RESUMEN
OBJECTIVE: To evaluate cytokine levels of interleukin (IL)-1ß, IL-4, IL-6, IL-17a, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ in the gingival crevicular fluid (GCF) of periodontal sites in individuals with Down syndrome (DS) and analyze their relationship with clinical periodontal parameters. MATERIALS AND METHODS: A cross-sectional study was conducted with 49 DS patients and 32 individuals without DS (non-DS group). Periodontal probing depth (PPD), clinical attachment level (CAL), bleeding on probing (BoP), and visible plaque index (VPI) were evaluated. The periodontal sites were classified as shallow, moderate, and deep. GCF was collected in all shallow sites and, when present, in moderate and deep sites for the analysis of cytokine levels. The cytokines, IL-1ß, IL-4, IL-6, IL-17a, TNF-α, and IFN-γ, were quantified using the Luminex® automatic analyzer system. RESULTS: The DS group presented greater severity of periodontitis compared to the non-DS group (P = 0.005). The DS group showed a significant direct correlation of IL-1ß and an inverse correlation of IFN-γ and IL-14 with all periodontal variables. In the analysis stratified by periodontal pocket depth, we observed a higher level of IFN-γ, IL-17a, IL-1ß, and IL-6 in the shallow sites, and IL-17a, IL-1ß, and IL-6 in deep pockets of DS group individuals. Multivariate models showed that higher levels of IL-1ß, IL-4, IL-6, and IL-17a were associated with Down syndrome even after adjusting for periodontal status, sex, and age. CONCLUSION: The findings suggest that people with DS have greater periodontal impairment and higher levels of cytokines in GCF, even in sites having clinical periodontal parameters similar to those of individuals without DS. These data reiterate the concept of an altered and less effective immune response in the population with DS in the face of a periodontal microbial challenge. CLINICAL RELEVANCE: Elevated periodontal inflammation burden can be observed with higher cytokine levels in the gingival crevicular fluid of people with Down syndrome, especially IL-1, IL-4, IL-6, and IL-17, regardless of the stage of periodontitis.
Asunto(s)
Citocinas , Síndrome de Down , Líquido del Surco Gingival , Índice Periodontal , Humanos , Líquido del Surco Gingival/química , Estudios Transversales , Masculino , Femenino , Síndrome de Down/metabolismo , Citocinas/metabolismo , Citocinas/análisis , Adulto , Índice de Placa Dental , AdolescenteRESUMEN
Euterpe oleracea (açaí) fruit has approximately 15% pulp, which is partly edible and commercialized, and 85% seeds. Although açaí seeds are rich in catechins-polyphenolic compounds with antioxidant, anti-inflammatory, and antitumor effects-almost 935,000 tons/year of seeds are discarded as industrial waste. This work evaluated the antitumor properties of E. oleracea in vitro and in vivo in a solid Ehrlich tumor in mice. The seed extract presented 86.26 ± 0.189 mg of catechin/g of extract. The palm and pulp extracts did not exhibit in vitro antitumor activity, while the fruit and seed extracts showed cytotoxic effects on the LNCaP prostate cancer cell line, inducing mitochondrial and nuclear alterations. Oral treatments were performed daily at 100, 200, and 400 mg/kg of E. oleracea seed extract. The tumor development and histology were evaluated, along with immunological and toxicological parameters. Treatment at 400 mg/kg reduced the tumor size, nuclear pleomorphism, and mitosis figures, increasing tumor necrosis. Treated groups showed cellularity of lymphoid organs comparable to the untreated group, suggesting less infiltration in the lymph node and spleen and preservation of the bone marrow. The highest doses reduced IL-6 and induced IFN-γ, suggesting antitumor and immunomodulatory effects. Thus, açaí seeds can be an important source of compounds with antitumor and immunoprotective properties.
RESUMEN
Euterpe oleracea Mart. (açai) is a native palm from the Amazon region. There are various chemical constituents of açai with bioactive properties. This study aimed to evaluate the chemical composition and cytotoxic effects of açai seed extract on breast cancer cell line (MCF-7). Global Natural Products Social Molecular Networking (GNPS) was applied to identify chemical compounds present in açai seed extract. LC-MS/MS and molecular networking were employed to detect the phenolic compounds of açai. The antioxidant activity of açai seed extract was measured by DPPH assay. MCF-7 breast cancer cell line viability was evaluated by MTT assay. Cell death was evaluated by flow cytometry and time-lapse microscopy. Autophagy was evaluated by orange acridin immunofluorescence assay. Reactive oxygen species (ROS) production was evaluated by DAF assay. From the molecular networking, fifteen compounds were identified, mainly phenolic compounds. The açai seed extract showed cytotoxic effects against MCF-7, induced morphologic changes in the cell line by autophagy and increased the ROS production pathway. The present study suggests that açai seed extract has a high cytotoxic capacity and may induce autophagy by increasing ROS production in breast cancer. Apart from its antioxidant activity, flavonoids with high radical scavenging activity present in açai also generated NO (nitric oxide), contributing to its cytotoxic effect and autophagy induction.
Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Muerte Celular/efectos de los fármacos , Euterpe/química , Extractos Vegetales/farmacología , Especies Reactivas de Oxígeno/metabolismo , Semillas/química , Antioxidantes/química , Antioxidantes/farmacología , Autofagia/efectos de los fármacos , Línea Celular Tumoral , Cromatografía Liquida/métodos , Femenino , Flavonoides/química , Flavonoides/farmacología , Frutas/química , Humanos , Células MCF-7 , Fenoles/química , Fenoles/farmacología , Extractos Vegetales/química , Polifenoles/química , Polifenoles/farmacología , Espectrometría de Masas en Tándem/métodosRESUMEN
In the present study, novel, 1,3-diaryltriazene-derived triazene compounds were synthesized and tested. Triazenes are versatile and belong to a group of alkylating agents with interesting physicochemical properties and proven biological activities. This study describes the synthesis, molecular and crystalline structure, biological activity evaluation, and antifungal and antimicrobial potentials of 1,3-bis(X-methoxy-Y-nitrophenyl)triazenes [X = 2 and 5; Y = 4 and 5]. The antimicrobial and antifungal activities of the compounds were tested by evaluating the sensitivity of bacteria (American Type Culture Collection, ATCC) and clinical isolates to their solutions using standardized microbiological assays, cytotoxicity evaluation, and ecotoxicity tests. The antimicrobial potentials of triazenes were determined according to their minimum inhibitory concentrations (MICs); these compounds were active against gram-positive and gram-negative bacteria, with low MIC values. The most surprising result was obtained for T3 having the effective MIC of 9.937 µg/mL and antifungal activity against Candida albicans ATCC 90028, C. parapsilosis ATCC 22019, and C. tropicallis IC. To the best of our knowledge, this study is the first to report promising activities of triazene compounds against yeast and filamentous fungi. The results showed the potential utility of triazenes as agents affecting selected resistant bacterial and fungal strains.
Asunto(s)
Triazenos/química , Triazenos/farmacología , Antiinfecciosos/química , Antiinfecciosos/farmacología , Antineoplásicos/química , Antineoplásicos/farmacología , Relación Dosis-Respuesta a Droga , Pruebas de Sensibilidad Microbiana , Modelos Moleculares , Estructura Molecular , Relación Estructura-ActividadRESUMEN
BACKGROUND: This study addresses the antitumoral properties of Penicillium purpurogenum isolated from a polluted lagoon in Northeastern Brazil. METHODS: Ethyl Acetate Extracellular Extract (EAE) was used. The metabolites were studied using direct infusion mass spectrometry. The solid Ehrlich tumor model was used for antitumor activity. Female Swiss mice were divided into groups (n = 10/group) as follows: The negative control (CTL-), treated with a phosphate buffered solution; the positive control (CTL+), treated with cyclophosphamide (25 mg/kg); extract treatments at doses of 4, 20, and 100 mg/kg; animals without tumors or treatments (Sham); and animals without tumors treated with an intermediate dose (EAE20). All treatments were performed intraperitoneally, daily, for 15 days. Subsequently, the animals were euthanized, and the tumor, lymphoid organs, and serum were used for immunological, histological, and biochemical parameter evaluations. RESULTS: The extract was rich in meroterpenoids. All doses significantly reduced tumor size, and the 20 and 100 mg/kg doses reduced tumor-associated inflammation and tumor necrosis. The extract also reduced the cellular infiltration of lymphoid organs and circulating TNF-α levels. The extract did not induce weight loss or renal and hepatic toxic changes. CONCLUSIONS: These results indicate that P. purpurogenum exhibits immunomodulatory and antitumor properties in vivo. Thus, fungal fermentation is a valid biotechnological approach to the production of antitumor agents.
Asunto(s)
Antineoplásicos/farmacología , Carcinoma de Ehrlich/tratamiento farmacológico , Citocinas/metabolismo , Mediadores de Inflamación/metabolismo , Talaromyces/metabolismo , Animales , Antineoplásicos/aislamiento & purificación , Antineoplásicos/toxicidad , Carcinoma de Ehrlich/inmunología , Carcinoma de Ehrlich/metabolismo , Carcinoma de Ehrlich/patología , Femenino , Ratones , Estructura Molecular , Carga Tumoral/efectos de los fármacos , Microbiología del AguaRESUMEN
Dendritic cells (DCs) are the most efficient antigen-presenting cells and link the innate immune sensing of the environment to the initiation of adaptive immune responses, which may be directed to either acceptance or elimination of the recognized antigen. In cancer patients, though DCs would be expected to present tumor antigens to T lymphocytes and induce tumor-eliminating responses, this is frequently not the case. The complex tumor microenvironment subverts the immune response, blocks some effector mechanisms, and drives others to support tumor growth. Chronic inflammation in a tumor microenvironment is believed to contribute to the induction of such regulatory/tolerogenic response. Among the various mediators of the modulatory switch in chronic inflammation is the "antidanger signal" chaperone, heat shock protein 27 (Hsp27), that has been described, interestingly, to be associated with cell migration and drug resistance of breast cancer cells. Thus, here, we investigated the expression of Hsp27 during the differentiation of monocyte-derived DCs (Mo-DCs) from healthy donors and breast cancer patients and evaluated their surface phenotype, cytokine secretion pattern, and lymphostimulatory activity. Surface phenotype and lymphocyte proliferation were evaluated by flow cytometry, interferon- (IFN-) γ, and interleukin- (IL-) 10 secretion, by ELISA and Hsp27 expression, by quantitative polymerase chain reaction (qPCR). Mo-DCs from cancer patients presented decreased expression of DC maturation markers, decreased ability to induce allogeneic lymphocyte proliferation, and increased IL-10 secretion. In coculture with breast cancer cell lines, healthy donors' Mo-DCs showed phenotype changes similar to those found in patients' cells. Interestingly, patients' monocytes expressed less GM-CSF and IL-4 receptors than healthy donors' monocytes and Hsp27 expression was significantly higher in patients' Mo-DCs (and in tumor samples). Both phenomena could contribute to the phenotypic bias of breast cancer patients' Mo-DCs and might prove potential targets for the development of new immunotherapeutic approaches for breast cancer.
Asunto(s)
Neoplasias de la Mama/metabolismo , Células Dendríticas/metabolismo , Proteínas de Choque Térmico HSP27/metabolismo , Monocitos/metabolismo , Línea Celular Tumoral , Ensayo de Inmunoadsorción Enzimática , Femenino , Citometría de Flujo , Humanos , Interferón gamma/metabolismo , Interleucina-10/metabolismo , Reacción en Cadena de la PolimerasaRESUMEN
Pain is recognized as one of the main symptoms in knee osteoarthritis and is the main reason why patients seek medical attention. Scoparia dulcis has been popularly used to relieve discomfort caused by various painful conditions. The objective of the study is to evaluate the analgesic and anti-inflammatory effect of the crude extract of S. dulcis, in an experimental model of osteoarthritis. The experiment was performed with Wistar rats divided into 4 groups with 5 animals each: healthy, saline, crude extract, and meloxicam groups. Knee osteoarthritis was induced by intra-articular injection of sodium mono-iodoacetate. First, clinical parameters of pain were assessed at days 0, 5, 10, 15, and 20 after induction. Second, the potential cyclooxygenase inhibition was evaluated, and the cytokines of the synovial fluid were quantified. An in silico test and Molecular Docking tests were performed. A histopathological evaluation was made on articular cartilage with safranin O staining. The results showed that a 15-day treatment with crude extract reduced edema, spontaneous pain, peripheral nociceptive activity, and proinflammatory cytokines in the synovial fluid. The highest inhibition of cyclooxygenase 2 in the crude extract occurred at 50 µg/mL. The crude extract of S. dulcis presents therapeutic potential for the treatment of osteoarthritis due to its anti-inflammatory and anti-nociceptive action.
Asunto(s)
Osteoartritis de la Rodilla/tratamiento farmacológico , Osteoartritis de la Rodilla/patología , Extractos Vegetales/farmacología , Scoparia/química , Animales , Biomarcadores , Cartílago Articular/efectos de los fármacos , Cartílago Articular/patología , Cromatografía Líquida de Alta Presión , Citocinas/metabolismo , Ratones , Osteoartritis de la Rodilla/etiología , Osteoartritis de la Rodilla/metabolismo , Extractos Vegetales/química , Prostaglandina-Endoperóxido Sintasas/genética , Prostaglandina-Endoperóxido Sintasas/metabolismo , Ratas , Espectrometría de Masa por Ionización de ElectrosprayRESUMEN
BACKGROUND: Currently known risk factors explain only a small fraction of preterm birth (PTB). Previous PTB is one of the most important predictors. However, this information is not available in primiparous women. Few studies have looked at associations between regulatory cytokine expression (RCE) and PTB and the results are conflicting. OBJECTIVE: To investigate the association of RCE-Interleukin 10 (IL-10) and Transforming Growth Factor ß (TGF-ß)-with PTB, and to assess whether bacterial vaginosis (BV) is involved in this relationship. METHODS: This was a case-control study nested in a prospective cohort-called BRISA. Women with singleton pregnancies were interviewed from 22 to 25 weeks of gestational age (GA). Women were recruited from health services in São Luís, Brazil. A blood sample was collected and gynecological examination was performed. Serum IL-10 and TGF-ß were determined using cytometric bead array. Nugent score >7 and/or the presence of clue cells were used for BV diagnosis. All PTB estimated by ultrasound dating performed before 20 weeks of gestational age were considered cases. Controls were selected by simple random sampling from the rest of the cohort, at a 2:1 ratio. Different models were tested, according to the main independent variable. Odds ratios (OR) and 95% confidence intervals (95%CI) were estimated by regression analyses. RESULTS: The study included 327 pregnant women, 109 cases and 218 controls. No associations were found between BV and PTB (P = 1.44; 95%CI: 0.51-3.77). Low levels of IL-10 (OR = 2.92 95%CI: 1.38-6.16) or TGF-ß (OR = 16.90 95%CI: 6.42-44.51) or both simultaneously (OR = 77.16 95%CI: 7.99-744.88) were associated with increasing odds of PTB, even after adjustment for confounding. CONCLUSION: Decreased RCE is a risk factor for PTB. This relationship, however, is not triggered by the presence of BV. Low IL-10/TGF-ß levels from 22 to 25 weeks of GA could be used as early predictors of PTB. We suggest monitoring of these RCE, especially among primiparous women, for whom history of previous PTB is not available.
Asunto(s)
Interleucina-10/metabolismo , Complicaciones Infecciosas del Embarazo/epidemiología , Nacimiento Prematuro/epidemiología , Factor de Crecimiento Transformador beta/metabolismo , Vaginosis Bacteriana/epidemiología , Adulto , Brasil/epidemiología , Estudios de Casos y Controles , Femenino , Humanos , Oportunidad Relativa , Embarazo , Segundo Trimestre del Embarazo , Nacimiento Prematuro/inmunología , Estudios Prospectivos , Factores de Riesgo , Adulto JovenRESUMEN
Contexto: A inclusão da mulher no mercado de trabalho é fato, entretanto, aspectos fisiológicos relacionados ao gênero ainda são vistos pelos empregadores como um aspecto negativo, dentre eles, a gravidez. Nesse sentido, pouco se sabe sobre fatores relacionados à gestação como causa de absentismo e se essas condições realmente constituem um fator que reduz a produtividade de uma mulher trabalhadora. Objetivo: Avaliar as principais causas de afastamento do trabalho por pacientes gestantes atendidas no ambulatório especializado de Obstetrícia da Maternidade Marly Sarney e relacionar com as características socioeconômicas e culturais. Método: Neste estudo descritivo qualitativo, os dados foram coletados no período de março a junho de 2013. Por meio de um questionário estruturado em entrevista, aplicado durante as consultas, foi realizado um levantamento dos dados socioeconômicos e culturais das pacientes atendidas no pré-natal, relacionando causas de absentismo na atividade profissional. Os dados obtidos foram tabulados e utilizados para estudos de frequência e associação pelo teste do ?2 ou exato de Fisher. Resultados: A maioria das trabalhadoras gestantes entrevistadas apresentaram idade entre 25 e 35 anos (62%), com ensino médio completo (70%), casadas ou com união estável (63%), no terceiro trimestre de gestação (49%) e com renda familiar entre 1 e 2 salários mínimos (41%). As trabalhadoras que possuem vínculo empregatício apresentam associação com maior grau de escolaridade e renda, enquanto que as trabalhadoras domésticas tiveram associação com menor escolaridade e renda. As gestantes economicamente ativas que relataram maior absentismo tiveram uma distribuição proporcionalmente maior nas trabalhadoras de maior renda. Conclusão: Os sintomas relacionados à gravidez são fatores que indubitavelmente levam ao absentismo. Contudo, o presente estudo levanta dados inéditos e relevantes sobre o perfil e comportamento das mulheres em atividade laboral, no contexto da gestação, ilustrando que a qualificação profissional influencia diretamente no comportamento da gestante. Assim, a atenção ao perfil dessas mulheres durante o atendimento pode ser importante para melhorar a efetividade do acompanhamento pré-natal das pacientes gestantes e trabalhadoras.
Context: The inclusion of women in the labor market is a fact, however, physiological aspects related to gender are still viewed by employers as a negative aspect, among them, pregnancy. Accordingly, little is known about factors related to pregnancy as a cause of absenteeism and whether these conditions actually constitute a factor that reduces the productivity of a working woman. Objective: To evaluate the main causes of sick leave for pregnant patients seen in the outpatient clinic of Obstetrics Maternity Marly Sarney and to relate them to socio-economic and cultural characteristics. Method: In this qualitative descriptive study, the data were collected from March to June 2013. Through a structured interview questionnaire administered during the consultations, a survey of socio-cultural data from patients treated prenatally was performed by relating the causes of absenteeism. Data were tabulated and used for studies of frequency and association by ?2 or Fisher's exact tests. Results: The majority of the working women interviewed were aged between 25 and 35 years (62%), had completed high school (70%), were married or in a stable relationship (63%), were in the third trimester of pregnancy (49%), and with family income between 1 and 2 minimum wages (41%). Workers who have employment are associated with higher levels of education and income, while domestic workers were associated with lower education and income. Economically active women who reported higher absenteeism had a proportionally greater distribution in higher-income workers. Conclusion: Related pregnancy symptoms are factors that undoubtedly lead to absenteeism. However, this study raises novel and relevant information about the profile and behavior of women in labor activity, in the context of pregnancy, illustrating that the qualification directly influences the behavior of pregnant women. Thus, attention to the profile of these women during the service may be important to improve the effectiveness of prenatal care of pregnant patients and workers.
Asunto(s)
Humanos , Femenino , Embarazo , Salud Laboral , Ausencia por Enfermedad , Mujeres Embarazadas/psicología , AbsentismoRESUMEN
Mechanisms involved in severe P. vivax malaria remain unclear. Parasite polymorphisms, parasite load and host cytokine profile may influence the course of infection. In this study, we investigated the influence of circumsporozoite protein (CSP) polymorphisms on parasite load and cytokine profile in patients with vivax malaria. A cross-sectional study was carried out in three cities: São Luís, Cedral and Buriticupu, Maranhão state, Brazil, areas of high prevalence of P. vivax. Interleukin (IL)-2, IL-4, IL-10, IL-6, IL-17, tumor necrosis factor alpha (TNF-α, interferon gamma (IFN-γ and transforming growth factor beta (TGF-ß were quantified in blood plasma of patients and in supernatants from peripheral blood mononuclear cell (PBMC) cultures. Furthermore, the levels of cytokines and parasite load were correlated with VK210, VK247 and P. vivax-like CSP variants. Patients infected with P. vivax showed increased IL-10 and IL-6 levels, which correlated with the parasite load, however, in multiple comparisons, only IL-10 kept this association. A regulatory cytokine profile prevailed in plasma, while an inflammatory profile prevailed in PBMC culture supernatants and these patterns were related to CSP polymorphisms. VK247 infected patients showed higher parasitaemia and IL-6 concentrations, which were not associated to IL-10 anti-inflammatory effect. By contrast, in VK210 patients, these two cytokines showed a strong positive correlation and the parasite load was lower. Patients with the VK210 variant showed a regulatory cytokine profile in plasma, while those infected with the VK247 variant have a predominantly inflammatory cytokine profile and higher parasite loads, which altogether may result in more complications in infection. In conclusion, we propose that CSP polymorphisms is associated to the increase of non-regulated inflammatory immune responses, which in turn may be associated with the outcome of infection.
Asunto(s)
Citocinas/sangre , Variación Genética , Malaria Vivax/epidemiología , Malaria Vivax/patología , Carga de Parásitos , Plasmodium vivax/genética , Proteínas Protozoarias/genética , Adolescente , Adulto , Animales , Brasil/epidemiología , Células Cultivadas , Niño , Preescolar , Ciudades/epidemiología , Estudios Transversales , Femenino , Humanos , Leucocitos Mononucleares/inmunología , Malaria Vivax/parasitología , Masculino , Persona de Mediana Edad , Plasmodium vivax/aislamiento & purificación , Adulto JovenRESUMEN
O estudo da anatomia macroscopica das artérias coronarias e de grande importância para a cirurgia cardiaca uma vez que as variaçöes anatomicas säo abundantes e algumas repercussoes dessas variaçöes ainda säo desconhecidas. Nosso objetivo é comparar o padräo de distribuiçäo coronariana quanto a dominância entre coraçöes de indivíduos normais (grupos de pecas anatomicas) e indivíduos com doença coronariana (paciente com indicaçäo de revascularizacao do miocardio). Foi estudado o padrao de circulaçäo coronariana de dois grupos: o grupo I constituido por 119 pecas anatomicas obtidas de individuos cuja causa mortis nao tinha sido doença cardiovascular e o grupo II constituido de 150 filmes de cateterismo obtidos de pacientes com doença coronariana e com indicaçäo de revascularizaçäo do miocardio. No primeiro grupo as arterias coronarias foram dissecadas apos fixaçäo em formalina a 10 por cento. No segundo, os filmes foram analisados cuidadosamente...