagen synthesis and stimulating collagen breakdown. All-trans retinoic acid protects against both of these deleterious effects and may thereby retard premature skin aging.
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PMID:c-Jun-dependent inhibition of cutaneous procollagen transcription following ultraviolet irradiation is reversed by all-trans retinoic acid. 1097 19