Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of all-trans-retinoic acid were investigated on the immune responses in C57Bl/6 mice after daily oral administration for one week. In selected experiments the immunosuppressive chemicals, cyclophosphamide and cyclosporin A were used in conjunction with retinoic acid. Retinoic acid stimulated the production of antibodies against sheep red blood cells and DNP-Ficoll; however, retinoic acid did not reverse the depression caused by immunosuppressive chemicals. In non-immunized animals retinoic acid stimulated the production of IL-1 but not of IL-2. The mitogenic responses of splenocytes against concanavalin A, phytohemagglutinin and pokeweed mitogen were depressed after the retinoic acid treatment; those against lipopolysaccharide were not influenced. Treatment with retinoic acid did not alter the mixed leukocyte responses but increased the activity of NK cells. Results indicate that retinoic acid may act as an adjuvant via activating macrophages, however, retinoic acid cannot reverse the immunosuppression induced by potent chemicals.
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PMID:Adjuvant activity of all-trans-retinoic acid in C57Bl/6 mice. 162 15

In an attempt to elucidate the mechanisms underlying retinoid-induced hyperlipidemia, the effects of etretinate (Tigason) and isotretinoin (Roaccutane) on two different plasma fat elimination variables and on the plasma fatty acid composition were studied. Twelve patients with various hyperkeratotic disorders participated in a double-blind cross-over study of etretinate and isotretinoin. Each drug was given for 8 weeks with an 8-week intermission. On five occasions an intravenous fat tolerance test (IVFTT) was performed and the lipoprotein lipase activity (LPLA) in adipose tissue and skeletal muscle was measured. Isotretinoin significantly reduced the fat elimination rate as measured by IVFTT (p less than 0.001) and also decreased the muscle LPLA (p less than 0.05). The etretinate-induced depression of these variables was not statistically significant. The LPLA of adipose tissue and the plasma fatty acid composition were not markedly altered by any of the drugs. The observed changes are probably not sufficient to entirely explain retinoid-induced hyperlipidemia but the results strengthen the opinion that plasma lipid metabolism is more unfavourably affected by isotretinoin than etretinate.
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PMID:Plasma fat elimination tissue lipoprotein lipase activity and plasma fatty acid composition during sequential treatment with etretinate and isotretinoin. 243 78

Retinoic acid, an endogenous metabolite of vitamin A (retinol), possesses striking biological activity akin to a morphogen in developing and regenerating vertebrate limbs. Systemic administration of retinoic acid (RA) to pregnant mammals during the period of limb organogenesis invariably results in dose-dependent dysmorphogenesis. In an attempt to uncover the mode of action of RA in the developing limb bud we analyzed, by HPLC methods, the levels of RA and its metabolic precursor, retinol, in embryonic mouse tissues prior to and following maternal exposure to a teratogenic dose of RA. Detectable levels of both RA and its isomer 13-cis-retinoic acid were found in the limb buds of Day 11 mouse embryos (40 +/- 2 somites). Although retinol was the major retinoid found in ethanolic extracts of either whole embryo or the limb buds, the latter is enriched in RA compared to the whole embryo. This indicated either a higher degree of retinol metabolism or a sequestration of RA in the limb bud compared to the rest of the embryo at this stage of development. A study of the time course of retinoid levels in treated embryos showed that changes occur rapidly, are stable for several hours, and then begin to return to pretreatment levels. After a maternal dose of 10 mg/kg RA, which resulted in a mild degree of limb anomalies, peak RA levels in the limb bud increased 50-fold over the endogenous level; a full 300-fold increase was found after a 100 mg/kg dose which results in 100% incidence of phocomelia. Interestingly, a dose-dependent depression in retinol levels was observed after RA treatment both in maternal plasma as well as the embryo. Studies are in progress to trace the intracellular disposition of both retinol and RA as well as any further active metabolite of RA in the limb buds and other embryonic tissues.
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PMID:Elevations in the endogenous levels of the putative morphogen retinoic acid in embryonic mouse limb-buds associated with limb dysmorphogenesis. 273 39

A renal transplant recipient who developed severe acne 6 months after transplantation is described. Maintenance immunosuppression consisted of cyclosporine A (CsA), azathioprine and prednisone. Tapering the prednisone dose to as low as 5 mg/day, in addition to topical tetracycline, Retin-A cream, and systemic antimicrobial therapy failed to control the progression of the skin lesions. Despite therapy with isotretinoin (Accutane), the lesions continued to progress with nodulocystic transformation (acne conglobata) and isotretinoin was discontinued after 4 months. However, the condition continued to worsen with the development of a systemic illness with daily fever, diaphoresis, and depression. High fever (103 degrees F) with shaking chills prompted hospitalization. Withdrawal of CsA resulted in rapid and continuous improvement of the skin lesions. After 12 months of follow-up, the lesions significantly resolved except for residual areas of scarring. No episodes of acute allograft rejection occurred. In conclusion, we suggest that CsA therapy may be associated with the development of acne. Nodulocystic transformation (acne conglobata) may occur despite the use of isotretinoin. Finally, withdrawal of CsA may lead to resolution of the skin disease and should, therefore, be considered as a therapeutic option for severe and treatment-resistant cases.
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PMID:Acne: a potential side effect of cyclosporine A therapy. 873 Apr 42

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) concentrations. We have demonstrated that micromolar concentrations of HPR, retinoic acid, 13-cis-retinoic acid or Acitretin significantly reduced the in vitro hydrolysis of retinyl palmitate. In contrast, Temarotene stimulated retinyl palmitate hydrolysis by BSI-REH. Retinoic acid and 13-cis-retinoic acid produced transient, but significant, depressions of both serum retinol and RBP concentrations, when the individual retinoids were administered orally to rats. The duration of the depression was shorter than we previously observed with acute HPR administration. Furthermore, Acitretin appeared to function with bimodal activity, producing significant depression of serum retinol at 2 h and 24 h. No effect of Acitretin or Temarotene on serum RBP concentration was observed. The alterations observed in BSI-REH activity, serum retinol and RBP concentrations provide evidence that these retinoids can alter liver retinyl ester hydrolysis, but the effects observed on serum retinol concentration can only be partially explained by the BSI-REH activity.
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PMID:Multiple retinoids alter liver bile salt-independent retinyl ester-hydrolase activity, serum vitamin A and serum retinol-binding protein of rats. 898 Jun 37

Isotretinoin (Accutane, Roche Laboratories Inc, Nutley, NJ) is an important drug, not only for the treatment of severe acne, but also for other diagnoses and in chemoprevention settings. Because the use of isotretinoin is increasing, it is important for physicians to be aware of the adverse events, toxicities, and management issues related to its use. The most important issue is that of congenital defects, which has resulted in new pregnancy prevention policies and programs implemented by the manufacturer. A relatively new concern is that of depression associated with isotretinoin use, also resulting in new policies placed by the manufacturer and the FDA. The most common adverse effects observed during treatment are mucocutaneous and ocular in nature, but laboratory abnormalities and effects in the nervous, musculoskeletal, gastrointestinal, pulmonary, hematologic, and other systems are also described. Additionally, potential drug interactions, follow-up, and toxicity prevention measures are discussed.
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PMID:Safety issues in isotretinoin therapy. 1159 72

The association between isotretinoin therapy and depressive symptoms in acne patients has generated much recent interest but has not been systematically explored. A 17-year-old man with acne vulgaris developed symptoms of acute depression two weeks after beginning isotretinoin therapy. The depressive symptoms improved with reduction of isotretnoin dose and treatment with sertraline. Of note, however, is that when the isotretinoin dose was again increased, the depressive symptoms recurred despite clearing of the skin, leading to an unsuccessful suicide attempt. Isotretinoin was finally discontinued and the depression rapidly resolved. Although the effects of hypervitaminosis A may be involved aetiologically, the predictive factors of drug-related depression remain unclear. Significant depressive symptoms that develop during the course of treatment need close monitoring and may necessitate both antidepressant therapy and discontinuation of the drug. Given the uncertain causal relationship between isotretinoin and depression, versus the potential psychological benefits of effective acne treatment, systematic studies exploring the impact of isotretinoin on mood are needed.
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PMID:Acne, isotretinoin treatment and acute depression. 1258

Isotretinoin (Accutane; Hoffmann-La Roche, Nutley, NJ) is a drug closely related to the chemical structure of vitamin A. The pharmacology and toxicology of these two retinoids are similar enough to warrant comparison. Accutane is a powerful drug that its manufacturer, Roche, indicates is limited for severe recalcitrant nodular acne. This potency is also reflected in Accutane's well-known ability to produce severe birth defects if taken during pregnancy. Less well known is the risk of this lipid-soluble chemical to affect the central nervous system. Reports of intracranial hypertension, depression, and suicidal ideation with Accutane use have prompted an examination of its serious and life-threatening potential. Although Roche has added a warning to its product label for signs of depression, and suicidal ideation, this product is overprescribed for all forms of acne, including mild and moderate cases that have not been treated with alternative medications with less risk of depression and suicide. There is no contesting that this drug is effective at clearing up the most severe forms of acne, but the public must be informed of the proper limited indication for its use, because depression and suicide can follow in patients with no prior history of psychiatric symptoms or suicide attempts.
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PMID:Overview of existing research and information linking isotretinoin (accutane), depression, psychosis, and suicide. 1262 95

Isotretinoin is a retinoid that is approved for the treatment of cystic acne. There has been a growing interest in the possible relationship between isotretinoin use and increased risk of depression and suicide. The issue, however, remains controversial. This review examines the available evidence on this association, including published case reports, studies of challenge-rechallenge, reports to government agencies of isotretinoin-related adverse events involving suicide and depression, and possible biological mechanisms of action. Given the evidence to date, clinicians are advised to counsel their patients about the risk of depression and suicide as possible side effects of isotretinoin use, and to administer self-report questionnaires during treatment to screen for the development of depression. Further epidemiological and neurobiological studies are needed to assess the possible relationship between isotretinoin administration and depression and suicide.
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PMID:Does isotretinoin cause depression and suicide? 1456 49

Isotretinoin is a very effective medication for the treatment of severe recalcitrant acne. However, its use is associated with many side effects, some of which can be very serious. The most important issue is its teratogenicity, which has resulted in new pregnancy prevention policies and programmes implemented by the manufacturer. Recently, the association of isotretinoin with depression has been recognised and new guidelines have been adopted for this possible side effect. The most common adverse events, observed during treatment, are mucocutaneous and ophthalmological. In addition, laboratory abnormalities and effects in the nervous, musculoskeletal, gastrointestinal, pulmonary and other systems have been described.
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PMID:Safety and side effects of the acne drug, oral isotretinoin. 1500 18


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