Introdução: Os mecanismos moleculares envolvidos na fisiopatologia dos Transtornos de Humor ainda não estão completamente elucidados. Nos últimos anos tem-se verificado um crescente reconhecimento de que alterações no sistema imune, no estresse oxidativo e de fatores neurotróficos poderiam contribuir para o desenvolvimento dos episódios de humor. O diagnóstico de Transtorno de Humor Bipolar é um desafio a ser reconhecido devido ao elevado grau de sobreposição de sintomas, que são apresentados por um paciente bipolar durante o episódio depressivo e se correlacionam com os critérios de diagnóstico para depressão maior. Neste contexto, a busca por marcadores periféricos para transtornos psiquiátricos segue há muitos anos, contudo permanece indefinida. Objetivos: Em vista disso, neste estudo avaliamos diferentes marcadores periféricos em pacientes com Depressão Unipolar e Depressão Bipolar, visando à busca de possíveis diferenças entre estes dois transtornos do humor. Métodos: Para este fim, medimos os níveis séricos de BDNF, IL-2, IL- 4, IL-6, IL-10, TNF, IFN-P, IL-17, danos a lipídios e proteínas em 54 pacientes ambulatoriais com depressão Bipolar e Unipolar pareados a 54 voluntários saudáveis. Episódio depressivo foi avaliado através da Escala Hamilton de Depressão (HAM-D). Resultados: Neste estudo encontramos aumento da IL-6 em ambos os grupos estudados comparados ao controles (p = 0,020 e p = 0, 001, respectivamente), bem como o aumento do dano a proteínas em pacientes unipolares (p = 0,003). Não foram observadas alterações nos níveis de BDNF em ambos os grupos de pacientes (p =0,295) e no conteúdo de peroxidação de lipídios (p = 0,860). Uma correlação positiva foi encontrada entre os valores de HAM-D e níveis de carbonilação (r =0,291; p =0,036) em pacientes bipolares. Conclusão: Nossos resultados indicam o envolvimento do estresse oxidativo e de uma alteração no sistema imune inflamatório em pacientes depressivos, contudo os marcadores aqui estudados não seriam ideais para diferenciação dos transtornos depressivos bipolares e unipolares, sendo necessários mais estudos, com uma amostra maior, para validação destes achados. / Background: The molecular mechanisms linked to pathophysiology of mood disorders are not yet fully elucidated. In recent years there has been a growing recognition that changes in the immune system, oxidative stress and neurotrophic factors could contribute to the development of mood episodes. The diagnosis of Bipolar disorder is a challenge to be recognized due to the high degree of overlap of symptoms, which are presented by a patient during bipolar depressive episode and correlate with the diagnostic criteria for major depression. In this context, the search for peripheral markers for psychiatric disorders has followed for many years, yet remains undefined. Objective: As a result, this study aims to search for peripheral markers for use in aiding the differential diagnosis of unipolar and bipolar depression. Methods: To this end, we measured serum levels of BDNF; IL-2, IL-4, IL-6, IL-10, TNF, IFN-P, IL-17, damage to lipids and proteins in 54 depressive Bipolar and Unipolar outpatients matched to 54 healthy volunteers. Depressive episode was assessed using the Hamilton Depression Rating Scale (HDRS). Results: In this study we found increased interleukin-6 in both groups compared to controls (p = 0.020 and p = 0.001, respectively), as well as increased damage to proteins in unipolar patients (p = 0.003). There were no changes in BDNF levels in both groups of patients (p = 0.295) and the content of lipid peroxidation (p = 0.860). A positive correlation was found between the values of HDRS and protein carbonyl levels (r = 0.291, p = 0.036) in bipolar patients. Conclusion: Our results indicate the involvement of oxidative stress, for damage to proteins, and a change in the inflammatory immune system in depressed patients; however the markers evaluated here were not suitable for differentiation of unipolar and bipolar depressive disorders, more research is needed, with a larger sample to validate these findings.

nÃo hà / O objetivo do estudo foi investigar o perfil de produÃÃo de IL-6 em pacientes com tuberculose pulmonar ativa e avaliar o papel funcional do polimorfismo -174G>C do gene de IL-6 na produÃÃo sistÃmica desta citocina. Um total de 63 pacientes e 99 controles foi estudado, sendo 38 pacientes [25(65,8%) masculinos] e 63 controles [51 (81%) masculinos] para a dosagem de IL-6, enquanto, 42 pacientes [25 (60%) masculinos] e 79 controles [62(78,5%) masculinos] para o estudo do polimorfismo. Os pacientes foram selecionados dos centros de referÃncia da rede estadual de saÃde: Dona LibÃnia, Hospital de Messejana, Hospital de Maracanaà e Hospital Geral Dr. CÃsar Cals. O grupo controle foi selecionado no HEMOCE. Foi realizado teste de ELISA para a dosagem sÃrica de IL-6. O DNA genÃmico foi extraÃdo de sangue perifÃrico e o polimorfismo de IL-6 foi estudado por reaÃÃo de polimerase em cadeia utilizando iniciadores seqÃÃncia especÃficos. A dosagem sÃrica de IL-6 se mostrou elevada nos pacientes portadores de tuberculose em relaÃÃo aos controles (mediana = 4,3 pg/mL versus 0,5 pg/mL, p<0,001), porÃm nÃo exibiu diferenÃa entre os grupos de doentes sensÃveis e os resistentes ao tratamento especÃfico. Em relaÃÃo ao estudo funcional do polimorismo de IL-6, foi observado um robusto aumento dos nÃveis de IL-6 nos doentes portadores do genÃtipo GG (mediana=4,1 pg/mL, variaÃÃo 0,5-12,0 pg/mL), em relaÃÃo aos portadores dos genÃtipos GC e CC, sendo que nestes se observou uma expressÃo de IL-6 semelhante a dos controles (mediana=0,6 pg/mL, variaÃÃo 0,0-2,8 pg/mL), conferindo significÃncia estatÃstica com p=0,04. A relevÃncia deste estudo à mostrar in vivo o papel funcional do polimorfismo de IL-6 na tuberculose. Em conclusÃo, o genÃtipo GG de pacientes com tuberculose pulmonar ativa determina produÃÃo aumentada de IL-6. / The aim of this study was to investigate the profile of IL-6 production in patients with active pulmonary tuberculosis and to evaluate the functional role of polymorphism -174G>C in the systemic production of this cytokine. A total of 63 patients and 99 controls were studied. Among them 38 patients [25(65.8%) males] and 63 controls [51(81%) males] were studied for the IL-6 dosage. Moreover, 42 patients [25(60%) males] and 79 controls [62(78.5%) males] were studied for the -174G>C polymorphism. Patients were selected from Dona LibÃnia Center; Messejana Hospital, Maracanau Hospital and Dr. Cesar Cals General Hospital. The control group was selected from HEMOCE. An ELISA test was performed to measure IL-6 in peripheral blood. The genomic DNA was extracted from peripheral blood and IL-6 polymorphism was studied by polymerase chain reaction using sequence-specific primers. The IL-6 dosage showed an increase in patients with tuberculosis in relation to controls (An increase in IL6 dosage was found in patients with tuberculosis in relation to controls) (median= 4.3 pg/mL vs 0.5 pg/mL, p<0.001), but no difference was observed in drug-sensitive patients in comparison to drug-resistant ones. The genotype distribution showed no difference between patients and controls. In relation to the functional study, the IL-6 levels pointed out a significant increase in patients presenting GG genotype (median=4.1 pg/mL, range 0.5-12.0 pg/mL), in relation to GC and CC careers; these two latter genotypes presented similar IL-6 production as in healthy individuals with median=0.6 pg/mL, range 0.0-2.8 pg/mL, corroborating statistical significance with p=0.04. The relevance of this study is to show in vivo the functional role of IL-6 polymorphism in active pulmonary tuberculosis. Conclusion, the GG genotype in patients with pulmonary tuberculosis determines an increase in IL-6 systemic production.

A interleucina-6 (IL-6) é uma citocina com dupla função na sensibilidade à insulina. O objetivo desse estudo foi investigar o efeito da IL-6 durante 1 e 24 horas no metabolismo de células musculares resistentes à insulina. Em células de indivíduos saudáveis, 1 hora de exposição à IL-6 aumentou a síntese de glicogênio e a captação de glicose além de pJAK2 e pSTAT3, mas não em células de diabéticos tipo 2. Diferentemente, a IL-6 aumentou a oxidação de ácido graxo em ambos os grupos. Por outro lado, em células musculares da linhagem L6, a IL-6, em 24 horas, reduziu a síntese de glicogênio e a captação de glicose em condições normais, mas não em células resistentes à insulina. Além de reduzir pJak2, pStat3 e pAkt. A IL-6 aumentou oxidação de ácido graxo e pACC em ambos os grupos. Sendo assim, células musculares resistentes à insulina apresentam uma resposta alterada ao efeito da IL-6. Nessas células, o efeito dessa citocina está abolido no metabolismo de carboidratos mas permanece efetivo no lipídico. / Interleukin-6 (IL-6) is a cytokine with a dual role in modulating insulin sensitivity. The aim of this study was to investigate the effect of IL-6 exposure for 1 hour and 24 hours on metabolism of insulin-resistant skeletal muscle cells. In muscle cells from healthy subjects, 1 hour of exposure to IL-6 increased glycogen synthesis, glucose uptake, pJAK2 and pSTAT3, which were not observed in muscle cells of type 2 diabetic subjects. In contrast, IL-6 increased fatty acid oxidation in cells from both groups. On the other hand, in skeletal muscle cell line L6, IL-6 for 24 hours reduced glycogen synthesis and glucose uptake in normal conditions, which were not observed in insulin-resistant L6 cells. In addition, pJak2, pStat3 and pAkt were reduced in insulin-resistant cells. In contrast, IL-6 increased fatty acid oxidation and pACC in both groups. Therefore, insulin resistant skeletal muscle cells have an altered response to the effect of IL-6. On these cells, the effect of IL-6 is abolished on carbohydrate metabolism, while remaining effective on lipid metabolism.

Orientador: Rebeca de Souza Azevedo / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-23T13:31:17Z (GMT). No. of bitstreams: 1 Messetti_AnaCamilaPereira_M.pdf: 2046118 bytes, checksum: 6767fe84e5b25d194bac897de86b23a3 (MD5) Previous issue date: 2013 / Resumo: A doença periodontal (DP) é uma doença inflamatória crônica de ampla distribuição etária e mundial, que resulta da interação entre fatores etiológicos heterogêneos e que pode sofrer influência ambiental e sistêmica, especialmente na presença do diabetes melito (DM). Os mecanismos que envolvem a associação entre o DM e a presença da DP ainda não estão completamente elucidados, mas as características genéticas ou epigenéticas do hospedeiro, como os polimorfismos genéticos, podem influenciar esta relação. Dessa forma, o objetivo deste estudo foi avaliar o envolvimento de polimorfismos nos genes de IL1-? (-889), de IL1-? (+3984), de IL-6 (-174), de TNF-? (-308) e da paraoxanase (-192) e da paraoxonase (-55) no desenvolvimento de DP e DM em um grupo de pacientes brasileiros. Os polimorfismos rs1800587 e rs1143634 no gene IL-1, rs1800796 no gene IL6, rs1800629 no gene TNF-?, e rs662 e rs854560 no gene paraoxanase foram genotipados em 302 adultos, dos quais 96 eram diabéticos com DP (ADM+DP), 20 eram diabéticos com saúde periodontal (ADM-DP), 112 eram normoglicêmicos com DP (AN+DP) e 74 eram normoglicêmicos com saúde periodontal (AN-DP); e em 88 crianças e adolescentes, dos quais 11 eram diabéticos com gengivite (CDM+G), 15 eram diabéticos com saúde gengival (CDM-G), 30 eram normoglicêmicos com gengivite (CN+G) e 32 eram normoglicêmicos com saúde gengival (CN-G). No grupo de pacientes adultos, a presença do alelo T no polimorfismo rs1143634 no gene IL1-? foi mais frequente nos indivíduos ADM+DP que nos indivíduos AN-DP, gerando um OR de 14,9 (95% IC: 8,6-25,9; p<0,0001); a presença do alelo A no polimorfismo rs1800629 no gene TNF-? foi mais frequente nos indivíduos ADM+DP que nos indivíduos AN-DP, gerando um OR de 22,7 (95% IC: 6,96 -74,5 p<0,0001), e a presença do alelo C no polimorfismo rs1800796 no gene IL6 foi mais frequente nos indivíduos ADM+DP que nos indivíduos AN+DP, gerando um risco de recorrência de 2,38 (95% IC:1,61-3,5; p<0,0001), e que nos indivíduos AN-DP, gerando risco de recorrência de 2,87 (1,79-4,5; p<0,0001). No grupo de pacientes crianças e adolescentes, a presença do alelo C no polimorfismo rs1800796 no gene IL-6 foi mais frequente em indivíduos CN+G que nos indivíduos CN-G, gerando um risco de recorrência de 121,1 (95% IC:32,3-145,3; p<0,0001), e foi mais frequente nos indivíduos CDM+G que nos indivíduos CN-G, gerando um risco de recorrência de 104 (95% IC:11,4-136,6; p<0,0001). Os resultados deste estudo evidenciam a associação dos polimorfismos rs1143634 no gene IL1-?, rs1800796 no gene IL6 e rs1800629 no gene TNF-? com a suscetibilidade genética ao desenvolvimento de DP e/ou DM na população adulta estudada; e a associação do polimorfismo rs1800796 no gene IL-6 com a suscetibilidade genética ao desenvolvimento de DP e/ou DM na população de crianças e adolescentes estudada / Abstract: Periodontal disease (PD) is a chronic inflammatory disease of worldwide distribution that may affect all age groups, and results from the interaction between heterogeneous etiologic factors, such as environmental and systemic influence, especially in the presence of diabetes mellitus (DM). Mechanisms involving the association between DM and the presence of PD are still not fully elucidated, but the genetic or epigenetic alterations of the host, such as the genetic polymorphisms may influence this relationship. Thus, the aim of this study was to evaluate the involvement of polymorphisms in the genes of IL1-? (-889), IL1- (+3984), IL-6 (-174), TNF-? (-308) and paraoxanase (-192) and paraoxonase (-55) in PD and/or DM development in a group of Brazilian patients. The polymorphisms rs1800587 and rs1143634 from IL1 gene, rs1800796 form IL6 gene, rs1800629 from TNF-? gene, and rs662 and rs854560 from paraoxanase gene were genotyped in 302 adults, of whom 96 were diabetic with PD (ADM+PD), 20 were diabetics with periodontal health (ADM-PD), 112 were normoglycemic with PD (AN+PD) and 74 were normoglycemic with periodontal health (AN-PD); and in 88 children and adolescents, of whom 11 were diabetic patients with gingivitis (CDM+G), 15 were diabetics with gingival health (CDM-G), 30 were normoglycemic with gingivitis (CN+G) and 32 were normoglycemic with gingival health (CN-G). In the group of adult patients, the presence of T allele at the rs1143634 polymorphism in the IL1-? gene was more frequent in ADM+PD than in AN-PD, generating an OR of 14, 9 (95% CI :14,9-25, 9; p <0.0001), the presence of A allele at the rs1800629 polymorphism in the TNF-? gene was more frequent in ADM+PD than in AN+PD, generating an OR of 22,7 (95% CI 6.96 -74.5; p <0.0001), and the presence of C allele at the rs1800796 polymorphism in the gene IL6 was more frequent in ADM+PD than in AN+PD, generating an OR of 2.38 (95% CI :1,61-3, 5; p <0.0001), and it was more frequent in ADM+PD than in AN-PD, generating an OR of 2.87 (1.79 to 4.5, p <0.0001). In the group of children and adolescents, the presence of C allele at the rs1800796 polymorphism in the IL6 gene is more frequent in NC+G than in NC-G, generating an OR of 121.1 (95% CI :32,3-145, 3; p <0.0001), and it was more frequent in CMD+G than in NC-G, generating an OR of 104 (95% CI :11,4-136,6; p <0.0001). The results of this study show the association of rs1143634 polymorphisms in the IL1-? gene, rs1800796 in the IL6 gene, and rs1800629 in the TNF-? gene with genetic susceptibility to PD and/or DM development in the adult population studied, and association of the polymorphism rs1800796 in the IL6 gene with genetic susceptibility for PD and/or DM development in the children and adolescents population studied / Mestrado / Estomatologia / Mestra em Estomatopatologia

Orientadores: Sérgio Tadeu Martins Marba, Maria Marluce dos Santos Vilela / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-19T19:35:04Z (GMT). No. of bitstreams: 1 Caldas_JamilPedrodeSiqueira_D.pdf: 1222861 bytes, checksum: f1f27f58131a25e1222f77de30548e3e (MD5) Previous issue date: 2011 / Resumo: O objetivo do estudo foi avaliar a associação entre marcadores de estresse oxidativo e de inflamação ao nascimento e o desenvolvimento de hemorragia peri e intraventricular (HPIV) em recém-nascidos pré-termo de muito baixo peso ao nascer (RNPTMBP). Estudo de coorte envolvendo todos os RNPTMBP nascidos no CAISM-UNICAMP entre maio de 2009 a outubro de 2010. Excluíram-se aqueles dos quais não se obteve a amostra de sangue, os com malformação grave do sistema nervoso central e os que morreram antes de seis horas de vida. A coleta de sangue de cordão umbilical foi realizada diretamente da placenta ainda implantada, tendo sido dosados a produção basal e estimulada de intermediários reativos de oxigênio (ROI) por leucócitos polimorfonucleares e o níveis séricos de glutationa reduzida (GR) e interleucina-6 (IL-6). A HPIV foi diagnosticada por ecografia transfontanelar seriada - 6, 12, 24 e 72 horas de vida e com 7 e 28 dias de vida; classificada segundo Papile et al. (1978). Dados maternos, do parto e do RN foram considerados como variáveis independentes de controle. A distribuição dos acometidos por HPIV foi dada por frequência. Os valores de ROI, GR e IL-6 foram expressos como mediana e percentis 25 e 75. As variáveis categóricas foram avaliadas por teste de qui-quadrado ou Fisher, e teste de Mann-Withney para comparação das medianas de ROI, GR e de IL-6 entre os RNs com e sem HPIV...Observação: O resumo, na íntegra, poderá ser visualizado no texto completo da tese digital / Abstract: This study evaluated the relationship between four laboratorial tests of oxidative stress and inflammatory markers and the development of intraventricular and periventricular hemorrhage (IVH) in very low birth weight infants (VLBW) - less than < 1.500 g at birth. Cohort study accomplished in a neonatal intensive care at CAISM-UNICAMP, from May 2009 to October 2010. Infant with severe brain malformations, death before 6 hours of life and those whose umbilical blood samples weren't obtained were excluded. Basal and under stimulation production of reactive intermediaries of oxygen (BROI and SROI), reduced glutathione (RG) and interleukin-6 (IL-6) were evaluated from umbilical blood. IVH was diagnosed by serial transfontanellar brain ultrasonography and classified according to Papile et al (1978). It was made at 6,12, 24, 72 hours of life and 7 and 28 days of life. Maternal factors, labor and delivery characteristics, and neonatal parameters were considered control independent variables and they were expressed in frequency. BROI, SROI, RG and Il-6 levels were expressed in medians and 25 and 75 percentiles. Chi-square or Fisher tests were used to determine the association of categorical variables and IVH. Mann-Whitney test were used to compare IVH and non-IVH groups and laboratorial markers medians. Univariate analysis was performed to identify differences between the IVH and non-IVH groups...Note: The complete abstract is available with the full electronic document / Doutorado / Pediatria / Doutor em Saude da Criança e do Adolescente

Orientador: Suzana Erico Tanni / Resumo: Introdução: As manifestações sistêmicas da Doença Pulmonar Obstrutiva Crônica (DPOC) estão relacionadas ao aumento do processo inflamatório sistêmico, entretanto, não está totalmente esclarecido o quanto a inflamação sistêmica, em especial a interleucina-6 (IL-6), está associada com o risco de mortalidade. Dessa forma, o objetivo desse estudo consistiu em avaliar a evolução das concentrações séricas da IL-6 e sua associação com a mortalidade de pacientes com DPOC em nove anos. Pacientes e métodos: 133 pacientes foram avaliados no momento basal entre 2004 e 2006 e reavaliados depois de três e nove anos por meio de avaliação clínica, espirometria, oximetria de pulso e gases arteriais, composição corporal, distância percorrida em seis minutos (DP6), qualidade de vida, intensidade de dispneia, Índice BODE, comorbidades, IL-6 e número de exacerbações nos três primeiros anos de seguimento. Resultados: Durante acompanhamento, 19 pacientes perderam seguimento, quatro não tiveram a causa da morte identificada e 18 estavam com dados incompletos; assim, 92 pacientes foram incluídos na análise de mortalidade tendo a IL-6 como covariável tempo dependente. Na reavaliação dos sobreviventes, 64 pacientes morreram, 23 perderam seguimento, 12 recusaram continuar participando e um não pode ser reavaliado em decorrência de exacerbações frequentes; dessa forma, 33 foram incluídos na reavaliação após nove anos. Sobre o perfil inflamatório, nos pacientes que sobreviveram após nove anos, houve aumen... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Introduction: Systemic manifestations of Chronic Obstructive Pulmonary Disease (COPD) are related to increased systemic inflammatory process; however, it is not entirely clear how the systemic inflammation, in particular interleukin-6 (IL-6), is associated with mortality risk. Therefore, this study aimed to evaluate the evolution of serum IL-6 concentrations and its association with mortality of COPD patients over nine years. Patients and methods: 133 COPD patients were assessed at baseline between 2004 and 2006 and reassessed after three and nine years through clinical evaluation, spirometry, pulse oximetry and arterial gases, body composition, 6-minute walk distance (6MWD), quality of life, dyspnea intensity, BODE Index, comorbidities, IL-6 and number of exacerbations in the first three years of follow-up. Results: After nine years, 19 patients lost the follow-up, was not possible to identify the date of death of 4 patients and 18 had incomplete data; thus, 92 patients were included in the Cox mortality analysis with IL-6 as a time dependent covariate. In the reassessment of survivors, 64 patients died, 23 lost the follow-up, 12 refused to participate and 1 could not be involved due to recurrent exacerbations; therefore, 33 patients were included in the reassessment after nine years of followup. Regarding the inflammatory profile, in patients who survived after nine years, there was a significant increase in IL-6 [0.4(0.2-0.8) vs 5.7(3.4-11)pg/mL; p<0.001] and reduction in ... (Complete abstract click electronic access below) / Doutor

Orientador: Paulo Sérgio Cerri / Resumo: OBJETIVO: Avaliar a reação tecidual e bioatividade provocada por NeoMTA Plus e MTA Fillapex em subcutâneo de ratos. MATERIAL E MÉTODOS: Para este estudo foram utilizados 60 ratos Holtzman, sendo distribuídos aleatoriamente em três grupos (n= 20): NeoMTA Plus (Avalon Biomed Inc. Bradenton, FL, EUA), MTA Fillapex (Angelus Ciência e Tecnologia, Londrina - PR – Brasil) e Controle (tubos de polietileno vazios). Para avaliar a reação tecidual provocada pelos materiais, foram implantados tubos de polietileno preenchidos com os cimentos endodônticos no tecido conjuntivo do subcutâneo na região dorsal dos ratos. No grupo controle (GC), tubos de polietileno vazios foram implantados. Após os períodos de 7, 15, 30 e 60 dias, cinco animais de cada grupo por período foram eutanásiados e os tubos implantados com os tecidos adjacentes foram removidos e submetidos ao processamento para inclusão em parafina. A partir dos cortes corados com HE, foram realizadas análises morfológicas, mensuração da espessura da cápsula e densidade numérica de células inflamatórias. Os cortes foram também submetidos à reação imuno-histoquímica para detecção de interleucina-6 (IL-6), uma citocina pró-inflamatória, e o número de células imunopositivas foi computado. A quantidade de colágeno nas cápsulas foi estimada a partir de cortes submetidos ao método do picrosirius-red e analisados sob luz polarizada. A bioatividade dos cimentos endodônticos foi avaliada por meio da reação histoquímica von Kossa e a análise so... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: To evaluate the tissue reaction and bioactivity caused by NeoMTA Plus and MTA Fillapex in connective tissue of subcutaneous. MATERIAL AND METHODS: For this study, 60 Holtzman male rats were used, which were randomly distributed in three groups (n = 20): NeoMTA Plus (Avalon Biomed Inc. Bradenton, FL, USA), MTA Fillapex (Angelus Ciência e Tecnologia, Londrina - PR - Brazil) and Control (empty polyethylene tubes). To verify the tissue reaction caused by root canal sealers, the polyethylene tubes were filled with endodontic sealers and were implanted into dorsal subcutaneous tissues. In the control group (CG), empty polyethylene tubes were implanted. After 7, 15, 30 and 60 days, five animals from each group per period were sacrificed and implants surrounded by tissues were removed and processed for paraffin-embedding. From HE-stained sections, the morphological analysis, measurement of capsule thickness and numerical density of inflammatory cells were carried out. Sections were also subjected to immunohistochemical reaction to detect interleukin-6, a pro-inflammatory cytokine, and the number of immunopositive cells was computed. The amount of collagen in the capsules was measured in the sections stained with picrosirius-red method and analyzed under polarized light. The bioactivity of endodontic sealers was evaluated by von Kossa histochemical reaction and the analysis of under polarized light. The data were submitted to two-way ANOVA and post-hoc Tukey test (p < 0.05). RESULTS: ... (Complete abstract click electronic access below) / Doutor

Multiple myeloma is an incurable fatal neoplasm of plasma cells affecting mainly elderly people. There are many research laboratories in the world where multiple myeloma is studied. Permanent cell lines are indispensable tools for both basic and applied research. However, the establishment of new cell lines is difficult with poor success. We established 96 primary cultures of bone marrow samples from myeloma patients. Only one culture succeeded in permanet myeloma cell line. The novel plasmacytic cell line ÚHKT-893 was established from bone marrow sample of 57 years old female relapsed with multiple myeloma of IgGκ isotype. The cell line is however dependent on the continuous presence of interleukin-6 in culture media. ÚHKT-893 cells grow continuously already more than 1 year. The growth of cells was regularly monitored according to growth curves and by measurement of cell viability. Surface antigenic profile was repeatedly determined by flow cytometry. The simultaneous expression of both CD138 and CD38 surface molecules confirmed the plasma cell origin of cells. The establishment of the ÚHKT-893 myeloma cell line will extend the panel of existing myeloma cell lines as a new ex vivo model for the study of the etiology and pathogenesis of multiple myeloma. It will also provide the source of new...

Human mast cells are often found perivascularly and at mucosal sites and may play crucial roles in the inflammatory response. Recent studies have suggested a prominent role for mast cells in host defense. In this study, we analyzed the effects of a common airway pathogen, Moraxella catarrhalis and a commensal bacterium, Neiserria cinerea, on activation of human mast cells. Human mast cell leukemia cells (HMC-1) were activated with either phorbol myristate acetate (PMA) and calcium ionophore or with varying concentrations of heat-killed suspensions of bacteria. Supernatants were assayed for the cytokines interleukin-4 (IL-4), granulocyte macrophage colony stimulating factor (GM-CSF), IL-6, IL-8, IL-13 and monocyte chemotactic protein-1 (MCP-1). Nuclear proteins were isolated and assayed by electrophoretic mobility shift assay (EMSA) for nuclear factor kappaB (NF-κB) nuclear binding activity. In some experiments, NF-κB inhibitor, Bay-11 was added to determine functional significance. Both M. catarrhalis and N. cinerea induced mast cell activation and selective secretion of two key inflammatory cytokines, IL-6 and MCP-1. This was accompanied by NF-κB activation. Neither spun bacterial supernatants nor bacterial lipopolysaccharide induced cytokine secretion, suggesting need for direct bacterial contact with mast cells. Scanning electron microscopy revealed active aggregation of bacteria over mast cell surfaces. The NF-κB inhibitor, Bay-11, inhibited expression of MCP-1. These findings suggest the possibility of direct interactions between human mast cells and common bacteria and provide evidence for a novel role for human mast cells in innate immunity.

Host sensors that recognize pathogen associated molecular patterns and the mechanisms of innate immune response to mouse polyomavirus (MPyV) infection were the main topics of current work. We found that MPyV did not induce interferon (IFN) production during early events of infection, but induced interleukin-6 (IL-6) and other cytokine production without inhibiting virus multiplication. Cytokine microenvironment changed the phenotype of adjacent non infected fibroblasts toward the cancer-associated fibroblast (CAF)-like phenotype. We identified Toll-like receptor 4, a sensor of the innate immunity system, to be responsible for infection dependent IL-6 production. In an effort to determine whether and where virions are released from endosomal compartments into the cytosol, we found that the hydrophobic domains of minor capsid proteins, exposed on the surface of virions after their partial disassembly in the ER, play an important role in effective escape of virions from the lumen part of endoplasmic reticulum into the cytosol, Although naked, partially disassembled virions appear before translocation to the nucleus in the cytosol, viral DNA is not recognized by cytosolic sensors at this phase of infection Sensing of MPyV resulting in IFN production occurs first during viral replication. Mutant virus,...