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‣ Efeitos do resíduo da queima de óleo diesel (ROFA) e da inflamação pulmonar alérgica crônica em três linhagens de camundongos; Effects of residual diesel oil fly ash (ROFA) and pulmonary allergic chronic inflammation in tree lines of mice

Costa, Fernanda Magalhães Arantes
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 09/01/2008 Português
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47.53337%
Neste estudo, foram realizados três experimentos distintos (1) analisando os efeitos da administração de material particulado em camundongos BALB/c com inflamação pulmonar alérgica crônica induzida por ovalbumina; (2) comparando camundongos AIRmax e AIRmin com inflamação pulmonar alérgica crônica induzida por ovalbumina; (3) comparando camundongos AIRmax e AIRmin que receberam material particulado (resíduo da queima de óleo diesel - ROFA) por via intranasal. Para a indução da inflamação pulmonar alérgica crônica, os camundongos foram sensibilizados com ovalbumina (OVA) através de duas injeções intraperitoneais de alérgeno com o adjuvante hidróxido de alumínio (dias 0 e 14) e quatro inalações de OVA 1% (dias 22, 24, 26 e 28). Os animais que foram expostos ao material particulado, receberam ROFA (60 ?g) nos dias 0, 2, 4 e 6 no experimento do efeito do material particulado ou nos dias dos desafios com OVA no experimento do efeito da administração de material particulado em animais com inflamação pulmonar induzida pela OVA. Os grupos controle foram tratados com solução salina 0,9 % seguindo o mesmo protocolo. Quarenta e oito horas após o último desafio, a responsividade pulmonar foi medida por broncoprovocação àr metacolina através da pletismografia de corpo inteiro...

‣ A novel biological activity for galectin-1: Inhibition of leukocyte-endothelial cell interactions in experimental inflammation

La, Mylinh; Cao, Thong V.; Cerchiaro, Graziela; Chilton, Kathya; Hirabayashi, Jun; Kasai, Ken-Ichi; Oliani, Sonia M.; Chernajovsky, Yuti; Perretti, Mauro
Fonte: Universidade Estadual Paulista Publicador: Universidade Estadual Paulista
Tipo: Artigo de Revista Científica Formato: 1505-1515
Português
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Galectin-1 (Gal-1), the prototype of a family of β -galactoside-binding proteins, has been shown to attenuate experimental acute and chronic inflammation. In view of the fact that endothelial cells (ECs), but not human polymorphonuclear leukocytes (PMNs), expressed Gal-1 we tested here the hypothesis that the protein could modulate leukocyte-EC interaction in inflammatory settings. In vitro, human recombinant (hr) Gal-1 inhibited PMN chemotaxis and trans-endothelial migration. These actions were specific as they were absent if Gal-1 was boiled or blocked by neutralizing antiserum. In vivo, hrGal-1 (optimum effect at 0.3 μg equivalent to 20 pmol) inhibited interleukin-1β-induced PMN recruitment into the mouse peritoneal cavity. Intravital microscopy analysis showed that leukocyte flux, but not their rolling velocity, was decreased by an anti-inflammatory dose of hrGal-1. Binding of biotinylated Gal-1 to resting and post-adherent human PMNs occurred at concentrations inhibitory in the chemotaxis and transmigration assays. In addition, the pattern of Gal-1 binding was differentially modulated by PMN or EC activation. In conclusion, these data suggest the existence of a previously unrecognized function of Gal-1, that is inhibition of leukocyte rolling and extravasation in experimental inflammation. It is possible that endogenous Gal-1 may be part of a novel anti-inflammatory loop in which the endothelium is the source of the protein and the migrating PMNs the target for its anti-inflammatory action.

‣ Deleterious effects of low level of vitamin E and high stocking density on the hematology response of pacus, during chronic inflammatory reaction

Andrade Belo, Marco Antonio de; Moraes, Flavio Ruas de; Yoshida, Luciana; Rosa Prado, Ed Johnny da; Engracia de Moraes, Julieta Rodini; Soares, Vando Edesio; Silva, Marta Gomes da
Fonte: Elsevier B.V. Publicador: Elsevier B.V.
Tipo: Artigo de Revista Científica Formato: 124-128
Português
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP); Processo FAPESP: 00/04986-8; The effects of dietary supplementation with 12.6, 58.2 and 310.4 mg of vitamin E/kg dry diet on the hematology response of pacus (Piaractus mesopotamicus), submitted to different stocking densities (5 kg/m(3) and 20 kg/m(3)), were investigated during chronic inflammatory reaction. After a feeding period of 18 weeks, pacu juveniles were anesthetized for inserting round glass coverslips 13 mm in diameter into the subcutaneous connective tissue. 126 fish from 18 groups (i.e., seven fish per aquaria) were sampled for blood collection 2, 7 and 15 days post-implantation to determine levels of plasma cortisol, erythrocyte, thrombocyte and leucocyte counts. In the presence of chronic inflammation, pacus fed with 12.6 mg/kg of vitamin E and kept in high stocking density (20 kg/m(3)) resulted in increased number of circulating red blood cells and hematocrit percentage associated with microcytosis. Thrombocytosis and neutrophilia were observed in the acute phase of pacu defense response. However, it was found that a significant increase in monocyte counts and decrease in thrombocyte, neutrophil and lymphocyte counts in animals were maintained at high stocking density. Pacus fed with 12.6 mg of vitamin E/kg of dry diet presented low number of lymphocytes and LG-PAS+...

‣ Indução do estímulo nociceptivo na região da ATM : mínima concentração efetiva de piperina em condições de normalidade, inflamação local crônica e estresse crônico = Induction of nociceptive stimulus in TMJ region: minimum effective concentration of piperine in normality, local chronic inflammation and chronic stress conditions; Induction of nociceptive stimulus in TMJ region : minimum effective concentration of piperine in normality, local chronic inflammation and chronic stress conditions

Ana Paula Varela Brown Martins
Fonte: Biblioteca Digital da Unicamp Publicador: Biblioteca Digital da Unicamp
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 07/08/2013 Português
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A disfunção temporomandibular pode afetar músculos mastigatórios, articulação temporomandibular (ATM) ou ambos; possui elevada prevalência nas mulheres e sintoma mais comum é a dor. Foi proposto determinar mínima concentração efetiva da piperina para ativar o Potencial Receptor Transiente Vanilóide da subfamília 1 (TRPV1) na região da ATM direita de ratas Wistar, nas condições: normalidade, inflamação crônica na ATM, estresse crônico e associação destas. Foram desenvolvidos 2 estudos experimentais, randomizados, duplo-cegos (protocolo nº 2633-1). No estudo I, 48 animais foram distribuídos aleatoriamente em seis grupos, e cada grupo recebeu 30 μl na ATM de uma das soluções: solução padrão (10% de álcool etílico, 10% de Tween 80 e 80% de solução salina estéril) ou 1, 2, 3, 4 e 5 μg de piperina diluída em 100 ml da solução padrão. No estudo II, 144 ratas foram aleatoriamente distribuídas em grupos: A - inflamação crônica na ATM direita induzida pelo Adjuvante Completo de Freund; B - estresse crônico provocado pelo modelo crônico de estresse; C - associação dessas condições. Esses grupos foram subdivididos (n = 8), e injetados na ATM 30 μl das mesmas soluções descritas previamente. Nos estudos...

‣ Effects of Serenoa Repens, Selenium and Lycopene (Profluss®) on chronic inflammation associated with Benign Prostatic Hyperplasia: results of “FLOG” (Flogosis and Profluss in Prostatic and Genital Disease), a multicentre Italian study

Morgia,Giuseppe; Cimino,Sebastiano; Favilla,Vincenzo; Russo,Giorgio Ivan; Squadrito,Francesco; Mucciardi,Giuseppe; Masieri,Lorenzo; Minutoli,Letteria; Grosso,Giuseppe; Castelli,Tommaso
Fonte: Sociedade Brasileira de Urologia Publicador: Sociedade Brasileira de Urologia
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/04/2013 Português
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Objective To evaluate the efficacy of Profluss® on prostatic chronic inflammation (PCI). Materials and Methods We prospectively enrolled 168 subjects affected by LUTS due to bladder outlet obstruction submitted to 12 cores prostatic biopsy for suspected prostate cancer + 2 cores collected for PCI valuation. First group consisted of 108 subjects, with histological diagnosis of PCI associated with BPH and high grade PIN and/or ASAP, randomly assigned to 1:1 ratio to daily Profluss® (group I) for 6 months or to control group (group Ic). Second group consisted of 60 subjects, with histological diagnosis of BPH, randomly assigned to 1:1 ratio to daily Profluss® + α-blockers treatment (group II) for 3 months or to control group (group IIc). After 6 months first group underwent 24 cores prostatic re-biopsy + 2 cores for PCI while after 3 months second group underwent two-cores prostatic for PCI. Specimens were evaluated for changes in inflammation parameters and for density of T-cells (CD3, CD8), B-cells (CD20) and macrophages (CD68). Results At follow-up there were statistical significant reductions of extension and grading of flogosis, mean values of CD20, CD3, CD68 and mean PSA value in group I compared to Ic, while extension and grading of flogosis in group II were inferior to IIc but not statistical significant. A statistically significant reduction in the density of CD20...

‣ Accumulation of plasma cells in inflamed sites: effects of antigen, nonspecific microbial activators, and chronic inflammation.

Mallison, S M; Smith, J P; Schenkein, H A; Tew, J G
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /11/1991 Português
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Plasma cells are common in chronically inflamed sites, including periodontal lesions. The aim of this study was to determine which factors contribute to this local accumulation of plasma cells. Specifically, we sought to evaluate the effects of specific antigen and nonspecific activators from an infectious agent associated with chronic inflammation (Fusobacterium nucleatum, an organism prominent in chronic periodontal lesions) and the effect of the chronic inflammation itself. Chronic inflammation (14 to 17 days) was induced in horseradish peroxidase (HRP)-immune rabbits by subcutaneous injection of 50 microliters of sterile alum in several sites in their backs. Controls included sites injected with saline or more acute sites examined after 3 days of alum inflammation. Sites were challenged with HRP (the antigen), sonicated F. nucleatum (the nonspecific activator), or both together to see whether F. nucleatum has an adjuvant effect. Three days after challenge, HRP-specific antibody-forming cells (AFC) were enumerated after peroxidase histochemistry. In noninflamed sites or sites with acute inflammation, virtually no HRP-specific AFC were evident. In contrast, chronic inflammation alone was sufficient to elicit a specific AFC response (congruent to 10 cells per mm2). Addition of either F. nucleatum or HRP to the chronic lesion about doubled the number of HRP-specific AFC. However...

‣ Expression of epithelial adhesion proteins and integrins in chronic inflammation.

Haapasalmi, K.; Mäkelä, M.; Oksala, O.; Heino, J.; Yamada, K. M.; Uitto, V. J.; Larjava, H.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /07/1995 Português
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Epithelial cell behavior in chronic inflammation is poorly characterized. During inflammation of tooth-supporting structures (periodontal disease), increased proliferation of epithelial cells into the inflamed connective tissue stroma is commonly seen. In some areas ulceration and degeneration take place. We studied alterations in the expression of adhesion molecules and integrins during chronic periodontal inflammation. In inflamed tissue, laminin-1 and type IV collagen were still present in the basement membrane and surrounding blood vessels, but they were also found extravascularly in inflamed connective tissue stroma. Type VII collagen and laminin-5 (also known as kalinin, epiligrin, or nicein) were poorly preserved in the basement membrane zone, but both were found in unusual streak-like distributions in the subepithelial connective tissue stroma in inflamed tissue. Both fibronectin and tenascin were substantially decreased in chronically inflamed connective tissue, showing only punctate staining at the basement membrane zone. Integrins of the beta 1 family showed two distinct staining patterns in epithelial cells during chronic inflammation; focal losses of beta 1 integrins (alpha 2 beta 1 and alpha 3 beta 1) were found in most areas...

‣ Chronic Inflammation, Colorectal Cancer and Gene Polymorphisms

Boland, C. Richard
Fonte: S. Karger AG Publicador: S. Karger AG
Tipo: Artigo de Revista Científica
Publicado em /11/2010 Português
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Chronic inflammation is commonly present in gastrointestinal mucosal sites at increased risk for cancer, such as in inflammatory bowel disease (IBD) or chronic gastritis caused by Helicobacter pylori infection. Why some patients have more mucosal inflammation than others, and why certain individuals with chronic inflammation develop cancer, are problems that have not been solved. Unlike the case for the syndromic forms of familial colorectal cancer (CRC), the risks for IBD and other forms of chronic inflammation have not been linked to highly penetrant single gene mutations. Single nucleotide polymorphisms (SNP) are variations in DNA sequence that can be linked to any phenotype (cancer, chronic inflammation, etc.) in genome-wide association studies (GWAS). CRC has been linked to several highly penetrant single gene loci, as well as multiple SNP. The propensity to develop IBD has not been linked to single gene mutations in most instances, but has been linked to SNP in the NOD2 locus (which appear to create hypomorphic alleles for this bacterial response gene), the IL23R locus, the autophagy gene ATG16L1 and a wide range of other loci including the Toll-like receptors, JAK2 and STAT3, and perhaps 70 more. At present, the problem in predicting risk for chronic inflammation is that there are many genetic polymorphisms with relatively modest individual effects. Our challenge is to understand how the SNPs that are linked to variations in the inflammatory response interact with one another (i.e. to understand the ‘epistasis’ involved)...

‣ Neutrophils confer T cell resistance to MDSC-mediated suppression to promote chronic inflammation

Ryan, Sean O.; Johnson, Jenny L.; Cobb, Brian A.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Português
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Low-grade chronic inflammation can persist in aging humans unnoticed for years or even decades, inflicting continuous damage that can culminate later in life as organ dysfunction, physical frailty, and some of the most prominent debilitating and deadly age-associated diseases, including rheumatoid arthritis, diabetes, heart disease, and cancer. Despite the near universal acceptance of these associations, the mechanisms underlying unresolved inflammation remain poorly understood. Here we describe a novel inducible method to examine systemic chronic inflammation using susceptible animal models. Induced inflammation results in unresolved innate cellular responses and persistence of the same serum pro-inflammatory molecules used as diagnostic biomarkers and therapeutic targets for chronic inflammation in humans. Surprisingly, we found long-term persistence of an inflammation-associated neutrophil cell population constitutively producing the pro-inflammatory IFNγ cytokine, which until now has only been detected transiently in acute inflammatory responses. Interestingly, these cells appear to confer T cell resistance to the otherwise potent anti-inflammatory function of myeloid-derived suppressor cells (MDSC), revealing a novel mechanism for the maintenance of chronic inflammatory responses over time. This discovery represents an attractive target to resolve inflammation and prevent the inflammation-induced pathologies that are of critical concern for the wellbeing of the aging population.

‣ Violacein Treatment Modulates Acute and Chronic Inflammation through the Suppression of Cytokine Production and Induction of Regulatory T Cells

Verinaud, Liana; Lopes, Stefanie Costa Pinto; Prado, Isabel Cristina Naranjo; Zanucoli, Fábio; Alves da Costa, Thiago; Di Gangi, Rosária; Issayama, Luidy Kazuo; Carvalho, Ana Carolina; Bonfanti, Amanda Pires; Niederauer, Guilherme Francio; Duran, Nelson
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 04/05/2015 Português
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Inflammation is a necessary process to control infection. However, exacerbated inflammation, acute or chronic, promotes deleterious effects in the organism. Violacein (viola), a quorum sensing metabolite from the Gram-negative bacterium Chromobacterium violaceum, has been shown to protect mice from malaria and to have beneficial effects on tumors. However, it is not known whether this drug possesses anti-inflammatory activity. In this study, we investigated whether viola administration is able to reduce acute and chronic autoimmune inflammation. For that purpose, C57BL/6 mice were intraperitoneally injected with 1 μg of LPS and were treated with viola (3.5mg/kg) via i.p. at the same time-point. Three hours later, the levels of inflammatory cytokines in the sera and phenotypical characterization of leukocytes were determined. Mice treated with viola presented a significant reduction in the production of inflammatory cytokines compared with untreated mice. Interestingly, although viola is a compound derived from bacteria, it did not induce inflammation upon administration to naïve mice. To test whether viola would protect mice from an autoimmune inflammation, Experimental Autoimmune Encephalomyelitis (EAE)-inflicted mice were given viola i.p. at disease onset...

‣ Physical Activity Protects the Human Brain against Metabolic Stress Induced by a Postprandial and Chronic Inflammation

Pruimboom, Leo; Raison, Charles L.; Muskiet, Frits A. J.
Fonte: Hindawi Publishing Corporation Publicador: Hindawi Publishing Corporation
Tipo: Artigo de Revista Científica
Português
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47.47232%
In recent years, it has become clear that chronic systemic low-grade inflammation is at the root of many, if not all, typically Western diseases associated with the metabolic syndrome. While much focus has been given to sedentary lifestyle as a cause of chronic inflammation, it is less often appreciated that chronic inflammation may also promote a sedentary lifestyle, which in turn causes chronic inflammation. Given that even minor increases in chronic inflammation reduce brain volume in otherwise healthy individuals, the bidirectional relationship between inflammation and sedentary behaviour may explain why humans have lost brain volume in the last 30,000 years and also intelligence in the last 30 years. We review evidence that lack of physical activity induces chronic low-grade inflammation and, consequently, an energy conflict between the selfish immune system and the selfish brain. Although the notion that increased physical activity would improve health in the modern world is widespread, here we provide a novel perspective on this truism by providing evidence that recovery of normal human behaviour, such as spontaneous physical activity, would calm proinflammatory activity, thereby allocating more energy to the brain and other organs...

‣ Early life socioeconomic adversity is associated in adult life with chronic inflammation, carotid atherosclerosis, poorer lung function and decreased cognitive performance: a crosssectional, population-based study

Packard, Chris J; Bezlyak, Vladimir; McLean, Jennifer S; Batty, David G; Ford, Ian; Burns, Harry; Cavanagh, Jonathan; Deans, Kevin A; Henderson, Marion; McGinty, Agnes; Millar, Keith; Sattar, Naveed; Shiels, Paul G; Nathan, Yoga; Tannahill, Carol
Fonte: BioMed Central Ltd. Publicador: BioMed Central Ltd.
Tipo: info:eu-repo/semantics/article; all_ul_research; ul_published_reviewed
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peer-reviewed; Background: Socioeconomic gradients in health persist despite public health campaigns and improvements in healthcare. The Psychosocial and Biological Determinants of Ill-health (pSoBid) study was designed to uncover novel biomarkers of chronic disease that may help explain pathways between socioeconomic adversity and poorer physical and mental health. Methods: We examined links between indicators of early life adversity, possible intermediary phenotypes, and markers of ill health in adult subjects (n = 666) recruited from affluent and deprived areas. Classical and novel risk factors for chronic disease (lung function and atherosclerosis) and for cognitive performance were assessed, and associations sought with early life variables including conditions in the parental home, family size and leg length. Results: Associations were observed between father’s occupation, childhood home status (owner-occupier; overcrowding) and biomarkers of chronic inflammation and endothelial activation in adults (C reactive protein, interleukin 6, intercellular adhesion molecule; P < 0.0001) but not number of siblings and leg length. Lung function (forced expiratory volume in 1 second) and cognition (Choice Reaction Time, the Stroop test...

‣ Emerging and future therapies for the treatment of bone loss associated with chronic inflammation

Haynes, D.
Fonte: Kluwer Academic Publ Publicador: Kluwer Academic Publ
Tipo: Artigo de Revista Científica
Publicado em //2006 Português
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67.1208%
Currently there are many emerging therapies for the treatment of chronic osteoporosis. This is a major problem world wide and particularly of concern in post-menopausal women. This has offered a large expanding market for the pharmaceutical industry and consequently large amounts of money and resources have been used to develop new treatments. These new and emerging treatments have largely targeted the mechanisms of bone loss associated with post-menopausal osteoporosis. However, there are many other important bone loss disorders and it is possible that some of these new therapies may be useful in treating bone loss associated with other diseases. This review identifies several of these pharmacologic treatments of osteoporosis and discusses the possibility of using these drugs for the treatment of bone loss associated with inflammatory diseases. In addition, other approaches, such as regulating apoptosis and intracellular signalling, may be developed in the future and may better target bone loss associated with chronic inflammation are identified.; D. R. Haynes; © Springer

‣ The effect of azithromycin on acute and chronic inflammation in an in vivo experimental model.

Du Bois, A. H.
Fonte: Universidade de Adelaide Publicador: Universidade de Adelaide
Tipo: Tese de Doutorado
Publicado em //2013 Português
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Background: Macrolide antibiotics have been found to have both antimicrobial and antiinflammatory properties. They may be useful adjuncts in the treatment of conditions in which both these factors play a role, such as periodontitis. Objectives: The aim of this study was to evaluate the effect of azithromycin in a rat model of experimentally induced acute and chronic inflammation. Material and methods: Polyurethane sponges loaded with either heat killed Porphyromonas gingivalis (HKPG), Mycobacterium tuberculosis (HKTB) or Phosphate Buffered Saline (PBS) were surgically implanted into the fore flanks of rats. To determine any acute inflammatory effects animals received azithromycin 4 days prior to surgery, while to determine the effects on chronic inflammation animals did not receive azithromycin until day 25 post operatively. The control groups did not receive azithromycin. The sponges were retrieved at days 7, 14, 21, 35 and 49, wet weights recorded and then processed for histological evaluation of acute and chronic inflammation and fibrosis. Additionally, immunohistochemical staining was used to identify macrophages using CD163 and CD68 macrophage markers at days 21 and 35. Biochemical analyses were used to determine serum levels of C-reactive protein (CRP) and hydroxyproline (HP) content in the retrieved sponges. Results: No differences were found between wet and dry weights of sponges for any of the groups. Acute Inflammation: A trend for lower inflammation and infiltration scores was observed for all azithromycin treated groups compared to untreated groups...

‣ Chronic Inflammation of the Oral Cavity and Squamous Cell DNA Methylation; Chronische Entzündung der Mundhöhle und DNA Methylierung des Plattenepithels

Gasche, Jacqueline Anke Katja
Fonte: Universidade de Tubinga Publicador: Universidade de Tubinga
Tipo: Dissertação
Português
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Introduction: Worldwide oral squamous cell carcinoma (OSCC) accounts for more than 100,000 deaths per year. Chronic inflammation is considered one of its risk factors. DNA methylation may regulate gene expression and contribute to OSCC tumorigenesis. This project investigated whether chronic inflammation alters DNA methylation and expression of cancer-associated genes in OSCC. Methods: Several in-vitro models of chronic inflammation were established. Co-culture with activated neutrophils, oxidative or nitrosative stress, and interleukin (IL)-6 were tested for methylation pattern changes in OSCC cell lines. The methylation status was analyzed by pyrosequencing, methylation-specific multiplex ligation-dependent probe amplification, and sensitive melting analysis after methylation-specific PCR. Gene expression was investigated by qRT-PCR. DNA methyltransferase (DNMT)-1 and DNMT3b expression was assessed by western blot. Results: All three inflammatory models induced LINE-1 demethylation which can be interpreted as global DNA hypomethylation. CpG promoter methylation changes were observed in several tumor suppressor genes upon IL-6 treatment. In detail, CHFR, GATA5, and PAX6 altered gene expression upon change in CpG methylation. The western blot did not detect any increase in DNMT1 and DNMT3b. Conclusion: Our results indicate that chronic inflammation contributes to tumorigenesis in-vitro by altering gene methylation and consequently their expression independent of DNMT protein expression. Epigenetic gene silencing may be the consequence of chronic inflammation in the oral cavity. Both methylation and inflammation are suitable targets for developing novel preventive measures.; Einleitung: Das Plattenepithelkarzinom der Mundhöhle fordert weltweit 100.000 Todesfälle pro Jahr. Chronische Entzündung gilt als einer der Risikofaktoren. Als epigenetischer Prozess reguliert DNA Methylierung vermutlich die Genexpression und ist damit an der Tumorentstehung beteiligt. Dieses Projekt erforscht...

‣ THE ROLE OF NERVE GROWTH FACTOR DURING CHRONIC INFLAMMATION OF THE DESCENDING COLON IN VIVO: A NOVEL SOURCE FOR NERVE GROWTH FACTOR

Petrie, Casey
Fonte: Quens University Publicador: Quens University
Tipo: Tese de Doutorado
Português
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In these experiments, we primarily investigate the role and source of nerve growth factor (NGF) in peripheral tissues undergoing chronic inflammation. It has been previously determined that there is a significant increase in the levels of NGF following prolonged inflammation of the urinary bladder or the colon, and the first of two projects discussed here mimics this increase with transgenic mice which ectopically produce NGF under control of the smooth muscle alpha-actin promoter. It was determined by this increase that a p75-sensitive increase in sympathetic innervation occurs when an abundance of NGF is produced locally in the descending colon. Sensory innervation in the colon was found to come from two unique populations, one of which increased following heightened NGF levels. The urinary bladders of NGF overexpressing mice were determined to have an increase in sensory axonal density. The second project described here features chemically induced colonic inflammation and observes the nervous and growth factor changes as a response. Transgenic reporter mice are used to observe the cellular source of NGF in the descending colon, which unexpectedly was determined to be Dogiel type II (DgII neurons) based on morphological and chemical characteristics. We report the increase in NGF mRNA and protein observed following a brief 5-day colonic inflammation...

‣ Rho-kinase inhibition attenuates airway responsiveness, inflammation, matrix remodeling, and oxidative stress activation induced by chronic inflammation

Possa, Samantha Souza; Charafeddine, Homar Toledo; Righetti, Renato Fraga; Silva, Patricia Angeli da; Almeida-Reis, Rafael; Saraiva-Romanholo, Beatriz Mangueira; Perini, Adenir; Prado, Carla Maximo; Leick-Maldonado, Edna Aparecida; Martins, Milton A.; Lop
Fonte: AMER PHYSIOLOGICAL SOC; BETHESDA Publicador: AMER PHYSIOLOGICAL SOC; BETHESDA
Tipo: Artigo de Revista Científica
Português
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Possa SS, Charafeddine HT, Righetti RF, da Silva PA, Almeida-Reis R, Saraiva-Romanholo BM, Perini A, Prado CM, Leick-Maldonado EA, Martins MA, Tiberio ID. Rho-kinase inhibition attenuates airway responsiveness, inflammation, matrix remodeling, and oxidative stress activation induced by chronic inflammation. Am J Physiol Lung Cell Mol Physiol 303: L939-L952, 2012. First published September 21, 2012; doi:10.1152/ajplung.00034.2012.-Several studies have demonstrated the importance of Rho-kinase in the modulation of smooth muscle contraction, airway hyperresponsiveness, and inflammation. However, the effects of repeated treatment with a specific inhibitor of this pathway have not been previously investigated. We evaluated the effects of repeated treatment with Y-27632, a highly selective Rho-kinase inhibitor, on airway hyperresponsiveness, oxidative stress activation, extracellular matrix remodeling, eosinophilic inflammation, and cytokine expression in an animal model of chronic airway inflammation. Guinea pigs were subjected to seven ovalbumin or saline exposures. The treatment with Y-27632 (1 mM) started at the fifth inhalation. Seventy-two hours after the seventh inhalation, the animals' pulmonary mechanics were evaluated, and exhaled nitric oxide (E-NO) was collected. The lungs were removed...

‣ Chronic inflammation: a failure of resolution?

Lawrence, Toby; Gilroy, Derek W
Fonte: Blackwell Science Inc Publicador: Blackwell Science Inc
Tipo: Artigo de Revista Científica
Publicado em /04/2007 Português
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Inflammation has evolved as a protective response to insult or injury, it's a primordial response that eliminates or neutralises foreign organisms or material, the resolution of inflammation encompasses the endogenous anti-inflammatory mechanisms that protect us against excessive tissue injury and promote the restoration of tissue structure and function. In fact, our well being and survival depends upon its efficiency and carefully-balanced control. In general, the innate inflammatory response initiates within minutes and, if all is well, resolves within hours. In contrast, chronic inflammation persists for weeks, months or even years. Here, we are going to discuss the key endogenous checkpoints necessary for mounting an effective yet limited inflammatory response and the crucial biochemical pathways necessary to prevent its persistence.

‣ Radiolabelled cytokines for imaging chronic inflammation

Signore,Alberto; D'Alessandria,Calogero; Annovazzi,Alessio; Scopinaro,Francesco
Fonte: Instituto de Tecnologia do Paraná - Tecpar Publicador: Instituto de Tecnologia do Paraná - Tecpar
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/09/2002 Português
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Diagnosis and particularly follow-up of chronic inflammatory disorders could be often difficult in clinical practice. Indeed, traditional radiological techniques reveal only structural tissue alterations and are not able to monitor functional changes occurring in tissues affected by chronic inflammation. The continuous advances in the knowledge of the pathophysioloy of chronic disorders, combined with the progress of radiochemistry, led to the development of new specific radiolabelled agents for the imaging of chronic diseases. In this scenario, cytokines, due to their pivotal role in such diseases, represent good candidates as radiopharmaceuticals.

‣ Dissociation of inflammatory and epithelial responses in a murine model of chronic asthma

Foster, Paul S; Yang, Ming; Matthaei, Klaus; Young, I M; Temelkovski, J; Kumar, Rakesh K
Fonte: Lippincott Williams & Wilkins Publicador: Lippincott Williams & Wilkins
Tipo: Artigo de Revista Científica
Português
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To study pathogenetic mechanisms in chronic asthma, we employed a novel experimental model that replicates characteristic features of the human disease. Chronic inflammation and epithelial changes, specifically localized to the airways, were induced by repeated exposure of systemically sensitized BALB/c mice to low mass concentrations of aerosolized ovalbumin for 6 weeks. The contribution of Th2 cytokine-driven inflammation to the development of airway lesions and hyperreactivity was assessed in cytokine-deficient mice. In interleukin-5-deficient animals, intraepithelial eosinophils and chronic inflammatory cells in the lamina propria of the airways were markedly decreased; however, these animals developed epithelial hypertrophy and subepithelial fibrosis comparable with that observed in sensitized wild type mice. Airway hyperreactivity to inhaled methacholine did not develop in interleukin-5-deficient mice. In contrast, interleukin-4-deficient mice exhibited no decrease in airway inflammation, but had significantly greater epithelial hypertrophy and subepithelial fibrosis, as well as exaggerated hyperreactivity to methacholine. We conclude that interleukin-5, but not interleukin-4, plays a central role in the development of chronic inflammation of the airways and the induction of airway hyperreactivity. Furthermore...