Efeito do tratamento com a proteína quimérica IL-13PE sobre a inflamação pulmonar induzida por partículas de sílica em camundongos

A interleucina 13 (IL-13) tem sido apontada como um dos principais mediadores em processos de ativação de fibroblastos e indução de fibrose pulmonar, sendo, portanto, considerada como um alvo terapêutico importante. A silicose é uma doença pulmonar inflamatória crônica, de caráter ocupacional, caracterizada por uma intensa resposta fibrótica e granulomatosa. Com base nestas observações, tivemos por objetivo investigar o potencial efeito da administração da imunotoxina IL-13-PE38QQR (IL-13PE) sobre o modelo de silicose em camundongos. Camundongos Swiss-Webster foram anestesiados e instilados intranasalmente com partículas de sílica (10 mg), sendo a administração da IL-13PE (200ng/dia) realizada por via intranasal, uma vez ao dia em dias alternados no período entre 21 a 27 dias após a provocação. Analisamos o componente inflamatório, a deposição de colágeno e a área de granuloma avaliados através de técnicas clássicas de histologia, incluindo coloração com H&E e Picrus-sirius, ou ainda a quantificação do conteúdo de colágeno por Sircol. Os componentes de matriz extracelular fibronectina e laminina foram avaliados através de imunohistoquímica. Citocinas e quimiocinas foram quantificadas por sistema de ELISA. As medidas de função pulmonar e resposta de hiperreatividade foram realizadas através do sistema de pletismografia de corpo inteiro invasiva. Verificamos que o tratamento curativo com a IL-13PE inibiu de forma acentuada o comprometimento da função pulmonar nos camundongos silicóticos, incluindo tanto aumento da resistência como da elastância, assim como a resposta de hiperratividade das vias aéreas ao agente broncoconstrictor metacolina. De forma coerente, os animais silicóticos quando submetidos ao tratamento com IL-13PE apresentaram marcada redução do componente inflamatório pulmonar e da resposta fibrótica, atestado pela diminuição na produção de colágeno, laminina e fibronectina e redução importante da área de granuloma. De forma semelhante, as citocinas (TNF-α e TGF-) e quimiocinas (MIP-1α, MIP-2, TARC, IP-10, MDC) detectadas em quantidade aumentada no pulmão de animais silicóticos foram reduzidas pelo tratamento com a IL-13PE. Em conclusão, nossos resultados mostram que a administração curativa da IL-13PE foi capaz de inibir os componentes inflamatórios e fibróticos da fase crônica do quadro silicótico em camundongos, o que se refletiu de forma clara na melhora da função pulmonar. Em conjunto, nossos achados indicam que a utilização da IL13PE parece constituir uma abordagem terapêutica extremamente promissora para aplicação em casos de doenças crônicas de natureza fibrótica como a silicose.

草鱼、中华鳖脾细胞培养上清液IL-2物质的检测

用刀豆蛋白A(ConA)刺激诱导草鱼和中华鳖脾细胞 ,收集细胞培养上清液 ,用小鼠胸腺细胞增殖试验和对小鼠L92 9细胞系杀伤试验检测上清液中白细胞介素 2 (简称IL 2 )活性。结果表明 :草鱼、中华鳖脾细胞培养上清液中有IL 2样活性物质 ,这种物质使小鼠的胸腺细胞3H TdR掺入量明显增加 ,在相同效靶比的条件下对小鼠L92 9细胞系杀伤率也显著增强 ,这种IL 2活性均能被抗人rIL 2血清所抑制。中华鳖脾细胞培养上清液 (含IL 2 )对中华鳖胸腺细胞也有较明显的促增殖作用并能消除兔抗中华鳖胸

Revisiting human IL-12Rβ1 deficiency: A survey of 141 patients from 30 countries

Interleukin-12 receptor β1 (IL-12Rβ1) deficiency is the most common form of Mendelian susceptibility to mycobacterial disease (MSMD). We undertook an international survey of 141 patients from 102 kindreds in 30 countries. Among 102 probands, the first infection occurred at a mean age of 2.4 years. In 78 patients, this infection was caused by Bacille Calmette-Guérin (BCG; n = 65), environmental mycobacteria (EM; also known as atypical or nontuberculous mycobacteria) (n = 9) or Mycobacterium tuberculosis (n = 4). Twenty-two of the remaining 24 probands initially presented with nontyphoidal, extraintestinal salmonellosis. Twenty of the 29 genetically affected sibs displayed clinical signs (69%); however 8 remained asymptomatic (27%). Nine nongenotyped sibs with symptoms died. Recurrent BCG infection was diagnosed in 15 cases, recurrent EM in 3 cases, recurrent salmonellosis in 22 patients. Ninety of the 132 symptomatic patients had infections with a single microorganism. Multiple infections were diagnosed in 40 cases, with combined mycobacteriosis and salmonellosis in 36 individuals. BCG disease strongly protected against subsequent EM disease (p = 0.00008). Various other infectious diseases occurred, albeit each rarely, yet candidiasis was reported in 33 of the patients (23%). Ninety-nine patients (70%) survived, with a mean age at last follow-up visit of 12.7 years ± 9.8 years (range, 0.5-46.4 yr). IL-12Rβ1 deficiency is characterized by childhood-onset mycobacteriosis and salmonellosis, rare recurrences of mycobacterial disease, and more frequent recurrence of salmonellosis. The condition has higher clinical penetrance, broader susceptibility to infections, and less favorable outcome than previously thought. © 2010 Lippincott Williams & Wilkins.

Le changement de qualification d'un bien en cours de régime matrimonial est-il permis?

Article publié avec l'autorisation de la Chambre des notaires du Québec

Politiques sociales au Canada : le fédéralisme a-t-il un effet conservateur ?

Éditorial du 27 février 2015

Los juegos en La Il??ada y en La Eneida

Se hace un estudio comparativo y una descripci??n de las competiciones atl??ticas que aparecen en las obras de Homero y Virgilio, la Il??ada y la Eneida, respectivamente. En la Eneida, Virgilio adopta muchos elementos hom??ricos, sin embargo, los adopta a rasgos y aspectos propios de su ??poca.

Il paesaggio come strumento educativo. 'El paisaje como instrumento educativo'.

Monográfico con el título: 'Patrimonio y Educación'. Resumen basado en el de la publicación

Endurance training induces depot-specific changes in IL-10/TNF-alpha ratio in rat adipose tissue

White adipose tissue (WAT) is the source of pro- and anti-inflammatory cytokines and recently, it has been recognized as an important source of interleukin 10 (IL-10). Acute physical exercise is known to induce an anti-inflammatory cytokine profile, however, the effect of chronic physical exercise on the production of IL-10 by WAT has never been examined. We assessed IL-10 and TNF-alpha concentration in WAT of rats engaged in endurance training. Animals were randomly assigned to either a sedentary control group (S, n = 7) or an endurance trained group (T, n = 8). Trained rats ran on a treadmill 5 days/wk for 8 wk (55-65% VO(2max). Detection of IL-10 and TNF-alpha protein and mRNA expression, as well as the gene expression of PPAR-gamma, and immunocytochemistry to detect mononuclear phagocytes were carried out. A reduction in absolute retroperitoneal adipose tissue (RPAT) weight in T (44%; p < 0.01), when compared with S was observed. IL-10 concentration was increased (1.5-fold, p < 0.05), to a higher extent than that of TNF-alpha (66%. p < 0.05) in the mesenteric adipose tissue (MEAT) of the trained group, while no change related to training was observed in RPAT. In MEAT, IL-10/TNF-alpha ratio was increased in T, when compared with S (30%; p < 0.05). PPAR-gamma gene expression was increased in T (1.1-fold; p < 0.01), when compared with S in the same adipose depot. No monocyte infiltration was found. In conclusion, exercise training induced increased IL-10 expression in the mesenteric depot, resulting in a modified IL-10/TNF-alpha ratio. We also conclude that WAT presents a depot-specific response to endurance training regarding the studied aspects. (C) 2008 Elsevier Ltd. All rights reserved.

Sintomatologia depressiva e avaliação de níveis de TNFα IL-2 em indivíduos idosos e com doença pulmonar obstrutiva crônica

The aim of the present study was to assess the presence of depressive symptomatology among elderly residents in long-stay institutions (LSI) and in the community of Recife, Brazil. In total, 81 long-stay elderly patients (mean age of 75.55 ± 9.18 years) and 132 elderly (mean age of 73.14 ± 8.27 years) individuals from the community were evaluated. Depressive symptomatology was assessed by the Geriatric Depression Scale (GDS-15), cognitive status by the Mini Mental State Examination (MMSE) and capacity to perform the activities of daily living (ADL) by the Katz Index. Comorbities and the use of medication were recorded. The LSI elderly exhibited more depressive symptoms (p < 0.001) and more dependency (p< 0.001). We observed no differences in MMSE (p = 0.058). The elderly in the community displayed more comorbidities and the LSI elderly consumed more medication (p < 0.001 and p < 0.001, respectively). According to multivariate analysis (logistic regression), being male, having no spouse and having a low schooling level are risk factors for depressive symptoms. In conclusion, most elderly with depressive symptoms received no medication fordepression.