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Chronic Inflammatory Disease (chronic + inflammatory_disease)
Selected AbstractsA systems biology approach to understanding atherosclerosisEMBO MOLECULAR MEDICINE, Issue 3 2010Stephen A. Ramsey Abstract Atherosclerosis, a chronic inflammatory disease of the vascular system, presents significant challenges to developing effective molecular diagnostics and novel therapies. A systems biology approach integrating data from large-scale measurements (e.g. transcriptomics, proteomics and genomics) is successfully contributing to deciphering regulatory networks underlying the response of many different cellular systems to perturbations. Such a network analysis strategy using pathway information and data from multiple measurement platforms, tissues and species is a promising approach to elucidate the mechanistic underpinnings of complex diseases. Here, we present our views on the contributions that a systems approach can bring to the study of atherosclerosis, propose ways to tackle the complexity of the disease in a systems manner and review recent systems-level studies of the disease. [source] Epidemiologic issues in studies of association between apical periodontitis and systemic healthENDODONTIC TOPICS, Issue 1 2004Daniel J. Caplan Perhaps the most exciting issue currently facing the dental research community centers around a hypothesized connection between chronic inflammatory oral infections, most notably periodontal disease, and the development of adverse systemic health conditions. To date, inflammation of endodontic origin (i.e., apical periodontitis (AP)) has not been extensively studied in this regard despite being a commonly found sequel to bacterial infection of the dental pulp space. Although numerous differences exist between chronic inflammatory disease of periodontal and endodontic origins, there are some notable similarities, primarily that: (1) both often are associated with Gram-negative anaerobic bacteria, and (2) elevated cytokine levels may be released systemically from acute and chronic manifestations of both disease processes. This article provides a brief review of several important concepts concerning adverse general health outcomes as they relate to periodontal disease, summarizes recent epidemiologic studies of AP and root canal therapy, and reviews some general issues involved in the conduct of epidemiologic studies as well as how these issues apply to investigations that address potential links between endodontic inflammatory disease and adverse systemic health outcomes. [source] A pseudosymmetric cell adhesion regulatory domain in the ,7 tail of the integrin ,4,7 that interacts with focal adhesion kinase and srcEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 8 2006Geoffrey Abstract The ,7 integrins ,4,7 and ,E,7 play key roles in forming the gut-associated lymphoid tissue, and contribute to chronic inflammation. The ,4,7 integrin-mediated adhesion of activated lymphocytes is largely due to a transient increase in avidity from ligand-induced clustering of ,4,7 at the cell-surface. Here, we report that L and D enantiomers of a cell-permeable peptide YDRREY encompassing residues 735,740 of the cytoplasmic tail of the ,7 subunit inhibit the adhesion of T cells to ,7 integrin ligands. The YDRREY peptide abrogated mucosal addressin cell adhesion molecule-1-induced clustering of ,4,7 on the surface of activated T cells. A mutated form of the YDRREY peptide carrying either single or double conservative mutations at Tyr735Phe and Tyr740Phe was unable to inhibit T cell adhesion, suggesting that both tandem tyrosines are critical for activity. The YDRREY peptide was bound and phosphorylated by focal adhesion kinase and src, which may serve to sequester cytoskeletal proteins to the cytoplasmic domain of ,4,7. The quasi-palindromic sequence YDRREY within the ,7 cytoplasmic tail constitutes a cell adhesion regulatory domain that modulates the interaction of ,7-expressing leukocytes with their endothelial and epithelial ligands. Cell-permeable peptidomimetics based on this motif have utility as anti-inflammatory reagents for the treatment of chronic inflammatory disease. [source] Chlamydia pneumoniae infections prevent the programmed cell death on THP-1 cell lineFEMS MICROBIOLOGY LETTERS, Issue 1 2002C.Romano Carratelli Abstract Chlamydia pneumoniae is an obligate intracellular bacterium which frequently causes airway infection in humans and has been implicated in chronic inflammatory disease and atherosclerosis. Here we show that infection with C. pneumoniae protects THP-1 cells against the apoptosis which spontaneously occurs in macrophages in the absence of an activation signal. Analysis by flow cytometry at different post-infection times revealed that 50±7% of THP-1 cells were apoptotic at 48 h after onset of the experiments, whereas C. pneumoniae -infected cultures (multiplicity of infection, MOI = 30) displayed only 18±4% of cells in apoptosis. At MOI = 20 and MOI = 10 the cells susceptible to apoptosis at 48 h were 28±5% and 35±6% respectively. Moreover, the results show that heat-inactivated bacteria do not give significant protection against apoptosis, even at higher MOI (MOI = 30), while UV-treated Chlamydia did provide a degree of protection against apoptosis. These data suggest that the anti-apoptotic effect of C. pneumoniae requires a heat-labile component released during infection, and that the effect is not lipopolysaccharide-dependent. [source] Interleukin-6 (G-174C) and tumour necrosis factor-alpha (G-308A) gene polymorphisms in geriatric patients with chronic periodontitisGERODONTOLOGY, Issue 1 2010A. M. Costa doi:10.1111/j.1741-2358.2009.00291.x Interleukin-6 (G-174C) and tumour necrosis factor-alpha (G-308A) gene polymorphisms in geriatric patients with chronic periodontitis Background and objective:, Periodontitis is a chronic inflammatory disease, and genetic factors may have an important role in its severity. Polymorphisms in the promoter regions of the interleukin-6 (IL-6) and tumour necrosis factor-, (TNF-,) genes have been reported to cause changes in the production of these cytokines. The aim of this study was to evaluate the possible role of IL-6 (G,174C) and tumour necrosis factor (G,308A) polymorphisms, in the severity of chronic periodontitis in an elderly population. Materials and methods:, In this study, a group of 65 elderly women, comprising 17 patients with moderate chronic periodontitis, 21 with severe chronic periodontitis and 27 healthy patients were selected. DNA was isolated from all subjects, and polymerase chain reaction was used to study the IL-6 and TNF-, gene polymorphisms. Results:, The results of this study showed a significant difference in the allele and genotype frequencies of IL-6 gene polymorphism between patients with periodontal disease and controls. Subjects carrying the G/G genotype of IL-6 were most severely affected by periodontitis. The TNF-, gene polymorphism showed no association with chronic periodontitis between patients and controls. Conclusion:, The results suggest that the IL-6 gene polymorphism may be associated with chronic periodontitis, and that TNF-, gene polymorphism may not be involved in the progression of chronic periodontitis in the population of elderly Brazilian women. [source] Suppression of allergic airway inflammation in a mouse model by Der p2 recombined BCGIMMUNOLOGY, Issue 1pt2 2009Hai-Feng Ou-Yang Summary Allergic asthma is a chronic inflammatory disease mediated by T helper (Th)2 cell immune responses. Currently, immunotherapies based on both immune deviation and immune suppression, including the development of recombinant mycobacteria as immunoregulatory vaccines, are attractive treatment strategies for asthma. In our previous studies, we created a genetically recombinant form of bacille Calmette,Guerin (rBCG) that expressed Der p2 of house dust mites and established that it induced a shift from a Th2 response to a Th1 response in naive mice. However, it is unclear whether rBCG could suppress allergic airway inflammation in a mouse model. In this article we report that rBCG dramatically inhibited airway inflammation, eosinophilia, mucus production and mast cell degranulation in allergic mice. Analysis of interferon-, (IFN-,) and interleukin-4 (IL-4) levels in bronchoalveolar lavage fluid (BALF) and lung tissue revealed that the suppression was associated with a shift from a Th2 response to a Th1 response. At the same time, rBCG induced a CD4+ CD25+ Foxp3+ T-cell subtype that could suppress the proliferation of Th2 effector cells in vitro in an antigen-specific manner. Moreover, suppression of CD4+ CD25+ T cells could be adoptively transferred. Thus, our results demonstrate that rBCG induces both generic and specific immune responses. The generic immune response is associated with a shift from a Th2 to a Th1 cytokine response, whereas the specific immune response against Der p2 appears to be related to the expansion of transforming growth factor-, (TGF-,)-producing CD4+ CD25+ Foxp3+ regulatory T cells. rBCG can suppress asthmatic airway inflammation through both immune deviation and immune suppression and may be a feasible, efficient immunotherapy for asthma. [source] Anti tumour necrosis-, therapy increases the number of FOXP3+ regulatory T cells in children affected by Crohn's diseaseIMMUNOLOGY, Issue 2 2008Ida Ricciardelli Summary Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract. Its pathogenesis is not completely understood, though the prevailing model is that the intestinal flora drives a strong intestinal T helper 1 (Th1)/Th17 type immune response and inflammation in the genetically susceptible host. This leads to overly aggressive T-cell responses to normal bacteria causing tissue damage. Intestinal homeostasis and maintenance of tolerance to harmless antigens in the intestine has been shown to be maintained by CD4+ CD25+ T regulatory cells (Treg) in animal models of inflammatory bowel diseases. Here we investigated whether Infliximab, a chimeric monoclonal antibody directed against tumour necrosis factor (TNF)-, shown to be highly effective in the treatment of CD, has any effect on mucosal CD4+ CD25+ (FOXP3+) Tregs. Colonic mucosal biopsies from children with active Crohn's disease treated in vivo with Infliximab and controls were analysed to determine FOXP3 expression by immunofluorescence and reverse transcription,polymerase chain reaction. We observed that FOXP3+ T cells were significantly reduced in mucosa of CD patients with active disease compared with controls and restored to normal following Infliximab treatment. The frequency of FOXP3+ cells and mRNA expression was significantly increased in CD mucosa from patients treated in vivo with Infliximab compared with CD patients treated with conventional therapies. In conclusion, we show that Infliximab treatment does not solely neutralize soluble TNF-,, but also affects activation and possibly expansion of mucosal regulatory T cells. We suggest that anti TNF-, immunotherapy can also restore mucosal homeostasis in Crohn's disease. [source] Acute experimental colitis and human chronic inflammatory diseases share expression of inflammation-related genes with conserved Ets2 binding sitesINFLAMMATORY BOWEL DISEASES, Issue 2 2009Tineke C.T.M. van der Pouw Kraan PhD Abstract Background: Ulcerative colitis (UC) and Crohn's disease (CD) are characterized by chronic inflammation of the gastrointestinal tract, with overlapping clinical characteristics and unknown etiology. We reasoned that in intestinal inflammation the initial activation of the innate immune response fails to resolve, finally resulting in uncontrolled chronic inflammatory bowel disease. Methods: To identify the early inflammatory events in colitis that remain active in human chronic colitis, we analyzed the changes of the colonic transcriptome during acute experimental colitis and compared the outcome with previously published profiles of affected tissues from patients with UC and CD, and as a control for intestinal inflammation in general, tissues from celiac disease patients. Rheumatoid arthritis synovial tissues were included as a nonintestinal inflammatory disease. The expression profiles of each disease were analyzed separately, in which diseased tissues were compared to unaffected tissues from the same anatomical location. Results: Gene ontology analysis of significantly regulated genes revealed a marked activation of immunity and defense processes in all diseases, except celiac disease, where immune activation is less prominent. The control region of upregulated genes contained an increase in Ets2 binding sites in experimental colitis, UC, and rheumatoid arthritis, and were associated with upregulated immune activity. In contrast, upregulated genes in celiac disease harbored the transcription factor binding site GLI, which binds to the Gli family of transcription factors involved in hedgehog signaling, affecting development and morphogenesis. Conclusion: Ets2 may be an important transcription factor driving inflammation in acute as well as chronic inflammatory disease. (Inflamm Bowel Dis 2008) [source] Steroid responsiveness in a case of Riedel's thyroiditis and retroperitoneal fibrosisINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 3 2004P.K. Moulik Summary Riedel's thyroiditis is a rare chronic inflammatory disease of the thyroid characterised by an invasive fibrotic process. We present a lady with newly diagnosed hypothyroidism, rapidly enlarging hard, fixed goitre, strongly positive thyroid antibodies and raised erythrocyte sedimentation rate (ESR). A tru-cut biopsy confirmed Riedel's struma. Regression of the goitre and reduction of antibody titres occurred after starting prednisolone, which was stopped after 10 months. Six months later, she presented with renal failure due to retroperitoneal fibrosis that was successfully treated by reinstitution of steroids and ureteric stenting. Very high titres of thyroid antibodies and hypothyroidism predating development of goitre suggest coexistence of Hashimoto's thyroiditis and Riedel's thyroiditis. Tru-cut biopsy obviated the need for open thyroidectomy. A predominantly inflammatory as opposed to fibrotic thyroid histology may predict good response to steroids. Relapse following steroid withdrawal may not only be in the thyroid but also at other sites. [source] Managing comorbidity in patients with rheumatoid arthritisINTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 3 2008Vicky LU Abstract Rheumatoid arthritis (RA) is a chronic inflammatory disease that decreases physical function and imposes substantial medical costs. Comorbid conditions are common in patients with RA and they adversely affect quality of life and RA-related outcomes such as work disability and mortality. Rheumatologists have the important responsibility to consider comorbidities and their risks when treating patients and to adapt therapies to the specific situation of individual patients. This paper discusses the common comorbidities in patients with RA and management approaches. [source] Renal malakoplakia as a pseudotumoral lesion in a renal transplant patient: A case reportINTERNATIONAL JOURNAL OF UROLOGY, Issue 7 2007Isidro Machado Puerto Abstract: Malakoplakia is a rare chronic inflammatory disease associated with gram-negative bacterial infections frequently caused by Escherichia coli. Malakoplakia usually affects the lower urinary tract (bladder) but there are cases described in the kidney as well as in the respiratory and digestive organs. We report on a case with renal parenchymal malakoplakia in a renal transplant patient and describe the pathological lesions of malakoplakia: histiocytic proliferation with scarce inflammatory infiltrate, histiocytes with acidophilic cytoplasm and the presence of characteristic Michaelis-Gutmann bodies. The authors in this study review the updated reports related to the entity in this uncommon localization, the association with an immunocompromised patient, the macroscopic presentation as a pseudotumoral lesion and the possible relationship with the xanthogranulomatous pyelonephritis as a form of a histopathological spectrum in patients affected with gram negative urinary tract infection. [source] Localized lymphedema (elephantiasis): a case series and review of the literatureJOURNAL OF CUTANEOUS PATHOLOGY, Issue 1 2009Song Lu Background:, Lymphedema typically affects a whole limb. Rarely, lymphedema can present as a circumscribed plaque or an isolated skin tumor. Objective:, To describe the clinical and pathologic characteristics and etiologic factors of localized lymphedema. Methods:, Case,control study of skin biopsy and excision specimens histologically diagnosed with lymphedema and presenting as a localized skin tumor identified during a 4-year period. Results:, We identified 24 cases of localized lymphedema presenting as solitary large polyps (11), solid or papillomatous plaques (7), pendulous swellings (4), or tumors mimicking sarcoma (2). Patients were 18 females and 6 males with a mean age of 41 years (range 16,74). Anogenital involvement was most frequent (75%) , mostly vulva (58%), followed by eyelid (13%), thigh (8%) and breast (4%). Causative factors included injury due to trauma, surgery or childbirth (54%), chronic inflammatory disease (rosacea, Crohn's disease) (8%), and bacterial cellulitis (12%). Eighty-five percent of these patients were either overweight (50%) or obese (35%). Compared with a series of 80 patients with diffuse lymphedema, localized lymphedema patients were significantly younger (41 vs. 62 years old, p = 0.0001), had no history of cancer treatment (0% vs. 18%, p = 0.03), and had an injury to the affected site (54% vs. 6%, p = 0.0001). Histologically, all cases exhibited dermal edema, fibroplasia, dilated lymphatic vessels, uniformly distributed stromal cells and varying degrees of papillated epidermal hyperplasia, inflammatory infiltrates and hyperkeratosis. Tumor size significantly and positively correlated with history of cellulitis, obesity, dense inflammatory infiltrates containing abundant plasma cells, and lymphoid follicles (p < 0.05). A history of cellulitis, morbid obesity, lymphoid follicles and follicular cysts predicted recurrent or progressive swelling despite excision (p < 0.05). Conclusions:, Localized lymphedema should be considered in the etiology of skin tumors when assessing a polyp, plaque, swelling or mass showing dermal edema, fibrosis and dilated lymphatics on biopsy. A combination of lymph stasis promoting factors (trauma, obesity, infection and/or inflammatory disorders) produces localized elephantiasis. [source] An immune-complex glomerulonephritis of Chinook salmon, Oncorhynchus tshawytscha (Walbaum)JOURNAL OF FISH DISEASES, Issue 12 2008J S Lumsden Abstract Chinook salmon from New Zealand were shown to have a generalized membranous glomerulonephritis that was most severe in large fish. Marked thickening of the glomerular basement membrane was the most consistent lesion, with the presence of an electron-dense deposit beneath the capillary endothelium. Severely affected glomeruli also had expansion of the mesangium and loss of capillaries, synechiae of the visceral and parietal epithelium and mild fibrosis of Bowman's capsule. Chinook salmon from British Columbia, Canada with bacterial kidney disease caused by Renibacterium salmoninarum had similar histological lesions. They also had thickened glomerular basement membranes that were recognized by rabbit antiserum to rainbow trout immunoglobulin. This was true only when frozen sections of kidney were used and not formalin-fixed tissue. An attempt to experimentally produce a glomerulopathy in rainbow trout by repeated immunization with killed R. salmoninarum was not successful. Case records from the Fish Pathology Laboratory at the University of Guelph over a 10-year period revealed that a range of species were diagnosed with glomerulopathies similar to those seen in Chinook salmon. The majority of these cases were determined to have chronic inflammatory disease. This report has identified the presence of immunoglobulin within thickened basement membranes of Chinook salmon with glomerulonephritis and supports the existence of type III hypersensitivity in fish. [source] Oxidative stress and metabolism in animal model of colitis induced by dextran sulfate sodiumJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 11 2007Carlos R Damiani Abstract Background and Aim:, Ulcerative colitis is a chronic inflammatory disease of the gastrointestinal tract. Its etiology remains unclear, but it appears to result from a dysregulated immune response, with infiltration of phagocytic leukocytes into the mucosal interstitium. The production and release of reactive oxygen species by immune cells seems to play a crucial role in physiopathology of colitis. The aim of this work was to evaluate the effects of N-acetylcysteine (NAC) and deferoxamine (DFX) in the treatment of colitis induced by dextran sulfate sodium (DSS). Methods:, The effects of NAC and DRX on rats with DSS-induced colitis were determined by measuring intestinal parameters of oxidative stress and mitochondrial function, inflammatory response and bowel histopathological alterations. Results:, DSS increased white blood cells count and NAC and DFX did not prevent this effect. However, DSS increased mitochondrial respiratory chain complex IV in colon of rats and NAC and DFX prevented this alteration. In addition, thiobarbituric acid reactive substances were increased in colon of DSS-treated rats. NAC and DFX, when taken together, prevented this effect. Complex II and succinate dehydrogenase were not affected by DSS, as protein carbonyl content. Conclusions:, It is speculated that NAC and DFX might be useful for treatment of colitis, but further research is necessary to clarify these effects. [source] Effect of heme oxygenase-1 induction by octreotide on TNBS-induced colitisJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 11 2007im Erbil Abstract Background and Aim:, Ulcerative colitis is a chronic inflammatory disease of the colon and rectum. Although the precise etiology of ulcerative colitis remains unknown, it is believed to involve an abnormal host response to endogenous or environmental antigens, genetic factors, and oxidative damage. The aim of the present study was to investigate whether heme oxygenase-1 (HO-1) induction by octreotide could protect against oxidative and inflammatory damage from induced colitis. Methods:, Rats received octreotide 50 µg/kg per day intraperitoneally for 5 days before 2,4,6 trinitrobenzene sulfonic acid (TNBS) solution administration and for 15 days following TNBS solution administration. Rats were killed on day 21, and colonic malondialdehyde (MDA) levels, glutathione (GSH) levels and HO-1 expression were measured. Nuclear factor (NF)-,B and HO-1 expression was evaluated by immunohistochemical examination of the colonic tissue. Results:, Rats with TNBS-induced colitis had significantly increased colonic MDA levels and HO-1 expression in comparison to the control group. Octreotide treatment was associated with increased HO-1 expression and GSH levels, but decreased MDA levels. Histopathological examination revealed that the intestinal mucosal structure was preserved in the octreotide-treated group. In addition, treatment with octreotide significantly increased HO-1 expression and decreased NF-,B expression by immunohistochemistry when compared to the TNBS-induced colitis group. Conclusion:, Octreotide appears to have protective effects against colonic damage in TNBS-induced colitis. This protective effect is, in part, mediated by modification of the inflammatory response and the induction of HO-1 expression. [source] Dysfunction of CD4+CD25high T regulatory cells in patients with recurrent aphthous stomatitisJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 8 2008Natalia Lewkowicz Background:, Recurrent aphthous stomatitis (RAS) is a chronic inflammatory disease of unknown etiology characterized by recurring formation of painful oral ulcers. RAS may result from oral epithelium damage caused by T-cell-mediated immune response. CD4+CD25+ T regulatory (Treg) cells suppress proliferation and effector functions of other immune cells, and therefore are crucial in regulating the immune response. Methods:, We tested the function of peripheral CD4+CD25high Treg cells in active RAS through their ability to inhibit proliferation and cytokine production of conventional CD4+ T cells. We also attempted to detect the presence of FOXP3 and indoleamine 2,3-dioxygenase (IDO) mRNA in the lesional and non-lesional oral mucosa of RAS patients and healthy individuals using real-time PCR assay. Results:, Treg cells derived from RAS patients were less efficient in the suppression of cytokine production of CD4+ T effector cells than Treg cells from healthy individuals. Moreover, in RAS, Treg cells were nearly twice less potent in the inhibition of CD4+CD25, T cell proliferation than in healthy donors. Furthermore, we have demonstrated the decreased proportion of CD4+CD25+FOXP3+ Treg cells in peripheral blood of RAS patients compared with controls. We failed to detect FOXP3 mRNA, while IDO mRNA expression was decreased in non-lesional mucosa biopsies from RAS patients compared with ulcer biopsies or normal mucosa from healthy donors. Conclusions:, These findings suggest that CD4+CD25high Treg cells are both functionally and quantitatively compromised in RAS and that decreased constitutive expression of IDO in oral mucosa in RAS may lead to the loss of local immune tolerance. [source] Absence of leukocyte microchimerism in oral lichen planus (OLP): an in situ hybridisation studyJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 7 2001T. Lombardi Abstract: Oral lichen planus (OLP) is a relatively common chronic inflammatory disease. The majority of patients are between 30 and 50 years of age with a higher incidence in females. The aetiology is unknown and various hypotheses on the pathogenic mechanisms, including autoimmunity, have been proposed over the years. In the present study, we investigated whether leukocyte microchimerism, a biological situation implicated in the aetiology of some autoimmune diseases, might play a role in the pathogenesis of OLP. We used in situ hybridisation to identify Y chromosome DNA in a series of formalin-fixed paraffin-embedded oral mucosa biopsies of women with established clinical and histological disease who had given birth to a male child. The positive control, two mucosal specimens from a man with OLP, showed over 90% of keratinocytes and cells within the inflammatory infiltrate, a positive nuclear signal. The negative control, biopsies from three women having carried only female foetuses and one nulliparous woman, all with OLP, did not show any nuclear signal. In the fifteen selected cases of OLP biopsies from women who had only male offspring, nucleated cells containing the Y chromosome were not detected within the chronic inflammatory infiltrate. These results suggest that unlike some other immunologically mediated diseases, leukocyte microchimerism does not seems to be involved in the pathogenesis of OLP. [source] Extracellular neutrophil traps in periodontitisJOURNAL OF PERIODONTAL RESEARCH, Issue 5 2009L. Vitkov Background and Objective:, Chronic periodontitis, the chronic inflammatory disease of the periodontium, is caused by bacteria and is characterized by an influx of neutrophils into the gingival crevice. Recently, a ,new' extracellular neutrophil defense mechanism , neutrophil extracellular traps , has been described. However, their role in periodontitis has not yet been investigated. Material and Methods:, Clinical examinations, transmission and scanning electron microscopy, as well as cytology and confocal laser-scanning microscopy, were employed to analyze gingiva biopsies and crevicular exudate from patients with chronic periodontitis. Results:, An abundance of neutrophil extracellular traps and some phagocytic neutrophils was found on the gingival pocket surface and in the purulent crevicular exudate. Finding neutrophil extracellular traps in the spontaneously effused purulent crevicular exudate clearly indicated that they are flushed from the pocket by the crevicular exudate. In cases of dispersal of subgingival plaque bacteria, their trapping by neutrophil extracellular traps in purulent crevicular exudate and on the gingival surface was demonstrated. Conclusion:, Trapping the crevicular bacteria prevents their adhesion to and invasion of the gingiva. The combination of neutrophil extracellular traps and crevicular exudate outflow appears to be a ,novel' defense mechanism for the clearance of crevicular bacteria in chronic periodontitis. [source] Effects of omalizumab on markers of inflammation in patients with allergic asthmaALLERGY, Issue 12 2009S. Holgate Asthma is a chronic inflammatory disease of the airways in which immunoglobulin E (IgE) plays a key role by activating a variety of inflammatory cells through interactions with Fc,RI and Fc,RII receptors. The role of IgE in allergic inflammation provided the rationale for developing omalizumab, a humanized monoclonal anti-IgE antibody, for patients with moderate-to-severe or severe allergic asthma. The reductions in circulating levels of IgE resulting from omalizumab treatment leads to reductions in Fc,RI expression on mast cells, basophils and dendritic cells. This combined effect results in attenuation of several markers of inflammation, including peripheral and bronchial tissue eosinophilia and levels of granulocyte macrophage colony stimulating factor, interleukin (IL)-2, IL-4, IL-5 and IL-13. By blocking IgE binding to its receptors and diminishing dendritic cell Fc,RI receptor expression, omalizumab may also reduce allergen presentation to T cells and the production of Th2 cytokines. The anti-inflammatory effects of omalizumab may, therefore, explain the reductions in asthma exacerbations and symptoms seen in clinical trials in patients with moderate-to-severe or severe, persistent, inadequately controlled allergic asthma. [source] The role of small airways in monitoring the response to asthma treatment: what is beyond FEV1?ALLERGY, Issue 11 2009N. Scichilone The definition of asthma has evolved from that of an episodic disease characterized by reversible airways constriction to a chronic inflammatory disease of the airways, with at least partially reversible airway constriction. Increasing evidence supports the notion that small and large airways play a central role in asthma pathophysiology with regard to inflammation, remodeling and symptoms. The contribution of the distal airways to the asthma phenotype carries implications for the delivery of inhaled medications to the appropriate areas of the lung and for the monitoring of the response to asthma treatment. Asthma control is evaluated on the basis of symptoms, lung function and exacerbations. However, evidence suggests that dissociation between lung function and respiratory symptoms, quality of life and airway inflammation exists. In this study, common spirometric parameters offer limited information with regard to the peripheral airways, and it is therefore necessary to move beyond FEV1. Several functional parameters and inflammatory markers, which are discussed in the present study, can be employed to evaluate distal lung function. In this study, extrafine formulations deliver inhaled drugs throughout the bronchial tree (both large and small airways) and are effective on parameters that directly or indirectly measure air trapping/airway closure. [source] Glycogen synthase kinase 3 (GSK-3) inhibitors as new promising drugs for diabetes, neurodegeneration, cancer, and inflammationMEDICINAL RESEARCH REVIEWS, Issue 4 2002Ana Martinez Abstract Glycogen synthase kinase 3 (GSK-3) was initially described as a key enzyme involved in glycogen metabolism, but is now known to regulate a diverse array of cell functions. Two forms of the enzyme, GSK-3, and GSK-3,, have been previously identified. Small molecules inhibitors of GSK-3 may, therefore, have several therapeutic uses, including the treatment of neurodegenerative diseases, diabetes type II, bipolar disorders, stroke, cancer, and chronic inflammatory disease. As there is lot of recent literature dealing with the involvement of GSK-3 in the molecular pathways of different diseases, this review is mainly focused on the new GSK-3 inhibitors discovered or specifically developed for this enzyme, their chemical structure, synthesis, and structure,activity relationships, with the aim to provide some clues for the future optimization of these promising drugs. © 2002 Wiley Periodicals, Inc. Med Res Rev, 22, No. 4, 373,384, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/med.10011 [source] Relation between inflammation and symptoms in asthmaALLERGY, Issue 3 2009I. Tillie-Leblond Asthma symptoms are the main reason for healthcare utilization and are a fundamental parameter for the evaluation of asthma control. Currently, asthma is defined as a chronic inflammatory disease. A French expert group studied the association between inflammation and asthma symptoms by carrying out a critical review of the international literature. Uncontrolled asthmatics have an increased number of polynuclear eosinophils in the induced sputum and an increased production of exhaled NO. Control by anti-inflammatory treatment is accompanied by a reduction in bronchial eosinophilia and exhaled NO. Asthma symptoms are the result of complex mechanisms and many factors modify their perception. Experimental data suggest that there is a relationship between the perception of symptoms and eosinophilic inflammation and that inhaled corticoid therapy improves this perception. Although they are still not applicable in routine practice, follow-up strategies based on the evaluation of inflammation are thought to be more effective in reducing exacerbations than those usually recommended based on symptoms and sequential analysis of respiratory function. Inhaled corticosteroid therapy is the reference disease-modifying therapy for persistent asthma. Recent studies demonstrated that adjustment of anti-inflammatory treatment based on symptoms is an effective strategy to prevent exacerbations and reduce the total number of doses of inhaled corticosteroids. [source] Chronic rhinosinusitis and nasal polyps: the role of generic and specific questionnaires on assessing its impact on patient's quality of lifeALLERGY, Issue 10 2008I. Alobid Chronic rhinosinusitis (CRS) including nasal polyps is a chronic inflammatory disease of the nasal and paranasal sinus mucosa that, despite differing hypotheses of its cause, remains poorly understood. Primary symptoms are nasal blockage, loss of smell, rhinorrhea, and facial pain or pressure. Chronic rhinosinusitis causes significant physical symptoms, has a negative impact on quality of life (QoL), and can substantially impair daily functioning. A global evaluation of patients must include, together with nasal symptoms, nasal endoscopy, and CT scan, the measurement of QoL. To assess QoL in CRS, specific and generic questionnaires may be used. Chronic rhinosinusitis has a considerable impact on a patient's QoL but comorbidities, such as asthma and atopy, have an accumulative negative effect. Both medical and surgical treatments lead to a similar improvement on the QoL of CRS and nasal polyp patients. [source] Basement membrane thickening and clinical features of children with asthmaALLERGY, Issue 6 2007E. S. Kim Background:, Asthma is a chronic inflammatory disease, characterized by airway inflammation, bronchial hyper-responsiveness, and airway obstruction. Although asthma induces partially reversible airway obstruction, obstruction can sometimes become irreversible. This may be a consequence of airway remodeling, which includes a number of structural changes, such as epithelial detachment, basement membrane (BM) thickening, smooth muscle hypertrophy, and new vessel formation. This study evaluated children with asthma for the presence of BM thickening. Methods:, Eighteen children with asthma and 24 control subjects underwent flexible bronchoscopy with endobronchial biopsy. Light microscopy was used to measure BM thickness in paraffin-embedded biopsy sections. The association between BM thickening and age, sex, duration of asthma, asthma severity, FEV1, FEV1/FVC, FEF25,75%, methacholine PC20, eosinophil count, and presence of atopy was examined. Results:, Basement membrane thickness was greater in subjects with asthma (8.3 ± 1.4 ,M) than in control subjects (6.8 ± 1.3 ,M, P = 0.0008). Multiple regression analysis revealed that sex, FEV1/FVC, total IgE, and atopy (IgE for Dermatophagoides pteronyssinus >0.34 kUA/l) were significant predictive factors for BM thickness. There was no significant association between BM thickness and age, duration of asthma, FEV1, FEF25,75%, methacholine PC20, eosinophil count, or asthma severity. Conclusions:, Basement membrane thickening has been known to be present in children with asthma. In addition, we report an association between BM thickness and sex, FEV1/FVC, total IgE, and the presence of IgE specific to D. pteronyssinus. [source] Effects of oral alpha-tocopherol on lung response in rat model of allergic asthmaRESPIROLOGY, Issue 4 2006Jana SUCHANKOVA Objective and background: Asthma is a chronic inflammatory disease in which an oxidant/antioxidant imbalance plays an important role. d -alpha-tocopherol (biologically the most active form of vitamin E) has redox properties and by scavenging the free radicals can act as an antioxidant. The aim of this study was to examine the effects of orally administered alpha-tocopherol in a rat model of allergic asthma. Methodology: Actively sensitized rats (OA) were treated with alpha-tocopherol (400 mg/kg/day for 10 days) or vehicle; 1 h after the last dose, they were challenged with antigen aerosol. The antigen-induced airway hyperresponsiveness to direct bronchoconstrictor (serotonin), the inflammatory cell infiltrate and histological changes were determined 1 or 24 h after the antigen challenge. Results: Alpha-tocopherol pretreatment was not significantly effective at reducing the studied parameters when compared with controls, even though there was a tendency to a reduction in bronchial responsiveness and in eosinophil and neutrophil infiltration. Conclusion: Alpha-tocopherol when administered in the chosen study design in an animal model of asthma had no major effect on airway inflammation. The effect of antioxidants deserves further evaluation. [source] Protective Effect of the Immunosuppressant Sirolimus Against Aortic Atherosclerosis In Apo E-Deficient MiceAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2003M. Merle Elloso Atherosclerosis is a chronic inflammatory disease that develops in response to injury to the vessel wall, and is augmented by hypercholesterolemia. To further delineate the role of the immune system and local factors in this process, we assessed the effects of the immunosuppressant sirolimus (Rapamycin, RAPAMUNE®, Wyeth, Collegeville, PA) on atherosclerosis in the apoE-deficient (apoE KO) mouse, a well-accepted model of cardiovascular disease. ApoE KO mice were fed a high fat diet and sirolimus was administered. After 12 weeks, atherosclerotic lesions and plasma lipoproteins were measured. The expression of cytokines associated with atherosclerosis was also examined. All groups demonstrated plasma total cholesterol (TC) >1100 mg/dL. Sirolimus treatment was associated with a 30% increase in LDL-cholesterol (LDLc) and a dose-dependent elevation in HDL-cholesterol (HDLc). Despite increased LDLc, aortic atherosclerosis was markedly reduced in all sirolimus-treated groups. Sirolimus treatment resulted in decreased expression of IL-12p40, IFN-, and IL-10 mRNA. In contrast, TGF-,1 was elevated. Sirolimus significantly reduced atherosclerosis in apo E-KO mice; this effect is independent of, and obviates, elevated plasma TC and LDLc. Sirolimus might therefore be of benefit on atherosclerosis in patients undergoing therapy, independent of any impact on circulating lipids. [source] Killer immunoglobulin-like receptor ligand HLA-Bw4 protects against multiple sclerosis,ANNALS OF NEUROLOGY, Issue 6 2009Åslaug R. Lorentzen MD Objective Multiple sclerosis (MS) is a chronic inflammatory disease affecting the central nervous system. A human leukocyte antigen (HLA) class II association is well established (DRB1*1501-DQB1*0602), but more recently HLA class II,independent associations with HLA class I variants have also been reported. The HLA class I (HLA-A, -B, -C) molecules serve as ligands for both T-cell receptors and killer immunoglobulin-like receptors (KIRs). We investigated the HLA class I alleles defined by their KIR binding motifs and the KIR genes to evaluate whether these genes could influence MS susceptibility or severity, alone or in combination. Methods We typed Norwegian MS patients (n = 631) and controls (n = 555) for HLA-A, -B, -C and -DRB1 alleles as well as the presence or absence of genes encoding inhibitory (KIR2DL1, KIR2DL2, KIR2DL3, KIR2DL5, KIR3DL1, KIR3DL2, KIR3DL3) and activating (KIR2DS1, KIR2DS2, KIR2DS3, KIR2DL4, KIR2DS4, KIR2DS5, KIR3DS1) KIRs. Results The frequency of the HLA-Bw4 specificity, which is the ligand for the inhibitory KIR3DL1, was significantly reduced in MS patients as compared with controls (41.4% vs 55.1%, puncorrected (uc) = 4.6 × 10,6). Also after stratifying for known HLA class II associations, the HLA-Bw4 association was seen (puc = 0.002). No significant differences in gene carrier frequencies of inhibitory and activating KIRs were observed. However, our data indicate that MS patients who carry the activating KIR2DS2 and the inhibitory KIR2DL2 genes have more severe disease than patients not carrying these genes. Interpretation Carriage of the ligand of the inhibitory KIR3DL1 receptor, HLA-Bw4, was found to protect against MS in an HLA-DRB1 independent manner. Ann Neurol 2009;65:658,666 [source] Genetic interaction of CTLA-4 with HLA-DR15 in multiple sclerosis patients,ANNALS OF NEUROLOGY, Issue 1 2003Mehdi Alizadeh PhD Multiple sclerosis is a chronic inflammatory disease of the central nervous system with a genetic component. Until now, the more consistent association with the disease is found with the major histocompatibility complex, especially HLA-DRB1*1501-DQB1*0602 haplotype. In this report, we demonstrate the interaction of Cytotoxic T Lymphocyte-associated antigen 4 (CTLA-4 [CD152]) gene with DRB1*15 haplotype in multiple sclerosis genetic susceptibility. Our data were obtained from two European independent family-based studies including 610 multiple sclerosis family trios. Ann Neurol 2003;54:119,122 [source] Independent association of rheumatoid arthritis with increased left ventricular mass but not with reduced ejection fractionARTHRITIS & RHEUMATISM, Issue 1 2009Rebecca L. Rudominer Objective Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with premature atherosclerosis, vascular stiffening, and heart failure. This study was undertaken to investigate whether RA is associated with underlying structural and functional abnormalities of the left ventricle (LV). Methods Eighty-nine RA patients without clinical cardiovascular disease and 89 healthy matched controls underwent echocardiography, carotid ultrasonography, and radial tonometry to measure arterial stiffness. RA patients and controls were similar in body size, hypertension and diabetes status, and cholesterol level. Results LV diastolic diameter (4.92 cm versus 4.64 cm; P < 0.001), mass (136.9 gm versus 121.7 gm; P = 0.004 or 36.5 versus 32.9 gm/m2.7; P = 0.01), ejection fraction (71% versus 67%; P < 0.001), and prevalence of LV hypertrophy (18% versus 6.7%; P = 0.023) were all higher among RA patients versus controls. In multivariate analysis, presence of RA was an independent correlate of LV mass (P = 0.004). Furthermore, RA was independently associated with presence of LV hypertrophy (odds ratio 4.14 [95% confidence interval 1.24, 13.80], P = 0.021). Among RA patients, age at diagnosis and disease duration were independently related to LV mass. RA patients with LV hypertrophy were older and had higher systolic pressure, damage index scores, C-reactive protein levels, homocysteine levels, and arterial stiffness compared with those without LV hypertrophy. Conclusion The present results demonstrate that RA is associated with increased LV mass. Disease duration is independently related to increased LV mass, suggesting a pathophysiologic link between chronic inflammation and LV hypertrophy. In contrast, LV systolic function is preserved in RA patients, indicating that systolic dysfunction is not an intrinsic feature of RA. [source] Predicting the course of juvenile dermatomyositis: Significance of early clinical and laboratory featuresARTHRITIS & RHEUMATISM, Issue 11 2008Elizabeth Stringer Objective Juvenile dermatomyositis (DM) is a rare chronic inflammatory disease of childhood. The clinical course of juvenile DM appears to be variable, and little is known about predictors of the disease course. The aims of this study were to describe the clinical course of juvenile DM and to determine whether early clinical and laboratory features can be used to predict the time to remission and/or the disease course. Methods Clinical and laboratory data from a cohort of 84 patients with juvenile DM were prospectively entered into a database (1990,2005). Remission was defined as a clinical state of no active skin rash, weakness, or elevated muscle enzyme levels for 6 months off medication. The disease course was defined as monophasic, polyphasic, or chronic. Data were reviewed at the time of diagnosis and at 3 months and 6 months after the diagnosis to determine predictors of the time to remission and/or the disease course. Results The median time to remission was 4.67 years. Sixty percent of patients had a chronic course, 37% a monophasic course, and 3% a polyphasic course. The presence of rash (most strongly indicated by Gottron's papules) at 3 months was the earliest predictor of a longer time to remission (relative risk [RR] 0.55 [95% confidence interval (95% CI) 0.37,0.81], P = 0.002). At 6 months, the presence of nailfold abnormalities and rash also predicted a longer time to remission (RR 0.35 [95% CI 0.14,0.74], P = 0.003). We were unable to determine a prediction model of disease course. Conclusion The majority of patients in our cohort had a chronic disease course. The persistence of Gottron's papules and nailfold abnormalities early in the disease course was associated with a longer time to remission. [source] | ||||||||||||||||||||||||||||||||||||||||