Effect of tert-Butylhydroquinone on the expression of nuclear factor erythroid 2-related factor 2, heme oxygenase-1 and phosphatidylinositol 3-kinase in high glucose cultured retinal Müller cells / 中华眼底病杂志

Objective To observe the effect oftert-Butylhydroquinone (tBHQ) on the expression of nuclear factor erythroid 2-related factor 2 (Nrf2),heme oxygenase (HO)-1 and phosphatidylinositol 3-kinase (PI3K) in high glucose cultured retinal Müller cells;and to investigate the anti-oxidative stress and anti-apoptotic effects oftBHQ.Methods Retinal Müller cells were divided into normal glucose group (5.5 mmol/L,N group),high glucose group (45 mmol/L,HG group) and tBHQ intervention group (HG+tBHQ group).After retinal Müller cells were cultured with high glucose for 48 hours,the pretreatment with tBHQ (20 μmol/L) induced the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and HO-1.The Müller cells were identified by immunofluorescence staining.The expressions of Nrf2,HO-1,PI3K,B-cell lymphoma-2 (Bcl-2) and Bax were detected by Western blot and real-time fluorescence quantitative PCR.Flow cytometry was used to detect the apoptosis of retinal Müller cells in rats.Results Müller cytoplasm and nucleus GS showed strong positive,large cell body,abundant cytoplasm,uniform green fluorescence;nuclear DAPI staining round or oval,clear boundary.The expression of Nrf2 protein (t=4.114,P=0.006),HO-1 protein (t=9.275,P=0.000),Nrf2 mRNA (t=7.292,P=0.000) and HO-1 mRNA (t=15.014,P=0.000) in the HG group were higher than those in the N group.The expressions of Nrf2 protein (t=7.847,P=0.000),HO-1 protein (t=7.947,P=0.000),PI3K protein (t=5.397,P=0.002),Bcl-2 protein (t=6.825,P=0.000),Nrf2 mRNA (t=18.046,P=0.000),HO-1 mRNA (t=39.458,P=0.000),PI3K mRNA (t=4.979,P=0.003) and Bcl-2 mRNA (t=9.535,P=0.000) in the HG+tBHQ group were significantly higher than those in the HG group.The protein and mRNA expressions of Bax protein in the HG+tBHQ group were significantly lower than those in the HG group (t=14.998,16.520;P=0.000,0.000).Flow cytometry showed that the apoptosis rate of Müiller cells in the HG group was significantly higher than that in the N group (t=39.905,P=0.000).The apoptosis rate of Müller cells in the HG+tBHQ group was significantly lower than that in the HG group (t=21.083,P=0.000).Conclusion tBHQ can inhibit the apoptosis of retinal Müller cells by up-regulating the expression ofNrf2,HO-1 and PI3K.

Ocronose exógena tratada com laser de CO2 / Exogenous ochronosis treated with CO2 Laser

Ocronose exógena é doença cutânea rara, geralmente associada ao uso tópico de hidroquinona. Leva à hiperpigmentação acinzentada ou preto-azulada, devido à deposição dérmica de pigmento ocre. Não existe tratamento padronizado, e as opções terapêuticas são em geral frustrantes. Relatamos o caso de uma paciente com ocronose exógena após uso de hidroquinona, tratada com laser fracionado de CO2 e apresentando resultado bastante satisfatório.

Exogenous Ochronosis is a rare skin disease. It is usually associated with the topical use of hydroquinone, resulting in a grayish or bluish black hyperpigmentation due to dermal deposition of ocher pigment. There is no gold standard treatment and the therapeutic options are generally not effective. We report a case of a patient with exogenous achronosis after use of Hydroquinone, treated with CO2 Laser and showing very good results.

Sedum freckle capsule combined with hydroquinone cream phonophoresis in the treatment of chloasma / 国际中医中药杂志

ObjectiveTo evaluate the clinical efficacy of Sedum freckle capsule combined with hydroquinone cream phonophoresis in the treatment of chloasma.MethodsA total of 180 patients with chloasma were recruited into two groups according to the random number table, 100 in the treatment group and 80 in the control group. The patients in the control group were treated with 2% hydroquinone cream phonophoresis, and those in the treatment group received 2% hydroquinone cream phonophoresis and Sedum freckle capsules, both for 2 months. The symptom and lesion score were usedto evaluate the clinical efficacy. ResultsThe cure rates were 81.00% in the treatment group and 67.50% (χ2=4.320,P=0.038) in the control group at the end of treatment, 92.0% and 76.3% (χ2=5.538,P=0.019) at 2 months follow-up. The total lesion scores at the end of treatment and at 2 months follow-up were significantly lower than before the treatment in the treatment group (1.61 ± 0.84 and 1.30 ± 0.85vs.3.48 ± 1.02;t=14.152, 16.419, allP<0.01) and also in the control group (2.04 ± 0.61 and 2.03 ± 0.51vs.3.45 ± 1.09;t=10.097, 10.554, allP<0.01). The total lesion score at the end of treatment and at 2 months follow-up were significantly lower than in the treatment group was significantly decreased than the control group (t=3.839, 6.767; allP<0.01).ConclusionSedum freckle capsule combined with hydroquinone cream phonophoresis could effectively treat patients with chloasma.

Exogenous ochronosis: case report and literature review / Ocronose exógena: relato de caso e revisão de literatura

Exogenous ochronosis is a rare, cosmetically disfiguring condition, resulting from the longterm use of topical hydroquinone in treatment of melasma. It manifests as gray-brown or blue-black macules in hydroquinone-exposed regions. The exact incidence of ochronosis is unknown. High rates have been reported in the South African population, and it is rare in the United States. We report the case of a patient who developed exogenous ochronosis while using topical hydroquinone. It is necessary to recognize this disorder at the earliest stage and discontinue hydroquinone immediately, as its treatment is difficult. Sun exposure facilitates the formation of exogenous ochronosis and must be strictly avoided, although it is a practical problem in the tropical climate of Brazil, particularly for those who work outdoors.

Ocronose exógena é uma condição rara, cosmeticamente desfigurante, devido ao uso tópico indiscriminado de hidroquinona para tratamento do melasma. Manifesta-se como máculas marrom-acinzentadas ou preto-azuladas em áreas cutâneas do uso de hidroquinona. A exata incidência de ocronose Exógena é desconhecida. Altos índices têm sido relatados em populações sul-africanas, sendo rara nos Estados Unidos. Relatamos um caso de uma paciente que desenvolveu ocronose Exógena durante uso de hidroquinona para tratamento do melasma. É necessário o reconhecimento dessa patologia no seu estágio precoce e imediata descontinuação da droga, pois seu tratamento é difícil. A exposição solar é um fator precipitante e deve ser estritamente evitada, embora isso seja difícil no clima tropical do Brasil, especialmente para aqueles que trabalham ao ar livre.

Estudo clínico para a avaliação das propriedades clareadoras da associação de ácido kójico, arbutin, sepiwhite® e achromaxyl® na abordagem do melasma, comparada à hidroquinona 2% e 4% / Evaluation of the whitening properties of combined kojic acid, arbutin, sepiwhite® and achromaxyl® vs. 2% and 4% hydro- quinone in the treatment of melasma

Introdução: Melasma é alteração cutânea comum e adquirida, de curso prolongado e tratamento muitas vezes refratário, gerando impacto psicológico negativo na vida dos acometidos. Objetivos: Avaliar a eficácia, segurança e tolerabilidade da combinação tópica de ácido kójico, arbutin, sepiwhite® e achromaxyl ® em comparação à hidroquinona a 2% e a 4% na abordagem do melasma facial. Métodos: Estudo clínico mono-cego, comparativo, monocêntrico, com 120 voluntárias, fototipos I a IV de Fitzpatrick, entre 18 e 50 anos de idade, divididas em grupo A (n = 40; Blancy® 2 vezes ao dia), grupo B (n = 40; hidroquinona 2% à noite) e grupo C (n = 40; hidroquinona 4% à noite), que usaram os produtos durante 90 dias consecutivos. Foram realizadas avaliações clínicas (classificação e quantificação do melasma) e fotográficas, além do questionário de impacto à qualidade de vida e avaliação global deeficácia. Resultados: Cento e duas voluntárias (85%) finalizaram o estudo, (grupo A = 34, grupo B = 33, grupo C = 35). A métrica do Masi teve redução estatisticamente significante ao longo do estudo para os três Grupos (p-valor < 0,001). Conclusão: O uso tópico da associação de ácido kójico, arbutin, sepiwhite® e achromaxyl ® demonstrou ser eficaz e seguro na abordagem do melasma, apresentando-se como alternativa no arsenal terapêutico dessa dermatose recalcitrante e inestética.

Introduction: Melasma is a common, acquired, long-lasting skin disorder that is often resistant to treatment and causes negative psychological effects on patients. Objectives: To evaluate the efficacy, safety, and tolerability of the topical combination of kojic acid, arbutin, sepiwhite® and achromaxyl ® compared to 2% and 4% hydroquinone in the treatment of facial melasma. Methods: A single-blind, comparative, monocentric clinical study with 120 volunteers (aged 18-50, I to IV Fitzpatrick skin types) was conducted. The study population was divided into 3 groups: Group A (n = 40; Blancy®, 2 times a day), Group B (n = 40, 2% hydroquinone at night), and Group C (n = 40, 4% hydroquinone at night), and instructed to use the study product for 90 consecutive days. Clinical (classification and quantification of melasma) and photographic evaluations were carried out, and a questionnaire assessed the impact on the patients' quality of life and the products' general efficacy. Results: Most volunteers (n = 102, 85%) completed the study (Group A = 34, Group B = 33, Group C = 35). The Melasma Area Severity Index metrics presented a statistically significant decrease (i.e., improvement) throughout the study in all three groups (p-value < 0.001). Conclusion: The topical use of the kojic acid, arbutin, sepiwhite® and achromaxyl® combination proved to be an effective and safe alternative for treating melasma.

Associação de emblica, licorice e belides como alternativa à hidroquinona no tratamento clínico do melasma / Association of emblica, licorice and belides as an alternative to hydroquinone in the clinical treatment of melasma

FUNDAMENTOS: Melasma é uma melanodermia comum, cuja terapêutica representa um desafio clínico. OBJETIVOS: Avaliar a eficácia e segurança clínicas do complexo despigmentante emblica, licorice e belides, em comparação à hidroquinona 2 por cento, na abordagem do melasma. MÉTODOS: Após 60 dias de uso exclusivo de fotoprotetor FPS35, 56 mulheres com idades entre 18 e 60 anos, fotótipos I a IV, com melasma epidérmico ou misto, foram divididas em dois grupos de um estudo clínico monocego: A) creme contendo complexo despigmentante emblica, licorice e belides 7 por cento, usado duas vezes ao dia; B)creme de hidroquinona 2 por cento, usado à noite. O estudo durou 60 dias consecutivos e avaliações médica, das voluntárias (auto-avaliação) e fotográfica (Visia®) foram realizadas quinzenalmente. RESULTADOS: 89 por cento das voluntárias (50/56), 23 do Grupo A e 27 do Grupo B, concluíram o estudo. Duas voluntárias do Grupo A contra sete do Grupo B apresentaram eventos adversos leves transitórios. Houve despigmentação do melasma pelas avaliações médica (Grupo A: 78,3 por cento; Grupo B: 88,9 por cento) e auto-avaliação (Grupo A: 91,3 por cento; Grupo B: 92,6 por cento), todos estatisticamente significantes (p<0,001), sem diferenças entre os grupos (p>0,05). O mesmo padrão foi observado pelo Visia®, tanto no número (p = 0,001) quanto no tamanho e no tom (p<0,001), para ambos os grupos, e sem diferenças entre eles (p>0,05) nas manchas UV. CONCLUSÕES: Não houve diferença estatística na melhora do melasma nos dois grupos; o Grupo A apresentou menor incidência de eventos adversos. Logo, o complexo despigmentante emblica, licorice e belides é uma alternativa segura e eficaz na abordagem do melasma.

BACKGROUND: Melasma is a common skin pigment disorder with a difficult clinical response to treatment. OBJECTIVES: To evaluate the clinical efficacy and safety of the association of Belides, Emblica and Licorice 7 percent, compared to Hydroquinone 2 percent, in the treatment of melasma. METHODS: After 60 days of exclusive use of an SPF35 sunscreen, 56 women, 18 to 60 years of age, phototypes I to IV, with epidermal or mixed melasma, were divided into two different groups in a mono-blind clinical study: A) cream with Belides, Emblica and Licorice, applied twice a day; B) cream with Hydroquinone 2 percent, used at night. They were observed in a 60-day study; every 15 days, they were submitted to medical evaluation, self-evaluation, and photographic registration (Visia®). RESULTS: 50 volunteers (89 percent), 23 in Group A and 27 in Group B, concluded the study. Two volunteers in Group A and 7 in Group B had mild skin adverse events. Depigmentation was observed through medical evaluation (Group A: 78.3 percent; Group B: 88.9 percent) and volunteers' self-evaluation (Group A: 91.3 percent; Group B: 92.6 percent); these results were statistically significant (p<0.001), with no differences between groups (p>0.05). This pattern of results was observed by Visia® in the number (p = 0.001) and size and tone (p<0.001) of the uv stains, for both groups, with no differences between them (p>0.05). CONCLUSION: There were no statistic differences between groups in the improvement of melasma. Group A showed less skin adverse events. Therefore, the association of Emblica, Licorice and Belides is a safe and efficient alternative for the treatment of melasma.

Ocronose exógena induzida por hidroquinona: relato de quatro casos / Exogenous ochronosis hydroquinone induced: a report of four cases

A ocronose exógena é uma dermatose, aparentemente pouco frequente, caracterizada por hiperpigmentação negro-azulada fuliginosa, localizada na região onde foi aplicado o agente causador. Pode ser causada por uso de medicamentos sistêmicos, os antimaláricos e de uso tópico, como fenol, resorcinol, benzeno, ácido pícrico e a hidroquinona - que é um composto fenólico, com propriedade despigmentante, muito utilizado em formulações dermatológicas para o tratamento de melasma e outras hiperpigmentações. A fisiopatogenia deste processo ainda não está esclarecida e as abordagens terapêuticas são insatisfatórias. Relatam-se quatro casos de pacientes do sexo feminino que, após uso de preparados contendo hidroquinona, desenvolveram hiperpigmentação acentuada na face, caracterizadas no exame dermatológico e histopatológico como ocronose. Enfatiza-se a possibilidade de casos de ocronose exógena estarem sendo diagnosticados erroneamente, como falha de tratamento de melasma, e também para os riscos do uso indiscriminado de formulações, contendo hidroquinona, muitas vezes, sem acompanhamento médico.

Exogenous ochronosis is an infrequent dermatosis characterized as a dark blue hyperpigmentation localized where the causing agent was applied. It may be caused by the use of systemic medication such as antimalarials and by the use of topic substances such as phenol, resorcinol, benzene, or hydroquinone, which is a fenolic compound with depigmentation action, largely used in the treatment of melasma and other hyperpigmentation. The physiopathology of this process is not well clear up to this moment, and the therapeutic measures are not satisfactory either. Here we present four cases of female patients that developed hyperpigmentation on their faces after the use of hydroquinone containing compounds, characterized clinically and histological as ochronosi. We emphasize the possibility of exogenous ochronosis cases being misdiagnosed as a melasma treatment failure. We also emphasize the risks of the indiscriminated use of hydroquinone containing compounds, used, in many instances, without medical prescription.