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Sample records for proven chronic inflammatory

  1. Chronic inflammatory demyelinating polyneuropathy.

    PubMed

    Mathey, Emily K; Pollard, John D

    2013-10-15

    Chronic inflammatory demyelinating polyneuropathy (CIDP) is the commonest treatable neuropathy in the western world. Untreated it may result in severe disability but if diagnosed and treated early there is effective treatment for the majority of patients. Typical CIDP is readily recognised but the diagnosis of other subgroups can be more challenging. The pathology of polyradiculoneuropathies such as CIDP characteristically affects the most proximal regions of the peripheral nervous system, nerve roots and major plexuses. It is important to test these regions with electrodiagnostic studies since routine neurophysiology may not encounter regions of pathology. Although accepted as an autoimmune disorder with an underlying immunopathology involving T cell and B cell responses, there is no agreement on major target antigens; however recent studies have highlighted a role for molecules in non compact myelin which play an essential role in the formation and maintenance of the nodal structures and hence in the function of ion channels central to saltatory conduction. Controlled trials have proven the efficacy of corticosteroid, intravenous immunoglobulin and plasma exchange in the short term and intravenous immunoglobulin also in the long term. Immunosuppressive agents are widely used but their efficacy has not been proven in controlled trials. Recent trials have shown the importance of attempting treatment withdrawal in patients apparently in remission to conserve treatments that are very expensive and in short supply, since a significant proportion of patients may enter long lasting remission following short term therapy. For the relatively small group of patients who do not respond to these first line therapies new agents including monoclonal antibodies may have a role. PMID:23146613

  2. Chronic Inflammatory Demyelinating Polyneuropathy

    PubMed Central

    Dimachkie, Mazen M.; Barohn, Richard J.

    2014-01-01

    Opinion statement Chronic Inflammatory polyneuropathies are an important group of neuromuscular disorders that present chronically and progress over more than 8 weeks, being referred to as chronic inflammatory demyelinating polyneuropathy (CIDP). Despite tremendous progress in elucidating disease pathogenesis, the exact triggering event remains unknown. Our knowledge regarding diagnosis and management of CIDP and its variants continues to expand, resulting in improved opportunities for identification and treatment. Most clinical neurologists will be involved in the management of patients with these disorders, and should be familiar with available therapies for CIDP. We review the distinctive clinical, laboratory, and electro-diagnostic features that aid in diagnosis. We emphasize the importance of clinical patterns that define treatment responsiveness and the most appropriate therapies in order to improve prognosis. PMID:23564314

  3. Chronic inflammatory systemic diseases

    PubMed Central

    Straub, Rainer H.; Schradin, Carsten

    2016-01-01

    It has been recognized that during chronic inflammatory systemic diseases (CIDs) maladaptations of the immune, nervous, endocrine and reproductive system occur. Maladaptation leads to disease sequelae in CIDs. The ultimate reason of disease sequelae in CIDs remained unclear because clinicians do not consider bodily energy trade-offs and evolutionary medicine. We review the evolution of physiological supersystems, fitness consequences of genes involved in CIDs during different life-history stages, environmental factors of CIDs, energy trade-offs during inflammatory episodes and the non-specificity of CIDs. Incorporating bodily energy regulation into evolutionary medicine builds a framework to better understand pathophysiology of CIDs by considering that genes and networks used are positively selected if they serve acute, highly energy-consuming inflammation. It is predicted that genes that protect energy stores are positively selected (as immune memory). This could explain why energy-demanding inflammatory episodes like infectious diseases must be terminated within 3–8 weeks to be adaptive, and otherwise become maladaptive. Considering energy regulation as an evolved adaptive trait explains why many known sequelae of different CIDs must be uniform. These are, e.g. sickness behavior/fatigue/depressive symptoms, sleep disturbance, anorexia, malnutrition, muscle wasting—cachexia, cachectic obesity, insulin resistance with hyperinsulinemia, dyslipidemia, alterations of steroid hormone axes, disturbances of the hypothalamic-pituitary-gonadal (HPG) axis, hypertension, bone loss and hypercoagulability. Considering evolved energy trade-offs helps us to understand how an energy imbalance can lead to the disease sequelae of CIDs. In the future, clinicians must translate this knowledge into early diagnosis and symptomatic treatment in CIDs. PMID:26817483

  4. Canine chronic inflammatory rhinitis.

    PubMed

    Windsor, Rebecca C; Johnson, Lynelle R

    2006-05-01

    Chronic inflammatory rhinitis is commonly found in dogs with chronic nasal disease and is characterized by lymphoplasmacytic infiltrates in the nasal mucosa in the absence of an obvious etiologic process. The pathogenesis of lymphoplasmacytic rhinitis remains unknown. Animals respond poorly to antibiotics, oral glucocorticoids, and antihistamines, making primary infectious, immune-mediated, or allergic etiologies unlikely. Aberrant immune response to inhaled organisms or allergens may induce inflammation in some animals. Common clinical signs include nasal discharge, sneezing, coughing, epistaxis, and stertor. Diagnosis is made by performing a thorough history, physical examination, radiography or advanced imaging (via computed tomography or magnetic resonance imaging), rhinoscopy, and nasal mucosal biopsy to rule out primary etiologies of nasal discharge. Treatment strategies have included various antibiotics, antihistamines, oral and inhalant steroids, nonsteroidal antiinflammatories, and antifungal medications. Some dogs may respond partially to doxycycline or azithromycin, although it is unclear whether response is related to antimicrobial or antiinflammatory properties of these drugs. Hydration of the nasal cavity through nasal drops or aerosols may limit nasal discharge, and some animals may improve with inhalant (but rarely oral) glucocorticoids. PMID:16711613

  5. [Biomarkers for chronic inflammatory diseases].

    PubMed

    Holzinger, D; Föll, D

    2015-12-01

    Inflammatory disorders of childhood, such as juvenile idiopathic arthritis (JIA) and inflammatory bowel disease (IBD) are a challenge for laboratory diagnostics. Firstly, the classical inflammatory markers, such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) often inadequately reflect disease activity but on the other hand there are few specific biomarkers that can be helpful in managing these diseases. Acute phase proteins reflect the systemic inflammatory response insufficiently as their increase is only the indirect result of local inflammatory processes. Modern inflammation diagnostics aim to reflect these local processes and to allow precise monitoring of disease activity. Experimental biomarkers, such as S100 proteins can detect subclinical inflammatory activity. In addition, established laboratory parameters exist for JIA [antinuclear antibodies (ANA), rheumatoid factor (RF), antibodies against cyclic citrullinated peptide (anti-CCP)] and for chronic IBD (fecal calprotectin) that are useful in the treatment of these diseases. PMID:26608264

  6. Chronic inflammatory polyneuropathy

    MedlinePlus

    ... nerves outside the brain or spinal cord ( peripheral neuropathy ). Polyneuropathy means several nerves are involved. It usually ... demyelinating polyneuropathy (CIDP) is the most common chronic neuropathy caused by an abnormal immune response. CIDP occurs ...

  7. Hypertrophic osteoarthropathy of chronic inflammatory bowel disease

    SciTech Connect

    Oppenheimer, D.A.; Jones, H.H.

    1982-12-01

    The case of a 14-year old girl with painful periostitis and ulcerative colitis is reported. The association of chronic inflammatory bowel disease with osteoarthropathy is rare and has previously been reported in eight patients. The periosteal reaction found in association with inflammatory bowel disease is apparently related to a chronic disease course and may cause extreme localized pain.

  8. Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

    MedlinePlus

    ... and legs, loss of deep tendon reflexes (areflexia), fatigue, and abnormal sensations. CIDP is closely related to Guillain-Barre syndrome and it is considered the chronic counterpart of that acute disease. Is there any ...

  9. Endothelial Dysfunction in Chronic Inflammatory Diseases

    PubMed Central

    Steyers, Curtis M.; Miller, Francis J.

    2014-01-01

    Chronic inflammatory diseases are associated with accelerated atherosclerosis and increased risk of cardiovascular diseases (CVD). As the pathogenesis of atherosclerosis is increasingly recognized as an inflammatory process, similarities between atherosclerosis and systemic inflammatory diseases such as rheumatoid arthritis, inflammatory bowel diseases, lupus, psoriasis, spondyloarthritis and others have become a topic of interest. Endothelial dysfunction represents a key step in the initiation and maintenance of atherosclerosis and may serve as a marker for future risk of cardiovascular events. Patients with chronic inflammatory diseases manifest endothelial dysfunction, often early in the course of the disease. Therefore, mechanisms linking systemic inflammatory diseases and atherosclerosis may be best understood at the level of the endothelium. Multiple factors, including circulating inflammatory cytokines, TNF-α (tumor necrosis factor-α), reactive oxygen species, oxidized LDL (low density lipoprotein), autoantibodies and traditional risk factors directly and indirectly activate endothelial cells, leading to impaired vascular relaxation, increased leukocyte adhesion, increased endothelial permeability and generation of a pro-thrombotic state. Pharmacologic agents directed against TNF-α-mediated inflammation may decrease the risk of endothelial dysfunction and cardiovascular disease in these patients. Understanding the precise mechanisms driving endothelial dysfunction in patients with systemic inflammatory diseases may help elucidate the pathogenesis of atherosclerosis in the general population. PMID:24968272

  10. Mucin overproduction in chronic inflammatory lung disease

    PubMed Central

    Hauber, Hans-Peter; Foley, Susan C; Hamid, Qutayba

    2006-01-01

    Mucus overproduction and hypersecretion are commonly observed in chronic inflammatory lung disease. Mucins are gel-forming glycoproteins that can be stimulated by a variety of mediators. The present review addresses the mechanisms involved in the upregulation of secreted mucins. Mucin induction by neutrophil elastase, bacteria, cytokines, growth factors, smoke and cystic fibrosis transmembrane conductance regulator malfunction are also discussed. PMID:16983448

  11. Chronic Inflammatory Gingival Overgrowths: Laser Gingivectomy & Gingivoplasty

    PubMed Central

    Shankar, B Shiva; T, Ramadevi; S, Neetha M; Reddy, P Sunil Kumar; Saritha, G; Reddy, J Muralinath

    2013-01-01

    It is quite common to note chronic inflammatory Gingival overgrowths during and/or post orthodontic treatment. Sometimes the overgrowths may even potentially complicate and/or interrupt orthodontic treatment. With the introduction of soft tissue lasers these problems can now be addressed more easily. Amongst many LASERS now available in Dentistry DIODE LASERS seem to be most ideal for orthodontic soft tissue applications. As newer treatments herald into minimally invasive techniques, DIODE LASERS are becoming more promising both in patient satisfaction and dentist satisfaction. How to cite this article: Shankar BS, Ramadevi T, Neetha M S, Reddy P S K, Saritha G, Reddy J M. Chronic Inflammatory Gingival Overgrowths: Laser Gingivectomy & Gingivoplasty. J Int Oral Health 2013; 5(1):83-87. PMID:24155582

  12. Chronic Inflammatory Diseases and Endothelial Dysfunction

    PubMed Central

    Castellon, Xavier; Bogdanova, Vera

    2016-01-01

    Chronic inflammatory diseases are associated with increases in cardiovascular diseases (CVD) and subclinical atherosclerosis as well as early-stage endothelial dysfunction screening using the FMD method (Flow Mediated Dilation). This phenomenon, referred to as accelerated pathological remodeling of arterial wall, could be attributed to traditional risk factors associated with atherosclerosis. Several new non-invasive techniques have been used to study arterial wall’s structural and functional alterations. These techniques (based of Radio Frequency, RF) allow for an assessment of artery age through calculations of intima-media thickness (RF- QIMT), pulse wave rate (RF- QAS) and endothelial dysfunction degree (FMD). The inflammatory and autoimmune diseases should now be considered as new cardiovascular risk factors, result of the major consequences of oxidative stress and RAS (Renin Angiotensin System) imbalance associated with the deleterious effect of known risk factors that lead to the alteration of the arterial wall. Inflammation plays a key role in all stages of the formation of vascular lesions maintained and exacerbated by the risk factors. The consequence of chronic inflammation is endothelial dysfunction that sets in and we can define it as an integrated marker of the damage to arterial walls by classic risk factors. The atherosclerosis, which develops among these patients, is the main cause for cardiovascular morbi-mortality and uncontrolled chronic biological inflammation, which quickly favors endothelial dysfunction. These inflammatory and autoimmune diseases should now be considered as new cardiovascular risk factors. PMID:26815098

  13. Chronic progressive external ophthalmoplegia with inflammatory myopathy.

    PubMed

    Chen, Ting; Pu, Chuanqiang; Shi, Qiang; Wang, Qian; Cong, Lu; Liu, Jiexiao; Luo, Hongyu; Fei, Lingna; Tang, Wei; Yu, Shanshan

    2014-01-01

    Chronic progressive external ophthalmoplegia is one of mitochondrial disorders, characterized by ptosis, limitation of eye movement, variably severe bulbar muscle weakness and proximal limb weakness. Chronic progressive external ophthalmoplegia complicated with acquired disease is extremely rare. We report a 44 years old male patient with more than 20 years of chronic progressive bilateral ptosis and limitation of eye movements manifested dysarthria, dysphagia and neck muscle weakness for 3 years. The first muscle biopsy showed red-ragged fibers and cytochrome c oxidase negative fibers as well as inflammatory cells infiltration. Electron microscopy revealed paracrystalline inclusions. Mitochondrial genetic analysis demonstrated a large-scale mtDNA deletion of m.8470_13446del4977. The patient was treated with prednisone. In a three-year follow-up study, the second biopsy was performed. Before the treatment, except bilateral ptosis and external ophthalmopelgia, this patient presented bulbar muscle weakness and neck muscle weakness. After treated with prednisone, the symptoms of dysphagia, dysarthria and neck muscle weakness were significantly improved, and the second biopsy showed only mitochondrial myopathy pathology but the inflammations disappeared. Here, we report a patient with chronic progressive external ophthalmoplegia complicated with inflammatory myopathy and after treated with prednisone as myositis, he had a significant therapeutic effect. PMID:25674260

  14. [Sweet's syndrome. Its association with chronic inflammatory bowel disease].

    PubMed

    Calvo Catalá, J; González Pérez, J A; Febrer Bosch, I; Oliver Mas, V; Herrera Ballester, A

    1990-07-01

    Sweet's syndrome, or febrile neutrophilic dermatosis, is a disease first described by Sweet R.D. in 1964 as a dermatologic disease. Subsequently, it has been associated to several disease. One of those rarely describe is the association to chronic intestinal inflammatory disease. We reviewed the cases studied in our hospital since 1980 and found two cases associated to chronic intestinal inflammatory disease. We recommend the carrying out of gastrointestinal studies in patients afflicted by Sweet's syndrome to detect its association. PMID:2103250

  15. The potential of food protein-derived anti-inflammatory peptides against various chronic inflammatory diseases.

    PubMed

    Majumder, Kaustav; Mine, Yoshinori; Wu, Jianping

    2016-05-01

    Inflammation is considered as one of the major causes for the initiation of various chronic diseases such as asthma, cancer, cardiovascular disease, diabetes, obesity, inflammatory bowel disease, osteoporosis and neurological diseases like Parkinson's disease. Increasing scientific evidence has delineated that inflammatory markers such as TNF-α, IL-1, IL-6, IL-8 and CRP and different transcription factors such as NF-κB and STAT are the major key factors that regulate these inflammatory diseases. Food protein-derived bioactive peptides have been shown to exhibit anti-inflammatory activity by inhibiting or reducing the expression of these inflammatory biomarkers and/or by modulating the activity of these transcription factors. This review aims to discuss various molecular targets and underlying mechanisms of food protein-derived anti-inflammatory peptides and to explore their potential against various chronic inflammatory diseases. © 2015 Society of Chemical Industry. PMID:26711001

  16. Chronic Inflammatory Demyelinating Polyradiculoneuropathy: From Bench to Bedside

    PubMed Central

    Peltier, Amanda C.; Donofrio, Peter D.

    2015-01-01

    Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) is the most common treatable chronic autoimmune neuropathy. Multiple diagnostic criteria have been established, with the primary goal of identifying neurophysiologic hallmarks of acquired demyelination. Treatment modalities have expanded to include numerous immuno-modulatory therapies, although the best evidence continues to be for corticosteroids, plasma exchange, and intravenous immunoglobulins (IVIg). This review describes the pathology, epidemiology, pathogenesis, diagnosis, and treatment of CIDP. PMID:23117943

  17. Arresting the Inflammatory Drive of Chronic Lymphocytic Leukemia with Ibrutinib.

    PubMed

    Bachireddy, Pavan; Wu, Catherine J

    2016-04-01

    The clinical success of agents targeting the B-cell receptor signaling pathway in chronic lymphocytic leukemia (CLL) may also derive from disrupting the CLL microenvironment. Investigation of the immunomodulatory effects of these agents illuminates the unique immunobiology of CLL and highlights potential targets for dismantling the chronic inflammatory drive.Clin Cancer Res; 22(7); 1547-9. ©2016 AACRSee related article by Niemann et al., p. 1572. PMID:26847060

  18. Chronic Inflammatory Demyelinating Polyneuropathy Following Anti-TNF-α Therapy With Infliximab for Crohn's Disease.

    PubMed

    Kamel, Amir Y; Concepcion, Orestes; Schlachterman, Alexander; Glover, Sarah; Forsmark, Christopher Y

    2016-04-01

    We present a 29-year-old male with Crohn's disease who developed chronic inflammatory demyelinating polyneuropathy (CIDP) related to infliximab therapy. He developed lower extremity weakness and dysesthesia 3 weeks after a fourth infliximab dose. Laboratory examination revealed an elevated cerebrospinal fluid protein without pleocytosis. The patient initially responded to plasmapheresis therapy with marked symptomatic improvement, but relapsed and was refractory to subsequent treatments with plasmaphereisis, intravenous immunoglobulin, and glucocorticoids. While a causal relationship between infliximab and CIDP cannot be proven, clinicians should monitor Crohn's disease patients who are receiving TNF-α antagonists for neurologic symptoms suggestive of demyelinating disease. PMID:27144200

  19. Chronic Inflammatory Demyelinating Polyneuropathy Following Anti-TNF-α Therapy With Infliximab for Crohn's Disease

    PubMed Central

    Concepcion, Orestes; Schlachterman, Alexander; Glover, Sarah; Forsmark, Christopher Y.

    2016-01-01

    We present a 29-year-old male with Crohn's disease who developed chronic inflammatory demyelinating polyneuropathy (CIDP) related to infliximab therapy. He developed lower extremity weakness and dysesthesia 3 weeks after a fourth infliximab dose. Laboratory examination revealed an elevated cerebrospinal fluid protein without pleocytosis. The patient initially responded to plasmapheresis therapy with marked symptomatic improvement, but relapsed and was refractory to subsequent treatments with plasmaphereisis, intravenous immunoglobulin, and glucocorticoids. While a causal relationship between infliximab and CIDP cannot be proven, clinicians should monitor Crohn's disease patients who are receiving TNF-α antagonists for neurologic symptoms suggestive of demyelinating disease. PMID:27144200

  20. Diarrhea in chronic inflammatory bowel diseases.

    PubMed

    Wenzl, Heimo H

    2012-09-01

    Diarrhea is a common clinical feature of inflammatory bowel diseases and may be accompanied by abdominal pain, urgency, and fecal incontinence. The pathophysiology of diarrhea in these diseases is complex, but defective absorption of salt and water by the inflamed bowel is the most important mechanism involved. In addition to inflammation secondary to the disease, diarrhea may arise from a variety of other conditions. It is important to differentiate the pathophysiologic mechanisms involved in the diarrhea in the individual patient to provide the appropriate therapy. This article reviews microscopic colitis, ulcerative colitis, and Crohn's disease, focusing on diarrhea. PMID:22917170

  1. MNGIE neuropathy: five cases mimicking chronic inflammatory demyelinating polyneuropathy.

    PubMed

    Bedlack, Richard S; Vu, Tuan; Hammans, Simon; Sparr, Steven A; Myers, Bennett; Morgenlander, Joel; Hirano, Michio

    2004-03-01

    We report five patients with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) who had demyelinating peripheral neuropathy. The MNGIE neuropathy had clinical and electrodiagnostic features typical of acquired, rather than inherited, etiologies. In fact, three patients were actually treated for chronic inflammatory demyelinating polyneuropathy (CIDP). We discuss findings that may help distinguish patients with MNGIE from those with CIDP. PMID:14981734

  2. INFLAMMATORY ABDOMINAL AORTIC ANEURYSM--A FORM OF CHRONIC PERIAORTITIS.

    PubMed

    Pop, Corina; Nemeş, Roxana Maria; Jantea, Petruţa; Tomescu, Alina; Postolache, Paraschiva

    2015-01-01

    Chronic periaortitis represents a unique pathogenic concept for three entities: Inflammatory Abdominal Aortic Aneurysm, Idiopathic Retroperitoneal Fibrosis and Perianeurysmal Retroperitoneal Fibrosis. The fundamental meaning of an inflammatory reaction to advanced atherosclerosis has been developed on the bottom of clinical and histological features. The triad of abdominal pain, weight loss and elevated inflammatory markers: erythrocyte sedimentation rate/C-reactive protein in patients with abdominal aortic aneurysms revealed on contrast-enhanced computer tomography is highly suggestive for inflammatory aneurysm. We report a case of a heavy-smoker adult male presented with suddenly abdominal symptoms suggestive for mesenteric ischemia which have proved to be due to inflammatory abdominal aortic aneurysm. The most favorable management of patients with inflammatory aneurysm is ambiguous. Surgical approach seems reasonable even supposing inflammatory aneurysm emerges less likely to rupture than the atherosclerotic variant. Corticosteroids are used in inoperable inflammatory aneurysm, even if is well known that this treatment does not change the long-term outcome of the disease. Surgical-open or Endovascular Repair of the aneurysm is the elective treatment. PMID:26793850

  3. Pathophysiology and treatment of inflammatory anorexia in chronic disease.

    PubMed

    Braun, Theodore P; Marks, Daniel L

    2010-12-01

    Decreased appetite and involuntary weight loss are common occurrences in chronic disease and have a negative impact on both quality of life and eventual mortality. Weight loss in chronic disease comes from both fat and lean mass, and is known as cachexia. Both alterations in appetite and body weight loss occur in a wide variety of diseases, including cancer, heart failure, renal failure, chronic obstructive pulmonary disease and HIV. An increase in circulating inflammatory cytokines has been implicated as a uniting pathogenic mechanism of cachexia and associated anorexia. One of the targets of inflammatory mediators is the central nervous system, and in particular feeding centers in the hypothalamus located in the ventral diencephalon. Current research has begun to elucidate the mechanisms by which inflammation reaches the hypothalamus, and the neural substrates underlying inflammatory anorexia. Research into these neural mechanisms has suggested new therapeutic possibilities, which have produced promising results in preclinical and clinical trials. This review will discuss inflammatory signaling in the hypothalamus that mediates anorexia, and the opportunities for therapeutic intervention that these mechanisms present. PMID:21475703

  4. Novel immunotherapeutic strategies in chronic inflammatory demyelinating polyneuropathy.

    PubMed

    Mathis, Stéphane; Vallat, Jean-Michel; Magy, Laurent

    2016-02-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a chronic immune-mediated neuropathy: it is clinically heterogeneous (relapsing-remitting form, chronic progressive form, monophasic form or CIDP having a Guillain-Barré syndrome-like onset), but potentially treatable. Although its pathophysiology remains largely unknown, CIDP is considered an immune-mediated neuropathy. Therefore, many immunotherapies have been proposed in this peripheral nervous system disorder, the most known efficient treatments being intravenous immunoglobulin, corticosteroids and plasma exchange. However, these therapies remain unsatisfactory for many patients, so numerous other immunotherapeutic strategies have been evaluated, based on their immunosuppressant or immunomodulatory potency. We have performed a large review of the literature about treatment in CIDP, with a special emphasis on novel and alternative immunotherapeutic strategies. PMID:26809024

  5. Chronic venous disease - Part I: Inflammatory biomarkers in wound healing.

    PubMed

    Ligi, Daniela; Mosti, Giovanni; Croce, Lidia; Raffetto, Joseph D; Mannello, Ferdinando

    2016-10-01

    Venous leg ulcers (VLUs) produce wound fluid (WF), as a result of inflammatory processes within the wound. It is unclear if WF from different healing phases of VLU has a peculiar biochemical profile and how VLU microenvironment affects the wound healing mechanisms. This study was conducted to evaluate the cytokine/chemokine profiles in WF from distinct VLU phases, in WF- and LPS-stimulated monocytes and treated with glycosaminoglycan Sulodexide, a therapeutic option for VLU healing. WF and plasma were collected from patients with VLU during active inflammatory (Infl) and granulating (Gran) phases. Demographics, clinical characteristics and pain measurements were evaluated. WF, plasma, and THP-1 supernatants were analyzed for 27 inflammatory mediators by multiplex immunoassay. Our results demonstrated that: 1) pain was significantly increased in patients with Infl compared to Gran VLU; 2) cytokine profile of Infl WF was found to be statistically different from that Gran WF, as well significantly increased respect to plasma; 3) LPS- and WF-stimulation of THP-1 cells significantly increased the expression of several cytokines compared to untreated cells; 4) Sulodexide treatment of both LPS- and WF-stimulated THP-1 monocytes was able to significantly down-regulate the release of peculiar inflammatory mediators. Our study highlighted the importance to understand biomolecular processes underlying CVI when providing treatment for chronic VLU. Identification of inflammatory biomarkers in leg ulcer microenvironment, may provide useful tools for predicting healing outcome and developing targeted therapies. PMID:27478145

  6. Chronic Inflammatory Diseases: Progress and Prospect with Herbal Medicine.

    PubMed

    Ghosh, Nilanjan; Ali, Asif; Ghosh, Rituparna; Das, Shaileyee; Mandal, Subhash C; Pal, Mahadeb

    2016-01-01

    Diseases associated with chronic inflammatory pathology claim a major share of worldwide deaths each year. A principal reason behind the huge number of casualties is associated with mild or unnoticed symptoms for long period of time since the outset, and that specific treatment options for these diseases have not yet emerged. Current anti-inflammatory drugs essentially have become ineffective for long term protection from these diseases as they also interfere with essential cellular pathways and associated toxicities. Notably, recent studies with a number of phytochemicals have shown promising results. These compounds isolated from various medicinal plants express their anti-inflammatory activities by down regulating expression of several crucial pro-inflammatory mediators. These are mostly antioxidants; inhibit induction of key transcription factors like nuclear factor kappa B (NF-κB) that are responsible for expression of proinflammatory mediators, and other growth regulators. Definitely, some of these compounds have the potential to be developed into new therapeutic agents to better control inflammation associated diseases in near future. This review summarizes recent findings on the molecular mechanisms through which various inflammatory activities are linked to disease progression and a group of natural products that have shown promise in controlling these processes. PMID:26561064

  7. Challenges in the treatment of chronic inflammatory demyelinating polyradiculoneuropathy.

    PubMed

    Guimarães-Costa, R; Iancu Ferfoglia, R; Viala, K; Léger, J-M

    2014-10-01

    Chronic idiopathic demyelinating polyradiculoneuropathy (CIDP) is a rare disease, the most frequent one within the spectrum of the so-called "chronic immune-mediated neuropathies". Challenges in the treatment of CIDP firstly concern its diagnosis, which may be difficult, mainly for the atypical forms. Secondly, challenges encompass the choice of the first-line treatment, such as corticosteroids, intravenous immunoglobulins (IVIg), and plasma exchanges (PE) that have been proven as efficacious by several randomized controlled trials (RCT). Recent reports have focused on both different regimens of corticosteroids, and the occurrence of relapses following treatment with either corticosteroids or IVIg. These data may be helpful for the choice of the first-line treatment and may result in changing the guidelines for treatment of CIDP in clinical practice. The third and more difficult challenge is to manage long-term treatment for CIDP, since no immunomodulatory treatment has to date been proven as efficacious in this situation. Lastly, challenges in the treatment concern the choice of the best outcome measure for CIDP in RCT and clinical practice. The aim of this article is to overview the results of the more recently reported published trials for CIDP, and to give some insights for the current and future management of CIDP. PMID:25200479

  8. Chronic inflammatory demyelinating polyradiculoneuropathy: from pathology to phenotype

    PubMed Central

    Mathey, Emily K; Park, Susanna B; Hughes, Richard A C; Pollard, John D; Armati, Patricia J; Barnett, Michael H; Taylor, Bruce V; Dyck, P James B; Kiernan, Matthew C; Lin, Cindy S-Y

    2015-01-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an inflammatory neuropathy, classically characterised by a slowly progressive onset and symmetrical, sensorimotor involvement. However, there are many phenotypic variants, suggesting that CIDP may not be a discrete disease entity but rather a spectrum of related conditions. While the abiding theory of CIDP pathogenesis is that cell-mediated and humoral mechanisms act together in an aberrant immune response to cause damage to peripheral nerves, the relative contributions of T cell and autoantibody responses remain largely undefined. In animal models of spontaneous inflammatory neuropathy, T cell responses to defined myelin antigens are responsible. In other human inflammatory neuropathies, there is evidence of antibody responses to Schwann cell, compact myelin or nodal antigens. In this review, the roles of the cellular and humoral immune systems in the pathogenesis of CIDP will be discussed. In time, it is anticipated that delineation of clinical phenotypes and the underlying disease mechanisms might help guide diagnostic and individualised treatment strategies for CIDP. PMID:25677463

  9. Managing Inflammatory Manifestations in Patients with Chronic Granulomatous Disease.

    PubMed

    Magnani, Alessandra; Mahlaoui, Nizar

    2016-10-01

    Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by lack of phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, which results in inflammatory dysregulation and increased susceptibility to infections. Patients with CGD may develop severe obstructive disorders of the digestive tract as a result of their dysregulated inflammatory response. Despite a growing focus on inflammatory manifestations in CGD, the literature data on obstructive complications are far less extensive than those on infectious complications. Diagnosis and management of patients with concomitant predispositions to infections and hyperinflammation are particularly challenging. Although the inflammatory and granulomatous manifestations of CGD usually respond rapidly to steroid treatment, second-line therapies (immunosuppressants and biologics) may be required in refractory cases. Indeed, immunosuppressants (such as anti-tumor necrosis factor agents, thalidomide, and anakinra) have shown some efficacy, but the value of this approach is controversial, given the questionable risk-to-benefit ratio and the small numbers of patients treated to date. Significant progress in allogeneic hematopoietic stem cell transplantation (the only curative treatment for CGD) has been made through better supportive care and implementation of improved, reduced-intensity conditioning regimens. Gene therapy may eventually be an option for patients lacking a suitable donor; clinical trials with new, safer vectors are ongoing at a few centers. PMID:27299584

  10. Accelerated atherosclerosis in patients with chronic inflammatory rheumatologic conditions

    PubMed Central

    Hong, Jison; Maron, David J; Shirai, Tsuyoshi; Weyand, Cornelia M

    2015-01-01

    Atherosclerosis is a complex inflammatory disease involving aberrant immune and tissue healing responses, which begins with endothelial dysfunction and ends with plaque development, instability and rupture. The increased risk for coronary artery disease in patients with rheumatologic diseases highlights how aberrancy in the innate and adaptive immune system may be central to development of both disease states and that atherosclerosis may be on a spectrum of immune-mediated conditions. Recognition of the tight association between chronic inflammatory disease and complications of atherosclerosis will impact the understanding of underlying pathogenic mechanisms and change diagnostic and therapeutic approaches in patients with rheumatologic syndromes as well as patients with coronary artery disease. In this review, we provide a summary of the role of the immune system in atherosclerosis, discuss the proposed mechanisms of accelerated atherosclerosis seen in association with rheumatologic diseases, evaluate the effect of immunosuppression on atherosclerosis and provide updates on available risk assessment tools, biomarkers and imaging modalities. PMID:27042216

  11. Treatment of chronic inflammatory demyelinating polyradiculoneuropathy with methotrexate

    PubMed Central

    Fialho, D; Chan, Y‐C; Allen, D C; Reilly, M M; Hughes, R A C

    2006-01-01

    We discovered many reports of other immunosuppressive drugs being used in adults with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) but none of methotrexate. As weekly low dose oral methotrexate is safe, effective, and well tolerated in other diseases, we treated 10 patients with otherwise treatment resistant CIDP. Seven showed improvement in strength by at least two points on the MRC sum score and three worsened. Only two showed an improvement in disability and both were also receiving corticosteroids. We discuss the difficulty of detecting an improvement in treatment resistant CIDP and propose methotrexate as a suitable agent for testing in a randomised trial. PMID:16543541

  12. Autoantibodies against vinculin in patients with chronic inflammatory demyelinating polyneuropathy.

    PubMed

    Beppu, Minako; Sawai, Setsu; Satoh, Mamoru; Mori, Masahiro; Kazami, Takahiro; Misawa, Sonoko; Shibuya, Kazumoto; Ishibashi, Masumi; Sogawa, Kazuyuki; Kado, Sayaka; Kodera, Yoshio; Nomura, Fumio; Kuwabara, Satoshi

    2015-10-15

    To identify the target molecules of chronic inflammatory demyelinating polyneuropathy (CIDP), we used proteomic-based approach in the extracted proteins from porcine cauda equina. Two of 31 CIDP patients had markedly elevated serum autoantibodies against vinculin, a cell adhesion protein. Both of the patients with anti-vinculin antibodies had similar clinical manifestation, which are compatible with those of "typical" CIDP. Immunocytochemistry showed that vinculin was stained at the myelin sheath of the sciatic nerves by serum samples. Our results suggest that vinculin is a possible immunological target molecule in a subpopulation of typical CIDP patients. PMID:26439954

  13. Sarah's Knee: A Famous Actress With Chronic, Inflammatory Monoarthritis.

    PubMed

    Pinals, Robert S

    2004-02-01

    Sarah Bernhardt had a recurrent and later persistent inflammatory arthritis of her right knee for more than 25 years. She probably had pulmonary tuberculosis, starting a dozen years before the arthritis, and her chronic synovitis may have been tuberculous. Several months in a cast led to deterioration and later amputation of the leg, an outcome that might have been prevented by surgical arthrodesis. Despite the loss of her limb and progressive renal failure, she continued an active theatrical career until her death at age 78. PMID:17043454

  14. Inflammatory Markers and Procoagulants in Chronic Renal Disease Stages 1-4

    PubMed Central

    Muslimovic, Alma; Rasic, Senija; Tulumovic, Denijal; Hasanspahic, Senad; Rebic, Damir

    2015-01-01

    Introduction: Starting from the point that the chronic kidney disease (CKD) is chronic, inflammatory and hypercoagulable state characterized by an increase in procoagulant and inflammatory markers high cardiovascular morbidity and mortality in these patients could be explained. Aim: The aim of the research was to monitor inflammatory markers and procoagulants in various stages of kidney disease (stage 1-4). Materials and Methods: The research included 120 subjects older than 18 years with CKD stages 1-4 examined and monitored in Clinic of Nephrology, University Clinical Centre Sarajevo over a period of 24 months. The research included determining the following laboratory parameters: serum creatinine, serum albumin, C-reactive protein, leukocytes in the blood, plasma fibrinogen, D-dimer, antithrombin III, coagulation factors VII (FC VII) and coagulation factor VIII (FC VIII). Results: With the progression of kidney disease (CKD stages 1-4), there was a significant increase of inflammatory and procoagulant markers: CRP, fibrinogen and coagulation factor VIII, and an increase in the average values of leukocytes and a reduction in the value of antithrombin III, but without statistical significance. Also, there were no significant differences in the values of D-dimer and coagulation factor VII. Conclusion: The progression of kidney disease is significantly associated with inflammation, which could in the future be useful in prognostic and therapeutic purposes. Connection of CKD with inflammation and proven connection of inflammation with cardiovascular risk indicates the potential value of some biomarkers, which could in the future identify as predictors of outcome and could have the benefit in the early diagnosis and treatment of cardiovascular disease in CKD. PMID:26622082

  15. [Aural polyp in chronic inflammatory middle ear disease].

    PubMed

    López Aguado, D; López Campos, D; Pérez Piñero, B; Campos Bañales, M E

    2003-03-01

    240 patients with chronic otitis media (COM) were studied: 166 ears termed as non cholesteatomatous otitis media and 74 with cholesteatoma. In 38 ears an aural polyp was found with no evidence of cholesteatoma in 19 ears (11.4%) whereas a cholesteatoma was present in the remaining 19 ears. The histology of the polyp and the characteristics of the chronic process were matched: a) The aural polyp is an infrequent complication in COM. b) After histological analysis was found to present two different pictures: The inflammatory reaction polyp, present in non cholesteatomatous COM; and the polyp with granulation tissue and foreign body reaction (keratina) usually found in cholesteatomatous COM. c) The finding of granulation tissue reaction and keratina in an aural polyp is a good predictor for the presence of a cholesteatoma. PMID:12825338

  16. The microbiome in chronic inflammatory airway disease: A threatened species.

    PubMed

    Green, Robin John; Van Niekerk, Andre; Jeevarathnum, Ashley C; Feldman, Charles; Richards On Behalf Of The South African Allergic Rhinitis Working Group, Guy A

    2016-08-01

    The human body is exposed to a multitude of microbes and infectious organisms throughout life. Many of these organisms colonise the skin, gastrointestinal tract (GIT) and airway. We now recognise that this colonisation includes the lower airway, previously thought to be sterile. These colonising organisms play an important role in disease prevention, including an array of chronic inflammatory conditions that are unrelated to infectious diseases. However, new evidence of immune dysregulation suggests that early colonisation, especially of the GITand airway, by pathogenic micro-organisms, has deleterious effects that may contribute to the potential to induce chronic inflammation in young children, which may only express itself in adult life. PMID:27499401

  17. Fibrillary glomerulonephritis combined with chronic inflammatory demyelinating polyneuropathy

    PubMed Central

    Sung, Woo Kyung; Jeong, Jin Uk; Bang, Ki Tae; Shin, Jong Ho; Yoo, Ji Hyung; Kim, Nak Min; Park, Jun Hyung; Kim, Joo Heon

    2015-01-01

    A 58-yr-old man presented with leg edema and subacute weakness of his bilateral lower extremities. Urinary and serum immunoelectrophoresis revealed the presence of lambda-type Bence Jones proteins. He was ultimately diagnosed with monoclonal gammopathy of undetermined significance (MGUS). A renal biopsy specimen showed fibrillary glomerulonephritis (FGN), which was randomly arranged as 12–20 m nonbranching fibrils in the basement membranes. Immunofluorescence studies were negative for immunoglobulin (Ig)G, IgM, IgA, C3, and kappa light chains in the capillary walls and mesangial areas. A Congo red stain for amyloid was negative. Electromyography and nerve conduction velocity examinations results were compatible with the presence of demyelinating polyneuropathy. This case showed a rare combination of FGN, without Ig deposition, and MGUS combined with chronic inflammatory demyelinating polyneuropathy (CIDP). PMID:26484033

  18. [Methylprednisolone pulse in treatment of childhood chronic inflammatory demyelinating polyneuropathy].

    PubMed

    Rafai, M A; Boulaajaj, F Z; Sekkat, Z; El Moutawakkil, B; Slassi, I

    2010-09-01

    Chronic inflammatory demyelinating polyneuropathy (CIDP) in children is rare and treatment is based primarily on intravenous immunoglobulins or oral corticosteroids. Boluses of methylprednisolone (MP) are a possible alternative. We report 3 cases of CIDP in children with good outcome after MP pulse therapy. One male (7 years of age) and 2 females (4 and 5 years of age) presented with recurring episodes of functional impotence of both lower limbs and walking impairment, partially reversible without treatment. Clinical and electrophysiological data and the analysis of the cerebrospinal fluid were compatible with CIDP. MP pulses were administered: the total number of pulses varied from 5 to 8, very satisfactory progression on the clinical and electrophysiological pattern was noted, without recurrence in the 3 cases. Childhood CIDP presents clinical, electrophysiological outcome, and prognostic particularities, recurring readily, and the outcome is good. Boluses of MP are an alternative for treatment of these neuropathies in childhood. PMID:20709511

  19. Coronary microvascular dysfunction in chronic inflammatory rheumatoid diseases.

    PubMed

    Faccini, Alessia; Kaski, Juan Carlos; Camici, Paolo G

    2016-06-14

    Chronic inflammatory rheumatoid diseases (CIRD) such as rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis are an important risk factor for the development of ischaemic heart disease and a source of high cardiovascular morbidity and mortality. In patients affected by CIRD, inflammation can affect coronary microvascular function and contribute to the development of myocardial ischemia and cardiovascular events, even in the absence of obstructive epicardial coronary artery disease. Understanding the molecular aspects that underlie the development of coronary microvascular dysfunction (CMD) in CIRD is of fundamental importance to identify specific therapeutic targets. In this article, we review the pathogenic mechanisms leading to CMD in CIRD, including the controversial results obtained with the use of different therapeutic strategies. We also propose that a practical diagnostic algorithm as the identification of CMD in patients with CIRD may lead to effective measures to prevent the development of angina pectoris and reduce the risk of rapid disease progression. PMID:26912605

  20. Fibrillary glomerulonephritis combined with chronic inflammatory demyelinating polyneuropathy.

    PubMed

    Sung, Woo Kyung; Jeong, Jin Uk; Bang, Ki Tae; Shin, Jong Ho; Yoo, Ji Hyung; Kim, Nak Min; Park, Jun Hyung; Kim, Joo Heon

    2015-06-01

    A 58-yr-old man presented with leg edema and subacute weakness of his bilateral lower extremities. Urinary and serum immunoelectrophoresis revealed the presence of lambda-type Bence Jones proteins. He was ultimately diagnosed with monoclonal gammopathy of undetermined significance (MGUS). A renal biopsy specimen showed fibrillary glomerulonephritis (FGN), which was randomly arranged as 12-20 m nonbranching fibrils in the basement membranes. Immunofluorescence studies were negative for immunoglobulin (Ig)G, IgM, IgA, C3, and kappa light chains in the capillary walls and mesangial areas. A Congo red stain for amyloid was negative. Electromyography and nerve conduction velocity examinations results were compatible with the presence of demyelinating polyneuropathy. This case showed a rare combination of FGN, without Ig deposition, and MGUS combined with chronic inflammatory demyelinating polyneuropathy (CIDP). PMID:26484033

  1. Chronic inflammatory demyelinating polyneuropathy associated with diabetes mellitus

    PubMed Central

    Fatehi, Farzad; Nafissi, Shahriar; Basiri, Keivan; Amiri, Mostafa; Soltanzadeh, Akbar

    2013-01-01

    Various forms of neuropathy are seen diabetic patients; chronic inflammatory demyelinating polyneuropathy (CIDP) seems not to be infrequent neuropathy in patients suffering from diabetes and it seems to be more common than in the general population; on the contrary, some authorities do not support pathogenetic association between diabetes mellitus (DM) and CIDP. Also, there are some controversies on the subject of CIDP treatment in diabetic patients. Some studies showed that patients with CIDP-DM considerably had recovered following treatment with immunotherapeutic modalities like (Intravenous immunoglobulin) IVIG and conversely, some else have argued against the prescription of IVIG in this group and recommend treatment with corticosteroids and provided that resistant, rituximab may be beneficial. The main limitation in most studies is the inadequate number of cases and as a result, problematic decision making in treatment. This article represents an inclusive review of diabetic CIDP presentation and treatment. PMID:24174953

  2. Improving the management of chronic inflammatory demyelinating polyradiculoneuropathy.

    PubMed

    Allen, Jeffrey A; Bril, Vera

    2016-06-01

    This article considers several issues of current interest relating to the management of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), including diagnostic pitfalls, differences between CIDP patients with and without concurrent diabetes mellitus and how to best measure treatment response in daily practice. Despite the availability of diagnostic criteria, many patients diagnosed with CIDP do not meet these criteria; reasons for misdiagnosis are discussed. There are no definitive predictors of treatment response in CIDP; however, certain clinical and electrophysiological characteristics may be helpful. Patients with CIDP and concurrent diabetes present an additional diagnostic challenge; the differences between these groups, including possible differences in response predictors are discussed. Finally, the most appropriate outcome measures for use in daily practice are considered. PMID:27230584

  3. [Subcutaneous immunoglobulin. Treatment in chronic inflammatory demyelinating polyradiculo-neuropathy].

    PubMed

    Nogués, Martín A; Varela, Francisco J; Seminario, Gisela; Insúa, María C; Bezrodnik, Liliana

    2016-01-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired disease that may affect nerve roots and peripheral nerves. Despite its low incidence, diagnosis is particularly important because there are different effective treatments. Human immunoglobulin is one of the mainstays of the treatment. Although there are few studies up to date, subcutaneous immunoglobulin (IgSC) has been proposed as an alternative to intravenous administration with similar efficacy. We present three cases with definite CIDP, classified according to the European Federation of Neurological Societies / Peripheral Nerve, Society (EFNS /PNS) criteria in which was used SCIgG as a treatment after success with the intravenous route. The Overall Neuropathy Limitations Scale (ONLS) was used to estimate the changes in the muscular strength before and after treatment. PMID:26826992

  4. Pathophysiology and biomarkers in chronic inflammatory demyelinating polyradiculoneuropathies.

    PubMed

    Svahn, J; Antoine, J-C; Camdessanché, J-P

    2014-12-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired dysimmune disorder characterized by strong heterogeneity in terms of clinical manifestations, prognostic and response to treatment. To date, its pathophysiology and potential target antigens are not totally identified despite substantial progress in the understanding of the involved molecular mechanisms. Recent researches in the field have underlined the importance of cell-mediated immunity (lymphocytesT CD4+, CD8+ and macrophages), the breakdown of blood-nerve barrier, a failure of T-cell regulation, and the disruption of nodal and paranodal organization at the node of Ranvier. This last point is possibly mediated by autoantibodies towards axoglial adhesion molecules which may disrupt sodium and potassium voltage-gated channels clustering leading to a failure of saltatory conduction and the apparition of conduction blocks. The purpose of this article is to overview the main pathophysiologic mechanisms and biomarkers identified in CIDP. PMID:25459126

  5. The dormant blood microbiome in chronic, inflammatory diseases.

    PubMed

    Potgieter, Marnie; Bester, Janette; Kell, Douglas B; Pretorius, Etheresia

    2015-07-01

    Blood in healthy organisms is seen as a 'sterile' environment: it lacks proliferating microbes. Dormant or not-immediately-culturable forms are not absent, however, as intracellular dormancy is well established. We highlight here that a great many pathogens can survive in blood and inside erythrocytes. 'Non-culturability', reflected by discrepancies between plate counts and total counts, is commonplace in environmental microbiology. It is overcome by improved culturing methods, and we asked how common this would be in blood. A number of recent, sequence-based and ultramicroscopic studies have uncovered an authentic blood microbiome in a number of non-communicable diseases. The chief origin of these microbes is the gut microbiome (especially when it shifts composition to a pathogenic state, known as 'dysbiosis'). Another source is microbes translocated from the oral cavity. 'Dysbiosis' is also used to describe translocation of cells into blood or other tissues. To avoid ambiguity, we here use the term 'atopobiosis' for microbes that appear in places other than their normal location. Atopobiosis may contribute to the dynamics of a variety of inflammatory diseases. Overall, it seems that many more chronic, non-communicable, inflammatory diseases may have a microbial component than are presently considered, and may be treatable using bactericidal antibiotics or vaccines. PMID:25940667

  6. The dormant blood microbiome in chronic, inflammatory diseases

    PubMed Central

    Potgieter, Marnie; Bester, Janette; Kell, Douglas B.; Pretorius, Etheresia

    2015-01-01

    Blood in healthy organisms is seen as a ‘sterile’ environment: it lacks proliferating microbes. Dormant or not-immediately-culturable forms are not absent, however, as intracellular dormancy is well established. We highlight here that a great many pathogens can survive in blood and inside erythrocytes. ‘Non-culturability’, reflected by discrepancies between plate counts and total counts, is commonplace in environmental microbiology. It is overcome by improved culturing methods, and we asked how common this would be in blood. A number of recent, sequence-based and ultramicroscopic studies have uncovered an authentic blood microbiome in a number of non-communicable diseases. The chief origin of these microbes is the gut microbiome (especially when it shifts composition to a pathogenic state, known as ‘dysbiosis’). Another source is microbes translocated from the oral cavity. ‘Dysbiosis’ is also used to describe translocation of cells into blood or other tissues. To avoid ambiguity, we here use the term ‘atopobiosis’ for microbes that appear in places other than their normal location. Atopobiosis may contribute to the dynamics of a variety of inflammatory diseases. Overall, it seems that many more chronic, non-communicable, inflammatory diseases may have a microbial component than are presently considered, and may be treatable using bactericidal antibiotics or vaccines. PMID:25940667

  7. DISREGULATION OF INFLAMMATORY RESPONSES BY CHRONIC CIRCADIAN DISRUPTION

    PubMed Central

    Castanon-Cervantes, Oscar; Wu, Mingwei; Ehlen, J. Christopher; Paul, Ketema; Gamble, Karen L.; Johnson, Russell L.; Besing, Rachel C.; Menaker, Michael; Gewirtz, Andrew T.; Davidson, Alec J.

    2010-01-01

    Circadian rhythms modulate nearly every mammalian physiological process. Chronic disruption of circadian timing in shift work or during chronic jet lag in animal models leads to a higher risk of several pathologies. Many of these conditions in both shift workers and experimental models share the common risk factor of inflammation. Here we show that experimentally-induced circadian disruption altered innate immune responses. Endotoxemic shock induced by LPS was magnified leading to hypothermia and death after 4 consecutive weekly 6h phase-advances of the light-dark schedule, with 89% mortality compared with 21% in unshifted control mice. This may be due to a heightened release of pro-inflammatory cytokines in response to LPS treatment in shifted animals. Isolated peritoneal macrophages harvested from shifted mice exhibited a similarly heightened response to LPS in vitro, indicating that these cells are a target for jet lag. Sleep deprivation and stress are known to alter immune function and are potential mediators of the effects we describe. However polysomnographic recording in mice exposed to the shifting schedule revealed no sleep loss, and stress measures were not altered in shifted mice. In contrast, we observed altered or abolished rhythms in the expression of clock genes in the central clock, liver, thymus and peritoneal macrophages in mice after chronic jet lag. We conclude that circadian disruption, but not sleep loss or stress, are associated with jet lag-related disregulation of the innate immune system. Such immune changes might be a common mechanism for the myriad negative health effects of shift work. PMID:20944004

  8. Atherosclerotic cardiovascular disease in patients with chronic inflammatory joint disorders.

    PubMed

    Agca, R; Heslinga, S C; van Halm, V P; Nurmohamed, M T

    2016-05-15

    Inflammatory joint disorders (IJD), including rheumatoid arthritis (RA), ankylosing spondylitis (ASp) and psoriatic arthritis (PsA), are prevalent conditions worldwide with a considerable burden on healthcare systems. IJD are associated with increased cardiovascular (CV) disease-related morbidity and mortality. In this review, we present an overview of the literature. Standardised mortality ratios are increased in IJD compared with the general population, that is, RA 1.3-2.3, ASp 1.6-1.9 and PsA 0.8-1.6. This premature mortality is mainly caused by atherosclerotic events. In RA, this CV risk is comparable to that in type 2 diabetes. Traditional CV risk factors are more often present and partially a consequence of changes in physical function related to the underlying IJD. Also, chronic systemic inflammation itself is an independent CV risk factor. Optimal control of disease activity with conventional synthetic, targeted synthetic and biological disease-modifying antirheumatic drugs decreases this excess risk. High-grade inflammation as well as anti-inflammatory treatment alter traditional CV risk factors, such as lipids. In view of the above-mentioned CV burden in patients with IJD, CV risk management is necessary. Presently, this CV risk management is still lacking in usual care. Patients, general practitioners, cardiologists, internists and rheumatologists need to be aware of the substantially increased CV risk in IJD and should make a combined effort to timely initiate CV risk management in accordance with prevailing guidelines together with optimal control of rheumatic disease activity. CV screening and treatment strategies need to be implemented in usual care. PMID:26888573

  9. Inflammatory mechanisms in patients with chronic obstructive pulmonary disease.

    PubMed

    Barnes, Peter J

    2016-07-01

    Chronic obstructive pulmonary disease (COPD) is associated with chronic inflammation affecting predominantly the lung parenchyma and peripheral airways that results in largely irreversible and progressive airflow limitation. This inflammation is characterized by increased numbers of alveolar macrophages, neutrophils, T lymphocytes (predominantly TC1, TH1, and TH17 cells), and innate lymphoid cells recruited from the circulation. These cells and structural cells, including epithelial and endothelial cells and fibroblasts, secrete a variety of proinflammatory mediators, including cytokines, chemokines, growth factors, and lipid mediators. Although most patients with COPD have a predominantly neutrophilic inflammation, some have an increase in eosinophil counts, which might be orchestrated by TH2 cells and type 2 innate lymphoid cells though release of IL-33 from epithelial cells. These patients might be more responsive to corticosteroids and bronchodilators. Oxidative stress plays a key role in driving COPD-related inflammation, even in ex-smokers, and might result in activation of the proinflammatory transcription factor nuclear factor κB (NF-κB), impaired antiprotease defenses, DNA damage, cellular senescence, autoantibody generation, and corticosteroid resistance though inactivation of histone deacetylase 2. Systemic inflammation is also found in patients with COPD and can worsen comorbidities, such as cardiovascular diseases, diabetes, and osteoporosis. Accelerated aging in the lungs of patients with COPD can also generate inflammatory protein release from senescent cells in the lung. In the future, it will be important to recognize phenotypes of patients with optimal responses to more specific therapies, and development of biomarkers that identify the therapeutic phenotypes will be important. PMID:27373322

  10. Chronic Inflammatory Disease and Osteopathy: A Systematic Review

    PubMed Central

    Cicchitti, Luca; Martelli, Marta; Cerritelli, Francesco

    2015-01-01

    Background Chronic inflammatory diseases (CID) are globally highly prevalent and characterized by severe pathological medical conditions. Several trials were conducted aiming at measuring the effects of manipulative therapies on patients affected by CID. The purpose of this review was to explore the extent to which osteopathic manipulative treatment (OMT) can be benefi-cial in medical conditions also classified as CID. Methods This review included any type of experimental study which enrolled sub-jects with CID comparing OMT with any type of control procedure. The search was conducted on eight databases in January 2014 using a pragmatic literature search approach. Two independent re-viewers conducted study selection and data extraction for each study. The risk of bias was evaluated according to the Cochrane methods. Heterogeneity was assessed and meta-analysis performed where possible. Results 10 studies met the inclusion criteria for this review enrolling 386 subjects. The search identified six RCTs, one laboratory study, one cross-over pilot studies, one observation-al study and one case control pilot study. Results suggest a potential effect of osteopathic medicine on patients with medical pathologies associated with CID (in particular Chronic Obstructive Pul-monary Disease (COPD), Irritable Bowel Syndrome, Asthma and Peripheral Arterial Disease) com-pared to no treatment or sham therapy although data remain elusive. Moreover one study showed possible effects on arthritis rat model. Meta-analysis was performed for COPD studies only show-ing no effect of any type of OMT applied versus control. No major side effects were reported by those receiving OMT. Conclusion The present systematic review showed inconsistent data on the effect of OMT in the treatment of medical conditions potentially associated with CID, however the OMT appears to be a safe approach. Further more robust trials are needed to determine the direction and magnitude of the effect of OMT and to

  11. Electrophysiological features of POEMS syndrome and chronic inflammatory demyelinating polyneuropathy.

    PubMed

    Guo, Xiuming; Qin, Xinyue; Zhang, Yuping; Huang, Cheng; Yu, Gang

    2014-04-01

    Polyneuropathy is often an initial manifestation of polyneuropathy, organomegaly, endocrinopathy, M protein and skin changes (POEMS) syndrome and therefore this disorder is frequently misdiagnosed as chronic inflammatory demyelinating polyneuropathy (CIDP). We reviewed electrophysiological data in 20 patients with POEMS syndrome and 36 matched patients with CIDP to compare the electrophysiological features of POEMS syndrome and CIDP. Compared with CIDP controls, POEMS patients demonstrated (1) less prolonged distal motor latency and less reduced motor nerve and sensory nerve conduction velocities, (2) greater reduction of amplitudes of compound motor action potentials (CMAP) in distal stimulation, and similar reduction of amplitudes of CMAP in proximal stimulation, (3) similar reduction of amplitudes of sensory nerve action potentials (SNAP) in median and ulnar nerves, and a greater reduction of amplitudes of SNAP in tibial and peroneal nerves, (4) less temporal dispersion, (5) less frequent conduction block, (6) more frequent neurogenic injury in the muscles of the upper and lower limbs, and more frequent neurogenic injury in the muscles of the lower than upper limbs, (7) similar F wave and H reflex abnormalities, and (8) less frequent skin sympathetic response abnormalities. We concluded that before development of typical clinical manifestations, POEMS neuropathy can be distinguished from CIDP by neural electrophysiological examination. These electrophysiological features can be used for early diagnosis and initiating correct treatment of POEMS syndrome. PMID:24268501

  12. Stance Postural Strategies in Patients with Chronic Inflammatory Demyelinating Polyradiculoneuropathy

    PubMed Central

    Missori, Paolo; Trompetto, Carlo; Fattapposta, Francesco

    2016-01-01

    Introduction Polyneuropathy leads to postural instability and an increased risk of falling. We investigated how impaired motor impairment and proprioceptive input due to neuropathy influences postural strategies. Methods Platformless bisegmental posturography data were recorded in healthy subjects and patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Each subject stood on the floor, wore a head and a hip electromagnetic tracker. Sway amplitude and velocity were recorded and the mean direction difference (MDD) in the velocity vector between trackers was calculated as a flexibility index. Results Head and hip postural sway increased more in patients with CIDP than in healthy controls. MDD values reflecting hip strategies also increased more in patients than in controls. In the eyes closed condition MDD values in healthy subjects decreased but in patients remained unchanged. Discussion Sensori-motor impairment changes the balance between postural strategies that patients adopt to maintain upright quiet stance. Motor impairment leads to hip postural strategy overweight (eyes open), and prevents strategy re-balancing when the sensory context predominantly relies on proprioceptive input (eyes closed). PMID:26977594

  13. Human Endogenous Retrovirus and Neuroinflammation in Chronic Inflammatory Demyelinating Polyradiculoneuropathy

    PubMed Central

    Faucard, Raphaël; Madeira, Alexandra; Gehin, Nadège; Authier, François-Jérôme; Panaite, Petrica-Adrian; Lesage, Catherine; Burgelin, Ingrid; Bertel, Mélanie; Bernard, Corinne; Curtin, François; Lang, Aloïs B.; Steck, Andreas J.; Perron, Hervé; Kuntzer, Thierry; Créange, Alain

    2016-01-01

    Background Human endogenous retroviruses HERV-W encode a pro-inflammatory protein, named MSRV-Env from its original identification in Multiple Sclerosis. Though not detected in various neurological controls, MSRV-Env was found in patients with chronic inflammatory demyelinating polyradiculoneuropathies (CIDPs). This study investigated the expression of MSRV in CIDP and evaluated relevant MSRV-Env pathogenic effects. Methods 50 CIDP patients, 19 other neurological controls (ONDs) and 65 healthy blood donors (HBDs) were recruited from two different countries. MSRV-env and -pol transcripts, IL6 and CXCL10 levels were quantified from blood samples. MSRV-Env immunohistology was performed in distal sensory nerves from CIDP and neurological controls biopsies. MSRV-Env pathogenic effects and mode of action were assayed in cultured primary human Schwann cells (HSCs). Findings In both cohorts, MSRV-env and -pol transcripts, IL6 positivity prevalence and CXCL10 levels were significantly elevated in CIDP patients when compared to HBDs and ONDs (statistically significant in all comparisons). MSRV-Env protein was detected in Schwann cells in 5/7 CIDP biopsies. HSC exposed to or transfected with MSRV-env presented a strong increase of IL6 and CXCL10 transcripts and protein secretion. These pathogenic effects on HSC were inhibited by GNbAC1, a highly specific and neutralizing humanized monoclonal antibody targeting MSRV-Env. Interpretation The present study showed that MSRV-Env may trigger the release of critical immune mediators proposed as instrumental factors involved in the pathophysiology of CIDP. Significant MSRV-Env expression was detected in a significant proportion of patients with CIDP, in which it may play a role according to its presently observed effects on Schwann cells along with previously known effects on immune cells. Experimental results also suggest that a biomarker-driven therapeutic strategy targeting this protein with a neutralizing antibody such as GNbAC1

  14. [Role of non-coding regulatory ribonucleic acids in chronic inflammatory diseases].

    PubMed

    Heinz, G A; Mashreghi, M-F

    2016-05-01

    Non-coding regulatory ribonucleic acids (RNA), including microRNA, long non-coding RNA and circular RNA, can influence the expression of genes mediating inflammatory processes and therefore affect the course and progression of chronic inflammatory diseases. Recent studies using antisense oligonucleotides suggest that such non-coding regulatory RNAs are suitable as novel therapeutic target molecules for the treatment of inflammatory rheumatic diseases. PMID:27115697

  15. Chronic inflammatory systemic diseases: An evolutionary trade-off between acutely beneficial but chronically harmful programs.

    PubMed

    Straub, Rainer H; Schradin, Carsten

    2016-01-01

    It has been recognized that during chronic inflammatory systemic diseases (CIDs) maladaptations of the immune, nervous, endocrine and reproductive system occur. Maladaptation leads to disease sequelae in CIDs. The ultimate reason of disease sequelae in CIDs remained unclear because clinicians do not consider bodily energy trade-offs and evolutionary medicine. We review the evolution of physiological supersystems, fitness consequences of genes involved in CIDs during different life-history stages, environmental factors of CIDs, energy trade-offs during inflammatory episodes and the non-specificity of CIDs. Incorporating bodily energy regulation into evolutionary medicine builds a framework to better understand pathophysiology of CIDs by considering that genes and networks used are positively selected if they serve acute, highly energy-consuming inflammation. It is predicted that genes that protect energy stores are positively selected (as immune memory). This could explain why energy-demanding inflammatory episodes like infectious diseases must be terminated within 3-8 weeks to be adaptive, and otherwise become maladaptive. Considering energy regulation as an evolved adaptive trait explains why many known sequelae of different CIDs must be uniform. These are, e.g. sickness behavior/fatigue/depressive symptoms, sleep disturbance, anorexia, malnutrition, muscle wasting-cachexia, cachectic obesity, insulin resistance with hyperinsulinemia, dyslipidemia, alterations of steroid hormone axes, disturbances of the hypothalamic-pituitary-gonadal (HPG) axis, hypertension, bone loss and hypercoagulability. Considering evolved energy trade-offs helps us to understand how an energy imbalance can lead to the disease sequelae of CIDs. In the future, clinicians must translate this knowledge into early diagnosis and symptomatic treatment in CIDs. PMID:26817483

  16. Clinical application of expectorant therapy in chronic inflammatory airway diseases (Review)

    PubMed Central

    ZHANG, TING; ZHOU, XIANGDONG

    2014-01-01

    Airway mucus hypersecretion is a significant clinical and pathological feature of chronic inflammatory airway diseases. Its clinical presentations include recurrent coughing and phlegm. Airway mucus is closely associated with the occurrence, development and prognosis of chronic inflammatory airway diseases and critically affects the lung function, quality of life, hospitalization rate and mortality of patients with chronic inflammatory airway diseases. Therefore, expectorant therapies targeting the potential mechanisms of mucus hypersecretion have been the focus of numerous studies. Conventional expectorants are mainly mucoactive medicines, including nausea-stimulating expectorants, mucolytics, mucokinetics, and proteases and nucleases. In addition, certain traditional Chinese herbal medicines and non-mucoactive agents, including muscarinic acetylcholine receptor antagonists, corticosteroids, leukotriene receptor antagonists and macrolide antibiotics, have also shown expectorant effects. Several novel medicines for expectorant therapy have emerged, including cholesterol-lowering statins, epidermal growth factor receptor tyrosine kinase inhibitors, phosphodiesterase-4 inhibitors, stanozolol, surfactants, flavonoids, tachykinin receptor antagonists, protease inhibitors, cytokine antagonists and purinergic agonists. With the increasing number of multidisciplinary studies, the effectiveness of expectorant therapy for the treatment of chronic inflammatory airway diseases has been confirmed. Therefore, the development of novel expectorants and the standardization of expectorant therapy are the direction and focus of future studies, thus benefiting patients who have a chronic inflammatory airway disease. PMID:24660026

  17. Pathogenic Th cell subsets in chronic inflammatory diseases.

    PubMed

    Kumagai, Jin; Hirahara, Kiyoshi; Nakayama, Toshinori

    2016-01-01

      CD4(+) T cells play central roles to appropriate protection against pathogens. While, they can also be pathogenic driving inflammatory diseases. Besides the classical model of differentiation of T helper 1 (Th1) and Th2 cells, various CD4(+) T cell subsets, including Th17, Th9, T follicular helper (Tfh) and T regulatory (Treg) cells, have been recognized recently. In this review, we will focus on how these various CD4(+) T cell subsets contribute to the pathogenesis of immune-mediated inflammatory diseases. We will also discuss various unique subpopulations of T helper cells that have been identified. Recent advancement of the basic immunological research revealed that T helper cells are plastic than we imagined. So, we will focus on the molecular mechanisms underlying the generation of the plasticity and heterogeneity of T helper cell subsets. These latest finding regarding T helper cell subsets has pushed us to reconsider the etiology of immune-mediated inflammatory diseases beyond the model based on the conventional Th1/Th2 balance. Toward this end, we put forward another model, "the pathogenic Th population disease induction model", as a possible mechanism for the induction and/or persistence of immune-mediated inflammatory diseases. PMID:27212597

  18. Contactin 1 IgG4 associates to chronic inflammatory demyelinating polyneuropathy with sensory ataxia

    PubMed Central

    Miura, Yumako; Devaux, Jérôme J.; Fukami, Yuki; Manso, Constance; Belghazi, Maya; Wong, Anna Hiu Yi

    2015-01-01

    A Spanish group recently reported that four patients with chronic inflammatory demyelinating polyneuropathy carrying IgG4 autoantibodies against contactin 1 showed aggressive symptom onset and poor response to intravenous immunoglobulin. We aimed to describe the clinical and serological features of Japanese chronic inflammatory demyelinating polyneuropathy patients displaying the anti-contactin 1 antibodies. Thirteen of 533 (2.4%) patients with chronic inflammatory demyelinating polyneuropathy had anti-contactin 1 IgG4 whereas neither patients from disease or normal control subjects did (P = 0.02). Three of 13 (23%) patients showed subacute symptom onset, but all of the patients presented with sensory ataxia. Six of 10 (60%) anti-contactin 1 antibody-positive patients had poor response to intravenous immunoglobulin, whereas 8 of 11 (73%) antibody-positive patients had good response to corticosteroids. Anti-contactin 1 IgG4 antibodies are a possible biomarker to guide treatment option. PMID:25808373

  19. The contribution of natural selection to present-day susceptibility to chronic inflammatory and autoimmune disease

    PubMed Central

    Brinkworth, Jessica F; Barreiro, Luis B

    2015-01-01

    Chronic inflammatory and autoimmune diseases have been the focus of many genome-wide association studies (GWAS) because they represent a significant cause of illness and morbidity, and many are heritable. Almost a decade of GWAS studies suggests that the pathological inflammation associated with these diseases is controlled by a limited number of networked immune system genes. Chronic inflammatory and autoimmune diseases are enigmatic from an evolutionary perspective because they exert a negative affect on reproductive fitness. The persistence of these conditions may be partially explained by the important roles the implicated immune genes play in pathogen defense and other functions thought to be under strong natural selection in humans. The evolutionary reasons for chronic inflammatory and autoimmune disease persistence and uneven distribution across populations are the focus of this review. PMID:25458997

  20. Health-related quality of life in chronic inflammatory neuropathies: a systematic review.

    PubMed

    Rajabally, Yusuf A; Cavanna, Andrea E

    2015-01-15

    Chronic inflammatory neuropathies represent a heterogeneous group of disorders which affect patients' functional status and quality of life. We conducted a systematic review of the scientific literature on the effects of both disease and treatment interventions on health-related quality of life (HRQoL) in this patient population. The available data are limited, as few studies have systematically considered HRQoL in patients with inflammatory neuropathies. Moreover, in treatment trials, HRQoL measures have exclusively been used as secondary outcome measures. There is some evidence suggesting that baseline pre-treatment HRQoL reports are lower in patients with chronic inflammatory neuropathy than in age and gender-matched controls. Following treatment interventions, improvements in self-reported measures were consistently documented in the physical domain of HRQoL, which in turn correlated with improvements in traditional strength and functional scales. The impact of available treatments on the quality of life of patients with inflammatory neuropathies remains largely under-investigated. Interestingly, recent, although limited evidence from generic HRQoL measures may partly or completely contradict the results found with the primary, traditional outcome measures used (rituximab for anti-MAG neuropathy; immunoglobulins versus corticosteroids for chronic inflammatory demyelinating polyneuropathy). Similarly, HRQoL measures may suggest superiority, rather than equivalence, of certain drug administration methods (subcutaneous over intravenous immunoglobulins). Further research is needed to assess HRQOL in patients with untreated chronic inflammatory neuropathies in comparison to normative values, as well as precisely quantify treatment benefit. The role of both generic and disease-specific HRQoL measures in the evaluation of patients with chronic inflammatory neuropathies is also worthy of further consideration. PMID:25467139

  1. Mesenchymal stromal cells and chronic inflammatory bowel disease.

    PubMed

    Algeri, M; Conforti, A; Pitisci, A; Starc, N; Tomao, L; Bernardo, M E; Locatelli, F

    2015-12-01

    Recent experimental findings have shown the ability of mesenchymal stromal cells (MSCs) to home to damaged tissues and to produce paracrine factors with anti-inflammatory properties, potentially resulting in reduction of inflammation and functional recovery of the damaged tissues. Prompted by these intriguing properties and on the basis of encouraging preclinical data, MSCs are currently being studied in several immune-mediated disorders. Inflammatory bowel diseases (IBD) represent a setting in which MSCs-based therapy has been extensively investigated. Phase I and II studies have documented the safety and feasibility of MSCs. However, efficacy results have so far been conflicting. In this review, we will discuss the biologic rationale that makes MSCs a promising therapeutic tool for IBD, and analyze recent experimental and clinical findings, highlighting current limitations and future perspectives of MSCs-related immunotherapy for IBD. PMID:26170204

  2. The role of antimicrobial peptides in chronic inflammatory skin diseases

    PubMed Central

    Majewski, Sławomir

    2016-01-01

    Antimicrobial peptides (AMPs) are effector molecules of the innate immune system of the skin. They present an activity against a broad spectrum of Gram-positive and Gram-negative bacteria as well as some fungi, parasites and enveloped viruses. Several inflammatory skin diseases including psoriasis, atopic dermatitis, acne vulgaris and rosacea are characterized by a dysregulated expression of AMPs. Antimicrobial peptides are excessively produced in lesional psoriatic scales or rosacea in contrast to the atopic skin that shows lower AMP levels when compared with psoriasis. The importance of the AMPs contribution to host immunity is indisputable as alterations in the antimicrobial peptide expression have been associated with various pathologic processes. This review discusses the biology and clinical relevance of antimicrobial peptides expressed in the skin and their role in the pathogenesis of inflammatory skin diseases. PMID:26985172

  3. The role of antimicrobial peptides in chronic inflammatory skin diseases.

    PubMed

    Marcinkiewicz, Małgorzata; Majewski, Sławomir

    2016-02-01

    Antimicrobial peptides (AMPs) are effector molecules of the innate immune system of the skin. They present an activity against a broad spectrum of Gram-positive and Gram-negative bacteria as well as some fungi, parasites and enveloped viruses. Several inflammatory skin diseases including psoriasis, atopic dermatitis, acne vulgaris and rosacea are characterized by a dysregulated expression of AMPs. Antimicrobial peptides are excessively produced in lesional psoriatic scales or rosacea in contrast to the atopic skin that shows lower AMP levels when compared with psoriasis. The importance of the AMPs contribution to host immunity is indisputable as alterations in the antimicrobial peptide expression have been associated with various pathologic processes. This review discusses the biology and clinical relevance of antimicrobial peptides expressed in the skin and their role in the pathogenesis of inflammatory skin diseases. PMID:26985172

  4. Inflammatory mediators in chronic otitis media with effusion.

    PubMed

    Skoner, D P; Stillwagon, P K; Casselbrandt, M L; Tanner, E P; Doyle, W J; Fireman, P

    1988-10-01

    Otitis media with effusion (OME) is a common middle ear inflammatory disease in the pediatric population. This article determines concentrations of three functionally and metabolically distinct inflammatory mediators in middle ear effusions (MEE) and corresponding plasma of children with OME. One hundred two patients (mean age, 4.9 years) with persistent OME were studied. Middle ear effusions were collected from all subjects and plasma from a subset at the time of tympanostomy tube insertion. Histamine was assayed radioisotopically, 13,14-dihydro-15-keto-prostaglandin F2 alpha (stable PGF2 alpha metabolite) by radioimmunoassay, and neutrophil chemotactic factor of anaphylaxis by modified Boyden chamber. Mean MEE levels of the mediators (39 +/- 13 ng/mL, 462 +/- 179 pg/mL, and 264% +/- 57% positive control, respectively) were markedly higher than those of corresponding plasma (0.5 +/- 0.1 ng/mL, 285 +/- 127 pg/mL, and 47% +/- 5% positive control, respectively). The mean histamine content of mucoid effusions (43.2 +/- 56.9 ng/mL) was significantly higher than that of purulent (22.5 +/- 10.5 ng/mL) and serous (17.9 +/- 16.8 ng/mL) effusions. Higher histamine levels were observed in effusions positive for Haemophilus influenzae when compared with those with other pathogenic isolates. The high concentrations of these mediators in MEE and their potential for inducing or sustaining the inflammatory process supports a role in the pathogenesis of OME. PMID:3046637

  5. Atherosclerosis: a chronic inflammatory disease mediated by mast cells.

    PubMed

    Conti, Pio; Shaik-Dasthagirisaeb, Yazdami

    2015-01-01

    Inflammation is a process that plays an important role in the initiation and progression of atherosclerosis and immune disease, involving multiple cell types, including macrophages, T-lymphocytes, endothelial cells, smooth muscle cells and mast cells. The fundamental damage of atherosclerosis is the atheromatous or fibro-fatty plaque which is a lesion that causes several diseases. In atherosclerosis the innate immune response, which involves macrophages, is initiated by the arterial endothelial cells which respond to modified lipoproteins and lead to Th1 cell subset activation and generation of inflammatory cytokines and chemoattractant chemokines. Other immune cells, such as CD4+ T inflammatory cells, which play a critical role in the development and progression of atherosclerosis, and regulatory T cells [Treg], which have a protective effect on the development of atherosclerosis are involved. Considerable evidence indicates that mast cells and their products play a key role in inflammation and atherosclerosis. Activated mast cells can have detrimental effects, provoking matrix degradation, apoptosis, and enhancement as well as recruitment of inflammatory cells, which actively contributes to atherosclerosis and plaque formation. Here we discuss the relationship between atherosclerosis, inflammation and mast cells. PMID:26648785

  6. Atherosclerosis: a chronic inflammatory disease mediated by mast cells

    PubMed Central

    Shaik-Dasthagirisaeb, Yazdami

    2015-01-01

    Inflammation is a process that plays an important role in the initiation and progression of atherosclerosis and immune disease, involving multiple cell types, including macrophages, T-lymphocytes, endothelial cells, smooth muscle cells and mast cells. The fundamental damage of atherosclerosis is the atheromatous or fibro-fatty plaque which is a lesion that causes several diseases. In atherosclerosis the innate immune response, which involves macrophages, is initiated by the arterial endothelial cells which respond to modified lipoproteins and lead to Th1 cell subset activation and generation of inflammatory cytokines and chemoattractant chemokines. Other immune cells, such as CD4+ T inflammatory cells, which play a critical role in the development and progression of atherosclerosis, and regulatory T cells [Treg], which have a protective effect on the development of atherosclerosis are involved. Considerable evidence indicates that mast cells and their products play a key role in inflammation and atherosclerosis. Activated mast cells can have detrimental effects, provoking matrix degradation, apoptosis, and enhancement as well as recruitment of inflammatory cells, which actively contributes to atherosclerosis and plaque formation. Here we discuss the relationship between atherosclerosis, inflammation and mast cells. PMID:26648785

  7. Ileal inflammatory fibroid polyp causing chronic ileocolic intussusception and mimicking cecal carcinoma

    PubMed Central

    Gara, Naveen; Falzarano, John S; Limm, Whitney ML; Namiki, Thomas S; Tom, Laurie KS

    2009-01-01

    Inflammatory fibroid polyp (IFP) is a rare, idiopathic pseudotumorous lesion of the gastrointestinal tract. While mostly reported as solitary gastric lesions, multiple cases of small bowel IFPs are also reported. It is a documented cause of intussusception in adults. In the case reports of ileal inflammatory fibroid polyps with intussusception, an emergent presentation with small bowel obstruction has been most often described. Here we depict a case of ileal inflammatory fibroid polyp presenting with chronic intermittent ileocolic intussusception, anemia and weight loss with an endoscopic appearance mimicking necrotic cecal carcinoma. PMID:21160780

  8. Dysautonomic polyneuropathy as a variant of chronic inflammatory "demyelinating" polyneuropathy?

    PubMed

    Wolf, Hans-Heinrich; Kornhuber, Malte Erich; Weis, Joachim; Posa, Andreas

    2016-08-01

    This report describes the clinical course over almost one decade of a male patient presenting with immune-mediated pure autonomic neuropathy resembling a distinct variant of chronic dysimmune polyneuropathies. We suppose autoantibodies directed against epitopes on autonomic axons or neurons causative for the symptoms. PMID:27379500

  9. Chronic Q Fever with No Elevation of Inflammatory Markers: A Case Report

    PubMed Central

    Boattini, Matteo; Almeida, André; Moura, Rita Barata; Abreu, João; Santos, Ana Sofia; Toscano Rico, Miguel

    2012-01-01

    We describe the case of a 55-year-old man with a biological prosthetic aortic valve who suffered from epigastrium and right hypochondrium pain associated with intermittent night sweats. Liver biopsy showed infectious hepatitis pattern without pathognomonic features. Coxiella burnetii serology was suggestive of chronic Q fever, and modified Duke's criteria for endocarditis were also fulfilled. The authors present a brief literature review concerning chronic Q fever, emphasizing absent previous reports of chronic Q fever with hepatitis and endocarditis and no increase in inflammatory markers. PMID:22792113

  10. Early Severe Inflammatory Responses to Uropathogenic E. coli Predispose to Chronic and Recurrent Urinary Tract Infection

    PubMed Central

    Hannan, Thomas J.; Mysorekar, Indira U.; Hung, Chia S.; Isaacson-Schmid, Megan L.; Hultgren, Scott J.

    2010-01-01

    Chronic infections are an increasing problem due to the aging population and the increase in antibiotic resistant organisms. Therefore, understanding the host-pathogen interactions that result in chronic infection is of great importance. Here, we investigate the molecular basis of chronic bacterial cystitis. We establish that introduction of uropathogenic E. coli (UPEC) into the bladders of C3H mice results in two distinct disease outcomes: resolution of acute infection or development of chronic cystitis lasting months. The incidence of chronic cystitis is both host strain and infectious dose-dependent. Further, development of chronic cystitis is preceded by biomarkers of local and systemic acute inflammation at 24 hours post-infection, including severe pyuria and bladder inflammation with mucosal injury, and a distinct serum cytokine signature consisting of elevated IL-5, IL-6, G-CSF, and the IL-8 analog KC. Mice deficient in TLR4 signaling or lymphocytes lack these innate responses and are resistant, to varying degrees, to developing chronic cystitis. Treatment of C3H mice with the glucocorticoid anti-inflammatory drug dexamethasone prior to UPEC infection also suppresses the development of chronic cystitis. Finally, individuals with a history of chronic cystitis, lasting at least 14 days, are significantly more susceptible to redeveloping severe, chronic cystitis upon bacterial challenge. Thus, we have discovered that the development of chronic cystitis in C3H mice by UPEC is facilitated by severe acute inflammatory responses early in infection, which subsequently are predisposing to recurrent cystitis, an insidious problem in women. Overall, these results have significant implications for our understanding of how early host-pathogen interactions at the mucosal surface determines the fate of disease. PMID:20811584

  11. Association of inflammatory bowel disease risk loci with sarcoidosis, and its acute and chronic subphenotypes.

    PubMed

    Fischer, A; Nothnagel, M; Franke, A; Jacobs, G; Saadati, H R; Gaede, K I; Rosenstiel, P; Schürmann, M; Müller-Quernheim, J; Schreiber, S; Hofmann, S

    2011-03-01

    Sarcoidosis is a complex granulomatous inflammatory disorder that shares several clinical and pathogenic features with inflammatory bowel disease (IBD). Postulating a common genetic basis of inflammatory diseases, we tested 106 single-nucleotide polymorphisms (SNPs) that are known or have been suggested to be associated with IBD for a potential association with sarcoidosis and its acute and chronic subphenotypes. We genotyped 1,996 German sarcoidosis patients, comprising 648 acutely and 1,161 chronically affected individuals, 2,622 control subjects, and 342 German trios with affected offspring using SNPlex™ technology. The nonsynonymous SNP rs11209026 (Arg381Gln) in the interleukin (IL)-23 receptor (IL23R) gene was associated with chronic sarcoidosis (OR 0.63; p = 5.58×10(-5)), which was supported by the result of a transmission disequilibrium test analysis in the independent family sample (OR 0.50; p = 0.031). Marker rs12035082 located at chromosome 1q24.3 was found to be associated with the acute subphenotype (OR 1.36; p = 6.80×10(-7)) and rs916977 (HERC2 locus; OR 1.30; p = 4.49×10(-5)) was associated with sarcoidosis. Our results highlight the potential importance of the IL-23 signalling pathway for the development of chronic sarcoidosis. The finding links sarcoidosis pathogenesis to other inflammatory conditions and may contribute to new hypotheses on disease mechanisms. PMID:20650992

  12. Progressive chronic inflammatory demyelinating polyneuropathy in a child with central nervous system involvement and myopathy.

    PubMed

    Barisić, Nina; Horvath, Rita; Grković, Lana; Mihelcić, Dina; Luetić, Tomislav

    2006-12-01

    Chronic inflammatory demyelinating polyneuropathy (CIDP) is a chronic disorder, manifesting with monophasic or relapsing course. Progressive course is rare in children. The article presents a boy with progressive generalized muscle weakness and areflexia since the age of two, developed after viral infection. Electromyoneurography showed severe neurogenic lesion, with myopathic pattern in proximal muscles. Increased serum ganglioside antibody titers (anti-GM1 and anti-GD1b) were registered. Sural nerve biopsy revealed demyelination and onion bulbs. Inflammatory perivascular CD3 positive infiltrates were present in muscle and nerve biopsies. Brain magnetic resonance imaging showed cortical atrophy, hyperintensities of the white matter and gray matter hypointensities. Improvement occurred on intravenous immune globulins and methylprednisolone treatment. Demyelination might develop in central and peripheral nervous system associated with inflammatory myopathy in patients with progressive course of CIDP. PMID:17243577

  13. [Ultrasonography in chronic inflammatory rheumatic and connective tissue disorders].

    PubMed

    Mérot, O; Le Goff, B

    2014-08-01

    Musculoskeletal ultrasonography is now widely used by almost all rheumatologists thanks to an improvement in the quality of ultrasound unit and probe and to the systematic teaching of this imaging technique to the rheumatology fellows. Applications have broadened from the study of degenerative and mechanical diseases to inflammatory rheumatic diseases. Ultrasound is more sensitive than clinical examination. Power Doppler allows the direct visualisation of inflammation within the tissues. Finally, it is a prognostic tool helping the physician in the management of the disease. This review will focus on the value and applications of ultrasonography in the 2 most frequent rheumatic diseases: rheumatoid arthritis and spondyloarthritis. We will also give some recent data on the usefulness of this imaging technique in the study of musculoskeletal manifestations associated with connective tissue disease. PMID:24439720

  14. Identification of Novel Anti-inflammatory Agents from Ayurvedic Medicine for Prevention of Chronic Diseases

    PubMed Central

    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

    2011-01-01

    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-κB) that controls over 500 different gene products, has emerged as major mediator of inflammation. Thus agents that can inhibit NF-κB 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 6000 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. PMID:21561421

  15. Mitochondrial dysfunction in inflammatory responses and cellular senescence: pathogenesis and pharmacological targets for chronic lung diseases.

    PubMed

    Yue, Li; Yao, Hongwei

    2016-08-01

    Mitochondria are dynamic organelles, which couple the various cellular processes that regulate metabolism, cell proliferation and survival. Environmental stress can cause mitochondrial dysfunction and dynamic changes including reduced mitochondrial biogenesis, oxidative phosphorylation and ATP production, as well as mitophagy impairment, which leads to increased ROS, inflammatory responses and cellular senescence. Oxidative stress, inflammation and cellular senescence all have important roles in the pathogenesis of chronic lung diseases, such as chronic obstructive pulmonary disease, pulmonary fibrosis and bronchopulmonary dysplasia. In this review, we discuss the current state on how mitochondrial dysfunction affects inflammatory responses and cellular senescence, the mechanisms of mitochondrial dysfunction underlying the pathogenesis of chronic lung diseases and the potential of mitochondrial transfer and replacement as treatments for these diseases. PMID:27189175

  16. Dissociated sterol-based liver X receptor agonists as therapeutics for chronic inflammatory diseases.

    PubMed

    Yu, Shan; Li, Sijia; Henke, Adam; Muse, Evan D; Cheng, Bo; Welzel, Gustav; Chatterjee, Arnab K; Wang, Danling; Roland, Jason; Glass, Christopher K; Tremblay, Matthew

    2016-07-01

    Liver X receptor (LXR), a nuclear hormone receptor, is an essential regulator of immune responses. Activation of LXR-mediated transcription by synthetic agonists, such as T0901317 and GW3965, attenuates progression of inflammatory disease in animal models. However, the adverse effects of these conventional LXR agonists in elevating liver lipids have impeded exploitation of this intriguing mechanism for chronic therapy. Here, we explore the ability of a series of sterol-based LXR agonists to alleviate inflammatory conditions in mice without hepatotoxicity. We show that oral treatment with sterol-based LXR agonists in mice significantly reduces dextran sulfate sodium colitis-induced body weight loss, which is accompanied by reduced expression of inflammatory markers in the large intestine. The anti-inflammatory property of these agonists is recapitulated in vitro in mouse lamina propria mononuclear cells, human colonic epithelial cells, and human peripheral blood mononuclear cells. In addition, treatment with LXR agonists dramatically suppresses inflammatory cytokine expression in a model of traumatic brain injury. Importantly, in both disease models, the sterol-based agonists do not affect the liver, and the conventional agonist T0901317 results in significant liver lipid accumulation and injury. Overall, these results provide evidence for the development of sterol-based LXR agonists as novel therapeutics for chronic inflammatory diseases.-Yu, S., Li, S., Henke, A., Muse, E. D., Cheng, B., Welzel, G., Chatterjee, A. K., Wang, D., Roland, J., Glass, C. K., Tremblay, M. Dissociated sterol-based liver X receptor agonists as therapeutics for chronic inflammatory diseases. PMID:27025962

  17. The Central Role of the Gut Microbiota in Chronic Inflammatory Diseases

    PubMed Central

    Ferreira, Caroline Marcantonio; Vieira, Angélica Thomaz; Vinolo, Marco Aurelio Ramirez; Oliveira, Fernando A.; Curi, Rui; Martins, Flaviano dos Santos

    2014-01-01

    The commensal microbiota is in constant interaction with the immune system, teaching immune cells to respond to antigens. Studies in mice have demonstrated that manipulation of the intestinal microbiota alters host immune cell homeostasis. Additionally, metagenomic-sequencing analysis has revealed alterations in intestinal microbiota in patients suffering from inflammatory bowel disease, asthma, and obesity. Perturbations in the microbiota composition result in a deficient immune response and impaired tolerance to commensal microorganisms. Due to altered microbiota composition which is associated to some inflammatory diseases, several strategies, such as the administration of probiotics, diet, and antibiotic usage, have been utilized to prevent or ameliorate chronic inflammatory diseases. The purpose of this review is to present and discuss recent evidence showing that the gut microbiota controls immune system function and onset, development, and resolution of some common inflammatory diseases. PMID:25309932

  18. Acne: a new model of immune-mediated chronic inflammatory skin disease.

    PubMed

    Antiga, E; Verdelli, A; Bonciani, D; Bonciolini, V; Caproni, M; Fabbri, P

    2015-04-01

    Acne is a chronic inflammatory disease of the sebaceous-pilosebaceous unit. Interestingly, inflammation can be detected by histopathological examination and immuohistochemical analysis even in the apparently non-inflammatory acneic lesions, such as comedones. In the last years, it has been clearly demonstrated that acne development is linked to the combination of predisposing genetic factors and environmental triggers, among which a prominent role is played by the follicular colonization by Propionibacterium acnes (P. acnes). P. acnes displays several activities able to promote the development of acne skin lesions, including the promotion of follicular hyperkeratinisation, the induction of sebogenesis, and the stimulation of an inflammatory response by the secretion of proinflammatory molecules and by the activation of innate immunity, that is followed by a P. acnes-specific adaptive immune response. In addition, P. acnes-independent inflammation mediated by androgens or by a neurogenic activation, followed by the secretion in the skin of pro-inflammatory neuropeptides, can occur in acne lesions. In conclusion, acne can be considered as a model of immune-mediated chronic inflammatory skin disease, characterized by an innate immune response that is not able to control P. acnes followed by a Th1-mediated adaptive immune response, that becomes self-maintaining independently from P. acnes itself. PMID:25876146

  19. Novel Roles for Chloride Channels, Exchangers, and Regulators in Chronic Inflammatory Airway Diseases

    PubMed Central

    Sala-Rabanal, Monica; Yurtsever, Zeynep; Berry, Kayla N.; Brett, Tom J.

    2015-01-01

    Chloride transport proteins play critical roles in inflammatory airway diseases, contributing to the detrimental aspects of mucus overproduction, mucus secretion, and airway constriction. However, they also play crucial roles in contributing to the innate immune properties of mucus and mucociliary clearance. In this review, we focus on the emerging novel roles for a chloride channel regulator (CLCA1), a calcium-activated chloride channel (TMEM16A), and two chloride exchangers (SLC26A4/pendrin and SLC26A9) in chronic inflammatory airway diseases. PMID:26612971

  20. Dietary resistant starch and chronic inflammatory bowel diseases.

    PubMed

    Jacobasch, G; Schmiedl, D; Kruschewski, M; Schmehl, K

    1999-11-01

    These studies were performed to test the benefit of resistant starch on ulcerative colitis via prebiotic and butyrate effects. Butyrate, propionate, and acetate are produced in the colon of mammals as a result of microbial fermentation of resistant starch and other dietary fibers. Butyrate plays an important role in the colonic mucosal growth and epithelial proliferation. A reduction in the colonic butyrate level induces chronic mucosal atrophy. Short-chain fatty acid enemas increase mucosal generation, crypt length, and DNA content of the colonocytes. They also ameliorate symptoms of ulcerative colitis in human patients and rats injected with trinitrobenzene sulfonic acid (TNBS). Butyrate, and also to a lesser degree propionate, are substrates for the aerobic energy metabolism, and trophic factors of the colonocytes. Adverse butyrate effects occur in normal and neoplastic colonic cells. In normal cells, butyrate induces proliferation at the crypt base, while inhibiting proliferation at the crypt surface. In neoplastic cells, butyrate inhibits DNA synthesis and arrests cell growth in the G1 phase of the cell cycle. The improvement of the TNBS-induced colonic inflammation occurred earlier in the resistant starch (RS)-fed rats than in the RS-free group. This benefit coincided with activation of colonic epithelial cell proliferation and the subsequent restoration of apoptosis. The noncollagenous basement membrane protein laminin was regenerated initially in the RS-fed group, demonstrating what could be a considered lower damage to the intestinal barrier function. The calculation of intestinal short-chain fatty acid absorption confirmed this conclusion. The uptake of short-chain fatty acids in the colon is strongly inhibited in the RS-free group, but only slightly reduced in the animals fed with RS. Additionally, RS enhanced the growth of intestinal bacteria assumed to promote health. Further studies involving patients suffering from ulcerative colitis are necessary to

  1. Chronic Inflammatory Liver Disease in Mice Expressing a CD28-specific Ligand

    PubMed Central

    Corse, Emily; Gottschalk, Rachel A.; Park, Joon Seok; Sepulveda, Manuel A.; Loke, P’ng; Sullivan, Timothy J.; Johnson, Linda K.; Allison, James P.

    2012-01-01

    Inflammation of the normally tolerant liver microenvironment precedes development of chronic liver disease. Study of the pathogenesis of autoimmune liver diseases such as autoimmune hepatitis (AIH) has been hampered by a lack of autochthonous chronic animal models. Through our studies of T cell costimulation, we generated transgenic mice expressing a ligand specific for the CD28 receptor, which normally shares ligands with the related inhibitory receptor CTLA-4. The mice spontaneously develop chronic inflammatory liver disease with several pathologies found in AIH including elevated serum aminotransferases in the context of normal alkaline phosphatase and bilirubin levels, lymphocytic inflammation, focal necrosis, oval cell hyperplasia, and fibrosis. The prevalence of IFN-γ-producing CD8+ T cells in the livers of transgenic mice suggests a role for autoimmune cytotoxicity in the chronic disease state. The CD28 ligand-specific transgenic mice will facilitate evaluation of CD8+ T cell function in liver disease pathologies found in AIH. PMID:23248264

  2. Anti-inflammatory effects of chronic aspirin on brain arachidonic acid metabolites.

    PubMed

    Basselin, Mireille; Ramadan, Epolia; Chen, Mei; Rapoport, Stanley I

    2011-01-01

    Pro-inflammatory and anti-inflammatory mediators derived from arachidonic acid (AA) modulate peripheral inflammation and its resolution. Aspirin (ASA) is a unique non-steroidal anti-inflammatory drug, which switches AA metabolism from prostaglandin E₂ (PGE₂) and thromboxane B₂ (TXB₂) to lipoxin A₄ (LXA₄) and 15-epi-LXA₄. However, it is unknown whether chronic therapeutic doses of ASA are anti-inflammatory in the brain. We hypothesized that ASA would dampen increases in brain concentrations of AA metabolites in a rat model of neuroinflammation, produced by a 6-day intracerebroventricular infusion of bacterial lipopolysaccharide (LPS). In rats infused with LPS (0.5 ng/h) and given ASA-free water to drink, concentrations in high-energy microwaved brain of PGE₂, TXB₂ and leukotriene B₄ (LTB₄) were elevated. In rats infused with artificial cerebrospinal fluid, 6 weeks of treatment with a low (10 mg/kg/day) or high (100 mg/kg/day) ASA dose in drinking water decreased brain PGE₂, but increased LTB₄, LXA₄ and 15-epi-LXA₄ concentrations. Both doses attenuated the LPS effects on PGE₂, and TXB₂. The increments in LXA₄ and 15-epi-LXA₄ caused by high-dose ASA were significantly greater in LPS-infused rats. The ability of ASA to increase anti-inflammatory LXA₄ and 15-epi-LXA₄ and reduce pro-inflammatory PGE₂ and TXB₂ suggests considering aspirin further for treating clinical neuroinflammation. PMID:20981485

  3. Targeted anti-inflammatory therapeutics in asthma and chronic obstructive lung disease

    PubMed Central

    Durham, Andrew L.; Caramori, Gaetano; Chung, Kian F.; Adcock, Ian M.

    2016-01-01

    Asthma and chronic obstructive pulmonary disease (COPD) are chronic inflammatory diseases of the airway, although the drivers and site of the inflammation differ between diseases. Asthmatics with a neutrophilic airway inflammation are associated with a poor response to corticosteroids, whereas asthmatics with eosinophilic inflammation respond better to corticosteroids. Biologicals targeting the Th2-eosinophil nexus such as anti–interleukin (IL)-4, anti–IL-5, and anti–IL-13 are ineffective in asthma as a whole but are more effective if patients are selected using cellular (eg, eosinophils) or molecular (eg, periostin) biomarkers. This highlights the key role of individual inflammatory mediators in driving the inflammatory response and for accurate disease phenotyping to allow greater understanding of disease and development of patient-oriented antiasthma therapies. In contrast to asthmatic patients, corticosteroids are relatively ineffective in COPD patients. Despite stratification of COPD patients, the results of targeted therapy have proved disappointing with the exception of recent studies using CXC chemokine receptor (CXCR)2 antagonists. Currently, several other novel mediator-targeted drugs are undergoing clinical trials. As with asthma specifically targeted treatments may be of most benefit in specific COPD patient endotypes. The use of novel inflammatory mediator-targeted therapeutic agents in selected patients with asthma or COPD and the detection of markers of responsiveness or nonresponsiveness will allow a link between clinical phenotypes and pathophysiological mechanisms to be delineated reaching the goal of endotyping patients. PMID:26334389

  4. Targeted anti-inflammatory therapeutics in asthma and chronic obstructive lung disease.

    PubMed

    Durham, Andrew L; Caramori, Gaetano; Chung, Kian F; Adcock, Ian M

    2016-01-01

    Asthma and chronic obstructive pulmonary disease (COPD) are chronic inflammatory diseases of the airway, although the drivers and site of the inflammation differ between diseases. Asthmatics with a neutrophilic airway inflammation are associated with a poor response to corticosteroids, whereas asthmatics with eosinophilic inflammation respond better to corticosteroids. Biologicals targeting the Th2-eosinophil nexus such as anti-interleukin (IL)-4, anti-IL-5, and anti-IL-13 are ineffective in asthma as a whole but are more effective if patients are selected using cellular (eg, eosinophils) or molecular (eg, periostin) biomarkers. This highlights the key role of individual inflammatory mediators in driving the inflammatory response and for accurate disease phenotyping to allow greater understanding of disease and development of patient-oriented antiasthma therapies. In contrast to asthmatic patients, corticosteroids are relatively ineffective in COPD patients. Despite stratification of COPD patients, the results of targeted therapy have proved disappointing with the exception of recent studies using CXC chemokine receptor (CXCR)2 antagonists. Currently, several other novel mediator-targeted drugs are undergoing clinical trials. As with asthma specifically targeted treatments may be of most benefit in specific COPD patient endotypes. The use of novel inflammatory mediator-targeted therapeutic agents in selected patients with asthma or COPD and the detection of markers of responsiveness or nonresponsiveness will allow a link between clinical phenotypes and pathophysiological mechanisms to be delineated reaching the goal of endotyping patients. PMID:26334389

  5. IL-32: A Novel Pluripotent Inflammatory Interleukin, towards Gastric Inflammation, Gastric Cancer, and Chronic Rhino Sinusitis

    PubMed Central

    2016-01-01

    A vast variety of nonstructural proteins have been studied for their key roles and involvement in a number of biological phenomenona. Interleukin-32 is a novel cytokine whose presence has been confirmed in most of the mammals except rodents. The IL-32 gene was identified on human chromosome 16 p13.3. The gene has eight exons and nine splice variants, namely, IL-32α, IL-32β, IL-32γ, IL-32δ, IL-32ε, IL-32ζ, IL-32η, IL-32θ, and IL-32s. It was found to induce the expression of various inflammatory cytokines including TNF-α, IL-6, and IL-1β as well as macrophage inflammatory protein-2 (MIP-2) and has been reported previously to be involved in the pathogenesis and progression of a number of inflammatory disorders, namely, inflammatory bowel disease (IBD), gastric inflammation and cancer, rheumatoid arthritis, and chronic obstructive pulmonary disease (COPD). In the current review, we have highlighted the involvement of IL-32 in gastric cancer, gastric inflammation, and chronic rhinosinusitis. We have also tried to explore various mechanisms suspected to induce the expression of this extraordinary cytokine as well as various mechanisms of action employed by IL-32 during the mediation and progression of the above said problems. PMID:27143819

  6. Pericarditis and chronic inflammatory demyelinating polyneuropathy during therapy with pegylated interferon alfa-2a for chronic hepatitis C.

    PubMed

    Nishio, Kazuaki; Konndo, Takeshi; Okada, Shunichi; Enchi, Machiko

    2010-09-27

    We report a case of pericarditis and chronic inflammatory demyelinating polyneuropathy with biological signs of a lupus-like syndrome due to pegylated interferon alfa-2a therapy during treatment for chronic hepatitis C. The patient developed moderate weakness in the lower limbs and dyspnea. He was hospitalized for congestive heart failure. An electrocardiogram showed gradual ST-segment elevation in leads V(1) through V(6) without coronary artery disease. A transthoracic cardiac ultrasonographic study revealed moderate pericardial effusion with normal left ventricular function. Anti-DNA antibody and antids DNA IgM were positive. Neurological examination revealed a symmetrical predominantly sensory polyneuropathy with impairment of light touch and pin prick in globe and stoking-like distribution. Treatment with prednisolone improved the pericarditis and motor nerve disturbance and the treatment with intravenous immunoglobulin improved the sensory nerve disturbance. PMID:21161021

  7. Pericarditis and chronic inflammatory demyelinating polyneuropathy during therapy with pegylated interferon alfa-2a for chronic hepatitis C

    PubMed Central

    Nishio, Kazuaki; Konndo, Takeshi; Okada, Shunichi; Enchi, Machiko

    2010-01-01

    We report a case of pericarditis and chronic inflammatory demyelinating polyneuropathy with biological signs of a lupus-like syndrome due to pegylated interferon alfa-2a therapy during treatment for chronic hepatitis C. The patient developed moderate weakness in the lower limbs and dyspnea. He was hospitalized for congestive heart failure. An electrocardiogram showed gradual ST-segment elevation in leads V1 through V6 without coronary artery disease. A transthoracic cardiac ultrasonographic study revealed moderate pericardial effusion with normal left ventricular function. Anti-DNA antibody and antids DNA IgM were positive. Neurological examination revealed a symmetrical predominantly sensory polyneuropathy with impairment of light touch and pin prick in globe and stoking-like distribution. Treatment with prednisolone improved the pericarditis and motor nerve disturbance and the treatment with intravenous immunoglobulin improved the sensory nerve disturbance. PMID:21161021

  8. The Role of Inflammatory Pathways in Implantation Failure: Chronic Endometritis and Hydrosalpinges.

    PubMed

    Akopians, Alin L; Pisarska, Margareta D; Wang, Erica T

    2015-07-01

    The process of implantation is highly complex and involves a delicate interplay between the embryo and the appropriate maternal environment. The failure to implant is thought to be due to maternal factors or embryonic factors. Inflammation can be a part of the normal physiologic process during implantation; however, there are also pathologic entities that adversely affect uterine receptivity. This review will focus on chronic endometritis and hydrosalpinges as two specific inflammatory processes that contribute to implantation failure. For both chronic endometritis and hydrosalpinges, we will review the diagnosis, pathophysiology, and effect on implantation following treatment. The existing literature conclusively demonstrates that hydrosalpinges should be addressed by either laparoscopic salpingectomy or proximal tubal occlusion prior to in vitro fertilization. The picture for chronic endometritis is less clear since the diagnosis and treatment of chronic endometritis are not standardized, and there are no available randomized controlled trials on this topic. Future studies may target gene expression arrays as a method for further elucidating the role of inflammatory markers in normal and abnormal implantation processes. PMID:26132934

  9. Association of anemia and erythropoiesis stimulating agents with inflammatory biomarkers in chronic kidney disease.

    PubMed

    Keithi-Reddy, Sai Ram; Addabbo, Francesco; Patel, Tejas V; Mittal, Bharati V; Goligorsky, Michael S; Singh, Ajay K

    2008-09-01

    Inflammatory cytokines are important predictors of cardiovascular mortality especially in patients with chronic kidney disease. Here we explored the relationship of anemia and epoetin treatment to inflammatory cytokine levels in patients with chronic kidney disease. One hundred non-dialysis patients with chronic kidney disease over 18 years of age were evenly split into anemic and non-anemic cohorts. Of the 50 anemic patients, 23 were receiving erythropoiesis stimulating agents treatments. Levels of tumor necrosis factor (TNF)-alpha were found to be significantly higher and serum albumin was significantly lower with trends towards higher interleukin (IL)-6 and IL-8 in anemic compared to non-anemic patients. Further analysis by multiple logistic regression found that anemic patients treated with erythropoiesis stimulating agents had significantly higher odds for the upper two quartiles for IL-6, IL-8 and TNF-alpha compared to non-anemic patients. Our study found that the anemia of chronic kidney disease was associated with up regulation of TNF-alpha, and possibly IL-6 and IL-8 along with increased levels of these proinflammatory cytokines in patients treated with epoetin. PMID:18547996

  10. Chronic inflammatory airway diseases: the central role of the epithelium revisited.

    PubMed

    Gohy, S T; Hupin, C; Pilette, C; Ladjemi, M Z

    2016-04-01

    The respiratory epithelium plays a critical role for the maintenance of airway integrity and defense against inhaled particles. Physical barrier provided by apical junctions and mucociliary clearance clears inhaled pathogens, allergens or toxics, to prevent continuous stimulation of adaptive immune responses. The "chemical barrier", consisting of several anti-microbial factors such as lysozyme and lactoferrin, constitutes another protective mechanism of the mucosae against external aggressions before adaptive immune response starts. The reconstruction of damaged respiratory epithelium is crucial to restore this barrier. This review examines the role of the airway epithelium through recent advances in health and chronic inflammatory diseases in the lower conducting airways (in asthma and chronic obstructive pulmonary disease). Better understanding of normal and altered epithelial functions continuously provides new insights into the physiopathology of chronic airway diseases and should help to identify new epithelial-targeted therapies. PMID:27021118

  11. Control of Inflammatory Responses: a New Paradigm for the Treatment of Chronic Neuronal Diseases.

    PubMed

    Woo, Joo Hong; Lee, Jee Hoon; Kim, Hyunmi; Park, Soo Jung; Joe, Eun-Hye; Jou, Ilo

    2015-06-01

    The term 'inflammation' was first introduced by Celsus almost 2000 years ago. Biological and medical researchers have shown increasing interest in inflammation over the past few decades, in part due to the emerging burden of chronic and degenerative diseases resulting from the increased longevity that has arisen thanks to modern medicine. Inflammation is believed to play critical roles in the pathogenesis of degenerative brain diseases, including Alzheimer's disease and Parkinson's disease. Accordingly, researchers have sought to combat such diseases by controlling inflammatory responses. In this review, we describe the endogenous inflammatory stimulators and signaling pathways in the brain. In particular, our group has focused on the JAK-STAT pathway, identifying anti-inflammatory targets and testing the effects of various anti-inflammatory drugs. This work has shown that the JAK-STAT pathway and its downstream are negatively regulated by phosphatases (SHP2 and MKP-1), inhibitory proteins (SOCS1 and SOCS3) and a nuclear receptor (LXR). These negative regulators are controlled at various levels (e.g. transcriptional, post-transcriptional and post-translational). Future study of these proteins could facilitate the manipulation of the inflammatory response, which plays ubiquitous, diverse and ambivalent roles under physiological and pathological conditions. PMID:26113788

  12. Periodontitis and Periodontal Disease - Innovative Strategies for Reversing the Chronic Infectious and Inflammatory Condition by Natural Products.

    PubMed

    Lazar, Veronica; Saviuc, Crina-Maria; Chifiriuc, Mariana Carmen

    2016-01-01

    Oral microbiota of the mouth is the most diverse microbial community in the human body and plays a decisive role in the emergence and evolution of gingival pathology, contributing as well to the host general health condition, based on complex interactions established between the microbial community members and the host. A specific shift in the quantity and diversity of the microbial community developed on dental and mucosal surfaces, could lead to the occurrence of chronic inflammation mediated by the overproduction of pro-inflammatory cytokines. The mechanical treatment and current medication efficiency for the periodontal disease is limited in time due to the rapid plaque forming. Also, the antimicrobial treatment is limited by the sessile growth of the microorganisms, resulting in a poor biofilm penetration by biocides or antibiotics. In line with that, the attention of the scientific community shifted to ethnopharmacology as a complementary, or alternative therapeutic option for fighting infections with resistant bacteria. The vegetal and bee products are an important source of bioactive compounds, acting as harmless antimicrobials and periodontal inflammation suppressors. Vegetable bioproducts have been proven to exhibit multiple antipathogenic effects, such as microbicidal activity, virulence attenuation, and synergistic effects between the components found in the complex vegetal matrixes, or with conventional biocides, as well as immunomodulatory effects. The purpose of this review is to highlight the importance of vegetable products as a possible complementary treatment for periodontitis and their potential for the development of innovative therapeutic strategies. PMID:26561076

  13. The immune protective effect of the Mediterranean diet against chronic low-grade inflammatory diseases.

    PubMed

    Casas, Rosa; Sacanella, Emilio; Estruch, Ramon

    2014-01-01

    Dietary patterns high in refined starches, sugar, and saturated and trans-fatty acids, poor in natural antioxidants and fiber from fruits, vegetables, and whole grains, and poor in omega-3 fatty acids may cause an activation of the innate immune system, most likely by excessive production of proinflammatory cytokines associated with a reduced production of anti-inflammatory cytokines. The Mediterranean Diet (MedDiet) is a nutritional model inspired by the traditional dietary pattern of some of the countries of the Mediterranean basin. This dietary pattern is characterized by the abundant consumption of olive oil, high consumption of plant foods (fruits, vegetables, pulses, cereals, nuts and seeds); frequent and moderate intake of wine (mainly with meals); moderate consumption of fish, seafood, yogurt, cheese, poultry and eggs; and low consumption of red meat, processed meat products and seeds. Several epidemiological studies have evaluated the effects of a Mediterranean pattern as protective against several diseases associated with chronic low-grade inflammation such as cancer, diabetes, obesity, atherosclerosis, metabolic syndrome and cognition disorders. The adoption of this dietary pattern could counter the effects of several inflammatory markers, decreasing, for example, the secretion of circulating and cellular biomarkers involved in the atherosclerotic process. Thus, the aim of this review was to consider the current evidence about the effectiveness of the MedDiet in these chronic inflammatory diseases due to its antioxidant and anti-inflammatory properties, which may not only act on classical risk factors but also on inflammatory biomarkers such as adhesion molecules, cytokines or molecules related to the stability of atheromatic plaque. PMID:25244229

  14. The Immune Protective Effect of the Mediterranean Diet against Chronic Low-grade Inflammatory Diseases

    PubMed Central

    Casas, Rosa; Sacanella, Emilio; Estruch, Ramon

    2014-01-01

    Dietary patterns high in refined starches, sugar, and saturated and trans-fatty acids, poor in natural antioxidants and fiber from fruits, vegetables, and whole grains, and poor in omega-3 fatty acids may cause an activation of the innate immune system, most likely by excessive production of proinflammatory cytokines associated with a reduced production of anti-inflammatory cytokines. The Mediterranean Diet (MedDiet) is a nutritional model inspired by the traditional dietary pattern of some of the countries of the Mediterranean basin. This dietary pattern is characterized by the abundant consumption of olive oil, high consumption of plant foods (fruits, vegetables, pulses, cereals, nuts and seeds); frequent and moderate intake of wine (mainly with meals); moderate consumption of fish, seafood, yogurt, cheese, poultry and eggs; and low consumption of red meat, processed meat products and seeds. Several epidemiological studies have evaluated the effects of a Mediterranean pattern as protective against several diseases associated with chronic low-grade inflammation such as cancer, diabetes, obesity, atherosclerosis, metabolic syndrome and cognition disorders. The adoption of this dietary pattern could counter the effects of several inflammatory markers, decreasing, for example, the secretion of circulating and cellular biomarkers involved in the atherosclerotic process. Thus, the aim of this review was to consider the current evidence about the effectiveness of the MedDiet in these chronic inflammatory diseases due to its antioxidant and anti-inflammatory properties, which may not only act on classical risk factors but also on inflammatory biomarkers such as adhesion molecules, cytokines or molecules related to the stability of atheromatic plaque. PMID:25244229

  15. Sleep Loss and the Inflammatory Response in Mice Under Chronic Environmental Circadian Disruption

    PubMed Central

    Castanon-Cervantes, Oscar; Natarajan, Divya; Delisser, Patrick; Davidson, Alec J.; Paul, Ketema N.

    2013-01-01

    Shift work and trans-time zone travel lead to insufficient sleep and numerous pathologies. Here, we examined sleep/wake dynamics during chronic exposure to environmental circadian disruption (ECD), and if chronic partial sleep loss associated with ECD influences the induction of shift-related inflammatory disorder. Sleep and wakefulness were telemetrically recorded across three months of ECD, in which the dark-phase of a light-dark cycle was advanced weekly by 6 h. A three month regimen of ECD caused a temporary reorganization of sleep (NREM and REM) and wake processes across each week, resulting in an approximately 10% net loss of sleep each week relative to baseline levels. A separate group of mice were subjected to ECD or a regimen of imposed wakefulness (IW) aimed to mimic sleep amounts under ECD for one month. Fos-immunoreactivity (IR) was quantified in sleep-wake regulatory areas: the nucleus accumbens (NAc), basal forebrain (BF), and medial preoptic area (MnPO). To assess the inflammatory response, trunk blood was treated with lipopolysaccharide (LPS) and subsequent release of IL-6 was measured. Fos-IR was greatest in the NAc, BF, and MnPO of mice subjected to IW. The inflammatory response to LPS was elevated in mice subjected to ECD, but not mice subjected to IW. Thus, the net sleep loss that occurs under ECD is not associated with a pathological immune response. PMID:23696854

  16. Sleep loss and the inflammatory response in mice under chronic environmental circadian disruption.

    PubMed

    Brager, Allison J; Ehlen, J Christopher; Castanon-Cervantes, Oscar; Natarajan, Divya; Delisser, Patrick; Davidson, Alec J; Paul, Ketema N

    2013-01-01

    Shift work and trans-time zone travel lead to insufficient sleep and numerous pathologies. Here, we examined sleep/wake dynamics during chronic exposure to environmental circadian disruption (ECD), and if chronic partial sleep loss associated with ECD influences the induction of shift-related inflammatory disorder. Sleep and wakefulness were telemetrically recorded across three months of ECD, in which the dark-phase of a light-dark cycle was advanced weekly by 6 h. A three month regimen of ECD caused a temporary reorganization of sleep (NREM and REM) and wake processes across each week, resulting in an approximately 10% net loss of sleep each week relative to baseline levels. A separate group of mice were subjected to ECD or a regimen of imposed wakefulness (IW) aimed to mimic sleep amounts under ECD for one month. Fos-immunoreactivity (IR) was quantified in sleep-wake regulatory areas: the nucleus accumbens (NAc), basal forebrain (BF), and medial preoptic area (MnPO). To assess the inflammatory response, trunk blood was treated with lipopolysaccharide (LPS) and subsequent release of IL-6 was measured. Fos-IR was greatest in the NAc, BF, and MnPO of mice subjected to IW. The inflammatory response to LPS was elevated in mice subjected to ECD, but not mice subjected to IW. Thus, the net sleep loss that occurs under ECD is not associated with a pathological immune response. PMID:23696854

  17. Inflammatory reaction in chronic periodontopathies in patients with diabetes mellitus. Histological and immunohistochemical study.

    PubMed

    Camen, Georgiana Cristiana; Caraivan, O; Olteanu, Mădălina; Camen, A; Bunget, Adina; Popescu, Florina Carmen; Predescu, Anca

    2012-01-01

    Chronic periodontopathies and diabetes mellitus are two clinical entities, which reciprocally condition one another. The periodontal disease is considered a major complication, which induces an unfavorable evolution of diabetes mellitus. Diabetes mellitus is an endocrine disease which favors the occurrence of periodontopathy through gum's microvascular disorders, the selection and development of an aggressive bacterial plaque and through an exaggerate inflammatory response to the microflora within the oral cavity. Both diabetes mellitus and periodontal disease have an increasing incidence in the whole world. Development of periodontopathy is related to the aggression of bacterial flora in dental plaque, flora that is influenced on its turn by the evolution of diabetes mellitus. In our study, we have evaluated the inflammatory reaction in periodontium in patients with slowly and progressive periodontitis in patients with diabetes mellitus who had diabetes longer than five years. It has been found that all patients presented a chronic inflammatory infiltrate, abundant, with round mononuclear cells of lymphocyte, plasma cells and macrophage type, with non-homogenous arrangement, more intensely where the covering epithelium presented erosions or necrotic areas. Out of the immunity system cells, the most numerous where of T-lymphocytes type. PMID:22395500

  18. Anti-inflammatory effects of chronic aspirin on brain arachidonic acid metabolites

    PubMed Central

    Basselin, Mireille; Ramadan, Epolia; Chen, Mei; Rapoport, Stanley I.

    2010-01-01

    Pro-inflammatory and anti-inflammatory mediators derived from arachidonic acid (AA) modulate peripheral inflammation and its resolution. Aspirin (ASA) is a unique non-steroidal anti-inflammatory drug, which switches AA metabolism from prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) to lipoxin A4 (LXA4) and 15-epi-LXA4. However it is unknown whether chronic therapeutic doses of ASA are anti-inflammatory in the brain. We hypothesized that ASA would dampen increases in brain concentrations of AA metabolites in a rat model of neuroinflammation, produced by a 6-day intracerebroventricular infusion of bacterial lipopolysaccharide (LPS). In rats infused with LPS (0.5 ng/h) and given ASA-free water to drink, concentrations in high-energy microwaved brain of PGE2, TXB2 and leukotriene B4 (LTB4) were elevated. In rats infused with artificial cerebrospinal fluid, 6 weeks of treatment with a low (10 mg/kg/day) or high (100 mg/kg/day) ASA dose in drinking water decreased brain PGE2, but increased LTB4, LXA4 and 15-epi-LXA4 concentrations. Both doses attenuated the LPS effects on PGE2, and TXB2. The increments in LXA4 and 15-epi-LXA4 caused by high-dose ASA were significantly greater in LPS-infused rats. The ability of ASA to increase anti-inflammatory LXA4 and 15-epi-LXA4 and reduce pro-inflammatory PGE2 and TXB2 suggests considering aspirin further for treating clinical neuroinflammation. PMID:20981485

  19. Doxycycline Promotes Carcinogenesis & Metastasis via Chronic Inflammatory Pathway: An In Vivo Approach

    PubMed Central

    Nanda, Neha; Dhawan, Devinder K.; Bhatia, Alka; Mahmood, Akhtar; Mahmood, Safrun

    2016-01-01

    Background Doxycycline (DOX) exhibits anti-inflammatory, anti-tumor, and pro-apoptotic activity and is being tested in clinical trials as a chemotherapeutic agent for several cancers, including colon cancer. Materials & Methods In the current study, the chemotherapeutic activity of doxycycline was tested in a rat model of colon carcinogenesis, induced by colon specific cancer promoter, 1,2, dimethylhydrazine (DMH) as well as study the effect of DOX-alone on a separate group of rats. Results Doxycycline administration in DMH-treated rats (DMH-DOX) unexpectedly increased tumor multiplicity, stimulated progression of colonic tumor growth from adenomas to carcinomas and revealed metastasis in small intestine as determined by macroscopic and histopathological analysis. DOX-alone treatment showed markedly enhanced chronic inflammation and reactive hyperplasia, which was dependent upon the dose of doxycycline administered. Moreover, immunohistochemical analysis revealed evidence of inflammation and anti-apoptotic action of DOX by deregulation of various biomarkers. Conclusion These results suggest that doxycycline caused chronic inflammation in colon, small intestine injury, enhanced the efficacy of DMH in tumor progression and provided a mechanistic link between doxycycline-induced chronic inflammation and tumorigenesis. Ongoing studies thus may need to focus on the molecular mechanisms of doxycycline action, which lead to its inflammatory and tumorigenic effects. PMID:26998758

  20. Wegener’s granulomatosis mimicking inflammatory bowel disease and presenting with chronic enteritis

    PubMed Central

    Shahedi, Kamyar; Hanna, Ramy Magdy; Melamed, Oleg; Wilson, James

    2013-01-01

    Wegener’s granulomatosis, also known as anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, is a small vessel vasculitis with primarily pulmonary, renal, and sinus disease manifestations. The prevalence of Wegener’s granulomatosis is three cases per 100,000 patients. Cardiovascular, neurologic, cutaneous, and joint manifestations have been reported in many case reports and case series. Gastrointestinal manifestations are less noted in Wegener’s granulomatosis, although they have been previously reported in the form of intestinal perforation and intestinal ischemia. Additionally, there are characteristic findings of vasculitis that are noted with active Wegener’s granulomatosis of the small bowel. We report a case of an elderly patient who presented with weight loss, diarrhea, and hematochezia. His symptoms were chronic and had lasted for more than 1 year before diagnosis. Inflammatory bowel disease or chronic enteritis due to Salmonella arizonae because of reptile exposure originally were suspected as etiologies of his presentation. The findings of proteinuria, renal failure, and pauci-immune glomerulonephritis on renal biopsy, in conjunction with an elevated c-ANCA titer, confirmed the diagnosis of Wegener’s granulomatosis with associated intestinal vasculitis. This case demonstrates an atypical presentation of chronic duodenitis and jejunitis secondary to Wegener’s granulomatosis, which mimicked inflammatory bowel disease. PMID:24124396

  1. Mutual Interaction of Basophils and T Cells in Chronic Inflammatory Diseases

    PubMed Central

    Sarfati, Marika; Wakahara, Keiko; Chapuy, Laurence; Delespesse, Guy

    2015-01-01

    Basophils are, together with mast cells, typical innate effector cells of allergen-induced IgE-dependent allergic diseases. Both cell types express the high-affinity receptor for IgE (FcεR1), release histamine, inflammatory mediators, and cytokines following FcεR1 cross-linking. Basophils are rare granulocytes in blood, lymphoid, and non-lymphoid tissues, and the difficulties to detect and isolate these cells has hampered the study of their biology and the understanding of their possible role in pathology. Furthermore, the existence of other FcεR1-expressing cells, including professional Ag-presenting dendritic cells, generated some controversy regarding the ability of basophils to express MHC Class II molecules, present Ag and drive naïve T cell differentiation into Th2 cells. The focus of this review is to present the recent advances on the interactions between basophils and peripheral blood and tissue memory Th1, Th2, and Th17 cells, as well as their potential role in IgE-independent non-allergic chronic inflammatory disorders, including human inflammatory bowel diseases. Basophils interactions with the innate players of IgE-dependent allergic inflammation, particularly innate lymphoid cells, will also be considered. The previously unrecognized function for basophils in skewing adaptive immune responses opens novel perspectives for the understanding of their contribution to the pathogenesis of inflammatory diseases. PMID:26284078

  2. [Definition of inflammatory subtypes of chronic rhinosinusitis with nasal polyp and asthma].

    PubMed

    Wu, Dawei; Zhang, Min; Song, Qian

    2015-08-01

    Chronic rhinosinusitis with nasal polyps (CRSwNP) and asthma is a common clinical refractory airway disease. Comprehensive treatment of nasal endoscopic surgery including nasal endoscopic surgery and medication, which can significantly improve nose-pulmonary symptoms and make sinusitis and asthma easier to be controlled by medication, has certain superiority. But the existence of disease heterogeneity of CRSwNP with asthma causes different reactions to the current treatment, which manifests as parts of polyps and asthma easy to recur and difficult to control. According to the research recently, the study of the heterogeneity of airway diseases, for example endotype, is a hot area of research. Endotype is a subtype of a condition, which is defined by a distinct functional or pathobiological mechanism. This is distinct from a phenotype, which is any observable characteristic or trait of a disease. Different Inflammatory subtypes often represent different pathophysiology and even different pathogenesis. The concept of inflammatory subtypes of airway diseases provides a new perspective for studies of airway diseases of endotype and the mechanism of combined airway diseases. This review summarizes recent advances in the clinical characterization and treatment of the CRSwNP with asthma. On this basis, we analyze and summarize the heterogeneity of CRSwNP and asthma separately from the perspective of inflammatory subtypes. Then according to the concept of the combined airway diseases and the common pathogenesis, we put forward the definition of inflammatory subtypes of the CRSwNP with asthma and preliminarily discuss the method of the definition. PMID:26665469

  3. Management of Cardiovascular Risk in Patients with Chronic Inflammatory Diseases: Current Evidence and Future Perspectives.

    PubMed

    Lindhardsen, Jesper; Kristensen, Søren Lund; Ahlehoff, Ole

    2016-02-01

    An increased risk of cardiovascular disease (CVD) has been observed in a range of chronic inflammatory diseases (CID), including rheumatoid arthritis (RA), psoriasis, inflammatory bowel diseases (IBD), and systemic lupus erythematosus (SLE). The increased risk of CVDs and reduced life expectancy in these conditions has stimulated considerable research and started an ongoing discussion on the need for a multidisciplinary approach and dedicated guidelines on CVD prevention in these patients. In addition, the possibility of inhibiting inflammation as a means to preventing CVD in these patients has gained considerable interest in recent years. We briefly summarize the current level of evidence of the association between CIDs and CVD and cardiovascular risk management recommendations. Perspectives of ongoing and planned trials are discussed in consideration of potential ways to improve primary and secondary CVD prevention in patients with CID. PMID:26293235

  4. Angiogenesis in chronic hepatitis C is associated with inflammatory activity grade and fibrosis stage.

    PubMed

    Gabriel, Andrzej; Kukla, Michał; Wilk, Mariusz; Liszka, Łukasz; Petelenz, Michał; Musialik, Joanna

    2009-01-01

    Data regarding the assessment of angiogenesis in liver tissue in chronic hepatitis C (CHC) are rare. The study was performed to explain the association between the histopathological features and the number of new blood vessels in lobules and portal tracts in CHC. The second aim of the study was to define the localization of sprouting and pattern of formation of new vessels by estimating CD 34 antigen expression in the liver. The study involved 74 patients with CHC, infected with viral genotype 1b before antiviral therapy. The number of new-formatted blood vessels was positively associated with fibrosis stage and inflammatory activity grade in the liver biopsy from CHC patients. The relationship was evident in the portal tract, fibrous septa and periportal zones of lobules. The results suggest that inflammatory hepatocyte injury may promote neo-angiogenesis. PMID:19592175

  5. The involvement of the JAK-STAT signaling pathway in chronic inflammatory skin disease atopic dermatitis

    PubMed Central

    Bao, Lei; Zhang, Huayi; Chan, Lawrence S

    2013-01-01

    Atopic dermatitis (AD), a common chronic inflammatory skin disease, is characterized by inflammatory cell skin infiltration. The JAK-STAT pathway has been shown to play an essential role in the dysregulation of immune responses in AD, including the exaggeration of Th2 cell response, the activation of eosinophils, the maturation of B cells, and the suppression of regulatory T cells (Tregs). In addition, the JAK-STAT pathway, activated by IL-4, also plays a critical role in the pathogenesis of AD by upregulating epidermal chemokines, pro-inflammatroy cytokines, and pro-angiogenic factors as well as by downregulating antimicrobial peptides (AMPs) and factors responsible for skin barrier function. In this review, we will highlight the recent advances in our understanding of the JAK-STAT pathway in the pathogenesis of AD. PMID:24069552

  6. [Association of fatty acid metabolism with systemic inflammatory response in chronic respiratory diseases].

    PubMed

    Denisenko, Y K; Novgorodtseva, T P; Zhukova, N V; Antonuk, M V; Lobanova, E G; Kalinina, E P

    2016-03-01

    We examined composition of plasma non-esterified fatty acids (NFAs), erythrocyte fatty acids, levels of eicosanoids in patients with asthma and chronic obstructive pulmonary disease (COPD) with different type of the inflammatory response. The results of our study show that asthma and COPD in remission are associated with changes in the composition NFAs of plasma, FA of erythrocytes, level eicosanoid despite the difference in the regulation of immunological mechanisms of systemic inflammation. These changes are characterized by excessive production of arachidonic acid (20:4n-6) and cyclooxygenase and lipoxygenase metabolites (thromboxane B2, leukotriene B4) and deficiency of their functional antagonist, eicosapentaenoic acid (20:5n-3). The recognized association between altered fatty acid composition and disorders of the immune mechanisms of regulation of systemic inflammation in COPD and asthma demonstrated the important role of fatty acids and their metabolites in persistence of inflammatory processes in diseases of the respiratory system in the condition of remission. PMID:27420629

  7. Increased Anxiety-Like Behaviors in Rats Experiencing Chronic Inflammatory Pain

    PubMed Central

    Parent, Alexandre J.; Beaudet, Nicolas; Beaudry, Hélène; Bergeron, Jenny; Bérubé, Patrick; Drolet, Guy; Sarret, Philippe; Gendron, Louis

    2013-01-01

    For many patients, chronic pain is often accompanied, and sometimes amplified, by co-morbidities such as anxiety and depression. Although it represents important challenges, the establishment of appropriate preclinical behavioral models contributes to drug development for treating chronic inflammatory pain and associated psychopathologies. In this study, we investigated whether rats experiencing persistent inflammatory pain induced by intraplantar injection of complete Freund’s adjuvant (CFA) developed anxiety-like behaviors, and whether clinically used analgesic and anxiolytic drugs were able to reverse CFA-induced anxiety-related phenotypes. These behaviors were evaluated over 28 days in both CFA- and saline-treated groups with a variety of behavioral tests. CFA-induced mechanical allodynia resulted in increased anxiety-like behaviors as evidenced by: 1) a significant decrease in percentage of time spent and number of entries in open arms of the elevated-plus maze (EPM), 2) a decrease in number of central squares visited in the open field (OF), and 3) a reduction in active social interactions in the social interaction test (SI). The number of entries in closed arms in the EPM and the distance travelled in the OF used as indicators of locomotor performance did not differ between treatments. Our results also reveal that in CFA-treated rats, acute administration of morphine (3 mg/kg, s.c.) abolished tactile allodynia and anxiety-like behaviors, whereas acute administration of diazepam (1 mg/kg, s.c) solely reversed anxiety-like behaviors. Therefore, pharmacological treatment of anxiety-like behaviors induced by chronic inflammatory pain can be objectively evaluated using multiple behavioral tests. Such a model could help identify/validate alternative potential targets that influence pain and cognitive dimensions of anxiety. PMID:22245257

  8. Greater inflammatory activity and blunted glucocorticoid signaling in monocytes of chronically stressed caregivers

    PubMed Central

    Miller, Gregory E.; Murphy, Michael L.M.; Cashman, Rosemary; Ma, Roy; Ma, Jeffrey; Arevalo, Jesusa M.G.; Kobor, Michael S.; Cole, Steve W.

    2016-01-01

    Chronic stress is associated with morbidity and mortality from numerous conditions, many of whose pathogenesis involves persistent inflammation. Here, we examine how chronic stress influences signaling pathways that regulate inflammation in monocytes. The sample consisted of 33 adults caring for a family member with glioblastoma and 47 controls whose lives were free of major stressors. The subjects were assessed four times over eight months. Relative to controls, caregivers’ monocytes showed increased expression of genes bearing response elements for nuclear-factor kappa B, a key pro-inflammatory transcription factor. Simultaneously, caregivers showed reduced expression of genes with response elements for the glucocorticoid receptor, a transcription factor that conveys cortisol’s anti-inflammatory signals to monocytes. Transcript origin analyses revealed that CD14+/CD16− cells, a population of immature monocytes, were the predominate source of inflammatory gene expression among caregivers. We considered hormonal, molecular, and functional explanations for caregivers’ decreased glucocorticoid-mediated transcription. Across twelve days, the groups displayed similar diurnal cortisol profiles, suggesting that differential adrenocortical activity was not involved. Moreover, the groups’ monocytes expressed similar amounts of glucocorticoid receptor protein, suggesting that differential receptor availability was not involved. In ex vivo studies, subjects’ monocytes were stimulated with lipopolysaccharide, and caregivers showed greater production of the inflammatory cytokine interleukin-6 relative to controls. However, no group differences in functional glucocorticoid sensitivity were apparent; hydrocortisone was equally effective at inhibiting cytokine production in caregivers and controls. These findings may help shed light on the mechanisms through which caregiving increases vulnerability to inflammation-related diseases. PMID:25242587

  9. Multiorgan chronic inflammatory hepatobiliary pancreatic murine model deficient in tumor necrosis factor receptors 1 and 2

    PubMed Central

    Oz, Helieh S

    2016-01-01

    AIM: To provoke persistent/chronic multiorgan inflammatory response and to contribute to stones formation followed by fibrosis in hepatobiliary and pancreatic tissues. METHODS: Tumor necrosis factor receptors 1 and 2 (TNFR1/R2) deficient mice reared in-house were given dibutyltin dichloride (DBTC) twice within 10 d by oral gavage delivery. Sham control animals received vehicle treatment and naïve animals remained untreated throughout the study. Animals were monitored daily for symptoms of pain and discomfort. The abdominal and hindpaw hypersensitivity were assessed with von Frey microfilaments. Exploratory behaviors were recorded at the baseline, after initiation of treatment, and before study termination. Histopathological changes were examined postmortem in tissues. Collagen accumulation and fibrosis were confirmed with Sirius Red staining. RESULTS: Animals lost weight after oral administration of DBTC and developed persistent inflammatory abdominal and hindpaw hypersensitivity compared to sham-treated controls (P < 0.0001). These pain related secondary mechanical hypersensitivity responses increased more than 2-fold in DBTC-treated animals. The drastically diminished rearing and grooming rates persisted after DBTC administration throughout the study. Gross as well as micropathology at one month confirmed that animals treated with DBTC developed chronic hepatobiliary injuries evidenced with activation of stellate cells, multifocal necrosis, fatty degeneration of hepatocytes, periportal infiltration of inflammatory cells, and prominent biliary ductal dilation. The severity of hepatitis was scored 3.7 ± 0.2 (severe) in DBTC-treated animals vs score 0 (normal) in sham-treated animals. Fibrotic thickening was extensive around portal ducts, in hepatic parenchyma as well as in lobular pancreatic structures and confirmed with Sirius Red histopathology. In addition, pancreatic microarchitecture was presented with distortion of islets, and parenchyma, infiltration of

  10. Overview of the pathogenesis and treatment of chronic inflammatory demyelinating polyneuropathy with intravenous immunoglobulins

    PubMed Central

    Mahdi-Rogers, Mohamed; Rajabally, Yusuf A

    2010-01-01

    Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired heterogeneous disorder of immune origin affecting the peripheral nerves, causing motor weakness and sensory symptoms and signs. The precise pathophysiology of CIDP remains uncertain although B and T cell mechanisms are believed to be implicated. Intravenous immunoglobulins (IVIg) have been shown in a number of trials to be an effective treatment for CIDP. IVIg is thought to exert its immunomodulatory effects by affecting several components of the immune system including B-cells, T-cells, macrophages and complement. This article provides an overview of the pathogenesis of CIDP and of its treatment with IVIg. PMID:20376173

  11. Serum cytokine and chemokine profiles in patients with chronic inflammatory demyelinating polyneuropathy.

    PubMed

    Beppu, Minako; Sawai, Setsu; Misawa, Sonoko; Sogawa, Kazuyuki; Mori, Masahiro; Ishige, Takayuki; Satoh, Mamoru; Nomura, Fumio; Kuwabara, Satoshi

    2015-02-15

    To identify serum cytokine networks specific to chronic inflammatory demyelinating polyneuropathy (CIDP), serum samples of two subgroups (18 patients with typical CIDP and 12 patients with multifocal acquired demyelinating sensory and motor neuropathy [MADSAM]) were analyzed with multiplex magnetic bead-based cytokine assay. TNF-α, HGF, MIP-1β and IL-1β levels were significantly higher in total CIDP patients than in normal controls. Of these, HGF levels were elevated in typical CIDP patients, but not in MADSAM patients. Patients with high HGF levels showed good responses to steroid treatment. Different cytokine profiles among the CIDP subtypes presumably reflect differences in pathophysiology. PMID:25669993

  12. Marine Invertebrate Natural Products for Anti-Inflammatory and Chronic Diseases

    PubMed Central

    Senthilkumar, Kalimuthu; Kim, Se-Kwon

    2013-01-01

    The marine environment represents a relatively available source of functional ingredients that can be applied to various aspects of food processing, storage, and fortification. Moreover, numerous marine invertebrates based compounds have biological activities and also interfere with the pathogenesis of diseases. Isolated compounds from marine invertebrates have been shown to pharmacological activities and are helpful for the invention and discovery of bioactive compounds, primarily for deadly diseases like cancer, acquired immunodeficiency syndrome (AIDS), osteoporosis, and so forth. Extensive research within the last decade has revealed that most chronic illnesses such as cancer, neurological diseases, diabetes, and autoimmune diseases exhibit dysregulation of multiple cell signaling pathways that have been linked to inflammation. On the basis of their bioactive properties, this review focuses on the potential use of marine invertebrate derived compounds on anti-inflammatory and some chronic diseases such as cardiovascular disease, osteoporosis, diabetes, HIV, and cancer. PMID:24489586

  13. Current concepts in chronic inflammatory diseases: Interactions between microbes, cellular metabolism, and inflammation.

    PubMed

    Garn, Holger; Bahn, Sabine; Baune, Bernhard T; Binder, Elisabeth B; Bisgaard, Hans; Chatila, Talal A; Chavakis, Triantafyllos; Culmsee, Carsten; Dannlowski, Udo; Gay, Steffen; Gern, James; Haahtela, Tari; Kircher, Tilo; Müller-Ladner, Ulf; Neurath, Markus F; Preissner, Klaus T; Reinhardt, Christoph; Rook, Graham; Russell, Shannon; Schmeck, Bernd; Stappenbeck, Thaddeus; Steinhoff, Ulrich; van Os, Jim; Weiss, Scott; Zemlin, Michael; Renz, Harald

    2016-07-01

    Recent research indicates that chronic inflammatory diseases, including allergies and autoimmune and neuropsychiatric diseases, share common pathways of cellular and molecular dysregulation. It was the aim of the International von-Behring-Röntgen Symposium (October 16-18, 2014, in Marburg, Germany) to discuss recent developments in this field. These include a concept of biodiversity; the contribution of urbanization, lifestyle factors, and nutrition (eg, vitamin D); and new mechanisms of metabolic and immune dysregulation, such as extracellular and intracellular RNAs and cellular and mitochondrial stress. Epigenetic mechanisms contribute further to altered gene expression and therefore to the development of chronic inflammation. These novel findings provide the foundation for further development of preventive and therapeutic strategies. PMID:27373325

  14. IL-6 promotes acute and chronic inflammatory disease in the absence of SOCS3

    PubMed Central

    Croker, Ben A; Kiu, Hiu; Pellegrini, Marc; Toe, Jesse; Preston, Simon; Metcalf, Donald; O’Donnell, Joanne A; Cengia, Louise H; McArthur, Kate; Nicola, Nicos A; Alexander, Warren S; Roberts, Andrew W

    2011-01-01

    The lack of expression of the Suppressor of Cytokine Signalling-3 (SOCS3) or inactivation of the negative regulatory capacity of SOCS3 has been well documented in rheumatoid arthritis, viral hepatitis and cancer. The specific qualitative and quantitative consequences of SOCS3-deficiency on IL-6-mediated pro- and anti-inflammatory responses remain controversial in vitro and unknown in vivo. Mice with a conditional deletion of SOCS3 in hematopoietic cells develop lethal inflammatory disease during adult life and develop gross histopathological changes during experimental arthritis, typified by elevated IL-6 levels. To clarify the nature of the IL-6 responses in vivo, we generated mice deficient in SOCS3 (SOCS3−/Δvav) or both SOCS3 and IL-6 (IL-6−/−/SOCS3−/Δ vav) and examined responses in models of acute and chronic inflammation. Acute responses to IL-1β were lethal to SOCS3−/Δ vav mice but not IL-6−/−/SOCS3−/Δ vav mice, indicating that IL-6 was required for the lethal inflammation induced by IL-1β. Administration of IL-1β to SOCS3−/Δ vav mice induced systemic apoptosis of lymphocytes in the thymus, spleen and lymph nodes that was dependent on the presence of IL-6. IL-6-deficiency prolonged survival of SOCS3−/Δ vav mice and ameliorated spontaneous inflammatory disease developing during adult life. Infection of SOCS3−/Δ vav mice with LCMV induced a lethal inflammatory response that was dependent on IL-6, despite SOCS3−/Δ vav mice controlling viral replication. We conclude that SOCS3 is required for survival during inflammatory responses and is a critical regulator of IL-6 in vivo. PMID:21519345

  15. The Influence of Chronic Wound Extracts on Inflammatory Cytokine and Histatin Stability

    PubMed Central

    Boink, Mireille A.; Roffel, Sanne; Nazmi, Kamran; van Montfrans, Catherine; Bolscher, Jan G. M.; Gefen, Amit; Veerman, Enno C. I.; Gibbs, Susan

    2016-01-01

    Chronic ulcers represent a major health burden in our society. Despite many available therapies, a large number of ulcers do not heal. Protein based therapies fail in part due to proteolytic activity in the chronic wound bed. The aim of this in vitro study was to determine whether typical inflammatory cytokines and human salivary histatins remain stable when incubated with chronic wound extracts. Furthermore we determined whether a short exposure of histatins or cytokines was sufficient to exert long term effects on fibroblast migration. Stability of human recombinant cytokines IL-6 and CXCL8, and histatin variants (Hst1, Hst2, cyclic Hst1, minimal active domain of Hst1) in the presence of chronic wound extracts isolated from non-healing ulcers, was monitored by capillary zone electrophoresis. Migration-stimulating activity was assessed using a dermal fibroblast wound healing scratch assay. Histatins and cytokines stayed stable in saline for > 24h at 37°C, making them ideal as an off-the-shelf product. However, incubation with chronic wound extracts resulted in serious breakdown of Hst1 and Hst2 (~50% in 8h) and to lesser extent cyclic Hst1 and the minimal active domain of Hst1 (~20% in 8h). The cytokines IL-6 and CXCL8 were more stable in chronic wound extracts (~40% degradation in 96h). An initial 8-hour pulse of histatins or cytokines during a 96-hour study period was sufficient to stimulate fibroblast migration equally well as a continuous 96-hour exposure, indicating that they may possibly be used as novel bioactive therapeutics, exerting their activity for up to four days after a single exposure. PMID:27018788

  16. The Influence of Chronic Wound Extracts on Inflammatory Cytokine and Histatin Stability.

    PubMed

    Boink, Mireille A; Roffel, Sanne; Nazmi, Kamran; van Montfrans, Catherine; Bolscher, Jan G M; Gefen, Amit; Veerman, Enno C I; Gibbs, Susan

    2016-01-01

    Chronic ulcers represent a major health burden in our society. Despite many available therapies, a large number of ulcers do not heal. Protein based therapies fail in part due to proteolytic activity in the chronic wound bed. The aim of this in vitro study was to determine whether typical inflammatory cytokines and human salivary histatins remain stable when incubated with chronic wound extracts. Furthermore we determined whether a short exposure of histatins or cytokines was sufficient to exert long term effects on fibroblast migration. Stability of human recombinant cytokines IL-6 and CXCL8, and histatin variants (Hst1, Hst2, cyclic Hst1, minimal active domain of Hst1) in the presence of chronic wound extracts isolated from non-healing ulcers, was monitored by capillary zone electrophoresis. Migration-stimulating activity was assessed using a dermal fibroblast wound healing scratch assay. Histatins and cytokines stayed stable in saline for > 24 h at 37°C, making them ideal as an off-the-shelf product. However, incubation with chronic wound extracts resulted in serious breakdown of Hst1 and Hst2 (~50% in 8 h) and to lesser extent cyclic Hst1 and the minimal active domain of Hst1 (~20% in 8 h). The cytokines IL-6 and CXCL8 were more stable in chronic wound extracts (~40% degradation in 96 h). An initial 8-hour pulse of histatins or cytokines during a 96-hour study period was sufficient to stimulate fibroblast migration equally well as a continuous 96-hour exposure, indicating that they may possibly be used as novel bioactive therapeutics, exerting their activity for up to four days after a single exposure. PMID:27018788

  17. Chronic fluoride exposure-induced testicular toxicity is associated with inflammatory response in mice.

    PubMed

    Wei, Ruifen; Luo, Guangying; Sun, Zilong; Wang, Shaolin; Wang, Jundong

    2016-06-01

    Previous studies have indicated that fluoride (F) can affect testicular toxicity in humans and rodents. However, the mechanism underlying F-induced testicular toxicity is not well understood. This study was conducted to evaluate the sperm quality, testicular histomorphology and inflammatory response in mice followed F exposure. Healthy male mice were randomly divided into four groups with sodium fluoride (NaF) at 0, 25, 50, 100 mg/L in the drinking water for 180 days. At the end of the exposure, significantly increased percentage of spermatozoa abnormality was found in mice exposed to 50 and 100 mg/L NaF. Disorganized spermatogenic cells, vacuoles in seminiferous tubules and loss and shedding of sperm cells were also observed in the NaF treated group. In addition, chronic F exposure increased testicular interleukin-17(IL-17), interleukin-17 receptor C (IL-17RC), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in transcriptional levels, as well as IL-17 and TNF-α levels in translational levels. Interestingly, we observed that F treated group elevated testicular inducible nitric oxide synthase (iNOS) mRNA level and nitric oxide (NO) concentration. Taken together, these results indicated that testicular inflammatory response could contribute to chronic F exposure induced testicular toxicity in mice. PMID:27031805

  18. Brain injury caused by chronic fetal hypoxemia is mediated by inflammatory cascade activation.

    PubMed

    Guo, Rong; Hou, Weijian; Dong, Yafeng; Yu, Zhiyong; Stites, Josh; Weiner, Carl P

    2010-06-01

    The prevalence of cerebral palsy (CP) shows little temporal or geographic variation and is associated with preterm birth, maternal/fetal infection/inflammation, and fetal growth restriction (IUGR), a potential surrogate for chronic fetal hypoxemia (CHX). We previously demonstrated CHX causes a fetal inflammatory response syndrome (FIRS). Herein, we test the hypothesis that CHX may cause fetal brain injury by upregulating inflammatory cytokine cascades, culminating in apoptosis pathway activation. Time-mated guinea pigs were housed in 12% or 10.5% O(2) for the last 21% of gestation. Chronic fetal hypoxemia increased the lactate/pyruvate and decreased the glutathione (GSH)/oxidized glutathione (GSSH) ratios, confirming a shift to a prooxidant state. The end result was a >30% decrease in hippocampal neuron density. Based on a microarray spotted with 113 cytokines and receptors, 22 genes were upregulated by CHX in proportion to the degree of hypoxia; the findings were confirmed by quantitative polymerase chain reaction (PCR). Thus, CHX triggers fetal brain inflammation inversely proportional to its severity characterized by increased apoptosis and neuronal loss. We suggest CHX fetal brain injury is not directly caused by oxygen deprivation but rather is an adaptive response that becomes maladaptive. PMID:20360591

  19. Chronic inflammatory diseases: do immunological patterns drive the choice of biotechnology drugs? A critical review.

    PubMed

    Sozzani, Silvano; Abbracchio, Maria P; Annese, Vito; Danese, Silvio; De Pità, Ornella; De Sarro, Giovambattista; Maione, Sabatino; Olivieri, Ignazio; Parodi, Aurora; Sarzi-Puttini, Piercarlo

    2014-08-01

    Chronic inflammatory diseases represent a heterogeneous group of conditions that can affect practically any organ or system. An increasing number of biologic agents have been developed to selectively target the cell populations and signaling pathways involved in chronic inflammation, including cytokines, monoclonal antibodies and engineered receptors. This approach has been remarkably successful in alleviating some of the signs and symptoms of refractory autoimmune diseases. The use of this therapeutic strategy is likely to increase with the introduction of biosimilar agents. The different nature of these biological products makes the comparison of their pharmaceutical and clinical characteristics difficult, including safety and potency and these issues may be particularly relevant in the case of biosimilars. In addition, the heterogeneity of autoimmune diseases and of autoimmune patients, further adds to the complexity of choosing the right drug for each patient and predicting efficacy and safety of the treatment. In this review, we summarize actual knowledge about current biological agents and their use in autoimmune diseases, with a special emphasis for rheumatoid arthritis, inflammatory bowel diseases and psoriasis. The purpose of this analysis is to address the most critical issues raised by the rapid advancements in this field over recent years, and to acknowledge the potentially valuable gains brought about by the increasing availability of these new biologic agents. PMID:24697663

  20. ω-3 PUFAs and Resveratrol Differently Modulate Acute and Chronic Inflammatory Processes

    PubMed Central

    Schwager, Joseph; Richard, Nathalie; Riegger, Christoph; Salem, Norman

    2015-01-01

    ω-3 PUFAs and polyphenols have multiple effects on inflammation in vivo and in vitro. The effects of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and resveratrol (RV) were investigated in LPS-stimulated peripheral blood leukocytes (PBLs) (i.e., acute inflammation) and IL-1β activated human chondrocytes (i.e., chronic inflammation). Inflammatory mediators including chemokines, cytokines, interleukins, and PGE2 were measured by multiplex analysis and gene expression was quantified by RT-PCR. In PBLs, RV decreased the secretion of PGE2, CCL5/RANTES, and CXCL8/IL-8 but increased IL-1β, IL-6, and IL-10. In contrast to RV, ω-3 PUFAs augmented the production of PGE2 and CXCL8/IL-8. EPA and DHA similarly affected the pattern of inflammatory mediators. Combination of RV and ω-3 PUFAs exerted synergistic effects on CCL5/RANTES and had additive effects on IL-6 or CXCL8/IL-8. Both ω-3 PUFAs and RV reduced catabolic gene expression (e.g., MMPs, ADAMTS-4, IL-1β, and IL-6) in activated chondrocytes. The data suggest that ω-3 PUFAs and RV differ in the regulation of acute inflammation of peripheral blood leukocytes but have common properties in modulating features related to chronic inflammation of chondrocytes. PMID:26301248

  1. A proposed dosing algorithm for the individualized dosing of human immunoglobulin in chronic inflammatory neuropathies.

    PubMed

    Lunn, Michael P; Ellis, Lauren; Hadden, Robert D; Rajabally, Yusuf A; Winer, John B; Reilly, Mary M

    2016-03-01

    Dosing guidelines for immunoglobulin (Ig) treatment in neurological disorders do not consider variations in Ig half-life or between patients. Individualization of therapy could optimize clinical outcomes and help control costs. We developed an algorithm to optimize Ig dose based on patient's response and present this here as an example of how dosing might be individualized in a pharmacokinetically rational way and how this achieves potential dose and cost savings. Patients are "normalized" with no more than two initial doses of 2 g/kg, identifying responders. A third dose is not administered until the patient's condition deteriorates, allowing a "dose interval" to be set. The dose is then reduced until relapse allowing dose optimization. Using this algorithm, we have individualized Ig doses for 71 chronic inflammatory neuropathy patients. The majority of patients had chronic inflammatory demyelinating polyradiculoneuropathy (n = 39) or multifocal motor neuropathy (n = 24). The mean (standard deviation) dose of Ig administered was 1.4 (0.6) g/kg, with a mean dosing interval of 4.3 weeks (median 4 weeks, range 0.5-10). Use of our standardized algorithm has allowed us to quickly optimize Ig dosing. PMID:26757367

  2. Chronic inflammatory demyelinating polyneuropathy: decreased claudin-5 and relocated ZO-1

    PubMed Central

    Kanda, T; Numata, Y; Mizusawa, H

    2004-01-01

    Objectives: To clarify the dynamics of molecules composing the blood–nerve barrier (BNB) in inflammatory neuropathies. Methods: The expression of four tight junction (TJ) proteins—claudin-1, claudin-5, occludin, and ZO-1—was analysed immunohistochemically in sural nerve biopsy specimens obtained from patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Results: Claudin-1 was detected only in perineurial cells, whereas claudin-5 was present in endothelial cells, irrespective of vessel location or size. Occludin and ZO-1 were found in perineurial cells, in addition to some epineurial and endoneurial endothelial cells. In CIDP, percentages of endoneurial small vessels immunoreactive for claudin-5 were significantly decreased, as were ZO-1 immunoreactive endoneurial small vessels, with staining localised to interfaces between cells. Claudin-1 and occludin immunoreactivity did not differ appreciably between the neuropathies examined. Conclusions: The downregulation of claudin-5 and altered localisation of ZO-1 seen in CIDP specimens may indicate that BNB derangement occurs in inflammatory neuropathies. Further investigation of TJ molecules may suggest new treatments based on properties of the BNB. PMID:15090575

  3. Oxidative and Nitrosative Stress and Immune-Inflammatory Pathways in Patients with Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS)

    PubMed Central

    Morris, Gerwyn; Maes, Michael

    2014-01-01

    Myalgic Encephalomyelitis (ME) / Chronic Fatigue Syndrome (CFS) has been classified as a disease of the central nervous system by the WHO since 1969. Many patients carrying this diagnosis do demonstrate an almost bewildering array of biological abnormalities particularly the presence of oxidative and nitrosative stress (O&NS) and a chronically activated innate immune system. The proposal made herein is that once generated chronically activated O&NS and immune-inflammatory pathways conspire to generate a multitude of self-sustaining and self-amplifying pathological processes which are associated with the onset of ME/CFS. Sources of continuous activation of O&NS and immune-inflammatory pathways in ME/CFS are chronic, intermittent and opportunistic infections, bacterial translocation, autoimmune responses, mitochondrial dysfunctions, activation of the Toll-Like Receptor Radical Cycle, and decreased antioxidant levels. Consequences of chronically activated O&NS and immune-inflammatory pathways in ME/CFS are brain disorders, including neuroinflammation and brain hypometabolism / hypoperfusion, toxic effects of nitric oxide and peroxynitrite, lipid peroxidation and oxidative damage to DNA, secondary autoimmune responses directed against disrupted lipid membrane components and proteins, mitochondrial dysfunctions with a disruption of energy metabolism (e.g. compromised ATP production) and dysfunctional intracellular signaling pathways. The interplay between all of these factors leads to self-amplifying feed forward loops causing a chronic state of activated O&NS, immune-inflammatory and autoimmune pathways which may sustain the disease. PMID:24669210

  4. L-Tetrahydropalmatine alleviates mechanical hyperalgesia in models of chronic inflammatory and neuropathic pain in mice.

    PubMed

    Zhou, Hai-Hui; Wu, Dan-Lian; Gao, Li-Yan; Fang, Yun; Ge, Wei-Hong

    2016-05-01

    Chronic pain is categorized as inflammatory and neuropathic, and there are common mechanisms underlying the generation of each pain state. Such pain is difficult to treat and the treatment at present is inadequate. Corydalis yanhusuo is a traditional Chinese medicine with demonstrated analgesic efficacy in humans. The potential antihyperalgesic effect of its active component is L-tetrahydropalmatine (L-THP). L-THP has been used for the treatment of headache and other mild pain. However, little is known about its analgesic effect on chronic pain and its mechanism. Here, we report that L-THP exerts remarkable antihyperalgesic effects on neuropathic and inflammatory pain in animal models. Neuropathic hypersensitivity was induced by segmental spinal nerve ligation and inflammatory hypersensitivity was induced by an intraplantar injection of complete Freund's adjuvant. To determine the receptor mechanism underlying the antihyperalgesic actions of L-THP, we used SCH23390, an antagonist of a dopamine D1 receptor, in an attempt to block the antihyperalgesic effects of L-THP. We found that L-THP (1-4 mg/kg, i.p.) produced a dose-dependent antihyperalgesic effect in spinal nerve ligation and complete Freund's adjuvant models. The antihyperalgesic effects of L-THP were abolished by a dopamine D1 receptor antagonist SCH23390 (0.02 mg/kg). Furthermore, L-THP (4 mg/kg, i.p.) did not influence motor function. These findings suggest that L-THP may ameliorate mechanical hyperalgesia by enhancing dopamine D1 receptor-mediated dopaminergic transmission. PMID:26981712

  5. Influence of biologic therapy on growth in children with chronic inflammatory connective tissue diseases

    PubMed Central

    Zygmunt, Agnieszka; Biernacka-Zielińska, Małgorzata; Stańczyk, Jerzy; Smolewska, Elżbieta

    2015-01-01

    Objectives Connective tissue diseases (CTD) are a heterogeneous group of chronic inflammatory conditions. One of their complications in children is the inhibition of growth velocity. Due to direct inflammation within the musculoskeletal system as well as glucocorticoid therapy, this feature is the most essential and is mainly expressed in the course of juvenile spondyloarthropathies and juvenile idiopathic arthritis (JIA). Duration of the disease, but predominantly the activity of the inflammatory process, seems to have a significant impact on the abnormal growth profile in children. Effective biological therapy leads to improvement of the patient's clinical condition and also, through the extinction of disease activity and reduction of daily doses of glucocorticosteroids (GCS), it gradually accelerates and normalizes the growth rate in children with CTD. Our objective was to evaluate the impact of biological therapy on growth in children with chronic inflammatory CTD. Material and methods Data from 24 patients with CTD treated with tumor necrosis factor-α-blockers (etanercept, adalimumab, golimumab) and an interleukin-6 receptor blocker (tocilizumab) were reviewed at the time of disease onset, biological treatment initiation and at least 12 up to 24 months onwards. The rate of growth was correlated with the daily doses of GCS, and the type and duration of biological therapy. Results Patient median height, measured as the change in height standard deviation score, was 0.36 ±1.07 at disease onset and –0.13 ±1.02 at biologic therapy initiation. The growth velocity accelerated in 17 patients (70.1%) during the biological treatment. Mean height-SDS improvement between biological treatment initiation up to two years was 0.51 ±0.58. In 47% of patients daily doses of GCS were reduced to 0 mg/kg/day. Conclusions In the treatment of CTD, biological agents restore growth velocity not only by inflammation inhibition, but also through limiting GCS daily doses.

  6. Trigeminal Inflammatory Compression (TIC) injury induces chronic facial pain and susceptibility to anxiety-related behaviors.

    PubMed

    Lyons, D N; Kniffin, T C; Zhang, L P; Danaher, R J; Miller, C S; Bocanegra, J L; Carlson, C R; Westlund, K N

    2015-06-01

    Our laboratory previously developed a novel neuropathic and inflammatory facial pain model for mice referred to as the Trigeminal Inflammatory Compression (TIC) model. Rather than inducing whole nerve ischemia and neuronal loss, this injury induces only slight peripheral nerve demyelination triggering long-term mechanical allodynia and cold hypersensitivity on the ipsilateral whisker pad. The aim of the present study is to further characterize the phenotype of the TIC injury model using specific behavioral assays (i.e. light-dark box, open field exploratory activity, and elevated plus maze) to explore pain- and anxiety-like behaviors associated with this model. Our findings determined that the TIC injury produces hypersensitivity 100% of the time after surgery that persists at least 21 weeks post injury (until the animals are euthanized). Three receptive field sensitivity pattern variations in mice with TIC injury are specified. Animals with TIC injury begin displaying anxiety-like behavior in the light-dark box preference and open field exploratory tests at week eight post injury as compared to sham and naïve animals. Panic anxiety-like behavior was shown in the elevated plus maze in mice with TIC injury if the test was preceded with acoustic startle. Thus, in addition to mechanical and cold hypersensitivity, the present study identified significant anxiety-like behaviors in mice with TIC injury resembling the clinical symptomatology and psychosocial impairments of patients with chronic facial pain. Overall, the TIC injury model's chronicity, reproducibility, and reliability in producing pain- and anxiety-like behaviors demonstrate its usefulness as a chronic neuropathic facial pain model. PMID:25818051

  7. Trigeminal Inflammatory Compression (TIC) Injury Induces Chronic Facial Pain and Susceptibility to Anxiety-Related Behaviors

    PubMed Central

    Lyons, Danielle N.; Kniffin, Tracey C.; Zhang, Liping; Danaher, Robert J.; Miller, Craig S.; Bocanegra, Jose L.; Carlson, Charles R.; Westlund, Karin N.

    2015-01-01

    Our laboratory previously developed a novel neuropathic and inflammatory facial pain model for mice referred to as the Trigeminal Inflammatory Compression (TIC) model. Rather than inducing whole nerve ischemia and neuronal loss, this injury induces only slight peripheral nerve demyelination triggering long-term mechanical allodynia and cold hypersensitivity on the ipsilateral whisker pad. The aim of the present study is to further characterize the phenotype of the TIC injury model using specific behavioral assays (i.e. light-dark box, open field exploratory activity, and elevated plus maze) to explore pain- and anxiety-like behaviors associated with this model. Our findings determined that the TIC injury produces hypersensitivity 100% of the time after surgery that persists at least 21 weeks post injury (until the animals are euthanized). Three receptive field sensitivity pattern variations in mice with TIC injury are specified. Animals with TIC injury begin displaying anxiety-like behavior in the light-dark box preference and open field exploratory tests at week 8 post injury as compared to sham and naïve animals. Panic anxiety-like behavior was shown in the elevated plus maze in mice with TIC injury if the test was preceded with acoustic startle. Thus, in addition to mechanical and cold hypersensitivity, the present study identified significant anxiety-like behaviors in mice with TIC injury which resembling the clinical symptomatology and psychosocial impairments of patients with chronic facial pain. Overall, the TIC injury model’s chronicity, reproducibility, and reliability in producing pain- and anxiety-like behaviors demonstrate its usefulness as a chronic neuropathic facial pain model. PMID:25818051

  8. Chronic low level arsenic exposure evokes inflammatory responses and DNA damage.

    PubMed

    Dutta, Kaustav; Prasad, Priyanka; Sinha, Dona

    2015-08-01

    The cross-sectional study investigated the impact of chronic low level arsenic (As) exposure (11-50μg/L) on CD14 expression and other inflammatory responses in rural women of West Bengal enrolled from control (As level <10μg/L; N, 131) and exposed area (As level 11-50μg/L, N, 142). Atomic absorption spectroscopy revealed that As level in groundwater was higher in endemic areas (22.93±10. 1 vs. 1.61±0.15, P<0.0001) and showed a positive correlation [Pearsons r, 0.9281; 95% confidence interval, 0.8192-0.9724] with As content in nails of the exposed women. Flow cytometric analysis showed that CD 14 expression on monocytes was significantly higher (P<0.001) in exposed women and positively correlated with groundwater As [Pearsons r, 0.9191; 95% confidence interval, 0.7584-0.9745]. Leucocytes and airway cells of As exposed women exhibited up regulation of an inflammatory mediator, tumor necrosis factor-α (TNF-α) and transcription factor, nuclear factor-κB (NF-κB) (P<0.0001). Plasma pro inflammatory cytokines like - TNF-α, interleukins (ILs) - IL-6, IL-8, IL-12 were elevated whereas anti-inflammatory cytokine IL-10 was depleted in the exposed women. Sputa of the exposed women had elevated activity of inflammatory markers - MMP-2 and MMP-9 whereas sera were observed with only increased activity of MMP-9. Airway cells of the exposed women had exacerbated DNA damage than control. Level of oxidative DNA adducts like 8-hydroxy-2'-deoxyguanosine (8OHdG) were also enhanced in plasma of exposed women. Therefore it might be indicated that low level As exposure elicited a pro-inflammatory profile which might have been contributed in part by CD14 expressing monocytes and prolong persistence of pulmonary and systemic inflammation might have promoted oxidative DNA damage in the rural women. PMID:26118750

  9. Inflammatory response in chronic degenerative endometritis mares treated with platelet-rich plasma.

    PubMed

    Reghini, Maria Fernanda S; Ramires Neto, Carlos; Segabinazzi, Lorenzo G; Castro Chaves, Maria Manoela B; Dell'Aqua, Camila de Paula F; Bussiere, Maria Clara C; Dell'Aqua, José Antonio; Papa, Frederico O; Alvarenga, Marco Antonio

    2016-07-15

    Degenerative changes of the endometrium are directly related to age and fertility in mares. Chronic degenerative endometritis (CDE) is correlated with uterine fluid retention and reduced ability to clear uterine inflammation. Recent research in the areas of equine surgery and sports medicine has shown that platelet-rich plasma (PRP) treatment acts as an immunomodulator of the inflammatory response. Therefore, the aim of this study was to determine if the uterine infusion of PRP could modulate the local inflammatory response and modify the intrauterine NO concentrations after artificial insemination (AI) in both normal mares and those with CDE. Thirteen mares with endometrium classified as grade III on the histology (mares with CDE) and eight mares with endometrial histological classification I or II-a normal mares were selected to investigate the effect of PRP therapy. The mares were inseminated with fresh semen in two consecutive cycles in a crossover study design. Thereby, each mare served as its own control and the treatment was performed with intrauterine PRP infusion four hours after AI. The percentage of neutrophils in uterine cytology (CIT, %), uterine fluid accumulation observed on ultrasonography (FLU, mm) and nitric oxide concentration of uterine fluid (NO, μM) were analyzed before and 24 hours after AI. The results reported that mares with CDE (CIT, 68.3 ± 3.27, FLU, 10.7 ± 1.61) have a higher (P < 0.05) intrauterine inflammatory response after AI than normal mares (CIT, 24.4 ± 3.56, FLU, 0), but NO concentrations did not differ (P > 0.05) between categories of mares. In treated cycles with PRP, the intrauterine inflammatory response decrease (P < 0.05) in CDE mares (CDE: CIT, 31.4 ± 6.48, FLU, 5.5 ± 1.28; normal mares: CIT, 13.5 ± 4.31, FLU, 0) when compared with nontreated cycle (CDE: CIT, 68.3 ± 3.27, FLU, 10.7 ± 1.61; NM: CIT, 24.4 ± 3.56, FLU, 0), but did not modify NO concentrations in uterine fluid. Thus, we can

  10. Intestinal barrier dysfunction: implications for chronic inflammatory conditions of the bowel.

    PubMed

    Miner-Williams, Warren M; Moughan, Paul J

    2016-06-01

    The intestinal epithelium of adult humans acts as a differentially permeable barrier that separates the potentially harmful contents of the lumen from the underlying tissues. Any dysfunction of this boundary layer that disturbs the homeostatic equilibrium between the internal and external environments may initiate and sustain a biochemical cascade that results in inflammation of the intestine. Key to such dysfunction are genetic, microbial and other environmental factors that, singularly or in combination, result in chronic inflammation that is symptomatic of inflammatory bowel disease (IBD). The aim of the present review is to assess the scientific evidence to support the hypothesis that defective transepithelial transport mechanisms and the heightened absorption of intact antigenic proinflammatory oligopeptides are important contributing factors in the pathogenesis of IBD. PMID:27087106

  11. Office immunotherapy in chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy.

    PubMed

    Dyck, Peter J; Taylor, Bruce V; Davies, Jenny L; Mauermann, Michelle L; Litchy, William J; Klein, Christopher J; Dyck, P James B

    2015-10-01

    Intravenous immunoglobulin [IVIg], plasma exchange [PE], and corticosteroids are efficacious treatment in chronic inflammatory demyelinating polyneuropathy [CIDP]. IVIg is effective in multifocal motor neuropathy [MMN]. NIS, NIS-weakness, sum scores of raw amplitudes of motor fiber (CMAPs) amplitudes, and Dyck/Rankin score provided reliable measures to detect and scale abnormality and reflect change; they are therefore ideal for office management of response-based immunotherapy (R-IRx) of CIDP. Using efficacious R-IRx, a large early and late therapeutic response (≥ one-fourth were in remission or had recovered) was demonstrated in CIDP. In MMN only an early improvement with late non-significant worsening was observed. The difference in immunotherapy response supports a fundamental difference between CIDP (immune attack on Schwann cells and myelin) and MMN (attack on nodes of Ranvier and axons). PMID:25976871

  12. Treatment of Chronic Inflammatory Demyelinating Polyneuropathy: From Molecular Bases to Practical Considerations

    PubMed Central

    Ripellino, Paolo; Fleetwood, Thomas; Cantello, Roberto; Comi, Cristoforo

    2014-01-01

    Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune disease of the peripheral nervous system, in which both cellular and humoral immune responses are involved. The disease is clinically heterogeneous with some patients displaying pure motor form and others also showing a variable degree of sensory dysfunction; disease evolution may also differ from patient to patient, since monophasic, progressive, and relapsing forms are reported. Underlying such clinical variability there is probably a broad spectrum of molecular dysfunctions that are and will be the target of therapeutic strategies. In this review we first explore the biological bases of current treatments and subsequently we focus on the practical management that must also take into account pharmacoeconomic issues. PMID:24527207

  13. The Effect of Acute and Chronic Morphine on Some Blood Biochemical Parameters in an Inflammatory Condition in Gonadectomized Male Rats

    PubMed Central

    Chahkandi, Mohadeseh; Askari, Nayerreh; Asadikaram, Gholamreza

    2015-01-01

    Background Opiates affect blood factors as well as pain and inflammation in a gender-dependent manner. The aim of the present study was to evaluate the effects of morphine on serum glucose, cholesterol, triglycerides, and urea in gonadectomized and inflammation conditions. Methods Animals were divided as follows: control group, carrageenan and chronic morphine recipients, acute morphine recipients, chronic morphine recipients, carrageenan recipients, acute morphine and carrageenan recipients, gonadectomized group, gonadectomized recipients of carrageenan, gonadectomized recipients of morphine, gonadectomized recipients of chronic morphine, gonadectomized recipients of carrageenan and chronic morphine, gonadectomized recipients of acute morphine and carrageenan. Findings Our results have shown that acute and chronic morphine elevates blood glucose level in the acute and chronic morphine group. Cholesterol level has shown to be increasing in the morphine and carrageenan recipient group compared with a group which merely received morphine. Triglyceride has shown to be decreasing in acute and chronic morphine recipient group compared with control group. A significant increase in serum urea was observed in acute and chronic morphine recipients compared with the carrageenan recipient group. Conclusion Morphine alters the serum glucose, cholesterol, triglyceride, and urea in the normal and inflammatory conditions differently, hence, this finding should be considered in the patients who use morphine as a relief of pain, especially in an inflammatory condition. PMID:26885349

  14. Serum thymosin α 1 levels in patients with chronic inflammatory autoimmune diseases.

    PubMed

    Pica, F; Chimenti, M S; Gaziano, R; Buè, C; Casalinuovo, I A; Triggianese, P; Conigliaro, P; Di Carlo, D; Cordero, V; Adorno, G; Volpi, A; Perricone, R; Garaci, E

    2016-10-01

    Thymosin alpha 1 (Tα1) is a powerful modulator of immunity and inflammation. Despite years of studies, there are a few reports evaluating serum Tα1 in health and disease. We studied a cohort of healthy individuals in comparison with patients affected by chronic inflammatory autoimmune diseases. Sera from 120 blood donors (healthy controls, HC), 120 patients with psoriatic arthritis (PsA), 40 with rheumatoid arthritis (RA) and 40 with systemic lupus erythematosus (SLE), attending the Transfusion Medicine or the Rheumatology Clinic at the Policlinico Tor Vergata, Rome, Italy, were tested for Tα1 content by means of a commercial enzyme-linked immunosorbent assay (ELISA) kit. Data were analysed in relation to demographic and clinical characteristics of patients and controls. A gender difference was found in the HC group, where females had lower serum Tα1 levels than males (P < 0·0001). Patients had lower serum Tα1 levels than HC (P < 0·0001), the lowest were observed in PsA group (P < 0·0001 versus all the other groups). Among all patients, those who at the time of blood collection were taking disease-modifying anti-rheumatic drugs (DMARD) plus steroids had significantly higher Tα1 levels than those taking DMARD alone (P = 0·044) or no treatment (P < 0·0001), but not of those taking steroids alone (P = 0·280). However, whichever type of treatment was taken by the patients, serum Tα1 was still significantly lower than in HC and there was no treatment-related difference in PsA group. Further prospective studies are necessary to confirm and deepen these observations. They might improve our understanding on the regulatory role of Tα1 in health and disease and increase our knowledge of the pathogenesis of chronic inflammatory autoimmune diseases. PMID:27350088

  15. The Case for Increased Physical Activity in Chronic Inflammatory Bowel Disease: A Brief Review.

    PubMed

    Shephard, R J

    2016-06-01

    Regular physical activity reduces the risk of colon cancer, but there is little information on the merits of such activity in the prevention and management of chronic inflammatory bowel disease (CIBD). The present systematic review thus documents current levels of habitual physical activity and aerobic and muscular function in CIBD, and examines the safety, practicality and efficacy of exercise programmes in countering the disease process, correcting functional deficits and enhancing quality of life. A systematic search of the Ovid/Medline database from January 1996 to May 2015 linked the terms physical activity/motor activity/physical fitness/physical training/physical education/training/exercise/exercise therapy with Crohn's disease/colitis/ulcerative colitis/inflammatory bowel disease, supplementing this information by a scanning of reference lists and personal files.12 of 16 published studies show a low level of habitual physical activity in CIBD, with sub-normal values for aerobic power, lean tissue mass and muscular strength. 3 of 4 studies suggest physical activity may reduce the risk of developing IBD, and 11 interventions all note that exercise programmes are well tolerated with some decreases of disease activity, and functional gains leading to an increased health-related quality of life. Moreover, programme compliance rates compare favourably with those seen in the treatment of other chronic conditions. More information on mechanisms is needed, but regular moderate aerobic and/or resistance exercise improves the health status of patients with CIBD both by modulating immune function and by improving physical function. A regular exercise programme should thus become an important component in the management of CIBD. PMID:27116344

  16. [Nondeficiency chronic polyneuropathies in celiac disease in adults (2 cases with inflammatory neuromuscular vascularitis)].

    PubMed

    Bernier, J J; Buge, A; Rambaud, J C; Rancurel, G; Hauw, J J; Modigliani, R; Denvil, D

    1976-10-01

    The neurological and muscular complications seen in coeliac disease in adults are usually attributed to deficiency secondary to malabsorption. Amongst them, however, there exists a very rare cateogory, described by Cooke et al. (1966) taking the form of a chronic myeloneuropathy which cannot be explained in terms of the malabsorption syndrome. Our two cases of gluten intolerance enteropathy, confirmed by biopsy before and after diet, fell into this group of polyneuropathies. The patients, both women, suffered from an essentially sensory ataxic polyneuropathy with accessory motor component with pyramidal and posterior column signs. CSF findings showed a meningeal inflammatory reaction in one of the two cases. These neurological signs, appearing paradoxically during a digestive disease cured by diet, evolve chronically but become stabilised with corticosteroid therapy. Any vitamin deficiency may be excluded in the aetiology of these problems. Neuropathological study of neuromuscular biopsies in very fine serial sections confirmed the mild peripheral nervous involvement but revealed identical inflammatory lesions in the nerve and muscle which were remarkable by virtue of their very highly segmentally selective micro-vasculitis appearance. In these two cases, general, clinical and biological arguments, as well as the type of histological lesion, make it possible to exclude monoclonal gammapathies, malignant haemopathies, amyloidosis and the major collagen diseases. This micro-vasculitis, having transient forms with P.A.N. is no less distinctive, and may be integrated into the provisional group of "allergic angeitis", related to physiopathology of circulating immune complexes and very fashionable in theories as to the mechanism of gluten-sensitive enteropathies. The exact nature of the link between the latter and these types of polyneuropathy remains unknown. PMID:1008365

  17. Fibroblast contraction of collagen lattices in vitro: inhibition by chronic inflammatory cell mediators.

    PubMed

    Ehrlich, H P; Wyler, D J

    1983-09-01

    Fibroblast-populated collagen lattices (FPCL), prepared in petri dishes with serum-containing culture medium and incubated at 37 degrees C, undergo progressive and symmetric contraction (reduction in size) over a period of days. The in vitro contraction process requires viable cells with intact cytoskeletal elements, is associated with cell elongation, and is believed to represent a fibroblast function which also occurs in vivo during wound healing and tissue fibrosis. We report that soluble mediators elaborated by chronic inflammatory cells cultured in vitro, when added to FPCL, inhibit lattice contraction. Granulomas, isolated from the liver of Schistosoma mansoni-infected mice, secrete a factor(s) with an estimated molecular weight between 13,700 and 43,000 daltons (gel filtration: Sephadex G-200) and pI = 6 (preparative isoelectrofocusing in granular gel) which inhibits lattice contraction but is not toxic to fibroblasts. Supernatants (cell-free conditioned culture medium) of cultured macrophages isolated from these granulomas also contain this activity. The contraction inhibitory activity present in granuloma culture supernatants is abrogated by the addition of indomethacin to the lattices, while the addition of prostaglandin E2 (PGE2) alone to lattices inhibits contraction. Furthermore, culture supernatants interfere with fibroblast elongation in lattices. We propose that the ability of fibroblasts to contract collagen lattices in vitro and a fibrotic mass in vivo may be regulated by soluble products of chronic inflammatory cells, including macrophages. This process may be mediated by fibroblast-derived prostaglandins which alter cytoskeletal functions and has implications for understanding regulation of tissue fibrogenesis in a variety of diseases. PMID:6885932

  18. The Anti-Inflammatory Actions of Auricular Point Acupressure for Chronic Low Back Pain.

    PubMed

    Lin, Wei-Chun; Yeh, Chao Hsing; Chien, Lung-Chang; Morone, Natalia E; Glick, Ronald M; Albers, Kathryn M

    2015-01-01

    Background. Auricular point acupressure (APA) is a promising treatment for pain management. Few studies have investigated the physiological mechanisms of APA analgesics. Method. In this pilot randomized clinical trial (RCT), a 4-week APA treatment was used to manage chronic low back pain (CLBP). Sixty-one participants were randomized into a real APA group (n = 32) or a sham APA group (n = 29). Blood samples, pain intensity, and physical function were collected at baseline and after 4 weeks of treatment. Results. Subjects in the real APA group reported a 56% reduction of pain intensity and a 26% improvement in physical function. Serum blood samples showed (1) a decrease in IL-1β, IL-2, IL-6, and calcitonin gene-related peptide [CGRP] and (2) an increase in IL-4. In contrast, subjects in the sham APA group (1) reported a 9% reduction in pain and a 2% improvement in physical function and (2) exhibited minimal changes of inflammatory cytokines and neuropeptides. Statistically significant differences in IL-4 and CGRP expression between the real and sham APA groups were verified. Conclusion. These findings suggest that APA treatment affects pain intensity through modulation of the immune system, as reflected by APA-induced changes in serum inflammatory cytokine and neuropeptide levels. PMID:26170869

  19. Systemic Inflammatory Response to Smoking in Chronic Obstructive Pulmonary Disease: Evidence of a Gender Effect

    PubMed Central

    Cruz, Tamara; Kalko, Susana Graciela; Agustí, Alvar

    2014-01-01

    Background Tobacco smoking is the main risk factor of chronic obstructive pulmonary disease (COPD) but not all smokers develop the disease. An abnormal pulmonary and systemic inflammatory response to smoking is thought to play a major pathogenic role in COPD, but this has never been tested directly. Methods We studied the systemic biomarker and leukocyte transcriptomic response (Affymetrix microarrays) to smoking exposure in 10 smokers with COPD and 10 smokers with normal spirometry. We also studied 10 healthy never smokers (not exposed to smoking) as controls. Because some aspects of COPD may differ in males and females, and the inflammatory response to other stressors (infection) might be different in man and women, we stratified participant recruitment by sex. Differentially expressed genes were validated by q-PCR. Ontology enrichment was evaluated and interaction networks inferred. Results Principal component analysis identified sex differences in the leukocyte transcriptomic response to acute smoking. In both genders, we identified genes that were differentially expressed in response to smoking exclusively in COPD patients (COPD related signature) or smokers with normal spirometry (Smoking related signature), their ontologies and interaction networks. Conclusions The use of an experimental intervention (smoking exposure) to investigate the transcriptomic response of peripheral leukocytes in COPD is a step beyond the standard case-control transcriptomic profiling carried out so far, and has facilitated the identification of novel COPD and Smoking expression related signatures which differ in males and females. PMID:24830457

  20. The Anti-Inflammatory Actions of Auricular Point Acupressure for Chronic Low Back Pain

    PubMed Central

    Lin, Wei-Chun; Yeh, Chao Hsing; Chien, Lung-Chang; Morone, Natalia E.; Glick, Ronald M.; Albers, Kathryn M.

    2015-01-01

    Background. Auricular point acupressure (APA) is a promising treatment for pain management. Few studies have investigated the physiological mechanisms of APA analgesics. Method. In this pilot randomized clinical trial (RCT), a 4-week APA treatment was used to manage chronic low back pain (CLBP). Sixty-one participants were randomized into a real APA group (n = 32) or a sham APA group (n = 29). Blood samples, pain intensity, and physical function were collected at baseline and after 4 weeks of treatment. Results. Subjects in the real APA group reported a 56% reduction of pain intensity and a 26% improvement in physical function. Serum blood samples showed (1) a decrease in IL-1β, IL-2, IL-6, and calcitonin gene-related peptide [CGRP] and (2) an increase in IL-4. In contrast, subjects in the sham APA group (1) reported a 9% reduction in pain and a 2% improvement in physical function and (2) exhibited minimal changes of inflammatory cytokines and neuropeptides. Statistically significant differences in IL-4 and CGRP expression between the real and sham APA groups were verified. Conclusion. These findings suggest that APA treatment affects pain intensity through modulation of the immune system, as reflected by APA-induced changes in serum inflammatory cytokine and neuropeptide levels. PMID:26170869

  1. Infection of the sigmoid colon during TNFα antagonist therapy for chronic inflammatory joint disease.

    PubMed

    Moyano, Chantal; Beldjerd, Mounir; Pécourneau, Virginie; Billey, Thierry; Lassoued, Slim

    2014-05-01

    We report 7 cases of sigmoid colon infection in patients taking TNFα antagonist therapy to treat chronic inflammatory joint disease. There were 5 women and 2 men with a mean age of 57.5 years (range, 21-77 years). The presenting symptoms were abdominal pain, bowel habit changes, and a fever. These symptoms developed within 6 months after starting TNFα antagonist therapy in 5 of the 7 patients. Empirical antibiotic therapy was used in all 7 patients. Surgical colectomy was performed in 4 patients, including 1 who required a temporary Hartmann's procedure. The risk of infection associated with TNFα antagonist therapy is well documented. However, few cases of colon infection have been reported and little is known about this potentially severe complication. Glucocorticoids or non-steroidal anti-inflammatory drugs may worsen the infection, particularly as they can attenuate the clinical symptoms, thereby delaying the diagnosis. A history of sigmoid colon infection, diverticulosis, and/or diverticulitis must be sought before starting treatment with a biological agent. Prophylactic treatment may be considered if such a history is found. Diagnostic investigations are in order to develop a standardized management strategy in patients with a history of intestinal tract infection. PMID:24176737

  2. Location of tumour necrosis factor alpha by immunohistochemistry in chronic inflammatory bowel disease.

    PubMed Central

    Murch, S H; Braegger, C P; Walker-Smith, J A; MacDonald, T T

    1993-01-01

    This study determined the location and tissue density of cells immunoreactive for tumour necrosis factor alpha (TNF alpha) in intestinal specimens from 24 patients with chronic inflammatory bowel disease (15 with Crohn's disease, nine with ulcerative colitis) and 11 controls. There was significantly increased density of TNF alpha immunoreactive cells in the lamina propria of both ulcerative colitis and Crohn's disease specimens, although the distribution of these cells differed in the two conditions. In ulcerative colitis most of the TNF alpha immunoreactivity was seen in the subepithelial macrophages, with comparatively less in the deep lamina propria, while in Crohn's disease immunoreactive cells were distributed evenly throughout the lamina propria. Increased submucosal immunoreactivity was found only in Crohn's disease, in which TNF alpha positive macrophages tended to cluster around arterioles and venules, often infiltrating and disrupting vascular endothelium. It is suggested that this degree of TNF alpha production probably contributes significantly to the pathogenesis of both Crohn's disease and ulcerative colitis, by impairing the integrity of epithelial and endothelial membranes, increasing inflammatory cell recruitment, and by prothrombotic effects on the vascular endothelium. Images Figure 2 PMID:8031350

  3. Inflammatory and Metabolic Alterations of Kager's Fat Pad in Chronic Achilles Tendinopathy

    PubMed Central

    Fredberg, Ulrich; Kjær, Søren G.; Quistorff, Bjørn; Langberg, Henning; Hansen, Jacob B.

    2015-01-01

    Background Achilles tendinopathy is a painful inflammatory condition characterized by swelling, stiffness and reduced function of the Achilles tendon. Kager’s fat pad is an adipose tissue located in the area anterior to the Achilles tendon. Observations reveal a close physical interplay between Kager’s fat pad and its surrounding structures during movement of the ankle, suggesting that Kager’s fat pad may stabilize and protect the mechanical function of the ankle joint. Aim The aim of this study was to characterize whether Achilles tendinopathy was accompanied by changes in expression of inflammatory markers and metabolic enzymes in Kager’s fat pad. Methods A biopsy was taken from Kager’s fat pad from 31 patients with chronic Achilles tendinopathy and from 13 healthy individuals. Gene expression was measured by reverse transcription-quantitative PCR. Focus was on genes related to inflammation and lipid metabolism. Results Expression of the majority of analyzed inflammatory marker genes was increased in patients with Achilles tendinopathy compared to that in healthy controls. Expression patterns of the patient group were consistent with reduced lipolysis and increased fatty acid β-oxidation. In the fat pad, the pain-signaling neuropeptide substance P was found to be present in one third of the subjects in the Achilles tendinopathy group but in none of the healthy controls. Conclusion Gene expression changes in Achilles tendinopathy patient samples were consistent with Kager’s fat pad being more inflamed than in the healthy control group. Additionally, the results indicate an altered lipid metabolism in Kager’s fat pad of Achilles tendinopathy patients. PMID:25996876

  4. Chronic cigarette smoke exposure induces microbial and inflammatory shifts and mucin changes in the murine gut.

    PubMed

    Allais, Liesbeth; Kerckhof, Frederiek-Maarten; Verschuere, Stephanie; Bracke, Ken R; De Smet, Rebecca; Laukens, Debby; Van den Abbeele, Pieter; De Vos, Martine; Boon, Nico; Brusselle, Guy G; Cuvelier, Claude A; Van de Wiele, Tom

    2016-05-01

    Inflammatory bowel diseases (IBD) are complex multifactorial diseases characterized by an inappropriate host response to an altered commensal microbiome and dysfunctional mucus barrier. Cigarette smoking is the best known environmental risk factor in IBD. Here, we studied the influence of chronic smoke exposure on the gut microbiome, mucus layer composition and immune factors in conventional mice. We compared smoke-exposed with air-exposed mice (n = 12) after a smoke exposure of 24 weeks. Both Illumina sequencing (n = 6) and denaturing gradient gel electrophoresis (n = 12) showed that bacterial activity and community structure were significantly altered in the colon due to smoke exposure. Interestingly, an increase of Lachnospiraceae sp. activity in the colon was observed. Also, the mRNA expression of Muc2 and Muc3 increased in the ileum, whereas Muc4 increased in the distal colon of smoke-exposed mice (n = 6). Furthermore, we observed increased Cxcl2 and decreased Ifn-γ in the ileum, and increased Il-6 and decreased Tgf-β in the proximal colon. Tight junction gene expression remained unchanged. We infer that the modulating role of chronic smoke exposure as a latently present risk factor in the gut may be driven by the altered epithelial mucus profiles and changes in microbiome composition and immune factors. PMID:26033517

  5. Cell-Permeable Peptide Tat-PSD-95 PDZ2 Inhibits Chronic Inflammatory Pain Behaviors in Mice

    PubMed Central

    Tao, Feng; Su, Qingning; Johns, Roger A.

    2009-01-01

    Inflammatory conditions can lead to persistent debilitating pain, and the activation of N-methyl-D-aspartate receptors (NMDARs) has been shown to play an important role in the processing of inflammatory pain. Postsynaptic density protein-95 (PSD-95), a scaffolding protein, has been identified to interact with NMDARs at neuronal synapses of the central nervous system. However, the role of these interactions in the central sensitization of nociceptive processing has not been defined. In the present study, we investigated the effect of disrupting NMDAR/PSD-95 interactions on chronic inflammatory pain behaviors. We constructed a fusion peptide, Tat-PSD-95 PDZ2, comprising the second PDZ domain of PSD-95, to disrupt specificallyNMDARs/PSD-95 protein interactions. Western blot analysis showed that Tat-PSD-95 PDZ2 intraperitoneally injected into mice was delivered intracellularly into neurons in the central nervous system. By in vitro and in vivo binding assays, we found that the Tat-PSD-95 PDZ2 dose-dependently inhibited the interactions between NMDARs and PSD-95. Furthermore, behavioral testing showed that mice given Tat-PSD-95 PDZ2 exhibited significantly reduced complete Freund’s adjuvant-induced chronic inflammatory pain behaviors compared to the vehicle-treated group. Our results indicate that by disrupting NMDAR/PSD-95 protein interactions, the cell-permeable fusion peptide Tat-PSD-95 PDZ2 provides a new target and approach for chronic inflammatory pain therapy. PMID:18781143

  6. Faecal alpha-1-antitrypsin and excretion of 111indium granulocytes in assessment of disease activity in chronic inflammatory bowel diseases.

    PubMed Central

    Fischbach, W; Becker, W; Mössner, J; Koch, W; Reiners, C

    1987-01-01

    Intestinal protein loss in chronic inflammatory bowel diseases may be easily determined by measurement of alpha-1-antitrypsin (alpha 1-AT) stool concentration and alpha 1-AT clearance. Both parameters were significantly raised in 36 and 34 patients respectively with chronic inflammatory bowel diseases, compared with eight patients with non-inflammatory bowel diseases, or 19 healthy volunteers. There was wide range of overlap between active and inactive inflammatory disease. Contrary to serum alpha 1-AT, faecal excretion and clearance of alpha 1-AT did not correlate with ESR, serum-albumin, orosomucoid, and two indices of disease activity. A comparison of alpha 1-AT faecal excretion and clearance with the faecal excretion of 111In labelled granulocytes in 27 patients with chronic inflammatory bowel diseases, showed no correlation between the intestinal protein loss and this highly specific marker of intestinal inflammation. Enteric protein loss expressed by faecal excretion and clearance of alpha 1-AT does not depend on mucosal inflammation only, but may be influenced by other factors. PMID:3495470

  7. Chronic inflammatory state in sickle cell anemia patients is associated with HBB(*)S haplotype.

    PubMed

    Bandeira, Izabel C J; Rocha, Lillianne B S; Barbosa, Maritza C; Elias, Darcielle B D; Querioz, José A N; Freitas, Max Vitor Carioca; Gonçalves, Romélia P

    2014-02-01

    The chronic inflammatory state in sickle cell anemia (SCA) is associated with several factors such as the following: endothelial damage; increased production of reactive oxygen species; hemolysis; increased expression of adhesion molecules by leukocytes, erythrocytes, and platelets; and increased production of proinflammatory cytokines. Genetic characteristics affecting the clinical severity of SCA include variations in the hemoglobin F (HbF) level, coexistence of alpha-thalassemia, and the haplotype associated with the HbS gene. The different haplotypes of SCA are Bantu, Benin, Senegal, Cameroon, and Arab-Indian. These haplotypes are associated with ethnic groups and also based on the geographical origin. Studies have shown that the Bantu haplotype is associated with higher incidence of clinical complications than the other haplotypes and is therefore considered to have the worst prognosis. This study aimed to evaluate the profile of the proinflammatory cytokines interleukin-6, tumor necrosis factor-α, and interleukin-17 in patients with SCA and also to assess the haplotypes associated with beta globin cluster S (HBB(*)S). We analyzed a total of 62 patients who had SCA and had been treated with hydroxyurea; they had received a dose ranging between 15 and 25 (20.0±0.6)mg/kg/day for 6-60 (18±3.4)months; their data were compared with those for 30 normal individuals. The presence of HbS was detected and the haplotypes of the beta S gene cluster were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Our study demonstrated that SCA patients have increased inflammatory profile when compared to the healthy individuals. Further, analysis of the association between the haplotypes and inflammatory profile showed that the levels of IL-6 and TNF-α were greater in subjects with the Bantu/Bantu haplotype than in subjects with the Benin/Benin haplotype. The Bantu/Benin haplotype individuals had lower levels of cytokines than those with

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

    PubMed Central

    2012-01-01

    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. PMID:22510431

  9. Nutmeg oil alleviates chronic inflammatory pain through inhibition of COX-2 expression and substance P release in vivo

    PubMed Central

    Zhang, Wei Kevin; Tao, Shan-Shan; Li, Ting-Ting; Li, Yu-Sang; Li, Xiao-Jun; Tang, He-Bin; Cong, Ren-Huai; Ma, Fang-Li; Wan, Chu-Jun

    2016-01-01

    Background Chronic pain, or sometimes referred to as persistent pain, reduces the life quality of patients who are suffering from chronic diseases such as inflammatory diseases, cancer and diabetes. Hence, herbal medicines draw many attentions and have been shown effective in the treatment or relief of pain. Methods and Results Here in this study, we used the CFA-injected rats as a sustainable pain model to test the anti-inflammatory and analgesic effect of nutmeg oil, a spice flavor additive to beverages and baked goods produced from the seed of Myristica fragrans tree. Conclusions We have demonstrated that nutmeg oil could potentially alleviate the CFA-injection induced joint swelling, mechanical allodynia and heat hyperanalgesia of rats through inhibition of COX-2 expression and blood substance P level, which made it possible for nutmeg oil to be a potential chronic pain reliever. PMID:27121041

  10. [THE CHARACTERISTICS OF MORPHOLOGY OF BIOFILM OF PERIODONTIUM UNDER INFLAMMATORY DISEASES OF GUMS (CHRONIC CATARRHAL GINGIVITIS, CHRONIC PERIODONTITIS, CANDIDA-ASSOCIATED PERIODONTITIS) ACCORDING RESULTS OF ELECTRONIC MICROSCOPY].

    PubMed

    Ippolitov, E V; Didenko, L V; Tzarev, V N

    2015-12-01

    The study was carried out to analyze morphology of biofilm of periodontium and to develop electronic microscopic criteria of differentiated diagnostic of inflammatory diseases of gums. The scanning electronic microscopy was applied to analyze samples of bioflm of periodont from 70 patients. Including ten patients with every nosologic form of groups with chronic catarrhal periodontitis. of light, mean and severe degree, chronic catarrhal gingivitis, Candida-associated paroperiodontitis and 20 healthy persons with intact periodontium. The analysis was implemented using dual-beam scanning electronic microscope Quanta 200 3D (FEI company, USA) and walk-through electronic micJEM 100B (JEOL, Japan). To detect marker DNA of periodont pathogenic bacteria in analyzed samples the kit of reagentsfor polymerase chain reaction "MultiDent-5" ("GenLab", Russia). The scanning electronic microscopy in combination with transmission electronic microscopy and polymerase chain reaction permits analyzing structure, composition and degree of development of biofilm of periodontium and to apply differentiated diagnostic of different nosologic forms of inflammatory diseases of periodontium, including light form of chronic periodontitis and gingivitis. The electronic microscopical indications of diseases ofperiodontium of inflammatory character are established: catarrhal gingivitis, (coccal morphological alternate), chronic periodontitis (bacillary morphological alternate), Candida-associated periodontitis (Candida morphological alternate of biofilm ofperiodontium). PMID:27032256

  11. Gestational diabetes induces chronic hypoxia stress and excessive inflammatory response in murine placenta

    PubMed Central

    Li, Hua-Ping; Chen, Xuan; Li, Ming-Qing

    2013-01-01

    Metabolic impairments in maternal obesity and gestational diabetes mellitus (GDM) induce an abnormal environment in peripheral blood and cause vascular structure alterations which affect the placental development and function. A GDM model was developed using C57BL/6J female mice fed with high fat food (HF) (40% energy from fat) and a control group with control food (CF) (14% energy from fat) for 14 weeks before mating and throughout the gestation period. A subset of dams was sacrificed at gestational day (GD) 18.5 to evaluate the fetal and placental development. HF-fed dams exhibited significant increase in the maternal weight gain and homeostasis model assessment for insulin resistance index (HOMA-IR), impaired insulin secretion of glucose stimulus and glucose clearance of insulin stimulus before pregnancy; in addition, they also had the increase in the fetal and placental weight. HF-fed dams at GD 18.5 showed the high level of circulating maternal inflammation factors and were associated with increased oxidative stress and hypoxia in the labyrinth, abnormal vascular development with a high level of hypoxia inducible factor-1α (HIF-1α) and VEGF-A expression, but without a parallel increase in CD31 level; were induced an exaggerated inflammatory response in placental vascular endothelial cell. Our findings show that GDM induces more maternal weight gain and fetus weight, with abnormal maternal circulating metabolic and inflammation factors, and forms a placental hypoxia environment and impacts the placental vascular development. Our findings indicate that gestational diabetes induce excessive chronic hypoxia stress and inflammatory response in placentas which may contribute mechanisms to the high risks of perinatal complications of obesity and GDM mothers. PMID:23573311

  12. Contrasting Pattern of Chronic Inflammatory Bowel Disease in Primary and Autoimmune Sclerosing Cholangitis

    PubMed Central

    Bjarnason, Ingvar; Hayee, Bu; Pavlidis, Polychronis; Kvasnovsky, Charlotte; Scalori, Astrid; Sisson, Guy; Charlesworth, Annika; Shaikh, Hizbullah; Bjornsson, Einar; Heneghan, Michael A.

    2015-01-01

    Background Primary sclerosing cholangitis (PSC) and autoimmune sclerosing cholangitis (AISC) are related, but distinct chronic liver diseases. PSC is associated with a high prevalence of ulcerative colitis while the intestinal inflammation associated with AISC is less well characterised. Aims To assess and contrast aspects of intestinal inflammation in patients with AISC and PSC and compare the clinical features with those of patients with ulcerative colitis and Crohn's disease. Methods 23 and 22 patients with AISC and PSC, respectively, underwent review of colonoscopy and biopsy findings, capsule enteroscopy and assessment of clinical and inflammatory (faecal calprotectin) disease activity, which was compared with that of patients with ulcerative colitis and Crohn's disease (n = 55 each). Findings Five and 6 patients with AISC and PSC, respectively, had normal colonoscopy and faecal calprotectin levels of 34.4 ± 8.3 and 39.7 ± 8.4 μg/g, respectively (normal < 50 μg/g), whereas 18 and 16, respectively, had identical variably severe, right sided colitis with frequent rectal sparing, consistent with ulcerative colitis. Mean (± SD) faecal calprotectin levels did not differ significantly (p > 0.05) between patients with intestinal inflammation in AISC (588 ± 549 μg/g), PSC (421 ± 351 μg/g), ulcerative colitis (501 ± 656 μg/g) or Crohn's disease (476 ± 571 μg/g). Capsule enteroscopy showed that 7 of 18 (39%) (p < 0.03) of those with AISC had small bowel mucosal breaks whereas no patient with PSC had these findings. Interpretation Collectively these findings lend support to the suggestion that the chronic inflammatory bowel disease associated with PSC and in particular AISC may represent a distinct nosologic entity different from classic ulcerative colitis and Crohn's disease. PMID:26629548

  13. Detection of inflammatory biomarkers in saliva and urine: Potential in diagnosis, prevention, and treatment for chronic diseases.

    PubMed

    Prasad, Sahdeo; Tyagi, Amit K; Aggarwal, Bharat B

    2016-04-01

    Inflammation is a part of the complex biological response of inflammatory cells to harmful stimuli, such as pathogens, irritants, or damaged cells. This inflammation has been linked to several chronic diseases including cancer, atherosclerosis, rheumatoid arthritis, and multiple sclerosis. Major biomarkers of inflammation include tumor necrosis factor, interleukins (IL)-1, IL-6, IL-8, chemokines, cyclooxygenase, 5-lipooxygenase, and C-reactive protein, all of which are regulated by the transcription factor nuclear factor-kappaB. Although examining inflammatory biomarkers in blood is a standard practice, its identification in saliva and/or urine is more convenient and non-invasive. In this review, we aim to (1) discuss the detection of these inflammatory biomarkers in urine and saliva; (2) advantages of using salivary and urinary inflammatory biomarkers over blood, while also weighing on the challenges and/or limitations of their use; (3) examine their role(s) in connection with diagnosis, prevention, treatment, and drug development for several chronic diseases with inflammatory consequences, including cancer; and (4) explore the use of innovative salivary and urine based biosensor strategies that may permit the testing of biomarkers quickly, reliably, and cost-effectively, in a decentralized setting. PMID:27013544

  14. Aspirin or Nonsteroidal Anti-inflammatory Drug-Exacerbated Chronic Rhinosinusitis.

    PubMed

    Ledford, Dennis K; Lockey, Richard F

    2016-01-01

    Aspirin (ASA)-exacerbated respiratory disease (AERD) is characterized by upper airway congestion due to eosinophilic inflammation of the nasal and sinus membranes and nasal polyposis, associated with increased leukotriene production that is further accentuated by ASA or other nonsteroidal anti-inflammatory drug (NSAID) ingestion. It occurs in 5% to 10% of subjects with chronic rhinosinusitis (CRS) and in 15% to 40% of those with nasal polyposis. Although AERD with CRS is usually associated with asthma, this is not always the case. The eosinophilic airway inflammation and symptoms precede clinical reactions to ASA or other NSAIDs, but ultimately affected subjects experience worsening of symptoms with ingestion of ASA/NSAIDs. The endotypic mechanism for this worsening is related to a chronic increase in leukotriene and a decrease in prostaglandin production, particularly prostaglandin E2, that is further aggravated by the inhibition of cycloxgenase I. IgE does not likely play a role in the pathogenesis of the disease although nasal and sinus staphylococcal infection increases local IgE level and may increase total IgE and specific IgE levels. Genetic studies suggest that multiple genes may be involved, but the genetic abnormalities may differ in affected subjects from different ethnicities and candidate genes have not been confirmed in multiple studies. Genome-wide association studies have not been revealing. The phenotype is recognized by the mucosal inflammation and worsening of symptoms acutely with ASA/NSAID. There is clinical improvement with ASA desensitization followed by regular ingestion of ASA or other NSAIDs. Further understanding of this unique phenotype and endotype of CRS will likely improve the understanding of other eosinophilic airway diseases. PMID:27393773

  15. Antileukotriene Reverts the Early Effects of Inflammatory Response of Distal Parenchyma in Experimental Chronic Allergic Inflammation

    PubMed Central

    Gobbato, Nathália Brandão; de Souza, Flávia Castro Ribas; Fumagalli, Stella Bruna Napolitano; Lopes, Fernanda Degobbi Tenório Quirino dos Santos; Prado, Carla Máximo; Martins, Milton Arruda; Tibério, Iolanda de Fátima Lopes Calvo; Leick, Edna Aparecida

    2013-01-01

    Aims. Compare the effects of montelukast or dexamethasone in distal lung parenchyma and airway walls of guinea pigs (GP) with chronic allergic inflammation. Methods. GP have inhaled ovalbumin (OVA group-2x/week/4weeks). After the 4th inhalation, GP were treated with montelukast or dexamethasone. After 72 hours of the 7th inhalation, GP were anesthetised, and lungs were removed and submitted to histopathological evaluation. Results. Montelukast and dexamethasone treatments reduced the number of eosinophils in airway wall and distal lung parenchyma compared to OVA group (P < 0.05). On distal parenchyma, both treatments were effective in reducing RANTES, NF-κB, and fibronectin positive cells compared to OVA group (P < 0.001). Montelukast was more effective in reducing eotaxin positive cells on distal parenchyma compared to dexamethasone treatment (P < 0.001), while there was a more expressive reduction of IGF-I positive cells in OVA-D group (P < 0.001). On airway walls, montelukast and dexamethasone were effective in reducing IGF-I, RANTES, and fibronectin positive cells compared to OVA group (P < 0.05). Dexamethasone was more effective in reducing the number of eotaxin and NF-κB positive cells than Montelukast (P < 0.05). Conclusions. In this animal model, both treatments were effective in modulating allergic inflammation and remodeling distal lung parenchyma and airway wall, contributing to a better control of the inflammatory response. PMID:24151607

  16. Anemia of Chronic Disease and Iron Deficiency Anemia in Inflammatory Bowel Diseases: Pathophysiology, Diagnosis, and Treatment.

    PubMed

    Murawska, Natalia; Fabisiak, Adam; Fichna, Jakub

    2016-05-01

    Anemia coexists with inflammatory bowel disease (IBD) in up to two-thirds of patients, significantly impairing quality of life. The most common types of anemia in patients with IBD are iron deficiency anemia and anemia of chronic disease, which often overlap. In most cases, available laboratory tests allow successful diagnosis of iron deficiency, where difficulties appear, recently established indices such as soluble transferrin-ferritin ratio or percentage of hypochromic red cells are used. In this review, we discuss the management of the most common types of anemia in respect of the latest available data. Thus, we provide the mechanisms underlying pathophysiology of these entities; furthermore, we discuss the role of hepcidin in developing anemia in IBD. Next, we present the treatment options for each type of anemia and highlight the importance of individual choice of action. We also focus on newly developed intravenous iron preparations and novel, promising drug candidates targeting hepcidin. Concurrently, we talk about difficulties in differentiating between the true and functional iron deficiency, and discuss tools facilitating the process. Finally, we emphasize the importance of proper diagnosis and treatment of anemia in IBD. We conclude that management of anemia in patients with IBD is tricky, and appropriate screening of patients regarding anemia is substantial. PMID:26818422

  17. Natural Products as Tools for Defining How Cellular Metabolism Influences Cellular Immune and Inflammatory Function during Chronic Infection

    PubMed Central

    Lovelace, Erica S.; Polyak, Stephen J.

    2015-01-01

    Chronic viral infections like those caused by hepatitis C virus (HCV) and human immunodeficiency virus (HIV) cause disease that establishes an ongoing state of chronic inflammation. While there have been tremendous improvements towards curing HCV with directly acting antiviral agents (DAA) and keeping HIV viral loads below detection with antiretroviral therapy (ART), there is still a need to control inflammation in these diseases. Recent studies indicate that many natural products like curcumin, resveratrol and silymarin alter cellular metabolism and signal transduction pathways via enzymes such as adenosine monophosphate kinase (AMPK) and mechanistic target of rapamycin (mTOR), and these pathways directly influence cellular inflammatory status (such as NF-κB) and immune function. Natural products represent a vast toolkit to dissect and define how cellular metabolism controls cellular immune and inflammatory function. PMID:26633463

  18. Association of terpinolene and diclofenac presents antinociceptive and anti-inflammatory synergistic effects in a model of chronic inflammation

    PubMed Central

    Macedo, E.M.A.; Santos, W.C.; Sousa, B.P.; Lopes, E.M.; Piauilino, C.A.; Cunha, F.V.M.; Sousa, D.P.; Oliveira, F.A.; Almeida, F.R.C.

    2016-01-01

    Pharmacological treatment of inflammatory pain is usually done by administration of non-steroidal anti-inflammatory drugs (NSAIDs). These drugs present high efficacy, although side effects are common, especially gastrointestinal lesions. One of the pharmacological strategies to minimize such effects is the combination of drugs and natural products with synergistic analgesic effect. The monoterpene terpinolene (TPL) is a chemical constituent of essential oils present in many plant species, which have pharmacological activities, such as analgesic and anti-inflammatory. The association of ineffective doses of TPL and diclofenac (DCF) (3.125 and 1.25 mg/kg po, respectively) presented antinociceptive and anti-inflammatory effects in the acute (0, 1, 2, 3, 4, 5 and 6 h, after treatment) and chronic (10 days) inflammatory hyperalgesia induced by Freund's complete adjuvant (CFA) in the right hind paw of female Wistar rats (170-230 g, n=6-8). The mechanical hyperalgesia was assessed by the Randall Selitto paw pressure test, which determines the paw withdrawal thresholds. The development of edema was quantified by measuring the volume of the hind paw by plethismography. The TPL/DCF association reduced neutrophils, macrophages and lymphocytes in the histological analysis of the paw, following a standard staining protocol with hematoxylin and eosin and the counts were performed with the aid of optical microscopy after chronic oral administration of these drugs. Moreover, the TPL/DCF association did not induce macroscopic gastric lesions. A possible mechanism of action of the analgesic effect is the involvement of 5-HT2A serotonin receptors, because ketanserin completely reversed the antinociceptive effect of the TPL/DCF association. These results suggest that the TPL/DCF association had a synergistic anti-inflammatory and analgesic effect without causing apparent gastric injury, and that the serotonergic system may be involved in the antinociceptive effect of this association

  19. Steroids for chronic inflammatory demyelinating polyradiculoneuropathy: evidence base and clinical practice.

    PubMed

    Press, R; Hiew, F L; Rajabally, Y A

    2016-04-01

    Evidence-based therapies for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) consist of corticosteroids, intravenous immunglobulins (IVIg), and plasma exchange. Steroids represent the oldest treatment used historically. In countries where readily available and affordable, IVIg tends to be favored as first-line treatment. The reason for this preference, despite substantially higher costs, is the perception that IVIg is more efficacious and safer than corticosteroids. However, the unselected use of IVIg as a first-line treatment option in all cases of CIDP raises issues of cost-effectiveness in the long-term. Furthermore, serious although rare, particularly thromboembolic side effects may result from their use. Recent data from randomized trials suggest pulsed corticosteroids to have a higher potential in achieving therapy-free remission or longer remission-free periods compared with IVIg, as well as relatively low rates of serious side effects when given as pulsed intravenous infusions during short periods of time. These specific advantages suggest that pulsed steroids could in many cases be used, as the first, rather than second choice of treatment when initiating immunomodulation in CIDP, primarily in hopes of achieving a remission after the short-term use. This article reviews the evidence base for the use of corticosteroids in its various forms in CIDP and factors that may influence clinicians' choice between IVIg and pulsed steroid treatment. The issue of efficacy, relapse rate and time, and side effect profile are analyzed, and some aspects from the authors' experience are discussed in relation to the possibility of using the steroid option as first-line therapy in a large proportion of patients with CIDP. PMID:26437234

  20. Zinc status and its relation to growth retardation in children with chronic inflammatory bowel disease.

    PubMed

    Nishi, Y; Lifshitz, F; Bayne, M A; Daum, F; Silverberg, M; Aiges, H

    1980-12-01

    Zinc status was studied in 30 patients with chronic inflammatory bowel disease (CIBD) as well as in 17 normal children, 13 primordial short stature, and 17 anorexia nervosa patients. Basal serum and urinary excretion levels of zinc were measured in all patients. In addition, a zinc loading test was performed in 16 CIBD patients, 21 normal and/or short stature children, and nine patients with anorexia nervosa. Eleven of 30 patients with CIBD had serum zinc values less than 0.7 microgram/ml, whereas none of the other patients had hypozincemia. In addition, the mean urinary zinc excretion of CIBD patients was significantly lower than that of patients with primordial short stature and with anorexia nervosa. An altered response to oral zinc load was the most frequent abnormality in CIBD patients. Those with moderate and severe clinical disease activity had a decreased serum rise of zinc after the oral load of this ion. Urinary excretion of zinc after oral load was also marked by deficiency in all CIBD patients. The abnormalities of zinc metabolism were more frequent among the CIBD patients with growth abnormalities, although they were also found in patients who had normal growth. Among the 14 patients with CIBD and growth abnormalities, seven were hypozincemic and four hypozincuric. Hypozincemia was only found in four patients who had normal height; however, the growth velocity was not known. The zinc tolerance test revealed abnormalities in four of five CIBD patients with short stature and in two of three patients with slow growth. On the other hand, similar alterations in zinc tolerance tests were seen in three of seven CIBD patients with normal height and growth. PMID:7435430

  1. Dysregulated stress signal sensitivity and inflammatory disinhibition as a pathophysiological mechanism of stress-related chronic fatigue.

    PubMed

    Strahler, Jana; Skoluda, Nadine; Rohleder, Nicolas; Nater, Urs M

    2016-09-01

    Chronic stress and its subsequent effects on biological stress systems have long been recognized as predisposing and perpetuating factors in chronic fatigue, although the exact mechanisms are far from being completely understood. In this review, we propose that sensitivity of immune cells to glucocorticoids (GCs) and catecholamines (CATs) may be the missing link in elucidating how stress turns into chronic fatigue. We searched for in vitro studies investigating the impact of GCs or CATs on mitogen-stimulated immune cells in chronically stressed or fatigued populations, with 34 original studies fulfilling our inclusion criteria. Besides mixed cross-sectional findings for stress- and fatigue-related changes of GC sensitivity under basal conditions or acute stress, longitudinal studies indicate a decrease with ongoing stress. Research on CATs is still scarce, but initial findings point towards a reduction of CAT sensitivity under chronic stress. In the long run, resistance of immune cells to stress signals under conditions of chronic stress might translate into self-maintaining inflammation and inflammatory disinhibition under acute stress, which in turn lead to fatigue. PMID:27208412

  2. Insulin resistance, selfish brain, and selfish immune system: an evolutionarily positively selected program used in chronic inflammatory diseases

    PubMed Central

    2014-01-01

    Insulin resistance (IR) is a general phenomenon of many physiological states, disease states, and diseases. IR has been described in diabetes mellitus, obesity, infection, sepsis, trauma, painful states such as postoperative pain and migraine, schizophrenia, major depression, chronic mental stress, and others. In arthritis, abnormalities of glucose homeostasis were described in 1920; and in 1950 combined glucose and insulin tests unmistakably demonstrated IR. The phenomenon is now described in rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, polymyalgia rheumatica, and others. In chronic inflammatory diseases, cytokine-neutralizing strategies normalize insulin sensitivity. This paper delineates that IR is either based on inflammatory factors (activation of the immune/ repair system) or on the brain (mental activation via stress axes). Due to the selfishness of the immune system and the selfishness of the brain, both can induce IR independent of each other. Consequently, the immune system can block the brain (for example, by sickness behavior) and the brain can block the immune system (for example, stress-induced immune system alterations). Based on considerations of evolutionary medicine, it is discussed that obesity per se is not a disease. Obesity-related IR depends on provoking factors from either the immune system or the brain. Chronic inflammation and/or stress axis activation are thus needed for obesity-related IR. Due to redundant pathways in stimulating IR, a simple one factor-neutralizing strategy might help in chronic inflammatory diseases (inflammation is the key), but not in obesity-related IR. The new considerations towards IR are interrelated to the published theories of IR (thrifty genotype, thrifty phenotype, and others). PMID:25608958

  3. Chronic Inhibition of PDE5 Limits Pro-Inflammatory Monocyte-Macrophage Polarization in Streptozotocin-Induced Diabetic Mice

    PubMed Central

    Venneri, Mary Anna; Giannetta, Elisa; Panio, Giuseppe; De Gaetano, Rita; Gianfrilli, Daniele; Pofi, Riccardo; Masciarelli, Silvia; Fazi, Francesco; Pellegrini, Manuela; Lenzi, Andrea; Naro, Fabio; Isidori, Andrea M.

    2015-01-01

    Diabetes mellitus is characterized by changes in endothelial cells that alter monocyte recruitment, increase classic (M1-type) tissue macrophage infiltration and lead to self-sustained inflammation. Our and other groups recently showed that chronic inhibition of phosphodiesterase-5 (PDE5i) affects circulating cytokine levels in patients with diabetes; whether PDE5i also affects circulating monocytes and tissue inflammatory cell infiltration remains to be established. Using murine streptozotocin (STZ)-induced diabetes and in human vitro cell-cell adhesion models we show that chronic hyperglycemia induces changes in myeloid and endothelial cells that alter monocyte recruitment and lead to self-sustained inflammation. Continuous PDE5i with sildenafil (SILD) expanded tissue anti-inflammatory TIE2-expressing monocytes (TEMs), which are known to limit inflammation and promote tissue repair. Specifically, SILD: 1) normalizes the frequency of circulating pro-inflammatory monocytes triggered by hyperglycemia (53.7 ± 7.9% of CD11b+Gr-1+ cells in STZ vs. 30.4 ± 8.3% in STZ+SILD and 27.1 ± 1.6% in CTRL, P<0.01); 2) prevents STZ-induced tissue inflammatory infiltration (4-fold increase in F4/80+ macrophages in diabetic vs. control mice) by increasing renal and heart anti-inflammatory TEMs (30.9 ± 3.6% in STZ+SILD vs. 6.9 ± 2.7% in STZ, P <0.01, and 11.6 ± 2.9% in CTRL mice); 3) reduces vascular inflammatory proteins (iNOS, COX2, VCAM-1) promoting tissue protection; 4) lowers monocyte adhesion to human endothelial cells in vitro through the TIE2 receptor. All these changes occurred independently from changes of glycemic status. In summary, we demonstrate that circulating renal and cardiac TEMs are defective in chronic hyperglycemia and that SILD normalizes their levels by facilitating the shift from classic (M1-like) to alternative (M2-like)/TEM macrophage polarization. Restoration of tissue TEMs with PDE5i could represent an additional pharmacological tool to prevent end

  4. Chronic Trigeminal Nerve Stimulation Protects Against Seizures, Cognitive Impairments, Hippocampal Apoptosis, and Inflammatory Responses in Epileptic Rats.

    PubMed

    Wang, Qian-Qian; Zhu, Li-Jun; Wang, Xian-Hong; Zuo, Jian; He, Hui-Yan; Tian, Miao-Miao; Wang, Lei; Liang, Gui-Ling; Wang, Yu

    2016-05-01

    Trigeminal nerve stimulation (TNS) has recently been demonstrated effective in the treatment of epilepsy and mood disorders. Here, we aim to determine the effects of TNS on epileptogenesis, cognitive function, and the associated hippocampal apoptosis and inflammatory responses. Rats were injected with pilocarpine to produce status epilepticus (SE) and the following chronic epilepsy. After SE induction, TNS treatment was conducted for 4 consecutive weeks. A pilocarpine re-injection was then used to induce a seizure in the epileptic rats. The hippocampal neuronal apoptosis induced by seizure was assessed by TUNEL staining and inflammatory responses by immunohistochemistry and enzyme-linked immunosorbent assay (ELISA). The spontaneous recurrent seizure (SRS) number was counted through video monitoring, and the cognitive function assessed through Morris Water Maze (MWM) test. TNS treatment attenuated the SRS attacks and improved the cognitive impairment in epileptic rats. A pilocarpine re-injection resulted in less hippocampal neuronal apoptosis and reduced level of interleukin-1 beta (IL-1β), tumor necrosis factor-α (TNF-α), and microglial activation in epileptic rats with TNS treatment in comparison to the epileptic rats without TNS treatment. It is concluded that TNS treatment shortly after SE not only protected against the chronic spontaneous seizures but also improved cognitive impairments. These antiepileptic properties of TNS may be related to its attenuating effects on hippocampal apoptosis and pro-inflammatory responses. PMID:26973056

  5. An inhibitor of neuronal exocytosis (DD04107) displays long-lasting in vivo activity against chronic inflammatory and neuropathic pain.

    PubMed

    Ponsati, Berta; Carreño, Cristina; Curto-Reyes, Verdad; Valenzuela, Belen; Duart, María José; Van den Nest, Wim; Cauli, Omar; Beltran, Beatriz; Fernandez, Jimena; Borsini, Franco; Caprioli, Antonio; Di Serio, Stefano; Veretchy, Mario; Baamonde, Ana; Menendez, Luis; Barros, Francisco; de la Pena, Pilar; Borges, Ricardo; Felipo, Vicente; Planells-Cases, Rosa; Ferrer-Montiel, Antonio

    2012-06-01

    Small peptides patterned after the N terminus of the synaptosomal protein of 25 kDa, a member of the protein complex implicated in Ca(2+)-dependent neuronal exocytosis, inhibit in vitro the release of neuromodulators involved in pain signaling, suggesting an in vivo analgesic activity. Here, we report that compound DD04107 (palmitoyl-EEMQRR-NH(2)), a 6-mer palmitoylated peptide that blocks the inflammatory recruitment of ion channels to the plasma membrane of nociceptors and the release of calcitonin gene-related peptide from primary sensory neurons, displays potent and long-lasting in vivo antihyperalgesia and antiallodynia in chronic models of inflammatory and neuropathic pain, such as the complete Freund's adjuvant, osteosarcoma, chemotherapy, and diabetic neuropathic models. Subcutaneous administration of the peptide produced a dose-dependent antihyperalgesic and antiallodynic activity that lasted ≥24 h. The compound showed a systemic distribution, characterized by a bicompartmental pharmacokinetic profile. Safety pharmacology studies indicated that the peptide is largely devoid of side effects and substantiated that the in vivo activity is not caused by locomotor impairment. Therefore, DD04107 is a potent and long-lasting antinociceptive compound that displays a safe pharmacological profile. These findings support the notion that neuronal exocytosis of receptors and neuronal algogens pivotally contribute to chronic inflammatory and neuropathic pain and imply a central role of peptidergic nociceptor sensitization to the pathogenesis of pain. PMID:22393248

  6. Anti-inflammatory effect of a novel food Cordyceps guangdongensis on experimental rats with chronic bronchitis induced by tobacco smoking.

    PubMed

    Yan, Wenjuan; Li, Taihui; Zhong, Zhiyong

    2014-10-01

    Cordyceps guangdongensis T. H. Li, Q. Y. Lin & B. Song (Cordycipitaceae) is a novel food approved by the Ministry of Public Health of China in 2013. Preliminary studies revealed that this novel food has multiple pharmacological activities such as anti-fatigue effect, antioxidant ability, prolonging life, anti-avian influenza virus activity, and therapeutic effect on chronic renal failure. However, the anti-inflammatory effect on chronic bronchitis and the effective constituent are still unknown. The purpose of this study was to investigate both the anti-inflammatory effect of the edible fungus on experimental rats with chronic bronchitis induced by tobacco smoking, and the pilot effective constituent. Test rats were intragastrically administered with 3 doses of hot-water extract from C. guangdongensis (0.325, 0.65 and 1.30 g kg(-1) bw daily for low, middle and high dose, respectively) for 26 days. Biochemical indices and histological examinations in rats with chronic bronchitis induced by tobacco smoking were determined. The content and molecular weights of the polysaccharide from the hot-water extract were detected by the phenol-sulfuric acid method and gel permeation chromatography, respectively. Biochemical indices in the low, middle and high-dose groups with the hot-water extract of C. guangdongensis were only 53.4%, 46.0% and 40.4% of those in the model control group (total leukocytes), respectively; 70.7%, 60.3% and 58.1% (macrophages); 33.0%, 26.8% and 16.1% (neutrophils); and 22.2%, 23.5% and 13.6% (lymphocytes) of those in the model control group. The bronchial lesions and inflammatory cell infiltration were significantly alleviated in all groups with hot-water extract of C. guangdongensis. This study indicates that the hot-water extract from C. guangdongensis has a significant anti-inflammatory effect on chronic bronchitis. The content of the polysaccharide was 6.92%; the molecular weights of the 3 polysaccharide components were respectively 1.28 × 10

  7. Increased circulating pro-inflammatory cytokines and imbalanced regulatory T-cell cytokines production in chronic idiopathic urticaria.

    PubMed

    Dos Santos, Juliana Cristina; Azor, Mayce Helena; Nojima, Viviane Yoshimi; Lourenço, Francinelson Duarte; Prearo, Erica; Maruta, Celina Wakisaka; Rivitti, Evandro Ararigbóia; da Silva Duarte, Alberto José; Sato, Maria Notomi

    2008-10-01

    The immunologic characterization of chronic idiopathic urticaria (CIU), mainly regarding cytokine profile needs more investigation. We examined circulating inflammatory cytokine levels, T-cell induced secretion, and cytokine mRNA expression in patients with CIU subjected to the intradermal autologous serum skin test (ASST). Increased levels of circulating pro-inflammatory cytokines, such as TNF-alpha, IL-1beta, IL-12p70, and IL-6 have been observed in most of patients with CIU, together with an enhancement of IL-2 secretion following T-cell stimulation. Highlighting the inflammatory profile in CIU found in ASST positive, is the enhanced B-cell proliferative responsiveness and increased IL-17 secretion levels. ASST-positive patients also exhibited impaired IL-4 secretion associated with increased IL-10 production. Altered cytokine expression in patients with ASST-negative, was the down-modulation of spontaneous IL-10 mRNA expression levels in peripheral blood mononuclear cells. Our findings support the concept of immunologic dysregulation in CIU, revealing a systemic inflammatory profile associated with disturbed cytokine production by T cells, mainly related to IL-17 and IL-10 production. PMID:18586117

  8. Differential Features between Chronic Skin Inflammatory Diseases Revealed in Skin-Humanized Psoriasis and Atopic Dermatitis Mouse Models.

    PubMed

    Carretero, Marta; Guerrero-Aspizua, Sara; Illera, Nuria; Galvez, Victoria; Navarro, Manuel; García-García, Francisco; Dopazo, Joaquin; Jorcano, Jose Luis; Larcher, Fernando; del Rio, Marcela

    2016-01-01

    Psoriasis and atopic dermatitis are chronic and relapsing inflammatory diseases of the skin affecting a large number of patients worldwide. Psoriasis is characterized by a T helper type 1 and/or T helper type 17 immunological response, whereas acute atopic dermatitis lesions exhibit T helper type 2-dominant inflammation. Current single gene and signaling pathways-based models of inflammatory skin diseases are incomplete. Previous work allowed us to model psoriasis in skin-humanized mice through proper combinations of inflammatory cell components and disruption of barrier function. Herein, we describe and characterize an animal model for atopic dermatitis using similar bioengineered-based approaches, by intradermal injection of human T helper type 2 lymphocytes in regenerated human skin after partial removal of stratum corneum. In this work, we have extensively compared this model with the previous and an improved version of the psoriasis model, in which T helper type 1 and/or T helper type 17 lymphocytes replace exogenous cytokines. Comparative expression analyses revealed marked differences in specific epidermal proliferation and differentiation markers and immune-related molecules, including antimicrobial peptides. Likewise, the composition of the dermal inflammatory infiltrate presented important differences. The availability of accurate and reliable animal models for these diseases will contribute to the understanding of the pathogenesis and provide valuable tools for drug development and testing. PMID:26763433

  9. Characterization of Inflammatory Response in Acute-on-Chronic Liver Failure and Relationship with Prognosis

    PubMed Central

    Solé, Cristina; Solà, Elsa; Morales-Ruiz, Manuel; Fernàndez, Guerau; Huelin, Patricia; Graupera, Isabel; Moreira, Rebeca; de Prada, Gloria; Ariza, Xavier; Pose, Elisa; Fabrellas, Núria; Kalko, Susana G.; Jiménez, Wladimiro; Ginès, Pere

    2016-01-01

    ACLF is characterized by a systemic inflammatory response, but the cytokines involved in this process have not been well studied. The aim of this study was to characterize the systemic inflammatory response in patients with cirrhosis and ACLF and its relationship with prognosis. Fifty-five patients with cirrhosis, 26 with ACLF, were studied prospectively. Systemic inflammatory response was analyzed by measuring a large array of plasma cytokines by using a multiplex kit. A principal component analysis show noticeable differences between ACLF and decompensated cirrhosis without ACLF. Patients with ACLF had significant abnormal levels of 12 cytokines compared to those without ACLF, including: VCAM-1, VEGF-A, Fractalkine, MIP-1α, Eotaxin, IP-10, RANTES, GM-CSF, IL-1β, IL-2, ICAM-1, and MCP-1. Cytokines showing the most marked relationship with ACLF were VCAM-1 and VEGF-A (AUCROC 0.77; p = 0.001). There was a significant relationship between some of inflammatory mediators and 3-month mortality, particularly VCAM-1, ICAM-1, and GM-CSF (AUCROC>0.7; p < 0.05). Functional Enrichment Analysis showed that inflammatory markers differentially expressed in ACLF patients were enriched in leukocyte migration, particularly monocytes and macrophages, and chemotaxis pathways. In conclusion, ACLF is characterized by a marked inflammatory reaction with activation of mediators of adhesion and migration of leukocytes. The intensity of the inflammatory reaction correlates with prognosis. PMID:27578545

  10. Characterization of Inflammatory Response in Acute-on-Chronic Liver Failure and Relationship with Prognosis.

    PubMed

    Solé, Cristina; Solà, Elsa; Morales-Ruiz, Manuel; Fernàndez, Guerau; Huelin, Patricia; Graupera, Isabel; Moreira, Rebeca; de Prada, Gloria; Ariza, Xavier; Pose, Elisa; Fabrellas, Núria; Kalko, Susana G; Jiménez, Wladimiro; Ginès, Pere

    2016-01-01

    ACLF is characterized by a systemic inflammatory response, but the cytokines involved in this process have not been well studied. The aim of this study was to characterize the systemic inflammatory response in patients with cirrhosis and ACLF and its relationship with prognosis. Fifty-five patients with cirrhosis, 26 with ACLF, were studied prospectively. Systemic inflammatory response was analyzed by measuring a large array of plasma cytokines by using a multiplex kit. A principal component analysis show noticeable differences between ACLF and decompensated cirrhosis without ACLF. Patients with ACLF had significant abnormal levels of 12 cytokines compared to those without ACLF, including: VCAM-1, VEGF-A, Fractalkine, MIP-1α, Eotaxin, IP-10, RANTES, GM-CSF, IL-1β, IL-2, ICAM-1, and MCP-1. Cytokines showing the most marked relationship with ACLF were VCAM-1 and VEGF-A (AUCROC 0.77; p = 0.001). There was a significant relationship between some of inflammatory mediators and 3-month mortality, particularly VCAM-1, ICAM-1, and GM-CSF (AUCROC>0.7; p < 0.05). Functional Enrichment Analysis showed that inflammatory markers differentially expressed in ACLF patients were enriched in leukocyte migration, particularly monocytes and macrophages, and chemotaxis pathways. In conclusion, ACLF is characterized by a marked inflammatory reaction with activation of mediators of adhesion and migration of leukocytes. The intensity of the inflammatory reaction correlates with prognosis. PMID:27578545

  11. [VASCULAR ENDOTHELIAL GROWTH FACTOR AND SOME INDICATORS OF ENDOTHELIAL DYSFUNCTION OF PATIENTS HAVING CHRONIC INFLAMMATORY DISEASES OF THE GASTRO DUODENAL ZONE].

    PubMed

    Zavyalova, O V; Spivakovskiy, Yu M; Tchernenkov, Yu V; Lukina, O A

    2015-01-01

    The aim of the study was to determine the content of vaskuloendotelian growth factor and nitric oxide in children with chronic inflammatory diseases of the stomach and duodenum. The study involved 63 children with chronic inflammatory diseases of the gastroduodenal zone. Substrate study was serum. The data obtained were compared with a group of healthy children. The highest possible content vaskuloendotelian growth factor noted in the group of children with duodenal ulcer in the acute phase and in the group of chronic gastroduodenita associated with Helicobacter pylori. According to the results of the study established the role of nitric oxide and vaskuloendotelian growth factor in the pathogenesis of gastroduodenal diseases. PMID:26415264

  12. Adipose Tissue Is a Neglected Viral Reservoir and an Inflammatory Site during Chronic HIV and SIV Infection

    PubMed Central

    Damouche, Abderaouf; Huot, Nicolas; Dejucq-Rainsford, Nathalie; Satie, Anne-Pascale; Mélard, Adeline; David, Ludivine; Gommet, Céline; Ghosn, Jade; Noel, Nicolas; Pourcher, Guillaume; Martinez, Valérie; Benoist, Stéphane; Béréziat, Véronique; Cosma, Antonio; Favier, Benoit; Vaslin, Bruno; Rouzioux, Christine; Capeau, Jacqueline; Müller-Trutwin, Michaela; Dereuddre-Bosquet, Nathalie; Le Grand, Roger; Lambotte, Olivier; Bourgeois, Christine

    2015-01-01

    Two of the crucial aspects of human immunodeficiency virus (HIV) infection are (i) viral persistence in reservoirs (precluding viral eradication) and (ii) chronic inflammation (directly associated with all-cause morbidities in antiretroviral therapy (ART)-controlled HIV-infected patients). The objective of the present study was to assess the potential involvement of adipose tissue in these two aspects. Adipose tissue is composed of adipocytes and the stromal vascular fraction (SVF); the latter comprises immune cells such as CD4+ T cells and macrophages (both of which are important target cells for HIV). The inflammatory potential of adipose tissue has been extensively described in the context of obesity. During HIV infection, the inflammatory profile of adipose tissue has been revealed by the occurrence of lipodystrophies (primarily related to ART). Data on the impact of HIV on the SVF (especially in individuals not receiving ART) are scarce. We first analyzed the impact of simian immunodeficiency virus (SIV) infection on abdominal subcutaneous and visceral adipose tissues in SIVmac251 infected macaques and found that both adipocytes and adipose tissue immune cells were affected. The adipocyte density was elevated, and adipose tissue immune cells presented enhanced immune activation and/or inflammatory profiles. We detected cell-associated SIV DNA and RNA in the SVF and in sorted CD4+ T cells and macrophages from adipose tissue. We demonstrated that SVF cells (including CD4+ T cells) are infected in ART-controlled HIV-infected patients. Importantly, the production of HIV RNA was detected by in situ hybridization, and after the in vitro reactivation of sorted CD4+ T cells from adipose tissue. We thus identified adipose tissue as a crucial cofactor in both viral persistence and chronic immune activation/inflammation during HIV infection. These observations open up new therapeutic strategies for limiting the size of the viral reservoir and decreasing low-grade chronic

  13. Investigating the Burden of Chronic Pain: An Inflammatory and Metabolic Composite

    PubMed Central

    Sibille, Kimberly T.; Steingrímsdóttir, Ólöf A.; Fillingim, Roger B.; Stubhaug, Audun; Schirmer, Henrik; Chen, Huaihou; McEwen, Bruce S.; Nielsen, Christopher S.

    2016-01-01

    Background. Chronic pain is associated with increased morbidity and mortality, predominated by cardiovascular disease and cancer. Investigating related risk factor measures may elucidate the biological burden of chronic pain. Objectives. We hypothesized that chronic pain severity would be positively associated with the risk factor composite. Methods. Data from 12,982 participants in the 6th Tromsø study were analyzed. Questionnaires included demographics, health behaviors, medical comorbidities, and chronic pain symptoms. The risk factor composite was comprised of body mass index, fibrinogen, C-reactive protein, and triglycerides. Chronic pain severity was characterized by frequency, intensity, time/duration, and total number of pain sites. Results. Individuals with chronic pain had a greater risk factor composite than individuals without chronic pain controlling for covariates and after excluding inflammation-related health conditions (p < 0.001). A significant “dose-response” relationship was demonstrated with pain severity (p < 0.001). In individuals with chronic pain, the risk factor composite varied by health behavior, exercise, lower levels and smoking, and higher levels. Discussion. The risk factor composite was higher in individuals with chronic pain, greater with increasing pain severity, and influenced by health behaviors. Conclusions. Identification of a biological composite sensitive to pain severity and adaptive/maladaptive behaviors would have significant clinical and research utility. PMID:27445627

  14. Investigating the Burden of Chronic Pain: An Inflammatory and Metabolic Composite.

    PubMed

    Sibille, Kimberly T; Steingrímsdóttir, Ólöf A; Fillingim, Roger B; Stubhaug, Audun; Schirmer, Henrik; Chen, Huaihou; McEwen, Bruce S; Nielsen, Christopher S

    2016-01-01

    Background. Chronic pain is associated with increased morbidity and mortality, predominated by cardiovascular disease and cancer. Investigating related risk factor measures may elucidate the biological burden of chronic pain. Objectives. We hypothesized that chronic pain severity would be positively associated with the risk factor composite. Methods. Data from 12,982 participants in the 6th Tromsø study were analyzed. Questionnaires included demographics, health behaviors, medical comorbidities, and chronic pain symptoms. The risk factor composite was comprised of body mass index, fibrinogen, C-reactive protein, and triglycerides. Chronic pain severity was characterized by frequency, intensity, time/duration, and total number of pain sites. Results. Individuals with chronic pain had a greater risk factor composite than individuals without chronic pain controlling for covariates and after excluding inflammation-related health conditions (p < 0.001). A significant "dose-response" relationship was demonstrated with pain severity (p < 0.001). In individuals with chronic pain, the risk factor composite varied by health behavior, exercise, lower levels and smoking, and higher levels. Discussion. The risk factor composite was higher in individuals with chronic pain, greater with increasing pain severity, and influenced by health behaviors. Conclusions. Identification of a biological composite sensitive to pain severity and adaptive/maladaptive behaviors would have significant clinical and research utility. PMID:27445627

  15. Challenges and Current Efforts in the Development of Biomarkers for Chronic Inflammatory and Remodeling Conditions of the Lungs.

    PubMed

    Grunig, Gabriele; Baghdassarian, Aram; Park, Sung-Hyun; Pylawka, Serhiy; Bleck, Bertram; Reibman, Joan; Berman-Rosenzweig, Erika; Durmus, Nedim

    2015-01-01

    This review discusses biomarkers that are being researched for their usefulness to phenotype chronic inflammatory lung diseases that cause remodeling of the lung's architecture. The review focuses on asthma, chronic obstructive pulmonary disease (COPD), and pulmonary hypertension. Bio-markers of environmental exposure and specific classes of biomarkers (noncoding RNA, metabolism, vitamin, coagulation, and microbiome related) are also discussed. Examples of biomarkers that are in clinical use, biomarkers that are under development, and biomarkers that are still in the research phase are discussed. We chose to present examples of the research in biomarker development by diseases, because asthma, COPD, and pulmonary hypertension are distinct entities, although they clearly share processes of inflammation and remodeling. PMID:26917944

  16. Challenges and Current Efforts in the Development of Biomarkers for Chronic Inflammatory and Remodeling Conditions of the Lungs

    PubMed Central

    Grunig, Gabriele; Baghdassarian, Aram; Park, Sung-Hyun; Pylawka, Serhiy; Bleck, Bertram; Reibman, Joan; Berman-Rosenzweig, Erika; Durmus, Nedim

    2015-01-01

    This review discusses biomarkers that are being researched for their usefulness to phenotype chronic inflammatory lung diseases that cause remodeling of the lung’s architecture. The review focuses on asthma, chronic obstructive pulmonary disease (COPD), and pulmonary hypertension. Bio-markers of environmental exposure and specific classes of biomarkers (noncoding RNA, metabolism, vitamin, coagulation, and microbiome related) are also discussed. Examples of biomarkers that are in clinical use, biomarkers that are under development, and biomarkers that are still in the research phase are discussed. We chose to present examples of the research in biomarker development by diseases, because asthma, COPD, and pulmonary hypertension are distinct entities, although they clearly share processes of inflammation and remodeling. PMID:26917944

  17. The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain.

    PubMed

    Younger, Jarred; Parkitny, Luke; McLain, David

    2014-04-01

    Low-dose naltrexone (LDN) has been demonstrated to reduce symptom severity in conditions such as fibromyalgia, Crohn's disease, multiple sclerosis, and complex regional pain syndrome. We review the evidence that LDN may operate as a novel anti-inflammatory agent in the central nervous system, via action on microglial cells. These effects may be unique to low dosages of naltrexone and appear to be entirely independent from naltrexone's better-known activity on opioid receptors. As a daily oral therapy, LDN is inexpensive and well-tolerated. Despite initial promise of efficacy, the use of LDN for chronic disorders is still highly experimental. Published trials have low sample sizes, and few replications have been performed. We cover the typical usage of LDN in clinical trials, caveats to using the medication, and recommendations for future research and clinical work. LDN may represent one of the first glial cell modulators to be used for the management of chronic pain disorders. PMID:24526250

  18. Assessment of Inflammation in an Acute on Chronic Model of Inflammatory Bowel Disease with Ultrasound Molecular Imaging

    PubMed Central

    Machtaler, Steven; Knieling, Ferdinand; Luong, Richard; Tian, Lu; Willmann, Jürgen K.

    2015-01-01

    Background: Ultrasound (US) molecular imaging has shown promise in assessing inflammation in preclinical, murine models of inflammatory bowel disease. These models, however, initiated acute inflammation on previously normal colons, in contrast to patients where acute exacerbations are often in chronically inflamed regions. In this study, we explored the potential of dual P- and E-selectin targeted US imaging for assessing acute inflammation on a murine quiescent chronic inflammatory background. Methods: Chronic colitis was induced using three cycles of 4% DSS in male FVB mice. Acute inflammation was initiated 2 weeks after the final DSS cycle through rectal administration of 1% TNBS. Mice at different stages of inflammation were imaged using a small animal ultrasound system following i.v. injection of microbubbles targeted to P- and E-selectin. In vivo imaging results were correlated with ex vivo immunofluorescence and histology. Results: Induction of acute inflammation resulted in an increase in the targeted US signal from 5.5 ± 5.1 arbitrary units (a.u.) at day 0 to 61.0 ± 45.2 a.u. (P < 0.0001) at day 1, 36.3 ± 33.1 a.u. at day 3, returning to levels similar to control at day 5. Immunofluorescence showed significant increase in the percentage of P- and E-selectin positive vessels at day 1 (P-selectin: 21.0 ± 7.1% of vessels; P < 0.05; E-selectin: 16.4 ±3.7%; P < 0.05) compared to day 0 (P-selectin: 10.3 ± 5.7%; E-selectin: 7.3 ± 7.0%). Conclusions: Acute inflammation can be accurately measured in a clinically relevant murine model of chronic IBD using ultrasound molecular imaging with a dual P- and E- selectin-targeted contrast agent. PMID:26379784

  19. Divergent Inflammatory, Fibrogenic, and Liver Progenitor Cell Dynamics in Two Common Mouse Models of Chronic Liver Injury.

    PubMed

    Köhn-Gaone, Julia; Dwyer, Benjamin J; Grzelak, Candice A; Miller, Gregory; Shackel, Nicholas A; Ramm, Grant A; McCaughan, Geoffrey W; Elsegood, Caryn L; Olynyk, John K; Tirnitz-Parker, Janina E E

    2016-07-01

    Complications of end-stage chronic liver disease signify a major cause of mortality worldwide. Irrespective of the underlying cause, most chronic liver diseases are characterized by hepatocellular necrosis, inflammation, fibrosis, and proliferation of liver progenitor cells or ductular reactions. Vast differences exist between experimental models that mimic these processes, and their identification is fundamental for translational research. We compared two common murine models of chronic liver disease: the choline-deficient, ethionine-supplemented (CDE) diet versus thioacetamide (TAA) supplementation. Markers of liver injury, including serum alanine transaminase levels, apoptosis, hepatic fat loading, and oxidative stress, as well as inflammatory, fibrogenic and liver progenitor cell responses, were assessed at days 3, 7, 14, 21, and 42. This study revealed remarkable differences between the models. It identified periportal injury and fibrosis with an early peak and slow normalization of all parameters in the CDE regimen, whereas TAA-treated mice had pericentral patterns of progressive injury and fibrosis, resulting in a more severe hepatic injury phenotype. This study is the first to resolve two different patterns of injury and fibrosis in the CDE and TAA model and to indisputably identify the fibrosis pattern in the TAA model as driven from the pericentral vein region. Our data provide a valuable foundation for future work using the CDE and TAA regimens to model a variety of human chronic liver diseases. PMID:27181403

  20. Electron-autoradiographic study of the wall of the large bronchi in chronic inflammatory lung disease

    SciTech Connect

    Nepomnyashchikh, G.I.; Efremov, V.N.; Tumanov, V.P.

    1986-04-01

    This paper studies chronic bronchitis from the standpoint of parenchymatous-stromal interrelations, using light and electron-microscopic autoradiography. Pieces of the walls of the lobar and segmental bronchi, obtained by incision during bronchoscopy on 19 patients with chronic imflammatory lung disease were studied. From the sample of tissue obtained fragments were incubated in medium no. 199, containing either tritium-thymidine, tritium-uridine, or tritium-proline. The results of the studies present a more complete idea of the morphogenesis of chronic sclerotic changes in the human bronchii.

  1. Deletion of macrophage migration inhibitory factor inhibits murine oral carcinogenesis: Potential role for chronic pro-inflammatory immune mediators.

    PubMed

    Oghumu, Steve; Knobloch, Thomas J; Terrazas, Cesar; Varikuti, Sanjay; Ahn-Jarvis, Jennifer; Bollinger, Claire E; Iwenofu, Hans; Weghorst, Christopher M; Satoskar, Abhay R

    2016-09-15

    Oral cancer kills about 1 person every hour each day in the United States and is the sixth most prevalent cancer worldwide. The pro-inflammatory cytokine 'macrophage migration inhibitory factor' (MIF) has been shown to be expressed in oral cancer patients, yet its precise role in oral carcinogenesis is not clear. In this study, we examined the impact of global Mif deletion on the cellular and molecular process occurring during oral carcinogenesis using a well-established mouse model of oral cancer with the carcinogen 4-nitroquinoline-1-oxide (4NQO). C57BL/6 Wild-type (WT) and Mif knock-out mice were administered with 4NQO in drinking water for 16 weeks, then regular drinking water for 8 weeks. Mif knock-out mice displayed fewer oral tumor incidence and multiplicity, accompanied by a significant reduction in the expression of pro-inflammatory cytokines Il-1β, Tnf-α, chemokines Cxcl1, Cxcl6 and Ccl3 and other molecular biomarkers of oral carcinogenesis Mmp1 and Ptgs2. Further, systemic accumulation of myeloid-derived tumor promoting immune cells was inhibited in Mif knock-out mice. Our results demonstrate that genetic Mif deletion reduces the incidence and severity of oral carcinogenesis, by inhibiting the expression of chronic pro-inflammatory immune mediators. Thus, targeting MIF is a promising strategy for the prevention or therapy of oral cancer. PMID:27164411

  2. Wu-Tou Decoction Inhibits Chronic Inflammatory Pain in Mice: Participation of TRPV1 and TRPA1 Ion Channels

    PubMed Central

    Wang, Chao; Liu, Chunfang; Wan, Hongye; Sun, Danni; Xu, Tengfei; Yang, Yue; Qu, Yakun; Xu, Ying; Jing, Xianghong; Liu, Junling; Chen, Shuping; Liu, Zhiqiang

    2015-01-01

    Wu-tou decoction (WTD) is a classic traditional Chinese medicine formula and has been used effectively to treat joint diseases clinically. Previous reports indicated that WTD possesses anti-inflammatory activity; however, its actions on pain have not been clarified. Here, we investigated the antinociceptive activity of WTD in CFA-induced mice, and its possible mechanism of the action associated with transient receptor potential (TRP) ion channels was also explored. Our results showed that 1.58, 3.15, and 6.30 g/kg WTD significantly attenuated mechanical, cold, and heat hypersensitivities. Moreover, WTD effectively inhibited spontaneous nociceptive responses to intraplantar injections of capsaicin and cinnamaldehyde, respectively. WTD also effectively suppressed jumping and wet-dog-shake behaviors to intraperitoneal injection of icilin. Additionally, WTD significantly reduced protein expression of TRPV1 and TRPA1 in dorsal root ganglia and skins of injured paw. Collectively, our data demonstrate firstly that WTD exerts antinociceptive activity in inflammatory conditions by attenuating mechanical, cold, and heat hypersensitivities. This antinociceptive effect may result in part from inhibiting the activities of TRPV1, TRPA1, and TRPM8, and the suppression of TRPV1 and TRPA1 protein by WTD was also highly effective. These findings suggest that WTD might be an attractive and suitable therapeutic agent for the management of chronic inflammatory pain. PMID:25839032

  3. The Telomere/Telomerase System in Chronic Inflammatory Diseases. Cause or Effect?

    PubMed

    Kordinas, Vasileios; Ioannidis, Anastasios; Chatzipanagiotou, Stylianos

    2016-01-01

    Telomeres are specialized nucleoprotein structures located at the end of linear chromosomes and telomerase is the enzyme responsible for telomere elongation. Telomerase activity is a key component of many cancer cells responsible for rapid cell division but it has also been found by many laboratories around the world that telomere/telomerase biology is dysfunctional in many other chronic conditions as well. These conditions are characterized by chronic inflammation, a situation mostly overlooked by physicians regarding patient treatment. Among others, these conditions include diabetes, renal failure, chronic obstructive pulmonary disease, etc. Since researchers have in many cases identified the association between telomerase and inflammation but there are still many missing links regarding this correlation, the latest findings about this phenomenon will be discussed by reviewing the literature. Our focus will be describing telomere/telomerase status in chronic diseases under the prism of inflammation, reporting molecular findings where available and proposing possible future approaches. PMID:27598205

  4. Comparative effects of dexamethasone and bergenin on chronic bronchitis and their anti-inflammatory mechanisms based on NMR metabolomics.

    PubMed

    Ren, Xiaolei; Ma, Shuangshuang; Wang, Juan; Tian, Simin; Fu, Xiaorui; Liu, Xinfeng; Li, Zhongfeng; Zhao, Baosheng; Wang, Xueyong

    2016-05-24

    In order to compare the effect of dexamethasone and bergenin on chronic bronchitis and to reveal their anti-inflammatory mechanisms, (1)H NMR-based metabolomics was performed to explore the potential biomarkers of the disease and study the therapeutic mechanisms of the drugs. In this study, 40 Sprague-Dawley male rats were randomly divided into 4 groups, namely control, model, dexamethasone and bergenin groups, with 10 rats in each group. Except for the control group, rats from the other three groups were exposed to tobacco smoke for 1 h d(-1) for 28 days. During the modeling, dexamethasone (0.2 mg kg(-1)) and bergenin (87 mg kg(-1)) were administered orally to dexamethasone or bergenin rats 3 h after exposure every day. On the other hand, control and model rats were intragastrically administered water. According to the results of morphometric analysis of the airway epithelium and the count of white blood cells in the bronchoalveolar lavage fluid (BALF), dexamethasone and bergenin could suppress the infiltration of inflammatory cells, inhibit the secretion of mucus, and reduce white blood cells in BALF. Serum samples from the rats' orbits were collected every week. The metabolic profiles of sera were analyzed by multivariate statistical analyses, including PCA, PLS-DA and OPLS-DA models, and 18 metabolites were identified. The dynamic fluctuations of these biomarkers in sera from different groups were detected. The results suggested that the anti-inflammatory mechanism of dexamethasone may be associated with BCAA metabolism and glycolysis while bergenin could change BCAA metabolism, glycine, serine and threonine metabolism, and glycolysis to treat chronic bronchitis. PMID:27098339

  5. A diagnosis challenge-L4 nerve root compression as the initial presentation of chronic inflammatory demyelinating polyneuropathy.

    PubMed

    Cojocaru, Inimioara Mihaela; Alexianu, Marilena; Bastian, Alexandra; Sapira, Violeta; Herţea, Cristina; Cojocaru, M

    2012-01-01

    The authors present the case of a 65-year-old woman who was admitted for paraparesis and paresthesias in the inferior limbs. The neurological examination revealed the difficulty in extension of the right foot and of the right toe, accompanied by paresthesias located in the anterolateral area of the right leg, dorsum and plantar area of the foot, the reduction of the right knee jerk, and of the ankle tendon jerk both sides. The vertebro-spinal MRI showed lumbar canal stenosis with L4 intraforaminal compression on the right, and L2-L3 on the left. CSF examination revealed mild increase in protein concentration. The morphological picture of the sural nerve biopsy was compatible with a chronic inflammatory neuropathy and severe muscular lesions of neurogenic origin were observed on right gastrocnemius muscle biopsy. The diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP) was established. Solu-medrol (0.5 g/d)-5 days, then medrol (prednisolone) was done, followed by improving of the symptomatology. For the relapse of the disease intravenous immunoglobulins (IVIG)-0.4 g/kg/d-5 days was the elective treatment. Six months later she presented a new relapse. IVIG were administered with the remission of the sensitive symptoms. A chronic treatment with medrol was recommended. The diagnosis of L4 disc herniation was obvious in the studied case, but the electroneurographic examination brought extra data for the associated diagnosis of CIDP whose onset was asymmetrical and initially paucisymptomatic. Neither the electroneurographic examination nor the CSF examination were total relevant for CIDP, imposing the sural nerve biopsy. The diagnosis of CIDP involves a team-work composed of neurologist, electroneurophysiologist and neuropathologist. PMID:23610977

  6. Medical rare book provenance.

    PubMed Central

    Overmier, J A; Sentz, L

    1987-01-01

    Provenance is defined as the record of a book's ownership history. Its value and uses are explored. A survey of provenance practices in medical school rare book libraries found that only 21% of the reporting libraries maintain this important file. Examples of the uses and value of a provenance file in a medical rare book collection are presented. Decisions necessary to institute and maintain such a file are outlined and discussed. PMID:3828606

  7. TAM receptor-dependent regulation of SOCS3 and MAPKs contributes to pro-inflammatory cytokine downregulation following chronic NOD2 stimulation of human macrophages1

    PubMed Central

    Zheng, Shasha; Hedl, Matija; Abraham, Clara

    2014-01-01

    Microbial-induced cytokine regulation is critical to intestinal immune homeostasis. Acute stimulation of NOD2, the Crohn’s disease-associated sensor of bacterial peptidoglycan, induces cytokines. However, cytokines are attenuated after chronic NOD2 and pattern recognition receptor (PRR) stimulation of macrophages; similar attenuation is observed in intestinal macrophages. The role of Tyro3, Axl and Mer (TAM) receptors in regulating chronic PRR stimulation and NOD2-induced outcomes has not been examined. Moreover, TAM receptors have been relatively less investigated in human macrophages. Whereas TAM receptors did not downregulate acute NOD2-induced cytokines in primary human macrophages, they were essential for downregulating signaling and pro-inflammatory cytokine secretion after chronic NOD2 and TLR4 stimulation. Axl and Mer were similarly required in mice for cytokine downregulation after chronic NOD2 stimulation in vivo and in intestinal tissues. Consistently, TAM expression was increased in human intestinal myeloid-derived cells. Chronic NOD2 stimulation led to IL-10- and TGFβ-dependent TAM upregulation in human macrophages, which in turn, upregulated SOCS3 expression. Restoring SOCS3 expression under TAM knockdown conditions restored chronic NOD2-mediated pro-inflammatory cytokine downregulation. In contrast to the upregulated pro-inflammatory cytokines, attenuated IL-10 secretion was maintained in TAM-deficient macrophages upon chronic NOD2 stimulation. The level of MAPK activation in TAM-deficient macrophages after chronic NOD2 stimulation was insufficient to upregulate IL-10 secretion; however, full restoration of MAPK activation under these conditions restored c-Fos, c-Jun, MAFK and PU.1 binding to the IL-10 promoter and IL-10 secretion. Therefore, TAM receptors are critical for downregulating pro-inflammatory cytokines under the chronic NOD2 stimulation conditions observed in the intestinal environment. PMID:25567680

  8. Immunomodulatory Device Promotes a Shift of Circulating Monocytes to a Less Inflammatory Phenotype in Chronic Hemodialysis Patients.

    PubMed

    Szamosfalvi, Balazs; Westover, Angela; Buffington, Deborah; Yevzlin, Alexander; Humes, H David

    2016-01-01

    Patients with end-stage renal disease (ESRD) on chronic hemodialysis (HD) suffer accelerated morbidity and mortality rates caused by cardiovascular disease and infections. Chronic inflammation plays a critical role in these poor outcomes. The activated monocyte (MO) has become a prime therapeutic target to modulate this inflammatory process. A selective cytopheretic device (SCD) was evaluated to assess its effects on the circulating MO pool. A pilot trial was undertaken in 15 ESRD patients on HD with C-reactive protein (CRP) levels greater than 5 mg/dl. An excellent safety profile was observed with no decline in leukocyte (LE) or platelet counts. The effect of SCD therapy on MO phenotypes in these patients was determined on peripheral blood MO utilizing flow cytometry. SCD therapy promoted a shift in MO phenotype from predominantly CD14 expressing MO at baseline/pre-SCD therapy to CD14 expressing MO post-SCD therapy. A significant shift in MO population phenotype afforded by a single SCD therapy session was observed (p < 0.013). In a subset of patients (n = 7) presenting with type 2 diabetes mellitus (T2D), this persistent decline in MO CD14 expression was sustained as long as 2 weeks posttherapy. These results demonstrate that the SCD therapy has the potential to modulate the chronic proinflammatory state in ESRD patients. PMID:27258222

  9. The neuroimmune connection interferes with tissue regeneration and chronic inflammatory disease in the skin.

    PubMed

    Peters, Eva M J; Liezmann, Christiane; Klapp, Burghard F; Kruse, Johannes

    2012-07-01

    Research over the past decades has revealed close interactions between the nervous and immune systems that regulate peripheral inflammation and link psychosocial stress with chronic somatic disease. Besides activation of the sympathetic and the hypothalamus-pituitary-adrenal axis, stress leads to increased neurotrophin and neuropeptide production in organs at the self-environment interface. The scope of this short review is to discuss key functions of these stress mediators in the skin, an exemplary stress-targeted and stress-sensitive organ. We will focus on the skin's response to acute and chronic stress in tissue regeneration and pathogenesis of allergic inflammation, psoriasis, and skin cancer to illustrate the impact of local stress-induced neuroimmune interaction on chronic inflammation. PMID:22823443

  10. Otitis media in the Tgif knockout mouse implicates TGFβ signalling in chronic middle ear inflammatory disease

    PubMed Central

    Tateossian, Hilda; Morse, Susan; Parker, Andrew; Mburu, Philomena; Warr, Nick; Acevedo-Arozena, Abraham; Cheeseman, Michael; Wells, Sara; Brown, Steve D.M.

    2013-01-01

    Otitis media with effusion (OME) is the most common cause of hearing loss in children and tympanostomy to alleviate the condition remains the commonest surgical intervention in children in the developed world. Chronic and recurrent forms of OM are known to have a very significant genetic component, however, until recently little was known of the underlying genes involved. The identification of mouse models of chronic OM has indicated a role of transforming growth factor beta (TGFβ) signalling and its impact on responses to hypoxia in the inflamed middle ear. We have, therefore, investigated the role of TGFβ signalling and identified and characterized a new model of chronic OM carrying a mutation in the gene for transforming growth interacting factor 1 (Tgif1). Tgif1 homozygous mutant mice have significantly raised auditory thresholds due to a conductive deafness arising from a chronic effusion starting at around 3 weeks of age. The OM is accompanied by a significant thickening of the middle ear mucosa lining, expansion of mucin-secreting goblet cell populations and raised levels of vascular endothelial growth factor, TNF-α and IL-1β in ear fluids. We also identified downstream effects on TGFβ signalling in middle ear epithelia at the time of development of chronic OM. Both phosphorylated SMAD2 and p21 levels were lowered in the homozygous mutant, demonstrating a suppression of the TGFβ pathway. The identification and characterization of the Tgif mutant supports the role of TGFβ signalling in the development of chronic OM and provides an important candidate gene for genetic studies in the human population. PMID:23459932

  11. Anti-inflammatory effects of simvastatin in patients with chronic heart failure.

    PubMed

    Pinchuk, T V; Fedulaev, Yu N; Khairetdinova, G A; Denisova, N N; Chura, O V; Logunova, I Yu

    2014-09-01

    Proinflammatory markers were evaluated in patients with chronic heart failure of ischemic origin and essential hypertension with preserved left-ventricular ejection fraction before and after a 6-month course of simvastatin therapy (20 mg/day). The study was carried out in 125 patients with diastolic dysfunction manifested as impaired relaxation and pseudonormalization. The main group received standard therapy for chronic heart failure and simvastatin, controls received only standard therapy. In addition, the results in the main group were compared in patients with different types of left-ventricular diastolic dysfunction. Simvastatin therapy significantly reduced the levels of C-reactive protein and IL-6. PMID:25257410

  12. Chronic Psychological Stress Disrupted the Composition of the Murine Colonic Microbiota and Accelerated a Murine Model of Inflammatory Bowel Disease.

    PubMed

    Watanabe, Yohei; Arase, Sohei; Nagaoka, Noriko; Kawai, Mitsuhisa; Matsumoto, Satoshi

    2016-01-01

    The effect of psychological stress on the gastrointestinal microbiota is widely recognized. Chronic psychological stress may be associated with increased disease activity in inflammatory bowel disease, but the relationships among psychological stress, the gastrointestinal microbiota, and the severity of colitis is not yet fully understood. Here, we examined the impact of 12-week repeated water-avoidance stress on the microbiota of two inbred strains of T cell receptor alpha chain gene knockout mouse (background, BALB/c and C57BL/6) by means of next-generation sequencing of bacterial 16S rRNA genes. In both mouse strains, knockout of the T cell receptor alpha chain gene caused a loss of gastrointestinal microbial diversity and stability. Chronic exposure to repeated water-avoidance stress markedly altered the composition of the colonic microbiota of C57BL/6 mice, but not of BALB/c mice. In C57BL/6 mice, the relative abundance of genus Clostridium, some members of which produce the toxin phospholipase C, was increased, which was weakly positively associated with colitis severity, suggesting that expansion of specific populations of indigenous pathogens may be involved in the exacerbation of colitis. However, we also found that colitis was not exacerbated in mice with a relatively diverse microbiota even if their colonic microbiota contained an expanded phospholipase C-producing Clostridium population. Exposure to chronic stress also altered the concentration of free immunoglobulin A in colonic contents, which may be related to both the loss of bacterial diversity in the colonic microbiota and the severity of the colitis exacerbation. Together, these results suggest that long-term exposure to psychological stress induces dysbiosis in the immunodeficient mouse in a strain-specific manner and also that alteration of microbial diversity, which may be related to an altered pattern of immunoglobulin secretion in the gastrointestinal tract, might play a crucial role in the

  13. Chronic Psychological Stress Disrupted the Composition of the Murine Colonic Microbiota and Accelerated a Murine Model of Inflammatory Bowel Disease

    PubMed Central

    Watanabe, Yohei; Arase, Sohei; Nagaoka, Noriko; Kawai, Mitsuhisa; Matsumoto, Satoshi

    2016-01-01

    The effect of psychological stress on the gastrointestinal microbiota is widely recognized. Chronic psychological stress may be associated with increased disease activity in inflammatory bowel disease, but the relationships among psychological stress, the gastrointestinal microbiota, and the severity of colitis is not yet fully understood. Here, we examined the impact of 12-week repeated water-avoidance stress on the microbiota of two inbred strains of T cell receptor alpha chain gene knockout mouse (background, BALB/c and C57BL/6) by means of next-generation sequencing of bacterial 16S rRNA genes. In both mouse strains, knockout of the T cell receptor alpha chain gene caused a loss of gastrointestinal microbial diversity and stability. Chronic exposure to repeated water-avoidance stress markedly altered the composition of the colonic microbiota of C57BL/6 mice, but not of BALB/c mice. In C57BL/6 mice, the relative abundance of genus Clostridium, some members of which produce the toxin phospholipase C, was increased, which was weakly positively associated with colitis severity, suggesting that expansion of specific populations of indigenous pathogens may be involved in the exacerbation of colitis. However, we also found that colitis was not exacerbated in mice with a relatively diverse microbiota even if their colonic microbiota contained an expanded phospholipase C-producing Clostridium population. Exposure to chronic stress also altered the concentration of free immunoglobulin A in colonic contents, which may be related to both the loss of bacterial diversity in the colonic microbiota and the severity of the colitis exacerbation. Together, these results suggest that long-term exposure to psychological stress induces dysbiosis in the immunodeficient mouse in a strain-specific manner and also that alteration of microbial diversity, which may be related to an altered pattern of immunoglobulin secretion in the gastrointestinal tract, might play a crucial role in the

  14. Hepatocellular expression of a novel glycoprotein with sialylated difucosyl Lex activity in the active inflammatory lesions of chronic liver disease.

    PubMed Central

    Okada, Y.; Shimoe, T.; Muguruma, M.; Usumoto, R.; Tsuji, T.; Jinno, K.; Moriwaki, S.; Shin, S.; Hakomori, S.

    1988-01-01

    Hepatic expression of sialylated difucosyl Lex antigen (SDLex, NeuAc alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-) was studied with monoclonal antibody FH6, which defines this structure. Hepatocytes in the severe form of chronic active hepatitis and liver cirrhosis strongly expressed SDLex. The antigen was only weakly and focally detected in chronic persistent hepatitis. The mild form of chronic active hepatitis showed intermediate expression. SDLex expressed along the liver cell membranes displayed a honeycomb pattern when extensively expressed in the severe form of chronic active hepatitis or in liver cirrhosis. Cytoplasmic expression was faint and focal. Preferential tissue distribution was at the periphery of the hepatic lobules where the distruction of the limiting plate was present. The antigen was also expressed in sinusoidal lining cells and polymorphonuclear cells but not in the biliary epithelia. Hepatocytes expressing SDLex did not express related carbohydrate antigens, ie, Type 2 chain N-acetyllactosamine, Lex, and sialylated Lea. On subcellular fractionation, the microsome fraction contained the majority of the antigen activity. SDS-PAGE and Western blot analysis revealed one major SDLex-active glycoprotein with an apparent molecular weight of 110 kilodaltons. This glycoprotein was different from SDLex-active glycoproteins found in the sera of cancer patients. No ganglioside showed FH6 reactivity. These results indicate that liver cells in active inflammatory lesion expressed a novel glycoprotein carrying SDLex antigen in honeycomblike membrane-associated pattern. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:3341453

  15. Proven Weight Loss Methods

    MedlinePlus

    Fact Sheet Proven Weight Loss Methods What can weight loss do for you? Losing weight can improve your health in a number of ways. It can lower ... at www.hormone.org/Spanish . Proven Weight Loss Methods Fact Sheet www.hormone.org

  16. Comparison of indium-111 scintigraphy and colonoscopy with histologic study in children for evaluation of colonic chronic inflammatory bowel disease

    SciTech Connect

    Tolia, V.; Kuhns, L.R.; Chang, C.H.; Slovis, T.L. )

    1991-04-01

    Indium-111 leukocyte scanning and colonoscopy were performed in 19 children and adolescents with chronic inflammatory bowel disease to study the correlation of evaluation between these two diagnostic modalities in comparison to histologic study for colonic disease. Seven patients had ulcerative colitis, 10 had Crohn's disease, and two patients had no specific diagnosis after evaluation. The sensitivity of indium-111 scan was 18%, specificity was 62.5%, and accuracy for diagnosing colonic disease was only 37%. In comparison, sensitivity and specificity for colonoscopy were 100 and 57%, respectively. Furthermore, accuracy with colonoscopy was 84%. The authors data suggest that the usefulness of scans is limited to patients in whom standard diagnostic procedures are contraindicated. In addition, it is essential to confirm the visual diagnostic impression on colonoscopy with histologic study.

  17. [Rheumatology 2003-part I: research news concerning pathogenesis, epidemiology, diagnosis, and therapy of chronic inflammatory joint diseases].

    PubMed

    Gause, Angela; Schnabel, Armin

    2003-09-15

    Due to the partial elucidation of the immunopathogenesis of chronic inflammatory diseases during the last years, clinical rheumatology has made a rapid development, which by the consequent use of immunomodulatory therapies including recombinant proteins (biologicals) led to a significantly ameliorated prognosis of these diseases. On this basis, new research projects are continuously performed in the fields of pathogenesis, new drug development, outcome and therapy studies. New developments of imaging techniques and serologic testing facilitate a better classification and definition of disease activity and remission criteria. The current state of research in the field of rheumatoid arthritis and spondylarthropathies with its clinical consequences is reviewed in this article on the basis of the most recent data available. PMID:14551709

  18. Macrophage Polarization in AIDS: Dynamic Interface between Anti-Viral and Anti-Inflammatory Macrophages during Acute and Chronic Infection

    PubMed Central

    Burdo, Tricia H; Walker, Joshua; Williams, Kenneth C

    2015-01-01

    Monocyte and macrophage inflammation in parenchymal tissues during acute and chronic HIV and SIV infection plays a role in early anti-viral immune responses and later in restorative responses. Macrophage polarization is observed in such responses in the central nervous system (CNS) and the heart and cardiac vessels that suggest early responses are M1 type antiviral responses, and later responses favor M2 restorative responses. Macrophage polarization is unique to different tissues and is likely dictated as much by the local microenvironment as well as other inflammatory cells involved in the viral responses. Such polarization is found in HIV infected humans, and the SIV infected animal model of AIDS, and occurs even with effective anti-retroviral therapy. Therapies that directly target macrophage polarization in HIV infection have recently been implemented, as have therapies to directly block traffic and accumulation of macrophages in tissues. PMID:26500805

  19. Education to improve quality of life of people with chronic inflammatory skin conditions: a systematic review of the evidence.

    PubMed

    Pickett, K; Frampton, G; Loveman, E

    2016-06-01

    Patient and carer education has been proposed as a way of improving health-related quality of life (HRQoL) among people with chronic inflammatory skin conditions. This systematic review aimed to assess the effects of education that specifically addresses HRQoL among people with chronic inflammatory skin conditions. We searched 12 literature databases and other sources (up to July 2014). Seven randomized controlled trials (RCTs) met the review inclusion criteria. Data from these RCTs were extracted and critically appraised. Two RCTs showed that for psoriasis in adults, group-based and text message education (as adjuncts to usual care) resulted in better HRQoL and disease severity outcomes than comparators, respectively. One RCT found that group-based education for children with eczema (atopic dermatitis) and their parents resulted in greater improvements in parents' HRQoL and in the children's disease severity than no education at 12 months. The remaining RCTs evaluated an educational session for psoriasis, a website for carers of children with eczema, information on skincare and make-up use given to women with acne, and an itch-coping programme for a range of conditions, all as adjuncts to usual care. None of these RCTs found statistically significant effects on HRQoL or disease severity compared with usual care. Common features of the effective interventions were long delivery (over 6 weeks to 3 months) and delivery by a multidisciplinary team. Overall, the evidence base is currently limited and generally has an unclear risk of bias. There is a need for more large RCTs evaluating piloted and theory-based interventions. PMID:26833102

  20. Discovery of novel phenolic antioxidants as inhibitors of vascular cell adhesion molecule-1 expression for use in chronic inflammatory diseases.

    PubMed

    Meng, Charles Q; Somers, Patricia K; Hoong, Lee K; Zheng, X Sharon; Ye, Zhihong; Worsencroft, Kimberly J; Simpson, Jacob E; Hotema, Martha R; Weingarten, M David; MacDOnald, Mathew L; Hill, Russell R; Marino, Elaine M; Suen, Ki-Ling; Luchoomun, Jayraz; Kunsch, Charles; Landers, Laura K; Stefanopoulos, Dimitria; Howard, Randy B; Sundell, Cynthia L; Saxena, Uday; Wasserman, Martin A; Sikorski, James A

    2004-12-01

    Vascular cell adhesion molecule-1 (VCAM-1) mediates recruitment of leukocytes to endothelial cells and is implicated in many inflammatory conditions. Since part of the signal transduction pathway that regulates the activation of VCAM-1 expression is redox-sensitive, compounds with antioxidant properties may have inhibitory effects on VCAM-1 expression. Novel phenolic compounds have been designed and synthesized starting from probucol (1). Many of these compounds demonstrated potent inhibitory effects on cytokine-induced VCAM-1 expression and displayed potent antioxidant effects in vitro. Some of these derivatives (4o, 4p, 4w, and 4x) inhibited lipopolysaccharide (LPS)-induced secretion of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and IL-6 from human peripheral blood mononuclear cells (hPBMCs) in a concentration-dependent manner in vitro and showed antiinflammatory effects in an animal model. Compounds 4ad and 4ae are currently in clinical trials for the treatment of rheumatoid arthritis (RA) and prevention of chronic organ transplant rejection, respectively. PMID:15566311

  1. Glucocorticoid-associated osteoporosis in chronic inflammatory diseases: epidemiology, mechanisms, diagnosis, and treatment.

    PubMed

    von Scheven, Emily; Corbin, Kathleen Jo; Stagi, Stefano; Stefano, Stagi; Cimaz, Rolando

    2014-09-01

    Children with chronic illnesses such as Juvenile Idiopathic Arthritis and Crohn's disease, particularly when taking glucocorticoids, are at significant risk for bone fragility. Furthermore, when childhood illness interferes with achieving normal peak bone mass, life-long fracture risk is increased. Osteopenia and osteoporosis, which is increasingly recognized in pediatric chronic disease, likely results from numerous disease- and treatment-related factors, including glucocorticoid exposure. Diagnosing osteoporosis in childhood is complicated by the limitations of current noninvasive techniques such as DXA, which despite its limitations remains the gold standard. The risk:benefit ratio of treatment is confounded by the potential for spontaneous restitution of bone mass deficits and reshaping of previously fractured vertebral bodies. Bisphosphonates have been used to treat secondary osteoporosis in children, but limited experience and potential long-term toxicity warrant caution in routine use. This article reviews the factors that influence loss of normal bone strength and evidence for effective treatments, in particular in patients with gastrointestinal and rheumatologic disorders who are receiving chronic glucocorticoid therapy. PMID:25001898

  2. [The role of defensins in the pathogenesis of chronic-inflammatory bowel disease].

    PubMed

    Schmid, M; Fellermann, K; Wehkamp, J; Herrlinger, K; Stange, E F

    2004-04-01

    Defensins are endogenous antimicrobial peptides with a broad activity spectrum. Even at micromolar concentrations gramnegative and grampositive bacteria, but also mycobacteria, as well as fungi (candida), viruses (herpes) and protozoa (giardia lamblia) are destroyed. As part of the innate immune system defensins are expressed by the intestinal epithelium and contribute to the maintenance of the mucosal barrier. This barrier appears to be defective in inflammatory bowel diseases since on one hand, the immune response is directed against the "normal" luminal bacterial flora and on the other hand, mucosal adherent and invasive bacteria have been observed in these diseases. A defective defensin expression may well explain these phenomena. Indeed, Crohn's disease of the terminal ileum, especially if associated with a NOD2 mutation, is characterised by a diminished alpha-defensin (human defensin 5 and 6) expression, and in inflamed Crohn's colitis, in contrast to ulcerative colitis, the beta-defensin (human beta-defensins 2 and 3) response is reduced. Through a deficient chemical mucosal barrier this defect could lead to increased bacterial invasion into the intestinal mucosa and might well explain an adequate inflammatory response. Although the final proof that this deficient defensin response leads to a reduced antibacterial activity of the intestinal mucosa is still lacking, the most plausible concept of pathogenesis of Crohn's disease is a defensin deficiency syndrome. PMID:15095125

  3. Anti-nociceptive and anti-inflammatory effects of cyanocobalamin (vitamin B12) against acute and chronic pain and inflammation in mice.

    PubMed

    Hosseinzadeh, H; Moallem, S A; Moshiri, M; Sarnavazi, M S; Etemad, L

    2012-07-01

    In this study, the anti-nociceptive and anti-inflammatory effects of cyanocobalamin (Vit B12) against acute and chronic pain and inflammation were evaluated in mice. Vit B12 (0.87, 1 and 1.77 mg/kg) were injected intraperitoneally. The anti-nociceptive effects against acute pain were examined using hot-plate and writhing tests. The chronic pain was examined 14 days after sciatic nerve ligation using the hot-plate test. Morphine (10 mg/kg) was used as a positive control. Anti-inflammatory effects of Vit B12 against acute and chronic inflammation were assessed using xylene-induced edema in ears and granuloma caused by compressed cotton implantation, respectively. In these tests, sodium diclofenac (15 mg/kg) was used as a positive control. Vit B12 showed a dose related effect in acute anti-nociceptive test and increased the anti-nociceptive effect of morphine in chronic treatment. Vit B12 demonstrated an anti-nociceptive effect in chronic studies as single or continues daily treatment and increased significantly the anti-nociceptive effect of morphine. All doses of Vit B12 significantly decreased xylene-induced ear edema. Maximum anti-inflammatory effect (37.5%) was obtained at dose of 1 mg/kg. In chronic inflammation, Vit B12 significantly decreased granuloma formation in mice. In conclusion our work presents some experimental evidence supporting the administration of cyanocobalamin in controlling acute and chronic neuropathic pain. Cyanocobalamin may have anti-inflammatory effect. It may reduce tolerance to anti-nociceptive effect of morphine as well. PMID:22588629

  4. Blood Viscosity and the Expression of Inflammatory and Adhesion Markers in Homozygous Sickle Cell Disease Subjects with Chronic Leg Ulcers

    PubMed Central

    Bowers, Andre S.; Reid, Harvey L.; Greenidge, Andre; Landis, Clive; Reid, Marvin

    2013-01-01

    Objective To determine differences in TNF-α, IL-1β, IL-10, sICAM-1 concentrations, leg hypoxia and whole blood viscosity (WBV) at shear rates of 46 sec-1 and 230 sec-1 in persons with homozygous S sickle cell disease (SCD) with and without chronic leg ulceration and in AA genotype controls. Design & Methods: fifty-five age-matched participants were recruited into the study: 31 SS subjects without leg ulcers (SSn), 24 SS subjects with leg ulcers (SSu) and 18 AA controls. Haematological indices were measured using an AC.Tron Coulter Counter. Quantification of inflammatory, anti-inflammatory and adhesion molecules was performed by ELISA. Measurement of whole blood viscosity was done using a Wells Brookfield cone-plate viscometer. Quantification of microvascular tissue oxygenation was done by Visible Lightguide spectrophotometry. Results TNF-α and whole blood viscosity at 46 sec-1 and 230 sec-1 (1.75, 2.02 vs. 0.83, 1.26, p<0.05) were significantly greater in sickle cell disease subjects than in controls. There were no differences in plasma concentration of sICAM-1, IL-1β and IL-10 between SCD subjects and controls. IL-1β (median, IQR: 0.96, 1.7 vs. 0, 0.87; p<0.01) and sICAM-1 (226.5, 156.48 vs. 107.63, 121.5, p<0.005) were significantly greater in SSu group compared with SSn. However there were no differences in TNF-α (2, 3.98 vs. 0, 2.66) and IL-10 (13.34, 5.95 vs. 11.92, 2.99) concentrations between SSu and SSn. WBV in the SSu group at 46 sec-1 and at 230 Sec 1 were 1.9 (95%CI; 1.2, 3.1) and 2.3 (1.2, 4.4) times greater than in the SSn group. There were no differences in the degree of tissue hypoxia as determined by lightguide spectrophotometry. Conclusion Inflammatory, adhesion markers and WBV may be associated with leg ulceration in sickle cell disease by way of inflammation-mediated vasoocclusion/vasoconstriction. Impaired skin oxygenation does not appear to be associated with chronic ulcers in these subjects with sickle cell disease. PMID:23922670

  5. Provenance in neuroimaging.

    PubMed

    Mackenzie-Graham, Allan J; Van Horn, John D; Woods, Roger P; Crawford, Karen L; Toga, Arthur W

    2008-08-01

    Provenance, the description of the history of a set of data, has grown more important with the proliferation of research consortia-related efforts in neuroimaging. Knowledge about the origin and history of an image is crucial for establishing data and results quality; detailed information about how it was processed, including the specific software routines and operating systems that were used, is necessary for proper interpretation, high fidelity replication and re-use. We have drafted a mechanism for describing provenance in a simple and easy to use environment, alleviating the burden of documentation from the user while still providing a rich description of an image's provenance. This combination of ease of use and highly descriptive metadata should greatly facilitate the collection of provenance and subsequent sharing of data. PMID:18519166

  6. Provenance in bioinformatics workflows

    PubMed Central

    2013-01-01

    In this work, we used the PROV-DM model to manage data provenance in workflows of genome projects. This provenance model allows the storage of details of one workflow execution, e.g., raw and produced data and computational tools, their versions and parameters. Using this model, biologists can access details of one particular execution of a workflow, compare results produced by different executions, and plan new experiments more efficiently. In addition to this, a provenance simulator was created, which facilitates the inclusion of provenance data of one genome project workflow execution. Finally, we discuss one case study, which aims to identify genes involved in specific metabolic pathways of Bacillus cereus, as well as to compare this isolate with other phylogenetic related bacteria from the Bacillus group. B. cereus is an extremophilic bacteria, collected in warm water in the Midwestern Region of Brazil, its DNA samples having been sequenced with an NGS machine. PMID:24564294

  7. Implications of Chronic Daily Anti-Oxidant Administration on the Inflammatory Response to Intracortical Microelectrodes

    PubMed Central

    Potter-Baker, Kelsey A.; Stewart, Wade G.; Tomaszewski, William H.; Wong, Chun T.; Meador, William D.; Ziats, Nicholas P.; Capadona, Jeffrey R.

    2015-01-01

    Objective Oxidative stress events have been implicated to occur and facilitate multiple failure modes of intracortical microelectrodes. The goal of the present study was to evaluate the ability of a sustained concentration of an anti-oxidant and to reduce oxidative stress-mediated neurodegeneration for the application of intracortical microelectrodes. Approach Non-functional microelectrodes were implanted into the cortex of male Sprague Dawley rats for up to sixteen weeks. Half of the animals received a daily intraperitoneal injection of the natural anti-oxidant resveratrol, at 30 mg/kg. The study was designed to investigate the biodistribution of the resveratrol, and the effects on neuroinflammation/neuroprotection following device implantation. Main Results Daily maintenance of a sustained range of resveratrol throughout the implantation period resulted in fewer degenerating neurons in comparison to control animals at both two and sixteen weeks post implantation. Initial and chronic improvements in neuronal viability in resveratrol-dosed animals were correlated with significant reductions in local superoxide anion accumulation around the implanted device at two weeks after implantation. Controls, receiving only saline injections, were also found to have reduced amounts of accumulated superoxide anion locally and less neurodegeneration than controls at sixteen weeks post-implantation. Despite observed benefits, thread-like adhesions were found between the liver and diaphragm in resveratrol-dosed animals. Significance Overall, our chronic daily anti-oxidant dosing scheme resulted in improvements in neuronal viability surrounding implanted microelectrodes, which could result in improved device performance. However, due to the discovery of thread-like adhesions, further work is still required to optimize a chronic anti-oxidant dosing regime for the application of intracortical microelectrodes. PMID:26015427

  8. Quantitation in inflammatory pleural disease to distinguish tuberculous and paramalignant from chronic non-specific pleuritis.

    PubMed Central

    Capelozzi, V L; Saldiva, P H; Antonângelo, L; de Carvalho, T S; Logulo, A; de Carvalho, C R; Deheinzelin, D

    1997-01-01

    AIM: To determine by morphometry if pleural biopsies with the histopathological diagnosis of "non-specific pleuritis", malignant, and tuberculous disease could be distinguished morphologically from those with truly non-specific disease. METHODS: Each pleural biopsy was reviewed taking into account three compartments of reference: the visceral/parietal mesothelial compartment, the submesothelial screen compartment, and the submesothelial adipose tissue compartment. Normal connective tissue, granulation tissue, fibrocellular proliferation, fibrin, polymorphonuclear cells, mononuclear cells, and mesothelial cells were measured using conventional point counting procedures in terms of the fractional area occupied by each parameter within each compartment of reference. Ranking was carried out on 164 patients, based on their diagnosis: chronic non-specific disease (n = 57), tuberculosis (n = 27), malignant disease (n = 58), and conditions associated with transudative effusions (n = 22). RESULTS: Stepwise discriminant analysis of the resulting data showed that biopsies from patients with tuberculosis, malignant disease, and chronic non-specific disease could be distinguished between themselves and normal cases. Statistical differences among the four groups were observed for eight morphometric parameters related to components of inflammation and extension throughout the three pleural anatomical compartments. A robust discriminant function permitted an adequate classification of the three groups of disease in 88.41% of the cases. Pleural biopsies with fibrin incorporated within granulation tissue on the submesothelial screen compartment showed 100% specificity for patients with tuberculosis, while mononuclear cells in a band-like infiltrate on the submesothelial adipose tissue compartment showed 93.1% specificity for patients with malignant disease. The truly non-specific pleuritis was characterised by deposits of fibrin in the subpleural compartment and discrete signs of

  9. Implications of chronic daily anti-oxidant administration on the inflammatory response to intracortical microelectrodes

    NASA Astrophysics Data System (ADS)

    Potter-Baker, Kelsey A.; Stewart, Wade G.; Tomaszewski, William H.; Wong, Chun T.; Meador, William D.; Ziats, Nicholas P.; Capadona, Jeffrey R.

    2015-08-01

    Objective. Oxidative stress events have been implicated to occur and facilitate multiple failure modes of intracortical microelectrodes. The goal of the present study was to evaluate the ability of a sustained concentration of an anti-oxidant and to reduce oxidative stress-mediated neurodegeneration for the application of intracortical microelectrodes. Approach. Non-functional microelectrodes were implanted into the cortex of male Sprague Dawley rats for up to sixteen weeks. Half of the animals received a daily intraperitoneal injection of the natural anti-oxidant resveratrol, at 30 mg kg-1. The study was designed to investigate the biodistribution of the resveratrol, and the effects on neuroinflammation/neuroprotection following device implantation. Main results. Daily maintenance of a sustained range of resveratrol throughout the implantation period resulted in fewer degenerating neurons in comparison to control animals at both two and sixteen weeks post implantation. Initial and chronic improvements in neuronal viability in resveratrol-dosed animals were correlated with significant reductions in local superoxide anion accumulation around the implanted device at two weeks after implantation. Controls, receiving only saline injections, were also found to have reduced amounts of accumulated superoxide anion locally and less neurodegeneration than controls at sixteen weeks post-implantation. Despite observed benefits, thread-like adhesions were found between the liver and diaphragm in resveratrol-dosed animals. Significance. Overall, our chronic daily anti-oxidant dosing scheme resulted in improvements in neuronal viability surrounding implanted microelectrodes, which could result in improved device performance. However, due to the discovery of thread-like adhesions, further work is still required to optimize a chronic anti-oxidant dosing regime for the application of intracortical microelectrodes.

  10. [Microbiome and nutrition. The way to a future therapy for chronic inflammatory bowel diseases?].

    PubMed

    Schreiber, S; Nikolaus, S; Rosenstiel, P

    2014-08-01

    The complex microbiome of the human gut contains an excessive amount of genetic information that is more than 100-fold larger than the human genome. In patients with inflammatory bowel disease diversity of the gut microbiome is significantly reduced and moreover specific phyla are overrepresented or underrepresented. However, the functional capacity of the microflora to generate certain metabolic products containing lipids or amino acids- and more complex regulatory substances is more important that the mere annotation of the microorganisms. Modern pharmacological approaches target the functional capacity and constitution of the microbiome. An important strategy is the development of controlled release formulations that deliver defined lipid, carbohydrate or amino acid products derived from nutritional components targeting gut areas distal to the absorption zones of the upper gastrointestinal tract. PMID:25027004

  11. Genetic dysbiosis: the role of microbial insults in chronic inflammatory diseases

    PubMed Central

    Nibali, Luigi; Henderson, Brian; Sadiq, Syed Tariq; Donos, Nikos

    2014-01-01

    Thousands of bacterial phylotypes colonise the human body and the host response to this bacterial challenge greatly influences our state of health or disease. The concept of infectogenomics highlights the importance of host genetic factors in determining the composition of human microbial biofilms and the response to this microbial challenge. We hereby introduce the term ‘genetic dysbiosis’ to highlight the role of human genetic variants affecting microbial recognition and host response in creating an environment conducive to changes in the normal microbiota. Such changes can, in turn, predispose to, and influence, diseases such as: cancer, inflammatory bowel disease, rheumatoid arthritis, psoriasis, bacterial vaginosis and periodontitis. This review presents the state of the evidence on host genetic factors affecting dysbiosis and microbial misrecognition (i.e. an aberrant response to the normal microbiota) and highlights the need for further research in this area. PMID:24578801

  12. Genetic dysbiosis: the role of microbial insults in chronic inflammatory diseases.

    PubMed

    Nibali, Luigi; Henderson, Brian; Sadiq, Syed Tariq; Donos, Nikos

    2014-01-01

    Thousands of bacterial phylotypes colonise the human body and the host response to this bacterial challenge greatly influences our state of health or disease. The concept of infectogenomics highlights the importance of host genetic factors in determining the composition of human microbial biofilms and the response to this microbial challenge. We hereby introduce the term 'genetic dysbiosis' to highlight the role of human genetic variants affecting microbial recognition and host response in creating an environment conducive to changes in the normal microbiota. Such changes can, in turn, predispose to, and influence, diseases such as: cancer, inflammatory bowel disease, rheumatoid arthritis, psoriasis, bacterial vaginosis and periodontitis. This review presents the state of the evidence on host genetic factors affecting dysbiosis and microbial misrecognition (i.e. an aberrant response to the normal microbiota) and highlights the need for further research in this area. PMID:24578801

  13. Serum Vitamin A and Inflammatory Markers in Individuals with and without Chronic Obstructive Pulmonary Disease

    PubMed Central

    Caram, L. M. O.; Amaral, R. A. F.; Ferrari, R.; Tanni, S. E.; Correa, C. R.; Paiva, S. A. R.; Godoy, I.

    2015-01-01

    Background. Vitamin A is essential for the preservation and integrity of the lung epithelium and exerts anti-inflammatory effects. Objective. Evaluating vitamin A in the serum and sputum and testing its correlation with inflammatory markers in individuals with or without COPD. Methods. We evaluated dietary intake, serum and sputum vitamin A, tumor necrosis factor alpha, interleukin- (IL-) 6, IL-8, and C-reactive protein in 50 COPD patients (age = 64.0 ± 8.8 y; FEV1 (forced expiratory volume in the first second) (%) = 49.8 ± 16.8) and 50 controls (age = 48.5 ± 7.4 y; FEV1 (%) = 110.0 ± 15.7). Results. COPD exhibited lower serum vitamin A (1.8 (1.2–2.1) versus 2.1 (1.8–2.4) μmol/L, P < 0.001) and lower vitamin A intake (636.9 (339.6–1349.6) versus 918.0 (592.1–1654.6) RAE, P = 0.05) when compared with controls. Sputum concentration of vitamin A was not different between groups. Sputum vitamin A and neutrophils were negatively correlated (R2 = −0.26; P = 0.03). Smoking (0.197, P = 0.042) exhibited positive association with serum vitamin A. COPD was associated with lower serum concentrations of vitamin A without relationship with the systemic inflammation. Conclusions. Serum concentration of vitamin A is negatively associated with the presence of COPD and positively associated with smoking status. Sputum retinol is quantifiable and is negatively influenced by neutrophils. Although COPD patients exhibited increased inflammation it was not associated with serum retinol. PMID:26339144

  14. The role of inflammatory cytokines and ERK1/2 signaling in chronic prostatitis/chronic pelvic pain syndrome with related mental health disorders

    PubMed Central

    Hu, Chao; Yang, Hualan; Zhao, Yanfang; Chen, Xiang; Dong, Yinying; Li, Long; Dong, Yehao; Cui, Jiefeng; Zhu, Tongyu; Zheng, Ping; Lin, Ching-Shwun; Dai, Jican

    2016-01-01

    Mental health disorders(MHD) in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) have been widely studied. However, the underlying role of inflammatory cytokines and their associated signaling pathways have not been investigated. Here, we report the potential role of cytokines and associated signaling pathways in CP/CPPS patients with MHD and in a CP/CPPS animal model. CP/CPPS patients (n = 810) and control subjects (n = 992) were enrolled in this case-control multicenter study, and serum cytokine levels were measured. Male Sprague-Dawley rats received multiple intracutaneous injections of an immuno-agent along with a pertussis-diphtheria-tetanus triple vaccine for autoimmune CP/CPPS development. The results revealed that, in CP/CPPS patients with significant MHD, elevated IL-1α, IL-1β, IL-4, IL-13, and TNF-α serum levels were observed. The above five cytokines in CP/CPPS rats were significantly elevated in prostate tissue (p < 0.05), and IL-1β levels were elevated in serum and cerebrospinal fluid. In behavioral tests, CP/CPPS rats showed anxiety- and depression-like symptoms, and impaired spatial and associative memory performance (p < 0.05). In the CP/CPPS group, ERK1/2 phosphorylation levels were increased in the amygdala and nucleus accumbens, and decreased in the hippocampus, but not caudate nucleus. Thus, prostate-derived cytokines, especially IL-1β, cross the blood brain barrier and may lead to enhanced ERK1/2 signaling in several brain areas, possibly underlying induction of CP/CPPS-related MHD. PMID:27334333

  15. The role of inflammatory cytokines and ERK1/2 signaling in chronic prostatitis/chronic pelvic pain syndrome with related mental health disorders.

    PubMed

    Hu, Chao; Yang, Hualan; Zhao, Yanfang; Chen, Xiang; Dong, Yinying; Li, Long; Dong, Yehao; Cui, Jiefeng; Zhu, Tongyu; Zheng, Ping; Lin, Ching-Shwun; Dai, Jican

    2016-01-01

    Mental health disorders(MHD) in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) have been widely studied. However, the underlying role of inflammatory cytokines and their associated signaling pathways have not been investigated. Here, we report the potential role of cytokines and associated signaling pathways in CP/CPPS patients with MHD and in a CP/CPPS animal model. CP/CPPS patients (n = 810) and control subjects (n = 992) were enrolled in this case-control multicenter study, and serum cytokine levels were measured. Male Sprague-Dawley rats received multiple intracutaneous injections of an immuno-agent along with a pertussis-diphtheria-tetanus triple vaccine for autoimmune CP/CPPS development. The results revealed that, in CP/CPPS patients with significant MHD, elevated IL-1α, IL-1β, IL-4, IL-13, and TNF-α serum levels were observed. The above five cytokines in CP/CPPS rats were significantly elevated in prostate tissue (p < 0.05), and IL-1β levels were elevated in serum and cerebrospinal fluid. In behavioral tests, CP/CPPS rats showed anxiety- and depression-like symptoms, and impaired spatial and associative memory performance (p < 0.05). In the CP/CPPS group, ERK1/2 phosphorylation levels were increased in the amygdala and nucleus accumbens, and decreased in the hippocampus, but not caudate nucleus. Thus, prostate-derived cytokines, especially IL-1β, cross the blood brain barrier and may lead to enhanced ERK1/2 signaling in several brain areas, possibly underlying induction of CP/CPPS-related MHD. PMID:27334333

  16. Chronic granulomatous disease: a review of the infectious and inflammatory complications

    PubMed Central

    2011-01-01

    Chronic Granulomatous Disease is the most commonly encountered immunodeficiency involving the phagocyte, and is characterized by repeated infections with bacterial and fungal pathogens, as well as the formation of granulomas in tissue. The disease is the result of a disorder of the NADPH oxidase system, culminating in an inability of the phagocyte to generate superoxide, leading to the defective killing of pathogenic organisms. This can lead to infections with Staphylococcus aureus, Psedomonas species, Nocardia species, and fungi (such as Aspergillus species and Candida albicans). Involvement of vital or large organs can contribute to morbidity and/or mortality in the affected patients. Major advances have occurred in the diagnosis and treatment of this disease, with the potential for gene therapy or stem cell transplantation looming on the horizon. PMID:21624140

  17. Induction of proinflammatory cytokines by a soluble factor of Propionibacterium acnes: implications for chronic inflammatory acne.

    PubMed

    Vowels, B R; Yang, S; Leyden, J J

    1995-08-01

    Although many cytokines have been implicated in the development and persistence of inflammatory immune responses, it is unknown if any of these are important in inflammatory acne. This study investigated the production of the proinflammatory cytokines interleukin-8 (IL-8), IL-1 beta, and tumor necrosis factor alpha (TNF-alpha) by human monocytic cell lines, ThP-1 and U937, and by freshly isolated peripheral blood mononuclear cells from acne patients. Both Propionibacterium acnes and supernatants obtained from 72-h P. acnes cultures could induce significant concentrations of IL-1 beta, TNF-alpha, and IL-8 by both cell lines and by peripheral blood mononuclear cells as determined by enzyme-linked immunosorbent assay. There was no significant difference between acne and non-acne subjects. Endotoxin quantification and addition of polymyxin B to assays indicated no lipopolysaccharide (LPS) contamination. P. acnes supernatant was fractionated into components with molecular weights of < 3,000, < 10,000, and < 30,000 and assayed for the ability to induce IL-8 and TNF production in ThP-1 cells. Nearly 90% of the original activity was found in the < 30,000-molecular-weight fraction, 50% was in the < 10,000-molecular-weight fraction, and only 15% remained in the < 3,000-molecular-weight fraction. The effluent from the < 3,000-molecular-weight fraction contained about 70% activity, indicating that the inducing factor was not retained in the membrane. Incubation of P. acnes supernatant with various concentrations of mutanolysin or lysozyme resulted in a loss of 60% of the original activity. The addition of jimson lectin, which binds peptidoglycan, resulted in a loss of 70% of the activity in a dose-response manner, whereas peanut lectin had little or no effect on the activity. Heating of the P. acnes supernatant to 65 degrees C also had no effect on the activity. Blocking of CD14, a receptor for both LPS and peptidoglycan, reduced cytokine production by > 50%, suggesting that

  18. Gut microbiome diversity in acute infective and chronic inflammatory gastrointestinal diseases in North India.

    PubMed

    Kedia, Saurabh; Rampal, Ritika; Paul, Jaishree; Ahuja, Vineet

    2016-07-01

    The disease profile in the Indian population provides a unique opportunity for studying the host microbiome interaction in both infectious (amebiasis) and autoimmune diseases like inflammatory bowel disease (IBD) from a similar environment and genetic background. Analysis of fecal samples from untreated amebic liver abscess (ALA) patients, Entamoeba histolytica (Eh)-negative and -positive asymptomatic individuals, and pus samples from naive ALA patients revealed a significant reduction in Lactobacillus in asymptomatic individuals (Eh +ve) and ALA patients. Two anaerobic genera, namely Bacteroides and Peptostreptococcus, were detected in naive ALA pus samples. Analysis of fecal samples from amoebic colitis patients showed a significant decline in population of Bacteroides, Clostridium coccoides and leptum subgroup, Lactobacillus, Campylobacter, and Eubacterium, whereas a significant increase in Bifidobacterium was observed. Mucosa-associated bacterial flora analysis from IBD patients and healthy controls revealed a significant difference in concentration of bacteria among predominating and subdominating genera between ulcerative colitis (UC), Crohn's disease (CD) patients, and controls. In contrast to the mucosal studies, we found a significant increase in lactobacilli population in fecal samples of active UC patients. Another study revealed a significant decrease of Clostridium coccoides and leptum clusters in fecal samples of active UC patients along with decreased concentrations of fecal SCFAs, especially of n-butyrate, iso-butyrate, and acetate. We therefore found similar perturbations in gut microbiome in both infectious and autoimmune diseases, indicating inflammation to be the major driver for changes in gut microbiome. PMID:26994772

  19. Escherichia coli in chronic inflammatory bowel diseases: An update on adherent invasive Escherichia coli pathogenicity

    PubMed Central

    Martinez-Medina, Margarita; Garcia-Gil, Librado Jesus

    2014-01-01

    Escherichia coli (E. coli), and particularly the adherent invasive E. coli (AIEC) pathotype, has been increasingly implicated in the ethiopathogenesis of Crohn’s disease (CD). E. coli strains with similar pathogenic features to AIEC have been associated with other intestinal disorders such as ulcerative colitis, colorectal cancer, and coeliac disease, but AIEC prevalence in these diseases remains largely unexplored. Since AIEC was described one decade ago, substantial progress has been made in deciphering its mechanisms of pathogenicity. However, the molecular bases that characterize the phenotypic properties of this pathotype are still not well resolved. A review of studies focused on E. coli populations in inflammatory bowel disease (IBD) is presented here and we discuss about the putative role of this species on each IBD subtype. Given the relevance of AIEC in CD pathogenesis, we present the latest research findings concerning AIEC host-microbe interactions and pathogenicity. We also review the existing data regarding the prevalence and abundance of AIEC in CD and its association with other intestinal diseases from humans and animals, in order to discuss the AIEC disease- and host-specificity. Finally, we highlight the fact that dietary components frequently found in industrialized countries may enhance AIEC colonization in the gut, which merits further investigation and the implementation of preventative measures. PMID:25133024

  20. Magnetic resonance imaging in children and adolescents with chronic inflammatory bowel disease

    PubMed Central

    Mentzel, Hans-Joachim; Reinsch, Steffen; Kurzai, Monika; Stenzel, Martin

    2014-01-01

    Inflammatory bowel diseases (IBD) represent challenges, both from a diagnostic, and therapeutic point of view. Deep-seated anatomic structures are difficult to assess by ultrasound technique alone. As radiation-free alternative cross-sectional imaging method, magnetic resonance imaging of the intestinal structures is costly and time-consuming. Examination of pediatric patients imply additional considerations: reduction of body motions in younger children and consideration of the most appropriate preparation, and examination technique. The demanding Sellink technique is the only means for appropriately distending the lesser intestine in order to detect small bowel strictures. Oral intake of contrast medium (CM) alone shows its limitations regarding distensibility. The need for intravenous contrast media application needs to be considered, too. Active inflammation of both intestinal wall, and mesentery can be demonstrated accurately. Nevertheless, viable alternatives to CM application is desirable, considering non-negligible adverse reactions. Recent data suggest diffusion weighted imaging might fill this diagnostic gap. Irrespective of sequence technique chosen, bowel movement remains a major obstacle. Antispasmolytics in their function as smooth muscle relaxants help in improving image quality, however, their use in children might be off-label. Optimal preparation for the examination and appropriate imaging technique allow for diagnosing typical patterns of changes in IBD, such as bowel wall thickening, ulcers, mural stratification, strictures, creeping fat, and comb sign, and lymphadenopathy. The article gives a detailed overview of current significance of magnetic resonance imaging pediatric patients suffering from IBD, considering indications, limitations, and safety aspects. PMID:24574794

  1. [The peroxisome-proliferator-activated gamma receptor and chronic inflammatory bowel disease (PPARgamma and IBD)].

    PubMed

    Rousseaux, Christel; Desreumaux, Pierre

    2006-01-01

    PPARgamma has been recently described as being a gene of susceptibility for Intestinal Bowel Diseases (IBD) as NOD2/CARD15 gene. IBD are pathologies due to an abnormal immune response, in genetically predisposed patients, to the bacteria of the intestinal flora. PPARgamma, known for its significant role in adipogenesis, is strongly expressed by the epithelial cells of the colon mucosa. PPARgamma is implicated in the regulation of inflammation. Indeed, agonists of this nuclear receptor decrease strongly the intensity of inflammation during experimental colitis induced by chemical agents. A deficit of PPARgamma in patients with ulcerative colitis has been highlighted, that could in part explain the acute inflammation. In addition, bacteria, including those of the commensal flora, are able to regulate PPARgamma. Toll Like Receptor-4 (TLR-4), responsible for the recognition of bacterial motif as lipopolysaccharide (LPS), is implicated in PPARgamma regulation and its anti-inflammatory properties. All these arguments make of PPARgamma a very interesting therapeutic target for the treatment of IBD. PMID:17151549

  2. Daily cytokine fluctuations, driven by leptin, are associated with fatigue severity in chronic fatigue syndrome: evidence of inflammatory pathology

    PubMed Central

    2013-01-01

    Background Chronic fatigue syndrome (CFS) is a debilitating disorder characterized by persistent fatigue that is not alleviated by rest. The lack of a clearly identified underlying mechanism has hindered the development of effective treatments. Studies have demonstrated elevated levels of inflammatory factors in patients with CFS, but findings are contradictory across studies and no biomarkers have been consistently supported. Single time-point approaches potentially overlook important features of CFS, such as fluctuations in fatigue severity. We have observed that individuals with CFS demonstrate significant day-to-day variability in their fatigue severity. Methods Therefore, to complement previous studies, we implemented a novel longitudinal study design to investigate the role of cytokines in CFS pathophysiology. Ten women meeting the Fukuda diagnostic criteria for CFS and ten healthy age- and body mass index (BMI)-matched women underwent 25 consecutive days of blood draws and self-reporting of symptom severity. A 51-plex cytokine panel via Luminex was performed for each of the 500 serum samples collected. Our primary hypothesis was that daily fatigue severity would be significantly correlated with the inflammatory adipokine leptin, in the women with CFS and not in the healthy control women. As a post-hoc analysis, a machine learning algorithm using all 51 cytokines was implemented to determine whether immune factors could distinguish high from low fatigue days. Results Self-reported fatigue severity was significantly correlated with leptin levels in six of the participants with CFS and one healthy control, supporting our primary hypothesis. The machine learning algorithm distinguished high from low fatigue days in the CFS group with 78.3% accuracy. Conclusions Our results support the role of cytokines in the pathophysiology of CFS. PMID:23570606

  3. Fluoroquinolone–macrolide combination therapy for chronic bacterial prostatitis: retrospective analysis of pathogen eradication rates, inflammatory findings and sexual dysfunction

    PubMed Central

    Magri, Vittorio; Montanari, Emanuele; Škerk, Višnja; Markotić, Alemka; Marras, Emanuela; Restelli, Antonella; Naber, Kurt G; Perletti, Gianpaolo

    2011-01-01

    We previously demonstrated the safety and efficacy of fluoroquinolone–macrolide combination therapy in category II chronic bacterial prostatitis (CBP). The aim of this study is to retrospectively compare the microbiological and clinical findings of two treatment schemes for CBP based on the combination of azithromycin (500 mg, thrice-weekly) with a once-daily 500- or 750-mg dose of ciprofloxacin (Cipro-500 or Cipro-750 cohort, respectively). Combined administration of azithromycin (1500 mg week−1) with ciprofloxacin at the rate of 750 mg day−1 for 4 weeks rather than at 500 mg day−1 for 6 weeks increased the eradication rates from 62.35% to 77.32% and the total bacteriological success from 71.76% to 85.57%. A significant decrease in pain and voiding signs/symptoms and a significant reduction in inflammatory leukocyte counts and serum prostate-specific antigen (PSA) were sustained throughout an 18-month follow-up period in both groups. Ejaculatory pain, haemospermia and premature ejaculation were significantly attenuated on microbiological eradication in both groups, but the latter subsided more promptly in the Cipro-750 cohort. In total, 59 Cipro-750 patients showed mild-to-severe erectile dysfunction (ED) at baseline, while 22 patients had no ED on microbiological eradication and throughout the follow-up period. In conclusion fluoroquinolone–macrolide therapy resulted in pathogen eradication and CBP symptom attenuation, including pain, voiding disturbances and sexual dysfunction. A once-daily 750-mg dose of ciprofloxacin for 4 weeks showed enhanced eradication rates and lower inflammatory white blood cell counts compared to the 500-mg dose for 6 weeks. Our results are open to further prospective validation. PMID:21765442

  4. Low-Dose Tramadol and Non-Steroidal Anti-Inflammatory Drug Combination Therapy Prevents the Transition to Chronic Low Back Pain

    PubMed Central

    Orita, Sumihisa; Yamauchi, Kazuyo; Suzuki, Takane; Suzuki, Miyako; Sakuma, Yoshihiro; Kubota, Go; Oikawa, Yasuhiro; Sainoh, Takeshi; Sato, Jun; Fujimoto, Kazuki; Shiga, Yasuhiro; Abe, Koki; Kanamoto, Hirohito; Inoue, Masahiro; Kinoshita, Hideyuki; Takahashi, Kazuhisa; Ohtori, Seiji

    2016-01-01

    Study Design Retrospective study. Purpose To determine whether low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy could prevent the transition of acute low back pain to chronic low back pain. Overview of Literature Inadequately treated early low back pain transitions to chronic low back pain occur in approximately 30% of affected individuals. The administration of non-steroidal anti-inflammatory drugs is effective for treatment of low back pain in the early stages. However, the treatment of low back pain that is resistant to non-steroidal anti-inflammatory drugs is challenging. Methods Patients who presented with acute low back pain at our hospital were considered for inclusion in this study. After the diagnosis of acute low back pain, non-steroidal anti-inflammatory drug administration was started. Forty patients with a visual analog scale score of >5 for low back pain 1 month after treatment were finally enrolled. The first 20 patients were included in a non-steroidal anti-inflammatory drug group, and they continued non-steroidal anti-inflammatory drug therapy for 1 month. The next 20 patients were included in a combination group, and they received low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy for 1 month. The incidence of adverse events and the improvement in the visual analog scale score at 2 months after the start of treatment were analyzed. Results No adverse events were observed in the non-steroidal anti-inflammatory drug group. In the combination group, administration was discontinued in 2 patients (10%) due to adverse events immediately following the start of tramadol administration. At 2 months, the improvement in the visual analog scale score was greater in the combination group than in the non-steroidal anti-inflammatory drug group (p<0.001). Conclusions Low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy might decrease the incidence of adverse events and prevent

  5. Inflammatory and Immune Response Genes Polymorphisms are Associated with Susceptibility to Chronic Obstructive Pulmonary Disease in Tatars Population from Russia.

    PubMed

    Korytina, Gulnaz Faritovna; Akhmadishina, L Z; Kochetova, O V; Aznabaeva, Y G; Zagidullin, Sh Z; Victorova, T V

    2016-08-01

    Chronic obstructive pulmonary disease (COPD) is a complex chronic inflammatory disease of the respiratory system affecting primarily distal respiratory pathways and lung parenchyma. This work was designed as a case-control study aimed at investigating the association of COPD with polymorphisms in inflammatory and immune response genes (JAK1, JAK3, STAT1, STAT3, NFKB1, IL17A, ADIPOQ, ADIPOR1, etc.) in Tatar population from Russia. Ten SNPs (rs310216, rs3212780, rs12693591, rs2293152, rs28362491, rs4711998, rs1974226, rs1501299, rs266729, and rs12733285) were genotyped by the real-time polymerase chain reaction (TaqMan assays) in a case-control study (425 COPD patients and 457 in the control group, from Ufa, Russia). Logistic regression was used to detect the association of SNPs in different models. Linear regression analyses were performed to estimate the relationship between SNPs and lung function parameters and pack-years. In Tatar population, significant associations of JAK1 (rs310216) (P = 0.0002, OR 1.70 in additive model), JAK3 (rs3212780) (P = 0.001, OR 1.61 in dominant model), and IL17A (rs1974226) (P = 0.0037, OR 2.31 in recessive model) with COPD were revealed. The disease risk was higher in carriers of insertion allele of NFKB1 (rs28362491) (P = 0.045, OR 1.22). We found a significant gene-by-environment interaction of smoking status and IL17A (rs1974226) (P interact = 0.016), JAK3 (rs3212780) (P interact = 0.031), ADIPOQ (rs266729) (P interact = 0.013), and ADIPOR1 (rs12733285) (P interact = 0.018). The relationship between the rs4711998, rs1974226, rs310216, rs3212780, rs28362491, and smoking pack-years was found (P = 0.045, P = 0.004, P = 0.0005, P = 0.021, and P = 0.042). A significant genotype-dependent variation of forced vital capacity was observed for NFKB1 (rs28362491) (P = 0.017), ADIPOR1 (rs12733285) (P = 0.043), and STAT1 (rs12693591) (P = 0.048). The genotypes of STAT1 (rs12693591) (P = 0.013) and JAK1 (rs

  6. Acute and long-term effect of infliximab on humoral and echocardiographic parameters in patients with chronic inflammatory diseases.

    PubMed

    Tomáš, L'ubomír; Lazúrová, Ivica; Pundová, Lýdia; Oetterová, Mária; Zakuciová, Mária; Petrášová, Darina; Studenčan, Martin

    2013-01-01

    Tumor necrosis factor alpha (TNF-alpha) plays an important role in the pathogenesis of chronic inflammatory diseases, i.e., rheumatoid arthritis (RA), ankylosing spondylitis (AS), Crohn's disease (CD), and ulcerative colitis (UC). Anti-TNF-alpha strategies are successfully used in their treatment. However, their effect on heart function is still uncertain. The objectives of the study were to examine the acute and long-term effect of infliximab on the heart morphology and function in patients with chronic inflammatory disorders. Thirty-one patients (21 men and 10 women) were included. Ten percent of them were diagnosed with RA, 22.5 % with AS, 22.5 % with CD, and 45 % with UC, respectively. N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) was measured before and immediately after infliximab administration at the beginning of the study and in the sixth and 12th months. Echocardiography was performed at baseline and in the sixth and 12th months. There was a significant increase in NT-proBNP after the first infliximab infusion (88.40 ± 14.09 vs. 95.24 ± 14.28 pg/ml, p = 0.0046) and similar response was detected after each infusion in the sixth and 12th months. Plasma NT-proBNP slightly but not significantly decreased (88.40 ± 14.09 vs. 81.74 ± 23.14 pg/ml, p = 0.583, and 88.40 ± 14.09 vs. 56.83 ± 17.77 pg/ml, p = 0.0576, in the sixth and 12th months, respectively). There were no significant changes in echocardiographic structural and functional parameters of the left ventricle during follow-up. Plasma NT-proBNP mildly but significantly increases immediately after infliximab infusion. However, long-term infliximab administration does not deteriorate both cardiac morphology and function. PMID:23010850

  7. Prevalence of Chronic Axial Pain, Inflammatory Back Pain, and Spondyloarthritis in Diagnosed Psoriasis

    PubMed Central

    Thom, Nicole; Ritchlin, Christopher T.; Zhang, Xiao; Reveille, John; Weisman, Michael H.

    2015-01-01

    Objective To provide prevalence estimates for inflammatory back pain (IBP) and spondyloarthritis (SpA) in those subjects with psoriasis using 2009–2010 National Health and Nutrition Examination Survey (NHANES) data. Methods In the NHANES 2009–2010 sample set, 6,684 persons ages 20–69 years were screened for participation, and 5,103 answered questions regarding onset of back pain, location of pain, and functional limitations. Data set assembly and statistical analysis were performed using SASTM and SUDAAN software. SEs were estimated by Taylor series linearization. The equality of the prevalence estimates for selected variables was tested (univariately) at an alpha level of 0.05 using 2-sided Student’s t-test with appropriate degrees of freedom. Results A total of 148 persons had self-reported medically diagnosed psoriasis. The psoriasis group versus the nonpsoriasis group had a significantly higher prevalence of axial pain using the 3-month duration criterion (31.1% versus 18.9%; P = 0.04) and alternating buttock pain (7.2% versus 2.4%; P = 0.03) and more frequently met IBP criteria from Berlin criteria 7b and 8a (P = 0.04 and 0.02, respectively). The prevalence of SpA was significantly higher in the psoriasis group versus the nonpsoriasis group when using Amor or European Spondyloarthritis Study Group criteria (14.3% versus 1.5%; P < 0.001). Sudden onset of axial pain was significantly higher in the psoriasis group (23.3% versus 13.0%; P = 0.01). Conclusion There is a higher prevalence of lower axial pain, IBP, SpA, and alternating buttock pain associated with a prior diagnosis of psoriasis. These data may influence the way psoriasis patients are approached in primary care and specialty clinics. PMID:25469666

  8. Association of dialysis adequacy with nutritional and inflammatory status in patients with chronic kidney failure.

    PubMed

    Hemayati, Roya; Lesanpezeshki, Mahboub; Seifi, Sepideh

    2015-11-01

    The number of patients with dialysis-dependent renal failure has increased in the past years worldwide. Several parameters have been introduced for the quantitative assessment of dialysis adequacy. The National Cooperative Dialysis Study results indicated that Kt/V and time-averaged concentration of urea (TAC) are predictors of mortality in patients who receive maintenance hemodialysis (HD). Also, the protein catabolic ratio (PCR), which is an indicator of nutritional status, can predict patients' mortality. Our aim was to assess the impact of parameters that show dialysis adequacy on indices of nutrition or inflammation. A total of 46 patients were included in the study; eight patients were excluded during the course of the study and 38 patients were enrolled in the final analysis. All patients were receiving HD for at least for three months. HD was administered three times per week and the study lasted for two months. Kt/V, TAC and PCR were assessed at the beginning of the study based on patients' urea and blood urea nitrogen in the first week of our study; these calculations were repeated at the end of the first and second months using the mean of the mentioned values in the month. Both adequacy indices significantly and positively correlated with changes in PCR (P <0.001). However, no significant correlation was detectable between Kt/V and TAC with either body mass index and albumin or C-reactive protein. Based on the Kt/V values, patients with adequate dialysis had slower decrease in the PCR (P <0.001). Our results indicate that adequacy of dialysis is correlated with patients' nutritional status. No correlation was observed between dialysis adequacy and inflammatory status. PMID:26586053

  9. Acute and chronic saturated fatty acid treatment as a key instigator of the TLR-mediated inflammatory response in human adipose tissue, in vitro☆

    PubMed Central

    Youssef-Elabd, Elham M.; McGee, Kirsty C.; Tripathi, Gyanendra; Aldaghri, Nasser; Abdalla, Mohga S.; Sharada, Hayat M.; Ashour, Esmat; Amin, Ashraf I.; Ceriello, Antonio; O'Hare, Joseph P.; Kumar, Sudhesh; McTernan, Philip G.; Harte, Alison L.

    2012-01-01

    A post-prandial increase in saturated fatty acids (SFAs) and glucose (Glc) activates an inflammatory response, which may be prolonged following restoration of physiological SFAs and Glc levels — a finding referred to as ‘metabolic memory'. This study examined chronic and oscillating SFAs and Glc on the inflammatory signalling pathway in human adipose tissue (AT) and adipocytes (Ads) and determined whether Ads are subject to “metabolic memory.” Abdominal (Abd) subcutaneous (Sc) explants and Ads were treated with chronic low glucose (L-Glc): 5.6 mM and high glucose (H-Glc): 17.5 mM, with low (0.2 mM) and high (2 mM) SFA for 48 h. Abd Sc explants and Ads were also exposed to the aforementioned treatment regimen for 12-h periods, with alternating rest periods of 12 h in L-Glc. Chronic treatment with L-Glc and high SFAs, H-Glc and high SFAs up-regulated key factors of the nuclear factor-κB (NFκB) pathway in Abd Sc AT and Ads (TLR4, NFκB; P<.05), whilst down-regulating MyD88. Oscillating Glc and SFA concentrations increased TLR4, NFκB, IKKβ (P<.05) in explants and Ads and up-regulated MyD88 expression (P<.05). Both tumor necrosis factor α and interleukin 6 (P<.05) secretion were markedly increased in chronically treated Abd Sc explants and Ads whilst, with oscillating treatments, a sustained inflammatory effect was noted in absence of treatment. Therefore, SFAs may act as key instigators of the inflammatory response in human AT via NFκB activation, which suggests that short-term exposure of cells to uncontrolled levels of SFAs and Glc leads to a longer-term inflammatory insult within the Ad, which may have important implications for patients with obesity and Type 2 diabetes. PMID:21414768

  10. Targeting the NLRP3 inflammasome in chronic inflammatory diseases: current perspectives

    PubMed Central

    Ozaki, Ema; Campbell, Matthew; Doyle, Sarah L

    2015-01-01

    The inflammasome is a molecular platform formed by activation of an innate immune pattern recognition receptor seed, such as NLRP3. Once activated, NLRP3 recruits the adapter ASC (apoptosis-related speck-like protein containing a caspase recruitment domain), which in turn recruits procaspase-1. Procaspase-1 autocatalyzes its cleavage and activation, resulting in maturation of the precursor forms of interleukin (IL)-1β and IL-18 into active proinflammatory cytokines and initiation of pyroptotic cell death. The NLRP3 inflammasome has been implicated in the pathogenesis of a wide variety of diseases, including genetically inherited autoinflammatory conditions as well as chronic diseases in which NLRP3 is abnormally activated. The NLRP3 inflammasome has been linked to diseases such as Alzheimer’s disease, atherosclerosis, metabolic syndrome, and age-related macular degeneration. In this review, we describe the NLRP3 inflammasome complex and its activation in disease, and detail the current therapies that modulate either the NLRP3 inflammasome complex itself or the two cytokines it is responsible for activating, ie, IL-1β and IL-18. PMID:25653548

  11. Chronic inflammatory pain upregulates expression of P2Y2 receptor in small-diameter sensory neurons.

    PubMed

    Zhu, Huiqin; Yu, Yi; Zheng, Lingyan; Wang, Lu; Li, Chenli; Yu, Jiangyuan; Wei, Jing; Wang, Chuang; Zhang, Junfang; Xu, Shujun; Wei, Xiaofei; Cui, Wei; Wang, Qinwen; Chen, Xiaowei

    2015-12-01

    Roles of ionotropic purinergic (P2X) receptors in chronic pain have been intensively investigated. However, the contribution of metabotropic purinergic (P2Y) receptors to pathological pain is controversial. In the present study, using single cell RT-PCR (reverse transcription-polymerase chain reaction) and single cell nested-PCR techniques, we examined the expression of P2X(2), P2X(3), P2Y(1) and P2Y(2) mRNA transcripts in retrogradely labeled cutaneous sensory neurons from mouse lumber dorsal root ganglia (DRGs) following peripheral inflammation. The percentage of cutaneous sensory neurons expressing P2Y(2) mRNA transcripts increased after complete Freund's adjuvant (CFA) treatment. Particularly, the P2Y(2) mRNA transcripts were more frequently detected in small-diameter cutaneous neurons from CFA-treated mice than those from control mice. Coexpression of P2Y(2) and P2X (P2X(2) or P2X(3)) mRNAs was more frequently observed in cutaneous sensory neurons from CFA-treated mice relative to controls. Pain behavioral tests showed that the blockade of P2Y receptors by suramin attenuated mechanical allodynia evoked either by CFA or uridine triphosphate (UTP), an endogenous P2Y(2) and P2Y(4) agonist. These results suggest that chronic inflammatory pain enhances expression of P2Y(2) receptor in peripheral sensory neurons that innervate the injured tissue and the activation of P2Y receptors contributes to mechanical allodynia following inflammation. PMID:26062804

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

    PubMed Central

    Uzkeser, Hulya; Cadirci, Elif; Halici, Zekai; Odabasoglu, Fehmi; Polat, Beyzagul; Yuksel, Tugba Nurcan; Ozaltin, Seda; Atalay, Fadime

    2012-01-01

    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. PMID:22665951

  13. Smoking-induced expression of the GPR15 gene indicates its potential role in chronic inflammatory pathologies.

    PubMed

    Kõks, Gea; Uudelepp, Mari-Liis; Limbach, Maia; Peterson, Pärt; Reimann, Ene; Kõks, Sulev

    2015-11-01

    Despite the described clear epigenetic effects of smoking, the effect of smoking on genome-wide gene expression in the blood is obscure. We therefore studied the smoking-induced changes in the gene-expression profile of the peripheral blood. RNA was extracted from the whole blood of 48 individuals with a detailed smoking history (24 never-smokers, 16 smokers, and 8 ex-smokers). Gene-expression profiles were evaluated with RNA sequencing, and results were analyzed separately in 24 men and 24 women. In the male smokers, 13 genes were statistically significantly (false-discovery rate <0.1) differentially expressed; in female smokers, 5 genes. Although most of the differentially expressed genes were different between the male and female smokers, the G-protein-coupled receptor 15 gene (GPR15) was differentially expressed in both male and female smokers compared with never-smokers. Analysis of GPR15 methylation identified significantly greater hypomethylation in smokers compared with that in never-smokers. GPR15 is the chemoattractant receptor that regulates T-cell migration and immunity. Up-regulation of GPR15 could explain to some extent the health hazards of smoking with regard to chronic inflammatory diseases. PMID:26348578

  14. Autoantibodies to type II collagen: occurrence in rheumatoid arthritis, other arthritides, autoimmune connective tissue diseases, and chronic inflammatory syndromes.

    PubMed Central

    Choi, E K; Gatenby, P A; McGill, N W; Bateman, J F; Cole, W G; York, J R

    1988-01-01

    Serum IgG antibodies to native and denatured human type II collagen (Col II) were measured using an enzyme linked immunosorbent assay (ELISA). One hundred and thirty one patients with various forms of arthritis such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PSA). Reiter's Syndrome (RS), osteoarthritis (OA), and gout, 60 with autoimmune connective tissue disease, and 37 with the chronic inflammatory conditions--graft versus host disease and leprosy--were studied. With the exception of RS, PSA, OA, and gout, significant levels of Col II antibodies were detected in each disease group. Blocking studies with types I and II collagen on selected serum samples confirmed the specificity to native Col II, though some cross reactivity was apparent with denatured collagen. The patients with RA who were Col II antibody positive tended to fall into stage III of disease progression. There was, however, no correlation with rheumatoid factor, erythrocyte sedimentation rate, or disease duration and this, together with the finding that Col II antibodies are present in a wide array of diseases, makes their role in the pathogenesis of RA questionable. They may arise as a secondary disease perpetuating mechanism in some patients, or in turn may be an epiphenomenon secondary to generalised disturbed immunoregulation or B cell hyperreactivity, or both, that characterises these clinical conditions. PMID:3365030

  15. Autoimmune and inflammatory diseases associated with chronic myelomonocytic leukemia: A series of 26 cases and literature review.

    PubMed

    Grignano, Eric; Mekinian, Arsene; Braun, Thorsten; Liozon, Eric; Hamidou, Mohamed; Decaux, Olivier; Puéchal, Xavier; Kahn, Jean Emmanuel; Schoindre, Yoland; Rossignol, Julien; Lortholary, Olivier; Lioger, Bertrand; Hermine, Olivier; Park, Sophie; Ades, Lionel; Montestruc, François; Ricard, Laure; Gardin, Claude; Fenaux, Pierre; Fain, Olivier

    2016-08-01

    We wanted to describe the characteristics, treatment and outcome of autoimmune and inflammatory diseases (SAIDs) associated with chronic myelomonocytic leukemia (CMML), and conducted a French multicenter retrospective study and a literature review. We included 26 cases of CMML (median age 75 years, 54% female), 80% with CMML-1. CPSS score was low (0 or 1) in 75% of cases. SAIDS was systemic vasculitis in 54%. Diagnosis of the 2 diseases was concomitant in 31% cases, and CMML was diagnosed before SAIDs in 12 cases (46%). First line treatment for SAIDs consisted mostly of steroid, with 85% of response. Second-line treatment was needed in 40% cases. Six patients received hypomethylating agents, with 66% response on SAIDs. A literature review found 49 cases of CMML-associated SAIDs, in whom SAIDs was systemic vasculitis in 29% cases. Hence, vasculitis is the most frequent SAIDs associated with CMML. After initial response to steroids, recurrence and steroid-dependence were frequent. Hypomethylating agents may be interesting in this context. PMID:27337291

  16. Peripheral Nerve Ultrasonography in Chronic Inflammatory Demyelinating Polyradiculoneuropathy and Multifocal Motor Neuropathy: Correlations with Clinical and Neurophysiological Data.

    PubMed

    Merola, Aristide; Rosso, Michela; Romagnolo, Alberto; Peci, Erdita; Cocito, Dario

    2016-01-01

    Objective. This cross-sectional study analyzes the pattern of ultrasound peripheral nerve alterations in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN) at different stages of functional disability. Material and Methods. 22 CIDP and 10 MMN patients and a group of 70 healthy controls were evaluated with an ultrasound scan of the median, ulnar, peroneal, tibial, and sural nerves. Results were correlated with clinical disability scales and nerve conduction studies. Results. Patients with intermediate functional impairment showed relatively larger cross-sectional areas than subjects with either a milder (p < 0.05) or more severe impairment (p < 0.05), both in CIDP and in MMN. In addition, MMN was associated with greater side-to-side intranerve variability (p < 0.05), while higher cross-sectional areas were observed in CIDP (p < 0.05) and in nerve segments with predominantly demyelinating features (p < 0.05). Higher CSA values were observed in nerves with demyelinating features versus axonal damage (p < 0.05 for CIDP; p < 0.05 for MMN). Discussion and Conclusions. Greater extent of quantitative and qualitative US alterations was observed in patients at intermediate versus higher functional disability and in nerves with demyelinating versus axonal damage. CIDP and MMN showed differential US aspects, with greater side-to-side intranerve variability in MMN and higher cross-sectional areas in CIDP. PMID:27313890

  17. Peripheral Nerve Ultrasonography in Chronic Inflammatory Demyelinating Polyradiculoneuropathy and Multifocal Motor Neuropathy: Correlations with Clinical and Neurophysiological Data

    PubMed Central

    Merola, Aristide; Rosso, Michela; Romagnolo, Alberto; Peci, Erdita; Cocito, Dario

    2016-01-01

    Objective. This cross-sectional study analyzes the pattern of ultrasound peripheral nerve alterations in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN) at different stages of functional disability. Material and Methods. 22 CIDP and 10 MMN patients and a group of 70 healthy controls were evaluated with an ultrasound scan of the median, ulnar, peroneal, tibial, and sural nerves. Results were correlated with clinical disability scales and nerve conduction studies. Results. Patients with intermediate functional impairment showed relatively larger cross-sectional areas than subjects with either a milder (p < 0.05) or more severe impairment (p < 0.05), both in CIDP and in MMN. In addition, MMN was associated with greater side-to-side intranerve variability (p < 0.05), while higher cross-sectional areas were observed in CIDP (p < 0.05) and in nerve segments with predominantly demyelinating features (p < 0.05). Higher CSA values were observed in nerves with demyelinating features versus axonal damage (p < 0.05 for CIDP; p < 0.05 for MMN). Discussion and Conclusions. Greater extent of quantitative and qualitative US alterations was observed in patients at intermediate versus higher functional disability and in nerves with demyelinating versus axonal damage. CIDP and MMN showed differential US aspects, with greater side-to-side intranerve variability in MMN and higher cross-sectional areas in CIDP. PMID:27313890

  18. Homeostatic regulation of T cell trafficking by a B cell derived peptide is impaired in autoimmune and chronic inflammatory disease

    PubMed Central

    Apta, Bonita; Kuravi, Sahithi J.; Yates, Clara M.; Kennedy, Amy; Odedra, Arjun; Alassiri, Mohammed; Harrison, Matthew; Martin, Ashley; Barone, Francesca; Nayar, Saba; Hitchcock, Jessica R.; Cunningham, Adam F.; Raza, Karim; Filer, Andrew; Copland, David A.; Dick, Andrew D.; Robinson, Joseph; Kalia, Neena; Walker, Lucy S. K.; Buckley, Christopher D.; Nash, Gerard B.; Narendran, Parth; Rainger, G. Ed.

    2015-01-01

    During an inflammatory response, lymphocyte recruitment into tissue must be tightly controlled because dysregulated trafficking contributes to the pathogenesis of chronic disease. Here we show that during inflammation and in response to adiponectin, B cells tonically inhibit T cell trafficking by secreting a peptide (PEPITEM) proteolytically derived from 14.3.3.ζδ protein. PEPITEM binds cadherin-15 on endothelial cells, promoting synthesis and release of sphingosine-1 phosphate, which inhibits trafficking of T cells without affecting recruitment of other leukocytes. Expression of adiponectin receptors on B cells and adiponectin induced PEPITEM secretion wanes with age, implying immune senescence of the pathway. Additionally, these changes are evident in individuals with type-1-diabetes or rheumatoid arthritis, and circulating PEPITEM in patient serum is reduced compared to healthy age matched donors. In both diseases, tonic inhibition of T cell trafficking across inflamed endothelium is lost. Importantly, control of patient T cell trafficking is re-established by exogenous PEPITEM. Moreover, in animal models of peritonitis, hepatic I/R injury, Salmonella infection, Uveitis and Sjögren’s Syndrome, PEPITEM could reduce T cell recruitment into inflamed tissues. PMID:25894827

  19. Polymorphism of VEGF gene in susceptibility to chronic immune-mediated inflammatory diseases: a meta-analysis.

    PubMed

    Wei, Ni; Chen, Zijia; Xue, Zhifeng; Zhu, Yuelan

    2015-08-01

    Background Vascular endothelial growth factor (VEGF) is an important angiogenic factor and may be connected with chronic immune-mediated inflammatory diseases (IMIDs) to some extent. However, previous researches about the relationship between the +405G>C (dbSNP: rs2010963) polymorphism in VEGF gene and the risk of IMIDs are controversial and inconsistent. So we conducted this meta-analysis to assess whether the relationship between the +405G>C polymorphism in the 5'-UTR region of VEGF gene and IMID susceptibility exists. Methods Our literature search was conducted on the PubMed, Embase, Web of science, Chinese National Knowledge Infrastructure, and Chinese Biomedical databases to retrieve for eligible studies. Odds ratios as well as their 95 % confidence intervals were utilized to deduce the possible relationship. Results A total number of 5175 patients with IMIDs and 7069 healthy controls from 27 case-control studies were included. For the overall eligible data collected in our meta-analysis, there was no marked relationship between +405G>C polymorphism and the risk of IMIDs. However, subgroup analysis by ethnicity suggested that +405C allele could be a protective factor for IMIDs in Asians, whereas an opposite conclusion was drawn in Caucasians. Conclusion Thus, we may come to the conclusion that the VEGF +405G>C polymorphism could be associated with IMIDs, and the correlation might vary with ethnic groups. PMID:26007152

  20. Chronic Ethanol Feeding Modulates Inflammatory Mediators, Activation of Nuclear Factor-κB, and Responsiveness to Endotoxin in Murine Kupffer Cells and Circulating Leukocytes

    PubMed Central

    Oppermann, Elsie; Jobin, Christian; Schleucher, Elke; Marzi, Ingo

    2014-01-01

    Chronic ethanol abuse is known to increase susceptibility to infections after injury, in part, by modification of macrophage function. Several intracellular signalling mechanisms are involved in the initiation of inflammatory responses, including the nuclear factor-κB (NF-κB) pathway. In this study, we investigated the systemic and hepatic effect of chronic ethanol feeding on in vivo activation of NF-κB in NF-κBEGFP reporter gene mice. Specifically, the study focused on Kupffer cell proinflammatory cytokines IL-6 and TNF-α and activation of NF-κB after chronic ethanol feeding followed by in vitro stimulation with lipopolysaccharide (LPS). We found that chronic ethanol upregulated NF-κB activation and increased hepatic and systemic proinflammatory cytokine levels. Similarly, LPS-stimulated IL-1β release from whole blood was significantly enhanced in ethanol-fed mice. However, LPS significantly increased IL-6 and TNF-α levels. These results demonstrate that chronic ethanol feeding can improve the responsiveness of macrophage LPS-stimulated IL-6 and TNF-α production and indicate that this effect may result from ethanol-induced alterations in intracellular signalling through NF-κB. Furthermore, LPS and TNF-α stimulated the gene expression of different inflammatory mediators, in part, in a NF-κB-dependent manner. PMID:24623963

  1. Chronic ethanol feeding modulates inflammatory mediators, activation of nuclear factor-κB, and responsiveness to endotoxin in murine Kupffer cells and circulating leukocytes.

    PubMed

    Maraslioglu, Miriam; Oppermann, Elsie; Blattner, Carolin; Weber, Roxane; Henrich, Dirk; Jobin, Christian; Schleucher, Elke; Marzi, Ingo; Lehnert, Mark

    2014-01-01

    Chronic ethanol abuse is known to increase susceptibility to infections after injury, in part, by modification of macrophage function. Several intracellular signalling mechanisms are involved in the initiation of inflammatory responses, including the nuclear factor-κB (NF-κB) pathway. In this study, we investigated the systemic and hepatic effect of chronic ethanol feeding on in vivo activation of NF-κB in NF-κB(EGFP) reporter gene mice. Specifically, the study focused on Kupffer cell proinflammatory cytokines IL-6 and TNF-α and activation of NF-κB after chronic ethanol feeding followed by in vitro stimulation with lipopolysaccharide (LPS). We found that chronic ethanol upregulated NF-κB activation and increased hepatic and systemic proinflammatory cytokine levels. Similarly, LPS-stimulated IL-1 β release from whole blood was significantly enhanced in ethanol-fed mice. However, LPS significantly increased IL-6 and TNF-α levels. These results demonstrate that chronic ethanol feeding can improve the responsiveness of macrophage LPS-stimulated IL-6 and TNF-α production and indicate that this effect may result from ethanol-induced alterations in intracellular signalling through NF-κB. Furthermore, LPS and TNF-α stimulated the gene expression of different inflammatory mediators, in part, in a NF-κB-dependent manner. PMID:24623963

  2. Pro-inflammatory interleukins in middle ear effusions from atopic and non-atopic children with chronic otitis media with effusion.

    PubMed

    Zielnik-Jurkiewicz, Beata; Stankiewicz-Szymczak, Wanda

    2016-06-01

    Chronic otitis media with effusion (OME) is associated with irreversible changes in the middle ear, sometimes leading to hearing loss and abnormal language development in children. While the pathogenesis of OME is not fully understood, inflammatory and allergic factors are thought to be involved. The study aimed to investigate the role of cytokines in the local development of chronic OME, and assess differences in the cytokine profiles between atopic and non-atopic children. 84 atopic and non-atopic children with chronic OME (mean age of 6 years 7 months) were studied. Age-matched children with hypertrophy of the adenoids and Eustachian tube dysfunction served as the control group. The number of past acute otitis media (AOM) episodes, their age, and the type of effusion were recorded for all children. Pro-inflammatory cytokine concentrations (TNF-α, IL-1β, IL-6 and IL-8) were determined and the presence of pathogenic bacteria in the patients' effusions was examined. High concentrations of TNF-α, IL-1β, IL-6 and IL-8 were found in the effusions in all children with chronic OME, with the highest levels observed in the non-atopic group. The atopic group showed persistently high IL-1β levels, while in the non-atopic children, IL-1β and TNF-α levels positively correlated with the patient's age and the number of past AOM episodes. Pathogenic bacteria were more frequently isolated from effusions in non-atopic children. In both atopic and non-atopic children, pro-inflammatory cytokines are found at high concentrations. This argues in favor of instituting anti-inflammatory management for treating OME, regardless of atopy. PMID:26078091

  3. Provenance Store Evaluation

    SciTech Connect

    Paulson, Patrick R.; Gibson, Tara D.; Schuchardt, Karen L.; Stephan, Eric G.

    2008-03-01

    Requirements for the provenance store and access API are developed. Existing RDF stores and APIs are evaluated against the requirements and performance benchmarks. The team’s conclusion is to use MySQL as a database backend, with a possible move to Oracle in the near-term future. Both Jena and Sesame’s APIs will be supported, but new code will use the Jena API

  4. Fibronectin type III domain containing 5 expression in skeletal muscle in chronic heart failure—relevance of inflammatory cytokines

    PubMed Central

    Matsuo, Yae; Gleitsmann, Konstanze; Mangner, Norman; Werner, Sarah; Fischer, Tina; Bowen, T Scott; Kricke, Angela; Matsumoto, Yasuharu; Kurabayashi, Masahiko; Schuler, Gerhard; Linke, Axel; Adams, Volker

    2015-01-01

    Background Chronic heart failure (CHF) is commonly associated with muscle atrophy and increased inflammation. Irisin, a myokine proteolytically processed by the fibronectin type III domain containing 5 (FNDC5) gene and suggested to be Peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α activated, modulates the browning of adipocytes and is related to muscle mass. Therefore, we investigated whether skeletal muscle FNDC5 expression in CHF was reduced and if this was mediated by inflammatory cytokines and/or angiotensin II (Ang-II). Methods Skeletal muscle FNDC5 mRNA/protein and PGC-1α mRNA expression (arbitrary units) were analysed in: (i) rats with ischemic cardiomyopathy; (ii) mice injected with tumour necrosis factor-α (TNF-α) (24 h); (iii) mice infused with Ang-II (4 weeks); and (iv) C2C12 myotubes exposed to recombinant cytokines or Ang-II. Circulating TNF-α, Ang-II, and irisin was measured by ELISA. Results Ischemic cardiomyopathy reduced significantly FNDC5 protein (1.3 ± 0.2 vs. 0.5 ± 0.1) and PGC-1α mRNA expression (8.2 ± 1.5 vs. 4.7 ± 0.7). In vivo TNF-α and Ang-II reduced FNDC5 protein expression by 28% and 45%, respectively. Incubation of myotubes with TNF-α, interleukin-1ß, or TNF-α/interleukin-1ß reduced FNDC5 protein expression by 47%, 37%, or 57%, respectively, whereas Ang-II had no effect. PGC-1α was linearly correlated to FNDC5 in all conditions. In CHF, animals circulating TNF-α and Ang-II were significantly increased, whereas irisin was significantly reduced. A negative correlation between circulating TNF-α and irisin was evident. Conclusion A reduced expression of skeletal muscle FNDC5 in ischemic cardiomyopathy is likely modulated by inflammatory cytokines and/or Ang-II via the down-regulation of PGC-1α. This may act as a protective mechanism either by slowing the browning of adipocytes and preserving energy homeostasis or by regulating muscle atrophy. PMID:26136413

  5. Points to consider for reporting, screening for and preventing selected comorbidities in chronic inflammatory rheumatic diseases in daily practice: a EULAR initiative.

    PubMed

    Baillet, Athan; Gossec, Laure; Carmona, Loreto; Wit, Maarten de; van Eijk-Hustings, Yvonne; Bertheussen, Heidi; Alison, Kent; Toft, Mette; Kouloumas, Marios; Ferreira, Ricardo J O; Oliver, Susan; Rubbert-Roth, Andrea; van Assen, Sander; Dixon, William G; Finckh, Axel; Zink, Angela; Kremer, Joel; Kvien, Tore K; Nurmohamed, Michael; van der Heijde, Desirée; Dougados, Maxime

    2016-06-01

    In chronic inflammatory rheumatic diseases, comorbidities such as cardiovascular diseases and infections are suboptimally prevented, screened for and managed. The objective of this European League Against Rheumatism (EULAR) initiative was to propose points to consider to collect comorbidities in patients with chronic inflammatory rheumatic diseases. We also aimed to develop a pragmatic reporting form to foster the implementation of the points to consider. In accordance with the EULAR Standardised Operating Procedures, the process comprised (1) a systematic literature review of existing recommendations on reporting, screening for or preventing six selected comorbidities: ischaemic cardiovascular diseases, malignancies, infections, gastrointestinal diseases, osteoporosis and depression and (2) a consensus process involving 21 experts (ie, rheumatologists, patients, health professionals). Recommendations on how to treat the comorbidities were not included in the document as they vary across countries. The literature review retrieved 42 articles, most of which were recommendations for reporting or screening for comorbidities in the general population. The consensus process led to three overarching principles and 15 points to consider, related to the six comorbidities, with three sections: (1) reporting (ie, occurrence of the comorbidity and current treatments); (2) screening for disease (eg, mammography) or for risk factors (eg, smoking) and (3) prevention (eg, vaccination). A reporting form (93 questions) corresponding to a practical application of the points to consider was developed. Using an evidence-based approach followed by expert consensus, this EULAR initiative aims to improve the reporting and prevention of comorbidities in chronic inflammatory rheumatic diseases. Next steps include dissemination and implementation. PMID:26984008

  6. Anti-inflammatory effect of glycosaminoglycan derived from Gryllus bimaculatus (a type of cricket, insect) on adjuvant-treated chronic arthritis rat model.

    PubMed

    Ahn, Mi Young; Han, Jea Woong; Hwang, Jae Sam; Yun, Eun Young; Lee, Byung Mu

    2014-01-01

    Anti-inflammatory effects of glycosaminoglycan (GAG) derived from cricket (Gryllus bimaculatus, Gb) were investigated in a complete Freund's adjuvant (CFA)-treated chronic arthritic rat model. This GAG produced a significant anti-edema effect as evidenced by inhibition of C-reactive protein (CRP) and rheumatoid factor, and interfered with atherogenesis by reducing proinflammatory cytokine levels of (1) vascular endothelial growth factor (VEGF) production in human umbilical vein endothelial cells (HUVEC), (2) interleukin-6, (3) prostaglandin E2-stimulated lipopolysaccharide in RAW 264.7 cells, and (4) tumor necrosis factor (TNF)-α production in normal splenocytes, in a dose-dependent manner. This GAG was also found to induce nitric oxide (NO) production in HUVEC cells and elevated endothelial nitric oxide synthase (eNOS) activity levels. Histological findings demonstrated the fifth lumbar vertebrae (LV) dorsal root ganglion, which was linked to the paw treated with Gb GAG, was repaired against CFA-induced cartilage destruction. Further, combined indomethacin (5 mg/kg)-Gb GAG (10 mg/kg) inhibited more effectively CFA-induced paw edema at 3 h and 2 or 3 d after treatment to levels comparable to only the anti-inflammatory drug indomethacin. Ultraviolet (UV)-irritated skin inflammation also downregulated nuclear factor κB (NFκB) activity in transfected HaCaT cells. Data suggest that the anti-inflammatory effects of GAG obtained from cricket (Gb) may be useful for treatment of inflammatory diseases including chronic arthritis. PMID:25343284

  7. Therapeutic Helminth Infection of Macaques with Idiopathic Chronic Diarrhea Alters the Inflammatory Signature and Mucosal Microbiota of the Colon

    PubMed Central

    Broadhurst, Mara Jana; Ardeshir, Amir; Kanwar, Bittoo; Mirpuri, Julie; Gundra, Uma Mahesh; Leung, Jacqueline M.; Wiens, Kirsten E.; Vujkovic-Cvijin, Ivan; Kim, Charlie C.; Yarovinsky, Felix; McCune, Joseph M.; Loke, P'ng

    2012-01-01

    Idiopathic chronic diarrhea (ICD) is a leading cause of morbidity amongst rhesus monkeys kept in captivity. Here, we show that exposure of affected animals to the whipworm Trichuris trichiura led to clinical improvement in fecal consistency, accompanied by weight gain, in four out of the five treated monkeys. By flow cytometry analysis of pinch biopsies collected during colonoscopies before and after treatment, we found an induction of a mucosal TH2 response following helminth treatment that was associated with a decrease in activated CD4+ Ki67+ cells. In parallel, expression profiling with oligonucleotide microarrays and real-time PCR analysis revealed reductions in TH1-type inflammatory gene expression and increased expression of genes associated with IgE signaling, mast cell activation, eosinophil recruitment, alternative activation of macrophages, and worm expulsion. By quantifying bacterial 16S rRNA in pinch biopsies using real-time PCR analysis, we found reduced bacterial attachment to the intestinal mucosa post-treatment. Finally, deep sequencing of bacterial 16S rRNA revealed changes to the composition of microbial communities attached to the intestinal mucosa following helminth treatment. Thus, the genus Streptophyta of the phylum Cyanobacteria was vastly increased in abundance in three out of five ICD monkeys relative to healthy controls, but was reduced to control levels post-treatment; by contrast, the phylum Tenericutes was expanded post-treatment. These findings suggest that helminth treatment in primates can ameliorate colitis by restoring mucosal barrier functions and reducing overall bacterial attachment, and also by altering the communities of attached bacteria. These results also define ICD in monkeys as a tractable preclinical model for ulcerative colitis in which these effects can be further investigated. PMID:23166490

  8. Inflammatory Markers and the Risk of Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis.

    PubMed

    Su, Bin; Liu, Tiansheng; Fan, Haojun; Chen, Feng; Ding, Hui; Wu, Zhouwei; Wang, Hongwu; Hou, Shike

    2016-01-01

    Systemic inflammatory factors are inconsistently associated with the pathogenesis of chronic obstructive pulmonary disease (COPD). We conducted a systematic review and meta-analysis to summarize the evidence supporting the association between systemic inflammation and the risk of COPD. Pertinent studies were retrieved from PubMed, EmBase, and the Cochrane Library until April 2015. A random-effects model was used to process the data, and the analysis was further stratified by factors affecting these associations. Sensitivity analyses for publication bias were performed. We included 24 observational studies reporting data on 10,677 COPD patients and 28,660 controls. Overall, we noted that COPD was associated with elevated serum CRP (SMD: 1.21; 95%CI: 0.92-1.50; P < 0.001), leukocytes (SMD: 1.07; 95%: 0.25-1.88; P = 0.010), IL-6 (SMD: 0.90; 95%CI: 0.48-1.31; P < 0.001), IL-8 (SMD: 2.34; 95%CI: 0.69-4.00; P = 0.006), and fibrinogen levels (SMD: 0.87; 95%CI: 0.44-1.31; P < 0.001) when compared with control. However, COPD was not significantly associated with TNF-α levels when compared with control (SMD: 0.60; 95%CI: -0.46 to 1.67; P = 0.266). Our findings suggested that COPD was associated with elevated serum CRP, leukocytes, IL-6, IL-8, and fibrinogen, without any significant relationship with TNF-α. PMID:27104349

  9. Inflammatory Markers and the Risk of Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis

    PubMed Central

    Su, Bin; Liu, Tiansheng; Fan, Haojun; Chen, Feng; Ding, Hui; Wu, Zhouwei; Wang, Hongwu; Hou, Shike

    2016-01-01

    Systemic inflammatory factors are inconsistently associated with the pathogenesis of chronic obstructive pulmonary disease (COPD). We conducted a systematic review and meta-analysis to summarize the evidence supporting the association between systemic inflammation and the risk of COPD. Pertinent studies were retrieved from PubMed, EmBase, and the Cochrane Library until April 2015. A random-effects model was used to process the data, and the analysis was further stratified by factors affecting these associations. Sensitivity analyses for publication bias were performed. We included 24 observational studies reporting data on 10,677 COPD patients and 28,660 controls. Overall, we noted that COPD was associated with elevated serum CRP (SMD: 1.21; 95%CI: 0.92–1.50; P < 0.001), leukocytes (SMD: 1.07; 95%: 0.25–1.88; P = 0.010), IL-6 (SMD: 0.90; 95%CI: 0.48–1.31; P < 0.001), IL-8 (SMD: 2.34; 95%CI: 0.69–4.00; P = 0.006), and fibrinogen levels (SMD: 0.87; 95%CI: 0.44–1.31; P < 0.001) when compared with control. However, COPD was not significantly associated with TNF-α levels when compared with control (SMD: 0.60; 95%CI: -0.46 to 1.67; P = 0.266). Our findings suggested that COPD was associated with elevated serum CRP, leukocytes, IL-6, IL-8, and fibrinogen, without any significant relationship with TNF-α. PMID:27104349

  10. Conducting processes in simulated chronic inflammatory demyelinating polyneuropathy at 20°C-42°C.

    PubMed

    Stephanova, D I; Daskalova, M; Mladenov, M

    2015-03-01

    Decreased conducting processes leading usually to conduction block and increased weakness of limbs during cold (cold paresis) or warmth (heat paresis) have been reported in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). To explore the mechanisms of these symptoms, the effects of temperature (from 20°C to 42°C) on nodal action potentials and their current kinetics in previously simulated case of 70% CIDP are investigated, using our temperature dependent multi-layered model of the myelinated human motor nerve fiber. The results show that potential amplitudes have a bifid form at 20°C. As in the normal case, for the CIDP case, the nodal action potentials are determined mainly by the nodal sodium currents (I Na ) for the temperature range of 20-39°C, as the contribution of nodal fast and slow potassium currents (I Kf and I Ks ) to the total ionic current (Ii) is negligible. Also, the contribution of I Kf and I Ks to the membrane repolarization is enhanced at temperatures higher than 39°C. However, in the temperature range of 20-42°C, all potential parameters in the CIDP case, except for the conduction block during hyperthermia (≥ 40°C) which is again at 45°C, worsen: (i) conduction velocities and potential amplitudes are decreased; (ii) afterpotentials and threshold stimulus currents for the potential generation are increased; (iii) the current kinetics of action potentials is slowed and (iv) the conduction block during hypothermia (≤ 25°C) is at temperatures lower than 20°C. These potential parameters are more altered during hyperthermia and are most altered during hypothermia. The present results suggest that the conducting processes in patients with CIDP are in higher risk during hypothermia than hyperthermia. PMID:25597276

  11. Curcumin protects against radiation-induced acute and chronic cutaneous toxicity in mice and decreases mRNA expression of inflammatory and fibrogenic cytokines

    SciTech Connect

    Okunieff, Paul . E-mail: paul_okunieff@urmc.rochester.edu; Xu Jianhua; Hu Dongping; Liu Weimin; Zhang Lurong; Morrow, Gary; Pentland, Alice; Ryan, Julie L.; Ding, Ivan M.D.

    2006-07-01

    Purpose: To determine whether curcumin ameliorates acute and chronic radiation skin toxicity and to examine the expression of inflammatory cytokines (interleukin [IL]-1, IL-6, IL-18, IL-1Ra, tumor necrosis factor [TNF]-{alpha}, and lymphotoxin-{beta}) or fibrogenic cytokines (transforming growth factor [TGF]-{beta}) during the same acute and chronic phases. Methods and Materials: Curcumin was given intragastrically or intraperitoneally to C3H/HeN mice either: 5 days before radiation; 5 days after radiation; or both 5 days before and 5 days after radiation. The cutaneous damage was assessed at 15-21 days (acute) and 90 days (chronic) after a single 50 Gy radiation dose was given to the hind leg. Skin and muscle tissues were collected for measurement of cytokine mRNA. Results: Curcumin, administered before or after radiation, markedly reduced acute and chronic skin toxicity in mice (p < 0.05). Additionally, curcumin significantly decreased mRNA expression of early responding cytokines (IL-1 IL-6, IL-18, TNF-{alpha}, and lymphotoxin-{beta}) and the fibrogenic cytokine, TGF-{beta}, in cutaneous tissues at 21 days postradiation. Conclusion: Curcumin has a protective effect on radiation-induced cutaneous damage in mice, which is characterized by a downregulation of both inflammatory and fibrogenic cytokines in irradiated skin and muscle, particularly in the early phase after radiation. These results may provide the molecular basis for the application of curcumin in clinical radiation therapy.

  12. Effect of oral administration involving a probiotic strain of Lactobacillus reuteri on pro-inflammatory cytokine response in patients with chronic periodontitis.

    PubMed

    Szkaradkiewicz, Anna K; Stopa, Janina; Karpiński, Tomasz M

    2014-12-01

    This study aimed at evaluation of pro-inflammatory cytokine response (TNF-α, IL-1β and IL-17) in patients with chronic periodontitis administered per os with a probiotic strain of Lactobacillus reuteri. In the 38 adult patients with moderate chronic periodontitis, professional cleaning of teeth was performed. Two weeks after performing the oral hygienization procedures, clinical examination permitted to distinguish a group of 24 patients (Group 1) in whom treatment with probiotic tablets containing L. reuteri strain, producing hydrogen peroxide (Prodentis), was conducted. In the remaining 14 patients, no probiotic tablet treatment was applied (the control group; Group 2). From all patients in two terms, gingival crevicular fluid (GCF) was sampled from all periodontal pockets. Estimation of TNF-α, IL-lβ and IL-17 in GCF was performed using the ELISA method. After completion of the therapy with probiotic tablets, 18 (75%) of the patients of Group 1 have manifested a significant decrease in levels of studied pro-inflammatory cytokines (TNF-α, IL-1β and IL-17). In parallel, we have detected an improvement of clinical indices [sulcus bleeding index (SBI), periodontal probing depth (PPD), clinical attachment level (CAL)]. At individuals of Group 2 levels of studies, pro-inflammatory cytokines and clinical indices (SBI, PPD, CAL) were significantly higher than in Group 1. Results obtained in this study indicate that application of oral treatment with tablets containing probiotic strain of L. reuteri induces in most patients with chronic periodontitis a significant reduction of pro-inflammatory cytokine response and improvement of clinical parameters (SBI, PPD, CAL). Therefore, such an effect may result in a reduced activity of the morbid process. PMID:24509697

  13. Chronic inflammatory polyneuropathy

    MedlinePlus

    ... Tests may include: Electromyography ( EMG ) Nerve conduction tests Nerve biopsy Spinal tap Blood tests may be done to look for specific proteins that are causing the immune attack on the nerves Which other tests are done depends on the ...

  14. Chronic Gamma-Irradiation Induces a Dose-Rate-Dependent Pro-inflammatory Response and Associated Loss of Function in Human Umbilical Vein Endothelial Cells.

    PubMed

    Ebrahimian, T; Le Gallic, C; Stefani, J; Dublineau, I; Yentrapalli, R; Harms-Ringdahl, M; Haghdoost, S

    2015-04-01

    A central question in radiation protection research is dose and dose-rate relationship for radiation-induced cardiovascular diseases. The response of endothelial cells to different low dose rates may contribute to help estimate risks for cardiovascular diseases by providing mechanistic understanding. In this study we investigated whether chronic low-dose-rate radiation exposure had an effect on the inflammatory response of endothelial cells and their function. Human umbilical vein endothelial cells (HUVECs) were chronically exposed to radiation at a dose of 1.4 mGy/h or 4.1 mGy/h for 1, 3, 6 or 10 weeks. We determined the pro-inflammatory profile of HUVECs before and during radiation exposure, and investigated the functional consequences of this radiation exposure by measuring their capacity to form vascular networks in matrigel. Expression levels of adhesion molecules such as E-selectin, ICAM-1 and VCAM-1, and the release of pro-inflammatory cytokines such as MCP-1, IL-6 and TNF-α were analyzed. When a total dose of 2 Gy was given at a rate of 4.1 mGy/h, we observed an increase in IL-6 and MCP-1 release into the cell culture media, but this was not observed at 1.4 mGy/h. The increase in the inflammatory profile induced at the dose rate of 4.1 mGy/h was also correlated with a decrease in the capacity of the HUVECs to form a vascular network in matrigel. Our results suggest that dose rate is an important parameter in the alteration of HUVEC inflammatory profile and function. PMID:25807321

  15. Colocalization of insulin-like growth factor-1 receptor and T type Cav3.2 channel in dorsal root ganglia in chronic inflammatory pain mouse model.

    PubMed

    Lin, Si-Fang; Yu, Xiao-Lu; Wang, Bing; Zhang, Ya-Jun; Sun, Yan-Gang; Liu, Xing-Jun

    2016-07-01

    Insulin-like growth factor-1 (IGF-1) is a neurotrophic factor and plays important roles in the nervous system. Increasing evidence supports that IGF-1 contributes to pain hypersensitivity through its insulin-like growth factor-1 receptor (IGF-1R) by activating IGF-1R/Akt or MAPK signaling pathways, whereas T-type Cav3.2 channel can facilitate and amplify pain signals originating from the sensory periphery. A recent study showed that activated IGF-1R can increase T-type Cav3.2 channel currents and further activate the G protein-dependent PKCα pathway to contribute to inflammatory pain sensitivity. However, the colocalization of IGF-1R and Cav3.2 in mouse dorsal root ganglion (DRG) under chronic inflammatory pain conditions remains elusive. In this study, we investigated changes in the expression of IGF-1R and the Cav3.2 channel, and their colocalization in mouse DRGs in chronic inflammatory pain condition (induced by complete Freund's adjuvant intraplanter injection) using real-time RT-PCR and immunohistochemistry approaches to confirm that Cav3.2 channel can mediate pain facilitation following IGF-1/IGF-1R signaling. We found that IGF-1R was expressed extensively in DRG neurons including small-, medium-, and large-sized neurons, whereas Cav3.2 channel was expressed exclusively in small-sized DRG neurons of naive mice. Expression of Cav3.2, but not IGF-1R, and colocalization of Cav3.2 and IGF-1R were increased in lumbar (L)4-L6 primary sensory neurons in DRGs of mice in chronic inflammatory pain. Moreover, the increased colocalization of IGF-1R and Cav3.2 is exclusively localized in small- and medium-sized primary sensory neurons. Our findings provided morphological evidence that T-type Cav3.2 channel, at least partially, mediates the pain facilitation of IGF-1/IGF-1R signaling in chronic inflammatory pain condition. PMID:27213932

  16. Evaluation of chemical mediators and cellular response during acute and chronic gut inflammatory response induced by dextran sodium sulfate in mice.

    PubMed

    Bento, Allisson Freire; Leite, Daniela Ferraz Pereira; Marcon, Rodrigo; Claudino, Rafaela Franco; Dutra, Rafael Cypriano; Cola, Maíra; Martini, Alessandra Cadete; Calixto, João B

    2012-12-01

    Inflammatory bowel disease (IBD) affects millions of people worldwide but its pathophysiology remains unclear. Therefore, experimental models of colitis have contributed crucially for the understanding of IBD, and also in the investigations for effective therapies. Herein we investigated the kinetics of inflammatory mediator production and cell infiltration during acute and chronic dextran sodium sulfate (DSS)-induced colitis. The induction phases with DSS were characterized by severe disease activity with massive colonic polymorphonuclear infiltration and increased levels of tumor necrosis factor-α (TNF-α), keratinocyte-derived chemokine (CXCL1/KC), interleukin (IL)-17 and vascular adhesion molecule-1 (VCAM-1). Interestingly, in the recovery periods, we found marked increase of anti-inflammatory mediators IL-10, IL-4, transforming growth factor-β (TGF-β) and cyclooxygenase 2 (COX-2) that seems be essential for the resolution of intestinal inflammation. Furthermore, nuclear factor κB (NFκB) and regulatory T cell marker forkhead box P3 (FoxP3) were increased gradually during experimental colitis, demonstrating a discrepant profile response and evident immune disbalance in the chronic phase of intestinal mucosal inflammation. Taken together, these results provide valuable information for studies on DSS-induced colitis and especially for the identification of biomarkers that predict disease course and possible therapeutic interventions. PMID:23000912

  17. Provenance for Environmental Cyberenvironments

    NASA Astrophysics Data System (ADS)

    Futrelle, J.

    2006-12-01

    Scientific collaboration is a complex distributed process that spans disciplinary, organizational, and spatiotemporal boundaries. As information technology (IT) is deployed in scientific communities, new techniques are required to manage these complex processes so that the digital artifacts associated with scientific knowledge can be used as effectively as possible. Cyberenvironments (CE) propose to extend current IT infrastructure to support distributed, collaborative work, comprising online collaboration tools, distributed data management, distributed processing, and social networking analysis. The Environmental Cyberinfrastructure Demonstrator (ECID) project at the National Center for Supercomputing Applications (NCSA) is exploring cyberenvironment directions for environmental research, motivated in particular by the requirements being identified through the NSF's CLEANER/CUASHI/WATERS environmental observatory planning activities. These requirements entail providing integrated access to an evolving set of community sensor networks, data collections, models, analysis tools, literature, and community members, and tracking the relationships between them. The metadata and provenance information required to support resource discovery and information fusion to support new scientific endeavors is anticipated to come from a variety of sources including human inputs, direct reporting from individual tools, and inferences from observations of human and system activities and to evolve over time. At NCSA, we have been developing a lightweight, distributed infrastructure for managing metadata and provenance information and, through ECID, applying it in support of environmental observatory scenarios. This poster will provide an overview of the technical infrastructure being created, describe the set of tools and types of information being managed in ECID, and outline concepts such as sharing of best-practice workflows and community model validation that would leverage this

  18. Neutrophilic inflammatory response and oxidative stress in premenopausal women chronically exposed to indoor air pollution from biomass burning.

    PubMed

    Banerjee, Anirban; Mondal, Nandan Kumar; Das, Debangshu; Ray, Manas Ranjan

    2012-04-01

    , the levels of neutrophil activation and inflammation markers were positively associated with generation of ROS and negatively with SOD, indicating a role of oxidative stress in mediating neutrophilic inflammatory response following chronic inhalation of biomass smoke. PMID:21769440

  19. Vaccinations in adults with chronic inflammatory joint disease: Immunization schedule and recommendations for patients taking synthetic or biological disease-modifying antirheumatic drugs.

    PubMed

    Morel, Jacques; Czitrom, Séverine Guillaume; Mallick, Auriane; Sellam, Jérémie; Sibilia, Jean

    2016-03-01

    The risk of infection associated with autoimmune diseases is further increased by the use of biotherapies. Recommendations to minimize this risk include administering the full complement of vaccines on the standard immunization schedule, as well as the pneumococcal and influenza vaccines. Adults with chronic inflammatory joint disease (IJD) may receive a 13-valent pneumococcal conjugate vaccine, as well as a live attenuated vaccine against recurrent herpes zoster, recently licensed by European regulatory authorities. Live attenuated vaccines can be given only after an interval without immunosuppressant and/or glucocorticoid therapy. The effectiveness of vaccines, as assessed based on titers of protective antibodies, varies across vaccine types and disease-modifying antirheumatic drugs (DMARDs). Thus, methotrexate and rituximab are usually associated with decreased vaccine responses. The risks associated with vaccines are often considerably exaggerated by the media, which serve lobbies opposed to immunizations and make some patients reluctant to accept immunizations. Increasing immunization coverage may diminish the risk of treatment-related infections. A physician visit dedicated specifically to detecting comorbidities in patients with chronic IJD may result in improved immunization coverage. In this review, we discuss immunizations for adults with chronic IJD based on the treatments used, as well as immunization coverage. Many questions remain unanswered and warrant investigation by studies coordinated by the French networks IREIVAC (Innovative clinical research network in vaccinology) and IMIDIATE (Immune-Mediated Inflammatory Disease Alliance for Translational and Clinical Research). PMID:26453106

  20. Chronic Pancreatitis and Systemic Inflammatory Response Syndrome Prevent Impact of Chemotherapy with Gemcitabine in a Genetically Engineered Mouse Model of Pancreatic Cancer12

    PubMed Central

    Knoop, Richard F.; Sparn, Moritz; Waldmann, Jens; Plassmeier, Lars; Bartsch, Detlef K.; Lauth, Matthias; Hudemann, Christoph; Fendrich, Volker

    2014-01-01

    BACKGROUND AND AIMS BACKGROUND AND AIMSGemcitabine is the standard therapy for patients with pancreatic cancer with metastatic disease. Patients with metastatic pancreatic cancer presenting with increased values of C-reactive protein do not respond to gemcitabine. So far, no studies have evaluated the correlation between chronic pancreatitis, systemic inflammatory response syndrome, and the loss of chemotherapeutic benefit. METHODS Pdx-1-Cre;LSL-KrasG12D/+;LSL-Trp53R172H/+ mice were assigned into four groups: 1) Sixteen animals received a daily intraperitoneal injection of caerulein from their ninth week of life on. 2) Sixteen mice were additionally given gemcitabine. 3) Twelve animals received gemcitabine only. 4) Saline-treated control group. Furthermore, human Paca44 pancreatic ductal adenocarcinoma cells were seeded and cultured in 0.5% FBS containing growth medium plus/minus 1 μM gemcitabine plus/minus recombinant human interleukin (IL)-6. RESULTS Induced systemic inflammatory response syndrome and a mild chronic pancreatitis diminished the beneficial effects of gemcitabine upon median overall survival. In median, the monogemcitabine group survived 191 days, whereas the caerulein-mono group survived 114, the control group 121, and the caerulein gemcitabine group 127 days (P < .05). In vitro, the induction of STAT3 phosphorylation by recombinant human IL-6 promoted pancreatic ductal adenocarcinoma cell survival during gemcitabine treatment. CONCLUSION We could demonstrate for the first time that an improvement in median overall survival with gemcitabine is significantly abolished by a persistent mild chronic pancreatitis and a systemic inflammatory response syndrome. In particular, the inflammation biomarkers C-reactive protein, IL-6, and IL-1α could indicate the prognostic benefit of gemcitabine chemotherapy and should now be tested in prospective patient-controlled trials. PMID:24953430

  1. AB099. The anti-inflammatory and anti-microbial effects of the novel herbal formulation (WSY-1075) on chronic bacterial prostatitis rat model

    PubMed Central

    Bae, Woong Jin; Bashraheel, Fahad; Choi, Sae Woong; Kim, Su Jin; Kim, Sae Woong; Yoon, Byung Il

    2016-01-01

    Objective The aim of this study was to investigate the anti-inflammatory and anti-microbial effects of a new herbal formula (WSY-1075) in a chronic bacterial prostatitis rat model. Methods Thirty two male Wistar rats were used in the study. Experimental chronic bacterial prostatitis was induced by instillation of bacterial suspension (Escherichia coli 108 per mL) into the prostatic urethra. Animals were followed for 4 weeks. After the induction of prostatitis, the rats were randomly divided into one of four treatment groups: control (n=8), ciprofloxacin (n=8), WSY-1075 (400 mg/kg) (n=8), and WSY-1075 (400 mg/kg) + ciprofloxacin (n=8). After 4 weeks of treatment, the prostatic pro-inflammatory cytokine [tumor necrosis factor-α, interleukin (IL)-6, and IL-8] levels, anti-oxidant effects (superoxide dismutase) and histological findings were noted. Results The use of ciprofloxacin, WSY-1075, and WSY-1075 with ciprofloxacin showed statistically significant decreases in bacterial growth and improvements in the reduction of prostatic inflammation compared with the control group (P<0.05). The WSY-1075 with ciprofloxacin group showed a statistically significant decrease in bacterial growth and improvement in prostatic inflammation compared with the ciprofloxacin group (P<0.05). Conclusions These results suggest that WSY-1075 may have anti-inflammatory and antimicrobial effects, as well as a synergistic effect with ciprofloxacin. Therefore, we suggest that the combination of WSY-1075 and ciprofloxacin may be effective in treating chronic bacterial prostatitis to obtain a higher rate of treatment success.

  2. Basaltic island sand provenance

    SciTech Connect

    Marsaglia, K.M. . Dept. of Geological Sciences)

    1992-01-01

    The Hawaiian Islands are an ideal location to study basaltic sand provenance in that they are a series of progressively older basaltic shield volcanoes with arid to humid microclimates. Sixty-two sand samples were collected from beaches on the islands of Hawaii, Maui, Oahu and Kauai and petrographically analyzed. The major sand components are calcareous bioclasts, volcanic lithic fragments, and monomineralic grains of dense minerals and plagioclase. Proportions of these components vary from island to island, with bioclastic end members being more prevalent on older islands exhibiting well-developed fringing reef systems and volcanic end members more prevalent on younger, volcanically active islands. Climatic variations across the island of Hawaii are reflected in the percentage of weathered detritus, which is greater on the wetter, northern side of the island. The groundmass of glassy, basaltic lithics is predominantly black tachylite, with lesser brown sideromelane; microlitic and lathwork textures are more common than holohyaline vitric textures. Other common basaltic volcanic lithic fragments are holocrystalline aggregates of silt-sized pyroxene or olivine, opaque minerals and plagioclase. Sands derived from alkalic lavas are texturally and compositionally indistinguishable from sands derived from tholeiitic lavas. Although Hawaiian basaltic sands overlap in composition with magmatic arc-derived sands in terms of their relative QFL, QmPK and LmLvLs percentages, they are dissimilar in that they lack felsic components and are more enriched in lathwork volcanic lithic fragments, holocrystalline volcanic lithic fragments, and dense minerals.

  3. A Possible Change Process of Inflammatory Cytokines in the Prolonged Chronic Stress and Its Ultimate Implications for Health

    PubMed Central

    Tian, Rui; Hou, Gonglin; Li, Dan; Yuan, Ti-Fei

    2014-01-01

    Sustained stress triggers series of changes in the brain and the body. At the early stage of stress, the activated hypothalamus-pituitary-adrenal (HPA) axis and sympathetic nervous system (SNS) axis can upregulate the levels of glucocorticoid (GCs) and catecholamines (CAs), respectively, and then they in turn inhibit the secretion of proinflammatory cytokines directly or indirectly while promoting the secretion of anti-inflammatory cytokines. At the prolonged stage, the sustained activated HPA demonstrates cortisol-resistance. At the same time, the inflammation related transcription pathway, such as nuclear-factor kappa-B (NF-κB) signaling, may be inhibited. Additionally, the inflammatory cytokines mediate a negative feedback regulation on themselves. Collectively, these regulations may increase the proinflammatory cytokines while decreasing the anti-inflammatory cytokines. This may further activate NF-κB and increase the proinflammation cytokines, which in turn reduce the inflammatory responses, contributing to various diseases. PMID:24995360

  4. Chronic cholecystitis

    MedlinePlus

    ... foods may relieve symptoms in people. However, the benefit of a low-fat diet has not been proven. Alternative Names Cholecystitis - chronic Images Cholecystitis, CT scan Cholecystitis, cholangiogram Cholecystolithiasis Gallstones, cholangiogram Cholecystogram References Wang ...

  5. Post-chikungunya chronic inflammatory rheumatism: results from a retrospective follow-up study of 283 adult and child cases in La Virginia, Risaralda, Colombia

    PubMed Central

    Rodriguez-Morales, Alfonso J.; Gil-Restrepo, Andrés F.; Ramírez-Jaramillo, Valeria; Montoya-Arias, Cindy P.; Acevedo-Mendoza, Wilmer F.; Bedoya-Arias, Juan E.; Chica-Quintero, Laura A.; Murillo-García, David R.; García-Robledo, Juan E.; Castrillón-Spitia, Juan D.; Londoño, Jose J.; Bedoya-Rendón, Hector D.; Cárdenas-Pérez, Javier de Jesús; Cardona-Ospina, Jaime A.; Lagos-Grisales, Guillermo J.

    2016-01-01

    Objective: There are limited studies in Latin America regarding the chronic consequences of the Chikungunya virus (CHIK), such as post-CHIK chronic inflammatory rheumatism (pCHIK-CIR). We assessed the largest cohort so far of pCHIK-CIR in Latin America, at the municipality of La Virginia, Risaralda, a new endemic area of CHIK in Colombia. Methods: We conducted a cohort retrospective study in Colombia of 283 patients diagnosed with CHIK that persisted with pCHIK-CIR after a minimum of 6 weeks and up to a maximum of 26.1 weeks. pCHIK cases were identified according to validated criteria via telephone. Results: Of the total CHIK-infected subjects, 152 (53.7%) reported persistent rheumatological symptoms (pCHIK-CIR). All of these patients reported joint pains (chronic polyarthralgia, pCHIK-CPA), 49.5% morning stiffness, 40.6% joint edema, and 16.6% joint redness. Of all patients, 19.4% required and attended for care prior to the current study assessment (1.4% consulting rheumatologists). Significant differences in the frequency were observed according to age groups and gender. Patients aged >40 years old required more medical attention (39.5%) than those ≤40 years-old (12.1%) (RR=4.748, 95%CI 2.550-8.840). Conclusions: According to our results, at least half of the patients with CHIK developed chronic rheumatologic sequelae, and from those with pCHIK-CPA, nearly half presented clinical symptoms consistent with inflammatory forms of the disease. These results support previous estimates obtained from pooled data of studies in La Reunion (France) and India and are consistent with the results published previously from other Colombian cohorts in Venadillo (Tolima) and Since (Sucre). PMID:27081477

  6. Anti-inflammatory and pro-angiogenic effects of beta blockers in a canine model of chronic ischemic cardiomyopathy: comparison between carvedilol and metoprolol

    PubMed Central

    Le, D. Elizabeth; Pascotto, Marco; Leong-Poi, Howard; Sari, Ibrahim; Micari, Antonio; Kaul, Sanjiv

    2013-01-01

    There is controversy regarding the superiority of carvedilol (C) over metoprolol (M) in congestive heart failure. We hypothesized that C is superior to M in chronic ischemic cardiomyopathy because of its better anti-inflammatory and pro-angiogenic effects. In order to test our hypothesis we used a chronic canine model of multivessel ischemic cardiomyopathy where myocardial microcatheters were placed from which interstitial fluid was collected over time to measure leukocyte count and cytokine levels. After development of left ventricular dysfunction, the animals were randomized into four groups: sham (n = 7), placebo (n = 8), M (n = 11), and C (n = 10), and followed for 3 months after treatment initiation. Tissue was examined for immunohistochemistry, oxidative stress, and capillary density. At 3 months both rest and stress wall thickening were better in C compared to the other groups. At the end of 3 months of treatment endsystolic wall stress also decreased the most in C. Similarly resting myocardial blood flow (MBF) improved the most in C as did the stress endocardial/epicardial MBF. Myocardial interstitial fluid showed greater attenuation of leukocytosis with C compared to M, which was associated with less fibrosis and oxidative stress. C also had higher IL-10 level and capillary density. In conclusion, in a chronic canine model of multivessel ischemic cardiomyopathy we found 3 months of C treatment resulted in better resting global and regional function as well as better regional function at stress compared to M. These changes were associated with higher myocardial levels of the anti-inflammatory cytokine IL-10 and less myocardial oxidative stress, leukocytosis, and fibrosis. Capillary density and MBF were almost normalized. Thus in the doses used in this study, C appears to be superior to M in a chronic canine model of ischemic cardiomyopathy from beneficial effects on inflammation and angiogenesis. Further studies are required for comparing additional doses

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

    PubMed

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

    2016-02-01

    In Stage II colon cancer, multiple independent studies have shown that a dense intratumoural immune infiltrate (local inflammation) is associated with improved outcomes, while systemic inflammation, measured by various markers, has been associated with poorer outcomes. However, previous studies have not considered the interaction between local and systemic inflammation, nor have they assessed the type of inflammatory response compared with standard clinicopathologic criteria. In order to evaluate the potential clinical utility of inflammatory markers in Stage II colon cancer, we examined local and systemic inflammation in a consecutive series of patients with resected Stage II colon cancer between 2000 and 2010 who were identified from a prospective clinical database. Increased intratumoural chronic inflammatory cell (CIC) density, as assessed by pathologist review of hematoxylin and eosin stained slides, was used to represent local inflammation. Neutrophil-to-lymphocyte ratio (NLR) >5, as calculated from pre-operative full blood counts, was used to represent systemic inflammation. In 396 eligible patients identified, there was a non-significant inverse relationship between local and systemic inflammation. Increased CIC density was significantly associated with improved overall (HR 0.45, p = 0.001) and recurrence-free survival (HR 0.37, p = 0.003). High NLR was significantly associated with poorer overall survival (HR 2.56, p < 0.001). The combination of these markers further stratified prognosis independent of standard high-risk criteria, with a dominant systemic inflammatory response (low CIC/high NLR) associated with the worst outcome (5-year overall survival 55.8%). With further validation this simple, inexpensive combined inflammatory biomarker might assist in patient selection for adjuvant chemotherapy in Stage II colon cancer. PMID:26270488

  8. Curcumin, Silybin Phytosome(®) and α-R-Lipoic Acid Mitigate Chronic Hepatitis in Rat by Inhibiting Oxidative Stress and Inflammatory Cytokines Production.

    PubMed

    Ali, Shimaa O; Darwish, Hebatallah A; Ismail, Nabila A

    2016-05-01

    Chronic hepatitis is recognized as a worldwide health problem that gradually progresses towards cirrhosis and hepatocellular carcinoma. Despite the large number of experiments using animal models for allergic hepatitis, it is still difficult to produce a picture of chronic hepatitis. Therefore, this study was conducted to introduce an animal model approximating to the mechanism of chronicity in human hepatitis. The study also aimed to examine the hepatoprotective effects of curcumin, silybin phytosome(®) and α-R-lipoic acid against thioacetamide (TAA)-induced chronic hepatitis in rat model. TAA was administered intraperitoneally at a dose of 200 mg/kg three times weekly for 4 weeks. At the end of this period, a group of rats was killed to assess the development of chronic hepatitis in comparison with their respective control group. TAA administration was then discontinued, and the remaining animals were subsequently allocated into four groups. Group 1 was left untreated, whereas groups 2-4 were allowed to receive daily oral doses of curcumin, silybin phytosome(®) or α-R-lipoic acid, respectively, for 7 weeks. Increases in hepatic levels of malondialdehyde associated with TAA administration were inhibited in groups receiving supplements. Furthermore, glutathione depletion, collagen deposition, macrophage activation and nuclear factor κappa-B expression as well as tumour necrosis factor-α and interleukin-6 levels were significantly decreased in response to supplements administration. Serological analysis of liver function and liver histopathological examination reinforced the results. The above evidence collectively indicates that the antioxidant and anti-inflammatory activities of curcumin, silybin phytosome(®) and α-R-lipoic acid may confer therapeutic efficacy against chronic hepatitis. PMID:26457982

  9. Provenance through Time

    NASA Astrophysics Data System (ADS)

    Chandler, C. L.; Groman, R. C.; Shepherd, A.; Allison, M. D.; Kinkade, D.; Rauch, S.; Wiebe, P. H.; Glover, D. M.

    2014-12-01

    The ability to reproduce scientific results is a cornerstone of the scientific method, and access to the data upon which the results are based is essential to reproducibility. Access to the data alone is not enough though, and research communities have recognized the importance of metadata (data documentation) to enable discovery and data access, and facilitate interpretation and accurate reuse. The Biological and Chemical Oceanography Data Management Office (BCO-DMO) was first funded in late 2006 by the National Science Foundation (NSF) Division of Ocean Sciences (OCE) Biology and Chemistry Sections to help ensure that data generated during NSF OCE funded research would be preserved and available for future use. The BCO-DMO was formed by combining the formerly independent data management offices of two marine research programs: the United States Joint Global Ocean Flux Study (US JGOFS) and the US GLOBal Ocean ECosystems Dynamics (US GLOBEC) program. Since the US JGOFS and US GLOBEC programs were both active (1990s) there have been significant changes in all aspects of the research data life cycle, and the staff at BCO-DMO has modified the way in which we manage data contributed to the office. The supporting documentation that describes each dataset was originally displayed as a human-readable text file retrievable via a Web browser. BCO-DMO still offers that form because our primary audience is marine researchers using Web browser clients; however we are seeing an increased demand to support machine client access. Metadata records from the BCO-DMO data system are now extracted and published out in a variety of formats. The system supports ISO 19115, FGDC, GCMD DIF, schema.org Dataset extension, formal publication with a DOI, and RDF with semantic markup including PROV-O, FOAF and more. In the 1990s, data documentation helped researchers locate data of interest and understand the provenance sufficiently to determine fitness for purpose. Today, providing data

  10. Promotion of a cancer-like phenotype, through chronic exposure to inflammatory cytokines and hypoxia in a bronchial epithelial cell line model

    PubMed Central

    Baird, Anne-Marie; Gray, Steven G.; Richard, Derek J.; O’Byrne, Kenneth J.

    2016-01-01

    Globally, lung cancer accounts for approximately 20% of all cancer related deaths. Five-year survival is poor and rates have remained unchanged for the past four decades. There is an urgent need to identify markers of lung carcinogenesis and new targets for therapy. Given the recent successes of immune modulators in cancer therapy and the improved understanding of immune evasion by tumours, we sought to determine the carcinogenic impact of chronic TNF-α and IL-1β exposure in a normal bronchial epithelial cell line model. Following three months of culture in a chronic inflammatory environment under conditions of normoxia and hypoxia (0.5% oxygen), normal cells developed a number of key genotypic and phenotypic alterations. Important cellular features such as the proliferative, adhesive and invasive capacity of the normal cells were significantly amplified. In addition, gene expression profiles were altered in pathways associated with apoptosis, angiogenesis and invasion. The data generated in this study provides support that TNF-α, IL-1β and hypoxia promotes a neoplastic phenotype in normal bronchial epithelial cells. In turn these mediators may be of benefit for biomarker and/or immune-therapy target studies. This project provides an important inflammatory in vitro model for further immuno-oncology studies in the lung cancer setting. PMID:26759080

  11. Minimally Invasive Surgery for Inflammatory Bowel Disease

    PubMed Central

    Holder-Murray, Jennifer; Marsicovetere, Priscilla

    2015-01-01

    Abstract: Surgical management of inflammatory bowel disease is a challenging endeavor given infectious and inflammatory complications, such as fistula, and abscess, complex often postoperative anatomy, including adhesive disease from previous open operations. Patients with Crohn's disease and ulcerative colitis also bring to the table the burden of their chronic illness with anemia, malnutrition, and immunosuppression, all common and contributing independently as risk factors for increased surgical morbidity in this high-risk population. However, to reduce the physical trauma of surgery, technologic advances and worldwide experience with minimally invasive surgery have allowed laparoscopic management of patients to become standard of care, with significant short- and long-term patient benefits compared with the open approach. In this review, we will describe the current state-of the-art for minimally invasive surgery for inflammatory bowel disease and the caveats inherent with this practice in this complex patient population. Also, we will review the applicability of current and future trends in minimally invasive surgical technique, such as laparoscopic “incisionless,” single-incision laparoscopic surgery (SILS), robotic-assisted, and other techniques for the patient with inflammatory bowel disease. There can be no doubt that minimally invasive surgery has been proven to decrease the short- and long-term burden of surgery of these chronic illnesses and represents high-value care for both patient and society. PMID:25989341

  12. Roles of MAS-related G protein coupled receptor-X2 (MRGPRX2) on mast cell-mediated host defense, pseudoallergic drug reactions and chronic inflammatory diseases

    PubMed Central

    Subramanian, Hariharan; Gupta, Kshitij; Ali, Hydar

    2016-01-01

    Mast cells (MCs), which are granulated tissue-resident cells of hematopoietic lineage, contribute to vascular homeostasis, innate/adaptive immunity and wound healing. MCs are, however, best known for their roles in allergic and inflammatory diseases such as anaphylaxis, food allergy, rhinitis, itch, urticaria, atopic dermatitis and asthma. In addition to the high affinity IgE receptor (FcεRI), MCs express numerous G protein coupled receptors (GPCRs), which are the largest group of membrane receptor proteins and are the most common targets of drug therapy. Antimicrobial host defense peptides (HDPs), neuropeptides (NPs), major basic protein (MBP), eosinophil peroxidase (EPO) and many FDA approved peptidergic drugs activate human MCs via a novel GPCR known as MAS-related G protein coupled receptor-X2 (MRGPRX2; formerly known as MrgX2). Unique features of MRGPRX2 that distinguish it from other GPCRs include their presence both on plasma membrane and intracellular sites and their selective expression in MCs. In this article, we review the possible roles of MRGPRX2 on host defense, drug-induced anaphylactoid reactions, neurogenic inflammation, pain, itch and chronic inflammatory diseases such as urticaria and asthma. We propose that HDPs that kill microbes directly and activate MCs via MRGPRX2 could serve as novel GPCR targets to modulate host defense against microbial infection. Furthermore, monoclonal antibodies or small molecule inhibitors of MRGPRX2 could be developed for the treatment of MC-dependent allergic and inflammatory disorders. PMID:27448446

  13. Elevated Plasma Level of Interferon-λ1 in Chronic Spontaneous Urticaria: Upregulated Expression in CD8+ and Epithelial Cells and Induction of Inflammatory Cell Accumulation

    PubMed Central

    Wang, S. F.; Gao, X. Q.; Xu, Y. N.; Li, D. N.; Wang, H. Y.

    2016-01-01

    Interferon- (IFN-) λ1 is regarded as a potent bio-active molecule in innate immunity. However, little is known about its role in chronic spontaneous urticaria (CSU). We therefore investigated expression of IFN-λ1 in CSU, its cellular location, and its influence on inflammatory cell accumulation by using flow cytometry analysis, skin tissue dispersion, immunohistochemical stain, and a mouse peritoneal inflammation model. The results showed that level of IFN-λ1 was 2.0-fold higher in plasma of the patients with CSU than the level in healthy control (HC) subjects. Among leukocytes examined, only CD8+ T cells expressed more IFN-λ1 in CSU blood. Double labeling immunohistochemical staining revealed that IFN-λ1+ inflammatory cells such as mast cells, eosinophils, B cells, neutrophils, and macrophages were mainly located in dermis, whereas epidermis tissue highly expressed IFN-λ1. IFN-λ1 induced a dose-dependent increase in number of eosinophils, lymphocytes, mast cells, macrophages, and neutrophils in the peritoneum of mice at 6 h following injection, which was inhibited by pretreatment of the animals with anti-intercellular adhesion molecule- (ICAM-) 1 and/or anti-L-selectin antibodies. In conclusion, IFN-λ1 is likely to play a role in the pathogenesis of CSU. Blocking IFN-λ1 production may help to reduce the accumulation of inflammatory cells in the involved CSU skin. PMID:27445435

  14. [Inflammatory Bowel Disease Competence Network].

    PubMed

    Schreiber, Stefan; Hartmann, Heinz; Kruis, Wolfgang; Kucharzik, Torsten; Mudter, Jonas; Siegmund, Britta; Stallmach, Andreas; Witte, Christine; Fitzke, Klaus; Bokemeyer, Bernd

    2016-04-01

    The Inflammatory Bowel Disease Competence Network is a network of more than 500 physicians and scientists from university clinics, hospitals and gastroenterology practices. The focus extends from the two major forms of inflammatory bowel diseases, Crohn's disease and ulcerative colitis, into other chronic inflammatory conditions affecting the intestine, including coeliac disease and microscopic colitis. The network translates basic science discoveries (in particular in the molecular epidemiology research) into innovative diagnostics and therapy. Through its strong networking structures it supports a continuous process to improve quality and standardisation in patient care that is implemented in close interaction with European networks addressing this disease group.Optimisation of patient care based on scientifically proven evidence is a main focus of the network. Therefore, it supports and coordinates translational research and infrastructure projects that investigate aetiology, improvement of diagnostic methods, and development of new or improved use of established therapies. Members participate in various training projects, thus ensuring the rapid transfer of research results into clinical practice.The competence network cooperates with the main patient organisations to engage patients in all levels of activities. The network and the patient organisations have interest in promoting public awareness about the disease entities, because their importance and burden is underestimated in non-specialised medical fields and among the general public. PMID:26968556

  15. Neutrophil elastase (NE) and NE inhibitors: canonical and noncanonical functions in lung chronic inflammatory diseases (cystic fibrosis and chronic obstructive pulmonary disease).

    PubMed

    Roghanian, Ali; Sallenave, Jean-Michel

    2008-03-01

    Proteases and antiproteases have multiple important roles both in normal homeostasis and during inflammation. Antiprotease molecules may have developed in a parallel network, consisting of "alarm" and "systemic" inhibitors. Their primary function was thought until recently to mainly prevent the potential injurious effects of excess release of proteolytic enzymes, such as neutrophil elastase (NE), from inflammatory cells. However, recently, new potential roles have been ascribed to these antiproteases. We will review "canonical" and new "noncanonical" functions for these molecules, and more particularly, those pertaining to their role in innate and adaptive immunity (antibacterial activity and biasing of the adaptive immune response). PMID:18518838

  16. Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci.

    PubMed

    Ellinghaus, David; Jostins, Luke; Spain, Sarah L; Cortes, Adrian; Bethune, Jörn; Han, Buhm; Park, Yu Rang; Raychaudhuri, Soumya; Pouget, Jennie G; Hübenthal, Matthias; Folseraas, Trine; Wang, Yunpeng; Esko, Tonu; Metspalu, Andres; Westra, Harm-Jan; Franke, Lude; Pers, Tune H; Weersma, Rinse K; Collij, Valerie; D'Amato, Mauro; Halfvarson, Jonas; Jensen, Anders Boeck; Lieb, Wolfgang; Degenhardt, Franziska; Forstner, Andreas J; Hofmann, Andrea; Schreiber, Stefan; Mrowietz, Ulrich; Juran, Brian D; Lazaridis, Konstantinos N; Brunak, Søren; Dale, Anders M; Trembath, Richard C; Weidinger, Stephan; Weichenthal, Michael; Ellinghaus, Eva; Elder, James T; Barker, Jonathan N W N; Andreassen, Ole A; McGovern, Dermot P; Karlsen, Tom H; Barrett, Jeffrey C; Parkes, Miles; Brown, Matthew A; Franke, Andre

    2016-05-01

    We simultaneously investigated the genetic landscape of ankylosing spondylitis, Crohn's disease, psoriasis, primary sclerosing cholangitis and ulcerative colitis to investigate pleiotropy and the relationship between these clinically related diseases. Using high-density genotype data from more than 86,000 individuals of European ancestry, we identified 244 independent multidisease signals, including 27 new genome-wide significant susceptibility loci and 3 unreported shared risk loci. Complex pleiotropy was supported when contrasting multidisease signals with expression data sets from human, rat and mouse together with epigenetic and expressed enhancer profiles. The comorbidities among the five immune diseases were best explained by biological pleiotropy rather than heterogeneity (a subgroup of cases genetically identical to those with another disease, possibly owing to diagnostic misclassification, molecular subtypes or excessive comorbidity). In particular, the strong comorbidity between primary sclerosing cholangitis and inflammatory bowel disease is likely the result of a unique disease, which is genetically distinct from classical inflammatory bowel disease phenotypes. PMID:26974007

  17. Neurotropin attenuates local inflammatory response and inhibits demyelination induced by chronic constriction injury of the mouse sciatic nerve.

    PubMed

    Nishimoto, Shunsuke; Okada, Kiyoshi; Tanaka, Hiroyuki; Okamoto, Michio; Fujisawa, Hiroki; Okada, Tomoyuki; Naiki, Mitsuru; Murase, Tsuyoshi; Yoshikawa, Hideki

    2016-07-01

    Neuropathic pain caused by nerve damage in the central and/or peripheral nervous systems is a refractory disorder and the management of such chronic pain has become a major issue. Neurotropin is a drug widely used in Japan and China to treat chronic pain. Although Neurotropin has been demonstrated to suppress chronic pain through the descending pain inhibitory system, the mechanism of analgesic action in the peripheral nervous system remains to be elucidated. In this study, we investigated the local effects of Neurotropin on peripheral nerve damage in a chronic constriction injury (CCI) model. Neurotropin reduced mRNA expressions of IL-1β, IL-6, and TNF-α in the sciatic nerve 1 day after the injury. Activation of Erk was also inhibited locally in the Neurotropin treatment group. Since Erk activation results in demyelination along with dedifferentiation of Schwann cells, we investigated the expression level of myelin basic protein. Five days after the injury, Neurotropin attenuated the downregulation of myelin basic protein in the sciatic nerve in the CCI model. Local effects of Neurotropin around the injury site may result in discovery of new treatments for not only neuropathic pain but also demyelinating diseases and peripheral nervous system injury. PMID:27233579

  18. Non-invasive, photonics-based diagnostic, imaging, monitoring, and light delivery techniques for the recognition, quantification and treatment of malignant and chronic inflammatory conditions

    NASA Astrophysics Data System (ADS)

    Davies, N.; Davies-Shaw, D.; Shaw, J. D.

    2007-02-01

    We report firsthand on innovative developments in non-invasive, biophotonic techniques for a wide range of diagnostic, imaging and treatment options, including the recognition and quantification of cancerous, pre-cancerous cells and chronic inflammatory conditions. These techniques have benefited from the ability to target the affected site by both monochromatic light and broad multiple wavelength spectra. The employment of such wavelength or color-specific properties embraces the fluorescence stimulation of various photosensitizing drugs, and the instigation and detection of identified fluorescence signatures attendant upon laser induced fluorescence (LIF) phenomena as transmitted and propagated by precancerous, cancerous and normal tissue. In terms of tumor imaging and therapeutic and treatment options, we have exploited the abilities of various wavelengths to penetrate to different depths, through different types of tissues, and have explored quantifiable absorption and reflection characteristics upon which diagnostic assumptions can be reliably based and formulated. These biophotonic-based diagnostic, sensing and imaging techniques have also benefited from, and have been further enhanced by, the integrated ability to provide various power levels to be employed at various stages in the procedure. Applications are myriad, including non-invasive, non destructive diagnosis of in vivo cell characteristics and functions; light-based tissue analysis; real-time monitoring and mapping of brain function and of tumor growth; real time monitoring of the surgical completeness of tumor removal during laser-imaged/guided brain resection; diagnostic procedures based on fluorescence life-time monitoring, the monitoring of chronic inflammatory conditions (including rheumatoid arthritis), and continuous blood glucose monitoring in the control of diabetes.

  19. Provenance of unknown plutonium material.

    PubMed

    Nicolaou, G

    2008-10-01

    The determination of the provenance of 'unknown' plutonium material is demonstrated through a simulation study based on an isotopic fingerprinting approach. Plutonium of known provenance was considered as the 'unknown' nuclear material in order to evaluate the potential of the approach and verify its predictive capabilities. Factor analysis was used to compare the Pu isotopic composition of the 'unknown' material with Pu isotopic compositions simulating well known spent fuels from a range of commercial nuclear power stations. The provenance of the 'unknown material' is assigned to the commercial fuel with which exhibits the highest degree of similarity with respect to the Pu composition. The approach appears promising since it accurately predicted the provenance of the one 'unknown' sample considered; nevertheless, the approach is still at the development stage. Important challenging issues related to the simulation uncertainties and its testing on real laboratory samples have to be explored prior to evaluating the potential of the approach. PMID:18639370

  20. Identifying viral infections in vaccinated Chronic Obstructive Pulmonary Disease (COPD) patients using clinical features and inflammatory markers

    PubMed Central

    Hutchinson, Anastasia F.; Black, Jim; Thompson, Michelle A.; Bozinovski, Steven; Brand, Caroline A.; Smallwood, David M.; Irving, Louis B.; Anderson, Gary P.

    2009-01-01

    Background  Known inflammatory markers have limited sensitivity and specificity to differentiate viral respiratory tract infections from other causes of acute exacerbation of COPD (AECOPD). To overcome this, we developed a multi‐factorial prediction model combining viral symptoms with inflammatory markers. Methods  Interleukin‐6 (IL‐6), serum amyloid A (SAA) and viral symptoms were measured in stable COPD and at AECOPD onset and compared with the viral detection rates on multiplex PCR. The predictive accuracy of each measure was assessed using logistic regression and receiver operating characteristics curve (ROC) analysis. Results  There was a total of 33 viruses detected at the onset of 148 AECOPD, the majority 26 (79%) were picornavirus. Viral symptoms with the highest predictive values were rhinorrhoea [Odds ratio (OR) 4·52; 95% CI 1·99–10·29; P < 0·001] and sore throat (OR 2·64; 95% CI 1·14–6·08; P = 0·022), combined the AUC ROC curve was 0·67. At AECOPD onset patients experienced a 1·6‐fold increase in IL‐6 (P = 0·008) and 4·5‐fold increase in SAA (P < 0·001). The addition of IL‐6 to the above model significantly improved diagnostic accuracy compared with symptoms alone (AUC ROC 0·80 (P = 0·012). Conclusion  The addition of inflammatory markers increases the specificity of a clinical case definition for viral infection, particularly picornavirus infection. PMID:20021505

  1. The effects of grounding (earthing) on inflammation, the immune response, wound healing, and prevention and treatment of chronic inflammatory and autoimmune diseases

    PubMed Central

    Oschman, James L; Chevalier, Gaétan; Brown, Richard

    2015-01-01

    Multi-disciplinary research has revealed that electrically conductive contact of the human body with the surface of the Earth (grounding or earthing) produces intriguing effects on physiology and health. Such effects relate to inflammation, immune responses, wound healing, and prevention and treatment of chronic inflammatory and autoimmune diseases. The purpose of this report is two-fold: to 1) inform researchers about what appears to be a new perspective to the study of inflammation, and 2) alert researchers that the length of time and degree (resistance to ground) of grounding of experimental animals is an important but usually overlooked factor that can influence outcomes of studies of inflammation, wound healing, and tumorigenesis. Specifically, grounding an organism produces measurable differences in the concentrations of white blood cells, cytokines, and other molecules involved in the inflammatory response. We present several hypotheses to explain observed effects, based on current research results and our understanding of the electronic aspects of cell and tissue physiology, cell biology, biophysics, and biochemistry. An experimental injury to muscles, known as delayed onset muscle soreness, has been used to monitor the immune response under grounded versus ungrounded conditions. Grounding reduces pain and alters the numbers of circulating neutrophils and lymphocytes, and also affects various circulating chemical factors related to inflammation. PMID:25848315

  2. Inclusion of Cocoa as a Dietary Supplement Represses Expression of Inflammatory Proteins in Spinal Trigeminal Nucleus in Response to Chronic Trigeminal Nerve Stimulation

    PubMed Central

    Cady, Ryan J.; Denson, Jennifer E.; Durham, Paul L.

    2013-01-01

    Scope Central sensitization is implicated in the pathology of temporomandibular joint disorder (TMD) and other types of orofacial pain. We investigated the effects of dietary cocoa on expression of proteins involved in the development of central sensitization in the spinal trigeminal nucleus (STN) in response to inflammatory stimulation of trigeminal nerves. Methods and results Male Sprague Dawley rats were fed either a control diet or an isocaloric diet consisting of 10% cocoa powder 14 days prior to bilateral injection of complete Freund’s adjuvant (CFA) into the temporomandibular joint to promote prolonged activation of trigeminal ganglion neurons and glia. While dietary cocoa stimulated basal expression of GLAST and MKP-1 when compared to animals on a normal diet, cocoa suppressed basal calcitonin gene-related peptide levels in the STN. CFA-stimulated levels of protein kinase A, P2X3, P-p38, GFAP, and OX-42, whose elevated levels in the STN are implicated in central sensitization, were repressed to near control levels in animals on a cocoa enriched diet. Similarly, dietary cocoa repressed CFA-stimulated inflammatory cytokine expression. Conclusion Based on our findings, we speculate that cocoa enriched diets could be beneficial as a natural therapeutic option for TMD and other chronic orofacial pain conditions. PMID:23576361

  3. Effects of “Danzhi Decoction” on Chronic Pelvic Pain, Hemodynamics, and Proinflammatory Factors in the Murine Model of Sequelae of Pelvic Inflammatory Disease

    PubMed Central

    Bu, Xiaoling; Liu, Yanxia; Lu, Qiudan; Jin, Zhe

    2015-01-01

    Objective. To evaluate the effect of Danzhi decoction (DZD) on chronic pelvic pain (CPP), hemodynamics, and proinflammatory factors of sequelae of pelvic inflammatory diseases (SPID) in murine model. Methods. SPID mice were randomly treated with high-dose DZD, mid-dose DZD, low-dose DZD, aspirin, and vehicle for 3 estrous circles. The Mouse Grimace Scale (MGS) was performed to evaluate CPP; blood flows of the upper genital tract, pelvic wall, and mesentery were used to assess hemodynamics in SPID mice; expressions of vascular endothelial growth factor (VEGF), angiopoietin-2 (Ang-2), and osteopontin (OPN) were measured by Western blot and immunochemistry. Results. Treatment with dose-dependent DZD significantly decreased the MGS scores, accelerated blood flows of the pelvis, and reduced expressions of VEGF, Ang-2, and OPN in the upper genital tract. Conclusions and Discussions. DZD was effective in relieving CPP and improving hemodynamics of the pelvic blood-stasis microenvironment in SPID mice. There was a relationship between CPP and the pelvic blood-stasis microenvironment. Furthermore, DZD might play a positive role in the anti-inflammatory process. PMID:27087818

  4. Phosphocholine‐containing ligands direct CRP induction of M2 macrophage polarization independent of T cell polarization: Implication for chronic inflammatory states

    PubMed Central

    Cieslik, Katarzyna A.; Entman, Mark L.

    2016-01-01

    Introduction We studied monocyte transendothelial migration and subsequent polarization into M1/M2 macrophages in response to C‐reactive protein (CRP) with two disease‐related ligands: (1) phosphocholine (PC) and (2) multilamellar liposomes containing both unoxidized and oxidized forms of the lipid, phosphatidylcholine. These ligands differ in biological origin: PC is present on bacterial cell walls while oxidized lipids are present in atherogenic lipids. Methods We used an in vitro model of human monocyte transendothelial migration and assessed the polarization of monocytes and T cells and signaling through Fcγ receptors in monocytes. Results CRP without ligands did not promote M2 macrophage differentiation over background levels. However, when paired with either ligand, it increased M2 numbers. M2 differentiation was dependent on IL‐13, and in the case of CRP with PC, was associated with a Th2 response. Paradoxically, while CRP with PC initiated a Th2 response, the combination of liposomes with CRP resulted in a Th1 response without any change in Th2 numbers despite association with M2 macrophage polarization. To resolve the conundrum of an anti‐inflammatory macrophage response coexisting with a proinflammatory T cell response, we investigated signaling of CRP and its ligands through Fcγ receptors, which leads to macrophage activation independent of T cell signaling. We found that CRP plus PC acted via FcγRI, whereas CRP with liposomes bound to FcγRII. Both were activating signals as evidenced by SYK phosphorylation. Conclusion We conclude that CRP with ligands can promote M2 macrophage differentiation to fibroblasts through FcγR activation, and this may result in an anti‐inflammatory influence despite a proinflammatory T cell environment caused by oxidized lipids. The potential relationship of this mechanism to chronic inflammatory disease is discussed. PMID:27621811

  5. Thymoquinone ameliorated elevated inflammatory cytokines in testicular tissue and sex hormones imbalance induced by oral chronic toxicity with sodium nitrite.

    PubMed

    Alyoussef, Abdullah; Al-Gayyar, Mohammed M H

    2016-07-01

    Scientific evidence illustrated the health hazards of exposure to nitrites for prolonged time. Nitrites affected several body organs due to oxidative, inflammatory and apoptosis properties. Furthermore, thymoquinone (TQ) had curative effects against many diseases. We tried to discover the impact of both sodium nitrite and TQ on inflammatory cytokines contents in testicular tissues and hormonal balance both in vivo and in vitro. Fifty adult male SD rats received 80mg/kg sodium nitrite and treated with either 25 or 50mg/kg TQ daily by oral-gavage for twelve weeks. Testis were removed for sperms' count. Testicular tissue homogenates were used for assessment of protein and gene expression of IL-1β, IL-6, TNF-α, Nrf2 and caspase-3. Serum samples were used for measurement of testosterone, LH, FSH and prolactin. Moreover, all the parameters were measured in human normal testis cell-lines, CRL-7002. Sodium nitrite produced significant decrease in serum testosterone associated with raised FSH, LH and prolactin. Moreover, sodium nitrite significantly elevated TNF-α, IL-1β, IL-6, caspase-3 and reduced Nrf2. TQ significantly reversed all these effects both in vivo and in vitro. In conclusion, TQ ameliorated testicular tissue inflammation and restored the normal balance of sex hormones induced by sodium nitrite both in vivo and in vitro. PMID:27038016

  6. Androgen-androgen receptor system improves chronic inflammatory conditions by suppressing monocyte chemoattractant protein-1 gene expression in adipocytes via transcriptional regulation.

    PubMed

    Morooka, Nobukatsu; Ueguri, Kei; Yee, Karen Kar Lye; Yanase, Toshihiko; Sato, Takashi

    2016-09-01

    Age-related decreases in sex hormones are closely related to chronic inflammation in obesity and metabolic diseases. Particularly, the molecular basis of androgen activity in regulating inflammation and controlling metabolism remains largely unknown. Obese adipocytes secrete monocyte chemoattractant protein-1 (MCP-1), a key chemokine that promotes the infiltration of monocytes/macrophages into adipose tissue, thereby leading to metabolic disorders. Here, we studied the role of androgen-androgen receptor (AR) action in regulating MCP-1 expression in adipose tissue. We observed the induction of Mcp-1 expression in 3T3-L1 adipocytes co-cultured with RAW264.7 macrophages. Additionally, Mcp-1 expression was upregulated by culturing in conditioned medium derived from inflammatory macrophages (M1-Mφ) containing tumor necrosis factor-alpha (TNF-α). We found that sex hormones downregulated TNF-α-induced Mcp-1 and interleukin (Il)-6 expression in 3T3-L1 adipocytes. Furthermore, luciferase-reporter analysis indicated that MCP-1 promoter activity was predominantly suppressed by dihydrotestosterone (DHT)-AR interactions through functional canonical nuclear factor-kappa B (NF-κB) sites, whereas non-canonical NF-κB site containing important flanking sequences exhibited minor contributions to DHT-AR transcriptional repression. These findings suggested that androgen-AR suppressed obesity-induced chronic inflammation in adipose tissue. PMID:27392713

  7. Chronic Administration of Δ9-Tetrahydrocannabinol Induces Intestinal Anti-Inflammatory MicroRNA Expression during Acute Simian Immunodeficiency Virus Infection of Rhesus Macaques

    PubMed Central

    Chandra, Lawrance C.; Kumar, Vinay; Torben, Workineh; Stouwe, Curtis Vande; Winsauer, Peter; Amedee, Angela; Molina, Patricia E.

    2014-01-01

    ABSTRACT Recreational and medical use of cannabis among human immunodeficiency virus (HIV)-infected individuals has increased in recent years. In simian immunodeficiency virus (SIV)-infected macaques, chronic administration of Δ9-tetrahydrocannabinol (Δ9-THC) inhibited viral replication and intestinal inflammation and slowed disease progression. Persistent gastrointestinal disease/inflammation has been proposed to facilitate microbial translocation and systemic immune activation and promote disease progression. Cannabinoids including Δ9-THC attenuated intestinal inflammation in mouse colitis models and SIV-infected rhesus macaques. To determine if the anti-inflammatory effects of Δ9-THC involved differential microRNA (miRNA) modulation, we profiled miRNA expression at 14, 30, and 60 days postinfection (days p.i.) in the intestine of uninfected macaques receiving Δ9-THC (n = 3) and SIV-infected macaques administered either vehicle (VEH/SIV; n = 4) or THC (THC/SIV; n = 4). Chronic Δ9-THC administration to uninfected macaques significantly and positively modulated intestinal miRNA expression by increasing the total number of differentially expressed miRNAs from 14 to 60 days p.i. At 60 days p.i., ∼28% of miRNAs showed decreased expression in the VEH/SIV group compared to none showing decrease in the THC/SIV group. Furthermore, compared to the VEH/SIV group, THC selectively upregulated the expression of miR-10a, miR-24, miR-99b, miR-145, miR-149, and miR-187, previously been shown to target proinflammatory molecules. NOX4, a potent reactive oxygen species generator, was confirmed as a direct miR-99b target. A significant increase in NOX4+ crypt epithelial cells was detected in VEH/SIV macaques compared to the THC/SIV group. We speculate that miR-99b-mediated NOX4 downregulation may protect the intestinal epithelium from oxidative stress-induced damage. These results support a role for differential miRNA induction in THC-mediated suppression of intestinal

  8. Carboxylated, heteroaryl-substituted chalcones as inhibitors of vascular cell adhesion molecule-1 expression for use in chronic inflammatory diseases.

    PubMed

    Meng, Charles Q; Ni, Liming; Worsencroft, Kimberly J; Ye, Zhihong; Weingarten, M David; Simpson, Jacob E; Skudlarek, Jason W; Marino, Elaine M; Suen, Ki-Ling; Kunsch, Charles; Souder, Amy; Howard, Randy B; Sundell, Cynthia L; Wasserman, Martin A; Sikorski, James A

    2007-03-22

    Starting from a simple chalcone template, structure-activity relationship (SAR) studies led to a series of carboxylated, heteroaryl-substituted chalcone derivatives as novel, potent inhibitors of vascular cell adhesion molecule-1 (VCAM-1) expression. Correlations between lipophilicity determined by calculated logP values and inhibitory efficacy were observed among structurally similar compounds of the series. Various substituents were found to be tolerated at several positions of the chalcone backbone as long as the compounds fell into the right range of lipophilicity. The chalcone alpha,beta-unsaturated ketone moiety seemed to be the pharmacophore required for inhibition of VCAM-1 expression. Compound 19 showed significant antiinflammatory effects in a mouse model of allergic inflammation, indicating that this series of compounds might have therapeutic value for human asthma and other inflammatory disorders. PMID:17323940

  9. Inflammatory glaucoma

    PubMed Central

    Bodh, Sonam A.; Kumar, Vasu; Raina, Usha K.; Ghosh, B.; Thakar, Meenakshi

    2011-01-01

    Glaucoma is seen in about 20% of the patients with uveitis. Anterior uveitis may be acute, subacute, or chronic. The mechanisms by which iridocyclitis leads to obstruction of aqueous outflow include acute, usually reversible forms (e.g., accumulation of inflammatory elements in the intertrabecular spaces, edema of the trabecular lamellae, or angle closure due to ciliary body swelling) and chronic forms (e.g., scar formation or membrane overgrowth in the anterior chamber angle). Careful history and follow-up helps distinguish steroid-induced glaucoma from uveitic glaucoma. Treatment of combined iridocyclitis and glaucoma involves steroidal and nonsteroidal antiinflammatory agents and antiglaucoma drugs. However, glaucoma drugs can often have an unpredictable effect on intraocular pressure (IOP) in the setting of uveitis. Surgical intervention is required in case of medical failure. Method of Literature Search: Literature on the Medline database was searched using the PubMed interface. PMID:21713239

  10. A Noisy 10GB Provenance Database

    SciTech Connect

    Cheah, You-Wei; Plale, Beth; Kendall-Morwick, Joey; Leake, David; Ramakrishnan, Lavanya

    2011-06-06

    Provenance of scientific data is a key piece of the metadata record for the data's ongoing discovery and reuse. Provenance collection systems capture provenance on the fly, however, the protocol between application and provenance tool may not be reliable. Consequently, the provenance record can be partial, partitioned, and simply inaccurate. We use a workflow emulator that models faults to construct a large 10GB database of provenance that we know is noisy (that is, has errors). We discuss the process of generating the provenance database, and show early results on the kinds of provenance analysis enabled by the large provenance.

  11. Statin Effects on Exacerbation Rates, Mortality, and Inflammatory Markers in Patients with Chronic Obstructive Pulmonary Disease: A Review of Prospective Studies.

    PubMed

    Howard, Meredith L; Vincent, Ashley H

    2016-05-01

    Chronic obstructive pulmonary disease (COPD) is a debilitating, irreversible disease with currently available therapies targeting symptom control and exacerbation reduction. A need for alternative disease-modifying therapies remains, specifically those that may have antiinflammatory and immunomodulatory properties that impact the pathophysiologic components of COPD. Statin drugs, the current gold standard for the treatment of dyslipidemia and prevention of cardiovascular disease (CVD), contain properties that affect the inflammatory disease processes seen in COPD. Several retrospective studies have demonstrated that statins may have a benefit in the reduction of morbidity and mortality in patients with COPD. This has led to prospective trials evaluating the impact of statins on various COPD-related outcomes. This article reviews the current body of prospective evidence for use of statins in patients with COPD. A search of the PubMed/Medline database of English-language articles was conducted from 1964 through November 2015; references of relevant articles were also reviewed for qualifying studies. Prospective studies of all types relating to statin use in patients with COPD were included if they had COPD- or respiratory-related outcomes; ultimately, eight studies were identified for this review. Statin effects on exacerbation rates, mortality, and inflammatory markers in patients with COPD are discussed. Strong prospective evidence does not currently exist to suggest that statins provide a clinical benefit in patients with COPD who do not have other CVD risk factors. Benefits from statins that have been illustrated are likely explained by their impact on underlying CVD risk factors rather than the COPD disease process. An opportunity exists for unanswered questions to be addressed in future studies. PMID:26990316

  12. Species-specific inflammatory responses as a primary component for the development of glomerular lesions in mice and monkeys following chronic administration of a second-generation antisense oligonucleotide.

    PubMed

    Frazier, Kendall S; Sobry, Cécile; Derr, Victoria; Adams, Mike J; Besten, Cathaline Den; De Kimpe, Sjef; Francis, Ian; Gales, Tracy L; Haworth, Richard; Maguire, Shaun R; Mirabile, Rosanna C; Mullins, David; Palate, Bernard; Doorten, Yolanda Ponstein-Simarro; Ridings, James E; Scicchitano, Marshall S; Silvano, Jérémy; Woodfine, Jennie

    2014-07-01

    Chronic administration of drisapersen, a 2'-OMe phosphorothioate antisense oligonucleotide (AON) to mice and monkeys resulted in renal tubular accumulation, with secondary tubular degeneration. Glomerulopathy occurred in both species with species-specific characteristics. Glomerular lesions in mice were characterized by progressive hyaline matrix accumulation, accompanied by the presence of renal amyloid and with subsequent papillary necrosis. Early changes involved glomerular endothelial hypertrophy and degeneration, but the chronic glomerular amyloid and hyaline alterations in mice appeared to be species specific. An immune-mediated mechanism for the glomerular lesions in mice was supported by early inflammatory changes including increased expression of inflammatory cytokines and other immunomodulatory genes within the renal cortex, increased stimulation of CD68 protein, and systemic elevation of monocyte chemotactic protein 1. In contrast, kidneys from monkeys given drisapersen chronically showed less severe glomerular changes characterized by increased mesangial and inflammatory cells, endothelial cell hypertrophy, and subepithelial and membranous electron-dense deposits, with ultrastructural and immunohistochemical characteristics of complement and complement-related fragments. Lesions in monkeys resembled typical features of C3 glomerulopathy, a condition described in man and experimental animals to be linked to dysregulation of the alternative complement pathway. Thus, inflammatory/immune mechanisms appear critical to glomerular injury with species-specific sensitivities for mouse and monkey. The lower observed proinflammatory activity in humans as compared to mice and monkeys may reflect a lower risk of glomerular injury in patients receiving AON therapy. PMID:24292388

  13. Myxomavirus Anti-Inflammatory Chemokine Binding Protein Reduces the Increased Plaque Growth Induced by Chronic Porphyromonas gingivalis Oral Infection after Balloon Angioplasty Aortic Injury in Mice

    PubMed Central

    Lucas, Alexandra R.; Verma, Raj K.; Dai, Erbin; Liu, Liying; Chen, Hao; Kesavalu, Sheela; Rivera, Mercedes; Velsko, Irina; Ambadapadi, Sriram; Chukkapalli, Sasanka; Kesavalu, Lakshmyya

    2014-01-01

    Thrombotic occlusion of inflammatory plaque in coronary arteries causes myocardial infarction. Treatment with emergent balloon angioplasty (BA) and stent implant improves survival, but restenosis (regrowth) can occur. Periodontal bacteremia is closely associated with inflammation and native arterial atherosclerosis, with potential to increase restenosis. Two virus-derived anti-inflammatory proteins, M-T7 and Serp-1, reduce inflammation and plaque growth after BA and transplant in animal models through separate pathways. M-T7 is a broad spectrum C, CC and CXC chemokine-binding protein. Serp-1 is a serine protease inhibitor (serpin) inhibiting thrombotic and thrombolytic pathways. Serp-1 also reduces arterial inflammation and improves survival in a mouse herpes virus (MHV68) model of lethal vasculitis. In addition, Serp-1 demonstrated safety and efficacy in patients with unstable coronary disease and stent implant, reducing markers of myocardial damage. We investigate here the effects of Porphyromonas gingivalis, a periodontal pathogen, on restenosis after BA and the effects of blocking chemokine and protease pathways with M-T7 and Serp-1. ApoE−/− mice had aortic BA and oral P. gingivalis infection. Arterial plaque growth was examined at 24 weeks with and without anti-inflammatory protein treatment. Dental plaques from mice infected with P. gingivalis tested positive for infection. Neither Serp-1 nor M-T7 treatment reduced infection, but IgG antibody levels in mice treated with Serp-1 and M-T7 were reduced. P. gingivalis significantly increased monocyte invasion and arterial plaque growth after BA (P<0.025). Monocyte invasion and plaque growth were blocked by M-T7 treatment (P<0.023), whereas Serp-1 produced only a trend toward reductions. Both proteins modified expression of TLR4 and MyD88. In conclusion, aortic plaque growth in ApoE−/− mice increased after angioplasty in mice with chronic oral P. gingivalis infection. Blockade of chemokines, but not serine

  14. Serum cytokine profiling and enrichment analysis reveal the involvement of immunological and inflammatory pathways in stable patients with chronic obstructive pulmonary disease

    PubMed Central

    Bade, Geetanjali; Khan, Meraj Alam; Srivastava, Akhilesh Kumar; Khare, Parul; Solaiappan, Krishna Kumar; Guleria, Randeep; Palaniyar, Nades; Talwar, Anjana

    2014-01-01

    Chronic obstructive pulmonary disease (COPD) is a major global health problem. It results from chronic inflammation and causes irreversible airway damage. Levels of different serum cytokines could be surrogate biomarkers for inflammation and lung function in COPD. We aimed to determine the serum levels of different biomarkers in COPD patients, the association between cytokine levels and various prognostic parameters, and the key pathways/networks involved in stable COPD. In this study, serum levels of 48 cytokines were examined by multiplex assays in 30 subjects (control, n=9; COPD, n=21). Relationships between serum biomarkers and forced expiratory volume in 1 second, peak oxygen uptake, body mass index, dyspnea score, and smoking were assessed. Enrichment pathways and network analyses were implemented, using a list of cytokines showing differential expression between healthy controls and patients with COPD by Cytoscape and GeneGo Metacore™ software (Thomson-Reuters Corporation, New York, NY, USA). Concentrations of cutaneous T-cell attracting chemokine, eotaxin, hepatocyte growth factor, interleukin 6 (IL-6), IL-16, and stem cell factor are significantly higher in COPD patients compared with in control patients. Notably, this study identifies stem cell factor as a biomarker for COPD. Multiple regression analysis predicts that cutaneous T-cell-attracting chemokine, eotaxin, IL-6, and stem cell factor are inversely associated with forced expiratory volume in 1 second and peak oxygen uptake change, whereas smoking is related to eotaxin and hepatocyte growth factor changes. Enrichment pathways and network analyses reveal the potential involvement of specific inflammatory and immune process pathways in COPD. Identified network interaction and regulation of different cytokines would pave the way for deeper insight into mechanisms of the disease process. PMID:25125975

  15. Increased Risk of End-Stage Renal Disease (ESRD) Requiring Chronic Dialysis is Associated With Use of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

    PubMed Central

    Chang, Yu-Kang; Liu, Jia-Sin; Hsu, Yueh-Han; Tarng, Der-Cherng; Hsu, Chih-Cheng

    2015-01-01

    Abstract It is known that many medical adverse events can be caused by nonsteroidal anti-inflammatory drugs (NSAIDs); however, epidemiologic evidence has not granted an affirmative relationship between NSAID use and the risk of end-stage renal disease (ESRD). We aimed to investigate the relationship in a Chinese population between short-term NSAID use and development of ESRD requiring chronic dialysis. A retrospective case-crossover design was used in this study. Using the Taiwanese National Health Insurance database, we identified 109,400 incident chronic ESRD patients with dialysis initiation from 1998 to 2009. For each patient, we defined the case period as 1 to 14 days and the control period as 105 to 118 days, respectively, before the first dialysis date. The washout period was 90 days between the case and control period. Detailed information about NSAID use was compared between the case and control periods. We calculated odds ratios (ORs) and their 95% confidence intervals (CIs) using a conditional logistic regression model. NSAID use was found to be a significant risk factor associated with dialysis commencement. The adjusted OR was 2.73 (95% CI: 2.62–2.84) for nonselective NSAIDs and 2.17 (95% CI: 1.83–2.57) for celecoxib. The OR reached 3.05 for the use of acetic acid derivatives. Compared with the oral forms, significantly higher risks were seen in parenteral NSAID use (OR: 8.66, 95% CI: 6.12–20.19). NSAIDs should be prescribed with caution, especially for those in ESRD high-risk groups. PMID:26402800

  16. In vitro and in vivo antioxidant, cytotoxic, and anti-chronic inflammatory arthritic effect of selenium nanoparticles.

    PubMed

    Malhotra, Sonam; Welling, M N; Mantri, S B; Desai, Krutika

    2016-07-01

    The toxicity of selenium (Se) as an antioxidant supplement in the treatment of arthritis is debatable. In this study, Dextrin stabilized Se nanoparticles (SeNP) of size 64 nm ± 0.158 were used to explore its effects as a potent antioxidant with reduced toxicity in both in vitro and in vivo. In vitro toxicity of SeNP was determined using cytotoxicity assay. In vitro interactions of SeNP with DNA and protein was established. Subacute toxicity of SeNP was studied. Wistar rats with complete freunds adjuvant induced arthritis were used. Various concentrations of SeNP per kg body weight were fed orally daily upto to 21 days. Arthritic profile based on paw swelling, histopathological changes in joints, blood indices, and antioxidant enzymes level in organs such as liver, kidney, and spleen were investigated. Dextrin-SeNP when interacted with NIH-3T3 cells showed 15% cytotoxicity at 100 µg/mL whereas, bulk Se showed 95% at the same concentration. SeNP at 250 µg/mL showed protective effect on DNA. Interaction of SeNP with BSA showed increase in quenching of BSA fluorescence. SeNP did not show any subacute toxicity at concentration as high as 5 mg/kg b.w. in Wistar rats. SeNP at a concentration of 250 µg/kg b.w. acted as potent anti-inflammatory agent and significantly reduced (p < 0.05) arthritis induced parameters. The enzymatic antioxidant levels in liver, kidney, and spleen were restored significantly (p < 0.05) at 500 µg/kg b.w. while CRP was regained to normal at concentration of 100 µg/kg b.w. concluding SeNP at 500 µg/kg b.w. can be a potential antiarthritic drug supplement. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 993-1003, 2016. PMID:25994972

  17. Comorbidity and Inflammatory Markers May Contribute to Predict Mortality of High-Risk Patients With Chronic Obstructive Pulmonary Disease Exacerbation

    PubMed Central

    Kim, Yu Jin; Lim, Byeongwoo; Kyung, Sun Young; Park, Jeong-woong; Jeong, Sung Hwan

    2016-01-01

    Background Acute exacerbation of chronic obstructive pulmonary disease (COPD) causes not only an accelerated disease progression, but also an increased mortality rate. The purpose of this study was to analyze the factors associated with clinical features, comorbidities and mortality in patients at high risk for acute COPD exacerbation who had been hospitalized at least once in a year. Methods The study enrolled 606 patients who had been diagnosed with and were being treated for COPD at university affiliated hospital. Among them, there were 61 patients at high risk for acute exacerbation of COPD who had been hospitalized at least once in a year. A retrospective analysis was conducted to examine the factors affecting mortality. The analysis divided the patients into non-survivor and survivor groups, and reviewed their medical records for clinical aspects, comorbidities, pulmonary function tests and blood tests. Results In the high-risk group, the number of comorbidities at diagnosis (P = 0.020) and the Charlson comorbidity index value (P = 0.018) were higher in the non-survivor group than in the survivor group. During hospitalization, the non-survivor group had a significantly higher neutrophil (%) and a significantly lower lymphocyte (%) in complete blood count. Under stable conditions, the high-sensitivity C-reactive protein (hsCRP) concentration in blood plasma and neutrophil (%) were significantly higher (P = 0.025 and P = 0.036), while the lymphocyte (%) was significantly lower (P = 0.005) in the non-survivor group. A pulmonary function test revealed no statistically significant differences between the two groups. Conclusion The number of comorbidities, neutrophil (%), lymphocyte (%) in complete blood cell (CBC) and hsCRP in blood plasma concentration among the groups at high risk for COPD exacerbation are associated with increased mortality. PMID:27298662

  18. Haemostatic and inflammatory biomarkers in advanced chronic heart failure: role of oral anticoagulants and successful heart transplantation.

    PubMed

    Cugno, Massimo; Mari, Daniela; Meroni, Pier Luigi; Gronda, Edoardo; Vicari, Francesco; Frigerio, Maria; Coppola, Raffaella; Bottasso, Bianca; Borghi, Maria Orietta; Gregorini, Luisa

    2004-07-01

    Advanced chronic heart failure (CHF) is associated with abnormal haemostasis and inflammation, but it is not known how these abnormalities are related, whether they are modified by oral anticoagulants (OAT), or if they persist after successful heart transplantation. We studied 25 patients with CHF (New York Heart Association class IV, 10 of whom underwent heart transplantation) and 25 age- and sex-matched healthy controls by measuring their plasma levels of prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin (TAT) complexes, tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), D-dimer, factor VII (FVII), fibrinogen, von Willebrand factor (VWF), tumour necrosis factor (TNF), soluble TNF receptor II (sTNFRII), interleukin 6 (IL-6), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), endothelial-selectin (E-selectin) and thrombomodulin. CHF patients had higher plasma levels of TAT, D-dimer, t-PA, fibrinogen, VWF, TNF, IL-6, sTNFRII, sVCAM-1 (P = 0.0001), sICAM-1 (P = 0.003) and thrombomodulin (P = 0.007) than controls. There were significant correlations (r = 0.414-0.595) between coagulation, fibrinolysis, endothelial dysfunction and inflammation parameters, which were lower in those patients treated with OATs. Heart transplantation led to reductions in fibrinogen (P = 0.001), VWF (P = 0.05), D-dimer (P = 0.05) and IL-6 levels (P = 0.05), but all the parameters remained significantly higher (P = 0.01-0.0001) than in the controls. Advanced CHF is associated with coagulation activation, endothelial dysfunction and increased proinflammatory cytokine levels. Most of these abnormalities parallel each other, tend to normalize in patients treated with OATs and, although reduced, persist in patients undergoing successful heart transplantation, despite the absence of clinical signs of CHF. PMID:15198737

  19. The role of mononuclear cell tissue factor and inflammatory cytokines in patients with chronic thromboembolic pulmonary hypertension.

    PubMed

    Yang, Minxia; Deng, Chaosheng; Wu, Dawen; Zhong, Zhanghua; Lv, Xiaoting; Huang, Zhihua; Lian, Ningfang; Liu, Kaixiong; Zhang, Qiaoxian

    2016-07-01

    Thrombosis and inflammation are two major factors underlying chronic thromboembolic pulmonary hypertension (CTEPH). Tissue factor (TF), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein 1 (MCP-1) may play critical roles in the process of CTEPH thrombosis and pulmonary vascular remodeling. Ten patients with a confirmed diagnosis of CTEPH, 20 patients with acute pulmonary thromboembolism and 15 patients with other types of pulmonary hypertension were enrolled in this study, along with 20 healthy subjects as the control group. The immunoturbidimetric method was used to determine the plasma content of CRP. The plasma levels of TNF-α, MCP-1, and TF antigen were measured by an enzyme-linked immunosorbent assay, and TF activity was measured by the chromogenic substrate method. Percoll density gradient centrifugation was used to separate peripheral blood mononuclear cells from plasma. The level of monocyte TF mRNA was examined by reverse transcriptase-polymerase chain reaction. The correlations between all indices described above were analyzed. In CTEPH patients, the expression of CRP, TNF-α, and MCP-1 was significantly higher than that in controls (P < 0.05). The levels of TF activity, TF antigen, and TF mRNA in monocyte cells were increased in CTEPH patients when compared with control subjects, but only the TF antigen and TF mRNA levels were significantly different (P < 0.05). In CTEPH patients, levels of CRP, MCP-1, and TNF-α significantly correlated with the level of TF antigen in plasma. TF gene expression was increased in patients with CTEPH, suggesting that blood-borne TF mainly comes from mononuclear cells. TF expression significantly correlated with levels of CRP, TNF-α and MCP-1. These factors may play an important role in the development of CTEPH via the inflammation-coagulation-thrombosis cycle. PMID:26667361

  20. Postural Orthostatic Tachycardia With Chronic Fatigue After HPV Vaccination as Part of the “Autoimmune/Auto-inflammatory Syndrome Induced by Adjuvants”

    PubMed Central

    Tomljenovic, Lucija; Colafrancesco, Serena; Perricone, Carlo

    2014-01-01

    We report the case of a 14-year-old girl who developed postural orthostatic tachycardia syndrome (POTS) with chronic fatigue 2 months following Gardasil vaccination. The patient suffered from persistent headaches, dizziness, recurrent syncope, poor motor coordination, weakness, fatigue, myalgias, numbness, tachycardia, dyspnea, visual disturbances, phonophobia, cognitive impairment, insomnia, gastrointestinal disturbances, and a weight loss of 20 pounds. The psychiatric evaluation ruled out the possibility that her symptoms were psychogenic or related to anxiety disorders. Furthermore, the patient tested positive for ANA (1:1280), lupus anticoagulant, and antiphospholipid. On clinical examination she presented livedo reticularis and was diagnosed with Raynaud’s syndrome. This case fulfills the criteria for the autoimmune/auto-inflammatory syndrome induced by adjuvants (ASIA). Because human papillomavirus vaccination is universally recommended to teenagers and because POTS frequently results in long-term disabilities (as was the case in our patient), a thorough follow-up of patients who present with relevant complaints after vaccination is strongly recommended. PMID:26425598

  1. Cost-utility of Intravenous Immunoglobulin (IVIG) compared with corticosteroids for the treatment of Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) in Canada

    PubMed Central

    2010-01-01

    Objectives Intravenous immunoglobulin (IVIG) has demonstrated improvement in chronic inflammatory demyelinating polyneuropathy (CIDP) patients in placebo controlled trials. However, IVIG is also much more expensive than alternative treatments such as corticosteroids. The objective of the paper is to evaluate, from a Canadian perspective, the cost-effectiveness of IVIG compared to corticosteroid treatment of CIDP. Methods A markov model was used to evaluate the costs and QALYs for IVIG and corticosteroids over 5 years of treatment for CIDP. Patients initially responding to IVIG could remain a responder or relapse every 12 week model cycle. Non-responding IVIG patients were assumed to be switched to corticosteroids. Patients on corticosteroids were at risk of a number of adverse events (fracture, diabetes, glaucoma, cataract, serious infection) in each cycle. Results Over the 5 year time horizon, the model estimated the incremental costs and QALYs of IVIG treatment compared to corticosteroid treatment to be $124,065 and 0.177 respectively. The incremental cost per QALY gained of IVIG was estimated to be $687,287. The cost per QALY of IVIG was sensitive to the assumptions regarding frequency and dosing of maintenance IVIG. Conclusions Based on common willingness to pay thresholds, IVIG would not be perceived as a cost effective treatment for CIDP. PMID:20565778

  2. IL17 Functions through the Novel REG3β-JAK2-STAT3 Inflammatory Pathway to Promote the Transition from Chronic Pancreatitis to Pancreatic Cancer.

    PubMed

    Loncle, Celine; Bonjoch, Laia; Folch-Puy, Emma; Lopez-Millan, Maria Belen; Lac, Sophie; Molejon, Maria Inés; Chuluyan, Eduardo; Cordelier, Pierre; Dubus, Pierre; Lomberk, Gwen; Urrutia, Raul; Closa, Daniel; Iovanna, Juan L

    2015-11-15

    Pancreatic ductal adenocarcinoma (PDAC) offers an optimal model for discovering "druggable" molecular pathways that participate in inflammation-associated cancer development. Chronic pancreatitis, a common prolonged inflammatory disease, behaves as a well-known premalignant condition that contributes to PDAC development. Although the mechanisms underlying the pancreatitis-to-cancer transition remain to be fully elucidated, emerging evidence supports the hypothesis that the actions of proinflammatory mediators on cells harboring Kras mutations promote neoplastic transformation. Recent elegant studies demonstrated that the IL17 pathway mediates this phenomenon and can be targeted with antibodies, but the downstream mechanisms by which IL17 functions during this transition are currently unclear. In this study, we demonstrate that IL17 induces the expression of REG3β, a well-known mediator of pancreatitis, during acinar-to-ductal metaplasia and in early pancreatic intraepithelial neoplasia (PanIN) lesions. Furthermore, we found that REG3β promotes cell growth and decreases sensitivity to cell death through activation of the gp130-JAK2-STAT3-dependent pathway. Genetic inactivation of REG3β in the context of oncogenic Kras-driven PDAC resulted in reduced PanIN formation, an effect that could be rescued by administration of exogenous REG3β. Taken together, our findings provide mechanistic insight into the pathways underlying inflammation-associated pancreatic cancer, revealing a dual and contextual pathophysiologic role for REG3β during pancreatitis and PDAC initiation. PMID:26404002

  3. Combined inhibition of PDE4 and PI3Kδ modulates the inflammatory component involved in the progression of chronic obstructive pulmonary disease.

    PubMed

    Dinavahi, S S; Nyayapathy, S; Perumal, Y; Dharmarajan, S; Viswanadha, S

    2014-04-01

    Chronic Obstructive Pulmonary Disease (COPD) represents a group of disorders with several underlying causes that hamper airflow into the lungs. Despite current intervention therapies, COPD remains a disease with a significant unmet medical need. Treatment with Phosphodiesterase (PDE) 4 inhibitors results in modest efficacy at clinically relevant doses. The objective of the current study is to evaluate the combination of a PDE4 (Roflumilast) and a Phosphoinositide-3-kinase (PI3K) δ (IC87114) inhibitor for their therapeutic potential in diminishing the inflammatory response associated with COPD. Due to their divergent and independent pathways, we hypothesize that the combination would be efficacious at low concentrations in an in vitro setting. Inhibition of TNFα, pAkt, MMP-9 in differentiated U937 macrophages upon stimulation with LPS/CSE was determined. Neutrophil functionality manifested by a modulation of elastase activity was estimated. Protective effect of drug combination on CSE induced apoptosis of lung epithelial cells was also determined. Data demonstrated that the combination of Roflumilast and IC87114 reduced TNFα, pAkt and MMP-9 at nanomolar concentrations and was several fold potent than either of the compounds alone. Inhibition of neutrophil elastase was also increased significantly with the combination along with a better protection against CSE induced apoptosis in alveolar epithelial cells, thereby providing a rationale for their evaluation in COPD patients. PMID:24105104

  4. Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) associated to hereditary neuropathy with liability to pressure palsies (HNPP) and revealed after influenza AH1N1 vaccination.

    PubMed

    Remiche, Gauthier; Abramowicz, Marc; Mavroudakis, Nicolas

    2013-12-01

    Neurological complications of AH1N1 vaccination such as Guillain-Barré syndrome were described in the previous years. Several reports suggest that hereditary neuropathies may be a predisposing factor for immune-mediated neuropathies. We report the case of a 54-year-old female who developed chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) 5 weeks after AH1N1 vaccination. She had no previous neurological history, but neurophysiological features led us to suspect an underlying hereditary neuropathy. PMP22 gene analysis showed a typical deletion, confirming the diagnosis of hereditary neuropathy with liability to pressure palsies (HNPP). We observed a significant clinical and neurophysiological improvement of the neuropathy after intravenous immunoglobulin treatment. This is, to our knowledge, the first reported case of CIDP potentially triggered by AH1N1 vaccination. This and previous observations suggest that genetic-determined neuropathies could predispose to the occurrence of immune-mediated neuropathies. One must recall the possibility of a superimposed hereditary neuropathy like HNPP in patients with a clinical presentation of CIDP, especially when positive family history or unexpected neurophysiological features are present. PMID:24146347

  5. Anti-inflammatory/regulatory cytokine microenvironment mediated by IL-4 and IL-10 coordinates the immune response in hemophilia A patients infected chronically with hepatitis C virus.

    PubMed

    Pimentel, João Paulo; Chaves, Daniel Gonçalves; Araújo, Ana Ruth Silva; de Araújo, Erbênia Maria Martins; da Silva Fraporti, Liziara; Neves, Walter Luiz Lima; Tarragô, Andrea Monteiro; Torres, Katia Luz; Gentz, Solange Henschke Lima; Teixeira-Carvalho, Andréa; Martins-Filho, Olindo Assis; Malheiro, Adriana

    2013-06-01

    In the past decades patients with hemophilia were infected commonly by hepatitis C virus (HCV) and a significant number of patients are infected chronically. Focusing on the role of the immune system for controlling and or maintaining HCV infection, the leukocyte and cytokine profiles of peripheral blood from hemophilia A patients and other patients with and without HCV infection were studied. The results demonstrated that hemophilia A is characterized by a general state of circulating leukocytes activation along with an overall increase in the frequency of IL-6 and IL-10 with decrease of IL-8 and IL-12. HCV infection of patients with hemophilia A does not influence further the activation state of circulating leukocytes but is accompanied by lower levels of alanine transaminase (ALT) and a prominent anti-inflammatory/regulatory serum cytokine pattern, mediated by IL-4 and IL-10. Additionally, the results demonstrated that hemophilia A patients infected with HCV displaying No/Low antibody response to C33c and C22 have significant lower viral load and higher serum levels of IL-12 and IL-4. This finding suggests that the differential RIBA reactivity to C33c/C22 HCV core proteins may have a putative value as a prognostic biomarker for the infection in hemophilia A patients. PMID:23591975

  6. Dimeric Le(a) (Le(a)-on-Le(a)) status of beta-haptoglobin in sera of colon cancer, chronic inflammatory disease and normal subjects.

    PubMed

    Park, Seung-Yeol; Yoon, Seon-Joo; Hakomori, Sen-Itiroh; Kim, Jin-Man; Kim, Ji-Yeon; Bernert, Bradford; Ullman, Thomas; Itzkowitz, Steven H; Kim, Jung Hoe

    2010-05-01

    The glycosyl epitope dimeric Lea (Lea-on-Lea), defined by mouse monoclonal antibody NCC-ST-421, was identified previously as tumor-associated antigen, expressed highly in various human cancer tissues and cell lines derived therefrom, but with minimal expression in various normal tissues. In the present study, we observed clearly higher expression of this epitope, defined by ST421, in beta-haptoglobin (beta-Hap) from sera of patients with colorectal cancer, compared to normal, healthy subjects or patients with chronic inflammatory processes (Crohn's disease, ulcerative colitis). We focused, therefore, on biochemical characterization of glycosyl epitope status expressed in beta-Hap. We concluded that the dimeric Lea epitope is carried by O-linked but not by N-linked structure, based on the following observations: i) Treatment of beta-Hap with alpha-L-fucosidase reduced its reactivity with ST421, but did not affect its reactivity with anti-Hap antibody. In contrast, treatment of purified beta-Hap with PNGase F, which releases N-linked glycans, had no effect on reactivity with ST421, but changed molecular mass from 40 kDa to 30 kDa. ii) Strong reactivity of Colo205 supernatant with ST421 was reduced clearly by pre-incubation of cells with benzyl-alpha-GalNAc. PMID:20372805

  7. Anti-inflammatory effects of potato extract on a rat model of cigarette smoke–induced chronic obstructive pulmonary disease

    PubMed Central

    Xu, Gui Hua; Shen, Jie; Sun, Peng; Yang, Min Li; Zhao, Peng Wei; Niu, Yan; Lu, Jing Kun; Wang, Zhi Qiang; Gao, Chao; Han, Xue; Liu, Lei Lei; Liu, Chen Chen; Cong, Zhang Yue

    2015-01-01

    Highlights: (1) Potato extract (PE) exhibits non-toxic effects on mice. (2) Cigarette smoke (CS)–induced COPD rats exhibit significant thickened and disordered lung markings. (3) PE could improve the histopathological symptoms of lung tissue in COPD. (4) PE could increase the expression of IL-10 and reduce the expression of TNF-α and G-CSF in COPD rats. Objective This study aimed to evaluate the therapeutic effects of potato extract (PE) on cigarette smoke (CS)–induced chronic obstructive pulmonary disease (COPD). Methods PE was first prepared by frozen centrifugation, and its amino acid composition was detected. Toxicity of PE was analyzed by changes in morphology, behavior, routine blood indexes, and biochemical criteria of mice. Then, the COPD rat model was established by CS exposure, and PE, doxofylline, and prednisolone acetate were used to treat these rats. After 45 days of treatment, the morphology and behavior of rats were recorded. In addition, the histopathology of lung tissue was evaluated by chest x-ray and hematoxylin and eosin staining. The expression of interleukine-10 (IL-10), tumor necrosis factor-α (TNF-α), and granulocyte colony-stimulating factor (G-CSF) was detected in serum and lung tissue by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry, respectively. Results Various amino acids were identified in PE, and no toxicity was exhibited in mice. The CS-induced COPD rat model was successfully established, which exhibited significant thickened and disordered lung markings on 90% of the rats. After administering doxofylline and prednisolone acetate, inflammation symptoms were improved. However, side effects such as emaciation, weakness, and loosening of teeth appeared. In the PE group, obviously improved histopathology was observed in lung tissues. Meanwhile, it was revealed that PE could increase the expression of IL-10 and reduce the expression of TNF-α and G-CSF in COPD rats, and doxofylline and prednisolone acetate

  8. Provenance management in Swift with implementation details.

    SciTech Connect

    Gadelha, L. M. R; Clifford, B.; Mattoso, M.; Wilde, M.; Foster, I.

    2011-04-01

    The Swift parallel scripting language allows for the specification, execution and analysis of large-scale computations in parallel and distributed environments. It incorporates a data model for recording and querying provenance information. In this article we describe these capabilities and evaluate interoperability with other systems through the use of the Open Provenance Model. We describe Swift's provenance data model and compare it to the Open Provenance Model. We also describe and evaluate activities performed within the Third Provenance Challenge, which consisted of implementing a specific scientific workflow, capturing and recording provenance information of its execution, performing provenance queries, and exchanging provenance information with other systems. Finally, we propose improvements to both the Open Provenance Model and Swift's provenance system.

  9. File level provenance tracking in CMS

    SciTech Connect

    Jones, C.D.; Kowalkowski, J.; Paterno, M.; Sexton-Kennedy, L.; Tanenbaum, W.; Riley, D.S.; /Cornell U., LEPP

    2009-05-01

    The CMS off-line framework stores provenance information within CMS's standard ROOT event data files. The provenance information is used to track how each data product was constructed, including what other data products were read to do the construction. We will present how the framework gathers the provenance information, the efforts necessary to minimize the space used to store the provenance in the file and the tools that will be available to use the provenance.

  10. The ion channel transient receptor potential melastatin-2 does not play a role in inflammatory mouse models of chronic obstructive pulmonary diseases

    PubMed Central

    2012-01-01

    Background There is strong evidence that oxidative stress is associated with the pathogenesis of chronic obstructive pulmonary disease (COPD). The transient receptor potential melastatin-2 (TRPM2) is an oxidative stress sensing channel that is expressed in a number of inflammatory cells and therefore it has been suggested that inhibition of TRPM2 could lead to a beneficial effect in COPD patients. In this study, we have investigated the role of TRPM2 in a variety of mouse models of oxidative stress and COPD using TRPM2-deficent mice. Methods Mice were exposed to ozone (3 ppm for 4 h) or lipopolysaccharide (LPS, 0.3 mg/kg, intranasaly). In another model, mice were exposed to tobacco smoke (750 μg/l total wet particulate matter) for 30 min twice a day on three consecutive days. For the exacerbation model, the smoke exposure on the morning of day 3 animals was replaced with intranasal administration of LPS (0.3 mg/kg). Animals were killed 3 and 24 h after the challenge (ozone and LPS model) or 18 h after the last tobacco smoke exposure. In vitro neutrophil chemotaxis and monocyte activation were also studied using cells isolated from wild type and TRPM2-deficient animals. Statistical significance for the in vivo data (P < 0.05) was determined using analysis of variance with Kruskal-Wallis and Dunns multiple comparison test. Results In all models studied, no difference in the bronchoalveolar lavage inflammation could be evidenced when comparing wild type and TRPM2-deficient mice. In addition, no difference could be seen in the lung inflammation as assessed by the measurement of various cytokines/chemokines. Similarly in various in vitro cellular activation assays using isolated neutrophils and monocytes no significant differences could be observed when comparing wild type and TRPM2-deficient mice. Discussion We have shown, in all the models tested, no difference in the development of airway inflammation or cell activation between TRPM2-deficient mice and their wild

  11. Transcriptome Analysis of Peripheral Blood in Chronic Inflammatory Demyelinating Polyradiculoneuropathy Patients Identifies TNFR1 and TLR Pathways in the IVIg Response

    PubMed Central

    Richard, Alexandra; Corvol, Jean-Christophe; Debs, Rabab; Reach, Pauline; Tahiri, Khadija; Carpentier, Wassila; Gueguen, Justine; Guillemot, Vincent; Labeyrie, Céline; Adams, David; Viala, Karine; Cohen Aubart, Fleur

    2016-01-01

    Abstract We have studied the response to intravenous immunoglobulins (IVIg) by a transcriptomic approach in 11 chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) patients (CIDP duration = 6 [0.83–6.5] years). RNA was extracted from cells in whole blood collected before and 3 weeks after IVIg treatment, and hybridized on Illumina chips. After RNA quality controls, gene expression was analyzed using statistical tests fitted for microarrays (R software, limma package), and a pathway analysis was performed using DAVID software. We identified 52 genes with expression that varied significantly after IVIg (fold change [FC] > 1.2, P < 0.001, false discovery rate [FDR] <0.05). Among these 52 genes, 7 were related to immunity, 3 were related to the tumor necrosis factor (TNF)-α receptor 1 (TNFR1) pathway (inhibitor of caspase-activated DNase (ICAD): FC = 1.8, P = 1.7E-7, FDR = 0.004; p21 protein-activated kinase 2 [PAK2]: FC = 1.66, P = 2.6E-5, FDR = 0.03; TNF-α-induced protein 8-like protein 1 [TNFAIP8L1]: P = 1.00E-05, FDR = 0.026), and 2 were related to Toll-like receptors (TLRs), especially TLRs 7 and 9, and were implicated in autoimmunity. These genes were UNC93B1 (FC = 1.6, P = 2E-5, FDR = 0.03), which transports TLRs 7 and 9 to the endolysosomes, and RNF216 (FC = 1.5, P = 1E-05, FDR = 0.03), which promotes TLR 9 degradation. Pathway analysis showed that the TNFR1 pathway was significantly lessened by IVIg (enrichment score = 24, Fischer exact test = 0.003). TNF-α gene expression was higher in responder patients than in nonresponders; however, it decreased after IVIg in responders (P = 0.04), but remained stable in nonresponders. Our data suggest the actions of IVIg on the TNFR1 pathway and an original mechanism involving innate immunity through TLRs in CIDP pathophysiology and the response to IVIg. We conclude that responder patients have stronger inflammatory activity

  12. Transcriptome Analysis of Peripheral Blood in Chronic Inflammatory Demyelinating Polyradiculoneuropathy Patients Identifies TNFR1 and TLR Pathways in the IVIg Response.

    PubMed

    Richard, Alexandra; Corvol, Jean-Christophe; Debs, Rabab; Reach, Pauline; Tahiri, Khadija; Carpentier, Wassila; Gueguen, Justine; Guillemot, Vincent; Labeyrie, Céline; Adams, David; Viala, Karine; Cohen Aubart, Fleur

    2016-05-01

    We have studied the response to intravenous immunoglobulins (IVIg) by a transcriptomic approach in 11 chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) patients (CIDP duration = 6 [0.83-6.5] years). RNA was extracted from cells in whole blood collected before and 3 weeks after IVIg treatment, and hybridized on Illumina chips. After RNA quality controls, gene expression was analyzed using statistical tests fitted for microarrays (R software, limma package), and a pathway analysis was performed using DAVID software. We identified 52 genes with expression that varied significantly after IVIg (fold change [FC] > 1.2, P < 0.001, false discovery rate [FDR] <0.05). Among these 52 genes, 7 were related to immunity, 3 were related to the tumor necrosis factor (TNF)-α receptor 1 (TNFR1) pathway (inhibitor of caspase-activated DNase (ICAD): FC = 1.8, P = 1.7E-7, FDR = 0.004; p21 protein-activated kinase 2 [PAK2]: FC = 1.66, P = 2.6E-5, FDR = 0.03; TNF-α-induced protein 8-like protein 1 [TNFAIP8L1]: P = 1.00E-05, FDR = 0.026), and 2 were related to Toll-like receptors (TLRs), especially TLRs 7 and 9, and were implicated in autoimmunity. These genes were UNC93B1 (FC = 1.6, P = 2E-5, FDR = 0.03), which transports TLRs 7 and 9 to the endolysosomes, and RNF216 (FC = 1.5, P = 1E-05, FDR = 0.03), which promotes TLR 9 degradation. Pathway analysis showed that the TNFR1 pathway was significantly lessened by IVIg (enrichment score = 24, Fischer exact test = 0.003). TNF-α gene expression was higher in responder patients than in nonresponders; however, it decreased after IVIg in responders (P = 0.04), but remained stable in nonresponders. Our data suggest the actions of IVIg on the TNFR1 pathway and an original mechanism involving innate immunity through TLRs in CIDP pathophysiology and the response to IVIg. We conclude that responder patients have stronger inflammatory activity that is

  13. Curcumin in inflammatory diseases.

    PubMed

    Shehzad, Adeeb; Rehman, Gauhar; Lee, Young Sup

    2013-01-01

    Curcumin (diferuloylmethane), a yellow coloring agent extracted from turmeric is also used as a remedy for the treatment and prevention of inflammatory diseases. Acute and chronic inflammation is a major factor in the progression of obesity, type II diabetes, arthritis, pancreatitis, cardiovascular, neurodegenerative and metabolic diseases, as well as certain types of cancer. Turmeric has a long history of use in Ayurvedic medicine for the treatment of inflammatory disorders. Recent studies on the efficacy and therapeutic applicability of turmeric have suggested that the active ingredient of tumeric is curcumin. Further, compelling evidence has shown that curcumin has the ability to inhibit inflammatory cell proliferation, invasion, and angiogenesis through multiple molecular targets and mechanisms of action. Curcumin is safe, non-toxic, and mediates its anti-inflammatory effects through the down-regulation of inflammatory transcription factors, cytokines, redox status, protein kinases, and enzymes that all promote inflammation. In addition, curcumin induces apoptosis through mitochondrial and receptor-mediated pathways, as well as activation of caspase cascades. In the current study, the anti-inflammatory effects of curcumin were evaluated relative to various chronic inflammatory diseases. Based on the available pharmacological data obtained from in vitro and in vivo research, as well as clinical trials, an opportunity exists to translate curcumin into clinics for the prevention of inflammatory diseases in the near future. PMID:23281076

  14. Anti-inflammatory effects of myrtol standardized and other essential oils on alveolar macrophages from patients with chronic obstructive pulmonary disease

    PubMed Central

    2009-01-01

    Introduction Myrtol standardized is established in the treatment of acute and chronic bronchitis and sinusitis. It increases mucociliar clearance and has muco-secretolytic effects. Additional anti-inflammatory and antioxidative properties have been confirmed for Myrtol standardized, eucalyptus oil, and orange oil in several in vitro studies. Objective The aim of this study was to prove the ability of essential oils to reduce cytokines release and reactive oxygen species (ROS) production derived from ex vivo cultured alveolar macrophages. Material and methods Alveolar macrophages from patients with chronic obstructive pulmonary disease (COPD, n = 26, GOLD III-IV) were pre-cultured with essential oils (10-3-10-8%) for 1 h and then stimulated with LPS (1 μg/ml). After 4 h and 20 h respectively a) cellular reactive oxygen species (ROS) using 2',7'-dichlorofluorescein (DCF), and b) TNF-α, IL-8, and GM-CSF secretion were quantified. Results In comparison with negative controls, pre-cultured Myrtol, eucalyptus oil and orange oil (10-4%) reduced in the LPS-activated alveolar macrophages ROS release significantly after 1+20 h as follows: Myrtol - 17.7% (P = 0.05), eucalyptus oil -21.8% (P < 0.01) and orange oil -23.6% (P < 0.01). Anti-oxidative efficacy was comparable to NAC (1 mmol/l). Essential oils also induced a TNF-α reduction: Myrtol (-37.3%, P < 0.001), eucalyptus oil (-26.8%, P < 0.01) and orange oil (-26.6%, P < 0.01). TNF-α reduction at 1+4 h and 1+20 h did not vary (Myrtol: -31.9% and -37.3% respectively, P = 0.372) indicating that this effect occurs early and cannot be further stimulated. Myrtol reduced the release of GMCSF by -35.7% and that of IL-8 only inconsiderably. Conclusions All essential oils tested have effective antioxidative properties in ex vivo cultured and LPS-stimulated alveolar macrophages. Additionally, Myrtol inhibited TNF-α and GM-CSF release best indicating additional potent anti-inflammator y activity. PMID:20156758

  15. Quantitative analysis of cellular inflammation after traumatic spinal cord injury: evidence for a multiphasic inflammatory response in the acute to chronic environment

    PubMed Central

    Beck, Kevin D.; Nguyen, Hal X.; Galvan, Manuel D.; Salazar, Desirée L.; Woodruff, Trent M.

    2010-01-01

    Traumatic injury to the central nervous system results in the disruption of the blood brain/spinal barrier, followed by the invasion of cells and other components of the immune system that can aggravate injury and affect subsequent repair and regeneration. Although studies of chronic neuroinflammation in the injured spinal cord of animals are clinically relevant to most patients living with traumatic injury to the brain or spinal cord, very little is known about chronic neuroinflammation, though several studies have tested the role of neuroinflammation in the acute period after injury. The present study characterizes a novel cell preparation method that assesses, quickly and effectively, the changes in the principal immune cell types by flow cytometry in the injured spinal cord, daily for the first 10 days and periodically up to 180 days after spinal cord injury. These data quantitatively demonstrate a novel time-dependent multiphasic response of cellular inflammation in the spinal cord after spinal cord injury and are verified by quantitative stereology of immunolabelled spinal cord sections at selected time points. The early phase of cellular inflammation is comprised principally of neutrophils (peaking 1 day post-injury), macrophages/microglia (peaking 7 days post-injury) and T cells (peaking 9 days post-injury). The late phase of cellular inflammation was detected after 14 days post-injury, peaked after 60 days post-injury and remained detectable throughout 180 days post-injury for all three cell types. Furthermore, the late phase of cellular inflammation (14–180 days post-injury) did not coincide with either further improvements, or new decrements, in open-field locomotor function after spinal cord injury. However, blockade of chemoattractant C5a-mediated inflammation after 14 days post-injury reduced locomotor recovery and myelination in the injured spinal cord, suggesting that the late inflammatory response serves a reparative function. Together, these

  16. Vitamin D and inflammatory diseases

    PubMed Central

    Yin, Kai; Agrawal, Devendra K

    2014-01-01

    Beyond its critical function in calcium homeostasis, vitamin D has recently been found to play an important role in the modulation of the immune/inflammation system via regulating the production of inflammatory cytokines and inhibiting the proliferation of proinflammatory cells, both of which are crucial for the pathogenesis of inflammatory diseases. Several studies have associated lower vitamin D status with increased risk and unfavorable outcome of acute infections. Vitamin D supplementation bolsters clinical responses to acute infection. Moreover, chronic inflammatory diseases, such as atherosclerosis-related cardiovascular disease, asthma, inflammatory bowel disease, chronic kidney disease, nonalcoholic fatty liver disease, and others, tend to have lower vitamin D status, which may play a pleiotropic role in the pathogenesis of the diseases. In this article, we review recent epidemiological and interventional studies of vitamin D in various inflammatory diseases. The potential mechanisms of vitamin D in regulating immune/inflammatory responses in inflammatory diseases are also discussed. PMID:24971027

  17. Increased Prevalence of Human Polyomavirus JC Viruria in Chronic Inflammatory Rheumatic Diseases Patients in Treatment with Anti-TNF α: A 18 Month Follow-Up Study.

    PubMed

    Rodio, Donatella Maria; Anzivino, Elena; Mischitelli, Monica; Bellizzi, Anna; Scrivo, Rossana; Scribano, Daniela; Conte, Gianlorenzo; Prezioso, Carla; Trancassini, Maria; Valesini, Guido; Palamara, Anna Teresa; Pietropaolo, Valeria

    2016-01-01

    Chronic inflammatory rheumatic diseases (CIRDs) are immune-mediated pathologies involving joints. To date, TNFα-blocking agents administration is the most promising therapy, although these treatments are associated with an increased Polyomavirus JC (JCPyV) reactivation, the etiological agent of the Progressive Multifocal Leukoencephalopathy (PML). The aim of this study was the recruitment and the analysis of a CIRDs cohort in order to investigate a possible correlation between JCPyV presence and the influence of anti-TNF-α agents on viral loads. Blood and urine samples were collected from 34 CIRDs subjects prior the first anti-TNF-α infusion (T0) and after 3 (T3), 6 (T6), 12 (T12), and 18 (T18) months. Results showed persistent JC viruria significantly higher than JC viremia throughout the 18 month follow-up study (p = 0.002). In JCPyV positive samples, the non-coding control region (NCCR) was analyzed. Results evidenced archetypal structures (type II-S) in all isolates with the exception of a sequence isolated from a plasma sample, that corresponds to the type II-R found in PML subjects. Finally, the viral protein 1 (VP1) genotyping was performed and results showed the prevalence of the European genotypes 1A, 1B, and 4. Since only few studies have been carried out to understand whether there is a PML risk in CIRDs population infected by JCPyV, this study contributes to enrich literature insight on JCPyV biology in this cluster. Further investigations are necessary in order to recognize the real impact of biologics on JCPyV life cycle and to identify possible and specific viral variants related to increased virulence in CIRDs patients. PMID:27242700

  18. Increased Prevalence of Human Polyomavirus JC Viruria in Chronic Inflammatory Rheumatic Diseases Patients in Treatment with Anti-TNF α: A 18 Month Follow-Up Study

    PubMed Central

    Rodio, Donatella Maria; Anzivino, Elena; Mischitelli, Monica; Bellizzi, Anna; Scrivo, Rossana; Scribano, Daniela; Conte, Gianlorenzo; Prezioso, Carla; Trancassini, Maria; Valesini, Guido; Palamara, Anna Teresa; Pietropaolo, Valeria

    2016-01-01

    Chronic inflammatory rheumatic diseases (CIRDs) are immune-mediated pathologies involving joints. To date, TNFα-blocking agents administration is the most promising therapy, although these treatments are associated with an increased Polyomavirus JC (JCPyV) reactivation, the etiological agent of the Progressive Multifocal Leukoencephalopathy (PML). The aim of this study was the recruitment and the analysis of a CIRDs cohort in order to investigate a possible correlation between JCPyV presence and the influence of anti-TNF-α agents on viral loads. Blood and urine samples were collected from 34 CIRDs subjects prior the first anti-TNF-α infusion (T0) and after 3 (T3), 6 (T6), 12 (T12), and 18 (T18) months. Results showed persistent JC viruria significantly higher than JC viremia throughout the 18 month follow-up study (p = 0.002). In JCPyV positive samples, the non-coding control region (NCCR) was analyzed. Results evidenced archetypal structures (type II-S) in all isolates with the exception of a sequence isolated from a plasma sample, that corresponds to the type II-R found in PML subjects. Finally, the viral protein 1 (VP1) genotyping was performed and results showed the prevalence of the European genotypes 1A, 1B, and 4. Since only few studies have been carried out to understand whether there is a PML risk in CIRDs population infected by JCPyV, this study contributes to enrich literature insight on JCPyV biology in this cluster. Further investigations are necessary in order to recognize the real impact of biologics on JCPyV life cycle and to identify possible and specific viral variants related to increased virulence in CIRDs patients. PMID:27242700

  19. The skin tissue is adversely affected by TNF-alpha blockers in patients with chronic inflammatory arthritis: a 5-year prospective analysis

    PubMed Central

    Machado, Natalia P.; dos Reis Neto, Edgard Torres; Soares, Maria Roberta M. P.; Freitas, Daniele S.; Porro, Adriana; Ciconelli, Rozana M.; Pinheiro, Marcelo M.

    2013-01-01

    OBJECTIVE: We evaluated the incidence of and the main risk factors associated with cutaneous adverse events in patients with chronic inflammatory arthritis following anti-TNF-α therapy. METHODS: A total of 257 patients with active arthritis who were taking TNF-α blockers, including 158 patients with rheumatoid arthritis, 87 with ankylosing spondylitis and 12 with psoriatic arthritis, were enrolled in a 5-year prospective analysis. Patients with overlapping or other rheumatic diseases were excluded. Anthropometric, socioeconomic, demographic and clinical data were evaluated, including the Disease Activity Score-28, Bath Ankylosing Spondylitis Disease Activity Index and Psoriasis Area Severity Index. Skin conditions were evaluated by two dermatology experts, and in doubtful cases, skin lesion biopsies were performed. Associations between adverse cutaneous events and clinical, demographic and epidemiological variables were determined using the chi-square test, and logistic regression analyses were performed to identify risk factors. The significance level was set at p<0.05. RESULTS: After 60 months of follow-up, 71 adverse events (73.85/1000 patient-years) were observed, of which allergic and immune-mediated phenomena were the most frequent events, followed by infectious conditions involving bacterial (47.1%), parasitic (23.5%), fungal (20.6%) and viral (8.8%) agents. CONCLUSION: The skin is significantly affected by adverse reactions resulting from the use of TNF-α blockers, and the main risk factors for cutaneous events were advanced age, female sex, a diagnosis of rheumatoid arthritis, disease activity and the use of infliximab. PMID:24141833

  20. Incidence of active mycobacterial infections in Brazilian patients with chronic inflammatory arthritis and negative evaluation for latent tuberculosis infection at baseline - A longitudinal analysis after using TNFα blockers

    PubMed Central

    Gomes, Carina Mori Frade; Terreri, Maria Teresa; de Moraes-Pinto, Maria Isabel; Barbosa, Cássia; Machado, Natália Pereira; Melo, Maria Roberta; Pinheiro, Marcelo Medeiros

    2015-01-01

    Several studies point to the increased risk of reactivation of latent tuberculosis infection (LTBI) in patients with chronic inflammatory arthritis (CIAs) after using tumour necrosis factor (TNF)α blockers. To study the incidence of active mycobacterial infections (aMI) in patients starting TNF α blockers, 262 patients were included in this study: 109 with rheumatoid arthritis (RA), 93 with ankylosing spondylitis (AS), 44 with juvenile idiopathic arthritis (JIA) and 16 with psoriatic arthritis (PsA). All patients had indication for anti-TNF α therapy. Epidemiologic and clinical data were evaluated and a simple X-ray and tuberculin skin test (TST) were performed. The control group included 215 healthy individuals. The follow-up was 48 months to identify cases of aMI. TST positivity was higher in patients with AS (37.6%) than in RA (12.8%), PsA (18.8%) and JIA (6.8%) (p < 0.001). In the control group, TST positivity was 32.7%. Nine (3.43%) patients were diagnosed with aMI. The overall incidence rate of aMI was 86.93/100,000 person-years [95% confidence interval (CI) 23.6-217.9] for patients and 35.79/100,000 person-years (95% CI 12.4-69.6) for control group (p < 0.001). All patients who developed aMI had no evidence of LTBI at the baseline evaluation. Patients with CIA starting TNF α blockers and no evidence of LTBI at baseline, particularly with nonreactive TST, may have higher risk of aMI. PMID:26560983

  1. Intrathecal SRT1720, a SIRT1 agonist, exerts anti-hyperalgesic and anti-inflammatory effects on chronic constriction injury-induced neuropathic pain in rats

    PubMed Central

    Lv, Chen; Hu, Hong-Yi; Zhao, Li; Zheng, Hui; Luo, Xian-Zhe; Zhang, Juan

    2015-01-01

    Neuropathic pain is caused by lesion or inflammation of the nervous system and characterized by the symptoms of allodynia, hyperalgesia and spontaneous pain. SIRT1 (Sir2) is a NAD-dependent deacetylase and is reported to regulate a wide variety of cellular processes including inflammation, aging and lifespan extension. Nevertheless, the role of SIRT1 in neuropathic pain is not fully understood. The present study was intended to detect the effect of intrathecal SRT1720, a SIRT1 agonist, using quantitative real-time PCR and western blot analysis over time in rats following chronic constriction injury (CCI) or sham surgery. In addition, the effect of intrathecal injection of SRT1720 on thermal hyperalgesia and mechanical allodynia was evaluated in CCI rats. It was found that daily intrathecal injection of SRT1720 before and 1, 3, 5, 7 days after CCI surgery produced a transient inhibitory effect on thermal hyperalgesia and mechanical allodynia in CCI rats. In addition, an intrathecal injection of STR1-siRNA before SRT1720 administration reversed the anti-nociceptive effect of SRT1720. Furthermore, intrathecal injection of SRT1720 significantly down-regulated the expression of mammalian target of rapamycin (mROT), NF-κB and inflammatory cytokines, such as IL-6, TNF-α and iNOS mRNA. These data indicate that intrathecal SRT1720 may be an alternative strategy for the treatment of neuropathic pain. Our findings suggest that intrathecal SRT1720, a SIRT1 agonist, exerts antihyperalgesic and antiinflammatory effects on CCI-induced neuropathic pain in rats. PMID:26221253

  2. Use of Nonsteroidal Anti-Inflammatory Drugs and Risk of Chronic Kidney Disease in Subjects With Hypertension: Nationwide Longitudinal Cohort Study.

    PubMed

    Hsu, Chih-Cheng; Wang, Hongjian; Hsu, Yueh-Han; Chuang, Shao-Yuan; Huang, Ya-Wen; Chang, Yu-Kang; Liu, Jia-Sin; Hsiung, Chao A; Tsai, Hui-Ju

    2015-09-01

    Limited studies have examined the effects of nonsteroidal anti-inflammatory drug (NSAID) use on the risk of chronic kidney disease (CKD), especially in subjects with hypertension. Using National Health Insurance claims data in Taiwan, we conducted a propensity score-matched cohort study to investigate the relationship between NSAID use and CKD in subjects with hypertension. A total of 31976 subjects were included in this study: subjects not taking any NSAIDs in 2007 (n=10782); subjects taking NSAIDs for 1 to 89 days in 2007 (n=10605); and subjects taking NSAIDs for ≥90 days in 2007 (n=10589). We performed multivariable proportional hazard models to determine the relationship between NSAID use and CKD. The results showed that NSAID use was associated with a 1.18-fold increased risk of CKD in subjects taking NSAIDs for 1 to 89 days; and a 1.32-fold increased risk of CKD in hypertension subjects taking NSAIDs for ≥90 days, compared with subjects not taking any NSAIDs, after controlling for the confounding factors. In subgroup analyses, subjects taking NSAIDs for ≥90 days, >1 defined daily dose per day or taking NSAIDs >15 cumulative defined daily doses had a greater risk of CKD than subjects not taking any NSAID, but not for congestive heart failure, stroke, cancer, osteoarthritis, or rheumatoid arthritis. These results provide supportive evidence that NSAID use is associated with increased risk of CKD in subjects with hypertension. It is important to closely monitor the effects of NSAID use, particularly in patients with hypertension, a susceptible population for CKD. PMID:26169048

  3. Bioengineered Colorectal Cancer Drugs: Orally Delivered Anti-Inflammatory Agents.

    PubMed

    Urbanska, Aleksandra Malgorzata; Zhang, Xiaoying; Prakash, Satya

    2015-07-01

    Intestinal inflammation is one of the major factors that increase colorectal cancer (CRC) incidence worldwide. Inflammation in the gastrointestinal tract is directly linked to tumor development at the early stages of the disease, thus a key issue toward the prevention and the treatment of colonic neoplasia. Thus, the use of anti-inflammatory drugs has emerged first as a strategy to reduce chronic inflammation in case of many inflammatory bowel diseases (IBD), but it has proven its efficacy by reducing the risk of colonic neoplasia. This comprehensive review highlights the role of chronic inflammation, mainly in IBD, in the development of CRC including molecular and immune mechanisms that have tumorigenic effects. Multiple lines of evidence indicate that several bioactive and phytochemical compounds used as anti-inflammatory drugs have also antitumoral attributes. The uses of orally delivered cytokines and small molecules, as well as key dietary supplementation as anti-inflammatory therapeutics are discussed. In addition, comprehensive knowledge about CRC and intestinal inflammation, and the importance of the intestinal mucosal wall as a mucosal immunological barrier that comes into play during interactions with gut microbiota (pathogens and commensal), luminal secretions (bile acids, and bacterial and epithelial metabolites), and ingested chemicals (food components, high fat content, heterocyclic amines, and low intake of dietary fiber) are underscored. The multifunctionality of several anti-inflammatory drugs opens a line for their application in the treatment and prevention not only in IBD but also in CRC. Current bioengineering approaches for oral delivery of anti-inflammatory agents including cytokines, genetically modified bacteria, or small molecule inhibitors of inflammation directly contribute to the early management of CRC. Limitations of the current therapeutics, which stem from the lack of complete understanding of the complex molecular interactions

  4. [Ultrasonographic diagnosis of inflammatory neuropathies].

    PubMed

    Sugimoto, Takamichi; Ochi, Kazuhide; Hosomi, Naohisa; Matsumoto, Masayasu

    2014-03-01

    Ultrasonographic nerve enlargement has primarily been reported in patients with inflammatory neuropathies such as chronic inflammatory demyelinating polyneuropathy (CIDP), multifocal motor neuropathy, Guillain-Barre syndrome, vasculitic neuropathy and leprosy. Nerve ultrasonography is a promising diagnostic supportive tool for inflammatory neuropathies. The ultrasonographic findings that are currently useful are 1) nerve enlargement primarily suggests the existence of inflammatory or demyelinating neuropathies and 2) for patients with CIDP or demyelinating Charcot-Marie-Tooth disease, the pattern of nerve enlargement is noted, and this pattern is useful for discriminating between these diseases. More precise evidence of ultrasonographic findings for inflammatory neuropathies should be established in the future. PMID:24607946

  5. Prescribing patterns of non-steroidal anti-inflammatory drugs in chronic kidney disease patients in the South African private sector.

    PubMed

    Meuwesen, Willem P; du Plessis, Jesslee M; Burger, Johanita R; Lubbe, Martie S; Cockeran, Marike

    2016-08-01

    Background Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used pharmaceutical agents worldwide. NSAIDs are considered nephrotoxic and should therefore be used with caution or be avoided completely in high risk patients, such as chronic kidney disease (CKD) patients. Objective This study aimed to investigate the prescribing of NSAIDs in CKD patients in order to generate awareness and improve the outcome of these patients. Setting The study was conducted using medicine claims data in the private health sector of South Africa. Method A descriptive, quantitative study was performed, using retrospective data obtained from a Pharmaceutical Benefit Management company. Data from 1 January 2009 to 31 December 2013 were analysed. The study population consisted of all patients with an ICD-10 code for a CKD (N18), in association with a paid claim for an NSAID. Main outcome measure The stratification of NSAID prescribing volume among the CKD population in terms of gender, age, NSAID type, dosage and prescriber type. Results The prescribing of NSAIDs in CKD patients varied between 26 and 40 % over the 5 year study period. No association between gender and CKD patients who received NSAIDs versus those who did not was found, with p > 0.05 and Cramer's V < 0.1 for each year of the study. The association between age groups and CKD patients who received NSAIDs versus those who did not was statistically significant, but practically weak (p < 0.05; Cramer's V ≥ 0.1). Most NSAID prescriptions (52-63 %) were for patients aged 35-64 years. Diclofenac (34.25 %) was the single most frequently prescribed NSAID, but the COX-2-inhibitors (celecoxib, meloxicam and etoricoxib) were the preferred NSAID class to be prescribed. The majority (61.6 %) of the NSAIDs were prescribed by general medical practitioners in dosages meeting and even exceeding the recommended daily dosage of patients with normal kidney function. Conclusions Even though NSAIDs are

  6. PROX: Approximated Summarization of Data Provenance

    PubMed Central

    Ainy, Eleanor; Bourhis, Pierre; Davidson, Susan B.; Deutch, Daniel; Milo, Tova

    2016-01-01

    Many modern applications involve collecting large amounts of data from multiple sources, and then aggregating and manipulating it in intricate ways. The complexity of such applications, combined with the size of the collected data, makes it difficult to understand the application logic and how information was derived. Data provenance has been proven helpful in this respect in different contexts; however, maintaining and presenting the full and exact provenance may be infeasible, due to its size and complex structure. For that reason, we introduce the notion of approximated summarized provenance, where we seek a compact representation of the provenance at the possible cost of information loss. Based on this notion, we have developed PROX, a system for the management, presentation and use of data provenance for complex applications. We propose to demonstrate PROX in the context of a movies rating crowd-sourcing system, letting participants view provenance summarization and use it to gain insights on the application and its underlying data. PMID:27570843

  7. Inflammatory Bowel Disease.

    PubMed

    2016-01-01

    Inflammation response plays an important role in host survival, and it also leads to acute and chronic inflammatory diseases such as rheumatoid arthritis, bowel diseases, allergic rhinitis, asthma, atopic dermatitis and various neurodegenerative diseases. During the course of inflammation, the ROS level increases. In addition to ROS, several inflammatory mediators produced at the site lead to numerous cell-mediated damages. Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is a chronic intestinal disorder resulting from a dysfunctional epithelial, innate and adaptive immune response to intestinal microorganisms. The methods involving indomethacin-induced enterocolitis in rats with macroscopic changes of IBD, myeloperoxidase assay, microscopic (histologic) characters and biochemical parameters are discussed. PMID:26939275

  8. Tracking Provenance in ORNL's Flexible Research Platforms

    SciTech Connect

    Hensley, Zachary P; Sanyal, Jibonananda; New, Joshua Ryan

    2013-08-01

    Provenance is dened as information about the origin of objects, a concept that applies to both physical and digital objects and often overlaps both. The use of provenance in systems designed for research is an important but forgotten feature. Provenance allows for proper and exact tracking of information, its use, its lineage, its derivations and other metadata that are important for correctly adhering to the scien- tic method. In our project's prescribed use of provenance, researchers can determine detailed information about the use of sensor data in their experiments on ORNL's Flexible Research Platforms (FRPs). Our project's provenance system, Provenance Data Management System (ProvDMS), tracks information starting with the creation of information by an FRP sensor. The system determines station information, sensor information, and sensor channel information. The system allows researchers to derive generations of experiments from the sensor data and tracks their hierarchical flow. Key points can be seen in the history of the information as part of the information's workflow. The concept of provenance and its usage in science is relatively new and while used in other cases around the world, our project's provenance diers in a key area. To keep track of provenance, most systems must be designed or redesigned around the new provenance system. Our system is designed as a cohesive but sepa- rate entity and allows for researchers to continue using their own methods of analysis without being constrained in their ways in order to track the provenance. We have designed ProvDMS using a lightweight provenance library, Core Provenance Library (CPL) v.6 In addition to keeping track of sensor data experiments and its provenance, ProvDMS also provides a web-enabled visualization of the inheritance.

  9. Chronic pancreatitis.

    PubMed

    Majumder, Shounak; Chari, Suresh T

    2016-05-01

    Chronic pancreatitis describes a wide spectrum of fibro-inflammatory disorders of the exocrine pancreas that includes calcifying, obstructive, and steroid-responsive forms. Use of the term chronic pancreatitis without qualification generally refers to calcifying chronic pancreatitis. Epidemiology is poorly defined, but incidence worldwide seems to be on the rise. Smoking, drinking alcohol, and genetic predisposition are the major risk factors for chronic calcifying pancreatitis. In this Seminar, we discuss the clinical features, diagnosis, and management of chronic calcifying pancreatitis, focusing on pain management, the role of endoscopic and surgical intervention, and the use of pancreatic enzyme-replacement therapy. Management of patients is often challenging and necessitates a multidisciplinary approach. PMID:26948434

  10. Distinguishing Provenance Equivalence of Earth Science Data

    NASA Technical Reports Server (NTRS)

    Tilmes, Curt; Yesha, Ye; Halem, M.

    2010-01-01

    Reproducibility of scientific research relies on accurate and precise citation of data and the provenance of that data. Earth science data are often the result of applying complex data transformation and analysis workflows to vast quantities of data. Provenance information of data processing is used for a variety of purposes, including understanding the process and auditing as well as reproducibility. Certain provenance information is essential for producing scientifically equivalent data. Capturing and representing that provenance information and assigning identifiers suitable for precisely distinguishing data granules and datasets is needed for accurate comparisons. This paper discusses scientific equivalence and essential provenance for scientific reproducibility. We use the example of an operational earth science data processing system to illustrate the application of the technique of cascading digital signatures or hash chains to precisely identify sets of granules and as provenance equivalence identifiers to distinguish data made in an an equivalent manner.

  11. Chronic Trypanosoma cruzi infection potentiates adipose tissue macrophage polarization toward an anti-inflammatory M2 phenotype and contributes to diabetes progression in a diet-induced obesity model

    PubMed Central

    Cabalén, María E.; Cabral, María F.; Sanmarco, Liliana M.; Andrada, Marta C.; Onofrio, Luisina I.; Ponce, Nicolás E.; Aoki, María P.; Gea, Susana; Cano, Roxana C.

    2016-01-01

    Chronic obesity and Chagas disease (caused by the protozoan Trypanosoma cruzi) represent serious public health concerns. The interrelation between parasite infection, adipose tissue, immune system and metabolism in an obesogenic context, has not been entirely explored. A novel diet-induced obesity model (DIO) was developed in C57BL/6 wild type mice to examine the effect of chronic infection (DIO+I) on metabolic parameters and on obesity-related disorders. Dyslipidemia, hyperleptinemia, and cardiac/hepatic steatosis were strongly developed in DIO mice. Strikingly, although these metabolic alterations were collectively improved by infection, plasmatic apoB100 levels remain significantly increased in DIO+I, suggesting the presence of pro-atherogenic small and dense LDL particles. Moreover, acute insulin resistance followed by chronic hyperglycemia with hypoinsulinemia was found, evidencing an infection-related-diabetes progression. These lipid and glucose metabolic changes seemed to be highly dependent on TLR4 expression since TLR4−/− mice were protected from obesity and its complications. Notably, chronic infection promoted a strong increase in MCP-1 producing macrophages with a M2 (F4/80+CD11c-CD206+) phenotype associated to oxidative stress in visceral adipose tissue of DIO+I mice. Importantly, infection reduced lipid content but intensified inflammatory infiltrates in target tissues. Thus, parasite persistence in an obesogenic environment and the resulting host immunometabolic dysregulation may contribute to diabetes/atherosclerosis progression. PMID:26921251

  12. Special Issue: The First Provenance Challenge

    SciTech Connect

    Moreau, Luc; Ludaescher, Bertram T.; Altintas, Ilkay; Barga, Roger S.; Bowers, Shawn; Callahan, Steven P.; Chin, George; Clifford, Ben; Cohen, Shirley; Cohen-Boulakia, Sarah; Davidson, Susan; Deelman, Ewa; digiampietri, Luciano; Foster, Ian T.; Freire, Juliana; Frew, James; Futrelle, Joe; Gibson, Tara D.; Gil, Yolanda; Goble, Carole; Golbeck, Jennifer; Groth, Paul; Holland, David A.; Jiang, Sheng; Kim, Jihie; Koop, David; Krenek, Ales; McPhillips, Timothy; Mehta, Gaurang; Miles, Simon; Metzger, Dominic; Munroe, Steve; Myers, James D.; Plale, Beth A.; Podhorszki, norbert; Ratnakar, Varun; Emanuele , Santos; scheidegger, Carlos E.; Schuchardt, Karen L.; Seltzer, Margo I.; Simmhan, Yogesh L.; Claudio, Silva T.; Slaughter, Peter; Stephan, Eric G.; Stevens, Robert; Turi, Daniele; Vo, Huy T.; Wilde, Mike J.; Zhao, Jun; Zhao, Yong

    2008-04-01

    The first Provenance Challenge was set up in order to provide a forum for the community to help understand the capabilities of different provenance systems and the expressiveness of their provenance representations. To this end, a Functional Magnetic Resonance Imaging workflow was defined, which participants had to either simulate or run in order to produce some provenance representation, from which a set of identified queries had to be implemented and executed. Sixteen teams responded to the challenge, and submitted their inputs. In this paper, we present the challenge workflow and queries, and summarise the participants contributions.

  13. Intracellular Secretory Leukoprotease Inhibitor Modulates Inositol 1,4,5-Triphosphate Generation and Exerts an Anti-Inflammatory Effect on Neutrophils of Individuals with Cystic Fibrosis and Chronic Obstructive Pulmonary Disease

    PubMed Central

    Reeves, Emer P.; Banville, Nessa; Ryan, Dorothy M.; O'Reilly, Niamh; Bergin, David A.; Pohl, Kerstin; Molloy, Kevin; McElvaney, Oliver J.; Alsaleh, Khalifah; Aljorfi, Ahmed; Kandalaft, Osama; O'Flynn, Eimear; Geraghty, Patrick; O'Neill, Shane J.; McElvaney, Noel G.

    2013-01-01

    Secretory leukoprotease inhibitor (SLPI) is an anti-inflammatory protein present in respiratory secretions. Whilst epithelial cell SLPI is extensively studied, neutrophil associated SLPI is poorly characterised. Neutrophil function including chemotaxis and degranulation of proteolytic enzymes involves changes in cytosolic calcium (Ca2+) levels which is mediated by production of inositol 1,4,5-triphosphate (IP3) in response to G-protein-coupled receptor (GPCR) stimuli. The aim of this study was to investigate the intracellular function of SLPI and the mechanism-based modulation of neutrophil function by this antiprotease. Neutrophils were isolated from healthy controls (n = 10), individuals with cystic fibrosis (CF) (n = 5) or chronic obstructive pulmonary disease (COPD) (n = 5). Recombinant human SLPI significantly inhibited fMet-Leu-Phe (fMLP) and interleukin(IL)-8 induced neutrophil chemotaxis (P < 0.05) and decreased degranulation of matrix metalloprotease-9 (MMP-9), hCAP-18, and myeloperoxidase (MPO) (P < 0.05). The mechanism of inhibition involved modulation of cytosolic IP3 production and downstream Ca2+ flux. The described attenuation of Ca2+ flux was overcome by inclusion of exogenous IP3 in electropermeabilized cells. Inhibition of IP3 generation and Ca2+ flux by SLPI may represent a novel anti-inflammatory mechanism, thus strengthening the attractiveness of SLPI as a potential therapeutic molecule in inflammatory airway disease associated with excessive neutrophil influx including CF, non-CF bronchiectasis, and COPD. PMID:24073410

  14. Launch Services, a Proven Model

    NASA Astrophysics Data System (ADS)

    Trafton, W. C.; Simpson, J.

    2002-01-01

    From a commercial perspective, the ability to justify "leap frog" technology such as reusable systems has been difficult to justify because the estimated 5B to 10B investment is not supported in the current flat commercial market coupled with an oversupply of launch service suppliers. The market simply does not justify investment of that magnitude. Currently, next generation Expendable Launch Systems, including Boeing's Delta IV, Lockheed Martin's Atlas 5, Ariane V ESCA and RSC's H-IIA are being introduced into operations signifying that only upgrades to proven systems are planned to meet the changes in anticipated satellite demand (larger satellites, more lifetime, larger volumes, etc.) in the foreseeable future. We do not see a new fleet of ELVs emerging beyond that which is currently being introduced, only continuous upgrades of the fleet to meet the demands. To induce a radical change in the provision of launch services, a Multinational Government investment must be made and justified by World requirements. The commercial market alone cannot justify such an investment. And if an investment is made, we cannot afford to repeat previous mistakes by relying on one system such as shuttle for commercial deployment without having any back-up capability. Other issues that need to be considered are national science and security requirements, which to a large extent fuels the Japanese, Chinese, Indian, Former Soviet Union, European and United States space transportation entries. Additionally, this system must support or replace current Space Transportation Economies with across-the-board benefits. For the next 10 to 20 years, Multinational cooperation will be in the form of piecing together launch components and infrastructure to supplement existing launch systems and reducing the amount of non-recurring investment while meeting the future requirements of the End-User. Virtually all of the current systems have some form of multinational participation: Sea Launch

  15. Plasma Inflammatory Cytokine IL-4, IL-8, IL-10, and TNF-α Levels Correlate with Pulmonary Function in Patients with Asthma-Chronic Obstructive Pulmonary Disease (COPD) Overlap Syndrome

    PubMed Central

    Huang, Ai-Xia; Lu, Li-Wen; Liu, Wen-Juan; Huang, Mao

    2016-01-01

    Background The aim of this study was to investigate the plasma inflammatory cytokine levels and their correlations with pulmonary function in patients with asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS). Material/Methods Between January 2013 and December 2014, a total of 96 patients with asthma, acute exacerbation of chronic obstructive pulmonary disease (AECOPD), or ACOS were enrolled, and 35 healthy people were included as a control group. Fasting plasma interleukin (IL)-4, IL-8, IL-10, and tumor necrosis factor alpha (TNF-α) levels were detected using enzyme-linked immunosorbent assay (ELISA). Correlations between the plasma inflammatory cytokine levels and forced expiratory volume in 1 second (FEV1), FEV1/predicted value ratio (FEV1%pred), and FEV1/forced vital capacity (FVC) were analyzed. Results IL-4 and IL-8 levels showed statistically significant differences among the 3 groups of patients (both P<0.001); IL-4 level was significantly lower, while IL-8 level was significantly higher in the AECOPD group and ACOS group than those in the asthma group (all P<0.05). IL-10 level and TNF-α level were significantly different among the 3 patient groups (both P<0.001). IL-10 level was significantly different between each of the 2 groups (all P<0.001). TNF-α level in the asthma group was higher than in the AECOPD group and ACOS group (both P<0.001). IL-4 and IL-10 were positively and IL-8 and TNF-α were negatively related with FEV1, FEV1%pred, and FEV1/FVC. Conclusions Plasma levels of inflammatory cytokines IL-4, IL-8, IL-10, and TNF-α are related with severity of airway diseases and could be potential markers for the evaluation of asthma, COPD, and ACOS. PMID:27501772

  16. Why myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) may kill you: disorders in the inflammatory and oxidative and nitrosative stress (IO&NS) pathways may explain cardiovascular disorders in ME/CFS.

    PubMed

    Maes, Michael; Twisk, Frank Nm

    2009-01-01

    There is evidence that disorders in inflammatory and oxidative and nitrosative (IO&NS) pathways and a lowered antioxidant status are important pathophysiological mechanisms underpinning myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS). Important precipitating and perpetuating factors for ME/CFS are (amongst others) bacterial and viral infections; bacterial translocation due to an increased gut permeability; and psychological stress. Recently, Jason et al (2006) reported that the mean age of patients with myalgic encephalomyelitis/chronic fatigue syndrome dying from heart failure, i.e. 58.7 years, is significantly lower than the age of those dying from heart failure in the general US population, i.e. 83.1 years. These findings implicate that ME/CFS is a risk factor to cardio-vascular disorder. This review demonstrates that disorders in various IO&NS pathways provide explanations for the earlier mortality due to cardiovascular disorders in ME/CFS. These pathways are: a) chronic low grade inflammation with extended production of nuclear factor kappa B and COX-2 and increased levels of tumour necrosis factor alpha; b) increased O&NS with increased peroxide levels, and phospholipid oxidation including oxidative damage to phosphatidylinositol; c) decreased levels of specific antioxidants, i.e. coenzyme Q10, zinc and dehydroepiandrosterone-sulphate; d) bacterial translocation as a result of leaky gut; e) decreased omega-3 polyunsatutared fatty acids (PUFAs), and increased omega-6 PUFA and saturated fatty acid levels; and f) the presence of viral and bacterial infections and psychological stressors. The mechanisms whereby each of these factors may contribute towards cardio-vascular disorder in ME/CFS are discussed. ME/CFS is a multisystemic metabolic-inflammatory disorder. The aberrations in IO&NS pathways may increase the risk for cardiovascular disorders. PMID:20038921

  17. Provenance for Earth Science Data Systems

    NASA Astrophysics Data System (ADS)

    Hua, H.; Tilmes, C.; Ramapriyan, H. K.; Duggan, B.; Wilson, B. D.; Manipon, G. J. M.

    2014-12-01

    Earth Science Data Systems across NASA play a critical role in data processing, management, and analysis of NASA observations. However, there is a growing need to provide the provenance of these datasets as scientists increasingly need more transparency of the data products to improve their understanding and trust of the science results. Lessons learned from Climategate show that there is public demand for more transparency and understanding in the science process. Science data systems are key to enabling the capture, management, and use of production provenance information. Science analysis now also may involve merging multi-sensor datasets where lineage can facilitate the understanding of the data. But there does not exist a formal recommendation for an interoperable standard for provenance representation for use in NASA's Earth Science Data Systems. The W3C Provenance Working Group has a specification for the representation of provenance information. The standard is very general and intended to support the breadth of any domain. To better serve the needs of specific domain communities, the standard has several built in points of extensibility. We will present efforts by NASA's Earth Science Data Systems Working Group (ESDSWG) on Provenance to develop an Earth Science extension to the PROV specification (PROV-ES) and how it can be used in science data system to capture, consume, and interpret provenance information.

  18. High content cell-based assay for the inflammatory pathway

    NASA Astrophysics Data System (ADS)

    Mukherjee, Abhishek; Song, Joon Myong

    2015-07-01

    Cellular inflammation is a non-specific immune response to tissue injury that takes place via cytokine network orchestration to maintain normal tissue homeostasis. However chronic inflammation that lasts for a longer period, plays the key role in human diseases like neurodegenerative disorders and cancer development. Understanding the cellular and molecular mechanisms underlying the inflammatory pathways may be effective in targeting and modulating their outcome. Tumor necrosis factor alpha (TNF-α) is a pro-inflammatory cytokine that effectively combines the pro-inflammatory features with the pro-apoptotic potential. Increased levels of TNF-α observed during acute and chronic inflammatory conditions are believed to induce adverse phenotypes like glucose intolerance and abnormal lipid profile. Natural products e. g., amygdalin, cinnamic acid, jasmonic acid and aspirin have proven efficacy in minimizing the TNF-α induced inflammation in vitro and in vivo. Cell lysis-free quantum dot (QDot) imaging is an emerging technique to identify the cellular mediators of a signaling cascade with a single assay in one run. In comparison to organic fluorophores, the inorganic QDots are bright, resistant to photobleaching and possess tunable optical properties that make them suitable for long term and multicolor imaging of various components in a cellular crosstalk. Hence we tested some components of the mitogen activated protein kinase (MAPK) pathway during TNF-α induced inflammation and the effects of aspirin in HepG2 cells by QDot multicolor imaging technique. Results demonstrated that aspirin showed significant protective effects against TNF-α induced cellular inflammation. The developed cell based assay paves the platform for the analysis of cellular components in a smooth and reliable way.

  19. Subcutaneous immunoglobulin therapy for inflammatory neuropathy: current evidence base and future prospects.

    PubMed

    Rajabally, Yusuf A

    2014-06-01

    Intravenous immunoglobulin therapy is of proven effect in chronic inflammatory neuropathies, including chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN). In more recent years, there have been a number of anecdotal case reports and small series, followed by a few trials of variable design, of subcutaneous immunoglobulin therapy in these neuropathies. To date, limited evidence suggests that the subcutaneous route may be a more clinically effective, better-tolerated, at least cost-equivalent and a more patient-friendly option than the still more used intravenous alternative. Long-term efficacy is not as yet established in neuropathic indications by randomised controlled clinical trial evidence, and it is likely that the subcutaneous route may not be suitable in all cases with some hints to this effect appearing from the limited data available to date. Further studies are ongoing, including those of dose comparison, and more are likely to be planned in future. The literature on the use of subcutaneous immunoglobulin therapy in chronic inflammatory neuropathy is reviewed here. The current use in clinical practice, day-to-day benefits, including quality of life measures and health economics as published thus far, are evaluated. The limitations of this form of treatment in CIDP and MMN are also analysed in the light of current literature and taking into account the remaining unknowns. Future prospects and research with this mode of immunoglobulin therapy administration are discussed. PMID:24124042

  20. Anti-inflammatory effects of a polyphenols-rich extract from tea (Camellia sinensis) flowers in acute and chronic mice models.

    PubMed

    Chen, Bang-Tian; Li, Wei-Xi; He, Rong-Rong; Li, Yi-Fang; Tsoi, Bun; Zhai, Yu-Jia; Kurihara, Hiroshi

    2012-01-01

    While beneficial health properties of tea leaves have been extensively studied, less attention is paid to the flowers of tea. In this study, the anti-inflammatory effects of hot water extract of tea (Camellia sinensis) flowers were investigated. Pharmacological studies found that administration of tea flowers extract (TFE) could effectively inhibit croton oil-induced ear edema and carrageenin-induced paw edema. Furthermore, administration of TFE also protected against Propionibacterium acnes (P. ances) plus lipopolysaccharide-(LPS-) induced liver inflammation by reversing the histologic damage and plasma alanine aminotransferase (ALT) increase. Moreover, the levels of nitric oxide (NO), tumor necrosis factor-(TNF)-α and interleukin-(IL-) 1β mRNA in mouse liver were markedly suppressed after treatment with TFE in mice with immunological liver inflammation. These results indicated that tea flowers had potent anti-inflammatory effects on acute and immunological inflammation in vivo, and may be used as a functional natural food. PMID:22900128

  1. The expression of inflammatory cytokines, TAM tyrosine kinase receptors and their ligands is upregulated in venous leg ulcer patients: a novel insight into chronic wound immunity.

    PubMed

    Filkor, Kata; Németh, Tibor; Nagy, István; Kondorosi, Éva; Urbán, Edit; Kemény, Lajos; Szolnoky, Győző

    2016-08-01

    The systemic host defence mechanisms, especially innate immunity, in venous leg ulcer patients are poorly investigated. The aim of the current study was to measure Candida albicans killing activity and gene expressions of pro- and anti-inflammatory cytokines and innate immune response regulators, TAM receptors and ligands of peripheral blood mononuclear cells separated from 69 venous leg ulcer patients and 42 control probands. Leg ulcer patients were stratified into responder and non-responder groups on the basis of wound healing properties. No statistical differences were found in Candida killing among controls, responders and non-responders. Circulating blood mononuclear cells of patients overexpress pro-inflammatory (IL-1α, TNFα, CXCL-8) and anti-inflammatory (IL-10) cytokines as well as TAM receptors (Tyro, Axl, MerTK) and their ligands Gas6 and Protein S compared with those of control individuals. IL-1α is notably overexpressed in venous leg ulcer treatment non-responders; in contrast, Axl gene expression is robustly stronger among responders. These markers may be considered as candidates for the prediction of treatment response among venous leg ulcer patients. PMID:26192232

  2. Should obesity be the main game? Or do we need an environmental makeover to combat the inflammatory and chronic disease epidemics?

    PubMed

    Egger, G; Dixon, J

    2009-03-01

    There is a link between obesity and chronic disease. However, the causal relationship is complicated. Some forms of obesity are associated with low-level systemic inflammation, which is linked to disease. But lifestyle behaviours that may not necessarily cause obesity (poor diet, inadequate sleep, smoking, etc.) can independently cause inflammation and consequent disease. It is proposed here that it is the environment driving modern lifestyles, which is the true cause of much chronic disease, rather than obesity per se, and that obesity may be a marker of environmental derangement, rather than the primary cause of the problem. Attempts to clinically manage obesity alone on a large scale are therefore unlikely to be successful at the population level without significant lifestyle or environmental change. Environmental factors influencing obesity and health have now also been implicated in ecological perturbations such as climate change, through the shift to positive energy balance in humans caused by the exponential use of fossil fuels in such areas as transport, and consequent rises in carbon emissions into the atmosphere. It is proposed therefore that a more policy-based approach to dealing with obesity, which attacks the common causes of both biological and ecological 'dis-ease', could have positive effects on both chronic disease and environmental problems. A plea is thus made for a greater health input into discussions on environmental regulation for chronic disease control, as well as climate change. PMID:19055538

  3. Tracking Provenance of Earth Science Data

    NASA Technical Reports Server (NTRS)

    Tilmes, Curt; Yesha, Yelena; Halem, Milton

    2010-01-01

    Tremendous volumes of data have been captured, archived and analyzed. Sensors, algorithms and processing systems for transforming and analyzing the data are evolving over time. Web Portals and Services can create transient data sets on-demand. Data are transferred from organization to organization with additional transformations at every stage. Provenance in this context refers to the source of data and a record of the process that led to its current state. It encompasses the documentation of a variety of artifacts related to particular data. Provenance is important for understanding and using scientific datasets, and critical for independent confirmation of scientific results. Managing provenance throughout scientific data processing has gained interest lately and there are a variety of approaches. Large scale scientific datasets consisting of thousands to millions of individual data files and processes offer particular challenges. This paper uses the analogy of art history provenance to explore some of the concerns of applying provenance tracking to earth science data. It also illustrates some of the provenance issues with examples drawn from the Ozone Monitoring Instrument (OMI) Data Processing System (OMIDAPS) run at NASA's Goddard Space Flight Center by the first author.

  4. Anti-inflammatory properties of the monoterpene 1.8-cineole: current evidence for co-medication in inflammatory airway diseases.

    PubMed

    Juergens, U R

    2014-12-01

    1,8-cineole is a natural monoterpene, also known as eucalyptol. It is a major compound of many plant essential oils, mainly extracted from Eucalyptus globulus oil. As an isolated compound, 1,8-cineole is known for its mucolytic and spasmolytic action on the respiratory tract, with proven clinical efficacy. 1,8-cineole has also shown therapeutic benefits in inflammatory airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD). This clinical evidence refers to its anti-inflammatory and anti-oxidant mode of action, which has been proven in numerous pre-clinical studies. In vitro studies found strong evidence that 1,8-cineole controls inflammatory processes and mediator production of infection- or inflammation-induced mucus hypersecretion by its action as anti-inflammatory modifier rather than a simple mucolytic agent. The aim of this review is to present these preclinical studies performed with the pure monoterpene, and to summarize the current knowledge on the mode of action of 1,8-cineole. The actual understanding of the pure 1,8-cineole compared to mixtures of natural volatile oils containing 1,8-cineole as a major compound and to mixtures of natural terpenes, known as essential oils, will be discussed. Based on the anti-oxidative and anti-inflammatory properties, recent clinical trials with 1,8-cineole have shown first evidence for the beneficial use of 1,8-cineole as long-term therapy in the prevention of COPD-exacerbations and to improve asthma control. PMID:24831245

  5. Idiopathic Inflammatory Myopathies

    PubMed Central

    Dimachkie, Mazen M.; Barohn, Richard J.

    2012-01-01

    The idiopathic inflammatory myopathies are a group of rare disorders including polymyositis (PM), dermatomyositis (DM), and autoimmune necrotizing myopathies (NMs). The idiopathic inflammatory myopathies share many similarities. They present acutely, subacutely, or chronically with marked proximal and symmetric muscle weakness, except for associated distal and asymmetric weakness in inclusion body myositis. The idiopathic inflammatory myopathies also share a variable degree of creatine kinase (CK) elevation and a nonspecifically abnormal electromyogram demonstrating an irritative myopathy. The muscle pathology demonstrates inflammatory exudates of variable distribution within the muscle fascicle. Despite these similarities, the idiopathic inflammatory myopathies are a heterogeneous group. The overlap syndrome (OS) refers to the association of PM, DM, or NM with connective tissue disease, such as scleroderma or systemic lupus erythematosus. In addition to elevated antinuclear antibodies (ANA), patients with OS may be weaker in the proximal arms than the legs mimicking the pattern seen in some muscular dystrophies. In this review, we focus on DM, PM, and NM and examine current and promising therapies. PMID:23117947

  6. A novel substituted aminoquinoline selectively targets voltage-sensitive sodium channel isoforms and NMDA receptor subtypes and alleviates chronic inflammatory and neuropathic pain.

    PubMed

    Tabakoff, Boris; Ren, Wenhua; Vanderlinden, Lauren; Snell, Lawrence D; Matheson, Christopher J; Wang, Ze-Jun; Levinson, Rock; Smothers, C Thetford; Woodward, John J; Honse, Yumiko; Lovinger, David; Rush, Anthony M; Sather, William A; Gustafson, Daniel L; Hoffman, Paula L

    2016-08-01

    Recent understanding of the systems that mediate complex disease states, has generated a search for molecules that simultaneously modulate more than one component of a pathologic pathway. Chronic pain syndromes are etiologically connected to functional changes (sensitization) in both peripheral sensory neurons and in the central nervous system (CNS). These functional changes involve modifications of a significant number of components of signal generating, signal transducing and signal propagating pathways. Our analysis of disease-related changes which take place in sensory neurons during sensitization led to the design of a molecule that would simultaneously inhibit peripheral NMDA receptors and voltage sensitive sodium channels. In the current report, we detail the selectivity of N,N-(diphenyl)-4-ureido-5,7-dichloro-2-carboxy-quinoline (DCUKA) for action at NMDA receptors composed of different subunit combinations and voltage sensitive sodium channels having different α subunits. We show that DCUKA is restricted to the periphery after oral administration, and that circulating blood levels are compatible with its necessary concentrations for effects at the peripheral cognate receptors/channels that were assayed in vitro. Our results demonstrate that DCUKA, at concentrations circulating in the blood after oral administration, can modulate systems which are upregulated during peripheral sensitization, and are important for generating and conducting pain information to the CNS. Furthermore, we demonstrate that DCUKA ameliorates the hyperalgesia of chronic pain without affecting normal pain responses in neuropathic and inflammation-induced chronic pain models. PMID:27158117

  7. Chronic Psychological Stress as a Risk Factor of Osteoporosis.

    PubMed

    Azuma, Kagaku; Adachi, Yasuhiro; Hayashi, Haruki; Kubo, Kin-Ya

    2015-12-01

    Osteoporosis, the most common metabolic skeletal disease, is characterized by decreased bone mass and deteriorated bone quality, leading to increased fracture risk. With the aging of the population, osteoporotic fracture is an important public health issue. Organisms are constantly exposed to various stressful stimuli that affect physiological processes. Recent studies showed that chronic psychological stress is a risk factor for osteoporosis by various signaling pathways. The purpose of this article is to review the recent progress of the association between chronic psychological stress and osteoporosis. Increasing evidence confirms the physiological importance of the central nervous system, especially the hypothalamus, in the regulation of bone metabolism. Both animal and human studies indicate that chronic psychological stress induces a decrease of bone mass and deterioration of bone quality by influencing the hypothalamic-pituitary-adrenocortical (HPA) axis, sympathetic nervous system, and other endocrine, immune factors. Active mastication, proven to be an effective stress-coping behavior, can attenuate stress-induced neuroendocrine responses and ameliorate stress-induced bone loss. Therefore, active mastication may represent a useful approach in preventing and/or treating chronic stress-associated osteoporosis. We also discuss several potential mechanisms involved in the interaction between chronic stress, mastication and osteoporosis. Chronic stress activates the HPA axis and sympathetic nervous system, suppresses the secretion of gonadal hormone and growth hormone, and increases inflammatory cytokines, eventually leading to bone loss by inhibiting bone formation and stimulating bone resorption. PMID:26667192

  8. Provenance in Observational Solar Physics Data Pipelines

    NASA Astrophysics Data System (ADS)

    McGuinness, D.; Fox, P.; Garcia, J.; Zednik, S.

    2008-05-01

    A limiting factor for virtual observatories which intend to make diverse data sets available to a diverse user base is that the following use cases are very difficult to implement: 1. Determine which flat field calibration was applied to the image taken on January, 26, 2005 around 2100UT by the ACOS Mark IV polarimeter. 2. What processing steps were completed to obtain the ACOS PICS limb image of the day for January 26, 2005. 3. What was the cloud cover and atmospheric seeing conditions during the local morning of January 26, 2005 at MLSO. Key to addressing these use cases often requires information that was either not collected from different stages in the data processing pipeline or it was but was not carried forward when the datasets were made available on-line. Collectively, this information is called provenance and in a semantic web data framework; knowledge provenance. In this presentation, we describe the knowledge provenance requirements that have emerged in our previous work on virtual observatories as well as requirements identified from a series of uses cases collected from scientific data users and instrument scientists. We will describe the progress we are making on meeting these requirements in the context of solar physics image data processing pipelines. The Semantic Provenance Capture in Data Ingest Systems (SPCDIS) is a NSF OCI/SDCI-funded project to implement an extensible meta data provenance scheme within the Virtual Solar-Terrestrial Observatory.

  9. An R package for statistical provenance analysis

    NASA Astrophysics Data System (ADS)

    Vermeesch, Pieter; Resentini, Alberto; Garzanti, Eduardo

    2016-05-01

    This paper introduces provenance, a software package within the statistical programming environment R, which aims to facilitate the visualisation and interpretation of large amounts of sedimentary provenance data, including mineralogical, petrographic, chemical and isotopic provenance proxies, or any combination of these. provenance comprises functions to: (a) calculate the sample size required to achieve a given detection limit; (b) plot distributional data such as detrital zircon U-Pb age spectra as Cumulative Age Distributions (CADs) or adaptive Kernel Density Estimates (KDEs); (c) plot compositional data as pie charts or ternary diagrams; (d) correct the effects of hydraulic sorting on sandstone petrography and heavy mineral composition; (e) assess the settling equivalence of detrital minerals and grain-size dependence of sediment composition; (f) quantify the dissimilarity between distributional data using the Kolmogorov-Smirnov and Sircombe-Hazelton distances, or between compositional data using the Aitchison and Bray-Curtis distances; (e) interpret multi-sample datasets by means of (classical and nonmetric) Multidimensional Scaling (MDS) and Principal Component Analysis (PCA); and (f) simplify the interpretation of multi-method datasets by means of Generalised Procrustes Analysis (GPA) and 3-way MDS. All these tools can be accessed through an intuitive query-based user interface, which does not require knowledge of the R programming language. provenance is free software released under the GPL-2 licence and will be further expanded based on user feedback.

  10. Effects of Standardised Fermented Papaya Gel on Clinical Symptoms, Inflammatory Cytokines, and Nitric Oxide Metabolites in Patients with Chronic Periodontitis: An Open Randomised Clinical Study.

    PubMed

    Kharaeva, Zaira F; Zhanimova, Lyana R; Mustafaev, Magomet Sh; De Luca, Chiara; Mayer, Wolfgang; Chung Sheun Thai, Jeffrey; Tiew Siok Tuan, Rebecca; Korkina, Liudmila G

    2016-01-01

    The clinical efficacy of topical administration of standardised fermented papaya gel (SFPG), known to have antioxidant and anti-inflammatory properties, versus conventional therapy was evaluated in a group of 84 patients with moderate-to-severe periodontitis, randomly assigned to control group (n = 45) undergoing traditional pharmacologic/surgical protocols or to experimental group (n = 39), additionally treated with intragingival pocket SFPG (7 g) applications (15 min daily for 10 days). Patients undergoing SFPG treatment showed significant (P < 0.05), durable improvement of three major clinical indices of disease severity: reduced bleeding (day 7), plaque and gingival conditions (day 14), and consistent gingival pocket depth reduction (day 45). Proinflammatory nitric oxide metabolites reached normal values in plasma (day 14) and gingival crevicular fluid (GCF) at day 45 with SFPG applications compared to controls that did not reach normalisation. Levels of highly increased proinflammatory (IL-1B, IL-6) and suppressed anti-inflammatory (IL-10) cytokines normalised in the SFPG group by days 14 (plasma) and 45 (GCF), but never in the control group. Although not acting directly as antibiotic, SFPG acted in synergy with human granulocytes blocking adaptive catalase induction in S. aureus in response to granulocyte-derived oxidative stress, thus enhancing intracellular bacterial killing. PMID:26977121

  11. Effects of Standardised Fermented Papaya Gel on Clinical Symptoms, Inflammatory Cytokines, and Nitric Oxide Metabolites in Patients with Chronic Periodontitis: An Open Randomised Clinical Study

    PubMed Central

    Kharaeva, Zaira F.; Zhanimova, Lyana R.; Mustafaev, Magomet Sh.; De Luca, Chiara; Mayer, Wolfgang; Chung Sheun Thai, Jeffrey; Tiew Siok Tuan, Rebecca; Korkina, Liudmila G.

    2016-01-01

    The clinical efficacy of topical administration of standardised fermented papaya gel (SFPG), known to have antioxidant and anti-inflammatory properties, versus conventional therapy was evaluated in a group of 84 patients with moderate-to-severe periodontitis, randomly assigned to control group (n = 45) undergoing traditional pharmacologic/surgical protocols or to experimental group (n = 39), additionally treated with intragingival pocket SFPG (7 g) applications (15 min daily for 10 days). Patients undergoing SFPG treatment showed significant (P < 0.05), durable improvement of three major clinical indices of disease severity: reduced bleeding (day 7), plaque and gingival conditions (day 14), and consistent gingival pocket depth reduction (day 45). Proinflammatory nitric oxide metabolites reached normal values in plasma (day 14) and gingival crevicular fluid (GCF) at day 45 with SFPG applications compared to controls that did not reach normalisation. Levels of highly increased proinflammatory (IL-1B, IL-6) and suppressed anti-inflammatory (IL-10) cytokines normalised in the SFPG group by days 14 (plasma) and 45 (GCF), but never in the control group. Although not acting directly as antibiotic, SFPG acted in synergy with human granulocytes blocking adaptive catalase induction in S. aureus in response to granulocyte-derived oxidative stress, thus enhancing intracellular bacterial killing. PMID:26977121

  12. Inflammatory Bowel “Cardiac” Disease: Point Prevalence of Atrial Fibrillation in Inflammatory Bowel Disease Population

    PubMed Central

    Pattanshetty, Deepak J.; Anna, Kiran; Gajulapalli, Rama D.; Sappati-Biyyani, RajaShekhar R.

    2015-01-01

    Background/Aim: Proinflammatory markers such as interleukin (IL)-6 have been closely associated with atrial fibrillation (AF). These markers are characteristically elevated in chronic inflammatory bowel disease (IBD) and positively correlate with disease activity. Although IBD and AF have similar pathogenesis, there have been very limited studies looking at their association. The aim of this study is to determine the prevalence of AF in patients with IBD. Patients and Methods: Medical records of patients with biopsy proven IBD (n = 203, both in and outpatient) were retrospectively reviewed. One hundred and forty-one IBD patients with documentary evidence of electrocardiograms (ECG's) were included. The “Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA)” study, a large cross-sectional study (n = 1.89 million) done to evaluate the prevalence of AF among the US population, was our control population. All ECGs available till December 2010 for each IBD patient were reviewed carefully for evidence of AF. We studied the prevalence of AF among IBD population and compared it to that of control (ATRIA) population. Results: The prevalence of AF was significantly higher among IBD patients compared with the ATRIA study patients (11.3% vs 0.9%, P < 0.0001). Additionally, the IBD patient population were much younger compared with the controls (64.4 ± 10.7 vs 71.2 ± 12.2, P = 0.02). Conclusion: AF has an overall higher prevalence across all age groups in IBD compared with the subjects of ATRIA study, which could be due to the chronic inflammatory state of IBD. Further studies are needed to study the association in detail. PMID:26458861

  13. Sediment generation and provenance: processes and pathways

    NASA Astrophysics Data System (ADS)

    Caracciolo, L.; Garzanti, E.; von Eynatten, H.; Weltje, G. J.

    2016-05-01

    The ability to trace sediments from their sources to sedimentary basins is a prerequisite for quantitative analysis of Earth-surface dynamics. The comparatively recent revival of sedimentary provenance analysis goes hand-in-hand with the ever expanding range of analytical tools available for quantifying sediment properties (isotopic, mineral, chemical, and petrographic composition, grain-size and shape distributions, age spectra, etc.), and for interpreting such data in paleo-geographic, -tectonic and -climatic terms. The breakdown of sediment budgets into source-specific contributions - one of the most important tasks of provenance analysis - permits quantification of rates of surface processes in the geological past ("deep time"), even in cases where the source areas themselves have been destroyed by global tectonics. Quantitative sedimentary provenance analysis is therefore crucial to the reconstruction of ancient sediment-routing systems, the fundamental units of mass transfer at the Earth's surface.

  14. Analysis Traceability and Provenance for HEP

    NASA Astrophysics Data System (ADS)

    Shamdasani, Jetendr; McClatchey, Richard; Branson, Andrew; Kovács, Zsolt

    2015-12-01

    This paper presents the use of the CRISTAL software in the N4U project. CRISTAL was used to create a set of provenance aware analysis tools for the Neuroscience domain. This paper advocates that the approach taken in N4U to build the analysis suite is sufficiently generic to be able to be applied to the HEP domain. A mapping to the PROV model for provenance interoperability is also presented and how this can be applied to the HEP domain for the interoperability of HEP analyses.

  15. Plant Derived Aporphinic Alkaloid S-(+)-Dicentrine Induces Antinociceptive Effect in Both Acute and Chronic Inflammatory Pain Models: Evidence for a Role of TRPA1 Channels

    PubMed Central

    Montrucchio, Deise Prehs; Córdova, Marina Machado; Soares Santos, Adair Roberto

    2013-01-01

    S-(+)-Dicentrine is an aporphinic alkaloid found in several plant species, mainly from Lauraceae family, which showed significant antinociceptive activity in an acute model of visceral pain in mice. In this work, we extended the knowledge on the antinociceptive properties of S-(+)-dicentrine and showed that this alkaloid also attenuates mechanical and cold hypersensitivity associated with cutaneous inflammation induced by Complete Freund’s Adjuvant in mice. Given orally, S-(+)-dicentrine (100 mg/kg) reversed CFA-induced mechanical hypersensitivity, evaluated as the paw withdrawal threshold to von Frey hairs, and this effect lasted up to 2 hours. S-(+)-Dicentrine also reversed CFA-induced cold hypersensitivity, assessed as the responses to a drop of acetone in the injured paw, but did not reverse the heat hypersensitivity, evaluated as the latency time to paw withdrawal in the hot plate (50°C). Moreover, S-(+)-dicentrine (100 mg/kg, p.o.) was effective in inhibit nociceptive responses to intraplantar injections of cinnamaldehyde, a TRPA1 activator, but not the responses induced by capsaicin, a TRPV1 activator. When administered either by oral or intraplantar routes, S-(+)-dicentrine reduced the licking time (spontaneous nociception) and increased the latency time to paw withdrawal in the cold plate (cold hypersensitivity), both induced by the intraplantar injection of cinnamaldehyde. Taken together, our data adds information about antinociceptive properties of S-(+)-dicentrine in inflammatory conditions, reducing spontaneous nociception and attenuating mechanical and cold hypersensitivity, probably via a TRPA1-dependent mechanism. It also indicates that S-(+)-dicentrine might be potentially interesting in the development of new clinically relevant drugs for the management of persistent pain, especially under inflammatory conditions. PMID:23861794

  16. Keratoconus: an inflammatory disorder?

    PubMed Central

    Galvis, V; Sherwin, T; Tello, A; Merayo, J; Barrera, R; Acera, A

    2015-01-01

    Keratoconus has been classically defined as a progressive, non-inflammatory condition, which produces a thinning and steepening of the cornea. Its pathophysiological mechanisms have been investigated for a long time. Both genetic and environmental factors have been associated with the disease. Recent studies have shown a significant role of proteolytic enzymes, cytokines, and free radicals; therefore, although keratoconus does not meet all the classic criteria for an inflammatory disease, the lack of inflammation has been questioned. The majority of studies in the tears of patients with keratoconus have found increased levels of interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α), and matrix metalloproteinase (MMP)-9. Eye rubbing, a proven risk factor for keratoconus, has been also shown recently to increase the tear levels of MMP-13, IL-6, and TNF-α. In the tear fluid of patients with ocular rosacea, IL-1α and MMP-9 have been reported to be significantly elevated, and cases of inferior corneal thinning, resembling keratoconus, have been reported. We performed a literature review of published biochemical changes in keratoconus that would support that this could be, at least in part, an inflammatory condition. PMID:25931166

  17. Keratoconus: an inflammatory disorder?

    PubMed

    Galvis, V; Sherwin, T; Tello, A; Merayo, J; Barrera, R; Acera, A

    2015-07-01

    Keratoconus has been classically defined as a progressive, non-inflammatory condition, which produces a thinning and steepening of the cornea. Its pathophysiological mechanisms have been investigated for a long time. Both genetic and environmental factors have been associated with the disease. Recent studies have shown a significant role of proteolytic enzymes, cytokines, and free radicals; therefore, although keratoconus does not meet all the classic criteria for an inflammatory disease, the lack of inflammation has been questioned. The majority of studies in the tears of patients with keratoconus have found increased levels of interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α), and matrix metalloproteinase (MMP)-9. Eye rubbing, a proven risk factor for keratoconus, has been also shown recently to increase the tear levels of MMP-13, IL-6, and TNF-α. In the tear fluid of patients with ocular rosacea, IL-1α and MMP-9 have been reported to be significantly elevated, and cases of inferior corneal thinning, resembling keratoconus, have been reported. We performed a literature review of published biochemical changes in keratoconus that would support that this could be, at least in part, an inflammatory condition. PMID:25931166

  18. Applying Content Management to Automated Provenance Capture

    SciTech Connect

    Schuchardt, Karen L.; Gibson, Tara D.; Stephan, Eric G.; Chin, George

    2008-04-10

    Workflows and data pipelines are becoming increasingly valuable in both computational and experimen-tal sciences. These automated systems are capable of generating significantly more data within the same amount of time than their manual counterparts. Automatically capturing and recording data prove-nance and annotation as part of these workflows is critical for data management, verification, and dis-semination. Our goal in addressing the provenance challenge was to develop and end-to-end system that demonstrates real-time capture, persistent content management, and ad-hoc searches of both provenance and metadata using open source software and standard protocols. We describe our prototype, which extends the Kepler workflow tools for the execution environment, the Scientific Annotation Middleware (SAM) content management software for data services, and an existing HTTP-based query protocol. Our implementation offers several unique capabilities, and through the use of standards, is able to pro-vide access to the provenance record to a variety of commonly available client tools.

  19. Chronic restraint stress induces mechanical and cold allodynia, and enhances inflammatory pain in rat: Relevance to human stress-associated painful pathologies.

    PubMed

    Bardin, L; Malfetes, N; Newman-Tancredi, A; Depoortère, R

    2009-12-28

    Whereas acute stress often results in analgesia, chronic stress can trigger hyperalgesia/allodynia. This influence of long-term stress on nociception is relevant to numerous painful pathologies, such as fibromyalgia (FM), characterized by diffuse muscular pain (hyperalgesia) and/or tenderness (allodynia). Hence, there is a need for pre-clinical models integrating a chronic-stress dimension to the study of pain. Here, we assessed the effects of protracted/intermittent stress produced by daily, 1h restraint periods in cylinders, 4 days/week over 5 weeks, on eight models of hyperalgesia and allodynia in rats. This type of stress potentiated chemical hyperalgesia in the formalin model (160 and 76% increase of pain score above controls, during the early and late phases, respectively). It also produced thermal allodynia in response to cold (paw acetone test: 200% increase of allodynia score during week 3-5) and heat (42 degrees C tail immersion test: 15% decrease of withdrawal threshold, from week 2 onward). This stress also resulted in mechanical allodynia in the von Frey filaments model (60% decrease in threshold during week 2-5). However, such a stress regimen had no influence in the Randall-Selitto test of mechanical hyperalgesia, and in the tail immersion models of cold (4 degrees C) or hot (48 degrees C) thermal hyperalgesia, as well as cold (15 degrees C) allodynia. This model of prolonged/intermittent restraint stress may be useful in investigating the mechanisms linking stress and pain, and provide an assay to assess the potential therapeutic efficacy of drugs targeted against painful pathologies with a strong stress component, including but not restricted to FM. PMID:19616033

  20. Microbiota biodiversity in inflammatory bowel disease

    PubMed Central

    2014-01-01

    Gut microbiota plays a significant role in human health and energy balance, and provides protection against disease states. An altered balance between microbiota and its host (dysbiosis) would appear to contribute to the development of Inflammatory Bowel Disease (IBD), Crohn’s Disease (CD) and Ulcerative Colitis (UC). CD and UC are chronic inflammatory diseases of the gastrointestinal tes. PMID:24684926

  1. Recent Advances on the Possible Neuroprotective Activities of Epstein-Barr Virus Oncogene BARF1 Protein in Chronic Inflammatory Disorders of Central Nervous System

    PubMed Central

    Wynne, Alicia; Kanwar, Rupinder K; Khanna, Rajiv; Kanwar, Jagat R

    2010-01-01

    Multiple sclerosis and neurodegenerative diseases in which cells of the central nervous system (CNS) are lost or damaged are rapidly increasing in frequency, and there is neither effective treatment nor cure to impede or arrest their destructive course. The Epstein-Barr virus is a human gamma-herpesvirus that infects more than 90% of the human population worldwide and persisting for the lifetime of the host. It is associated with numerous epithelial cancers, principally undifferentiated nasopharyngeal carcinoma and gastric carcinoma. Individuals with a history of symptomatic primary EBV infection, called infectious mononucleosis, carry a moderately higher risk of developing multiple sclerosis (MS). It is not known how EBV infection potentially promotes autoimmunity and central nervous system (CNS) tissue damage in MS. Recently it has been found that EBV isolates from different geographic regions have highly conserved BARF1 epitopes. BARF1 protein has the neuroprotective and mitogenic activity, thus may be useful to combat and overcome neurodegenerative disease. BARF1 protein therapy can potentially be used to enhance the neuroprotective activities by combinational treatment with anti-inflammatory antagonists and neuroprotectors in neural disorders. PMID:21358976

  2. Inflammatory and oncogenic roles of a tumor stem cell marker doublecortin-like kinase (DCLK1) in virus-induced chronic liver diseases.

    PubMed

    Ali, Naushad; Chandrakesan, Parthasarathy; Nguyen, Charles B; Husain, Sanam; Gillaspy, Allison F; Huycke, Mark; Berry, William L; May, Randal; Qu, Dongfeng; Weygant, Nathaniel; Sureban, Sripathi M; Bronze, Michael S; Dhanasekaran, Danny N; Houchen, Courtney W

    2015-08-21

    Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related mortality worldwide. We previously showed that a tumor/cancer stem cell (CSC) marker, doublecortin-like kinase (DCLK1) positively regulates hepatitis C virus (HCV) replication, and promotes tumor growth in colon and pancreas. Here, we employed transcriptome analysis, RNA interference, tumor xenografts, patient's liver tissues and hepatospheroids to investigate DCLK1-regulated inflammation and tumorigenesis in the liver. Our studies unveiled novel DCLK1-controlled feed-forward signaling cascades involving calprotectin subunit S100A9 and NFκB activation as a driver of inflammation. Validation of transcriptome data suggests that DCLK1 co-expression with HCV induces BRM/SMARCA2 of SW1/SNF1 chromatin remodeling complexes. Frequently observed lymphoid aggregates including hepatic epithelial and stromal cells of internodular septa extensively express DCLK1 and S100A9. The DCLK1 overexpression also correlates with increased levels of S100A9, c-Myc, and BRM levels in HCV/HBV-positive patients with cirrhosis and HCC. DCLK1 silencing inhibits S100A9 expression and hepatoma cell migration. Normal human hepatocytes (NHH)-derived spheroids exhibit CSC properties. These results provide new insights into the molecular mechanism of the hepatitis B/C-virus induced liver inflammation and tumorigenesis via DCLK1-controlled networks. Thus, DCLK1 appears to be a novel therapeutic target for the treatment of inflammatory diseases and HCC. PMID:25948779

  3. Quinolinic Acid Responses during Interferon-α-Induced Depressive Symptomatology in Patients with Chronic Hepatitis C Infection - A Novel Aspect for Depression and Inflammatory Hypothesis

    PubMed Central

    Baranyi, Andreas; Meinitzer, Andreas; Breitenecker, Robert J.; Amouzadeh-Ghadikolai, Omid; Stauber, Rudolf; Rothenhäusler, Hans-Bernd

    2015-01-01

    Background The aim of this exploratory study is to gain for the first time a more comprehensive picture of the impact of changes of quinolinic acid concentrations on depressive symptomatology during and after IFN-α therapy. Methods The quinolinic acid concentrations of 35 HCV patients are examined in a prospective survey over the entire period of IFN-α treatment as well as three months later at six different times (baseline, one, three, six and nine months after the beginning of IFN-α treatment, and after the end of treatment). Results During IFN-α treatment Hamilton Depression Rating Scale scores rise significantly. At the same time there is greater activity of indoleamine 2,3-dioxygenase, with a resulting increase in plasma kynurenine concentrations. Compared to baseline values quinolinic acid concentrations increase significantly during therapy, reflecting an increased neurotoxic challenge. In addition, patients with higher scores in the Hamilton Depression Rating Scale at six and nine months after starting therapy show significantly higher levels of quinolinic acid concentration. Conclusions The increase of quinolinic acid during IFN-α therapy might contribute to depressive symptomatology through the neurotoxic challenge caused by quinolinic acid. Subsequently, our exploratory study results support the inflammatory hypothesis of depression. The awareness of relevant risk factors of IFN-α treatment-induced depression is essential to develop preventative treatment strategies. PMID:26368809

  4. 99th Dahlem Conference on Infection, Inflammation and Chronic Inflammatory Disorders: Host–microbe interactions in the gut: target for drug therapy, opportunity for drug discovery

    PubMed Central

    Shanahan, F

    2010-01-01

    The commensal microbiota, most of which resides in the gut, is an environmental regulator of mucosal and systemic immune maturation. Epidemiological studies suggest that changes in the microbiota may represent a link between a modern lifestyle and risk of certain immuno-allergic diseases. This suggests that the microbiota is an appropriate target for therapy or prophylaxis, the rationale for which is addressed here using inflammatory bowel disease as an example. It is also evident from comparative studies of germ-free and conventionally colonized animals that the microbiota is a source of regulatory signals for full development of the host. In some instances these signals have been defined molecularly, and may be suitable for exploitation in novel drug discovery. Most of the versatile drugs in common usage today were derived originally from living matter in the wider environment; could it be time to mine new drugs from microbial-derived signalling molecules in the inner environment of the gut? Several examples illustrate the potential of the gut microbiota as a rich repository from which bioactives with immunological impact can be mined, and translated to human health care or to animal husbandry. PMID:20415857

  5. Chronic hyperosmotic stress interferes with immune homeostasis in striped catfish (Pangasianodon hypophthalmus, S.) and leads to excessive inflammatory response during bacterial infection.

    PubMed

    Schmitz, Mélodie; Douxfils, Jessica; Mandiki, Syaghalirwa N M; Morana, Cédric; Baekelandt, Sébastien; Kestemont, Patrick

    2016-08-01

    Hyperosmotic stress has often been investigated from osmoregulation perspectives while the effects of such stress on the immune capacity remain largely unexplored. In this study, striped catfish were submitted to three salinity profiles (freshwater, low saline water, saline water) during 20 days, followed by infection with a virulent bacteria, Edwardsiella ictaluri, responsible for the enteric septicaemia of catfish. Osmoregulatory (plasma osmolality, gill Na(+)K(+)ATPase), immune (blood cells, lysozyme activity, complement activity, respiratory burst) parameters and mortality rate were investigated. In addition, abundances of heat shock protein 70 and high mobility group box 1 were explored. With elevated salinity, plasma osmolality severely increased while gill Na(+)K(+)ATPase slightly increased. Salinity alone stimulated the number of granulocytes, lysozyme activity and respiratory burst but depleted the number of thrombocytes. Salinity in combination with infection stimulated the number of monocytes and ACH50. On the contrary, erythrocytes, hematocrit, heat shock protein 70 and high mobility group box 1 did not significantly vary with salinity profiles. Then, salinity induced earlier onset on mortalities after E. ictaluri inoculation whereas cumulative mortality reach 79.2%, 67.0% and 91.7% respectively in freshwater, low saline water and saline water. In conclusion, salinity stimulates several immune functions in striped catfish but prolonged exposure to excessive hyperosmotic condition may lead to excessive inflammatory response and death. PMID:27346159

  6. Molecular cues guiding inflammatory responses.

    PubMed

    Barreiro, Olga; Martín, Pilar; González-Amaro, Roberto; Sánchez-Madrid, Francisco

    2010-05-01

    Alarm signals generated at inflammatory foci reach the vascular lumen to attract immune cells towards the affected tissue. Different leucocyte subsets decipher and integrate these complex signals in order to make adequate decisions for their migration towards the inflamed tissue. Soluble cues (cytokines and chemokines) and membrane receptors in both endothelium and leucocytes orchestrate the coordinated recruitment of specific inflammatory cell subsets. All these molecules are spatio-temporally organized in specialized structures at the luminal side of endothelium and the leucocyte membrane or are generated as chemical gradients in the damaged tissue. Thus, the repertoire of chemokines and their receptors as well as adhesion molecules expressed by each leucocyte subset determine their recruitment for participation in specific inflammatory pathologies. Whenever inflammatory signals are altered or misprocessed, inflammation can become chronic, causing extensive tissue damage. To combat chronic inflammation and autoimmune diseases, novel therapeutic strategies attempt to silence the predominant signals in each inflammatory scenario. In this review, we provide a general overview of all these aspects related to the molecular regulation of leucocyte guidance in inflammatory responses. PMID:20053659

  7. Attenuating effect of Acorus calamus extract in chronic constriction injury induced neuropathic pain in rats: an evidence of anti-oxidative, anti-inflammatory, neuroprotective and calcium inhibitory effects

    PubMed Central

    2011-01-01

    Background Acorus calamus (family: Araceae), is an indigenous plant, traditionally it is used as an ingredient of various cocktail preparations and for the management of severe inflammatory disorders in Indian system of medicine. Present study investigated the attenuating role of Acorus calamus plant extract in chronic constriction injury (CCI) of sciatic nerve induced peripheral neuropathy in rats. Methods Hot plate, plantar, Randall Selitto, Von Frey Hair, pin prick, acetone drop, photoactometer and rota-rod tests were performed to assess degree of thermal, radiant, mechanical, chemical sensation, spontaneous motor activity and motor co-ordination changes respectively, at different time intervals i.e., day 0, 1, 3, 6, 9, 12, 15, 18 and 21. Tissue myeloperoxidase, superoxide anion and total calcium levels were determined after 21st day to assess biochemical alterations. Histopathological evaluations were also performed. Hydroalcoholic extract of Acorus calamus (HAE-AC, 100 and 200 mg/kg, p.o.) and pregabalin (10 mg/kg, p.o.) were administered from the day of surgery for 14 days. Results CCI of sciatic nerve significantly induced thermal, radiant, mechanical hyperalgesia and thermal, chemical, tactile allodynia, along with increase in the levels of superoxide anion, total calcium and myeloperoxidase activity. Moreover significant histological changes were also observed. HAE-AC attenuated CCI induced development of painful behavioural, biochemical and histological changes in a dose dependent manner similar to that of pregabalin serving as positive control. Conclusions Acorus calamus prevented CCI induced neuropathy which may be attributed to its multiple actions including anti-oxidative, anti-inflammatory, neuroprotective and calcium inhibitory actions. PMID:21426568

  8. Characterizing Provenance in Visualization and Data Analysis: An Organizational Framework of Provenance Types and Purposes

    DOE PAGESBeta

    Ragan, Eric; Alex, Endert; Sanyal, Jibonananda; Chen, Jian

    2016-01-01

    While the primary goal of visual analytics research is to improve the quality of insights and findings, a substantial amount of research in provenance has focused on the history of changes and advances throughout the analysis process. The term, provenance, has been used in a variety of ways to describe different types of records and histories related to visualization. The existing body of provenance research has grown to a point where the consolidation of design knowledge requires cross-referencing a variety of projects and studies spanning multiple domain areas. We present an organizational framework of the different types of provenance informationmore » and purposes for why they are desired in the field of visual analytics. Our organization is intended to serve as a framework to help researchers specify types of provenance and coordinate design knowledge across projects. We also discuss the relationships between these factors and the methods used to capture provenance information. In addition, our organization can be used to guide the selection of evaluation methodology and the comparison of study outcomes in provenance research« less

  9. Characterizing Provenance in Visualization and Data Analysis: An Organizational Framework of Provenance Types and Purposes

    SciTech Connect

    Ragan, Eric; Alex, Endert; Sanyal, Jibonananda; Chen, Jian

    2016-01-01

    While the primary goal of visual analytics research is to improve the quality of insights and findings, a substantial amount of research in provenance has focused on the history of changes and advances throughout the analysis process. The term, provenance, has been used in a variety of ways to describe different types of records and histories related to visualization. The existing body of provenance research has grown to a point where the consolidation of design knowledge requires cross-referencing a variety of projects and studies spanning multiple domain areas. We present an organizational framework of the different types of provenance information and purposes for why they are desired in the field of visual analytics. Our organization is intended to serve as a framework to help researchers specify types of provenance and coordinate design knowledge across projects. We also discuss the relationships between these factors and the methods used to capture provenance information. In addition, our organization can be used to guide the selection of evaluation methodology and the comparison of study outcomes in provenance research

  10. Characterizing Provenance in Visualization and Data Analysis: An Organizational Framework of Provenance Types and Purposes.

    PubMed

    Ragan, Eric D; Endert, Alex; Sanyal, Jibonananda; Chen, Jian

    2016-01-01

    While the primary goal of visual analytics research is to improve the quality of insights and findings, a substantial amount of research in provenance has focused on the history of changes and advances throughout the analysis process. The term, provenance, has been used in a variety of ways to describe different types of records and histories related to visualization. The existing body of provenance research has grown to a point where the consolidation of design knowledge requires cross-referencing a variety of projects and studies spanning multiple domain areas. We present an organizational framework of the different types of provenance information and purposes for why they are desired in the field of visual analytics. Our organization is intended to serve as a framework to help researchers specify types of provenance and coordinate design knowledge across projects. We also discuss the relationships between these factors and the methods used to capture provenance information. In addition, our organization can be used to guide the selection of evaluation methodology and the comparison of study outcomes in provenance research. PMID:26340779

  11. PAV ontology: provenance, authoring and versioning

    PubMed Central

    2013-01-01

    Background Provenance is a critical ingredient for establishing trust of published scientific content. This is true whether we are considering a data set, a computational workflow, a peer-reviewed publication or a simple scientific claim with supportive evidence. Existing vocabularies such as Dublin Core Terms (DC Terms) and the W3C Provenance Ontology (PROV-O) are domain-independent and general-purpose and they allow and encourage for extensions to cover more specific needs. In particular, to track authoring and versioning information of web resources, PROV-O provides a basic methodology but not any specific classes and properties for identifying or distinguishing between the various roles assumed by agents manipulating digital artifacts, such as author, contributor and curator. Results We present the Provenance, Authoring and Versioning ontology (PAV, namespace http://purl.org/pav/): a lightweight ontology for capturing “just enough” descriptions essential for tracking the provenance, authoring and versioning of web resources. We argue that such descriptions are essential for digital scientific content. PAV distinguishes between contributors, authors and curators of content and creators of representations in addition to the provenance of originating resources that have been accessed, transformed and consumed. We explore five projects (and communities) that have adopted PAV illustrating their usage through concrete examples. Moreover, we present mappings that show how PAV extends the W3C PROV-O ontology to support broader interoperability. Method The initial design of the PAV ontology was driven by requirements from the AlzSWAN project with further requirements incorporated later from other projects detailed in this paper. The authors strived to keep PAV lightweight and compact by including only those terms that have demonstrated to be pragmatically useful in existing applications, and by recommending terms from existing ontologies when plausible. Discussion

  12. Anti-inflammatory Activity.

    PubMed

    2016-01-01

    Inflammation is the body's first response to infection or injury and is critical for both innate and adaptive immunity. It can be considered as part of the complex biological response of vascular tissues to harmful stimuli such as pathogens, damaged cells, or irritants. The search for natural compounds and phytoconstituents that are able to interfere with these mechanisms by preventing a prolonged inflammation could be useful for human health. Here, the anti-inflammatory properties of plant-based drugs are put together with both in vitro and acute (carrageenan, egg albumin and croton oil) and chronic (cotton pellet) in vivo models. PMID:26939273

  13. Chronic nandrolone administration promotes oxidative stress, induction of pro-inflammatory cytokine and TNF-α mediated apoptosis in the kidneys of CD1 treated mice

    SciTech Connect

    Riezzo, Irene; Turillazzi, Emanuela; Bello, Stefania; Cantatore, Santina; Cerretani, Daniela; Di Paolo, Marco; Fiaschi, Anna Ida; Frati, Paola; Neri, Margherita; Pedretti, Monica; Fineschi, Vittorio

    2014-10-01

    Nandrolone decanoate administration and strenuous exercise increase the extent of renal damage in response to renal toxic injury. We studied the role played by oxidative stress in the apoptotic response caused by nandrolone decanoate in the kidneys of strength-trained male CD1 mice. To measure cytosolic enzyme activity, glutathione peroxidase (GPx), glutathione reductase (GR) and malondialdehyde (MDA) were determined after nandrolone treatment. An immunohistochemical study and Western blot analysis were performed to evaluate cell apoptosis and to measure the effects of renal expression of inflammatory mediators (IL-1β, TNF-α) on the induction of apoptosis (HSP90, TUNEL). Dose-related oxidative damage in the kidneys of treated mice is shown by an increase in MDA levels and by a reduction of antioxidant enzyme GR and GPx activities, resulting in the kidney's reduced radical scavenging ability. Renal specimens of the treated group showed relevant glomeruli alterations and increased immunostaining and protein expressions, which manifested significant focal segmental glomerulosclerosis. The induction of proinflammatory cytokine expression levels was confirmed by Western blot analysis. Long-term administration of nandrolone promotes oxidative injury in the mouse kidneys. TNF-α mediated injury due to nandrolone in renal cells appears to play a role in the activation of both the intrinsic and extrinsic apoptosis pathways. - Highlights: • We analyze abuse of nandrolone decanoate in strength-trained male CD1 mice. • Nandrolone decanoate administration increases oxidative stress. • Increased cytokine expressions were observed. • Renal apoptosis was described. • Long-term administration of nandrolone promotes oxidative injury in mice kidney.

  14. Circulating Endothelial-Derived Apoptotic Microparticles in the Patients with Ischemic Symptomatic Chronic Heart Failure: Relevance of Pro-Inflammatory Activation and Outcomes

    PubMed Central

    Berezin, Alexander E.; Kremzer, Alexander A.; Samura, Tatayna A.; Martovitskaya, Yulia V.

    2014-01-01

    Background: Endothelial-derived apoptotic microparticles (EMPs) play a pivotal role in endothelial dysfunction in hronic Heart Failure (CHF). Objectives: The present study aimed to evaluate the association between EMPs and pro-inflammatory biomarkers, clinical status, and outcomes in the patients with ischemic CHF. Patients and Methods: This study was conducted on 154 patients with ischemic symptomatic moderate-to-severe CHF on discharge from hospital. The observation period was up to 3 years. Circulating NT-pro-BNP, TNF-alpha, sFas, and sFas ligand were determined at baseline. Flow cytometry analysis was used for quantifying the number of EMPs. All-cause mortality, CHF-related death, and CHD-re-hospitalization rate were examined. The data were analyzed using descriptive statistics, Receive Operation Characteristic Curve (ROC), and logistic regression analysis. Besides, P < 0.05 was considered as statistically significant. Results: During a median follow-up of 2.18 years, 21 participants died and 106 subjects were hospitalized repetitively. The results showed a significant difference between the patients with a large number of EMPs (> 0.514 n/mL) and those with a low level of the biomarker (< 0.514 n/mL) regarding their survival. The number of circulating EPMs independently predicted all-cause mortality (OR = 1.58; 95% CI = 1.20 – 1.88; P = 0.001), CHF-related death (OR = 1.22; 95% CI: 1.12 – 1.36; P < 0.001), and CHF-related re-hospitalization (OR = 1.20; 95% CI: 1.11 – 1.32; P < 0.001). Conclusions: Among the patients with symptoms of CHF, increased number of circulating EMPs was associated with increased 3-year CHF-related death, all-cause mortality, and risk of recurrent hospitalization due to CHF. PMID:25177675

  15. Incorporation of n-3 PUFA and γ-linolenic acid in blood lipids and red blood cell lipids together with their influence on disease activity in patients with chronic inflammatory arthritis - a randomized controlled human intervention trial

    PubMed Central

    2011-01-01

    Background and aim Marine n-3 fatty acids and γ-linolenic acid both have anti-inflammatory effects and may be useful to help treat inflammatory diseases. The effects of these alone or combined were examined in patients with arthritis in a randomized controlled trial. Design Patients with rheumatoid arthritis or psoriatic arthritis were randomized into four groups in a double-blind, placebo-controlled parallel designed study. Patients received the respective capsules (1: 3.0 g n-3 LC-PUFA/d; 2: 3.2 g γ-linolenic acid/d; 3: 1.6 g n-3 LC-PUFA + 1.8 g γ-linolenic acid/d; 4: 3.0 g olive oil) for a twelve week period. Clinical status was evaluated and blood samples were taken at the beginning and at the end of the period. Differences before and after intervention were tested with paired t-test or with Wilcoxon test for non-normal data distribution. Results 60 patients (54 rheumatoid arthritis, 6 psoriatic arthritis) were randomised, 47 finished per protocol. In group 1, the ratio of arachidonic acid (AA)/eicosapentaenoic acid (EPA) decreased from 6.5 ± 3.7 to 2.7 ± 2.1 in plasma lipids and from 25.1 ± 10.1 to 7.2 ± 4.7 in erythrocyte membranes (p ≤ 0.001). There was no significant influence on AA/EPA ratio due to interventions in group 2-4. In group 2, the intake of γ-linolenic acid resulted in a strong rise of γ-linolenic acid and dihomo-γ-linolenic acid concentrations in plasma lipids, cholesteryl esters, and erythrocyte membranes. The combination of n-3 LC-PUFA and γ-linolenic acid (group 3) led to an increase of γ-linolenic acid and dihomo-γ-linolenic acid concentrations in plasma lipids, cholesteryl esters, and erythrocyte mem-branes. This increase was only half of that in group 2. Conclusions Incorporation of eicosanoid precursor FAs was influenced by an intake of n-3 LC-PUFA and γ-linolenic acid suggesting a possible benefit for therapy of chronic inflammatory diseases. Trial Registration ClinicalTrials NCT01179971 PMID:21816071

  16. Tracking Files Using the Kepler Provenance Framework

    SciTech Connect

    Pierre, Mouallem; Vouk, Mladen; Klasky, Scott A; Tchoua, Roselyne B; Podhorszki, Norbert

    2009-01-01

    Workflow Management Systems (WFMS), such as Kepler, are proving to be an important tool in scientific problem solving. They can automate and manage complex processes and huge amounts of data produced by petascale simulations. Typically, the produced data need to be properly visualized and analyzed by scientists in order to achieve the desired scientific goals. Both run-time and post analysis may benefit from, even require, additional meta-data - provenance information. One of the challenges in this context is the tracking of the data files that can be produced in very large numbers during stages of the workflow, such as visualizations. The Kepler provenance framework collects all or part of the raw information flowing through the workflow graph. This information then needs to be further parsed to extract meta-data of interest. This can be done through add-on tools and algorithms. We show how to automate tracking specific information such as data files locations.

  17. Tracking Files Using the Kepler Provenance Framework

    SciTech Connect

    Mouallem, P. A.; Tchoua, Roselyne B; Klasky, Scott A; Podhorszki, Norbert; Vouk, M. A.

    2009-01-01

    Workflow Management Systems (WFMS), such as Kepler, are prov- ing to be an important tool in scientific problem solving. They can automate and manage complex processes and huge amounts of data produced by petas- cale simulations. Typically, the produced data need to be properly visualized and analyzed by scientists in order to achieve the desired scientific goals. Both run-time and post analysis may benefit from, even require, additional meta-data provenance information. One of the challenges in this context is the tracking of the data files that can be produced in very large numbers during stages of the workflow, such as visualizations. The Kepler provenance framework collects all or part of the raw information flowing through the workflow graph. This infor- mation then needs to be further parsed to extract meta-data of interest. This can be done through add-on tools and algorithms. We show how to automate track- ing specific information such as data files locations.

  18. Tracking Files in the Kepler Provenance Framework

    SciTech Connect

    Mouallem, Pierre A; Klasky, Scott A; Podhorszki, Norbert; Vouk, Mladen

    2009-01-01

    Workflow Management Systems (WFMS), such as Kepler, are proving to be an important tool in scientific problem solving. They can automate and manage complex processes and huge amounts of data produced by petascale simulations. Typically, the produced data need to be properly visualized and analyzed by scientists in order to achieve the desired scientific goals. Both run-time and post analysis may benefit from, even require, additional meta-data - provenance information. One of the challenges in this context is the tracking of the data files that can be produced in very large numbers during stages of the workflow, such as visualizations. The Kepler provenance framework collects all or part of the raw information flowing through the workflow graph. This information then needs to be further parsed to extract meta-data of interest. This can be done through add-on tools and algorithms. We show how to automate tracking specific information such as data files locations.

  19. Obsidian provenance research in the Americas.

    PubMed

    Glascock, Michael D

    2002-08-01

    The characterization of archaeological materials to support provenance research has grown rapidly over the past few decades. Volcanic obsidian has several unique properties that make it the ideal archaeological material for studying prehistoric trade and exchange. This Account describes our laboratory's development of a systematic methodology for the characterization of obsidian sources and artifacts from Mesoamerica and other regions of North and South America in support of archaeological research. PMID:12186565

  20. Inflammatory Cytokines, Endothelial Function, and Chronic Allograft Vasculopathy in Children: An Investigation of the Donor and Recipient Vasculature After Heart Transplantation.

    PubMed

    Fenton, M; Simmonds, J; Shah, V; Brogan, P; Klein, N; Deanfield, J; Burch, M

    2016-05-01

    Chronic allograft vasculopathy (CAV) limits the lifespan of pediatric heart transplant recipients. We investigated blood markers of inflammation, endothelial dysfunction, and damage to both the native and transplanted vasculature in children after heart transplantation. Serum samples were taken from pediatric heart transplant recipients for markers of inflammation and endothelial activation. The systemic vasculature was investigated using brachial artery flow-mediated dilatation and carotid artery intima-medial hyperplasia. CAV was investigated using intravascular ultrasound. Mean intima-media thickness (mIMT) > 0.5 mm was used to define significant CAV. Forty-eight children (25 male) aged 8-18 years were enrolled in the study. Patients were a median (interquartile range) 4.1 (2.2-8.7) years after transplant. Patients had increased levels of circulating IL6 (3.86 [2.84-4.95] vs. 1.66 [1.22-2.63] p < 0.0001), vascular cell adhesion molecule 1 (539 [451-621] vs. 402 [342-487] p < 0.001), intracellular adhesion molecule 1 305 (247-346) vs. 256 (224-294) p = 0.002 and thrombomodulin (7.1 [5.5-8.1] vs. 3.57 [3.03-4.71] p < 0.0001) and decreased levels of tumor necrosis factor-α, E selectin, and P selectin, compared with controls. The systemic vasculature was unaffected. Patients with severe CAV had raised serum von Willebrand factor and decreased serum thrombomodulin. Posttransplant thrombomodulin levels are elevated after transplant but significantly lower in those with mIMT > 0.5 mm. This suggests that subclinical inflammation is present and that natural anticoagulant/thrombomodulin activity is important after transplant. PMID:26614396

  1. 99th Dahlem Conference on Infection, Inflammation and Chronic Inflammatory Disorders: Immune therapies of type 1 diabetes: new opportunities based on the hygiene hypothesis

    PubMed Central

    Chatenoud, L; You, S; Okada, H; Kuhn, C; Michaud, B; Bach, J-F

    2010-01-01

    Insulin-dependent (type 1) diabetes is a prototypic organ-specific autoimmune disease resulting from the selective destruction of insulin-secreting β cells within pancreatic islets of Langerhans by an immune-mediated inflammation involving autoreactive CD4+ and CD8+ T lymphocytes which infiltrate pancreatic islets. Current treatment is substitutive, i.e. chronic use of exogenous insulin which, in spite of significant advances, is still associated with major constraints (multiple daily injections, risks of hypoglycaemia) and lack of effectiveness over the long term in preventing severe degenerative complications. Finding a cure for autoimmune diabetes by establishing effective immune-based therapies is a real medical health challenge, as the disease incidence increases steadily in industrialized countries. As the disease affects mainly children and young adults, any candidate immune therapy must therefore be safe and avoid a sustained depression of immune responses with the attendant problems of recurrent infection and drug toxicity. Thus, inducing or restoring immune tolerance to target autoantigens, controlling the pathogenic response while preserving the host reactivity to exogenous/unrelated antigens, appears to be the ideal approach. Our objective is to review the major progress accomplished over the last 20 years towards that aim. In addition, we would like to present another interesting possibility to access new preventive strategies based on the ‘hygiene hypothesis’, which proposes a causal link between the increasing incidence of autoimmune diseases, including diabetes, and the decrease of the infectious burden. The underlying rationale is to identify microbial-derived compounds mediating the protective activity of infections which could be developed therapeutically. PMID:20415859

  2. Iron deficiency: the hidden miscreant in inflammatory bowel disease.

    PubMed

    Allocca, Mariangela; Fiorino, Gionata; Danese, Silvio

    2014-01-01

    Iron deficiency (ID) and anemia of chronic diseases (ACD) are the most common causes of anemia in inflammatory bowel disease (IBD), and frequently coexist. In these circumstances, detection of ID may be difficult as inflammation influences the parameters of iron metabolism. The prevalence of iron deficiency anemia (IDA) ranges between 36% and 76% in this population of patients. Anemia may impair physical condition, quality of life (QOL), and cognitive function, negatively affecting almost every aspect of daily life. Furthermore, it may be one of the causes of death in IBD. Consequently, iron replacement therapy should be initiated as soon as ID or IDA is detected, together with the treatment of underlying inflammation. Oral iron therapy is a simple and cheap treatment, but often is poorly tolerated and may worsen the intestinal damage. Moreover, in inflammatory states, duodenal iron absorption is blocked by a cytokine-mediated mechanism. Consequently, intravenous iron therapy is preferred in the presence of severe anemia, intolerance or lack of response to oral iron, and moderately to severely active disease. Recently, new intravenous iron compounds (iron carboxymaltose, iron isomaltoside 1000, ferumoxytol) have become available. Iron carboxymaltose has been shown to be safe and effective in IBD patients with IDA. Furthermore, it allows for rapid administration of high single doses, saving time and costs. If proven to be efficacious and well tolerated, it may become the standard therapy in the near future. PMID:25213175

  3. Correlation of the Beta-Trace Protein and Inflammatory Cytokines with Magnetic Resonance Imaging in Chronic Subdural Hematomas : A Prospective Study

    PubMed Central

    Park, Ki-Su; Park, Seong-Hyun; Hwang, Sung-Kyoo; Kim, Chaekyung

    2015-01-01

    Objective Magnetic resonance imaging (MRI) of chronic subdural hematoma (CSDH) detects various patterns, which can be attributed to many factors. The purpose of this study was to measure the level of interleukin-6 (IL-6), interleukin-8 (IL-8), and highly specific protein [beta-trace protein (βTP)] for cerebrospinal fluid (CSF) in CSDHs, and correlate the levels of these markers with the MRI findings. Methods Thirty one patients, treated surgically for CSDH, were divided on the basis of MRI findings into hyperintense and non-hyperintense groups. The concentrations of IL-6, IL-8, and βTP in the subdural fluid and serum were measured. The βTP was considered to indicate an admixture of CSF to the subdural fluid if βTP in the subdural fluid (βTPSF)/βTP in the serum (βTPSER)>2. Results The mean concentrations of IL-6 and IL-8 of the hyperintense group (n=17) of T1-WI MRI were 3975.1±1040.8 pg/mL and 6873.2±6365.4 pg/mL, whereas them of the non-hyperintense group (n=14) were 2173.5±1042.1 pg/mL and 2851.2±6267.5 pg/mL (p<0.001 and p=0.004). The mean concentrations of βTPSF and the ratio of βTPSF/βTPSER of the hyperintense group (n=13) of T2-WI MRI were 7.3±2.9 mg/L and 12.6±5.4, whereas them of the non-hyperintense group (n=18) were 4.3±2.3 mg/L and 7.5±3.9 (p=0.011 and p=0.011). Conclusion The hyperintense group on T1-WI MRI of CSDHs exhibited higher concentrations of IL-6 and IL-8 than non-hyperintense group. And, the hyperintese group on T2-WI MRI exhibited higher concentrations of βTPSF and the ratio of βTPSF/βTPSER than non-hyperintense group. These findings appear to be associated with rebleeding and CSF admixture in the CSDHs. PMID:25932289

  4. Quantitative hepatitis B core antibody level is associated with inflammatory activity in treatment-naïve chronic hepatitis B patients.

    PubMed

    Li, Min-Ran; Lu, Jian-Hua; Ye, Li-Hong; Sun, Xing-Li; Zheng, Yan-Hua; Liu, Zhi-Quan; Zhang, Hai-Cong; Liu, Yun-Yan; Lv, Ying; Huang, Yan; Dai, Er-Hei

    2016-08-01

    Previous studies have shown that hepatitis B core antibody (anti-HBc) levels vary during different phases of disease in treatment-naïve chronic hepatitis B (CHB) patients and can be used as a predictor of both interferon-α and nucleoside analogue therapy response. However, there is no information on the association between the quantitative serum anti-HBc (qAnti-HBc) level and liver inflammation in CHB patients. Therefore, we investigated these relationships in a large cohort of treatment-naïve CHB patients. A total of 624 treatment-naïve CHB patients were included in the study. The serum qAnti-HBc level was moderately correlated with ALT and AST levels (P < 0.001) in both hepatitis B e antigen-positive (HBeAg [+]) and HBeAg-negative (HBeAg [-]) CHB patients. CHB patients with no to mild inflammation (G0-1) had significantly lower serum qAnti-HBc levels than patients with moderate to severe inflammation (G2-4) (P < 0.001). Receiver operating characteristic analysis suggested that a serum qAnti-HBc cut-off value of 4.36 log10 IU/mL provided a sensitivity of 71.68%, specificity of 73.81%, positive predictive value of 78.43%, and negative predictive value of 66.24% in HBeAg (+) CHB patients with moderate to severe inflammation (G≥2). A cut-off value of 4.62 log10 IU/mL provided a sensitivity of 54.29%, specificity of 90.00%, positive predictive value of 95.00%, and negative predictive value of 36.00% in HBeAg (-) CHB patients with moderate to severe inflammation (G≥2). Serum qAnti-HBc levels were positively associated with liver inflammation grade. Furthermore, we identified optimal serum qAnti-HBc cut-off values for the prediction of inflammation activity in both HBeAg (+) and HBeAg (-) treatment-naïve CHB patients. PMID:27559949

  5. Functions and possible provenance of primordial proteins.

    PubMed

    Sommer, Andrei P; Miyake, Norimune; Wickramasinghe, N Chandra; Narlikar, Jayant V; Al-Mufti, Shirwan

    2004-01-01

    Nanobacteria or living nanovesicles are of great interest to the scientific community because of their dual nature: on the one hand, they appear as primal biosystems originating life; on the other hand, they can cause severe diseases. Their survival as well as their pathogenic potential is apparently linked to a self-synthesized protein-based slime, rich in calcium and phosphate (when available). Here, we provide challenging evidence for the occurrence of nanobacteria in the stratosphere, reflecting a possibly primordial provenance of the slime. An analysis of the slime's biological functions may lead to novel strategies suitable to block adhesion modalities in modern bacterial populations. PMID:15595742

  6. Enterocutaneous Fistula: Proven Strategies and Updates.

    PubMed

    Gribovskaja-Rupp, Irena; Melton, Genevieve B

    2016-06-01

    Management of enterocutaneous fistula represents one of the most protracted and difficult problems in colorectal surgery with substantial morbidity and mortality rates. This article summarizes the current classification systems and successful management protocols, provides an in-depth review of fluid resuscitation, sepsis control, nutrition management, medication management of output quantity, wound care, nonoperative intervention measures, operative timeline, and considerations, and discusses special considerations such as inflammatory bowel disease and enteroatmospheric fistula. PMID:27247538

  7. Chronic pancreatitis

    MedlinePlus

    Chronic pancreatitis - chronic; Pancreatitis - chronic - discharge; Pancreatic insufficiency - chronic; Acute pancreatitis - chronic ... abuse over many years. Repeated episodes of acute pancreatitis can lead to chronic pancreatitis. Genetics may be ...

  8. Sphingolipid metabolites in inflammatory disease

    PubMed Central

    Maceyka, Michael; Spiegel, Sarah

    2015-01-01

    Sphingolipids are ubiquitous building blocks of eukaryotic cell membranes. Progress in our understanding of sphingolipid metabolism, state-of-the-art sphingolipidomic approaches and animal models have generated a large body of evidence demonstrating that sphingolipid metabolites, particularly ceramide and sphingosine-1-phosphate, are signalling molecules that regulate a diverse range of cellular processes that are important in immunity, inflammation and inflammatory disorders. Recent insights into the molecular mechanisms of action of sphingolipid metabolites and new perspectives on their roles in regulating chronic inflammation have been reported. The knowledge gained in this emerging field will aid in the development of new therapeutic options for inflammatory disorders. PMID:24899305

  9. Actualistic Ophiolite Provenance: The Cyprus Case.

    PubMed

    Garzanti; Andò; Scutellà

    2000-03-01

    The island of Cyprus represents an excellent site to assess quantitatively petrologic clastic response to actively obducting oceanic sources in order to define an actualistic reference for ophiolite provenance, in terms of framework composition and heavy mineral suites. An improved methodology, an extension of the classic ternary QFL logic to include a wider spectrum of key indexes and ratios, provides an accurate synthesis of modal data and allows differentiation of three main petrographic provinces and at least seven subprovinces. Diagnostic signatures of detritus from various levels of an oceanic lithospheric source, and criteria for distinguishing provenance from suprasubduction versus mid-oceanic ophiolites are also outlined. Modern sands derived from the Troodos Ophiolite contain variable proportions of largely pelagic carbonate to chert, boninite to basalt, diabase to metabasite, plagiogranite to gabbroic, and cumulate grains supplied from progressively deeper-seated levels of the multilayered oceanic crust. Dense minerals are mainly clinopyroxenes (diopside), prevailing over orthopyroxenes (enstatite, hypersthene, clinoenstatite), hornblende, tremolite/actinolite, and epidote. Where serpentinized mantle harzburgites have been unroofed, detritus is markedly enriched in cellular serpentinite grains and enstatite, with still negligible olivine and spinel. Sedimentaclastic sands dominated by chert (Mamonia Province) or carbonate grains (Kyrenia Province) are deposited along the southern and northern shores of the island, respectively. Compositions of Cyprus sands are virtually unaffected by climatic, sedimentary, or anthropic processes; recycling of sandstones from foreign sources is a major process only in the Karpaz Peninsula. Petrographic analysis also provides an independent mean to identify prevalent directions of longshore sand transport. PMID:10736270

  10. Data Provenance in Photogrammetry Through Documentation Protocols

    NASA Astrophysics Data System (ADS)

    Carboni, N.; Bruseker, G.; Guillem, A.; Bellido Castañeda, D.; Coughenour, C.; Domajnko, M.; de Kramer, M.; Ramos Calles, M. M.; Stathopoulou, E. K.; Suma, R.

    2016-06-01

    Documenting the relevant aspects in digitisation processes such as photogrammetry in order to provide a robust provenance for their products continues to present a challenge. The creation of a product that can be re-used scientifically requires a framework for consistent, standardised documentation of the entire digitisation pipeline. This article provides an analysis of the problems inherent to such goals and presents a series of protocols to document the various steps of a photogrammetric workflow. We propose this pipeline, with descriptors to track all phases of digital product creation in order to assure data provenance and enable the validation of the operations from an analytic and production perspective. The approach aims to support adopters of the workflow to define procedures with a long term perspective. The conceptual schema we present is founded on an analysis of information and actor exchanges in the digitisation process. The metadata were defined through the synthesis of previous proposals in this area and were tested on a case study. We performed the digitisation of a set of cultural heritage artefacts from an Iron Age burial in Ilmendorf, Germany. The objects were captured and processed using different techniques, including a comparison of different imaging tools and algorithms. This augmented the complexity of the process allowing us to test the flexibility of the schema for documenting complex scenarios. Although we have only presented a photogrammetry digitisation scenario, we claim that our schema is easily applicable to a multitude of 3D documentation processes.

  11. [Chronic nonbacterial osteomyelitis].

    PubMed

    Keskitalo, Paula; Remes-Pakarinen, Terhi; Vähäsalo, Paula; Niinimäki, Jaakko; Kröger, Liisa

    2016-01-01

    Chronic nonbacterial osteomyelitis is an autoinflammatory disease occurring mainly in children and adolescents, typically involving recurrent or persistent osteitic foci. The symptom is bone pain, possibly accompanied by soft tissue tenderness. Some patients exhibit symptoms of systemic inflammation. The. precise etiology of the disease is not known, but an imbalance of inflammatory and anti-inflammatory cytokines is presumed to play a role in the development of the disease. While an anti-inflammatory analgesic is in most cases sufficient to calm down the osteitis, the use of corticosteroids, anti- TNF-a inhibitors or bisphosphonates is required in some cases. PMID:26939487

  12. Standardized wellheads proven economical for subsea operations

    SciTech Connect

    Moreira, C.C.; Silva Paulo, C.A. )

    1994-05-02

    A standardization program for subsea wellheads and completion equipment has made development of Brazil's offshore fields more economical and efficient. The resulting operational flexibility associated with the use of field-proven equipment and procedures saves rig time and can reduce production loss during workovers. Additionally, investments can be rationalized economically by installing part of the completion equipment at the end of the drilling job and then delaying purchase and installation of the christmas tree and the flow lines until installation of the production platform. Savings are also realized from the reduction in the number of spare parts and tools. Moreover, the savings related to improved operations exceed considerably those from equipment acquisition and storage. Thus, the greatest benefit is the operational flexibility. The paper discusses initial standards, the subsea programs, philosophy, implementation, diver-assisted trees, diverless trees, and economics.

  13. Titian: Data Provenance Support in Spark

    PubMed Central

    Interlandi, Matteo; Shah, Kshitij; Tetali, Sai Deep; Gulzar, Muhammad Ali; Yoo, Seunghyun; Kim, Miryung; Millstein, Todd; Condie, Tyson

    2015-01-01

    Debugging data processing logic in Data-Intensive Scalable Computing (DISC) systems is a difficult and time consuming effort. Today’s DISC systems offer very little tooling for debugging programs, and as a result programmers spend countless hours collecting evidence (e.g., from log files) and performing trial and error debugging. To aid this effort, we built Titian, a library that enables data provenance—tracking data through transformations—in Apache Spark. Data scientists using the Titian Spark extension will be able to quickly identify the input data at the root cause of a potential bug or outlier result. Titian is built directly into the Spark platform and offers data provenance support at interactive speeds—orders-of-magnitude faster than alternative solutions—while minimally impacting Spark job performance; observed overheads for capturing data lineage rarely exceed 30% above the baseline job execution time. PMID:26726305

  14. Treatment of chronic urticaria.

    PubMed

    Jurakić Toncić, Ruzica; Lipozencić, Jasna; Marinović, Branka

    2009-01-01

    Urticaria is a disorder characterized by rapid onset of localized swelling of the skin or mucosa, called wheals or urtica. According to frequency and duration, urticaria can be divided into acute and chronic type. Chronic urticaria is any type of urticaria occurring every day or twice per week, lasting longer than 6 weeks. Chronic urticaria is a common disorder and estimated prevalence is 1% of the population. Also, it is not rare in childhood. The pathogenesis of chronic urticaria has not yet been completely understood. Chronic urticaria is a heterogeneous group of disorders, and according to the etiology and cause, several groups of chronic urticaria are distinguished, i.e. autoimmune, pseudoallergic, infection-related, physical urticaria, vasculitis urticaria and idiopathic urticaria. Treatment and management of chronic urticaria can be non-pharmacological and pharmacological, and sometimes it is not possible to control the disease with antihistamines only, which are considered to be the mainstay of treatment. In severe cases of chronic urticaria, especially if autoimmunity has been proven, several authors describe different modules of immunomodulation: cyclosporine, cyclophosphamide, mycophenolate-mofetil, omalizumab, plasmapheresis, systemic corticosteroids, and immunoglobulin therapy. This article primarily addresses the treatment of chronic idiopathic and autoimmune urticaria. PMID:20021986

  15. Scientific Workflows + Provenance = Better (Meta-)Data Management

    NASA Astrophysics Data System (ADS)

    Ludaescher, B.; Cuevas-Vicenttín, V.; Missier, P.; Dey, S.; Kianmajd, P.; Wei, Y.; Koop, D.; Chirigati, F.; Altintas, I.; Belhajjame, K.; Bowers, S.

    2013-12-01

    The origin and processing history of an artifact is known as its provenance. Data provenance is an important form of metadata that explains how a particular data product came about, e.g., how and when it was derived in a computational process, which parameter settings and input data were used, etc. Provenance information provides transparency and helps to explain and interpret data products. Other common uses and applications of provenance include quality control, data curation, result debugging, and more generally, 'reproducible science'. Scientific workflow systems (e.g. Kepler, Taverna, VisTrails, and others) provide controlled environments for developing computational pipelines with built-in provenance support. Workflow results can then be explained in terms of workflow steps, parameter settings, input data, etc. using provenance that is automatically captured by the system. Scientific workflows themselves provide a user-friendly abstraction of the computational process and are thus a form of ('prospective') provenance in their own right. The full potential of provenance information is realized when combining workflow-level information (prospective provenance) with trace-level information (retrospective provenance). To this end, the DataONE Provenance Working Group (ProvWG) has developed an extension of the W3C PROV standard, called D-PROV. Whereas PROV provides a 'least common denominator' for exchanging and integrating provenance information, D-PROV adds new 'observables' that described workflow-level information (e.g., the functional steps in a pipeline), as well as workflow-specific trace-level information ( timestamps for each workflow step executed, the inputs and outputs used, etc.) Using examples, we will demonstrate how the combination of prospective and retrospective provenance provides added value in managing scientific data. The DataONE ProvWG is also developing tools based on D-PROV that allow scientists to get more mileage from provenance metadata

  16. Anti cytokine therapy in chronic inflammatory arthritis.

    PubMed

    Thompson, Charlotte; Davies, Ruth; Choy, Ernest

    2016-10-01

    This is a review looking at anti cytokine therapy in Rheumatoid Arthritis (RA), Psoriatic Arthritis (PSA) and Ankylosing Spondylitis (AS). The review explores the similarities and differences in the clinical features, as well as treatments and cytokines involved in the development and propagation of the disease. Particular attention is paid to TNFα inhibitors IL-1ra, IL-6 and JAK kinase Inhibitors, anti IL23 and IL-12 and the new developments with anti-IL-17. PMID:27497159

  17. Current evidence of extracorporeal shock wave therapy in chronic Achilles tendinopathy.

    PubMed

    Gerdesmeyer, Ludger; Mittermayr, Rainer; Fuerst, Martin; Al Muderis, Munjed; Thiele, Richard; Saxena, Amol; Gollwitzer, Hans

    2015-12-01

    Chronic Achilles tendinopathy has been described as the most common overuse injury in sports medicine. Several treatment modalities such as activity modification, heel lifts, arch supports, stretching exercises, nonsteroidal anti-inflammatories, and eccentric loading are known as standard treatment mostly without proven evidence. After failed conservative therapy, invasive treatment may be considered. Extracorporeal shock wave therapy (ESWT) has been successfully used in soft-tissue pathologies like lateral epicondylitis, plantar fasciitis, tendinopathy of the shoulder and also in bone and skin disorders. Conclusive evidence recommending ESWT as a treatment for Achilles tendinopathy is still lacking. In plantar fasciitis as well as in calcific shoulder tendinopathy shock wave therapy is recently the best evaluated treatment option. This article analysis the evidence based literature of ESWT in chronic Achilles tendinopathy. Recently published data have shown the efficacy of focused and radial extracorporeal shock wave therapy. PMID:26327530

  18. Dietary modulation of the inflammatory cascade.

    PubMed

    Dawson, Dolphus R; Branch-Mays, Grishondra; Gonzalez, Octavio A; Ebersole, Jeffrey L

    2014-02-01

    Dietary supplementation has traditionally consisted of adding vitamins and/or minerals to correct or prevent a nutritional deficiency. When supplementing the diet with other inflammatory mediators, such as essential fatty acids, there is an adjunctive benefit to the standard therapies used in the control of chronic inflammatory diseases such as Crohn's disease or rheumatoid arthritis. This review focuses on the strategies utilized for therapeutic modulation of the inflammatory cascade through dietary supplementation with specific biomolecules. Examples of how these biomolecules affect local and systemic immune responses to chronic inflammation are examined. In particular, an overview of the literature identifying the potential to modify the host response to chronic periodontitis is provided. PMID:24320963

  19. Multiple sclerosis, an autoimmune inflammatory disease: prospects for its integrative management.

    PubMed

    Kidd, P M

    2001-12-01

    Multiple sclerosis (MS) is aptly named for the many scars it produces in the brain and spinal cord. A sometimes fatal, often debilitating disease, MS features autoimmune inflammatory attack against the myelin insulation of neurons. Thymus derived (T) cells sensitized against myelin self-antigens secrete tumor necrosis factor, cytokines, prostaglandins, and other inflammatory mediators that strip away the myelin and sometimes destroy the axons. Familial and twin inheritance studies indicate MS is mildly heritable. No single MS locus has been identified, but an HLA haplotype has been implicated. Unique geographic distribution of the disease is best attributed to some combination of vitamin D abnormality and dietary patterns. No pharmaceutical or other therapies exist that confer prolonged remission on MS, and obvious interrelationships between toxic, infectious, and dietary factors make a persuasive case for integrative management. The time-proven MS diet meticulously keeps saturated fats low, includes three fish meals per week, and eliminates allergenic foods. Dietary supplementation for MS minimally requires potent vitamin supplementation, along with the thiol antioxidants, the anti-inflammatory omega-3 fatty acids, and adaptogenic phytonutrients. Gut malabsorption and dysbiosis can be corrected using digestive enzymes and probiotics. Long-term hyperbaric oxygen therapy can slow or remit the disease. Transdermal histamine offers promise, and adenosine monophosphate may sometimes benefit. Chronic viruses and other infectious load must be aggressively treated and exercise should maintain muscle tone and balance. Early intervention with integrative modalities has the potential to make MS a truly manageable disease. PMID:11804546

  20. Mineralogical and geochemical evidence of Quachita provenance

    SciTech Connect

    Sutton, S.J. . Dept. of Earth Resources); Land, L.S.; Hutson, F. . Dept. of Geological Science); Awwiller, D.N. . Dept. of Geology)

    1994-03-01

    Provenance of the extremely thick Ouachita flysch has not been specifically identified, despite several recent studies. Detrital mineral compositions, Sm-Nd model ages, and single zircon dates strongly suggest that several sources contributed sediment that became well-mixed before deposition. Sm-Nd model ages are nearly uniform for flysch samples, regardless of geographic position or exact stratigraphic position. These ages appear to rule out significant contribution by a Paleozoic island arc, and suggest a single source, multiple sources with similar model ages, or thorough mixing of sources with different model ages. In contrast, single zircon ages are variable, including Archean, Proterozoic, and Paleozoic ages. These ages indicate multiple sediment sources, including some external to North America. The zircon ages, however, may not be generally representative of Ouachita sediment sources because they were obtained on zircons far larger than typical Ouachita detrital zircons. The Sm-Nd model ages and single zircon ages can both be explained if sediment entering the Ouachita Trough came from multiple sources, but was already thoroughly mixed before entering the trough. Such mixing is also suggested by detrital mineral analyses. Muscovite, garnet, and tourmaline have been analyzed.

  1. On Estimating Provenances of Lunar Highland Materials

    NASA Technical Reports Server (NTRS)

    Haskin, Larry A.; Jolliff, Brad L.

    1998-01-01

    That even relatively small impacts can spread material across the face of the Moon is evident from the rays of Tycho. Tycho ejecta triggered the landslide that produced the light mantle deposit at Apollo 17 and perhaps excavated the Central Valley craters there. Basin-sized impacts appear to follow the same scaling laws as smaller impacts, as indicated by the satisfaction of a geophysical model. These giant impacts rearranged huge amounts of premare material, complicating the determination of provenance of materials collected from the highlands. We have developed a model to estimate the probability that material at a particular location might derive from a given basin or large crater. This model is based on crater scaling laws, and effects of secondary cratering. Because it accounts for the volume of primary ejecta from the basin-forming transient craters and the excavating and mixing effects of these ejecta with the substrate onto which they fall, it gives much thicker deposits than an early work. Our modeling takes into account the distribution of sizes of primary ejecta fragments (PriFrags) to obtain the probability at a given site for a deposit of a particular thickness and with a fraction of PriFrags.

  2. Provenance of Norphlet sandstone, northern Gulf Coast

    SciTech Connect

    Ryan, W.P.; Ward, W.C.; Kuglar, R.L.

    1987-09-01

    The Upper Jurassic Norphlet sandstone of the northern Gulf Coast is predominantly subarkose, with some arkose in the eastern area and sublitharenite and quartzarenite in the western area. Despite great depths of burial and despite feldspar and rock-fragment constituents, diagenesis has not appreciably altered the composition of Norphlet sandstone. Therefore, reconstruction of original composition of Norphlet sandstone presented little difficulty. Variation in detrital modes of the Norphlet suggests compositionally distinct source terranes. Samples from Florida, Alabama, and Mississippi reflect the influence of metamorphic and plutonic rocks of the Appalachian Piedmont Province and of Triassic-Jurassic volcanic rocks. Sandstones in east Texas, northern Louisiana, and southern Arkansas were derived from sedimentary and metasedimentary rocks of the Ouachita system. The Arbuckle Mountains and Llano uplift may have supplied trace amounts of quartzo-feldspathic and volcanic-rock fragments to the extreme western part of the study area. Norphlet sandstones represent a mixture of collision-orogen-derived sediment from the Appalachian and/or Ouachita system and continental-block-derived sediment from paleohighs and uplifts within the Gulf basin. However, Norphlet sandstones plot in the craton-interior and transitional-continental fields on Q-F-L and QM-F-Lt tectonic-provenance diagrams, because of mineralogically mature source rocks, elimination of unstable grains by abrasion and sorting during deposition, and/or sediment mixing from different source terranes.

  3. Securing Provenance of Distributed Processes in an Untrusted Environment

    NASA Astrophysics Data System (ADS)

    Syalim, Amril; Nishide, Takashi; Sakurai, Kouichi

    Recently, there is much concern about the provenance of distributed processes, that is about the documentation of the origin and the processes to produce an object in a distributed system. The provenance has many applications in the forms of medical records, documentation of processes in the computer systems, recording the origin of data in the cloud, and also documentation of human-executed processes. The provenance of distributed processes can be modeled by a directed acyclic graph (DAG) where each node represents an entity, and an edge represents the origin and causal relationship between entities. Without sufficient security mechanisms, the provenance graph suffers from integrity and confidentiality problems, for example changes or deletions of the correct nodes, additions of fake nodes and edges, and unauthorized accesses to the sensitive nodes and edges. In this paper, we propose an integrity mechanism for provenance graph using the digital signature involving three parties: the process executors who are responsible in the nodes' creation, a provenance owner that records the nodes to the provenance store, and a trusted party that we call the Trusted Counter Server (TCS) that records the number of nodes stored by the provenance owner. We show that the mechanism can detect the integrity problem in the provenance graph, namely unauthorized and malicious “authorized” updates even if all the parties, except the TCS, collude to update the provenance. In this scheme, the TCS only needs a very minimal storage (linear with the number of the provenance owners). To protect the confidentiality and for an efficient access control administration, we propose a method to encrypt the provenance graph that allows access by paths and compartments in the provenance graph. We argue that encryption is important as a mechanism to protect the provenance data stored in an untrusted environment. We analyze the security of the integrity mechanism, and perform experiments to measure

  4. Data Provenance Architecture for the Geosciences

    NASA Astrophysics Data System (ADS)

    Murphy, F.; Irving, D. H.

    2012-12-01

    The pace at which geoscientific insights inform societal development quickens with time and these insights drive decisions and actions of ever-increasing human and economic significance. Until recently academic, commercial and government bodies have maintained distinct bodies of knowledge to support scientific enquiry as well as societal development. However, it has become clear that the curation of the body of data is an activity of equal or higher social and commercial value. We address the community challenges in the curation of, access to, and analysis of scientific data including: the tensions between creators, providers and users; incentives and barriers to sharing; ownership and crediting. We also discuss the technical and financial challenges in maximising the return on the effort made in generating geoscientific data. To illustrate how these challenges might be addressed in the broader geoscientific domain, we describe the high-level data governance and analytical architecture in the upstream Oil Industry. This domain is heavily dependent on costly and highly diverse geodatasets collected and assimilated over timeframes varying from seconds to decades. These data must support both operational decisions at the minute-hour timefame and strategic and economic decisions of enterprise or national scale, and yet be sufficiently robust to last the life of a producing field. We develop three themes around data provenance, data ownership and business models for data curation. 1/ The overarching aspiration is to ensure that data provenance and quality is maintained along the analytical workflow. Hence if data on which a publication or report changes, the report and its publishers can be notified and we describe a mechanism by which dependent knowledge products can be flagged. 2/ From a cost and management point of view we look at who "owns" data especially in cases where the cost of curation and stewardship is significant compared to the cost of acquiring the data

  5. Geochemical provenance of Florida basement components

    SciTech Connect

    Heatherington, A.L.; Mueller, P.A. . Dept. of Geology); Dallmeyer, R.D. . Dept. of Geology)

    1993-03-01

    The pre-Cretaceous basement of Florida is generally considered to be exotic with respect to Proterozoic Laurentia. Paleontologic and paleomagnetic evidence have suggested a Gondwanan provenance for the Floridan basement, as either a peri-Gondwanide terrane or as a rifted block of the West African craton. The report of generally similar lithologic sequences and a record of similar Ar-Ar cooling ages in some Floridan and West African lithologic units has led to very specific correlations between these units. U-Pb, Sm-Nd, and Rb-Sr geochronologic studies as well as isotopic and elemental abundance data have been used to evaluate the validity of these correlations. Results indicate: (1) geochemical similarities between volcanic rocks of northeastern Florida and a Pan-African metavolcanic sequence (Niokola-Koba group) exposed in Senegal; (2) an absence of a Grenvillian-age (i.e., Laurentian) component in zircons separated from a Paleozoic Suwanee basin sandstone; and (3) whole-rock Sm-Nd and U-Pb zircon evidence for an Archean ([approximately]3.0 Ga) component in the neo-Proterozoic Osceola granitoid(s). Although silicic rocks from throughout Florida have Nd model ages (T[sub DM]) that are predominantly Grenvillian (1.1--1.4 Ga), the absence of a Grenvillian component in zircons separated from granite and sandstone suggests that the model ages represent a mixture of older and younger components. Overall, the evidence for Birimian ([approximately]2.1 Ga) and Liberian ([approximately]3.0 Ga) age components in the Florida basement are consistent with its origin as a rifted block of cratonic Gondwana. In addition to demonstrating a strong affinity between the Florida basement and cratonic West Africa/northern South America, these data provide a basis for comparison with other circum-Atlantic terranes traditionally described as Avalonian/Cadomian, etc.

  6. Key Provenance of Earth Science Observational Data Products

    NASA Astrophysics Data System (ADS)

    Conover, H.; Plale, B.; Aktas, M.; Ramachandran, R.; Purohit, P.; Jensen, S.; Graves, S. J.

    2011-12-01

    As the sheer volume of data increases, particularly evidenced in the earth and environmental sciences, local arrangements for sharing data need to be replaced with reliable records about the what, who, how, and where of a data set or collection. This is frequently called the provenance of a data set. While observational data processing systems in the earth sciences have a long history of capturing metadata about the processing pipeline, current processes are limited in both what is captured and how it is disseminated to the science community. Provenance capture plays a role in scientific data preservation and stewardship precisely because it can automatically capture and represent a coherent picture of the what, how and who of a particular scientific collection. It reflects the transformations that a data collection underwent prior to its current form and the sequence of tasks that were executed and data products applied to generate a new product. In the NASA-funded Instant Karma project, we examine provenance capture in earth science applications, specifically the Advanced Microwave Scanning Radiometer - Earth Observing System (AMSR-E) Science Investigator-led Processing system (SIPS). The project is integrating the Karma provenance collection and representation tool into the AMSR-E SIPS production environment, with an initial focus on Sea Ice. This presentation will describe capture and representation of provenance that is guided by the Open Provenance Model (OPM). Several things have become clear during the course of the project to date. One is that core OPM entities and relationships are not adequate for expressing the kinds of provenance that is of interest in the science domain. OPM supports name-value pair annotations that can be used to augment what is known about the provenance entities and relationships, but in Karma, annotations cannot be added during capture, but only after the fact. This limits the capture system's ability to record something it

  7. Caring for Women with Inflammatory Bowel Disease.

    PubMed

    Feagins, Linda A; Kane, Sunanda V

    2016-06-01

    Ulcerative colitis and Crohn disease are chronic inflammatory diseases with typical onset in early adulthood. These diseases, therefore, can affect a woman throughout the many stages of her life, including menstruation, sexuality, pregnancy, and menopause. Unique health issues face women during these stages and can affect the course of their inflammatory bowel disease as well as treatment strategies and health maintenance. This article covers the non-pregnancy-related issues that are important in caring for women with inflammatory bowel disease. The topics of pregnancy and fertility are covered in a separate review. PMID:27261900

  8. The provenance of Taklamakan desert sand

    NASA Astrophysics Data System (ADS)

    Rittner, Martin; Vermeesch, Pieter; Carter, Andrew; Bird, Anna; Stevens, Thomas; Garzanti, Eduardo; Andò, Sergio; Vezzoli, Giovanni; Dutt, Ripul; Xu, Zhiwei; Lu, Huayu

    2016-03-01

    Sand migration in the vast Taklamakan desert within the Tarim Basin (Xinjiang Uyghur Autonomous region, PR China) is governed by two competing transport agents: wind and water, which work in diametrically opposed directions. Net aeolian transport is from northeast to south, while fluvial transport occurs from the south to the north and then west to east at the northern rim, due to a gradual northward slope of the underlying topography. We here present the first comprehensive provenance study of Taklamakan desert sand with the aim to characterise the interplay of these two transport mechanisms and their roles in the formation of the sand sea, and to consider the potential of the Tarim Basin as a contributing source to the Chinese Loess Plateau (CLP). Our dataset comprises 39 aeolian and fluvial samples, which were characterised by detrital-zircon U-Pb geochronology, heavy-mineral, and bulk-petrography analyses. Although the inter-sample differences of all three datasets are subtle, a multivariate statistical analysis using multidimensional scaling (MDS) clearly shows that Tarim desert sand is most similar in composition to rivers draining the Kunlun Shan (south) and the Pamirs (west), and is distinctly different from sediment sources in the Tian Shan (north). A small set of samples from the Junggar Basin (north of the Tian Shan) yields different detrital compositions and age spectra than anywhere in the Tarim Basin, indicating that aeolian sediment exchange between the two basins is minimal. Although river transport dominates delivery of sand into the Tarim Basin, wind remobilises and reworks the sediment in the central sand sea. Characteristic signatures of main rivers can be traced from entrance into the basin to the terminus of the Tarim River, and those crossing the desert from the south to north can seasonally bypass sediment through the sand sea. Smaller ephemeral rivers from the Kunlun Shan end in the desert and discharge their sediment there. Both river run

  9. Application of Named Graphs Towards Custom Provenance Views

    SciTech Connect

    Gibson, Tara D.; Schuchardt, Karen L.; Stephan, Eric G.

    2009-02-10

    Provenance capture as applied to execution oriented and interactive workflows is designed to record minute detail needed to support a "modify and restart" paradigm as well as re-execution of past workflows. In our experience, provenance also plays an important role in human-centered verification, results tracking, and knowledge sharing. To enable this we must overcome the low level of detail received from most provenance capture mechanisms and pre-sent it in a user oriented view. In this paper, we present a design which leverages named graphs to create and man-age views as a server-side function, simplifying user presentation of provenance data.

  10. Semantic Workflows and Provenance-Aware Software (Invited)

    NASA Astrophysics Data System (ADS)

    Gil, Y.

    2013-12-01

    Workflows are increasingly used in science to manage complex computations and data processing at large scale. Intelligent workflow systems provide assistance in setting up parameters and data, validating workflows created by users, and automating the generation of workflows from high-level user guidance. These systems use semantic workflows that extend workflow representations with semantic constraints that express characteristics of the data and analytic models. Reasoning algorithms propagate these semantic constraints throughout the workflow structure, select executable components for underspecified steps, and suggest parameter values. Semantic workflows also enhance provenance records with abstract steps that reflect the overall data analysis method rather than just execution traces. Intelligent workflow systems are provenance-aware, since they both use and generate provenance and metadata as the data is being processed. Provenance-aware software enhances scientific analysis by propagating upstream metadata and provenance to new data products. Through the use of provenance standards, such as the recent W3C PROV recommendation for provenance on the Web, provenance-aware software can significantly enhance scientific data analysis, publication, and reuse. New capabilities are enabled when provenance is brought to the forefront in the design of software systems for science.

  11. Towards a common provenance model for research publications

    NASA Astrophysics Data System (ADS)

    Fu, L.; Ma, X.; West, P.; Beaulieu, S. E.; Di Stefano, M.; Fox, P. A.

    2014-12-01

    Provenance is information about entities, activities, and people involved in producing a piece of data or thing, which can be used to form assessments about its quality, reliability or trustworthiness. In a research publication, provenance includes entities, activities and people involved in the process leading to the parts of the publication such as figures, tables, paragraphs etc. Such information is often desirable for the readers to correctly interpret publication content and enables them to evaluate the credibility of the reported results by digging into the software in use, source data and responsible agents or even reproducing the results themselves. In this presentation, we will describe our ontology designed to model the preparing process of research publications based on our experience from two projects, both focusing on provenance capturing for research publications. The first project is about capturing provenance information for a National Climate Assessment (NCA) report of the US Global Change Research Program (USGCRP), and the second about capturing provenance information for an Ecosystem Status Report (ESR) of the Northeast Fisheries Science Center (NEFSC). Both projects base their provenance modeling on the W3C Provenance ontology (PROV-O), which proves to be an effective way to create models for provenance capturing. We will illustrate the commonalities and differences between use cases of these two projects and how we derive a common model from models specifically designed to capture provenance information for each of the projects.

  12. Nestin(+) cells direct inflammatory cell migration in atherosclerosis.

    PubMed

    Del Toro, Raquel; Chèvre, Raphael; Rodríguez, Cristina; Ordóñez, Antonio; Martínez-González, José; Andrés, Vicente; Méndez-Ferrer, Simón

    2016-01-01

    Atherosclerosis is a leading death cause. Endothelial and smooth muscle cells participate in atherogenesis, but it is unclear whether other mesenchymal cells contribute to this process. Bone marrow (BM) nestin(+) cells cooperate with endothelial cells in directing monocyte egress to bloodstream in response to infections. However, it remains unknown whether nestin(+) cells regulate inflammatory cells in chronic inflammatory diseases, such as atherosclerosis. Here, we show that nestin(+) cells direct inflammatory cell migration during chronic inflammation. In Apolipoprotein E (ApoE) knockout mice fed with high-fat diet, BM nestin(+) cells regulate the egress of inflammatory monocytes and neutrophils. In the aorta, nestin(+) stromal cells increase ∼30 times and contribute to the atheroma plaque. Mcp1 deletion in nestin(+) cells-but not in endothelial cells only- increases circulating inflammatory cells, but decreases their aortic infiltration, delaying atheroma plaque formation and aortic valve calcification. Therefore, nestin expression marks cells that regulate inflammatory cell migration during atherosclerosis. PMID:27586429

  13. Inflammatory bowel disease in ankylosing spondylitis

    PubMed Central

    Jayson, M. I. V.; Salmon, P. R.; Harrison, W. J.

    1970-01-01

    Routine detailed gastroenterological investigations were performed in a series of 47 ankylosing spondylitics. Evidence of chronic inflammatory bowel disease was found in eight patients, a prevalence of 17%. Unsuspected bowel disease was found in the absence of symptoms in three of these patients. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5 PMID:5430378

  14. Chronic rhinosinusitis pathogenesis.

    PubMed

    Stevens, Whitney W; Lee, Robert J; Schleimer, Robert P; Cohen, Noam A

    2015-12-01

    There are a variety of medical conditions associated with chronic sinonasal inflammation, including chronic rhinosinusitis (CRS) and cystic fibrosis. In particular, CRS can be divided into 2 major subgroups based on whether nasal polyps are present or absent. Unfortunately, clinical treatment strategies for patients with chronic sinonasal inflammation are limited, in part because the underlying mechanisms contributing to disease pathology are heterogeneous and not entirely known. It is hypothesized that alterations in mucociliary clearance, abnormalities in the sinonasal epithelial cell barrier, and tissue remodeling all contribute to the chronic inflammatory and tissue-deforming processes characteristic of CRS. Additionally, the host innate and adaptive immune responses are also significantly activated and might be involved in pathogenesis. Recent advancements in the understanding of CRS pathogenesis are highlighted in this review, with special focus placed on the roles of epithelial cells and the host immune response in patients with cystic fibrosis, CRS without nasal polyps, or CRS with nasal polyps. PMID:26654193

  15. Inflammatory pathways in spondyloarthritis.

    PubMed

    Hreggvidsdottir, Hulda S; Noordenbos, Troy; Baeten, Dominique L

    2014-01-01

    Spondyloarthritis is the second most common form of chronic inflammatory arthritis and a unique hallmark of the disease is pathologic new bone formation. Several cytokine pathways have been genetically associated with ankylosing spondylitis (AS), the prototypic subtype of SpA, and additional evidence from human and animal studies support a role of these pathways in the disease. TNF has a key role in SpA as blockade significantly reduces inflammation and destruction, however the treatment does not halt new bone formation. New insights into the TNF pathway were recently obtained from an animal model specifically overexpressing the transmembrane form of TNF. This model leads to axial and peripheral new bone formation which is not seen in soluble TNF overexpression models, indicating different pathogenic roles of soluble and transmembrane TNF in arthritis development. Besides TNF, the IL-23/IL-17 axis is emerging as an important inflammatory pathway in SpA, as a SNP in the IL-23R locus has been associated with developing AS, mice overexpressing IL-23 develop SpA-like features and IL-17 blockade has been shown to be efficacious for AS patients in a phase II trial. In this review, we focus on the cytokine pathways that have recently been genetically associated with SpA, i.e. TNF, IL-1, IL-6 and IL-23/IL-17. We review the current genetic, experimental and human in vivo data available and discuss how these different pathways are involved in the pathophysiology of SpA. Additionally, we discuss how these pathways relate to the pathogenic new bone formation in SpA. PMID:23969080

  16. Autoantibodies in inflammatory arthritis.

    PubMed

    Conigliaro, P; Chimenti, M S; Triggianese, P; Sunzini, F; Novelli, L; Perricone, C; Perricone, R

    2016-07-01

    Rheumatoid arthritis (RA) is a systemic chronic inflammatory disease characterized by extensive synovitis resulting in erosions of articular cartilage and marginal bone with joint destruction. The lack of immunological tolerance in RA represents the first step toward the development of autoimmunity. Susceptible individuals, under the influence of environmental factors, such as tobacco smoke, and silica exposure, develop autoimmune phenomena that result in the presence of autoantibodies. HLA and non-HLA haplotypes play a major role in determining the development of specific autoantibodies differentiating anti-citrullinated antibodies (ACPA)-positive and negative RA patients. Rheumatoid factor (RF) and ACPA are the serological markers for RA, and during the preclinical immunological phase, autoantibody titers increase with a progressive spread of ACPA antigens repertoire. The presence of ACPA represents an independent risk factor for developing RA in patients with undifferentiated arthritis or arthralgia. Moreover, anti-CarP antibodies have been identified in patients with RA as well as in individuals before the onset of clinical symptoms of RA. Several autoantibodies mainly targeting post-translational modified proteins have been investigated as possible biomarkers to improve the early diagnosis, prognosis and response to therapy in RA patients. Psoriatic arthritis (PsA) is distinguished from RA by infrequent positivity for RF and ACPA, together with other distinctive clinical features. Actually, specific autoantibodies have not been described. Recently, anti-CarP antibodies have been reported in sera from PsA patients with active disease. Further investigations on autoantibodies showing high specificity and sensibility as well as relevant correlation with disease severity, progression, and response to therapy are awaited in inflammatory arthritides. PMID:26970491

  17. Impact of concomitant low-dose aspirin on the safety and tolerability of naproxen and esomeprazole magnesium delayed-release tablets in patients requiring chronic nonsteroidal anti-inflammatory drug therapy: an analysis from 5 Phase III studies.

    PubMed

    Angiolillo, Dominick J; Datto, Catherine; Raines, Shane; Yeomans, Neville D

    2014-07-01

    Patients receiving chronic nonsteroidal anti-inflammatory drugs (NSAIDs) and concomitant low-dose aspirin (LDA) are at increased risk of gastrointestinal (GI) toxicity. A fixed-dose combination of enteric-coated (EC) naproxen and immediate-release esomeprazole magnesium (NAP/ESO) has been designed to deliver a proton-pump inhibitor followed by an NSAID in a single tablet. To examine safety data from 5 Phase III studies of NAP/ESO in LDA users (≤ 325 mg daily, administered at any time during the study), and LDA non-users, data were analyzed from 6-month studies assessing NAP/ESO versus EC naproxen in patients with osteoarthritis, rheumatoid arthritis, or ankylosing spondylitis (n = 2), 3-month studies assessing NAP/ESO vs celecoxib or placebo in patients with knee osteoarthritis (n = 2), and a 12-month, open-label, safety study of NAP/ESO (n = 1). In an analysis of two studies, incidences of endoscopically confirmed gastric ulcers (GUs) and duodenal ulcers (DUs) were summarized by LDA subgroups. In the pooled analysis from all five studies, incidences of treatment-emergent adverse events (AEs) (including prespecified NSAID-associated upper GI AEs and cardiovascular AEs), serious AEs, and AE-related discontinuations were stratified by LDA subgroups. Overall, 2,317 patients received treatment; 1,157 patients received NAP/ESO and, of these, 298 received LDA. The cumulative incidence of GUs and DUs in the two studies with 6-month follow-up was lower for NAP/ESO vs EC naproxen in both LDA subgroups [GUs: 3.0 vs 27.9%, respectively, for LDA users, 6.4 vs 22.4%, respectively, for LDA non-users (both P < 0.001); DUs: 1.0 vs 5.8% for LDA users, 0.6 vs 5.3% for LDA non-users]. The incidence of erosive gastritis was lower in NAP/ESO- vs EC naproxen-treated patients for both LDA users [18.2 vs 36.5%, respectively (P = 0.004)] and LDA non-users [19.8 vs 38.5%, respectively (P < 0.001)]. Among LDA users, incidences of NSAID-associated upper GI AEs were: NAP/ESO, 16.1%; EC

  18. [Chronic migraine: treatment].

    PubMed

    Pascual, Julio

    2012-04-10

    We define chronic migraine as that clinical situation in which migraine attacks appear 15 or more days per month. Until recently, and in spite of its negative impact, patients with chronic migraine were excluded of the clinical trials. This manuscript revises the current treatment of chronic migraine. The first step should include the avoidance of potential precipitating/aggravating factors for chronic migraine, mainly analgesic overuse and the treatment of comorbid disorders, such as anxiety and depression. The symptomatic treatment should be based on the use of nonsteroidal anti-inflammatory agents and triptans (in this case < 10 days per month). It is necessary to avoid the use of combined analgesics, opioids and ergotamine-containing medications. Preventive treatment includes a 'transitional' treatment with nonsteroidal anti-inflammatory agents or steroids, while preventive treatment exerts its actions. Even though those medications efficacious in episodic migraine prevention are used, the only drugs with demonstrated efficacy in the preventive treatment of chronic migraine are topiramate and pericranial infiltrations of Onabotulinumtoxin A. PMID:22532241

  19. Inflammatory Mechanisms in Hidradenitis Suppurativa.

    PubMed

    Kelly, G; Prens, Errol P

    2016-01-01

    Hidradenitis suppurativa (HS) is a chronic relapsing disease of follicular occlusion that causes immense clinical and psychosocial morbidity when refractory to treatment. HS is no longer considered a disease of primary infectious etiology, although bacteria play a role. There is increasing evidence that HS is associated with immune dysregulation, based on its clinical association with other immune-mediated disorders, by its response to biologic therapy in the clinical arena, and from molecular research. This article summarizes what is known in relation to the inflammatory pathways in HS. PMID:26617358

  20. Inflammatory demyelinating neuropathies.

    PubMed

    Muley, Suraj Ashok; Parry, Gareth J

    2009-05-01

    Early and effective treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) is important to minimize axonal degeneration that occurs secondary to demyelination. The disease course is invariably chronic, so long-term treatment is often required, and adverse effects and costs are important considerations in devising a treatment plan. CIDP responds to prednisone, but long-term treatment can result in significant adverse effects. Azathioprine, mycophenolate mofetil, and cyclosporine can be used as steroid-sparing agents and may facilitate more rapid and successful tapering of prednisone. Intravenous immunoglobulin (IVIg) and plasma exchange are also effective in the treatment of CIDP and can be used in patients who are unresponsive to prednisone or develop steroid-related adverse effects. IVIg may also be used as a first-line treatment, but its cost can be a limiting factor. A few uncontrolled studies have suggested that pulsed weekly methylprednisolone is both effective and well tolerated in the long-term treatment of CIDP. Treatments based on rituximab or cyclophosphamide have also been used in resistant disease. Variants of CIDP have been described on the basis of their association with specific antibodies or immunoglobulins and their response to specific immunomodulatory treatments. Multifocal motor neuropathy with conduction block responds to IVIg in the majority of patients. However, weakness may slowly worsen over time, and some patients become unresponsive. Anecdotal reports suggest that rituximab may be useful in patients who develop progressive disease. Placebo-controlled trials in anti-myelin-associated glycoprotein neuropathy suggest that rituximab is effective and, with a combination of prednisone and cyclophosphamide, numbness and strength may improve. Other treatments that may be effective include plasma exchange and IVIg. Treatment is generally started with prednisone, IVIg, or plasma exchange. Rituximab and cyclophosphamide are used only

  1. Chronic gastrointestinal haemorrhage controlled by antifibrinolytic agents.

    PubMed Central

    Willoughby, J. M.

    1989-01-01

    Antifibrinolytic agents are used chiefly for control of acute haemorrhage. Their applicability to chronic bleeding from inflammatory lesions of the gastrointestinal tract is illustrated by two case histories. PMID:2813242

  2. Angiogenesis in Inflammatory Bowel Disease

    PubMed Central

    Alkim, Canan; Alkim, Huseyin; Koksal, Ali Riza; Boga, Salih; Sen, Ilker

    2015-01-01

    Angiogenesis is an important component of pathogenesis of inflammatory bowel disease (IBD). Chronic inflammation and angiogenesis are two closely related processes. Chronic intestinal inflammation is dependent on angiogenesis and this angiogenesis is modulated by immune system in IBD. Angiogenesis is a very complex process which includes multiple cell types, growth factors, cytokines, adhesion molecules, and signal transduction. Lymphangiogenesis is a new research area in the pathogenesis of IBD. While angiogenesis supports inflammation via leukocyte migration, carrying oxygen and nutrients, on the other hand, it has a major role in wound healing. Angiogenic molecules look like perfect targets for the treatment of IBD, but they have risk for serious side effects because of their nature. PMID:26839731

  3. The importance of balanced pro-inflammatory and anti-inflammatory mechanisms in diffuse lung disease

    PubMed Central

    Keane, Michael P; Strieter, Robert M

    2002-01-01

    The lung responds to a variety of insults in a remarkably consistent fashion but with inconsistent outcomes that vary from complete resolution and return to normal to the destruction of normal architecture and progressive fibrosis. Increasing evidence indicates that diffuse lung disease results from an imbalance between the pro-inflammatory and anti-inflammatory mechanisms, with a persistent imbalance that favors pro-inflammatory mediators dictating the development of chronic diffuse lung disease. This review focuses on the mediators that influence this imbalance. PMID:11806840

  4. [Pauciarticular juvenile chronic arthritis].

    PubMed

    Hertzberger-ten Cate, R; Fiselier, T

    1991-10-01

    On basis of clinical and immunogenetic factors most children with pauciarticular juvenile chronic arthritis can be included in one of the subtypes: type 1 and type 2 pauciarticular JCA. Type 1 occurs in young children, mainly girls, with involvement of knees, ankles or elbows. In the majority of children antinuclear antibodies can be detected. The presence of these autoantibodies is associated with chronic anterior uveitis. Type 2 or the juvenile spondylarthropathies include morbus Bechterew, the reactive arthritides and arthritis associated with psoriasis and inflammatory bowel diseases. Large joints of the lower extremities are involved, back pain is unusual at onset, but enthesitis is frequently present. There is a strong association with HLA-B27. Treatment of both subsets consists of non-steroidal anti-inflammatory drugs, application of intra-articular steroids, physio- and hydrotherapy and splinting. In children with a polyarticular course of type 1, or a prolonged course of type 2 disease modifying drugs are often needed. PMID:1957301

  5. SEIS-PROV: Practical Provenance for Seismological Data

    NASA Astrophysics Data System (ADS)

    Krischer, L.; Smith, J. A.; Tromp, J.

    2015-12-01

    It is widely recognized that reproducibility is crucial to advance science, but at the same time it is very hard to actually achieve. This results in it being recognized but also mostly ignored by a large fraction of the community. A key ingredient towards full reproducibility is to capture and describe the history of data, an issue known as provenance. We present SEIS-PROV, a practical format and data model to store provenance information for seismological data. In a seismological context, provenance can be seen as information about the processes that generated and modified a particular piece of data. For synthetic waveforms the provenance information describes which solver and settings therein were used to generate it. When looking at processed seismograms, the provenance conveys information about the different time series analysis steps that led to it. Additional uses include the description of derived data types, such as cross-correlations and adjoint sources, enabling their proper storage and exchange. SEIS-PROV is based on W3C PROV (http://www.w3.org/TR/prov-overview/), a standard for generic provenance information. It then applies an additional set of constraints to make it suitable for seismology. We present a definition of the SEIS-PROV format, a way to check if any given file is a valid SEIS-PROV document, and two sample implementations: One in SPECFEM3D GLOBE (https://geodynamics.org/cig/software/specfem3d_globe/) to store the provenance information of synthetic seismograms and another one as part of the ObsPy (http://obspy.org) framework enabling automatic tracking of provenance information during a series of analysis and transformation stages. This, along with tools to visualize and interpret provenance graphs, offers a description of data history that can be readily tracked, stored, and exchanged.

  6. Surgical Approaches to Chronic Pancreatitis

    PubMed Central

    Hartmann, Daniel; Friess, Helmut

    2015-01-01

    Chronic pancreatitis is a progressive inflammatory disease resulting in permanent structural damage of the pancreas. It is mainly characterized by recurring epigastric pain and pancreatic insufficiency. In addition, progression of the disease might lead to additional complications, such as pseudocyst formation or development of pancreatic cancer. The medical and surgical treatment of chronic pancreatitis has changed significantly in the past decades. With regard to surgical management, pancreatic head resection has been shown to be a mainstay in the treatment of severe chronic pancreatitis because the pancreatic head mass is known to trigger the chronic inflammatory process. Over the years, organ-preserving procedures, such as the duodenum-preserving pancreatic head resection and the pylorus-preserving Whipple, have become the surgical standard and have led to major improvements in pain relief, preservation of pancreatic function, and quality of life of patients. PMID:26681935

  7. Anti-inflammatory and immunomodulatory properties of Carica papaya.

    PubMed

    Pandey, Saurabh; Cabot, Peter J; Shaw, P Nicholas; Hewavitharana, Amitha K

    2016-07-01

    Chronic inflammation is linked with the generation and progression of various diseases such as cancer, diabetes and atherosclerosis, and anti-inflammatory drugs therefore have the potential to assist in the treatment of these conditions. Carica papaya is a tropical plant that is traditionally used in the treatment of various ailments including inflammatory conditions. A literature search was conducted by using the keywords "papaya", "anti-inflammatory and inflammation" and "immunomodulation and immune" along with cross-referencing. Both in vitro and in vivo investigation studies were included. This is a review of all studies published since 2000 on the anti-inflammatory activity of papaya extracts and their effects on various immune-inflammatory mediators. Studies on the anti-inflammatory activities of recognized phytochemicals present in papaya are also included. Although in vitro and in vivo studies have shown that papaya extracts and papaya-associated phytochemicals possess anti-inflammatory and immunomodulatory properties, clinical studies are lacking. PMID:27416522

  8. Inflammatory bowel disease: Pathogenesis

    PubMed Central

    Zhang, Yi-Zhen; Li, Yong-Yu

    2014-01-01

    Inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, is characterized by chronic relapsing intestinal inflammation. It has been a worldwide health-care problem with a continually increasing incidence. It is thought that IBD results from an aberrant and continuing immune response to the microbes in the gut, catalyzed by the genetic susceptibility of the individual. Although the etiology of IBD remains largely unknown, it involves a complex interaction between the genetic, environmental or microbial factors and the immune responses. Of the four components of IBD pathogenesis, most rapid progress has been made in the genetic study of gut inflammation. The latest internationally collaborative studies have ascertained 163 susceptibility gene loci for IBD. The genes implicated in childhood-onset and adult-onset IBD overlap, suggesting similar genetic predispositions. However, the fact that genetic factors account for only a portion of overall disease variance indicates that microbial and environmental factors may interact with genetic elements in the pathogenesis of IBD. Meanwhile, the adaptive immune response has been classically considered to play a major role in the pathogenesis of IBD, as new studies in immunology and genetics have clarified that the innate immune response maintains the same importance in inducing gut inflammation. Recent progress in understanding IBD pathogenesis sheds lights on relevant disease mechanisms, including the innate and adaptive immunity, and the interactions between genetic factors and microbial and environmental cues. In this review, we provide an update on the major advances that have occurred in above areas. PMID:24415861

  9. Is Synovial Macrophage Activation the Inflammatory Link Between Obesity and Osteoarthritis?

    PubMed

    Sun, Antonia RuJia; Friis, Thor; Sekar, Sunderajhan; Crawford, Ross; Xiao, Yin; Prasadam, Indira

    2016-09-01

    Osteoarthritis (OA) is the most common musculoskeletal disease, affecting nearly 25 % of the world population (WHO reports), leading to pain and disability. There are as yet no clinically proven therapies to halt OA onset or progression; the development of such therapies is, therefore, a national as well as international research priority. Obesity-related metabolic syndrome has been identified as the most significant, but also an entirely preventable risk factor for OA; however, the mechanisms underlying this link remain unclear. We have examined the available literature linking OA and metabolic syndrome. The two conditions have a shared pathogenesis in which chronic low-grade inflammation of affected tissues is recognized as a major factor that is associated with systemic inflammation. In addition, the occurrence of metabolic syndrome appears to alter systemic and local pro-inflammatory cytokines that are also related to the development of OA-like pathologies. Recent findings highlight the importance not only of the elevated number of macrophage in inflamed synovium but also the activation and amplification of the inflammatory state and other pathological changes. The role of local inflammation on the synovium is now considered to be a pharmacological target against which to aim disease-modifying drugs. In this review, we evaluate evidence linking OA, synovitis and metabolic syndrome and discuss the merits of targeting macrophage activation as a valid treatment option for OA. PMID:27422277

  10. The Symbiotic Relationship between Scientific Workflow and Provenance (Invited)

    NASA Astrophysics Data System (ADS)

    Stephan, E.

    2010-12-01

    The purpose of this presentation is to describe the symbiotic nature of scientific workflows and provenance. We will also discuss the current trends and real world challenges facing these two distinct research areas. Although motivated differently, the needs of the international science communities are the glue that binds this relationship together. Understanding and articulating the science drivers to these communities is paramount as these technologies evolve and mature. Originally conceived for managing business processes, workflows are now becoming invaluable assets in both computational and experimental sciences. These reconfigurable, automated systems provide essential technology to perform complex analyses by coupling together geographically distributed disparate data sources and applications. As a result, workflows are capable of higher throughput in a shorter amount of time than performing the steps manually. Today many different workflow products exist; these could include Kepler and Taverna or similar products like MeDICI, developed at PNNL, that are standardized on the Business Process Execution Language (BPEL). Provenance, originating from the French term Provenir “to come from”, is used to describe the curation process of artwork as art is passed from owner to owner. The concept of provenance was adopted by digital libraries as a means to track the lineage of documents while standards such as the DublinCore began to emerge. In recent years the systems science community has increasingly expressed the need to expand the concept of provenance to formally articulate the history of scientific data. Communities such as the International Provenance and Annotation Workshop (IPAW) have formalized a provenance data model. The Open Provenance Model, and the W3C is hosting a provenance incubator group featuring the Proof Markup Language. Although both workflows and provenance have risen from different communities and operate independently, their mutual

  11. PROVEN ALTERNATIVES FOR ABOVEGROUND TREATMENT OF ARSENIC IN GROUNDWATER

    EPA Science Inventory

    This report was prepared as an issue paper for the EPA Engineering Forum, summarizes experiences with proven aboveground treatment alternatives for arsenic in groundwater, and provides information on their relative performance and cost. The four technologies reviewed are: preci...

  12. Gene expression profiling of inflammatory bladder disorders.

    PubMed

    Saban, Marcia R; Nguyen, Ngoc-Bich; Hurst, Robert E; Saban, Ricardo

    2003-03-01

    Inflammation underlies all major bladder pathologies including malignancy and represents a defense reaction to injury caused by physical damage, chemical substances, micro-organisms or other agents. During acute inflammation, activation of specific molecular pathways leads to an increased expression of selected genes whose products attack the insult, but ultimately should protect the tissue from the noxious stimulus. However, once the stimulus ceases, gene-expression should return to basal levels to avoid tissue damage, fibrosis, loss of function, and chronic inflammation. If this down-regulation does not occur, tissue fibrosis occurs as a serious complication of chronic inflammation. Although sensory nerve and most cells products are known to be key parts of the inflammatory puzzle, other key molecules are constantly being described that have a role in bladder inflammation. Therefore, as the database describing the repertoire of inflammatory mediators implicated in bladder inflammation increases, the central mechanisms by which injury can induce inflammation, cell damage, and repair often becomes less rather than more clear. To make sense of the vast knowledge of the genes involved in the inflammatory response may require analysis of the patterns of change and the elucidation of gene networks far more than definition of additional members of inflammatory cascades. This review discuss the appropriate use of microarray technology, which promises to solve both of these problems as well as identifying key molecules and mechanisms involved in the transition between acute and chronic inflammation. PMID:12647997

  13. Restful Implementation of Catalogue Service for Geospatial Data Provenance

    NASA Astrophysics Data System (ADS)

    Jiang, L. C.; Yue, P.; Lu, X. C.

    2013-10-01

    Provenance, also known as lineage, is important in understanding the derivation history of data products. Geospatial data provenance helps data consumers to evaluate the quality and reliability of geospatial data. In a service-oriented environment, where data are often consumed or produced by distributed services, provenance could be managed by following the same service-oriented paradigm. The Open Geospatial Consortium (OGC) Catalogue Service for the Web (CSW) is used for the registration and query of geospatial data provenance by extending ebXML Registry Information Model (ebRIM). Recent advance of the REpresentational State Transfer (REST) paradigm has shown great promise for the easy integration of distributed resources. RESTful Web Service aims to provide a standard way for Web clients to communicate with servers based on REST principles. The existing approach for provenance catalogue service could be improved by adopting the RESTful design. This paper presents the design and implementation of a catalogue service for geospatial data provenance following RESTful architecture style. A middleware named REST Converter is added on the top of the legacy catalogue service to support a RESTful style interface. The REST Converter is composed of a resource request dispatcher and six resource handlers. A prototype service is developed to demonstrate the applicability of the approach.

  14. Automatic run-time provenance capture for scientific dataset generation

    NASA Astrophysics Data System (ADS)

    Frew, J.; Slaughter, P.

    2008-12-01

    Provenance---the directed graph of a dataset's processing history---is difficult to capture effectively. Human- generated provenance, as narrative metadata, is labor-intensive and thus often incorrect, incomplete, or simply not recorded. Workflow systems capture some provenance implicitly in workflow specifications, but these systems are not ubiquitous or standardized, and a workflow specification may not capture all of the factors involved in a dataset's production. System audit trails capture potentially all processing activities, but not the relationships between them. We describe a system that transparently (i.e., without any modification to science codes) and automatically (i.e. without any human intervention) captures the low-level interactions (files read/written, parameters accessed, etc.) between scientific processes, and then synthesizes these relationships into a provenance graph. This system---the Earth System Science Server (ES3)---is sufficiently general that it can accommodate any combination of stand-alone programs, interpreted codes (e.g. IDL), and command- language scripts. Provenance in ES3 can be published in well-defined XML formats (including formats suitable for graphical visualization), and queried to determine the ancestors or descendants of any specific data file or process invocation. We demonstrate how ES3 can be used to capture the provenance of a large operational ocean color dataset.

  15. [Progress in PDE4 targeted therapy for inflammatory diseases].

    PubMed

    Song, Shun-de; Tang, Hui-fang

    2014-05-01

    cAMP-specific phosphodiesterase type 4 (PDE4) is one of the hot targets for treatment of inflammatory diseases. PDE4 inhibitors can suppress inflammation by increasing the concentration of cAMP in inflammatory cells. The efficacy and safety evaluations of several PDE4 inhibitors are currently carried on in clinical trials, for example GSK256066 in asthma, roflumilast and GSK256066 in chronic obstructive pulmonary disease, tetomilast in inflammatory bowel disease, and apremilast in dermatitis and arthritis etc. This article reviews the recent progress on PDE4-targeted therapy for inflammatory diseases. PMID:24998661

  16. Provenance in Data Interoperability for Multi-Sensor Intercomparison

    NASA Astrophysics Data System (ADS)

    Lynnes, C.; Leptoukh, G.; Berrick, S.; Shen, S.; Prados, A.; Fox, P.; Yang, W.; Min, M.; Holloway, D.; Enloe, Y.

    2008-12-01

    As our inventory of Earth science data sets grows, the ability to compare, merge and fuse multiple datasets grows in importance. This implies a need for deeper data interoperability than we have now. Many efforts (e.g. OPeNDAP, Open Geospatial Consortium) have broken down format barriers to interoperability; the next challenge is the semantic aspects of the data. Consider the issues when satellite data are merged, cross- calibrated, validated, inter-compared and fused. We must determine how to match up data sets that are related, yet different in significant ways: the exact nature of the phenomenon being measured, measurement technique, exact location in space-time, or the quality of the measurements. If subtle distinctions between similar measurements are not clear to the user, the results can be meaningless or even lead to an incorrect interpretation of the data. Most of these distinctions trace back to how the data came to be: sensors, processing, and quality assessment. For example, monthly averages of satellite-based aerosol measurements often show significant discrepancies, which might be due to differences in spatio-temporal aggregation, sampling issues, sensor biases, algorithm differences and/or calibration issues. This provenance information must therefore be captured in a semantic framework that allows sophisticated data inter-use tools to incorporate it, and eventually aid in the interpretation of comparison or merged products. Semantic web technology allows us to encode our knowledge of measurement characteristics, phenomena measured, space-time representations, and data quality representation in a well-structured, machine- readable ontology and rulesets. An analysis tool can use this knowledge to show users the provenance- related distinctions between two variables, advising on options for further data processing and analysis. An additional problem for workflows distributed across heterogeneous systems is retrieval and transport of provenance

  17. Fibrocytes: emerging effector cells in chronic inflammation

    PubMed Central

    Reilkoff, Ronald A.; Bucala, Richard; Herzog, Erica L.

    2013-01-01

    Fibrocytes are mesenchymal cells that arise from monocyte precursors. They are present in injured organs and have both the inflammatory features of macrophages and the tissue remodelling properties of fibroblasts. Chronic inflammatory stimuli mediate the differentiation, trafficking and accumulation of these cells in fibrosing conditions associated with autoimmunity, cardiovascular disease and asthma. This Opinion article discusses the immunological mediators controlling fibrocyte differentiation and recruitment, describes the association of fibrocytes with chronic inflammatory diseases and compares the potential roles of fibrocytes in these disorders with those of macrophages and fibroblasts. It is hoped that this information prompts new opportunities for the study of these unique cells. PMID:21597472

  18. Enhanced Analgesic Properties and Reduced Ulcerogenic Effect of a Mononuclear Copper(II) Complex with Fenoprofen in Comparison to the Parent Drug: Promising Insights in the Treatment of Chronic Inflammatory Diseases

    PubMed Central

    Gumilar, Fernanda; Boeris, Mónica; Toso, Ricardo; Minetti, Alejandra

    2014-01-01

    Analgesic and ulcerogenic properties have been studied for the copper(II) coordination complex of the nonsteroidal anti-inflammatory drug Fenoprofen and imidazole [Cu(fen)2(im)2] (Cu: copper(II) ion; fen: fenoprofenate anion from Fenoprofen, im: imidazole). A therapeutic dose of 28 mg/kg was tested for [Cu(fen)2(im)2] and 21 mg/kg was employed for Fenoprofen calcium, administered by oral gavage in female mice to compare the therapeutic properties of the new entity. The acetic acid induced writhing test was employed to study visceral pain. The percentage of inhibition in writhing and stretching was 78.9% and 46.2% for the [Cu(fen)2(im)2] and Fenoprofen calcium, respectively. This result indicates that the complex could be more effective in diminishing visceral pain. The formalin test was evaluated to study the impact of the drugs over nociceptive and inflammatory pain. The complex is a more potent analgesic on inflammatory pain than the parent drug. Ulcerogenic effects were evaluated using a model of gastric lesions induced by hypothermic-restraint stress. Fenoprofen calcium salt caused an ulcer index of about 79 mm2 while the one caused by [Cu(fen)2(im)2] was 22 mm2. The complex diminished the development of gastric mucosal ulcers in comparison to the uncomplexed drug. Possible mechanisms of action related to both therapeutic properties have been discussed. PMID:25050353

  19. History of Chronic Subdural Hematoma.

    PubMed

    Lee, Kyeong-Seok

    2015-10-01

    Trephination or trepanation is an intentional surgical procedure performed from the Stone Age. It looks like escaping a black evil from the head. This technique is still used for treatment of chronic subdural hematoma (SDH). Now, we know the origin, pathogenesis and natural history of this lesion. The author try to explore the history of trephination and modern discovery of chronic SDH. The author performed a detailed electronic search of PubMed. By the key word of chronic SDH, 2,593 articles were found without language restriction in May 2015. The author reviewed the fact and way, discovering the present knowledge on the chronic SDH. The first authentic report of chronic SDH was that of Wepfer in 1657. Chronic SDH was regarded as a stroke in 17th century. It was changed as an inflammatory disease in 19th century by Virchow, and became a traumatic lesion in 20th century. However, trauma is not necessary in many cases of chronic SDHs. The more important prerequisite is sufficient potential subdural space, degeneration of the brain. Modifying Virchow's description, chronic SDH is sometimes traumatic, but most often caused by severe degeneration of the brain. From Wepfer's first description, nearly 350 years passed to explore the origin, pathogenesis, and fate of chronic SDH. The nature of the black evil in the head of the Stone Age is uncovering by many authors riding the giant's shoulder. Chronic SDH should be categorized as a degenerative lesion instead of a traumatic lesion. PMID:27169062

  20. History of Chronic Subdural Hematoma

    PubMed Central

    2015-01-01

    Trephination or trepanation is an intentional surgical procedure performed from the Stone Age. It looks like escaping a black evil from the head. This technique is still used for treatment of chronic subdural hematoma (SDH). Now, we know the origin, pathogenesis and natural history of this lesion. The author try to explore the history of trephination and modern discovery of chronic SDH. The author performed a detailed electronic search of PubMed. By the key word of chronic SDH, 2,593 articles were found without language restriction in May 2015. The author reviewed the fact and way, discovering the present knowledge on the chronic SDH. The first authentic report of chronic SDH was that of Wepfer in 1657. Chronic SDH was regarded as a stroke in 17th century. It was changed as an inflammatory disease in 19th century by Virchow, and became a traumatic lesion in 20th century. However, trauma is not necessary in many cases of chronic SDHs. The more important prerequisite is sufficient potential subdural space, degeneration of the brain. Modifying Virchow's description, chronic SDH is sometimes traumatic, but most often caused by severe degeneration of the brain. From Wepfer's first description, nearly 350 years passed to explore the origin, pathogenesis, and fate of chronic SDH. The nature of the black evil in the head of the Stone Age is uncovering by many authors riding the giant's shoulder. Chronic SDH should be categorized as a degenerative lesion instead of a traumatic lesion. PMID:27169062

  1. ISO TC211 standards on Provenance for Earth science

    NASA Astrophysics Data System (ADS)

    Di, L.; Deng, M.

    2014-12-01

    Data provenance, also called lineage, records the derivation history of a data product. The history could include the algorithms used, the process steps taken, the computing environment run, data sources input to the processes, the organization/person responsible for the product, etc. Provenance provides important information to data users for them to determine the usability and reliability of the product. In the science domain, the data provenance is especially important since scientists need to use the information to determine the scientific validity of a data product and to decide if such a product can be used as the basis for further scientific analysis. Provenance is a kind of metadata. In Earth science domain, the International Organization for Standardization (ISO) Technical Committee 211 (ISO TC 211) have set geospatial metadata standards for geospatial data, including ISO 19115:2003-Metadata, ISO 19115-2:2009-Metadata-Part 2: Extensions for imagery and gridded data, and ISO 19115-1:2014 - Metadata -- Part 1: Fundamentals. ISO 19115 and ISO 19115-1 define the fundamental metadata for documenting geospatial data products, and ISO 19115-2 provides additional metadata classes for imagery and gridded data. ISO 19115-1:2014 is the revised version of ISO 19115:2003. ISO 19115 and ISO 19115-1 define fundamental lineage information classes and subclasses. They miss some key information classes needed for documenting the provenance in the Web service environment, such as the running environment, the algorithms, and software executables. However, ISO 19115-2 extends the lineage model in ISO 19115 and provides additional metadata classes needed for documenting provenance information. The combination of lineage models in ISO 19115 and ISO 19115-2 provides a comprehensive provenance information model needed for the web service environment. Currently the ISO Provence standard is not compatible with W3C Prov standard. The revision of ISO 19115-2 will be started in

  2. Chronic Pancreatitis and Neoplasia: Correlation or Coincidence

    PubMed Central

    Bean, A. G.; Bowles, M.; Williamson, R. C. N.

    1997-01-01

    Any link between pancreatic carcinoma and chronic pancreatitis could reflect the malignant potential of a chronic inflammatory process. Four patients with ductal adenocarcinomas had a long history of pancreatic pain (median duration 5 years) and showed clearcut evidence of chronic pancreatitis “downstream” of the tumour. Four were alcoholics and two heavy smokers. These four cases arose within a surgical series of approximately 250 patients with chronic pancreatitis, giving an incidence of 1.6 per cent. The incidence and anatomical distribution of carcinoma and chronic pancreatitis could possibly be consistent with a casual relationship. PMID:9184877

  3. Computational provenance in hydrologic science: a snow mapping example.

    PubMed

    Dozier, Jeff; Frew, James

    2009-03-13

    Computational provenance--a record of the antecedents and processing history of digital information--is key to properly documenting computer-based scientific research. To support investigations in hydrologic science, we produce the daily fractional snow-covered area from NASA's moderate-resolution imaging spectroradiometer (MODIS). From the MODIS reflectance data in seven wavelengths, we estimate the fraction of each 500 m pixel that snow covers. The daily products have data gaps and errors because of cloud cover and sensor viewing geometry, so we interpolate and smooth to produce our best estimate of the daily snow cover. To manage the data, we have developed the Earth System Science Server (ES3), a software environment for data-intensive Earth science, with unique capabilities for automatically and transparently capturing and managing the provenance of arbitrary computations. Transparent acquisition avoids the scientists having to express their computations in specific languages or schemas in order for provenance to be acquired and maintained. ES3 models provenance as relationships between processes and their input and output files. It is particularly suited to capturing the provenance of an evolving algorithm whose components span multiple languages and execution environments. PMID:19087938

  4. Provenance Usage in the OceanLink Project

    NASA Astrophysics Data System (ADS)

    Narock, T.; Arko, R. A.; Carbotte, S. M.; Chandler, C. L.; Cheatham, M.; Fils, D.; Finin, T.; Hitzler, P.; Janowicz, K.; Jones, M.; Krisnadhi, A.; Lehnert, K. A.; Mickle, A.; Raymond, L. M.; Schildhauer, M.; Shepherd, A.; Wiebe, P. H.

    2014-12-01

    A wide spectrum of maturing methods and tools, collectively characterized as the Semantic Web, is helping to vastly improve thedissemination of scientific research. The OceanLink project, an NSF EarthCube Building Block, is utilizing semantic technologies tointegrate geoscience data repositories, library holdings, conference abstracts, and funded research awards. Provenance is a vital componentin meeting both the scientific and engineering requirements of OceanLink. Provenance plays a key role in justification and understanding when presenting users with results aggregated from multiple sources. In the engineering sense, provenance enables the identification of new data and the ability to determine which data sources to query. Additionally, OceanLink will leverage human and machine computation for crowdsourcing, text mining, and co-reference resolution. The results of these computations, and their associated provenance, will be folded back into the constituent systems to continually enhance precision and utility. We will touch on the various roles provenance is playing in OceanLink as well as present our use of the PROV Ontology and associated Ontology Design Patterns.

  5. [Inflammatory mechanisms in nasal polyposis].

    PubMed

    Perić, Aleksandar; Vojvodić, Danilo

    2014-01-01

    Nasal polyposis is a chronic inflammatory disease of the nasal and paranasal sinuses mucosa, characterized by prolapse of edematous mucosa, most commonly from the area of anterior ethmoid. The mean histological characteristics are proliferation of pseudostratified respiratory epithelium, thickening of the basement membrane, focal fibrosis and eosinophilic and lymphocytic infiltration of the lamina propria. Although etiology is unknown, two hypotheses are dominant among the scientists: "hypothesis of staphylococcal superantigens" and "hypothesis of immune barrier dysfunction". Although we have not yet achieved a full understanding of the precise mechanisms underlying the pathogenesis of this disease, it is known that nasal polyposis is associated with intensive chronic inflammation, followed by dysregulation of chemotaxis, migration, activation and function of eosinophils. A great number of cytokines, chemokines, and adhesion molecules are involved in the regulation of these complex mechanisms. After activation, eosinophils produce and release enzymes, which can lead to the damage of mucosa and tissue remodeling. Hyperactive eosinophils release a new amount of chemokines and cytokines, attracting new eosinophils into the site of inflammation, and may cause the persistence of chronic inflammation. PMID:25731009

  6. Inflammatory Choroidal Neovascularization

    PubMed Central

    Neri, Piergiorgi; Lettieri, Marta; Fortuna, Cinzia; Manoni, Mara; Giovannini, Alfonso

    2009-01-01

    Purpose and Methods: Choroidal neovascularization (CNV) can be a severe sight-threatening sequela, which can be secondary to both infectious and noninfectious uveitis. This review summarizes the different diseases associated with CNV, highlighting new treatment modalities and the possible strategies, which could be applied for the therapy of this occurrence. Results: Since CNV can often originate from posterior pole lesions and can be hard to identify, an accurate examination is mandatory in order to identify the correct diagnosis. In the majority of cases, fluorescein angiography (FA), indocyanine green angiography (ICGA) and optical coherence tomography (OCT) enable the determination of the clinical characteristics of the CNV. An infectious disease should be looked for to include a suitable therapy when available. The treatment strategy for CNV secondary to noninfectious uveal inflammations should be directed at controlling the inflammatory process. Systemic corticosteroids with or without immunosuppressive agents are indicated even when the CNV occurs with apparently inactive uveitis: Chronic subclinical inflammation can be the basis for the pathogenesis of CNV. Additional therapies aimed directly at the neovascular process, such as the intravitreal anti-Vascular Endothelial Growth Factor (VEGF) agents, are recommended particularly when the therapy shows an insufficient response. Conclusion: CNV secondary to uveitis is a severe sequela leading to significant visual impairment. ICGA is mandatory in order to obtain relevant information about the choroidal status. Several therapeutic options have been considered, but no guidelines are provided at the moment. Moreover, the current data are still only based on case reports or small series. For such reasons, further trials are mandatory to validate the preliminary available results. PMID:20404991

  7. Isozyme variation among teak (Tectona grandis L.f.) provenances.

    PubMed

    Kertadikara, A W; Prat, D

    1995-05-01

    Fourteen enzyme systems were analysed in leaf parenchyma of nine native and introduced populations of teak. These enzyme systems were encoded by 20 putative loci of which 18 were polymorphic. Populations showed a general lack of heterozygosity (average FIS = 0.11). On average over the 18 polymorphic loci, the genetic differentiation among provenances varied according to the estimator: 0.09 for GST, 0.12 for FST and 0.19 for δ. The cluster analysis showed two main gene pools, the first consisted of the Indian provenances and the second of African, Indonesian and Thai provenances. Genetic distances among populations of the same group were similar, and lower than the genetic distances between populations from different groups. The factorial analysis on genotypes of seedlings also showed the same geographic differentiation into two major groups. The possible natural distribution of teak in Java is discussed. PMID:24172922

  8. Using Domain Requirements to Achieve Science-Oriented Provenance

    SciTech Connect

    Stephan, Eric G; Halter, Todd D; Critchlow, Terence J; Pinheiro Da Silva, Paulo; Salayandia, Leonardo

    2010-06-18

    Using Domain Requirements to Achieve Science-Oriented Provenance Eric Stephan1 Todd Halter1 Terence Critchlow1 Paulo Pinheiro da Silva2 Leonardo Salayandia2 1 Pacific Northwest National Laboratory, Richland WA, USA 2 University of Texas at El Paso, El Paso TX, USA Abstract. The US Department of Energy (DOE) Atmospheric Radi- ation Measurement Program (ARM) is adopting the use of formalized provenance to support observational data products produced by ARM operations and relied upon by researchers. Because of the diversity of needs in the climate community provenance will need to be conveyed in a domain-oriented context. This paper explores a use case where semantic abstract workflows (SAW) are employed as a means to filter, aggregate, and contextually describe the historical events responsible for the ARM data product the scientist is relying upon.

  9. Environment and the inflammatory bowel diseases.

    PubMed

    Frolkis, Alexandra; Dieleman, Levinus A; Barkema, Herman W; Panaccione, Remo; Ghosh, Subrata; Fedorak, Richard N; Madsen, Karen; Kaplan, Gilaad G

    2013-03-01

    Inflammatory bowel diseases (IBD), which consists of Crohn disease and ulcerative colitis, are chronic inflammatory conditions of the gastrointestinal tract. In genetically susceptible individuals, the interaction between environmental factors and normal intestinal commensal flora is believed to lead to an inappropriate immune response that results in chronic inflammation. The incidence of IBD have increased in the past century in developed and developing countries. The purpose of the present review is to summarize the current knowledge of the association between environmental risk factors and IBD. A number of environmental risk factors were investigated including smoking, hygiene, microorganisms, oral contraceptives, antibiotics, diet, breastfeeding, geographical factors, pollution and stress. Inconsistent findings among the studies highlight the complex pathogenesis of IBD. Additional studies are necessary to identify and elucidate the role of environmental factors in IBD etiology. PMID:23516681

  10. Bone Loss Triggered by the Cytokine Network in Inflammatory Autoimmune Diseases

    PubMed Central

    Amarasekara, Dulshara Sachini; Yu, Jiyeon; Rho, Jaerang

    2015-01-01

    Bone remodeling is a lifelong process in vertebrates that relies on the correct balance between bone resorption by osteoclasts and bone formation by osteoblasts. Bone loss and fracture risk are implicated in inflammatory autoimmune diseases such as rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, and systemic lupus erythematosus. The network of inflammatory cytokines produced during chronic inflammation induces an uncoupling of bone formation and resorption, resulting in significant bone loss in patients with inflammatory autoimmune diseases. Here, we review and discuss the involvement of the inflammatory cytokine network in the pathophysiological aspects and the therapeutic advances in inflammatory autoimmune diseases. PMID:26065006

  11. Chronic Pruritus: Clinics and Treatment

    PubMed Central

    Grundmann, Sonja

    2011-01-01

    Chronic pruritus, one of the main symptoms in dermatology, is often intractable and has a high impact on patient's quality of life. Beyond dermatologic disorders, chronic pruritus is associated with systemic, neurologic as well as psychologic diseases. The pathogenesis of acute and chronic (>6 weeks duration) pruritus is complex and involves in the skin a network of resident (e.g., sensory neurons) and transient inflammatory cells (e.g., lymphocytes). In the skin, several classes of histamine-sensitive or histamine-insensitve C-fibers are involved in itch transmission. Specific receptors have been discovered on cutaneous and spinal neurons to be exclusively involved in the processing of pruritic signals. Chronic pruritus is notoriously difficult to treat. Newer insights into the underlying pathogenesis of pruritus have enabled novel treatment approaches that target the pruritus-specific pathophysiological mechanism. For example, neurokinin-1 antagonists have been found to relieve chronic pruritus. PMID:21738356

  12. Provenance in Data Interoperability for Multi-Sensor Intercomparison

    NASA Technical Reports Server (NTRS)

    Lynnes, Chris; Leptoukh, Greg; Berrick, Steve; Shen, Suhung; Prados, Ana; Fox, Peter; Yang, Wenli; Min, Min; Holloway, Dan; Enloe, Yonsook

    2008-01-01

    As our inventory of Earth science data sets grows, the ability to compare, merge and fuse multiple datasets grows in importance. This requires a deeper data interoperability than we have now. Efforts such as Open Geospatial Consortium and OPeNDAP (Open-source Project for a Network Data Access Protocol) have broken down format barriers to interoperability; the next challenge is the semantic aspects of the data. Consider the issues when satellite data are merged, cross-calibrated, validated, inter-compared and fused. We must match up data sets that are related, yet different in significant ways: the phenomenon being measured, measurement technique, location in space-time or quality of the measurements. If subtle distinctions between similar measurements are not clear to the user, results can be meaningless or lead to an incorrect interpretation of the data. Most of these distinctions trace to how the data came to be: sensors, processing and quality assessment. For example, monthly averages of satellite-based aerosol measurements often show significant discrepancies, which might be due to differences in spatio- temporal aggregation, sampling issues, sensor biases, algorithm differences or calibration issues. Provenance information must be captured in a semantic framework that allows data inter-use tools to incorporate it and aid in the intervention of comparison or merged products. Semantic web technology allows us to encode our knowledge of measurement characteristics, phenomena measured, space-time representation, and data quality attributes in a well-structured, machine-readable ontology and rulesets. An analysis tool can use this knowledge to show users the provenance-related distrintions between two variables, advising on options for further data processing and analysis. An additional problem for workflows distributed across heterogeneous systems is retrieval and transport of provenance. Provenance may be either embedded within the data payload, or transmitted

  13. Chronic urticaria: recent advances.

    PubMed

    Greaves, Malcolm W; Tan, Kian Teo

    2007-10-01

    Chronic urticaria is an umbrella term, which encompasses physical urticarias, chronic "idiopathic" urticaria and urticarial vasculitis. It is important to recognize patients with physical urticarias as the investigation and treatment differs in important ways from patients with idiopathic chronic urticaria or urticarial vasculitis. Although relatively uncommon, urticarial vasculitis is an important diagnosis to make and requires histological confirmation by biopsy. Underlying systemic disease and systemic involvement, especially of the kidneys, should be sought. It is now recognized that chronic "idiopathic" urticaria includes a subset with an autoimmune basis caused by circulating autoantibodies against the high affinity IgE receptor (FceR1) and less commonly against IgE. Although the autologous serum skin test has been proven useful in prompting search for and characterization of circulating wheal-producing factors in chronic urticaria, its specificity as a screening test for presence of functional anti-FceR1 is low, and confirmation by demonstration of histamine-releasing activity in the patient's serum must be the benchmark test in establishing this diagnosis. Improved screening tests are being sought; for example, ability of the chronic urticaria patient's serum to evoke expression of CD 203c on donor human basophils is showing some promise. The strong association between autoimmune thyroid disease and autoimmune urticaria is also an area of ongoing research. Drug treatment continues to be centered on the H1 antihistamines, and the newer second-generation compounds appear to be safe and effective even in off-label dosage. Use of systemic steroids should be confined to special circumstances such as tapering regimens for acute flare-ups. Use of leukotriene antagonists is becoming popular, but the evidence for efficacy is conflicting. Cyclosporin is also effective and can be used in selected cases of autoimmune urticaria, and it is also effective in non

  14. An extensible framework for provenance in human terrain visual analytics.

    PubMed

    Walker, Rick; Slingsby, Aiden; Dykes, Jason; Xu, Kai; Wood, Jo; Nguyen, Phong H; Stephens, Derek; Wong, B L William; Zheng, Yongjun

    2013-12-01

    We describe and demonstrate an extensible framework that supports data exploration and provenance in the context of Human Terrain Analysis (HTA). Working closely with defence analysts we extract requirements and a list of features that characterise data analysed at the end of the HTA chain. From these, we select an appropriate non-classified data source with analogous features, and model it as a set of facets. We develop ProveML, an XML-based extension of the Open Provenance Model, using these facets and augment it with the structures necessary to record the provenance of data, analytical process and interpretations. Through an iterative process, we develop and refine a prototype system for Human Terrain Visual Analytics (HTVA), and demonstrate means of storing, browsing and recalling analytical provenance and process through analytic bookmarks in ProveML. We show how these bookmarks can be combined to form narratives that link back to the live data. Throughout the process, we demonstrate that through structured workshops, rapid prototyping and structured communication with intelligence analysts we are able to establish requirements, and design schema, techniques and tools that meet the requirements of the intelligence community. We use the needs and reactions of defence analysts in defining and steering the methods to validate the framework. PMID:24051780

  15. From Observation to Impacts: Provenance for Earth Science Resources

    NASA Astrophysics Data System (ADS)

    Hua, H.; Tilmes, C.; Fox, P. A.; Zednik, S.; Duggan, B.; Aulenbach, S.; Wilson, B. D.; Manipon, G. J. M.; Privette, A. P.

    2014-12-01

    NASA's Earth Science Data Systems Working Group (ESDSWG) on Provenance is working on a provenance specification for use in Earth science data systems to capture, consume, and interpret the end-to-end data life cycle information. Based on W3C PROV, this Earth Science extension can be used as an interoperable specification for representing Earth science resources that includes observations by instruments, data producers, data processing systems, data archive centers, data users, analysis findings, and societal impacts. NASA is participating in the Big Earth Data Initiative (BEDI) and also leading a related Climate Data Initiative (CDI) effort. Under CDI, NASA is also working with the U.S. Global Change Research Program (USGCRP) and the U.S. Group on Earth Observations (USGEO) to identify and make interoperable relevant data from multiple interagency sources. These interagency efforts will improve the discoverability, accessibility, and usability of Federal data and information products derived from civil Earth observations. We will present our progress to develop a provenance specification for representing Earth science resources from observation to impacts and how it can be used to support these initiatives. We will show how it can be used in earth science data systems to automatically capture, consume, and interpret provenance information using semantic technologies.

  16. Gabapentin for Chronic Refractory Cancer Cough.

    PubMed

    Atreya, Shrikant; Kumar, Gaurav; Datta, Soumitra Shankar

    2016-01-01

    Vagal sensory neuropathy or vagal hypersensitivity has been implicated in the pathophysiology of chronic cough. Earlier reports have shown gabapentin to be effective in sensory laryngeal neuropathy and symptom conditions that have a proven neural origin. We present a case report of a patient with chronic refractory cough due to a soft tissue mass in the lung that caused compression of the mediastinal structures. The patient was successfully treated with gabapentin with reduction in the cough intensity, duration, and frequency. PMID:26962287

  17. Gabapentin for Chronic Refractory Cancer Cough

    PubMed Central

    Atreya, Shrikant; Kumar, Gaurav; Datta, Soumitra Shankar

    2016-01-01

    Vagal sensory neuropathy or vagal hypersensitivity has been implicated in the pathophysiology of chronic cough. Earlier reports have shown gabapentin to be effective in sensory laryngeal neuropathy and symptom conditions that have a proven neural origin. We present a case report of a patient with chronic refractory cough due to a soft tissue mass in the lung that caused compression of the mediastinal structures. The patient was successfully treated with gabapentin with reduction in the cough intensity, duration, and frequency. PMID:26962287

  18. [Anti-inflammatory effects of tea-flavonoids].

    PubMed

    Hoensch, H; Oertel, R

    2012-12-01

    Tea flavonoids belong to the large group of polyphenols and display antioxidative, anti-inflammatory and anti-neoplastic activities. These phytochemicals are xenobiotics and are synthesized by tea plants such as Camellia sinensis and Camomilla recucita. These botanicals exhibit in vivo activities similar to that of biologicals which are widely used for chronic inflammatory diseases (rheumatoid arthritis, chronic inflammatory bowel disease). Epigallocathechin gallate and apigenin from these plants inhibit cytokines, chemokines and activated immune cells in vivo and in vitro. Clinical disorders with induced inflammatory pathways could benefit from flavonoid treatment. Dietary supplementation with specific tea-flavonoids could be used for Crohn's disease, ulcerative colitis and irritable bowel syndrome. Suppression of cytokine production could ultimately lead to inhibition of carcinogenesis. This mechanism could explain why flavonoids are effective in the prevention of intestinal neoplasia. This innovative new form of therapy should be tested in controlled, randomized clinical studies. PMID:23233307

  19. Chronic cholecystitis

    MedlinePlus

    Cholecystitis - chronic ... Most of the time, chronic cholecystitis is caused by repeated attacks of acute (sudden) cholecystitis. Most of these attacks are caused by gallstones in the gallbladder. These ...

  20. Chronic Bronchitis

    MedlinePlus

    Bronchitis is an inflammation of the bronchial tubes, the airways that carry air to your lungs. It ... chest tightness. There are two main types of bronchitis: acute and chronic. Chronic bronchitis is one type ...

  1. Geospatial Data Provenance in the Semantic Web Environment

    NASA Astrophysics Data System (ADS)

    di, L.; Yue, P.

    2008-12-01

    Geospatial data will grow to multi-exabytes very soon. The major form of geospatial data is imagery collected by the Earth observing community through remote sensing methods. Those data, along with their derived products and model outputs, are archived in many data centers around the world. Geospatial data has to be converted to user-specific information and knowledge before they become useful. Such a user-specific information and knowledge is normally derived from multi-source data through a set of geoprocess steps. Recent technology advances in the united representation of geospatial data, information, and knowledge, the geospatial semantic web, the geospatial interoperability, and the artificial intelligence have made the automatic derivation of user-specific information and knowledge from diverse data sources in the web service environment possible. A prototype system for proofing such technologies has been constructed and successfully demonstrated. An operational systems is being development. With the ontology support, the system automatically constructs the executable workflow based on users' descriptions of what they want and the available services and the input data over the web, and execute the workflow to generate the user- specific product. In order for users to have the confidence to use such automatically generated products in real applications, complete and accurate provenance information must be provided to users, even before such user-specific products are generated. In this presentation, we will discuss the representation of geospatial data provenance, the automatic capturing of geospatial data provenance in the semantic web environment, and the management of geospatial data provenance. We will also discuss a prototype provenance management system that allows the users to query and access providence information.

  2. Representing annotation compositionality and provenance for the Semantic Web

    PubMed Central

    2013-01-01

    Background Though the annotation of digital artifacts with metadata has a long history, the bulk of that work focuses on the association of single terms or concepts to single targets. As annotation efforts expand to capture more complex information, annotations will need to be able to refer to knowledge structures formally defined in terms of more atomic knowledge structures. Existing provenance efforts in the Semantic Web domain primarily focus on tracking provenance at the level of whole triples and do not provide enough detail to track how individual triple elements of annotations were derived from triple elements of other annotations. Results We present a task- and domain-independent ontological model for capturing annotations and their linkage to their denoted knowledge representations, which can be singular concepts or more complex sets of assertions. We have implemented this model as an extension of the Information Artifact Ontology in OWL and made it freely available, and we show how it can be integrated with several prominent annotation and provenance models. We present several application areas for the model, ranging from linguistic annotation of text to the annotation of disease-associations in genome sequences. Conclusions With this model, progressively more complex annotations can be composed from other annotations, and the provenance of compositional annotations can be represented at the annotation level or at the level of individual elements of the RDF triples composing the annotations. This in turn allows for progressively richer annotations to be constructed from previous annotation efforts, the precise provenance recording of which facilitates evidence-based inference and error tracking. PMID:24268021

  3. THE EFFECTS OF COMBINATORIAL EXPOSURE OF PRO-INFLAMMATORY AND ANTI-INFLAMMATORY CYTOKINES ON AIRWAY EPITHELIAL CELL RELEASE OF CHEMOTACTIC MEDIATORS

    EPA Science Inventory

    Asthma is a chronic inflammatory disorder of the airways affecting nearly 15 million individuals nationally. Within the inflamed asthmatic airway there exist complex interactions between many cells and the cytokines they release, in particular mast cells, eosinophils, T-lymphocy...

  4. Molecular Mechanisms of Chronic Kidney Transplant Rejection via Large-Scale Proteogenomic Analysis of Tissue Biopsies

    PubMed Central

    Nakorchevsky, Aleksey; Hewel, Johannes A.; Kurian, Sunil M.; Mondala, Tony S.; Campbell, Daniel; Head, Steve R.; Marsh, Christopher L.; Yates, John R.

    2010-01-01

    The most common cause of kidney transplant failure is the poorly characterized histopathologic entity interstitial fibrosis and tubular atrophy (IFTA). There are no known unifying mechanisms, no effective therapy, and no proven preventive strategies. Possible mechanisms include chronic immune rejection, inflammation, drug toxicity, and chronic kidney injury from secondary factors. To gain further mechanistic insight, we conducted a large-scale proteogenomic study of kidney transplant biopsies with IFTA of varying severity. We acquired proteomic data using tandem mass spectrometry with subsequent quantification, analysis of differential protein expression, validation, and functional annotations to known molecular networks. We performed genome-wide expression profiling in parallel. More than 1400 proteins with unique expression profiles traced the progression from normal transplant biopsies to biopsies with mild to moderate and severe disease. Multiple sets of proteins were mapped to different functional pathways, many increasing with histologic severity, including immune responses, inflammatory cell activation, and apoptosis consistent with the chronic rejection hypothesis. Two examples include the extensive population of the alternative rather than the classical complement pathway, previously not appreciated for IFTA, and a comprehensive control network for the actin cytoskeleton and cell signaling of the acute-phase response. In summary, this proteomic effort using kidney tissue contributes mechanistic insight into several biologic processes associated with IFTA. PMID:20093355

  5. Inflammatory Bowel Disease in Australasian Children and Adolescents

    PubMed Central

    Day, A. S.; Lemberg, D. A.; Gearry, R. B.

    2014-01-01

    Many reports indicate increasing rates of inflammatory bowel disease, with data also showing changing patterns of this chronic disease in children and adolescents. This review focuses upon the available data of the epidemiology of inflammatory bowel disease in children and adolescents in Australia and New Zealand (collectively termed Australasia). Recent data show high incidence of IBD (especially Crohn disease) in this area and indicate rising rates of IBD in children and adolescents. PMID:24799892

  6. Inflammatory bowel disease in australasian children and adolescents.

    PubMed

    Day, A S; Lemberg, D A; Gearry, R B

    2014-01-01

    Many reports indicate increasing rates of inflammatory bowel disease, with data also showing changing patterns of this chronic disease in children and adolescents. This review focuses upon the available data of the epidemiology of inflammatory bowel disease in children and adolescents in Australia and New Zealand (collectively termed Australasia). Recent data show high incidence of IBD (especially Crohn disease) in this area and indicate rising rates of IBD in children and adolescents. PMID:24799892

  7. Nutritional aspect of pediatric inflammatory bowel disease: its clinical importance

    PubMed Central

    Kim, Seung

    2015-01-01

    Inflammatory bowel disease (IBD) is a chronic inflammatory disease mainly affecting the gastrointestinal tract. The incidence of the disease is rapidly increasing worldwide, and a number of patients are diagnosed during their childhood or adolescence. Aside from controlling the gastrointestinal symptoms, nutritional aspects such as growth, bone mineral density, anemia, micronutrient deficiency, hair loss, and diet should also be closely monitored and managed by the pediatric IBD team especially since the patients are in the development phase. PMID:26576179

  8. Chronic Bronchitis

    MedlinePlus

    ... carry air to your lungs. It causes a cough that often brings up mucus. It can also cause shortness of breath, wheezing, a low fever, and chest tightness. There are two main types of bronchitis: acute and chronic. Chronic bronchitis is one type of COPD (chronic ...

  9. Seamless Provenance Representation and Use in Collaborative Science Scenarios

    NASA Astrophysics Data System (ADS)

    Missier, P.; Ludaescher, B.; Bowers, S.; Altintas, I.; Anand, M. K.; Dey, S.; Sarkar, A.; Shrestha, B.; Goble, C.

    2010-12-01

    The notion of sharing scientific data has only recently begun to gain ground in science, where data is still considered a private asset. There is growing evidence, however, that the benefits of scientific collaboration through early data sharing during the course of a science project may outgrow the risk of losing exclusive ownership of the data. As exemplar success stories are making the headlines[1], principles of effective information sharing have become the subject of e-science research. In particular, any piece of published data should be self-describing, to the extent necessary for consumers to determine its suitability for reuse in their own projects. This is accomplished by associating a body of formally specified and machine-processable metadata to the data. When data is produced and reused by independent groups, however, metadata interoperability issues emerge. This is the case for provenance, a form of metadata that describes the history of a data product, Y. Provenance is typically expressed as a graph-structured set of dependencies that account for the sequence of computational or interactive steps that led to Y, often starting from some primary, observational data. Traversing dependency graphs is one of the mechanisms used to answer questions on data reliability. In the context of the NSF DataONE project[2], we have been studying issues of provenance interoperability in scientific collaboration scenarios. Consider a first scientist, Alice, who publishes a data product X along with its provenance, and a second scientist who further transforms X into a new product Y, also along with its provenance. A third scientist, who is interested in Y, expects to be able to trace Y's history up to the inputs used by Alice. This is only possible, however, if provenance accumulates into a single, uniform graph that can be seamlessly traversed. This becomes problematic when provenance is captured using different tools and computational models (i.e. workflow systems