Dyschromatosis symmetrica hereditaria of late onset?

Dyschromatosis symmetrica hereditaria (DSH), also known as reticulated acropigmentation of Dohi, is an autosomal dominant disease with high penetrance, characterized by hypo- and hyperpigmented macules of varying sizes on the dorsal of the extremities with reticulated pattern. This paper presents a female patient with typical dermatological lesions, but only diagnosed in adulthood. It is necessary to perform differential diagnosis with other pigmentary disorders. This entity is not very common in South America, and the vast majority of cases were described in Japanese population. Since it is a benign disease, it is important to be aware of this diagnosis in order to establish the correct conduct for these patients.

Utility of dermoscopy for demarcation of surgical margins in Mohs micrographic surgery.

BACKGROUND: Skin cancer is the most common malignancy and can be treated in various ways. One treatment modality is Mohs micrographic surgery. Due to the increasing incidence of skin cancer in the last decades, there is a need for improvement of the Mohs technique to optimize its effectiveness. OBJECTIVE: The aim of this study was to evaluate the use of dermoscopy to guide demarcation of Mohs micrographic surgery margins and ascertain whether this method can reduce operative time and, therefore, reduce surgical morbidity and cost. METHODS AND MATERIALS: The sample comprised 44 patients who underwent Mohs micrographic surgery, allocated into two groups: the control group and the intervention group. In the latter, surgical margins were guided by dermoscopy. RESULTS: There were no statistically significant differences between the two groups by chi-square analysis (p = 0.399). CONCLUSION: Although outcomes were similar in the two groups, demonstrating that dermoscopy does not help in the demarcation of surgical margins for Mohs micrographic surgery, the study provides a practical proposal for improvement of the Mohs technique.

Utility of dermoscopy for demarcation of surgical margins in Mohs micrographic surgery

BACKGROUND: Skin cancer is the most common malignancy and can be treated in various ways. One treatment modality is Mohs micrographic surgery. Due to the increasing incidence of skin cancer in the last decades, there is a need for improvement of the Mohs technique to optimize its effectiveness. OBJECTIVE: The aim of this study was to evaluate the use of dermoscopy to guide demarcation of Mohs micrographic surgery margins and ascertain whether this method can reduce operative time and, therefore, reduce surgical morbidity and cost. METHODS AND MATERIALS: The sample comprised 44 patients who underwent Mohs micrographic surgery, allocated into two groups: the control group and the intervention group. In the latter, surgical margins were guided by dermoscopy. RESULTS: There were no statistically significant differences between the two groups by chi-square analysis (p = 0.399). CONCLUSION: Although outcomes were similar in the two groups, demonstrating that dermoscopy does not help in the demarcation of surgical margins for Mohs micrographic surgery, the study provides a practical proposal for improvement of the Mohs technique. .

Erosive adenomatosis of the nipple.

Erosive adenomatosis of the nipple is a complex benign mammary proliferation that can be misdiagnosed as a malignant mammary neoplasm. The most common clinical presentation includes discharge, erythema, erosion and crusting. The process is usually asymptomatic. It resembles benign conditions such as contact dermatitis, psoriasis and infections, but its main differential diagnosis is Paget's disease. Treatment is usually surgical and the prognosis is excellent.

Identification of a series of 4-[3-(quinolin-2-yl)-1,2,4-oxadiazol-5-yl]piperazinyl ureas as potent smoothened antagonist hedgehog pathway inhibitors.

The Hedgehog (Hh-) signalling pathway is a key developmental pathway and there is a growing body of evidence showing that this pathway is aberrantly reactivated in a number of human tumors. Novel agents capable of inhibiting this pathway are sought, and an entirely novel series of smoothened (Smo) antagonists capable of inhibiting the pathway have been identified through uHTS screening. Extensive exploration of the scaffold identified the key functionalities necessary for potency, enabling potent nanomolar Smo antagonists like 91 and 94 to be developed. Optimization resulted in the most advanced compounds displaying low serum shift, clean off-targets profile, and moderate clearance in both rats and dogs. These compounds are valuable tools with which to probe the biology of the Hh-pathway.

Adenomatose erosiva do mamilo / Erosive adenomatosis of the nipple

A adenomatose erosiva do mamilo é uma complexa proliferação benigna mamária que pode ser confundida com neoplasias malignas da mama. A apresentação típica cursa com descarga mamária, eritema, erosão e formação de crostas. O processo é geralmente assintomático e de instalação insidiosa. A adenomatose erosiva do mamilo pode ser confundida com condições benignas, como a dermatite de contato, psoríase e infecções, mas seu principal diagnóstico diferencial é a Doença de Paget. O tratamento é cirúrgico e o prognóstico, excelente.

Erosive adenomatosis of the nipple is a complex benign mammary proliferation that can be misdiagnosed as a malignant mammary neoplasm. The most common clinical presentation includes discharge, erythema, erosion and crusting. The process is usually asymptomatic. It resembles benign conditions such as contact dermatitis, psoriasis and infections, but its main differential diagnosis is Paget's disease. Treatment is usually surgical and the prognosis is excellent.

Multiplexed reporter gene assays: monitoring the cell viability and the compound kinetics on luciferase activity.

High-throughput screening assays with multiple readouts enable one to monitor multiple assay parameters. By capturing as much information about the underlying biology as possible, the detection of true actives can be improved. This report describes an extension to standard luciferase reporter gene assays that enables multiple parameters to be monitored from each sample. The report describes multiplexing luciferase assays with an orthogonal readout monitoring cell viability using reduction of resazurin. In addition, this technical note shows that by using the luciferin substrate in live cells, an assay time course can be recorded. This enables the identification of nonactive or unspecific compounds that act by inhibiting luciferase, as well as compounds altering gene expression or cell growth.

Dermatologia clínico-cirúrgica: avaliação da mudança no perfil dos procedimentos de um serviço de residência médica no Paraná-BR / Clinical-surgical dermatology: assessment of the changes in types of procedures performed in a dermatologic residency in the Brazilian State of Paraná

Introdução: Nas últimas quatro décadas a dermatologia transformou-se, de especialidade puramente clínica, em especialidade clinicocirúrgica. O dermatologista passou a realizar, além da diagnose e do tratamento clínico,o tratamento cirúrgico das afecções e neoplasias cutâneas,a correção de cicatrizes e procedimentos cutâneos necessários para melhora da aparência individual. Objetivo: Demonstrar a mudança do perfil das atividades do Serviço de Dermatologia do HC-UFPR no período estudado. Material e métodos: Foi realizada a revisão sistemática dos registros próprios do Ambulatório de Dermatologia, além dos dados fornecidos pelo Sistema de Estatística e Planejamento do HC-UFPR entre 2002 e 2007. Resultados: Houve aumento relativo de 16% no número de procedimentos cirúrgicos no período estudado, com aumento também de sua complexidade, passando o índice de exerese de lesões benignas em relação ao da exerese de tumores malignos de 2,25:1 em 2002 para 1,04:1 em 2007. Quanto aos procedimentos cosmiátricos, a realização de peelings ampliou-se 74% no período estudado. O preenchimento e a aplicação de toxina botulínica passaram de procedimentos esporádicos em 2002 para procedimentos de rotina, com 3,33 preenchimentos/mês e três aplicações toxina/mês. Conclusões: Os dados obtidos demonstram objetivamente a transformação das atividades do Serviço de Dermatologia do HC-UFPR, de principalmente clínicas, para clinicocirúrgicas, com aumento da complexidade dos procedimentos realizados no treinamento do residente de dermatologia, em concordância com a evolução da especialidade no Brasil e no mundo.

Introduction: During the last four decades, dermatology has evolved from a purely clinic into a clinical- surgical specialty. In addition to diagnosing conditions and conducting clinical therapies, dermatologists began performing surgical treatments of cutaneous affections and neoplasias, corrections of scars, and cosmetic cutaneous procedures. Objective: To describe the change in types of procedures performed at the Dermatology Service of the Clinical Hospital of the Federal University of Paraná during the period studied. Material and methods: A systematic review of the Dermatology Service's proprietary registers, and of additional data supplied by the hospital's Statistics and Planning System, was carried out for the period ranging from 2002 to 2007. Results: A relative increase of 16% in the number of surgical procedures has been verified in the study period, with an increase in the complexity of the procedures ­ with the ratio of excisions of benign lesions/ malignant tumors falling to 1.04:1 in 2007, from 2.25:1 in 2002. Among cosmetic procedures there has been a 74% increase in the application of chemical peels during this time. The use of fillers and botulinum toxin evolved from sporadic procedures in 2002 to frequent practice in 2007, with 3.33 and 3 procedures being conducted per month, respectively. Conclusions:The data, which were obtained objectively, demonstrate the transformation of the activities of the Dermatology Service of the Clinical Hospital of the Federal University of Paraná from mainly clinical to clinical- surgical procedures, with an increase in the complexity of the procedures performed to help train dermatology residents, in accordance with the development of the specialty throughout Brazil and the rest of the world.

Identification of novel, selective, and stable inhibitors of class II histone deacetylases. Validation studies of the inhibition of the enzymatic activity of HDAC4 by small molecules as a novel approach for cancer therapy.

5-Aryl-2-(trifluoroacetyl)thiophenes were identified as a new series of class II HDAC inhibitors (HDACi). Further development of this new series led to compounds such as 6h, a potent inhibitor of HDAC4 and HDAC6 (HDAC4 WT IC(50) = 310 nM, HDAC6 IC(50) = 70 nM) that displays 40-fold selectivity over HDAC1 and improved stability in HCT116 cancer cells (t(1/2) = 11 h). Compounds 6h and 2 show inhibition of alpha-tubulin deacetylation in HCT116 cells at 1 microM concentration and antiproliferation effects only at concentrations where inhibition of histone H3 deacetylation is observed.

Discovery of N-[(1-aryl-1H-indazol-5-yl)methyl]amides derivatives as smoothened antagonists for inhibition of the hedgehog pathway.

We report the synthesis and biological evaluation of N-[(1-aryl-1H-indazol-5-yl)methyl]amide derivatives as Smoothened antagonists and inhibitors of the Hedgehog pathway. Identification of the lead structure 1 by HTS, followed by SAR study on the amide and aryl portions led to the discovery of antagonists with nanomolar activity.

Studies of the metabolic stability in cells of 5-(trifluoroacetyl)thiophene-2-carboxamides and identification of more stable class II histone deacetylase (HDAC) inhibitors.

5-(Trifluoroacetyl)thiophene-2-carboxamides were found to be potent and selective class II HDAC inhibitors. This paper describes their further development and the investigation on the cause for the lack of cell-based activity. A rapid screening assay was set up which enabled the identification of more metabolic stable compounds as potent and selective class II HDAC inhibitors.

Optimization of a series of potent and selective ketone histone deacetylase inhibitors.

Histone deacetylase (HDAC) inhibitors offer a promising strategy for cancer therapy and the first generation HDAC inhibitors are currently in the clinic. Herein we describe the optimization of a series of ketone small molecule HDAC inhibitors leading to potent and selective class I HDAC inhibitors with good dog PK.

Probing the elusive catalytic activity of vertebrate class IIa histone deacetylases.

It has been widely debated whether class IIa HDACs have catalytic deacetylase activity, and whether this plays any part in controlling gene expression. Herein, it has been demonstrated that class IIa HDACs isolated from mammalian cells are contaminated with other deacetylases, but can be prepared cleanly in Escherichia coli. These bacteria preparations have weak but measurable deacetylase activity. The low efficiency can be restored either by: mutation of an active site histidine to tyrosine, or by the use of a non-acetylated lysine substrate, allowing the development of assays to identify class IIa HDAC inhibitors.

Dermatose perfurante adquirida associada à insuficiência hepática em paciente transplantado de fígado / Acquired perforating dermatosis associated with hepatic failure in a liver-transplanted patient

A dermatose perfurante adquirida é entidade clinicopatológica caracterizada por eliminação transepitelial de material dérmico degenerado, ocorrendo em muitas condições, entre elas diabetes mellitus, insuficiência renal crônica e colangite esclerosante. Relata-se o caso de paciente de 17 anos, com dermatose perfurante adquirida associada à insuficiência hepática crônica, conseqüente à complicação hepática de transplante de fígado para tratamento de sua doença de base, a glicogenose tipo I.

Acquired perforating dermatosis is characterized by transepithelial elimination of degenerated dermal substances. It occurs in many conditions, such as: diabetes mellitus, chronic renal failure and sclerosing cholangitis. This article describes a 17-year-old Caucasian female with type I glucogenosis and acquired perforating dermatosis due to chronic hepatic failure caused by hepatic complication of liver transplant.

A series of novel, potent, and selective histone deacetylase inhibitors.

Histone deacetylase (HDAC) inhibitors offer a promising strategy for cancer therapy and the first generation HDAC inhibitors are currently in clinical trials. A structurally novel series of HDAC inhibitors based on the natural cyclic tetrapeptide Apicidin is described. Selected screening of the sample collection looking for L-2-amino-8-oxodecanoic acid (L-Aoda) derivatives identified a small acyclic lead molecule 1 with the unusual ketone zinc binding group. SAR studies around this lead resulted in optimization to potent, low molecular weight, selective, non-hydroxamic acid HDAC inhibitors, equipotent to current clinical candidates.

Caso para diagnóstico / Case for diagnosis

Pseudoxantoma elástico perfurante periumbilical é distúrbio adquirido do tecido elástico, que acomete mulheres multíparas. Apresenta-se um caso dessa condição em mulher de 74 anos (G10, P10) mostrando placa amarelada de aspecto reticular com áreas constituídas por pápulas eritêmato-ceratósicas. A histologia demonstra derme reticular com fibras conjuntivas basofílicas e irregulares, além de área de hiperplasia epidérmica, com eliminação de fibras elásticas através de canal repleto de ceratina.

Lipoidoproteinose - relato de dois casos / Lipoid proteinosis - a report of two cases

A lipoidoproteinose (doença de Urbach-Wiethe) é doença autossômica recessiva rara, caracterizada pela deposição progressiva de substância hialina na pele, membranas mucosas e órgãos internos. Clinicamente, os pacientes apresentam lesões papulonodulares na face, com áreas de infiltração difusa da pele principalmente nos joelhos, cotovelos e mãos; a língua apresenta consistência firme. Infiltração da laringe produz rouquidão que pode estar presente já ao nascimento. Os autores relatam dois casos dessa doença acometendo indivíduos da mesma família (irmãos)

Micose fungóide na infância: relato de um caso / Mycosis fungoides in childhood: a case report

A micose fungóide (MF) é a forma mais comum de linfoma cutâneo de células T. É rara na infância, pois afeta principalmente idosos. Os autores apresentam um caso de MF na infância, um dos primeiros relatados na literatura latino-americana, em um menino de 7 anos de idade. O diagnóstico foi realziado na fase inicial, estágio IB. O tratamento inicial com PUVA não teve boa respota. Com a substituição pela mostarda nitrogenada tópica, houve regressão das lesões