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Sample records for chronic inflammation resembling

  1. Chronic skin inflammation accelerates macrophage cholesterol crystal formation and atherosclerosis

    Science.gov (United States)

    Ng, Qimin; Sanda, Gregory E.; Dey, Amit K.; Teague, Heather L.; Sorokin, Alexander V.; Dagur, Pradeep K.; Silverman, Joanna I.; Harrington, Charlotte L.; Rodante, Justin A.; Rose, Shawn M.; Varghese, Nevin J.; Belur, Agastya D.; Goyal, Aditya; Gelfand, Joel M.; Springer, Danielle A.; Bleck, Christopher K.E.; Thomas, Crystal L.; Yu, Zu-Xi; Winge, Mårten C.G.; Kruth, Howard S.; Marinkovich, M. Peter; Joshi, Aditya A.; Playford, Martin P.; Mehta, Nehal N.

    2018-01-01

    Inflammation is critical to atherogenesis. Psoriasis is a chronic inflammatory skin disease that accelerates atherosclerosis in humans and provides a compelling model to understand potential pathways linking these diseases. A murine model capturing the vascular and metabolic diseases in psoriasis would accelerate our understanding and provide a platform to test emerging therapies. We aimed to characterize a new murine model of skin inflammation (Rac1V12) from a cardiovascular standpoint to identify novel atherosclerotic signaling pathways modulated in chronic skin inflammation. The RacV12 psoriasis mouse resembled the human disease state, including presence of systemic inflammation, dyslipidemia, and cardiometabolic dysfunction. Psoriasis macrophages had a proatherosclerotic phenotype with increased lipid uptake and foam cell formation, and also showed a 6-fold increase in cholesterol crystal formation. We generated a triple-genetic K14-RacV12–/+/Srb1–/–/ApoER61H/H mouse and confirmed psoriasis accelerates atherogenesis (~7-fold increase). Finally, we noted a 60% reduction in superoxide dismutase 2 (SOD2) expression in human psoriasis macrophages. When SOD2 activity was restored in macrophages, their proatherogenic phenotype reversed. We demonstrate that the K14-RacV12 murine model captures the cardiometabolic dysfunction and accelerates vascular disease observed in chronic inflammation and that skin inflammation induces a proatherosclerotic macrophage phenotype with impaired SOD2 function, which associated with accelerated atherogenesis. PMID:29321372

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

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    Chen, Mei; Xu, Heping

    2016-01-01

    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 due to its unique anatomical and physiological 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, undergo low levels of activation (para-inflammation). In many cases, this para-inflammatory response can maintain homeostasis in the healthy aging eye. However, in patients with age-related macular degeneration (AMD), this para-inflammatory response becomes dysregulated and contributes to macular damage. Factors contributing to the dysregulation of age-related retinal para-inflammation include genetic predisposition, environmental risk factors and old age. Dysregulated para-inflammation (chronic inflammation) in AMD damages the blood retina barrier (BRB), 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 AMD, and explores the difference between beneficial para-inflammation and the detrimental chronic inflammation in the context of AMD. PMID:26292978

  3. 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.

  4. Polycystic ovary syndrome and chronic inflammation: pharmacotherapeutic implications.

    Science.gov (United States)

    Sirmans, Susan Maureen; Weidman-Evans, Emily; Everton, Victoria; Thompson, Daniel

    2012-03-01

    To examine the relationship between polycystic ovary syndrome (PCOS), cardiovascular risk factors, cardiovascular disease (CVD), and chronic inflammation and analyze data regarding pharmacologic therapies that are recommended to reduce CVD risk in PCOS and the impact of those therapies on chronic inflammation. A search of MEDLINE (1950-October 2011) was conducted to identify clinical studies pertaining to the identification and treatment of CVD and chronic low-grade inflammation in PCOS. Search terms included polycystic ovary syndrome, cardiovascular disease, inflammation, metformin, thiazolidinedione, and statin. Bibliographies of these studies and review articles were also examined. English-language clinical studies evaluating the effect of metformin, thiazolidinediones, and statins on inflammatory markers, endothelial function, adhesion molecules, fibrinolysis, cytokines, and adipokines in PCOS were included. Women with PCOS have an increased prevalence of many cardiovascular risk factors including obesity, android fat distribution, insulin resistance, impaired glucose tolerance, diabetes, dyslipidemia, hypertension, and metabolic syndrome. Markers of chronic low-grade inflammation, which are associated with an increased risk of CVD, are also elevated in PCOS. Clinical guidelines recommend the use of insulin sensitizers and statins to prevent CVD in some patients with PCOS. Current literature indicates that each of these medication classes has beneficial effects on inflammation, as well. Although there are currently no studies to determine whether these treatments decrease CVD in PCOS, it can be hypothesized that drugs impacting chronic inflammation may reduce cardiovascular risk. Some studies show that metformin, thiazolidinediones, and statins have beneficial effects on inflammatory markers in PCOS; however, the data are inconsistent. There is insufficient information to recommend any pharmacologic therapies for their antiinflammatory effects in PCOS in the

  5. Chronic inflammation in refractory hippocampal sclerosis-related temporal lobe epilepsy.

    Science.gov (United States)

    Gales, Jordan M; Prayson, Richard A

    2017-10-01

    Emerging evidence suggests chronic inflammation may play a role in hippocampal sclerosis-associated temporal lobe epilepsy. We sought to systematically evaluate for its presence in a group of 315 patients who underwent surgery for medically-refractory epilepsy and who had hippocampal sclerosis. Upon histologic review of hematoxylin and eosin stained tissue sections, 95 (41%) cases demonstrated the presence of lymphocytes within the perivascular region and diffusely within the brain parenchyma. Those cases with chronic inflammation evident on hematoxylin and eosin staining were significantly more likely to experience a post-operative seizure recurrence than those without it (p=0.03). In 9 cases of hippocampi with chronic inflammation observed on hematoxylin and eosin stained sections, there was a mixture of both T (CD3+) and B (CD20+) lymphocytes located around blood vessels and interspersed within the brain parenchyma and a predominance of CD4 positive T cells versus CD8 positive cells. Ten hippocampi, apparently devoid of chronic inflammation upon inspection with hematoxylin and eosin stained sections, were stained with the lymphocyte common antigen CD45. In all 10 cases, scattered lymphoid cells were observed in the brain parenchyma, suggesting some level of chronic inflammation may be present in more cases than casual inspection might suggest. This study was the first to evaluate the incidence of chronic inflammation within a large temporal lobe epilepsy population. The study findings suggest chronic inflammation may be a more common component of hippocampal sclerosis -associated temporal lobe epilepsy than previously believed. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Chronic Orbital Inflammation Associated to Hydroxyapatite Implants in Anophthalmic Sockets

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    Alicia Galindo-Ferreiro

    2017-12-01

    Full Text Available Purpose: We report 6 patients who received a hydroxyapatite (HA orbital implant in the socket and developed chronic orbital inflammation unresponsive to conventional medical therapy. Case Reports: We assisted 6 cases (4 males, 2 females who received an HA orbital implant in the socket between 2015 and 2016 at King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia, and developed chronic orbital inflammation with chronic discharge, redness, and pain (onset from weeks to over 2 decades after surgery. Computed tomography evaluation indicated inflammation in the orbital tissues, and histological examination showed a foreign body granulomatous reaction mainly localized around and blanching the HA implant. The condition was unresponsive to usual medical treatment and was resolved immediately after implant removal. Conclusions: Chronic inflammation can occur decades after placement of an HA implant in the orbit and can be successfully treated with implant removal.

  7. 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

  8. 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.

  9. 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.

  10. Decreased MORF leads to prolonged endoplasmic reticulum stress in periodontitis-associated chronic inflammation.

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    Xue, Peng; Li, Bei; An, Ying; Sun, Jin; He, Xiaoning; Hou, Rui; Dong, Guangying; Fei, Dongdong; Jin, Fang; Wang, Qintao; Jin, Yan

    2016-11-01

    The association between inflammation and endoplasmic reticulum (ER) stress has been described in many diseases. However, if and how chronic inflammation governs the unfolded protein response (UPR) and promotes ER homeostasis of chronic inflammatory disease remains elusive. In this study, chronic inflammation resulted in ER stress in mesenchymal stem cells in the setting of periodontitis. Long-term proinflammatory cytokines induced prolonged ER stress and decreased the osteogenic differentiation of periodontal ligament stem cells (PDLSCs). Interestingly, we showed that chronic inflammation decreases the expression of lysine acetyltransferase 6B (KAT6B, also called MORF), a histone acetyltransferase, and causes the upregulation of a key UPR sensor, PERK, which lead to the persistent activation of the UPR in PDLSCs. Furthermore, we found that the activation of UPR mediated by MORF in chronic inflammation contributes to the PERK-related deterioration of the osteogenic differentiation of PDLSCs both in vivo and in vitro. Taken together, our results suggest that chronic inflammation compromises UPR function through MORF-mediated-PERK transcription, which is a previously unrecognized mechanism that contributes to impaired ER function, prolonged ER stress and defective osteogenic differentiation of PDLSCs in periodontitis.

  11. [Bronchial inflammation during chronic bronchitis, importance of fenspiride].

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    Melloni, B

    2002-09-01

    PATHOPHYSIOLOGY OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD): Chronic inflammation of the upper airways, pulmonary parenchyma and pulmonary vasculature is the characteristic feature of COPD. Two mechanisms besides inflammation are also involved: oxidative stress and imbalance between proteinases and antiproteinases. Cellular infiltration of the upper airways involved neutrophils, macrophages, T lymphocytes and eosinophils. Inflammatory mediators appear to play a crucial role in the interaction between inflammation and obstruction. PROPERTIES OF FENSPIRIDE: A nonsteroidal drug, fenspiride, exhibits interesting properties documented in vitro: anti-bronchoconstriction activity, anti-secretory activity, and anti-inflammatory activity (reduction in the activity of phospholipase A2 and release of proinflammatory leukotriens). Two french clinical trials have studied the efficacy of fenspiride in patients with acute excerbation or stable COPD and have demonstrated an improvement in the group treated with fenspiride compared with the placebo group.

  12. Bioactive Lipids and Chronic Inflammation: Managing the Fire Within

    Directory of Open Access Journals (Sweden)

    Valerio Chiurchiù

    2018-01-01

    Full Text Available Inflammation is an immune response that works as a contained fire that is pre-emptively sparked as a defensive process during infections or upon any kind of tissue insult, and that is spontaneously extinguished after elimination or termination of the damage. However, persistent and uncontrolled immune reactions act as a wildfire that promote chronic inflammation, unresolved tissue damage and, eventually, chronic diseases. A wide network of soluble mediators, among which endogenous bioactive lipids, governs all immune processes. They are secreted by basically all cells involved in inflammatory processes and constitute the crucial infrastructure that triggers, coordinates and confines inflammatory mechanisms. However, these molecules are also deeply involved in the detrimental transition from acute to chronic inflammation, be it for persistent or excessive action of pro-inflammatory lipids or for the impairment of the functions carried out by resolving ones. As a matter of fact, bioactive lipids have been linked, to date, to several chronic diseases, including rheumatoid arthritis, atherosclerosis, diabetes, cancer, inflammatory bowel disease, systemic lupus erythematosus, and multiple sclerosis. This review summarizes current knowledge on the involvement of the main classes of endogenous bioactive lipids—namely classical eicosanoids, pro-resolving lipid mediators, lysoglycerophospholipids/sphingolipids, and endocannabinoids—in the cellular and molecular mechanisms that lead to the pathogenesis of chronic disorders.

  13. The role of chronic prostatic inflammation in the pathogenesis and progression of benign prostatic hyperplasia (BPH).

    Science.gov (United States)

    Gandaglia, Giorgio; Briganti, Alberto; Gontero, Paolo; Mondaini, Nicola; Novara, Giacomo; Salonia, Andrea; Sciarra, Alessandro; Montorsi, Francesco

    2013-08-01

    Several different stimuli may induce chronic prostatic inflammation, which in turn would lead to tissue damage and continuous wound healing, thus contributing to prostatic enlargement. Patients with chronic inflammation and benign prostatic hyperplasia (BPH) have been shown to have larger prostate volumes, more severe lower urinary tract symptoms (LUTS) and a higher probability of acute urinary retention than their counterparts without inflammation. Chronic inflammation could be a predictor of poor response to BPH medical treatment. Thus, the ability to identify patients with chronic inflammation would be crucial to prevent BPH progression and develop target therapies. Although the histological examination of prostatic tissue remains the only available method to diagnose chronic inflammation, different parameters, such as prostatic calcifications, prostate volume, LUTS severity, storage and prostatitis-like symptoms, poor response to medical therapies and urinary biomarkers, have been shown to be correlated with chronic inflammation. The identification of patients with BPH and chronic inflammation might be crucial in order to develop target therapies to prevent BPH progression. In this context, clinical, imaging and laboratory parameters might be used alone or in combination to identify patients that harbour chronic prostatic inflammation. © 2013 BJU International.

  14. 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)

  15. Periodontal treatment reduces chronic systemic inflammation in peritoneal dialysis patients.

    Science.gov (United States)

    Siribamrungwong, Monchai; Yothasamutr, Kasemsuk; Puangpanngam, Kutchaporn

    2014-06-01

    Chronic systemic inflammation, a non traditional risk factor of cardiovascular diseases, is associated with increasing mortality in chronic kidney disease, especially peritoneal dialysis patients. Periodontitis is a potential treatable source of systemic inflammation in peritoneal dialysis patients. Clinical periodontal status was evaluated in 32 stable chronic peritoneal dialysis patients by plaque index and periodontal disease index. Hematologic, blood chemical, nutritional, and dialysis-related data as well as highly sensitive C-reactive protein were analyzed before and after periodontal treatment. At baseline, high sensitive C-reactive protein positively correlated with the clinical periodontal status (plaque index; r = 0.57, P periodontal disease index; r = 0.56, P periodontal therapy, clinical periodontal indexes were significantly lower and high sensitivity C-reactive protein significantly decreased from 2.93 to 2.21 mg/L. Moreover, blood urea nitrogen increased from 47.33 to 51.8 mg/dL, reflecting nutritional status improvement. Erythropoietin dosage requirement decreased from 8000 to 6000 units/week while hemoglobin level was stable. Periodontitis is an important source of chronic systemic inflammation in peritoneal dialysis patients. Treatment of periodontal diseases can improve systemic inflammation, nutritional status and erythropoietin responsiveness in peritoneal dialysis patients. © 2013 The Authors. Therapeutic Apheresis and Dialysis © 2013 International Society for Apheresis.

  16. DNA methylation signatures of chronic low-grade inflammation are associated with complex diseases

    NARCIS (Netherlands)

    S. Ligthart (Symen); Marzi, C. (Carola); Aslibekyan, S. (Stella); Mendelson, M.M. (Michael M.); K.N. Conneely (Karen N.); T. Tanaka (Toshiko); Colicino, E. (Elena); L. Waite (Lindsay); R. Joehanes (Roby); W. Guan (Weihua); J. Brody (Jennifer); C.E. Elks (Cathy); R.E. Marioni (Riccardo); M.A. Jhun (Min A.); Agha, G. (Golareh); J. Bressler (Jan); C.K. Ward-Caviness (Cavin K.); B.H. Chen (Brian); T. Huan (Tianxiao); K.M. Bakulski (Kelly M.); E. Salfati (Elias); Fiorito, G. (Giovanni); S. Wahl (Simone); K. Schramm (Katharina); Sha, J. (Jin); D.G. Hernandez (Dena); Just, A.C. (Allan C.); J.A. Smith (Jennifer A); N. Sotoodehnia (Nona); L.C. Pilling (Luke); J.S. Pankow (James); Tsao, P.S. (Phil S.); Liu, C. (Chunyu); W. Zhao (Wei); S. Guarrera (Simonetta); Michopoulos, V.J. (Vasiliki J.); Smith, A.K. (Alicia K.); M.J. Peters (Marjolein); D. Melzer (David); Vokonas, P. (Pantel); M. Fornage (Myriam); H. Prokisch (Holger); J.C. Bis (Joshua); A.Y. Chu (Audrey); C. Herder (Christian); H. Grallert (Harald); C. Yao (Chen); S. Shah (Sonia); A.F. McRae (Allan F.); H. Lin; S. Horvath (Steve); Fallin, D. (Daniele); A. Hofman (Albert); N.J. Wareham (Nick); K.L. Wiggins (Kerri); A.P. Feinberg (Andrew P.); J.M. Starr (John); P.M. Visscher (Peter); J. Murabito (Joanne); Kardia, S.L.R. (Sharon L.R.); D. Absher (Devin); E.B. Binder (Elisabeth); A. Singleton (Andrew); S. Bandinelli (Stefania); A. Peters (Annette); M. Waldenberger (Melanie); G. Matullo; Schwartz, J.D. (Joel D.); E.W. Demerath (Ellen); A.G. Uitterlinden (André); Meurs, J.B.J. (Joyce B.J.); O.H. Franco (Oscar); Y.D. Chen (Y.); D. Levy (Daniel); S.T. Turner (Stephen); I.J. Deary (Ian J.); K.J. Ressler (Kerry); J. Dupuis (Josée); L. Ferrucci (Luigi); Ong, K.K. (Ken K.); T.L. Assimes (Themistocles); E.A. Boerwinkle (Eric); W. Koenig (Wolfgang); D.K. Arnett (Donna); A.A. Baccarelli (Andrea A.); E.J. Benjamin (Emelia); A. Dehghan (Abbas)

    2016-01-01

    textabstractBackground: Chronic low-grade inflammation reflects a subclinical immune response implicated in the pathogenesis of complex diseases. Identifying genetic loci where DNA methylation is associated with chronic low-grade inflammation may reveal novel pathways or therapeutic targets for

  17. 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.

  18. [Chronic mild inflammation links obesity, metabolic syndrome, atherosclerosis and diabetes].

    Science.gov (United States)

    Andel, M; Polák, J; Kraml, P; Dlouhý, P; Stich, V

    2009-01-01

    Chronic low grade inflammation is relatively new concept in metabolic medicine. This concept describes the relations between the inflammation and adipose tissue, insulin resistence, atherosclerosis and type 2 diabetes mellitus. Macrophages and lymphocytes deposed in adipose tissue produce proinflammatory cytokines which directly or through the CRP liver secretion are targeting endothelial cells, hepatocytes and beta cells of Langerhans islets of pancreas. The dysfunction of these cells follows often further disturbances and in case of beta cells - the cell death. The connection between the adipose tissue insulin resistence, atherosclerosis and type 2 diabetes was earlier described with endocrine and metabolic descriptors. The concept of chronic low grade inflammation creates also another description of multilateral connections in metabolic syndome. The salicylates and the drugs related to them seem to have some glucose lowering properties. The recent development in the field ofchronic low grade inflammation represents also certain therapeutic hope for antiinflammatory intervention in type 2 diabetes.

  19. Evolutionary medicine and bone loss in chronic inflammatory diseases--A theory of inflammation-related osteopenia.

    Science.gov (United States)

    Straub, Rainer H; Cutolo, Maurizio; Pacifici, Roberto

    2015-10-01

    Bone loss is typical in chronic inflammatory diseases such as rheumatoid arthritis, psoriasis, ankylosing spondylitis, systemic lupus erythematosus, multiple sclerosis, inflammatory bowel diseases, pemphigus vulgaris, and others. It is also typical in transplantation-related inflammation and during the process of aging. While we recognized that bone loss is tightly linked to immune system activation or inflamm-aging in the form of acute, chronic active, or chronic smoldering inflammation, bone loss is typically discussed to be an "accident of inflammation." Extensive literature search in PubMed central. Using elements of evolutionary medicine, energy regulation, and neuroendocrine regulation of homeostasis and immune function, we work out that bone waste is an adaptive, evolutionarily positively selected program that is absolutely necessary during acute inflammation. However, when acute inflammation enters a chronic state due to the inability to terminate inflammation (e.g., in autoimmunity or in continuous immunity against microbes), the acute program of bone loss is a misguided adaptive program. The article highlights the complexity of interwoven pathways of osteopenia. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Chronic Inflammation Links Cancer and Parkinson’s disease

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    Zhiming eLi

    2016-06-01

    Full Text Available An increasing number of genetic studies suggest that the pathogenesis of Parkinson’s disease (PD and cancer share common genes, pathways, and mechanisms. Despite a disruption in a wide range of similar biological processes, the end result is very different: uncontrolled proliferation and early neurodegeneration. Thus, the links between the molecular mechanisms that cause PD and cancer remain to be elucidated. We propose that chronic inflammation in neurons and tumors contributes to a microenvironment that favors the accumulation of DNA mutations and facilitates disease formation. This article appraises the key role of microglia, establishes the genetic role of COX2 and CARD15 in PD and cancer, and discusses prevention and treatment with this new perspective in mind. We examine the evidence that chronic inflammation is an important link between cancer and PD.

  1. 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

  2. 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.

  3. Airway inflammation in nonobstructive and obstructive chronic bronchitis with chronic haemophilus influenzae airway infection. Comparison with noninfected patients with chronic obstructive pulmonary disease

    NARCIS (Netherlands)

    Bresser, P.; Out, T. A.; van Alphen, L.; Jansen, H. M.; Lutter, R.

    2000-01-01

    Nonencapsulated Haemophilus influenzae often causes chronic infections of the lower respiratory tract in both nonobstructive and obstructive chronic bronchitis. We assessed airway inflammation in clinically stable, chronically H. influenzae-infected patients with nonobstructive (CB-HI, n = 10) and

  4. Lipids, inflammation, and chronic kidney disease: a SHARP perspective.

    Science.gov (United States)

    Waters, David D; Vogt, Liffert

    2018-04-01

    Accumulating evidence indicates that inflammation plays a role in the initiation and progression of chronic kidney disease. In the Study of Heart and Renal Protection (SHARP) trial, higher baseline C-reactive protein and higher baseline low-density lipoprotein cholesterol levels were both associated with a higher risk of cardiovascular events, but higher baseline C-reactive protein levels were also associated with a higher risk of nonvascular events. Simvastatin/ezetimibe reduced cardiovascular events independent of baseline C-reactive protein levels. However, this observation does not exclude inflammation as a causal factor for cardiovascular disease development in chronic kidney disease patients. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  5. 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...

  6. Targeting pro-resolution pathways to combat chronic inflammation in COPD.

    Science.gov (United States)

    Bozinovski, Steven; Anthony, Desiree; Vlahos, Ross

    2014-11-01

    Chronic obstructive pulmonary disease (COPD) is an inflammatory lung condition that is associated with irreversible airflow obstruction as a consequence of small airways disease, excessive mucus production and emphysema. Paradoxically, excessive inflammation fails to control microbial pathogens that not only colonise COPD airways, but also trigger acute exacerbations, which markedly increase inflammation underlying host tissue damage. Excessive production of leukocyte mobilising cytokines such as CXCL8 (IL-8) and leukotriene B4 (LTB4) in response to environmental stimuli (cigarette smoke and microbial products) are thought to maintain chronic inflammation, in conjunction with inefficient macrophage clearance of microbes and apoptotic neutrophils. In this perspective, we discuss an alternative view on why inflammation persists with a focus on why pro-resolution mediators such as lipoxin A4 (LXA4), D-series resolving and Annexin A1 fail to effectively switch off inflammation in COPD. These pro-resolving mediators converge on the G-protein coupled receptor, ALX/FPR2. This receptor is particularly relevant to COPD as the complex milieu of exogenous and host-derived mediators within the inflamed airways include agonists that potently activate ALX/FPR2, including Serum Amyloid A (SAA) and the cathelicidin, LL-37. There is emerging evidence to suggest that ALX/FPR2 can exist in alternative receptor conformations in an agonist-biased manner, which facilitates alternate functional receptor behaviors. Hence, the development of more stable pro-resolving analogs provides therapeutic opportunities to address ALX/FPR2 conformations to counteract pathogenic signaling and promote non-phlogistic clearance pathways essential for resolution of inflammation.

  7. 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.

  8. A New Mouse Model That Spontaneously Develops Chronic Liver Inflammation and Fibrosis.

    Directory of Open Access Journals (Sweden)

    Nina Fransén-Pettersson

    Full Text Available Here we characterize a new animal model that spontaneously develops chronic inflammation and fibrosis in multiple organs, the non-obese diabetic inflammation and fibrosis (N-IF mouse. In the liver, the N-IF mouse displays inflammation and fibrosis particularly evident around portal tracts and central veins and accompanied with evidence of abnormal intrahepatic bile ducts. The extensive cellular infiltration consists mainly of macrophages, granulocytes, particularly eosinophils, and mast cells. This inflammatory syndrome is mediated by a transgenic population of natural killer T cells (NKT induced in an immunodeficient NOD genetic background. The disease is transferrable to immunodeficient recipients, while polyclonal T cells from unaffected syngeneic donors can inhibit the disease phenotype. Because of the fibrotic component, early on-set, spontaneous nature and reproducibility, this novel mouse model provides a unique tool to gain further insight into the underlying mechanisms mediating transformation of chronic inflammation into fibrosis and to evaluate intervention protocols for treating conditions of fibrotic disorders.

  9. 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.

  10. Modeling of chronic ovary inflammation

    Directory of Open Access Journals (Sweden)

    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

  11. 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.

  12. Social Isolation and Adult Mortality: The Role of Chronic Inflammation and Sex Differences

    Science.gov (United States)

    Yang, Yang Claire; McClintock, Martha K.; Kozloski, Michael; Li, Ting

    2014-01-01

    The health and survival benefits of social embeddedness have been widely documented across social species, but the underlying biophysiological mechanisms have not been elucidated in the general population. We assessed the process by which social isolation increases the risk for all-cause and chronic disease mortality through proinflammatory mechanisms. Using the 18-year mortality follow-up data (n = 6,729) from the National Health and Nutrition Examination Survey (1988–2006) on Social Network Index and multiple markers of chronic inflammation, we conducted survival analyses and found evidence that supports the mediation role of chronic inflammation in the link between social isolation and mortality. A high-risk fibrinogen level and cumulative inflammation burden may be particularly important in this link. There are notable sex differences in the mortality effects of social isolation in that they are greater for men and can be attributed in part to their heightened inflammatory responses. PMID:23653312

  13. 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

  14. 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 be...

  15. Low-grade chronic inflammation in the peripheral blood and ovaries of women with polycystic ovarian syndrome.

    Science.gov (United States)

    Xiong, Yong-lao; Liang, Xiao-yan; Yang, Xing; Li, Yi; Wei, Li-na

    2011-11-01

    The purpose of this study was to investigate chronic inflammation in the peripheral blood and ovaries of patients with polycystic ovary syndrome (PCOS). 86 PCOS patients and 50 controls were randomly enrolled in the study. Serum follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), blood routine test, lipid metabolism index, inflammation cytokines were detected. Ovary samples from PCOS group and control group were collected for macrophage and lymphocyte immunohistochemistry staining. Patients with PCOS showed significantly higher serum CRP, lymphocytes, monocytes, eosinophilic granulocytes, as well as higher triglycerides (TG), TNF-α and IL-6. PCOS ovary had greater number of macrophages and lymphocytes immersed throughout. In conclusion, PCOS patients exhibited hypertriglyceridemia and chronic inflammation, with elevated peripheral lymphocytes, monocytes, and eosinophilic granulocytes. In addition, their ovaries showed persistent chronic inflammation with a larger number of inflammatory cells immersed. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Ren, Zhenhua [Department of Anatomy, School of Basic Medicine, Anhui Medical University, Hefei, Anhui, China 230032 (China); Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536 (United States); Yang, Fanmuyi; Wang, Xin; Wang, Yongchao; Xu, Mei; Frank, Jacqueline A. [Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536 (United States); Ke, Zun-ji [Department of Biochemistry, Shanghai University of Traditional Chinese Medicine, Shanghai 201203 (China); Zhang, Zhuo; Shi, Xianglin [Department of Toxicology and Cancer Biology, University of Kentucky College of Medicine, Lexington, KY 40536 (United States); Luo, Jia, E-mail: jialuo888@uky.edu [Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536 (United States)

    2016-10-01

    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.

  18. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  20. Diet, inflammation, and chronic kidney disease: getting to the heart of the matter.

    Science.gov (United States)

    Neade, Tina; Uribarri, Jaime

    2008-01-01

    Cardiovascular disease (CVD) remains a leading cause of death in patients with chronic kidney disease (CKD). CVD is now thought to result from the interplay of several factors including inflammation, oxidative stress and endothelial dysfunction. Advanced glycation end products (AGE) are known to be elevated in patients with CKD and these compounds possess these pro-oxidant, pro-inflammatory and anti-endothelial properties. There has been a great deal of literature linking diet and inflammation, and recent work has shown the diet to be a significant contributor to the body's AGE pool. We herein hypothesize that a diet high in AGE plays an important role in the initiation of chronic subclinical inflammation that seems to underlie the high prevalence of CVD in CKD patients. Herein we will briefly examine the evidence linking different components of diet with inflammation in CKD patients. We will then focus on the role of dietary AGEs in inflammation and potentially CVD in CKD, and in conclusion, we will propose dietary modifications as part of a multifactorial approach to ameliorate unhealthy lifestyles among CKD patients. The most important message is that simple changes in culinary technique rather than in the food nutrient composition may be the most important part of preventing CVD in this population.

  1. Chronic prostatic infection and inflammation by Propionibacterium acnes in a rat prostate infection model.

    Science.gov (United States)

    Olsson, Jan; Drott, Johanna Bergh; Laurantzon, Lovisa; Laurantzon, Oscar; Bergh, Anders; Elgh, Fredrik

    2012-01-01

    Chronic inflammation in the prostate, seen as infiltration of inflammatory cells into the prostate gland in histological samples, affects approximately half the male population without indication of prostate disease, and is almost ubiquitous in patients diagnosed with benign prostate hyperplasia and cancer. Several studies have demonstrated the gram-positive bacterium Propionibacterium acnes to be frequently present in prostate tissue from men suffering from prostate disease. P. acnes has been shown to be associated with histological inflammation in human prostatectomy specimens, and also to induce strong inflammatory response in prostate-derived tissue culture models. The present paper describes a rat model for assessment of the pathogenic potential of P. acnes in prostate. Prostate glands of Sprague Dawley rats (n = 98) were exposed via an abdominal incision and live P. acnes or, in control rats, saline were injected into the ventral and dorso-lateral lobes. Rats were sacrificed 5 days, 3 weeks, 3 months and 6 months post infection, and prostate tissue was analyzed for bacterial content and histological inflammation. Rat sera were assessed for levels of CRP and anti-P. acnes IgG. Live P. acnes could be recovered from the dorso-lateral lobes up to 3 months post infection, while the ventral lobes were cleared from bacteria at that time. In samples up to 3 months post infection, the dorso-lateral lobes exhibited intense focal inflammation. CRP and IgG levels were elevated throughout the span of the experiment, and reached maximum levels 3 weeks and 3 months post infection, respectively. We show that P. acnes have the potential to cause chronic infection in previously healthy prostate, and that the infection has potential to cause chronic histological inflammation in the infected tissue. The high prevalence of P. acnes in human prostate tissue calls for resolution of pathogenic details. The present rat model suggests that complications such as chronic

  2. Maternal Income during Pregnancy is Associated with Chronic Placental Inflammation at Birth.

    Science.gov (United States)

    Keenan-Devlin, Lauren S; Ernst, Linda M; Ross, Kharah M; Qadir, Sameen; Grobman, William A; Holl, Jane L; Crockett, Amy; Miller, Gregory E; Borders, Ann E B

    2017-08-01

    Objective  This study aims to examine whether maternal household income is associated with histological evidence of chronic placental inflammation. Study Design  A total of 152 participants completed surveys of household income and consented to placenta collection at delivery and postpartum chart review for birth outcomes. Placental inflammatory lesions were evaluated via histological examination of the membranes, basal plate, and villous parenchyma by a single, experienced pathologist. Associations between household income and the presence of inflammatory lesions were adjusted for known perinatal risk factors. Results  Overall, 45% of participants reporting household income below $30,000/y had chronic placental inflammation, compared with 25% of participants reporting income above $100,000 annually (odds ratio [OR] = 4.23, 95% confidence interval [CI] = 1.25, 14.28; p  = 0.02). Middle-income groups showed intermediate rates of chronic inflammatory lesions, at 40% for those reporting $30,000 and 50,000 (OR = 3.60, 95% CI = 1.05, 12.53; p  = 0.04) and 38% for those reporting $50,000 to 100,000 (OR = 1.57, 95% CI = 0.60, 4.14; p  = 0.36). Results remained significant after adjustment for maternal age, race, and marital status. Conclusion  Chronic placental inflammation is associated with maternal household income. Greater occurrence of placental lesions in low-income mothers may arise from a systemic inflammatory response to social and physical environmental factors. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  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. Pulmonary Remodeling in Equine Asthma: What Do We Know about Mediators of Inflammation in the Horse?

    Science.gov (United States)

    Gehlen, Heidrun

    2016-01-01

    Equine inflammatory airway disease (IAD) and recurrent airway obstruction (RAO) represent a spectrum of chronic inflammatory disease of the airways in horses resembling human asthma in many aspects. Therefore, both are now described as severity grades of equine asthma. Increasing evidence in horses and humans suggests that local pulmonary inflammation is influenced by systemic inflammatory processes and the other way around. Inflammation, coagulation, and fibrinolysis as well as extracellular remodeling show close interactions. Cytology of bronchoalveolar lavage fluid and tracheal wash is commonly used to evaluate the severity of local inflammation in the lung. Other mediators of inflammation, like interleukins involved in the chemotaxis of neutrophils, have been studied. Chronic obstructive pneumopathies lead to remodeling of bronchial walls and lung parenchyma, ultimately causing fibrosis. Matrix metalloproteinases (MMPs) are discussed as the most important proteolytic enzymes during remodeling in human medicine and increasing evidence exists for the horse as well. A systemic involvement has been shown for severe equine asthma by increased acute phase proteins like serum amyloid A and haptoglobin in peripheral blood during exacerbation. Studies focusing on these and further possible inflammatory markers for chronic respiratory disease in the horse are discussed in this review of the literature. PMID:28053371

  5. 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.

  6. Reversal of acute and chronic synovial inflammation by anti-transforming growth factor beta.

    Science.gov (United States)

    Wahl, S M; Allen, J B; Costa, G L; Wong, H L; Dasch, J R

    1993-01-01

    Transforming growth factor beta (TGF-beta) induces leukocyte recruitment and activation, events central to an inflammatory response. In this study, we demonstrate that antagonism of TGF-beta with a neutralizing antibody not only blocks inflammatory cell accumulation, but also tissue pathology in an experimental model of chronic erosive polyarthritis. Intraarticular injection of monoclonal antibody 1D11.16, which inhibits both TGF-beta 1 and TGF-beta 2 bioactivity, into animals receiving an arthropathic dose of bacterial cell walls significantly inhibits arthritis. Inhibition was observed with a single injection of 50 micrograms antibody, and a 1-mg injection blocked acute inflammation > 75% compared with the contralateral joints injected with an irrelevant isotype control antibody (MOPC21) as quantitated by an articular index (AI = 0.93 +/- 0.23 for 1D11.16, and AI = 4.0 +/- 0 on day 4; p histopathologic and radiologic evidence of a therapeutic response. These data implicate TGF-beta as a profound agonist not only in the early events responsible for synovial inflammation, but also in the chronicity of streptococcal cell wall fragment-induced inflammation culminating in destructive pathology. Interrupting the cycle of leukocyte recruitment and activation with TGF-beta antagonists may provide a mechanism for resolution of chronic destructive lesions.

  7. 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 ...

  8. Mediators of low-grade chronic inflammation in polycystic ovary syndrome (PCOS).

    Science.gov (United States)

    Ojeda-Ojeda, Miriam; Murri, Mora; Insenser, María; Escobar-Morreale, Héctor F

    2013-01-01

    Chronic low-grade subclinical inflammation has been increasingly recognized as an interposer in the endocrine, metabolic and reproductive disturbances that characterize the polycystic ovary syndrome (PCOS). Abdominal adiposity and obesity are often present in PCOS. Mounting evidence indicates that adipose tissue is involved in innate and adaptive immune responses. Continuous release of inflammatory mediators such as cytokines, acute phase proteins, and adipokines perpetuates the inflammatory condition associated with obesity in women with PCOS, possibly contributing to insulin resistance and other long-term cardiometabolic risk factors. Genetic variants in the genes encoding inflammation-related mediators underlie the development of PCOS and their interaction with environmental factors may contribute to the heterogeneous clinical phenotype of this syndrome. In the future, strategies ameliorating inflammation may prove useful for the management of PCOS and associated conditions.

  9. 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.

  10. Transient infection of the zebrafish notochord with E. coli induces chronic inflammation

    Directory of Open Access Journals (Sweden)

    Mai Nguyen-Chi

    2014-07-01

    Full Text Available Zebrafish embryos and larvae are now well-established models in which to study infectious diseases. Infections with non-pathogenic Gram-negative Escherichia coli induce a strong and reproducible inflammatory response. Here, we study the cellular response of zebrafish larvae when E. coli bacteria are injected into the notochord and describe the effects. First, we provide direct evidence that the notochord is a unique organ that is inaccessible to leukocytes (macrophages and neutrophils during the early stages of inflammation. Second, we show that notochord infection induces a host response that is characterised by rapid clearance of the bacteria, strong leukocyte recruitment around the notochord and prolonged inflammation that lasts several days after bacteria clearance. During this inflammatory response, il1b is first expressed in macrophages and subsequently at high levels in neutrophils. Moreover, knock down of il1b alters the recruitment of neutrophils to the notochord, demonstrating the important role of this cytokine in the maintenance of inflammation in the notochord. Eventually, infection of the notochord induces severe defects of the notochord that correlate with neutrophil degranulation occurring around this tissue. This is the first in vivo evidence that neutrophils can degranulate in the absence of a direct encounter with a pathogen. Persistent inflammation, neutrophil infiltration and restructuring of the extracellular matrix are defects that resemble those seen in bone infection and in some chondropathies. As the notochord is a transient embryonic structure that is closely related to cartilage and bone and that contributes to vertebral column formation, we propose infection of the notochord in zebrafish larvae as a new model to study the cellular and molecular mechanisms underlying cartilage and bone inflammation.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Apple Polysaccharide inhibits microbial dysbiosis and chronic inflammation and modulates gut permeability in HFD-fed rats.

    Science.gov (United States)

    Wang, Sheng; Li, Qian; Zang, Yue; Zhao, Yang; Liu, Nan; Wang, Yifei; Xu, Xiaotao; Liu, Li; Mei, Qibing

    2017-06-01

    The saying "An apple a day keeps the doctor away" has been known for over 150 years, and numerous studies have shown that apple consumption is closely associated with reduced risks of chronic diseases. It has been well accepted that dysbiosis is the reflection of various chronic diseases. Therefore, this study investigates the effects of apple polysaccharides (AP) on gut dysbiosis. High-fat diet (HFD) fed rats were treated for 14 weeks with AP. The microbiota composition, microbiota-generated short chain fatty acids (SCFAs), gut permeability and chronic inflammation were analyzed. AP treatment showed higher abundance of Bacteroidetes and Lactobacillus while lower Firmicutes and Fusobacteium. AP significantly increased total SCFAs level that contributed by acetic acid and isobutyric acid. Moreover, AP dramatically alleviated dysbiosis-associated gut permeability and chronic inflammation with decreased plasma LBP, up-regulation of Occludin, down-regulation of tumor necrosis factor a (TNF-a), monocyte chemotactic protein 1 (MCP-1), chemokine ligand 1 (CXCL-1) and interleukin 1 beta (IL-1β). The potential mechanism is due to the fact that AP reduces gut permeability, which involves the induction of autophagy in goblet cells. Therefore, AP exerts health benefits through inhibiting gut dysbiosis and chronic inflammation and modulating gut permeability in HFD-induced dysbiosis rats. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. The Emerging Role of Chronic Low-Grade Inflammation in the Pathophysiology of Polycystic Ovary Syndrome.

    Science.gov (United States)

    Shorakae, Soulmaz; Teede, Helena; de Courten, Barbora; Lambert, Gavin; Boyle, Jacqueline; Moran, Lisa J

    2015-07-01

    Polycystic ovary syndrome (PCOS) has become increasingly common over recent years and is associated with reproductive features as well as cardiometabolic risk factors, including visceral obesity, dyslipidemia and impaired glucose homeostasis, and potentially cardiovascular disease. Emerging evidence suggests that these long-term metabolic effects are linked to a low-grade chronic inflammatory state with the triad of hyperinsulinemia, hyperandrogenism, and low-grade inflammation acting together in a vicious cycle in the pathophysiology of PCOS. Dysregulation of the sympathetic nervous system may also act as an important component, potentially creating a tetrad in the pathophysiology of PCOS. The aim of this review is to examine the role of chronic inflammation and the sympathetic nervous system in the development of obesity and PCOS and review potential therapeutic options to alleviate low-grade inflammation in this setting. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  14. Transient infection of the zebrafish notochord with E. coli induces chronic inflammation.

    Science.gov (United States)

    Nguyen-Chi, Mai; Phan, Quang Tien; Gonzalez, Catherine; Dubremetz, Jean-François; Levraud, Jean-Pierre; Lutfalla, Georges

    2014-07-01

    Zebrafish embryos and larvae are now well-established models in which to study infectious diseases. Infections with non-pathogenic Gram-negative Escherichia coli induce a strong and reproducible inflammatory response. Here, we study the cellular response of zebrafish larvae when E. coli bacteria are injected into the notochord and describe the effects. First, we provide direct evidence that the notochord is a unique organ that is inaccessible to leukocytes (macrophages and neutrophils) during the early stages of inflammation. Second, we show that notochord infection induces a host response that is characterised by rapid clearance of the bacteria, strong leukocyte recruitment around the notochord and prolonged inflammation that lasts several days after bacteria clearance. During this inflammatory response, il1b is first expressed in macrophages and subsequently at high levels in neutrophils. Moreover, knock down of il1b alters the recruitment of neutrophils to the notochord, demonstrating the important role of this cytokine in the maintenance of inflammation in the notochord. Eventually, infection of the notochord induces severe defects of the notochord that correlate with neutrophil degranulation occurring around this tissue. This is the first in vivo evidence that neutrophils can degranulate in the absence of a direct encounter with a pathogen. Persistent inflammation, neutrophil infiltration and restructuring of the extracellular matrix are defects that resemble those seen in bone infection and in some chondropathies. As the notochord is a transient embryonic structure that is closely related to cartilage and bone and that contributes to vertebral column formation, we propose infection of the notochord in zebrafish larvae as a new model to study the cellular and molecular mechanisms underlying cartilage and bone inflammation. © 2014. Published by The Company of Biologists Ltd.

  15. Modulation of hepatic inflammation and energy-sensing pathways in the rat liver by high-fructose diet and chronic stress.

    Science.gov (United States)

    Veličković, Nataša; Teofilović, Ana; Ilić, Dragana; Djordjevic, Ana; Vojnović Milutinović, Danijela; Petrović, Snježana; Preitner, Frederic; Tappy, Luc; Matić, Gordana

    2018-05-29

    High-fructose consumption and chronic stress are both associated with metabolic inflammation and insulin resistance. Recently, disturbed activity of energy sensor AMP-activated protein kinase (AMPK) was recognized as mediator between nutrient-induced stress and inflammation. Thus, we analyzed the effects of high-fructose diet, alone or in combination with chronic stress, on glucose homeostasis, inflammation and expression of energy sensing proteins in the rat liver. In male Wistar rats exposed to 9-week 20% fructose diet and/or 4-week chronic unpredictable stress we measured plasma and hepatic corticosterone level, indicators of glucose homeostasis and lipid metabolism, hepatic inflammation (pro- and anti-inflammatory cytokine levels, Toll-like receptor 4, NLRP3, activation of NFκB, JNK and ERK pathways) and levels of energy-sensing proteins AMPK, SIRT1 and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α). High-fructose diet led to glucose intolerance, activation of NFκB and JNK pathways and increased intrahepatic IL-1β, TNFα and inhibitory phosphorylation of insulin receptor substrate 1 on Ser 307 . It also decreased phospho-AMPK/AMPK ratio and increased SIRT1 expression. Stress alone increased plasma and hepatic corticosterone but did not influence glucose tolerance, nor hepatic inflammatory or energy-sensing proteins. After the combined treatment, hepatic corticosterone was increased, glucose tolerance remained preserved, while hepatic inflammation was partially prevented despite decreased AMPK activity. High-fructose diet resulted in glucose intolerance, hepatic inflammation, decreased AMPK activity and reduced insulin sensitivity. Chronic stress alone did not exert such effects, but when applied together with high-fructose diet it could partially prevent fructose-induced inflammation, presumably due to increased hepatic glucocorticoids.

  16. [Chronic low-grade inflammation, lipid risk factors and mortality in functionally dependent elderly].

    Science.gov (United States)

    Vasović, Olga; Trifunović, Danijela; Despotovié, Nebojsa; Milosević, Dragoslav P

    2010-07-01

    It has been proved that a highly sensitive C-reactive protein (hsCRP) can be used as an established marker of chronic inflammation for cardiovascular risk assessment. Since mean values of both low-density cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) decrease during aging, the knowledge that increased hsCRP concentration predicts mortality (Mt) would influence therapy and treatment outcome. The aim of this study was to examine importance of chronic low grade inflammation and its association with lipid risk factors for all-cause Mt in functionally dependent elderly. The participants of this longitudinal prospective study were 257 functionally dependent elderly aged 65-99 years. Baseline measurements: anthropometric measurements, blood pressure, fasting plasma total cholesterol (TC), triglyceride (TG), HDL-C, LDL-C, non-HDL-C, hemoglobin Alc (HbA1c) were recorded and different lipid ratios were calculated. Inflammation was assessed by the levels of white blood cells, fibrinogen and hsCRP. The participants with hsCRP grater than 10 mg/L were excluded from the study. The residual participants (77.4% women) were divided into three groups according to their hsCRP levels: a low (agressive lipid lowering treatment.

  17. Monocyte and plasma expression of TAM ligand and receptor in renal failure: Links to unregulated immunity and chronic inflammation.

    Science.gov (United States)

    Lee, Iris J; Hilliard, Brendan A; Ulas, Mehriban; Yu, Daohai; Vangala, Chandan; Rao, Swati; Lee, Jean; Gadegbeku, Crystal A; Cohen, Philip L

    2015-06-01

    Chronic inflammation is increased in patients with chronic kidney disease (CKD) and contributes to cardiovascular morbidity and mortality. Specific immune mechanisms and pathways that drive and maintain chronic inflammation in CKD are not well described. The TAM ligands (Gas6 and protein S) and receptors (Axl and Mer) have been recently recognized as playing a prominent role in immune regulation. The receptors exist in both soluble and cell-bound forms; the soluble receptors (sAxl and sMer) are believed to compete with the bound receptors and thus inhibit their function. In this study, we determined the expression of cell-bound and soluble TAM proteins in patients with CKD. CKD patients had significantly lower expression of Mer in monocytes, yet increased expression of soluble TAM receptors sAxl and sMer in plasma compared to controls. The metalloproteinase ADAM 17, responsible for cleavage of Mer to its soluble form, was increased in patient monocytes. Elevated levels of soluble TAM receptors were more evident in patients with progressive renal failure. These observations suggest that functional deficiency of TAM receptor-mediated regulation of inflammation may contribute to chronic inflammation in patients with CKD. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Loss of hepatocyte-nuclear-factor-4alpha affects colonic ion transport and causes chronic inflammation resembling inflammatory bowel disease in mice.

    Directory of Open Access Journals (Sweden)

    Mathieu Darsigny

    Full Text Available BACKGROUND: Hnf4alpha, an epithelial specific transcriptional regulator, is decreased in inflammatory bowel disease and protects against chemically-induced colitis in mice. However, the precise role of this factor in maintaining normal inflammatory homeostasis of the intestine remains unclear. The aim of this study was to evaluate the sole role of epithelial Hnf4alpha in the maintenance of gut inflammatory homeostasis in mice. METHODOLOGY/PRINCIPAL FINDINGS: We show here that specific epithelial deletion of Hnf4alpha in mice causes spontaneous chronic intestinal inflammation leading to focal areas of crypt dropout, increased cytokines and chemokines secretion, immune cell infiltrates and crypt hyperplasia. A gene profiling analysis in diseased Hnf4alpha null colon confirms profound genetic changes in cell death and proliferative behaviour related to cancer. Among the genes involved in the immune protection through epithelial barrier function, we identify the ion transporter claudin-15 to be down-modulated early in the colon of Hnf4alpha mutants. This coincides with a significant decrease of mucosal ion transport but not of barrier permeability in young animals prior to the manifestation of the disease. We confirm that claudin-15 is a direct Hnf4alpha gene target in the intestinal epithelial context and is down-modulated in mouse experimental colitis and inflammatory bowel disease. CONCLUSION: Our results highlight the critical role of Hnf4alpha to maintain intestinal inflammatory homeostasis during mouse adult life and uncover a novel function for Hnf4alpha in the regulation of claudin-15 expression. This establishes Hnf4alpha as a mediator of ion epithelial transport, an important process for the maintenance of gut inflammatory homeostasis.

  19. Dietary supplementation of resveratrol attenuates chronic colonic inflammation in mice.

    Science.gov (United States)

    Sánchez-Fidalgo, Susana; Cárdeno, Ana; Villegas, Isabel; Talero, Elena; de la Lastra, Catalina Alarcón

    2010-05-10

    Ulcerative colitis is a nonspecific inflammatory disorder characterized by oxidative and nitrosative stress, leucocyte infiltration and upregulation of inflammatory mediators. Resveratrol is a polyphenolic compound found in grapes and wine, with multiple pharmacological actions, mainly anti-inflammatory, antioxidant, antitumour and immunomodulatory activities. The aim of this study was to investigate the effect of dietary resveratrol on chronic dextran sulphate sodium (DSS)-induced colitis. Six-week-old mice were randomized into two dietary groups: one standard diet and the other enriched with resveratrol at 20mg/kg of diet. After 30days, mice were exposed to 3% DSS for 5days developing acute colitis that progressed to severe chronic inflammation after 21days of water. Our results demonstrated that resveratrol group significantly attenuated the clinical signs such as loss of body weight, diarrhea and rectal bleeding improving results from disease activity index and inflammatory score. Moreover, the totality of resveratrol-fed animals survived and finished the treatment while animals fed with standard diet showed a mortality of 40%. Three weeks after DSS removal, the polyphenol caused substantial reductions of the rise of pro-inflammatory cytokines, TNF-alpha and IL-1beta and an increase of the anti-inflammatory cytokine IL-10. Also resveratrol reduced prostaglandin E synthase-1 (PGES-1), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) proteins expression, via downregulation of p38, a mitogen-activated protein kinases (MAPK) signal pathway. We conclude that resveratrol diet represents a novel approach to the treatment of chronic intestinal inflammation. Copyright 2010 Elsevier B.V. All rights reserved.

  20. Airway inflammation in chronic obstructive pulmonary disease (COPD): a true paradox.

    Science.gov (United States)

    Eapen, Mathew Suji; Myers, Stephen; Walters, Eugene Haydn; Sohal, Sukhwinder Singh

    2017-10-01

    Chronic obstructive pulmonary disease (COPD) is primarily an airway condition, which mainly affects cigarette smokers and presents with shortness of breath that is progressive and poorly reversible. In COPD research, there has been a long held belief that airway disease progression is due to inflammation. Although this may be true in the airway lumen with innate immunity activated by the effect of smoke or secondary to infection, the accurate picture of inflammatory cells in the airway wall, where the pathophysiological COPD remodeling occurs, is uncertain and debatable. Areas covered: The current review provides a comprehensive literature survey of the changes in the main inflammatory cells in human COPD patients and focuses on contrarian views that affect the prevailing dogma on inflammation. The review also delves into the role of oxidative stress and inflammasomes in modulating the immune response in COPD. Further, the effects of inflammation in affecting the epithelium, fibroblasts, and airway remodeling are discussed. Expert commentary: Inflammation as a driving force for airway wall damage and remodelling in early COPD is at the very least 'oversimplified' and is likely to be misleading. This has serious implications for rational thinking about the illness, including pathogenesis and designing therapy.

  1. Prostate cancer and inflammation: the evidence

    OpenAIRE

    Sfanos, Karen S; De Marzo, Angelo M

    2012-01-01

    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 prosta...

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

    OpenAIRE

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

    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...

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

    International Nuclear Information System (INIS)

    Takx, Richard A.P.; MacNabb, Megan H.; Emami, Hamed; Abdelbaky, Amr; Lavender, Zachary R.; Singh, Parmanand; Di Carli, Marcelo; Taqueti, Viviany; Foster, Courtney; Mann, Jessica; Comley, Robert A.; Weber, Chek Ing Kiu; Tawakol, Ahmed

    2016-01-01

    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 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 cardiovascular

  4. 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

  5. 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....... In a rat model of acute P. aeruginosa pneumonia we studied whether it was possible to improve the initial bacterial clearance and diminish the inflammatory response by vaccination prior to challenge with free, live P. aeruginosa. The vaccines studied were PAO 579 sonicate, O-polysaccharide toxin A (TA...

  6. 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

  7. 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.

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

    Directory of Open Access Journals (Sweden)

    Liana Verinaud

    Full Text Available Inflammation is a necessary process to control infection. However, exacerbated inflammation, acute or chronic, promotes deleterious effects in the organism. Violacein (viola, a quorum sensing metabolite from the Gram-negative bacterium Chromobacterium violaceum, has been shown to protect mice from malaria and to have beneficial effects on tumors. However, it is not known whether this drug possesses anti-inflammatory activity. In this study, we investigated whether viola administration is able to reduce acute and chronic autoimmune inflammation. For that purpose, C57BL/6 mice were intraperitoneally injected with 1 μg of LPS and were treated with viola (3.5mg/kg via i.p. at the same time-point. Three hours later, the levels of inflammatory cytokines in the sera and phenotypical characterization of leukocytes were determined. Mice treated with viola presented a significant reduction in the production of inflammatory cytokines compared with untreated mice. Interestingly, although viola is a compound derived from bacteria, it did not induce inflammation upon administration to naïve mice. To test whether viola would protect mice from an autoimmune inflammation, Experimental Autoimmune Encephalomyelitis (EAE-inflicted mice were given viola i.p. at disease onset, at the 10th day from immunization. Viola-treated mice developed mild EAE disease in contrast with placebo-treated mice. The frequencies of dendritic cells and macrophages were unaltered in EAE mice treated with viola. However, the sole administration of viola augmented the levels of splenic regulatory T cells (CD4+Foxp3+. We also found that adoptive transfer of viola-elicited regulatory T cells significantly reduced EAE. Our study shows, for the first time, that violacein is able to modulate acute and chronic inflammation. Amelioration relied in suppression of cytokine production (in acute inflammation and stimulation of regulatory T cells (in chronic inflammation. New studies must be

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Suppression of skin inflammation in keratinocytes and acute/chronic disease models by caffeic acid phenethyl ester.

    Science.gov (United States)

    Lim, Kyung-Min; Bae, SeungJin; Koo, Jung Eun; Kim, Eun-Sun; Bae, Ok-Nam; Lee, Joo Young

    2015-04-01

    Skin inflammation plays a central role in the pathophysiology and symptoms of diverse chronic skin diseases including atopic dermatitis (AD). In this study, we examined if caffeic acid phenethyl ester (CAPE), a skin-permeable bioactive compound from propolis, was protective against skin inflammation using in vitro cell system and in vivo animal disease models. CAPE suppressed TNF-α-induced NF-κB activation and expression of inflammatory cytokines in human keratinocytes (HaCaT). The potency and efficacy of CAPE were superior to those of a non-phenethyl derivative, caffeic acid. Consistently, topical treatment of CAPE (0.5 %) attenuated 12-O-tetradecanoylphorbol-13-acetate(TPA)-induced skin inflammation on mouse ear as CAPE reduced ear swelling and histologic inflammation scores. CAPE suppressed increased expression of pro-inflammatory molecules such as TNF-α, cyclooxygenase-2 and inducible NO synthase in TPA-stimulated skin. TPA-induced phosphorylation of IκB and ERK was blocked by CAPE suggesting that protective effects of CAPE on skin inflammation is attributed to inhibition of NF-κB activation. Most importantly, in an oxazolone-induced chronic dermatitis model, topical application of CAPE (0.5 and 1 %) was effective in alleviating AD-like symptoms such as increases of trans-epidermal water loss, skin thickening and serum IgE as well as histologic inflammation assessment. Collectively, our results propose CAPE as a promising candidate for a novel topical drug for skin inflammatory diseases.

  11. Concurrent Social Disadvantages and Chronic Inflammation: The Intersection of Race and Ethnicity, Gender, and Socioeconomic Status.

    Science.gov (United States)

    Richman, Aliza D

    2017-08-28

    Disadvantaged social statuses, such as being female, poor, or a minority, are associated with increased psychosocial stress and elevated circulating concentrations of C-reactive protein, a biomarker of chronic inflammation and indicator of cardiovascular health. Individuals' experience of embodying psychosocial stress revolves around the multiplicative effects of concurrent gender, socioeconomic, and racial and ethnic identities. This study expands on prior research by examining chronic inflammation at the intersection of race and ethnicity, gender, socioeconomic status, and age group to understand which demographic subgroups in society are most vulnerable to the cumulative effects of social disadvantage. Using data from the National Health and Nutrition Examination Survey 2007-2010, the findings reveal inflammation disparities between non-poor whites and the following demographic subgroups, net of sociodemographic and biological factors: young poor Hispanic women, young poor white men, young poor and non-poor Hispanic men, middle-aged poor and non-poor black women, middle-aged poor and non-poor black men, and middle-aged poor Hispanic men. Disparities in inflammation on account of social disadvantage are most evident among those aged 45-64 years and diminish for those 65 and older in both men and women.

  12. Aberrant mucin assembly in mice causes endoplasmic reticulum stress and spontaneous inflammation resembling ulcerative colitis.

    Directory of Open Access Journals (Sweden)

    Chad K Heazlewood

    2008-03-01

    Full Text Available MUC2 mucin produced by intestinal goblet cells is the major component of the intestinal mucus barrier. The inflammatory bowel disease ulcerative colitis is characterized by depleted goblet cells and a reduced mucus layer, but the aetiology remains obscure. In this study we used random mutagenesis to produce two murine models of inflammatory bowel disease, characterised the basis and nature of the inflammation in these mice, and compared the pathology with human ulcerative colitis.By murine N-ethyl-N-nitrosourea mutagenesis we identified two distinct noncomplementing missense mutations in Muc2 causing an ulcerative colitis-like phenotype. 100% of mice of both strains developed mild spontaneous distal intestinal inflammation by 6 wk (histological colitis scores versus wild-type mice, p < 0.01 and chronic diarrhoea. Monitoring over 300 mice of each strain demonstrated that 25% and 40% of each strain, respectively, developed severe clinical signs of colitis by age 1 y. Mutant mice showed aberrant Muc2 biosynthesis, less stored mucin in goblet cells, a diminished mucus barrier, and increased susceptibility to colitis induced by a luminal toxin. Enhanced local production of IL-1beta, TNF-alpha, and IFN-gamma was seen in the distal colon, and intestinal permeability increased 2-fold. The number of leukocytes within mesenteric lymph nodes increased 5-fold and leukocytes cultured in vitro produced more Th1 and Th2 cytokines (IFN-gamma, TNF-alpha, and IL-13. This pathology was accompanied by accumulation of the Muc2 precursor and ultrastructural and biochemical evidence of endoplasmic reticulum (ER stress in goblet cells, activation of the unfolded protein response, and altered intestinal expression of genes involved in ER stress, inflammation, apoptosis, and wound repair. Expression of mutated Muc2 oligomerisation domains in vitro demonstrated that aberrant Muc2 oligomerisation underlies the ER stress. In human ulcerative colitis we demonstrate similar

  13. Cholera toxin B subunit labeling in lamina II of spinal cord dorsal horn following chronic inflammation in rats.

    Science.gov (United States)

    Ma, Qing Ping; Tian, Li

    2002-07-26

    We have investigated the effect of inflammation on the labeling pattern of cholera toxin B subunit (CTB)-conjugated horseradish peroxidase, an A-fiber marker, by an intra-sciatic nerve injection of the tracer. Following chronic inflammation in one hind paw in rats, there was substantial CTB labeling in lamina II of the spinal dorsal horn, which is normally absent. However, there was no change in the labeling pattern of wheat germ agglutinin or fluoride resistant acid phosphatase/thiamine monophosphatase, two C-fiber markers. The CTB labeling in lamina II after peripheral nerve injury has been interpreted as central sprouting of A-fibers or uptake of the tracer by injured C-fibers. Our results suggest that chronic inflammation and nerve injury may share some common mechanisms in generating allodynia and hyperalgesia.

  14. 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.

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

    Science.gov (United States)

    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.

  16. The role of vitamin K in chronic aging diseases: inflammation, cardiovascular disease and osteoarthritis

    Science.gov (United States)

    Vitamin K is an enzyme cofactor required for the carboxylation of vitamin K dependent proteins, several of which have been implicated in diseases of aging. Inflammation is recognized as a crucial component of many chronic aging diseases, and evidence suggests vitamin K has an anti-inflammatory actio...

  17. 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

  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

    Directory of Open Access Journals (Sweden)

    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. Detection of systemic inflammation in severely impaired chronic pain patients, and effects of a CBT-ACT-based multi-modal pain rehabilitation program.

    Science.gov (United States)

    Hysing, E-B; Smith, L; Thulin, M; Karlsten, R; Gordh, T

    2017-12-29

    Aims A few previous studies indicate an ongoing of low-grade systemic inflammation in chronic pain patients (CPP) [1, 2]. In the present study we investigated the plasma inflammatory profile in severely impaired chronic pain patients. In addition we studied if there were any alterations in inflammation patterns at one-year follow up, after the patients had taken part in a CBT-ACT based 4 weeks in-hospital pain rehabilitation program (PRP). Methods Blood samples were collected from 52 well characterized chronic pain patients. Plasma from matched healthy blood donors were used as controls. At one year after the treatment program, 28 of the patients were available for follow up. Instead of only analyzing single inflammation-related substances, we used a new multiplex panel enabling the simultaneous analysis of 92 inflammation-related proteins, mainly cytokines and chemokines (Proseek Inflammation, Olink, Uppsala, Sweden). Multivariate statistics were used for analysis. Results Clear signs of increased inflammatory activity were detected in the pain patients. Accepting a false discovery rate (FDR) of 5%, there were significant differences in 43 of the 92 inflammatory biomarkers. The expression of 8 biomarkers were 4 times higher in patients compared to controls. Three biomarkers, CXCL5, SIRT2, AXIN1 were more than 8 times higher. The conventional marker for inflammation, CRP, did not differ. Of the 28 patients available for follow up one year after the intervention, all showed lower levels of the inflammatory biomarker initially raised. Conclusions The results indicate that CPP suffer from a low grade of chronic systemic inflammation, not detectable by CRP analysis. This may have implications for the general pain hypersensitivity, and other symptoms, often described in this group of patients. We conclude that inflammatory plasma proteins may be measureable molecular markers to distinguishes CPP from pain free controls, and that a CBT-ACT pain rehab program seem to

  20. 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......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......-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...

  1. Chronic Oxidative Stress, Mitochondrial Dysfunction, Nrf2 Activation and Inflammation in the Hippocampus Accompany Heightened Systemic Inflammation and Oxidative Stress in an Animal Model of Gulf War Illness

    Science.gov (United States)

    Shetty, Geetha A.; Hattiangady, Bharathi; Upadhya, Dinesh; Bates, Adrian; Attaluri, Sahithi; Shuai, Bing; Kodali, Maheedhar; Shetty, Ashok K.

    2017-01-01

    Memory and mood dysfunction are the key symptoms of Gulf war illness (GWI), a lingering multi-symptom ailment afflicting >200,000 veterans who served in the Persian Gulf War-1. Research probing the source of the disease has demonstrated that concomitant exposures to anti-nerve gas agent pyridostigmine bromide (PB), pesticides, and war-related stress are among the chief causes of GWI. Indeed, exposures to GWI-related chemicals (GWIR-Cs) and mild stress in animal models cause memory and mood impairments alongside reduced neurogenesis and chronic low-level inflammation in the hippocampus. In the current study, we examined whether exposure to GWIR-Cs and stress causes chronic changes in the expression of genes related to increased oxidative stress, mitochondrial dysfunction, and inflammation in the hippocampus. We also investigated whether GWI is linked with chronically increased activation of Nrf2 (a master regulator of antioxidant response) in the hippocampus, and inflammation and enhanced oxidative stress at the systemic level. Adult male rats were exposed daily to low-doses of PB and pesticides (DEET and permethrin), in combination with 5 min of restraint stress for 4 weeks. Analysis of the hippocampus performed 6 months after the exposure revealed increased expression of many genes related to oxidative stress response and/or antioxidant activity (Hmox1, Sepp1, and Srxn1), reactive oxygen species metabolism (Fmo2, Sod2, and Ucp2) and oxygen transport (Ift172 and Slc38a1). Furthermore, multiple genes relevant to mitochondrial respiration (Atp6a1, Cox6a1, Cox7a2L, Ndufs7, Ndufv1, Lhpp, Slc25a10, and Ucp1) and neuroinflammation (Nfkb1, Bcl6, Csf2, IL6, Mapk1, Mapk3, Ngf, N-pac, and Prkaca) were up-regulated, alongside 73–88% reduction in the expression of anti-inflammatory genes IL4 and IL10, and nuclear translocation and increased expression of Nrf2 protein. These hippocampal changes were associated with elevated levels of pro-inflammatory cytokines and chemokines

  2. Chronic Oxidative Stress, Mitochondrial Dysfunction, Nrf2 Activation and Inflammation in the Hippocampus Accompany Heightened Systemic Inflammation and Oxidative Stress in an Animal Model of Gulf War Illness.

    Science.gov (United States)

    Shetty, Geetha A; Hattiangady, Bharathi; Upadhya, Dinesh; Bates, Adrian; Attaluri, Sahithi; Shuai, Bing; Kodali, Maheedhar; Shetty, Ashok K

    2017-01-01

    Memory and mood dysfunction are the key symptoms of Gulf war illness (GWI), a lingering multi-symptom ailment afflicting >200,000 veterans who served in the Persian Gulf War-1. Research probing the source of the disease has demonstrated that concomitant exposures to anti-nerve gas agent pyridostigmine bromide (PB), pesticides, and war-related stress are among the chief causes of GWI. Indeed, exposures to GWI-related chemicals (GWIR-Cs) and mild stress in animal models cause memory and mood impairments alongside reduced neurogenesis and chronic low-level inflammation in the hippocampus. In the current study, we examined whether exposure to GWIR-Cs and stress causes chronic changes in the expression of genes related to increased oxidative stress, mitochondrial dysfunction, and inflammation in the hippocampus. We also investigated whether GWI is linked with chronically increased activation of Nrf2 (a master regulator of antioxidant response) in the hippocampus, and inflammation and enhanced oxidative stress at the systemic level. Adult male rats were exposed daily to low-doses of PB and pesticides (DEET and permethrin), in combination with 5 min of restraint stress for 4 weeks. Analysis of the hippocampus performed 6 months after the exposure revealed increased expression of many genes related to oxidative stress response and/or antioxidant activity ( Hmox1, Sepp1 , and Srxn1 ), reactive oxygen species metabolism ( Fmo2, Sod2 , and Ucp2 ) and oxygen transport ( Ift172 and Slc38a1 ). Furthermore, multiple genes relevant to mitochondrial respiration ( Atp6a1, Cox6a1, Cox7a2L, Ndufs7, Ndufv1, Lhpp, Slc25a10 , and Ucp1 ) and neuroinflammation ( Nfkb1, Bcl6, Csf2, IL6, Mapk1, Mapk3, Ngf, N-pac , and Prkaca ) were up-regulated, alongside 73-88% reduction in the expression of anti-inflammatory genes IL4 and IL10 , and nuclear translocation and increased expression of Nrf2 protein. These hippocampal changes were associated with elevated levels of pro-inflammatory cytokines

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  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

    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. 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.

  7. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Chronic intermittent hypoxia induces cardiac inflammation and dysfunction in a rat obstructive sleep apnea model.

    Science.gov (United States)

    Wei, Qin; Bian, Yeping; Yu, Fuchao; Zhang, Qiang; Zhang, Guanghao; Li, Yang; Song, Songsong; Ren, Xiaomei; Tong, Jiayi

    2016-11-01

    Chronic intermittent hypoxia is considered to play an important role in cardiovascular pathogenesis during the development of obstructive sleep apnea (OSA). We used a well-described OSA rat model induced with simultaneous intermittent hypoxia. Male Sprague Dawley rats were individually placed into plexiglass chambers with air pressure and components were electronically controlled. The rats were exposed to intermittent hypoxia 8 hours daily for 5 weeks. The changes of cardiac structure and function were examined by ultrasound. The cardiac pathology, apoptosis, and fibrosis were analyzed by H&E staining, TUNNEL assay, and picosirius staining, respectively. The expression of inflammation and fibrosis marker genes was analyzed by quantitative real-time PCR and Western blot. Chronic intermittent hypoxia/low pressure resulted in significant increase of left ventricular internal diameters (LVIDs), end-systolic volume (ESV), end-diastolic volume (EDV), and blood lactate level and marked reduction in ejection fraction and fractional shortening. Chronic intermittent hypoxia increased TUNNEL-positive myocytes, disrupted normal arrangement of cardiac fibers, and increased Sirius stained collagen fibers. The expression levels of hypoxia induced factor (HIF)-1α, NF-kB, IL-6, and matrix metallopeptidase 2 (MMP-2) were significantly increased in the heart of rats exposed to chronic intermittent hypoxia. In conclusion, the left ventricular function was adversely affected by chronic intermittent hypoxia, which is associated with increased expression of HIF-1α and NF-kB signaling molecules and development of cardiac inflammation, apoptosis and fibrosis. © 2016 by the Journal of Biomedical Research. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Leprae reaction resembling rheumatologic disease as presenting feature of leprosy.

    Science.gov (United States)

    Baharuddin, Hazlyna; Taib, Tarita; Zain, Mollyza Mohd; Ch'ng, Shereen

    2016-10-01

    Leprosy is a chronic granulomatous infection caused by Mycobacterium leprae with predominant involvement of skin and nerves. We present a 70-year-old man with leprosy whose initial presentation resembled rheumatologic disease, due to leprae reaction. He presented with an 8-week history of worsening neuropathic pain in the right forearm, associated with necrotic skin lesions on his fingers that had ulcerated. Physical examination revealed two tender necrotic ulcers at the tip of the right middle finger and the dorsal aspect of the left middle finger. The patient had right wrist tenosynovitis and right elbow bursitis. Apart from raised inflammatory markers, the investigations for infection, connective tissue disease, vasculitis, thromboembolic disease and malignancy were negative. During the fourth week of hospitalization, we noticed a 2-cm hypoesthetic indurated plaque on the right inner arm. Further examination revealed thickened bilateral ulnar, radial and popliteal nerves. A slit skin smear was negative. Two skin biopsies and a biopsy of the olecranon bursa revealed granulomatous inflammation. He was diagnosed with paucibacillary leprosy with neuritis. He responded well to multidrug therapy and prednisolone; his symptoms resolved over a few weeks. This case illustrates the challenges in diagnosing a case of leprosy with atypical presentation in a non-endemic country. © 2016 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

  12. Role of Antioxidants and Natural Products in Inflammation

    Directory of Open Access Journals (Sweden)

    Palanisamy Arulselvan

    2016-01-01

    Full Text Available Inflammation is a comprehensive array of physiological response to a foreign organism, including human pathogens, dust particles, and viruses. Inflammations are mainly divided into acute and chronic inflammation depending on various inflammatory processes and cellular mechanisms. Recent investigations have clarified that inflammation is a major factor for the progression of various chronic diseases/disorders, including diabetes, cancer, cardiovascular diseases, eye disorders, arthritis, obesity, autoimmune diseases, and inflammatory bowel disease. Free radical productions from different biological and environmental sources are due to an imbalance of natural antioxidants which further leads to various inflammatory associated diseases. In this review article, we have outlined the inflammatory process and its cellular mechanisms involved in the progression of various chronic modern human diseases. In addition, we have discussed the role of free radicals-induced tissue damage, antioxidant defence, and molecular mechanisms in chronic inflammatory diseases/disorders. The systematic knowledge regarding the role of inflammation and its associated adverse effects can provide a clear understanding in the development of innovative therapeutic targets from natural sources that are intended for suppression of various chronic inflammations associated diseases.

  13. 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)

  14. 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

  15. 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.

  16. The crosstalk of gut microbiota and chronic kidney disease: role of inflammation, proteinuria, hypertension, and diabetes mellitus.

    Science.gov (United States)

    Kanbay, Mehmet; Onal, Emine M; Afsar, Baris; Dagel, Tuncay; Yerlikaya, Aslihan; Covic, Adrian; Vaziri, Nosratola D

    2018-05-04

    Chronic kidney disease (CKD) has been shown to result in profound changes in the composition and functions of the gut microbial flora which by disrupting intestinal epithelial barrier and generating toxic by-products contributes to systemic inflammation and the associated complications. On the other hand, emerging evidence points to the role of the gut microbiota in the development and progression of CKD by provoking inflammation, proteinuria, hypertension, and diabetes. These observations demonstrate the causal interconnection between the gut microbial dysbiosis and CKD. The gut microbiota closely interacts with the inflammatory, renal, cardiovascular, and endocrine systems via metabolic, humoral, and neural signaling pathways, events which can lead to chronic systemic inflammation, proteinuria, hypertension, diabetes, and kidney disease. Given the established role of the gut microbiota in the development and progression of CKD and its complications, favorable modification of the composition and function of the gut microbiome represents an appealing therapeutic target for prevention and treatment of CKD. This review provides an overview of the role of the gut microbial dysbiosis in the pathogenesis of the common causes of CKD including hypertension, diabetes, and proteinuria as well as progression of CKD.

  17. Hypothyroidism being caused by chronic autoimmune inflammation of the thyroid gland

    Directory of Open Access Journals (Sweden)

    Katarzyna Szwajkosz

    2017-04-01

    Full Text Available Disorders of the endocrine system are extremely important problems in Poland and around the world. According to the data presented by the Central Statistical Office in Poland in 2006, 22 % of the population suffered from thyroid disorders.  Hypothyroidism is usually caused by chronic autoimmune inflammation of the thyroid gland. It is one of the most common disorders of the thyroid concerning approximately 2% of the adult population. This disorder is related to higher risk of overweight and obesity due to decreased total body metabolism. Furthermore, it predisposes to dyslipidaemia thus increases the risk of cardiovascular disease.

  18. Odor Signals of Immune Activation and CNS Inflammation

    Science.gov (United States)

    2014-12-01

    inflammation results in detectable alteration of body odor and that traumatic brain injury (TBI) might similarly produce volatile metabolites specific to...Because both LPS and TBI elicit inflammatory processes and LPS-induced inflammation induces body odor changes, we hypothesized that (1) TBI would...induce a distinct change in body odor and (2) this change would resemble the change induced by LPS. Mice receiving surgery and lateral fluid percussion

  19. 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.

  20. Comprehensive Genetic Characterization of Intraprostatic Chronic Inflammation and Prostate Cancer in African American Men

    Science.gov (United States)

    2017-09-01

    Response and Eradication of Androgen Receptor Amplification with High-dose Testosterone in Prostate Cancer ." Eur Urol 71(6): 997-998. Case Report...34 Prostate -specific Antigen Response and Eradication of Androgen Receptor Amplification with High-dose Testosterone in Prostate Cancer ." Eur Urol 71...AWARD NUMBER: W81XWH-15-1-0379 TITLE: Comprehensive genetic characterization of intraprostatic chronic inflammation and prostate cancer in

  1. 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) bro...

  2. Obesity and Inflammation: Epidemiology, Risk Factors, and Markers of Inflammation

    Directory of Open Access Journals (Sweden)

    Heriberto Rodríguez-Hernández

    2013-01-01

    Full Text Available Obesity is a public health problem that has reached epidemic proportions with an increasing worldwide prevalence. The global emergence of obesity increases the risk of developing chronic metabolic disorders. Thus, it is an economic issue that increased the costs of the comorbidities associated. Moreover, in recent years, it has been demonstrated that obesity is associated with chronic systemic inflammation, this status is conditioned by the innate immune system activation in adipose tissue that promotes an increase in the production and release of pro-inflammatory cytokines that contribute to the triggering of the systemic acute-phase response which is characterized by elevation of acute-phase protein levels. On this regard, low-grade chronic inflammation is a characteristic of various chronic diseases such as metabolic syndrome, cardiovascular disease, diabetes, hypertension, non-alcoholic fatty liver disease, and some cancers, among others, which are also characterized by obesity condition. Thus, a growing body of evidence supports the important role that is played by the inflammatory response in obesity condition and the pathogenesis of chronic diseases related.

  3. Dietary Anthocyanins against Obesity and Inflammation.

    Science.gov (United States)

    Lee, Yoon-Mi; Yoon, Young; Yoon, Haelim; Park, Hyun-Min; Song, Sooji; Yeum, Kyung-Jin

    2017-10-01

    Chronic low-grade inflammation plays a pivotal role in the pathogenesis of obesity, due to its associated chronic diseases such as type II diabetes, cardiovascular diseases, pulmonary diseases and cancer. Thus, targeting inflammation is an attractive strategy to counter the burden of obesity-induced health problems. Recently, food-derived bioactive compounds have been spotlighted as a regulator against various chronic diseases due to their low toxicity, as opposed to drugs that induce severe side effects. Here we describe the beneficial effects of dietary anthocyanins on obesity-induced metabolic disorders and inflammation. Red cabbage microgreen, blueberry, blackcurrant, mulberry, cherry, black elderberry, black soybean, chokeberry and jaboticaba peel contain a variety of anthocyanins including cyanidins, delphinidins, malvidins, pelargonidins, peonidins and petunidins, and have been reported to alter both metabolic markers and inflammatory markers in cells, animals, and humans. This review discusses the interplay between inflammation and obesity, and their subsequent regulation via the use of dietary anthocyanins, suggesting an alternative dietary strategy to ameliorate obesity and obesity associated chronic diseases.

  4. PET-scan shows peripherally increased neurokinin 1 receptor availability in chronic tennis elbow: visualizing neurogenic inflammation?

    Directory of Open Access Journals (Sweden)

    Magnus Peterson

    Full Text Available In response to pain, neurokinin 1 (NK1 receptor availability is altered in the central nervous system. The NK1 receptor and its primary agonist, substance P, also play a crucial role in peripheral tissue in response to pain, as part of neurogenic inflammation. However, little is known about alterations in NK1 receptor availability in peripheral tissue in chronic pain conditions and very few studies have been performed on human beings. Ten subjects with chronic tennis elbow were therefore examined by positron emission tomography (PET with the NK1 specific radioligand [(11C]GR205171 before and after treatment with graded exercise. The radioligand signal intensity was higher in the affected arm as compared with the unaffected arm, measured as differences between the arms in volume of voxels and signal intensity of this volume above a reference threshold set as 2.5 SD above mean signal intensity of the unaffected arm before treatment. In the eight subjects examined after treatment, pain ratings decreased in all subjects but signal intensity decreased in five and increased in three. In conclusion, NK1 receptors may be activated, or up-regulated in the peripheral, painful tissue of a chronic pain condition. This up-regulation does, however, have moderate correlation to pain ratings. The increased NK1 receptor availability is interpreted as part of ongoing neurogenic inflammation and may have correlation to the pathogenesis of chronic tennis elbow.ClinicalTrials.gov NCT00888225 http://clinicaltrials.gov/

  5. 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.

  6. 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

  7. Does facial resemblance enhance cooperation?

    Directory of Open Access Journals (Sweden)

    Trang Giang

    Full Text Available Facial self-resemblance has been proposed to serve as a kinship cue that facilitates cooperation between kin. In the present study, facial resemblance was manipulated by morphing stimulus faces with the participants' own faces or control faces (resulting in self-resemblant or other-resemblant composite faces. A norming study showed that the perceived degree of kinship was higher for the participants and the self-resemblant composite faces than for actual first-degree relatives. Effects of facial self-resemblance on trust and cooperation were tested in a paradigm that has proven to be sensitive to facial trustworthiness, facial likability, and facial expression. First, participants played a cooperation game in which the composite faces were shown. Then, likability ratings were assessed. In a source memory test, participants were required to identify old and new faces, and were asked to remember whether the faces belonged to cooperators or cheaters in the cooperation game. Old-new recognition was enhanced for self-resemblant faces in comparison to other-resemblant faces. However, facial self-resemblance had no effects on the degree of cooperation in the cooperation game, on the emotional evaluation of the faces as reflected in the likability judgments, and on the expectation that a face belonged to a cooperator rather than to a cheater. Therefore, the present results are clearly inconsistent with the assumption of an evolved kin recognition module built into the human face recognition system.

  8. Pseudomonas aeruginosa biofilm aggravates skin inflammatory response in BALB/c mice in a novel chronic wound model

    DEFF Research Database (Denmark)

    Trøstrup, Hannah; Thomsen, Kim; Christophersen, Lars J

    2013-01-01

    model in C3H/HeN and BALB/c mice. The chronic wound was established by an injection of seaweed alginate-embedded P. aeruginosa PAO1 beneath a third-degree thermal lesion providing full thickness skin necrosis, as in human chronic wounds. Cultures revealed growth of PA, and both alginate with or without......Chronic wounds are presumed to persist in the inflammatory state, preventing healing. Emerging evidence indicates a clinical impact of bacterial biofilms in soft tissues, including Pseudomonas aeruginosa (PA) biofilms. To further investigate this, we developed a chronic PA biofilm wound infection...... bacteria organized in clusters, resembling biofilms, and inflammation located adjacent to the PA. The chronic wound infection showed a higher number of PAO1 in the BALB/c mice at day 4 after infection as compared to C3H/HeN mice (p

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  10. The Complex Interplay between Chronic Inflammation, the Microbiome, and Cancer: Understanding Disease Progression and What We Can Do to Prevent It

    Directory of Open Access Journals (Sweden)

    Heather Armstrong

    2018-03-01

    Full Text Available Cancer is a multifaceted condition, in which a senescent cell begins dividing in an irregular manner due to various factors such as DNA damage, growth factors and inflammation. Inflammation is not typically discussed as carcinogenic; however, a significant percentage of cancers arise from chronic microbial infections and damage brought on by chronic inflammation. A hallmark cancer-inducing microbe is Helicobacter pylori and its causation of peptic ulcers and potentially gastric cancer. This review discusses the recent developments in understanding microbes in health and disease and their potential role in the progression of cancer. To date, microbes can be linked to almost every cancer, including colon, pancreatic, gastric, and even prostate. We discuss the known mechanisms by which these microbes can induce cancer growth and development and how inflammatory cells may contribute to cancer progression. We also discuss new treatments that target the chronic inflammatory conditions and their associated cancers, and the impact microbes have on treatment success. Finally, we examine common dietary misconceptions in relation to microbes and cancer and how to avoid getting caught up in the misinterpretation and over inflation of the results.

  11. Cumulative childhood risk is associated with a new measure of chronic inflammation in adulthood

    DEFF Research Database (Denmark)

    Rasmussen, Line Jee Hartmann; Moffitt, Terrie E; Eugen-Olsen, Jesper

    2018-01-01

    BACKGROUND: Childhood risk factors are associated with elevated inflammatory biomarkers in adulthood, but it is unknown whether these risk factors are associated with increased adult levels of the chronic inflammation marker soluble urokinase plasminogen activator receptor (suPAR). We aimed to test...... the hypothesis that childhood exposure to risk factors for adult disease is associated with elevated suPAR in adulthood and to compare suPAR with the oft-reported inflammatory biomarker C-reactive protein (CRP). METHODS: Prospective study of a population-representative 1972-1973 birth cohort; the Dunedin...... Multidisciplinary Health and Development Study observed participants to age 38 years. Main childhood predictors were poor health, socioeconomic disadvantage, adverse childhood experiences (ACEs), low IQ, and poor self-control. Main adult outcomes were adulthood inflammation measured as suPAR and high...

  12. Expression of Heat Shock Protein 27 in Benign Prostatic Hyperplasia with Chronic Inflammation

    OpenAIRE

    Jiang, Yuqing; Wang, Xiuli; Guo, Yuexian; Li, Wenping; Yang, Shijie; Li, Wei; Cai, Wenqing

    2015-01-01

    Background Heat shock protein 27 (HSP 27) is known as a mediator in immune response and has been recently found to be expressed in prostate cancer. This study aimed to investigate the role of HSP27 in inflammatory BPH. Material/Methods Hospitalized BPH patients who received TURP were divided into 4 groups by the presence and degrees of chronic inflammation: non-inflammatory BPH (NI BPH), mild-inflammatory BPH (MI BPH), moderate-inflammatory BPH (MOI BPH), and severe-inflammatory BPH (SI BPH)....

  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. 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 ...

  15. 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.

  16. 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.

  17. Inflammation and Oxidative Stress in Obesity-Related Glomerulopathy

    OpenAIRE

    Tang, Jinhua; Yan, Haidong; Zhuang, Shougang

    2012-01-01

    Obesity-related glomerulopathy is an increasing cause of end-stage renal disease. Obesity has been considered a state of chronic low-grade systemic inflammation and chronic oxidative stress. Augmented inflammation in adipose and kidney tissues promotes the progression of kidney damage in obesity. Adipose tissue, which is accumulated in obesity, is a key endocrine organ that produces multiple biologically active molecules, including leptin, adiponectin, resistin, that affect inflammation, and ...

  18. The combination of Bifidobacterium breve with non-digestible oligosaccharides suppresses airway inflammation in a murine model for chronic asthma.

    Science.gov (United States)

    Sagar, Seil; Vos, Arjan P; Morgan, Mary E; Garssen, Johan; Georgiou, Niki A; Boon, Louis; Kraneveld, Aletta D; Folkerts, Gert

    2014-04-01

    Over the last decade, there has been a growing interest in the use of interventions that target the intestinal microbiota as a treatment approach for asthma. This study is aimed at exploring the therapeutic effects of long-term treatment with a combination of Bifidobacterium breve with non-digestible oligosaccharides on airway inflammation and remodeling. A murine ovalbumin-induced chronic asthma model was used. Pulmonary airway inflammation; mRNA expression of pattern recognition receptors, Th-specific cytokines and transcription factors in lung tissue; expression of Foxp3 in blood Th cells; in vitro T cell activation; mast cell degranulation; and airway remodeling were examined. The combination of B. breve with non-digestible oligosaccharides suppressed pulmonary airway inflammation; reduced T cell activation and mast cell degranulation; modulated expression of pattern recognition receptors, cytokines and transcription factors; and reduced airway remodeling. The treatment induced regulatory T cell responses, as shown by increased Il10 and Foxp3 transcription in lung tissue, and augmented Foxp3 protein expression in blood CD4+CD25+Foxp3+ T cells. This specific combination of beneficial bacteria with non-digestible oligosaccharides has strong anti-inflammatory properties, possibly via the induction of a regulatory T cell response, resulting in reduced airway remodeling and, therefore, may be beneficial in the treatment of chronic inflammation in allergic asthma. Copyright © 2014 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    Majewski, Sebastian; Pietrzak, Anna; Tworek, Damian; Szewczyk, Karolina; Kumor-Kisielewska, Anna; Kurmanowska, Zofia; Górski, Paweł; Zalewska-Janowska, Anna; Piotrowski, Wojciech Jerzy

    2017-01-01

    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. 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. There were significant differences between COPD patients and healthy never-smokers in skin temperature, melanin index, sebum content, and hydration level ( P skin measured. The mean levels of hsCRP and IL-6 in serum were significantly higher in COPD patients and healthy smokers in comparison with healthy never-smokers. There were significant correlations between skin temperature and serum hsCRP ( R =0.40; P =0.02) as well as skin temperature and serum IL-6 ( R =0.49; P =0.005) in smokers. Stratum corneum hydration correlated significantly with serum TNF-α ( R =0.37; P =0.01) in COPD patients. Differences noted in several skin biophysical properties and biomarkers of systemic inflammation between COPD patients, smokers, and healthy never-smokers may suggest a possible link between smoking-driven, low-grade systemic inflammation, and the overall skin condition.

  20. Chronic graft-versus-host disease in the rat radiation chimera: I. clinical features, hematology, histology, and immunopathology in long-term chimeras

    Energy Technology Data Exchange (ETDEWEB)

    Beschorner, W.E.; Tutschka, P.J.; Santos, G.W.

    1982-04-01

    The clinical features, pathology, and immunopathology of chronic graft-versus-host disease (GVHD) developing in the long-term rat radiation chimera are described. At 6 to 12 months post-transplant, the previously stable ACI/LEW chimeras developed patchy to diffuse severe hair loss and thickened skin folds, and had microscopic features resembling scleroderma, Sjogren's syndrome, and chronic hepatitis. Skin histology showed dermal inflammation and acanthosis with atrophy of the appendages, with progression to dermal sclerosis. The liver revealed chronic hepatitis with bile duct injury and proliferation and periportal piecemeal necrosis. The tongue had considerable submucosal inflammation, muscular necrosis, and atrophy and arteritis. The serous salivary glands, lacrimal glands, and bronchi had lymphocytic inflammation and injury to duct, acinar, and mucosal columnar epithelium. The thymus had lymphocyte depletion of the medulla with prominent epithelium. The spleen and lymph nodes had poorly developed germinal centers but increased numbers of plasma cells. IgM was observed along the basement membrane and around the basal cells of the skin and tongue and along the basement membrane of the bile ducts. IgM was present also in the arteries of the tongue. Immunoglobulins eluted from the skin, cross-reacted with the bile duct epithelium and usually with both ACI and Lewis skin. Increased titers of speckled antinuclear antibodies were present in the serum of rats with chronic (GVHD). Chronic GVHD in the long-term rat radiation chimera is very similar to human chronic GVHD and is a potentially excellent model for autoimmune disorders including scleroderma, Sjorgren's syndrome, and chronic hepatitis.

  1. Chronic graft-versus-host disease in the rat radiation chimera: I. clinical features, hematology, histology, and immunopathology in long-term chimeras

    International Nuclear Information System (INIS)

    Beschorner, W.E.; Tutschka, P.J.; Santos, G.W.

    1982-01-01

    The clinical features, pathology, and immunopathology of chronic graft-versus-host disease (GVHD) developing in the long-term rat radiation chimera are described. At 6 to 12 months post-transplant, the previously stable ACI/LEW chimeras developed patchy to diffuse severe hair loss and thickened skin folds, and had microscopic features resembling scleroderma, Sjogren's syndrome, and chronic hepatitis. Skin histology showed dermal inflammation and acanthosis with atrophy of the appendages, with progression to dermal sclerosis. The liver revealed chronic hepatitis with bile duct injury and proliferation and periportal piecemeal necrosis. The tongue had considerable submucosal inflammation, muscular necrosis, and atrophy and arteritis. The serous salivary glands, lacrimal glands, and bronchi had lymphocytic inflammation and injury to duct, acinar, and mucosal columnar epithelium. The thymus had lymphocyte depletion of the medulla with prominent epithelium. The spleen and lymph nodes had poorly developed germinal centers but increased numbers of plasma cells. IgM was observed along the basement membrane and around the basal cells of the skin and tongue and along the basement membrane of the bile ducts. IgM was present also in the arteries of the tongue. Immunoglobulins eluted from the skin, cross-reacted with the bile duct epithelium and usually with both ACI and Lewis skin. Increased titers of speckled antinuclear antibodies were present in the serum of rats with chronic (GVHD). Chronic GVHD in the long-term rat radiation chimera is very similar to human chronic GVHD and is a potentially excellent model for autoimmune disorders including scleroderma, Sjorgren's syndrome, and chronic hepatitis

  2. Ginseng treatment reduces bacterial load and lung pathology in chronic Pseudomonas aeruginosa pneumonia in rats

    DEFF Research Database (Denmark)

    Song, Z; Johansen, H K; Faber, V

    1997-01-01

    the inflammation and antibody responses could be changed by treatment with the Chinese herbal medicine ginseng. An aqueous extract of ginseng was injected subcutaneously, and cortisone and saline were used as controls. Two weeks after challenge with P. aeruginosa, the ginseng-treated group showed a significantly...... resembling a TH1-like response. On the basis of these results it is suggested that ginseng may have the potential to be a promising natural medicine, in conjunction with other forms of treatment, for CF patients with chronic P. aeruginosa lung infection....

  3. Malnutrition and chronic inflammation as risk factors for sarcopenia in elderly patients with hip fracture.

    Science.gov (United States)

    Yoo, Jun-Il; Ha, Yong-Chan; Choi, Hana; Kim, Kyu-Hwang; Lee, Young-Kyun; Koo, Kyung-Hoi; Park, Ki-Soo

    2018-01-01

    To evaluate malnutrition and chronic inflammation as risk factors for sarcopenia in elderly patients with hip fractures, as defined by the criteria of the Asian Working Group on Sarcopenia (AWGS). A total of 327 elderly patients with hip fractures were enrolled in this retrospective observational study. The main outcome measure was the nutritional status and nutritional risk factors for sarcopenia in elderly patients. Diagnosis of sarcopenia was made according to the guidelines of the AWGS. Whole body densitometry analysis was used to measure skeletal muscle mass, and muscle strength was evaluated by handgrip testing. Multivariable regression analysis was utilized to analyze the nutritional risk factors for sarcopenia in patients with hip fractures. Of 327 patients with hip fractures (78 men and 249 women), the prevalence of sarcopenia was 60.3% and 30.1% in men and women, respectively. The rates of three indicators of malnutrition in men and women (low BMI, hypoalbuminemia, and hypoproteinemia) in sarcopenia patients with hip fractures were 23.4%, 31.9%, and 53.2% and 21.3%, 21.3%, and 37.3%, respectively. The prevalence of markers of chronic inflammation (increased CRP and ESR) in men and women with sarcopenia and hip fractures were 74.9% and 52.2%, and 49.3% and 85.1%, respectively. After adjusting for covariates, low BMI and hypoproteinemia in women were associated with a 2.9- and 2.1-fold greater risk of sarcopenia than non-sarcopenia, respectively. The present study revealed a strong relationship between sarcopenia and malnutrition and chronic inflammatory factors in elderly patients with hip fractures.

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

    Science.gov (United States)

    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.

  5. Adipose Tissue Inflammation Induces B Cell Inflammation and Decreases B Cell Function in Aging

    Directory of Open Access Journals (Sweden)

    Daniela Frasca

    2017-08-01

    Full Text Available Aging is the greatest risk factor for developing chronic diseases. Inflamm-aging, the age-related increase in low-grade chronic inflammation, may be a common link in age-related diseases. This review summarizes recent published data on potential cellular and molecular mechanisms of the age-related increase in inflammation, and how these contribute to decreased humoral immune responses in aged mice and humans. Briefly, we cover how aging and related inflammation decrease antibody responses in mice and humans, and how obesity contributes to the mechanisms for aging through increased inflammation. We also report data in the literature showing adipose tissue infiltration with immune cells and how these cells are recruited and contribute to local and systemic inflammation. We show that several types of immune cells infiltrate the adipose tissue and these include macrophages, neutrophils, NK cells, innate lymphoid cells, eosinophils, T cells, B1, and B2 cells. Our main focus is how the adipose tissue affects immune responses, in particular B cell responses and antibody production. The role of leptin in generating inflammation and decreased B cell responses is also discussed. We report data published by us and by other groups showing that the adipose tissue generates pro-inflammatory B cell subsets which induce pro-inflammatory T cells, promote insulin resistance, and secrete pathogenic autoimmune antibodies.

  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.

    Science.gov (United States)

    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. 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.

  8. 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

  9. Indicators of inflammation and cellular damage in chronic asymptomatic or oligosymptomatic alcoholics: correlation with alteration of bilirubin and hepatic and pancreatic enzymes

    OpenAIRE

    Borini, Paulo; Guimarães, Romeu Cardoso

    1999-01-01

    Biochemical and hematimetric indicators of inflammation and cell damage were correlated with bilirubin and hepatic and pancreatic enzymes in 30 chronic male alcoholics admitted into psychiatric hospital for detoxification and treatment of alcoholism. Aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, alkaline phosphatase, and total bilirubin were altered, respectively, in 90%, 63%, 87%, 23% and 23% of the cases. None of the indicators of inflammation (lactic dehy...

  10. Role of hepcidin-ferroportin axis in the pathophysiology, diagnosis, and treatment of anemia of chronic inflammation.

    Science.gov (United States)

    Langer, Arielle L; Ginzburg, Yelena Z

    2017-06-01

    Anemia of chronic inflammation (ACI) is a frequently diagnosed anemia and portends an independently increased morbidity and poor outcome associated with multiple underlying diseases. The pathophysiology of ACI is multifactorial, resulting from the effects of inflammatory cytokines which both directly and indirectly suppress erythropoiesis. Recent advances in molecular understanding of iron metabolism provide strong evidence that immune mediators, such as IL-6, lead to hepcidin-induced hypoferremia, iron sequestration, and decreased iron availability for erythropoiesis. The role of hepcidin-ferroportin axis in the pathophysiology of ACI is stimulating the development of new diagnostics and targeted therapies. In this review, we present an overview of and rationale for inflammation-, iron-, and erythropoiesis-related strategies currently in development. © 2017 International Society for Hemodialysis.

  11. 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

  12. Suppression of Th17-polarized airway inflammation by rapamycin.

    Science.gov (United States)

    Joean, Oana; Hueber, Anja; Feller, Felix; Jirmo, Adan Chari; Lochner, Matthias; Dittrich, Anna-Maria; Albrecht, Melanie

    2017-11-10

    Because Th17-polarized airway inflammation correlates with poor control in bronchial asthma and is a feature of numerous other difficult-to-treat inflammatory lung diseases, new therapeutic approaches for this type of airway inflammation are necessary. We assessed different licensed anti-inflammatory agents with known or expected efficacy against Th17-polarization in mouse models of Th17-dependent airway inflammation. Upon intravenous transfer of in vitro derived Th17 cells and intranasal challenge with the corresponding antigen, we established acute and chronic murine models of Th17-polarised airway inflammation. Consecutively, we assessed the efficacy of methylprednisolone, roflumilast, azithromycin, AM80 and rapamycin against acute or chronic Th17-dependent airway inflammation. Quantifiers for Th17-associated inflammation comprised: bronchoalveolar lavage (BAL) differential cell counts, allergen-specific cytokine and immunoglobulin secretion, as well as flow cytometric phenotyping of pulmonary inflammatory cells. Only rapamycin proved effective against acute Th17-dependent airway inflammation, accompanied by increased plasmacytoid dendritic cells (pDCs) and reduced neutrophils as well as reduced CXCL-1 levels in BAL. Chronic Th17-dependent airway inflammation was unaltered by rapamycin treatment. None of the other agents showed efficacy in our models. Our results demonstrate that Th17-dependent airway inflammation is difficult to treat with known agents. However, we identify rapamycin as an agent with inhibitory potential against acute Th17-polarized airway inflammation.

  13. 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

  14. 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.

  15. Balance impairment and systemic inflammation in chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Tudorache E

    2015-09-01

    Full Text Available Emanuela Tudorache,1 Cristian Oancea,1 Claudiu Avram,2 Ovidiu Fira-Mladinescu,1 Lucian Petrescu,3 Bogdan Timar4 1Department of Pulmonology, University of Medicine and Pharmacy “Victor Babes”, 2Physical Education and Sport Faculty, West University of Timisoara, 3Department of Cardiology, University of Medicine and Pharmacy “Victor Babes”, 4Department of Biostatistics and Medical Informatics, University of Medicine and Pharmacy “Victor Babes”, Timisoara, Romania Background/purpose: Chronic obstructive pulmonary disease (COPD, especially in severe forms, is commonly associated with systemic inflammation and balance impairment. The aim of our study was to evaluate the impact on equilibrium of stable and exacerbation (acute exacerbation of COPD [AECOPD] phases of COPD and to investigate if there is a connection between lower extremity muscle weakness and systemic inflammation.Methods: We enrolled 41 patients with COPD (22 stable and 19 in AECOPD and 20 healthy subjects (control group, having no significant differences regarding the anthropometric data. We analyzed the differences in balance tests scores: Falls Efficacy Scale-International (FES-I questionnaire, Berg Balance Scale (BBS, Timed Up and Go (TUG test, Single Leg Stance (SLS, 6-minute walking distance (6MWD, isometric knee extension (IKE between these groups, and also the correlation between these scores and inflammatory biomarkers.Results: The presence and severity of COPD was associated with significantly decreased score in IKE (P<0.001, 6MWD (P<0.001, SLS (P<0.001, and BBS (P<0.001, at the same time noting a significant increase in median TUG score across the studied groups (P<0.001. The AECOPD group vs stable group presented a significant increase in high-sensitive C-reactive protein (hs-CRP levels (10.60 vs 4.01; P=0.003 and decrease in PaO2 (70.1 vs 59.1; P<0.001. We observed that both IKE scores were significantly and positive correlated with all the respiratory volumes

  16. 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,

  17. Intestinal inflammation in TNBS sensitized rats as a model of chronic inflammatory bowel disease

    Directory of Open Access Journals (Sweden)

    N. Selve

    1992-01-01

    Full Text Available An enteritis, based on a delayed-type hypersensitivity reaction, was induced in TNBS (2,4,4-trinitrobenzenesulphonic acid sensitized rats by multiple intrajejunal challenge with TNBS via an implanted catheter. This treatment induced chronic inflammation of the distal small intestine characterized by intense hyperaemia, oedema and gut wall thickening as assessed by macroscopic scoring and weighing a defined part of the dissected intestine. Histologically, the inflammatory response included mucosal and submucosal cell infiltration by lymphocytes and histiocytes, transmural granulomatous inflammation with multinucleated cells and activated mesenteric lymph nodes. Ex vivo stimulated release of the inflammatory mediator LTB4 in the dissected part of the intestine was increased following TNBS treatment. Drug treatment with sulphasalazine or 5-aminosalicylic acid improved the enteritis score and attenuated TNBS induced oedema formation and LTB4 production. The applicability and relevance of this new model are discussed with respect to drug development and basic research of inflammatory bowel diseases.

  18. Impact of daily cooling treatment on skin inflammation in patients with chronic venous disease.

    Science.gov (United States)

    Kelechi, Teresa J; Mueller, Martina; King, Dana E; Madisetti, Mohan; Prentice, Margie

    2015-05-01

    People with chronic venous disease are at high risk for developing venous leg ulcers. Inflammation is posited as a pathological factor for this chronic condition as evidenced by persistently elevated skin temperature. As part of a larger trial to test the effects of a cooling regimen on leg ulcer prevention, the objective of this preliminary study was to evaluate the first 30 days of intense daily cooling. Compared to a placebo control cuff, a gel cuff applied to the most severely affected lower leg skin for 30 min daily showed no statistically significant differences between temperatures taken in the home at baseline compared to those measured at the 1 month follow up visit. There were also no differences in temperatures noted between the two groups, although the temperatures in the treatment group were lower 30 min after treatment, an indication of adherence. There was no discernable decrease or increase in temperature at a given time point during the 30 day treatment period compared to the control group. It may be better to have patients monitor skin temperature on a daily basis and then apply the cuff as necessary, rather than requiring daily cooling based on baseline measurement. This "prn" approach may provide a sufficient cooling milieu to prevent escalation of inflammation and thwart ulcer occurrence or recurrence. Clinical trials registration #NCT01509599. Copyright © 2015 Tissue Viability Society. Published by Elsevier Ltd. All rights reserved.

  19. The Interplay between Inflammation and Fibrosis in Kidney Transplantation

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    Irina B. Torres

    2014-01-01

    Full Text Available Serial surveillance renal allograft biopsies have shown that early subclinical inflammation constitutes a risk factor for the development of interstitial fibrosis. More recently, it has been observed that persistent inflammation is also associated with fibrosis progression and chronic humoral rejection, two histological conditions associated with poor allograft survival. Treatment of subclinical inflammation with steroid boluses prevents progression of fibrosis and preserves renal function in patients treated with a cyclosporine-based regimen. Subclinical inflammation has been reduced after the introduction of tacrolimus based regimens, and it has been shown that immunosuppressive schedules that are effective in preventing acute rejection and subclinical inflammation may prevent the progression of fibrosis and chronic humoral rejection. On the other hand, minimization protocols are associated with progression of fibrosis, and noncompliance with the immunosuppressive regime constitutes a major risk factor for chronic humoral rejection. Thus, adequate immunosuppressive treatment, avoiding minimization strategies and reinforcing educational actions to prevent noncompliance, is at present an effective approach to combat the progression of fibrosis.

  20. The role of serratiopeptidase in the resolution of inflammation

    Directory of Open Access Journals (Sweden)

    Manju Tiwari

    2017-05-01

    Full Text Available Inflammation remains a key event during most of the diseases and physiological imbalance. Acute inflammation is an essential physiological event by immune system for a protective measure to remove cause of inflammation and failure of resolution lead to chronic inflammation. Over a period of time, a number of drugs mostly chemical have been deployed to combat acute and chronic inflammation. Recently, enzyme based anti-inflammatory drugs became popular over conventional chemical based drugs. Serratiopeptidase, a proteolytic enzyme from trypsin family, possesses tremendous scope in combating inflammation. Serine protease possesses a higher affinity for cyclooxygenase (COX-I and COX-II, a key enzyme associated with production of different inflammatory mediators including interleukins (IL, prostaglandins (PGs and thromboxane (TXs etc. Currently, arthritis, sinusitis, bronchitis, fibrocystic breast disease, and carpal tunnel syndrome, etc. are the leading inflammatory disorders that affected the entire the globe. In order to conquer inflammation, both acute and chronic world, physician mostly relies on conventional drugs. The most common drugs to combat acute inflammation are Nonsteroidal anti-inflammatory drugs (NSAIDs alone and or in combination with other drugs. However, during chronic inflammation, NSAIDs are often used with steroidal drugs such as autoimmune disorders. These drugs possess several limitations such as side effects, ADR, etc. In order to overcome these limitations and complications, enzyme based drugs (anti-inflammatory emerged, and aim for a new high since the last decade. Serine protease, the largest proteolytic family has been reported for several therapeutic applications, including anti-inflammatory. Serratiopeptidase is a leading enzyme which has a very long history in medical as an effective anti-inflammatory drug. Current study emphasizes present scenario and future prospect of serratiopeptidase as an anti-inflammatory drug

  1. [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.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. 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.

  4. The intriguing role of Rifaximin in gut barrier chronic inflammation and in the treatment of Crohn's disease.

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    Lopetuso, Loris R; Napoli, Marco; Rizzatti, Gianenrico; Gasbarrini, Antonio

    2018-06-04

    The gastrointestinal tract acts as a functional unit organized as a semipermeable multilayer system, in which commensal gut microbiota represents the anatomical barrier. Recently,, several studies have highlighted the involvement of gut microbiota in IBD pathogenesis, in sustaining gut barrier chronic inflammation, and in conditioning disease course and therapeutical response. This evidence provides a rationale for treating patients with gut microbiota modifiers. Among these, Rifaximin represents a non-traditional antibiotic able to act as a "eubiotic" on intestinal barrier. Area covered: The purpose of this narrative review is to explore the impact of Rifaximin on gut barrier and gut microbiota in IBD, in particular in Crohn's disease, and to analyze its potential therapeutic applications. Expert opinion: The possibility of a beneficial activity of Rifaximin in chronic intestinal inflammation and Crohn's disease has been debated and evaluated with different studies having obtained promising but still preliminary data. Larger trials are therefore needed. This gut-specific antibiotic could represent an alternative to systemic antibiotics thanks to its favorable safety profile and promising efficacy data. Rifaximin could exert, when appropriate, a synergic effect with immunomodulators in IBD, acting on both the microbial and immunological sides of gut barrier impairment.

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

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    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.

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

    Science.gov (United States)

    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.

  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. 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

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

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    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

  10. Features of blood serum protein spectrum and cytokine spectrum of rats with chronic carrageenan-induced intestinal inflammation

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    A. S. Tkachenko

    2014-04-01

    Full Text Available It has been established that features of modern diet might be considered as a possible source of inflammatory diseases of gastrointestinal tract. Particular attention is paid to the role of different food additives in the development of intestinal inflammation, including the food additive E407, known as carrageenan. A model of chronic carrageenan-induced gastroenterocolitis of moderate severity has been elaborated, which allows us to study carrageenan-induced intestinal inflammation. In particular, the features of blood serum protein spectrum and cytokine spectrum in chronic carrageenan-induced intestinal inflammation are not studied. The female Wistar rats have been used for the experiment. Chronic carrageenan-induced gastroenterocolitis has been reproduced by the free access of animals to 1% solution of carrageenan in drinking water. Laboratory animals have been divided into 3 groups. Group № 1 consisted of experimental animals, who consumed food additive carrageenan during 2 weeks and group № 2 included experimental animals, who consumed food additive carrageenan during 4 weeks. Group № 3 consisted of intact healthy animals. The development of gastroenterocolitis has been proved morphologically and biochemically. Manipulations with animals have been carried out in accordance with the provisions of the European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes (Strasbourg, 1986. It has been established that the disease has been associated with dysproteinemia. The level of α1-globulins increased after 2 weeks of carrageenan consumption and has been normalized in animals, who consumed carrageenan during 4 weeks. The similar changes have been observed for α2-globulins level. It could be explained by production of acute phase proteins, such as α1-acid glycoprotein, C-reactive protein, fibrinogen, α2-macroglobulin, ceruloplasmin, etc. The intake of carrageenan also caused

  11. Chronic inflammation triggered by the NLRP3 inflammasome in myeloid cells promotes growth plate dysplasia by mesenchymal cells.

    Science.gov (United States)

    Wang, Chun; Xu, Can-Xin; Alippe, Yael; Qu, Chao; Xiao, Jianqiu; Schipani, Ernestina; Civitelli, Roberto; Abu-Amer, Yousef; Mbalaviele, Gabriel

    2017-07-07

    Skeletal complications are common features of neonatal-onset multisystem inflammatory disease (NOMID), a disorder caused by NLRP3-activating mutations. NOMID mice in which NLRP3 is activated globally exhibit several characteristics of the human disease, including systemic inflammation and cartilage dysplasia, but the mechanisms of skeletal manifestations remain unknown. In this study, we find that activation of NLRP3 in myeloid cells, but not mesenchymal cells triggers chronic inflammation, which ultimately, causes growth plate and epiphyseal dysplasia in mice. These responses are IL-1 signaling-dependent, but independent of PARP1, which also functions downstream of NLRP3 and regulates skeletal homeostasis. Mechanistically, inflammation causes severe anemia and hypoxia in the bone environment, yet down-regulates the HIF-1α pathway in chondrocytes, thereby promoting the demise of these cells. Thus, activation of NLRP3 in hematopoietic cells initiates IL-1β-driven paracrine cascades, which promote abnormal growth plate development in NOMID mice.

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

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    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

  13. Inflammation versus Host Defense in Obesity

    OpenAIRE

    Wu, Huaizhu; Ballantyne, Christie M.

    2014-01-01

    Obesity is characterized by a state of low-grade, chronic inflammation. Wang et al. (2014) report that immune cells from obese mice have decreased production of IL-22, a cytokine involved in immune responses and inflammation, and reveal therapeutic effects of exogenous IL-22 against obesity-linked metabolic dysfunctions.

  14. Elevated [11C]-D-Deprenyl Uptake in Chronic Whiplash Associated Disorder Suggests Persistent Musculoskeletal Inflammation

    Science.gov (United States)

    Linnman, Clas; Appel, Lieuwe; Fredrikson, Mats; Gordh, Torsten; Söderlund, Anne; Långström, Bengt; Engler, Henry

    2011-01-01

    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. PMID:21541010

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

    Directory of Open Access Journals (Sweden)

    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.

  16. 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.

  17. Resemblance and investment in children.

    Science.gov (United States)

    Dolinska, Barbara

    2013-01-01

    According to evolutionary explanations men hardly ever are absolutely certain about their biological fatherhood therefore they must seek various sources of information to subjectively establish whether they are the genetic fathers of the children they raise. Apicella and Marlowe (2004) showed that fathers who perceived greater similarity between their children and themselves were willing to invest more resources (e.g., time, money, care) in their offspring presumably because the perceived resemblance indicated to the fathers their genetic relatedness with their children. The present study extended the design of Apicella and Marlowe's original study and included both fathers and mothers as participants. Parents were recruited by a female confederate at the airport and at the railway station in Wroclaw (Poland). Multiple regression analyses showed that perceived resemblance predicted parental investment in the child for both men and women. The fact that mothers' declarations of investment in their children also depended on the perceived resemblance factor is not consistent with evolutionary formulations delineated by Apicella and Marlowe (2004; 2007). Future studies must resolve the issue of whether the resemblance-investment relation in fathers results from men relaying on child's resemblance to themselves as an indicator of their own biological paternity, or whether it results from the more parsimonious phenomenon that people in general are attracted more to other people who are similar to them.

  18. Low-grade chronic inflammation perpetuated by modern diet as a promoter of obesity and osteoporosis.

    Science.gov (United States)

    Ilich, Jasminka Z; Kelly, Owen J; Kim, Youjin; Spicer, Maria T

    2014-06-01

    Some of the universal characteristics of pre-agricultural hominin diets are strikingly different from the modern human diet. Hominin dietary choices were limited to wild plant and wild animal foods, while the modern diet includes more than 70 % of energy consumed from refined sugars, refined vegetable oils, and highly processed cereals and dairy products. The modern diet, with higher intake of fat has also resulted in a higher ratio of omega-6 (n-6) to omega-3 (n-3) polyunsaturated fatty acids (PUFA), contributing to low-grade chronic inflammation (LGCI) and thus promoting the development of many chronic diseases, including obesity and osteoporosis. In this review, we describe the changes in modern diet, focusing on the kind and amount of consumed fat; explain the shortcomings of the modern diet with regard to inflammatory processes; and delineate the reciprocity between adiposity and inflammatory processes, with inflammation being a common link between obesity and osteoporosis. We present the evidence that overconsumption of n-6 PUFA coupled with under-consumption of n-3 PUFA results in LGCI and, along with the increased presence of reactive oxygen species, leads to a shift in mesenchymal stem cells (precursors for both osteoblasts and adipocytes) lineage commitment toward increased adipogenesis and suppressed osteoblastogenesis. In turn, high n-6 to n-3 PUFA ratios in the modern diet, coupled with increased synthesis of pro-inflammatory cytokines due to adiposity, propagate obesity and osteoporosis by increasing or maintaining LGCI.

  19. 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

  20. Circadian rhythm disruption impairs tissue homeostasis and exacerbates chronic inflammation in the intestine.

    Science.gov (United States)

    Pagel, René; Bär, Florian; Schröder, Torsten; Sünderhauf, Annika; Künstner, Axel; Ibrahim, Saleh M; Autenrieth, Stella E; Kalies, Kathrin; König, Peter; Tsang, Anthony H; Bettenworth, Dominik; Divanovic, Senad; Lehnert, Hendrik; Fellermann, Klaus; Oster, Henrik; Derer, Stefanie; Sina, Christian

    2017-11-01

    Endogenous circadian clocks regulate 24-h rhythms of physiology and behavior. Circadian rhythm disruption (CRD) is suggested as a risk factor for inflammatory bowel disease. However, the underlying molecular mechanisms remain unknown. Intestinal biopsies from Per1/2 mutant and wild-type (WT) mice were investigated by electron microscopy, immunohistochemistry, and bromodeoxyuridine pulse-chase experiments. TNF-α was injected intraperitoneally, with or without necrostatin-1, into Per1/2 mice or rhythmic and externally desynchronized WT mice to study intestinal epithelial cell death. Experimental chronic colitis was induced by oral administration of dextran sodium sulfate. In vitro , caspase activity was assayed in Per1/2-specific small interfering RNA-transfected cells. Wee1 was overexpressed to study antiapoptosis and the cell cycle. Genetic ablation of circadian clock function or environmental CRD in mice increased susceptibility to severe intestinal inflammation and epithelial dysregulation, accompanied by excessive necroptotic cell death and a reduced number of secretory epithelial cells. Receptor-interacting serine/threonine-protein kinase (RIP)-3-mediated intestinal necroptosis was linked to increased mitotic cell cycle arrest via Per1/2-controlled Wee1, resulting in increased antiapoptosis via cellular inhibitor of apoptosis-2. Together, our data suggest that circadian rhythm stability is pivotal for the maintenance of mucosal barrier function. CRD increases intestinal necroptosis, thus rendering the gut epithelium more susceptible to inflammatory processes.-Pagel, R., Bär, F., Schröder, T., Sünderhauf, A., Künstner, A., Ibrahim, S. M., Autenrieth, S. E., Kalies, K., König, P., Tsang, A. H., Bettenworth, D., Divanovic, S., Lehnert, H., Fellermann, K., Oster, H., Derer, S., Sina, C. Circadian rhythm disruption impairs tissue homeostasis and exacerbates chronic inflammation in the intestine. © FASEB.

  1. 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

  2. Indicators of inflammation and cellular damage in chronic asymptomatic or oligosymptomatic alcoholics: correlation with alteration of bilirubin and hepatic and pancreatic enzymes

    Directory of Open Access Journals (Sweden)

    Borini Paulo

    1999-01-01

    Full Text Available Biochemical and hematimetric indicators of inflammation and cell damage were correlated with bilirubin and hepatic and pancreatic enzymes in 30 chronic male alcoholics admitted into psychiatric hospital for detoxification and treatment of alcoholism. Aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, alkaline phosphatase, and total bilirubin were altered, respectively, in 90%, 63%, 87%, 23% and 23% of the cases. None of the indicators of inflammation (lactic dehydrogenase, altered in 16% of the cases; alpha-1 globulin, 24%; alpha-2 globulin, 88%; leucocyte counts, 28% was correlated with alterations of bilirubin or liver enzymes. Lactic dehydrogenase was poorly sensitive for detection of hepatocytic or muscular damage. Alterations of alpha-globulins seemed to have been due more to alcohol metabolism-induced increase of lipoproteins than to inflammation. Among indicators of cell damage, serum iron, increased in 40% of the cases, seemed to be related to liver damage while creatine phosphokinase, increased in 84% of the cases, related to muscle damage. Hyperamylasemia was found in 20% of the cases and significantly correlated with levels of bilirubin, alkaline phosphatase and gamma-glutamyltransferase. It was indicated that injuries of liver, pancreas, salivary glands, and muscle occurred in asymptomatic or oligosymptomatic chronic alcoholics.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    Massa, Christopher B; Groves, Angela M; Jaggernauth, Smita U; Laskin, Debra L; Gow, Andrew J

    2017-08-01

    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 alteration at

  5. The Differential Diagnosis of Two Cases of Chronic Periaortitis

    Directory of Open Access Journals (Sweden)

    Takao Kato

    2013-01-01

    Full Text Available The imaging features of chronic periaortitis resemble those of infected aneurysms. Two illustrative cases of chronic periaortitis, in which the etiologies were caused by IgG4-related disease, are presented. The first case involved a 68-year-old man who presented with vague discomfort in his lower abdomen. The second case was a 42-year-old man who presented with a fever of 38°C and persistent, vague chest discomfort. Both cases demonstrated an increased amount of connective tissue around the aorta in computed tomography images and low intensity in the T2-weighed sequence and high intensity in the diffusion-weighed sequence, suggesting the presence of inflammation, in the magnetic resonance imaging. Negative blood cultures, elevated IgG4 levels, and pathological findings confirmed the diagnosis as chronic periaortitis due to IgG4-related disease. This is a newly recognized syndrome of unknown etiology, characterized by a fibroinflammatory condition, tumefactive lesions, and a dense lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells. Both cases were successfully treated with corticosteroids. Infected aneurysms need to be carefully differentiated from this syndrome in view of the similar imaging features.

  6. [Can the treatment with L-carnitine improve the inflammation in chronic hemodialysis patients?].

    Science.gov (United States)

    Grazi, G; Meriggioli, M; Donati, G

    2004-01-01

    Inflammation in patients on chronic hemodialysis (HD) is related to malnutrition and atherosclerosis; anemia is also often present in these patients. It has been demonstrated that l-carnitina treatment, in addition to reducing the need for erythropoietin (EPO), improves nutritional parameters and cardiac performance. To evaluate the effect of l-carnitine on the inflammatory pathology in patients on chronic HD, we studied 11 patients with no sure signs of malnutrition, flogistic and infective pathologies and with C-reactive protein (CRP) <2 mg/dL. We evaluated at baseline, after 6 and 12 months CRP, serum albumin, hemoglobin (Hb),nPCR and EPO weekly requirement. We observed a reduction in CRP (from 0.88 +/- 0.65 to 0.42 +/- 0.17 mg/dL after 6 months and to 0.50 + 0.36 mg/dL after 12 months), an increase in serum albumin (from 10.9 +/- 1.23 to 2.08 +/- 1.88 and to 11.8 +/- 1.15 g/dL) and an increase in nPCR (from 0.96 +/- 0.09 to 1.15 +/- 0.2 and to 1.16 +/- 0.18 g/kg/die); EPO weekly requirement decreased (from 7363 +/- 2941 to 5909 +/- 3207 units after 6 months and to 5363 +/- 3139 units after 12 months). These results seem to underline a positive effect of l-carnitine on the inflammatory pathology of patients on chronic hemodialytic treatment.

  7. 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

  8. Markers of inflammation and hemodynamic measurements in obesity: Copenhagen City Heart Study

    DEFF Research Database (Denmark)

    Asferg, Camilla; Jensen, Jan S; Marott, Jacob L

    2009-01-01

    BACKGROUND: Low-grade chronic inflammation has been proposed to play a major role in the pathogenesis of hypertension. Low-grade chronic inflammation is also closely associated with obesity, an established causative factor in the development of hypertension. The purpose of this study was to inves......BACKGROUND: Low-grade chronic inflammation has been proposed to play a major role in the pathogenesis of hypertension. Low-grade chronic inflammation is also closely associated with obesity, an established causative factor in the development of hypertension. The purpose of this study...... was to investigate the relationship between two markers of inflammation, C-reactive protein (CRP) and fibrinogen, and blood pressure (BP) and other hemodynamic variables in obese subjects. METHODS: From a large cardiovascular study based in the general population, we selected subjects with a body mass index (BMI...... index (rho: -0.057 to 0.068; P > 0.13). However, fibrinogen and CRP were found to be significantly related to heart rate (rho: 0.127-0.169; P obese subjects from the general population, we found no significant relationships between markers...

  9. Regulation of pulmonary inflammation by mesenchymal cells

    NARCIS (Netherlands)

    Alkhouri, Hatem; Poppinga, Wilfred Jelco; Tania, Navessa Padma; Ammit, Alaina; Schuliga, Michael

    2014-01-01

    Pulmonary inflammation and tissue remodelling are common elements of chronic respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and pulmonary hypertension (PH). In disease, pulmonary mesenchymal cells not only contribute to tissue

  10. 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

  11. A Para-Canalicular Abscess Resembling an Inflamed Chalazion

    Directory of Open Access Journals (Sweden)

    Diamantis Almaliotis

    2013-01-01

    Full Text Available Background. Lacrimal infections by Actinomyces are rare and commonly misdiagnosed for long periods of time. They account for 2% of all lacrimal diseases. Case Report. We report a case of a 70-year-old female patient suffering from a para-canalicular abscess in the medial canthus of the left eye, beside the lower punctum lacrimale, resembling a chalazion. Purulence exited from the punctum lacrimale due to inflammation of the inferior canaliculus (canaliculitis. When pressure was applied to the mass, a second exit of purulence was also observed under the palpebral conjunctiva below the lacrimal caruncle. A surgical excision was performed followed by administration of local antibiotic therapy. The histopathological examination of the extracted mass revealed the existence of actinomycosis. Conclusion. Persistent or recurrent infections and lumps of the eyelids should be thoroughly investigated. Actinomyces as a causative agent should be considered. Differential diagnosis is broad and should include canaliculitis, chalazion, and multiple types of neoplasias. For this reason, in nonconclusive cases, a histopathological examination should be performed.

  12. 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.

  13. Aging, not age-associated inflammation, determines blood pressure and endothelial responses to acute inflammation.

    Science.gov (United States)

    Lane-Cordova, Abbi D; Ranadive, Sushant M; Kappus, Rebecca M; Cook, Marc D; Phillips, Shane A; Woods, Jeffrey A; Wilund, Kenneth R; Baynard, Tracy; Fernhall, Bo

    2016-12-01

    Aging is characterized by a state of chronic, low-grade inflammation that impairs vascular function. Acute inflammation causes additional decrements in vascular function, but these responses are not uniform in older compared with younger adults. We sought to determine if older adults with low levels of baseline inflammation respond to acute inflammation in a manner similar to younger adults. We hypothesized age-related differences in the vascular responses to acute inflammation, but that older adults with low baseline inflammation would respond similarly to younger adults. Inflammation was induced with an influenza vaccine in 96 participants [older = 67 total, 38 with baseline C-reactive protein (CRP) > 1.5 mg/l and 29 with CRP < 1.5 mg/l; younger = 29]; serum inflammatory markers IL-6 and CRP, blood pressure and flow-mediated dilation (FMD) were measured 24 and 48 h later. Younger adults increased IL-6 and CRP more than the collective older adult group and increased pulse pressure, whereas older adults decreased SBP and reduced pulse pressure. The entire cohort decreased FMD from 11.3 ± 0.8 to 8.3 ± 0.7 to 8.7 ± 0.7% in younger and from 5.8 ± 0.3 to 5.0 ± 0.4 to 4.7 ± 0.4% in older adults, P less than 0.05 for main effect. Older adult groups with differing baseline CRP had the same IL-6, blood pressure, and FMD response to acute inflammation, P less than 0.05 for all interactions, but the low-CRP group increased CRP at 24 and 48 h (from 0.5 ± 0.1 to 1.4 ± 0.2 to 1.7 ± 0.3 mg/l), whereas the high-CRP group did not (from 4.8 ± 0.5 to 5.4 ± 0.5 to 5.4 ± 0.6 mg/l), P less than 0.001 for interaction. Aging, not age-related chronic, low-grade inflammation, determines the vascular responses to acute inflammation.

  14. Distinct lipid a moieties contribute to pathogen-induced site-specific vascular inflammation.

    Directory of Open Access Journals (Sweden)

    Connie Slocum

    2014-07-01

    Full Text Available Several successful pathogens have evolved mechanisms to evade host defense, resulting in the establishment of persistent and chronic infections. One such pathogen, Porphyromonas gingivalis, induces chronic low-grade inflammation associated with local inflammatory bone loss and systemic inflammation manifested as atherosclerosis. P. gingivalis expresses an atypical lipopolysaccharide (LPS structure containing heterogeneous lipid A species, that exhibit Toll-like receptor-4 (TLR4 agonist or antagonist activity, or are non-activating at TLR4. In this study, we utilized a series of P. gingivalis lipid A mutants to demonstrate that antagonistic lipid A structures enable the pathogen to evade TLR4-mediated bactericidal activity in macrophages resulting in systemic inflammation. Production of antagonistic lipid A was associated with the induction of low levels of TLR4-dependent proinflammatory mediators, failed activation of the inflammasome and increased bacterial survival in macrophages. Oral infection of ApoE(-/- mice with the P. gingivalis strain expressing antagonistic lipid A resulted in vascular inflammation, macrophage accumulation and atherosclerosis progression. In contrast, a P. gingivalis strain producing exclusively agonistic lipid A augmented levels of proinflammatory mediators and activated the inflammasome in a caspase-11-dependent manner, resulting in host cell lysis and decreased bacterial survival. ApoE(-/- mice infected with this strain exhibited diminished vascular inflammation, macrophage accumulation, and atherosclerosis progression. Notably, the ability of P. gingivalis to induce local inflammatory bone loss was independent of lipid A expression, indicative of distinct mechanisms for induction of local versus systemic inflammation by this pathogen. Collectively, our results point to a pivotal role for activation of the non-canonical inflammasome in P. gingivalis infection and demonstrate that P. gingivalis evades immune

  15. 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.

  16. Obesity-induced DNA released from adipocytes stimulates chronic adipose tissue inflammation and insulin resistance.

    Science.gov (United States)

    Nishimoto, Sachiko; Fukuda, Daiju; Higashikuni, Yasutomi; Tanaka, Kimie; Hirata, Yoichiro; Murata, Chie; Kim-Kaneyama, Joo-Ri; Sato, Fukiko; Bando, Masahiro; Yagi, Shusuke; Soeki, Takeshi; Hayashi, Tetsuya; Imoto, Issei; Sakaue, Hiroshi; Shimabukuro, Michio; Sata, Masataka

    2016-03-01

    Obesity stimulates chronic inflammation in adipose tissue, which is associated with insulin resistance, although the underlying mechanism remains largely unknown. Here we showed that obesity-related adipocyte degeneration causes release of cell-free DNA (cfDNA), which promotes macrophage accumulation in adipose tissue via Toll-like receptor 9 (TLR9), originally known as a sensor of exogenous DNA fragments. Fat-fed obese wild-type mice showed increased release of cfDNA, as determined by the concentrations of single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) in plasma. cfDNA released from degenerated adipocytes promoted monocyte chemoattractant protein-1 (MCP-1) expression in wild-type macrophages, but not in TLR9-deficient (Tlr9 (-/-) ) macrophages. Fat-fed Tlr9 (-/-) mice demonstrated reduced macrophage accumulation and inflammation in adipose tissue and better insulin sensitivity compared with wild-type mice, whereas bone marrow reconstitution with wild-type bone marrow restored the attenuation of insulin resistance observed in fat-fed Tlr9 (-/-) mice. Administration of a TLR9 inhibitory oligonucleotide to fat-fed wild-type mice reduced the accumulation of macrophages in adipose tissue and improved insulin resistance. Furthermore, in humans, plasma ssDNA level was significantly higher in patients with computed tomography-determined visceral obesity and was associated with homeostasis model assessment of insulin resistance (HOMA-IR), which is the index of insulin resistance. Our study may provide a novel mechanism for the development of sterile inflammation in adipose tissue and a potential therapeutic target for insulin resistance.

  17. Anti-Inflammatory Effect of Emblica officinalis in Rodent Models of Acute and Chronic Inflammation: Involvement of Possible Mechanisms

    Directory of Open Access Journals (Sweden)

    Mahaveer Golechha

    2014-01-01

    Full Text Available Emblica officinalis, commonly known as amla in Ayurveda, is unarguably the most important medicinal plant for prevention and treatment of various ailments. The present study investigated the anti-inflammatory activity of hydroalcoholic extract of Emblica officinalis (HAEEO. Acute inflammation in rats was induced by the subplantar injection of carrageenan, histamine, serotonin, and prostaglandin E2 and chronic inflammation was induced by the cotton pellet granuloma. Intraperitoneal (i.p. administration of HAEEO at all the tested doses (300, 500, and 700 mg/kg significantly (P<0.001 inhibited rat paw edema against all phlogistic agents and also reduced granuloma formation. However, at the dose of 700 mg/kg, HAEEO exhibited maximum anti-inflammatory activity in all experimental models, and the effects were comparable to that of the standard anti-inflammatory drugs. Additionally, in paw tissue the antioxidant activity of HAEEO was also measured and it was found that HAEEO significantly (P<0.001 increased glutathione, superoxide dismutase, and catalase activity and subsequently reduced lipid peroxidation evidenced by reduced malondialdehyde. Taken all together, the results indicated that HAEEO possessed potent anti-inflammatory activity and it may hold therapeutic promise in the management of acute and chronic inflammatory conditions.

  18. Targeting Neutrophilic Inflammation using Polymersome-Mediated Cellular Delivery

    OpenAIRE

    Robertson, J.D.; Ward, J.R.; Avila-Olias, M.; Battaglia, G.; Renshaw, S.A.

    2017-01-01

    Neutrophils are key effector cells in inflammation and play an important role in neutralizing invading pathogens. During inflammation resolution, neutrophils undergo apoptosis before they are removed by macrophages, but if apoptosis is delayed, neutrophils can cause extensive tissue damage and chronic disease. Promotion of neutrophil apoptosis is a potential therapeutic approach for treating persistent inflammation, yet neutrophils have proven difficult cells to manipulate experimentally. In ...

  19. Fisetin and Its Role in Chronic Diseases.

    Science.gov (United States)

    Pal, Harish C; Pearlman, Ross L; Afaq, Farrukh

    2016-01-01

    Chronic inflammation is a prolonged and dysregulated immune response leading to a wide variety of physiological and pathological conditions such as neurological abnormalities, cardiovascular diseases, diabetes, obesity, pulmonary diseases, immunological diseases, cancers, and other life-threatening conditions. Therefore, inhibition of persistent inflammation will reduce the risk of inflammation-associated chronic diseases. Inflammation-related chronic diseases require chronic treatment without side effects. Use of traditional medicines and restricted diet has been utilized by mankind for ages to prevent or treat several chronic diseases. Bioactive dietary agents or "Nutraceuticals" present in several fruits, vegetables, legumes, cereals, fibers, and certain spices have shown potential to inhibit or reverse the inflammatory responses and several chronic diseases related to chronic inflammation. Due to safe, nontoxic, and preventive benefits, the use of nutraceuticals as dietary supplements or functional foods has increased in the Western world. Fisetin (3,3',4',7-tetrahydroxyflavone) is a dietary flavonoid found in various fruits (strawberries, apples, mangoes, persimmons, kiwis, and grapes), vegetables (tomatoes, onions, and cucumbers), nuts, and wine that has shown strong anti-inflammatory, anti-oxidant, anti-tumorigenic, anti-invasive, anti-angiogenic, anti-diabetic, neuroprotective, and cardioprotective effects in cell culture and in animal models relevant to human diseases. In this chapter, we discuss the beneficial pharmacological effects of fisetin against different pathological conditions with special emphasis on diseases related to chronic inflammatory conditions.

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

    Directory of Open Access Journals (Sweden)

    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

  1. The relationship between regional abdominal fat distribution and both insulin resistance and subclinical chronic inflammation in non-diabetic adults

    Science.gov (United States)

    2014-01-01

    Objective Obesity is associated with a high risk of insulin resistance (IR) and its metabolic complications. It is still debated that distributions of adipose tissue relate to an excess risk of IR and chronic inflammation in different race. This study was designed to examine the relation between insulin sensitivity, chronic inflammation and central fat distribution in non-diabetic volunteers in Taiwanese. Methods There were 328 volunteers without family history of diabetes mellitus and with normal oral glucose tolerance test enrolled. Total body fat and abdominal fat were measured. Abdominal fat was categorized into intraperitoneal (IP), retroperitoneal (RP) and subcutaneous (SC) fat. The IR index was estimated by homeostatic model assessment. Five inflammatory markers: adiponectin, leptin, tumor necrosing factor-α (TNF-α), resistin and high sensitive CRP (hs-CRP) were measured. Results IR was related to IP fat (r = 0.23, p fat, SC fat or total body fat. After correcting for age and sex, IP fat was the only significant predictor of IR (r2 = 58%, p = 0.001). Leptin showed the strongest relationship with all fat compartments (IP fat: r = 0.44, p = 0.001; RP fat: r = 0.36, p = 0.005, SC fat: r = 0.54, p fat: r = 0.61, p fat (r = 0.29, p = 0.004; r = -0.29, p = 0.005, respectively), but not RP, or SC fat. TNF-α and resistin were not correlated to any fat compartment. After correcting for age and sex, leptin variance was mostly explained by SC fat (41.3%), followed by IP fat (33.6%) and RP fat (25.3%). The hs-CRP and adiponectin variance were mostly explained by IP fat (40% and 49% respectively). Conclusions IP fat is better predictors of IR and subclinical chronic inflammation in Taiwanese adults. A disproportionate accumulation of abdominal fat is associated with increased risk of cardiovascular diseases. PMID:24684833

  2. 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.

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

    Science.gov (United States)

    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.

  4. 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.

  5. The role of chronic acanthosis and subacute inflammation in tumor promotion in CD-1 mice by petroleum middle distillates.

    Science.gov (United States)

    Skisak, C

    1991-07-01

    An initiation-promotion bioassay using CD-1 mice was conducted to examine the role of chronic acanthosis and inflammation in tumor promotion by petroleum middle distillates (MD). Test groups were initiated with 7,12-dimethylbenz[a]anthracene (DMBA). Promotion with MD consisted of twice weekly treatments for 25 weeks with either 25 or 50 microliters, 50 microliters + daily treatment with 15 micrograms dexamethasone, 50 microliters + postapplication washings, or 100 microliters. Three mice from each group were euthanized at 21-day intervals (24 total per group). The skin from interim euthanized mice was examined histopathologically for tumors, acanthosis, and subacute inflammation. Tumor incidence at study termination was as follows: 25 microliters (45%), 50 microliters (43%), 50 microliters + dexamethasone (0%), 50 microliters + washing (70%), and 100 microliters (81%). A correlation of greater than 0.93 was observed at all intervals between tumor incidence and cumulative group mean degrees of acanthosis in interim euthanized mice. The correlation between subacute inflammation at early through midstudy interval weeks and tumor incidence at study termination was poor. These results support the hypothesis that induction of a lasting, albeit mild, hyperplasia is an essential, but not sufficient requirement for tumor promotion. Furthermore, subacute inflammation does not appear to be a significant factor in tumor promotion by petroleum MD.

  6. Genetics Home Reference: chronic granulomatous disease

    Science.gov (United States)

    ... Other common areas of infection in people with chronic granulomatous disease include the skin, liver , and lymph nodes . Inflammation can occur in ... Other common areas of inflammation in people with chronic granulomatous ... and skin. Additionally, granulomas within the gastrointestinal tract can lead ...

  7. Chronic low-grade inflammation, lipid risk factors and mortality in functionally dependent elderly

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    Vasović Olga

    2010-01-01

    Full Text Available Background/Aim. It has been proved that a highly sensitive C-reactive protein (hsCRP can be used as an established marker of chronic inflammation for cardiovascular risk assessment. Since mean values of both low-density cholesterol (LDL-C and high-density lipoprotein cholesterol (HDL-C decrease during aging, the knowledge that increased hsCRP concentration predicts mortality (Mt would influence therapy and treatment outcome. The aim of this study was to examine importance of chronic low grade inflammation and its association with lipid risk factors for all-cause Mt in functionally dependent elderly. Methods. The participants of this longitudinal prospective study were 257 functionally dependent elderly aged 65-99 years. Baseline measurements: anthropometric measurements, blood pressure, fasting plasma total cholesterol (TC, triglyceride (TG, HDL-C, LDL-C, non- HDL-C, hemoglobin A1c (HbA1c were recorded and different lipid ratios were calculated. Inflammation was assessed by the levels of white blood cells, fibrinogen and hsCRP. The participants with hsCRP grater than 10 mg/L were excluded from the study. The residual participants (77.4% women were divided into three groups according to their hsCRP levels: a low (< 1 mg/L, n = 70, average (1 to 3 mg/L, n = 69, and high (3-10 mg/L, n = 69 hsCRP group. Associations of all-cause Mt with different risk factors were examined using logistic regression analysis. Results. The hsCRP level showed a significant positive correlation with waist (r = 0.199, p = 0.004 and hip (r = 0.187, p = 0.007 circumferences, body mass index (r = 0.143, p = 0.040 and serum triglyceride level (r = 0.139, p = 0.045 and significant negative correlation with HDL-C (r = -0.164, p = 0.018. Ratios TC/HDL-C and TG/HDL-C were significantly smaller in the low hsCRP group compared to the average hsCRP group (p = 0.019, p = 0.045, respectively and without significant differences compared with the high hsCRP group. Two years after the

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

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    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

  9. A crucial role for CDC42 in senescence-associated inflammation and atherosclerosis.

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    Takashi K Ito

    Full Text Available Risk factors for atherosclerosis accelerate the senescence of vascular endothelial cells and promote atherogenesis by inducing vascular inflammation. A hallmark of endothelial senescence is the persistent up-regulation of pro-inflammatory genes. We identified CDC42 signaling as a mediator of chronic inflammation associated with endothelial senescence. Inhibition of CDC42 or NF-κB signaling attenuated the sustained up-regulation of pro-inflammatory genes in senescent human endothelial cells. Endothelium-specific activation of the p53/p21 pathway, a key mediator of senescence, also resulted in up-regulation of pro-inflammatory molecules in mice, which was reversed by Cdc42 deletion in endothelial cells. Likewise, endothelial-specific deletion of Cdc42 significantly attenuated chronic inflammation and plaque formation in atherosclerotic mice. While inhibition of NF-κB suppressed the pro-inflammatory responses in acute inflammation, the influence of Cdc42 deletion was less marked. Knockdown of cdc-42 significantly down-regulated pro-inflammatory gene expression and restored the shortened lifespan to normal in mutant worms with enhanced inflammation. These findings indicate that the CDC42 pathway is critically involved in senescence-associated inflammation and could be a therapeutic target for chronic inflammation in patients with age-related diseases without compromising host defenses.

  10. Network-based characterization of inflammation biomarkers, phytochemicals and disease

    Science.gov (United States)

    Chronic inflammation is often a major contributor to the onset and progression of cardiometabolic dysfunction. Whether through effects on the inflammatory response system or independent of inflammation, plant-derived polyphenols comprise a micro-nutrient class important in cardiovascular disease and...

  11. 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.

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

    Science.gov (United States)

    Ruiz-Núñez, Begoña; Pruimboom, Leo; Dijck-Brouwer, D A Janneke; Muskiet, Frits A J

    2013-07-01

    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 inflammatory reaction jeopardizes the high glucose needs of our brain, causing various adaptations, including insulin resistance, functional reallocation of energy-rich nutrients and changing serum lipoprotein composition. The latter aims at redistribution of lipids, modulation of the immune reaction, and active inhibition of reverse cholesterol transport for damage repair. With the advent of the agricultural and industrial revolutions, we have introduced numerous false inflammatory triggers in our lifestyle, driving us to a state of chronic systemic low grade inflammation that eventually leads to typically Western diseases via an evolutionary conserved interaction between our immune system and metabolism. The underlying triggers are an abnormal dietary composition and microbial flora, insufficient physical activity and sleep, chronic stress and environmental pollution. The disturbance of our inflammatory/anti-inflammatory balance is illustrated by dietary fatty acids and antioxidants. The current decrease in years without chronic disease is rather due to "nurture" than "nature," since less than 5% of the typically Western diseases are primary attributable to genetic factors. Resolution of the conflict between environment and our ancient genome might be the only effective manner for "healthy aging," and to achieve this we might have to return to the lifestyle of the Paleolithic era as translated to the 21st century culture. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Fish Oil Supplementation Reduces Heart Levels of Interleukin-6 in Rats with Chronic Inflammation due to Epilepsy

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    Mariana Bocca Nejm

    2017-06-01

    Full Text Available Sudden unexpected death in epilepsy (SUDEP is a major cause of premature death related to epilepsy. The causes of SUDEP remain unknown, but cardiac arrhythmias and asphyxia have been suggested as a major mechanism of this event. Inflammation has been implicated in the pathogenesis of both epilepsy and ventricular arrhythmia, with interleukin-6 (IL-6 being recognized as a crucial orchestrator of inflammatory states. Our group previously reported that levels of IL-6 were increased in the hearts of epileptic rats. In this scenario, anti-inflammatory actions are among the beneficial effects of fish oil dietary supplementation. This investigation revealed that elevated levels of IL-6 in the heart were markedly reduced in epileptic rats that were treated in the long-term with fish oil, suggesting protective anti-inflammatory actions against dangerously high levels of IL-6. Based on these findings, our results suggest beneficial effects of long-term intake of fish oil in reducing the inflammation associated with chronic epilepsy.

  14. 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.

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

    Science.gov (United States)

    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.

  16. Antimicrobial Peptide Human Neutrophil Peptide 1 as a Potential Link Between Chronic Inflammation and Ductal Adenocarcinoma of the Pancreas.

    Science.gov (United States)

    Pausch, Thomas; Adolph, Sarah; Felix, Klaus; Bauer, Andrea S; Bergmann, Frank; Werner, Jens; Hartwig, Werner

    Defensins are antimicrobial peptides playing a role in innate immunity, in epithelial cell regeneration, and in carcinogenesis of inflammation-triggered malignancies. We analyzed this role in pancreatic ductal adenocarcinoma (PDAC) in the context of its association with chronic pancreatitis (CP). Human tissue of healthy pancreas, CP, and PDAC was screened for defensins by immunohistochemistry. Defensin α 1 (human neutrophil peptide 1 [HNP-1]) expression was validated using mass spectrometry and microarray analysis. Human neutrophil peptide 1 expression and influences of proinflammatory cytokines (tumor necrosis factor α, interleukin 1β, and interferon γ) were studied in human pancreatic cancer cells (Colo 357, T3M4, PANC-1) and normal human pancreatic duct epithelial cells (HPDE). Accumulation of HNP-1 in malignant pancreatic ductal epithelia was seen. Spectrometry showed increased expression of HNP-1 in CP and even more in PDAC. At RNA level, no significant regulation was found. In cancer cells, HNP-1 expression was significantly higher than in HPDE. Proinflammatory cytokines significantly led to increased HNP-1 levels in culture supernatants and decreased levels in lysates of cancer cells. In HPDE cytokines significantly decreased HNP-1 levels. Inflammatory regulation of HNP-1 in PDAC tissue and cells indicates that HNP-1 may be a link between chronic inflammation and malignant transformation in the pancreas.

  17. 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.

  18. Role of Brain Inflammation in Epileptogenesis

    OpenAIRE

    Choi, Jieun; Koh, Sookyong

    2008-01-01

    Inflammation is known to participate in the mediation of a growing number of acute and chronic neurological disorders. Even so, the involvement of inflammation in the pathogenesis of epilepsy and seizure-induced brain damage has only recently been appreciated. Inflammatory processes, including activation of microglia and astrocytes and production of proinflammatory cytokines and related molecules, have been described in human epilepsy patients as well as in experimental models of epilepsy. Fo...

  19. Neuropeptides, neurogenic inflammation and complex regional pain syndrome (CRPS).

    Science.gov (United States)

    Birklein, Frank; Schmelz, Martin

    2008-06-06

    This review explains symptoms and nature of neuropeptide signaling and its importance for clinical symptoms of CRPS. Neurogenic inflammation regularly accompanies excitation of primary afferent nociceptors. It has two major components-plasma extravasation and vasodilatation. The most important mediators are the calcitonin gene-related peptide (CGRP) and substance P (SP). After peripheral trauma immune reaction (e.g. cytokines) and the attempts of the tissue to regenerate (e.g. growth factors) sensitize nociceptors and amplify neurogenic inflammation. This cascade of events has been demonstrated in rat models of CRPS. Clinical findings in these animals strongly resemble clinical findings in CRPS, and can be prevented by anti-cytokine and anti-neuropeptide treatment. In CRPS patients, there is meanwhile also plenty of evidence that neurogenic inflammation contributes to clinical presentation. Increased cytokine production was demonstrated, as well as facilitated neurogenic inflammation. Very recently even "non-inflammatory" signs of CRPS (hyperhidrosis, cold skin) have been linked to neuropeptide signaling. Surprisingly, there was even moderately increased neurogenic inflammation in unaffected body regions. This favors the possibility that CRPS patients share genetic similarities. The future search for genetic commonalities will help us to further unravel the "mystery" CRPS.

  20. Management of Anemia of Inflammation in the Elderly

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    Antonio Macciò

    2012-01-01

    Full Text Available Anemia of any degree is recognized as a significant independent contributor to morbidity, mortality, and frailty in elderly patients. Among the broad types of anemia in the elderly a peculiar role seems to be played by the anemia associated with chronic inflammation, which remains the most complex form of anemia to treat. The origin of this nonspecific inflammation in the elderly has not yet been clarified. It seems more plausible that the oxidative stress that accompanies ageing is the real cause of chronic inflammation of the elderly and that the same oxidative stress is actually a major cause of this anemia. The erythropoietic agents have the potential to play a therapeutic role in this patient population. Despite some promising results, rHuEPO does not have a specific indication for the treatment of anemia in the elderly. Moreover, concerns about their side effects have spurred the search for alternatives. Considering the etiopathogenetic mechanisms of anemia of inflammation in the elderly population, an integrated nutritional/dietetic approach with nutraceuticals that can manipulate oxidative stress and related inflammation may prevent the onset of this anemia and its negative impact on patients’ performance and quality of life.

  1. Management of Anemia of Inflammation in the Elderly

    Science.gov (United States)

    Macciò, Antonio; Madeddu, Clelia

    2012-01-01

    Anemia of any degree is recognized as a significant independent contributor to morbidity, mortality, and frailty in elderly patients. Among the broad types of anemia in the elderly a peculiar role seems to be played by the anemia associated with chronic inflammation, which remains the most complex form of anemia to treat. The origin of this nonspecific inflammation in the elderly has not yet been clarified. It seems more plausible that the oxidative stress that accompanies ageing is the real cause of chronic inflammation of the elderly and that the same oxidative stress is actually a major cause of this anemia. The erythropoietic agents have the potential to play a therapeutic role in this patient population. Despite some promising results, rHuEPO does not have a specific indication for the treatment of anemia in the elderly. Moreover, concerns about their side effects have spurred the search for alternatives. Considering the etiopathogenetic mechanisms of anemia of inflammation in the elderly population, an integrated nutritional/dietetic approach with nutraceuticals that can manipulate oxidative stress and related inflammation may prevent the onset of this anemia and its negative impact on patients' performance and quality of life. PMID:23091709

  2. Chronic Pelvic Pain Development and Prostate Inflammation in Strains of Mice With Different Susceptibility to Experimental Autoimmune Prostatitis.

    Science.gov (United States)

    Breser, Maria L; Motrich, Ruben D; Sanchez, Leonardo R; Rivero, Virginia E

    2017-01-01

    Experimental autoimmune prostatitis (EAP) is an autoimmune inflammatory disease of the prostate characterized by peripheral prostate-specific autoimmune responses associated with prostate inflammation. EAP is induced in rodents upon immunization with prostate antigens (PAg) plus adjuvants and shares important clinical and immunological features with the human disease chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). EAP was induced in young NOD, C57BL/6, and BALB/c male mice by immunization with PAg plus complete Freund́s adjuvant. Tactile allodynia was assessed using Von Frey fibers as a measure of pelvic pain at baseline and at different time points after immunization. Using conventional histology, immunohistochemistry, FACS analysis, and protein arrays, an interstrain comparative study of prostate cell infiltration and inflammation was performed. Chronic pelvic pain development was similar between immunized NOD and C57BL/6 mice, although the severity of leukocyte infiltration was greater in the first case. Coversely, minimal prostate cell infiltration was observed in immunized BALB/c mice, who showed no pelvic pain development. Increased numbers of mast cells, mostly degranulated, were detected in prostate samples from NOD and C57BL/6 mice, while lower total counts and resting were observed in BALB/c mice. Prostate tissue from NOD mice revealed markedly increased expression levels of inflammatory cytokines, chemokines, adhesion molecules, vascular endothelial growth factor, and metalloproteinases. Similar results, but to a lesser extent, were observed when analyzing prostate tissue from C57BL/6 mice. On the contrary, the expression of the above mediators was very low in prostate tissue from immunized BALB/c mice, showing significantly slight increments only for CXCL1 and IL4. Our results provide new evidence indicating that NOD, C57BL/6, and BALB/c mice develop different degrees of chronic pelvic pain, type, and amount of prostate cell infiltration

  3. Chronic gastritis - an update.

    Science.gov (United States)

    Varbanova, Mariya; Frauenschläger, Katrin; Malfertheiner, Peter

    2014-12-01

    Helicobacter pylori is the main aetiologic factor for chronic gastritis worldwide. The degree of inflammation and the evolution of this form of chronic gastritis can vary largely depending on bacterial virulence factors, host susceptibility factors and environmental conditions. Autoimmune gastritis is another cause of chronic inflammation in the stomach, which can occur in all age groups. This disease presents typically with vitamin B12 deficiency and pernicious anaemia. The presence of anti-parietal cell antibodies is highly specific for the diagnosis. The role of H. pylori as a trigger for autoimmune gastritis remains uncertain. Other rare conditions for chronic gastritis are chronic inflammatory conditions such as Crohn's disease or on the background of lymphocytic or collagenous gastroenteropathies. Copyright © 2014. Published by Elsevier Ltd.

  4. The common parasite Toxoplasma gondii induces prostatic inflammation and microglandular hyperplasia in a mouse model.

    Science.gov (United States)

    Colinot, Darrelle L; Garbuz, Tamila; Bosland, Maarten C; Wang, Liang; Rice, Susan E; Sullivan, William J; Arrizabalaga, Gustavo; Jerde, Travis J

    2017-07-01

    Inflammation is the most prevalent and widespread histological finding in the human prostate, and associates with the development and progression of benign prostatic hyperplasia and prostate cancer. Several factors have been hypothesized to cause inflammation, yet the role each may play in the etiology of prostatic inflammation remains unclear. This study examined the possibility that the common protozoan parasite Toxoplasma gondii induces prostatic inflammation and reactive hyperplasia in a mouse model. Male mice were infected systemically with T. gondii parasites and prostatic inflammation was scored based on severity and focality of infiltrating leukocytes and epithelial hyperplasia. We characterized inflammatory cells with flow cytometry and the resulting epithelial proliferation with bromodeoxyuridine (BrdU) incorporation. We found that T. gondii infects the mouse prostate within the first 14 days of infection and can establish parasite cysts that persist for at least 60 days. T. gondii infection induces a substantial and chronic inflammatory reaction in the mouse prostate characterized by monocytic and lymphocytic inflammatory infiltrate. T. gondii-induced inflammation results in reactive hyperplasia, involving basal and luminal epithelial proliferation, and the exhibition of proliferative inflammatory microglandular hyperplasia in inflamed mouse prostates. This study identifies the common parasite T. gondii as a new trigger of prostatic inflammation, which we used to develop a novel mouse model of prostatic inflammation. This is the first report that T. gondii chronically encysts and induces chronic inflammation within the prostate of any species. Furthermore, T. gondii-induced prostatic inflammation persists and progresses without genetic manipulation in mice, offering a powerful new mouse model for the study of chronic prostatic inflammation and microglandular hyperplasia. © 2017 Wiley Periodicals, Inc.

  5. Coordinated and interactive expression of genes of lipid metabolism and inflammation in adipose tissue and liver during metabolic overload.

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    Wen Liang

    Full Text Available BACKGROUND: Chronic metabolic overload results in lipid accumulation and subsequent inflammation in white adipose tissue (WAT, often accompanied by non-alcoholic fatty liver disease (NAFLD. In response to metabolic overload, the expression of genes involved in lipid metabolism and inflammatory processes is adapted. However, it still remains unknown how these adaptations in gene expression in expanding WAT and liver are orchestrated and whether they are interrelated. METHODOLOGY/PRINCIPAL FINDINGS: ApoE*3Leiden mice were fed HFD or chow for different periods up to 12 weeks. Gene expression in WAT and liver over time was evaluated by micro-array analysis. WAT hypertrophy and inflammation were analyzed histologically. Bayesian hierarchical cluster analysis of dynamic WAT gene expression identified groups of genes ('clusters' with comparable expression patterns over time. HFD evoked an immediate response of five clusters of 'lipid metabolism' genes in WAT, which did not further change thereafter. At a later time point (>6 weeks, inflammatory clusters were induced. Promoter analysis of clustered genes resulted in specific key regulators which may orchestrate the metabolic and inflammatory responses in WAT. Some master regulators played a dual role in control of metabolism and inflammation. When WAT inflammation developed (>6 weeks, genes of lipid metabolism and inflammation were also affected in corresponding livers. These hepatic gene expression changes and the underlying transcriptional responses in particular, were remarkably similar to those detected in WAT. CONCLUSION: In WAT, metabolic overload induced an immediate, stable response on clusters of lipid metabolism genes and induced inflammatory genes later in time. Both processes may be controlled and interlinked by specific transcriptional regulators. When WAT inflammation began, the hepatic response to HFD resembled that in WAT. In all, WAT and liver respond to metabolic overload by

  6. Magnesium deficiency and increased inflammation: current perspectives

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    Nielsen FH

    2018-01-01

    Full Text Available Forrest H Nielsen Research Nutritionist Consultant, Grand Forks, ND, USA Abstract: Animal studies have shown that magnesium deficiency induces an inflammatory response that results in leukocyte and macrophage activation, release of inflammatory cytokines and acute-phase proteins, and excessive production of free radicals. Animal and in vitro studies indicate that the primary mechanism through which magnesium deficiency has this effect is through increasing cellular Ca2+, which is the signal that results in the priming of cells to give the inflammatory response. Primary pro-inflammatory cytokines such as tumor necrosis factor-α and interleukin (IL-1; the messenger cytokine IL-6; cytokine responders E-selectin, intracellular adhesion molecule-1 and vascular cell adhesion molecule-1; and acute-phase reactants C-reactive protein and fibrinogen have been determined to associate magnesium deficiency with chronic low-grade inflammation (inflammatory stress. When magnesium dietary intake, supplementation, and/or serum concentration suggest/s the presence of magnesium deficiency, it often is associated with low-grade inflammation and/or with pathological conditions for which inflammatory stress is considered a risk factor. When magnesium intake, supplementation, and/or serum concentration suggest/s an adequate status, magnesium generally has not been found to significantly affect markers of chronic low-grade inflammation or chronic disease. The consistency of these findings can be modified by other nutritional and metabolic factors that affect inflammatory and oxidative stress. In spite of this, findings to date provide convincing evidence that magnesium deficiency is a significant contributor to chronic low-grade inflammation that is a risk factor for a variety of pathological conditions such as cardiovascular disease, hypertension, and diabetes. Because magnesium deficiency commonly occurs in countries where foods rich in magnesium are not consumed in

  7. Effect of Helicobacter pylori infection on chronic periodontitis by the change of microecology and inflammation.

    Science.gov (United States)

    Hu, Zhekai; Zhang, Yu; Li, Zhiyu; Yu, Yuedi; Kang, Wenyan; Han, Yingnan; Geng, Xiwen; Ge, Shaohua; Sun, Yundong

    2016-10-11

    Helicobacter pylori (H. pylori), a pathogen inducing peptic disease, is recently found to be binding to the progress of periodontitis. Most previous studies are case-controlled, and they investigate the risk of H. pylori infection in disease the development of while few studies evaluate the correlation between H. pylori and periodontal pathogens. Therefore, we investigated the correlation between H. pylori infection with periodontal parameters, periodontal pathogens and inflammation. The results indicated that patients with H. pylori showed significantly higher probing depth and attachment loss than those without (p periodontitis-related molecules Wnt5a, interleukin 8 (IL-8), interleukin 6 (IL-6) and interferon gamma (IFN-γ) significantly increased (p periodontal pathogens and aggravate the progress of chronic periodontitis.

  8. Nano-based theranostics for chronic obstructive lung diseases: challenges and therapeutic potential

    OpenAIRE

    Vij, Neeraj

    2011-01-01

    The major challenges in the delivery and therapeutic efficacy of nano-delivery systems in chronic obstructive airway conditions is airway defense, severe inflammation and mucous hypersecretion. Chronic airway inflammation and mucous hypersecretion are hallmarks of chronic obstructive airway diseases, including asthma, COPD (chronic obstructive pulmonary disease) and CF (cystic fibrosis). Distinct etiologies drive inflammation and mucous hyper secretion in these diseases, that is further induc...

  9. 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.

  10. T-cell activation promotes tumorigenesis in inflammation-associated cancer

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    Lairmore Michael

    2009-12-01

    Full Text Available Abstract Chronic inflammation has long been associated with a wide range of malignancies, is now widely accepted as a risk factor for development of cancer, and has been implicated as a promoter of a variety of cancers including hematopoietic malignancies. We have described a mouse model uniquely suited to examine the link between inflammation and lymphoma in which the Tax oncogene, expressed in activated T and NK cells, perpetuates chronic inflammation that begins as microscopic intraepithelial lesions and develops into inflammatory nodules, subcutaneous tumors, and large granular lymphocytic leukemia. The use of bioluminescent imaging in these mice has expanded our ability to interrogate aspects of inflammation and tumorigenesis non-invasively. Here we demonstrate that bioluminescence induction in these mice correlated with inflammation resulting from wounding, T cell activation, and exposure to chemical agents. In experiments in which long-term effects of inflammation on disease outcome were monitored, the development of lymphoma was promoted by an inflammatory stimulus. Finally we demonstrated that activation of T-cells in T-cell receptor (TCR transgenic TAX-LUC animals dramatically exacerbated the development of subcutaneous TCR- CD16+ LGL tumors. The role of activated T-cells and acquired immunity in inflammation-associated cancers is broadly applicable to hematopoietic malignancies, and we propose these mice will be of use in dissecting mechanisms by which activated T-cells promote lymphomagenesis in vivo.

  11. Imaging manifestations of acquired elastopathy resembling pseudoxanthoma elasticum in patients with beta thalassaemia major and sickle cell disease

    International Nuclear Information System (INIS)

    Narayana, Harish; Cheng, Ken; Lau, Ken; Harish, Radhika; Bowden, Donald K.

    2016-01-01

    Development of an acquired systemic elastopathy resembling pseudoxanthoma elasticum in patients with chronic haemoglobinopathies such as beta thalassaemia major and sickle cell disease is well documented. There is paucity of any comprehensive literature on the radiological manifestations of this entity. This pictorial review aims to describe and illustrate the multi system and multi modality imaging findings of this condition.

  12. 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.

  13. Natural products to target inflammation

    NARCIS (Netherlands)

    Allijn, Iris Eva

    2016-01-01

    Chapter 1 Most Western lifestyle diseases such as type 2 diabetes mellitus, cardiovascular disease and cancer have a chronic inflammatory process at its base. Therefore, inflammation is an important therapeutic target. Due to their potency, steroidal drugs dominate the current treatment of

  14. TIM-3 is not essential for development of airway inflammation induced by house dust mite antigens

    Directory of Open Access Journals (Sweden)

    Yoshihisa Hiraishi

    2016-10-01

    Conclusions: Our findings indicate that, in mice, TIM-3 is not essential for development of HDM-induced acute or chronic allergic airway inflammation, although it appears to be involved in reduced lymphocyte recruitment during HDM-induced chronic allergic airway inflammation.

  15. [Chronic otitis mediaChronic Otitis Media].

    Science.gov (United States)

    Kohles, N; Schulz, T; Eßer, D

    2015-11-01

    There are 2 different kinds of chronic otitis media: Otitis media chronica mesotympanalis and otitis media chronica epitympanalis (cholesteatoma). The incidence of chronic otitis media as reported in literature differs in a wide range. The incidence rates vary between 0.45 and 46%. Both, otitis media chronica mesotympanalis and cholesteatoma, lead to eardrum perforation due to lengthy and recurring inflammations. Furthermore, chronic otitis media is characterized by frequently recurring otorrhea and conductive hearing loss. Georg Thieme Verlag KG Stuttgart · New York.

  16. 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.

  17. The effect of cardioprotective diet rich with natural antioxidants on chronic inflammation and oxidized LDL during cardiac rehabilitation in patients after acute myocardial infarction

    Directory of Open Access Journals (Sweden)

    Polona Mlakar

    2015-06-01

    Conclusions: The addition of cardioprotective diet, rich with natural antioxidants, to physical activity as a part of a CR program, positively modifies not just classic risk factors and exercise capacity, but also diminishes chronic inflammation markers. These effects, and oxLDL decline were most prominent in nonsmoking patients.

  18. 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.

  19. 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...

  20. Mechanisms regulating skin immunity and inflammation.

    Science.gov (United States)

    Pasparakis, Manolis; Haase, Ingo; Nestle, Frank O

    2014-05-01

    Immune responses in the skin are important for host defence against pathogenic microorganisms. However, dysregulated immune reactions can cause chronic inflammatory skin diseases. Extensive crosstalk between the different cellular and microbial components of the skin regulates local immune responses to ensure efficient host defence, to maintain and restore homeostasis, and to prevent chronic disease. In this Review, we discuss recent findings that highlight the complex regulatory networks that control skin immunity, and we provide new paradigms for the mechanisms that regulate skin immune responses in host defence and in chronic inflammation.

  1. Sinonasal inflammation in COPD

    DEFF Research Database (Denmark)

    Håkansson, Kåre; Konge, L; Thomsen, Simon Francis

    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. Acupuncture for chronic pelvic inflammatory disease: A systematic review protocol.

    Science.gov (United States)

    Cheng, Ying; Yuan, Youcai; Jin, Yuhao; Xu, Na; Guo, Taipin

    2018-03-01

    Chronic pelvic inflammation disease (PID) is a difficult-to-treat gynecological disorder with complex etiologies. Acupuncture has been applied widely for treating chronic pelvic inflammation or chronic pelvic pain symptoms in China. The aim of this review is to undertake a systematic review to estimate the effectiveness and safety of acupuncture on chronic PID. A literature search will be conducted electronically with date up to October 2018 in MEDLINE, Cochrane Library, EBASE, and CNKI databases, using combination subject terms of chronic pelvic pain (or chronic pelvic inflammation, and chronic pelvic pain symptoms, etc.) and acupuncture related treatment. Also duplicates will be removed. The primary outcomes consisted of improvement rate and pain relief. Secondary outcomes include the recurrence rate and side effects, such as pneumothorax, bleeding, serious discomfort, subcutaneous nodules, and infection. Systematic reviews and databases will be searched for randomized controlled trials on acupuncture for chronic PID with acupuncture treatment will be included. Cochrane RevMan V5.3.5 risk of bias assessment tool will be implemented for risk of bias evaluation, data synthesis, meta-analyses, and subgroup analysis while condition is met. Mean difference (MD), standard mean difference (SMD), and dichotomous data will be used to present continuous outcomes. This study will generate a comprehensive review of current evidence of acupuncture for chronic pelvic inflammation diseases. The study will provide updated evidence to evaluate the effectiveness and side effects of acupuncture for chronic pelvic inflammation disease. CRD42018087950.

  3. Chronic Meningococcaemia

    African Journals Online (AJOL)

    clinical features, complications, laboratory findings and treatment of this condition are discussed. The resemblance, both clinically and histologically, to allergic vasculitis is stressed. S. Air. Med. J., 48, 2154 (1974). Chronic meningococcaemia is an uncommon condition today, but was well recognised in the early decades of.

  4. Pre-clinical efficacy assessment of Malva sylvestris on chronic skin inflammation.

    Science.gov (United States)

    Prudente, Arthur S; Sponchiado, Graziela; Mendes, Daniel A G B; Soley, Bruna S; Cabrini, Daniela A; Otuki, Michel F

    2017-09-01

    In the search for improved quality of life, the treatment of skin diseases like psoriasis (hyperproliferative disease) is valid, since it causes huge social discomfort to the patient. In this context, earlier studies showed that Malva sylvestris L. has anti-inflammatory activity demonstrated by acute animal models of skin inflammation, becoming a promising target for further studies. The present investigation aimed to verify the effect of hydroalcoholic extract of M. sylvestris (HEMS) on the chronic inflammatory and hyperproliferative response caused by multiple applications of 12-O-tetradecanoylphorbol-13-acetate (TPA) on mouse ears. Topical application of HEMS reduced oedema, leukocyte migration (mono- and polymorphonuclear cells) and keratinocyte hyperproliferation, confirmed by histology and proliferating cell nuclear antigen (PCNA) immunostaining. It was found that the anti-inflammatory effects of the extract did not involve the glucocorticoid system, and its incubation with HaCaT keratinocytes caused low toxicity and reduced cell proliferation by apoptosis. Thus, HEMS proved to be effective as an anti-psoriatic therapy, with the ability to prevent keratinocyte hyperproliferation and with low toxicity by topical application. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  5. Bifidobacterium breve and Lactobacillus rhamnosus treatment is as effective as budesonide at reducing inflammation in a murine model for chronic asthma.

    Science.gov (United States)

    Sagar, Seil; Morgan, Mary E; Chen, Si; Vos, Arjan P; Garssen, Johan; van Bergenhenegouwen, Jeroen; Boon, Louis; Georgiou, Niki A; Kraneveld, Aletta D; Folkerts, Gert

    2014-04-16

    Asthma is estimated to affect as many as 300 million people worldwide and its incidence and prevalence are rapidly increasing throughout the world, especially in children and within developing countries. Recently, there has been a growing interest in the use of potentially beneficial bacteria for allergic diseases. This study is aimed at exploring the therapeutic effects of long-term treatment with two different beneficial bacterial strains (Bifidobacterium breve M-16 V and Lactobacillus rhamnosus NutRes1) and a glucocorticoid (budesonide), as a reference treatment, on inflammatory response in a murine model for chronic allergic asthma. To mimic the chronic disease in asthmatic patients, we used the murine ovalbumin-induced asthma model combined with prolonged allergen exposure. Airway function; pulmonary airway inflammation; airway remodelling, mRNA expression of pattern recognition receptors, Th-specific cytokines and transcription factors in lung tissue; mast cell degranulation; in vitro T cell activation; and expression of Foxp3 in blood Th cells were examined. Lactobacillus rhamnosus reduced lung resistance to a similar extent as budesonide treatment in chronically asthmatic mice. Pulmonary airway inflammation, mast cell degranulation, T cell activation and airway remodelling were suppressed by all treatments. Beneficial bacteria and budesonide differentially modulated the expression of toll-like receptors (TLRs), nod-like receptors (NLRs), cytokines and T cell transcription factors. Bifidobacterium breve induced regulatory T cell responses in the airways by increasing Il10 and Foxp3 transcription in lung tissue as well as systemic by augmenting the mean fluorescence intensity of Foxp3 in blood CD4+ T cells. These findings show that Bifidobacterium breve M-16 V and Lactobacillus rhamnosus NutRes1 have strong anti-inflammatory properties that are comparable to budesonide and therefore may be beneficial in the treatment of chronic asthma.

  6. Infection, inflammation and exercise in cystic fibrosis

    Science.gov (United States)

    2013-01-01

    Regular exercise is positively associated with health. It has also been suggested to exert anti-inflammatory effects. In healthy subjects, a single exercise session results in immune cell activation, which is characterized by production of immune modulatory peptides (e.g. IL-6, IL-8), a leukocytosis and enhanced immune cell functions. Upon cessation of exercise, immune activation is followed by a tolerizing phase, characterized by a reduced responsiveness of immune cells. Regular exercise of moderate intensity and duration has been shown to exert anti-inflammatory effects and is associated with a reduced disease incidence and viral infection susceptibility. Specific exercise programs may therefore be used to modify the course of chronic inflammatory and infectious diseases such as cystic fibrosis (CF). Patients with CF suffer from severe and chronic pulmonary infections and inflammation, leading to obstructive and restrictive pulmonary disease, exercise intolerance and muscle cachexia. Inflammation is characterized by a hyper-inflammatory phenotype. Patients are encouraged to engage in exercise programs to maintain physical fitness, quality of life, pulmonary function and health. In this review, we present an overview of available literature describing the association between regular exercise, inflammation and infection susceptibility and discuss the implications of these observations for prevention and treatment of inflammation and infection susceptibility in patients with CF. PMID:23497303

  7. Exercise alleviates depression related systemic inflammation in ...

    African Journals Online (AJOL)

    Exercise alleviates depression related systemic inflammation in chronic obstructive pulmonary disease patients. ... African Health Sciences ... Currently, physical activity is an important lifestyle factor that has the potential to modify inflammatory ...

  8. [Vascular depression in the elderly. Does inflammation play a role?].

    Science.gov (United States)

    Viscogliosi, Giovanni; Andreozzi, Paola; Chiriac, Iulia Maria; Ettorre, Evaristo; Vulcano, Achiropita; Servello, Adriana; Marigliano, Benedetta; Marigliano, Vincenzo

    2011-06-01

    Vascular depression in the elderly. Does inflammation play a role?Depression is the most common comorbidity in the elderly, and it is a major determinant of disability. The late-onset depression in highly associated to cardiovascular disease. Depressive symptoms may follow vascular brain damage, especially when mood regulating areas are affected. However depression is strongly associated to vascular disease even when there is no manifest brain damage. Recently great attention has been given to chronic inflammation, both related to depression and vascular disease. Both experimental and clinical evidence shows that a rise in the concentrations of proinflammatory cytokines and glucocorticoids in depressed patients is associated with defect in serotonergic function. Chronic inflammation may underlie many forms of depression associated with vascular disease and metabolic syndrome. The importance of the inflammation hypothesis of depression lies is that psychotropic drugs may have central anti-inflammatory action, and that new generation of central anti-inflammatory drugs may be useful in depression treatment.

  9. PPARs, Obesity, and Inflammation

    Directory of Open Access Journals (Sweden)

    Rinke Stienstra

    2007-01-01

    Full Text Available The worldwide prevalence of obesity and related metabolic disorders is rising rapidly, increasing the burden on our healthcare system. Obesity is often accompanied by excess fat storage in tissues other than adipose tissue, including liver and skeletal muscle, which may lead to local insulin resistance and may stimulate inflammation, as in steatohepatitis. In addition, obesity changes the morphology and composition of adipose tissue, leading to changes in protein production and secretion. Some of these secreted proteins, including several proinflammatory mediators, may be produced by macrophages resident in the adipose tissue. The changes in inflammatory status of adipose tissue and liver with obesity feed a growing recognition that obesity represents a state of chronic low-level inflammation. Various molecular mechanisms have been implicated in obesity-induced inflammation, some of which are modulated by the peroxisome proliferator-activated receptors (PPARs. PPARs are ligand-activated transcription factors involved in the regulation of numerous biological processes, including lipid and glucose metabolism, and overall energy homeostasis. Importantly, PPARs also modulate the inflammatory response, which makes them an interesting therapeutic target to mitigate obesity-induced inflammation and its consequences. This review will address the role of PPARs in obesity-induced inflammation specifically in adipose tissue, liver, and the vascular wall.

  10. Soluble Receptor for Advanced Glycation End Product Ameliorates Chronic Intermittent Hypoxia Induced Renal Injury, Inflammation, and Apoptosis via P38/JNK Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Xu Wu

    2016-01-01

    Full Text Available Obstructive sleep apnea (OSA associated chronic kidney disease is mainly caused by chronic intermittent hypoxia (CIH triggered tissue damage. Receptor for advanced glycation end product (RAGE and its ligand high mobility group box 1 (HMGB1 are expressed on renal cells and mediate inflammatory responses in OSA-related diseases. To determine their roles in CIH-induced renal injury, soluble RAGE (sRAGE, the RAGE neutralizing antibody, was intravenously administered in a CIH model. We also evaluated the effect of sRAGE on inflammation and apoptosis. Rats were divided into four groups: (1 normal air (NA, (2 CIH, (3 CIH+sRAGE, and (4 NA+sRAGE. Our results showed that CIH accelerated renal histological injury and upregulated RAGE-HMGB1 levels involving inflammatory (NF-κB, TNF-α, and IL-6, apoptotic (Bcl-2/Bax, and mitogen-activated protein kinases (phosphorylation of P38, ERK, and JNK signal transduction pathways, which were abolished by sRAGE but p-ERK. Furthermore, sRAGE ameliorated renal dysfunction by attenuating tubular endothelial apoptosis determined by immunofluorescence staining of CD31 and TUNEL. These findings suggested that RAGE-HMGB1 activated chronic inflammatory transduction cascades that contributed to the pathogenesis of the CIH-induced renal injury. Inhibition of RAGE ligand interaction by sRAGE provided a therapeutic potential for CIH-induced renal injury, inflammation, and apoptosis through P38 and JNK pathways.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Comparative effects of enzogenol and vitamin C supplementation versus vitamin C alone on endothelial function and biochemical markers of oxidative stress and inflammation in chronic smokers.

    Science.gov (United States)

    Young, Joanna M; Shand, Brett I; McGregor, Patrice M; Scott, Russell S; Frampton, Christopher M

    2006-01-01

    Chronic smoking is associated with endothelial dysfunction and inflammation, with oxidative stress contributing to both these processes. In this study, we investigated the effect of combined antioxidant treatment with Enzogenol, a flavonoid extract from the bark of Pinus radiata and vitamin C, over and above vitamin C alone, on endothelial function, plasma markers of inflammation and oxidative stress, blood pressure (BP) and anthropometrics. Forty-four chronic smokers without established cardiovascular disease were assigned randomly to receive either 480 mg Enzogenol and 60 mg vitamin C, or 60 mg vitamin C alone daily for 12 weeks. Endothelial function in the brachial artery was assessed by flow-mediated vasodilation (FMD). FMD improved in both treatment groups (p effect on macrovascular endothelial function over and above that seen in the vitamin C alone group. However, Enzogenol did demonstrate additional favourable effects on protein oxidative damage and fibrinogen levels.

  13. 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

    Directory of Open Access Journals (Sweden)

    Sattar Naveed

    2011-01-01

    Full Text Available 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 P 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.

  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. 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.

  16. Inhibition of Inflammation-Associated Olfactory Loss by Etanercept in an Inducible Olfactory Inflammation Mouse Model.

    Science.gov (United States)

    Jung, Yong Gi; Lane, Andrew P

    2016-06-01

    To determine the effect of a soluble human tumor necrosis factor alpha (TNF-α) receptor blocker (etanercept) on an inducible olfactory inflammation (IOI) mouse model. An in vivo study using a transgenic mouse model. Research laboratory. To study the impact of chronic inflammation on the olfactory system, a transgenic mouse model of chronic rhinosinusitis-associated olfactory loss was utilized (IOI mouse), expressing TNF-α in a temporally controlled fashion within the olfactory epithelium. In one group of mice (n = 4), etanercept was injected intraperitoneally (100 μg/dose, 3 times/week) concurrent with a 2-week period of TNF-α expression. A second group of mice (n = 2) underwent induction of TNF-α expression for 8 weeks, with etanercept treatment administered during the final 2 weeks of inflammation. Olfactory function was assayed by elecro-olfactogram (EOG), and olfactory tissue was processed for histology and immunohistochemical staining. Each group was compared with an equal-number control group. Compared with nontreated IOI mice, etanercept-treated IOI mice showed significantly improved EOG responses after 2 weeks (P loss of olfactory epithelium and no EOG response in nontreated IOI mice. However, in etanercept-treated mice, regeneration of olfactory epithelium was observed. Concomitant administration of etanercept in IOI mice results in interruption of TNF-α-induced olfactory loss and induction of neuroepithelial regeneration. This demonstrates that etanercept has potential utility as a tool for elucidating the role of TNF-α in other olfactory inflammation models. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.

  17. GFAP and Fos immunoreactivity in lumbo-sacral spinal cord and medulla oblongata after chronic colonic inflammation in rats

    Science.gov (United States)

    Sun, Yi-Ning; Luo, Jin-Yan; Rao, Zhi-Ren; Lan, Li; Duan, Li

    2005-01-01

    AIM: To investigate the response of astrocytes and neurons in rat lumbo-sacral spinal cord and medulla oblongata induced by chronic colonic inflammation, and the relationship between them. METHODS: Thirty-three male Sprague-Dawley rats were randomly divided into two groups: experimental group (n = 17), colonic inflammation was induced by intra-luminal administration of trinitrobenzenesulfonic acid (TNBS); control group (n = 16), saline was administered intra-luminally. After 3, 7, 14, and 28 d of administration, the lumbo-sacral spinal cord and medulla oblongata were removed and processed for anti-glial fibrillary acidic protein (GFAP), Fos and GFAP/Fos immunohistochemistry. RESULTS: Activated astrocytes positive for GFAP were mainly distributed in the superficial laminae (laminae I-II) of dorsal horn, intermediolateral nucleus (laminae V), posterior commissural nucleus (laminae X) and anterolateral nucleus (laminae IX). Fos-IR (Fos-immunoreactive) neurons were mainly distributed in the deeper laminae of the spinal cord (laminae III-IV, V-VI). In the medulla oblongata, both GFAP-IR astrocytes and Fos-IR neurons were mainly distributed in the medullary visceral zone (MVZ). The density of GFAP in the spinal cord of experimental rats was significantly higher after 3, 7, and 14 d of TNBS administration compared with the controls (50.4±16.8, 29.2±6.5, 24.1±5.6, P0.05). CONCLUSION: Astrocytes in spinal cord and medulla oblongata can be activated by colonic inflammation. The activated astrocytes are closely related to Fos-IR neurons. With the recovery of colonic inflammation, the activity of astrocytes in the spinal cord and medulla oblongata is reduced. PMID:16097052

  18. Systemic low-grade inflammation in post-traumatic stress disorder: a systematic review

    Directory of Open Access Journals (Sweden)

    Speer K

    2018-03-01

    Full Text Available Kathryn Speer,1 Dominic Upton,2 Stuart Semple,1,3 Andrew McKune1–4 1Discipline of Sport and Exercise Science, Faculty of Health, University of Canberra, Canberra, ACT, Australia; 2Faculty of Health, University of Canberra, Canberra, ACT, Australia; 3Research Institute for Sport and Exercise, University of Canberra, Canberra, ACT, Australia; 4Discipline of Biokinetics, Exercise and Leisure Sciences, School of Health Sciences, University of KwaZulu Natal, Durban, South Africa Abstract: Studies examining post-traumatic stress disorder (PTSD have either emphasized a relationship between PTSD and a systemically pro-inflammatory state or identified a link between PTSD and chronic disease. The aim of this study was to evaluate the evidence for a relationship between individuals with PTSD and systemic low-grade inflammation that has been proposed to underlie chronic disease development in this population. The authors conducted a systematic review of the literature (January 2006 to April 2017 in accordance with the PRISMA statement in the following four databases: PubMed, MEDLINE, PsycINFO, and SPORTDiscus with Full Text. The search strategy was limited to articles published in peer-reviewed journals and to human studies. Nine studies measuring systemic inflammation and discussing its role in chronic disease development were selected for inclusion in this review. The association between markers of systemic inflammation and PTSD was evaluated by the measurement of a variety of systemic inflammatory markers including acute-phase proteins, complement proteins, pro- and anti-inflammatory cytokines, natural killer cells, and white blood cells. In general, systemic inflammatory biomarkers were elevated across the studies in the PTSD groups. There is evidence that PTSD is underpinned by the presence of a systemic low-grade inflammatory state. This inflammation may be the mechanism associated with increased risk for chronic disease in the PTSD population. From

  19. 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.

  20. Hippocampal structure and function are maintained despite severe innate peripheral inflammation.

    Science.gov (United States)

    Süß, Patrick; Kalinichenko, Liubov; Baum, Wolfgang; Reichel, Martin; Kornhuber, Johannes; Loskarn, Sandra; Ettle, Benjamin; Distler, Jörg H W; Schett, Georg; Winkler, Jürgen; Müller, Christian P; Schlachetzki, Johannes C M

    2015-10-01

    Chronic peripheral inflammation mediated by cytokines such as TNFα, IL-1β, and IL-6 is associated with psychiatric disorders like depression and anxiety. However, it remains elusive which distinct type of peripheral inflammation triggers neuroinflammation and affects hippocampal plasticity resulting in depressive-like behavior. We hypothesized that chronic peripheral inflammation in the human TNF-α transgenic (TNFtg) mouse model of rheumatoid arthritis spreads into the central nervous system and induces depressive state manifested in specific behavioral pattern and impaired adult hippocampal neurogenesis. TNFtg mice showed severe erosive arthritis with increased IL-1β and IL-6 expression in tarsal joints with highly elevated human TNF-α levels in the serum. Intriguingly, IL-1β and IL-6 mRNA levels were not altered in the hippocampus of TNFtg mice. In contrast to the pronounced monocytosis in joints and spleen of TNFtg mice, signs of hippocampal microgliosis or astrocytosis were lacking. Furthermore, locomotion was impaired, but there was no locomotion-independent depressive behavior in TNFtg mice. Proliferation and maturation of hippocampal neural precursor cells as well as survival of newly generated neurons were preserved in the dentate gyrus of TNFtg mice despite reduced motor activity and peripheral inflammatory signature. We conclude that peripheral inflammation in TNFtg mice is mediated by chronic activation of the innate immune system. However, severe peripheral inflammation, though impairing locomotor activity, does not elicit depressive-like behavior. These structural and functional findings indicate the maintenance of hippocampal immunity, cellular plasticity, and behavior despite peripheral innate inflammation. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Inflammatory biomarkers and comorbidities in chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Thomsen, Mette; Dahl, Morten; Lange, Peter

    2012-01-01

    Patients with chronic obstructive pulmonary disease (COPD) have evidence of systemic inflammation that may be implicated in the development of comorbidities.......Patients with chronic obstructive pulmonary disease (COPD) have evidence of systemic inflammation that may be implicated in the development of comorbidities....

  2. Skeletal muscle regeneration is modulated by inflammation

    Directory of Open Access Journals (Sweden)

    Wenjun Yang

    2018-04-01

    Full Text Available Skeletal muscle regeneration is a complex process orchestrated by multiple steps. Recent findings indicate that inflammatory responses could play central roles in bridging initial muscle injury responses and timely muscle injury reparation. The various types of immune cells and cytokines have crucial roles in muscle regeneration process. In this review, we briefly summarise the functions of acute inflammation in muscle regeneration. The translational potential of this article: Immune system is closely relevant to the muscle regeneration. Understanding the mechanisms of inflammation in muscle regeneration is therefore critical for the development of effective regenerative, and therapeutic strategies in muscular disorders. This review provides information for muscle regeneration research regarding the effects of inflammation on muscle regeneration. Keywords: Chronic muscle disorders, Cytokines, Immune cells, Inflammation, Muscle regeneration, Muscle stem cells

  3. Cough reflex sensitivity and airway inflammation in patients with chronic cough due to non-acid gastro-oesophageal reflux.

    Science.gov (United States)

    Qiu, Zhihong; Yu, Li; Xu, Shuchang; Liu, Bo; Zhao, Ting; Lü, Hanjing; Qiu, Zhongmin

    2011-05-01

    The aim of this study was to explore the pathogenesis of chronic cough caused by non-acid reflux. Seven patients with chronic cough due to non-acid reflux, 12 patients with chronic cough due to acid reflux, 10 patients with gastro-oesophageal reflux disease without cough and 12 healthy volunteers were recruited for the study. All subjects underwent oesophageal multi-channel intraluminal impedance measurements combined with pH monitoring, and assessment of cough reflex sensitivity to capsaicin and induced sputum cytology. The concentrations of substance P, mast cell tryptase, prostaglandin D2 and histamine in induced sputum were measured by ELISA. Cough threshold C2 and C5 did not differ between patients with chronic cough due to non-acid or acid reflux, but the values were significantly lower than those for patients with gastro-oesophageal reflux disease without cough and healthy volunteers. Weakly acidic reflux episodes were obviously more frequent in patients with chronic cough due to non-acid reflux than in the other three groups. Sputum substance P and mast cell tryptase concentrations were remarkably increased in patients with chronic cough, but were similar for those with cough due to non-acid or acid reflux. There were significant inverse correlations between substance P levels and cough threshold C2 or C5 in patients with cough due to non-acid or acid reflux, and between mast cell tryptase levels and cough threshold C2 in patients with cough due to acid reflux. Chronic cough due to non-acid reflux may be related to cough reflex hypersensitivity caused by neurogenic airway inflammation and mast cell activation, in which weakly acidic reflux is possibly a major factor. © 2011 The Authors. Respirology © 2011 Asian Pacific Society of Respirology.

  4. 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.

  5. Predictors of Inflammation in a Cohort of Bolivian Infants and Toddlers

    Science.gov (United States)

    Burke, Rachel M.; Suchdev, Parminder S.; Rebolledo, Paulina A.; Fabiszewski de Aceituno, Anna M.; Revollo, Rita; Iñiguez, Volga; Klein, Mitchel; Drews-Botsch, Carolyn; Leon, Juan S.

    2016-01-01

    Inflammation has been associated with cardiovascular disease and other health outcomes in children and adults, yet few longitudinal data are available on prevalence and predictors of inflammation in infants. We aimed to identify the prevalence of inflammation in a cohort of Bolivian infants and estimate its association with acute (recent illnesses) and chronic (overweight, stunting) morbidities and potential pathogen exposure (represented by water, sanitation, and hygiene [WASH] resources). We measured plasma concentrations of two acute phase proteins (C-reactive protein [CRP], marking acute inflammation, and alpha(1)-acid-glycoprotein [AGP], marking chronic inflammation) at three time points (target 2, 6–8, and 12–18 months). Of 451 singleton infants enrolled in the parent study, 272 had the first blood draw and complete data. Anthropometry and sociodemographic and recent illness data (2-week recall of cough, diarrhea, and fever) were collected at each visit. Inflammation was defined as CRP > 5 mg/L or AGP > 1 g/L. The prevalence of inflammation increased from early infancy (3% at first blood draw) to later infancy (15–22% at later blood draws). Recent cough, recent fever, and age in months were significantly associated with relative increases in CRP (7–44%) and AGP (5–23%), whereas recent diarrhea was only significantly associated with an increase in CRP (48%). Neither anthropometry nor WASH was significantly associated with inflammation. Results confirm the role of recent acute illness in inflammation in infants, and indicate that adiposity and WASH are not as important to inflammation in this age category. PMID:27527627

  6. Chronic inflammatory cells and damaged limbal cells in pterygium ...

    African Journals Online (AJOL)

    Background: Chronic inflammation in pterygium occurrence has not been explained. Whether damaged limbal basal epithelial cells are associated with pterygium occurrence in black Africans is not clear. Objective: To explain chronic inflammation in pterygium, and to clarify whether damaged limbal basal epithelial cells ...

  7. 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

  8. [Bio-ecological control of chronic liver disease and encephalopathy].

    Science.gov (United States)

    Bengmark, S; Di Cocco, P; Clemente, K; Corona, L; Angelico, R; Manzia, T; Famulari, A; Pisani, F; Orlando, G

    2011-08-01

    Minimal encephalopathy was originally associated with chronic liver disease but is increasingly associated with most other chronic diseases and particularly with diabetes and also chronic disorders in other organs: kidneys, lungs, thyroid and with obesity. It is increasingly with dramatically increased and more or less permanent increase in systemic inflammation, most likely a result of Western lifestyle. Frequent physical exercise and intake of foods rich in vitamins, antioxidants, fibres, lactic acid bacteria etc in combination with reduction in intake of refined and processed foods is known to reduce systemic inflammation and prevent chronic diseases. Some lactic acid bacteria, especially Lb paracasei, lb plantarum and pediococcus pentosaceus have proven effective to reduce inflammation and eliminate encephalopathy. Significant reduction in blood ammonia levels and endotoxin levels were reported in parallel to improvement of liver disease. Subsequent studies with other lactic acid bacteria seem to demonstrate suppression of inflammation and one study also provides evidence of clinical improvement.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Beyond corticosteroids: future prospects in the management of inflammation in COPD

    Directory of Open Access Journals (Sweden)

    N. Roche

    2011-09-01

    Full Text Available Inflammation plays a central role in the pathophysiology of chronic obstructive pulmonary disease (COPD. Exposure to cigarette smoke induces the recruitment of inflammatory cells in the airways and stimulates innate and adaptive immune mechanisms. Airway inflammation is involved in increased bronchial wall thickness, increased bronchial smooth muscle tone, mucus hypersecretion and loss of parenchymal elastic structures. Oxidative stress impairs tissue integrity, accelerates lung ageing and reduces the efficacy of corticosteroids by decreasing levels of histone deacetylase-2. Protease–antiprotease imbalance impairs tissues and is involved in inflammatory processes. Inflammation is also present in the pulmonary artery wall and at the systemic level in COPD patients, and may be involved in COPD-associated comorbidities. Proximal airways inflammation contributes to symptoms of chronic bronchitis while distal and parenchymal inflammation relates to airflow obstruction, emphysema and hyperinflation. Basal levels of airways and systemic inflammation are increased in frequent exacerbators. Inhaled corticosteroids are much less effective in COPD than in asthma, which relates to the intrinsically poor reversibility of COPD-related airflow obstruction and to molecular mechanisms of resistance relating to oxidative stress. Ongoing research aims at developing new drugs targeting more intimately COPD-specific mechanisms of inflammation, hypersecretion and tissue destruction and repair. Among new anti-inflammatory agents, phosphodiesterase-4 inhibitors have been the first to emerge.

  11. Current concepts on oxidative/carbonyl stress, inflammation and epigenetics in pathogenesis of chronic obstructive pulmonary disease

    International Nuclear Information System (INIS)

    Yao Hongwei; Rahman, Irfan

    2011-01-01

    Chronic obstructive pulmonary disease (COPD) is a global health problem. The current therapies for COPD are poorly effective and the mainstays of pharmacotherapy are bronchodilators. A better understanding of the pathobiology of COPD is critical for the development of novel therapies. In the present review, we have discussed the roles of oxidative/aldehyde stress, inflammation/immunity, and chromatin remodeling in the pathogenesis of COPD. An imbalance of oxidants/antioxidants caused by cigarette smoke and other pollutants/biomass fuels plays an important role in the pathogenesis of COPD by regulating redox-sensitive transcription factors (e.g., NF-κB), autophagy and unfolded protein response leading to chronic lung inflammatory response. Cigarette smoke also activates canonical/alternative NF-κB pathways and their upstream kinases leading to sustained inflammatory response in lungs. Recently, epigenetic regulation has been shown to be critical for the development of COPD because the expression/activity of enzymes that regulate these epigenetic modifications have been reported to be abnormal in airways of COPD patients. Hence, the significant advances made in understanding the pathophysiology of COPD as described herein will identify novel therapeutic targets for intervention in COPD.

  12. Exploring Black-White Differences in the Relationship Between Inflammation and Timing of Menopause.

    Science.gov (United States)

    Nowakowski, Alexandra C H; Graves, Katelyn Y

    2017-06-01

    Understanding the biosocial context of menopausal timing offers insight into social and health inequalities. Prior research on inflammatory chronic conditions suggests that inflammation may predict how early women experience menopause. We explore the ability of black race to moderate the overall relationship between chronic inflammation and timing of menopause. We use data from the National Social Life, Health, and Aging Project on inflammation, age of last menstruation, and race as well as relevant social and medical covariates. We conduct event history modeling to predict age at menopause by inflammatory biomarker levels. Using interaction analysis, we investigate whether being black may shape the overall relationship between inflammation status and menopause timing. Our analyses find no significant statistical interactions between black race and inflammation in predicting menopausal onset. However, we do identify independent correlational relationships between inflammation and black race (r = 0.136) and between menopausal timing and black race (r = -0.129) as well as inflammation (r = -0.138) that emerge as significant in corresponding regression models. We conclude that race probably does not moderate associations between inflammation and menopause. Yet, we also note that the original parameter estimate for black race's impact on menopausal onset (HR = 1.29, p menopause relationship and recommend future research using mediation modeling.

  13. Homeostasis, inflammation, and disease susceptibility.

    Science.gov (United States)

    Kotas, Maya E; Medzhitov, Ruslan

    2015-02-26

    While modernization has dramatically increased lifespan, it has also witnessed the increasing prevalence of diseases such as obesity, hypertension, and type 2 diabetes. Such chronic, acquired diseases result when normal physiologic control goes awry and may thus be viewed as failures of homeostasis. However, while nearly every process in human physiology relies on homeostatic mechanisms for stability, only some have demonstrated vulnerability to dysregulation. Additionally, chronic inflammation is a common accomplice of the diseases of homeostasis, yet the basis for this connection is not fully understood. Here we review the design of homeostatic systems and discuss universal features of control circuits that operate at the cellular, tissue, and organismal levels. We suggest a framework for classification of homeostatic signals that is based on different classes of homeostatic variables they report on. Finally, we discuss how adaptability of homeostatic systems with adjustable set points creates vulnerability to dysregulation and disease. This framework highlights the fundamental parallels between homeostatic and inflammatory control mechanisms and provides a new perspective on the physiological origin of inflammation. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. 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.

  15. 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.

  16. Ionizing radiation, inflammation, and their interactions in colon carcinogenesis in Mlh1-deficient mice.

    Science.gov (United States)

    Morioka, Takamitsu; Miyoshi-Imamura, Tomoko; Blyth, Benjamin J; Kaminishi, Mutsumi; Kokubo, Toshiaki; Nishimura, Mayumi; Kito, Seiji; Tokairin, Yutaka; Tani, Shusuke; Murakami-Murofushi, Kimiko; Yoshimi, Naoki; Shimada, Yoshiya; Kakinuma, Shizuko

    2015-03-01

    Genetic, physiological and environmental factors are implicated in colorectal carcinogenesis. Mutations in the mutL homolog 1 (MLH1) gene, one of the DNA mismatch repair genes, are a main cause of hereditary colon cancer syndromes such as Lynch syndrome. Long-term chronic inflammation is also a key risk factor, responsible for colitis-associated colorectal cancer; radiation exposure is also known to increase colorectal cancer risk. Here, we studied the effects of radiation exposure on inflammation-induced colon carcinogenesis in DNA mismatch repair-proficient and repair-deficient mice. Male and female Mlh1(-/-) and Mlh1(+/+) mice were irradiated with 2 Gy X-rays when aged 2 weeks or 7 weeks and/or were treated with 1% dextran sodium sulfate (DSS) in drinking water for 7 days at 10 weeks old to induce mild inflammatory colitis. No colon tumors developed after X-rays and/or DSS treatment in Mlh1(+/+) mice. Colon tumors developed after DSS treatment alone in Mlh1(-/-) mice, and exposure to radiation prior to DSS treatment increased the number of tumors. Histologically, colon tumors in the mice resembled the subtype of well-to-moderately differentiated adenocarcinomas with tumor-infiltrating lymphocytes of human Lynch syndrome. Immunohistochemistry revealed that expression of both p53 and β-catenin and loss of p21 and adenomatosis polyposis coli proteins were observed at the later stages of carcinogenesis, suggesting a course of molecular pathogenesis distinct from typical sporadic or colitis-associated colon cancer in humans. In conclusion, radiation exposure could further increase the risk of colorectal carcinogenesis induced by inflammation under the conditions of Mlh1 deficiency. © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

  17. Anti-Inflammatory and Antinociceptive Effects of Salbutamol on Acute and Chronic Models of Inflammation in Rats: Involvement of an Antioxidant Mechanism

    Directory of Open Access Journals (Sweden)

    Hulya Uzkeser

    2012-01-01

    Full Text Available The possible role of β-2 adrenergic receptors in modulation of inflammatory and nociceptive conditions suggests that the β-2 adrenergic receptor agonist, salbutamol, may have beneficial anti-inflammatory and analgesic effects. Therefore, in this study, we induced inflammatory and nociceptive responses with carrageenan-induced paw edema or cotton-pellet-induced granuloma models, both of which result in oxidative stress. We hypothesized that salbutamol would prevent inflammatory and nociceptive responses by stimulating β-2 adrenergic receptors and the prevention of generation of ROS during the acute inflammation process in rats. Both doses of salbutamol used in the study (1 and 2 mg/kg effectively blocked the acute inflammation and inflammatory nociception induced by carrageenan. In the cotton-pellet-induced granuloma test, both doses of salbutamol also significantly decreased the weight of granuloma tissue on the cotton pellets when compared to the control. Anti-inflammatory and analgesic effects of salbutamol were found to be comparable with those of indomethacin. Salbutamol decreased myeloperoxidase (MPO activity and lipid peroxidation (LPO level and increased the activity of superoxide dismutase (SOD and level of glutathione (GSH during the acute phase of inflammation. In conclusion, salbutamol can decrease acute and chronic inflammation, possibly through the stimulation of β-2 adrenergic receptors. This anti-inflammatory effect may be of significance in asthma treatment, where inflammation also takes part in the etiopathology. This study reveals that salbutamol has significant antioxidative effects, which at least partially explain its anti-inflammatory capabilities. These findings presented here may also shed light on the roles of β-2 adrenergic receptors in inflammatory and hyperalgesic conditions.

  18. 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.

  19. Persistent low-grade inflammation and regular exercise

    DEFF Research Database (Denmark)

    Astrom, Maj-Briit; Feigh, Michael; Pedersen, Bente Klarlund

    2010-01-01

    Persistent low-grade systemic inflammation is a feature of chronic diseases such as cardiovascular disease (CVD), type 2 diabetes and dementia and evidence exists that inflammation is a causal factor in the development of insulin resistance and atherosclerosis. Regular exercise offers protection ...... diabetes and dementia. We suggest that the anti-inflammatory effects of exercise may be mediated via a long-term effect of exercise leading to a reduction in visceral fat mass and/or by induction of anti-inflammatory cytokines with each bout of exercise....

  20. Effects of omega-3 fatty acid plus alpha-tocopherol supplementation on malnutrition-inflammation score, biomarkers of inflammation and oxidative stress in chronic hemodialysis patients.

    Science.gov (United States)

    Asemi, Zatollah; Soleimani, Alireza; Shakeri, Hossein; Mazroii, Navid; Esmaillzadeh, Ahmad

    2016-11-01

    The current study was carried out to assess the effects of omega-3 fatty acid and alpha-tocopherol co-supplementation on malnutrition-inflammation score (MIS), biomarkers of inflammation and oxidative stress in chronic hemodialysis (HD) patients. In a randomized double-blind placebo-controlled clinical trial, 120 patients with chronic HD were included. Patients were randomly allocated into four groups to receive: (1) 1250 mg/day omega-3 fatty acid containing 600 mg EPA and 300 mg DHA + alpha-tocopherol placebo (n = 30); (2) 400 IU/day alpha-tocopherol + omega-3 fatty acids placebo (n = 30); (3) 1250 mg omega-3 fatty acids/day + 400 IU/day alpha-tocopherol (n = 30); and (4) omega-3 fatty acids placebo + alpha-tocopherol placebo (n = 30) for 12 weeks. After 12 weeks of intervention, all three groups of alpha-tocopherol only, individual omega-3 fatty acids, and combined omega-3 fatty acids and alpha-tocopherol experienced a significant improvements in MIS compared with the placebo group; however, improvements were much greater in the individual omega-3 fats (-1.4 ± 1.4) and combined omega-3 fats and alpha-tocopherol (-1.1 ± 2.3) groups compared with alpha-tocopherol group alone (-0.5 ± 1.7, P = 0.004). Furthermore, both individual and combined intervention with omega-3 fats and alpha-tocopherol led to a significant increase in plasma nitric oxide (NO) (combined group: +17.6 ± 29.3; alpha-tocopherol: +43.1 ± 36.3; omega-3 fats: +31.0 ± 40.0; and placebo: -0.5 ± 18.5 µmol/L, respectively, P acids and alpha-tocopherol co-supplementation for 12 weeks among HD patients improved MIS, plasma NO and TAC levels. Future studies with longer duration of the intervention are needed to confirm the validity of our findings. CLINICAL REGISTRATION: www.irct.ir as IRCT201410245623N28.

  1. The molecular imaging approach to image infections and inflammation by nuclear medicine techniques

    NARCIS (Netherlands)

    Signore, Alberto; Glaudemans, Andor W. J. M.

    2011-01-01

    Inflammatory and infectious diseases are a heterogeneous class of diseases that may be divided into infections, acute inflammation and chronic inflammation. Radiological imaging techniques have, with the exception of functional MRI, high sensitivity but lack in specificity. Nuclear medicine

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

    Directory of Open Access Journals (Sweden)

    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

  4. Chronic inflammation modulates ghrelin levels in humans and rats.

    Science.gov (United States)

    Otero, M; Nogueiras, R; Lago, F; Dieguez, C; Gomez-Reino, J J; Gualillo, O

    2004-03-01

    The aim of this work was to investigate whether changes in plasma ghrelin, the recently discovered 28-amino acid gastric hormone that regulates growth hormone (GH) secretion and energy homeostasis, occur during inflammation in adjuvant-induced arthritis (AA) in rats. For completeness, ghrelin plasma levels were measured in rheumatoid arthritis (RA) patients. AA was induced in male Lewis rats using Freund's complete adjuvant. Animals were monitored for weight and food intake, every 2 or 3 days, along all time-course experiments. Plasma ghrelin concentrations in 31 RA patients and 18 healthy controls, as well as in rats, were determined by a specific double-antibody radioimmunoassay. Gastric ghrelin mRNA expression was evaluated by northern blot analysis. Human GH and insulin-like growth factor (IGF)-1 were determined by quantitative chemiluminescence assay. Compared with controls, arthritic rats gained significantly (P Ghrelin plasma levels were significantly lower at day 7 after arthritis induction than in controls (AA 7 = 91.2 +/- 5.6 pg/ml vs controls = 124.75 +/- 5.9 pg/ml), but they recovered to control levels by day 15. RA patients had ghrelin plasma levels significantly lower than healthy controls (RA = 24.54 +/- 2.57 pg/ml vs 39.01 +/- 4.47 pg/ml of healthy controls; P = 0.0041). In AA, there is a compensatory variation of ghrelin levels that relates to body weight adjustments. Recovery of ghrelin levels in the latter stage suggests an adaptive response and may represent a compensatory mechanism under catabolic conditions. In RA patients, chronic imbalance in ghrelin levels suggests that this gastric hormone may participate, together with other factors, in alterations of metabolic status during inflammatory stress.

  5. Skeletal muscle inflammation and insulin resistance in obesity

    Science.gov (United States)

    Wu, Huaizhu; Ballantyne, Christie M.

    2017-01-01

    Obesity is associated with chronic inflammation, which contributes to insulin resistance and type 2 diabetes mellitus. Under normal conditions, skeletal muscle is responsible for the majority of insulin-stimulated whole-body glucose disposal; thus, dysregulation of skeletal muscle metabolism can strongly influence whole-body glucose homeostasis and insulin sensitivity. Increasing evidence suggests that inflammation occurs in skeletal muscle in obesity and is mainly manifested by increased immune cell infiltration and proinflammatory activation in intermyocellular and perimuscular adipose tissue. By secreting proinflammatory molecules, immune cells may induce myocyte inflammation, adversely regulate myocyte metabolism, and contribute to insulin resistance via paracrine effects. Increased influx of fatty acids and inflammatory molecules from other tissues, particularly visceral adipose tissue, can also induce muscle inflammation and negatively regulate myocyte metabolism, leading to insulin resistance. PMID:28045398

  6. Delayed expression of cell cycle proteins contributes to astroglial scar formation and chronic inflammation after rat spinal cord contusion

    Directory of Open Access Journals (Sweden)

    Wu Junfang

    2012-07-01

    Full Text Available Abstract Background Traumatic spinal cord injury (SCI induces secondary tissue damage that is associated with astrogliosis and inflammation. We previously reported that acute upregulation of a cluster of cell-cycle-related genes contributes to post-mitotic cell death and secondary damage after SCI. However, it remains unclear whether cell cycle activation continues more chronically and contributes to more delayed glial change. Here we examined expression of cell cycle-related proteins up to 4 months following SCI, as well as the effects of the selective cyclin-dependent kinase (CDKs inhibitor CR8, on astrogliosis and microglial activation in a rat SCI contusion model. Methods Adult male rats were subjected to moderate spinal cord contusion injury at T8 using a well-characterized weight-drop model. Tissue from the lesion epicenter was obtained 4 weeks or 4 months post-injury, and processed for protein expression and lesion volume. Functional recovery was assessed over the 4 months after injury. Results Immunoblot analysis demonstrated a marked continued upregulation of cell cycle-related proteins − including cyclin D1 and E, CDK4, E2F5 and PCNA − for 4 months post-injury that were highly expressed by GFAP+ astrocytes and microglia, and co-localized with inflammatory-related proteins. CR8 administrated systemically 3 h post-injury and continued for 7 days limited the sustained elevation of cell cycle proteins and immunoreactivity of GFAP, Iba-1 and p22PHOX − a key component of NADPH oxidase − up to 4 months after SCI. CR8 treatment significantly reduced lesion volume, which typically progressed in untreated animals between 1 and 4 months after trauma. Functional recovery was also significantly improved by CR8 treatment after SCI from week 2 through week 16. Conclusions These data demonstrate that cell cycle-related proteins are chronically upregulated after SCI and may contribute to astroglial scar

  7. Acute effects of cigarette smoke on inflammation and oxidative stress : a review

    NARCIS (Netherlands)

    van der Vaart, H; Postma, DS; Timens, W; Ten Hacken, NHT

    Compared with the effects of chronic smoke exposure on lung function and airway inflammation, there are few data on the acute effects of smoking. A review of the literature identified 123 studies investigating the acute effects of cigarette smoking on inflammation and oxidative stress in human,

  8. 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 < 0.001) when compared with other tertiles of MIS. ROC curve analysis of MIS showed 56.5% sensitivity and 81% specificity in predicting death rate (AUC 0.709; 95% CI 0.604-0.815, p < 0.001). Kaplan-Meier survival analysis showed MIS ≥7 had a strong association (log rank test, p < 0.001) with mortality during 36 and more months of follow-up time. In unadjusted analyses

  9. Inflammation and bone mineral density: A Mendelian randomization study

    OpenAIRE

    Huang, Jian V.; Schooling, C. Mary

    2017-01-01

    Osteoporosis is a common age-related disorder leading to an increase in osteoporotic fractures and resulting in significant suffering and disability. Inflammation may contribute to osteoporosis, as it does to many other chronic diseases. We examined whether inflammation is etiologically relevant to osteoporosis, assessed from bone mineral density (BMD), as a new potential target of intervention, or whether it is a symptom/biomarker of osteoporosis. We obtained genetic predictors of inflammato...

  10. Connecting the immune system, systemic chronic inflammation and the gut microbiome: The role of sex.

    Science.gov (United States)

    Rizzetto, Lisa; Fava, Francesca; Tuohy, Kieran M; Selmi, Carlo

    2018-05-31

    Unresolved low grade systemic inflammation represents the underlying pathological mechanism driving immune and metabolic pathways involved in autoimmune diseases (AID). Mechanistic studies in animal models of AID and observational studies in patients have found alterations in gut microbiota communities and their metabolites, suggesting a microbial contribution to the onset or progression of AID. The gut microbiota and its metabolites have been shown to influence immune functions and immune homeostasis both within the gut and systematically. Microbial derived-short chain fatty acid (SCFA) and bio-transformed bile acid (BA) have been shown to influence the immune system acting as ligands specific cell signaling receptors like GPRCs, TGR5 and FXR, or via epigenetic processes. Similarly, intestinal permeability (leaky gut) and bacterial translocation are important contributors to chronic systemic inflammation and, without repair of the intestinal barrier, might represent a continuous inflammatory stimulus capable of triggering autoimmune processes. Recent studies indicate gender-specific differences in immunity, with the gut microbiota shaping and being concomitantly shaped by the hormonal milieu governing differences between the sexes. A bi-directional cross-talk between microbiota and the endocrine system is emerging with bacteria being able to produce hormones (e.g. serotonin, dopamine and somatostatine), respond to host hormones (e.g. estrogens) and regulate host hormones' homeostasis (e.g by inhibiting gene prolactin transcription or converting glucocorticoids to androgens). We review herein how gut microbiota and its metabolites regulate immune function, intestinal permeability and possibly AID pathological processes. Further, we describe the dysbiosis within the gut microbiota observed in different AID and speculate how restoring gut microbiota composition and its regulatory metabolites by dietary intervention including prebiotics and probiotics could help in

  11. [Liesegang's rings resembling helminthiasis].

    Science.gov (United States)

    Zámecník, M; Riedl, I

    1996-12-01

    So called Liesegang's rings are lamellar corpuscles which develop after periodical precipitation of oversaturated solutions in gel medium. They can occur in cysts, closed cavities, inflammatory exudates and necroses. They resemble parasitic eggs, larvae or adult forms. A case of 28-year-old woman is presented with many Liesegang's rings in a stuff from dilated renal calyx. Their preliminary evaluation considered helminths, especially Dioctophyma renale.

  12. Inflammation: a trigger for acute coronary syndrome

    International Nuclear Information System (INIS)

    SAGER, Hendrik B.; NAHRENDORF, Matthias

    2016-01-01

    Atherosclerosis is a chronic inflammatory disease of the vessel wall and a major cause of death worldwide. One of atherosclerosis’ most dreadful complications are acute coronary syndromes that comprise ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction, and unstable angina. We now understand that inflammation substantially contributes to the initiation, progression, and destabilization of atherosclerosis. In this review, we will focus on the role of inflammatory leukocytes, which are the cellular protagonists of vascular inflammation, in triggering disease progression and, ultimately, the destabilization that causes acute coronary syndromes.

  13. Dietary Modulation of Inflammation-Induced Colorectal Cancer through PPARγ

    Directory of Open Access Journals (Sweden)

    Ashlee B. Carter

    2009-01-01

    Full Text Available Mounting evidence suggests that the risk of developing colorectal cancer (CRC is dramatically increased for patients with chronic inflammatory diseases. For instance, patients with Crohn's Disease (CD or Ulcerative Colitis (UC have a 12–20% increased risk for developing CRC. Preventive strategies utilizing nontoxic natural compounds that modulate immune responses could be successful in the suppression of inflammation-driven colorectal cancer in high-risk groups. The increase of peroxisome proliferator-activated receptor-γ (PPAR-γ expression and its transcriptional activity has been identified as a target for anti-inflammatory efforts, and the suppression of inflammation-driven colon cancer. PPARγ down-modulates inflammation and elicits antiproliferative and proapoptotic actions in epithelial cells. All of which may decrease the risk for inflammation-induced CRC. This review will focus on the use of orally active, naturally occurring chemopreventive approaches against inflammation-induced CRC that target PPARγ and therefore down-modulate inflammation.

  14. Inflammation and Immune Response in COPD: Where Do We Stand?

    Directory of Open Access Journals (Sweden)

    Nikoletta Rovina

    2013-01-01

    Full Text Available Increasing evidence indicates that chronic inflammatory and immune responses play key roles in the development and progression of COPD. Recent data provide evidence for a role in the NLRP3 inflammasome in the airway inflammation observed in COPD. Cigarette smoke activates innate immune cells by triggering pattern recognition receptors (PRRs to release “danger signal”. These signals act as ligands to Toll-like receptors (TLRs, triggering the production of cytokines and inducing innate inflammation. In smokers who develop COPD there appears to be a specific pattern of inflammation in the airways and parenchyma as a result of both innate and adaptive immune responses, with the predominance of CD8+ and CD4+ cells, and in the more severe disease, with the presence of lymphoid follicles containing B lymphocytes and T cells. Furthermore, viral and bacterial infections interfere with the chronic inflammation seen in stable COPD and exacerbations via pathogen-associated molecular patterns (PAMPs. Finally, autoimmunity is another novel aspect that may play a critical role in the pathogenesis of COPD. This review is un update of the currently discussed roles of inflammatory and immune responses in the pathogenesis of COPD.

  15. Targeting inflammation with autoantigen-specific T cells

    NARCIS (Netherlands)

    Guichelaar, T.

    2008-01-01

    Chronic autoimmune diseases are driven by cells that respond to tissue components of the body. Inflammation in diseases like rheumatoid arthritis, diabetes or multiple sclerosis, can be suppressed by drug therapy. However, the broad range of immunosuppressive action of these drugs often does not

  16. Cumulative childhood risk is associated with a new measure of chronic inflammation in adulthood.

    Science.gov (United States)

    Rasmussen, Line Jee Hartmann; Moffitt, Terrie E; Eugen-Olsen, Jesper; Belsky, Daniel W; Danese, Andrea; Harrington, HonaLee; Houts, Renate M; Poulton, Richie; Sugden, Karen; Williams, Benjamin; Caspi, Avshalom

    2018-05-09

    Childhood risk factors are associated with elevated inflammatory biomarkers in adulthood, but it is unknown whether these risk factors are associated with increased adult levels of the chronic inflammation marker soluble urokinase plasminogen activator receptor (suPAR). We aimed to test the hypothesis that childhood exposure to risk factors for adult disease is associated with elevated suPAR in adulthood and to compare suPAR with the oft-reported inflammatory biomarker C-reactive protein (CRP). Prospective study of a population-representative 1972-1973 birth cohort; the Dunedin Multidisciplinary Health and Development Study observed participants to age 38 years. Main childhood predictors were poor health, socioeconomic disadvantage, adverse childhood experiences (ACEs), low IQ, and poor self-control. Main adult outcomes were adulthood inflammation measured as suPAR and high-sensitivity CRP (hsCRP). Participants with available plasma samples at age 38 were included (N = 837, 50.5% male). suPAR (mean 2.40 ng/ml; SD 0.91) was positively correlated with hsCRP (r 0.15, p childhood risks were aggregated into a Cumulative Childhood Risk index, and controlling for sex, BMI, and smoking, Cumulative Childhood Risk was associated with higher suPAR (b 0.10; SE 0.03; p = .002). Cumulative Childhood Risk predicted elevated suPAR, after controlling for hsCRP (b 0.18; SE 0.03; p childhood risk factors was associated with higher suPAR levels, independent of CRP. suPAR is a useful addition to studies connecting childhood risk to adult inflammatory burden. © 2018 Association for Child and Adolescent Mental Health.

  17. 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.

  18. 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.

  19. 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

  20. 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

  1. 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

  2. Chronic pancreatitis.

    Science.gov (United States)

    Kleeff, Jorg; Whitcomb, David C; Shimosegawa, Tooru; Esposito, Irene; Lerch, Markus M; Gress, Thomas; Mayerle, Julia; Drewes, Asbjørn Mohr; Rebours, Vinciane; Akisik, Fatih; Muñoz, J Enrique Domínguez; Neoptolemos, John P

    2017-09-07

    Chronic pancreatitis is defined as a pathological fibro-inflammatory syndrome of the pancreas in individuals with genetic, environmental and/or other risk factors who develop persistent pathological responses to parenchymal injury or stress. Potential causes can include toxic factors (such as alcohol or smoking), metabolic abnormalities, idiopathic mechanisms, genetics, autoimmune responses and obstructive mechanisms. The pathophysiology of chronic pancreatitis is fairly complex and includes acinar cell injury, acinar stress responses, duct dysfunction, persistent or altered inflammation, and/or neuro-immune crosstalk, but these mechanisms are not completely understood. Chronic pancreatitis is characterized by ongoing inflammation of the pancreas that results in progressive loss of the endocrine and exocrine compartment owing to atrophy and/or replacement with fibrotic tissue. Functional consequences include recurrent or constant abdominal pain, diabetes mellitus (endocrine insufficiency) and maldigestion (exocrine insufficiency). Diagnosing early-stage chronic pancreatitis is challenging as changes are subtle, ill-defined and overlap those of other disorders. Later stages are characterized by variable fibrosis and calcification of the pancreatic parenchyma; dilatation, distortion and stricturing of the pancreatic ducts; pseudocysts; intrapancreatic bile duct stricturing; narrowing of the duodenum; and superior mesenteric, portal and/or splenic vein thrombosis. Treatment options comprise medical, radiological, endoscopic and surgical interventions, but evidence-based approaches are limited. This Primer highlights the major progress that has been made in understanding the pathophysiology, presentation, prevalence and management of chronic pancreatitis and its complications.

  3. [Treatment of disbacteriosis of gastroduodenal mucous microflora in mucosa inflammation, ulcer and erosion].

    Science.gov (United States)

    Chernin, V V; Chernivets, V M; Bondarenko, V M; Bazlov, S N

    2011-01-01

    To propose pharmacotherapy of disbacteriosis of gastroduodenal mucous microflora in gastroduodenal inflammation, erosion and ulcer. The study enrolled 30 healthy volunteers, 130 ulcer patients and 36 patients with chronic gastritis (27% of the latter had chronic duodenitis). In addition to general clinical examination, fibrogastroduodenoscopy, we made histological and microbiological examinations of biopsy specimens of the mucosa from different parts of the stomach and duodenum, determined sensitivity of the microflora to antibacterial drugs. We found that recurrent ulcer, chronic gastritis and duodenitis are accompanied with overgrowth of pathogenic microflora in gastric and duodenal mucosa. We developed an effective method of the treatment of gastroduodenal mucosa microflora disbacteriosis in gastroduodenal inflammation, erosion and ulcer including antibacterial, antifungal drugs and probiotics.

  4. TRPM2 Channel Aggravates CNS Inflammation and Cognitive Impairment via Activation of Microglia in Chronic Cerebral Hypoperfusion.

    Science.gov (United States)

    Miyanohara, Jun; Kakae, Masashi; Nagayasu, Kazuki; Nakagawa, Takayuki; Mori, Yasuo; Arai, Ken; Shirakawa, Hisashi; Kaneko, Shuji

    2018-04-04

    and mental disorders that are accompanied by cognitive impairment; however, the underlying mechanisms require clarification. Here, we used a chronic cerebral hypoperfusion mouse model to investigate whether TRPM2, a Ca 2+ -permeable cation channel highly expressed in immune cells, plays a destructive role in the development of chronic cerebral hypoperfusion-induced cognitive impairment, and propose a new hypothesis in which TRPM2-mediated activation of microglia, not macrophages, specifically contributes to the pathology through the aggravation of inflammatory responses. These findings shed light on the understanding of the mechanisms of chronic cerebral hypoperfusion-related inflammation, and are expected to provide a novel therapeutic molecule for cognitive impairment in CNS diseases. Copyright © 2018 the authors 0270-6474/18/383521-14$15.00/0.

  5. TRIM21is important in the early phase of inflammation in the imiquimod-induced psoriasis-like skin inflammation mode

    DEFF Research Database (Denmark)

    Nielsen, Ane Langkilde-Lauesen; Vinter, Hanne

    2017-01-01

    Psoriasis is a chronic cutaneous inflammatory disease. The immunopathogenesis is a complex interplay between T cells, dendritic cells and the epidermis in which T cells and dendritic cells maintain skin inflammation. Anti-tumour necrosis factor (anti-TNF)-α agents have been approved for therapeut...

  6. Airborne Particulate Matter Induces Nonallergic Eosinophilic Sinonasal Inflammation in Mice.

    Science.gov (United States)

    Ramanathan, Murugappan; London, Nyall R; Tharakan, Anuj; Surya, Nitya; Sussan, Thomas E; Rao, Xiaoquan; Lin, Sandra Y; Toskala, Elina; Rajagopalan, Sanjay; Biswal, Shyam

    2017-07-01

    Exposure to airborne particulate matter (PM) has been linked to aggravation of respiratory symptoms, increased risk of cardiovascular disease, and all-cause mortality. Although the health effects of PM on the lower pulmonary airway have been extensively studied, little is known regarding the impact of chronic PM exposure on the upper sinonasal airway. We sought to test the impact of chronic airborne PM exposure on the upper respiratory system in vivo. Mice were subjected, by inhalation, to concentrated fine (2.5 μm) PM 6 h/d, 5 d/wk, for 16 weeks. Mean airborne fine PM concentration was 60.92 μm/m 3 , a concentration of fine PM lower than that reported in some major global cities. Mice were then killed and analyzed for evidence of inflammation and barrier breakdown compared with control mice. Evidence of the destructive effects of chronic airborne PM on sinonasal health in vivo, including proinflammatory cytokine release, and macrophage and neutrophil inflammatory cell accumulation was observed. A significant increase in epithelial barrier dysfunction was observed, as assessed by serum albumin accumulation in nasal airway lavage fluid, as well as decreased expression of adhesion molecules, including claudin-1 and epithelial cadherin. A significant increase in eosinophilic inflammation, including increased IL-13, eotaxin-1, and eosinophil accumulation, was also observed. Collectively, although largely observational, these studies demonstrate the destructive effects of chronic airborne PM exposure on the sinonasal airway barrier disruption and nonallergic eosinophilic inflammation in mice.

  7. Soluble tumor necrosis factor receptor-1 in preterm infants with chronic lung disease.

    Science.gov (United States)

    Sato, Miho; Mori, Masaaki; Nishimaki, Shigeru; An, Hiromi; Naruto, Takuya; Sugai, Toshiyuki; Shima, Yoshio; Seki, Kazuo; Yokota, Shumpei

    2010-04-01

    It is clear that inflammation plays an important role in developing chronic lung disease in preterm infants. The purpose of the present study is to investigate changes of serum soluble tumor necrosis factor receptor-1 levels over time in infants with chronic lung disease. The serum levels of soluble tumor necrosis factor receptor-1 were measured after delivery, and at 7, 14, 21 and 28 days of age in 10 infants with chronic lung disease and in 18 infants without chronic lung disease. The serum level of soluble tumor necrosis factor receptor-1 was significantly higher in infants with chronic lung disease than in infants without chronic lung disease after delivery. The differences between these two groups remained up to 28 days of age. Prenatal inflammation with persistence into postnatal inflammation may be involved in the onset of chronic lung disease.

  8. A characterisation of low-grade inflammation and metabolic complications in HIV-infected patients

    DEFF Research Database (Denmark)

    Andersen, Ove

    2016-01-01

    that both chronic low-grade inflammation from HIV infection and treatment with HAART trigger cellular homeostatic stress responses with adverse effects on glucose metabolism. The physiological outcome is such that the total energy storage in the adipocytes is decreased, and the remaining adipocytes resist...... metabolism, the steroid synthesis pathway, the growth hormone-insulin growth factor-1 axis, and chronic changes in adipose tissue distribution. Specifically, the mechanisms by which low-grade inflammation may affect the normal stimulatory effect of insulin on glucose and fat storage are reviewed. We propose...

  9. Persistent low-grade inflammation and regular exercise

    DEFF Research Database (Denmark)

    Åström, Maj-brit; Feigh, Michael; Pedersen, Bente Klarlund

    2010-01-01

    against all of these diseases and recent evidence suggests that the protective effect of exercise may to some extent be ascribed to an anti-inflammatory effect of regular exercise. Visceral adiposity contributes to systemic inflammation and is independently associated with the occurrence of CVD, type 2...... diabetes and dementia. We suggest that the anti-inflammatory effects of exercise may be mediated via a long-term effect of exercise leading to a reduction in visceral fat mass and/or by induction of anti-inflammatory cytokines with each bout of exercise.......Persistent low-grade systemic inflammation is a feature of chronic diseases such as cardiovascular disease (CVD), type 2 diabetes and dementia and evidence exists that inflammation is a causal factor in the development of insulin resistance and atherosclerosis. Regular exercise offers protection...

  10. Nano-based theranostics for chronic obstructive lung diseases: challenges and therapeutic potential.

    Science.gov (United States)

    Vij, Neeraj

    2011-09-01

    The major challenges in the delivery and therapeutic efficacy of nano-delivery systems in chronic obstructive airway conditions are airway defense, severe inflammation and mucous hypersecretion. Chronic airway inflammation and mucous hypersecretion are hallmarks of chronic obstructive airway diseases, including asthma, COPD (chronic obstructive pulmonary disease) and CF (cystic fibrosis). Distinct etiologies drive inflammation and mucous hypersecretion in these diseases, which are further induced by infection or components of cigarette smoke. Controlling chronic inflammation is at the root of treatments such as corticosteroids, antibiotics or other available drugs, which pose the challenge of sustained delivery of drugs to target cells or tissues. In spite of the wide application of nano-based drug delivery systems, very few are tested to date. Targeted nanoparticle-mediated sustained drug delivery is required to control inflammatory cell chemotaxis, fibrosis, protease-mediated chronic emphysema and/or chronic lung obstruction in COPD. Moreover, targeted epithelial delivery is indispensable for correcting the underlying defects in CF and targeted inflammatory cell delivery for controlling other chronic inflammatory lung diseases. We propose that the design and development of nano-based targeted theranostic vehicles with therapeutic, imaging and airway-defense penetrating capability, will be invaluable for treating chronic obstructive lung diseases. This paper discusses a novel nano-theranostic strategy that we are currently evaluating to treat the underlying cause of CF and COPD lung disease.

  11. So depression is an inflammatory disease, but where does the inflammation come from?

    Science.gov (United States)

    Berk, Michael; Williams, Lana J; Jacka, Felice N; O'Neil, Adrienne; Pasco, Julie A; Moylan, Steven; Allen, Nicholas B; Stuart, Amanda L; Hayley, Amie C; Byrne, Michelle L; Maes, Michael

    2013-09-12

    We now know that depression is associated with a chronic, low-grade inflammatory response and activation of cell-mediated immunity, as well as activation of the compensatory anti-inflammatory reflex system. It is similarly accompanied by increased oxidative and nitrosative stress (O&NS), which contribute to neuroprogression in the disorder. The obvious question this poses is 'what is the source of this chronic low-grade inflammation?' This review explores the role of inflammation and oxidative and nitrosative stress as possible mediators of known environmental risk factors in depression, and discusses potential implications of these findings. A range of factors appear to increase the risk for the development of depression, and seem to be associated with systemic inflammation; these include psychosocial stressors, poor diet, physical inactivity, obesity, smoking, altered gut permeability, atopy, dental cares, sleep and vitamin D deficiency. The identification of known sources of inflammation provides support for inflammation as a mediating pathway to both risk and neuroprogression in depression. Critically, most of these factors are plastic, and potentially amenable to therapeutic and preventative interventions. Most, but not all, of the above mentioned sources of inflammation may play a role in other psychiatric disorders, such as bipolar disorder, schizophrenia, autism and post-traumatic stress disorder.

  12. TRPV1, TRPA1, and TRPM8 channels in inflammation, energy redirection, and water retention: role in chronic inflammatory diseases with an evolutionary perspective.

    Science.gov (United States)

    Straub, Rainer H

    2014-09-01

    Chronic inflammatory diseases are accompanied by a systemic response of the body, necessary to redirect energy-rich fuels to the activated immune system and to induce volume expansion. The systemic response is switched on by two major pathways: (a) circulating cytokines enter the brain, and (b) signals via sensory nerve fibers are transmitted to the brain. Concerning item b, sensory nerve terminals are equipped with a multitude of receptors that sense temperature, inflammation, osmolality, and pain. Thus, they can be important to inform the brain about peripheral inflammation. Central to these sensory modalities are transient receptor potential channels (TRP channels) on sensory nerve endings. For example, TRP vanilloid 1 (TRPV1) can be activated by heat, inflammatory factors (e.g., protons, bradykinin, anandamide), hyperosmolality, pungent irritants, and others. TRP channels are multimodal switches that transmit peripheral signals to the brain, thereby inducing a systemic response. It is demonstrated how and why these TRP channels (TRPV1, TRP ankyrin type 1 (TRPA1), and TRP melastatin type 8 (TRPM8)) are important to start up a systemic response of energy expenditure, energy allocation, and water retention and how this is linked to a continuously activated immune system in chronic inflammatory diseases.

  13. Leukocyte count, systemic inflammation, and health status in older adults: a narrative review

    Directory of Open Access Journals (Sweden)

    Chmielewski Piotr

    2018-03-01

    Full Text Available Epidemiological and clinical studies suggest that elevated leukocyte count within the normal range can predict cardiovascular and total mortality in older adults. These findings are remarkable because this simple and common laboratory test is included in routine medical check-ups. It is well known that chronic systemic inflammation (inflammaging is one of the hallmarks of aging and an important component of obesity-associated insulin resistance that can lead to type 2 diabetes and other health problems in both overweight individuals and elderly people. To understand the molecular mechanisms linking increased systemic inflammation with aging-associated diseases and elevated leukocyte counts in the elderly is to unravel the multiplicity of molecular factors and mechanisms involved in chronic low-grade systemic inflammation, the gradual accumulation of random molecular damage, age-related diseases, and the process of leukopoiesis. There are several possible mechanisms through which chronic low-grade systemic inflammation is associated with both higher leukocyte count and a greater risk of aging-associated conditions in older adults. For example, the IL-6 centric model predicts that this biomediator is involved in chronic systemic inflammation and leukopoiesis, thereby suggesting that elevated leukocyte count is a signal of poor health in older adults. Alternatively, an increase in neutrophil and monocyte counts can be a direct cause of cardiovascular events in the elderly. Interestingly, some authors assert that the predictive ability of elevated leukocyte counts with regard to cardiovascular and allcause mortality among older adults surpass the predictive value of total cholesterol. This review reports the recent findings on the links between elevated but normal leukocyte counts and the increased risks of all-cause, cardiovascular, and cancer mortality. The possible molecular mechanisms linking higher but normal leukocyte counts with increased

  14. Extended retroperitoneal necrotizing fasciitis with genital involvement, resembling fournier gangrene.

    Science.gov (United States)

    Sugimoto, Motokazu; Matsuura, Kenji; Takayama, Hiroshi; Kayo, Munefumi; Ie, Tomotsugu

    2010-10-01

    Necrotizing fasciitis is a serious infection that originates in the subcutaneous tissues. Although many reports have been published about necrotizing infections of other anatomical sites, retroperitoneal necrotizing soft tissue infection is a rare entity that has been described in only a few case reports. The etiology and clinical course of retroperitoneal necrotizing fasciitis can be variable and it is often difficult to identify the etiology of the infective process. We report a 58-year-old man with rapidly progressive, gas-producing, necrotizing inflammation in the retroperitoneum, complicated with genital involvement resembling Fournier gangrene. The patient was managed successfully by aggressive drainage, debridement, and sequential laparotomies to track and control the extensive necrosis of the retroperitoneum and perineum, in addition to systemic care to control sepsis. After his general condition stabilized, early rectosigmoid adenocarcinoma was identified and resected curatively. He remained well at follow up, six months after discharge. In retrospect, the trigger of the disease process was unclear. Although it was believed possibly to be due to the colon lesion, adenocarcinoma of the rectosigmoid colon was identified and the patient was managed successfully. Similar to necrotizing infections at other anatomical sites, early diagnosis and timely surgical intervention and systemic antimicrobial therapy are mandatory for treating patients with retroperitoneal necrotizing fasciitis.

  15. Close pathological correlations between chronic kidney disease and reproductive organ-associated abnormalities in female cotton rats.

    Science.gov (United States)

    Ichii, Osamu; Nakamura, Teppei; Irie, Takao; Kouguchi, Hirokazu; Sotozaki, Kozue; Horino, Taro; Sunden, Yuji; Elewa, Yaser Hosny Ali; Kon, Yasuhiro

    2018-03-01

    Cotton rat ( Sigmodon hispidus) is a useful experimental rodent for the study of human infectious diseases. We previously clarified that cotton rats, particularly females, developed chronic kidney disease characterized by cystic lesions, inflammation, and fibrosis. The present study investigated female-associated factors for chronic kidney disease development in cotton rats. Notably, female cotton rats developed separation of the pelvic symphysis and hypertrophy in the vaginal parts of the cervix with age, which strongly associated with pyometra. The development of pyometra closely associated with the deterioration of renal dysfunction or immunological abnormalities was indicated by blood urea nitrogen and serum creatinine or spleen weight and serum albumin/globulin ratio, respectively. These parameters for renal dysfunction and immunological abnormalities were statistically correlated. These phenotypes found in the female reproductive organs were completely inhibited by ovariectomy. Further, the female cotton rats with pyometra tended to show more severe chronic kidney disease phenotypes and immunological abnormalities than those without pyometra; these changes were inhibited in ovariectomized cotton rats. With regard to renal histopathology, cystic lesions, inflammation, and fibrosis were ameliorated by ovariectomy. Notably, the immunostaining intensity of estrogen receptor α and estrogen receptor β were weak in the healthy kidneys, but both estrogen receptors were strongly induced in the renal tubules showing cystic changes. In conclusion, the close correlations among female reproductive organ-associated abnormalities, immunological abnormalities, and renal dysfunction characterize the chronic kidney disease features of female cotton rats. Thus, the cotton rat is a unique rodent model to elucidate the pathological crosstalk between chronic kidney disease and sex-related factors. Impact statement The increasing number of elderly individuals in the overall

  16. Mathematical modelling as a proof of concept for MPNs as a human inflammation model for cancer development.

    Directory of Open Access Journals (Sweden)

    Morten Andersen

    Full Text Available The chronic Philadelphia-negative myeloproliferative neoplasms (MPNs are acquired stem cell neoplasms which ultimately may transform to acute myelogenous leukemia. Most recently, chronic inflammation has been described as an important factor for the development and progression of MPNs in the biological continuum from early cancer stage to the advanced myelofibrosis stage, the MPNs being described as "A Human Inflammation Model for Cancer Development". This novel concept has been built upon clinical, experimental, genomic, immunological and not least epidemiological studies. Only a few studies have described the development of MPNs by mathematical models, and none have addressed the role of inflammation for clonal evolution and disease progression. Herein, we aim at using mathematical modelling to substantiate the concept of chronic inflammation as an important trigger and driver of MPNs.The basics of the model describe the proliferation from stem cells to mature cells including mutations of healthy stem cells to become malignant stem cells. We include a simple inflammatory coupling coping with cell death and affecting the basic model beneath. First, we describe the system without feedbacks or regulatory interactions. Next, we introduce inflammatory feedback into the system. Finally, we include other feedbacks and regulatory interactions forming the inflammatory-MPN model. Using mathematical modeling, we add further proof to the concept that chronic inflammation may be both a trigger of clonal evolution and an important driving force for MPN disease progression. Our findings support intervention at the earliest stage of cancer development to target the malignant clone and dampen concomitant inflammation.

  17. The Effect of Serine Protease Inhibitors on Airway Inflammation in a Chronic Allergen-Induced Asthma Mouse Model

    Directory of Open Access Journals (Sweden)

    Chih-Che Lin

    2014-01-01

    Full Text Available Serine protease inhibitors reportedly attenuated airway inflammation and had antioxidant in multiorgan. However, the effects of the serine protease inhibitors nafamostat mesilate (FUT, gabexate mesilate (FOY, and ulinastatin (UTI on a long-term challenged mouse model of chronic asthma are unclear. BALB/c mice (6 mice/group were intratracheally inoculated with five doses of Dermatophagoides pteronyssinus (Der p; 50 μL, 1 mg/mL at one-week intervals. Therapeutic doses of FUT (0.0625 mg/kg, FOY (20 mg/kg, or UTI (10,000 U/kg were, respectively, injected intraperitoneally into these mice. Control mice received sterile PBS. At 3 days after the last challenge, mice were sacrificed to assess airway hyperresponsiveness (AHR, remodeling, and inflammation; lung histological features; and cytokine expression profiles. Compared with untreated controls, mice treated with FUT, FOY, and UTI had decreased AHR and goblet cell hyperplasia, decreased eosinophil and neutrophil infiltration, decreased Der p-induced IL-4 levels in serum and IL-5, IL-6, IL-13, and IL-17 levels in bronchoalveolar lavage fluid, and inhibited nuclear factor (NF-κB activity in lung tissues. The serine protease inhibitors FUT, FOY, and UTI have potential therapeutic benefits for treating asthma by downregulating Th2 cytokines and Th17 cell function and inhibiting NF-κB activation in lung tissue.

  18. Clinical laboratory markers of inflammation as determinants of chronic graft-versus-host disease activity and NIH global severity.

    Science.gov (United States)

    Grkovic, L; Baird, K; Steinberg, S M; Williams, K M; Pulanic, D; Cowen, E W; Mitchell, S A; Hakim, F T; Martires, K J; Avila, D N; Taylor, T N; Salit, R B; Rowley, S D; Zhang, D; Fowler, D H; Bishop, M R; Gress, R E; Pavletic, S Z

    2012-04-01

    Chronic graft-versus-host disease (cGVHD) remains a major cause of non-relapse morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Currently there are no accepted measures of cGVHD activity to aid in clinical management and disease staging. We analyzed clinical markers of inflammation in the sera of patients with established cGVHD and correlated those with definitions of disease activity. In all, 189 adults with cGVHD (33% moderate and 66% severe according to National Institutes of Health (NIH) global scoring) were consecutively enrolled onto a cross-sectional prospective cGVHD natural history study. At the time of evaluation, 80% were receiving systemic immunosuppression and failed a median of four prior systemic therapies (PST) for their cGVHD. Lower albumin (P<0.0001), higher C-reactive protein (P = 0.043), higher platelets (P = 0.030) and higher number of PST (P<0.0001) were associated with active disease defined as clinician's intention to intensify or alter systemic therapy due to the lack of response. Higher platelet count (P = 0.021) and higher number of PST (P<0.0001) were associated with more severe diseased defined by NIH global score. This study identified common laboratory indicators of inflammation that can serve as markers of cGVHD activity and severity.

  19. Inflammation and intracranial aneurysms: mechanisms of initiation, growth, and rupture

    Directory of Open Access Journals (Sweden)

    Peter S Amenta

    2015-06-01

    Full Text Available Outcomes following aneurysmal subarachnoid hemorrhage remain poor in many patients, despite advances in microsurgical and endovascular management. Consequently, considerable effort has been placed in determining the mechanisms of aneurysm formation, growth, and rupture. Various environmental and genetic factors are implicated as key components in the aneurysm pathogenesis. Currently, sufficient evidence exists to incriminate the inflammatory response as the common pathway leading to aneurysm generation and rupture. Central to this model is the interaction between the vessel wall and inflammatory cells. Dysfunction of the endothelium and vascular smooth muscle cells (VSMCs promotes a chronic pathological inflammatory response that progressively weakens the vessel wall. We review the literature pertaining to the cellular and chemical mechanisms of inflammation that contribute to aneurysm development. Hemodynamic stress and alterations in blood flow are discussed regarding their role in promoting chronic inflammation. Endothelial cell and VSMC dysfunction are examined concerning vascular remodeling. The contribution of inflammatory cytokines, especially tumor necrosis factor-α is illustrated. Inflammatory cell infiltration, particularly macrophage-mediated deterioration of vascular integrity, is reviewed. We discuss the inflammation as a means to determine aneurysms at greatest risk of rupture. Finally, future therapeutic implications of pharmacologic modulation of the inflammation are discussed.

  20. Clinical Causes of Inflammation in Peritoneal Dialysis Patients

    Directory of Open Access Journals (Sweden)

    Yeoungjee Cho

    2014-01-01

    Full Text Available Inflammation at both systemic and local intraperitoneal levels commonly affects peritoneal dialysis (PD patients. Interest in inflammatory markers as targets of therapeutic intervention has been considerable as they are recognised as predictors of poor clinical outcomes. However, prior to embarking on strategies to reduce inflammatory burden, it is of paramount importance to define the underlying processes that drive the chronic active inflammatory status. The present review aims to comprehensively describe clinical causes of inflammation in PD patients to which potential future strategies may be targeted.

  1. Purinergic Receptors: Key Mediators of HIV-1 infection and inflammation

    Directory of Open Access Journals (Sweden)

    Talia H Swartz

    2015-11-01

    Full Text Available Human immunodeficiency virus (HIV-1 causes a chronic infection that afflicts more than 38 million individuals worldwide. While the infection can be suppressed with potent anti-retroviral therapies, individuals infected with HIV have elevated levels of inflammation as indicated by increased T cell activation, soluble biomarkers, and associated morbidity and mortality. A single mechanism linking HIV pathogenesis to this inflammation has yet to be identified. Purinergic receptors are known to mediate inflammation and have been shown to be required for HIV-1 infection at the level of HIV-1 membrane fusion. Here we review the literature on the role of purinergic receptors in HIV-1 infection and associated inflammation and describe a role for these receptors as potential therapeutic targets.

  2. RIP3-dependent necrosis induced inflammation exacerbates atherosclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Meng, Lingjun, E-mail: menglingjun@nibs.ac.cn [College of Biological Sciences, China Agricultural University, Beijing 100094 (China); National Institute of Biological Sciences, Beijing 102206 (China); Jin, Wei [Institute for Immunology, Tsinghua University, Beijing 100084 (China); Wang, Yuhui [Institute of Cardiovascular Sciences, Health Science Center, Peking University, Beijing 100191 (China); Huang, Huanwei; Li, Jia; Zhang, Cai [National Institute of Biological Sciences, Beijing 102206 (China)

    2016-04-29

    Atherothrombotic vascular disease is already the leading cause of mortality worldwide. Atherosclerosis shares features with diseases caused by chronic inflammation. More attention should concentrates on the innate immunity effect atherosclerosis progress. RIP3 (receptor-interacting protein kinase 3) act through the transcription factor named Nr4a3 (Nuclear orphan receptors) to regulate cytokine production. Deletion RIP3 decreases IL-1α production. Injection of anti-IL-1α antibody protects against the progress of atherosclerosis in ApoE −/− mice. RIP3 as a molecular switch in necrosis, controls macrophage necrotic death caused inflammation. Inhibiting necrosis will certainly reduce atherosclerosis through limit inflammation. Necrotic cell death caused systemic inflammation exacerbated cardiovascular disease. Inhibition of necrosis may yield novel therapeutic targets for treatment in years to come. - Highlights: • RIP3 regulate the Nr4a3 to control cytokine production. • Deletion RIP3 decreases IL-1a production. • Injection anti-IL-1a antibody protects against the progress of atherosclerosis. • RIP3 controls macrophage necrotic dead caused inflammation.

  3. RIP3-dependent necrosis induced inflammation exacerbates atherosclerosis

    International Nuclear Information System (INIS)

    Meng, Lingjun; Jin, Wei; Wang, Yuhui; Huang, Huanwei; Li, Jia; Zhang, Cai

    2016-01-01

    Atherothrombotic vascular disease is already the leading cause of mortality worldwide. Atherosclerosis shares features with diseases caused by chronic inflammation. More attention should concentrates on the innate immunity effect atherosclerosis progress. RIP3 (receptor-interacting protein kinase 3) act through the transcription factor named Nr4a3 (Nuclear orphan receptors) to regulate cytokine production. Deletion RIP3 decreases IL-1α production. Injection of anti-IL-1α antibody protects against the progress of atherosclerosis in ApoE −/− mice. RIP3 as a molecular switch in necrosis, controls macrophage necrotic death caused inflammation. Inhibiting necrosis will certainly reduce atherosclerosis through limit inflammation. Necrotic cell death caused systemic inflammation exacerbated cardiovascular disease. Inhibition of necrosis may yield novel therapeutic targets for treatment in years to come. - Highlights: • RIP3 regulate the Nr4a3 to control cytokine production. • Deletion RIP3 decreases IL-1a production. • Injection anti-IL-1a antibody protects against the progress of atherosclerosis. • RIP3 controls macrophage necrotic dead caused inflammation.

  4. The role of 25-hydroxyvitamin D deficiency in promoting insulin resistance and inflammation in patients with Chronic Kidney Disease: a randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Johnson David W

    2009-12-01

    Full Text Available Abstract Background Approximately 50% of patients with stage 3 Chronic Kidney Disease are 25-hydroxyvitamin D insufficient, and this prevalence increases with falling glomerular filtration rate. Vitamin D is now recognised as having pleiotropic roles beyond bone and mineral homeostasis, with the vitamin D receptor and metabolising machinery identified in multiple tissues. Worryingly, recent observational data has highlighted an association between hypovitaminosis D and increased cardiovascular mortality, possibly mediated via vitamin D effects on insulin resistance and inflammation. The main hypothesis of this study is that oral Vitamin D supplementation will ameliorate insulin resistance in patients with Chronic Kidney Disease stage 3 when compared to placebo. Secondary hypotheses will test whether this is associated with decreased inflammation and bone/adipocyte-endocrine dysregulation. Methods/Design This study is a single-centre, double-blinded, randomised, placebo-controlled trial. Inclusion criteria include; estimated glomerular filtration rate 30-59 ml/min/1.73 m2; aged ≥18 on entry to study; and serum 25-hydroxyvitamin D levels Discussion To date, no randomised controlled trial has been performed in pre-dialysis CKD patients to study the correlation between vitamin D status with supplementation, insulin resistance and markers of adverse cardiovascular risk. We remain hopeful that cholecalciferol may be a safe intervention, with health benefits beyond those related to bone-mineral homeostasis. Trial registration Australian and New Zealand Clinical Trials Registry ACTRN12609000246280.

  5. The cardiopulmonary continuum systemic inflammation as 'common soil' of heart and lung disease

    NARCIS (Netherlands)

    Ukena, Christian; Mahfoud, Felix; Kindermann, Michael; Kindermann, Ingrid; Bals, Robert; Voors, Adriaan A.; van Veldhuisen, Dirk J.; Boehm, Michael

    2010-01-01

    Coronary artery disease (CAD), chronic heart failure (CHF) or chronic obstructive pulmonary disease (COPD) occur commonly in the presence of each other and are associated with similar systemic inflammatory reactions. Inflammation plays a central role in the pathogenesis of these diseases. C-reactive

  6. Gut microbiota, low-grade inflammation, and metabolic syndrome.

    Science.gov (United States)

    Chassaing, Benoit; Gewirtz, Andrew T

    2014-01-01

    The intestinal tract is inhabited by a large diverse community of bacteria collectively referred to as the gut microbiota. Alterations in gut microbiota composition are associated with a variety of disease states including obesity, diabetes, and inflammatory bowel disease (IBD). Transplant of microbiota from diseased persons (or mice) to germfree mice transfers some aspects of disease phenotype, indicating that altered microbiota plays a role in disease establishment and manifestation. There are myriad potential mechanisms by which alterations in gut microbiota might promote disease, including increasing energy harvest, production of toxic metabolites, and molecular mimicry of host proteins. However, our research indicates that an overarching mechanism by which an aberrant microbiota negatively impacts health is by driving chronic inflammation. More specifically, we hypothesize that the histopathologically evident gut inflammation that defines IBD is a severe but relatively rare outcome of an altered host-microbiota relationship, while a much more common consequence of such disturbances is "low-grade" inflammation characterized by elevated proinflammatory gene expression that associates with, and may promote, metabolic syndrome. In this context, a variety of chronic inflammatory diseases may stem from inability of the mucosal immune system to properly manage a stable healthy relationship with the gut microbiota. While one's ability to manage their gut microbiota is dictated in part by genetics, it can be markedly influenced by the composition of the microbiota one inherits from their early environment. Moreover, the host-microbiota relationship can be perturbed by instigator bacteria or dietary components, which may prove to play a role in promoting chronic inflammatory disease states.

  7. [The way of self-defence of the organism: inflammation].

    Science.gov (United States)

    Jakab, Lajos

    2013-08-11

    The acute and chronic constitutional reactions of the organism elicited by sterile causes and pathogenic structures threatening the soundness of the organism are surveyed by the author. It is emphasized that depending on causes which can be very different, there are various syndromes occurring in the clinical practice. On the basis of multitudiness of pathogenic factors and individual differences, the infammatory reactions are clinically, pathologically and pathobiochemically can be hugely variable. The acute inflammatory response may be sterile. It is often difficult to recognize in these processes whether the inflammation is harmful or beneficial for the organism as a whole. It is possible that the inflammatory response itself is the defending resource of the individual. The non-sterile acute inflammation is evoked by pathogenic microorganisms. The variety of clinical syndromes are explained by the high diversity of pathogenic microbes, the individualities of the defending organisms, and the natural and adaptive immunity of the organism which may be intact or possibly defective. In the latter case the inflammation itself is the disease, as a consequence of a pathological process conducted by the cortico-hypothalamo-adernal axis. The acute inflammation is a defending, preventing and repairing process, constituting an important part of the natural innate immune response. It is inseparable from the natural innate immune response, which is in close cooperation with the adaptive, specific immune response with mutual effects on each of the other. The conductor and the response reactions of the two immune responses are also the same. There are alterations in serum proteins/glycoproteins synthesized mostly by the hepatocytes. Because the concentration of almost all proteins/glycoproteins may change, the use of the discriminative term "acute phase reactant" is hardly relevant. For example, the HDL molecule is a negative "acute phase reactant". On the gound of clinical

  8. 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

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

    Science.gov (United States)

    Nemmar, Abderrahim; Karaca, Turan; Beegam, Sumaya; Yuvaraju, Priya; Yasin, Javed; Hamadi, Naserddine Kamel; Ali, Badreldin H

    2016-01-01

    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. 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. 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. Prolonged pulmonary exposure to diesel exhaust particles worsen renal oxidative stress, inflammation and DNA damage in mice with adenine-induced chronic renal failure. Our data provide biological plausibility that air

  10. 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

    Directory of Open Access Journals (Sweden)

    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

  11. n-3 Polyunsaturated Fatty Acids and Mechanisms to Mitigate Inflammatory Paracrine Signaling in Obesity-Associated Breast Cancer

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    Jennifer M. Monk

    2014-10-01

    Full Text Available Globally, the prevalence of obesity is increasing which subsequently increases the risk of the development of obesity-related chronic diseases. Low-grade chronic inflammation and dysregulated adipose tissue inflammatory mediator/adipokine secretion are well-established in obesity, and these factors increase the risk of developing inflammation-associated cancer. Breast cancer is of particular interest given that increased inflammation within the subcutaneous mammary adipose tissue depot can alter the local tissue inflammatory microenvironment such that it resembles that of obese visceral adipose tissue. Therefore, in obese women with breast cancer, increased inflammatory mediators both locally and systemically can perpetuate inflammation-associated pro-carcinogenic signaling pathways, thereby increasing disease severity. Herein, we discuss some of these inflammation-associated pro-carcinogenic mechanisms of the combined obese breast cancer phenotype and offer evidence that dietary long chain n-3 polyunsaturated fatty acids (PUFA may have utility in mitigating the severity of obesity-associated inflammation and breast cancer.

  12. Bystander chronic infection negatively impacts development of CD8+ T cell memory

    Science.gov (United States)

    Stelekati, Erietta; Shin, Haina; Doering, Travis A.; Dolfi, Douglas V.; Ziegler, Carly G.; Beiting, Daniel P.; Dawson, Lucas; Liboon, Jennifer; Wolski, David; Ali, Mohammed-Alkhatim A.; Katsikis, Peter D.; Shen, Hao; Roos, David S.; Haining, W. Nicholas; Lauer, Georg M.; Wherry, E. John

    2014-01-01

    Summary Epidemiological evidence suggests that chronic infections impair immune responses to unrelated pathogens and vaccines. The underlying mechanisms, however, are unclear and distinguishing effects on priming versus development of immunological memory has been challenging. We investigated whether bystander chronic infections impact differentiation of memory CD8+ T cells, the hallmark of protective immunity against intracellular pathogens. Chronic bystander infections impaired development of memory CD8+ T cells in several mouse models and humans. These effects were independent of initial priming and were associated with chronic inflammatory signatures. Chronic inflammation negatively impacted the number of bystander CD8+ T cells and their memory development. Distinct underlying mechanisms of altered survival and differentiation were revealed with the latter regulated by the transcription factors T-bet and Blimp-1. Thus, exposure to prolonged bystander inflammation impairs the effector to memory transition. These data have relevance for immunity and vaccination during persisting infections and chronic inflammation. PMID:24837104

  13. Mechanistic Perspectives of Maslinic Acid in Targeting Inflammation

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    Wei Hsum Yap

    2015-01-01

    Full Text Available Chronic inflammation drives the development of various pathological diseases such as rheumatoid arthritis, atherosclerosis, multiple sclerosis, and cancer. The arachidonic acid pathway represents one of the major mechanisms for inflammation. Prostaglandins (PGs are lipid products generated from arachidonic acid by the action of cyclooxygenase (COX enzymes and their activity is blocked by nonsteroidal anti-inflammatory drugs (NSAIDS. The use of natural compounds in regulation of COX activity/prostaglandins production is receiving increasing attention. In Mediterranean diet, olive oil and table olives contain significant dietary sources of maslinic acid. Maslinic acid is arising as a safe and novel natural pentacyclic triterpene which has protective effects against chronic inflammatory diseases in various in vivo and in vitro experimental models. Understanding the anti-inflammatory mechanism of maslinic acid is crucial for its development as a potential dietary nutraceutical. This review focuses on the mechanistic action of maslinic acid in regulating the inflammation pathways through modulation of the arachidonic acid metabolism including the nuclear factor-kappa B (NF-κB/COX-2 expression, upstream protein kinase signaling, and phospholipase A2 enzyme activity. Further investigations may provide insight into the mechanism of maslinic acid in regulating the molecular targets and their associated pathways in response to specific inflammatory stimuli.

  14. The High Costs of Low-Grade Inflammation: Persistent Fatigue as a Consequence of Reduced Cellular-Energy Availability and Non-adaptive Energy Expenditure.

    Science.gov (United States)

    Lacourt, Tamara E; Vichaya, Elisabeth G; Chiu, Gabriel S; Dantzer, Robert; Heijnen, Cobi J

    2018-01-01

    Chronic or persistent fatigue is a common, debilitating symptom of several diseases. Persistent fatigue has been associated with low-grade inflammation in several models of fatigue, including cancer-related fatigue and chronic fatigue syndrome. However, it is unclear how low-grade inflammation leads to the experience of fatigue. We here propose a model of an imbalance in energy availability and energy expenditure as a consequence of low-grade inflammation. In this narrative review, we discuss how chronic low-grade inflammation can lead to reduced cellular-energy availability. Low-grade inflammation induces a metabolic switch from energy-efficient oxidative phosphorylation to fast-acting, but less efficient, aerobic glycolytic energy production; increases reactive oxygen species; and reduces insulin sensitivity. These effects result in reduced glucose availability and, thereby, reduced cellular energy. In addition, emerging evidence suggests that chronic low-grade inflammation is associated with increased willingness to exert effort under specific circumstances. Circadian-rhythm changes and sleep disturbances might mediate the effects of inflammation on cellular-energy availability and non-adaptive energy expenditure. In the second part of the review, we present evidence for these metabolic pathways in models of persistent fatigue, focusing on chronic fatigue syndrome and cancer-related fatigue. Most evidence for reduced cellular-energy availability in relation to fatigue comes from studies on chronic fatigue syndrome. While the mechanistic evidence from the cancer-related fatigue literature is still limited, the sparse results point to reduced cellular-energy availability as well. There is also mounting evidence that behavioral-energy expenditure exceeds the reduced cellular-energy availability in patients with persistent fatigue. This suggests that an inability to adjust energy expenditure to available resources might be one mechanism underlying persistent fatigue.

  15. The 2009 stock conference report: inflammation, obesity and metabolic disease.

    Science.gov (United States)

    Hevener, A L; Febbraio, M A

    2010-09-01

    Obesity is linked with many deleterious health consequences and is associated with increased risk of chronic disease including type 2 diabetes, atherosclerosis and certain forms of cancer. Recent work has highlighted the impact of obesity to activate inflammatory gene networks and suggests a causal function of inflammation in the pathogenesis of the metabolic syndrome. Since 2005, when Dr Gokhan Hotamisligil chaired the fourth Stock Conference in Istanbul, Turkey, entitled 'Obesity and Inflammation', there has been an explosion of studies investigating the relationship between obesity, inflammation and substrate metabolism. The exuberance surrounding this field of research is exemplified by the body of work that has been published in these past 4 years, including over 1400 publications. During this time, several novel mechanisms relating to cellular inflammation have been uncovered including the role of the hematopoietic system, toll-like receptor activation, endoplasmic reticulum stress and very recently T-cell activation in obesity-induced insulin resistance. These discoveries have led us to rethink cellular nutrient sensing and its role in inflammation and metabolic disease. Despite burgeoning investigation in this field, there still remain a number of unanswered questions. This review that evolved from the 2009 Stock Conference summarizes current research and identifies the deficiencies in our understanding of this topic. The overall goal of this Stock Conference was to bring together leading investigators in the field of inflammation and obesity research in the hope of fostering new ideas, thus advancing the pursuit of novel therapeutic strategies to reduce disease risk and or better treat chronic disease including type 2 diabetes, cardiovascular disease and cancer. © 2009 The Authors. obesity reviews © 2009 International Association for the Study of Obesity.

  16. Treatment with non-selective beta blockers is associated with reduced severity of systemic inflammation and improved survival of patients with acute-on-chronic liver failure

    DEFF Research Database (Denmark)

    Mookerjee, Rajeshwar P; Pavesi, Marco; Thomsen, Karen Louise

    2016-01-01

    BACKGROUND & AIMS: Non-selective beta blockers (NSBBs) have been shown to have deleterious outcomes in patients with refractory ascites, alcoholic hepatitis and spontaneous bacterial peritonitis leading many physicians to stop the drug in these cases. Acute-on-chronic liver failure (ACLF......) is characterized by systemic inflammation and high mortality. As NSBBs may have beneficial effects on gut motility and permeability and, systemic inflammation, the aims of this prospective, observational study were to determine whether ongoing use of NSBBs reduced 28-day mortality in ACLF patients. METHODS...... at enrollment significantly associated with treatment and mortality were taken into account as potential confounders to adjust for treatment effect. A logistic regression model was fitted. RESULTS: 164 (47%) ACLF patients received NSBBs whereas 185 patients did not. Although the CLIF-C ACLF scores were similar...

  17. HIF1α deficiency reduces inflammation in a mouse model of proximal colon cancer

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    Dessislava N. Mladenova

    2015-09-01

    Full Text Available Hypoxia-inducible factor 1α (HIF1α is a transcription factor that regulates the adaptation of cells to hypoxic microenvironments, for example inside solid tumours. Stabilisation of HIF1α can also occur in normoxic conditions in inflamed tissue or as a result of inactivating mutations in negative regulators of HIF1α. Aberrant overexpression of HIF1α in many different cancers has led to intensive efforts to develop HIF1α-targeted therapies. However, the role of HIF1α is still poorly understood in chronic inflammation that predisposes the colon to carcinogenesis. We have previously reported that the transcription of HIF1α is upregulated and that the protein is stabilised in inflammatory lesions that are caused by the non-steroidal anti-inflammatory drug (NSAID sulindac in the mouse proximal colon. Here, we exploited this side effect of long-term sulindac administration to analyse the role of HIF1α in colon inflammation using mice with a Villin-Cre-induced deletion of Hif1α exon 2 in the intestinal epithelium (Hif1αΔIEC. We also analysed the effect of sulindac sulfide on the aryl hydrocarbon receptor (AHR pathway in vitro in colon cancer cells. Most sulindac-treated mice developed visible lesions, resembling the appearance of flat adenomas in the human colon, surrounded by macroscopically normal mucosa. Hif1αΔIEC mice still developed lesions but they were smaller than in the Hif1α-floxed siblings (Hif1αF/F. Microscopically, Hif1αΔIEC mice had significantly less severe colon inflammation than Hif1αF/F mice. Molecular analysis showed reduced MIF expression and increased E-cadherin mRNA expression in the colon of sulindac-treated Hif1αΔIEC mice. However, immunohistochemistry analysis revealed a defect of E-cadherin protein expression in sulindac-treated Hif1αΔIEC mice. Sulindac sulfide treatment in vitro upregulated Hif1α, c-JUN and IL8 expression through the AHR pathway. Taken together, HIF1α expression augments inflammation

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. [Control of asthma symptoms and cellular markers of inflammation in induced sputum in children and adolescents with chronic asthma].

    Science.gov (United States)

    Ciółkowski, Janusz; Stasiowska, Barbara; Mazurek, Henryk

    2009-03-01

    After the GINA 2006 publication, asthma therapy is based on control of symptoms. However there are suggestions of monitoring of airway inflammation. Aim of the study was to compare clinical criteria of asthma control with cellular markers of lower airway inflammation in induced sputum in a group of young asthmatics. To assess relationship between sputum eosinophilia, asthma severity and spirometry. A group of 154 young patients with chronic asthma (8-21 years) underwent sputum induction by inhalation of 4,5% saline solution. Sputum induction was effective in 121 patients (78%), and in this group control of clinical symptoms was assessed according to GINA 2006 criteria. Asthma was controlled in 82 subjects (67.8%) and uncontrolled in 39 (32.2%). Patients with controlled asthma had higher FEV1/FVC (79.8 +/- 7.1% vs 74.2 +/- 9.9%; p = 0.004) and MMEF (80.7 +/- 23.0% vs 65.3 +/- 21.8%; p 3%) was observed in 24.4% of patients with controlled asthma and in 61.5% with uncontrolled asthma (p astma than in patients with moderate-severe disease (3.1 +/- 5.7% vs 7.1% +/- 8.8; p = 0.006). Patients with high sputum eosinophil count had lower FEV1 (89.4 +/- 14.9% vs 94.9 +/- 13.9%; p = 0.047), FEV1/FVC (74.5 +/- 10.1% vs 79.2 +/- 9.3%; p = 0.01) and MMEF (68.7 +/- 23.3% vs 81.7 +/- 23.1%; p = 0.004). In this study of young asthmatics, control of asthma symptoms was observed in 67.8% of patients. However, cellular markers of lower airway inflammation were present in 1/4 of patients with controlled asthma and in 3/4 with uncontrolled disease. Sputum eosinophilia was related to asthma severity. FEV1/FVC and MMEF were more important that FEV1 for estimating control of asthma. Improvement of asthma control scoring is needed as well as availability of simple methods of inflammation monitoring.

  3. 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

  4. The Effects of Resveratrol on Inflammation and Oxidative Stress in a Rat Model of Chronic Obstructive Pulmonary Disease.

    Science.gov (United States)

    Wang, Xiao-Li; Li, Ting; Li, Ji-Hong; Miao, Shu-Ying; Xiao, Xian-Zhong

    2017-09-12

    Oxidative stress and inflammation are hypothesized to contribute to the pathogenesis of chronic obstructive pulmonary disease (COPD). Resveratrol (trans-3,5,4'-trihydroxystilbene) is known for its antioxidant and anti-inflammatory properties. The study aimed to investigate the effects of resveratrol in a rat model with COPD on the regulation of oxidative stress and inflammation via the activation of Sirtuin1 (SIRTl) and proliferator-activated receptor-γ coactivator-1α (PGC-1α). Thirty Wistar rats were randomly divided into three groups: control group, COPD group and resveratrol intervention group. The COPD model was established by instilling with lipopolysaccharide (LPS) and challenging with cigarette smoke (CS). The levels of interleukin-6 (IL-6) and interleukin-8 (IL-8) in serum were measured. The levels of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) were measured. The expression levels of SIRT1 and PGC-1α in the lung tissues were examined by immunohistochemistry as well as real-time reverse transcriptase polymerase chain reaction (real-time RT-PCR) and western blotting analysis. After the treatment with resveratrol (50 mg/kg), compared with the COPD group, alleviation of inflammation and reconstruction in the small airways of the lungs were seen. Resveratrol might be correlated not only with the lower level of MDA and the higher activity of SOD, but also with the upregulation of SIRT1 and PGC-1α expression. Resveratrol treatment decreased serum levels of IL-6 and IL-8. Our findings indicate that resveratrol had a therapeutic effect in our rat COPD model, which is related to the inhibition of oxidative stress and inflammatory response. The mechanism may be related to the activation and upgrading of the SIRT1/PGC-1α signaling pathways. Thus resveratrol might be a therapeutic modality in COPD.

  5. Olive oil bioactives protect pigs against experimentally-induced chronic inflammation independently of alterations in gut microbiota.

    Directory of Open Access Journals (Sweden)

    Martin Liehr

    Full Text Available Subclinical chronic inflammation (SCI is associated with impaired animal growth. Previous work has demonstrated that olive-derived plant bioactives exhibit anti-inflammatory properties that could possibly counteract the growth-depressing effects of SCI. To test this hypothesis and define the underlying mechanism, we conducted a 30-day study in which piglets fed an olive-oil bioactive extract (OBE and their control counterparts (C+ were injected repeatedly during the last 10 days of the study with increasing doses of Escherichia coli lipopolysaccharides (LPS to induce SCI. A third group of piglets remained untreated throughout the study and served as a negative control (C-. In C+ pigs, SCI increased the circulating concentration of interleukin 1 beta (p < 0.001 and decreased feed ingestion (p < 0.05 and weight gain (p < 0.05. These responses were not observed in OBE animals. Although intestinal inflammation and colonic microbial ecology was not altered by treatments, OBE enhanced ileal mRNA abundance of tight and adherens junctional proteins (p < 0.05 and plasma recovery of mannitol (p < 0.05 compared with C+ and C-. In line with these findings, OBE improved transepithelial electrical resistance (p < 0.01 in TNF-α-challenged Caco-2/TC-7 cells, and repressed the production of inflammatory cytokines (p < 0.05 in LPS-stimulated macrophages. In summary, this work demonstrates that OBE attenuates the suppressing effect of SCI on animal growth through a mechanism that appears to involve improvements in intestinal integrity unrelated to alterations in gut microbial ecology and function.

  6. Ageing: From inflammation to cancer

    OpenAIRE

    Leonardi, G.; Accardi, G.; Monastero, R.; Nicoletti, F.; Libra, M.

    2018-01-01

    Ageing is the major risk factor for cancer development. Hallmark of the ageing process is represented by inflammaging, which is a chronic and systemic low-grade inflammatory process. Inflammation is also a hallmark of cancer and is widely recognized to influence all cancer stages from cell transformation to metastasis. Therefore, inflammaging may represent the biological phenomena able to couple ageing process with cancer development. Here we review the molecular and cellular pathway involved...

  7. 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.

  8. 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

  9. C-reactive protein and other markers of inflammation in hemodialysis patients

    Science.gov (United States)

    Heidari, Behzad

    2013-01-01

    Hemodialysis patients are at greater risk of cardiovascular disease. Higher than expected cardiovascular morbidity and mortality in this population has been attributed to dislipidemia as well as inflammation. The causes of inflammation in hemodialysis patients are multifactorial. Several markers were used for the detection of inflammatory reaction in patients with chronic renal disease. These markers can be used for the prediction of future cardiovascular events. Among the several parameters of inflammatory markers, serum, CRP is well known and its advantages for the detection of inflammation and its predictor ability has been evaluated in several studies. This review addressed the associated factors and markers of inflammation in hemodialysis patients. In addition, their ability in predicting future atherosclerosis and effect of treatment has been reviewed. However, this context particularly in using CRP as a prediction marker of inflammation and morbidity requires further studies. PMID:24009946

  10. C-reactive protein and other markers of inflammation in hemodialysis patients.

    Science.gov (United States)

    Heidari, Behzad

    2013-01-01

    Hemodialysis patients are at greater risk of cardiovascular disease. Higher than expected cardiovascular morbidity and mortality in this population has been attributed to dislipidemia as well as inflammation. The causes of inflammation in hemodialysis patients are multifactorial. Several markers were used for the detection of inflammatory reaction in patients with chronic renal disease. These markers can be used for the prediction of future cardiovascular events. Among the several parameters of inflammatory markers, serum, CRP is well known and its advantages for the detection of inflammation and its predictor ability has been evaluated in several studies. This review addressed the associated factors and markers of inflammation in hemodialysis patients. In addition, their ability in predicting future atherosclerosis and effect of treatment has been reviewed. However, this context particularly in using CRP as a prediction marker of inflammation and morbidity requires further studies.

  11. 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...

  12. The role of Toll-like receptor 2 in inflammation and fibrosis during progressive renal injury.

    Directory of Open Access Journals (Sweden)

    Jaklien C Leemans

    Full Text Available Tissue fibrosis and chronic inflammation are common causes of progressive organ damage, including progressive renal disease, leading to loss of physiological functions. Recently, it was shown that Toll-like receptor 2 (TLR2 is expressed in the kidney and activated by endogenous danger signals. The expression and function of TLR2 during renal fibrosis and chronic inflammation has however not yet been elucidated. Therefore, we studied TLR2 expression in human and murine progressive renal diseases and explored its role by inducing obstructive nephropathy in TLR2(-/- or TLR2(+/+ mice. We found that TLR2 is markedly upregulated on tubular and tubulointerstitial cells in patients with chronic renal injury. In mice with obstructive nephropathy, renal injury was associated with a marked upregulation and change in distribution of TLR2 and upregulation of murine TLR2 danger ligands Gp96, biglycan, and HMGB1. Notably, TLR2 enhanced inflammation as reflected by a significantly reduced influx of neutrophils and production of chemokines and TGF-beta in kidneys of TLR2(-/- mice compared with TLR2(+/+ animals. Although, the obstructed kidneys of TLR2(-/- mice had less interstitial myofibroblasts in the later phase of obstructive nephropathy, tubular injury and renal matrix accumulation was similar in both mouse strains. Together, these data demonstrate that TLR2 can initiate renal inflammation during progressive renal injury and that the absence of TLR2 does not affect the development of chronic renal injury and fibrosis.

  13. The management of acute and chronic pancreatitis.

    Science.gov (United States)

    Banks, Peter A; Conwell, Darwin L; Toskes, Phillip P

    2010-02-01

    Pancreatitis, which is most generally described as any inflammation of the pancreas, is a serious condition that manifests in either acute or chronic forms. Chronic pancreatitis results from irreversible scarring of the pancreas, resulting from prolonged inflammation. Six major etiologies for chronic pancreatitis have been identified: toxic/ metabolic, idiopathic, genetic, autoimmune, recurrent and severe acute pancreatitis, and obstruction. The most common symptom associated with chronic pancreatitis is pain localized to the upper-to-middle abdomen, along with food malabsorption, and eventual development of diabetes. Treatment strategies for acute pancreatitis include fasting and short-term intravenous feeding, fluid therapy, and pain management with narcotics for severe pain or nonsteroidal anti-inflammatories for milder cases. Patients with chronic disease and symptoms require further care to address digestive issues and the possible development of diabetes. Dietary restrictions are recommended, along with enzyme replacement and vitamin supplementation. More definitive outcomes may be achieved with surgical or endoscopic methods, depending on the role of the pancreatic ducts in the manifestation of disease.

  14. Autoreactive T Cells and Chronic Fungal Infection Drive Esophageal Carcinogenesis

    Science.gov (United States)

    Zhu, Feng; Willette-Brown, Jami; Song, Na-Young; Lomada, Dakshayani; Song, Yongmei; Xue, Liyan; Gray, Zane; Zhao, Zitong; Davis, Sean R.; Sun, Zhonghe; Zhang, Peilin; Wu, Xiaolin; Zhan, Qimin; Richie, Ellen R.; Hu, Yinling

    2018-01-01

    SUMMARY Humans with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), a T cell–driven autoimmune disease caused by impaired central tolerance, are susceptible to developing chronic fungal infection and esophageal squamous cell carcinoma (ESCC). However, the relationship between autoreactive T cells and chronic fungal infection in ESCC development remains unclear. We find that kinase-dead Ikkα knockin mice develop phenotypes reminiscent of APECED, including impaired central tolerance, autoreactive T cells, chronic fungal infection, and ESCCs expressing specific human ESCC markers. Using this model, we investigated the potential link between ESCC and fungal infection. Autoreactive CD4 T cells permit fungal infection and incite tissue injury and inflammation. Antifungal treatment or depletion of autoreactive CD4 T cells rescues, whereas oral fungal administration promotes, ESCC development. Inhibition of inflammation or EGFR activity decreases fungal burden. Importantly, fungal infection is highly associated with ESCCs in non-autoimmune human patients. Therefore, autoreactive T cells and chronic fungal infection, fostered by inflammation and epithelial injury, promote ESCC development. PMID:28407484

  15. 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

  16. Effects of inflammation on stem cells: together they strive?

    Science.gov (United States)

    Kizil, Caghan; Kyritsis, Nikos; Brand, Michael

    2015-04-01

    Inflammation entails a complex set of defense mechanisms acting in concert to restore the homeostatic balance in organisms after damage or pathogen invasion. This immune response consists of the activity of various immune cells in a highly complex manner. Inflammation is a double-edged sword as it is reported to have both detrimental and beneficial consequences. In this review, we discuss the effects of inflammation on stem cell activity, focusing primarily on neural stem/progenitor cells in mammals and zebrafish. We also give a brief overview of the effects of inflammation on other stem cell compartments, exemplifying the positive and negative role of inflammation on stemness. The majority of the chronic diseases involve an unremitting phase of inflammation due to improper resolution of the initial pro-inflammatory response that impinges on the stem cell behavior. Thus, understanding the mechanisms of crosstalk between the inflammatory milieu and tissue-resident stem cells is an important basis for clinical efforts. Not only is it important to understand the effect of inflammation on stem cell activity for further defining the etiology of the diseases, but also better mechanistic understanding is essential to design regenerative therapies that aim at micromanipulating the inflammatory milieu to offset the negative effects and maximize the beneficial outcomes. © 2015 The Authors.

  17. Detecting analogical resemblance without retrieving the source analogy.

    Science.gov (United States)

    Kostic, Bogdan; Cleary, Anne M; Severin, Kaye; Miller, Samuel W

    2010-06-01

    We examined whether people can detect analogical resemblance to an earlier experimental episode without being able to recall the experimental source of the analogical resemblance. We used four-word analogies (e.g., robin-nest/beaver-dam), in a variation of the recognition-without-cued-recall method (Cleary, 2004). Participants studied word pairs (e.g., robin-nest) and were shown new word pairs at test, half of which analogically related to studied word pairs (e.g., beaver-dam) and half of which did not. For each test pair, participants first attempted to recall an analogically similar pair from the study list. Then, regardless of whether successful recall occurred, participants were prompted to rate the familiarity of the test pair, which was said to indicate the likelihood that a pair that was analogically similar to the test pair had been studied. Across three experiments, participants demonstrated an ability to detect analogical resemblance without recalling the source analogy. Findings are discussed in terms of their potential relevance to the study of analogical reasoning and insight, as well as to the study of familiarity and recognition memory.

  18. Chronic inflammatory diseases are stimulated by current lifestyle: how diet, stress levels and medication prevent our body from recovering

    Directory of Open Access Journals (Sweden)

    Bosma-den Boer Margarethe M

    2012-04-01

    Full Text Available Abstract Serhan and colleagues introduced the term "Resoleomics" in 1996 as the process of inflammation resolution. The major discovery of Serhan's work is that onset to conclusion of an inflammation is a controlled process of the immune system (IS and not simply the consequence of an extinguished or "exhausted" immune reaction. Resoleomics can be considered as the evolutionary mechanism of restoring homeostatic balances after injury, inflammation and infection. Under normal circumstances, Resoleomics should be able to conclude inflammatory responses. Considering the modern pandemic increase of chronic medical and psychiatric illnesses involving chronic inflammation, it has become apparent that Resoleomics is not fulfilling its potential resolving capacity. We suggest that recent drastic changes in lifestyle, including diet and psycho-emotional stress, are responsible for inflammation and for disturbances in Resoleomics. In addition, current interventions, like chronic use of anti-inflammatory medication, suppress Resoleomics. These new lifestyle factors, including the use of medication, should be considered health hazards, as they are capable of long-term or chronic activation of the central stress axes. The IS is designed to produce solutions for fast, intensive hazards, not to cope with long-term, chronic stimulation. The never-ending stress factors of recent lifestyle changes have pushed the IS and the central stress system into a constant state of activity, leading to chronically unresolved inflammation and increased vulnerability for chronic disease. Our hypothesis is that modern diet, increased psycho-emotional stress and chronic use of anti-inflammatory medication disrupt the natural process of inflammation resolution ie Resoleomics.

  19. Role of eosinophils in airway inflammation of chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Tashkin DP

    2018-01-01

    Full Text Available Donald P Tashkin,1 Michael E Wechsler2 1Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; 2Department of Medicine, National Jewish Health, Denver, CO, USA Abstract: COPD is a significant cause of morbidity and mortality. In some patients with COPD, eosinophils contribute to inflammation that promotes airway obstruction; approximately a third of stable COPD patients have evidence of eosinophilic inflammation. Although the eosinophil threshold associated with clinical relevance in patients with COPD is currently subject to debate, eosinophil counts hold potential as biomarkers to guide therapy. In particular, eosinophil counts may be useful in assessing which patients may benefit from inhaled corticosteroid therapy, particularly regarding exacerbation prevention. In addition, several therapies targeting eosinophilic inflammation are available or in development, including monoclonal antibodies targeting the IL5 ligand, the IL5 receptor, IL4, and IL13. The goal of this review was to describe the biologic characteristics of eosinophils, their role in COPD during exacerbations and stable disease, and their use as biomarkers to aid treatment decisions. We also propose an algorithm for inhaled corticosteroid use, taking into consideration eosinophil counts and pneumonia history, and emerging eosinophil-targeted therapies in COPD. Keywords: lung disease, pulmonary diseases, corticosteroids, asthma, pneumonia

  20. Pharmacological inhibition of myostatin suppresses systemic inflammation and muscle atrophy in mice with chronic kidney disease

    Science.gov (United States)

    Zhang, Liping; Rajan, Vik; Lin, Eugene; Hu, Zhaoyong; Han, H. Q.; Zhou, Xiaolan; Song, Yanping; Min, Hosung; Wang, Xiaonan; Du, Jie; Mitch, William E.

    2011-01-01

    Chronic kidney disease (CKD) and several other catabolic conditions are characterized by increased circulating inflammatory cytokines, defects in IGF-1 signaling, abnormal muscle protein metabolism, and progressive muscle atrophy. In these conditions, no reliable treatments successfully block the development of muscle atrophy. In mice with CKD, we found a 2- to 3-fold increase in myostatin expression in muscle. Its pharmacological inhibition by subcutaneous injections of an anti-myostatin peptibody into CKD mice (IC50 ∼1.2 nM) reversed the loss of body weight (≈5–7% increase in body mass) and muscle mass (∼10% increase in muscle mass) and suppressed circulating inflammatory cytokines vs. results from CKD mice injected with PBS. Pharmacological myostatin inhibition also decreased the rate of protein degradation (16.38±1.29%; Pmyostatin expression via a NF-κB-dependent pathway, whereas muscle cells exposed to myostatin stimulated IL-6 production via p38 MAPK and MEK1 pathways. Because IL-6 stimulates muscle protein breakdown, we conclude that CKD increases myostatin through cytokine-activated pathways, leading to muscle atrophy. Myostatin antagonism might become a therapeutic strategy for improving muscle growth in CKD and other conditions with similar characteristics.—Zhang, L., Rajan, V., Lin, E., Hu, Z., Han, H.Q., Zhou, X., Song, Y., Min, H., Wang, X., Du, J., Mitch, W. E. Pharmacological inhibition of myostatin suppresses systemic inflammation and muscle atrophy in mice with chronic kidney disease. PMID:21282204

  1. Value of apparent diffusion coefficient calculation before and after gustatory stimulation in the diagnosis of acute or chronic parotitis

    Energy Technology Data Exchange (ETDEWEB)

    Ries, T.; Arndt, C.; Regier, M.; Cramer, M.C.; Adam, G.; Habermann, C.R. [Diagnostic Center, Department of Diagnostic and Interventional Radiology, Hamburg (Germany); Graessner, J. [Medical Solutions Hamburg, Siemens AG, Hamburg (Germany); Reitmeier, F.; Jaehne, M. [University Medical Center Hamburg-Eppendorf, Center of Head Care and Dermatology, Department of Otorhinolaryngology, Hamburg (Germany)

    2008-10-15

    The purpose of the study was to investigate the value of diffusion-weighted (DW) echo-planar imaging (EPI) for quantifying physiological changes of the parotid gland before and after gustatory stimulation in patients suffering from acute or chronic recurrent inflammation in comparison with healthy volunteers. Using a DW-EPI sequence at 1.5 T, parotid glands of 19 consecutive patients with acute (n = 14) and chronic (n=) inflammation of parotid glands and 52 healthy volunteers were examined. Magnetic-resonance (MR) images were obtained before and after gustatory stimulation with 5 cc of lemon juice. In volunteers mean ADC values of 1.14 x 10{sup -3} mm{sup 2}/s before and 1.2 x 10{sup -3} mm{sup 2}/s after gustatory stimulation were observed. In acute inflammation ADC values were higher before [1.22 x 10{sup -3} mm{sup 2}/s (p = 0.006)] and after stimulation [1.32 x 10{sup -3} mm{sup 2}/s (p<0.001)]. Before stimulation ADC differences between chronic inflammation (1.05 x 10{sup -3} mm{sup 2}/s) and healthy volunteers (p = 0.04) as well as between acute and chronic inflammation (p=0.005) were statistically significant. No differences were detected after stimulation between chronic inflammation (1.2 x 10{sup -3} mm{sup 2}/s) and healthy volunteers (p=0.94) and between acute and chronic inflammation (p=0.15), respectively. DW-EPI seems to display the physiological changes of the parotid gland in patients suffering from acute or chronic inflammation and might be useful for discriminating healthy from affected glands. (orig.)

  2. Food-derived bioactive peptides on inflammation and oxidative stress.

    Science.gov (United States)

    Chakrabarti, Subhadeep; Jahandideh, Forough; Wu, Jianping

    2014-01-01

    Chronic diseases such as atherosclerosis and cancer are now the leading causes of morbidity and mortality worldwide. Inflammatory processes and oxidative stress underlie the pathogenesis of these pathological conditions. Bioactive peptides derived from food proteins have been evaluated for various beneficial effects, including anti-inflammatory and antioxidant properties. In this review, we summarize the roles of various food-derived bioactive peptides in inflammation and oxidative stress and discuss the potential benefits and limitations of using these compounds against the burden of chronic diseases.

  3. Linking the microbiota, chronic disease and the immune system

    Science.gov (United States)

    Hand, Timothy W.; Vujkovic-Cvijin, Ivan; Ridaura, Vanessa K.; Belkaid, Yasmine

    2016-01-01

    Chronic inflammatory diseases are the most important causes of mortality in the world today and are on the rise. We now know that immune-driven inflammation is critical in the etiology of these diseases, though the environmental triggers and cellular mechanisms that lead to their development are still mysterious. Many chronic inflammatory diseases are associated with significant shifts in the microbiota towards inflammatory configurations, which can affect the host both by inducing local and systemic inflammation and by alterations in microbiota-derived metabolites. This review discusses recent findings suggesting that shifts in the microbiota may contribute to chronic disease via effects on the immune system. PMID:27623245

  4. Antibody-mediated delivery of interleukin 4 to the neo-vasculature reduces chronic skin inflammation.

    Science.gov (United States)

    Hemmerle, Teresa; Zgraggen, Silvana; Matasci, Mattia; Halin, Cornelia; Detmar, Michael; Neri, Dario

    2014-11-01

    The antibody-mediated delivery of cytokines ("immunocytokines") to sites of pathological angiogenesis represents an attractive strategy for the development of innovative biopharmaceuticals, capable of modulating the activity of the immune system in cancer and in chronic inflammatory conditions. Recombinant IL4 has previously been shown to be therapeutically active in patients with psoriasis. The antibody-mediated delivery of this cytokine to sites of chronic skin inflammatory conditions should lead to an improved potency and selectivity, compared to non-targeted IL4. The therapeutic activity of F8-IL4, a fusion protein of the F8 antibody (specific to the alternatively-spliced EDA domain of fibronectin) with murine IL4, was investigated in three immunocompetent mouse models of skin inflammation: two induced by the TLR7/8 ligand imiquimod (in Balb/c and C57BL/6) and one mediated by the over-expression of VEGF-A. The EDA domain of fibronectin, a marker for angiogenesis, is expressed in the inflamed skin in all three models and F8-IL4 selectively localized to inflamed skin lesions following intravenous administration. The F8-IL4 fusion protein mediated a therapeutic benefit, which was superior to the one of a non-targeted version of IL4 and led to increased levels of key regulatory cytokines (including IL5, IL10, IL13, and IL27) in the inflamed skin, while IL2 levels were not affected in all treatment groups. A murine version of etanercept and a murine anti-IL17 antibody were used as positive control in the therapy experiments. Skin inflammatory lesions can be selectively targeted using anti-EDA antibody-cytokine fusion proteins and the pharmacodelivery of IL4 confers a therapeutic benefit by shifting the cytokine balance. Copyright © 2014 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  5. 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...

  6. The immune response to Prevotella bacteria in chronic inflammatory disease

    DEFF Research Database (Denmark)

    Larsen, Jeppe Madura

    2017-01-01

    the hunt for disease-modulating bacteria. Emerging studies in humans have linked the increased abundance of Prevotella species at mucosal sites to localized and systemic disease, including periodontitis, bacterial vaginosis, rheumatoid arthritis, metabolic disorders and low-grade systemic inflammation....... Intriguingly, Prevotella abundance is reduced within the lung microbiota of patients with asthma and chronic obstructive pulmonary disease. Increased Prevotella abundance is associated with augmented T helper type 17 (Th17) -mediated mucosal inflammation, which is in line with the marked capacity of Prevotella...... and various stromal cells. These findings indicate that some Prevotella strains may be clinically important pathobionts that can participate in human disease by promoting chronic inflammation....

  7. An antiinflammatory dietary mix modulates inflammation and oxidative and metabolic stress in overweight men: A nutrigenomics approach

    NARCIS (Netherlands)

    Bakker, G.C.M.; Erk, M.J. van; Pellis, L.; Wopereis, S.; Rubingh, C.M.; Cnubben, N.H.P.; Kooistra, T.; Ommen, B. van; Hendriks, H.F.J.

    2010-01-01

    Background: Low-grade chronic inflammation in overweight subjects is thought to play an important role in disease development. Objective: It was hypothesized that specific dietary components are able to reduce low-grade inflammation as well as metabolic and oxidative stress. Design: Dietary products

  8. Pulmonary Extramedullary Hematopoiesis in a Patient with Chronic Asthma Resembling Lung Cancer: A Case Report

    Directory of Open Access Journals (Sweden)

    Massood Hosseinzadeh

    2012-01-01

    Full Text Available Background. Extramedullary hematopoiesis is most often seen in reticuloendothelial organs specially spleen, liver, or lymph nodes, and it is rarely seen in lung parenchyma. Almost all reported cases of pulmonary extramedullary hematopoiesis occurred following myeloproliferative disorders specially myelofibrosis. Other less common underlying causes are thalassemia syndromes and other hemoglobinopathies. There was not any reported case of pulmonary extramedullary hematopoiesis in asthmatic patients in the medical literature. Case. Here we reported a 65-year-old lady who was a known case of bronchial asthma with recent developed right lower lobe lung mass. Chest X-ray and CT studies showed an infiltrating mass resembling malignancy. Fine needle aspiration cytology of mass revealed pulmonary extramedullary hematopoiesis. The patient followed for 10 months with serial physical examination and laboratory evaluations which were unremarkable. Conclusion. Extramedullary hematopoiesis of lung parenchyma can be mistaken for lung cancer radiologically. Although previous reported cases occurred with myelofibrosis or hemoglobinopathies, we are reporting the first case of asthma-associated extramedullary hematopoiesis.

  9. Purinergic Receptors in Ocular Inflammation

    Directory of Open Access Journals (Sweden)

    Ana Guzman-Aranguez

    2014-01-01

    Full Text Available Inflammation is a complex process that implies the interaction between cells and molecular mediators, which, when not properly “tuned,” can lead to disease. When inflammation affects the eye, it can produce severe disorders affecting the superficial and internal parts of the visual organ. The nucleoside adenosine and nucleotides including adenine mononucleotides like ADP and ATP and dinucleotides such as P1,P4-diadenosine tetraphosphate (Ap4A, and P1,P5-diadenosine pentaphosphate (Ap5A are present in different ocular locations and therefore they may contribute/modulate inflammatory processes. Adenosine receptors, in particular A2A adenosine receptors, present anti-inflammatory action in acute and chronic retinal inflammation. Regarding the A3 receptor, selective agonists like N6-(3-iodobenzyl-5′-N-methylcarboxamidoadenosine (CF101 have been used for the treatment of inflammatory ophthalmic diseases such as dry eye and uveoretinitis. Sideways, diverse stimuli (sensory stimulation, large intraocular pressure increases can produce a release of ATP from ocular sensory innervation or after injury to ocular tissues. Then, ATP will activate purinergic P2 receptors present in sensory nerve endings, the iris, the ciliary body, or other tissues surrounding the anterior chamber of the eye to produce uveitis/endophthalmitis. In summary, adenosine and nucleotides can activate receptors in ocular structures susceptible to suffer from inflammatory processes. This involvement suggests the possible use of purinergic agonists and antagonists as therapeutic targets for ocular inflammation.

  10. Chemokines in cancer related inflammation

    Energy Technology Data Exchange (ETDEWEB)

    Allavena, Paola; Germano, Giovanni; Marchesi, Federica [Department of Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089, Rozzano, Milan (Italy); Mantovani, Alberto, E-mail: alberto.mantovani@humanitasresearch.it [Department of Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089, Rozzano, Milan (Italy); Department of Translational Medicine, University of Milan (Italy)

    2011-03-10

    Chemokines are key players of the cancer-related inflammation. Chemokine ligands and receptors are downstream of genetic events that cause neoplastic transformation and are abundantly expressed in chronic inflammatory conditions which predispose to cancer. Components of the chemokine system affect multiple pathways of tumor progression including: leukocyte recruitment, neo-angiogenesis, tumor cell proliferation and survival, invasion and metastasis. Evidence in pre-clinical and clinical settings suggests that the chemokine system represents a valuable target for the development of innovative therapeutic strategies.

  11. Middle Ear Infection (Chronic Otitis Media) and Hearing Loss

    Science.gov (United States)

    ... ENT Doctor Near You Middle Ear Infection (Chronic Otitis Media) and Hearing Loss Middle Ear Infection (Chronic ... relations staff at newsroom@entnet.org . What is otitis media? Otitis media refers to inflammation of the ...

  12. 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.

  13. Eosinophilic Chronic Rhinosinusitis in Japan

    Directory of Open Access Journals (Sweden)

    Junichi Ishitoya

    Full Text Available ABSTRACT: Chronic rhinosinusitis is a heterogeneous disease. In Europe and the United States, it has recently been divided into two subgroups: chronic rhinosinusitis with nasal polyps (CRSwNP and chronic rhinosinusitis without nasal polyps (CRSsNP. The majority of CRSwNP cases have a strong tendency to recur after surgery and show eosinophil-dominant inflammation. However, this definition has proved difficult to apply in Japan and East Asia, because more than half of the CRSwNP cases do not exhibit eosinophil-dominant inflammation in these areas of the world. In Japan in the 1990s, refractory CRSwNP to the standard treatment was focused on in clinical studies and the term ''eosinophilic chronic rhinosinusitis'' (ECRS was introduced to identify this subgroup of chronic rhinosinusitis in 2001.ECRS is different from non-ECRS in terms of many clinical features: symptom appearance, occurrence site of nasal polyps, CT scan findings, the histology of nasal polyps, blood examination findings, clinical course after surgery, and co-morbid asthma, etc. In this review, we describe these clinical features and mention how to make a clinical diagnosis of ECRS as well as how to treat it. Finally, we discuss the pathophysiology of ECRS. The concept of ECRS in Japan would be applicable for CRSwNP in other countries including Europe and the United States. KEY WORDS: chronic rhinosinusitis, clinical feature, diagnosis, eosinophilic chronic rhinosinusitis, eosinophils

  14. Role of pattern recognition receptors of the neurovascular unit in inflamm-aging.

    Science.gov (United States)

    Wilhelm, Imola; Nyúl-Tóth, Ádám; Kozma, Mihály; Farkas, Attila E; Krizbai, István A

    2017-11-01

    Aging is associated with chronic inflammation partly mediated by increased levels of damage-associated molecular patterns, which activate pattern recognition receptors (PRRs) of the innate immune system. Furthermore, many aging-related disorders are associated with inflammation. PRRs, such as Toll-like receptors (TLRs) and nucleotide-binding oligomerization domain-like receptors (NLRs), are expressed not only in cells of the innate immune system but also in other cells, including cells of the neurovascular unit and cerebral vasculature forming the blood-brain barrier. In this review, we summarize our present knowledge about the relationship between activation of PRRs expressed by cells of the neurovascular unit-blood-brain barrier, chronic inflammation, and aging-related pathologies of the brain. The most important damage-associated molecular pattern-sensing PRRs in the brain are TLR2, TLR4, and NLR family pyrin domain-containing protein-1 and pyrin domain-containing protein-3, which are activated during physiological and pathological aging in microglia, neurons, astrocytes, and possibly endothelial cells and pericytes. Copyright © 2017 the American Physiological Society.

  15. Inflammation to cancer: The molecular biology in the pancreas (Review).

    Science.gov (United States)

    Ling, Sunbin; Feng, Tingting; Jia, Kaiqi; Tian, Yu; Li, Yan

    2014-06-01

    Inflammatory responses are known to be correlated with cancer initiation and progression, and exploration of the route from inflammation to cancer makes a great contribution in elucidating the mechanisms underlying cancer development. Pancreatic cancer (PC) is a lethal disease with a low radical-resection rate and a poor prognosis. As chronic pancreatitis is considered to be a significant etiological factor for PC development, the current review aims to describe the molecular pathways from inflammation to pancreatic carcinogenesis, in support of the strategies for the prevention, diagnosis and treatment of PC.

  16. Chronic multifocal non-bacterial osteomyelitis in hypophosphatasia mimicking malignancy

    Directory of Open Access Journals (Sweden)

    Warmuth-Metz Monika

    2007-01-01

    Full Text Available Abstract Background Hypophosphatasia (HP is characterized by a genetic defect in the tissue-nonspecific alkaline phosphatase (TNSALP gene and predominantly an autosomal recessive trait. HP patients suffer from reduced bone mineralization. Biochemically, elevated concentrations of substrates of TNSALP, including pyridoxal-5'-phosphate and inorganic pyrophosphate occur in serum, tissues and urine. The latter has been associated with chronic inflammation and hyperprostaglandinism. Case presentation We report on 2 affected children presenting with multifocal inflammatory bone lesions mimicking malignancy: A 6 years old girl with short stature had been treated with human growth hormone since 6 months. Then she started to complain about a painful swelling of her left cheek. MRI suggested a malignant bone lesion. Bone biopsy, however, revealed chronic inflammation. A bone scan showed a second rib lesion. Since biopsy was sterile, the descriptive diagnosis of chronic non-bacterial osteomyelitis (CNO was established. The diagnostic tests related to growth failure were repeated and subsequent analyses demonstrated a molecular defect in the TNSALP gene. The second girl (10 years old complained about back pain after she had fallen from her bike. X rays of her spine revealed compressions of 2 thoracic vertebrae. At first these were considered trauma related, however a bone scan did show an additional lesion in the right 4th rib. A biopsy of this rib revealed a sterile lympho- plasmocytoid osteomyelitis suggesting multifocal CNO. Further analyses did show a decreased TNSALP in leukocytes and elevated pyridoxal phosphate in plasma, suggesting a heterozygous carrier status of HP. Conclusion Chronic bone oedema in adult HP and chronic hyper-prostaglandinism in childhood HP do suggest that in some HP patients bone inflammation is present in conjunction with the metabolic defect. Sterile multifocal osteomyelitis could be demonstrated. Non-steroidal anti

  17. Gut Microbiota Mediates the Protective Effects of Dietary Capsaicin against Chronic Low-Grade Inflammation and Associated Obesity Induced by High-Fat Diet

    Directory of Open Access Journals (Sweden)

    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.

  18. Functional characterization of a competitive peptide antagonist of p65 in human macrophage-like cells suggests therapeutic potential for chronic inflammation

    Directory of Open Access Journals (Sweden)

    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

  19. The Correlation between Chronic Periodontitis and Oral Cancer.

    Science.gov (United States)

    Krüger, Maximilian; Hansen, Torsten; Kasaj, Adrian; Moergel, Maximilian

    2013-01-01

    Infections are increasingly considered as potential trigger for carcinogenesis apart from risk factors like alcohol and tobacco. The discussion about human papilloma virus (HPV) in oral squamous cell carcinoma (OSCC) points at a general role of infection for the development of oral carcinomas. Furthermore, first studies describe a correlation between chronic periodontitis and OSCC, thus, characterizing chronic inflammation as being a possible trigger for OSCC. In front of this background, we present four well-documented clinical cases. All patients showed a significant anatomical relation between OSCC and clinical signs of chronic periodontitis. The interindividual differences of the clinical findings lead to different theoretical concepts: two with coincidental appearance of OSCC and chronic periodontitis and two with possible de novo development of OSCC triggered by chronic inflammation. We conclude that the activation of different inflammatory cascades by chronic periodontitis negatively affects mucosa and bone. Furthermore, the inflammatory response has the potential to activate carcinogenesis. Apart from a mere coincidental occurrence, two out of four patients give first clinical hints for a model wherein chronic periodontitis represents a potential risk factor for the development of OSCC.

  20. The Correlation between Chronic Periodontitis and Oral Cancer

    Directory of Open Access Journals (Sweden)

    Maximilian Krüger

    2013-01-01

    Full Text Available Infections are increasingly considered as potential trigger for carcinogenesis apart from risk factors like alcohol and tobacco. The discussion about human papilloma virus (HPV in oral squamous cell carcinoma (OSCC points at a general role of infection for the development of oral carcinomas. Furthermore, first studies describe a correlation between chronic periodontitis and OSCC, thus, characterizing chronic inflammation as being a possible trigger for OSCC. In front of this background, we present four well-documented clinical cases. All patients showed a significant anatomical relation between OSCC and clinical signs of chronic periodontitis. The interindividual differences of the clinical findings lead to different theoretical concepts: two with coincidental appearance of OSCC and chronic periodontitis and two with possible de novo development of OSCC triggered by chronic inflammation. We conclude that the activation of different inflammatory cascades by chronic periodontitis negatively affects mucosa and bone. Furthermore, the inflammatory response has the potential to activate carcinogenesis. Apart from a mere coincidental occurrence, two out of four patients give first clinical hints for a model wherein chronic periodontitis represents a potential risk factor for the development of OSCC.

  1. Urea synthesis in patients with chronic pancreatitis

    DEFF Research Database (Denmark)

    Hamberg, Ole; Andersen, Vibeke; Sonne, J

    2001-01-01

    Up-regulation of urea synthesis by amino acids and dietary protein intake may be impaired in patients with chronic pancreatitis (CP) due to the reduced glucagon secretion. Conversely, urea synthesis may be increased as a result of the chronic inflammation. The aims of the study were to determine...

  2. 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

  3. Activation and regulation of the pattern recognition receptors in obesity-induced adipose tissue inflammation and insulin resistance.

    Science.gov (United States)

    Watanabe, Yasuharu; Nagai, Yoshinori; Takatsu, Kiyoshi

    2013-09-23

    Obesity-associated chronic tissue inflammation is a key contributing factor to type 2 diabetes mellitus, and a number of studies have clearly demonstrated that the immune system and metabolism are highly integrated. Recent advances in deciphering the various immune cells and signaling networks that link the immune and metabolic systems have contributed to our understanding of the pathogenesis of obesity-associated inflammation. Other recent studies have suggested that pattern recognition receptors in the innate immune system recognize various kinds of endogenous and exogenous ligands, and have a crucial role in initiating or promoting obesity-associated chronic inflammation. Importantly, these mediators act on insulin target cells or on insulin-producing cells impairing insulin sensitivity and its secretion. Here, we discuss how various pattern recognition receptors in the immune system underlie the etiology of obesity-associated inflammation and insulin resistance, with a particular focus on the TLR (Toll-like receptor) family protein Radioprotective 105 (RP105)/myeloid differentiation protein-1 (MD-1).

  4. Activation and Regulation of the Pattern Recognition Receptors in Obesity-Induced Adipose Tissue Inflammation and Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Kiyoshi Takatsu

    2013-09-01

    Full Text Available Obesity-associated chronic tissue inflammation is a key contributing factor to type 2 diabetes mellitus, and a number of studies have clearly demonstrated that the immune system and metabolism are highly integrated. Recent advances in deciphering the various immune cells and signaling networks that link the immune and metabolic systems have contributed to our understanding of the pathogenesis of obesity-associated inflammation. Other recent studies have suggested that pattern recognition receptors in the innate immune system recognize various kinds of endogenous and exogenous ligands, and have a crucial role in initiating or promoting obesity-associated chronic inflammation. Importantly, these mediators act on insulin target cells or on insulin-producing cells impairing insulin sensitivity and its secretion. Here, we discuss how various pattern recognition receptors in the immune system underlie the etiology of obesity-associated inflammation and insulin resistance, with a particular focus on the TLR (Toll-like receptor family protein Radioprotective 105 (RP105/myeloid differentiation protein-1 (MD-1.

  5. The AT2 Receptor and Inflammation

    DEFF Research Database (Denmark)

    Esquitino, Veronica Valero; Danyel, Leon Alexander; Steckelings, Ulrike M.

    2015-01-01

    This chapter summarizes current knowledge about the role of the angiotensin type 2 (AT2) receptor in inflammation. The first section provides an overview about molecular mechanisms underlying the anti-inflammatory action of the AT2 receptor. This section is followed...... by a review of the existing literature addressing the role of the AT2 receptor in a wide range of disorders, in which acute or chronic inflammation is an essential contributor to the pathology. These disorders comprise cardiovascular, cerebrovascular, renal, and autoimmune diseases.Taken as a whole......, the vast majority of data support an anti-inflammatory and immunomodulatory role of the AT2 receptor. In light of the current development of AT2 receptor agonists as future drugs for clinical use, diseases with a marked inflammatory component may become a major area of therapeutic use...

  6. Inflammation as target in cancer therapy.

    Science.gov (United States)

    Marelli, Giulia; Sica, Antonio; Vannucci, Luca; Allavena, Paola

    2017-08-01

    Cells of the innate immunity infiltrating tumour tissues promote, rather than halt, cancer cell proliferation and distant spreading. Tumour-Associated Macrophages (TAMs) are abundantly present in the tumour milieu and here trigger and perpetrate a state of chronic inflammation which ultimately supports disease development and contributes to an immune-suppressive environment. Therapeutic strategies to limit inflammatory cells and their products have been successful in pre-clinical tumour models. Early clinical trials with specific cytokine and chemokine inhibitors, or with strategies designed to target TAMs, are on their way in different solid malignancies. Partial clinical responses and stabilization of diseases were observed in some patients, in the absence of significant toxicity. These encouraging results open new perspectives of combination treatments aimed at reducing cancer-promoting inflammation to maximize the anti-tumour efficacy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Different types of intranasal steroids for chronic rhinosinusitis

    NARCIS (Netherlands)

    Chong, Lee Yee; Head, Karen; Hopkins, Claire; Philpott, Carl; Burton, Martin J; Schilder, Anne G M

    2016-01-01

    BACKGROUND: This review is one of six looking at the primary medical management options for patients with chronic rhinosinusitis.Chronic rhinosinusitis is common and is characterised by inflammation of the lining of the nose and paranasal sinuses leading to nasal blockage, nasal discharge, facial

  8. Persistent systemic inflammation is associated with poor clinical outcomes in COPD

    DEFF Research Database (Denmark)

    Agustí, Alvar; Edwards, Lisa D; Rennard, Stephen I

    2012-01-01

    Because chronic obstructive pulmonary disease (COPD) is a heterogeneous condition, the identification of specific clinical phenotypes is key to developing more effective therapies. To explore if the persistence of systemic inflammation is associated with poor clinical outcomes in COPD we assessed...

  9. A dual role for the immune response in a mouse model of inflammation-associated lung cancer

    OpenAIRE

    Dougan, Michael; Li, Danan; Neuberg, Donna; Mihm, Martin; Googe, Paul; Wong, Kwok-Kin; Dranoff, Glenn

    2011-01-01

    Lung cancer is the leading cause of cancer death worldwide. Both principal factors known to cause lung cancer, cigarette smoke and asbestos, induce pulmonary inflammation, and pulmonary inflammation has recently been implicated in several murine models of lung cancer. To further investigate the role of inflammation in the development of lung cancer, we generated mice with combined loss of IFN-γ and the β-common cytokines GM-CSF and IL-3. These immunodeficient mice develop chronic pulmonary in...

  10. Immunopathophysiology of inflammatory bowel disease: how genetics link barrier dysfunction and innate immunity to inflammation.

    Science.gov (United States)

    Mehta, Minesh; Ahmed, Shifat; Dryden, Gerald

    2017-08-01

    Inflammatory bowel diseases (IBD) comprise a distinct set of clinical symptoms resulting from chronic or relapsing immune activation and corresponding inflammation within the gastrointestinal (GI) tract. Diverse genetic mutations, encoding important aspects of innate immunity and mucosal homeostasis, combine with environmental triggers to create inappropriate, sustained inflammatory responses. Recently, significant advances have been made in understanding the interplay of the intestinal epithelium, mucosal immune system, and commensal bacteria as a foundation of the pathogenesis of inflammatory bowel disease. Complex interactions between specialized intestinal epithelial cells and mucosal immune cells determine different outcomes based on the environmental input: the development of tolerance in the presence of commensal bacterial or the promotion of inflammation upon recognition of pathogenic organisms. This article reviews key genetic abnormalities involved in inflammatory and homeostatic pathways that enhance susceptibility to immune dysregulation and combine with environmental triggers to trigger the development of chronic intestinal inflammation and IBD.

  11. Middle Ear Infection (Chronic Otitis Media) and Hearing Loss

    Science.gov (United States)

    ... Marketplace Find an ENT Doctor Near You Middle Ear Infection (Chronic Otitis Media) and Hearing Loss Middle Ear Infection (Chronic Otitis ... relations staff at newsroom@entnet.org . What is otitis media? Otitis media refers to inflammation of the middle ...

  12. Cytoplasmic chromatin triggers inflammation in senescence and cancer.

    Science.gov (United States)

    Dou, Zhixun; Ghosh, Kanad; Vizioli, Maria Grazia; Zhu, Jiajun; Sen, Payel; Wangensteen, Kirk J; Simithy, Johayra; Lan, Yemin; Lin, Yanping; Zhou, Zhuo; Capell, Brian C; Xu, Caiyue; Xu, Mingang; Kieckhaefer, Julia E; Jiang, Tianying; Shoshkes-Carmel, Michal; Tanim, K M Ahasan Al; Barber, Glen N; Seykora, John T; Millar, Sarah E; Kaestner, Klaus H; Garcia, Benjamin A; Adams, Peter D; Berger, Shelley L

    2017-10-19

    Chromatin is traditionally viewed as a nuclear entity that regulates gene expression and silencing. However, we recently discovered the presence of cytoplasmic chromatin fragments that pinch off from intact nuclei of primary cells during senescence, a form of terminal cell-cycle arrest associated with pro-inflammatory responses. The functional significance of chromatin in the cytoplasm is unclear. Here we show that cytoplasmic chromatin activates the innate immunity cytosolic DNA-sensing cGAS-STING (cyclic GMP-AMP synthase linked to stimulator of interferon genes) pathway, leading both to short-term inflammation to restrain activated oncogenes and to chronic inflammation that associates with tissue destruction and cancer. The cytoplasmic chromatin-cGAS-STING pathway promotes the senescence-associated secretory phenotype in primary human cells and in mice. Mice deficient in STING show impaired immuno-surveillance of oncogenic RAS and reduced tissue inflammation upon ionizing radiation. Furthermore, this pathway is activated in cancer cells, and correlates with pro-inflammatory gene expression in human cancers. Overall, our findings indicate that genomic DNA serves as a reservoir to initiate a pro-inflammatory pathway in the cytoplasm in senescence and cancer. Targeting the cytoplasmic chromatin-mediated pathway may hold promise in treating inflammation-related disorders.

  13. A vicious circle in chronic lymphoedema pathophysiology?

    DEFF Research Database (Denmark)

    Cucchi, F; Rossmeislova, L; Simonsen, L

    2017-01-01

    Chronic lymphoedema is a disease caused by a congenital or acquired damage to the lymphatic system and characterized by complex chains of pathophysiologic events such as lymphatic fluid stasis, chronic inflammation, lymphatic vessels impairment, adipose tissue deposition and fibrosis. These event....... Together, these observations indicate strong reciprocal relationship between lymphatics and adipose tissue and suggest a possible key role of the adipocyte in the pathophysiology of chronic lymphoedema's vicious circle....

  14.  Adiponectin in early and chronic rheumatoid arthritis and osteoarthritis

    DEFF Research Database (Denmark)

    Laurberg, Trine Bay

      Dato 31. januar 2006Title Adiponectin in early and chronic rheumatoid arthritis and osteoarthritisAuthors:Trine Bay Laurberg,Torkell Ellingsen,Jan Frystyk,Ib Hansen,Anette Jørgensen,Ulrik Tarp,Merete Lund Hetland,Kim Hørslev-Petersen,Nete Hornung,Jørgen Hjelm Poulsen,Allan Flyvbjerg,Kristian St......  Dato 31. januar 2006Title Adiponectin in early and chronic rheumatoid arthritis and osteoarthritisAuthors:Trine Bay Laurberg,Torkell Ellingsen,Jan Frystyk,Ib Hansen,Anette Jørgensen,Ulrik Tarp,Merete Lund Hetland,Kim Hørslev-Petersen,Nete Hornung,Jørgen Hjelm Poulsen,Allan Flyvbjerg......,Kristian Stengaard-PedersenBackground: Rheumatoid arthritis (RA) is a systemic, chronic, autoimmune disease, which affects the joints with inflammation leading to destruction of cartilage and bone. Osteoarthritis (OA) is a degenerative joint disease characterised by low level of chronic inflammation, slow...

  15. Is male factor infertility associated with midlife low-grade inflammation?

    DEFF Research Database (Denmark)

    Hærvig, Katia Keglberg; Kierkegaard, Lene; Lund, Rikke

    2017-01-01

    Male factor infertility is associated with an increased risk of disease and mortality, which has been related to markers of chronic systemic inflammation. The objective of this study was to investigate the association between male factor infertility and low-grade inflammation and furthermore...... to examine the lifetime prevalence of male factor infertility and overall infertility (also including female and couple infertility). The study population consisted of 2140 members of the Metropolit 1953 Danish Male Birth Cohort who had participated in the Copenhagen Aging and Midlife Biobank data collection...... in 2009-2011. Information on male factor infertility and overall infertility was obtained from a questionnaire, and low-grade inflammation was evaluated as the highest plasma levels of C-reactive protein, interleukin-6 and tumour necrosis factor-alpha in the population. The level of interleukin-6...

  16. Gut Microbiota Mediates the Protective Effects of Dietary Capsaicin against Chronic Low-Grade Inflammation and Associated Obesity Induced by High-Fat Diet.

    Science.gov (United States)

    Kang, Chao; Wang, Bin; Kaliannan, Kanakaraju; Wang, Xiaolan; Lang, Hedong; Hui, Suocheng; Huang, Li; Zhang, Yong; Zhou, Ming; Chen, Mengting; Mi, Mantian

    2017-05-23

    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 (CB 1 ) 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. IMPORTANCE Metabolic endotoxemia due to gut microbial dysbiosis is a major contributor to the pathogenesis of

  17. A new look at auranofin, dextromethorphan and rosiglitazone for reduction of glia-mediated inflammation in neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Jocelyn M Madeira

    2015-01-01

    Full Text Available Neurodegenerative disorders including Alzheimer′s disease are characterized by chronic inflammation in the central nervous system. The two main glial types involved in inflammatory reactions are microglia and astrocytes. While these cells normally protect neurons by providing nutrients and growth factors, disease specific stimuli can induce glial secretion of neurotoxins. It has been hypothesized that reducing glia-mediated inflammation could diminish neuronal loss. This hypothesis is supported by observations that chronic use of non-steroidal anti-inflammatory drugs (NSAIDs is linked with lower incidences of neurodegenerative disease. It is possible that the NSAIDs are not potent enough to appreciably reduce chronic neuroinflammation after disease processes are fully established. Gold thiol compounds, including auranofin, comprise another class of medications effective at reducing peripheral inflammation. We have demonstrated that auranofin inhibits human microglia- and astrocyte-mediated neurotoxicity. Other drugs which are currently used to treat peripheral inflammatory conditions could be helpful in neurodegenerative disease. Three different classes of anti-inflammatory compounds, which have a potential to inhibit neuroinflammation are highlighted below.

  18. A comparative study between infectious and systemic inflammation

    Directory of Open Access Journals (Sweden)

    Anindhya Sundar Das

    2017-10-01

    Full Text Available Activation of innate immune system may occur as a result of either external (mostly infection-mediated inflammation or internal factors (systemic inflammation. Distinct stimuli act on the immune cells to induce diverse pathways leading to characteristic gene expressions in these cases. Bacterial inflammation, caused primarily by its lipopolysaccharides (LPS, conceives an array of diseases including intestinal bowel disease (IBD, ulcerative colitis and sepsis. In contrast, release of pro-inflammatory cytokines such as IL-6 or TNF-α leads to chronic inflammatory diseases, for example, rheumatoid arthritis (RA, juvenile idiopathic arthritis, Castleman’s disease, etc. It is important to understand the signatures of infectious and systemic gene expression for better designing of treatment regime against inflammatory diseases. To understand the distinctive pattern of gene expression between infectious inflammation and systemic inflammation, THP-1 macrophages were treated individually with LPS (100 ng/mL, IL-6 (50 ng/mL or TNF-α (10 ng/mL and global transcriptomic analysis was performed using Agilent’s human 8x15K array. The common set of differentially expressed genes in IL-6 and TNF-α-treated cohorts were compared with LPS-treated cohorts. Our analysis revealed that 2743 and 150 genes contributed to LPS-mediated inflammation and systemic inflammation with respect to untreated samples, respectively (fold change ≥ 1.5. 868 commonly expressed genes contributed to systemic inflammation with respect to LPS-mediated inflammation. Among these commonly expressed genes, only 68 genes were observed to contribute to both types of inflammation, suggesting their importance in activation of diverse pathways in LPS-mediated and systemic inflammation. A detailed functional annotation of these genes revealed that EGR1, JUN, NF-kB, REL, STAT-1 and BCL-3 are important transcription factors (TFs for distinctive signatures between these two types of inflammation

  19. Prevention of human cancer by modulation of chronic inflammatory processes

    Energy Technology Data Exchange (ETDEWEB)

    Ohshima, Hiroshi [International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon Cedex 08 (France)]. E-mail: ohshima@iarc.fr; Tazawa, Hiroshi [International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon Cedex 08 (France); Sylla, Bakary S. [International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon Cedex 08 (France); Sawa, Tomohiro [International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon Cedex 08 (France)

    2005-12-11

    Chronic inflammation induced by biological, chemical and physical factors has been associated with increased risk of human cancer at various sites. Inflammation facilitates the initiation of normal cells and their growth and progression to malignancy through production of pro-inflammatory cytokines and diverse reactive oxygen and nitrogen species. These also activate signaling molecules involved in inflammation and carcinogenesis such as nuclear transcription factor (NF-{kappa}B), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Several chemopreventive agents act through inhibition of signaling pathways (e.g. NF-{kappa}B), inhibition of oxidant-generating enzymes (e.g. iNOS) and mediators of inflammation (e.g. COX-2), scavenging reactive oxygen and nitrogen species, and modulation of xenobiotic-metabolizing enzymes (especially phase II enzyme induction). Some anti-inflammatory drugs have been tested in clinical trials to prevent human cancer at several sites. Better understanding of the molecular mechanisms by which chronic inflammation increases cancer risk will lead to further development of new strategies for cancer prevention at many sites.

  20. [Marjolin ulcer; malignant degeneration in a chronic wound

    NARCIS (Netherlands)

    Jager, W.C.C. de; Walbeehm, E.T.; Wagner, T.; Gerritsen, M.J.P.

    2015-01-01

    BACKGROUND: A chronic ulcerating wound may turn malignant. The term 'Marjolin ulcer' is used to describe any skin malignancy which develops in an area of chronic ulceration, irritation or inflammation. It is generally a squamous cell carcinoma. CASE DESCRIPTION: A 66-year-old woman was admitted

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

    Directory of Open Access Journals (Sweden)

    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.

  2. miR-34a-mediated regulation of XIST in female cells under inflammation

    Directory of Open Access Journals (Sweden)

    Shenoda BB

    2018-05-01

    Full Text Available Botros B Shenoda,1 Yuzhen Tian,1 Guillermo M Alexander,2 Enrique Aradillas-Lopez,2,3 Robert J Schwartzman,2 Seena K Ajit1 1Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, PA, USA; 2Neurology, Drexel University College of Medicine, Philadelphia, PA, USA; 3Vincera Institute, Philadelphia, PA, USA Background: Evidence is overwhelming for sex differences in pain, with women representing the majority of the chronic pain patient population. There is a need to explore novel avenues to elucidate this sex bias in the development of chronic inflammatory pain conditions. Complex regional pain syndrome (CRPS is a chronic neuropathic pain disorder, and the incidence of CRPS is greater in women than in men by ~4:1. Since neurogenic inflammation is a key feature of CRPS, dysregulation of inflammatory responses can be a factor in predisposing women to chronic pain.Methods: Our studies investigating alterations in circulating microRNAs (miRNAs in whole blood from female CRPS patients showed significant differential expression of miRNAs between responders and poor responders to ketamine treatment. Several of these miRNAs are predicted to target the long noncoding RNA, X-inactive-specific transcript (XIST. XIST mediates X-chromosome inactivation and is essential for equalizing the expression of X-linked genes between females and males. Based on the well-established role in inflammatory process, we focused on miR-34a, one of the miRNAs predicted to target XIST, and downregulated in CRPS patients responding poorly to ketamine. Results: Our in vitro and in vivo models of acute inflammation and data from patients with CRPS showed that miR-34a can regulate XIST under inflammation directly, and through proinflammatory transcription factor Yin-Yang 1 (YY1. XIST was significantly upregulated in a subset of CRPS patients responding poorly to ketamine.Conclusion: Since dysregulation of XIST can result in genes escaping inactivation or

  3. Phenotypic complementation of genetic immunodeficiency by chronic herpesvirus infection.

    Science.gov (United States)

    MacDuff, Donna A; Reese, Tiffany A; Kimmey, Jacqueline M; Weiss, Leslie A; Song, Christina; Zhang, Xin; Kambal, Amal; Duan, Erning; Carrero, Javier A; Boisson, Bertrand; Laplantine, Emmanuel; Israel, Alain; Picard, Capucine; Colonna, Marco; Edelson, Brian T; Sibley, L David; Stallings, Christina L; Casanova, Jean-Laurent; Iwai, Kazuhiro; Virgin, Herbert W

    2015-01-20

    Variation in the presentation of hereditary immunodeficiencies may be explained by genetic or environmental factors. Patients with mutations in HOIL1 (RBCK1) present with amylopectinosis-associated myopathy with or without hyper-inflammation and immunodeficiency. We report that barrier-raised HOIL-1-deficient mice exhibit amylopectin-like deposits in the myocardium but show minimal signs of hyper-inflammation. However, they show immunodeficiency upon acute infection with Listeria monocytogenes, Toxoplasma gondii or Citrobacter rodentium. Increased susceptibility to Listeria was due to HOIL-1 function in hematopoietic cells and macrophages in production of protective cytokines. In contrast, HOIL-1-deficient mice showed enhanced control of chronic Mycobacterium tuberculosis or murine γ-herpesvirus 68 (MHV68), and these infections conferred a hyper-inflammatory phenotype. Surprisingly, chronic infection with MHV68 complemented the immunodeficiency of HOIL-1, IL-6, Caspase-1 and Caspase-1;Caspase-11-deficient mice following Listeria infection. Thus chronic herpesvirus infection generates signs of auto-inflammation and complements genetic immunodeficiency in mutant mice, highlighting the importance of accounting for the virome in genotype-phenotype studies.

  4. Lung Surfactant Protein D (SP-D) Response and Regulation During Acute and Chronic Lung Injury

    DEFF Research Database (Denmark)

    Gaunsbaek, Maria Quisgaard; Rasmussen, Karina Juhl; Beers, Michael F.

    2013-01-01

    in three murine models of lung injury, using a validated ELISA technology for estimation of SP-D levels. METHODS: Mice were exposed to lipopolysaccharide, bleomycin, or Pneumocystis carinii (Pc) and sacrificed at different time points. RESULTS: In lipopolysaccharide-challenged mice, the level of SP...... injury, with a sustained increment during chronic inflammation compared with acute inflammation. A quick upregulation of SP-D in serum in response to acute airway inflammation supports the notion that SP-D translocates from the airways into the vascular system, in favor of being synthesized systemically....... The study also confirms the concept of using increased SP-D serum levels as a biomarker of especially chronic airway inflammation....

  5. The role of inflammation in hypoxic pulmonary hypertension: from cellular mechanisms to clinical phenotypes

    Science.gov (United States)

    Poth, Jens M.; Fini, Mehdi A.; Olschewski, Andrea; El Kasmi, Karim C.; Stenmark, Kurt R.

    2014-01-01

    Hypoxic pulmonary hypertension (PH) comprises a heterogeneous group of diseases sharing the common feature of chronic hypoxia-induced pulmonary vascular remodeling. The disease is usually characterized by mild to moderate pulmonary vascular remodeling that is largely thought to be reversible compared with the progressive irreversible disease seen in World Health Organization (WHO) group I disease. However, in these patients, the presence of PH significantly worsens morbidity and mortality. In addition, a small subset of patients with hypoxic PH develop “out-of-proportion” severe pulmonary hypertension characterized by pulmonary vascular remodeling that is irreversible and similar to that in WHO group I disease. In all cases of hypoxia-related vascular remodeling and PH, inflammation, particularly persistent inflammation, is thought to play a role. This review focuses on the effects of hypoxia on pulmonary vascular cells and the signaling pathways involved in the initiation and perpetuation of vascular inflammation, especially as they relate to vascular remodeling and transition to chronic irreversible PH. We hypothesize that the combination of hypoxia and local tissue factors/cytokines (“second hit”) antagonizes tissue homeostatic cellular interactions between mesenchymal cells (fibroblasts and/or smooth muscle cells) and macrophages and arrests these cells in an epigenetically locked and permanently activated proremodeling and proinflammatory phenotype. This aberrant cellular cross-talk between mesenchymal cells and macrophages promotes transition to chronic nonresolving inflammation and vascular remodeling, perpetuating PH. A better understanding of these signaling pathways may lead to the development of specific therapeutic targets, as none are currently available for WHO group III disease. PMID:25416383

  6. The silencing of cathepsin K used in gene therapy for periodontal disease reveals the role of cathepsin K in chronic infection and inflammation.

    Science.gov (United States)

    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. Angiotensin-(1-7 relieved renal injury induced by chronic intermittent hypoxia in rats by reducing inflammation, oxidative stress and fibrosis

    Directory of Open Access Journals (Sweden)

    W. Lu

    Full Text Available We aimed to study the renal injury and hypertension induced by chronic intermittent hypoxia (CIH and the protective effects mediated by angiotensin 1-7 [Ang(1-7]. We randomly assigned 32 male Sprague-Dawley rats (body weight 180-200 g to normoxia control, CIH, Ang(1-7-treated normoxia, and Ang(1-7-treated CIH groups. Systolic blood pressure (SBP was monitored at the start and end of each week. Renal sympathetic nerve activity (RSNA was recorded. CTGF and TGF-β were detected by immunohistochemistry and western blotting. Tissue parameters of oxidative stress were also determined. In addition, renal levels of interleukin-6, tumor necrosis factor-α, nitrotyrosine, and hypoxia-inducible factor-1α were determined by immunohistochemistry, immunoblotting, and ELISA. TUNEL assay results and cleaved caspase 3 and 12 were also determined. Ang(1-7 induced a reduction in SBP together with a restoration of RSNA in the rat model of CIH. Ang(1-7 treatment also suppressed the production of reactive oxygen species, reduced renal tissue inflammation, ameliorated mesangial expansion, and decreased renal fibrosis. Thus, Ang(1-7 treatment exerted renoprotective effects on CIH-induced renal injury and was associated with a reduction of oxidative stress, inflammation and fibrosis. Ang(1-7 might therefore represent a promising therapy for obstructive sleep apnea-related hypertension and renal injury.

  8. New Insights into the Roles for Basophils in Acute and Chronic Allergy

    Directory of Open Access Journals (Sweden)

    Kaori Mukai

    2009-01-01

    Full Text Available Basophils represent less than 1% of peripheral blood leukocytes. They are often recruited to the site of allergic inflammation, albeit in small numbers. However, it remained uncertain whether basophils play any significant role in allergic reactions or act as minor and redundant 'circulating mast cells'. We have recently demonstrated that basophils play critical roles in systemic anaphylaxis and chronic allergic inflammation, distinctively from mast cells. Basophils are one of the major players in the IgG-but not IgE-mediated systemic anaphylaxis, in contrast to mast cells. In response to the allergen-IgG immune complexes, basophils release the platelet-activating factor rather than histamine as the major chemical mediator to induce the systemic anaphylaxis. The depletion of basophils protects mice from death due to anaphylactic shock. Basophils also play a crucial role in the development of the IgE-mediated chronic allergic inflammation with massive eosinophil infiltration in the skin, independently of T cells and mast cells, even though basophils account for only ~2% of the infiltrates. The basophil depletion shows a therapeutic effect on on-going allergic inflammation. Accumulating evidence suggests that basophils function as initiators rather than effectors of the chronic allergic inflammation. Thus, basophils and their products seem to be promising therapeutic targets for allergic disorders.

  9. High-fat diet-induced adiposity, adipose inflammation, hepatic steatosis and hyperinsulinemia in outbred CD-1 mice.

    Science.gov (United States)

    Gao, Mingming; Ma, Yongjie; Liu, Dexi

    2015-01-01

    High-fat diet (HFD) has been applied to a variety of inbred mouse strains to induce obesity and obesity related metabolic complications. In this study, we determined HFD induced development of metabolic disorders on outbred female CD-1 mice in a time dependent manner. Compared to mice on regular chow, HFD-fed CD-1 mice gradually gained more fat mass and consequently exhibited accelerated body weight gain, which was associated with adipocyte hypertrophy and up-regulated expression of adipose inflammatory chemokines and cytokines such as Mcp-1 and Tnf-α. Increased fat accumulation in white adipose tissue subsequently led to ectopic fat deposition in brown adipose tissue, giving rise to whitening of brown adipose tissue without altering plasma level of triglyceride. Ectopic fat deposition was also observed in the liver, which was associated with elevated expression of key genes involved in hepatic lipid sequestration, including Ppar-γ2, Cd36 and Mgat1. Notably, adipose chronic inflammation and ectopic lipid deposition in the liver and brown fat were accompanied by glucose intolerance and insulin resistance, which was correlated with hyperinsulinemia and pancreatic islet hypertrophy. Collectively, these results demonstrate sequentially the events that HFD induces physiological changes leading to metabolic disorders in an outbred mouse model more closely resembling heterogeneity of the human population.

  10. 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.

  11. Facial Resemblance Exaggerates Sex-Specific Jealousy-Based Decisions1

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    Steven M. Platek

    2007-01-01

    Full Text Available Sex differences in reaction to a romantic partner's infidelity are well documented and are hypothesized to be attributable to sex-specific jealousy mechanisms which are utilized to solve adaptive problems associated with risk of extra-pair copulation. Males, because of the risk of cuckoldry become more upset by sexual infidelity, while females, because of loss of resources and biparental investment tend to become more distressed by emotional infidelity. However, the degree to which these sex-specific reactions to jealousy interact with cues to kin are completely unknown. Here we investigated the interaction of facial resemblance with decisions about sex-specific jealousy scenarios. Fifty nine volunteers were asked to imagine that two different people (represented by facial composites informed them about their romantic partner's sexual or emotional infidelity. Consistent with previous research, males ranked sexual infidelity scenarios as most upsetting and females ranked emotional infidelity scenarios most upsetting. However, when information about the infidelity was provided by a face that resembled the subject, sex-specific reactions to jealousy were exaggerated. This finding highlights the use of facial resemblance as a putative self-referent phenotypic matching cue that impacts trusting behavior in sexual contexts.

  12. [Chronic appendicitis. A case report].

    Science.gov (United States)

    Montiel-Jarquín, Alvaro José; Gómez-Conde, Eduardo; Reyes-Páramo, Pedro; Romero-Briones, Carlos; Mendoza-García, Aurelio Valentín; García-Ramírez, Ulises Noel

    2008-01-01

    The term chronic appendicitis has been used to describe any type of chronic pain that originates in the appendix, with or without inflammation. This broad category can be divided more specifically into: chronic or recurrent appendicitis and appendiceal colic pain. a 41-year-old female, suffering intestinal chronic constipation, abdominal pain, nausea, hiporexia and febricula, treated with antibiotics, vermifuges, analgesics and antispasmodics, showing a slight and partial improvement. She was suffering chronic pain in lower abdomen, mostly on the right side along a year. With these symptoms, she underwent an exploratory laparotomy, that showed chronic appendicitis. Appendix had been removed. The histopathological report corresponded to chronic appendicitis. the histopathological characteristics and the clinical manifestations of the chronic appendicitis are different from those of acute appendicitis. Criteria for chronic appendicitis include: symptoms lasting longer than 4 weeks, confirmation of chronic swelling through histopathological examination, improvement of symptoms after appendectomy. The ultrasonic images, the barium enema and the computerized helicoidal tomography could be suggestive for its diagnosis.

  13. Mycophenolate mofetil combined with systemic corticosteroids prevents progression to chronic recurrent inflammation and development of 'sunset glow fundus' in initial-onset acute uveitis associated with Vogt-Koyanagi-Harada disease.

    Science.gov (United States)

    Abu El-Asrar, Ahmed M; Dosari, Mona; Hemachandran, Suhail; Gikandi, Priscilla W; Al-Muammar, Abdulrahman

    2017-02-01

    To evaluate the effectiveness and safety of mycophenolate mofetil (MMF) as first-line therapy combined with systemic corticosteroids in initial-onset acute uveitis associated with Vogt-Koyanagi-Harada (VKH) disease. This prospective study included 38 patients (76 eyes). The main outcome measures were final visual acuity, corticosteroid-sparing effect, progression to chronic recurrent granulomatous uveitis and development of complications, particularly 'sunset glow fundus'. The mean follow-up period was 37.0 ± 29.3 (range 9-120 months). Visual acuity of 20/20 was achieved by 93.4% of the eyes. Corticosteroid-sparing effect was achieved in all patients. The mean interval between starting treatment and tapering to 10 mg or less daily was 3.8 ± 1.3 months (range 3-7 months). Twenty-two patients (57.9%) discontinued treatment without relapse of inflammation. The mean time observed off of treatment was 28.1 ± 19.6 months (range 1-60 months). None of the eyes progressed to chronic recurrent granulomatous uveitis. The ocular complications encountered were glaucoma in two eyes (2.6%) and cataract in five eyes (6.6%). None of the eyes developed 'sunset glow fundus', and none of the patients developed any systemic adverse events associated with the treatment. Use of MMF as first-line therapy combined with systemic corticosteroids in patients with initial-onset acute VKH disease prevents progression to chronic recurrent granulomatous inflammation and development of 'sunset glow fundus'. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  14. 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...

  15. Emerging Concepts in the Resolution of Periodontal Inflammation: A Role for Resolvin E1

    Directory of Open Access Journals (Sweden)

    Maria G. Balta

    2017-12-01

    Full Text Available Inflammatory response is a protective biological process intended to eliminate the harmful effect of the insulting influx. Resolution of inflammation constitutes an active sequence of overlapping events mediated by specialized proresolving mediators, such as lipoxins, resolvins, protectins, and maresins, which originate from the enzymatic conversion of polyunsaturated fatty acids (PUFAs. An unresolved acute inflammatory response results in chronic inflammation, which is a leading cause of several common pathological conditions. Periodontitis is a biofilm-induced chronic inflammatory disease, which results in loss of periodontal connective tissue and alveolar bone support around the teeth, leading to tooth exfoliation. An inadequate proresolving host response may constitute a mechanism explaining the pathogenesis of periodontal disease. An emerging body of clinical and experimental evidence has focused on the underlying molecular mechanisms of resolvins and particularly Resolvin E1 (RvE1 in periodontitis. Recently, RvE1 has been directly correlated with the resolution of inflammation in periodontal disease. Herein, we provide a comprehensive overview of the literature regarding the role and possible mechanisms of action of RvE1 on different cell populations recruited in periodontal inflammation as well as its potential therapeutic implications. Along with recent data on the benefits of PUFAs supplementation in periodontal clinical parameters, we touch upon suggested future directions for research.

  16. Mathematical modelling as a proof of concept for MPNs as a human inflammation model for cancer development

    DEFF Research Database (Denmark)

    Andersen, Morten; Sajid, Zamra; Pedersen, Rasmus K.

    2017-01-01

    The chronic Philadelphia-negative myeloproliferative neoplasms (MPNs) are acquired stem cell neoplasms which ultimately may transform to acute myelogenous leukemia. Most recently, chronic inflammation has been described as an important factor for the development and progression of MPNs.......The basics of the model describe the proliferation from stem cells to mature cells including mutations of healthy stem cells to become malignant stem cells. We include a simple inflammatory coupling coping with cell death and affecting the basic model beneath. First, we describe the system without feedbacks...... or regulatory interactions. Next, we introduce inflammatory feedback into the system. Finally, we include other feedbacks and regulatory interactions forming the inflammatory-MPN model. Using mathematical modeling, we add further proof to the concept that chronic inflammation may be both a trigger of clonal...

  17. Inhibition of NET Release Fails to Reduce Adipose Tissue Inflammation in Mice

    NARCIS (Netherlands)

    Braster, Quinte; Silvestre Roig, Carlos; Hartwig, Helene; Beckers, Linda; den Toom, Myrthe; Döring, Yvonne; Daemen, Mat J.; Lutgens, Esther; Soehnlein, Oliver

    2016-01-01

    Obesity-associated diseases such as Type 2 diabetes, liver disease and cardiovascular diseases are profoundly mediated by low-grade chronic inflammation of the adipose tissue. Recently, the importance of neutrophils and neutrophil-derived myeloperoxidase and neutrophil elastase on the induction of

  18. Oriental Medical Treatment of chronic Acalculous Cholecystitis

    Directory of Open Access Journals (Sweden)

    Hae-Yeon Lee

    2004-12-01

    Full Text Available Chronic acalculous cholecystitis gets possession of about 12 to 13 percent of patients with chronic cholecystitis. Pathologically it is characterised by chronic inflammation and thickening of the gallbladder wall but doesn't come across stones. Clinical symptoms are vague and include abdominal discomfort and distension, nausea, flatulence and intolerance of fatty foods. A patient on chronic acalculous cholecystitis diagnosed from his clinical symtoms and abdominal ultrasonogram was treated by Geonbihwan, acupuncture and herbal acupuncture. Satisfactory symptomatic improvement was achieved and findings of abdominal ultrasonogram came also normal.

  19. 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.

  20. Estrogen signaling modulates allergic inflammation and contributes to sex differences in asthma.

    Directory of Open Access Journals (Sweden)

    Aleksander eKeselman

    2015-11-01

    Full Text Available Asthma is a chronic airway inflammatory disease that afflicts approximately 300 million people worldwide. It is characterized by airway constriction that leads to wheezing, coughing, and shortness of breath. The most common treatments are corticosteroids and β2-adrenergic receptor antagonists, which target inflammation and airway smooth muscle constriction, respectively. The incidence and severity of asthma is greater in women than in men, and women are more prone to develop corticosteroid-resistant or hard-to-treat asthma. Puberty, menstruation, pregnancy, menopause, and oral contraceptives are known to contribute to disease outcome in women, potentially suggesting a role for estrogen and other hormones impacting allergic inflammation. Currently, the mechanisms underlying these sex differences are poorly understood, although the effect of sex hormones, such as estrogen, on allergic inflammation is gaining interest. Asthma presents as a heterogeneous disease. In typical Th2-type allergic asthma, interleukin-4 and interleukin-13 predominate, driving IgE production and recruitment of eosinophils into the lungs. Chronic Th2-inflammation in the lung results in structural changes and activation of multiple immune cell types, leading to a deterioration of lung function over time. Most immune cells express estrogen receptors (ERα, ERβ, or the membrane-bound G-protein-coupled estrogen receptor to varying degrees and can respond to the hormone. Together these receptors have demonstrated the capacity to regulate a spectrum of immune functions, including adhesion, migration, survival, wound healing, and antibody and cytokine production. This review will cover the current understanding of estrogen signaling in allergic inflammation and discuss how this signaling may contribute to sex differences in asthma and allergy.

  1. Effect of sildenafil on acrolein-induced airway inflammation and mucus production in rats.

    Science.gov (United States)

    Wang, T; Liu, Y; Chen, L; Wang, X; Hu, X-R; Feng, Y-L; Liu, D-S; Xu, D; Duan, Y-P; Lin, J; Ou, X-M; Wen, F-Q

    2009-05-01

    Airway inflammation with mucus overproduction is a distinguishing pathophysiological feature of many chronic respiratory diseases. Phosphodiesterase (PDE) inhibitors have shown anti-inflammatory properties. In the present study, the effect of sildenafil, a potent inhibitor of PDE5 that selectively degrades cyclic guanosine 3',5'-monophosphate (cGMP), on acrolein-induced inflammation and mucus production in rat airways was examined. Rats were exposed to acrolein for 14 and 28 days. Sildenafil or distilled saline was administered intragastrically prior to acrolein exposure. Bronchoalveolar lavage fluid (BALF) was acquired for cell count and the detection of pro-inflammatory cytokine levels. Lung tissue was examined for cGMP content, nitric oxide (NO)-metabolite levels, histopathological lesion scores, goblet cell metaplasia and mucin production. The results suggested that sildenafil pretreatment reversed the significant decline of cGMP content in rat lungs induced by acrolein exposure, and suppressed the increase of lung NO metabolites, the BALF leukocyte influx and pro-inflammatory cytokine release. Moreover, sildenafil pretreatment reduced acrolein-induced Muc5ac mucin synthesis at both mRNA and protein levels, and attenuated airway inflammation, as well as epithelial hyperplasia and metaplasia. In conclusion, sildenafil could attenuate airway inflammation and mucus production in the rat model, possibly through the nitric oxide/cyclic guanosine 3',5'-monophosphate pathway, and, thus, might have a therapeutic potential for chronic airway diseases.

  2. 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.

  3. [Orbital inflammation].

    Science.gov (United States)

    Mouriaux, F; Coffin-Pichonnet, S; Robert, P-Y; Abad, S; Martin-Silva, N

    2014-12-01

    Orbital inflammation is a generic term encompassing inflammatory pathologies affecting all structures within the orbit : anterior (involvement up to the posterior aspect of the globe), diffuse (involvement of intra- and/or extraconal fat), apical (involvement of the posterior orbit), myositis (involvement of only the extraocular muscles), dacryoadenitis (involvement of the lacrimal gland). We distinguish between specific inflammation and non-specific inflammation, commonly referred to as idiopathic inflammation. Specific orbital inflammation corresponds to a secondary localization of a "generalized" disease (systemic or auto-immune). Idiopathic orbital inflammation corresponds to uniquely orbital inflammation without generalized disease, and thus an unknown etiology. At the top of the differential diagnosis for specific or idiopathic orbital inflammation are malignant tumors, represented most commonly in the adult by lympho-proliferative syndromes and metastases. Treatment of specific orbital inflammation begins with treatment of the underlying disease. For idiopathic orbital inflammation, treatment (most often corticosteroids) is indicated above all in cases of visual loss due to optic neuropathy, in the presence of pain or oculomotor palsy. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  4. Microglia are involve in pain related behaviors during the acute and chronic phase of arthritis inflammation

    Directory of Open Access Journals (Sweden)

    Behzad Nasseri

    2016-08-01

    Full Text Available AbstractBackground: Pain is one of the main protests of inflammatory diseases, hence, understanding the mechanisms which involved in the induction and persistence of pain is essential. Microglia is a contributing factor in the onset and maintenance of inflammation. Increased microglial   activation increases the level of central pro-inflammatory cytokines and the development of central sensitization following inflammation. The aim of this study was evaluate the relation of spinal microglia activity with pain related behaviors during Complete Freund’s adjuvant (CFA-induced inflammation.Materials and Methods: Inflammation caused by subcutaneous injection of Complete Freund’s adjuvant (CFA in a single dose to the animals right hind paw. The edema and hyperalgesia caused by inflammation, respectively are measured by Plethysmometer and Radiant Heat, on days 0,7,14 and 21. Spinal Iba-1 protein expression was detected by Western blotting. Minocycline hydrochloride (Sigma, U.S.A was administered i.p. at a dose of 40mg/kg daily.Results: Our study findings indicated that CFA injection to right hindpaw of rats increased paw volume and hyperalgesia significantly during different stages of study, while Minocycline treatment significantly reduced paw volume and hyperalgesia. CFA injection into the right hindpaw of the rat increases the expression of molecules Ionized calcium binding adaptor molecule -1 (Iba-1 on different days of study, while Minocycline administration reduced spinal Iba-1 expression significantly compared to the CFA group.Conclusion: The results of this study indicated the significant roles of microglia activation in deterioration of pain related behaviors during different stages of CFA-induced inflammation. The steady injection of Minocycline (as a microglia inhibitor could reduce the inflammatory symptoms.Keywords: Inflammation, pain, microglia, minocycline

  5. Nitric oxide and chronic colitis

    Directory of Open Access Journals (Sweden)

    Matthew B Grisham

    1996-01-01

    Full Text Available Nitric oxide (NO is thought to play an important role in modulating the inflammatory response by virtue of its ability to affect bloodflow, leukocyte function and cell viability. The objective of this study was to assess the role that NO may play in mediating the mucosal injury and inflammation in a model of chronic granulomatous colitis using two pharmacologically different inhibitors of nitric oxide synthase (NOS. Chronic granulomatous colitis with liver and spleen inflammation was induced in female Lewis rats via the subserosal (intramural injection of peptidoglycan/polysaccharide (PG/PS derived from group A streptococci. Chronic NOS inhibition by oral administration of NG-nitro-L-arginine methyl ester (L-NAME (15 µmol/kg/day or amino-guanidine (AG (15 µmol/ kg/day was found to attenuate the PG/PS-induced increases in macroscopic colonic inflammation scores and colonic myeloperoxidase activity. Only AG -- not L-NAME – attenuated the PG/PS-induced increases in colon dry weight. Both L-NAME and AG significantly attenuated the PG/PS-induced increases in spleen weight whereas neither was effective at significantly attenuating the PG/PS-induced increases in liver weight. Although both L-NAME and AG inhibited NO production in vivo, as measured by decreases in plasma nitrite and nitrate levels, only AG produced significantly lower values (38±3 versus 83±8 µM, respectively, P<0.05. Finally, L-NAME, but not AG, administration significantly increased mean arterial pressure from 83 mmHg in colitic animals to 105 mmHg in the PG/PS+ L-NAME-treated animals (P<0.05. It is concluded that NO may play an important role in mediating some of the pathophysiology associated with this model of chronic granulomatous colitis.

  6. Targeting Neutrophilic Inflammation Using Polymersome-Mediated Cellular Delivery.

    Science.gov (United States)

    Robertson, James D; Ward, Jon R; Avila-Olias, Milagros; Battaglia, Giuseppe; Renshaw, Stephen A

    2017-05-01

    Neutrophils are key effector cells in inflammation and play an important role in neutralizing invading pathogens. During inflammation resolution, neutrophils undergo apoptosis before they are removed by macrophages, but if apoptosis is delayed, neutrophils can cause extensive tissue damage and chronic disease. Promotion of neutrophil apoptosis is a potential therapeutic approach for treating persistent inflammation, yet neutrophils have proven difficult cells to manipulate experimentally. In this study, we deliver therapeutic compounds to neutrophils using biocompatible, nanometer-sized synthetic vesicles, or polymersomes, which are internalized by binding to scavenger receptors and subsequently escape the early endosome through a pH-triggered disassembly mechanism. This allows polymersomes to deliver molecules into the cell cytosol of neutrophils without causing cellular activation. After optimizing polymersome size, we show that polymersomes can deliver the cyclin-dependent kinase inhibitor (R)-roscovitine into human neutrophils to promote apoptosis in vitro. Finally, using a transgenic zebrafish model, we show that encapsulated (R)-roscovitine can speed up inflammation resolution in vivo more efficiently than the free drug. These results show that polymersomes are effective intracellular carriers for drug delivery into neutrophils. This has important consequences for the study of neutrophil biology and the development of neutrophil-targeted therapeutics. Copyright © 2017 The Authors.

  7. Cartilage damage and bone erosion are more prominent determinants of functional impairment in longstanding experimental arthritis than synovial inflammation

    Directory of Open Access Journals (Sweden)

    Silvia Hayer

    2016-11-01

    Full Text Available Chronic inflammation of articular joints causing bone and cartilage destruction consequently leads to functional impairment or loss of mobility in affected joints from individuals affected by rheumatoid arthritis (RA. Even successful treatment with complete resolution of synovial inflammatory processes does not lead to full reversal of joint functionality, pointing to the crucial contribution of irreversibly damaged structural components, such as bone and cartilage, to restricted joint mobility. In this context, we investigated the impact of the distinct components, including synovial inflammation, bone erosion or cartilage damage, as well as the effect of blocking tumor necrosis factor (TNF on functional impairment in human-TNF transgenic (hTNFtg mice, a chronic inflammatory erosive animal model of RA. We determined CatWalk-assisted gait profiles as objective quantitative measurements of functional impairment. We first determined body-weight-independent gait parameters, including maximum intensity, print length, print width and print area in wild-type mice. We observed early changes in those gait parameters in hTNFtg mice at week 5 – the first clinical signs of arthritis. Moreover, we found further gait changes during chronic disease development, indicating progressive functional impairment in hTNFtg mice. By investigating the association of gait parameters with inflammation-mediated joint pathologies at different time points of the disease course, we found a relationship between gait parameters and the extent of cartilage damage and bone erosions, but not with the extent of synovitis in this chronic model. Next, we observed a significant improvement of functional impairment upon blocking TNF, even at progressed stages of disease. However, blocking TNF did not restore full functionality owing to remaining subclinical inflammation and structural microdamage. In conclusion, CatWalk gait analysis provides a useful tool for quantitative

  8. Role of Hydrogen Sulfide in the Pathology of Inflammation

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    Madhav Bhatia

    2012-01-01

    Full Text Available Hydrogen sulfide (H2S is a well-known toxic gas that is synthesized in the human body from the amino acids cystathionine, homocysteine, and cysteine by the action of at least two distinct enzymes: cystathionine-γ-lyase and cystathionine-β-synthase. In the past few years, H2S has emerged as a novel and increasingly important biological mediator. Imbalances in H2S have also been shown to be associated with various disease conditions. However, defining the precise pathophysiology of H2S is proving to be a complex challenge. Recent research in our laboratory has shown H2S as a novel mediator of inflammation and work in several groups worldwide is currently focused on determining the role of H2S in inflammation. H2S has been implicated in different inflammatory conditions, such as acute pancreatitis, sepsis, joint inflammation, and chronic obstructive pulmonary disease (COPD. Active research on the role of H2S in inflammation will unravel the pathophysiology of its actions in inflammatory conditions and may help develop novel therapeutic approaches for several, as yet incurable, disease conditions.

  9. Inflammation Induces TDP-43 Mislocalization and Aggregation.

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    Ana Sofia Correia

    Full Text Available TAR DNA-binding protein 43 (TDP-43 is a major component in aggregates of ubiquitinated proteins in amyotrophic lateral sclerosis (ALS and frontotemporal lobar degeneration (FTLD. Here we report that lipopolysaccharide (LPS-induced inflammation can promote TDP-43 mislocalization and aggregation. In culture, microglia and astrocytes exhibited TDP-43 mislocalization after exposure to LPS. Likewise, treatment of the motoneuron-like NSC-34 cells with TNF-alpha (TNF-α increased the cytoplasmic levels of TDP-43. In addition, the chronic intraperitoneal injection of LPS at a dose of 1mg/kg in TDP-43(A315T transgenic mice exacerbated the pathological TDP-43 accumulation in the cytoplasm of spinal motor neurons and it enhanced the levels of TDP-43 aggregation. These results suggest that inflammation may contribute to development or exacerbation of TDP-43 proteinopathies in neurodegenerative disorders.

  10. Role of Inflammation in Diabetic Retinopathy

    Science.gov (United States)

    Rübsam, Anne; Parikh, Sonia; Fort, Patrice E.

    2018-01-01

    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. PMID:29565290

  11. Role of Inflammation in Diabetic Retinopathy

    Directory of Open Access Journals (Sweden)

    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.

  12. Leukocyte scintiscanning for the diagnosis of inflammations

    International Nuclear Information System (INIS)

    Becker, W.

    1988-01-01

    The value of leukocyte scintiscanning for clinical diagnostics is examined with regard to various areas of indications, and as a method of first examination, or as an alternative to, or additional method to be combined with, the other usual techniques. Leukocyte scintiscanning is indicated as a good first examination method in case of chronic enteritis in a highly active stage, stenosis of the colon, or when abscess is suspected, or infected renal cysts, or infection of angioplasty, osteomyelitis, or in case of fiever of unknown origin and impossible focal diagnosis. It also is applicable for follow-up diagnostics in chronic enteritis, suspected abdominal abscess, prosthetic valvular endocarditis, and infection of hip joint prothesis. The method also may yield additional information in case of renal graft rejection, coronary inflammations, for differential diagnosis of brain tumor or abcess, edematous or antodigestive pancreatitis, and in chronic polyarthritis. For leukocyte labelling, indium-111 and Tc-99m are primarily used. (ECB) [de

  13. Inflammation and race and gender differences in computerized tomography-measured adipose depots

    NARCIS (Netherlands)

    Beasley, L.E.; Koster, A.; Newman, A.B.; Javaid, M.K.; Ferucci, L.; Kritchevsky, S.B.; Kuller, L.H.; Pahor, M.; Visser, M.; Rubin, S.M.; Goodpaster, B.H.; Everhart, J.E.; Harris, T.B.

    2009-01-01

    A growing body of evidence has consistently shown a correlation between obesity and chronic subclinical inflammation. It is unclear whether the size of specific adipose depots is more closely associated with concentrations of inflammatory markers than overall adiposity. This study investigated the

  14. Presence or absence of ocular surface inflammation directs clinical and therapeutic management of dry eye

    OpenAIRE

    Sambursky, Robert

    2016-01-01

    Robert Sambursky Coastal Eye Institute, Cornea and Comprehensive Ophthalmology, Bradenton, FL, USA Background: The presence of clinically significant inflammation has been confirmed in the tears of 40%–65% of patients with symptoms of dry eye. Ocular surface inflammation may lead to tear film instability, epithelial cell irregularities, and permeability, resulting in chronic symptomatic pain and fluctuating vision as well as negative surgical outcomes.Patients and methods: A retro...

  15. Chronic Inflammatory Diseases and Atherosclerotic Cardiovascular Disease

    DEFF Research Database (Denmark)

    Hansen, Peter Riis

    2018-01-01

    Inflammation plays a significant role in atherosclerosis and cardiovascular disease (CVD). Patients with chronic inflammatory diseases are at increased risk of CVD, but it is debated whether this association is causal or dependent on shared risk factors, other exposures, genes, and/or inflammatory...... pathways. The current review summarizes epidemiological, clinical, and experimental data supporting the role of shared inflammatory mechanisms between atherosclerotic CVD and rheumatoid arthritis, psoriasis, inflammatory bowel disease, and periodontitis, respectively, and provides insights to future...... prospects in this area of research. Awareness of the role of inflammation in CVD in patients with chronic inflammatory diseases and the potential for anti-inflammatory therapy, e.g., with tumor necrosis factor-α inhibitors, to also reduce atherosclerotic CVD has evolved into guideline- based recommendations...

  16. Intravitreal Devices for the Treatment of Vitreous Inflammation

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    John B. Christoforidis

    2012-01-01

    Full Text Available The eye is a well-suited organ for local delivery of therapeutics to treat vitreous inflammation as well as other pathologic conditions that induce visual loss. Several conditions are particularly challenging to treat and often require chronic courses of therapy. The use of implantable intravitreal devices for drug delivery is an emerging field in the treatment of vitreous inflammation as well as other ophthalmologic diseases. There are unique challenges in the design of these devices which include implants, polymers, and micro- and nanoparticles. This paper reviews current and investigational drug delivery systems for treating vitreous inflammation as well as other pathologic conditions that induce visual loss. The use of nonbiodegradable devices such as polyvinyl alcohol-ethylene vinyl acetate polymers and polysulfone capillary fibers, and biodegradable devices such as polylactic acid, polyglycolic acid, and polylactic-co-glycolic acid, polycaprolactones, and polyanhydrides are reviewed. Clinically used implantable devices for therapeutic agents including ganciclovir, fluocinolone acetonide, triamcinolone acetonide, and dexamethasone are described. Finally, recently developed investigational particulate drug delivery systems in the form of liposomes, microspheres, and nanoparticles are examined.

  17. Radiation, Inflammation, and Immune Responses in Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Multhoff, Gabriele [Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Munich (Germany); Helmholtz Zentrum München, Clinical Cooperation Group Innate Immunity in Tumor Biology, Munich (Germany); Radons, Jürgen, E-mail: raj10062@web.de [multimmune GmbH, Munich (Germany)

    2012-06-04

    Chronic inflammation has emerged as one of the hallmarks of cancer. Inflammation also plays a pivotal role in modulating radiation responsiveness of tumors. As discussed in this review, ionizing radiation (IR) leads to activation of several transcription factors modulating the expression of numerous mediators in tumor cells and cells of the microenvironment promoting cancer development. Novel therapeutic approaches thus aim to interfere with the activity or expression of these factors, either in single-agent or combinatorial treatment or as supplements of the existing therapeutic concepts. Among them, NF-κB, STAT-3, and HIF-1 play a crucial role in radiation-induced inflammatory responses embedded in a complex inflammatory network. A great variety of classical or novel drugs including nutraceuticals such as plant phytochemicals have the capacity to interfere with the inflammatory network in cancer and are considered as putative radiosensitizers. Thus, targeting the inflammatory signaling pathways induced by IR offers the opportunity to improve the clinical outcome of radiation therapy by enhancing radiosensitivity and decreasing putative metabolic effects. Since inflammation and sex steroids also impact tumorigenesis, a therapeutic approach targeting glucocorticoid receptors and radiation-induced production of tumorigenic factors might be effective in sensitizing certain tumors to IR.

  18. Radiation, Inflammation, and Immune Responses in Cancer

    International Nuclear Information System (INIS)

    Multhoff, Gabriele; Radons, Jürgen

    2012-01-01

    Chronic inflammation has emerged as one of the hallmarks of cancer. Inflammation also plays a pivotal role in modulating radiation responsiveness of tumors. As discussed in this review, ionizing radiation (IR) leads to activation of several transcription factors modulating the expression of numerous mediators in tumor cells and cells of the microenvironment promoting cancer development. Novel therapeutic approaches thus aim to interfere with the activity or expression of these factors, either in single-agent or combinatorial treatment or as supplements of the existing therapeutic concepts. Among them, NF-κB, STAT-3, and HIF-1 play a crucial role in radiation-induced inflammatory responses embedded in a complex inflammatory network. A great variety of classical or novel drugs including nutraceuticals such as plant phytochemicals have the capacity to interfere with the inflammatory network in cancer and are considered as putative radiosensitizers. Thus, targeting the inflammatory signaling pathways induced by IR offers the opportunity to improve the clinical outcome of radiation therapy by enhancing radiosensitivity and decreasing putative metabolic effects. Since inflammation and sex steroids also impact tumorigenesis, a therapeutic approach targeting glucocorticoid receptors and radiation-induced production of tumorigenic factors might be effective in sensitizing certain tumors to IR.

  19. Evidence for local inflammation in complex regional pain syndrome type 1

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    Frank J. P. M. Huygen

    2002-01-01

    Full Text Available Background: The pathophysiology of complex regional pain syndrome type 1 (CRPS 1 is still a matter of debate. Peripheral afferent, efferent and central mechanisms are supposed. Based on clinical signs and symptoms (e.g. oedema, local temperature changes and chronic pain local inflammation is suspected.

  20. A link between inflammation and metastasis

    DEFF Research Database (Denmark)

    Hansen, M. T.; Forst, B.; Cremers, N.

    2015-01-01

    S100A4 is implicated in metastasis and chronic inflammation, but its function remains uncertain. Here we establish an S100A4-dependent link between inflammation and metastatic tumor progression. We found that the acute-phase response proteins serum amyloid A (SAA) 1 and SAA3 are transcriptional...... targets of S100A4 via Toll-like receptor 4 (TLR4)/nuclear factor-κB signaling. SAA proteins stimulated the transcription of RANTES (regulated upon activation normal T-cell expressed and presumably secreted), G-CSF (granulocyte-colony-stimulating factor) and MMP2 (matrix metalloproteinase 2), MMP3, MMP9...... and MMP13. We have also shown for the first time that SAA stimulate their own transcription as well as that of proinflammatory S100A8 and S100A9 proteins. Moreover, they strongly enhanced tumor cell adhesion to fibronectin, and stimulated migration and invasion of human and mouse tumor cells...

  1. Traumatic bone cyst resembling apical periodontitis.

    Science.gov (United States)

    Rosen, D J; Ardekian, L; Machtei, E E; Peled, M; Manor, R; Laufer, D

    1997-10-01

    Among the pseudocysts of the jaws, the traumatic bone cyst is known as an asymptomatic lesion often noted unintentionally during routine radiographic examinations. The lesion neither devitalizes the teeth within its borders, nor does it cause resorption of their roots. The well-demarcated traumatic bone cyst often projects into the intraradicular septa and hence has been described as having scalloped borders. The following presentation is of a traumatic bone cyst that resembled periodontal pathology in its appearance.

  2. Macrophage Polarization in Chronic Inflammatory Diseases: Killers or Builders?

    Science.gov (United States)

    Baci, Denisa; Tremolati, Marco; Fanuli, Matteo; Farronato, Giampietro; Mortara, Lorenzo

    2018-01-01

    Macrophages are key cellular components of the innate immunity, acting as the main player in the first-line defence against the pathogens and modulating homeostatic and inflammatory responses. Plasticity is a major feature of macrophages resulting in extreme heterogeneity both in normal and in pathological conditions. Macrophages are not homogenous, and they are generally categorized into two broad but distinct subsets as either classically activated (M1) or alternatively activated (M2). However, macrophages represent a continuum of highly plastic effector cells, resembling a spectrum of diverse phenotype states. Induction of specific macrophage functions is closely related to the surrounding environment that acts as a relevant orchestrator of macrophage functions. This phenomenon, termed polarization, results from cell/cell, cell/molecule interaction, governing macrophage functionality within the hosting tissues. Here, we summarized relevant cellular and molecular mechanisms driving macrophage polarization in “distant” pathological conditions, such as cancer, type 2 diabetes, atherosclerosis, and periodontitis that share macrophage-driven inflammation as a key feature, playing their dual role as killers (M1-like) and/or builders (M2-like). We also dissect the physio/pathological consequences related to macrophage polarization within selected chronic inflammatory diseases, placing polarized macrophages as a relevant hallmark, putative biomarkers, and possible target for prevention/therapy. PMID:29507865

  3. Macrophage Polarization in Chronic Inflammatory Diseases: Killers or Builders?

    Directory of Open Access Journals (Sweden)

    Luca Parisi

    2018-01-01

    Full Text Available Macrophages are key cellular components of the innate immunity, acting as the main player in the first-line defence against the pathogens and modulating homeostatic and inflammatory responses. Plasticity is a major feature of macrophages resulting in extreme heterogeneity both in normal and in pathological conditions. Macrophages are not homogenous, and they are generally categorized into two broad but distinct subsets as either classically activated (M1 or alternatively activated (M2. However, macrophages represent a continuum of highly plastic effector cells, resembling a spectrum of diverse phenotype states. Induction of specific macrophage functions is closely related to the surrounding environment that acts as a relevant orchestrator of macrophage functions. This phenomenon, termed polarization, results from cell/cell, cell/molecule interaction, governing macrophage functionality within the hosting tissues. Here, we summarized relevant cellular and molecular mechanisms driving macrophage polarization in “distant” pathological conditions, such as cancer, type 2 diabetes, atherosclerosis, and periodontitis that share macrophage-driven inflammation as a key feature, playing their dual role as killers (M1-like and/or builders (M2-like. We also dissect the physio/pathological consequences related to macrophage polarization within selected chronic inflammatory diseases, placing polarized macrophages as a relevant hallmark, putative biomarkers, and possible target for prevention/therapy.

  4. Inflamm-aging and arachadonic acid metabolite differences with stage of tendon disease.

    Directory of Open Access Journals (Sweden)

    Stephanie Georgina Dakin

    Full Text Available The contribution of inflammation to the pathogenesis of tendinopathy and high prevalence of re-injury is not well established, although recent evidence suggests involvement of prostaglandins. We investigated the roles of prostaglandins and inflammation-resolving mediators in naturally occurring equine tendon injury with disease stage and age. Levels of prostaglandins E(2 (PGE(2, F(2α (PGF(2α, lipoxin A(4 (LXA(4 and its receptor FPR2/ALX were analysed in extracts of normal, sub-acute and chronic injured tendons. To assess whether potential changes were associated with altered PGE(2 metabolism, microsomal prostaglandin E synthase-1 (mPGES-1, prostaglandin dehydrogenase (PGDH, COX-2 and EP(4 receptor expression were investigated. The ability of tendons to resolve inflammation was determined by assessing FPR2/ALX expression in natural injury and IL-1β stimulated tendon explants.Alterations in the profile of lipid mediators during sub-acute injury included low PGE(2 and elevated LXA(4 levels compared to normal and chronic injuries. In contrast, PGF(2α levels remained unchanged and were three-fold lower than PGE(2. The synthetic capacity of PGE(2 as measured by the ratio of mPGES-1:PGDH was elevated in sub-acute injury, suggesting aberrations in tendon prostaglandin metabolism, whilst COX-2 and EP(4 receptor were unchanged. Paradoxically low tendon PGE(2 levels in early injury may be attributed to increased local clearance via PGDH or the class switching of lipid mediators from the prostaglandin to the lipoxin axis. PGE(2 is therefore implicated in the development of tendon inflammation and its ensuing resolution. Whilst there was no relationship between age and tendon LXA(4 levels, there was an age-associated decline in FPR2/ALX receptor expression with concurrent increased PGE(2 levels in injury. Furthermore, uninjured tendon explants from younger (<10 years but not older horses (≥10 years treated with IL-1β responded by increasing FPR2/ALX

  5. Macrophage sub-populations and the lipoxin A4 receptor implicate active inflammation during equine tendon repair.

    Directory of Open Access Journals (Sweden)

    Stephanie Georgina Dakin

    Full Text Available Macrophages (Mφ orchestrate inflammatory and reparatory processes in injured connective tissues but their role during different phases of tendon healing is not known. We investigated the contribution of different Mφ subsets in an equine model of naturally occurring tendon injury. Post mortem tissues were harvested from normal (uninjured, sub-acute (3-6 weeks post injury and chronically injured (>3 months post injury superficial digital flexor tendons. To determine if inflammation was present in injured tendons, Mφ sub-populations were quantified based on surface antigen expression of CD172a (pan Mφ, CD14(highCD206(low (pro-inflammatory M1Mφ, and CD206(high (anti-inflammatory M2Mφ to assess potential polarised phenotypes. In addition, the Lipoxin A(4 receptor (FPR2/ALX was used as marker for resolving inflammation. Normal tendons were negative for both Mφ and FPR2/ALX. In contrast, M1Mφ predominated in sub-acute injury, whereas a potential phenotype-switch to M2Mφ polarity was seen in chronic injury. Furthermore, FPR2/ALX expression by tenocytes was significantly upregulated in sub-acute but not chronic injury. Expression of the FPR2/ALX ligand Annexin A1 was also significantly increased in sub-acute and chronic injuries in contrast to low level expression in normal tendons. The combination of reduced FPR2/ALX expression and persistence of the M2Mφ phenotype in chronic injury suggests a potential mechanism for incomplete resolution of inflammation after tendon injury. To investigate the effect of pro-inflammatory mediators on lipoxin A(4 (LXA(4 production and FPR2/ALX expression in vitro, normal tendon explants were stimulated with interleukin-1 beta and prostaglandin E(2. Stimulation with either mediator induced LXA(4 release and maximal upregulation of FPR2/ALX expression after 72 hours. Taken together, our data suggests that although tenocytes are capable of mounting a protective mechanism to counteract inflammatory stimuli, this

  6. Inhibition of NFκB by the natural product Withaferin A in cellular models of Cystic Fibrosis inflammation

    Directory of Open Access Journals (Sweden)

    Huang Shan

    2009-05-01

    Full Text Available Abstract Cystic Fibrosis (CF is one of the most common autosomal genetic disorders in humans. This disease is caused by mutations within a single gene, coding for the cystic fibrosis transmembrane conductance regulator (CFTR protein. The phenotypic hallmark of CF is chronic lung infection and associated inflammation from opportunistic microbes such as Pseudomonas aeruginosa (PA, Haemophilus influenzae, and Staphylococcus aureus. This eventually leads to deterioration of lung function and death in most CF patients. Unfortunately, there is no approved therapy for correcting the genetic defect causal to the disease. Hence, controlling inflammation and infection in CF patients are critical to disease management. Accordingly, anti-inflammatory agents and antibiotics are used to manage chronic inflammation and infection in CF patients. However, most of the anti-inflammatory agents in CF have severe limitations due to adverse side effects, and resistance to antibiotics is becoming an even more prominent problem. Thus, new agents that can be used to control chronic inflammation in CF are needed in the absence of a cure for the disease. Activation of the transcription factor NFκB through Toll-like receptors (TLR following bacterial infection is principally involved in regulating lung inflammation in CF. NFκB regulates the transcription of several genes that are involved in inflammation, anti-apoptosis and anti-microbial activity, and hyper-activation of this transcription factor leads to a potent inflammatory response. Thus, NFκB is a potential anti-inflammatory drug target in CF. Screening of several compounds from natural sources in an in vitro model of CF-related inflammation wherein NFκB is activated by filtrates of a clinically isolated strain of PA (PAF led us to Withaferin A (WFA, a steroidal lactone from the plant Withania Somnifera L. Dunal. Our data demonstrate that WFA blocks PAF-induced activation of NFκB as determined using reporter

  7. Inhibition of NFkappaB by the natural product Withaferin A in cellular models of Cystic Fibrosis inflammation.

    Science.gov (United States)

    Maitra, Rangan; Porter, Melissa A; Huang, Shan; Gilmour, Brian P

    2009-05-13

    Cystic Fibrosis (CF) is one of the most common autosomal genetic disorders in humans. This disease is caused by mutations within a single gene, coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The phenotypic hallmark of CF is chronic lung infection and associated inflammation from opportunistic microbes such as Pseudomonas aeruginosa (PA), Haemophilus influenzae, and Staphylococcus aureus. This eventually leads to deterioration of lung function and death in most CF patients. Unfortunately, there is no approved therapy for correcting the genetic defect causal to the disease. Hence, controlling inflammation and infection in CF patients are critical to disease management. Accordingly, anti-inflammatory agents and antibiotics are used to manage chronic inflammation and infection in CF patients. However, most of the anti-inflammatory agents in CF have severe limitations due to adverse side effects, and resistance to antibiotics is becoming an even more prominent problem. Thus, new agents that can be used to control chronic inflammation in CF are needed in the absence of a cure for the disease. Activation of the transcription factor NFkappaB through Toll-like receptors (TLR) following bacterial infection is principally involved in regulating lung inflammation in CF. NFkappaB regulates the transcription of several genes that are involved in inflammation, anti-apoptosis and anti-microbial activity, and hyper-activation of this transcription factor leads to a potent inflammatory response. Thus, NFkappaB is a potential anti-inflammatory drug target in CF. Screening of several compounds from natural sources in an in vitro model of CF-related inflammation wherein NFkappaB is activated by filtrates of a clinically isolated strain of PA (PAF) led us to Withaferin A (WFA), a steroidal lactone from the plant Withania Somnifera L. Dunal. Our data demonstrate that WFA blocks PAF-induced activation of NFkappaB as determined using reporter assays, IL

  8. Low-fat yogurt consumption reduces biomarkers of chronic inflammation and inhibits markers of endotoxin exposure in healthy premenopausal women: a randomised controlled trial.

    Science.gov (United States)

    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.

  9. 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

  10. WNT signaling pathway gene polymorphisms and risk of hepatic fibrosis and inflammation in HCV-infected patients.

    Directory of Open Access Journals (Sweden)

    Yanhong Liu

    Full Text Available Chronic hepatitis C infection is the leading cause of hepatocellular carcinoma (HCC, a highly lethal malignancy with rapidly increasing prevalence in the United States. Little is known about genetic variations and HCC risk. This study aimed to determine if genetic variation in Wnt signaling pathway genes are associated with advanced hepatic fibrosis and inflammation risk in a hepatitis C virus (HCV infected population.We performed a genetic association cross-sectional study evaluating single nucleotide polymorphisms (SNPs in 58 candidate genes and risk of FibroSURE-Acti Test determined advanced fibrosis (F3/F4-F4 advanced cases vs. F0-F3 mild controls and inflammation (A2/A3-A3 advanced cases vs. A0-A2 mild controls. We calculated odds ratios (ORs and 95% confidence intervals (CIs employing multivariate logistic regression. Haplotypes were inferred by the HAPLO.STAT program, interactions were evaluated using multifactor dimensionality reduction (MDR analysis.Among 425 chronically HCV-infected male veterans, 155 (37% had advanced fibrosis and 180 (42% had advanced inflammation. Of 3016 SNPs evaluated, eight were significantly associated with fibrosis risk (e.g., SFRP2 rs11937424: OR = 2.19, 95% CI 1.48-3.23, P = 0.00004, and seven were significantly associated with inflammation risk (e.g., SFRP1 rs16890282: OR = 2.15, 95% CI 1.39-3.16, P = 0.0004. MDR analysis identified overweight/obese, SOST rs1405952, SFRP2 rs11937424, and FZD4 rs11234870 as the best interaction model for predicting risk of fibrosis; whereas race/ethnicity, FZD1 rs1346665, and TBX3 rs1520177 as the best interaction model for predicting risk of inflammation.Polymorphisms in several genes involved in the Wnt signaling pathway were associated with hepatic fibrosis or inflammation risk in HCV-infected males. Additional studies in other multi-ethnic HCV cohorts are needed to validate our findings in males and to assess if similar associations exist in chronically HCV

  11. Insight in modulation of inflammation in response to diclofenac intervention: a human intervention study

    NARCIS (Netherlands)

    van Erk, M.J.; Wopereis, S.; Rubingh, C.; van Vliet, T.; Verheij, E.; Cnubben, N.H.P.; Pedersen, T.L.; Newman, J.W.; Smilde, A.K.; van der Greef, J.; Hendriks, H.F.J.; van Ommen, B.

    2010-01-01

    Background: Chronic systemic low-grade inflammation in obese subjects is associated with health complications including cardiovascular diseases, insulin resistance and diabetes. Reducing inflammatory responses may reduce these risks. However, available markers of inflammatory status inadequately

  12. 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.

  13. Proximal Neuropathy and Associated Skeletal Muscle Changes Resembling Denervation Atrophy in Hindlimbs of Chronic Hypoglycaemic Rats

    DEFF Research Database (Denmark)

    Jensen, Vivi F.H.; Molck, Anne Marie; Soeborg, Henrik

    2017-01-01

    Peripheral neuropathy is one of the most common complications of diabetic hyperglycaemia. Insulin-induced hypoglycaemia (IIH) might potentially exacerbate or contribute to neuropathy as hypoglycaemia also causes peripheral neuropathy. In rats, IIH induces neuropathy associated with skeletal muscle......, and severity of the myofibre atrophy correlated with severity of axonal degeneration in sciatic nerve. Both neuropathy and myopathy were still present after four weeks of recovery, although the neuropathy was less severe. In conclusion, the results suggest that peripheral neuropathy induced by IIH progresses...... changes. Aims of this study were to investigate the progression and sequence of histopathologic changes caused by chronic IIH in rat peripheral nerves and skeletal muscle, and whether such changes were reversible. Chronic IIH was induced by infusion of human insulin, followed by an infusion-free recovery...

  14. Proximal Neuropathy and Associated Skeletal Muscle Changes Resembling Denervation Atrophy in Hindlimbs of Chronic Hypoglycaemic Rats

    DEFF Research Database (Denmark)

    Jensen, Vivi F.H.; Molck, Anne Marie; Soeborg, Henrik

    2018-01-01

    Peripheral neuropathy is one of the most common complications of diabetic hyperglycaemia. Insulin-induced hypoglycaemia (IIH) might potentially exacerbate or contribute to neuropathy as hypoglycaemia also causes peripheral neuropathy. In rats, IIH induces neuropathy associated with skeletal muscle......, and severity of the myofibre atrophy correlated with severity of axonal degeneration in sciatic nerve. Both neuropathy and myopathy were still present after four weeks of recovery, although the neuropathy was less severe. In conclusion, the results suggest that peripheral neuropathy induced by IIH progresses...... changes. Aims of this study were to investigate the progression and sequence of histopathologic changes caused by chronic IIH in rat peripheral nerves and skeletal muscle, and whether such changes were reversible. Chronic IIH was induced by infusion of human insulin, followed by an infusion-free recovery...

  15. Periodontal inflammation in relation to cognitive function in an older adult danish population

    DEFF Research Database (Denmark)

    Kamer, Angela R; Morse, Douglas E; Holm-Pedersen, Poul

    2012-01-01

    Inflammation plays a significant role in Alzheimer's disease (AD) pathogenesis. Studies have shown that systemic, peripheral infections affect AD patients. Cognitive dysfunction is a consistent finding in AD and periodontal disease is a chronic, peripheral infection often resulting in tooth loss....... We hypothesized that older adults with periodontal inflammation (PI) or many missing teeth would show impaired cognition compared to subjects without PI or with few missing teeth, and among subjects with PI, those with many missing teeth would show impaired cognition compared to those with few...

  16. Resveratrol Neuroprotection in a Chronic Mouse Model of Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Zoe eFonseca-Kelly

    2012-05-01

    Full Text Available Resveratrol is a naturally-occurring polyphenol that activates SIRT1, an NAD-dependent deacetylase. SRT501, a pharmaceutical formulation of resveratrol with enhanced systemic absorption, prevents neuronal loss without suppressing inflammation in mice with relapsing experimental autoimmune encephalomyelitis (EAE, a model of multiple sclerosis. In contrast, resveratrol has been reported to suppress inflammation in chronic EAE, although neuroprotective effects were not evaluated. The current studies examine potential neuroprotective and immunomodulatory effects of resveratrol in chronic EAE induced by immunization with myelin oligodendroglial glycoprotein peptide in C57/Bl6 mice. Effects of two distinct formulations of resveratrol administered daily orally were compared. Resveratrol delayed the onset of EAE compared to vehicle-treated EAE mice, but did not prevent or alter the phenotype of inflammation in spinal cords or optic nerves. Significant neuroprotective effects were observed, with higher numbers of retinal ganglion cells found in eyes of resveratrol-treated EAE mice with optic nerve inflammation. Results demonstrate that resveratrol prevents neuronal loss in this chronic demyelinating disease model, similar to its effects in relapsing EAE. Differences in immunosuppression compared with prior studies suggest that immunomodulatory effects may be limited and may depend on specific immunization parameters or timing of treatment. Importantly, neuroprotective effects can occur without immunosuppression, suggesting a potential additive benefit of resveratrol in combination with anti-inflammatory therapies for multiple sclerosis.

  17. 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

  18. 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...

  19. Physical inactivity and obesity: relation to asthma and chronic obstructive pulmonary disease?

    Science.gov (United States)

    ten Hacken, Nick H T

    2009-12-01

    Physical inactivity and obesity are modifiable risk factors for many chronic diseases, including cardiovascular disease, diabetes mellitus, osteoporosis, osteoarthritis, and depression. Both physical inactivity and obesity are associated with low-grade systemic inflammation that may contribute to the inflammatory processes present in many chronic diseases. In asthma, almost no studies are available in which physical inactivity has been studied using performance-based instruments. In contrast, the association between obesity and a higher prevalence of asthma has often been suggested in a large number of studies. In chronic obstructive pulmonary disease (COPD) physical inactivity has been demonstrated in a few studies that used performance-based instruments; this was associated with the higher COPD Global Initiative on Obstructive Lung Disease (GOLD) stages and a higher degree of systemic inflammation, independent of body mass index. In contrast to physical inactivity, obesity in COPD is associated with the lower GOLD stages. Additionally, obesity is associated with the chronic obstructive phenotype and features of the metabolic syndrome. To elucidate the independent relation of physical inactivity and obesity with systemic inflammation, performance-based studies of physical inactivity in asthma and COPD are highly needed.

  20. 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.

  1. Pareidolia in Neuroendocrinology: A Pituitary Macroadenoma Resembling "Big Bird".

    Science.gov (United States)

    de Herder, Wouter W

    2016-04-01

    The MRI picture of a pituitary macroadenoma with supra- and perisellar expansion resembled a famous character from a children's television series demonstrating that pareidolia is also observed in neuro-endocrinology and -radiology.

  2. 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.

  3. Preclinical Cancer Chemoprevention Studies Using Animal Model of Inflammation-Associated Colorectal Carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, Takuji [Cytopatholgy Division, Tohkai Cytopathology Institute, Cancer Research and Prevention (TCI-CaRP), 5-1-2 Minami-uzura, Gifu 500-8285 (Japan); Department of Tumor Pathology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194 (Japan)

    2012-07-16

    Inflammation is involved in all stages of carcinogenesis. Inflammatory bowel disease, such as ulcerative colitis and Crohn’s disease is a longstanding inflammatory disease of intestine with increased risk for colorectal cancer (CRC). Several molecular events involved in chronic inflammatory process are reported to contribute to multi-step carcinogenesis of CRC in the inflamed colon. They include over-production of free radicals, reactive oxygen and nitrogen species, up-regulation of inflammatory enzymes in arachidonic acid biosynthesis pathway, up-regulation of certain cytokines, and intestinal immune system dysfunction. In this article, firstly I briefly introduce our experimental animal models where colorectal neoplasms rapidly develop in the inflamed colorectum. Secondary, data on preclinical cancer chemoprevention studies of inflammation-associated colon carcinogenesis by morin, bezafibrate, and valproic acid, using this novel inflammation-related colorectal carcinogenesis model is described.

  4. Identification of novel anti-inflammatory agents from Ayurvedic medicine for prevention of chronic diseases: "reverse pharmacology" and "bedside to bench" approach.

    Science.gov (United States)

    Aggarwal, Bharat B; Prasad, Sahdeo; Reuter, Simone; Kannappan, Ramaswamy; Yadev, Vivek R; Park, Byoungduck; Kim, Ji Hye; Gupta, Subash C; Phromnoi, Kanokkarn; Sundaram, Chitra; Prasad, Seema; Chaturvedi, Madan M; Sung, Bokyung

    2011-10-01

    Inflammation, although first characterized by Cornelius Celsus, a physician in first Century Rome, it was Rudolf Virchow, a German physician in nineteenth century who suggested a link between inflammation and cancer, cardiovascular diseases, diabetes, pulmonary diseases, neurological diseases and other chronic diseases. Extensive research within last three decades has confirmed these observations and identified the molecular basis for most chronic diseases and for the associated inflammation. The transcription factor, Nuclear Factor-kappaB (NF-kappaB) that controls over 500 different gene products, has emerged as major mediator of inflammation. Thus agents that can inhibit NF-kappaB and diminish chronic inflammation have potential to prevent or delay the onset of the chronic diseases and further even treat them. In an attempt to identify novel anti-inflammatory agents which are safe and effective, in contrast to high throughput screen, we have turned to "reverse pharmacology" or "bed to benchside" approach. We found that Ayurveda, a science of long life, almost 6,000 years old, can serve as a "goldmine" for novel anti-inflammatory agents used for centuries to treat chronic diseases. The current review is an attempt to provide description of various Ayurvedic plants currently used for treatment, their active chemical components, and the inflammatory pathways that they inhibit.

  5. Correlation of MCP-4 and high-sensitivity C-reactive protein as a marker of inflammation in obesity and chronic periodontitis.

    Science.gov (United States)

    Pradeep, A R; Kumari, Minal; Kalra, Nitish; Priyanka, N

    2013-03-01

    Obesity is increasing in prevalence worldwide and has emerged as a strong risk factor for periodontal disease. Conversely, the remote effects of periodontal disease on various systemic diseases have been proposed. The aim of this study is to determine the presence of MCP-4 and high sensitivity C reactive protein (hsCRP) levels in gingival crevicular fluid (GCF) and serum in obese and non-obese subjects with chronic periodontitis and to find a correlation between MCP-4 and hsCRP in GCF and serum. Forty subjects (20 males and 20 females) were selected and divided into four groups (10 subjects in each group), based on clinical parameters: group NOH (non-obese healthy), group OH (obese healthy), Group NOCP (non-obese with chronic periodontitis) and group OCP (obese with chronic periodontitis). The levels of serum and GCF MCP-4 were determined by ELISA and hsCRP levels were determined by immunoturbidimetry method. The mean GCF and serum concentration of MCP-4 was highest for group OCP followed by group NOCP, group OH (in GCF); group OH, group NOCP(in serum) and least in group NOH. The mean hsCRP concentration was highest for group OCP followed by group OH, group NOCP and group NOH. A significant positive correlation was found between serum and GCF MCP-4 and hsCRP levels. GCF MCP-4 concentrations increased in periodontal disease compared to health and correlated positively with the severity of disease indicating it as a novel marker of periodontal disease. The serum concentration of MCP-4 was found to be more in obese group as compared to nonobese group indicating it as a marker of obesity. Furthermore, based on the positive correlation of MCP-4 and hsCRP found in this study, it can be proposed that MCP-4 and hsCRP may be the markers linking chronic inflammation in obesity and periodontal disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Mediterranean diet and low-grade subclinical inflammation: the Moli-sani study.

    Science.gov (United States)

    Bonaccio, Marialaura; Cerletti, Chiara; Iacoviello, Licia; de Gaetano, Giovanni

    2015-01-01

    Low-grade chronic inflammation is an underlying pathophysiological mechanism linking risk factors and/or metabolic disorders to increased risk of chronic degenerative disease. A meat-based pattern, as the Western type diet, is positively linked to higher levels of some important biomarkers of inflammation, such as C-reactive protein (CRP), interleukin-6 and fibrinogen. Conversely, a Mediterranean-like eating behavior is associated with lower degree of these biomarkers thus suggesting an anti-inflammatory action of its main food components. This chapter goes through the most important investigations addressing the relationship between dietary habits and subclinical inflammation. Attention was focussed on the findings from the Moli-sani study: this is a large prospective cohort study that recruited 24,325 men and women from the general population of the Molise Region, a Southern Italian area, with the aim of investigating genetic and environmental risk/protection factors for cardiovascular and tumor disease. For the first time, the Moli-sani study carefully investigated the Mediterranean diet as an environmental determinant of both platelet and white blood cell counts, starting from the hypothesis that a diet rich in healthy compounds could favorably influence the production and/or the clearance of these two cellular biomarkers of lowgrade inflammation. Additionally, evidence from this large Italian cohort showed that a Mediterranean-like diet was closely associated with relatively lower values of glucose, lipids, CRP, blood pressure and 10-year cardiovascular risk, while the consumption of healthy foods with high rather than low content in antioxidant vitamins and phytochemicals was associated with lower blood pressure and CRP plasma levels at least in men.

  7. Differential Effects of Acute (Extenuating and Chronic (Training Exercise on Inflammation and Oxidative Stress Status in an Animal Model of Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Edite Teixeira de Lemos

    2011-01-01

    Full Text Available This study compares the effects of a single bout of exercise (acute extenuating with those promoted by an exercise training program (chronic, focusing on low-grade chronic inflammation profile and on oxidative stress status, using the obese ZDF rats as a model of type 2 diabetes mellitus (T2DM. Animals were sacrificed after 12 weeks of a swimming training program and after a single bout of acute extenuating exercise. Glycaemic, insulinemic, and lipidic profile (triglycerides, total-cholesterol were evaluated, as well as inflammatory (serum CRPhs, TNF-α, adiponectin and oxidative (lipidic peroxidation and uric acid status. When compared to obese diabetic sedentary rats, the animals submitted to acute exercise presented significantly lower values of glycaemia and insulinaemia, with inflammatory profile and oxidative stress significantly aggravated. The trained animals showed amelioration of glycaemic and lipidic dysmetabolism, accompanied by remarkable reduction of inflammatory and oxidative markers. In conclusion, the results presented herein suggessted that exercise pathogenesis-oriented interventions should not exacerbate underlying inflammatory stress associated with T2DM.

  8. Fathers see stronger family resemblances than non-fathers in unrelated children's faces.

    Science.gov (United States)

    Bressan, Paola; Dal Pos, Stefania

    2012-12-01

    Even after they have taken all reasonable measures to decrease the probability that their spouses cheat on them, men still face paternal uncertainty. Such uncertainty can lead to paternal disinvestment, which reduces the children's probability to survive and reproduce, and thus the reproductive success of the fathers themselves. A theoretical model shows that, other things being equal, men who feel confident that they have fathered their spouses' offspring tend to enjoy greater fitness (i.e., leave a larger number of surviving progeny) than men who do not. This implies that fathers should benefit from exaggerating paternal resemblance. We argue that the self-deceiving component of this bias could be concealed by generalizing this resemblance estimation boost to (1) family pairs other than father-child and (2) strangers. Here, we tested the prediction that fathers may see, in unrelated children's faces, stronger family resemblances than non-fathers. In Study 1, 70 men and 70 women estimated facial resemblances between children paired, at three different ages (as infants, children, and adolescents), either to themselves or to their parents. In Study 2, 70 men and 70 women guessed the true parents of the same children among a set of adults. Men who were fathers reported stronger similarities between faces than non-fathers, mothers, and non-mothers did, but were no better at identifying childrens' real parents. We suggest that, in fathers, processing of facial resemblances is biased in a manner that reflects their (adaptive) wishful thinking that fathers and children are related.

  9. Added Sugar Consumption and Chronic Oral Disease Burden among Adolescents in Brazil.

    Science.gov (United States)

    Carmo, C D S; Ribeiro, M R C; Teixeira, J X P; Alves, C M C; Franco, M M; França, A K T C; Benatti, B B; Cunha-Cruz, J; Ribeiro, C C C

    2018-05-01

    Chronic oral diseases are rarely studied together, especially with an emphasis on their common risk factors. This study examined the association of added sugar consumption on "chronic oral disease burden" among adolescents, with consideration of obesity and systemic inflammation pathways through structural equation modeling. A cross-sectional study was conducted of a complex random sample of adolescent students enrolled at public schools in São Luís, Brazil ( n = 405). The outcome was chronic oral disease burden, a latent variable based on the presence of probing depth ≥4 mm, bleeding on probing, caries, and clinical consequences of untreated caries. The following hypotheses were tested: 1) caries and periodontal diseases among adolescents are correlated with each other; 2) added sugar consumption and obesity are associated with chronic oral disease burden; and 3) chronic oral disease burden is linked to systemic inflammation. Models were adjusted for socioeconomic status, added sugar consumption, oral hygiene behaviors, obesity, and serum levels of interleukin 6 (IL-6). All estimators of the latent variable chronic oral disease burden involved factor loadings ≥0.5 and P values disease burden values. Obesity was associated with high IL-6 levels (SC = 0.232, P = 0.001). Visible plaque index was correlated with chronic oral disease burden (SC = 0.381, P periodontal diseases are associated with each other and with added sugar consumption, obesity, and systemic inflammation reinforces the guidance of the World Health Organization that any approach intended to prevent noncommunicable diseases should be directed toward common risk factors.

  10. Glufosinate aerogenic exposure induces glutamate and IL-1 receptor dependent lung inflammation.

    Science.gov (United States)

    Maillet, Isabelle; Perche, Olivier; Pâris, Arnaud; Richard, Olivier; Gombault, Aurélie; Herzine, Ameziane; Pichon, Jacques; Huaux, Francois; Mortaud, Stéphane; Ryffel, Bernhard; Quesniaux, Valérie F J; Montécot-Dubourg, Céline

    2016-11-01

    Glufosinate-ammonium (GLA), the active component of an herbicide, is known to cause neurotoxicity. GLA shares structural analogy with glutamate. It is a powerful inhibitor of glutamine synthetase (GS) and may bind to glutamate receptors. Since these potentials targets of GLA are present in lung and immune cells, we asked whether airway exposure to GLA may cause lung inflammation in mice. A single GLA exposure (1 mg/kg) induced seizures and inflammatory cell recruitment in the broncho-alveolar space, and increased myeloperoxidase (MPO), inducible NO synthase (iNOS), interstitial inflammation and disruption of alveolar septae within 6-24 h. Interleukin 1β (IL-1β) was increased and lung inflammation depended on IL-1 receptor 1 (IL-1R1). We demonstrate that glutamate receptor pathway is central, since the N-methyl-D-aspartate (NMDA) receptor inhibitor MK-801 prevented GLA-induced lung inflammation. Chronic exposure (0.2 mg/kg 3× per week for 4 weeks) caused moderate lung inflammation and enhanced airway hyperreactivity with significant increased airway resistance. In conclusion, GLA aerosol exposure causes glutamate signalling and IL-1R-dependent pulmonary inflammation with airway hyperreactivity in mice. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

  11. 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.

  12. Omega-3-derived mediators counteract obesity-induced adipose tissue inflammation.

    Science.gov (United States)

    Titos, Esther; Clària, Joan

    2013-12-01

    Chronic low-grade inflammation in adipose tissue has been recognized as a key step in the development of obesity-associated complications. In obesity, the accumulation of infiltrating macrophages in adipose tissue and their phenotypic switch to M1-type dysregulate inflammatory adipokine production leading to obesity-linked insulin resistance. Resolvins are potent anti-inflammatory and pro-resolving mediators endogenously generated from omega-3 fatty acids that act as "stop-signals" of the inflammatory response promoting the resolution of inflammation. Recently, a deficit in the production of these endogenous anti-inflammatory signals has been demonstrated in obese adipose tissue. The restoration of their levels by either exogenous administration of these mediators or feeding omega-3-enriched diets, improves the inflammatory status of adipose tissue and ameliorates metabolic dysfunction. Here, we review the current knowledge on the role of these endogenous autacoids in the resolution of adipose tissue inflammation with special emphasis on their functional actions on macrophages. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Comparison of 18F-fluoromethylcholine and 2-deoxy-D-glucose in the distribution of tumor and inflammation

    International Nuclear Information System (INIS)

    Kubota, Kazuo; Furumoto, Shozo; Iwata, Ren; Fukuda, Hiroshi; Kawamura, Kazunori; Ishiwata, Kiichi

    2006-01-01

    The distribution characteristics of 18 F-fluoromethylcholine ( 18 F-choline) in tumor and inflammatory tissue were compared with those of 14 C or 3 H-2-deoxyglucose (2DG) as a substitute for fluorodeoxyglucose (FDG). A solid tumor model of AH109A in the back of Donryu rats and an aseptic inflammation model of turpentine oil injection subcutaneously in rats were used for experiments. Tissue distribution was examined at 5, 30 and 60 min after injection of a mixture of 18 F-choline and 3 H-2DG. Double-tracer high-resolution autoradiographs (ARGs) of tumor and inflammation were obtained using 18 F-choline and 14 C-2DG. Whole body (WB) ARG was performed with 18 F-choline. Tumor uptake of 18 F-choline reached a peak at 30 min, when the tumor to blood ratio was 5.1. Both tumor and inflammation uptake of 2DG were higher than those of 18 F-choline. 18 F-choline uptake by inflammation was lower than that by tumor. The tumor to brain uptake ratio was 5.7 with 18 F-choline and 1.2 with 2DG. In the ARG of inflammation, linear or ring-like structures of 2DG uptake were observed in the wall of the abscess, but were not identified with 18 F-choline. Photomicrography showed that the uptake was limited to granulocytes, macrophages and fibroblasts, consistent with sub-acute or chronic inflammation. 18 F-choline uptake by inflammation was lower than that of 2DG in the tissue distribution study, and 18 F-choline uptake by abscess wall was significantly lower than that of 2DG in the autoradiography study. Our results may suggest the feasibility of 18 F-choline-PET imaging for the differential diagnosis of cancer and chronic inflammation in lung and brain. (author)

  14. Functional role of CCL5/RANTES for HCC progression during chronic liver disease

    NARCIS (Netherlands)

    Mohs, Antje; Kuttkat, Nadine; Reissing, Johanna; Zimmermann, Henning Wolfgang; Sonntag, Roland; Proudfoot, Amanda; Youssef, Sameh A.; de Bruin, Alain; Cubero, Francisco Javier; Trautwein, Christian

    Background & Aims: During liver inflammation, triggering fibrogenesis and carcinogenesis immune cells play a pivotal role. In the present study we investigated the role of CCL5 in human and in murine models of chronic liver inflammation leading to hepatocellular carcinoma (HCC) development. Methods:

  15. Hepatocyte Toll-like receptor 4 regulates obesity-induced inflammation and insulin resistance

    Science.gov (United States)

    Chronic low-grade inflammation is a hallmark of obesity and thought to contribute to the development of obesity-related insulin resistance. Toll-like receptor 4 (Tlr4) is a key mediator of pro-inflammatory responses. Mice lacking Tlr4s are protected from diet-induced insulin resistance and inflammat...

  16. Effects of pregnancy on obesity-induced inflammation in a mouse model of fetal programming

    DEFF Research Database (Denmark)

    Ingvorsen, Camilla; Thysen, Anna Hammerich; Fernandez-Twinn, D.

    2014-01-01

    Objective Maternal obesity is associated with increased risk of metabolic dysfunction in the offspring. It is not clear whether it is the metabolic changes or chronic low-grade inflammation in the obese state that causes this metabolic programming. We therefore investigated whether low-grade infl......Objective Maternal obesity is associated with increased risk of metabolic dysfunction in the offspring. It is not clear whether it is the metabolic changes or chronic low-grade inflammation in the obese state that causes this metabolic programming. We therefore investigated whether low...... of the obese animals, which suggested that monocytes are being recruited from the blood to the liver and adipose tissue in the obese animals. Gestation reversed macrophage infiltration, such that obese dams showed a lower adipose tissue macrophage count at the end of gestation compared to pre-pregnancy obese...

  17. Association of six CpG-SNPs in the inflammation-related genes with coronary heart disease

    OpenAIRE

    Chen, Xiaomin; Chen, Xiaoying; Xu, Yan; Yang, William; Wu, Nan; Ye, Huadan; Yang, Jack Y.; Hong, Qingxiao; Xin, Yanfei; Yang, Mary Qu; Deng, Youping; Duan, Shiwei

    2016-01-01

    Background Chronic inflammation has been widely considered to be the major risk factor of coronary heart disease (CHD). The goal of our study was to explore the possible association with CHD for inflammation-related single nucleotide polymorphisms (SNPs) involved in cytosine-phosphate-guanine (CpG) dinucleotides. A total of 784 CHD patients and 739 non-CHD controls were recruited from Zhejiang Province, China. Using the Sequenom MassARRAY platform, we measured the genotypes of six inflammatio...

  18. Liver immunology and its role in inflammation and homeostasis.

    Science.gov (United States)

    Robinson, Mark W; Harmon, Cathal; O'Farrelly, Cliona

    2016-05-01

    The human liver is usually perceived as a non-immunological organ engaged primarily in metabolic, nutrient storage and detoxification activities. However, we now know that the healthy liver is also a site of complex immunological activity mediated by a diverse immune cell repertoire as well as non-hematopoietic cell populations. In the non-diseased liver, metabolic and tissue remodeling functions require elements of inflammation. This inflammation, in combination with regular exposure to dietary and microbial products, creates the potential for excessive immune activation. In this complex microenvironment, the hepatic immune system tolerates harmless molecules while at the same time remaining alert to possible infectious agents, malignant cells or tissue damage. Upon appropriate immune activation to challenge by pathogens or tissue damage, mechanisms to resolve inflammation are essential to maintain liver homeostasis. Failure to clear 'dangerous' stimuli or regulate appropriately activated immune mechanisms leads to pathological inflammation and disrupted tissue homeostasis characterized by the progressive development of fibrosis, cirrhosis and eventual liver failure. Hepatic inflammatory mechanisms therefore have a spectrum of roles in the healthy adult liver; they are essential to maintain tissue and organ homeostasis and, when dysregulated, are key drivers of the liver pathology associated with chronic infection, autoimmunity and malignancy. In this review, we explore the changing perception of inflammation and inflammatory mediators in normal liver homeostasis and propose targeting of liver-specific immune regulation pathways as a therapeutic approach to treat liver disease.

  19. Evidence for chronic inflammation as a component of the interstitial lung disease associated with progressive systemic sclerosis

    International Nuclear Information System (INIS)

    Rossi, G.A.; Bitterman, P.B.; Rennard, S.I.; Ferrans, V.J.; Crystal, R.G.

    1985-01-01

    Progressive systemic sclerosis (PSS) is a generalized disorder characterized by fibrosis of many organs including the lung parenchyma. Unlike most other interstitial disorders, traditional concepts of the interstitial lung disease associated with PSS have held it to be a ''pure'' fibrotic disorder without a significant inflammatory component. To directly evaluate whether an active alveolitis is associated with this disorder, patients with chronic interstitial lung disease and PSS were studied by open lung biopsy, gallium-67 scanning, and bronchoalveolar lavage. Histologic evaluation of the biopsies demonstrated that the interstitial fibrosis of PSS is clearly associated with the presence of macrophages, lymphocytes, and polymorphonuclear leukocytes, both in the interstitium and on the alveolar epithelial surface. Gallium-67 scans were positive in 77% of the patients, showing diffuse, primarily lower zone uptake, suggestive of active inflammation. Consistent with the histologic findings, bronchoalveolar lavage studies demonstrated a mild increase in the proportions of neutrophils and eosinophils with occasional increased numbers of lymphocytes. Importantly, alveolar macrophages from patients with PSS showed increased release of fibronectin and alveolar-macrophage-derived growth factor, mediators that together stimulate lung fibroblasts to proliferate, thus suggesting at least one mechanism modulating the lung fibrosis of these patients

  20. Short-course oral steroids as an adjunct therapy for chronic rhinosinusitis

    NARCIS (Netherlands)

    Head, Karen; Chong, Lee Yee; Hopkins, Claire; Philpott, Carl; Schilder, Anne G M; Burton, Martin J

    2016-01-01

    BACKGROUND: This review is one of a suite of six Cochrane reviews looking at the primary medical management options for patients with chronic rhinosinusitis.Chronic rhinosinusitis is a common condition involving inflammation of the lining of the nose and paranasal sinuses. It is characterised by

  1. High-fat diet-induced adiposity, adipose inflammation, hepatic steatosis and hyperinsulinemia in outbred CD-1 mice.

    Directory of Open Access Journals (Sweden)

    Mingming Gao

    Full Text Available High-fat diet (HFD has been applied to a variety of inbred mouse strains to induce obesity and obesity related metabolic complications. In this study, we determined HFD induced development of metabolic disorders on outbred female CD-1 mice in a time dependent manner. Compared to mice on regular chow, HFD-fed CD-1 mice gradually gained more fat mass and consequently exhibited accelerated body weight gain, which was associated with adipocyte hypertrophy and up-regulated expression of adipose inflammatory chemokines and cytokines such as Mcp-1 and Tnf-α. Increased fat accumulation in white adipose tissue subsequently led to ectopic fat deposition in brown adipose tissue, giving rise to whitening of brown adipose tissue without altering plasma level of triglyceride. Ectopic fat deposition was also observed in the liver, which was associated with elevated expression of key genes involved in hepatic lipid sequestration, including Ppar-γ2, Cd36 and Mgat1. Notably, adipose chronic inflammation and ectopic lipid deposition in the liver and brown fat were accompanied by glucose intolerance and insulin resistance, which was correlated with hyperinsulinemia and pancreatic islet hypertrophy. Collectively, these results demonstrate sequentially the events that HFD induces physiological changes leading to metabolic disorders in an outbred mouse model more closely resembling heterogeneity of the human population.

  2. Kaempferol and inflammation: From chemistry to medicine.

    Science.gov (United States)

    Devi, Kasi Pandima; Malar, Dicson Sheeja; Nabavi, Seyed Fazel; Sureda, Antoni; Xiao, Jianbo; Nabavi, Seyed Mohammad; Daglia, Maria

    2015-09-01

    Inflammation is an important process of human healing response, wherein the tissues respond to injuries induced by many agents including pathogens. It is characterized by pain, redness and heat in the injured tissues. Chronic inflammation seems to be associated with different types of diseases such as arthritis, allergies, atherosclerosis, and even cancer. In recent years natural product based drugs are considered as the novel therapeutic strategy for prevention and treatment of inflammatory diseases. Among the different types of phyto-constituents present in natural products, flavonoids which occur in many vegetable foods and herbal medicines are considered as the most active constituent, which has the potency to ameliorate inflammation under both in vitro and in vivo conditions. Kaempferol is a natural flavonol present in different plant species, which has been described to possess potent anti-inflammatory properties. Despite the voluminous literature on the anti-inflammatory effects of kaempferol, only very limited review articles has been published on this topic. Hence the present review is aimed to provide a critical overview on the anti-inflammatory effects and the mechanisms of action of kaempferol, based on the current scientific literature. In addition, emphasis is also given on the chemistry, natural sources, bioavailability and toxicity of kaempferol. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. The resolution of inflammation: Principles and challenges.

    Science.gov (United States)

    Headland, Sarah E; Norling, Lucy V

    2015-05-01

    The concept that chemokines, cytokines and pro-inflammatory mediators act in a co-ordinated fashion to drive the initiation of the inflammatory reaction is well understood. The significance of such networks acting during the resolution of inflammation however is poorly appreciated. In recent years, specific pro-resolving mediators were discovered which activate resolution pathways to return tissues to homeostasis. These mediators are diverse in nature, and include specialized lipid mediators (lipoxins, resolvins, protectins and maresins) proteins (annexin A1, galectins) and peptides, gaseous mediators including hydrogen sulphide, a purine (adenosine), as well as neuromodulator release under the control of the vagus nerve. Functionally, they can act to limit further leukocyte recruitment, induce neutrophil apoptosis and enhance efferocytosis by macrophages. They can also switch macrophages from classical to alternatively activated cells, promote the return of non-apoptotic cells to the lymphatics and help initiate tissue repair mechanisms and healing. Within this review we highlight the essential cellular aspects required for successful tissue resolution, briefly discuss the pro-resolution mediators that drive these processes and consider potential challenges faced by researchers in the quest to discover how inflammation resolves and why chronic inflammation persists. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Differential expression of interleukin-32 in chronic rhinosinusitis with and without nasal polyps

    NARCIS (Netherlands)

    Keswani, A.; Chustz, R.T.; Suh, L.; Carter, R.; Peters, A.T.; Tan, B.K.; Chandra, R.; Kim, S.H.; Azam, T.; Dinarello, C.A.; Kern, R.C.; Schleimer, R.P.; Kato, A.

    2012-01-01

    BACKGROUND: Chronic rhinosinusitis (CRS) is a heterogeneous disease characterized by local inflammation of the upper airways and sinuses and is frequently divided into polypoid CRS (CRSwNP) and nonpolypoid CRS (CRSsNP). However, the mechanism of inflammation in CRS has still not been fully

  5. [Technological advances and micro-inflammation in dialysis patients].

    Science.gov (United States)

    Ferro, Giuseppe; Ravaglia, Fiammetta; Ferrari, Elisa; Romoli, Elena; Michelassi, Stefano; Caiani, David; Pizzarelli, Francesco

    2015-01-01

    As currently performed, on line hemodiafiltration reduces, but does not normalize, the micro-inflammation of uremic patients. Recent technological advances make it possible to further reduce the inflammation connected to the dialysis treatment. 
Short bacterial DNA fragments are pro-inflammatory and can be detected in the dialysis fluids. However, their determination is not currently within normal controls of the quality of the dialysate. The scenario may change once the analysis of these fragments yields reliable, inexpensive, quick and easy to evaluate the results. At variance with standard bicarbonate dialysate, Citrate dialysate induces far less inflammation both for the well-known anti-inflammatory effect of such buffer and also because it is completely acetate free, e.g. a definitely pro-inflammatory buffer. However, the extensive use of citrate dialysate in chronic dialysis is prevented because of concerns about its potential calcium lowering effect. In our view, high convective exchange on line hemodiafiltration performed with dialysate, whose sterility and a-pirogenicity is guaranteed by increasingly sophisticated controls and with citrate buffer whose safety is certified, can serve as the gold standard of dialysis treatments in future.

  6. Mucosal T cells in gut homeostasis and inflammation

    OpenAIRE

    van Wijk, Femke; Cheroutre, Hilde

    2010-01-01

    The antigen-rich environment of the gut interacts with a highly integrated and specialized mucosal immune system that has the challenging task of preventing invasion and the systemic spread of microbes, while avoiding excessive or unnecessary immune responses to innocuous antigens. Disruption of the mucosal barrier and/or defects in gut immune regulatory networks may lead to chronic intestinal inflammation as seen in inflammatory bowel disease. The T-cell populations of the intestine play a c...

  7. DsbA-L prevents obesity-induced inflammation and insulin resistance by suppressing the mtDNA release-activated cGAS-cGAMP-STING pathway

    Science.gov (United States)

    Chronic inflammation in adipose tissue plays a key role in obesity-induced insulin resistance. However, the mechanisms underlying obesity-induced inflammation remain elusive. Here we show that obesity promotes mtDNA release into the cytosol, where it triggers inflammatory responses by activating the...

  8. Airway hyperresponsiveness in chronic obstructive pulmonary disease : A marker of asthma-chronic obstructive pulmonary disease overlap syndrome?

    NARCIS (Netherlands)

    Tkacova, Ruzena; Dai, Darlene L. Y.; Vonk, Judith M.; Leung, Janice M.; Hiemstra, Pieter S.; van den Berge, Maarten; Kunz, Lisette; Hollander, Zsuzsanna; Tashkin, Donald; Wise, Robert; Connett, John; Ng, Raymond; McManus, Bruce; Man, S. F. Paul; Postma, Dirkje S.; Sin, Don D.

    2016-01-01

    Background: The impact of airway hyperreactivity (AHR) on respiratory mortality and systemic inflammation among patients with chronic obstructive pulmonary disease (COPD) is largely unknown. We used data from 2 large studies to determine the relationship between AHR and FEV1 decline, respiratory

  9. Esculetin from Fraxinus rhynchophylla attenuates atopic skin inflammation by inhibiting the expression of inflammatory cytokines.

    Science.gov (United States)

    Jeong, Na-Hee; Yang, Eun-Ju; Jin, Meiling; Lee, Jong Yeong; Choi, Young-Ae; Park, Pil-Hoon; Lee, Sang-Rae; Kim, Sun-Uk; Shin, Tae-Yong; Kwon, Taeg Kyu; Jang, Yong Hyun; Song, Kyung-Sik; Kim, Sang-Hyun

    2018-06-01

    Atopic dermatitis (AD) is a common chronic inflammatory skin disorder afflicting from infancy to adults with itching, scratching, and lichenification. We aimed to investigate the effects of esculetin from Fraxinus rhynchophylla on atopic skin inflammation. For induction of atopic skin inflammation, we exposed the ears of female BALB/c mice to house dust mite (Dermatophagoides farinae extract, DFE) and 2,4-dinitrochlorobenzene (DNCB) for 4 weeks. Oral administration of esculetin reduced the symptoms of DFE/DNCB-induced atopic skin inflammation, which were evaluated based on ear swelling and number of scratch bouts. The immunoglobulin (Ig) E, IgG2a, and histamine levels in serum were decreased and inflammatory cell infiltration in skin tissue was reduced by the esculetin. It suppressed production of Th1, Th2 and Th17-related cytokines such as tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-4, IL-13, IL-31 and IL-17 in the ear tissue. Furthermore, we investigated the effects of esculetin on activated keratinocytes, which are representative cells used for studying the pathogenesis of acute and chronic atopic skin inflammation. As results, esculetin suppressed gene expression of Th1, Th2 and Th17 cytokines and the activation of nuclear factor-κB and signal transducer and activator of transcription 1 in TNF-α/IFN-γ-stimulated keratinocytes. Taken together, these results imply that esculetin attenuated atopic skin inflammation, suggesting that esculetin could be a potential therapeutic candidate for the treatment of AD. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. The receptor RAGE: Bridging inflammation and cancer

    Directory of Open Access Journals (Sweden)

    Hess Jochen

    2009-05-01

    Full Text Available Abstract The receptor for advanced glycation end products (RAGE is a single transmembrane receptor of the immunoglobulin superfamily that is mainly expressed on immune cells, neurons, activated endothelial and vascular smooth muscle cells, bone forming cells, and a variety of cancer cells. RAGE is a multifunctional receptor that binds a broad repertoire of ligands and mediates responses to cell damage and stress conditions. It activates programs responsible for acute and chronic inflammation, and is implicated in a number of pathological diseases, including diabetic complications, stroke, atheriosclerosis, arthritis, and neurodegenerative disorders. The availability of Rage knockout mice has not only advanced our knowledge on signalling pathways within these pathophysiological conditions, but also on the functional importance of the receptor in processes of cancer. Here, we will summarize molecular mechanisms through which RAGE signalling contributes to the establishment of a pro-tumourigenic microenvironment. Moreover, we will review recent findings that provide genetic evidence for an important role of RAGE in bridging inflammation and cancer.

  11. Role of inflammation in the aging bones.

    Science.gov (United States)

    Abdelmagid, Samir M; Barbe, Mary F; Safadi, Fayez F

    2015-02-15

    Chronic inflammation in aging is characterized by increased inflammatory cytokines, bone loss, decreased adaptation, and defective tissue repair in response to injury. Aging leads to inherent changes in mesenchymal stem cell (MSC) differentiation, resulting in impaired osteoblastogenesis. Also, the pro-inflammatory cytokines increase with aging, leading to enhanced myelopoiesis and osteoclastogenesis. Bone marrow macrophages (BMMs) play pivotal roles in osteoblast differentiation, the maintenance of hematopoietic stem cells (HSCs), and subsequent bone repair. However, during aging, little is known about the role of macrophages in the differentiation and function of MSC and HSC. Aged mammals have higher circulating pro-inflammatory cytokines than young adults, supporting the hypothesis of increased inflammation with aging. This review will aid in the understanding of the potential role(s) of pro-inflammatory (M1) and anti-inflammatory (M2) macrophages in differentiation and function of osteoblasts and osteoclasts in relation to aging. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Perinatal programming of metabolic dysfunction and obesity-induced inflammation

    DEFF Research Database (Denmark)

    Ingvorsen, Camilla; Hellgren, Lars; Pedersen, Susanne Brix

    The number of obese women in the childbearing age is drastically increasing globally. As a consequence, more children are born by obese mothers. Unfortunately, maternal obesity and/ or high fat intake during pregnancy increase the risk of developing obesity, type-2 diabetes, cardiovascular disease...... and non-alcoholic fatty liver disease in the children, which passes obesity and metabolic dysfunction on from generation to generation. Several studies try to elucidate causative effects of maternal metabolic markers on the metabolic imprinting in the children; however diet induced obesity is also...... associated with chronic low grade inflammation. Nobody have yet investigated the role of this inflammatory phenotype, but here we demonst rate that obesity induced inflammation is reversed during pregnancy in mice, and is therefore less likely to affect the fetal programming of metabolic dysfunction. Instead...

  13. Malnutrition and its association with inflammation and vascular disease in children on maintenance dialysis.

    Science.gov (United States)

    Canpolat, Nur; Caliskan, Salim; Sever, Lale; Tasdemir, Mehmet; Ekmekci, Ozlem Balcı; Pehlivan, Gulseren; Shroff, Rukshana

    2013-11-01

    Malnutrition is associated with both inflammation and atherosclerotic cardiovascular disease in adults with chronic kidney disease. We studied the prevalence of malnutrition and its possible associations with inflammation and vascular disease in children on chronic dialysis. Thirty-three patients on maintenance dialysis (18 peritoneal dialysis, 15 hemodialysis) and 19 age- and gender- matched healthy controls were studied. Nutritional status was assessed by anthropometric measurements including body mass index (BMI), upper arm measurements, multifrequency bioimpedance analysis (BIA) and serum levels of albumin, prealbumin, and cholesterol. Inflammation was assessed by serum levels of C-reactive protein (CRP), interleukin (IL)-6, and tumor necrosis factor (TNF)-alpha. The carotid artery intima thickness (cIMT) was measured to assess vascular disease. Compared with healthy children, patients had lower anthropometric measurements (P Malnutrition was present in 8 (24%) and lower BIA-based fat mass was independently associated with higher IL-6 levels (P = 0.035). An increased cIMT was present in 16 (48.5%); however, there was no difference in cIMT-SDS between patients with and without malnutrition. Carotid IMT did not show any association with nutritional indices; but positively correlated with serum IL-6 (P = 0.037), CRP (P = 0.012), and iPTH (P = 0.009), and independently associated with only iPTH (P = 0.018). Children on dialysis are at an increased risk of malnutrition, inflammation, and vascular disease. Although each of these three conditions exists, there is no interaction among them all. We postulate that the malnutrition-inflammation-atherosclerosis (MIA) complex might not exist in pediatric dialysis patients.

  14. The effect of the competitive season in professional basketball on inflammation and iron metabolism.

    Science.gov (United States)

    Dzedzej, A; Ignatiuk, W; Jaworska, J; Grzywacz, T; Lipińska, P; Antosiewicz, J; Korek, A; Ziemann, E

    2016-09-01

    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(OH)D3) 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.

  15. The effect of the competitive season in professional basketball on inflammation and iron metabolism

    Science.gov (United States)

    Dzedzej, A; Ignatiuk, W; Jaworska, J; Grzywacz, T; Lipińska, P; Antosiewicz, J; Korek, A

    2016-01-01

    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(OH)D3) 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. PMID:27601776

  16. Histones link inflammation and thrombosis through the induction of Weibel-Palade body exocytosis.

    Science.gov (United States)

    Michels, A; Albánez, S; Mewburn, J; Nesbitt, K; Gould, T J; Liaw, P C; James, P D; Swystun, L L; Lillicrap, D

    2016-11-01

    Essentials Dysregulated DNA and histone release can promote pathological immunothrombosis. Weibel-Palade bodies (WPBs) are sentinel-like organelles that respond to proinflammatory stimuli. Histones induce WPB exocytosis in a caspase, calcium and charge-dependent mechanism. A targetable axis may exist between DNA/histones and WPBs in inflammation and immunothrombosis. Background Damage-associated molecular patterns (DAMPs), including molecules such as DNA and histones, are released into the blood following cell death. DAMPs promote a procoagulant phenotype through enhancement of thrombin generation and platelet activation, thereby contributing to immunothrombosis. Weibel-Palade bodies (WPBs) are dynamic endothelial cell organelles that contain procoagulant and proinflammatory mediators, such as von Willebrand factor (VWF), and are released in response to cell stresses. VWF mediates platelet adhesion and aggregation, and has been implicated as a procoagulant component of the innate immune response. Objective To determine the influence of histones and DNA on WPB release, and characterize their association in models of inflammation. Methods We treated C57BL/6J mice and cultured endothelial cells with histones (unfractionated, lysine-rich or arginine-rich) and DNA, and measured WPB exocytosis. We used inhibitors to determine a mechanism of histone-induced WPB release in vitro. We characterized the release of DAMPs and WPBs in response to acute and chronic inflammation in human and murine models. Results and conclusions Histones, but not DNA, induced the release of VWF (1.46-fold) from WBPs and caused thrombocytopenia (0.74-fold), which impaired arterial thrombus formation in mice. Histones induced WPB release from endothelial cells in a caspase-dependent, calcium-dependent and charge-dependent manner, and promoted platelet capture in a flow chamber model of VWF-platelet string formation. The levels of DAMPs and WPB-released proteins were elevated during inflammation

  17. Thyroid gland in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Miłkowska-Dymanowska, Joanna; Białas, Adam J; Laskowska, Paulina; Górski, Paweł; Piotrowski, Wojciech J

    2017-01-01

    The risk of chronic obstructive pulmonary disease (COPD), as well as thyroid diseases increases with age. COPD is a common systemic disease associated with chronic inflammation. Many endocrinological disorders, including thyroid gland diseases are related to systemic inflammation. Epidemiological studies suggest that patients with COPD are at higher risk of thyroid disorders. These associations are not well-studied and thyroid gland diseases are not included on the broadly acknowledged list of COPD comorbidities. They may seriously handicap quality of life of COPD patients. Unfortunately, the diagnosis may be difficult, as many signs are masked by the symptoms of the index disease. The comprehension of the correlation between thyroid gland disorders and COPD may contribute to better care of patients. In this review, we attempt to revise available literature describing existing links between COPD and thyroid diseases.

  18. [Airway oxidative stress and inflammation markers in chronic obstructive pulmonary diseases(COPD) patients are linked with exposure to traffic-related air pollution: a panel study].

    Science.gov (United States)

    Chen, J; Zhao, Q; Liu, B B; Wang, J; Xu, H B; Zhang, Y; Song, X M; He, B; Huang, W

    2016-05-01

    To investigate the effects of short-term exposure to traffic-related air pollution on airway oxidative stress and inflammation in chronic obstructive pulmonary diseases (COPD) patients. A panel of forty-five diagnosed COPD patients were recruited and followed with repeated measurements of biomarkers reflecting airway oxidative stress and inflammation in exhaled breath condensate (EBC), including nitrate and nitrite, 8-isoprostane, interleukin-8 and acidity of EBC (pH), between 5(th) September in 2014 and 26(th) May in 2015. The associations between air pollution and biomarkers were analyzed with mixed-effects models, controlling for confounding covariates. The concentration of PM2.5, black carbon, NO2 and number concentration of particles with diameter less than 100 nm (PNC100), and particles in size ranges between 100 nm to 200 nm (PNC100-200) during the first follow-up were (156.5±117.7), (10.7±0.7), (165.9±66.0)μg/m(3) and 397 521±96 712, 79 421±44 090 per cubic meter, respectively; the concentration were (67.9±29.6), (3.4±1.3), (126.1±10.9) μg/m(3) and (295 682±39 430), (24 693±12 369) per cubic meter, respectively during the second follow-up. The differences were of significance, with t value being 3.10, 4.42, 2.61, 4.02, 5.12, respectively and P value being 0.005,stress. For an IQR increase in PM2.5, black carbon and PNC100-200, respective increases of 0.17 ng/ml (95% CI: 0.02-0.33), 0.12 ng/ml (95% CI: 0.01-0.24) and 0.13 ng/ml (95% CI:0.02-0.24) in interleukin-8 in EBC reflecting airway inflammation were also observed. An IQR increase in ozone was also associated with a 0.24 (95%CI: 0.05-0.42) decrease in pH of EBC reflecting increased airway inflammation. No significant association observed between air pollution and 8-isoprostane in EBC in COPD patients. Our results suggested that short-term exposure to traffic-related air pollution was responsible for exacerbation of airway oxidative stress and inflammation in COPD patients.

  19. Treatments for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP): an overview of systematic reviews

    NARCIS (Netherlands)

    Oaklander, Anne Louise; Lunn, Michael Pt; Hughes, Richard Ac; van Schaik, Ivo N.; Frost, Chris; Chalk, Colin H.

    2017-01-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a chronic progressive or relapsing and remitting disease that usually causes weakness and sensory loss. The symptoms are due to autoimmune inflammation of peripheral nerves. CIPD affects about 2 to 3 per 100,000 of the population.

  20. Evaluating the Oxidative Stress in Inflammation: Role of Melatonin

    Directory of Open Access Journals (Sweden)

    Aroha Sánchez

    2015-07-01

    Full Text Available Oxygen is used by eukaryotic cells for metabolic transformations and energy production in mitochondria. Under physiological conditions, there is a constant endogenous production of intermediates of reactive oxygen (ROI and nitrogen species (RNI that interact as signaling molecules in physiological mechanisms. When these species are not eliminated by antioxidants or are produced in excess, oxidative stress arises. Oxidative stress can damage proteins, lipids, DNA, and organelles. It is a process directly linked to inflammation; in fact, inflammatory cells secrete a large number of cytokines and chemokines responsible for the production of ROI and RNI in phagocytic and nonphagocytic cells through the activation of protein kinases signaling. Currently, there is a wide variety of diseases capable of producing inflammatory manifestations. While, in the short term, most of these diseases are not fatal they have a major impact on life quality. Since there is a direct relationship between chronic inflammation and many emerging disorders like cancer, oral diseases, kidney diseases, fibromyalgia, gastrointestinal chronic diseases or rheumatics diseases, the aim of this review is to describe the use and role of melatonin, a hormone secreted by the pineal gland, that works directly and indirectly as a free radical scavenger, like a potent antioxidant.

  1. Elevated circulating PAI-1 levels are related to lung function decline, systemic inflammation, and small airway obstruction in chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    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

  2. Bile acid metabolism and signaling in cholestasis, inflammation and cancer

    Science.gov (United States)

    Apte, Udayan

    2015-01-01

    Bile acids are synthesized from cholesterol in the liver. Some cytochrome P450 (CYP) enzymes play key roles in bile acid synthesis. Bile acids are physiological detergent molecules, so are highly cytotoxic. They undergo enterohepatic circulation and play important roles in generating bile flow and facilitating biliary secretion of endogenous metabolites and xenobiotics and intestinal absorption of dietary fats and lipid soluble vitamins. Bile acid synthesis, transport and pool size are therefore tightly regulated under physiological conditions. In cholestasis, impaired bile flow leads to accumulation of bile acids in the liver, causing hepatocyte and biliary injury and inflammation. Chronic cholestasis is associated with fibrosis, cirrhosis and eventually liver failure. Chronic cholestasis also increases the risk of developing hepatocellular or cholangiocellular carcinomas. Extensive research in the last two decades has shown that bile acids act as signaling molecules that regulate various cellular processes. The bile acid-activated nuclear receptors are ligand-activated transcriptional factors that play critical roles in the regulation of bile acid, drug and xenobiotic metabolism. In cholestasis, these bile acid-activated receptors regulate a network of genes involved in bile acid synthesis, conjugation, transport and metabolism to alleviate bile acid-induced inflammation and injury. Additionally, bile acids are known to regulate cell growth and proliferation, and altered bile acid levels in diseased conditions have been implicated in liver injury/regeneration and tumorigenesis. We will cover the mechanisms that regulate bile acid homeostasis and detoxification during cholestasis, and the roles of bile acids in the initiation and regulation of hepatic inflammation, regeneration and carcinogenesis. PMID:26233910

  3. Low-Grade Inflammation and Spinal Cord Injury: Exercise as Therapy?

    Directory of Open Access Journals (Sweden)

    Eduardo da Silva Alves

    2013-01-01

    Full Text Available An increase in the prevalence of obesity in people with spinal cord injury can contribute to low-grade chronic inflammation and increase the risk of infection in this population. A decrease in sympathetic activity contributes to immunosuppression due to the lower activation of immune cells in the blood. The effects of physical exercise on inflammatory parameters in individuals with spinal cord injury have not been well described. We conducted a review of the literature published from 1974 to 2012. This review explored the relationships between low-grade inflammation, spinal cord injury, and exercise to discuss a novel mechanism that might explain the beneficial effects of exercise involving an increase in catecholamines and cytokines in people with spinal cord injury.

  4. Low-Grade Inflammation and Spinal Cord Injury: Exercise as Therapy?

    Science.gov (United States)

    da Silva Alves, Eduardo; de Aquino Lemos, Valdir; Ruiz da Silva, Francieli; Lira, Fabio Santos; dos Santos, Ronaldo Vagner Thomathieli; Rosa, João Paulo Pereira; Caperuto, Erico; Tufik, Sergio; de Mello, Marco Tulio

    2013-01-01

    An increase in the prevalence of obesity in people with spinal cord injury can contribute to low-grade chronic inflammation and increase the risk of infection in this population. A decrease in sympathetic activity contributes to immunosuppression due to the lower activation of immune cells in the blood. The effects of physical exercise on inflammatory parameters in individuals with spinal cord injury have not been well described. We conducted a review of the literature published from 1974 to 2012. This review explored the relationships between low-grade inflammation, spinal cord injury, and exercise to discuss a novel mechanism that might explain the beneficial effects of exercise involving an increase in catecholamines and cytokines in people with spinal cord injury. PMID:23533315

  5. Postprandial response of ghrelin and PYY and indices of low-grade chronic inflammation in lean young women with polycystic ovary syndrome.

    Science.gov (United States)

    Zwirska-Korczala, K; Sodowski, K; Konturek, S J; Kuka, D; Kukla, M; Brzozowski, T; Cnota, W; Woźniak-Grygiel, E; Jaworek, J; Bułdak, R; Rybus-Kalinowska, B; Fryczowski, M

    2008-08-01

    The aim of the study were to answer the question 1.) Whether circulating pro-inflammatory markers of endothelial dysfunction and due to chronic low-grade inflammation of obesity, are altered in untreated lean, young relatively healthy polycystic ovary syndrome (PCOS) patients in comparison with healthy controls; 2.) Whether postprandial plasma concentration pattern of ghrelin and PYY can be predictable as risk factors for atherosclerosis and depend of obesity. Forty young women with PCOS were divided in two groups: 19 lean and 21 obese. The control group included 20 lean, healthy volunteers. Plasma total and active ghrelin, total PYY and PYY(3-36), serum adiponectin and insulin were measured using RIA technique, serum sCD40L, visfatin, sP-, sE-selectins, resistin by EIA. Composition of test meal was: 527 kcal total and consisted of 24.1% fat, 54.4% carbohydrate and 21.5% protein. Total and active ghrelin and total PYY were significantly lower in obese PCOS women, whereas active ghrelin was also significantly lower in lean PCOS women compared to controls. Postprandial plasma total ghrelin levels decrease were blunted in lean and obese compared to controls (12.8 % and 18.2% vs 28.2 %). Postprandial plasma active ghrelin decreased in lean and obese PCOS groups (49.9 % and 44.1 %) and controls (63.8 %). PCOS subjects exhibited smaller rises in postprandial levels of total PYY. Postprandial plasma PYY(3-36) levels increased in obese PCOS women (30.9 %) and controls (41%), whereas lean PCOS women exhibited blunted increase (11.5%). sCD40L levels increased, whereas adiponectin decreased in PCOS groups independently, whereas rise in visfatin, sE- and sP-selectin and the fall in adiponectin was associated with obesity. sP- and sE -selectins correlated positively with obesity. In summary, our study provides the first evidence that lean untreated young PCOS women contribute to the so called "pancreatic islet adaptation to insulin resistance" because of ghrelin and PYY

  6. Oral health in patients with chronic kidney disease - emphasis on periodontitis

    OpenAIRE

    Nylund, Karita

    2017-01-01

    ORAL HEALTH IN PATIENTS WITH CHRONIC KIDNEY DISEASE - EMPHASIS ON PERIODONTITIS Background: Periodontitis is a common bacteria-induced chronic inflammatory disease with mild symptoms. It leads to destruction of the periodontium and finally to tooth loss in a susceptible patient. Periodontitis is associated with many systemic diseases such as diabetes, atherosclerosis, cardiovascular diseases, and chronic kidney disease (CKD) through low-grade systemic inflammation. However, no causality c...

  7. Chemical chaperones reduce ER stress and adipose tissue inflammation in high fat diet-induced mouse model of obesity.

    Science.gov (United States)

    Chen, Yaqin; Wu, Zhihong; Zhao, Shuiping; Xiang, Rong

    2016-06-08

    Obesity, which is characteristic by chronic inflammation, is defined as abnormal or excessive fat accumulation in adipose tissues. Endoplasmic reticulum (ER) stress is increased in adipose tissue of obese state and is known to be strongly associated with chronic inflammation. The aim of this study was to investigate the effect of ER stress on adipokine secretion in obese mice and explore the potential mechanisms. In this study, we found high-fat diet induced-obesity contributed to strengthened ER stress and triggered chronic inflammation in adipose tissue. Chemical chaperones, 4-PBA and TUDCA, modified metabolic disorders and decreased the levels of inflammatory cytokines in obese mice fed a high-fat diet. The alleviation of ER stress is in accordance with the decrease of free cholesterol in adipose tissue. Furthermore chemical chaperones suppress NF-κB activity in adipose tissue of obese mice in vivo. In vitro studies showed IKK/NF-κB may be involved in the signal transduction of adipokine secretion dysfunction induced by ER stress. The present study revealed the possibility that inhibition of ER stress may be a novel drug target for metabolic abnormalities associated with obesity. Further studies are now needed to characterize the initial incentive of sustained ER stress in obese.

  8. Radiographic features of esophageal involvement in chronic graft-vs.-host disease

    International Nuclear Information System (INIS)

    McDonald, G.B.; Sullivan, K.M.; Plumley, T.F.

    1984-01-01

    Chronic graft-vs.-host disease (GVHD) is an important late complication of allogeneic bone-marrow transplantation. It resembles several naturally occurring autoimmune diseases and involves the skin, mouth, eyes, liver, and esophagus. The radiographic findings of 14 symptomatic patients with chronic GVHD involving the esophagus were reviewed and found to include webs, ringlike narrowings, and tapering strictures in the mid and upper esophagus. Esophagoscopy revealed characteristic desquamation in the 13 patients studied, but barium studies detected this lesion in only one patient. Knowledge of the site and characteristics of esophageal involvement with chronic GVHD assists the radiologic evaluation of this disorder

  9. Fatty Acids and NLRP3 Inflammasome-Mediated Inflammation in Metabolic Tissues.

    Science.gov (United States)

    Ralston, Jessica C; Lyons, Claire L; Kennedy, Elaine B; Kirwan, Anna M; Roche, Helen M

    2017-08-21

    Worldwide obesity rates have reached epidemic proportions and significantly contribute to the growing prevalence of metabolic diseases. Chronic low-grade inflammation, a hallmark of obesity, involves immune cell infiltration into expanding adipose tissue. In turn, obesity-associated inflammation can lead to complications in other metabolic tissues (e.g., liver, skeletal muscle, pancreas) through lipotoxicity and inflammatory signaling networks. Importantly, although numerous signaling pathways are known to integrate metabolic and inflammatory processes, the nucleotide-binding and oligomerization domain-like receptor, leucine-rich repeat and pyrin domain-containing 3 (NLRP3) inflammasome is now noted to be a key regulator of metabolic inflammation. The NLRP3 inflammasome can be influenced by various metabolites, including fatty acids. Specifically, although saturated fatty acids may promote NLRP3 inflammasome activation, monounsaturated fatty acids and polyunsaturated fatty acids have recently been shown to impede NLRP3 activity. Therefore, the NLRP3 inflammasome and associated metabolic inflammation have key roles in the relationships among fatty acids, metabolites, and metabolic disease. This review focuses on the ability of fatty acids to influence inflammation and the NLRP3 inflammasome across numerous metabolic tissues in the body. In addition, we explore some perspectives for the future, wherein recent work in the immunology field clearly demonstrates that metabolic reprogramming defines immune cell functionality. Although there is a paucity of information about how diet and fatty acids modulate this process, it is possible that this will open up a new avenue of research relating to nutrient-sensitive metabolic inflammation.

  10. Alcohol modulates circulating levels of interleukin-6 and monocyte chemoattractant protein-1 in chronic pancreatitis

    DEFF Research Database (Denmark)

    Pedersen, N; Larsen, S; Seidelin, J B

    2004-01-01

    Cytokines are markers of acute pancreatic inflammation and essential for distant organ injury, but they also stimulate pancreatic fibrogenesis and are thus involved in the progression from acute pancreatitis to chronic pancreatic injury and fibrosis. The aim of this study was to evaluate the circ...... the circulating levels of IL-6, MCP-1, TGF-beta1, IGF-1 and IGFBP-3 in patients with alcoholic chronic pancreatitis (CP).......Cytokines are markers of acute pancreatic inflammation and essential for distant organ injury, but they also stimulate pancreatic fibrogenesis and are thus involved in the progression from acute pancreatitis to chronic pancreatic injury and fibrosis. The aim of this study was to evaluate...

  11. Inflammation arising from obesity reduces taste bud abundance and inhibits renewal.

    Science.gov (United States)

    Kaufman, Andrew; Choo, Ezen; Koh, Anna; Dando, Robin

    2018-03-01

    Despite evidence that the ability to taste is weakened by obesity and can be rescued with weight loss intervention, few studies have investigated the molecular effects of obesity on the taste system. Taste bud cells undergo continual turnover even in adulthood, exhibiting an average life span of only a few weeks, tightly controlled by a balance of proliferation and cell death. Recent data reveal that an acute inflammation event can alter this balance. We demonstrate that chronic low-grade inflammation brought on by obesity reduces the number of taste buds in gustatory tissues of mice-and is likely the cause of taste dysfunction seen in obese populations-by upsetting this balance of renewal and cell death.

  12. microRNAs as a New Mechanism Regulating Adipose Tissue Inflammation in Obesity and as a Novel Therapeutic Strategy in the Metabolic Syndrome

    OpenAIRE

    Ge, Qian; Brichard, Sonia; Yi, Xu; Li, QiFu

    2014-01-01

    Obesity is associated closely with the metabolic syndrome (MS). It is well known that obesity-induced chronic inflammation plays a fundamental role in the pathogenesis of MS. White adipose tissue (AT) is the primary site for the initiation and exacerbation of obesity-associated inflammation. Exploring the mechanisms of white AT inflammation and resetting the immunological balance in white AT could be crucial for the management of MS. Several prominent molecular mechanisms have been proposed t...

  13. Stress induces endotoxemia and low-grade inflammation by increasing barrier permeability

    Directory of Open Access Journals (Sweden)

    Karin ede Punder

    2015-05-01

    Full Text Available Chronic non-communicable diseases (NCDs are the leading causes of work absence, disability and mortality worldwide. Most of these diseases are associated with low-grade inflammation. Here we hypothesize that stresses (defined as homeostatic disturbances can induce low-grade inflammation by increasing the availability of water, sodium and energy-rich substances to meet the increased metabolic demand induced by the stressor. One way of triggering low-grade inflammation is by increasing intestinal barrier permeability through activation of various components of the stress system. Although beneficial to meet the demands necessary during stress, increased intestinal barrier permeability also raises the possibility of the translocation of bacteria and their toxins across the intestinal lumen into the blood circulation. In combination with modern life-style factors, the increase in bacteria/bacterial toxin translocation arising from a more permeable intestinal wall causes a low-grade inflammatory state. We support this hypothesis with numerous studies finding associations with NCDs and markers of endotoxemia, suggesting that this process plays a pivotal and perhaps even a causal role in the development of low-grade inflammation and its related diseases.

  14. Distinguishing multiple rice body formation in chronic subacromial-subdeltoid bursitis from synovial chondromatosis

    International Nuclear Information System (INIS)

    Chen, Albert; Wong, Lun-Yick; Sheu, Chin-Yin; Chen, Be-Fong

    2002-01-01

    Multiple rice body formation is a complication of chronic bursitis. Although it resembles synovial chondromatosis clinically and on imaging, the literature suggests that analysis of radiographic and MR appearances should allow discrimination. We report the imaging findings in a 41-year-old man presenting with rice body formation in chronic subacromial-subdeltoid bursitis. We found that the signal intensity of the rice bodies is helpful in making the diagnosis. (orig.)

  15. Distinguishing multiple rice body formation in chronic subacromial-subdeltoid bursitis from synovial chondromatosis

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Albert; Wong, Lun-Yick; Sheu, Chin-Yin [Department of Radiology, Mackay Memorial Hospital, Taipei (Taiwan); Chen, Be-Fong [Department of Pathology, Mackay Memorial Hospital, Taipei (Taiwan)

    2002-02-01

    Multiple rice body formation is a complication of chronic bursitis. Although it resembles synovial chondromatosis clinically and on imaging, the literature suggests that analysis of radiographic and MR appearances should allow discrimination. We report the imaging findings in a 41-year-old man presenting with rice body formation in chronic subacromial-subdeltoid bursitis. We found that the signal intensity of the rice bodies is helpful in making the diagnosis. (orig.)

  16. 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

    ) 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...

  17. DNA repair is indispensable for survival after acute inflammation

    Science.gov (United States)

    Calvo, Jennifer A.; Meira, Lisiane B.; Lee, Chun-Yue I.; Moroski-Erkul, Catherine A.; Abolhassani, Nona; Taghizadeh, Koli; Eichinger, Lindsey W.; Muthupalani, Sureshkumar; Nordstrand, Line M.; Klungland, Arne; Samson, Leona D.

    2012-01-01

    More than 15% of cancer deaths worldwide are associated with underlying infections or inflammatory conditions, therefore understanding how inflammation contributes to cancer etiology is important for both cancer prevention and treatment. Inflamed tissues are known to harbor elevated etheno-base (ε-base) DNA lesions induced by the lipid peroxidation that is stimulated by reactive oxygen and nitrogen species (RONS) released from activated neutrophils and macrophages. Inflammation contributes to carcinogenesis in part via RONS-induced cytotoxic and mutagenic DNA lesions, including ε-base lesions. The mouse alkyl adenine DNA glycosylase (AAG, also known as MPG) recognizes such base lesions, thus protecting against inflammation-associated colon cancer. Two other DNA repair enzymes are known to repair ε-base lesions, namely ALKBH2 and ALKBH3; thus, we sought to determine whether these DNA dioxygenase enzymes could protect against chronic inflammation-mediated colon carcinogenesis. Using established chemically induced colitis and colon cancer models in mice, we show here that ALKBH2 and ALKBH3 provide cancer protection similar to that of the DNA glycosylase AAG. Moreover, Alkbh2 and Alkbh3 each display apparent epistasis with Aag. Surprisingly, deficiency in all 3 DNA repair enzymes confers a massively synergistic phenotype, such that animals lacking all 3 DNA repair enzymes cannot survive even a single bout of chemically induced colitis. PMID:22684101

  18. Immunotoxicity and environment: immunodysregulation and systemic inflammation in children.

    Science.gov (United States)

    Calderón-Garcidueñas, Lilian; Macías-Parra, Mercedes; Hoffmann, Hans J; Valencia-Salazar, Gildardo; Henríquez-Roldán, Carlos; Osnaya, Norma; Monte, Ofelia Camacho-Del; Barragán-Mejía, Gerardo; Villarreal-Calderon, Rodolfo; Romero, Lina; Granada-Macías, Margarita; Torres-Jardón, Ricardo; Medina-Cortina, Humberto; Maronpot, Robert R

    2009-02-01

    Environmental pollutants, chemicals, and drugs have an impact on children's immune system development. Mexico City (MC) children exposed to significant concentrations of air pollutants exhibit chronic respiratory inflammation, systemic inflammation, neuroinflammation, and cognitive deficits. We tested the hypothesis that exposure to severe air pollution plays a role in the immune responses of asymptomatic, apparently healthy children. Blood measurements for markers of immune function, inflammatory mediators, and molecules interacting with the lipopolysaccharide recognition complex were obtained from two cohorts of matched children (aged 9.7 +/- 1.2 years) from southwest Mexico City (SWMC) (n = 66) and from a control city (n = 93) with criteria pollutant levels below current standards. MC children exhibited significant decreases in the numbers of natural killer cells (p = .003) and increased numbers of mCD14+ monocytes (p < .001) and CD8+ cells (p = .02). Lower concentrations of interferon gamma (p = .009) and granulocyte-macrophage colony-stimulating factor (p < .001), an endotoxin tolerance-like state, systemic inflammation, and an anti-inflammatory response were also present in the highly exposed children. C-reactive protein and the prostaglandin E metabolite levels were positively correlated with twenty-four- and forty-eight-hour cumulative concentrations of PM(2.5). Exposure to urban air pollution is associated with immunodysregulation and systemic inflammation in children and is a major health threat.

  19. Chronic idiopathic intestinal pseudo-obstruction in an English bulldog.

    Science.gov (United States)

    Dvir, E; Leisewitz, A L; Van der Lugt, J J

    2001-05-01

    A case of chronic idiopathic intestinal pseudo-obstruction in an English bulldog is described. The dog was presented with chronic weight loss and vomiting. An intestinal obstruction was suspected based on clinical and radiological findings. A diagnosis of chronic idiopathic intestinal pseudo-obstruction was made on the basis of full thickness intestinal biopsies. The dog was refractory to any antiemetic therapy. Necropsy revealed marked atrophy and fibrosis of the tunica muscularis, together with a mononuclear cell infiltrate extending from the duodenum to the colon. This case was presented with clinical findings consistent with visceral myopathy in humans--namely, atony and dilatation of the whole gut--but the histological findings resembled sclerosis limited to the gastrointestinal tract.

  20. Intake of traditional Inuit diet vary in parallel with inflammation as estimated from YKL-40 and hsCRP in Inuit and non-Inuit in Greenland

    DEFF Research Database (Denmark)

    Schæbel, Louise Holm; Vestergaard, H; Laurberg, Peter Marvin

    2013-01-01

    Chronic low-grade inflammation is involved in the initiation and progression of atherosclerosis and ischemic heart disease. This was rare in pre-western Inuit who lived on a diet that consisted mainly of marine mammals rich in n-3 fatty acids.......Chronic low-grade inflammation is involved in the initiation and progression of atherosclerosis and ischemic heart disease. This was rare in pre-western Inuit who lived on a diet that consisted mainly of marine mammals rich in n-3 fatty acids....