Immunostaining of stromal CD56 cells in ovarian malignancies

SUMMARY OBJECTIVES: The aim of this study was to evaluate CD56 immunostaining in the stroma of benign and malignant ovarian epithelial neoplasms and associate the CD56 immunostaining with prognostic factors and survival in ovarian cancer. METHODS: Patients with ovarian epithelial neoplasia (n=77) were studied with a prospective cohort. The CD56 immunostaining was evaluated in the peritumoral stroma. Two groups were evaluated: benign ovarian neoplasms (n=40) and malignant ovarian neoplasms (n=37). Data were recorded for histological type and grade, International Federation of Gynecology and Obstetrics staging, molecular subtype, and lymph node metastases. Fisher's exact test and Kaplan-Meier survival curves were used, with a significance level of ≤0.05. RESULTS: We found greater CD56 stromal immunostaining in malignant neoplasms when compared to the group of benign neoplasms (p=0.00001). There was no significant difference in relation to the prognostic factors and survival. CONCLUSION: Malignant ovarian neoplasms showed higher stromal CD56 immunostaining. As the prognostic value of natural killer in ovarian cancer is controversial, knowing the specific function of each cell present both in the tumor tissue and systemically may help guide successful immunotherapies in the near future.

Different roles of helper T lymphocytes during dendritic cells vaccine in experimental breast cancer

Breast cancer is the most common women’s tumor. Treatments though effective, are often aggressive and leave the patients vulnerable to developing opportunistic infections. There is a need for less aggressive more effective new therapies. In this study, we have made an attempt to evaluate DCs immunotherapy by flow cytometry, analyzing the presence of infiltrating cells, cytokines and transcription factors in the spleens, lymph nodes and tumors of breast cancer mice undergoing immunotherapy. The 4T1 cell transfection was used to induce breast cancer in Balb/c mice aged 6 to 8 weeks. Mice were treated with 3 doses of DCs vaccine. After the treatment, animals were euthanized, the spleen, lymphnodes and tumors were removed and used to perform flow cytometry. Results have shown higher CD4+ T lymphocytes that produce IL-12 in the spleen of group treated with DCs vaccine (149,8-271,3) 172,4. Further, there was an increase in T-bet (976,1-1075) 1022 in the lymph nodes of tumor group treated with DCs and less FOXP3 (795,7 - 895) 832. Tumoral volume and the FOXP3 were decreased in the treated group. There was an increase in the transcription factor of Th1 profile, and of cytotoxic T lymphocytes, inferring a good immune response. With these observations, it can be concluded that the DC vaccine is effective in combating the development of tumors.

Giant luteinized follicular cyst of pregnancy / Cisto folicular luteinizado gigante da gestação

Functional cysts usually do not cause symptoms or require surgical intervention. We reported a 17-year-old primi-gravida, gestational age of 10 weeks and 2 days, and ultrasound showing anechoic cyst in the right parauterine re-gion without septa, with a larger diameter of 13.5cm, 632ml, and Doppler color without peripheral vascularization. The patient was oligosymptomatic during gestation. At 37 weeks and 6 days, gestation was interrupted, when the cyst had 2600 ml by ultrasonography. Fetal extraction was performed by cesarean delivery, and a large adnexal cyst visualized on the right was removed. The histopathological analysis of the surgical specimen revealed a cystic le-sion coated by luteinized cells with discrete hyperchromatic and slightly pleomorphic nuclei, with underlying fibrous stroma with sparse luteinized cells, characterizing a giant luteinized follicular cyst of pregnancy. The prevalence of ovarian masses in pregnancy is rare, usually not exceeding 5 cm in diameter, and disappearing spontaneously in the second trimester. The patient in the case report had a cyst of 632 ml, increasing in volume to 2600 ml at the time of delivery. Definitive preoperative diagnosis of ovarian masses is still difficult, and predictive criteria for malignancy include the use of tumor markers, ultrasound, and Doppler. The association of these tests should guide the clinician to define the best time for surgical intervention. The association of these tests should guide the clinician to define the best time for surgical intervention (AU)

Os cistos funcionais geralmente não causam sintomas ou requerem intervenção cirúrgica. Relatamos o caso de uma primigesta de 17 anos, idade gestacional de 10 semanas e 2 dias, e ultrassonografia mostrando cisto anecoico em região parauterina direita sem septos, com maior diâmetro de 13,5cm, volume 632ml e Doppler sem vascularização periférica. A paciente permaneceu oligossintomática durante a gestação. Com 37 semanas e 6 dias, a gestação foi interrompida, quando o cisto apresentava 2.600 ml pela ultrassonografia. A extração fetal foi realizada por cesaria-na, e um grande cisto anexial visualizado à direita foi removido. A análise histopatológica da peça cirúrgica revelou lesão cística revestida por células luteinizadas com núcleos discretamente hipercromáticos e levemente pleomór-ficos, com estroma fibroso subjacente com células luteinizadas esparsas, caracterizando cisto folicular luteinizado gigante da gravidez. A prevalência de massas ovarianas na gravidez é rara, geralmente não ultrapassam o diâmetro de 5 cm, e desaparecem espontaneamente no segundo trimestre. A paciente do relato de caso apresentou cisto de 632 ml, aumentando de volume para 2600 ml no momento do parto. O diagnóstico pré-operatório definitivo de massas ovarianas ainda é difícil, e os critérios preditivos de malignidade incluem o uso de marcadores tumorais, ultrassonografia e Doppler. A associação desses testes deve orientar o clínico para definir o melhor momento para a intervenção cirúrgica (AU)

Blood count and fasting blood glucose level in the assessment of prognosis and survival in advanced cervical cancer

SUMMARY OBJECTIVE: The objective of this study was to verify whether the parameters of the blood count and the fasting glucose level before treatment are related to prognosis and survival in cervical cancer (IIB-IVB staging). METHODS: Patients with cervical cancer (stages IIB-IVB) were evaluated (n=80). Age, parity, staging, histological grade, histological type, hemoglobin, red blood cells, hematocrit, neutrophil, lymphocyte and platelet counts, red blood cell distribution width, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, fasting glucose levels, overall survival, and disease-free survival were evaluated. The results of laboratory parameters were compared using the Mann-Whitney U test. Receiver operating characteristic curve was used to obtain the area under the curve and determine the best cutoff values for each parameter. Survival was verified by using the Kaplan-Meier method, followed by the log-rank test. The level of significance was ≤0.05. RESULTS: Regarding staging, lower hemoglobin values (p=0.0013), red blood cells (p=0.009), hematocrit (p=0.0016), higher leukocytes (p=0.0432), neutrophils (p=0.0176), platelets (p=0.0140), red blood cell distribution width (RDW) (p=0.0073), neutrophil-lymphocyte ratio (p=0.0039), platelet-lymphocyte ratio (p=0.0006), and fasting glucose level (p=0.0278) were found in IIIA-IVB compared with IIB staging. Shorter disease-free survival was associated with hemoglobin ≤12.3 g/dl (p=0.0491), hematocrit ≤38.5% (p=0.05), neutrophil-lymphocyte ratio >2.9 (p=0.0478), and platelet-lymphocyte ratio >184.9 (p=0.0207). Shorter overall survival was associated with hemoglobin ≤12.3 g/dl (p=0.0131), hematocrit ≤38.5% (p=0.0376), neutrophil-lymphocyte ratio >2.9 (p=0.0258), and platelet-lymphocyte ratio >184.9 (p=0.0038). CONCLUSION: The analysis of these low-cost and easily accessible parameters could be a way to monitor patients in order to predict treatment failures and act as early as possible.

Metastasizing leiomyoma during pregnancy

Uterine leiomyoma is a benign tumor of myometrial tissue which affects women of reproductive age. Its prevalence increases with age and has a peak incidence at the age of forty. The term "metastasizing leiomyoma" refers to a tumor of dense connective tissue and smooth myometrial muscle cells located outside the uterus. This group of tumors can metastasize to different organs, the lung being its main focus. We present the case report of a 33-year-old female gravida 3, para 1, abortus 1, at 11 weeks of pregnancy, with pelvic masses. The diagnosis was metastasizing leiomyoma during pregnancy.

Pathways of IFN-alpha Activation in Patients with Cervical Intraepithelial Neoplasia (CIN) / Vias de ativação de IFN-alfa em pacientes com Neoplasia Intraepitelial Cervical (NIC)

Abstract Objective The aim of the present study was to compare the local and systemic expression of the factors linked to the interferon alpha (IFN-α) activation pathway in different degrees of cervical intraepithelial neoplasia (CIN) and cervical cancer. Methods A total of 128 patients with CIN I, CIN II, CIN III and cervical cancer was evaluated. The real-time polymerase chain reaction (RT-PCR) technique was used to evaluate the gene expression of IFNR1, IFNR2, IFN-α, oligoadenylate synthase (2'5′OAS), cytokine signal suppressor 1 (SOCS) 1, SOCS3, signal transducer and transcription activator 1 (STAT1), and IRF9 from 128 biopsies. A total of 46 out of 128 samples were evaluated by flow cytometry for IFNAR1, IFNAR2, STAT1, IRF7 and IFN-α in peripheral blood cells. Results Patients with CIN II and III (63 samples) had a low local expression of IFNR1, but not IFNR2. Patients with some degree of injury showed high expression of SOCS1 and SOCS3. Systemically, patients with CIN II and III (20 samples) had a significant increase in IFNR1, IFNR2, STAT1, IRF7, and IFN-α in helper, cytotoxic T lymphocytes, and in monocytes. Conclusion Patients with high-grade lesions have increased systemic expression of IFN-α and its activation pathways in helper and cytotoxic T lymphocytes, as well as in monocytes due to an exacerbation of the immune response in these patients. This phenomenon is not accompanied by resolution of the lesion due to a defect in the IFN-α activation pathway that revealed by low local IFNAR1 expression and high local expression of SOCS1 and SOCS3.

Resumo Objetivo O objetivo do presente estudo foi comparar a expressão local e sistêmica dos fatores ligados à via de ativação do interferon alfa (IFN-α) em diferentes graus de neoplasia intraepitelial cervical (NIC) e câncer cervical (CA) Métodos Foram avaliados 128 pacientes com NIC I, NIC II, NIC III e CA. A técnica de reação de cadeia de polimerase em tempo real (RT-PCR, na sigla em inglês) foi realizada para avaliar a expressão gênica do receptor de interferon (IFNR) 1, IFNR2, IFN-α, 2′-5′- oligoadenilato sintetase (2′5′OAS), supressor de sinalização de citocina (SOCS)1, SOCS3, transdutor de sinal e ativador de transcrição 1 (STAT1) e fator regulador de interferon 9 (IRF9) das 128 biópsias. Das 128 amostras, 46 foram avaliadas por citometria de fluxo para IFNAR1, IFNAR2, STAT1, IRF7 e IFN-α em células de sangue periférico. Resultados Pacientes com NIC II e III (63 amostras) tiveram baixa expressão local de IFNR1 mas não de IFNR2. Pacientes com algum grau de lesão apresentaram alta expressão de SOCS1 e SOCS3. Sistemicamente, os pacientes com NIC II e III (20 amostras) tiveram um aumento significativo de IFNR1, IFNR2, STAT1, IRF7 e IFN-α em linfócitos T auxiliares, citotóxicos e monócitos. Conclusão Pacientes com lesões de alto grau apresentam expressão sistêmica aumentada de IFN-α e suas vias de ativação em linfócitos T auxiliares e citotóxicos, bem como em monócitos, devido à exacerbação da resposta imune nesses pacientes. Este fenômeno não é acompanhado pela resolução da lesão devido a um defeito na via de ativação do IFN-α que é revelado pela baixa expressão local de IFNR1 e alta expressão local de SOCS1 e SOCS3.

Interferon-α action in cytokine profile in eosinophilic nasal polyp cultures / Ação do interferon-α sobre o perfil de citocinas em culturas de pólipos nasais eosinofílicos

Abstract Introduction Chronic rhinosinusitis is currently classified into two types: chronic rhinosinusitis without nasal polyps and chronic rhinosinusitis with nasal polyps. In the West, approximately 80% of chronic rhinosinusitis with nasal polyps cases are characterized by a predominantly eosinophilic cell infiltrate and a Th2 cytokine pattern. Objective To evaluate the effect of Interferon-α on cytokine levels of the eosinophilic nasal polyp cell culture supernatant. Methods Cell cultures were performed based on nasal polypoid tissue samples collected from 13 patients with eosinophilic chronic rhinosinusitis with nasal polyps. Polyps were considered eosinophilic according to the histopathological examination. Cell cultures were stimulated with 3000 IU of interferon-α. Before and after the stimulus, concentrations of Interferon-γ, tumor necrosis factor αand IL 2, 4, 6 and 10, using cytometric bead array, were assessed. Results Cell samples from eosinophilic nasal polyps from 13 patients were included in the study. Twenty-four hours after interferon-α stimulation, eosinophilic nasal polyp culture supernatants showed significantly decreased IL-4 concentrations and increase in interferon-γ, IL-10 and IL-6 concentrations compared to controls. There were no significant differences in tumor necrosis factor -α and IL-2 concentrations. Conclusion We demonstrated that interferon-α in vitro alters the pattern of cytokines in cell cultures of eosinophilic nasal polyps. Analysis of these alterations suggests that interferon-α promotes a rebalancing of inflammatory profiles in cell cultures, favoring the expression of Th1 and regulatory cytokines over Th2 cytokines.

Resumo Introdução A rinossinusite crônica, atualmente, é classificada em dois tipos: Rinossinusite Crônica sem Pólipos Nasais (RSCsPN) e Rinossinusite Crônica com Pólipos Nasais (RSCcPN). No Ocidente, cerca de 80% dos casos de RSCcPN caracterizam-se por um infiltrado celular predominantemente eosinofílico e um padrão de citocinas Th2. Objetivo Avaliar o efeito do Interferon-alpha nos níveis de citocinas do sobrenadante de culturas celulares de pólipos nasais eosinofílicos. Método Foram feitas culturas celulares a partir de amostras de tecido polipoide nasal coletadas de 13 pacientes com RSCcPN eosinofílica. Os pólipos eram considerados eosinofílicos segundo exame histopatológico. As culturas celulares foram estimuladas com 3000 UI de IFN-α. Antes e após tal estímulo, foram avaliadas, no sobrenadante das culturas celulares, as concentrações do Interferon-γ (IFN-γ), do Fator de Necrose Tumoral alfa (TNF-α) e das Interleucinas (IL) 2, 4, 6 e 10, usou-se o Cytometric Bead Array. Resultados Foram incluídas no estudo amostras celulares dos pólipos nasais eosinofílicos de 13 pacientes. Vinte e quatro horas após o estímulo com IFN-α, os sobrenadantes das culturas dos pólipos nasais eosinofílicos apresentaram, de forma significante, diminuição da concentração de IL-4 e aumento das concentrações de IFN-γ, IL-10 e IL-6, em relação ao controle. Não houve diferença significante nas concentrações de TNF-α e IL-2. Conclusão Demonstramos que o IFN-α, in vitro, altera o padrão de citocinas nas culturas celulares de pólipos nasais eosinofílicos. A análise do conjunto dessas alterações sugere que o IFN-α promove, nas culturas celulares, um rebalanceamento dos perfis inflamatórios, favorece a expressão de citocinas Th1 e regulatórias, em detrimento de citocinas do padrão Th2.

Immunological Characteristics between αß TDC and γδ TDC Cells in the Spleen of Breast Cancer-Induced Mice / Características imunológicas entre células TDC αß e TDC γδ no baço de camundongos com câncer de mama induzido

Abstract Objective To evaluate the antitumoral role of γδ TDC cells and αβ TDC cells in an experimental model of breast cancer. Methods Thirty female Balb/c mice were divided into 2 groups: control group (n=15) and induced-4T1 group (n=15), in which the mice received 2 x 105 4T1 mammary tumor cell line. Following the 28-day experimental period, immune cells were collected from the spleen and analyzed by flow cytometry for comparison of αβ TDC (TCRαβ+ CD11c+MHCII+) and γδ TDC (TCRγδ+CD11c+MHCII+) cells regarding surface markers (CD4+ and C8+) and cytokines (IFN-γ, TNF-α, IL-12 and IL-17). Results A total of 26.53% of γδ TDC- control group (p<0.0001) - the proportion of αβ TDC was lower in splenic cells than γδ TDC; however, these 2 cell types were reduced in tumor conditions (p<0.0001), and the proportion of IFN-γ, TNF-α, IL-12 and IL-17 cytokines produced by γδ TDC was higher than those produced by αβ TDC, but it decreased under conditions of tumor-related immune system response (p<0.0001). Conclusion Healthy mice engrafted with malignant cells 4T1 breast tumor presented TDC with γδ TCR repertoire. These cells express cytotoxic molecules of lymphocytes T, producing anti-tumor proinflammatory cytokines.

Resumo Objetivo Esclarecer o possível papel antitumoral das células TDC γδ e TDC αβ em um modelo experimental de câncer de mama. Métodos Trinta baços de camundongos Balb/c analisados por citometria de fluxo, separados entre grupo controle (n=15) e o grupo tumoral induzido por 4T1 (n=15). Resultados Presença de 26,53% de TDC γδ nos camundongos do grupo controle (p<0,0001), proporção de TDC αβ menor em células esplênicas do que TDC γδ; no entanto, estes dois tipos de células são reduzidos emcondições tumorais (p<0,0001), e a proporção de citocinas IFN-γ, TNF-α, IL-12 e IL-17 produzidas pelas célula TDC γδ foi maior do que as produzidas pelas células TDC αβ, mas foram diminuídas sob condições de resposta ao sistema imunológico relacionada ao tumor (p<0,0001). Conclusão Camundongos saudáveis induzidos ao tumor de mama 4T1 apresentaram TDC com repertório TCR γδ. Estas células expressam moléculas citotóxicas de linfócitos T, produzindo citocinas proinflamatórias anti-tumor.

Qualidade de vida sexual de mulheres no pós-tratamento radioterápico de câncer de colo uterino / Sexual quality of life of women after cervical cancer radiotherapy

A qualidade de vida sexual é frequentemente afetada após tratamento oncológico em ginecologia. Reportamos a qualidade de vida sexual de pacientes em seguimento no serviço de Oncologia Ginecológica da Universidade Federal do Triângulo Mineiro, por meio da aplicação do questionário validado FSFI (Female Sexual Function Index), comparando pacientes diagnosticadas com câncer de colo uterino que receberam tratamento radioterápico com aquelas que foram submetidas a tratamento para câncer de colo uterino no qual não foi necessária a realização de radioterapia. Foi realizada análise estatística utilizando os testes D'Agostino-Pearson e o teste não paramétrico Mann-Whitney. Concluiu-se que a diminuição do desejo e da excitação foi mais frequente nas mulheres tratadas com radioterapia e que não houve diferença significativa entre as pacientes a respeito de lubrificação, orgasmo, satisfação e dispareunia.(AU)

Quality of sexual life is often affected after oncological treatment in gynecology. We report the quality of sexual life of patients in a follow-up at the Gynecological Oncology service of the Federal University of Triângulo Mineiro, through the application of a questionnaire validated in the Portuguese language. The purpose of this study was to compare cervical cancer patients diagnosed who received radiotherapy with those who have been submitted to treatment for cervical cancer in which it was not necessary to perform radiotherapy. Decreased desire and arousal were more frequent in women treated with radiotherapy. Statistical analysis was performed using the D'Agostino-Pearson tests and the non-parametric Mann-Whitney test. It was concluded that decreased desire and arousal were more frequent in women treated with radiotherapy, and that there was no significant difference between patients regarding lubrication, orgasm, satisfaction and dyspareunia.(AU)

Laboratory predictors of survival in ovarian cancer

SUMMARY OBJECTIVE To relate disease-free survival and overall survival with type I and type II ovarian cancer and preoperative laboratory parameters biomarkers. METHODS A retrospective study was carried out based on the collection of data from medical records of patients with ovarian tumors. Kaplan-Mayer curves were drawn based on the statistical analysis of the data and were compared using the Log-rank test. RESULTS Disease-free survival in type I ovarian cancer was significantly higher than in type II (p=0.0013), as well as in those with normal levels of CA-125 (p=0.0243) and with a platelet-lymphocyte ratio (PLR) lower than 200 (p=0.0038). The overall survival of patients with type I ovarian cancer was significantly higher than in patients with type II, as well as in patients with normal CA-125 serum levels (p=0.0039) and those with a preoperative fasting glucose of less than 100 mg/dL. CONCLUSION CA-125 levels may predict greater overall and disease-free survival. PLR < 200 may suggest greater disease-free survival, whereas normal fasting glucose may suggest greater overall survival.

RESUMO OBJETIVO Relacionar a sobrevida livre de doença e sobrevida global com câncer de ovário tipos I e II, assim como com parâmetros laboratoriais pré-operatórios biomarcadores. MÉTODOS Estudo retrospectivo realizado com base na coleta de dados de prontuários de pacientes com tumor ovariano. As curvas de Kaplan-Mayer foram realizadas em relação à análise estatística dos dados, sendo comparadas pelo teste de Log-rank. RESULTADOS A sobrevida livre de doença nas pacientes com câncer de ovário tipo I foi significativamente maior do que nas pacientes com câncer de ovário tipo II (p = 0,0013), bem como maior naquelas com níveis normais de CA-125 (p = 0,0243) e com relação plaquetas-linfócitos (RPL) inferior a 200 (p = 0,0038). A sobrevida global de pacientes com câncer de ovário tipo I foi significativamente maior do que em pacientes com tipo II, maior em pacientes com níveis séricos normais de CA-125 (p = 0,0039) e naquelas com glicemia de jejum pré-operatória menor que 100 mg / dL. CONCLUSÃO Os níveis de CA-125 podem predizer uma sobrevida global e livre de doença. A RPL < 200 pode sugerir uma maior sobrevida livre de doença, enquanto uma glicemia normal de jejum, uma maior sobrevida global.

Is ovarian cancer prevention currently still a recommendation of our grandparents? / A prevenção do câncer de ovário ainda é uma recomendação de nossos avós?

Abstract Ovarian cancer is the leading cause of death among gynecologic tumors because in most of the cases (75%), the disease is diagnosed in advanced stages. Screening methods are not available since the disease is rare, and the tested methods, such as ultrasound and CA125, were not able to decrease the mortality rate for this type of cancer. This article discusses the main risk factors for ovarian cancer, and the potential clinical and surgical strategies for the prevention of this disease.

Resumo O câncer de ovário é a principal causa de morte entre os tumores ginecológicos, já que na maioria dos casos (75%) o diagnóstico ocorre em estádios avançados. Métodos de rastreamento não estão disponíveis, já que a doença é rara, e osmétodos diagnósticos, como ultrassonografia e CA 125, não são capazes de reduzir a taxa de mortalidade desse câncer. Este artigo discute os principais fatores de risco para o câncer de ovário e as possíveis estratégias clínicas e cirúrgicas para a prevenção dessa doença.

Characterization of inflammatory markers associated with systemic lupus erythematosus patients undergoing treatment / Caracterização de marcadores inflamatórios associados a pacientes com lúpus eritematoso sistêmico em tratamento

ABSTRACT Objective: To characterize the inflammatory profiles of patients with systemic lupus erythematosus receiving standard treatment compared to healthy controls. Patients and methods: Peripheral venous blood was collected from systemic lupus erythematosus patients (n = 14) and controls (n = 18) at enrollment. Blood samples were used for quantification, by flow cytometry, of CD11b (integrin) and Chemokine receptor CXCR2 expression surface antigen in neutrophils and lymphocytes, while cytokines were assayed in serum samples. Purified neutrophils were assayed by their ability to phagocytize human plasma-opsonized zymosan. Results: Patients had a median (interquartile range) disease activity index of 1.0 (0-2.0) characteristic of patients in remission. Interleukin-6 and interleukin-10 serum concentrations were significantly higher in the patient group compared to controls and the phagocytic index of circulating neutrophils was significantly reduced in patients compared to controls. The levels of interleukin-2, interleukin-5, interleukin-8 and tumor necrosis factor alpha did not significantly differ between patients and controls. Flow cytometric analysis revealed that the integrin expression levels were reduced in lymphocytes (but not in neutrophils) obtained from systemic lupus erythematosus patients, while surface expression of the chemokine receptor 2 was similar in both neutrophils and lymphocytes. Conclusion: Systemic lupus erythematosus patients receiving standard treatment presented with elevated systemic levels of interleukin-6 and interleukin-10, reduced neutrophil phagocytic capacity, and reduced lymphocyte expression of integrin even when symptoms were in remission. These alterations to innate immune components may put these individuals at a greater risk for acquiring infections.

RESUMO Objetivo: Caracterizar os perfis inflamatórios de pacientes com lúpus eritematoso sistêmico (LES) que recebiam o tratamento padrão em comparação com controles saudáveis. Pacientes e métodos: Coletou-se o sangue venoso periférico de pacientes com LES (n = 14) e controles (n = 18) no momento da entrada no estudo. As amostras de sangue foram usadas para quantificação, por citometria de fluxo, da expressão dos antígenos de superfície CD11b (integrina) e CXCR2 em neutrófilos e linfócitos, enquanto as citocinas foram avaliadas em amostras de soro. Avaliou-se a capacidade dos neutrófilos purificados de fagocitar zimosan opsonizado com plasma humano. Resultados: Os pacientes apresentavam uma pontuação mediana (intervalo interquartil) no Sledai de 1 (0-2), característica de pacientes em remissão. As concentrações séricas de IL-6 e IL-10 foram significativamente maiores no grupo de pacientes em comparação com os controles; o índice de fagocitose de neutrófilos circulantes estava significativamente reduzido nos pacientes em comparação com os controles. Os níveis de IL-2, IL-5, IL-8 e TNF-α não diferiram significativamente entre pacientes e controles. A análise da citometria de fluxo revelou que os níveis de expressão de CD11b estavam reduzidos nos linfócitos (mas não nos neutrófilos) obtidos de pacientes com LES, enquanto a expressão do receptor de superfície CXCR2 foi semelhante em neutrófilos e linfócitos. Conclusão: Os pacientes com LES que recebiam tratamento padrão apresentaram níveis sistêmicos elevados de IL-6 e IL-10, redução na capacidade fagocítica dos neutrófilos e redução da expressão de CD11b em linfócitos, mesmo quando os sintomas estavam em remissão. Essas alterações nos componentes da imunidade inata podem colocar esses indivíduos em maior risco de adquirir infecções.

Loss of Ovarian Function Results in Increased Loss of Skeletal Muscle in Arthritic Rats / Perda da função ovariana resulta em perda de músculo esquelético aumentada em ratos artríticos

Objective We studied the effects of loss of ovarian function (ovariectomy) onmuscle mass of gastrocnemius and themRNA levels of IGF-1, atrogin-1, MuRF-1, andmyostatin in an experimental model of rheumatoid arthritis in rats. Methods We randomly allocated 24 female Wistar rats (9 weeks, 195.3±17.4 grams) into four groups: control (CT-Sham; n = 6); rheumatoid arthritis (RA; n = 6); ovariectomy without rheumatoid arthritis (OV; n = 6); ovariectomy with rheumatoid arthritis (RAOV; n = 6). We performed the ovariectomy (OV and RAOV) or Sham (CTSham or RA) procedures at the same time, fifteen days before the rheumatoid arthritis induction. The RA and RAOV groups were immunized and then were injected with Met- BSA in the tibiotarsal joint. After 15 days of intra-articular injections the animals were euthanized. We evaluated the external manifestations of rheumatoid arthritis (perimeter joint) as well as animal weight, and food intake throughout the study. We also analyzed the cross-sectional areas (CSA) of gastrocnemius muscle fibers in 200 fibers (H&E method). In the gastrocnemius muscle, we analyzed mRNA expression by quantitative real time PCR followed by the Livak method (ΔΔCT). Results The rheumatoid arthritis induced reduction in CSA of gastrocnemius muscle fibers. The RAOV group showed a lower CSA of gastrocnemius muscle fibers compared to RA and CT-Sham groups. Skeletal muscle IGF-1 mRNA increased in arthritics and ovariectomized rats. The increased IGF-1 mRNA was higher in OV groups than in the RA and RAOV groups. Antrogin-1 mRNA also increased in the gastrocnemius muscle of arthritic and ovariectomized rats. However, the increased atrogin-1 mRNA was higher in RAOV groups than in the RA and OV groups. Gastrocnemius muscle MuRF-1 mRNA increased in the OVand RAOVgroups, but not in the RA and Shamgroups. However, the RAOV group showed higher MuRF-1 mRNA than the OV group. The myostatin gene expression was similar in all groups. Conclusion Loss of ovarian function results in increased loss of skeletal musclerelated ubiquitin ligases atrogin-1 and MuRF-1 in arthritic rats.

Objetivo Foram estudados os efeitos da perda da função ovariana (ovariectomia) sobre músculo esquelético e os níveis de RNAm de IGF-1, atrogina-1, MuRF-1, e de miostatina em modelo experimental de artrite reumatóide em ratos. Métodos 24 ratos Wistar (9 semanas, 195,3±17,4 gramas) foram distribuídos aleatoriamente em quatro grupos: controle (CT-Sham, n = 6); artrite reumatóide (RA, n = 6); ovariectomia sem artrite reumatóide (OV; n = 6); ovariectomia com artrite reumatóide (RAOV; n = 6). Os procedimentos da ovariectomia (OV e RAOV) ou simulação da ovariectomia (CT-Shamou RA) foramrealizados aomesmo tempo, quinze dias antes da indução da artrite reumatóide. Os grupos RA e RAOV foramimunizados e, em seguida, foram injetados com Met-BSA na articulação tibiotársica. Após 15 dias das injeções intra-articulares, os animais foram eutanasiados. Foram avaliadas as manifestações externas da artrite reumatóide (perimetria articular), bem como o peso dos animais e a ingestão de alimentos ao longo do estudo. Além disso, as áreas de secção transversa (CSA) do músculo gastrocnêmio foram analisadas em 200 fibras (método H & E). No músculo gastrocnêmio, a expressão de RNAm foi analisada por PCR quantitativo em tempo real, seguido pelo método Livak (ΔΔCT). Resultados A artrite reumatoide reduziu a CSA das fibras do músculo gastrocnêmio. O grupo RAOV mostrou uma CSA menor nas fibras do músculo gastrocnêmio em comparação com os grupos RA e CT-Sham. O RNAm do IGF-1 do músculo esquelético aumentou nos ratos artríticos e ovariectomizados. O RNAm do IGF-1 foi maior nos grupos OV do que nos grupos RA e RAOV. A expressão de antrogina-1 também aumentou no músculo gastrocnêmio dos ratos artríticos e ovariectomizados. No entanto, o aumento do RNAm da atrogina-1 foi maior no grupo RAOV do que nos grupos RA e OV. O RNAm da MuRF-1 aumentou nos grupos OV e RAOV, mas não nos grupos RA e CT-Sham. Porém, o grupo RAOV apresentou maior expressão gênica de MuRF-1 do que o grupo OV. A expressão do gene da miostatina foi semelhante em todos os grupos. Conclusão A perda de função ovariana resulta em perda de músculo esquelético associado às ubiquitina-ligases atrogina-1 e MuRF-1 em ratos artríticos.

Comparison of Classical and Secondary Cytologic Criteria Relative to Hybrid Capture for Diagnosing Cervical-vaginal Infection by Human Papillomavirus / Comparação entre os critérios citológicos clássicos e secundários para o diagnóstico de infecção cérvico-vaginal por papiloma vírus humano em relação à captura híbrida

Objective To compare the diagnostic accuracy of the classic Meisels cytologic criteria and the Schneider secondary criteria relative to the hybrid capture method for diagnosing HPV infection. Methods This was a retrospective study performed at a public university hospital. A total of 41 patients with a cytologic diagnosis of HPV infection and 40 HPV-negative patients were selected for review of the cervical-vaginal smears seeking to classical and secondary criteria. A single pathologist reviewed the slides in search of the criteria. The classical and secondary cytologic criteria were compared with the hybrid capture for diagnosing HPV infection. Bartleti test was applied for the age analysis, and Fisher's exact test was used to compare proportions. The tests were considered significant when the probability of rejecting the null hypothesis was less than 5% (p < 0.05). Results The Meisels criteria were less sensitive (34.0%) than the secondary Schneider criteria (57.5%) when compared with the hybrid capture (p < 0.0001), although the specificity of the former criteria was non-significantly higher (91.2% and 67.7%, respectively). In cases of moderate or intense inflammation, the sensitivity and specificity of the Schneider criteria were decreased, 33.3% and 50.0% respectively (p = 0.0115). Conclusions Compared with hybrid capture for diagnosis of HPV infection, the sensitivity of the secondary Schneider criteria was higher than the classical Meisels criteria.Moderate or intense inflammation reduces the sensitivity and specificity of the secondary Schneider criteria for diagnosing HPV infection using the hybrid capture as the gold standard.

Objetivo Comparar a acurácia diagnóstica dos critérios citológicos clássicos de Meisels com a dos critérios secundários de Schneider em relação a captura híbrida para o diagnóstico de infecção pelo HPV. Métodos Trata-se de estudo retrospectivo realizado em hospital público universitário. Quarenta e uma pacientes com diagnóstico citológico de infecção pelo HPV e 40 pacientes HPV-negativas foram selecionadas para avaliação dos esfregaços cervicaisvaginais em busca dos critérios clássicos e secundários. Um único patologista reviu as lâminas. Os critérios citológicos clássicos e secundários foram comparados com a captura híbrida para o diagnóstico de infecção pelo HPV. O teste de Bartleti foi aplicado para a análise das idades e o teste exato de Fisher para comparar proporções. Os testes foram considerados significativos quando a probabilidade de rejeitar a hipótese de nulidade foi menor que 5% (p < 0,05). Resultados Os critérios deMeisels forammenos sensíveis (34,0%) que os secundários de Schneider (57,5%) quando comparados com a captura híbrida (p < 0,0001), embora a especificidade dos critérios de Meisels não tenha sido significativamente superior (91,2% e 67,7%, respectivamente). Em casos de inflamação moderada ou intensa, a sensibilidade e especificidade dos critérios secundários de Schneider foram diminuídas, 33,3% e 50,0%, respectivamente (p = 0,0115). Conclusões Comparado a captura híbrida para o diagnóstico da infecção pelo HPV, a sensibilidade dos critérios secundários de Schneider foi maior que a dos critérios clássicos de Meisels. Inflamação moderada ou intensa reduziu a sensibilidade e especificidade dos critérios secundários de Schneider para o diagnóstico de infecção pelo HPV utilizando a captura híbrida como padrão-ouro.

Association of metabolic alterations with prognostic factors in malignant breast neoplasms. / Associação de alterações metabólicas com fatores prognósticos em neoplasias malignas de mama

Objectives: There are few studies in the literature correlating metabolic alterations with prognostic factors in breast cancer. The aims of this study were to evaluate serum levels of total cholesterol, HDL, LDL, triglycerides and fasting glucose, weight, body mass index and blood pressure, and relate them to prognostic factors (stage, lymph node involvement, histological grade, estrogen and progesterone receptors, ki-67 and Her2/neu) in patients with breast cancer. Methods: A retrospective study was conducted in Mastology Service of the Discipline of Gynecology and Obstetrics/Oncologycal Research Institute (IPON) of the Universidade Federal do Triângulo Mineiro (UFTM). We evaluated 100 patients with breast cancer treated at Mastology Clinic (surgical and/or clinical treatment). Serum levels of total cholesterol, HDL, LDL, triglycerides and fasting glucose, weight, body mass index, blood pressure, staging, lymph node involvement,histological grade and immunohistochemical panel (estrogen and progesterone receptors, ki-67 and HER-2/neu) were recorded. Data were expressed as the mean ± standard deviation, and the values were compared by using Student's t-test. P-values less than 0.05 were considered statisticallysignificant. Results: Histological grades 1 and 2 were significantly correlated with higher HDL serum levels (p=0.02). Higher levels of triglycerides were found more frequently in grade 3, and highest weight was related to Ki-67 positive, but only with a trend towards significance (p=0.07). Conclusion: HDL can be related to prognosis in breast cancer.

Objetivos: Há poucos estudos na literatura relacionando alterações metabólicas com fatores prognósticos em câncer de mama. Os objetivos desse estudo foram avaliar os níveis séricos de colesterol total, HDL, LDL, triglicérides e glicemia de jejum, peso, índice de massa corporal e pressão arterial, e relacioná-los com fatores prognósticos (estadiamento, envolvimento linfonodal, grau histológico, receptores de estrógeno e progesterona, ki-67 e Her2/neu) em pacientes com câncer de mama. Métodos: Um estudo retrospectivo foi realizado no Serviço de Mastologia da Disciplina de Ginecologia e Obstetrícia e Instituto de Pesquisa em Oncologia (IPON) da Universidade Federal do Triângulo Mineiro (UFTM). Nós avaliamos 100 pacientes com câncer de mama tratadas no Serviço de Mastologia (tratamento clínico e/ou cirúrgico). Níveis séricos de colesterol total, HDL, LDL, triglicérides e glicemia de jejum, peso, índice de massa corporal, pressão arterial, estadiamento, envolvimento linfonodal, grau histológico e painel imuno-histoquímico (receptores de estrógeno e progesterona, ki-67 e Her2/neu) foram registrados. Dados foram expressos em média ± desvio padrão, e os valores foram comparados utilizando-se o test t de Student. Valores de p menores que 0,05 foram considerados estatisticamente significativos. Resultados: Graus histológicos 1 e 2 foram relacionados significativamente com níveis séricos mais altos de HDL (p=0,02). Níveis mais elevados de triglicérides foram encontrados maisfrequentemente em tumores grau 3, e peso mais alto foi relacionado com positividade de Ki-67, mas apenas com tendência à significância (p=0,07). Conclusão: Níveis séricos de HDL podem estar relacionados ao prognóstico em neoplasia maligna de mama.

A retrospective study on cervical intraepithelial lesions of low-grade and undetermined significance: evolution, associated factors and cytohistological correlation / Estudo retrospectivo sobre lesões intraepiteliais cervicais de baixo grau e de significado indeterminado: evolução, fatores associados e correlação citohistológica

CONTEXT AND OBJECTIVES: Cervical cancer is an important cause of morbidity and mortality throughout the world. There is some controversy about the factors that may be associated with infection by the human papillomavirus (HPV) that may favor or protect against evolution from a low-grade intraepithelial lesion to a high-grade intraepithelial lesion or invasive neoplasia. The objective here was to evaluate the evolution of low-grade intraepithelial lesions and squamous or glandular lesions of undetermined significance, the associated factors and cytohistological correlations. DESIGN AND SETTING: Retrospective study conducted in a public tertiary-level university hospital. METHODS: Information was obtained by reviewing patient records and/or colposcopy reports. A statistical analysis was performed using logistic regression, calculating the odds ratio and applying chi-square tests. RESULTS: Of the 3390 patients, 409 evolved to high-grade intraepithelial lesions, of which 354 had an initial diagnosis of HPV infection, 27 of squamous atypia of undetermined significance, 22 of low-grade intraepithelial lesions with or without cytological diagnosis of infection by associated HPV and six of glandular cell atypia of undetermined significance. CONCLUSIONS: Lactobacillus sp and bacterial vaginosis on the smears, smoking and immunodepression were factors associated with evolution. A single partner, use of hormonal contraceptives, lower parity, age and a cytological diagnosis of cytolytic vaginosis, T. vaginalis, Candida sp or cocci were factors associated with protection. With regard to cytohistological correlation, there was a 74.08% agreement among patients with high-grade lesions and a biopsy obtained during the same period. .

CONTEXTO E OBJETIVOS: O câncer do colo uterino é importante causa de morbidade e mortalidade no mundo. Existem controvérsias sobre fatores que podem estar associados à infecção por papilomavírus humano (HPV) e favorecer ou proteger contra a evolução de lesão intraepitelial de baixo grau até lesão intraepitelial de alto grau ou neoplasia invasiva. O objetivo aqui foi de avaliar a evolução de lesões intraepiteliais de baixo grau e de significado indeterminado, escamosas ou glandulares, os fatores associados e as correlações citohistológicas. TIPO DE ESTUDO E LOCAL: Estudo retrospectivo realizado em hospital universitário público terciário. MÉTODOS: As informações foram obtidas por meio de revisão de prontuários e/ou fichas de colposcopia. A análise estatística foi realizada por meio de regressão logística, calculando-se o odds ratio e aplicando-se o teste qui-quadrado. RESULTADOS: Das 3.390 pacientes, 409 evoluíram para lesão intraepitelial de alto grau, das quais 354 tinham diagnóstico inicial de infecção por HPV, 27 de atipias escamosas de significado indeterminado, 22 de lesão intraepitelial de baixo grau com ou sem diagnóstico citológico de infecção por HPV associado e 6 de atipias em células glandulares de significado indeterminado. CONCLUSÕES: Lactobacillus sp e vaginose bacteriana nos esfregaços, tabagismo e imunodepressão foram fatores associados com a evolução. Único parceiro, uso de contraceptivo hormonal, baixa paridade, idade e diagnóstico citológico de vaginose citolítica, T. vaginalis, Candida sp ou cocos foram fatores associados a proteção. Com relação à correlação citohistológica, encontramos concordância de 74,08% ...

Human papillomavirus types 16 and 18 and the prognosis of patients with stage I cervical cancer

OBJECTIVE: This study sought to evaluate the prevalence of human papillomavirus (HPV) types 16 and 18 in women with clinical stage IB cervical cancer treated by radical hysterectomy with pelvic lymphadenectomy as well as to establish a correlation between HPV type and cancer prognosis. METHODS: A single-center cohort study was conducted with 86 patients who had undergone radical hysterectomy for stage I cervical cancer. Prognostic factors and the presence of HPV 16 and 18 were analyzed using a polymerase chain reaction assay. A univariate analysis using Kaplan-Meier curves was conducted to estimate survival. RESULTS: The prevalence of HPV 16 in the study group was 65.3%, and the prevalence of HPV 18 was 33.3%. The prevalence of infection with both viruses was 26.9%. Overall survival at 5 years was 91% among women with HPV 18 and 96% among those without this virus type (p = 0.133). Among the women with HPV 16, the overall survival was 94%, whereas this rate was 96% among those without this virus type (p = 0.663). Disease-free survival was unaffected by the presence of HPV type 16 or 18. CONCLUSION: In the present study, despite the high prevalence of HPV types 16 and 18, the presence of these virus types did not affect the prognosis of patients with stage I cervical cancer who underwent radical hysterectomy. .

Prevention of cervical cancer in women with ASCUS in the Brazilian Unified National Health System: cost-effectiveness of the molecular biology method for HPV detection / Prevenção de câncer de colo uterino em pacientes com ASCUS no Sistema Único de Saúde: custo-efetividade de método de biologia molecular para HPV

This study aimed to assess the performance of PCR as a means of detecting HPV 16/18 compared to the single probe-based PCR for detecting high-risk HPV, and evaluate these methods for detecting cervical intraepithelial neoplasia (CIN) in follow-ups for ASCUS testing. It also compares the costs of cytology, PCR methods, colposcopy and biopsy in the Brazilian Unified National Health System. Of the 81 patients with ASCUS, 41 (50.6%) tested positive for HPV 16/18 in PCR testing and 47 (58.02%) tested positive for high-risk HPV with single probe-based PCR testing. The negative predictive value was 93.75% for HPV 16/18 PCR and 100% for single probe-based PCR in cases that progressed to high-grade CIN. The annual costs of patient referral were the following: R$2,144.52 for referral of patients with ASCUS cytology for colposcopy; R$6,307.44 for referral of patients with ASCUS cytology and PCR positive for HPV 16/18 or colposcopy; R$3,691.80 for referral of patients with ASCUS cytology with single probe-based PCR positive for high-risk HPV. Therefore, cost per user can be reduced by performing single probe-based PCR for high-risk HPV on patients with ASCUS.

Os objetivos deste estudo foram avaliar o desempenho do PCR para detecção de HPV 16/18 versus PCR sonda única para a detecção de HPV de alto risco, avaliar estes métodos na detecção de neoplasia intraepitelial cervical (NIC) no seguimento de ASCUS, e comparar os custos de citologia, métodos de PCR, colposcopia e biópsia no Sistema Único de Saúde. Das 81 pacientes com ASCUS, 41 (50,6%) foram positivas para o HPV 16/18 PCR, e 47 (58,02%) foram positivas para PCR sonda única para HPV de alto risco. O valor preditivo negativo foi de 93,75% para HPV 16/18 PCR e 100% para PCR sonda única em casos que evoluíram para NIC de alto grau. Os custos anuais encaminhando todas as pacientes com ASCUS para a colposcopia, encaminhando à colposcopia as pacientes com ASCUS e PCR positivo para HPV 16/18 e encaminhando à colposcopia aquelas pacientes com ASCUS e PCR sonda única para HPV de alto risco positivo foram de R$2.144,52, R$6.307,44 e R$3.691,80, respectivamente. Considerando eventual redução dos custos para utilização em grandes quantidades, este método poderia ser realizado em ASCUS.

Macroscopic placental changes associated with fetal and maternal events in diabetes mellitus

OBJECTIVES: The current study sought to identify macroscopic placental changes associated with clinical conditions in women with or without diabetes and their newborns. METHODS: The study population consisted of 62 pregnant women clinically diagnosed with diabetes and 62 healthy women (control group). RESULTS: Among the subjects with diabetes, 43 women (69.3%) were diagnosed with gestational diabetes mellitus, 15 had diabetes mellitus I (24.2%), and four had diabetes mellitus II (6.5%). The mean age of the women studied was 28.5 ± 5.71 years, and the mean gestational age of the diabetic women was 38.51 weeks. Of the 62 placentas from diabetic pregnancies, 49 (79%) maternal surfaces and 59 (95.2%) fetal surfaces showed abnormalities, including calcium and fibrin deposits, placental infarction, hematoma, and fibrosis. A statistical association was found between newborn gender and fetal and maternal placental changes (p = 0.002). The mean weight of the newborns studied was 3,287 ± 563 g for women with diabetes mellitus, 3,205 ± 544 g for those with gestational diabetes mellitus, 3,563 ± 696 g forthose with diabetes mellitus II, and 3,095 ± 451 g forthose with diabetes mellitus I. CONCLUSIONS: Infarction, hematoma, calcification, and fibrin were found on the maternal and fetal placental surfaces in women with diabetes. Women with gestational diabetes and post-term infants had more calcium deposits on the maternal placental surface as compared to those with type I and type II diabetes.