Disease relevance of retinol

• Vitamin A transport in human vitamin A toxicity [1].
• Night blindness in Sorsby's fundus dystrophy reversed by vitamin A [2].
• We studied the relation of serum vitamin A (retinol), beta-carotene, vitamin E, and selenium to the risk of lung cancer, using serum that had been collected during a large blood-collection study performed in Washington County, Maryland, in 1974 [3].
• The significant inverse association of vitamin A intake with the risk of breast cancer was also found on study of data based on the 1984 questionnaire and four years of follow-up [4].
• Overall, 1 additional infant survived without chronic lung disease for every 14 to 15 infants who received vitamin A supplements [5].
• High intakes of vitamin A, retinol, and provitamin A carotenoids may reduce the risk of gastric cancer [6].
• These data suggest that excessive intake of vitamin A may increase the risk or severity of asthma in industrialized countries whereas vitamin A deficiency continues to increase mortality from infectious diseases in developing countries [7].

Psychiatry related information on retinol

• Vitamin A supplementation for extremely-low-birth-weight infants. National Institute of Child Health and Human Development Neonatal Research Network [5].
• Vitamin A intoxication as a consequence of megavitamin therapy for minimal brain dysfunction occurred in a 4-year-old boy [8].
• After alcohol consumption, the number of lipocytes (as assessed by light microscopy) was significantly decreased in fatty livers and at various stages of hepatic fibrosis; this was associated with a decreased hepatic vitamin A content [9].
• The hypothesis of this article is that late onset Alzheimer's disease (AD) is influenced by the availability in brain of retinoic acid (RA), the final product of the vitamin A (retinoid) metabolic cascade [10].
• Circulating concentrations of magnesium, zinc, vitamin A, and alpha- and beta-carotene were measured, and food preferences were assessed by questionnaire [11].

High impact information on retinol

• Apoptosis induced by vitamin A signaling is crucial for connecting the ureters to the bladder [12].
• We show that the common nephric duct does not differentiate into the trigone but instead undergoes apoptosis, a crucial step for ureter transposition controlled by vitamin A-induced signals from the primitive bladder [12].
• Rara(-/-) Rarb2(-/-) mice display impaired vitamin A signaling and develop syndromic urogenital malformations similar to those that occur in humans, including renal hypoplasia, hydronephrosis and mega-ureter, abnormalities also seen in mice with mutations in the proto-oncogene Ret [13].
• Here we show that a single maternal administration of a low dose of the vitamin A metabolite retinoic acid is sufficient to compensate the requirement for Hoxa1 function [14].
• Our studies indicate the presence of a new reciprocal signaling loop between the ureteric bud epithelium and the stromal mesenchyme, dependent on Ret and vitamin A. In the first part of the loop, vitamin-A-dependent signals secreted by stromal cells control Ret expression in the ureteric bud [15].

Chemical compound and disease context of retinol

• These limited clinical data support conclusions from detailed studies with hypervitaminotic rats, which suggest that vitamin A toxicity occurs when excessive amounts of vitamin A are presented to cell membranes in association with plasma lipoproteins, rather than specifically bound to retinol-binding protein [1].
• Retinoic acid (RA), an analogue of vitamin A, has been shown to inhibit neuroblastoma cell growth and clonability in soft agar, and to induce extensive neurite outgrowth [16].
• These include occasional adverse lipid changes, potential for bleeding and vitamin E deficiency, and, with some preparations, vitamin A and D toxicity [17].
• A reduced risk of rectal cancer was associated with vitamin C but not with vitamin A. The increased risk associated with high protein and total energy was confined to those consuming a low fiber diet, particularly among women; but some other aspects of the relationship between fiber consumption and risk of colorectal cancer were more complex [18].
• Nonspecific and unregulated delivery of retinoids to biologic membranes apparently leads to vitamin A (retinoid) toxicity [19].

Biological context of retinol

• The regular provision of a supplement of vitamin A to children, at a level potentially obtainable from foods, in an area where vitamin A deficiency and under-nutrition are documented public health problems contributed substantially to children's survival; mortality was reduced on average by 54 percent [20].
• Using a smoothed regression curve, we found an apparent threshold near 10,000 IU per day of supplemental vitamin A. The increased frequency of defects was concentrated among the babies born to women who had consumed high levels of vitamin A before the seventh week of gestation [21].
• Severe vitamin A deprivation in rodents results in maternal infertility, precluding a thorough investigation of the role of RA during embryogenesis [22].
• The mean birth weight was 770 g in the vitamin A group and 769 g in the control group, and the respective gestational ages were 26.8 and 26.7 weeks [5].
• Distal ureter morphogenesis depends on epithelial cell remodeling mediated by vitamin A and Ret [13].

Anatomical context of retinol

• Nutritional night blindness is thus part of the pathophysiology of this genetic disease and vitamin A supplementation can lead to dramatic restoration of photoreceptor function [2].
• Regulation of terminal differentiation of cultured human keratinocytes by vitamin A [23].
• Mutation of RPE65 can cause severe blindness from birth or early childhood, and RPE65 protein is associated with retinal pigment epithelium (RPE) vitamin A metabolism [24].
• This paper reports the effect of vitamin A and its derivatives, the retinoids, on plasminogen activator (PA) synthesis in chick embryo fibroblast cultures (CEF) [25].
• These results identify a temporal window of susceptibility to retinoids that is critical for mammalian inner ear specification, and provide the first evidence that a subteratogenic dose of vitamin A derivative can be effective in rescuing a congenital defect in the mammalian embryo [14].

Associations of retinol with other chemical compounds

• The proportion of infants with serum retinol values below 20 microg per deciliter (0.70 micromol per liter) was lower in the vitamin A group than in the control group (25 percent vs. 54 percent, P<0.001) [5].
• We present evidence that the vitamin D response element in the human osteocalcin gene confers responsiveness to the vitamin A metabolite, retinoic acid [26].
• The discovery of this new RX response element provides a means for distinguishing between the two retinoid receptor systems and suggests that an RXR-mediated pathway exists for modulating vitamin A metabolism [27].
• Membranes as the energy source in the endergonic transformation of vitamin A to 11-cis-retinol [28].
• Steroid and thyroid hormones and vitamin A metabolites (retinoids) regulate the expression of complex gene programs by binding to members of the nuclear receptor family of ligand-activated transcription factors [29].
• According to these findings, the equivalent of 1 microg retinol would be 12 microg beta-carotene (95% CI: 8, 22 microg) for fruit and 28 microg beta-carotene (17, 84 microg) for green leafy vegetables [30].

Gene context of retinol

• These malformations belong to the fetal vitamin A deficiency syndrome, supporting the idea that RXR alpha is involved in retinoid signaling in vivo [31].
• Vitamin A controls epithelial/mesenchymal interactions through Ret expression [15].
• In contrast to other genes whose defects have been implicated in degenerative retinopathies, RPE65 is the first disease gene in this group of inherited disorders that is expressed exclusively in the RPE, and may play a role in vitamin-A metabolism of the retina [32].
• In a SFD family with a novel TIMP3 point mutation, we tested a hypothesis that their night blindness is due to a chronic deprivation of vitamin A at the level of the photoreceptors caused by a thickened membrane barrier between the photoreceptor layer and its blood supply [2].
• These results suggest two vitamin A-mediated regulation steps in IFN-gamma gene expression: positive regulation of IFN-gamma transcript levels, and negative regulation posttranscriptionally [33].
• We demonstrate that SANTA MARIA functions upstream of vitamin A formation in neurons and glia, which are outside of the retina [34].

Analytical, diagnostic and therapeutic context of retinol

• RESULTS: By 36 weeks' postmenstrual age, 59 of the 405 infants (15 percent) in the vitamin A group and 55 of the 402 infants (14 percent) in the control group had died [5].
• Activity of vitamin A analogues in cell cultures of mouse epidermis and organ cultures of hamster trachea [35].
• Limbs generated at site of tail amputation in marbled balloon frog after vitamin A treatment [36].
• Surveillance data were used to institute changes in public health management including measles vaccination, vitamin A supplementation, and control programs for diarrhea and acute respiratory infections and to ensure rapid responses to cholera, Shigella dysentery, and meningoencephalitis [37].
• Vitamin A supplementation and child mortality. A meta-analysis [38].

References