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Sample records for understood chronic inflammation

  1. Glucocorticoids and chronic inflammation.

    Science.gov (United States)

    Straub, Rainer H; Cutolo, Maurizio

    2016-12-01

    Glucocorticoids are steroid hormones that once bound to their receptor interact with the DNA binding domain. Almost 1000-2000 genes are sensitive to their effects, including immune/inflammatory response genes. However, their role in pathophysiology and therapy is still debated. We performed a literature survey using the key words glucocorticoids, inflammation, autoimmune disease, rheumatology and adrenal glands in order to define important targets for this review on glucocorticoids. Considering endogenous/exogenous glucocorticoids in chronic inflammatory diseases brought up five major points for discussion: inadequately low production of endogenous cortisol relative to systemic inflammation (the disproportion principle); changes of the systemic and local cortisol-to-cortisone shuttle (reactivation and degradation of cortisol); inflammation-induced glucocorticoid resistance; highlights of present glucocorticoid therapy; and the role of circadian rhythms in action of cortisol. Much of this information becomes understandable in the context of neurohormonal energy regulation as recently summarized. The optimization of long-term low-dose glucocorticoid therapy in chronic inflammatory diseases arises from the understanding of the above mentioned aspects. Since glucocorticoid resistance is a consequence of inflammation, adequate anti-inflammatory therapy is mandatory. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  2. Anemia of Inflammation and Chronic Disease

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    ... is anemia of inflammation and chronic disease (AI/ACD)? Anemia of inflammation and chronic disease is a ... after iron-deficiency anemia. 1 Who gets AI/ACD? While AI/ACD can affect people at any ...

  3. Insulin resistance and chronic inflammation

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    Natalia Matulewicz

    2016-12-01

    Full Text Available Insulin resistance is a condition of reduced biological response to insulin. Growing evidence indicates the role of the chronic low-grade inflammatory response in the pathogenesis of insulin resistance. Adipose tissue in obesity is characterized by increased lipolysis with the excessive release of free fatty acids, and is also a source of proinflammatory cytokines. Both these factors may inhibit insulin action. Proinflammatory cytokines exert their effect by stimulating major inflammatory NFκB and JNK pathways within the cells. Inflammatory processes in other insulin responsive tissues may also play a role in inducing insulin resistance. This paper is an overview of the chronic low-grade inflammation in adipose tissue, skeletal muscle, liver and endothelial cells during the development of insulin resistance.

  4. Modeling of chronic ovary inflammation

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    N. А. Volkova

    2014-04-01

    Full Text Available In our country preservation of the population reproductive health is a high-priority direction of modern medicine. In many cases, the cause of reproductive disorders in women is a chronic infectious inflammation of the small pelvis, the frequency of which in recent years had no tendency to decrease. The choice of inactivated vaccine of Staphylococcus aureus as a phlogogen was due to the fact that the etiological role of the aerobic infection remains the leading one in gynecological pathology. The aim of research was studying of the ability to use the inactivated vaccine of Staphylococcus aureus strain 209 for modeling of chronic inflammation of the ovaries in laboratory mice. Materials and methods. 25 mature outbred white female mice weighing 18-20 g were used as experimental animals, which formed next groups: 1 control (n=5 – animals without any interventions and 2 experimental (n=20 – animals with one-fold intraperitoneal injection of inactivated Staphylococcus aureus strain 209 vaccine in the dose of 50х106 microbial bodies in 0,3 ml of physiological solution. Efficiency of the modeling pathology was performed by histomorphometric and hematological methods on the 7th, 14th, 21st and 31st days. All the manipulations with animals were carried out in accordance to the requirements of bioethics and the international principles of the European Convention for the protection of vertebrate animals. For statistical study ANOVA and t-Student tests were used with application of Microsoft Excel Program. Results. In the group of control animals the form and histological structure of ovaries were regular for mature mice without signs of inflammatory changes. The leukocyte infiltration, hemodynamic disorders and minor dystrophic changes of granulosa cells were determined on the 7th day in the ovaries of experimental animals. The increasing of observation period up to 14 days on the background of hemodynamic disorders resulted in the appearance of

  5. Microbiota, Immune Subversion, and Chronic Inflammation.

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    Kramer, Carolyn D; Genco, Caroline Attardo

    2017-01-01

    Several host-adapted pathogens and commensals have evolved mechanisms to evade the host innate immune system inducing a state of low-grade inflammation. Epidemiological studies have also documented the association of a subset of these microorganisms with chronic inflammatory disorders. In this review, we summarize recent studies demonstrating the role of the microbiota in chronic inflammatory diseases and discuss how specific microorganisms subvert or inhibit protective signaling normally induced by toll-like receptors (TLRs). We highlight our work on the oral pathogen Porphyromonas gingivalis and discuss the role of microbial modulation of lipid A structures in evasion of TLR4 signaling and resulting systemic immunopathology associated with atherosclerosis. P. gingivalis intrinsically expresses underacylated lipid A moieties and can modify the phosphorylation of lipid A, leading to altered TLR4 signaling. Using P. gingivalis mutant strains expressing distinct lipid A moieties, we demonstrated that expression of antagonist lipid A was associated with P. gingivalis -mediated systemic inflammation and immunopathology, whereas strains expressing agonist lipid A exhibited modest systemic inflammation. Likewise, mice deficient in TLR4 were more susceptible to vascular inflammation after oral infection with P. gingivalis wild-type strain compared to mice possessing functional TLR4. Collectively, our studies support a role for P. gingivalis -mediated dysregulation of innate and adaptive responses resulting in immunopathology and systemic inflammation. We propose that anti-TLR4 interventions must be designed with caution, given the balance between the protective and destructive roles of TLR signaling in response to microbiota and associated immunopathologies.

  6. Chronic peripheral inflammation, hippocampal neurogenesis, and behavior.

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    Chesnokova, Vera; Pechnick, Robert N; Wawrowsky, Kolja

    2016-11-01

    Adult hippocampal neurogenesis is involved in memory and learning, and disrupted neurogenesis is implicated in cognitive impairment and mood disorders, including anxiety and depression. Some long-term peripheral illnesses and metabolic disorders, as well as normal aging, create a state of chronic peripheral inflammation. These conditions are associated with behavioral disturbances linked to disrupted adult hippocampal neurogenesis, such as cognitive impairment, deficits in learning and memory, and depression and anxiety. Pro-inflammatory cytokines released in the periphery are involved in peripheral immune system-to-brain communication by activating resident microglia in the brain. Activated microglia reduce neurogenesis by suppressing neuronal stem cell proliferation, increasing apoptosis of neuronal progenitor cells, and decreasing survival of newly developing neurons and their integration into existing neuronal circuits. In this review, we summarize evolving evidence that the state of chronic peripheral inflammation reduces adult hippocampal neurogenesis, which, in turn, produces the behavioral disturbances observed in chronic inflammatory disorders. As there are no data available on neurogenesis in humans with chronic peripheral inflammatory disease, we focus on animal models and, in parallel, consider the evidence of cognitive disturbance and mood disorders in human patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Gut inflammation in chronic fatigue syndrome

    OpenAIRE

    Lakhan, Shaheen E; Kirchgessner, Annette

    2010-01-01

    Abstract Chronic fatigue syndrome (CFS) is a debilitating disease characterized by unexplained disabling fatigue and a combination of accompanying symptoms the pathology of which is incompletely understood. Many CFS patients complain of gut dysfunction. In fact, patients with CFS are more likely to report a previous diagnosis of irritable bowel syndrome (IBS), a common functional disorder of the gut, and experience IBS-related symptoms. Recently, evidence for interactions between the intestin...

  8. PROGRESSION VARIANTS OF CHRONIC SYSTEMIC INFLAMMATION

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    E. Y. Gusev

    2009-01-01

    Full Text Available Abstract. Fourteen groups of patients have been investigated and divided into 2 classes. The first class included the following cohorts of patients: relatively healthy persons, age 18 to 55 yrs (n = 50; elderly persons 60 yrs old, as well as senior persons (n = 22; persons with chronic adnexitis, women in their 1st trimester of pregnancy (n = 16; climacteric syndrome (n = 16; autoimmune thyroiditis (n = 29. The second class of patients included following cohorts: elderly persons with chronic cardiac insufficiency (CCI II-III stage (n=49; valvular cardiac disease (rheumatism, n = 15; psoriatic arthritis (n = 12; reactive arthritis (n = 17; antiphospholipid syndrome, a sub-group in the 1st trimester of pregnancy (n = 5; systemic lupus erythematosus (n=49; decompensated atherosclerosis of femoral artery (n = 38; end-stage renal disease (n = 42. Plasma cytokines (TNFαα, IL-6, IL-8, IL-10, acute-phase C-reactive protein (CRP, cortisol, troponin I, myoglobin, D-dimers, interleukin-2 soluble receptor (IL-2sR, and eosinophil cationic protein (ECP were determined in all the patients, by means of immune chemiluminescent technique (Immulite; Siemens Medical Solutions Diagnostics, USA. The integral indices of systemic inflammatory reaction (SIR have been calculated, i.e., a Reactivity Coefficient (RC and a Reactivity Level (RL. In the patients belonging to Class 1 cohorts, an absence of chronic systemic inflammation features was revealed, despite of some signs of systemic inflammatory response. Meanwhile, a majority of Class 2 patients have shown the signs of chronic systemic inflammation stage I to III.

  9. Chronic systemic inflammation originating from epithelial tissues.

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    Uluçkan, Özge; Wagner, Erwin F

    2017-02-01

    Chronic systemic inflammation (CSI) has recently been identified as a major contributor to common diseases ranging from cancer to metabolic disorders and neurologic alterations. In the last decade, we and others have generated genetically engineered mouse models for inflammatory diseases, which enable studying the molecular mechanisms of CSI. Recently, organ cross-talk induced by CSI under homeostatic and pathological conditions has begun to be appreciated. In this review, we will revisit whole organism physiology in relation to CSI originating from epithelial tissues, such as the skin and gut. Furthermore, we will discuss the current knowledge regarding the mechanisms, the specific immune cells and molecules responsible for inducing the most common comorbidities, such as cardiovascular, metabolic, and neurological complications, as well as bone loss, in heterogeneous diseases like psoriasis, atopic dermatitis, and inflammatory bowel disease. As it would be impossible to discuss all comorbidities of these diseases as well as all epithelial tissues, we present an overview with a special emphasis on our recent findings linking skin inflammation to bone loss. © 2016 Federation of European Biochemical Societies.

  10. Chronic inflammation induces telomere dysfunction and accelerates ageing in mice

    NARCIS (Netherlands)

    Jurk, Diana; Wilson, Caroline; Passos, Joao F.; Oakley, Fiona; Correia-Melo, Clara; Greaves, Laura; Saretzki, Gabriele; Fox, Chris; Lawless, Conor; Anderson, Rhys; Hewitt, Graeme; Pender, Sylvia L. F.; Fullard, Nicola; Nelson, Glyn; Mann, Jelena; van de Sluis, Bart; Mann, Derek A.; von Zglinicki, Thomas

    Chronic inflammation is associated with normal and pathological ageing. Here we show that chronic, progressive low-grade inflammation induced by knockout of the nfkb1 subunit of the transcription factor NF-kappa B induces premature ageing in mice. We also show that these mice have reduced

  11. SOCS and inflammation in chronic renal failure

    OpenAIRE

    Rastmanesh, M.M.

    2008-01-01

    Atherosclerosis is the major cause of morbidity and mortality in renal patients and a major health concern in western countries per se. Recent studies point to the important role of inflammation as an underlying cause of atherosclerosis. Importantly medicines that suppress inflammation lower the incidence of atherosclerosis as well. This indicates the importance of molecules that are able to control inflammation. Inflammation in renal patients is characterized by increased plasma levels of in...

  12. Curcumin, Inflammation, and Chronic Diseases: How Are They Linked?

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    Yan He

    2015-05-01

    Full Text Available It is extensively verified that continued oxidative stress and oxidative damage may lead to chronic inflammation, which in turn can mediate most chronic diseases including cancer, diabetes, cardiovascular, neurological, inflammatory bowel disease and pulmonary diseases. Curcumin, a yellow coloring agent extracted from turmeric, shows strong anti-oxidative and anti-inflammatory activities when used as a remedy for the prevention and treatment of chronic diseases. How oxidative stress activates inflammatory pathways leading to the progression of chronic diseases is the focus of this review. Thus, research to date suggests that chronic inflammation, oxidative stress, and most chronic diseases are closely linked, and the antioxidant properties of curcumin can play a key role in the prevention and treatment of chronic inflammation diseases.

  13. SOCS and inflammation in chronic renal failure

    NARCIS (Netherlands)

    Rastmanesh, M.M.

    2008-01-01

    Atherosclerosis is the major cause of morbidity and mortality in renal patients and a major health concern in western countries per se. Recent studies point to the important role of inflammation as an underlying cause of atherosclerosis. Importantly medicines that suppress inflammation lower the

  14. Radiopharmaceuticals for imaging chronic lymphocytic inflammation

    NARCIS (Netherlands)

    Malviya, Gaurav; De Vries, Erik F. J.; Dierckx, Rudi A.; Signore, Alberto

    In the last few decades, a number of radiopharmaceuticals for imaging inflammation have been proposed that differ in their specificity and mechanism of uptake in inflamed foci as compared to the traditional inflammation imaging agents. Radiolabelled cytokines represent a reliable tool for the

  15. Gut inflammation in chronic fatigue syndrome

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    Kirchgessner Annette

    2010-10-01

    Full Text Available Abstract Chronic fatigue syndrome (CFS is a debilitating disease characterized by unexplained disabling fatigue and a combination of accompanying symptoms the pathology of which is incompletely understood. Many CFS patients complain of gut dysfunction. In fact, patients with CFS are more likely to report a previous diagnosis of irritable bowel syndrome (IBS, a common functional disorder of the gut, and experience IBS-related symptoms. Recently, evidence for interactions between the intestinal microbiota, mucosal barrier function, and the immune system have been shown to play a role in the disorder's pathogenesis. Studies examining the microecology of the gastrointestinal (GI tract have identified specific microorganisms whose presence appears related to disease; in CFS, a role for altered intestinal microbiota in the pathogenesis of the disease has recently been suggested. Mucosal barrier dysfunction promoting bacterial translocation has also been observed. Finally, an altered mucosal immune system has been associated with the disease. In this article, we discuss the interplay between these factors in CFS and how they could play a significant role in GI dysfunction by modulating the activity of the enteric nervous system, the intrinsic innervation of the gut. If an altered intestinal microbiota, mucosal barrier dysfunction, and aberrant intestinal immunity contribute to the pathogenesis of CFS, therapeutic efforts to modify gut microbiota could be a means to modulate the development and/or progression of this disorder. For example, the administration of probiotics could alter the gut microbiota, improve mucosal barrier function, decrease pro-inflammatory cytokines, and have the potential to positively influence mood in patients where both emotional symptoms and inflammatory immune signals are elevated. Probiotics also have the potential to improve gut motility, which is dysfunctional in many CFS patients.

  16. Immunosuppression associated with chronic inflammation in the tumor microenvironment

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    Wang, Dingzhi; DuBois, Raymond N.

    2015-01-01

    Chronic inflammation contributes to cancer development via multiple mechanisms. One potential mechanism is that chronic inflammation can generate an immunosuppressive microenvironment that allows advantages for tumor formation and progression. The immunosuppressive environment in certain chronic inflammatory diseases and solid cancers is characterized by accumulation of proinflammatory mediators, infiltration of immune suppressor cells and activation of immune checkpoint pathways in effector T cells. In this review, we highlight recent advances in our understanding of how immunosuppression contributes to cancer and how proinflammatory mediators induce the immunosuppressive microenvironment via induction of immunosuppressive cells and activation of immune checkpoint pathways. PMID:26354776

  17. Biofilms and Inflammation in Chronic Wounds

    Science.gov (United States)

    Zhao, Ge; Usui, Marcia L.; Lippman, Soyeon I.; James, Garth A.; Stewart, Philip S.; Fleckman, Philip; Olerud, John E.

    2013-01-01

    Significance The incidence, cost, morbidity, and mortality associated with non-healing of chronic skin wounds are dramatic. With the increasing numbers of people with obesity, chronic medical conditions, and an increasing life expectancy, the healthcare cost of non-healing ulcers has recently been estimated at $25 billion annually in the United States. The role played by bacterial biofilm in chronic wounds has been emphasized in recent years, particularly in the context of the prolongation of the inflammatory phase of repair. Recent Advances Rapid high-throughput genomic approaches have revolutionized the ability to identify and quantify microbial organisms from wounds. Defining bacterial genomes and using genetic approaches to knock out specific bacterial functions, then studying bacterial survival on cutaneous wounds is a promising strategy for understanding which genes are essential for pathogenicity. Critical Issues When an animal sustains a cutaneous wound, understanding mechanisms involved in adaptations by bacteria and adaptations by the host in the struggle for survival is central to development of interventions that favor the host. Future Directions Characterization of microbiomes of clinically well characterized chronic human wounds is now under way. The use of in vivo models of biofilm-infected cutaneous wounds will permit the study of the mechanisms needed for biofilm formation, persistence, and potential synergistic interactions among bacteria. A more complete understanding of bacterial survival mechanisms and how microbes influence host repair mechanisms are likely to provide targets for chronic wound therapy. PMID:24527355

  18. Inflammation and nutrition in children with chronic kidney disease

    OpenAIRE

    Tu, Juan; Cheung, Wai W; Mak, Robert H

    2016-01-01

    Chronic inflammation and nutritional imbalance are important comorbid conditions that correlate with poor clinical outcomes in children with chronic kidney disease (CKD). Nutritional disorders such as cachexia/protein energy wasting, obesity and growth retardation negatively impact the quality of life and disease progression in children with CKD. Inadequate nutrition has been associated with growth disturbances in children with CKD. On the other hand, over-nutrition and obesity are associated...

  19. Pathogenesis of Myeloproliferative Neoplasms: Role and Mechanisms of Chronic Inflammation

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    Bigot-Corbel, Edith; Gardie, Betty

    2015-01-01

    Myeloproliferative neoplasms (MPNs) are a heterogeneous group of clonal diseases characterized by the excessive and chronic production of mature cells from one or several of the myeloid lineages. Recent advances in the biology of MPNs have greatly facilitated their molecular diagnosis since most patients present with mutation(s) in the JAK2, MPL, or CALR genes. Yet the roles played by these mutations in the pathogenesis and main complications of the different subtypes of MPNs are not fully elucidated. Importantly, chronic inflammation has long been associated with MPN disease and some of the symptoms and complications can be linked to inflammation. Moreover, the JAK inhibitor clinical trials showed that the reduction of symptoms linked to inflammation was beneficial to patients even in the absence of significant decrease in the JAK2-V617F mutant load. These observations suggested that part of the inflammation observed in patients with JAK2-mutated MPNs may not be the consequence of JAK2 mutation. The aim of this paper is to review the different aspects of inflammation in MPNs, the molecular mechanisms involved, the role of specific genetic defects, and the evidence that increased production of certain cytokines depends or not on MPN-associated mutations, and to discuss possible nongenetic causes of inflammation. PMID:26538820

  20. Systems Approaches to Modeling Chronic Mucosal Inflammation

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    Gao, Boning; Choudhary, Sanjeev; Wood, Thomas G.; Carmical, Joseph R.; Boldogh, Istvan; Mitra, Sankar; Minna, John D.; Brasier, Allan R.

    2013-01-01

    The respiratory mucosa is a major coordinator of the inflammatory response in chronic airway diseases, including asthma and chronic obstructive pulmonary disease (COPD). Signals produced by the chronic inflammatory process induce epithelial mesenchymal transition (EMT) that dramatically alters the epithelial cell phenotype. The effects of EMT on epigenetic reprogramming and the activation of transcriptional networks are known, its effects on the innate inflammatory response are underexplored. We used a multiplex gene expression profiling platform to investigate the perturbations of the innate pathways induced by TGFβ in a primary airway epithelial cell model of EMT. EMT had dramatic effects on the induction of the innate pathway and the coupling interval of the canonical and noncanonical NF-κB pathways. Simulation experiments demonstrate that rapid, coordinated cap-independent translation of TRAF-1 and NF-κB2 is required to reduce the noncanonical pathway coupling interval. Experiments using amantadine confirmed the prediction that TRAF-1 and NF-κB2/p100 production is mediated by an IRES-dependent mechanism. These data indicate that the epigenetic changes produced by EMT induce dynamic state changes of the innate signaling pathway. Further applications of systems approaches will provide understanding of this complex phenotype through deterministic modeling and multidimensional (genomic and proteomic) profiling. PMID:24228254

  1. Dietary and Endogenous Sphingolipid Metabolism in Chronic Inflammation

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    Gregory H. Norris

    2017-10-01

    Full Text Available Chronic inflammation is a common underlying factor in many major metabolic diseases afflicting Western societies. Sphingolipid metabolism is pivotal in the regulation of inflammatory signaling pathways. The regulation of sphingolipid metabolism is in turn influenced by inflammatory pathways. In this review, we provide an overview of sphingolipid metabolism in mammalian cells, including a description of sphingolipid structure, biosynthesis, turnover, and role in inflammatory signaling. Sphingolipid metabolites play distinct and complex roles in inflammatory signaling and will be discussed. We also review studies examining dietary sphingolipids and inflammation, derived from in vitro and rodent models, as well as human clinical trials. Dietary sphingolipids appear to influence inflammation-related chronic diseases through inhibiting intestinal lipid absorption, altering gut microbiota, activation of anti-inflammatory nuclear receptors, and neutralizing responses to inflammatory stimuli. The anti-inflammatory effects observed with consuming dietary sphingolipids are in contrast to the observation that most cellular sphingolipids play roles in augmenting inflammatory signaling. The relationship between dietary sphingolipids and low-grade chronic inflammation in metabolic disorders is complex and appears to depend on sphingolipid structure, digestion, and metabolic state of the organism. Further research is necessary to confirm the reported anti-inflammatory effects of dietary sphingolipids and delineate their impacts on endogenous sphingolipid metabolism.

  2. PET imaging of acute and chronic inflammation in living mice

    Energy Technology Data Exchange (ETDEWEB)

    Cao, Qizhen; Cai, Weibo; Li, Zi-Bo; Chen, Kai; He, Lina; Chen, Xiaoyuan [Stanford University School of Medicine, The Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X Program, Stanford, CA (United States); Li, Hui-Cheng; Hui, Mizhou [AmProtein Corporation, Camarillo, CA (United States)

    2007-11-15

    In this study, we evaluated the 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced acute and chronic inflammation in living mice by PET imaging of TNF-{alpha} and integrin {alpha}{sub v}{beta}{sub 3} expression. TPA was topically applied to the right ear of BALB/c mice every other day to create the inflammation model. {sup 64}Cu-DOTA-etanercept and {sup 64}Cu-DOTA-E{l_brace}E[c(RGDyK)]{sub 2}{r_brace}{sub 2} were used for PET imaging of TNF-{alpha} and integrin {alpha}{sub v}{beta}{sub 3} expression in both acute and chronic inflammation. Hematoxylin and eosin staining, ex vivo autoradiography, direct tissue sampling, and immunofluorescence staining were also performed to confirm the non-invasive PET imaging results. The ear thickness increased significantly and the TNF-{alpha} level more than tripled after a single TPA challenge. MicroPET imaging using {sup 64}Cu-DOTA-etanercept revealed high activity accumulation in the inflamed ear, reaching 11.1 {+-} 1.3, 13.0 {+-} 2.0, 10.9 {+-} 1.4, 10.2 {+-} 2.2%ID/g at 1, 4, 16, and 24 h post injection, respectively (n = 3). Repeated TPA challenges caused TPA-specific chronic inflammation and reduced {sup 64}Cu-DOTA-etanercept uptake due to lowered TNF-{alpha} expression. {sup 64}Cu-DOTA-E{l_brace}E[c(RGDyK)]{sub 2}{r_brace}{sub 2} uptake in the chronically inflamed ears (after four and eight TPA challenges) was significantly higher than in the control ears and those after one TPA challenge. Immunofluorescence staining revealed increased integrin {beta}{sub 3} expression, consistent with the non-invasive PET imaging results using {sup 64}Cu-DOTA-E{l_brace}E[c(RGDyK)]{sub 2}{r_brace}{sub 2} as an integrin {alpha}{sub v} {beta}{sub 3}-specific radiotracer. Biodistribution and autoradiography studies further confirmed the quantification capability of microPET imaging. Successful PET imaging of TNF- {alpha} expression in acute inflammation and integrin {alpha}{sub v} {beta}{sub 3} expression in chronic inflammation provides

  3. Chronic Inflammation and  T Cells

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    Nathan S Fay

    2016-05-01

    Full Text Available The epithelial tissues of the skin, lungs, reproductive tract, and intestines are the largest physical barriers the body has to protect against infection. Epithelial tissues are woven with a matrix of immune cells programmed to mobilize the host innate and adaptive immune responses. Included among these immune cells are  T cells that are unique in their TCR usage, location, and functions in the body. Stress reception by  T cells as a result of traumatic epithelial injury, malignancy, and/or infection induces  T cell activation. Once activated,  T cells function to repair tissue, induce inflammation, recruit leukocytes, and lyse cells. Many of these functions are mediated via the production of cytokines and growth factors upon  T cell activation. Pathogenesis of many chronic inflammatory diseases involve  T cells; some of which are exacerbated by their presence, while others are improved.  T cells require a delicate balance between their need for acute inflammatory mediators to function normally and the detrimental impact imparted by chronic inflammation. This review will focus on the recent progress made in understanding how epithelial  T cells influence the pathogenesis of chronic inflammatory diseases and how a balance between acute and chronic inflammation impacts  T cell function. Future studies will be important to understand how this balance is achieved.

  4. Parainflammation, chronic inflammation, and age-related macular degeneration.

    Science.gov (United States)

    Chen, Mei; Xu, Heping

    2015-11-01

    Inflammation is an adaptive response of the immune system to noxious insults to maintain homeostasis and restore functionality. The retina is considered an immune-privileged tissue as a result of its unique anatomic and physiologic properties. During aging, the retina suffers from a low-grade chronic oxidative insult, which sustains for decades and increases in level with advancing age. As a result, the retinal innate-immune system, particularly microglia and the complement system, undergoes low levels of activation (parainflammation). In many cases, this parainflammatory response can maintain homeostasis in the healthy aging eye. However, in patients with age-related macular degeneration, this parainflammatory response becomes dysregulated and contributes to macular damage. Factors contributing to the dysregulation of age-related retinal parainflammation include genetic predisposition, environmental risk factors, and old age. Dysregulated parainflammation (chronic inflammation) in age-related macular degeneration damages the blood retina barrier, resulting in the breach of retinal-immune privilege, leading to the development of retinal lesions. This review discusses the basic principles of retinal innate-immune responses to endogenous chronic insults in normal aging and in age-related macular degeneration and explores the difference between beneficial parainflammation and the detrimental chronic inflammation in the context of age-related macular degeneration. © Society for Leukocyte Biology.

  5. Chronic inflammation, insulin resistance, psoriasis - which have in common?

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    M. S. Rasin

    2016-01-01

    Full Text Available Psoriasis is recognized as system immune inflammatory disease at a certain genetic basis. It was found that psoriasis develops under the influence of chronic systemic inflammation low intensity (low grade inflammation that induced insulin resistance, and is one of the clinical forms of the Immune Metabolic Disease (IMD, along with atherosclerosis, hypertension, type 2 diabetes, obesity and many other diseases, whose tight relationship with psoriasis are installed. Knowledge of the etiology, pathogenesis and molecular mechanisms of communication with other clinical forms of the IMD opens up new ways of prevention and treatment of psoriasis. Please note that other diseases associated with psoriasis, occurring hidden, often have greater predictive value for the life and health of the patient than mild or moderate forms of psoriasis, and be not limited to ascertaining the diagnosis and symptomatic treatment and actively participate in prevention. Debated question of the application of funds, suppressing systemic inflammation and insulin resistance in the treatment of psoriasis.

  6. CXCR2 inhibition suppresses acute and chronic pancreatic inflammation.

    Science.gov (United States)

    Steele, Colin W; Karim, Saadia A; Foth, Mona; Rishi, Loveena; Leach, Joshua D G; Porter, Ross J; Nixon, Colin; Jeffry Evans, T R; Carter, C Ross; Nibbs, Robert J B; Sansom, Owen J; Morton, Jennifer P

    2015-09-01

    Pancreatitis is a significant clinical problem and the lack of effective therapeutic options means that treatment is often palliative rather than curative. A deeper understanding of the pathogenesis of both acute and chronic pancreatitis is necessary to develop new therapies. Pathological changes in pancreatitis are dependent on innate immune cell recruitment to the site of initial tissue damage, and on the coordination of downstream inflammatory pathways. The chemokine receptor CXCR2 drives neutrophil recruitment during inflammation, and to investigate its role in pancreatic inflammation, we induced acute and chronic pancreatitis in wild-type and Cxcr2(-/-) mice. Strikingly, Cxcr2(-/-) mice were strongly protected from tissue damage in models of acute pancreatitis, and this could be recapitulated by neutrophil depletion or by the specific deletion of Cxcr2 from myeloid cells. The pancreata of Cxcr2(-/-) mice were also substantially protected from damage during chronic pancreatitis. Neutrophil depletion was less effective in this model, suggesting that CXCR2 on non-neutrophils contributes to the development of chronic pancreatitis. Importantly, pharmacological inhibition of CXCR2 in wild-type mice replicated the protection seen in Cxcr2(-/-) mice in acute and chronic models of pancreatitis. Moreover, acute pancreatic inflammation was reversible by inhibition of CXCR2. Thus, CXCR2 is critically involved in the development of acute and chronic pancreatitis in mice, and its inhibition or loss protects against pancreatic damage. CXCR2 may therefore be a viable therapeutic target in the treatment of pancreatitis. © 2015 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

  7. Serum Autoantibodies in Chronic Prostate Inflammation in Prostate Cancer Patients

    Science.gov (United States)

    Schlick, Bettina; Massoner, Petra; Lueking, Angelika; Charoentong, Pornpimol; Blattner, Mirjam; Schaefer, Georg; Marquart, Klaus; Theek, Carmen; Amersdorfer, Peter; Zielinski, Dirk; Kirchner, Matthias; Trajanoski, Zlatko; Rubin, Mark A.; Müllner, Stefan; Schulz-Knappe, Peter; Klocker, Helmut

    2016-01-01

    Background Chronic inflammation is frequently observed on histological analysis of malignant and non-malignant prostate specimens. It is a suspected supporting factor for prostate diseases and their progression and a main cause of false positive PSA tests in cancer screening. We hypothesized that inflammation induces autoantibodies, which may be useful biomarkers. We aimed to identify and validate prostate inflammation associated serum autoantibodies in prostate cancer patients and evaluate the expression of corresponding autoantigens. Methods Radical prostatectomy specimens of prostate cancer patients (N = 70) were classified into high and low inflammation groups according to the amount of tissue infiltrating lymphocytes. The corresponding pre-surgery blood serum samples were scrutinized for autoantibodies using a low-density protein array. Selected autoantigens were identified in prostate tissue and their expression pattern analyzed by immunohistochemistry and qPCR. The identified autoantibody profile was cross-checked in an independent sample set (N = 63) using the Luminex-bead protein array technology. Results Protein array screening identified 165 autoantibodies differentially abundant in the serum of high compared to low inflammation patients. The expression pattern of three corresponding antigens were established in benign and cancer tissue by immunohistochemistry and qPCR: SPAST (Spastin), STX18 (Syntaxin 18) and SPOP (speckle-type POZ protein). Of these, SPAST was significantly increased in prostate tissue with high inflammation. All three autoantigens were differentially expressed in primary and/or castration resistant prostate tumors when analyzed in an inflammation-independent tissue microarray. Cross-validation of the inflammation autoantibody profile on an independent sample set using a Luminex-bead protein array, retrieved 51 of the significantly discriminating autoantibodies. Three autoantibodies were significantly upregulated in both screens, MUT

  8. Chronic inflammation and autoimmunity as risk factors for the development of chronic myelomonocytic leukemia?

    DEFF Research Database (Denmark)

    Elbæk, Mette Vestergaard; Sørensen, Anders Lindholm; Hasselbalch, Hans K

    2016-01-01

    . Controls were 231 unmatched chronic lymphatic leukemia (CLL) subjects diagnosed at one of the departments between 2003 and 2012. Subjects with a history of chronic inflammation or autoimmune disorders were retrieved and odds ratios (ORs) calculated. 16.1% of CMML subjects and 6.5% of CLL subjects presented......In this study, we investigate if chronic inflammation and autoimmunity might be related to the development of chronic myelomonocytic leukemia (CMML). Conducting a case-control study, we included 112 CMML subjects diagnosed at three hematological departments in Denmark between 2003 and 2013...... with a history of chronic inflammatory or autoimmune conditions. This was significantly associated with an increased risk of CMML (adjusted OR 3.24, 95% CI: 1.5–7.0). At individual levels, this association was statistically significant for polymyalgia rheumatica and ITP (p values

  9. Chronic inflammation-associated genomic instability paves the way for human esophageal carcinogenesis

    Science.gov (United States)

    Tian, Dongping; Lei, Zhijin; Chen, Donglin; Xu, Zexin; Su, Min

    2016-01-01

    Chronic inflammation is associated with increased risk of cancer development, whereas the link between chronic inflammation and esophageal carcinogenesis is still obscure heretofore. This study aimed to investigate the relationship between chronic inflammation and DNA damage, as well as the possible role of DNA damage in esophageal carcinogenic process. Endoscopic esophageal biopsies from 109 individuals from Chaoshan littoral, a high-risk region for esophageal squamous cell carcinoma (ESCC), were examined to evaluate the association between chronic inflammation and histological severity, while additional 204 esophageal non-tumor samples from patients with ESCC were collected. Immunohistochemistry was performed to detect the oxidative DNA damage and DNA double-strand breaks (DSBs). Significantly positive correlation was observed between degree of chronic inflammation and esophageal precursor lesions (rs = 0.37, P inflammation (rs = 0.21, P inflammation degree (P inflammation-associated genomic instability with esophageal carcinogenesis and suggest possibilities for early detection and intervention of esophageal carcinogenesis. PMID:27028857

  10. Adhesive capsulitis: An age related symptom of metabolic syndrome and chronic low-grade inflammation?

    Science.gov (United States)

    Pietrzak, Max

    2016-03-01

    Adhesive capsulitis (AC) is very poorly understood, particularly it's underlying etiology. Obesity and metabolic syndrome, which are strongly associated with chronic low grade inflammation, are becoming increasingly understood to underlie a raft of morbid states including upper limb pain syndromes, diabetes (DM), cardiovascular disease (CVD), cancer and central nervous system dysfunction and degeneration. Notwithstanding age, two of the strongest established risk factors for AC are DM and CVD. The hypothesis argues that similar to DM and CVD, the inflammation and capsular fibrosis seen in AC is precipitated by metabolic syndrome and chronic low grade inflammation. These pathophysiological mechanisms are highly likely to be perpetuated by upregulation of pro-inflammatory cytokine production, sympathetic dominance of autonomic balance, and neuro-immune activation. The hypothesis predicts and describes how these processes may etiologically underpin and induce each sub-classification of AC. An improved understanding of the etiology of AC may lead to more accurate diagnosis, improved management, treatment outcomes, and reduce or prevent pain, disability and suffering associated with the disease. The paper follows on with a discussion of similarities between the pathophysiology of AC to general systemic inflammatory control mechanisms whereby connective tissue (CT) fibrosis is induced as a storage depot for leukocytes and chronic inflammatory cells. The potential role of hyaluronic acid (HA), the primary component of the extracellular matrix (ECM) and CT, in the pathophysiology of AC is also discussed with potential treatment implications. Lastly, a biochemical link between physical and mental health through the ECM is described and the concept of a periventricular-limbic central driver of CT dysfunction is introduced. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Toxic stress, inflammation and symptomatology of chronic complications in diabetes.

    Science.gov (United States)

    Downs, Charles A; Faulkner, Melissa Spezia

    2015-05-15

    Diabetes affects at least 382 million people worldwide and the incidence is expected to reach 592 million by 2035. The incidence of diabetes in youth is skyrocketing as evidenced by a 21% increase in type 1 diabetes and a 30.5% increase in type 2 diabetes in the United States between 2001 and 2009. The effects of toxic stress, the culmination of biological and environmental interactions, on the development of diabetes complications is gaining attention. Stress impacts the hypothalamus-pituitary-adrenal axis and contributes to inflammation, a key biological contributor to the pathogenesis of diabetes and its associated complications. This review provides an overview of common diabetic complications such as neuropathy, cognitive decline, depression, nephropathy and cardiovascular disease. The review also provides a discussion of the role of inflammation and stress in the development and progression of chronic complications of diabetes, associated symptomatology and importance of early identification of symptoms of depression, fatigue, exercise intolerance and pain.

  12. Cardiovascular Disease and Chronic Inflammation in End Stage Kidney Disease

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    Sofia Zyga

    2013-01-01

    Full Text Available Background: Chronic Kidney Disease (CKD is one of the most severe diseases worldwide. In patients affected by CKD, a progressive destruction of the nephrons is observed not only in structuralbut also in functional level. Atherosclerosis is a progressive disease of large and medium-sized arteries. It is characterized by the deposition of lipids and fibrous elements and is a common complication of the uremic syndrome because of the coexistence of a wide range of risk factors. High blood pressure, anaemia, insulin resistance, inflammation, high oxidative stress are some of the most common factors that cause cardiovascular disease and atherogenesis in patients suffering from End Stage Kidney Disease (ESRD. At the same time, the inflammatory process constitutes a common element in the apparition and development of CKD. A wide range of possible causes can justify the development of inflammation under uremic conditions. Such causes are oxidative stress, oxidation, coexistentpathological conditions as well as factors that are due to renal clearance techniques. Patients in ESRD and coronary disease usually show increased acute phase products. Pre-inflammatory cytokines, such as IL-6 and TNF-a, and acute phase reactants, such as CRP and fibrinogen, are closely related. The treatment of chronic inflammation in CKD is of high importance for the development ofthe disease as well as for the treatment of cardiovascular morbidity.Conclusions: The treatment factors focus on the use of renin-angiotensic system inhibitors, acetylsalicylic acid, statins and anti-oxidant treatment in order to prevent the action of inflammatorycytokines that have the ability to activate the mechanisms of inflammation.

  13. Direct measurement of upper airway inflammation in children with chronic rhinosinusitis: implications for asthma.

    Science.gov (United States)

    Demirdag, Yesim Y; Ramadan, Hassan H

    2016-02-01

    Chronic rhinosinusitis (CRS) is a common heterogenous multifactorial disorder affecting children and adults. The exact mechanism is not completely understood. In this review, we aim to summarize our recent findings regarding etiologies and pathogenesis of CRS in children and review recent studies investigating inflammatory patterns in the upper airways in children and adults with CRS. There are only a few small studies measuring upper airway inflammation in children with CRS. These studies demonstrated more toward eosinophilic and T-cell driven inflammatory pattern. Cytokine patterns in upper airways seem to correlate with asthma symptoms in children with CRS. Adult studies demonstrate eosinophilic and Th-2 (T helper-1) driven inflammation in CRS with nasal polyps and Th-1 (T helper-2) driven inflammation in CRS without nasal polyps. Current knowledge about the characteristics of tissue inflammation in upper airways in children with CRS is limited. More studies are needed to better understand the pathogenesis and better define the subgroups of CRS. The findings of such studies will lead to identifying the biological targets to treat this condition.

  14. Mechanical stress as the common denominator between chronic inflammation, cancer and Alzheimer’s disease

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    Marcel eLevy Nogueira

    2015-09-01

    Full Text Available The pathogenesis of common diseases such as Alzheimer’s disease (AD and cancer are currently poorly understood. Inflammation is a common risk factor for cancer and AD. Recent data, provided by our group and from others, demonstrate that increased pressure and inflammation are synonymous. There is a continuous increase in pressure from inflammation to fibrosis and then cancer. This in line with the numerous papers reporting high interstitial pressure in cancer. But most authors focus on the role of pressure in the lack of delivery of chemotherapy in the center of the tumor. Pressure may also be a key factor in carcinogenesis. Increased pressure is responsible for oncogene activation and cytokine secretion. Accumulation of mechanical stress plays a key role in the development of diseases of old age such as cardiomyopathy, atherosclerosis and osteoarthritis. Growing evidence suggest also a possible link between mechanical stress in the pathogenesis of AD. The aim of this review is to describe environmental and endogenous mechanical factors possibly playing a pivotal role in the mechanism of chronic inflammation, AD and cancer.

  15. Biomarkers of inflammation in persons with chronic tetraplegia.

    Science.gov (United States)

    Radulovic, Miroslav; Bauman, William A; Wecht, Jill M; LaFountaine, Michael; Kahn, Nighat; Hobson, Joshua; Singh, Kamaldeep; Renzi, Christopher; Yen, Christina; Schilero, Gregory J

    2015-05-14

    In addition to lung volume restriction, individuals with chronic tetraplegia exhibit reduced airway caliber and bronchodilator responsiveness similar to persons with asthma. In asthma, airflow obstruction is closely linked to airway inflammation. Conversely, little is known regarding the airway inflammatory response in tetraplegia. To compare levels of biomarkers of inflammation in exhaled breath condensate (EBC) and serum in subjects with chronic tetraplegia, mild asthma, and able-bodied controls.Prospective, observational pilot study. Thirty-four subjects participated: tetraplegia (n = 12), asthma (n = 12), controls (n = 10). Biomarkers in EBC [8-isoprostane (8-IP), leukotriene B4 (LT-B4), prostaglandin E2 (PG-E2), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6)] and serum (8-IP, LT-B4, TNF-α, IL-6) were determined using commercially available EIA kits (Cayman Chemical Company, Ann Arbor, MI). Separate, one-way ANOVA with Bonferroni's post-hoc analyses were performed to determine group differences in demographic and dependent variables [EBC and serum biomarkers, fractional exhaled nitric oxide (FeNO), pulmonary function parameters, and specific airway conductance (sGaw)]. The tetraplegia group had significantly elevated 8-IP levels in EBC compared to the asthma (68 ± 38 versus 21 ± 13 pg ml(-1); p tetraplegia group (15 ± 6; p = 0.08). Levels of serum biomarkers did not differ significantly among groups. Through analysis of EBC, levels of 8-IP were significantly elevated compared to levels found in individuals with mild asthma and healthy controls. Further studies are needed to extend upon these preliminary findings that suggest the presence of airway inflammation in subjects with chronic tetraplegia, and how this relates to pulmonary dysfunction in this population.

  16. Chronic Lymphocytic Inflammation Specifies the Organ Tropism of Prions

    Science.gov (United States)

    Heikenwalder, Mathias; Zeller, Nicolas; Seeger, Harald; Prinz, Marco; Klöhn, Peter-Christian; Schwarz, Petra; Ruddle, Nancy H.; Weissmann, Charles; Aguzzi, Adriano

    2005-02-01

    Prions typically accumulate in nervous and lymphoid tissues. Because proinflammatory cytokines and immune cells are required for lymphoid prion replication, we tested whether inflammatory conditions affect prion pathogenesis. We administered prions to mice with five inflammatory diseases of the kidney, pancreas, or liver. In all cases, chronic lymphocytic inflammation enabled prion accumulation in otherwise prion-free organs. Inflammatory foci consistently correlated with lymphotoxin up-regulation and ectopic induction of FDC-M1+ cells expressing the normal cellular prion protein PrPC. By contrast, inflamed organs of mice lacking lymphotoxin-α or its receptor did not accumulate the abnormal isoform PrPSc, nor did they display infectivity upon prion inoculation. By expanding the tissue distribution of prions, chronic inflammatory conditions may act as modifiers of natural and iatrogenic prion transmission.

  17. Gastro-oesophageal reflux, eosinophilic airway inflammation and chronic cough.

    Science.gov (United States)

    Pacheco, Adalberto; Faro, Vicenta; Cobeta, Ignacio; Royuela, Ana; Molyneux, Ian; Morice, Alyn H

    2011-08-01

    Patients with eosinophilic airway inflammation (EAI) often show a therapeutic response to corticosteroids. Non-invasive methods of diagnosing EAI are potentially useful in guiding therapy, particularly in conditions such as chronic cough, for which corticosteroids may not be the first-line treatment. The value of exhaled nitric oxide (ENO) in the diagnosis of EAI was prospectively investigated in a cohort of 116 patients with chronic cough of varying aetiology. An optimum cut-off value was derived for differentiating between EAI and non-EAI causes of chronic cough. As the diagnosis was gastro-oesophageal reflux in 70 patients (60.3% of the total), the possible relationship between ENO and EAI in the presence or absence of reflux was subsequently investigated. The optimum value of ENO for differentiating EAI (32% of patients) from non-EAI causes of cough was 33 parts per billion (sensitivity 60.5%, specificity 84.6%). In the subgroup of patients with reflux, ENO was highly specific for the diagnosis of EAI (sensitivity 66%, specificity 100%). Conversely, in the patients without reflux, ENO did not discriminate between cough due to EAI or other causes (sensitivity 100%, specificity 28.9%). These results suggest that the presence or absence of reflux should be taken into consideration when interpreting ENO measurements in the diagnosis of chronic cough associated with EAI. © 2011 The Authors. Respirology © 2011 Asian Pacific Society of Respirology.

  18. Chronic psychological stress induces vascular inflammation in rabbits.

    Science.gov (United States)

    Lu, Xiao Ting; Liu, Yun Fang; Zhao, Li; Li, Wen Jing; Yang, Rui Xue; Yan, Fang Fang; Zhao, Yu Xia; Jiang, Fan

    2013-01-01

    Psychological stress is associated with a systemic inflammatory response. It is unclear, however, whether psychological stress contributes to vascular inflammation. Here, we examined the effects of unpredictable chronic mild stress (UCMS) on vascular inflammation in rabbits. One hundred rabbits were randomly divided into control and stress groups. UCMS was induced by a set of defined adverse conditions applied in a shuffled order for 4, 8, 12, or 16 weeks, and rabbits were killed 24 h after the end of the UCMS protocol. Expression of different inflammatory molecules was analyzed by real-time polymerase chain reaction, immunohistochemistry, or enzyme-linked immunosorbent assay. UCMS resulted in depression-like behaviors, decreased body weight gain, and hypertension with no significant effects on serum lipids. Aortic mRNA and protein expression for tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), monocyte chemoattractant protein-1 (MCP-1), macrophage migration inhibitory factor, and expression of intercellular adhesion molecule-1 (ICAM-1) protein were increased. UCMS increased circulating concentrations of corticosterone, TNF-α, and CRP throughout. Moreover, stress downregulated the expression of endothelial nitric oxide synthase. At 16 weeks of UCMS, macrophage infiltration and lipid accumulation in the subendothelial space were detected in the aorta. In cultured murine vascular smooth muscle cells, treatment with serum from stressed rabbits significantly increased phosphorylation of p38 and c-Jun N-terminal kinase (JNK), and upregulated expression of MCP-1 and ICAM-1 mRNAs, in which the effect was blunted by a TNF-α neutralizing antibody or p38 and JNK inhibitors. Our results indicate that chronic psychological stress induces vascular inflammation via TNF-α and p38/JNK pathways, which may contribute to the development of atherosclerosis.

  19. Bioactive Compounds Isolated from Microalgae in Chronic Inflammation and Cancer

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    Elena Talero

    2015-09-01

    Full Text Available The risk of onset of cancer is influenced by poorly controlled chronic inflammatory processes. Inflammatory diseases related to cancer development include inflammatory bowel disease, which can lead to colon cancer, or actinic keratosis, associated with chronic exposure to ultraviolet light, which can progress to squamous cell carcinoma. Chronic inflammatory states expose these patients to a number of signals with tumorigenic effects, including nuclear factor kappa B (NF-κB and mitogen-activated protein kinases (MAPK activation, pro-inflammatory cytokines and prostaglandins release and ROS production. In addition, the participation of inflammasomes, autophagy and sirtuins has been demonstrated in pathological processes such as inflammation and cancer. Chemoprevention consists in the use of drugs, vitamins, or nutritional supplements to reduce the risk of developing or having a recurrence of cancer. Numerous in vitro and animal studies have established the potential colon and skin cancer chemopreventive properties of substances from marine environment, including microalgae species and their products (carotenoids, fatty acids, glycolipids, polysaccharides and proteins. This review summarizes the main mechanisms of actions of these compounds in the chemoprevention of these cancers. These actions include suppression of cell proliferation, induction of apoptosis, stimulation of antimetastatic and antiangiogenic responses and increased antioxidant and anti-inflammatory activity.

  20. Bioactive Compounds Isolated from Microalgae in Chronic Inflammation and Cancer

    Science.gov (United States)

    Talero, Elena; García-Mauriño, Sofía; Ávila-Román, Javier; Rodríguez-Luna, Azahara; Alcaide, Antonio; Motilva, Virginia

    2015-01-01

    The risk of onset of cancer is influenced by poorly controlled chronic inflammatory processes. Inflammatory diseases related to cancer development include inflammatory bowel disease, which can lead to colon cancer, or actinic keratosis, associated with chronic exposure to ultraviolet light, which can progress to squamous cell carcinoma. Chronic inflammatory states expose these patients to a number of signals with tumorigenic effects, including nuclear factor kappa B (NF-κB) and mitogen-activated protein kinases (MAPK) activation, pro-inflammatory cytokines and prostaglandins release and ROS production. In addition, the participation of inflammasomes, autophagy and sirtuins has been demonstrated in pathological processes such as inflammation and cancer. Chemoprevention consists in the use of drugs, vitamins, or nutritional supplements to reduce the risk of developing or having a recurrence of cancer. Numerous in vitro and animal studies have established the potential colon and skin cancer chemopreventive properties of substances from marine environment, including microalgae species and their products (carotenoids, fatty acids, glycolipids, polysaccharides and proteins). This review summarizes the main mechanisms of actions of these compounds in the chemoprevention of these cancers. These actions include suppression of cell proliferation, induction of apoptosis, stimulation of antimetastatic and antiangiogenic responses and increased antioxidant and anti-inflammatory activity. PMID:26437418

  1. Neurological and cellular regulation of visceral hypersensitivity induced by chronic stress and colonic inflammation in rats

    Science.gov (United States)

    Chen, Jinghong; Winston, John H.; Sarna, Sushil K.

    2013-01-01

    The role of inflammation in inducing visceral hypersensitivity (VHS) in ulcerative colitis patients remains unknown. We tested the hypothesis that acute ulcerative colitis-like inflammation does not induce VHS. However, it sets up molecular conditions such that chronic stress following inflammation exaggerates single unit afferent discharges to colorectal distension. We used dextran sodium sulfate (DSS) to induce ulcerative colitis-like inflammation and a 9-day heterotypic chronic stress protocol in rats. DSS upregulated Nav1.8 mRNA in colon-responsive DRG neurons, TRPV1 in colonic muscularis externae (ME) and BDNF in spinal cord without affecting the spike frequency in spinal afferents or VMR to CRD. By contrast, chronic stress did not induce inflammation but it downregulated Kv1.1 and Kv1.4 mRNA in DRG neurons, and upregulated TRPA1 and NGF in ME, which mediated the increase of spike frequency and VMR to CRD. Chronic stress following inflammation exacerbated spike frequency in spinal afferent neurons. TRPA1 antagonist suppressed the sensitization of afferent neurons. DSS-inflammation did not affect the composition or excitation thresholds of low-threshold and high-threshold fibers. Chronic stress following inflammation increased the percent composition of high-threshold fibers and lowered the excitation threshold of both types of fibers. We conclude that not all types of inflammation induce VHS, whereas chronic stress induces VHS in the absence of inflammation. PMID:23806714

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

    NARCIS (Netherlands)

    Pruimboom, Leo; Raison, Charles L.; Muskiet, Frits A. J.

    2015-01-01

    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

  3. Green tea polyphenols avert chronic inflammation-induced myocardial fibrosis of female rats

    Science.gov (United States)

    Objective: Green tea proposes anti-inflammatory properties which may attenuate chronic inflammation-induced fibrosis of vessels. This study evaluated whether green tea polyphenols (GTP) can avert fibrosis or vascular disruption along with mechanisms in rats with chronic inflammation. Treatments: Fo...

  4. Association of current smoking with airway inflammation in chronic obstructive pulmonary disease and asymptomatic smokers

    NARCIS (Netherlands)

    Willemse, BWM; ten Hacken, NHT; Rutgers, B; Postma, DS; Timens, W

    2005-01-01

    Background: Inflammation in the airways and lung parenchyma underlies fixed airway obstruction in chronic obstructive pulmonary disease. The exact role of smoking as promoting factor of inflammation in chronic obstructive pulmonary disease is not clear, partly because studies often do not

  5. Salt Intake Is Associated with Inflammation in Chronic Heart Failure

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    Alper Azak

    2015-09-01

    Full Text Available Background: Chronic Heart Failure (CHF is highly prevalent and is associated with high morbidity and mortality rates. It has been well established that excessive intake of sodium chloride (salt induced hypertension in some populations. Although salt seems to induce cardiovascular diseases through elevation of blood pressure, it has also been indicated that salt can induce cardiovascular diseases independently from blood pressure elevation. Objectives: The present study aimed to evaluate the association between salt consumption and inflammation in CHF patients. Patients and Methods: This study was conducted on 86 patients between 18 and 65 years old who were diagnosed with New York Heart Association (NYHA functional class I and II heart failure. Salt intake was calculated by using 24 hour urine sodium excretion. Besides, the association between inflammation and daily salt intake was evaluated regarding C - reactive protein (CPR, High sensitive CRP (HsCPR, Erythrocyte Sedimentation Rate (ESR, and ferritin and fibrinogen levels using Pearson correlation analysis. Results: Our results showed a statistically significant difference between the low (n = 41 and high (n = 45 salt intake groups in terms of serum HsCRP levels (5.21 ± 2.62 vs. 6.36 ± 2.64 (P < 0.048. Additionally, a significant correlation was observed between the amount of salt consumption and HsCRP levels. In this study, daily salt consumption of the enrolled patients was 8.53 gram/day. The medications and even the blood pressures were similar in the two groups, but daily pill count, prevalence of hypertension, and coronary heart disease were higher in the high salt intake group; however, the differences were not statistically significant (P = 0.065. Also, no significant difference was observed between the groups concerning the inflammation markers, such as CRP, ESR, ferritin, and fibrinogen. Conclusions: Neurohumoral and inflammatory factors are thought to contribute to high mortality

  6. Angiogenesis: From Chronic Liver Inflammation to Hepatocellular Carcinoma

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    Paloma Sanz-Cameno

    2010-01-01

    Full Text Available Recently, new information relating to the potential relevance of chronic hepatic inflammation to the development and progression of hepatocellular carcinoma (HCC has been generated. Persistent hepatocellular injury alters the homeostatic balance within the liver; deregulation of the expression of factors involved in wound healing may lead to the evolution of dysplastic lesions into transformed nodules. Progression of such nodules depends directly on the development and organization of a vascular network, which provides the nutritional and oxygen requirements to an expanding nodular mass. Angiogenic stimulation promotes intense structural and functional changes in liver architecture and physiology, in particular, it facilitates transformation of dysplasia to nodular lesions with carcinogenic potential. HCC depends on the growth and spreading of vessels throughout the tumor. Because these vascular phenomena correlate with disease progression and prognosis, therapeutic strategies are being developed that focus on precluding vascular expansion in these tumors. Accordingly, an in-depth study of factors that promote and support pathological angiogenesis in chronic hepatic diseases may provide insights into methods of preventing the development of HCC and/or stimulating the regression of established HCC.

  7. Blood Biomarkers of Chronic Inflammation in Gulf War Illness.

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    Gerhard J Johnson

    Full Text Available More than twenty years following the end of the 1990-1991 Gulf War it is estimated that approximately 300,000 veterans of this conflict suffer from an unexplained chronic, multi-system disorder known as Gulf War Illness (GWI. The etiology of GWI may be exposure to chemical toxins, but it remains only partially defined, and its case definition is based only on symptoms. Objective criteria for the diagnosis of GWI are urgently needed for diagnosis and therapeutic research.This study was designed to determine if blood biomarkers could provide objective criteria to assist diagnosis of GWI.A surveillance study of 85 Gulf War Veteran volunteers identified from the Department of Veterans Affairs Minnesota Gulf War registry was performed. All subjects were deployed to the Gulf War. Fifty seven subjects had GWI defined by CDC criteria, and 28 did not have symptomatic criteria for a diagnosis of GWI. Statistical analyses were performed on peripheral blood counts and assays of 61 plasma proteins using the Mann-Whitney rank sum test to compare biomarker distributions and stepwise logistic regression to formulate a diagnostic model.Lymphocyte, monocyte, neutrophil, and platelet counts were higher in GWI subjects. Six serum proteins associated with inflammation were significantly different in GWI subjects. A diagnostic model of three biomarkers-lymphocytes, monocytes, and C reactive protein-had a predicted probability of 90% (CI 76-90% for diagnosing GWI when the probability of having GWI was above 70%.The results of the current study indicate that inflammation is a component of the pathobiology of GWI. Analysis of the data resulted in a model utilizing three readily measurable biomarkers that appears to significantly augment the symptom-based case definition of GWI. These new observations are highly relevant to the diagnosis of GWI, and to therapeutic trials.

  8. Stunting is characterized by chronic inflammation in Zimbabwean infants.

    Directory of Open Access Journals (Sweden)

    Andrew J Prendergast

    and that low-grade chronic inflammation may impair infant growth.

  9. Chronic Inflammation in Colorectal Carcinogenesis: Role of Inflammatory Mediators, Intestinal Microbes, and Chemoprevention Potency

    OpenAIRE

    Tedja, Irwin; Abdullah, Murdani

    2013-01-01

    Colorectal carcinogenesis is a multi-factorial process which involves accumulation of genetic defect, protein modification, and cell interaction with matrix in colonic epithelial cells. Chronic inflammation is suspected to play role in carcinogenesis by inhibiting apoptosis, impairing DNA, and chronically stimulating mucosal proliferation. Alteration in intestinal microbes' population, either in one particular species or in overall composition, may also cause chronic inflammation which increa...

  10. Chronic inflammation of the vagina: treatment and relationship to autoimmunity.

    Science.gov (United States)

    Thomson, John C

    2005-07-01

    To investigate noninfective, symptomatic, chronic inflammation (CI) of the vaginal mucosa to determine its prevalence and immunologic basis and to initiate an immunologic approach to treatment and assess the response. A prospective, observational, clinical study of 55 women with dyspareunia and/or discharge of vaginal mucosal origin. Vaginal biopsies and immune investigations were carried out. Treatment was instituted utilizing immune-modifying agents. The prevalence of CI of the vagina in symptom-free women was 0-4.3% and in the symptomatic group, 89%. Systemic immune activation was demonstrated in 43 of the 55, with 21 suffering from an autoimmune disease or a condition in which immune activation plays a part, including endometriosis in 20. Thirty-one were treated; intravaginal hydrocortisone acetate 10% foam was given in 24, giving full relief in 14 and inadequate relief in 10. Hydroxychloroquine, an immune-modifying, antirheumatic drug, was added and largely gave relief in these 10. Hydroxychloroquine alone was given in 4 and was effective in 3. Overall, immune-modifying drugs were successful in 97%. CI of the vaginal mucosa stems from local immune activation and is generally associated with evidence of other immune abnormalities, including autoimmune diseases and disorders in which immune activation play a part, including endometriosis. It can be successfully treated by immune modification.

  11. Age-Related Macular Degeneration in the Aspect of Chronic Low-Grade Inflammation (Pathophysiological ParaInflammation

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    Małgorzata Nita

    2014-01-01

    Full Text Available The products of oxidative stress trigger chronic low-grade inflammation (pathophysiological parainflammation process in AMD patients. In early AMD, soft drusen contain many mediators of chronic low-grade inflammation such as C-reactive protein, adducts of the carboxyethylpyrrole protein, immunoglobulins, and acute phase molecules, as well as the complement-related proteins C3a, C5a, C5, C5b-9, CFH, CD35, and CD46. The complement system, mainly alternative pathway, mediates chronic autologous pathophysiological parainflammation in dry and exudative AMD, especially in the Y402H gene polymorphism, which causes hypofunction/lack of the protective complement factor H (CFH and facilitates chronic inflammation mediated by C-reactive protein (CRP. Microglial activation induces photoreceptor cells injury and leads to the development of dry AMD. Many autoantibodies (antibodies against alpha beta crystallin, alpha-actinin, amyloid, C1q, chondroitin, collagen I, collagen III, collagen IV, elastin, fibronectin, heparan sulfate, histone H2A, histone H2B, hyaluronic acid, laminin, proteoglycan, vimentin, vitronectin, and aldolase C and pyruvate kinase M2 and overexpression of Fcc receptors play role in immune-mediated inflammation in AMD patients and in animal model. Macrophages infiltration of retinal/choroidal interface acts as protective factor in early AMD (M2 phenotype macrophages; however it acts as proinflammatory and proangiogenic factor in advanced AMD (M1 and M2 phenotype macrophages.

  12. Patterns of chronic inflammation in extensively treated patients with arachnoiditis and chronic intractable pain.

    Science.gov (United States)

    Bilello, John A; Tennant, Forest S

    2017-01-01

    To use biomarkers to gain insight into and gauge the residual (post-treatment) level of inflammation in two groups of intensively treated patients with severe chronic pain. Three study groups were analyzed, and included: (i) patients (n = 90) with chronic intractable pain (CIP), (ii) patients (n = 26) with chronic pain and MRI-documented arachnoiditis (ARC) and (iii) normal subjects without a diagnosis of chronic pain (n = 86). We determined and compared the serum concentrations of Alpha-1 Antitrypsin (A1AT), Myeloperoxidase (MPO) and soluble Tumor Necrosis Factor receptor type 2 (sTNFR2) in each of the patient populations studied. Patients treated for ARC or CIP had higher serum levels of A1AT and MPO than normal untreated subjects without a diagnosis of chronic pain. ARC patients had an A1AT mean serum concentration of 167.9 ± 41.9 mg/dL as compared to 148.9 ± 35.2 mg/dL for normal subjects (p = 0.023). CIP patients had the highest mean serum A1AT level 183.6 ± 39.2 mg/dL with p values of pain, sites of neuroinflammation elaborate MPO and other inflammatory factors which may not be completely cleared from the system despite extensive and complex treatment regimens.

  13. The role of physiological elements in the future therapies of rheumatoid arthritis. II. The relevance of energy redistribution in the process of chronic inflammation.

    Science.gov (United States)

    Gajewski, Michał; Rzodkiewicz, Przemysław; Wojtecka-Łukasik, Elżbieta

    2015-01-01

    The reasons for development of chronic inflammation are complex and not fully understood. One of the factors affecting the prolongation of inflammation is changes in cell metabolism, occurring at the center of the inflammatory process. In chronic inflammation there is an imbalance between the processes of storage and consumption of energy reserves. Hypoxia that is a consequence of edema results in transition of white blood cells to anaerobic metabolism. Neutrophils, lymphocytes and macrophages produce active oxygen metabolites which on one hand facilitate the elimination of pathogens, and on the other hand, can cause damage to healthy cells located in the inflamed tissue. In this paper, we discuss the importance of disturbed redistribution of energy as one of the main reasons for transformation of the acute inflammatory process into the chronic one.

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

    Directory of Open Access Journals (Sweden)

    Leo Pruimboom

    2015-01-01

    Full Text Available 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, and by doing so would improve human health.

  15. Ab interno laser sclerostomy in aphakic patients with glaucoma and chronic inflammation.

    Science.gov (United States)

    Wilson, R P; Javitt, J C

    1990-08-15

    Five patients with aphakia, glaucoma, and chronic inflammation were treated with ab interno sclerostomy by using the continuous wave Nd:YAG laser focused through a sapphire probe. After a follow-up period of 24 to 28 months, three of five patients had good intraocular pressure control. The sclerostomy failed in one patient when it was occluded by vitreous. The second failure was attributed to closure of the sclerostomy because of chronic intraocular inflammation.

  16. Physical Activity to Reduce Systemic Inflammation Associated With Chronic Pain and Obesity: A Narrative Review.

    Science.gov (United States)

    Paley, Carole A; Johnson, Mark I

    2016-04-01

    The increasing prevalence of chronic pain and obesity has significant health and cost implications for economies in the developed and developing world. Evidence suggests that there is a positive correlation between obesity and chronic pain and the link between them is thought to be systemic inflammation. The aim of this narrative review was to explore the physiological links between chronic musculoskeletal pain and obesity and to consider the potential role of regular physical activity in providing a means of managing obesity-related chronic pain. Systemic inflammation, mechanical overload, and autonomic dysfunction are associated with increased prevalence and severity of chronic pain in individuals with obesity. It has been proposed, therefore, that interventions that target systemic inflammation could help to reduce chronic pain in obese individuals. Reduction in abdominal fat has been shown to alleviate pain and reduce the systemic markers of inflammation that contribute to chronic pain. Interventions that include exercise prescription have been shown to reduce both abdominal fat and systemic inflammation. Furthermore, exercise is also known to reduce pain perception and improve mental health and quality of life that also improves pain outcomes. However, adherence to formal exercise prescription is poor and therefore exercise programmes should be tailored to the interests, needs, and abilities of individuals to reduce attrition.

  17. Chronic Inflammation-Related HPV: A Driving Force Speeds Oropharyngeal Carcinogenesis.

    Directory of Open Access Journals (Sweden)

    Xin Liu

    Full Text Available Oropharyngeal squamous cell carcinoma (OPSCC has been known to be a highly aggressive disease associated with human papilloma virus (HPV infection. To investigate the relationship between HPV and chronic inflammation in oropharyngeal carcinogenesis, we collected 140 oral mucous fresh specimens including 50 OPSCC patients, 50 cancer in situ, 30 precancerous lesions, and 10 normal oral mucous. Our data demonstrated that there was a significantly higher proportion of severe chronic inflammation in dysplastic epithelia in comparison with that in normal tissues (P<0.001. The positive rate of HPV 16 was parallel with the chronic inflammation degrees from mild to severe inflammation (P<0.05. The positive rate of HPV 16 was progressively improved with the malignant progression of oral mucous (P<0.05. In addition, CD11b+ LIN- HLA-DR-CD33+ MDSCs were a critical cell population that mediates inflammation response and immune suppression in HPV-positive OPSCC. These indicated that persistent chronic inflammation-related HPV infection might drive oropharyngeal carcinogenesis and MDSCs might pay an important role during this process. Thus, a combination of HPV infection and inflammation expression might become a helpful biomedical marker to predict oropharyngeal carcinogenesis.

  18. [Partsch's chronic granulomatous inflammation, the cutaneous manifestation of a dental cause].

    Science.gov (United States)

    Buch, R S R; Fischer, B; Kleis, W K G; Reichert, T E

    2003-08-01

    Dentogenous inflammatory diseases can lead to typical dermatological facial symptoms with formation of cutaneous sinuses. Partsch's chronic granulomatous inflammation can result from conducted inflammation of a nonvital tooth via a chronic apical inflammation. In this rare disease, the granulomatous tissue perforates the bone, channels through the overlying skin, and drains via cutaneous or oral sinuses. A frequent localization of the cutaneous sinus is the skin inferior to the body of the mandible, and it is caused by an inflammation of the lower molars. Treatment consists of identifying the responsible teeth and eliminating the focus of infection. Chronically progressive periradicular granuloma and/or radicular cysts can be present with impressive dermatological symptoms. Therefore, X-ray examinations are necessary to exclude possible dentogenic causes in cases of badly healing processes of the face or neck.

  19. Chronic Inflammation in an Anophthalmic Socket due to a Room Temperature Vulcanized Silicone Implant

    Directory of Open Access Journals (Sweden)

    Alicia Galindo-Ferreiro

    2016-04-01

    Full Text Available Two case reports are used to illustrate the signs and symptoms, complications and treatments of chronic socket inflammation due to intraorbital implants. The ophthalmic examination, surgeries and treatments are documented. Two anophthalmic cases that underwent enucleation and multiple orbital surgeries to enhance the anophthalmic socket volume developed pain, intense discharge and contracted cavities with chronic inflammation in the socket which was nonresponsive to medical therapy. Computed tomography indicated a hypodense foreign body in both cases causing an intense inflammatory reaction. The implants were removed by excisional surgery and a room temperature vulcanized silicone implant was retrieved in both cases. Socket inflammation resolved in both cases after implant removal. An intraorbital inflammatory reaction against an intraorbital implant can cause chronic socket inflammation in patients with a history of multiple surgeries. Diagnosis requires imaging and the definitive treatment is implant removal.

  20. Chronic inflammation as a promotor of mutagenesis in essential thrombocythemia, polycythemia vera and myelofibrosis. A human inflammation model for cancer development?

    DEFF Research Database (Denmark)

    Hasselbalch, Hans K

    2013-01-01

    The Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) are acquired stem cell neoplasms, in which a stem cell lesion induces an autonomous proliferative advantage. In addition to the JAK2V617 mutation several other mutations have been described. Recently chronic inflammation has been......-risk microenvironment for induction of mutations due to the persistent inflammation-induced oxidative damage to DNA in hematopoietic cells. Alterations in the epigenome induced by the chronic inflammatory drive may likely elicit a "epigenetic switch" promoting persistent inflammation. The perspectives of chronic...

  1. Cigarette Smoke-Induced Collagen Destruction; Key to Chronic Neutrophilic Airway Inflammation?

    NARCIS (Netherlands)

    Overbeek, Saskia A.; Braber, Saskia; Koelink, Pim J.; Henricks, Paul A. J.; Mortaz, Esmaeil; Loi, Adele T. LoTam; Jackson, Patricia L.; Garssen, Johan; Wagenaar, Gerry T. M.; Timens, Wim; Koenderman, Leo; Blalock, J. Edwin; Kraneveld, Aletta D.; Folkerts, Gert

    2013-01-01

    Background: Cigarette smoking induces inflammatory responses in all smokers and is the major risk factor for lung disease such as chronic obstructive pulmonary disease (COPD). In this progressive disease, chronic inflammation in the lung contributes to lung tissue destruction leading to the

  2. Inflammation and premature aging in advanced chronic kidney disease.

    Science.gov (United States)

    Kooman, Jeroen P; Dekker, Marijke J; Usvyat, Len A; Kotanko, Peter; van der Sande, Frank M; Schalkwijk, Casper G; Shiels, Paul G; Stenvinkel, Peter

    2017-10-01

    Systemic inflammation in end-stage renal disease is an established risk factor for mortality and a catalyst for other complications, which are related to a premature aging phenotype, including muscle wasting, vascular calcification, and other forms of premature vascular disease, depression, osteoporosis, and frailty. Uremic inflammation is also mechanistically related to mechanisms involved in the aging process, such as telomere shortening, mitochondrial dysfunction, and altered nutrient sensing, which can have a direct effect on cellular and tissue function. In addition to uremia-specific causes, such as abnormalities in the phosphate-Klotho axis, there are remarkable similarities between the pathophysiology of uremic inflammation and so-called "inflammaging" in the general population. Potentially relevant, but still somewhat unexplored in this respect, are abnormal or misplaced protein structures, as well as abnormalities in tissue homeostasis, which evoke danger signals through damage-associated molecular patterns, as well as the senescence-associated secretory phenotype. Systemic inflammation, in combination with the loss of kidney function, can impair the resilience of the body to external and internal stressors by reduced functional and structural tissue reserves, and by impairing normal organ crosstalk, thus providing an explanation for the greatly increased risk of homeostatic breakdown in this population. In this review, the relationship between uremic inflammation and a premature aging phenotype, as well as potential causes and consequences, are discussed. Copyright © 2017 the American Physiological Society.

  3. Contribution of inflammation to vascular disease in chronic kidney disease patients

    International Nuclear Information System (INIS)

    Suliman, Mohamed E.; Stenvinkel, P.

    2008-01-01

    Chronic kidney disease (CKD) is characterized by an exceptionally high mortality rate, much of which results from cardiovascular disease (CVD). Chronic low-grade inflammation, as evidenced by increased levels of pro-inflammatory cytokines and C-reactive protein (CRP), is a common feature of CKD and may cause atherosclerotic CVD through various pathogenetic mechanisms. Evidence suggests that persistent inflammation may also be a risk factor for progression of CKD, which may result in a vicious inflammation-driven circle. The causes of inflammation in CKD are multifactorial. The influence of various comorbidities may contribute to inflammation in the setting of progressive loss of renal function. Available data suggest that pro-inflammatory cytokines also play a central role in the genesis of the metabolic syndrome. There is a lack of epidemiological data on the prevalence and consequences of inflammation in relation to protein-energy wasting (PEW) and CVD in CKD patients from developing countries. The westernization of nutritional intakes and changes of life style besides the high prevalence of chronic infections in developing countries are possible additive contributors to a high prevalence of inflammation, PEW and CVD among CKD patients. Also, genetic differences may affect inflammatory responses and nutritional status and thus the susceptibility to CVD in different regions. (author)

  4. IL-17 is not essential for inflammation and chronic pelvic pain development in an experimental model of chronic prostatitis/chronic pelvic pain syndrome.

    Science.gov (United States)

    Motrich, Ruben D; Breser, María L; Sánchez, Leonardo R; Godoy, Gloria J; Prinz, Immo; Rivero, Virginia E

    2016-03-01

    Pain and inflammation in the absence of infection are hallmarks in chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS) patients. The etiology of CP/CPPS is unclear, and autoimmunity has been proposed as a cause. Experimental autoimmune prostatitis (EAP) models have long been used for studying CP/CPPS. Herein, we studied prostate inflammation induction and chronic pelvic pain development in EAP using IL-12p40-KO, IL-4-KO, IL-17-KO, and wild-type (C57BL/6) mice. Prostate antigen (PAg) immunization in C57BL/6 mice induced specific Th1 and Th17 immune responses and severe prostate inflammation and cell infiltration, mainly composed of CD4 T cells and macrophages. Moreover, chronic pelvic pain was evidenced by increased allodynia responses. In immunized IL-17-KO mice, the presence of a prominent PAg-specific Th1 immune response caused similar prostate inflammation and chronic pelvic pain. Furthermore, markedly high PAg-specific Th1 immune responses, exacerbated prostate inflammation, and chronic pelvic pain were detected in immunized IL-4-KO mice. Conversely, immunized IL-12p40-KO mice developed PAg-specific Th2 immune responses, characterized by high IL-4 secretion and neither infiltration nor damage in the prostate. As observed in wild-type control animals, IL12p40-KO mice did not evidence tactile allodynia responses. Our results suggest that, as in patients, chronic pelvic pain is a consequence of prostate inflammation. After PAg immunization, a Th1-associated immune response develops and induces prostate inflammation and chronic pelvic pain. The absence of Th1 or Th2 cytokines, respectively, diminishes or enhances EAP susceptibility. In addition, IL-17 showed not to be essential for pathology induction and chronic pelvic pain development.

  5. Immune biomarkers for chronic inflammation related complications in non-cancerous and cancerous diseases.

    Science.gov (United States)

    Meirow, Yaron; Baniyash, Michal

    2017-08-01

    Chronic inflammation arising in a diverse range of non-cancerous and cancerous diseases, dysregulates immunity and exposes patients to a variety of complications. These include immunosuppression, tissue damage, cardiovascular diseases and more. In cancer, chronic inflammation and related immunosuppression can directly support tumor growth and dramatically reduce the efficacies of traditional treatments, as well as novel immune-based therapies, which require a functional immune system. Nowadays, none of the immune biomarkers, regularly used by clinicians can sense a developing chronic inflammation, thus complications can only be detected upon their appearance. This review focuses on the necessity for such immune status biomarkers, which could predict complications prior to their appearance. Herein we bring examples for the use of cellular and molecular biomarkers in diagnosis, prognosis and follow-up of patients suffering from various cancers, for prediction of response to immune-based anti-cancer therapy and for prediction of cardiovascular disease in type 2 diabetes patients. Monitoring such biomarkers is expected to have a major clinical impact in addition to unraveling of the entangled complexity underlying dysregulated immunity in chronic inflammation. Thus, newly discovered biomarkers and those that are under investigation are projected to open a new era towards combating the silent damage induced by chronic inflammation.

  6. Hypothalamic inflammation and food intake regulation during chronic illness

    NARCIS (Netherlands)

    Dwarkasing, J.T.; Marks, D.L.; Witkamp, R.F.; Norren, van K.

    2016-01-01

    Anorexia is a common symptom in chronic illness. It contributes to malnutrition and strongly affects survival and quality of life. A common denominator of many chronic diseases is an elevated inflammatory status, which is considered to play a pivotal role in the failure of food-intake regulating

  7. N-acetylcysteine (NAC) ameliorates Epstein-Barr virus latent membrane protein 1 induced chronic inflammation.

    Science.gov (United States)

    Gao, Xiao; Lampraki, Eirini-Maria; Al-Khalidi, Sarwah; Qureshi, Muhammad Asif; Desai, Rhea; Wilson, Joanna Beatrice

    2017-01-01

    Chronic inflammation results when the immune system responds to trauma, injury or infection and the response is not resolved. It can lead to tissue damage and dysfunction and in some cases predispose to cancer. Some viruses (including Epstein-Barr virus (EBV)) can induce inflammation, which may persist even after the infection has been controlled or cleared. The damage caused by inflammation, can itself act to perpetuate the inflammatory response. The latent membrane protein 1 (LMP1) of EBV is a pro-inflammatory factor and in the skin of transgenic mice causes a phenotype of hyperplasia with chronic inflammation of increasing severity, which can progress to pre-malignant and malignant lesions. LMP1 signalling leads to persistent deregulated expression of multiple proteins throughout the mouse life span, including TGFα S100A9 and chitinase-like proteins. Additionally, as the inflammation increases, numerous chemokines and cytokines are produced which promulgate the inflammation. Deposition of IgM, IgG, IgA and IgE and complement activation form part of this process and through genetic deletion of CD40, we show that this contributes to the more tissue-destructive aspects of the phenotype. Treatment of the mice with N-acetylcysteine (NAC), an antioxidant which feeds into the body's natural redox regulatory system through glutathione synthesis, resulted in a significantly reduced leukocyte infiltrate in the inflamed tissue, amelioration of the pathological features and delay in the inflammatory signature measured by in vivo imaging. Reducing the degree of inflammation achieved through NAC treatment, had the knock on effect of reducing leukocyte recruitment to the inflamed site, thereby slowing the progression of the pathology. These data support the idea that NAC could be considered as a treatment to alleviate chronic inflammatory pathologies, including post-viral disease. Additionally, the model described can be used to effectively monitor and accurately measure

  8. One in vitro model for visceral adipose-derived fibroblasts in chronic inflammation

    International Nuclear Information System (INIS)

    Yue Guiping; Du Lirui; Xia Tao; He Xianhui; Qiu Huan; Xu Lihui; Chen Xiaodong; Feng Shengqiu; Yang Zaiqing

    2005-01-01

    One pathogenesis of the obesity-associated complications is that consistent with increased body fat mass, the elevation of adipose tissue-derived cytokines inflicts a low-grade chronic inflammation, which ultimately leads to metabolic disorders. Adipocytes and macrophages in visceral adipose (VA) have been confirmed to contribute to the chronic inflammation; however, the role of the resident fibroblasts is still unknown. We established one VA fibroblast cell line, termed VAFC. Morphological analysis indicated that there were large numbers of pits at the cell plasma membrane. In vitro VAFC cells promoted bone marrow cells to differentiate into macrophages and protected them from apoptosis in the serum-free conditions. Additionally, they also interfered in lymphocytes proliferation. On the basis of these results, this cell line might be an in vitro model for understanding the role of adipose-derived fibroblasts in obesity-associated chronic inflammation

  9. Patients with chronic obstructive pulmonary disease and chronically colonized with Haemophilus influenzae during stable disease phase have increased airway inflammation.

    Science.gov (United States)

    Tufvesson, Ellen; Bjermer, Leif; Ekberg, Marie

    2015-01-01

    Some patients with chronic obstructive pulmonary disease (COPD) show increased airway inflammation and bacterial colonization during stable phase. The aim of this study was to follow COPD patients and investigate chronic colonization with pathogenic bacteria during stable disease phase, and relate these findings to clinical parameters, inflammatory pattern, lung function, and exacerbations. Forty-three patients with COPD were included while in a stable state and followed up monthly until exacerbation or for a maximum of 6 months. The patients completed the Clinical COPD Questionnaire and Medical Research Council dyspnea scale questionnaires, and exhaled breath condensate was collected, followed by spirometry, impulse oscillometry, and sputum induction. Ten patients were chronically colonized (ie, colonized at all visits) with Haemophilus influenzae during stable phase. These patients had higher sputum levels of leukotriene B4 (Pchronically colonized patients. The difference in airway inflammation seen during stable phase in patients chronically colonized with H. influenzae was not observed during exacerbations. Some COPD patients who were chronically colonized with H. influenzae during stable phase showed increased airway inflammation and reduced lung volumes when compared with non-chronically colonized patients.

  10. Chronic Inflammation in Obesity and the Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Rosário Monteiro

    2010-01-01

    Full Text Available The increasing incidence of obesity and the metabolic syndrome is disturbing. The activation of inflammatory pathways, used normally as host defence, reminds the seriousness of this condition. There is probably more than one cause for activation of inflammation. Apparently, metabolic overload evokes stress reactions, such as oxidative, inflammatory, organelle and cell hypertrophy, generating vicious cycles. Adipocyte hypertrophy, through physical reasons, facilitates cell rupture, what will evoke an inflammatory reaction. Inability of adipose tissue development to engulf incoming fat leads to deposition in other organs, mainly in the liver, with consequences on insulin resistance. The oxidative stress which accompanies feeding, particularly when there is excessive ingestion of fat and/or other macronutrients without concomitant ingestion of antioxidant-rich foods/beverages, may contribute to inflammation attributed to obesity. Moreover, data on the interaction of microbiota with food and obesity brought new hypothesis for the obesity/fat diet relationship with inflammation. Beyond these, other phenomena, for instance psychological and/or circadian rhythm disturbances, may likewise contribute to oxidative/inflammatory status. The difficulty in the management of obesity/metabolic syndrome is linked to their multifactorial nature where environmental, genetic and psychosocial factors interact through complex networks.

  11. Chronic inflammation, immune response, and infection in abdominal aortic aneurysms

    DEFF Research Database (Denmark)

    Lindholt, Jes Sanddal; Shi, G-P

    2006-01-01

    Abdominal aortic aneurysms (AAA) are associated with atherosclerosis, transmural degenerative processes, neovascularization, decrease in content of vascular smooth muscle cells, and a chronic infiltration, mainly located in the outer aortic wall. The chronic infiltration consists mainly of macrop......Abdominal aortic aneurysms (AAA) are associated with atherosclerosis, transmural degenerative processes, neovascularization, decrease in content of vascular smooth muscle cells, and a chronic infiltration, mainly located in the outer aortic wall. The chronic infiltration consists mainly...... matrix metalloproteases and cysteine proteases for aortic matrix remodeling. The lymphocyte activation may be mediated by microorganisms as well as autoantigens generated from vascular structural proteins, perhaps through molecular mimicry. As in autoimmune diseases, the risk of AAA is increased...

  12. Chronic plus binge ethanol exposure causes more severe pancreatic injury and inflammation

    International Nuclear Information System (INIS)

    Ren, Zhenhua; Yang, Fanmuyi; Wang, Xin; Wang, Yongchao; Xu, Mei; Frank, Jacqueline A.; Ke, Zun-ji; Zhang, Zhuo; Shi, Xianglin; Luo, Jia

    2016-01-01

    Alcohol abuse increases the risk for pancreatitis. The pattern of alcohol drinking may impact its effect. We tested a hypothesis that chronic ethanol consumption in combination with binge exposure imposes more severe damage to the pancreas. C57BL/6 mice were divided into four groups: control, chronic ethanol exposure, binge ethanol exposure and chronic plus binge ethanol exposure. For the control group, mice were fed with a liquid diet for two weeks. For the chronic ethanol exposure group, mice were fed with a liquid diet containing 5% ethanol for two weeks. In the binge ethanol exposure group, mice were treated with ethanol by gavage (5 g/kg, 25% ethanol w/v) daily for 3 days. For the chronic plus binge exposure group, mice were fed with a liquid diet containing 5% ethanol for two weeks and exposed to ethanol by gavage during the last 3 days. Chronic and binge exposure alone caused minimal pancreatic injury. However, chronic plus binge ethanol exposure induced significant apoptotic cell death. Chronic plus binge ethanol exposure altered the levels of alpha-amylase, glucose and insulin. Chronic plus binge ethanol exposure caused pancreatic inflammation which was shown by the macrophages infiltration and the increase of cytokines and chemokines. Chronic plus binge ethanol exposure increased the expression of ADH1 and CYP2E1. It also induced endoplasmic reticulum stress which was demonstrated by the unfolded protein response. In addition, chronic plus binge ethanol exposure increased protein oxidation and lipid peroxidation, indicating oxidative stress. Therefore, chronic plus binge ethanol exposure is more detrimental to the pancreas. - Highlights: • Chronic plus binge alcohol drinking causes more pancreatic injury. • Chronic plus binge alcohol drinking induces more pancreatic inflammation. • Chronic plus binge alcohol causes more endoplasmic reticulum stress and oxidative stress.

  13. Adaptations in responsiveness of brainstem pain-modulating neurons in acute compared to chronic inflammation

    Science.gov (United States)

    Cleary, Daniel R.; Heinricher, Mary M.

    2013-01-01

    Despite similar behavioral hypersensitivity, acute and chronic pain have distinct neural bases. Here we used intraplantar injection of Complete Freund’s Adjuvant (CFA) to directly compare activity of pain-modulating neurons in the rostral ventromedial medulla (RVM) in acute versus chronic inflammation. Heat- and von Frey-evoked withdrawal reflexes and corresponding RVM neuronal activity were recorded in lightly anesthetized animals either during the first hour after CFA injection (acute) or 3–10 days later (chronic). Thermal and modest mechanical hyperalgesia during acute inflammation were associated with increases in the spontaneous activity of pain-facilitating ON-cells and suppression of pain-inhibiting OFF-cells. Acute hyperalgesia was reversed by RVM block, showing that the increased activity of RVM ON-cells is necessary for acute behavioral hypersensitivity. In chronic inflammation, thermal hyperalgesia had resolved, but mechanical hyperalgesia had become pronounced. The spontaneous discharges of ON- and OFF-cells were not different from controls, but the mechanical response thresholds for both cell classes were reduced into the innocuous range. RVM block in the chronic condition worsened mechanical hyperalgesia. These studies identify distinct contributions of RVM ON- and OFF-cells to acute and chronic inflammatory hyperalgesia. During early immune-mediated inflammation, ON-cell spontaneous activity promotes hyperalgesia. After inflammation is established, the anti-nociceptive influence of OFF-cells is dominant, yet the lowered threshold for the OFF-cell pause allows behavioral responses to stimuli that would normally be considered innocuous. The efficacy of OFF-cells in counteracting sensitization of ascending transmission pathways could therefore be an important determining factor in development of chronic inflammatory pain. PMID:23588008

  14. Adaptations in responsiveness of brainstem pain-modulating neurons in acute compared with chronic inflammation.

    Science.gov (United States)

    Cleary, Daniel R; Heinricher, Mary M

    2013-06-01

    Despite similar behavioral hypersensitivity, acute and chronic pain have distinct neural bases. We used intraplantar injection of complete Freund's adjuvant to directly compare activity of pain-modulating neurons in the rostral ventromedial medulla (RVM) in acute vs chronic inflammation. Heat-evoked and von Frey-evoked withdrawal reflexes and corresponding RVM neuronal activity were recorded in lightly anesthetized animals either during the first hour after complete Freund's adjuvant injection (acute) or 3 to 10 days later (chronic). Thermal and modest mechanical hyperalgesia during acute inflammation were associated with increases in the spontaneous activity of pain-facilitating ON-cells and suppression of pain-inhibiting OFF-cells. Acute hyperalgesia was reversed by RVM block, showing that the increased activity of RVM ON-cells is necessary for acute behavioral hypersensitivity. In chronic inflammation, thermal hyperalgesia had resolved but mechanical hyperalgesia had become pronounced. The spontaneous discharges of ON- and OFF-cells were not different from those in control subjects, but the mechanical response thresholds for both cell classes were reduced into the innocuous range. RVM block in the chronic condition worsened mechanical hyperalgesia. These studies identify distinct contributions of RVM ON- and OFF-cells to acute and chronic inflammatory hyperalgesia. During early immune-mediated inflammation, ON-cell spontaneous activity promotes hyperalgesia. After inflammation is established, the antinociceptive influence of OFF-cells is dominant, yet the lowered threshold for the OFF-cell pause allows behavioral responses to stimuli that would normally be considered innocuous. The efficacy of OFF-cells in counteracting sensitization of ascending transmission pathways could therefore be an important determining factor in development of chronic inflammatory pain. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All

  15. Liver stiffness measurement-based scoring system for significant inflammation related to chronic hepatitis B.

    Directory of Open Access Journals (Sweden)

    Mei-Zhu Hong

    Full Text Available Liver biopsy is indispensable because liver stiffness measurement alone cannot provide information on intrahepatic inflammation. However, the presence of fibrosis highly correlates with inflammation. We constructed a noninvasive model to determine significant inflammation in chronic hepatitis B patients by using liver stiffness measurement and serum markers.The training set included chronic hepatitis B patients (n = 327, and the validation set included 106 patients; liver biopsies were performed, liver histology was scored, and serum markers were investigated. All patients underwent liver stiffness measurement.An inflammation activity scoring system for significant inflammation was constructed. In the training set, the area under the curve, sensitivity, and specificity of the fibrosis-based activity score were 0.964, 91.9%, and 90.8% in the HBeAg(+ patients and 0.978, 85.0%, and 94.0% in the HBeAg(- patients, respectively. In the validation set, the area under the curve, sensitivity, and specificity of the fibrosis-based activity score were 0.971, 90.5%, and 92.5% in the HBeAg(+ patients and 0.977, 95.2%, and 95.8% in the HBeAg(- patients. The liver stiffness measurement-based activity score was comparable to that of the fibrosis-based activity score in both HBeAg(+ and HBeAg(- patients for recognizing significant inflammation (G ≥3.Significant inflammation can be accurately predicted by this novel method. The liver stiffness measurement-based scoring system can be used without the aid of computers and provides a noninvasive alternative for the prediction of chronic hepatitis B-related significant inflammation.

  16. Silica-induced Chronic Inflammation Promotes Lung Carcinogenesis in the Context of an Immunosuppressive Microenvironment

    Directory of Open Access Journals (Sweden)

    Javier Freire

    2013-08-01

    Full Text Available The association between inflammation and lung tumor development has been clearly demonstrated. However, little is known concerning the molecular events preceding the development of lung cancer. In this study, we characterize a chemically induced lung cancer mouse model in which lung cancer developed in the presence of silicotic chronic inflammation. Silica-induced lung inflammation increased the incidence and multiplicity of lung cancer in mice treated with N-nitrosodimethylamine, a carcinogen found in tobacco smoke. Histologic and molecular analysis revealed that concomitant chronic inflammation contributed to lung tumorigenesis through induction of preneoplastic changes in lung epithelial cells. In addition, silica-mediated inflammation generated an immunosuppressive microenvironment in which we observed increased expression of programmed cell death protein 1 (PD-1, transforming growth factor-β1, monocyte chemotactic protein 1 (MCP-1, lymphocyte-activation gene 3 (LAG3, and forkhead box P3 (FOXP3, as well as the presence of regulatory T cells. Finally, the K-RAS mutational profile of the tumors changed from Q61R to G12D mutations in the inflammatory milieu. In summary, we describe some of the early molecular changes associated to lung carcinogenesis in a chronic inflammatory microenvironment and provide novel information concerning the mechanisms underlying the formation and the fate of preneoplastic lesions in the silicotic lung.

  17. Vaccination promotes TH1-like inflammation and survival in chronic Pseudomonas aeruginosa pneumonia in rats

    DEFF Research Database (Denmark)

    Johansen, H K; Hougen, H P; Cryz, S J

    1995-01-01

    -polysaccharide toxin A conjugate, or sterile saline. After challenge none of the rats immunized with D-ALG toxin A died, in contrast to the other two vaccine groups combined (p = 0.03). A significant reduction in the severity of the macroscopic lung inflammation was seen in rats immunized with D-ALG toxin A, compared...... predominantly PMNs (TH2-like) to a chronic-type inflammation dominated by mononuclear leukocytes (TH1-like). In accordance, the antibody titers induced by the D-ALG toxin A vaccine were not different from those of the control rats after challenge. This study identifies a possible new way of modifying...... the inflammation and thereby preventing the PMN-mediated lung tissue damage during chronic P. aeruginosa lung infection in CF....

  18. Fatigue in chronic inflammation - a link to pain pathways.

    Science.gov (United States)

    Louati, Karine; Berenbaum, Francis

    2015-10-05

    Fatigue is a frequent symptom in several inflammatory diseases, particularly in rheumatic diseases. Elements of disease activity and cognitive and behavior aspects have been reported as causes of fatigue in patients with rheumatoid arthritis. Fatigue could be associated with activity of inflammatory rheumatism. Indeed, biologic agents targeting inflammatory cytokines are effective in fatigue. Fatigue is also associated with pain and depressive symptoms. Different pathways could be involved in fatigue and interact: the immune system with increased levels of pro-inflammatory cytokines (interleukin-1 and -6 and tumor necrosis factor alpha), dysregulation of the hypothalamic-pituitary-adrenal axis and neurological phenomena involving the central and autonomic nervous systems. A pro-inflammatory process could be involved in pain and behavioral symptoms. Inflammation could be a common link between fatigue, pain, and depression.

  19. Histidine-rich glycoprotein promotes macrophage activation and inflammation in chronic liver disease

    NARCIS (Netherlands)

    Bartneck, M.; Fech, V.; Ehling, J.; Govaere, O.; Warzecha, K.T.; Hittatiya, K.; Vucur, M.; Gautheron, J.; Luedde, T.; Trautwein, C.; Lammers, Twan Gerardus Gertudis Maria; Roskams, T.; Jahnen-Dechent, W.; Tacke, F.

    2016-01-01

    Pathogen- and injury-related danger signals as well as cytokines released by immune cells influence the functional differentiation of macrophages in chronic inflammation. Recently, the liver-derived plasma protein, histidine-rich glycoprotein (HRG), was demonstrated, in mouse tumor models, to

  20. Type I Interferon Modulates Monocyte Recruitment and Maturation in Chronic Inflammation

    NARCIS (Netherlands)

    Lee, P.Y.; Li, Y.; Kumagai, Y.; Xu, Y.; Weinstein, J.S.; Kellner, E.C.; Nacionales, D.G.; Butfiloski, E.J.; Rooijen, van N.; Akira, S; Sobel, E.S.; Satoh, M.; Reeves, W.H.

    2009-01-01

    Chronic inflammation is characterized by continuous recruitment and activation of immune cells such as monocytes in response to a persistent stimulus. Production of proinflammatory mediators by monocytes leads to tissue damage and perpetuates the inflammatory response. However, the mechanism(s)

  1. Toll-like receptors and chronic inflammation in rheumatic diseases: new developments

    NARCIS (Netherlands)

    Joosten, L.A.B.; Abdollahi-Roodsaz, S.; Dinarello, C.A.; O'Neill, L.; Netea, M.G.

    2016-01-01

    In the past few years, new developments have been reported on the role of Toll-like receptors (TLRs) in chronic inflammation in rheumatic diseases. The inhibitory function of TLR10 has been demonstrated. Receptors that enhance the function of TLRs, and several TLR inhibitors, have been identified.

  2. Green tea polyphenols attenuate deterioration of bone microarchitecture in female rats with systemic chronic inflammation

    Science.gov (United States)

    Introduction: Our previous study demonstrated that green tea polyphenols (GTP) benefit bone health in female rats with chronic inflammation, because of GTP’s antioxidant capacity. The current study further evaluates whether GTP can restore bone microstructure along with related mechanism in rats wit...

  3. Antioxidant Effect of Spirulina (Arthrospira) maxima on Chronic Inflammation Induced by Freund's Complete Adjuvant in Rats.

    Science.gov (United States)

    Gutiérrez-Rebolledo, Gabriel Alfonso; Galar-Martínez, Marcela; García-Rodríguez, Rosa Virginia; Chamorro-Cevallos, Germán A; Hernández-Reyes, Ana Gabriela; Martínez-Galero, Elizdath

    2015-08-01

    One of the major mechanisms in the pathogenesis of chronic inflammation is the excessive production of reactive oxygen and reactive nitrogen species, and therefore, oxidative stress. Spirulina (Arthrospira) maxima has marked antioxidant activity in vivo and in vitro, as well as anti-inflammatory activity in certain experimental models, the latter activity being mediated probably by the antioxidant activity of this cyanobacterium. In the present study, chronic inflammation was induced through injection of Freund's complete adjuvant (CFA) in rats treated daily with Spirulina (Arthrospira) maxima for 2 weeks beginning on day 14. Joint diameter, body temperature, and motor capacity were assessed each week. On days 0 and 28, total and differential leukocyte counts and serum oxidative damage were determined, the latter by assessing lipid peroxidation and protein carbonyl content. At the end of the study, oxidative damage to joints was likewise evaluated. Results show that S. maxima favors increased mobility, as well as body temperature regulation, and a number of circulating leukocytes, lymphocytes, and monocytes in specimens with CFA-induced chronic inflammation and also protects against oxidative damage in joint tissue as well as serum. In conclusion, the protection afforded by S. maxima against development of chronic inflammation is due to its antioxidant activity.

  4. High dietary fiber intake is associated with decreased inflammation and all-cause mortality in patients with chronic kidney disease

    OpenAIRE

    Raj Krishnamurthy, Vidya M.; Wei, Guo; Baird, Bradley C.; Murtaugh, Maureen; Chonchol, Michel B.; Raphael, Kalani L.; Greene, Tom; Beddhu, Srinivasan

    2011-01-01

    Chronic kidney disease is considered an inflammatory state and a high fiber intake is associated with decreased inflammation in the general population. Here, we determined whether fiber intake is associated with decreased inflammation and mortality in chronic kidney disease, and whether kidney disease modifies the associations of fiber intake with inflammation and mortality. To do this, we analyzed data from 14,543 participants in the National Health and Nutrition Examination Survey III. The ...

  5. Airway inflammation in severe chronic obstructive pulmonary disease

    International Nuclear Information System (INIS)

    Turato, Graziella; Zuin, Renzo; Miniati, Massimo

    2002-01-01

    Very few studies have been made in-patient with severe chronic obstructive pulmonary disease and some of them carried out, have demonstrated an increment in the intensity of the inflammatory answer in the space and these patients' alveolar walls. However, there are not enough studies on the inflammatory answer in the small airway and in the lung glasses, object of the present study, comparing it with patient with light (COPD) or without COPD, in spite of similar history of smoker

  6. Effect of chronic continual- and intermittent hypoxia-induced systemic inflammation on the cardiovascular system in rats.

    Science.gov (United States)

    Xu, Xiao-Mei; Yao, Dan; Cai, Xue-Ding; Ding, Cheng; Lin, Qian-Ding; Wang, Liang-Xing; Huang, Xiao-Ying

    2015-05-01

    Obstructive sleep apnea syndrome (OSAS) has been recognized as an important risk factor for cardiovascular morbidity and mortality. However, the underlying mechanisms are poorly understood. Present study aimed to investigate the role of NF-κB-dependent inflammation pathways in pathophysiological responses of cardiovascular system in OSAS. Thirty male specific pathogen-free (SPF) Sprague-Dawley rats were randomly assigned to normoxia (N) group, continual hypoxia (CH) group, and intermittent hypoxia (IH) group (n = 10) and were exposed to N (21% O2), CH (8% O2), or IH (6-11% O2 for 10 s and 21% O2 for 80 s in every 90 s) for 8 h/day for 35 days. The hemodynamic and pathomorphologic effects of IH and CH exposure were investigated as well as the expression of NF-κB-dependent inflammation factors. Chronic IH or CH significantly increased mean pulmonary arterial pressure (mPAP) in rats, while no significant changes occurred in mean carotid arterial pressure (mCAP). The ratio of right ventricle (RV) to left ventricle (LV) + septum (S) was significantly increased by both IH and CH, suggesting RV hypertrophy was induced by IH or CH. Elastic fiber staining showed an irregular pattern of elastic fiber distribution after hypoxia, and aortic tunica media thickness was increased. Both chronic IH and CH upregulated the expressions of transcription factor NF-κB and related pro-inflammatory cytokines and adhesion molecules. The current study expands our understanding that both IH and CH could activate the expression of NF-κB and related inflammatory factors as well as cause pathophysiologic damage to the cardiovascular system in OSAS. All these results provide further support to an emerging hypothesis that activation of NF-κB-dependent inflammation may play a central role in the pathophysiology of cardiovascular dysfunction in OSAS.

  7. Acute and chronic effects of smoking on inflammation markers in exhaled breath condensate in current smokers.

    Science.gov (United States)

    Koczulla, A-Rembert; Noeske, Sarah; Herr, Christian; Jörres, Rudolf A; Römmelt, Horst; Vogelmeier, Claus; Bals, Robert

    2010-01-01

    Long-term cigarette smoking is associated with pulmonary inflammation, but the acute effects of smoking have been less well studied. Analysis of the exhaled breath condensate (EBC) can provide noninvasive markers that might be indicative of inflammation. The aim of the study was to determine whether the pH , electrical conductivity and the levels of ammonium and interleukin 8 (IL-8) of EBC were altered in smokers and whether they changed after smoking a single cigarette. We included 19 healthy nonsmokers (controls), 29 asymptomatic smokers, 10 patients with stable chronic obstructive pulmonary disease (COPD) [Global Initiative for Chronic Obstructive Lung Disease stages (GOLD) stages II-III], and 10 patients with exacerbated COPD. In 13 smokers, EBC was also analyzed before and after smoking. EBC was obtained during 10 min tidal breathing with a cooled RTube. pH was determined after deaeration with argon. Acute smoking did not alter the pH or ammonium and IL-8 levels, but raised conductivity. As in COPD patients, the pH was significantly decreased in chronic smokers with a history of at least 10 pack-years compared to controls. EBC can be used to detect the acute and chronic effects of smoking. The increased conductivity of EBC after smoking suggests acute inflammatory effects. The reduced pH in chronic smokers shows cigarette-induced inflammation. 2009 S. Karger AG, Basel.

  8. Inflammation mediators in employees in chronic exposure to neurotoxicants

    Directory of Open Access Journals (Sweden)

    Galina Bodienkova

    2014-08-01

    Full Text Available Objectives: The aim of this work is to perform comparative estimation of cytokines levels in chlorinated hydrocarbons and metallic mercury exposure in employees in the dynamics of neurologic disorders formation. Material and Methods: The contents of cytokines IL-1β, IL-2, IL-4, IL-6, TNF-α, INF-γ were determined in blood sera using the method of hardphasic immunoferment analysis. The significance of different average values was assessed using the parametric and non-parametric criteria - Student (in normal distribution and Mann-Whitney tests taking into account the Bonferonni correction (non-difference from normal distribution. Results: It was shown that, a number of inflammation mediators with the dominance, depending on the expositional toxicant and expression of neurological deficiency, take part in the neurointoxication development. Healthy employees show pro-inflammatory responses with different expression degree, which dominate in the immune regulation processes regardless of the expositional factors (metallic mercury vapors and chlorinated hydrocarbons. Conclusions: The production intensity and interconnection between the pro- and anti-inflammatory cytokines may change in the occupational injuries of the nervous system development process. The decrease in the serum concentrations of cytokines along with the increase of clinical manifestation severity may prove dysregulation of the immune system, which promotes maintaining of pathological process and progradient process of neurointoxication. The most obvious is the imbalance of cytokines in the employees exposed to metallic mercury (in all the examined groups that increases neurointoxication in the distant period.

  9. Pro-calcitonin and inflammation in chronic hemodialysis

    Directory of Open Access Journals (Sweden)

    Hernán Trimarchi

    2013-10-01

    Full Text Available Procalcitonin (PCT has emerged as a marker of infection, a frequent complication in hemodialysis (HD. We analyzed PCT levels in chronic non-acutely infected HD subjects, assessed its correlation with inflammatory and nutritional markers and propose a PCT reference value for non-infected HD patients.In an observational cross-sectional study, 48 chronic HD patients and 36 controls were analyzed. Variables: age, gender, time on HD; diabetes; vascular access, PCT, C-reactive protein (CRP, albumin, malnutrition inflammatory score (MIS, hematocrit, leukocyte count, and body mass index (BMI. Subsequently, control (G1, n = 36, 43% vs. non-infected patients (G2, n = 48, 57% groups were compared. In control subjects (G1, age: 54.3 ± 13.7 years, range (r: 30-81; males: 19 (53%; median PCT 0.034 ng/ml (r: 0.02-0.08; median CRP 0.80 mg/dl (r: 0.36-3.9; p95 PCT level: 0.063 ng/ml. In G2, age: 60.2 ± 15.2 years; males 32 (67%, time on HD: 27.0 ± 24.4; diabetics: 19 (32%; median PCT: 0.26 ng/ml (r: 0.09-0.82; CRP: 1.1 mg/dl (r: 0.5-6.2; p95 PCT level: 0.8 ng/ml. In control subjects, PCT and CRP were significantly lower than in G2: PCT: 0.034 vs. 0.26 ng/ml, p = 0.0001; CRP: 0.8 vs. 1.1 mg/dl, p = 0.0004. PCT-CRP correlation in G2: ρ = 0.287, p = 0.048. PCT and CRP concentrations are elevated in chronic non-acutely infected HD subjects, independently of infection, diabetes and vascular access. A p95 PCT level of 0.8 ng/ml may be considered as the upper normal reference value in non-acutely infected HD subjects. The PCT cut-off level in HD is yet to be determined in HD.

  10. Occlusion of retinal capillaries caused by glial cell proliferation in chronic ocular inflammation.

    Science.gov (United States)

    Bianchi, E; Ripandelli, G; Feher, J; Plateroti, A M; Plateroti, R; Kovacs, I; Plateroti, P; Taurone, S; Artico, M

    2015-01-01

    The inner blood-retinal barrier is a gliovascular unit in which glial cells surround capillary endothelial cells and regulate retinal capillaries by paracrine interactions. During chronic ocular inflammation, microvascular complications can give rise to vascular proliferative lesions, which compromise visual acuity. This pathologic remodelling caused by proliferating Müller cells determines occlusion of retinal capillaries. The aim of the present study was to identify qualitative and quantitative alterations in the retinal capillaries in patients with post-traumatic chronic ocular inflammation or post-thrombotic vascular glaucoma. Moreover, we investigated the potential role of vascular endothelial growth factor (VEGF) and pro-inflammatory cytokines in retinal inflammation. Our electron microscopy findings demonstrated that during chronic ocular inflammation, thickening of the basement membrane, loss of pericytes and endothelial cells and proliferation of Müller cells occur with irreversible occlusion of retinal capillaries. Angiogenesis takes place as part of a regenerative reaction that results in fibrosis. We believe that VEGF and pro-inflammatory cytokines may be potential therapeutic targets in the treatment of this disease although further studies are required to confirm these findings.

  11. DNA damage induced by chronic inflammation contributes to colon carcinogenesis in mice.

    Science.gov (United States)

    Meira, Lisiane B; Bugni, James M; Green, Stephanie L; Lee, Chung-Wei; Pang, Bo; Borenshtein, Diana; Rickman, Barry H; Rogers, Arlin B; Moroski-Erkul, Catherine A; McFaline, Jose L; Schauer, David B; Dedon, Peter C; Fox, James G; Samson, Leona D

    2008-07-01

    Chronic inflammation increases cancer risk. While it is clear that cell signaling elicited by inflammatory cytokines promotes tumor development, the impact of DNA damage production resulting from inflammation-associated reactive oxygen and nitrogen species (RONS) on tumor development has not been directly tested. RONS induce DNA damage that can be recognized by alkyladenine DNA glycosylase (Aag) to initiate base excision repair. Using a mouse model of episodic inflammatory bowel disease by repeated administration of dextran sulfate sodium in the drinking water, we show that Aag-mediated DNA repair prevents colonic epithelial damage and reduces the severity of dextran sulfate sodium-induced colon tumorigenesis. Importantly, DNA base lesions expected to be induced by RONS and recognized by Aag accumulated to higher levels in Aag-deficient animals following stimulation of colonic inflammation. Finally, as a test of the generality of this effect we show that Aag-deficient animals display more severe gastric lesions that are precursors of gastric cancer after chronic infection with Helicobacter pylori. These data demonstrate that the repair of DNA lesions formed by RONS during chronic inflammation is important for protection against colon carcinogenesis.

  12. [Systemic inflammation among stable ex smokers with chronic obstructive pulmonary disease].

    Science.gov (United States)

    Morales S, Arturo; Dreyse D, Jorge; Díaz P, Orlando; Saldías P, Fernando; Carrasco, Marcela; Lisboa B, Carmen

    2010-08-01

    Low grade systemic inflammation is commonly observed in chronic obstructive pulmonary disease (COPD). To evaluate the extent of systemic inflammation in a group of ex-smokers with COPD in stable condition and its relation with pulmonary function and clinical manifestations. We studied 104 ex-smokers aged 69 ± 8 years (62 males) with mild to very severe COPD and 52 healthy non-smoker subjects aged 66 ± 11 years (13 males) as control group. High sensitivity serum C reactive protein (CRP), interleukin 6 (IL6), fibrinogen (F) and neutrophil count (Nc) were measured. Forced expiratory volume in the first minute (FEV1), inspiratory capacity (IC), arterial blood gases, six minutes walking test, dyspnea and body mass index (BMI) were measured, calculating the BODE index. Health status was assessed using the Saint George Respiratory Questionnaire (SGRQ), the chronic respiratory questionnaire (CRQ), registering the number of acute exacerbations (AE) during the previous year and inhaled steroids use. Systemic inflammation was considered present when levels of CRP or IL6 were above the percentile 95 of controls (7.98 mg/L and 3.42 pg/ml, respectively). COPD patients had significantly higher CRP and IL6 levels than controls. Their F and Nc levels were within normal limits. Systemic inflammation was present in 56 patients, which had similar disease severity and frequency of inhaled steroid use, compared with patients without inflammation. Patients with systemic inflammation had more AE in the previous year; lower inspiratory capacity, greater dyspnea during the six minutes walk test and worse SGRQ and CRQ scores. Low-grade systemic inflammation was found in 56 of 104 ex-smokers with COPD. This group showed a greater degree of lung hyperinflation, dyspnea on exercise and poor quality of life.

  13. Chronic gastrointestinal inflammation induces anxiety-like behavior and alters central nervous system biochemistry in mice.

    Science.gov (United States)

    Bercik, Premysl; Verdu, Elena F; Foster, Jane A; Macri, Joseph; Potter, Murray; Huang, Xiaxing; Malinowski, Paul; Jackson, Wendy; Blennerhassett, Patricia; Neufeld, Karen A; Lu, Jun; Khan, Waliul I; Corthesy-Theulaz, Irene; Cherbut, Christine; Bergonzelli, Gabriela E; Collins, Stephen M

    2010-12-01

    Clinical and preclinical studies have associated gastrointestinal inflammation and infection with altered behavior. We investigated whether chronic gut inflammation alters behavior and brain biochemistry and examined underlying mechanisms. AKR mice were infected with the noninvasive parasite Trichuris muris and given etanercept, budesonide, or specific probiotics. Subdiaphragmatic vagotomy was performed in a subgroup of mice before infection. Gastrointestinal inflammation was assessed by histology and quantification of myeloperoxidase activity. Serum proteins were measured by proteomic analysis, circulating cytokines were measured by fluorescence activated cell sorting array, and serum tryptophan and kynurenine were measured by liquid chromatography. Behavior was assessed using light/dark preference and step-down tests. In situ hybridization was used to assess brain-derived neurotrophic factor (BDNF) expression in the brain. T muris caused mild to moderate colonic inflammation and anxiety-like behavior that was associated with decreased hippocampal BDNF messenger RNA (mRNA). Circulating tumor necrosis factor-α and interferon-γ, as well as the kynurenine and kynurenine/tryptophan ratio, were increased. Proteomic analysis showed altered levels of several proteins related to inflammation and neural function. Administration of etanercept, and to a lesser degree of budesonide, normalized behavior, reduced cytokine and kynurenine levels, but did not influence BDNF expression. The probiotic Bifidobacterium longum normalized behavior and BDNF mRNA but did not affect cytokine or kynurenine levels. Anxiety-like behavior was present in infected mice after vagotomy. Chronic gastrointestinal inflammation induces anxiety-like behavior and alters central nervous system biochemistry, which can be normalized by inflammation-dependent and -independent mechanisms, neither of which requires the integrity of the vagus nerve. Copyright © 2010 AGA Institute. Published by Elsevier Inc

  14. Basal inflammation and innate immune response in chronic multisite musculoskeletal pain.

    Science.gov (United States)

    Generaal, Ellen; Vogelzangs, Nicole; Macfarlane, Gary J; Geenen, Rinie; Smit, Johannes H; Dekker, Joost; Penninx, Brenda W J H

    2014-08-01

    Dysregulation of the immune system may play a role in chronic pain, although study findings are inconsistent. This cross-sectional study examined whether basal inflammatory markers and the innate immune response are associated with the presence and severity of chronic multisite musculoskeletal pain. Data were used on 1632 subjects of the Netherlands Study of Depression and Anxiety. The Chronic Pain Grade questionnaire was used to determine the presence and severity of chronic multisite musculoskeletal pain. Subjects were categorized in a chronic multisite musculoskeletal pain group (n=754) and a control group (n=878). Blood levels of the basal inflammatory markers C-reactive protein, interleukin-6, and tumor necrosis factor-alpha were determined. To obtain a measure of the innate immune response, 13 inflammatory markers were assessed after lipopolysaccharide (LPS) stimulation in a subsample (n=707). Subjects with chronic multisite musculoskeletal pain showed elevated levels of basal inflammatory markers compared with controls, but statistical significance was lost after adjustment for lifestyle and disease variables. For some LPS-stimulated inflammatory markers, we did find elevated levels in subjects with chronic multisite musculoskeletal pain both before and after adjustment for covariates. Pain severity was not associated with inflammation within chronic pain subjects. An enhanced innate immune response in chronic multisite musculoskeletal pain may be examined as a potential biomarker for the onset or perpetuation of chronic pain. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  15. Role of oxidants/inflammation in declining renal function in chronic kidney disease and normal aging.

    Science.gov (United States)

    Vlassara, Helen; Torreggiani, Massimo; Post, James B; Zheng, Feng; Uribarri, Jaime; Striker, Gary E

    2009-12-01

    Oxidant stress (OS) and inflammation increase in normal aging and in chronic kidney disease (CKD), as observed in human and animal studies. In cross-sectional studies of the US population, these changes are associated with a decrease in renal function, which is exhibited by a significant proportion of the population. However, since many normal adults have intact renal function, and longitudinal studies show that some persons maintain normal renal function with age, the link between OS, inflammation, and renal decline is not clear. In aging mice, greater oxidant intake is associated with increased age-related CKD and mortality, which suggests that interventions that reduce OS and inflammation may be beneficial for older individuals. Both OS and inflammation can be readily lowered in normal subjects and patients with CKD stage 3-4 by a simple dietary modification that lowers intake and results in reduced serum and tissue levels of advanced glycation end products. Diabetic patients, including those with microalbuminuria, have a decreased ability to metabolize and excrete oxidants prior to observable changes in serum creatinine. Thus, OS and inflammation may occur in the diabetic kidney at an early time. We review the evidence that oxidants in the diet directly lead to increased serum levels of OS and inflammatory mediators in normal aging and in CKD. We also discuss a simple dietary intervention that helps reduce OS and inflammation, an important and achievable therapeutic goal for patients with CKD and aging individuals with reduced renal function.

  16. Metabolically induced liver inflammation leads to NASH and differs from LPS- or IL-1β-induced chronic inflammation.

    Science.gov (United States)

    Liang, Wen; Lindeman, Jan H; Menke, Aswin L; Koonen, Debby P; Morrison, Martine; Havekes, Louis M; van den Hoek, Anita M; Kleemann, Robert

    2014-05-01

    The nature of the chronic inflammatory component that drives the development of non-alcoholic steatohepatitis (NASH) is unclear and possible inflammatory triggers have not been investigated systematically. We examined the effect of non-metabolic triggers (lipopolysaccharide (LPS), interleukin-1β (IL-1β), administered by slow-release minipumps) and metabolic dietary triggers (carbohydrate, cholesterol) of inflammation on the progression of bland liver steatosis (BS) to NASH. Transgenic APOE3*Leiden.huCETP (APOE3L.CETP) mice fed a high-fat diet (HFD) developed BS after 10 weeks. Then, inflammatory triggers were superimposed or not (control) for six more weeks. Mouse livers were analyzed with particular emphasis on hallmarks of inflammation which were defined in human liver biopsies with and without NASH. Livers of HFD-treated control mice remained steatotic and did not progress to NASH. All four inflammatory triggers activated hepatic nuclear factor-κB (NF-κB) significantly and comparably (≥5-fold). However, HFD+LPS or HFD+IL-1β did not induce a NASH-like phenotype and caused intrahepatic accumulation of almost exclusively mononuclear cells. By contrast, mice treated with metabolic triggers developed NASH, characterized by enhanced steatosis, hepatocellular hypertrophy, and formation of mixed-type inflammatory foci containing myeloperoxidase-positive granulocytes (neutrophils) as well as mononuclear cells, essentially as observed in human NASH. Specific for the metabolic inducers was an activation of the proinflammatory transcription factor activator protein-1 (AP-1), neutrophil infiltration, and induction of risk factors associated with human NASH, that is, dyslipidemia (by cholesterol) and insulin resistance (by carbohydrate). In conclusion, HFD feeding followed by NF-κB activation per se (LPS, IL-1β) does not promote the transition from BS to NASH. HFD feeding followed by metabolically evoked inflammation induces additional inflammatory components

  17. Increased arterial inflammation in individuals with stage 3 chronic kidney disease

    Energy Technology Data Exchange (ETDEWEB)

    Takx, Richard A.P. [Massachusetts General Hospital and Harvard Medical School, Cardiac MR PET CT Program, Boston, MA (United States); University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); MacNabb, Megan H.; Emami, Hamed; Abdelbaky, Amr; Lavender, Zachary R. [Massachusetts General Hospital and Harvard Medical School, Cardiac MR PET CT Program, Boston, MA (United States); Singh, Parmanand [Massachusetts General Hospital and Harvard Medical School, Cardiac MR PET CT Program, Boston, MA (United States); New York Presbyterian Hospital, Weill Cornell Medical College, Division of Cardiology, New York, NY (United States); Di Carli, Marcelo; Taqueti, Viviany; Foster, Courtney [Brigham and Women' s Hospital and Harvard Medical School, Division of Radiology, Department of Medicine, Boston, MA (United States); Mann, Jessica; Comley, Robert A.; Weber, Chek Ing Kiu [F. Hoffmann-La Roche Ltd., Basel (Switzerland); Tawakol, Ahmed [Massachusetts General Hospital and Harvard Medical School, Cardiac MR PET CT Program, Boston, MA (United States); Massachusetts General Hospital and Harvard Medical School, Cardiology Division, Boston, MA (United States); Massachusetts General Hospital, Boston, MA (United States)

    2016-02-15

    While it is well known that patients with chronic kidney disease (CKD) are at increased risk for the development and progression of atherosclerosis, it is not known whether arterial inflammation is increased in mild CKD. The aim of this study was to compare arterial inflammation using {sup 18}F-FDG PET/CT in patients with CKD and in matched controls. This retrospective study included 128 patients undergoing FDG PET/CT imaging for clinical indications, comprising 64 patients with stage 3 CKD and 64 control patients matched by age, gender, and cancer history. CKD was defined according to guidelines using a calculated glomerular filtration rate (eGFR). Arterial inflammation was measured in the ascending aorta as FDG uptake on PET. Background FDG uptake (venous, subcutaneous fat and muscle) were recorded. Coronary artery calcification (CAC) was assessed using the CT images. The impact of CKD on arterial inflammation and CAC was then assessed. Arterial inflammation was higher in patients with CKD than in matched controls (standardized uptake value, SUV: 2.41 ± 0.49 vs. 2.16 ± 0.43; p = 0.002). Arterial SUV correlated inversely with eGFR (r = -0.299, p = 0.001). Venous SUV was also significantly elevated in patients with CKD, while subcutaneous fat and muscle tissue SUVs did not differ between groups. Moreover, arterial SUV remained significantly elevated in patients with CKD compared to controls after correcting for muscle and fat background, and also remained significant after adjusting for clinical risk factors. Further, CKD was associated with arterial inflammation (SUV) independent of the presence of subclinical atherosclerosis (CAC). Moderate CKD is associated with increased arterial inflammation beyond that of controls. Further, the increased arterial inflammation is independent of presence of subclinical atherosclerosis. Current risk stratification tools may underestimate the presence of atherosclerosis in patients with CKD and thereby the risk of

  18. Vaccination promotes TH1-like inflammation and survival in chronic Pseudomonas aeruginosa pneumonia. A new prophylactic principle

    DEFF Research Database (Denmark)

    Johansen, H K; Cryz, S J; Hougen, H P

    1997-01-01

    The ongoing lung tissue damage in chronically Pseudomonas aeruginosa infected cystic fibrosis (CF) patients has been shown to be caused by elastase liberated from polymorphonuclear leukocytes (PMN), which dominate the chronic inflammation in these patients. Most CF patients, however, contract...... the chronic lung infection with P. aeruginosa after a one-year period (median) of intermittent colonization. Therefore, prevention of the onset of the chronic infection or prevention of the dominance of the inflammation by PMNs would be important goals for a vaccine strategy against P. aeruginosa in CF...... of the vaccines could prevent chronic lung inflammation. After challenge, however, none of the rats immunized with D-ALG TA died in contrast to the other vaccine groups combined (p = 0.03). In addition, the inflammatory response changed from an acute type inflammation dominated by PMNs as in CF patients...

  19. ROLE OF SYSTEMATIC INFLAMMATION IN THE DEVELOPMENT OF COMORBIDITY IN CASE OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE

    Directory of Open Access Journals (Sweden)

    V. A. Nikitin

    2017-01-01

    Full Text Available Often local inflammation develops into systemic one with total inflammatory response of endotheliocytes, plasma and cellular blood factors, connective tissue, and at the final stages it is manifested through microcirculatory disorders in vital organs and tissues. At present two aspects are being investigated related to systemic inflammation in chronic obstructive pulmonary disease (COPD. Firstly, it is the evaluation of inflammatory load through testing the level of inflammation markers in blood. Secondly, now it is generally recognized that a number of typical extrapulmonary disorders and concurrent diseases develops in COPD patients. Regardless of these general pathogenic mechanisms, the one thing is clear: cardiovascular diseases, body weight loss, osteoporosis and a number of other extrapulmonary manifestations of COPD are related to systematic inflammatory response.

  20. Airway Inflammation in Chronic Rhinosinusitis with Nasal Polyps and Asthma: The United Airways Concept Further Supported

    DEFF Research Database (Denmark)

    Håkansson, Kåre; Bachert, Claus; Konge, Lars

    2015-01-01

    Background It has been established that patients with chronic rhinosinusitis with nasal polyps (CRSwNP) often have co-existing asthma. Objective We aimed to test two hypotheses: (i) upper and lower airway inflammation in CRSwNP is uniform in agreement with the united airways concept; and (ii......) bronchial inflammation exists in all CRSwNP patients irrespective of clinical asthma status. Methods We collected biopsies from nasal polyps, inferior turbinates and bronchi of 27 CRSwNP patients and 6 controls. All participants were evaluated for lower airway disease according to international guidelines...... cytokines measured, IL-13 was significantly increased in bronchial biopsies from CRSwNP patients with, but not without asthma. Conclusion Our findings support the united airways concept; however, we did not find evidence for subclinical bronchial inflammation in CRSwNP patients without asthma. Finally...

  1. Iron Status and Inflammation in Early Stages of Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Ewelina Łukaszyk

    2015-06-01

    Full Text Available Background/Aims: One of the most common causes of anemia of chronic disease (ACD is chronic kidney disease. The main pathomechanism responsible for ACD is subclinical inflammation. The key element involved in iron metabolism is hepcidin, however, studies on new indices of iron status are in progress.The aim of the study was to assess the iron status in patients in early stages of chronic kidney disease, iron correlation with inflammation parameters and novel biomarkers of iron metabolism. Methods: The study included 69 patients. Standard laboratory measurements were used to measure the iron status, complete blood count, fibrinogen, prothrombin index, C-reactive protein concentration (CRP, creatinine, urea, uric acid. Commercially available kits were used to measure high-sensitivity CRP, interleukin 6 (IL-6, hepcidin-25, hemojuvelin, soluble transferrin receptor (sTfR, growth differentiation factor-15 (GDF-15 and zonulin. Results: Absolute iron deficiency was present in 17% of the patients, functional iron deficiency was present in 12% of the patients. Functional iron deficiency was associated with significantly higher serum levels of fibrinogen, ferritin, transferrin saturation, total iron binding capacity, hepcidin and older age relative to patients with absolute iron deficiency. In comparison with patients without iron deficiency, patients with functional iron deficiency were older, with lower prothrombin index, higher fibrinogen, CRP, hsCRP, sTfR, GDF-15, urea and lower eGFR. Hepcidin was predicted by markers of inflammation:ferritin, fibrinogen and IL-6. Conclusion: Inflammation is correlated with iron status. Novel biomarkers of iron metabolism might be useful to distinguish iron deficiency anemia connected with inflammation and absolute iron deficiency.

  2. Implanted neural electrodes cause chronic, local inflammation that is correlated with local neurodegeneration

    Science.gov (United States)

    McConnell, George C.; Rees, Howard D.; Levey, Allan I.; Gutekunst, Claire-Anne; Gross, Robert E.; Bellamkonda, Ravi V.

    2009-10-01

    Prosthetic devices that are controlled by intracortical electrodes recording one's 'thoughts' are a reality today, and no longer merely in the realm of science fiction. However, widespread clinical use of implanted electrodes is hampered by a lack of reliability in chronic recordings, independent of the type of electrodes used. One major hypothesis has been that astroglial scar electrically impedes the electrodes. However, there is a temporal discrepancy between stabilization of scar's electrical properties and recording failure with recording failure lagging by 1 month. In this study, we test a possible explanation for this discrepancy: the hypothesis that chronic inflammation, due to the persistent presence of the electrode, causes a local neurodegenerative state in the immediate vicinity of the electrode. Through modulation of chronic inflammation via stab wound, electrode geometry and age-matched control, we found that after 16 weeks, animals with an increased level of chronic inflammation were associated with increased neuronal and dendritic, but not axonal, loss. We observed increased neuronal and dendritic loss 16 weeks after implantation compared to 8 weeks after implantation, suggesting that the local neurodegenerative state is progressive. After 16 weeks, we observed axonal pathology in the form of hyperphosphorylation of the protein tau in the immediate vicinity of the microelectrodes (as observed in Alzheimer's disease and other tauopathies). The results of this study suggest that a local, late onset neurodegenerative disease-like state surrounds the chronic electrodes and is a potential cause for chronic recording failure. These results also inform strategies to enhance our capability to attain reliable long-term recordings from implantable electrodes in the CNS.

  3. Eosinophilic airway inflammation: role in asthma and chronic obstructive pulmonary disease

    Science.gov (United States)

    George, Leena; Brightling, Christopher E.

    2016-01-01

    The chronic lung diseases, asthma and chronic obstructive pulmonary disease (COPD), are common affecting over 500 million people worldwide and causing substantial morbidity and mortality. Asthma is typically associated with Th2-mediated eosinophilic airway inflammation, in contrast to neutrophilic inflammation observed commonly in COPD. However, there is increasing evidence that the eosinophil might play an important role in 10–40% of patients with COPD. Consistently in both asthma and COPD a sputum eosinophilia is associated with a good response to corticosteroid therapy and tailored strategies aimed to normalize sputum eosinophils reduce exacerbation frequency and severity. Advances in our understanding of the multistep paradigm of eosinophil recruitment to the airway, and the consequence of eosinophilic inflammation, has led to the development of new therapies to target these molecular pathways. In this article we discuss the mechanisms of eosinophilic trafficking, the tools to assess eosinophilic airway inflammation in asthma and COPD during stable disease and exacerbations and review current and novel anti-eosinophilic treatments. PMID:26770668

  4. Is Chronic Inflammation a Possible Cause of Obesity-Related Depression?

    OpenAIRE

    Magdalena Olszanecka-Glinianowicz; Barbara Zahorska-Markiewicz; Piotr Kocełak; Joanna Janowska; Elżbieta Semik-Grabarczyk; Tomasz Wikarek; Wojciech Gruszka; Piotr Dąbrowski

    2009-01-01

    Adult obesity has been associated with depression, especially in women. Whether depression leads to obesity or obesity causes depression is unclear. Chronic inflammation is observed in obesity and depression. In 63 obese women without additional diseases depression level was assessed with the Beck's questionnaire. After evaluation of depression level study group was divided into groups according to the mood status (A—without depression, B—mild depression, and C—severe depression), and serum c...

  5. Duration of chronic inflammation alters gene expression in muscle from untreated girls with juvenile dermatomyositis

    Directory of Open Access Journals (Sweden)

    Gordish-Dressman Heather

    2008-07-01

    Full Text Available Abstract Background To evaluate the impact of the duration of chronic inflammation on gene expression in skeletal muscle biopsies (MBx from untreated children with juvenile dermatomyositis (JDM and identify genes and biological processes associated with the disease progression, expression profiling data from 16 girls with active symptoms of JDM greater than or equal to 2 months were compared with 3 girls with active symptoms less than 2 months. Results Seventy-nine genes were differentially expressed between the groups with long or short duration of untreated disease. Genes involved in immune responses and vasculature remodelling were expressed at a higher level in muscle biopsies from children with greater or equal to 2 months of symptoms, while genes involved in stress responses and protein turnover were expressed at a lower level. Among the 79 genes, expression of 9 genes showed a significant linear regression relationship with the duration of untreated disease. Five differentially expressed genes – HLA-DQA1, smooth muscle myosin heavy chain, clusterin, plexin D1 and tenomodulin – were verified by quantitative RT-PCR. The chronic inflammation of longer disease duration was also associated with increased DC-LAMP+ and BDCA2+ mature dendritic cells, identified by immunohistochemistry. Conclusion We conclude that chronic inflammation alters the gene expression patterns in muscle of untreated children with JDM. Symptoms lasting greater or equal to 2 months were associated with dendritic cell maturation and anti-angiogenic vascular remodelling, directly contributing to disease pathophysiology.

  6. Cerebellar white matter inflammation and demyelination in chronic relapsing experimental allergic encephalomyelitis

    DEFF Research Database (Denmark)

    Wanscher, B.; Sørensen, P. S.; Juhler, M.

    1993-01-01

    Experimental allergic encephalomyelitis, demyelination, inflammation, immunology, neuropathology......Experimental allergic encephalomyelitis, demyelination, inflammation, immunology, neuropathology...

  7. Signs of ongoing inflammation in female patients with chronic widespread pain

    Science.gov (United States)

    Gerdle, Björn; Ghafouri, Bijar; Ghafouri, Nazdar; Bäckryd, Emmanuel; Gordh, Torsten

    2017-01-01

    Abstract This cross-sectional study investigates the plasma inflammatory profile of chronic widespread pain (CWP) patients compared to healthy controls (CON). Rather than analyzing a relatively few substances at a time, we used a new multiplex proximity extension assay (PEA) panel that enabled the simultaneous analysis of 92 inflammation-related proteins, mainly cytokines and chemokines. Seventeen women with CWP and 21 female CON participated and a venous blood sample was drawn from all subjects. Pain intensity and pain thresholds for pressure, heat, and cold were registered. A PEA panel (92 proteins) was used to analyze the blood samples. Multivariate data analysis by projection was used in the statistical analyses. Eleven proteins significantly differentiated the CON and CWP subjects (R2 = 0.58, Q2 = 0.37, analysis of variance of cross-validated predictive residuals P = 0.006). It was not possible to significantly regress pain thresholds within each group (CON or CWP). Positive significant correlations existed between several proteins and pain intensities in CWP, but the model reliability of the regression was poor. CWP was associated with systemic low-grade inflammation. Larger studies are needed to confirm the results and to investigate which alterations are condition-specific and which are common across chronic pain conditions. The presence of inflammation could promote the spreading of pain, a hallmark sign of CWP. As it has been suggested that prevalent comorbidities to pain (e.g., depression and anxiety, poor sleep, and tiredness) also are associated with inflammation, it will be important to determine whether inflammation may be a common mediator. PMID:28248866

  8. Chronic Mild Prenatal Stress Exacerbates the Allergen-Induced Airway Inflammation in Rats

    Directory of Open Access Journals (Sweden)

    Paulo J. Nogueira

    1999-01-01

    Full Text Available The effects of chronic mild prenatal stress on leukocyte infiltration into the airways was investigated in rat offspring. The chronic prenatal stress consisted of transitory and variable changes in the rat's living conditions. Offspring at adult age were actively sensitized (day 0 and intratracheally challenged (day 14 with ovalbumin. Bronchoalveolar lavage was performed in the offspring at 48 h after intratracheal challenge with ovalbumin. A significant increase in total leukocyte infiltration was observed in the nonstressed offspring group and this was associated with a marked recruitment of eosinophils without a significant effect on the influx of neutrophils and mononuclear cells. In the prenatal stressed offspring, the counts of both total leukocyte and eosinophils, as well as mononuclear cells, was increased by 50% compared to the non-stressed offspring. We provide here the first experimental evidence that chronic mild unpredictable prenatal stress produces a marked increase in the allergen-induced airway inflammation in the rat offspring.

  9. Methylprednisolone stiffens aortas in lipopolysaccharide-induced chronic inflammation in rats.

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    Ya-Hui Ko

    Full Text Available INTRODUCTION: Glucocorticoids are commonly used as therapeutic agents in many acute and chronic inflammatory and auto-immune diseases. The current study investigated the effects of methylprednisolone (a synthetic glucocorticoid on aortic distensibility and vascular resistance in lipopolysaccharide-induced chronic inflammation in male Wistar rats. METHODS: Chronic inflammation was induced by implanting a subcutaneous slow-release ALZET osmotic pump (1 mg kg(-1 day(-1 lipopolysaccharide for either 2 or 4 weeks. Arterial wave transit time (τ was derived to describe the elastic properties of aortas using the impulse response function of the filtered aortic input impedance spectra. RESULTS: Long-term lipopolysaccharide challenge enhanced the expression of advanced glycation end products (AGEs in the aortas. Lipopolysaccharide also upregulated the inducible form of nitric oxide synthase to produce high levels of nitric oxide (NO, which resulted in vasodilation, as evidenced by the fall in total peripheral resistance (Rp . However, lipopolysaccharide challenge did not influence the elastic properties of aortas, as shown by the unaltered τ. The NO-mediated vascular relaxation may counterbalance the AGEs-induced arterial stiffening so that the aortic distensibility remained unaltered. Treating lipopolysaccharide-challenged rats with methylprednisolone prevented peripheral vasodilation because of its ability to increase Rp . However, methylprednisolone produced an increase in aorta stiffness, as manifested by the significant decline in τ. The diminished aortic distensibility by methylprednisolone paralleled a significant reduction in NO plasma levels, in the absence of any significant changes in AGEs content. CONCLUSION: Methylprednisolone stiffens aortas and elastic arteries in lipopolysaccharide-induced chronic inflammation in rats, for NO activity may be dominant as a counteraction of AGEs.

  10. Guidance Cue Netrin-1 and the Regulation of Inflammation in Acute and Chronic Kidney Disease

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    Punithavathi Ranganathan

    2014-01-01

    Full Text Available Acute kidney injury (AKI is a common problem in the hospital setting and intensive care unit. Despite improved understanding, there are no effective therapies available to treat AKI. A large body of evidence strongly suggests that ischemia reperfusion injury is an inflammatory disease mediated by both adaptive and innate immune systems. Cell migration also plays an important role in embryonic development and inflammation, and this process is highly regulated to ensure tissue homeostasis. One such paradigm exists in the developing nervous system, where neuronal migration is mediated by a balance between chemoattractive and chemorepulsive signals. The ability of the guidance molecule netrin-1 to repulse or abolish attraction of neuronal cells expressing the UNC5B receptor makes it an attractive candidate for the regulation of inflammatory cell migration. Recent identification of netrin-1 as regulators of immune cell migration has led to a large number of studies looking into how netrin-1 controls inflammation and inflammatory cell migration. This review will focus on recent advances in understanding netrin-1 mediated regulation of inflammation during acute and chronic kidney disease and whether netrin-1 and its receptor activation can be used to treat acute and chronic kidney disease.

  11. A20 prevents chronic liver inflammation and cancer by protecting hepatocytes from death

    Science.gov (United States)

    Catrysse, L; Farhang Ghahremani, M; Vereecke, L; Youssef, S A; Mc Guire, C; Sze, M; Weber, A; Heikenwalder, M; de Bruin, A; Beyaert, R; van Loo, G

    2016-01-01

    An important regulator of inflammatory signalling is the ubiquitin-editing protein A20 that acts as a break on nuclear factor-κB (NF-κB) activation, but also exerts important cytoprotective functions. A20 knockout mice are cachectic and die prematurely due to excessive multi-organ inflammation. To establish the importance of A20 in liver homeostasis and pathology, we developed a novel mouse line lacking A20 specifically in liver parenchymal cells. These mice spontaneously develop chronic liver inflammation but no fibrosis or hepatocellular carcinomas, illustrating an important role for A20 in normal liver tissue homeostasis. Hepatocyte-specific A20 knockout mice show sustained NF-κB-dependent gene expression in the liver upon tumor necrosis factor (TNF) or lipopolysaccharide injection, as well as hepatocyte apoptosis and lethality upon challenge with sublethal doses of TNF, demonstrating an essential role for A20 in the protection of mice against acute liver failure. Finally, chronic liver inflammation and enhanced hepatocyte apoptosis in hepatocyte-specific A20 knockout mice was associated with increased susceptibility to chemically or high fat-diet-induced hepatocellular carcinoma development. Together, these studies establish A20 as a crucial hepatoprotective factor. PMID:27253414

  12. Gut-associated lymphoid tissue, T cell trafficking, and chronic intestinal inflammation.

    Science.gov (United States)

    Koboziev, Iurii; Karlsson, Fridrik; Grisham, Matthew B

    2010-10-01

    The etiologies of the inflammatory bowel diseases (IBD; Crohn's disease, ulcerative colitis) have not been fully elucidated. However, there is very good evidence implicating T cell and T cell trafficking to the gut and its associated lymphoid tissue as important components in disease pathogenesis. The objective of this review is to provide an overview of the mechanisms involved in naive and effector T cell trafficking to the gut-associated lymphoid tissue (GALT; Peyer's patches, isolated lymphoid follicles), mesenteric lymph nodes and intestine in response to commensal enteric antigens under physiological conditions as well as during the induction of chronic gut inflammation. In addition, recent data suggests that the GALT may not be required for enteric antigen-driven intestinal inflammation in certain mouse models of IBD. These new data suggest a possible paradigm shift in our understanding of how and where naive T cells become activated to yield disease-producing effector cells. © 2010 New York Academy of Sciences.

  13. Roles of Chronic Low-Grade Inflammation in the Development of Ectopic Fat Deposition

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    Lulu Liu

    2014-01-01

    Full Text Available Pattern of fat distribution is a major determinant for metabolic homeostasis. As a depot of energy, the storage of triglycerides in adipose tissue contributes to the normal fat distribution. Decreased capacity of fat storage in adipose tissue may result in ectopic fat deposition in nonadipose tissues such as liver, pancreas, and kidney. As a critical biomarker of metabolic complications, chronic low-grade inflammation may have the ability to affect the process of lipid accumulation and further lead to the disorder of fat distribution. In this review, we have collected the evidence linking inflammation with ectopic fat deposition to get a better understanding of the underlying mechanism, which may provide us with novel therapeutic strategies for metabolic disorders.

  14. Noninvasive scoring system for significant inflammation related to chronic hepatitis B

    Science.gov (United States)

    Hong, Mei-Zhu; Ye, Linglong; Jin, Li-Xin; Ren, Yan-Dan; Yu, Xiao-Fang; Liu, Xiao-Bin; Zhang, Ru-Mian; Fang, Kuangnan; Pan, Jin-Shui

    2017-03-01

    Although a liver stiffness measurement-based model can precisely predict significant intrahepatic inflammation, transient elastography is not commonly available in a primary care center. Additionally, high body mass index and bilirubinemia have notable effects on the accuracy of transient elastography. The present study aimed to create a noninvasive scoring system for the prediction of intrahepatic inflammatory activity related to chronic hepatitis B, without the aid of transient elastography. A total of 396 patients with chronic hepatitis B were enrolled in the present study. Liver biopsies were performed, liver histology was scored using the Scheuer scoring system, and serum markers and liver function were investigated. Inflammatory activity scoring models were constructed for both hepatitis B envelope antigen (+) and hepatitis B envelope antigen (-) patients. The sensitivity, specificity, positive predictive value, negative predictive value, and area under the curve were 86.00%, 84.80%, 62.32%, 95.39%, and 0.9219, respectively, in the hepatitis B envelope antigen (+) group and 91.89%, 89.86%, 70.83%, 97.64%, and 0.9691, respectively, in the hepatitis B envelope antigen (-) group. Significant inflammation related to chronic hepatitis B can be predicted with satisfactory accuracy by using our logistic regression-based scoring system.

  15. Chronic obstructive pulmonary disease and obstructive sleep apnea: overlaps in pathophysiology, systemic inflammation, and cardiovascular disease.

    LENUS (Irish Health Repository)

    McNicholas, Walter T

    2012-02-01

    Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea syndrome represent two of the most prevalent chronic respiratory disorders in clinical practice, and cardiovascular diseases represent a major comorbidity in each disorder. The two disorders coexist (overlap syndrome) in approximately 1% of adults but asymptomatic lower airway obstruction together with sleep-disordered breathing is more prevalent. Although obstructive sleep apnea syndrome has similar prevalence in COPD as the general population, and vice versa, factors such as body mass index and smoking influence relationships. Nocturnal oxygen desaturation develops in COPD, independent of apnea\\/hypopnea, and is more severe in the overlap syndrome, thus predisposing to pulmonary hypertension. Furthermore, upper airway flow limitation contributes to nocturnal desaturation in COPD without apnea\\/hypopnea. Evidence of systemic inflammation in COPD and sleep apnea, involving C-reactive protein and IL-6, in addition to nuclear factor-kappaB-dependent pathways involving tumor necrosis factor-alpha and IL-8, provides insight into potential basic interactions between both disorders. Furthermore, oxidative stress develops in each disorder, in addition to activation and\\/or dysfunction of circulating leukocytes. These findings are clinically relevant because systemic inflammation may contribute to the pathogenesis of cardiovascular diseases and the cell\\/molecular pathways involved are similar to those identified in COPD and sleep apnea. However, the pathophysiological and clinical significance of systemic inflammation in COPD and sleep apnea is not proven, and thus, studies of patients with the overlap syndrome should provide insight into the mechanisms of systemic inflammation in COPD and sleep apnea, in addition to potential relationships with cardiovascular disease.

  16. Exercise alleviates depression related systemic inflammation in chronic obstructive pulmonary disease patients.

    Science.gov (United States)

    Abd El-Kader, Shehab M; Al-Jiffri, Osama H

    2016-12-01

    Depression is a highly prevalent co-morbidity in Chronic Obstructive Pulmonary Disease (COPD) which was shown to be associated with a worse course of disease, including reduced quality of life and increased symptoms burden, healthcare use, and even mortality. It has been speculated that systemic inflammation may play a role in the presence of depression. Currently, physical activity is an important lifestyle factor that has the potential to modify inflammatory cytokines and depression, however our understanding of how to use exercise effectively in COPD patients to alleviate depression related systemic inflammation is incomplete and has prompted our interest to identify the type and intensities of effective exercise. The aim of this study was to measure the changes in depression related systemic inflammation of aerobic exercise training in COPD patients in Jeddah area. Eighty patients with moderate severity of COPD participated in this study and were divided into two groups; the first group received aerobic exercise, whereas the second group received no exercise training for 12 weeks. The mean values of tumor necrosis factor-alpha (TNF-α), interleukin-4 (IL-4), interleukin-6 (IL-6), C-reactive protein (CRP) and Beck Depression Inventory (BDI) scores were significantly decreased in in group (A) after treatments, but the changes in group (B) were not significant .Also, there were significant differences between mean levels of the investigated parameters in group (A) and group (B) at the end of the study. Aerobic exercise is an effective treatment policy to improve depression related to systemic inflammation in patients with chronic obstructive pulmonary disease.

  17. Positive relationship between p42.3 gene and inflammation in chronic non-atrophic gastritis.

    Science.gov (United States)

    Chen, Ping; Cui, Yun; Fu, Qing Yan; Lu, You Yong; Fang, Jing Yuan; Chen, Xiao Yu

    2015-10-01

    Gastric cancer (GC) is a typical type of inflammation-related tumor. The p42.3 gene is shown to be highly expressed in GC, but its association with gastritis remains unknown. We aimed to explore the relationship between gastric inflammation and p42.3 gene in vitro and in vivo. Normal gastric epithelial cells (GES-1) were treated with Helicobacter pylori (H. pylori) and tumor necrosis factor (TNF)-α. Total cell mRNA and protein were extracted and collected, and polymerase chain reaction and Western blot were performed to determine the relative expression of p42.3 gene. In total, 291 biopsy samples from patients with chronic non-atrophic gastritis were collected and immunohistochemistry was used to measure the p42.3 protein expression. The association between p42.3 protein expression and the clinicopathological characteristics of these patients were analyzed. Both H. pylori and TNF-α significantly enhanced the p42.3 protein expression in GES-1 cells in a time and dose-dependent manner. In addition, p42.3 gene expression was positively associated with the severity of gastric mucosal inflammation and H. pylori infection (P = 0.000). Its expression was significantly more common in severe gastric inflammation and in H. pylori-infected cases. p42.3 gene expression is associated with gastric mucosal inflammation that can be upregulated by TNF-α and H. pylori infection. © 2015 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

  18. Leukocyte telomere length in major depression: correlations with chronicity, inflammation and oxidative stress--preliminary findings.

    Directory of Open Access Journals (Sweden)

    Owen M Wolkowitz

    2011-03-01

    Full Text Available Depression is associated with an unusually high rate of aging-related illnesses and early mortality. One aspect of "accelerated aging" in depression may be shortened leukocyte telomeres. When telomeres critically shorten, as often occurs with repeated mitoses or in response to oxidation and inflammation, cells may die. Indeed, leukocyte telomere shortening predicts early mortality and medical illnesses in non-depressed populations. We sought to determine if leukocyte telomeres are shortened in Major Depressive Disorder (MDD, whether this is a function of lifetime depression exposure and whether this is related to putative mediators, oxidation and inflammation.Leukocyte telomere length was compared between 18 unmedicated MDD subjects and 17 controls and was correlated with lifetime depression chronicity and peripheral markers of oxidation (F2-isoprostane/Vitamin C ratio and inflammation (IL-6. Analyses were controlled for age and sex.The depressed group, as a whole, did not differ from the controls in telomere length. However, telomere length was significantly inversely correlated with lifetime depression exposure, even after controlling for age (p<0.05. Average telomere length in the depressed subjects who were above the median of lifetime depression exposure (≥9.2 years' cumulative duration was 281 base pairs shorter than that in controls (p<0.05, corresponding to approximately seven years of "accelerated cell aging." Telomere length was inversely correlated with oxidative stress in the depressed subjects (p<0.01 and in the controls (p<0.05 and with inflammation in the depressed subjects (p<0.05.These preliminary data indicate that accelerated aging at the level of leukocyte telomeres is proportional to lifetime exposure to MDD. This might be related to cumulative exposure to oxidative stress and inflammation in MDD. This suggest that telomere shortening does not antedate depression and is not an intrinsic feature. Rather, telomere shortening

  19. Obesity, depression, and chronic low-grade inflammation in women with polycystic ovary syndrome.

    Science.gov (United States)

    Benson, S; Janssen, O E; Hahn, S; Tan, S; Dietz, T; Mann, K; Pleger, K; Schedlowski, M; Arck, P C; Elsenbruch, S

    2008-02-01

    Women with polycystic ovary syndrome (PCOS) present with multiple risk factors for cardiovascular diseases at a young age, including obesity and chronic low-grade inflammation. Since depression is common in PCOS, this study aimed to address whether depression correlates with indices of chronic low-grade inflammation beyond the association with obesity. Serum concentrations of IL-6, the stimulated production of IFN-gamma, TNF-alpha, IL-2, IL-4, IL-5, and IL-10, leukocyte numbers, and hsCRP were analyzed in 57 PCOS patients and 28 healthy women, together with clinical parameters, including body mass index (BMI), testosterone, and insulin resistance (HOMA-IR), and psychological parameters, including Beck Depression Inventory (BDI) and health-related quality-of-life (SF-36) scores. PCOS patients demonstrated significantly increased hsCRP, IL-6, and leukocyte numbers. Group differences in IL-6 and leukocyte numbers, but not hsCRP, disappeared after controlling for BMI. The stimulated production of IFN-gamma, TNF-alpha, IL-2, IL-4, and IL-5 was significantly decreased, irrespective of BMI. In PCOS, hsCRP, IL-6, and leukocyte numbers were correlated with BMI, HDL, diastolic blood pressure, and with insulin resistance. On the other hand, no correlations were found with depression scores or with PCOS-specific endocrine abnormalities. In regression models, BMI was a significant predictor of the key immune markers, and explained a large amount of variance, whereas BDI was not included in either model. These data confirm that obesity plays a pivotal role in inflammatory processes relevant to cardiovascular risk in women with PCOS. However, even lean PCOS patients may display subtle alterations in specific aspects of immunity. Our findings did not support a correlation of depression with chronic low-grade inflammation in PCOS.

  20. Inhalation of progesterone inhibits chronic airway inflammation of mice exposed to ozone.

    Science.gov (United States)

    Fei, Xia; Bao, Wuping; Zhang, Pengyu; Zhang, Xue; Zhang, Guoqing; Zhang, Yingying; Zhou, Xin; Zhang, Min

    2017-05-01

    Chronic ozone exposure leads to a model of mice with lung inflammation, emphysema and oxidative stress. Progesterone plays an important role in attenuating the neuroinflammation. We assume that progesterone will reduce the chronic airway inflammation exposed to ozone and evaluate whether combination of progesterone with glucocorticoids results in synergistic effects. C57/BL6 mice were exposed to ozone (2.5ppm, 3h) 12 times over 6 weeks, and were administered with progesterone (0.03 or 0.3mg/L; inhaled) alone or combined with budesonide (BUD) (0.2g/L) after each exposure until the tenth week. Mice were studied 24h after final exposure, cells and inflammatory mediators were assessed in bronchoalveolar lavage fluid (BALF) and lungs used for evaluation of glucocorticoids receptors (GR), p38 mitogen-activated protein kinase (MAPK) phosphorylation and nuclear transcription factor κB (NF-κB) activation. Exposure to ozone resulted in a marked lung neutrophilia. Moreover, in ozone-exposed group, the levels of oxidative stress-related interleukin (IL)-1β, IL-6, IL-8, IL-17A, activated NF-κB and p38MAPK, airway inflammatory cells infiltration density, mean linear intercept (Lm) were greatly increased, FEV 25 and glucocorticoids receptors (GR) were markedly decreased. Comparable to BUD, progesterone treatment dose-dependently led to a significant reduction of IL-1β, IL-6, IL-8, IL-17A, activated NF-κB and p38MAPK, and an increase of FEV 25 and GR. Progesterone combined with BUD resulted in dramatic changes, compared to monotherapy of BUD or progesterone. Therefore, these results demonstrate that chronic ozone exposure has profound airway inflammatory effects counteracted by progesterone and progesterone acts synergistically with glucocorticoids in attenuating the airway inflammation dose-dependently. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Adipose tissue deficiency and chronic inflammation in diabetic Goto-Kakizaki rats.

    Directory of Open Access Journals (Sweden)

    Bai Xue

    2011-02-01

    Full Text Available Type 2 diabetes (T2DM is a heterogeneous group of diseases that is progressive and involves multiple tissues. Goto-Kakizaki (GK rats are a polygenic model with elevated blood glucose, peripheral insulin resistance, a non-obese phenotype, and exhibit many degenerative changes observed in human T2DM. As part of a systems analysis of disease progression in this animal model, this study characterized the contribution of adipose tissue to pathophysiology of the disease. We sacrificed subgroups of GK rats and appropriate controls at 4, 8, 12, 16 and 20 weeks of age and carried out a gene array analysis of white adipose tissue. We expanded our physiological analysis of the animals that accompanied our initial gene array study on the livers from these animals. The expanded analysis included adipose tissue weights, HbA1c, additional hormonal profiles, lipid profiles, differential blood cell counts, and food consumption. HbA1c progressively increased in the GK animals. Altered corticosterone, leptin, and adiponectin profiles were also documented in GK animals. Gene array analysis identified 412 genes that were differentially expressed in adipose tissue of GKs relative to controls. The GK animals exhibited an age-specific failure to accumulate body fat despite their relatively higher calorie consumption which was well supported by the altered expression of genes involved in adipogenesis and lipogenesis in the white adipose tissue of these animals, including Fasn, Acly, Kklf9, and Stat3. Systemic inflammation was reflected by chronically elevated white blood cell counts. Furthermore, chronic inflammation in adipose tissue was evident from the differential expression of genes involved in inflammatory responses and activation of natural immunity, including two interferon regulated genes, Ifit and Iipg, as well as MHC class II genes. This study demonstrates an age specific failure to accumulate adipose tissue in the GK rat and the presence of chronic

  2. Therapeutic effect of aegiceras corniculatum in chronic granulomatous inflammation and arthritis

    International Nuclear Information System (INIS)

    Roome, T.; Razzak, A.; Ali, P.; Aziz, S.

    2014-01-01

    Chronic inflammation is a result of long lasting of acute inflammation, if not treated or resolved, this condition is a cause of many inflammatory and autoimmune diseases. Aegiceras corniculatum a mangrove plant has been using for many years for the treatment of many inflammatory and autoimmune diseases like atherosclerosis, rheumatoid arthritis, asthma and is well known as a folklore medicine constituting various novel chemical constituents. Methodology: Methanol and ethyl acetate extracts derived from A. corniculatum were evaluated against chronic inflammation by using cotton pellet induced granuloma and Adjuvant induced arthritis models in rats. Vascular permeability and leukocyte migration were studied in the presence of extracts. Results: In cotton pellet granuloma, both the methanol and ethanol extracts were found to highly effective in reducing granulomatous tissue formation in a dose dependent manner. These extracts also suppressed the paw thickness induced by using adjuvant in rat arthritis model, at maximum oral dose of 50 mg/kg methanol extract inhibited swelling in paw by 67%, whereas ethyl acetate extract caused 75% of inhibition in paw swelling at 200 mg/kg. Additionally, ethyl acetate extract has shown inhibition in leukocytes migration (63% at 50 mg/kg) against LTB4 and carrageenan. However, methanol extract failed to produce inhibitory effect against cell infiltration induced by LTB4. Interestingly, methanol and ethyl acetate extract has shown remarkable reduction in the acetic acid induced vascular permeability. Conclusion: A. corniculatum extracts has shown remarkable effect as an anti-arthritic and anti-inflammatory agent to combat with chronic inflammatory diseases, this study provides significant justification for its folklore medical use against rheumatism interfering with inflammatory and cellular immune responses. (author)

  3. Gastrointestinal symptoms, inflammation and hypoalbuminemia in chronic kidney disease patients: a cross-sectional study.

    Science.gov (United States)

    Zhang, Xuehan; Bansal, Nisha; Go, Alan S; Hsu, Chi-Yuan

    2015-12-11

    Few studies have focused on investigating hypoalbuminemia in patients during earlier stages of chronic kidney disease (CKD). In particular, little is known about the role of gastrointestinal (GI) symptoms. Our goal in this paper is to study how GI symptoms relate to serum albumin levels in CKD, especially in the context of and compared with inflammation. We performed a cross-sectional study of 3599 patients with chronic kidney disease enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study. All subjects were asked to complete the Modification of Diet in Renal Disease (MDRD) study patient symptom form. Our main predictor is GI symptom score. Serum level of C-reactive protein (CRP) was measured as well. Main outcome measures are serum albumin levels and prevalence of hypoalbuminemia. Of the participants assessed, mean serum albumin was 3.95 ± 0.46 g/dL; 12.7 % had hypoalbuminemia. Patients with lower estimated glomerular filtration rate (eGFR) were likely to have more GI symptoms (apparent at an eGFR Patients with worse GI symptoms had lower dietary protein intake. GI symptoms, like inflammation, were risk factors for lower serum albumin levels. However, adding GI symptom score or CRP into the multivariable regression analysis, did not attenuate the association between lower eGFR and lower albumin or hypoalbuminemia. Increased prevalence of GI symptoms become apparent among CKD patients at relatively high eGFR levels (45 ml/min/1.73 m(2)), long before ESRD. Patients with more severe GI symptoms scores are more likely to have hypoalbuminemia. But our data do not support GI symptoms/decreased protein intake or inflammation as being the main determinants of serum albumin level in CKD patients.

  4. A PAF receptor antagonist inhibits acute airway inflammation and late-phase responses but not chronic airway inflammation and hyperresponsiveness in a primate model of asthma

    Directory of Open Access Journals (Sweden)

    R. H. Gundel

    1992-01-01

    Full Text Available We have examined the effects of a PAF receptor antagonist, WEB 2170, on several indices of acute and chronic airway inflammation and associated changes in lung function in a primate model of allergic asthma. A single oral administration WEB 2170 provided dose related inhibition of the release of leukotriene C4 (LTC4 and prostaglandin D2 (PGD2 recovered and quantified in bronchoalveolar lavage (BAL fluid obtained during the acute phase response to inhaled antigen. In addition, oral WEB 2170 treatment in dual responder primates blocked the acute influx of neutrophils into the airways as well as the associated late-phase airway obstruction occurring 6 h after antigen inhalation. In contrast, a multiple dosing regime with WEB 2170 (once a day for 7 consecutive days failed to reduce the chronic airway inflammation (eosinophilic and associated airway hyperresponsiveness to inhaled methacholine that is characteristic of dual responder monkeys. Thus, we conclude that the generation of PAF following antigen inhalation contributes to the development of lipid mediators, acute airway inflammation and associated late-phase airway obstruction in dual responder primates; however, PAF does not play a significant role in the maintenance of chronic airway inflammation and associated airway hyperresponsiveness in this primate model.

  5. Gene expression profiling in autoimmune diseases: chronic inflammation or disease specific patterns?

    DEFF Research Database (Denmark)

    Bovin, Lone Frier; Brynskov, Jørn; Hegedüs, Laszlo

    2007-01-01

    A central issue in autoimmune disease is whether the underlying inflammation is a repeated stereotypical process or whether disease specific gene expression is involved. To shed light on this, we analysed whether genes previously found to be differentially regulated in rheumatoid arthritis (RA......) patients and healthy individuals were specific for the arthritic process or likewise altered in other chronic inflammatory diseases such as chronic autoimmune thyroiditis (Hashimoto's thyroiditis, HT) and inflammatory bowel disease (IBD). Using qPCR for 18 RA-discriminative genes, there were no significant...... immunoinflammatory diseases, but only if accompanied by pronounced systemic manifestations. This suggests that at least some of the genes activated in RA are predominantly or solely related to general and disease-nonspecific autoimmune processes....

  6. Inflammatory bowel disease: a model of chronic inflammation-induced cancer.

    Science.gov (United States)

    Yang, Guang-Yu; Taboada, Sofia; Liao, Jie

    2009-01-01

    Chronic inflammation is a well-recognized risk factor for the development of human cancer. Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is a typical longstanding inflammatory disease of the colon with increased risk for the development of colorectal carcinoma. Several molecular events involved in chronic inflammatory process may contribute to multistage progression of human cancer development, including the overproduction of reactive oxygen and nitrogen species, overproduction/activation of key arachidonic acid metabolites and cytokines/growth factors, and immunity system dysfunction. Multiple animal models of IBD have been established, and in general, these models can be mainly categorized into chemically induced, genetically engineered (transgenic or gene knock-out), spontaneous, and adoptive transferring animal models. This chapter mainly focuses on (1) epidemiologic and molecular evidence on IBD and risk of colorectal cancer, (2) molecular pathogenesis of IBD-induced carcinogenesis, and (3) modeling of IBD-induced carcinogenesis in rodents and its application.

  7. Chronic inflammation of the prostate type IV with respect to risk of prostate cancer

    Directory of Open Access Journals (Sweden)

    Antonio B. Porcaro

    2014-09-01

    Full Text Available Background: Chronic inflammatory infiltrate (CII might be involved in prostate cancer (PCA and benign hyperplasia (BPH; however, its significance is controversial. Chronic inflammatory prostatitis type IV is the most common non cancer diagnosis in men undergoing biopsy because of suspected PCA. Objective: To evaluate potential associations of coexistent CII and PCA in biopsy specimens after prostate assessment. Design, setting, and participants: Between January 2007 and December 2008, 415 consecutive patients who underwent prostate biopsy were retrospectively evaluated. The investigated variables included Age (years and PSA (ug/l; moreover, CII+, glandular atrophy (GA+, glandular hyperplasia (GH+, prostate Intraepithelial neoplasm (PIN+, atypical small acinar cell proliferation (ASAP+ and PCA positive cores (P+ were evaluated as categorical and continuous (proportion of positive cores. Outcome measurements and statistical analysis: Associations of CII+ and PCA risk were assessed by statistical methods. Results and limitations: In the patient population, a biopsy core positive for PCA was detected in 34.2% of cases and the rate of high grade PCA (HGPCA: bGS ! 8 resulted 4.82%. CII+ significantly and inversely associated with a positive biopsy core P+ (P < 0.0001; OR = 0.26 and HGPCA (P = 0.0005; OR = 0.05. Moreover, the associations indicated that patients with coexistent CII+ on needle biopsy were 74% less likely to have coexistent PCA than men without CII+ as well as 95% less likely to have HGPCA in the biopsy core than men without coexistent CII+. There were limits in our study which was single centre and included only one dedicated pathologist. Conclusions: There was an inverse association of chronic inflammation of the prostate type IV and risk of PCA; moreover, HGPCA was less likely to be detected in cancers associated with coexistent CII. In prostate microenvironment, prostate chronic inflammation may be protective; however, its role in

  8. Radiolabelled Interleukin-12, a new radiopharmaceutical for imaging chronic TH1-mediated inflammation

    International Nuclear Information System (INIS)

    Annovazzi, A.; Cornelissen, B.; Slegers, G.; D'Alessandria, C.; Bonanno, E.; Signore, A.

    2003-01-01

    Full text: Cytokines have been extensively used to image inflammatory processes (IL1, IL2, IL6, IL8 and others). In particular, for chronic inflammation, labelled IL2 has been successfully used although it binds to both T helper-1 (Th1) and T helper-2 (Th2) cells. In order to increase the specificity for the detection of Th1-mediated inflammation (i.e. organ specific autoimmune diseases), we considered the possibility to label the interleukin-12 (IL12), an heterodimeric cytokine which play a key role in the development of Th1 cells. Objectives: Aim of the present study was to label the Interleukin-12 with 123I and to test its potential as radiopharmaceutical to image chronic inflammatory disorders. Methods: IL12 was labelled with 123I using the IODOGEN method and purified by gel-filtration chromatography on PD10 columns. 123I-IL12 biodistribution was studied in normal NMRI mice at 1,2 and 4h after injection. A mouse model of autoimmune chronic colitis induced by intrarectal instillation of Trinitrobenzen sulfonic acid (TNBS) has been used for imaging purposes and, as controls, mice receiving 50% ethanol in phosphate buffer saline. Results: 123I-IL12 labelling efficiency ranged between 52-65%. Results of biodistribution studies showed a rapid plasma clearance and a main renal excretion route. No significant 123I-IL12 accumulation in major organs and tissues was observed. 123I-IL12 accumulated in areas of chronic inflamed colon as assessed by histological examination. No significant 123I-IL12 uptake is detectable in mice with acute colitis, confirming the specificity of 123IIL12 binding on its receptors expressed on T-lymphocytes. Conclusions: We conclude that this cytokine could be used for the in vivo imaging of Th1 mediated inflammatory processes. (author)

  9. Periodontal Disease: A Covert Source of Inflammation in Chronic Kidney Disease Patients

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    Gener Ismail

    2013-01-01

    Full Text Available The prevalence of atherosclerotic complications (myocardial infarction, stroke, and sudden death is increased in end-stage renal disease (ESRD patients, especially in haemodialysis patients. Increasing evidence suggests that both in general population and in dialysis patients, systemic inflammation plays a dominant role in the pathogenesis of atherosclerotic complications. In general population, also, evidence shows that moderate to severe periodontitis can contribute to inflammatory burden by increasing serum CRP levels and may increase the prevalence of atherosclerotic events. Moreover, the results of some new interventional studies reveal that effective phase I periodontal therapy may decrease serum CRP levels, the most important acute phase protein, monitored as a systemic marker of inflammation and endothelial dysfunction as well, used as an initial predictor of atherosclerotic events. Considering that moderate to severe periodontal diseases have a higher prevalence in CKD and in dialysis population and that periodontal examination is not part of the standard medical assessment, destructive periodontitis might be an ignored source of systemic inflammation in end-stage renal disease patients and may add to the chronic inflammatory status in CKD.

  10. Chronic inflammation-elicited liver progenitor cell conversion to liver cancer stem cell with clinical significance.

    Science.gov (United States)

    Li, Xiao-Feng; Chen, Cheng; Xiang, Dai-Min; Qu, Le; Sun, Wen; Lu, Xin-Yuan; Zhou, Teng-Fei; Chen, Shu-Zhen; Ning, Bei-Fang; Cheng, Zhuo; Xia, Ming-Yang; Shen, Wei-Feng; Yang, Wen; Wen, Wen; Lee, Terence Kin Wah; Cong, Wen-Ming; Wang, Hong-Yang; Ding, Jin

    2017-12-01

    The substantial heterogeneity and hierarchical organization in liver cancer support the theory of liver cancer stem cells (LCSCs). However, the relationship between chronic hepatic inflammation and LCSC generation remains obscure. Here, we observed a close correlation between aggravated inflammation and liver progenitor cell (LPC) propagation in the cirrhotic liver of rats exposed to diethylnitrosamine. LPCs isolated from the rat cirrhotic liver initiated subcutaneous liver cancers in nonobese diabetic/severe combined immunodeficient mice, suggesting the malignant transformation of LPCs toward LCSCs. Interestingly, depletion of Kupffer cells in vivo attenuated the LCSC properties of transformed LPCs and suppressed cytokeratin 19/Oval cell 6-positive tumor occurrence. Conversely, LPCs cocultured with macrophages exhibited enhanced LCSC properties. We further demonstrated that macrophage-secreted tumor necrosis factor-α triggered chromosomal instability in LPCs through the deregulation of ubiquitin D and checkpoint kinase 2 and enhanced the self-renewal of LPCs through the tumor necrosis factor receptor 1/Src/signal transducer and activator of transcription 3 pathway, which synergistically contributed to the conversion of LPCs to LCSCs. Clinical investigation revealed that cytokeratin 19/Oval cell 6-positive liver cancer patients displayed a worse prognosis and exhibited superior response to sorafenib treatment. Our results not only clarify the cellular and molecular mechanisms underlying the inflammation-mediated LCSC generation but also provide a molecular classification for the individualized treatment of liver cancer. (Hepatology 2017;66:1934-1951). © 2017 by the American Association for the Study of Liver Diseases.

  11. Changing glucocorticoid action: 11β-hydroxysteroid dehydrogenase type 1 in acute and chronic inflammation.

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    Chapman, Karen E; Coutinho, Agnes E; Zhang, Zhenguang; Kipari, Tiina; Savill, John S; Seckl, Jonathan R

    2013-09-01

    Since the discovery of cortisone in the 1940s and its early success in treatment of rheumatoid arthritis, glucocorticoids have remained the mainstay of anti-inflammatory therapies. However, cortisone itself is intrinsically inert. To be effective, it requires conversion to cortisol, the active glucocorticoid, by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Despite the identification of 11β-HSD in liver in 1953 (which we now know to be 11β-HSD1), its physiological role has been little explored until recently. Over the past decade, however, it has become apparent that 11β-HSD1 plays an important role in shaping endogenous glucocorticoid action. Acute inflammation is more severe with 11β-HSD1-deficiency or inhibition, yet in some inflammatory settings such as obesity or diabetes, 11β-HSD1-deficiency/inhibition is beneficial, reducing inflammation. Current evidence suggests both beneficial and detrimental effects may result from 11β-HSD1 inhibition in chronic inflammatory disease. Here we review recent evidence pertaining to the role of 11β-HSD1 in inflammation. This article is part of a Special Issue entitled 'CSR 2013'. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Changing glucocorticoid action: 11β-Hydroxysteroid dehydrogenase type 1 in acute and chronic inflammation

    Science.gov (United States)

    Chapman, Karen E.; Coutinho, Agnes E.; Zhang, Zhenguang; Kipari, Tiina; Savill, John S.; Seckl, Jonathan R.

    2013-01-01

    Since the discovery of cortisone in the 1940s and its early success in treatment of rheumatoid arthritis, glucocorticoids have remained the mainstay of anti-inflammatory therapies. However, cortisone itself is intrinsically inert. To be effective, it requires conversion to cortisol, the active glucocorticoid, by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Despite the identification of 11β-HSD in liver in 1953 (which we now know to be 11β-HSD1), its physiological role has been little explored until recently. Over the past decade, however, it has become apparent that 11β-HSD1 plays an important role in shaping endogenous glucocorticoid action. Acute inflammation is more severe with 11β-HSD1-deficiency or inhibition, yet in some inflammatory settings such as obesity or diabetes, 11β-HSD1-deficiency/inhibition is beneficial, reducing inflammation. Current evidence suggests both beneficial and detrimental effects may result from 11β-HSD1 inhibition in chronic inflammatory disease. Here we review recent evidence pertaining to the role of 11β-HSD1 in inflammation. This article is part of a Special Issue entitled ‘CSR 2013’. PMID:23435016

  13. Sub-chronic lung inflammation after airway exposures to Bacillus thuringiensis biopesticides in mice

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    Barfod Kenneth K

    2010-09-01

    exposures to commercial Bt based biopesticides can induce sub-chronic lung inflammation in mice, which may be the first step in the development of chronic lung diseases. Inhalation of Bt aerosols does not induce airway irritation, which could explain why workers may be less inclined to use a filter mask during the application process, and are thereby less protected from exposure to Bt spores.

  14. The relationship between visfatin, liver inflammation, and acute phase reactants in chronic viral hepatitis B.

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    Yüksel, Enver; Akbal, Erdem; Koçak, Erdem; Akyürek, Ömer; Köklü, Seyfettin; Ekiz, Fuat; Yılmaz, Barış

    2016-09-01

    Chronic viral hepatitis B (CHB) is an important cause of morbidity and mortality. Adipokine stimulation might play an important role in the pathogenesis of chronic inflammation. The aim of this study was to evaluate serum visfatin concentrations and the relationship between visfatin, fibrosis, liver inflammation, and acute phase reactants in CHB patients.The sampling universe of the study consisted of 41 CHB patients and 25 healthy controls. All patients had positive hepatitis B surface antigen (Hepatitis e antigen (HBeAg) positive n: 7, n: 34 HBeAg negative) for at least 6 months and detectable serum HBV DNA. Serum visfatin concentrations were significantly higher in the CHB patients [18.0 ± 10.9 ng dL(-1)] than in the healthy controls [9.4 ± 1.6 ng dL(-1)] [P < 0.001]. On the other hand, fibrinogen and haptoglobin concentrations were significantly lower in CHB patients. A strong negative correlation was observed between serum visfatin concentration, haptoglobin, and fibrinogen levels; however, there was no significant correlation between visfatin, glucose, alanine aminotransferase, aspartate aminotransferase, BMI, Knodell score, fibrosis score, hepatitis B virus DNA, sedimentation, and C-reactive protein. Visfatin concentrations were elevated and visfatin was negatively correlated with haptoglobin and fibrinogen levels in CHB patients.

  15. Diethylcarbamazine Reduces Chronic Inflammation and Fibrosis in Carbon Tetrachloride- (CCl4- Induced Liver Injury in Mice

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    Sura Wanessa Santos Rocha

    2014-01-01

    Full Text Available This study investigated the anti-inflammatory effects of DEC on the CCl4-induced hepatotoxicity in C57BL/6 mice. Chronic inflammation was induced by i.p. administration of CCl4 0.5 μL/g of body weight through two injections a week for 6 weeks. DEC (50 mg/kg was administered by gavage for 12 days before finishing the CCl4 induction. Histological analyses of the DEC-treated group exhibited reduced inflammatory process and prevented liver necrosis and fibrosis. Immunohistochemical and immunofluorescence analyses of the DEC-treated group showed reduced COX-2, IL1β, MDA, TGF-β, and αSMA immunopositivity, besides exhibiting decreased IL1β, COX-2, NFκB, IFNγ, and TGFβ expressions in the western blot analysis. The DEC group enhanced significantly the IL-10 expression. The reduction of hepatic injury in the DEC-treated group was confirmed by the COX-2 and iNOS mRNA expression levels. Based on the results of the present study, DEC can be used as a potential anti-inflammatory drug for chronic hepatic inflammation.

  16. Influence of Chronic Moderate Sleep Restriction and Exercise on Inflammation and Carcinogenesis in Mice

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    Zielinski, Mark R.; Davis, J. Mark; Fadel, James R.; Youngstedt, Shawn D.

    2013-01-01

    The effects of chronic moderate sleep restriction and exercise training on carcinogenesis were examined in adenomatous polyposis coli multiple intestinal neoplasma (APC Min+/-) mice, a genetic strain which is predisposed to developing adenomatous polyposis. The mice were randomized to one of four 11 week treatments in a 2×2 design involving sleep restriction (by 4 h/day) vs. normal sleep and exercise training (1 h/day) vs. sedentary control. Wild-type control mice underwent identical experimental treatments. Compared with the wild-type mice, APC Min+/- mice had disrupted hematology and enhanced pro-inflammatory cytokine production from peritoneal exudate cells. Among the APC Min+/- mice, consistent interactions of sleep loss and exercise were found for measures of polyp formation, inflammation, and hematology. Sleep loss had little effect on these variables under sedentary conditions, but sleep loss had clear detrimental effects under exercise conditions. Exercise training resulted in improvements in these measures under normal sleep conditions, but exercise tended to elicit no effect or to exacerbate the effects of sleep restriction. Significant correlations of inflammation with polyp burden were observed. Among wild-type mice, similar, but less consistent interactions of sleep restriction and exercise were found. These data suggest that the benefits of exercise on carcinogenesis and immune function were impaired by chronic moderate sleep restriction, and that harmful effects of sleep restriction were generally realized only in the presence of exercise. PMID:22433899

  17. Diet and Inflammation in Alzheimer's Disease and Related Chronic Diseases: A Review.

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    Gardener, Samantha L; Rainey-Smith, Stephanie R; Martins, Ralph N

    2016-01-01

    Inflammation is one of the pathological features of the neurodegenerative disease, Alzheimer's disease (AD). A number of additional disorders are likewise associated with a state of chronic inflammation, including obesity, cardiovascular disease, and type-2 diabetes, which are themselves risk factors for AD. Dietary components have been shown to modify the inflammatory process at several steps of the inflammatory pathway. This review aims to evaluate the published literature on the effect of consumption of pro- or anti-inflammatory dietary constituents on the severity of both AD pathology and related chronic diseases, concentrating on the dietary constituents of flavonoids, spices, and fats. Diet-based anti-inflammatory components could lead to the development of potent novel anti-inflammatory compounds for a range of diseases. However, further work is required to fully characterize the therapeutic potential of such compounds, including gaining an understanding of dose-dependent relationships and limiting factors to effectiveness. Nutritional interventions utilizing anti-inflammatory foods may prove to be a valuable asset in not only delaying or preventing the development of age-related neurodegenerative diseases such as AD, but also treating pre-existing conditions including type-2 diabetes, cardiovascular disease, and obesity.

  18. Mast cells in chronic inflammation, pelvic pain and depression in women.

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    Graziottin, Alessandra; Skaper, Stephen D; Fusco, Mariella

    2014-07-01

    Inflammatory and neuroinflammatory processes are increasingly recognized as critical pathophysiologic steps in the development of multiple chronic diseases and in the etiology of persistent pain and depression. Mast cells are immune cells now viewed as cellular sensors in inflammation and immunity. When stimulated, mast cells release an array of mediators to orchestrate an inflammatory response. These mediators can directly initiate tissue responses on resident cells, and may also regulate the activity of other immune cells, including central microglia. New evidence supports the involvement of peripheral and central mast cells in the development of pain processes as well as in the transition from acute, to chronic and neuropathic pain. That behavioral and endocrine states can increase the number and activation of peripheral and brain mast cells suggests that mast cells represent the immune cells that peripherally and centrally coordinate inflammatory processes in neuropsychiatric diseases such as depression and anxiety which are associated with chronic pelvic pain. Given that increasing evidence supports the activated mast cell as a director of common inflammatory pathways/mechanisms contributing to chronic and neuropathic pelvic pain and comorbid neuropsychiatric diseases, mast cells may be considered a viable target for the multifactorial management of both pain and depression.

  19. Systemic inflammation in chronic obstructive pulmonary disease and lung cancer: common driver of pulmonary cachexia?

    Science.gov (United States)

    Ceelen, Judith J M; Langen, Ramon C J; Schols, Annemie M W J

    2014-12-01

    In this article, a putative role of systemic inflammation as a driver of pulmonary cachexia induced by either chronic obstructive pulmonary disease or nonsmall cell lung cancer is reviewed. Gaps in current translational research approaches are discussed and alternative strategies are proposed to provide new insights. Activation of the ubiquitin proteasome system has generally been considered a cause of pulmonary cachexia, but current animal models lack specificity and evidence is lacking in nonsmall cell lung cancer and conflicting in chronic obstructive pulmonary disease patients. Recent studies have shown activation of the autophagy-lysosome pathway in both nonsmall cell lung cancer and chronic obstructive pulmonary disease. Myonuclear loss, as a consequence of increased apoptotic events in myofibers, has been suggested in cancer-cachexia-associated muscle atrophy. Plasma transfer on myotube cultures can be used to detect early inflammatory signals in patients and presence of atrophy-inducing activity within the circulation. Comparative clinical research between nonsmall cell lung cancer and chronic obstructive pulmonary disease in different disease stages is useful to unravel disease-specific versus common denominators of pulmonary cachexia.

  20. Association of Mucosal Organisms with Patterns of Inflammation in Chronic Rhinosinusitis.

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    Thanit Chalermwatanachai

    Full Text Available Chronic rhinosinusitis is a multifactorial process disease in which bacterial infection or colonization may play an important role in the initiation or persistence of inflammatory response. The association between mucosal bacteria presence and inflammatory patterns has only been partially explored.To demonstrate specific mucosal microorganisms possible association with inflammatory patterns.We collected nasal polyps or sinus tissues from a clinical selection of six patient groups with defined sinus disease using tissue biomarkers. In the tissues, we detected bacteria using peptide nucleic acid fluorescence in situ hybridization (PNA-FISH.After reviewing a total of 115 samples (15-20 samples per group, the mucosal presence of Staphylococcus aureus was correlated with IL-5 and SE-IgE positive chronic rhinosinusitis with nasal polyps and nasal polyps from cystic fibrosis patients. Chronic rhinosinusitis without nasal polyps with TNFα >20 pg/ml was associated with the mucosal presence of Pseudomonas aeruginosa.This study identifies the relationship between intramucosal microbes and inflammatory patterns, suggesting that bacteria may affect the type of inflammation in chronic rhinosinusitis. Additional investigation is needed to further identify the nature of the relationship.

  1. Histologic and biochemical alterations predict pulmonary mechanical dysfunction in aging mice with chronic lung inflammation.

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    Christopher B Massa

    2017-08-01

    Full Text Available Both aging and chronic inflammation produce complex structural and biochemical alterations to the lung known to impact work of breathing. Mice deficient in surfactant protein D (Sftpd develop progressive age-related lung pathology characterized by tissue destruction/remodeling, accumulation of foamy macrophages and alteration in surfactant composition. This study proposes to relate changes in tissue structure seen in normal aging and in chronic inflammation to altered lung mechanics using a computational model. Alterations in lung function in aging and Sftpd -/- mice have been inferred from fitting simple mechanical models to respiratory impedance data (Zrs, however interpretation has been confounded by the simultaneous presence of multiple coexisting pathophysiologic processes. In contrast to the inverse modeling approach, this study uses simulation from experimental measurements to recapitulate how aging and inflammation alter Zrs. Histologic and mechanical measurements were made in C57BL6/J mice and congenic Sftpd-/- mice at 8, 27 and 80 weeks of age (n = 8/group. An anatomic computational model based on published airway morphometry was developed and Zrs was simulated between 0.5 and 20 Hz. End expiratory pressure dependent changes in airway caliber and recruitment were estimated from mechanical measurements. Tissue elements were simulated using the constant phase model of viscoelasticity. Baseline elastance distribution was estimated in 8-week-old wild type mice, and stochastically varied for each condition based on experimentally measured alteration in elastic fiber composition, alveolar geometry and surfactant composition. Weighing reduction in model error against increasing model complexity allowed for identification of essential features underlying mechanical pathology and their contribution to Zrs. Using a maximum likelihood approach, alteration in lung recruitment and diminished elastic fiber density were shown predictive of mechanical

  2. Metabolic syndrome criteria as predictors of insulin resistance, inflammation and mortality in chronic hemodialysis patients.

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    Vogt, Barbara Perez; Souza, Priscilla L; Minicucci, Marcos Ferreira; Martin, Luis Cuadrado; Barretti, Pasqual; Caramori, Jacqueline Teixeira

    2014-10-01

    Abstract Background: Chronic kidney disease (CKD) and metabolic syndrome are characterized by overlapping disorders, including glucose intolerance, hypertension, dyslipidemia, and, in some cases, obesity. However, there are no specific criteria for the diagnosis of metabolic syndrome in CKD. Metabolic syndrome can also be associated with increased risk of mortality. Some traditional risk factors may protect dialysis patients from mortality, known as "reverse epidemiology." Metabolic syndrome might undergo reverse epidemiology. The objectives were to detect differences in frequency and metabolic characteristics associated with three sets of diagnostic criteria for metabolic syndrome, to evaluate the accuracy of insulin resistance (IR) and inflammation to identify patients with metabolic syndrome, and to investigate the effects of metabolic syndrome by three sets of diagnostic criteria on mortality in chronic hemodialysis patients. An observational study was conducted. Diagnostic criteria for metabolic syndrome proposed by National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III), International Diabetes Federation (IDF), and Harmonizing the Metabolic Syndrome (HMetS) statement were applied to 98 hemodialysis patients. The prevalence of metabolic syndrome was 51%, 66.3%, and 75.3% according to NCEP ATP III, IDF, and HMetS criteria, respectively. Diagnosis of metabolic syndrome by HMetS was simultaneously capable of revealing both inflammation and IR, whereas NCEP ATP III and IDF criteria were only able to identify IR. Mortality risk increased in the presence of metabolic syndrome regardless of the criteria used. The prevalence of metabolic syndrome in hemodialysis varies according to the diagnostic criteria used. IR and inflammation predict metabolic syndrome only when diagnosed by HMetS criteria. HMetS was the diagnostic criteria that can predict the highest risk of mortality.

  3. Chronic granulomatous inflammation in teleost fish Piaractus mesopotamicus: histopathology model study

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    Wilson G Manrique

    2017-01-01

    Full Text Available Objective. This study evaluated the cell kinetic and formation of granuloma during chronic inflammation induced by Bacillus Calmette-Guérin (BCG in the skeletal muscle of Piaractus mesopotamicus, as a histopathology model to study innate immunity. Materials and methods. Sixty fish were divided in two groups: BCG-inoculated and non-inoculated fish and the inflammatory response analyzed 3, 7, 14, 21 and 33 days post-inoculation (DPI by histopathology after hematoxylin-eosin and Ziehl-Neelsen staining. Results. 3 DPI of BCG showed a diffuse inflammatory reaction mostly composed by mononuclear cells. The inflammation continued diffuse 7 DPI initiating the cellular organization surrounding the inoculum and have continued at 14 DPI with discrete presence of epithelioid-like type cells with acidophilic cytoplasm and floppy chromatin. Higher cellular organization (21 DPI surrounding the granuloma with intense peripheral mononuclear inflammatory infiltrate and nevertheless, an increase in the number of fibroblasts and macrophage-like cells was observed. The inflammatory process became less diffuse 33 DPI with formation of small amount of granuloma surrounded by the same type of reaction found in bigger granuloma. Both the young and old granuloma presented typical characteristic around the inoculum composed by a layer of epithelioid-like type cells, besides macrophages, some lymphocytes and abundant fibroblasts. Conclusions. This study showed the feasibility in the use of pacus to study chronic granulomatous inflammatory response induced by BCG, characterized by changes in the kinetics of inflammatory cells in skeletal muscle classifying as immune-epithelioid type, similar to granulomatous inflammation caused by M. marinum in teleost fish.

  4. Haemophilus influenzae from Patients with Chronic Obstructive Pulmonary Disease Exacerbation Induce More Inflammation than Colonizers

    Science.gov (United States)

    Chin, Cecilia L.; Manzel, Lori J.; Lehman, Erin E.; Humlicek, Alicia L.; Shi, Lei; Starner, Timothy D.; Denning, Gerene M.; Murphy, Timothy F.; Sethi, Sanjay; Look, Dwight C.

    2005-01-01

    Rationale: Airway infection with Haemophilus influenzae causes airway inflammation, and isolation of new strains of this bacteria is associated with increased risk of exacerbations in patients with chronic obstructive pulmonary disease (COPD). Objective: To determine whether strains of H. influenzae associated with exacerbations cause more inflammation than strains that colonize the airways of patients with COPD. Methods: Exacerbation strains of H. influenzae were isolated from patients during exacerbation of clinical symptoms with subsequent development of a homologous serum antibody response and were compared with colonization strains that were not associated with symptom worsening or an antibody response. Bacterial strains were compared using an in vivo mouse model of airway infection and in vitro cell culture model of bacterial adherence and defense gene and signaling pathway activation in primary human airway epithelial cells. Results: H. influenzae associated with exacerbations caused more airway neutrophil recruitment compared with colonization strains in the mouse model of airway bacterial infection. Furthermore, exacerbation strains adhered to epithelial cells in significantly higher numbers and induced more interleukin-8 release after interaction with airway epithelial cells. This effect was likely mediated by increased activation of the nuclear factor-κB and p38 mitogen-activated protein kinase signaling pathways. Conclusions: The results indicate that H. influenzae strains isolated from patients during COPD exacerbations often induce more airway inflammation and likely have differences in virulence compared with colonizing strains. These findings support the concept that bacteria infecting the airway during COPD exacerbations mediate increased airway inflammation and contribute to decreased airway function. PMID:15805181

  5. Chronic antidepressant treatments resulted in altered expression of genes involved in inflammation in the rat hypothalamus.

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    Alboni, Silvia; Benatti, Cristina; Montanari, Claudia; Tascedda, Fabio; Brunello, Nicoletta

    2013-12-05

    To gain insight into the possible immune targets of antidepressant, we evaluated the expression of several inflammatory mediators in the hypothalamus of rats chronically (28 days) treated with the serotonin selective reuptake inhibitor fluoxetine (5mg/kg, i.p.) or the tricyclic compound imipramine (15 mg/kg, i.p.). We focused our attention on the hypothalamus as it plays a key role in determining many of the somatic symptoms experienced by depressed patients. This brain region, critical also for expression of motivated behaviours, participates in the control of the hypothalamic-pituitary-adrenal axis activity and in stress response as well as coordinates physiological functions such as sleep and food intake that have been found altered in a high percentage of depressed patients. Notably, hypothalamus is a key structure for brain cytokine expression and function as it integrates signals from the neuro, immune, endocrine systems. By means of quantitative Real Time PCR experiments we demonstrated that a chronic treatment with either fluoxetine or imipramine resulted in a reduction of IL-6 and IFN-γ mRNAs and increased IL-4 mRNA expression in the rat hypothalamus. Moreover, we demonstrated that hypothalamic expression of members of IL-18 system was differentially affected by chronic antidepressant treatments. Chronically administered fluoxetine decreased IL-8 and CX3CL1 hypothalamic expression, while a chronic treatment with imipramine decreased p11 mRNA. Our data suggest that a shift in the balance of the inflammation toward an anti-inflammatory state in the hypothalamus may represent a common mechanism of action of both the chronic treatments with fluoxetine and imipramine. © 2013 Published by Elsevier B.V.

  6. The Changes of Energy Interactions between Nucleus Function and Mitochondria Functions Causing Transmutation of Chronic Inflammation into Cancer Metabolism.

    Science.gov (United States)

    Ponizovskiy, Michail R

    2016-01-01

    Interactions between nucleus and mitochondria functions induce the mechanism of maintenance stability of cellular internal energy according to the first law of thermodynamics in able-bodied cells and changes the mechanisms of maintenance stability of cellular internal energy creating a transition stationary state of ablebodied cells into quasi-stationary pathologic states of acute inflammation transiting then into chronic inflammation and then transmuting into cancer metabolism. The mechanisms' influences of intruding etiologic pathologic agents (microbe, virus, etc.) lead to these changes of energy interactions between nucleus and mitochondria functions causing general acute inflammation, then passing into local chronic inflammation, and reversing into cancer metabolism transmutation. Interactions between biochemical processes and biophysical processes of cellular capacitors' operations create a supplementary mechanism of maintenance stability of cellular internal energy in the norm and in pathology. Discussion of some scientific works eliminates doubts of the authors of these works.

  7. Inflammation and nutritional status assessment by malnutrition inflammation score and its outcome in pre-dialysis chronic kidney disease patients.

    Science.gov (United States)

    Jagadeswaran, D; Indhumathi, E; Hemamalini, A J; Sivakumar, V; Soundararajan, P; Jayakumar, M

    2018-01-09

    Malnutrition-inflammation complex syndrome (MICS), hyperhomocysteinemia, calcium and phosphate levels derangement have been predicted as important contributing factors for the progression of cardiovascular burden. Among patients with earlier stage of CKD, hypoalbuminaemia and inflammation deliberated as non-traditional cardiovascular risk factors, which add more burden to circulatory disease, mortality and rapid advancement to CKD stage 5. The aim of the study is to evaluate inflammation and nutritional status of CKD patients not on dialysis using Malnutrition inflammation score (MIS) and to verify the association with mortality in the follow-up period. In this prospective cohort study 129 (66 males, 63 females) pre-dialysis CKD patients enrolled between June 2013 to August 2014 and censored until March 2017. Malnutrition and Inflammation assessed using Malnutrition inflammation score. Blood urea nitrogen, serum creatinine, albumin, Interleukin - 6, highly sensitive C reactive protein (hsCRP), total cholesterol and anthropometric data were analyzed. The Malnutrition inflammation score in pre-dialysis CKD patients ranged from 0 to 18 with the median score of two. During 36 or more months of follow-up, there were 30 (23.2%) deaths, 35 (27%) patients initiated on hemodialysis, one (0.7%) patient was initiated on peritoneal dialysis, two (1.4%) patients underwent renal transplantation and two (1.4%) patients were lost for follow-up. In this study, 33% had varying degree of malnutrition and inflammation. Patients who had MIS ≥7 had significant increase in IL-6 (p = 0.003) and HsCRP levels (p nutritional status and inflammation using MIS regularly to prevent malnutrition and its associated complications through appropriate medical and nutritional intervention. Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  8. Cigarette smoke-induced collagen destruction; key to chronic neutrophilic airway inflammation?

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    Saskia A Overbeek

    Full Text Available BACKGROUND: Cigarette smoking induces inflammatory responses in all smokers and is the major risk factor for lung disease such as chronic obstructive pulmonary disease (COPD. In this progressive disease, chronic inflammation in the lung contributes to lung tissue destruction leading to the formation of chemotactic collagen fragments such as N-acetylated Proline-Glycine-Proline (N-ac-PGP. The generation of this tripeptide is mediated by a multistep pathway involving matrix metalloproteases (MMPs 8 and 9 and prolyl endopeptidase (PE. Here we investigated whether cigarette smoke extract (CSE stimulates human PMNs to breakdown whole matrix collagen leading to the generation of the chemotactic collagen fragment N-ac-PGP. METHODOLOGY/PRINCIPAL FINDINGS: Incubating PMNs with CSE led to the release of chemo-attractant CXCL8 and proteases MMP8 and MMP9. PMNs constitutively expressed PE activity as well as PE protein. Incubating CSE-primed PMNs with collagen resulted in collagen breakdown and in N-ac-PGP generation. Incubation of PMNs with the tripeptide N-ac-PGP resulted in the release of CXCL8, MMP8 and MMP9. Moreover, we tested whether PMNs from COPD patients are different from PMNs from healthy donors. Here we show that the intracellular basal PE activity of PMNs from COPD patients increased 25-fold compared to PMNs from healthy donors. Immunohistological staining of human lung tissue for PE showed that besides neutrophils, macrophages and epithelial cells express PE. CONCLUSIONS: This study indicates that neutrophils activated by cigarette smoke extract can breakdown collagen into N-ac-PGP and that this collagen fragment itself can activate neutrophils, which may lead in vivo to a self-propagating cycle of neutrophil infiltration, chronic inflammation and lung emphysema. MMP-, PE- or PGP-inhibitors can serve as an attractive therapeutic target and may open new avenues towards effective treatment of COPD.

  9. High dietary fiber intake is associated with decreased inflammation and all-cause mortality in patients with chronic kidney disease.

    Science.gov (United States)

    Krishnamurthy, Vidya M Raj; Wei, Guo; Baird, Bradley C; Murtaugh, Maureen; Chonchol, Michel B; Raphael, Kalani L; Greene, Tom; Beddhu, Srinivasan

    2012-02-01

    Chronic kidney disease is considered an inflammatory state and a high fiber intake is associated with decreased inflammation in the general population. Here, we determined whether fiber intake is associated with decreased inflammation and mortality in chronic kidney disease, and whether kidney disease modifies the associations of fiber intake with inflammation and mortality. To do this, we analyzed data from 14,543 participants in the National Health and Nutrition Examination Survey III. The prevalence of chronic kidney disease (estimated glomerular filtration rate less than 60 ml/min per 1.73 m(2)) was 5.8%. For each 10-g/day increase in total fiber intake, the odds of elevated serum C-reactive protein levels were decreased by 11% and 38% in those without and with kidney disease, respectively. Dietary total fiber intake was not significantly associated with mortality in those without but was inversely related to mortality in those with kidney disease. The relationship of total fiber with inflammation and mortality differed significantly in those with and without kidney disease. Thus, high dietary total fiber intake is associated with lower risk of inflammation and mortality in kidney disease and these associations are stronger in magnitude in those with kidney disease. Interventional trials are needed to establish the effects of fiber intake on inflammation and mortality in kidney disease.

  10. Keloid and Hypertrophic Scars Are the Result of Chronic Inflammation in the Reticular Dermis

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    Rei Ogawa

    2017-03-01

    Full Text Available Keloids and hypertrophic scars are caused by cutaneous injury and irritation, including trauma, insect bite, burn, surgery, vaccination, skin piercing, acne, folliculitis, chicken pox, and herpes zoster infection. Notably, superficial injuries that do not reach the reticular dermis never cause keloidal and hypertrophic scarring. This suggests that these pathological scars are due to injury to this skin layer and the subsequent aberrant wound healing therein. The latter is characterized by continuous and histologically localized inflammation. As a result, the reticular layer of keloids and hypertrophic scars contains inflammatory cells, increased numbers of fibroblasts, newly formed blood vessels, and collagen deposits. Moreover, proinflammatory factors, such as interleukin (IL-1α, IL-1β, IL-6, and tumor necrosis factor-α are upregulated in keloid tissues, which suggests that, in patients with keloids, proinflammatory genes in the skin are sensitive to trauma. This may promote chronic inflammation, which in turn may cause the invasive growth of keloids. In addition, the upregulation of proinflammatory factors in pathological scars suggests that, rather than being skin tumors, keloids and hypertrophic scars are inflammatory disorders of skin, specifically inflammatory disorders of the reticular dermis. Various external and internal post-wounding stimuli may promote reticular inflammation. The nature of these stimuli most likely shapes the characteristics, quantity, and course of keloids and hypertrophic scars. Specifically, it is likely that the intensity, frequency, and duration of these stimuli determine how quickly the scars appear, the direction and speed of growth, and the intensity of symptoms. These proinflammatory stimuli include a variety of local, systemic, and genetic factors. These observations together suggest that the clinical differences between keloids and hypertrophic scars merely reflect differences in the intensity, frequency

  11. Chronic brain inflammation leads to a decline in hippocampal NMDA-R1 receptors

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    Hauss-Wegrzyniak Beatrice

    2004-07-01

    Full Text Available Abstract Background Neuroinflammation plays a prominent role in the progression of Alzheimer's disease and may be responsible for degeneration in vulnerable regions such as the hippocampus. Neuroinflammation is associated with elevated levels of extracellular glutamate and potentially an enhanced stimulation of glutamate N-methyl-D-aspartate receptors. This suggests that neurons that express these glutamate receptors might be at increased risk of degeneration in the presence of chronic neuroinflammation. Methods We have characterized a novel model of chronic brain inflammation using a slow infusion of lipopolysaccharide into the 4th ventricle of rats. This model reproduces many of the behavioral, electrophysiological, neurochemical and neuropathological changes associated with Alzheimer's disease. Results The current study demonstrated that chronic neuroinflammation is associated with the loss of N-methyl-D-aspartate receptors, as determined both qualitatively by immunohistochemistry and quantitatively by in vitro binding studies using [3H]MK-801, within the hippocampus and entorhinal cortex. Conclusion The gradual loss of function of this critical receptor within the temporal lobe region may contribute to some of the cognitive deficits observed in patients with Alzheimer's disease.

  12. Chronic inflammation predicts long-term mortality in patients with Raynaud's phenomenon.

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    Mueller, M; Gschwandtner, M E; Gamper, J; Giurgea, G-A; Kiener, H P; Perkmann, T; Koppensteiner, R; Schlager, O

    2018-03-01

    Subclinical chronic inflammation could be the driving force behind the recently revealed association between abnormal nailfold capillaries as well as autoantibodies and long-term mortality in patients with incipient Raynaud's phenomenon. Whether laboratory markers that reflect a chronic inflammatory process are directly related to mortality in Raynaud's phenomenon is not known. In total, 2958 patients with incipient Raynaud's phenomenon without previously known connective tissue disease (CTD) were enrolled. At their initial presentation, laboratory tests for C-reactive protein (CRP), leucocytes, fibrinogen and the haemoglobin concentration were obtained. In addition, nailfold capillaries and antinuclear antibodies (ANA) were assessed. Patients' mortality was recorded through a median follow-up period of 9.3 years. Baseline CRP, fibrinogen and haemoglobin concentration were associated with long-term mortality in an individual analysis of patients with incipient Raynaud's phenomenon. In a multivariable model including patients' age, nailfold capillaries and ANA, a low haemoglobin concentration remained independently related to future mortality. Amongst potential predictors for mortality in patients with Raynaud's phenomenon, a low haemoglobin concentration was most strongly related to patients' mortality risk. In Raynaud's phenomenon, laboratory markers that can be attributed to a chronic inflammatory state independently yield prognostic information in addition to the presence of abnormal nailfold capillaries and ANA. Amongst all prognostic markers, the haemoglobin concentration is most strongly related to patients' mortality in Raynaud's phenomenon. © 2017 The Association for the Publication of the Journal of Internal Medicine.

  13. Acute and chronic effects of treatment with mesenchymal stromal cells on LPS-induced pulmonary inflammation, emphysema and atherosclerosis development.

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    P Padmini S J Khedoe

    Full Text Available COPD is a pulmonary disorder often accompanied by cardiovascular disease (CVD, and current treatment of this comorbidity is suboptimal. Systemic inflammation in COPD triggered by smoke and microbial exposure is suggested to link COPD and CVD. Mesenchymal stromal cells (MSC possess anti-inflammatory capacities and MSC treatment is considered an attractive treatment option for various chronic inflammatory diseases. Therefore, we investigated the immunomodulatory properties of MSC in an acute and chronic model of lipopolysaccharide (LPS-induced inflammation, emphysema and atherosclerosis development in APOE*3-Leiden (E3L mice.Hyperlipidemic E3L mice were intranasally instilled with 10 μg LPS or vehicle twice in an acute 4-day study, or twice weekly during 20 weeks Western-type diet feeding in a chronic study. Mice received 0.5x106 MSC or vehicle intravenously twice after the first LPS instillation (acute study or in week 14, 16, 18 and 20 (chronic study. Inflammatory parameters were measured in bronchoalveolar lavage (BAL and lung tissue. Emphysema, pulmonary inflammation and atherosclerosis were assessed in the chronic study.In the acute study, intranasal LPS administration induced a marked systemic IL-6 response on day 3, which was inhibited after MSC treatment. Furthermore, MSC treatment reduced LPS-induced total cell count in BAL due to reduced neutrophil numbers. In the chronic study, LPS increased emphysema but did not aggravate atherosclerosis. Emphysema and atherosclerosis development were unaffected after MSC treatment.These data show that MSC inhibit LPS-induced pulmonary and systemic inflammation in the acute study, whereas MSC treatment had no effect on inflammation, emphysema and atherosclerosis development in the chronic study.

  14. Acute and chronic effects of treatment with mesenchymal stromal cells on LPS-induced pulmonary inflammation, emphysema and atherosclerosis development.

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    Khedoe, P Padmini S J; de Kleijn, Stan; van Oeveren-Rietdijk, Annemarie M; Plomp, Jaap J; de Boer, Hetty C; van Pel, Melissa; Rensen, Patrick C N; Berbée, Jimmy F P; Hiemstra, Pieter S

    2017-01-01

    COPD is a pulmonary disorder often accompanied by cardiovascular disease (CVD), and current treatment of this comorbidity is suboptimal. Systemic inflammation in COPD triggered by smoke and microbial exposure is suggested to link COPD and CVD. Mesenchymal stromal cells (MSC) possess anti-inflammatory capacities and MSC treatment is considered an attractive treatment option for various chronic inflammatory diseases. Therefore, we investigated the immunomodulatory properties of MSC in an acute and chronic model of lipopolysaccharide (LPS)-induced inflammation, emphysema and atherosclerosis development in APOE*3-Leiden (E3L) mice. Hyperlipidemic E3L mice were intranasally instilled with 10 μg LPS or vehicle twice in an acute 4-day study, or twice weekly during 20 weeks Western-type diet feeding in a chronic study. Mice received 0.5x106 MSC or vehicle intravenously twice after the first LPS instillation (acute study) or in week 14, 16, 18 and 20 (chronic study). Inflammatory parameters were measured in bronchoalveolar lavage (BAL) and lung tissue. Emphysema, pulmonary inflammation and atherosclerosis were assessed in the chronic study. In the acute study, intranasal LPS administration induced a marked systemic IL-6 response on day 3, which was inhibited after MSC treatment. Furthermore, MSC treatment reduced LPS-induced total cell count in BAL due to reduced neutrophil numbers. In the chronic study, LPS increased emphysema but did not aggravate atherosclerosis. Emphysema and atherosclerosis development were unaffected after MSC treatment. These data show that MSC inhibit LPS-induced pulmonary and systemic inflammation in the acute study, whereas MSC treatment had no effect on inflammation, emphysema and atherosclerosis development in the chronic study.

  15. Skin condition and its relationship to systemic inflammation in chronic obstructive pulmonary disease

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    Majewski S

    2017-08-01

    Full Text Available Sebastian Majewski,1,2 Anna Pietrzak,3 Damian Tworek,4 Karolina Szewczyk,5 Anna Kumor-Kisielewska,1 Zofia Kurmanowska,5 Paweł Górski,1,2 Anna Zalewska-Janowska,3,* Wojciech Jerzy Piotrowski1,2,* 1Department of Pneumology and Allergy, Medical University of Lodz, Lodz, Poland; 2Healthy Ageing Research Centre (HARC, Lodz, Poland; 3Department of Psychodermatology, Medical University of Lodz, Lodz, Poland; 4Department of General and Oncological Pulmonology, Medical University of Lodz, Lodz, Poland; 5Department of Molecular Bases of Medicine, Medical University of Lodz, Lodz, Poland *These authors contributed equally to this work Background: The systemic (extrapulmonary effects and comorbidities of chronic obstructive pulmonary disease (COPD contribute substantially to its burden. The supposed link between COPD and its systemic effects on distal organs could be due to the low-grade systemic inflammation. The aim of this study was to investigate whether the systemic inflammation may influence the skin condition in COPD patients. Materials and methods: Forty patients with confirmed diagnosis of COPD and a control group consisting of 30 healthy smokers and 20 healthy never-smokers were studied. Transepidermal water loss, stratum corneum hydration, skin sebum content, melanin index, erythema index, and skin temperature were measured with worldwide-acknowledged biophysical measuring methods at the volar forearm of all participants using a multifunctional skin physiology monitor. Biomarkers of systemic inflammation, including high-sensitivity C-reactive protein (hsCRP, interleukin-6 (IL-6, and tumor necrosis factor α (TNF-α, were measured in serum using commercially available enzyme-linked immunosorbent assays. Results: There were significant differences between COPD patients and healthy never-smokers in skin temperature, melanin index, sebum content, and hydration level (P<0.05, but not for transepidermal water loss and erythema index. No significant

  16. Mechanisms of microglial activation in models of inflammation and hypoxia: Implications for chronic intermittent hypoxia.

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    Kiernan, Elizabeth A; Smith, Stephanie M C; Mitchell, Gordon S; Watters, Jyoti J

    2016-03-15

    Chronic intermittent hypoxia (CIH) is a hallmark of sleep apnoea, a condition associated with diverse clinical disorders. CIH and sleep apnoea are characterized by increased reactive oxygen species formation, peripheral and CNS inflammation, neuronal death and neurocognitive deficits. Few studies have examined the role of microglia, the resident CNS immune cells, in models of CIH. Thus, little is known concerning their direct contributions to neuropathology or the cellular mechanisms regulating their activities during or following pathological CIH. In this review, we identify gaps in knowledge regarding CIH-induced microglial activation, and propose mechanisms based on data from related models of hypoxia and/or hypoxia-reoxygenation. CIH may directly affect microglia, or may have indirect effects via the periphery or other CNS cells. Peripheral inflammation may indirectly activate microglia via entry of pro-inflammatory molecules into the CNS, and/or activation of vagal afferents that trigger CNS inflammation. CIH-induced release of damage-associated molecular patterns from injured CNS cells may also activate microglia via interactions with pattern recognition receptors expressed on microglia. For example, Toll-like receptors activate mitogen-activated protein kinase/transcription factor pathways required for microglial inflammatory gene expression. Although epigenetic effects from CIH have not yet been studied in microglia, potential epigenetic mechanisms in microglial regulation are discussed, including microRNAs, histone modifications and DNA methylation. Epigenetic effects can occur during CIH, or long after it has ended. A better understanding of CIH effects on microglial activities may be important to reverse CIH-induced neuropathology in patients with sleep disordered breathing. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

  17. Chronic urticaria in patients with autoimmune thyroiditis: Significance of severity of thyroid gland inflammation

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    Mustafa Gulec

    2011-01-01

    Full Text Available Background: There is a clear association between autoimmune thyroiditis (AT and chronic urticaria/angioedema (CUA. However, not all patients with AT demonstrate urticaria. Aims: The aim of the study was to investigate in which patients with AT did CUA become a problem. A sensitive inflammation marker, neopterine (NP was used to confirm whether the severity of inflammation in the thyroid gland was responsible for urticaria or not. Methods: Neopterine levels were assessed in patients with AT with urticaria and without urticaria. Furthermore, levels were compared in relation to pre and post levothyroxine treatment. Twenty-seven patients with urticaria (Group 1 and 28 patients without urticaria (Group 2 were enrolled in the study. A course of levothyroxine treatment was given to all patients, and urine neopterine levels before and after the trial were obtained. Results: All patients completed the trial. Mean age in Group 1 and Group 2 was similar (35.70 ± 10.86 years and 38.36 ± 10.38 years, respectively (P=0.358. Pre-treatment urine neopterine levels were significantly higher in Group 1 (P=0.012. Post-treatment levels decreased in each group, as expected. However, the decrease in the neopterine level was insignificant in the patients of Group 2 (P=0.282. In Group 1, a significant decrease in post-treatment neopterine levels (P=0.015 was associated with the remission of urticaria. Conclusion: In patients with CUA and AT, pre-treatment elevated levels of NP, and its decrease with levothyroxine treatment along with symptomatic relief in urticaria, may be evidence of the relationship between the degree of inflammation in thyroid and presence of urticaria.

  18. Is Chronic Inflammation a Possible Cause of Obesity-Related Depression?

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    Magdalena Olszanecka-Glinianowicz

    2009-01-01

    Full Text Available Adult obesity has been associated with depression, especially in women. Whether depression leads to obesity or obesity causes depression is unclear. Chronic inflammation is observed in obesity and depression. In 63 obese women without additional diseases depression level was assessed with the Beck's questionnaire. After evaluation of depression level study group was divided into groups according to the mood status (A—without depression, B—mild depression, and C—severe depression, and serum concentration of TNF-α, sTNFs, leptin, and IL-6 were measured by ELISA. No differences in age, body mass, BMI, and body composition were observed in study groups. We did not observe differences of serum concentrations of TNF-α, sTNFRs, leptin, and IL-6 between subgroup A and subgroups B and C. It seems that circulating adipokines did not exert influence on depression levels in obese women.

  19. Mediators of Inflammation and Angiogenesis in Chronic Spontaneous Urticaria: Are They Potential Biomarkers of the Disease?

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    Ilaria Puxeddu

    2017-01-01

    Full Text Available In chronic spontaneous urticaria (CSU, different pathophysiological mechanisms, potentially responsible for the development of the disease, have been recently described. It is likely that the activation of skin mast cells with consequent release of histamine and other proinflammatory mediators is responsible for vasodilation in the lesional skin of CSU. However, the underlying causes of mast cell activation in the disease are largely unknown and remain to be identified. Thus, in this review, we discuss new insights in the pathogenesis of CSU, focusing on inflammation and angiogenesis. The understanding of these mechanisms will enable the identification of biomarkers useful for the diagnosis, follow-up, and management of CSU and will allow the development of novel, more specific, and patient-tailored therapies.

  20. [Understanding and treatment strategy of the pathogenesis of periodontal disease based on chronic inflammation].

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    Murakami, Tomohiko

    2016-05-01

    Prolonged inflammation continuously promotes the infiltration of macrophages in the organization and chronically induces the production of pro-inflammatory cytokines such as TNF and IL-1. In periodontal tissues, these inflammatory cytokines enhance the differentiation and activity of osteoclasts, which cause destruction of the alveolar bone. Therefore, inhibition of inflammatory cytokine production leads to the prevention or treatment of periodontal disease. IL-1 is a pro-inflammatory cytokine that strongly enhances the bone-resorbing activity of osteoclasts. Elucidation of mechanisms for the production of IL-1 is critical for understanding the pathogenesis of periodontal disease. This paper reviews recent findings of the molecular mechanisms regulating IL-1 production and focuses on inflammasome.

  1. Does gamma-aminobutyric acid (GABA influence the development of chronic inflammation in rheumatoid arthritis?

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    Bridges S Louis

    2008-01-01

    Full Text Available Abstract Background Recent studies have demonstrated a role for spinal p38 MAP kinase (MAPK in the development of chronic inflammation and peripheral arthritis and a role for GABA in the inhibition of p38 MAPK mediated effects. Integrating these data suggests that GABA may play a role in downregulating mechanisms that lead to the production of proinflammatory agents such as interleukin-1, interleukin-6, and matrix metalloproteinase 3 – agents implicated in the pathogenesis of rheumatoid arthritis (RA. Genetic studies have also associated RA with members of the p38 MAPK pathway. Hypothesis We propose a hypothesis for an inefficient GABA signaling system that results in unchecked proinflammatory cytokine production via the p38 MAPK pathway. This model also supports the need for increasing research in the integration of immunology and neuroscience.

  2. Small molecule therapeutics for inflammation-associated chronic musculoskeletal degenerative diseases: Past, present and future.

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    Chen, Yangwu; Huang, Jiayun; Tang, Chenqi; Chen, Xiao; Yin, Zi; Heng, Boon Chin; Chen, Weishan; Shen, Weiliang

    2017-10-01

    Inflammation-associated chronic musculoskeletal degenerative diseases (ICMDDs) like osteoarthritis and tendinopathy often results in morbidity and disability, with consequent heavy socio-economic burden. Current available therapies such as NSAIDs and glucocorticoid are palliative rather than disease-modifying. Insufficient systematic research data on disease molecular mechanism also makes it difficult to exploit valid therapeutic targets. Small molecules are designed to act on specific signaling pathways and/or mechanisms of cellular physiology and function, and have gradually shown potential for treating ICMDDs. In this review, we would examine and analyze recent developments in small molecule drugs for ICMDDs, suggest possible feasible improvements in treatment modalities, and discuss future research directions. Copyright © 2017. Published by Elsevier Inc.

  3. Elevated [11C]-D-deprenyl uptake in chronic Whiplash Associated Disorder suggests persistent musculoskeletal inflammation.

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    Clas Linnman

    Full Text Available There are few diagnostic tools for chronic musculoskeletal pain as structural imaging methods seldom reveal pathological alterations. This is especially true for Whiplash Associated Disorder, for which physical signs of persistent injuries to the neck have yet to be established. Here, we sought to visualize inflammatory processes in the neck region by means Positron Emission Tomography using the tracer (11C-D-deprenyl, a potential marker for inflammation. Twenty-two patients with enduring pain after a rear impact car accident (Whiplash Associated Disorder grade II and 14 healthy controls were investigated. Patients displayed significantly elevated tracer uptake in the neck, particularly in regions around the spineous process of the second cervical vertebra. This suggests that whiplash patients have signs of local persistent peripheral tissue inflammation, which may potentially serve as a diagnostic biomarker. The present investigation demonstrates that painful processes in the periphery can be objectively visualized and quantified with PET and that (11C-D-deprenyl is a promising tracer for these purposes.

  4. A Potential Role for Acrolein in Neutrophil-Mediated Chronic Inflammation.

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    Noerager, Brett D; Xu, Xin; Davis, Virginia A; Jones, Caleb W; Okafor, Svetlana; Whitehead, Alicia; Blalock, J Edwin; Jackson, Patricia L

    2015-12-01

    Neutrophils (PMNs) are key mediators of inflammatory processes throughout the body. In this study, we investigated the role of acrolein, a highly reactive aldehyde that is ubiquitously present in the environment and produced endogenously at sites of inflammation, in mediating PMN-mediated degradation of collagen facilitating proline-glycine-proline (PGP) production. We treated peripheral blood neutrophils with acrolein and analyzed cell supernatants and lysates for matrix metalloproteinase-9 (MMP-9) and prolyl endopeptidase (PE), assessed their ability to break down collagen and release PGP, and assayed for the presence of leukotriene A4 hydrolase (LTA4H) and its ability to degrade PGP. Acrolein treatment induced elevated production and functionality of collagen-degrading enzymes and generation of PGP fragments. Meanwhile, LTA4H levels and triaminopeptidase activity declined with increasing concentrations of acrolein thereby sparing PGP from enzymatic destruction. These findings suggest that acrolein exacerbates the acute inflammatory response mediated by neutrophils and sets the stage for chronic pulmonary and systemic inflammation.

  5. Inhibition of G0/G1 Switch 2 Ameliorates Renal Inflammation in Chronic Kidney Disease

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    Naoya Matsunaga

    2016-11-01

    Full Text Available Chronic kidney disease (CKD is a global health problem, and novel therapies to treat CKD are urgently needed. Here, we show that inhibition of G0/G1 switch 2 (G0s2 ameliorates renal inflammation in a mouse model of CKD. Renal expression of chemokine (C-C motif ligand 2 (Ccl2 was increased in response to p65 activation in the kidneys of wild-type 5/6 nephrectomy (5/6Nx mice. Moreover, 5/6Nx Clk/Clk mice, which carry homozygous mutations in the gene encoding circadian locomotor output cycles kaput (CLOCK, did not exhibit aggravation of apoptosis or induction of F4/80-positive cells. The renal expression of G0s2 in wild-type 5/6Nx mice was important for the transactivation of Ccl2 by p65. These pathologies were ameliorated by G0s2 knockdown. Furthermore, a novel small-molecule inhibitor of G0s2 expression was identified by high-throughput chemical screening, and the inhibitor suppressed renal inflammation in 5/6Nx mice. These findings indicated that G0s2 inhibitors may have applications in the treatment of CKD.

  6. Chronic Inflammation and Neutrophil Activation as Possible Causes of Joint Diseases in Ballet Dancers

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    Leandro da Silva Borges

    2014-01-01

    Full Text Available Herein, we investigated the effects of a ballet class on the kinetic profiles of creatine kinase (CK and lactate dehydrogenase (LDH activities, cytokines, complement component 3 (C3, and the concentrations of immunoglobulin (Ig, IgA and IgM, in ballerinas. We also verified neutrophil death and ROS release. Blood samples were taken from 13 dancers before, immediately after, and 18 hours after a ballet class. The ballet class increased the plasma activities of CK-total (2.0-fold immediately after class, while the activities of CK-cardiac muscle (1.0-fold and LDH (3.0-fold were observed to increase 18 hours after the class. Levels of the TNF-α, IL-1β, IgG, and IgA were not affected under the study conditions. The exercise was found to induce neutrophil apoptosis (6.0-fold 18 hours after the ballet class. Additionally, immediately after the ballet class, the neutrophils from the ballerinas were found to be less responsive to PMA stimulus. Conclusion. Ballet class was found to result in inflammation in dancers. The inflammation caused by the ballet class remained for 18 hours after the exercise. These findings are important in preventing the development of chronic lesions that are commonly observed in dancers, such as those with arthritis and synovitis.

  7. Chronic inflammation and neutrophil activation as possible causes of joint diseases in ballet dancers.

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    Borges, Leandro da Silva; Bortolon, José Ricardo; Santos, Vinicius Coneglian; de Moura, Nivaldo Ribeiro; Dermargos, Alexandre; Cury-Boaventura, Maria Fernanda; Gorjão, Renata; Pithon-Curi, Tania Cristina; Hatanaka, Elaine

    2014-01-01

    Herein, we investigated the effects of a ballet class on the kinetic profiles of creatine kinase (CK) and lactate dehydrogenase (LDH) activities, cytokines, complement component 3 (C3), and the concentrations of immunoglobulin (Ig), IgA and IgM, in ballerinas. We also verified neutrophil death and ROS release. Blood samples were taken from 13 dancers before, immediately after, and 18 hours after a ballet class. The ballet class increased the plasma activities of CK-total (2.0-fold) immediately after class, while the activities of CK-cardiac muscle (1.0-fold) and LDH (3.0-fold) were observed to increase 18 hours after the class. Levels of the TNF-α , IL-1β, IgG, and IgA were not affected under the study conditions. The exercise was found to induce neutrophil apoptosis (6.0-fold) 18 hours after the ballet class. Additionally, immediately after the ballet class, the neutrophils from the ballerinas were found to be less responsive to PMA stimulus. Ballet class was found to result in inflammation in dancers. The inflammation caused by the ballet class remained for 18 hours after the exercise. These findings are important in preventing the development of chronic lesions that are commonly observed in dancers, such as those with arthritis and synovitis.

  8. Lung inflammation biomarkers and lung function in children chronically exposed to arsenic

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    Olivas-Calderón, Edgar, E-mail: edgar_olivascalderon@hotmail.com [Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila (Mexico); School of Medicine, University Juarez of Durango, Gomez Palacio, Durango (Mexico); Recio-Vega, Rogelio, E-mail: rrecio@yahoo.com [Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila (Mexico); Gandolfi, A. Jay, E-mail: gandolfi@pharmacy.arizona.edu [Southwest Environmental Health Science Center, University of Arizona, Tucson, AZ (United States); Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ (United States); Lantz, R. Clark, E-mail: lantz@email.arizona.edu [Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ (United States); Department of Pharmacology and Toxicology, University of Arizona, Tucson, AZ (United States); González-Cortes, Tania, E-mail: taniagc2201@hotmail.com [Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila (Mexico); Gonzalez-De Alba, Cesar, E-mail: cesargonzalezalba@hotmail.com [Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila (Mexico); Froines, John R., E-mail: jfroines@ucla.edu [Center for Environmental and Occupational Health, School of Public Health, University of California at Los Angeles, Los Angeles, CA (United States); Espinosa-Fematt, Jorge A., E-mail: dr.jorge.espinosa@gmail.com [School of Medicine, University Juarez of Durango, Gomez Palacio, Durango (Mexico)

    2015-09-01

    Evidence suggests that exposure to arsenic in drinking water during early childhood or in utero has been associated with an increase in respiratory symptoms or diseases in the adulthood, however only a few studies have been carried out during those sensitive windows of exposure. Recently our group demonstrated that the exposure to arsenic during early childhood or in utero in children was associated with impairment in the lung function and suggested that this adverse effect could be due to a chronic inflammation response to the metalloid. Therefore, we designed this cross-sectional study in a cohort of children associating lung inflammatory biomarkers and lung function with urinary As levels. A total of 275 healthy children were partitioned into four study groups according with their arsenic urinary levels. Inflammation biomarkers were measured in sputum by ELISA and the lung function was evaluated by spirometry. Fifty eight percent of the studied children were found to have a restrictive spirometric pattern. In the two highest exposed groups, the soluble receptor for advanced glycation end products' (sRAGE) sputum level was significantly lower and matrix metalloproteinase-9 (MMP-9) concentration was higher. When the biomarkers were correlated to the urinary arsenic species, negative associations were found between dimethylarsinic (DMA), monomethylarsonic percentage (%MMA) and dimethylarsinic percentage (%DMA) with sRAGE and positive associations between %DMA with MMP-9 and with the MMP-9/tissue inhibitor of metalloproteinase (TIMP-1) ratio. In conclusion, chronic arsenic exposure of children negatively correlates with sRAGE, and positively correlated with MMP-9 and MMP-9/TIMP-1 levels, and increases the frequency of an abnormal spirometric pattern. Arsenic-induced alterations in inflammatory biomarkers may contribute to the development of restrictive lung diseases. - Highlights: • First study in children evaluating lung inflammatory biomarkers and As levels

  9. The role of CXC chemokines in the transition of chronic inflammation to esophageal and gastric cancer.

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    Verbeke, Hannelien; Hannelien, Verbeke; Geboes, Karel; Karel, Geboes; Van Damme, Jo; Jo, Van Damme; Struyf, Sofie; Sofie, Struyf

    2012-01-01

    Chronic inflammation may increase the risk to develop cancer, for instance esophagitis or gastritis may lead to development of esophageal or gastric cancer, respectively. The key molecules attracting leukocytes to local inflammatory sites are chemokines. We here provide a systematic review on the impact of CXC chemokines (binding the receptors CXCR1, CXCR2, CXCR3 and CXCR4) on the transition of chronic inflammation in the upper gastrointestinal tract to neoplasia. CXCR2 ligands, including GRO-α,β,γ/CXCL1,2,3, ENA-78/CXCL5 and IL-8/CXCL8 chemoattract pro-tumoral neutrophils. In addition, angiogenic CXCR2 ligands stimulate the formation of new blood vessels, facilitating tumor progression. The CXCR4 ligand SDF-1/CXCL12 also promotes tumor development by stimulating angiogenesis and by favoring metastasis of CXCR4-positive tumor cells to distant organs producing SDF-1/CXCL12. Furthermore, these angiogenic chemokines also directly enhance tumor cell survival and proliferation. In contrast, the CXCR3 ligands Mig/CXCL9, IP-10/CXCL10 and I-TAC/CXCL11 are angiostatic and attract anti-tumoral T lymphocytes and may therefore mediate tumor growth retardation and regression. Thus, chemokines exert diverging, sometimes dual roles in tumor biology as described for esophageal and gastric cancer. Therefore extensive research is needed to completely unravel the complex chemokine code in specific cancers. Possibly, chemokine-targeted cancer therapy will have to be adapted to the individual's chemokine profile. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. [Cardiac markers in different degrees of chronic kidney disease: influence of inflammation and previous heart disease].

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    Quiroga, Borja; Goicoechea, Marian; García de Vinuesa, Soledad; Verde, Eduardo; Verdalles, Ursula; Yuste, Claudia; Reque, Javier; Luño, José

    2012-06-30

    Troponin T (TnT), brain natriuretic peptide (BNP) and its precursor (NT-proBNP) are useful markers of acute coronary events and heart failure. The aim of this study was to analyze the influence of chronic renal failure, inflammation and heart disease in these biomarkers. In 266 patients with different stages of chronic renal diseases, the following parameters were measured: cardiac markers (TnT, BNP and NT-proBNP), renal function, inflammatory markers (hsCRP, fibrinogen, albumin, uric acid and white blood cells). We recorded the cardiovascular history. Ventricular dysfunction and left ventricular hypertrophy were assessed by echocardiography. A significant correlation between cardiac markers and inflammatory parameters such as fibrinogen, hsCRP and albumin was found. Age (OR 1.05, P = .021), serum albumin (OR: 0.06, P=.006), ischemic heart disease (OR: 8.17, P=.0092) and renal failure (OR: 1.67, P=.05) were predictors of higher BNP levels. Age (OR 1.05, P=.0097), serum albumin (OR: 0.12, P=.001), ischemic heart disease (OR: 3.43, P=.034), renal failure (OR: 1, 65, P=.036) and heart failure (OR: 4.33, P=.0312) were predictors of elevated NT-proBNP. Previous ischemic heart disease alone increased TnT levels (OR: 6.51, P=.0012). Age, previous cardiac disease and inflammation increase cardiac marker levels in patients with different stages of renal disease, but the degree of renal failure is an important factor influencing NT-proBNP levels. However, ischemic heart disease alone increases the levels of TnT. Copyright © 2011 Elsevier España, S.L. All rights reserved.

  11. Regulatory effects of zinc on cadmium-induced cytotoxicity in chronic inflammation.

    Directory of Open Access Journals (Sweden)

    Paola Bonaventura

    Full Text Available Zinc (Zn has major effects on immune system activation while Cadmium (Cd has anti-inflammatory and anti-proliferative effects in several chronic inflammatory contexts. The aim of this work was to investigate by which mechanisms Zn could compete with Cd and eventually counteract its deleterious effects. Rheumatoid arthritis (RA synoviocytes exposed to cytokines were used as a model of chronic inflammation; osteoarthritis (OA synoviocytes were used as control.Cell/medium fractionation constants were analyzed for different metals by inductively-coupled-plasma mass-spectrometry by comparison to the 70Zn spike. Interleukin-17 (IL-17 and tumor necrosis factor-alpha (TNF-α were used to mimic inflammation. Gene expression of ZIP-8 importer, metallothioneins-1 (MT-1s and the ratio between metalloprotease-3 and the tissue inhibitor of metalloproteinases (MMP-3/TIMP-1 were evaluated after pre-exposure to cytokines and Cd, with or without the addition of exogenous Zn (0.9 ppm. Cell viability was measured by neutral red assay and IL-6 production by ELISA.Synoviocytes selectively absorbed and retained Cd in comparison to Zn. Metal import increased with IL-17/TNF-α exposure, through the enhanced ZIP-8 expression. Zn did not modify ZIP-8 expression, while Cd reduced it (p<0.05. Zn induced a reduction of Cd-induced MT-1s expression, in particular of MT-1X (3-fold, and subsequently the final intra-cellular content of Cd. By reducing Cd accumulation in cells, Zn reversed Cd anti-proliferative and anti-inflammatory effects but preserved the low MMP-3/TIMP-1 ratio induced by Cd, which was enhanced by inflammatory conditions.Zinc counteracts the deleterious effect of Cd by reducing its import and accumulation in the cell, without the reactivation of destructive pathways such as MMPs.

  12. Comparative experimental evaluation of the efficacy of Prostamol Uno and Samprost on rat model of chronic aseptic prostate inflammation.

    Science.gov (United States)

    Pahomova, A V; Borovskaja, T G; Fomina, T I; Ermolaeva, L A; Vychuzhanina, A V; Rumpel, O A; Granstrem, O K; Baranova, O V

    2011-11-01

    Comparative experimental evaluation of the efficiency of prostatotropic drugs Prostamol Uno and Samprost on the model of the chronic aseptic prostate inflammation in rats was performed. It was established that peptide drug Samprost decelerates sclerotic processes in the prostate gland to a greater extent than herbal preparation Prostamol Uno. Both products equally stimulate secretory activity of the gland. Prostamol Uno, unlike Samprost, prevents the development of reduced sexual motivation, one of the complications of chronic prostatitis.

  13. Relative contribution of health-related behaviours and chronic diseases to the socioeconomic patterning of low-grade inflammation.

    Science.gov (United States)

    Bonaccio, Marialaura; Di Castelnuovo, Augusto; Pounis, George; De Curtis, Amalia; Costanzo, Simona; Persichillo, Mariarosaria; Cerletti, Chiara; Donati, Maria Benedetta; de Gaetano, Giovanni; Iacoviello, Licia

    2017-06-01

    To test the association of low-grade inflammation with socioeconomic status (SES) and determine the relative contribution of prevalent chronic diseases and health-related behaviours in explaining such association. Cross-sectional analysis on 19,867 subjects (age ≥35, 48.1% men) recruited within the Moli-sani study from 2005 to 2010 (Italy). A score of low-grade inflammation, including platelet and leukocyte counts, the granulocyte-to-lymphocyte ratio, and C-reactive protein was applied. SES was measured by education, household income, and occupational social class. Low SES was associated with elevated levels of low-grade inflammation. Health behaviours (including adiposity, smoking, physical activity, and Mediterranean diet adherence) explained 53.5, 53.9, and 84.9% of the association between social class, income, and education with low-grade inflammation, respectively. Adiposity and body mass index showed a prominent role, while prevalent chronic diseases and conditions only marginally attenuated SES inequalities in inflammation. Low-grade inflammation was socioeconomically patterned in a large Mediterranean population. Potentially modifiable behavioural factors explained the greatest part of this association with a leading contribution of adiposity, body mass index, and physical activity.

  14. Expression of eicosanoid receptors subtypes and eosinophilic inflammation: implication on chronic rhinosinusitis

    Directory of Open Access Journals (Sweden)

    Van Cauwenberge Paul

    2006-05-01

    Full Text Available Abstract Background Eicosanoid receptors are G-protein-coupled receptors playing an important immunomodulatory role in airway diseases. However, there is little information on the expression of these receptors and their link with eosinophilic inflammation in paranasal sinus diseases. We aimed with this study to investigate the tissue expression of leukotrienes and prostaglandin E2 receptors in chronic rhinosinusitis patients and the link of this regulation with eosinophilic inflammation. Methods Samples were prepared from nasal tissue of patients with chronic rhinosinusitis without nasal polyps (CRS, n = 11, with nasal polyps (CRS-NP, n = 13 and healthy subjects (Controls, n = 6. mRNA expression of CysLT1, CysLT2, BLT1, BLT2, E-prostanoid receptors (EP1, EP2, EP3, EP4 and sol-IL-5Rα was determined by real-time PCR. Concentrations of PGE2, LTC4/D4/E4, LTB4 and sol-IL-5Rα were determined by ELISA and of ECP by ImmunoCap. Protein expression and tissue localization of eicosanoid receptors and activated eosinophils were evaluated by immunohistochemistry. Results CysLT1 mRNA expression was significantly increased in CRS-NP compared to CRS and controls, and CRS compared to controls, whereas CysLT2 mRNA was enhanced in both CRS groups without differences between them. Levels of both receptors correlated to the number of activated eosinophils, sol-IL-5Rα, ECP and LTC4/D4/E4 concentrations in the disease groups. PGE2 protein concentrations and prostanoid receptors EP1 and EP3 were down-regulated in the CRS-NP tissue vs. CRS and controls, whereas EP2 and EP4 expression was enhanced in CRS and CRS-NP patients vs. controls. No differences in BLT receptors were observed between patients and controls. Conclusion CyLTs receptors are up-regulated in nasal polyp tissue and their expression correlate with eosinophilic inflammation supporting previous results. Eicosanoid receptors mRNA pattern observed suggests that down-regulation of EP1 and EP3 in CRS-NP and

  15. Poorly Understood Aspects of Striated Muscle Contraction

    Directory of Open Access Journals (Sweden)

    Alf Månsson

    2015-01-01

    Full Text Available Muscle contraction results from cyclic interactions between the contractile proteins myosin and actin, driven by the turnover of adenosine triphosphate (ATP. Despite intense studies, several molecular events in the contraction process are poorly understood, including the relationship between force-generation and phosphate-release in the ATP-turnover. Different aspects of the force-generating transition are reflected in the changes in tension development by muscle cells, myofibrils and single molecules upon changes in temperature, altered phosphate concentration, or length perturbations. It has been notoriously difficult to explain all these events within a given theoretical framework and to unequivocally correlate observed events with the atomic structures of the myosin motor. Other incompletely understood issues include the role of the two heads of myosin II and structural changes in the actin filaments as well as the importance of the three-dimensional order. We here review these issues in relation to controversies regarding basic physiological properties of striated muscle. We also briefly consider actomyosin mutation effects in cardiac and skeletal muscle function and the possibility to treat these defects by drugs.

  16. High intensity interval training favourably affects antioxidant and inflammation mRNA expression in early-stage chronic kidney disease.

    Science.gov (United States)

    Tucker, Patrick S; Briskey, David R; Scanlan, Aaron T; Coombes, Jeff S; Dalbo, Vincent J

    2015-12-01

    Increased levels of oxidative stress and inflammation have been linked to the progression of chronic kidney disease. To reduce oxidative stress and inflammation related to chronic kidney disease, chronic aerobic exercise is often recommended. Data suggests high intensity interval training may be more beneficial than traditional aerobic exercise. However, appraisals of differing modes of exercise, along with explanations of mechanisms responsible for observed effects, are lacking. This study assessed effects of eight weeks of high intensity interval training (85% VO2max), versus low intensity exercise (45-50% VO2max) and sedentary behaviour, in an animal model of early-stage chronic kidney disease. We examined kidney-specific mRNA expression of genes related to endogenous antioxidant enzyme activity (glutathione peroxidase 1; Gpx1, superoxide dismutase 1; Sod1, and catalase; Cat) and inflammation (kidney injury molecule 1; Kim1 and tumour necrosis factor receptor super family 1b; Tnfrsf1b), as well as plasma F2-isoprostanes, a marker of lipid peroxidation. Compared to sedentary behaviour, high intensity interval training resulted in increased mRNA expression of Sod1 (p=0.01) and Cat (pinterval training resulted in increased mRNA expression of Cat (pinterval training was superior to sedentary behaviour and low intensity exercise as high intensity interval training beneficially influenced expression of genes related to endogenous antioxidant enzyme activity and inflammation. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Protective actions of green tea polyphenols and alfacalcidol on bone microstructure in female rats with chronic inflammation

    Science.gov (United States)

    This study investigated the effects of green tea polyphenols (GTP) and alfacalcidol on bone microstructure and strength along with possible mechanisms in rats with chronic inflammation. A 12-week study using a 2 (no GTP vs. 0.5%, w/v GTP in drinking water) × 2 (no alfacalcidol vs. 0.05 ug/kg alfacal...

  18. Green tea polyphenols mitigate bone loss of female rats in a chronic inflammation-induced bone loss model

    Science.gov (United States)

    The purpose of this study was to explore bioavailability, efficacy, and molecular mechanisms of green tea polyphenols (GTP) related to preventing bone loss in rats with chronic inflammation. A 2 (placebo vs. lipopolysaccharide, LPS) × 2 (no GTP vs. 0.5% GTP in drinking water) factorial design using ...

  19. The role of chronic inflammation in the development of gastrointestinal cancers: reviewing cancer prevention with natural anti-inflammatory intervention.

    Science.gov (United States)

    Lee, Ho-Jae; Park, Jong-Min; Han, Young Min; Gil, Hong Kwon; Kim, Jinhyung; Chang, Ji Young; Jeong, Migyeong; Go, Eun-Jin; Hahm, Ki Baik

    2016-01-01

    Inflammatory mediators alter the local environment of tumors, known as the tumor microenvironment. Mechanistically, chronic inflammation induces DNA damage, but understanding this hazard may help in the search for new chemopreventive agents for gastrointestinal (GI) cancer which attenuate inflammation. In the clinic, GI cancer still remains a major cause of cancer-associated mortality, chemoprevention with anti-inflammatory agents is thought to be a realistic approach to reduce GI cancer. Proton pump inhibitors, monoclonal antibodies targeting tumor necrosis factor-alpha, anti-sense targeted smad7 and non-steroidal anti-inflammatory agents have been investigated for their potential to prevent inflammation-based GI cancer. Besides these, a wide variety of natural products have also shown potential for the prevention of GI cancer. In this review, the authors will provide insights to explain the mechanistic connection between inflammation and GI cancer, as well as describe a feasible cancer prevention strategy based on anti-inflammatory treatments.

  20. Signatures of reproductive events on blood counts and biomarkers of inflammation: Implications for chronic disease risk.

    Directory of Open Access Journals (Sweden)

    Daniel W Cramer

    Full Text Available Whether inflammation mediates how reproductive events affect chronic-disease risk is unclear. We studied inflammatory biomarkers in the context of reproductive events using National Health and Nutrition Examination Survey (NHANES data. From 15,986 eligible women from the 1999-2011 data cycles, we accessed information on reproductive events, blood counts, C-reactive protein (CRP, and total homocysteine (tHCY. We calculated blood-count ratios including: platelet-lymphocyte (PLR, lymphocyte-monocyte (LMR, platelet-monocyte (PMR, and neutrophil-monocyte (NMR. Using sampling weights per NHANES guidelines, means for counts, ratios, or biomarkers by reproductive events were compared using linear regression. We performed trend tests and calculated p-values with partial sum of squares F-tests. Higher PLR and lower LMR were associated with nulliparity. In postmenopausal women, lower PMR was associated with early age at first birth and higher NMR with later age at and shorter interval since last birth. Lower PNR and higher neutrophils and tHCY were associated with early natural menopause. In all women, the neutrophil count correlated positively with CRP; but, in premenopausal women, correlated inversely with tHCY. Reproductive events leave residual signatures on blood counts and inflammatory biomarkers that could underlie their links to chronic disease risk.

  1. Correlation of alkaline phosphatase activity to clinical parameters of inflammation in smokers suffering from chronic periodontitis

    Directory of Open Access Journals (Sweden)

    Vishakha Grover

    2016-01-01

    Full Text Available Context: Current clinical periodontal diagnostic techniques emphasize the assessment of clinical and radiographic signs of periodontal diseases which can provide a measure of history of disease. Hence, new methodologies for early identification and determination of periodontal disease activity need to be explored which will eventually result in expedited treatment. Aim: To evaluate the correlation of alkaline phosphatase (ALP activity in gingival crevicular fluid (GCF to clinical parameters of periodontal inflammation in smokers with chronic periodontitis. Materials and Methods: Study population included 15 smoker male patients in the age group of 35–55 years suffering from moderate generalized chronic periodontitis with history of smoking present. Following parameters were evaluated at baseline, 1 month and 3 months after scaling and root planing: plaque index, bleeding index, probing pocket depth (PD, relative attachment level (RAL, and GCF ALP activity. Statistical Analysis Used: Independent variables for measurements over time were analyzed by using Wilcoxon signed rank test. Results: A statistically significant reduction in all the clinical parameters and GCF ALP activity was observed from baseline to 1 month and 3 months. A correlation was observed between change in GCF ALP activity and PD reduction as well as gain in RAL at 3 months. Conclusion: The present study emphasizes that total ALP activity could be used as a marker for periodontal disease activity in smokers. Estimation of changes in the levels of this enzyme has a potential to aid in the detection of progression of periodontal disease and monitoring the response to periodontal therapy.

  2. Chikungunya Arthritis: Implications of Acute and Chronic Inflammation Mechanisms on Disease Management.

    Science.gov (United States)

    Zaid, Ali; Gérardin, Patrick; Taylor, Adam; Mostafavi, Helen; Malvy, Denis; Mahalingam, Suresh

    2018-04-01

    In the past decade, arboviruses-arthropod-borne viruses-have been the focus of public health institutions worldwide following a spate of devastating outbreaks. Chikungunya virus, an arbovirus that belongs to the alphavirus genus, is a reemerging arthritogenic virus that has caused explosive outbreaks since 2006, notably on Réunion Island, and more recently in the Caribbean, South America, India, and Southeast Asia. The severity of arthritic disease caused by chikungunya virus has prompted public health authorities in affected countries to develop specific guidelines to tackle this pathogen. Chikungunya virus disease manifests first as an acute stage of severe joint inflammation and febrile illness, which later progresses to a chronic stage, during which patients may experience debilitating and persisting articular pain for extended periods. This review aims to provide a broad perspective on current knowledge of chikungunya virus pathogenesis by identifying key clinical and experimental studies that have contributed to our understanding of chikungunya virus to date. In addition, the review explores the practical aspects of treatment and management of both acute and chronic chikungunya virus based on clinical experience during chikungunya virus outbreaks. Finally, recent findings on potential therapeutic solutions-from antiviral agents to immunomodulators-are reviewed to provide both viral immunologists and clinical rheumatologists with a balanced perspective on the nature of a reemerging arboviral disease of significant public health concern, and insight into future therapeutic approaches to better address the treatment and management of chikungunya virus. © 2017, American College of Rheumatology.

  3. The Prevalence of Oral Inflammation Among Denture Wearing Patients with Chronic Obstructive Pulmonary Disease.

    Science.gov (United States)

    Przybyłowska, D; Rubinsztajn, R; Chazan, R; Swoboda-Kopeć, E; Kostrzewa-Janicka, J; Mierzwińska-Nastalska, E

    2015-01-01

    Oral inflammation is an important contributor to the etiology of chronic obstructive pulmonary disease, which can impact patient's health status. Previous studies indicate that people with poor oral health are at higher risk for nosocomial pneumonia. Denture wearing is one promoting factor in the development of mucosal infections. Colonization of the denture plaque by Gram-negative bacteria, Candida spp., or other respiratory pathogens, occurring locally, may be aspirated to the lungs. The studies showed that chronic obstructive pulmonary disease (COPD) patients treated with combinations of medicines with corticosteroids more frequently suffer from Candida-associated denture stomatitis. Treatment of oral candidiasis in patients with COPD constitutes a therapeutic problem. Therefore, it is essential to pay attention to the condition of oral mucosal membrane and denture hygiene habits. The guidelines for care and maintenance of dentures for COPD patients are presented in this paper. The majority of patients required improvement of their prosthetic and oral hygiene. Standard oral hygiene procedures in relation to dentures, conducted for prophylaxis of stomatitis complicated by mucosal infection among immunocompromised patients, are essential to maintain healthy oral tissues. The elimination of traumatic denture action in dental office, compliance with oral and denture hygiene, proper use and storage of prosthetic appliances in a dry environment outside the oral cavity can reduce susceptibility to infection. Proper attention to hygiene, including brushing and rinsing the mouth, may also help prevent denture stomatitis in these patients.

  4. Excess ω-6 fatty acids influx in aging drives metabolic dysregulation, electrocardiographic alterations, and low-grade chronic inflammation.

    Science.gov (United States)

    Kain, Vasundhara; Ingle, Kevin A; Kachman, Maureen; Baum, Heidi; Shanmugam, Gobinath; Rajasekaran, Namakkal S; Young, Martin E; Halade, Ganesh V

    2018-02-01

    Maintaining a balance of ω-6 and ω-3 fatty acids is essential for cardiac health. Current ω-6 and ω-3 fatty acids in the American diet have shifted from the ideal ratio of 2:1 to almost 20:1; while there is a body of evidence that suggests the negative impact of such a shift in younger organisms, the underlying age-related metabolic signaling in response to the excess influx of ω-6 fatty acids is incompletely understood. In the present study, young (6 mo old) and aging (≥18 mo old) mice were fed for 2 mo with a ω-6-enriched diet. Excess intake of ω-6 enrichment decreased the total lean mass and increased nighttime carbohydrate utilization, with higher levels of cardiac cytokines indicating low-grade chronic inflammation. Dobutamine-induced stress tests displayed an increase in PR interval, a sign of an atrioventricular defect in ω-6-fed aging mice. Excess ω-6 fatty acid intake in aging mice showed decreased 12-lipoxygenase with a concomitant increase in 15-lipoxygenase levels, resulting in the generation of 15( S)-hydroxyeicosatetraenoic acid, whereas cyclooxygenase-1 and -2 generated prostaglandin E 2 , leukotriene B 4, and thromboxane B 2 . Furthermore, excessive ω-6 fatty acids led to dysregulated nuclear erythroid 2-related factor 2/antioxidant-responsive element in aging mice. Moreover, ω-6 fatty acid-mediated changes were profound in aging mice with respect to the eicosanoid profile while minimal changes were observed in the size and shape of cardiomyocytes. These findings provide compelling evidence that surplus consumption of ω-6 fatty acids, coupled with insufficient intake of ω-3 fatty acids, is linked to abnormal changes in ECG. These manifestations contribute to functional deficiencies and expansion of the inflammatory mediator milieu during later stages of aging. NEW & NOTEWORTHY Aging has a profound impact on the metabolism of fatty acids to maintain heart function. The excess influx of ω-6 fatty acids in aging perturbed

  5. Occurrence of hypermutable Pseudomonas aeruginosa in cystic fibrosis patients is associated with the oxidative stress caused by chronic lung inflammation

    DEFF Research Database (Denmark)

    Ciofu, Oana; Riis, Bente; Pressler, Tacjana

    2005-01-01

    .4% of the CF patients. The earliest mutator P. aeruginosa isolates were found after 5 years from the onset of the chronic lung infection, and once they were present in the CF lung, the prevalence increased with time. The hypermutable isolates were significantly more resistant to antipseudomonal antibiotics......Oxidative stress caused by chronic lung inflammation in patients with cystic fibrosis (CF) and chronic lung infection with Pseudomonas aeruginosa is characterized by the reactive oxygen species (ROS) liberated by polymorphonuclear leukocytes (PMNs). We formulated the hypothesis that oxidation...

  6. Nutrition disorder and systemic inflammation in patients with chronic obstructive pulmonary disease.

    Science.gov (United States)

    Cirić, Zorica; Stanković, Ivana; Pejčić, Tatjana; Ristić, Lidija; Rančić, Milan; Radović, Milan; Nastasijević-Borovec, Desa

    2013-08-01

    To detect nutrition disorders (underweight and obesity) in patients with chronic obstructive disease (COPD) and presence of systemic inflammation by determination of inflammatory mediators serum values C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α) and leptin. The examination involved 85 patients with COPD. Nutrition categories were defined by body mass index (BMI). Fat free mass (FFM) was evaluated by mid upper-arm circumference (MUAC) and fat mass (FM) by tricipital skin-fold thickness (TFS). Values of TNF-α and leptin were measured by standardized ELISA kits and, CRP by latex turbidimetry. There were 14 (16.5%) underweight patients, 28 (32.9%) normal, 28 (32.9%) pre-obese and 15 (17.6%) obese. Values of MUAC and TSF were significantly different among the nutrition categories (p=0.000). The lowest MUAC and TSF values were in the underweight, and the highest in the obese. There was no significant difference of CRP and TNF-α among nutrition categories. Leptin of the underweight and normal nutrition was significantly different from leptin of the pre-obese and obese (p=0.000). The highest CRP and the lowest TNF-α and leptin were in the underweight patients. The obese had the lowest CRP (although increased as compared to normal values) and the highest leptin, while the pre-obese had the highest TNF-α. Two basic nutrition disorders (underweight and obesity) were manifested in COPD patients. The inflammatory profile differs between underweight COPD patients and obese. Probably that happens due to systemic inflammation, and in part due to dysfunction of adipose tissue.

  7. Metabolic Syndrome as a Factor Affecting Systemic Inflammation in Patients with Chronic Obstructive Pulmonary Disease.

    Science.gov (United States)

    Rubinsztajn, R; Przybyłowski, T; Maskey-Warzęchowska, M; Paplińska-Goryca, M; Nejman-Gryz, P; Karwat, K; Chazan, R

    2017-01-01

    Chronic obstructive pulmonary disease (COPD) is a systemic disease which may be associated with other comorbidities. The aim of the study was to estimate the incidence of metabolic syndrome (MS) in COPD patients and to assess its impact on systemic inflammation and lung function. MS was diagnosed in accordance with the recommendations of the Polish Forum for the Prevention of Cardiovascular Diseases. The study group consisted of 267 patients with stable COPD in all stages of severity. All patients underwent spirometry with bronchial reversibility testing and 6 min walk test (6MWT). The following blood tests were evaluated: lipid profile, glucose and C-reactive protein as well as serum concentration of IL-6, leptin, adiponectin, and endothelin. MS was diagnosed in 93 patients (35.8%). No differences were observed in the incidence of MS in relation to airflow limitation severity (mild; moderate; severe and very severe: 38.9; 36.3; 35.2 and 25.0%, respectively). FEV 1 (% predicted), FVC (% predicted), 6MWT distance (6MWD), age, and the number of pack-years were similar in patients with and without MS. MS was more frequent in males than females (38.7 vs. 28.4%, p > 0.05). Serum concentrations of IL-6, endothelin, leptin, and CRP were higher in the MS group, contrary to adiponectin concentration which was lower (p < 0.01). MS was more frequent in male COPD patients, but there were no differences in its frequency between patients with different severity of airflow limitation. We conclude that MS, as a comorbidity, occurs in all COPD stages and affects systemic inflammation. MS incidence does not depend on COPD severity.

  8. A gut microbiota-targeted dietary intervention for amelioration of chronic inflammation underlying metabolic syndrome.

    Science.gov (United States)

    Xiao, Shuiming; Fei, Na; Pang, Xiaoyan; Shen, Jian; Wang, Linghua; Zhang, Baorang; Zhang, Menghui; Zhang, Xiaojun; Zhang, Chenhong; Li, Min; Sun, Lifeng; Xue, Zhengsheng; Wang, Jingjing; Feng, Jie; Yan, Feiyan; Zhao, Naisi; Liu, Jiaqi; Long, Wenmin; Zhao, Liping

    2014-02-01

    Chronic inflammation induced by endotoxin from a dysbiotic gut microbiota contributes to the development of obesity-related metabolic disorders. Modification of gut microbiota by a diet to balance its composition becomes a promising strategy to help manage obesity. A dietary scheme based on whole grains, traditional Chinese medicinal foods, and prebiotics (WTP diet) was designed to meet human nutritional needs as well as balance the gut microbiota. Ninety-three of 123 central obese volunteers (BMI ≥ 28 kg m(-2) ) completed a self-controlled clinical trial consisting of 9-week intervention on WTP diet followed by a 14-week maintenance period. The average weight loss reached 5.79 ± 4.64 kg (6.62 ± 4.94%), in addition to improvement in insulin sensitivity, lipid profiles, and blood pressure. Pyrosequencing of fecal samples showed that phylotypes related to endotoxin-producing opportunistic pathogens of Enterobacteriaceae and Desulfovibrionaceae were reduced significantly, while those related to gut barrier-protecting bacteria of Bifidobacteriaceae increased. Gut permeability, measured as lactulose/mannitol ratio, was decreased compared with the baseline. Plasma endotoxin load as lipopolysaccharide-binding protein was also significantly reduced, with concomitant decrease in tumor necrosis factor-α, interleukin-6, and an increase in adiponectin. These results suggest that modulation of the gut microbiota via dietary intervention may enhance the intestinal barrier integrity, reduce circulating antigen load, and ultimately ameliorate the inflammation and metabolic phenotypes. © 2013 The Authors. FEMS Microbiology Ecology pubished by John Wiley & Sons Ltd on behalf of the Federation of European Microbiological Societies.

  9. The relation of hepcidin to iron disorders, inflammation and hemoglobin in chronic kidney disease.

    Directory of Open Access Journals (Sweden)

    Lucile Mercadal

    Full Text Available The metabolism of hepcidin is profoundly modified in chronic kidney disease (CKD. We investigated its relation to iron disorders, inflammation and hemoglobin (Hb level in 199 non-dialyzed, non-transplanted patients with CKD stages 1-5. All had their glomerular filtration rate measured by 51Cr-EDTA renal clearance (mGFR, as well as measurements of iron markers including hepcidin and of erythropoietin (EPO. Hepcidin varied from 0.2 to 193 ng/mL. The median increased from 23.3 ng/mL [8.8-28.7] to 36.1 ng/mL [14.1-92.3] when mGFR decreased from ≥60 to <15 mL/min/1.73 m2 (p = 0.02. Patients with absolute iron deficiency (transferrin saturation (TSAT <20% and ferritin <40 ng/mL had the lowest hepcidin levels (5.0 ng/mL [0.7-11.7], and those with a normal iron profile (TSAT ≥20% and ferritin ≥40, the highest (34.5 ng/mL [23.7-51.6]. In multivariate analysis, absolute iron deficiency was associated with lower hepcidin values, and inflammation combined with a normal or functional iron profile with higher values, independent of other determinants of hepcidin concentration, including EPO, mGFR, and albuminemia. The hepcidin level, although it rose overall when mGFR declined, collapsed in patients with absolute iron deficiency. There was a significant interaction with iron status in the association between Hb and hepcidin. Except in absolute iron deficiency, hepcidin's negative association with Hb level indicates that it is not down-regulated in CKD anemia.

  10. Proteinuria: an ignored marker of inflammation and cardiovascular disease in chronic hemodialysis

    Directory of Open Access Journals (Sweden)

    Trimarchi H

    2011-12-01

    Full Text Available Hernán Trimarchi1, Alexis Muryan2, Mariana Dicugno2, Pablo Young3, Mariano Forrester1, Fernando Lombi1, Vanesa Pomeranz1, Romina Iriarte1, María Soledad Raña1, Mirta Alonso21Nephrology, 2Biochemistry, 3Internal Medicine Services, Hospital Británico de Buenos Aires, ArgentinaBackground: Cardiovascular disease is the leading cause of morbidity and mortality in hemodialysis (HD patients, the main etiologies being diabetes and hypertension. Cardiac and inflammatory biomarkers are usually employed to assess risk or damage, or during follow-up. Proteinuria is considered a strong predictor of morbidity, a cause of inflammation, oxidative stress, hemodynamic alteration, and progression of chronic kidney disease. However, proteinuria is rarely considered in the clinical assessment of HD patients.Methods: This was a concurrent, cohort-observational, cross-sectional study in which 52 chronic HD subjects were divided into three groups according to the degree of proteinuria: Group (G A: <1 g/day, n = 25; GB: 1–3 g/day, n = 13; GC: >3 g/day, n = 14. Baseline hemoglobin, albuminemia, cholesterol, body mass index, Malnutrition-Inflammatory Score, pro-B-type natriuretic peptide, troponin T, C-reactive protein (CRP, and ultrafiltration rates were analyzed.Results: There was no difference between groups in terms of baseline age, gender, hypertension, cause of renal failure, hemoglobin, cholesterol, albumin, CRP levels, cardiac biomarkers, adiponectin, body mass index, or Malnutrition-Inflammatory Score. Time on HD: GA, 34.56 ± 23.3 (range [r]: 6–88; GB, 25.15 ± 19.40 (r: 6–58; GC, 18.21 ± 9.58 (r: 6–74 months; P = 0.048. Proteinuria: GA, 0.33 ± 0.30 (r: 0.0–0.88; GB, 1.66 ± 0.54 (r: 1.03–2.75; GC, 7.18 ± 2.80 (r: 3.04–21.5 g/day; P < 0.001. Mean ultrafiltration rates were significantly different: GA, 2.80 ± 0.73; GB: 1.85 ± 0.96 liters/session; P = 0.003. Fourteen diabetic patients were identified (27%: GA, 3 (12%; GB, 3 (23%; GC, 8 (57

  11. Longitudinal study of a mouse model of chronic pulmonary inflammation using breath hold gated micro-CT

    International Nuclear Information System (INIS)

    Artaechevarria, Xabier; Perez-Martin, Daniel; Munoz-Barrutia, Arrate; Ortiz-de-Solorzano, Carlos; Blanco, David; Biurrun, Gabriel de; Montuenga, Luis M.; Torres, Juan P. de; Zulueta, Javier J.; Bastarrika, Gorka

    2010-01-01

    To evaluate the feasibility of using automatic quantitative analysis of breath hold gated micro-CT images to detect and monitor disease in a mouse model of chronic pulmonary inflammation, and to compare image-based measurements with pulmonary function tests and histomorphometry. Forty-nine A/J mice were used, divided into control and inflammation groups. Chronic inflammation was induced by silica aspiration. Fourteen animals were imaged at baseline, and 4, 14, and 34 weeks after silica aspiration, using micro-CT synchronized with ventilator-induced breath holds. Lung input impedance was measured as well using forced oscillation techniques. Five additional animals from each group were killed after micro-CT for comparison with histomorphometry. At all time points, micro-CT measurements show statistically significant differences between the two groups, while first differences in functional test parameters appear at 14 weeks. Micro-CT measurements correlate well with histomorphometry and discriminate diseased and healthy groups better than functional tests. Longitudinal studies using breath hold gated micro-CT are feasible on the silica-induced model of chronic pulmonary inflammation, and automatic measurements from micro-CT images correlate well with histomorphometry, being more sensitive than functional tests to detect lung damage in this model. (orig.)

  12. Longitudinal study of a mouse model of chronic pulmonary inflammation using breath hold gated micro-CT

    Energy Technology Data Exchange (ETDEWEB)

    Artaechevarria, Xabier; Perez-Martin, Daniel; Munoz-Barrutia, Arrate; Ortiz-de-Solorzano, Carlos [Center for Applied Medical Research, University of Navarra, Cancer Imaging Laboratory, Oncology Division, Pamplona (Spain); Blanco, David; Biurrun, Gabriel de; Montuenga, Luis M. [Center for Applied Medical Research, University of Navarra, Biomarkers Laboratory, Pamplona (Spain); Torres, Juan P. de; Zulueta, Javier J. [Clinica Universidad de Navarra, Pneumology Department, Pamplona (Spain); Bastarrika, Gorka [Clinica Universidad de Navarra, Radiology Department, Pamplona (Spain)

    2010-11-15

    To evaluate the feasibility of using automatic quantitative analysis of breath hold gated micro-CT images to detect and monitor disease in a mouse model of chronic pulmonary inflammation, and to compare image-based measurements with pulmonary function tests and histomorphometry. Forty-nine A/J mice were used, divided into control and inflammation groups. Chronic inflammation was induced by silica aspiration. Fourteen animals were imaged at baseline, and 4, 14, and 34 weeks after silica aspiration, using micro-CT synchronized with ventilator-induced breath holds. Lung input impedance was measured as well using forced oscillation techniques. Five additional animals from each group were killed after micro-CT for comparison with histomorphometry. At all time points, micro-CT measurements show statistically significant differences between the two groups, while first differences in functional test parameters appear at 14 weeks. Micro-CT measurements correlate well with histomorphometry and discriminate diseased and healthy groups better than functional tests. Longitudinal studies using breath hold gated micro-CT are feasible on the silica-induced model of chronic pulmonary inflammation, and automatic measurements from micro-CT images correlate well with histomorphometry, being more sensitive than functional tests to detect lung damage in this model. (orig.)

  13. Increased serum inflammatory markers in the absence of clinical and skeletal muscle inflammation in patients with chronic obstructive pulmonary disease.

    Science.gov (United States)

    Piehl-Aulin, Karin; Jones, Ian; Lindvall, Björn; Magnuson, Anders; Abdel-Halim, Samy M

    2009-01-01

    Muscle wasting and cachexia are common occurrences in patients with chronic obstructive pulmonary disease (COPD). The current study aimed to investigate markers of inflammation in the circulation and skeletal muscle that might be associated with development of muscle wasting. Three groups of patients with mild, moderate and severe COPD and matched healthy controls were recruited. Serum levels of C-reactive protein (CRP), high-sensitivity CRP (hs-CRP), IL-6, IL-8, TNF-alpha, cortisol, insulin-like growth factor 1 (IGF-1), leptin and ghrelin were analysed. Skeletal muscle inflammation was investigated microscopically using a panel of antibodies and standard staining for inflammatory cell infiltration. All COPD patients were clinically stable, with no sign of inflammation and normal CRP values. Compared to controls, significantly increased hs-CRP levels were observed in all COPD patient groups. Significant rises in IL-6 levels were first observed in moderate COPD, while IL-8 levels were significantly elevated at the late severe stage. Circulating levels of TNF-alpha, cortisol, IGF-1, leptin and ghrelin were similar to control levels. No microscopic signs of skeletal muscle inflammation were observed. Our results identify hs-CRP as an early marker of inflammation that is significantly increased in the circulation even in mild COPD. Serum interleukin levels appear to be increased with disease progress. These changes were manifested in the absence of any clinical signs of disease exacerbation, evidence of skeletal muscle inflammation or hormonal changes.

  14. Chronic immune activation and inflammation in the pathogenesis of AIDS and cancer.

    Science.gov (United States)

    Dalgleish, Angus G; O'Byrne, Ken J

    2002-01-01

    Infection with the human immunodeficiency virus (HIV) invariably leads to the development of acquired immunodeficiency syndrome (AIDS) in most infected humans, yet does so rarely, if at all, in HIV-infected chimpanzees. The differences between the two species are not due to differences in cellular receptors or an inability of the chimpanzee to be infected, but rather to the lack of pan-immune activation in the infected primate. This results in reduced apoptotic death in CD4+ T-helper lymphocytes and a lower viral load. In humans the degree of chronic immune activation correlates with virus load and clinical outcome with high immune activation leading to high viral loads and the more rapid progression to AIDS and death. The type of immune perturbation seen in HIV-associated AIDS is similar to that of chronic graft-versus-host disease (GVHD) where reduced cell-mediated immune (CMI) responses occur early in the course of the disease and where humoral responses (HI) predominate. A reduced CMI response occurs in a number of chronic infectious diseases, including tuberculosis and leishmaniasis. More recently, it has become increasingly apparent that the CMI response is suppressed in virtually all malignant diseases, including melanoma and colorectal and prostate cancer. This raises the possibility that, as the malignant process develops, the cancer cells evolve to subvert the CMI response. Moreover, the reduced CMI response seen in colorectal cancer (CRC) patients is completely reversed following curative surgery strongly supporting the hypothesis that CRC can suppress the systemic immune response. Wound healing, ovulation, embryo implantation, and fetal growth are all associated with suppressed CMI and neovascularization (the formation of new blood vessels) or angiogenesis (the formation of new blood vessels from an existing vasculature). If unresolved, wound healing results in chronic inflammation, which can give rise to the phenomenon of "scar cancers." Indeed all the

  15. Development and validation of an animal model of prostate inflammation-induced chronic pelvic pain: evaluating from inflammation of the prostate to pain behavioral modifications.

    Directory of Open Access Journals (Sweden)

    Feng Zeng

    Full Text Available BACKGROUND: Chronic prostatitis/Chronic pelvic pain syndrome (CP/CPPS is the most common type of prostatitis. Due to the lack of a suitable animal model partly, the pathogenesis for this condition is obscure. In the current study we developed and validated an animal model for nonbacterial prostatitis and prostate inflammation-induced chronic pelvic pain in rats with the use of intraprostatic injection of λ-carrageenan. METHODS: Male Sprague-Dawley rats weighing 250-350 g were used for the experiments. After intraprostatic injection of 3% λ-carrageenan, at different time points(after 24 h, 7 d, 14 d and 30 d of injection, radiant heat and von Frey filaments were applied to the scrotum of rats to measure the heat and mechanical thresholds respectively. Then the prostate was removed for histology, and cyclooxygenase (COX 2 protein expression was determined by Western-blot. Evans blue(50 mg/kg was also injected intravenously to assess for plasma protein extravasation at different time points after injection of λ-carrageenan. RESULTS: Compared to control group, inflamed animals showed a significant reduction in mechanical threshold (mechanical allodynia at 24 h and 7d(p = 0.022,0.046, respectively, and a significant reduction in heat threshold (thermal hyperalgesia at 24 h, 7d and 14 d(p = 0.014, 0.018, 0.002, respectively in the scrotal skin. Significant increase of inflammatory cell accumulation, COX2 expression and Evans blue extravasation were observed at 24 h, 7d and 14 d after injection. CONCLUSIONS: Intraprostatic λ-carrageenan injection induced neurogenic prostatitis and prostate inflammation pain, which lasted at least 2 weeks. The current model is expected to be a valuable preclinical tool to study the neurobiological mechanisms of male chronic pelvic pain.

  16. Neural plasticity in the gastrointestinal tract: chronic inflammation, neurotrophic signals, and hypersensitivity.

    Science.gov (United States)

    Demir, Ihsan Ekin; Schäfer, Karl-Herbert; Tieftrunk, Elke; Friess, Helmut; Ceyhan, Güralp O

    2013-04-01

    Neural plasticity is not only the adaptive response of the central nervous system to learning, structural damage or sensory deprivation, but also an increasingly recognized common feature of the gastrointestinal (GI) nervous system during pathological states. Indeed, nearly all chronic GI disorders exhibit a disease-stage-dependent, structural and functional neuroplasticity. At structural level, GI neuroplasticity usually comprises local tissue hyperinnervation (neural sprouting, neural, and ganglionic hypertrophy) next to hypoinnervated areas, a switch in the neurochemical (neurotransmitter/neuropeptide) code toward preferential expression of neuropeptides which are frequently present in nociceptive neurons (e.g., substance P/SP, calcitonin-gene-related-peptide/CGRP) and of ion channels (TRPV1, TRPA1, PAR2), and concomitant activation of peripheral neural glia. The functional counterpart of these structural alterations is altered neuronal electric activity, leading to organ dysfunction (e.g., impaired motility and secretion), together with reduced sensory thresholds, resulting in hypersensitivity and pain. The present review underlines that neural plasticity in all GI organs, starting from esophagus, stomach, small and large intestine to liver, gallbladder, and pancreas, actually exhibits common phenotypes and mechanisms. Careful appraisal of these GI neuroplastic alterations reveals that--no matter which etiology, i.e., inflammatory, infectious, neoplastic/malignant, or degenerative--neural plasticity in the GI tract primarily occurs in the presence of chronic tissue- and neuro-inflammation. It seems that studying the abundant trophic and activating signals which are generated during this neuro-immune-crosstalk represents the key to understand the remarkable neuroplasticity of the GI tract.

  17. Metabolically induced liver inflammation leads to NASH and differs from LPS- or IL-1 beta-induced chronic inflammation

    NARCIS (Netherlands)

    Liang, Wen; Lindeman, Jan H.; Menke, Aswin L.; Koonen, Debby P.; Morrison, Martine; Havekes, Louis M.; van den Hoek, Anita M.; Kleemann, Robert

    The nature of the chronic inflammatory component that drives the development of non-alcoholic steatohepatitis (NASH) is unclear and possible inflammatory triggers have not been investigated systematically. We examined the effect of non-metabolic triggers (lipopolysaccharide (LPS), interleukin-1 beta

  18. Metabolically induced liver inflammation leads to NASH and differs from LPS-or IL-1β-induced chronic inflammation

    NARCIS (Netherlands)

    Liang, W.; Lindeman, J.H.; Menke, A.L.; Koonen, D.P.; Morrison, M.; Havekes, L.M.; Hoek, A.M. van den; Kleemann, R.

    2014-01-01

    The nature of the chronic inflammatory component that drives the development of non-alcoholic steatohepatitis (NASH) is unclear and possible inflammatory triggers have not been investigated systematically. We examined the effect of non-metabolic triggers (lipopolysaccharide (LPS), interleukin-1β

  19. Hyperglycemia Aggravates Hepatic Ischemia Reperfusion Injury by Inducing Chronic Oxidative Stress and Inflammation

    Directory of Open Access Journals (Sweden)

    Yihan Zhang

    2016-01-01

    Full Text Available Aim. To investigate whether hyperglycemia will aggravate hepatic ischemia reperfusion injury (HIRI and the underlying mechanisms. Methods. Control and streptozotocin-induced diabetic Sprague-Dawley rats were subjected to partial hepatic ischemia reperfusion. Liver histology, transferase, inflammatory cytokines, and oxidative stress were assessed accordingly. Similarly, BRL-3A hepatocytes were subjected to hypoxia/reoxygenation (H/R after high (25 mM or low (5.5 mM glucose culture. Cell viability, reactive oxygen species (ROS, and activation of nuclear factor-erythroid 2-related factor 2 (Nrf2 and nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB were determined. Results. Compared with control, diabetic rats presented more severe hepatic injury and increased hepatic inflammatory cytokines and oxidative stress. HIRI in diabetic rats could be ameliorated by pretreatment of N-acetyl-L-cysteine (NAC or apocynin. Excessive ROS generation and consequent Nrf2 and NF-κB translocation were determined after high glucose exposure. NF-κB translocation and its downstream cytokines were further increased in high glucose cultured group after H/R. While proper regulation of Nrf2 to its downstream antioxidases was observed in low glucose cultured group, no further induction of Nrf2 pathway by H/R after high glucose culture was identified. Conclusion. Hyperglycemia aggravates HIRI, which might be attributed to chronic oxidative stress and inflammation and potential malfunction of antioxidative system.

  20. Biochemical and molecular mechanisms for the association between obesity, chronic inflammation, and breast cancer.

    Science.gov (United States)

    Rose, David P; Vona-Davis, Linda

    2014-01-01

    Upper body obesity is a risk factor for postmenopausal breast cancer and is related to an aggressive tumor phenotype and a poor prognosis regardless of menopausal status. After the menopause, the major mechanism for the association with disease risk is elevated estrogen production by adipose tissue, due to a high level of aromatase activity: these hormone-dependent tumors express both estrogen and progesterone receptors. Other important biological factors of risk include leptin and adiponectin, adipokines with opposing endocrine and paracrine activities, and obesity-related hyperinsulinemia. Chronic inflammation of the breast adipose tissue, which occurs in some obese women and is indicated by the accumulation of macrophages around dead adipocytes ("crown-like structures"), rather than adiposity per se, may prove to be the pathological lesion responsible for both local aromatase induction, and enhanced invasiveness and metastatic capacity through biological mechanisms that involve leptin, tumor necrosis factor-α, and insulin. A causal association between obesity in premenopausal women and breast cell epithelial-mesenchymal transition, perhaps with the participation of the Wnt signaling pathway, and aggressive hormone-independent breast cancer is suggested by a number of experimental and clinical studies. © 2013 International Union of Biochemistry and Molecular Biology.

  1. Intravesical Dimethyl Sulfoxide Inhibits Acute and Chronic Bladder Inflammation in Transgenic Experimental Autoimmune Cystitis Models

    Directory of Open Access Journals (Sweden)

    Ronald Kim

    2011-01-01

    Full Text Available New animal models are greatly needed in interstitial cystitis/painful bladder syndrome (IC/PBS research. We recently developed a novel transgenic cystitis model (URO-OVA mice that mimics certain key aspects of IC/PBS pathophysiology. This paper aimed to determine whether URO-OVA cystitis model was responsive to intravesical dimethyl sulfoxide (DMSO and if so identify the mechanisms of DMSO action. URO-OVA mice developed acute cystitis upon adoptive transfer of OVA-specific OT-I splenocytes. Compared to PBS-treated bladders, the bladders treated with 50% DMSO exhibited markedly reduced bladder histopathology and expression of various inflammatory factor mRNAs. Intravesical DMSO treatment also effectively inhibited bladder inflammation in a spontaneous chronic cystitis model (URO-OVA/OT-I mice. Studies further revealed that DMSO could impair effector T cells in a dose-dependent manner in vitro. Taken together, our results suggest that intravesical DMSO improves the bladder histopathology of IC/PBS patients because of its ability to interfere with multiple inflammatory and bladder cell types.

  2. Chronic infection with Helicobacter pylori does not provoke major systemic inflammation in healthy adults

    DEFF Research Database (Denmark)

    Brenner, H; Berg, Gabriele; Fröhlich, M

    1999-01-01

    It has been suggested that chronic infection with Helicobacter pylori (H. pylori), in particular infection with virulent strains producing the cytotoxin-associated protein CagA, may increase the risk of coronary heart disease by generation of a persistent low-grade inflammatory stimulus. We...... assessed the relation between serological markers of H. pylori infection and various markers of systemic inflammation in a population-based sample of 1834 men and women aged 18-88. A total of 39.3% of the sample had a positive IgG response, and among these a slight majority was CagA positive. Infection...... with H. pylori was unrelated to C-reactive protein and the leukocyte count, regardless of CagA status. There was an inverse relation between H. pylori infection and serum albumin. The adjusted OR (95% CI) of an albumin level in the bottom versus the top third were 2.2 (1.5-3.1) and 2.0 (1...

  3. Contribution of defective PS recognition and efferocytosis to chronic inflammation and autoimmunity

    Directory of Open Access Journals (Sweden)

    Stanley Gititu Kimani

    2014-11-01

    Full Text Available Rapid and efficient clearance of apoptotic cells results in elimination of auto-antigens and provides a strong anti-inflammatory and immunosuppressive signal to prevent autoimmunity. While professional and non-professional phagocytes utilize a wide array of surface receptors to recognize apoptotic cells, recognition of phosphatidylserine (PS on apoptotic cells by PS receptors on phagocytes is emblematic signal for efferocytosis in metazoans. PS-dependent efferocytosis is associated with production of anti-inflammatory factors such as IL-10 and TGF-β that function, in part, to maintain tolerance to auto-antigens. In contrast, when apoptotic cells fail to be recognized and processed for degradation, auto-antigens persist, which can trigger immune activation leading to autoantibody production and autoimmunity. Despite the fact that genetic mouse models clearly demonstrate that loss of PS receptors can lead to age-dependent autoimmune diseases reminiscent of systemic lupus erythematosus (SLE, link between PS and defective clearance in chronic inflammation and human autoimmunity is not well delineated. In this hypothesis and theory, we review emerging questions developing in the field that may be of relevance to SLE and human autoimmunity.

  4. Microbiota alterations in acute and chronic gastrointestinal inflammation of cats and dogs

    Science.gov (United States)

    Honneffer, Julia B; Minamoto, Yasushi; Suchodolski, Jan S

    2014-01-01

    The intestinal microbiota is the collection of the living microorganisms (bacteria, fungi, protozoa, and viruses) inhabiting the gastrointestinal tract. Novel bacterial identification approaches have revealed that the gastrointestinal microbiota of dogs and cats is, similarly to humans, a highly complex ecosystem. Studies in dogs and cats have demonstrated that acute and chronic gastrointestinal diseases, including inflammatory bowel disease (IBD), are associated with alterations in the small intestinal and fecal microbial communities. Of interest is that these alterations are generally similar to the dysbiosis observed in humans with IBD or animal models of intestinal inflammation, suggesting that microbial responses to inflammatory conditions of the gut are conserved across mammalian host types. Studies have also revealed possible underlying susceptibilities in the innate immune system of dogs and cats with IBD, which further demonstrate the intricate relationship between gut microbiota and host health. Commonly identified microbiome changes in IBD are decreases in bacterial groups within the phyla Firmicutes and Bacteroidetes, and increases within Proteobacteia. Furthermore, a reduction in the diversity of Clostridium clusters XIVa and IV (i.e., Lachnospiraceae and Clostridium coccoides subgroups) are associated with IBD, suggesting that these bacterial groups may play an important role in maintenance of gastrointestinal health. Future studies are warranted to evaluate the functional changes associated with intestinal dysbiosis in dogs and cats. PMID:25469017

  5. Hepcidin-dependent and hepcidin-independent regulation of erythropoiesis in a mouse model of anemia of chronic inflammation.

    Science.gov (United States)

    Langdon, Jacqueline M; Yates, Saiah C; Femnou, Laurette K; McCranor, Bryan J; Cheadle, Chris; Xue, Qian-Li; Vaulont, Sophie; Civin, Curt I; Walston, Jeremy D; Roy, Cindy N

    2014-05-01

    Increased hepcidin antimicrobial peptide correlates with hypoferremia and anemia in various disease states, but its requirement for anemia of inflammation has not been adequately demonstrated. Anemia of inflammation is usually described as normocytic and normochromic, while diseases associated with over expression of hepcidin, alone, are often microcytic and hypochromic. These differences in erythrocyte parameters suggest anemia in many inflammatory states may not be fully explained by hepcidin-mediated iron sequestration. We used turpentine-induced sterile abscesses to model chronic inflammation in mice with targeted disruption of Hepcidin 1 [Hepc1 (-/-)] or its positive regulator, Interleukin-6 [IL-6 (-/-)], to determine whether these genes are required for features characteristic of anemia of inflammation. Although hemoglobin levels did not decline in Hepc1 (-/-) mice with sterile abscesses, erythrocyte numbers were significantly reduced compared to untreated Hepc1 (-/-) mice. In contrast, both hemoglobin concentration and erythrocyte number declined significantly in wild type and IL-6 (-/-) mice with sterile abscesses. Both Hepc1 (-/-) and IL-6 (-/-) mice had increased erythrocyte mean cell volume and mean cell hemoglobin following sterile abscesses, while wild types had no change. Thus, IL-6 (-/-) mice with sterile abscesses exhibit an intermediate phenotype between wild type and Hepc1 (-/-). Our results demonstrate the requirement of Hepc1 for the development of anemia in this rodent model. Simultaneously, our results demonstrate hepcidin-independent effects of inflammation on the suppression of erythropoiesis. Our results suggest chronic anemia associated with inflammation may benefit from interventions protecting erythrocyte number in addition to anti-hepcidin interventions aimed at enhancing iron availability. Copyright © 2014 Wiley Periodicals, Inc.

  6. Acute and chronic effects of treatment with mesenchymal stromal cells on LPS-induced pulmonary inflammation, emphysema and atherosclerosis development

    OpenAIRE

    Khedoe, P. Padmini S. J.; de Kleijn, Stan; van Oeveren-Rietdijk, Annemarie M.; Plomp, Jaap J.; de Boer, Hetty C.; van Pel, Melissa; Rensen, Patrick C. N.; Berb?e, Jimmy F. P.; Hiemstra, Pieter S.

    2017-01-01

    Background COPD is a pulmonary disorder often accompanied by cardiovascular disease (CVD), and current treatment of this comorbidity is suboptimal. Systemic inflammation in COPD triggered by smoke and microbial exposure is suggested to link COPD and CVD. Mesenchymal stromal cells (MSC) possess anti-inflammatory capacities and MSC treatment is considered an attractive treatment option for various chronic inflammatory diseases. Therefore, we investigated the immunomodulatory properties of MSC i...

  7. Chronic stress, inflammation, and glucose regulation in U.S. Hispanics from the HCHS/SOL Sociocultural Ancillary Study.

    Science.gov (United States)

    McCurley, Jessica L; Mills, Paul J; Roesch, Scott C; Carnethon, Mercedes; Giacinto, Rebeca E; Isasi, Carmen R; Teng, Yanping; Sotres-Alvarez, Daniela; Llabre, Maria M; Penedo, Frank J; Schneiderman, Neil; Gallo, Linda C

    2015-08-01

    Diabetes prevalence is rising rapidly, and diabetes disproportionately affects Hispanics and other underserved groups. Chronic stress may contribute to diabetes risk, but few studies have examined this relationship in U.S. Hispanics. We examined associations of chronic stress with fasting glucose, glucose tolerance, and glycosylated hemoglobin (HbA1c) in Hispanics without diabetes, and also assessed indirect effects of stress through inflammation (CRP). Participants were 3,923 men and women, aged 18-74, without diabetes, from the four U.S. field centers (Bronx, NY; Chicago, IL; Miami, FL; San Diego, CA) of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) Sociocultural Ancillary study. Participants completed a measure of chronic life stress and a physical exam with oral glucose tolerance test. In a multivariate regression analysis with adjustment for demographic and health covariates, higher chronic stress was related to higher fasting glucose (standardized regression coefficient: β = .09, p stress through inflammation. Findings suggest that higher chronic stress is associated with poorer glucose regulation in Hispanics, prior to the onset of a clinical diabetes diagnosis. © 2015 Society for Psychophysiological Research.

  8. Systemic Inflammation in Chronic Obstructive Pulmonary Disease: May Adipose Tissue Play a Role? Review of the Literature and Future Perspectives

    Directory of Open Access Journals (Sweden)

    Ruzena Tkacova

    2010-01-01

    Full Text Available Chronic obstructive pulmonary disease (COPD is a major cause of morbidity and mortality worldwide. Low-grade systemic inflammation is considered a hallmark of COPD that potentially links COPD to increased rate of systemic manifestations of the disease. Obesity with/without the metabolic syndrome and cachexia represent two poles of metabolic abnormalities that may relate to systemic inflammation. On one hand systemic inflammatory syndrome likely reflects inflammation in the lungs, i.e. results from lung-to plasma spillover of inflammatory mediators. On the other hand, obesity-related hypoxia results in local inflammatory response within adipose tissue per se, and may contribute to elevations in circulatory mediators by spillover from the adipose tissue to the systemic compartment. The extent to which systemic hypoxia contributes to the adipose tissue inflammation remains unknown. We assume that in patients with COPD and concurrent obesity at least three factors play a role in the systemic inflammatory syndrome: the severity of pulmonary impairment, the degree of obesity-related adipose tissue hypoxia, and the severity of systemic hypoxia due to reduced pulmonary functions. The present review summarizes the epidemiological and clinical evidence linking COPD to obesity, the role of adipose tissue as an endocrine organ, and the role of hypoxia in adipose tissue inflammation.

  9. Chronic Sleep Disruption Alters Gut Microbiota, Induces Systemic and Adipose Tissue Inflammation and Insulin Resistance in Mice.

    Science.gov (United States)

    Poroyko, Valeriy A; Carreras, Alba; Khalyfa, Abdelnaby; Khalyfa, Ahamed A; Leone, Vanessa; Peris, Eduard; Almendros, Isaac; Gileles-Hillel, Alex; Qiao, Zhuanhong; Hubert, Nathaniel; Farré, Ramon; Chang, Eugene B; Gozal, David

    2016-10-14

    Chronic sleep fragmentation (SF) commonly occurs in human populations, and although it does not involve circadian shifts or sleep deprivation, it markedly alters feeding behaviors ultimately promoting obesity and insulin resistance. These symptoms are known to be related to the host gut microbiota. Mice were exposed to SF for 4 weeks and then allowed to recover for 2 weeks. Taxonomic profiles of fecal microbiota were obtained prospectively, and conventionalization experiments were performed in germ-free mice. Adipose tissue insulin sensitivity and inflammation, as well as circulating measures of inflammation, were assayed. Effect of fecal water on colonic epithelial permeability was also examined. Chronic SF-induced increased food intake and reversible gut microbiota changes characterized by the preferential growth of highly fermentative members of Lachnospiraceae and Ruminococcaceae and a decrease of Lactobacillaceae families. These lead to systemic and visceral white adipose tissue inflammation in addition to altered insulin sensitivity in mice, most likely via enhanced colonic epithelium barrier disruption. Conventionalization of germ-free mice with SF-derived microbiota confirmed these findings. Thus, SF-induced metabolic alterations may be mediated, in part, by concurrent changes in gut microbiota, thereby opening the way for gut microbiome-targeted therapeutics aimed at reducing the major end-organ morbidities of chronic SF.

  10. Asbestos-Induced Cellular and Molecular Alteration of Immunocompetent Cells and Their Relationship with Chronic Inflammation and Carcinogenesis

    Science.gov (United States)

    Matsuzaki, Hidenori; Maeda, Megumi; Lee, Suni; Nishimura, Yasumitsu; Kumagai-Takei, Naoko; Hayashi, Hiroaki; Yamamoto, Shoko; Hatayama, Tamayo; Kojima, Yoko; Tabata, Rika; Kishimoto, Takumi; Hiratsuka, Junichi; Otsuki, Takemi

    2012-01-01

    Asbestos causes lung fibrosis known as asbestosis as well as cancers such as malignant mesothelioma and lung cancer. Asbestos is a mineral silicate containing iron, magnesium, and calcium with a core of SiO2. The immunological effect of silica, SiO2, involves the dysregulation of autoimmunity because of the complications of autoimmune diseases found in silicosis. Asbestos can therefore cause alteration of immunocompetent cells to result in a decline of tumor immunity. Additionally, due to its physical characteristics, asbestos fibers remain in the lung, regional lymph nodes, and the pleural cavity, particularly at the opening sites of lymphatic vessels. Asbestos can induce chronic inflammation in these areas due to the production of reactive oxygen/nitrogen species. As a consequence, immunocompetent cells can have their cellular and molecular features altered by chronic and recurrent encounters with asbestos fibers, and there may be modification by the surrounding inflammation, all of which eventually lead to decreased tumor immunity. In this paper, the brief results of our investigation regarding reduction of tumor immunity of immunocompetent cells exposed to asbestos in vitro are discussed, as are our findings concerned with an investigation of chronic inflammation and analyses of peripheral blood samples derived from patients with pleural plaque and mesothelioma that have been exposed to asbestos. PMID:22500091

  11. The effect of PPE-induced emphysema and chronic LPS-induced pulmonary inflammation on atherosclerosis development in APOE*3-LEIDEN mice

    NARCIS (Netherlands)

    Khedoe, P.P.S.J.; Wong, M.C.; Wagenaar, G.T.M.; Plomp, J.J.; Eck, M. van; Havekes, L.M.; Rensen, P.C.N.; Hiemstra, P.S.; Berbée, J.F.P.

    2013-01-01

    Background: Chronic obstructive pulmonary disease (COPD) is characterized by pulmonary inflammation, airways obstruction and emphysema, and is a risk factor for cardiovascular disease (CVD). However, the contribution of these individual COPD components to this increased risk is unknown. Therefore,

  12. Pharmacological characterisation of anti-inflammatory compounds in acute and chronic mouse models of cigarette smoke-induced inflammation

    Directory of Open Access Journals (Sweden)

    Mok Joanie

    2010-09-01

    Full Text Available Abstract Background Candidate compounds being developed to treat chronic obstructive pulmonary disease are typically assessed using either acute or chronic mouse smoking models; however, in both systems compounds have almost always been administered prophylactically. Our aim was to determine whether the prophylactic effects of reference anti-inflammatory compounds in acute mouse smoking models reflected their therapeutic effects in (more clinically relevant chronic systems. Methods To do this, we started by examining the type of inflammatory cell infiltrate which occurred after acute (3 days or chronic (12 weeks cigarette smoke exposure (CSE using female, C57BL/6 mice (n = 7-10. To compare the effects of anti-inflammatory compounds in these models, mice were exposed to either 3 days of CSE concomitant with compound dosing or 14 weeks of CSE with dosing beginning after week 12. Budesonide (1 mg kg-1; i.n., q.d., roflumilast (3 mg kg-1; p.o., q.d. and fluvastatin (2 mg kg-1; p.o., b.i.d. were dosed 1 h before (and 5 h after for fluvastatin CSE. These dose levels were selected because they have previously been shown to be efficacious in mouse models of lung inflammation. Bronchoalveolar lavage fluid (BALF leukocyte number was the primary endpoint in both models as this is also a primary endpoint in early clinical studies. Results To start, we confirmed that the inflammatory phenotypes were different after acute (3 days versus chronic (12 weeks CSE. The inflammation in the acute systems was predominantly neutrophilic, while in the more chronic CSE systems BALF neutrophils (PMNs, macrophage and lymphocyte numbers were all increased (p Conclusions These results demonstrate that the acute, prophylactic systems can be used to identify compounds with therapeutic potential, but may not predict a compound's efficacy in chronic smoke exposure models.

  13. IL-17 receptor A and adenosine deaminase 2 deficiency in siblings with recurrent infections and chronic inflammation.

    Science.gov (United States)

    Fellmann, Florence; Angelini, Federica; Wassenberg, Jacqueline; Perreau, Matthieu; Arenas Ramirez, Natalia; Simon, Gregoire; Boyman, Onur; Demaria, Olivier; Christen-Zaech, Stephanie; Hohl, Daniel; Belfiore, Marco; von Scheven-Gete, Annette; Gilliet, Michel; Bochud, Pierre-Yves; Perrin, Yannick; Beck Popovic, Maya; Bart, Pierre-Alexandre; Beckmann, Jacques S; Martinet, Danielle; Hofer, Michaël

    2016-04-01

    Data on patients affected by chronic mucocutaneous candidiasis underscore the preponderant role of IL-17 receptor A (IL-17RA) in preserving mucocutaneous immunity. Little is known about the role of adenosine deaminase (ADA) 2 in regulation of immune responses, although recent reports linked ADA2 deficiency with inflammation and vasculitis. We sought to investigate the mechanisms of chronic inflammation and vasculitis in a child lacking IL-17RA and ADA2 to identify therapeutic targets. We report a family with 2 siblings who have had recurrent mucocutaneous infections with Candida albicans and Staphylococcus aureus and chronic inflammatory disease and vasculitis since early childhood, which were refractory to classical treatments. Array-based comparative genomic hybridization analysis showed that both siblings are homozygous for a 770-kb deletion on chr22q11.1 encompassing both IL17RA and cat eye critical region 1 (CECR1). Immunologic studies were carried out by means of flow cytometry, ELISA, and RIA. As expected, in the affected child we found a lack of IL-17RA expression, which implies a severe malfunction in the IL-17 signaling pathway, conferring susceptibility to recurrent mucocutaneous infections. Surprisingly, we detected an in vitro and in vivo upregulation of proinflammatory cytokines, notably IL-1β and TNF-α, which is consistent with the persistent systemic inflammation. This work emphasizes the utility of whole-genome analyses combined with immunologic investigation in patients with unresolved immunodeficiency. This approach is likely to provide an insight into immunologic pathways and mechanisms of disease. It also provides molecular evidence for more targeted therapies. In addition, our report further corroborates a potential role of ADA2 in modulating immunity and inflammation. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  14. Swimming attenuates inflammation, oxidative stress, and apoptosis in a rat model of dextran sulfate sodium-induced chronic colitis.

    Science.gov (United States)

    Qin, Ling; Yao, Zhi-Qiang; Chang, Qi; Zhao, Ya-Li; Liu, Ning-Ning; Zhu, Xiao-Shan; Liu, Qin-Qin; Wang, Li-Feng; Yang, An-Gang; Gao, Chun-Fang; Li, Jun-Tang

    2017-01-31

    Increasing evidence suggests that regular physical exercise suppresses chronic inflammation. However, the potential inhibitory effects of swimming on dextran sulfate sodium (DSS)-induced chronic colitis, and its underlying mechanisms, remain unclear. In this study, rats were orally administered DSS to induce chronic colitis, and subsequently treated with or without swimming exercise. A 7-week swimming program (1 or 1.5 hours per day, 5 days per week) ameliorated DSS-caused colon shortening, colon barrier disruption, spleen enlargement, serum LDH release, and reduction of body weight gain. Swimming for 1.5 hours per day afforded greater protection than 1 hour per day. Swimming ameliorated DSS-induced decrease in crypt depth, and increases in myeloperoxidase activity, infiltration of Ly6G+ neutrophils and TNF-α- and IFN-γ-expressing CD3+ T cells, as well as fecal calprotectin and lactoferrin. Swimming inhibited pro-inflammatory cytokine and chemokine production and decreased the protein expression of phosphorylated nuclear factor-κB p65 and cyclooxygenase 2, whereas it elevated interleukin-10 levels. Swimming impeded the generation of reactive oxygen species, malondialdehyde, and nitric oxide; however, it boosted glutathione levels, total antioxidant capacity, and superoxide dismutase and glutathione peroxidase activities. Additionally, swimming decreased caspase-3 activity and expression of apoptosis-inducing factor, cytochrome c, Bax, and cleaved-caspase-3, but increased Bcl-2 levels. Overall, these results suggest that swimming exerts beneficial effects on DSS-induced chronic colitis by modulating inflammation, oxidative stress, and apoptosis.

  15. Neuronal and epithelial cell rescue resolves chronic systemic inflammation in the lipid storage disorder Niemann-Pick C.

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    Lopez, Manuel E; Klein, Andrés D; Hong, Jennifer; Dimbil, Ubah J; Scott, Matthew P

    2012-07-01

    Chronic systemic inflammation is thought to be a major contributor to metabolic and neurodegenerative diseases. Since inflammatory components are shared among different disorders, targeting inflammation is an attractive option for mitigating disease. To test the significance of inflammation in the lipid storage disorder (LSD) Niemann-Pick C (NPC), we deleted the macrophage inflammatory gene Mip1a/Ccl3 from NPC diseased mice. Deletion of Ccl3 had been reported to delay neuronal loss in Sandhoff LSD mice by inhibiting macrophage infiltration. For NPC mice, in contrast, deleting Ccl3 did not retard neurodegeneration and worsened the clinical outcome. Depletion of visceral tissue macrophages also did not alter central nervous system (CNS) pathology and instead increased liver injury, suggesting a limited macrophage infiltration response into the CNS and a beneficial role of macrophage activity in visceral tissue. Prevention of neuron loss or liver injury, even at late stages in the disease, was achieved through specific rescue of NPC disease in neurons or in liver epithelial cells, respectively. Local epithelial cell correction was also sufficient to reduce the macrophage-associated pathology in lung tissue. These results demonstrate that elevated inflammation and macrophage activity does not necessarily contribute to neurodegeneration and tissue injury, and LSD defects in immune cells may not preclude an appropriate inflammatory response. We conclude that inflammation remains secondary to neuronal and epithelial cell dysfunction and does not irreversibly contribute to the pathogenic cascade in NPC disease. Without further exploration of possible beneficial roles of inflammatory mediators, targeting inflammation may not be therapeutically effective at ameliorating disease severity.

  16. Prolonged Pulmonary Exposure to Diesel Exhaust Particles Exacerbates Renal Oxidative Stress, Inflammation and DNA Damage in Mice with Adenine-Induced Chronic Renal Failure

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    Abderrahim Nemmar

    2016-05-01

    Full Text Available Background/Aims: Epidemiological evidence indicates that patients with chronic kidney diseases have increased susceptibility to adverse outcomes related to long-term exposure to particulate air pollution. However, mechanisms underlying these effects are not fully understood. Methods: Presently, we assessed the effect of prolonged exposure to diesel exhaust particles (DEP on chronic renal failure induced by adenine (0.25% w/w in feed for 4 weeks, which is known to involve inflammation and oxidative stress. DEP (0.5m/kg was intratracheally (i.t. instilled every 4th day for 4 weeks (7 i.t. instillation. Four days following the last exposure to either DEP or saline (control, various renal endpoints were measured. Results: While body weight was decreased, kidney weight increased in DEP+adenine versus saline+adenine or DEP. Water intake, urine volume, relative kidney weight were significantly increased in adenine+DEP versus DEP and adenine+saline versus saline. Plasma creatinine and urea increased and creatinine clearance decreased in adenine+DEP versus DEP and adenine+saline versus saline. Tumor necrosis factor α, lipid peroxidation and reactive oxygen species were significantly increased in adenine+DEP compared with either DEP or adenine+saline. The antioxidant calase was significantly decreased in adenine+DEP compared with either adenine+saline or DEP. Notably, renal DNA damage was significantly potentiated in adenine+DEP compared with either adenine+saline or DEP. Similarly, systolic blood pressure was increased in adenine+DEP versus adenine+saline or DEP, and in DEP versus saline. Histological evaluation revealed more collagen deposition, higher number of necrotic cell counts and dilated tubules, cast formation and collapsing glomeruli in adenine+DEP versus adenine+saline or DEP. Conclusion: Prolonged pulmonary exposure to diesel exhaust particles worsen renal oxidative stress, inflammation and DNA damage in mice with adenine-induced chronic

  17. Decreases in colonic and systemic inflammation in chronic HIV infection after IL-7 administration.

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    Irini Sereti

    2014-01-01

    Full Text Available Despite antiretroviral therapy (ART, some HIV-infected persons maintain lower than normal CD4(+ T-cell counts in peripheral blood and in the gut mucosa. This incomplete immune restoration is associated with higher levels of immune activation manifested by high systemic levels of biomarkers, including sCD14 and D-dimer, that are independent predictors of morbidity and mortality in HIV infection. In this 12-week, single-arm, open-label study, we tested the efficacy of IL-7 adjunctive therapy on T-cell reconstitution in peripheral blood and gut mucosa in 23 ART suppressed HIV-infected patients with incomplete CD4(+ T-cell recovery, using one cycle (consisting of three subcutaneous injections of recombinant human IL-7 (r-hIL-7 at 20 µg/kg. IL-7 administration led to increases of both CD4(+ and CD8(+ T-cells in peripheral blood, and importantly an expansion of T-cells expressing the gut homing integrin α4β7. Participants who underwent rectosigmoid biopsies at study baseline and after treatment had T-cell increases in the gut mucosa measured by both flow cytometry and immunohistochemistry. IL-7 therapy also resulted in apparent improvement in gut barrier integrity as measured by decreased neutrophil infiltration in the rectosigmoid lamina propria 12 weeks after IL-7 administration. This was also accompanied by decreased TNF and increased FOXP3 expression in the lamina propria. Plasma levels of sCD14 and D-dimer, indicative of systemic inflammation, decreased after r-hIL-7. Increases of colonic mucosal T-cells correlated strongly with the decreased systemic levels of sCD14, the LPS coreceptor - a marker of monocyte activation. Furthermore, the proportion of inflammatory monocytes expressing CCR2 was decreased, as was the basal IL-1β production of peripheral blood monocytes. These data suggest that administration of r-hIL-7 improves the gut mucosal abnormalities of chronic HIV infection and attenuates the systemic inflammatory and coagulation

  18. Prescribing Optimal Nutrition and Physical Activity as “First-Line” Interventions for Best Practice Management of Chronic Low-Grade Inflammation Associated with Osteoarthritis: Evidence Synthesis

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    Elizabeth Dean

    2012-01-01

    Full Text Available Low-grade inflammation and oxidative stress underlie chronic osteoarthritis. Although best-practice guidelines for osteoarthritis emphasize self-management including weight control and exercise, the role of lifestyle behavior change to address chronic low-grade inflammation has not been a focus of first-line management. This paper synthesizes the literature that supports the idea in which the Western diet and inactivity are proinflammatory, whereas a plant-based diet and activity are anti-inflammatory, and that low-grade inflammation and oxidative stress underlying osteoarthritis often coexist with lifestyle-related risk factors and conditions. We provide evidence-informed recommendations on how lifestyle behavior change can be integrated into “first-line” osteoarthritis management through teamwork and targeted evidence-based interventions. Healthy living can be exploited to reduce inflammation, oxidative stress, and related pain and disability and improve patients’ overall health. This approach aligns with evidence-based best practice and holds the promise of eliminating or reducing chronic low-grade inflammation, attenuating disease progression, reducing weight, maximizing health by minimizing a patient’s risk or manifestations of other lifestyle-related conditions hallmarked by chronic low-grade inflammation, and reducing the need for medications and surgery. This approach provides an informed cost effective basis for prevention, potential reversal, and management of signs and symptoms of chronic osteoarthritis and has implications for research paradigms in osteoarthritis.

  19. Are PTH levels related to oxidative stress and inflammation in chronic kidney disease patients on hemodialysis?

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    Marcel Jaqueto

    Full Text Available Abstract Introduction: Patients at end stage renal disease have higher levels of inflammation and oxidative stress than the general population. Many factors contribute to these issues, and the parathyroid hormone (PTH is also implicated. Objective: The study was conducted in order to assess the relationship between PTH levels and inflammation and oxidative stress in hemodialysis patients. Methods: Cross-sectional study with patients of two hemodialysis facilities in Londrina, Brazil. Patients with other conditions known to generate oxidative stress and inflammation were excluded. Blood levels of PTH and biochemical parameters of inflammation (interleukins 1 and 6, tumor necrosis factor-alpha and oxidative stress (total plasma antioxidant capacity, malonic dialdehyde, lipid hydroperoxidation, advanced oxidation protein products, quantification of nitric oxide metabolites, and 8-isoprostane were measured before a dialysis session. Then, we made correlation analyses between PTH levels - either as the continuous variable or categorized into tertiles-, and inflammatory and oxidative stress biomarkers. Results: PTH did not show any correlation with the tested inflammation and oxidative stress parameters, nor as continuous variable neither as categorical variable. Conclusion: In this descriptive study, the results suggest that the inflammation and oxidative stress of hemodialysis patients probably arise from mechanisms other than secondary hyperparathyroidism.

  20. Chronic ethanol feeding promotes azoxymethane and dextran sulfate sodium-induced colonic tumorigenesis potentially by enhancing mucosal inflammation

    International Nuclear Information System (INIS)

    Shukla, Pradeep K.; Chaudhry, Kamaljit K.; Mir, Hina; Gangwar, Ruchika; Yadav, Nikki; Manda, Bhargavi; Meena, Avtar S.; Rao, RadhaKrishna

    2016-01-01

    Alcohol consumption is one of the major risk factors for colorectal cancer. However, the mechanism involved in this effect of alcohol is unknown. We evaluated the effect of chronic ethanol feeding on azoxymethane and dextran sulfate sodium (AOM/DSS)-induced carcinogenesis in mouse colon. Inflammation in colonic mucosa was assessed at a precancerous stage by evaluating mucosal infiltration of neutrophils and macrophages, and analysis of cytokine and chemokine gene expression. Chronic ethanol feeding significantly increased the number and size of polyps in colon of AOM/DSS treated mice. Confocal microscopic and immunoblot analyses showed a significant elevation of phospho-Smad, VEGF and HIF1α in the colonic mucosa. RT-PCR analysis at a precancerous stage indicated that ethanol significantly increases the expression of cytokines IL-1α, IL-6 and TNFα, and the chemokines CCL5/RANTES, CXCL9/MIG and CXCL10/IP-10 in the colonic mucosa of AOM/DSS treated mice. Confocal microscopy showed that ethanol feeding induces a dramatic elevation of myeloperoxidase, Gr1 and CD68-positive cells in the colonic mucosa of AOM/DSS-treated mice. Ethanol feeding enhanced AOM/DSS-induced suppression of tight junction protein expression and elevated cell proliferation marker, Ki-67 in the colonic epithelium. This study demonstrates that chronic ethanol feeding promotes colonic tumorigenesis potentially by enhancing inflammation and elevation of proinflammatory cytokines and chemokines

  1. Systemic and pulmonary inflammation is independent of skeletal muscle changes in patients with chronic obstructive pulmonary disease

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    Barker BL

    2014-09-01

    Full Text Available Bethan L Barker,1 Susan McKenna,1 Vijay Mistry,1 Mitesh Pancholi,1 Hemu Patel,2 Koirobi Haldar,3 Michael R Barer,3 Ian D Pavord,4 Michael C Steiner,1 Christopher E Brightling,1 Mona Bafadhel4 1Institute for Lung Health, NIHR Respiratory Biomedical Research Unit, Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom; 2Department of Clinical Microbiology, University Hospitals of Leicester NHS Trust, Leicester, United Kingdom; 3Department of Infection, Immunity, and Inflammation, University of Leicester, Leicester, United Kingdom; 4Respiratory Medicine Unit, Nuffield Department of Clinical Medicine, University of Oxford, Old Road Campus, Oxford, United Kingdom Background: Nutritional depletion is an important manifestation of chronic obstructive pulmonary disease (COPD, which has been related to systemic inflammation. It remains unclear to what degree airway inflammation contributes to the presence or progression of nutritional depletion. Objectives: To determine whether airway inflammation and lung bacterial colonization are related to nutritional status or predict progressive weight loss and muscle atrophy in patients with COPD. Methods: Body composition using dual energy X-ray absorptiometry, indices of airway inflammation, and bacterial colonization were measured in 234 COPD patients. Systemic inflammation was assessed from serum C reactive protein (CRP and circulating total and differential leukocyte counts. Nutritional depletion was defined as a body mass index (BMI less than 21 kg/m2 and/or fat-free mass index (FFMI less than 15 or 17 kg/m2 in women and men, respectively. FFMI was calculated as the fat-free mass (FFM corrected for body surface area. Measurements were repeated in 94 patients after a median 16-month follow-up. Regression analysis was used to assess the relationships of weight change and FFM change with indices of bacterial colonization and airway and systemic inflammation

  2. Diabetes induces stable intrinsic changes to myeloid cells that contribute to chronic inflammation during wound healing in mice

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    Pauline Bannon

    2013-11-01

    Acute inflammation in response to injury is a tightly regulated process by which subsets of leukocytes are recruited to the injured tissue and undergo behavioural changes that are essential for effective tissue repair and regeneration. The diabetic wound environment is characterised by excessive and prolonged inflammation that is linked to poor progression of healing and, in humans, the development of diabetic foot ulcers. However, the underlying mechanisms contributing to excessive inflammation remain poorly understood. Here we show in a murine model that the diabetic environment induces stable intrinsic changes in haematopoietic cells. These changes lead to a hyper-responsive phenotype to both pro-inflammatory and anti-inflammatory stimuli, producing extreme M1 and M2 polarised cells. During early wound healing, myeloid cells in diabetic mice show hyperpolarisation towards both M1 and M2 phenotypes, whereas, at late stages of healing, when non-diabetic macrophages have transitioned to an M2 phenotype, diabetic wound macrophages continue to display an M1 phenotype. Intriguingly, we show that this population predominantly consists of Gr-1+ CD11b+ CD14+ cells that have been previously reported as ‘inflammatory macrophages’ recruited to injured tissue in the early stages of wound healing. Finally, we show that this phenomenon is directly relevant to human diabetic ulcers, for which M2 polarisation predicts healing outcome. Thus, treatments focused at targeting this inflammatory cell subset could prove beneficial for pathological tissue repair.

  3. The effect of systemic treatments on periostin expression reflects their interference with the eosinophilic inflammation in chronic rhinosinusitis with nasal polyps

    NARCIS (Netherlands)

    de Schryver, E.; Derycke, L.; Calus, L.; Holtappels, G.; Hellings, P. W.; van Zele, T.; Bachert, C.; Gevaert, P.

    2017-01-01

    Background: Periostin is a recently discovered biomarker for eosinophilic inflammation. Chronic rhinosinusitis with nasal polyps is a T-helper 2-skewed chronic inflammatory airway disease. Medical treatments aim to relieve symptoms and maintain clinical control by interfering with the inflammatory

  4. [The relationship between pulmonary arterial and small airway inflammation in smokers with and without chronic obstructive pulmonary disease].

    Science.gov (United States)

    Lao, Qifang; Zeng, Xiaoliang; Zhong, Xiaoning; Zhang, Jianquan; He, Zhiyi

    2014-12-01

    To investigate the relationship between pulmonary arterial and small airway inflammation in smokers with normal lung function and smokers with chronic obstructive pulmonary disease (COPD). Patients requiring lung resection for peripheral lung cancer were divided into group A (nonsmokers with normal lung function, n = 10), group B (smokers with normal lung function, n = 13) and group C (smokers with stable COPD, n = 10). Normal pulmonary tissue was obtained more than 5 cm away from cancer lesion. The pathomorphological changes of the pulmonary muscularized arteries (MA) and small airways were observed by HE and Victoria blue-Van Gieson's stains.Lymphocytes infiltrated in the MA and small airways were observed by immunohistochemical methods. The characteristics and the correlations between pulmonary arterial inflammation and small airway inflammation were analyzed. The thickness of MA wall in the three groups was (119 ± 11), (139 ± 25) and (172 ± 28) µm respectively. The total small airway pathology score was (49 ± 10), (101 ± 34) and (163 ± 36) respectively. The score in group B and C was significantly higher than that in group A (P 0.05). The infiltration of CD(+)(3)T-lymphocytes and CD(+)(8)T-lymphocytes in the whole layer of MA was positively correlated with the total small airway pathology score respectively (r = 0.431,0.633, P arteries and small airways is the same kind of inflammation, mainly in the adventitia of pulmonary arteries and small airways. They are a part of pulmonary inflammation in COPD and promote the development of COPD.

  5. Inhibition of chronic prostate inflammation by hyaluronic acid through an immortalized human prostate stromal cell line model.

    Science.gov (United States)

    Liu, Ming-Che; Chen, Wei-Hong; Chiou, Chi-Sheng; Lo, Wen-Cheng; Dubey, Navneet Kumar; Chen, Yu-Chin; Lai, Wen-Fu T; Yeh, Shauh-Der; Chiang, Han-Sun; Deng, Win-Ping

    2017-01-01

    Benign prostatic hyperplasia (BPH) is the most common urologic disease among elderly men. A well-established in vitro cell model is required to determine the therapeutic mechanism of BPH inflammation. In this study, we attempted to establish an immortalized human prostate stromal cell line by transfecting with HPV-16 E6/E7 and designated as ihPSC. No significant difference was found in fibroblast-like morphology between primary hPSC and ihPSC. The ihPSC possessed a significantly higher cell proliferation rate than primary hPSC. The prostate-specific markers and proteins including cytoskeleton (α-SMA and vimentin) and smooth muscle (calponin), especially the androgen receptor (AR) were also examined in ihPSC, almost identical to the primary hPSC. To create an in vitro model featuring chronic prostatic inflammation, ihPSC was stimulated with IFN-γ+IL-17 and then treated with the high molecular weight hyaluronic acid hylan G-F 20 as an alternative strategy for inhibiting BPH inflammation. Hylan G-F 20 could dose-dependently diminish the inflammation-induced proliferation in ihPSC. The enhanced expressions of inflammatory molecules including IL-1β, IL-6, IL-8, cyclooxygenase 2 (COX2), inducible nitrogen oxide synthase (iNOS), and Toll-like receptor 4 (TLR4) were all abolished by hylan G-F 20. For inflammatory signaling, hylan G-F 20 can also diminish the IFN-γ+IL-17-increased expression of iNOS and p65 in ihPSC. These findings suggest that ihPSC could provide a mechanism-based platform for investigating prostate inflammation. The hylan G-F 20 showed strong anti-inflammatory effects by decreasing inflammatory cytokines and signalings in the ihPSC, indicating its therapeutic potentials in BPH treatment in the future.

  6. Inhibition of chronic prostate inflammation by hyaluronic acid through an immortalized human prostate stromal cell line model

    Science.gov (United States)

    Liu, Ming-Che; Chen, Wei-Hong; Chiou, Chi-Sheng; Lo, Wen-Cheng; Dubey, Navneet Kumar; Chen, Yu-Chin; Lai, Wen-Fu T.; Yeh, Shauh-Der; Chiang, Han-Sun; Deng, Win-Ping

    2017-01-01

    Benign prostatic hyperplasia (BPH) is the most common urologic disease among elderly men. A well-established in vitro cell model is required to determine the therapeutic mechanism of BPH inflammation. In this study, we attempted to establish an immortalized human prostate stromal cell line by transfecting with HPV-16 E6/E7 and designated as ihPSC. No significant difference was found in fibroblast-like morphology between primary hPSC and ihPSC. The ihPSC possessed a significantly higher cell proliferation rate than primary hPSC. The prostate-specific markers and proteins including cytoskeleton (α-SMA and vimentin) and smooth muscle (calponin), especially the androgen receptor (AR) were also examined in ihPSC, almost identical to the primary hPSC. To create an in vitro model featuring chronic prostatic inflammation, ihPSC was stimulated with IFN-γ+IL-17 and then treated with the high molecular weight hyaluronic acid hylan G-F 20 as an alternative strategy for inhibiting BPH inflammation. Hylan G-F 20 could dose-dependently diminish the inflammation-induced proliferation in ihPSC. The enhanced expressions of inflammatory molecules including IL-1β, IL-6, IL-8, cyclooxygenase 2 (COX2), inducible nitrogen oxide synthase (iNOS), and Toll-like receptor 4 (TLR4) were all abolished by hylan G-F 20. For inflammatory signaling, hylan G-F 20 can also diminish the IFN-γ+IL-17-increased expression of iNOS and p65 in ihPSC. These findings suggest that ihPSC could provide a mechanism-based platform for investigating prostate inflammation. The hylan G-F 20 showed strong anti-inflammatory effects by decreasing inflammatory cytokines and signalings in the ihPSC, indicating its therapeutic potentials in BPH treatment in the future. PMID:28558037

  7. Chronic IL-33 expression predisposes to virus-induced asthma exacerbations by increasing type 2 inflammation and dampening antiviral immunity.

    Science.gov (United States)

    Werder, Rhiannon B; Zhang, Vivian; Lynch, Jason P; Snape, Natale; Upham, John W; Spann, Kirsten; Phipps, Simon

    2017-09-22

    Rhinovirus infection triggers acute asthma exacerbations. IL-33 is an instructive cytokine of type 2 inflammation whose expression is associated with viral load during experimental rhinovirus infection of asthmatic patients. We sought to determine whether anti-IL-33 therapy is effective during disease progression, established disease, or viral exacerbation using a preclinical model of chronic asthma and in vitro human primary airway epithelial cells (AECs). Mice were exposed to pneumonia virus of mice and cockroach extract in early and later life and then challenged with rhinovirus to model disease onset, progression, and chronicity. Interventions included anti-IL-33 or dexamethasone at various stages of disease. AECs were obtained from asthmatic patients and healthy subjects and treated with anti-IL-33 after rhinovirus infection. Anti-IL-33 decreased type 2 inflammation in all phases of disease; however, the ability to prevent airway smooth muscle growth was lost after the progression phase. After the chronic phase, IL-33 levels were persistently high, and rhinovirus challenge exacerbated the type 2 inflammatory response. Treatment with anti-IL-33 or dexamethasone diminished exacerbation severity, and anti-IL-33, but not dexamethasone, promoted antiviral interferon expression and decreased viral load. Rhinovirus replication was higher and IFN-λ levels were lower in AECs from asthmatic patients compared with those from healthy subjects. Anti-IL-33 decreased rhinovirus replication and increased IFN-λ levels at the gene and protein levels. Anti-IL-33 or dexamethasone suppressed the magnitude of type 2 inflammation during a rhinovirus-induced acute exacerbation; however, only anti-IL-33 boosted antiviral immunity and decreased viral replication. The latter phenotype was replicated in rhinovirus-infected human AECs, suggesting that anti-IL-33 therapy has the additional benefit of enhancing host defense. Copyright © 2017 American Academy of Allergy, Asthma

  8. Etiologic and clinical analysis of chronic complex anal and rectal inflammation in children less than 3 years old.

    Science.gov (United States)

    Huang, Yanlei; Zheng, Shan; Xiao, Xianmin

    2014-01-01

    To analyze the etiology and clinical diagnostic method for chronic complex anal and rectal inflammation in children less than 3 years old. Seven children (5 males and 2 females; 1 year 8 months to 3 years of age at the time of physician evaluation) with chronic complex anal and rectal inflammation were enrolled between May 2008 and May 2013 at our hospital. Clinical history, results of auxiliary examinations, and empirical treatment of the children were analyzed retrospectively combined with the etiologic diagnosis. Four patients were confirmed to have Crohn's disease and one patient was confirmed to have intestinal tuberculosis; two patients were suspected to have Crohn's disease. Anemia and low pre-albumin level were common (seven patients); serologic testing revealed four patients with elevated IgG levels and seven patients with elevated IgA levels; there were no patients with positive tuberculosis antibody titers and two patients were weakly positive for C-ANCA (one patient with Crohn's disease and one patient intestinal tuberculosis). Colonoscopies revealed that the entire colon was affected in one patient, the left hemicolon was affected in four patients, and the sigmoid colon and rectum were affected in two patients. Two patients with Crohn's disease and one patient with intestinal tuberculosis were diagnosed by colonoscopies in combination with histopathologic examinations. Two patients with Crohn's disease were confirmed after empirical drug treatment, and two other patients were not definitely diagnosed. The possibility of Crohn's disease or intestinal tuberculosis should be considered in the clinical diagnosis of complex chronic anal and rectal inflammation in younger children. Local surgery is sometimes unnecessary. Empirical drug treatment should be used if necessary.

  9. Inflammation and endothelial dysfunction are associated with retinopathy: the Hoorn study

    NARCIS (Netherlands)

    Hecke, van M.V.; Dekker, J.M.; Nijpels, M.G.A.A.M.; Moll, A.C.; Heine, R.J.; Bouter, L.M.; Polak, B.C.P.; Stehouwer, C.D.A.

    2005-01-01

    AIMS/HYPOTHESIS: The exact pathogenesis of retinopathy in diabetic and non-diabetic individuals is incompletely understood, but may involve chronic low-grade inflammation and dysfunction of the vascular endothelium. The aim of this study was to investigate the association of inflammation and

  10. Inflammation and endothelial dysfunction are associated with retinopathy: the Hoorn study

    NARCIS (Netherlands)

    van Hecke, M.V.; Dekker, J.M.; Nijpels, M.G.A.A.M.; Moll, A.C.; Heine, R.J.; Bouter, L.M.; Polak, B.C.P.; Stehouwer, C.D.A.

    2005-01-01

    Aims/hypothesis: The exact pathogenesis of retinopathy in diabetic and non-diabetic individuals is incompletely understood, but may involve chronic low-grade inflammation and dysfunction of the vascular endothelium. The aim of this study was to investigate the association of inflammation and

  11. Grape polyphenols supplementation reduces muscle atrophy in a mouse model of chronic inflammation.

    Science.gov (United States)

    Lambert, Karen; Coisy-Quivy, Marjorie; Bisbal, Catherine; Sirvent, Pascal; Hugon, Gerald; Mercier, Jacques; Avignon, Antoine; Sultan, Ariane

    2015-10-01

    Polyphenols (PP) have demonstrated beneficial effects on low-grade inflammation and oxidative stress; however, little is known about their effect on highly inflamed muscle. The purposes of this study were (i) to evaluate muscle alteration induced by high-grade inflammation, and (ii) to test the effects of red grape PP supplementation on these alterations. We used a transgenic mice model (transforming growth factor [TGF] mice) to develop a high T cell-dependent inflammation and C57 BL/6 control (CTL) mice model. Skeletal muscles of TGF and CTL mice were investigated for inflammation, atrophy and oxidative stress markers. Isolated mitochondria from hindlimb muscles were used for respiration with pyruvate as substrate and oxidative damages were measured by Western blot. TGF mice were supplemented with a mixture of red grape polyphenols (50 mg/kg/d) for 4 wk. Data were analyzed by one-way analysis of variance (ANOVA) and post hoc Bonferroni's multiple comparison tests. TGF mice presented skeletal muscle inflammation, oxidative stress, mitochondrial alteration and muscle atrophy. Atrophy was associated with two distinct pathways: (i) one linked to inflammation, NF-κB activation and increased ubiquitin ligase expression, and (ii) one dependent on reactive oxygen species (ROS) production leading to damaged mitochondria accumulation and activation of caspase-9 and 3. Supplementation of TGF mice with a mixture of red grape polyphenols (50 mg/kg/d) for 4 wk improved mitochondrial function and highly decreased caspases activation, which allowed muscle atrophy mitigation. These observations suggest that nutritional dosages of red grape polyphenols might be beneficial for reducing skeletal muscle atrophy, even in a high-grade inflammation environment. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Differential role of lipocalin-2 during immune-complex mediated acute and chronic inflammation

    Science.gov (United States)

    Shashidharamurthy, Rangaiah; Machiah, Deepa; Aitken, Jesse D; Putty, Kalyani; Srinivasan, Gayathri; Chassaing, Benoit; Parkos, Charles A; Selvaraj, Periasamy; Vijay-Kumar, Matam

    2013-01-01

    Objectives Lipocalin-2 (Lcn2) is an innate immune protein expressed by a variety of cells and is highly upregulated during several pathological conditions including immune-complex (IC) mediated inflammatory/autoimmune disorders. However, the function of Lcn2 during IC-mediated inflammation is largely unknown. Therefore our objective was to investigate the role of Lcn2 in IC-mediated diseases. Methods The upregulation of Lcn2 was determined by ELISA in three different mouse models of IC-mediated autoimmune disease: systemic lupus erythematosus, collagen-induced arthritis and serum-induced arthritis. The in vivo role of Lcn2 during IC-mediated inflammation was investigated using Lcn2 knockout (Lcn2KO) mice and their wild type (WT) littermates. Results Lcn2 levels were significantly elevated in all the three autoimmune disease models. Further, in an acute skin inflammation model, Lcn2KO mice demonstrated a 50% reduction in inflammation with histopathological analysis revealing strikingly reduced immune cell infiltration compared to WT mice. Administration of recombinant Lcn2 to Lcn2KO mice restored inflammation to levels observed in WT mice. Neutralization of Lcn2 using a monoclonal antibody significantly reduced inflammation in WT mice. In contrast, Lcn2KO mice developed more severe serum-induced arthritis compared to WT mice. Histological analysis revealed extensive tissue and bone destruction with significantly reduced neutrophil infiltration but considerably more macrophage migration in Lcn2KO mice when compared to WT. Conclusion These results demonstrate that Lcn2 may regulate immune cell recruitment to the site of inflammation, a process essential for the controlled initiation, perpetuation and resolution of inflammatory processes. Thus, Lcn2 may present a promising target in the treatment of IC-mediated inflammatory/autoimmune diseases. PMID:23280250

  13. Association of Lifecourse Socioeconomic Status with Chronic Inflammation and Type 2 Diabetes Risk: The Whitehall II Prospective Cohort Study

    Science.gov (United States)

    Stringhini, Silvia; Batty, G. David; Bovet, Pascal; Shipley, Martin J.; Marmot, Michael G.; Kumari, Meena; Tabak, Adam G.; Kivimäki, Mika

    2013-01-01

    Background Socioeconomic adversity in early life has been hypothesized to “program” a vulnerable phenotype with exaggerated inflammatory responses, so increasing the risk of developing type 2 diabetes in adulthood. The aim of this study is to test this hypothesis by assessing the extent to which the association between lifecourse socioeconomic status and type 2 diabetes incidence is explained by chronic inflammation. Methods and Findings We use data from the British Whitehall II study, a prospective occupational cohort of adults established in 1985. The inflammatory markers C-reactive protein and interleukin-6 were measured repeatedly and type 2 diabetes incidence (new cases) was monitored over an 18-year follow-up (from 1991–1993 until 2007–2009). Our analytical sample consisted of 6,387 non-diabetic participants (1,818 women), of whom 731 (207 women) developed type 2 diabetes over the follow-up. Cumulative exposure to low socioeconomic status from childhood to middle age was associated with an increased risk of developing type 2 diabetes in adulthood (hazard ratio [HR] = 1.96, 95% confidence interval: 1.48–2.58 for low cumulative lifecourse socioeconomic score and HR = 1.55, 95% confidence interval: 1.26–1.91 for low-low socioeconomic trajectory). 25% of the excess risk associated with cumulative socioeconomic adversity across the lifecourse and 32% of the excess risk associated with low-low socioeconomic trajectory was attributable to chronically elevated inflammation (95% confidence intervals 16%–58%). Conclusions In the present study, chronic inflammation explained a substantial part of the association between lifecourse socioeconomic disadvantage and type 2 diabetes. Further studies should be performed to confirm these findings in population-based samples, as the Whitehall II cohort is not representative of the general population, and to examine the extent to which social inequalities attributable to chronic inflammation are reversible

  14. Angiotensin-(1?7) inhibits inflammation and oxidative stress to relieve lung injury induced by chronic intermittent hypoxia in rats

    OpenAIRE

    Lu, W.; Kang, J.; Hu, K.; Tang, S.; Zhou, X.; Yu, S.; Li, Y.; Xu, L.

    2016-01-01

    Obstructive sleep apnea is associated with inflammation and oxidative stress in lung tissues and can lead to metabolic abnormalities. We investigated the effects of angiotensin1–7 [Ang-(1–7)] on lung injury in rats induced by chronic intermittent hypoxia (CIH). We randomly assigned 32 male Sprague-Dawley rats (180–200 g) to normoxia control (NC), CIH-untreated (uCIH), Ang-(1–7)-treated normoxia control (N-A), and Ang-(1–7)-treated CIH (CIH-A) groups. Oxidative stress biomarkers were measured ...

  15. Chronic Hepatitis B Virus Infection: The Relation between Hepatitis B Antigen Expression, Telomere Length, Senescence, Inflammation and Fibrosis.

    Directory of Open Access Journals (Sweden)

    Phaedra M Tachtatzis

    Full Text Available Chronic Hepatitis B virus (HBV infection can lead to the development of chronic hepatitis, cirrhosis and hepatocellular carcinoma. We hypothesized that HBV might accelerate hepatocyte ageing and investigated the effect of HBV on hepatocyte cell cycle state and biological age. We also investigated the relation between inflammation, fibrosis and cell cycle phase.Liver samples from patients with chronic HBV (n = 91, normal liver (n = 55 and regenerating liver (n = 15 were studied. Immunohistochemistry for cell cycle phase markers and HBV antigens was used to determine host cell cycle phase. Hepatocyte-specific telomere length was evaluated by quantitative fluorescent in-situ hybridization (Q-FISH in conjunction with hepatocyte nuclear area and HBV antigen expression. The effects of induced cell cycle arrest and induced cellular senescence on HBV production were assessed in vitro.13.7% hepatocytes in chronic HBV had entered cell cycle, but expression of markers for S, G2 and M phase was low compared with regenerating liver. Hepatocyte p21 expression was increased (10.9% in chronic HBV and correlated with liver fibrosis. Mean telomere length was reduced in chronic HBV compared to normal. However, within HBV-affected livers, hepatocytes expressing HBV antigens had longer telomeres. Telomere length declined and hepatocyte nuclear size increased as HBV core antigen (HBcAg expression shifted from the nucleus to cytoplasm. Nuclear co-expression of HBcAg and p21 was not observed. Cell cycle arrest induced in vitro was associated with increased HBV production, in contrast to in vitro induction of cellular senescence, which had no effect.Chronic HBV infection was associated with hepatocyte G1 cell cycle arrest and accelerated hepatocyte ageing, implying that HBV induced cellular senescence. However, HBV replication was confined to biologically younger hepatocytes. Changes in the cellular location of HBcAg may be related to the onset of cellular senescence.

  16. Home-based pulmonary rehabilitation improves clinical features and systemic inflammation in chronic obstructive pulmonary disease patients

    Directory of Open Access Journals (Sweden)

    Nascimento ESP

    2015-03-01

    Full Text Available Eloisa Sanches Pereira do Nascimento,1 Luciana Maria Malosá Sampaio,1 Fabiana Sobral Peixoto-Souza,1 Fernanda Dultra Dias,1 Evelim Leal Freitas Dantas Gomes,1 Flavia Regina Greiffo,2 Ana Paula Ligeiro de Oliveira,2 Roberto Stirbulov,3 Rodolfo Paula Vieira,2 Dirceu Costa11Laboratory of Functional Respiratory Evaluation (LARESP, 2Laboratory of Pulmonary and Exercise Immunology (LABPEI, Nove de Julho University (UNINOVE, São Paulo, SP, Brazil; 3Department of Pneumology, Santa Casa University Hospital, São Paulo, SP, BrazilAbstract: Chronic obstructive pulmonary disease (COPD is a respiratory disease characterized by chronic airflow limitation that leads beyond the pulmonary changes to important systemic effects. COPD is characterized by pulmonary and systemic inflammation. However, increases in the levels of inflammatory cytokines in plasma are found even when the disease is stable. Pulmonary rehabilitation improves physical exercise capacity and quality of life and decreases dyspnea. The aim of this study was to evaluate whether a home-based pulmonary rehabilitation (HBPR program improves exercise tolerance in COPD patients, as well as health-related quality of life and systemic inflammation. This prospective study was conducted at the Laboratory of Functional Respiratory Evaluation, Nove de Julho University, São Paulo, Brazil. After anamnesis, patients were subjected to evaluations of health-related quality of life and dyspnea, spirometry, respiratory muscle strength, upper limbs incremental test, incremental shuttle walk test, and blood test for quantification of systemic inflammatory markers (interleukin [IL]-6 and IL-8. At the end of the evaluations, patients received a booklet containing the physical exercises to be performed at home, three times per week for 8 consecutive weeks. Around 25 patients were enrolled, and 14 completed the pre- and post-HBPR ratings. There was a significant increase in the walked distance and the maximal

  17. The Evaluation of the Role of Beta-Hydroxy Fatty Acids on Chronic Inflammation and Insulin Resistance

    Directory of Open Access Journals (Sweden)

    A. S. Soydan

    2006-01-01

    Full Text Available β-hydroxy fatty acids are a major component of lipid A moiety of lipopolysaccaride. We aimed to investigate the role of free β-hydroxy fatty acids on inflammation, as well as to evaluate their effects on cytokine release from human blood cells, and whether they exist in plasma of patients with chronic inflammatory diseases with/without insulin resistance. Peripheral venous blood was incubated with β-hydroxy lauric and β-hydroxy myristic acids (each 100 ng, 1 μg, 10 μg/mL up to 24 hours. Cytokines were measured from culture media and plasma. Free fatty acids and biochemical parameters were also measured from patients' plasma. Only β-hydroxy lauric acid significantly stimulated interleukin-6 production at 10 μg/mL compared to control (533.9±218.1 versus 438.3±219.6 pg/mL, P<.05. However, free β-hydroxy lauric and myristic acids were not found in patients' plasma. Therefore, free β-hydroxy lauric and myristic acids do not seem to have a role on sterile inflammation in chronic inflammatory diseases associated with insulin resistance.

  18. Whether, when and how chronic inflammation increases the risk of developing late-onset Alzheimer's disease

    NARCIS (Netherlands)

    Eikelenboom, P.; Hoozemans, J.J.M.; Veerhuis, R.; van Exel, E.; Rozemuller, A.J.M.; van Gool, W.A.

    2012-01-01

    Neuropathological studies have revealed the presence of a broad variety of inflammation-related proteins (complement factors, acute-phase proteins, pro-inflammatory cytokines) in Alzheimer's disease (AD) brains. These constituents of innate immunity are involved in several crucial pathogenic events

  19. High amylose resistant starch diet ameliorates oxidative stress, inflammation, and progression of chronic kidney disease

    Science.gov (United States)

    Inflammation is a major mediator of CKD progression and is partly driven by altered gut microbiome and intestinal barrier disruption, events which are caused by: urea influx in the intestine resulting in dominance of urease-possessing bacteria; disruption of epithelial barrier by urea-derived ammoni...

  20. A resistant starch fiber diet ameliorates oxidative stress, inflammation, and progression of chronic kidney disease (CKD)

    Science.gov (United States)

    Inflammation is a constant feature and a major mediator of CKD progression. It is, in part, driven by altered gut microbiome and disruption of intestinal epithelial barrier, events which are primarily caused by: 1- urea influx in the intestine resulting in dominance of urease-possessing bacteria; 2-...

  1. Saponins isolated from roots of Chlorophytum borivilianum reduce acute and chronic inflammation and histone deacetylase.

    Science.gov (United States)

    Lande, Anirudha A; Ambavade, Shirishkumar D; Swami, Uma S; Adkar, Prafulla P; Ambavade, Prashant D; Waghamare, Arun B

    2015-01-01

    The roots of Chlorophytum borivilanum are used in traditional medicine for the treatment of arthritis and inflammation. The aim of the work was to evaluate the anti-inflammatory activity of isolated saponins from Chlorophytum borivilianum (ISCB). The ISCB was screened using the carrageenan-induced paw edema, histamine-induced paw edema, cotton pellet-induced granuloma, and Freund's adjuvant-induced arthritis in rats at orally administered doses of 3, 10, and 30 mg/kg. Effect of ISCB on histone deacetylase (HDAC) level was measured by the HDAC assay at the highest dose (30 mg/kg). The results showed that the ISCB significantly reduced carrageenan-induced inflammation, histamine-induced inflammation, cotton pellet-induced granuloma and Freund's adjuvant-induced arthritis in rats. The ISCB at a dose of 30 mg/kg significantly inhibited HDAC level in rat paw tissue. It is concluded that saponins isolated from roots of C. borivilianum possess anti-inflammatory and anti-arthritic properties. ISCB may act by inhibiting histamine, prostaglandin and HDAC. This suggests that ISCBs have potential for therapeutic use in the treatment of inflammation and arthritis.

  2. YKL-40: a novel marker shared by chronic inflammation and oncogenic transformation

    DEFF Research Database (Denmark)

    Roslind, Anne; Johansen, Julia S

    2009-01-01

    YKL-40, a member of 'mammalian chitinase-like proteins', is secreted by macrophages, neutrophils, chondrocytes, endothelial-, vascular smooth muscle-, and cancer cells. High serum YKL-40 is a biomarker of poor prognosis in patients with cancer, inflammation and increased tissue remodelling. High...

  3. Home-based pulmonary rehabilitation improves clinical features and systemic inflammation in chronic obstructive pulmonary disease patients.

    Science.gov (United States)

    do Nascimento, Eloisa Sanches Pereira; Sampaio, Luciana Maria Malosá; Peixoto-Souza, Fabiana Sobral; Dias, Fernanda Dultra; Gomes, Evelim Leal Freitas Dantas; Greiffo, Flavia Regina; Ligeiro de Oliveira, Ana Paula; Stirbulov, Roberto; Vieira, Rodolfo Paula; Costa, Dirceu

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) is a respiratory disease characterized by chronic airflow limitation that leads beyond the pulmonary changes to important systemic effects. COPD is characterized by pulmonary and systemic inflammation. However, increases in the levels of inflammatory cytokines in plasma are found even when the disease is stable. Pulmonary rehabilitation improves physical exercise capacity and quality of life and decreases dyspnea. The aim of this study was to evaluate whether a home-based pulmonary rehabilitation (HBPR) program improves exercise tolerance in COPD patients, as well as health-related quality of life and systemic inflammation. This prospective study was conducted at the Laboratory of Functional Respiratory Evaluation, Nove de Julho University, São Paulo, Brazil. After anamnesis, patients were subjected to evaluations of health-related quality of life and dyspnea, spirometry, respiratory muscle strength, upper limbs incremental test, incremental shuttle walk test, and blood test for quantification of systemic inflammatory markers (interleukin [IL]-6 and IL-8). At the end of the evaluations, patients received a booklet containing the physical exercises to be performed at home, three times per week for 8 consecutive weeks. Around 25 patients were enrolled, and 14 completed the pre- and post-HBPR ratings. There was a significant increase in the walked distance and the maximal inspiratory pressure, improvements on two components from the health-related quality-of-life questionnaire, and a decrease in plasma IL-8 levels after the intervention. The HBPR is an important and viable alternative to pulmonary rehabilitation for the treatment of patients with COPD; it improves exercise tolerance, inspiratory muscle strength, quality of life, and systemic inflammation in COPD patients.

  4. An MRI assessment of chronic synovial-based inflammation in gout and its correlation with serum urate levels.

    Science.gov (United States)

    Carter, John D; Patelli, Michelle; Anderson, Scott R; Prakash, Neelesh; Rodriquez, Ernesto J; Bateman, Helen; Sterrett, Ashley; Valeriano, Joanne; Ricca, Louis R

    2015-02-01

    It is unclear when the synovial-based inflammatory process of gout begins. The aim of this study was to determine the percentage of patients with inter-critical gout who have chronic synovial-based inflammation as evidenced by synovial pannus on a contrast-enhanced magnetic resonance imaging (MRI) of their most involved joint and determine if the presence and/or severity correlates with their serum urate levels. All patients received a 3 T MRI of their index joint, serum urate level, CRP, and creatinine. The primary endpoint was to determine the prevalence of synovial pannus and the correlation of serum urate levels with the presence and/or severity of the synovial pannus on that same joint. MRI erosions, tophi, swelling, effusion, and osteitis were also documented. Seventy-two of 74 subjects (90% men) completed the protocol. Fifty-three of 72 (74%) index joints were the first metatarsophalangeal joint. Thirty-nine (54.2%) of the patients were on urate-lowering therapy; 15 (20.8%) and 7 (9.7%) were taking colchicine or a NSAID daily, respectively. Of the 72 subjects, 63 (87.5%) had synovial pannus on their MRI with good inter-reader agreement between the two radiologists. The mean serum urate level was 7.93 mg/dL. There was no correlation with the presence (p = 0.33) or severity (p = 0.34) of synovial pannus and serum urate levels. There was also no correlation with the presence or severity of synovial pannus and the secondary endpoints. The majority of patients with inter-critical gout have evidence of chronic synovial-based inflammation. However, the presence and severity of this inflammation do not appear to correlate with serum urate levels.

  5. Basal inflammation and innate immune response in chronic multisite musculoskeletal pain

    NARCIS (Netherlands)

    Generaal, E.; Vogelzangs, N.; MacFarlane, G.J.; Geenen, R.; Smit, J.H.; Dekker, J.; Penninx, B.W.J.H.

    2014-01-01

    Dysregulation of the immune system may play a role in chronic pain, although study findings are inconsistent. This cross-sectional study examined whether basal inflammatory markers and the innate immune response are associated with the presence and severity of chronic multisite musculoskeletal pain.

  6. Inflammation Markers and Major Depressive Disorder in Patients With Chronic Heart Failure: Results From the Sertraline Against Depression and Heart Disease in Chronic Heart Failure Study.

    Science.gov (United States)

    Xiong, Glen L; Prybol, Kevin; Boyle, Stephen H; Hall, Russell; Streilein, Robert D; Steffens, David C; Krishnan, Ranga; Rogers, Joseph G; O'Connor, Christopher M; Jiang, Wei

    2015-09-01

    Major depressive disorder (MDD) and chronic heart failure (CHF) have in common heightening states of inflammation, manifested by elevated inflammation markers such as C-reactive protein. This study compared inflammatory biomarker profiles in patients with CHF and MDD to those without MDD. The study recruited patients admitted to inpatient care for acute heart failure exacerbations, after psychiatric diagnostic interview. Patients with Beck Depression Inventory (BDI) scores lower than 10 and with no history of depression served as the nondepressed reference group (n = 25). MDD severity was defined as follows: mild (BDI 10-15; n = 48), moderate (BDI 16-23; n = 51), and severe (BDI ≥ 24; n = 33). A Bio-Plex assay measured 18 inflammation markers. Ordinal logistic models were used to examine the association of MDD severity and biomarker levels. Adjusting for age, sex, statin use, body mass index, left ventricular ejection fraction, tobacco use, and New York Heart Association class, the MDD overall group variable was significantly associated with elevated interleukin (IL)-2 (p = .019), IL-4 (p = .020), IL-6 (p = .026), interferon-γ (p = .010), monocyte chemoattractant protein 1 (p = .002), macrophage inflammatory protein 1β (p = .003), and tumor necrosis factor α (p = .004). MDD severity subgroups had a greater probability of elevated IL-6, IL-8, interferon-γ, monocyte chemoattractant protein 1, macrophage inflammatory protein 1β, and tumor necrosis factor α compared with nondepressed group. The nondepressed group had greater probability of elevated IL-17 (p depression. Whether effective depression treatment will normalize the altered inflammation marker levels requires further study. ClinicalTrials.gov NCT00078286.

  7. Identification of a cytochrome P4502E1/Bid/C1q-dependent axis mediating inflammation in adipose tissue after chronic ethanol feeding to mice.

    Science.gov (United States)

    Sebastian, Becky M; Roychowdhury, Sanjoy; Tang, Hui; Hillian, Antoinette D; Feldstein, Ariel E; Stahl, Gregory L; Takahashi, Kazue; Nagy, Laura E

    2011-10-14

    Chronic, heavy alcohol exposure results in inflammation in adipose tissue, insulin resistance, and liver injury. Here we have identified a CYP2E1/Bid/C1q-dependent pathway that is activated in response to chronic ethanol and is required for the development of inflammation in adipose tissue. Ethanol feeding for 25 days to wild-type (C57BL/6J) mice increased expression of multiple markers of adipose tissue inflammation relative to pair-fed controls independent of increased body weight or adipocyte size. Ethanol feeding increased the expression of CYP2E1 in adipocytes, but not stromal vascular cells, in adipose tissue and Cyp2e1(-/-) mice were protected from adipose tissue inflammation in response to ethanol. Ethanol feeding also increased the number of TUNEL-positive nuclei in adipose tissue of wild-type mice but not in Cyp2e1(-/-) or Bid (-/-) mice. Apoptosis contributed to adipose inflammation, as the expression of multiple inflammatory markers was decreased in mice lacking the Bid-dependent apoptotic pathway. The complement protein C1q binds to apoptotic cells, facilitating their clearance and activating complement. Making use of C1q-deficient mice, we found that activation of complement via C1q provided the critical link between CYP2E1/Bid-dependent apoptosis and onset of adipose tissue inflammation in response to chronic ethanol. In summary, chronic ethanol increases CYP2E1 activity in adipose, leading to Bid-mediated apoptosis and activation of complement via C1q, finally resulting in adipose tissue inflammation. Taken together, these data identify a novel mechanism for the development of adipose tissue inflammation that likely contributes to the pathophysiological effects of ethanol.

  8. Obesity-induced chronic inflammation in high fat diet challenged C57BL/6J mice is associated with acceleration of age-dependent renal amyloidosis

    OpenAIRE

    Heijden, R.A. van der; Bijzet, J.; Meijers, W.C.; Yakala, G.K.; Kleemann, R.; Nguyen, T.Q.; Boer, R.A. de; Schalkwijk, C.G.; Hazenberg, B.P.C.; Tietge, U.J.F.; Heeringa, P.

    2015-01-01

    Obesity-induced inflammation presumably accelerates the development of chronic kidney diseases. However, little is known about the sequence of these inflammatory events and their contribution to renal pathology. We investigated the effects of obesity on the evolution of age-dependent renal complications in mice in conjunction with the development of renal and systemic low-grade inflammation (LGI). C57BL/6J mice susceptible to develop age-dependent sclerotic pathologies with amyloid features i...

  9. Chronic inflammation in benign prostate tissue is associated with high-grade prostate cancer in the placebo arm of the Prostate Cancer Prevention Trial*

    Science.gov (United States)

    Gurel, Bora; Lucia, M. Scott; Thompson, Ian M.; Goodman, Phyllis J.; Tangen, Catherine M.; Kristal, Alan R.; Parnes, Howard L.; Hoque, Ashraful; Lippman, Scott M.; Sutcliffe, Siobhan; Peskoe, Sarah B.; Drake, Charles G.; Nelson, William G.; De Marzo, Angelo M.; Platz, Elizabeth A.

    2014-01-01

    Background Chronic inflammation is hypothesized to influence prostate cancer development, although a definitive link has not been established. Methods Prostate cancer cases (N=191) detected on a for-cause (clinically indicated) or end-of-study (protocol directed) biopsy, and frequency-matched controls (N=209), defined as negative for cancer on an end-of-study biopsy, were sampled from the placebo arm of the Prostate Cancer Prevention Trial. Inflammation prevalence and extent in benign areas of biopsy cores were visually assessed using digital images of H&E stained sections. Logistic regression was used to estimate associations. Results 86.2% of cases and 78.2% of controls had at least one biopsy core (of 3 assessed) with inflammation in benign areas, most of which was chronic. Men who had at least one biopsy core with inflammation had 1.78 (95% CI 1.04–3.06) times the odds of prostate cancer compared with men who had zero cores with inflammation. The association was stronger for high-grade disease (Gleason sum 7–10, N=94; odds ratio [OR]=2.24, 95% CI 1.06–4.71). These patterns were present when restricting to cases and controls in whom intraprostatic inflammation was the least likely to have influenced biopsy recommendation because their PSA was low (Inflammation, most of which was chronic, was common in benign prostate tissue, and was positively associated with prostate cancer, especially high-grade. The association did not appear to be due to detection bias. Impact This study supports an etiologic link between inflammation and prostate carcinogenesis, and suggests an avenue for prevention by mitigating intraprostatic inflammation. PMID:24748218

  10. Long-term azithromycin ameliorates not only airway inflammation but also remodeling in a murine model of chronic asthma.

    Science.gov (United States)

    Kang, Ji Young; Jo, Mi Ran; Kang, Hyeon Hui; Kim, Sung Kyoung; Kim, Myoung Sook; Kim, Yong Hyun; Kim, Seok Chan; Kwon, Soon Seog; Lee, Sook Young; Kim, Jin Woo

    2016-02-01

    We investigated the effect of long-term treatment with azithromycin on the pathogenesis of chronic asthma with airway remodeling. Six-week-old-BALB/c mice were sensitized with ovalbumin (OVA) combined with lipopolysaccharide (LPS) for 1 month, then challenged with OVA for 3 months. Azithromycin at 75 mg/kg was administered via oral gavage five times a week during the challenge period. Inflammatory cells, T helper 2 cytokines in bronchoalveolar lavage fluid (BAL) fluid, and airway hyperresponsiveness (AHR) were measured. Parameters related to airway remodeling were evaluated. The levels of neutrophil elastase, Interleukin (IL)-8, and BRP-39 (human homologue YKL-40) were assessed. The expression of MAPK and NF-κB signaling were investigated. Long-term treatment with azithromycin improved AHR and airway inflammation compared with the OVA and the OVA/LPS groups. The concentrations of IL-5 and IL-13 in the OVA/LPS group decreased significantly after azithromycin administration. The levels of neutrophil elastase and IL-8, as surrogate markers of neutrophil activation, were reduced in the azithromycin group compared with the OVA/LPS group. Goblet cell hyperplasia and the smooth muscle thickening of airway remodeling were attenuated after azithromycin treatment. The expression of MAPK/NF-kappaB signal and the level of BRP-39 in the lung decreased remarkably in the OVA/LPS with azithromycin-treated group. This study suggests that in a murine model of chronic asthma, long-term azithromycin treatment ameliorates not only airway inflammation but also airway remodeling by influencing on neutrophilc-related mediators, BRP-39 and MAPK/NF-κB signal pathways. Macrolide therapy might be an effective adjuvant therapy in a chronic, severe asthma with remodeling airway. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Investigating depression-like and metabolic parameters in a chronic low-grade inflammation model

    DEFF Research Database (Denmark)

    Fischer, C. W.; Elfving, B.; Lund, S.

    2012-01-01

    that elevated markers of inflammation predict a poor response to treatment. Furthermore, increasing evidences show that metabolic abnormalities such as obesity and diabetes mellitus type 2 are associated with a low-grade inflammation. Objectives: The aim of this study is to investigate the effects of a systemic...... levels of pro-inflammatory cytokines (TNF-alpha, IL-1, IL-6) together with the expression of enzymes involved in the tryptophan-kynurenine pathway, will be analyzed in specific brain regions using real-time qPCR. Body weight and food intake was measured once a week, while fasting glucose and insulin...... sensitivity was assessed after four weeks of LPS administration. Findings and conclusion: Our results showed that a low dose of LPS increased immobility in the FST relative to vehicle treatment, indicative of depression-like behavior. We did not find any difference in body weight, fasting glucose and insulin...

  12. Low-grade inflammation may moderate the effect of behavioral treatment for chronic pain in adults.

    Science.gov (United States)

    Lasselin, Julie; Kemani, Mike K; Kanstrup, Marie; Olsson, Gunnar L; Axelsson, John; Andreasson, Anna; Lekander, Mats; Wicksell, Rikard K

    2016-10-01

    The purpose of the present pilot study was to explore the moderating role of basal inflammation on the effects of behavioral pain treatment in 41 patients with long-standing pain. Baseline pro-inflammatory status moderated behavioral treatment outcomes: higher pre-treatment levels of Tumor Necrosis Factor (TNF)-α and Interleukin (IL)-6 were related to less improvement in pain intensity, psychological inflexibility and in mental health-related quality of life. The treatment outcomes improved in the subgroup that had low levels of pro-inflammatory cytokines at baseline, while the subjects with higher pro-inflammatory status did not. Altogether, results indicate that low-grade inflammation may influence the behavioral treatment outcomes and provide a possible explanation of the heterogeneity in treatment response.

  13. Is Systemic Inflammation Associated With Elevated PSA Serum Levels In Patients Submitted Chronic Hemodialysis?

    Directory of Open Access Journals (Sweden)

    Gilmar Pereira Silva

    2017-09-01

    Full Text Available Backgroundː whereas that systemic inflammation (SI affects 40–60% of patients on hemodialysis (HD is characterized by serum C-reactive protein (CRP level elevation or proinflammatory interleukin production or both. We evaluated the association between SI and total (tPSA and free PSA (fPSA in patients on HD with tPSA 6 months. Patients were excluded if they had local infections or SI. Hs-CRP was measured using turbidimetry, and tPSA and fPSA levels using immunochemoluminescence. Overall, 27 patients had inflammation (hs-CRP >5 mg/L and 33 had no inflammation (hs-CRP was ≤5 mg/L. In the control group, hs-CRP was ≤ 1 mg/L. Resultsː there was no significant difference in mean levels among groups 3 and 4 for age (p=0,058, tPSA (p=0,74 and fPSA (p=0,30. The SI did not promote differences between groups 1, 2 and 4 for the levels of tPSA (0,71 ± 0,18  vs   0,67 ± 0,15  vs  0,67 ± 0,11; p=0,69 and fPSA (0,34  ±  0,01  vs  0,34  ±  0,01  vs   0,35  ±  0,01, p= 0,59 . As well as maintained no correlation with tPSA and fPSA (p>0,05. Conclusionː The systemic inflammation in hemodialytic patients without clinically detectable cancer (PSA<4ng/ml is no associated with changes fractions of tPSA and fPSA.

  14. Zonulin, inflammation and iron status in patients with early stages of chronic kidney disease

    OpenAIRE

    Lukaszyk, Ewelina; Lukaszyk, Mateusz; Koc-Zorawska, Ewa; Bodzenta-Lukaszyk, Anna; Malyszko, Jolanta

    2017-01-01

    Background/aims Zonulin is the only known regulator of intestinal permeability. It is also considered as a potential inflammatory marker in several conditions such as diabetes and inflammatory bowel syndrome. The aim of the study was to investigate zonulin levels in patients with early stages of CKD and its possible correlation with inflammation, anemia and iron status parameters. Methods Eighty-eight patients with early stages of CKD and 23 healthy volunteers were enrolled in the study. Zonu...

  15. High amylose resistant starch diet ameliorates oxidative stress, inflammation, and progression of chronic kidney disease.

    Directory of Open Access Journals (Sweden)

    Nosratola D Vaziri

    Full Text Available Inflammation is a major mediator of CKD progression and is partly driven by altered gut microbiome and intestinal barrier disruption, events which are caused by: urea influx in the intestine resulting in dominance of urease-possessing bacteria; disruption of epithelial barrier by urea-derived ammonia leading to endotoxemia and bacterial translocation; and restriction of potassium-rich fruits and vegetables which are common sources of fermentable fiber. Restriction of these foods leads to depletion of bacteria that convert indigestible carbohydrates to short chain fatty acids which are important nutrients for colonocytes and regulatory T lymphocytes. We hypothesized that a high resistant starch diet attenuates CKD progression. Male Sprague Dawley rats were fed a chow containing 0.7% adenine for 2 weeks to induce CKD. Rats were then fed diets supplemented with amylopectin (low-fiber control or high fermentable fiber (amylose maize resistant starch, HAM-RS2 for 3 weeks. CKD rats consuming low fiber diet exhibited reduced creatinine clearance, interstitial fibrosis, inflammation, tubular damage, activation of NFkB, upregulation of pro-inflammatory, pro-oxidant, and pro-fibrotic molecules; impaired Nrf2 activity, down-regulation of antioxidant enzymes, and disruption of colonic epithelial tight junction. The high resistant starch diet significantly attenuated these abnormalities. Thus high resistant starch diet retards CKD progression and attenuates oxidative stress and inflammation in rats. Future studies are needed to explore the impact of HAM-RS2 in CKD patients.

  16. Zonulin, inflammation and iron status in patients with early stages of chronic kidney disease.

    Science.gov (United States)

    Lukaszyk, Ewelina; Lukaszyk, Mateusz; Koc-Zorawska, Ewa; Bodzenta-Lukaszyk, Anna; Malyszko, Jolanta

    2018-01-01

    Zonulin is the only known regulator of intestinal permeability. It is also considered as a potential inflammatory marker in several conditions such as diabetes and inflammatory bowel syndrome. The aim of the study was to investigate zonulin levels in patients with early stages of CKD and its possible correlation with inflammation, anemia and iron status parameters. Eighty-eight patients with early stages of CKD and 23 healthy volunteers were enrolled in the study. Zonulin, hepcidin-25, soluble transferrin receptor, interleukin-6 and high-sensitivity C-reactive protein were measured using commercially available assays. Zonulin was significantly lower among patients with CKD in comparison with healthy volunteers. There were no statistically significant differences in zonulin concentration between patients with and without inflammation. Zonulin was significantly correlated with hepcidin only in patients with inflammation. Zonulin was neither related to iron nor related to ferritin. Zonulin cannot be considered as an inflammatory marker in CKD. It does not play a role in the disturbances of iron metabolism in CKD. Its physiological role remains to be elucidated.

  17. Perspectives on chronic inflammation in essential thrombocythemia, polycythemia vera, and myelofibrosis

    DEFF Research Database (Denmark)

    Hasselbalch, Hans K

    2012-01-01

    The morbidity and mortality of patients with the chronic Philadelphia-negative myeloproliferative neoplasms (MPNs), essential thrombocythemia, polycythemia vera, and primary myelofibrosis are mainly caused by cardiovascular diseases, thrombohemorrhagic complications, and bone marrow failure because...

  18. Anti-inflammatory effect of Man-Pen-Fang, a Chinese herbal compound, on chronic pelvic inflammation in rats.

    Science.gov (United States)

    Zhang, Li-Jun; Zhu, Jian-Yong; Sun, Meng-Yao; Song, Ya-Nan; Rahman, Khalid; Peng, Cheng; Zhang, Miao; Ye, Yu-Mei; Zhang, Hong

    2017-08-17

    Traditional Chinese Medicine (TCM) has become the focus of research for the treatment of chronic pelvic inflammatory disease (CPID) based on unique medical theory system. Man-Pen-Fang (MPF), a Chinese herbal compound, which is composed of Thlaspi arvense L. (Cruciferae), Gleditsia sinensis Lam. (Leguminosae), Smilax china L. (Liliaceae), Euonymus alatus (Thunb.) Sieb. (Celastraceae) and Vaccaria segetalis (Neck.) (Caryophyllaceae) MPF has been used for the treatment of CPID and exerted significant clinical curative effects. However, the corresponding active principles and anti-inflammatory mechanism of MPF are still unknown. The objective of present study is to evaluate the effect of MPF on CPID in the chronic pelvic inflammation (CPI) rat model and elucidate its possible anti-inflammatory mechanism. The CPI in rats was induced by administration with E. coli, Staphylococcus aureus and Beta-hemolytic streptococcus. MPF (8.112g/(kg d) (20 times of adult dosage), 4.056g/(kg d) (10 times of adult dosage) and 2.028g/(kg d) (5 times of adult dosage)) and Jingangteng Capsule 2g/(kg d) (20 times of adult dosage) were administered orally for 20 days. The serum levels of five inflammation-associated cytokines (IL-2, IL-6, IL-10, TNF-α and TGF-β 1 ) were determined by enzyme-linked immunoassay, and the mRNA expression levels of TGF-β 1 , P53, Fas, FasL and MMP-2 in the uterus tissue were measured by quantitative RT-PCR. Furthermore, the expression of NF-κB p65 in uterus and ovary tissues was detected by immunohistochemistry assay and the pathological changes induced in the uterus and ovary tissues were observed by histology. MPF caused a reduction in serum levels of IL-2, IL-6, IL-10, TNF-α and TGF-β 1 . The expression of P53 mRNA, Fas/FasL mRNA and MMP-2 mRNA in the uterus tissue was significantly elevated after treating with MPF, in contrast the expression of TGF-β 1 mRNA was decreased. Furthermore, the expression of NF-κB p65 in uterus and ovary tissue was

  19. Effects of inhaled corticosteroids on airway inflammation in chronic obstructive pulmonary disease: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Jen R

    2012-09-01

    Full Text Available Rachel Jen,1 Stephen,1 Rennard,2 Don D Sin1,31Department of Medicine, Respiratory Division, University of British Columbia, Vancouver, BC, Canada; 2Internal Medicine Section of Pulmonary and Critical Care, Nebraska Medical Center, Omaha, NE, USA; 3Institute of Heart and Lung Health and the UBC James Hogg Research Center, St Paul's Hospital, Vancouver, BC, CanadaBackground: Chronic obstructive pulmonary disease (COPD is characterized by chronic inflammation in the small airways. The effect of inhaled corticosteroids (ICS on lung inflammation in COPD remains uncertain. We sought to determine the effects of ICS on inflammatory indices in bronchial biopsies and bronchoalveolar lavage fluid of patients with COPD.Methods: We searched Medline, Embase, Cinahl, and the Cochrane database for randomized, controlled clinical trials that used bronchial biopsies and bronchoalveolar lavage to evaluate the effects of ICS in stable COPD. For each chosen study, we calculated the mean differences in the concentrations of inflammatory cells before and after treatment in both intervention and control groups. These values were then converted into standardized mean differences (SMD to accommodate the differences in patient selection, clinical treatment, and biochemical procedures that were employed across the original studies. If significant heterogeneity was present (P < 0.1, then a random effects model was used to pool the original data; otherwise, a fixed effects model was used.Results: We identified eight original studies that met the inclusion criteria. Four studies used bronchial biopsies (n = 102 participants and showed that ICS were effective in reducing CD4 and CD8 cell counts (SMD, −0.52 units and −0.66 units, 95% confidence interval. The five studies used bronchoalveolar lavage fluid (n = 309, which together showed that ICS reduced neutrophil and lymphocyte counts (SMD, −0.64 units and −0.64 units, 95% confidence interval. ICS on the other hand

  20. Omics-Based Approach Reveals Complement-Mediated Inflammation in Chronic Lymphocytic Inflammation With Pontine Perivascular Enhancement Responsive to Steroids (CLIPPERS

    Directory of Open Access Journals (Sweden)

    Morten Blaabjerg

    2018-04-01

    Full Text Available ObjectiveChronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS is a rare syndrome with relapsing brainstem/cerebellar symptoms. To examine the pathogenic processes and investigate potential biomarkers, we analyzed combined materials of brain and cerebrospinal fluid (CSF by comprehensive methodologies.Materials and methodsTo identify major pathways of perivascular inflammation in CLIPPERS, we first compared the CSF proteome (n = 5 to a neurodegenerative condition, Alzheimer’s disease (AD, n = 5. Activation of complement was confirmed by immunohistochemistry (IHC on CLIPPERS brain samples (n = 3 and by ELISA in the CSF. For potential biomarkers, we used biomarker arrays, and compared inflammatory and vessel-associated proteins in the CSF of CLIPPERS (n = 5 with another inflammatory relapsing CNS disease, multiple sclerosis (RMS, n = 9 and healthy subjects (HS, n = 7.ResultsTwo hundred and seven proteins in the CSF discriminated CLIPPERS from AD. The complement cascade, immunoglobulins, and matrix proteins were among the most frequently represented pathways. Pathway analysis of upstream regulators suggested the importance of vascular cell adhesion protein 1 (VCAM1, IFN-γ, interleukin (IL-1, and IL-10. Differential regulation of more than 10 complement proteins of the 3 complement pathways in the CSF pointed to the role of complement activation. IHC on brain samples confirmed the perivascular complement activation, i.e., deposition of C3bc, C3d, and the terminal C5b-9 complement complex that partially overlapped with accumulation of IgG in the vessel wall. Besides endothelial cell damage, reactivity to smooth muscle actin was lost in the walls of inflamed vessels, but the glia limitans was preserved. The semi-quantitative array indicated that increased level of IL-8/CXCL8 (p < 0.05, eotaxin/CCL11 (p < 0.01, and granulocyte colony-stimulating factor (p < 0.05 in

  1. The Biomarker GlycA Is Associated with Chronic Inflammation and Predicts Long-Term Risk of Severe Infection.

    Science.gov (United States)

    Ritchie, Scott C; Würtz, Peter; Nath, Artika P; Abraham, Gad; Havulinna, Aki S; Fearnley, Liam G; Sarin, Antti-Pekka; Kangas, Antti J; Soininen, Pasi; Aalto, Kristiina; Seppälä, Ilkka; Raitoharju, Emma; Salmi, Marko; Maksimow, Mikael; Männistö, Satu; Kähönen, Mika; Juonala, Markus; Ripatti, Samuli; Lehtimäki, Terho; Jalkanen, Sirpa; Perola, Markus; Raitakari, Olli; Salomaa, Veikko; Ala-Korpela, Mika; Kettunen, Johannes; Inouye, Michael

    2015-10-28

    The biomarker glycoprotein acetylation (GlycA) has been shown to predict risk of cardiovascular disease and all-cause mortality. Here, we characterize biological processes associated with GlycA by leveraging population-based omics data and health records from >10,000 individuals. Our analyses show that GlycA levels are chronic within individuals for up to a decade. In apparently healthy individuals, elevated GlycA corresponded to elevation of myriad inflammatory cytokines, as well as a gene coexpression network indicative of increased neutrophil activity, suggesting that individuals with high GlycA may be in a state of chronic inflammatory response. Accordingly, analysis of infection-related hospitalization and death records showed that increased GlycA increased long-term risk of severe non-localized and respiratory infections, particularly septicaemia and pneumonia. In total, our work demonstrates that GlycA is a biomarker for chronic inflammation, neutrophil activity, and risk of future severe infection. It also illustrates the utility of leveraging multi-layered omics data and health records to elucidate the molecular and cellular processes associated with biomarkers. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. [The role of stress-induced chronic subclinical inflammation in the pathogenesis of the chronic pelvic pain syndrome IIIB in men].

    Science.gov (United States)

    Shormanov, I S; Mozhaev, I I; Sokolova, Kh A; Solovev, A S

    2017-12-01

    This literature review of recent clinical and experimental studies describes the role of oxidative stress in the multifactorial and interdisciplinary pathogenesis of non-inflammatory chronic pelvic pain syndrome IIIB (CPPS-IIIB) in men. The authors outline general biological nature of oxidative stress and its mechanisms. More detailed information is presented on cytokine-mediated chronic subclinical inflammation, one of the key mechanisms of oxidative stress, which is currently being actively studied. It is shown that the imbalance between pro- and anti-inflammatory cytokines observed in patients with CPPS-IIIB can explain some features of the clinical course (in particular, the characteristics of the pain syndrome) and the progression of this disease. In this regard, cytokine profiling of prostatic secretion can provide valuable diagnostic, prognostic and monitoring information in the management of this category of patients. Recently published evidence has demonstrated the essential role of the cytokine-mediated chronic inflammatory response as a mechanism of oxidative stress in the pathogenesis of CPPS-IIIB. Further studies in this area are warranted and in the long term may become a basis for the development of new effective pathogenetic pharmacotherapy of CPPS-IIIB.

  3. Are PTH levels related to oxidative stress and inflammation in chronic kidney disease patients on hemodialysis?

    Science.gov (United States)

    Jaqueto, Marcel; Delfino, Vinicius Daher Alvares; Bortolasci, Chiara Cristina; Barbosa, Decio Sabbatini; Morimoto, Helena Kaminami; Frange, Raquel Ferreira Nassar; Ferreira, Larissa França Fontoura; Guimarães, Fernanda Burle Dos Santos

    2016-01-01

    Patients at end stage renal disease have higher levels of inflammation and oxidative stress than the general population. Many factors contribute to these issues, and the parathyroid hormone (PTH) is also implicated. The study was conducted in order to assess the relationship between PTH levels and inflammation and oxidative stress in hemodialysis patients. Cross-sectional study with patients of two hemodialysis facilities in Londrina, Brazil. Patients with other conditions known to generate oxidative stress and inflammation were excluded. Blood levels of PTH and biochemical parameters of inflammation (interleukins 1 and 6, tumor necrosis factor-alpha) and oxidative stress (total plasma antioxidant capacity, malonic dialdehyde, lipid hydroperoxidation, advanced oxidation protein products, quantification of nitric oxide metabolites, and 8-isoprostane) were measured before a dialysis session. Then, we made correlation analyses between PTH levels - either as the continuous variable or categorized into tertiles-, and inflammatory and oxidative stress biomarkers. PTH did not show any correlation with the tested inflammation and oxidative stress parameters, nor as continuous variable neither as categorical variable. In this descriptive study, the results suggest that the inflammation and oxidative stress of hemodialysis patients probably arise from mechanisms other than secondary hyperparathyroidism. Pacientes com doença renal em estágio terminal têm níveis de inflamação e estresse oxidativo maiores do que a população geral. Muitos fatores contribuem para isso, e o hormônio paratireoidiano (PTH) é um deles. Estudo foi realizado para avaliar a relação entre os níveis de PTH e níveis de inflamação e estresse oxidativo em pacientes em hemodiálise. estudo transversal com pacientes de duas unidades de hemodiálise de Londrina, Brasil. Pacientes com condições causadoras de inflamação e estresse oxidativo foram exclusos. Níveis plasmáticos de PTH e par

  4. The Relationship of Histologically Diagnosed Chronic Prostatic Inflammation and Lower Urinary Tract Symptoms

    Directory of Open Access Journals (Sweden)

    Sebahattin Albayrak

    2014-03-01

    Full Text Available Aim: To evaluate the relationship between pre-biopsy PSA levels, International Prostate Symptom Score (IPSS, maximum urinary flow rate (Qmax, prostate volume and positive core numbers of histologically proved chronic prostatitis in the patients whom underwent transrectal ultrasound guided biopsy for elevated prostate specific antigen (PSA levels. Material and Method: Between January 2012 and 2014, 152 patients underwent TRUS biopsy. Their medical records are examined retrospectively. The mean age of the patients were 62 (45-75. The pathologic specimens were evaluated for the number of cores with chronic prostatitis and percentage of prostatitis. Pre-biopsy levels of PSA, IPSS, maximum urinary flow rate, prostate volume are compared with the number positive cores for chronic prostatitis and their percentages. These variables also compared in the non-chronic prostatitis patients. Results: There was no statistically significant correlation between the positive number of cores for chronic prostatitis and age (P=0.5, r=0.055, a positive correlation was observed between IPSS (P

  5. Dyslipidemia and chronic inflammation markers are correlated with telomere length shortening in Cushing's syndrome.

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    Anna Aulinas

    Full Text Available Cushing's syndrome (CS increases cardiovascular risk (CVR and adipocytokine imbalance, associated with an increased inflammatory state. Telomere length (TL shortening is a novel CVR marker, associated with inflammation biomarkers. We hypothesized that inflammatory state and higher CVR in CS might be related to TL shortening, as observed in premature aging.To evaluate relationships between TL, CVR and inflammation markers in CS.In a cross-sectional study, 77 patients with CS (14 males, 59 pituitary-, 17 adrenal- and 1 ectopic-origin; 21 active disease and 77 age-, gender-, smoking-matched controls were included. Total white blood cell TL was measured by TRF-Southern technique. Clinical data and blood samples were collected (lipids, adrenal function, glucose. Adiponectin, interleukin-6 (IL6 and C-reactive protein (CRP were available in a subgroup of patients (n=32. Correlations between TL and clinical features were examined and multiple linear regression analysis was performed to investigate potential predictors of TL.Dyslipidemic CS had shorter TL than non-dyslipidemic subjects (7328±1274 vs 7957±1137 bp, p<0.05. After adjustment for age and body mass index, cured and active CS dyslipidemic patients had shorter TL than non-dyslipidemic CS (cured: 7187±1309 vs 7868±1104; active: 7203±1262 vs 8615±1056, respectively, p<0.05. Total cholesterol and triglycerides negatively correlated with TL (r-0.279 and -0.259, respectively, p<0.05, as well as CRP and IL6 (r-0.412 and -0.441, respectively, p<0.05. No difference in TL according the presence of other individual CVR factors (hypertension, diabetes mellitus, obesity were observed in CS or in the control group. Additional TL shortening was observed in dyslipidemic obese patients who were also hypertensive, compared to those with two or less CVR factors (6956±1280 vs 7860±1180, respectively, p<0.001. Age and dyslipidemia were independent negative predictors of TL.TL is shortened in dyslipidemic CS

  6. Mechanisms of gastric emptying disturbances in chronic and acute inflammation of the distal gastrointestinal tract

    DEFF Research Database (Denmark)

    Keller, Jutta; Beglinger, Christoph; Holst, Jens Juul

    2009-01-01

    It is unclear why patients with inflammation of the distal bowel complain of symptoms referable to the upper gastrointestinal tract, specifically to gastric emptying (GE) disturbances. Thus we aimed to determine occurrence and putative pathomechanisms of gastric motor disorders in such patients...... and correlated with GE parameters. Results were given in means +/- SD. Compared with CON, GE half time (T) was prolonged by 50% in CD (115 +/- 55 vs. 182 +/- 95 min, P = 0.037). Six CD, 2 DIV, and 2 UC patients had pathological T (>200 min). Postprandial plasma glucose was increased in all patients...

  7. The differences of eosinophil- and neutrophil-related inflammation in elderly allergic and non-allergic chronic obstructive pulmonary disease.

    Science.gov (United States)

    Tsai, Jaw-Ji; Liao, En-Chih; Hsu, Jeng-Yuan; Lee, Wen-Jane; Lai, Yiu-Kay

    2010-11-01

    Chronic obstructive pulmonary disease (COPD) is a common disease in the elderly population and is characterized by airway inflammation. Whether it is a progressive condition resulting from allergic inflammation or a distinct condition involving a pathogen-induced reaction remains unclear. To determine the role of allergic inflammation in the pathogenesis of elderly COPD. A total of 63 elderly adults (21 mite-allergic COPD patients, 29 non-allergic COPD patients, and 13 normal controls) were recruited in this study. The serum-specific IgE for mites, level of interleukin-5 (IL-5), IL-8, leptin, adiponectin, regulated upon activation normal T cell expressed and secreted (RANTES), growth-related oncogene-α (GRO-α), vitamin E, and glutathione (GSH) were determined. The serum levels of GRO-α in patients with COPD were higher in comparison to normal controls (105.8 ± 32.7 vs. 7.5 ± 7.5 pg/mL, p= .021). Compared to patients with non-allergic COPD, patients with mite allergies had a higher serum level of IL-8 (63.2 ± 12.6 vs. 35.0 ± 8.2 pg/mL, p= .022). Although both IL-5 and RANTES levels were increased in COPD patients, there were no significant differences between allergic and non-allergic COPD. There were also no differences in serum levels of leptin, adiponectin, vitamin E, and GSH between COPD patients and normal controls. The increased serum levels of GRO-α indicate that it may have potential as a candidate biomarker for elderly COPD patients. There was no difference of eosinophils-related chemokines in allergic and non-allergic COPD. These results indicated that both adipokines and eosinophil-related chemokines only play trivial roles in the pathogenesis of COPD.

  8. Diagnostic validation and prognostic significance of the Malnutrition-Inflammation Score in nondialyzed chronic kidney disease patients.

    Science.gov (United States)

    Amparo, Fernanda C; Kamimura, Maria A; Molnar, Miklos Z; Cuppari, Lilian; Lindholm, Bengt; Amodeo, Celso; Carrero, Juan J; Cordeiro, Antonio C

    2015-05-01

    Malnutrition and inflammation are highly prevalent and intimately linked conditions in chronic kidney disease (CKD) patients that lead to a state of protein-energy wasting (PEW), the severity of which can be assessed by the Malnutrition-Inflammation Score (MIS). Here, we applied MIS and validated, for the first time, its ability to grade PEW and predict mortality in nondialyzed CKD patients. We cross-sectionally evaluated 300 CKD stages 3-5 patients [median age 61 (53-68) years; estimated glomerular filtration rate 18 (12-27) mL/min/1.73 m(2); 63% men] referred for the first time to our center. Patients were followed during a median 30 (18-37) months for all-cause mortality. A worsening in MIS scale was associated with inflammatory biomarkers increase (i.e. alpha-1 acid glycoprotein, fibrinogen, ferritin and C-reactive protein) as well as a progressive deterioration in various MIS-independent indicators of nutritional status based on anthropometrics, dynamometry, urea kinetics and bioelectric impedance analysis. A structural equation model with two latent variables (assessing simultaneously malnutrition and inflammation factors) demonstrated good fit to the observed data. During a follow-up, 71 deaths were recorded; patients with higher MIS were at increased mortality risk in both crude and adjusted Cox models. MIS appears to be a useful tool to assess PEW in nondialyzed CKD patients. In addition, MIS identified patients at increased mortality risk. © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  9. Effects of active smoking on airway and systemic inflammation profiles in patients with chronic obstructive pulmonary disease.

    Science.gov (United States)

    Pelegrino, Nilva R G; Tanni, Suzana E; Amaral, Renata A F; Angeleli, Aparecida Y O; Correa, Camila; Godoy, Irma

    2013-06-01

    The markers that characterize local and systemic inflammation in chronic obstructive pulmonary disease (COPD) remain unclear, as do their correlations with smoking status and presence of disease. The aim of this study was to assess markers of inflammation in the peripheral blood and airways of current smokers without COPD, of current smokers with COPD and of ex-smokers with COPD. In this study, 17 current smokers with COPD (mean age: 58.2 ± 9.6 years; mean forced expiratory volume in 1 second [FEV1]: 56.1 ± 15.9%), 35 ex-smokers with COPD (mean age: 66.3 ± 7.3 years; mean FEV1: 47.9 ± 17.2%) and 20 current smokers without COPD (mean age: 49.1 ± 6.2 years; mean FEV1: 106.5 ± 15.8%) were evaluated. Spirometry findings, body composition and serum/induced sputum concentrations of tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-8 and IL-10, together with serum C-reactive protein (CRP) levels, were assessed. Serum TNF-α concentration was higher in all current smokers than in ex-smokers with COPD. In current smokers without COPD, serum CRP level was lower than in ex-smokers with COPD and significantly lower than in current smokers with COPD. Sputum TNF-α concentration was higher in current and ex-smokers with COPD than in current smokers without COPD. Multiple regression analyses showed that serum TNF-α was associated with active smoking, and serum CRP and sputum TNF-α were associated with COPD diagnosis. Smoking is associated with higher systemic inflammation in patients with COPD. Current findings also support the hypothesis that smoking and COPD have different effects on the regulation of airway and systemic inflammatory processes.

  10. Prophylactic liraglutide treatment prevents amyloid plaque deposition, chronic inflammation and memory impairment in APP/PS1 mice.

    Science.gov (United States)

    McClean, Paula L; Jalewa, Jaishree; Hölscher, Christian

    2015-10-15

    Type 2 diabetes is a risk factor for Alzheimer's disease (AD). Previously, we have shown that the diabetes drug liraglutide is protective in middle aged and in old APP/PS1 mice. Here, we show that liraglutide has prophylactic properties. When injecting liraglutide once-daily ip. in two months old mice for 8 months, the main hallmarks of AD were much reduced. Memory formation in object recognition and Morris water maze were normalised and synapse loss and the loss of synaptic plasticity was prevented. In addition, amyloid plaque load, including dense core congophilic plaques, was much reduced. Chronic inflammation (activated microglia) was also reduced in the cortex, and neurogenesis was enhanced in the dentate gyrus. The results demonstrate that liraglutide may protect from progressive neurodegeneration that develops in AD. The drug is currently in clinical trials in patients with AD. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Vaccination promotes TH1-like inflammation and survival in chronic Pseudomonas aeruginosa pneumonia. A new prophylactic principle

    DEFF Research Database (Denmark)

    Johansen, H K; Cryz, S J; Hougen, H P

    1997-01-01

    of the macroscopic lung inflammation compared to the other vaccination groups (p = 0.009). The same effect could be obtained by IFN-gamma treatment (p = 0.004). The chronic P. aeruginosa lung infection was established in two inbred mice strains C3H/HeN, known as TH1 responders, and Balb/c, known as TH2 responders...... A stimulated spleen cells from C3H/HeN mice contained three times higher IFN-gamma concentration but only half as high interleukin-4 concentration than those of Balb/c mice. These findings suggest that change from the TH2-like response seen in CF patients towards a TH1 response might improve their prognosis....

  12. Systemic inflammation in peripheral arterial disease with or without coexistent chronic obstructive pulmonary disease: analysis of selected markers.

    Science.gov (United States)

    Wozniak, Krzysztof; Sleszycka, Justyna; Safianowska, Aleksandra; Wiechno, Wieslaw; Domagala-Kulawik, Joanna

    2012-07-04

    Low-grade systemic inflammation plays an important role in the pathogenesis and natural history of chronic obstructive pulmonary disease (COPD) and peripheral arterial disease (PAD). The aim of the study was to analyze plasma concentrations of selected markers of inflammation in patients suffering from PAD with or without coexistent COPD. Thirty patients (6 women) with advanced PAD (at least IIb stage according to Fontaine scale) hospitalized due to critical limb ischemia were examined. In all patients spirometry was performed to confirm or exclude COPD. Plasma concentration of IL-6, IL-8 and TNF-α was measured using ELISA method. Statistical analysis was performed according to COPD status and according to smoking status independently. In the whole group of patients with PAD, COPD was recognized in 14 cases (for the first time in 10 cases). All patients were smokers (46.7% current, 53.3% ex-smokers). We found a significant correlation between FEV1%N (percent of norm of first second expiratory volume) and the number of years of smoking (r = -0.39; p diseases.

  13. Developmental origins of chronic inflammation: a review of the relationship between birth weight and C-reactive protein.

    Science.gov (United States)

    deRosset, Leslie; Strutz, Kelly L

    2015-07-01

    The developmental origins of adult disease hypothesis suggests that the intrauterine environment may program postnatal health outcomes through mechanisms such as chronic inflammation. The purpose of this article was to review the literature on the association between infant birth weight and C-reactive protein (CRP), markers of the fetal environment and inflammation, respectively. We used PubMed, Google Scholar, Web of Science, ScienceDirect, the citation lists of the reviewed literature, and recommendations from experts in the field to identify potential articles. Inclusion criteria for the studies, regardless of study design, included human subjects, documented or self-reported infant birth weight, and a minimum of one measurement of CRP (during childhood, adolescence, or adulthood). Several studies demonstrated a statistically significant inverse association between birth weight and CRP in adulthood, although in many cases only after controlling for markers of current adiposity. No studies significantly linked birth weight to CRP in childhood or adolescence. Longitudinal studies, including multigenerational studies, are needed to further understand whether adult CRP has origins in the fetal environment. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Harnessing Neutrophil Survival Mechanisms during Chronic Infection by Pseudomonas aeruginosa: Novel Therapeutic Targets to Dampen Inflammation in Cystic Fibrosis

    Directory of Open Access Journals (Sweden)

    Benoît S. Marteyn

    2017-06-01

    Full Text Available More than two decades after cloning the cystic fibrosis transmembrane regulator (CFTR gene, the defective gene in cystic fibrosis (CF, we still do not understand how dysfunction of this ion channel causes lung disease and the tremendous neutrophil burden which persists within the airways; nor why chronic colonization by Pseudomonas aeruginosa develops in CF patients who are thought to be immunocompetent. It appears that the microenvironment within the lung of CF patients provides favorable conditions for both P. aeruginosa colonization and neutrophil survival. In this context, the ability of bacteria to induce hypoxia, which in turn affects neutrophil survival is an additional level of complexity that needs to be accounted for when controlling neutrophil fate in CF. Recent studies have underscored the importance of neutrophils in innate immunity and their functions appear to extend far beyond their well-described role in antibacterial defense. Perhaps a disturbance in neutrophil reprogramming during the course of an infection severely modulates the inflammatory response in CF. Furthermore there is an emerging concept that the CFTR itself may be an immune modulator and stimulating CFTR function in CF patients could promote neutrophil and macrophages antimicrobial function. Fostering the resolution of inflammation by favoring neutrophil apoptosis could preserve their microbicidal activities but decrease their proinflammatory potential. In this context, triggering neutrophil apoptosis with roscovitine may be a potential therapeutic option and this is currently being evaluated in CF patients. In the present review we discuss how neutrophils functions are disturbed in CF and how this may relate to chronic infection with P. aeuginosa and we propose novel research directions aimed at modulating neutrophil survival, dampening lung inflammation and ultimately leading to an amelioration of the lung disease.

  15. Mechanisms of virus immune evasion lead to development from chronic inflammation to cancer formation associated with human papillomavirus infection.

    Science.gov (United States)

    Senba, Masachika; Mori, Naoki

    2012-10-02

    Human papillomavirus (HPV) has developed strategies to escape eradication by innate and adaptive immunity. Immune response evasion has been considered an important aspect of HPV persistence, which is the main contributing factor leading to HPV-related cancers. HPV-induced cancers expressing viral oncogenes E6 and E7 are potentially recognized by the immune system. The major histocompatibility complex (MHC) class I molecules are patrolled by natural killer cells and CD8+ cytotoxic T lymphocytes, respectively. This system of recognition is a main target for the strategies of immune evasion deployed by viruses. The viral immune evasion proteins constitute useful tools to block defined stages of the MHC class I presentation pathway, and in this way HPV avoids the host immune response. The long latency period from initial infection to persistence signifies that HPV evolves mechanisms to escape the immune response. It has now been established that there are oncogenic mechanisms by which E7 binds to and degrades tumor suppressor Rb, while E6 binds to and inactivates tumor suppressor p53. Therefore, interaction of p53 and pRb proteins can give rise to an increased immortalization and genomic instability. Overexpression of NF-κB in cervical and penile cancers suggests that NF-κB activation is a key modulator in driving chronic inflammation to cancer. HPV oncogene-mediated suppression of NF-κB activity contributes to HPV escape from the immune system. This review focuses on the diverse mechanisms of the virus immune evasion with HPV that leads to chronic inflammation and cancer.

  16. CS2164, a novel multi-target inhibitor against tumor angiogenesis, mitosis and chronic inflammation with anti-tumor potency.

    Science.gov (United States)

    Zhou, You; Shan, Song; Li, Zhi-Bin; Xin, Li-Jun; Pan, De-Si; Yang, Qian-Jiao; Liu, Ying-Ping; Yue, Xu-Peng; Liu, Xiao-Rong; Gao, Ji-Zhou; Zhang, Jin-Wen; Ning, Zhi-Qiang; Lu, Xian-Ping

    2017-03-01

    Although inhibitors targeting tumor angiogenic pathway have provided improvement for clinical treatment in patients with various solid tumors, the still very limited anti-cancer efficacy and acquired drug resistance demand new agents that may offer better clinical benefits. In the effort to find a small molecule potentially targeting several key pathways for tumor development, we designed, discovered and evaluated a novel multi-kinase inhibitor, CS2164. CS2164 inhibited the angiogenesis-related kinases (VEGFR2, VEGFR1, VEGFR3, PDGFRα and c-Kit), mitosis-related kinase Aurora B and chronic inflammation-related kinase CSF-1R in a high potency manner with the IC 50 at a single-digit nanomolar range. Consequently, CS2164 displayed anti-angiogenic activities through suppression of VEGFR/PDGFR phosphorylation, inhibition of ligand-dependent cell proliferation and capillary tube formation, and prevention of vasculature formation in tumor tissues. CS2164 also showed induction of G2/M cell cycle arrest and suppression of cell proliferation in tumor tissues through the inhibition of Aurora B-mediated H3 phosphorylation. Furthermore, CS2164 demonstrated the inhibitory effect on CSF-1R phosphorylation that led to the suppression of ligand-stimulated monocyte-to-macrophage differentiation and reduced CSF-1R + cells in tumor tissues. The in vivo animal efficacy studies revealed that CS2164 induced remarkable regression or complete inhibition of tumor growth at well-tolerated oral doses in several human tumor xenograft models. Collectively, these results indicate that CS2164 is a highly selective multi-kinase inhibitor with potent anti-tumor activities against tumor angiogenesis, mitosis and chronic inflammation, which may provide the rationale for further clinical assessment of CS2164 as a therapeutic agent in the treatment of cancer. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  17. Evaluation of therapeutic sublingual vaccines in a murine model of chronic house dust mite allergic airway inflammation.

    Science.gov (United States)

    Tourdot, S; Airouche, S; Berjont, N; Da Silveira, A; Mascarell, L; Jacquet, A; Caplier, L; Langelot, M; Baron-Bodo, V; Moingeon, P

    2011-12-01

    Second generation therapeutic vaccines based upon recombinant allergens or natural extracts, potentially formulated in vector systems or adjuvants, are being developed. To this aim, preclinical studies in relevant animal models are needed to select proper allergens, formulations and administration schemes. To develop a chronic house dust mite (HDM) allergy model to evaluate sublingual therapeutic vaccine candidates. The BABL/c mice that were used were sensitized with Dermatophagoides pteronyssinus (Dpte) and Dermatophagoides farinae (Dfar) mite extracts by intraperitoneal injections followed by aerosol exposures. Animals subsequently underwent sublingual immunotherapy (SLIT) with either Dpte, Dfar or Dpte/Dfar extracts, twice a week for 8 weeks. SLIT efficacy was assessed by whole body plethysmography, lung histology and broncho-alveolar lavages cell counts. Specific T cell and antibody responses to major and minor HDM allergens were monitored in tissues and serum/saliva, respectively. Mice sensitized to Dpte and Dfar allergens exhibited strong airway hyperresponsiveness (AHR) and lung inflammatory infiltrates including eosinophils. Sensitized animals mounted Th2-biased cellular and humoral responses specific for group 1 and 2 major allergens, as well as group 5, 7 and 10 minor allergens. This phenotype was sustained for at least 2 months, allowing the evaluation of immunotherapeutic protocols with HDM extracts-based vaccines. In this model, SLIT decreased AHR and Th2 responses and induced HDM-specific IgAs in saliva. The Dpte/Dfar mix proved the most efficacious when compared to Dpte or Dfar extracts alone. The efficacy of a sublingual vaccine based on a Dpte/Dfar allergen extract mix was demonstrated in a well standardized murine model of chronic allergic airway inflammation based on clinically relevant mite allergens. The latter will be used as a benchmark for evaluation of future vaccines, including recombinant allergens. This HDM allergic airway inflammation

  18. Mechanisms of virus immune evasion lead to development from chronic inflammation to cancer formation associated with human papillomavirus infection

    Directory of Open Access Journals (Sweden)

    Masachika Senba

    2012-10-01

    Full Text Available Human papillomavirus (HPV has developed strategies to escape eradication by innate and adaptive immunity. Immune response evasion has been considered an important aspect of HPV persistence, which is the main contributing factor leading to HPV-related cancers. HPV-induced cancers expressing viral oncogenes E6 and E7 are potentially recognized by the immune system. The major histocompatibility complex (MHC class I molecules are patrolled by natural killer cells and CD8+ cytotoxic T lymphocytes, respectively. This system of recognition is a main target for the strategies of immune evasion deployed by viruses. The viral immune evasion proteins constitute useful tools to block defined stages of the MHC class I presentation pathway, and in this way HPV avoids the host immune response. The long latency period from initial infection to persistence signifies that HPV evolves mechanisms to escape the immune response. It has now been established that there are oncogenic mechanisms by which E7 binds to and degrades tumor suppressor Rb, while E6 binds to and inactivates tumor suppressor p53. Therefore, interaction of p53 and pRb proteins can give rise to an increased immortalization and genomic instability. Overexpression of NF-kB in cervical and penile cancers suggests that NF-kB activation is a key modulator in driving chronic inflammation to cancer. HPV oncogene-mediated suppression of NF-kB activity contributes to HPV escape from the immune system. This review focuses on the diverse mechanisms of the virus immune evasion with HPV that leads to chronic inflammation and cancer.

  19. Vaccination promotes TH1-like inflammation and survival in chronic Pseudomonas aeruginosa pneumonia in rats

    DEFF Research Database (Denmark)

    Johansen, H K; Hougen, H P; Cryz, S J

    1995-01-01

    In a rat model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis (CF) we studied whether the inflammatory response could be altered by vaccination. Rats were immunized with either a depolymerized alginate toxin A conjugate (D-ALG toxin A), purified alginate, an O-polysacc...

  20. Increased serum adipokines implicate chronic inflammation in the pathogenesis of overactive bladder syndrome refractory to antimuscarinic therapy.

    Directory of Open Access Journals (Sweden)

    Hsin-Tzu Liu

    Full Text Available OBJECTIVES: Recent studies have shown that chronic inflammation is involved in overactive bladder (OAB syndrome. OAB could be a subtype of neurogenic inflammation. This pilot study investigated serum adipokine levels in patients with OAB refractory to antimuscarinic therapy. METHODS: Thirty consecutive patients with OAB-dry (n = 16 or OAB-wet (n = 14 refractory to previous antimuscarinic treatment were prospectively enrolled in this study, a group of 26 normal subjects without lower urinary tract symptoms served as controls. Concentrations of serum C-reactive protein (CRP, nerve growth factor (NGF, and adipokines including interleukins ([IL], IL-1β, IL-6, IL-8, tumor necrosis factor (TNF-α, monocyte chemotactic protein (MCP-1, insulin, and leptin were quantified using a bead-based human serum adipokine panel B kit. Data were analyzed using the LX 200 platform. Patients were further classified as having dry or wet OAB and having medical diseases or not. The serum CRP, NGF, and adipokine levels were compared between OAB patients and the controls, and between OAB subgroups. RESULTS: The serum concentrations of CRP, NGF, IL-1β, IL-6, IL-8, and TNF-α in OAB-dry and OAB-wet patients were significantly higher than among the controls. There was no significant difference in adipokine levels between OAB-dry and OAB-wet, or between OAB patients with and without medical diseases. Serum CRP and NGF levels were significantly higher only in OAB-wet or OAB patients with medical diseases than among controls. The MCP-1 levels, on the other hand, were significantly higher in OAB-dry or OAB patients with disease, than the controls. CONCLUSIONS: Both OAB-dry and OAB-wet patients showed increased serum CRP, NGF, and adipokine levels compared with the controls, suggesting chronic inflammation of the bladder involving both peripheral and central mechanisms in all OAB patients refractory to antimuscarinic therapy. The increased serum adipokine levels were

  1. Synergistic effects of celecoxib and bupropion in a model of chronic inflammation-related depression in mice.

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    Izaque S Maciel

    Full Text Available This study was aimed to characterize the depression-like behaviour in the classical model of chronic inflammation induced by Complete Freund's Adjuvant (CFA. Male Swiss mice received an intraplantar (i.pl. injection of CFA (50 µl/paw or vehicle. Behavioural and inflammatory responses were measured at different time-points (1 to 4 weeks, and different pharmacological tools were tested. The brain levels of IL-1β and BDNF, or COX-2 expression were also determined. CFA elicited a time-dependent edema formation and mechanical allodynia, which was accompanied by a significant increase in the immobility time in the tail suspension (TST or forced-swimming (FST depression tests. Repeated administration of the antidepressants imipramine (10 mg/kg, fluoxetine (20 mg/kg and bupropion (30 mg/kg significantly reversed depression-like behaviour induced by CFA. Predictably, the anti-inflammatory drugs dexamethasone (0.5 mg/kg, indomethacin (10 mg/kg and celecoxib (30 mg/kg markedly reduced CFA-induced edema. The oral treatment with the analgesic drugs dipyrone (30 and 300 mg/kg or pregabalin (30 mg/kg significantly reversed the mechanical allodyinia induced by CFA. Otherwise, either dipyrone or pregabalin (both 30 mg/kg did not significantly affect the paw edema or the depressive-like behaviour induced by CFA, whereas the oral treatment with dipyrone (300 mg/kg was able to reduce the immobility time in TST. Noteworthy, CFA-induced edema was reduced by bupropion (30 mg/kg, and depression behaviour was prevented by celecoxib (30 mg/kg. The co-treatment with bupropion and celecoxib (3 mg/kg each significantly inhibited both inflammation and depression elicited by CFA. The same combined treatment reduced the brain levels of IL-1β, as well as COX-2 immunopositivity, whilst it failed to affect the reduction of BDNF levels. We provide novel evidence on the relationship between chronic inflammation and depression, suggesting that combination of antidepressant and

  2. Sub-chronic lung inflammation after airway exposures to Bacillus thuringiensis biopesticides in mice

    DEFF Research Database (Denmark)

    Barfod, Kenneth K; Poulsen, Steen Seier; Hammer, Maria

    2010-01-01

    The aim of the present study was to assess possible health effects of airway exposures to Bacillus thuringiensis (Bt) based biopesticides in mice. Endpoints were lung inflammation evaluated by presence of inflammatory cells in bronchoalveolar lavage fluid (BALF), clearance of bacteria from the lung...... lumen and histological alterations of the lungs. Hazard identifications of the biopesticides were carried out using intratracheal (i.t.) instillation, followed by an inhalation study. The two commercial biopesticides used were based on the Bt. subspecies kurstaki and israelensis, respectively. Groups...... of BALB/c mice were i.t instilled with one bolus (3.5 × 105 or 3.4 × 106 colony forming units (CFU) per mouse) of either biopesticide. Control mice were instilled with sterile water. BALFs were collected and the inflammatory cells were counted and differentiated. The BALFs were also subjected to CFU...

  3. Exercise, inflammation, and fatigue in cancer survivors

    OpenAIRE

    LaVoy, Emily C.P.; Fagundes, Christopher P.; Dantzer, Robert

    2016-01-01

    Cancer-related fatigue significantly disrupts normal functioning and quality of life for a substantial portion of cancer survivors, and may persist for years following cancer treatment. While the causes of persistent fatigue among cancer survivors are not yet fully understood, accumulating evidence suggests that several pathways, including chronic inflammation, autonomic imbalance, HPA-axis dysfunction, and/or mitochondrial damage, could contribute towards the disruption of normal neuronal fu...

  4. Serum markers of inflammation and oxidative stress in chronic opium (Taryak) smokers.

    Science.gov (United States)

    Ghazavi, Ali; Mosayebi, Ghasem; Solhi, Hassan; Rafiei, Mohammad; Moazzeni, Seyed Mohammad

    2013-06-01

    A relationship between the expression of inflammation markers, oxidative stress and opium use has not been clearly established. This study was done to determine serum high-sensitivity C-reactive protein (hs-CRP), quantity of C3 and C4 complement factors, immunoglobulins, nitric oxide (NO) and total antioxidant capacity (TAC) in opium smokers and non-drug-using control participants. The present study was done on 44 male opium smokers and 44 controls of the same sex and age (20-40 years). The control group was healthy individuals with no lifetime history of drug abuse or dependence. All of the opium abusers were selected from those who had a history of opium use, for at least one year, with a daily opium dosage not less than 2g. Addicts known to abuse alcohol or other drugs were excluded. Serum hs-CRP concentration was measured using ELISA method and serum C3, C4 and immunoglobulins concentration were determined by Single Radial Immunodiffusion (SRID) method. NO production was estimated through Griess reaction and TAC was assessed by Ferric Reducing/Antioxidant Power (FRAP) test. Serum hs-CRP, complement factors (C3 and C4) and FRAP levels were significantly higher in the opium smokers (8.93 ± 1.93; 138.47 ± 13.39; 68.79 ± 7.02 and 972.75 ± 11.55, respectively) relative to the control group (0.72 ± 0.09; 93.36 ± 8.73; 33.08 ± 7.39 and 761.95 ± 18.61, respectively). These results permit us to conclude that opium smokers indeed present with a low to moderate grade inflammation, which is defined by an increase in acute phase proteins. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Association of Neutrophil-to-Lymphocyte Ratio With Inflammation and Erythropoietin Resistance in Chronic Dialysis Patients

    Directory of Open Access Journals (Sweden)

    Jérôme Pineault

    2017-11-01

    Full Text Available Background: Neutrophil-to-lymphocyte ratio (NLR was widely studied as a prognostic marker in various medical and surgical specialties, but its significance in nephrology is not yet established. Objective: We evaluated its accuracy as an inflammation biomarker in a dialysis population. Design setting: Single-center retrospective study. Patients: The records of all 550 patients who were treated with hemodialysis (HD or peritoneal dialysis (PD from September 2008 to March 2011 were included. Measurements: NLR was calculated from the monthly complete blood count. Methods: Association between NLR and markers of inflammation (C-reactive protein [CRP], serum albumin, and erythropoietin resistance index [ERI] was measured using Spearman coefficient. Results: In total, 120 patients were eligible for the correlation analyses. We found a positive correlation between NLR and CRP (all patients: r = 0.45, P < .001; HD: r = 0.47, P < .001; PD: r = 0.48, P = .13. NLR and albumin were inversely correlated ( r = −0.51, P < .001. Finally, high NLR was associated with a nonsignificant increased ERI, but we have not demonstrated a direct correlation. Limitations: CRP and albumin are not measured routinely and were ordered for a specific clinical reason leading to an indication bias. Also, no relationship with clinical outcome was established. Conclusions: NLR seems to be a good inflammatory biomarker in dialysis in addition to being easily available. However, controlled studies should be conducted to properly assess and validate NLR levels that would be clinically significant and relevant, as well as its prognostic significance and utility in a clinical setting.

  6. Lifestyle and nutritional imbalances associated with Western diseases : causes and consequences of chronic systemic low-grade inflammation in an evolutionary context

    NARCIS (Netherlands)

    Ruiz-Nunez, Begona; Pruimboom, Leo; Dijck-Brouwer, D.A. Janneke; Muskiet, Frits A. J.

    In this review, we focus on lifestyle changes, especially dietary habits, that are at the basis of chronic systemic low grade inflammation, insulin resistance and Western diseases. Our sensitivity to develop insulin resistance traces back to our rapid brain growth in the past 2.5 million years. An

  7. Obesity-induced chronic inflammation in high fat diet challenged C57BL/6J mice is associated with acceleration of age-dependent renal amyloidosis

    NARCIS (Netherlands)

    van der Heijden, Roel A; Bijzet, Johan; Meijers, Wouter C; Yakala, Gopala K; Kleemann, Robert; Nguyen, Tri Q|info:eu-repo/dai/nl/304820482; de Boer, Rudolf A; Schalkwijk, Casper G; Hazenberg, Bouke P C; Tietge, Uwe J F; Heeringa, Peter

    2015-01-01

    Obesity-induced inflammation presumably accelerates the development of chronic kidney diseases. However, little is known about the sequence of these inflammatory events and their contribution to renal pathology. We investigated the effects of obesity on the evolution of age-dependent renal

  8. [Blood cholesterol spectre in patients with acute and chronic inflammation of infectious origin].

    Science.gov (United States)

    Panchyshyn, Iu M; Srokopud, O O; Zhakun, I B; Komarytsia, O I; Huk-Leshnevs'ka, S O; Panchyshyn, M V

    2006-12-01

    Low level of blood cholesterol is often found in patients with diseases which pathogenesis is mainly associated with inflamation. To detect blood cholesterol spectre, 383 patients with acute and chronic infections have been observed, level of blood cholesterol of 1259 patients with different pathology was retrospectively analyzed. It was found that an increase in frequency of low cholesterol and decrease in frequency of high cholesterol in patients with diseases not associated with infections do not depend on the age of patients. Extremely low level of cholesterol (Cholesterol inflamation of infectious origion, oftener in patients with community-acquired pneumonia and chronic virus hepatitis. Patients with intestinal infections have extremely low level of cholesterol; two-fold oftener than healthy persons have.

  9. Lung chitinolytic activity and chitotriosidase are elevated in chronic obstructive pulmonary disease and contribute to lung inflammation.

    Science.gov (United States)

    Létuvé, Séverine; Kozhich, Alexander; Humbles, Alison; Brewah, Yambasu; Dombret, Marie-Christine; Grandsaigne, Martine; Adle, Homa; Kolbeck, Roland; Aubier, Michel; Coyle, Anthony J; Pretolani, Marina

    2010-02-01

    Chronic obstructive pulmonary disease (COPD) is characterized by chronic airway inflammation and emphysematous alveolar destruction. In this study, we have investigated whether chitotriosidase (ChTRase) and acidic mammalian chitinase, two chitinases with chitinolytic activity, are selectively augmented in COPD and contribute to its pathogenesis. We found that smokers with COPD, but not asthmatics, had higher chitinolytic activity and increased levels of ChTRase in bronchoalveolar lavage, more ChTRase-positive cells in bronchial biopsies, and an elevated proportion of alveolar macrophages expressing ChTRase than smokers without COPD or never-smokers. ChTRase accounted for approximately 80% of bronchoalveolar lavage chitinolytic activity, while acidic mammalian chitinase was undetectable. Bronchoalveolar lavage chitinolytic activity and ChTRase were associated with airflow obstruction and emphysema and with the levels of interleukin (IL)-1beta, IL-8, tumor-necrosis factor (TNF)-alpha, and its type II soluble receptor. Tumor necrosis factor-alpha stimulated ChTRase release only from alveolar macrophages from smokers with COPD, and exposure of these cells to ChTRase promoted the release of IL-8, monocyte-chemoattractant protein-1, and metalloproteinase-9. Finally, ChTRase overexpression in the lung of normal mice promoted macrophage recruitment and the synthesis of the murine homologue of IL-8, keratinocyte-derived cytokine, and of monocyte-chemoattractant protein-1. We conclude that pulmonary ChTRase overexpression may represent a novel important mechanism involved in COPD onset and progression.

  10. Investigation of the effect of traditional Chinese medicine on pain and inflammation in chronic nonbacterial prostatitis in rats.

    Science.gov (United States)

    Liu, Y-J; Song, G-H; Liu, G T

    2016-08-01

    According to traditional Chinese medicine, the symptoms of chronic nonbacterial prostatitis/chronic pelvic pain syndrome (CNP/CPPS) may be treated using a cocktail of herbs that stimulate blood circulation ('activating blood circulation formula'). We investigated the effect of three doses of this formula on a rat model of CNP/CPPS. Male Wistar rats were injected with a saline extract of male sex accessory glands on days 0 and 30 to induce prostatitis and then treated daily by gavage between days 32 and 60. Treatment with low, medium and high doses of activating blood circulation formula resulted in an almost total rescue of paw withdrawal threshold at day 60, and treatment with the highest dose also significantly decreased prostate inflammation (assessed histopathologically). We further observed elevated serum prostaglandin E2 levels in the CNP/CPPS model which decreased upon high-dose treatment, and increased Cox-2 expression in the prostate and spinal cord dorsal horn which was rescued in both tissues in the high-dose group and in the prostate in the medium-dose group. These results shed light on a possible mechanism by which activating blood circulation therapy may alleviate pain in a rat model of CNP/CPPS by downregulating Cox-2 expression in the spinal cord, thereby raising the pain threshold. Further research will be needed to fully characterise the mechanism by which activating blood circulation therapy produces this therapeutic effect. © 2016 Blackwell Verlag GmbH.

  11. Effects of four antitussives on airway neurogenic inflammation in a guinea pig model of chronic cough induced by cigarette smoke exposure.

    Science.gov (United States)

    Luo, Yu-long; Li, Pei-bo; Zhang, Chen-chen; Zheng, Yan-fang; Wang, Sheng; Nie, Yi-chu; Zhang, Ke-jian; Su, Wei-wei

    2013-12-01

    The effects of four antitussives, including codeine phosphate (CP), moguisteine, levodropropizine (LVDP) and naringin, on airway neurogenic inflammation and enhanced cough were investigated in guinea pig model of chronic cough. Guinea pigs were exposed to CS for 8 weeks. At the 7th and 8th week, the animals were treated with vehicle, CP (4.8 mg/kg), moguisteine (24 mg/kg), LVDP (14 mg/kg) and naringin (18.4 mg/kg) respectively. Then the cough and the time-enhanced pause area under the curve (Penh-AUC) during capsaicin challenge were recorded. The substance P (SP) content, NK-1 receptor expression and neutral endopeptidase (NEP) activity in lung were determined. Chronic CS exposure induced a bi-phase time course of cough responsiveness to capsaicin. Eight weeks of CS exposure significantly enhanced the airway neurogenic inflammation and cough response in guinea pigs. Two weeks of treatment with CP, moguisteine, LVDP or naringin effectively attenuated the chronic CS-exposure enhanced cough. Only naringin exerted significant effect on inhibiting Penh-AUC, SP content and NK-1 receptor expression, as well as preventing the declining of NEP activity in lung. Chronic CS-exposed guinea pig is suitable for studying chronic pathological cough, in which naringin is effective on inhibiting both airway neurogenic inflammation and enhanced cough.

  12. Hepatic necro-inflammation and elevated liver enzymes: Evaluation with MRI perfusion imaging with gadoxetic acid in chronic hepatitis patients

    International Nuclear Information System (INIS)

    Chen, B.-B.; Hsu, C.-Y.; Yu, C.-W.; Kao, J.-H.; Lee, H.-S.; Liang, P.-C.; Wei, S.-Y.; Hwang, R.-M.; Shih, T.T.-F.

    2014-01-01

    Aim: To evaluate liver necro-inflammation and function by using gadoxetic acid-enhanced dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), with histological analysis as the reference standard. Materials and methods: Seventy-nine subjects (21 healthy subjects; 58 chronic hepatitis patients) who received gadoxetic acid-enhanced DCE-MRI were divided into three subgroups: no (A0, n = 31), mild (A1, n = 27), and moderate–severe (A2–A3, n = 21) activities. Two DCE-MRI models were measured: (1) a dual-input single-compartment model to obtain absolute arterial, portal venous, and total blood flow, arterial fraction (ART), distribution volume, and mean transit time; (2) a curve analysis method to obtain peak, slope, and AUC (area under curve). The serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels also obtained. Statistical testing included Kruskal–Wallis tests for continuous data, Pearson's correlation tests, and multiple linear regression analyses. Results: Hepatic necro-inflammatory activity grades were significantly correlated with fibrotic stages, serum ALT level, ART and AUC. ART was helpful to predict the mild activity (≤A1 versus >A1; Az = 0.728), whereas AUC could differentiate no activity from any activity (A0 versus >A0; Az = 0.703). Peak, slope and AUC were all associated with AST and ALT (p < 0.05). Conclusion: Gadoxetic acid-enhanced DCE-MRI parameters may be used to evaluate the severity of hepatic necro-inflammation and function

  13. Evidence for chronic low-grade systemic inflammation in individuals with agoraphobia from a population-based prospective study.

    Directory of Open Access Journals (Sweden)

    En-Young N Wagner

    Full Text Available Anxiety disorders have been linked to an increased risk of incident coronary heart disease in which inflammation plays a key pathogenic role. To date, no studies have looked at the association between proinflammatory markers and agoraphobia.In a random Swiss population sample of 2890 persons (35-67 years, 53% women, we diagnosed a total of 124 individuals (4.3% with agoraphobia using a validated semi-structured psychiatric interview. We also assessed socioeconomic status, traditional cardiovascular risk factors (i.e., body mass index, hypertension, blood glucose levels, total cholesterol/high-density lipoprotein-cholesterol ratio, and health behaviors (i.e., smoking, alcohol consumption, and physical activity, and other major psychiatric diseases (other anxiety disorders, major depressive disorder, drug dependence which were treated as covariates in linear regression models. Circulating levels of inflammatory markers, statistically controlled for the baseline demographic and health-related measures, were determined at a mean follow-up of 5.5 ± 0.4 years (range 4.7 - 8.5.Individuals with agoraphobia had significantly higher follow-up levels of C-reactive protein (p = 0.007 and tumor-necrosis-factor-α (p = 0.042 as well as lower levels of the cardioprotective marker adiponectin (p = 0.032 than their non-agoraphobic counterparts. Follow-up levels of interleukin (IL-1β and IL-6 did not significantly differ between the two groups.Our results suggest an increase in chronic low-grade inflammation in agoraphobia over time. Such a mechanism might link agoraphobia with an increased risk of atherosclerosis and coronary heart disease, and needs to be tested in longitudinal studies.

  14. The relationship between mean platelet volume and neutrophil/lymphocyte ratio with inflammation and proteinuria in chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Gulay Yilmaz

    2017-01-01

    Full Text Available Atherosclerosis, which develops as a result of inflammation, is the most important cause of morbidity and mortality in chronic kidney disease (CKD. In this study, we investigated the relationship of mean platelet volume (MPV and neutrophil/lymphocyte ratio (NLR with inflammation and proteinuria in patients with CKD Stage 3-4. Healthy individuals who applied to nephrology clinic for checkup purposes acted as controls. Fifty-three patients and 30 healthy controls were included in the study. Patients with diabetes mellitus, active infection, malignancy, and coronary artery disease were excluded from the study. Biochemistry values and hemograms were recorded for all patients and for control group. NLR was calculated. The relationship between MPV/NLR and protein, fibrinogen, and proteinuria was evaluated. Our study showed a statistically significant difference between CKD group and healthy control (HC group in uric acid, fibrinogen, C-reactive protein, and NLR values (P <0.01, P <0.01, P = 0.01, P <0.01, respectively. No statistically significant difference was found between CKD and HC groups for MPV (P = 0.307. Correlation analysis revealed a statistically significant relationship between NLR and creatinine (P <0.00, r = 0.571, uric acid (P <0.00, r = 0.436, glomerular filtration rate (P <0.00, r = −0.418, 24 h urine protein (P = 0.004, r = 0.311, and 24 h urine microalbumin (P = 0.001, r = 0.354. A statistically significant relationship was detected between MPV and platelet count (P <0.001, r = −0.422, age (P = 0.004, r = −0.312, uric acid (P = 0.04, r = −0.226, and fibrinogen (P = 0.023, r = −0.249. Whereas, a statistically significant relationship was detected between NLR and microalbuminuria/proteinuria, there was no statistically significant relationship between MPV and microalbuminuria/proteinuria. Our study showed that the NLR is high in CKD group and is correlated with uric acid and proteinuria, which are known to be associated

  15. Individual serum saturated fatty acids and markers of chronic subclinical inflammation: the Insulin Resistance Atherosclerosis Study.

    Science.gov (United States)

    Santaren, Ingrid D; Watkins, Steven M; Liese, Angela D; Wagenknecht, Lynne E; Rewers, Marian J; Haffner, Steven M; Lorenzo, Carlos; Festa, Andreas; Bazinet, Richard P; Hanley, Anthony J

    2017-11-01

    Recent evidence has documented distinct effects of individual saturated FAs (SFAs) on cardiometabolic outcomes, with potential protective effects from odd- and very long-chain SFAs (VLSFAs). Cross-sectional and prospective associations of individual serum SFAs (12:0, 14:0, 15:0, 16:0, 18:0, 20:0, 22:0, and total SFA) with proinflammatory biomarkers and adiponectin were investigated in 555 adults from the IRAS. Principal component analysis (PCA) of proinflammatory markers yielded three clusters: principal component (PC) 1: fibrinogen, white cell count, C-reactive protein; PC 2: plasminogen activator inhibitor-1 (PAI-1), TNF-α, IL-18; PC 3: IL-6 and IL-8. Cross-sectional analyses on proinflammatory PCs and adiponectin, and prospective analyses on 5 year PAI-1 and fibrinogen concentrations were conducted with multiple regression. Total SFA and 16:0 were positively associated with PC 1 and PC 2, and negatively associated with adiponectin. The 14:0 was positively associated with PC 1 and negatively associated with adiponectin. In contrast, 15:0, 20:0, and 22:0 were negatively associated with PC 2, and 20:0 and 22:0 were positively associated with adiponectin. The 18:0 was negatively associated with PC 3. Prospectively, 15:0, 18:0, 20:0, and 22:0 were negatively associated with 5 year PAI-1 concentrations. The results demonstrate that individual SFAs have distinct roles in subclinical inflammation, highlighting the unique metabolic impacts of individual SFAs. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

  16. Chest radiographs in acquired antibody deficiency syndrome with chronic granulomatous inflammation

    International Nuclear Information System (INIS)

    Qaiyumi, S.A.A.; Peest, D.; Galanski, M.; Medizinische Hochschule Hannover

    1990-01-01

    Ten cases of acquired antibody deficiency syndrome with chronic granulomatous infection were diagnosed in our hospital during the past 10 years. We were able to perform a retrospective analysis of the initial and follow-up chest radiographs in 8 of these patients. The following pathological findings could be demonstrated: 1. increased bronchovascular markings in the basal lung fields, 2. reticular densities in the middle and basal lung fields, 3. confluent nodular densities of varying size in the periphery of the basal and middle fields, 4. pulmonary infiltrates in the middle and lower lobes, 5. hilar node enlargement of moderate extent. Findings 2, 3 and 5 completely disappeared under steroid therapy whereas 1 showed only partial recovery. If both the radiologic and serologic findings are considered, it is possible to differentiate this disease from sarcoidosis. (orig.) [de

  17. From inflammation to cancer.

    Science.gov (United States)

    Korniluk, A; Koper, O; Kemona, H; Dymicka-Piekarska, V

    2017-02-01

    The participation of inflammation in the progression of cancer for many years have been the subject of research. In the 19th century, there was evidence that an acute inflammation may inhibit the development of cancer. However, chronic inflammation affects the progression of the disease. Today, it is known that inflammation and cancer use similar mechanisms of development such as severe cell proliferation or angiogenesis. It has been shown that prolonged presence of inflammatory cells and factors in the tumor microenvironment can accelerate its growth and inhibit apoptosis of transformed cells. In this article we present a brief history of the discovery mechanisms and potential links between acute and chronic inflammation and cancer.

  18. Can inhaled fluticasone alone or in combination with salmeterol reduce systemic inflammation in chronic obstructive pulmonary disease? – study protocol for a randomized controlled trial [NCT00120978

    Directory of Open Access Journals (Sweden)

    Ramesh Warren

    2006-02-01

    Full Text Available Abstract Background Systemic inflammation is associated with various complications in chronic obstructive pulmonary disease including weight loss, cachexia, osteoporosis, cancer and cardiovascular diseases. Inhaled corticosteroids attenuate airway inflammation, reduce exacerbations, and improve mortality in chronic obstructive pulmonary disease. Whether inhaled corticosteroids by themselves or in combination with a long-acting β2-adrenoceptor agonist repress systemic inflammation in chronic obstructive pulmonary disease is unknown. The Advair Biomarkers in COPD (ABC study will determine whether the effects of inhaled corticosteroids alone or in combination with a long-acting β2-adrenoceptor agonist reduce systemic inflammation and improve health status in patients with chronic obstructive pulmonary disease. Methods/Design After a 4-week run-in phase during which patients with stable chronic obstructive pulmonary disease will receive inhaled fluticasone (500 micrograms twice daily, followed by a 4-week withdrawal phase during which all inhaled corticosteroids and long acting β2-adrenoceptor agonists will be discontinued, patients will be randomized to receive fluticasone (500 micrograms twice daily, fluticasone/salmeterol combination (500/50 micrograms twice daily, or placebo for four weeks. The study will recruit 250 patients across 11 centers in western Canada. Patients must be 40 years of age or older with at least 10 pack-year smoking history and have chronic obstructive pulmonary disease defined as forced expiratory volume in one second to vital capacity ratio of 0.70 or less and forced expiratory volume in one second that is 80% of predicted or less. Patients will be excluded if they have any known chronic systemic infections, inflammatory conditions, history of previous solid organ transplantation, myocardial infarction, or cerebrovascular accident within the past 3 months prior to study enrolment. The primary end-point is serum C

  19. Association between Inflammation and Cardiac Geometry in Chronic Kidney Disease: Findings from the CRIC Study.

    Directory of Open Access Journals (Sweden)

    Jayanta Gupta

    Full Text Available Left ventricular hypertrophy (LVH and myocardial contractile dysfunction are independent predictors of mortality in patients with chronic kidney disease (CKD. The association between inflammatory biomarkers and cardiac geometry has not yet been studied in a large cohort of CKD patients with a wide range of kidney function.Plasma levels of interleukin (IL-1β, IL-1 receptor antagonist (IL-1RA, IL-6, tumor necrosis factor (TNF-α, transforming growth factor (TGF-β, high-sensitivity C-Reactive protein (hs-CRP, fibrinogen and serum albumin were measured in 3,939 Chronic Renal Insufficiency Cohort study participants. Echocardiography was performed according to the recommendations of the American Society of Echocardiography and interpreted at a centralized core laboratory.LVH, systolic dysfunction and diastolic dysfunction were present in 52.3%, 11.8% and 76.3% of the study subjects, respectively. In logistic regression analysis adjusted for age, sex, race/ethnicity, diabetic status, current smoking status, systolic blood pressure, urinary albumin- creatinine ratio and estimated glomerular filtration rate, hs-CRP (OR 1.26 [95% CI 1.16, 1.37], p<0.001, IL-1RA (1.23 [1.13, 1.34], p<0.0001, IL-6 (1.25 [1.14, 1.36], p<0.001 and TNF-α (1.14 [1.04, 1.25], p = 0.004 were associated with LVH. The odds for systolic dysfunction were greater for subjects with elevated levels of hs-CRP (1.32 [1.18, 1.48], p<0.001 and IL-6 (1.34 [1.21, 1.49], p<0.001. Only hs-CRP was associated with diastolic dysfunction (1.14 [1.04, 1.26], p = 0.005.In patients with CKD, elevated plasma levels of hs-CRP and IL-6 are associated with LVH and systolic dysfunction.

  20. Obesity-induced chronic inflammation in high fat diet challenged C57BL/6J mice is associated with acceleration of age-dependent renal amyloidosis.

    Science.gov (United States)

    van der Heijden, Roel A; Bijzet, Johan; Meijers, Wouter C; Yakala, Gopala K; Kleemann, Robert; Nguyen, Tri Q; de Boer, Rudolf A; Schalkwijk, Casper G; Hazenberg, Bouke P C; Tietge, Uwe J F; Heeringa, Peter

    2015-11-13

    Obesity-induced inflammation presumably accelerates the development of chronic kidney diseases. However, little is known about the sequence of these inflammatory events and their contribution to renal pathology. We investigated the effects of obesity on the evolution of age-dependent renal complications in mice in conjunction with the development of renal and systemic low-grade inflammation (LGI). C57BL/6J mice susceptible to develop age-dependent sclerotic pathologies with amyloid features in the kidney, were fed low (10% lard) or high-fat diets (45% lard) for 24, 40 and 52 weeks. HFD-feeding induced overt adiposity, altered lipid and insulin homeostasis, increased systemic LGI and adipokine release. HFD-feeding also caused renal upregulation of pro-inflammatory genes, infiltrating macrophages, collagen I protein, increased urinary albumin and NGAL levels. HFD-feeding severely aggravated age-dependent structural changes in the kidney. Remarkably, enhanced amyloid deposition rather than sclerosis was observed. The degree of amyloidosis correlated significantly with body weight. Amyloid deposits stained positive for serum amyloid A (SAA) whose plasma levels were chronically elevated in HFD mice. Our data indicate obesity-induced chronic inflammation as a risk factor for the acceleration of age-dependent renal amyloidosis and functional impairment in mice, and suggest that obesity-enhanced chronic secretion of SAA may be the driving factor behind this process.

  1. Carotenoids, inflammation, and oxidative stress--implications of cellular signaling pathways and relation to chronic disease prevention.

    Science.gov (United States)

    Kaulmann, Anouk; Bohn, Torsten

    2014-11-01

    Several epidemiologic studies have shown that diets rich in fruits and vegetables reduce the risk of developing several chronic diseases, such as type 2 diabetes, atherosclerosis, and cancer. These diseases are linked with systemic, low-grade chronic inflammation. Although controversy persists on the bioactive ingredients, several secondary plant metabolites have been associated with these beneficial health effects. Carotenoids represent the most abundant lipid-soluble phytochemicals, and in vitro and in vivo studies have suggested that they have antioxidant, antiapoptotic, and anti-inflammatory properties. Recently, many of these properties have been linked to the effect of carotenoids on intracellular signaling cascades, thereby influencing gene expression and protein translation. By blocking the translocation of nuclear factor κB to the nucleus, carotenoids are able to interact with the nuclear factor κB pathway and thus inhibit the downstream production of inflammatory cytokines, such as interleukin-8 or prostaglandin E2. Carotenoids can also block oxidative stress by interacting with the nuclear factor erythroid 2-related factor 2 pathway, enhancing its translocation into the nucleus, and activating phase II enzymes and antioxidants, such as glutathione-S-transferases. In this review, which is organized into in vitro, animal, and human investigations, we summarized current knowledge on carotenoids and metabolites with respect to their ability to modulate inflammatory and oxidative stress pathways and discuss potential dose-health relations. Although many pathways involved in the bioactivity of carotenoids have been revealed, future research should be directed toward dose-response relations of carotenoids, their metabolites, and their effect on transcription factors and metabolism. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Chronic rhinosinusitis with nasal polyps is characterized by B-cell inflammation and EBV-induced protein 2 expression

    Science.gov (United States)

    Hulse, Kathryn E.; Norton, James E.; Suh, Lydia; Zhong, Qiu; Mahdavinia, Mahboobeh; Simon, Patrick; Kern, Robert C.; Conley, David B.; Chandra, Rakesh K.; Tan, Bruce K.; Peters, Anju T.; Grammer, Leslie C.; Harris, Kathleen E.; Carter, Roderick G.; Kato, Atsushi; Schleimer, Robert P.

    2013-01-01

    Background Despite the high prevalence and morbidity of chronic rhinosinusitis (CRS), little is known about the mechanisms that underlie its pathogenesis. Recent studies have suggested that B cells might play an important role in CRS. Objective We sought to thoroughly characterize B lineage cells within sinus tissues of patients with CRS and healthy control subjects and to determine whether levels of EBV-induced protein 2, which is known to play an important role in the development of B-cell responses, were increased in patients with CRS. Methods Cells isolated from sinus tissues of patients with CRS and healthy control subjects were characterized by means of flow cytometry and immunohistochemistry. Local production of antibodies was measured in tissue extracts, nasal lavage fluid, and sera by using multiplex bead arrays and ELISA. Quantitative RT-PCR, ELISA, and Western blotting were used to assess gene and protein expression from tissue extracts. Results Nasal polyps (NPs) from patients with CRS had increased levels of both B cells and plasma cells compared with uncinate tissue from healthy control subjects (P < .05). NPs also contained significantly increased levels of several antibody isotypes compared with normal uncinate tissue (P < .05), but no differences in circulating antibody levels were found. Interestingly, levels of EBV-induced protein 2 were also increased in NPs (P < .05) and were positively correlated with expression of plasma cell markers (CD138 and B lymphocyte–induced maturation protein) in sinus tissue. Conclusion B cells and plasma cells are enriched in NPs, actively produce antibodies locally, and might contribute to chronic inflammation in patients with CRS. Elucidating the mechanisms that underlie this excessive local B-cell response might provide novel insights for the development of improved therapeutic strategies. PMID:23473835

  3. Development of asthmatic inflammation in mice following early-life exposure to ambient environmental particulates and chronic allergen challenge

    Directory of Open Access Journals (Sweden)

    Cristan Herbert

    2013-03-01

    Childhood exposure to environmental particulates increases the risk of development of asthma. The underlying mechanisms might include oxidant injury to airway epithelial cells (AEC. We investigated the ability of ambient environmental particulates to contribute to sensitization via the airways, and thus to the pathogenesis of childhood asthma. To do so, we devised a novel model in which weanling BALB/c mice were exposed to both ambient particulate pollutants and ovalbumin for sensitization via the respiratory tract, followed by chronic inhalational challenge with a low mass concentration of the antigen. We also examined whether these particulates caused oxidant injury and activation of AEC in vitro. Furthermore, we assessed the potential benefit of minimizing oxidative stress to AEC through the period of sensitization and challenge by dietary intervention. We found that characteristic features of asthmatic inflammation developed only in animals that received particulates at the same time as respiratory sensitization, and were then chronically challenged with allergen. However, these animals did not develop airway hyper-responsiveness. Ambient particulates induced epithelial injury in vitro, with evidence of oxidative stress and production of both pro-inflammatory cytokines and Th2-promoting cytokines such as IL-33. Treatment of AEC with an antioxidant in vitro inhibited the pro-inflammatory cytokine response to these particulates. Ambient particulates also induced pro-inflammatory cytokine expression following administration to weanling mice. However, early-life dietary supplementation with antioxidants did not prevent the development of an asthmatic inflammatory response in animals that were exposed to particulates, sensitized and challenged. We conclude that injury to airway epithelium by ambient environmental particulates in early life is capable of promoting the development of an asthmatic inflammatory response in sensitized and antigen-challenged mice. These

  4. Alterations in lipid metabolism mediate inflammation, fibrosis, and proliferation in a mouse model of chronic cholestatic liver injury.

    Science.gov (United States)

    Moustafa, Tarek; Fickert, Peter; Magnes, Christoph; Guelly, Christian; Thueringer, Andrea; Frank, Sasa; Kratky, Dagmar; Sattler, Wolfgang; Reicher, Helga; Sinner, Frank; Gumhold, Judith; Silbert, Dagmar; Fauler, Günter; Höfler, Gerald; Lass, Achim; Zechner, Rudolf; Trauner, Michael

    2012-01-01

    The liver controls central processes of lipid and bile acid homeostasis. We aimed to investigate whether alterations in lipid metabolism contribute to the pathogenesis of chronic cholestatic liver disease in mice. We used microarray and metabolic profiling analyses to identify alterations in systemic and hepatic lipid metabolism in mice with disruption of the gene ATP-binding cassette sub-family B member 4 (Abcb4(-/-) mice), a model of inflammation-induced cholestatic liver injury, fibrosis, and cancer. Alterations in Abcb4(-/-) mice, compared with wild-type mice, included deregulation of genes that control lipid synthesis, storage, and oxidation; decreased serum levels of cholesterol and phospholipids; and reduced hepatic long-chain fatty acyl-CoAs (LCA-CoA). Feeding Abcb4(-/-) mice the side chain-modified bile acid 24-norursodeoxycholic acid (norUDCA) reversed their liver injury and fibrosis, increased serum levels of lipids, lowered phospholipase and triglyceride hydrolase activities, and restored hepatic LCA-CoA and triglyceride levels. Additional genetic and nutritional studies indicated that lipid metabolism contributed to chronic cholestatic liver injury; crossing peroxisome proliferator-activated receptor (PPAR)-α-deficient mice with Abcb4(-/-) mice (to create double knockouts) or placing Abcb4(-/-) mice on a high-fat diet protected against liver injury, with features similar to those involved in the response to norUDCA. Placing pregnant Abcb4(-/-) mice on high-fat diets prevented liver injury in their offspring. However, fenofibrate, an activator of PPARα, aggravated liver injury in Abcb4(-/-) mice. Alterations in lipid metabolism contribute to the pathogenesis and progression of cholestatic liver disease in mice. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

  5. Chronic Infection of the Prostate by Chlamydia muridarum Is Accompanied by Local Inflammation and Pelvic Pain Development.

    Science.gov (United States)

    Sanchez, Leonardo R; Breser, Maria L; Godoy, Gloria J; Salazar, Florencia C; Mackern-Oberti, Juan P; Cuffini, Cecilia; Motrich, Ruben D; Rivero, Virginia E

    2017-04-01

    Chlamydia trachomatis urogenital infections are the leading cause of sexually transmitted bacterial infections. Although the prevalence of chlamydial infection is similar in men and women, current research is mainly focused on women, neglecting the study of male genital tract infections. We, therefore, investigated Chlamydia infection in the rodent male genital tract. Male NOD and C57BL/6 mice were inoculated in the meatus urethra with C. muridarum. Bacterial DNA, leukocyte infiltration of male genital tract tissues, pelvic pain, and Chlamydia-specific immune responses were analyzed at different time points. The inoculation of C. muridarum in the meatus urethra of male mice resulted in an ascending and widely disseminated infection of the male genital tract. C. muridarum remained longer and with the highest bacterial burdens in the prostate, thus showing a special tropism for this organ. Infection caused leukocyte infiltration, mainly composed by neutrophils, and also induced early pelvic pain development that rapidly dropped and resolved as the infection became chronic. Bacterial load and leukocyte infiltration was observed in all prostate lobes, although dorsolateral prostate was the most affected lobe. Interestingly, immune responses induced by both mice strains were characterized by the production of high levels of IL-10 during early stages of the infection, with highest and sustained levels observed in NOD mice, which showed to be less efficient in clearing the infection. Chronic infection of the prostate accompanied by local inflammation and pelvic pain development described herein have important implications for the improvement of the diagnosis and for the design of new efficient therapies. Prostate 77:517-529, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  6. Kinetics of chronic inflammation in Nile tilapia fed n‑3 and n‑6 essential fatty acids

    Directory of Open Access Journals (Sweden)

    Róberson Sakabe

    2013-03-01

    Full Text Available The objective of this work was to investigate the effect of dietary supplementation with essential fatty acids on the kinetics of macrophage accumulation and giant cell formation in Nile tilapia (Oreochromis niloticus. The supplementation sources were soybean oil (SO, source of omega 6, n‑6 and linseed oil (LO, source of omega 3, n‑3, in the following proportions: 100% SO; 75% SO + 25% LO; 50% SO + 50% LO; 25% SO + 75% LO; and 100% LO (four replicates per treatment. After a feeding period of three months, growth performance was evaluated, and glass coverslips were implanted into the subcutaneous connective tissue of fish, being removed for examination at 2, 4, 6, and 8 days after implantation. Growth performance did not differ between treatments. Fish fed 100% linseed oil diet had the greatest macrophage accumulation and the fastest Langhans cell formation on the sixth day. On the eighth day, Langhans cells were predominant on the coverslips implanted in the fish feed 75 and 100% linseed oil. n‑3 fatty acids may contribute to macrophage recruitment and giant cell formation in fish chronic inflammatory response to foreign body.

  7. Oral inflammation and infection, and chronic medical diseases: implications for the elderly.

    Science.gov (United States)

    Scannapieco, Frank A; Cantos, Albert

    2016-10-01

    Oral diseases, such as caries and periodontitis, not only have local effects on the dentition and on tooth-supporting tissues but also may impact a number of systemic conditions. Emerging evidence suggests that poor oral health influences the initiation and/or progression of diseases such as atherosclerosis (with sequelae including myocardial infarction and stoke), diabetes mellitus and neurodegenerative diseases (such as Alzheimer's disease, rheumatoid arthritis and others). Aspiration of oropharyngeal (including periodontal) bacteria causes pneumonia, especially in hospitalized patients and the elderly, and may influence the course of chronic obstructive pulmonary disease. This article addresses several pertinent aspects related to the medical implications of periodontal disease in the elderly. There is moderate evidence that improved oral hygiene may help prevent aspiration pneumonia in high-risk patients. For other medical conditions, because of the absence of well-designed randomized clinical trials in elderly patients, no specific guidance can be provided regarding oral hygiene or periodontal interventions that enhance the medical management of older adults. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Ferulic acid inhibits neuro-inflammation in mice exposed to chronic unpredictable mild stress.

    Science.gov (United States)

    Liu, Ya-Min; Shen, Ji-Duo; Xu, Li-Ping; Li, Han-Bing; Li, Yu-Cheng; Yi, Li-Tao

    2017-04-01

    Ferulic acid is a hydroxycinnamic acid that widely presents in plant cell wall components. It has been demonstrated that ferulic acid can attenuate depressive-like behaviors in both forced swimming test and tail suspension test. Considering that depression is an inflammatory related mental disease, our present study was aimed to investigate the role of ferulic acid in the regulation of microglia activation, pro-inflammatory cytokines, nuclear factor kappa B (NF-κB) and nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome in mice exposed to chronic unpredictable mild stress (CUMS). Our results firstly showed that decreased sucrose preference and increased immobility time were completely reversed by administration with ferulic acid and fluoxetine for four weeks. Then, we found that CUMS significantly caused interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) up-regulation, microglia, NF-κB signaling and NLRP3 inflammasome activation in the prefrontal cortex. On the contrary, these activated inflammatory response induced by CUMS were reversed by ferulic acid and fluoxetine as well, suggesting that anti-inflammatory related mechanism was involved in the antidepressant-like effects of ferulic acid in stressed mice. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Suppression of NFAT5-mediated Inflammation and Chronic Arthritis by Novel κB-binding Inhibitors

    Directory of Open Access Journals (Sweden)

    Eun-Jin Han

    2017-04-01

    Full Text Available Nuclear factor of activated T cells 5 (NFAT5 has been implicated in the pathogenesis of various human diseases, including cancer and arthritis. However, therapeutic agents inhibiting NFAT5 activity are currently unavailable. To discover NFAT5 inhibitors, a library of >40,000 chemicals was screened for the suppression of nitric oxide, a direct target regulated by NFAT5 activity, through high-throughput screening. We validated the anti-NFAT5 activity of 198 primary hit compounds using an NFAT5-dependent reporter assay and identified the novel NFAT5 suppressor KRN2, 13-(2-fluoro-benzylberberine, and its derivative KRN5. KRN2 inhibited NFAT5 upregulation in macrophages stimulated with lipopolysaccharide and repressed the formation of NF-κB p65-DNA complexes in the NFAT5 promoter region. Interestingly, KRN2 selectively suppressed the expression of pro-inflammatory genes, including Nos2 and Il6, without hampering high-salt-induced NFAT5 and its target gene expressions. Moreover, KRN2 and KRN5, the latter of which exhibits high oral bioavailability and metabolic stability, ameliorated experimentally induced arthritis in mice without serious adverse effects, decreasing pro-inflammatory cytokine production. Particularly, orally administered KRN5 was stronger in suppressing arthritis than methotrexate, a commonly used anti-rheumatic drug, displaying better potency and safety than its original compound, berberine. Therefore, KRN2 and KRN5 can be potential therapeutic agents in the treatment of chronic arthritis.

  10. Anti-inflammatory activity of four solvent fractions of ethanol extract of Mentha spicata L. investigated on acute and chronic inflammation induced rats.

    Science.gov (United States)

    Arumugam, P; Priya, N Gayatri; Subathra, M; Ramesh, A

    2008-07-01

    Anti-inflammatory effects of four solvent fractions of ethanol extract of Mentha spicata were evaluated in acute and chronic inflammation induced in Wistar albino rats. Lipid peroxidation (LPO) and some antioxidants produced during chronic inflammation were quantitated. Hexane (320mg/kg of body weight in 25% DMSO), chloroform (320mg/kg body weight in 25% DMSO), ethyl acetate (160mg/kg body weight in 25% DMSO), aqueous (320mg/kg of body weight in ddH(2)O) fractions, two negative control groups (25% DMSO and ddH(2)O) and two anti-inflammatory drugs (Diclofenac: 25mg/kg of body weight; Indomethacin: 10mg/kg of body weight both in ddH(2)O) were administered by oral intubations to the eight groups of rats consisting six animals, each. In acute study, 1% carrageenan was injected subcutaneously in the sub-plantar region of the right hind paw after 1h of administration of test doses. The increased paw edema was measured at 0.5, 1, 2, 4, 8, 16 and 24h intervals. In the chronic study, the oral administration was carried out for seven consecutive days. On eighth day, four sterile cotton pellets (50mg each) were implanted subcutaneously in the dorsal region of the rats. On the sixteenth day, the rats were sacrificed and the cotton pellets with granulomatous tissue were dissected out and weighed (fresh and dry). Both in chronic and acute inflammation, ethyl acetate (EAF) and aqueous fraction (AF) were effective. EAF is comparable with the positive standards in chronic inflammation. The results indicate that EAF's anti-inflammatory activity is largely due to its ability to modulate in vivo antioxidants.

  11. Malnutrition-inflammation score is associated with handgrip strength in nondialysis-dependent chronic kidney disease patients.

    Science.gov (United States)

    Amparo, Fernanda C; Cordeiro, Antonio C; Carrero, Juan J; Cuppari, Lilian; Lindholm, Bengt; Amodeo, Celso; Kamimura, Maria A

    2013-07-01

    The malnutrition-inflammation score (MIS) is a nutritional scoring system that has been associated with muscle strength among dialysis patients. We aimed to test whether MIS is able to predict muscle strength in nondialysis-dependent chronic kidney disease (NDD-CKD) individuals. This was a cross-sectional study conducted at the Dante Pazzanese Institute of Cardiology, Hypertension, and Nephrology Division outpatient clinic. We evaluated 190 patients with NDD-CKD stages 2-5 (median 59.5 [interquartile range 51.4-66.9] years; 64% men). MIS was calculated without computing dialysis vintage to the scoring. HGS was assessed in the dominant arm. Anthropometric, laboratory, and body composition parameters were recorded. A strong negative correlation was found between HGS and MIS (r = -0.42; P ≤ .001) in univariate analysis. In multivariate regressions, adjustment for age, sex, diabetes, glomerular filtration rate, body cell mass, and C-reactive protein did not materially diminish these relationships. MIS shares strong links with objective measures of muscle strength in NDD-CKD patients. Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  12. CLINICAL AND LABORATORY ASPECTS OF CHRONIC HEPATITIS B ON THE BACKGROUND OF REFRACTORY ANEMIA OF INFLAMMATION IN CHILDREN OF UZBEKISTAN

    Directory of Open Access Journals (Sweden)

    F. I. Inoyatova

    2017-01-01

    Full Text Available A total of 75 children with chronic hepatitis B (ChHB with a refractory variant of anemia of inflammation (AV course were examined, the pathogenetic manifestation of which was the development of iron overload syndrome (IOS. It was revealed that against the background of an increase in the severity of the IOS, the incidence of progressive forms of the disease with persistent prevalence of asthenovegetative, hemorrhagic syndromes and severe hepatosplenomegaly increased. At the same time, the leading biochemical syndromes were the presence of cytolysis with prolonged hyperfermentemia, endotoxemia and mesenchymal inflammatory syndrome. A directly proportional dependence of the hepcidin-25 peptide level on the degree of expression of the IOS, the higher the presentation of the IOS, the higher the level of suppression of peptide expression in hepatocytes. Diagnostically significant tests of severe forms of IOS in ChHB in children are the presence of hemosiderin in the urine and an increase in the level of sIL-6R in the serum.  

  13. Lamin-B in systemic inflammation, tissue homeostasis, and aging.

    Science.gov (United States)

    Chen, Haiyang; Zheng, Xiaobin; Zheng, Yixian

    2015-01-01

    Gradual loss of tissue function (or homeostasis) is a natural process of aging and is believed to cause many age-associated diseases. In human epidemiology studies, the low-grade and chronic systemic inflammation in elderly has been correlated with the development of aging related pathologies. Although it is suspected that tissue decline is related to systemic inflammation, the cause and consequence of these aging phenomena are poorly understood. By studying the Drosophila fat body and gut, we have uncovered a mechanism by which lamin-B loss in the fat body upon aging induces age-associated systemic inflammation. This chronic inflammation results in the repression of gut local immune response, which in turn leads to the over-proliferation and mis-differentiation of the intestinal stem cells, thereby resulting in gut hyperplasia. Here we discuss the implications and remaining questions in light of our published findings and new observations.

  14. Endostatin in chronic kidney disease: Associations with inflammation, vascular abnormalities, cardiovascular events and survival.

    Science.gov (United States)

    Kanbay, Mehmet; Afsar, Baris; Siriopol, Dimitrie; Unal, Hilmi Umut; Karaman, Murat; Saglam, Mutlu; Gezer, Mustafa; Taş, Ahmet; Eyileten, Tayfun; Guler, Ahmet Kerem; Aydin, İbrahim; Oguz, Yusuf; Tarim, Kayhan; Covic, Adrian; Yilmaz, Mahmut Ilker

    2016-09-01

    Endostatin, generated from collagen XVIII, and endorepellin, possess dual activity as modifiers of both angiogenesis and endothelial cell autophagy. Plasma endostatin levels are elevated in a large number of diseases, and may reflect endothelial cell dysfunction. Few data on endostatins are available for patients with chronic kidney disease (CKD). We tested whether serum endostatin values are predictive for all-cause mortality and cardiovascular events (CVEs) in a CKD population. A total of 519 CKD pre-dialysis patients were included. Baseline plasma endostatin levels were measured in all patients. All included patients were followed-up (time-to-event analysis) until occurrence of death, fatal or nonfatal CVEs. Fatal and nonfatal CVE including death, stroke, and myocardial infarction were recorded prospectively The mean age of the patients was 52.2±12.3years. There were 241 (46.4%) males, 111 (21.4%) had diabetes, 229 (44.1%) were smokers and 103 (19.8%) had a previous CVE. After a median follow-up of 46months, 46 patients died and 172 had a new CVE. In the univariable Cox survival analysis, higher endostatin levels were associated with a higher risk for both outcomes. However, after adjusting for traditional (age, gender, smoking status, diabetes, systolic blood pressure, HDL and total cholesterol) and renal-specific (eGFR, proteinuria and hsCRP) risk factors, endostatin levels remained associated only with the CVE outcome (HR=1.88, 95% CI 1.37-2.41 for a 1 SD increase in log endostatin values). Endostatin levels are independently associated with incident CVE in CKD patients, but show limited prediction abilities for all-cause mortality and CVE above traditional and renal-specific risk factors. Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  15. A Gpr120-selective agonist improves insulin resistance and chronic inflammation in obese mice.

    Science.gov (United States)

    Oh, Da Young; Walenta, Evelyn; Akiyama, Taro E; Lagakos, William S; Lackey, Denise; Pessentheiner, Ariane R; Sasik, Roman; Hah, Nasun; Chi, Tyler J; Cox, Jason M; Powels, Mary Ann; Di Salvo, Jerry; Sinz, Christopher; Watkins, Steven M; Armando, Aaron M; Chung, Heekyung; Evans, Ronald M; Quehenberger, Oswald; McNelis, Joanne; Bogner-Strauss, Juliane G; Olefsky, Jerrold M

    2014-08-01

    It is well known that the ω-3 fatty acids (ω-3-FAs; also known as n-3 fatty acids) can exert potent anti-inflammatory effects. Commonly consumed as fish products, dietary supplements and pharmaceuticals, ω-3-FAs have a number of health benefits ascribed to them, including reduced plasma triglyceride levels, amelioration of atherosclerosis and increased insulin sensitivity. We reported that Gpr120 is the functional receptor for these fatty acids and that ω-3-FAs produce robust anti-inflammatory, insulin-sensitizing effects, both in vivo and in vitro, in a Gpr120-dependent manner. Indeed, genetic variants that predispose to obesity and diabetes have been described in the gene encoding GPR120 in humans (FFAR4). However, the amount of fish oils that would have to be consumed to sustain chronic agonism of Gpr120 is too high to be practical, and, thus, a high-affinity small-molecule Gpr120 agonist would be of potential clinical benefit. Accordingly, Gpr120 is a widely studied drug discovery target within the pharmaceutical industry. Gpr40 is another lipid-sensing G protein-coupled receptor, and it has been difficult to identify compounds with a high degree of selectivity for Gpr120 over Gpr40 (ref. 11). Here we report that a selective high-affinity, orally available, small-molecule Gpr120 agonist (cpdA) exerts potent anti-inflammatory effects on macrophages in vitro and in obese mice in vivo. Gpr120 agonist treatment of high-fat diet-fed obese mice causes improved glucose tolerance, decreased hyperinsulinemia, increased insulin sensitivity and decreased hepatic steatosis. This suggests that Gpr120 agonists could become new insulin-sensitizing drugs for the treatment of type 2 diabetes and other human insulin-resistant states in the future.

  16. CYTOTOXIC LYMPHOCYTES: THE ROLE IN INFLAMMATION IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE EXACERBATION AND REMISSION

    Directory of Open Access Journals (Sweden)

    N. A. Raspopina

    2014-01-01

    Full Text Available Background: Despite the number of publications related to the expression of surface antigens of periphery blood lymphocytes in chronic obstructive pulmonary disease (COPD, algorithm for interpreting of the results and implicating pathogene-tic treatments still needs to be developed. Aim: To assess the role of cytotoxic lymphocytes in the maintaining of inflammation in COPD. Materials and methods: To examine immune status in 37 patients with COPD exacerbation or remission and 24 healthy donors (control group, blood cytotoxic T-lymphocytes and NK-cells contents were measured using indirect immunofluorescence method. Absolute and relative numbers of lymphocytes expressing CD3, CD4, CD8, CD16, CD20, CD23, CD25, CD54, CD71, CD72, HLA-DR, CD95 antigens, membrane immunoglobulins  M (mIgM and G (mIgG were estimated. Results: In COPD, significantly increased numbers of blood cytotoxic lymphocytes were demonstrated independently from the disease stage (p < 0.001. During COPD exacerbation, significant elevations of CD4, CD8, CD20, CD72, NК-cells numbers, serum mIgM and mIgG were demonstrated. During remission, CD20 and CD72 content returned to normal, though, increased numbers of other cytotoxic cells persisted promoting inflammation and progressive damage of pulmonary and bronchial tissues. Conclusion: Observed changes may be due to excessive stimulation of T-cell component of immune system in COPD patients both in exacerbation and remission. Relative reduction of total T-lymphocyte numbers indicates non-specific (non-infectious inflammation type. High cytotoxic potential of immune system results in pulmonary damage and promotes development of pneumosclerosis and emphysema.

  17. Abnormal blood rheology and chronic low grade inflammation: possible risk factors for accelerated atherosclerosis and coronary artery disease in Lewis negative subjects.

    Science.gov (United States)

    Alexy, Tamas; Pais, Eszter; Wenby, Rosalinda B; Mack, Wendy J; Hodis, Howard N; Kono, Naoko; Wang, Jun; Baskurt, Oguz K; Fisher, Timothy C; Meiselman, Herbert J

    2015-03-01

    To test the hypothesis that abnormal hemorheology and chronic low-grade inflammation are more prevalent in Lewis negative individuals, possibly contributing to premature atherosclerosis. We enrolled 223 healthy subjects (154 females, mean age: 64yrs). Conventional risk factors, markers of inflammation and hemorheological profiles were measured; Lewis blood group was determined by serology. Conventional risk factors (age, gender, BMI, blood pressure, lipid profile, smoking habit) did not differ among Lewis phenotypes. However, markers of inflammation (WBC, hs-CRP, ESR) were significantly elevated and rheological parameters (RBC aggregation, plasma viscosity) were abnormal in Lewis negative subjects, especially when compared to the Le(a-b+) group. With a prevalence of 33% in select populations, our data support the hypothesis that Le(a-b-) represents a pro-inflammatory phenotype that may contribute to the elevated cardiovascular risk in this group. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. The effect of n-3 fatty acids and coenzyme Q10 supplementation on neutrophil leukotrienes, mediators of inflammation resolution and myeloperoxidase in chronic kidney disease.

    Science.gov (United States)

    Barden, Anne E; Shinde, Sujata; Burke, Valerie; Puddey, Ian B; Beilin, Lawrence J; Irish, Ashley B; Watts, Gerald F; Mori, Trevor A

    2018-03-22

    Neutrophils release leukotriene (LT)B 4 and myeloperoxidase (MPO) that may be important mediators of chronic inflammation in chronic kidney disease (CKD). The n-3 fatty acids (n-3 FA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have the potential to attenuate inflammation through production of LTB 5 and the Specialized Proresolving Lipid Mediators (SPM) that promote the resolution of inflammation. In animal models, coenzyme Q10 (CoQ) also attenuates inflammation by reducing MPO and LTB 4 . This study evaluated the independent and combined effects of n-3 FA and CoQ supplementation on neutrophil leukotrienes, the pro-inflammatory eicosanoid 5-hydroxyeicosatetraenoic acid (5-HETE), SPM, and plasma MPO, in patients with CKD. In a double-blind, placebo-controlled intervention of factorial design, 85 patients with CKD were randomized to either n-3 FA (4 g), CoQ (200 mg), both supplements, or control (4 g olive oil), daily for 8 weeks. Plasma MPO and calcium ionophore-stimulated neutrophil release of LTs, 5-HETE and SPM were measured at baseline and after 8 weeks. Seventy four patients completed the intervention. n-3 FA, but not CoQ, significantly increased neutrophil LTB 5 (P n-3 FA or CoQ. Plasma MPO was significantly reduced with n-3 FA alone (P = 0.013) but not when given in combination with CoQ. n-3 FA supplementation in patients with CKD leads to increased neutrophil release of LTB 5 and several SPM, as well as a reduction in plasma MPO that may have important implications for limiting chronic inflammation. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Technetium-99m human polyclonal immunoglobulin g studies and conventional bone scans to detect active joint inflammation in chronic rheumatoid arthritis

    International Nuclear Information System (INIS)

    Berna, Ll.; Torres, G.; Estorch, M.; Martinez-Duncker, D.; Carrio, I.; Diez, C.

    1992-01-01

    Rheumatoid arthritis is a chronic polyarthritis in which active inflammed joints coexist with joints in remission. We performed bone scans ( 99m Tc-DPD) and 99m Tc human polyclonal immunoglobulin G scans ( 99m Tc-IgG) in 18 patients with rheumatoid arthritis to assess the uptake in actively inflammed joints and in joints in which remission after inflammation had occurred. A quantitative analysis of tracer uptake in each joint was performed on both scans. In 123 joints without current active inflammation, an increased 99m Tc-DPD uptake was observed (2.31±1.27), whereas no 99m Tc-IgG uptake was noted (1.18±0.32). Some 78 joints with mild pain or swelling exhibited increased 99m Tc-DPD uptake (2.48±1.14) and increased 99m Tc-IgG uptake (1.76±0.50; P 99m Tc-DPD uptake (2.39±0.93) and increased 99m Tc-IgG uptake (1.79±0.51; P 99m Tc-IgG scans distinguish between joints with and without active inflammation in chronic rheumatoid arthritis, whereas bone scans do not. Thus, 99m Tc-IgG scans may be useful in identifying joints with current active inflammation in rheumatoid arthritis. (orig.)

  20. How Self-Reliance Is Understood: Viewpoints from One Local ...

    African Journals Online (AJOL)

    DrNneka

    Tanzania's 1967 policy of self-reliance (Hultin 1985, p.8). Before looking at the way self-reliance is understood in rural Malawi during a process of development, it may be beneficial to look at some of the tensions between micro and macro forms of development. Leading to Self-Reliance. Development Aid is a term that has ...

  1. How self-reliance is understood: viewpoints from one local ...

    African Journals Online (AJOL)

    How self-reliance is understood: viewpoints from one local community in Malawi. ... model that resists dependence on external aid, empowers community development, and provides opportunities to sustain development activity through local initiative, can be employed to increase social capital leading to sustainable growth.

  2. The association of dietary intake and supplementation of specific polyunsaturated fatty acids with inflammation and functional capacity in chronic obstructive pulmonary disease: a systematic review

    OpenAIRE

    Atlantis, Evan; Cochrane, Belinda

    2015-01-01

    ABSTRACT Objective: This systematic review sought to identify the association of dietary intake and supplementation of specific polyunsaturated fatty acids with inflammation and function in people with chronic obstructive pulmonary disease (COPD). Data sources: We searched electronic databases including PubMed, CINAHL, MEDLINE, EMBASE, The Cochrane Library, ProQuest Dissertations and Theses, Scopus, Google Scholar, Trove, and WHO International Clinical Trials Registry Platform and reference l...

  3. Relations of Visceral and Abdominal Subcutaneous Adipose Tissue, Body Mass Index, and Waist Circumference to Serum Concentrations of Parameters of Chronic Inflammation

    Directory of Open Access Journals (Sweden)

    Inga Schlecht

    2016-06-01

    Full Text Available Background: Different measures of body fat composition may vary in their relations to parameters of chronic inflammation. Methods: We assessed the relations of visceral (VAT and subcutaneous adipose tissue (SAT, BMI, and waist circumference (WC to serum concentrations of high-sensitive C-reactive protein (hs-CRP, tumor necrosis factor alpha (TNF-α, interleukin-6 (IL-6, resistin, and adiponectin in 97 healthy adults using multivariate linear regression models, adjusted for age, sex, smoking, physical activity, menopausal status, and use of aspirin or non-steroidal anti-inflammatory drugs (NSAIDs. Parameters of chronic inflammation were mutually adjusted. Results: VAT (β = 0.34, SAT (β = 0.43, BMI (β = 0.40, and WC (β = 0.47 were all significantly associated with hs-CRP. BMI was additionally inversely related to adiponectin (β = -0.29. In exploratory subgroup analyses defined by gender, BMI, smoking, and use of aspirin or NSAIDs, VAT was the strongest indicator for increased levels of IL-6, SAT was the most consistent indicator for increased levels of hs-CRP, and BMI was the most consistent indicator for decreased levels of adiponectin. WC showed to be a weak indicator for increased levels of hs-CRP and decreased levels of adiponectin. Conclusion: VAT, SAT, BMI, and WC show distinct associations with parameters of chronic inflammation. Whether these differences reflect differential metabolic risks requires clarification by longitudinal studies.

  4. Analysis of local chronic inflammatory cell infiltrate combined with systemic inflammation improves prognostication in stage II colon cancer independent of standard clinicopathologic criteria.

    Science.gov (United States)

    Turner, Natalie; Wong, Hui-Li; Templeton, Arnoud; Tripathy, Sagarika; Whiti Rogers, Te; Croxford, Matthew; Jones, Ian; Sinnathamby, Mathuranthakan; Desai, Jayesh; Tie, Jeanne; Bae, Susie; Christie, Michael; Gibbs, Peter; Tran, Ben

    2016-02-01

    In Stage II colon cancer, multiple independent studies have shown that a dense intratumoural immune infiltrate (local inflammation) is associated with improved outcomes, while systemic inflammation, measured by various markers, has been associated with poorer outcomes. However, previous studies have not considered the interaction between local and systemic inflammation, nor have they assessed the type of inflammatory response compared with standard clinicopathologic criteria. In order to evaluate the potential clinical utility of inflammatory markers in Stage II colon cancer, we examined local and systemic inflammation in a consecutive series of patients with resected Stage II colon cancer between 2000 and 2010 who were identified from a prospective clinical database. Increased intratumoural chronic inflammatory cell (CIC) density, as assessed by pathologist review of hematoxylin and eosin stained slides, was used to represent local inflammation. Neutrophil-to-lymphocyte ratio (NLR) >5, as calculated from pre-operative full blood counts, was used to represent systemic inflammation. In 396 eligible patients identified, there was a non-significant inverse relationship between local and systemic inflammation. Increased CIC density was significantly associated with improved overall (HR 0.45, p = 0.001) and recurrence-free survival (HR 0.37, p = 0.003). High NLR was significantly associated with poorer overall survival (HR 2.56, p < 0.001). The combination of these markers further stratified prognosis independent of standard high-risk criteria, with a dominant systemic inflammatory response (low CIC/high NLR) associated with the worst outcome (5-year overall survival 55.8%). With further validation this simple, inexpensive combined inflammatory biomarker might assist in patient selection for adjuvant chemotherapy in Stage II colon cancer. © 2015 UICC.

  5. Simple serum markers for significant liver inflammation in chronic hepatitis B patients with an alanine aminotransferase level lower than 2 times upper limit of normal

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    LI Qiang

    2016-06-01

    Full Text Available ObjectiveTo investigate the simple serum markers for significant liver inflammation in chronic hepatitis B (CHB patients with an alanine aminotransferase (ALT level of <2 times upper limit of normal (ULN. MethodsThe clinical data of 278 CHB patients with ALT <2×ULN (ULN=40 U/L were analyzed retrospectively. Significant liver inflammation was defined as a liver inflammatory activity grade (G ≥2. The t-test was used for comparison of normally distributed continuous data between groups, and the Kruskal-Wallis rank sum test was used for non-normally distributed continuous data; the chi-square test was used for comparison of categorical data between groups. Multivariate logistic regression analysis was used to identify independent predictors for significant liver inflammation in CHB patients with ALT <2×ULN. The receiver operating characteristic (ROC curve was used to evaluate the diagnostic value of serum markers in significant liver inflammation. ResultsOf the 278 CHB patients enrolled, 175 (62.9% had no significant liver inflammation (G0-1 group and 103 (37.1% had significant liver inflammation (G2-4 group. There were significant differences in ALT, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase (GGT, albumin, globulin, prothrombin time (PT, platelet, absolute neutrophil count, hyaluronic acid (HA, glycocholic acid, precollagen Ⅲ, and collagen type Ⅳ(ⅣC between the two groups (all P<0.05. The multivariate regression analysis showed that GGT, PT, ⅣC, and HA were independent predictors for significant liver inflammation in CHB patients with ALT<2×ULN (OR=1.015, 1.600, 1.151, and 1.014, P=0.008, 0.021, 0.003, and 0.018. The areas under the ROC curve for GGT, PT, IVC, and HA to diagnose significant liver inflammation were 0.804, 0.722, 0.707, and 0.632, respectively. The cut-off value of 48.5 U/L for GGT to predict significant liver inflammation had a specificity of 90.3% and a negative

  6. A high-fat, high-protein diet attenuates the negative impact of casein-induced chronic inflammation on testicular steroidogenesis and sperm parameters in adult mice.

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    Zhao, Jing-Lu; Zhao, Yu-Yun; Zhu, Wei-Jie

    2017-10-01

    The interaction between obesity and chronic inflammation has been studied. Diet-induced obesity or chronic inflammation could reduce the testicular functions of males. However, the mechanism underlying the reproductive effects of fattening foods in males with or without chronic inflammation still needs further discussion. This study was aimed to investigate the effects of high-fat, high-protein diet on testicular steroidogenesis and sperm parameters in adult mice under physiological and chronic inflammatory conditions. Because casein can trigger a non-infectious systemic inflammatory response, we used casein injection to induce chronic inflammation in male adult Kunming mice. Twenty-four mice were randomly and equally divided into four groups: (i) normal diet+saline (Control); (ii) normal diet+casein (ND+CS); (iii) high-fat, high-protein diet+saline (HFPD+SI); (iv) high-fat, high-protein diet+casein (HFPD+CS). After 8weeks, there was a significant increase in body weight for groups HFPD+SI and HFPD+CS and a decrease in group ND+CS compared with the control. The serum levels of tumor necrosis factor alpha (TNF-α), interleukin-10 (IL-10) and lipid profiles were increased markedly in groups ND+CS, HFPD+SI and HFPD+CS compared with the control. A remarkable reduction of serum adiponectin level occurred in group HFPD+CS compared with group ND+CS. Sperm parameters (sperm count, viability and abnormality) were also adversely affected in groups ND+CS and HFPD+SI. Groups ND+CS and HFPD+SI showed severe pathological changes in testicular tissues. Semiquantitative RT-PCR, Western blot and immunohistochemical staining also showed significant reductions in both testicular mRNA and protein levels of steroidogenic acute regulatory (StAR) and cytochrome P450scc (CYP11A1) in groups HFPD+SI and HFPD+CS compared with the control, whereas testicular mRNA and protein levels of 3β-hydroxysteroid dehydrogenase (3β-HSD) in groups HFPD+SI and HFPD+CS significantly increased. The m

  7. Dying for love: Perimenopausal degeneration of vaginal microbiome drives the chronic inflammation-malignant transformation of benign prostatic hyperplasia to prostatic adenocarcinoma.

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    Reece, Albert Stuart

    2017-04-01

    Prostatic carcinoma is the second commonest cancer in males and is so common as to become almost holoendemic with advancing age. The recent demonstration that far from being benign, "benign" prostatic hypertrophy is a likely a reaction of the prostate to chronic untreated lower genital tract infection, and that this chronic inflammation is likely the usual precursor to the frequent occurrence of prostatic carcinoma has far reaching implications. The obvious source for the chronic inflammatory stimulus in the prostate is the documented dramatically altered lower female genital microbiota associated with the menopause. Hence the major hypothesis is that prostatic cancer may arise due to chronic infection and inflammation in the prostate gland consequent upon the altered microbiome of the menopausal female genital tract. This has implications for testing and diagnosis, treatment, population health and personal hygiene practices. It suggests that male dyspareunia, although almost never encountered in clinical practice may in fact be relatively common in older males, and in particular if diagnosed, represents a critical opportunity for therapeutic intervention to interrupt the chronic inflammation - cancer transformation and progression which has been well documented in other tissues. It implies that the coordinated application of next generation sequencing to the microbiome of the lower genital tracts of male and female couples, including seminal fluid, will have both research applications to further explore this sequence, as well as finding application as a potential population level screening procedure as is presently done for the "Thin Prep" cervical screening for human papillomavirus in females. Moreover this insight opens up new opportunities for chemointervention and chemoprevention for this important clinicopathological progression. These considerations give rise to the exciting possibility that prostatic malignancy may be preventable by various methods of local

  8. Hepatitis C Virus Nonstructural 3/4A Protein Dampens Inflammation and Contributes to Slow Fibrosis Progression during Chronic Fibrosis In Vivo.

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    Ruchi Bansal

    Full Text Available HCV infection typically induces liver injury and inflammation, which appears to be responsible for the associated fibrogenesis. To date, the mechanism underlying the different rates of disease progression remains unclear. The aim of the study is to understand the possible role of the HCV non-structural (NS 3/4A protein in the fibrosis progression. We used NS3/4A-expressing transgenic mice (NS3/4A-Tg to accomplish the goals of the study. Different stages of liver fibrosis were induced in wild-type and NS3/4A-Tg mice by single carbon tetrachloride (acute or multiple injections for 4 (intermediate or 8 (chronic weeks. Fibrotic parameters, inflammatory responses and hepatocyte turnover were extensively examined. Hepatic expression of HCV NS3/4A did not induce spontaneous liver damage. However, NS3/4A expression exerted contrasting effects during acute and chronic liver damage. During early fibrogenesis and intermediate fibrosis (4 weeks, NS3/4A-Tg mice exhibited enhanced liver damage whereas reduced fibrosis was observed in NS3/4A-Tg during chronic liver fibrosis (8 weeks. Furthermore, attenuated inflammation was observed in NS3/4A-Tg during chronic fibrosis with increase in M2 macrophages, hepatocyte proliferation, decreased hepatocyte apoptosis and decreased ductular reaction. In conclusion, during early fibrogenesis, HCV NS3/4A contributes to liver damage. While, during chronic liver fibrosis, NS3/4A dampens inflammation and induces hepatocyte regeneration thereby contributing to slow fibrosis progression to promote its survival or persistence.

  9. Urachal tumour: case report of a poorly understood carcinoma

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    Vallarino Luigi

    2009-11-01

    Full Text Available Abstract Background Urachal carcinoma is an uncommon neoplasm associated with poor prognosis. Case presentation A 45-year-old man was admitted with complaints of abdominal pain and pollakisuria. A soft mass was palpable under his navel. TC-scan revealed a 11 × 6 cm tumor, which was composed of a cystic lesion arising from the urachus and a solid mass component at the urinary bladder dome. The tumor was removed surgically. Histological examination detected poor-differentiated adenocarcinoma, which had invaded the urinary bladder. The patient has been followed up without recurrence for 6 months. Conclusion The urachus is the embryological remnant of urogenital sinus and allantois. Involution usually happens before birth and urachus is present as a median umbilical ligament. The pathogenesis of urachal tumours is not fully understood. Surgery is the treatment of choice and role of adjuvant treatment is not clearly understood.

  10. Effects of Omega-3 Fatty Acids on Markers of Inflammation in Patients With Chronic Kidney Disease: A Controversial Issue.

    Science.gov (United States)

    Hu, Chun; Yang, Ming; Zhu, Xuejing; Gao, Peng; Yang, Shikun; Han, Yachun; Chen, Xianghui; Xiao, Li; Yuan, Shuguang; Liu, Fuyou; Kanwar, Yashpal S; Sun, Lin

    2018-04-01

    Chronic kidney disease (CKD) is a global problem which contributes to a significant morbidity and mortality in China. Concomitant inflammatory state further boosts the mortality due to cardiovascular events in patients with CKD undergoing dialysis. There is a general notion that Omega-3 fatty acids including docosahexaenoic acids (DHA) and eicosapentaenoic (EPA) have certain health benefits perhaps via the regulation of inflammation. However, the anti-inflammatory effect of omega-3 fatty acids in patients with CKD is controversial. We analyzed the data of oral supplementation of omega-3 fatty acids in CKD patients by searching literature on database from inception to August 2016. The analysis included randomized controlled trials (RCTs) derived from multiple databases, and the effect of omega-3 fatty acids supplementation versus the control cohorts were compared. All of the data analysis was calculated by RevMan 5.2. A total of 12 RCTs involving 487 patients were included in the meta-analysis. Among them 254 patients received omega-3 fatty acids and 233 patients served as controls who received placebo. The meta-analysis revealed no statistical significance in serum levels of C-reactive protein (CRP) (SMD, -0.20; 95% CI, -0.44 to 0.05; P = 0.11), IL-6 (SMD, 0.00; 95% CI, -0.33 to 0.33; P = 0.99) and TNF-α (SMD, 0.14; 95% CI, -0.17 to 0.44; P = 0.38) between the omega-3 fatty acids supplementation group and control. This suggested that there is insufficient evidence to conclude the benefit of omega-3 fatty acids oral supplementation in reducing serum levels of CRP, IL-6 and TNF-α in patients with CKD. © 2017 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.

  11. Chronic low grade inflammation measured by dietary inflammatory index and its association with obesity among school teachers in Yangon, Myanmar.

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    San, Khin Mittar Moe; Fahmida, Umi; Wijaksono, Fiastuti; Lin, Htin; Zaw, Ko Ko; Htet, Min Kyaw

    2018-01-01

    This study was aimed to investigate the association between obesity and chronic low grade inflammation (CLGI) measured by Dietary Inflammatory Index (DII) as a proxy indicator of CLGI among obese and non-obese teachers. We conducted a cross sectional study among 128 non-obese (BMI =25) female teachers aged 25-60 years from six urban schools in Yangon, Myanmar between January and March 2015. Usual dietary intake was collected by 3-day nonconsecutive estimated 24 hour's dietary records and semi-quantitative Food Frequency Questionnaires. Adapted DII was calculated by standardized methods using literature-derived population-based dietary inflammatory weights of 31 food parameters. C-reactive protein (CRP) was analysed by a sandwich Enzyme-Linked Immunosorbent Assay (ELISA) technique. Mean DII between obese and non-obese was compared by independent t test. The association between obesity indices and high DII (DII >=1.1) and high CRP (>3 mg/L) were investigated by logistic regression. Obese teachers had lower intakes of anti-inflammatory nutrients (vitamin B-6, vitamin A and zinc)/food (onion) compared with non-obese teachers (p<0.05) and obesity was significantly associated with CRP (Odd ratio (OR)=5.5, 95% Confidence interval (CI) 1.2-24.1, p=0.02). However, there was no significant association between obesity and DII (OR=1.4, 95% CI -0.8-2.3, p=0.23). Role of antiinflammatory foods should be promoted for prevention of obesity and related diseases. Further use of DII among Myanmar general population for prevention of obesity and its related diseases should be explored with longitudinal studies.

  12. Asthma-COPD overlap. Clinical relevance of genomic signatures of type 2 inflammation in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Christenson, Stephanie A; Steiling, Katrina; van den Berge, Maarten; Hijazi, Kahkeshan; Hiemstra, Pieter S; Postma, Dirkje S; Lenburg, Marc E; Spira, Avrum; Woodruff, Prescott G

    2015-04-01

    Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and likely includes a subgroup that is biologically comparable to asthma. Studying asthma-associated gene expression changes in COPD could add insight into COPD pathogenesis and reveal biomarkers that predict a favorable response to corticosteroids. To determine whether asthma-associated gene signatures are increased in COPD and associated with asthma-related features. We compared disease-associated airway epithelial gene expression alterations in an asthma cohort (n = 105) and two COPD cohorts (n = 237, 171). The T helper type 2 (Th2) signature (T2S) score, a gene expression metric induced in Th2-high asthma, was evaluated in these COPD cohorts. The T2S score was correlated with asthma-related features and response to corticosteroids in COPD in a randomized, placebo-controlled trial, the Groningen and Leiden Universities study of Corticosteroids in Obstructive Lung Disease (GLUCOLD; n = 89). The 200 genes most differentially expressed in asthma versus healthy control subjects were enriched among genes associated with more severe airflow obstruction in these COPD cohorts (P COPD cohorts. Higher T2S scores correlated with increased airway wall eosinophil counts (P = 0.003), blood eosinophil percentage (P = 0.03), bronchodilator reversibility (P = 0.01), and improvement in hyperinflation after corticosteroid treatment (P = 0.019) in GLUCOLD. These data identify airway gene expression alterations that can co-occur in asthma and COPD. The association of the T2S score with increased severity and "asthma-like" features (including a favorable corticosteroid response) in COPD suggests that Th2 inflammation is important in a COPD subset that cannot be identified by clinical history of asthma.

  13. Asthma–COPD Overlap. Clinical Relevance of Genomic Signatures of Type 2 Inflammation in Chronic Obstructive Pulmonary Disease

    Science.gov (United States)

    Steiling, Katrina; van den Berge, Maarten; Hijazi, Kahkeshan; Hiemstra, Pieter S.; Postma, Dirkje S.; Lenburg, Marc E.; Spira, Avrum; Woodruff, Prescott G.

    2015-01-01

    Rationale: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and likely includes a subgroup that is biologically comparable to asthma. Studying asthma-associated gene expression changes in COPD could add insight into COPD pathogenesis and reveal biomarkers that predict a favorable response to corticosteroids. Objectives: To determine whether asthma-associated gene signatures are increased in COPD and associated with asthma-related features. Methods: We compared disease-associated airway epithelial gene expression alterations in an asthma cohort (n = 105) and two COPD cohorts (n = 237, 171). The T helper type 2 (Th2) signature (T2S) score, a gene expression metric induced in Th2-high asthma, was evaluated in these COPD cohorts. The T2S score was correlated with asthma-related features and response to corticosteroids in COPD in a randomized, placebo-controlled trial, the Groningen and Leiden Universities study of Corticosteroids in Obstructive Lung Disease (GLUCOLD; n = 89). Measurements and Main Results: The 200 genes most differentially expressed in asthma versus healthy control subjects were enriched among genes associated with more severe airflow obstruction in these COPD cohorts (P COPD cohorts. Higher T2S scores correlated with increased airway wall eosinophil counts (P = 0.003), blood eosinophil percentage (P = 0.03), bronchodilator reversibility (P = 0.01), and improvement in hyperinflation after corticosteroid treatment (P = 0.019) in GLUCOLD. Conclusions: These data identify airway gene expression alterations that can co-occur in asthma and COPD. The association of the T2S score with increased severity and “asthma-like” features (including a favorable corticosteroid response) in COPD suggests that Th2 inflammation is important in a COPD subset that cannot be identified by clinical history of asthma. PMID:25611785

  14. Restoring Cystic Fibrosis Transmembrane Conductance Regulator Function Reduces Airway Bacteria and Inflammation in People with Cystic Fibrosis and Chronic Lung Infections.

    Science.gov (United States)

    Hisert, Katherine B; Heltshe, Sonya L; Pope, Christopher; Jorth, Peter; Wu, Xia; Edwards, Rachael M; Radey, Matthew; Accurso, Frank J; Wolter, Daniel J; Cooke, Gordon; Adam, Ryan J; Carter, Suzanne; Grogan, Brenda; Launspach, Janice L; Donnelly, Seamas C; Gallagher, Charles G; Bruce, James E; Stoltz, David A; Welsh, Michael J; Hoffman, Lucas R; McKone, Edward F; Singh, Pradeep K

    2017-06-15

    Previous work indicates that ivacaftor improves cystic fibrosis transmembrane conductance regulator (CFTR) activity and lung function in people with cystic fibrosis and G551D-CFTR mutations but does not reduce density of bacteria or markers of inflammation in the airway. These findings raise the possibility that infection and inflammation may progress independently of CFTR activity once cystic fibrosis lung disease is established. To better understand the relationship between CFTR activity, airway microbiology and inflammation, and lung function in subjects with cystic fibrosis and chronic airway infections. We studied 12 subjects with G551D-CFTR mutations and chronic airway infections before and after ivacaftor. We measured lung function, sputum bacterial content, and inflammation, and obtained chest computed tomography scans. Ivacaftor produced rapid decreases in sputum Pseudomonas aeruginosa density that began within 48 hours and continued in the first year of treatment. However, no subject eradicated their infecting P. aeruginosa strain, and after the first year P. aeruginosa densities rebounded. Sputum total bacterial concentrations also decreased, but less than P. aeruginosa. Sputum inflammatory measures decreased significantly in the first week of treatment and continued to decline over 2 years. Computed tomography scans obtained before and 1 year after ivacaftor treatment revealed that ivacaftor decreased airway mucous plugging. Ivacaftor caused marked reductions in sputum P. aeruginosa density and airway inflammation and produced modest improvements in radiographic lung disease in subjects with G551D-CFTR mutations. However, P. aeruginosa airway infection persisted. Thus, measures that control infection may be required to realize the full benefits of CFTR-targeting treatments.

  15. The effects of grounding (earthing on inflammation, the immune response, wound healing, and prevention and treatment of chronic inflammatory and autoimmune diseases

    Directory of Open Access Journals (Sweden)

    Oschman JL

    2015-03-01

    Full Text Available James L Oschman,1 Gaétan Chevalier,2 Richard Brown3 1Nature’s Own Research Association, Dover, NH, USA; 2Developmental and Cell Biology Department, University of California at Irvine, Irvine, CA, USA; 3Human Physiology Department, University of Oregon, Eugene, OR, USA Abstract: Multi-disciplinary research has revealed that electrically conductive contact of the human body with the surface of the Earth (grounding or earthing produces intriguing effects on physiology and health. Such effects relate to inflammation, immune responses, wound healing, and prevention and treatment of chronic inflammatory and autoimmune diseases. The purpose of this report is two-fold: to 1 inform researchers about what appears to be a new perspective to the study of inflammation, and 2 alert researchers that the length of time and degree (resistance to ground of grounding of experimental animals is an important but usually overlooked factor that can influence outcomes of studies of inflammation, wound healing, and tumorigenesis. Specifically, grounding an organism produces measurable differences in the concentrations of white blood cells, cytokines, and other molecules involved in the inflammatory response. We present several hypotheses to explain observed effects, based on current research results and our understanding of the electronic aspects of cell and tissue physiology, cell biology, biophysics, and biochemistry. An experimental injury to muscles, known as delayed onset muscle soreness, has been used to monitor the immune response under grounded versus ungrounded conditions. Grounding reduces pain and alters the numbers of circulating neutrophils and lymphocytes, and also affects various circulating chemical factors related to inflammation. Keywords: chronic inflammation, immune system, wound repair, white blood cells, macrophages, autoimmune disorders

  16. Signs of ongoing inflammation in female patients with chronic widespread pain: A multivariate, explorative, cross-sectional study of blood samples.

    Science.gov (United States)

    Gerdle, Björn; Ghafouri, Bijar; Ghafouri, Nazdar; Bäckryd, Emmanuel; Gordh, Torsten

    2017-03-01

    This cross-sectional study investigates the plasma inflammatory profile of chronic widespread pain (CWP) patients compared to healthy controls (CON). Rather than analyzing a relatively few substances at a time, we used a new multiplex proximity extension assay (PEA) panel that enabled the simultaneous analysis of 92 inflammation-related proteins, mainly cytokines and chemokines.Seventeen women with CWP and 21 female CON participated and a venous blood sample was drawn from all subjects. Pain intensity and pain thresholds for pressure, heat, and cold were registered. A PEA panel (92 proteins) was used to analyze the blood samples. Multivariate data analysis by projection was used in the statistical analyses.Eleven proteins significantly differentiated the CON and CWP subjects (R = 0.58, Q = 0.37, analysis of variance of cross-validated predictive residuals P = 0.006). It was not possible to significantly regress pain thresholds within each group (CON or CWP). Positive significant correlations existed between several proteins and pain intensities in CWP, but the model reliability of the regression was poor.CWP was associated with systemic low-grade inflammation. Larger studies are needed to confirm the results and to investigate which alterations are condition-specific and which are common across chronic pain conditions. The presence of inflammation could promote the spreading of pain, a hallmark sign of CWP. As it has been suggested that prevalent comorbidities to pain (e.g., depression and anxiety, poor sleep, and tiredness) also are associated with inflammation, it will be important to determine whether inflammation may be a common mediator.

  17. Rat strain differences in levels and effects of chronic inflammation due to intratracheal instillation of quartz on lung tumorigenesis induced by DHPN.

    Science.gov (United States)

    Nakano, Yuko; Yokohira, Masanao; Hashimoto, Nozomi; Yamakawa, Keiko; Kishi, Sosuke; Ninomiya, Fumiko; Kanie, Shohei; Saoo, Kousuke; Imaida, Katsumi

    2014-10-01

    Chronic inflammatory effects of single intratracheal instillation (i.t.) of quartz on rat lung tumorigenesis were examined using 4 different animal models. At first, in order to determine an appropriate dose of quartz i.t. to promote lung tumorigenesis, F344 male rats were administrated single 0, 0.5, 1, 2 or 4 mg quartz/rat after initiation by N-bis(2-hydroxypropyl) nitrosamine (DHPN). Further studies were performed to examine strain differences of the effects of chronic inflammation caused by quartz i.t. in 3 strains of rat, i.e. F344, Wistar-Hannover and SD. Each was instilled with 2mg quartz/rat after DHPN administration and sacrificed in week 24. In addition, strain differences in generation of inflammation were determined at days 1 and 28. Finally, for determination of long-term effects period, F344 and Wistar-Hannover rats were similarly treated, but the experiment was terminated at week 52. In F344 rats, the tumor areas in DHPN treated groups showed a tendency to increase along with the dose of quartz. F344 rats demonstrated the highest and Wistar-Hannover rats the lowest sensitivity to quartz in acute and chronic phases in the 3 strains. In 52 week, in F344 rats, the multiplicity of tumors and the serum concentration of IL-6 in the group treated with DHPN and quartz were significantly increased. The present experiments indicated that chronic inflammation due to quartz instillation exerted promoting effects on lung carcinogenesis in F344, SD and Wistar-Hannover rats. The strain differences in tumor promotion appeared to correlate with inflammatory reactions to quartz and increase of IL-6. Copyright © 2014 Elsevier GmbH. All rights reserved.

  18. Chronic inflammation and pain inside the mandibular jaw and a 10-year forgotten amalgam filling in an alveolar cavity of an extracted molar tooth.

    Science.gov (United States)

    Kaufmann, Thomas; Bloch, Catrin; Schmidt, Wolfgang; Jonas, Ludwig

    2005-01-01

    A 55-year-old woman, suffered from severe pain in her mandibular jaw for several years. A metallic artifact of about 2(3) mm was detected by a panorama radiography in an edentulous region with a surrounding inflammation in close contact to the canal of the mandibular nerve. Inflammated tissue with the central metallic inclusion was removed from the bone under local anesthesia and operation. Postoperatively, pain and missensitivity disappeared within 1 week. Although the patient had no macroscopically visible so-called amalgam tattoo, the metallic cube was identified as amalgam by the detection of mercury, silver, tin, copper, and zinc using energy dispersive X-ray analysis (EDX) in a scanning electron microscope (SEM). Nevertheless, brown to black pigments in the connective tissue matrix and inside histiocytes, fibroblasts, and multinucleated foreign giant cells of the surrounding inflammatory tissue were observed by light and electron microscopy. However, the elemental analysis by EDX in SEM or by electron energy loss spectroscopy in transmission electron microscope detected only silver, tin, and sulfur but no mercury in these precipitates and in the residual bodies of phagocytes. The presented case demonstrates a seldom complication of amalgam deposition in the tissue. The authors assume that the chronic pain results from a forgotten amalgam filling inside an alveole after extraction of a molar tooth, causing a chronic inflammation by resolving mercury and other toxic elements out of the metallic artifact.

  19. Q Fever: An Old but Still a Poorly Understood Disease

    Directory of Open Access Journals (Sweden)

    Hamidreza Honarmand

    2012-01-01

    Full Text Available Q fever is a bacterial infection affecting mainly the lungs, liver, and heart. It is found around the world and is caused by the bacteria Coxiella burnetii. The bacteria affects sheep, goats, cattle, dogs, cats, birds, rodents, and ticks. Infected animals shed this bacteria in birth products, feces, milk, and urine. Humans usually get Q fever by breathing in contaminated droplets released by infected animals and drinking raw milk. People at highest risk for this infection are farmers, laboratory workers, sheep and dairy workers, and veterinarians. Chronic Q fever develops in people who have been infected for more than 6 months. It usually takes about 20 days after exposure to the bacteria for symptoms to occur. Most cases are mild, yet some severe cases have been reported. Symptoms of acute Q fever may include: chest pain with breathing, cough, fever, headache, jaundice, muscle pains, and shortness of breath. Symptoms of chronic Q fever may include chills, fatigue, night sweats, prolonged fever, and shortness of breath. Q fever is diagnosed with a blood antibody test. The main treatment for the disease is with antibiotics. For acute Q fever, doxycycline is recommended. For chronic Q fever, a combination of doxycycline and hydroxychloroquine is often used long term. Complications are cirrhosis, hepatitis, encephalitis, endocarditis, pericarditis, myocarditis, interstitial pulmonary fibrosis, meningitis, and pneumonia. People at risk should always: carefully dispose of animal products that may be infected, disinfect any contaminated areas, and thoroughly wash their hands. Pasteurizing milk can also help prevent Q fever.

  20. The effects of grounding (earthing) on inflammation, the immune response, wound healing, and prevention and treatment of chronic inflammatory and autoimmune diseases.

    Science.gov (United States)

    Oschman, James L; Chevalier, Gaétan; Brown, Richard

    2015-01-01

    Multi-disciplinary research has revealed that electrically conductive contact of the human body with the surface of the Earth (grounding or earthing) produces intriguing effects on physiology and health. Such effects relate to inflammation, immune responses, wound healing, and prevention and treatment of chronic inflammatory and autoimmune diseases. The purpose of this report is two-fold: to 1) inform researchers about what appears to be a new perspective to the study of inflammation, and 2) alert researchers that the length of time and degree (resistance to ground) of grounding of experimental animals is an important but usually overlooked factor that can influence outcomes of studies of inflammation, wound healing, and tumorigenesis. Specifically, grounding an organism produces measurable differences in the concentrations of white blood cells, cytokines, and other molecules involved in the inflammatory response. We present several hypotheses to explain observed effects, based on current research results and our understanding of the electronic aspects of cell and tissue physiology, cell biology, biophysics, and biochemistry. An experimental injury to muscles, known as delayed onset muscle soreness, has been used to monitor the immune response under grounded versus ungrounded conditions. Grounding reduces pain and alters the numbers of circulating neutrophils and lymphocytes, and also affects various circulating chemical factors related to inflammation.

  1. Hydrogen-rich saline inhibits tobacco smoke-induced chronic obstructive pulmonary disease by alleviating airway inflammation and mucus hypersecretion in rats.

    Science.gov (United States)

    Liu, Zibing; Geng, Wenye; Jiang, Chuanwei; Zhao, Shujun; Liu, Yong; Zhang, Ying; Qin, Shucun; Li, Chenxu; Zhang, Xinfang; Si, Yanhong

    2017-09-01

    Chronic obstructive pulmonary disease induced by tobacco smoke has been regarded as a great health problem worldwide. The purpose of this study is to evaluate the protective effect of hydrogen-rich saline, a novel antioxidant, on chronic obstructive pulmonary disease and explore the underlying mechanism. Sprague-Dawley rats were made chronic obstructive pulmonary disease models via tobacco smoke exposure for 12 weeks and the rats were treated with 10 ml/kg hydrogen-rich saline intraperitoneally during the last 4 weeks. Lung function testing indicated hydrogen-rich saline decreased lung airway resistance and increased lung compliance and the ratio of forced expiratory volume in 0.1 s/forced vital capacity in chronic obstructive pulmonary disease rats. Histological analysis revealed that hydrogen-rich saline alleviated morphological impairments of lung in tobacco smoke-induced chronic obstructive pulmonary disease rats. ELISA assay showed hydrogen-rich saline lowered the levels of pro-inflammatory cytokines (IL-8 and IL-6) and anti-inflammatory cytokine IL-10 in bronchoalveolar lavage fluid and serum of chronic obstructive pulmonary disease rats. The content of malondialdehyde in lung tissue and serum was also determined and the data indicated hydrogen-rich saline suppressed oxidative stress reaction. The protein expressions of mucin MUC5C and aquaporin 5 involved in mucus hypersecretion were analyzed by Western blot and ELISA and the data revealed that hydrogen-rich saline down-regulated MUC5AC level in bronchoalveolar lavage fluid and lung tissue and up-regulated aquaporin 5 level in lung tissue of chronic obstructive pulmonary disease rats. In conclusion, these results suggest that administration of hydrogen-rich saline exhibits significant protective effect on chronic obstructive pulmonary disease through alleviating inflammation, reducing oxidative stress and lessening mucus hypersecretion in tobacco smoke-induced chronic obstructive pulmonary disease rats

  2. Intracellular heavy metal nanoparticle storage: progressive accumulation within lymph nodes with transformation from chronic inflammation to malignancy

    Directory of Open Access Journals (Sweden)

    Tommaso Iannitti

    2010-11-01

    Full Text Available Tommaso Iannitti1, Stefania Capone2, Antonietta Gatti3, Frederico Capitani4, Cetta Francesco5,6, Beniamino Palmieri21Department of Biological and Biomedical Sciences, Glasgow Caledonian University, Glasgow, UK; 2Department of General Surgery and Surgical Specialties, 3Laboratory of Biomaterials, Department of Specialistic Surgeries, Head and Neck Medical School and Surgical Clinic, University of Modena and Reggio Emilia, Italy; 4Laboratory of Nanodiagnostics, San Vito, Modena, Italy 5Department of Surgery, University of Siena, Siena; 6Institute of Geriatrics, Pio Albergo Trivulzio Hospital, Milan, ItalyAbstract: A 25-year-old man had complained of sudden fever spikes for two years and his blood tests were within the normal range. In 1993, a surgical biopsy of swollen left inguinal lymph nodes was negative for malignancy, but showed reactive lymphadenitis and widespread sinus histiocytosis. A concomitant needle biopsy of the periaortic lymph nodes and a bone marrow aspirate were also negative. In 1994, after an emergency hospital admission because of a sport-related thoracic trauma, a right inguinal lymph node biopsy demonstrated Hodgkin’s lymphoma Stage IVB (scleronodular mixed cell subtype. Although it was improved by chemotherapy, the disease suddenly relapsed, and a further lymph node biopsy was performed in 1998 confirming the same diagnosis. Despite further treatment, the patient died of septic shock in 2004, at the age of 38 years. Retrospective analysis of the various specimens showed intracellular heavy metal nanoparticles within lymph node, bone marrow, and liver samples by field emission gun environmental scanning electron microscopy and energy dispersive spectroscopy. Heavy metals from environmental pollution may accumulate in sites far from the entry route and, in genetically conditioned individuals with tissue specificity, may act as cofactors for chronic inflammation or even malignant transformation. The present anecdotal report

  3. Donors in Semiconductors - are they Understood in Electronic Era?

    International Nuclear Information System (INIS)

    Dmochowski, Janusz E

    2007-01-01

    The physics of semiconductors and contemporary electronics cannot be understood without impurities. The hydrogen-like shallow donor (and acceptor) state of electron (hole) bound by Coulomb electrostatic force of excess charge of impurity is used to control conductivity of semiconductors and construct semiconductor diodes, transistors and numerous types of semiconductor electronic and optoelectronic devices, including lasers. Recently, surprisingly, the physics of impurity donors appeared to be much reacher. Experimental evidence has been provided for universal existence of other types of electronic states of the same donor impurity: i) mysterious, deep, DX-type state resulting in metastability - slow hysteresis phenomena - understood as two-electron, acceptor-like state of donor impurity, formed upon large lattice distortion or rearrangement around impurity and accompanying capture of second electron, resulting in negative electron correlation energy U; ii) deep, localized, fully symmetric, A1, one-electron donor state of substitutional impurity. The latter state can be formed from the 'ordinary' shallow hydrogen-like state in the process of strong localization of electron by short range, local potential of impurity core, preserving full (A 1 ) symmetry of the substitutional impurity in the host lattice. The 'anticrossing' of the two A 1 (shallow hydrogenic and deep localized) energy levels upon transformation is observed. All types of electronic states of impurity can be universally observed for the same donor impurity and mutual transformation between different states occur upon changing experimental conditions. The knowledge about existence and properties of these n ew , molecular type, donor states in semiconductors seems still await general recognition and positive application in contemporary material and device science and engineering

  4. Differences in the association of inflammation and tryptophan with depressive symptoms between white and non-white chronic dialysis patients

    NARCIS (Netherlands)

    Haverkamp, Gertrud L; Loosman, Wim L; Schouten, Robbert W; Franssen, Casper F; Kema, Ido P; van Diepen, Merel; Dekker, Friedo W; Siegert, Carl E; Honig, Adriaan

    Objective: Possibly, different biochemical parameters are involved in the development of depressive symptoms in white and non-white dialysis patients. We examined whether the association between inflammation and depressive symptoms and between tryptophan and depressive symptoms differs between white

  5. Hypogonadism in patients with chronic obstructive pulmonary disease: relationship with airflow limitation, muscle weakness and systemic inflammation

    Directory of Open Access Journals (Sweden)

    Rasha Galal Daabis

    2016-03-01

    Conclusion: Hypogonadism is highly prevalent in clinically stable COPD patients and is particularly related to the severity of the airway obstruction. Systemic inflammation is present in stable COPD patients and its intensity is related to the severity of the underlying disease and it predisposes to skeletal muscle weakness and exercise intolerance. However, we failed to find a significant association between hypogonadism and muscle weakness or systemic inflammation.

  6. The effect of PPE-induced emphysema and chronic LPS-induced pulmonary inflammation on atherosclerosis development in APOE*3-LEIDEN mice.

    Directory of Open Access Journals (Sweden)

    P Padmini S J Khedoe

    Full Text Available BACKGROUND: Chronic obstructive pulmonary disease (COPD is characterized by pulmonary inflammation, airways obstruction and emphysema, and is a risk factor for cardiovascular disease (CVD. However, the contribution of these individual COPD components to this increased risk is unknown. Therefore, the aim of this study was to determine the contribution of emphysema in the presence or absence of pulmonary inflammation to the increased risk of CVD, using a mouse model for atherosclerosis. Because smoke is a known risk factor for both COPD and CVD, emphysema was induced by intratracheal instillation of porcine pancreatic elastase (PPE. METHODS: Hyperlipidemic APOE*3-Leiden mice were intratracheally instilled with vehicle, 15 or 30 µg PPE and after 4 weeks, mice received a Western-type diet (WTD. To study the effect of emphysema combined with pulmonary inflammation on atherosclerosis, mice received 30 µg PPE and during WTD feeding, mice were intranasally instilled with vehicle or low-dose lipopolysaccharide (LPS; 1 µg/mouse, twice weekly. After 20 weeks WTD, mice were sacrificed and emphysema, pulmonary inflammation and atherosclerosis were analysed. RESULTS: Intratracheal PPE administration resulted in a dose-dependent increase in emphysema, whereas atherosclerotic lesion area was not affected by PPE treatment. Additional low-dose intranasal LPS administration induced a low-grade systemic IL-6 response, as compared to vehicle. Combining intratracheal PPE with intranasal LPS instillation significantly increased the number of pulmonary macrophages and neutrophils. Plasma lipids during the study were not different. LPS instillation caused a limited, but significant increase in the atherosclerotic lesion area. This increase was not further enhanced by PPE. CONCLUSION: This study shows for the first time that PPE-induced emphysema both in the presence and absence of pulmonary inflammation does not affect atherosclerotic lesion development.

  7. The effect of PPE-induced emphysema and chronic LPS-induced pulmonary inflammation on atherosclerosis development in APOE*3-LEIDEN mice.

    Science.gov (United States)

    Khedoe, P Padmini S J; Wong, Man C; Wagenaar, Gerry T M; Plomp, Jaap J; van Eck, Miranda; Havekes, Louis M; Rensen, Patrick C N; Hiemstra, Pieter S; Berbée, Jimmy F P

    2013-01-01

    Chronic obstructive pulmonary disease (COPD) is characterized by pulmonary inflammation, airways obstruction and emphysema, and is a risk factor for cardiovascular disease (CVD). However, the contribution of these individual COPD components to this increased risk is unknown. Therefore, the aim of this study was to determine the contribution of emphysema in the presence or absence of pulmonary inflammation to the increased risk of CVD, using a mouse model for atherosclerosis. Because smoke is a known risk factor for both COPD and CVD, emphysema was induced by intratracheal instillation of porcine pancreatic elastase (PPE). Hyperlipidemic APOE*3-Leiden mice were intratracheally instilled with vehicle, 15 or 30 µg PPE and after 4 weeks, mice received a Western-type diet (WTD). To study the effect of emphysema combined with pulmonary inflammation on atherosclerosis, mice received 30 µg PPE and during WTD feeding, mice were intranasally instilled with vehicle or low-dose lipopolysaccharide (LPS; 1 µg/mouse, twice weekly). After 20 weeks WTD, mice were sacrificed and emphysema, pulmonary inflammation and atherosclerosis were analysed. Intratracheal PPE administration resulted in a dose-dependent increase in emphysema, whereas atherosclerotic lesion area was not affected by PPE treatment. Additional low-dose intranasal LPS administration induced a low-grade systemic IL-6 response, as compared to vehicle. Combining intratracheal PPE with intranasal LPS instillation significantly increased the number of pulmonary macrophages and neutrophils. Plasma lipids during the study were not different. LPS instillation caused a limited, but significant increase in the atherosclerotic lesion area. This increase was not further enhanced by PPE. This study shows for the first time that PPE-induced emphysema both in the presence and absence of pulmonary inflammation does not affect atherosclerotic lesion development.

  8. Increased IgA responses to the LPS of commensal bacteria is associated with inflammation and activation of cell-mediated immunity in chronic fatigue syndrome.

    Science.gov (United States)

    Maes, Michael; Twisk, Frank N M; Kubera, Marta; Ringel, Karl; Leunis, Jean-Claude; Geffard, Michel

    2012-02-01

    Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is accompanied by a) systemic IgA/IgM responses against the lipopolysaccharides (LPS) of commensal bacteria; b) inflammation, e.g. increased plasma interleukin-(IL)1 and tumor necrosis factor (TNF)α; and c) activation of cell-mediated immunity (CMI), as demonstrated by increased neopterin. To study the relationships between the IgA/IgM responses to the LPS of microbiota, inflammation, CMI and the symptoms of ME/CFS we measured the IgA/IgM responses to the LPS of 6 different enterobacteria, serum IL-1, TNFα, neopterin, and elastase in 128 patients with ME/CFS and chronic fatigue (CF). Severity of symptoms was assessed by the Fibromyalgia and Chronic Fatigue Syndrome (FF) Rating Scale. Serum IL-1, TNFα, neopterin and elastase are significantly higher in patients with ME/CFS than in CF patients. There are significant and positive associations between the IgA responses to LPS and serum IL-1, TNFα, neopterin and elastase. Patients with an abnormally high IgA response show increased serum IL-1, TNFα and neopterin levels, and higher ratings on irritable bowel syndrome (IBS) than subjects with a normal IgA response. Serum IL-1, TNFα and neopterin are significantly related to fatigue, a flu-like malaise, autonomic symptoms, neurocognitive disorders, sadness and irritability. The findings show that increased IgA responses to commensal bacteria in ME/CFS are associated with inflammation and CMI activation, which are associated with symptom severity. It is concluded that increased translocation of commensal bacteria may be responsible for the disease activity in some ME/CFS patients. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. Effects of a treatment with Se-rich rice flour high in resistant starch on enteric dysbiosis and chronic inflammation in diabetic ICR mice.

    Science.gov (United States)

    Yuan, Huaibo; Wang, Wenjuan; Chen, Deyi; Zhu, Xiping; Meng, Lina

    2017-05-01

    Enteric dysbiosis is associated with chronic inflammation and interacts with obesity and insulin resistance. Obesity and diabetes are induced in ICR (Institute of Cancer Research) mice fed a high-fat diet and administered a streptozocin injection. These mice were treated with normal rice (NR), normal rice with a high resistant starch content (NRRS) or Se-rich rice (selenium-enriched rice) with a high resistant starch content (SRRS). Faecal cell counts of Bifidobacterium, Lactobacillus and Enterococcus were significantly higher in SRRS-treated mice than in diabetic controls, while Enterobacter cloacae were lower. Similar results were also found in NRRS-treated mice. In contrast, no significant difference was found between NR-treated and diabetic control groups. The treatments with SRRS and NRRS reduced the faecal pH values of the diabetic mice. Regarding the inflammatory factor levels, lower levels of serum C-reactive protein (CRP), tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), nuclear factor-k-gene binding (NF-κB) and leptin (LEP) and higher adiponutrin (ADPN) levels were found in the SRRS and NRRS-treated mice compared with the diabetic and NR-treated mice. In addition, the CRP, IL-6 and NF-κB levels in the SRRS-treated mice were significantly reduced compared with those observed in the NRRS-treated mice. The reverse transcription-PCR (RT-PCR) results showed that the SRRS and NRRS-treated mice presented higher expression levels of orphan G protein-coupled receptor 41 (GPR41) and orphan G protein-coupled receptor 43 (GPR43) proteins compared with diabetic mice and NR-treated mice. These results indicate that treatments with rice high in RS exert beneficial effects by improving enteric dysbiosis and chronic inflammation. In addition, selenium and RS may exert synergistic effects on chronic inflammation. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  10. Patients with HBV-related acute-on-chronic liver failure have increased concentrations of extracellular histones aggravating cellular damage and systemic inflammation.

    Science.gov (United States)

    Li, X; Gou, C; Yao, L; Lei, Z; Gu, T; Ren, F; Wen, T

    2017-01-01

    Acute-on-chronic liver failure (ACLF) is the most common type of liver failure and associated with grave consequences. Systemic inflammation has been linked to its pathogenesis and outcome, but the identifiable triggers are absent. Recently, extracellular histones, especially H4, have been recognized as important mediators of cell damage in various inflammatory conditions. This study aimed to investigate whether extracellular histones have clinical implications in patients with hepatitis B virus (HBV)-related ACLF. One hundred and twelve patients with HBV-related ACLF, 90 patients with chronic hepatitis B, 88 patients with HBV-related liver cirrhosis and 40 healthy volunteers were entered into this study. Plasma histone H4 levels, cytokine profile and clinical data were obtained. Besides, patient's sera were incubated overnight with human L02 hepatocytes or monocytic U937 cells in the presence or absence of antihistone H4 antibody, and cellular damage and cytokine production were evaluated. We found that plasma histone H4 levels were greatly increased in patients with ACLF as compared with chronic hepatitis B, liver cirrhosis and healthy control subjects and were significantly associated with disease severity, systemic inflammation and outcome. Notably, ACLF patients' sera incubation decreased cultured L02 cell integrity and induced profound cytokine production in the supernatant of U937 cells. Antihistone H4 antibody treatment abrogated these adverse effects, thus confirming a cause-effect relationship between extracellular histones and organ injury/dysfunction. The data support the hypothesis that the increased extracellular histone levels in ACLF patients may aggravate disease severity by inducing cellular injury and systemic inflammation. Histone-targeted therapies may have potentially interventional value in clinical practice. © 2016 John Wiley & Sons Ltd.

  11. Human endotoxemia as a model of systemic inflammation

    DEFF Research Database (Denmark)

    Krabbe, K.S.; Krogh-Madsen, R.; Taudorf, S.

    2008-01-01

    Systemic inflammation is a pathogenetic component in a vast number of acute and chronic diseases such as sepsis, trauma, type 2 diabetes, atherosclerosis, and Alzheimer's disease, all of which are associated with a substantial morbidity and mortality. However, the molecular mechanisms...... and physiological significance of the systemic inflammatory response are still not fully understood. The human endotoxin model, an in vivo model of systemic inflammation in which lipopolysaccharide is injected or infused intravenously in healthy volunteers, may be helpful in unravelling these issues. The present...

  12. Chronic tooth pulp inflammation induces persistent expression of phosphorylated ERK (pERK) and phosphorylated p38 (pp38) in trigeminal subnucleus caudalis

    Science.gov (United States)

    Worsley, M.A.; Allen, C.E.; Billinton, A.; King, A.E.; Boissonade, F.M.

    2014-01-01

    Background Extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase are transiently phosphorylated (activated) in the spinal cord and trigeminal nucleus by acute noxious stimuli. Acute stimulation of dental pulp induces short-lived ERK activation in trigeminal subnucleus caudalis (Vc), and p38 inhibition attenuates short-term sensitization in Vc induced by acute pulpal stimulation. We have developed a model to study central changes following chronic inflammation of dental pulp that induces long-term sensitization. Here, we examine the effects of chronic inflammation and acute stimulation on the expression of phosphorylated ERK (pERK), phosphorylated p38 (pp38) and Fos in Vc. Results Chronic inflammation alone induced bilateral expression of pERK and pp38 in Vc, but did not induce Fos expression. Stimulation of both non-inflamed and inflamed pulps significantly increased pERK and pp38 bilaterally; expression was greatest in inflamed, stimulated animals, and was similar following 10-min and 60-min stimulation. Stimulation for 60 min, but not 10 min, induced Fos in ipsilateral Vc; Fos expression was significantly greater in inflamed, stimulated animals. pERK was present in both neurons and astrocytes; pp38 was present in neurons and other non-neuronal, non-astrocytic cell types. Conclusions This study provides the first demonstration that chronic inflammation of tooth pulp induces persistent bilateral activation of ERK and p38 within Vc, and that this activation is further increased by acute stimulation. This altered activity in intracellular signaling is likely to be linked to the sensitization that is seen in our animal model and in patients with pulpitis. Our data indicate that pERK and pp38 are more accurate markers of central change than Fos expression. In our model, localization of pERK and pp38 within specific cell types differs from that seen following acute stimulation. This may indicate specific roles for different cell types in

  13. Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS): A lymphocytic reactive response of the central nervous system? A case report.

    Science.gov (United States)

    Wang, Xiaolin; Huang, Dehui; Huang, Xusheng; Zhang, Jiatang; Ran, Ye; Lou, Xin; Gui, Qiuping; Yu, Shengyuan

    2017-04-15

    Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroid (CLIPPERS) was first described in 2010. The characteristic clinical picture, radiological distribution and steroid response have been well-described in previous reports. However, the underlying pathogenesis and nosological position of CLIPPERS in the CNS require further investigation for the primary CNS lymphoma have been identified by autopsy subsequently. Here, we report a 51-year-old woman who was diagnosed with CLIPPERS but progressed to primary CNS lymphomatoid granulomatosis, which supports that CLIPPERS is not just an inflammatory CNS disorder. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Prevalence of malnutrition-inflammation complex syndrome and its correlation with thyroid hormones in chronic haemodialysis patients.

    Science.gov (United States)

    Chávez Valencia, Venice; Mejía Rodríguez, Oliva; Viveros Sandoval, Martha Eva; Abraham Bermúdez, Juan; Gutiérrez Castellanos, Sergio; Orizaga de la Cruz, Citlalli; Roa Córdova, Martha Alicia

    Low levels of thyroid hormones, total triiodothyronine (T3) and free triiodothyronine (FT3) in haemodialysis patients is a marker of malnutrition and inflammation and are predictors of mortality. The aim of this study was to determine the prevalence of malnutrition-inflammation complex syndrome in haemodialysis and its relationship with the thyroid hormones thyrotropin, T3, FT3 and free thyroxine (FT4), as well as to evaluate the prevalence of low FT3 syndrome and its correlation with nutritional and inflammatory markers. Cross-sectional, analytical and comparative study that enrolled 128 haemodialysis patients: 50.8% females; mean age 45.05±17.01 years; mean time on haemodialysis 45.4±38.8 months; 29.7% diabetics; 79.7% with hypertension. Serum thyroid hormones thyrotropin, T3, FT3 and FT4 concentrations were measured and Malnutritition-Inflammation Score (MIS) was applie to diagnostic. Mean thyroid hormone values were: thyroid hormones thyrotropin 2.48±1.8 mIU/ml (range: 0.015-9.5), T3 1.18±0.39 ng/ml (range 0.67-2.64), FT3 5.21±0.96pmol/l (range: 3.47-9.75); FT4 1.35±0.4 ng/ml (range: 0.52-2.57). Malnutrition-inflammation complex syndrome prevalence was 53.9%; 11.7% presented low FT3 levels. Serum T3 and FT3 concentrations inversely correlated with Malnutritition-Inflammation Score (MIS), while FT4 correlated positively with Malnutrition-Inflammation Score. In the linear regression analysis, low FT3 was associated with IL-6 (β= 0.265, p=.031), C-reactive protein (CRP) (β= -0.313, p=.018) and albumin (β= 0.276, p=.002). Low T3 and FT3 levels are correlated with malnutrition and inflammation parameters. Malnutrition-inflammation complex syndrome can affect serum concentrations of thyroid hormones. Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  15. Molecular Analysis of a Multistep Lung Cancer Model Induced by Chronic Inflammation Reveals Epigenetic Regulation of p16, Activation of the DNA Damage Response Pathway

    Directory of Open Access Journals (Sweden)

    David Blanco

    2007-10-01

    Full Text Available The molecular hallmarks of inflammation-mediated lung carcinogenesis have not been fully clarified, mainly due to the scarcity of appropriate animal models. We have used a silica-induced multistep lung carcinogenesis model driven by chronic inflammation to study the evolution of molecular markers, genetic alterations. We analyzed markers of DNA damage response (DDR, proliferative stress, telomeric stress: δ-H2AX, p16, p53, TERT. Lung cancer-related epigenetic, genetic alterations, including promoter hypermethylation status of p16(CDKN2A, APC, CDH13, Rassf1, Nore1A, as well as mutations of Tp53, epidermal growth factor receptor, K-ras, N-ras, c-H-ras, have been also studied. Our results showed DDR pathway activation in preneoplastic lesions, in association with inducible nitric oxide synthase, p53 induction. p16 was also induced in early tumorigenic progression, was inactivated in bronchiolar dysplasias, tumors. Remarkably, lack of mutations of Ras, epidermal growth factor receptor, a very low frequency of Tp53 mutations suggest that they are not required for tumorigenesis in this model. In contrast, epigenetic alterations in p16(CDKN2A, CDH13, APC, but not in Rassf1, Nore1A, were clearly observed. These data suggest the existence of a specific molecular signature of inflammation-driven lung carcinogenesis that shares some, but not all, of the molecular landmarks of chemically induced lung cancer.

  16. Expression of Fos protein in the rat central nervous system in response to noxious stimulation: effects of chronic inflammation of the superior cervical ganglion

    Directory of Open Access Journals (Sweden)

    Laudanna A.

    1998-01-01

    Full Text Available The aim of this study was to investigate the possible interactions between the nociceptive system, the sympathetic system and the inflammatory process. Thus, the superior cervical ganglion of rats was submitted to chronic inflammation and Fos expression was used as a marker for neuronal activity throughout central neurons following painful peripheral stimulation. The painful stimulus consisted of subcutaneously injected formalin applied to the supra-ocular region. Fos-positive neurons were identified by conventional immunohistochemical techniques, and analyzed from the obex through the cervical levels of the spinal cord. In the caudal sub-nucleus of the spinal trigeminal nuclear complex, the number of Fos-positive neurons was much higher in rats with inflammation of the superior cervical ganglion than in control rats, either sham-operated or with saline applied to the ganglion. There was a highly significant difference in the density of Fos-positive neurons between the inflamed and control groups. No significant difference was found between control groups. These results suggest that the inflammation of the superior cervical ganglion generated an increased responsiveness to painful stimuli, which may have been due to a diminished sympathetic influence upon the sensory peripheral innervation.

  17. Inflammation and elevated levels of fibroblast growth factor 23 are independent risk factors for death in chronic kidney disease.

    Science.gov (United States)

    Munoz Mendoza, Jair; Isakova, Tamara; Cai, Xuan; Bayes, Liz Y; Faul, Christian; Scialla, Julia J; Lash, James P; Chen, Jing; He, Jiang; Navaneethan, Sankar; Negrea, Lavinia; Rosas, Sylvia E; Kretzler, Matthias; Nessel, Lisa; Xie, Dawei; Anderson, Amanda Hyre; Raj, Dominic S; Wolf, Myles

    2017-03-01

    Inflammation is a consequence of chronic kidney disease (CKD) and is associated with adverse outcomes in many clinical settings. Inflammation stimulates production of fibroblast growth factor 23 (FGF23), high levels of which are independently associated with mortality in CKD. Few large-scale prospective studies have examined inflammation and mortality in patients with CKD, and none tested the interrelationships among inflammation, FGF23, and risk of death. Therefore, we conducted a prospective investigation of 3875 participants in the Chronic Renal Insufficiency Cohort (CRIC) study with CKD stages 2 to 4 to test the associations of baseline plasma interleukin-6, high-sensitivity C-reactive protein, and FGF23 levels with all-cause mortality, censoring at the onset of end-stage renal disease. During a median follow-up of 6.9 years, 550 participants died (20.5/1000 person-years) prior to end-stage renal disease. In separate multivariable-adjusted analyses, higher levels of interleukin-6 (hazard ratio per one standard deviation increase of natural log-transformed levels) 1.35 (95% confidence interval, 1.25-1.46), C-reactive protein 1.28 (1.16-1.40), and FGF23 1.45 (1.32-1.60) were each independently associated with increased risk of death. With further adjustment for FGF23, the risks of death associated with interleukin-6 and C-reactive protein were minimally attenuated. Compared to participants in the lowest quartiles of inflammation and FGF23, the multivariable-adjusted hazard ratio of death among those in the highest quartiles of both biomarkers was 4.38 (2.65-7.23) for interleukin-6 and FGF23, and 5.54 (3.04-10.09) for C-reactive protein and FGF23. Thus, elevated levels of interleukin-6, C-reactive protein, and FGF23 are independent risk factors for mortality in CKD. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  18. Elevated levels of serum sialic acid and high-sensitivity C-reactive protein: markers of systemic inflammation in patients with chronic heart failure.

    Science.gov (United States)

    Rajendiran, K S; Ananthanarayanan, R H; Satheesh, S; Rajappa, M

    2014-01-01

    Heart failure (HF) is a common, debilitating disorder in which the heart is unable to pump an adequate blood supply to the tissues. Although it has been shown that inflammation occurs in HF, inflammatory markers have yet to be defined. Inflammatory markers such as high-sensitivity C-reactive protein (hs-CRP), cytokines and serum sialic acid (SA) have been suggested as cardiovascular risk biomarkers. This study aims to assess the serum levels of inflammatory markers such as sialic acid and hs-CRP in chronic heart failure (CHF). Forty-eight patients with CHF and 30 healthy controls were recruited. Total sialic acid (TSA) and lipid-associated sialic acid (LASA), and the inflammatory marker hs-CRP, were assayed in all study subjects. N-terminal pro-brain natriuretic peptide (NT-proBNP) was assayed in the patient group only. Serum mean TSA and LASA were significantly higher in CHF patients when compared to healthy controls (P markers of systemic inflammation in chronic heart failure.

  19. Serum Immunoglobulin M Concentration Varies with Triglyceride Levels in an Adult Population: Tianjin Chronic Low-Grade Systemic Inflammation and Health (TCLSIHealth) Cohort Study.

    Science.gov (United States)

    Shi, Hongbin; Guo, Xiaoyan; Zhang, Qing; Wu, Hongmei; Du, Huanmin; Liu, Li; Wang, Chongjin; Xia, Yang; Liu, Xing; Li, Chunlei; Sun, Shaomei; Wang, Xing; Zhou, Ming; Jia, Qiyu; Zhao, Honglin; Song, Kun; Wei, Dianjun; Niu, Kaijun

    2015-01-01

    Persistent low-grade inflammation is thought to underlie the pathogenesis of many chronic diseases, such as cardiovascular diseases and metabolic syndrome. Autoimmunity is correlated with increased levels of chronic low-grade inflammation, and immunoglobulin M (IgM) is reactive to autoantigens and believed to be important for autoimmunity. Triglyceride (TG) is fatty acid carrier and initiator of oxidative stress, and it has been hypothesized that TG stimulates B cells to secrete IgM. However, few studies have investigated the relationship between TG and IgM in human populations. We designed a cross-sectional and prospective cohort study to evaluate how serum TG levels are related to IgM concentration. Participants were recruited from Tianjin Medical University General Hospital-Health Management Centre. Both a baseline cross-sectional (n = 10,808) and a prospective assessment (n = 2,615) were performed. Analysis of covariance was used in the cross-sectional analysis. After multiple adjustments for confounding factors, serum IgM level in the highest quartile of TG in males was significantly higher than levels in lower quartiles (P levels and changes of TG concentration in males (P = 0.04, standard β coefficient = 0.882). This cross-sectional and cohort study is the first to show that serum concentration of IgM varies with TG levels in adult male populations. Further research is needed to explore the mechanism by which TG leads to increased IgM concentration.

  20. Assessment of the reliability and consistency of the "malnutrition inflammation score" (MIS) in Mexican adults with chronic kidney disease for diagnosis of protein-energy wasting syndrome (PEW).

    Science.gov (United States)

    González-Ortiz, Ailema Janeth; Arce-Santander, Celene Viridiana; Vega-Vega, Olynka; Correa-Rotter, Ricardo; Espinosa-Cuevas, María de Los Angeles

    2014-10-04

    The protein-energy wasting syndrome (PEW) is a condition of malnutrition, inflammation, anorexia and wasting of body reserves resulting from inflammatory and non-inflammatory conditions in patients with chronic kidney disease (CKD).One way of assessing PEW, extensively described in the literature, is using the Malnutrition Inflammation Score (MIS). To assess the reliability and consistency of MIS for diagnosis of PEW in Mexican adults with CKD on hemodialysis (HD). Study of diagnostic tests. A sample of 45 adults with CKD on HD were analyzed during the period June-July 2014.The instrument was applied on 2 occasions; the test-retest reliability was calculated using the Intraclass Correlation Coefficient (ICC); the internal consistency of the questionnaire was analyzed using Cronbach's αcoefficient. A weighted Kappa test was used to estimate the validity of the instrument; the result was subsequently compared with the Bilbrey nutritional index (BNI). The reliability of the questionnaires, evaluated in the patient sample, was ICC=0.829.The agreement between MIS observations was considered adequate, k= 0.585 (p <0.001); when comparing it with BNI, a value of k = 0.114 was obtained (p <0.001).In order to estimate the tendency, a correlation test was performed. The r² correlation coefficient was 0.488 (P <0.001). MIS has adequate reliability and validity for diagnosing PEW in the population with chronic kidney disease on HD. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  1. Synergistic effects of green tea polyphenols and alphacalcidol on chronic inflammation-induced bone loss in female rats

    Science.gov (United States)

    Summary: Studies suggest that green tea polyphenols (GTP) or alphacalcidol is promising agent for preventing bone loss. Findings that GTP supplementation in the drinking water plus alphacalcidol administration resulted in increased bone mass via a decrease of oxidative stress and inflammation sugges...

  2. The difference in correlation between insulin resistance index and chronic inflammation in type 2 diabetes with and without metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Morteza Pourfarzam

    2016-01-01

    Conclusions: In T2DM with MetS, coexistence of elevated atherogenic indices, systemic inflammation, and association between HOMA-IR and TG/HDL-C ratio were seen. These factors are considered having important role in elevated CVD risk beyond MetS components in these patients.

  3. Pilot validation of objective malnutrition—inflammation scores in pediatric and adolescent cohort on chronic maintenance dialysis

    Directory of Open Access Journals (Sweden)

    Franca M Iorember

    2014-10-01

    Full Text Available Background: In recognition of the challenges inherent with the use of single-item indices for the diagnosis of malnutrition–inflammation morbidity in pediatric dialysis patients, to enhance accuracy, we validated a composite scoring system in a pilot study. The objective malnutrition—inflammation score seeks to validate the use of a composite scoring system as a tool for assessing malnutrition—inflammation burden in a pediatric dialysis population. Methods: We enrolled 20 patients on hemodialysis (n = 14 and peritoneal dialysis (n = 6 over a period of 12 months. We derived composite scores from selected indices of renal pathology, nutrition, dialysis adequacy, protein catabolism, and dialysis modality. We assessed reliability by a test–retest method and measured validity by defining the relationship of the indices with serum C-reactive protein in a multiple regression analysis. We calculated sensitivity, specificity, accuracy, and precision for the malnutrition—inflammation score. Results: The mean age was 12.8 years (standard deviation = 6.1, and male–female ratio was 12:8. Patients (n = 8 with elevated serum C-reactive protein (>0.3 mg/dL had higher composite score for malnutrition—inflammation morbidity. Similarly, the pediatric cohort on hemodialysis had higher score than those on peritoneal dialysis. Upon reliability testing, a low value of typical error (0.07 and high correlation coefficient (r = 0.95 supported validity of the instrument. Moreover, multiple regression analysis showed a strong predictive relationship (R2 = 0.9, p = 0.03 between the indices and serum C-reactive protein. Sensitivity of malnutrition—inflammation score was 62.5%, specificity was 83%, accuracy was 75%, and precision was 71%. Conclusion: Using criterion-validation method, we established the potential use of multi-diagnostic approach to quantify malnutrition—inflammation morbidity in a pediatric dialysis cohort

  4. Protective effect of bioactivity guided fractions of Ziziphus jujuba Mill. root bark against hepatic injury and chronic inflammation via inhibiting inflammatory markers and oxidative stress

    Directory of Open Access Journals (Sweden)

    Raghuram Kandimalla

    2016-09-01

    Full Text Available The tribal communities of North Eastern India rely on herbal medicine to cure various disease conditions. Ziziphus jujuba Mill. (Rhamnaceae is one of such medicinal plants used for curing liver ailments, insomnia, anemia, diarrhea, diabetic complications, cancer and loss of appetite. The present study was aimed to describe the protective ability of Z. jujuba root bark against hepatic injury and chronic inflammation. Bioactivity guided fractionation of Z. jujuba methanol extract (ZJME was performed using different solvents of increasing polarity viz. hexane (ZJHF, chloroform (ZJCF, ethyl acetate (ZJEAF, water (ZJWF and residue (ZJMR. In vitro antioxidant results revealed that both ZJME and ZJWF possess strong antioxidant activity among all the fractions and mother extract tested. Further, ZJME and ZJWF showed significant protection against CCl4 intoxicated HepG2 cell lines by means of increased cell viability and decreased LDH levels compared to control group. ZJME at 200, 400 mg/kg and ZJWF at 50, 100 mg/kg inhibited the lipid peroxidation and significantly restored the liver function markers (AST, ALT, ALP, LDH, SOD and CAT and cytokine levels (TNF-α, Il-1β and Il-10 in CCl4 induced acute liver damage in rats. All the results were comparable with standard drug silymarin which was further confirmed by histopathology analysis of liver. Similarly, inflammation and increase inflammatory cytokines levels of carrageenan induced paw edema in rats have been refurbished to normal levels on par with the standard drug indomethacin. ZJWF demonstrated potent response than ZJME in all the biological tests conducted. The results of the study signify the ability of Z. jujuba root bark as good therapeutic agent for liver toxicity and chronic inflammation.

  5. Sedentary Lifestyle and High-Carbohydrate Intake are Associated with Low-Grade Chronic Inflammation in Post-Menopause: A Cross-sectional Study.

    Science.gov (United States)

    Alves, Bruna Cherubini; Silva, Thaís Rasia da; Spritzer, Poli Mara

    2016-07-01

    Introduction Cardiovascular disease (CVD) is the leading cause of death in post menopausal women, and inflammation is involved in the atherosclerosis process. Purpose to assess whether dietary pattern, metabolic profile, body composition and physical activity are associated with low-grade chronic inflammation according to high-sensitivity C-reactive protein (hs-CRP) levels in postmenopausal women. Methods ninety-five postmenopausal participants, with no evidence of clinical disease, underwent anthropometric, metabolic and hormonal assessments. Usual dietary intake was assessed with a validated food frequency questionnaire, habitual physical activity was measured with a digital pedometer, and body composition was estimated by bioelectrical impedance analysis. Patients with hs-CRP ≥10 mg/L or using hormone therapy in the last three months before the study were excluded from the analysis. Participants were stratified according to hs-CRP lower or ≥3 mg/L. Sedentary lifestyle was defined as walking fewer than 6 thousand steps a day. Two-tailed Student's t-test, Wilcoxon-Mann-Whitney U or Chi-square (χ(2)) test were used to compare differences between groups. A logistic regression model was used to estimate the odds ratio of variables for high hs-CRP. Results participants with hs-CRP ≥3 mg/L had higher body mass index (BMI), body fat percentage, waist circumference (WC), triglycerides, glucose, and homeostasis model assessment of insulin resistance (HOMA-IR) (p = 0.01 for all variables) than women with hs-CRP sedentary lifestyle (p sedentary lifestyle (4.7, 95% confidence interval [95%CI] 1.4-15.5) and carbohydrate intake (2.9, 95%CI 1.1-7.7). Conclusions sedentary lifestyle and high-carbohydrate intake were associated with low-grade chronic inflammation and cardiovascular risk in postmenopause. Thieme Publicações Ltda Rio de Janeiro, Brazil.

  6. Association between serum levels of high sensitive C-reactive protein and inflammation activity in chronic gastritis patients.

    Science.gov (United States)

    Rahmani, Asghar; Moradkhani, Atefeh; Hafezi Ahmadi, Mohammad Reza; Jafari Heirdarlo, Ali; Abangah, Ghobad; Asadollahi, Khairollah; Sayehmiri, Kourosh

    2016-01-01

    Gastritis is an important premalignant lesion and recent studies suggested a production of inflammatory cytokine-like C-reactive protein during gastritis. This study aimed to determine any relationship between high sensitive C-reactive protein (hs-CRP) and inflammation activity among patients with gastritis. Demographic and clinical variables of participants were collected by a validated questionnaire. Using histology of the gastric mucosa, Helicobacter pylori status was investigated and serum concentrations of hs-CRP were measured among dyspeptic patients. Correlation between hs-CRP serum levels and inflammation activities was evaluated by logistic regression analysis. The relation between active inflammation and other variables was evaluated by logic link function model. Totally 239 patients (56.6% female) were analysed. The prevalence of mild, moderate and severe inflammation activities was 66.5%, 23.8% and 9.6% respectively. Mean ± SD of hs-CRP among men and women were 2.85 ± 2.84 mg/dl and 2.80 ± 4.80 mg/dl (p = 0.047) respectively. Mean ± SD of hs-CRP among patients with H. pylori infection, gland atrophy, metaplasia and dysplasia were 2.83 ± 3.80 mg/dl, 3.52 ± 5.1 mg/dl, 2.22 ± 2.3 mg/dl and 5.3 ± 5.04 mg/dl respectively. Relationship between hs-CRP and inflammation activities (p gastritis, elevated hs-CRP levels may be considered as a predictive marker of changes in gastric mucosa and a promising therapeutic target for patients with gastritis.

  7. Intima-media thickness is associated with inflammation and traditional cardiovascular risk factors in non-dialysis-dependent patients with chronic kidney disease.

    Science.gov (United States)

    Lemos, Marcelo M; Jancikic, Alessandra D B; Sanches, Fabiana M R; Christofalo, Dejaldo M; Ajzen, Sérgio A; Carvalho, Aluízio B; Draibe, Sérgio A; Canziani, Maria Eugênia F

    2010-01-01

    Mortality due to cardiovascular causes is high in chronic kidney disease (CKD). Intima-media thickness (IMT) and inflammation are early atherosclerosis markers, although data are lacking about their association in the CKD non-dialysis-dependent (CKD-NDD) population. The aim of the present study was to evaluate the association between IMT, inflammation and other cardiovascular risk factors in such patients. CKD-NDD patients (n = 122) were subjected to measurements of carotid IMT and inflammatory marker levels in a cross-sectional study. Mean patient age was 55.2 +/- 11.3 years (61.5% males). Median C-reactive protein (CRP) was 0.28 mg/dl (0.03-14.2). The median interleukin (IL)-6 count was 4.75 pg/ml (0.7-243), the mean adiponectin was 27.8 +/- 7.3 ng/ml and the mean IMT was 0.61 +/- 0.19 mm. Four (3.3%) patients had IMT above the normal range. IMT was higher in males (p < 0.001), patients with estimated glomerular filtration rate <60 ml/min (p = 0.030), inflammation (p = 0.005) and higher IL-6 levels (p = 0.023). IMT was correlated with age (R = 0.538; p < 0.001), waist circumference (R = 0.235; p = 0.016), CRP (R = 0.191; p = 0.035) and systolic blood pressure (R = 0.181; p = 0.048). In a multiple regression analysis, the independent determinants of IMT were age (beta = 0.512; p < 0.001) and CRP levels (beta = 0.159; p = 0.041). The present study demonstrated that although the IMT values were within the normal range, there was a clear association of IMT with age, as well as with inflammation in an asymptomatic CKD-NDD population. Copyright 2010 S. Karger AG, Basel.

  8. Chronic Inflammation: Synergistic Interactions of Recruiting Macrophages (TAMs) and Eosinophils (Eos) with Host Mast Cells (MCs) and Tumorigenesis in CALTs. M-CSF, Suitable Biomarker for Cancer Diagnosis!

    Energy Technology Data Exchange (ETDEWEB)

    Khatami, Mahin [Inflammation and Cancer Biology, National Cancer Institute (Ret), the National Institutes of Health, Bethesda, MD 20817 (United States)

    2014-01-27

    Ongoing debates, misunderstandings and controversies on the role of inflammation in cancer have been extremely costly for taxpayers and cancer patients for over four decades. A reason for repeated failed clinical trials (90% ± 5 failure rates) is heavy investment on numerous genetic mutations (molecular false-flags) in the chaotic molecular landscape of site-specific cancers which are used for “targeted” therapies or “personalized” medicine. Recently, unresolved/chronic inflammation was defined as loss of balance between two tightly regulated and biologically opposing arms of acute inflammation (“Yin”–“Yang” or immune surveillance). Chronic inflammation could differentially erode architectural integrities in host immune-privileged or immune-responsive tissues as a common denominator in initiation and progression of nearly all age-associated neurodegenerative and autoimmune diseases and/or cancer. Analyses of data on our “accidental” discoveries in 1980s on models of acute and chronic inflammatory diseases in conjunctival-associated lymphoid tissues (CALTs) demonstrated at least three stages of interactions between resident (host) and recruited immune cells: (a), acute phase; activation of mast cells (MCs), IgE Abs, histamine and prostaglandin synthesis; (b), intermediate phase; down-regulation phenomenon, exhausted/degranulated MCs, heavy eosinophils (Eos) infiltrations into epithelia and goblet cells (GCs), tissue hypertrophy and neovascularization; and (c), chronic phase; induction of lymphoid hyperplasia, activated macrophages (Mϕs), increased (irregular size) B and plasma cells, loss of integrity of lymphoid tissue capsular membrane, presence of histiocytes, follicular and germinal center formation, increased ratios of local IgG1/IgG2, epithelial thickening (growth) and/or thinning (necrosis) and angiogenesis. Results are suggestive of first evidence for direct association between inflammation and identifiable phases of immune

  9. Chronic Inflammation: Synergistic Interactions of Recruiting Macrophages (TAMs) and Eosinophils (Eos) with Host Mast Cells (MCs) and Tumorigenesis in CALTs. M-CSF, Suitable Biomarker for Cancer Diagnosis!

    International Nuclear Information System (INIS)

    Khatami, Mahin

    2014-01-01

    Ongoing debates, misunderstandings and controversies on the role of inflammation in cancer have been extremely costly for taxpayers and cancer patients for over four decades. A reason for repeated failed clinical trials (90% ± 5 failure rates) is heavy investment on numerous genetic mutations (molecular false-flags) in the chaotic molecular landscape of site-specific cancers which are used for “targeted” therapies or “personalized” medicine. Recently, unresolved/chronic inflammation was defined as loss of balance between two tightly regulated and biologically opposing arms of acute inflammation (“Yin”–“Yang” or immune surveillance). Chronic inflammation could differentially erode architectural integrities in host immune-privileged or immune-responsive tissues as a common denominator in initiation and progression of nearly all age-associated neurodegenerative and autoimmune diseases and/or cancer. Analyses of data on our “accidental” discoveries in 1980s on models of acute and chronic inflammatory diseases in conjunctival-associated lymphoid tissues (CALTs) demonstrated at least three stages of interactions between resident (host) and recruited immune cells: (a), acute phase; activation of mast cells (MCs), IgE Abs, histamine and prostaglandin synthesis; (b), intermediate phase; down-regulation phenomenon, exhausted/degranulated MCs, heavy eosinophils (Eos) infiltrations into epithelia and goblet cells (GCs), tissue hypertrophy and neovascularization; and (c), chronic phase; induction of lymphoid hyperplasia, activated macrophages (Mϕs), increased (irregular size) B and plasma cells, loss of integrity of lymphoid tissue capsular membrane, presence of histiocytes, follicular and germinal center formation, increased ratios of local IgG1/IgG2, epithelial thickening (growth) and/or thinning (necrosis) and angiogenesis. Results are suggestive of first evidence for direct association between inflammation and identifiable phases of immune

  10. Chronic Inflammation: Synergistic Interactions of Recruiting Macrophages (TAMs and Eosinophils (Eos with Host Mast Cells (MCs and Tumorigenesis in CALTs. M-CSF, Suitable Biomarker for Cancer Diagnosis!

    Directory of Open Access Journals (Sweden)

    Mahin Khatami

    2014-01-01

    Full Text Available Ongoing debates, misunderstandings and controversies on the role of inflammation in cancer have been extremely costly for taxpayers and cancer patients for over four decades. A reason for repeated failed clinical trials (90% ± 5 failure rates is heavy investment on numerous genetic mutations (molecular false-flags in the chaotic molecular landscape of site-specific cancers which are used for “targeted” therapies or “personalized” medicine. Recently, unresolved/chronic inflammation was defined as loss of balance between two tightly regulated and biologically opposing arms of acute inflammation (“Yin”–“Yang” or immune surveillance. Chronic inflammation could differentially erode architectural integrities in host immune-privileged or immune-responsive tissues as a common denominator in initiation and progression of nearly all age-associated neurodegenerative and autoimmune diseases and/or cancer. Analyses of data on our “accidental” discoveries in 1980s on models of acute and chronic inflammatory diseases in conjunctival-associated lymphoid tissues (CALTs demonstrated at least three stages of interactions between resident (host and recruited immune cells: (a, acute phase; activation of mast cells (MCs, IgE Abs, histamine and prostaglandin synthesis; (b, intermediate phase; down-regulation phenomenon, exhausted/degranulated MCs, heavy eosinophils (Eos infiltrations into epithelia and goblet cells (GCs, tissue hypertrophy and neovascularization; and (c, chronic phase; induction of lymphoid hyperplasia, activated macrophages (Mfs, increased (irregular size B and plasma cells, loss of integrity of lymphoid tissue capsular membrane, presence of histiocytes, follicular and germinal center formation, increased ratios of local IgG1/IgG2, epithelial thickening (growth and/or thinning (necrosis and angiogenesis. Results are suggestive of first evidence for direct association between inflammation and identifiable phases of immune

  11. Chronic maternal inflammation or high-fat-feeding programs offspring obesity in a sex-dependent manner

    DEFF Research Database (Denmark)

    Dudele, A; Hougaard, K S; Kjølby, M

    2017-01-01

    , characteristic of the obese state, provides a causal role for this disastrous fetal programming in mice. Methods: We exposed pregnant and lactating C57BL/6JBom female mice to either high-fat diet (HFD), or continuous infusion of lipopolysaccharide (LPS), a potent trigger of innate immunity, and studied offspring...... inflammatory response to HFD at adulthood. Conclusions: This supports our hypothesis and highlights the programming potential of inflammation in obese pregnancies....

  12. Chitotriosidase enzyme activity: is this a possible chronic inflammation marker in children with common variable immunodeficiency and early atherosclerosis?

    Science.gov (United States)

    Azarsız, Elif; Karaca, Neslihan; Levent, Erturk; Kutukculer, Necil; Sozmen, Eser

    2017-11-01

    Background Common variable immunodeficiency is a rare clinically symptomatic primary immunodeficiency disorder which manifests a wide variability of symptoms, complications. Atherosclerosis in common variable immunodeficiency patients has not been investigated yet contrary to other severe clinical complications. We aimed to investigate the chitotriosidase enzyme's role as an inflammation and atherosclerosis marker in paediatric common variable immunodeficiency patients. Methods Common variable immunodeficiency patients (n = 24) and healthy controls (n = 23) evaluated for chitotriosidase activity with other inflammation markers (hsCRP, myeloperoxidase, serum amyloid A, ferritin), lipid profile and echocardiographic findings (carotid artery intima media thickness - cIMT, brachial artery flow-mediated vazodilatation - FMD%). Results In patients, the mean chitotriosidase activity (8.98 ± 6.28) was significantly higher than the controls (5.17 ± 3.42) ( P = 0.014). Chitotriosidase showed positive relation with hs-CRP ( P = 0.011) and SAA ( P = 0.011) but had no relation with ferritin ( P = 0.155), HDL ( P = 0.152) or LDL-cholesterol ( P = 0.380). Mean cIMT increased in patients compared with the controls ( P variable immunodeficiency patients demonstrated in vivo the presence of activated macrophages indicating ongoing inflammation. Echocardiographic diastolic functional deficiency, increased cIMT and decreased FMD% may be accepted as early atherosclerotic findings, but none of them showed relationship with chitotriosidase activities.

  13. DNA damage in nasal and brain tissues of canines exposed to air pollutants is associated with evidence of chronic brain inflammation and neurodegeneration.

    Science.gov (United States)

    Calderón-Garcidueñas, Lilian; Maronpot, Robert R; Torres-Jardon, Ricardo; Henríquez-Roldán, Carlos; Schoonhoven, Robert; Acuña-Ayala, Hilda; Villarreal-Calderón, Anna; Nakamura, Jun; Fernando, Reshan; Reed, William; Azzarelli, Biagio; Swenberg, James A

    2003-01-01

    Acute, subchronic, or chronic exposures to particulate matter (PM) and pollutant gases affect people in urban areas and those exposed to fires, disasters, and wars. Respiratory tract inflammation, production of mediators of inflammation capable of reaching the brain, systemic circulation of PM, and disruption of the nasal respiratory and olfactory barriers are likely in these populations. DNA damage is crucial in aging and in age-associated diseases such as Alzheimer's disease. We evaluated apurinic/apyrimidinic (AP) sites in nasal and brain genomic DNA, and explored by immunohistochemistry the expression of nuclear factor NFkappaB p65, inducible nitric oxide synthase (iNOS), cyclo-oxygenase 2 (COX2), metallothionein I and II, apolipoprotein E, amyloid precursor protein (APP), and beta-amyloid(1-42) in healthy dogs naturally exposed to urban pollution in Mexico City. Nickel (Ni) and vanadium (V) were measured by inductively coupled plasma mass spectrometry (ICP-MS). Forty mongrel dogs, ages 7 days-10 years were studied (14 controls from Tlaxcala and 26 exposed to urban pollution in South West Metropolitan Mexico City (SWMMC)). Nasal respiratory and olfactory epithelium were found to be early pollutant targets. Olfactory bulb and hippocampal AP sites were significantly higher in exposed than in control age matched animals. Ni and V were present in a gradient from olfactory mucosa > olfactory bulb > frontal cortex. Exposed dogs had (a) nuclear neuronal NFkappaB p65, (b) endothelial, glial and neuronal iNOS, (c) endothelial and glial COX2, (d) ApoE in neuronal, glial and vascular cells, and (e) APP and beta amyloid(1-42) in neurons, diffuse plaques (the earliest at age 11 months), and in subarachnoid blood vessels. Increased AP sites and the inflammatory and stress protein brain responses were early and significant in dogs exposed to urban pollution. Oil combustion PM-associated metals Ni and V were detected in the brain. There was an acceleration of Alzheimer

  14. Fructus mume Ethanol Extract Prevents Inflammation and Normalizes the Septohippocampal Cholinergic System in a Rat Model of Chronic Cerebral Hypoperfusion

    OpenAIRE

    Kim, Min-Soo; Bang, Ji Hye; Lee, Jun; Han, Jung-Soo; Kang, Hyung Won; Jeon, Won Kyung

    2016-01-01

    Abstract Fructus mume (F. mume), the unripe fruit of Prunus mume, has long been used in Asian countries to treat cough and chronic diarrhea. We previously reported that F. mume exerts anti-inflammatory effects in a model of chronic cerebral hypoperfusion (CCH), a key etiological factor of vascular dementia (VaD). The present study was performed to investigate the protective effects of an ethanolic extract of F. mume on the inflammatory response and cholinergic dysfunction in a model of CCH in...

  15. The effects of Jiao-Tai-Wan on sleep, inflammation and insulin resistance in obesity-resistant rats with chronic partial sleep deprivation.

    Science.gov (United States)

    Zou, Xin; Huang, Wenya; Lu, Fuer; Fang, Ke; Wang, Dingkun; Zhao, Shuyong; Jia, Jiming; Xu, Lijun; Wang, Kaifu; Wang, Nan; Dong, Hui

    2017-03-23

    Jiao-Tai-Wan (JTW), composed of Rhizome Coptidis and Cortex Cinnamomi, is a classical traditional Chinese prescription for treating insomnia. Several in vivo studies have concluded that JTW could exert its therapeutical effect in insomnia rats. However, the specific mechanism is still unclear. The present study aimed to explore the effect of JTW on sleep in obesity-resistant (OR) rats with chronic partial sleep deprivation (PSD) and to clarify its possible mechanism. JTW was prepared and the main components contained in the granules were identified by 3D-High Performance Liquid Chromatography (3D-HPLC) assay. The Male Sprague-Dawley (SD) rats underwent 4 h PSD by environmental noise and the treatment with low and high doses of JTW orally for 4 weeks, respectively. Then sleep structure was analyzed by electroencephalographic (EEG). Inflammation markers including high-sensitivity C reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels were examined in the rat plasma. Meanwhile, metabolic parameters as body weight increase rate, fasting plasma glucose (FPG), fasting insulin (FINS) levels and insulin resistance index (HOMA-IR) were measured. The expressions of clock gene cryptochromes (Cry1 and Cry2) and inflammation gene nuclear factor-κB (NF-κB) in peripheral blood monocyte cells (PBMC) were also determined. The result showed that the administration of JTW significantly increased total sleep time and total slow wave sleep (SWS) time in OR rats with PSD. Furthermore, the treatment with JTW reversed the increase in the markers of systemic inflammation and insulin resistance caused by sleep loss. These changes were also associated with the up-regulation of Cry1 mRNA and Cry 2 mRNA and the down-regulation of NF-κB mRNA expression in PBMC. This study suggests that JTW has the beneficial effects of improving sleep, inflammation and insulin sensitivity. The mechanism appears to be related to the modulation of circadian clock and

  16. Tryptophan metabolism, its relation to inflammation and stress markers and association with psychological and cognitive functioning: Tasmanian Chronic Kidney Disease pilot study.

    Science.gov (United States)

    Karu, Naama; McKercher, Charlotte; Nichols, David S; Davies, Noel; Shellie, Robert A; Hilder, Emily F; Jose, Matthew D

    2016-11-10

    Adults with chronic kidney disease (CKD) exhibit alterations in tryptophan metabolism, mainly via the kynurenine pathway, due to higher enzymatic activity induced mainly by inflammation. Indoles produced by gut-microflora are another group of tryptophan metabolites related to inflammation and conditions accompanying CKD. Disruptions in tryptophan metabolism have been associated with various neurological and psychological disorders. A high proportion of CKD patients self-report symptoms of depression and/or anxiety and decline in cognitive functioning. This pilot study examines tryptophan metabolism in CKD and explores associations with psychological and cognitive functioning. Twenty-seven adults with CKD were part of 49 patients recruited to participate in a prospective pilot study, initially with an eGFR of 15-29 mL/min/1.73 m 2 . Only participants with viable blood samples and complete psychological/cognitive data at a 2-year follow-up were included in the reported cross-sectional study. Serum samples were analysed by Liquid Chromatography coupled to Mass Spectrometry, for tryptophan, ten of its metabolites, the inflammation marker neopterin and the hypothalamic-pituitary-adrenal (HPA) axis marker cortisol. The tryptophan breakdown index (kynurenine / tryptophan) correlated with neopterin (Pearson R = 0.51 P = 0.006) but not with cortisol. Neopterin levels also correlated with indoxyl sulfate (R = 0.68, P tryptophan (R range 0.5-0.7, all P ≤ 0.01), which were all negatively related to eGFR (P tryptophan breakdown via the kynurenine pathway, yet without sparing tryptophan metabolism through the 5-HT (serotonin) pathway in CKD patients. The multiple moderate associations between indole-3 acetic acid and psychological measures were a novel finding. The presented pilot data necessitate further exploration of these associations within a large prospective cohort to assess the broader significance of these findings.

  17. Modulation of monocyte/macrophage-derived cytokine and chemokine profile by persistent Hepatitis C virus (HCV infection leads to chronic inflammation

    Directory of Open Access Journals (Sweden)

    Penelope Mavromara

    2012-02-01

    Full Text Available HCV infection presents a major public health problem, with more than 170 million people infected worldwide. Chronicity and persistence of infection constitute the hallmark of the disease. Although HCV is a hepatotropic virus, subsets of immune cells have been found to be permissive to infection and viral replication. Peripheral blood monocytes, attracted to the site of infection and differentiated into macrophages, and resident hepatic macrophages, known as Kupffer cells, are important mediators of innate immunity, through production of several chemokines and cytokines in addition to their phagocytic activity. HCV proteins have been shown to modulate the cytokine and chemokine production profile of monocytes/macrophages, as it is suggested by both in vitro and clinical studies. This modified expression profile appears crucial for the establishment of aberrant inflammation that leads to liver cirrhosis and hepatocellular carcinoma.

  18. Endogenous osteopontin induces myocardial CCL5 and MMP-2 activation that contributes to inflammation and cardiac remodeling in a mouse model of chronic Chagas heart disease.

    Science.gov (United States)

    Caballero, Eugenia Pérez; Santamaría, Miguel H; Corral, Ricardo S

    2018-01-01

    Cardiac dysfunction with progressive inflammation and fibrosis is a hallmark of Chagas disease caused by persistent Trypanosoma cruzi infection. Osteopontin (OPN) is a pro-inflammatory cytokine that orchestrates mechanisms controlling cell recruitment and cardiac architecture. Our main goal was to study the role of endogenous OPN as a modulator of myocardial CCL5 chemokine and MMP-2 metalloproteinase, and its pathological impact in a murine model of Chagas heart disease. Wild-type (WT) and OPN-deficient (spp1 -/-) mice were parasite-infected (Brazil strain) for 100days. Both groups developed chronic myocarditis with similar parasite burden and survival rates. However, spp1 -/- infection showed lower heart-to-body ratio (PChagas heart disease, through the upregulation of myocardial CCL5/MMP-2 expression and activities resulting in pro-inflammatory and pro-hypertrophic events, cardiac remodeling and interstitial fibrosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Quercetin along with piperine prevents cognitive dysfunction, oxidative stress and neuro-inflammation associated with mouse model of chronic unpredictable stress.

    Science.gov (United States)

    Rinwa, Puneet; Kumar, Anil

    2017-10-01

    Stress occurs in everyday life and persistence of it causes memory loss. Bioflavonoids like quercetin are reported to have poor bioavailability and limited therapeutic potential against stress induced neurological disorders. Therefore, the present study is an attempt to elucidate the therapeutic potency of combination of quercetin with piperine; a bioavailability enhancer against chronic unpredictable stress (CUS)-induced behavioral and biochemical alterations. Laca mice were subjected to a series of stressful events for a period of 28 days. Quercetin (20, 40 and 80 mg/kg, p.o.), piperine (20 mg/kg, p.o.) and their combinations were administered daily 30 min before CUS procedure. Piracetam (100 mg/kg, i.p.) served as a standard control. CUS caused impaired spatial navigation in Morris water maze test and poor retention in elevated plus maze task. Further, there was significant increase in brain oxidative stress markers and neuro-inflammation (TNF-α). This was coupled with marked rise in acetylcholinesterase and serum corticosterone levels. Co-administration of piperine with quercetin significantly elevated their potential to restore these behavioral, biochemical and molecular changes associated with mouse model of CUS. These results suggest that piperine enhances the neuroprotective effects of quercetin against CUS-induced oxidative stress, neuro-inflammation and memory deficits.

  20. Chronic obstructive pulmonary disease and asthma-associated Proteobacteria, but not commensal Prevotella spp., promote Toll-like receptor 2-independent lung inflammation and pathology.

    Science.gov (United States)

    Larsen, Jeppe M; Musavian, Hanieh S; Butt, Tariq M; Ingvorsen, Camilla; Thysen, Anna H; Brix, Susanne

    2015-02-01

    Recent studies of healthy human airways have revealed colonization by a distinct commensal bacterial microbiota containing Gram-negative Prevotella spp. However, the immunological properties of these bacteria in the respiratory system remain unknown. Here we compare the innate respiratory immune response to three Gram-negative commensal Prevotella strains (Prevotella melaninogenica, Prevotella nanceiensis and Prevotella salivae) and three Gram-negative pathogenic Proteobacteria known to colonize lungs of patients with chronic obstructive pulmonary disease (COPD) and asthma (Haemophilus influenzae B, non-typeable Haemophilus influenzae and Moraxella catarrhalis). The commensal Prevotella spp. and pathogenic Proteobacteria were found to exhibit intrinsic differences in innate inflammatory capacities on murine lung cells in vitro. In vivo in mice, non-typeable H. influenzae induced severe Toll-like receptor 2 (TLR2)-independent COPD-like inflammation characterized by predominant airway neutrophilia, expression of a neutrophilic cytokine/chemokine profile in lung tissue, and lung immunopathology. In comparison, P. nanceiensis induced a diminished neutrophilic airway inflammation and no detectable lung pathology. Interestingly, the inflammatory airway response to the Gram-negative bacteria P. nanceiensis was completely TLR2-dependent. These findings demonstrate weak inflammatory properties of Gram-negative airway commensal Prevotella spp. that may make colonization by these bacteria tolerable by the respiratory immune system. © 2014 John Wiley & Sons Ltd.

  1. Chronic intermittent hypobaric hypoxia attenuates monocrotaline-induced pulmonary arterial hypertension via modulating inflammation and suppressing NF-κB /p38 pathway

    Directory of Open Access Journals (Sweden)

    Lei Gao

    2018-03-01

    Full Text Available Objective(s: Inflammation is involved in various forms of pulmonary arterial hypertension (PAH. Although the pathophysiology of PAH remains uncertain, NF-κB and p38 mitogen-activated protein kinase (p38 MAPK has been reportedto be associated with many inflammatory mediators of PAH. This study aimed to evaluate the effect of chronic intermittent hypobaric hypoxia (CIHH on pulmonary inflammation and remodeling in monocrotaline (MCT induced PAH in rats. Materials and Methods: An in vivo model of PAH induced by MCT was employed. Statistical analyses were assessed bydone using one-way analysis of variance (ANOVA or Fisher's LSD test for multiple comparisons. Results: Four weeks of CIHH exposure following MCT injection resulted in significant reduction of mean pulmonary artery pressure (mPAP level and improvement of right ventricular hypertrophy (RVH. Morphometric analyses showed decreased wall thickness of pulmonary arterioles in MCT+CIHH treated rats. These findings are consistent with the decrease in Ki-67 immunostaining. Following CIHH treatments, apoptotic analysis showed a consistent decrease in T lymphocytes together with lower levels of CD4+ T cell subset as measured in spleen and blood samples. Furthermore, CIHH treatment resulted in markedly reduced expression of TNF-α and IL-6 via the inhibition of NF-κB and p38 MAPK activity in rat lungs. Conclusion: Altogether, these results provide new evidence relating to the mode of action of CIHH in the prevention of PAH induced by MCT.

  2. Is there a role for diet in ameliorating the reproductive sequelae associated with chronic low-grade inflammation in polycystic ovary syndrome and obesity?

    Science.gov (United States)

    Riley, Joan K; Jungheim, Emily S

    2016-09-01

    A 2013 ASRM committee opinion titled "Optimizing natural fertility" stated that "there is little evidence that dietary variations such as vegetarian diets, low-fat diets, vitamin-enriched diets, antioxidants, or herbal remedies improve fertility …." However, there are emerging epidemiologic data demonstrating that certain components of the diet may influence reproductive health outcomes. Furthermore, translational work with human specimens and animal models lends biologic plausibility to the epidemiologic data, particularly in the context of female reproductive diseases associated with inflammation, including polycystic ovary syndrome (PCOS) and obesity. How to best apply these data clinically for improved reproductive outcomes remains to be determined. In this review, we outline a role for chronic inflammation in the reproductive sequelae of PCOS and obesity and we summarize epidemiologic and translational work demonstrating a potential role for diet in the regulation of inflammatory processes associated with these disorders. These studies identify areas for future research and potential clinical intervention in women affected by the reproductive sequelae of PCOS and obesity. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  3. Gut Microbiota Mediates the Protective Effects of Dietary Capsaicin against Chronic Low-Grade Inflammation and Associated Obesity Induced by High-Fat Diet

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    Chao Kang

    2017-05-01

    Full Text Available Metabolic endotoxemia originating from dysbiotic gut microbiota has been identified as a primary mediator for triggering the chronic low-grade inflammation (CLGI responsible for the development of obesity. Capsaicin (CAP is the major pungent bioactivator in chili peppers and has potent anti-obesity functions, yet the mechanisms linking this effect to gut microbiota remain obscure. Here we show that mice fed a high-fat diet (HFD supplemented with CAP exhibit lower levels of metabolic endotoxemia and CLGI associated with lower body weight gain. High-resolution responses of the microbiota were examined by 16S rRNA sequencing, short-chain fatty acid (SCFA measurements, and phylogenetic reconstruction of unobserved states (PICRUSt analysis. The results showed, among others, that dietary CAP induced increased levels of butyrate-producing Ruminococcaceae and Lachnospiraceae, while it caused lower levels of members of the lipopolysaccharide (LPS-producing family S24_7. Predicted function analysis (PICRUSt showed depletion of genes involved in bacterial LPS synthesis in response to CAP. We further identified that inhibition of cannabinoid receptor type 1 (CB1 by CAP also contributes to prevention of HFD-induced gut barrier dysfunction. Importantly, fecal microbiota transplantation experiments conducted in germfree mice demonstrated that dietary CAP-induced protection against HFD-induced obesity is transferrable. Moreover, microbiota depletion by a cocktail of antibiotics was sufficient to block the CAP-induced protective phenotype against obesity, further suggesting the role of microbiota in this context. Together, our findings uncover an interaction between dietary CAP and gut microbiota as a novel mechanism for the anti-obesity effect of CAP acting through prevention of microbial dysbiosis, gut barrier dysfunction, and chronic low-grade inflammation.

  4. Low-fat yogurt consumption reduces biomarkers of chronic inflammation and inhibits markers of endotoxin exposure in healthy premenopausal women: a randomised controlled trial.

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    Pei, Ruisong; DiMarco, Diana M; Putt, Kelley K; Martin, Derek A; Gu, Qinlei; Chitchumroonchokchai, Chureeporn; White, Heather M; Scarlett, Cameron O; Bruno, Richard S; Bolling, Bradley W

    2017-12-01

    The anti-inflammatory mechanisms of low-fat dairy product consumption are largely unknown. The objective of this study was to determine whether low-fat yogurt reduces biomarkers of chronic inflammation and endotoxin exposure in women. Premenopausal women (BMI 18·5-27 and 30-40 kg/m2) were randomised to consume 339 g of low-fat yogurt (yogurt non-obese (YN); yogurt obese (YO)) or 324 g of soya pudding (control non-obese; control obese (CO)) daily for 9 weeks (n 30/group). Fasting blood samples were analysed for IL-6, TNF-α/soluble TNF II (sTNF-RII), high-sensitivity C-reactive protein, 2-arachidonoyl glycerol, anandamide, monocyte gene expression, soluble CD14 (sCD14), lipopolysaccharide (LPS), LPS binding protein (LBP), IgM endotoxin-core antibody (IgM EndoCAb), and zonulin. BMI, waist circumference and blood pressure were also determined. After 9-week yogurt consumption, YO and YN had decreased TNF-α/sTNFR-RII. Yogurt consumption increased plasma IgM EndoCAb regardless of obesity status. sCD14 was not affected by diet, but LBP/sCD14 was lowered by yogurt consumption in both YN and YO. Yogurt intervention increased plasma 2-arachidonoylglycerol in YO but not YN. YO peripheral blood mononuclear cells expression of NF-κB inhibitor α and transforming growth factor β1 increased relative to CO at 9 weeks. Other biomarkers were unchanged by diet. CO and YO gained approximately 0·9 kg in body weight. YO had 3·6 % lower diastolic blood pressure at week 3. Low-fat yogurt for 9 weeks reduced biomarkers of chronic inflammation and endotoxin exposure in premenopausal women compared with a non-dairy control food. This trial was registered as NCT01686204.

  5. Determination of oxidative stress and cellular inflammation in patients with diabetic nephropathy and non-diabetic nephropathy being administered hemodialysis treatment due to chronic renal failure.

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    Avci, Emre; Cakir, Erdinc; Cevher, Sule Coskun; Yaman, Halil; Agilli, Mehmet; Bilgi, Cumhur

    2014-06-01

    We aimed to evaluate oxidative stress [8-hydroxydeoxyguanosine (8-OHdG), malondialdehyde (MDA)] endothelial damage [asymmetric dimethylarginine (ADMA)] and markers of cellular inflammation [interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), neopterin (NP) and high-sensitivity C-reactive protein (hsCRP)] in patients with diabetic nephropathy (DN) and non-diabetic nephropathy who were being administered hemodialysis treatment because of chronic renal failure. In determining 8-OHdG, IL-6 and TNF-α levels, Enzyme-Linked Immuno-Sorbent Assay method was used. Serum MDA, ADMA and NP levels were determined by using high performance liquid chromatography (HPLC). And hs-CRP values were measured with nephelometric method. Serum 8-OHdG and MDA levels were found statistically to have increased when compared with those of the control group in patients groups after dialysis. However, serum ADMA and neopterin levels were observed statistically to have decreased when compared with those of the control group in patients groups after dialysis. But, decreases on ADMA and neopterin levels are still much higher than those of control. IL-6 and TNF-α levels were found to have increased when compared with those of control group in patients groups before dialysis. The oxidative stress in patients with DN, who were being treated with hemodialysis due to chronic renal failure, was higher than that of non-DN patients who were being treated with hemodialysis. In contrast with this, inflammation occurring in non-DN patients was found to have been higher than that of in patients with DN.

  6. The silencing of cathepsin K used in gene therapy for periodontal disease reveals the role of cathepsin K in chronic infection and inflammation.

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    Chen, W; Gao, B; Hao, L; Zhu, G; Jules, J; MacDougall, M J; Wang, J; Han, X; Zhou, X; Li, Y-P

    2016-10-01

    Periodontitis is a severe chronic inflammatory disease and one of the most prevalent non-communicable chronic diseases that affects the majority of the world's adult population. While great efforts have been devoted toward understanding the pathogenesis of periodontitis, there remains a pressing need for developing potent therapeutic strategies for targeting this dreadful disease. In this study, we utilized adeno-associated virus (AAV) expressing cathepsin K (Ctsk) small hairpin (sh)RNA (AAV-sh-Ctsk) to silence Ctsk in vivo and subsequently evaluated its impact in periodontitis as a potential therapeutic strategy for this disease. We used a known mouse model of periodontitis, in which wild-type BALB/cJ mice were infected with Porphyromonas gingivalis W50 in the maxillary and mandibular periodontium to induce the disease. AAV-sh-Ctsk was then administrated locally into the periodontal tissues in vivo, followed by analyses to assess progression of the disease. AAV-mediated Ctsk silencing drastically protected mice (> 80%) from P. gingivalis-induced bone resorption by osteoclasts. In addition, AAV-sh-Ctsk administration drastically reduced inflammation by impacting the expression of many inflammatory cytokines as well as T-cell and dendritic cell numbers in periodontal lesions. AAV-mediated Ctsk silencing can simultaneously target both the inflammation and bone resorption associated with periodontitis through its inhibitory effect on immune cells and osteoclast function. Thereby, AAV-sh-Ctsk administration can efficiently protect against periodontal tissue damage and alveolar bone loss, establishing this AAV-mediated local silencing of Ctsk as an important therapeutic strategy for effectively treating periodontal disease. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Functional characterization of a competitive peptide antagonist of p65 in human macrophage-like cells suggests therapeutic potential for chronic inflammation

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    Srinivasan M

    2014-12-01

    Full Text Available Mythily Srinivasan,1 Corinne Blackburn,1 Debomoy K Lahiri2,3 1Department of Oral Pathology, Medicine and Radiology, Indiana University School of Dentistry, 2Institute of Psychiatry Research, Department of Psychiatry, 3Department of Medical and Molecular Genetics, School of Medicine, Indiana University-Purdue University, Indianapolis, IN, USA Abstract: Glucocorticoid-induced leucine zipper (GILZ is a glucocorticoid responsive protein that links the nuclear factor-kappa B (NFκB and the glucocorticoid signaling pathways. Functional and binding studies suggest that the proline-rich region at the carboxy terminus of GILZ binds the p65 subunit of NFκB and suppresses the immunoinflammatory response. A widely-used strategy in the discovery of peptide drugs involves exploitation of the complementary surfaces of naturally occurring binding partners. Previously, we observed that a synthetic peptide (GILZ-P derived from the proline-rich region of GILZ bound activated p65 and ameliorated experimental encephalomyelitis. Here we characterize the secondary structure of GILZ-P by circular dichroic analysis. GILZ-P adopts an extended polyproline type II helical conformation consistent with the structural conformation commonly observed in interfaces of transient intermolecular interactions. To determine the potential application of GILZ-P in humans, we evaluated the toxicity and efficacy of the peptide drug in mature human macrophage-like THP-1 cells. Treatment with GILZ-P at a wide range of concentrations commonly used for peptide drugs was nontoxic as determined by cell viability and apoptosis assays. Functionally, GILZ-P suppressed proliferation and glutamate secretion by activated macrophages by inhibiting nuclear translocation of p65. Collectively, our data suggest that the GILZ-P has therapeutic potential in chronic CNS diseases where persistent inflammation leads to neurodegeneration such as multiple sclerosis and Alzheimer’s disease. Keywords

  8. Liver FOXP3 and PD1/PDL1 expression is down-regulated in chronic HBV hepatitis on maintained remission related to the degree of inflammation

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    Georgios eGermanidis

    2013-07-01

    Full Text Available Background & aim: T-cell expression of PD1 and inhibition of T effector cells by Foxp3+-T regulatory cells are among the most powerful mechanisms for achieving a balanced immune response. Our aim was to investigate, how liver FOXP3 and PD1/PDL1 expression is regulated in chronic HBV hepatitis (CHB on maintained long-term remission in comparison with active disease, and whether they are correlated to the expression of pro- and anti-inflammatory cytokines and apoptosis mediators, along with the degree of histological inflammation and markers of T-cell effector restoration. Methods: Fifty-three HBeAg-negative CHB patients with both active (30 and completely remitted disease on long-term antiviral treatment (23 and 4 controls (submitted to liver biopsy due to a mild increase of aminotransferases but without liver necroinflammatory and architecture changes were enrolled in the study. Liver mRNA levels of immunoregulatory genes (FOXP3, IL10, TGFB1, and those of PD1/PDL1/PDL2 pathway, major apoptosis mediators (FAS, FASL, TNFA, TRAIL, cytokines of effector T-cell restoration (IL2, IFNG, and those of IL1B, CD4 and CD8, were evaluated by qRT-PCR and were correlated with each other, along with the intensity of liver inflammation and fibrosis staging. The expression and localization of FOXP3, PD1, PDL1, CD4, and CD8 were also assessed by immunohistochemistry. Results: The expression of FOXP3, IL10, TGFB1, PD1, PDL1, FASL, and CD8 was significantly down-regulated in the remission state. In contrast, liver expression of IL2 and IFNG, along with CD4, IL1B, TNFA and FAS did not change significantly. Moreover, FOXP3, PD1, PDL1, and CD8 transcripts were positively correlated to the intensity of liver inflammation. Conclusion: Our data indicate that in the CHB disease model, the immunosuppressive liver environment is down-regulated in the maintained on-treatment long-term remission state and correlates with the intensity of liver inflammation, but not liver T

  9. Monocyte chemotactic protein-1 (MCP-1 in patients with chronic schistosomiasis mansoni: evidences of subclinical renal inflammation.

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    Ana Lúcia P Hanemann

    Full Text Available The aim of this study is to investigate renal markers and the biomarker MCP-1 in patients with schistosomiasis mansoni. This is a cross-sectional study with 85 patients aged 5 to 48 years, with a confirmed diagnosis of schistosomiasis mansoni through the Kato-Katz method. The patients were divided in three groups: control (G-I; infected by S. mansoni before treatment (G-II and infected by S. mansoni after treatment (G-III. Renal function was evaluated by tubular and glomerular biomarkers and through urinary MCP-1. Patients' mean age was 23.2 ± 13 years. There was no statistically significant difference between the groups regarding tubular and glomerular function evaluated through the traditional biomarkers. MCP-1 was higher in G-II and G-III, when compared to G-I; p=0.009 and p=0.007, respectively. There was no difference when comparing groups G-II and G-III (p=0.892. Although it was not different among the groups, there was a significant correlation between albuminuria and MCP-1. There was a significant increase in urinary MCP-1 levels in patients with schistosomiasis mansoni, which was associated with albuminuria. This protein has a role in the recruitment of monocytes to injury and inflammation sites . The increase of MCP-1 in the urine evidences that there is silent renal inflammation in these patients and the inflammatory status is not interrupted by specific treatment of the offending agent. Our findings suggest that urinary MCP-1 can be a sensitive marker of renal injury in patients with schistosomiasis mansoni.

  10. Inhalation of honey reduces airway inflammation and histopathological changes in a rabbit model of ovalbumin-induced chronic asthma

    Science.gov (United States)

    2014-01-01

    Background Honey is widely used in folk medicine to treat cough, fever, and inflammation. In this study, the effect of aerosolised honey on airway tissues in a rabbit model of ovalbumin (OVA)-induced asthma was investigated. The ability of honey to act either as a rescuing agent in alleviating asthma-related symptoms or as a preventive agent to preclude the occurrence of asthma was also assessed. Methods Forty New Zealand white rabbits were sensitized twice with mixture of OVA and aluminium hydroxide on days 1 and 14. Honey treatments were given from day 23 to day 25 at two different doses (25% (v/v) and 50% (v/v) of honey diluted in sterile phosphate buffer saline. In the aerosolised honey as a rescue agent group, animals were euthanized on day 28; for the preventive group, animals were further exposed to aerosolised OVA for 3 days starting from day 28 and euthanized on day 31. The effects of honey on inflammatory cell response, airway inflammation, and goblet cell hyperplasia were assessed for each animal. Results Histopathological analyses revealed that aerosolised honey resulted in structural changes of the epithelium, mucosa, and submucosal regions of the airway that caused by the induction with OVA. Treatment with aerosolised honey has reduced the number of airway inflammatory cells present in bronchoalveolar lavage fluid and inhibited the goblet cell hyperplasia. Conclusion In this study, aerosolised honey was used to effectively treat and manage asthma in rabbits, and it could prove to be a promising treatment for asthma in humans. Future studies with a larger sample size and studies at the gene expression level are needed to better understand the mechanisms by which aerosolised honey reduces asthma symptoms. PMID:24886260

  11. Acute and Chronic Toxicity, Cytochrome P450 Enzyme Inhibition, and hERG Channel Blockade Studies with a Polyherbal, Ayurvedic Formulation for Inflammation

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    Debendranath Dey

    2015-01-01

    Full Text Available Ayurvedic plants are known for thousands of years to have anti-inflammatory and antiarthritic effect. We have recently shown that BV-9238, a proprietary formulation of Withania somnifera, Boswellia serrata, Zingiber officinale, and Curcuma longa, inhibits LPS-induced TNF-alpha and nitric oxide production from mouse macrophage and reduces inflammation in different animal models. To evaluate the safety parameters of BV-9238, we conducted a cytotoxicity study in RAW 264.7 cells (0.005–1 mg/mL by MTT/formazan method, an acute single dose (2–10 g/kg bodyweight toxicity study and a 180-day chronic study with 1 g and 2 g/kg bodyweight in Sprague Dawley rats. Some sedation, ptosis, and ataxia were observed for first 15–20 min in very high acute doses and hence not used for further chronic studies. At the end of 180 days, gross and histopathology, blood cell counts, liver and renal functions were all at normal levels. Further, a modest attempt was made to assess the effects of BV-9238 (0.5 µg/mL on six major human cytochrome P450 enzymes and 3H radioligand binding assay with human hERG receptors. BV-9238 did not show any significant inhibition of these enzymes at the tested dose. All these suggest that BV-9238 has potential as a safe and well tolerated anti-inflammatory formulation for future use.

  12. Fructus mume Ethanol Extract Prevents Inflammation and Normalizes the Septohippocampal Cholinergic System in a Rat Model of Chronic Cerebral Hypoperfusion.

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    Kim, Min-Soo; Bang, Ji Hye; Lee, Jun; Han, Jung-Soo; Kang, Hyung Won; Jeon, Won Kyung

    2016-02-01

    Fructus mume (F. mume), the unripe fruit of Prunus mume, has long been used in Asian countries to treat cough and chronic diarrhea. We previously reported that F. mume exerts anti-inflammatory effects in a model of chronic cerebral hypoperfusion (CCH), a key etiological factor of vascular dementia (VaD). The present study was performed to investigate the protective effects of an ethanolic extract of F. mume on the inflammatory response and cholinergic dysfunction in a model of CCH induced by bilateral common carotid artery occlusion (BCCAo) in Wistar rats. Rats were assigned to three treatment groups: sham plus vehicle, BCCAo plus vehicle, and BCCAo plus F. mume extract (200 mg/kg). F. mume was administered by oral gavage from days 21 to 42 following BCCAo. Glial cell numbers were measured in the white matter and hippocampus. The hippocampal expressions of proinflammatory cytokines, angiotensin-II (Ang-II), receptor for advanced glycation end products (RAGE), and mitogen-activated protein kinase (MAPKs) were also evaluated. Choline acetyltransferase (ChAT) levels in the hippocampus and basal forebrain were examined. Rats with BCCAo showed an increase in the number of glial cells and levels of proinflammatory cytokines, Ang-II, RAGE, and MAPKs, all of which were significantly attenuated by F. mume treatment. F. mume administration also restored ChAT expression in the basal forebrain and hippocampus following chronic BCCAo. These results suggest that F. mume is a potentially valuable drug or nutraceutical for the treatment of VaD.

  13. Enalapril in Combination with Benznidazole Reduces Cardiac Inflammation and Creatine Kinases in Mice Chronically Infected with Trypanosoma cruzi

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    Penitente, Arlete Rita; Leite, Ana Luísa Junqueira; de Paula Costa, Guilherme; Shrestha, Deena; Horta, Aline Luciano; Natali, Antônio J.; Neves, Clóvis A.; Talvani, Andre

    2015-01-01

    The protozoan Trypanosoma cruzi triggers an inflammatory process in mammalian heart causing events such as fibrosis, changes in the architecture and functionality in this organ. Enalapril, an angiotensin II-converting enzyme inhibitor, is a drug prescribed to ameliorate this heart dysfunction, and appears to exert a potential role in immune system regulation. Our aim was to evaluate the chronic cardiac inflammatory parameters after therapeutic treatment with enalapril and benznidazole in C57BL/6 mice infected with the VL-10 strain of T. cruzi. After infection, animals were treated with oral doses of enalapril (25 mg/kg), benznidazole (100 mg/kg), or both during 30 days. Morphometric parameters and levels of chemokines (CCL2, CCL5), IL-10, creatine kinases (CKs), and C-reactive protein were evaluated in the heart and serum at the 120th day of infection. Enalapril alone or in combination with benznidazole did not change the number of circulating parasites, but reduced cardiac leukocyte recruitment and total collagen in the cardiac tissue. Interestingly, the combination therapy (enalapril/benznidazole) also reduced the levels of chemokines, CK and CK-MB, and C-reactive proteins in chronic phase. In conclusion, during the chronic experimental T. cruzi infection, the combination therapy using enalapril plus benznidazole potentiated their immunomodulatory effects, resulting in a low production of biomarkers of cardiac lesions. PMID:26350447

  14. Congenital Vomer Agenesis: A Rare and Poorly Understood Condition Revealed by Cone Beam CT.

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    Yan, David Jun; Lenoir, Vincent; Chatelain, Sibylle; Stefanelli, Salvatore; Becker, Minerva

    2018-02-10

    Isolated congenital vomer agenesis is a very rare and poorly understood condition. In the context of dental work-up by cone-beam computed tomography (CBCT), the explored volume of the facial bones occasionally reveals incidental abnormalities. We report the case of a 13-year old Caucasian female who underwent CBCT for the pre-treatment evaluation of primary failure of tooth eruption affecting the permanent right upper and inferior molars. CBCT depicted a large defect of the postero-inferior part of the nasal septum without associated soft tissue abnormality and without cranio-facial malformation or cleft palate. In the absence of a history of trauma, chronic inflammatory sinonasal disease, neoplasia and drug abuse, a posterior nasal septum defect warrants the diagnosis of vomer agenesis. A discussion of this condition and of salient CBCT features is provided.

  15. Chronic sleep restriction promotes brain inflammation and synapse loss, and potentiates memory impairment induced by amyloid-β oligomers in mice.

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    Kincheski, Grasielle C; Valentim, Isabela S; Clarke, Julia R; Cozachenco, Danielle; Castelo-Branco, Morgana T L; Ramos-Lobo, Angela M; Rumjanek, Vivian M B D; Donato, José; De Felice, Fernanda G; Ferreira, Sergio T

    2017-08-01

    It is increasingly recognized that sleep disturbances and Alzheimer's disease (AD) share a bidirectional relationship. AD patients exhibit sleep problems and alterations in the regulation of circadian rhythms; conversely, poor quality of sleep increases the risk of development of AD. The aim of the current study was to determine whether chronic sleep restriction potentiates the brain impact of amyloid-β oligomers (AβOs), toxins that build up in AD brains and are thought to underlie synapse damage and memory impairment. We further investigated whether alterations in levels of pro-inflammatory mediators could play a role in memory impairment in sleep-restricted mice. We found that a single intracerebroventricular (i.c.v.) infusion of AβOs disturbed sleep pattern in mice. Conversely, chronically sleep-restricted mice exhibited higher brain expression of pro-inflammatory mediators, reductions in levels of pre- and post-synaptic marker proteins, and exhibited increased susceptibility to the impact of i.c.v. infusion of a sub-toxic dose of AβOs (1pmol) on performance in the novel object recognition memory task. Sleep-restricted mice further exhibited an increase in brain TNF-α levels in response to AβOs. Interestingly, memory impairment in sleep-restricted AβO-infused mice was prevented by treatment with the TNF-α neutralizing monoclonal antibody, infliximab. Results substantiate the notion of a dual relationship between sleep and AD, whereby AβOs disrupt sleep/wake patterns and chronic sleep restriction increases brain vulnerability to AβOs, and point to a key role of brain inflammation in increased susceptibility to AβOs in sleep-restricted mice. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Effect of Dahuang Zhechong pill combined with antiviral therapy on serum virus replication indexes as well as immunity and inflammation indexes in patients with chronic hepatitis B cirrhosis

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    Hong-Gang Huang

    2017-04-01

    Full Text Available Objective: To study the effect of Dahuang Zhechong pill combined with antiviral therapy on serum virus replication indexes as well as immunity and inflammation indexes in patients with chronic hepatitis B cirrhosis. Methods: A total of 104 patients with chronic hepatitis B cirrhosis who were treated in our hospital between May 2013 and April 2016 were selected and randomly divided into combined treatment group and western medicine treatment group who accepted Dahuang Zhechong pill combined with entecavir treatment and entecavir monotherapy respectively. Before and after treatment, the HBV-DNA loads, liver fibrosis index and immune cell levels as well as inflammatory cytokine levels were determined. Results: HBV-DNA loads of both groups of patients at 48 weeks after treatment were significantly lower than those before treatment, and the HBV-DNA loads were not significantly different between the two groups after treatment; serum HA, LN, PC-III, IV-C, IL-15, IL-16 and TGF- β1 levels as well as peripheral blood Treg cell levels of both groups at 24 weeks and 48 weeks after treatment were significantly lower than those before treatment while peripheral blood NK cell levels were higher than those before treatment, and serum HA, LN, PC-III, IV-C, IL-15, IL-16 and TGF-β1 levels as well as peripheral blood Treg cell levels of combined treatment group were significantly lower than those of western medicine treatment group while peripheral blood NK cell levels were higher than those of western medicine treatment group. Conclusion: Dahuang Zhechong pill combined with antiviral treatment of chronic hepatitis B cirrhosis can regulate the immune response and inflammatory reaction without affecting the inhibiting effect of antiviral drugs on viral replication.

  17. Effect of a wound cleansing solution on wound bed preparation and inflammation in chronic wounds: a single-blind RCT.

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    Bellingeri, A; Falciani, F; Traspedini, P; Moscatelli, A; Russo, A; Tino, G; Chiari, P; Peghetti, A

    2016-03-01

    Research into surfactant solutions for the debridement of chronic wounds suggests that surfactants may support wound bed preparation (WBP) in chronic wounds, however their efficacy has not been evaluated in randomised controlled trials (RCTs). Our aim was to assess the clinical efficacy of a propylbetaine-polihexanide (PP) solution versus normal saline (NS) solution in WBP, assessing inflammatory signs and wound size reduction in patients with pressure ulcers (PUs) or vascular leg ulcers. In a single-blinded randomised controlled trial (RCT) patients were randomly allocated to two groups and treated with either propylbetaine-polihexanide (PP) solution (Prontosan) or NS. Wounds were assessed using the Bates-Jensen wound assessment tool (BWAT). Assessments took place at inclusion (T0), day 7 (T1), day 14 (T2), day 21 (T3), and day 28 (T4). Outcomes were analysed using a two-tailed Student's t-test. A total of 289 patients were included. Both groups had similar demographics, clinical status, and wound characteristics. Data analysis showed statistically significant differences between T0 and T4 for the following outcomes: BWAT total score, p=0.0248; BWAT score for inflammatory items, p=0.03; BWAT scores for wound size reduction (p=0.049) and granulation tissue improvement (p=0.043), all in favour of PP. The assessment of pain did not show any significant difference between the two groups. The study results showed significantly higher efficacy of the PP solution versus NS solution, in reducing inflammatory signs and accelerating the healing of vascular leg ulcers and PUs. This evidence supports the update of protocols for the care of chronic wounds. The authors have no conflict of interest regarding this research. This is an investigator initiated trial. B. Braun Milano SpA kindly provided the material under investigation for both treatment groups, and paid the Ethics Committees' application fees in all participating centres.

  18. Taurine Attenuates Hepatic Inflammation in Chronic Alcohol-Fed Rats Through Inhibition of TLR4/MyD88 Signaling.

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    Lin, Chao-Jen; Chiu, Chun-Ching; Chen, Yi-Chen; Chen, Mu-Lin; Hsu, Tsai-Ching; Tzang, Bor-Show

    2015-12-01

    Accumulating evidence indicates that overconsumption of ethanol contributes in many ways to the pathogenesis of hepatic injury. Although studies indicate that taurine decreases lipogenesis, oxidative stress, and inflammatory cytokines, the protective effect of taurine against alcohol-induced liver injury is still unclear. To clarify the precise signaling involved in the beneficial effect of taurine on alcohol-induced liver injury, rats were randomly divided into four treatment groups: (1) control (Ctl), (2) alcohol (Alc), (3) Alc+taurine (Tau), and (4) Alc+silymarin (Sil). The Tau and Sil groups had lower lymphocyte infiltration and significantly lower TLR-4/MyD88 and IκB/NFκB compared to the Alc group. The inducible nitric oxide synthase (iNOS), C-reactive protein (CRP), tumor necrosis factors (TNF)-α, interleukin (IL)-6, and IL-1β were also significantly lower in the Tau and Sil groups than in the Alc group. The experimental results indicated that hepatoprotection against alcohol-induced inflammation may be mediated by decreased TLR-4/MyD88 signaling.

  19. Aloin protects against chronic alcoholic liver injury via attenuating lipid accumulation, oxidative stress and inflammation in mice.

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    Cui, Yan; Ye, Qing; Wang, Heya; Li, Yingchao; Xia, Xiuhua; Yao, Weirong; Qian, He

    2014-12-01

    The present study was designed to investigate the protective effect of aloin against alcoholic liver disease in a chronic alcohol feeding mouse model. Mice were given alcohol twice a day by intragastric administration for 11 weeks (4.0, 4.7, 5.5 g/kg bw/day for the first 3 weeks respectively, 6.3 g/kg bw/day for the following 8 weeks). Aloin (10, 30 mg/kg bw) or vehicle was given by gavage to mice after each alcohol administration. Alcohol elevated the serum transaminases alanine aminotransferase, aspartate aminotransferase, total cholesterol and triglyceride levels which were significantly attenuated by the co-administration of aloin (p aloin significantly suppressed the alcohol-dependent induction of sterol regulatory element-binding protein-1c expression (p aloin supplementation significantly inhibited the alcohol-dependent elevation of malondialdehyde and cytochrome P4502E1 expression (p aloin (p aloin may represent a novel, protective strategy against chronic alcoholic liver injury by attenuating lipid accumulation, oxidative stress and LPS-induced inflammatory response.

  20. Elevated circulating PAI-1 levels are related to lung function decline, systemic inflammation, and small airway obstruction in chronic obstructive pulmonary disease

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    Wang H

    2016-09-01

    Full Text Available Hao Wang,1,2,* Ting Yang,1,2,* Diandian Li,1,2 Yanqiu Wu,1,2 Xue Zhang,1,2 Caishuang Pang,1,2 Junlong Zhang,3 Binwu Ying,3 Tao Wang,1,2 Fuqiang Wen1,2 1Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital of Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3Department of Laboratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, People’s Republic of China *These authors contributed equally to this work Background: Plasminogen activator inhibitor-1 (PAI-1 and soluble urokinase-type plasminogen activator receptor (suPAR participate in inflammation and tissue remolding in various diseases, but their roles in chronic obstructive pulmonary disease (COPD are not yet clear. This study aimed to investigate if PAI-1 and suPAR were involved in systemic inflammation and small airway obstruction (SAO in COPD. Methods: Demographic and clinical characteristics, spirometry examination, and blood samples were obtained from 84 COPD patients and 51 healthy volunteers. Serum concentrations of PAI-1, suPAR, tissue inhibitor of metalloproteinase-1 (TIMP-1, Matrix metalloproteinase-9 (MMP-9, and C-reactive protein (CRP were detected with Magnetic Luminex Screening Assay. Differences between groups were statistically analyzed using one-way analysis of variance or chi-square test. Pearson’s partial correlation test (adjusted for age, sex, body mass index, cigarette status, and passive smoke exposure and multivariable linear analysis were used to explore the relationships between circulating PAI-1 and indicators of COPD. Results: First, we found that serum PAI-1 levels but not suPAR levels were significantly increased in COPD patients compared with healthy volunteers (125.56±51.74 ng/mL versus 102.98±36.62 ng/mL, P=0.007. Then, the

  1. Indomethacin reduces glomerular and tubular damage markers but not renal inflammation in chronic kidney disease patients: a post-hoc analysis.

    Directory of Open Access Journals (Sweden)

    Martin H de Borst

    Full Text Available Under specific conditions non-steroidal anti-inflammatory drugs (NSAIDs may be used to lower therapy-resistant proteinuria. The potentially beneficial anti-proteinuric, tubulo-protective, and anti-inflammatory effects of NSAIDs may be offset by an increased risk of (renal side effects. We investigated the effect of indomethacin on urinary markers of glomerular and tubular damage and renal inflammation. We performed a post-hoc analysis of a prospective open-label crossover study in chronic kidney disease patients (n = 12 with mild renal function impairment and stable residual proteinuria of 4.7±4.1 g/d. After a wash-out period of six wks without any RAAS blocking agents or other therapy to lower proteinuria (untreated proteinuria (UP, patients subsequently received indomethacin 75 mg BID for 4 wks (NSAID. Healthy subjects (n = 10 screened for kidney donation served as controls. Urine and plasma levels of total IgG, IgG4, KIM-1, beta-2-microglobulin, H-FABP, MCP-1 and NGAL were determined using ELISA. Following NSAID treatment, 24 h -urinary excretion of glomerular and proximal tubular damage markers was reduced in comparison with the period without anti-proteinuric treatment (total IgG: UP 131[38-513] vs NSAID 38[17-218] mg/24 h, p<0.01; IgG4: 50[16-68] vs 10[1-38] mg/24 h, p<0.001; beta-2-microglobulin: 200[55-404] vs 50[28-110] ug/24 h, p = 0.03; KIM-1: 9[5]-[14] vs 5[2]-[9] ug/24 h, p = 0.01. Fractional excretions of these damage markers were also reduced by NSAID. The distal tubular marker H-FABP showed a trend to reduction following NSAID treatment. Surprisingly, NSAID treatment did not reduce urinary excretion of the inflammation markers MCP-1 and NGAL, but did reduce plasma MCP-1 levels, resulting in an increased fractional MCP-1 excretion. In conclusion, the anti-proteinuric effect of indomethacin is associated with reduced urinary excretion of glomerular and tubular damage markers, but not with reduced excretion of renal

  2. Elevated circulating PAI-1 levels are related to lung function decline, systemic inflammation, and small airway obstruction in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Wang, Hao; Yang, Ting; Li, Diandian; Wu, Yanqiu; Zhang, Xue; Pang, Caishuang; Zhang, Junlong; Ying, Binwu; Wang, Tao; Wen, Fuqiang

    2016-01-01

    Plasminogen activator inhibitor-1 (PAI-1) and soluble urokinase-type plasminogen activator receptor (suPAR) participate in inflammation and tissue remolding in various diseases, but their roles in chronic obstructive pulmonary disease (COPD) are not yet clear. This study aimed to investigate if PAI-1 and suPAR were involved in systemic inflammation and small airway obstruction (SAO) in COPD. Demographic and clinical characteristics, spirometry examination, and blood samples were obtained from 84 COPD patients and 51 healthy volunteers. Serum concentrations of PAI-1, suPAR, tissue inhibitor of metalloproteinase-1 (TIMP-1), Matrix metalloproteinase-9 (MMP-9), and C-reactive protein (CRP) were detected with Magnetic Luminex Screening Assay. Differences between groups were statistically analyzed using one-way analysis of variance or chi-square test. Pearson's partial correlation test (adjusted for age, sex, body mass index, cigarette status, and passive smoke exposure) and multivariable linear analysis were used to explore the relationships between circulating PAI-1 and indicators of COPD. First, we found that serum PAI-1 levels but not suPAR levels were significantly increased in COPD patients compared with healthy volunteers (125.56±51.74 ng/mL versus 102.98±36.62 ng/mL, P =0.007). Then, the correlation analysis showed that circulating PAI-1 was inversely correlated with pulmonary function parameters including the ratio of forced expiratory volume in 1 second to forced vital capacity (FEV 1 /FVC), FEV 1 /Pre (justified r =-0.308, P <0.001; justified r =-0.295, P =0.001, respectively) and SAO indicators such as FEV 3 /FVC, MMEF25-75/Pre (justified r =-0.289, P =0.001; justified r =-0.273, P =0.002, respectively), but positively related to the inflammatory marker CRP (justified r =0.351, P <0.001), the small airway remolding biomarker TIMP-1, and MMP-9 (justified r =0.498, P <0.001; justified r =0.267, P =0.002, respectively). Besides, multivariable linear analysis

  3. Association of terpinolene and diclofenac presents antinociceptive and anti-inflammatory synergistic effects in a model of chronic inflammation

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    E.M.A. Macedo

    2016-01-01

    Full Text Available Pharmacological treatment of inflammatory pain is usually done by administration of non-steroidal anti-inflammatory drugs (NSAIDs. These drugs present high efficacy, although side effects are common, especially gastrointestinal lesions. One of the pharmacological strategies to minimize such effects is the combination of drugs and natural products with synergistic analgesic effect. The monoterpene terpinolene (TPL is a chemical constituent of essential oils present in many plant species, which have pharmacological activities, such as analgesic and anti-inflammatory. The association of ineffective doses of TPL and diclofenac (DCF (3.125 and 1.25 mg/kg po, respectively presented antinociceptive and anti-inflammatory effects in the acute (0, 1, 2, 3, 4, 5 and 6 h, after treatment and chronic (10 days inflammatory hyperalgesia induced by Freund's complete adjuvant (CFA in the right hind paw of female Wistar rats (170-230 g, n=6-8. The mechanical hyperalgesia was assessed by the Randall Selitto paw pressure test, which determines the paw withdrawal thresholds. The development of edema was quantified by measuring the volume of the hind paw by plethismography. The TPL/DCF association reduced neutrophils, macrophages and lymphocytes in the histological analysis of the paw, following a standard staining protocol with hematoxylin and eosin and the counts were performed with the aid of optical microscopy after chronic oral administration of these drugs. Moreover, the TPL/DCF association did not induce macroscopic gastric lesions. A possible mechanism of action of the analgesic effect is the involvement of 5-HT2A serotonin receptors, because ketanserin completely reversed the antinociceptive effect of the TPL/DCF association. These results suggest that the TPL/DCF association had a synergistic anti-inflammatory and analgesic effect without causing apparent gastric injury, and that the serotonergic system may be involved in the antinociceptive effect of this

  4. Association of terpinolene and diclofenac presents antinociceptive and anti-inflammatory synergistic effects in a model of chronic inflammation.

    Science.gov (United States)

    Macedo, E M A; Santos, W C; Sousa, B P; Lopes, E M; Piauilino, C A; Cunha, F V M; Sousa, D P; Oliveira, F A; Almeida, F R C

    2016-06-20

    Pharmacological treatment of inflammatory pain is usually done by administration of non-steroidal anti-inflammatory drugs (NSAIDs). These drugs present high efficacy, although side effects are common, especially gastrointestinal lesions. One of the pharmacological strategies to minimize such effects is the combination of drugs and natural products with synergistic analgesic effect. The monoterpene terpinolene (TPL) is a chemical constituent of essential oils present in many plant species, which have pharmacological activities, such as analgesic and anti-inflammatory. The association of ineffective doses of TPL and diclofenac (DCF) (3.125 and 1.25 mg/kg po, respectively) presented antinociceptive and anti-inflammatory effects in the acute (0, 1, 2, 3, 4, 5 and 6 h, after treatment) and chronic (10 days) inflammatory hyperalgesia induced by Freund's complete adjuvant (CFA) in the right hind paw of female Wistar rats (170-230 g, n=6-8). The mechanical hyperalgesia was assessed by the Randall Selitto paw pressure test, which determines the paw withdrawal thresholds. The development of edema was quantified by measuring the volume of the hind paw by plethismography. The TPL/DCF association reduced neutrophils, macrophages and lymphocytes in the histological analysis of the paw, following a standard staining protocol with hematoxylin and eosin and the counts were performed with the aid of optical microscopy after chronic oral administration of these drugs. Moreover, the TPL/DCF association did not induce macroscopic gastric lesions. A possible mechanism of action of the analgesic effect is the involvement of 5-HT2A serotonin receptors, because ketanserin completely reversed the antinociceptive effect of the TPL/DCF association. These results suggest that the TPL/DCF association had a synergistic anti-inflammatory and analgesic effect without causing apparent gastric injury, and that the serotonergic system may be involved in the antinociceptive effect of this association.

  5. Increased urine and serum nerve growth factor levels in interstitial cystitis suggest chronic inflammation is involved in the pathogenesis of disease.

    Directory of Open Access Journals (Sweden)

    Hsin-Tzu Liu

    Full Text Available OBJECTIVE: Interstitial cystitis/bladder pain syndrome (IC/BPS is considered a bladder disorder due to localized chronic inflammation. This study investigated the nerve growth factor (NGF levels in serum and urine in patients with IC/BPS. MATERIALS AND METHODS: Thirty patients with IC/BPS and 28 normal subjects without lower urinary tract symptoms were recruited from an outpatient clinic. IC/BPS was diagnosed by frequency, bladder pain, and the presence of glomerulations during cystoscopic hydrodistention. Serum and urine were collected before any treatment was given. Serum NGF and urinary NGF/Cr levels were compared between IC/BPS and the controls. RESULTS: Urinary NGF levels were significantly higher in patients with IC/PBS (26.3±11.2 pg/ml than in controls (1.40±0.63 pg (p = 0.014. After normalization, the urinary NGF/Cr levels were significantly greater in IC/BPS (0.69±0.38 pg/mg than controls (0.20±0.01, p = 0.011. Relative to the levels in control subjects (1.90±0.38 pg/mL, the mean serum NGF levels were higher in patients IC/BPS patients (3.48±0.55 pg/mL (p = 0.015. No significant correlation was found between the serum and urinary NGF levels in IC/BPS patients. However, the clinical characteristics and medical co-morbidities did not show significant difference between IC/BPS patients with a higher and lower serum NGF level. CONCLUSIONS: Increased urinary NGF levels in IC/BPS patients suggest that chronic inflammation is involved in this bladder disorder. Increased circulating serum NGF levels were noted in over half of patients with IC/BPS, however, the urinary and serum NGF were not inter-correlated and elevated serum NGF did not relate with clinical features.

  6. Retroperitoneal inflammation

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/001255.htm Retroperitoneal inflammation To use the sharing features on this page, please enable JavaScript. Retroperitoneal inflammation is swelling that occurs in the retroperitoneal space. ...

  7. Post-translational inhibition of IP-10 secretion in IEC by probiotic bacteria: impact on chronic inflammation.

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    Gabriele Hoermannsperger

    Full Text Available BACKGROUND: Clinical and experimental studies suggest that the probiotic mixture VSL#3 has protective activities in the context of inflammatory bowel disease (IBD. The aim of the study was to reveal bacterial strain-specific molecular mechanisms underlying the anti-inflammatory potential of VSL#3 in intestinal epithelial cells (IEC. METHODOLOGY/PRINCIPAL FINDINGS: VSL#3 inhibited TNF-induced secretion of the T-cell chemokine interferon-inducible protein (IP-10 in Mode-K cells. Lactobacillus casei (L. casei cell surface proteins were identified as active anti-inflammatory components of VSL#3. Interestingly, L. casei failed to block TNF-induced IP-10 promoter activity or IP-10 gene transcription at the mRNA expression level but completely inhibited IP-10 protein secretion as well as IP-10-mediated T-cell transmigration. Kinetic studies, pulse-chase experiments and the use of a pharmacological inhibitor for the export machinery (brefeldin A showed that L. casei did not impair initial IP-10 production but decreased intracellular IP-10 protein stability as a result of blocked IP-10 secretion. Although L. casei induced IP-10 ubiquitination, the inhibition of proteasomal or lysosomal degradation did not prevent the loss of intracellular IP-10. Most important for the mechanistic understanding, the inhibition of vesicular trafficking by 3-methyladenine (3-MA inhibited IP-10 but not IL-6 expression, mimicking the inhibitory effects of L. casei. These findings suggest that L. casei impairs vesicular pathways important for the secretion of IP-10, followed by subsequent degradation of the proinflammatory chemokine. Feeding studies in TNF(DeltaARE and IL-10(-/- mice revealed a compartimentalized protection of VSL#3 on the development of cecal but not on ileal or colonic inflammation. Consistent with reduced tissue pathology in IL-10(-/- mice, IP-10 protein expression was reduced in primary epithelial cells. CONCLUSIONS/SIGNIFICANCE: We demonstrate segment

  8. Alveolar inflammation in cystic fibrosis

    DEFF Research Database (Denmark)

    Ulrich, Martina; Worlitzsch, Dieter; Viglio, Simona

    2010-01-01

    BACKGROUND: In infected lungs of the cystic fibrosis (CF) patients, opportunistic pathogens and mutated cystic fibrosis transmembrane conductance regulator protein (CFTR) contribute to chronic airway inflammation that is characterized by neutrophil/macrophage infiltration, cytokine release...

  9. A four-step model for the IL-6 amplifier, a regulator of chronic inflammations in tissue-specific MHC class II-associated autoimmune diseases.

    Science.gov (United States)

    Murakami, Masaaki; Hirano, Toshio

    2011-01-01

    It is commonly thought that autoimmune diseases are caused by the breakdown of self-tolerance, which suggests the recognition of specific antigens by autoreactive CD4+ T cells contribute to the specificity of autoimmune diseases (Marrack et al., 2001; Mathis and Benoist, 2004). In several cases, however, even for diseases associated with class II major histocompatibility complex (MHC) alleles, the causative tissue-specific antigens recognized by memory/activated CD4+ T cells have not been established (Mocci et al., 2000; Skapenko et al., 2005). Rheumatoid arthritis (RA) and arthritis in F759 knock-in mice (F759 mice) are such examples (Atsumi et al., 2002; Brennan et al., 2002; Falgarone et al., 2009). These include associations with class II MHC and CD4 molecules; increased numbers of memory/activated CD4+ T cells; and improved outcomes in response to suppressions and/or deficiencies in class II MHC molecules, CD4+ T cells, and the T cell survival cytokine IL-7. Regarding the development of arthritis in F759 mice, it is not only the immune system, but also non-immune tissue that are involved, indicating that the importance of their interactions (Sawa et al., 2006, 2009; Ogura et al., 2008; Hirano, 2010; Murakami et al., 2011). Furthermore, we have shown that local events such as microbleeding together with an accumulation of activated CD4+ T cells in a manner independent of tissue antigen-recognitions induces arthritis in the joints of F759 mice (Murakami et al., 2011). For example, local microbleeding-mediated CCL20 expression induce such an accumulation, causing arthritis development via chronic activation of an IL-17A-dependent IL-6 signaling amplification loop in type 1 collagen+ cells that is triggered by CD4+ T cell-derived cytokine(s) such as IL-17A, which leads to the synergistic activation of STAT3 and NFκB in non-hematopoietic cells in the joint (Murakami et al., 2011). We named this loop the IL-6-mediated inflammation amplifier, or IL-6 amplifier for

  10. Immunsystemet ved kronisk inflammation

    DEFF Research Database (Denmark)

    Bendtzen, Klaus

    2008-01-01

    Innate and adaptive immunity has evolved as a defence against infections and as an important repair mechanism after physical injury. If elimination of microbes and healing is not achieved, or if the immune system is dysregulated, chronic inflammation ensues. Immune cells become engaged in prolonged...

  11. Escin attenuates behavioral impairments, oxidative stress and inflammation in a chronic MPTP/probenecid mouse model of Parkinson's disease.

    Science.gov (United States)

    Selvakumar, Govindasamy Pushpavathi; Janakiraman, Udaiyappan; Essa, Musthafa Mohamed; Justin Thenmozhi, Arokiasamy; Manivasagam, Thamilarasan

    2014-10-17

    Parkinson's disease (PD) is a progressive neurodegenerative disorder that results mainly due to the death of dopaminergic neurons in the substantia nigra (SN), and subsequently has an effect on one's motor function and coordination. The current investigation explored the neuroprotective potential of escin, a natural triterpene-saponin on chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid (MPTP/p) induced mouse model of PD. Administration of MPTP led to the depleted striatal dopamine content, impaired patterns of behavior, enhanced oxidative stress and diminished expression of tyrosine hydroxylase (TH), dopamine transporter (DAT) and vesicular monoamine transporter-2 (VMAT-2). The expressions of interleukin-6 and -10, glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor protein-1 (IBA-1), tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS) in SN were also enhanced. Oral treatment of escin significantly attenuated MPTP/p induced dopaminergic markers depletion, physiological abnormalities, oxidative stress and inhibit neuroinflammatory cytokine expressions in SN. The result of our study confirmed that escin mediated its protection against experimental PD through its antioxidant and anti-inflammatory properties. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Chronic depletion of gonadal testosterone leads to blood-brain barrier dysfunction and inflammation in male mice.

    Science.gov (United States)

    Atallah, Afnan; Mhaouty-Kodja, Sakina; Grange-Messent, Valérie

    2017-09-01

    A dysfunction in the blood-brain barrier (BBB) is associated with many neurological and metabolic disorders. Although sex steroid hormones have been shown to impact vascular tone, endothelial function, oxidative stress, and inflammatory responses, there are still no data on the role of testosterone in the regulation of BBB structure and function. In this context, we investigated the effects of gonadal testosterone depletion on the integrity of capillary BBB and the surrounding parenchyma in male mice. Our results show increased BBB permeability for different tracers and endogenous immunoglobulins in chronically testosterone-depleted male mice. These results were associated with disorganization of tight junction structures shown by electron tomography and a lower amount of tight junction proteins such as claudin-5 and ZO-1. BBB leakage was also accompanied by activation of astrocytes and microglia, and up-regulation of inflammatory molecules such as inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), interleukin 1 beta (IL-1β), and tumor necrosis factor (TNF). Supplementation of castrated male mice with testosterone restored BBB selective permeability, tight junction integrity, and almost completely abrogated the inflammatory features. The present demonstration that testosterone transiently impacts cerebrovascular physiology in adult male mice should help gain new insights into neurological and metabolic diseases linked to hypogonadism in men of all ages.

  13. DNA-damage response associated with occupational exposure, age and chronic inflammation in workers in the automotive industry.

    Science.gov (United States)

    Savina, Natalya V; Smal, Marharyta P; Kuzhir, Tatyana D; Ershova-Pavlova, Alla A; Goncharova, Roza I

    2012-10-09

    The evaluation of genome integrity in populations occupationally exposed to combine industrial factors is of medical importance. In the present study, the DNA-damage response was estimated by means of the alkaline comet assay in a sizeable cohort of volunteers recruited among workers in the automotive industry. For this purpose, freshly collected lymphocytes were treated with hydrogen peroxide (100μM, 1min, 4°C) in vitro, and the levels of basal and H(2)O(2)-induced DNA damage, and the kinetics and efficiency of DNA repair were measured during a 180-min interval after exposure. The parameters studied in the total cohort of workers were in a range of values prescribed for healthy adult residents of Belarus. Based on the 95th percentiles, individuals possessing enhanced cellular sensitivity to DNA damage were present in different groups, but the frequency was significantly higher among elderly persons and among individuals with chronic inflammatory diseases. The results indicate that the inter-individual variations in DNA-damage response should be taken into account to estimate adequately the environmental genotoxic effects and to identify individuals with an enhanced DNA-damage response due to the influence of some external factors or intrinsic properties of the organism. Underling mechanisms need to be further explored. © 2012 Elsevier B.V. All rights reserved.

  14. Low-Level Laser Therapy Reduces Lung Inflammation in an Experimental Model of Chronic Obstructive Pulmonary Disease Involving P2X7 Receptor

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    Gabriel da Cunha Moraes

    2018-01-01

    Full Text Available Chronic obstructive pulmonary disease (COPD is a progressive disease characterized by irreversible airflow limitation, airway inflammation and remodeling, and enlargement of alveolar spaces. COPD is in the top five leading causes of deaths worldwide and presents a high economic cost. However, there are some preventive measures to lower the risk of developing COPD. Low-level laser therapy (LLLT is a new effective therapy, with very low cost and no side effects. So, our objective was to investigate if LLLT reduces pulmonary alterations in an experimental model of COPD. C57BL/6 mice were submitted to cigarette smoke for 75 days (2x/day. After 60 days to smoke exposure, the treated group was submitted to LLLT (diode laser, 660 nm, 30 mW, and 3 J/cm2 for 15 days and euthanized for morphologic and functional analysis of the lungs. Our results showed that LLLT significantly reduced the number of inflammatory cells and the proinflammatory cytokine secretion such as IL-1β, IL-6, and TNF-α in bronchoalveolar lavage fluid (BALF. We also observed that LLLT decreased collagen deposition as well as the expression of purinergic P2X7 receptor. On the other hand, LLLT increased the IL-10 release. Thus, LLLT can be pointed as a promising therapeutic approach for lung inflammatory diseases as COPD.

  15. Associations of epicardial fat with coronary calcification, insulin resistance, inflammation, and fibroblast growth factor-23 in stage 3-5 chronic kidney disease

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    Kerr Jasmine D

    2013-01-01

    Full Text Available Abstract Background Epicardial fat, quantified in a single multi-slice computed tomography (MSCT slice, is a reliable estimate of total epicardial fat volume (EFV. We sought to determine risk factors for EFV detected in a single-slice MSCT measurement (ssEFV in pre-dialysis chronic kidney disease (CKD patients. Our primary objective was to determine the association between ssEFV and coronary artery calcification (CAC. Methods 94 pre-dialysis stage 3–5 CKD patients underwent MSCT to measure ssEFV and CAC. ssEFV was quantified at the level of the left main coronary artery. Measures of inflammation, traditional and kidney-related cardiovascular disease risk factors were collected. Results Mean age: 63.7 ± 14 years, 56% male, 39% had diabetes, and mean eGFR: 25.1 ± 11.9 mL/min/1.73 m2. Mean ssEFV was 5.03 ± 2.4 cm3. By univariate analysis, body mass index (BMI (r = 0.53; P = r = 0.51; P r = − 0.39; P =  Conclusions In stage 3–5 CKD, coronary calcification and IL-6 and were predictors of ssEFV. Further studies are needed to clarify the mechanism by which epicardial fat may contribute to the pathogenesis of coronary disease, particularly in the CKD population.

  16. Myocardial123I-mIBG scintigraphy in relation to markers of inflammation and long-term clinical outcome in patients with stable chronic heart failure.

    Science.gov (United States)

    Verschure, Derk O; Lutter, René; van Eck-Smit, Berthe L F; Somsen, G Aernout; Verberne, Hein J

    2016-11-17

    Chronic heart failure (CHF) results in both increased cardiac sympathetic activity and myocardial inflammation. The aim of this study was to identify the relationship between severity of heart failure (i.e., NT-proBNP and LVEF), cardiac sympathetic activity ( 123 I-mIBG scintigraphy), and measures of inflammation in subjects with stable, optimally treated CHF. In addition, the predictive value for cardiac events (i.e., ventricular arrhythmia, progression of CHF and cardiac death) of 123 I-mIBG parameters and these inflammatory markers was evaluated. Fifty-five CHF patients (age 66.3 ± 8.0 years, 78% male, LVEF 22.4 ± 6.3) referred for cardiac 123 I-mIBG imaging were included. At 15 minutes (early) and 4 hours (late) after i.v. administration of 123 I-mIBG (185 MBq), planar images were acquired. Early Heart/Mediastinum (H/M) ratio, late H/M ratio, and 123 I-mIBG washout (WO) were calculated. NT-proBNP and markers of inflammation (i.e., C-reactive protein (CRP), IL-1β, IL-6, IL-8, IL-10, IL-12p40, tumor necrosis factor-α (TNF-α), soluble (s)E-selectin, myeloperoxidase (MPO), plasminogen activator inhibitor-1 (PAI-1), tPA, tumor necrosis factor receptor (TNFR) 1 and 2, and interferon (IFN) α and β) were measured in blood plasma samples, taken just before 123 I-mIBG administration. Mean early H/M ratio was 2.12 ± 0.39, late H/M ratio was 1.84 ± 0.40, and 123 I-mIBG WO was 13.0 ± 10.9. LVEF was the only independent predictor of late H/M ratio (adjusted R 2 = 0.100, p = 0.011). NT-proBNP was an independent predictor of 123 I-mIBG WO (adjusted R 2 = 0.090, p = 0.015). CRP, IL12p40, TNF-α, sE-selectin, MPO, PAI-1, tPA, and TNFR2 were not related to late H/M ratio and 123 I-mIBG WO. During a median follow-up of 34 months (2-58 months), 13 patients experienced a cardiac event [ventricular arrhythmia (4), progression of CHF (4), and cardiac death (5)]. Univariate Cox regression analysis showed that the risk of a cardiac event was associated with CRP (HR 1

  17. Altered Peripheral Blood Monocyte Phenotype and Function in Chronic Liver Disease: Implications for Hepatic Recruitment and Systemic Inflammation.

    Directory of Open Access Journals (Sweden)

    Victoria L Gadd

    Full Text Available Liver and systemic inflammatory factors influence monocyte phenotype and function, which has implications for hepatic recruitment and subsequent inflammatory and fibrogenic responses, as well as host defence.Peripheral blood monocyte surface marker (CD14, CD16, CD163, CSF1R, CCR2, CCR4, CCR5, CXCR3, CXCR4, CX3CR1, HLA-DR, CD62L, SIGLEC-1 expression and capacity for phagocytosis, oxidative burst and LPS-stimulated TNF production were assessed in patients with hepatitis C (HCV (n = 39 or non-alcoholic fatty liver disease (NAFLD (n = 34 (classified as non-advanced disease, compensated cirrhosis and decompensated cirrhosis and healthy controls (n = 11 by flow cytometry.The selected markers exhibited similar monocyte-subset-specific expression patterns between patients and controls. Monocyte phenotypic signatures differed between NAFLD and HCV patients, with an increased proportion of CD16+ non-classical monocytes in NAFLD, but increased expression of CXCR3 and CXCR4 in HCV. In both cohorts, monocyte CCR2 expression was reduced and CCR4 elevated over controls. CD62L expression was specifically elevated in patients with decompensated cirrhosis and positively correlated with the model-for-end-stage-liver-disease score. Functionally, monocytes from patients with decompensated cirrhosis had equal phagocytic capacity, but displayed features of dysfunction, characterised by lower HLA-DR expression and blunted oxidative responses. Lower monocyte TNF production in response to LPS stimulation correlated with time to death in 7 (46% of the decompensated patients who died within 8 months of recruitment.Chronic HCV and NAFLD differentially affect circulating monocyte phenotype, suggesting specific injury-induced signals may contribute to hepatic monocyte recruitment and systemic activation state. Monocyte function, however, was similarly impaired in patients with both HCV and NAFLD, particularly in advanced disease, which likely contributes to the increased

  18. Chronic sustained inflammation links to left ventricular hypertrophy and aortic valve sclerosis: a new link between S100/RAGE and FGF23.

    Science.gov (United States)

    Yan, Ling; Bowman, Marion A Hofmann

    dysfunction in hBAC-S100 mice with CKD. We suggest that S100/RAGE-mediated chronic sustained systemic inflammation is linked to pathological cardiac remodeling via direct up regulation of FGF23 in cardiac fibroblasts, thereby providing a new mechanistic understanding for the common association between CKD, diabetes, metabolic syndrome, or hypertension with left ventricular hypertrophy with diastolic dysfunction.

  19. Role of Inflammation in Diabetic Retinopathy

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    Anne Rübsam

    2018-03-01

    Full Text Available Diabetic retinopathy is a common complication of diabetes and remains the leading cause of blindness among the working-age population. For decades, diabetic retinopathy was considered only a microvascular complication, but the retinal microvasculature is intimately associated with and governed by neurons and glia, which are affected even prior to clinically detectable vascular lesions. While progress has been made to improve the vascular alterations, there is still no treatment to counteract the early neuro-glial perturbations in diabetic retinopathy. Diabetes is a complex metabolic disorder, characterized by chronic hyperglycemia along with dyslipidemia, hypoinsulinemia and hypertension. Increasing evidence points to inflammation as one key player in diabetes-associated retinal perturbations, however, the exact underlying molecular mechanisms are not yet fully understood. Interlinked molecular pathways, such as oxidative stress, formation of advanced glycation end-products and increased expression of vascular endothelial growth factor have received a lot of attention as they all contribute to the inflammatory response. In the current review, we focus on the involvement of inflammation in the pathophysiology of diabetic retinopathy with special emphasis on the functional relationships between glial cells and neurons. Finally, we summarize recent advances using novel targets to inhibit inflammation in diabetic retinopathy.

  20. Effects of Bone Marrow Multipotent Mesenchymal Stromal Cells and Their Secretory Products on Microcirculation in the Broad Ligament of the Uterus of Wistar Rats during Experimental Chronic Genital Inflammation.

    Science.gov (United States)

    Konenkov, V I; Borodin, Yu I; Dergacheva, T I; Shurlygina, A V; Tenditnik, M V; Starkova, E V; Poveshchenko, O V; Lykov, A P

    2017-05-01

    Effects of bone marrow multipotent mesenchymal stromal cells and their secretory products released into the conditioned medium on microcirculatory bed in the broad ligament of the uterus were studied in Wistar rats with chronic genital inflammation. Opposite changes in the parameters of microcirculation and lymphatic drainage in the broad ligament of the uterus were observed after administration of cells and conditioned medium via different routes, which should be taken into account during the treatment of inflammatory and degenerative processes in the pelvic organs.

  1. Sinonasal inflammation in COPD

    DEFF Research Database (Denmark)

    Håkansson, Kåre; Konge, Lars; Thomsen, Sf

    2013-01-01

    In this review we demonstrate that patients with chronic obstructive pulmonary disease (COPD) frequently report sinonasal symptoms. Furthermore, we present evidence that smoking on its own can cause nasal disease, and that in COPD patients, nasal inflammation mimics that of the bronchi. All...... this evidence suggests that COPD related sinonasal disease does exist and that smoking on its own rather than systemic inflammation triggers the condition. However, COPD related sinonasal disease remains to be characterized in terms of symptoms and endoscopic findings. In addition, more studies are needed...... to quantify the negative impact of sinonasal symptoms on the quality of life in COPD patients....

  2. Inflammation in Parkinson’s disease: Role of glucocorticoids

    Directory of Open Access Journals (Sweden)

    Maria Trinidad eHerrero

    2015-04-01

    Full Text Available Chronic inflammation is a major characteristic feature of Parkinson’s disease (PD. Studies in PDpatients show evidence of augmented levels of potent pro-inflammatory molecules e.g. TNF-α, iNOS,IL-1β whereas in experimental Parkinsonism it has been consistently demonstrated that dopaminergicneurons are particularly vulnerable to activated glia releasing these toxic factors. Recent geneticstudies point to the role of immune system in the etiology of PD, thus in combination withenvironmental factors, both peripheral and CNS-mediated immune responses could play importantroles in onset and progression of PD. Whereas microglia, astrocytes and infiltrating T cells are knownto mediate chronic inflammation, the roles of other immune-competent cells are less well understood.Inflammation is a tightly controlled process. One major effector system of regulation is HPA axis.Glucocorticoids released from adrenal glands upon stimulation of HPA axis, in response to either cellinjury or presence of pathogen, activate their receptor, GR. GR regulates inflammation both throughdirect transcriptional action on target genes and by indirectly inhibiting transcriptional activities oftranscriptional factors such as NF-kB, AP-1 or interferon regulatory factors. In PD patients, the HPAaxis is unbalanced and the cortisol levels are significantly increased, implying a deregulation of GRfunction in immune cells. In experimental Parkinsonism, the activation of microglial GR has a crucialeffect in diminishing microglial cell activation and reducing dopaminergic degeneration. Moreover,glucocorticoids are also known to regulate human brain vasculature as well as blood brain barrierpermeability, any dysfunction in their actions may influence infiltration of cytotoxic moleculesresulting in increased vulnerability of dopamine neurons in PD. Overall, deregulation ofGR actions is likely important in dopamine neuron degeneration throughestablishment of chronic inflammation.

  3. [Effect of WS070117M1 on chronic obstructive pulmonary disease in mice and the underling mechanisms of anti-inflammation].

    Science.gov (United States)

    Cao, Shu-hua; Xuan, Ling-ling; Wang, Dong-mei; Xie, Jian-lin; Jiang, Ren-tao; Bai, Jin-ye; Wu, Song; Hou, Qi

    2015-08-01

    The aim of this study is to investigate the anti-inflammatory effect of the adenosine derivative N6-(3-hydroxylaniline) adenosine (WS070117M1) on cigarette smoke plus LPS (lipopolysaccharide)-induced chronic obstructive pulmonary disease (COPD) in mice and its mechanism. COPD model was established by exposing male BALB/c mice to cigarette smoke and challenged with LPS inhalation. Supernatants of bronchoalveolar lavage fluid (BALF) were harvested and IL-1β, IL-6, IL-8 and TGF-β1 levels were measured by ELISA (enzyme-linked immunesorbent assay). The number of total white blood cells and neutrophils in bronchoalveolar lavage fluid was counted separately. Lung tissue was stained with Mayer 's hematoxylin and eosin for histopathologic examination. pAMPKa protein expression and distribution of lung tissue were analyzed by immunohistochemistry method. In vitro, levels of AMPKα phosphorylation in phorbol-12- myristate-13-acetate (PMA) differentiated THP-1 cells was detected by immunohistochemistry, IL-8 level in supernatants of cigarette smoke condensate stimulating PMA differentiated THP-1 cells was measured by ELISA. The results showed that WS070117M1 treatment significantly activated AMPKa in the lung tissue. It also resulted in down regulation of IL-1β, IL-6, IL-8 and TGF-β1 levels in bronchoalveolar lavage fluid and IL-8 level in cigarette smoke condensate stimulating PMA differentiated THP-1 cells. In addition, WS070117M1 could inhibit the recruitment of total white blood cells and neutrophils. These results suggest that WS070117M1 may alleviate the airway inflammation by activating AMPK in the lung tissue.

  4. High prevalence of malnutrition and inflammation in undialyzed patients with chronic renal failure in developing countries: a single center experience from eastern India.

    Science.gov (United States)

    Prakash, Jai; Raja, R; Mishra, R N; Vohra, Rubina; Sharma, Naveen; Wani, I A; Parekh, A

    2007-01-01

    Malnutrition is common in patients with chronic renal failure (CRF), and its prevalence before the initiation of dialysis is poorly characterized in these patients in developing countries. There is a paucity of data on the quantification of malnutrition and inflammation in undialyzed patients of CRF from India. This study analyzed the prevalence and causes of malnutrition in patients with CRF before the initiation of dialysis treatment. In the present study, assessments of nutritional and inflammatory status were carried out in patients with CRF. Serum albumin, body mass index (BMI), triceps skin fold thickness (TST), mid-arm muscle circumference (MAMC), and subjective global assessment (SGA) scoring were used for assessment of nutritional parameters. Serum C-reactive protein and serum ferritin level were used to assess the inflammatory state of the patient. Two hundred and three (146 male, 57 female) patients with CRF were included in the study from August 2004 to April 2006. Overall, the prevalence of malnutrition was 65% (131/203). The age of malnourished patients (93 male, 38 female) ranged from 11-82, with mean age of 52 +/- 12.68 years. The mean serum total protein and albumin were also significantly lower in patients with malnutrition in comparison to non malnourished cases (5.50 +/- 0.40 gm/dL vs. 5.74 +/- 0.38 gm/dL; p malnutrition was common in patients with CRF before the commencement of dialysis. These data indicate that an emphasis should be placed on the assessment and prevention or correction of malnutrition in patients with CRF because of its documented adverse effect on the outcome on maintenance dialysis.

  5. The Association of Ankle Brachial Index, Protein-Energy Wasting, and Inflammation Status with Cardiovascular Mortality in Patients on Chronic Hemodialysis

    Directory of Open Access Journals (Sweden)

    Hideki Ishii

    2017-04-01

    Full Text Available Protein-energy wasting (PEW is highly prevalent in hemodialysis (HD patients. We investigated the association of abnormal ankle brachial index (ABI, PEW, and chronic inflammation status with clinical prognosis in HD patients. A total of 973 HD patients were enrolled and were followed-up for 8 years. As a marker of the PEW, geriatric nutritional risk index (GNRI was used. Cut-off levels were 91.2 for GNRI defined from previous studies and 1.9 mg/L for C-reactive protein (CRP as median value, respectively. Abnormal ABI was seen in 332 (34.1% patients. Declined GNRI and elevated CRP levels were independently associated with abnormal ABI (odds ratio (OR 0.97, 95% confidence interval (CI 0.96–0.99, p = 0.0009 and OR 1.40, 95% CI 1.07–1.83, p = 0.013, respectively. GNRI levels were also independently correlated with CRP levels (β = −0.126, p < 0.0001. During follow-up period, 283 (29.1% patients died, including 123 (12.6% due to cardiovascular disease (CVD. Abnormal ABI (adjusted hazard ratio (HR 1.62, 95% CI 1.13–2.32, p = 0.0096, GNRI < 91.2 (adjusted HR 1.57, 95% CI 1.06–2.33, p = 0.023 and CRP > 1.9 mg/L (adjusted HR 1.89, 95% CI 1.31–2.77, p = 0.0007 independently predicted mortality due to CVD, respectively. In conclusion, abnormal ABI, GNRI, and CRP levels were closely associated with each other, and the combination of these variables increase their predictive values for the risk of mortality due to CVD and all-cause mortality in HD patients.

  6. Kallikrein 5-Mediated Inflammation in Rosacea

    Science.gov (United States)

    Two, Aimee M.

    2014-01-01

    Rosacea is a chronic inflammatory condition of facial skin estimated to affect more than 16 million Americans. Although the pathogenesis of rosacea is not fully understood, recent evidence in vitro as well as in vivo has supported the role of increased levels of the trypsin-like serine protease, kallikrein 5, in initiating an augmented inflammatory response in rosacea. The increase in the quantity and magnitude of biological activity of kallikrein 5 leads to production of greater quantities of cathelicidin (LL-37), an antimicrobial peptide associated with increases in innate cutaneous inflammation, vasodilation, and vascular proliferation, all of which are characteristic features of rosacea. In this article, the authors review the literature supporting the role of kallikrein 5 in the pathophysiology of rosacea, including how therapeutic interventions modulate the effects of kallikrein 5, thus providing further support for this pathophysiological model that at least partially explains many of the clinical features of cutaneous rosacea. PMID:24563692

  7. Persisting Inflammation and Chronic Immune Activation but Intact Cognitive Function in HIV-Infected Patients After Long-Term Treatment With Combination Antiretroviral Therapy

    DEFF Research Database (Denmark)

    Pedersen, Karin K; Pedersen, Maria; Gaardbo, Julie C

    2013-01-01

    Impaired cognitive function in HIV-infected patients has been suggested. Treatment with combination antiretroviral therapy (cART) restores CD4⁺ cell counts and suppresses viral replication, but immune activation and inflammation may persist. The aim of the study was to examine if cognitive function...... in HIV-infected patients was related to immune activation and inflammation....

  8. Chronic inflammation and cardiovascular risk

    African Journals Online (AJOL)

    process linking cardiovascular risk factors for atherosclerosis and its complications to an altered arterial ... others are also associated with enhanced atherosclerosis. There are many reports of the relationship ... scale prospective cohort studies have shown that CRP predicts incident myocardial infarction, stroke and ...

  9. Midkine in Inflammation

    Directory of Open Access Journals (Sweden)

    Ludwig T. Weckbach

    2011-01-01

    Full Text Available The 13 kDa heparin-binding growth factor midkine (MK was originally identified as a molecule involved in the orchestration of embryonic development. Recent studies provided evidence for a new role of MK in acute and chronic inflammatory processes. Accordingly, several inflammatory diseases including nephritis, arthritis, atherosclerosis, colitis, and autoimmune encephalitis have been shown to be alleviated in the absence of MK in animal models. Reduced leukocyte recruitment to the sites of inflammation was found to be one important mechanism attenuating chronic inflammation when MK was absent. Furthermore, MK was found to modulate expression of proinflammatory cytokines and the expansion of regulatory T-cells. Here, we review the current understanding of the role of MK in different inflammatory disorders and summarize the knowledge of MK biology.

  10. Short-term exposure to high ambient air pollution increases airway inflammation and respiratory symptoms in chronic obstructive pulmonary disease patients in Beijing, China.

    Science.gov (United States)

    Wu, Shaowei; Ni, Yang; Li, Hongyu; Pan, Lu; Yang, Di; Baccarelli, Andrea A; Deng, Furong; Chen, Yahong; Shima, Masayuki; Guo, Xinbiao

    2016-09-01

    Few studies have investigated the short-term respiratory effects of ambient air pollution in chronic obstructive pulmonary disease (COPD) patients in the context of high pollution levels in Asian cities. A panel of 23 stable COPD patients was repeatedly measured for biomarkers of airway inflammation including exhaled nitric oxide (FeNO) and exhaled hydrogen sulfide (FeH2S) (215 measurements) and recorded for daily respiratory symptoms (794person-days) in two study periods in Beijing, China in January-September 2014. Daily ambient air pollution data were obtained from nearby central air-monitoring stations. Mixed-effects models were used to estimate the associations between exposures and health measurements with adjustment for potential confounders including temperature and relative humidity. Increasing levels of air pollutants were associated with significant increases in both FeNO and FeH2S. Interquartile range (IQR) increases in PM2.5 (76.5μg/m(3), 5-day), PM10 (75.0μg/m(3), 5-day) and SO2 (45.7μg/m(3), 6-day) were associated with maximum increases in FeNO of 13.6% (95% CI: 4.8%, 23.2%), 9.2% (95% CI: 2.1%, 16.8%) and 34.2% (95% CI: 17.3%, 53.4%), respectively; and the same IQR increases in PM2.5 (6-day), PM10 (6-day) and SO2 (7-day) were associated with maximum increases in FeH2S of 11.4% (95% CI: 4.6%, 18.6%), 7.8% (95% CI: 2.3%, 13.7%) and 18.1% (95% CI: 5.5%, 32.2%), respectively. Increasing levels of air pollutants were also associated with increased odds ratios of sore throat, cough, sputum, wheeze and dyspnea. FeH2S may serve as a novel biomarker to detect adverse respiratory effects of air pollution. Our results provide potential important public health implications that ambient air pollution may pose risk to respiratory health in the context of high pollution levels in densely-populated cities in the developing world. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Inflammation-related cancer or cancer-related inflammation

    OpenAIRE

    T.G, Shrihari

    2018-01-01

    Inflammationis the body’s defensive action against various stimuli such as physical orchemical or infectious agents. Acute inflammation and their mediators help intissue repair and healing. If the inflammation aggravates chronically,non-resolved, dysregulated immune system, results release of various inflammatorymediators such as free radicals (ROS and RNS), cytokines, chemokines, growthfactors and proteolytic enzymes produced by innate and adaptive immune cellsactivate transcriptional factor...

  12. Allergic Respiratory Inflammation and Remodeling

    OpenAIRE

    Amin, Kawa

    2015-01-01

    Asthma and rhinitis are inflammatory diseases of the respiratory tract. Respiratory inflammation of the adaptive and innate immune system is the focus of this review, and chronic inflammation is not limited to the respiratory tissue. The inflammatory response, which consists of phagocytes, eosinophils, mast cells, and lymphocytes, spreads along the respiratory tract, leading to tissue damage. Mast cells and eosinophils are commonly recognized for their detrimental role in allergic reactions o...

  13. Inflammation and Cancer: Two Pieces of the Same Puzzle? | Center for Cancer Research

    Science.gov (United States)

    Chronic inflammation, in Crohn’s disease for example, is a known risk factor for malignant transformation, however the role inflammation plays in cancer initiation is poorly understood. STAT2, an important protein that regulates gene activation, is known to be stimulated by immune factors that inhibit cell growth. STAT2 also has reduced expression in the immune cells of patients with Crohn’s disease, which suggested to Ana Gamero, Ph.D., a former NCI Scholar of the Laboratory of Experimental Immunology, CCR, and now Assistant Professor at Temple University in collaboration with Nancy Colburn, Ph.D. of the Laboratory of Cancer Prevention and her colleagues, that STAT2 may be a key protein in regulating inflammation-induced cancer progression. The results of their studies were recently published in a Cancer Prevention Research article.

  14. A platelet-activating factor (PAF) receptor deficiency exacerbates diet-induced obesity but PAF/PAF receptor signaling does not contribute to the development of obesity-induced chronic inflammation.

    Science.gov (United States)

    Yamaguchi, Masahiko; Matsui, Masakazu; Higa, Ryoko; Yamazaki, Yasuhiro; Ikari, Akira; Miyake, Masaki; Miwa, Masao; Ishii, Satoshi; Sugatani, Junko; Shimizu, Takao

    2015-02-15

    Platelet-activating factor (PAF) is a well-known phospholipid that mediates acute inflammatory responses. In the present study, we investigated whether PAF/PAF receptor signaling contributed to chronic inflammation in the white adipose tissue (WAT) of PAF receptor-knockout (PAFR-KO) mice. Body and epididymal WAT weights were higher in PAFR-KO mice fed a high-fat diet (HFD) than in wild-type (WT) mice. TNF-α mRNA expression levels in epididymal WAT and the infiltration of CD11c-positive macrophages into epididymal WAT, which led to chronic inflammation, were also elevated in HFD-fed PAFR-KO mice. HFD-fed PAFR-KO mice had higher levels of fasting serum glucose than HFD-fed WT mice as well as impaired glucose tolerance. Although PAF receptor signaling up-regulated the expression of TNF-α and lipopolysaccharide induced the expression of acyl-CoA:lysophosphatidylcholine acyltransferase 2 (LPCAT2) mRNA in bone marrow-derived macrophages, no significant differences were observed in the expression of LPCAT2 mRNA and PAF levels in epididymal WAT between HFD-fed mice and normal diet-fed mice. In addition to our previous finding in which energy expenditure in PAF receptor (PAFR)-deficient mice was low due to impaired brown adipose tissue function, the present study demonstrated that PAF/PAF receptor signaling up-regulated the expression of Ucp1 mRNA, which is essential for cellular thermogenesis, in 3T3-L1 adipocytes. We concluded that the marked accumulation of abdominal fat due to HFD feeding led to more severe chronic inflammation in WAT, which is associated with glucose metabolism disorders, in PAFR-KO mice than in WT mice, and PAF/PAF receptor signaling may regulate energy expenditure and adiposity. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. inflammation and iron metabolism

    Directory of Open Access Journals (Sweden)

    A Dzedzej

    2016-08-01

    Full Text Available Following acute physical activity, blood hepcidin concentration appears to increase in response to exercise-induced inflammation, but the long-term impact of exercise on hepcidin remains unclear. Here we investigated changes in hepcidin and the inflammation marker interleukin-6 to evaluate professional basketball players’ response to a season of training and games. The analysis also included vitamin D (25(OHD3 assessment, owing to its anti-inflammatory effects. Blood samples were collected for 14 players and 10 control non-athletes prior to and after the 8-month competitive season. Athletes’ performance was assessed with the NBA efficiency score. At the baseline hepcidin correlated with blood ferritin (r=0.61; 90% CL ±0.31, but at the end of the season this correlation was absent. Compared with the control subjects, athletes experienced clear large increases in hepcidin (50%; 90% CI 15-96% and interleukin-6 (77%; 90% CI 35-131% and a clear small decrease in vitamin D (-12%; 90% CI -20 to -3% at the season completion. Correlations between change scores of these variables were unclear (r = -0.21 to 0.24, 90% CL ±0.5, but their uncertainty generally excluded strong relationships. Athletes were hence concluded to have experienced acute inflammation at the beginning but chronic inflammation at the end of the competitive season. At the same time, the moderate correlation between changes in vitamin D and players’ performance (r=0.43 was suggestive of its beneficial influence. Maintaining the appropriative concentration of vitamin D is thus necessary for basketball players’ performance and efficiency. The assessment of hepcidin has proven to be useful in diagnosing inflammation in response to chronic exercise.

  16. Nutrition, inflammation, and cognitive function.

    Science.gov (United States)

    Wärnberg, Julia; Gomez-Martinez, Sonia; Romeo, Javier; Díaz, Ligia-Esperanza; Marcos, Ascensión

    2009-02-01

    Inflammation, particularly low-grade chronic inflammation, appears to affect several brain functions, from early brain development to the development of neurodegenerative disorders and perhaps some psychiatric diseases. On the other hand, nutrition and dietary components and patterns have a plethora of anti- and pro-inflammatory effects that could be linked to cognitive function. Even a modest effect of nutrition on cognitive decline could have significant implications for public health. This paper summarizes the available evidence regarding inflammation as a key mechanism in cognitive function and nutritional pro- or anti-inflammatory effects with the purpose of linking the apparent disparate disciplines of nutrition, immunity, and neurology.

  17. Peritoneal dialysis and inflammation.

    Science.gov (United States)

    Velloso, Marina Souza Silva; Otoni, Alba; de Paula Sabino, Adriano; de Castro, Whocely Victor; Pinto, Sérgio Wyton Lima; Marinho, Maria Aparecida Silva; Rios, Danyelle Romana Alves

    2014-03-20

    Peritoneal dialysis (PD) is a kidney replacement therapy for end stage renal disease (ESRD) patients. Despite being a lifesaving treatment, the rate of mortality in patients under PD is elevated, mainly due to the chronic peritoneal dysfunction which is characterized by inflammation, peritoneal fibrosis and neoangiogenesis. The inflammatory process is trigged and modulated by the type of the peritoneal dialysis solutions (PDSs) used during PD. Currently, different PDSs are commercially available: (i) the conventional solutions; (ii) solutions of neutral pH containing low concentration of glucose degradation products (GDPs); (iii) solutions with icodextrin; and (iv) solutions containing taurine. Therefore, the aim of this review is to describe the different types of peritoneal dialysis solutions used during PD and their relationship with systemic and intraperitoneal inflammation. Some studies suggested that solutions of neutral pH containing low concentration of GDPs, icodextrin and taurine have better biocompatibility and lower influence on the inflammatory process compared to the conventional one. On the other hand, the studies, in general, were performed with a small population and for a short period of time. Therefore, further well-designed and -controlled clinical trials with larger number of individuals are required in order to better understand the role of different peritoneal dialysis solution types in the development of inflammation in patients with chronic peritoneal dialysis. Accordingly, studies that are more well-designed, well-controlled and with a larger number of patients are needed to explain and define the role of different types of PDS in the inflammation development in patients with chronic peritoneal dialysis. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Bioactive Egg Components and Inflammation

    Directory of Open Access Journals (Sweden)

    Catherine J. Andersen

    2015-09-01

    Full Text Available Inflammation is a normal acute response of the immune system to pathogens and tissue injury. However, chronic inflammation is known to play a significant role in the pathophysiology of numerous chronic diseases, such as cardiovascular disease, type 2 diabetes mellitus, and cancer. Thus, the impact of dietary factors on inflammation may provide key insight into mitigating chronic disease risk. Eggs are recognized as a functional food that contain a variety of bioactive compounds that can influence pro- and anti-inflammatory pathways. Interestingly, the effects of egg consumption on inflammation varies across different populations, including those that are classified as healthy, overweight, metabolic syndrome, and type 2 diabetic. The following review will discuss the pro- and anti-inflammatory properties of egg components, with a focus on egg phospholipids, cholesterol, the carotenoids lutein and zeaxanthin, and bioactive proteins. The effects of egg consumption of inflammation across human populations will additionally be presented. Together, these findings have implications for population-specific dietary recommendations and chronic disease risk.

  19. Bioactive Egg Components and Inflammation

    Science.gov (United States)

    Andersen, Catherine J.

    2015-01-01

    Inflammation is a normal acute response of the immune system to pathogens and tissue injury. However, chronic inflammation is known to play a significant role in the pathophysiology of numerous chronic diseases, such as cardiovascular disease, type 2 diabetes mellitus, and cancer. Thus, the impact of dietary factors on inflammation may provide key insight into mitigating chronic disease risk. Eggs are recognized as a functional food that contain a variety of bioactive compounds that can influence pro- and anti-inflammatory pathways. Interestingly, the effects of egg consumption on inflammation varies across different populations, including those that are classified as healthy, overweight, metabolic syndrome, and type 2 diabetic. The following review will discuss the pro- and anti-inflammatory properties of egg components, with a focus on egg phospholipids, cholesterol, the carotenoids lutein and zeaxanthin, and bioactive proteins. The effects of egg consumption of inflammation across human populations will additionally be presented. Together, these findings have implications for population-specific dietary recommendations and chronic disease risk. PMID:26389951

  20. Airways inflammation and treatment during acute exacerbations of COPD

    NARCIS (Netherlands)

    Bathoorn, Erik; Kerstjens, Huib; Postma, Dirkje; Timens, Wim; MacNee, William

    2008-01-01

    INTRODUCTION: Inflammation is a core feature of acute chronic obstructive pulmonary disease (COPD) exacerbations. It is important to focus on inflammation since it gives insight into the pathological changes causing an exacerbation, thereby possibly providing directions for future therapies which

  1. Prostate cancer and inflammation: the evidence

    Science.gov (United States)

    Sfanos, Karen S; De Marzo, Angelo M

    2014-01-01

    Chronic inflammation is now known to contribute to several forms of human cancer, with an estimated 20% of adult cancers attributable to chronic inflammatory conditions caused by infectious agents, chronic noninfectious inflammatory diseases and / or other environmental factors. Indeed, chronic inflammation is now regarded as an ‘enabling characteristic’ of human cancer. The aim of this review is to summarize the current literature on the evidence for a role for chronic inflammation in prostate cancer aetiology, with a specific focus on recent advances regarding the following: (i) potential stimuli for prostatic inflammation; (ii) prostate cancer immunobiology; (iii) inflammatory pathways and cytokines in prostate cancer risk and development; (iv) proliferative inflammatory atrophy (PIA) as a risk factor lesion to prostate cancer development; and (v) the role of nutritional or other antiinflammatory compounds in reducing prostate cancer risk. PMID:22212087

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

    LENUS (Irish Health Repository)

    Packard, Chris J

    2011-01-17

    Abstract 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, Auditory Verbal Learning Test) were likewise related to early life conditions (P < 0.001). In multivariate models inclusion of inflammatory variables reduced the impact and independence of early life conditions on lung function and measures of cognitive ability. Including variables of adult socioeconomic status attenuated the early life associations with disease biomarkers. Conclusions Adverse levels of biomarkers of ill health in adults appear to be influenced by father\\'s occupation and childhood home conditions. Chronic inflammation and endothelial activation may in part act as intermediary phenotypes in this complex relationship. Reducing the \\'health divide\\' requires that these life course determinants are taken into account.

  3. The effect and safety of highly standardized Ginger (Zingiber officinale) and Echinacea (Echinacea angustifolia) extract supplementation on inflammation and chronic pain in NSAIDs poor responders. A pilot study in subjects with knee arthrosis.

    Science.gov (United States)

    Rondanelli, Mariangela; Riva, Antonella; Morazzoni, Paolo; Allegrini, Pietro; Faliva, Milena Anna; Naso, Maurizio; Miccono, Alessandra; Peroni, Gabriella; Degli Agosti, Irene; Perna, Simone

    2017-06-01

    The study aimed to evaluate the effect of Zingiber officinale and Echinacea angustifolia extract supplementation (25 mg of ginger and 5 mg of Echinacea) for 30 days on inflammation and chronic pain in knee osteoarthritis (OA). Consecutive nonsteroidal anti-inflammatory-drugs (NSAIDs) poor responders with chronic inflammation and pain due to knee arthrosis were assessed (15 subjects, age: 67.2 ± 7.9, body mass index: 30.6 ± 7.1, men/women:2/13). The primary endpoint was to determine pain improvement from baseline to Day 30 by Tegner Lysholm Knee Scoring. The secondary endpoints were the assessment of Visual Analog Scale for Pain, health-related quality of life, by the ShortForm36 (SF-36), anthropometric parameters, hydration. After supplementation, a significant improvement of 12.27 points was observed for Lysholm scale score (p < 0.05), SF-36 (p < 0.05), and a decrease in -0.52 cm in knee circumference (left) (p < 0.01). This pilot study provides feasibility and safety data for the use of highly standardised ginger and Echinacea extract supplementation in people with knee OA.

  4. Cell adhesion molecules and hyaluronic acid as markers of inflammation, fibrosis and response to antiviral therapy in chronic hepatitis C patients

    Directory of Open Access Journals (Sweden)

    Esther Granot

    2001-01-01

    Full Text Available Objective: Cell adhesion molecules (intracellular adhesion molecule-1 (ICAM-1, vascular cell adhesion molecule-1 (VCAM-1 and hyaluronic acid, markers of inflammation and fibrosis were monitored in hepatitis C patients to determine whether changes in plasma levels, during antiviral treatment, can predict long-term response to therapy.

  5. Natural resolution of inflammation.

    Science.gov (United States)

    Freire, Marcelo O; Van Dyke, Thomas E

    2013-10-01

    (by macrophages) of apoptotic polymorphonuclear neutrophils, foreign agents (bacteria) and necrotic debris from the site. While an acute inflammatory response that is resolved in a timely manner prevents tissue injury, inadequate resolution and failure to return tissue to homeostasis results in neutrophil-mediated destruction and chronic inflammation. A better understanding of the complex mechanisms of lipid agonist mediators, cell targets and actions allows us to exploit and develop novel therapeutic strategies to treat human inflammatory diseases, including periodontal diseases. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Reparative inflammation takes charge of tissue regeneration

    NARCIS (Netherlands)

    Karin, Michael; Clevers, Hans

    2016-01-01

    Inflammation underlies many chronic and degenerative diseases, but it also mitigates infections, clears damaged cells and initiates tissue repair. Many of the mechanisms that link inflammation to damage repair and regeneration in mammals are conserved in lower organisms, indicating that it is an

  7. Immunsystemet ved kronisk inflammation

    DEFF Research Database (Denmark)

    Bendtzen, Klaus

    2008-01-01

    Innate and adaptive immunity has evolved as a defence against infections and as an important repair mechanism after physical injury. If elimination of microbes and healing is not achieved, or if the immune system is dysregulated, chronic inflammation ensues. Immune cells become engaged in prolonged...... reactions with other cell types in vessels and organs, frequently with superimposed autoreactive T-cells and autoantibody-producing B-cells/plasma cells. The processes are distinguished on the basis of clinical manifestations in organ-specific and systemic inflammatory diseases. The underlying factors...

  8. Inflammation in Achromobacter xylosoxidans infected cystic fibrosis patients

    DEFF Research Database (Denmark)

    Hansen, C. R.; Pressler, T.; Nielsen, K. G.

    2010-01-01

    BACKGROUND: Achromobacter xylosoxidans infection may cause conspicuous chronic pulmonary inflammation in cystic fibrosis (CF) patients similar to Pseudomonas aeruginosa and the Burkholderia cepacia complex (Bcc). Evolution in lung function was compared in chronically infected patients. Cytokine...

  9. Cytokines and intestinal inflammation.

    Science.gov (United States)

    Bamias, Giorgos; Cominelli, Fabio

    2016-11-01

    Cytokines of the intestinal microenvironment largely dictate immunological responses after mucosal insults and the dominance of homeostatic or proinflammatory pathways. This review presents important recent studies on the role of specific cytokines in the pathogenesis of intestinal inflammation. The particular mucosal effects of cytokines depend on their inherent properties but also the cellular origin, type of stimulatory antigens, intermolecular interactions, and the particular immunological milieu. Novel cytokines of the interleukin-1 (IL-1) family, including IL-33 and IL-36, have dominant roles in mucosal immunity, whereas more established ones such as IL-18 are constantly enriched with unique properties. Th17 cells are important mucosal constituents, although their profound plasticity, makes the specific set of cytokines they secrete more important than their mere numbers. Finally, various cytokines, such as tumor necrosis factor-α, IL-6, tumor necrosis factor-like cytokine 1A, and death receptor, 3 demonstrate dichotomous roles with mucosa-protective function in acute injury but proinflammatory effects during chronic inflammation. The role of cytokines in mucosal health and disease is increasingly revealed. Such information not only will advance our understanding of the pathogenesis of gut inflammation, but also set the background for development of reliable diagnostic and prognostic biomarkers and cytokine-specific therapies.

  10. How operating room efficiency is understood in a surgical team: a qualitative study.

    Science.gov (United States)

    Arakelian, Erebouni; Gunningberg, Lena; Larsson, Jan

    2011-02-01

    Building surgical teams is one attempt to ensure the health-care system becomes more efficient, but how is 'efficiency' understood or interpreted? The aim was to study how organized surgical team members and their leaders understood operating room efficiency. Qualitative study. A 1100-bed Swedish university hospital. Eleven participants, nine team members from the same team and their two leaders were interviewed. The analysis was performed according to phenomenography, a research approach that aims to discover variations in peoples' understanding of a phenomenon. Seven ways of understanding operating room efficiency were identified: doing one's best from one's prerequisites, enjoying work and adjusting it to the situation, interacting group performing parallel tasks, working with minimal resources to produce desired results, fast work with preserved quality, long-term effects for patient care and a relative concept. When talking about the quality and benefits of delivered care, most team members invoked the patient as the central focus. Despite seven ways of understanding efficiency between the team members, they described their team as efficien