The authors propose a treatment to improve skin texture and to decrease thin wrinkles and creases. The treatment is based on the use of 0.1% all-trans retinoic acid intradermic injections (with biopresence of 0.02%) combined with topic cream, immediately followed by 340 Nm blue light skin exposure. These procedures determine ...

The effect of all-trans retinoic acid on the proliferation of essential fatty acid (EFA)-deficient and of EFA-supplemented adult human keratinocytes was investigated. EFA-deficient cell strains were supplied with one of four different fatty acid-supplemented media at the P0 to P1 passage. All-trans retinoic acid at 0.5 or 1.0 microM was ...

Hypervitaminosis A and D is a potential cause of "hyena disease" in cattle, which results from premature growth-plate closure in long bones of calves. This study showed that vitamin A induced growth-plate closure if calves were given an intramuscular injection of vitamins A and D (2,000,000 IU and 300,000 IU, ...

The cancer chemopreventive synthetic retinoid N-(4-hydroxyphenyl)retinamide (HPR) possesses antiproliferative and apoptotic activity at pharmacological doses. In this study we show that addition of antioxidants to HL-60 cells cultured in the presence of 3 microM HPR, markedly suppresses the apoptopic effect of the retinoid and significantly prolongs cell survival (48-96 h). ...

The proportion of mycolic acid containing trans-substituents at the proximal position of the meromycolate chain is an important determinant of fluidity of the mycobacterial cell wall and is directly related to the sensitivity of mycobacterial species to hydrophobic antibiotics. MMAS-1, an enzyme encoded in the gene cluster responsible for the ...

We have constructed dominant-negative retinoic acid receptors (RARs) by substituting single amino acid which has been found in a dominant-negative thyroid hormone receptor, and have expressed the dominant-negative RAR in the epidermis, a potential target organ of retinoic acid (RA). The resultant transgenic mice exhibited dramatic suppression of epidermal development, ...

The mammalian middle ear contains a chain of three ossicles, the malleus, incus, and stapes, that transmit into the inner ear the vibrations produced in the tympanic membrane by aerial sound. I show here that retinoic acid interferes with the formation of the middle ear in a stage-specific fashion. The ...

1. Rat hepatocytes cultured on a Matrigel matrix were exposed for 48 h to all-trans-retinoic acid, 9-cis-retinoic acid, 13-cis-retinoic acid or fenretinide. 2. Cytochrome P450 3A (CYP3A) RNA levels were increased by approximately eightfold in hepatocytes treated with the retinoids compared to control cultures. 3. CYP1A1 and CYP1A2 RNA levels ...

Photoisomerization of all-trans-retinoic acid and the geometrical isomers [9-cis-retinoic acid, 11-cis-retinoic acid, 13-cis-retinoic acid and 9,13-di-cis-retinoic acid] in ethanol and their biological effects on F9 teratocarcinoma cells were analyzed. The rates of photoisomerization of the retinoic acids illuminated by fluorescent lamps (1,200 lx) increased in inverse proportion to their concentrations. ...

Retinoic acid has pronounced effects on cultures of neoplastic cells. These have attracted the attention of pathologists, but it is important to note that much of the critical data about retinoic acid has been obtained from the current extension of our knowledge in the field of development. Some of these ...

BACKGROUND: The overall survival rate for patients with neuroblastoma has improved over the past two decades, but long-term survival for the subgroup of patients with high-risk disease remains low. In recent years, there has been interest in the potential clinical use of drugs able to induce differentiation of neuroblastoma cells. ...

Acitretin (Ro 10-1670, Neotigason), a second-generation monoaromatic retinoid, is the main acid derivative and active metabolite of etretinate (Ro 10-9359, Tigason). Three patients who were unresponsive to treatment with acitretin but who responded to etretinate are reported. Twenty-nine patients in the U.K. are currently receiving etretinate on a named-patient basis. ...

The ultra-structural development of synapses in retino-receptive layers of the opossum superior colliculus was studied by the ethanolic phosphotungstic acid (E-PTA) method. There was a tendency for a slight reduction in the diameter of synaptic disks, a rise and fall of numerical densities and, except for an ephemeral period, a ...

[3H]All-trans-retinoic acid has been shown to be an effective photoaffinity label for microsomal UDP-glucuronosyltransferases. Labeling of rat liver microsomal proteins with [3H]all-trans-retinoic acid and [32P]5-azido-UDP-glucuronic acid has shown that at least one protein in the 50-56 kDa mass range encompassing the UDP-glucuronosyltransferases photoincorporated both probes. The fraction of solubilized microsomal ...

A 28-kDa fragment (residues 178-423) of the human retinoic acid receptor gamma, hRARgamma D3E, encompassing the ligand-binding domain (LBD) was overproduced in Escherichia coli and purified as a monomer to more than 95% purity and homogeneity. The Kd for all-trans retinoic acid binding was 0.6 +/- 0.1 nM. Crystals of ...

To date, the clinical success of 13-cis or all-trans retinoic acid in the treatment of neuroblastoma has been disappointing. In vivo, 13-cis will isomerise to both all-trans and 9-cis retinoic acid, believed to be the main biologically-active isomers. In vitro studies with an N-type neuroblastoma cell line, SH SY 5Y, ...

The vitamin A metabolite retinoic acid plays an essential signaling role in spermatogenesis by acting as a ligand for nuclear retinoic acid receptors. However, little is known about the regulation of retinoic acid synthesis from vitamin A (retinol). Here we have examined mouse testis and epididymis for the presence of ...

The introduction of oral 13-cis-retinoic acid (isotretinoin, Roaccutane/Accutane) has been a key step in he history of dermatological treatments; it was and still is more than 15 years later the only compound which cures acne while oral antibiotics and other therapies, at best, have less dramatic effects. That oral isotretinoin ...

A novel butyric acid derivative, pivaloyloxymethyl butyrate, AN-9, was previously shown to be a potent differentiating agent. AN-9 exerts a significant anticancer activity in vitro and in vivo. In all the activities examined, AN-9 was more potent than butyric acid. Here we show that AN-9 and butyric acid induce cell ...

The tissue concentration of retinol and its metabolites was determined in a group of vitamin A deficient rats after a single dose of 53 micrograms of [11,12-3H]retinol. The sensitive technique of high performance liquid chromatography was used to analyse the metabolites of retinol. The analysis of the metabolites in tissues ...

Epidemiological studies have suggested an important immunomodulatory role for vitamin A and other related vitamin A compounds in adults and children. Although vitamin A is absorbed via the gastrointestinal tract, its affect on the gut mucosal immune cells has not been adequately investigated. We investigated the in-vitro effect of vitamin ...

We studied the effect of retinoic acid on the differentiation of cultured porcine preadipocytes. Porcine preadipocytes were cultured in serum-free medium (DME/F12 medium containing 100 nM insulin, 10 micrograms/mL transferrin, and 50 ng/mL hydrocortisone). Addition of increasing amounts of retinoic acid (1 nM to 20 microM) to the medium reduced ...

Lipoxygenase catalyzes the dioxygenation of polyenoic fatty acids such as linoleate and arachidonate. The aim of the present study was to examine the effect of retinol, all-trans-retinoic acid and 13-cis-retinoic acid on the activity of lipoxygenase-1 and lipoxygenase-2 towards linoleic acid. Lipoxygenase activity toward linoleic acid was followed by determining ...

Certain thiol-containing compounds catalyze, in a chemical reaction, the isomerization of 9-cis-retinoic acid to a mixture of all-trans-retinoic acid, 9-cis-retinoic acid, 13-cis-retinoic acid, and 9,13-dicis-retinoic acid. In the presence of such catalysts, all-trans-retinoic acid gives rise to the same mixture. Reactions approaching equilibrium contain more all-trans-retinoic acid than either of ...

In this study we have shown sex differences in endogenous retinoic acid synthesis and retinaldehyde dehydrogenase activity in the post-embryonic spinal cords of immature female and male G. a. affinis. The F9 reporter cell assay and the zymography bioassay showed that the endogenous retinoic acid levels correlated with the levels ...

Dietary supplementation with beta-carotene at 30 mg/day results in an increased serum trans-retinoic acid concentration in patients with a prior colonic polyp. In a number of human cell lines, trans-retinoic acid upregulates c-myc mRNA expression in colonic mucosa by reverse transcription polymerase chain reaction and correlated the results with serum ...

Liver bile salt-independent retinyl ester hydrolase (BSI-REH) has been suggested to play a significant role in the hydrolysis of chylomicron derived retinyl esters. Studies were conducted to investigate the individual effects of N-(4-hydroxyphenyl)retinamide (HPR), retinoic acid, 13-cis-retinoic acid, Acitretin and Temarotene on BSI-REH, serum retinol, and serum retinol-binding protein (RBP) ...

Application of exogenous retinoic acid (RA) to zebrafish during the initial stages of photoreceptor differentiation results in a precocious development of rod photoreceptors and an inhibition of cone photoreceptor maturation. The acceleration of rod differentiation is observed initially within the ventral retina 3 days after fertilization, following 24 hr of ...

Retinoic acid has both early or immediate (within hours) and late (after days) effects on gene expression. We studied the early effects of retinoic acid on the surfactant protein (SP) genes. Exposure of fetal rat lung explants to all trans-retinoic acid for 4 h resulted in a significant dose-dependent increase ...

Retinaldehyde, a natural metabolite of beta-carotene and retinol, has been proposed recently for topical use in humans. Because retinaldehyde does not bind to retinoid nuclear receptors, its biologic activity should result from enzymatic transformation by epidermal keratinocytes into ligands for these receptors, such as all-trans retinoic acid and 9-cis-retinoic acid. ...

All-trans-retinoic acid (all-trans-RA) and 13-cis-retinoic acid (13-cis-RA), due to their effects on cell differentiation, proliferation and angiogenesis, improved treatment results in some malignancies. Pharmacokinetic studies of all-trans-RA and 13-cis-RA along with monitoring of retinoic acid metabolites may help to optimize retinoic acid therapy and to develop new effective strategies for ...

The glutathione S-transferase (GST) activity towards 1-chloro-2,4-dinitrobenzene in intact human IGR-39 melanoma cells was determined by the quantification by HPLC-analysis of the excreted glutathione (GSH) conjugate (S-(2,4-dinitrophenyl)glutathione; DNPSG). The major GST subunit expressed in these melanoma cells is the pi-class GST subunit P1. Using this system, the effect of exposure ...

Retinoic acid has important actions on cell differentiation and osteoblastic function, and some of these actions may be mediated by changes in the insulin-like growth factor (IGF) axis. Skeletal cells synthesize IGF I and II and the six known IGF binding proteins (IGFBP). IGFBP-6 binds IGF II with high affinity ...

The influence of palmitic acid, 13-cis-retinoic acid, all-trans-retinoic acid, and all-trans-retinol on the activity of the human cholesteryl ester transfer protein (CETP) was evaluated either in total human plasma supplemented with a tracer dose of 3H-labeled cholesteryl-ester-containing high-density lipoprotein sub-fraction 3 ([3H]CE-HDL3), or in reconstituted mixtures containing [3H]CE-HDL3, isolated low-density ...

Even though retinoic acid can induce complete remissions in patients with acute promyelocytic leukemia, the duration of response is short and further therapy with this agent is less effective, suggesting the development of drug resistance. One possible way to overcome this problem is to use retinoic acid in combination with ...

The active form of vitamin D, 1 alpha,25-dihydroxyvitamin D3 (VD3), inhibits proliferation and induces differentiation of leukemia cells, but its clinical use is limited by the adverse effect of hypercalcemia. In this study we found that the loop diuretic ethacrynic acid, which is used to treat hypercalcemia, enhanced the differentiation ...

A gradient reversed-phase high-performance liquid chromatographic technique is described for the easy separation and quantification of some retinoids; all-trans-retinoic acid, 13-cis-retinoic acid, 9-cis-retinoic acid and their corresponding 4-oxometabolites, in plasma. The method involved a diethyl ether-ethyl acetate (50:50, v/v) mixture extraction at pH 7 with acitretin and 13-cis-acitretin as internal ...

An inducible cytochrome P-450 (P-450) catalyzing retinoic acid synthesis was purified from liver microsomes of 3-methylcholanthrene (3-MC)-treated rats, based on the activity of all-trans-retinoic acid formation from all-trans-retinal. We previously reported that the retinoic acid synthesis by microsomes was catalyzed by a cytochrome P-450-linked monooxygenase system (Tomita et al. (1993) ...

We observed that retinoic acid, which differentiates the human neuroblastoma SK-N-BE into mature neurons, induced an elevation in levels of polyunsaturated fatty acids, especially arachidonic acid (20:4 n-6). This effect was not induced by phorbol myristate acetate, another differentiating agent. We then explored the effects of retinoic acid on the ...

Metabolic inactivation of all-trans retinoic acid to 4-hydroxy retinoic acid occurs via a cytochrome P-450 enzyme. We investigated the effects of liarozole on the retinoic acid 4-hydroxylase activity of human epidermis and its ability to modify in vivo human skin responses to retinoic acid and all-trans retinol. Retinoic acid 4-hydroxylase ...

Vitamin A, all-trans-retinol, is metabolized to retinoic acid in vivo by a tightly controlled two-step conversion. Retinoic acid then binds to nuclear receptors and modulates cellular proliferation and differentiation. Because only a small fraction of retinol applied topically can be metabolized to retinoic acid, alternative pathways of retinol metabolism in ...

BACKGROUND: Patients with retinitis pigmentosa have been suggested to benefit from treatment with moderate doses of retinyl palmitate. Retinyl palmitate is not an active retinoid in itself but is metabolised to active components in the body. To find out which metabolites of retinyl palmitate were formed and at which concentrations, ...

The effects of retinoids on a regenerating urodele limb make them interesting candidates for endogenous ligands during regeneration. We review the evidence for considering this possibility. This includes analysis of retinoids and retinoic acid receptors in the regenerate, and studies on activation of retinoid reporter genes. Recent work has provided ...

RXR is a nuclear receptor that plays a central role in cell signaling by pairing with a host of other receptors. Previously, 9-cis-retinoic acid (9cRA) was defined as a potent RXR activator. Here we describe a unique RXR effector identified from organic extracts of bovine serum by following RXR-dependent transcriptional ...

Retinoic acid receptor (RAR) active retinoids have proven therapeutically useful for treating certain cancers and dermatological diseases. Herein, we describe the discovery of two new RAR active trienoic acid retinoids, (2E,4E,6E)-7-(3,5-di-tert-butylphenyl)-3-methylocta-2, 4,6-trienoic acid (10a, ALRT1550) and (2E,4E,6Z)-7-(3,5-di-tert-butylphenyl)-3-methylocta-2, 4,6-trienoic acid (10b, LG100567). ALRT1550 is a RAR selective retinoid which exhibits exceptional ...

Acute promyelocytic leukemia (APL) is associated with a chromosomal translocation t(15;17) and successfully differentiated by all-trans-retinoic acid (ATRA) in vivo as well as in vitro. The PML-retinoic acid receptor alpha (RARA) oncoprotein, which is generated by the translocation, blocks the differentiation, and ATRA is thought to modulate the dominant negative ...

We studied the enzymatic characteristics of the oxidative catabolism of retinoic acid (RA) and its inhibition by liarozole-fumarate in homogenates of rat Dunning R3327G prostate tumors. Homogenates of rat liver were used as reference material. Both tumor and liver homogenates were able to catabolize retinoic acid. HPLC analysis revealed only ...

In this report, we describe an auto-regulatory loop in human keratinocytes, whereby all-trans retinoic acid (retinoic acid) regulates its own biosynthesis from all-trans retinol (retinol) through regulation of retinol esterification. Retinol esterification activity was low in normal proliferating human keratinocytes, cultured in retinoid-free media. Treatment of keratinocytes with retinoic acid ...

It has been previously demonstrated that vitamin A-deficient rats supplemented with retinoic acid cannot complete gestation. Resorption of fetuses invariably occurs in these animals beginning Day 15 of gestation. Retinol must be administered on or before Day 10 of gestation in order to prevent this phenomenon. The administration of as ...

This study reports a morphological, skeletal, and molecular characterization of the supernumerary limbs induced by systemic administration of all-trans retinoic acid to egg-cylinder stage mouse embryos. As initially described by Rutledge et al. (Proc. Natl. Acad. Sci. USA 91, 5436, 1994), we have found that oral administration of all-trans retinoic ...