Disease relevance of Vitamin A acid

• Toxicity was generally mild, though greater in the group given low-dose isotretinoin therapy [1].
• Prevention of second primary tumors with isotretinoin in squamous-cell carcinoma of the head and neck [2].
• During two years of treatment with isotretinoin, there were 25 tumors (mean, 5; range, 3 to 9), with an average reduction in skin cancers of 63 percent (P = 0.019) [3].
• Patients were treated with isotretinoin at a dosage of 2 mg per kilogram of body weight per day for two years and then followed for an additional year, without the drug [3].
• Prevention of skin cancer in xeroderma pigmentosum with the use of oral isotretinoin [3].

Psychiatry related information on Vitamin A acid

• There were no differences in the severity of depressive symptoms between the isotretinoin and antibiotic treatment groups before or after treatment [4].
• Isotretinoin treatment of a woman with bipolar disorder [5].
• Many systemic drugs may produce ocular toxicity, including bisphosphonates, topiramate, vigabatrin, isotretinoin and other retinoids, amiodarone, ethambutol, chloroquine and hydroxychloroquine, tamoxifen, quetiapine, cyclo-oxygenase (COX)-2 inhibitors, erectile dysfunction agents and some herbal medications [6].
• Hypersomnia associated with isotretinoin in a patient with recurrent major depressive disorder and acne vulgaris [7].
• Increased use of mental health services related to Isotretinoin treatment: a 5-year analysis [8].

High impact information on Vitamin A acid

• Suppression of retinoic acid receptor-beta in premalignant oral lesions and its up-regulation by isotretinoin [9].
• Isotretinoin for juvenile chronic myelogenous leukemia [10].
• Among 124,216 women with completed telephone or mail follow-up results, there were 402 pregnancies during therapy (3.4 per 1000 courses of isotretinoin); 72 percent of the pregnant women had elective abortions, 16 percent spontaneous abortions, 3 percent ectopic pregnancies, and 8 percent live births [11].
• The only toxic effect of isotretinoin therapy was cheilitis in two patients [12].
• However, a high rate of relapses and toxic reactions led us to conduct a trial of a much lower dose of isotretinoin in the hope of maintaining a response and limiting toxicity [1].

Chemical compound and disease context of Vitamin A acid

• Oral administration of isotretinoin (13-cis retinoic acid) was shown previously (Kraemer, K. H., J. J. DiGiovanna, A. N. Moshell, R. E. Tarone, and G. L. Peck. 1988. N. Engl. J. Med. 318:1633-1637) to reduce the frequency of skin cancers in xeroderma pigmentosum (XP) patients [13].
• Cutaneous T-cell lymphoma and calcitriol and isotretinoin treatment [14].
• It is shown here by using a quantitative fluorescence technique, that Accutane (13-cis-retinoic acid), a drug used in the treatment of acne but that causes night blindness, binds to RPE65 with a K(D) of 195 nM [15].
• These trials include studies to develop clinically applicable intermediate markers of carcinogenesis and large Phase III trials to evaluate the efficacy of the retinoid isotretinoin in preventing second primary tumors following head and neck or lung cancers [16].
• This phase II, cross-over, randomized study of advanced, predominantly androgen-dependent prostate cancer patients was designed to assess primarily the effect on prostate-specific antigen (PSA) decline and toxicity of adding isotretinoin to hormonal therapy and, secondarily, the potential antitumor activity of the combination [17].

Biological context of Vitamin A acid

• Two infants with prominent frontal bossing, hydrocephalus, microphthalmia, and small, malformed, low-set, undifferentiated ears were born to mothers who had taken isotretinoin in the first trimester of pregnancy [18].
• The present observations suggest that isotretinoin acts as a scavenger of such radiation products, thereby providing protection against x-ray-induced chromatid damage [13].
• The sc route was used to study the adjuvant effect of vitamin A palmitate (VA) and the retinoids isotretinoin (Ro 4-3780), etretinate (Ro 10-9359), and motretinide (Ro 11-1430) on cell-mediated immunity to sheep red blood cells (SRBC) in outbred Mai:NIH(S) mice [19].
• Limb reduction deformities in child exposed to isotretinoin in utero on gestation days 26-40 only [20].
• As rod photoreceptors are responsible for night vision, we administered isotretinoin to rats to learn whether night blindness resulted from rod cell death or from rod functional impairment [21].

Anatomical context of Vitamin A acid

• It is possible that a major mechanism of isotretinoin teratogenesis is a deleterious effect on cephalic neural-crest cell activity that results in the observed craniofacial, cardiac, and thymic malformations [22].
• The x-ray-induced chromatid damage in blood lymphocytes from a normal control was reduced significantly by cocultivation with blood or plasma from an XP patient receiving isotretinoin or by addition of 10(-6) M isotretinoin to cultures 1 h before x-irradiation [13].
• The active component of the acne drug Accutane is 13-cis-retinoic acid (RA), and it is highly teratogenic for the developing central nervous system [23].
• Rods and cones both showed slow recovery from bleach after isotretinoin in rats and in mice [21].
• We now describe a novel compound (E)-4-[3-(1-adamantyl)-4-hydroxyphenyl]-3-chlorocinnamic acid (3-Cl-AHPC/MM002) that induces apoptosis in the tRA-resistant leukemia cell lines M07e, KG-1, and HL-60R, and in tRA-resistant patient leukemic blasts [24].

Associations of Vitamin A acid with other chemical compounds

• After completion of surgery or radiotherapy (or both), these patients were randomly assigned to receive either isotretinoin (13-cis-retinoic acid) (50 to 100 mg per square meter of body-surface area per day) or placebo, to be taken daily for 12 months [2].
• HPLC analysis of ocular retinoids after isotretinoin and an intense bleach showed decreased levels of rhodopsin chromophore, 11-cis retinal, and the accumulation of the biosynthetic intermediates, 11-cis and all-trans retinyl esters [21].
• These p53 analyses were included in a prospective trial of the retinoid isotretinoin (1.5 mg/kg/day for 3 months) in 40 patients (45 oral premalignant lesions) [25].
• All-trans-retinoic acid (tRA) inhibited the proliferation of MBP-specific LNC in vitro [26].
• Vehicle-injected control rats were compared with rats treated with daily subcutaneous injections of 10 mg/kg body wt all-trans retinoic acid or 40 mg/kg body wt isotretinoin (n = 9 per group) either with a pretreatment (day -2 through 8) or posttreatment protocol (day +3 through 8), i.e., starting before or after induction of Thy-GN, respectively [27].

Gene context of Vitamin A acid

• However, the presence of a neutralizing Ab to IL-4 (11B11) during MBP-specific LNC activation in vitro did not reverse the inhibition of encephalitogenicity caused by tRA [26].
• Mean PAI-1 antigen and PAI activity in 9 a.m. plasma samples were non-significantly higher during isotretinoin than during placebo treatment [28].
• These data indicate that MMP and TIMP of epithelial origin may be involved in acne pathogenesis, and that isotretinoin-induced reduction in MMP-9 and -13 may contribute to the therapeutic effects of the agent in acne [29].
• Isotretinoin inhibited the arachidonic acid-induced secretion and mRNA expression of proMMP-2 and -9 in both cell types and of MMP-13 in HaCaT keratinocytes [29].
• Influence of aging, localization, glucocorticoids and isotretinoin on matrix metalloproteases 2 (MMP-2) and 9 (MMP-9) in suction blister fluids [30].

Analytical, diagnostic and therapeutic context of Vitamin A acid

• Isotretinoin was administered orally in single daily doses of 100 mg per square meter of body-surface area [12].
• Toxicity of isotretinoin in a chemoprevention trial to prevent second primary tumors following head and neck cancer [31].
• Elevated serum triglycerides, hyperostotic axial skeletal changes, and mucocutaneous reactions were more frequent in the group receiving isotretinoin than in the control group, and these differences were all statistically significant (P less than .001) [32].
• Isotretinoin blocked the formation of A2E biochemically and the accumulation of lipofuscin pigments by electron microscopy [33].
• We treated six patients with cutaneous T-cell lymphomas with isotretinoin 1 to 2 mg/kg/d. All patients experienced symptomatic relief (fading of skin lesions and disappearance of pruritus) within two to eight weeks of starting the drug therapy; pretreatment and posttreatment biopsy specimens were unchanged [34].

References