The objective of this study was to investigate the catalytic activity of basic aminopeptidase (APB) and its association with periarticular edema and circulating tumor necrosis factor (TNF)-alpha and type II collagen (CII) antibodies (AACII) in a rat model of rheumatoid arthritis (RA) induced by CII (CIA). Edema does not occur in part of CII-treated, even when AACII is higher than in control. TNF-alpha is detectable only in edematous CII-treated. APB in synovial membrane is predominantly a membrane-bound activity also present in soluble form and with higher activity in edematous than in non-edematous CII-treated or control. Synovial fluid and blood plasma have lower APB in non-edematous than in edematous CII-treated or control. In peripheral blood mononuclear cells (PBMCs) the highest levels of APB are found in soluble form in control and in membrane-bound form in non-edematous CII-treated. CII treatment distinguishes two categories of rats: one with arthritic edema, high AACII, detectable TNF-alpha, high soluble and membrane-bound APB in synovial membrane and low APB in the soluble fraction of PBMCs, and another without edema and with high AACII, undetectable TNF-alpha, low APB in the synovial fluid and blood plasma and high APB in the membrane-bound fraction of PBMCs. Data suggest that APB and CIA are strongly related.

Chronic inflammatory diseases are triggered by causal stimuli that might occur long before the appearance of the symptoms. Increasing evidence suggests that these stimuli are necessary but not always sufficient to induce the diseases. The murine model of type II collagen emulsified in Freund's incomplete adjuvant (collagen‐induced arthritis) to induce rheumatoid arthritis (RA) follows this pattern as some animals do not develop the chronically inflamed phenotype. Considering that in the immune–pineal axis (IPA) theory adrenal–pineal cross‐talk adjusts early phases of inflammatory processes, we investigated whether differences in IPA activation could explain why some animals are resistant (RES) while others develop RA. We observed a similar increase in 6‐sulfatoxymelatonin (aMT6s) excretion from day 3 to 13 in both RES and RA animals, followed by a significant decrease in RA animals. This pattern of aMT6s excretion positively correlated with plasma corticosterone (CORT) in RES animals. Additionally, RA animals presented a lower aMT6s/CORT ratio than saline‐injected or RES animals. Plasmatic levels of tumour necrosis factor were similar in both groups, but interleukin (IL)‐1β and monocyte chemotactic protein 1 (MCP‐1) levels were lower in RES compared to RA animals. IL‐2 and IL‐4 were decreased in RES animals compared to saline‐injected animals. The aMT6s/CORT ratio inversely correlated with the paw thickness and the inflammatory score (levels of IL‐1β, MCP‐1, IL‐2 and IL‐4 combined). Thus, adrenocortical–pineal positive interaction is an early defence mechanism for avoiding inflammatory chronification. Key points Immune–pineal axis imbalance is observed in early‐phase rheumatoid arthritis development. Only resistant animals present a positive association between adrenal and pineal hormones. The 6‐sulfatoxymelatonin/corticosterone ratio is decreased in animals that develop rheumatoid arthritis. The inflammatory score combining the levels of nocturnal interleukin (IL)‐1β, monocyte chemotactic protein 1, IL‐2 and IL‐4 presents a very strong positive correlation with the size of inflammatory lesion. The 6‐sulfatoxymelatonin/corticosterone ratio presents a strong negative correlation with the inflammatory score and paw oedema size.

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Protein (western blotting) and gene (PCR) expressions, catalytic activity of puromycin-insensitive membrane-bound neutral aminopeptidase (APM/CD13) and in situ regional distribution of CD13 and FOS immunoreactivity (ir) were evaluated in the hypothalamus of monosodium glutamate obese (MSG) and/or food deprived (FD) rats in order to investigate their possible interplay with metabolic functions. Variations in protein and gene expressions of CD13 relative to controls coincided in the hypothalamus of MSG and MSG-FD (decreased 2- to 17-fold). Compared with controls, the reduction of hypothalamic CD13 content reflected a negative balance in its regional distribution in the supraoptic, paraventricular, periventricular and arcuate nuclei. CD13-ir increased in the supraoptic nucleus in MSG (2.5-fold) and decreased in the paraventricular nucleus (2-fold) together with FOS-ir (1.5-fold) in FD. In MSG-FD, FOS-ir decreased (7-fold) in the paraventricular nucleus, while CD13-ir decreased in the periventricular (5.6-fold) and the arcuate (3.7-fold) nuclei. It was noteworthy that all these changes of CD13 were not related to catalytic activity of APM. Data suggested that hypothalamic CD13 plays a role in the regulation of energy metabolism not by means of APM enzyme activity.

Agradeço primeiramente a Deus, que me colocou ao encontro de pessoas tão especiais neste mundo e sempre esteve ao meu lado. À minha mãe, Linéia Ruiz Trivilin, que me ensinou o que é caráter, sempre me incentivou a estudar e esteve junto comigo em cada derrota, comemoração, lágrimas e sorrisos nessa jornada chamada vida. Ao meu pai, José Mendes Filho, pelo apoio mesmo sem entender muito bem o que faço, pelo abraço amoroso todas as vezes que o vejo, por sempre me lembrar de Deus e pelos conselhos sempre certos. Ao amor da minha vida Denis Pupo, que não me deixa desistir, aguenta meu mau humor, me faz esquecer as preocupações, é meu companheiro e me lembra sempre que todo o esforço vale a pena por um futuro melhor ao seu lado, por nós. À minha melhor amiga, Camilla de Cássia Sovenhi, por uma amizade maravilhosa de nove anos, por entender minhas ausências, pela companhia inestimável até para ficar sem fazer nada, pelas conversas, risadas, trapalhadas, pelo ombro pra chorar e força sem tamanho. A todos da minha família, irmãs (Anna e Marília), padrasto (Pedro Kobler), tios (Amilton, Luiz), tias (Ligia, Livânia, Rosana), avós (Ana e Agripina), avô (Leonildo) e primos por toda experiência que me é doada, por todo carinho que me é dado e por me apoiarem sempre.

This study aimed to check the involvement of lipid mediator leukotriene (LT) B4 and the activity of LTA4 hydrolase (LTA4H) in the development of arthritis induced in rats by collagen and adjuvant (CIA). High-performance liquid chromatography (HPLC) and enzyme immunoassay (EIA) were used for measurements of LTB4 and LTA4H in plasma, synovial fluid (SF), soluble (SO), and solubilized membrane-bound fraction (MB) from synovial tissue (ST) and peripheral blood mononuclear cells (PBMCs) of CIA-arthritic and CIA-resistant. EIA process is simple, clean, and rapid and offered advantages over HPLC, showing that in SF and MB-PBMCs of CIA-arthritic and CIA-resistant, and in MB-ST of CIA-resistant, LTB4 and LTA4H were altered in parallel and were positively related. In the plasma and SO-ST and SO-PBMCs of CIA-arthritic and CIA-resistant, and in MB-ST of CIA-arthritic, this pattern was not found. The primordial role played by LTA4H in the biosynthesis of LTB4 was confirmed together with the existence of alternative steps that regulate LTB4 without participation of LTA4H. The involvement of compartmentalized and coupled changes of LTB4 and LTA4H in the resistance and development of arthritis in CIA model was demonstrated for the first time.

Rev. Virtual Quim. |Vol 3| |No. 4| |247-274| 247 Artigo δ-Gliconolactona em Síntese Orgânica Reis, M. I. P.; Mendes, M. T.; da Silva, F. C.; Ferreira, V. F.* Rev. Virtual Quim., 2011, 3 (4), 247-274. Data de publicação na Web: 11 de junho de 2011 Abstract: This review will address the importance and the applicability and describes some synthetic routes that use -gluconolactone (DGL) as a starting material for the preparation of other simple derivatives, carbohydrates, gluconamides, heterocycles, small chiral building block and in some total syntheses. ResumoNesta revisão serão abordadas a importância, aplicabilidade e algu as otas si téti as ue utiliza agliconolactona (DGL) como material de partida para a preparação de outros derivados simples, carboidratos, gliconamidas, heterociclos, pequenos blocos quirais e em algumas sínteses totais.

Objective: Previous study demonstrated the involvement of basic aminopeptidase (APB) activity in the development of collagen-induced arthritis (CIA). Two zinc dependent metalloenzymes (EC 3.4.11.6 and EC 3.3.2.6) are known to exhibit concomitantly APB and leukotriene-A4-hydrolase (LT-A4-H) activities. Influence of the interrelationship between both activities on arthritic processes, however, is presently uncertain. This study aimed to compare these activities in CIA. Methods: CIA was induced in rats and arthritis was assessed macroscopically. Ultracentrifugation was used to separate soluble (S) and solubilized membrane-bound (M) fractions from peripheral blood mononuclear cells (PBMCs) and synovial tissue (ST). Enzyme immunoassay was used to measure LT-A4-H activity, and Real Time Polymerase Chain Reaction was used for evaluating EC 3.4.11.6 and EC 3.3.2.6 gene expressions. Results: The existence of genes for EC 3.3.2.6 and EC 3.4.11.6 was demonstrated in the ST. Compared with control, LT-A4-H activity increased in synovial fluid (SF) and in S-PBMCs of CIA-arthritic and CIA-resistant and in M-ST of CIA-resistant, while it decreased in M-PBMCs of CIA-arthritic and CIA-resistant. In all these locations APB activity remained unchanged or inversely correlated with LT-A4-H activity. Conclusions: LT-A4-H and APB activities in joint-related samples are associated, for the first time, with EC 3.3.2.6 and EC 3.4.11.6 genes, exhibiting a compartment-dependent differential modulation of their specificity, efficiency and/or affinity or an inverse concurrent pattern. Changes in LT-A4-H activity have implications for development or resistance to arthritis in CIA model with a potential to be a diagnostic tool.