Myeloid-related proteins 8 and 14 contribute to monosodium urate monohydrate crystal-induced inflammation in gout.

OBJECTIVE: Monosodium urate monohydrate (MSU) crystal-induced interleukin-1β (IL-1β) secretion is a critical factor in the pathogenesis of gout. However, without costimulation by a proIL-1β-inducing factor, MSU crystals alone are insufficient to induce IL-1β secretion. The responsible costimulatory factors that act as a priming endogenous signal in vivo are not yet known. We undertook this study to analyze the costimulatory properties of myeloid-related protein 8 (MRP-8) and MRP-14 (endogenous Toll-like receptor 4 [TLR-4] agonists) in MSU crystal-induced IL-1β secretion and their relevance in gout. METHODS: MRP-8/MRP-14 was measured in paired serum and synovial fluid samples by enzyme-linked immunosorbent assay (ELISA) and localized in synovial tissue from gout patients by immunohistochemistry. Serum levels were correlated with disease activity, and MSU crystal-induced release of MRPs from human phagocytes was measured. Costimulatory effects of MRP-8 and MRP-14 on MSU crystal-induced IL-1β secretion from phagocytes were analyzed in vitro by ELISA, Western blotting, and polymerase chain reaction. The impact of MRP was tested in vivo in a murine MSU crystal-induced peritonitis model. RESULTS: MRP-8/MRP-14 levels were elevated in the synovium, tophi, and serum of patients with gout and correlated with disease activity. MRP-8/MRP-14 was released by MSU crystal-activated phagocytes and increased MSU crystal-induced IL-1β secretion in a TLR-4-dependent manner. Targeted deletion of MRP-14 in mice led to a moderately reduced response of MSU crystal-induced inflammation in vivo. CONCLUSION: MRP-8 and MRP-14, which are highly expressed in gout, are enhancers of MSU crystal-induced IL-1β secretion in vitro and in vivo. These endogenous TLR-4 ligands released by activated phagocytes contribute to the maintenance of inflammation in gout.

The experimental granuloma: a hypothesis to explain the persistence of the lesion

Granulomatous inflammation is the morphological substrate of a variety of important infectious diseases such as tuberculosis, leprosy, schistosomiasis and others. Nevertheless, although many aspects of this special type of inflammation are known, fundamental questions concerning granuloma formation, persistence, fate and significance for host-parasite relationships still remain to be elucidated. In this brief review, the basic and more relevant literature related to experimental investigations on granuloma physiopathology is presented. Based on recent investigations performed in our laboratory showing that MDF (Macrophage Deactivating Fator) secreted by epithelioid cells and characterized as the calcium-binding protein protein MRP-14 deactivates activated macrophages, a hypothesis to explain the persistence of granulomatous inflammation is put forward

Macrophage suppression following phagocytosis of apoptotic neutrophils is mediated by the S100A9 calcium-binding protein

The clearance of apoptotic cells by phagocytes is a fundamental process during tissue remodeling and resolution of inflammation. In turn, the phagocytosis of apoptotic cells generates signals that suppress pro-inflammatory activation of macrophages. These events occur during the resolution phase of inflammation and therefore the malfunctioning of this process may lead to inflammation-related tissue damage. Here, we demonstrate that the calcium-binding protein S100A9, normally abundant in the cytoplasm of neutrophils and also released by apoptotic neutrophils, is involved in the suppression of macrophages after the uptake of apoptotic neutrophils. Both, spontaneous and induced production of inflammatory species (nitric oxide, hydrogen peroxide and TNF-alpha) as well as the phagocytic activity were inhibited when macrophages were in presence of apoptotic neutrophils, conditioned medium from neutrophil cultures or a peptide corresponding to the C-terminal region of S100A9 protein. On the other hand, macrophages kept in the conditioned medium of neutrophils that was previously depleted of S100A9 were shown to resume the activated status. Finally, we demonstrate that the calcium-binding property of S100A9 might play a role in the suppression process, since the stimulation of intracellular calcium release with ionomycin significantly reversed the effects of the uptake of apoptotic neutrophils in macrophages. In conclusion, we propose that S100A9 is a novel component of the regulatory mechanisms of inflammation, acting side-by-side with other suppressor factors generated upon ingestion of apoptotic cells. (C) 2009 Elsevier GmbH. All rights reserved.

Involvement of proteinase-activated receptors 1 and 2 in spreading and phagocytosis by murine adherent peritoneal cells: Modulation by the C-terminal of S100A9 protein

Proteinase-activated receptors (PAR) are widely recognized for their modulatory properties in inflammatory and immune responses; however, their direct role on phagocyte effector functions remains unknown. S100A9, a protein secreted during inflammatory responses, deactivates activated peritoneal macrophages, and its C-terminal portion inhibits spreading and phagocytosis of adherent peritoneal cells. Herein, the effect of PAR1 and PAR2 agonists was investigated on spreading and phagocytosis by adherent peritoneal cells, as well as the ability of murine C-terminal of S100A9 peptide (mS100A9p) to modulate this effect. Adherent peritoneal cells obtained from mouse abdominal cavity were incubated with PAR1 and PAR2 agonists and spreading and phagocytosis of Candida albicans particles were evaluated. PAR1 agonists increased both the spreading and the phagocytic activity, but PAR2 agonists only increased the spreading index. mS100A9p reverted both the increased spreading and phagocytosis induced by PAR1 agonists, but no interference in the increased spreading induced by PAR2 agonists was noticed. The shorter homologue peptide to the C-terminal of mS100A9p, corresponding to the H(92)-E(97) region, also reverted the increased spreading and phagocytosis induced by PAR1 agonists. These findings show that proteinase-activated receptors have an important role for spreading and phagocytosis of adherent peritoneal cells, and that the pepticle corresponding to the C-terminal of S100A9 protein is a remarkable candidate for use as a novel compound to modulate PAR1 function. (C) 2009 Elsevier B.V. All rights reserved.

Validation of Relapse Risk Biomarkers for Routine Use in Patients With Juvenile Idiopathic Arthritis

Objective. The myeloid-related proteins 8 and 14 (MRP-8/MRP-14) and neutrophil-derived S100A12 are biomarkers of inflammation. They can be used to determine the relapse risk in patients with juvenile idiopathic arthritis (JIA) after stopping antiinflammatory treatment. In this study, we tested the performance of different enzyme-linked immunosorbent assays (ELISAs) in order to validate systems available for routine use.Methods. MRP-8/MRP-14 and S100A12 serum concentrations of 188 JIA patients in remission were analyzed. Commercially available test systems were compared to experimental ELISAs established in house. The ability of the assays to identify JIA patients at risk for relapse was analyzed.Results. For MRP-8/MRP-14, the PhiCal Calprotectin and Buhlmann MRP8/14 Calprotectin ELISAs revealed hazard ratios of 2.3 and 2.1, respectively. For S100A12, the CircuLex S100A12/EN-RAGE ELISA revealed a hazard ratio of 3.1. The commercial assays allowed a JIA relapse prediction that was at least comparable to the experimental ELISAs.Conclusion. For the prediction of JIA relapse after stopping medication, the biomarkers MRP-8/MRP-14 and S100A12 can be determined by using assays that are available for routine use. The tested commercial MRP-8/MRP-14 and S100A12 ELISAs showed a performance comparable to well-established experimental ELISA protocols when assay-specific cutoffs for the indication of relapse prediction are thoroughly applied.

15-deoxy-Δ12,14-prostaglandin J2 Reduces Albumin-induced Arthritis In Temporomandibular Joint Of Rats.

The aim of this study was to evaluate the peripheral effect of 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) in albumin-induced arthritis in temporomandibular joint (TMJ) of rats. Antigen-induced arthritis (AIA) was generated in rats with methylated bovine serum albumin (mBSA) diluted in complete Freund׳s adjuvant. Pretreatment with an intra-articular injection of 15d-PGJ2 (100 ng/TMJ) before mBSA intra-articular injection (10 µg/TMJ) (challenge) in immunized rats significantly reduced the albumin-induced arthritis inflammation. The results demonstrated that 15d-PGJ2 was able to inhibit plasma extravasation, leukocyte migration and the release of inflammatory cytokines IL-6, IL-12, IL-18 and the chemokine CINC-1 in the TMJ tissues. In addition, 15d-PGJ2 was able to increase the expression of the anti-adhesive molecule CD55 and the anti-inflammatory cytokine IL-10. Taken together, it is possible to suggest that 15d-PGJ2 inhibit leukocyte infiltration and subsequently inflammatory process, through a shift in the balance of the pro- and anti-adhesive properties. Thus, 15d-PGJ2 might be used as a potential anti-inflammatory drug to treat arthritis-induced inflammation of the temporomandibular joint.

Analysis Of The Ergosterol Biosynthesis Pathway Cloning, Molecular Characterization And Phylogeny Of Lanosterol 14 α-demethylase (erg11) Gene Of Moniliophthora Perniciosa.

The phytopathogenic fungus Moniliophthora perniciosa (Stahel) Aime & Philips-Mora, causal agent of witches' broom disease of cocoa, causes countless damage to cocoa production in Brazil. Molecular studies have attempted to identify genes that play important roles in fungal survival and virulence. In this study, sequences deposited in the M. perniciosa Genome Sequencing Project database were analyzed to identify potential biological targets. For the first time, the ergosterol biosynthetic pathway in M. perniciosa was studied and the lanosterol 14α-demethylase gene (ERG11) that encodes the main enzyme of this pathway and is a target for fungicides was cloned, characterized molecularly and its phylogeny analyzed. ERG11 genomic DNA and cDNA were characterized and sequence analysis of the ERG11 protein identified highly conserved domains typical of this enzyme, such as SRS1, SRS4, EXXR and the heme-binding region (HBR). Comparison of the protein sequences and phylogenetic analysis revealed that the M. perniciosa enzyme was most closely related to that of Coprinopsis cinerea.

Crescimento, composição corporal e performance motora em crianças e adolescentes de 7 a 14 anos provenientes de familias de baixo nivel socio-economico e participantes do projeto esporte solidario, São Luis - MA

Universidade Estadual de Campinas . Faculdade de Educação Física

Estudo das alterações morfologicas do sistema locomotor em escolares do ensino fundamental : faixa etaria entre 7 e 14 anos de ambos os sexos do municipio de Marechal Candido Rondon, PR - através da avaliação computadorizada

Universidade Estadual de Campinas. Faculdade de Educação Física

Indicadores de tendencia secular de variaveis associadas ao crescimento, a composição corporal e ao desempenho motor de crianças de 7 a 14 anos

Universidade Estadual de Campinas . Faculdade de Educação Física

"Crescimento humano, composição corporal e desenvolvimento das caracteristicas sexuais secundarias de adolescentes de 11 a 14 anos"

Universidade Estadual de Campinas . Faculdade de Educação Física

Prevalência e severidade de gengivite em escolares de 7 a 14 anos: condições locais associadas ao sangramento à sondagem

O objetivo deste estudo foi coletar dados sobre a prevalência e severidade de gengivite em uma amostra de crianças em idade escolar, bem como sua relação com possíveis fatores de risco locais. Duzentos e seis indivíduos foram examinados, sendo 107 meninos e 99 meninas, com idades entre 7 e 14 anos; foram coletados dados referentes ao índice de placa (IP), índice gengival (IG) e profundidade clínica de sondagem (PCS). Entre os parâmetros clínicos observados, as médias referentes a PCS, IP e IG encontradas foram de 1,58 + 0,46, 1,12 + 0,49 e 0,89 + 0,32, respectivamente. Noventa e cinco indivíduos (46,1%) apresentaram um quadro de gengivite leve e 111 (53,9%), de gengivite moderada. No geral, os indivíduos do sexo masculino apresentaram estatisticamente maior quantidade de placa bacteriana e maior inflamação do tecido gengival que indivíduos do sexo feminino. A presença de inflamação gengival foi encontrada em todos os indivíduos examinados. A severidade de inflamação nos dentes permanentes esteve diretamente relacionada à quantidade de placa e ao sangramento à sondagem.

Synteny of human chromosomes 14 and 15 in the platyrrhines (Primates, Platyrrhini)

In order to study the intra- and interspecific variability of the 14/15 association in Platyrrhini, we analyzed 15 species from 13 genera, including species that had not been described yet. The DNA libraries of human chromosomes 14 and 15 were hybridized to metaphases of Alouatta guariba clamitans, A. caraya, A. sara, Ateles paniscus chamek, Lagothrix lagothricha, Brachyteles arachnoides, Saguinus midas midas, Leontopithecus chrysomelas, Callimico goeldii, Callithrix sp., Cebus apella, Aotus nigriceps, Cacajao melanocephalus, Chiropotes satanas and Callicebus caligatus. The 14/15 hybridization pattern was present in 13 species, but not in Alouatta sara that showed a 14/15/14 pattern and Aotus nigriceps that showed a 15/14/15/14 pattern. In the majority of the species, the HSA 14 homologue retained synteny for the entire chromosome, whereas the HSA 15 homologue displayed fragmented segments. Within primates, the New World monkeys represent the taxon with the highest variability in chromosome number (2n = 16 to 62). The presence of the HSA 14/15 association in all species and subspecies studied herein confirms that this association is the ancestral condition for platyrrhines and that this association has been retained in most platyrrhines, despite the occurrence of extensive inter- and intrachromosomal rearrangements in this infraorder of Primates.

Associação entre o índice de massa corporal de pais e de escolares de 7 a 14 anos de Florianópolis, SC, Brasil

OBJETIVOS: verificar a associação entre o Índice de Massa Corporal (IMC) de escolares de 7 a 14 anos e dos respectivos pais. MÉTODOS: estudo transversal com 886 escolares de quatro escolas de Florianópolis, SC. Diagnóstico antropométrico dos escolares e dos pais definido, respectivamente, a partir do IMC para idade de acordo com Centers for Disease Control and Prevention e dos pontos de corte da Organização Mundial da Saúde. A associação entre o IMC dos pais e dos escolares foi estimada por meio da razão de prevalência (RP) com intervalo de confiança (IC) de 95% e teste qui-quadrado com valor de significância de p< 0,05. RESULTADOS: identificou-se prevalência de sobrepeso/obesidade mais elevada em meninos (29,9%) quando comparada a de meninas (17,7%) (p<0,001). Observou-se relação estatisticamente significante entre o IMC de escolares do sexo feminino com o IMC das mães (RP=1,63; IC95%=1,1-3,0; p=0,02) e dos pais (RP=1,78; IC95%= 1,1-3,5; p=0,01). Nos escolares do sexo masculino a associação observada não foi estatisticamente significante. CONCLUSÕES: identificou-se que a prevalência do sobrepeso ou obesidade é 1,63 vezes maior, entre as meninas, quando a mãe também apresenta esse distúrbio e 1,78 vezes maior quando o pai o apresenta, em comparação a mães e pais eutróficos ou de baixo peso.