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Sample records for chronic inflammatory demyelinating

  1. Chronic inflammatory demyelinative polyneuropathy

    DEFF Research Database (Denmark)

    Said, Gérard; Krarup, Christian

    2013-01-01

    Chronic inflammatory demyelinative polyneuropathy (CIDP) is an acquired polyneuropathy presumably of immunological origin. It is characterized by a progressive or a relapsing course with predominant motor deficit. The diagnosis rests on the association of non-length-dependent predominantly motor...

  2. Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

    Science.gov (United States)

    ... and abnormal sensations. CIDP is closely related to Guillain-Barre syndrome and it is considered the chronic counterpart ... and abnormal sensations. CIDP is closely related to Guillain-Barre syndrome and it is considered the chronic counterpart ...

  3. Intravenous immunoglobulin treatment in chronic inflammatory demyelinating polyneuropathy

    NARCIS (Netherlands)

    P.A. van Doorn (Pieter)

    1990-01-01

    textabstractPatients with a chronic inflammatory demyelinating polyneuropathy (CIDP) may respond to treatment with corticosteroids and to plasmapheresis, which was demonstrated in controlled clinical studies. In an uncontrolled study it was found that 13/17 CIDP patients had a rapid and

  4. Epidemiology of chronic inflammatory demyelinating polyneuropathy abroad and in Russia

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    T. E. Popova

    2015-01-01

    Full Text Available Current article provides an overview of the results of epidemiological studies of chronic inflammatory demyelinating polyneuropathy (CIDP in Russia and abroad. It is shown that the prevalence of CIDP is different in countries, due to the use of different diagnostic criteria. It should be noted that the reliability of epidemiological prevalence and incidence is affected by difficulties of diagnosis of atypical forms of the disease.

  5. Subcutaneous immunoglobulin preserves muscle strength in chronic inflammatory demyelinating polyneuropathy

    DEFF Research Database (Denmark)

    Markvardsen, Lars Høj; Harbo, Thomas; Sindrup, Søren Hein

    2014-01-01

    evaluated after 3, 6 and 12 months. Primary end-points were changes in muscle strength evaluated by isokinetic dynamometry in four affected muscle groups and a composite score of muscle performance and function tests, including Medical Research Council (MRC) score, grip strength, 40-m walking test (40-MWT......BACKGROUND AND PURPOSE: Subcutaneous immunoglobulin (SCIG) is superior to placebo treatment for maintenance of muscle strength during 12 weeks in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). The present study evaluated whether SCIG preserves muscle strength for 1 year......) and nine-hole peg test (9-HPT). Secondary end-points were changes of each of the listed parameters at each time point as well as an overall disability sum score (ODSS). RESULTS: The dose of SCIG was significantly unaltered during the follow-up period. Overall the isokinetic dynamometry value increased by 7...

  6. Chronic inflammatory demyelinating polyneuropathy associated with diabetes mellitus

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    Farzad Fatehi

    2013-01-01

    Full Text Available 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.

  7. Thrombocytosis distinguishes POEMS syndrome from chronic inflammatory demyelinating polyneuropathy.

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    Naddaf, Elie; Dispenzieri, Angela; Mandrekar, Jay; Mauermann, Michelle L

    2015-10-01

    POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, and skin changes) syndrome may be mistaken for chronic inflammatory demyelinating polyneuropathy (CIDP). Differentiating the 2 entities is crucial, as there are major treatment implications. We compared platelet counts in 136 POEMS patients and 67 CIDP controls. Of the patients with POEMS, 53.7% had thrombocytosis, compared with 1.5% of those with CIDP (P < 0.0001). The median platelet count in patients with POEMS was 467,000/μl compared with 275,000/μl in those with CIDP (P < 0.0001). Thrombocytosis is a helpful indicator to prompt clinicians to consider the diagnosis of POEMS syndrome in patients who are thought to have CIDP, and is an important reminder of the increased risk of thrombotic events in POEMS syndrome. © 2015 Wiley Periodicals, Inc.

  8. Intravenous immunoglobulin response in treatment-naïve chronic inflammatory demyelinating polyradiculoneuropathy

    NARCIS (Netherlands)

    Kuitwaard, Krista; Hahn, Angelika F.; Vermeulen, Marinus; Venance, Shannon L.; van Doorn, Pieter A.

    2015-01-01

    There is no consensus on which treatment should be used preferentially in individual patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Patients unlikely to respond to intravenous immunoglobulin (IVIg) could be prescribed corticosteroids first to avoid high cost and a delayed

  9. Pyrexia-associated Relapse in Chronic Inflammatory Demyelinating Polyradiculoneuropathy: A Case Report.

    Science.gov (United States)

    Ueda, Jun; Yoshimura, Hajime; Kohara, Nobuo

    2018-04-27

    Chronic inflammatory demyelinating polyradiculoneuropathy is a relapsing-remitting or chronic progressive demyelinating polyradiculoneuropathy. We report the case of a patient with chronic inflammatory demyelinating polyradiculoneuropathy who experienced relapses on four occasions after experiencing pyrexia and flu-like symptoms. Our patient showed characteristic features, such as relapse after pyrexia and flu-like symptoms, remission after pyretolysis without treatment, and the absence of remarkable improvement in a nerve conduction study in the remission phase. The serum level of tumor necrosis factor-α was elevated in the relapse phase and reduced in the remission phase; thus, the induction of cytokine release by viral infection might have caused the relapses.

  10. Diagnostic criteria of chronic inflammatory demyelinating polyneuropathy in diabetes mellitus.

    Science.gov (United States)

    Lotan, I; Hellman, M A; Steiner, I

    2015-10-01

    The possibility of co-association between diabetes mellitus (DM) and chronic inflammatory demyelinating polyneuropathy (CIDP) has long been a focus of interest as well as of clinical significance. As CIDP is a potentially treatable condition, it is diagnosis in the context of DM is of great importance. However, diagnostic criteria to identify CIDP in patients with diabetes are not available. We propose a diagnostic tool that should help clinicians to decide what is the probability that a patient with diabetes might have CIDP. We list several clinical, electrophysiological, and laboratory parameters that, when combined, have the power of discriminating an immune-mediated neuropathy in patients with DM. By summing the points assigned to each of these parameters, we define four levels of probability for a patient with diabetes to have CIDP. To analyze the validity of the diagnostic toll, we applied it in three different patient populations: (i) Patients with diabetes with peripheral neuropathy, (ii) Patients with CIDP without DM, and (iii) Patients with diabetes with CIDP. The scores of patients with diabetes without CIDP ranged from -7 to 2, while those of patients with DM-CIDP ranged from 2 to 20. The scores of non-diabetic patients with CIDP were similar to those of patients with DM-CIDP and ranged from 6 to 16. The mean score of patients with DM-CIDP was 9.083, while the score of patients with CIDP was 11.16 and that of patients with diabetic polyneuropathy was -3.59. These results show that this diagnostic tool is able to identify patients with diabetes with overlapping CIDP. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

    NARCIS (Netherlands)

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

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Mohamed Mahdi-Rogers

    2010-03-01

    Full Text Available Mohamed Mahdi-Rogers, Yusuf A RajaballyNeuromuscular Clinic, Department of Neurology, University Hospitals of Leicester, Leicester, UKAbstract: 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.Keywords: chronic inflammatory demyelinating polyneuropathy, intravenous immunoglobulin, pathogenesis, treatment

  13. Subcutaneous immunoglobulin in responders to intravenous therapy with chronic inflammatory demyelinating polyradiculoneuropathy

    DEFF Research Database (Denmark)

    Markvardsen, Lars Høj; Debost, J-C; Harbo, Thomas

    2013-01-01

    BACKGROUND AND PURPOSE: We hypothesized that subcutaneous administration of immunoglobulins (SCIG) in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is feasible, safe and superior to treatment with saline for the performance of muscle strength. METHODS: Thirty patients with motor...... Research Council (MRC) score, grip strength, standardized electrophysiological recordings from three nerves, and plasma IgG levels were evaluated. RESULTS: SCIG treatment was well tolerated in all 14 patients. Six patients complained of mild side-effects at the injection site. In the SCIG group...

  14. Cerebrospinal Fluid Cytokine Expression Profile in Multiple Sclerosis and Chronic Inflammatory Demyelinating Polyneuropathy.

    Science.gov (United States)

    Bonin, Serena; Zanotta, Nunzia; Sartori, Arianna; Bratina, Alessio; Manganotti, Paolo; Trevisan, Giusto; Comar, Manola

    2018-02-01

    Cerebrospinal fluid (CSF) analysis in patients with particular neurologic disorders is a powerful tool to evaluate specific central nervous system inflammatory markers for diagnostic needs, because CSF represents the specific immune micro-environment to the central nervous system. CSF samples from 49 patients with multiple sclerosis (MS), chronic inflammatory demyelinating polyneuropathy (CIDP), and non-inflammatory neurologic disorders (NIND) as controls were submitted to protein expression profiles of 47 inflammatory biomarkers by multiplex Luminex bead assay to investigate possible differences in the inflammatory process for MS and CIDP. Our results showed differences in CSF cytokine levels in MS and CIDP; in particular, IL12 (p40) was significantly highly expressed in MS in comparison with CIDP and NIND, while SDF-1α and SCGF-β were significantly highly expressed in CIDP cohort when compared to MS and NIND. IL-9, IL-13, and IL-17 had higher expression levels in NIND if compared with the other groups. Our study showed that, despite some common pathogenic mechanisms, central and peripheral nervous system demyelinating diseases, such as MS and CIDP, differ in some specific inflammatory soluble proteins in CSF, underlining differences in the immune response involved in those autoimmune diseases.

  15. Unusual features in chronic inflammatory demyelinating polyneuropathy: Good outcome after prolonged ventilatory support

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    Sanjeev Jha

    2011-01-01

    Full Text Available Severe respiratory muscle paralysis and ventilatory failure is rare in chronic inflammatory demyelinating polyneuropathy (CIDP. We report a 14 year child who presented with respiratory failure, bulbar and multiple cranial nerves involvement along with bilateral phrenic nerve paralysis. He was diagnosed with CIDP after electrophysiological evaluation. He required AMBU ventilation for about 4 months (including domiciliary use, after which he recovered significantly. Along with several unusual features of CIDP, this report highlights good example of steady basic intensive care to save lives and rewarding outcome of prolonged respiratory support, provided by AMBU ventilation which is a rather primitive, but inexpensive device.

  16. Changes in spatiotemporal gait parameters following intravenous immunoglobulin treatment for chronic inflammatory demyelinating polyneuropathy.

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    Vo, Mary L; Chin, Russell L; Miranda, Caroline; Latov, Norman

    2017-10-01

    Gait impairment is a common presenting symptom in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). However, gait parameters have not previously been evaluated in detail as potential independent outcome measures. We prospectively measured changes in spatiotemporal gait parameters of 20 patients with CIDP at baseline and following treatment with intravenous immunoglobulin (IVIG), using GAITRite® a computerized walkway system with embedded sensors. Overall, study patients showed significant improvements in gait velocity, cadence, stride length, double support time, stance phase, and swing phase following IVIG treatment. Mean changes in velocity, stance phase, and swing phase, exhibited the greatest statistical significance among the subgroup that exhibited clinically meaningful improvement in Inflammatory Neuropathy Cause and Treatment disability score, Medical Research Council sum score, and grip strength. Assessment of gait parameters, in particular velocity, step phase and swing phase, is a potentially sensitive outcome measure for evaluating treatment response in CIDP. Muscle Nerve 56: 732-736, 2017. © 2017 Wiley Periodicals, Inc.

  17. Chronic Inflammatory Demyelinating Polyneuropathy in Children: A Review of Clinical Characteristics and Recommendations for Treatment

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    Narges Karimi

    2015-07-01

    Full Text Available Context: Chronic inflammatory demyelinating polyradiculopathy (CIDP is an acquired and autoimmune neuropathy, characterized by a chronic, rapidly progressive, symmetric weakness. In children, abnormal gait is as a first symptom of muscle weakness. Evidence Acquisition: The diagnosis of CIDP is on the basis of clinical characteristics, electrodiagnostic that shows the severity of the disease, lumbar puncture and spine magnetic resonance imaging (MRI. Results: The first-line treatments in childhood CIDP are intravenous immunoglobulin (IVIG, corticosteroids, and plasmapheresis. Response to first-line therapies is usually satisfactory; nevertheless, recommendations regarding the choice of second-line therapy can only be prepared on the basis of the existing practice described in some of the case reports. Conclusions: This review demonstrated the clinical presentation, diagnosis, and treatment of childhood CIDP.

  18. Nerve sonography in multifocal motor neuropathy and chronic inflammatory demyelinating polyneuropathy

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    D. S. Druzhinin

    2016-01-01

    Full Text Available The quantitative ultrasound characteristics (USC of the median, ulnar nerve at different levels and the spinal nerves in patients with multifocal motor neuropathy (MMN; n=13; 40,4 ± 12,6 years old and chronic inflammatory demyelinating polyneuropathy (CIDP; n = 7; 47,3 ± 11,2 year old did not reveal statistical difference in cross sectional area (CSA between analyzed groups. Patients with MMN have more pronounced asymmetry of CSA in comparison with CIDP patients which have a symmetrical pattern of diffuse nerve involvement. Quantitative USC has shown to be not informative enough in differentiation of MMN and CIDP. The qualitative analysis (QA according to 3 described types of nerve changes has shown that CIDP is characterized by the prevalence of type 3 pattern (85.8 % while MMN – by type 2 (69.2 %. The sensitivity and specificity of proposed QA patterns in nerve USC need to be analyzed in additional investigations. 

  19. Treatment of pediatric chronic inflammatory demyelinating polyneuropathy: Challenges, controversies, and questions

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    Jay Desai

    2015-01-01

    Full Text Available Pediatric chronic inflammatory demyelinating polyneuropathy (CIDP is an uncommon acquired disorder of unknown cause, presumed to have an immunological basis. We report 20 patients seen at Children′s Hospital Los Angeles over a period of 10 years. The outcome of our patients was favorable in a vast majority with good response to various treatments instituted. However, residual neurologic deficit was common. The choice of treatment modality was empirical and selected by the treating neurologist. Intravenous immunoglobulin (IVIG and corticosteroids were most commonly utilized for treatment. Plasmapheresis, mycophenolate mofetil, rituximab, cyclophosphamide, azathioprine, and abatacept were added if the patients were refractory to IVIG or became corticosteroid dependent. The spectrum of disease severity ranged from a single monophasic episode, to multiphasic with infrequent relapses with good response to IVIG, to progressive disease refractory to multiple therapies.

  20. A recurrence of Guillain-Barr and eacute; syndrome or a case of acute-onset chronic inflammatory demyelinating polyneuropathy in the course of chronic hepatitis B?

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    Guner Celik Koyuncu

    2016-12-01

    Full Text Available Chronic inflammatory demyelinating polyneuropathy is a demyelinating polyneuropathy characterized by distal/proximal weakness, which shows gradual progression over a period of 8 weeks or longer. Guillan-Barre Syndrome is a condition characterized by acute monophasic paralysis typically following an infectious assault, and it usually peaks in severity over 3-4 weeks at most. Although rare, there are acute-onset chronic inflammatory demyelinating polyneuropathy cases that show progression over a period shorter than 4 weeks, as is the case in Guillan-Barre Syndrome .This report discusses a case of chronic inflammatory demyelinating polyneuropathy in a HBsAg-positive patient, which started as Guillan-Barre Syndrome but showed 3 recurrences within 6 months, each with rapidly progressing quadriplegia, respiratory arrest, and elevated liver enzymes and HBV DNA. [Cukurova Med J 2016; 41(4.000: 782-786

  1. Nerve Ultrasound Predicts Treatment Response in Chronic Inflammatory Demyelinating Polyradiculoneuropathy-a Prospective Follow-Up.

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    Härtig, Florian; Ross, Marlene; Dammeier, Nele Maria; Fedtke, Nadin; Heiling, Bianka; Axer, Hubertus; Décard, Bernhard F; Auffenberg, Eva; Koch, Marilin; Rattay, Tim W; Krumbholz, Markus; Bornemann, Antje; Lerche, Holger; Winter, Natalie; Grimm, Alexander

    2018-04-01

    As reliable biomarkers of disease activity are lacking, monitoring of therapeutic response in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) remains a challenge. We sought to determine whether nerve ultrasound and electrophysiology scoring could close this gap. In CIDP patients (fulfilling EFNS/PNS criteria), we performed high-resolution nerve ultrasound to determine ultrasound pattern sum scores (UPSS) and predominant echotexture nerve conduction study scores (NCSS) as well as Medical Research Council sum scores (MRCSS) and inflammatory neuropathy cause and treatment disability scores (INCAT) at baseline and after 12 months of standard treatment. We retrospectively correlated ultrasound morphology with nerve histology when available. 72/80 CIDP patients featured multifocal nerve enlargement, and 35/80 were therapy-naïve. At baseline, clinical scores correlated with NCSS (r 2  = 0.397 and r 2  = 0.443, p  50% of measured segments, possibly reflecting axonal degeneration; and 3) almost no enlargement, reflecting "burned-out" or "cured" disease without active inflammation. Clinical improvement after 12 months was best in patients with pattern 1 (up to 75% vs up to 43% in pattern 2/3, Fisher's exact test p < 0.05). Nerve ultrasound has additional value not only for diagnosis, but also for classification of disease state and may predict treatment response.

  2. Alemtuzumab in the treatment of IVIG-dependent chronic inflammatory demyelinating polyneuropathy.

    LENUS (Irish Health Repository)

    Marsh, E A

    2010-06-01

    Chronic inflammatory demyelinating polyneuropathy (CIDP) is an idiopathic immune mediated neuropathy causing demyelination and conduction block thought to occur as the result of an aberrant autoimmune response resulting in peripheral nerve inflammation mediated by T cells and humoral factors. Diagnosis commonly prompts initial treatment with steroids or intravenous immunoglobulin (IVIG) on which 5-35% subsequently become dependent to maintain function. Despite a number of small scale trials, the role for alternative long-term immunosuppression remains unclear. Alemtuzumab is a humanised monoclonal antibody targeting the CD52 antigen present on the surface of lymphocytes and monocytes. A single intravenous infusion results in rapid and profound lymphopoenia lasting >12 months. We report its use and clinical outcome in a small series of patients with severe IVIG-dependent CIDP. Seven patients (4 Males; 3 Females) who had failed to respond to conventional immunosuppression were treated in 5 centres receiving 9 courses of alemtuzumab (dose range 60-150 mg). Following treatment, mean monthly IVIG use fell 26% from 202 to 149 g and IVIG administration frequency from 22 to 136 days. Two patients had prolonged remission, two patients had a partial response and no clear benefit was observed in the remaining three patients (2 Males, 1 Females). Responding patients had a younger age at onset (19.5 years) and shorter disease duration than non-responders. Three patients developed autoimmune disease following treatment. Alemtuzumab may offer an alternative treatment for a subset of early onset IVIG dependent CIDP patients failing conventional immunosuppressive agents, but concerns about toxicity may limit its use.

  3. Atypical idiopathic inflammatory demyelinating lesions

    DEFF Research Database (Denmark)

    Wallner-Blazek, Mirja; Rovira, Alex; Fillipp, Massimo

    2013-01-01

    Atypical lesions of a presumably idiopathic inflammatory demyelinating origin present quite variably and may pose diagnostic problems. The subsequent clinical course is also uncertain. We, therefore, wanted to clarify if atypical idiopathic inflammatory demyelinating lesions (AIIDLs) can be class......Atypical lesions of a presumably idiopathic inflammatory demyelinating origin present quite variably and may pose diagnostic problems. The subsequent clinical course is also uncertain. We, therefore, wanted to clarify if atypical idiopathic inflammatory demyelinating lesions (AIIDLs) can...... be classified according to previously suggested radiologic characteristics and how this classification relates to prognosis. Searching the databases of eight tertiary referral centres we identified 90 adult patients (61 women, 29 men; mean age 34 years) with ≥1 AIIDL. We collected their demographic, clinical...

  4. Resistance training and aerobic training improve muscle strength and aerobic capacity in chronic inflammatory demyelinating polyneuropathy.

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    Markvardsen, Lars H; Overgaard, Kristian; Heje, Karen; Sindrup, Søren H; Christiansen, Ingelise; Vissing, John; Andersen, Henning

    2018-01-01

    We investigated the effects of aerobic and resistance exercise in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Eighteen CIDP patients treated with subcutaneous immunoglobulin performed 12 weeks of aerobic exercise and 12 weeks of resistance exercise after a run-in period of 12 weeks without exercise. Three times weekly the participants performed aerobic exercise on an ergometer bike or resistance exercise with unilateral training of knee and elbow flexion/extension. Primary outcomes were maximal oxygen consumption velocity (VO 2 -max) and maximal combined isokinetic muscle strength (cIKS) of knee and elbow flexion/extension. VO 2 -max and muscle strength were unchanged during run-in (-4.9% ± 10.3%, P = 0.80 and -3.7% ± 10.1%, P = 0.17, respectively). Aerobic exercise increased VO 2 -max by 11.0% ± 14.7% (P = 0.02). Resistance exercise resulted in an increase of 13.8% ± 16.0% (P = 0.0004) in cIKS. Aerobic exercise training and resistance exercise training improve fitness and strength in CIDP patients. Muscle Nerve 57: 70-76, 2018. © 2017 Wiley Periodicals, Inc.

  5. Long-Lasting Cranial Nerve III Palsy as a Presenting Feature of Chronic Inflammatory Demyelinating Polyneuropathy

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    Rossella Spataro

    2015-01-01

    Full Text Available We describe a patient with chronic inflammatory demyelinating polyneuropathy (CIDP in which an adduction deficit and ptosis in the left eye presented several years before the polyneuropathy. A 52-year-old man presented with a 14-year history of unremitting diplopia, adduction deficit, and ptosis in the left eye. At the age of 45 a mild bilateral foot drop and impaired sensation in the four limbs appeared, with these symptoms showing a progressive course. The diagnostic workup included EMG/ENG which demonstrated reduced conduction velocity with bilateral and symmetrical sensory and motor involvement. Cerebrospinal fluid studies revealed a cytoalbuminologic dissociation. A prolonged treatment with corticosteroids allowed a significant improvement of the limb weakness. Diplopia and ptosis remained unchanged. This unusual form of CIDP presented as a long-lasting isolated cranial nerve palsy. A diagnostic workup for CIDP should therefore be performed in those patients in which an isolated and unremitting cranial nerve palsy cannot be explained by common causes.

  6. Magnetic resonance imaging of the cauda equina in chronic inflammatory demyelinating polyneuropathy

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    A. F. Vasilenko

    2017-01-01

    Full Text Available Background. Chronic inflammatory demyelinating polyneuropathy (CIDP is a treatable disimmune neuropathy, which accurate diagnostics and treatment are essential to improve a long-lasting  prognosis and prevent invalidization. In atypical cases and  differential diagnosis extra investigations are needed, including neuroimaging.Objective. Evaluating the diagnostic role of the cauda equina magnetic resonance imaging (MRI in CIDP.Materials and methods. 8 patients with CIDP according to European Federation of Neurological Societies and Peripheral Nerve Society criteria were originally included in the main cohort: 6  patients with definitive CIDP, 1 patient – with possible CIDP; in 1  patient later mixed crioglobulinemia, associated with hepatitis C was  later diagnosed. MRI with contrast enhancement of the cauda equina was performed in all primary included patients in the main cohort  and in 8 controls with metabolic polyneuropathy. In 12 months MRI was repeated in the main cohort patients.Results. The enlargement of the nerve roots of the cauda equina and nodular hypertrophy was demonstrated in all CIDP patients, and in none of the control subjects. The extensiveness of qualitative  changes correlated with disease duration. All CIDP patients with root hypertrophy had gadolinium enhancement and its severity did not  correlate with disease activity. Contrast enhancement in roots of the  control group patients was explained by the medullary artery phenomenon.Conclusion. MRI of the cauda equina with contrast improves the diagnostic of CIDP, but does not depict the activity of the disease. MRI in CIDP is a promissing technique, requiring further investigation and standardization.

  7. Outcome in chronic inflammatory demyelinating polyneuropathy from a Malaysian centre over sixteen years.

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    Hiew, Fu Liong; Ong, Jun-Jean; Viswanathan, Shanthi; Puvanarajah, Santhi

    2018-04-01

    Long-term outcome in Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) is very limited, especially from Asian countries. We aimed to determine the outcome of our cohort of CIDP patients and to define the relevant clinical, electrophysiological and laboratory determinants of disease activity, progression and treatment response. We retrospectively reviewed records of 23 CIDP patients attending our Neurology service at Kuala Lumpur Hospital, Malaysia between January 2000 and December 2016. We analysed data on neurological deficits, electrophysiological and laboratory parameters to determine diagnostic characteristics, correlation with disease activity and clinical outcomes following treatment. Included were 15 (65%) males and 8 (35%) females with a mean age of 42.7 years (SD 14.4). Mean duration of follow-up visit was 66 months (range 6-134 months). The cohort consists of 19 classical (sensory-motor) CIDP and 4 MADSAM. Large majority of patients (66%) had either stable active disease (CDAS 3, 44%) or were in remission (CDAS class 2, 22%) following treatment with standard immunotherapies (Intravenous Immunoglobulins, steroids or immunosuppressants). The proportion of CIDP patients in each CDAS class was comparable to published cohorts from North America and Europe. Medical Research Council (MRC) sum score was the only clinical score that differed across CDAS classes (p = .010) with significant inverse correlation (Spearman's rho -0.664, p = .001). In conclusion, treatment outcomes of our CIDP cohort was comparable to those of published series. Further studies with larger cohort of patients from other parts of Asia are important to determine the long-term outcome of this heterogenous disease in this region. Copyright © 2018 Elsevier Ltd. All rights reserved.

  8. Fatigue, Pain, Anxiety and Depression in Guillain-Barré Syndrome and Chronic Inflammatory Demyelinating Polyradiculoneuropathy.

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    Merkies, Ingemar S J; Kieseier, Bernd C

    2016-01-01

    In the clinical evaluation of patients with Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), scant attention is paid to symptoms such as fatigue, pain and anxiety/depression. We aimed at addressing seminal studies that focused on the burden of these symptoms and their impact on quality of life (QoL) in these conditions. Fatigue, pain, and anxiety/depression are increasingly being recognized in patients with GBS and CIDP, although their pathophysiological provenance remains unknown. Fatigue and pain are significant in terms of prevalence and intensity, may be a presenting symptom, and can persist for years after apparent functional recovery, suggesting residual injury. Anxiety/depression has also been examined although studies are limited. Despite their negative impact on QoL, the long-term dynamics of these symptoms in patients with GBS and particularly CIDP receiving therapy in routine clinical practice have not been systematically evaluated. Such observations formed the basis for the ongoing (GAMEDIS) studies evaluating the effect of Gamunex on fatigue and depression in patients with CIDP, of which some preliminary data are presented. Strength and sensory deficits are the main areas of focus in patients with GBS and CIDP, but they do not explain the total reduction in QoL, suggesting the possible role of other complaints. A more comprehensive approach to patient care demands that factors such as pain, fatigue and anxiety/depression receive greater attention. The non-interventional GAMEDIS studies are expected to provide valuable insight into the long-term effectiveness of Gamunex in everyday practice. © 2016 S. Karger AG, Basel.

  9. A novel paraneoplastic syndrome with acquired lipodystrophy and chronic inflammatory demyelinating polyneuropathy in an adolescent male with craniopharyngioma.

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    Lockemer, Hillary Elizabeth; Sumpter, Kathryn Maria; Cope-Yokoyama, Sandy; Garg, Abhimanyu

    2018-03-28

    Acquired lipodystrophy, craniopharyngioma and chronic inflammatory demyelinating polyneuropathy (CIDP) are individually rare disorders, and have never before been reported in a single patient. A 15-year-7 month old Caucasian male presented with lower extremity weakness, frequent falls and abnormal fat distribution occurring over the previous 1 year. He was diagnosed with CIDP, craniopharyngioma and acquired lipodystrophy. The patient underwent tumor debulking and cranial irradiation for the craniopharyngioma, and received monthly intravenous immunoglobulin for the CIDP. The patient initially had some resolution of the lipodystrophy phenotype, but subsequently the abnormal fat distribution recurred and the patient developed additional systemic abnormalities, including mild pancytopenia and hepatic fibrosis. Our patient represents a novel association of acquired lipodystrophy, craniopharyngioma, and CIDP, possibly due to an as yet unidentified paraneoplastic autoantibody.

  10. Subcutaneous immunoglobulin as first-line therapy in treatment-naive patients with chronic inflammatory demyelinating polyneuropathy

    DEFF Research Database (Denmark)

    Markvardsen, L H; Sindrup, S H; Christiansen, I

    2017-01-01

    BACKGROUND AND PURPOSE: Subcutaneous immunoglobulin (SCIG) is effective as maintenance treatment in chronic inflammatory demyelinating polyneuropathy (CIDP). We investigated whether multiple subcutaneous infusions are as effective as conventional therapy with intravenous loading doses in treatment...... treatment arm and followed for a further 10 weeks. All participants were evaluated at weeks 0, 2, 5 and 10 during both therapies. Primary outcome was combined isokinetic muscle strength (cIKS). Secondary outcomes were disability, clinical evaluation of muscle strength and the performance of various function...... tests. RESULTS: All participants received both therapies, 14 completing the protocol. Overall, cIKS increased by 7.4 ± 14.5% (P = 0.0003) during SCIG and by 6.9 ± 16.8% (P = 0.002) during IVIG, the effect being similar (P = 0.80). Improvement of cIKS peaked 2 weeks after IVIG and 5 weeks after SCIG...

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

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

    2017-01-13

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a chronic progressive or relapsing and remitting disease that usually causes weakness and sensory loss. The symptoms are due to autoimmune inflammation of peripheral nerves. CIPD affects about 2 to 3 per 100,000 of the population. More than half of affected people cannot walk unaided when symptoms are at their worst. CIDP usually responds to treatments that reduce inflammation, but there is disagreement about which treatment is most effective. To summarise the evidence from Cochrane systematic reviews (CSRs) and non-Cochrane systematic reviews of any treatment for CIDP and to compare the effects of treatments. We considered all systematic reviews of randomised controlled trials (RCTs) of any treatment for any form of CIDP. We reported their primary outcomes, giving priority to change in disability after 12 months.Two overview authors independently identified published systematic reviews for inclusion and collected data. We reported the quality of evidence using GRADE criteria. Two other review authors independently checked review selection, data extraction and quality assessments.On 31 October 2016, we searched the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects (in theCochrane Library), MEDLINE, Embase, and CINAHL Plus for systematic reviews of CIDP. We supplemented the RCTs in the existing CSRs by searching on the same date for RCTs of any treatment of CIDP (including treatment of fatigue or pain in CIDP), in the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL Plus. Five CSRs met our inclusion criteria. We identified 23 randomised trials, of which 15 had been included in these CSRs. We were unable to compare treatments as originally planned, because outcomes and outcome intervals differed. CorticosteroidsIt is uncertain whether daily oral prednisone improved impairment compared to no treatment because the quality of the

  12. Anti-Ma2–associated limbic encephalitis with coexisting chronic inflammatory demyelinating polyneuropathy in a patient with non-Hodgkin lymphoma

    Science.gov (United States)

    Ju, Weina; Qi, Baochang; Wang, Xu; Yang, Yu

    2017-01-01

    Abstract Rationale: We report the rare case of a 74-year-old man with anti-Ma2–associated paraneoplastic neurologic syndrome (PNS), and review and analyze the clinical manifestations, diagnosis, and treatment of the disease. Patient concerns: The patient presented with a 5-month history of muscle weakness, progressive body aches, and weakness and numbness in both lower extremities. Before his hospitalization, he had experienced cognitive function decline; ptosis, inward gaze, and vertical gaze palsy in the right eye; and occasional visual hallucinations. Brain and spinal cord magnetic resonance imaging (MRI) yielded normal results. Anti-Ma2 antibodies were detected in both serum and cerebrospinal fluid. A 4-hour electroencephalogram showed irregular sharp slow waves and δ waves in the temporal region. Electromyography showed peripheral nerve demyelination. Positron-emission tomography/computed tomography (PET-CT) examination revealed hypermetabolism in the lymph nodes of the whole body. Biopsy of the lymph nodes showed non-Hodgkin lymphoma. Diagnosis: A clinical diagnosis of lymphoma and PNS was made. Interventions: The patient was treated with intravenous dexamethasone (15 mg/day) for 3 days. Lessons: We have presented a rare case of a PNS involving both the central and peripheral nervous systems. The clinical features of this case indicated anti-Ma2–associated encephalitis and chronic inflammatory demyelinating polyneuropathy. PET-CT played a critical role in enabling early diagnosis and prompt treatment in this case. PMID:28984777

  13. Anti-Ma2-associated limbic encephalitis with coexisting chronic inflammatory demyelinating polyneuropathy in a patient with non-Hodgkin lymphoma: A case report.

    Science.gov (United States)

    Ju, Weina; Qi, Baochang; Wang, Xu; Yang, Yu

    2017-10-01

    We report the rare case of a 74-year-old man with anti-Ma2-associated paraneoplastic neurologic syndrome (PNS), and review and analyze the clinical manifestations, diagnosis, and treatment of the disease. The patient presented with a 5-month history of muscle weakness, progressive body aches, and weakness and numbness in both lower extremities. Before his hospitalization, he had experienced cognitive function decline; ptosis, inward gaze, and vertical gaze palsy in the right eye; and occasional visual hallucinations. Brain and spinal cord magnetic resonance imaging (MRI) yielded normal results. Anti-Ma2 antibodies were detected in both serum and cerebrospinal fluid. A 4-hour electroencephalogram showed irregular sharp slow waves and δ waves in the temporal region. Electromyography showed peripheral nerve demyelination. Positron-emission tomography/computed tomography (PET-CT) examination revealed hypermetabolism in the lymph nodes of the whole body. Biopsy of the lymph nodes showed non-Hodgkin lymphoma. A clinical diagnosis of lymphoma and PNS was made. The patient was treated with intravenous dexamethasone (15 mg/day) for 3 days. We have presented a rare case of a PNS involving both the central and peripheral nervous systems. The clinical features of this case indicated anti-Ma2-associated encephalitis and chronic inflammatory demyelinating polyneuropathy. PET-CT played a critical role in enabling early diagnosis and prompt treatment in this case.

  14. Aggregation of MBP in chronic demyelination.

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    Frid, Kati; Einstein, Ofira; Friedman-Levi, Yael; Binyamin, Orli; Ben-Hur, Tamir; Gabizon, Ruth

    2015-07-01

    Misfolding of key disease proteins to an insoluble state is associated with most neurodegenerative conditions, such as prion, Parkinson, and Alzheimer's diseases. In this work, and by studying animal models of multiple sclerosis, we asked whether this is also the case for myelin basic protein (MBP) in the late and neurodegenerative phases of demyelinating diseases. To this effect, we tested whether MBP, an essential myelin component, present prion-like properties in animal models of MS, as is the case for Cuprizone-induced chronic demyelination or chronic phases of Experimental Autoimmune Encephalomyelitis (EAE). We show here that while total levels of MBP were not reduced following extensive demyelination, part of these molecules accumulated thereafter as aggregates inside oligodendrocytes or around neuronal cells. In chronic EAE, MBP precipitated concomitantly with Tau, a marker of diverse neurodegenerative conditions, including MS. Most important, analysis of fractions from Triton X-100 floatation gradients suggest that the lipid composition of brain membranes in chronic EAE differs significantly from that of naïve mice, an effect which may relate to oxidative insults and subsequently prevent the appropriate insertion and compaction of new MBP in the myelin sheath, thereby causing its misfolding and aggregation. Prion-like aggregation of MBP following chronic demyelination may result from an aberrant lipid composition accompanying this pathological status. Such aggregation of MBP may contribute to neuronal damage that occurs in the progressive phase of MS.

  15. Polirradiculoneuropatia desmielinizante inflamatória crônica: estudo de 18 pacientes Chronic inflammatory demyelinating polyradiculoneuropathy: study of 18 patients

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    Leandro C. Calia

    1997-01-01

    Full Text Available Neste estudo prospectivo, analisamos as características clínicas, evolução e resposta terapêutica de 18 pacientes com a forma idiopática de polirradiculoneuropatia desmielinizante inflamatória crônica, que foram acompanhados por período que variou de 4 a 127 meses. O sexo masculino predominou sobre o feminino (1,25:1 e a idade de início dos sintomas variou de 6 a 85 anos. Observamos a preponderância da forma de evolução progressiva (61,1% sobre a forma recidivante (38,9%, bem como a baixa ocorrência de fatores predisponentes (16,7%. Todos os pacientes apresentavam comprometimento sensitivo e motor, associado a hipo ou arreflexia, enquanto apenas três (16,7% apresentavam comprometimento de nervos cranianos. No exame do liquor, as taxas de proteínas estavam elevadas em 88,9% dos pacientes, com média de 203,4 mg/dl. A eletroneuromiografia mostrou alterações desmielinizantes em todos os pacientes, associadas a alterações axonais em 94,4% deles. Em todos os sete pacientes submetidos a biopsia de nervo sural encontramos alterações compatíveis com desmielinização/remielinização. A análise com imunofluorescência, realizada em três pacientes foi normal em um e evidenciou depósito de anticorpos anti-CD3 em dois e anti-HLA-Dr em um. Optamos pela prednisona como tratamento inicial em todos os pacientes, sendo mantida posteriormente em doses reduzidas e em dias alternados em 72,2% deles. Dois pacientes (11,1% estão assintomáticos mesmo após retirada total da medicação e introduzimos azatioprína, associada ou não ao corticóide, nos quatro pacientes com má resposta à prednisona. Até a última avaliação, 16 pacientes (88,9% evoluíram com melhora funcional.This is a prospective study that describes 18 patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP, idiopathic type. The patients have been followed for a period of 4 to 127 months. We evaluated the clinical characteristics, the evolution

  16. Diffusion tensor imaging can be used to detect lesions in peripheral nerves in patients with chronic inflammatory demyelinating polyneuropathy treated with subcutaneous immunoglobulin

    Energy Technology Data Exchange (ETDEWEB)

    Markvardsen, Lars H.; Andersen, Henning [Aarhus University Hospital, Department of Neurology, Aarhus C (Denmark); Vaeggemose, Michael [Aarhus University Hospital, Department of Neurology, Aarhus C (Denmark); Aarhus University Hospital, Department of Diagnostic Imaging: MR Research Centre, Aarhus (Denmark); Ringgaard, Steffen [Aarhus University Hospital, Department of Diagnostic Imaging: MR Research Centre, Aarhus (Denmark)

    2016-08-15

    Magnetic resonance imaging (MRI) with diffusion tensor imaging (DTI) has shown that fractional anisotropy (FA) is lower in peripheral nerves in chronic inflammatory demyelinating polyneuropathy (CIDP). We examined whether DTI correlates to muscle strength or impairment. MRI of sciatic and tibial nerves was performed on 3-T MR scanner by obtaining T2- and DTI-weighted sequences with fat saturation. On each slice of T2-weighted (T2w) and DTI, the tibial and sciatic nerves were segmented and served for calculation of signal intensity. On DTI images, pixel-by-pixel calculation of FA and apparent diffusion coefficient (ADC) was done. Muscle strength at knee and ankle was determined by isokinetic dynamometry and severity of CIDP by neuropathy impairment score (NIS). Fourteen CIDP patients treated with subcutaneous immunoglobulin were compared to gender- and age-matched controls. T2w values expressed as a nerve/muscle ratio (nT2w) were unchanged in CIDP versus controls 0.93 ± 0.21 versus 1.02 ± 0.21 (P = 0.10). FA values were lower in CIDP compared to controls 0.38 ± 0.07 versus 0.45 ± 0.05 (P < 0.0001), and ADC values were higher in CIDP versus controls 1735 ± 232 versus 1593 ± 116 x 10{sup -6} mm{sup 2}/s (P = 0.005). In CIDP, FA values correlated to clinical impairment (NIS) (r = -0.57, P = 0.03), but not to muscle strength. FA value in the sciatic nerve distinguishes CIDP from controls with a sensitivity and a specificity of 92.9 %. CIDP patients have unchanged nT2w values, lower FA values, and higher ADC values of sciatic and tibial nerves compared to controls. FA values correlated to NIS but were unrelated to muscle strength. DTI of sciatic nerves seems promising to differentiate CIDP from controls. (orig.)

  17. Inflammatory demyelinating pseudotumor with hemorrhage masquerading high grade cerebral neoplasm

    Directory of Open Access Journals (Sweden)

    Amit Agrawal

    2015-03-01

    Full Text Available Demyelinating pseudotumors are rare, benign, solitary intracranial space occupying lesions which masquerade cerebral neoplasms. Contrast MRI shows open ring enhancement which is fairly specific for this entity. Advanced MRI techniques like MR spectroscopy and magnetizing transfer techniques can help differentiating these lesions. NAA/Cr ratio is significantly elevated in central regions of demyelinating pseudotumors than in gliomas and other lesions. Presence of abundant foamy macrophages, lymphoid inflammatory infiltrates around blood vessels, sheets of gemistocytic astrocytes with well-developed processes, well defined border of the lesion absence of neovascularity and necrosis should help us diagnose demyelinating pseudotumor fairly confidently on histopathology.

  18. A Case Of Infectious Mononucleosis With Acute Inflammatory Demyelinating Polyradiculoneuropathy

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    Somani S K

    2003-01-01

    Full Text Available We report a case of Acute inflammatory demyelinating polyradiculo neuropathy (AIDP, following infectious mononucleosis. A 12 year old girl presented with acute flaccid quadriplegia with bilateral cervical lymphadenopathy and enlarged tonsils six weeks after a febrile illness. Cerebrospinal fluid revealed albuminocytological dissociation and electrophysiology showed evidence of axonal-demyelinating polyradiculoneuropathy. Heterophile antibody test was positive and lymph node biopsy showed non -specific reactive hyperplasia. She was managed conservatively with good outcome.

  19. Astrogliosis During Acute and Chronic Cuprizone Demyelination and Implications for Remyelination

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    Norah Hibbits

    2012-10-01

    Full Text Available In multiple sclerosis, microglia/macrophage activation and astrocyte reactivity are important components of the lesion environment that can impact remyelination. The current study characterizes these glial populations relative to expression of candidate regulatory molecules in cuprizone demyelinated corpus callosum. Importantly, periods of recovery after acute or chronic cuprizone demyelination are examined to compare conditions of efficient versus limited remyelination, respectively. Microglial activation attenuates after early demyelination. In contrast, astrocyte reactivity persists throughout demyelination and a 6-week recovery period following either acute or chronic demyelination. This astrocyte reaction is characterized by (a early proliferation, (b increased expression of GFAP (glial fibrillary acidic protein, Vim (vimentin, Fn1 (fibronectin and CSPGs (chondroitin sulphate proteoglycans and (c elaboration of a dense network of processes. Glial processes elongated in the axonal plane persist throughout lesion areas during both the robust remyelination that follows acute demyelination and the partial remyelination that follows chronic demyelination. However, prolonged astrocyte reactivity with chronic cuprizone treatment does not progress to barrier formation, i.e. dense compaction of astrocyte processes to wall off the lesion area. Multiple candidate growth factors and inflammatory signals in the lesion environment show strong correlations with GFAP across the acute cuprizone demyelination and recovery time course, yet there is more divergence across the progression of chronic cuprizone demyelination and recovery. However, differential glial scar formation does not appear to be responsible for differential remyelination during recovery in the cuprizone model. The astrocyte phenotype and lesion characteristics in this demyelination model inform studies to identify triggers of non-remyelinating sclerosis in chronic multiple sclerosis

  20. The frequencies of Killer immunoglobulin-like receptors and their HLA ligands in chronic inflammatory demyelinating polyradiculoneuropathy are similar to those in Guillian Barre syndrome but differ from those of controls, suggesting a role for NK cells in pathogenesis.

    Science.gov (United States)

    Blum, Stefan; Csurhes, Peter; McCombe, Pamela

    2015-08-15

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired inflammatory neuropathy, which has similar clinical and pathological features to Guillain-Barré Syndrome (GBS), but differs in time course. We investigated the frequency of genes encoding Killer immunoglobulin-like receptors and their HLA ligands in subjects with CIDP, in subjects with GBS and in healthy controls. There were no differences in KIR gene frequency among the 3 groups. The gene frequencies for HLA-B Bw4-I were significantly greater in CIDP than HC, but did not differ from GBS. The frequency of the combination of 3DL1/HLA-B Bw4I was greater in CIDP than HC, but did not differ from that of GBS. These data raise the possibility of NK cell function being an important factor in the pathogenesis of CIDP. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Interleukin-10 overexpression promotes Fas-ligand-dependent chronic macrophage-mediated demyelinating polyneuropathy.

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    Dru S Dace

    Full Text Available BACKGROUND: Demyelinating polyneuropathy is a debilitating, poorly understood disease that can exist in acute (Guillain-Barré syndrome or chronic forms. Interleukin-10 (IL-10, although traditionally considered an anti-inflammatory cytokine, has also been implicated in promoting abnormal angiogenesis in the eye and in the pathobiology of autoimmune diseases such as lupus and encephalomyelitis. PRINCIPAL FINDINGS: Overexpression of IL-10 in a transgenic mouse model leads to macrophage-mediated demyelinating polyneuropathy. IL-10 upregulates ICAM-1 within neural tissues, promoting massive macrophage influx, inflammation-induced demyelination, and subsequent loss of neural tissue resulting in muscle weakness and paralysis. The primary insult is to perineural myelin followed by secondary axonal loss. Infiltrating macrophages within the peripheral nerves demonstrate a highly pro-inflammatory signature. Macrophages are central players in the pathophysiology, as in vivo depletion of macrophages using clodronate liposomes reverses the phenotype, including progressive nerve loss and paralysis. Macrophage-mediate demyelination is dependent on Fas-ligand (FasL-mediated Schwann cell death. SIGNIFICANCE: These findings mimic the human disease chronic idiopathic demyelinating polyneuropathy (CIDP and may also promote further understanding of the pathobiology of related conditions such as acute idiopathic demyelinating polyneuropathy (AIDP or Guillain-Barré syndrome.

  2. Clinical Significance of A Waves in Acute Inflammatory Demyelinating Polyradiculoneuropathy.

    Science.gov (United States)

    Lakshminarasimhan, Sindhuja; Venkatraman, Chandramouleeswaran; Vellaichamy, Kannan; Ranganathan, Lakshminarasimhan

    2018-05-25

    A wave is a late response recognized during recording of F waves. Though they might be seen in healthy subjects, their presence assumes significance in a patient presenting with polyradiculoneuropathy. In this prospective study, 75 patients with acute inflammatory demyelinating polyradiculoneuropathy (AIDP) were enrolled. They were divided into two groups based on the presence or absence of A waves. Clinical features, electrophysiological parameters and extent of clinical recovery in short-term follow-up were analyzed. A waves were present in 49 out of 75 patients (65%). Most common pattern observed was multiple A waves. Prevalence of A waves was more in lower limb nerves than upper limb nerves. Occurrence of A waves correlated with the presence of conduction block. Patients with A waves had higher Hughes grade (P = 0.003) and lower Medical Research Council sum score at 6 weeks of follow-up (P = 0.04) as compared to patients without A waves. A waves are common in acute inflammatory demyelinating polyradiculoneuropathy form of Guillain Barre syndrome and are considered as a marker of demyelination. Long-term follow-up studies are required to ascertain their significance in prognostication and assessing recovery.

  3. Citation classics in central nervous system inflammatory demyelinating disease.

    Science.gov (United States)

    Kim, Jee-Eun; Park, Kang M; Kim, Yerim; Yoon, Dae Y; Bae, Jong S

    2017-06-01

    To identify and analyze the characteristics of the most influential articles about central nervous system (CNS) inflammatory demyelinating disease. The Institute for Scientific Information (ISI) Web of Science database and the 2014 Journal Citation Reports Science Edition were used to retrieve the top 100 cited articles on CNS inflammatory demyelinating disease. The citation numbers, journals, years of publication, authorships, article types, subjects and main issues were analyzed. For neuromyelitis optica (NMO), articles that were cited more than 100 times were regarded as a citation classic and described separately. The top 100 cited articles were published between 1972 and 2011 in 13 journals. The highest number of articles ( n  = 24) was published in Brain, followed by The New England Journal of Medicine ( n  = 21). The average number of citations was 664 (range 330-3,897), and 64% of the articles were from the United States and the United Kingdom. The majority of the top 100 cited articles were related to multiple sclerosis ( n  = 87), and only a few articles reported on other topics such as NMO ( n  = 9), acute disseminated encephalomyelitis ( n  = 2) and optic neuritis ( n  = 2). Among the top 100 cited articles, 77% were original articles. Forty-one citation classics were found for NMO. Our study provides a historical perspective on the research progress on CNS inflammatory demyelinating disease and may serve as a guide for important advances and trends in the field for associated researchers.

  4. Acute Inflammatory Demyelinating Neuropathy : Immunoglobulin And Immune Complex Profile

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    Shripad A

    2003-01-01

    Full Text Available Serum immunoglobulins (IgG, IgA and IgM and immune complexes IgG (IcG were measured in 58 cases of acute inflammatory demyelinating neuropathy, popularly known as Guillian Barre′ syndrome, and in 30 healthy controls using single radial immunodiffusion assay. Immunoglobulin and immune complex levels were significantly elevated in patients as compared to controls. The increased levels of immunoglobulins and immune complexes may contribute to the pathogenesis of the disease and provide rationale for therapeutic plasmapheresis.

  5. Interferon beta-1a in chronic inflammatory demyelinating polyneuropathy: case report Interferon beta en polineuropatía crónica inflamatoria desmienlinizante: caso clínico

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    Andrés Maria Villa

    2004-09-01

    Full Text Available Chronic inflammatory demyelinating polyneuropathy (CIDP is an acquired immune-mediated neuropathy. It presents with a course of progression which may be slow and steady or step-wise or relapsing. Sensory ataxic polyneuropathy may be the only clinical manifestation of this disease. Treatment with interferon beta1a (INF beta1a has been tried with different results in patients who were refractory to other, more conventional, immunomodulatory therapies. Here we report on a patient who had a relapsing form of pure sensory ataxic CIDP and who failed to respond to intravenous human immunoglobulin. He was put on INF beta1a for 3 years. During this period he suffered no relapses while his condition stabilized.La polineuropatía crónica inflamatoria desmielinizante (PCID es una neuropatía inmuno-mediada, que presenta un curso clínico primariamente progresivo o en forma de recaídas. Las manifestaciones sensoriales pueden ser su unica forma de expresión clínica. El tratamiento con interferon beta 1a (IFN beta1a ha sido ensayado en varias oportunidades, con diferentes respuestas terapéuticas, en pacientes refractarios a las terapias inmunomoduladoras convencionales. Nosotros comunicamos un paciente con una forma ataxica recurrente de PCID, que no respondió al tratamiento con inmunoglobulina endovenosa. Posteriormente fue tratado con IFN beta 1 a por tres años. Durante el período de seguimiento no mostró nuevas recaídas y su cuadro neurológico se estabilizó.

  6. Diagnostic value of the near-nerve needle sensory nerve conduction in sensory inflammatory demyelinating polyneuropathy.

    Science.gov (United States)

    Odabasi, Zeki; Oh, Shin J

    2018-03-01

    In this study we report the diagnostic value of the near-nerve needle sensory nerve conduction study (NNN-SNCS) in sensory inflammatory demyelinating polyneuropathy (IDP) in which the routine nerve conduction study was normal or non-diagnostic. The NNN-SNCS was performed to identify demyelination in the plantar nerves in 14 patients and in the median or ulnar nerve in 2 patients with sensory IDP. In 16 patients with sensory IDP, routine NCSs were either normal or non-diagnostic for demyelination. Demyelination was identified by NNN-SNCS by dispersion and/or slow nerve conduction velocity (NCV) below the demyelination marker. Immunotherapy was initiated in 11 patients, 10 of whom improved or remained stable. NNN-SNCS played an essential role in identifying demyelinaton in 16 patients with sensory IDP, leading to proper treatment. Muscle Nerve 57: 414-418, 2018. © 2017 Wiley Periodicals, Inc.

  7. Idiopathic inflammatory-demyelinating diseases of the central nervous system

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    Rovira Canellas, A. [Vall d' Hebron University Hospital, Magnetic Resonance Unit (I.D.I.), Department of Radiology, Barcelona (Spain); Rovira Gols, A. [Parc Tauli University Institute - UAB, UDIAT, Diagnostic Centre, Sabadell (Spain); Rio Izquierdo, J.; Tintore Subirana, M.; Montalban Gairin, X. [Vall d' Hebron University Hospital, Neuroimmunology Unit, Department of Neurology, Barcelona (Spain)

    2007-05-15

    Idiopathic inflammatory-demyelinating diseases (IIDDs) include a broad spectrum of central nervous system disorders that can usually be differentiated on the basis of clinical, imaging, laboratory and pathological findings. However, there can be a considerable overlap between at least some of these disorders, leading to misdiagnoses or diagnostic uncertainty. The relapsing-remitting and secondary progressive forms of multiple sclerosis (MS) are the most common IIDDs. Other MS phenotypes include those with a progressive course from onset (primary progressive and progressive relapsing) or with a benign course continuing for years after onset (benign MS). Uncommon forms of IIDDs can be classified clinically into: (1) fulminant or acute IIDDs, such as the Marburg variant of MS, Balo's concentric sclerosis, Schilder's disease, and acute disseminated encephalomyelitis; (2) monosymptomatic IIDDs, such as those involving the spinal cord (transverse myelitis), optic nerve (optic neuritis) or brainstem and cerebellum; and (3) IIDDs with a restricted topographical distribution, including Devic's neuromyelitis optica, recurrent optic neuritis and relapsing transverse myelitis. Other forms of IIDD, which are classified clinically and radiologically as pseudotumoral, can have different forms of presentation and clinical courses. Although some of these uncommon IIDDs are variants of MS, others probably correspond to different entities. MR imaging of the brain and spine is the imaging technique of choice for diagnosing these disorders, and together with the clinical and laboratory findings can accurately classify them. Precise classification of these disorders may have relevant prognostic and treatment implications, and might be helpful in distinguishing them from tumoral or infectious lesions, avoiding unnecessary aggressive diagnostic or therapeutic procedures. (orig.)

  8. Idiopathic inflammatory-demyelinating diseases of the central nervous system

    International Nuclear Information System (INIS)

    Rovira Canellas, A.; Rovira Gols, A.; Rio Izquierdo, J.; Tintore Subirana, M.; Montalban Gairin, X.

    2007-01-01

    Idiopathic inflammatory-demyelinating diseases (IIDDs) include a broad spectrum of central nervous system disorders that can usually be differentiated on the basis of clinical, imaging, laboratory and pathological findings. However, there can be a considerable overlap between at least some of these disorders, leading to misdiagnoses or diagnostic uncertainty. The relapsing-remitting and secondary progressive forms of multiple sclerosis (MS) are the most common IIDDs. Other MS phenotypes include those with a progressive course from onset (primary progressive and progressive relapsing) or with a benign course continuing for years after onset (benign MS). Uncommon forms of IIDDs can be classified clinically into: (1) fulminant or acute IIDDs, such as the Marburg variant of MS, Balo's concentric sclerosis, Schilder's disease, and acute disseminated encephalomyelitis; (2) monosymptomatic IIDDs, such as those involving the spinal cord (transverse myelitis), optic nerve (optic neuritis) or brainstem and cerebellum; and (3) IIDDs with a restricted topographical distribution, including Devic's neuromyelitis optica, recurrent optic neuritis and relapsing transverse myelitis. Other forms of IIDD, which are classified clinically and radiologically as pseudotumoral, can have different forms of presentation and clinical courses. Although some of these uncommon IIDDs are variants of MS, others probably correspond to different entities. MR imaging of the brain and spine is the imaging technique of choice for diagnosing these disorders, and together with the clinical and laboratory findings can accurately classify them. Precise classification of these disorders may have relevant prognostic and treatment implications, and might be helpful in distinguishing them from tumoral or infectious lesions, avoiding unnecessary aggressive diagnostic or therapeutic procedures. (orig.)

  9. Human immunodeficiency virus seroconversion presenting with acute inflammatory demyelinating polyneuropathy: a case report

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    Sloan Derek J

    2008-12-01

    Full Text Available Abstract Introduction Acute Human Immunodeficiency Virus infection is associated with a range of neurological conditions. Guillain-Barré syndrome is a rare presentation; acute inflammatory demyelinating polyneuropathy is the commonest form of Guillain-Barré syndrome. Acute inflammatory demyelinating polyneuropathy has occasionally been reported in acute Immunodeficiency Virus infection but little data exists on frequency, management and outcome. Case presentation We describe an episode of Guillain-Barré syndrome presenting as acute inflammatory demyelinating polyneuropathy in a 30-year-old man testing positive for Immunodeficiency Virus, probably during acute seroconversion. Clinical suspicion was confirmed by cerebrospinal fluid analysis and nerve conduction studies. Rapid clinical deterioration prompted intravenous immunoglobulin therapy and early commencement of highly active anti-retroviral therapy. All symptoms resolved within nine weeks. Conclusion Unusual neurological presentations in previously fit patients are an appropriate indication for Immunodeficiency-Virus testing. Highly active anti-retroviral therapy with adequate penetration of the central nervous system should be considered as an early intervention, alongside conventional therapies such as intravenous immunoglobulin.

  10. CD8+ T cells in inflammatory demyelinating disease

    DEFF Research Database (Denmark)

    Weiss, Hanne A; Millward, Jason M; Owens, Trevor

    2007-01-01

    We review the contribution made by CD8+ T cells to inflammation in the central nervous system (CNS) in Multiple Sclerosis (MS), and discuss their role in the animal model Experimental Autoimmune Encephalomyelitis (EAE). We show that the inflammatory cytokines interferon-gamma and interleukin-17...... are differentially regulated in CNS-infiltrating CD4+ and CD8+ T cells in EAE, and that CD8+ T cells regulate disease. In MS, CD8+ T cells appear to play a role in promotion of disease, so cytokine regulation is likely different in CD8+ T cells in MS and EAE...

  11. Autoimmune Demyelinating Polyneuropathy as a Manifestation of Chronic Graft-versus-Host Disease after Adult Cord Blood Transplantation in a Patient with Chronic Lymphocytic Leukemia

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    Fredrick Hogan

    2014-01-01

    Full Text Available Immune mediated demyelinating disease after allogeneic stem cell transplantation is a rare entity with unclear etiology. Acute inflammatory demyelinating polyneuropathy (AIDP has been reported after related and adult unrelated allogeneic stem cell transplantation but no such case has been reported after unrelated cord blood transplantation. We hereby present the first case of AIDP after double umbilical cord blood transplantation (DUCBT. A 55-year-old man with chronic lymphocytic leukemia (CLL received a cord blood transplant for relapsed refractory disease with high risk cytogenetics. On day 221, patient presented with skin rash, tingling in both lower extremites, and ascending paralysis that progressed rapidly over the course of 2 days. The workup resulted in a diagnosis of AIDP and administration of intravenous immunoglobulins plus steroids was initiated. Motor and sensory powers were fully recovered and his chronic GVHD was managed for several months with single agent sirolimus.

  12. Interferon-gamma in progression to chronic demyelination and neurological deficit following acute EAE

    DEFF Research Database (Denmark)

    Renno, T; Taupin, V; Bourbonnière, L

    1998-01-01

    The cytokine interferon-gamma (IFNgamma) is implicated in the induction of acute CNS inflammation, but it is less clear what role if any IFNgamma plays in progression to chronic demyelination and neurological deficit. To address this issue, we have expressed IFNgamma in myelinating oligodendrocytes....... In contrast to control mice, which remit from EAE with resolution of glial reactivity and leukocytic infiltration, transgenics showed chronic neurological deficits. While activated microglia/macrophages persisted in demyelinating lesions for over 100 days, CD4(+) T lymphocytes were no longer present in CNS...

  13. Diagnostic transcranial magnetic stimulation in children with acute inflammatory demyelinating polyneuropathy

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    V. B. Voitenkov

    2016-01-01

    Full Text Available Objective of our work was to evaluate MEPs characteristics in children with acute inflammatory demyelinating polyneuropathy and evaluate usefulness of TMS as an additional diagnostic method in this disorder.Methods. 20 healthy children (7–14 years old, average 12 years, 7 females, 13 males without any signs of neurological disorders were enrolled as controls and 37 patients (8–13 years old, average 11 years, 19 females, 18 males with AIDP were enrolled as the main group. EMG and TMS were performed on 3–7 day from the onset of the first symptoms. Cortical and lumbar MEP`s latencies, shapes and amplitudes and CMCT were averaged and analyzed.Results. Significant differences between children with AIDP and controls on latencies of both cortical and lumbar MEPs were registered. Cortical MEPs shapes were disperse in 100% of the cases, and lumbar MEPs were disperse in 57% of the cases. Amplitudes changes for both lumbar and cortical MEPs were not significant.Conclusions. Diagnostic transcranial magnetic stimulation on the early stage of the acute demyelinating polyneuropathy in children may be implemented as the additional tool. Main finding in this population is lengthening of the latency of cortical and lumbar motor evoked potentials. Disperse shape of the lumbar MEPs may also be used as the early sign of the acute demyelization of the peripheral nerves.

  14. Acute paretic syndrome in juvenile White Leghorn chickens resembles late stages of acute inflammatory demyelinating polyneuropathies in humans

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    Preisinger Rudolf

    2010-01-01

    Full Text Available Abstract Background Sudden limb paresis is a common problem in White Leghorn flocks, affecting about 1% of the chicken population before achievement of sexual maturity. Previously, a similar clinical syndrome has been reported as being caused by inflammatory demyelination of peripheral nerve fibres. Here, we investigated in detail the immunopathology of this paretic syndrome and its possible resemblance to human neuropathies. Methods Neurologically affected chickens and control animals from one single flock underwent clinical and neuropathological examination. Peripheral nervous system (PNS alterations were characterised using standard morphological techniques, including nerve fibre teasing and transmission electron microscopy. Infiltrating cells were phenotyped immunohistologically and quantified by flow cytometry. The cytokine expression pattern was assessed by quantitative real-time PCR (qRT-PCR. These investigations were accomplished by MHC genotyping and a PCR screen for Marek's disease virus (MDV. Results Spontaneous paresis of White Leghorns is caused by cell-mediated, inflammatory demyelination affecting multiple cranial and spinal nerves and nerve roots with a proximodistal tapering. Clinical manifestation coincides with the employment of humoral immune mechanisms, enrolling plasma cell recruitment, deposition of myelin-bound IgG and antibody-dependent macrophageal myelin-stripping. Disease development was significantly linked to a 539 bp microsatellite in MHC locus LEI0258. An aetiological role for MDV was excluded. Conclusions The paretic phase of avian inflammatory demyelinating polyradiculoneuritis immunobiologically resembles the late-acute disease stages of human acute inflammatory demyelinating polyneuropathy, and is characterised by a Th1-to-Th2 shift.

  15. IL-1 signal affects both protection and pathogenesis of virus-induced chronic CNS demyelinating disease

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    Kim Byung S

    2012-09-01

    Full Text Available Abstract Background Theiler’s virus infection induces chronic demyelinating disease in mice and has been investigated as an infectious model for multiple sclerosis (MS. IL-1 plays an important role in the pathogenesis of both the autoimmune disease model (EAE and this viral model for MS. However, IL-1 is known to play an important protective role against certain viral infections. Therefore, it is unclear whether IL-1-mediated signaling plays a protective or pathogenic role in the development of TMEV-induced demyelinating disease. Methods Female C57BL/6 mice and B6.129S7-Il1r1tm1Imx/J mice (IL-1R KO were infected with Theiler’s murine encephalomyelitis virus (1 x 106 PFU. Differences in the development of demyelinating disease and changes in the histopathology were compared. Viral persistence, cytokine production, and immune responses in the CNS of infected mice were analyzed using quantitative PCR, ELISA, and flow cytometry. Results Administration of IL-1β, thereby rending resistant B6 mice susceptible to TMEV-induced demyelinating disease, induced a high level of Th17 response. Interestingly, infection of TMEV into IL-1R-deficient resistant C57BL/6 (B6 mice also induced TMEV-induced demyelinating disease. High viral persistence was found in the late stage of viral infection in IL-1R-deficient mice, although there were few differences in the initial anti-viral immune responses and viral persistent levels between the WT B6 and IL-1R-deficiecent mice. The initial type I IFN responses and the expression of PDL-1 and Tim-3 were higher in the CNS of TMEV-infected IL-1R-deficient mice, leading to deficiencies in T cell function that permit viral persistence. Conclusions These results suggest that the presence of high IL-1 level exerts the pathogenic role by elevating pathogenic Th17 responses, whereas the lack of IL-1 signals promotes viral persistence in the spinal cord due to insufficient T cell activation by elevating the production of

  16. Sildenafil (Viagra Protective Effects on Neuroinflammation: The Role of iNOS/NO System in an Inflammatory Demyelination Model

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    Catarina Raposo

    2013-01-01

    Full Text Available We recently demonstrated that sildenafil reduces the expression of cytokines, COX-2, and GFAP in a demyelinating model induced in wild-type (WT mice. Herein, the understandings of the neuroprotective effect of sildenafil and the mediation of iNOS/NO system on inflammatory demyelination induced by cuprizone were investigated. The cerebella of iNOS−/− mice were examined after four weeks of treatment with cuprizone alone or combined with sildenafil. Cuprizone increased GFAP, Iba-1, TNF-α, COX-2, IL-1β, and IFN-γ expression, decreased expression of glutathione S-transferase pi (GSTpi, and damaged myelin in iNOS−/− mice. Sildenafil reduced Iba-1, IFN-γ, and IL-1β levels but had no effect on the expression of GFAP, TNF-α, and COX-2 compared to the cuprizone group. Sildenafil elevated GSTpi levels and improved the myelin structure/ultrastructure. iNOS−/− mice suffered from severe inflammation following treatment with cuprizone, while WT mice had milder inflammation, as found in the previous study. It is possible that inflammatory regulation through iNOS-feedback is absent in iNOS−/− mice, making them more susceptible to inflammation. Sildenafil has at least a partial anti-inflammatory effect through iNOS inhibition, as its effect on iNOS−/− mice was limited. Further studies are required to explain the underlying mechanism of the sildenafil effects.

  17. Occipital neuralgia associates with high cervical spinal cord lesions in idiopathic inflammatory demyelinating disease.

    Science.gov (United States)

    Kissoon, Narayan R; Watson, James C; Boes, Christopher J; Kantarci, Orhun H

    2018-01-01

    Background The association of trigeminal neuralgia with pontine lesions has been well documented in multiple sclerosis, and we tested the hypothesis that occipital neuralgia in multiple sclerosis is associated with high cervical spinal cord lesions. Methods We retrospectively reviewed the records of 29 patients diagnosed with both occipital neuralgia and demyelinating disease by a neurologist from January 2001 to December 2014. We collected data on demographics, clinical findings, presence of C2-3 demyelinating lesions, and treatment responses. Results The patients with both occipital neuralgia and multiple sclerosis were typically female (76%) and had a later onset (age > 40) of occipital neuralgia (72%). Eighteen patients (64%) had the presence of C2-3 lesions and the majority had unilateral symptoms (83%) or episodic pain (78%). All patients with documented sensory loss (3/3) had C2-3 lesions. Most patients with progressive multiple sclerosis (6/8) had C2-3 lesions. Of the eight patients with C2-3 lesions and imaging at onset of occipital neuralgia, five (62.5%) had evidence of active demyelination. None of the patients with progressive multiple sclerosis (3/3) responded to occipital nerve blocks or high dose intravenous steroids, whereas all of the other phenotypes with long term follow-up (eight patients) had good responses. Conclusions A cervical spine MRI should be considered in all patients presenting with occipital neuralgia. In patients with multiple sclerosis, clinical features in occipital neuralgia that were predictive of the presence of a C2-3 lesion were unilateral episodic symptoms, sensory loss, later onset of occipital neuralgia, and progressive multiple sclerosis phenotype. Clinical phenotype predicted response to treatment.

  18. Patient with neuromyelitis optica and inflammatory demyelinating lesions comprising whole spinal cord from C2 level till conus: case report

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    Pavlisa Goran

    2009-10-01

    Full Text Available Abstract Background Neuromyelitis optica (NMO is an idiopathic, severe, inflammatory demyelinating disease of the central nervous system, that causes severe optic neuritis and myelitis attacks. Early discrimination between multiple sclerosis (MS and NMO is important, as optimum treatment for both diseases may differ considerably. Case Presentation We report a case of a patient who initially presented as longitudinally extensive transverse myelitis (LETM, having spastic upper extremities diparesis and spastic paraplegia, C2/C3 sensory level and urinary incontinence, as well as extensive inflammatory spinal cord lesions from C2 level to conus. After 5 months the patient had another attack of transverse myelitis, had electrophysiological findings consistent with optic neuritis, was seropositive for NMO-IgG (aquaporin-4 IgG and thus fulfilled NMO diagnostic criteria. Following treatment of disease attacks with pulse corticosteroid therapy and intravenous immunoglobulins, we included oral azathioprine in a combination with oral prednisone in the therapy. Since there was no significant clinical improvement, we decided to use cyclophosphamide therapy, which resulted in good clinical improvement and gradual decrease of cord swelling. Conclusion In this NMO case report we wanted to emphasize the extensiveness of inflammatory spinal cord changes in our patient, from C2 level to conus. In the conclusion it is important to say that accurate, early diagnosis and distinction from MS is critical to facilitate initiation of immunosuppressive therapy for attack prevention.

  19. Standing postural reaction to visual and proprioceptive stimulation in chronic acquired demyelinating polyneuropathy.

    Science.gov (United States)

    Provost, Clement P; Tasseel-Ponche, Sophie; Lozeron, Pierre; Piccinini, Giulia; Quintaine, Victorine; Arnulf, Bertrand; Kubis, Nathalie; Yelnik, Alain P

    2018-02-28

    To investigate the weight of visual and proprioceptive inputs, measured indirectly in standing position control, in patients with chronic acquired demyelinating polyneuropathy (CADP). Prospective case study. Twenty-five patients with CADP and 25 healthy controls. Posture was recorded on a double force platform. Stimulations were optokinetic (60°/s) for visual input and vibration (50 Hz) for proprioceptive input. Visual stimulation involved 4 tests (upward, downward, rightward and leftward) and proprioceptive stimulation 2 tests (triceps surae and tibialis anterior). A composite score, previously published and slightly modified, was used for the recorded postural signals from the different stimulations. Despite their sensitivity deficits, patients with CADP were more sensitive to proprioceptive stimuli than were healthy controls (mean composite score 13.9 ((standard deviation; SD) 4.8) vs 18.4 (SD 4.8), p = 0.002). As expected, they were also more sensitive to visual stimuli (mean composite score 10.5 (SD 8.7) vs 22.9 (SD 7.5), p <0.0001). These results encourage balance rehabilitation of patients with CADP, aimed at promoting the use of proprioceptive information, thereby reducing too-early development of visual compensation while proprioception is still available.

  20. Standing postural reaction to visual and proprioceptive stimulation in chronic acquired demyelinating polyneuropathy

    Directory of Open Access Journals (Sweden)

    Clement P. Provost

    2018-01-01

    Full Text Available Objective: To investigate the weight of visual and proprioceptive inputs, measured indirectly in standing position control, in patients with chronic acquired demyelinating polyneuropathy (CADP. Design: Prospective case study. Subjects: Twenty-five patients with CADP and 25 healthy controls. Methods: Posture was recorded on a double force platform. Stimulations were optokinetic (60°/s for visual input and vibration (50 Hz for proprioceptive input. Visual stimulation involved 4 tests (upward, downward, rightward and leftward and proprioceptive stimulation 2 tests (triceps surae and tibialis anterior. A composite score, previously published and slightly modified, was used for the recorded postural signals from the different stimulations. Results: Despite their sensitivity deficits, patients with CADP were more sensitive to proprioceptive stimuli than were healthy controls (mean composite score 13.9 ((standard deviation; SD 4.8 vs 18.4 (SD 4.8, p = 0.002. As expected, they were also more sensitive to visual stimuli (mean composite score 10.5 (SD 8.7 vs 22.9 (SD 7.5, p< 0.0001. Conclusion: These results encourage balance rehabilitation of patients with CADP, aimed at promoting the use of proprioceptive information, thereby reducing too-early development of visual compensation while proprioception is still available.

  1. Disease Type- and Status-Specific Alteration of CSF Metabolome Coordinated with Clinical Parameters in Inflammatory Demyelinating Diseases of CNS.

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    Soo Jin Park

    Full Text Available Central nervous system (CNS inflammatory demyelinating diseases (IDDs are a group of disorders with different aetiologies, characterized by inflammatory lesions. These disorders include multiple sclerosis (MS, neuromyelitis optica spectrum disorder (NMOSD, and idiopathic transverse myelitis (ITM. Differential diagnosis of the CNS IDDs still remains challenging due to frequent overlap of clinical and radiological manifestation, leading to increased demands for new biomarker discovery. Since cerebrospinal fluid (CSF metabolites may reflect the status of CNS tissues and provide an interfacial linkage between blood and CNS tissues, we explored multi-component biomarker for different IDDs from CSF samples using gas chromatography mass spectrometry-based metabolite profiling coupled to multiplex bioinformatics approach. We successfully constructed the single model with multiple metabolite variables in coordinated regression with clinical characteristics, expanded disability status scale, oligoclonal bands, and protein levels. The multi-composite biomarker simultaneously discriminated four different immune statuses (a total of 145 samples; 54 MS, 49 NMOSD, 30 ITM, and 12 normal controls. Furthermore, systematic characterization of transitional metabolic modulation identified relapse-associated metabolites and proposed insights into the disease network underlying type-specific metabolic dysfunctionality. The comparative analysis revealed the lipids, 1-monopalmitin and 1-monostearin were common indicative for MS, NMOSD, and ITM whereas fatty acids were specific for the relapse identified in all types of IDDs.

  2. Aquaporin-4 Immuneglobulin G testing in 36 consecutive Jamaican patients with inflammatory central nervous system demyelinating disease

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    Sherri Sandy

    2014-08-01

    Full Text Available Epidemiological studies of neuromyelitis optica (NMO in Jamaica are lacking. Here we reviewed the clinical records of 700 patients undergoing neurological evaluation at the Kingston Public Hospital, the largest tertiary institution in Jamaica over a 4 month period. We investigated the diagnostic utility of Aquaporin-4 ImmuneglobulinG (AQP4-IgG testing in 36 consecutive patients with a diagnosis of an inflammatory demyelinating disorder (IDD of the central nervous system (CNS. Patients were classified into 3 categories: i NMO, n=10; ii multiple sclerosis (MS, n=14 and iii unclassified IDD (n=12. All sera were tested for AQP-IgG status by cell binding assay (Euroimmun. No MS cases were positive. Ninety per cent of NMO cases were positive. Four of 12 patients with unclassified IDD tested positive for AQP4-IgG. AQP4-IgG seropositivity was associated with a lower socioeconomic status, higher EDSS (P=0.04 and lower pulmonary function than the seronegative cases (P=0.007. Aquaporin-4 autoimmunity may account for a significant proportion of Jamaican CNS IDDs.

  3. Chronic periodontitis, inflammatory cytokines, and interrelationship with other chronic diseases.

    Science.gov (United States)

    Cardoso, Elsa Maria; Reis, Cátia; Manzanares-Céspedes, Maria Cristina

    2018-01-01

    Periodontal diseases, such as chronic periodontitis, share common inflammatory risk factors with other systemic and chronic inflammatory disorders. Mucosal tissues, such as oral epithelia, are exposed to environmental stressors, such as tobacco and oral bacteria, that might be involved in promoting a systemic inflammatory state. Conversely, chronic disorders can also affect oral health. This review will summarize recent evidence for the interrelationship between chronic periodontitis and other prevalent chronic diseases such as cardiovascular diseases, diabetes, cancer and chronic respiratory diseases. The association with pregnancy is also included due to possible obstetric complications. We will focus on inflammatory cytokines such as TNF-alpha, IL-1, and IL-6, because they have been shown to be increased in patients with chronic periodontitis, in patients with chronic systemic diseases, and in patients with both chronic periodontitis and other chronic diseases. Therefore, an imbalance towards a proinflammatory immune response could underline a bidirectional link between chronic periodontitis and other chronic diseases. Finally, we highlight that a close coordination between dental and other health professionals could promote oral health and prevent or ameliorate other chronic diseases.

  4. Chronic Inflammatory Diseases and Atherosclerotic Cardiovascular Disease

    DEFF Research Database (Denmark)

    Hansen, Peter Riis

    2018-01-01

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

  5. Human Gut-Derived Commensal Bacteria Suppress CNS Inflammatory and Demyelinating Disease.

    Science.gov (United States)

    Mangalam, Ashutosh; Shahi, Shailesh K; Luckey, David; Karau, Melissa; Marietta, Eric; Luo, Ningling; Choung, Rok Seon; Ju, Josephine; Sompallae, Ramakrishna; Gibson-Corley, Katherine; Patel, Robin; Rodriguez, Moses; David, Chella; Taneja, Veena; Murray, Joseph

    2017-08-08

    The human gut is colonized by a large number of microorganisms (∼10 13 bacteria) that support various physiologic functions. A perturbation in the healthy gut microbiome might lead to the development of inflammatory diseases, such as multiple sclerosis (MS). Therefore, gut commensals might provide promising therapeutic options for treating MS and other diseases. We report the identification of human gut-derived commensal bacteria, Prevotella histicola, which can suppress experimental autoimmune encephalomyelitis (EAE) in a human leukocyte antigen (HLA) class II transgenic mouse model. P. histicola suppresses disease through the modulation of systemic immune responses. P. histicola challenge led to a decrease in pro-inflammatory Th1 and Th17 cells and an increase in the frequencies of CD4 + FoxP3 + regulatory T cells, tolerogenic dendritic cells, and suppressive macrophages. Our study provides evidence that the administration of gut commensals may regulate a systemic immune response and may, therefore, have a possible role in treatment strategies for MS. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  6. Transcriptional changes in canine distemper virus-induced demyelinating leukoencephalitis favor a biphasic mode of demyelination.

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    Reiner Ulrich

    Full Text Available Canine distemper virus (CDV-induced demyelinating leukoencephalitis in dogs (Canis familiaris is suggested to represent a naturally occurring translational model for subacute sclerosing panencephalitis and multiple sclerosis in humans. The aim of this study was a hypothesis-free microarray analysis of the transcriptional changes within cerebellar specimens of five cases of acute, six cases of subacute demyelinating, and three cases of chronic demyelinating and inflammatory CDV leukoencephalitis as compared to twelve non-infected control dogs. Frozen cerebellar specimens were used for analysis of histopathological changes including demyelination, transcriptional changes employing microarrays, and presence of CDV nucleoprotein RNA and protein using microarrays, RT-qPCR and immunohistochemistry. Microarray analysis revealed 780 differentially expressed probe sets. The dominating change was an up-regulation of genes related to the innate and the humoral immune response, and less distinct the cytotoxic T-cell-mediated immune response in all subtypes of CDV leukoencephalitis as compared to controls. Multiple myelin genes including myelin basic protein and proteolipid protein displayed a selective down-regulation in subacute CDV leukoencephalitis, suggestive of an oligodendrocyte dystrophy. In contrast, a marked up-regulation of multiple immunoglobulin-like expressed sequence tags and the delta polypeptide of the CD3 antigen was observed in chronic CDV leukoencephalitis, in agreement with the hypothesis of an immune-mediated demyelination in the late inflammatory phase of the disease. Analysis of pathways intimately linked to demyelination as determined by morphometry employing correlation-based Gene Set Enrichment Analysis highlighted the pathomechanistic importance of up-regulated genes comprised by the gene ontology terms "viral replication" and "humoral immune response" as well as down-regulated genes functionally related to "metabolite and energy

  7. Transcriptional changes in canine distemper virus-induced demyelinating leukoencephalitis favor a biphasic mode of demyelination.

    Science.gov (United States)

    Ulrich, Reiner; Puff, Christina; Wewetzer, Konstantin; Kalkuhl, Arno; Deschl, Ulrich; Baumgärtner, Wolfgang

    2014-01-01

    Canine distemper virus (CDV)-induced demyelinating leukoencephalitis in dogs (Canis familiaris) is suggested to represent a naturally occurring translational model for subacute sclerosing panencephalitis and multiple sclerosis in humans. The aim of this study was a hypothesis-free microarray analysis of the transcriptional changes within cerebellar specimens of five cases of acute, six cases of subacute demyelinating, and three cases of chronic demyelinating and inflammatory CDV leukoencephalitis as compared to twelve non-infected control dogs. Frozen cerebellar specimens were used for analysis of histopathological changes including demyelination, transcriptional changes employing microarrays, and presence of CDV nucleoprotein RNA and protein using microarrays, RT-qPCR and immunohistochemistry. Microarray analysis revealed 780 differentially expressed probe sets. The dominating change was an up-regulation of genes related to the innate and the humoral immune response, and less distinct the cytotoxic T-cell-mediated immune response in all subtypes of CDV leukoencephalitis as compared to controls. Multiple myelin genes including myelin basic protein and proteolipid protein displayed a selective down-regulation in subacute CDV leukoencephalitis, suggestive of an oligodendrocyte dystrophy. In contrast, a marked up-regulation of multiple immunoglobulin-like expressed sequence tags and the delta polypeptide of the CD3 antigen was observed in chronic CDV leukoencephalitis, in agreement with the hypothesis of an immune-mediated demyelination in the late inflammatory phase of the disease. Analysis of pathways intimately linked to demyelination as determined by morphometry employing correlation-based Gene Set Enrichment Analysis highlighted the pathomechanistic importance of up-regulated genes comprised by the gene ontology terms "viral replication" and "humoral immune response" as well as down-regulated genes functionally related to "metabolite and energy generation".

  8. Transcriptional Changes in Canine Distemper Virus-Induced Demyelinating Leukoencephalitis Favor a Biphasic Mode of Demyelination

    Science.gov (United States)

    Ulrich, Reiner; Puff, Christina; Wewetzer, Konstantin; Kalkuhl, Arno; Deschl, Ulrich; Baumgärtner, Wolfgang

    2014-01-01

    Canine distemper virus (CDV)-induced demyelinating leukoencephalitis in dogs (Canis familiaris) is suggested to represent a naturally occurring translational model for subacute sclerosing panencephalitis and multiple sclerosis in humans. The aim of this study was a hypothesis-free microarray analysis of the transcriptional changes within cerebellar specimens of five cases of acute, six cases of subacute demyelinating, and three cases of chronic demyelinating and inflammatory CDV leukoencephalitis as compared to twelve non-infected control dogs. Frozen cerebellar specimens were used for analysis of histopathological changes including demyelination, transcriptional changes employing microarrays, and presence of CDV nucleoprotein RNA and protein using microarrays, RT-qPCR and immunohistochemistry. Microarray analysis revealed 780 differentially expressed probe sets. The dominating change was an up-regulation of genes related to the innate and the humoral immune response, and less distinct the cytotoxic T-cell-mediated immune response in all subtypes of CDV leukoencephalitis as compared to controls. Multiple myelin genes including myelin basic protein and proteolipid protein displayed a selective down-regulation in subacute CDV leukoencephalitis, suggestive of an oligodendrocyte dystrophy. In contrast, a marked up-regulation of multiple immunoglobulin-like expressed sequence tags and the delta polypeptide of the CD3 antigen was observed in chronic CDV leukoencephalitis, in agreement with the hypothesis of an immune-mediated demyelination in the late inflammatory phase of the disease. Analysis of pathways intimately linked to demyelination as determined by morphometry employing correlation-based Gene Set Enrichment Analysis highlighted the pathomechanistic importance of up-regulated genes comprised by the gene ontology terms “viral replication” and “humoral immune response” as well as down-regulated genes functionally related to “metabolite and energy

  9. [Correlation between dental pulp demyelination degree and pain visual analogue scale scores data under acute and chronic pulpitis].

    Science.gov (United States)

    Korsantiia, N B; Davarashvili, X T; Gogiashvili, L E; Mamaladze, M T; Tsagareli, Z G; Melikadze, E B

    2013-05-01

    The aim of study is the analysis of pulp nerve fibers demyelination degree and its relationship with Visual Analogue Scale (VAS) score that may be measured as objective criteria. Material and methods of study. Step I: electron micrografs of dental pulp simples with special interest of myelin structural changes detected in 3 scores system, obtained from 80 patients, displays in 4 groups: 1) acute and 2) chronic pulpitis without and with accompined systemic deseases, 20 patients in each group. Dental care was realized in Kutaisi N1 Dental clinic. Step II - self-reported VAS used for describing dental pain. All data were performed by SPSS 10,0 version statistics including Spearmen-rank and Mann-Whitny coefficients for examine the validity between pulp demyelination degree and pain intensity in verbal, numbered and box scales. Researched Data were shown that damaged myelin as focal decomposition of membranes and Schwann cells hyperthrophia correspond with acute dental pain intensity as Spearman index reported in VAS numbered Scales, myelin and axoplasm degeneration as part of chronic gangrenous pulpitis disorders are in direct correlation with VAS in verbal, numbered and behavioral Rating Scales. In fact, all morphological and subjective data, including psychomotoric assessment of dental painin pulpitis may be used in dental practice for evaluation of pain syndrome considered personal story.

  10. Quantifying Demyelination in NK venom treated nerve using its electric circuit model.

    Science.gov (United States)

    Das, H K; Das, D; Doley, R; Sahu, P P

    2016-03-02

    Reduction of myelin in peripheral nerve causes critical demyelinating diseases such as chronic inflammatory demyelinating polyneuropathy, Guillain-Barre syndrome, etc. Clinical monitoring of these diseases requires rapid and non-invasive quantification of demyelination. Here we have developed formulation of nerve conduction velocity (NCV) in terms of demyelination considering electric circuit model of a nerve having bundle of axons for its quantification from NCV measurements. This approach has been validated and demonstrated with toad nerve model treated with crude Naja kaouthia (NK) venom and also shows the effect of Phospholipase A2 and three finger neurotoxin from NK-venom on peripheral nerve. This opens future scope for non-invasive clinical measurement of demyelination.

  11. Quantifying Demyelination in NK venom treated nerve using its electric circuit model

    Science.gov (United States)

    Das, H. K.; Das, D.; Doley, R.; Sahu, P. P.

    2016-03-01

    Reduction of myelin in peripheral nerve causes critical demyelinating diseases such as chronic inflammatory demyelinating polyneuropathy, Guillain-Barre syndrome, etc. Clinical monitoring of these diseases requires rapid and non-invasive quantification of demyelination. Here we have developed formulation of nerve conduction velocity (NCV) in terms of demyelination considering electric circuit model of a nerve having bundle of axons for its quantification from NCV measurements. This approach has been validated and demonstrated with toad nerve model treated with crude Naja kaouthia (NK) venom and also shows the effect of Phospholipase A2 and three finger neurotoxin from NK-venom on peripheral nerve. This opens future scope for non-invasive clinical measurement of demyelination.

  12. Current concepts in chronic inflammatory diseases

    DEFF Research Database (Denmark)

    Garn, Holger; Bahn, Sabine; Baune, Bernhard T

    2016-01-01

    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...

  13. Chronic Inflammatory Gingival Overgrowths: Laser Gingivectomy & Gingivoplasty

    OpenAIRE

    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 LA...

  14. MRI for chronic inflammatory bowel disease

    International Nuclear Information System (INIS)

    Hansmann, H.J.; Hess, T.; Hahmann, M.; Erb, G.; Richter, G.M.; Duex, M.; Elsing, C.

    2001-01-01

    Chronic inflammatory bowel disease is diagnosed and monitored by the combination of colonoscopy and small bowel enteroklysis. Magnetic resonance imaging has become the gold standard for the imaging of perirectal and pelvic fistulas. With the advent of ultrafast MRI small and large bowel imaging has become highly attractive and is being advocated more and more in the diagnostic work up of inflammatory bowel disease. Imaging protocols include fast T 1 -weighted gradient echo and T 2 -weighted TSE sequences and oral or rectal bowel distension. Furthermore, dedicated imaging protocols are based on breath-hold imaging under pharmacological bowel paralysis and gastrointestinal MR contrast agents (Hydro-MRI). High diagnostic accuracy can be achieved in Crohn's disease with special reference to the pattern of disease, depth of inflammation, mesenteric reaction, sinus tract depiction and formation of abscess. In ulcerative colitis, the mucosa-related inflammation causes significantly less bowel wall thickening compared to Crohn's disease. Therefore with MRI, the extent of inflammatory changes is always underestimated compared to colonoscopy. According to our experience in more than 200 patients as well as the results in other centers, Hydro-MRI possesses the potential to replace enteroklysis in the diagnosis of chronic inflammatory bowel disease and most of the follow-up colonoscopies in Crohn's disease. Further technical improvements in 3D imaging will allow interactive postprocessing of the MR data. (orig.) [de

  15. Experimental mouse model of optic neuritis with inflammatory demyelination produced by passive transfer of neuromyelitis optica-immunoglobulin G

    Science.gov (United States)

    2014-01-01

    Background Although optic neuritis (ON) is a defining feature of neuromyelitis optica (NMO), appropriate animal models of NMO ON are lacking. Most NMO patients are seropositive for immunoglobulin G autoantibodies (NMO-IgG) against the astrocyte water channel aquaporin-4 (AQP4). Methods Several approaches were tested to develop a robust, passive-transfer mouse model of NMO ON, including NMO-IgG and complement delivery by: (i) retrobulbar infusion; (ii) intravitreal injection; (iii) a single intracranial injection near the optic chiasm; and (iv) 3-days continuous intracranial infusion near the optic chiasm. Results Little ON or retinal pathology was seen using approaches (i) to (iii). Using approach (iv), however, optic nerves showed characteristic NMO pathology, with loss of AQP4 and glial fibrillary acidic protein immunoreactivity, granulocyte and macrophage infiltration, deposition of activated complement, demyelination and axonal injury. Even more extensive pathology was created in mice lacking complement inhibitor protein CD59, or using a genetically modified NMO-IgG with enhanced complement effector function, including significant loss of retinal ganglion cells. In control studies, optic nerve pathology was absent in treated AQP4-deficient mice, or in wild-type mice receiving control (non-NMO) IgG and complement. Conclusion Passive transfer of NMO-IgG and complement by continuous infusion near the optic chiasm in mice is sufficient to produce ON with characteristic NMO pathology. The mouse model of NMO ON should be useful in further studies of NMO pathogenesis mechanisms and therapeutics. PMID:24468108

  16. [Local demyelination in amyotrophic lateral sclerosis].

    Science.gov (United States)

    Kvirkvelia, N; Shakarishvili, R

    2013-02-01

    It is well known that the demyelination of peripheral nerves can be diffuse or local. Pathogenesis of acute or chronic inflamentary demyelination polyneurophathy is based on diffuse demyelination. Local demyelination occured by conduction block with electoneuromyographic (ENMG) researches. It is the main characteristic of multifocal motor neuropathy (MMN). Generally it is considered, that conduction block is not usual for amyotrophic lateral sclerosis (ALS). More over, its existance excludes this diagnosis. The article discribes 3 cases of ALS with conduction block verified with ENMG researches. Article also deals with pathogenetic mechanisms of conduction block in ALS and MMN. In addition it observes the issues of differential diagnosis between ALS and MMW.

  17. Resistance training and aerobic training improve muscle strength and aerobic capacity in chronic inflammatory demyelinating polyneuropathy

    DEFF Research Database (Denmark)

    Markvardsen, Lars H; Overgaard, Kristian; Heje, Karen

    2018-01-01

    after a run-in period of 12 weeks without exercise. Three times weekly the participants performed aerobic exercise on an ergometer bike or resistance exercise with unilateral training of knee and elbow flexion/extension. Primary outcomes were maximal oxygen consumption velocity (VO2 -max) and maximal...

  18. Cerebrospinal fluid findings in Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathies

    DEFF Research Database (Denmark)

    Illes, Zsolt; Blaabjerg, Morten

    2017-01-01

    The classic immunologic alteration of the cerebrospinal fluid (CSF) in Guillain-Barré syndrome (GBS), albuminocytologic dissociation, has been known since the original paper by Guillain, Barré, and Strohl. Albuminocytologic dissociation has been also described in other forms of the GBS spectrum...

  19. Atypical idiopathic inflammatory demyelinating lesions (IIDL): Conventional and diffusion-weighted MR imaging (DWI) findings in 42 cases

    Energy Technology Data Exchange (ETDEWEB)

    Koelblinger, Claus; Fruehwald-Pallamar, Julia [Department of Biomedical Imaging and Image-Guided Therapy, Medical University Vienna, Vienna (Austria); Kubin, Klaus [CT/MRI Institut Dr. Klaus Kubin, Salzburg (Austria); Wallner-Blazek, Mirja [Department of Neurology, Medical University Graz, Graz (Austria); Hauwe, Luc van den [Department of Radiology, Medical University of Antwerp, Antwerp (Belgium); Macedo, Leonardo [Department of Radiology, CEDIMAGEM, Centro - Juiz de Fora (Brazil); Puchner, Stefan B. [Department of Biomedical Imaging and Image-Guided Therapy, Medical University Vienna, Vienna (Austria); Thurnher, Majda M., E-mail: majda.thurnher@meduniwien.ac.at [Department of Biomedical Imaging and Image-Guided Therapy, Medical University Vienna, Vienna (Austria)

    2013-11-01

    Introduction: The purpose of this study was to evaluate MR imaging characteristics with conventional and advanced MR imaging techniques in patients with IIDL. Methods: MR images of the brain in 42 patients (20 male, 22 female) with suspected or known multiple sclerosis (MS) from four institutions were retrospectively analyzed. Lesions were classified into five different subtypes: (1) ring-like lesions; (2) Balo-like lesions; (3) diffuse infiltrating lesions; (4) megacystic lesions; and (5) unclassified lesions. The location, size, margins, and signal intensities on T1WI, T2WI, and diffusion-weighted images (DWI), and the ADC values/ratios for all lesions, as well as the contrast enhancement pattern, and the presence of edema, were recorded. Results: There were 30 ring-like, 10 Balo-like, 3 megacystic-like and 16 diffuse infiltrating-like lesions were detected. Three lesions were categorized as unclassified lesions. Of the 30 ring-like lesions, 23 were hypointense centrally with a hyperintense rim. The mean ADC, measured centrally, was 1.50 ± 0.41 × 10{sup −3} mm{sup 2}/s. The mean ADC in the non-enhancing layers of the Balo-like lesions was 2.29 ± 0.17 × 10{sup −3} mm{sup 2}/s, and the mean ADC in enhancing layers was 1.03 ± 0.30 × 10{sup −3} mm{sup 2}/s. Megacystic lesions had a mean ADC of 2.14 ± 0.26 × 10{sup −3} mm{sup 2}/s. Peripheral strong enhancement with high signal on DWI was present in all diffuse infiltrating lesions. Unclassified lesions showed a mean ADC of 1.43 ± 0.13 mm{sup 2}/s. Conclusion: Restriction of diffusion will be seen in the outer layers of active inflammation/demyelination in Balo-like lesions, in the enhancing part of ring-like lesions, and at the periphery of infiltrative-type lesions.

  20. Central Nervous System Demyelination and Remyelination is Independent from Systemic Cholesterol Level in Theiler's Murine Encephalomyelitis.

    Science.gov (United States)

    Raddatz, Barbara B; Sun, Wenhui; Brogden, Graham; Sun, Yanyong; Kammeyer, Patricia; Kalkuhl, Arno; Colbatzky, Florian; Deschl, Ulrich; Naim, Hassan Y; Baumgärtner, Wolfgang; Ulrich, Reiner

    2016-01-01

    High dietary fat and/or cholesterol intake is a risk factor for multiple diseases and has been debated for multiple sclerosis. However, cholesterol biosynthesis is a key pathway during myelination and disturbances are described in demyelinating diseases. To address the possible interaction of dyslipidemia and demyelination, cholesterol biosynthesis gene expression, composition of the body's major lipid repositories and Paigen diet-induced, systemic hypercholesterolemia were examined in Theiler's murine encephalomyelitis (TME) using histology, immunohistochemistry, serum clinical chemistry, microarrays and high-performance thin layer chromatography. TME-virus (TMEV)-infected mice showed progressive loss of motor performance and demyelinating leukomyelitis. Gene expression associated with cholesterol biosynthesis was overall down-regulated in the spinal cord of TMEV-infected animals. Spinal cord levels of galactocerebroside and sphingomyelin were reduced on day 196 post TMEV infection. Paigen diet induced serum hypercholesterolemia and hepatic lipidosis. However, high dietary fat and cholesterol intake led to no significant differences in clinical course, inflammatory response, astrocytosis, and the amount of demyelination and remyelination in the spinal cord of TMEV-infected animals. The results suggest that down-regulation of cholesterol biosynthesis is a transcriptional marker for demyelination, quantitative loss of myelin-specific lipids, but not cholesterol occurs late in chronic demyelination, and serum hypercholesterolemia exhibited no significant effect on TMEV infection. © 2015 International Society of Neuropathology.

  1. Chronic inflammatory and suppurative processes in lungs

    International Nuclear Information System (INIS)

    Rozenshtraukh, L.C.; Rybakova, N.I.; Vinner, M.G.

    1987-01-01

    Roentgenologic methods of diagnosis of chronic bronchitis, bronchiectatic disease, lung abscess and gangrene, chronic non-specific pneumonia and cancer of lung and other pathalogical changes at chronic processes in lungs are discussed in detail

  2. Biologic therapies for chronic inflammatory bowel disease

    Directory of Open Access Journals (Sweden)

    M. P. Martínez-Montiel

    Full Text Available Crohn's disease (CD and ulcerative colitis (UC make up the so-called chronic inflammatory bowel disease (IBD. Advances in the understanding of IBD pathophysiologic mechanisms in the last few years have allowed the development of novel therapies such as biologic therapies, which at least theoretically represent a more specific management of this disease with fewer side effects. Currently, the only effective and widely accepted biologic therapy for the treatment of intraluminal, fistulizing CD, both for remission induction and maintenance, is infliximab. The role of other monoclonal antibodies such as adalimumab is not clearly established. It could be deemed an alternative for patients with allergic reactions to infliximab, and for those with lost response because of anti-infliximab antibody development. However, relevant issues such as dosage and administration regimen remain to be established. Anti-integrin α4 therapies, despite encouraging results in phase-3 studies, are still unavailable, as their marketing authorization was held back in view of a number of reports regarding progressive multifocal leukoencephalopathy cases. Immunostimulating therapy may be highly relevant in the near future, as it represents a novel strategy against disease with the inclusion of granulocyte-monocyte colony-stimulating factors. Regarding ulcerative colitis, results from the ACT-1 and ACT-2 studies showed that infliximab is also useful for the management of serious UC flare-ups not responding to standard treatment, which will lead to a revision of therapeutic algorithms, where this drug should be given preference before intravenous cyclosporine. In the next few years, the role of anti-CD3 drugs (vilisilizumab, T-cell inhibiting therapies, and epithelial repair and healing stimulating factors will be established.

  3. Chronic Inflammatory Disease, Lifestyle and Treatment Response

    Science.gov (United States)

    2018-01-25

    Autoimmune Diseases; Inflammatory Bowel Diseases; Crohn Disease (CD); Colitis, Ulcerative (UC); Arthritis, Rheumatoid (RA); Spondylarthropathies; Arthritis, Psoriatic (PsA); Psoriasis; Hidradenitis Suppurativa (HS); Uveitis

  4. Actualización en el tratamiento de la neuropatía óptica inflamatoria desmielinizante Updating on the treatment of the demyelinating inflammatory optical neuropathy

    Directory of Open Access Journals (Sweden)

    Yaimara Hernández Silva

    2011-06-01

    Full Text Available Se realizó una revisión bibliográfica con el objetivo de proporcionar una actualización de las drogas que se emplean para retrasar la aparición de esclerosis múltiple en el manejo de la neuropatía óptica inflamatoria desmielinizante. El artículo presenta el origen y la justificación de la terapia esteroidea en este grupo de enfermedad, así como los mecanismos de acción y beneficios de tratamientos más modernos como los inmunomoduladores e inmunosupresores. El trabajo también introduce muchas de las drogas con efectos neuroprotectores que se encuentran en fases experimentales, cuyo uso prevendría la neurodegeneración que se produce a nivel de las células ganglionares retinianas en esta enfermedad neurológica. Las opciones terapéuticas actuales ofrecen variantes de tratamiento adicionales a pacientes con mayores probabilidades de desarrollo de esclerosis múltiple y retrasan la aparición de un segundo brote, así como las secuelas invalidantes que esta suele originar.A bibliographic review was conducted to provide an updating of drugs used to retard the appearance of multiple sclerosis in the management of the demyelinating inflammatory optical neuropathy. Present paper shows the origin and the justification of the steroid therapy in this disease, as well as the mechanisms of action and benefits of more recent treatments, e.g. the ongoing immunomodulations and immunosuppressive ones and also to introduce many drugs in experimental phase having neuroprotection effects whose use will prevent the neurodegenerative effect produced at level of the retinal ganglion cells in this neurologic disease. The current therapeutical options offer variants of additional treatment to those patients with greater possibilities to development multiple sclerosis and retarding the appearance of a second outbreak, as well as its disabling sequelae.

  5. Chronic Inflammatory Periodontal Disease in Patients with Human Immunodeficiency Virus.

    OpenAIRE

    Vania López Rodríguez; Emilio Carpio Muñoz; Vicente Fardales Macías; Iralys Benítez Guzmán

    2009-01-01

    Background: The Chronic Inflammatory Periodontal Disease is related with multiple risk factors. Those patients with human immunodeficiency virus have higher risk of presenting this disease and it is usually more serious in these cases. Objective: To describe the prevalence of Chronic Inflammatory Periodontal Disease in patients with HIV. Methods: Descriptive, observational, cross-sectional study including patients with HIV in Sancti Spiritus province. The occurrence of the disease was determi...

  6. Diagnosis and treatment of chronic inflammatory diseases of parodontium

    International Nuclear Information System (INIS)

    Khitrov, V.Yu.; Zabolotnyj, A.I.; Khamidullina, S.A.

    1995-01-01

    Chronic inflammatory diseases of paradontium have the higher share in the structure of paradontal tissue injuries. The state of bone paradontium is monitored using roentgenographic techniques. The clinical picture of chronic inflammatory diseases consists of the signs of injury of different components of parodontium: gum, periodontitis and alveo bone. The treatment of patients in aimed at eliminating the symptoms of the disease recovery of masticatory ability and prevention of recurrences

  7. Inflammatory Cell Infiltrates in Acute and Chronic Thoracic Aortic Dissection.

    Science.gov (United States)

    Wu, Darrell; Choi, Justin C; Sameri, Aryan; Minard, Charles G; Coselli, Joseph S; Shen, Ying H; LeMaire, Scott A

    2013-12-01

    Thoracic aortic dissection (TAD) is a highly lethal cardiovascular disease. Injury to the intima and media allows pulsatile blood to enter the media, leading to dissection formation. Inflammatory cells then infiltrate the site of aortic injury to clear dead cells and damaged tissue. This excessive inflammation may play a role in aneurysm formation after dissection. Using immunohistochemistry, we compared aortic tissues from patients with acute TAD (n = 11), patients with chronic TAD (n = 35), and donor controls (n = 20) for the presence of CD68+ macrophages, neutrophils, mast cells, and CD3+ T lymphocytes. Tissue samples from patients with acute or chronic TAD generally had significantly more inflammatory cells in both the medial and adventitial layers than did the control samples. In tissues from patients with acute TAD, the adventitia had more of the inflammatory cells studied than did the media. The pattern of increase in inflammatory cells was similar in chronic and acute TAD tissues, except for macrophages, which were seen more frequently in the adventitial layer of acute TAD tissue than in the adventitia of chronic TAD tissue. The inflammatory cell content of both acute and chronic TAD tissue was significantly different from that of control tissue. However, the inflammatory cell profile of aneurysmal chronic TAD was similar to that of acute TAD. This may reflect a sustained injury response that contributes to medial degeneration and aneurysm formation.

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

    Science.gov (United States)

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

    2015-06-04

    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. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  9. The Prevalence of Anti-Aquaporin 4 Antibody in Patients with Idiopathic Inflammatory Demyelinating Diseases Presented to a Tertiary Hospital in Malaysia: Presentation and Prognosis

    Directory of Open Access Journals (Sweden)

    S. Abdullah

    2017-01-01

    Full Text Available Background. There have been inconsistent reports on the prevalence and pathogenicity of anti-Aquaporin 4 (AQP4 in patients presented with idiopathic inflammatory demyelinating diseases (IIDDs. Objective. To estimate the prevalence of anti-AQP4 antibody in patients with IIDDs presented to University Malaya Medical Centre in terms of patients’ clinical and radiological presentations and prognoses. Methods. Retrospective data review of IIDDs patients presented from 2005 to 2015. Patients were classified into classical multiple sclerosis (CMS, opticospinal (OS presentation, optic neuritis (ON, transverse myelitis (TM, brainstem syndrome (BS, and tumefactive MS. Anti-Aquaporin 4 antibody was tested using the Indirect Immunofluorescence Test (IIFT cell-based assay. Statistical analysis was done using the SPSS version 20. Results. Anti-AQP4 antibody was detected in 53% of patients presented with IIDDs. CMS was more common in the seronegative group, 27/47 (57.45%; p<0.001. Conversely, OS involvement was more common in the seropositive group, 26/53 (49.06%; p<0.001. Longitudinally extensive spinal cord lesions (LESCLs on MRI were also more common in the seropositive group, 29/40 (72.50%; p=0.004. Only 2/40 (5.00% had MRI evidence of patchy or multiple short-segment spinal cord lesions in the AQP4-positive group (p=0.003. The relapse rate and Expanded Disability Status Scale (EDSS were also higher in the seropositive group (5.43 versus 3.17, p=0.005; 4.07 versus 2.51, p=0.006, resp.. Typical clinical presentations that defined NMO were also seen in the seronegative patients, but in a lower frequency. Conclusion. Our cohort of patients had a higher prevalence of seropositivity of anti-AQP4 antibody as compared to those in Western countries. This was also associated with a more typical presentation of opticospinal involvement with LESCLs on MRI, a higher rate of relapse, and EDSS.

  10. Macrolides in Chronic Inflammatory Skin Disorders

    Directory of Open Access Journals (Sweden)

    Abdullateef A. Alzolibani

    2012-01-01

    Full Text Available Long-term therapy with the macrolide antibiotic erythromycin was shown to alter the clinical course of diffuse panbronchiolitis in the late 1980s. Since that time, macrolides have been found to have a large number of anti-inflammatory properties in addition to being antimicrobials. These observations provided the rationale for many studies performed to assess the usefulness of macrolides in other inflammatory diseases including skin and hair disorders, such as rosacea, psoriasis, pityriasis rosea, alopecia areata, bullous pemphigoid, and pityriasis lichenoides. This paper summarizes a collection of clinical studies and case reports dealing with the potential benefits of macrolides antibiotics in the treatment of selected dermatoses which have primarily been classified as noninfectious and demonstrating their potential for being disease-modifying agents.

  11. Macrolides in Chronic Inflammatory Skin Disorders

    Science.gov (United States)

    Alzolibani, Abdullateef A.; Zedan, Khaled

    2012-01-01

    Long-term therapy with the macrolide antibiotic erythromycin was shown to alter the clinical course of diffuse panbronchiolitis in the late 1980s. Since that time, macrolides have been found to have a large number of anti-inflammatory properties in addition to being antimicrobials. These observations provided the rationale for many studies performed to assess the usefulness of macrolides in other inflammatory diseases including skin and hair disorders, such as rosacea, psoriasis, pityriasis rosea, alopecia areata, bullous pemphigoid, and pityriasis lichenoides. This paper summarizes a collection of clinical studies and case reports dealing with the potential benefits of macrolides antibiotics in the treatment of selected dermatoses which have primarily been classified as noninfectious and demonstrating their potential for being disease-modifying agents. PMID:22685371

  12. Prevalence of chronic diseases at the onset of inflammatory arthritis.

    NARCIS (Netherlands)

    Ursum, J.; Korevaar, J.C.; Twisk, J.W.R.; Peters, M.J.L.; Schellevis, F.G.; Nurmohamed, M.T.; Nielen, M.M.J.

    2012-01-01

    Background: To explore the prevalence of chronic diseases at the onset of inflammatory arthritis (IA) in the general practice and compare this to a group of control patients without IA. Methods: In this nested-case-control study, data were used from the Netherlands Information Network of eneral

  13. Innate lymphoid cells in autoimmunity and chronic inflammatory diseases.

    Science.gov (United States)

    Xiong, Tingting; Turner, Jan-Eric

    2018-03-22

    Abnormal activation of the innate immune system is a common feature of autoimmune and chronic inflammatory diseases. Since their identification as a separate family of leukocytes, innate lymphoid cells (ILCs) have emerged as important effector cells of the innate immune system. Alterations in ILC function and subtype distribution have been observed in a variety of immune-mediated diseases in humans and evidence from experimental models suggests a subtype specific role of ILCs in the pathophysiology of autoimmune inflammation. In this review, we discuss recent advances in the understanding of ILC biology in autoimmune and chronic inflammatory disorders, including multiple sclerosis, inflammatory bowel diseases, psoriasis, and rheumatic diseases, with a special focus on the potential of ILCs as therapeutic targets for the development of novel treatment strategies in humans.

  14. Demyelinating diseases in Asia.

    Science.gov (United States)

    Ochi, Hirofumi; Fujihara, Kazuo

    2016-06-01

    The present review aims to discuss the recent advances in inflammatory demyelinating diseases of the central nervous system in Asia. Prevalence of multiple sclerosis (MS) in Asia is lower than that in Western countries, although it has been increasing recently. Meanwhile, there seems to be no major difference in neuromyelitis optica (NMO) prevalence in various regions or ethnicities. Thus, the ratios of NMO/NMO spectrum disorder (NMOSD) to MS are higher in Asia as compared with Western countries, indicating that the differential diagnosis between NMO/NMOSD and MS is a major challenge in Asia. Although the detection of aquaporin-4 (AQP4)-antibody is critical in distinguishing NMO/NMOSD from MS, some patients with NMO/NMOSD phenotype are seronegative for AQP4-antibody, and a fraction of those patients possess autoantibody against myelin oligodendrocyte glycoprotein. The clinical profile of Asian MS seems to be essentially similar to that in Western MS after careful exclusion of NMO/NMOSD, although some unique genetic and/or environmental factors may modify the disease in Asians. MS prevalence has been low but is increasing in Asia. In contrast, NMO/NMOSD prevalence seems relatively constant in the world. Asian MS is not fundamentally different from Western MS, but some genetic and/or environmental differences may cause some features unique to Asian patients.

  15. Management of Cardiovascular Risk in Patients with Chronic Inflammatory Diseases

    DEFF Research Database (Denmark)

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

    2016-01-01

    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...... 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...

  16. Hypothalamic demyelination causing panhypopituitarism.

    Science.gov (United States)

    Dixon-Douglas, Julia; Burgess, John; Dreyer, Michael

    2018-05-01

    Hypothalamic involvement in multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) is rare and endocrinopathies involving the hypothalamic-pituitary axis in patients with demyelinating conditions have rarely been reported. We present two cases of MS/NMOSD with associated hypothalamic-pituitary involvement and subsequent hypopituitarism, including the first report of a patient with hypothalamic demyelination causing panhypopituitarism. Differential diagnoses, including alemtuzumab-related and primary pituitary pathology are discussed. © 2018 Royal Australasian College of Physicians.

  17. A histopathologic analysis of chronic inflammatory infiltrate in patients of h. pylori associated chronic gastritis

    International Nuclear Information System (INIS)

    Khalid, H.; Zubair, A.; Malik, T.M.

    2015-01-01

    To determine the relationship between H. pylori density with severity of chronic inflammatory infiltrate. Study Design: A cross-sectional study. Place and Duration of Study: The study was carried out in the Department of Pathology (Histopathology), Army Medical College, National University of Sciences and Technology (NUST) Islamabad, from Nov 2011 to Nov 2012. Methodology: Gastric antral biopsies of H. pylori associated chronic gastritis were included in the study. Demographic characteristics and relevant clinical information were collected. First hundred biopsies of H. pylori associated chronic gastritis were assessed for density of H. pylori and chronic inflammatory infiltrate. istopathological features like lymphoid aggregates, ulcer slough, superficial epithelial damage, dysplasia and nuclear reactive changes were simply assessed in case of their presence or absence. Results: A significant moderate positive correlation was found between grades of H. pylori and chronic inflammatory infiltrate (rs= 0.636). Insignificant correlation was found with lymphoid aggregates, superficial epithelial damage, dysplasia and nuclear reactive changes. Conclusion: In conclusion this study corroborated the determination of histopathological parameters and depicted that, the greater the density of H. pylori infection, the greater the degrees of chronic inflammatory infiltrate. (author)

  18. Inflammatory chronic disease of the colon: How to image

    International Nuclear Information System (INIS)

    Ambrosini, Roberta; Barchiesi, Annalisa; Di Mizio, Veronica; Di Terlizzi, Marco; Leo, Luca; Filippone, Antonella; Canalis, Luigi; Fossaceca, Rita; Carriero, Alessandro

    2007-01-01

    Inflammatory bowel disease, including Crohn's disease and UC, is a chronic disorder of the gastrointestinal tract. The inflammatory process in UC is confined to the mucosa and submucosa and it involves only the colon. In contrast, in Crohn's disease the inflammation process extends through the bowel wall layers and it can involve any part of gastrointestinal tract. Moreover, inflammatory bowel disease of the colon may be associated with complications, such as toxic megacolon, fulminant colitis, acute bleeding, fistulas and abscesses. Radiographic imaging studies are useful for the diagnosis of inflammatory bowel disease, and may be used to assess the extent and severity of disease, rule out complications, and monitor the response to therapy. The double-contrast barium study is a valuable technique for diagnosing inflammatory bowel disease colonic alterations, even in patients with early mucosal abnormalities. The earliest finding of UC is characterized by a fine granular appeareance of the colonic mucosa, usually involving the rectosigmoid junction. In chronic UC double-contrast enema may reveal marked colonic shortening with tubular narrowing of the bowel and loss of haustration. The earliest radiographics findings of Crohn's disease are represented by aphthous ulcers. As disease progresses, aphthous ulcers may enlarge and coalesce to form stellate or linear areas of ulceration. In advanced Crohn's disease, transmural ulceration may lead to the development of fissures, sinus tracts, fistulas, and abscesses. Cross sectional studies such as computed tomography, magnetic resonance imaging and sometimes ultrasound, are useful alternative tools not only in the assessment of bowel wall abnormalities, but also for the assessment of extraluminal alterations in patients with advanced disease

  19. The effects of acute and chronic exercise on inflammatory markers in children and adults with a chronic inflammatory disease: a systematic review

    NARCIS (Netherlands)

    Ploeger, Hilde E.; Takken, Tim; de Greef, Mathieu H. G.; Timmons, Brian W.

    2009-01-01

    Chronic inflammatory diseases strike millions of people all over the world, and exercise is often prescribed for these patients to improve overall fitness and quality of life. In healthy individuals, acute and chronic exercise is known to alter inflammatory markers; however, less is known about

  20. The effects of acute and chronic exercise on inflammatory markers in children and adults with a chronic inflammatory disease : a systematic review

    NARCIS (Netherlands)

    Ploeger, Hilde E.; Takken, Tim; de Greef, Mathieu H. G.; Timmons, Brian W.

    2009-01-01

    Background: Chronic inflammatory diseases strike millions of people all over the world, and exercise is often prescribed for these patients to improve overall fitness and quality of life. In healthy individuals, acute and chronic exercise is known to alter inflammatory markers; however, less is

  1. An Occult Malignancy Behind a Demyelinating Disease

    Directory of Open Access Journals (Sweden)

    Saberio Lo Presti MD

    2016-10-01

    Full Text Available We report a case of a 38-year-old man presenting with bilateral lower extremity weakness and paresthesias that progressed during a 4-month period to severe polyneuropathy forcing the patient to be bed bound. Throughout his multiple hospitalizations, he was treated erroneously for chronic inflammatory demyelinating polyneuropathy, without significant improvement in his symptoms. In addition, he developed hepatosplenomegaly (organomegaly; endocrinopathies such as diabetes mellitus, central hypogonadism, and hypothyroidism; monoclonal spike evidenced in the serum electrophoresis; and hyperpigmentation of skin, altogether consistent with POEMS syndrome. During his last hospitalization he developed excruciating pain on his left hip, and imaging revealed the presence of a 9 × 6 cm osteolytic mass with sclerotic rim in the left acetabulum. Biopsy of the mass confirmed an isolated IgG lambda plasmacytoma. The patient received radiation to his left acetabular lesion followed by left hip replacement. Subsequently, the patient underwent autologous bone marrow transplant. Eighteen months after his initial presentation, he had satisfactory clinical response and is functional without significant limitations. POEMS syndrome is a rare paraneoplastic syndrome secondary to an underlying plasma cell disorder, which can oftentimes be overlooked and misdiagnosed. The median age of presentation is 51 years, and only 31% of the cases occur in fairly young patients under the age of 45 as evidenced in this case. As clinicians, we should be aware of the constellation of features associated with POEMS syndrome and be able to recognize them promptly.

  2. Solitary osteosclerotic plasmacytoma: association with demyelinating polyneuropathy and amyloid deposition

    Energy Technology Data Exchange (ETDEWEB)

    Voss, S.D.; Hall, F.M. [Dept. of Radiology, Beth Israel Deaconess Medical Center, Boston, MA (United States); Harvard Medical School, Boston, MA (United States); Murphey, M.D. [Dept. of Radiologic Pathology, Armed Forces Institute of Pathology, Washington, DC (United States); Dept. of Radiology and Nuclear Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD (United States); Department of Radiology, University of Maryland School of Medicine, Baltimore, Maryland (United States)

    2001-09-01

    A 51-year-old man presented with a 1-year history of polyneuropathy necessitating the use of a wheelchair. Initial diagnosis was idiopathic chronic inflammatory demyelinating polyneuropathy (CIDP) and associated monoclonal gammopathy. Investigations for multiple myeloma, including bone marrow aspiration and biopsy, were negative. What was initially felt to be an incidental osteosclerotic focus noted on the radiographic bone survey was eventually shown to be a solitary osteosclereotic plasmacytoma with associated amyloid. This dramatically altered treatment. This case emphasizes the importance of including osteosclerotic plasmacytoma in the differential diagnosis of a focal sclerotic bone lesion in the clinical setting of polyneuropathy. These lesions are less likely to progress to multiple myeloma than lytic plasma cell neoplasms, and the presence of polyneuropathy often results in earlier diagnosis and treatment with enhanced prospect of cure. The finding of amyloid deposition within the osteosclerotic lesion may be of prognostic importance. (orig.)

  3. Chronic post-inflammatory fatigue in sarcoidosis : from cytokines to behavior

    NARCIS (Netherlands)

    Korenromp, I.H.E.

    2011-01-01

    Sarcoidosis is a systemic inflammatory disorder that is characterized by granuloma formation in different organs. Sarcoidosis patients frequently report fatigue. Even when the clinical symptoms of the inflammatory disease sarcoidosis have resolved, chronic fatigue may persist. In this study 75

  4. A Proposal for a Study on Treatment Selection and Lifestyle Recommendations in Chronic Inflammatory Diseases

    DEFF Research Database (Denmark)

    Andersen, Vibeke; Holmskov, Uffe; Sørensen, Signe Bek

    2017-01-01

    Chronic inflammatory diseases (CIDs), including Crohn’s disease and ulcerative colitis (inflammatory bowel diseases, IBD), rheumatoid arthritis, psoriasis, psoriatic arthritis, spondyloarthritides, hidradenitis suppurativa, and immune-mediated uveitis, are treated with biologics targeting the pro...

  5. A Proposal for a Study on Treatment Selection and Lifestyle Recommendations in Chronic Inflammatory Diseases

    DEFF Research Database (Denmark)

    Andersen, Vibeke; Holmskov, Uffe; Sørensen, Signe Bek

    2017-01-01

    Chronic inflammatory diseases (CIDs), including Crohn's disease and ulcerative colitis (inflammatory bowel diseases, IBD), rheumatoid arthritis, psoriasis, psoriatic arthritis, spondyloarthritides, hidradenitis suppurativa, and immune-mediated uveitis, are treated with biologics targeting the pro...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2005-12-11

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

  7. Modern MRI tools for the characterization of acute demyelinating lesions: value of chemical shift and diffusion-weighted imaging

    International Nuclear Information System (INIS)

    Kueker, W.; Mehnert, F.; Mader, I.; Naegele, T.; Ruff, J.; Gaertner, S.

    2004-01-01

    Acute demyelinating lesions occur in various inflammatory disorders of the CNS. Apart from multiple sclerosis, most cases can be attributed to an overshooting immunological response to infectious agents called acute disseminated encephalomyelitis (ADEM). ADEM, which is mostly characterized by a monophasic course, has a multiphasic variant (MDEM). The early application of corticosteroids has been shown to be beneficial for the outcome; thus, an early diagnosis is highly desirable. Furthermore, the differential diagnosis ruling out neoplastic disorders may be difficult using conventional MRI alone. The potential diagnostic value of advanced MR techniques such as chemical shift imaging (CSI) and diffusion-weighted imaging (DWI) was investigated in a patient with MDEM, who had a new lesion in continuity with the initial disease manifestation. CSI was performed at 1.5 T with a long echo time of 135 ms for the evaluation of N-acetyl-aspartate (NAA) and choline (Cho) and with short TE of 30 ms for macromolecules (mm) and myo-Inositol (mI). DWI was performed using a single-shot isotropic EPI sequence. Whereas acute and chronic areas of demyelination were neither distinguishable on T2- nor on contrast-enhanced T1-weigted images, CSI and DWI revealed different metabolite concentrations and diffusion characteristics within the composite lesion, clearly separating acute from chronic areas of demyelination. In conclusion, the addition of CSI and DWI may add to the diagnostic power of MRI in the setting of demyelinating disorders by identifying areas of acute and chronic demyelination, even in the absence of contrast enhancement. (orig.)

  8. Restless leg syndrome in different types of demyelinating neuropathies: a single-center pilot study.

    Science.gov (United States)

    Luigetti, Marco; Del Grande, Alessandra; Testani, Elisa; Bisogni, Giulia; Losurdo, Anna; Giannantoni, Nadia Mariagrazia; Mazza, Salvatore; Sabatelli, Mario; Della Marca, Giacomo

    2013-09-15

    to determine the prevalence of restless legs syndrome (RLS) in a cohort of patients with demyelinating neuropathies. Patients were retrospectively recruited from our cohort of different forms of demyelinating neuropathies, including chronic inflammatory demyelinating neuropathy (CIDP), Charcot-Marie-Tooth 1A (CMT1A), and hereditary neuropathy with liability to pressure palsies (HNPP) referred to our Department of Neurology in a 10-year period. The validated 4-item RLS questionnaire was used for diagnosis of RLS. All patients with RLS who fulfilled criteria underwent a suggested immobilization test to confirm the diagnosis. A group of outpatients referred to the sleep disorders unit and data from published literature were used as controls. Prevalence of RLS in demyelinating neuropathy group was higher than prevalence observed in control population (p = 0.0142) or in the literature data (p = 0.0007). In particular, in comparison with both control population and literature data, prevalence of RLS was higher in CIDP group (p = 0.0266 and p = 0.0063, respectively) and in CMT1A group (p = 0.0312 and p = 0.0105, respectively), but not in HNPP (p = 1.000 and p = 0.9320, respectively). our study confirms a high prevalence of RLS in inflammatory neuropathies as CIDP and, among inherited neuropathies, in CMT1A but not in HNPP. Considering that this is only a small cohort from a single-center retrospective experience, the link between RLS and neuropathy remains uncertain, and larger multicenter studies are probably needed to clarify the real meaning of the association between RLS and neuropathy.

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

    Science.gov (United States)

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

    2018-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Luca Parisi

    2018-01-01

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

  11. Study on the chronic inflammatory status in patients with chronic renal failure (CRF)

    International Nuclear Information System (INIS)

    Deng Lirong; Wang Caili; Wei Hong; Yang Yuhua

    2005-01-01

    Objective: To study the relationship between the status of chronic inflammation and deterioration of renal function in patients with chronic renal failure (CRF). Methods: Serum CRP, IL-10 (with ELISA), TNF-α, IL-6 (with RIA) and creatinine (with bio-chemistry methods) levels were determined in 126 patients with CRF of various stages as well as in 30 controls. The creatinine clearance rate (CCr) was also calculated. Results: (1)In all these patients, the serum CRP, IL-6, IL-10 and TNF-α contents were significantly higher than those in the controls (P <0.01). (2) CRP, IL-6, IL-10 and TNF-α levels were linearly positively correlated with the creatinine levels (r= 0.716, 0.836, 0.501 and 0.574 respectively), linearly negatively correlated with the creatinine clearance rate (r=-0.755, -0.825, -0.497 and -0.564 respectively). As the renal function deteriorated progressively, the serum levels of CRP, IL-6, IL-10 and TNF-α increased correspondingly. (3) The acute phase protein CRP and inflammatory cytokines IL-6 and TNF-α levels were correlated with those of the anti-inflammatory cytokine IL-10 (r=0.463, 0.546 and 0.402 respectively). Conclusion: The serum acute phase protein CRP, inflammatory cytokines IL-6, TNF-α and anti-inflammatory cytokine IL-10 contents were all gradually increased along with the progression of CRF and these inflammatory mediators were mutually positively correlated with each other. (authors)

  12. Blood-brain barrier hyperpermeability precedes demyelination in the cuprizone model.

    Science.gov (United States)

    Berghoff, Stefan A; Düking, Tim; Spieth, Lena; Winchenbach, Jan; Stumpf, Sina K; Gerndt, Nina; Kusch, Kathrin; Ruhwedel, Torben; Möbius, Wiebke; Saher, Gesine

    2017-12-01

    In neuroinflammatory disorders such as multiple sclerosis, the physiological function of the blood-brain barrier (BBB) is perturbed, particularly in demyelinating lesions and supposedly secondary to acute demyelinating pathology. Using the toxic non-inflammatory cuprizone model of demyelination, we demonstrate, however, that the onset of persistent BBB impairment precedes demyelination. In addition to a direct effect of cuprizone on endothelial cells, a plethora of inflammatory mediators, which are mainly of astroglial origin during the initial disease phase, likely contribute to the destabilization of endothelial barrier function in vivo. Our study reveals that, at different time points of pathology and in different CNS regions, the level of gliosis correlates with the extent of BBB hyperpermeability and edema. Furthermore, in mutant mice with abolished type 3 CXC chemokine receptor (CXCR3) signaling, inflammatory responses are dampened and BBB dysfunction ameliorated. Together, these data have implications for understanding the role of BBB permeability in the pathogenesis of demyelinating disease.

  13. Acquired Demyelinating Syndromes: Focus on Neuromyelitis Optica and childhood-onset Multiple Sclerosis

    NARCIS (Netherlands)

    E.D. van Pelt - Gravesteijn (Daniëlle)

    2016-01-01

    markdownabstractAcquired demyelinating syndromes (ADS) cover a broad spectrum of central nervous system (CNS) inflammatory demyelinating syndromes, of which multiple sclerosis (MS) is the most common subtype. This thesis focuses on two relatively rare clinical subtypes of ADS: neuromyelitis optica

  14. Demyelinizing neurological disease after treatment with tumor necrosis factor alpha-inhibiting agents in a rheumatological outpatient clinic

    DEFF Research Database (Denmark)

    Theibich, Ali; Dreyer, Lene; Magyari, Melinda

    2014-01-01

    Biological treatment with inhibitors of the pro-inflammatory cytokine TNF-alpha has dramatically improved the disease course of several chronic rheumatologic conditions. Adverse events (AEs) are primarily infections and hypersensitivity reactions. Demyelinizing neurological symptoms resembling...... multiple sclerosis (MS) have been described as a rare AE. During about 10-year use of anti TNF-alpha, the Danish Medicines Agency has recorded eight cases of MS like AEs. The objective of this study was to estimate the incidence of demyelinizing AEs both in the central and peripheral nervous system after...... treatment with anti TNF-alpha in a cohort of patients from a large rheumatologic outpatient clinic in Copenhagen. In a 4-year period from January 2008 to December 2011, approximately 550 patients annually were undergoing treatment with anti TNF-alpha inhibitors in our department. We collected data on all...

  15. Chronic inflammatory disease and osteopathy: a systematic review.

    Science.gov (United States)

    Cicchitti, Luca; Martelli, Marta; Cerritelli, Francesco

    2015-01-01

    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. 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. 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. 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 generalize favorable results.

  16. Chronic inflammatory diseases of the rectum and prostate: a review of literature

    Directory of Open Access Journals (Sweden)

    Z. A. Kadyrov

    2016-01-01

    Full Text Available The paper analyzes the Russian and foreign literature on chronic inflammatory diseases of the rectum and chronic prostatitis. The universally known anatomic and vascular relationships of the prostate and rectum indicate that there is a correlation of the development of chronic prostatitis and rectal diseases.

  17. Corpus callosum demyelination associated with acquired stuttering.

    Science.gov (United States)

    Decker, Barbara McElwee; Guitar, Barry; Solomon, Andrew

    2018-04-21

    Compared with developmental stuttering, adult onset acquired stuttering is rare. However, several case reports describe acquired stuttering and an association with callosal pathology. Interestingly, these cases share a neuroanatomical localisation also demonstrated in developmental stuttering. We present a case of adult onset acquired stuttering associated with inflammatory demyelination within the corpus callosum. This patient's disfluency improved after the initiation of immunomodulatory therapy. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  18. Enhanced Gamma Oscillatory Activity in Rats with Chronic Inflammatory Pain

    OpenAIRE

    Wang, Jing; Wang, Jing; Xing, Guo-Gang; Li, Xiaoli; Wan, You

    2016-01-01

    It has been reported that oscillatory gamma activity participates in brief acute pain and tonic ongoing pain. It is of great interest to determine whether the gamma activity is involved in chronic pain since chronic pain is a more severe pathological condition characterized by pain persistency. To investigate the oscillatory gamma activity in chronic pain, in the present study, we recorded spontaneous electrocorticogram (ECoG) signals during chronic pain development in rats with chronic infla...

  19. Regional oligodendrocytopathy and astrocytopathy precede myelin loss and blood-brain barrier disruption in a murine model of osmotic demyelination syndrome.

    Science.gov (United States)

    Bouchat, Joanna; Couturier, Bruno; Marneffe, Catherine; Gankam-Kengne, Fabrice; Balau, Benoît; De Swert, Kathleen; Brion, Jean-Pierre; Poncelet, Luc; Gilloteaux, Jacques; Nicaise, Charles

    2018-03-01

    The osmotic demyelination syndrome (ODS) is a non-primary inflammatory disorder of the central nervous system myelin that is often associated with a precipitous rise of serum sodium concentration. To investigate the physiopathology of ODS in vivo, we generated a novel murine model based on the abrupt correction of chronic hyponatremia. Accordingly, ODS mice developed impairments in brainstem auditory evoked potentials and in grip strength. At 24 hr post-correction, oligodendrocyte markers (APC and Cx47) were downregulated, prior to any detectable demyelination. Oligodendrocytopathy was temporally and spatially correlated with the loss of astrocyte markers (ALDH1L1 and Cx43), and both with the brain areas that will develop demyelination. Oligodendrocytopathy and astrocytopathy were confirmed at the ultrastructural level and culminated with necroptotic cell death, as demonstrated by pMLKL immunoreactivity. At 48 hr post-correction, ODS brains contained pathognomonic demyelinating lesions in the pons, mesencephalon, thalamus and cortical regions. These damages were accompanied by blood-brain barrier (BBB) leakages. Expression levels of IL-1β, FasL, TNFRSF6 and LIF factors were significantly upregulated in the ODS lesions. Quiescent microglial cells type A acquired an activated type B morphology within 24 hr post-correction, and reached type D at 48 hr. In conclusion, this murine model of ODS reproduces the CNS demyelination observed in human pathology and indicates ambiguous causes that is regional vulnerability of oligodendrocytes and astrocytes, while it discards BBB disruption as a primary cause of demyelination. This study also raises new queries about the glial heterogeneity in susceptible brain regions as well as about the early microglial activation associated with ODS. © 2017 Wiley Periodicals, Inc.

  20. Role of Transient Receptor Potential Vanilloid 1 in Electroacupuncture Analgesia on Chronic Inflammatory Pain in Mice

    Directory of Open Access Journals (Sweden)

    Jun Yang

    2017-01-01

    Full Text Available Chronic inflammatory pain may result from peripheral tissue injury or inflammation, increasing the release of protons, histamines, adenosine triphosphate, and several proinflammatory cytokines and chemokines. Transient receptor potential vanilloid 1 (TRPV1 is known to be involved in acute to subacute neuropathic and inflammatory pain; however, its exact mechanisms in chronic inflammatory pain are not elucidated. Our results showed that EA significantly reduced chronic mechanical and thermal hyperalgesia in the chronic inflammatory pain model. Chronic mechanical and thermal hyperalgesia were also abolished in TRPV1−/− mice. TRPV1 increased in the dorsal root ganglion (DRG and spinal cord (SC at 3 weeks after CFA injection. The expression levels of downstream molecules such as pPKA, pPI3K, and pPKC increased, as did those of pERK, pp38, and pJNK. Transcription factors (pCREB and pNFκB and nociceptive ion channels (Nav1.7 and Nav1.8 were involved in this process. Inflammatory mediators such as GFAP, S100B, and RAGE were also involved. The expression levels of these molecules were reduced in EA and TRPV1−/− mice but not in the sham EA group. Our data provided evidence to support the clinical use of EA for treating chronic inflammatory pain.

  1. Demyelinating disease masquerading as a surgical problem: a case series

    Directory of Open Access Journals (Sweden)

    Awang Saufi M

    2009-08-01

    Full Text Available Abstract Introduction We report three cases of demyelinating disease with tumor-like presentation. This information is particularly important to both neurosurgeons and neurologists who should be aware that inflammatory demyelinating diseases can present as a mass lesion, which is indistinguishable from a tumor, both clinically and radiologically, especially when there is no evidence of temporal dissemination of this disease. Case presentation The first patient was a 42-year-old Malay woman who developed subacute onset of progressive quadriparesis with urinary incontinence. Magnetic resonance imaging of her spine showed an intramedullary lesion at the C5-C7 level. She was operated on and biopsy was suggestive of a demyelinating disease. Retrospective history discovered two episodes of acute onset of neurological deficits with partial recovery and magnetic resonance imaging of her brain revealed demyelinating plaques in the centrum semiovale. The second patient was a 16-year-old Malay boy who presented with symptoms of raised intracranial pressure. A computed tomography brain scan revealed obstructive hydrocephalus with a lesion adjacent to the fourth ventricle. An external ventricular drainage was inserted. Subsequently, a stereotactic biopsy was taken and histopathology was reported as demyelination. Retrospective history revealed similar episodes with full recovery in between episodes. The third case was a 28-year-old Malay man who presented with acute bilateral visual loss and confusion. Magnetic resonance imaging of his brain showed a large mass lesion in the right temporoparietal region. Biopsy was consistent with demyelinating disease. Reexamination of the patient revealed bilateral papillitis and not papilledema. Visual evoked potential was prolonged bilaterally. In all three cases, lumbar puncture for cerebrospinal fluid study was not carried out due to lack of patient consent. Conclusions These cases illustrate the importance of

  2. Prevalence of chronic diseases at the onset of inflammatory arthritis: a population-based study.

    NARCIS (Netherlands)

    Ursum, J.; Korevaar, J.C.; Twisk, J.W.R.; Peters, M.J.L.; Schellevis, F.G.; Nurmohamed, M.T.; Nielen, M.M.J.

    2013-01-01

    Objective. Little is known about the presence of chronic morbidity in inflammatory arthritis (IA) patients at disease onset. Previous studies have been mainly performed in established IA patients or they focus on isolated co-morbid diseases. Our aim was to determine the prevalence of chronic

  3. Non-steroidal anti-inflammatory drugs for chronic low back pain

    NARCIS (Netherlands)

    W.T.M. Enthoven (Wendy); P.D.D.M. Roelofs (Pepijn); R.A. Deyo (Richard); M.W. van Tulder (Maurits); B.W. Koes (Bart)

    2016-01-01

    textabstractBackground: Chronic back pain is an important health problem. Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to treat people with low back pain, especially people with acute back pain. Short term NSAID use is also recommended for pain relief in people with chronic back

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

    Science.gov (United States)

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

    2018-03-01

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

  5. Chronic Inflammatory Diseases and Atherosclerotic Cardiovascular Disease: Innocent Bystanders or Partners in Crime?

    Science.gov (United States)

    Hansen, Peter Riis

    2018-01-01

    Inflammation plays a significant role in atherosclerosis and cardiovascular disease (CVD). Patients with chronic inflammatory diseases are at increased risk of CVD, but it is debated whether this association is causal or dependent on shared risk factors, other exposures, genes, and/or inflammatory pathways. The current review summarizes epidemiological, clinical, and experimental data supporting the role of shared inflammatory mechanisms between atherosclerotic CVD and rheumatoid arthritis, psoriasis, inflammatory bowel disease, and periodontitis, respectively, and provides insights to future prospects in this area of research. Awareness of the role of inflammation in CVD in patients with chronic inflammatory diseases and the potential for anti-inflammatory therapy, e.g., with tumor necrosis factor-α inhibitors, to also reduce atherosclerotic CVD has evolved into guideline- based recommendations. These include regular CVD risk assessment, aggressive treatment of traditional CVD risk factors, and recognition of reduced CVD as an added benefit of strict inflammatory disease control. At present, chronic inflammatory diseases would appear to qualify as partners in crime and not merely innocent bystanders to CVD. However, definite incremental contributions of inflammation versus effects of the complex interplay with other CVD risk factors may never be fully elucidated and for the foreseeable future, inflammation is posed to maintain its current position as both a marker and a maker of CVD, with clinical utility both for identification of patient at risk of CVD and as target for therapy to reduce CVD. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  6. Diffusion-weighted imaging in acute demyelinating myelopathy

    International Nuclear Information System (INIS)

    Zecca, Chiara; Cereda, Carlo; Tschuor, Silvia; Staedler, Claudio; Nadarajah, Navarajah; Bassetti, Claudio L.; Gobbi, Claudio; Wetzel, Stephan; Santini, Francesco

    2012-01-01

    Diffusion-weighted imaging (DWI) has become a reference MRI technique for the evaluation of neurological disorders. Few publications have investigated the application of DWI for inflammatory demyelinating lesions. The purpose of the study was to describe diffusion-weighted imaging characteristics of acute, spinal demyelinating lesions. Six consecutive patients (two males, four females; aged 28-64 years) with acute spinal cord demyelinating lesions were studied in a prospective case series design from June 2009 to October 2010. We performed magnetic resonance imaging studies from 2 to 14 days from symptom onset on the patients with relapsing remitting multiple sclerosis (n = 3) or clinically isolated syndrome (n = 3). Main outcome measures were diffusion-weighted imaging and apparent diffusion coefficient pattern (ADC) of acute spinal cord demyelinating lesions. All spinal lesions showed a restricted diffusion pattern (DWI+/ADC-) with a 24% median ADC signal decrease. A good correlation between clinical presentation and lesion site was observed. Acute demyelinating spinal cord lesions show a uniform restricted diffusion pattern. Clinicians and neuro-radiologists should be aware that this pattern is not necessarily confirmatory for an ischaemic aetiology. (orig.)

  7. Diffusion-weighted imaging in acute demyelinating myelopathy

    Energy Technology Data Exchange (ETDEWEB)

    Zecca, Chiara; Cereda, Carlo; Tschuor, Silvia; Staedler, Claudio; Nadarajah, Navarajah; Bassetti, Claudio L.; Gobbi, Claudio [Ospedale Regionale di Lugano, Servizio di Neurologia e Neuroradiologia, Neurocenter of Southern Switzerland, Lugano (Switzerland); Wetzel, Stephan [Swiss Neuro Institute (SNI), Abteilung fuer Neuroradiologie, Hirslanden Klinik Zuerich, Zuerich (Switzerland); Santini, Francesco [University of Basel Hospital, Division of Radiological Physics, Basel (Switzerland)

    2012-06-15

    Diffusion-weighted imaging (DWI) has become a reference MRI technique for the evaluation of neurological disorders. Few publications have investigated the application of DWI for inflammatory demyelinating lesions. The purpose of the study was to describe diffusion-weighted imaging characteristics of acute, spinal demyelinating lesions. Six consecutive patients (two males, four females; aged 28-64 years) with acute spinal cord demyelinating lesions were studied in a prospective case series design from June 2009 to October 2010. We performed magnetic resonance imaging studies from 2 to 14 days from symptom onset on the patients with relapsing remitting multiple sclerosis (n = 3) or clinically isolated syndrome (n = 3). Main outcome measures were diffusion-weighted imaging and apparent diffusion coefficient pattern (ADC) of acute spinal cord demyelinating lesions. All spinal lesions showed a restricted diffusion pattern (DWI+/ADC-) with a 24% median ADC signal decrease. A good correlation between clinical presentation and lesion site was observed. Acute demyelinating spinal cord lesions show a uniform restricted diffusion pattern. Clinicians and neuro-radiologists should be aware that this pattern is not necessarily confirmatory for an ischaemic aetiology. (orig.)

  8. Use of nonsteroidal anti-inflammatory drugs prior to chronic renal replacement therapy initiation

    DEFF Research Database (Denmark)

    Kristensen, Søren Lund; Fosbøl, Emil L; Kamper, Anne-Lise

    2012-01-01

    PURPOSE: Nonsteroidal anti-inflammatory drugs (NSAIDs) may be associated with severe renal complications, including acute renal failure, reduced glomerular filtration rate and interstitial nephritis. Caution against NSAIDs is therefore recommended in advanced chronic kidney disease. In this study......, we examined NSAID use, aetiology and comorbidity among a national cohort of patients before the initiation of chronic renal replacement therapy (RRT). METHODS: Patients initiated on chronic RRT in the period 1997-2006 were identified in the Danish National Registry on Regular Dialysis...

  9. Defining the neurotoxin derived illness chronic ciguatera using markers of chronic systemic inflammatory disturbances: a case/control study.

    Science.gov (United States)

    Shoemaker, Ritchie C; House, Dennis; Ryan, James C

    2010-01-01

    Ciguatoxins are extremely potent neurotoxins, produced by tropical marine dinoflagellates, that persistently enter into our food web. Over 100,000 people annually experience acute ciguatera poisoning from consuming toxic fish. Roughly 5% of these victims will develop chronic ciguatera (CC), a widespread, multisymptom, multisystem, chronic illness that can last tens of years. CC is marked by disproportionate disability and non-specific refractory symptoms such as fatigue, cognitive deficits and pain, and is suggestive of other illnesses. Its unknown pathophysiology makes both diagnosis and treatment difficult. We wanted to compare objective parameters of visual contrast sensitivity testing, measures of innate immune response and genetic markers in cases to controls to assess the potential for the presence of persistent inflammatory parameters that are demonstrated in other biotoxin associated illnesses at a single specialty clinic. Using 59 CC cases and 59 controls we present in retrospective review, in all cases, abnormalities in immune responses paralleling the chronic systemic inflammatory response syndrome seen in several other chronic diseases. This study defines a preliminary case definition using medical history, total symptoms, visual contrast sensitivity, HLA DR genotype analysis, reduction of regulatory neuropeptides VIP and MSH, and multiple measures of inflammatory immune response, especially C4a and TGFβ1, thereby providing a basis for identification and targeted therapy. CC provides a model for chronic human illness associated with initiation of inflammatory responses by biologically produced neurotoxins. Copyright © 2010 Elsevier Inc. All rights reserved.

  10. Analysis of relationship between demyelinating lesions and myelin basic protein in pancreatic encephalopathy

    Directory of Open Access Journals (Sweden)

    HUANG Boru

    2015-05-01

    Full Text Available Pancreatic encephalopathy (PE is one of the severe complications of severe acute pancreatitis (SAP. Early diagnosis mostly depends on the history of disease as well as clinical symptoms and signs. PE progresses rapidly and is often complicated by multiple organ dysfunction, and it may finally develop into multiple organ failure with a high fatality rate if not treated in time. It is currently known that demyelination is one of the important pathological features of this disease, with fat-soluble demyelination of cerebral gray matter and white matter, as well as inflammatory changes such as hemorrhage and edema. The target antigen of demyelinating lesions, however, is myelin basic protein (MBP. This paper reviews the changes in MBP levels in the demyelinating lesions of the central nervous system among PE patients, with the purpose of providing clues for the early diagnosis and prognostic study of demyelinating lesions in PE.

  11. Inflammatory biomarkers and exacerbations in chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Thomsen, Mette; Ingebrigtsen, Truls Sylvan; Marott, Jacob Louis

    2013-01-01

    Exacerbations of respiratory symptoms in chronic obstructive pulmonary disease (COPD) have profound and long-lasting adverse effects on patients.......Exacerbations of respiratory symptoms in chronic obstructive pulmonary disease (COPD) have profound and long-lasting adverse effects on patients....

  12. Inflammatory biomarkers and comorbidities in chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Thomsen, Mette; Dahl, Morten; Lange, Peter

    2012-01-01

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

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

    African Journals Online (AJOL)

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

  14. Current drug therapies for rosacea: a chronic vascular and inflammatory skin disease.

    Science.gov (United States)

    Feldman, Steven R; Huang, William W; Huynh, Tu T

    2014-06-01

    Rosacea is a chronic skin disorder that presents with abnormal vascular and inflammatory conditions. Clinical manifestations include flushing, facial erythema, inflammatory papules and pustules, telangiectasias, edema, and watery or irritated eyes. To discuss the evolving pathophysiology of rosacea, factors involved in promoting the chronic vascular and inflammatory abnormalities seen in rosacea, and the available drug therapies for the condition. Chronic inflammation and vascular changes are believed to be underlying factors in the pathophysiology of rosacea. Aberrant cathelicidin expression, elevated kallikrein 5 (KLK5) proteolytic activity, and altered toll-like receptor 2 (TLR2) expression have been reported in rosacea skin leading to the production of proinflammatory cytokines. Until recently, drug therapies only targeted the inflammatory lesions (papules and pustules) and transient erythema associated with these inflammatory lesions of rosacea. Brimonidine tartrate gel 0.5% was recently approved for the treatment of persistent (nontransient) facial erythema of rosacea, acting primarily on the cutaneous vascular component of the disease. Rosacea is a chronic vascular and inflammatory skin disease. Understanding the role of factors that trigger the onset of rosacea symptoms and exacerbate the condition is crucial in treating this skin disease.

  15. Acute and chronic stress and the inflammatory response in hyperprolactinemic rats.

    Science.gov (United States)

    Ochoa-Amaya, J E; Malucelli, B E; Cruz-Casallas, P E; Nasello, A G; Felicio, L F; Carvalho-Freitas, M I R

    2010-01-01

    Prolactin (PRL), a hormone produced by the pituitary gland, has multiple physiological functions, including immunoregulation. PRL can also be secreted in response to stressful stimuli. During stress, PRL has been suggested to oppose the immunosuppressive effects of inflammatory mediators. Therefore, the aim of the present study was to analyze the effects of short- and long-term hyperprolactinemia on the inflammatory response in rats subjected to acute or chronic cold stress. Inflammatory edema was induced by carrageenan in male rats, and hyperprolactinemia was induced by injections of the dopamine receptor antagonist domperidone. The volume of inflammatory edema was measured by plethysmography after carrageenan injection. Additionally, the effects of hyperprolactinemia on body weight and serum corticosterone levels were evaluated. Five days of domperidone-induced hyperprolactinemia increased the volume of inflammatory edema. No differences in serum corticosterone levels were observed between groups. No significant differences were found among 30 days domperidone-induced hyperprolactinemic animals subjected to acute stress and the inflammatory response observed in chronic hyperprolactinemic animals subjected to chronic stress. The results suggest that short-term hyperprolactinemia has pro-inflammatory effects. Because such an effect was not observed in long-term hyperprolactinemic animals, PRL-induced tolerance seems likely. We suggest that short-term hyperprolactinemia may act as a protective factor in rats subjected to acute stress. These data suggest that hyperprolactinemia and stress interact differentially according to the time period. Copyright 2010 S. Karger AG, Basel.

  16. PPARγ as a Potential Target to Treat Airway Mucus Hypersecretion in Chronic Airway Inflammatory Diseases

    Directory of Open Access Journals (Sweden)

    Yongchun Shen

    2012-01-01

    Full Text Available Airway mucus hypersecretion (AMH is a key pathophysiological feature of chronic airway inflammatory diseases such as bronchial asthma, cystic fibrosis, and chronic obstructive pulmonary disease. AMH contributes to the pathogenesis of chronic airway inflammatory diseases, and it is associated with reduced lung function and high rates of hospitalization and mortality. It has been suggested that AMH should be a target in the treatment of chronic airway inflammatory diseases. Recent evidence suggests that a key regulator of airway inflammation, hyperresponsiveness, and remodeling is peroxisome proliferator-activated receptor gamma (PPARγ, a ligand-activated transcription factor that regulates adipocyte differentiation and lipid metabolism. PPARγ is expressed in structural, immune, and inflammatory cells in the lung. PPARγ is involved in mucin production, and PPARγ agonists can inhibit mucin synthesis both in vitro and in vivo. These findings suggest that PPARγ is a novel target in the treatment of AMH and that further work on this transcription factor may lead to new therapies for chronic airway inflammatory diseases.

  17. Inflammatory fatigue and sickness behaviour - lessons for the diagnosis and management of chronic fatigue syndrome.

    Science.gov (United States)

    Arnett, S V; Clark, I A

    2012-12-10

    Persistent and severe fatigue is a common part of the presentation of a diverse range of disease processes. There is a growing body of evidence indicating a common inflammatory pathophysiology underlying many conditions where fatigue is a primary patient concern, including chronic fatigue syndrome. This review explores current models of how inflammatory mediators act on the central nervous system to produce fatigue and sickness behaviour, and the commonality of these processes in conditions as diverse as surgical trauma, infection, various cancers, inflammatory bowel disease, connective tissue diseases and autoimmune diseases. We also discuss evidence indicating chronic fatigue syndrome may have important pathophysiological similarities with cytokine mediated sickness behaviour, and what lessons can be applied from sickness behaviour to chronic fatigue syndrome with regards to the diagnosis and management. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. Evaluation of anti-inflammatory effect of statins in chronic periodontitis

    OpenAIRE

    Snophia Suresh; Satya Narayana; P Jayakumar; Uma Sudhakar; V Pramod

    2013-01-01

    Objectives: Statins are the group of lipid-lowering drugs commonly used to control cardiovascular and cerebrovascular diseases. Statins have potential anti-inflammatory effect by blocking the intermediate metabolites of the mevalonate pathway. The objective of this study was to evaluate the anti-inflammatory effect of statin medication in chronic periodontitis patients. Materials and Methods: Thirty patients of age group between 40 and 60 years were selected from the outpatient pool of De...

  19. A 17 year-old girl with a demyelinating disease requiring mechanical ventilation: a case report

    Directory of Open Access Journals (Sweden)

    Katsenos Chrysostomos

    2013-01-01

    Full Text Available Abstract Background Demyelinating diseases cause destruction of the myelin sheath, while axons are relatively spared. Pathologically, demyelination can be the result of an inflammatory process, viral infection, acquired metabolic derangement and ischemic insult. Three diseases that can cause inflammatory demyelination of the CNS are: Multiple sclerosis (MS, Acute disseminated encephalomyelitis (ADEM and Acute hemorrhagic leucoencephalitis. Differentiation is not always easy and there is considerable overlaping. Data about adults with acute demyelination requiring ICU admission is limited. Case presentation A 17 year old Greek female was hospitalised in the ICU because of acute respiratory failure requiring mechanical ventilation. She had a history of febrile disease one month before, acute onset of paraplegia, diplopia, progressive arm weakness and dyspnea. Her consciousness was not impaired. A demyelinating central nervous system (CNS disease, possibly post infectious encephalomyelitis (ADEM was the underlying condition. The MRI of the brain disclosed diffused expanded cerebral lesions involving the optic nerve, basal ganglia cerebellum, pons and medulla oblongata. There was also extended involvement of the cervical and thoracic part of the spinal cord. CSF leukocyte count was elevated with lymphocyte predominance. The patient required mechanical ventilation for two months. Then she was transferred to a rehabilitation centre. Three years later she remains paraplegic. Since then she has not suffered any other demyelination attack. Conclusions Demyelinating diseases can cause acute respiratory failure when the spinal cord is affected. Severe forms of these diseases, making necessary ICU admission, is less frequently reported. Intensivists should be aware of the features of these rare diseases.

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

    DEFF Research Database (Denmark)

    Larsen, Jeppe Madura

    2017-01-01

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

  1. Natural Killer Cells in the Orchestration of Chronic Inflammatory Diseases

    Directory of Open Access Journals (Sweden)

    Luca Parisi

    2017-01-01

    Full Text Available Inflammation, altered immune cell phenotype, and functions are key features shared by diverse chronic diseases, including cardiovascular, neurodegenerative diseases, diabetes, metabolic syndrome, and cancer. Natural killer cells are innate lymphoid cells primarily involved in the immune system response to non-self-components but their plasticity is largely influenced by the pathological microenvironment. Altered NK phenotype and function have been reported in several pathological conditions, basically related to impaired or enhanced toxicity. Here we reviewed and discussed the role of NKs in selected, different, and “distant” chronic diseases, cancer, diabetes, periodontitis, and atherosclerosis, placing NK cells as crucial orchestrator of these pathologic conditions.

  2. CD64: An Attractive Immunotherapeutic Target for M1-type Macrophage Mediated Chronic Inflammatory Diseases

    Directory of Open Access Journals (Sweden)

    Olusiji A. Akinrinmade

    2017-09-01

    Full Text Available To date, no curative therapy is available for the treatment of most chronic inflammatory diseases such as atopic dermatitis, rheumatoid arthritis, or autoimmune disorders. Current treatments require a lifetime supply for patients to alleviate clinical symptoms and are unable to stop the course of disease. In contrast, a new series of immunotherapeutic agents targeting the Fc γ receptor I (CD64 have emerged and demonstrated significant clinical potential to actually resolving chronic inflammation driven by M1-type dysregulated macrophages. This subpopulation plays a key role in the initiation and maintenance of a series of chronic diseases. The novel recombinant M1-specific immunotherapeutics offer the prospect of highly effective treatment strategies as they have been shown to selectively eliminate the disease-causing macrophage subpopulations. In this review, we provide a detailed summary of the data generated, together with the advantages and the clinical potential of CD64-based targeted therapies for the treatment of chronic inflammatory diseases.

  3. Iron deficiency across chronic inflammatory conditions: International expert opinion on definition, diagnosis, and management.

    Science.gov (United States)

    Cappellini, Maria Domenica; Comin-Colet, Josep; de Francisco, Angel; Dignass, Axel; Doehner, Wolfram; Lam, Carolyn S; Macdougall, Iain C; Rogler, Gerhard; Camaschella, Clara; Kadir, Rezan; Kassebaum, Nicholas J; Spahn, Donat R; Taher, Ali T; Musallam, Khaled M

    2017-10-01

    Iron deficiency, even in the absence of anemia, can be debilitating, and exacerbate any underlying chronic disease, leading to increased morbidity and mortality. Iron deficiency is frequently concomitant with chronic inflammatory disease; however, iron deficiency treatment is often overlooked, partially due to the heterogeneity among clinical practice guidelines. In the absence of consistent guidance across chronic heart failure, chronic kidney disease and inflammatory bowel disease, we provide practical recommendations for iron deficiency to treating physicians: definition, diagnosis, and disease-specific diagnostic algorithms. These recommendations should facilitate appropriate diagnosis and treatment of iron deficiency to improve quality of life and clinical outcomes. © 2017 The Authors American Journal of Hematology Published by Wiley Periodicals, Inc.

  4. Chronic inflammatory cells and damaged limbal cells in pterygium

    African Journals Online (AJOL)

    EB

    2013-09-03

    Sep 3, 2013 ... Objective: To explain chronic inflammation in pterygium, and to clarify whether damaged limbal basal epithelial cells were ..... Jiang Y, Goldberg ID, Shi YE. Complex roles of tissue inhibitors of metalloproteinases in cancer. Oncogene 2002; 21: 2245-2252. 6. Kato S, Aoshima H, Saitoh Y, Miwa N. Fullerene-.

  5. Blood Dendritic Cells: Canary in the Coal Mine to Predict Chronic Inflammatory Disease?

    Directory of Open Access Journals (Sweden)

    Brodie eMiles

    2014-01-01

    Full Text Available The majority of risk factors for chronic inflammatory diseases are unknown. This makes personalized medicine for assessment, prognosis, and choice of therapy very difficult. It is becoming increasingly clear, however, that low-grade subclinical infections may be an underlying cause of many chronic inflammatory diseases and thus may contribute to secondary outcomes (e.g. cancer. Many diseases are now categorized as inflammatory-mediated diseases that stem from a dysregulation in host immunity. There is a growing need to study the links between low-grade infections, the immune responses they elicit, and how this impacts overall health. One such link explored in detail here is the extreme sensitivity of myeloid dendritic cells (mDC in peripheral blood to chronic low-grade infections and the role that these mDCs play in arbitrating the resulting immune responses. We find that emerging evidence supports a role for pathogen-induced mDCs in chronic inflammation leading to increased risk of secondary clinical disease. The mDCs that are elevated in the blood as a result of low-grade bacteremia often do not trigger a productive immune response, but can disseminate the pathogen throughout the host. This aberrant trafficking of mDCs can accelerate systemic inflammatory disease progression. Conversely, restoration of DC homeostasis may aid in pathogen elimination and minimize dissemination. Thus it would seem prudent when assessing chronic inflammatory disease risk to consider blood mDC numbers, and the microbial content (microbiome and activation state of these mDCs. These may provide important clues (the canary in the coal mine of high inflammatory disease risk. This will facilitate development of novel immunotherapies to eliminate such smoldering infections in atherosclerosis, cancer, rheumatoid arthritis, and pre-eclampsia.

  6. Evolutionary medicine and chronic inflammatory state--known and new concepts in pathophysiology.

    Science.gov (United States)

    Straub, Rainer H

    2012-05-01

    During the last 10 years, a series of exciting observations has led to a new theory of pathophysiology using insights from evolutionary biology and neuroendocrine immunology to understand the sequelae of chronic inflammatory disease. According to this theory, disease sequelae can be explained based on redirection of energy-rich fuels from storage organs to the activated immune system. These disease sequelae are highly diverse and include the following: sickness behavior, anorexia, malnutrition, muscle wasting-cachexia, cachectic obesity, insulin resistance with hyperinsulinemia, dyslipidemia, increase of adipose tissue near inflamed tissue, alterations of steroid hormone axes, elevated sympathetic tone and local sympathetic nerve fiber loss, decreased parasympathetic tone, hypertension, inflammation-related anemia, and osteopenia. Since these disease sequelae can be found in many animal models of chronic inflammatory diseases with mammals (e.g., monkeys, mice, rats, rabbits, etc.), the evolutionary time line goes back at least 70 million years. While the initial version of this theory could explain prominent sequelae of chronic inflammatory disease, it did not however address two features important in the pathogenesis of immune-mediated diseases: the time point when an acute inflammatory disease becomes chronic, and the appearance of hypertension in chronic inflammation. To address these aspects more specifically, a new version of the theory has been developed. This version defines more precisely the moment of transition from acute inflammatory disease to chronic inflammatory disease as a time in which energy stores become empty (complete energy consumption). Depending on the amount of stored energy, this time point can be calculated to be 19-43 days. Second, the revised theory addresses the mechanisms of essential hypertension since, on the basis of water loss, acute inflammatory diseases can stimulate water retention using a positively selected water retention

  7. Cerebrospinal fluid analysis in the context of CNS demyelinating diseases

    Directory of Open Access Journals (Sweden)

    Sandro Luiz de Andrade Matas

    2013-09-01

    Full Text Available The central nervous system demyelinating diseases are a group of disorders with different etiologies, characterized by inflammatory lesions that are associated with loss of myelin and eventually axonal damage. In this group the most studied ones are multiple sclerosis (MS, neuromyelitis optic (NMO and acute disseminated encephalomyelitis (ADEM. The cerebrospinal fluid is essential to differentiate between these different syndromes and to define multiple sclerosis, helping to assess the probability of Clinical Isolated Syndrome turn into multiple sclerosis.

  8. [Travel advice and vaccinations in patients with chronic inflammatory diseases: the earlier, the better

    NARCIS (Netherlands)

    Mast, Q. de; Keuter, M.; Thiel, P.P. van; Ven, A.J. van der

    2014-01-01

    The number of patients with chronic inflammatory diseases who have been travelling to the tropics or subtropics has been rising. Use of immunomodulating drugs increases the risk for infectious diseases and may reduce seroprotection rates following vaccination. In addition, live vaccines, such as the

  9. Anti-proline-glycine-proline or antielastin autoantibodies are not evident in chronic inflammatory lung disease.

    LENUS (Irish Health Repository)

    Greene, Catherine M

    2010-01-01

    In patients with chronic inflammatory lung disease, pulmonary proteases can generate neoantigens from elastin and collagen with the potential to fuel autoreactive immune responses. Antielastin peptide antibodies have been implicated in the pathogenesis of tobacco-smoke-induced emphysema. Collagen-derived peptides may also play a role.

  10. Evaluation of anti-inflammatory effect of statins in chronic periodontitis.

    Science.gov (United States)

    Suresh, Snophia; Narayana, Satya; Jayakumar, P; Sudhakar, Uma; Pramod, V

    2013-01-01

    Statins are the group of lipid-lowering drugs commonly used to control cardiovascular and cerebrovascular diseases. Statins have potential anti-inflammatory effect by blocking the intermediate metabolites of the mevalonate pathway. The objective of this study was to evaluate the anti-inflammatory effect of statin medication in chronic periodontitis patients. Thirty patients of age group between 40 and 60 years were selected from the outpatient pool of Department of Periodontics, Thaimoogambigai Dental College and Hospital, Chennai. Thirty patients selected were grouped into two groups, Group-I consists of patients with generalized chronic periodontitis and on statin medication and Group-II consists of patients with generalized chronic periodontitis. Clinical parameters were recorded and gingival crevicular fluid (GCF) samples were analyzed for interleukin (IL)-1β using commercially available enzyme-linked immunosorbent assay. The mean GCF IL-1β levels in generalized chronic periodontitis patients who are on statin medication (Group-I) were lower than the generalized chronic periodontitis patients without statin medication (Group-II). Reduction of GCF IL-1β levels in statin users indicate that statins have anti-inflammatory effect on periodontal disease.

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

    Directory of Open Access Journals (Sweden)

    Caroline Marcantonio Ferreira

    2014-01-01

    Full Text Available 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.

  12. Radiological and scintigraphic findings in patients with a clinical history of chronic inflammatory back pain

    International Nuclear Information System (INIS)

    Goei The, H.S.; Lemmens, A.J.; Goedhard, G.; Lokkerbol, H.; Rahmy, A.; Linden, S.M. van der; Cats, A.; Steven, M.M.

    1985-01-01

    The prevalence of radiological abnormalities of the sacroiliac joints, the manubriosternal joint, and the lumbar spine were assessed, and quantitative sacroiliac scintigraphy was performed in 151 patients with a history of chronic inflammatory back pain and in 31 controls with non-inflammatory back pain. Sacroiliitis was found in 124 patients (82%), manubriosternal lesions in 84 patients (56%), and lesions of the lumbar spine in 58 patients (38%). In 19 patients (13%), manubriosternal lesions provided the sole radiological abnormality and in five patients (3%) no radiological abnormality could be demonstrated at any of these sites. Quantitative sacroiliac scintigraphy showed increased values in 69 of 137 patients examined (50%), but also in 10 out of 12 control patients with disc degeneration (83%) and is, therefore, nonspecific for inflammatory lesions. Radiological examination of the manubriosternal joint is recommended in patients with inflammatory back pain without radiographic evidence of sacroiliitis. (orig.)

  13. Effect of intravenous immunoglobulin in Guilain-Barre syndrome, myasthenia gravis and chronic idiopathic demyelinative polyneuropathy, A survey in Imam Khomeini Hospital

    Directory of Open Access Journals (Sweden)

    Qaffarpoor M

    1999-09-01

    Full Text Available With retrospective evaluation of 44 patients suffering from Guilan-Barre Syndrome (GBS, Chronic Idiopathic Demtyelinative Polyradiculoneuropathy (CIDP and Myasthenia Gravis (MG treated with intravenous immunoglobulin, we found following results: 1 Initial symptoms of improvement on forth or fifth days. 2 Maximum recovery for CIDP and MG were after 16-24 and 3-11 days, respectively. 3 No major complication, but mild side effects in 32% of patients. 4 In patients with GBS one grade improvement achieved after 8-30 days. 5 Intravenous immunoglobulin (IVIG plus plasmapheresis had no advantages over IVIG alone. 6 No reasonable conclusion about relapsing rate and duration of response due to follow up restrictions.

  14. Chronic inflammatory disorders of the gastrointestinal tract of companion animals.

    Science.gov (United States)

    Cave, N J

    2003-12-01

    In the inflammatory bowel diseases (IBD) that affect dogs and cats there appears to be dysregulation of normal mucosal immunity, characterised by polyclonal lymphocytic infiltrates which are presumably specific for luminal antigens. There is an absence of a classical polarisation of either T-helper (Th) 1 or Th2 cytokine responses, although increased expression of mRNA for interleukin (IL) 2 and IL-12p40 and a shift towards mucosal immunoglobulin (Ig) G production are consistent findings, whilst variable responses are seen in tumour necrosis factor-alpha (TNF-alpha), IL-1, IL-4, IL-6, and interferon-gamma (IFN-gamma). Increased mucosal permeability and deranged intestinal motility are common sequelae. Despite obvious similarities with Crohn's disease and ulcerative colitis in humans, important differences exist. Of these, the diffuse superficial nature but with no Th1 or Th2 bias, and the prevalence of proximal small intestinal disease are notable. Potential hypotheses for these disparities include specific differences in the types or locations of agonistic gut flora, diffuse abnormalities in microbial-host interactions, a greater importance of diet, or anatomical or cellular differences in mucosal immune responses. Although specific pathogens and genetic susceptibilities may be involved, quantitative or qualitative changes in the normal flora or abnormal responses to a normal flora are more likely to be involved in the immunopathogenesis. Dietary influences include a large source of antigen, promotion of abnormal microbial growth through Maillard compounds within canned diets, and specific macro- and micronutrient deficiencies. Although dependent on a histopathological diagnosis, limitations of biopsies procured endoscopically, lack of histopathological standardisation and difficulty distinguishing inflammation from neoplasia remain significant problems. Clinician-pathologist dialogue, immunohistochemistry, cytokine profiling and lymphocyte clonality assessment

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

    Science.gov (United States)

    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.

  16. Measurement of inflammatory cytokines and thrombomodulin in chronic subdural hematoma.

    Science.gov (United States)

    Kitazono, Masatoshi; Yokota, Hiroyuki; Satoh, Hidetaka; Onda, Hidetaka; Matsumoto, Gaku; Fuse, Akira; Teramoto, Akira

    2012-01-01

    Inflammation and the coagulation system may influence the genesis of chronic subdural hematoma (CSDH). The appearance of CSDH on computed tomography (CT) varies with the stage of the hematoma. This study investigated the pathogenesis and the recurrence of CSDH by comparing cytokine levels with the CT features of CSDH in 26 patients with 34 CSDHs who underwent single burr-hole surgery at our hospital between October 2004 and November 2006. The hematoma components removed during the procedure were examined, and the hematoma serum levels of cytokines measured such as thrombomodulin (TM), interleukin-6 (IL-6), tumor necrosis factor-α (TNFα), and interleukin-10 (IL-10). Using CT, mixed density hematomas were distinguished from other homogeneous hematomas, and found that the TM level was significantly higher in mixed density hematomas than in homogeneous hematomas (p = 0.043). Mixed density hematomas were classified into three subtypes (laminar, separated, and trabecular hematomas). The TM level was significantly higher in laminar and separated hematomas than in other hematomas (p = 0.01). The levels of IL-6, TNFα, and IL-10 were extremely high, but showed no significant differences in relation to the CT features. Mixed density hematomas had high recurrence rate, as reported previously, and TM level was high in mixed density hematomas such as laminar and separated mixed density hematomas. The present findings suggest that the types of CSDH associated with high TM levels tend to have higher recurrence rate.

  17. Dehydroepiandrosterone in relation to other adrenal hormones during an acute inflammatory stressful disease state compared with chronic inflammatory disease: role of interleukin-6 and tumour necrosis factor.

    Science.gov (United States)

    Straub, Rainer H; Lehle, Karin; Herfarth, Hans; Weber, Markus; Falk, Werner; Preuner, Jurgen; Scholmerich, Jurgen

    2002-03-01

    Serum levels of dehydroepiandrosterone (DHEA) and DHEA sulphate (DHEAS) are low in chronic inflammatory diseases, although the reasons are unexplained. Furthermore, the behaviour of serum levels of these hormones during an acute inflammatory stressful disease state is not well known. In this study in patients with an acute inflammatory stressful disease state (13 patients undergoing cardiothoracic surgery) and patients with chronic inflammation (61 patients with inflammatory bowel diseases (IBD)) vs. 120 controls, we aimed to investigate adrenal hormone shifts looking at serum levels of DHEA in relation to other adrenal hormones. Furthermore, we tested the predictive role of serum tumour necrosis factor (TNF) and interleukin-6 (IL-6) for a change of serum levels of DHEA in relation to other adrenal hormones. The molar ratio of serum levels of DHEA/androstenedione (ASD) was increased in patients with an acute inflammatory stressful disease state and was decreased in patients with chronic inflammation. The molar ratio of serum levels of DHEAS/DHEA was reduced during an acute inflammatory stressful disease state and was increased in patients with chronic inflammation. A multiple linear regression analysis revealed that elevated serum levels of TNF were associated with a high ratio of serum levels of DHEA/ASD in all groups (for IL-6 in patients with an acute inflammatory stressful disease state only), and, similarly, elevated serum levels of TNF were associated with a high ratio of serum levels of DHEAS/DHEA only in IBD (for IL-6 only in healthy subjects). This study indicates that changes of serum levels of DHEA in relation to serum levels of other adrenal hormones are completely different in patients with an acute inflammatory stressful disease state compared with patients with chronic inflammation. The decrease of serum levels of DHEAS and DHEA is typical for chronic inflammation and TNF and IL-6 play a predictive role for these changes.

  18. Zonulin, a regulator of epithelial and endothelial barrier functions, and its involvement in chronic inflammatory diseases.

    Science.gov (United States)

    Sturgeon, Craig; Fasano, Alessio

    2016-01-01

    Beside digesting nutrients and absorbing solutes and electrolytes, the intestinal epithelium with its barrier function is in charge of a tightly controlled antigen trafficking from the intestinal lumen to the submucosa. This trafficking dictates the delicate balance between tolerance and immune response causing inflammation. Loss of barrier function secondary to upregulation of zonulin, the only known physiological modulator of intercellular tight junctions, leads to uncontrolled influx of dietary and microbial antigens. Additional insights on zonulin mechanism of action and the recent appreciation of the role that altered intestinal permeability can play in the development and progression of chronic inflammatory disorders has increased interest of both basic scientists and clinicians on the potential role of zonulin in the pathogenesis of these diseases. This review focuses on the recent research implicating zonulin as a master regulator of intestinal permeability linked to the development of several chronic inflammatory disorders.

  19. A Proposal for a Study on Treatment Selection and Lifestyle Recommendations in Chronic Inflammatory Diseases

    DEFF Research Database (Denmark)

    Andersen, Vibeke; Holmskov, Uffe; Sørensen, Signe Bek

    2017-01-01

    Chronic inflammatory diseases (CIDs), including Crohn's disease and ulcerative colitis (inflammatory bowel diseases, IBD), rheumatoid arthritis, psoriasis, psoriatic arthritis, spondyloarthritides, hidradenitis suppurativa, and immune-mediated uveitis, are treated with biologics targeting the pro......-inflammatory molecule tumour necrosis factor-α (TNF) (i.e., TNF inhibitors). Approximately one-third of the patients do not respond to the treatment. Genetics and lifestyle may affect the treatment results. The aims of this multidisciplinary collaboration are to identify (1) molecular signatures of prognostic value...... to help tailor treatment decisions to an individual likely to initiate TNF inhibitor therapy, followed by (2) lifestyle factors that support achievement of optimised treatment outcome. This report describes the establishment of a cohort that aims to obtain this information. Clinical data including...

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

    Directory of Open Access Journals (Sweden)

    N. Selve

    1992-01-01

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

  1. Quantitative analysis of the cellular inflammatory response against biofilm bacteria in chronic wounds

    DEFF Research Database (Denmark)

    Fazli, Mustafa; Bjarnsholt, Thomas; Kirketerp-Møller, Klaus

    2011-01-01

    Chronic wounds are an important problem worldwide. These wounds are characterized by a persistent inflammatory stage associated with excessive accumulation and elevated cell activity of neutrophils, suggesting that there must be a persistent stimulus that attracts and recruits neutrophils...... counting on the tissue sections from wounds containing either Pseudomonas aeruginosa or Staphylococcus aureus. The P. aeruginosa-containing wounds had significantly higher numbers of neutrophils accumulated compared with the S. aureus-containing wounds. These results are discussed in relation...

  2. Nonsteroidal anti-inflammatory drug use in patients with chronic kidney disease

    OpenAIRE

    Heleniak, Zbigniew; Cieplińska, Magdalena; Szychliński, Tomasz; Rychter, Dymitr; Jagodzińska, Kalina; Kłos, Alicja; Kuźmiuk, Izabela; Tylicka, Marzena Jakimowicz; Tylicki, Leszek; Rutkowski, Bolesław; Dębska-Ślizień, Alicja

    2016-01-01

    Aims Nonsteroidal anti-inflammatory drugs (NSAIDs) are the cornerstone of pain management. There are no detailed data on NSAIDs use in Poland, especially in patients with chronic kidney disease (CKD). The aim of this study was to evaluate the frequency, circumstances, and causes of NSAIDs use as well as knowledge of their side-effects in patients with CKD. Method This cross-sectional study was conducted in 972 individuals with CKD, enrolled in a written survey originally developed by the auth...

  3. Review article: the potential role of nitric oxide in chronic inflammatory bowel disorders

    DEFF Research Database (Denmark)

    Perner, Anders; Rask-Madsen, J

    1999-01-01

    The aetiology of the chronic inflammatory bowel diseases-ulcerative colitis and Crohn's disease-as well as 'microscopic colitis'-both collagenous (COC) and lymphocytic colitis (LC)-remains unknown. Autoimmune mechanisms, cytokine polymorphism, commensal bacteria, infectious agents and vascular...... impairment have all been proposed as playing important roles in the pathogenesis of this spectrum of diseases. A variety of proinflammatory mediators, including tumour necrosis factor alpha, interleukin-1beta, interferon gamma, leukotriene B4 and platelet activating factor, promote the adherence...

  4. SPECT radiopharmaceuticals for imaging chronic inflammatory diseases in the last decade

    International Nuclear Information System (INIS)

    Anzola, L. K.; Galli, F.; Dierckx, R. A.

    2015-01-01

    In the recent years, many radiopharmaceuticals have been described for the diagnosis of inflammatory chronic diseases. Several peptides, receptor ligands and monoclonal antibodies have been radiolabelled, allowing in-vivo visualization of inflammatory processes at a cellular and molecular level. The labelling of cytokines such as interleukin-1, interleukin-2, interleukin-12 and MCP-1 has facilitated the identification of inflamed synovia in patients with rheumatoid arthritis, active Crohn’s disease, vulnerable atherosclerotic plaques and other targets. The possibility of using monoclonal antibodies against TNF-α, CD2, CD3, CD4 and anti-selectin has not only allowed the localization of inflamed sites but had also a significant impact in helping the selection of patients who can benefit from biological therapies. Regarding radiolabelled peptides, it is important to highlight the increasing use of somatostatin analogues targeting somatostatin receptors in inflammatory diseases, particularly for rheumatoid arthritis, Sjögren syndrome and autoimmune thyroid diseases. In the present review we describe the state of the art of SPECT radiopharmaceuticals to image chronic inflammatory diseases.

  5. Chronic periodontitis prevalence and the inflammatory burden in a sample population from South India.

    Science.gov (United States)

    Balaji, S K; Lavu, Vamsi; Rao, Suresh

    2018-01-01

    Periodontal diseases are among the most prevalent oral diseases in the world. Apart from repercussions in the oral cavity, there is evidence that periodontitis contributes to systemic damage in chronic diseases such as cardiovascular disease, diabetes, and preterm low birth weight. The aims of this study were to estimate the prevalence of chronic periodontitis in a sample urban population (<18 years) in Tamil Nadu and to estimate the inflammatory burden posed by chronic periodontitis by calculating the periodontal inflammatory surface area. This was a population-based study and cross-sectional design. A total of 1000 individuals (<18 years) were selected and screened for their periodontal status, oral hygiene status (OHI), and the periodontal inflamed surface area (PISA) in an outreach center located in Chennai, India. The proportion of individuals with different periodontal states (health, gingivitis, and periodontitis) was determined. A multivariate logistic regression analysis was performed to assess the influence of the individual risk factors such as habits (tobacco use), systemic conditions (diabetes), and oral hygiene maintenance on periodontitis prevalence in the sample population. A high prevalence of periodontal disease was observed in the study population (42.3%). Among the urban participants, age, cigarette smoking, pan chewing, decayed, missing, and filled teeth scores, OHI scores, and PISA scores were found to be significantly associated with periodontitis (P < 0.05). Periodontitis prevalence appears to be high even in areas with adequate access to oral health care and an inflammatory burden risk exists in a definitive manner.

  6. Improvement of hemoglobin levels after a switch from intravenous to subcutaneous administration of immunoglobulin in chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy

    DEFF Research Database (Denmark)

    Markvardsen, Lars Høj; Christiansen, Ingelise; Jakobsen, Johannes

    2016-01-01

    (Hb) and hemolytic variables. RESULTS: Seventeen patients completed the study. At enrollment, the Hb level was 138 ± 12 g/L, haptoglobin level was 1.4 ± 0.5 g/L, reticulocyte count was 58.7 × 10(9) ± 21.3 × 10(9) /L, and bilirubin level was 6.6 ± 2.3 µmol/L. The average of the two blood samples drawn.......9 × 10(9) ± 35.8 × 10(9) to 54.5 × 10(9) ± 16.3 × 10(9) /L (p = 0.02), and bilirubin decreasing from 7.3 ± 2.8 to 5.8 ± 1.8 µmol/L (p = 0.001). CONCLUSION: A switch from IVIG to SCIG was associated with a slight increase of Hb levels and an improvement of laboratory variables related to hemolytic...

  7. A randomised, double-blinded, placebo controlled trial of the effect of subcutaneous immunoglobulin on muscular performance in chronic inflammatory demyelinating polyneuropathy

    DEFF Research Database (Denmark)

    Jakobsen, Johannes Klitgaard; Markvardsen, Lars Høj; Harbo, Thomas

    . Participants were evaluated at four time intervals: - 2 wks, 0, 10 wks, 12 wks. Strength was determined at isokinetic dynamometry from four predetermined and weakened muscle groups. Also, an Overall Disability Sum Score (ODSS), a 40 meter walking test, a nine hole peg test, a Neurological Impairment Score (NIS......), a Medical Research Council (MRC) score and a grip strength test were included. The primary end-point is the change of strength at isokinetic dynamometry in the two study groups. Secondary end-points are the treatment response of SCIG vs IVIG and the variation of the treatment response during SCIG vs IVIG...

  8. A randomized, double-blind, placebo-controlled trial of the effect of subcutaneous immunoglobulin on muscular performance in chronic inflammatory demyelinating polyneuropathy

    DEFF Research Database (Denmark)

    Markvardsen, Lars Høj; Harbo, Thomas; Sindrup, Søren Hein

    before (-2, 0, 10,12 weeks), isokinetic strength performance of four predetermined and weakened muscle groups was performed. Also, the Overall Disability Sum Score (ODSS), 40 meter walking test, nine hole peg test, Neurological Impairment Score (NIS), Medical Research Council (MRC) score and grip...... strength test, standardized electrophysiological recordings from three nerves and plasma IgG levels were obtained. SCIG treatment was well tolerated in all 15 patients for 12 weeks. Six patients complained of mild side effects at the injection site. In the SCIG group there was an increase of isokinetic...

  9. A randomised, double-blinded, placebo-controlled trial of the effect of subcuta-neous immunoglobulin on muscular performance in chronic inflammatory de-myelinating polyneuropathy

    DEFF Research Database (Denmark)

    Harbo, Thomas; Markvardsen, Lars Høj; Sindrup, Søren Hein

    . Participants were evaluated at four time intervals: - 2 weeks, 0, 10 and 12 weeks after treatment with subcutaneous infusions. Muscle strength was determined at isokinetic dynamometry at four predetermined and weakened muscle groups. Moreover, an Overall Disability Sum Score (ODSS), a 40 meter walking test...... at isokinetic dynamometry in the two study groups. Secondary end-points were the treatment response of SCIG vs IVIG and the variation of the treatment response during SCIG vs IVIG. Results: The study ran during the period April 2010 - October 2011. Results will be presented....

  10. Level of inflammatory factors in chronic hemodialysis patients with and without cardiovascular disease

    Directory of Open Access Journals (Sweden)

    Shahram Taheri

    2017-01-01

    Full Text Available Background: Considering the existence of controversies about the predictive value of inflammatory markers for cardiovascular disease (CVD, we aimed to compare the level of high-sensitivity C-reactive protein (hs-CRP and interlukin-6 (IL-6 level in chronic hemodialysis (HD patients with and without CVD. Materials and Methods: In this historical cohort study, HD patients with and without CVD disease were enrolled. The presence of CVD risk factors, level of inflammatory factors including IL-6 and hs-CRP as well as lipid levels, fasting blood sugar, and other biochemical factors were compared in two studied groups. Results: During the study, eighty HD patients with (n = 40 and without (n = 40 CVD were enrolled. Diabetes was more prevalent among HD patients with CVD than those without CVD (P 0.05. Univariate analysis of variance test indicated that there was not any significant relationship between hs-CRP and CVD (P > 0.05. Conclusion: The findings indicated that the level of inflammatory factors including hs-CRP and IL-6 are not significantly different in HD patients with and without CVD. However, for obtaining more definite conclusion in this field and evaluation their predicting role in this field, it is recommended to study other novel inflammatory markers as well as the additive effect of the inflammatory factors with traditional ones in larger sample size and longer follow-up.

  11. Diagnosis and treatment of chronic inflammatory diseases of parodontium; Diagnostika i lechenie khronicheskikh vospalitel`nykh zabolevanij parodonta

    Energy Technology Data Exchange (ETDEWEB)

    Khitrov, V Yu; Zabolotnyj, A I; Khamidullina, S A [Kazanskij Inst. Usovershenstvovaniya Vrachej, Kazan (Russian Federation)

    1995-03-01

    Chronic inflammatory diseases of paradontium have the higher share in the structure of paradontal tissue injuries. The state of bone paradontium is monitored using roentgenographic techniques. The clinical picture of chronic inflammatory diseases consists of the signs of injury of different components of parodontium: gum, periodontitis and alveo bone. The treatment of patients in aimed at eliminating the symptoms of the disease recovery of masticatory ability and prevention of recurrences.

  12. Hepatic inflammatory biomarkers and its link with obesity and chronic diseases.

    Science.gov (United States)

    Pinheiro Volp, Ana Carolina; Santos Silva, Fernanda Cacilda; Bressan, Josefina

    2015-05-01

    The low-grade inflammation and insulin resistance are two events that could be present in varying degrees, on obesity and chronic diseases. The degree of subclinical inflammation can be gauged by measuring the concentrations of some inflammatory biomarkers, including the hepatic origin ones. Some of those biomarkers are sialic acid, α1-antitrypsin and the C-terminal fragment of alpha1-antitrypsin, ceruloplasmin, fibrinogen, haptoglobin, homocystein and plasminogen activator inhibitor-1. To approach the relation between adiposity and hepatic inflammatory markers, and to assess the possible associations between hepatic inflammatory biomarkers and obesity, as well as their capacity of predicting chronic diseases such as type 2 diabetes and atherotrombotic cardiovascular diseases. We used electronic scientific databases to select articles without restricting publication year. The sialic acid predicts the chance increase to become type 2 diabetic independently of BMI. Moreover, the α1-antitripsin, ceruloplasmin, fibrinogen and haptoglobulin biomarkers, seem predict the chance increase to become type 2 diabetic, dependently, of BMI. So, this process could be aggravated by obesity. The concentrations of fibrinogen, homocystein and PAI-1 increase proportionally to insulin resistance, showing its relation with metabolic syndrome (insulin resistance state) and with type 2 diabetes. In relation to cardiovascular diseases, every biomarkers reported in this review seem to increase the risk, becoming useful in add important prognostic. This review integrates the knowledge concerning the possible interactions of inflammatory mediators, in isolation or in conjunction, with obesity and chronic diseases, since these biomarkers play different functions and follow diverse biochemical routes in human body metabolism. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  13. Anti-TNFα therapy for chronic inflammatory disease in kidney transplant recipients: Clinical outcomes.

    Science.gov (United States)

    Garrouste, Cyril; Anglicheau, Dany; Kamar, Nassim; Bachelier, Claire; Rivalan, Joseph; Pereira, Bruno; Caillard, Sophie; Aniort, Julien; Gatault, Philippe; Soubrier, Martin; Sayegh, Johnny; Colosio, Charlotte; Buisson, Anthony; Thervet, Eric; Bouvier, Nicolas; Heng, Anne Elisabeth

    2016-10-01

    Anti-tumor necrosis factor-α (TNFα) therapy has improved the prognosis of many chronic inflammatory diseases. It appears to be well-tolerated by liver-transplant patients. However, their use and their safety in kidney-transplant patients have yet to be determined.In this retrospective study, we identified 16 adult kidney-transplant patients aged 46.5 years (34-51.8) who received anti-TNFα therapy from 7 kidney transplantation centers. The indications for this treatment included: chronic inflammatory bowel disease (n = 8), inflammatory arthritis (n = 5), AA amyloidosis (n = 1), psoriasis (n = 1), and microscopic polyangiitis (n = 1).Anti-TNFα therapies resulted in a clinical response in 13/16 patients (81%). Estimated glomerular filtration rates (MDRD-4) were similar on day 0 and at 24 months (M24) after anti-TNFα treatment had been initiated (41 [12-55] and 40 [21-53] mL/min/1.73 m, respectively). Two allograft losses were observed. The 1st case was due to antibody-mediated rejection (M18), while the 2nd was the result of AA amyloidosis recurrence (M20). There were several complications: 8 patients (50%) developed 23 serious infections (18 bacterial, 4 viral, and 1 fungal) and 4 developed cancer. Five patients died (infection n = 2, cardiac AA amyloidosis n = 1, intraalveolar hemorrhage following microscopic polyangiitis n = 1, and acute respiratory distress syndrome n = 1). On univariate analysis, recipient age associated with death (P = 0.009) and infection development (P = 0.06).Using anti-TNFα therapies, remission can be achieved in chronic inflammatory diseases in kidney-transplant patients. However, concommitant anti-TNFα and immunosuppresive therapies must be used with caution due to the high risk of infection, particularly after the age of 50.

  14. Dietary cholesterol promotes repair of demyelinated lesions in the adult brain.

    Science.gov (United States)

    Berghoff, Stefan A; Gerndt, Nina; Winchenbach, Jan; Stumpf, Sina K; Hosang, Leon; Odoardi, Francesca; Ruhwedel, Torben; Böhler, Carolin; Barrette, Benoit; Stassart, Ruth; Liebetanz, David; Dibaj, Payam; Möbius, Wiebke; Edgar, Julia M; Saher, Gesine

    2017-01-24

    Multiple Sclerosis (MS) is an inflammatory demyelinating disorder in which remyelination failure contributes to persistent disability. Cholesterol is rate-limiting for myelin biogenesis in the developing CNS; however, whether cholesterol insufficiency contributes to remyelination failure in MS, is unclear. Here, we show the relationship between cholesterol, myelination and neurological parameters in mouse models of demyelination and remyelination. In the cuprizone model, acute disease reduces serum cholesterol levels that can be restored by dietary cholesterol. Concomitant with blood-brain barrier impairment, supplemented cholesterol directly supports oligodendrocyte precursor proliferation and differentiation, and restores the balance of growth factors, creating a permissive environment for repair. This leads to attenuated axon damage, enhanced remyelination and improved motor learning. Remarkably, in experimental autoimmune encephalomyelitis, cholesterol supplementation does not exacerbate disease expression. These findings emphasize the safety of dietary cholesterol in inflammatory diseases and point to a previously unrecognized role of cholesterol in promoting repair after demyelinating episodes.

  15. Role of neuroendocrine and neuroimmune mechanisms in chronic inflammatory rheumatic diseases--the 10-year update.

    Science.gov (United States)

    Straub, Rainer H; Bijlsma, Johannes W J; Masi, Alfonse; Cutolo, Maurizio

    2013-12-01

    Neuroendocrine immunology in musculoskeletal diseases is an emerging scientific field. It deals with the aspects of efferent neuronal and neurohormonal bearing on the peripheral immune and musculoskeletal systems. This review aims to add new information that appeared since 2001. The following PubMed search sentence was used to find a total of 15,462 references between 2001 and March 2013: "(rheum* OR SLE OR vasculitis) AND (nerve OR hormone OR neurotransmitter OR neuropeptide OR steroid)." In a continuous process, year by year, this search strategy yielded relevant papers that were screened and collected in a database, which build the platform of this review. The main findings are the anti-inflammatory role of androgens, the loss of androgens (androgen drain), the bimodal role of estrogens (support B cells and inhibit macrophages and T cells), increased conversion of androgens to estrogens in inflammation (androgen drain), disturbances of the gonadal axis, inadequate amount of HPA axis hormones relative to inflammation (disproportion principle), biologics partly improve neuroendocrine axes, anti-corticotropin-releasing hormone therapies improve inflammation (antalarmin), bimodal role of the sympathetic nervous system (proinflammatory early, anti-inflammatory late-most probably due to catecholamine-producing local cells), anti-inflammatory role of alpha melanocyte-stimulating hormone, vasoactive intestinal peptide, and the Vagus nerve via α7 nicotinergic receptors. Circadian rhythms of hypothalamic origin are responsible for circadian rhythms of symptoms (neuroimmune link revealed). Important new pain-sensitizing immunological pathways were found in the last decade. The last decade brought much new information that gave birth to the first therapies of chronic inflammatory diseases on the basis of neuroendocrine immune targets. In addition, a new theory linked evolutionary medicine, neuroendocrine regulation of distribution of energy-rich fuels, and volume

  16. Effects of chronic inflammatory reaction status on the development of complications in patients with chronic renal failure

    International Nuclear Information System (INIS)

    Wang Caili; Wei Feng; Shi Ping; Li Guiling

    2006-01-01

    Objective: To investigate the relationship between changes of serum contents of CRP, IL-6, TNF-α, IL-10 and the development of complications (anemia, malnutrition, atherosclerosis) in patients with chronic renal failure. Methods: Serum IL-6, TNF-α (with RIA) and CRP, IL-10 (with ELISA) levels were determined in 126 patients with chronic renal failure and 36 controls. Blood hemoglobin, albumin, glucose and triglycerides levels were also determined in all these patients. Echocardiography was performed in 95 patients. Results: (1) Serum contents of CRP, IL-6, TNF-α and IL-10 were all significantly higher in the patients than those in the controls (P 6mmol/L, n=83) were significantly higher than those in the corresponding patients without anemia, malnutrition and hyperglycemia ( all P 1.71mmol/L, n=68), the levels were lower than those in patients without high TG (P<0.001 for IL-6, P<0.01 for CRP and IL-10). In patients with aortic arteriosclerosis shown on echocardiography (n=37), levels of the markers were higher than those in patients without arteriosclerosis (n=58) (P<0.001 for IL-10, P<0.001 for CRP and IL-6, P<0.05 for TNF-α). Correlation studies showed that levels of all the four markers were negatively correlated with levels of hemoglobin and albumin, TNF-α levels were correlated with levels of glucose and CRP, IL-6, IL-10 levels were negatively correlated with triglyceride levels. (3) Levels of each of the pro-inflammatory markers (CRP, IL-6, TNF-α) were correlated with levels of the anti-inflammatory cytokine IL-10 (r=0.463, 0.546 and 0.402 respectively). Conclusion: (1) Serum levels of CRP, IL-6, TNF-α and IL-10 were increased in patients with chronic renal failure. (2) Levels of these markers were correlated in some degree with the development of complications (anemia, malnutrition, arteriosclerosis......) in the patients. (3) Levels of pro-inflammatory markers were correlated with levels of anti-inflammatory cytokine IL-10. (authors)

  17. [Cutaneous involvement in chronic inflammatory bowel disease : Crohn's disease and ulcerative colitis].

    Science.gov (United States)

    Richter, L; Rappersberger, K

    2016-12-01

    Over recent decades, both the incidence and prevalence of chronic inflammatory bowel disease have continued to rise in industrialized countries; the disease is frequently associated with extracutaneous involvement and comorbidity. The purpose of this work was to investigate the frequency and specificity of mucocutaneous manifestations in Crohn's disease (CD) and ulcerative colitis (UC). An extensive search in peer-reviewed journals via PubMed was performed; presented is a summary and analysis of various studies and data, including data of patients treated at our department. CD and UC are frequently associated with mucocutaneous symptoms; however, primary/specific disease-associations are exclusively seen in CD patients. These include peri-anal and -stomal fistulas and ulcerations, "metastatic" Crohn's disease as well as oral granulomatous disease. Moreover, in both CD and UC, there occur several other inflammatory skin conditions such as erythema nodosum, pyoderma gangrenosum, hidradenitis suppurativa, chronic oral aphthous disease, Sweet syndrome, pyostomatitis vegetans, and bowel-associated dermatosis-arthritis syndrome. Malnutrition syndromes (zinc and vitamin deficiencies) are only rarely observed. On skin and oral/genital mucous membranes various different inflammatory manifestations may be observed during the course of CD or UC. However, most data about a direct pathogenic relationship of the gastrointestinal and dermatologic disorders are quite heterogeneous or even contradictory. Nevertheless, knowledge of these conditions and their possible association with CD and UC could be crucial for early diagnosis and initiation of an appropriate therapy and thus be essential to prevent secondary tissue damage.

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

    Science.gov (United States)

    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. Mutual interaction of Basophils and T cells in chronic inflammatory diseases

    Directory of Open Access Journals (Sweden)

    Marika eSarfati

    2015-08-01

    Full Text Available 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.

  20. Omega-3 supplementation on inflammatory markers in patients with chronic Chagas cardiomyopathy: a randomized clinical study.

    Science.gov (United States)

    Silva, Paula Simplício da; Mediano, Mauro Felippe Felix; Silva, Gilberto Marcelo Sperandio da; Brito, Patricia Dias de; Cardoso, Claudia Santos de Aguiar; Almeida, Cristiane Fonseca de; Sangenis, Luiz Henrique Conde; Pinheiro, Roberta Olmo; Hasslocher-Moreno, Alejandro Marcel; Brasil, Pedro Emmanuel Alvarenga Americano do; Sousa, Andrea Silvestre de

    2017-06-09

    Several studies have been focusing on the effect of omega-3 polyunsaturated fatty acids on modulation of inflammatory markers in several cardiopathies. Although immunoregulatory dysfunction has been associated to the chronic cardiac involvement in Chagas disease, there is no study examining the effects of omega-3 supplementation in these patients. We investigated the effects of omega-3 PUFAs on markers of inflammation and lipid profile in chronic Chagas cardiomyopathy patients. The present study was a single-center double-blind clinical trial including patients with chronic Chagas cardiomyopathy. Patients were randomly assigned to receive omega-3 PUFAs capsules (1.8g EPA and 1.2g DHA) or placebo (corn oil) during an 8-week period. Cytokines, fasting glucose, lipid, and anthropometric profiles were evaluated. Forty-two patients (23 women and 19 men) were included in the study and there were only two losses to follow-up during the 8-week period. Most of sociodemographic and clinical characteristics were similar between the groups at baseline, except for the cytokines IL-1β, IL-6, IL-8, IL-10, IL-17α, and IFNγ. The omega-3 PUFAs group demonstrated greater improvements in serum triglycerides (-21.1 vs. -4.1; p = 0.05) and IL-10 levels (-10.6 vs. -35.7; p = 0.01) in comparison to controls after 8 weeks of intervention. No further differences were observed between groups. Omega-3 PUFAs supplementation may favorably affect lipid and inflammatory profile in chronic Chagas cardiomyopathy patients, demonstrated by a decrease in triglycerides and improvements on IL-10 concentration. Further studies examining the clinical effects of omega-3 fatty acids supplementation in chronic Chagas cardiomyopathy are necessary. NCT01863576.

  1. IL-35, a hallmark of immune-regulation in cancer progression, chronic infections and inflammatory diseases.

    Science.gov (United States)

    Teymouri, Manouchehr; Pirro, Matteo; Fallarino, Francesca; Gargaro, Marco; Sahebkar, Amirhosein

    2018-03-25

    Cytokine members of the IL-12 family have attracted enormous attention in the last few years, with IL-35 being the one of the most attractive-suppressive cytokine. IL-35 is an important mediator of regulatory T cell function. Regulatory T cells play key roles in restoring immune homeostasis after facing challenges such as infection by specific pathogens. Moreover, a crucial role for regulatory T cell populations has been demonstrated in several physiological processes, including establishment of fetal-maternal tolerance, maintenance of self-tolerance and prevention of autoimmune diseases. However, a deleterious involvement of immune regulatory T cells has been documented in specific inhibition of immune responses against tumor cells, promotion of chronic infections and establishment of chronic inflammatory disorders. In this review, we attempt to shed light on the concept of immune-homoeostasis on the aforementioned issues, taking IL-35 as the hallmark of regulatory responses. The dilemma between immune-mediated cancer treatment and inflammation is discussed. Histopathological indications of chronic vs. acute infections are elaborated. Moreover, the evidence that IL-35 requires additional immune-regulatory cytokines, such as IL-10 and TGF-β, to induce effective and maximal anti-inflammatory effects suggest that immune-regulation requires multi-factorial analysis of many immune playmakers rather than a specific immune target. © 2018 UICC.

  2. Inflammatory C-reactive protein and cytokine levels in asymptomatic people with chronic spinal cord injury.

    Science.gov (United States)

    Frost, Frederick; Roach, Mary Jo; Kushner, Irving; Schreiber, Peter

    2005-02-01

    To determine the relation between serologic markers of information and clinical characteristics of people with chronic spinal cord injury (SCI). Cross-sectional study. Academic medical center SCI outpatient clinic. Convenience sample of 37 men with chronic SCI and 10 healthy control subjects. Not applicable. Serum levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and C-reactive protein (CRP). The following results achieved statistical significance at P less than .05. Asymptomatic chronic SCI patients differed from referent controls with respect to serum CRP levels but not IL-6 or TNF-alpha. In SCI patients, higher levels of CRP correlated negatively with hemoglobin and albumin levels. A longer time since injury correlated with lower TNF-alpha values, whereas higher TNF-alpha levels correlated with higher serum albumin. Pressure ulcers and indwelling urinary catheters were associated with higher mean levels of CRP but not of the cytokines TNF-alpha and IL-6. Intermittent urinary catheterization was associated with lower levels of CRP when compared with other methods of bladder management. Asymptomatic people with long-term SCI, especially those with indwelling urinary catheters, showed serologic evidence of a systemic inflammatory state. There was no evidence of an elevation in proinflammatory cytokines. Detection of an ongoing systemic inflammatory response in apparently healthy people with indwelling urinary catheters and small skin ulcers further supports the aggressive pursuit of catheter-free voiding options and pressure ulcer healing.

  3. Chronic Disseminated Candidiasis Complicated by Immune Reconstitution Inflammatory Syndrome in Child with Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Olga Zając-Spychała

    2016-01-01

    Full Text Available Hepatosplenic candidiasis also known as chronic disseminated candidiasis is a rare manifestation of invasive fungal infection typically observed in patients with acute leukemia in prolonged, deep neutropenia. Immune reconstitution inflammatory syndrome (IRIS is an inflammatory disorder triggered by rapid resolution of neutropenia. Diagnosis and treatment of IRIS are still challenging due to a variety of clinical symptoms, lack of certain diagnostic criteria, and no standards of treatment. The diagnosis of IRIS is even more difficult in patients with hematological malignancies complicated by “probable” invasive fungal infection, when fungal pathogen is still uncertain. We report a case of probable hepatic candidiasis in 4-year-old boy with acute lymphoblastic leukemia. Despite proper antifungal therapy, there was no clinical and radiological improvement, so diagnosis of Candida-related IRIS was made and corticosteroid therapy was added to antifungal treatment achieving prompt resolution of infection symptoms.

  4. Study of inflammatory markers and BODE index in chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Priti Lokesh Meshram

    2018-01-01

    Full Text Available Introduction: Chronic obstructive pulmonary disease (COPD is a common preventable and treatable disease characterized by progressive airflow limitation and associated with enhanced chronic inflammatory response of the airways to a variety of noxious stimuli. The current concept of COPD, however, extends beyond the respiratory system to include a variety of extrapulmonary manifestations which includes raised inflammatory markers. Methods: This was a single, center observational open-labeled case–controlled study which included fifty patients of diagnosed COPD and 50 age- and gender-matched controls. All patients were evaluated by detailed history taking, pulmonary function test, 6-min walk test, and calculation of BODE scores. Levels of serum inflammatory markers such as cortisol, tumor necrosis factor alpha, interleukin-6 (IL-6, lactate dehydrogenase, and C-reactive protein were estimated using standard quality equipments. Observations: Majority of the patients in the study and control groups were males and were aged above 40 years. Thirty-eight of the fifty COPD patients had BODE scores of more than 3. All the studied inflammatory markers were significantly higher in the COPD group as compared to the control group. Of all the studied markers, only IL-6 showed a significant correlation with BODE index, i.e., higher IL-6 values were associated with higher BODE scores. No correlation was seen between the other markers and BODE scores. Conclusions: Our data suggest that IL-6 is a biomarker that correlates with BODE score. IL-6 as a target for therapy in COPD needs to be further studied. Follow-up studies are needed to validate findings.

  5. Malignant transformation of oral lichen planus by a chronic inflammatory process. Use of topical corticosteroids to prevent this progression?

    Science.gov (United States)

    Otero-Rey, Eva Maria; Suarez-Alen, Fatima; Peñamaria-Mallon, Manuel; Lopez-Lopez, Jose; Blanco-Carrion, Andres

    2014-11-01

    Oral lichen planus is a potentially malignant disorder with a capacity, although low, for malignant transformation. Of all the factors related to the process of malignant transformation, it is believed that the chronic inflammatory process plays a key role in the development of oral cancer. This inflammatory process is capable of providing a microenvironment based on different inflammatory cells and molecules that affect cellular growth, proliferation and differentiation. The objectives of our study are: to review the available evidence about the possible relationship between the chronic inflammatory process present in oral lichen planus and its malignant transformation, to discuss the potential therapeutic implications derived from this relationship and to study the role that topical corticosteroids play in the control of oral lichen planus inflammation and its possible progression to malignant transformation. The maintenance of a minimum dose of topical corticosteroids could prevent the inflammatory progression of oral lichen planus to oral cancer.

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

    Directory of Open Access Journals (Sweden)

    Shahedi K

    2013-10-01

    Full Text Available Kamyar Shahedi,1,2 Ramy Magdy Hanna,1,2 Oleg Melamed,1,2 James Wilson2,31Department of Medicine Olive-View UCLA Medical Center, Sylmar, CA, 2David Geffen School of Medicine at UCLA, Los Angeles, CA, 3UCLA Medical Center-UCLA Stone Center, Los Angeles, CA, USAAbstract: 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.Keywords: ANCA-associated vasculitis, Wegener’s syndrome, pauci-immune glomerulonephritis, Salmonella arizonae, inflammatory bowel disease

  7. Chronic periodontitis prevalence and the inflammatory burden in a sample population from South India

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    S K Balaji

    2018-01-01

    Full Text Available Context: Periodontal diseases are among the most prevalent oral diseases in the world. Apart from repercussions in the oral cavity, there is evidence that periodontitis contributes to systemic damage in chronic diseases such as cardiovascular disease, diabetes, and preterm low birth weight. Aims: The aims of this study were to estimate the prevalence of chronic periodontitis in a sample urban population (<18 years in Tamil Nadu and to estimate the inflammatory burden posed by chronic periodontitis by calculating the periodontal inflammatory surface area. Settings and Design: This was a population-based study and cross-sectional design. Subjects and Methods: A total of 1000 individuals (<18 years were selected and screened for their periodontal status, oral hygiene status (OHI, and the periodontal inflamed surface area (PISA in an outreach center located in Chennai, India. Statistical Analysis Used: The proportion of individuals with different periodontal states (health, gingivitis, and periodontitis was determined. A multivariate logistic regression analysis was performed to assess the influence of the individual risk factors such as habits (tobacco use, systemic conditions (diabetes, and oral hygiene maintenance on periodontitis prevalence in the sample population. Results: A high prevalence of periodontal disease was observed in the study population (42.3%. Among the urban participants, age, cigarette smoking, pan chewing, decayed, missing, and filled teeth scores, OHI scores, and PISA scores were found to be significantly associated with periodontitis (P < 0.05. Conclusions: Periodontitis prevalence appears to be high even in areas with adequate access to oral health care and an inflammatory burden risk exists in a definitive manner.

  8. Chronic inflammatory gingival enlargement associated with orthodontic therapy--a case report.

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    Jadhav, Tanya; Bhat, K Mahalinga; Bhat, G Subraya; Varghese, Jothi M

    2013-02-01

    Gingival enlargement, also synonymous with the terms gingival hyperplasia or hypertrophy, is defined as an abnormal overgrowth of gingival tissues. A case of a 19-year-old male presenting with maxillary and mandibular chronic inflammatory gingival enlargement associated with prolonged orthodontic therapy is reported here. Surgical therapy was carried out to provide a good aesthetic outcome. No recurrence was reported at the end of 1 year. The importance of patient motivation and compliance during and after therapy as a critical factor in the success of treatment has also been highlighted through this case report.

  9. Ferrokinetic Parameters and Regulation of Iron Metabolism in Patients with Chronic Inflammatory Bowel Diseases

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    T.Y. Boiko

    2014-11-01

    Full Text Available Article presents parameters of iron metabolism and cytokines (IL-6 and TNF-α in patients with chronic inflammatory bowel diseases (CIBD. The material for the study was the blood of 69 patients with CIBD and anemia and 26 — without anemia. We have studied the features of main ferrokinetic parameters — iron, total iron-binding capacity of serum, transferrin saturation, ferritin, transferrin receptor, erythropoietin, hepcidin depending on hemoglobin level and the type of anemia. The relationship of iron metabolism disorders with the level of proinflammatory cytokines (IL-6 and TNF-α is shown.

  10. Granulomatous lobular mastitis: a rare chronic inflammatory disease of the breast which can mimic breast carcinoma.

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    Verfaillie, G; Breucq, C; Sacre, R; Bourgain, C; Lamote, J

    2006-01-01

    Granulomatous lobular mastitis is a rare chronic inflammatory disease of the breast. The differential diagnosis with malign breast disease is often not easy. In most cases a surgical biopsy is needed for correct diagnosis. Idiopathic granulomatous mastitis is an exclusion diagnosis, based on the demonstration of a characteristic histological pattern, combined with the exclusion of other possible causes of granulomatous breast lesions. There is still no generally accepted optimal treatment. If surgery forms part of the treatment, a conservative approach seems to be adequate in most cases. Another option is a long-term steroid treatment. It is mandatory to exclude infectious causes of granulomatous mastitis before corticoid therapy is started.

  11. A novel collaborative representation and SCAD based classification method for fibrosis and inflammatory activity analysis of chronic hepatitis C

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    Cai, Jiaxin; Chen, Tingting; Li, Yan; Zhu, Nenghui; Qiu, Xuan

    2018-03-01

    In order to analysis the fibrosis stage and inflammatory activity grade of chronic hepatitis C, a novel classification method based on collaborative representation (CR) with smoothly clipped absolute deviation penalty (SCAD) penalty term, called CR-SCAD classifier, is proposed for pattern recognition. After that, an auto-grading system based on CR-SCAD classifier is introduced for the prediction of fibrosis stage and inflammatory activity grade of chronic hepatitis C. The proposed method has been tested on 123 clinical cases of chronic hepatitis C based on serological indexes. Experimental results show that the performance of the proposed method outperforms the state-of-the-art baselines for the classification of fibrosis stage and inflammatory activity grade of chronic hepatitis C.

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

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    Kalimuthu Senthilkumar

    2013-01-01

    Full Text Available 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.

  13. Anti-inflammatory and antioxidant effects of umbelliferone in chronic alcohol-fed rats

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    Sim, Mi-Ok; Lee, Hae-In; Ham, Ju Ri; Seo, Kwon-Il; Kim, Myung-Joo

    2015-01-01

    BACKGROUND/OBJECTIVES Inflammation is associated with various types of acute and chronic alcohol liver diseases. In this study, we examined whether umbelliferone (7-hydroxycoumarin, UF) ameliorates chronic alcohol-induced liver damage by modulating inflammatory response and the antioxidant system. METHODS Rats were fed a Liber-Decarli liquid diet containing 5% alcohol with or without UF (0.05 g/L) for 8 weeks, while normal rats received an isocaloric carbohydrate liquid diet. RESULTS Chronic alcohol intake significantly increased serum tumor necrosis factor-α (TNF-α) and interleukin 6 levels and decreased interleukin 10 level; however, UF supplementation reversed the cytokines related to liver damage. UF significantly suppressed hepatic lipopolysaccharide binding protein, toll-like receptor 4 (TLR4), nuclear factor kappa B, and TNF-α gene expression increases in response to chronic alcohol intake. Masson's trichrome staining revealed that UF improved mild hepatic fibrosis caused by alcohol, and UF also significantly increased the mRNA expressions and activities of superoxide dismutase and catalase in liver, and thus, decreased lipid peroxide and mitochondrial hydrogen peroxide levels. CONCLUSIONS The findings of this study indicate that UF protects against alcohol-induced liver damage by inhibiting the TLR4 signaling pathway and activating the antioxidant system. PMID:26244074

  14. Demyelinating diseases and potential repair strategies

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    Radtke, C.; Spies, M.; Sasaki, M.; Vogt, PM; Kocsis, J. D.

    2009-01-01

    Demyelination is associated with a number of neurological disorders including multiple sclerosis (MS), spinal cord injury and nerve compression. MS lesions often show axon loss and therefore reparative therapeutic goals include remyelination and neuroprotection of vulnerable axons. Experimental cellular transplantation has proven successful in a number of demyelination and injury models to remyelinate and improve functional outcome. Here we discuss the remyelination and neuroprotective potential of several myelin-forming cells types and their behavior in different demyelination and injury models. Better understanding of these models and current cell-based strategies for remyelination and neuroprotection offer exciting opportunities to develop strategies for clinical studies. PMID:17408905

  15. Drug Hypersensitivity and Anaphylaxis in Cancer and Chronic Inflammatory Diseases: The Role of Desensitizations

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    Mariana Castells

    2017-11-01

    Full Text Available Drug allergy is a rising problem in the twenty-first century which affects all populations and races, children, and adults, and for which the recognition, diagnosis, management, and treatment is still not well standardized. Classical and new chemotherapy drugs, monoclonal antibodies (MoAbs, and small molecules to treat cancer and chronic inflammatory diseases are aimed at improving quality of life and life expectancy of patients, but an increasing number of reactions including anaphylaxis precludes their use in targeted populations. Women are more affected by drug allergy and up to 27% of women with ovarian and breast cancer develop carboplatin allergy after multiple cycles of treatment. Carriers of BRCA genes develop drug allergy after fewer exposures and can present with severe reactions, including anaphylaxis. Atopic patients are at increased risk for chemotherapy and MoAbs drug allergy and the current patterns of treatment with recurrent and intermittent drug exposures may favor the development of drug allergies. To overcome drug allergy, desensitization has been developed, a novel approach which provides a unique opportunity to protect against anaphylaxis and to improve clinical outcomes. There is evidence that inhibitory mechanisms blocking IgE/antigen mast cell activation are active during desensitization, enhancing safety. Whether desensitization modulates drug allergic and anaphylactic responses facilitating tolerance is currently being investigated. This review provides insight into the current knowledge of drug allergy and anaphylaxis to cancer and chronic inflammatory diseases drugs, the mechanisms of drug desensitization and its applications to personalized medicine.

  16. Serum leveis of inflammatory markers in type 2 diabetes patients with chronic periodontitis

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    Priscila Larcher LONGO

    2014-04-01

    Full Text Available Diabetes has been associated with periodontitis, but the mechanisms through which periodontal diseases affect the metabolic control remain unclear. Objective: This study aimed to evaluate serum leveis of inflammatory markers, IL-8, IL-6 and monocyte chemoattractant protein 1 (MCP-1, in type 2 diabetic patients in the presence of chronic periodontitis. Material and Methods: Forty two individuals were enrolled in this study and assigned to one of five groups: diabetes mellitus with inadequate glycemic control and periodontitis (DMI+P, n = 10, diabetes mellitus with adequate glycemic control and periodontitis (DMA+P, n = 10, diabetes mellitus without periodontitis (DM, n = 10, periodontitis without diabetes (P, n=6, and neither diabetes nor periodontitis (H, n = 6. Periodontal clinical examination included visible plaque index (PL, gingival bleeding index (GB, probing depth (PD, attachment level (AL and bleeding on probing (BP. Glycemic control was evaluated by serum concentration of glycated hemoglobin (HbAlc. Inflammatory serum markers IL-8, IL-6 and (MCP-1 were measured by ELISA. Results: DMI+P and DMA+P groups presented higher PD (p=0.025 and AL (p=0.003 values when compared to the P group. There were no significant differences among groups for IL-6, IL-8 and MCP-1 serum levels. Conclusions: Although periodontitis was more severe in diabetic patients, the serum levels of the investigated inflammatory markers did not differ among the groups.

  17. The Effect of Resistance Exercise on Inflammatory and Myogenic Markers in Patients with Chronic Kidney Disease

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    Emma L. Watson

    2017-07-01

    Full Text Available Background: Muscle wasting is a common complication of Chronic Kidney Disease (CKD and is clinically important given its strong association with morbidity and mortality in many other chronic conditions. Exercise provides physiological benefits for CKD patients, however the molecular response to exercise remains to be fully determined. We investigated the inflammatory and molecular response to resistance exercise before and after training in these patients.Methods: This is a secondary analysis of a randomized trial that investigated the effect of 8 week progressive resistance training on muscle mass and strength compared to non-exercising controls. A sub-set of the cohort consented to vastus lateralis skeletal muscle biopsies (n = 10 exercise, n = 7 control in which the inflammatory response (IL-6, IL-15, MCP-1 TNF-α, myogenic (MyoD, myogenin, myostatin, anabolic (P-Akt, P-eEf2 and catabolic events (MuRF-1, MAFbx, 14 kDa, ubiquitin conjugates and overall levels of oxidative stress have been studied.Results: A large inflammatory response to unaccustomed exercise was seen with IL-6, MCP-1, and TNF-α all significantly elevated from baseline by 53-fold (P < 0.001, 25-fold (P < 0.001, and 4-fold (P < 0.001, respectively. This response was reduced following training with IL-6, MCP-1, and TNF-α elevated non-significantly by 2-fold (P = 0.46, 2.4-fold (P = 0.19, and 2.5-fold (P = 0.06, respectively. In the untrained condition, an acute bout of resistance exercise did not result in increased phosphorylation of Akt (P = 0.84, but this was restored following training (P = 0.01. Neither unaccustomed nor accustomed exercise resulted in a change in myogenin or MyoD mRNA expression (P = 0.88, P = 0.90, respectively. There was no evidence that resistance exercise training created a prolonged oxidative stress response within the muscle, or increased catabolism.Conclusions: Unaccustomed exercise creates a large inflammatory response within the muscle, which is

  18. Original paper Influence of biologic therapy on growth in children with chronic inflammatory connective tissue diseases

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    Joanna Świdrowska

    2015-04-01

    Full Text Available 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--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

  19. Experimental Demyelination and Axonal Loss Are Reduced in MicroRNA-146a Deficient Mice.

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    Martin, Nellie A; Molnar, Viktor; Szilagyi, Gabor T; Elkjaer, Maria L; Nawrocki, Arkadiusz; Okarmus, Justyna; Wlodarczyk, Agnieszka; Thygesen, Eva K; Palkovits, Miklos; Gallyas, Ferenc; Larsen, Martin R; Lassmann, Hans; Benedikz, Eirikur; Owens, Trevor; Svenningsen, Asa F; Illes, Zsolt

    2018-01-01

    reduced in the demyelinating corpus callosum of the KO mice. During demyelination, absence of miR-146a reduced inflammatory responses, demyelination, axonal loss, the number of infiltrating macrophages, and increased the number of myelinating oligodendrocytes. The number of OPCs was slightly higher in the WT mice during remyelination, indicating a complex role of miR-146a during in vivo de- and remyelination.

  20. Experimental Demyelination and Axonal Loss Are Reduced in MicroRNA-146a Deficient Mice

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    Nellie A. Martin

    2018-03-01

    Iba1+ macrophages/microglia was reduced in the demyelinating corpus callosum of the KO mice.ConclusionDuring demyelination, absence of miR-146a reduced inflammatory responses, demyelination, axonal loss, the number of infiltrating macrophages, and increased the number of myelinating oligodendrocytes. The number of OPCs was slightly higher in the WT mice during remyelination, indicating a complex role of miR-146a during in vivo de- and remyelination.

  1. A rare presentation of atypical demyelination: tumefactive multiple sclerosis causing Gerstmann’s syndrome

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    2014-01-01

    Background Tumefactive demyelinating lesions are a rare manifestation of multiple sclerosis (MS). Differential diagnosis of such space occupying lesions may not be straightforward and sometimes necessitate brain biopsy. Impaired cognition is the second most common clinical manifestation of tumefactive MS; however complex cognitive syndromes are unusual. Case presentation We report the case of a 30 year old woman who presented with Gerstmann’s syndrome. MRI revealed a large heterogeneous contrast enhancing lesion in the left cerebral hemisphere. Intravenous corticosteroids did not stop disease progression. A tumour or cerebral lymphoma was suspected, however brain biopsy confirmed inflammatory demyelination. Following diagnosis of tumefactive MS treatment with natalizumab effectively suppressed disease activity. Conclusions The case highlights the need for clinicians, radiologists and surgeons to appreciate the heterogeneous presentation of tumefactive MS. Early brain biopsy facilitates rapid diagnosis and management. Treatment with natalizumab may be useful in cases of tumefactive demyelination where additional evidence supports a diagnosis of relapsing MS. PMID:24694183

  2. Genetic and metabolic signals during acute enteric bacterial infection alter the microbiota and drive progression to chronic inflammatory disease

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    Kamdar, Karishma; Khakpour, Samira; Chen, Jingyu; Leone, Vanessa; Brulc, Jennifer; Mangatu, Thomas; Antonopoulos, Dionysios A.; Chang, Eugene B; Kahn, Stacy A.; Kirschner, Barbara S; Young, Glenn; DePaolo, R. William

    2016-01-13

    Chronic inflammatory disorders are thought to arise due to an interplay between predisposing host genetics and environmental factors. For example, the onset of inflammatory bowel disease is associated with enteric proteobacterial infection, yet the mechanistic basis for this association is unclear. We have shown previously that genetic defiency in TLR1 promotes acute enteric infection by the proteobacteria Yersinia enterocolitica. Examining that model further, we uncovered an altered cellular immune response that promotes the recruitment of neutrophils which in turn increases metabolism of the respiratory electron acceptor tetrathionate by Yersinia. These events drive permanent alterations in anti-commensal immunity, microbiota composition, and chronic inflammation, which persist long after Yersinia clearence. Deletion of the bacterial genes involved in tetrathionate respiration or treatment using targeted probiotics could prevent microbiota alterations and inflammation. Thus, acute infection can drive long term immune and microbiota alterations leading to chronic inflammatory disease in genetically predisposed individuals.

  3. A Mechanism of Virus-Induced Demyelination

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    Jayasri Das Sarma

    2010-01-01

    Full Text Available Myelin forms an insulating sheath surrounding axons in the central and peripheral nervous systems and is essential for rapid propagation of neuronal action potentials. Demyelination is an acquired disorder in which normally formed myelin degenerates, exposing axons to the extracellular environment. The result is dysfunction of normal neuron-to-neuron communication and in many cases, varying degrees of axonal degeneration. Numerous central nervous system demyelinating disorders exist, including multiple sclerosis. Although demyelination is the major manifestation of most of the demyelinating diseases, recent studies have clearly documented concomitant axonal loss to varying degrees resulting in long-term disability. Axonal injury may occur secondary to myelin damage (outside-in model or myelin damage may occur secondary to axonal injury (inside-out model. Viral induced demyelination models, has provided unique imminent into the cellular mechanisms of myelin destruction. They illustrate mechanisms of viral persistence, including latent infections, virus reactivation and viral-induced tissue damage. These studies have also provided excellent paradigms to study the interactions between the immune system and the central nervous system (CNS. In this review we will discuss potential cellular and molecular mechanism of central nervous system axonal loss and demyelination in a viral induced mouse model of multiple sclerosis.

  4. Oxidative stress and proinflammatory cytokines contribute to demyelination and axonal damage in a cerebellar culture model of neuroinflammation.

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    di Penta, Alessandra; Moreno, Beatriz; Reix, Stephanie; Fernandez-Diez, Begoña; Villanueva, Maite; Errea, Oihana; Escala, Nagore; Vandenbroeck, Koen; Comella, Joan X; Villoslada, Pablo

    2013-01-01

    Demyelination and axonal damage are critical processes in the pathogenesis of multiple sclerosis (MS). Oxidative stress and pro-inflammatory cytokines elicited by inflammation mediates tissue damage. To monitor the demyelination and axonal injury associated with microglia activation we employed a model using cerebellar organotypic cultures stimulated with lipopolysaccharide (LPS). Microglia activated by LPS released pro-inflammatory cytokines (IL-1β, IL-6 and TNFα), and increased the expression of inducible nitric oxide synthase (iNOS) and production of reactive oxygen species (ROS). This activation was associated with demyelination and axonal damage in cerebellar cultures. Axonal damage, as revealed by the presence of non-phosphorylated neurofilaments, mitochondrial accumulation in axonal spheroids, and axonal transection, was associated with stronger iNOS expression and concomitant increases in ROS. Moreover, we analyzed the contribution of pro-inflammatory cytokines and oxidative stress in demyelination and axonal degeneration using the iNOS inhibitor ethyl pyruvate, a free-scavenger and xanthine oxidase inhibitor allopurinol, as well as via blockage of pro-inflammatory cytokines using a Fc-TNFR1 construct. We found that blocking microglia activation with ethyl pyruvate or allopurinol significantly decreased axonal damage, and to a lesser extent, demyelination. Blocking TNFα significantly decreased demyelination but did not prevented axonal damage. Moreover, the most common therapy for MS, interferon-beta, was used as an example of an immunomodulator compound that can be tested in this model. In vitro, interferon-beta treatment decreased oxidative stress (iNOS and ROS levels) and the release of pro-inflammatory cytokines after LPS stimulation, reducing axonal damage. The model of neuroinflammation using cerebellar culture stimulated with endotoxin mimicked myelin and axonal damage mediated by the combination of oxidative stress and pro-inflammatory cytokines

  5. Oxidative Stress and Proinflammatory Cytokines Contribute to Demyelination and Axonal Damage in a Cerebellar Culture Model of Neuroinflammation

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    di Penta, Alessandra; Moreno, Beatriz; Reix, Stephanie; Fernandez-Diez, Begoña; Villanueva, Maite; Errea, Oihana; Escala, Nagore; Vandenbroeck, Koen; Comella, Joan X.; Villoslada, Pablo

    2013-01-01

    Background Demyelination and axonal damage are critical processes in the pathogenesis of multiple sclerosis (MS). Oxidative stress and pro-inflammatory cytokines elicited by inflammation mediates tissue damage. Methods/Principal Findings To monitor the demyelination and axonal injury associated with microglia activation we employed a model using cerebellar organotypic cultures stimulated with lipopolysaccharide (LPS). Microglia activated by LPS released pro-inflammatory cytokines (IL-1β, IL-6 and TNFα), and increased the expression of inducible nitric oxide synthase (iNOS) and production of reactive oxygen species (ROS). This activation was associated with demyelination and axonal damage in cerebellar cultures. Axonal damage, as revealed by the presence of non-phosphorylated neurofilaments, mitochondrial accumulation in axonal spheroids, and axonal transection, was associated with stronger iNOS expression and concomitant increases in ROS. Moreover, we analyzed the contribution of pro-inflammatory cytokines and oxidative stress in demyelination and axonal degeneration using the iNOS inhibitor ethyl pyruvate, a free-scavenger and xanthine oxidase inhibitor allopurinol, as well as via blockage of pro-inflammatory cytokines using a Fc-TNFR1 construct. We found that blocking microglia activation with ethyl pyruvate or allopurinol significantly decreased axonal damage, and to a lesser extent, demyelination. Blocking TNFα significantly decreased demyelination but did not prevented axonal damage. Moreover, the most common therapy for MS, interferon-beta, was used as an example of an immunomodulator compound that can be tested in this model. In vitro, interferon-beta treatment decreased oxidative stress (iNOS and ROS levels) and the release of pro-inflammatory cytokines after LPS stimulation, reducing axonal damage. Conclusion The model of neuroinflammation using cerebellar culture stimulated with endotoxin mimicked myelin and axonal damage mediated by the combination of

  6. Inhibition of GABA A receptor improved special memory impairment in the local model of demyelination in rat hippocampus.

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    Mousavi Majd, Alireza; Ebrahim Tabar, Forough; Afghani, Arghavan; Ashrafpour, Sahand; Dehghan, Samaneh; Gol, Mohammad; Ashrafpour, Manouchehr; Pourabdolhossein, Fereshteh

    2018-01-15

    Cognitive impairment and memory deficit are common features in multiple Sclerosis patients. The mechanism of memory impairment in MS is unknown, but neuroimaging studies suggest that hippocampal demyelination is involved. Here, we investigate the role of GABA A receptor on spatial memory in the local model of hippocampal demyelination. Demyelination was induced in male Wistar rats by bilaterally injection of lysophosphatidylcholine (LPC) 1% into the CA1 region of the hippocampus. The treatment groups were received daily intraventricular injection of bicuculline (0.025, 0.05μg/2μl/animal) or muscimol (0.1, 0.2μg/2μl/animal) 5days after LPC injection. Morris Water Maze was used to evaluate learning and memory in rats. We used Luxol fast blue staining and qPCR to assess demyelination extention and MBP expression level respectively. Immunohistochemistry (IHC) for CD45 and H&E staining were performed to assess inflammatory cells infiltration. Behavioral study revealed that LPC injection in the hippocampus impaired learning and memory function. Animals treated with both doses of bicuculline improved spatial learning and memory function; however, muscimol treatment had no effect. Histological and MBP expression studies confirmed that demylination in LPC group was maximal. Bicuculline treatment significantly reduced demyelination extension and increased the level of MBP expression. H&E and IHC results showed that bicuculline reduced inflammatory cell infiltration in the lesion site. Bicuculline improved learning and memory and decreased demyelination extention in the LPC-induced hippocampal demyelination model. We conclude that disruption of GABAergic homeostasis in hippocampal demyelination context may be involved in memory impairment with the implications for both pathophysiology and therapy. Copyright © 2017. Published by Elsevier B.V.

  7. Extra pontine osmotic demyelination syndrome.

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    Zunga, Pervaiz M; Farooq, Omar; Dar, Mohd I; Dar, Ishrat H; Rashid, Samia; Rather, Abdul Q; Basu, Javid A; Ashraf, Mohammed; Bhat, Jahangeer A

    2015-01-01

    The osmotic demyelination syndrome (ODS) has been identified as a complication of the rapid correction of hyponatremia for decades. However, in recent years, a variety of other medical conditions have been associated with the development of ODS, independent of changes in serum sodium which cause a rapid changes in osmolality of the interstitial (extracellular) compartment of the brain leading to dehydration of energy-depleted cells with subsequent axonal damage that occurs in characteristic areas. Slow correction of the serum sodium concentration and additional administration of corticosteroids seems to be a major prevention step in ODS patients. In the current report we aimed to share a rare case which we observed in our hospital. A 65 year old female admitted as altered sensorium with history of vomiting, diarrhea was managed with intravenous fluids for 2 days at a peripheral health centre. Patient was referred to our centre with encephalopathy, evaluated and found to have hyponatremia and hypokalemia rest of biochemical parameters and septic profile were normal. Patient's electrolyte disturbances were managed as per guidelines but encephalopathy persisted. Supportive treatment was continued and patient was discharged after 2 wks of stay in hospital after gaining full sensorium and neurological functions.

  8. Creatine Enhances Mitochondrial-Mediated Oligodendrocyte Survival After Demyelinating Injury.

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    Chamberlain, Kelly A; Chapey, Kristen S; Nanescu, Sonia E; Huang, Jeffrey K

    2017-02-08

    Chronic oligodendrocyte loss, which occurs in the demyelinating disorder multiple sclerosis (MS), contributes to axonal dysfunction and neurodegeneration. Current therapies are able to reduce MS severity, but do not prevent transition into the progressive phase of the disease, which is characterized by chronic neurodegeneration. Therefore, pharmacological compounds that promote oligodendrocyte survival could be beneficial for neuroprotection in MS. Here, we investigated the role of creatine, an organic acid involved in adenosine triphosphate (ATP) buffering, in oligodendrocyte function. We found that creatine increased mitochondrial ATP production directly in oligodendrocyte lineage cell cultures and exerted robust protection on oligodendrocytes by preventing cell death in both naive and lipopolysaccharide-treated mixed glia. Moreover, lysolecithin-mediated demyelination in mice deficient in the creatine-synthesizing enzyme guanidinoacetate-methyltransferase ( Gamt ) did not affect oligodendrocyte precursor cell recruitment, but resulted in exacerbated apoptosis of regenerated oligodendrocytes in central nervous system (CNS) lesions. Remarkably, creatine administration into Gamt -deficient and wild-type mice with demyelinating injury reduced oligodendrocyte apoptosis, thereby increasing oligodendrocyte density and myelin basic protein staining in CNS lesions. We found that creatine did not affect the recruitment of macrophages/microglia into lesions, suggesting that creatine affects oligodendrocyte survival independently of inflammation. Together, our results demonstrate a novel function for creatine in promoting oligodendrocyte viability during CNS remyelination. SIGNIFICANCE STATEMENT We report that creatine enhances oligodendrocyte mitochondrial function and protects against caspase-dependent oligodendrocyte apoptosis during CNS remyelination. This work has important implications for the development of therapeutic targets for diseases characterized by

  9. Crosstalk between type II NKT cells and T cells leads to spontaneous chronic inflammatory liver disease.

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    Weng, Xiufang; He, Ying; Visvabharathy, Lavanya; Liao, Chia-Min; Tan, Xiaosheng; Balakumar, Arjun; Wang, Chyung-Ru

    2017-10-01

    Natural killer T (NKT) cells are CD1d-restricted innate-like T cells that modulate innate and adaptive immune responses. Unlike the well-characterized invariant/type I NKT cells, type II NKT cells with a diverse T cell receptor repertoire are poorly understood. This study defines the pathogenic role of type II NKT cells in the etiology of chronic liver inflammation. Transgenic mice with the Lck promoter directing CD1d overexpression on T cells in Jα18 wild-type (Lck-CD1dTgJα18 + ; type I NKT cell sufficient) and Jα18-deficient (Lck-CD1dTgJα18 o , type I NKT cell deficient) mice were analyzed for liver pathology and crosstalk between type II NKT cells and conventional T cells. CD1d expression on T cells in peripheral blood samples and liver sections from autoimmune hepatitis patients and healthy individuals were also examined. Lck-CD1dTgJα18 o and Lck-CD1dTgJα18 + mice developed similar degrees of liver pathology resembling chronic autoimmune hepatitis in humans. Increased CD1d expression on T cells promoted the activation of type II NKT cells and other T cells. This resulted in T h 1-skewing and impaired T h 2 cytokine production in type II NKT cells. Dysfunction of type II NKT cells was accompanied by conventional T cell activation and pro-inflammatory cytokine production, leading to a hepatic T/B lymphocyte infiltration, elevated autoantibodies and hepatic injury in Lck-CD1dTg mice. A similar mechanism could be extended to humans as CD1d expression is upregulated on activated human T cells and increased presence of CD1d-expressing T cells was observed in autoimmune hepatitis patients. Our data reveals enhanced crosstalk between type II NKT cells and conventional T cells, leading to a T h 1-skewed inflammatory milieu, and consequently, to the development of chronic autoimmune liver disease. Lay summary: CD1d overexpression on T cells enhances crosstalk between type II NKT cells and T cells, resulting in their aberrant activation and leading to the

  10. Prevalence of hepatobiliary dysfunction in a regional group of patients with chronic inflammatory bowel disease

    DEFF Research Database (Denmark)

    Wewer, V; Gluud, C; Schlichting, P

    1991-01-01

    A regional group of outpatients with chronic inflammatory bowel disease (ulcerative colitis, n = 396, and Crohn's disease, n = 125) was biochemically screened to estimate the prevalence of hepatobiliary dysfunction. Among the 396 patients with ulcerative colitis, 69 (17%; 95% confidence limits, 14...... primary sclerosing cholangitis, of whom two were primarily diagnosed; one patient had cholangiocarcinoma also primarily diagnosed; and two patients were found to have alcoholic hepatic damage. Among the 125 patients with Crohn's disease, 38 (30%; 95% confidence limits, 23-38%) had at least 1 abnormal...... the criteria for further evaluation as described above. One patient appeared to have epithelioid granuloma in the liver and one patient had alcoholic liver disease, whereas one patient refused further examination.(ABSTRACT TRUNCATED AT 250 WORDS)...

  11. Hypothalamic GPR40 Signaling Activated by Free Long Chain Fatty Acids Suppresses CFA-Induced Inflammatory Chronic Pain

    OpenAIRE

    Nakamoto, Kazuo; Nishinaka, Takashi; Sato, Naoya; Mankura, Mitsumasa; Koyama, Yutaka; Kasuya, Fumiyo; Tokuyama, Shogo

    2013-01-01

    GPR40 has been reported to be activated by long-chain fatty acids, such as docosahexaenoic acid (DHA). However, reports studying functional role of GPR40 in the brain are lacking. The present study focused on the relationship between pain regulation and GPR40, investigating the functional roles of hypothalamic GPR40 during chronic pain caused using a complete Freund's adjuvant (CFA)-induced inflammatory chronic pain mouse model. GPR40 protein expression in the hypothalamus was transiently inc...

  12. Gliopathy of Demyelinating And Non-Demyelinating Strains Of Mouse Hepatitis Virus.

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    Lawrence Charles Kenyon

    2015-12-01

    Full Text Available Demyelination in the central nervous system induced by neurovirulent strains of Mouse Hepatitis Virus (MHV is mediated by the viral spike glycoprotein, but it is not clear whether the mechanism of this disease pathology involves direct viral infection of oligodendrocytes. Detailed studies of glial cell tropism of MHV are presented, demonstrating that direct MHV infection of oligodendrocytes differs between demyelinating (RSA59 and non-demyelinating (RSMHV2 viral strains both in vitro and in vivo. Our results indicate that direct injury of mature oligodendrocytes is an important mechanism of virus-induced demyelination. In vivo, RSA59 infection was identified in spinal cord gray and white matter, but infected oligodendrocytes were restricted to white matter. In contrast, RSMHV2 infection was restricted to gray matter neurons and was not localized to oligodendrocytes. In vitro, RSA59 can infect both oligodendrocyte precursors and differentiated oligodendrocytes, whereas RSMHV2 can infect oligodendrocyte precursors but not differentiated oligodendrocytes. Viral spreading through axonal means to white matter and release of the demyelinating strain MHV at the nerve end is critical for oligodendrocytes infection and subsequent demyelination. Understanding the mechanisms by which known viruses effect demyelination in this animal model has important therapeutic implications in the treatment of human demyelinating disease.

  13. The Economic Impact of Biosimilars on Chronic Immune-Mediated Inflammatory Diseases.

    Science.gov (United States)

    Pentek, Marta; Zrubka, Zsombor; Gulacsi, Laszlo

    2017-01-01

    Biological drugs represent highly effective but costly treatments for chronic immunemediated inflammatory diseases posing substantial burden on health care budgets. Introduction of biosimilars since 2013 has brought forward the potential of market competition, and as a societal benefit, the hope of increased access at a lower cost. We aim to provide a descriptive review on economic aspects and market changes related to the introduction of biosimilar drugs. Our focus is on chronic immune-mediated inflammatory conditions in rheumatology, gastroenterology and dermatology. Based on available literature data, we discuss the determinants of access to biological treatment, summarize the available health economic evidences with special focus on cost-utility and budget impact analyses. Market penetration of biosimilars and their overall impact on biological markets are analyzed. Biosimilar markets are country specific due to differences in the regulatory and reimbursement systems. Cost-utility analyses suggest, that given the lower price of biosimilars, formerly established biological treatment sequence practices and the eligibility criteria for biological treatment deserve reconsideration. Budget impact analyses forecasted significant budget savings in various diagnoses and countries, providing opportunity for the treatment of more patients. Biosimilars may contribute to better patient-access and provide savings to governments. To increase their acceptability, further clinical evidences and real world experiences are needed, as well as education of physicians and patients. The high biosimilar penetration rates in Norway, Denmark and Poland suggest that policies which support interchanging from the reference product may be important drivers of biosimilar uptake. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. Applicability of the EULAR recommendations on the role of the nurse in the management of chronic inflammatory arthritis in Portugal Applicability of the EULAR recommendations on the role of the nurse in the management of chronic inflammatory arthritis in Portugal

    NARCIS (Netherlands)

    Barbosa, L.; Ramiro, S.; Santos, M. J.; Canas da Silva, J.

    2013-01-01

    Objectives: To evaluate the level of agreement and applicability of the EULAR recommendations for the role of the nurse in the management of chronic inflammatory arthritis in Portugal. Methods: Nurses from all Portuguese rheumatology centers were invited to fill-in a questionnaire addressing the

  15. Marked QTc prolongation and Torsades de Pointes in patients with chronic inflammatory arthritis

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    Pietro Enea Lazzerini

    2016-09-01

    Full Text Available Mounting evidence indicates that in chronic inflammatory arthritis (CIA, QTc prolongation is frequent and correlates with systemic inflammatory activation. Notably, basic studies demonstrated that inflammatory cytokines induce profound changes in potassium and calcium channels resulting in a prolonging effect on cardiomyocyte action potential duration (APD, thus on the QT interval on the electrocardiogram. Moreover, it has been demonstrated that in RA patients the risk of SCD is significantly increased when compared to non-RA subjects. Conversely, to date no data are available about Torsades de Pointes (TdP prevalence in CIA, and the few case reported considered CIA only an incidental concomitant disease, not contributing factor to TdP development.We report three patients with active CIA developing marked QTc prolongation, in two cases complicated with TdP degenerating to cardiac arrest. In these patients, a blood sample was obtained within 24h from TdP/marked QTc prolongation occurrence and levels of IL-6, TNF-alpha and IL-1 were evaluated. In all three cases, IL-6 was markedly elevated, ~10 to 100 times more than reference values. Moreover, one patient also showed high circulating levels of TNF-alpha and IL-1. In conclusion, active CIA may represent a currently overlooked QT-prolonging risk factor, potentially contributing in the presence of other classical risk factors to TdP occurrence. In particular, a relevant role may be played by elevated circulating IL-6 levels via direct electrophysiological effects on the heart. This observation should be carefully kept in mind, particularly when recognizable risk factors are already present and/or the addition of QT-prolonging drugs is required.

  16. Pro-/anti-inflammatory cytokine gene polymorphisms and chronic kidney disease: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Okada Rieko

    2012-01-01

    Full Text Available Abstract Background The aim of this study was to explore the associations between common potential functional promoter polymorphisms in pro-/anti-inflammatory cytokine genes and kidney function/chronic kidney disease (CKD prevalence in a large Japanese population. Methods A total of 3,323 subjects aged 35-69 were genotyped for all 10 single nucleotide polymorphisms (SNPs in the promoter regions of candidate genes with minor allele frequencies of > 0.100 in Japanese populations. The estimated glomerular filtration rate (eGFR and CKD prevalence (eGFR 2 of the subjects were compared among the genotypes. Results A higher eGFR and lower prevalence of CKD were observed for the homozygous variants of IL4 -33CC (high IL-4 [anti-inflammatory cytokine]-producing genotype and IL6 -572GG (low IL-6 [pro-inflammatory cytokine]-producing genotype. Subjects with IL4 CC + IL6 GG showed the highest mean eGFR (79.1 ml/min/1.73 m2 and lowest CKD prevalence (0.0%, while subjects carrying IL4 TT + IL6 CC showed the lowest mean eGFR (73.4 ml/min/1.73 m2 and highest CKD prevalence (17.9%. Conclusions The functional promoter polymorphisms IL4 T-33C (rs2070874 and IL6 C-572G (rs1800796, which are the only SNPs that affect the IL-4 and IL-6 levels in Japanese subjects, were associated with kidney function and CKD prevalence in a large Japanese population.

  17. SORPTION РATHOGENETIC THERAPY OF ENDOGENOUS INTOXICATION OF PEDIATRIC CHRONIC INFLAMMATORY BOWEL DISEASES

    Directory of Open Access Journals (Sweden)

    O.V. Fedorova

    2009-01-01

    Full Text Available Gut endotoxicosis caused by penetration of bacterial and metabolic toxins from chime on the background of increasing permeability of gut wall is of great importance in pathogenesis of chronic inflammatory bowel diseases (nonspecific ulcerative colitis — NUC and Crohn’s disease. It is accompanied by disturbance of regulating homeostasis system with the following disturbances of organs and systems of toxication. Developed endotoxicosis accordingly contributes to maintain and to progress of metabolic and immunological changes. To obtain the precise degree and phase of development of endotoxicosis we estimated quantitative and qualitative changes of metabolic status in accordance with content in erythrocytes, plasma and urine LMMWP (low and medium molecular weight peptides. Taking into concideration the peculiarities of children endotoxicosis with, we suggested patogenetical absorption therapy. Therefore, the therapeutic complex was added enterosorbent ensoral, which absorb eczo and endogenic toxins and, moreover, positive influence for composition of intestinal microflora. Prominent clinical effect was accompanied by positive dynamics of laboratory-instrumental parameters.Key words: endogenous intoxication, inflammatory bowel diseases, nonspecific ulcerative colitis, Crohn’s disease, low and medium molecular weight peptides, enterosorbents, children.

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

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    Wei-Chun Lin

    2015-01-01

    Full Text Available 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.

  19. Chronic administration of fluoxetine and pro-inflammatory cytokine change in a rat model of depression.

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    Yanxia Lu

    Full Text Available This study evaluated the chronic effects of fluoxetine, a commonly prescribed SSRI antidepressant, on the peripheral and central levels of inflammatory cytokines including IL-1β, IL-6, TNF-α and IL-17 over a 4-interval in a rat model of chronic mild stress (CMS which resembles the human experience of depression. Twenty-four Sprague-Dawley rats were randomly assigned to CMS+vehicle (n = 9, CMS+fluoxetine (n = 9 and the control (n = 6 groups. Sucrose preference and forced swim tests were performed to assess behavioral change. Blood samples were collected on day 0, 60, 90 and 120 for measurement of cytokine levels in plasma. On day 120, the brain was harvested and central level of cytokines was tested using Luminex. Four months of fluoxetine treatment resulted in changes in the sucrose preference and immobility time measurements, commensurate with antidepressant effects. The CMS+vehicle group exhibited elevated plasma levels of IL-1β, IL-17, and TNF-α on day 60 or 120. Rats treated with fluoxetine demonstrated lower IL-1β in plasma and brain after 90 and 120-day treatment respectively (p<0.05. There was a trend of reduction of IL-6 and TNF-α concentration. This study revealed the potential therapeutic effects of fluoxetine by reducing central and peripheral levels of IL-1β in the alleviation of depressive symptoms.

  20. Chronic administration of fluoxetine and pro-inflammatory cytokine change in a rat model of depression.

    Science.gov (United States)

    Lu, Yanxia; Ho, Cyrus S; Liu, Xin; Chua, Anna N; Wang, Wei; McIntyre, Roger S; Ho, Roger C

    2017-01-01

    This study evaluated the chronic effects of fluoxetine, a commonly prescribed SSRI antidepressant, on the peripheral and central levels of inflammatory cytokines including IL-1β, IL-6, TNF-α and IL-17 over a 4-interval in a rat model of chronic mild stress (CMS) which resembles the human experience of depression. Twenty-four Sprague-Dawley rats were randomly assigned to CMS+vehicle (n = 9), CMS+fluoxetine (n = 9) and the control (n = 6) groups. Sucrose preference and forced swim tests were performed to assess behavioral change. Blood samples were collected on day 0, 60, 90 and 120 for measurement of cytokine levels in plasma. On day 120, the brain was harvested and central level of cytokines was tested using Luminex. Four months of fluoxetine treatment resulted in changes in the sucrose preference and immobility time measurements, commensurate with antidepressant effects. The CMS+vehicle group exhibited elevated plasma levels of IL-1β, IL-17, and TNF-α on day 60 or 120. Rats treated with fluoxetine demonstrated lower IL-1β in plasma and brain after 90 and 120-day treatment respectively (pfluoxetine by reducing central and peripheral levels of IL-1β in the alleviation of depressive symptoms.

  1. Inflammatory stress promotes the development of obesity-related chronic kidney disease via CD36 in mice.

    Science.gov (United States)

    Yang, Ping; Xiao, Yayun; Luo, Xuan; Zhao, Yunfei; Zhao, Lei; Wang, Yan; Wu, Tingting; Wei, Li; Chen, Yaxi

    2017-07-01

    Ectopic fat located in the kidney has emerged as a novel cause of obesity-related chronic kidney disease (CKD). In this study, we aimed to investigate whether inflammatory stress promotes ectopic lipid deposition in the kidney and causes renal injury in obese mice and whether the pathological process is mediated by the fatty acid translocase, CD36. High-fat diet (HFD) feeding alone resulted in obesity, hyperlipidemia, and slight renal lipid accumulation in mice, which nevertheless had normal kidney function. HFD-fed mice with chronic inflammation had severe renal steatosis and obvious glomerular and tubular damage, which was accompanied by increased CD36 expression. Interestingly, CD36 deficiency in HFD-fed mice eliminated renal lipid accumulation and pathological changes induced by chronic inflammation. In both human mesangial cells (HMCs) and human kidney 2 (HK2) cells, inflammatory stress increased the efficiency of CD36 protein incorporation into membrane lipid rafts, promoting FFA uptake and intracellular lipid accumulation. Silencing of CD36 in vitro markedly attenuated FFA uptake, lipid accumulation, and cellular stress induced by inflammatory stress. We conclude that inflammatory stress aggravates renal injury by activation of the CD36 pathway, suggesting that this mechanism may operate in obese individuals with chronic inflammation, making them prone to CKD. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

  2. Interferon-gamma (IFN-gamma) treatment decreases the inflammatory response in chronic Pseudomonas aeruginosa pneumonia in rats

    DEFF Research Database (Denmark)

    Johansen, H K; Hougen, H P; Rygaard, J

    1996-01-01

    In a rat model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis (CF), we studied whether the inflammatory response could be altered by intraperitoneal treatment with recombinant rat interferon-gamma (rrIFN-gamma). Rats were treated either before or after intratracheal ch...

  3. Do serum ALAT values reflect the inflammatory activity in the liver of patients with chronic viral hepatitis?

    NARCIS (Netherlands)

    Cahen, D. L.; van Leeuwen, D. J.; ten Kate, F. J.; Blok, A. P.; Oosting, J.; Chamuleau, R. A.

    1996-01-01

    A retrospective study was carried out in 40 patients with chronic viral hepatitis, to assess whether serum alanine aminotransferase reflects the inflammatory process in the liver. Twenty liver biopsy specimens were included for each disease. Five histological aspects were scored: periportal

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

    Science.gov (United States)

    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

  5. α-blockers, antibiotics and anti-inflammatories have a role in the management of chronic prostatitis/chronic pelvic pain syndrome.

    Science.gov (United States)

    Thakkinstian, Ammarin; Attia, John; Anothaisintawee, Thunyarat; Nickel, J Curtis

    2012-10-01

    Study Type - Therapy (systematic review) Level of Evidence 1a. What's known on the subject? and What does the study add? Individual clinical trials evaluating antibiotics, anti-inflammatories and α-blockers for the treatment of chronic prostatitis/chronic pelvic pain syndrome have shown only modest or even no benefits for patients compared with placebo, yet we continue to use these agents in selected patients with some success in clinical practice. This network meta-analysis of current evidence from all available randomized placebo-controlled trials with similar inclusion criteria and outcome measures shows that these '3-As' of chronic prostatitis/chronic pelvic pain syndrome treatment (antibiotics, anti-inflammatories and α-blockers) do offer benefits to some patients, particularly if we use them strategically in selected individuals. To provide an updated network meta-analysis mapping α-blockers, antibiotics and anti-inflammatories (the 3-As) in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). • To use the results of this meta-analysis to comment on the role of the 3-As in clinical practice. We updated a previous review including only randomized controlled studies employing the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) as one of the outcomes to compare treatment effects in CP/CPPS patients. • A longitudinal mixed regression model (network meta-analysis) was applied to indirectly assess multiple treatment comparisons (i.e. α-blockers, antibiotics, anti-inflammatory/immune modulation therapies, α-blockers plus antibiotics, and placebo). Nineteen studies (1669 subjects) were eligible for analysis. • α-blockers, antibiotics and anti-inflammatory/immune modulation therapies were associated with significant improvement in symptoms when compared with placebo, with mean differences of total CPSI of -10.8 (95% CI -13.2 to -8.3; P antibiotics resulted in the greatest CPSI difference (-13.6, 95% CI -16.7 to -10.6; P

  6. Impact of red and processed meat and fibre intake on treatment outcomes among patients with chronic inflammatory diseases

    DEFF Research Database (Denmark)

    Christensen, Robin; Heitmann, Berit L; Andersen, Karina Winther

    2018-01-01

    INTRODUCTION: Chronic inflammatory diseases (CIDs) are frequently treated with biological medications, specifically tumour necrosis factor inhibitors (TNFi)). These medications inhibit the pro-inflammatory molecule TNF alpha, which has been strongly implicated in the aetiology of these diseases. Up...... with inflammatory bowel disease (Crohn's disease and ulcerative colitis), rheumatic disorders (rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis), inflammatory skin diseases (psoriasis, hidradenitis suppurativa) and non-infectious uveitis. At baseline (pretreatment), patient characteristics...... will be assessed using patient-reported outcome measures, clinical assessments of disease activity, quality of life and lifestyle, in addition to registry data on comorbidity and concomitant medication(s). In accordance with current Danish standards, follow-up will be conducted 14-16 weeks after treatment...

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

    Directory of Open Access Journals (Sweden)

    Wei Kevin Zhang

    2016-04-01

    Full Text Available 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.

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

    Directory of Open Access Journals (Sweden)

    Bosma-den Boer Margarethe M

    2012-04-01

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

  9. Demyelination versus remyelination in progressive multiple sclerosis

    DEFF Research Database (Denmark)

    Bramow, Stephan; Frischer, Josa M; Lassmann, Hans

    2010-01-01

    The causes of incomplete remyelination in progressive multiple sclerosis are unknown, as are the pathological correlates of the different clinical characteristics of patients with primary and secondary progressive disease. We analysed brains and spinal cords from 51 patients with progressive...... multiple sclerosis by planimetry. Thirteen patients with primary progressive disease were compared with 34 with secondary progressive disease. In patients with secondary progressive multiple sclerosis, we found larger brain plaques, more demyelination in total and higher brain loads of active demyelination...... compared with patients with primary progressive disease. In addition, the brain density of plaques with high-grade inflammation and active demyelination was highest in secondary progressive multiple sclerosis and remained ~18% higher than in primary progressive multiple sclerosis after adjustments...

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  11. Apolipoprotein E Mimetic Promotes Functional and Histological Recovery in Lysolecithin-Induced Spinal Cord Demyelination in Mice.

    Science.gov (United States)

    Gu, Zhen; Li, Fengqiao; Zhang, Yi Ping; Shields, Lisa B E; Hu, Xiaoling; Zheng, Yiyan; Yu, Panpan; Zhang, Yongjie; Cai, Jun; Vitek, Michael P; Shields, Christopher B

    2013-04-01

    Considering demyelination is the pathological hallmark of multiple sclerosis (MS), reducing demyelination and/or promoting remyelination is a practical therapeutic strategy to improve functional recovery for MS. An apolipoprotein E (apoE)-mimetic peptide COG112 has previously demonstrated therapeutic efficacy on functional and histological recovery in a mouse experimental autoimmune encephalomyelitis (EAE) model of human MS. In the current study, we further investigated whether COG112 promotes remyelination and improves functional recovery in lysolecithin induced focal demyelination in the white matter of spinal cord in mice. A focal demyelination model was created by stereotaxically injecting lysolecithin into the bilateral ventrolateral funiculus (VLF) of T8 and T9 mouse spinal cords. Immediately after lysolecithin injection mice were treated with COG112, prefix peptide control or vehicle control for 21 days. The locomotor function of the mice was measured by the beam walking test and Basso Mouse Scale (BMS) assessment. The nerve transmission of the VLF of mice was assessed in vivo by transcranial magnetic motor evoked potentials (tcMMEPs). The histological changes were also examined by by eriochrome cyanine staining, immunohistochemistry staining and electron microscopy (EM) method. The area of demyelination in the spinal cord was significantly reduced in the COG112 group. EM examination showed that treatment with COG112 increased the thickness of myelin sheaths and the numbers of surviving axons in the lesion epicenter. Locomotor function was improved in COG112 treated animals when measured by the beam walking test and BMS assessment compared to controls. TcMMEPs also demonstrated the COG112-mediated enhancement of amplitude of evoked responses. The apoE-mimetic COG112 demonstrates a favorable combination of activities in suppressing inflammatory response, mitigating demyelination and in promoting remyelination and associated functional recovery in animal model

  12. Therapeutic effect of aripiprazole in chronic schizophrenia is accompanied by anti-inflammatory activity.

    Science.gov (United States)

    Sobiś, Jarosław; Rykaczewska-Czerwińska, Monika; Świętochowska, Elżbieta; Gorczyca, Piotr

    2015-04-01

    Weight gain and metabolic abnormalities occur in chronic schizophrenia patients treated with atypical antipsychotics. The purpose of the study was to evaluate changes in serum levels of C-reactive protein (CRP), insulin and cytokines (IL-6, TNF-α, IL-1β, IFN-γ, sTNF-R1, IL-12, IL-23, IL-1Ra, TGF-β1, IL-4, and IL-10) after switching to aripiprazole. Cytokine, hsCRP and insulin measurements were performed in patients (n=17) on day 0 and day 28 of the study using standard ELISA assays. The psychopathological status was assessed using PANSS. WC and BMI were measured and calculated, respectively. We observed high clinical efficacy in aripiprazole linked to a 2.7% weight loss. There were statistically significant reductions in PANSS scores and body parameters (p<0.001). After 28 days we detected a significant reduction in hsCRP (p<0.001), insulin (p<0.001), IL-1β, IL-6, TNF-α, sTNF-R1, IL-12, IL-23, IL-1Ra, TGF-β1, IL-4 (p<0.001), IFN-γ (p<0.05) and a significant elevation of IL-10 (p<0.001). There was a significant negative correlation between IL-10 levels and PANSS positive, negative and total scores after the study (p=0.022, p=0.003, p=0.008, respectively). Aripiprazole limits inflammatory processes by enhancing anti-inflammatory signaling. Aripiprazole also reduces the risk of metabolic abnormalities. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  13. Caffeoylxanthiazonoside exerts cardioprotective effects during chronic heart failure via inhibition of inflammatory responses in cardiac cells.

    Science.gov (United States)

    Yang, Bin; Wang, Fei; Cao, Huili; Liu, Guifang; Zhang, Yuean; Yan, Ping; Li, Bao

    2017-11-01

    Caffeoylxanthiazonoside (CYT) is an active constituent isolated from the fruit of the Xanthium strumarium L plant. The aim of the present study was to investigate the cardioprotective effects of oral administration of CYT on chronic heart failure (CHF) and its underlying mechanisms. A rat model of CHF was first established, and cardiac function indices, including the heart/body weight index, left heart/body weight index, fractional shortening (FS), ejection fraction (EF), cardiac output (CO) and heart rate (HR), were subsequently determined by cardiac ultrasound. Serum levels of lactate dehydrogenase (LDH) and creatine kinase (CK), and the levels of pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β in heart tissues and cardiac microvascular endothelial cells (CMECs) were determined using ELISA. In addition, the protein expression levels of nuclear factor-κB (NF-κB) signaling pathway members were determined by western blotting in CMECs. The results demonstrated that oral administration of 10, 20, 40 mg/kg CYT significantly reduced cardiac hypertrophy and reversed FS, EF, CO and HR when compared with CHF model rats. In addition, CYT administration significantly decreased the levels of TNF-α, IL-6 and IL-1β in heart tissues, as well as serum LDH and CK levels. Furthermore, exposure of CMECs to 20, 40 and 80 µg/ml CYT significantly decreased the production of TNF-α, IL-1β and IL-6. The protein expression levels of cytoplasmic NF-κB p65 and IκB were upregulated, while nuclear NF-κB p65 was downregulated following treatment of CMECs with 20, 40 and 80 µg/ml CYT when compared with untreated CHF model controls. In conclusion, the results of the current study suggest that CYT demonstrates cardioprotective effects in CHF model rats by suppressing the expression of pro-inflammatory cytokines and the NF-κB signaling pathway.

  14. A Case of Paraneoplastic Demyelinating Motor Polyneuropathy

    Directory of Open Access Journals (Sweden)

    Sohrab Mostoufizadeh

    2012-04-01

    Full Text Available Peripheral neuropathy is commonly accompanied by cancer but demyelinating ones are not commonly reported. We report the clinical, neurophysiological, and biological characteristics of an 82-year-old patient who presented with a demyelinating motor neuropathy and high titre of anti-ganglioside antibodies associated with oesophageal cancer. The neurological course worsened rapidly despite immunotherapy, leading to a bedridden status. We propose to suspect a paraneoplastic origin in older patients or when the clinical course progresses rapidly within a few weeks or months.

  15. [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].

    Science.gov (United States)

    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).

  16. Pro-inflammatory cytokines and leukocyte oxidative burst in chronic kidney disease: culprits or innocent bystanders?

    Science.gov (United States)

    Neirynck, Nathalie; Glorieux, Griet; Schepers, Eva; Dhondt, Annemieke; Verbeke, Francis; Vanholder, Raymond

    2015-06-01

    Pro-inflammatory cytokines are elevated in chronic kidney disease (CKD), a condition characterized by microinflammation with oxidative stress as key feature. However, their role in the inflammatory response at uraemic concentrations has not yet been defined. In this study, the contribution of cytokines on induction of leukocyte oxidative stress was investigated. Whole blood from healthy donors was incubated with 20-1400 pg/mL TNFα, 5-102.8 pg/mL IL-6, 20-400 pg/mL IL-1β and 75-1200 pg/mL IL-18 separately or in combination. Oxidative burst was measured, at baseline and after stimulation with fMLP (Phagoburst™). The effect of the TNFα blocker, adalimumab (Ada), was evaluated on TNFα-induced ROS production. Finally, the association between TNFα and the composite end point all-cause mortality or first cardiovascular event was analysed in a CKD population stage 4-5 (n = 121). While interleukin (IL)-6, IL-1β and IL-18 alone induced no ROS activation of normal leukocytes, irrespective of concentrations, TNFα induced ROS activation at baseline (P < 0.01) and after fMLP stimulation (P < 0.05), but only at uraemic concentrations in the high range (400 and 1400 pg/mL). A similar pattern was observed with all cytokines in combination, but already at intermediate uraemic concentrations (all P < 0.05, except for monocytes after fMLP stimulation: n.s.), suggesting synergism between cytokines. ROS production induced by TNFα (400 pg/mL) and the cytokine combination was blocked with Ada. Uraemia-related oxidative stress in leukocytes of haemodialysis patients was however not blocked by Ada. In patients, TNFα was not associated to adverse events (HR: 1.52, 95% CI 0.81-2.85, P = 0.13). Among several pro-inflammatory cytokines, TNFα alone was pro-oxidative but only at high-range uraemic concentrations. Adding a TNFα blocker, Ada, blocked this ROS production, but not the oxidative stress in blood samples from haemodialysis patients, suggesting that other uraemic toxins than

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

    Directory of Open Access Journals (Sweden)

    Mahaveer Golechha

    2014-01-01

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

  18. Effects of chronic inflammatory bowel diseases on left ventricular structure and function: a study protocol

    Directory of Open Access Journals (Sweden)

    Botti Fiorenzo

    2002-09-01

    Full Text Available Abstract Background Experimental evidences suggest an increased collagen deposition in inflammatory bowel diseases (IBD. In particular, large amounts of collagen type I, III and V have been described and correlated to the development of intestinal fibrotic lesions. No information has been available until now about the possible increased collagen deposition far from the main target organ. In the hypothesis that chronic inflammation and increased collagen metabolism are reflected also in the systemic circulation, we aimed this study to evaluate the effects on left ventricular wall structure by assessing splancnic and systemic collagen metabolism (procollagen III assay, deposition (ultrasonic tissue characterization, and cardiac function (echocardiography in patients with different long standing history of IBD, before and after surgery. Methods Thirty patients affected by active IBD, 15 with Crohn and 15 with Ulcerative Colitis, submitted to surgery will be enrolled in the study in a double blind fashion. They will be studied before the surgical operation and 6, 12 months after surgery. A control group of 15 healthy age and gender-matched subjects will also be studied. At each interval blood samples will be collected in order to assess the collagen metabolism; a transthoracic echocardiogram will be recorded for the subsequent determination of cardiac function and collagen deposition. Discussion From this study protocol we expect additional information about the association between IBD and cardiovascular disorders; in particular to address the question if chronic inflammation, through the altered collagen metabolism, could affect left ventricular structure and function in a manner directly related to the estimated duration of the disease.

  19. Evaluation of the inflammatory activity in chronic osteomyelitis. Contribution of the scintigraphy with polyclonal antibodies

    International Nuclear Information System (INIS)

    Sapienza, Marcelo Tatit

    1996-01-01

    Active chronic osteomyelitis or complicating osteomyelitis (superimposed on diseases that changes the normal bone structure fractures, post-surgery, prosthesis) can be difficult to diagnose by anatomic radiological imaging modalities, like plain radiograph and CT. These diseases frequently cause also increased bone remodeling, leading to nonspecific uptake of Tc-99m-bone scan agents and gallium-67. New radiopharmaceuticals with greater inflammation/infection avidity and specificity are being developed, including the nonspecific polyclonal immunoglobulin (IgG) labeled with technetium-99. Tc-99m-IgG may be available as a ready to use kit, with no reported side effects, low patient absorbed radiation dose and low cost. The mechanism of IgG uptake at the inflammation site has not been fully elucidated yet. Specific (receptor linking, physico-chemical immunoglobulin properties) and nonspecific mechanisms (enhanced vascular permeability and macromolecular exudate) has been suggested. IgG scintigraphy results are affected by the isotope, labeling procedure adopted and characteristics of the inflammatory focus. Nineteen patients with suspected osteomyelitis (active chronic osteomyelitis or violated bone osteomyelitis) were studied by Tc-99m-IgG scintigraphy (directly labeled polyclonal immunoglobulin, Sandoglobuilina - Sandoz). All patients also underwent standard three-phase bone scintigraphy using methylene diphosphonate (Tc-99m-MDP), gallium-67 scintigraphy and plain radiographs. Infection was found in 8 sites. Sensitivity and specificity for Tc-99m-MDP, gallium-67 and Tc 99m-IgG scintigraphy were, respectively, 88 and 36%, 75 and 73%,88 and 82%. All patients with false positive IgG scintigraphies had previous surgery. Other current scintigraphic procedures used in the diagnosis of osteomyelitis are also reviewed. (author)

  20. Imaging of demyelinating and degenerative diseases of the brain

    International Nuclear Information System (INIS)

    Drayer, B.P.

    1987-01-01

    The emergence of cross-sectional brain imaging in the past decade has greatly expanded the role of imaging as a primary diagnostic modality for demyelinating and degenerative brain disorders. To remain an effective neurologic consultant, the radiologist must better understand the neuropathology and functional significance of these disorders. MR imaging has become the dominant imaging modality for multiple sclerosis and all demyelinating and dysmyelinating disorders. Detection is most sensitive with intermediate and T2-weighted spin-echo pulse sequences. Although increased signal intensity in the white matter is a sensitive but nonspecific finding, a knowledge of the patient's history and disease pathoanatomy greatly improves diagnostic specificity. Since an increasing proportion of the population is over 65 years of age, the distinction of normal versus pathologic aging becomes critical. The role of imaging in dementing illness is to distinguish primary degenerative dementia from normal aging changes, vascular medullary artery distribution disease, microangiopathic leukoencephalopathy, communicating hydrocephalus, and mass lesions. The role of MR imaging, including brain iron mapping, is analyzed in bradykinetic, choreiform, and dystonic disorders. The complications of chronic ethanol abuse, including vermian atrophy, central pontine myelinolysis, and Wernicke encephalopathy, are also reviewed

  1. A dysbiosis index to assess microbial changes in fecal samples of dogs with chronic inflammatory enteropathy.

    Science.gov (United States)

    AlShawaqfeh, M K; Wajid, B; Minamoto, Y; Markel, M; Lidbury, J A; Steiner, J M; Serpedin, E; Suchodolski, J S

    2017-11-01

    Recent studies have identified various bacterial groups that are altered in dogs with chronic inflammatory enteropathies (CE) compared to healthy dogs. The study aim was to use quantitative PCR (qPCR) assays to confirm these findings in a larger number of dogs, and to build a mathematical algorithm to report these microbiota changes as a dysbiosis index (DI). Fecal DNA from 95 healthy dogs and 106 dogs with histologically confirmed CE was analyzed. Samples were grouped into a training set and a validation set. Various mathematical models and combination of qPCR assays were evaluated to find a model with highest discriminatory power. The final qPCR panel consisted of eight bacterial groups: total bacteria, Faecalibacterium, Turicibacter, Escherichia coli, Streptococcus, Blautia, Fusobacterium and Clostridium hiranonis. The qPCR-based DI was built based on the nearest centroid classifier, and reports the degree of dysbiosis in a single numerical value that measures the closeness in the l2 - norm of the test sample to the mean prototype of each class. A negative DI indicates normobiosis, whereas a positive DI indicates dysbiosis. For a threshold of 0, the DI based on the combined dataset achieved 74% sensitivity and 95% specificity to separate healthy and CE dogs. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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

    Science.gov (United States)

    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.

  3. Bone mineral density and nutritional status in children with chronic inflammatory bowel disease

    NARCIS (Netherlands)

    A.M. Boot (Annemieke); J. Bouquet (Jan); E.P. Krenning (Eric); S.M.P.F. de Muinck Keizer-Schrama (Sabine)

    1998-01-01

    textabstractBACKGROUND: Osteoporosis has been reported in adult patients with inflammatory bowel disease. AIMS: To evaluate bone mineral density (BMD), nutritional status, and determinants of BMD in children with inflammatory bowel disease. PATIENTS: Fifty five patients

  4. The possibility of evaluation on inflammatory change at respiratory tract in chronic bronchial asthma using 67Ga scintigraphy

    International Nuclear Information System (INIS)

    Fukumitsu, Nobuyoshi; Uchiyama, Mayuki; Mori, Yutaka; Kawakami, Kenji; Kikuchi, Ichiro; Shimada, Takao.

    1997-01-01

    67 Ga scintigraphy was performed in 17 patients with chronic bronchial asthma to grasp the inflammatory change of respiratory tract. On 67 Ga scintigraphy, abnormal accumulations were detected on lung fields in 6 cases (35.3%) of 17 cases. In 5 cases of these 6 cases, the defect areas which were pointed out on 81m Kr ventilation scintigraphy were matched to the abnormal accumulation areas which were pointed out on 67 Ga scintigraphy. In dynamics, the abnormal accumulation areas which were pointed out on 67 Ga scintigraphy were matched to the defect areas which had been at all times pointed out on 81m Kr ventilation scintigraphy. 67 Ga scintigraphy was expected to be one of index to grasp the inflammatory change of respiratory tract in patients with chronic bronchial asthma. (author)

  5. Chronic orbital inflammatory disease and optic neuropathy associated with long-term intranasal cocaine abuse: 2 cases and literature review.

    Science.gov (United States)

    Siemerink, Martin J; Freling, Nicole J M; Saeed, Peerooz

    2017-10-01

    Orbital inflammatory disease and secondary optic neuropathy is a rare but devastating complication of long-term intranasal cocaine abuse. We describe 2 patients with a history of intranasal cocaine consumption who presented with subacute onset of unilateral vision loss from optic neuropathy and limitation of abduction in the affected eye. Magnetic resonance imaging findings included an orbital mass in combination with absent nasal septum and partial destruction of the paranasal sinuses. Biopsies and histopathologic examination of the nasal cavity and the orbital mass revealed chronic inflammation. Both patients were treated with oral corticosteroids, ocular movements completely normalized but no improvement of visual acuity was noted. Intranasal cocaine abuse can cause orbital complications from chronic sinonasal inflammatory disease and these patients are at risk to develop optic neuropathy. Optic neuropathy may be caused by compression, infiltration, or ischaemia.

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

    Directory of Open Access Journals (Sweden)

    E.M.A. Macedo

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-06-20

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

  8. Production of inflammatory cytokines by peripheral blood monocytes in chronic alcoholism: relationship with ethanol intake and liver disease.

    Science.gov (United States)

    Laso, Francisco Javier; Vaquero, José Miguel; Almeida, Julia; Marcos, Miguel; Orfao, Alberto

    2007-09-01

    Controversial results have been reported about the effects of alcoholism on the functionality of monocytes. In the present study we analyze the effects of chronic alcoholism on the intracellular production of inflammatory cytokines by peripheral blood (PB) monocytes. Spontaneous and in vitro-stimulated production of interleukin (IL) 1alpha (TNFalpha) by PB monocytes was analyzed at the single level by flow cytometry in chronic alcoholics without liver disease and active ethanol (EtOH) intake (AWLD group), as well as in patients with alcohol liver cirrhosis (ALC group), who were either actively drinking (ALCET group) or with alcohol withdrawal (ALCAW group). A significantly increased spontaneous production of IL1beta, IL6, IL12, and TNFalpha was observed on PB monocytes among AWLD individuals. Conversely, circulating monocytes form ALCET patients showed an abnormally low spontaneous and stimulated production of inflammatory cytokines. No significant changes were observed in ALCAW group as regards production of IL1beta, IL6, IL12, and TNFalpha. Our results show an altered pattern of production of inflammatory cytokines in PB monocytes from chronic alcoholic patients, the exact abnormalities observed depending on both the status of EtOH intake and the existence of alcoholic liver disease. Copyright 2007 Clinical Cytometry Society.

  9. Efficacy of supplemental anti-inflammatory therapy with fenspiride in chronic obstructive and nonobstructive bronchitis.

    Science.gov (United States)

    Volkova, L I; Budkova, A A; Filonova, N N; Khristolyubova, E I; Kutuzova, E B; Koroleva, N V; Radzivil, T T; Aminova, Z R; Chuchalin, A G

    2005-01-01

    The objective of this randomised, nonblind study was to assess the efficacy of fenspiride as complementary anti-inflammatory therapy in combination with ipratropium bromide in patients with chronic bronchitis (CB). A comparison was made with ipratropium bromide alone, the generally accepted standard therapy for CB. The study population comprised 20 patients with chronic obstructive bronchitis (COB) and 60 patients without signs of obstruction. Fifty-one males (64%) and 29 females (36%) aged from 25 to 65 years were studied over a 6-month treatment period. Combined therapy with fenspiride (160 mg/day) and ipratropium bromide (160 mug/day) was prescribed to 39 patients (28 with CB and 11 with COB) for 6 months, and monotherapy with ipratropium bromide (160 microg/day) was prescribed for 41 patients (32 with CB and nine with COB). The combined therapy group had a reduced intensity of dyspnoea, improvements in sputum nature and quantity of exudation, and a reduced intensity of coughing. The monotherapy group showed reductions in sputum exudation and cough intensity. Improvements in lung respiratory function were observed in both groups, but were greater in the combined therapy group of patients. Reduced cytosis, percentage and absolute content of neutrophils, and absolute content of lymphocytes and eosinophils in induced sputum were observed with CB patients in the combined therapy group. A reduced content of lymphocytes and an increase in macrophages were observed with CB patients in the monotherapy group. A significant decline in tumour necrosis factor (TNF)-alpha content in sputum was observed with both therapeutic regimens, although a statistically significant decline in serum TNFalpha (10.85 ng/L to 5.58 ng/L; p = 0.03) and reduced interleukin-8 in sputum (311.94 ng/L to 122.02 ng/L; p = 0.027) were observed with patients given combined therapy. The study showed greater efficacy of long-term treatment with fenspiride and ipratropium bromide compared with

  10. [Effect of tumour necrosis factor α blockade on bone metabolism in chronic inflammatory joint diseases].

    Science.gov (United States)

    Aguilar Del Rey, Francisco Javier; García Portales, Rosa; Haro Liger, Manuel; Rodríguez Andreu, José; Casals Sánchez, José Luis; Pérez González, Rita

    2016-07-15

    To evaluate the effect of anti-TNF treatments on bone mineral density (BMD), bone remodelling markers (BRM) and receptor activator of nuclear factor κB ligand (RANKL) and osteoprotegerin (OPG) in patients with chronic inflammatory joint diseases. A longitudinal prospective study was performed under clinical practice conditions on 31 patients diagnosed of rheumatoid arthritis, psoriatic arthropathy and ankylosing spondylitis who had received treatment with anti-TNF alpha drugs for one year. BMD, OPG and RANKL soluble form (sRANKL) were studied at the onset and end of the study. During the study (0, 3, 6, 9 and 12 month), disease activity (SDAI, BASDAI and CRP), functional capacity (HAQ, BASFI), BRM and vitamin D were studied. BMD was not modified after one year of treatment. The patients who took corticosteroids had a mean bone mass loss of 3% in the lumbar spine (±1.6, P=.02). In regards to the BRM, did not experience significant changes over the course of the study. Disease activity, both SDAI (P=.002) and BASDAI (P=.002), decreased. OPG was maintained without changes during the year of treatment while both the sRANKL (0.28±0.22, P=.013) and sRANKL/OPG ratio significantly decreased (0.04±0.03, P=.031). The patients being treated with anti-TNF did not present with a significant loss of DMO during the study (one year), at the same time experiencing an improvement in disease activity. This protection has been clearer in the responding patients. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

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

    Science.gov (United States)

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

    2015-10-01

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

  12. Multiple sclerosis deep grey matter: the relation between demyelination, neurodegeneration, inflammation and iron.

    Science.gov (United States)

    Haider, Lukas; Simeonidou, Constantina; Steinberger, Günther; Hametner, Simon; Grigoriadis, Nikolaos; Deretzi, Georgia; Kovacs, Gabor G; Kutzelnigg, Alexandra; Lassmann, Hans; Frischer, Josa M

    2014-12-01

    In multiple sclerosis (MS), diffuse degenerative processes in the deep grey matter have been associated with clinical disabilities. We performed a systematic study in MS deep grey matter with a focus on the incidence and topographical distribution of lesions in relation to white matter and cortex in a total sample of 75 MS autopsy patients and 12 controls. In addition, detailed analyses of inflammation, acute axonal injury, iron deposition and oxidative stress were performed. MS deep grey matter was affected by two different processes: the formation of focal demyelinating lesions and diffuse neurodegeneration. Deep grey matter demyelination was most prominent in the caudate nucleus and hypothalamus and could already be seen in early MS stages. Lesions developed on the background of inflammation. Deep grey matter inflammation was intermediate between low inflammatory cortical lesions and active white matter lesions. Demyelination and neurodegeneration were associated with oxidative injury. Iron was stored primarily within oligodendrocytes and myelin fibres and released upon demyelination. In addition to focal demyelinated plaques, the MS deep grey matter also showed diffuse and global neurodegeneration. This was reflected by a global reduction of neuronal density, the presence of acutely injured axons, and the accumulation of oxidised phospholipids and DNA in neurons, oligodendrocytes and axons. Neurodegeneration was associated with T cell infiltration, expression of inducible nitric oxide synthase in microglia and profound accumulation of iron. Thus, both focal lesions as well as diffuse neurodegeneration in the deep grey matter appeared to contribute to the neurological disabilities of MS patients. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  13. [Function and modulation of type Ⅱ innate lymphoid cells and their role in chronic upper airway inflammatory diseases].

    Science.gov (United States)

    Liu, Y; Liu, Z

    2017-02-07

    Type Ⅱ innate lymphoid cells (ILC2) is a family of innate immune lymphocytes, which provide effective immune responses to cytokines. ILC2 are regulated by the nuclear transcription factor ROR alpha and GATA3, secreting cytokines IL-5 and IL-13, etc. Animal models have shown that ILC2 are involved in allergic diseases, such as asthma and atopic dermatitis, and also play a very important role in the metabolic balance. In addition, recent reports suggest that ILC2 not only play a role in the initial stages of the disease, but also can lead to chronic pathological changes in the disease, such as fibrosis, and may have an effect on acquired immunity. This paper mainly focus in the role and regulation of ILC2 cells, and review the research status of ILC2 in the field of chronic upper airway inflammatory diseases including allergic rhinitis and chronic rhinosinusitis.

  14. Study of Low-grade Chronic Inflammatory Markers in Men with Central Obesity: Cathepsin S was Correlated with Waist Circumference

    Directory of Open Access Journals (Sweden)

    Adriana Todingrante

    2013-08-01

    Full Text Available BACKGROUND: There is a prevalence increase of overweight and obesity in Indonesia. Central obesity can lead a variety of chronic diseases through the inflammatory process. There are some markers for low-grade chronic inflammatory, such as cathepsin S, high sensitivity C-reactive protein (hs-CRP, interleukin-1- beta (IL-1β. To our current interest that central obesity can lead to various chronic diseases through the inflammatory process, we conducted a study to investigate correlation of Cathepsin S, hs-CRP, IL-1β in men with central obesity. METHODS: A cross-sectional study was conducted. Seventy-eight selected subjects were examined to collect anthropometric data and prepared for sample collection. Collected samples were processed for the following biochemical analyses: fasting glucose, high density lipoprotein (HDL-cholesterol, triglyceride, serum glutamic oxaloacetic transaminase (SGOT, serum glutamate pyruvate transaminase (SGPT, cathepsin S, hs-CRP, and IL-1β. Data distribution and variable correlation were then statistically analyzed. RESULTS: There were significant correlations between waist circumference (WC and cathepsin S (p=0.030; r=0.214, hs-CRP and cathepsin S (p=0.007; r=0.276, triglyceride and IL-1β (p=0.019; r=-0.235, WC and systolic blood pressure (SBP (p=0.003; r=-0.312, WC and fasting glucose (p=0.000; r=0.380, WC and body mass index (BMI (p=0.000; r=0.708. CONCLUSIONS: Our study showed that cathepsin S was correlated with central obesity, suggesting that cathepsin S could be a potential inflammatory marker in central obesity in the future. KEYWORDS: obesity, inflammation, hs-CRP, cathepsin S, IL-1β, waist circumference.

  15. Quercetin prevents chronic unpredictable stress induced behavioral dysfunction in mice by alleviating hippocampal oxidative and inflammatory stress.

    Science.gov (United States)

    Mehta, Vineet; Parashar, Arun; Udayabanu, Malairaman

    2017-03-15

    It is now evident that chronic stress is associated with anxiety, depression and cognitive dysfunction and very few studies have focused on identifying possible methods to prevent these stress-induced disorders. Previously, we identified abundance of quercetin in Urtica dioica extract, which efficiently attenuated stress related complications. Therefore, current study was designed to investigate the effect of quercetin on chronic unpredicted stress (CUS) induced behavioral dysfunction, oxidative stress and neuroinflammation in the mouse hippocampus. Animals were subjected to unpredicted stress for 21days, during which 30mg/kg quercetin was orally administered to them. Effect of CUS and quercetin treatment on animal behavior was assessed between day 22-26. Afterward, the hippocampus was processed to evaluate neuronal damage, oxidative and inflammatory stress. Results revealed that stressed animals were highly anxious (Elevated Plus Maze and Open Field), showed depressive-like behavior (sucrose preference task), performed poorly in short-term and long-term associative memory task (passive avoidance step-through task) and displayed reduced locomotion (open field). Quercetin alleviated behavioral dysfunction in chronically stressed animals. Compared to CUS, quercetin treatment significantly reduced anxiety, attenuated depression, improved cognitive dysfunction and normalized locomotor activity. Further, CUS elevated the levels of oxidative stress markers (TBARS, nitric oxide), lowered antioxidants (total thiol, catalase), enhanced expression of pro-inflammatory cytokines (IL-6, TNF-α, IL-1β and COX-2) in the hippocampus and damaged hippocampal neurons. Quercetin treatment significantly lowered oxidative and inflammatory stress and prevented neural damage. In conclusion, quercetin can efficiently prevent stress induced neurological complications by rescuing brain from oxidative and inflammatory stress. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Chronic restraint stress exacerbates nociception and inflammatory response induced by bee venom in rats: the role of the P2X7 receptors.

    Science.gov (United States)

    Li, Xiao-Qiu; Li, Man; Zhou, Zhong-He; Liu, Bao-Jun; Chen, Hui-Sheng

    2016-02-01

    Chronic restraint stress exacerbates pain and inflammation. The present study was designed to evaluate the effect of chronic restraint stress on inflammatory pain induced by subcutaneous injection of bee venom (BV). First, we investigated: (1) the effect of two-week restraint stress with daily 2 or 8 h on the baseline paw withdrawal mechanical threshold (PWMT), paw withdrawal thermal latency (PWTL) and paw circumference (PC); (2) the effect of chronic stress on the spontaneous paw-flinching reflex (SPFR), decrease in PWM, PWTL and increase in PC of the injected paw induced by BV. The results showed that (1) chronic restraint decreased significantly the PWMT and inhibited significantly the increase in PC, but had no effect on PWTL, compared with control group; (2) chronic restraint enhanced significantly BV-induced SPFR and inflammatory swelling of the injected paw. In a second series of experiments, the role of P2X7 receptor (P2X7R) in the enhancement of BV-induced inflammatory pain produced by chronic restraint stress was determined. Systemic pretreatment with P2X7R antagonist completely reversed the decrease in PWMT produced by chronic restraint, inhibited significantly the enhancement of BV-induced inflammatory pain produced by chronic restraint stress. Taken together, our data indicate that chronic restraint stress-enhanced nociception and inflammation in the BV pain model, possibly involving the P2X7R.

  18. Disease models of chronic inflammatory airway disease : applications and requirements for clinical trials

    NARCIS (Netherlands)

    Diamant, Zuzana; Clarke, Graham W.; Pieterse, Herman; Gispert, Juan

    Purpose of reviewThis review will discuss methodologies and applicability of key inflammatory models of respiratory disease in proof of concept or proof of efficacy clinical studies. In close relationship with these models, induced sputum and inflammatory cell counts will be addressed for

  19. Investigation of chronic efficacy and safety profile of two potential anti-inflammatory bipyrazole-based compounds in experimental animals

    Directory of Open Access Journals (Sweden)

    Domiati S

    2018-04-01

    Full Text Available Souraya Domiati,1 Mohammed Mehanna,2,3 Hanan Ragab,4 Hania Nakkash Chmaisse,1 Ahmed El Mallah5 1Department of Pharmacology and Therapeutics, Faculty of Pharmacy, Beirut Arab University, Beirut, Lebanon; 2Department of Pharmaceutical Technology, Faculty of Pharmacy, Beirut Arab University, Beirut, Lebanon; 3Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt; 4Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt; 5Department of Pharmacology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt Purpose: Although nonsteroidal anti-inflammatory drugs are widely used to treat a variety of disorders, their administration is associated with gastrointestinal side effects, acute kidney injury and liver enzymes’ elevation. Accordingly, researchers are encouraged to create novel agents with better safety profile. The aim of the current study was to evaluate the chronic efficacy and safety profile of two compounds previously proven to have acceptable acute anti-inflammatory and analgesic activities.Materials and methods: Doses were determined through formalin-induced mice paw edema-based dose–response curves. Granuloma weight was used to assess the chronic effect of the investigated compounds as compared to the vehicle and diclofenac representing the positive and the negative controls, respectively. Mice kidneys, livers and stomachs were histologically examined. Moreover, troponin I, alanine aminotransferase, aspartate aminotransferase, serum creatinine and blood urea nitrogen levels were measured. Results: The results highlight that the granulomas and exudates developed in mice after 7 days of treatment, with compound I and compound II were significantly lower than that of the negative control group. Moreover, compound I showed significantly better anti-inflammatory effect than diclofenac. Troponin level was undetected in all groups. Histopathological

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

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    Mary Anna Venneri

    Full Text Available 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

  1. Sympathetic Nerve Hyperactivity in the Spleen: Causal for Nonpathogenic-Driven Chronic Immune-Mediated Inflammatory Diseases (IMIDs?

    Directory of Open Access Journals (Sweden)

    Denise L. Bellinger

    2018-04-01

    Full Text Available Immune-Mediated Inflammatory Diseases (IMIDs is a descriptive term coined for an eclectic group of diseases or conditions that share common inflammatory pathways, and for which there is no definitive etiology. IMIDs affect the elderly most severely, with many older individuals having two or more IMIDs. These diseases include, but are not limited to, type-1 diabetes, obesity, hypertension, chronic pulmonary disease, coronary heart disease, inflammatory bowel disease, and autoimmunity, such as rheumatoid arthritis (RA, Sjőgren’s syndrome, systemic lupus erythematosus, psoriasis, psoriatic arthritis, and multiple sclerosis. These diseases are ostensibly unrelated mechanistically, but increase in frequency with age and share chronic systemic inflammation, implicating major roles for the spleen. Chronic systemic and regional inflammation underlies the disease manifestations of IMIDs. Regional inflammation and immune dysfunction promotes targeted end organ tissue damage, whereas systemic inflammation increases morbidity and mortality by affecting multiple organ systems. Chronic inflammation and skewed dysregulated cell-mediated immune responses drive many of these age-related medical disorders. IMIDs are commonly autoimmune-mediated or suspected to be autoimmune diseases. Another shared feature is dysregulation of the autonomic nervous system and hypothalamic pituitary adrenal (HPA axis. Here, we focus on dysautonomia. In many IMIDs, dysautonomia manifests as an imbalance in activity/reactivity of the sympathetic and parasympathetic divisions of the autonomic nervous system (ANS. These major autonomic pathways are essential for allostasis of the immune system, and regulating inflammatory processes and innate and adaptive immunity. Pathology in ANS is a hallmark and causal feature of all IMIDs. Chronic systemic inflammation comorbid with stress pathway dysregulation implicate neural-immune cross-talk in the etiology and pathophysiology of IMIDs

  2. Screening of traditional Chinese medicines with therapeutic potential on chronic obstructive pulmonary disease through inhibiting oxidative stress and inflammatory response.

    Science.gov (United States)

    Zhou, Ming-Xing; Wei, Xuan; Li, Ai-Ling; Wang, Ai-Min; Lu, Ling-Zi; Yang, Yue; Ren, Dong-Mei; Wang, Xiao-Ning; Wen, Xue-Sen; Lou, Hong-Xiang; Shen, Tao

    2016-09-13

    Chronic obstructive pulmonary disease (COPD) is a major public health problem and gives arise to severe chronic morbidity and mortality in the world. Inflammatory response and oxidative stress play dominant roles in the pathological mechanism of COPD, and have been regarded to be two important targets for the COPD therapy. Traditional Chinese medicines (TCMs) possess satisfying curative effects on COPD under guidance of the TCM theory in China, and merit in-depth investigations as a resource of lead compounds. One hundred ninety-six of TCMs were collected, and extracted to establish a TCM extract library, and then further evaluated for their potency on inhibitions of oxidative stress and inflammatory response using NADP(H):quinone oxidoreductase (QR) assay and nitric oxide (NO) production assay, respectively. Our investigation observed that 38 of the tested TCM extracts induced QR activity in hepa 1c1c7 murine hepatoma cells, and 55 of them inhibited NO production in RAW 264.7 murine macrophages at the tested concentrations. Noteworthily, 20 of TCM extracts simultaneously inhibited oxidative stress and inflammatory responses. The observed bioactive TCMs, particularly these 20 TCMs with dual inhibitory effects, might be useful for the treatment of COPD. More importantly, the results of the present research afford us an opportunity to discover new lead molecules as COPD therapeutic agents from these active TCMs.

  3. Tamsulosin Monotherapy versus Combination Therapy with Antibiotics or Anti-Inflammatory Agents in the Treatment of Chronic Pelvic Pain Syndrome

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    Tae Hyo Kim

    2011-06-01

    Full Text Available Purpose Chronic pelvic pain syndrome (CPPS is treated by use of various protocols. We compared tamsulosin monotherapy with tamsulosin in combination with antibiotics or anti-inflammatory agents and evaluated the efficacy of these treatments in patients with CPPS. Methods Patients (n=107 who were younger than 55 years and diagnosed with CPPS were randomly assigned to treatment with tamsulosin at 0.2 mg (group A, tamsulosin at 0.2 mg plus anti-inflammatory drugs (group B or tamsulosin at 0.2 mg plus antibiotics (group C daily. We applied the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI and the International Prostate Symptom Score (IPSS to evaluate 100 patients who were treated for 12 weeks (7 withdrew. Scores of the three groups were compared by analysis of variance and we also evaluated subscores, which included pain, voiding and quality of life (QoL. Results All three groups showed statistically significant decreases in NIH-CPSI score, IPSS and subscore scores (P<0.05. There were no statistically significant differences between the groups except for the QoL domain of the IPSS (group A vs. C; P<0.01. Conclusions Tamsulosin monotherapy for 12 weeks was effective for treating patients with CPPS, compared with combination therapy with antibiotics or anti-inflammatory drugs.

  4. Reducing inappropriate non-steroidal anti-inflammatory prescription in primary care patients with chronic kidney disease.

    Science.gov (United States)

    Keohane, David M; Dennehy, Thomas; Keohane, Kenneth P; Shanahan, Eamonn

    2017-08-14

    Purpose The purpose of this paper is to reduce inappropriate non-steroidal anti-inflammatory prescribing in primary care patients with chronic kidney disease (CKD). Once diagnosed, CKD management involves delaying progression to end stage renal failure and preventing complications. It is well established that non-steroidal anti-inflammatories have a negative effect on kidney function and consequently, all nephrology consensus groups suggest avoiding this drug class in CKD. Design/methodology/approach The sampling criteria included all practice patients with a known CKD risk factor. This group was refined to include those with an estimated glomerular filtration rate (eGFR)<60 ml/min per 1.73m2 (stage 3 CKD or greater). Phase one analysed how many prescriptions had occurred in this group over the preceding three months. The intervention involved creating an automated alert on at risk patient records if non-steroidal anti-inflammatories were prescribed and discussing the rationale with practice staff. The re-audit phase occurred three months' post intervention. Findings The study revealed 728/7,500 (9.7 per cent) patients at risk from CKD and 158 (2.1 per cent) who were subsequently found to have an eGFR<60 ml/min, indicating=stage 3 CKD. In phase one, 10.2 per cent of at risk patients had received a non-steroidal anti-inflammatory prescription in the preceding three months. Additionally, 6.2 per cent had received non-steroidal anti-inflammatories on repeat prescription. Phase two post intervention revealed a significant 75 per cent reduction in the total non-steroidal anti-inflammatories prescribed and a 90 per cent reduction in repeat non-steroidal anti-inflammatory prescriptions in those with CKD. Originality/value The study significantly reduced non-steroidal anti-inflammatory prescription in those with CKD in primary care settings. It also created a CKD register within the practice and an enduring medication alert system for individuals that risk nephrotoxic

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

    Science.gov (United States)

    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

  6. Biologics beyond TNF-α inhibitors and the effect of targeting the homologues TL1A-DR3 pathway in chronic inflammatory disorders

    DEFF Research Database (Denmark)

    Tougaard, Peter; Zervides, Kristoffer Alexander; Skov, Søren

    2016-01-01

    novel drugs that target TNF-α signaling are still being developed. Indeed, blockade of this pathway seems so important amongst immune-targets that TNF-α targeted therapies will continue to have a significant role in the treatment of chronic inflammation. However, up to 40% of RA and IBD patients do...... as a highly promising strategy for treatment of chronic inflammatory disorders....

  7. [STUDYING GASTRIC ULCERATION EFFECT OF A NEW DRUG INTENDED FOR TREATMENT OF CHRONIC INFLAMMATORY DISEASES OF KIDNEYS AND URINARY TRACT.

    Science.gov (United States)

    Murashko, T O; Smirnov, I V; Ivanov, A A; Postnikov, P S; Nemtsev, A O; Bondarev, A A; Udut, V V; Prisukhin, A N; Kornaukhov, A N; Sergeev, T S

    2016-08-01

    Gastric ulceration properties (gastrointestinal toxicity) of the sodium salt of 4-(0-β-D-glucopyranosyloxy) benzoic acid, a new nonsteroidal anti-inflammatory drug (NSAID) intended for the treatment of chronic inflammatory diseases of the kidney and urinary tract, have been tested on laboratory animals. Acute NSAID-induced gastropathy was induced in rats by oral administration of indomethacin, nimesulide, diclofenac, acetylsalicylic acid and the new drug. Test animals were killed by instantaneous decapitation 4 h after treatment and their gastrointestinal tracts were studied by pathomorphological methods on micropreparations and histological sections of gastric mucosa. It was established that the new drug, in contrast to reference NSAIDS, did not exhibit gastropathic action on the gastric mucosa.

  8. Acute Demyelination in a Person with Amphetamine Abuse

    Directory of Open Access Journals (Sweden)

    Serge Weis

    2011-01-01

    Full Text Available We report the case of a 31-year-old woman, admitted to the hospital for chest pain, dying a few days later from septic multiorgan failure, and showing at autopsy foci of acute demyelination in the occipital lobe. Gas chromatography/mass spectrometry analysis revealed the presence of amphetamine in the demyelinated area, which might be considered as the pathogenic agent, since other causes for demyelination could be excluded. This case represents the first report showing a demyelinating process due to a street drug.

  9. High Frequency of Chronic Bacterial and Non-Inflammatory Prostatitis in Infertile Patients with Prostatitis Syndrome Plus Irritable Bowel Syndrome

    Science.gov (United States)

    Vicari, Enzo; La Vignera, Sandro; Arcoria, Domenico; Condorelli, Rosita; Vicari, Lucia O.; Castiglione, Roberto; Mangiameli, Andrea; Calogero, Aldo E.

    2011-01-01

    Background Although prostatitis syndrome (PS) and irritable bowel syndrome (IBS) are common disorders, information on the prevalence of IBS in infertile patients with PS is relatively scanty. Therefore, this study was undertaken to estimate the frequency of PS and IBS and to evaluate the prevalence of the various diagnostic categories of prostatitis. Methodology/Principal Findings This study enrolled 152 patients with PS, diagnosed by the NIH-Chronic Prostatitis Symptom Index (NIH-CPSI) in an andrological setting, and 204 patients with IBS, diagnosed according to the Rome III diagnostic criteria in a gastroenterological setting. The patients with PS were asked to fulfill the Rome III questionnaire for IBS, whereas patients with IBS were asked to complete the NIH-CPSI. The simultaneous presence of PS and IBS was observed in 30.2% and 31.8% of the patients screened by andrologists and gastroenterologists, respectively. Altogether, 111 patients had PS plus IBS (31.2%). They had a total NIH-CPSI and pain subscale scores significantly higher than patients with PS alone. Gastrointestinal symptoms in patients with PS plus IBS were similar to those reported by patients with IBS alone and significantly greater in patients with PS alone. Patients with PS plus IBS had a significantly higher frequency of chronic bacterial prostatitis (category II) and lower of non-inflammatory prostatitis (category IIIB), compared to patients with PS alone. The frequency of inflammatory prostatitis (category IIIA) resulted similar. Conclusions/Significance Prostatitis syndromes and IBS are frequently associated in patients with PS- or IBS-related symptoms. These patients have an increased prevalence of chronic bacterial and non-inflammatory prostatitis. PMID:21494624

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

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    Abderaouf Damouche

    2015-09-01

    Full Text Available 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

  11. High frequency of chronic bacterial and non-inflammatory prostatitis in infertile patients with prostatitis syndrome plus irritable bowel syndrome.

    Directory of Open Access Journals (Sweden)

    Enzo Vicari

    2011-04-01

    Full Text Available Although prostatitis syndrome (PS and irritable bowel syndrome (IBS are common disorders, information on the prevalence of IBS in infertile patients with PS is relatively scanty. Therefore, this study was undertaken to estimate the frequency of PS and IBS and to evaluate the prevalence of the various diagnostic categories of prostatitis.This study enrolled 152 patients with PS, diagnosed by the NIH-Chronic Prostatitis Symptom Index (NIH-CPSI in an andrological setting, and 204 patients with IBS, diagnosed according to the Rome III diagnostic criteria in a gastroenterological setting. The patients with PS were asked to fulfill the Rome III questionnaire for IBS, whereas patients with IBS were asked to complete the NIH-CPSI. The simultaneous presence of PS and IBS was observed in 30.2% and 31.8% of the patients screened by andrologists and gastroenterologists, respectively. Altogether, 111 patients had PS plus IBS (31.2%. They had a total NIH-CPSI and pain subscale scores significantly higher than patients with PS alone. Gastrointestinal symptoms in patients with PS plus IBS were similar to those reported by patients with IBS alone and significantly greater in patients with PS alone. Patients with PS plus IBS had a significantly higher frequency of chronic bacterial prostatitis (category II and lower of non-inflammatory prostatitis (category IIIB, compared to patients with PS alone. The frequency of inflammatory prostatitis (category IIIA resulted similar.Prostatitis syndromes and IBS are frequently associated in patients with PS- or IBS-related symptoms. These patients have an increased prevalence of chronic bacterial and non-inflammatory prostatitis.

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

    Science.gov (United States)

    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, PTEMs (30.9 ± 3.6% in STZ+SILD vs. 6.9 ± 2.7% in STZ, P 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-organ diabetic complications.

  13. B Cell, Th17, and Neutrophil Related Cerebrospinal Fluid Cytokine/Chemokines Are Elevated in MOG Antibody Associated Demyelination.

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    Kavitha Kothur

    Full Text Available Myelin oligodendrocyte glycoprotein antibody (MOG Ab associated demyelination represents a subgroup of autoimmune demyelination that is separate from multiple sclerosis and aquaporin 4 IgG-positive NMO, and can have a relapsing course. Unlike NMO and MS, there is a paucity of literature on immunopathology and CSF cytokine/chemokines in MOG Ab associated demyelination.To study the differences in immunopathogenesis based on cytokine/chemokine profile in MOG Ab-positive (POS and -negative (NEG groups.We measured 34 cytokines/chemokines using multiplex immunoassay in CSF collected from paediatric patients with serum MOG Ab POS [acute disseminated encephalomyelitis (ADEM = 8, transverse myelitis (TM = 2 n = 10] and serum MOG Ab NEG (ADEM = 5, TM = 4, n = 9 demyelination. We generated normative data using CSF from 20 non-inflammatory neurological controls.The CSF cytokine and chemokine levels were higher in both MOG Ab POS and MOG Ab NEG demyelination groups compared to controls. The CSF in MOG Ab POS patients showed predominant elevation of B cell related cytokines/chemokines (CXCL13, APRIL, BAFF and CCL19 as well as some of Th17 related cytokines (IL-6 AND G-CSF compared to MOG Ab NEG group (all p<0.01. In addition, patients with elevated CSF MOG antibodies had higher CSF CXCL13, CXCL12, CCL19, IL-17A and G-CSF than patients without CSF MOG antibodies.Our findings suggest that MOG Ab POS patients have a more pronounced CNS inflammatory response with elevation of predominant humoral associated cytokines/chemokines, as well as some Th 17 and neutrophil related cytokines/chemokines suggesting a differential inflammatory pathogenesis associated with MOG antibody seropositivity. This cytokine/chemokine profiling provides new insight into disease pathogenesis, and improves our ability to monitor inflammation and response to treatment. In addition, some of these molecules may represent potential immunomodulatory targets.

  14. An index of the ratio of inflammatory to antiviral cell types mediates the effects of social adversity and age on chronic illness.

    Science.gov (United States)

    Simons, Ronald L; Lei, Man-Kit; Beach, Steven R H; Barr, Ashley B; Cutrona, Carolyn E; Gibbons, Frederick X; Philibert, Robert A

    2017-07-01

    It is assumed that both social stress and chronological age increase the risk of chronic illness, in part, through their effect on systemic inflammation. Unfortunately, observational studies usually employ single-marker measures of inflammation (e.g., Interleukin-6, C-reactive protein) that preclude strong tests for mediational effects. The present study investigated the extent to which the effects of socioeconomic disadvantage and age on onset of chronic illness is mediated by dominance of the innate (inflammatory) over the acquired (antiviral) components of the immune system. We assessed inflammation using the ratio of inflammatory to antiviral cell types (ITACT Ratio). This approach provided a stronger test of evolutionary arguments regarding the effect of social stress on chronic inflammation than is the case with cytokine measures, and afforded an opportunity to replicate findings obtained utilizing mRNA. We used structural equation modeling and longitudinal data from a sample of 100 middle-age African American women to perform our analyses. Dominance of inflammatory over antiviral cell activity was associated with each of the eight illnesses included in our chronic illness measure. Both socioeconomic disadvantage and age were also associated with inflammatory dominance. Pursuant to the central focus of the study, the effects of socioeconomic adversity and age on increased illness were mediated by our measure of inflammatory dominance. The indirect effect of these variables through inflammatory cell profile was significant, with neither socioeconomic disadvantage nor age showing a significant association with illness once the impact of inflammatory cell profile was taken into account. First, the analysis provides preliminary validation of a new measure of inflammation that is calculated based on the ratio of inflammatory to antiviral white blood cells. Second, our results support the hypothesis that socioeconomic disadvantage and chronological age increase

  15. The six-spot-step test - a new method for monitoring walking ability in patients with chronic inflammatory polyneuropathy

    DEFF Research Database (Denmark)

    Kreutzfeldt, Melissa; Jensen, Henrik B; Ravnborg, Mads

    2017-01-01

    OBJECTIVE: To evaluate whether the Six-Spot-Step-Test (SSST) is more suitable for monitoring walking ability in patients with chronic inflammatory polyneuropathy than the Timed-25-Foot-Walking test (T25FW). METHOD: In the SSST, participants have to walk as quickly as possible across a field...... of effect size, standardized response means and relative efficiency. Both ambulation tests correlated moderately to PGIC. CONCLUSION: The SSST may be superior to the T25FW in terms of dynamic range, floor effect and responsiveness which makes the SSST a possible alternative for monitoring walking ability...

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

    Directory of Open Access Journals (Sweden)

    Kimberly T. Sibille

    2016-01-01

    Full Text Available 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.

  17. Obesity or Overweight, a Chronic Inflammatory Status in Male Reproductive System, Leads to Mice and Human Subfertility

    Directory of Open Access Journals (Sweden)

    Weimin Fan

    2018-01-01

    Full Text Available Obesity is frequently accompanied with chronic inflammation over the whole body and is always associated with symptoms that include those arising from metabolic and vascular alterations. On the other hand, the chronic inflammatory status in the male genital tract may directly impair spermatogenesis and is even associated with male subfertility. However, it is still unclear if the chronic inflammation induced by obesity damages spermatogenesis in the male genital tract. To address this question, we used a high fat diet (HFD induced obese mouse model and recruited obese patients from the clinic. We detected increased levels of tumor necrosis factor (TNF-α, interleukin-6 (IL-6, and NOD-like receptor family pyrin domain containing-3 (NLRP3 in genital tract tissues including testis, epididymis, seminal vesicle, prostate, and serum from obese mice. Meanwhile, the levels of immunoglobulin G (IgG and corticosterone were significantly higher than those in the control group in serum. Moreover, signal factors regulated by TNF-α, i.e., p38, nuclear factor-κB (NF-κB, Jun N-terminal kinase (JNK, extracellular signal-regulated kinase (ERK, and their phosphorylated status, and inflammasome protein NLRP3 were expressed at higher levels in the testis. For overweight and obese male patients, the increased levels of TNF-α and IL-6 were also observed in their seminal plasma. Furthermore, there was a positive correlation between the TNF-α and IL-6 levels and BMI whereas they were inversely correlated with the sperm concentration and motility. In conclusion, impairment of male fertility may stem from a chronic inflammatory status in the male genital tract of obese individuals.

  18. Osmotic demyelination syndrome with recent chemotherapy in normonatremic patient: A case report

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    Lee, Sungjae; Baek, Hye Jin; Jung, Hyun Kyung; Kim, Seon Jeong; Lee, Yedaun; Lee, Kwaghwi; Ryu, Ji Hwa; Kim, Hong Dae [Dept. of Radiology, Haeundae Paik Hospital, Inje University College of Medicine, Busan (Korea, Republic of)

    2014-11-15

    Osmotic demyelination syndrome (ODS), an acquired demyelinating condition of the central pons and/or other regions of the brain, is frequently associated with rapid correction of hyponatremia. There are several reports of ODS in other clinical setting such as malnutrition, alcoholism, transplantation, malignancy, and chronic debilitating illness. However, cases of ODS associated with chemotherapy have not been frequently reported. Here, we describe a case of ODS in a normonatremic patient recently underwent chemotherapy for colon cancer. The diagnosis was confirmed by MRI showing a typical T2 hyperintensity in the central pons. This case suggests that ODS is not always associated with hyponatremia and that ODS can have a favorable clinical and radiologic prognosis.

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

    Directory of Open Access Journals (Sweden)

    Chao Wang

    2015-01-01

    Full Text Available 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.

  20. Effects of prandial challenge on triglyceridemia, glycemia, and pro-inflammatory activity in persons with chronic paraplegia

    Science.gov (United States)

    Ellenbroek, Dennis; Kressler, Jochen; Cowan, Rachel E.; Burns, Patricia A.; Mendez, Armando J.; Nash, Mark S.

    2015-01-01

    Context/Objective Exaggerated postprandial lipemia has been reported after spinal cord injury (SCI). We examined metabolite and accompanying pro-inflammatory biomarker responses to repeat feeding of typical high-fat meals in individuals with chronic paraplegia. Design Descriptive trial. Methods Metabolites (triglycerides, glucose, and insulin) and inflammatory biomarkers (interleukin-6 and high-sensitivity C-reactive protein (hsCRP)) were measured under fasting conditions in 11 recreationally active individuals with chronic (>1 year) paraplegia. Subjects received high-fat meals at time point 0 and again at minute 240. Antecubital venous blood was obtained at time points −30 (fasting), 0 (first meal), 30, 60, 90, 120, 240 (second meal), 360, and 480 minutes. Correlations were examined among the study variables. Exploratory subgroup analysis was performed for subjects with levels of postprandial glucose greater than >200 mg/dl. Results Triglycerides showed a significant rise 4 hours after eating. Basal inflammatory markers were elevated, and did not undergo additional change during the testing. Additionally, subjects with excessive postprandial glucose responses showed higher hsCRP levels than those having typical glucose responses both for fasting (11.8 ± 6.5 vs. 2.9 ± 2.7 mg/l, P = 0.064) and postprandial (11.1 ± 4.9 vs. 3.7 ± 3.8 mg/l, P = 0.018) values. Conclusions Despite elevations in metabolic response markers, inflammatory markers did not change significantly after consumption of population-representative (i.e. hypercaloric) mixed-nutrient meals. Levels of fasting CRP in the high-risk range are consistent with other reports in persons with SCI and continue to pose concern for their cardiovascular disease risk. The possible association between postprandial metabolic responses and inflammatory states warrants further investigation to identify individual component risks for this secondary health hazard. PMID:24617559

  1. Microglial recruitment, activation, and proliferation in response to primary demyelination

    DEFF Research Database (Denmark)

    Remington, Leah T; Babcock, Alicia A; Zehntner, Simone P

    2007-01-01

    We have characterized the cellular response to demyelination/remyelination in the central nervous system using the toxin cuprizone, which causes reproducible demyelination in the corpus callosum. Microglia were distinguished from macrophages by relative CD45 expression (CD45(dim)) using flow cyto...

  2. Reduction of chronic abdominal pain in patients with inflammatory bowel disease through transcranial direct current stimulation: a randomized controlled trial.

    Science.gov (United States)

    Volz, Magdalena S; Farmer, Annabelle; Siegmund, Britta

    2016-02-01

    Inflammatory bowel disease (IBD) is frequently associated with chronic abdominal pain (CAP). Transcranial direct current stimulation (tDCS) has been proven to reduce chronic pain. This study aimed to investigate the effects of tDCS in patients with CAP due to IBD. This randomized, sham-controlled, double blind, parallel-designed study included 20 patients with either Crohn disease or ulcerative colitis with CAP (≥3/10 on the visual analog scale (VAS) in 3/6 months). Anodal or sham tDCS was applied over the primary motor cortex for 5 consecutive days (2 mA, 20 minutes). Assessments included VAS, pressure pain threshold, inflammatory markers, and questionnaires on quality of life, functional and disease specific symptoms (Irritable Bowel Syndrome-Severity Scoring System [IBS-SSS]), disease activity, and pain catastrophizing. Follow-up data were collected 1 week after the end of the stimulation. Statistical analyses were performed using analysis of variance and t tests. There was a significant reduction of abdominal pain in the anodal tDCS group compared with sham tDCS. This effect was evident in changes in VAS and pressure pain threshold on the left and right sides of the abdomen. In addition, 1 week after stimulation, pain reduction remained significantly decreased in the right side of the abdomen. There was also a significant reduction in scores on pain catastrophizing and on IBS-SSS when comparing both groups. Inflammatory markers and disease activity did not differ significantly between groups throughout the experiment. Transcranial direct current stimulation proved to be an effective and clinically relevant therapeutic strategy for CAP in IBD. The analgesic effects observed are unrelated to inflammation and disease activity, which emphasizes central pain mechanisms in CAP.

  3. Serial High-Resolution Computed Tomography Imaging in Patients with Wegener Granulomatosis: Differentiation Between Active Inflammatory and Chronic Fibrotic Lesions

    International Nuclear Information System (INIS)

    Lohrmann, C.; Uhl, M.; Schaefer, O.; Ghanem, N.; Kotter, E.; Langer, M.

    2005-01-01

    PURPOSE: To evaluate pulmonary pathologies in Wegener granulomatosis with sequential computed tomography (CT) in order to differentiate active inflammatory lesions from chronic fibrotic lesions. MATERIAL AND METHODS: Serial CT findings in 38 patients with Wegener granulomatosis were retrospectively analyzed (mean follow-up period, 21 months). The presence, extension, and distribution of the following findings were evaluated with CT: parenchymal nodules, masses, ground-glass attenuation, airspace consolidation, bronchial wall-thickening, bronchiectasis, linear areas of attenuation, pleural irregularities, pleural effusions, hilar and mediastinal lymphadenopathy. RESULTS: Observed in 92% of patients, nodules were the most common CT pathology. Areas of ground-glass attenuation, consolidation, masses of linear attenuation, and tracheal/bronchial wall-thickening were detected in 24%, 26%, 32%, 39%, and 68% of patients. At follow-up, the clearance of lesions was most consistent for areas of ground-glass attenuation (89%), masses (87%), and cavitated nodules (85%). In the follow-up scan, 58% of all nodules, 47% of pulmonary consolidations, and 66% of bronchial wall-thickening were completely resolved. Areas of bronchiectasis and septal/non-septal lines remained stable in 70% and 71% of patients. CONCLUSION: The majority of the lesions decreased or resolved completely with or without areas of linear attenuation. Ground-glass attenuation, cavitated nodules and masses appear to represent active inflammatory lesions. In most probability, areas of bronchiectasis and septal/non-septal lines more often represent chronic fibrotic changes rather than active inflammatory changes. In combination with clinical evaluation and bronchoscopy, CT assists in the assessment of disease activity

  4. Serial High-Resolution Computed Tomography Imaging in Patients with Wegener Granulomatosis: Differentiation Between Active Inflammatory and Chronic Fibrotic Lesions

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    Lohrmann, C.; Uhl, M.; Schaefer, O.; Ghanem, N.; Kotter, E.; Langer, M. [Univ. Hospital of Freiburg (Germany). Dept. of Radiology

    2005-08-01

    PURPOSE: To evaluate pulmonary pathologies in Wegener granulomatosis with sequential computed tomography (CT) in order to differentiate active inflammatory lesions from chronic fibrotic lesions. MATERIAL AND METHODS: Serial CT findings in 38 patients with Wegener granulomatosis were retrospectively analyzed (mean follow-up period, 21 months). The presence, extension, and distribution of the following findings were evaluated with CT: parenchymal nodules, masses, ground-glass attenuation, airspace consolidation, bronchial wall-thickening, bronchiectasis, linear areas of attenuation, pleural irregularities, pleural effusions, hilar and mediastinal lymphadenopathy. RESULTS: Observed in 92% of patients, nodules were the most common CT pathology. Areas of ground-glass attenuation, consolidation, masses of linear attenuation, and tracheal/bronchial wall-thickening were detected in 24%, 26%, 32%, 39%, and 68% of patients. At follow-up, the clearance of lesions was most consistent for areas of ground-glass attenuation (89%), masses (87%), and cavitated nodules (85%). In the follow-up scan, 58% of all nodules, 47% of pulmonary consolidations, and 66% of bronchial wall-thickening were completely resolved. Areas of bronchiectasis and septal/non-septal lines remained stable in 70% and 71% of patients. CONCLUSION: The majority of the lesions decreased or resolved completely with or without areas of linear attenuation. Ground-glass attenuation, cavitated nodules and masses appear to represent active inflammatory lesions. In most probability, areas of bronchiectasis and septal/non-septal lines more often represent chronic fibrotic changes rather than active inflammatory changes. In combination with clinical evaluation and bronchoscopy, CT assists in the assessment of disease activity.

  5. Experimental models of demyelination and remyelination.

    Science.gov (United States)

    Torre-Fuentes, L; Moreno-Jiménez, L; Pytel, V; Matías-Guiu, J A; Gómez-Pinedo, U; Matías-Guiu, J

    2017-08-29

    Experimental animal models constitute a useful tool to deepen our knowledge of central nervous system disorders. In the case of multiple sclerosis, however, there is no such specific model able to provide an overview of the disease; multiple models covering the different pathophysiological features of the disease are therefore necessary. We reviewed the different in vitro and in vivo experimental models used in multiple sclerosis research. Concerning in vitro models, we analysed cell cultures and slice models. As for in vivo models, we examined such models of autoimmunity and inflammation as experimental allergic encephalitis in different animals and virus-induced demyelinating diseases. Furthermore, we analysed models of demyelination and remyelination, including chemical lesions caused by cuprizone, lysolecithin, and ethidium bromide; zebrafish; and transgenic models. Experimental models provide a deeper understanding of the different pathogenic mechanisms involved in multiple sclerosis. Choosing one model or another depends on the specific aims of the study. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  6. Beneficial effects of minocycline on cuprizone induced cortical demyelination.

    Science.gov (United States)

    Skripuletz, Thomas; Miller, Elvira; Moharregh-Khiabani, Darius; Blank, Alexander; Pul, Refik; Gudi, Viktoria; Trebst, Corinna; Stangel, Martin

    2010-09-01

    In this study, we investigated the potential of minocycline to influence cuprizone induced demyelination in the grey and white matter. To induce demyelination C57BL/6 mice were fed with cuprizone for up to 6 weeks and were analysed at different timepoints (week 0, 4, 5, 6). Mice treated with minocycline had less demyelination of the cortex and corpus callosum compared with sham treated animals. In the cortex decreased numbers of activated and proliferating microglia were found after 6 weeks of cuprizone feeding, while there were no significant effects for microglial infiltration of the corpus callosum. In addition to the beneficial effects on demyelination, minocycline prevented from motor coordination disturbance as shown in the beam walking test. For astrogliosis and the numbers of OPC and oligodendrocytes no treatment effects were found. In summary, minocycline treatment diminished the course of demyelination in the grey and white matter and prevented disturbances in motor coordination.

  7. New-onset vitiligo and progression of pre-existing vitiligo during treatment with biological agents in chronic inflammatory diseases.

    Science.gov (United States)

    Méry-Bossard, L; Bagny, K; Chaby, G; Khemis, A; Maccari, F; Marotte, H; Perrot, J L; Reguiai, Z; Sigal, M L; Avenel-Audran, M; Boyé, T; Grasland, A; Gillard, J; Jullien, D; Toussirot, E

    2017-01-01

    The development of vitiligo during treatment with biological agents is an unusual event and only a few isolated cases have been reported. To describe the clinical characteristics and evolution of patients developing new-onset vitiligo following initiation of a biological agent for chronic inflammatory disease; and also to report the clinical course of pre-existing vitiligo under biological therapy. This nationwide multicentre, retrospective study, carried out between July 2013 and January 2015, describes the characteristics of a large series of 18 patients (psoriasis N = 8, inflammatory rheumatic diseases N = 8, ulcerative colitis N = 1, uveitis N = 1) who developed new-onset vitiligo while receiving a biological agent. TNFα inhibitors were the most common biological agent involved (13/18) while anti-IL-12/23 and anti-IL-17 agents or abatacept were less common (4/18 and 1/18 respectively). Mean duration of biological agent exposure before vitiligo onset was 13.9 ± 16.5 months. Outcome was favourable for most patients (15/17) while maintaining the biological agent. Data were also collected for 18 patients (psoriasis N = 5, inflammatory rheumatic diseases N = 10, inflammatory bowel diseases N = 2, SAPHO N = 1) who had pre-existing vitiligo when treatment with a biological agent started (TNFα inhibitors N = 15, ustekinumab N = 1, rituximab N = 1, tocilizumab N = 1). Vitiligo progressed in seven patients and was stable or improved in eight cases. Vitiligo may thus emerge and/or progress during treatment with various biological agents, mainly TNFα inhibitors and could be a new paradoxical skin reaction. De novo vitiligo displays a favourable outcome when maintaining the biological agent, whereas the prognosis seems worse in cases of pre-existing vitiligo. © 2016 European Academy of Dermatology and Venereology.

  8. Association of urinary phenolic compounds, inflammatory bowel disease and chronic diarrheal symptoms: Evidence from the National Health and Nutrition Examination Survey

    International Nuclear Information System (INIS)

    Silva, Punyanganie S. de; Yang, Xuan; Korzenik, Joshua R.; Goldman, Rose H.; Arheart, Kristopher L.; Caban-Martinez, Alberto J.

    2017-01-01

    Endocrine disruptors such as phenolic compounds and parabens may be involved in chronic non-infective disease. While products incorporating these compounds are extensively utilized in consumer and personal products, little is known about their effect on bowel health. Inflammatory bowel disease (IBD) - consisting of the diseases ulcerative colitis and Crohn's disease - and irritable bowel syndrome are common chronic non-infectious diarrheal diseases. Despite limited knowledge on the etiology of IBD, these diseases have increased prevalence in industrialized countries and cause significant impairment to quality of life. In the present study we examine relationships between urinary environmental phenolic compounds, chronic diarrhea and inflammatory bowel disease. Data was obtained from the 2005–2010 US National Health and Nutrition Examination Survey (NHANES) including demographics, lifestyle factors, self-reported health conditions, inflammatory markers and urinary phenolic chemical concentrations. Only participants with complete environmental phenols & parabens component were included in our analysis. Chronic diarrheal symptoms were determined by using the 2009–2010 NHANES questionnaire which included questions pertaining to bowel health. We utilized chronic bowel leakage symptoms as a surrogate marker for chronic diarrhea. The presence of IBD was also analyzed from 2009 to 2010 NHANES data, as a sub-analysis for arthropathy directly querying the presence or absence of IBD. Among the subset of 5218 American adults aged 20–80 years in the NHANES study period who completed environmental phenols & parabens component, 25.5% reported chronic diarrheal symptoms. Abnormal markers of inflammation were present in 2200 (42.2%) of respondents. For IBD, 19 individuals with arthropathy confirmed a diagnosis of ulcerative colitis, and 1 person confirmed a Crohn's diagnosis. After adjustment for demographics, inflammatory and subsample weighing; lower paraben

  9. Antibody-Mediated Rejection of the Heart in the Setting of Autoimmune Demyelinating Polyneuropathy: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Kathryn J. Lindley

    2012-01-01

    Full Text Available Background. Antibody-mediated rejection (AMR is caused by the production of donor-specific antibodies (DSA which lead to allograft injury in part via complement activation. The inflammatory demyelinating polyneuropathies (IDP are inflammatory disorders of the nervous system, involving both cellular and humoral immune mechanisms directed against myelin. Case Report. A 58-year-old man five years after heart transplant presented with progressive dyspnea, imbalance, dysphagia, and weakness. Nerve conduction studies and electromyogram were consistent with IDP. Plasmapheresis and high-dose steroids resulted in improvement in neurologic symptoms. Within two weeks, he was readmitted with anasarca and acute renal failure, requiring intravenous furosemide and inotropic support. Echocardiogram and right heart catheterization revealed reduced cardiac function and elevated filling pressures. DSA was positive against HLA DR53, and endomyocardial biopsy revealed grade 1R chronic inflammation, with strong capillary endothelial immunostaining for C4d. Plasmapheresis and intravenous immunoglobulin (IVIG were initiated. His anasarca and renal failure subsequently resolved, echocardiogram showed improved function off inotropes, and anti-DR53 MFI was reduced by 57%. Conclusions. This is an example of a single immune-mediated process causing concurrent IDP and AMR. The improvement in cardiac function and neurologic symptoms with plasmapheresis, IVIG, and high-dose steroids argues for a unifying antibody-mediated mechanism.

  10. Chronic oral infection with major periodontal bacteria Tannerella forsythia modulates systemic atherosclerosis risk factors and inflammatory markers.

    Science.gov (United States)

    Chukkapalli, Sasanka S; Rivera-Kweh, Mercedes F; Velsko, Irina M; Chen, Hao; Zheng, Donghang; Bhattacharyya, Indraneel; Gangula, Pandu R; Lucas, Alexandra R; Kesavalu, Lakshmyya

    2015-04-01

    Tannerella forsythia is a Gram-negative anaerobic organism that inhabits the subgingival cavity and initiates connective tissue destruction and alveolar bone resorption in periodontal disease (PD). PD is a chronic immunoinflammatory disease and has been linked to several systemic diseases including atherosclerosis. This study evaluated the effects of a chronic oral infection with T. forsythia ATCC 43037 on the induction of PD, inflammatory markers and atherosclerosis risk factors in hyperlipidemic ApoE(null) mice. Mice were orally infected for 12 and 24 weeks prior to euthanasia. Bacterial colonization of the oral cavity and bacteremia was confirmed via isolation of genomic DNA from oral plaque and tissues. Oral infection elicited significantly elevated levels of serum IgG and IgM antibodies and alveolar bone resorption compared to control mice. Tannerella forsythia-infected mice had increased serum amyloid A, and significantly reduced serum nitric oxide when compared to controls. Tannerella forsythia chronic infection also significantly increased serum lipoproteins suggesting altered cholesterol metabolism and potential for aortic inflammation. Despite enhanced acute phase reactants and altered lipid profiles, T. forsythia infection was associated with decreased aortic plaque. This study investigates the potential of a known periodontal bacterial pathogen found in atherosclerotic plaque in humans to accelerate atherosclerosis in hyperlipdemic mice. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  11. VIPER: Chronic Pain after Amputation: Inflammatory Mechanisms, Novel Analgesic Pathways, and Improved Patient Safety

    Science.gov (United States)

    2016-10-01

    Whitney U test for evaluating differences in inflammatory mediators between groups (Case vs. Control) and used nonparametric correlations (Spearman’s rho...responses to acute pain. PAIN 2008;140:135–144. [10] Gordon S, Martinez FO. Alternative activation of macrophages: mechanism and functions...Concentrations in Cases vs. Controls. Mediator Case (n=36) Median (Range) Control (n=40) Median (Range) Mann- Whitney U Test (p value) IFN

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

    Science.gov (United States)

    Inage, Kazuhide; 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

    2016-08-01

    Retrospective study. 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. 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. 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. 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 (ppain to chronic low back pain.

  13. Residential proximity to abandoned uranium mines and serum inflammatory potential in chronically exposed Navajo communities.

    Science.gov (United States)

    Harmon, Molly E; Lewis, Johnnye; Miller, Curtis; Hoover, Joseph; Ali, Abdul-Mehdi S; Shuey, Chris; Cajero, Miranda; Lucas, Selita; Zychowski, Katherine; Pacheco, Bernadette; Erdei, Esther; Ramone, Sandy; Nez, Teddy; Gonzales, Melissa; Campen, Matthew J

    2017-07-01

    Members of the Navajo Nation, who possess a high prevalence of cardiometabolic disease, reside near hundreds of local abandoned uranium mines (AUM), which contribute uranium, arsenic and other metals to the soil, water and air. We recently reported that hypertension is associated with mine waste exposures in this population. Inflammation is a major player in the development of numerous vascular ailments. Our previous work establishing that specific transcriptional responses of cultured endothelial cells treated with human serum can reveal relative circulating inflammatory potential in a manner responsive to pollutant exposures, providing a model to assess responses associated with exposure to these waste materials in this population. To investigate a potential link between exposures to AUM and serum inflammatory potential in affected communities, primary human coronary artery endothelial cells were treated for 4 h with serum provided by Navajo study participants (n=145). Endothelial transcriptional responses of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and chemokine ligand 2 (CCL2) were measured. These transcriptional responses were then linked to AUM exposure metrics, including surface area-weighted AUM proximity and estimated oral intake of metals. AUM proximity strongly predicted endothelial transcriptional responses to serum including CCL2, VCAM-1 and ICAM-1 (Puranium did not, even after controlling for all major effect modifiers. Inflammatory potential associated with proximity to AUMs, but not oral intake of specific metals, additionally suggests a role for inhalation exposure as a contributor to cardiovascular disease.

  14. Inflammatory Markers: C-Reactive Protein, Erythrocyte Sedimentation Rate, and Leukocyte Count in Vitamin D Deficient Patients with and without Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Ibrahim Yildirim

    2013-01-01

    Full Text Available Although some studies revealed a positive relationship between vitamin D3 deficiency and inflammatory markers, there have been also many studies that failed to find this relationship. The aim of this large scaled study is to determine the association between the level of plasma 25 hydroxy vitamin D3 [25-(OH D3] and inflammatory markers in the general population without chronic kidney disease (CKD and in patients with CKD. Participants with simultaneously measured inflammatory markers and 25-(OH D3 levels were retrospectively analyzed (n=1897. The incidence of all-cause inflammation infection, hospitalization, chronic renal failure, and vitamin B12 deficiency was evaluated. The medians of serum creatinine levels in subjects without renal failure were lower in 25-(OH D3 deficient group. Patients with CKD were more likely to have vitamin D3 deficiency compared with normal GFR. 25-(OH D3 levels were associated with a greater incidence of all-cause hospitalization, hypoalbuminemia, and vitamin B12 deficiency. However, there was no relationship between inflammatory markers and vitamin D3 levels. In 25-(OH D3 deficient patients, inflammatory markers can be related to other inflammatory and infectious status such as malnutrition and cachexia. We believed that there must be a relationship between vitamin deficiency and inflammatory markers due to other causes than low 25-(OH D3 status.

  15. Isolated Extrapontine Myelinolysis of Osmotic Demyelination Syndrome

    Directory of Open Access Journals (Sweden)

    Ömer Yılmaz

    2013-01-01

    Full Text Available The osmotic demyelination syndrome (ODS has been identified as a complication of the rapid correction of hyponatremia for decades (King and Rosner, 2010. However, in recent years, a variety of other medical conditions have been associated with the development of ODS, independent of changes in serum sodium which cause a rapid changes in osmolality of the interstitial (extracellular compartment of the brain leading to dehydration of energy-depleted cells with subsequent axonal damage that occurs in characteristic areas (King and Rosner, 2010. Slow correction of the serum sodium concentration and additional administration of corticosteroids seems to be a major prevention step in ODS patients. In the current report we aimed to share a rare case which we observed in our clinic.

  16. Gratitude uniquely predicts lower depression in chronic illness populations: A longitudinal study of inflammatory bowel disease and arthritis.

    Science.gov (United States)

    Sirois, Fuschia M; Wood, Alex M

    2017-02-01

    Although gratitude has been identified as a key clinically relevant trait for improving well-being, it is understudied within medical populations. The current study addressed this gap and extended previous and limited cross-sectional research by examining the longitudinal associations of gratitude to depression in 2 chronic illness samples, arthritis and inflammatory bowel disease (IBD). Two chronic illness samples, arthritis (N = 423) and IBD (N = 427), completed online surveys at Time 1 (T1). One hundred sixty-three people with arthritis and 144 people with IBD completed the 6-month follow-up survey (T2). Depression, gratitude, illness cognitions, perceived stress, social support, and disease-related variables were assessed at T1 and T2. At T2, 57.2% of the arthritis sample and 53.4% of the IBD sample met the cut off scores for significant depression. T1 gratitude was negatively associated with depressive symptoms at T1 and T2 in both samples (rs from -.43 to -.50). Regression analyses revealed that T1 gratitude remained a significant and unique predictor of lower T2 depression after controlling for T1 depression, relevant demographic variables, illness cognitions, changes in illness-relevant variables, and another positive psychological construct, thriving, in both samples. As the first investigation of the longitudinal associations of gratitude to psychological well-being in the context of chronic illness, the current study provides important evidence for the relevance of gratitude for health-related clinical populations. Further intervention-based research is warranted to more fully understand the potential benefits of gratitude for adjustment to chronic illness. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  17. . Chronic kidney disease in patients with chronic back pain taking non-steroidal anti-inflammatory drugs

    Directory of Open Access Journals (Sweden)

    Gaydukova I.Z.

    2016-03-01

    in patients with ax-SpA, DDS and controls were comparable. The activity of pain was evaluated according to the accepted recommendations. The index of NSAID intake as calculated for the preceding year. Results. GFR in patients with ax-SpAwas 87,0 [77,25; 102,0] ml/min/1,73 m2, 11 (18% patients showed a reduction in GFR of less than 60 ml/ min/1,73m2. In patients with DDS GFR was 87,5 [65,5; 97,0] ml/min / 1,73 m 2 (p=0,27, decreased GFR of less than 60 ml/min / 1,73 m2 was detected in 3 (15% patients. The ratio of albumin / creatinine urine in patients with ax-SpA was 35,8 [25,46; 43,4] mg/g, in patients DDS —207,1 [91,66; 244,59] mg/g (p<0,0001, in healthy individuals —25,45 [17,34; 33,65] mg/g. Conclusions. Patients with chronic back pain taking NSAIDs for a long time have revealed GFR, comparable with healthy people, and increased urine albumin. Patients with degenerative diseases of the spine have a greater index of albumin in urine than patients with ax-SpA.

  18. Comparison of fenspiride with beclomethasone as adjunctive anti-inflammatory treatment in patients with chronic obstructive pulmonary disease.

    Science.gov (United States)

    Shmelev, E I; Kunicina, Yu L

    2006-01-01

    This study aimed to compare the clinical efficacy of two anti-inflammatory medications (fenspiride and inhaled beclomethasone [beclomethasone dipropionate]) in patients with stable chronic obstructive pulmonary disease (COPD) over 6 months. DESIGN, METHODS AND PATIENTS: This was a randomised comparison of 58 patients with COPD, divided into five treatment groups: fenspiride (stages 1 and 2), beclomethasone (stage 2), and two control groups (stages 1 and 2). In addition, 64 patients with exacerbations of COPD were evaluated over a 2-week treatment period during which they received either fenspiride or prednisolone. Clinical signs and symptoms of COPD were evaluated every 2 months (aggregated numerical index of signs and symptoms), as were lung function tests (forced vital capacity [FVC], forced expiratory volume in 1 second [FEV1], FEV1/FVC) and a 6-minute walking test. Statistically significant reductions in all evaluated COPD signs and symptoms were achieved with fenspiride in stage 1 COPD. Fenspiride therapy significantly reduced the indices of sputum parameters (8-fold decrease), incidence of dry rales (6-fold decrease), dyspnoea (4-fold decrease) and cough (2.5-fold decrease). In comparison with beclomethasone, fenspiride was superior in stage 2 COPD. In patients with stage 2 COPD, reductions were less marked, but remained significantly superior in the fenspiride group in comparison with the beclomethasone group and the control groups. In patients with exacerbations of COPD, fenspiride had equivalent efficacy to that of systemic corticosteroids. Anti-inflammatory therapy with fenspiride in addition to bronchodilators significantly improved clinical signs and symptoms, external respiratory function tests and physical activity tests in patients with stage 1 COPD. Adjunctive fenspiride therapy was superior to inhaled beclomethasone in stage 2 COPD. Anti-inflammatory therapy in COPD may be more effective at an early stage of this disease.

  19. The significance and predictive value of free light chains in the urine of patients with chronic inflammatory rheumatic disease.

    Science.gov (United States)

    Bramlage, Carsten Paul; Froelich, Britta; Wallbach, Manuel; Minguet, Joan; Grupp, Clemens; Deutsch, Cornelia; Bramlage, Peter; Koziolek, Michael; Müller, Gerhard Anton

    2016-12-01

    In patients with rheumatic diseases, reliable markers for determining disease activity are scarce. One potential parameter is the level of immunoglobulin free light chains (FLCs), which is known to be elevated in the blood of patients with certain rheumatic diseases. Few studies have quantified FLCs in urine, a convenient source of test sample, in patients with different rheumatic diseases. We carried out a retrospective analysis of patients with rheumatic disease attending the University hospital of Goettingen, Germany. Subjects were included if they had urine levels of both κ and λ FLCs available and did not have myeloma. Data regarding systemic inflammation and kidney function were recorded, and FLC levels were correlated with inflammatory markers. Of the 382 patients with rheumatic disease, 40.1 % had chronic polyarthritis, 21.2 % connective tissue disease, 18.6 % spondyloarthritis and 15.7 % vasculitis. Elevated levels of κ FLCs were found for 84 % of patients and elevated λ for 52.7 %. For the patients with rheumatoid arthritis, FLCs correlated with C-reactive protein (κ, r = 0.368, p rheumatic disease, but not in κ/λ ratio. The correlation between FLCs and inflammatory markers in patients with rheumatoid arthritis demonstrates their potential for predicting disease activity.

  20. Fecal Microbiota and Metabolome in a Mouse Model of Spontaneous Chronic Colitis: Relevance to Human Inflammatory Bowel Disease.

    Science.gov (United States)

    Robinson, Ainsley M; Gondalia, Shakuntla V; Karpe, Avinash V; Eri, Rajaraman; Beale, David J; Morrison, Paul D; Palombo, Enzo A; Nurgali, Kulmira

    2016-12-01

    Dysbiosis of the gut microbiota may be involved in the pathogenesis of inflammatory bowel disease (IBD). However, the mechanisms underlying the role of the intestinal microbiome and metabolome in IBD onset and its alteration during active treatment and recovery remain unknown. Animal models of chronic intestinal inflammation with similar microbial and metabolomic profiles would enable investigation of these mechanisms and development of more effective treatments. Recently, the Winnie mouse model of colitis closely representing the clinical symptoms and characteristics of human IBD has been developed. In this study, we have analyzed fecal microbial and metabolomic profiles in Winnie mice and discussed their relevance to human IBD. The 16S rRNA gene was sequenced from fecal DNA of Winnie and C57BL/6 mice to define operational taxonomic units at ≥97% similarity threshold. Metabolomic profiling of the same fecal samples was performed by gas chromatography-mass spectrometry. Composition of the dominant microbiota was disturbed, and prominent differences were evident at all levels of the intestinal microbiome in fecal samples from Winnie mice, similar to observations in patients with IBD. Metabolomic profiling revealed that chronic colitis in Winnie mice upregulated production of metabolites and altered several metabolic pathways, mostly affecting amino acid synthesis and breakdown of monosaccharides to short chain fatty acids. Significant dysbiosis in the Winnie mouse gut replicates many changes observed in patients with IBD. These results provide justification for the suitability of this model to investigate mechanisms underlying the role of intestinal microbiota and metabolome in the pathophysiology of IBD.

  1. Co-Designing a Collaborative Chronic Care Network (C3N) for Inflammatory Bowel Disease: Development of Methods

    Science.gov (United States)

    Dellal, George; Peterson, Laura E; Provost, Lloyd; Gloor, Peter A; Fore, David Livingstone; Margolis, Peter A

    2018-01-01

    Background Our health care system fails to deliver necessary results, and incremental system improvements will not deliver needed change. Learning health systems (LHSs) are seen as a means to accelerate outcomes, improve care delivery, and further clinical research; yet, few such systems exist. We describe the process of codesigning, with all relevant stakeholders, an approach for creating a collaborative chronic care network (C3N), a peer-produced networked LHS. Objective The objective of this study was to report the methods used, with a diverse group of stakeholders, to translate the idea of a C3N to a set of actionable next steps. Methods The setting was ImproveCareNow, an improvement network for pediatric inflammatory bowel disease. In collaboration with patients and families, clinicians, researchers, social scientists, technologists, and designers, C3N leaders used a modified idealized design process to develop a design for a C3N. Results Over 100 people participated in the design process that resulted in (1) an overall concept design for the ImproveCareNow C3N, (2) a logic model for bringing about this system, and (3) 13 potential innovations likely to increase awareness and agency, make it easier to collect and share information, and to enhance collaboration that could be tested collectively to bring about the C3N. Conclusions We demonstrate methods that resulted in a design that has the potential to transform the chronic care system into an LHS. PMID:29472173

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

    Directory of Open Access Journals (Sweden)

    Luigi Nibali

    2014-02-01

    Full Text Available 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.

  3. Diagnostic evaluation of chronic inflammatory intestinal diseases in children and adolescents: MRI with true-FISP as new gold standard?

    International Nuclear Information System (INIS)

    Hohl, C.; Haage, P.; Krombach, G.A.; Schmidt, T.; Guenther, R.W.; Staatz, G.; Ahaus, M.

    2005-01-01

    Purpose: to evaluate the impact of magnetic resonance imaging (MRI) with use of True-FISP sequences in the evaluation of inflammatory bowel-wall changes in children and adolescents with Crohn's disease. Furthermore, the diagnostic procedure in children and adolescents with chronic inflammatory bowel disease (IBD) will be discussed in light of the relevant literature. Material and methods: twenty-four children and adolescents aged between 7 and 21 years with suspected or known IBD underwent MRI on a 1.5T-scanner (Philips ACS-NT, Best, Netherlands). One hour after 11 of a 2.5% mannitol solution was given orally, MR imaging was performed using coronal HASTE-M2D, coronal fat-suppressed T2-TSE, axial dynamic T1-weighted GE-sequences before and after i.v.-contrast material injection (0.1 mmol/kg Gd-DTPA) and using a 2D-balanced-FFE-sequence (True-FISP) before and after i.v.-contrast material injection in coronal and axial planes. The MR-images were correlated with endoscopy and the clinical findings. In 14 patients, a recently performed conventional radiographic enteroclysis was available. Each performed MRI sequence was evaluated by three experienced radiologists regarding the sensitivity and specificity of each sequence in the detection of inflammatory bowel wall changes. In addition, the image quality was assessed regarding the different tissue contrasts and the susceptibility to artifacts. The distension of the bowel wall and the patients' acceptance of the MRI examination were recorded. Results: with a sensitivity in detecting inflammatory small bowel changes of 93.3% (axial pre-contrast, coronal post-contrast) and 100% (axial post-contrast, coronal pre-contrast), the True-FISP outnumbers the other performed sequences (T1 = 80%, HASTE = 13.3% and T2-TSE = 53.3%). The difference between True-FISP and contrast-enhanced T1 was not statistically significant, whereas the difference between True-FISP and HASTE and T2-TSE, respectively. (orig.)

  4. Effects of the PPAR-β agonist GW501516 in an in vitro model of brain inflammation and antibody-induced demyelination

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    Honegger Paul

    2009-05-01

    Full Text Available Abstract Background Brain inflammation plays a central role in numerous brain pathologies, including multiple sclerosis (MS. Microglial cells and astrocytes are the effector cells of neuroinflammation. They can be activated also by agents such as interferon-γ (IFN-γ and lipopolysaccharide (LPS. Peroxisome proliferator-associated receptor (PPAR pathways are involved in the control of the inflammatory processes, and PPAR-β seems to play an important role in the regulation of central inflammation. In addition, PPAR-β agonists were shown to have trophic effects on oligodendrocytes in vitro, and to confer partial protection in experimental autoimmune encephalomyelitis (EAE, an animal model of MS. In the present work, a three-dimensional brain cell culture system was used as in vitro model to study antibody-induced demyelination and inflammatory responses. GW 501516, a specific PPAR-β agonist, was examined for its capacity to protect from antibody-mediated demyelination and to prevent inflammatory responses induced by IFN-γ and LPS. Methods Aggregating brain cells cultures were prepared from embryonal rat brain, and used to study the inflammatory responses triggered by IFN-γ and LPS and by antibody-mediated demyelination induced by antibodies directed against myelin-oligodendrocyte glycoprotein (MOG. The effects of GW 501516 on cellular responses were characterized by the quantification of the mRNA expression of tumor necrosis factor-α (TNF-α, interleukin-6 (IL-6, inducible NO synthase (i-NOS, PPAR-β, PPAR-γ, glial fibrillary acidic protein (GFAP, myelin basic protein (MBP, and high molecular weight neurofilament protein (NF-H. GFAP expression was also examined by immunocytochemistry, and microglial cells were visualized by isolectin B4 (IB4 and ED1 labeling. Results GW 501516 decreased the IFN-γ-induced up-regulation of TNF-α and iNOS in accord with the proposed anti-inflammatory effects of this PPAR-β agonist. However, it increased IL

  5. Nociceptive and inflammatory mediator upregulation in a mouse model of chronic prostatitis.

    Science.gov (United States)

    Schwartz, Erica S; Xie, Amy; La, Jun-Ho; Gebhart, G F

    2015-08-01

    Chronic nonbacterial prostatitis, characterized by genitourinary pain in the pelvic region in the absence of an identifiable cause, is common in adult males. Surprisingly, the sensory innervation of the prostate and mediators that sensitize its innervation have received little attention. We thus characterized a mouse model of chronic prostatitis, focusing on the prostate innervation and how organ inflammation affects gene expression of putative nociceptive markers in prostate afferent somata in dorsal root ganglia (DRG) and mediators in the prostate. Retrograde tracing (fast blue) from the prostate revealed that thoracolumbar and lumbosacral DRG are the principal sources of somata of prostate afferents. Nociceptive markers (eg, transient receptor potential, TREK, and P2X channels) were upregulated in fast blue-labeled thoracolumbar and lumbosacral somata for up to four weeks after inflaming the prostate (intraprostate injection of zymosan). Prostatic inflammation was evident histologically, by monocyte infiltration and a significant increase in mast cell tryptase activity 14, 21, and 28 days after zymosan injection. Interleukin 10 and NGF were also significantly upregulated in the prostate throughout the 4 weeks of inflammation. Open-field pain-related behaviors (eg, rearing) were unchanged in prostate-inflamed mice, suggesting the absence of ongoing nociception, but withdrawal thresholds to lower abdominal pressure were significantly reduced. The increases in IL-10, mast cell tryptase, and NGF in the inflamed prostate were cotemporaneous with reduced thresholds to probing of the abdomen and upregulation of nociceptive markers in DRG somata innervating the prostate. The results provide insight and direction for the study of mechanisms underlying pain in chronic prostatitis.

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

    Science.gov (United States)

    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.

  7. Spectroscopic magnetic resonance imaging of a tumefactive demyelinating lesion

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    Law, M.; Meltzer, D.E.; Cha, S. [MRI Department, Department of Radiology, New York University Medical Center, Schwartz Building, Basement HCC, 530 First Avenue, New York, NY 10016 (United States)

    2002-12-01

    Tumefactive demyelinating lesions can present with features similar, clinically and radiologically, to those of brain tumours. Proton MR spectroscopy has been increasingly used to characterize intracranial pathology. As the underlying pathophysiology of neoplasms is different from that of demyelinating disease, one may expect the metabolic composition of neoplasms to be significantly different from that of demyelinating lesions. We report a 49-year-old woman in whom the neurologic and radiologic findings were highly suggestive of a high-grade brain tumor, and the spectroscopic features were sufficiently similar to that of a tumor to convince the neurosurgeon to operate. This case emphasizes the need for caution when confronted with a patient who presents with a differential diagnosis of demyelinating lesion versus neoplasm. (orig.)

  8. Open-ring enhancement sign in diagnosing demyelinating pseudotumor

    International Nuclear Information System (INIS)

    Fang Liting; Wang Zhiping; Wang Linyou

    2010-01-01

    Objective: To describe open-ring enhancement sign on MRI of demyelinating pseudotumor. Methods: Contrast-enhanced MRI of histologically confirmed demyelinating pseudotumors (14 patients) and astrocytomas (21) was reviewed. Results: Of the 14 cases of demyelinating pseudotumor, open-ring enhancement pattern was observed in 6; closed ring enhancement in 2; nodular enhancement in 3; patchy enhancement in 1; slight enhancement in 1; and no enhancement in 1. Of the 21 cases of astrocytoma, there was complete ring or lace-like enhancement in 13, no contrast enhancement in 6, patchy enhancement in 2, and none with open-ring enhancement pattern. Conclusion: Open-ring enhancement is a valuable sign in differential diagnosis between demyelinating pseudotumor and astrocytoma. (authors)

  9. Resveratrol exerts anti-inflammatory and neuroprotective effects to prevent memory deficits in rats exposed to chronic unpredictable mild stress.

    Science.gov (United States)

    Yazir, Yusufhan; Utkan, Tijen; Gacar, Nejat; Aricioglu, Feyza

    2015-01-01

    A number of studies have recently focused on the neuroprotective and anti-inflammatory effects of resveratrol. In prior studies, we described its beneficial effects on scopolamine-induced learning deficits in rats. The aim of this study was to investigate the effects of resveratrol on emotional and spatial cognitive functions, neurotropic factor expression, and plasma levels of proinflammatory cytokines in rats exposed to chronic unpredictable mild stress (CUMS), which is known to induce cognitive deficits. Resveratrol (5 or 20mg/kg) was administered intraperitoneally for 35 days. Rats in the CUMS group and in the 5mg/kg resveratrol+CUMS group performed poorly in tasks designed to assess emotional and spatial learning and memory. The 20mg/kg resveratrol+CUMS group showed improved performance compared to the CUMS group. In addition, the CUMS procedure induced lower expression of brain-derived neurotrophic factor and c-Fos in hippocampal CA1 and CA3 and in the amygdala of stressed rats. These effects were reversed by chronic administration of resveratrol (20mg/kg). In addition, plasma levels of tumor necrosis factor-alpha and interleukin-1 beta were increased by CUMS, but were restored to normal by resveratrol. These results indicate that resveratrol significantly attenuates the deficits in emotional learning and spatial memory seen in chronically stressed rats. These effects may be related to resveratrol-mediated changes in neurotrophin factor expression in hippocampus and in levels of proinflammatory cytokines in circulation. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Regulatory effect of triiodothyronine on brain myelination and astrogliosis after cuprizone-induced demyelination in mice.

    Science.gov (United States)

    Zendedel, Adib; Kashani, Iraj Ragerdi; Azimzadeh, Maryam; Pasbakhsh, Parichehr; Omidi, Negar; Golestani, Abolfazl; Beyer, Cordian; Clarner, Tim

    2016-04-01

    Chronic demyelination and plaque formation in multiple sclerosis is accompanied by persisting astrogliosis, negatively influencing central nervous system recovery and remyelination. Triiodothyronin (T3) is thought to enhance remyelination in the adult brain by the induction of oligodendrocyte maturation. We investigated additional astrocyte-mediated mechanisms by which T3 might promote remyelination in chronically demyelinated lesions using the cuprizone mouse model. C57BL/6 mice were fed cuprizone for 12 weeks to induce lesions with an impaired remyelination capacity. While the expression of oligodenrocyte progenitor markers, i.e., platelet derived growth factor-α receptor was not affected by T3 administration, myelination status, myelin protein expression as well as total and adult oligodendrocyte numbers were markedly increased compared to cuprizone treated controls. In addition to these effects on oligodendrocyte numbers and function, astrogliosis but not microgliosis was ameliorated by T3 administration. Intermediate filament proteins vimentin and nestin as well as the extracellular matrix component tenascin C were significantly reduced after T3 exposure, indicating additional effects of T3 on astrocytes and astrogliosis. Our data clearly indicate that T3 promotes remyelination in chronic lesions by both enhancing oligodendrocyte maturation and attenuating astrogliosis.

  11. Acute Demyelinating Disease after Oral Therapy with Herbal Extracts

    Directory of Open Access Journals (Sweden)

    Alex Kostianovsky

    2011-06-01

    Full Text Available Central nervous system demyelinating processes such as multiple sclerosis and acute disseminated encephalomyelitis constitute a group of diseases not completely understood in their physiopathology. Environmental and toxic insults are thought to play a role in priming autoimmunity. The aim of the present report is to describe a case of acute demyelinating disease with fatal outcome occurring 15 days after oral exposure to herbal extracts.

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

    Science.gov (United States)

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

    2011-10-01

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

  13. Dynamic impact of brief electrical nerve stimulation on the neural immune axis-polarization of macrophages toward a pro-repair phenotype in demyelinated peripheral nerve.

    Science.gov (United States)

    McLean, Nikki A; Verge, Valerie M K

    2016-09-01

    Demyelinating peripheral nerves are infiltrated by cells of the monocyte lineage, including macrophages, which are highly plastic, existing on a continuum from pro-inflammatory M1 to pro-repair M2 phenotypic states. Whether one can therapeutically manipulate demyelinated peripheral nerves to promote a pro-repair M2 phenotype remains to be elucidated. We previously identified brief electrical nerve stimulation (ES) as therapeutically beneficial for remyelination, benefits which include accelerated clearance of macrophages, making us theorize that ES alters the local immune response. Thus, the impact of ES on the immune microenvironment in the zone of demyelination was examined. Adult male rat tibial nerves were focally demyelinated via 1% lysophosphatidyl choline (LPC) injection. Five days later, half underwent 1 hour 20 Hz sciatic nerve ES proximal to the LPC injection site. ES had a remarkable and significant impact, shifting the macrophage phenotype from predominantly pro-inflammatory/M1 toward a predominantly pro-repair/M2 one, as evidenced by an increased incidence of expression of M2-associated phenotypic markers in identified macrophages and a decrease in M1-associated marker expression. This was discernible at 3 days post-ES (8 days post-LPC) and continued at the 5 day post-ES (10 days post-LPC) time point examined. ES also affected chemokine (C-C motif) ligand 2 (CCL2; aka MCP-1) expression in a manner that correlated with increases and decreases in macrophage numbers observed in the demyelination zone. The data establish that briefly increasing neuronal activity favorably alters the immune microenvironment in demyelinated nerve, rapidly polarizing macrophages toward a pro-repair phenotype, a beneficial therapeutic concept that may extend to other pathologies. GLIA 2016;64:1546-1561. © 2016 Wiley Periodicals, Inc.

  14. Influence of type 2 diabetes on local production of inflammatory molecules in adults with and without chronic periodontitis: a cross-sectional study.

    Science.gov (United States)

    Mohamed, Hasaan G; Idris, Shaza B; Ahmed, Mutaz F; Åstrøm, Anne N; Mustafa, Kamal; Ibrahim, Salah O; Mustafa, Manal

    2015-07-27

    Pathological changes in periodontal tissues are mediated by the interaction between microorganisms and the host immune-inflammatory response. Hyperglycemia may interfere with this process. The aim of this study was to compare the levels of 27 inflammatory molecules in the gingival crevicular fluid (GCF) of patients with type 2 diabetes, with and without chronic periodontitis, and of chronic periodontitis subjects without diabetes. A putative correlation between glycated haemoglobin (HbA1c) and levels of the inflammatory molecules was also investigated. The study population comprised a total of 108 individuals, stratified into: 54 with type 2 diabetes and chronic periodontitis (DM + CP), 30 with chronic periodontitis (CP) and 24 with type 2 diabetes (DM). Participants were interviewed with the aid of structured questionnaire. Periodontal parameters (dental plaque, bleeding on probing and periodontal pocket depth) were recorded. The GCF levels of the 27 inflammatory molecules were measured using multiplex micro-bead immunoassay. A glycated haemoglobin (HbA1c) test was performed for patients with diabetes by boronate affinity chromatography. After adjustment for potential confounders, the DM + CP group had higher levels of IL-8 and MIP-1β, and lower levels of TNF-α, IL-4, INF-γ, RANTES and IL-7 compared to the CP group. Moreover, the DM + CP group had lower levels of IL-6, IL-7 and G-CSF compared to the DM group. The DM group had higher levels of IL-10, VEGF, and G-CSF compared to the CP group. The levels of MIP-1α and FGF were lower in diabetes patients (regardless of their periodontal status) than in chronic periodontitis subjects without diabetes. Diabetes patients (DM + CP and DM) had higher Th-2/Th-1 ratio compared to the CP group. HbA1c correlated positively with the pro-inflammatory cytokines (Pearson correlation coefficient = 0.27, P value: 0.02). Type 2 diabetes and chronic periodontitis may influence the GCF levels of inflammatory molecules

  15. Non-steroidal anti-inflammatory drugs (NSAIDs) for chronic non-cancer pain in children and adolescents.

    Science.gov (United States)

    Eccleston, Christopher; Cooper, Tess E; Fisher, Emma; Anderson, Brian; Wilkinson, Nick Mr

    2017-08-02

    Pain is a common feature of childhood and adolescence around the world, and for many young people, that pain is chronic. The World Health Organization guidelines for pharmacological treatments for children's persisting pain acknowledge that pain in children is a major public health concern of high significance in most parts of the world. While in the past pain was largely dismissed and was frequently left untreated, views on children's pain have changed over time, and relief of pain is now seen as important.We designed a suite of seven reviews on chronic non-cancer pain and cancer pain (looking at antidepressants, antiepileptic drugs, non-steroidal anti-inflammatory drugs, opioids, and paracetamol) in order to review the evidence for children's pain utilising pharmacological interventions.As the leading cause of morbidity in the world today, chronic disease (and its associated pain) is a major health concern. Chronic pain (that is pain lasting three months or longer) can arise in the paediatric population in a variety of pathophysiological classifications (nociceptive, neuropathic, or idiopathic) from genetic conditions, nerve damage pain, chronic musculoskeletal pain, and chronic abdominal pain, as well as for other unknown reasons.Non-steroidal anti-inflammatory drugs (NSAIDs) are used to treat pain, reduce fever, and for their anti-inflammation properties. They are commonly used within paediatric pain management. Non-steroidal anti-inflammatory drugs are currently licensed for use in Western countries, however they are not approved for infants under three months old. The main adverse effects include renal impairment and gastrointestinal issues. Common side effects in children include diarrhoea, headache, nausea, constipation, rash, dizziness, and abdominal pain. To assess the analgesic efficacy and adverse events of NSAIDs used to treat chronic non-cancer pain in children and adolescents aged between birth and 17 years, in any setting. We searched the Cochrane

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

    Science.gov (United States)

    Stringer, Elizabeth Ann; Baker, Katharine Susanne; Carroll, Ian R; Montoya, Jose G; Chu, Lily; Maecker, Holden T; Younger, Jarred W

    2013-04-09

    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. 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. 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. Our results support the role of cytokines in the pathophysiology of CFS.

  17. Biochemical parameters as monitoring markers of the inflammatory reaction by patients with chronic obstructive pulmonary disease (COPD)

    Science.gov (United States)

    Lenártová, Petra; Kopčeková, Jana; Gažarová, Martina; Mrázová, Jana; Wyka, Joanna

    Chronic obstructive pulmonary disease (COPD) is an airway inflammatory disease caused by inhalation of toxic particles, mainly cigarette smoking, and now is accepted as a disease associated with systemic characteristics. The aim of this work was to investigate and compare selected biochemical parameters in patients with and without COPD. Observation group consisted of clinically stable patients with COPD (n = 60). The control group was healthy persons from the general population, without COPD, who were divided into two subgroups – smokers (n = 30) and non-smokers (n = 30). Laboratory parameters were investigated by automated clinical chemistry analyzer LISA 200th. Albumin in our measurements showed an average value of 39.55 g.l-1 in the patient population; 38.89 g.l-1 in smokers and in non-smokers group 44.65 g.l-1. The average value of pre-albumin in the group of patients was 0.28 ± 0.28 g.l-1 and 0.30 ± 0.04 g.l-1 in smokers group. The average value of the orosomucoid in patients was about 1.11 ± 0.90 mg.ml-1. In the group of smokers, the mean value of orosomucoid was 0.60 ± 0.13 mg.ml-1. The level of C-reactive protein (CRP) in the patient group reached an average value of 15.31 ± 22.04 mg.l-1, in the group of smokers was 5.18 ± 4.58 mg. l-1. Prognostic inflammatory and nutritional index (PINI) in the group of patients showed a mean value of 4.65 ± 10.77 and 0.026 ± 0.025 in smokers. The results of this work show, that the values of index PINI in COPD patients are significantly higher than in smokers (P COPD.

  18. Accumulation of Extracellular Matrix in Advanced Lesions of Canine Distemper Demyelinating Encephalitis.

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    Seehusen, Frauke; Al-Azreg, Seham A; Raddatz, Barbara B; Haist, Verena; Puff, Christina; Spitzbarth, Ingo; Ulrich, Reiner; Baumgärtner, Wolfgang

    2016-01-01

    In demyelinating diseases, changes in the quality and quantity of the extracellular matrix (ECM) may contribute to demyelination and failure of myelin repair and axonal sprouting, especially in chronic lesions. To characterize changes in the ECM in canine distemper demyelinating leukoencephalitis (DL), histochemical and immunohistochemical investigations of formalin-fixed paraffin-embedded cerebella using azan, picrosirius red and Gomori`s silver stain as well as antibodies directed against aggrecan, type I and IV collagen, fibronectin, laminin and phosphacan showed alterations of the ECM in CDV-infected dogs. A significantly increased amount of aggrecan was detected in early and late white matter lesions. In addition, the positive signal for collagens I and IV as well as fibronectin was significantly increased in late lesions. Conversely, the expression of phosphacan was significantly decreased in early and more pronounced in late lesions compared to controls. Furthermore, a set of genes involved in ECM was extracted from a publically available microarray data set and was analyzed for differential gene expression. Gene expression of ECM molecules, their biosynthesis pathways, and pro-fibrotic factors was mildly up-regulated whereas expression of matrix remodeling enzymes was up-regulated to a relatively higher extent. Summarized, the observed findings indicate that changes in the quality and content of ECM molecules represent important, mainly post-transcriptional features in advanced canine distemper lesions. Considering the insufficiency of morphological regeneration in chronic distemper lesions, the accumulated ECM seems to play a crucial role upon regenerative processes and may explain the relatively small regenerative potential in late stages of this disease.

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

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    Roya Hemayati

    2015-01-01

    Full Text Available 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.

  20. Differential local tissue permissiveness influences the final fate of GPR17-expressing oligodendrocyte precursors in two distinct models of demyelination.

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    Coppolino, Giusy T; Marangon, Davide; Negri, Camilla; Menichetti, Gianluca; Fumagalli, Marta; Gelosa, Paolo; Dimou, Leda; Furlan, Roberto; Lecca, Davide; Abbracchio, Maria P

    2018-05-01

    Promoting remyelination is recognized as a novel strategy to foster repair in neurodegenerative demyelinating diseases, such as multiple sclerosis. In this respect, the receptor GPR17, recently emerged as a new target for remyelination, is expressed by early oligodendrocyte precursors (OPCs) and after a certain differentiation stage it has to be downregulated to allow progression to mature myelinating oligodendrocytes. Here, we took advantage of the first inducible GPR17 reporter mouse line (GPR17-iCreER T2 xCAG-eGFP mice) allowing to follow the final fate of GPR17 + cells by tamoxifen-induced GFP-labeling to unveil the destiny of these cells in two demyelination models: experimental autoimmune encephalomyelitis (EAE), characterized by marked immune cell activation and inflammation, and cuprizone induced demyelination, where myelin dysfunction is achieved by a toxic insult. In both models, demyelination induced a strong increase of fluorescent GFP + cells at damaged areas. However, only in the cuprizone model reacting GFP + cells terminally differentiated to mature oligodendrocytes, thus contributing to remyelination. In EAE, GFP + cells were blocked at immature stages and never became myelinating oligodendrocytes. We suggest these strikingly distinct fates be due to different permissiveness of the local CNS environment. Based on previously reported GPR17 activation by emergency signals (e.g., Stromal Derived Factor-1), we propose that a marked inflammatory milieu, such as that reproduced in EAE, induces GPR17 overactivation resulting in impaired downregulation, untimely and prolonged permanence in OPCs, leading, in turn, to differentiation blockade. Combined treatments with remyelinating agents and anti-inflammatory drugs may represent new potential adequate strategies to halt neurodegeneration and foster recovery. © 2018 The Authors GLIA Published by Wiley Periodicals, Inc.

  1. [The degree of chronic renal failure is associated with the rate of pro-inflammatory cytokines, hyperhomocysteinemia and with oxidative stress].

    Science.gov (United States)

    Tbahriti, H F; Messaoudi, A; Kaddous, A; Bouchenak, M; Mekki, K

    2014-06-01

    To evaluate pro-inflammatory cytokines, homocysteinemia and markers of oxidative status in the course of chronic renal failure. One hundred and two patients (male/female: 38/64; age: 45±07 years) with chronic renal failure were divided into 4 groups according to the National Kidney Foundation classification. They included 28 primary stage renal failure patients, 28 moderate stage renal failure, 28 severe stage renal failure and 18 end stage renal failure. The inflammatory status was evaluated by the determination of pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-1β, interleukin-6) and total homocysteine. Pro-oxidant status was assessed by assaying thiobarbituric acid reactive substances, hydroperoxides, and protein carbonyls. Antioxidant defence was performed by analysis of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase. Inflammatory markers were elevated in the end stage renal failure group compared to the other groups (Prenal failure group in comparison with the other groups (Prenal function is closely associated with the elevation of inflammatory markers leading to both increased markers of oxidative stress and decreased antioxidant defense. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  2. Involvement of chronic epipharyngitis in autoimmune (auto-inflammatory) syndrome induced by adjuvants (ASIA).

    Science.gov (United States)

    Hotta, Osamu; Tanaka, Ayaki; Torigoe, Akira; Imai, Kazuaki; Ieiri, Norio

    2017-02-01

    The epipharynx is an immunologically active site even under normal conditions, and enhanced immunologic activation is prone to occur in response to an upper respiratory infection, air pollution, and possibly to vaccine adjuvants. Due to the potential link between the central nervous system and immune function, a relationship between epipharyngitis and autonomic nervous disturbance as well as autoimmune disease has been suggested. Various functional somatic symptoms have been described after human papillomavirus (HPV) vaccination, although a causal relationship has not been established. We examined the epipharynx in young women showing functional somatic symptoms following HPV vaccination. Surprisingly, despite having minimal symptoms involving the pharynx, all patients were found to have severe epipharyngitis. In addition, significant improvement in symptoms was seen in most patients who underwent epipharyngeal treatment. Thus, we speculate that the chronic epipharyngitis potentially caused by the vaccine adjuvant may be involved in the pathogenesis of functional somatic syndrome (FSS) post-HPV vaccination. Further, we suggest that epipharyngeal treatment may be effective for various types of FSS regardless of the initial cause, as well as for some autoimmune diseases, and that this may be an important direction in future research.

  3. Modulation of the immune response by Fonsecaea pedrosoi morphotypes in the course of experimental chromoblastomycosis and their role on inflammatory response chronicity.

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    Isaque Medeiros Siqueira

    2017-03-01

    Full Text Available A common theme across multiple fungal pathogens is their ability to impair the establishment of a protective immune response. Although early inflammation is beneficial in containing the infection, an uncontrolled inflammatory response is detrimental and may eventually oppose disease eradication. Chromoblastomycosis (CBM, a cutaneous and subcutaneous mycosis, caused by dematiaceous fungi, is capable of inducing a chronic inflammatory response. Muriform cells, the parasitic form of Fonsecaea pedrosoi, are highly prevalent in infected tissues, especially in long-standing lesions. In this study we show that hyphae and muriform cells are able to establish a murine CBM with skin lesions and histopathological aspects similar to that found in humans, with muriform cells being the most persistent fungal form, whereas mice infected with conidia do not reach the chronic phase of the disease. Moreover, in injured tissue the presence of hyphae and especially muriform cells, but not conidia, is correlated with intense production of pro-inflammatory cytokines in vivo. High-throughput RNA sequencing analysis (RNA-Seq performed at early time points showed a strong up-regulation of genes related to fungal recognition, cell migration, inflammation, apoptosis and phagocytosis in macrophages exposed in vitro to muriform cells, but not conidia. We also demonstrate that only muriform cells required FcγR and Dectin-1 recognition to be internalized in vitro, and this is the main fungal form responsible for the intense inflammatory pattern observed in CBM, clarifying the chronic inflammatory reaction observed in most patients. Furthermore, our findings reveal two different fungal-host interaction strategies according to fungal morphotype, highlighting fungal dimorphism as an important key in understanding the bipolar nature of inflammatory response in fungal infections.

  4. Tryptophan Metabolism in Patients With Chronic Kidney Disease Secondary to Type 2 Diabetes: Relationship to Inflammatory Markers

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    Subrata Debnath

    2017-03-01

    Full Text Available Objective: Type 2 diabetes (T2D is the primary case of chronic kidney disease (CKD. Inflammation is associated with metabolic dysregulation in patients with T2D and CKD. Tryptophan (TRP metabolism may have relevance to the CKD outcomes and associated symptoms. We investigated the relationships of TRP metabolism with inflammatory markers in patients with T2D and CKD. Methods: Data were collected from a well-characterized cohort of type 2 diabetic individuals with all stages of CKD, including patients on hemodialysis. Key TRP metabolites (kynurenine [KYN], kynurenic acid [KYNA], and quinolinic acid [QA], proinflammatory cytokines (tumor necrosis factor-α [TNF-α] and interleukin-6 [IL-6], and C-reactive protein were measured in plasma. The KYN/TRP ratio was utilized as a surrogate marker for indoleamine 2,3-dioxygenase 1 (IDO1 enzyme activity. Results: There was a significant inverse association between circulating TRP level and stages of CKD ( P  < 0.0001. Downstream bioactive TRP metabolites KYN, KYNA, and QA were positively and robustly correlated with the severity of kidney disease ( P  < 0.0001. In multiple linear regression, neither TNF-α nor IL-6 was independently related to KYN/TRP ratio after adjusting for estimated glomerular filtration rate (eGFR. Only TNF-α was independently related to KYN after taking into account the effect of eGFR. Conclusions: Chronic kidney disease secondary to T2D may be associated with accumulation of toxic TRP metabolites due to both inflammation and impaired kidney function. Future longitudinal studies to determine whether the accumulation of KYN directly contributes to CKD progression and associated symptoms in patients with T2D are warranted.

  5. The potential anti-inflammatory effect of tetrahydrobiopterin administration in renal mass reduction-induced chronic renal failure in rats

    International Nuclear Information System (INIS)

    Korish, Aida A.; Arafah, Maha M.

    2007-01-01

    Objective was to investigate the impact of tetrahydrobiopterin (BH4) supplementation on the markers of inflammation and on the histological picture of the kidney in chronic renal failure C-reactive protein (CRF) induced in rats by subtotal nephrectomy (SNx). This study was performed at the Faculty of Medicine, King Saud University, Riyadh, Saudi Arabia during the period from December 2005 to January 2007. Chronic renal failure was induced by 5/6 SNx in 20 male Wister rats and another 10 rats were sham operated by flank incision and served as controls. Ten SNx rats received 10 mg/kg-1 BH4 intraperitoneally daily for 4 weeks. Plasma C-reactive protein (CRP), interlukin-6 (IL-6), malondialdehyde (MDA) and kidney functions were measured in all rats. Histopathological examination of kidney tissues was also performed. Untreated CRF rats showed significant elevation of plasma CRP, IL-6 and MDA levels and significant decrease in plasma albumin and total protein levels, tubuloglomerular fibrosis and interstitial tubular infiltration with inflammatory cells in comparison with the sham-operated rats. Tetrahydrobiopterin treatment decreased CRP, IL-6, MDA levels and decreased tubuloglomerular fibrosis and interstitial inflammation in treated CRF rats. Supplementation with exogenous BH4 decreased markers of inflammation and protected the kidney against post-renal mass reduction histological damage. Restoration of intracellular BH4 balance could normalize nitrous oxide production. Therefore, BH4 might be a promising strategy in attenuating inflammation in CRF. This may decrease endothelial dysfunction and limit the associated cardiovascular morbidity and mortality of this disease. (author)

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

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    Hulya Uzkeser

    2012-01-01

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

  7. The Effect of Electroacupuncture on PKMzeta in the ACC in Regulating Anxiety-Like Behaviors in Rats Experiencing Chronic Inflammatory Pain

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    Junying Du

    2017-01-01

    Full Text Available Chronic inflammatory pain can induce emotional diseases. Electroacupuncture (EA has effects on chronic pain and pain-related anxiety. Protein kinase Mzeta (PKMzeta has been proposed to be essential for the maintenance of pain and may interact with GluR1 to maintain CNS plasticity in the anterior cingulate cortex (ACC. We hypothesized that the PKMzeta-GluR1 pathway in the ACC may be involved in anxiety-like behaviors of chronic inflammatory pain and that the mechanism of EA regulation of pain emotion may involve the PKMzeta pathway in the ACC. Our results showed that chronic inflammatory pain model decreased the paw withdrawal threshold (PWT and increased anxiety-like behaviors. The protein expression of PKCzeta, p-PKCzeta (T560, PKMzeta, p-PKMzeta (T560, and GluR1 in the ACC of the model group were remarkably enhanced. EA increased PWT and alleviated anxiety-like behaviors. EA significantly inhibited the protein expression of p-PKMzeta (T560 in the ACC, and only a downward trend effect for other substances. Further, the microinjection of ZIP remarkably reversed PWT and anxiety-like behaviors. The present study provides direct evidence that the PKCzeta/PKMzeta-GluR1 pathway is related to pain and pain-induced anxiety-like behaviors. EA treatment both increases pain-related somatosensory behavior and decreases pain-induced anxiety-like behaviors by suppressing PKMzeta activity in the ACC.

  8. Associations between inflammatory cells infiltrating the ethmoid sinus mucosa, and nasal polyp size and grade of ethmoid sinus opacification on CT images in chronic sinusitis

    International Nuclear Information System (INIS)

    Imajima, Naotoshi; Watanabe, So; Furuta, Atsuko; Shimizu, Toshiyuki; Yamada, Naohiro; Mochizuki, Yuichiro; Suzaki, Harumi

    2009-01-01

    We investigated the types and numbers of inflammatory cells that infiltrated the ethmoid sinus mucosa in cases of chronic sinusitis in order to identify any associations with nasal polyp size and the grade of ethmoid sinus opacification on computer tomography images. The subjects were patients with chronic sinusitis who underwent endoscopic sinus surgery. Seventeen subjects also had bronchial asthma as a complication (six with aspirin-induced asthma, 11 with another form of asthma) and 24 did not have bronchial asthma as a complication (16 with allergic rhinitis, 8 with chronic sinusitis alone). The nasal polyps in the patients with bronchial asthma were significantly larger than those in the patients without bronchial asthma. Investigation of the numbers of infiltrating inflammatory cells according to polyp size revealed significantly more eosinophils as polyp size increased. In addition, infiltration of significantly more mast cells was observed when the polyps were large. Assessment of the grade of opacification of the ethmoid sinuses on computer tomography images showed a significantly higher grade of opacification in the patients with bronchial asthma than in the patients without bronchial asthma. Comparisons between the grade of opacification of the ethmoid sinuses and the number of infiltrating inflammatory cells revealed significantly more infiltrating eosinophils and mast cells in the patients with intense ethmoid sinus opacification. The above findings suggest that eosinophils and mast cells play a major role in forming the persistent inflammation of the sinus mucosa and nasal polyp tissue of patients with chronic sinusitis complicated by bronchial asthma. (author)

  9. Selective Vitamin D Receptor Activation as Anti-Inflammatory Target in Chronic Kidney Disease

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    J. Donate-Correa

    2014-01-01

    Full Text Available Paricalcitol, a selective vitamin D receptor (VDR activator used for treatment of secondary hyperparathyroidism in chronic kidney disease (CKD, has been associated with survival advantages, suggesting that this drug, beyond its ability to suppress parathyroid hormone, may have additional beneficial actions. In this prospective, nonrandomised, open-label, proof-of-concept study, we evaluated the hypothesis that selective vitamin D receptor activation with paricalcitol is an effective target to modulate inflammation in CKD patients. Eight patients with an estimated glomerular filtration rate between 15 and 44 mL/min/1.73 m2 and an intact parathyroid hormone (PTH level higher than 110 pg/mL received oral paricalcitol (1 μg/48 hours as therapy for secondary hyperparathyroidism. Nine patients matched by age, sex, and stage of CKD, but a PTH level <110 pg/mL, were enrolled as a control group. Our results show that five months of paricalcitol administration were associated with a reduction in serum concentrations of hs-CRP (13.9%, P<0.01, TNF-α (11.9%, P=0.01, and IL-6 (7%, P<0.05, with a nonsignificant increase of IL-10 by 16%. In addition, mRNA expression levels of the TNFα and IL-6 genes in peripheral blood mononuclear cells decreased significantly by 30.8% (P=0.01 and 35.4% (P=0.01, respectively. In conclusion, selective VDR activation is an effective target to modulate inflammation in CKD.

  10. CSF free light chain identification of demyelinating disease: comparison with oligoclonal banding and other CSF indexes.

    Science.gov (United States)

    Gurtner, Kari M; Shosha, Eslam; Bryant, Sandra C; Andreguetto, Bruna D; Murray, David L; Pittock, Sean J; Willrich, Maria Alice V

    2018-02-19

    Cerebrospinal fluid (CSF) used in immunoglobulin gamma (IgG) index testing and oligoclonal bands (OCBs) are common laboratory tests used in the diagnosis of multiple sclerosis. The measurement of CSF free light chains (FLC) could pose as an alternative to the labor-intensive isoelectric-focusing (IEF) gels used for OCBs. A total of 325 residual paired CSF and serum specimens were obtained after physician-ordered OCB IEF testing. CSF kappa (cKFLC) and lambda FLC (cLFLC), albumin and total IgG were measured. Calculations were performed based on combinations of analytes: CSF sum of kappa and lambda ([cKFLC+cLFLC]), kappa-index (K-index) ([cKFLC/sKFLC]/[CSF albumin/serum albumin]), kappa intrathecal fraction (KFLCIF) {([cKFLC/sKFLC]-[0.9358×CSF albumin/serum albumin]^[0.6687×sKFLC]/cKFLC)} and IgG-index ([CSF IgG/CSF albumin]/[serum IgG/serum albumin]). Patients were categorized as: demyelination (n=67), autoimmunity (n=53), non-inflammatory (n=50), inflammation (n=38), degeneration (n=28), peripheral neuropathy (n=24), infection (n=13), cancer (n=11), neuromyelitis optica (n=10) and others (n=31). cKFLC measurement used alone at a cutoff of 0.0611 mg/dL showed >90% agreement to OCBs, similar or better performance than all other calculations, reducing the number of analytes and variables. When cases of demyelinating disease were reviewed, cKFLC measurements showed 86% clinical sensitivity/77% specificity. cKFLC alone demonstrates comparable performance to OCBs along with increased sensitivity for demyelinating diseases. Replacing OCB with cKFLC would alleviate the need for serum and CSF IgG and albumin and calculated conversions. cKFLC can overcome challenges associated with performance, interpretation, and cost of traditional OCBs, reducing costs and maintaining sensitivity and specificity supporting MS diagnosis.

  11. Epstein-Barr virus viral load and serology in childhood non-Hodgkin's lymphoma and chronic inflammatory conditions in Uganda: implications for disease risk and characteristics.

    Science.gov (United States)

    Orem, Jackson; Sandin, Sven; Mbidde, Edward; Mangen, Fred Wabwire; Middeldorp, Jaap; Weiderpass, Elisabete

    2014-10-01

    Epstein-Barr virus (EBV) has been linked to malignancies and chronic inflammatory conditions. In this study, EBV detection was compared in children with non-Hodgkin's lymphoma and children with chronic inflammatory conditions, using samples and data from a case-control study carried out at the Mulago National Referral Hospital between 2004 and 2008. EBV viral load was measured in saliva, whole blood and white blood cells by real-time PCR. Serological values for IgG-VCA, EBNA1, and EAd-IgG were compared in non-Hodgkin's lymphoma and chronic inflammatory conditions; and in Burkitt's lymphoma and other subtypes of non-Hodgkin's lymphoma. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated. Of the 127 children included (87 males and 40 females; median age 7 years, range 2-17), 96 had non-Hodgkin's lymphoma (46 Burkitt's lymphoma and 50 other non-Hodgkin's lymphoma), 31 had chronic inflammatory conditions, and only 10% were HIV-positive. The most common clinical presentations for all disease categories considered were fever, night sweats, and weight loss. EBV viral load in whole blood was elevated in Burkitt's lymphoma compared to other non-Hodgkin's lymphoma (OR 6.67, 95% CI 1.32, 33.69; P-value = 0.04), but EBV viral loads in saliva and white blood cells were not different in any of the disease categories considered. A significant difference in EAd-IgG was observed when non-Hodgkin's lymphoma was compared with chronic inflammatory conditions (OR 0.19, 95% CI 0.07, 0.51; P-value = 0.001). When compared to chronic inflammatory conditions, EBV viral load was elevated in Burkitt's lymphoma, and EA IgG was higher in non-Hodgkin's lymphoma. This study supports an association between virological and serological markers of EBV and childhood non-Hodgkin's lymphoma, irrespective of subtype, in Uganda. © 2014 Wiley Periodicals, Inc.

  12. Curcumin-loaded nanoparticles ameliorate glial activation and improve myelin repair in lyolecithin-induced focal demyelination model of rat corpus callosum.

    Science.gov (United States)

    Naeimi, Reza; Safarpour, Fatemeh; Hashemian, Mona; Tashakorian, Hamed; Ahmadian, Seyed Raheleh; Ashrafpour, Manouchehr; Ghasemi-Kasman, Maryam

    2018-05-01

    Curcumin has been introduced as effective anti-inflammatory agent in treatment of several inflammatory disorders. Despite the wide range pharmacological activities, clinical application of curcumin is restricted mainly due to the low water solubility of this substance. More recently, we could remarkably improve the aqueous solubility of curcumin by its encapsulation in chitosan-alginate-sodium tripolyphosphate nanoparticles (CS-ALG-STPP NPs). In this study, the anti-inflammatory and myelin protective effects of curcumin-loaded NPs were evaluated in lysolecithin (LPC)-induced focal demyelination model. Pharmacokinetic of curcumin was assessed using high performance liquid chromatography (HPLC). Local demyelination was induced by injection of LPC into corpus callosum of rats. Animals were pre-treated with intraperitoneal (i.p.) injections of curcumin or curcumin-loaded NPs at dose of 12.5 mg/kg, 10 days prior to LPC injection and the injections were continued for 7 or 14 days post lesion. Hematoxylin and eosin (H&E) staining and immunostaining against activated glial cells including astrocytes and microglia were carried out for assessment of inflammation level in lesion site. Myelin specific staining was performed to evaluate the effect of curcumin-loaded NPs on myelination of LPC receiving animals. HPLC results showed the higher plasma concentration of curcumin after administration of NPs. Histological evaluation demonstrated that, the extent of demyelination areas was reduced in animals under treatment of curcumin-loaded NPs. Furthermore, treatment with curcumin-loaded NPs effectively attenuated glial activation and inflammation in LPC-induced demyelination model compared to curcumin receiving animals. Overall; these findings indicate that treatment with curcumin-loaded NPs preserve myelinated axons through amelioration of glial activation and inflammation in demyelination context. Copyright © 2018 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    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

  14. Inflammatory Biomarkers and Liver Histopathology in Non-Uremic and Uremic Chronic Hepatitis C Patients

    Directory of Open Access Journals (Sweden)

    Bengu Tatar

    2017-10-01

    Full Text Available Background: The aim of this study is to investigate the association between hepatic activity index (HAI and fibrosis score (FS with inflammation biomarkers in non-uremic and uremic hepatitis C positive patients. Methods: Fifty chronic hepatitis C (cHepC positive patients, having a liver biopsy were included in this study. Liver biopsies were scored according to modified ISHAC scoring system. 25 healthy controls of similar age and gender were also enrolled as control group. Serum YKL-40, neutrophil/lymphocyte ratio (NLR, thrombocyte/lymphocyte ratio (PLR, CRP and Immunoglobulin (IgG, A and M levels were used to determine inflammation. AST to Platelet Ratio Index (APRI score was also evaluated. According to biopsy findings patients were divided into 2 groups: low (0–2 and severe (3–6 FS. Results: Patients with cHepC had increased inflammation compared to the healthy controls. End-stage renal disease (ESRD patients had higher levels of inflammation markers (NLR, IgG, CRP and YKL-40 and lower HCV RNA levels, HAI and FS compared to non-uremic patients. When patients were grouped into 2 according to FS as mild and severe, IgG (p < 0.001, YKL-40 (p = 0.02 levels and APRI score (p = 0.002 were significantly higher compared to mild FS (p = 0.002. YKL-40 levels (t value: 3.48; p = 0.001 and APRI score (t value: 4.57, p < 0.001 were found as independent associated with FS in non-uremic patients. However, in adjusted models, only APRI score (t value: 3.98, p = 0.002 was an independent associated with FS in ESRD patients. Conclusion: In non-uremic cHepC patients, YKL-40 levels and APRI score may be valuable markers of FS. In ESRD patients, there is not sufficient data for prediction of HAI and FS. In these patients, APRI score may provide better information.

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

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    Miriam Maraslioglu

    2014-01-01

    Full Text Available 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.

  16. Chronic meningoencephalomyelitis with spastic spinal paralysis. Case report

    Energy Technology Data Exchange (ETDEWEB)

    Mitsuyama, Y; Thompson, L R; Yuki, I; Tanemori, H

    1973-01-01

    A case of chronic meningoencephalomyelitis in a 48-year-old housewife is presented. The onset was characterized by spastic paralysis of the lower extremities. The course was progressive with repeated remissions and exacerbations, and the patient died approximately 7 years after the onset of disease. Laboratory tests showed slightly increased cell count in the spinal fluid, accelerated sedimentation rate, positive CRP and RA, and increased ASLO and gamma globulin levels. Neuropathologic examination revealed such changes as perivascular cellular infiltration, glial nodules, poorly demarcated demyelination, and recent necrosis in the spinal cord and basal ganglia. Only mild inflammatory findings were noted in the telencephalon and brain stem. The clinicopathologic findings in this case supported a diagnosis of chronic meningoencepalomyelitis which could not be classified as any known type of encephalomyelitis. (auth)

  17. Research on Trypanosoma cruzi and Analysis of Inflammatory Infiltrate in Esophagus and Colon from Chronic Chagasic Patients with and without Mega

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    Eliângela de Castro Côbo

    2012-01-01

    Full Text Available To compare parasitism and inflammatory process in esophagus and colon from chronic chagasic patients, immunohistochemistry was carried out to research for T. cruzi and to evaluate the inflammatory infiltrate in the muscular and myenteric plexus in 39 esophagi (20 with and 19 without megaesophagus and 50 colons (25 with and 25 without megacolon. The frequency of T. cruzi in megaesophagus was 20%, and in megacolon it was 4%. No amastigotes were found in organs without mega; considering the total of esophagi (with and without mega, the frequency of T. cruzi would be 10% and 2% in the colon. Myositis and ganglionitis were more frequent and intense in organs with mega compared to those without mega, and in esophagus compared to colon. Qualitatively, inflammatory infiltration in esophagus and colon, with or without mega, was similar, consisting predominantly of T lymphocytes (CD3+, scarce macrophages (CD68+, and rare B lymphocytes (CD20+.

  18. Research on Trypanosoma cruzi and Analysis of Inflammatory Infiltrate in Esophagus and Colon from Chronic Chagasic Patients with and without Mega

    Science.gov (United States)

    Côbo, Eliângela de Castro; Silveira, Thales Parenti; Micheletti, Adilha Misson; Crema, Eduardo; Adad, Sheila Jorge

    2012-01-01

    To compare parasitism and inflammatory process in esophagus and colon from chronic chagasic patients, immunohistochemistry was carried out to research for T. cruzi and to evaluate the inflammatory infiltrate in the muscular and myenteric plexus in 39 esophagi (20 with and 19 without megaesophagus) and 50 colons (25 with and 25 without megacolon). The frequency of T. cruzi in megaesophagus was 20%, and in megacolon it was 4%. No amastigotes were found in organs without mega; considering the total of esophagi (with and without mega), the frequency of T. cruzi would be 10% and 2% in the colon. Myositis and ganglionitis were more frequent and intense in organs with mega compared to those without mega, and in esophagus compared to colon. Qualitatively, inflammatory infiltration in esophagus and colon, with or without mega, was similar, consisting predominantly of T lymphocytes (CD3+), scarce macrophages (CD68+), and rare B lymphocytes (CD20+). PMID:22131997

  19. Sensitization to epithelial antigens in chronic mucosal inflammatory disease. Characterization of human intestinal mucosa-derived mononuclear cells reactive with purified epithelial cell-associated components in vitro.

    OpenAIRE

    Roche, J K; Fiocchi, C; Youngman, K

    1985-01-01

    To explore the auto-reactive potential of cells infiltrating the gut mucosa in idiopathic chronic inflammatory bowel disease, intestinal lamina propria mononuclear cells (LPMC) were isolated, characterized morphologically and phenotypically, and evaluated for antigen-specific reactivity. The last was assessed by quantitating LPMC cytotoxic capabilities against purified, aqueous-soluble, organ-specific epithelial cell-associated components (ECAC) characterized previously. Enzyme-isolated infla...

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Richard F. Knoop

    2014-06-01

    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.

  2. The AMPK enzyme-complex: from the regulation of cellular energy homeostasis to a possible new molecular target in the management of chronic inflammatory disorders.

    Science.gov (United States)

    Antonioli, Luca; Colucci, Rocchina; Pellegrini, Carolina; Giustarini, Giulio; Sacco, Deborah; Tirotta, Erika; Caputi, Valentina; Marsilio, Ilaria; Giron, Maria Cecilia; Németh, Zoltán H; Blandizzi, Corrado; Fornai, Matteo

    2016-01-01

    Adenosine monophosphate-activated protein kinase (AMPK), known as an enzymatic complex that regulates the energetic metabolism, is emerging as a pivotal enzyme and enzymatic pathway involved in the regulation of immune homeostatic networks. It is also involved in the molecular mechanisms underlying the pathophysiology of chronic inflammatory diseases. AMPK is expressed in several immune cell types including macrophages, lymphocytes, neutrophils and dendritic cells, and governs a broad array of cell functions, which include cytokine production, chemotaxis, cytotoxicity, apoptosis and proliferation. Based on its wide variety of immunoregulatory actions, the AMPK system has been targeted to reveal its impact on the course of immune-related diseases, such as atherosclerosis, psoriasis, joint inflammation and inflammatory bowel diseases. The identification of AMPK subunits responsible for specific anti-inflammatory actions and the understanding of the underlying molecular mechanisms will promote the generation of novel AMPK activators, endowed with improved pharmacodynamic and pharmacokinetic profiles. These new tools will aid us to utilize AMPK pathway activation in the management of acute and chronic inflammatory diseases, while minimizing potential adverse reactions related to the effects of AMPK on metabolic energy.

  3. β2‑adrenergic receptor functionality and genotype in two different models of chronic inflammatory disease: Liver cirrhosis and osteoarthritis.

    Science.gov (United States)

    Roca, Reyes; Esteban, Pablo; Zapater, Pedro; Inda, María-Del-Mar; Conte, Anna Lucia; Gómez-Escolar, Laura; Martínez, Helena; Horga, José F; Palazon, José M; Peiró, Ana M

    2018-06-01

    The present study was designed to investigate the functional status of β2 adrenoceptors (β2AR) in two models of chronic inflammatory disease: liver cirrhosis (LC) and osteoarthritis (OA). The β2AR gene contains three single nucleotide polymorphisms at amino acid positions 16, 27 and 164. The aim of the present study was to investigate the potential influence of lymphocyte β2AR receptor functionality and genotype in LC and OA patients. Blood samples from cirrhotic patients (n=52, hepatic venous pressure gradient 13±4 mmHg, CHILD 7±2 and MELD 11±4 scores), OA patients (n=30, 84% Kellgren‑Lawrence severity 4 grade, 14% knee replacement joint) and healthy volunteers as control group (n=26) were analyzed. Peripheral blood mononuclear cells (PBMC) were isolated from whole blood and basal and isoproterenol induced adenylate cyclase activity (isoproterenol stimulus from 10‑9 to 10‑4 mM), and β2AR allelic variants (rs1042713, rs1042714, rs1800888) were determined. β2AR functionality was decreased in the two different models of chronic inflammatory disease studied, OA (50% vs. control) and LC (85% vs. control). In these patients, the strength of the β2AR response to adrenergic stimulation was very limited. Adrenergic modulation of PBMC function through the β2AR stimulus is decreased in chronic inflammatory processes including LC and OA, suggesting that the adrenergic system may be important in the development of these processes.

  4. History of chronic inflammatory disorders increases the risk of Merkel cell carcinoma, but does not correlate with Merkel cell polyomavirus infection.

    Science.gov (United States)

    Sahi, Helka; Sihto, Harri; Artama, Miia; Koljonen, Virve; Böhling, Tom; Pukkala, Eero

    2017-01-17

    We aimed to assess the connection between chronic inflammatory disorders (CIDs) and Merkel cell carcinoma (MCC). Merkel cell carcinoma cases diagnosed in 1978-2009 were extracted from the Finnish Cancer Registry and controls from the Population Registry. Information on reimbursed CIDs was linked to clinicopathological data including Merkel cell polyomavirus (MCV) status by qPCR and immunohistochemistry for the large T antigen of MCV (LTA), Ki-67 and tumour-infiltrating lymphocytes. Chronic inflammatory disorders increased the risk of MCC significantly (odds ratio (OR) 1.39, 95% confidence interval (CI) 1.03-1.88), specifically connective tissue/systemic diseases (OR 1.75, 95% CI 1.09-1.80) and diabetic conditions (OR 1.51, 95% CI 1.03-2.22). Chronic inflammatory disorders associated with larger tumour diameter (P=0.02) and higher Ki-67 expression (P=0.005). The expression of LTA was seen significantly more often in the absence of CIDs (P=0.05). Patients with CID are at significantly higher risk for aggressive MCC. Merkel cell polyomavirus positivity is more common in MCC patients unafflicted by CID.

  5. Alteration of synaptic connectivity of oligodendrocyte precursor cells following demyelination

    Science.gov (United States)

    Sahel, Aurélia; Ortiz, Fernando C.; Kerninon, Christophe; Maldonado, Paloma P.; Angulo, María Cecilia; Nait-Oumesmar, Brahim

    2015-01-01

    Oligodendrocyte precursor cells (OPCs) are a major source of remyelinating oligodendrocytes in demyelinating diseases such as Multiple Sclerosis (MS). While OPCs are innervated by unmyelinated axons in the normal brain, the fate of such synaptic contacts after demyelination is still unclear. By combining electrophysiology and immunostainings in different transgenic mice expressing fluorescent reporters, we studied the synaptic innervation of OPCs in the model of lysolecithin (LPC)-induced demyelination of corpus callosum. Synaptic innervation of reactivated OPCs in the lesion was revealed by the presence of AMPA receptor-mediated synaptic currents, VGluT1+ axon-OPC contacts in 3D confocal reconstructions and synaptic junctions observed by electron microscopy. Moreover, 3D confocal reconstructions of VGluT1 and NG2 immunolabeling showed the existence of glutamatergic axon-OPC contacts in post-mortem MS lesions. Interestingly, patch-clamp recordings in LPC-induced lesions demonstrated a drastic decrease in spontaneous synaptic activity of OPCs early after demyelination that was not caused by an impaired conduction of compound action potentials. A reduction in synaptic connectivity was confirmed by the lack of VGluT1+ axon-OPC contacts in virtually all rapidly proliferating OPCs stained with EdU (50-ethynyl-20-deoxyuridine). At the end of the massive proliferation phase in lesions, the proportion of innervated OPCs rapidly recovers, although the frequency of spontaneous synaptic currents did not reach control levels. In conclusion, our results demonstrate that newly-generated OPCs do not receive synaptic inputs during their active proliferation after demyelination, but gain synapses during the remyelination process. Hence, glutamatergic synaptic inputs may contribute to inhibit OPC proliferation and might have a physiopathological relevance in demyelinating disorders. PMID:25852473

  6. Hypothalamic GPR40 signaling activated by free long chain fatty acids suppresses CFA-induced inflammatory chronic pain.

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    Kazuo Nakamoto

    Full Text Available GPR40 has been reported to be activated by long-chain fatty acids, such as docosahexaenoic acid (DHA. However, reports studying functional role of GPR40 in the brain are lacking. The present study focused on the relationship between pain regulation and GPR40, investigating the functional roles of hypothalamic GPR40 during chronic pain caused using a complete Freund's adjuvant (CFA-induced inflammatory chronic pain mouse model. GPR40 protein expression in the hypothalamus was transiently increased at day 7, but not at days 1, 3 and 14, after CFA injection. GPR40 was co-localized with NeuN, a neuron marker, but not with glial fibrillary acidic protein (GFAP, an astrocyte marker. At day 1 after CFA injection, GFAP protein expression was markedly increased in the hypothalamus. These increases were significantly inhibited by the intracerebroventricular injection of flavopiridol (15 nmol, a cyclin-dependent kinase inhibitor, depending on the decreases in both the increment of GPR40 protein expression and the induction of mechanical allodynia and thermal hyperalgesia at day 7 after CFA injection. Furthermore, the level of DHA in the hypothalamus tissue was significantly increased in a flavopiridol reversible manner at day 1, but not at day 7, after CFA injection. The intracerebroventricular injection of DHA (50 µg and GW9508 (1.0 µg, a GPR40-selective agonist, significantly reduced mechanical allodynia and thermal hyperalgesia at day 7, but not at day 1, after CFA injection. These effects were inhibited by intracerebroventricular pretreatment with GW1100 (10 µg, a GPR40 antagonist. The protein expression of GPR40 was colocalized with that of β-endorphin and proopiomelanocortin, and a single intracerebroventricular injection of GW9508 (1.0 µg significantly increased the number of neurons double-stained for c-Fos and proopiomelanocortin in the arcuate nucleus of the hypothalamus. Our findings suggest that hypothalamic GPR40 activated by free long

  7. Hypothalamic GPR40 signaling activated by free long chain fatty acids suppresses CFA-induced inflammatory chronic pain.

    Science.gov (United States)

    Nakamoto, Kazuo; Nishinaka, Takashi; Sato, Naoya; Mankura, Mitsumasa; Koyama, Yutaka; Kasuya, Fumiyo; Tokuyama, Shogo

    2013-01-01

    GPR40 has been reported to be activated by long-chain fatty acids, such as docosahexaenoic acid (DHA). However, reports studying functional role of GPR40 in the brain are lacking. The present study focused on the relationship between pain regulation and GPR40, investigating the functional roles of hypothalamic GPR40 during chronic pain caused using a complete Freund's adjuvant (CFA)-induced inflammatory chronic pain mouse model. GPR40 protein expression in the hypothalamus was transiently increased at day 7, but not at days 1, 3 and 14, after CFA injection. GPR40 was co-localized with NeuN, a neuron marker, but not with glial fibrillary acidic protein (GFAP), an astrocyte marker. At day 1 after CFA injection, GFAP protein expression was markedly increased in the hypothalamus. These increases were significantly inhibited by the intracerebroventricular injection of flavopiridol (15 nmol), a cyclin-dependent kinase inhibitor, depending on the decreases in both the increment of GPR40 protein expression and the induction of mechanical allodynia and thermal hyperalgesia at day 7 after CFA injection. Furthermore, the level of DHA in the hypothalamus tissue was significantly increased in a flavopiridol reversible manner at day 1, but not at day 7, after CFA injection. The intracerebroventricular injection of DHA (50 µg) and GW9508 (1.0 µg), a GPR40-selective agonist, significantly reduced mechanical allodynia and thermal hyperalgesia at day 7, but not at day 1, after CFA injection. These effects were inhibited by intracerebroventricular pretreatment with GW1100 (10 µg), a GPR40 antagonist. The protein expression of GPR40 was colocalized with that of β-endorphin and proopiomelanocortin, and a single intracerebroventricular injection of GW9508 (1.0 µg) significantly increased the number of neurons double-stained for c-Fos and proopiomelanocortin in the arcuate nucleus of the hypothalamus. Our findings suggest that hypothalamic GPR40 activated by free long chain fatty

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

    Directory of Open Access Journals (Sweden)

    Bin Su

    Full Text Available 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.

  9. Research Article. Comparative Analysis of Hepcidin-25 and Inflammatory Markers in Patients with Chronic Kidney Disease with and without Anemia

    Directory of Open Access Journals (Sweden)

    Căldăraru Carmen Denise

    2017-03-01

    Full Text Available Introduction: Hepcidin is a regulatory protein in iron metabolism; we do not know the role in chronic kidney disease anemia. Methods: 22 patients with CKD anemia and 15 patients with CKD without anemia were investigated. CKD anemia-inclusion criteria: over 18 years, hemoglobin ≤12 g/dl for women and ≤13 g/dl for men, no treatment for anemia 6 months before enrollment, glomerular filtration rate (eGFR <60 ml/min/1.73m2 and stable creatinine three months before enrollment. Exclusion criteria: infection, bleeding, malignancy, systemic or liver disease, immunosuppression, renal replacement therapy. CKD without anemia-inclusion criteria: over 18 years, no anemia or treatment for anemia, CKD with stable creatinine values three months before enrollment. Exclusion criteria: medical conditions known to have a role in the development of polycythemia. Hepcidin-25 and ferritin were measured by ELISA method. Erythropoietin (EPO, tumor necrosis factor (TNF-α, interleukin (IL-6 were evaluated using chemiluminescent enzyme immunometric assays. Unpaired T test, Pearson correlation and multiple regression were used for statistical analysis. Results: Hemoglobin values were significantly lower in anemia group. There were no differences in terms of eGFR, age, body mass index, serum hepcidin, erythropoietin, fibrinogen, IL-6, and TNF-α between CKD patients with and without anemia. Serum hepcidin correlated positively with ferritin (r=0.45 p<0.05, TNF-α (r=0.54, p<0.05 and negatively with erythropoietin (r=-0.51, p<0.05. Multiple linear regression analysis demonstrated that TNF-α is an independent predictor of serum hepcidin in our patients (p=0.003, R=0.71. Conclusion: We found no differences in serum hepcidin, erythropoietin and inflammatory markers in non-dialysis CKD patients with and without anemia.

  10. Erhuang Formula ameliorates renal damage in adenine-induced chronic renal failure rats via inhibiting inflammatory and fibrotic responses.

    Science.gov (United States)

    Zhang, Chun-Yan; Zhu, Jian-Yong; Ye, Ying; Zhang, Miao; Zhang, Li-Jun; Wang, Su-Juan; Song, Ya-Nan; Zhang, Hong

    2017-11-01

    The present study aimed to evaluate the protective effects of Erhuang Formula (EHF) and explore its pharmacological mechanisms on adenine-induced chronic renal failure (CRF). The compounds in EHF were analyzed by HPLC/MS. Adenine-induced CRF rats were administrated by EHF. The effects were evaluated by renal function examination and histology staining. Immunostaining of some proteins related cell adhesion was performedin renal tissues, including E-cadherin, β-catenin, fibronectin and laminin. The qRT-PCR was carried out determination of gene expression related inflammation and fibrosis including NF-κB, TNF-α, TGF-β1, α-SMA and osteopontin (OPN). Ten compounds in EHF were identified including liquiritigenin, farnesene, vaccarin, pachymic acid, cycloastragenol, astilbin, 3,5,6,7,8,3',4'-heptemthoxyflavone, physcion, emodin and curzerene. Abnormal renal function and histology had significant improvements by EHF treatment. The protein expression of β-catenin, fibronectin and laminin were significantly increased and the protein expression of E-cadherin significantly decreased in CRF groups. However, these protein expressions were restored to normal levels in EHF group. Furthermore, low expression of PPARγ and high expression of NF-κB, TNF-α, TGF-β1, α-SMA and OPN were substantially restored by EHF treatment in a dose-dependent manner. EHF ameliorated renal damage in adenine-induced CRF rats, and the mechanisms might involve in the inhibition of inflammatory and fibrotic responses and the regulation of PPARγ, NF-κB and TGF-β signaling pathways. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  11. [Effects of chronic intermittent hypoxia on oxidative stress and inflammatory response and the interventional roles of adiponectin].

    Science.gov (United States)

    Pan, Guoyu; Su, Mei; Ding, Wenxiao; Ding, Ning; Huang, Hanpeng; Zhang, Xilong

    2015-04-28

    To explore the effects of chronic intermittent hypoxia (CIH) on oxidative stress and inflammatory response and the interventional roles of adiponectin (Ad). A total of 45 male Wistar rats were randomly divided into three groups of control group, CIH and CIH+Ad (n = 15 each). The control group breathed room air while the CIH and CIH+Ad groups received CIH 8 h/d for 5 successive weeks. The CIH+Ad group Ad had an injection of 10 µg once a week through tail vein. At the end of experiment (Day 35), comparison was performed among three groups about Ad, tumor necrosis factor α (TNF-α), C-reactive protein (CRP) and interleukin (IL) 6 from serum as well as malondialdehyde, superoxide dismutase (SOD), myeloperoxidase (MPO), reactive oxygen spieces (ROS) and nuclear factor (NF) κB from genioglossus. Serum Ad level in CIH group was lower than those in control and CIH+Ad groups ((4 208 ± 2 239) vs (7 051 ± 2 432) and (6 405 ± 2 384) ng/ml, all P statistic difference between control and CIH+Ad groups. Both serum levels of TNF-α and CRP were higher in CIH group than those in control and CIH+Ad groups ((70.87 ± 35.16) vs (26.54 ± 20.32) and (29.50 ± 22.54) pg/ml, as well as (31.84 ± 11.48) vs (22.68 ± 9.63), (25.32 ± 8.34) mg/L, all P statistical difference with CIH+Ad group (1.04 ± 0.27). CIH may induce oxidative stress and inflammation possibly through NF κB pathway while a supplement of Ad attenuates the above CIH-induced responses.

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

    International Nuclear Information System (INIS)

    Okunieff, Paul; Xu Jianhua; Hu Dongping; Liu Weimin; Zhang Lurong; Morrow, Gary; Pentland, Alice; Ryan, Julie L.; Ding, Ivan M.D.

    2006-01-01

    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]-α, and lymphotoxin-β) or fibrogenic cytokines (transforming growth factor [TGF]-β) 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-α, and lymphotoxin-β) and the fibrogenic cytokine, TGF-β, 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

  13. Increased demyelination and axonal damage in metallothionein I+II-deficient mice during experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Penkowa, M; Espejo, C; Martínez-Cáceres, E M

    2003-01-01

    Metallothioneins I+II (MT-I+II) are antioxidant, neuroprotective factors. We previously showed that MT-I+II deficiency during experimental autoimmune encephalomyelitis (EAE) leads to increased disease incidence and clinical symptoms. Moreover, the inflammatory response of macrophages and T cells......, oxidative stress, and apoptotic cell death during EAE were increased by MT-I+II deficiency. We now show for the first time that demyelination and axonal damage are significantly increased in MT-I+II deficient mice during EAE. Furthermore, oligodendroglial regeneration, growth cone formation, and tissue...... repair including expression of trophic factors were significantly reduced in MT-I+II-deficient mice during EAE. Accordingly, MT-I+II have protective and regenerative roles in the brain....

  14. Postchikungunya Chronic Inflammatory Rheumatism

    Directory of Open Access Journals (Sweden)

    Keith A. Sacco

    2016-01-01

    Full Text Available A 65-year-old male resident of Guatemala presented with a 5-month history of distal symmetric arthritis and generalized fatigue. This was associated with night sweats, chills, and weight loss. Symptoms were refractory to oral prednisone and hydroxychloroquine.

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

    Science.gov (United States)

    Straub, Rainer H

    2014-09-01

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

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

    Directory of Open Access Journals (Sweden)

    Mathieu Darsigny

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

  17. A pilot evaluation of Arthritis Self-Management Program by lay leaders in patients with chronic inflammatory arthritis in Hong Kong.

    Science.gov (United States)

    Leung, Ying-Ying; Kwan, Jackie; Chan, Patsy; Poon, Peter K K; Leung, Christine; Tam, Lai-Shan; Li, Edmund K; Kwok, Anna

    2016-04-01

    The objectives of this paper are to evaluate the efficacy of a community-based lay-led Arthritis Self-Management Program (ASMP) among patients with chronic inflammatory arthritis and evaluate the effectiveness of "shared care collaboration" between hospital and community. We trained 17 lay leaders and recruited patients with chronic inflammatory arthritis via a new shared-care model between hospital rheumatology centers and community organizations. Participants were allocated to interventional group or a wait list control group. Evaluations were completed before, after (6 weeks), and 3 months after ASMP. We performed analysis of covariance with adjustment with age, sex, marital status, education, employment, duration of illness, and disability at baseline. A total of 65 participants and 32 controls completed the study. The mean (SD) age and duration of illness were 52.0 (11.4) and 5.6 (7.3) years, 90.7 % were female, 80.4 % had rheumatoid arthritis; 25.8, 53.6, and 12.4 % referrals were from hospitals, community organizations, and patient self-help groups, respectively. The interventional group had significantly less pain (p = 0.049 at 6 weeks), used more cognitive coping methods (p = 0.008 at 6 weeks, p = 0.041 at 3 months) and practiced more aerobic exercise (p = 0.049 at 6 weeks, p = 0.008 at 3 months) after adjustment of covariance. The interventional group had a trend of improvement in self-efficacy, fatigue, self-rated health, and health distress. A community-based lay-led ASMP showed positive beneficial effects on participants with chronic inflammatory arthritis. Shared-care collaboration between hospitals, community organizations, and patient self-help groups was demonstrated.

  18. Chronic aspiration of gastric and duodenal contents and their effects on inflammatory cytokine production in respiratory system of rats.

    OpenAIRE

    Mitra Samareh Fekri; Hamid Reza Poursalehi; Hamid Najafipour; Beydolah Shahouzahi; Nasrin Bazargan Harandi

    2014-01-01

    Gastroesophageal reflux disease (GERD) is defined with clinical symptoms of heart burning and regurgitation. It may be associated with external esophageal symptoms such as chronic cough, asthma, laryngitis, chronic lung disease, sinusitis and pulmonary fibrosis. In the present study, rats with chronic aspiration of gastroduodenal contents were studied for cellular phenotypes and cytokine concentrations in bronchoalveolar lavage and lung tissue. Thirty-six male Albino N-MRI rats were randomly ...

  19. Procyanidin B2 ameliorates carrageenan-induced chronic nonbacterial prostatitis in rats via anti-inflammatory and activation of the Nrf2 pathway.

    Science.gov (United States)

    Wang, Wei; Chen, Renzong; Wang, Jiye

    2017-11-04

    Prostatitis is one of the most prevalent problems in andriatry and urinary surgery. In the present study, we evaluated the effect of procyanidin B2 (PB) on carrageenan-induced chronic nonbacterial prostatitis in rats. Results showed that PB significantly decreased the prostatic index and enhanced the body weight inhibited by carrageenan. Biochemical results revealed that PB significantly lowered the prostatic specific antigen (PSA) and alleviated oxidative stress in serum. The levels of TNF-α, IL-6, and IL-10 in prostatic homogenate were also significantly decreased after PB treatment. We also found evidence that PB treatment reversed the suppression of Nrf2 nuclear translocation, and increased the expressions of NQO1 and HO-1 in the prostate glands. In conclusion, treatment with PB attenuates carrageenan-induced chronic nonbacterial prostatitis via anti-inflammatory and activation of the Nrf2 pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Demyelinating Disease following Anti-TNFa Treatment: A Causal or Coincidental Association? Report of Four Cases and Review of the Literature

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    E. Andreadou

    2013-01-01

    Full Text Available Tumor necrosis factor antagonists (anti-TNFa are an established therapeutic option for several autoimmune and inflammatory bowel diseases. Despite their clinical effectiveness, neurological adverse events have been reported and literature data suggest a potential role of anti-TNFa in the induction of demyelination of the CNS. We present four patients treated with anti-TNFa who developed symptoms suggestive of CNS demyelination. The first patient, a 17-year-old male who received etanercept for psoriatic arthritis for eight months, presented with dysesthesias up to T4 level. The second patient, a 30-year-old male treated with adalimumab for three years due to ankylosing spondylitis, presented with right unilateral tinnitus. The third case, a 47-year-old female, received etanercept for four years because of psoriatic arthritis and developed persistent headache and left-sided face and head numbness. Finally, the fourth patient, a 57-years-old female treated with etanercept for six years due to ankylosing spondylitis, presented with difficulty in speech, swallowing, and ptosis of the right corner of the mouth. In all cases, brain MRI showed lesions suggestive of demyelination, while positive oligoclonal bands were detected in the CSF. Anti-TNFa treatments were discontinued and patients showed clinical improvement with pulsed intravenous corticosteroid therapy. CNS demyelination following anti-TNFa treatment represents a relatively rare but potential serious complication. Close follow-up and MRI monitoring of these patients is mandatory to elucidate whether the clinical manifestations represent adverse events occurring during anti-TNFa therapy or a first demyelinating episode.

  1. Anti-inflammatory activity of Albizia lebbeck Benth., an ethnomedicinal plant, in acute and chronic animal models of inflammation.

    Science.gov (United States)

    Babu, N Prakash; Pandikumar, P; Ignacimuthu, S

    2009-09-07

    Albizia lebbeck Benth. is used both in Indian traditional system and folk medicine to treat several inflammatory pathologies such as asthma, arthritis and burns. The aim of the present study was to evaluate the scientific basis of anti-inflammatory activity of different organic solvent extracts of Albizia lebbeck. The anti-inflammatory activity of Albizia lebbeck was studied using the carrageenan, dextran, cotton pellet and Freund's complete adjuvant induced rat models. The extracts obtained using petroleum ether, chloroform and ethanol were administered at the concentrations of 100, 200 and 400mg/kg body weight. The petroleum ether and ethanol extracts at 400mg/kg, showed maximum inhibition of inflammation induced by carrageenan (petroleum ether-48.6%; ethanol-59.57%), dextran (petroleum ether-45.99%; ethanol-52.93%), cotton pellet (petroleum ether-34.46%; ethanol-53.57%) and Freund's adjuvant (petroleum ether-64.97%; ethanol-68.57%). The marked inhibitory effect on paw edema shows that Albizia lebbeck possesses remarkable anti-inflammatory activity, supporting the folkloric usage of the plant to treat various inflammatory diseases.

  2. Comparison of Specialty Medication Use for Common Chronic Inflammatory Diseases Among Health Exchange and Other Commercially Insured Members.

    Science.gov (United States)

    Chen, Xiaoxue; Gautam, Santosh; Ruggieri, Alexander; Richards, Thomas; Devries, Andrea; Sylwestrzak, Gosia

    2018-01-01

    The Affordable Care Act of 2010 allows the purchase of health insurance through special marketplaces called "health exchanges." The majority of individuals enrolling in the exchanges were previously uninsured, older, and sicker than other commercially insured members. Early evidence also suggests that exchange plan members use more costly specialty drugs compared with other commercially insured members. To (a) examine patient characteristics and specialty drug use for common chronic inflammatory diseases (CIDs) among exchange plan members compared with other commercially insured members and (b) explore variations in specialty drug use within exchange plans by metal tiers (bronze, silver, gold, and platinum), as well as across local markets. This analysis included adults aged ≥ 18 years who were enrolled in exchange plans (exchange population) and other commercial health plans (nonexchange population). The primary outcome was the likelihood of using specialty drugs prescribed to treat common CIDs, such as rheumatoid arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, psoriatic arthritis, and psoriasis. The adjusted likelihood of using CID specialty drugs was calculated from logistic regression controlling for prevalence of CIDs and other health risk factors. A total of 931,384 exchange plan members and 2,682,855 nonexchange plan members were included in the analysis. Compared with the nonexchange population, the exchange population was older, more likely to be female, had more comorbid conditions, but filled fewer prescriptions. The 2 groups were similar in terms of CID prevalence. The observed likelihood of CID specialty drug use was 20.0% lower in the exchange versus the nonexchange populations (341 users per 100,000 exchange members vs. 427 users per 100,000 nonexchange members; P exchange population, the observed likelihood of CID specialty drug use was 132 per 100,000 bronze plan members (69.1% lower than nonexchange); 326 per 100

  3. Spinal cord demyelination combined with hyperhomocysteinemia: a case report

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    Hao MM

    2014-11-01

    Full Text Available Meimei Hao, Yan Zhang, Shuangxing Hou, Yanling Chen, Ming Shi, Gang Zhao, Yanchun Deng Department of Neurology, Xijing Hospital, Fourth Military Medical University, Xi’an, People’s Republic of China Abstract: Hyperhomocysteinemia (HHcy has been recognized as an independent risk factor for atherosclerotic vascular disease. Here we report a patient who suffered from spinal cord demyelination combined with HHcy. The patient was admitted to our hospital with a diagnosis of acute myelitis. However, hormone therapy was ineffective. Further investigations revealed that he had HHcy and a homozygous mutation of the gene encoding methylenetetrahydrofolate reductase (MTHFR c.677C>T, which is a key enzyme involved in homocysteine metabolism. In view of these findings, we treated the patient with B vitamins and his symptoms gradually improved. Spinal magnetic resonance imaging performed 3 months after onset showed near recovery of the lesion. To our knowledge, similar reports are rare. Keywords: demyelination, hyperhomocysteinemia, homocysteine, methylenetetrahydrofolate reductase, methylation

  4. Targeted nanoparticles that mimic immune cells in pain control inducing analgesic and anti-inflammatory actions: a potential novel treatment of acute and chronic pain condition.

    Science.gov (United States)

    Hua, Susan; Cabot, Peter J

    2013-01-01

    injection using liquid scintillation counting (LSC). Administration of liposomes loaded with loperamide HCl, and conjugated with antibody to intercellular adhesion molecule-1 (anti-ICAM-1), exerted analgesic and anti-inflammatory effects exclusively in peripheral painful inflamed tissue. These targeted nanoparticles produced highly significant analgesic and anti-inflammatory effects over the 48 hour time course studied following intravenous administration in rats with Complete Freund's Adjuvant-induced inflammation of the paw. All control groups showed no significant antinociceptive or anti-inflammatory effects. Our biodistribution study demonstrated specific localization of the targeted nanoparticles to peripheral inflammatory tissue and no significant uptake into the brain. In vivo studies were performed in the well-established rodent model of acute inflammatory pain. We are currently studying this approach in chronic pain models known to have clinical activation of the peripheral immune-derived opioid response. The study presents a novel approach of opioid delivery specifically to injured tissues for pain control. The study also highlights a novel anti-inflammatory role for peripheral opioid targeting, which is of clinical relevance. The potential also exists for the modification of these targeted nanoparticles with other therapeutic compounds for use in other painful conditions.

  5. Comparison of electrophysiological findings in axonal and demyelinating Guillain-Barre syndrome

    Science.gov (United States)

    Yadegari, Samira; Nafissi, Shahriar; Kazemi, Neda

    2014-01-01

    Background: Incidence and predominant subtype of Guillain-Barre syndrome (GBS) differs geographically. Electrophysiology has an important role in early diagnosis and prediction of prognosis. This study is conducted to determine the frequent subtype of GBS in a large group of patients in Iran and compare nerve conduction studies in axonal and demyelinating forms of GBS. Methods: We retrospectively evaluated the medical records and electrodiagnostic study (EDS) of 121 GBS patients who were managed in our hospital during 11 years. After regarding the exclusion criteria, patients classified as three groups: acute inflammatory demyelinating polyneuropathy (AIDP), acute motor axonal neuropathy (AMAN), and acute motor sensory axonal neuropathy (AMSAN). The most frequent subtype and then electrophysiological characteristic based on the time of EDS and their cerebrospinal fluid (CSF) profile were assessed. Results: Among 70 patients finally included in the study, 67% were men. About 63%, 23%, and 14% had AIDP, AMAN, and AMSAN, respectively. AIDP patients represented a wider range of ages compared with other groups. Higher levels of CSF protein, abnormal late responses and sural sparing were more frequent in AIDP subtype. Five AMSAN patients also revealed sural sparing. Conduction block (CB) was observed in one AMAN patient. Prolonged F-wave latency was observed only in AIDP cases. CB and inexcitable sensory nerves were more frequent after 2 weeks, but reduced F-wave persistency was more prominent in the early phase. Conclusion: AIDP was the most frequent subtype. Although the electrophysiology and CSF are important diagnostic tools, classification should not be made based on a distinct finding. PMID:25422732

  6. Chronic intermittent hypoxia exerts CNS region-specific effects on rat microglial inflammatory and TLR4 gene expression.

    Directory of Open Access Journals (Sweden)

    Stephanie M C Smith

    Full Text Available Intermittent hypoxia (IH during sleep is a hallmark of sleep apnea, causing significant neuronal apoptosis, and cognitive and behavioral deficits in CNS regions underlying memory processing and executive functions. IH-induced neuroinflammation is thought to contribute to cognitive deficits after IH. In the present studies, we tested the hypothesis that IH would differentially induce inflammatory factor gene expression in microglia in a CNS region-dependent manner, and that the effects of IH would differ temporally. To test this hypothesis, adult rats were exposed to intermittent hypoxia (2 min intervals of 10.5% O2 for 8 hours/day during their respective sleep cycles for 1, 3 or 14 days. Cortex, medulla and spinal cord tissues were dissected, microglia were immunomagnetically isolated and mRNA levels of the inflammatory genes iNOS, COX-2, TNFα, IL-1β and IL-6 and the innate immune receptor TLR4 were compared to levels in normoxia. Inflammatory gene expression was also assessed in tissue homogenates (containing all CNS cells. We found that microglia from different CNS regions responded to IH differently. Cortical microglia had longer lasting inflammatory gene expression whereas spinal microglial gene expression was rapid and transient. We also observed that inflammatory gene expression in microglia frequently differed from that in tissue homogenates from the same region, indicating that cells other than microglia also contribute to IH-induced neuroinflammation. Lastly, microglial TLR4 mRNA levels were strongly upregulated by IH in a region- and time-dependent manner, and the increase in TLR4 expression appeared to coincide with timing of peak inflammatory gene expression, suggesting that TLR4 may play a role in IH-induced neuroinflammation. Together, these data indicate that microglial-specific neuroinflammation may play distinct roles in the effects of intermittent hypoxia in different CNS regions.

  7. Expression of annexin-A1 and galectin-1 anti-inflammatory proteins and mRNA in chronic gastritis and gastric cancer.

    Science.gov (United States)

    Jorge, Yvana Cristina; Mataruco, Mayra Mioto; Araújo, Leandro Pires; Rossi, Ana Flávia Teixeira; de Oliveira, Juliana Garcia; Valsechi, Marina Curado; Caetano, Alaor; Miyazaki, Kenji; Fazzio, Célia Sebastiana de Jesus; Thomé, Jorge Alberto; Rahal, Paula; Oliani, Sonia Maria; Silva, Ana Elizabete

    2013-01-01

    The anti-inflammatory proteins annexin-A1 and galectin-1 have been associated with tumor progression. This scenario prompted us to investigate the relationship between the gene and protein expression of annexin-A1 (ANXA1/AnxA1) and galectin-1 (LGALS1/Gal-1) in an inflammatory gastric lesion as chronic gastritis (CG) and gastric adenocarcinoma (GA) and its association with H. pylori infection. We analyzed 40 samples of CG, 20 of GA, and 10 of normal mucosa (C) by the quantitative real-time PCR (qPCR) technique and the immunohistochemistry assay. High ANXA1 mRNA expression levels were observed in 90% (36/40) of CG cases (mean relative quantification RQ = 4.26  ±  2.03) and in 80% (16/20) of GA cases (mean RQ = 4.38  ±  4.77). However, LGALS1 mRNA levels were high (mean RQ = 2.44  ±  3.26) in 60% (12/20) of the GA cases, while low expression was found in CG (mean RQ = 0.43 ± 3.13; P gastritis and gastric cancer, suggesting a strong association of these proteins with chronic gastric inflammation and carcinogenesis.

  8. Myeloperoxidase-Related Chlorination Activity Is Positively Associated with Circulating Ceruloplasmin in Chronic Heart Failure Patients: Relationship with Neurohormonal, Inflammatory, and Nutritional Parameters

    Directory of Open Access Journals (Sweden)

    Aderville Cabassi

    2015-01-01

    Full Text Available Rationale. Heart failure (HF is accompanied by the development of an imbalance between oxygen- and nitric oxide-derived free radical production leading to protein nitration. Both chlorinating and peroxidase cycle of Myeloperoxidase (MPO contribute to oxidative and nitrosative stress and are involved in tyrosine nitration of protein. Ceruloplasmin (Cp has antioxidant function through its ferroxidase I (FeOxI activity and has recently been proposed as a physiological defense mechanism against MPO inappropriate actions. Objective. We investigated the relationship between plasma MPO-related chlorinating activity, Cp and FeOxI, and nitrosative stress, inflammatory, neurohormonal, and nutritional biomarkers in HF patients. Methods and Results. In chronic HF patients (n=81, 76 ± 9 years, NYHA Class II (26; Class III (29; Class IV (26 and age-matched controls (n=17, 75 ± 11 years, CTR, plasma MPO chlorinating activity, Cp, FeOxI, nitrated protein, free Malondialdehyde, BNP, norepinephrine, hsCRP, albumin, and prealbumin were measured. Plasma MPO chlorinating activity, Cp, BNP, norepinephrine, and hsCRP were increased in HF versus CTR. FeOxI, albumin, and prealbumin were decreased in HF. MPO-related chlorinating activity was positively related to Cp (r= 0.363, P<0.001, nitrated protein, hsCRP, and BNP and inversely to albumin. Conclusions. Plasma MPO chlorinated activity is increased in elderly chronic HF patients and positively associated with Cp, inflammatory, neurohormonal, and nitrosative parameters suggesting a role in HF progression.

  9. A Proposal for a Study on Treatment Selection and Lifestyle Recommendations in Chronic Inflammatory Diseases: A Danish Multidisciplinary Collaboration on Prognostic Factors and Personalised Medicine

    Directory of Open Access Journals (Sweden)

    Vibeke Andersen

    2017-05-01

    Full Text Available Chronic inflammatory diseases (CIDs, including Crohn’s disease and ulcerative colitis (inflammatory bowel diseases, IBD, rheumatoid arthritis, psoriasis, psoriatic arthritis, spondyloarthritides, hidradenitis suppurativa, and immune-mediated uveitis, are treated with biologics targeting the pro-inflammatory molecule tumour necrosis factor-α (TNF (i.e., TNF inhibitors. Approximately one-third of the patients do not respond to the treatment. Genetics and lifestyle may affect the treatment results. The aims of this multidisciplinary collaboration are to identify (1 molecular signatures of prognostic value to help tailor treatment decisions to an individual likely to initiate TNF inhibitor therapy, followed by (2 lifestyle factors that support achievement of optimised treatment outcome. This report describes the establishment of a cohort that aims to obtain this information. Clinical data including lifestyle and treatment response and biological specimens (blood, faeces, urine, and, in IBD patients, intestinal biopsies are sampled prior to and while on TNF inhibitor therapy. Both hypothesis-driven and data-driven analyses will be performed according to pre-specified protocols including pathway analyses resulting from candidate gene expression analyses and global approaches (e.g., metabolomics, metagenomics, proteomics. The final purpose is to improve the lives of patients suffering from CIDs, by providing tools facilitating treatment selection and dietary recommendations likely to improve the clinical outcome.

  10. EFFECTS OF Β-ADRENOBLOCKERS ON MYOCARDIAL REMODELING, IMMUNO-INFLAMMATORY REACTIONS AND ENDOTHELIAL DYSFUNCTION IN PATIENTS WITH ISCHEMIC HEART DISEASE AND CHRONIC HEART FAILURE

    Directory of Open Access Journals (Sweden)

    A. N. Zakirova

    2015-12-01

    Full Text Available Aim. To assess the effect of β-adrenoblockers (BAB on myocardial remodeling, immuno-inflammatory reactions and endothelial dysfunction in patients with ischemic heart disease and chronic heart failure (CHF.Material and methods. 84 patients with ischemic CHF of II-IV functional class were involved in the study. They were randomized in two groups. The first group was presented with 43 patients receiving carvedilol in addition to standard therapy for 24 weeks; the second group was presented with 41patients receiving metoprolol. Echocardiography, 6-minute walk test were applied. Blood levels of primary and secondary lipid peroxidation (LP products, cytokines, endothelin-1 (ET-1, intercellular adhesive molecule (VCAM-1 were determined.Results. Both of BAB improved the clinical condition and physical working ability of patients with CHF. Carvedilol in comparison with metoprolol was more effective in myocardial remodeling prevention, inhibition of pro-inflammatory cytokines [tumor necrosis factor alpha (TNF-α, interleukins (IL-1β IL-6] and LP. Besides carvedilol increased in endothelium-dependent vasodilatation and reduced in ET-1 and VCAM-1 levels.Conclusion. Long-term carvedilol treatment has anti-inflammatory, antioxidant and endothelium-protective effects as well as improves haemodynamics. 

  11. Anti-Helicobacter pylori and Anti-Inflammatory Effects and Constituent Analysis of Modified Xiaochaihutang for the Treatment of Chronic Gastritis and Gastric Ulcer

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    Xin Chen

    2018-01-01

    Full Text Available Chronic gastritis and gastric ulcers are prevalent throughout the world and are considered to be a global health problem. Modified Xiaochaihutang (MXCHT prescription is broadly used in traditional medicine hospital for the treatment of gastritis. In order to assess the anti-Helicobacter pylori (H. pylori effect of MXCHT, agar diffusion method in vitro and fluid dilution method for the minimal inhibitory concentration (MIC were established. The anti-inflammatory effects were then evaluated using mouse ear edema model and rat paw edema model. The ethanol-induced gastric ulcer method was employed to verify the gastroprotective effect of active extracts in MXCHT. HPLC-TOF-MS/MS was used for analyzing the possible active constituents after oral administration of effective extracts in ethanol-induced gastric ulcer models. MXCHT and 4 different extracts of the bacterial inhibition diameter and MIC were dramatically decreased compared with control group, showing anti-Helicobacter pylori effects. High dose groups of MXCHT, water extract, EtOAc extract, and n-BuOH extract displayed significant anti-inflammatory effects in xylene-induced mouse ear edema model and carrageenan-induced rat paw edema model test. MXCHT and all active extracts exhibited gastroprotective activity and prevented gastric lesions induced by ethanol in rats. 4 prototype components and 4 metabolites were identified after oral administration of EtOAc extract. In addition, 6 prototype components and 6 metabolites were identified in n-BuOH extract. MXCHT, EtOAc extract, and n-BuOH extract demonstrate gastroprotective effects through anti-Helicobacter pylori and anti-inflammatory activities. Thus, this prescription may be a suitable natural source for the prevention and treatment of chronic gastritis and gastric ulcers.

  12. Chronic orbital inflammatory disease and optic neuropathy associated with long-term intranasal cocaine abuse: 2 cases and literature review

    NARCIS (Netherlands)

    Siemerink, Martin J.; Freling, Nicole J. M.; Saeed, Peerooz

    2017-01-01

    Orbital inflammatory disease and secondary optic neuropathy is a rare but devastating complication of long-term intranasal cocaine abuse. We describe 2 patients with a history of intranasal cocaine consumption who presented with subacute onset of unilateral vision loss from optic neuropathy and

  13. Progesterone therapy induces an M1 to M2 switch in microglia phenotype and suppresses NLRP3 inflammasome in a cuprizone-induced demyelination mouse model.

    Science.gov (United States)

    Aryanpour, Roya; Pasbakhsh, Parichehr; Zibara, Kazem; Namjoo, Zeinab; Beigi Boroujeni, Fatemeh; Shahbeigi, Saeed; Kashani, Iraj Ragerdi; Beyer, Cordian; Zendehdel, Adib

    2017-10-01

    Demyelination of the central nervous system (CNS) has been associated to reactive microglia in neurodegenerative disorders, such as multiple sclerosis (MS). The M1 microglia phenotype plays a pro-inflammatory role while M2 is involved in anti-inflammatory processes in the brain. In this study, CPZ-induced demyelination mouse model was used to investigate the effect of progesterone (PRO) therapy on microglia activation and neuro-inflammation. Results showed that progesterone therapy (CPZ+PRO) decreased neurological behavioral deficits, as demonstrated by significantly decreased escape latencies, in comparison to CPZ mice. In addition, CPZ+PRO caused a significant reduction in the mRNA expression levels of M1-markers (iNOS, CD86, MHC-II and TNF-α) in the corpus callosum region, whereas the expression of M2-markers (Trem-2, CD206, Arg-1 and TGF-β) was significantly increased, in comparison to CPZ mice. Moreover, CPZ+PRO resulted in a significant decrease in the number of iNOS + and Iba-1 + /iNOS + cells (M1), whereas TREM-2 + and Iba-1 + /TREM-2 + cells (M2) significantly increased, in comparison to CPZ group. Furthermore, CPZ+PRO caused a significant decrease in mRNA and protein expression levels of NLRP3 and IL-18 (~2-fold), in comparison to the CPZ group. Finally, CPZ+PRO therapy was accompanied with reduced levels of demyelination, compared to CPZ, as confirmed by immunofluorescence to myelin basic protein (MBP) and Luxol Fast Blue (LFB) staining, as well as transmission electron microscopy (TEM) analysis. In summary, we reported for the first time that PRO therapy causes polarization of M2 microglia, attenuation of M1 phenotype, and suppression of NLRP3 inflammasome in a CPZ-induced demyelination model of MS. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Differential local tissue permissiveness influences the final fate of GPR17‐expressing oligodendrocyte precursors in two distinct models of demyelination

    Science.gov (United States)

    Coppolino, Giusy T.; Marangon, Davide; Negri, Camilla; Menichetti, Gianluca; Fumagalli, Marta; Gelosa, Paolo; Dimou, Leda; Furlan, Roberto; Lecca, Davide

    2018-01-01

    Abstract Promoting remyelination is recognized as a novel strategy to foster repair in neurodegenerative demyelinating diseases, such as multiple sclerosis. In this respect, the receptor GPR17, recently emerged as a new target for remyelination, is expressed by early oligodendrocyte precursors (OPCs) and after a certain differentiation stage it has to be downregulated to allow progression to mature myelinating oligodendrocytes. Here, we took advantage of the first inducible GPR17 reporter mouse line (GPR17‐iCreERT2xCAG‐eGFP mice) allowing to follow the final fate of GPR17+ cells by tamoxifen‐induced GFP‐labeling to unveil the destiny of these cells in two demyelination models: experimental autoimmune encephalomyelitis (EAE), characterized by marked immune cell activation and inflammation, and cuprizone induced demyelination, where myelin dysfunction is achieved by a toxic insult. In both models, demyelination induced a strong increase of fluorescent GFP+ cells at damaged areas. However, only in the cuprizone model reacting GFP+ cells terminally differentiated to mature oligodendrocytes, thus contributing to remyelination. In EAE, GFP+ cells were blocked at immature stages and never became myelinating oligodendrocytes. We suggest these strikingly distinct fates be due to different permissiveness of the local CNS environment. Based on previously reported GPR17 activation by emergency signals (e.g., Stromal Derived Factor‐1), we propose that a marked inflammatory milieu, such as that reproduced in EAE, induces GPR17 overactivation resulting in impaired downregulation, untimely and prolonged permanence in OPCs, leading, in turn, to differentiation blockade. Combined treatments with remyelinating agents and anti‐inflammatory drugs may represent new potential adequate strategies to halt neurodegeneration and foster recovery. PMID:29424466

  15. In myalgic encephalomyelitis/chronic fatigue syndrome, increased autoimmune activity against 5-HT is associated with immuno-inflammatory pathways and bacterial translocation.

    Science.gov (United States)

    Maes, Michael; Ringel, Karl; Kubera, Marta; Anderson, George; Morris, Gerwyn; Galecki, Piotr; Geffard, Michel

    2013-09-05

    Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is accompanied by activation of immuno-inflammatory pathways, increased bacterial translocation and autoimmune responses to serotonin (5-HT). Inflammation is known to damage 5-HT neurons while bacterial translocation may drive autoimmune responses. This study has been carried out to examine the autoimmune responses to 5-HT in ME/CFS in relation to inflammation and bacterial translocation. We examined 5-HT antibodies in 117 patients with ME/CFS (diagnosed according to the centers for disease control and prevention criteria, CDC) as compared with 43 patients suffering from chronic fatigue (CF) but not fulfilling the CDC criteria and 35 normal controls. Plasma interleukin-1 (IL-1), tumor necrosis factor (TNF)α, neopterin and the IgA responses to Gram-negative bacteria were measured. Severity of physio-somatic symptoms was measured using the fibromyalgia and chronic fatigue syndrome rating scale (FF scale). The incidence of positive autoimmune activity against 5-HT was significantly higher (pfatigue, neurocognitive and autonomic symptoms, sadness and a flu-like malaise. The results show that, in ME/CFS, increased 5-HT autoimmune activity is associated with activation of immuno-inflammatory pathways and increased bacterial translocation, factors which are known to play a role in the onset of autoimmune reactions. 5-HT autoimmune activity could play a role in the pathophysiology of ME/CFS and the onset of physio-somatic symptoms. These results provide mechanistic support for the notion that ME/CFS is a neuro-immune disorder. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. IL-1ra anti-inflammatory cytokine polymorphism is associated with risk of gastric cancer and chronic gastritis in a Brazilian population, but the TNF-β pro-inflammatory cytokine is not.

    Science.gov (United States)

    Oliveira, J Garcia; Duarte, M Cristina; Silva, A Elizabete

    2012-07-01

    Genetic polymorphisms in genes that codify inflammatory cytokines have been associated with gastric carcinogenesis. This study evaluated polymorphisms IL-1RN VNTR and TNFB+252A/G in a population from Southeast Brazil with regard to the risk of chronic gastritis and gastric cancer and the presence of an association of gastric lesions with risk factors such as gender, age, smoking, drinking and Helicobacter pylori infection. In this case-control study, polymorphism at IL-1RN VNTR was investigated using the allele-specific polymerase chain reaction method, while the polymerase chain reaction-restriction fragment length polymorphism technique was used to identify the TNFB+252A/G genotype in 675 Brazilian individuals [229 with chronic gastritis (CG), 200 with gastric cancer (GC) and 246 healthy individuals as controls (C)]. Multiple logistic regression analysis (log-additive, dominant, and recessive models) have not showed association of the genotype frequencies for the SNP TNFB + 252A/G with risk of CG or GC. However, as for IL-1RN VNTR it was observed significant differences in all three analysis models, with higher values of OR in recessive model, both in the GC group (OR = 3.04, 95% CI = 1.41-6.56, p cancer and precancerous lesions in the Southeast Brazilian population, reinforcing the importance of host genetic factors in the susceptibility to gastric cancer and the participation of cytokines in both the inflammation and the carcinogenic process.

  17. Getting an Insight into the Complexity of Major Chronic Inflammatory and Degenerative Diseases: A Potential New Systemic Approach to Their Treatment.

    Science.gov (United States)

    Biava, Pier M; Norbiato, Guido

    2015-01-01

    As the modern society is troubled by multi-factorial diseases, research has been conducted on complex realities including chronic inflammation, cancer, obesity, HIV infection, metabolic syndrome and its detrimental cardiovascular complications as well as depression and other brain disorders. Deterioration of crucial homeostatic mechanisms in such diseases invariably results in activation of inflammatory mediators, chronic inflammation, loss in immunological function, increased susceptibility to diseases, alteration of metabolism, decrease of energy production and neuro-cognitive decline. Regulation of genes expression by epigenetic code is the dominant mechanism for the transduction of environmental inputs, such as stress and inflammation to lasting physiological changes. Acute and chronic stress determines DNA methylation and histone modifications in brain regions which may contribute to neuro-degenerative disorders. Nuclear glucocorticoids receptor interacts with the epigenoma resulting in a cortisol resistance status associated with a deterioration of the metabolic and immune functions. Gonadal steroids receptors have a similar capacity to produce epigenomic reorganization of chromatine structure. Epigenomic-induced reduction in immune cells telomeres length has been observed in many degenerative diseases, including all types of cancer. The final result of these epigenetic alterations is a serious damage to the neuro-endocrine-immune-metabolic adaptive systems. In this study, we propose a treatment with stem cells differentiation stage factors taken from zebrafish embryos which are able to regulate the genes expression of normal and pathological stem cells in a different specific way.

  18. Plasma proteomics shows an elevation of the anti-inflammatory protein APOA-IV in chronic equine laminitis

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    Steelman Samantha M

    2012-09-01

    Full Text Available Abstract Background Equine laminitis is a devastating disease that causes severe pain in afflicted horses and places a major economic burden on the horse industry. In acute laminitis, the disintegration of the dermal-epidermal junction can cause the third phalanx to detach from the hoof wall, leaving the horse unable to bear weight on the affected limbs. Horses that survive the acute phase transition into a chronic form of laminitis, which is often termed “founder”. Some evidence suggests that chronic laminar inflammation might be associated with alterations in the endocrine and immune systems. We investigated this broad hypothesis by using DIGE to assess global differences in the plasma proteome between horses with chronic laminitis and controls. Results We identified 16 differentially expressed proteins; the majority of these were involved in the interrelated coagulation, clotting, and kininogen cascades. Clinical testing of functional coagulation parameters in foundered horses revealed a slight delay in prothrombin (PT clotting time, although most other indices were within normal ranges. Upregulation of the intestinal apolipoprotein APOA-IV in horses with chronic laminitis was confirmed by western blot. Conclusions Our results support the hypothesis that localized laminar inflammation may be linked to systemic alterations in immune regulation, particularly in the gastrointestinal system. Gastrointestinal inflammation has been implicated in the development of acute laminitis but has not previously been associated with chronic laminitis.

  19. BUILING THE INFLAMMATORY PROCESS IN BRONCHES AT THE PHASE OF PATIENTS REHABILITATION WITH PROFESSIONAL CHRONIC OBSTRUCTIVE LUNG DISEASE

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    Раиса Васильевна Гордеева

    2017-10-01

    Conclusions. In case of exacerbation of occupational COPD at the stage of rehabilitation for rapid relief of inflammation of the mucosa of respiratory tract, it is advisable to prescribe Miramistin inhalation, laser therapy and SMC- phoresis of Miramistin. The proposed sequence of the application of physical factors contributes to the recovery of the protection of the mucosa of the respiratory tract and as a result an anti-inflammatory effect is manifested.

  20. The Effect of Topical Amphotericin B on Inflammatory Markers in Patients With Chronic Rhinosinusitis: A Multicenter Randomized Controlled Study

    NARCIS (Netherlands)

    Ebbens, Fenna A.; Georgalas, Christos; Luiten, Silvia; van Drunen, Cornelis M.; Badia, Lydia; Scadding, Glenis K.; Hellings, Peter W.; Jorissen, Mark; Mullol, Joaquim; Cardesin, Alda; Bachert, Claus; van Zele, Thibaut P. J.; Lund, Valerie J.; Fokkens, W. J.

    2009-01-01

    Background: It has been suggested that an exaggerated immune response to fungi is crucial in the pathogenesis of chronic rhinosinusitis (CRS). Based on this rationale, the use of topical antifungals (amphotericin B) has been advocated. Studies on its clinical effectiveness are, however,

  1. Primary skeletal muscle myoblasts from chronic heart failure patients exhibit loss of anti-inflammatory and proliferative activity

    NARCIS (Netherlands)

    Sente, T.; Berendoncks, A.M. Van; Jonckheere, A.I.; Rodenburg, R.J.T.; Lauwers, P.; Hoof, V. Van; Wouters, A.; Lardon, F.; Hoymans, V.Y.; Vrints, C.J.

    2016-01-01

    BACKGROUND: Peripheral skeletal muscle wasting is a common finding with adverse effects in chronic heart failure (HF). Whereas its clinical relevance is beyond doubt, the underlying pathophysiological mechanisms are not yet fully elucidated. We aimed to introduce and characterize the primary culture

  2. RNase L mediated protection from virus induced demyelination.

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    Derek D C Ireland

    2009-10-01

    Full Text Available IFN-alpha/beta plays a critical role in limiting viral spread, restricting viral tropism and protecting mice from neurotropic coronavirus infection. However, the IFN-alpha/beta dependent mechanisms underlying innate anti-viral functions within the CNS are poorly understood. The role of RNase L in viral encephalomyelitis was explored based on its functions in inhibiting translation, inducing apoptosis, and propagating the IFN-alpha/beta pathway through RNA degradation intermediates. Infection of RNase L deficient (RL(-/- mice with a sub-lethal, demyelinating mouse hepatitis virus variant revealed that the majority of mice succumbed to infection by day 12 p.i. However, RNase L deficiency did not affect overall control of infectious virus, or diminish IFN-alpha/beta expression in the CNS. Furthermore, increased morbidity and mortality could not be attributed to altered proinflammatory signals or composition of cells infiltrating the CNS. The unique phenotype of infected RL(-/- mice was rather manifested in earlier onset and increased severity of demyelination and axonal damage in brain stem and spinal cord without evidence for enhanced neuronal infection. Increased tissue damage coincided with sustained brain stem infection, foci of microglia infection in grey matter, and increased apoptotic cells. These data demonstrate a novel protective role for RNase L in viral induced CNS encephalomyelitis, which is not reflected in overall viral control or propagation of IFN-alpha/beta mediated signals. Protective function is rather associated with cell type specific and regional restriction of viral replication in grey matter and ameliorated neurodegeneration and demyelination.

  3. Myalgic Encephalomyelitis (ME), Chronic Fatigue Syndrome (CFS), and Chronic Fatigue (CF) are distinguished accurately: results of supervised learning techniques applied on clinical and inflammatory data.

    Science.gov (United States)

    Maes, Michael; Twisk, Frank N M; Johnson, Cort

    2012-12-30

    There is much debate on the diagnostic classification of Myalgic Encephalomyelitis (ME), Chronic Fatigue Syndrome (CFS) and chronic fatigue (CF). Post-exertional malaise (PEM) is stressed as a key feature. This study examines whether CF and CFS, with and without PEM, are distinct diagnostic categories. Fukuda's criteria were used to diagnose 144 patients with chronic fatigue and identify patients with CFS and CF, i.e. those not fulfilling the Fukuda's criteria. PEM was rated by means of a scale with defined scale steps between 0 and 6. CFS patients were divided into those with PEM lasting more than 24h (labeled: ME) and without PEM (labeled: CFS). The 12-item Fibromyalgia and Chronic Fatigue Syndrome (FF) Rating Scale was used to measure severity of illness. Plasma interleukin-1 (IL-1), tumor necrosis factor (TNF)α, and lysozyme, and serum neopterin were employed as external validating criteria. Using fatigue, a subjective feeling of infection and PEM we found that ME, CFS, and CF were distinct categories. Patients with ME had significantly higher scores on concentration difficulties and a subjective experience of infection, and higher levels of IL-1, TNFα, and neopterin than patients with CFS. These biomarkers were significantly higher in ME and CFS than in CF patients. PEM loaded highly on the first two factors subtracted from the data set, i.e. "malaise-sickness" and "malaise-hyperalgesia". Fukuda's criteria are adequate to make a distinction between ME/CFS and CF, but ME/CFS patients should be subdivided into ME (with PEM) and CFS (without PEM). Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  4. Gene-expression analysis of matrix metalloproteinases 1 and 2 and their tissue inhibitors in chronic periapical inflammatory lesions.

    Science.gov (United States)

    Hadziabdic, Naida; Kurtovic-Kozaric, Amina; Pojskic, Naris; Sulejmanagic, Nedim; Todorovic, Ljubomir

    2016-03-01

    Periapical inflammatory lesions have been investigated previously, but understanding of pathogenesis of these lesions (granulomas and radicular cysts) at the molecular level is still questionable. Matrix metalloproteinases (MMPs) are enzymes involved in the development of periapical pathology, specifically inflammation and tissue destruction. To elucidate pathogenesis of periapical granulomas and radicular cysts, we undertook a detailed analysis of gene expression of MMP-1, MMP-2 and their tissue inhibitors, TIMP-1 and TIMP-2. A total of 149 samples were analyzed using real-time PCR (59 radicular cysts, 50 periapical granulomas and 40 healthy gingiva samples as controls) for expression of MMP-1, MMP-2, TIMP-1 and TIMP-2 genes. The determination of best reference gene for expression analysis of periapical lesions was done using a panel of 12 genes. We have shown that β-actin and GAPDH are not the most stable reference controls for gene expression analysis of inflammatory periapical tissues and healthy gingiva. The most suitable reference gene was determined to be SDHA (a succinate dehydrogenase complex, subunit A, flavoprotein [Fp]). We found that granulomas (n = 50) and radicular cysts (n = 59) exhibited significantly higher expression of all four examined genes, MMP-1, MMP-2, TIMP-1, and TIMP-2, when compared to healthy gingiva (n = 40; P periapical inflammatory lesions. Since the abovementioned markers were not differentially expressed in periapical granulomas and radicular cysts, the challenge of finding the genetic differences between the two lesions still remains. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Expression of Annexin-A1 and Galectin-1 Anti-Inflammatory Proteins and mRNA in Chronic Gastritis and Gastric Cancer

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    Yvana Cristina Jorge

    2013-01-01

    Full Text Available Objective. The anti-inflammatory proteins annexin-A1 and galectin-1 have been associated with tumor progression. This scenario prompted us to investigate the relationship between the gene and protein expression of annexin-A1 (ANXA1/AnxA1 and galectin-1 (LGALS1/Gal-1 in an inflammatory gastric lesion as chronic gastritis (CG and gastric adenocarcinoma (GA and its association with H. pylori infection. Methods. We analyzed 40 samples of CG, 20 of GA, and 10 of normal mucosa (C by the quantitative real-time PCR (qPCR technique and the immunohistochemistry assay. Results. High ANXA1 mRNA expression levels were observed in 90% (36/40 of CG cases (mean relative quantification RQ = 4.26 ± 2.03 and in 80% (16/20 of GA cases (mean RQ = 4.38 ± 4.77. However, LGALS1 mRNA levels were high (mean RQ = 2.44 ± 3.26 in 60% (12/20 of the GA cases, while low expression was found in CG (mean RQ = 0.43±3.13; P<0.01. Normal mucosa showed modest immunoreactivity in stroma but not in epithelium, while stroma and epithelium displayed an intense immunostaining in CG and GA for both proteins. Conclusion. These results have provided evidence that galectin-1 and mainly annexin-A1 are overexpressed in both gastritis and gastric cancer, suggesting a strong association of these proteins with chronic gastric inflammation and carcinogenesis.

  6. L-Menthone confers antidepressant-like effects in an unpredictable chronic mild stress mouse model via NLRP3 inflammasome-mediated inflammatory cytokines and central neurotransmitters.

    Science.gov (United States)

    Xue, Jinsong; Li, Hongyan; Deng, Xueyang; Ma, Zhanqiang; Fu, Qiang; Ma, Shiping

    2015-07-01

    L-Menthone (MTN) is a Chinese old remedy extracted from the genus Mentha. It has been widely used as a cooling agent and a counterirritant for pain relief, although its antidepressant-like effects have not yet been reported. The present study was designed to investigate whether MTN confers an antidepressant-like effect in mice exposed to unpredictable chronic mild stress (UCMS) and to explore its potential mechanisms. The effects of MTN on mouse behavioral changes were investigated in our study. We determined the levels of the nucleotide binding, oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, inflammatory cytokines and neurotransmitters in the hippocampus of mice. Behavioral tests, including the sucrose preference test (SPT), open field test (OFT), forced swimming test (FST) and tail suspension test (TST) revealed that MTN (15 and 30mg/kg) treatments for 3weeks alleviated the depression symptoms of UCMS in mice. Mice receiving MTN treatments exhibited reduced levels of NLRP3 and caspase-1. Moreover, MTN treatments reversed the UCMS-induced alterations in the concentrations of neurotransmitter norepinephrine (NE) and serotonin (5-HT) and inhibited the expression of pro-inflammatory cytokines (PIC) interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in the hippocampus of mice. Taken together, our findings suggested that MTN may play a potential antidepressant-like role in the UCMS mouse model by regulating the NLRP3 inflammasome and mediating inflammatory cytokines and central neurotransmitters, which together provide insight towards the development of novel therapeutic treatments for depression. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. [Treatment with non-steroidal anti-inflammatory drugs in patients with amicrobial chronic prostato-vesiculitis: transrectal ultrasound and seminal findings].

    Science.gov (United States)

    Vicari, E; La Vignera, S; Battiato, C; Arancio, A

    2005-03-01

    The aim of this paper was to evaluate the efficacy (0= none; 3= fully) of the treatment with nonsteroidal anti-inflammatory (NSAI) drugs on (a) gland post-inflammatory echopattern, by transrectal ultrasound (TRUS); (b) seminal cytologic (WBC concentration and spermiophagies) and (c) >2 physicochemical inflammatory parameters in patients with chronic amicrobial prostato-vesiculitis (PV). Thirty-five patients with PV received NSAI drugs in the following intermittently steps (over a 3-month period): 1) Pygeum 100 mg twice a day for 14 consecutive days per month; 2) flavoxate-propyphenazone 400 mg twice a day plus Serratiopeptidase 10 000 U twice a day for the subsequent 14 days per month. All patients underwent semen analysis and TRUS scans in the pre-treatment and after 3 months of therapy. The fully (a+b+c) efficacy rate, through an improvement of TRUS prostatic or vesicular echopattern in 37.1% and 22.8% respectively, was higher than that registered with an improvement of only 1 or 2 endpoints. Altogether, the following TRUS findings showed reductions (range 25-40%): prostate volume and hypochogenicity (51.4%); vesicular antero-posterior diameter (APD) in the 43.5% and 28.6% of the uni- and bilateral PV respectively; vesicular wall tickness (25%); unilateral vesicular honeycomb aspect (36%). No efficacy, mainly related to immodified TRUS prostatic or vesicular echopattern in 51.4% and 65.7% respectively, was observed on: areas of prostatic hyperechogenicity; peri-prostatic venous congestion; vesicular APD 21 mm (with honeycomb aspect). In PV patients, the treatment with NSAI compounds was effective when it was enable to produce multiple positive effects, mainly through TRUS changes.

  8. Association of pentraxin and high-sensitive C-reactive protein as inflammatory biomarkers in patients with chronic periodontitis and peripheral arterial disease.

    Science.gov (United States)

    Boyapati, Ramanarayana; Chinthalapani, Srikanth; Ramisetti, Arpita; Salavadhi, Shyam Sunder; Ramachandran, Radhika

    2018-01-01

    Inflammation is a common feature of both peripheral artery disease (PAD) and periodontal disease. The aim of this study is to evaluate the relationship between PAD and periodontal disease by examining the levels of inflammatory cytokines, pentraxin-3 (PTX-3), and high-sensitive C-reactive protein from serum. A total of 50 patients were included in this cross-sectional study. Patients were divided into two groups: those with PAD (test group) and those with the non-PAD group (control group) based on ankle-brachial index values. Periodontal examinations and biochemical analysis for PTX-3 and high-sensitive C-reactive protein were performed to compare the two groups. All the obtained data were sent for statistical analyses using SPSS version 18. In the clinical parameters, there is statistically significant difference present between plaque index, clinical attachment loss, and periodontal inflammatory surface area with higher mean values in patients with PAD having periodontitis. There is statistical significant ( P C-reactive protein (hs-CRP), and PTX-3. PTX-3 and acute-phase cytokine such as hs-CRP can be regarded as one of the best indicators to show the association between the PAD and periodontitis followed by hs-CRP, TC, very LDL (VLDL), and LDL. However, high-density lipoprotein (HDL) is a poor indicator for its association with chronic periodontitis and PAD.

  9. Insights into iron and nuclear factor-kappa B (NF-kappaB) involvement in chronic inflammatory processes in peritoneal endometriosis.

    Science.gov (United States)

    Defrère, Sylvie; González-Ramos, Reinaldo; Lousse, Jean-Christophe; Colette, Sébastien; Donnez, Olivier; Donnez, Jacques; Van Langendonckt, Anne

    2011-08-01

    Endometriosis is a chronic pelvic inflammatory process. Local inflammation is known to play a role in pain and infertility associated with the disease, and may be extensively involved in molecular and cellular processes leading to endometriosis development. In this review, we focus on two inflammatory mediators clearly implicated in the pathogenesis of endometriosis, iron and NF-kappaB, and their potential association. Iron is essential for all living organisms, but excess iron results in toxicity and is linked to pathological disorders. In endometriosis patients, iron overload has been demonstrated in the different compartments of the peritoneal cavity (peritoneal fluid, endometriotic lesions, peritoneum and macrophages). This iron overload affects numerous mechanisms involved in endometriosis development. Moreover, iron can generate free radical species able to react with a wide range of cellular constituents, inducing cellular damage. Overproduction of reactive oxygen species also impairs cellular function by altering gene expression via regulation of redox-sensitive transcription factors such as NF-kappaB, which is clearly implicated in endometriosis. Indeed, NF-kappaB is activated in endometriotic lesions and peritoneal macrophages of endometriosis patients, which stimulates synthesis of proinflammatory cytokines, generating a positive feedback loop in the NF-kappaB pathway. NF-kappaB-mediated gene transcription promotes a variety of processes, including endometriotic lesion establishment, maintenance and development. In conclusion, iron and NF-kappaB appear to be linked and both are clearly involved in endometriosis development, making these pathways an attractive target for future treatment and prevention of this disease.

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

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    Xiaoling Bu

    2015-01-01

    Full Text Available 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.

  11. Hyper-activated pro-inflammatory CD16 monocytes correlate with the severity of liver injury and fibrosis in patients with chronic hepatitis B.

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    Ji-Yuan Zhang

    Full Text Available BACKGROUND: Extensive mononuclear cell infiltration is strongly correlated with liver damage in patients with chronic hepatitis B virus (CHB infection. Macrophages and infiltrating monocytes also participate in the development of liver damage and fibrosis in animal models. However, little is known regarding the immunopathogenic role of peripheral blood monocytes and intrahepatic macrophages. METHODOLOGY/PRINCIPAL FINDINGS: The frequencies, phenotypes, and functions of peripheral blood and intrahepatic monocyte/macrophage subsets were analyzed in 110 HBeAg positive CHB patients, including 32 immune tolerant (IT carriers and 78 immune activated (IA patients. Liver biopsies from 20 IA patients undergoing diagnosis were collected for immunohistochemical analysis. IA patients displayed significant increases in peripheral blood monocytes and intrahepatic macrophages as well as CD16(+ subsets, which were closely associated with serum alanine aminotransferase (ALT levels and the liver histological activity index (HAI scores. In addition, the increased CD16(+ monocytes/macrophages expressed higher levels of the activation marker HLA-DR compared with CD16(- monocytes/macrophages. Furthermore, peripheral blood CD16(+ monocytes preferentially released inflammatory cytokines and hold higher potency in inducing the expansion of Th17 cells. Of note, hepatic neutrophils also positively correlated with HAI scores. CONCLUSIONS: These distinct properties of monocyte/macrophage subpopulations participate in fostering the inflammatory microenvironment and liver damage in CHB patients and further represent a collaborative scenario among different cell types contributing to the pathogenesis of HBV-induced liver disease.

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

    Science.gov (United States)

    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

  13. Alteration of Inflammatory Mediators in the Upper and Lower Airways under Chronic Intermittent Hypoxia: Preliminary Animal Study

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    Eun Jung Lee

    2017-01-01

    Full Text Available Purpose. We hypothesized that CIH may affect the upper airway immune system and aimed to verify whether CIH can induce airway inflammation in a murine obstructive sleep apnea (OSA model. Methods. C57BL6 male mice were exposed to intermittent hypoxia (CIH group; 5 ~ 21% FiO2, 120 sec cycles, 12 h/d, n=6 or room air (Sham group, n=6 for up to 4 weeks in identical chambers. Nasal and lung tissues and lavage fluid were collected and analyzed by multiplex assay. Lung lavage fluid was also utilized for FACS analysis to determine eosinophil count. Results. We determined the protein level of 24 different cytokines, chemokines, and inflammatory mediators. Among various cytokines, levels of IL-1α, IL-1β, IL-4, IL-6, and IL-13 were significantly elevated in nose or lung tissue from the CIH group. In addition, MCP-1 and periostin were elevated in nose and lung tissue and lavage fluid from the CIH group. Conclusions. CIH for 4 weeks altered the levels of inflammatory mediators in both the nose and lungs of mouse model. We suggest that the airway immune system may be deteriorated by CIH and allergic inflammation in the upper or lower airway could be worsened by sleep apnea.

  14. Non-steroidal anti-inflammatory drugs (NSAIDs) for chronic non-cancer pain in children and adolescents

    OpenAIRE

    Eccleston, Christopher; Cooper, Tess E.; Fisher, Emma; Anderson, Brian; Wilkinson, Nick M. R.

    2017-01-01

    Background Pain is a common feature of childhood and adolescence around the world, and for many young people, that pain is chronic. The World Health Organization guidelines for pharmacological treatments for children's persisting pain acknowledge that pain in children is a major public health concern of high significance in most parts of the world. While in the past pain was largely dismissed and was frequently left untreated, views on children's pain have changed over time, and relief of pai...

  15. High frequency of chronic bacterial and non-inflammatory prostatitis in infertile patients with prostatitis syndrome plus irritable bowel syndrome.

    OpenAIRE

    Enzo Vicari; Sandro La Vignera; Domenico Arcoria; Rosita Condorelli; Lucia O Vicari; Roberto Castiglione; Andrea Mangiameli; Aldo E Calogero

    2011-01-01

    Background Although prostatitis syndrome (PS) and irritable bowel syndrome (IBS) are common disorders, information on the prevalence of IBS in infertile patients with PS is relatively scanty. Therefore, this study was undertaken to estimate the frequency of PS and IBS and to evaluate the prevalence of the various diagnostic categories of prostatitis. Methodology/Principal Findings This study enrolled 152 patients with PS, diagnosed by the NIH-Chronic Prostatitis Symptom Index (NIH-CPSI) in an...

  16. Immunological Demyelination Triggers Macrophage/Microglial Cells Activation without Inducing Astrogliosis

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    Frank Cloutier

    2013-01-01

    Full Text Available The glial scar formed by reactive astrocytes and axon growth inhibitors associated with myelin play important roles in the failure of axonal regeneration following central nervous system (CNS injury. Our laboratory has previously demonstrated that immunological demyelination of the CNS facilitates regeneration of severed axons following spinal cord injury. In the present study, we evaluate whether immunological demyelination is accompanied with astrogliosis. We compared the astrogliosis and macrophage/microglial cell responses 7 days after either immunological demyelination or a stab injury to the dorsal funiculus. Both lesions induced a strong activated macrophage/microglial cells response which was significantly higher within regions of immunological demyelination. However, immunological demyelination regions were not accompanied by astrogliosis compared to stab injury that induced astrogliosis which extended several millimeters above and below the lesions, evidenced by astroglial hypertrophy, formation of a glial scar, and upregulation of intermediate filaments glial fibrillary acidic protein (GFAP. Moreover, a stab or a hemisection lesion directly within immunological demyelination regions did not induced astrogliosis within the immunological demyelination region. These results suggest that immunological demyelination creates a unique environment in which astrocytes do not form a glial scar and provides a unique model to understand the putative interaction between astrocytes and activated macrophage/microglial cells.

  17. [Demyelinating disease and vaccination of the human papillomavirus].

    Science.gov (United States)

    Álvarez-Soria, M Josefa; Hernández-González, Amalia; Carrasco-García de León, Sira; del Real-Francia, M Ángeles; Gallardo-Alcañiz, M José; López-Gómez, José L

    2011-04-16

    Primary prevention by prophylactic vaccination against the major cause of cervical cancer, the carcinogenic human papillomavirus (HPV) types 16 and 18, is now available worldwide. Postlicensure adverse neurological effects have been described. The studies realized after the license are descriptive and limited by the difficulty to obtain the information, despite most of the statistical indexes show that the adverse effects by the vaccine of the HPV are not upper compared with other vaccines, the substimation must be considered. We describe the cases of four young women that developed demyelinating disease after the vaccination of the HPV, with a rank of time between the administration of the dose and the development of the clinical of seven days to a month, with similar symptoms with the successive doses. We have described six episodes coinciding after the vaccination. Have been described seizures, autoimmune disorders such as Guillain-Barre syndrome, transverse myelitis, or motor neuron disease, probably adverse effects following immunization by HPV vaccine. So we suggest that vaccine may trigger an immunological mechanism leading to demyelinating events, perhaps in predisposed young.

  18. Influence of type I IFN signaling on anti-MOG antibody-mediated demyelination

    DEFF Research Database (Denmark)

    Berg, Carsten Tue; Khorooshi, Reza M. H.; Asgari, Nasrin

    2017-01-01

    Background Antibodies with specificity for myelin oligodendrocyte glycoprotein (MOG) are implicated in multiple sclerosis and related diseases. The pathogenic importance of anti-MOG antibody in primary demyelinating pathology remains poorly characterized. Objective The objective of this study...... is to investigate whether administration of anti-MOG antibody would be sufficient for demyelination and to determine if type I interferon (IFN) signaling plays a similar role in anti-MOG antibody-mediated pathology, as has been shown for neuromyelitis optica-like pathology. Methods Purified IgG2a monoclonal anti...... demyelination in wild-type and IFNAR1-KO mice. Conclusions Anti-MOG antibody and complement was sufficient to induce callosal demyelination, and pathology was dependent on type I IFN. Induction of EAE in IFNAR1-KO mice overcame the dependence on type I IFN for anti-MOG and complement-mediated demyelination....

  19. Nitric oxide-heat shock protein axis in menopausal hot flushes: neglected metabolic issues of chronic inflammatory diseases associated with deranged heat shock response.

    Science.gov (United States)

    Miragem, Antônio Azambuja; Homem de Bittencourt, Paulo Ivo

    2017-09-01

    Although some unequivocal underlying mechanisms of menopausal hot flushes have been demonstrated in animal models, the paucity of similar approaches in humans impedes further mechanistic outcomes. Human studies might show some as yet unexpected physiological mechanisms of metabolic adaptation that permeate the phase of decreased oestrogen levels in both symptomatic and asymptomatic women. This is particularly relevant because both the severity and time span of hot flushes are associated with increased risk of chronic inflammatory disease. On the other hand, oestrogen induces the expression of heat shock proteins of the 70 kDa family (HSP70), which are anti-inflammatory and cytoprotective protein chaperones, whose expression is modulated by different types of physiologically stressful situations, including heat stress and exercise. Therefore, lower HSP70 expression secondary to oestrogen deficiency increases cardiovascular risk and predisposes the patient to senescence-associated secretory phenotype (SASP) that culminates in chronic inflammatory diseases, such as obesities, type 2 diabetes, neuromuscular and neurodegenerative diseases. This review focuses on HSP70 and its accompanying heat shock response (HSR), which is an anti-inflammatory and antisenescent pathway whose intracellular triggering is also oestrogen-dependent via nitric oxide (NO) production. The main goal of the manuscript was to show that the vasomotor symptoms that accompany hot flushes may be a disguised clue for important neuroendocrine alterations linking oestrogen deficiency to the anti-inflammatory HSR. Results from our own group and recent evidence on hypothalamic control of central temperature guided a search on PubMed and Google Scholar websites. Oestrogen elicits rapid production of the vasodilatory gas NO, a powerful activator of HSP70 expression. Whence, part of the protective effects of oestrogen over cardiovascular and neuroendocrine systems is tied to its capacity of inducing the NO

  20. Phosphatidylcholine 36:1 concentration decreases along with demyelination in the cuprizone animal model and post-mortem of multiple sclerosis brain tissue.

    Science.gov (United States)

    Trépanier, Marc-Olivier; Hildebrand, Kayla D; Nyamoya, Stella D; Amor, Sandra; Bazinet, Richard P; Kipp, Markus

    2018-03-25

    Multiple sclerosis (MS) is a demyelinating and inflammatory disease. Myelin is enriched in lipids, and more specifically, oleic acid. The goal of this study was to evaluate the concentration of oleic acid following demyelination and remyelination in the cuprizone model, test if these changes occurred in specific lipid species, and whether differences in the cuprizone model correlate with changes observed in post-mortem human brains. Eight-week-old C57Bl/6 mice were fed a 0.2% cuprizone diet for 5 weeks and some animals allowed to recover for 11 days. Demyelination, inflammation, and lipid concentrations were measured in the corpus callosum. Standard fatty acid techniques and liquid chromatography combined with tandem mass spectrometry were performed to measure concentrations of fatty acids in total brain lipids and a panel of lipid species within the phosphatidylcholine (PC). Similar measurements were conducted in post-mortem brain tissues of MS patients and were compared to healthy controls. Five weeks of cuprizone administration resulted in demyelination followed by significant remyelination after 11 days of recovery. Compared to control, oleic acid was decreased after 5 weeks of cuprizone treatment and increased during the recovery phase. This decrease in oleic acid was associated with a specific decrease in the PC 36:1 pool. Similar results were observed in human post-mortem brains. Decreases in myelin content in the cuprizone model was accompanied with decreases in oleic acid concentration and is associated with PC 36:1 suggesting that specific lipids could be a potential biomarker for myelin degeneration. The biological relevance of oleic acid for disease progression remains to be verified. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  1. Nonantibiotic macrolides restore airway macrophage phagocytic function with potential anti-inflammatory effects in chronic lung diseases.

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    Hodge, Sandra; Tran, Hai B; Hamon, Rhys; Roscioli, Eugene; Hodge, Greg; Jersmann, Hubertus; Ween, Miranda; Reynolds, Paul N; Yeung, Arthur; Treiberg, Jennifer; Wilbert, Sibylle

    2017-05-01

    We reported defective efferocytosis associated with cigarette smoking and/or airway inflammation in chronic lung diseases, including chronic obstructive pulmonary disease, severe asthma, and childhood bronchiectasis. We also showed defects in phagocytosis of nontypeable Haemophilus influenzae (NTHi), a common colonizer of the lower airway in these diseases. These defects could be substantially overcome with low-dose azithromycin; however, chronic use may induce bacterial resistance. The aim of the present study was therefore to investigate two novel macrolides-2'-desoxy-9-(S)-erythromycylamine (GS-459755) and azithromycin-based 2'-desoxy molecule (GS-560660)-with significantly diminished antibiotic activity against Staphylococcus aureus , Streptococcus pneumonia , Moraxella catarrhalis , and H. influenzae We tested their effects on efferocytosis, phagocytosis of NTHi, cell viability, receptors involved in recognition of apoptotic cells and/or NTHi (flow cytometry), secreted and cleaved intracellular IL-1β (cytometric bead array, immunofluorescence/confocal microscopy), and nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) using primary alveolar macrophages and THP-1 macrophages ± 10% cigarette smoke extract. Dose-response experiments showed optimal prophagocytic effects of GS-459755 and GS-560660 at concentrations of 0.5-1 µg/ml compared with our findings with azithromycin. Both macrolides significantly improved phagocytosis of apoptotic cells and NTHi (e.g., increases in efferocytosis and phagocytosis of NTHi: GS-459755, 23 and 22.5%, P = 0.043; GS-560660, 23.5 and 22%, P = 0.043, respectively). Macrophage viability remained >85% following 24 h exposure to either macrolide at concentrations up to 20 µg/ml. Secreted and intracellular-cleaved IL-1β was decreased with both macrolides with no significant changes in recognition molecules c-mer proto-oncogene tyrosine kinase; scavenger receptor class A, member 1; Toll

  2. Neurodevelopmental effects of chronic exposure to elevated levels of pro-inflammatory cytokines in a developing visual system

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    Ruthazer Edward S

    2010-01-01

    Full Text Available Abstract Background Imbalances in the regulation of pro-inflammatory cytokines have been increasingly correlated with a number of severe and prevalent neurodevelopmental disorders, including autism spectrum disorder, schizophrenia and Down syndrome. Although several studies have shown that cytokines have potent effects on neural function, their role in neural development is still poorly understood. In this study, we investigated the link between abnormal cytokine levels and neural development using the Xenopus laevis tadpole visual system, a model frequently used to examine the anatomical and functional development of neural circuits. Results Using a test for a visually guided behavior that requires normal visual system development, we examined the long-term effects of prolonged developmental exposure to three pro-inflammatory cytokines with known neural functions: interleukin (IL-1β, IL-6 and tumor necrosis factor (TNF-α. We found that all cytokines affected the development of normal visually guided behavior. Neuroanatomical imaging of the visual projection showed that none of the cytokines caused any gross abnormalities in the anatomical organization of this projection, suggesting that they may be acting at the level of neuronal microcircuits. We further tested the effects of TNF-α on the electrophysiological properties of the retinotectal circuit and found that long-term developmental exposure to TNF-α resulted in enhanced spontaneous excitatory synaptic transmission in tectal neurons, increased AMPA/NMDA ratios of retinotectal synapses, and a decrease in the number of immature synapses containing only NMDA receptors, consistent with premature maturation and stabilization of these synapses. Local interconnectivity within the tectum also appeared to remain widespread, as shown by increased recurrent polysynaptic activity, and was similar to what is seen in more immature, less refined tectal circuits. TNF-α treatment also enhanced the

  3. Antilipogenic and Anti-Inflammatory Activities of Codonopsis lanceolata in Mice Hepatic Tissues after Chronic Ethanol Feeding

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    Areum Cha

    2012-01-01

    Full Text Available This study evaluated the antilipogenic and anti-inflammatory effects of Codonopsis lanceolata (C. lanceolata root extract in mice with alcohol-induced fatty liver and elucidated its underlying molecular mechanisms. Ethanol was introduced into the liquid diet by mixing it with distilled water at 5% (wt/v, providing 36% of the energy, for nine weeks. Among the three different fractions prepared from the C. lanceolata root, the C. lanceolata methanol extract (CME exhibited the most remarkable attenuation of alcohol-induced fatty liver with respect to various parameters such as hepatic free fatty acid concentration, body weight loss, and hepatic accumulations of triglyceride and cholesterol. The hepatic gene and protein expression levels were analysed via RT-PCR and Western blotting, respectively. CME feeding significantly restored the ethanol-induced downregulation of the adiponectin receptor (adipoR 1 and of adipoR2, along with their downstream molecules. Furthermore, the study data showed that CME feeding dramatically reversed ethanol-induced hepatic upregulation of toll-like receptor- (TLR- mediated signaling cascade molecules. These results indicate that the beneficial effects of CME against alcoholic fatty livers of mice appear to be with adenosine- and adiponectin-mediated regulation of hepatic steatosis and TLR-mediated modulation of hepatic proinflammatory responses.

  4. A rare case of pulmonary toxoplasmosis in a patient with undifferentiated inflammatory arthritis on chronic methotrexate and corticosteroid therapy.

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    Abdulkareem, Abdullateef; D'Souza, Ryan Steven; Patel, Nitin; Donato, Anthony A

    2017-08-23

    Pulmonary toxoplasmosis is a serious pulmonary condition caused by the protozoan Toxoplasma gondii It typically affects immunocompromised patients presenting acutely with cough, fever, myalgias, arthralgias and lymphadenopathy, and chronically with persistent cough and dyspnoea. Because of its protean features, it can mimic many more common lung conditions in the immunocompromised patient, including atypical pneumonia, Pneumocystis pneumonia and interstitial lung disease. In this article, we present the case of a 55-year-old woman who presented to our hospital with persistent dyspnoea and cough, initially suspected to have an arthritis-related interstitial lung disease. She received a final diagnosis of pulmonary toxoplasmosis after lung biopsy demonstrated Toxoplasma cysts, later confirmed by serology. Treatment with trimethoprim-sulfamethoxazole resulted in significant improvement of her respiratory symptoms after 3 months. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  5. Educational interventions to improve quality of life in people with chronic inflammatory skin diseases: systematic reviews of clinical effectiveness and cost-effectiveness.

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    Pickett, Karen; Loveman, Emma; Kalita, Neelam; Frampton, Geoff K; Jones, Jeremy

    2015-10-01

    Inflammatory skin diseases include a broad range of disorders. For some people, these conditions lead to psychological comorbidities and reduced quality of life (QoL). Patient education is recommended in the management of these conditions and may improve QoL. To assess the clinical effectiveness and cost-effectiveness of educational interventions to improve health-related quality of life (HRQoL) in people with chronic inflammatory skin diseases. Twelve electronic bibliographic databases, including The Cochrane Library, MEDLINE and EMBASE, were searched to July 2014. Bibliographies of retrieved papers were searched and an Advisory Group contacted. Systematic reviews were conducted following standard methodologies. Clinical effectiveness studies were included if they were undertaken in people with a chronic inflammatory skin condition. Educational interventions that aimed to, or could, improve HRQoL were eligible. Studies were required to measure HRQoL, and other outcomes such as disease severity were also included. Randomised controlled trials (RCTs) or controlled clinical trials were eligible. For the review of cost-effectiveness, studies were eligible if they were full economic evaluations, cost-consequence or cost analyses. Seven RCTs were included in the review of clinical effectiveness. Two RCTs focused on children with eczema and their carers. Five RCTs were in adults. Of these, two were of people with psoriasis, one was of people with acne and two were of people with a range of conditions. There were few similarities in the interventions (e.g. the delivery mode, the topics covered, the duration of the education), which precluded any quantitative synthesis. Follow-up ranged from 4 weeks to 12 months, samples sizes were generally small and, overall, the study quality was poor. There appeared to be positive effects on HRQoL in participants with psoriasis in one trial, but no difference between groups in another trial in which participants had less severe

  6. Minocycline through attenuation of oxidative stress and inflammatory response reduces the neuropathic pain in a rat model of chronic constriction injury

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    Abolfazl Abbaszadeh

    2018-02-01

    Full Text Available Objective(s: Several lines of evidence showed that minocycline possesses antioxidant and anti-inflammatory properties. This study aimed to demonstrate the effects of minocycline in rats subjected to chronic constriction injury (CCI. Materials and Methods: In this study four groups (n = 6–8 of rats were used as follows: Sham, CCI, CCI + minocycline (MIN 10 mg/Kg (IP and CCI + MIN 30 mg/Kg (IP. On days 3, 7, 14, and 21 post-surgery hot-plate, acetone, and von Frey tests were carried out. Finally, Motor Nerve Conduction Velocity Evaluation (MNCV assessment was performed and spinal cords were harvested in order to measure tissue concentrations of TNF_α, IL-1β, Glutathione peroxidase (GPx, Superoxide dismutase (SOD and Malondialdehyde (MDA. Extent of perineural inflammation and damage around the sciatic nerve was histopathologically evaluated. Results: Our results demonstrated that CCI significantly caused hyperalgesia and allodynia twenty-one days after CCI. MIN attenuated heat hyperalgesia, cold and mechanical allodynia and MNCV in animals. MIN also decreased the levels of TNF_α and IL-1β. Antioxidative enzymes (SOD, MDA, and GPx were restored following MIN treatment. Our findings showed that MIN decreased perineural inflammation around the sciatic nerve. According to the results, the neuropathic pain reduced in the CCI hyperalgesia model using 30 mg/kg of minocycline. Conclusion: It is suggested that antinociceptive effects of minocycline might be mediated through the inhibition of inflammatory response and attenuation of oxidative stress.

  7. Drug utilization of biological drugs in the treatment of chronic Immune-Mediated Inflammatory Diseases (IMIDs: an observational study on Italian patients

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    Paolo Faccendini

    2017-09-01

    Full Text Available Drug utilization of biological drugs in the treatment of chronic Immune-Mediated Inflammatory Diseases (IMIDs: an observational study on Italian patientsObjectives:The aim of this analysis was to provide an estimate of drug utilization indicators (dose escalation and dose tapering related to biologic drugs in the chronic treatment of adult patients with Immune-Mediated Inflammatory Diseases (IMIDs.Methods:We conducted an observational retrospective cohort analysis using the Policlinico di Tor Vergata (PTV database. We considered all biologic drugs dispensed by the PTV hospital pharmacy between January 2010 and December 2015:abatacept, adalimumab, certolizumab, etanercept, golimumab, infliximab (originator and biosimilar, tocilizumab, and ustekinumab were included. Drug dose escalation and dose tapering were calculated and compared with their Defined Daily Dose (DDD.Results:A total of 1803 patients with IMID and biologic drug prescription were analyzed (male: 51.2%. The majority of patients were in the class 36-50 years (n = 612. The median follow-up was 33.8 months (IQR 14.43-56.20. Dermatology was the ward with the largest number of patients (n = 882; 48.9%, followed by rheumatology (n = 619; 34.3% and gastroenterology (n = 302; 16.8%. Dose escalation was observed in 406 patients (22.5%. Infliximab biosimilar (n = 51 was the biological drug with the highest dose escalation rate (86.3%, followed by infliximab originator (n = 28; 60.3% and ustekinumab (37.8%. Etanercept was the biological drug with the lowest dose escalation rate (7.4%, followed by golimumab (12.2% and adalimumab (13.8%. In 677 patients (37.5% a dose tapering was observed. Etanercept showed the highest rate of patients with dose tapering (41.6%, followed by adalimumab (33.6%.Conclusions:The results of this analysis show that dose modification is quite common in PTV clinical practice. Considering the strong focus on the pharmaceutical expenditure and the need of cost containment

  8. Diagnostic algorithm for relapsing acquired demyelinating syndromes in children.

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    Hacohen, Yael; Mankad, Kshitij; Chong, W K; Barkhof, Frederik; Vincent, Angela; Lim, Ming; Wassmer, Evangeline; Ciccarelli, Olga; Hemingway, Cheryl

    2017-07-18

    To establish whether children with relapsing acquired demyelinating syndromes (RDS) and myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) show distinctive clinical and radiologic features and to generate a diagnostic algorithm for the main RDS for clinical use. A panel reviewed the clinical characteristics, MOG-Ab and aquaporin-4 (AQP4) Ab, intrathecal oligoclonal bands, and Epstein-Barr virus serology results of 110 children with RDS. A neuroradiologist blinded to the diagnosis scored the MRI scans. Clinical, radiologic, and serologic tests results were compared. The findings showed that 56.4% of children were diagnosed with multiple sclerosis (MS), 25.4% with neuromyelitis optica spectrum disorder (NMOSD), 12.7% with multiphasic disseminated encephalomyelitis (MDEM), and 5.5% with relapsing optic neuritis (RON). Blinded analysis defined baseline MRI as typical of MS in 93.5% of children with MS. Acute disseminated encephalomyelitis presentation was seen only in the non-MS group. Of NMOSD cases, 30.7% were AQP4-Ab positive. MOG-Ab were found in 83.3% of AQP4-Ab-negative NMOSD, 100% of MDEM, and 33.3% of RON. Children with MOG-Ab were younger, were less likely to present with area postrema syndrome, and had lower disability, longer time to relapse, and more cerebellar peduncle lesions than children with AQP4-Ab NMOSD. A diagnostic algorithm applicable to any episode of CNS demyelination leads to 4 main phenotypes: MS, AQP4-Ab NMOSD, MOG-Ab-associated disease, and antibody-negative RDS. Children with MS and AQP4-Ab NMOSD showed features typical of adult cases. Because MOG-Ab-positive children showed notable and distinctive clinical and MRI features, they were grouped into a unified phenotype (MOG-Ab-associated disease), included in a new diagnostic algorithm. © 2017 American Academy of Neurology.

  9. Anti-inflammatory effects of salmeterol/fluticasone propionate 50/250 mcg combination therapy in Japanese patients with chronic obstructive pulmonary disease

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    Asai K

    2015-04-01

    Full Text Available Kazuhisa Asai,1 Akihiro Kobayashi,2 Yukio Makihara,3 Malcolm Johnson4 1Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, Osaka, Japan; 2Biomedical Data Sciences, 3Medical Affairs Respiratory Department, GlaxoSmithKline, Tokyo, Japan; 4Respiratory Global Franchise, GlaxoSmithKline, Uxbridge, UK Purpose: Using sputum neutrophils as the primary measure, and other inflammation biomarkers, this study evaluated the anti-inflammatory effects of the combination salmeterol 50 mcg and fluticasone propionate 250 mcg (SFC 250 in Japanese patients with chronic obstructive pulmonary disease (COPD. Patients and methods: Patients were treated in a randomized, double-blind, parallel group, placebo-controlled trial with SFC 250 twice daily (n=26 or placebo (n=26 for 12 weeks. At the start and end of treatment, inflammation biomarkers (sputum and serum, lung function, and health status (COPD Assessment Test [CAT] questionnaire were measured. Results: Although a numerical decrease in differential neutrophil count was observed from baseline, SFC 250 did not significantly reduce sputum neutrophils compared with placebo, nor were there significant changes from baseline in the other biomarkers (sputum or serum, lung function, or CAT, versus placebo. Squamous epithelial cell contamination in some sputum samples rendered them unacceptable for analysis, which reduced the sample size to n=19 (SFC 250 and n=10 (placebo. However, inclusion of contaminated samples did not affect the overall trend of the outcome. Ad hoc bootstrap statistical analysis showed a 27.9% (SFC 250 and 1.3% (placebo decrease in sputum neutrophils. Sputum IL-8 decreased by 43.2% after SFC 250 but increased by 48.3% with placebo. Responder analyses showed 42% of patients had ≥20% decrease in neutrophils from baseline; and 47% of patients had a ≥200 pg/mL change in sputum IL-8 following SFC 250 versus 20% after placebo; both changes are considered clinically

  10. Is distal motor and/or sensory demyelination a distinctive feature of anti-MAG neuropathy?

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    Lozeron, Pierre; Ribrag, Vincent; Adams, David; Brisset, Marion; Vignon, Marguerite; Baron, Marine; Malphettes, Marion; Theaudin, Marie; Arnulf, Bertrand; Kubis, Nathalie

    2016-09-01

    To report the frequency of the different patterns of sensory and motor electrophysiological demyelination distribution in patients with anti-MAG neuropathy in comparison with patients with IgM neuropathy without MAG reactivity (IgM-NP). Thirty-five anti-MAG patients at early disease stage (20.1 months) were compared to 23 patients with IgM-NP; 21 CIDP patients and 13 patients with CMT1a neuropathy were used as gold standard neuropathies with multifocal and homogeneous demyelination, respectively. In all groups, standard motor and sensory electrophysiological parameters, terminal latency index and modified F ratio were investigated. Motor electrophysiological demyelination was divided in four profiles: distal, homogeneous, proximal, and proximo-distal. Distal sensory and sensorimotor demyelination were evaluated. Anti-MAG neuropathy is a demyelinating neuropathy in 91 % of cases. In the upper limbs, reduced TLI is more frequent in anti-MAG neuropathy, compared to IgM-NP. But, predominant distal demyelination of the median nerve is encountered in only 43 % of anti-MAG neuropathy and is also common in IgM-NP (35 %). Homogeneous demyelination was the second most frequent pattern (31 %). Concordance of electrophysiological profiles across motor nerves trunks is low and median nerve is the main site of distal motor conduction slowing. Reduced sensory conduction velocities occurs in 14 % of patients without evidence of predominant distal slowing. Simultaneous sensory and motor distal slowing was more common in the median nerve of anti-MAG neuropathy than IgM-NP. Electrophysiological distal motor demyelination and sensory demyelination are not a distinctive feature of anti-MAG reactivity. In anti-MAG neuropathy it is mainly found in the median nerve suggesting a frequent nerve compression at wrist.

  11. Evidence of inflammatory immune signaling in chronic fatigue syndrome: A pilot study of gene expression in peripheral blood

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    Vernon Suzanne D

    2008-09-01

    Full Text Available Abstract Background Genomic profiling of peripheral blood reveals altered immunity in chronic fatigue syndrome (CFS however interpretation remains challenging without immune demographic context. The object of this work is to identify modulation of specific immune functional components and restructuring of co-expression networks characteristic of CFS using the quantitative genomics of peripheral blood. Methods Gene sets were constructed a priori for CD4+ T cells, CD8+ T cells, CD19+ B cells, CD14+ monocytes and CD16+ neutrophils from published data. A group of 111 women were classified using empiric case definition (U.S. Centers for Disease Control and Prevention and unsupervised latent cluster analysis (LCA. Microarray profiles of peripheral blood were analyzed for expression of leukocyte-specific gene sets and characteristic changes in co-expression identified from topological evaluation of linear correlation networks. Results Median expression for a set of 6 genes preferentially up-regulated in CD19+ B cells was significantly lower in CFS (p = 0.01 due mainly to PTPRK and TSPAN3 expression. Although no other gene set was differentially expressed at p Conclusion Dissection of blood microarray profiles points to B cell dysfunction with coordinated immune activation supporting persistent inflammation and antibody-mediated NK cell modulation of T cell activity. This has clinical implications as the CD19+ genes identified could provide robust and biologically meaningful basis for the early detection and unambiguous phenotyping of CFS.

  12. Flow cytometry analysis of inflammatory cells isolated from the sciatic nerve and DRG after chronic constriction injury in mice.

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    Liu, Liping; Yin, Yan; Li, Fei; Malhotra, Charvi; Cheng, Jianguo

    2017-06-01

    Cellular responses to nerve injury play a central role in the pathogenesis of neuropathic pain. However, the analysis of site specific cellular responses to nerve injury and neuropathic pain is limited to immunohistochemistry staining with numerous limitations. We proposed to apply flow cytometry to overcome some of the limitations and developed two protocols for isolation of cells from small specimens of the sciatic nerve and dorsal root ganglion (DRG) in mice. RESULTS AND COMPARASION WITH EXISTING: methods We found that both the non-enzymatic and enzymatic approaches were highly effective in harvesting a sufficient number of cells for flow cytometry analysis in normal and pathological conditions. The total number of cells in the injury site of the sciatic and its DRGs increased significantly 14days after chronic constriction injury (CCI) of the sciatic nerve, compared to sham surgery control or the contralateral control. The enzymatic approach yielded a significantly higher total number of cells and CD45 negative cells, suggesting that this approach allows for harvest of more resident cells, compared to the non-enzymatic method. The percentage of CD45 + /CD11b + cells was significantly increased in the sciatic nerve but not in the DRG. These results were consistent with both protocols. We thus offer two simple and effective protocols that allow for application of flow cytometry to the investigation of cellular and molecular mechanisms of neuropathic pain. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. [The echographic assessment of the activity of the inflammatory process in patients with chronic acalculous cholecystitis in the choleretic test].

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    Ivanov, L A; Barashkov, M N

    1995-01-01

    Ultrasonic investigations of the gallbladder in choleretic test were carried out in 186 patients with chronic acalculous cholecystitis (CAC): 47 with intensive, 76 with moderate and 31 with minimal exacerbation, 32 patients in remission and 36 control subjects. As shown by choleretic test, a reduction of latent period and gallbladder contraction duration, a decrease in discharged bile amount, bile discharge velocity, initial and final gallbladder volumes' ration and increased final gallbladder volume occurred in CAC patients. These changes were parallel to inflammation intensity. Three types of gallbladder contraction were revealed in choleretic test: a 3-phase contraction curve with the initial fast evacuation period, relaxation wave (enlarged gallbladder) and slow evacuation period (type 1); a 2-phase curve with fast and slow evacuation (type 2); a monophasic curve with slow evacuation (type 3). In the patients studied type 1 prevailed, while type 3 was not observed in the controls. With increasing inflammation activity in CAC patients a type-1 contraction frequency declined and disappeared in active exacerbation, whereas type 2 and especially type 3 contractions became more frequent.

  14. Role of T-lymphocytes and pro-inflammatory mediators in the pathogenesis of chronic obstructive pulmonary disease

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    Aneal Gadgil

    2008-11-01

    Full Text Available Aneal Gadgil, Steven R DuncanDivision of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USAAbstract: Chronic obstructive pulmonary disease (COPD is the fourth leading cause of death in the US and a major worldwide healthcare problem. The pathophysiologic mechanisms that drive development and progression of this disease are complex and only poorly understood. While tobacco smoking is the primary risk factor, other disease processes also appear to play a role. Components of the innate immune system (eg, macrophages and neutrophils have long been believed to be important in the development of COPD. More recent evidence also suggests involvement of the adaptive immune system in pathogenesis of this disease. Here we will review the literature supporting the participation of T-cells in the development of COPD, and comment on the potential antigenic stimuli that may account for these responses. We will further explore the prospective contributions of T-cell derived mediators that could contribute to the inflammation, alveolar wall destruction, and small airway fibrosis of advanced COPD. A better understanding of these complex immune processes will lead to new insights that could result in improved preventative and/or treatment strategies.Keywords: COPD, T-lymphocytes, adaptive immunity, cytokines

  15. Curcumin in inflammatory diseases.

    Science.gov (United States)

    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. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.

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

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    Morooka, Nobukatsu, E-mail: amorooka@gunma-u.ac.jp [Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-machi, Maebashi, Gunma, 371-8512 (Japan); Ueguri, Kei [Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-machi, Maebashi, Gunma, 371-8512 (Japan); Yee, Karen Kar Lye [Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-machi, Maebashi, Gunma, 371-8512 (Japan); Human Resources Cultivation Center, Gunma University, 1-5-1 Tenjin-cho, Kiryushi, Gunma, 376-8515 (Japan); Yanase, Toshihiko [Department of Endocrinology and Diabetes Mellitus, School of Medicine, Fukuoka University, Jonan-ku, Fukuoka, 814-0180 (Japan); Sato, Takashi [Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-machi, Maebashi, Gunma, 371-8512 (Japan)

    2016-09-02

    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. - Highlights: • DHT, non-aromatizable androgen suppresses Mcp-1 expression in adipocytes. • Mcp-1 transcription was negatively regulated by DHT-AR action. • DHT-AR selectively regulates Mcp-1 transcription through distinct NF-κB sites.

  17. Protective effect of bioactivity guided fractions of Ziziphus jujuba Mill. root bark against hepatic injury and chronic inflammation via inhibiting inflammatory markers and oxidative stress

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    Raghuram Kandimalla

    2016-09-01

    Full Text Available The tribal communities of North Eastern India rely on herbal medicine to cure various disease conditions. Ziziphus jujuba Mill. (Rhamnaceae is one of such medicinal plants used for curing liver ailments, insomnia, anemia, diarrhea, diabetic complications, cancer and loss of appetite. The present study was aimed to describe the protective ability of Z. jujuba root bark against hepatic injury and chronic inflammation. Bioactivity guided fractionation of Z. jujuba methanol extract (ZJME was performed using different solvents of increasing polarity viz. hexane (ZJHF, chloroform (ZJCF, ethyl acetate (ZJEAF, water (ZJWF and residue (ZJMR. In vitro antioxidant results revealed that both ZJME and ZJWF possess strong antioxidant activity among all the fractions and mother extract tested. Further, ZJME and ZJWF showed significant protection against CCl4 intoxicated HepG2 cell lines by means of increased cell viability and decreased LDH levels compared to control group. ZJME at 200, 400 mg/kg and ZJWF at 50, 100 mg/kg inhibited the lipid peroxidation and significantly restored the liver function markers (AST, ALT, ALP, LDH, SOD and CAT and cytokine levels (TNF-α, Il-1β and Il-10 in CCl4 induced acute liver damage in rats. All the results were comparable with standard drug silymarin which was further confirmed by histopathology analysis of liver. Similarly, inflammation and increase inflammatory cytokines levels of carrageenan induced paw edema in rats have been refurbished to normal levels on par with the standard drug indomethacin. ZJWF demonstrated potent response than ZJME in all the biological tests conducted. The results of the study signify the ability of Z. jujuba root bark as good therapeutic agent for liver toxicity and chronic inflammation.

  18. Evaluation of the inflammatory activity in chronic osteomyelitis. Contribution of the scintigraphy with polyclonal antibodies; Avaliacao de atividade inflamatoria em osteomielite cronica. Contribuicao da cintilografia com anticorpos policlonais

    Energy Technology Data Exchange (ETDEWEB)

    Sapienza, Marcelo Tatit

    1996-07-01

    Active chronic osteomyelitis or complicating osteomyelitis (superimposed on diseases that changes the normal bone structure fractures, post-surgery, prosthesis) can be difficult to diagnose by anatomic radiological imaging modalities, like plain radiograph and CT. These diseases frequently cause also increased bone remodeling, leading to nonspecific uptake of Tc-99m-bone scan agents and gallium-67. New radiopharmaceuticals with greater inflammation/infection avidity and specificity are being developed, including the nonspecific polyclonal immunoglobulin (IgG) labeled with technetium-99. Tc-99m-IgG may be available as a ready to use kit, with no reported side effects, low patient absorbed radiation dose and low cost. The mechanism of IgG uptake at the inflammation site has not been fully elucidated yet. Specific (receptor linking, physico-chemical immunoglobulin properties) and nonspecific mechanisms (enhanced vascular permeability and macromolecular exudate) has been suggested. IgG scintigraphy results are affected by the isotope, labeling procedure adopted and characteristics of the inflammatory focus. Nineteen patients with suspected osteomyelitis (active chronic osteomyelitis or violated bone osteomyelitis) were studied by Tc-99m-IgG scintigraphy (directly labeled polyclonal immunoglobulin, Sandoglobuilina - Sandoz). All patients also underwent standard three-phase bone scintigraphy using methylene diphosphonate (Tc-99m-MDP), gallium-67 scintigraphy and plain radiographs. Infection was found in 8 sites. Sensitivity and specificity for Tc-99m-MDP, gallium-67 and Tc 99m-IgG scintigraphy were, respectively, 88 and 36%, 75 and 73%,88 and 82%. All patients with false positive IgG scintigraphies had previous surgery. Other current scintigraphic procedures used in the diagnosis of osteomyelitis are also reviewed. (author)

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

    International Nuclear Information System (INIS)

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

    2016-01-01

    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. - Highlights: • DHT, non-aromatizable androgen suppresses Mcp-1 expression in adipocytes. • Mcp-1 transcription was negatively regulated by DHT-AR action. • DHT-AR selectively regulates Mcp-1 transcription through distinct NF-κB sites.

  20. Food pyramid for subjects with chronic pain: foods and dietary constituents as anti-inflammatory and antioxidant agents.

    Science.gov (United States)

    Rondanelli, Mariangela; Faliva, Milena Anna; Miccono, Alessandra; Naso, Maurizio; Nichetti, Mara; Riva, Antonella; Guerriero, Fabio; De Gregori, Manuela; Peroni, Gabriella; Perna, Simone

    2018-06-01

    Emerging literature suggests that diet constituents may play a modulatory role in chronic pain (CP) through management of inflammation/oxidative stress, resulting in attenuation of pain. We performed a narrative review to evaluate the existing evidence regarding the optimum diet for the management of CP, and we built a food pyramid on this topic. The present review also describes the activities of various natural compounds contained in foods (i.e. phenolic compounds in extra-virgin olive oil (EVO)) listed on our pyramid, which have comparable effects to drug management therapy. This review included 172 eligible studies. The pyramid shows that carbohydrates with low glycaemic index should be consumed every day (three portions), together with fruits and vegetables (five portions), yogurt (125 ml), red wine (125 ml) and EVO; weekly: legumes and fish (four portions); white meat, eggs and fresh cheese (two portions); red or processed meats (once per week); sweets can be consumed occasionally. The food amounts are estimates based on nutritional and practical considerations. At the top of the pyramid there is a pennant: it means that CP subjects may need a specific customised supplementation (vitamin B12, vitamin D, n-3 fatty acids, fibre). The food pyramid proposal will serve to guide dietary intake with to the intent of alleviating pain in CP patients. Moreover, a targeted diet can also help to solve problems related to the drugs used to combat CP, i.e. constipation. However, this paper would be an early hypothetical proposal due to the limitations of the studies.

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

    Directory of Open Access Journals (Sweden)

    Gui Hua Xu

    2015-10-01

    Full Text Available 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 also elicited similar results. Conclusion: Our study suggests PE might be effective in the treatment of CS-induced COPD by inhibiting inflammation.

  2. Modulation of Interleukin-8 and staphylococcal flora by Avène hydrotherapy in patients suffering from chronic inflammatory dermatoses.

    Science.gov (United States)

    Casas, C; Ribet, V; Alvarez-Georges, S; Sibaud, V; Guerrero, D; Schmitt, A-M; Redoulès, D

    2011-02-01

    A number of studies argue in favour of an important role of microbial colonization, in particular of Staphylococcus aureus, in triggering atopic dermatitis (AD) flare-up and psoriasis, in particular through the superantigenic properties of toxins generated by S. aureus. The aim of this study was to assess the efficacy of a 3-week Avène hydrotherapy on the skin surface of patients suffering from psoriasis or atopic dermatitis. Skin samples were taken from healthy subjects or atopic (n = 18) or psoriatic patients (n = 39) undergoing hydrotherapy at Avène at the beginning (D0) and the end of treatment (D18). The severity of the dermatosis was evaluated according to SCORing Atopic Dermatitis (SCORAD) or Psoriasis Area Severity Index (PASI) scores at D0 and D18. Marker of inflammation interleukin 8 (IL-8), S. aureus colonization (protein A) and enterotoxins were assessed in skin samples using RT-PCR. At D0, significant differences were observed between healthy subjects and atopic or psoriatic patients in all the parameters evaluated (IL-8, protein A). At the end of the hydrotherapy, a significant decrease in SCORAD was associated with a significant reduction of IL-8, S. aureus colonization and enterotoxin D in patients with atopic dermatitis. Similarly, a significant decrease in PASI was associated with a significant reduction of IL-8, S. aureus colonization and enterotoxin N in patients with psoriasis. This study demonstrates the positive effects of Avène hydrotherapy on the skin of patients suffering from chronic dermatosis, with decreased inflammation and reduced colonization by S. aureus. © 2010 The Authors. JEADV © 2010 European Academy of Dermatology and Venereology.

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

    Directory of Open Access Journals (Sweden)

    Lucija Tomljenovic PhD

    2014-03-01

    Full Text Available 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.

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

    Science.gov (United States)

    Chimen, Myriam; McGettrick, Helen M; 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

    2015-05-01

    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 zeta delta (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 that of healthy age-matched donors. In both diseases, tonic inhibition of T cell trafficking across inflamed endothelium is lost. Control of patient T cell trafficking is re-established by treatment with exogenous PEPITEM. Moreover, in animal models of peritonitis, hepatic ischemia-reperfusion injury, Salmonella infection, uveitis and Sjögren's syndrome, PEPITEM reduced T cell recruitment into inflamed tissues.

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

    Directory of Open Access Journals (Sweden)

    Zoe eFonseca-Kelly

    2012-05-01

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

  6. A review of MRI evaluation of demyelination in cuprizone murine model

    Energy Technology Data Exchange (ETDEWEB)

    Krutenkova, E., E-mail: len--k@yandex.ru; Pan, E.; Khodanovich, M., E-mail: khodanovich@mail.tsu.ru [National Research Tomsk State University, Lenina pr., 36, Tomsk (Russian Federation)

    2015-11-17

    The cuprizone mouse model of non-autoimmune demyelination reproduces some phenomena of multiple sclerosis and is appropriate for validation and specification of a new method of non-invasive diagnostics. In the review new data which are collected using the new MRI method are compared with one or more conventional MRI tools. Also the paper reviewed the validation of MRI approaches using histological or immunohistochemical methods. Luxol fast blue histological staining and myelin basic protein immunostaining is widespread. To improve the accuracy of non-invasive conventional MRI, multimodal scanning could be applied. The new quantitative MRI method of fast mapping of the macromolecular proton fraction is a reliable biomarker of myelin in the brain and can be used for research of demyelination in animals. To date, a validation of MPF method on the CPZ mouse model of demyelination is not performed, although this method is probably the best way to evaluate demyelination using MRI.

  7. CT and MRI 'ring sign' may be due to demyelination: diagnostic pitfall.

    LENUS (Irish Health Repository)

    Kamel, M H

    2012-02-03

    We report a case of acute demyelinating encephalomyelitis (ADEM) in which both CT and MRI showed multiple ring-enhancing lesions suggestive of abscesses or brain tumour. This is a relatively rare phenomenon.

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

    Directory of Open Access Journals (Sweden)

    Bade G

    2014-08-01

    Full Text Available Geetanjali Bade,1 Meraj Alam Khan,2 Akhilesh Kumar Srivastava,1 Parul Khare,1 Krishna Kumar Solaiappan,1 Randeep Guleria,3 Nades Palaniyar,2 Anjana Talwar1 1Department of Physiology, All India Institute of Medical Sciences, New Delhi, India; 2Program in Physiology and Experimental Medicine, The Hospital for Sick Children, Department of Laboratory Medicine and Pathobiology, and Institute of Medical Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada; 3Department of Pulmonary Medicine and Sleep Disorders, All India Institute of Medical Sciences, New Delhi, India Abstract: 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 networks analyses were implemented, using a list of cytokines showing differential expression between healthy controls and patients with COPD by Cytoscape and GeneGo Metacore™ softwares (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

  9. A nationwide survey of pediatric acquired demyelinating syndromes in Japan

    Science.gov (United States)

    Yamaguchi, Y.; Kira, R.; Ishizaki, Y.; Sakai, Y.; Sanefuji, M.; Ichiyama, T.; Oka, A.; Kishi, T.; Kimura, S.; Kubota, M.; Takanashi, J.; Takahashi, Y.; Tamai, H.; Natsume, J.; Hamano, S.; Hirabayashi, S.; Maegaki, Y.; Mizuguchi, M.; Minagawa, K.; Yoshikawa, H.; Kira, J.; Kusunoki, S.; Hara, T.

    2016-01-01

    Objective: To investigate the clinical and epidemiologic features of pediatric acquired demyelinating syndromes (ADS) of the CNS in Japan. Methods: We conducted a nationwide survey and collected clinical data on children with ADS aged 15 years or younger, who visited hospitals between 2005 and 2007. Results: Among 977 hospitals enrolled, 723 (74.0%) responded to our inquiries and reported a total of 439 patients as follows: 244 with acute disseminated encephalomyelitis (ADEM), 117 with multiple sclerosis (MS), 14 with neuromyelitis optica (NMO), and 64 with other ADS. We collected and analyzed detailed data from 204 cases, including those with ADEM (66), MS (58), and NMO (10). We observed the following: (1) the estimated annual incidence rate of pediatric ADEM in Japan was 0.40 per 100,000 children (95% confidence interval [CI], 0.34–0.46), with the lowest prevalence in the north; (2) the estimated prevalence rate of MS was 0.69 per 100,000 children (95% CI, 0.58–0.80), with the lowest prevalence in the south; (3) NMO in Japan was rare, with an estimated prevalence of 0.06 per 100,000 children (95% CI, 0.04–0.08); and (4) the sex ratio and mean age at onset varied by ADS type, and (5) male/female ratios correlated with ages at onset in each ADS group. Conclusions: Our results clarify the characteristic clinical features of pediatric ADS in the Japanese population. PMID:27742816

  10. α7 Nicotinic acetylcholine receptor-mediated anti-inflammatory effect in a chronic migraine rat model via the attenuation of glial cell activation

    Directory of Open Access Journals (Sweden)

    Liu Q

    2018-06-01

    Full Text Available Qing Liu,1 Chaoyang Liu,1 Li Jiang,1 Maolin Li,1 Ting Long,1 Wei He,1 Guangcheng Qin,2 Lixue Chen,2 Jiying Zhou1 1Department of Neurology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China; 2Laboratory Research Center, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China Background: Evidence suggests that the activation of α7 nicotinic acetylcholine receptor (α7nAChR can greatly decrease the neuroinflammation response. Neuroinflammation plays a pivotal role in the pathogenesis of chronic migraine (CM. Clinical observations also show that nicotine gum induces analgesic effects in migraine patients. However, whether α7nAChR is involved in CM is unclear.Objective: To investigate the role of α7nAChR in CM and provide a new therapeutic target for CM.Materials and methods: Thirty-six male Sprague–Dawley rats were distributed randomly into control, CM, PNU-282987, and α-bungarotoxin groups (n=9 rats in each group. The CM model was established by the recurrent daily administration of inflammatory soup on the dura over the course of 1 week. The hind paw threshold and facial allodynia were assessed by the von Frey test. The expression levels of α7nAChR, tumor necrosis factor-alpha, and interleukin-1 beta were analyzed by Western blot and real-time fluorescence quantitative polymerase chain reaction. The location of α7nAChR in the hippocampus was quantified by immunofluorescence, as well as the microglial and astrocyte alterations. Changes in the calcitonin gene-related peptide and the phosphorylated JNK protein among different groups were measured by Western blot.Results: We found that the expression of α7nAChR was reduced after repeated inflammatory soup administration. The increased expression of tumor necrosis factor-alpha, interleukin-1 beta, and calcitonin gene-related peptide in CM group were significantly decreased by PNU-282987 and aggravated by α-bungarotoxin. Moreover, PNU-282987

  11. Association of individual non-steroidal anti-inflammatory drugs and chronic kidney disease: a population-based case control study.

    Directory of Open Access Journals (Sweden)

    Ylenia Ingrasciotta

    Full Text Available Non-steroidal anti-inflammatory agents (NSAIDs are known to be associated with renal damage. No clear evidence exists regarding differential risk of chronic kidney disease (CKD, specifically, across various NSAIDs.The aim of this population-based case-control study was to evaluate the association between use of individual NSAIDs and risk of CKD in a general population of Southern Italy.A nested case-control study was carried out using the general practice Arianna database, identifying incident CKD patients as cases and matched controls from 2006 to 2011. The date of first CKD diagnosis was defined as the index date (ID. Conditional logistic regressions were performed to estimate the risk of CKD associated with NSAIDs by class and individual drugs as compared to non-use during different time windows (within one year, six or three months prior to ID, with the latter being defined as current users. Among current users, the effect of cumulative exposure to these drugs was evaluated.Overall, 1,989 CKD cases and 7,906 matched controls were identified. A statistically significant increase in the risk of CKD was found for current users of oxicams (adjusted OR: 1.68; 95% CI: 1.15-2.44 and concerning individual compounds, for ketorolac (adj. OR: 2.54; 95% CI: 1.45-4.44, meloxicam (adj. OR: 1.98; 95% CI: 1.01-3.87 and piroxicam (adj. OR: 1.95; 95% CI: 1.19-3.21.The risk of CKD varies across individual NSAIDs. Increased risk has been found for ketorolac, which may precipitate subclinical CKD through acute renal damage, and long-term exposure to oxicams, especially meloxicam and piroxicam.

  12. A comparison of patients with Q fever fatigue syndrome and patients with chronic fatigue syndrome with a focus on inflammatory markers and possible fatigue perpetuating cognitions and behaviour.

    Science.gov (United States)

    Keijmel, Stephan P; Saxe, Johanna; van der Meer, Jos W M; Nikolaus, Stephanie; Netea, Mihai G; Bleijenberg, Gijs; Bleeker-Rovers, Chantal P; Knoop, Hans

    2015-10-01

    Comparison of Q fever fatigue syndrome (QFS) and chronic fatigue syndrome (CFS) patients, with a focus on markers of inflammation and fatigue-related cognitive-behavioural variables. Data from two independent prospective studies on QFS (n=117) and CFS (n=173), respectively, were pooled and analyzed. QFS patients were less often female, had a higher BMI, and had less often received treatment for depression before the onset of symptoms. After controlling for symptom duration and correcting for differences in diagnostic criteria for QFS and CFS with respect to the level of impairment and the presence of additional symptoms, differences in the proportion of females and BMI remained significant. After correction, QFS patients were also significantly older. In all analyses QFS patients were as fatigued and distressed as CFS patients, but reported less additional symptoms. QFS patients had stronger somatic attributions, and higher levels of physical activity. No differences were found with regard to inflammatory markers and in other fatigue-related cognitive-behavioural variables. The relationship between cognitive-behavioural variables and fatigue, previously established in CFS, could not be confirmed in QFS patients with the exception of the negative relationship between physical activity and fatigue. Differences and similarities between QFS and CFS patients were found. Although the relationship between perpetuating factors and fatigue previously established in CFS could not be confirmed in QFS patients, the considerable overlap in fatigue-related cognitive-behavioural variables and the relationship found between physical activity and fatigue may suggest that behavioural interventions could reduce fatigue severity in QFS patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. 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.

    Science.gov (United States)

    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.

  14. Tramadol plus metamizole combined or not with anti-inflammatory drugs is clinically effective for moderate to severe chronic pain treatment in cancer patients.

    Science.gov (United States)

    Flôr, Patrícia B; Yazbek, Karina V B; Ida, Keila K; Fantoni, Denise T

    2013-05-01

    To test the effectiveness and safety of tramadol plus metamizole combined or not with a non-steroidal anti-inflammatory drug (NSAID) for treating moderate to severe chronic neoplastic pain in dogs, and its impact on quality of life (QL). Prospective, uncontrolled, open-label, clinical study. Sixty nine client-owned dogs with multiple forms of cancer and visual analog scale (VAS) pain score ≥ 40 after receiving NSAIDs for at least 7 days. The MN group received metamizole + NSAID, MNT group received metamizole + NSAID + tramadol and MT group received metamizole + tramadol. Pain was scored by the 0 to 100 mm VAS (0 = no pain, 100 = worst pain) and analgesic therapy was considered effective if 25 mm differences in VAS scores were observed between day 0 and the follow ups. The QL was evaluated according to a 0 to 36 scoring method for dogs (0 = worst, 36 = best) and side effects were recorded. Data were registered at day 0 (baseline) and at the first and second follow ups (7 and 14 days after day 0, respectively). The MN group had less analgesia at day 7 (25%) and day 14 (42%) than MNT (59%, p = 0.0274; 76%, p = 0.0251, respectively) and MT groups (69%, p = 0.0151; 81%, p = 0.0341, respectively). The QL scores were lower in the MN group at the first (score 23) and second follow up (score 26) than in MNT (27, p = 0.0847; 30, p = 0.0002) and MT (28, p = 0.0384; 31, p = 0.0001) groups. Side effects were more commonly observed in the MN group (87%) than in MNT (24%, p pain in dogs with cancer and improved QL. © 2013 The Authors. Veterinary Anaesthesia and Analgesia © 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

  15. Dyslipidemia rather than Type 2 Diabetes Mellitus or Chronic Periodontitis Affects the Systemic Expression of Pro- and Anti-Inflammatory Genes.

    Science.gov (United States)

    Nepomuceno, Rafael; Villela, Bárbara Scoralick; Corbi, Sâmia Cruz Tfaile; Bastos, Alliny De Souza; Dos Santos, Raquel Alves; Takahashi, Catarina Satie; Orrico, Silvana Regina Perez; Scarel-Caminaga, Raquel Mantuaneli

    2017-01-01

    A high percentage of type 2 diabetes mellitus (T2D) patients are also affected by dyslipidemia and chronic periodontitis (CP), but no studies have determined the gene expression in patients that are simultaneously affected by all three diseases. We investigated the systemic expression of immune-related genes in T2D, dyslipidemia, and CP patients. One hundred and fifty patients were separated into five groups containing 30 individuals each: (G1) poorly controlled T2D with dyslipidemia and CP; (G2) well-controlled T2D with dyslipidemia and CP; (G3) normoglycemic individuals with dyslipidemia and CP; (G4) healthy individuals with CP; (G5) systemic and periodontally healthy individuals. Blood analyses of lipid and glycemic profiles were carried out. The expression of genes, including IL10, JAK1, STAT3, SOCS3, IP10, ICAM1, IFNA, IFNG, STAT1, and IRF1, was investigated by RT-qPCR. Patients with dyslipidemia demonstrated statistically higher expression of the IL10 and IFNA genes, while IFNG, IP10, IRF1, JAK1, and STAT3 were lower in comparison with nondyslipidemic patients. Anti-inflammatory genes, such as IL10 , positively correlated with parameters of glucose, lipid, and periodontal profiles, while proinflammatory genes, such as IFNG , were negatively correlated with these parameters. We conclude that dyslipidemia appears to be the primary disease that is associated with gene expression of immune-related genes, while parameters of T2D and CP were correlated with the expression of these important immune genes.

  16. Effect of laser-assisted scaling and root planing on the expression of pro-inflammatory cytokines in the gingival crevicular fluid of patients with chronic periodontitis: A systematic review.

    Science.gov (United States)

    Kellesarian, Sergio Varela; Malignaggi, Vanessa Ros; Majoka, Hasham Abdullah; Al-Kheraif, Abdulaziz A; Kellesarian, Tammy Varela; Romanos, Georgios E; Javed, Fawad

    2017-06-01

    The aim of the present systematic review was to assess the efficacy of laser-assisted (low level laser therapy [LLLT], high intensity laser therapy [HILT], or antimicrobial photodynamic therapy [aPDT]) scaling and root planing (SRP) compared with SRP alone on the expression of inflammatory cytokines in the gingival crevicular (GCF) of patients with chronic periodontitis (CP). In order to address the focused question: "What is the efficacy of SRP with and without laser and/or aPDT on the expression of pro-inflammatory cytokines in the GCF of patients with CP?" an electronic search without time or language restrictions was conducted up to and including February 2017 in indexed databases using various key words. Twenty-two randomized control trials were included in the present systematic review. Nine studies and six studies assessed the efficacy of LLLT and HILT, as adjunct to SRP, respectively. Seven studies assessed the efficacy of aPDT as adjunct to SRP on down-regulating the expression of pro-inflammatory cytokines in the GCF among patients with CP. The outcomes of the studies included based upon the reduction in the levels of pro-inflammatory cytokines were inconsistent. The role of laser-assisted SRP on the expression of pro-inflammatory cytokines in the GCF of patients with CP remains unclear. Further long term and well-designed randomized clinical trials are needed in this regard. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Neuroimmune regulation of inflammatory responses in inflammatory bowel disease

    NARCIS (Netherlands)

    Rijnierse, Anneke

    2006-01-01

    The term inflammatory bowel disease (IBD) is used to describe chronic inflammatory conditions of the gastro-intestinal tract. Patients suffer from abdominal pain, diarrhea, rectal bleeding and a substantial personal burden. The etiology of IBD is gradually being unraveled but remains a complex

  18. Inflammatory lesions of the spinal cord and the nerve roots in magnetic resonance imaging

    International Nuclear Information System (INIS)

    Sartoretti-Schefer, S.; Wichmann, W.; Valavanis, A.

    1996-01-01

    The MRI examinations of 52 patients with proven inflammatory lesions (39 patients) or tumorous/postactinic lesions of the spinal cord (6 patients) and vasuclar malformations of the spinal cord (7 patients) were retrospectively analyzed. All examinations were performed on a 1.5 T MR unit, using bi- or triplanar T1-w pre- and postcontrast as well as T2-w SE sequences. Clinical and radiological examinations allow a subdivision of inflammations of the spinal cord and the nerve roots into (mening-oradiculo) myelitis and meningoradiculo (myelitis). The MRI patterns of these two inflammatory subtypes vary: Meningoradiculitis presents with an enhancement of the nerve roots and the leptomeninges; myelitis itself is characterized by single or multiple, diffuse or multifocal, with or without nodular, patchy or diffusely enhancing intramedullary lessions, with or without thickening of the cord and leptomeningeal inflammation. The immunologically suppressed patient suffers from viral infections (especially herpes simplex, varicella-zoster virus, cytomegalovirus), bacterial infections (tuberculosis), but rarely viral infections, sarcoidosis and demyelinating diseases. Idiopathic myelitis is also common. Secondary ischemic and demyelinating processes result in a complex morphology of inflammatory lesions on MRI, and therefore the whole spectrum of demyelinating, ischemic and inflammatory lesions has to be included in the differential diagnosis. Even tumors may imitate inflammatory myelitis and radiculitis. Most commonly, meningoradiculitis can be separated from myelitis. A reliable diagnosis of a specific inflammatory lesion is difficult and is mostly achieved in patients with multiple sclerosis and in patients with HIV-associated cytomegalovirus infection. (orig.) [de

  19. Chronic psychological stress and high-fat high-fructose diet disrupt metabolic and inflammatory gene networks in the brain, liver, and gut and promote behavioral deficits in mice.

    Science.gov (United States)

    de Sousa Rodrigues, Maria Elizabeth; Bekhbat, Mandakh; Houser, Madelyn C; Chang, Jianjun; Walker, Douglas I; Jones, Dean P; Oller do Nascimento, Claudia M P; Barnum, Christopher J; Tansey, Malú G

    2017-01-01

    The mechanisms underlying the association between chronic psychological stress, development of metabolic syndrome (MetS), and behavioral impairment in obesity are poorly understood. The aim of the present study was to assess the effects of mild chronic psychological stress on metabolic, inflammatory, and behavioral profiles in a mouse model of diet-induced obesity. We hypothesized that (1) high-fat high-fructose diet (HFHF) and psychological stress would synergize to mediate the impact of inflammation on the central nervous system in the presence of behavioral dysfunction, and that (2) HFHF and stress interactions would impact insulin and lipid metabolism. C57Bl/6 male mice underwent a combination of HFHF and two weeks of chronic psychological stress. MetS-related conditions were assessed using untargeted plasma metabolomics, and structural and immune changes in the gut and liver were evaluated. Inflammation was measured in plasma, liver, gut, and brain. Our results show a complex interplay of diet and stress on gut alterations, energetic homeostasis, lipid metabolism, and plasma insulin levels. Psychological stress and HFHF diet promoted changes in intestinal tight junctions proteins and increases in insulin resistance and plasma cholesterol, and impacted the RNA expression of inflammatory factors in the hippocampus. Stress promoted an adaptive anti-inflammatory profile in the hippocampus that was abolished by diet treatment. HFHF increased hippocampal and hepatic Lcn2 mRNA expression as well as LCN2 plasma levels. Behavioral changes were associated with HFHF and stress. Collectively, these results suggest that diet and stress as pervasive factors exacerbate MetS-related conditions through an inflammatory mechanism that ultimately can impact behavior. This rodent model may prove useful for identification of possible biomarkers and therapeutic targets to treat metabolic syndrome and mood disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Poor sleep quality is associated with greater circulating pro-inflammatory cytokines and severity and frequency of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) symptoms in women.

    Science.gov (United States)

    Milrad, Sara F; Hall, Daniel L; Jutagir, Devika R; Lattie, Emily G; Ironson, Gail H; Wohlgemuth, William; Nunez, Maria Vera; Garcia, Lina; Czaja, Sara J; Perdomo, Dolores M; Fletcher, Mary Ann; Klimas, Nancy; Antoni, Michael H

    2017-02-15

    Poor sleep quality has been linked to inflammatory processes and worse disease outcomes in the context of many chronic illnesses, but less is known in conditions such as chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). This study examines the relationships between sleep quality, pro-inflammatory cytokines, and CFS/ME symptoms. Sixty women diagnosed with CFS/ME were assessed using the Pittsburgh Sleep Quality Index (PSQI), Fatigue Symptom Inventory (FSI) and Center for Disease Control and Prevention (CDC)-based CFS/ME symptom questionnaires. Circulating plasma pro-inflammatory cytokine levels were measured by ELISA. Multiple regression analyses examined associations between sleep, cytokines and symptoms, controlling for age, education, and body mass index. Poor sleep quality (PSQI global score) was associated with greater pro-inflammatory cytokine levels: interleukin-1β (IL-1β) (β=0.258, p=0.043), IL-6 (β=0.281, p=0.033), and tumor necrosis factor-alpha (TNF-α) (β=0.263, p=0.044). Worse sleep quality related to greater fatigue severity (β=0.395, p=0.003) and fatigue-related interference with daily activities (β=0.464, p<0.001), and more severe and frequent CDC-defined core CFS/ME symptoms (β=0.499, p<0.001, and β=0.556, p<0.001, respectively). Results underscore the importance of managing sleep-related difficulties in this patient population. Further research is needed to identify the etiology of sleep disruptions in CFS/ME and mechanistic factors linking sleep quality to symptom severity and inflammatory processes. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Demyelinating evidences in CMS rat model of depression: a DTI study at 7 T.

    Science.gov (United States)

    Hemanth Kumar, B S; Mishra, S K; Trivedi, R; Singh, S; Rana, P; Khushu, S

    2014-09-05

    Depression is among the most debilitating diseases worldwide. Long-term exposure to stressors plays a major role in development of human depression. Chronic mild stress (CMS) seems to be a valid animal model for depression. Diffusion tensor imaging (DTI) is capable of inferring microstructural abnormalities of the white matter and has shown to serve as non-invasive marker of specific pathology. We developed a CMS rat model of depression and validated with behavioral experiments. We measured the diffusion indices (mean diffusivity (MD), fractional anisotropy (FA), axial (λ∥) and radial (λ⊥) diffusivity) to investigate the changes in CMS rat brain during depression onset. Diffusion indices have shown to be useful to discriminate myelin damage from axon loss. DTI was performed in both control and CMS rats (n=10, in each group) and maps of FA, MD, λ∥ and λ⊥ diffusivity values were generated using in-house built software. The diffusion indices were calculated by region of interest (ROI) analysis in different brain regions like the frontal cortex, hippocampus, hypothalamus, cingulum, thalamus, caudate putamen, corpus callosum, cerebral peduncle and sensory motor cortex. The results showed signs of demyelination, reflected by increased MD, decreased FA and increased λ⊥. The results also suggest a possible role of edema or inflammation concerning the brain morphology in CMS rats. The overall finding using DTI suggests there might be a major role of loss of myelin sheath, which leads to disrupted connectivity between the limbic area and the prefrontal cortex during the onset of depression. Our findings indicate that interpretation of these indices may provide crucial information about the type and severity of mood disorders. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. Gold nanoparticles administration induces disarray of heart muscle, hemorrhagic, chronic inflammatory cells infiltrated by small lymphocytes, cytoplasmic vacuolization and congested and dilated blood vessels

    Directory of Open Access Journals (Sweden)

    Abdelhalim Mohamed Anwar K

    2011-12-01

    Full Text Available Abstract Background Despite significant research efforts on cancer therapy, diagnostics and imaging, many challenges remain unsolved. There are many unknown details regarding the interaction of nanoparticles (NPs and biological systems. The structure and properties of gold nanoparticles (GNPs make them useful for a wide array of biological applications. However, for the application of GNPs in therapy and drug delivery, knowledge regarding their bioaccumulation and associated local or systemic toxicity is necessary. Information on the biological fate of NPs, including distribution, accumulation, metabolism, and organ specific toxicity is still minimal. Studies specifically dealing with the toxicity of NPs are rare. The aim of the present study was to investigate the effects of intraperitoneal administration of GNPs on histological alterations of the heart tissue of rats in an attempt to identify and understand the toxicity and the potential role of GNPs as a therapeutic and diagnostic tool. Methods A total of 40 healthy male Wistar-Kyoto rats received 50 μl infusions of 10, 20 and 50 nm GNPs for 3 or 7 days. Animals were randomly divided into groups: 6 GNP-treated rats groups and one control group (NG. Groups 1, 2 and 3 received infusions of 50 μl GNPs of size 10 nm (3 or 7 days, 20 nm (3 or 7 days and 50 nm (3 or 7 days, respectively. Results In comparison with the respective control rats, exposure to GNPs doses produced heart muscle disarray with a few scattered chronic inflammatory cells infiltrated by small lymphocytes, foci of hemorrhage with extravasation of red blood cells, some scattered cytoplasmic vacuolization and congested and dilated blood vessels. None of the above alterations were observed in the heart muscle of any member of the control group. Conclusions The alterations induced by intraperitoneal administration of GNPs were size-dependent, with smaller ones inducing greater affects, and were also related to the time exposure to

  3. Sesquiterpene lactone mix patch testing supplemented with dandelion extract in patients with allergic contact dermatitis, atopic dermatitis and non-allergic chronic inflammatory skin diseases.

    Science.gov (United States)

    Jovanović, M; Poljacki, M; Mimica-Dukić, N; Boza, P; Vujanović, Lj; Duran, V; Stojanović, S

    2004-09-01

    We investigated the value of patch testing with dandelion (Compositae) extract in addition to sesquiterpene lactone (SL) mix in selected patients. After we detected a case of contact erythema multiforme after patch testing with dandelion and common chickweed (Caryophyllaceae), additional testing with common chickweed extract was performed. A total of 235 adults with a mean age of 52.3 years were tested. There were 66 men and 169 women: 53 consecutive patients with allergic contact dermatitis (ACD); 43 with atopic dermatitis (AD); 90 non-atopics suffering from non-allergic chronic inflammatory skin diseases; 49 healthy volunteers. All were tested with SL mix 0.1% petrolatum (pet.) and diethyl ether extracts from Taraxacum officinale (dandelion) 0.1 and 3.0% pet. and from Stellaria media (common chickweed) 0.1 and 3% pet. A total of 14 individuals (5.9%) showed allergic reaction (AR) to at least 1 of the plant allergens, 4 (28.6%) to common chickweed extract, and 11 (78.6%) to Compositae allergens. These 11 persons made the overall prevalence of 4.7%: 8 (3.4%) were SL-positive and 3 (1.3%) reacted to dandelion extract. 5 persons (45.5%) had AD, 2 had ACD, 2 had psoriasis and 2 were healthy controls. The Compositae allergy was relevant in 8 cases (72.7%). The highest frequency of SL mix sensitivity (9.3%) was among those with AD. Half the SL mix-sensitive individuals had AD. ARs to dandelion extract were obtained only among patients with eczema. A total of 9 irritant reactions (IRs) in 9 individuals (3.8%) were recorded, 8 to SL mix and 1 to common chickweed extract 3.0% pet. No IR was recorded to dandelion extract (P = 0.007). Among those with relevant Compositae allergy, 50.0% had AR to fragrance mix and balsam of Peru (Myroxylon pereirae resin) and colophonium. SLs were detected in dandelion but not in common chickweed. Our study confirmed the importance of 1 positive reaction for emerging, not fully established, Compositae allergy. In conclusion, the overall

  4. Prescribing patterns of non-steroidal anti-inflammatory drugs in chronic kidney disease patients in the South African private sector.

    Science.gov (United States)

    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

  5. Enhanced accumulation of Kir4.1 protein, but not mRNA, in a murine model of cuprizone-induced demyelination.

    Science.gov (United States)

    Nakajima, Mitsunari; Kawamura, Takuya; Tokui, Ryuji; Furuta, Kohei; Sugino, Mami; Nakanishi, Masayuki; Okuyama, Satoshi; Furukawa, Yoshiko

    2013-11-06

    Two channel proteins, inwardly rectifying potassium channel 4.1 (Kir4.1) and water channel aquaporin-4 (AQP4), were recently identified as targets of an autoantibody response in patients with multiple sclerosis and neuromyelitis optica, respectively. In the present study, we examined the expression patterns of Kir4.1 and AQP4 in a mouse model of demyelination induced by cuprizone, a copper chelator. Demyelination was confirmed by immunohistochemistry using an anti-proteolipid protein antibody in various brain regions, including the corpus callosum, of cuprizone-fed mice. Activation of microglial and astroglial cells was also confirmed by immunohistochemistry, using an anti-ionized calcium binding adapter molecule and a glial fibrillary acidic protein antibody. Western blot analysis revealed the induction of Kir4.1 protein, but not AQP4, in the cortex of cuprizone-fed mice. Immunohistochemical analysis confirmed the Kir4.1 protein induction in microvessels of the cerebral cortex. Real-time polymerase chain reaction analysis revealed that mRNA levels of Kir4.1 and AQP4 in the cortex did not change during cuprizone administration. These findings suggest that enhanced accumulation of Kir4.1 protein in the brain with an inflammatory condition facilitates the autoantibody formation against Kir4.1 in patients with multiple sclerosis. © 2013 Published by Elsevier B.V.

  6. Pain and spinal cord imaging measures in children with demyelinating disease

    Directory of Open Access Journals (Sweden)

    Nadia Barakat

    2015-01-01

    Full Text Available Pain is a significant problem in diseases affecting the spinal cord, including demyelinating disease. To date, studies have examined the reliability of clinical measures for assessing and classifying the severity of spinal cord injury (SCI and also to evaluate SCI-related pain. Most of this research has focused on adult populations and patients with traumatic injuries. Little research exists regarding pediatric spinal cord demyelinating disease. One reason for this is the lack of reliable and useful approaches to measuring spinal cord changes since currently used diagnostic imaging has limited specificity for quantitative measures of demyelination. No single imaging technique demonstrates sufficiently high sensitivity or specificity to myelin, and strong correlation with clinical measures. However, recent advances in diffusion tensor imaging (DTI and magnetization transfer imaging (MTI measures are considered promising in providing increasingly useful and specific information on spinal cord damage. Findings from these quantitative imaging modalities correlate with the extent of demyelination and remyelination. These techniques may be of potential use for defining the evolution of the disease state, how it may affect specific spinal cord pathways, and contribute to the management of pediatric demyelination syndromes. Since pain is a major presenting symptom in patients with transverse myelitis, the disease is an ideal model to evaluate imaging methods to define these regional changes within the spinal cord. In this review we summarize (1 pediatric demyelinating conditions affecting the spinal cord; (2 their distinguishing features; and (3 current diagnostic and classification methods with particular focus on pain pathways. We also focus on concepts that are essential in developing strategies for the detection, monitoring, treatment and repair of pediatric myelitis.

  7. In vitro analysis of the oligodendrocyte lineage in mice during demyelination and remyelination

    International Nuclear Information System (INIS)

    Armstrong, R.; Friedrich, V.L. Jr.; Holmes, K.V.; Dubois-Dalcq, M.

    1990-01-01

    A demyelinating disease induced in C57B1/6N mice by intracranial injection of a coronavirus (murine hepatitis virus strain A59) is followed by functional recovery and efficient CNS myelin repair. To study the biological properties of the cells involved in this repair process, glial cells were isolated and cultured from spinal cords of these young adult mice during demyelination and remyelination. Using three-color immunofluorescence combined with [3H]thymidine autoradiography, we have analyzed the antigenic phenotype and mitotic potential of individual glial cells. We identified oligodendrocytes with an antibody to galactocerebroside, astrocytes with an antibody to glial fibrillary acidic protein, and oligodendrocyte-type 2 astrocyte (O-2A) progenitor cells with the O4 antibody. Cultures from demyelinated tissue differed in several ways from those of age-matched controls: first, the total number of O-2A lineage cells was strikingly increased; second, the O-2A population consisted of a higher proportion of O4-positive astrocytes and cells of mixed oligodendrocyte-astrocyte phenotype; and third, all the cell types within the O-2A lineage showed enhanced proliferation. This proliferation was not further enhanced by adding PDGF, basic fibroblast growth factor (bFGF), or insulin-like growth factor I (IGF-I) to the defined medium. However, bFGF and IGF-I seemed to influence the fate of O-2A lineage cells in cultures of demyelinated tissue. Basic FGF decreased the percentage of cells expressing galactocerebroside. In contrast, IGF-I increased the relative proportion of oligodendrocytes. Thus, O-2A lineage cells from adult mice display greater phenotypic plasticity and enhanced mitotic potential in response to an episode of demyelination. These properties may be linked to the efficient remyelination achieved in this demyelinating disease

  8. Effects of aquatic exercises in a rat model of brainstem demyelination with ethidium bromide on the beam walking test.

    Science.gov (United States)

    Nassar, Cíntia Cristina Souza; Bondan, Eduardo Fernandes; Alouche, Sandra Regina

    2009-09-01

    Multiple sclerosis is a demyelinating disease of the central nervous system associated with varied levels of disability. The impact of early physiotherapeutic interventions in the disease progression is unknown. We used an experimental model of demyelination with the gliotoxic agent ethidium bromide and early aquatic exercises to evaluate the motor performance of the animals. We quantified the number of footsteps and errors during the beam walking test. The demyelinated animals walked fewer steps with a greater number of errors than the control group. The demyelinated animals that performed aquatic exercises presented a better motor performance than those that did not exercise. Therefore aquatic exercising was beneficial to the motor performance of rats in this experimental model of demyelination.

  9. Fluvoxamine stimulates oligodendrogenesis of cultured neural stem cells and attenuates inflammation and demyelination in an animal model of multiple sclerosis.

    Science.gov (United States)

    Ghareghani, Majid; Zibara, Kazem; Sadeghi, Heibatollah; Dokoohaki, Shima; Sadeghi, Hossein; Aryanpour, Roya; Ghanbari, Amir

    2017-07-07

    Multiple Sclerosis (MS) require medications controlling severity of the pathology and depression, affecting more than half of the patients. In this study, the effect of antidepressant drug fluvoxamine, a selective serotonin reuptake inhibitor, was investigated in vitro and in vivo. Nanomolar concentrations of fluvoxamine significantly increased cell viability and proliferation of neural stem cells (NSCs) through increasing mRNA expression of Notch1, Hes1 and Ki-67, and protein levels of NICD. Also, physiological concentrations of fluvoxamine were optimal for NSC differentiation toward oligodendrocytes, astrocytes and neurons. In addition, fluvoxamine attenuated experimental autoimmune encephalomyelitis (EAE) severity, a rat MS model, by significantly decreasing its clinical scores. Moreover, fluvoxamine treated EAE rats showed a decrease in IFN-γ serum levels and an increase in IL-4, pro- and anti-inflammatory cytokines respectively, compared to untreated EAE rats. Furthermore, immune cell infiltration and demyelination plaque significantly decreased in spinal cords of fluvoxamine-treated rats, which was accompanied by an increase in protein expression of MBP and GFAP positive cells and a decrease in lactate serum levels, a new biomarker of MS progression. In summary, besides its antidepressant activity, fluvoxamine stimulates proliferation and differentiation of NSCs particularly toward oligodendrocytes, a producer of CNS myelin.

  10. Targeting demyelination and virtual hypoxia with high-dose biotin as a treatment for progressive multiple sclerosis.

    Science.gov (United States)

    Sedel, Frédéric; Bernard, Delphine; Mock, Donald M; Tourbah, Ayman

    2016-11-01

    Progressive multiple sclerosis (MS) is a severely disabling neurological condition, and an effective treatment is urgently needed. Recently, high-dose biotin has emerged as a promising therapy for affected individuals. Initial clinical data have shown that daily doses of biotin of up to 300 mg can improve objective measures of MS-related disability. In this article, we review the biology of biotin and explore the properties of this ubiquitous coenzyme that may explain the encouraging responses seen in patients with progressive MS. The gradual worsening of neurological disability in patients with progressive MS is caused by progressive axonal loss or damage. The triggers for axonal loss in MS likely include both inflammatory demyelination of the myelin sheath and primary neurodegeneration caused by a state of virtual hypoxia within the neuron. Accordingly, targeting both these pathological processes could be effective in the treatment of progressive MS. Biotin is an essential co-factor for five carboxylases involved in fatty acid synthesis and energy production. We hypothesize that high-dose biotin is exerting a therapeutic effect in patients with progressive MS through two different and complementary mechanisms: by promoting axonal remyelination by enhancing myelin production and by reducing axonal hypoxia through enhanced energy production. This article is part of the Special Issue entitled 'Oligodendrocytes in Health and Disease'. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. Post-chikungunya chronic inflammatory rheumatism: results from a retrospective follow-up study of 283 adult and child cases in La Virginia, Risaralda, Colombia [version 2; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Alfonso J. Rodriguez-Morales

    2016-04-01

    Full Text Available 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.

  12. Lack of effect of chronic pre-treatment with the FAAH inhibitor URB597 on inflammatory pain behaviour: evidence for plastic changes in the endocannabinoid system

    Science.gov (United States)

    Okine, Bright N; Norris, Leonie M; Woodhams, Stephen; Burston, James; Patel, Annie; Alexander, Stephen PH; Barrett, David A; Kendall, David A; Bennett, Andrew J; Chapman, Victoria

    2012-01-01

    BACKGROUND AND PURPOSE Elevating levels of endocannabinoids with inhibitors of fatty acid amide hydrolase (FAAH) is a major focus of pain research, purported to be a safer approach devoid of cannabinoid receptor-mediated side effects. Here, we have determined the effects of sustained pharmacological inhibition of FAAH on inflammatory pain behaviour and if pharmacological inhibition of FAAH was as effective as genetic deletion of FAAH on pain behaviour. EXPERIMENTAL APPROACH Effects of pre-treatment with a single dose, versus 4 day repeated dosing with the selective FAAH inhibitor, URB597 (i.p. 0.3 mg·kg−1), on carrageenan-induced inflammatory pain behaviour and spinal pro-inflammatory gene induction were determined in rats. Effects of pain induction and of the drug treatments on levels of arachidonoyl ethanolamide (AEA), palmitoyl ethanolamide (PEA) and oleolyl ethanolamide (OEA) in the spinal cord were determined. KEY RESULTS Single, but not repeated, URB597 treatment significantly attenuated the development of inflammatory hyperalgesia (P < 0.001, vs. vehicle-treated animals). Neither mode of URB597 treatment altered levels of AEA, PEA and OEA in the hind paw, or carrageenan-induced paw oedema. Single URB597 treatment produced larger increases in AEA, PEA and OEA in the spinal cord, compared with those after repeated administration. Single and repeated URB597 treatment decreased levels of immunoreactive N-acylphosphatidylethanolamine phospholipase D (NAPE-PLD) in the spinal cord and attenuated carrageenan-induced spinal pro-inflammatory gene induction. CONCLUSION AND IMPLICATIONS Changes in the endocannabinoid system may contribute to the loss of analgesic effects following repeated administration of low dose URB597 in this model of inflammatory pain. PMID:22595021

  13. Demyelinating polyneuropathy with focally folded myelin sheaths in a family of Miniature Schnauzer dogs.

    Science.gov (United States)

    Vanhaesebrouck, An E; Couturier, Jérôme; Cauzinille, Laurent; Mizisin, Andrew P; Shelton, G Diane; Granger, Nicolas

    2008-12-15

    A spontaneous demyelinating polyneuropathy in two young Miniature Schnauzer dogs was characterized clinically, electrophysiologically and histopathologically. Both dogs were related and a third dog, belonging to the same family, had similar clinical signs. On presentation, clinical signs were restricted to respiratory dysfunction. Electrophysiological tests showed a dramatic decrease in both motor and sensory nerve conduction velocities. Microscopic examination of peripheral nerve biopsies (light and electron microscopy, teased nerve fibers), showed that this neuropathy was characterized by segmental demyelination and focally folded myelin sheaths. Various clinical syndromes associated with tomacula or focal thickening of the myelin sheath of the peripheral nerves have been described in humans and shown to be caused by gene mutations affecting the myelin proteins, such as the hereditary neuropathy with liability to pressure palsies or the demyelinating forms of Charcot-Marie-Tooth disease. In animals, a tomaculous neuropathy has been reported in cattle and chickens but not in carnivores. Here we report a demyelinating peripheral neuropathy with tomacula in two Miniature Schnauzer dogs.

  14. Bioluminescence Imaging of Olig2-Neural Stem Cells Reveals Improved Engraftment in a Demyelination Mouse Model

    NARCIS (Netherlands)

    Sher, Falak; van Dam, Go; Boddeke, Erik; Copray, Sjef

    2009-01-01

    A major issue in the potential application of neural stem cell (NSC)-based cell replacement therapy for demyelinating diseases is the question of the survival, functional behavior, and stability of implanted NSC-derived oligodendrocyte precursor cells (OPCs) over an extended period. To address this

  15. Lesser-known myelin-related disorders: focal tumour-like demyelinating lesions.

    Science.gov (United States)

    Jiménez Arango, J A; Uribe Uribe, C S; Toro González, G

    2015-03-01

    Focal tumour-like demyelinating lesions are defined as solitary demyelinating lesions with a diameter greater than 2 cm. In imaging studies, these lesions may mimic a neoplasm or brain abscess; as a result, invasive diagnostic and therapeutic measures may be performed that will in some cases increase morbidity. Our aim was to analyse and characterise these lesions according to their clinical, radiological, and pathological characteristics, and this data in addition to our literature review will contribute to a better understanding of these lesions. This descriptive study includes 5 cases with pathological diagnoses. We provide subject characteristics gathered through reviewing their clinical, radiology, and pathology reports. Patients' ages ranged from 12 to 60 years; 3 patients were female. The time delay between symptom onset and hospital admission was 3 to 120 days. Clinical manifestations were diverse and dependent on the location of the lesion, pyramidal signs were found in 80% of patients, there were no clinical or radiological signs of spinal cord involvement, and follow-up times ranged from 1 to 15 years. Brain biopsy is the gold standard for the diagnosis of demyelinating tumour-like lesions; however, their clinical features, along with several magnetic resonance imaging features such as open ring enhancement, venular enhancement, the presence of glutamate in spectroscopy, and others, may be sufficient to differentiate neoplastic lesions from focal tumour-like demyelinating lesions. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  16. Brain white matter demyelinating lesions and amyotrophic lateral sclerosis in a patient with C9orf72 hexanucleotide repeat expansion.

    Science.gov (United States)

    Oliveira Santos, Miguel; Caldeira, Inês; Gromicho, Marta; Pronto-Laborinho, Ana; de Carvalho, Mamede

    2017-10-01

    A hexanucleotide repeat expansion in the C9orf72 gene is associated with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration. It has been described before four patients with multiple sclerosis (MS) and C9orf72-ALS. However, C9orf72 positivity is not associated with increased risk of MS. Inflammatory pathways related to NF-κB have been linked to ALS and MS, and appear to be important in C9orf72-ALS patients. A 42-year-old woman presented with progressive bulbar symptoms for 9 months. Neurological examination disclosed spastic dysarthria, atrophic tongue with fasciculations, brisk jaw and limb tendon reflexes, and bilateral Hoffman sign. Electrophysiological assessment confirmed ALS. Brain MRI revealed multiple and bilateral juxtacortical and periventricular inflammatory changes, some with gadolinium-enhancement, configuring a probable MS-like pattern. CSF evaluation was unremarkable, with no oligoclonal bands. Visual and somatosensory evoked potentials were normal. Follow-up brain MRI 6 months later showed two new lesions in two relatively characteristic locations of MS, with no gadolinium-enhancement. Genetic screening revealed a C9orf72 expansion. As patient had no clinical manifestation of MS, a diagnosis of radiologically isolated syndrome was considered. We speculate that these demyelinating lesions might facilitate expressivity of C9orf72 expansion, through NF-κB activation. This plausible association may lead to the identification of a therapeutic target in this subgroup of C9orf72-ALS patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. 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

    Directory of Open Access Journals (Sweden)

    Emer P. Reeves

    2013-01-01

    Full Text Available 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.

  18. Deep gray matter demyelination detected by magnetization transfer ratio in the cuprizone model.

    Directory of Open Access Journals (Sweden)

    Sveinung Fjær

    Full Text Available In multiple sclerosis (MS, the correlation between lesion load on conventional magnetic resonance imaging (MRI and clinical disability is weak. This clinico-radiological paradox might partly be due to the low sensitivity of conventional MRI to detect gray matter demyelination. Magnetization transfer ratio (MTR has previously been shown to detect white matter demyelination in mice. In this study, we investigated whether MTR can detect gray matter demyelination in cuprizone exposed mice. A total of 54 female C57BL/6 mice were split into one control group ( and eight cuprizone exposed groups ([Formula: see text]. The mice were exposed to [Formula: see text] (w/w cuprizone for up to six weeks. MTR images were obtained at a 7 Tesla Bruker MR-scanner before cuprizone exposure, weekly for six weeks during cuprizone exposure, and once two weeks after termination of cuprizone exposure. Immunohistochemistry staining for myelin (anti-Proteolopid Protein and oligodendrocytes (anti-Neurite Outgrowth Inhibitor Protein A was obtained after each weekly scanning. Rates of MTR change and correlations between MTR values and histological findings were calculated in five brain regions. In the corpus callosum and the deep gray matter a significant rate of MTR value decrease was found, [Formula: see text] per week ([Formula: see text] and [Formula: see text] per week ([Formula: see text] respectively. The MTR values correlated to myelin loss as evaluated by immunohistochemistry (Corpus callosum: [Formula: see text]. Deep gray matter: [Formula: see text], but did not correlate to oligodendrocyte density. Significant results were not found in the cerebellum, the olfactory bulb or the cerebral cortex. This study shows that MTR can be used to detect demyelination in the deep gray matter, which is of pa