isotretinoin and Body-Weight

Background: Retinoids, which include isotretinoin, reduce sebum levels, the degree of epidermal wetness (CORN) and cause an increase in transepidermal water loss (TEWL). Weight gain has also been observed in isotretinoin-treated patients. An agent that can reduce the severity of isotretinoin side effects is evening primrose oil (Oenothera paradoxa). The purpose of this study was to evaluate the effect of evening primrose oil supplementation in patients with acne vulgaris treated with isotretinoin on skin hydration status (CORN), transepidermal water loss (TEWL), skin oiliness (sebum) and changes in body weight and BMI. Methods: Patients diagnosed with acne were assigned to the isotretinoin-treated group (n = 25) or the isotretinoin and evening primrose oil-treated group (n = 25). The intervention lasted 9 months. CORN (with a corneometer), TEWL (with a tewameter) and sebum (with a sebumeter) were assessed twice, as well as body weight and BMI (Tanita MC-780). Results: The isotretinoin-treated group showed statistically significant reductions in CORN (p = 0.015), TEWL (p = 0.004) and sebum (p < 0.001) after the intervention. In the group treated with isotretinoin and evening primrose oil, TEWL and sebum levels also decreased significantly (p < 0.05), while CORN levels increased from 42.0 ± 9.70 to 50.9 ± 10.4 (p = 0.017). A significant decrease in body weight (p < 0.001) and BMI (p < 0.001) was observed in both groups after 9 months of intervention. Conclusions: During isotretinoin treatment, supplementation with evening primrose oil increased skin hydration. However, there were no differences between groups in transepidermal water loss, skin oiliness, weight loss and BMI.

Topics: Acne Vulgaris; Body Weight; Dietary Supplements; gamma-Linolenic Acid; Humans; Isotretinoin; Linoleic Acids; Oenothera biennis; Plant Oils; Skin; Water

Acne is an important health issue with a major psychological impact in addition to the physical problems it causes.. To investigate the superiority of mobile teledermatology in the care of patients with high-need facial acne in comparison to outpatient services with particular attention to treatment efficacy, safety, and patient compliance. Further, patient satisfaction with remote care was evaluated.. Sixty-nine consecutive patients (f: 25, m: 44, median age: 19 years, range: 13-37 years) were randomly allocated to either the teleconsultation (TCA) or the outpatient consultation (OCA) arm of the trial to receive isotretinoin treatment in weight and severity-dependent dosages over 24 weeks. Acne grading was performed by one examiner using the Global Acne Severity Scale (GEA) and the total lesion counting (TLC).. Due to noncompliance issues, 17 of 69 (24.6%) patients were excluded from the study, of who 10 had been assigned to the TCA (10/34; 29.4%) and 7 to the OCA (7/35; 20%). Both, in the TCA (GEA-score: ∆ = 2.25; TLC: ∆ = 89.08) and in the OCA (GEA-score: ∆ = 2.0; TLC: ∆ = 91.21) excellent and almost equivalent therapeutic outcomes were achieved. In the TCA, however, less patients experienced adverse reactions (P = 0.55). Even though additional live supervision would have been appreciated in some teledermatology cases, patients were satisfied with the mobile service and no consultation request was created.. Mobile teledermatology is an efficient, safe and well-accepted tool among patients with high-need acne constituting at least a valuable adjunct to outpatient care services. Further larger studies would be useful to confirm our findings.

Topics: Acne Vulgaris; Adolescent; Adult; Ambulatory Care; Body Weight; Dermatologic Agents; Facial Dermatoses; Female; Humans; Isotretinoin; Male; Patient Satisfaction; Severity of Illness Index; Telemedicine; Young Adult

To investigate the feasibility of adaptive dosing and the impact of pharmacogenetic variation on 13-cis-retinoic acid (13-cisRA) disposition in high-risk patients with neuroblastoma.. 13-cisRA (160 mg/m(2) or 5.33 mg/kg/d) was administered to 103 patients ages 21 years or less and plasma concentrations of 13-cisRA and 4-oxo-13-cisRA quantitated on day 14 of treatment. Seventy-one patients were recruited to a dose adjustment group, targeting a 13-cisRA C(max) of 2 μmol/L, with dose increases of 25% to 50% implemented for patients with C(max) values less than 2 μmol/L. A population pharmacokinetic model was applied and polymorphisms in relevant cytochrome P450 genes analyzed.. 13-cisRA C(max) values ranged from 0.42 to 11.2 μmol/L, with 34 of 103 (33%) patients failing to achieve a C(max) more than 2 μmol/L. Dose increases carried out in 20 patients in the dose adjustment study group led to concentrations more than 2 μmol/L in 18 patients (90%). Eight of 11 (73%) patients less than 12 kg, receiving a dose of 5.33 mg/kg, failed to achieve a C(max) of 2 μmol/L or more. Significantly, lower C(max) values were observed for patients treated with 5.33 mg/kg versus 160 mg/m(2) (1.9 ± 1.2 vs. 3.1 ± 2.0 μmol/L; mean ± SD; P = 0.023). C(max) was higher in patients who swallowed 13-cisRA capsules as compared with receiving the drug extracted from capsules (4.0 ± 2.2 vs. 2.6 ± 1.8 μmol/L; P = 0.0012). The target C(max) was achieved by 93% (25/27) versus 55% (42/76) of patients in these 2 groups, respectively. No clear relationships were found between genetic variants and 13-cisRA pharmacokinetic parameters.. Dosing regimen and method of administration have a marked influence on 13-cisRA plasma concentrations. Body weight-based dosing should not be implemented for children less than 12 kg and pharmacologic data support higher doses for children unable to swallow 13-cisRA capsules.

Topics: Adolescent; Antineoplastic Agents; Body Weight; Child; Child, Preschool; Cytochrome P-450 Enzyme System; Female; Genotype; Humans; Infant; Infant, Newborn; Isotretinoin; Male; Neuroblastoma; Treatment Outcome

and Purpose: Inflammatory Bowel Disease (IBD) is a persistent bio-psychological disorder with the absence of actual pathological reason. Association between IBD and isotretinoin has been reported by many human and in vitro studies. However, in this study, our focus is on finding the causal relationship between IBD and isotretinoin for the development of a new animal model.. Twenty-eight Sprague Dawley rats were taken for this study and divided into five groups (i.e. Group 1: Normal control, Group 2: Standard IBD Model Group (Indomethacin treated), Group 3: Isotretinoin low dose (7 mg/kg), Group 4: Isotretinoin medium dose (35 mg/kg), Group 5: Isotretinoin high dose (70 mg/kg). The rats were treated according to assigned treatment and observed on different days to evaluate the severity of IBD with the help of symptomatical (nausea, diarrhea, stool consistency, etc.) activity, biochemical parameters, macroscopy, and histological analyses.. During the entire study period, body weight, stool consistency and frequency of the animals had been observed daily. No significant reduction in body weight was observed between the disease induced and normal control animals; however, it was observed that the stool consistency of the animals became less (mucus in stool) day by day and stool frequency increased (frequent defecation) in the different isotretinoin groups compared to the control group. There was statistically significant increase in TBARS levels of isotretinoin low (p < 0.05), medium (p < 0.001) and high dose (p < 0.01) treated group was observed, as compared to control group. Similarly, statistically significant effects of isotretinoin on GSH level (p < 0.01), CAT activity (p < 0.01), and SOD (p < 0.01) were also observed. Increase in TNF-α levels found significantly higher in isotretinoin medium dose (35 mg/kg) treated group (p < 0.001) as compared with control group as well as standard IBD model group. All the three-isotretinoin treated groups (Isotretinoin low dose: p < 0.001; Isotretinoin medium dose: p < 0.001; Isotretinoin high dose: p < 0.001) depicted significant difference in macroscopic scores as compared with control group; these results are comparable with standard IBD model group. Histological analyses revealed that, among three-dose groups of isotretinoin, there was excessive amount of crypt abscesses, infiltration of inflammatory cells, and formation of ulceration observed in isotretinoin medium dose treated group.. As standard indomethacin treated group, isotretinoin also caused significant damage to intestinal mucosa, and form ulceration in gastrointestinal tract. Compared to control group, isotretinoin significantly worsens the disease condition, which were comparable to the indomethacin-treated group; however, isotretinoin at the dose of 35 mg/kg caused maximum severe damage to the intestinal mucosa.

Topics: Animals; Body Weight; Humans; Indomethacin; Inflammatory Bowel Diseases; Isotretinoin; Rats; Rats, Sprague-Dawley

Hidradenitis suppurativa (HS) is a disease characterized by the development of painful, deep-seeded nodules and abscesses. Treatment guidelines include a combination of lifestyle, surgical, and medical interventions. Isotretinoin has not been included in the treatment guidelines due to the limited number of studies and conflicting reports of efficacy.. The purpose of this study is to evaluate the clinical response to isotretinoin in HS patients and to determine whether there is a particular patient population that may benefit more from this treatment.. A retrospective chart review was conducted on all HS patients treated with isotretinoin within the years of 2014-2016. Sex, age, weight, history of acne, Hurley stage, and treatment dose and duration were extracted from patient charts.. Of the 25 patients included in the study, 32% (8/25) had no response, 32% (8/26) showed partial response, and 36% (9/25) demonstrated complete response to isotretinoin treatment. Complete response was seen only in Hurley stage I and II patients. Hurley III patients made up 50% of the non-responders. Those with any sort of treatment response were more likely to be female, younger, weigh less, and have a higher prevalence of acne compared to non-responders.. This is a retrospective chart review with a small sample size of 25 patients.. Physicians should consider isotretinoin as a potential treatment for HS, as it may be beneficial in patients with mild and moderate disease and patients who are female, younger, weigh less, and have a personal history of acne.

Topics: Acne Vulgaris; Adolescent; Adult; Age Factors; Body Weight; Dermatologic Agents; Female; Hidradenitis Suppurativa; Humans; Isotretinoin; Male; Middle Aged; Retrospective Studies; Severity of Illness Index; Sex Factors; Treatment Outcome; Young Adult

Isotretinoin (ISO, 13-cis-retinoic acid) is commonly prescribed as Accutane for the treatment of acne. ISO is a known teratogen and the physical side effects of the drug have been well documented. However, possible psychological risks associated with the drug have yet to be determined. Retinoid receptors are abundant in the striatum and hippocampus, brain structures involved in implicit and explicit memory processes, respectively. The current study examined whether ISO influenced implicit or explicit memory processes using a two-stage radial-arm maze (RAM) task. The two stages were identical, except for the method of presenting arm choices to the rats: one at a time (Stage 1) or in pairs (Stage 2). Male rats (n=12/group) were tested on both stages of the RAM during chronic oral treatment with ISO (0, 5, 10, or 15 mg/kg/day). Performance indicated that ISO impaired explicit memory in Stage 2, but retention tests one month after ISO exposure ended, indicated recovery from this explicit memory impairment and evidence of enhanced implicit memory in the 10 mg and 15 mg ISO rats. These data indicate extensive, enduring memory effects from oral ISO treatment at doses likely to produce serum levels within the range typically used to treat acne in humans.

Topics: Animals; Anxiety; Behavior, Animal; Body Weight; Discrimination Learning; Isotretinoin; Learning; Male; Maze Learning; Memory; Psychomotor Performance; Rats; Rats, Long-Evans

Oral treatment with the anti-acne drug Accutane (isotretinoin, 13-cis-retinoic acid) has been associated with suicide ideation and depression. Here, depression-like behaviors (i.e., behavioral despair and anhedonia) were quantified in adult Sprague-Dawley rats gavaged daily beginning at postnatal day (PND) 82 with 13-cis-RA (7.5 or 22.5 mg/kg) or all-trans-retinoic acid (10 or 15 mg/kg ). Tested at PND 130-131 in the Forced Swim Test, 7.5 mg/kg 13-cis-RA marginally decreased immobility and slightly increased climb/struggle durations whereas neither all-trans-retinoic acid group differed from controls. Voluntary saccharin solution (0.03%) intake at PND 102-104 and PND 151-153 was not different from controls in any treated group, although all RA-treated groups had lower intakes. Swim speed in a water maze at PND 180 was similar across groups, indicating no RA-induced differences in physical ability. Open field activity was mildly decreased at PND 91 in 7.5 mg/kg-treated males only, but it was within the control range at PND 119, 147, and 175. Thus, at serum levels similar to those in humans receiving the drug, chronic 13-cis-RA treatment did not severely affect depression-like behaviors in rats. These data do not substantiate the hypothesis of 13-cis-RA-induced depression.

Topics: Aging; Animals; Behavior, Animal; Body Weight; Depression; Dose-Response Relationship, Drug; Drinking; Eating; Female; Isotretinoin; Keratolytic Agents; Male; Motor Activity; Rats; Saccharin; Sex Characteristics; Sweetening Agents; Swimming; Tretinoin

Administration of 13-cis retinoic acid (isotretinoin) for acne is occasionally accompanied by hyperlipidemia. It is not known why some persons develop this side effect.. To determine whether isotretinoin triggers a familial susceptibility to hyperlipidemia and the metabolic syndrome.. Cross-sectional comparison.. University hospital in Lausanne, Switzerland.. 102 persons in whom triglyceride levels increased at least 1.0 mmol/L (> or =89 mg/dL) (hyperresponders) and 100 persons in whom triglyceride levels changed 0.1 mmol/L (< or =9 mg/dL) or less (nonresponders) during isotretinoin therapy for acne. Parents of 71 hyperresponders and 60 nonresponders were also evaluated.. Waist-to-hip ratio; fasting glucose, insulin, and lipid levels; and apoE genotype.. Hyperresponders and nonresponders had similar pretreatment body weight and plasma lipid levels. When reevaluated approximately 4 years after completion of isotretinoin therapy, hyperresponders were more likely to have hypertriglyceridemia (triglyceride level > 2.0 mmol/L [>177 mg/dL]; odds ratio [OR], 4.8 [95% CI, 1.6 to 13.8]), hypercholesterolemia (cholesterol level > 6.5 mmol/L [>252 mg/dL]; OR, 9.1 [CI, 1.9 to 43]), truncal obesity (waist-to-hip ratio > 0.90 [OR, 11.0 (CI, 2.0 to 59]), and hyperinsulinemia (insulin-glucose ratio > 7.2; OR, 3.0 [CI, 1.6 to 5.7]). In addition, more hyperresponders had at least one parent with hypertriglyceridemia (OR, 2.6 [CI, 1.2 to 5.7]) or a ratio of total to high-density lipoprotein cholesterol that exceeded 4.0 (OR, 3.5 [CI, 1.5 to 8.0]). Lipid response to isotretinoin was closely associated with the apoE gene.. Persons who develop hypertriglyceridemia during isotretinoin therapy for acne, as well as their parents, are at increased risk for future hyperlipidemia and the metabolic syndrome.

Topics: Acne Vulgaris; Adolescent; Adult; Apolipoproteins E; Body Weight; Cross-Sectional Studies; Dermatologic Agents; Female; Genetic Predisposition to Disease; Genotype; Glucose Tolerance Test; Humans; Hyperlipidemias; Insulin; Isotretinoin; Lipids; Male; Metabolic Syndrome; Middle Aged; Pharmacogenetics; Retrospective Studies; Risk Factors

Topics: Acne Vulgaris; Adolescent; Adult; Apolipoproteins E; Body Weight; Cross-Sectional Studies; Dermatologic Agents; Female; Genetic Predisposition to Disease; Genotype; Glucose Tolerance Test; Humans; Hyperlipidemias; Insulin; Isotretinoin; Lipids; Male; Metabolic Syndrome; Middle Aged; Pharmacogenetics; Retrospective Studies; Risk Factors

Neuroblastoma, a childhood tumour of the sympathetic nervous system, may undergo spontaneous differentiation or regression due to apoptosis after no or minimal therapy. However, the majority of neuroblastomas are diagnosed as metastatic tumours with a poor prognosis in spite of intensive multimodal therapy. Vitamin A and its analogues (retinoic acid, RA) play an important role in normal cel lular differentiation and programmed cell death. RA regulates neuroblastoma growth and differentiation in vitro, and has shown activity against human neuroblastoma in vivo.. Recently, 9-cis RA was shown to induce apoptosis in vitro in neuroblastoma using a 5 days short-term treatment and subsequent washout. In the present study, nude rats with human neuroblastoma SH-SY5Y xenografts were treated with 13-cis RA (4 mg po daily), 9-cis RA (5 mg po daily) or the novel analogue Ro 13-6307 (0.3 mg po daily) using either a continuous or short-term schedule.. ALL three different retinoids decreased neuroblastoma growth significantly in terms of tumour weight after 8-12 days when compared to untreated controls (P < 0.05). Minor signs of toxicity in 13-cis RA treated rats were observed. However, severe toxicity with significant weight loss was seen in all rats treated with 9-cis RA and Ro 13-6307. Toxicity was more pronounced with the continuous regimen.. We conclude that different retinoids reduce neuroblastoma tumour growth in vivo. Drug scheduling and dosage may affect both therapeutic efficacy and toxic side effects. Further in vivo studies are warranted, including pharmacokinetic and molecular analyses, before clinical trials with promising retinoids like 9-cis RA and Ro 13-6307 can be started in children with neuroblastoma.

Topics: Alitretinoin; Animals; Antineoplastic Agents; Body Weight; Cell Differentiation; Cell Division; Diarrhea; Drug Administration Schedule; Fatty Acids, Unsaturated; Female; Humans; Isotretinoin; Male; Mice; Neoplasm Transplantation; Neuroblastoma; Rats; Rats, Nude; Tretinoin; Tumor Cells, Cultured; Xenograft Model Antitumor Assays

Retinoids, derivatives of vitamin A, have strong anti-inflammatory and antiproliferative properties. We previously demonstrated that the pan-agonists all-transretinoic acid (RA) and isotretinoin (13-cis RA) alleviate renal damage in rat acute glomerulonephritis (GN) induced by anti-Thy-1.1 mAb OX-7.. The present study examined the effects of low dose and high dose treatment with isotretinoin in the chronic glomerulonephritis model, Thy-GN. Thy-GN was induced by a single intravenous injection of monoclonal antibody (mAb) 1-22-3 in uninephrectomized Wistar rats (N = 7 to 10 per group). Control and nephritic groups were treated with vehicle (veh), low dose isotretinoin (2 mg/kg body wt), or high dose isotretinoin (10 mg/kg body wt). The experiment was terminated 60 days after induction of Thy-GN.. In animals with Thy-GN, isotretinoin abrogated the increase in blood pressure and significantly reduced albuminuria. Glomerulosclerosis index, glomerular and interstitial cell counts, as well as the area of the interstitial space were significantly lower in nephritic rats treated with low and high dose isotretinoin compared to vehicle-treated nephritic controls. Treatment with isotretinoin also significantly reduced the number of glomerular and interstitial macrophages. The increase of transforming growth factor (TGF)-beta1, TGF receptor II and prepro-endothelin-1 gene expression in vehicle-treated nephritic rats was significantly attenuated by isotretinoin.. Treatment with isotretinoin significantly reduces glomerular and interstitial damage in rats with chronic glomerulonephritis as indicated by different functional and histological markers. Retinoids may provide a novel therapeutic option for the treatment of glomerulonephritis.

Topics: Albuminuria; Animals; Blood Pressure; Body Weight; Chronic Disease; Collagen Type I; Creatinine; Fibronectins; Gene Expression; Glomerulonephritis; Isotretinoin; Kidney; Kidney Glomerulus; Kidney Tubules; Male; Rats; Rats, Wistar

The teratogenicity of 13-cis-retinoic acid (RA) either administered alone or following pretreatment with phenobarbital sodium (PB), was assessed. Groups of gravid CF-1 mice were administered dosages of either 10, 100, 200, or 400 mg/kg of RA orally on either days 11, 12 or 13 of gestation, in order to determine structural alterations. In addition, separate groups of mice were orally pretreated with 80 mg/kg/day of PB on days 7 through 10 of gestation prior to the administration of RA. Skeletal alterations attributed to maternal administration of either 100, 200 or 400 mg/kg of RA on days 11-13 included delayed ossification of the limbs and supraoccipital bone, the presence of extra ribs, and various sternebral defects. Soft tissue alterations included cleft palate and dilation of the renal pelves which occurred following maternal exposure on days 11 and 12-13, respectively. Significant decreases in the incidence of cleft palate and delayed ossification of the limbs were observed in those dams administered RA on days 11 or 12, respectively, following prior treatment with PB. These data suggest that administration of PB, a prototypical hepatic microsomal enzyme inducer, may partially antagonize the teratogenicity of RA.

Topics: Abnormalities, Drug-Induced; Administration, Oral; Animals; Animals, Newborn; Body Weight; Bone and Bones; Cleft Palate; Female; Isotretinoin; Male; Mice; Organ Size; Osteogenesis; Phenobarbital

The effect of administration of 13-cis-retinoic acid (100 mg/kg diet) on lipid metabolism was examined in male rats fed either a 20% casein + 0.3% methionine diet, a 20% casein diet, a 10% casein + 0.3% methionine diet, or a 10% casein + 0.6% methionine diet for 10 days. Hepatic triglyceride concentrations of rats fed either 10% casein diet were 3-fold greater than animals receiving diets containing 20% casein. The addition of 13-cis-retinoic acid to the diet further increased the total hepatic lipid (43-56%) and triglyceride (approximately 2-fold) concentrations in rats fed the 10% casein diets. 13-cis-Retinoic acid supplementation did not alter the total liver lipid or triglyceride concentrations in rats fed either of the 20% casein diets. Thus, under specific dietary conditions, the administration of 13-cis-retinoic acid resulted in a marked accumulation of hepatic lipids which did not appear to be related to the total methionine content of the diet nor to the hepatic concentrations of S-adenosylmethionine and glutathione. In addition, all four groups of 13-cis-retinoic acid-fed rats exhibited elevations in the concentration of serum triglycerides, and 10-20% reductions in serum cholesterol concentrations.

Topics: Animals; Body Weight; Cholesterol; Diet; Fatty Liver; Isotretinoin; Male; Organ Size; Rats; Rats, Sprague-Dawley; Triglycerides

Isotretinoin (13-cis-RA) is known to be teratogenic in humans and laboratory animals. The relatively low potency of 13-cis-RA in NRMI mice in comparison to the all-trans isomer has been proposed to be due to minimal transfer across the placenta (Creech-Kraft et al., '87). To further delineate the teratogenic potential of 13-cis-RA, a dose-response, temporal study was conducted in vivo and in vitro using submerged limb culture and image analysis evaluation of development. Dose-dependent embryotoxicity was produced by treatment on GD 7, while later treatments produced inconsistent effects on resorption rate and fetal weight. Treatment on either GD 7 or GD 8 produced a number of malformations in dose-dependent manner. Most common were tail and cleft palate defects, which were produced by 13-cis-RA on each of the days tested (GD 7-GD 11), with peak malformations occurring on GD 9 and GD 10 for tail and cleft palate, respectively. Most limb defects were produced after GD 10 and GD 11 exposure. The observed frequency of defects confirmed that in ICR mice 13-cis-RA is about 10-fold less potent than all-trans-RA as a limb teratogen (Kwasigroch and Kochhar, '80; Kochhar and Penner, '87). Effects observed via image analysis following maintenance of limbs in serum-free culture medium were dose dependent. Low dose treatment produced occasional polydactyly. The intermediate dose caused somewhat variable region-dependent increases in cartilaginous bone anlagen area. The high dose of 13-cis-RA produced irregular limb outlines, a reduction in bone anlagen area, and an inhibition of alcian blue staining of cartilage without affecting morphogenesis of bone anlagen. These results confirm that, when the effects of the administered doses are evaluated, 13-cis-RA is a much less potent teratogen in comparison to the all-trans isomer. More importantly, the results show that retinoids can enhance (at low and intermediate doses), depress (at high doses), or eliminate (high dose) chondrogenenic expression during limb morphogenesis in vitro. This indicates that retinoids such as 13-cis-RA can manipulate events in development in a variety of ways (i.e., produce malformations, interfere with chondrogenic expression without affecting morphogenesis, and stimulate growth) in a dose- and time-dependent manner. Although the ability of RA to act as a true morphogen has recently been questioned (Wanek et al., '91; Noji et al., '91), the results presented here support the position that RA can

Topics: Abnormalities, Drug-Induced; Animals; Body Weight; Cleft Palate; Culture Techniques; Dose-Response Relationship, Drug; Extremities; Female; Fetal Resorption; Fetal Viability; Gestational Age; Isotretinoin; Limb Deformities, Congenital; Maternal-Fetal Exchange; Mice; Mice, Inbred ICR; Pregnancy; Radiography; Tail

The effect of dietary 13-cis-retinoic acid (CRA) on hepatic methionine metabolism was examined in young male rats. Rats were fed a 10% casein diet (controls) or this diet supplemented with L-methionine (10 g/kg diet), with or without the addition of CRA (100 mg/kg diet), for 10 d. Methionine-supplemented rats exhibited 7.3- and 1.7-fold greater concentrations of hepatic S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), respectively, relative to controls, which resulted in a 4.9-fold greater SAM:SAH ratio. Likewise, hepatic methionine and taurine concentrations were 6.9- and 4.3-fold greater, respectively, in methionine-supplemented rats than in controls. The addition of CRA to the methionine-supplemented diet prevented the elevations in the hepatic methionine concentration and the SAM:SAH ratio, whereas taurine levels were greater than in methionine-supplemented rats. In rats pretreated with the methionine-supplemented diet, a reduction in the SAM:SAH ratio occurred within 2 d following the addition of CRA to the methionine-supplemented diet. Rats receiving the methionine-supplemented diet exhibited 9.2- and 3.7-fold greater urinary taurine and inorganic sulfate excretions, respectively, relative to controls. Addition of CRA to the methionine-supplemented diet significantly reduced sulfate excretion by 21%. These findings indicate that dietary CRA has the ability to alter the catabolism of methionine and subsequently influence hepatic transmethylation as reflected by the SAM:SAH ratio.

Topics: Animals; Body Weight; Dose-Response Relationship, Drug; Isotretinoin; Liver; Male; Methionine; Rats; Rats, Inbred Strains; S-Adenosylmethionine; Sulfur

Experimental evidence exists to indicate that retinoids may act as detergents to disrupt biological membranes. Taurine, an amino sulfonic acid, has been shown to possess membrane-stabilizing and cytoprotective properties. This study was undertaken to test whether taurine coadministered with isotretinoin might be able to protect against the teratogenic effects of the retinoid. Our study failed to find any support for this speculation. Whether challenged against a 75 (mildly teratogenic) or 150 (very teratogenic) mg/kg/day dose of isotretinoin, taurine for the most part worsened the retinoid embryotoxicity. While in a few combinations taurine decreased the resorption or malformation rate associated with isotretinoin, the decrease was, at best, marginal. In no case was taurine able to decrease these rates to those noted in the controls.

Topics: Animals; Body Weight; Embryo, Mammalian; Female; Gestational Age; Isotretinoin; Pregnancy; Rats; Rats, Inbred Strains; Taurine; Teratogens

Systemic treatment of adult male New Zealand albino rabbits with 13-cis-retinoic acid (isotretinoin) resulted in a reduction in the size of the meibomian gland. Clinical signs of toxicity included weight loss, alopecia, dry skin and mild conjunctival erythema with crusting on the eyelid margin. Histopathologic findings included thickening of duct and ductule epithelium, decrease in acinar tissue, accentuation of basaloid cells and evidence of periacinar fibrosis. The model presents the first experimental data to indicate that systemic 13-cis-retinoic acid effects meibomian gland structure in a laboratory model. Future functional studies of this model may yield important insights into the relationships between meibomian gland morphology, function, the ocular surface and the pathogenesis of blepharo-conjunctivitis.

Topics: Alopecia; Animals; Blepharitis; Body Weight; Conjunctivitis; Eyelid Diseases; Isotretinoin; Male; Meibomian Glands; Rabbits

A 9-year-old boy, treated with high-dose isotretinoin therapy for fibrodysplasia ossificans progressiva, developed dense metaphyseal bands and growth arrest. Discontinuance of isotretinoin therapy was followed by gradual decrease of metaphyseal bands and resumption of clinical growth. The dense metaphyseal bands may be related to the known action of retinoids as modulators of chondrocyte phenotype and gene expression.

Topics: Adolescent; Body Weight; Bone and Bones; Bone Development; Child; Growth; Humans; Isotretinoin; Male; Myositis Ossificans; Radiography; Torticollis; Tretinoin

Topics: Animals; Benzofurans; Body Weight; Female; Food Contamination; Isotretinoin; Liver; Macaca fascicularis; Polymers; Squalene; Tretinoin

Using etretinate as a model compound, the bone changes characteristic of hypervitaminosis A were evaluated in the rat in terms of tibial bone-breaking strain. Dose-related effects were observed in the dose range of 5-30 mg/kg p.o. for 15 days. The model proved a simple and precise means of assessing hypervitaminosis A in this species. Isotretinoin also showed a small but significant reduction in tibial breaking strain, but with a shallow dose-response curve in the range of 50-150 mg/kg.

Topics: Animals; Body Weight; Bone and Bones; Dose-Response Relationship, Drug; Etretinate; Female; Isotretinoin; Rats; Tensile Strength; Tibial Fractures; Tretinoin; Vitamin A

Weanling rats were fed for 4 weeks semipurified diets containing 0, 100 or 300 mg 13-cis retinoic acid per kg diet. The activities of (Na+ + K+)-ATPase, Mg2+-ATPase and gamma-glutamyltranspeptide were measured in submandibular salivary gland (SMSG) homogenates. The activity of (Na+ + K+)-ATPase in the SMSG was reduced in rats fed 13-cis retinoic acid. There was no effect on the activities of the other two enzymes. Fatty acid composition of total lipids in SMSG suggest that decrease in (Na+ + K+)-ATPase activity may be associated with changes in fatty acid composition of total lipids.

Topics: Adenosine Triphosphatases; Animals; Body Weight; Ca(2+) Mg(2+)-ATPase; Cell Membrane; Fatty Acids; gamma-Glutamyltransferase; Isotretinoin; Male; Organ Size; Rats; Rats, Inbred Strains; Sodium-Potassium-Exchanging ATPase; Submandibular Gland; Tretinoin

Syrian hamsters were treated with either a low (10 mg/kg body weight) or high (40 mg/kg body weight) single dose of bis(2-oxopropyl)nitrosamine (BOP) and beginning 1 week later fed either low (0.2 mmol/kg diet) or high (0.4-1.0 mmol/kg diet) levels of one of four retinoids [13 cis retinoic acid (13-cis-RA), N-ethylretinamide (ERA), N-(2-hydroxyethyl)retinamide (OHERA) or N-(phenyl)retinamide (PRA)] for periods of 40 or 50 weeks. The high retinoid levels (0.4-1.0 mmol/kg diet) fed following the highest BOP treatment enhanced pancreatic carcinoma yields (average number/effective animal) in males fed all four retinoids, and in females fed ERA and 13-cis-RA. Enhanced adenoma yields were also seen in all groups when high retinoid levels were fed following 40 mg BOP/kg body weight. However, these retinoid levels caused an increased adenoma yield in male hamsters only and did not modify carcinoma yields when fed following 10 mg BOP/kg body weight. Similarly, tumor yields at extra-pancreatic sites were elevated in retinoid-fed hamsters of both sexes after 40 mg BOP/kg body weight and in males fed ERA and 13-cis-RA after 10 mg BOP/kg body weight when retinoids were given at the high levels (0.4-1.0 mmol/kg diet). Increased incidences of bile duct and liver tumors in particular were found in hamsters given 40 mg BOP/kg body weight. Consumption of retinoid levels of 0.4 mmol/kg diet and above was also associated with a high incidence of liver cell necrosis, ovarian cysts and ovarian hemorrhage. Retinoids (ERA, OHERA, and PRA) fed at the low level (0.2 mmol/kg diet) following the low BOP dose did not enhance carcinogenesis in the pancreas or at other sites and did not cause alterations in morphologic observations.

Topics: Animals; Body Weight; Cricetinae; Dose-Response Relationship, Drug; Female; Isomerism; Isotretinoin; Male; Mesocricetus; Neoplasms; Nitrosamines; Pancreatic Neoplasms; Sex Factors; Tretinoin

Groups of Charles River Sprague-Dawley male rats were given intragastric intubations of methylbenzylnitrosamine after receiving one of the following diets for 4 weeks: control, zinc-deficient, or zinc-deficient diet plus 4% ethanol in the drinking water. One zinc-deficient group was zinc repleted after the dosing period; the other group, zinc-deficient plus 4% ethanol, received 13-cis-retinoic acid (13-cis-RA) after the dosing period. Zinc deficiency significantly enhanced esophageal tumor incidence; the addition of ethanol further enhanced tumor incidence. Zinc repletion reduced tumor incidence, whereas the addition of 13-cis-RA enhanced tumor incidence.

Topics: Animals; Body Weight; Cocarcinogenesis; Copper; Diet; Dimethylnitrosamine; Esophageal Neoplasms; Ethanol; Isotretinoin; Male; Neoplasms, Experimental; Rats; Rats, Inbred Strains; Tretinoin; Zinc