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Various substances of steroidal or nonsteroidal structure may serve as an alternative for the antiandrogenic treatment of acne. Compounds with antiandrogenic properties like cimetidine or ketoconazole are rarely administered for acne due to their weak effects. In contrast, spironolactone is an effective antiandrogen that shows good treatment effects in hirsutism and acne. Side effects occur frequently and are dose dependent. Isotretinoin--the most effective agent in acne therapy--has been under discussion for additional antiandrogenic properties for years. At present there is additional evidence for the antiandrogenic effects of isotretinoin. Regarding substances acting on both levels, androgen receptor binding and 5 alpha-reductase inhibition, the question is raised whether the term 'antiandrogen' should be amplified by including the 5 alpha-reductase inhibitors. This would pay tribute to the biological aspect of antiandrogenicity that takes into account not only the mode of action but also the effects of the substance. Under this aspect type 1 5 alpha-reductase inhibitors may gain attention in the future.
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The present paper assesses the chemopreventive potential of retinoic acid on benzoyl peroxide (BPO)-induced cutaneous tumor promotion response and oxidative stress in murine skin. In this study, we have shown the activities of cutaneous antioxidant enzymes and phase II metabolizing enzymes and the glutathione content were decreased while epidermal ornithine decarboxylase (ODC) activity and DNA synthesis were induced in benzoyl peroxide treated animals. Topical application of retinoic acid resulted in significant inhibition of benzoyl peroxide-induced epidermal ornithine decarboxylase activity and DNA synthesis. Application of retinoic acid at three different doses prior to the application of benzoyl peroxide recovered the depleted level of glutathione, inhibited activities of antioxidant and phase II metabolizing enzymes, thus resulting in significant inhibition of oxidative stress in dose dependent manner. Enhanced susceptibility of cutaneous microsomal lipid peroxidation and xanthine oxidase activity were significantly reduced (P > 0.05). The antimutagenic effect of retinoic acid was tested against benzoyl peroxide mediated mutagenicity in Salmonella typhimurium strain TA-98 and TA-100 using 3-methyl cholanthrene-induced murine skin (S9 fraction) as the metabolic activation system. Indeed, with the addition of various concentrations of retinoic acid there was significant reduction in the number of revertants per plate in concentration dependent manner. In summary, our data indicates that retinoic acid may exhibit cancer chemopreventive activity in skin tumorigenesis model.
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Three of 50 patients treated with isotretinoin (1 mg/kg/day) for cystic acne complained of poor night vision and/or excessive glare sensitivity. While still receiving the drug or shortly thereafter, two patients were found to have abnormal dark-adaptation curves, with elevations of either cone or rod thresholds, or both. Two patients had abnormal electroretinograms (ERGs). One had a mildly abnormal electro-oculogram. The dark-adaptation curves were normal for one patient several months after isotretinoin therapy was discontinued. Two patients had elevated cone thresholds at least one year later. Six months following cessation of therapy, the ERG was still abnormal for one patient, but continued improvement was evident at 25 months; for the second patient, the ERG was normal at one year. Analysis of Naka-Rushton parameters for the ERG scotopic b-wave stimulus-response curves indicated response compression for two patients, as evidenced by a reduction in the maximum response. For one patient, the half-saturation constant was elevated 0.7 log units, suggesting reduction of retinal sensitivity, perhaps from decrease in retinal photopigment concentration. We suspect that isotretinoin may complete for normal retinol binding sites on cell surfaces or transport molecules. A prospective study is currently underway to determine if a clinically measurable adverse effect on retinal function is seen with greater frequency.
The combination of isotretinoin with PUVAsol is more effective compared with PUVAsol alone for treating chronic plaque psoriasis.
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The Canadian Saskatchewan Health Database and the United Kingdom General Practice Research Database.
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Fifty-one assessable patients, 2 to 12 years of age, were treated with oral cis-RA administered in two equally divided doses daily for 2 weeks, followed by a 2-week rest period, for up to 12 courses. The dose was escalated from 100 to 200 mg/m2/d until dose-limiting toxicity (DLT) was observed. A single intrapatient dose escalation was permitted.
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Vitamin A is essential for growth and development, reproduction and vision in humans. Chemical modification of vitamin A has yielded compounds showing therapeutic promise in skin and neoplastic diseases. The medicinal use of retinoids (vitamin A and its derivatives) is limited by the toxicity associated with this group of compounds. One retinoid, 13-cis-retinoic acid, has proved to be quite effective in the treatment of severe recalcitrant cystic acne under conditions in which toxicity is manageable.
No significant differences were found in lumbar spine and femoral BMD between the patient and control groups at the beginning of the study (P > 0.05), and no statistically significant difference was observed between the BMD values in patients at the beginning vs. the end of treatment (P > 0.05). No statistically significant difference in bone turnover markers was found between patients and controls at the beginning of the study (P > 0.05), and no statistically significant changes in bone turnover markers were observed in patients at the beginning vs. the end of treatment (P > 0.05).
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Eighty-five patients with newly diagnosed JMML were enrolled on AAML0122 between 2001 and 2006. Forty-seven consented to receive tipifarnib in a phase II window before proceeding to a phase III trial of CRA in combination with fludarabine and cytarabine followed by HSCT and maintenance CRA. Thirty-eight patients enrolled only in the phase III trial.
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The perceptions of patients regarding the benefits, disadvantages, and importance of their participation in a long-term cancer chemoprevention trial, the Isotretinoin-Basal Cell Carcinoma Prevention Trial, were assessed through a questionnaire mailed at the conclusion of the 3-year treatment period of the trial. Responses were evaluated overall, as well as within subgroups defined by sex, age, education level, treatment group, presence of side effects, and the number of skin biopsies performed during the 3-year intervention phase. Overall, "careful medical follow-up received" (43%) and "being part of a research effort" (24%) were the most frequently cited important benefits, while the "amount of time taken to attend clinic" (32%) and "side effects" (20%) were the most frequently cited unpleasant aspects of trial participation. Most surveyed patients viewed the study as "very or extremely important" to their general health (62%) and their skin cancer condition (88%) and, as a result of participation, felt "much or somewhat better" physically (52%). The majority indicated that they would "definitely or probably" be willing to take part in another research study (79%) and take the study medication, if it were shown to be effective in the trial (78%). Overall and subgroup data provide important insights into patient motivations and attitudes regarding cancer chemoprevention trial participation, adherence, and satisfaction.
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Minimum inhibitory concentration of Zolav(®) (a p-carboethoxy-tristyrylbenzene derivative) against Propionibacterium acnes was determined by following a standard protocol using Mueller-Hinton broth and serial dilutions in a 96-well plate. Cytotoxicity effects on human umbilical vein endothelial cells and lung cells in the presence of Zolav(®) (a p-carboethoxy-tristyrylbenzene derivative) were investigated by determining the growth inhibition (GI50) concentration, total growth inhibition concentration, and the lethal concentration of 50% (LC50). The tryptophan auxotrophic mutant of Escherichia coli strain, WP2 uvrA (ATCC 49979), was used for the AMES assay with the addition of Zolav(®) (a p-carboethoxy-tristyrylbenzene derivative) tested for its ability to reverse the mutation and induce bacterial growth. The in vivo effectiveness of Zolav(®) (a p-carboethoxy-tristyrylbenzene derivative) was tested in a P. acnes mouse intradermal model where the skin at the infection site was removed, homogenized, and subjected to colony-forming unit (CFU) counts.
Retinoids and interferon alpha have shown synergistic activity against metastatic renal cell carcinoma in previous preclinical and clinical studies. Based on these results, we conducted a phase II trial of 13-cis-retinoic acid (cRA) at 1 mg/kg/dose interferon alpha2a (IFN) at initial dose of 9 MU three times a week. Thirty-one patients were entered, all evaluable for toxicity and 30 evaluable for response. One patient achieved a partial response and 10 patients achieved stable disease. Toxicity was mild and primarily related to interferon. No toxic deaths were reported. Median survival time was 10 months. At the dose and schedule used, cRA and interferon-alpha2a showed low activity against metastatic renal cell carcinoma. Further studies with this combination are not recommended.
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The study demonstrates that measuring of the plasma levels may be a helpful tool to monitor the individual therapeutic dose regimen in patients with severe acne in order to minimize undesired side effects and to control oral intake.
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Accumulating evidence suggests that synthetic retinoids may be capable of affecting the differentiation and growth of nervous tissue in vivo and in vitro. On the other hand, adverse reactions concomitant with brainstem involvement definitely or probably related to oral retinoid therapy have been reported in a small number of patients.
There is a paradoxical increase in fasting serum adiponectin concentration during the 13-cis-retinoic acid-induced reduction in insulin sensitivity.
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We observed a clinical response in all patients, with 8 complete remissions (CR) and 14 partial remissions (PR). When CR was obtained, the treatment was progressively decreased (average of 3.5 capsules/day); 4/22 patients experienced side-effects, mainly gastro-intestinal.
A 27-year-old white woman developed severe thrombocytopenia and elevated transaminases after 3(1/2) months of treatment with isotretinoin. Prior to the onset of thrombocytopenia, the patient had also received a 10-day course of cephalexin. Rectal bleeding was reported by the patient, who was otherwise asymptomatic. Liver enzyme values returned to normal approximately 1 week after discontinuation of isotretinoin; however, platelet counts required approximately 2 months to normalize. Based on the Naranjo probability scale, possible causality exists between isotretinoin and thrombocytopenia.
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The dynamics of the increase in CD69 early activation antigen expression on CD56+ NK cells is systematic and serial with the increase being significantly higher on day six of the first cycle in group B patients with clinical response, compared to those without, indicating possible predictive value of CD69 expression for clinical response to chemoimmunotherapy.
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The cell differentiation potential of 13-cis retinoic acid (RA) has not succeeded in the clinical treatment of glioblastoma (GBM) so far. However, RA may also induce the expression of resistance genes such as HOXB7 which can be suppressed by Thalidomide (THAL). Therefore, we tested if combined treatment with RA+THAL may inhibit growth of glioblastoma in vivo. Treatment with RA+THAL but not RA or THAL alone significantly inhibited tumour growth. The synergistic effect of RA and THAL was corroborated by the effect on proliferation of glioblastoma cell lines in vitro. HOXB7 was not upregulated but microarray analysis validated by real-time PCR identified four potential resistance genes (IL-8, HILDPA, IGFBPA, and ANGPTL4) whose upregulation by RA was suppressed by THAL. Furthermore, genes coding for small nucleolar RNAs (snoRNA) were identified as a target for RA for the first time, and their upregulation was maintained after combined treatment. Pathway analysis showed upregulation of the Ribosome pathway and downregulation of pathways associated with proliferation and inflammation. In conclusion, combined treatment with RA + THAL delayed growth of GBM xenografts and suppressed putative resistance genes associated with hypoxia and angiogenesis. This encourages further pre-clinical and clinical studies of this drug combination in GBM.
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A randomized phase III trial was conducted to determine whether combination therapy with 13-cis-retinoic acid (13-CRA) plus interferon alfa-2a (IFNalpha2a) is superior to IFNalpha2a alone in patients with advanced renal cell carcinoma (RCC).
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Of the 82 female patients who were enrolled in the first study, 79 patients were included in this study. Twelve months after the end of systemic isotretinoin treatment, patients were reevaluated by using the same parameters which include anti-Mullerian hormone (AMH), ovarian volume (OV), antral follicle count (AFC), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, free testosterone and total testosterone.
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Contraception provides significant benefits for women's and children's health, yet an estimated 225 million women had an unmet need for modern contraceptive methods in 2014. Interventions delivered by mobile phone have been demonstrated to be effective in other health areas, but their effects on use of contraception have not been established.
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(1) Isotretinoin, a vitamin A derivative, is marketed as an oral treatment for refractory severe acne. It is known to carry a risk of severe birth defects. The skin tends to become dry and fragile during isotretinoin treatment; (2) Some adverse effects of isotretinoin are caused by damage to the intestinal mucosae. These effects include bloody and mucousy diarrhoea, colitis, ileitis (sometimes severe and necessitating surgery), and aggravation of inflammatory bowel disease such as Crohn's disease; (3) Isotretinoin can affect all mucous membranes, causing multiple disorders of varying severity, affecting: the eyes (conjunctivitis); ear, nose and throat (epistaxis); respiratory tract; gastrointestinal tract (colitis); and urinary tract; (4) Patients must be informed of the risk of mucosal damage and especially of intestinal disorders associated with isotretinoin therapy. Isotretinoin should be borne in mind as a possible cause when a young patient presents with gastrointestinal disorders, and its withdrawal should be envisaged. Isotretinoin is an additional risk factor in patients with a personal or familial history of inflammatory bowel disease.
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Acne is a prominent skin condition affecting >80% of teenagers and young adults and ~650 million people globally. Isotretinoin, a vitamin A derivative, is currently the standard of care for treatment. However, it has a well-established teratogenic activity, a reason for the development of novel and low-risk treatment options for acne.
We relate the case of a drug addict of 31 years old whose dependence to the amineptine got complicated with severe acne-like lesions, as it sometimes happens. Compared, with teenage acne, severe acne can be distinguished by its late out break, its monstrous nature and its larger surface area. Amineptine has been found (or its metabolites) in the plasma, the urine. The treatment consists in the stopping of the drug addiction, combined with the prescription of isotretinoin.
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Nelson et al. confirmed the previously described antiproliferative effect of isotretinoin on human sebocytes. They attributed a portion of this decrease to cell cycle arrest and detected sebocyte apoptosis, which was not recapitulated by alitretinoin or tretinoin. These events were specific to sebocytes, as isotretinoin failed to induce apoptosis in keratinocytes. Isotretinoin-induced apoptosis was shown to be an RAR-independent mechanism.
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Visual observations revealed that there was no significant change (p < 0.05) w.r.t. erythema, skin sagging and wrinkles in the skin of the animals treated with NLCs formulation compared to the marketed product(s). The malondialdehyde levels were found to be significantly reduced, whereas glutathione levels were increased with the application of NLCs vis-à-vis control and test formulations. The NLCs were able to maintain the normal redox-balance of UV-irradiated skin, and were better tolerated by the animals.
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Assuming a relapse rate of 21.45%, it was found that isotretinoin therapy compares favourably with the other regimens. After 50 and 35 months, systemic isotretinoin cumulative costs were less than those incurred in oral antibiotic and oral antibiotic/anti-androgen therapy, respectively. For the stepped therapy of oral antibiotics followed by systemic isotretinoin, these break-even periods were 56 and 39 months, respectively. The cost per successfully treated patient receiving isotretinoin was R8941. This compares well with the cost for those patients receiving chronic oral antibiotics, which after 5 years amounted to R10 428 per patient. Sensitivity analyses proved these findings to be robust to variations in the isotretinoin relapse rate, and the cost of oral antibiotic therapy and the concomitant use of topical therapies.
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We have previously reported that obesity-induced diabetes developed in high-fat diet (HFD)-fed BDF1 mice. This is caused by insufficient insulin response to an excess glucose load. In this study, we have shown that the enhanced expression of retinaldehyde dehydrogenase 3 (Raldh3) causes functional disorders of pancreatic islets in diabetic mouse models. In the pancreatic islets of HFD-induced diabetic BDF1 mice and spontaneously diabetic C57BL/KsJ(db/db) mice, gene expression analysis with oligonucleotide microarray revealed a significant increase in Raldh3 expression. Exposure to a culture medium containing a higher glucose concentration (25 mM) significantly increased Raldh3 expression in murine MIN6 and alphaTC1 clone 9 cells, which derived from the α and β-cells of pancreatic islets, respectively. Overexpression of Raldh3 reduced the insulin secretion in MIN6 cells, and surprisingly, increased the glucagon secretion in alphaTC1 clone 9 cells. Furthermore, the knockdown of Raldh3 expression with siRNA decreased the glucagon secretion in alphaTC1 clone 9 cells. Raldh3 catalyzes the conversion of 13-cis retinal to 13-cis retinoic acid and we revealed that 13-cis retinoic acid significantly reduces cell viability in MIN6 and alphaTC1 clone 9 cells, but not in cells of H4IIEC3, 3T3-L1, and COS-1 cell lines. These findings suggest that an increasing expression of Raldh3 deregulates the balanced mechanisms of insulin and glucagon secretion in the pancreatic islets and may induce β-cell dysfunction leading to the development of type 2 diabetes.
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Is there a relationship between severe teenage acne and endometriosis?
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Aging of the skin is a complex biological process which is influenced by the interaction of several intrinsic and extrinsic factors. Intrinsic or chronological aging is an inevitable, genetically programmed process, of unclear underlying mechanism, for which no prevention or effective treatment is currently available. Photoaging refers to the gross and microscopic cutaneous changes that are induced by cumulative exposure to UV radiation and are superimposed on the background of chronological aging. Although primarily an aesthetic problem with significant psychological effects, photoaging constitutes the background for the development of precancerous and cancerous skin lesions.Overwhelming clinical and histological evidence indicate that certain structural changes induced by excessive sun exposure can be reversed, to some extent, by the use of topical retinoids. A number of retinoid compounds, for example tretinoin, isotretinoin, retinaldehyde and tazarotene, have been employed for the treatment of photoaged skin, and demonstrate beneficial clinical and histological effects. Adverse effects have been limited to an irritant reaction of variable intensity presenting with dryness, scaling and erythema. Ongoing research will enhance our understanding of the molecular mechanisms that determine the effects of retinoids on photodamaged skin and contribute to the employment of new, more effective and less irritating retinoid compounds.
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To determine relative cost-effectiveness of common therapeutic regimens using published data.
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A combination of low-dose isotretinoin and oral azithromycin pulse is effective in severe acne and has a reasonably acceptable adverse-effect profile and low post-treatment relapse rates.
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In adult organ transplant recipients, nodulocystic acne induced by the use of cyclosporine can be treated successfully with isotretinoin. Cyclosporine's acnegenic effects in children and the pediatric response to treatment are less clear.
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The purpose of this study was to review the data on the etiology, risk factors, clinical presentations, and diagnosis of acute sacroiliitis. A Pubmed search utilizing the indexing term "acute sacroiliitis" was conducted and the data pertinent to the aim of the review was extracted and organized in accordance with the preplanned structure of the manuscript. The diagnosis of acute sacroiliitis is often challenging because of both the relative rarity of this presentation and diverse character of acute sacroiliac pain, frequently mimicking other, more prevalent disorders. Technetium bone scintigraphy can localize the disease process to the sacroiliac joint, while computed tomography or magnetic resonance imaging can be used for the detailed characterization and the extent of the disease as well as the diagnosis of complications. Pyogenic sacroiliitis is by far the most common cause of acute sacroiliitis. Brucellosis, acute sacroiliitis in the course of reactive arthritis, and crystalline-induced sacroiliitis frequently imitate pyogenic sacroiliitis. Acute sacroiliitis can rarely be also related to hematological malignancies or treatment with isotretinoin. Awareness to the possibility of acute sacroiliitis and a thorough physical examination are the necessary prerequisites to its timely diagnosis, while the appropriate laboratory and imaging studies should confirm the precise diagnosis and direct the appropriate treatment strategy.