Renal histology and immunohistochemistry after acute hemorrhage in rats under sevoflurane and ketoprofen effect

OBJETIVO: Investigar a influência do inibidor não-seletivo da ciclooxigenase, cetoprofeno (ceto) intravenoso, em alterações histológicas e dos níveis das citocinas renais - fator α de necrose tumoral (TNF- α) e interleucina 1 (IL-1) - após hemorragia de 30% da volemia (10%, três vezes, em intervalos de 10 min). MÉTODOS: Sob anestesia com sevoflurano (sevo), os grupos sevo e sevo+ceto (10 ratos cada) foram preparados cirurgicamente para leitura de pressão arterial média (PAM) e administração de solução de Ringer (5 mL/kg/h) e de cetoprofeno (1,5 mg/kg), no início da anestesia, no grupo sevo+ceto. Mediu-se temperatura retal continuamente. Os valores de temperatura e PAM foram observados antes da primeira hemorragia (T1), após a terceira hemorragia (T2) e 30 min após T2 (T3). Realizada nefrectomia bilateral nos dois grupos para análise histológica e imuno-histoquímica. RESULTADOS: Nos dois grupos, temperatura e PAM diminuíram com relação aos valores basais. Hipotermia foi mais acentuada no grupo sevo (p=0,0002). Necrose tubular foi mais frequente no grupo sevo (p=0,02). As citocinas estiveram igualmente presentes nos rins dos dois grupos. CONCLUSÃO: Cetoprofeno foi mais protetor no rim de rato durante anestesia com sevoflurano e hipovolemia, porém parece que TNF- α e IL-1 não estão envolvidas nessa proteção.

Spontaneous canine transmissible venereal tumor: cell morphology and influence on P-glycoprotein expression

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Spontaneous canine transmissible venereal tumor: association between different phenotypes and the insertion LINE-1/c-myc

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

No mutations found in exons of TP53, H-RAS and K-RAS genes in liver of male Wistar rats submitted to a medium-term chemical carcinogenesis assay

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Cabergoline versus bromocriptine in the treatment of hyperprolactinemia: a systematic review of randomized controlled trials and meta-analysis

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Condroma de sela turca associado a hipopituitarismo: relato de um caso

Os condromas intracranianos são raros, sendo mais comumente encontrados na base do crânio e na região esfenoetmoidal. Nesta localização podem ser confundidos com meningiomas, neurinomas e craniofaringiomas. Os autores apresentam a evolução clínica e as características pela imagem de um paciente portador de condroma da sela turca submetido a excisão tumoral.

Actinic cheilitis and squamous cell carcinoma of the lip: clinical, histopathological and immunogenetic aspects

Queilite actínica é a principal lesão pré-neoplásica do lábio. O carcinoma espinocelular do lábio é incluído nas estatísticas brasileiras junto com os cânceres de boca e, em conjunto, somam 40% dos cânceres de cabeça e pescoço. Há certo desconhecimento médico e odontológico em geral quanto aos fatores relacionados à carcinogênese e à progressão de tumores de boca. Genes de supressão tumoral e proteínas regulatórias de proliferação celular exercem papel na evolução da queilite actínica para carcinoma espinocelular e no comportamento biológico deste. O conhecimento de marcadores de diagnóstico e prognóstico e sua investigação têm utilidade no acompanhamento de tais pacientes.

Primary cutaneous cryptococcosis in Brazil: report of 11 cases in immunocompetent and immunosuppressed patients

Background Primary cutaneous cryptococcosis is an uncommon infectious disease caused by Cryptococcus neoformans or Cryptococcus gattii affecting immunosuppressed as well as immunocompetent patients. It is often misdiagnosed as it may mimic other cutaneous diseases. Materials and methods We report a series of cases diagnosed from 2005 to 2010 in two general hospitals. The diagnosis in all patients was made on the basis of histopathology and culture. Phenoloxidase and canavanine-glycine-bromothymol blue tests were used in order to identify the Cryptococcus species. Systematic investigation ruled out the systemic involvement in every case. Results Eleven patients, 81.8% male, were diagnosed during this study. The immunosuppression status was identified in 54.5% of patients, and all of them were under corticosteroid therapy due to a variable set of diseases. All patients presented with circumscribed lesions on their upper limbs. Most lesions showed an infiltrative or tumoral aspect with up to 40 cm diameter. Fluconazole, up to 400 mg/daily, was the main therapeutic regimen and proved to be efficient. Conclusions Primary cutaneous cryptococcosis has been diagnosed in both immunosuppressed and immunocompetent patients. Its peculiar clinical aspect could facilitate early diagnosis. Culture and biochemical tests should be performed in order to define the species involved.

Efeitos da laserterapia na atividade biológica de células de carcinoma epidermóide de língua humano

The low level laser therapy (LLLT) has shown to be effective in promoting the proliferation of different cells in vitro, including keratinocytes, osteoblasts, endothelial cells and stem cells. It has been speculated that the biostimulatory effect of LLLT could cause undesirable enhancement of tumor growth in neoplastic diseases, since the malignant cells are more susceptible to proliferative stimuli. Within this context, this study evaluated the effect of LLLT on epidermoid carcinoma of the tongue cell line (SCC25) proliferation and invasion. Cultured cells were irradiated with an InGaAIP diode laser, 660nm, 30mW using two energy densities (0.5J/cm2 and 1.0J/cm2). Proliferative activity was assessed through trypan blue staining method and through cell cycle analysis using flow cytometry. The invasive potential was measured through cell invasion assay using matrigel. Cyclin D1, E-cadherin, -catenin and MMP-9 expressions were analyzed by immunofluorescence and flow cytometry and related to the investigated biological activities. Proliferation curve demonstrated that SCC25 irradiated with 1.0J/cm2 had the highest proliferative rate when compared to the control group and the group irradiated with 0.5J/cm2 (p<0.05). LLLT affected cell cycle distribution and energy density of 1.0 J/cm2 promoted a higher percentage of cells in S/G2/M phases, with statistically significant differences at 24h interval (p<0.05). LLLT, mainly with 1.0J/cm2, revealed significantly higher potential for invasion and influenced the expression of cyclin D1, E-cadherin, -catenin and MMP-9, promoting the malignant phenotype. In conclusion, our results indicate that LLLT has an important stimulatory effect on proliferation and invasion of SCC25 cells, likely due to altered expression of proteins associated with these processes

Citocinas e proteínas de fase aguda do soro como marcadores de regressão da resposta inflamatória ao tratamento da tuberculose pulmonar

OBJETIVO: Analisar o padrão de citocinas pró- e antiinflamatórias e da resposta de fase aguda (RFA) como marcadores de resposta ao tratamento da tuberculose pulmonar. MÉTODOS: Determinação dos níveis de interferon-gama (IFN-γ), tumor necrosis factor-alpha (TNF-α, fator de necrose tumoral-alfa), interleucina-10 (IL-10) e transforming growth factor-beta (TGF-β, fator transformador de crescimento-beta), pelo método ELISA, em sobrenadante de cultura de células mononucleares do sangue periférico e monócitos, assim como dos níveis de proteínas totais, albumina, globulinas, alfa-1-glicoproteína ácida (AGA), proteína C reativa (PCR) e velocidade de hemossedimentação (VHS) em 28 doentes com tuberculose pulmonar, em três tempos: antes (T0), aos três meses (T3) e aos seis meses (T6) de tratamento, em relação aos controles saudáveis, em um único tempo. RESULTADOS: Os pacientes apresentaram valores maiores de citocinas e RFA que os controles em T0, com diminuição em T3 e diminuição (TNF-α, IL-10, TGF-β, AGA e VHS) ou normalização (IFN-γ e PCR) em T6. CONCLUSÕES: PCR, AGA e VHS são possíveis marcadores para auxiliar no diagnóstico de tuberculose pulmonar e na indicação de tratamento de indivíduos com baciloscopia negativa; PCR (T0 > T3 > T6 = referência) pode também ser marcador de resposta ao tratamento. Antes do tratamento, o perfil Th0 (IFN-γ, IL-10, TNF-α e TGF-β), indutor de e protetor contra inflamação, prevaleceu nos pacientes; em T6, prevaleceu o perfil Th2 (IL-10, TNF-α e TGF-β), protetor contra efeito nocivo pró-inflamatório do TNF-α ainda presente. O comportamento do IFN-γ (T0 > T3 > T6 = controle) sugere sua utilização como marcador de resposta ao tratamento.

Expressão antigênica em carcinomas do plexo coróide humano: relato de dois casos

Neoplasias provenientes do epitélio de revestimento do plexo coróide são inco-muns, tendo sido descritos 6 padrões morfológicos. O padrão anaplásico, também denominado carcinoma do plexo coróide, é o de menor freqüência e pode dar metastases fora do SNC. A distinção histológica desses tumores, particularmente da variedade anaplásica, com outras neoplasias primárias e metastáticas no SNC pode ser difícil. O uso de técnicas imunocitoquimicas em parafina tem-se mostrado útil no esclarecimento das linhagens tumorais. Os papilomas do plexo coróide têm, no entanto, sido objeto de controvérsia, por sua complexa expressão antigênica. Usando a técnica de imunoperoxidase (sistema avidina-biotina-peroxidase) pesquisaram-se, em dois casos da variedade anaplásica, os seguintes marcadores: proteína glial fibrilar ácida (GFAP) com anticorpo monoclonal e policlonal; ceratinas de 40-50kDa, ceratinas de 60-70kDa (callus ceratina), enolase neuronal específica (NSE) e proteína S-100, com anticorpos monoclonais. Os dois tumores mostraram positividade para NSE, proteína S-100 e ceratina de 40-50kDa; uma das duas neoplasias mostrou diferenciação glial, revelando positividade para GFAP tanto com anticorpo monoclonal quanto policlonal.

DNA methylation patterns in bladder cancer and washing cell sediments: a perspective for tumor recurrence detection

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

H19-DMR allele-specific methylation analysis reveals epigenetic heterogeneity of CTCF binding site 6 but not of site 5 in head-and-neck carcinomas: A pilot case-control analysis

Aberrant methylation of seven potential binding sites of the CTCF factor in the differentially methylated region upstream of the H19 gene (H19-DMR) has been suggested as critical for the regulation of IGF2 and H19 imprinted genes. In this study, we analyzed the allele-specific methylation pattern of CTCF binding sites 5 and 6 using methylationsensitive restriction enzyme PCR followed by RFLP analysis in matched tumoral and lymphocyte DNA from head-and-neck squamous cell carcinoma (HNSCC) patients, as well as in lymphocyte DNA from control individuals who were cancer-free. The monoallelic methylation pattern was maintained in CTCF binding site 5 in 22 heterozygous out of 91 samples analyzed. Nevertheless, a biallelic methylation pattern was detected in CTCF binding site 6 in a subgroup of HNSCC patients as a somatic acquired feature of tumor cells. An atypical biallelic methylation was also observed in both tumor and lymphocyte DNA from two patients, and at a high frequency in the control group (29 out of 64 informative controls). Additionally, we found that the C/T transition detected by HhaI RFLP suppressed one dinucleotide CpG in critical CTCF binding site 6, of a mutation showing polymorphic frequencies. Although a heterogeneous methylation pattern was observed after DNA sequencing modified by sodium bisulfite, the biallelic methylation pattern was confirmed in 9 out of 10 HNSCCs. These findings are likely to be relevant in the epigenetic regulation of the DMR, especially in pathological conditions in which the imprinting of IGF2 and H19 genes is disrupted.

CDHI promoter hypermethylation and E-cadherin protein expression in infiltrating breast cancer

Background: the E-cadherin gene (CDH1) maps, at chromosome 16q22.1, a region often associated with loss of heterozygosity (LOH) in human breast cancer. LOH at this site is thought to lead to loss of function of this tumor suppressor gene and was correlated with decreased disease-free survival, poor prognosis, and metastasis. Differential CpG island methylation in the promoter region of the CDH1 gene might be an alternative way for the loss of expression and function of E-cadherin, leading to loss of tissue integrity, an essential step in tumor progression.Methods: the aim of our study was to assess, by Methylation-Specific Polymerase Chain Reaction (MSP), the methylation pattern of the CDH1 gene and its possible correlation with the expression of E-cadherin and other standard immunohistochemical parameters (Her-2, ER, PgR, p53, and K-67) in a series of 79 primary breast cancers ( 71 infiltrating ductal, 5 infiltrating lobular, 1 metaplastic, 1 apocrine, and 1 papillary carcinoma).Results: CDH1 hypermethylation was observed in 72% of the cases including 52/71 ductal, 4/5 lobular carcinomas and 1 apocrine carcinoma. Reduced levels of E-cadherin protein were observed in 85% of our samples. Although not statistically significant, the levels of E-cadherin expression tended to diminish with the CDH1 promoter region methylation. In the group of 71 ductal cancinomas, most of the cases of showing CDH1 hypermethylation also presented reduced levels of expression of ER and PgR proteins, and a possible association was observed between CDH1 methylation and ER expression ( p = 0.0301, Fisher's exact test). However, this finding was not considered significant after Bonferroni correction of p-value.Conclusion: Our preliminary findings suggested that abnormal CDH1 methylation occurs in high frequencies in infiltrating breast cancers associated with a decrease in E-cadherin expression in a subgroup of cases characterized by loss of expression of other important genes to the mammary carcinogenesis process, probably due to the disruption of the mechanism of maintenance of DNA methylation in tumoral cells.

DNA methylation patterns of the CDHI, RARB, and SFN genes in choroid plexus tumors

Genetic and epigenetic alterations in choroid plexus tumors, a rare neuroepithelial neoplasm most frequently detected in children, are poorly characterized. Epigenetic silencing associated with aberrant CpG island methylation is one mechanism leading to the loss of tumor suppressor functions in cancer cells. Using methylation-specific polymerase chain reaction, the methylation patterns of the genes CDH1 (E-cadherin), RARB (retinoic acid receptor, beta), and SFN (stratifin; 14-3-3 sigma) were retrospectively investigated in eight choroid plexus tumors (five papillomas, two atypical papillomas, and one carcinoma), as well as in two normal cortexes obtained after autopsy from male individuals aged 6 months and 64 years. Among the six pediatric tumors, the mean age at diagnosis was 1.8 years old (range, 0.2-6) and the two adult tumors were detected in a 66-year-old man and a 45-year-old woman. A high frequency of hypermethylation was detected in CDH1 and SFN genes in tumoral and normal cortex tissues. Tumor-specific RARB hypermethylation was observed in four papillomas. Further studies are required to evaluate the role of aberrant methylation in choroid plexus tumor progression. (c) 2007 Elsevier B.V. All rights reserved.