Isotretinoina: Possível Interferência na Cicatrização Pós-Exodontia / Isotretinoin: Possible Interference in Postextraction Healing

A farmacovigilância é definida como "a ciência e atividades relativas à identificação, avaliação, compreensão e prevenção de efeitos adversos ou quaisquer problemas relacionados ao uso de medicamentos". Os medicamentos têm tanto o potencial de trazer benefícios quanto o de causar danos. O ácido 13-cis-Retinoico ou isotretinoina é um retinoide antiacne de referência no tratamento de doenças dermatológicas não responsivas a terapias convencionais, como a acne cística severa. Os efeitos adversos descritos na bula do medicamento implicam alterações em vários sistemas do corpo humano. Aqueles relacionados ao tecido ósseo, como a calcificação dos ligamentos e tendões, a redução na densidade óssea, o fechamento epifisário e hipercalcemia, possuem maior relevância na odontologia, levantando a hipótese para possível interferência na cicatrização dos alvéolos, após exodontia. Este artigo teve por objetivo realizar uma revisão de literatura reunindo informações sobre a possibilidade de interferência da isotretinoina em cirurgias maxilofaciais. Apesar da escassez de dados científicos conclusivos sobre a interferência da isotretinoína na cicatrização alveolar em humanos, estudos recentes sobre as vias de sinalização dos retinoides abrem novas perspectivas de pesquisa na influência dos retinoides no tecido ósseo alveolar. Esta possibilidade reforça a importância de uma atualização sobre os efeitos adversos da isotretinoína, bem como da anamnese criteriosa em pacientes com histórico de acne severa a fim de evitar complicações.

Pharmacovigilance is defined as "the science and activities related to identification, evaluation, understanding and prevention of adverse effects or problems related to the use of drugs". All drugs have both the potential to cause harm and benefit. 13-cis-Retinoic acid or isotretinoin is a reference anti-acne retinoid in the dermatological diseases treatment not responsive to conventional therapies, such as severe cystic acne. The drug-related side effects described in the medicine package insert imply changes in various human body systems. Those related to bone tissue, such as ligaments and tendons calcification, bone density reduction, epiphyseal closure and hypercalcemia, have great relevance for dentistry, raising the hypothesis of a possible interference in alveoli wound healing after extraction. This article aimed to conduct a literature review in gathering information about the possibility of isotretinoin interference in maxillofacial surgeries. In despite of the scarcity of conclusive scientific data about the influence of isotretinoin on human alveolar wound healing, recent studies on retinoid signaling pathways open new research perspectives for the isotretinoin interference on alveolar bone tissue. This possibility reinforces the importance of an isotretinoin drug-related side effects update, as well as a patients' careful anamnesis with historical severe acne, in order to avoid complications

Study on 13-cis retinoic acid inducing differentiation of three types of human neuroblastoma cell lines in vitro / 中华实用儿科临床杂志

Objective To investigate the effects of 13-cis retinoic acid (13-cis RA) in inducing differentiation of 3 types of human neuroblastoma (NB) cells in vitro.Methods The status of MYCN gene amplification of cultured SH-SY5Y,SK-N-SH and SK-N-BE2 cells was detected by fluorescence in situ hybridization.After treatment with different concentrations of 13-cis RA,morphological changes were observed by phase-contrast microscope,and neuron-specific enolase (NSE) concentrations were determined by enzyme linked immunosorbent assay.The cell viability was measured through cell counting kit-8 assay,and the cell apoptosis was assayed with flow cytometry (FCM).Results The morphological changes in differentiation were observed in all 3 types of NB cells after 13-cis RA treatment.MYCN amplification was detected in SK-N-BE2 cells even after 13-cis RA treatment,while the other 2 cell lines were amplification-null.After different concentrations of 13-cis RA treatment,NSE concentration increased with prolonged time,especially for SK-N-BE2 cell(F =27.00,P ＜ 0.000 1).13-cis RA stimulated cell proliferation within 48 hours of treatment,and then inhibited cell growth.FCM indicated that the degree of apoptosis in SH-SY5Y cell was significantly higher after 13-cis RA treatment of 10 μmol/L concentration for continuous 96 h and 120 h as compared to the control group (F =16.21,P =0.011;F =16.04,P =0.016).Cell apoptosis of SK-N-SH cell after 13-cis RA treatment of 1 μ mol/L and 10 μ mol/L concentration for 48 h,were significantly higher than those of the control group (F =15.05,P =0.012;F =31.18,P =0.005);while SK-N-BE2 cell with different concentrations of 13-cis RA(1 μmol/L,5 μmol/L,10 μ mol/L) for 120 h were significantly higher than those of the control group(F =9.05,P =0.030;F =11.38,P =0.028;F =7.88,P =0.041).Conclusions The present study showed that 13-cis RA could induce differentiation of human NB ceils in vitro.It induces cell proliferation within 48 hours of 13-cis RA,and thereafter suppresses cell growth.No improvement was found in MYCN amplification cells with the detection of DNA level after 13-cis RA treatment,which suggests that combined treatment is possibly needed.

Comparison of the Effects of 13-cis Retinoic Acid and Melatonin on the Viabilities of SH-SY5Y Neuroblastoma Cell Line

OBJECTIVE: Neuroblastoma is one of common childhood tumors. Although its mortality is very high, there is no effective treatment yet. The aim of this project is to evaluate cytotoxic effects of melatonin (MLT) an endogen hormone and 13-cis retinoic acid (13-cis-RA) also named as isotretinoin an analogue of vitamin A on neuroblastoma SH-SY5Y cell line. METHODS: In this study, SH-SY5Y cell line was used. After cell culture, the cells were exposed to different doses of MLT and 13-cis-RA. 24 and 48 hours later. While the viabilities was estimated with MTT cell viability assay test, apoptotic indexes were calculated after staining with TUNEL based apoptosis kit. RESULTS: It was observed that MLT has very effective cytotoxic potential than 13-cis-RA on neuroblastoma cell line. At the same time, when MLT and 13-cis-RA were combined, this effect was potentiated. On the other hand, it was found that the effect of 13-cis-RA individually on neuroblastoma cells was very slight. CONCLUSION: We suggest that in the treatment of patient with neuroblastoma, MLT is very effective and also this effect can be augmented by combination with 13-cis-RA.

Combination of internal and external use of Chinese material medica with syndrome differentiation in treating 200 cases of acne vulgaris / 中华中医药杂志

Objective:To observe the effect of internal and external use of Chinese material medica with syndrome differentiation on acne vulgaris.Methods:200 patients with acne vulgaris were randomly divided into treatment group(110 cases)and control group(90 cases).Treatment group were given acne facial mask,oral medicine decoction,and the control group were treated with13-cis-Retinoic Acid Capsules,topical Clindamycin Gel,7 weeks for a course of treatment,the clinical effect were compared.Results:The effect on facial lesion in treatment group and control group had significant difference(P

Allogeneic Hematopoietic Stem Cell Transplantation in Juvenile Myelomonocytic Leukemia / 소아과

PURPOSE: The purpose of this study was to evaluate the outcome of children with juvenile myelomonocytic leukemia(JMML) treated with allogeneic hematopoietic stem cell transplantation(allo- HSCT). METHODS: Eleven JMML patients aged 8-39 months underwent allo-HSCT. The sources of grafts were unrelated donors(n=7), HLA-matched siblings(n=3) and an HLA 1-antigen mismatched familial donor. All patients had received chemotherapy +/- 13-cis-retinoic acid(CRA) before transplant, and CRA was used, posttransplant, in six patients. RESULTS: Only three patients were in complete remission(CR) at the time of transplantation. Initial chimeric status revealed complete donor chimerism(CC) in five patients, mixed chimerism(MC) in five and autologous recovery(AR) in one. One patient with MC having persistent splenomegaly eventually turned to CC and CR after rapid tapering of cyclosporine, combined with daily use of CRA. An AR case relapsed shortly after transplant but was rescued with second, unrelated cord blood transplantation. Ultimately, six patients are alive, event-free, with a median follow-up of 15.5 months posttransplant. All three deaths occurred in patients who failed to achieve CC, leading to disease progression. CONCLUSION: We suggest that graft-versus-leukemia effect play an important role and CRA a possible role in posttransplant leukemic involution in JMML. In patients whose leukemic burden is still high with MC after transplant, early tapering of immunosuppressants and introduction of CRA might provide a chance of a cure for some patients.

The Effect of Retinoids in Medulloblastoma Cell Culture

The retinoic acid, one of the most popular agents for chemoprevention can inhibit the proliferation of many cancer cells including neuroblastoma and glioblastoma but there is increasing demand reaccessing its in vitro inhibitory effect on the tumor proliferation because of poor responsiveness from recent clinical trial for malignant brain tumor with retinoic acid. If was known to effect on tumor cells by diffferentiation and apoptosis so that its effect was expected greater in pediatric brain tumor than in adult brain tumor, but there is no report on the effect of retinoic acid in medulloblastoma cell proliferation except all-trans and 13-cis retinoic acid. Therefore, we compared the effects of all-trans, 13-cis, and 9-cis retinoic acid and N-(4-hydroxyphenyl) retinamide to inhibit proliferation of medulloblastoma tumor cells. Medulloblastoma cells were derived from primary culture of patient's specimen. We estimated the rate of growth inhibition of each tumor cells using MTT assay in the concentration from 10-12 M to 10-5 M of all-trans, 13-cis, and 9-cis retinoic acid and N-(4-hydroxyphenyl) retinamide. Medulloblastoma cells showed more than 30% growth inhibition by all-trans, 12% by 13-cis, 20% by 9-cis retinoic acid and 7% by N-(4-hydroxyphenyl) retinamide at 14 days culture on the concentration of 10-6M. In conclusion, significanty and dramatic effect by, especially, all-trans retinoic acid, moderate response by 13-cis retinoic acid and variable or poor response by 9-cis retinoic acid and N-(4-hydroxyphenyl) retinamide.

The Effects of All-trans and 13-cis Retinoic Acid on C6 Cell Line Cultures

Retinoic acid has been used as a trial of chemotherapeutic agent in the field of cancer therapy and resulted some success in leukemia and breast cancer. Recently, it is being tried on the malignant astrocytoma. We evaluated the effect of all-trans and 13 cis-retinoic acid on C6 cell line cultures(14 day incubation) using MTT assay and counting of cell numbers for establishing the basis of clinical trial. The cell number counting showed 51.6% and 43.1% of control in the cell number at 10 -6M concentration of all-trans and 13 cis-retinoic acid. MTT assay showed 56.4% and 46.1% of control in the optical absorbance at 10 -6M concentration of all-trans and 13 cis-retinoic acid. These results indicate the possiblity of both drug as effective chemotherapeutic agents for glial cell tumors but in-vivo study will be needed for clinical trial.

A Case of Inflammatory Linear Verrucous Epidermal Nevus

Inflammatory linear verrucous epidermal nevus(ILVEN) is a relatively rare skin disorder, characterized by chronic inflammatory psoriasiform pattern. This chronic skin disorder is generally believed to be resistant to various treatments, although some authors have reported success with 13-cis-retinoic acid and 585 nm pulsed laser therapy. We experienced a 15-month aged female ILVEN patient who has been suffered from linear erythematous verrucous pathes mainly located on left inguinal area, hand, and foot with persistent itching sense. This skin lesion have been developed at birth, and more spread out toward right extremity after 1 year old age . We initially treated this skin lesion with topical corticosteroids and oral anti-histamines, but this treatment was not successful. So we retreated this patient with etretinate(oral retinoid) and topical 13-cis-retinoic acids, we found that therapeutic responses to these applications were more remarkable. Now, we closely observe this patient's clinical course further more.

Interferon-alpha2a, 13-cis-retinoic Acid and Radiotherapy for Locally Advanced Squamous Carcinoma of the uterine Cervix: Preliminary Study / 대한부인종양콜포스코피학회잡지

Locally advanced cancer of the uterine cervix is a major cause of death worldwide. Standard treatment with rdiolherepy for locally advanced cancer of the uterine cnvix has a response rate of less than 50%. Resently concurrent chcmoradirothcrpay has been introduced but with some contvovesy. Interferon and retinoic acid are inducible proteins which posses many hiologic activities such as, antiproliferative, immunomodulatory and antineoplastic properties. Combination of interferon and retinoic acid has produced high response rates especially for patients with squamous cell carcinoma . And they may potentiate the radiation cytotoxicity as adiosensitizer. This study was underaken to assess the clinical efficacy of combination regimen with interferon-alpha2a, 13-cis-retinoic acid and radiotherapy from Dec. 1988 to Dex. 1994 at Severance hospital Yonsei uniersity. Twenty seven patients of locally advanced squamous cell carcionma of the uterine cervix enrolled in this study are evaluated for response and toxicity. The results were as follow: 1. Preliminary results of interferon-alpha2a 13-cis-retinoic acid and radiotherapy are 46.7% of response rate(33.3% complete response)and those of concurrent chemoradiotherapy are 41.7% of response rate(46.7% complete response). 2. Major toxicity of interferon-alpha2a, 13-cis-retinoic acid and radiotherapy is fever(60.0%), and only case of grade 2 anemia and one case of grade 1 AST/ALT elevation was noted. There was no grade 3 or 4 toxicity. Systemic interferon-alpha2a, 13-cis-retinoc acid and radiotherapy is highly active, well tolerated therapy for locally advanced cervical cancer.

Interferon-alpha2a, 13-cis-retinoic Acid and Radiotherapy for Locally Advanced Squamous Carcinoma of the uterine Cervix: Preliminary Study / 대한부인종양콜포스코피학회잡지

Locally advanced cancer of the uterine cervix is a major cause of death worldwide. Standard treatment with rdiolherepy for locally advanced cancer of the uterine cnvix has a response rate of less than 50%. Resently concurrent chcmoradirothcrpay has been introduced but with some contvovesy. Interferon and retinoic acid are inducible proteins which posses many hiologic activities such as, antiproliferative, immunomodulatory and antineoplastic properties. Combination of interferon and retinoic acid has produced high response rates especially for patients with squamous cell carcinoma . And they may potentiate the radiation cytotoxicity as adiosensitizer. This study was underaken to assess the clinical efficacy of combination regimen with interferon-alpha2a, 13-cis-retinoic acid and radiotherapy from Dec. 1988 to Dex. 1994 at Severance hospital Yonsei uniersity. Twenty seven patients of locally advanced squamous cell carcionma of the uterine cervix enrolled in this study are evaluated for response and toxicity. The results were as follow: 1. Preliminary results of interferon-alpha2a 13-cis-retinoic acid and radiotherapy are 46.7% of response rate(33.3% complete response)and those of concurrent chemoradiotherapy are 41.7% of response rate(46.7% complete response). 2. Major toxicity of interferon-alpha2a, 13-cis-retinoic acid and radiotherapy is fever(60.0%), and only case of grade 2 anemia and one case of grade 1 AST/ALT elevation was noted. There was no grade 3 or 4 toxicity. Systemic interferon-alpha2a, 13-cis-retinoc acid and radiotherapy is highly active, well tolerated therapy for locally advanced cervical cancer.

A Case of Follicular Occlusion Triad / 대한피부과학회지

A case of "Follicular Occlusion Triad" associated with acne conglobata, hidradenitis suppurativa and perifolliculitis capitis abscedens et suffodiens in 40-year-old male patient is presented with brief review of literature. Widespread acne occured on the face k upper back at the age of 16. Several years later, firm & tender erythematous poorly demarcated nodules developed on the back, buttock and axilla. Also, erythematous nodules developed on temporooccipital area of the scalp. Thereafter, the skin lesions become fluctuant cystic. Some of the skin lesions healed leaving severe hypertrophic scars, and purulent materials expressed from some of persistent lesions. The patient was trested with systemic 13-cis-retinoic acid, antibiotics, corticosteroids injection and incision & drainage with considerable improvement.