Production of Nitric Oxide and Expression of Inducible Nitric Oxide Synthase in Ovarian Cystic Tumors

Tumor sections from nonneoplastic (n = 15), benign (n = 28), and malignant ovarian tumors (n = 20) were obtained from 63 women. Immunohistochemistry of the tumor sections demonstrated that inducible nitric oxide synthase (iNOS) expression was increased in ovarian cancer samples compared to nonneoplastic or benign tumor samples. Using the Griess method, nitric oxide (NO) metabolite levels were also found to be elevated in malignant tumor samples compared to benign tumor samples (P < .05). For stage I ovarian cancer, intracystic NO levels >80 μM were more frequent than NO levels <80 μM, and iNOS expression in well-differentiated carcinomas was greater than in moderately/poorly differentiated carcinomas (P < .05). These data suggest an important role for NO in ovarian carcinogenesis

Circulating Cytokines and Nitric Oxide are Involved in the Inhibition of Neutrophil Migration in Patients with Uterine Cervical Neoplasia

Aim To verify if patients with cervical neoplasia produce mediators that reduce leukocyte function. Methods Control neutrophils incubated with normal serum or serum from pre-invasive or invasive neoplasia patients were assayed for chemotaxis. Mediators were assayed in serum and in leukocyte supernatants. Experiments were also performed in random patients after surgery. Results Neutrophils incubated with patient sera, but not normal sera, failed to migrate towards the chemoattractants. In invasive neoplasia compared to controls, IL-6 and IL-8, and IL-10 and TNF-α were elevated in serum and in neutrophil supernatants, respectively. Nitrite levels were elevated in mononuclear cell supernatants from patients than controls. After surgery, serum cytokine levels were reduced, mainly in pre-invasive patients. Neutrophils treated with serum from pre-invasive patients undergone surgery had restored migration. Conclusion Patients with cervical neoplasia produce mediators, predominantly induced by tumor cells, able to impair the inflammatory response at very early stages of disease

Caracterização de marcadores inflamatórios associados a pacientes com lúpus eritematoso sistêmico em tratamento

ResumoObjetivoCaracterizar os perfis inflamatórios de pacientes com lúpus eritematoso sistêmico (LES) que recebiam o tratamento padrão em comparação com controles saudáveis.Pacientes e métodosColetou‐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.ResultadosOs 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.ConclusãoOs 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.AbstractObjectiveTo characterize the inflammatory profiles of patients with systemic lupus erythematosus (SLE) receiving standard treatment compared to healthy controls.Patients and methodsPeripheral venous blood was collected from SLE patients (n = 14) and controls (n = 18) at enrollment. Blood samples were used for quantification, by flow cytometry, of CD11b (integrin) and 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.ResultsPatients had a median (interquartile range) SLEDAI score of 1.0 (0 ‐ 2.0) characteristic of patients in remission. IL‐6 and IL‐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 IL‐2, IL‐5, IL‐8 and TNF‐ α did not significantly differ between patients and controls. Flow cytometric analysis revealed that the CD11b expression levels were reduced in lymphocytes (but not in neutrophils) obtained from SLE patients, while surface expression of the chemokine receptor CXCR2 was similar in both neutrophils and lymphocytes.ConclusionSLE patients receiving standard treatment presented with elevated systemic levels of IL‐6 and IL‐10, reduced neutrophil phagocytic capacity, and reduced lymphocyte expression of CD11b even when symptoms were in remission. These alterations to innate immune components may put these individuals at a greater risk for acquiring infections

Planejamento familiar e o impacto da laqueadura na taxa de natalidade no Brasil: uma revisão sistemática : Family planning and the impact of tubal sterilization in Brazil: a systematic review

Ao se buscar compreender o desenvolvimento social brasileiro, uma variável a ser considerada são os níveis de natalidade da nossa população e os métodos de organização e planejamento das famílias brasileiras, desta maneira este tem como objetivo fazer uma análise sistemática da relação entre as taxas de natalidade e o desenvolvimento de intervenções como a laqueadura, para tal este se embasou no método de pesquisa qualitativo com ênfase no levantamento bibliográfico. Concluindo que há uma relação muito íntima entre os métodos de contracepção e a queda de natalidade média brasileira

The relationship of host immune cells, cytokine and nitric oxide production to tumor cells in ovarian carcinoma

AIMS: This brief review focuses on the current understanding of the complex relationship of tumor-associated mononuclear cells (TAMs) with neoplastic cells, summarizing their immunological efficiency, cytokine profile and production of nitric oxide (NO) in the tumor microenvironment, with current insights on how this might affect tumor growth. DATA SOURCE: Data was obtained through Medline from articles indexed during the last 10 years. The main key words used in the research were: cancer, ovarian cancer, cytokine, nitric oxide (NO), mononuclear cell, lymphocyte, macrophage. SELECTION OF STUDIES AND DATA COLLECTION: 30 studies were reviewed, which contained data regarding the production of cytokines and NO by TAMs or malignant cells, and tried to establish a correlation between these mediators and tumor growth, especially in ovarian carcinoma. DATA SUMMARY: TAMs consist mainly of macrophages and T lymphocytes which present lower proliferative indices and cytotoxicity compared to autologous blood monocytes, although they are able to release various cytokines. The profile of cytokine expression could help to explain both the immunological impairment observed in patients with advanced carcinoma diseases and the potential of TAMs to exert antitumor activity, which makes these cells an attractive target for therapeutic intervention. NO is also produced in the tumor microenvironment. Several reports in animals suggest a tumoricidal role for NO, but in human tumors its role has not been well-established and may change during tumor progression

Failure of neutrophil migration toward infectious focus in severe sepsis: a critical event for the outcome of this syndrome

Sepsis is a systemic inflammatory response commonly caused by bacterial infection. We demonstrated that the outcome of sepsis induced by cecal ligation and puncture (CLP) correlates with the severity of the neutrophil migration failure towards infectious focus. Failure appears to be due to a decrease in the rolling and adhesion of neutrophil to endothelium cells. It seems that neutrophil migration impairment is mediated by the circulating inflammatory cytokines, such as TNF-α and IL-8, which induce the nitric oxide (NO) production systemically. It is supported by the fact that intravenous administration of these cytokines reduces the neutrophil migration induced by different inflammatory stimuli, and in severe sepsis the circulating concentrations of the cytokines and chemokines are significantly increased. Moreover, the neutrophil migration failure and the reduction in the rolling/adhesion were not observed in iNOS-/- mice and, aminoguanidine prevented this event. We also demonstrated that the failure of neutrophil migration is a Toll-4 receptor (TLR4) dependent mechanism, since it was not observed in TLR4 deficient mice. Furthermore, it was also observed that circulating neutrophils obtained from septic patients present failure of neutrophil chemotaxis toward fMLP, IL-8, and LTB4 and an increased in sera concentrations of NO3 and cytokines. In conclusion, we demonstrated that, in sepsis, failure of neutrophil migration is critical for the outcome and that NO is involved in the process

Effect of myocardial protection and perfusion temperature on production of cytokines and nitric oxide during cardiopulmonary bypass Efeito da proteção miocárdica e temperatura de perfusão sobre a produção de citocinas e óxido nítrico durante bypass cardiopulmonar

PURPOSE: To investigate the effects of different conditions used during cardiopulmonary bypass (CPB) surgery on accompanying production of cytokine and nitric oxide (NO). METHODS: Patients undergoing CPB for the first time were prospectively enrolled and divided into two groups according to CPB parameters performed: i) normothermia (36.5-37&deg;C) with blood cardioplegia (NB group, n=10) and ii) hypothermia (29-31&deg;C) with crystalloid cardioplegia (HC group, n=10). Plasma samples obtained following intubation (baseline), during (5 and 30 min) and after (4 and 24 h) CPB were assayed for cytokines (ELISA) and NO metabolites (Griess reaction). RESULTS: Peak concentrations of interleukin (IL)-6 and IL-8 were reached at 4 h post CPB in both groups, but in the HC group those levels increased earlier and persisted for longer (24 h) compared to baseline (P < 0.05). IL-10 levels also increased at 4 h compared to baseline, but only significantly so in the HC group. NO metabolites were reduced in HC group at all time points compared to baseline (P < 0.05), while no significant differences were detected in the NB group. CONCLUSION: The association between increased systemic levels of cytokines and reduced NO production in the HC group suggests that different myocardial protection and/or perfusion temperature used during CPB may contribute to the extent of inflammatory response.<br>OBJETIVO: Investigar a hipótese de que diferentes procedimentos durante o bypass cardiopulmonary (BCP) causa diferentes níveis de citocinas (IL) e óxido nítrico (NO). MÉTODOS: Pacientes submetidas a BCP foram prospectivamente estudadas de acordo com bypass realizado sobre normotermia (36.5-37&deg;C) com cardioplegia sanguínea (NB group, n=10) or hipotermia (29-31&deg;C) com cardioplegia cristalóide (HC group, n=10). Amostras de Plasma foram obtidas após a intubação (linha de base), durante (5, 30 min) e após (4, 24 h) o BCP. Os ensaios foram realizados através de ELISA (IL) e metabólitos do NO (reação de Griess). RESULTADOS: Os picos de concentrações de IL-6 and IL-8 estavam aumentados em 4 h pós BCP em ambos os grupos, mas no grupo HC estes níveis aumentaram precocemente e persistiram aumentadas por 24 h, comparado a linha de base (P<0.05). O nível de IL-10 também teve o pico em 4 h, mas estatisticamente significante somente no grupo HC, comparado a linha de base. Os metabólitos do NO estavam reduzidos no grupo HC, em todo o tempo, comparado a linha de base (P<0.05), enquanto nenhuma diferença estatisticamente significante foi detectada no grupo NB. CONCLUSÃO: A associação entre o aumento sistêmico dos níveis de citocina e a redução da produção de NO no grupo HC sugere que o tipo de proteção miocárdica e/ou temperatura de perfusão no BCP pode ser um fator determinante na extensão da resposta inflamatória