Impact of Strength Training Intensity on Brain-derived Neurotrophic Factor.

The present study employed a randomized crossover design to investigate the effect of strength-training exercise at varying intensities on acute changes in plasma brain-derived neurotrophic factor (BDNF) levels. Fourteen trained male subjects (41.0±5.8 years old) were enrolled in the current study. The strength-training protocol included bench press, leg press, and lat pull-down exercises. Participants performed four sets with repetition failure at 60% or 80% of their one-repetition maximum (1RM), with a two-minute rest period. The order of intensity was randomized among volunteers. Blood samples were collected before, immediately after, and one hour after each exercise protocol. A time-point comparison revealed that a single session of strength training at 60% of 1RM increased lactate plasma concentrations from 1.2 to 16 mmol/L (p<0.0001). However, no significant changes were observed in the plasma BDNF concentration. Conversely, the training session at 80% of 1RM increased lactate concentrations from 1.3 to 14 mmol/L (p<0.0001) and BDNF concentrations from 461 to 1730 pg/ml (p=0.035) one hour after the session's conclusion. These findings support the hypothesis that a single strength-training session at 80% 1RM can significantly enhance circulating levels of BDNF.

Histopathological features of photodamage and mast cell infiltrate in actinic cheilitis with different grades of epithelial dysplasia.

BACKGROUND: Actinic cheilitis is induced by chronic exposure to ultraviolet radiation and shows solar elastosis, a feature that has been associated with mast cell infiltrates. This study aimed to investigate the area of solar elastosis, collagen loss, and mast cell infiltrates in a series of actinic cheilitis. METHODS: We evaluated the epithelial dysplasia in 52 cases of actinic cheilitis and the solar elastosis with Weigert's resorcin-fuchsin. Collagen loss was evaluated with Picrosirius red, analyzed under polarized microscopy, and scored from 1 to 3. Elastosis proportionate area (EPA) was calculated with image software. Mast cells were highlighted with toluidine blue stain. RESULTS: EPA varied from 2% to 45%, with a mean of 17.1% in the cases, with no differences among epithelial dysplasia degrees. Most cases presented collagen loss scores of 2 or 3, and higher loss of type I collagen was associated with older age. Mast cell density was higher in severe epithelial dysplasia (P = 0.002) and in high-risk cases (P = 0.01). CONCLUSION: Actinic cheilitis presented variable EPA and marked loss of type I collagen; however, these features were not associated with the degrees of epithelial dysplasia. Besides, mast cell density increased with epithelial dysplasia worsening and this was not associated with elastosis area or collagen loss.

Evaluation of epithelial dysplasia adjacent to lip squamous cell carcinoma indicates that the degree of dysplasia is not associated with the occurrence of invasive carcinoma in this site.

BACKGROUND: We analyzed the different grades of dysplasia in the epithelium adjacent to lip squamous cell carcinoma (LSCC), as a parallel to actinic cheilitis (AC) that suffered malignant transformation. METHODS: Forty samples of epithelium adjacent to LSCC were histologically graded according to the World Health Organization (WHO) and the binary systems. The expression of mutated p53 was evaluated through immunohistochemistry. RESULTS: According to WHO system, 37.5% of the cases were graded as mild, 45% as moderate and 17.5% as severe dysplasia (P = 0.09). Considering the binary system, 90% of the cases were classified as low-risk and 10% as high-risk lesions. Mutated p53 was present in 73.3% of mild, 88.8% of moderate and 71.4% of severe dysplasia cases. Considering the binary system, 80.5% of the low-risk and 75% of high-risk lesions were immunopositive; 62.5% expressed the protein in both tumor cells and adjacent epithelium; 17.5% in adjacent epithelium only, and 7.5% in LSCC islands only (P = 0.03). CONCLUSIONS: We observed heterogeneous grades of epithelial dysplasia in the epithelium adjacent to LSCC, which indicates that the analysis of AC morphological features is insufficient to predict patient's prognosis and to determine a treatment decision. Positive expression of mutant p53 in mild dysplasia reinforces this idea.

Hiperplasia Endotelial Papilífera Intravascular Oral: relato de dois casos / Oral intravascular papillary endothelial hyperplasia: two cases report

A hiperplasia endotelial papilífera intravascular (HEPI) é uma lesão vascular não neoplásica, benigna e rara, especialmente em cavidade bucal. O presente artigo relata dois casos com diferentes apresentações clínicas de HEPI, envolvendo o lábio inferior. O primeiro caso se refere a um paciente que apresentava nódulo único submucoso, endurecido, arroxeado e assintomático em mucosa labial inferior. E o segundo se reporta a uma paciente que apresentava aumento de volume assintomático em lábio inferior com a mucosa entumecida e arroxeada desde o fundo de sulco. O exame histológico revelou vasos dilatados com proliferação de células endoteliais arredondadas, associadas a estruturas papilares, de tecido conjuntivo projetadas para o lúmen vascular, associadas a um trombo organizado, no primeiro caso, e a um hemangioma, no segundo. A ausência de células inflamatórias, atipia e necrose celular excluíram outras lesões vasculares, sendo o diagnóstico final de HEPI. O prognóstico da HEPI é excelente, uma vez que recidivas são raramente relatadas. A HEPI pode ser incluída no diagnóstico diferencial clínico de lesões labiais únicas, arroxeadas e endurecidas. E por caracterizarse histologicamente por uma proliferação de células endoteliais, é importante estabelecer o diagnóstico diferencial com o angiossarcoma, uma lesão de tratamento mais agressivo e pior prognóstico... (AU)

Intravascular papillary endothelial hyperplasia (IPEH) is a nonneoplastic vascular benign and rare lesion, especially in oral cavity. This article reports two cases of IPEH, with different clinical presentation, involving the inferior lip. The first case refers to a patient presenting a single submucosal indurated purplish and asymptomatic nodule in the lower labial mucosa. And the second, to a patient presenting an asymptomatic increase in the lower lip associated with a swelling and purplish oral mucosa. Histological examination showed dilated vessels with rounded endothelial cells proliferation associated with papillary structures of connective tissue projected to vascular lumen, associated with an organized thrombus in first case and a hemangioma in the second. The absence of inflammatory cells, cytologic atypia and necrosis excluded other vascular lesions, being the final diagnosis of IPEH. The prognosis of IPEH is excellent since recurrences are rarely reported. Isolated purplish and indurated labial lesions can include the IPEH as a possible clinical hypothesis. And, since is histologically characterized by a proliferation of endothelial cells, is crucial the establishment of the histological differential diagnosis with angiosarcoma, which requires a more aggressive treatment and has worse prognosis... (AU)

Correlação entre aspectos clínicos e marcadores biológicos no processo de fotocarcinogênese de lábio / Relationship between clinical aspects and biological markers during lip photocarcinogenesis process

A queilite actínica (QA) é uma lesão potencialmente maligna importante para identificar indícios precoces de transformação maligna para o carcinoma epidermoide de lábio (CEL), possibilitando a implementação de um tratamento eficiente e menos invasivo, que promova um melhor prognóstico para os pacientes. Pesquisas recentes indicam que os métodos histopatológicos geralmente são falhos em traçar o risco de malignização de casos de QA, pois além de não demonstrar as alterações genéticas presentes nos queratinócitos, não foram realizados estudos de acompanhamento clínico para avaliar se o grau de displaia epitelial da QA está relacionado ao risco de malignização para CE. Assim, a presente pesquisa teve como objetivo caracterizar, a partir dos casos atendidos no Serviço de Patologia Cirúrgica da FOUSP, qual a diferença de perfil clínico-patológico de pacientes de QA com evolução para CEL, pacientes de QA sem informações e sinais presentes de malignização e pacientes apenas diagnosticados com CEL, e também visou analisar a expressão de Ki67 e pRb nesses três grupos. Para isso, os dados dos pacientes como idade, sexo, cor da pele, aspecto clínico da lesão fundamental, coloração, tamanho e tempo de duração das lesões foram resgatados de 998 casos e distribuídos nessas três categorias. Os resultados da análise clínico-epidemiológica revelaram que o único aspecto clínico estatisticamente significante para diferenciar pacientes apenas diagnosticados com CEL dos demais grupos foi o tempo de duração das lesões. A análise do grau de displasia epitelial nos casos de QA na amostra presente revelou que todos os pacientes de QA posteriormente diagnosticados com CEL foram classificados como lesões de alto risco, e ainda exibiram em maior frequência as atipias: aumento do número de figuras de mitose, variação anormal do tamanho do núcleo, variação anormal do tamanho da célula e alteração da relação núcleo/citoplasma, figuras de mitose anormais e aumento do número e tamanho de nucléolos. Tanto a expressão da proteína Ki-67 como da proteína pRb não demonstraram significância estatística na comparação entre os grupos do estudo. Assim, a avaliação de uma ampla série de casos revelou diferença significante no tempo de duração do CEL com relação à QA. Além disso, algumas alterações morfológicas foram observadas com maior frequência em casos de QA com evolução para CEL. No entanto, outros marcadores biológicos devem ser testados em conjunto, para tentar diagnosticar alterações precoces que levem ao desenvolvimento de CEL.

Actinic cheilitis (AC) is a potentially malignant lesion important to identify early signs of malignant transformation into lip squamous cell carcinoma (LSCC), enabling the implementation of an efficient and less invasive treatment to patients. Recent researches pointed that histopatological methods often fail to trace malignization risk in AC cases, because they are unable to identify genetic damage in keratinocytes and do not exist a clinical follow-up studie to assess if the grading of epithelial dysplasia in AC is related with the malignancy risk to LSCC development. Thus, this research aims to characterize, from cases of Surgical Pathology Service of Universidade de São Paulo, the differences in clinical and pathological profile among AC patients which had evolution to LSCC, AC patients without signs and information about malignization and patients diagnosed only with LSCC. This study also analyzed the expression of Ki-67 and pRb proteins in these three groups. To conduct this study, data as age, gender, race, fundamental lesion aspect, color, size and duration time of the lesion were collected from 998 patients. The clinical-epidemiological analysis revealed that duration time of the lesion was the statistically significant clinical feature to differentiate patients diagnosed only with LSCC from other groups. The grading of epithelial dysplasia analysis showed that all AC patients with a posterior diagnosis of LSCC were classified as high risk lesions and these cases also exhibited most frequently atypia figures as: increased number of mitotic features, abnormal variation in nuclear size, abnormal variation in cellular size, increased nuclear/cytoplasmic ratio, abnormal mitotic features and increased number and size of nucleoli. The immunohistochemical expression of both Ki-67 and pRb protein demonstrated lack of significant statistical difference among the groups. We concluded that the evaluation of a large serie of cases revealed differences in duration time of lesion in patiens only diagnoses with LSCC and some morphological criteria were most frequent in AC cases with a posterior diagnosis of LSCC. However, other biological markers must be tested together, to try to identify early steps of LSCC development.

Correlação entre aspectos clínicos e marcadores biológicos no processo de fotocarcinogênese de lábio / Relationship between clinical aspects and biological markers during lip photocarcinogenesis process

A queilite actínica (QA) é uma lesão potencialmente maligna importante para identificar indícios precoces de transformação maligna para o carcinoma epidermoide de lábio (CEL), possibilitando a implementação de um tratamento eficiente e menos invasivo, que promova um melhor prognóstico para os pacientes. Pesquisas recentes indicam que os métodos histopatológicos geralmente são falhos em traçar o risco de malignização de casos de QA, pois além de não demonstrar as alterações genéticas presentes nos queratinócitos, não foram realizados estudos de acompanhamento clínico para avaliar se o grau de displaia epitelial da QA está relacionado ao risco de malignização para CE. Assim, a presente pesquisa teve como objetivo caracterizar, a partir dos casos atendidos no Serviço de Patologia Cirúrgica da FOUSP, qual a diferença de perfil clínico-patológico de pacientes de QA com evolução para CEL, pacientes de QA sem informações e sinais presentes de malignização e pacientes apenas diagnosticados com CEL, e também visou analisar a expressão de Ki67 e pRb nesses três grupos. Para isso, os dados dos pacientes como idade, sexo, cor da pele, aspecto clínico da lesão fundamental, coloração, tamanho e tempo de duração das lesões foram resgatados de 998 casos e distribuídos nessas três categorias. Os resultados da análise clínico-epidemiológica revelaram que o único aspecto clínico estatisticamente significante para diferenciar pacientes apenas diagnosticados com CEL dos demais

grupos foi o tempo de duração das lesões. A análise do grau de displasia epitelial nos casos de QA na amostra presente revelou que todos os pacientes de QA posteriormente diagnosticados com CEL foram classificados como lesões de alto risco, e ainda exibiram em maior frequência as atipias: aumento do número de figuras de mitose, variação anormal do tamanho do núcleo, variação anormal do tamanho da célula e alteração da relação núcleo/citoplasma, figuras de mitose anormais e aumento do número e tamanho de nucléolos. Tanto a expressão da proteína Ki-67 como da proteína pRb não demonstraram significância estatística na comparação entre os grupos do estudo. Assim, a avaliação de uma ampla série de casos revelou diferença significante no tempo de duração do CEL com relação à QA. Além disso, algumas alterações morfológicas foram observadas com maior frequência em casos de QA com evolução para CEL. No entanto, outros marcadores biológicos devem ser testados em conjunto, para tentar diagnosticar alterações precoces que levem ao desenvolvimento de CEL.

Actinic cheilitis (AC) is a potentially malignant lesion important to identify early signs of malignant transformation into lip squamous cell carcinoma (LSCC), enabling the implementation of an efficient and less invasive treatment to patients. Recent researches pointed that histopatological methods often fail to trace malignization risk in AC cases, because they are unable to identify genetic damage in keratinocytes and do not exist a clinical follow-up studie to assess if the grading of epithelial dysplasia in AC is related with the malignancy risk to LSCC development. Thus, this research aims to characterize, from cases of Surgical Pathology Service of Universidade de São Paulo, the differences in clinical and pathological profile among AC patients which had evolution to LSCC, AC patients without signs and information about malignization and patients diagnosed only with LSCC. This study also analyzed the expression of Ki-67 and pRb proteins in these three groups. To conduct this study, data as age, gender, race, fundamental lesion aspect, color, size and duration time of the lesion were collected from 998 patients. The clinical-epidemiological analysis revealed that duration time of the lesion was the statistically significant clinical feature to differentiate patients diagnosed only with LSCC from other groups. The grading of epithelial dysplasia analysis showed that all AC patients with

a posterior diagnosis of LSCC were classified as high risk lesions and these cases also exhibited most frequently atypia figures as: increased number of mitotic features, abnormal variation in nuclear size, abnormal variation in cellular size, increased nuclear/cytoplasmic ratio, abnormal mitotic features and increased number and size of nucleoli. The immunohistochemical expression of both Ki-67 and pRb protein demonstrated lack of significant statistical difference among the groups. We concluded that the evaluation of a large serie of cases revealed differences in duration time of lesion in patiens only diagnoses with LSCC and some morphological criteria were most frequent in AC cases with a posterior diagnosis of LSCC. However, other biological markers must be tested together, to try to identify early steps of LSCC development.

Avaliação das atipias epiteliais, graduação das displasias e presença de proteína p53 mutada no epitélio adjacente a carcinomas epidermoides de lábio / Evaluation of epithelial atypia, degree of dysplasia and presence of mutated p53 protein in the epithelium adjacent to lip squamous cell carcinomas

O carcinoma epidermoide de lábio (CEL), que é causado pela exposição crônica e excessiva à radiação ultravioleta do sol, é precedido por uma desordem potencialmente maligna, a queilite actínica (QA). No entanto, ainda não é possível determinar quais casos de QA evoluirão para CEL. O método mais utilizado por patologistas para prever o prognóstico de desordens potencialmente malignas é a graduação histológica das displasias epiteliais. Entretanto, o sistema é subjetivo e ineficiente quanto ao seu valor preditivo. Acredita-se que o epitélio adjacente ao CEL tenha alterações genéticas semelhantes ao corpo da neoplasia. O objetivo deste estudo foi graduar as displasias epiteliais na margem do CEL e verificar a presença de proteína p53 mutada nessas áreas. Foram utilizados 40 casos de CEL com epitélio adjacente, no qual a displasia epitelial foi classificada pelo sistema proposto pela Organização Mundial da Saúde (OMS) e pelo sistema binário. Os casos foram, ainda, submetidos a reações de imuno-histoquímica com anticorpo anti-proteína p53 mutada. Entre os 40 casos estudados, 15 apresentaram displasia epitelial discreta, 18 moderada e 7 intensa. Pelo sistema binário, 36 casos foram classificados como de baixo risco e 4 como de alto risco. A marcação imuno-histoquímica para a proteína p53 mutada foi encontrada no epitélio adjacente de 32 casos (80%) dessa amostra. Considerando-se as duas graduações estudadas, a marcação foi detectada em 11/15 casos de displasia discreta, 16/18 de moderada e 5/7 de intensa pelo sistema da OMS e em 29/36 casos de baixo risco e 3/4 casos de alto risco. Concluiu-se, assim, que o epitélio adjacente ao CEL, mesmo exibindo poucas alterações morfológicas pode ter um comprometimento genético importante em genes que comandam a estabilidade genômica.

The lip squamous cell carcinoma (LSCC), which is caused by chronic and excessive exposure to solar ultraviolet radiation, is preceded by a potentially malignant disorder, the actinic cheilitis (AC). However, it is not possible to determine which AC cases will progress to LSCC. The method used by pathologists to predict the prognosis of potentially malignant disorders is the histologic grading of epithelial dysplasia. Nevertheless, this system is subjective and inefficient as to its predictive value. It is considered that the epithelium adjacent to LSCC has genetic alterations similar to the main tumor. The aim of this study was to grade the epithelial dysplasia on the LSCC border and also to verify the presence of mutated p53 protein in these areas. Forty LSCC cases with adjacent epithelium were retrieved from our files. The epithelial dysplasia was classified by the system proposed by the World Health Organization (WHO) as well as the binary system. Three m sections were submitted to the antibody against mutated p53 protein by means of immunohistochemistry. Among the 40 cases studied, 15 were classified as mild dysplasia, 18 moderate and 7 severe. When the binary system was considered, 36 cases were classified as low risk and four as high risk. Immunostaining revealed the presence of mutated p53 protein in the adjacent epithelium of 32 cases (80%). Analyzing the two grading systems separately, the staining was detected in 11/15 cases of mild dysplasia, 16/18 of moderate and 5/7 of intense; 29/36 of low-risk cases and 3/4 cases high-risk. In conclusion, even if it shows few morphological changes, the epithelium adjacent to LSCC may have a genetic involvement in important genes that control genomic stability.