PIODERMA GANGRENOSO ASSOCIADO A HEPATITE C CRÓNICA TRATADO EFICAZMENTE COM ETANERCEPT

Introduction: Pyoderma gangrenosum (PG) is an idiopathic, recurrent, neutrophilic and ulcerative skin disease. Case report: A 43-year-old man with chronic hepatitis C and drugs addiction in the past presented with a 6-months history of painful, violaceus, suppurative and necrotic ulcers on his lower extremities and any skin area inju- red by needle stick. PG was the main diagnosis proposed. Histological examination of the lesion edge demonstrated microscopic changes compatible with PG. Laboratory and radiological evaluation findings were compatible with his chronic liver disease. The patient was treated, in different moments, with systemic steroids, cyclosporine, dapsone, and thalidomide, with no satisfactory response. A complete remission was achieved with etanercept. Twelve months later, there were no signals of skin lesions, relevant hepatic damages or increase in viral load. Conclusion: Etanercept was a safe and effective therapeutic option.KEYWORDS – Pyoderma Gangrenosum; Hepatitis C, Chronic; Thalidomide; Glucocorticoids; Receptors, Tumor Necro- sis Factor; Immunoglobulin G.Introdução: O pioderma gangrenoso (PG) é uma dermatose neutrofílica, ulcerativa, recorrente e de etio-patogenia desconhecida. Caso clínico: Homem, de 43 anos, ex-toxicodependente e portador de hepatite C crónica, observado por quadro clínico com 6 meses de evolução, caracterizado por úlceras dolorosas, de fundo supurativo e necrótico, localizadas nos membros inferiores e em áreas de picadas por agulha. Colocou-se como principal hipótese de diagnóstico o PG, tendo o exame histológico do bordo da lesão demonstrado alterações compatíveis com o mesmo. A avaliação imagiológica e laboratorial evidenciou apenas alterações relacionadas com a doença hepática crónica. Foi submetido, em momentos diferentes, a tratamentos com corticóides sistémicos, ciclosporina, dapsona e talidomida, sem resposta satisfatória. Após introdução do etanercept, verificou-se remissão completa do quadro. Doze meses após introdução do anti-TNF-α, o doente encontra-se sem lesões cutâneas, alterações hepáticas relevan- tes ou elevação da carga viral. Conclusão: O etanercept mostrou-se ser uma alternativa eficaz e segura.PALAVRAS-CHAVE – Pioderma Gangrenoso; Hepatite C Crónica; Talidomida; Corticóides; Etanercept

CARCINOMA BASOCELULAR POLIPÓIDE GIGANTE DO ESCROTO

Basal cell carcinomas arising on the genitalia and over 5 cm in size are exceedingly rare. We report a case of a 60-year-old man with a lesion on the scrotum which had been slowly enlarging over the previous year. On examination he had an erythematous plaque 6.0x5.0cm in size with a pedunculated nodule. We performed an incisional biopsy. The histopathological diagnosis was basal cell carcinoma. The tumor was surgically removed. This is the second reported polypoid basal cell carcinoma occurring on the scrotum but the first scrotal giant polypoid basal cell carcinoma.KEYWORDS – Carcinoma, Basal Cell; Genital Neoplasms, Male; Scrotum; Skin Neoplasms.Os carcinomas basocelulares localizados na região genital e com diâmetro superior a 5cm são extrema- mente raros. Descrevemos um caso de um doente do sexo masculino de 60 anos de idade com uma lesão no escroto de crescimento progressivo durante um ano. Ao exame objectivo apresentava uma placa eritematosa com 6.0x5.0cm de maiores eixos com um nódulo pediculado. Foi realizada biopsia incisional cujo exame histopatológico revelou carcinoma basocelular. O tumor foi posteriormente excisado. Este é o segundo caso descrito na literatura de carcinoma basocelular polipóide do escroto, mas nesta localização o primeiro com dimensões que o permitem classificar como gigante.PALAVRAS-CHAVE – Carcinoma Basocelular; Escroto; Neoplasias Genitais Masculinas; Neoplasias da Pele

II Diretriz Brasileira de Transplante Cardíaco

Universidade de São Paulo Faculdade de Medicina Hospital das ClínicasIIHospital de Messejana Dr. Carlos Alberto Studart GomesUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaInstituto Dante Pazzanese de CardiologiaUniversidade Federal de Minas Gerais Hospital das ClínicasFaculdade de Medicina de São José do Rio PretoPontifícia Universidade Católica do ParanáIHospital Israelita Albert EinsteinInstituto Nacional de Cardiologia, Fundação Universitária do Rio Grande do Sul Instituto de CardiologiaReal e Benemérita Sociedade de Beneficência Portuguesa, São PauloHospital Pró-Cardíaco do Rio de JaneiroSanta Casa do Rio de JaneiroUNIFESP, EPMSciEL

A breakthrough on Amanita phalloides poisoning: an effective antidotal effect by polymyxin B

Amanita phalloides is responsible for more than 90 % of mushroom-related fatalities, and no effective antidote is available. a-Amanitin, the main toxin of A. phalloides, inhibits RNA polymerase II (RNAP II), causing hepatic and kidney failure. In silico studies included docking and molecular dynamics simulation coupled to molecular mechanics with generalized Born and surface area method energy decomposition on RNAP II. They were performed with a clinical drug that shares chemical similarities to a-amanitin, polymyxin B. The results show that polymyxin B potentially binds to RNAP II in the same interface of a-amanitin, preventing the toxin from binding to RNAP II. In vivo, the inhibition of the mRNA transcripts elicited by a-amanitin was efficiently reverted by polymyxin B in the kidneys. Moreover, polymyxin B significantly decreased the hepatic and renal a-amanitin-induced injury as seen by the histology and hepatic aminotransferases plasma data. In the survival assay, all animals exposed to a-amanitin died within 5 days, whereas 50 % survived up to 30 days when polymyxin B was administered 4, 8, and 12 h post-a-amanitin. Moreover, a single dose of polymyxin B administered concomitantly with a-amanitin was able to guarantee 100 % survival. Polymyxin B protects RNAP II from inactivation leading to an effective prevention of organ damage and increasing survival in a-amanitin-treated animals. The present use of clinically relevant concentrations of an already human-use-approved drug prompts the use of polymyxin B as an antidote for A. phalloides poisoning in humans.Juliana Garcia, Vera Marisa Costa, Ricardo Dinis-Oliveira and Ricardo Silvestre thank FCT-Foundation for Science and Technology-for their PhD grant (SFRH/BD/74979/2010), Post-doc grants (SFRH/BPD/63746/2009 and SFRH/BPD/110001/2015) and Investigator grants (IF/01147/2013) and (IF/00021/2014), respectively. This work was supported by the Fundacao para a Ciencia e Tecnologia (FCT) - project PTDC/DTPFTO/4973/2014 - and the European Union (FEDER funds through COMPETE) and National Funds (FCT, Fundacao para a Ciencia e Tecnologia) through project Pest-C/EQB/LA0006/2013

Biodiversity recovery of Neotropical secondary forests

Old-growth tropical forests harbor an immense diversity of tree species but are rapidly being cleared, while secondary forests that regrow on abandoned agricultural lands increase in extent. We assess how tree species richness and composition recover during secondary succession across gradients in environmental conditions and anthropogenic disturbance in an unprecedented multisite analysis for the Neotropics. Secondary forests recover remarkably fast in species richness but slowly in species composition. Secondary forests take a median time of five decades to recover the species richness of old-growth forest (80% recovery after 20 years) based on rarefaction analysis. Full recovery of species composition takes centuries (only 34% recovery after 20 years). A dual strategy that maintains both old-growth forests and species-rich secondary forests is therefore crucial for biodiversity conservation in human-modified tropical landscapes. Copyright © 2019 The Authors, some rights reserved

Inflammation as a Possible Trigger for Mitoxantrone-Induced Cardiotoxicity: An In Vivo Study in Adult and Infant Mice

Mitoxantrone (MTX) is a pharmaceutical drug used in the treatment of several cancers and refractory multiple sclerosis (MS). Despite its therapeutic value, adverse effects may be severe, namely the frequently reported cardiotoxicity, whose mechanisms need further research. This work aimed to assess if inflammation or oxidative stress-related pathways participate in the cardiotoxicity of MTX, using the mouse as an animal model, at two different age periods (infant or adult mice) using two therapeutic relevant cumulative doses. Histopathology findings showed that MTX caused higher cardiac toxicity in adults. In MTX-treated adults, at the highest dose, noradrenaline cardiac levels decreased, whereas at the lowest cumulative dose, protein carbonylation increased and the expression of nuclear factor kappa B (NF-κB) p65 subunit and of M1 macrophage marker increased. Moreover, MTX-treated adult mice had enhanced expression of NF-κB p52 and tumour necrosis factor (TNF-α), while decreasing interleukin-6 (IL-6). Moreover, while catalase expression significantly increased in both adult and infant mice treated with the lowest MTX cumulative dose, the expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and glutathione peroxidase only significantly increased in infant animals. Nevertheless, the ratio of GAPDH to ATP synthase subunit beta decreased in adult animals. In conclusion, clinically relevant doses of MTX caused dissimilar responses in adult and infant mice, being that inflammation may be an important trigger to MTX-induced cardiotoxicity

Úlcera de Marjolin associada a ulceração e osteomielite crônicas Marjolin's ulcer associated with ulceration and chronic osteomyelitis

Doente do sexo masculino, de 78 anos, portador de uma úlcera venosa crônica na perna esquerda, com cerca de 24 anos de evolução, complicada por carcinoma espinocelular. Após o estadia mento da doença, o tratamento preconizado foi amputação acima do joelho esquerdo. A úlcera de Marjolin é a transformação maligna de uma lesão ulcerosa crônica. Trata-se de um fenômeno relativamente raro. A neoplasia maligna mais frequentemente descrita na literatura é o carcinoma espinocelular, seguido do basalioma, sarcoma e melanoma. A sua patogenia permanece pouco compreendida.<br>This report describes a 78-year old male patient with a chronic venous ulcer on his left leg for the past 24 years, complicated by a squamous-cell carcinoma. After staging of the disease, the treatment administered was amputation of the leg above the knee. Marjolin's ulcer consists of the malignant transformation of a chronic ulcerative lesion. It is a relatively rare phenomenon. The malignant tumor most commonly described in the literature is squamous cell carcinoma, followed by basal-cell carcinoma, sarcoma and melanoma. The pathogenesis of Marjolin's ulcer remains to be fully clarified

Problematizando as Transições Juvenis na Saída do Ensino Médio

Resumo: Este ensaio discute as transições juvenis em tempos incertos. A crise de sentidos de algumas agências socializadoras, entre elas a escola, em seu potencial de garantir às gerações mais novas uma transição para a vida adulta, interpela educadores e gestores sobre a necessidade de reconhecerem a posição das novas gerações nas transformações sociais. Traremos para o debate alguns dos resultados de uma pesquisa realizada com jovens do campo concluintes do ensino médio e algumas categorias analíticas que demarcam as áreas de estudos sobre juventude, como culturas juvenis e sociabilidades. É significativo reconhecer que o papel da escola na inserção sociocultural e profissional do jovem está por acontecer