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Sample records for inflammatory syndrome tb-iris

  1. Preventing Paradoxical Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome in High-Risk Patients: Protocol of a Randomized Placebo-Controlled Trial of Prednisone (PredART Trial)

    PubMed Central

    Schutz, Charlotte; Blumenthal, Lisette; Thienemann, Friedrich; Buyze, Jozefien; Nöstlinger, Christiana; Ravinetto, Raffaella; Wouters, Edwin; Colebunders, Robert; Maartens, Gary; Wilkinson, Robert J; Lynen, Lutgarde; Meintjes, Graeme

    2016-01-01

    Background Early antiretroviral therapy (ART) initiation in patients diagnosed with HIV-associated tuberculosis (TB) reduces mortality among those with the lowest CD4 counts. At the same time, both early ART and a low CD4 count heighten the risk of paradoxical TB-associated immune reconstitution inflammatory syndrome (TB-IRIS). TB is common in patients starting ART in sub-Saharan Africa. Safe interventions that reduce the incidence or severity of TB-IRIS are needed. Prednisone has been shown to reduce symptoms and markers of inflammation when used to treat TB-IRIS. Objective To determine whether prophylactic prednisone in patients at high risk for paradoxical TB-IRIS initiating ART reduces the incidence of TB-IRIS. Methods We are conducting a randomized, double-blind, placebo-controlled trial of prophylactic prednisone (40 mg/day for 2 weeks, followed by 20 mg/day for 2 weeks) initiated at the same time as ART in patients at high risk for TB-IRIS (starting ART within 30 days of TB treatment and CD4 count ≤100/μL). The primary endpoint is development of TB-IRIS, defined using an international consensus case definition. Secondary endpoints include time to TB-IRIS event, severity of TB-IRIS, quality of life, mortality, hospitalization, other infections and malignancies, and adverse events including corticosteroid adverse effects. Results Enrollment for the trial began in August 2013. All 240 participants have been enrolled, and safety follow-up will be completed in March 2017. Conclusion No preventive strategies for TB-IRIS currently exist. If results of this trial demonstrate the efficacy and safety of prednisone, this will provide clinicians with an evidence-based preventive strategy in patients at high risk for paradoxical TB-IRIS when initiating ART. PMID:27571786

  2. Cytotoxic Mediators in Paradoxical HIV–Tuberculosis Immune Reconstitution Inflammatory Syndrome

    PubMed Central

    Walker, Naomi F.; Meintjes, Graeme; Deffur, Armin; Nicol, Mark P.; Skolimowska, Keira H.; Matthews, Kerryn; Tadokera, Rebecca; Seldon, Ronnett; Maartens, Gary; Rangaka, Molebogeng X.; Besra, Gurdyal S.; Wilkinson, Robert J.

    2015-01-01

    Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) frequently complicates combined antiretroviral therapy and antituberculosis therapy in HIV-1–coinfected tuberculosis patients. The immunopathological mechanisms underlying TB-IRIS are incompletely defined, and improved understanding is required to derive new treatments and to reduce associated morbidity and mortality. We performed longitudinal and cross-sectional analyses of human PBMCs from paradoxical TB-IRIS patients and non-IRIS controls (HIV-TB–coinfected patients commencing antiretroviral therapy who did not develop TB-IRIS). Freshly isolated PBMC stimulated with heat-killed Mycobacterium tuberculosis H37Rv (hkH37Rv) were used for IFN-γ ELISPOT and RNA extraction. Stored RNA was used for microarray and RT-PCR, whereas corresponding stored culture supernatants were used for ELISA. Stored PBMC were used for perforin and granzyme B ELISPOT and flow cytometry. There were significantly increased IFN-γ responses to hkH37Rv in TB-IRIS, compared with non-IRIS PBMC (p = 0.035). Microarray analysis of hkH37Rv-stimulated PBMC indicated that perforin 1 was the most significantly upregulated gene, with granzyme B among the top five (log2 fold difference 3.587 and 2.828, respectively), in TB-IRIS. Downstream experiments using RT-PCR, ELISA, and ELISPOT confirmed the increased expression and secretion of perforin and granzyme B. Moreover, granzyme B secretion reduced in PBMC from TB-IRIS patients during corticosteroid treatment. Invariant NKT cell (CD3+Vα24+) proportions were higher in TB-IRIS patients (p = 0.004) and were a source of perforin. Our data implicate the granule exocytosis pathway in TB-IRIS pathophysiology. Further understanding of the immunopathogenesis of this condition will facilitate development of specific diagnostic and improved therapeutic options. PMID:25589068

  3. Thoracic manifestations of paradoxical immune reconstitution inflammatory syndrome during or after antituberculous therapy in HIV-negative patients.

    PubMed

    Pornsuriyasak, Prapaporn; Suwatanapongched, Thitiporn

    2015-01-01

    Immune reconstitution inflammatory syndrome (IRIS) is a consequence of exaggerated and dysregulated host's inflammatory response to invading microorganism, leading to uncontrolled inflammatory reactions. IRIS associated with tuberculosis (TB) is well recognized among human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy, but it is less common among HIV-negative patients. IRIS can manifest as a paradoxical worsening or recurring of preexisting tuberculous lesions or development of new lesions despite successful antituberculous treatment. Hence, the condition might be misdiagnosed as superimposed infections, treatment failure, or relapse of TB. This pictorial essay reviewed diagnostic criteria and various thoracic manifestations of the paradoxical form of TB-associated IRIS (TB-IRIS) that might aid in early recognition of this clinical entity among HIV-negative patients. The treatment and outcomes of TB-IRIS were also discussed. PMID:25698091

  4. Central Nervous System Immune Reconstitution Inflammatory Syndrome

    PubMed Central

    Boulware, David R.; Marais, Suzaan; Scriven, James; Wilkinson, Robert J.; Meintjes, Graeme

    2013-01-01

    Central nervous system immune reconstitution inflammatory syndrome (CNS-IRIS) develops in 9 %–47 % of persons with HIV infection and a CNS opportunistic infection who start antiretroviral therapy and is associated with a mortality rate of 13 %–75 %. These rates vary according to the causative pathogen. Common CNS-IRIS events occur in relation to Cryptococcus, tuberculosis (TB), and JC virus, but several other mycobacteria, fungi, and viruses have been associated with IRIS. IRIS symptoms often mimic the original infection, and diagnosis necessitates consideration of treatment failure, microbial resistance, and an additional neurological infection. These diagnostic challenges often delay IRIS diagnosis and treatment. Corticosteroids have been used to treat CNS-IRIS, with variable responses; the best supportive evidence exists for the treatment of TB-IRIS. Pathogenic mechanisms vary: Cryptococcal IRIS is characterized by a paucity of cerebrospinal inflammation prior to antiretroviral therapy, whereas higher levels of inflammatory markers at baseline predispose to TB meningitis IRIS. This review focuses on advances in the understanding of CNS-IRIS over the past 2 years. PMID:24173584

  5. Role of LTA4H Polymorphism in Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome Occurrence and Clinical Severity in Patients Infected with HIV

    PubMed Central

    Narendran, Gopalan; Kavitha, Dhanasekaran; Karunaianantham, Ramesh; Gil-Santana, Leonardo; Almeida-Junior, Jilson L.; Reddy, Sirasanambatti Devarajulu; Kumar, Marimuthu Makesh; Hemalatha, Haribabu; Jayanthi, Nagesh Nalini; Ravichandran, Narayanan; Krishnaraja, Raja; Prabhakar, Angamuthu; Manoharan, Tamizhselvan; Nithyananthan, Lokeswaran; Arjunan, Gunasundari; Natrajan, Mohan; Swaminathan, Soumya

    2016-01-01

    Background Paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is an inflammatory phenomenon complicating HIV management in coincidental tuberculosis (TB) infection, upon immune reconstitution driven by antiretroviral therapy (ART). Leukotriene A4 hydroxylase (LTA4H), an enzyme which converts LTA4 to LTB4, regulates the balance between the anti-inflammatory lipoxins and pro-inflammatory LTB4, with direct implications in TB-driven inflammation. In humans, a single nucleotide polymorphism (SNP) in the LTA4H promoter which regulates its transcriptional activity (rs17525495) has been identified and described to impact clinical severity of TB presentation and response to corticosteroid therapy. Notably, the role of LTA4H on TB-IRIS has not been previously evaluated. Here, we performed an exploratory investigation testing the association of LTA4H polymorphism with respect to frequency of TB-IRIS occurrence and severity of TB-IRIS presentation in HIV-TB co-infected individuals. Methods Genotypic evaluation of the LTA4H enzyme from available samples was retrospectively correlated with clinical data captured in case sheets including IRIS details. The cohort included patients recruited from a prospective cohort study nested within a randomized clinical trial (NCT0933790) of ART-naïve HIV+ patients with newly diagnosed rifampicin sensitive pulmonary TB in South India. Frequency of the wild type genotype (CC), as well as of the mutant genotypes (CT or TT) in the IRIS and non-IRIS patients was estimated. Comparative analyses were performed between wild genotype (CC) and the mutant genotypes (CT or TT) and tested for association between the LTA4H polymorphisms and IRIS incidence and clinical severity. Results A total of 142 eligible ART-naïve patients were included in the analyses. Eighty-six individuals exhibited the wild genotype (CC) while 56 had mutant genotypes (43-CT and only 13-TT). Variant allele frequency was 0.23 and 0.26 in non

  6. Natural Killer cell activation distinguishes M. tuberculosis-mediated Immune reconstitution syndrome (IRIS) from chronic HIV and HIV-MTB co-infection

    PubMed Central

    Conradie, F.; Foulkes, A.S.; Ive, P.; Yin, X.; Roussos, K.; Glencross, D.K.; Lawrie, D.; Stevens, W.; Montaner, L.J.; Sanne; Azzoni, L.

    2011-01-01

    Background With increased access to antiretroviral treatment (ART), Immune Reconstitution Inflammatory Syndrome (IRIS) in Mycobacterium tuberculosis (MTB)-infected populations remains a clinical challenge. We studied a cross-sectional cohort of HIV-infected subjects in Johannesburg (South Africa) to help define the immune correlates that best distinguish IRIS from ongoing MTB cases. Methods We studied HIV+ subjects developing MTB-related unmasking IRIS (u-TB-IRIS) after ART initiation; control groups were HIV subjects and HIV-TB co-infected subjects with comparable ART treatment. Testing was conducted with whole blood-based 4-color flow cytometry and plasma-based Luminex cytokine assessment. Results NK cell activation, C-reactive protein and IL-8 serum concentration were significantly higher in u-TB-IRIS subjects as compared to both control groups. In addition, all MTB co-infected subjects, independent of clinical presentation, had higher neutrophils and T cell activation, together with lower lymphocytes, CD4+ T cell and myeloid DC counts. Using conditional inference tree analysis we show that elevated NK cell activation in combination with lymphocyte count characterizes the immunological profile of u-TB-IRIS. Conclusions Our results support a role for innate immune effectors in the immunopathogenesis of unmasking MTB-related IRIS, and identify new immune parameters defining this pathology. PMID:21826013

  7. Vitamin D, d-dimer, Interferon γ, and sCD14 Levels are Independently Associated with Immune Reconstitution Inflammatory Syndrome: A Prospective, International Study☆

    PubMed Central

    Musselwhite, Laura W.; Andrade, Bruno B.; Ellenberg, Susan S.; Tierney, Ann; Belaunzaran-Zamudio, Pablo F.; Rupert, Adam; Lederman, Michael M.; Sanne, Ian; Sierra Madero, Juan G.; Sereti, Irini

    2016-01-01

    To determine the immunological profile most important for IRIS prediction, we evaluated 20 baseline plasma biomarkers in Acquired Immunodeficiency Syndrome (AIDS) patients initiating antiretroviral therapy (ART). Patients were enrolled in a randomized, placebo-controlled ART initiation trial in South Africa and Mexico to test whether maraviroc could prevent IRIS. Participants were classified prospectively as having IRIS within 6 months of ART initiation. Twenty plasma biomarkers were measured at study enrollment for 267 participants. Biomarkers were tested for predicting IRIS with adjustment for covariates chosen through forward stepwise selection. Sixty-two participants developed IRIS and of these 19 were tuberculosis (TB)-IRIS. Baseline levels of vitamin D and higher d-dimer, interferon gamma (IFNγ), and sCD14 were independently associated with risk of IRIS in multivariate analyses. TB-IRIS cases exhibited a distinct biosignature from IRIS related to other pathogens, with increased levels of C-reactive protein (CRP), sCD14, IFNγ, and lower levels of Hb that could be captured by a composite risk score. Elevated markers of Type 1 T helper (Th1) response, monocyte activation, coagulation and low vitamin D were independently associated with IRIS risk. Interventions that decrease immune activation and increase vitamin D levels warrant further study. PMID:26981576

  8. Biomarkers of HIV Immune Reconstitution Inflammatory Syndrome

    PubMed Central

    Bonham, Shuli; Meya, David B; Bohjanen, Paul R; Boulware, David R

    2008-01-01

    Dysregulation of the immune system drives HIV pathogenesis. As we develop new ways to treat HIV and AIDS, we encounter new clinical ramifications of our treatment on regulatory components of the immune system. HIV-associated Immune Reconstitution Inflammatory Syndrome (IRIS) occurs after initiation of anti-retroviral therapy (ART) with inappropriate and dysbalanced restoration of the immune system resulting in pathologic inflammatory reactions with significant morbidity. IRIS is most commonly associated with latent, occult, or past infections, including tuberculosis, Cryptococcus neoformans, and Mycobacterium avium-complex. We discuss common clinical presentations, new diagnostic modalities, current hypotheses of IRIS pathogenesis, and future directions of IRIS-related research, focusing on the identification of biomarkers that can be used to predict and diagnose IRIS. PMID:19057654

  9. Hansen's disease in association with immune reconstitution inflammatory syndrome

    PubMed Central

    George, Anju; Vidyadharan, Suja

    2016-01-01

    Immune reconstitution inflammatory syndrome is characterized by a paradoxical worsening of an existing infection or disease process, soon after initiation of highly active antiretroviral therapy. The first case of leprosy presenting as immune reconstitution inflammatory syndrome was published in 2003. Here we report a case of Hansen's disease borderline tuberculoid presenting with type 1 lepra reaction 5 months after initiation of highly active antiretroviral therapy. PMID:26955584

  10. Hansen's disease in association with immune reconstitution inflammatory syndrome.

    PubMed

    George, Anju; Vidyadharan, Suja

    2016-01-01

    Immune reconstitution inflammatory syndrome is characterized by a paradoxical worsening of an existing infection or disease process, soon after initiation of highly active antiretroviral therapy. The first case of leprosy presenting as immune reconstitution inflammatory syndrome was published in 2003. Here we report a case of Hansen's disease borderline tuberculoid presenting with type 1 lepra reaction 5 months after initiation of highly active antiretroviral therapy. PMID:26955584

  11. Systemic Inflammatory Syndrome Associated with a Case of Jugular Paraganglioma.

    PubMed

    Sokabe, Ayuko; Mizooka, Masafumi; Sakemi, Rinne; Kobayashi, Tomoki; Kishikawa, Nobusuke; Yokobayashi, Kenichi; Kanno, Keishi; Tazuma, Susumu

    2016-01-01

    Jugular paraganlioma is a benign, slow-growing tumor originating from the paraganglion cells and it is associated with catecholamine secretion. Paragangliomas can secrete Interleukin-6 (IL-6) and present as a systemic inflammatory syndrome; these characteristics have not been previously associated with jugular paragangliomas. A 63-year-old man with a jugular tumor in the skull base was referred to our hospital for an evaluation of pyrexia, back pain, and acute inflammation. His serum IL-6 level was elevated on admission and it decreased after radiotherapy. This is the first known case of a jugular paraganglioma exhibiting systemic inflammatory syndrome. PMID:27477424

  12. 'ASIA' - autoimmune/inflammatory syndrome induced by adjuvants.

    PubMed

    Shoenfeld, Yehuda; Agmon-Levin, Nancy

    2011-02-01

    The role of various environmental factors in the pathogenesis of immune mediated diseases is well established. Of which, factors entailing an immune adjuvant activity such as infectious agents, silicone, aluminium salts and others were associated with defined and non-defined immune mediated diseases both in animal models and in humans. In recent years, four conditions: siliconosis, the Gulf war syndrome (GWS), the macrophagic myofasciitis syndrome (MMF) and post-vaccination phenomena were linked with previous exposure to an adjuvant. Furthermore, these four diseases share a similar complex of signs and symptoms which further support a common denominator.Thus, we review herein the current data regarding the role of adjuvants in the pathogenesis of immune mediated diseases as well as the amassed data regarding each of these four conditions. Relating to the current knowledge we would like to suggest to include these comparable conditions under a common syndrome entitled ASIA, "Autoimmune (Auto-inflammatory) Syndrome Induced by Adjuvants". PMID:20708902

  13. Obesity-Driven Gut Microbiota Inflammatory Pathways to Metabolic Syndrome

    PubMed Central

    Cavalcante-Silva, Luiz H. A.; Galvão, José G. F. M.; da Silva, Juliane Santos de França; de Sales-Neto, José M.; Rodrigues-Mascarenhas, Sandra

    2015-01-01

    The intimate interplay between immune system, metabolism, and gut microbiota plays an important role in controlling metabolic homeostasis and possible obesity development. Obesity involves impairment of immune response affecting both innate and adaptive immunity. The main factors involved in the relationship of obesity with inflammation have not been completely elucidated. On the other hand, gut microbiota, via innate immune receptors, has emerged as one of the key factors regulating events triggering acute inflammation associated with obesity and metabolic syndrome. Inflammatory disorders lead to several signaling transduction pathways activation, inflammatory cytokine, chemokine production and cell migration, which in turn cause metabolic dysfunction. Inflamed adipose tissue, with increased macrophages infiltration, is associated with impaired preadipocyte development and differentiation to mature adipose cells, leading to ectopic lipid accumulation and insulin resistance. This review focuses on the relationship between obesity and inflammation, which is essential to understand the pathological mechanisms governing metabolic syndrome. PMID:26635627

  14. Therapeutics targeting inflammation in the immune reconstitution inflammatory syndrome.

    PubMed

    Shahani, Lokesh; Hamill, Richard J

    2016-01-01

    Immune reconstitution inflammatory syndrome (IRIS) is characterized by improvement in a previously incompetent human immune system manifesting as worsening of clinical symptoms secondary to the ability of the immune system to now mount a vigorous inflammatory response. IRIS was first recognized in the setting of human immunodeficiency virus, and this clinical setting continues to be where it is most frequently encountered. Hallmarks of the pathogenesis of IRIS, independent of the clinical presentation and the underlying pathogen, include excessive activation of the immune system, with increased circulating effector memory T cells, and elevated levels of serum cytokines and inflammatory markers. Patients with undiagnosed opportunistic infections remain at risk for unmasking IRIS at the time of active antiretroviral therapy (ART) initiation. Systematic screening for opportunistic infections before starting ART is a key element to prevent this phenomenon. Appropriate management of IRIS requires prompt recognition of the syndrome and exclusion of alternative diagnoses, particularly underlying infections and drug resistance. Controlled studies supporting the use of pharmacologic interventions in IRIS are scare, and recommendations are based on case series and expert opinions. The only controlled trial published to date, showed reduction in morbidity in patients with paradoxical tuberculosis-related IRIS with the use of oral corticosteroids. There are currently limited data to recommend other anti-inflammatory or immunomodulatory therapies that are discussed in this review, and further research is needed. Ongoing research regarding the immune pathogenesis of IRIS will likely direct future rational therapeutic approaches and clinical trials.

  15. Therapeutics targeting inflammation in the immune reconstitution inflammatory syndrome.

    PubMed

    Shahani, Lokesh; Hamill, Richard J

    2016-01-01

    Immune reconstitution inflammatory syndrome (IRIS) is characterized by improvement in a previously incompetent human immune system manifesting as worsening of clinical symptoms secondary to the ability of the immune system to now mount a vigorous inflammatory response. IRIS was first recognized in the setting of human immunodeficiency virus, and this clinical setting continues to be where it is most frequently encountered. Hallmarks of the pathogenesis of IRIS, independent of the clinical presentation and the underlying pathogen, include excessive activation of the immune system, with increased circulating effector memory T cells, and elevated levels of serum cytokines and inflammatory markers. Patients with undiagnosed opportunistic infections remain at risk for unmasking IRIS at the time of active antiretroviral therapy (ART) initiation. Systematic screening for opportunistic infections before starting ART is a key element to prevent this phenomenon. Appropriate management of IRIS requires prompt recognition of the syndrome and exclusion of alternative diagnoses, particularly underlying infections and drug resistance. Controlled studies supporting the use of pharmacologic interventions in IRIS are scare, and recommendations are based on case series and expert opinions. The only controlled trial published to date, showed reduction in morbidity in patients with paradoxical tuberculosis-related IRIS with the use of oral corticosteroids. There are currently limited data to recommend other anti-inflammatory or immunomodulatory therapies that are discussed in this review, and further research is needed. Ongoing research regarding the immune pathogenesis of IRIS will likely direct future rational therapeutic approaches and clinical trials. PMID:26303886

  16. [Non-infectious inflammatory fasciitis: a borderline syndrome].

    PubMed

    Hachulla, E; Janin, A

    1995-01-01

    Inflammatory fasciitis without infection include different entity like eosinophilic fasciitis, the syndrome of eosinophilia-myalgia after tryptophan ingestion, toxic oil syndrome, exposure to trichlorethylene, phenylketonuria skin changes, the syndrome of palmar fasciitis, fasciitis in chronic graft-versus-host disease and fasciitis secondary to an adjacence process. The diagnosis of all these scleroderma-like skin changes is sometimes not easy because the clinical and sometimes the histopathological changes are bordeline manifestations with scleroderma. The most characteristic markers for non infectious fasciitis is eosinophilia and the infiltration of the fascia with eosinophilis, but it may be unremarkable or absent, only frequently present at the onset of the disease. Anamnesis is most important to guide the diagnosis. The eosinophils, but not only, may play a major role in the pathogenesis of this entity.

  17. Susac's syndrome as HIV-associated immune reconstitution inflammatory syndrome.

    PubMed

    Ferretti, Francesca; Gerevini, Simonetta; Colombo, Bruno; Testa, Manuela; Guffanti, Monica; Franciotta, Diego; Bernardi, Gaetano; Lazzarin, Adriano; Cinque, Paola

    2013-09-03

    Susac's Syndrome (SS) is an autoimmune endotheliopathy of cerebral, retinal and cochlear arterioles. We report of an HIV-infected woman who developed a first SS episode following a spontaneous reduction of plasma viral load and several relapses six years later, following initiation of combined antiretroviral therapy (cART). Corticosteroids and intravenous immunoglobulins alone did not control the disease, which improved after combined treatment with acyclovir and ganciclovir. SS onset in HIV infection and relapses during cART-induced immune reconstitution are consistent with the dysimmune nature of the disease. The response to anti-herpes drugs suggests a viral contribute in this case of SS.

  18. Irritable bowel syndrome, inflammatory bowel disease and the microbiome

    PubMed Central

    Major, Giles; Spiller, Robin

    2014-01-01

    Purpose of review The review aims to update the reader on current developments in our understanding of how the gut microbiota impact on inflammatory bowel disease and the irritable bowel syndrome. It will also consider current efforts to modulate the microbiota for therapeutic effect. Recent findings Gene polymorphisms associated with inflammatory bowel disease increasingly suggest that interaction with the microbiota drives pathogenesis. This may be through modulation of the immune response, mucosal permeability or the products of microbial metabolism. Similar findings in irritable bowel syndrome have reinforced the role of gut-specific factors in this ‘functional’ disorder. Metagenomic analysis has identified alterations in pathways and interactions with the ecosystem of the microbiome that may not be recognized by taxonomic description alone, particularly in carbohydrate metabolism. Treatments targeted at the microbial stimulus with antibiotics, probiotics or prebiotics have all progressed in the past year. Studies on the long-term effects of treatment on the microbiome suggest that dietary intervention may be needed for prolonged efficacy. Summary The microbiome represents ‘the other genome’, and to appreciate its role in health and disease will be as challenging as with our own genome. Intestinal diseases occur at the front line of our interaction with the microbiome and their future treatment will be shaped as we unravel our relationship with it. PMID:24296462

  19. Inflammatory biomarkers in asthma-COPD overlap syndrome

    PubMed Central

    Kobayashi, Seiichi; Hanagama, Masakazu; Yamanda, Shinsuke; Ishida, Masatsugu; Yanai, Masaru

    2016-01-01

    Background The clinical phenotypes and underlying mechanisms of asthma-COPD overlap syndrome (ACOS) remain elusive. This study aimed to investigate a comparison of COPD patients with and without ACOS, focusing on inflammatory biomarkers, in an outpatient COPD cohort. Methods We conducted a cross-sectional study analyzing prospectively collected data from the Ishinomaki COPD Network registry. All participants were diagnosed with COPD, confirmed by using spirometry, and were aged 40–90 years and former smokers. Patients with features of asthma including both variable respiratory symptoms and variable expiratory airflow limitation were identified and defined as having ACOS. Then, the inflammatory biomarkers such as fractional exhaled nitric oxide level, blood eosinophil count and percentage, total immunoglobulin E (IgE) level, and presence of antigen-specific IgE were evaluated. Results A total of 257 patients with COPD were identified, including 37 (14.4%) with ACOS. Patients with ACOS tended to be younger, have a shorter smoking history, and use more respiratory medications, especially inhaled corticosteroids and theophylline. Mean fractional exhaled nitric oxide level was significantly higher in those with ACOS than in those without ACOS (38.5 parts per billion [ppb] vs 20.3 ppb, P<0.001). Blood eosinophil count and percentage were significantly increased in those with ACOS (295/mm3 vs 212/mm3, P=0.032; 4.7% vs 3.2%, P=0.003, respectively). Total IgE level was also significantly higher, and presence of antigen-specific IgE was observed more frequently in patients with ACOS. Receiver operating characteristic curve analysis indicated that the sensitivity and specificity of these biomarkers were relatively low, but combinations of these biomarkers showed high specificity for ACOS diagnosis. Conclusion These results provide evidence that these inflammatory biomarkers can be used to support the diagnosis of ACOS.

  20. Inflammatory biomarkers in asthma-COPD overlap syndrome

    PubMed Central

    Kobayashi, Seiichi; Hanagama, Masakazu; Yamanda, Shinsuke; Ishida, Masatsugu; Yanai, Masaru

    2016-01-01

    Background The clinical phenotypes and underlying mechanisms of asthma-COPD overlap syndrome (ACOS) remain elusive. This study aimed to investigate a comparison of COPD patients with and without ACOS, focusing on inflammatory biomarkers, in an outpatient COPD cohort. Methods We conducted a cross-sectional study analyzing prospectively collected data from the Ishinomaki COPD Network registry. All participants were diagnosed with COPD, confirmed by using spirometry, and were aged 40–90 years and former smokers. Patients with features of asthma including both variable respiratory symptoms and variable expiratory airflow limitation were identified and defined as having ACOS. Then, the inflammatory biomarkers such as fractional exhaled nitric oxide level, blood eosinophil count and percentage, total immunoglobulin E (IgE) level, and presence of antigen-specific IgE were evaluated. Results A total of 257 patients with COPD were identified, including 37 (14.4%) with ACOS. Patients with ACOS tended to be younger, have a shorter smoking history, and use more respiratory medications, especially inhaled corticosteroids and theophylline. Mean fractional exhaled nitric oxide level was significantly higher in those with ACOS than in those without ACOS (38.5 parts per billion [ppb] vs 20.3 ppb, P<0.001). Blood eosinophil count and percentage were significantly increased in those with ACOS (295/mm3 vs 212/mm3, P=0.032; 4.7% vs 3.2%, P=0.003, respectively). Total IgE level was also significantly higher, and presence of antigen-specific IgE was observed more frequently in patients with ACOS. Receiver operating characteristic curve analysis indicated that the sensitivity and specificity of these biomarkers were relatively low, but combinations of these biomarkers showed high specificity for ACOS diagnosis. Conclusion These results provide evidence that these inflammatory biomarkers can be used to support the diagnosis of ACOS. PMID:27660429

  1. The spectrum of post-vaccination inflammatory CNS demyelinating syndromes.

    PubMed

    Karussis, Dimitrios; Petrou, Panayiota

    2014-03-01

    A wide variety of inflammatory diseases temporally associated with the administration of various vaccines, has been reported in the literature. A PubMed search from 1979 to 2013 revealed seventy one (71) documented cases. The most commonly reported vaccinations that were associated with CNS demyelinating diseases included influenza (21 cases), human papilloma virus (HPV) (9 cases), hepatitis A or B (8 cases), rabies (5 cases), measles (5 cases), rubella (5 cases), yellow fever (3 cases), anthrax (2 cases),meningococcus (2 cases) and tetanus (2 cases). The vast majority of post-vaccination CNS demyelinating syndromes, are related to influenza vaccination and this could be attributed to the high percentage of the population that received the vaccine during the HI1N1 epidemia from 2009 to 2012. Usually the symptoms of the CNS demyelinating syndrome appear few days following the immunization (mean: 14.2 days) but there are cases where the clinical presentation was delayed (more than 3 weeks or even up to 5 months post-vaccination) (approximately a third of all the reported cases). In terms of the clinical presentation and the affected CNS areas, there is a great diversity among the reported cases of post-vaccination acute demyelinating syndromes. Optic neuritis was the prominent clinical presentation in 38 cases, multifocal disseminated demyelination in 30, myelitis in 24 and encephalitis in 17. Interestingly in a rather high proportion of the patients (and especially following influenza and human papiloma virus vaccination-HPV) the dominant localizations of demyelination were the optic nerves and the myelon, presenting as optic neuritis and myelitis (with or without additional manifestations of ADEM), reminiscent to neuromyelitic optica (or, more generally, the NMO-spectrum of diseases). Seven patients suffered an NMO-like disease following HPV and we had two similar cases in our Center. One patient with post-vaccination ADEM, subsequently developed NMO. Overall, the

  2. Progressive multifocal leukoencephalopathy and immune reconstitution inflammatory syndrome (IRIS).

    PubMed

    Bauer, Jan; Gold, Ralf; Adams, Ortwin; Lassmann, Hans

    2015-12-01

    Progressive multifocal leukoencephalopathy is a viral encephalitis induced by the John Cunningham (JC) virus, an ubiquitous neurotropic papovavirus of the genus polyomavirus that in healthy people in latency resides in kidney and bone marrow cells. Activation and entry into the CNS were first seen in patients with malignancies of the hematopoietic system and an impaired immune system. During the 1980 and the 1990s with the appearance of human immunodeficiency virus infection in humans, PML was found to be the most important opportunistic infection of the central nervous system. As a result of highly efficient immunosuppressive and immunomodulatory treatments, in recent years, the number of PML cases again increased. PML is prevented by an intact cellular immune response and accordingly immune reconstitution can terminate established disease in the CNS. However, forced immune reconstitution can lead to massive destruction of virus-infected cells. This may result in clinical exacerbation associated with high morbidity and mortality and referred to as PML with immune reconstitution inflammatory syndrome (PML-IRIS). In the present review, we discuss virological properties and routes of infection in the CNS, but mostly focus on the pathology of PML and PML-IRIS and on the role of the immune system in these disorders. We show that PML and PML-IRIS result from predominant JC virus infection of oligodendrocytes and, to a lesser extent, of infected neurons. Inflammation in these encephalitides seems to be driven by a dominant cytotoxic T cell response which is massively exaggerated during IRIS. PMID:26323992

  3. Erythema elevatum diutinum in acquired immune deficiency syndrome: Can it be an immune reconstitution inflammatory syndrome?

    PubMed Central

    Jose, Sheethal K; Marfatia, Yogesh S.

    2016-01-01

    A 47-year-old male with acquired immune deficiency syndrome (AIDS) presented with multiple hyperpigmented papules and nodules on both ankles, dorsum of bilateral feet and soles. It was associated with mild itching and pain. The patient was diagnosed with human immunodeficiency virus (HIV) in 2007. First-line antiretroviral therapy (ART) was started in 2009 to which he responded initially. He was shifted to second-line ART 11 months ago in March 2015 due to treatment failure as suggested by CD4 count of 50 cells/mm3. The present skin lesions started 2 months after the initiation of second-line ART. Differential diagnoses considered were Kaposi's sarcoma and immune reconstitution inflammatory syndrome (IRIS) related infections, but biopsy was suggestive of erythema elevatum diutinum (EED). Patient was started on oral dapsone 100 mg/day and increased to 200 mg/day to which he is responding gradually. In the present case, appearance of the lesions after initiation of second-line ART coupled with increase in CD4 count and decrease of viral load below undetectable level suggest that EED could be an IRIS. PMID:27190420

  4. The Biochemical Origin of Pain: The origin of all Pain is Inflammation and the Inflammatory Response. PART 2 of 3 –Inflammatory Profile of Pain Syndromes

    PubMed Central

    2009-01-01

    Every pain syndrome has an inflammatory profile consisting of the inflammatory mediators that are present in the pain syndrome. The inflammatory profile may have variations from one person to another and may have variations in the same person at different times. The key to treatment of Pain Syndromes is an understanding of their inflammatory profile. Pain syndromes may be treated medically or surgically. The goal should be inhibition or suppression of production of the inflammatory mediators and inhibition, suppression or modulation of neuronal afferent and efferent (motor) transmission. A successful outcome is one that results in less inflammation and thus less pain. We hereby describe the inflammatory profile for several pain syndromes including arthritis, back pain, neck pain, fibromyalgia, interstitial cystitis, migraine, neuropathic pain, complex regional pain syndrome / reflex sympathetic dystrophy (CRPS/RSD), bursitis, shoulder pain and vulvodynia. These profiles are derived from basic science and clinical research performed in the past by numerous investigators and will be updated in the future by new technologies such as magnetic resonance spectroscopy. Our unifying theory or law of pain states: The origin of all pain is inflammation and the inflammatory response. The biochemical mediators of inflammation include cytokines, neuropeptides, growth factors and neurotransmitters. Irrespective of the type of pain whether it is acute or chronic pain, peripheral or central pain, nociceptive or neuropathic pain, the underlying origin is inflammation and the inflammatory response. Activation of pain receptors, transmission and modulation of pain signals, neuro plasticity and central sensitization are all one continuum of inflammation and the inflammatory response. Irrespective of the characteristic of the pain, whether it is sharp, dull, aching, burning, stabbing, numbing or tingling, all pain arise from inflammation and the inflammatory response. We are proposing

  5. The biochemical origin of pain: the origin of all pain is inflammation and the inflammatory response. Part 2 of 3 - inflammatory profile of pain syndromes.

    PubMed

    Omoigui, Sota

    2007-01-01

    Every pain syndrome has an inflammatory profile consisting of the inflammatory mediators that are present in the pain syndrome. The inflammatory profile may have variations from one person to another and may have variations in the same person at different times. The key to treatment of Pain Syndromes is an understanding of their inflammatory profile. Pain syndromes may be treated medically or surgically. The goal should be inhibition or suppression of production of the inflammatory mediators and inhibition, suppression or modulation of neuronal afferent and efferent (motor) transmission. A successful outcome is one that results in less inflammation and thus less pain. We hereby briefly describe the inflammatory profile for several pain syndromes including arthritis, back pain, neck pain, fibromyalgia, interstitial cystitis, migraine, neuropathic pain, complex regional pain syndrome/reflex sympathetic dystrophy (CRPS/RSD), bursitis, shoulder pain and vulvodynia. These profiles are derived from basic science and clinical research performed in the past by numerous investigators and serve as a foundation to be built upon by other researchers and will be updated in the future by new technologies such as magnetic resonance spectroscopy. Our unifying theory or law of pain states: the origin of all pain is inflammation and the inflammatory response. The biochemical mediators of inflammation include cytokines, neuropeptides, growth factors and neurotransmitters. Irrespective of the type of pain whether it is acute or chronic pain, peripheral or central pain, nociceptive or neuropathic pain, the underlying origin is inflammation and the inflammatory response. Activation of pain receptors, transmission and modulation of pain signals, neuro plasticity and central sensitization are all one continuum of inflammation and the inflammatory response. Irrespective of the characteristic of the pain, whether it is sharp, dull, aching, burning, stabbing, numbing or tingling, all pain

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

    PubMed

    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.

  7. Acute microbiologically negative hypoxic interstitial pneumonia on HAART: Immune Reconstitution Inflammatory Syndrome unmasking Pneumocystis Jiroveci infection with an atypical presentation

    PubMed Central

    Sovaila, S; de Raigniac, A; Picard, C; Taulera, O; Lascoux-Combe, C; Sereni, D; Bourgarit, A

    2012-01-01

    Highly active antiretroviral therapy for AIDS sometimes engenders inflammatory manifestations resulting from an inappropriate and unbalanced immune-system restoration, called Immune Reconstitution inflammatory Syndrome, which, in turn, can unmask a subclinical infection/pathology. Despite our patient’s evident syndrome, the atypical clinical, microbiologic and radiologic feature of Pneumocystis pneumonia made its diagnosis difficult. PMID:22802889

  8. Pulmonary cryptosporidiosis and immune reconstitution inflammatory syndrome: a case report and review.

    PubMed

    Sullivan, T; Reese, L; Huprikar, S; Lee, M

    2013-04-01

    Cryptosporidium rarely affects the lungs, and is not typically associated with the immune reconstitution inflammatory syndrome (IRIS). We describe the first published case of pulmonary IRIS following the initiation of antiretroviral therapy in a patient with AIDS and pulmonary cryptosporidiosis, and discuss its implications for HIV patient care.

  9. Staphylococcus pseudintermedius infection associated with nodular skin lesions and systemic inflammatory response syndrome in a dog

    PubMed Central

    Min, Sa-Hee; Kang, Min-Hee; Sur, Jung-Hyang; Park, Hee-Myung

    2014-01-01

    A 10-year-old Pekingese dog with atopic dermatitis was referred due to pyrexia, multiple skin nodules, anorexia, and depression. The dog was diagnosed as having systemic inflammatory response syndrome (SIRS) induced by bacterial dermatitis. This case presents diagnosis and treatment of SIRS with staphylococcal skin infection in a dog that was immunosuppressed due to long-term use of corticosteroid. PMID:24790236

  10. Acute Cryptococcal Immune Reconstitution Inflammatory Syndrome in a Patient on Natalizumab

    PubMed Central

    Gundacker, Nathan D.; Jordan, Stephen J.; Jones, Benjamin A.; Drwiega, Joseph C.; Pappas, Peter G.

    2016-01-01

    Presented is the first case of acute immune reconstitution inflammatory syndrome (IRIS)-associated cryptococcal meningoencephalitis in a patient on natalizumab for multiple sclerosis. The patient developed acute cerebral edema after initiation of amphotericin B. We propose several mechanisms that explain the acuity of IRIS in this specific patient population and suggest possible therapies. PMID:27006962

  11. Irritable bowel syndrome and inflammatory bowel disease overlap syndrome: pieces of the puzzle are falling into place

    PubMed Central

    Abdul Rani, Rafiz; Raja Ali, Raja Affendi

    2016-01-01

    Irritable bowel syndrome (IBS), a common gastrointestinal disorder involving the gut-brain axis, and inflammatory bowel disease (IBD), a chronic relapsing inflammatory disorder, are both increasing in incidence and prevalence in Asia. Both have significant overlap in terms of symptoms, pathophysiology, and treatment, suggesting the possibility of IBS and IBD being a single disease entity albeit at opposite ends of the spectrum. We examined the similarities and differences in IBS and IBD, and offer new thoughts and approaches to the disease paradigm. PMID:27799880

  12. A review of the neuro- and systemic inflammatory responses in post concussion symptoms: Introduction of the "post-inflammatory brain syndrome" PIBS.

    PubMed

    Rathbone, Alasdair Timothy Llewelyn; Tharmaradinam, Surejini; Jiang, Shucui; Rathbone, Michel P; Kumbhare, Dinesh A

    2015-05-01

    Post-concussion syndrome is an aggregate of symptoms that commonly present together after head injury. These symptoms, depending on definition, include headaches, dizziness, neuropsychiatric symptoms, and cognitive impairment. However, these symptoms are common, occurring frequently in non-head injured controls, leading some to question the existence of post-concussion syndrome as a unique syndrome. Therefore, some have attempted to explain post-concussion symptoms as post-traumatic stress disorder, as they share many similar symptoms and post-traumatic stress disorder does not require head injury. This explanation falls short as patients with post-concussion syndrome do not necessarily experience many key symptoms of post-traumatic stress disorder. Therefore, other explanations must be sought to explain the prevalence of post-concussion like symptoms in non-head injury patients. Many of the situations in which post-concussion syndrome like symptoms may be experienced such as infection and post-surgery are associated with systemic inflammatory responses, and even neuroinflammation. Post-concussion syndrome itself has a significant neuroinflammatory component. In this review we examine the evidence of neuroinflammation in post-concussion syndrome and the potential role systemic inflammation plays in post-concussion syndrome like symptoms. We conclude that given the overlap between these conditions and the role of inflammation in their etiologies, a new term, post-inflammatory brain syndromes (PIBS), is necessary to describe the common outcomes of many different inflammatory insults. The concept of post-concussion syndrome is in its evolution therefore, the new term post-inflammatory brain syndromes provides a better understanding of etiology of its wide-array of symptoms and the wide array of conditions they can be seen in.

  13. Procalcitonin Biomarker Kinetics to Predict Multiorgan Dysfunction Syndrome in Children With Sepsis and Systemic Inflammatory Response Syndrome

    PubMed Central

    Zurek, Jiri; Vavrina, Martin

    2015-01-01

    Background: Procalcitonin (PCT) kinetics is a good prognosis marker in infectious diseases, but few studies of children sepsis have been performed. Objectives: The aim of our study was to examine kinetics of procalcitonin, to evaluate its relationship with severity and to analyze its usefulness in the prediction of multiorgan dysfunction syndrome (MODS). Patients and Methods: Prospective observational study in an 8-bed pediatric intensive care unit of a university hospital. Sixty-two children aged 0-19 years with systemic inflammatory response syndrome or septic states. The degree of severity was evaluated according pediatric logistic organ dysfunction (PELOD) score. Blood tests to determine levels of PCT were taken if the patients had the criteria of systemic inflammatory response syndrome or sepsis. The serum to determine levels of PCT in control group has been taken from patients undergoing elective surgery. Results: Higher values of PCT were identified in patients with PELOD score 12 and more compared to those with PELOD < 12 (P = 0.016). Similarly, higher PCT values were found in patients who developed MODS in contrast to those without MODS (P = 0.011). According to ROC analysis cut-off value of 4.05 ng/mL was found to best discriminate patients with PELOD < 12 and PELOD ≥ 12 with AUC = 0.675 (P = 0.035). Effect of procalcitonin levels on mortality was not demonstrated. Conclusions: Levels of procalcitonin from day 1 to day 5 are related to the severity and multiorgan dysfunction syndrome in children. PMID:26199699

  14. [The sick building syndrome as a part of 'ASIA' (autoimmune/auto-inflammatory syndrome induced by adjuvants)].

    PubMed

    Maoz-Segal, Ramit; Agmon-Levin, Nancy; Israeli, Eitan; Shoenfeld, Yehuda

    2015-02-01

    The entity 'sick building syndrome' is poorly defined and comprises of a set of symptoms resulting from environmental exposure to a work or a living environment. The symptoms are mainly "allergic"-like and include nasal, eye, and mucous membrane irritation, dry skin as well as respiratory symptoms and general symptoms such as fatigue, lethargy, headaches and fever. The Autoimmune [Auto-inflammatory] Syndrome Induced by Adjuvants (ASIA) is a wider term which describes the role of various environmental factors in the pathogenesis of immune mediated diseases. Factors entailing an immune adjuvant activity such as infectious agents, silicone, aluminium salts and others were found in association with defined and non-defined immune mediated diseases. The sick building syndrome and ASIA share a similar complex of signs and symptoms and probably the same immunological mechanisms which further support a common denominator. PMID:25856869

  15. Ultrasonographic approach to diagnosis of fetal inflammatory response syndrome: a tool for at-risk fetuses?

    PubMed

    Mastrolia, Salvatore Andrea; Erez, Offer; Loverro, Giuseppe; Di Naro, Edoardo; Weintraub, Adi Yehuda; Tirosh, Dan; Baron, Joel; Hershkovitz, Reli

    2016-07-01

    Preterm parturition is a syndrome that may result from many underlying mechanisms. Infection and inflammation are the prominent ones. Intrauterine infection and inflammation have an effect akin to sepsis, and that is similar to systemic inflammatory response in adults. Indeed, there is evidence to support the association of a fetal inflammatory response syndrome (FIRS) to systemic infection and inflammation. The utilization of invasive procedures for the prenatal diagnosis of FIRS is associated with a risk for complications resulting from the invasive method. The progress in the imaging quality of obstetrical ultrasound and the development of novel methods for functional anatomical assessment of the fetal organs may help to identify, noninvasively, fetuses at risk for FIRS in patients presenting with preterm labor. We review the studies describing advanced sonographic modalities and the imaging findings in the heart, thymus, kidney, adrenal glands, and spleen of these fetuses. PMID:26821337

  16. [Target Molecule for a Demyelinating Type of Guillain-Barré Syndrome, Acute Inflammatory Demyelinating Polyneuropathy].

    PubMed

    Mori, Masahiro

    2015-11-01

    Guillain-Barré syndrome is classified into demyelinating type, acute inflammatory demyelinating polyneuropathy (AIDP) and axonal form, acute axonal motor neuropathy (AMAN). It has been clearly established that the target molecule for the former is a ganglioside. In contrast, despite years of effort, the target molecule for the latter has not been identified. Recently, molecules around the nodes of Ranvier have entered the spotlight, and "moesin" was reported to be a target molecule for cytomegalovirus associated-AIDP.

  17. Pathology in euthermic bats with white nose syndrome suggests a natural manifestation of immune reconstitution inflammatory syndrome

    USGS Publications Warehouse

    Meteyer, Carol U.; Barber, Daniel; Mandl, Judith N.

    2012-01-01

    White nose syndrome, caused by Geomyces destructans, has killed more than 5 million cave hibernating bats in eastern North America. During hibernation, the lack of inflammatory cell recruitment at the site of fungal infection and erosion is consistent with a temperature-induced inhibition of immune cell trafficking. This immune suppression allows G. destructans to colonize and erode the skin of wings, ears and muzzle of bat hosts unchecked. Yet, paradoxically, within weeks of emergence from hibernation an intense neutrophilic inflammatory response to G. destructans is generated, causing severe pathology that can contribute to death. We hypothesize that the sudden reversal of immune suppression in bats upon the return to euthermia leads to a form of immune reconstitution inflammatory syndrome (IRIS), which was first described in HIV-infected humans with low helper T lymphocyte counts and bacterial or fungal opportunistic infections. IRIS is a paradoxical and rapid worsening of symptoms in immune compromised humans upon restoration of immunity in the face of an ongoing infectious process. In humans with HIV, the restoration of adaptive immunity following suppression of HIV replication with anti-retroviral therapy (ART) can trigger severe immune-mediated tissue damage that can result in death. We propose that the sudden restoration of immune responses in bats infected with G. destructans results in an IRIS-like dysregulated immune response that causes the post-emergent pathology.

  18. Pathology in euthermic bats with white nose syndrome suggests a natural manifestation of immune reconstitution inflammatory syndrome.

    PubMed

    Meteyer, Carol U; Barber, Daniel; Mandl, Judith N

    2012-11-15

    White nose syndrome, caused by Geomyces destructans, has killed more than 5 million cave hibernating bats in eastern North America. During hibernation, the lack of inflammatory cell recruitment at the site of fungal infection and erosion is consistent with a temperature-induced inhibition of immune cell trafficking. This immune suppression allows G. destructans to colonize and erode the skin of wings, ears and muzzle of bat hosts unchecked. Yet, paradoxically, within weeks of emergence from hibernation an intense neutrophilic inflammatory response to G. destructans is generated, causing severe pathology that can contribute to death. We hypothesize that the sudden reversal of immune suppression in bats upon the return to euthermia leads to a form of immune reconstitution inflammatory syndrome (IRIS). IRIS was first described in HIV-infected humans with low helper T lymphocyte counts and bacterial or fungal opportunistic infections. IRIS is a paradoxical and rapid worsening of symptoms in immune compromised humans upon restoration of immunity in the face of an ongoing infectious process. In humans with HIV, the restoration of adaptive immunity following suppression of HIV replication with anti-retroviral therapy (ART) can trigger severe immune-mediated tissue damage that can result in death. We propose that the sudden restoration of immune responses in bats infected with G. destructans results in an IRIS-like dysregulated immune response that causes the post-emergent pathology. PMID:23154286

  19. Associations among Metabolic Syndrome, Ischemia, Inflammatory, Oxidatives, and Lipids Biomarkers

    PubMed Central

    Valle Gottlieb, Maria Gabriela; da Cruz, Ivana Beatrice Mânica; Duarte, Marta M. F.; Moresco, Rafael Noal; Wiehe, Mário; Schwanke, Carla Helena Augustin; Bodanese, Luiz Carlos

    2010-01-01

    Context: Metabolic syndrome (MS) is described as a cluster of cardiometabolic risk factors. Studies suggest that ischemia-modified albumin (IMA) is a biomarker of cardiovascular diseases. IMA levels could be associated with cardiometabolic risks and represent a possible indication of microvascular dysfunction in MS patients. Objective: To confirm this possible association, we evaluated the association between IMA levels and MS. Design: We performed a case-control study (32 healthy individuals and 74 subjects with MS) to evaluate the association between MS, IMA, and other biomarkers [high-sensitivity C-reactive protein (hs-CRP), oxidized low-density lipoprotein (OxLDL), oxidized low-density lipoprotein autoantibodies (anti-OxLDL), IL-6, lipid profile, and glucose]. Results: The MS group showed higher levels of IMA (0.618 ± 0.1355) as well as higher levels of hs-CRP, OxLDL, anti-OxLDL, and IL-6 than did control subjects (IMA = 0.338 ± 0.0486) (P < 0.01). Multivariate analysis showed that IMA and MS association was independent of sex, age, diabetes mellitus 2, and hypercholesterolemia. Conclusion: We found an association between IMA and MS. Additional studies including prospective genetic variation approaches need to be performed to help elucidate this association between IMA and MS and its potential clinical role. PMID:20016051

  20. Inflammatory pseudotumor of the infratemporal fossa leading to orbital apex syndrome.

    PubMed

    Nishio, Naoki; Fujimoto, Yasushi; Nakashima, Tsutomu

    2014-07-01

    An inflammatory pseudotumor is a rare benign disease presenting with non-specific chronic inflammation, and reported occurrences involving the skull base are relatively rare. A 65-year-old man became aware of pain around the right temporomandibular joint and mild trismus, and palsies of the cranial nerves III, IV, V, and VI were observed. A biopsy was performed under general anesthesia with an infratemporal fossa approach, and he was diagnosed with inflammatory pseudotumor of the infratemporal fossa. There was a rapid improvement in symptoms after the start of steroid administration, and 29 months after the initial consultation, the patient remained under strict observation. The 3 criteria in our department for confirming progression of the disease are (1) clinical symptoms, (2) C-reactive protein levels in blood tests, and (3) contrast effect of the tumor on magnetic resonance imaging. This is a rare case report to demonstrate the inflammatory pseudotumor of the infratemporal fossa leading to orbital apex syndrome.

  1. Plasma levels of inflammatory cytokines in adult Nigerians with the metabolic syndrome

    PubMed Central

    Christiana, Udenze Ifeoma; Casimir, Amadi E.; Nicholas, Awolola Awodele; Christian, Makwe C.; Obiefuna, Ajie I.

    2016-01-01

    Background: The aim of this study is to determine the plasma levels of interleukin 6 (IL-6), tumor necrotic factor alpha (TNF-α, and C-reactive protein (CRP) in adult Nigerians with the metabolic syndrome and to determine the relationship between components of the metabolic syndrome and CRP in adult Nigerians. Subjects and Methods: This was a case–control study of fifty adult men and women with the metabolic syndrome, and fifty age- and sex-matched males and females without the metabolic syndrome. Metabolic syndrome was defined based on the National Cholesterol Education Programme-Adult Treatment Panel III criteria. Written informed consent was obtained from the participants. Blood pressure and anthropometry measurements were taken and venous blood was collected after an overnight fast. The Ethics Committee of the Lagos University Teaching Hospital, Lagos, Nigeria, approved the study protocol. Comparisons of continuous variables and categorical variables were done using the Student's t-test and Chi-square test, respectively. Regression analysis was used to determine the associations between variables. Statistical significance was set at P< 0.05. Results: The age- and sex-matched males and females with and without the metabolic syndrome did not differ in their sociodemographic characteristics. They however differed in some clinical and laboratory parameters such as diastolic blood pressure (P = 0.048), waist circumference (P = 0.002), body mass index (P = 0.012), waist/hip ratio (P = 0.023), high density lipoprotein (HDL) (P = 0.012), and insulin resistance (IR) (P = 0.042). There was a statistically significant increase in the inflammatory marker, CRP (P = 0.019), the cytokines, IL6 (P = 0.040), and TNF-α (P = 0.031) between the subjects with and without metabolic syndrome. There was also a significant association between CRP, waist circumference, IR, and HDL in the metabolic syndrome (P < 0.05). Conclusion: Plasma levels of inflammatory cytokines are raised in

  2. Inflammatory cause of metabolic syndrome via brain stress and NF-κB.

    PubMed

    Cai, Dongsheng; Liu, Tiewen

    2012-02-01

    Metabolic syndrome, a network of medical disorders that greatly increase the risk for developing metabolic and cardiovascular diseases, has reached epidemic levels in many areas of today's world. Despite this alarming medicare situation, scientific understandings on the root mechanisms of metabolic syndrome are still limited, and such insufficient knowledge contributes to the relative lack of effective treatments or preventions for related diseases. Recent interdisciplinary studies from neuroendocrinology and neuroimmunology fields have revealed that overnutrition can trigger intracellular stresses to cause inflammatory changes mediated by molecules that control innate immunity. This type of nutrition-related molecular inflammation in the central nervous system, particularly in the hypothalamus, can form a common pathogenic basis for the induction of various metabolic syndrome components such as obesity, insulin resistance, and hypertension. Proinflammatory NF-κB pathway has been revealed as a key molecular system for pathologic induction of brain inflammation, which translates overnutrition and resulting intracellular stresses into central neuroendocrine and neural dysregulations of energy, glucose, and cardiovascular homeostasis, collectively leading to metabolic syndrome. This article reviews recent research advances in the neural mechanisms of metabolic syndrome and related diseases from the perspective of pathogenic induction by intracellular stresses and NF-κB pathway of the brain. PMID:22328600

  3. Relationship between plasma resistin concentrations, inflammatory chemokines, and components of the metabolic syndrome in adults.

    PubMed

    Aquilante, Christina L; Kosmiski, Lisa A; Knutsen, Shannon D; Zineh, Issam

    2008-04-01

    Recent data suggest that resistin, an adipocyte-derived cytokine, has a putative role in inflammatory processes and metabolic derangements. In vitro data suggest that resistin stimulates the production of inflammatory chemokines, yet the relationship in vivo is largely unknown. The purpose of this study was to determine if a relationship exists between plasma resistin concentrations, plasma inflammatory chemokine aged concentrations (ie, monocyte chemoattractant protein 1 [MCP-1] and epithelial neutrophil activator 78 [ENA-78]), and components of the metabolic syndrome in nondiabetic subjects without known cardiovascular disease (CVD). Plasma samples were obtained from nondiabetic subjects (N = 123) aged 18 to 55 years without known CVD or CVD risk equivalents. The presence of the metabolic syndrome was assessed using consensus guidelines. Fasting plasma resistin, MCP-1, ENA-78, and high-sensitivity C-reactive protein (hs-CRP) concentrations were analyzed. The study population consisted of 67.5% women and 68.3% Caucasians (mean age = 44 +/- 7 years and mean body mass index = 33.3 +/- 6 kg/m(2)). The metabolic syndrome was present in 46.3% of study participants. Resistin concentrations were significantly correlated with white blood cell count (r = 0.326, P < .001), hs-CRP concentrations (r = 0.293, P = .005), MCP-1 concentrations (r = 0.251, P = .005), body mass index (r = 0.193, P = .033), and high-density lipoprotein cholesterol (r = -0.182, P = .044). Resistin concentrations were 1.21 times higher in subjects with the metabolic syndrome compared with those without the metabolic syndrome (P = .003). In stepwise regression analysis, white blood cell count (P < .001) and MCP-1 concentrations (P = .002) were significantly associated with resistin concentrations, independent of hs-CRP, sex, body mass index, presence of the metabolic syndrome, and high-density lipoprotein cholesterol. Data from our cross-sectional study demonstrate that plasma resistin concentrations

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

    PubMed Central

    Ukielska, Bogna; Jończyk-Potoczna, Katarzyna; Konatkowska, Benigna; Wachowiak, Jacek

    2016-01-01

    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. PMID:27800196

  5. Guillain Barre syndrome in an HIV-1-infected patient after the beginning of combined antiretroviral therapy: an immune reconstitution inflammatory syndrome?

    PubMed

    Fantauzzi, Alessandra; Digiulio, Maria Anna; Cavallari, Eugenio Nelson; d'Ettorre, Gabriella; Vullo, Vincenzo; Mezzaroma, Ivano

    2014-01-01

    HIV-1-associated Guillan-Barre syndrome (hGBS) is an ascendant progressive polyradiculoneuropathy described throughout the course of the viral disease, mainly associated with the acute retroviral syndrome. HGBS is occasionally described in severely immunocompromised subjects in the context of the immune reconstitution inflammatory syndrome. The case described occurred soon after the start of a combined antiretroviral treatment in an HIV-1 infected patient with ulcerative colitis in the absence of severe immunosuppression. This manifestation may be interpreted as an uncommon appearance of an immune reconstitution syndrome in the presence of a predisposing autoimmune pathology.

  6. Porcine reproductive and respiratory syndrome virus infection triggers HMGB1 release to promote inflammatory cytokine production

    SciTech Connect

    Duan, Erzhen; Wang, Dang; Luo, Rui; Luo, Jingyi; Gao, Li; Chen, Huanchun; Fang, Liurong Xiao, Shaobo

    2014-11-15

    The high mobility group box 1 (HMGB1) protein is an endogenous damage-associated molecular pattern (DAMP) molecule involved in the pathogenesis of various infectious agents. Based on meta-analysis of all publicly available microarray datasets, HMGB1 has recently been proposed as the most significant immune modulator during the porcine response to porcine reproductive and respiratory syndrome virus (PRRSV) infection. However, the function of HMGB1 in PRRSV pathogenesis is unclear. In this study, we found that PRRSV infection triggers the translocation of HMGB1 from the nucleus to the extracellular milieu in MARC-145 cells and porcine alveolar macrophages. Although HMGB1 has no effect on PRRSV replication, HMGB1 promotes PRRSV-induced NF-κB activation and subsequent expression of inflammatory cytokines through receptors RAGE, TLR2 and TLR4. Our findings show that HMGB1 release, triggered by PRRSV infection, enhances the efficiency of virus-induced inflammatory responses, thereby providing new insights into the pathogenesis of PRRSV infection. - Highlights: • PRRSV infection triggers HMGB1 release from MARC-145 cells and PAMs. • HMGB1 does not significantly affect PRRSV proliferation. • HMGB1 is involved in PRRSV-induced NF-κB activation and inflammatory responses. • HMGB1 promotes PRRSV-induced inflammatory responses through TLR2/4 and RAGE.

  7. Metabolic syndrome, activity of the hypothalamic-pituitary-adrenal axis and inflammatory mediators in depressive disorder.

    PubMed

    Martinac, Marko; Pehar, Davor; Karlović, Dalibor; Babić, Dragan; Marcinko, Darko; Jakovljević, Miro

    2014-03-01

    Depression has been associated with various cardiovascular risk factors such as hypertension, obesity, atherogenic dyslipidemia and hyperglycemia. In depressive disorder, hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis and changes in the immune system have been observed. On the other hand, somatic diseases such as obesity, hyperlipidemia, hypertension and diabetes mellitus type 2 are now perceived as important comorbid conditions in patients with depression. The pathogenesis of the metabolic syndrome and depression is complex and poorly researched; however, it is considered that the interaction of chronic stress, psychotrauma, hypercotisolism and disturbed immune functions contribute to the development of these disorders. The aim of the study was to investigate the relationship between depression and metabolic syndrome regarding the HPA axis dysfunction and altered inflammatory processes. Literature search in Medline and other databases included articles written in English published between 1985 and 2012. Analysis of the literature was conducted using a systematic approach with the search terms such as depression, metabolic syndrome, inflammation, cytokines, glucocorticoids, cortisol, and HPA axis. In conclusion, the relationship between depression and metabolic syndrome is still a subject of controversy. Further prospective studies are required to clarify the possible causal relationship between depression and metabolic syndrome and its components. Furthermore, it is important to explore the possibility of a common biologic mechanism in the pathogenesis of these two disorders, in which special attention should be paid to the immune system function, especially the possible specific mechanisms by which cytokines can induce and maintain depressive symptoms and metabolic disorders. The data presented here emphasize the importance of recognition and treatment of depressive disorders with consequent reduction in the incidence of metabolic syndrome, but

  8. [A case of chronic inflammatory demyelinating polyradiculoneuropathy concomitant with acquired von Willebrand syndrome].

    PubMed

    Ueda, Maki; Kawamura, Nobutoshi; Tateishi, Takahisa; Shigeto, Hiroshi; Ohyagi, Yasumasa; Kira, Jun-ichi

    2011-05-01

    We report a case of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) concomitant with acquired von Willebrand syndrome. A 33-year-old man developed motor and sensory polyneuropathy with electrophysiological conduction slowing. At this time, M-protein was absent He was diagnosed with CIDP and received intravenous immunoglobulin and subsequent oral corticosteroids, which resulted in almost complete remission for over 10 years. At the age of 44, he presented with chronic anemia. Laboratory tests and colonoscopy revealed that he had acquired von Willebrand syndrome with monoclonal gammopathy of undetermined significance (IgG lambda type) and colon cancer. Bleeding symptoms were.resolved with intravenous immunoglobulin, but not with supplementation of factor VIII. Shortly after successful excision of the cancer, CIDP and acquired von Willebrand syndrome simultaneously recurred. Intravenous immunoglobulin produced rapid improvement of both neurological and hematological abnormalities. Concurring CIDP and acquired von Willebrand syndrome in the present case may indicate that the conditions have a partly common immunological background including monoclonal gammopathy and a potential common autoantibody-mediated mechanism. Alternatively, dysfunction of von Willebrand factor may increase blood-nerve barrier permeability, inducing the recurrence of CIDP.

  9. Intravenous Immunoglobulin with Enhanced Polyspecificity Improves Survival in Experimental Sepsis and Aseptic Systemic Inflammatory Response Syndromes

    PubMed Central

    Djoumerska-Alexieva, Iglika; Roumenina, Lubka; Pashov, Anastas; Dimitrov, Jordan; Hadzhieva, Maya; Lindig, Sandro; Voynova, Elisaveta; Dimitrova, Petya; Ivanovska, Nina; Bockmeyer, Clemens; Stefanova, Zvetanka; Fitting, Catherine; Bläss, Markus; Claus, Ralf; von Gunten, Stephan; Kaveri, Srini; Cavaillon, Jean-Marc; Bauer, Michael; Vassilev, Tchavdar

    2015-01-01

    Sepsis is a major cause for death worldwide. Numerous interventional trials with agents neutralizing single proinflammatory mediators have failed to improve survival in sepsis and aseptic systemic inflammatory response syndromes. This failure could be explained by the widespread gene expression dysregulation known as “genomic storm” in these patients. A multifunctional polyspecific therapeutic agent might be needed to thwart the effects of this storm. Licensed pooled intravenous immunoglobulin preparations seemed to be a promising candidate, but they have also failed in their present form to prevent sepsis-related death. We report here the protective effect of a single dose of intravenous immunoglobulin preparations with additionally enhanced polyspecificity in three models of sepsis and aseptic systemic inflammation. The modification of the pooled immunoglobulin G molecules by exposure to ferrous ions resulted in their newly acquired ability to bind some proinflammatory molecules, complement components and endogenous “danger” signals. The improved survival in endotoxemia was associated with serum levels of proinflammatory cytokines, diminished complement consumption and normalization of the coagulation time. We suggest that intravenous immunoglobulin preparations with additionally enhanced polyspecificity have a clinical potential in sepsis and related systemic inflammatory syndromes. PMID:26701312

  10. A severe Whipple disease with an immune reconstitution inflammatory syndrome: an additional case of thalidomide efficiency.

    PubMed

    Le Blay, Pierre; Rakotonirainy, Henintsoa; Lagier, Jean-Christophe; Raoult, Didier; Puechal, Xavier; Pers, Yves-Marie

    2014-05-01

    We report the case of a 38-year-old man who presented with severe diarrhea, weight loss of 10 kg, ankles paresthesia and severe motor weakness in the left fibular nerve territory after introduction of azathioprine and corticosteroid for proteinuria. Coloscopy and gastroscopy revealed a typical aspect of Whipple disease (WD), associated with both positive PAS staining and specific immunohistochemistry. T. whipplei PCR results were positive in blood, faeces, saliva and duodenal biopsy specimens. Diagnosis of WD with systemic manifestations was retained and doxycycline plus hydroxychloroquine therapy were started. This treatment improved joint pain, and skin and intestinal symptoms. One month later, our patient presented with fever and an important inflammatory syndrome (CRP 150 mg/dL and 16.8 10(9)/L leukocytes), while no infection was found despite a thorough review. We concluded it was an immune reconstitution inflammatory syndrome (IRIS). Manifestations persisted despite increasing corticosteroids and thalidomide (200 mg/day) was introduced with good efficacy on these symptoms. WD may be revealed by non-specific symptoms such as weight loss or arthralgia, but also by many other misleading signs. Our observation illustrates the highly polymorphic clinical presentation of WD, and the diagnostic difficulties that may arise. This is also a new report of thalidomide effectiveness in IRIS in WD.

  11. Common links between metabolic syndrome and inflammatory bowel disease: Current overview and future perspectives.

    PubMed

    Michalak, Arkadiusz; Mosińska, Paula; Fichna, Jakub

    2016-08-01

    Metabolic syndrome (MS) features a constellation of central obesity, dyslipidemia, impaired glucose metabolism and often hypertension joined by insulin resistance and chronic inflammation. All these elements greatly raise patient's risk of cardiovascular disease and type 2 diabetes, resulting in an increased mortality. Metabolic syndrome affects approximately 20-25% of the world's adult population and thus it is essential to study its pathophysiology and seek new pharmacological targets. There is a thoroughly studied link between MS and inflammatory diseases of the gastrointestinal (GI) system, i.e. steatohepatitis. However, recent findings also indicate similarities in pathophysiological features between MS and inflammatory bowel disease (IBD), including adipose tissue dysregulation, inadequate immune response, and inflammation. In this review we aim to outline the pathophysiology of MS and emphasize the aspects revealed recently, such as mineralocorticoid activity, involvement of sex hormones and an accompanying increase in prolactin secretion. More importantly, we focus on the common links between MS and IBD. Finally, we describe new strategies and drug targets that may be utilized in MS therapy, namely adiponectin mimetics, GLP-1-based multi agonists, ABCA1 agonists and possible role of miRNA. We also discuss the possible utility of selected agents as adjuvants in IBD therapy.

  12. Susac’s syndrome as HIV-associated immune reconstitution inflammatory syndrome

    PubMed Central

    2013-01-01

    Susac’s Syndrome (SS) is an autoimmune endotheliopathy of cerebral, retinal and cochlear arterioles. We report of an HIV-infected woman who developed a first SS episode following a spontaneous reduction of plasma viral load and several relapses six years later, following initiation of combined antiretroviral therapy (cART). Corticosteroids and intravenous immunoglobulins alone did not control the disease, which improved after combined treatment with acyclovir and ganciclovir. SS onset in HIV infection and relapses during cART-induced immune reconstitution are consistent with the dysimmune nature of the disease. The response to anti-herpes drugs suggests a viral contribute in this case of SS. PMID:24004690

  13. Kefir reduces insulin resistance and inflammatory cytokine expression in an animal model of metabolic syndrome.

    PubMed

    Rosa, Damiana D; Grześkowiak, Łukasz M; Ferreira, Célia L L F; Fonseca, Ana Carolina M; Reis, Sandra A; Dias, Mariana M; Siqueira, Nathane P; Silva, Leticia L; Neves, Clóvis A; Oliveira, Leandro L; Machado, Alessandra B F; Peluzio, Maria do Carmo G

    2016-08-10

    There is growing evidence that kefir can be a promising tool in decreasing the risk of many diseases, including metabolic syndrome (MetS). The aim of the present study was to evaluate the effect of kefir supplementation in the diet of Spontaneously Hypertensive Rats (SHR) in which MetS was induced with monosodium glutamate (MSG), and to determine its effect on metabolic parameters, inflammatory and oxidation marker expression and glycemic index control. Thirty animals were used in this experiment. For the induction of MetS, twenty two-day-old male SHR received five consecutive intradermal injections of MSG. For the Negative Control, ten newborn male SHR received intradermal injections of saline solution (0.9% saline solution). After weaning, animals received standard diet and water ad libitum until reaching 3 months old, for the development of MetS. They were then divided into three groups (n = 10): negative control (NC, 1 mL saline solution per day), positive control (PC, 1 mL saline solution per day) and the Kefir group (1 mL kefir per day). Feeding was carried out by gavage for 10 weeks and the animals received standard food and water ad libitum. Obesity, insulin resistance, pro- and anti-inflammatory markers, and the histology of pancreatic and adipose tissues were among the main variables evaluated. Compared to the PC group, kefir supplementation reduced plasma triglycerides, liver lipids, liver triglycerides, insulin resistance, fasting glucose, fasting insulin, thoracic circumference, abdominal circumference, products of lipid oxidation, pro-inflammatory cytokine expression (IL-1β) and increased anti-inflammatory cytokine expression (IL-10). The present findings indicate that kefir has the potential to benefit the management of MetS. PMID:27384318

  14. Pro- and anti-inflammatory cytokines in human immunodeficiency virus infection and acquired immunodeficiency syndrome.

    PubMed

    Breen, Elizabeth Crabb

    2002-09-01

    In persons with human immunodeficiency virus (HIV) infection and/or acquired immunodeficiency syndrome (AIDS), the immune system becomes dysfunctional in many ways. There is both immunodeficiency due to the loss of CD4-positive T helper cells and hyperactivity as a result of B-cell activation. Likewise, both decreases and increases are seen in the production and/or activity of cytokines. Cytokine changes in HIV infection have been assessed by a variety of techniques, ranging from determination of cytokine gene expression at the mRNA level to secretion of cytokine proteins in vivo and in vitro. Changes in cytokine levels in HIV-infected persons can affect the function of the immune system, and have the potential to directly impact the course of HIV disease by enhancing or suppressing HIV replication. In particular, the balance between the pro-inflammatory cytokines interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha, which up-regulate HIV expression, and IL-10, which can act both as an anti-inflammatory cytokine and a B-cell stimulatory factor, may play an important role in the progression to AIDS. In light of its ability to suppress the production of pro-inflammatory cytokines and, under some conditions, suppress HIV replication, increased IL-10 may be viewed as beneficial in slowing HIV disease progression. However, an association between increased IL-10 and the development of AIDS-associated B-cell lymphoma highlights the bifunctional nature of IL-10 as both an anti-inflammatory and B-cell-stimulatory cytokine that could have beneficial and detrimental effects on the course of HIV infection and AIDS.

  15. Penicillium marneffei presenting as an immune reconstitution inflammatory syndrome (IRIS) in a patient with advanced HIV

    PubMed Central

    Hall, Charlotte; Hajjawi, Rachel; Barlow, Gavin; Thaker, Hiten; Adams, Kate; Moss, Peter

    2013-01-01

    A 62-year-old British man with advanced HIV was established on antiretroviral therapy and treatment for disseminated Mycobacterium avium complex and Cytomegalovirus infections. One month later he re-presented with epigastric pain, an epigastric mass and skin lesions. Abdominal imaging revealed large volume lymphadenopathy, which was not present on previous imaging. Blood cultures yielded Penicillium marneffei, a dimorphic fungus endemic to South-east Asia. The patient had spent several years travelling in Thailand prior to the diagnosis of HIV. Penicilliosis is a common AIDS-defining illness in endemic areas, but remains rare in Europe. In this case, it presented in the context of a rapidly decreasing viral load as an immune reconstitution inflammatory syndrome. The challenges of management in the context of multiple comorbidities and polypharmacy are discussed. PMID:23362074

  16. Challenges in diagnosis and management of Cryptococcal immune reconstitution inflammatory syndrome (IRIS) in resource limited settings.

    PubMed

    Musubire, A K; Meya, B D; Mayanja-Kizza, H; Lukande, R; Wiesner, L D; Bohjanen, P; R Boulware, R D

    2012-06-01

    In many resource-limited settings, cryptococcal meningitis (CM) contributes up to 20% of all deaths with further complications due to Immune Reconstitution Inflammatory Syndrome (IRIS). We present a case report on a patient who developed CM-IRIS and then subsequent CM-relapse with a fluconazole-resistant organism and then later CM-IRIS once again, manifesting as cystic cryptococcomas, hydrocephalus, and sterile CSF. In this case we, demonstrate that CM-IRIS and persistent low level cryptococcal infection are not mutually exclusive phenomena. The management of IRIS with corticosteroids may increase the risk of culture positive CM-relapse which may further increase the risk of recurrent IRIS and resulting complications including death. We also highlight the role of imaging and fluconazole resistance testing in patients with recurrent meningitis and the importance of CSF cultures in guiding treatment decisions.

  17. The Mediterranean diet adoption improves metabolic, oxidative, and inflammatory abnormalities in Algerian metabolic syndrome patients.

    PubMed

    Bekkouche, L; Bouchenak, M; Malaisse, W J; Yahia, D Ait

    2014-04-01

    This study was aimed to explore the effects of Mediterranean diet (MD) adoption on insulin resistance, oxidative, and inflammatory status in metabolic syndrome (MS) patients. Eighty four patients with MS were randomly recruited in the medical centers of Oran, Algeria. Eighteen healthy participants were selected as a control group. Among these 84 patients, only 36 patients completed the nutritional advices for 3 months. Patients were instructed to follow a Mediterranean-style diet and received some other selected nutritional and physical activity instructions. Anthropometric measurements were performed and a questionnaire was used to assess dietary intake. Blood samples were drawn at baseline and after 3 months of nutritional intervention from all subjects. At baseline, the MS patients were obese and had altered anthropometric parameters, higher systolic and diastolic blood pressure, plasma lipids, glucose, insulin, HOMA-IR, HbA1c, urea, creatinine, uric acid, and lower albumin compared to healthy subjects. A decrease in plasma, erythrocyte, and platelet antioxidant enzymes, and a rise in lipid and protein oxidation, plasma CRP, and fibrinogen were noted in the MS patients. Moreover, they had an unbalanced dietary pattern when compared to Mediterranean recommendations. Patients following the Mediterranean-style diet had significantly reduced weight, BMI, waist circumference, waist/hip circumference ratio, decreased systolic and diastolic blood pressure, plasma glucose, insulin, HOMA-IR, HbA1c, cholesterol, triacylglycerols, CRP, urea, creatinine, creatinine clearance, lipid and protein oxidation, and higher plasma, erythrocyte, and platelet antioxidant enzymes. In conclusion, a lifestyle intervention based mainly on nutritional advices improves metabolic, oxidative, and inflammatory abnormalities of metabolic syndrome.

  18. Surgical management of malignant cerebral edema secondary to immune reconstitution inflammatory syndrome from natalizumab-associated progressive multifocal encephalopathy.

    PubMed

    Tan, Lee A; Lopes, Demetrius K

    2015-10-01

    We report a rare multiple sclerosis (MS) patient who developed malignant cerebral edema related to progressive multifocal encephalopathy (PML) immune reconstitution inflammatory syndrome (IRIS) after natalizumab discontinuation. The patient subsequently required a decompressive hemicraniectomy to reduce intracranial pressure and to avoid uncal herniation. PML is a demyelinating disease of the central nervous system (CNS) which affects oligodendrocytes and is caused by reactivation of latent John Cunningham virus. Natalizumab is a known risk factor (1 in 1000) for MS patients treated with this drug. Discontinuation of natalizumab treatment decreases the risk of PML progression, but a massive inflammatory response can occur after cell-mediated immune surveillance is reestablished in the CNS, causing immune reconstitution inflammatory syndrome (IRIS). Treatment of IRIS usually consists of steroids and plasma exchange to lessen the immune response, however, mortality has been reported at up to 29.4%, despite aggressive medical treatment. We discuss our management strategy with a review of the pertinent literature. PMID:26115897

  19. Cardiorenal Syndrome Type 5: In Vitro Cytotoxicity Effects on Renal Tubular Cells and Inflammatory Profile

    PubMed Central

    Brocca, Alessandra; Virzì, Grazia Maria; Pasqualin, Chiara; Pastori, Silvia; Marcante, Stefano; de Cal, Massimo; Ronco, Claudio

    2015-01-01

    Background. Cardiorenal Syndrome Type 5 (CRS Type 5) reflects concomitant cardiac and renal dysfunctions in the setting of a wide spectrum of systemic disorders. Our aim was to study in vitro effects of CRS Type 5 plasma on renal tubular cells (RTCs), in terms of cellular death and the characterization of inflammatory plasma profile in these patients. Material and Methods. We enrolled 11 CRS Type 5 patients from ICU and 16 healthy controls. Plasma from patients and controls was incubated with renal tubular cells (RTCs) and cell death was evaluated. Plasma cytokines were detected. Results. RTCs incubated with CRS Type 5 plasma showed significantly higher apoptosis and necrosis with respect to controls. Plasma cytokine profile of CRS Type 5 patients was significantly different from controls: we observed the production of pro- and anti-inflammatory mediators in these patients. Caspase-3, caspase-8, and caspase-9 were activated in cells treated with CRS Type 5 plasma compared to controls. Conclusions. Our results underline the cytotoxic effect of CRS Type 5 mediators on RTC viability, probably due to the activation of both intrinsic and extrinsic pathways of apoptosis and to the deregulation of cytokine release. The consequence may be the damage of distant organs which lead to the worsening of condition of patients. PMID:26266085

  20. Immune reconstitution inflammatory syndrome in association with HIV/AIDS and tuberculosis: Views over hidden possibilities

    PubMed Central

    Shankar, Esaki Muthu; Vignesh, Ramachandran; Murugavel, Kailapuri G; Balakrishnan, Pachamuthu; Sekar, Ramalingam; Lloyd, Charmaine AC; Solomon, Suniti; Kumarasamy, Nagalingeswaran

    2007-01-01

    Gut immune components are severely compromised among persons with AIDS, which allows increased translocation of bacterial lipopolysaccharides (LPS) into the systemic circulation. These microbial LPS are reportedly increased in chronically HIV-infected individuals and findings have correlated convincingly with measures of immune activation. Immune reconstitution inflammatory syndrome (IRIS) is an adverse consequence of the restoration of pathogen-specific immune responses in a subset of HIV-infected subjects with underlying latent infections during the initial months of highly active antiretroviral treatment (HAART). Whether IRIS is the result of a response to a high antigen burden, an excessive response by the recovering immune system, exacerbated production of pro-inflammatory cytokines or a lack of immune regulation due to inability to produce regulatory cytokines remains to be determined. We theorize that those who develop IRIS have a high burden of proinflammatory cytokines produced also in response to systemic bacterial LPS that nonspecifically act on latent mycobacterial antigens. We also hypothesize that subjects that do not develop IRIS could have developed either tolerance (anergy) to persistent LPS/tubercle antigens or could have normal FOXP3+ gene and that those with defective FOXP3+ gene or those with enormous plasma LPS could be vulnerable to IRIS. The measure of microbial LPS, anti-LPS antibodies and nonspecific plasma cytokines in subjects on HAART shall predict the role of these components in IRIS. PMID:18053126

  1. Effects of SCR-3 on the immunosuppression accompanied with the systemic inflammatory response syndrome.

    PubMed

    Li, Jun; Niu, Jie; Ou, Shan; Ye, Zhan-Yong; Liu, Deng-Qun; Wang, Feng-Chao; Su, Yong-Ping; Wang, Jun-Ping

    2012-05-01

    Steroid receptor coactivator-3 (SRC-3) is a multifunctional protein that plays an important role in mammary gland growth, development, and tumorigenesis. In this study, SCR-3 gene knockout mice were used to study the effects of SCR-3 on the immunosuppression accompanied with systemic inflammatory response syndrome (SIRS). Bacterial clearance assay was performed by blood culture and frozen sections, and the results showed that the absence of SCR-3 protein serious damaged the innate immune system and the body's ability to inactivate or phagocytosis of bacteria was significantly decreased, and the absence of SCR-3 protein also weakened phagocytes' ability to degrade bacteria and their metabolites. Furthermore, animal model of inflammatory reaction was established and the immune function was determined, and the results revealed that SRC-3 protein may play an important role in maintenance of T-cells' immune function, and severe T-cell immune function disorder would be resulted once SRC-3 protein is missing. In addition, the results of our study showed the steady-state of lymphocyte subsets was destroyed after SIRS, leading the suppression of cellular immune function, and the absence of SCR-3 protein may aggravate the suppression of T-lymphocyte function. Therefore, the present study demonstrated that the absence of SCR-3 protein would aggravate immunosuppression. In addition, SRC-3 protein is a significant regulator of infection and inflammation, and SRC-3 protein play an essential role in the development of immunosuppression accompanied with SIRS.

  2. Symptomatology of irritable bowel syndrome and inflammatory bowel disease during the menstrual cycle.

    PubMed

    Bharadwaj, Shishira; Barber, Matthew D; Graff, Lesley A; Shen, Bo

    2015-08-01

    Gender-related physiological variations in gastrointestinal (GI) symptomatology have been observed in women of reproductive age. Many women experience cyclical changes in GI symptomatology during their menstrual cycle, particularly alteration in their bowel habits. Physiological studies of healthy women during the menstrual cycle showed a prolonged GI transit time during the luteal phase, either in the oro-cecum route or in the colon. Worsened GI symptoms, such as abdominal pain, bloating or diarrhea are observed in patients with irritable bowel syndrome (IBS) during menses. This may be due to elevated prostaglandin levels during menses, with an enhanced perception of viscera-somatic stimuli resulting in nausea, abdominal distension and pain. Also patients with IBS or IBD demonstrate a cyclical pattern more closely related to their bowel habits than healthy controls. Women with inflammatory bowel disease (IBD) also have exacerbated symptoms during menses; however, it is unclear whether this relates to physiological variation or disease exacerbation in IBS or IBD. Studies examining the association of the menstrual cycle and GI symptomatology in patients with IBS or IBD, have not yet clarified the underlying mechanisms. Moreover medications-such as non-steroidal anti-inflammatory drugs and oral contraceptive pills used for dysmenorrhea and menstrual migraine in those patients have not well been controlled for in the previous studies, which can contribute to further bias. Understanding changes in GI symptomatology during the menstrual cycle may help to determine the true extent of disease exacerbation and proper management strategy. PMID:25788484

  3. Is Xanthine oxidase activity in polycystic ovary syndrome associated with inflammatory and cardiovascular risk factors?

    PubMed

    Isık, Hatice; Aynıoglu, Oner; Tımur, Hakan; Sahbaz, Ahmet; Harma, Muge; Can, Murat; Guven, Berrak; Alptekin, Husnu; Kokturk, Furuzan

    2016-08-01

    The aim of this study is to examine women with polycystic ovary syndrome (PCOS) to determine the relationship between xanthine oxidase (XO) and oxidative stress, inflammatory status, and various clinical and biochemical parameters. In this cross-sectional study a total of 83 women including 45 PCOS patients and 38 healthy women were enrolled. We collected blood samples for XO and superoxide dismutase (SOD) activity, hormone levels, cholesterol values, and inflammatory markers. Body mass index (BMI) , waist-to-hip ratio (WHR), and blood pressure were assessed. Blood samples were taken for hormonal levels, cholesterol levels, fasting plasma glucose (FPG), fasting plasma insulin (FPI), homeostatic model assessment-insulin resistance (HOMA-IR) index, quantitative insulin sensitivity check index (QUICKI), C-reactive protein (CRP), white blood cell and neutrophil counts, XO and SOD activities. The basal hormone levels, triglyceride (TG) levels, TG/HDL-C (high density lipoprotein-cholesterol) ratios FPG, FPI and HOMA-IR levels were higher in PCOS patients compared to controls (p<0.05). Platelet and plateletcrit (PCT) values, CRP, and XO activity were significantly increased, however SOD activity was decreased in PCOS patients (p<0.001). XO activity was positively correlated with LH/FSH and TG/HDL ratios, CRP, PCT, FPG, FPI, and HOMA-IR, and negatively correlated with QUICKI levels. In conclusion, XO is a useful marker to assess oxidative stress in PCOS patients. Positive correlations between XO and inflammatory markers and cardiovascular disease risk factors suggest that XO plays an important role in the pathogenesis of PCOS and its metabolic complications. PMID:27295433

  4. Colchicine Acutely Suppresses Local Cardiac Production of Inflammatory Cytokines in Patients With an Acute Coronary Syndrome

    PubMed Central

    Martínez, Gonzalo J; Robertson, Stacy; Barraclough, Jennifer; Xia, Qiong; Mallat, Ziad; Bursill, Christina; Celermajer, David S; Patel, Sanjay

    2015-01-01

    Background Interleukin (IL)-1β, IL-18, and downstream IL-6 are key inflammatory cytokines in the pathogenesis of coronary artery disease. Colchicine is believed to block the NLRP3 inflammasome, a cytosolic complex responsible for the production of IL-1β and IL-18. In vivo effects of colchicine on cardiac cytokine release have not been previously studied. This study aimed to (1) assess the local cardiac production of inflammatory cytokines in patients with acute coronary syndromes (ACS), stable coronary artery disease and in controls; and (2) determine whether acute administration of colchicine inhibits their production. Methods and Results Forty ACS patients, 33 with stable coronary artery disease, and 10 controls, were included. ACS and stable coronary artery disease patients were randomized to oral colchicine treatment (1 mg followed by 0.5 mg 1 hour later) or no colchicine, 6 to 24 hours prior to cardiac catheterization. Blood samples from the coronary sinus, aortic root (arterial), and lower right atrium (venous) were collected and tested for IL-1β, IL-18, and IL-6 using ELISA. In ACS patients, coronary sinus levels of IL-1β, IL-18, and IL-6 were significantly higher than arterial and venous levels (P=0.017, <0.001 and <0.001, respectively). Transcoronary (coronary sinus-arterial) gradients for IL-1β, IL-18, and IL-6 were highest in ACS patients and lowest in controls (P=0.077, 0.033, and 0.014, respectively). Colchicine administration significantly reduced transcoronary gradients of all 3 cytokines in ACS patients by 40% to 88% (P=0.028, 0.032, and 0.032, for IL-1β, IL-18, and IL-6, respectively). Conclusions ACS patients exhibit increased local cardiac production of inflammatory cytokines. Short-term colchicine administration rapidly and significantly reduces levels of these cytokines. PMID:26304941

  5. Hypothalamus-Pituitary-Adrenal cell-mediated immunity regulation in the Immune Restoration Inflammatory Syndrome

    PubMed Central

    Khakshooy, Allen; Chiappelli, Francesco

    2016-01-01

    Over one third of the patients sero-positive for the human immunodeficiency virus (HIV) with signs of the acquired immune deficiency syndrome (AIDS), and under treatment with anti-retroviral therapy (ART), develop the immune reconstitution inflammatory syndrome (IRIS). It is not clear what variables are that determine whether a patient with HIV/AIDS will develop ART-related IRIS, but the best evidence base thus far indicates that HIV/AIDS patients with low CD4 cell count, and HIV/AIDS patients whose CD4 count recovery shows a sharp slope, suggesting a particularly fast "immune reconstitution", are at greater risk of developing IRIS. Here, we propose the hypothesis that one important variable that can contribute to low CD4 cell count number and function in ART-treated HIV/AIDS patients is altered hypothalamic-pituitary-adrenal (HPA) cell-mediated immune (CMI) regulation. We discuss HPA-CMI deregulation in IRIS as the new frontier in comparative effectiveness research (CRE) for obtaining and utilizing the best evidence base for treatment of patients with HIV/AIDS in specific clinical settings. We propose that our hypothesis about altered HPA-CMI may extend to the pathologies observed in related viral infection, including Zika PMID:27212842

  6. Risk of inflammatory bowel disease following a diagnosis of irritable bowel syndrome

    PubMed Central

    2012-01-01

    Background Irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) symptoms often overlap. In some IBS cases there are subtle inflammatory changes similar to the immune-mediated pathophysiology of IBD, and the risk of both increases after infectious gastroenteritis (IGE). Methods To evaluate the effect of IBS and IGE on IBD risk utilizing US Department of Defense medical encounter data, active duty personnel with IBS were matched to subjects without IBS. Medical encounter history was analyzed to assess for incident IBD. IGE was identified from documented medical encounters and by self-report. Relative risks were calculated using Poisson regression models. Results We identified 9,341 incident IBS cases and 18,678 matched non-IBS subjects and found an 8.6-fold higher incidence (p < 0.0001) of IBD among those with IBS (238.1 per 100,000 person-years) compared to our referent population (27.8 per 100,000 person-years). In a subset (n = 2,205) of well-defined IBS cases, IBD risk was 15 times that of subjects without IBS. The median time between IBS and IBD diagnoses was 2.1 years. IGE also increased IBD risk approximately 2-fold ( p < 0.05) after controlling for IBS. Conclusions These data reflect a complex interaction between illness presentation and diagnosis of IBS and IBD and suggest intercurrent IGE may increase IBD risk in IBS patients. Additional studies are needed to determine whether IBS lies on the causal pathway for IBD or whether the two are on a pathophysiological spectrum of the same clinical illness. These data suggest consideration of risk reduction interventions for IGE among IBS patients at high disease risk. PMID:22639930

  7. Correlation Between Bladder Pain Syndrome/Interstitial Cystitis and Pelvic Inflammatory Disease

    PubMed Central

    Chung, Shiu-Dong; Chang, Chao-Hsiang; Hung, Peir-Haur; Chung, Chi-Jung; Muo, Chih-Hsin; Huang, Chao-Yuan

    2015-01-01

    Abstract Pelvic inflammatory disease (PID) has been investigated in Western countries and identified to be associated with chronic pelvic pain and inflammation. Bladder pain syndrome/interstitial cystitis (BPS/IC) is a complex syndrome that is significantly more prevalent in women than in men. Chronic pelvic pain is a main symptom of BPS/IC, and chronic inflammation is a major etiology of BPS/IC. This study aimed to investigate the correlation between BPS/IC and PID using a population-based dataset. We constructed a case–control study from the Taiwan National Health Insurance program. The case cohort comprised 449 patients with BPS/IC, and 1796 randomly selected subjects (about 1:4 matching) were used as controls. A Multivariate logistic regression model was constructed to estimate the association between BPS/IC and PID. Of the 2245 sampled subjects, a significant difference was observed in the prevalence of PID between BPS/IC cases and controls (41.7% vs 15.4%, P < 0.001). Multivariate logistic regression analysis revealed that the odds ratio (OR) for PID among cases was 3.69 (95% confidence interval [CI]: 2.89–4.71). Furthermore, the ORs for PID among BPS/IC cases were 4.52 (95% CI: 2.55–8.01), 4.31 (95% CI: 2.91–6.38), 3.00 (95% CI: 1.82–4.94), and 5.35 (95% CI: 1.88–15.20) in the <35, 35–49, 50–64, and >65 years age groups, respectively, after adjusting for geographic region, irritable bowel syndrome, and hypertension. Joint effect was also noted, specifically when patients had both PID and irritable bowel disease with OR of 10.5 (95% CI: 4.88–22.50). This study demonstrated a correlation between PID and BPS/IC. Clinicians treating women with PID should be alert to BPS/IC-related symptoms in the population. PMID:26579800

  8. Managing Sjögren’s Syndrome and non-Sjögren Syndrome dry eye with anti-inflammatory therapy

    PubMed Central

    Coursey, Terry G; de Paiva, Cintia S

    2014-01-01

    Dry eye from Sjögren’s syndrome is a multifactorial disease that results in dysfunction of the lacrimal functional unit. Studies have shown changes in tear composition, including inflammatory cytokines, chemokines, and metalloproteinase. T-lymphocytes have been shown to increase in the conjunctiva and lacrimal glands in patient and animal models. This inflammation is in part responsible for the pathogenesis of the disease, which results in symptoms of eye irritation, ocular surface epithelial disease, and loss of corneal barrier function. There are a number of anti-inflammatory approaches for treating this disease. The current study reviews details of immune response and anti–inflammatory therapies used to control this disease. PMID:25120351

  9. Hyperperfusion in progressive multifocal leukoencephalopathy is associated with disease progression and absence of immune reconstitution inflammatory syndrome

    PubMed Central

    Khoury, Michael N.; Gheuens, Sarah; Ngo, Long; Wang, Xiaoen; Alsop, David C.

    2013-01-01

    We sought to characterize perfusion patterns of progressive multifocal leukoencephalopathy lesions by arterial spin labelling perfusion magnetic resonance imaging and to analyse their association with immune reconstitution inflammatory syndrome, and survival. A total of 22 patients with progressive multifocal leukoencephalopathy underwent a clinical evaluation and magnetic resonance imaging of the brain within 190 days of symptom onset. The presence of immune reconstitution inflammatory syndrome was determined based on clinical and laboratory criteria. Perfusion within progressive multifocal leukoencephalopathy lesions was determined by arterial spin labelling magnetic resonance imaging. We observed intense hyperperfusion within and at the edge of progressive multifocal leukoencephalopathy lesions in a subset of subjects. This hyperperfusion was quantified by measuring the fraction of lesion volume showing perfusion in excess of twice normal appearing grey matter. Hyperperfused lesion fraction was significantly greater in progressive multifocal leukoencephalopathy progressors than in survivors (12.8% versus 3.4% P = 0.02) corresponding to a relative risk of progression for individuals with a hyperperfused lesion fraction ≥ 4.0% of 9.1 (95% confidence interval of 1.4–59.5). The presence of hyperperfusion was inversely related to the occurrence of immune reconstitution inflammatory syndrome at the time of scan (P = 0.03). Indeed, within 3 months after symptom onset, hyperperfusion had a positive predictive value of 88% for absence of immune reconstitution inflammatory syndrome. Arterial spin labelling magnetic resonance imaging recognized regions of elevated perfusion within lesions of progressive multifocal leukoencephalopathy. These regions might represent virologically active areas operating in the absence of an effective adaptive immune response and correspond with a worse prognosis. PMID:24088807

  10. A new method to detect systemic inflammatory response syndrome by continuous monitoring system: an experimental study in rats.

    PubMed

    Matsui, T; Ishizuka, T; Ishihara, M; Suzuki, M; Kurita, A; Kikuchi, M

    2005-01-01

    A continuous monitoring system was designed for detection of systemic inflammatory response syndrome (SIRS) using spectrum analyser and local temperature mapping system with deep body thermometer. This method demonstrated significant increases of heart and respiratory rates and deep body temperature from normal levels within 120 minutes after lipopolysaccharide administration in rats. Our monitoring system appears promising for clinical detection of SIRS in the early stages to prevent multiple organ failure. PMID:15764377

  11. [Influence of systemic inflammatory response syndrome on the pharmacokinetics of vancomycin].

    PubMed

    Irikuchi, Jinshi; Imai, Toru; Yoshida, Yoshikazu; Orii, Takao

    2015-01-01

    Therapeutic drug monitoring (TDM) of vancomycin (VCM) is recommended to minimize its nephrotoxicity and maximize efficacy. Recently, the concept of systemic inflammatory response syndrome (SIRS) has been introduced to describe a clinical state resulting from the actions of complex intrinsic mediators in an acute-phase systemic response. However, there are few reports on the pharmacokinetics of VCM in patients with SIRS. This study investigated the effect of SIRS on the pharmacokinetics of VCM by analyzing the predictability of TDM and pharmacokinetic parameters in 31 non-SIRS patients and 52 SIRS patients, with stratification by SIRS score. The mean prediction error (ME) and mean absolute prediction error in SIRS score 2 and 3 patients differed from those in non-SIRS patients. The ME in the score 4 group showed a negative value. In the comparison of pharmacokinetic parameters by SIRS score, a significantly lower CL(vcm) value was observed at score 4 compared with scores 2 and 3, a higher Vd value was observed at score 4 compared with non-SIRS and at score 3, and a longer T1/2 was observed at score 2. In the comparison of patient characteristics by SIRS score, albumin, aspartate aminotransferase, and alanine aminotransferase levels showed differences among the scores. However, no correlation was observed between VCM pharmacokinetics and these three laboratory parameters. These findings suggest that the pharmacokinetics of VCM may be affected by the pathology of SIRS rather than by patient characteristics.

  12. The anti-inflammatory effects of exercise in the syndromic thread of diabetes and autoimmunity.

    PubMed

    Codella, R; Luzi, L; Inverardi, L; Ricordi, C

    2015-10-01

    A unifying thread over the wide spectrum of diabetes might be the triggering of innate immunological and inflammatory pathways leading to insulin resistance, beta-cell dysfunction and beta-cell destruction: the hybrid features of type 1 and type 2 diabetes. In fact, hyperglycemia can arise from a deficit in insulin action, insulin secretion, or both. Regularly exercising at moderate intensity has been shown to efficiently and positively impact upon physiological imbalances caused by several morbid conditions. Even in different immunological dysfunctions, physical exercise has been prescribed as a complementary therapeutic strategy. In fact, as suggested by our observations, there is a putative inverse relationship between autoimmunity markers (GAD, IA) and exercise-derived energy expenditure in type 1 pre-diabetic subjects. Exercise also has been shown to maintain muscle mitochondrial function and thus ability to maintain fuel metabolism and islet cell function. An additional benefit is the enhancement of antioxidant defense system and thus reducing oxidative stress. Therefore, the purpose of this review is to address the importance of physical exercise in a broad range of metabolic disorders that set out a common milieu in which type 1 and type 2 diabetes could be identified as one extensive syndrome. PMID:26502862

  13. Germline NLRP1 Mutations Cause Skin Inflammatory and Cancer Susceptibility Syndromes via Inflammasome Activation.

    PubMed

    Zhong, Franklin L; Mamaï, Ons; Sborgi, Lorenzo; Boussofara, Lobna; Hopkins, Richard; Robinson, Kim; Szeverényi, Ildikó; Takeichi, Takuya; Balaji, Reshmaa; Lau, Aristotle; Tye, Hazel; Roy, Keya; Bonnard, Carine; Ahl, Patricia J; Jones, Leigh Ann; Baker, Paul; Lacina, Lukas; Otsuka, Atsushi; Fournie, Pierre R; Malecaze, François; Lane, E Birgitte; Akiyama, Masashi; Kabashima, Kenji; Connolly, John E; Masters, Seth L; Soler, Vincent J; Omar, Salma Samir; McGrath, John A; Nedelcu, Roxana; Gribaa, Moez; Denguezli, Mohamed; Saad, Ali; Hiller, Sebastian; Reversade, Bruno

    2016-09-22

    Inflammasome complexes function as key innate immune effectors that trigger inflammation in response to pathogen- and danger-associated signals. Here, we report that germline mutations in the inflammasome sensor NLRP1 cause two overlapping skin disorders: multiple self-healing palmoplantar carcinoma (MSPC) and familial keratosis lichenoides chronica (FKLC). We find that NLRP1 is the most prominent inflammasome sensor in human skin, and all pathogenic NLRP1 mutations are gain-of-function alleles that predispose to inflammasome activation. Mechanistically, NLRP1 mutations lead to increased self-oligomerization by disrupting the PYD and LRR domains, which are essential in maintaining NLRP1 as an inactive monomer. Primary keratinocytes from patients experience spontaneous inflammasome activation and paracrine IL-1 signaling, which is sufficient to cause skin inflammation and epidermal hyperplasia. Our findings establish a group of non-fever inflammasome disorders, uncover an unexpected auto-inhibitory function for the pyrin domain, and provide the first genetic evidence linking NLRP1 to skin inflammatory syndromes and skin cancer predisposition. PMID:27662089

  14. Idiopathic Inflammatory Myopathies and the Anti-Synthetase Syndrome: A Comprehensive Review

    PubMed Central

    Mahler, Michael; Miller, Frederick W.; Fritzler, Marvin J.

    2014-01-01

    Autoantibodies are a hallmark in the diagnosis of many systemic autoimmune rheumatic diseases (SARD) including idiopathic inflammatory myopathies (IIM). Based on their specificity, autoantibodies in IIM are grouped into myositis specific (MSA) and myositis associated autoantibodies (MAA). Among the MSA, autoantibodies against aminoacyl-tRNA synthetases (ARS) represent the most common antibodies and can be detected in 25–35 % of patients. The presence of ARS and other autoantibodies have become a key feature for classification and diagnosis of IIM and are increasingly used to define clinically distinguishable IIM subsets. For example, anti-ARS autoantibodies are the key features of what has become known as anti-synthetase syndrome (aSS), characterized by multiple organ involvement, primarily interstitial lung disease, often accompanied by myositis, non-erosive arthritis, Raynaud’s phenomenon, fever, and “mechanic’s hands”. Autoantibodies directed to eight different ARS have been described: Jo-1 (histidyl), PL-7 (threonyl), PL-12 (alanyl), OJ (isoleucyl), EJ (glycyl), KS (asparaginyl), Zo (phenylalanyl) and Ha (tyrosyl). Each anti-ARS antibody seems to define a distinctive clinical phenotype. Although several research methods and commercial tests are available, routine testing for anti-ARS autoantibodies (other than anti-Jo-1/histidyl-tRNA synthetase) is not widely available, sometimes leading to delays in diagnosis and poor disease outcomes. PMID:24424190

  15. Morphological changes of an inflammatory myopathy in rhesus monkeys with simian acquired immunodeficiency syndrome.

    PubMed

    Dalakas, M C; Gravell, M; London, W T; Cunningham, G; Sever, J L

    1987-09-01

    Eleven of 25 rhesus monkeys which died of simian acquired immunodeficiency syndrome (SAIDS) caused by infection with a type D retrovirus related to Mason-Pfizer monkey virus showed evidence of muscle weakness and atrophy and had elevated levels of muscle enzymes. Biopsies of affected muscle studied with enzyme histochemistry showed the characteristic features of polymyositis. Inflammatory cells consisting of lymphocytes, macrophages, and large vacuolated bizarre-shaped cells of undetermined type were surrounding or invading muscle fibers and were present in the perivascular spaces and endomysia septa. Within the perivascular infiltrates, lymphocytes were abundant but very few macrophages were present. Other myopathic features including profound proliferation of fibrous tissue, necrosis, and phagocytosis of muscle fibers were noted to a variable degree. The retrovirus was isolated from affected muscles. The clinical and historical features of polymyositis in rhesus monkeys with SAIDS are very similar to those of human polymyositis. The polymyositis in SAIDS induced by a type D retrovirus related to Mason-Pfizer monkey virus is an excellent primate model to study the mechanism and morphological changes of viral-induced muscle damage.

  16. Nivolumab-induced chronic inflammatory demyelinating polyradiculoneuropathy mimicking rapid-onset Guillain-Barré syndrome: a case report.

    PubMed

    Tanaka, Ryota; Maruyama, Hiroshi; Tomidokoro, Yasushi; Yanagiha, Kumi; Hirabayashi, Takumi; Ishii, Akiko; Okune, Mari; Inoue, Sae; Sekine, Ikuo; Tamaoka, Akira; Fujimoto, Manabu

    2016-09-01

    Nivolumab, an anti-programmed death-1-specific monoclonal antibody, has demonstrated a durable response and effect on overall survival and has become one of the standard treatments for patients with advanced melanoma. Reported herein is a case of nivolumab-induced chronic inflammatory demyelinating polyradiculoneuropathy, in which an 85-year-old woman with stage IV melanoma developed grade 1 paresthesia 2 weeks after the initial dose of nivolumab was administered. With continued treatment, the neurological deficiency deteriorated rapidly, mimicking Guillain-Barré syndrome, causing such a dramatic decrease in her activities of daily living that she could no longer function in daily life. Thus, nivolumab treatment was discontinued. A course of intravenous immunoglobulin infusion yielded a dramatic clinical improvement; in particular, improved motor control was observed within a few days. Her initial presentation was suggestive of acute inflammatory demyelinating polyradiculoneuropathy, a subtype of Guillain-Barré syndrome; however, the good response to steroids and exacerbation 8 weeks after the onset were suggestive of chronic inflammatory demyelinating polyradiculoneuropathy induced by nivolumab. This is the first case of Guillain-Barré syndrome-like autoimmune polyradiculoneuropathy induced by programmed death-1/programmed death-ligand 1 inhibitors. Although neurological adverse events related to nivolumab are rare, they can become severe, requiring early diagnosis and intervention. Intravenous immunoglobulin may be considered as an effective initial treatment for patients who develop acute autoimmune nervous system disorders due to nivolumab.

  17. Red wine extract decreases pro-inflammatory markers, nuclear factor-κB and inducible NOS, in experimental metabolic syndrome.

    PubMed

    Janega, Pavol; Klimentová, Jana; Barta, Andrej; Kovácsová, Mária; Vranková, Stanislava; Cebová, Martina; Čierna, Zuzana; Matúsková, Zuzana; Jakovljevic, Vladimir; Pechánová, Olga

    2014-09-01

    We aimed to analyse the effects of alcohol-free Alibernet red wine extract (AWE) on nitric oxide synthase (NOS) activity and pro-inflammatory markers such as nuclear factor-κB (NFκB) and inducible NOS (iNOS) protein expression in experimental metabolic syndrome. Young 6 week-old male Wistar Kyoto (WKY) and obese, spontaneously hypertensive rats (SHR/N-cp) were divided into control groups and groups treated with AWE (24.2 mg per kg per day) for 3 weeks (n = 6 in each group). Total NOS activity and endothelial NOS (eNOS), iNOS and NFκB (p65) protein expressions were determined in the heart left ventricle and aorta by Western blot and immunohistochemical analysis. All parameters investigated significantly increased in the aorta of SHR/N-cp rats. Pro-inflammatory markers such as NFκB and iNOS were increased in the left ventricle as well. AWE treatment did not affect total NOS activity and eNOS expression in the aorta; however, it was able to decrease NFκB and iNOS protein expression in both the left ventricle and aorta. In conclusion, in the cardiovascular system, Alibernet red wine extract decreased NFκB and iNOS protein expressions elevated as a consequence of developed metabolic syndrome. This effect may represent one of the protective, anti-inflammatory properties of Alibernet red wine polyphenols on cardiovascular risk factors related to metabolic syndrome.

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

    PubMed Central

    2010-01-01

    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. PMID:20109187

  19. The use of imaging technology in the assessment of the fetal inflammatory response syndrome-imaging of the fetal thymus.

    PubMed

    Sciaky-Tamir, Yael; Hershkovitz, Reli; Mazor, Moshe; Shelef, Ilan; Erez, Offer

    2015-05-01

    The fetal inflammatory response syndrome (FIRS) describes a state of extensive fetal multi organ involvement during chorioamnionitis, and is associated with grave implications on perinatal outcome. The syndrome has been linked to the preterm parturition syndrome and is associated with inflammation/infection processes in most of the fetal organs. The fetal thymus, a major organ in the developing immune system involutes during severe neonatal disease and has been shown to be smaller in fetuses with FIRS. Various methods for imaging of the fetal thymus and measurement are described. Currently the only method to diagnose FIRS prenatally is through amniocentesis. We suggest that women who are admitted with preterm labor with intact membranes and those with PPROM should have a detailed sonographic examination of the fetal thymus as a surrogate marker of fetal involvement in intrauterine infection/inflammation processes.

  20. Systemic inflammatory response syndrome in adult patients with nosocomial bloodstream infections due to enterococci

    PubMed Central

    Bar, Katharine; Wisplinghoff, Hilmar; Wenzel, Richard P; Bearman, Gonzalo ML; Edmond, Michael B

    2006-01-01

    Background Enterococci are the third leading cause of nosocomial bloodstream infection (BSI). Vancomycin resistant enterococci are common and provide treatment challenges; however questions remain about VRE's pathogenicity and its direct clinical impact. This study analyzed the inflammatory response of Enterococcal BSI, contrasting infections from vancomycin-resistant and vancomycin-susceptible isolates. Methods We performed a historical cohort study on 50 adults with enterococcal BSI to evaluate the associated systemic inflammatory response syndrome (SIRS) and mortality. We examined SIRS scores 2 days prior through 14 days after the first positive blood culture. Vancomycin resistant (n = 17) and susceptible infections (n = 33) were compared. Variables significant in univariate analysis were entered into a logistic regression model to determine the affect on mortality. Results 60% of BSI were caused by E. faecalis and 34% by E. faecium. 34% of the isolates were vancomycin resistant. Mean APACHE II (A2) score on the day of BSI was 16. Appropriate antimicrobials were begun within 24 hours in 52%. Septic shock occurred in 62% and severe sepsis in an additional 18%. Incidence of organ failure was as follows: respiratory 42%, renal 48%, hematologic 44%, hepatic 26%. Crude mortality was 48%. Progression to septic shock was associated with death (OR 14.9, p < .001). There was no difference in A2 scores on days -2, -1 and 0 between the VRE and VSE groups. Maximal SIR (severe sepsis, septic shock or death) was seen on day 2 for VSE BSI vs. day 8 for VRE. No significant difference was noted in the incidence of organ failure, 7-day or overall mortality between the two groups. Univariate analysis revealed that AP2>18 at BSI onset, and respiratory, cardiovascular, renal, hematologic and hepatic failure were associated with death, but time to appropriate therapy >24 hours, age, and infection due to VRE were not. Multivariate analysis revealed that hematologic (OR 8.4, p = .025

  1. Circulating Plasma microRNAs can differentiate Human Sepsis and Systemic Inflammatory Response Syndrome (SIRS)

    PubMed Central

    Caserta, Stefano; Kern, Florian; Cohen, Jonathan; Drage, Stephen; Newbury, Sarah F.; Llewelyn, Martin J.

    2016-01-01

    Systemic inflammation in humans may be triggered by infection, termed sepsis, or non-infective processes, termed non-infective systemic inflammatory response syndrome (SIRS). MicroRNAs regulate cellular processes including inflammation and may be detected in blood. We aimed to establish definitive proof-of-principle that circulating microRNAs are differentially affected during sepsis and non-infective SIRS. Critically ill patients with severe (n = 21) or non-severe (n = 8) intra-abdominal sepsis; severe (n = 23) or non-severe (n = 21) non-infective SIRS; or no SIRS (n = 16) were studied. Next-generation sequencing and qRT-PCR were used to measure plasma microRNAs. Detectable blood miRNAs (n = 116) were generally up-regulated in SIRS compared to no-SIRS patients. Levels of these ‘circulating inflammation-related microRNAs’ (CIR-miRNAs) were 2.64 (IQR: 2.10–3.29) and 1.52 (IQR: 1.15–1.92) fold higher for non-infective SIRS and sepsis respectively (p < 0.0001), hence CIR-miRNAs appeared less abundant in sepsis than in SIRS. Six CIR-miRNAs (miR-30d-5p, miR-30a-5p, miR-192-5p, miR-26a-5p, miR-23a-5p, miR-191-5p) provided good-to-excellent discrimination of severe sepsis from severe SIRS (0.742–0.917 AUC of ROC curves). CIR-miRNA levels inversely correlated with pro-inflammatory cytokines (IL-1, IL-6 and others). Thus, among critically ill patients, sepsis and non-infective SIRS are associated with substantial, differential changes in CIR-miRNAs. CIR-miRNAs may be regulators of inflammation and warrant thorough evaluation as diagnostic and therapeutic targets. PMID:27320175

  2. Systemic inflammatory response syndrome and prolonged hypoperfusion lesions in an infant with respiratory syncytial virus encephalopathy.

    PubMed

    Miyamoto, Kenji; Fujisawa, Masahide; Hozumi, Hajime; Tsuboi, Tatsuo; Kuwashima, Shigeko; Hirao, Jun-ichi; Sugita, Kenichi; Arisaka, Osamu

    2013-10-01

    Respiratory syncytial virus (RSV) is a cause of neurological complications in infants. We report a rare case of RSV encephalopathy in an infant who presented with poor sucking and hypothermia at 17 days of age after suffering from rhinorrhea and a cough for several days. After hospitalization, the patient presented with stupor and hypotonia lasting for at least 24 h, and was intubated, sedated, and ventilated for treatment of pneumonia. These symptoms led to diagnosis of pediatric systemic inflammatory response syndrome (SIRS) caused by RSV infection. High-dose steroid therapy was combined with artificial ventilation because the initial ventilation therapy was ineffective. Interleukin (IL)-6 levels in spinal fluid were markedly increased upon admission, and serum IL-6 and IL-8 levels showed even greater elevation. The patient was diagnosed with RSV encephalopathy. On day 5, high signal intensity in the bilateral hippocampus was observed on diffusion-weighted magnetic resonance imaging (MRI). On day 14, the patient presented with delayed partial seizure and an electroencephalogram showed occasional unilateral spikes in the parietal area, but the hippocampal abnormality had improved to normal on MRI. (99m)Tc-labeled ethylcysteinate dimer single-photon emission computed tomography (SPECT) on day 18 showed hypoperfusion of the bilateral frontal and parietal regions and the unilateral temporal region. SPECT at 3 months after onset still showed hypoperfusion of the bilateral frontal region and unilateral temporal region, but hypoperfusion of the bilateral parietal region had improved. The patient has no neurological deficit at 6 months. These findings suggest that RSV encephalopathy with cytokine storm induces several symptoms and complications, including SIRS and prolonged brain hypoperfusion on SPECT.

  3. Profound systemic inflammatory response syndrome following non-emergent intestinal surgery in children☆

    PubMed Central

    Chawla, Bhani K.; Teitelbaum, Daniel H.

    2013-01-01

    Purpose Systemic inflammatory response syndrome (SIRS) is an uncommon but severe complication in surgical patients. While SIRS is well known, it is poorly described in the pediatric population. The goal of this study was to describe the incidence of profound SIRS following non-emergent intestinal surgery in children and to identify potential risk factors. Methods A retrospective review was conducted for patients 0–19 years of age following intestinal surgery and/or lysis of adhesions from 01/01/1999-02/28/2012. Children were excluded for preoperative instability or frank bowel perforation. Patients were then placed in a post-operative SIRS or non-SIRS group as defined by the 2005 International Pediatric Sepsis Consensus Conference Guidelines (6. B. Goldstein, B. Giroir, A. Randolph, and Sepsis International Consensus Conference on Pediatric, ‘International Pediatric Sepsis Consensus Conference: Definitions for Sepsis and Organ Dysfunction in Pediatrics’, Pediatr Crit Care Med, 6 (2005), 2–8.). Results SIRS was identified in 17 of the 381 patients. Logistic regression analysis was performed and showed heart disease, kidney disease, PN dependence, and intestinal obstruction to be predictive of post-operative SIRS. Conclusion This study represents one of the first reports to identify a previously poorly described process of significant SIRS after intestinal surgery in children. Both systemic organ failure and intestinal dysfunction are strong risk factors for post-operative SIRS in children. Potentially, these pre-existing conditions may lead to disruption of normal intestinal flora or barrier function, which in turn may predispose these children for dramatic SIRS after intestinal surgery. Understanding how these factors lead to SIRS will be critical to developing prevention strategies. PMID:24074671

  4. Prebiotics and probiotics in irritable bowel syndrome and inflammatory bowel disease in children.

    PubMed

    Guandalini, S; Cernat, E; Moscoso, D

    2015-01-01

    Underlying pathophysiological mechanisms of irritable bowel syndrome (IBS), a common disorder characterized by abdominal pain associated to a change in stool consistency or frequency, include low-grade inflammation and intestinal microbiota changes. Few and disappointing data are available for prebiotics. A few controlled trials (RCTs) of probiotics are instead available with favourable effects, although most are limited by suboptimal design and small sample size. A recent report from the Rome foundation group included 32 RCTs of probiotics, most of which showed an overall modest improvement in symptoms, with the patients most benefitting from probiotics being those with predominant diarrhoea and those having a post-infectious IBS. A review focusing only on children with functional gastrointestinal disorders concluded that probiotics are more effective than placebo in the treatment of patients with abdominal pain-related functional gastrointestinal disorders, although no effect on constipation was evident. The role for probiotics in inflammatory bowel disease (IBD) appears logical: the endogenous intestinal microbiota plays a central role in their development, and various probiotics have been found effective in animal models of IBD. However, research in humans has been overall quite limited, and it would seem that after a phase of intense research in the first decade of this century, the pace has slowed down, with fewer clinical trials been published in the past 2-3 years. To summarize current evidence: no probiotic has proven successful in Crohn's disease. In ulcerative colitis, on the other hand, data are more promising, and a very recent meta-analysis, that included 23 randomized controlled trials, concluded that there is evidence of efficacy for the probiotic mixture VSL#3 in helping inducing and maintaining remission, as well as in maintaining remission in patients with pouchitis. It is fair to state that for both IBD and IBS, more well-designed, rigorous

  5. Psychological adjustment and autonomic disturbances in inflammatory bowel diseases and irritable bowel syndrome.

    PubMed

    Pellissier, Sonia; Dantzer, Cécile; Canini, Fréderic; Mathieu, Nicolas; Bonaz, Bruno

    2010-06-01

    Psychological factors and the autonomic nervous system (ANS) are implicated in the pathogenesis of inflammatory bowel diseases (IBD) and irritable bowel syndrome (IBS). This study aimed to assess, firstly the way IBS and IBD patients cope with their pathology according to their affective adjustment and secondly the possible links between these affective adjustments and ANS reactivity. Patients with Crohn's disease (CD; n=26), ulcerative colitis (UC; n=22), or IBS (n=27) were recruited and compared to 21 healthy subjects based on psychological variables (trait- and state anxiety, depressive symptomatology, negative mood, perceived stress, coping, health locus of control) and sympatho-vagal balance through heart-rate variability monitored at rest. A principal component analysis, performed on all affective variables, isolated a leading factor labelled as "affective adjustment". In each disease, patients were distributed into positive and negative affective adjustment. In all the diseases, a positive affect was associated with problem-focused coping, and a negative affect with emotion-focused coping and external health locus of control. Results show that the sympatho-vagal balance varied according to the disease. In CD presenting positive affectivity, an adapted high sympathetic activity was observed. In UC, a parasympathetic blunt was observed in the presence of negative affectivity and an equilibrated sympatho-vagal balance in the presence of positive affectivity. In contrast, in IBS, an important dysautonomia (with high sympathetic and low parasympathetic tone) was constantly observed whatever the affective adjustment. In conclusion, this study suggests that the equilibrium of the ANS is differentially adapted according to the disease. This equilibrium is conjugated with positive affective and cognitive adjustment in IBD (CD and UC) but not in IBS.

  6. Overlapping irritable bowel syndrome and inflammatory bowel disease: less to this than meets the eye?

    PubMed Central

    Quigley, Eamonn M. M.

    2016-01-01

    Though distinct in terms of pathology, natural history and therapeutic approach, irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) have some features in common. These include shared symptomatology and largely similar demographics. However, in most instances, clinical presentation, together with laboratory, imaging and endoscopic findings will readily permit the differentiation of active IBD from IBS. More problematic is the situation where a subject with IBD, in apparent remission, continues to complain of symptoms which, in aggregate, satisfy commonly employed criteria for the diagnosis of IBS. Access to methodologies, such the assay for levels of calprotectin in feces, now allows identification of ongoing inflammation in some such individuals and prompts appropriate therapy. More challenging is the IBD patient with persisting symptoms and no detectable evidence of inflammation; is this coincident IBS, IBS triggered by IBD or an even more subtle level of IBD activity unrecognized by available laboratory or imaging methods? Arguments can be advanced for each of these proposals; lacking definitive data, this issue remains unresolved. The occurrence of IBS-type symptoms in the IBD patient, together with some data suggesting a very subtle level of ‘inflammation‘ or ‘immune activation‘ in IBS, raises other questions: is IBS a prodromal form of IBD; and are IBS and IBD part of the spectrum of the same disease? All of the available evidence indicates that the answer to both these questions should be a resounding ‘no’. Indeed, the whole issue of overlap between IBS and IBD should be declared moot given their differing pathophysiologies, contrasting natural histories and divergent treatment paths. The limited symptom repertoire of the gastrointestinal tract may well be fundamental to the apparent confusion that has, of late, bedeviled this area. PMID:26929782

  7. Postischemic inflammatory syndrome: a critical mechanism of progression in diabetic nephropathy.

    PubMed

    Kelly, K J; Burford, James L; Dominguez, Jesus H

    2009-10-01

    Diabetes is a major epidemic, and diabetic nephropathy is the most common cause of end-stage renal disease. Two critical components of diabetic nephropathy are persistent inflammation and chronic renal ischemia from widespread vasculopathy. Moreover, acute ischemic renal injury is common in diabetes, potentially causing chronic kidney disease or end-stage renal disease. Accordingly, we tested the hypothesis that acute renal ischemia accelerates nephropathy in diabetes by activating proinflammatory pathways. Lean and obese-diabetic ZS rats (F(1) hybrids of spontaneously hypertensive heart failure and Zucker fatty diabetic rats) were subjected to bilateral renal ischemia or sham surgery before the onset of proteinuria. The postischemic state in rats with obesity-diabetes was characterized by progressive chronic renal failure, increased proteinuria, and renal expression of proinflammatory mediators. Leukocyte number in obese-diabetic rat kidney was markedly increased for months after ischemia. Intrarenal blood flow velocity was decreased after ischemia in lean control and obese-diabetic rats, although it recovered in lean rats. At 2 mo after ischemia, blood flow velocity decreased further in sham-surgery and postischemia obese-diabetic rats, so that RBC flow velocity was only 39% of control in the obese-diabetic rats after ischemia. In addition, microvascular density remained depressed at 2 mo in kidneys of obese-diabetic rats after ischemia. Abnormal microvascular permeability and increases in interstitial fibrosis and apoptotic renal cell death were also more pronounced after ischemia in obese-diabetic rats. These data support the hypothesis that acute renal ischemia in obesity-diabetes severely aggravates chronic inflammation and vasculopathy, creating a self-perpetuating postischemia inflammatory syndrome, which accelerates renal failure.

  8. Idiopathic Pyoderma Gangrenosum as a Novel Manifestation of the HIV Immune Reconstitution Inflammatory Syndrome: A Report of Three Cases.

    PubMed

    Nambudiri, Vinod E; Kersellius, Romona; Harp, Joanna; Maniar, J K; Maurer, Toby A

    2015-07-01

    The initiation of antiretroviral treatment for individuals with HIV may be accompanied by a paradoxical flare of underlying inflammatory diseases, the recurrence of dormant infections, or worsening of prior treated opportunistic infections, termed the immune reconstitution inflammatory syndrome (IRIS). Cutaneous manifestations of IRIS are common. Pyoderma gangrenosum is a neutrophilic dermatosis postulated to reflect disrupted innate immune regulation causing altered neutrophil chemotaxis. It is uncommonly reported in association with HIV. In this case series, we present three cases of IRIS manifesting with pyoderma gangrenosum in individuals with HIV from India and the United States to raise awareness of this previously undescribed presentation and discuss the treatment challenges in the management of these patients. PMID:26731836

  9. Inflammatory cytokines regulate secretion of VEGF and chemokines by human conjunctival fibroblasts: Role in dysfunctional tear syndrome.

    PubMed

    Nagineni, Chandrasekharam N; William, Abitha; Cherukuri, Aswini; Samuel, William; Hooks, John J; Detrick, Barbara

    2016-02-01

    Ocular surface inflammation is one of the primary mechanisms associated with dysfunctional tear syndrome (DTS), also known as dry eye disease. DTS, more prevalent in older populations, causes ocular discomfort and visual disturbance due to dryness on the surface layer in the eye. We used human conjunctival fibroblast cultures (HCJVF) to investigate the effects of inflammatory cytokines IFN-γ, TNF-α and IL-1β (ITI) on the secretions of VEGF and chemokines. Our results demonstrate the elevated secretion of angiogenic VEGF molecules by ITI without affecting anti-angiogenic molecules, PEDF, endostatin, thrombospondin and sVEGF-R1. The secretion of interferon-γ inducible chemokines, CXCL9, -10, -11 by HCJVF were significantly enhanced by ITI. Our in vitro study supports previously reported observations of elevated VEGF and chemokines in tear fluids of DTS patients, reiterating the role of inflammatory reactions in DTS. PMID:26615568

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

    PubMed Central

    Morris, Gerwyn; Maes, Michael

    2014-01-01

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

  11. Metabolic Syndrome and Inflammatory Responses to Long-Term Particulate Air Pollutants

    PubMed Central

    Chen, Jiu-Chiuan; Schwartz, Joel

    2008-01-01

    Background Human data linking inflammation with long-term particulate matter (PM) exposure are still lacking. Emerging evidence suggests that people with metabolic syndrome (MS) may be a more susceptible population. Objectives Our goal was to examine potential inflammatory responses associated with long-term PM exposure and MS-dependent susceptibility. Methods We conducted secondary analyses of white blood cell (WBC) count and MS data from The Third National Health and Nutrition Examination Survey and PM10 (PM with aerodynamic diameter < 10 μm) data from the U.S. Environmental Protection Agency Aerometric Information Retrieval System. Estimated 1-year PM10 exposures were aggregated at the centroid of each residential census-block group, using distance-weighted averages from all monitors in the residing and adjoining counties. We restricted our analyses to adults (20–89 years of age) with normal WBC (4,000–11,000 × 106/L), no existing cardiovascular disease, complete PM10 and MS data, and living in current residences > 1 year (n = 2,978; age 48.5 ± 17.8 years). Mixed-effects models were constructed to account for autocorrelation and potential confounders. Results After adjustment for demographics, socioeconomic factors, lifestyles, residential characteristics, and MS, we observed a statistically significant association between WBC count and estimated local PM10 levels (p = 0.035). Participants from the least polluted areas (1-year PM10 < 1st quartile cutoff: 27.8 μg/m3) had lower WBC counts than the others (difference = 145 × 106/L; 95% confidence interval, 10–281). We also noted a graded association between PM10 and WBC across subpopulations with increasing MS components, with 91 × 106/L difference in WBC for those with no MS versus 214, 338, and 461 × 106/L for those with 3, 4, and 5 metabolic abnormalities (trend-test p = 0.15). Conclusions Our study revealed a positive association between long-term PM exposure and hematological markers of

  12. Chronic prehepatic portal hypertension in the rat: is it a type of Metabolic Inflammatory Syndrome?

    PubMed Central

    Sánchez-Patán, Fernando; Anchuelo, Raquel; Aller, Maria-Angeles; Vara, Elena; García, Cruz; Nava, Maria-Paz; Arias, Jaime

    2008-01-01

    Background A progressive development of hepatic steatosis with an increase in the lipid hepatocyte content and the formation of megamitochondria have been demonstrated in rats with prehepatic portal hypertension. The aim of this study is to verify the existence of liver and serum lipid metabolism impairments in rats with long-term (2 years) portal hypertension. Methods Male Wistar rats: Control (n = 10) and with prehepatic portal hypertension by triple partial portal vein ligation (n = 9) were used. Liver content of Triglycerides (TG), phospholipids (PL) and cholesterol and serum cholesterol, lipoproteins (HDL and LDL), TG, glucose and Lipid Binding Protein (LBP) were assayed with specific colorimetric commercial kits. Serum levels of insulin and somatostatin were assayed by RIA. Results The liver content of TG (6.30 ± 1.95 vs. 4.17 ± 0.59 μg/ml; p < 0.01) and cholesterol (1.48 ± 0.15 vs. 1.10 ± 0.13 μg/ml; p < 0.001) increased in rats with portal hypertension. The serum levels of cholesterol (97.00+26.02 vs. 114.78 ± 37.72 mg/dl), TG (153.41 ± 80.39 vs. 324.39 ± 134.9 mg/dl; p < 0.01), HDL (20.45 ± 5.14 vs. 55.15 ± 17.47 mg/dl; p < 0.001) and somatostatin (1.32 ± 0.31 vs. 1.59 +0.37 mg/dl) decreased, whereas LDL (37.83 ± 15.39 vs. 16.77 ± 6.81 mg/dl; p < 0.001) and LBP (308.47 ± 194.53 vs. 60.27 ± 42.96 ng/ml; p < 0.001) increased. Conclusion Portal hypertension in the rat presents changes in the lipid and carbohydrate metabolisms similar to those produced in chronic inflammatory conditions and sepsis in humans. These underlying alterations could be involved in the development of hepatic steatosis and, therefore, in those described in the metabolic syndrome in humans. PMID:18271959

  13. Primary sclerosing cholangitis, autoimmune hepatitis and overlap syndromes in inflammatory bowel disease

    PubMed Central

    Saich, Rebecca; Chapman, Roger

    2008-01-01

    Primary sclerosing cholangitis (PSC) is a chronic progressive disorder of unknown aetiology characterised by chronic inflammation and stricture formation of the biliary tree. Symptoms include itch and lethargy and in advanced cases cholangitis and end-stage liver disease, however increasing numbers of asymptomatic individuals are being identified. The disease is rare in the general population but is strongly associated with inflammatory bowel disease (IBD) affecting up to 5% of patients with Ulcerative Colitis, with a slightly lower prevalence (up to 3.6%) in Crohn's disease. The strength of this association means that the vast majority (> 90%) of patients with PSC also have IBD, although many may have only mild gastro-intestinal symptoms. Usually IBD presents before PSC, although vice-versa can occur and the onset of both conditions can be separated in some cases by many years. Mean age of diagnosis of PSC is in the fifth decade of life with a strong male predominance. Risk is increased in those with a family history of PSC, suggesting a genetic predisposition and the disease is almost exclusive to non-smokers. The ulcerative colitis associated with PSC is characteristically mild, runs a quiescent course, is associated with rectal sparing, more severe right sided disease, backwash ileitis and has a high risk of pouchitis post-colectomy. Most worrisome is the high risk of colorectal malignancy which necessitates routine colonoscopic surveillance. Cholangiocarcinoma is also a frequent complication of PSC with a 10%-15% lifetime risk of developing this condition. Treatment with high dose ursodeoxycholic acid offers some chemoprotective effects against colorectal malignancy and may decrease symptoms, biochemical and histological progression of liver disease. Small duct PSC patients characteristically have normal cholangiography, and liver biopsy is required for diagnosis, it appears to have a more favourable prognosis. Autoimmune Hepatitis (AIH) is also more prevalent

  14. Neither Classical nor Alternative Macrophage Activation Is Required for Pneumocystis Clearance during Immune Reconstitution Inflammatory Syndrome

    PubMed Central

    Zhang, Zhuo-Qian; Wang, Jing; Hoy, Zachary; Keegan, Achsah; Bhagwat, Samir; Gigliotti, Francis

    2015-01-01

    Pneumocystis is a respiratory fungal pathogen that causes pneumonia (Pneumocystis pneumonia [PcP]) in immunocompromised patients. Alveolar macrophages are critical effectors for CD4+ T cell-dependent clearance of Pneumocystis, and previous studies found that alternative macrophage activation accelerates fungal clearance during PcP-related immune reconstitution inflammatory syndrome (IRIS). However, the requirement for either classically or alternatively activated macrophages for Pneumocystis clearance has not been determined. Therefore, RAG2−/− mice lacking either the interferon gamma (IFN-γ) receptor (IFN-γR) or interleukin 4 receptor alpha (IL-4Rα) were infected with Pneumocystis. These mice were then immune reconstituted with wild-type lymphocytes to preserve the normal T helper response while preventing downstream effects of Th1 or Th2 effector cytokines on macrophage polarization. As expected, RAG2−/− mice developed severe disease but effectively cleared Pneumocystis and resolved IRIS. Neither RAG/IFN-γR−/− nor RAG/IL-4Rα−/− mice displayed impaired Pneumocystis clearance. However, RAG/IFN-γR−/− mice developed a dysregulated immune response, with exacerbated IRIS and greater pulmonary function deficits than those in RAG2 and RAG/IL-4Rα−/− mice. RAG/IFN-γR−/− mice had elevated numbers of lung CD4+ T cells, neutrophils, eosinophils, and NK cells but severely depressed numbers of lung CD8+ T suppressor cells. Impaired lung CD8+ T cell responses in RAG/IFN-γR−/− mice were associated with elevated lung IFN-γ levels, and neutralization of IFN-γ restored the CD8 response. These data demonstrate that restricting the ability of macrophages to polarize in response to Th1 or Th2 cytokines does not impair Pneumocystis clearance. However, a cell type-specific IFN-γ/IFN-γR-dependent mechanism regulates CD8+ T suppressor cell recruitment, limits immunopathogenesis, preserves lung function, and enhances the resolution of Pc

  15. Polyphenols rich fraction from Geoffroea decorticans fruits flour affects key enzymes involved in metabolic syndrome, oxidative stress and inflammatory process.

    PubMed

    Costamagna, M S; Zampini, I C; Alberto, M R; Cuello, S; Torres, S; Pérez, J; Quispe, C; Schmeda-Hirschmann, G; Isla, M I

    2016-01-01

    Geoffroea decorticans (chañar), is widely distributed throughout Northwestern Argentina. Its fruit is consumed as flour, arrope or hydroalcoholic beverage. The chañar fruits flour was obtained and 39 phenolic compounds were tentatively identified by HPLC-MS/MS(n). The compounds comprised caffeic acid glycosides, simple phenolics (protocatechuic acid and vanillic acid), a glycoside of vanillic acid, p-coumaric acid and its phenethyl ester as well as free and glycosylated flavonoids. The polyphenols enriched extract with and without gastroduodenal digestion inhibited enzymes associated with metabolic syndrome, including α-amylase, α-glucosidase, lipase and hydroxyl methyl glutaryl CoA reductase. The polyphenolic extract exhibited antioxidant activity by different mechanisms and inhibited the pro-inflammatory enzymes (ciclooxygenase, lipoxygenase and phospholipase A2). The polyphenolic extract did not showed mutagenic effect by Ames test against Salmonella typhimurium TA98 and TA100 strains. These findings add evidence that chañar fruit flour may be considered a functional food with preventive properties against diseases associated with oxidative stress, inflammatory mediators and metabolic syndrome. PMID:26212988

  16. Expression of pro-inflammatory TACE-TNF-α-amphiregulin axis in Sjögren's syndrome salivary glands.

    PubMed

    Sisto, Margherita; Lisi, Sabrina; Lofrumento, Dario Domenico; Ingravallo, Giuseppe; Mitolo, Vincenzo; D'Amore, Massimo

    2010-10-01

    The tumor-necrosis-factor-converting-enzyme (TACE)-TNF-α-Amphiregulin (AREG) axis plays an important pathogenic role in inflammatory and autoimmune disorders. However, the pathological roles of these proteins in the chronic autoimmune disease Sjögren's syndrome (SS) remain to be elucidated. It is known that the TACE-AREG axis is clearly part of a larger cascade of signals that starts with the activation of Furin, responsible for maturation of TACE that, in turn, determines the production of active TNF-α, directly involved in the up-regulation of AREG expression. This study showed that Furin, TACE, TNF-α, and AREG proteins, detected in acinar and ductal cells of human salivary glands from SS patients, increased remarkably in comparison with biopsies of labial salivary glands from healthy controls. The changes in Furin, TACE, TNF- α, and AREG proteins' level detected in salivary glands biopsies of SS patients could be responsible for pro-inflammatory cytokines overexpression characterizing Sjögren's syndrome.

  17. Systemic inflammatory mediators in post-traumatic Complex Regional Pain Syndrome (CRPS I) - longitudinal investigations and differences to control groups

    PubMed Central

    2009-01-01

    Objectives The Complex Regional Pain Syndrome I (CRPS I) is a disease that might affect an extremity after trauma or operation. The pathogenesis remains yet unclear. It has clinical signs of severe local inflammation as a result of an exaggerated inflammatory response but neurogenic dysregulation also contributes to it. Some studies investigated the role inflammatory mediators and cytokines; however, few longitudinal studies exist and control groups except healthy controls were not investigated yet. Methods To get further insights into the role of systemic inflammatory mediators in CRPS I, we investigated a variety of pro-, anti-, or neuro-inflammatory mediators such as C-Reactive Protein (CRP), White Blood Cell Count (WBC), Interleukins 4, 6, 8, 10, 11, 12 (p70), Interferon gamma, Tumor-Necrosis-Factor alpha (TNF-α) and its soluble Receptors I/II, soluble Selectins (E, L, P), Substance-P (SP), and Calcitonin Gene-Related Peptide (CGRP) at different time points in venous blood from patients with acute (AC) and chronic (CC) CRPS I, patients with forearm fractures (FR), with neuralgia (NE), and from healthy volunteers (C). Results No significant changes for serum parameters investigated in CRPS compared to control groups were found except for CC/C (CGRP p = 0.007), FR/C (CGRP p = 0.048) and AC/CC (IL-12 p = 0.02; TNFRI/II p = 0.01; SP p = 0.049). High interindividual variations were observed. No intra-or interindividual correlation of parameters with clinical course (e.g. chronification) or outcome was detectable. Conclusion Although clinically appearing as inflammation in acute stages, local rather than systemic inflammatory responses seem to be relevant in CRPS. Variable results from different studies might be explained by unpredictable intermittent release of mediators from local inflammatory processes into the blood combined with high interindividual variabilities. A clinically relevant difference to various control groups was not notable in this pilot study

  18. The Role of Dietary Inflammatory Index in Cardiovascular Disease, Metabolic Syndrome and Mortality

    PubMed Central

    Ruiz-Canela, Miguel; Bes-Rastrollo, Maira; Martínez-González, Miguel A.

    2016-01-01

    Inflammation is an underlying pathophysiological process in chronic diseases, such as obesity, type 2 diabetes mellitus and cardiovascular disease. In fact, a number of systematic reviews have shown the association between inflammatory biomarkers, such as CRP, IL-1β, IL-6, TNF-α, IL-4, or IL-10, and cardio-metabolic diseases. Diet is one of the main lifestyle-related factors which modulates the inflammatory process. Different individual foods and dietary patterns can have a beneficial health effect associated with their anti-inflammatory properties. The dietary inflammatory index (DII) was recently developed to estimate the inflammatory potential of overall diet. The aim of this review is to examine the findings of recent papers that have investigated the association between the DII, cardio-metabolic risk factors and cardiovascular disease. The relevance of the DII score in the association between inflammation and cardio-metabolic diseases is critically appraised, as well as its role in the context of healthy dietary patterns. We conclude that the DII score seems to be a useful tool to appraise the inflammatory capacity of the diet and to better understand the relationships between diet, inflammation, and cardio-metabolic diseases. PMID:27527152

  19. The Role of Dietary Inflammatory Index in Cardiovascular Disease, Metabolic Syndrome and Mortality.

    PubMed

    Ruiz-Canela, Miguel; Bes-Rastrollo, Maira; Martínez-González, Miguel A

    2016-08-03

    Inflammation is an underlying pathophysiological process in chronic diseases, such as obesity, type 2 diabetes mellitus and cardiovascular disease. In fact, a number of systematic reviews have shown the association between inflammatory biomarkers, such as CRP, IL-1β, IL-6, TNF-α, IL-4, or IL-10, and cardio-metabolic diseases. Diet is one of the main lifestyle-related factors which modulates the inflammatory process. Different individual foods and dietary patterns can have a beneficial health effect associated with their anti-inflammatory properties. The dietary inflammatory index (DII) was recently developed to estimate the inflammatory potential of overall diet. The aim of this review is to examine the findings of recent papers that have investigated the association between the DII, cardio-metabolic risk factors and cardiovascular disease. The relevance of the DII score in the association between inflammation and cardio-metabolic diseases is critically appraised, as well as its role in the context of healthy dietary patterns. We conclude that the DII score seems to be a useful tool to appraise the inflammatory capacity of the diet and to better understand the relationships between diet, inflammation, and cardio-metabolic diseases.

  20. The Role of Dietary Inflammatory Index in Cardiovascular Disease, Metabolic Syndrome and Mortality.

    PubMed

    Ruiz-Canela, Miguel; Bes-Rastrollo, Maira; Martínez-González, Miguel A

    2016-01-01

    Inflammation is an underlying pathophysiological process in chronic diseases, such as obesity, type 2 diabetes mellitus and cardiovascular disease. In fact, a number of systematic reviews have shown the association between inflammatory biomarkers, such as CRP, IL-1β, IL-6, TNF-α, IL-4, or IL-10, and cardio-metabolic diseases. Diet is one of the main lifestyle-related factors which modulates the inflammatory process. Different individual foods and dietary patterns can have a beneficial health effect associated with their anti-inflammatory properties. The dietary inflammatory index (DII) was recently developed to estimate the inflammatory potential of overall diet. The aim of this review is to examine the findings of recent papers that have investigated the association between the DII, cardio-metabolic risk factors and cardiovascular disease. The relevance of the DII score in the association between inflammation and cardio-metabolic diseases is critically appraised, as well as its role in the context of healthy dietary patterns. We conclude that the DII score seems to be a useful tool to appraise the inflammatory capacity of the diet and to better understand the relationships between diet, inflammation, and cardio-metabolic diseases. PMID:27527152

  1. Effect of Sepsis and Systemic Inflammatory Response Syndrome on Neonatal Hearing Screening Outcomes following Gentamicin Exposure

    PubMed Central

    Cross, Campbell P.; Liao, Selena; Urdang, Zachary D.; Srikanth, Priya; Garinis, Angela C.; Steyger, Peter S.

    2015-01-01

    Rationale Hearing loss in neonatal intensive care unit (NICU) graduates range from 2–15% compared to 0.3% in full-term births, and the etiology of this discrepancy remains unknown. The majority of NICU admissions receive potentially ototoxic aminoglycoside therapy, such as gentamicin, for presumed sepsis. Endotoxemia and inflammation are associated with increased cochlear uptake of aminoglycosides and potentiated ototoxicity in mice. We tested the hypothesis that sepsis or systemic inflammatory response syndrome (SIRS) and intravenous gentamicin exposure increases the risk of hearing loss in NICU admissions. Methods The Institutional Review Board at Oregon Health & Science University (OHSU) approved this study design. Two hundred and eight infants met initial criteria, and written, informed consent were obtained from parents or guardians of 103 subjects ultimately enrolled in this study. Prospective data from 91 of the enrolled subjects at OHSU Doernbecher Children’s Hospital Neonatal Care Center were processed. Distortion product otoacoustic emissions (DPOAEs; f2 frequency range: 2,063 to 10,031 Hz) were obtained prior to discharge to assess auditory performance. To pass the DPOAE screen, normal responses in >6 of 10 frequencies in both ears were required; otherwise the subject was considered a “referral” for a diagnostic hearing evaluation after discharge. Cumulative dosing data and diagnosis of neonatal sepsis or SIRS were obtained from OHSU’s electronic health record system, and the data processed to obtain risk ratios. Results Using these DPOAE screening criteria, 36 (39.5%) subjects would be referred. Seventy-four (81%) subjects had intravenous gentamicin exposure. Twenty (22%) had ≥4 days of gentamicin, and 71 (78%) had <4 days. The risk ratio (RR) of referral with ≥4 days of gentamicin was 1.92 (p=0.01). Eighteen subjects had sepsis or met neonatal SIRS criteria, 9 of whom had ≥5 days of gentamicin and a DPOAE referral risk ratio of 2.12 (p

  2. Inflammatory responses to neutral fat and fatty acids in multiple organs in a rat model of fat embolism syndrome.

    PubMed

    Takada, Meri; Chiba, Shoetsu; Nagai, Tomonori; Takeshita, Hiroshi; Kanno, Sanae; Ikawa, Toru; Sakamoto, Kana; Sagi, Morihisa; Ichiba, Kazue; Mukai, Toshiji

    2015-09-01

    Fat embolism syndrome (FES) is a common complication of long bone fractures. FES is rare but with significant morbidity and occasional fatalities. Studies of animal models of FES are numerous; however, few studies compare inflammatory reactions in multiple organs. The present study investigated the effect of neutral fat and fatty acids, which cause changes in multiple organs and induce FES. Using rats we evaluated the ratio of lung-to-body weight and conducted histological analyses and quantitative analysis of inflammatory cytokine mRNAs in the lungs following intravenous administration of neutral fat or fatty acids. Neutral fat increased the ratio of lung-to-body weight, and neutral fat formed emboli in lung capillaries. The levels of interleukin-1 beta (IL-1β), IL-6 and tumor necrosis factor-alpha (TNF-α) in the lungs increased after injection of neutral fat and oleic acid. Analysis of the histologic changes revealed that the highest numbers of fat droplets, occluding the capillaries of the lungs, kidney, heart, and brain formed 12h after the injection of neutral fat and fat droplets gradually diminished 48h later. Fat droplets were not detected in any organs after the injection of oleic acid. IL-1β and TNF-α levels in the lungs were elevated 9-24h after the injection of neutral fat, although IL-6 levels peaked at 6h. After injection of oleic acid, peak levels of IL-1β, IL-6, and TNF-α were detected at 6h, and IL-6 again increased in all organs and plasma at 15h. Neutral fat, but not fatty acids, formed emboli in the capillaries of multiple organs. These findings suggest that neutral fat increased inflammatory cytokine levels by forming emboli in organ capillaries, particularly in the lungs, while oleic acid augmented inflammatory cytokine levels by stimulating endothelial cells of multiple organs.

  3. Ulcerating type 1 lepra reaction mimicking lazarine leprosy: an unusual presentation of immune reconstitution inflammatory syndrome in an HIV-infected patient.

    PubMed

    Bhat, Ramesh; Pinto, Malcolm; Dandakeri, Sukumar; Kambil, Srinath

    2013-12-01

    Leprosy maybe "unmasked" in the context of immune reconstitution inflammatory syndrome and treating dermatologists, particularly in highly endemic areas for Hansen's disease, need to be cognizant to this possibility. It may also reflect emergence of a previously clinically silent infection in the course of immunologic restoration. PMID:24216029

  4. Genetics of Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP): current knowledge and future directions.

    PubMed

    Blum, Stefan; McCombe, Pamela A

    2014-06-01

    Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) are thought to be autoimmune diseases. There have been many attempts to find a human leukocyte antigen (HLA) association with GBS and CIDP with little success. There have been studies of other plausible genes in GBS and CIDP and the role of these genes in GBS and CIDP and the data from these genetic studies is reviewed. Some of the genes that have been studied are immune related and some others have nervous system effects. The studies are limited by small numbers. Some of the genes show association with disease severity rather than disease susceptibility. The need for more detailed molecular studies of the role of HLA molecules and the need for modern genetic approaches to GBS and CIDP are explained.

  5. Amelioration of Acute Kidney Injury in Lipopolysaccharide-Induced Systemic Inflammatory Response Syndrome by an Aldose Reductase Inhibitor, Fidarestat

    PubMed Central

    Takahashi, Kazunori; Mizukami, Hiroki; Kamata, Kosuke; Inaba, Wataru; Kato, Noriaki; Hibi, Chihiro; Yagihashi, Soroku

    2012-01-01

    Background Systemic inflammatory response syndrome is a fatal disease because of multiple organ failure. Acute kidney injury is a serious complication of systemic inflammatory response syndrome and its genesis is still unclear posing a difficulty for an effective treatment. Aldose reductase (AR) inhibitor is recently found to suppress lipopolysaccharide (LPS)-induced cardiac failure and its lethality. We studied the effects of AR inhibitor on LPS-induced acute kidney injury and its mechanism. Methods Mice were injected with LPS and the effects of AR inhibitor (Fidarestat 32 mg/kg) before or after LPS injection were examined for the mortality, severity of renal failure and kidney pathology. Serum concentrations of cytokines (interleukin-1β, interleukin-6, monocyte chemotactic protein-1 and tumor necrosis factor-α) and their mRNA expressions in the lung, liver, spleen and kidney were measured. We also evaluated polyol metabolites in the kidney. Results Mortality rate within 72 hours was significantly less in LPS-injected mice treated with AR inhibitor both before (29%) and after LPS injection (40%) than untreated mice (90%). LPS-injected mice showed marked increases in blood urea nitrogen, creatinine and cytokines, and AR inhibitor treatment suppressed the changes. LPS-induced acute kidney injury was associated with vacuolar degeneration and apoptosis of renal tubular cells as well as infiltration of neutrophils and macrophages. With improvement of such pathological findings, AR inhibitor treatment suppressed the elevation of cytokine mRNA levels in multiple organs and renal sorbitol accumulation. Conclusion AR inhibitor treatment ameliorated LPS-induced acute kidney injury, resulting in the lowered mortality. PMID:22253906

  6. Inflammatory Cytokine Profile Associated with Metabolic Syndrome in Adult Patients with Type 1 Diabetes

    PubMed Central

    Ferreira-Hermosillo, Aldo; Molina-Ayala, Mario; Ramírez-Rentería, Claudia; Vargas, Guadalupe; Gonzalez, Baldomero; Isibasi, Armando; Archundia-Riveros, Irma; Mendoza, Victoria

    2015-01-01

    Objective. To compare the serum concentration of IL-6, IL-10, TNF, IL-8, resistin, and adiponectin in type 1 diabetic patients with and without metabolic syndrome and to determine the cut-off point of the estimated glucose disposal rate that accurately differentiated these groups. Design. We conducted a cross-sectional evaluation of all patients in our type 1 diabetes clinic from January 2012 to January 2013. Patients were considered to have metabolic syndrome when they fulfilled the joint statement criteria and were evaluated for clinical, biochemical, and immunological features. Methods. We determined serum IL-6, IL-8, IL-10, and TNF with flow cytometry and adiponectin and resistin concentrations with enzyme linked immunosorbent assay in patients with and without metabolic syndrome. We also compared estimated glucose disposal rate between groups. Results. We tested 140 patients. Forty-four percent fulfilled the metabolic syndrome criteria (n = 61), 54% had central obesity, 30% had hypertriglyceridemia, 29% had hypoalphalipoproteinemia, and 19% had hypertension. We observed that resistin concentrations were higher in patients with MS. Conclusion. We found a high prevalence of MS in Mexican patients with T1D. The increased level of resistin may be related to the increased fat mass and could be involved in the development of insulin resistance. PMID:26273680

  7. Associations among gut permeability, inflammatory markers, and symptoms in patients with irritable bowel syndrome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Alterations in gastrointestinal (GI) permeability and immune measures are present in some patients with irritable bowel syndrome (IBS) but the relationship to symptoms is poorly defined. In adults with IBS, we compared permeability, unstimulated peripheral blood monocyte (PBMC) interleukin-10 (IL-10...

  8. Contribution of Blastocystishominis subtypes and associated inflammatory factors in development of irritable bowel syndrome.

    PubMed

    Azizian, Marzieh; Basati, Gholam; Abangah, Ghobad; Mahmoudi, Mohammad Reza; Mirzaei, Asad

    2016-05-01

    Blastocystis hominis with worldwide distribution is a human intestinal protozoa found in all countries. There have been differences in the severity of the pathogenesis of various Blastocystis spp. and a concomitant variation in the plasma concentration of the cytokines in patients with irritable bowel syndrome. In the present study, we aimed to demonstrate the contribution of B. hominis subtypes in the development of irritable bowel syndrome. Stool samples were collected from patients with gastrointestinal disorders. All samples were evaluated through native-lugol method. Total DNA was extracted. A PCR protocol was developed to amplify a specific region of the SSU ribosomal DNA (rDNA) gene. Serum levels of IL-6 and TNF-α were determined by immunoassay methods. The ClustalW algorithm was applied to align and blast the nucleotide sequences of the amplified region of the SSU rDNA gene. To evaluate the phylogenetic and molecular evolutionary of the nucleotide sequences, we used the MEGA software. In this study, we found 26 haplotypes of B. hominis in the studied samples which were collectively belong to five subtypes (ST1, ST2 in patients without irritable bowel syndrome vs. ST3 and two unknown subtypes in patients with irritable bowel syndrome). Result of ELISA showed a high level of IL-6 and TNF-α in the serum of patients with irritable bowel syndrome. The genetic heterogeneity of B. hominis and the existence of different subtypes of the protozoan in patients with IBS may shed light to the fact that some subtypes of parasites may involve in the pathogenesis of IBS. PMID:26841770

  9. Immunohistochemical expression of MPO, CD163 and VEGF in inflammatory cells in acute respiratory distress syndrome: a case report

    PubMed Central

    Maretta, Milan; Toth, Stefan; Jonecova, Zuzana; Kruzliak, Peter; Kubatka, Peter; Pingorova, Stanislava; Vesela, Jarmila

    2014-01-01

    Acute respiratory distress syndrome (ARDS) is a serious medical condition occurring in patients with polytrauma, pulmonary or non-pulmonary sepsis, pneumonia and many other circumstances. It causes inflammation of the lung parenchyma leading to impaired gas exchange with a systemic release of inflammatory mediators, causing consequential lung tissue injury, hypoxemia and frequently multiple organ failure. The aim of current study was to describe expression of inflammatory markers (myeloperoxidase, CD163 and vascular endothelial growth factor) by the cells in acute phase of ARDS. The lung samples of a 20-year-old man who had suffered a serious motorbike accident were obtained for histological examination. He died on the seventh day as a consequence of respiratory failure. Our results imply that expression of CD163 was restricted to activated alveolar macrophages and monocytes. Immunopositivityof MPO was observed in neutrophil granulocytes within lung alveoli and lung blood vessels. Myeloperoxidase positivity was observed in alveolar macrophages, too. Vascular endothelial growth factor was expressed in cytoplasm of neutrophil granulocytes, monocytes, small-sized alveolar macrophages and type II pneumocytes localized mostly inside lung alveoli. On the contrary, no positivity was observed in lung endothelial cells of blood vessels. PMID:25120850

  10. Latest Study on the Relationship between Pathological Process of Inflammatory Injury and the Syndrome of Spleen Deficiency and Fluid Retention in Alzheimer's Disease

    PubMed Central

    Yu, Beibei; Zhou, Chunxiang; Zhang, Jiangyuan; Ling, Yun; Hu, Qianfeng; Wang, Yi; Bai, Kangkang

    2014-01-01

    Inflammation exists throughout the incidence and progression of Alzheimer's disease (AD). Traditional Chinese medicine (TCM) differentiates the pathogenesis of AD as kidney essence deficiency and qi and blood deficiency as well as blood stasis in syndromes, whose action mechanisms are all associated with the intervention in its inflammatory process. Our preliminary studies both in clinic and in vitro have demonstrated that the syndrome of spleen deficiency and fluid retention has also been an important pathogenesis for the incidence and development of AD. Hence, the paper aims to further illustrate the correlation between inflammatory process in AD and the syndrome of spleen deficiency and fluid retention, laying solid foundation for the application of invigorating the spleen and eliminating the dampness in clinic, and enriching the theoretical connotation for AD prevention and treatment in TCM. PMID:24799943

  11. Effects of Bread with Nigella Sativa on Lipid Profiles, Apolipoproteins and Inflammatory Factor in Metabolic Syndrome Patients.

    PubMed

    Mohtashami, Alireaz; Mahaki, Behzad; Azadbakht, Leila; Entezari, Mohammad Hasan

    2016-04-01

    Nigella sativa (N.sativa) has been used in traditional medicine and many studies have been performed in different communities in order to reveal the effects of it on medical disorders and chronic diseases. The aim of this study was to investigate the effects of bread with N. Sativa on lipid profiles, apolipoproteins, and inflammatory factors in metabolic syndrome (MetS) patients. A randomized, double-blind, cross-over and clinical trial was conducted in 51 MetS patients of both sexes with age group of 20-65 years old in Chaloos, north of Iran. Patients were randomly divided in two groups. In phase 1, intervention group (A, n = 27) received daily a bread with N. sativa and wheat bran and control group (B, n = 24) received the same bread without N. sativa for 2 months. After 2 weeks of wash out period, phase 2 was started with switch the intervention between two groups. Measuring of lipid profiles, apolipoproteins and inflammatory factor was performed for all patients before and after two phases. In this study, treatment, sequence and time effects of intervention were evaluated and revealed that consumption of bread with N. sativa has no significant treatment and time effects on triglyceride (TG), cholesterol (CHOL), low density lipoprotein (LDL), high density lipoprotein (HDL), apolipoprotein (APO)-A, APO-B and high-sensitivity C-reactive protein (p > 0.05). Sequence effect was significant on CHOL, LDL, APO-A, and APO-B (p < 0.05) but was not significant on other parameters (p > 0.05). Consumption of bread with N. sativa has no a significant effect on lipid profiles, apolipoproteins and inflammatory factor in MetS patients.

  12. Effects of Bread with Nigella Sativa on Lipid Profiles, Apolipoproteins and Inflammatory Factor in Metabolic Syndrome Patients

    PubMed Central

    2016-01-01

    Nigella sativa (N.sativa) has been used in traditional medicine and many studies have been performed in different communities in order to reveal the effects of it on medical disorders and chronic diseases. The aim of this study was to investigate the effects of bread with N. Sativa on lipid profiles, apolipoproteins, and inflammatory factors in metabolic syndrome (MetS) patients. A randomized, double-blind, cross-over and clinical trial was conducted in 51 MetS patients of both sexes with age group of 20-65 years old in Chaloos, north of Iran. Patients were randomly divided in two groups. In phase 1, intervention group (A, n = 27) received daily a bread with N. sativa and wheat bran and control group (B, n = 24) received the same bread without N. sativa for 2 months. After 2 weeks of wash out period, phase 2 was started with switch the intervention between two groups. Measuring of lipid profiles, apolipoproteins and inflammatory factor was performed for all patients before and after two phases. In this study, treatment, sequence and time effects of intervention were evaluated and revealed that consumption of bread with N. sativa has no significant treatment and time effects on triglyceride (TG), cholesterol (CHOL), low density lipoprotein (LDL), high density lipoprotein (HDL), apolipoprotein (APO)-A, APO-B and high-sensitivity C-reactive protein (p > 0.05). Sequence effect was significant on CHOL, LDL, APO-A, and APO-B (p < 0.05) but was not significant on other parameters (p > 0.05). Consumption of bread with N. sativa has no a significant effect on lipid profiles, apolipoproteins and inflammatory factor in MetS patients. PMID:27152298

  13. Effects of Bread with Nigella Sativa on Lipid Profiles, Apolipoproteins and Inflammatory Factor in Metabolic Syndrome Patients.

    PubMed

    Mohtashami, Alireaz; Mahaki, Behzad; Azadbakht, Leila; Entezari, Mohammad Hasan

    2016-04-01

    Nigella sativa (N.sativa) has been used in traditional medicine and many studies have been performed in different communities in order to reveal the effects of it on medical disorders and chronic diseases. The aim of this study was to investigate the effects of bread with N. Sativa on lipid profiles, apolipoproteins, and inflammatory factors in metabolic syndrome (MetS) patients. A randomized, double-blind, cross-over and clinical trial was conducted in 51 MetS patients of both sexes with age group of 20-65 years old in Chaloos, north of Iran. Patients were randomly divided in two groups. In phase 1, intervention group (A, n = 27) received daily a bread with N. sativa and wheat bran and control group (B, n = 24) received the same bread without N. sativa for 2 months. After 2 weeks of wash out period, phase 2 was started with switch the intervention between two groups. Measuring of lipid profiles, apolipoproteins and inflammatory factor was performed for all patients before and after two phases. In this study, treatment, sequence and time effects of intervention were evaluated and revealed that consumption of bread with N. sativa has no significant treatment and time effects on triglyceride (TG), cholesterol (CHOL), low density lipoprotein (LDL), high density lipoprotein (HDL), apolipoprotein (APO)-A, APO-B and high-sensitivity C-reactive protein (p > 0.05). Sequence effect was significant on CHOL, LDL, APO-A, and APO-B (p < 0.05) but was not significant on other parameters (p > 0.05). Consumption of bread with N. sativa has no a significant effect on lipid profiles, apolipoproteins and inflammatory factor in MetS patients. PMID:27152298

  14. Discovery of potential new gene variants and inflammatory cytokine associations with fibromyalgia syndrome by whole exome sequencing.

    PubMed

    Feng, Jinong; Zhang, Zhifang; Wu, Xiwei; Mao, Allen; Chang, Frances; Deng, Xutao; Gao, Harry; Ouyang, Ching; Dery, Kenneth J; Le, Keith; Longmate, Jeffrey; Marek, Claudia; St Amand, R Paul; Krontiris, Theodore G; Shively, John E

    2013-01-01

    Fibromyalgia syndrome (FMS) is a chronic musculoskeletal pain disorder affecting 2% to 5% of the general population. Both genetic and environmental factors may be involved. To ascertain in an unbiased manner which genes play a role in the disorder, we performed complete exome sequencing on a subset of FMS patients. Out of 150 nuclear families (trios) DNA from 19 probands was subjected to complete exome sequencing. Since >80,000 SNPs were found per proband, the data were further filtered, including analysis of those with stop codons, a rare frequency (<2.5%) in the 1000 Genomes database, and presence in at least 2/19 probands sequenced. Two nonsense mutations, W32X in C11orf40 and Q100X in ZNF77 among 150 FMS trios had a significantly elevated frequency of transmission to affected probands (p = 0.026 and p = 0.032, respectively) and were present in a subset of 13% and 11% of FMS patients, respectively. Among 9 patients bearing more than one of the variants we have described, 4 had onset of symptoms between the ages of 10 and 18. The subset with the C11orf40 mutation had elevated plasma levels of the inflammatory cytokines, MCP-1 and IP-10, compared with unaffected controls or FMS patients with the wild-type allele. Similarly, patients with the ZNF77 mutation have elevated levels of the inflammatory cytokine, IL-12, compared with controls or patients with the wild type allele. Our results strongly implicate an inflammatory basis for FMS, as well as specific cytokine dysregulation, in at least 35% of our FMS cohort.

  15. Anti-inflammatory effect of amlodipine plus atorvastatin treatment on carotid atherosclerosis in zucker metabolic syndrome rats.

    PubMed

    Zhang, Xuemei; Tian, Fengfeng; Kawai, Hiromi; Kurata, Tomoko; Deguchi, Shoko; Deguchi, Kentaro; Shang, Jingwei; Liu, Ning; Liu, Wentao; Ikeda, Yoshio; Matsuura, Tohru; Kamiya, Tatsushi; Abe, Koji

    2012-12-01

    To investigate the effects of amlodipine in combination with atorvastatin on carotid atherosclerotic changes in metabolic syndrome, 8-week-old Zucker fatty rats were treated with vehicle, amlodipine, atorvastatin, or amlodipine in combination with atorvastatin for 28 days. Histological studies of common carotid arteries showed that lipid deposition determined by Sudan III staining was significantly reduced in rats treated with amlodipine or atorvastatin alone and was further reduced by amlodipine in combination with atorvastatin. Immunohistochemical studies of the pro-inflammatory cytokine tumor necrosis factor (TNF)-α, the arterial calcification initiator bone morphogenetic protein (BMP) 2, the angiogenic factor Notch1, and the smooth muscle cell marker α-smooth muscle actin (SMA) showed that the high expression of all four protein in vehicle-treated rats was greatly decreased by amlodipine, atorvastatin, or amlodipine in combination with atorvastatin, in ascending order. Double immunostaining showed marked colocalization of TNF-α with bone morphogenetic protein 2 and Notch1 with α-SMA in the vehicle group, which was greatly reduced by amlodipine plus atorvastatin. These data suggest that combination therapy may be more effective in preventing atherosclerotic processes and subsequent carotid vascular events than administrating amlodipine or atorvastatin alone in metabolic syndrome. PMID:24323832

  16. Effects of Acupuncture Knife on Inflammatory Factors and Pain in Third Lumbar Vertebrae Transverse Process Syndrome Model Rats

    PubMed Central

    Yu, Jia Ni; Guo, Chang Qing; Hu, Bo; Liu, Nai Gang; Sun, Hong Mei; Xu, Hong; Wu, Hai Xia; Guo, Yan; Liang, Chu Xi; Chen, Zhan Xia; Li, Xiao Hong

    2014-01-01

    The aim of this paper was to explore the long-term effects and pain relief mechanism of acupuncture knife on third lumbar vertebrae (L3) transverse process syndrome. Forty SD rats were randomized into control, model, electroacupuncture (EA), and acupuncture knife (AK) group. Except control rats, other rats were subjected to an operation to emulate L3 transverse process syndrome. Fourteen days after the operation, EA and AK rats were given electroacupuncture and acupuncture knife treatments, respectively. Fifty-six days after the operation, enzyme-linked immunosorbent assay was used to measure substance P (SP), 5-hydroxytryptamine (5-HT), interleukin-1β (IL-1β), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), and transforming growth factor-β (TGF-β) in peripheral blood. The tail flick test was used to observe pain threshold. We found that rats with the simulation operation had significantly higher levels of SP, 5-HT, IL-1, IL-10, TNF-α, and TGF-β, while the AK rats had lower levels. In addition, the pain threshold of AK rats was similar to that of control rats. AK pretreatment could alleviate pain through modulating inflammatory response. PMID:25544854

  17. Inflammatory myofibroblastic bladder tumor in a patient with wolf-hirschhorn syndrome.

    PubMed

    Marte, Antonio; Indolfi, Paolo; Ficociello, Carmine; Russo, Daniela; Oreste, Matilde; Bottigliero, Gaetano; Gualdiero, Giovanna; Barone, Ciro; Vigliar, Elena; Indolfi, Cristiana; Casale, Fiorina

    2013-01-01

    Inflammatory myofibroblastic tumor (IMT) is a rare neoplasm described in several tissues and organs including genitourinary system, lung, head, and neck. The etiology of IMT is contentious, and whether it is a postinflammatory process or a true neoplasm remains controversial. To our knowledge, we report the first reported case of IMT of urinary bladder in a pediatric patient with Wolf-Hirschhorn (WHS). We also review the literature about patients with associated neoplasia. PMID:24024066

  18. Inflammatory myopathy and interstitial lung disease in antisynthetase syndrome with PL-7 antibody

    PubMed Central

    Aguiar Rosa, Sílvia; Barreto, Paulo; Mariano, Marisa; Baptista, Isabel

    2014-01-01

    We report a case of a 72-year-old Caucasian woman with PL-7 positive antisynthetase syndrome. Clinical presentation included interstitial lung disease, myositis, ‘mechanic's hands’ and dysphagia. As lung injury was the main concern, treatment consisted of prednisolone and cyclophosphamide. Complete remission with reversal of pulmonary damage was achieved, as reported by CT scan, pulmonary function tests and functional status. PMID:25293682

  19. Pro-inflammatory chemokine C-C motif ligand 16 (CCL-16) dysregulation in irritable bowel syndrome (IBS): a pilot study

    PubMed Central

    DEL VALLE-PINERO, A. Y.; MARTINO, A. C.; TAYLOR, T. J.; MAJORS, B. L.; PATEL, N. S.; HEITKEMPER, M. M.; HENDERSON, W. A.

    2012-01-01

    Background Irritable bowel syndrome (IBS) is a serious health problem that affects an estimated 10–15% of people worldwide and has economic consequences in the United States of over $30 billion annually. In the US, IBS affects all races and both sexes, with more females than males (2 : 1) reporting symptoms consistent with IBS. Although the etiology of this functional gastrointestinal disorder is unknown, literature suggests that a subclinical inflammatory component has a role in the etiologic mechanisms underlying IBS. The aim of this study was to evaluate the gene expression of inflammatory biomarkers in patients with and without IBS and among different IBS phenotypes. Methods Irritable bowel syndrome patients (n = 12) that met Rome III Criteria for IBS longer than 6 months were compared with healthy matched controls (n = 12). Peripheral whole blood from fasting participants was collected and RNA was extracted. The expression of 96 inflammatory genes was then analyzed using a custom quantitative real-time PCR array. Key Results CCL-16 gene expression was upregulated by 7.46-fold in IBS patients when compared with controls. CCL-16 was overexpressed by over 130-fold in IBS-constipation patients when compared with both controls and IBS-diarrhea patients. Conclusions & Inferences These results further suggest a subclinical inflammatory component underlying IBS. To better understand the phenotypic differences in IBS it is important to broaden the study of these inflammatory and other biomarkers. PMID:21951809

  20. Chronic fatigue syndrome and fibromyalgia following immunization with the hepatitis B vaccine: another angle of the 'autoimmune (auto-inflammatory) syndrome induced by adjuvants' (ASIA).

    PubMed

    Agmon-Levin, Nancy; Zafrir, Yaron; Kivity, Shaye; Balofsky, Ari; Amital, Howard; Shoenfeld, Yehuda

    2014-12-01

    The objectives of this study were to gather information regarding demographic and clinical characteristics of patients diagnosed with either fibromyalgia (FM) or chronic fatigue (CFS) following hepatitis B vaccination (HBVv) and furthermore to apply the recently suggested criteria of autoimmune (auto-inflammatory) syndromes induced by adjuvants (ASIA), in the aim of identifying common characteristics that may suggest an association between fibromyalgia, chronic fatigue and HBV vaccination. Medical records of 19 patients with CFS and/or fibromyalgia following HBVv immunization were analyzed. All of which were immunized during 1990-2008 in different centers in the USA. All medical records were evaluated for demographics, medical history, the number of vaccine doses, as well as immediate and long term post-immunization adverse events and clinical manifestations. In addition, available blood tests, imaging results, treatments and outcomes were analyzed. ASIA criteria were applied to all patients. The mean age of patients was 28.6 ± 11 years, of which 68.4 % were females. 21.05 % had either personal or familial background of autoimmune disease. The mean latency period from the last dose of HBVv to onset of symptoms was 38.6 ± 79.4 days, ranging from days to a year. Eight (42.1 %) patients continued with the immunization program despite experiencing adverse events. Manifestations that were commonly reported included neurological manifestations (84.2 %), musculoskeletal (78.9 %), psychiatric (63.1 %), fatigue (63.1 %), gastrointestinal complains (58 %) and mucocutaneous manifestations (36.8 %). Autoantibodies were detected in 71 % of patients tested. All patients fulfilled the ASIA criteria. This study suggests that in some cases CFS and FM can be temporally related to immunization, as part of ASIA syndrome. The appearance of adverse event during immunization, the presence of autoimmune susceptibility and higher titers of autoantibodies all can be suggested as risk

  1. Chronic fatigue syndrome and fibromyalgia following immunization with the hepatitis B vaccine: another angle of the 'autoimmune (auto-inflammatory) syndrome induced by adjuvants' (ASIA).

    PubMed

    Agmon-Levin, Nancy; Zafrir, Yaron; Kivity, Shaye; Balofsky, Ari; Amital, Howard; Shoenfeld, Yehuda

    2014-12-01

    The objectives of this study were to gather information regarding demographic and clinical characteristics of patients diagnosed with either fibromyalgia (FM) or chronic fatigue (CFS) following hepatitis B vaccination (HBVv) and furthermore to apply the recently suggested criteria of autoimmune (auto-inflammatory) syndromes induced by adjuvants (ASIA), in the aim of identifying common characteristics that may suggest an association between fibromyalgia, chronic fatigue and HBV vaccination. Medical records of 19 patients with CFS and/or fibromyalgia following HBVv immunization were analyzed. All of which were immunized during 1990-2008 in different centers in the USA. All medical records were evaluated for demographics, medical history, the number of vaccine doses, as well as immediate and long term post-immunization adverse events and clinical manifestations. In addition, available blood tests, imaging results, treatments and outcomes were analyzed. ASIA criteria were applied to all patients. The mean age of patients was 28.6 ± 11 years, of which 68.4 % were females. 21.05 % had either personal or familial background of autoimmune disease. The mean latency period from the last dose of HBVv to onset of symptoms was 38.6 ± 79.4 days, ranging from days to a year. Eight (42.1 %) patients continued with the immunization program despite experiencing adverse events. Manifestations that were commonly reported included neurological manifestations (84.2 %), musculoskeletal (78.9 %), psychiatric (63.1 %), fatigue (63.1 %), gastrointestinal complains (58 %) and mucocutaneous manifestations (36.8 %). Autoantibodies were detected in 71 % of patients tested. All patients fulfilled the ASIA criteria. This study suggests that in some cases CFS and FM can be temporally related to immunization, as part of ASIA syndrome. The appearance of adverse event during immunization, the presence of autoimmune susceptibility and higher titers of autoantibodies all can be suggested as risk

  2. Lung inflammatory response syndrome after cardiac-operations and treatment of lornoxicam

    PubMed Central

    Tsakiridis, Kosmas; Mpakas, Andreas; Kesisis, George; Arikas, Stamatis; Argyriou, Michael; Siminelakis, Stavros; Katsikogiannis, Nikolaos; Kougioumtzi, Ioanna; Tsiouda, Theodora; Sarika, Eirini; Katamoutou, Ioanna; Zarogoulidis, Konstantinos

    2014-01-01

    The majority of patients survive after extracorporeal circulation without any clinically apparent deleterious effects. However, disturbances exist in various degrees sometimes, which indicate the harmful effects of cardiopulmonary bypass (CPB) in the body. Several factors during extracorporeal circulation either mechanical dependent (exposure of blood to non-biological area) or mechanical independent (surgical wounds, ischemia and reperfusion, alteration in body temperature, release of endotoxins) have been shown to trigger the inflammatory reaction of the body. The complement activation, the release of cytokines, the leukocyte activation and accumulation as well as the production of several “mediators” such as oxygen free radicals, metabolites of arachidonic acid, platelet activating factors (PAF), nitric acid, and endothelin. The investigation continues today on the three metabolites of lornoxicam (the hydroxylated metabolite and two other metabolites of unknown chemical composition) to search for potential new pharmacological properties and activities. PMID:24672703

  3. Inflammatory myopathies and overlap syndromes: Update on histological and serological profile.

    PubMed

    Colafrancesco, Serena; Priori, Roberta; Valesini, Guido

    2015-12-01

    The term 'inflammatory myopathies' (IMs) comprise a group of muscle diseases formed by four main categories known as polymyositis (PM), dermatomyositis (DM), inclusion body myositis (IBM) and immune-mediated necrotizing myopathy (IMNM). Due to the increasing evidence of IMs over the course of different autoimmune diseases, the overlap myositis (OM) has been recently recognized as a possible stand-alone entity. IMs are characterized by a wide spectrum of autoantibodies, and the panel of myositis-associated autoantibodies (MAA) has dramatically increased over the last years giving the clinicians a further crucial support to differentiate the different types of myositis. This study aims to collect the most relevant evidence published up to date on the most commonly described OM with a particular emphasis on their histological aspects and also serological features. PMID:27107515

  4. Inflammatory and immune markers associated with physical frailty syndrome: findings from Singapore longitudinal aging studies

    PubMed Central

    Lu, Yanxia; Tan, Crystal Tze Ying; Nyunt, Ma Shwe Zin; Mok, Esther Wing Hei; Camous, Xavier; Kared, Hassen; Fulop, Tamas; Feng, Liang

    2016-01-01

    Chronic systematic inflammation and reduced immune system fitness are considered potential contributing factors to the development of age-related frailty, but the underlying mechanisms are poorly defined. This exploratory study aimed to identify frailty-related inflammatory markers and immunological phenotypes in a cohort of community-dwelling adults aged ≥ 55 years. Frailty was assessed using two models, a Frailty Index and a categorical phenotype, and correlated with levels of circulating immune biomarkers and markers of senescence in immune cell subsets. We identified eight serological biomarkers that were associated with frailty, including sgp130, IL-2Rα, I-309, MCP-1, BCA-1, RANTES, leptin, and IL-6R. Frailty Index was inversely predicted by the frequency of CD3+, CD45RA+, and central memory CD4 cells, and positively predicted by the loss of CD28 expression, especially in CD8+ T cells, while frailty status was predicted by the frequency of terminal effector CD8+ T cells. In γ/δ T cells, frailty was negatively associated with CD27, and positively associated with IFNγ+TNFα- secretion by γ/δ2+ cells and IFNγ-TNFα+ secretion by γ/δ2- cells. Increased numbers of exhausted and CD38+ B cells, as well as CD14+CD16+ inflammatory monocytes, were also identified as frailty-associated phenotypes. This pilot study supports an association between inflammation, cellular immunity, and the process of frailty. These findings have significance for the early identification of frailty using circulating biomarkers prior to clinical manifestations of severe functional decline in the elderly. PMID:27119508

  5. Inflammatory and immune markers associated with physical frailty syndrome: findings from Singapore longitudinal aging studies.

    PubMed

    Lu, Yanxia; Tan, Crystal Tze Ying; Nyunt, Ma Shwe Zin; Mok, Esther Wing Hei; Camous, Xavier; Kared, Hassen; Fulop, Tamas; Feng, Liang; Ng, Tze Pin; Larbi, Anis

    2016-05-17

    Chronic systematic inflammation and reduced immune system fitness are considered potential contributing factors to the development of age-related frailty, but the underlying mechanisms are poorly defined. This exploratory study aimed to identify frailty-related inflammatory markers and immunological phenotypes in a cohort of community-dwelling adults aged ≥ 55 years. Frailty was assessed using two models, a Frailty Index and a categorical phenotype, and correlated with levels of circulating immune biomarkers and markers of senescence in immune cell subsets. We identified eight serological biomarkers that were associated with frailty, including sgp130, IL-2Rα, I-309, MCP-1, BCA-1, RANTES, leptin, and IL-6R. Frailty Index was inversely predicted by the frequency of CD3+, CD45RA+, and central memory CD4 cells, and positively predicted by the loss of CD28 expression, especially in CD8+ T cells, while frailty status was predicted by the frequency of terminal effector CD8+ T cells. In γ/δ T cells, frailty was negatively associated with CD27, and positively associated with IFNγ+TNFα- secretion by γ/δ2+ cells and IFNγ-TNFα+ secretion by γ/δ2- cells. Increased numbers of exhausted and CD38+ B cells, as well as CD14+CD16+ inflammatory monocytes, were also identified as frailty-associated phenotypes. This pilot study supports an association between inflammation, cellular immunity, and the process of frailty. These findings have significance for the early identification of frailty using circulating biomarkers prior to clinical manifestations of severe functional decline in the elderly. PMID:27119508

  6. Hyperammonemia and Systemic Inflammatory Response Syndrome Predicts Presence of Hepatic Encephalopathy in Dogs with Congenital Portosystemic Shunts

    PubMed Central

    Tivers, Mickey S.; Handel, Ian; Gow, Adam G.; Lipscomb, Vicky J.; Jalan, Rajiv; Mellanby, Richard J.

    2014-01-01

    Hepatic encephalopathy (HE) is an important cause of morbidity and mortality in patients with liver disease. The pathogenesis of he is incompletely understood although ammonia and inflammatory cytokines have been implicated as key mediators. To facilitate further mechanistic understanding of the pathogenesis of HE, a large number of animal models have been developed which often involve the surgical creation of an anastomosis between the hepatic portal vein and the caudal vena cava. One of the most common congenital abnormalities in dogs is a congenital portosystemic shunt (cpss), which closely mimics these surgical experimental models of HE. Dogs with a cPSS often have clinical signs which mimic clinical signs observed in humans with HE. Our hypothesis is that the pathogenesis of HE in dogs with a cPSS is similar to humans with HE. The aim of the study was to measure a range of clinical, haematological and biochemical parameters, which have been linked to the development of HE in humans, in dogs with a cPSS and a known HE grade. One hundred and twenty dogs with a cPSS were included in the study and multiple regression analysis of clinical, haematological and biochemical variables revealed that plasma ammonia concentrations and systemic inflammatory response syndrome scores predicted the presence of HE. Our findings further support the notion that the pathogenesis of canine and human HE share many similarities and indicate that dogs with cPSS may be an informative spontaneous model of human HE. Further investigations on dogs with cPSS may allow studies on HE to be undertaken without creating surgical models of HE thereby allowing the number of large animals used in animal experimentation to be reduced. PMID:24392080

  7. Levels of Neopterin and other Inflammatory Markers in Obese and Non-Obese Patients with Polycystic Ovary Syndrome

    PubMed Central

    Agacayak, Elif; Tunc, Senem Yaman; Sak, Sibel; Basaranoglu, Serdar; Yüksel, Hatice; Turgut, Abdulkadir; Gul, Talip

    2015-01-01

    Background We aimed to measure the levels of inflammatory markers and neopterin in obese and non-obese patients with PCOS by using 2 separate control groups with matching body mass index (BMI). Material/Methods A total of 60 women of reproductive age with (n=30) and without (n=30) PCOS were included in this study. Based on their BMI, patients with PCOS were divided into 2 groups as obese (n=15) and non-obese (n=15) PCOS groups. In addition, 2 BMI-matched control groups were formed. Neopterin, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (N/L ratio), and vitamin B12 were assessed by complete blood count. Results No significant difference was found between patients with PCOS and control subjects in neopterin, IL-6, TNF-α, and CRP levels. However, N/L ratio levels were significantly higher (p 0.045) and vitamin B12 levels were significantly lower (p 0.033) in patients with PCOS compared to control subjects. No statistically significant difference was found between obese and non-obese patients with PCOS and control subjects in neopterin, IL-6, TNF-α, and N/L ratio levels. However, CRP levels were significantly higher in obese patients with PCOS compared to obese control subjects (p 0.007). Conclusions It can be concluded that inflammatory activity is increased in patients with PCOS, can lead to an increased risk for atherosclerosis, and this increase is not caused by obesity but rather by the polycystic ovary syndrome itself. However, studies with larger sample sizes are needed in this area. PMID:26292090

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

    PubMed Central

    2013-01-01

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

  9. Fitz-Hugh-Curtis syndrome lacking typical characteristics of pelvic inflammatory disease.

    PubMed

    Mitaka, Hayato; Kitazono, Hidetaka; Deshpande, Gautam A; Hiraoka, Eiji

    2016-01-01

    A 23-year-old Japanese woman, previously a commercial sex worker, presented with a 2-day history of right upper quadrant (RUQ) abdominal pain, worse on deep inspiration. She had noticed increased vaginal discharge 2 months earlier and had developed dull, lower abdominal pain 3 weeks prior to presentation. Although pelvic examination and transvaginal ultrasonography revealed neither a tubal nor ovarian pathology, abdominal CT scan with contrast demonstrated early enhancement of the hepatic capsule, a finding pathognomonic for Fitz-Hugh-Curtis syndrome (FHCS). Cervical discharge PCR assay confirmed Chlamydia trachomatis infection. This case highlights that normal gynaecological evaluation may be insufficient to rule out FHCS, for which physicians should have a high index of suspicion when seeing any woman of reproductive age with RUQ pain. PMID:27335367

  10. A rare case of immune reconstitution inflammatory syndrome presenting as secondary syphilis.

    PubMed

    Khatri, Asma; Skalweit, Marion J

    2015-09-01

    Immune reconstitution syndrome has rarely been reported in the context of syphilis infection. We report a patient with AIDS (CD4 42 cells/mm(3), viral load 344,000 cp/ml), treated previously for secondary syphilis and started on an integrase inhibitor-based single-tablet antiretroviral treatment regimen. After four weeks of antiretroviral treatment, he presented with non-tender, non-blanching erythematous nodules on his chest, an elevated rapid plasma reagin (1:1024) and immune reconstitution (CD4 154 cells/mm(3), HIV-RNA 130 cp/ml). A detailed workup to exclude opportunistic infections including secondary and neurosyphilis was performed. The patient was continued on antiretroviral treatment and treated empirically for neurosyphilis given cerebrospinal lymphocytosis and dermatopathology suggesting treponemal antigen-driven B-cell hyperplasia. We favour a diagnosis of immune reconstitution in association with prior syphilis infection attributable to rapid and potent immune restoration afforded by integrase inhibitors.

  11. Palmitoyl acyltransferase DHHC21 mediates endothelial dysfunction in systemic inflammatory response syndrome

    PubMed Central

    Beard, Richard S.; Yang, Xiaoyuan; Meegan, Jamie E.; Overstreet, Jonathan W.; Yang, Clement G.Y.; Elliott, John A.; Reynolds, Jason J.; Cha, Byeong J.; Pivetti, Christopher D.; Mitchell, David A.; Wu, Mack H.; Deschenes, Robert J.; Yuan, Sarah Y.

    2016-01-01

    Endothelial dysfunction is a hallmark of systemic inflammatory response underlying multiple organ failure. Here we report a novel function of DHHC-containing palmitoyl acyltransferases (PATs) in mediating endothelial inflammation. Pharmacological inhibition of PATs attenuates barrier leakage and leucocyte adhesion induced by endothelial junction hyperpermeability and ICAM-1 expression during inflammation. Among 11 DHHCs detected in vascular endothelium, DHHC21 is required for barrier response. Mice with DHHC21 function deficiency (Zdhhc21dep/dep) exhibit marked resistance to injury, characterized by reduced plasma leakage, decreased leucocyte adhesion and ameliorated lung pathology, culminating in improved survival. Endothelial cells from Zdhhc21dep/dep display blunted barrier dysfunction and leucocyte adhesion, whereas leucocytes from these mice did not show altered adhesiveness. Furthermore, inflammation enhances PLCβ1 palmitoylation and signalling activity, effects significantly reduced in Zdhhc21dep/dep and rescued by DHHC21 overexpression. Likewise, overexpression of wild-type, not mutant, PLCβ1 augments barrier dysfunction. Altogether, these data suggest the involvement of DHHC21-mediated PLCβ1 palmitoylation in endothelial inflammation. PMID:27653213

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

    PubMed Central

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

    1988-01-01

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

  13. Integrated Haematological Profiles of Redox Status, Lipid, and Inflammatory Protein Biomarkers in Benign Obesity and Unhealthy Obesity with Metabolic Syndrome

    PubMed Central

    Lubrano, Carla; Valacchi, Giuseppe; Specchia, Palma; Gnessi, Lucio; Rubanenko, Elizaveta P.; Shuginina, Elena A.; Trukhanov, Arseny I.; Korkina, Liudmila G.; De Luca, Chiara

    2015-01-01

    The pathogenesis of obesity (OB) and metabolic syndrome (MetS) implies free radical-, oxidized lipid- (LOOH-), and inflammatory cytokine-mediated altered pathways in target organs. Key elements of the transition from benign OB to unhealthy OB+MetS remain unclear. Here, we measured a panel of redox, antioxidant, and inflammation markers in the groups of OB patients (67 with, 45 without MetS) and 90 controls. Both OB groups displayed elevated levels of adipokines and heavy oxidative stress (OS) evidenced by reduced levels of glutathione, downregulated glutathione-S-transferase, increased 4-hydroxynonenal-protein adducts, reactive oxygen species, and membrane-bound monounsaturated fatty acids (MUFA). Exclusively in OB+MetS, higher-than-normal glutathione peroxidase activity, tumor necrosis factor-α, and other proinflammatory cytokines/chemokines/growth factors were observed; a combination of high adipokine plasminogen activator inhibitor-1 and MUFA was consistent with increased cardiovascular risk. The uncomplicated OB group showed features of adaptation to OS such as decreased levels of vitamin E, activated superoxide dismutase, and inhibited catalase, suggesting H2O2 hyperproduction. Proinflammatory cytokine pattern was normal, except few markers like RANTES, a suitable candidate for therapeutic approaches to prevent a setting of MetS by inhibition of LOOH-primed leukocyte chemotaxis/recruitment to target tissues. PMID:26090072

  14. Leishmaniasis as a Manifestation of Immune Reconstitution Inflammatory Syndrome (IRIS) in HIV-Infected Patients: A Literature Review

    PubMed Central

    Badaró, Roberto; Gonçalves, Larissa O.; Gois, Luana L.; Maia, Zuinara Pereira Gusmão; Benson, Constance; Grassi, Maria Fernanda Rios

    2016-01-01

    Introduction After the onset of highly active antiretroviral therapy (HAART), some HIV-infected patients present a severe inflammation in response to a latent or a previously treated opportunistic pathogen termed immune reconstitution inflammatory syndrome (IRIS). Few reports of tegumentary and visceral leishmaniasis have been described in association with IRIS. Methods A systematic literature review of IRIS in association with leishmaniasis identified 34 reported cases. Results and Discussion The majority of these occurred in males 4 months following the onset of HAART. The mean CD4 count before HAART was 94 ± 77 cells/mm3, increasing to 5 times the initial value between the onset of HAART and IRIS presentation. Visceral leishmaniasis and post–kala-azar dermal leishmaniasis were the most commonly reported clinical manifestations, followed by tegumentary leishmaniasis and uveitis. Conclusions Commonly found characteristics included cutaneous involvement, regardless of Leishmania species; appearance of lesions unrelated to time of probable Leishmania infection; rapid recovery of CD4 count following HAART; and rapid progression. PMID:25331225

  15. Exploration of eosinopenia as a diagnostic parameter to differentiate sepsis from systemic inflammatory response syndrome: Results from an observational study

    PubMed Central

    Anand, Dimple; Ray, Sumit; Bhargava, Seema; Srivastava, Lalit M.; Garg, Ashish; Gafoor, Imran; Singh, Rahul; Dhar, Debashish

    2016-01-01

    Aim of the Study: Initial differentiation of sepsis from systemic inflammatory response syndrome (SIRS) is of prime importance for early institution of appropriate treatment. This study aimed to compare the differential diagnostic efficacy of absolute eosinophil count (AEC - a routinely available economic marker) with total leukocyte count (TLC) and procalcitonin (PCT - a costly marker available only in specialized settings). Materials and Methods: In this prospective observational study, 170 patients of sepsis (severe sepsis = 125; SIRS = 45) were enrolled. AEC, TLC, and PCT were measured in the blood of all patients at the time of admission and data analyzed statistically. Results: Median AEC was 0 cells/mm3 in both SIRS and sepsis. TLC and PCT levels were significantly higher (P < 0.001) in culture negative, culture positive, and overall sepsis groups in comparison to SIRS group. At a cutoff of < 50 cells/mm3, AEC demonstrated a sensitivity and specificity of 23% and 68%, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of TLC were 57%, 71%, 85%, 37% and of PCT were 82.4%, 82.2%, 93%, and 63%, respectively with area under curve of 0.455 for AEC, 0.640 for TLC, 0.908 for PCT. Conclusions: This study suggests that eosinopenia is not a reliable diagnostic tool to differentiate sepsis from SIRS. PCT and TLC are better differential diagnostic biomarkers. PMID:27275077

  16. Associations among Gut Permeability, Inflammatory Markers and Symptoms in Patients with Irritable Bowel Syndrome

    PubMed Central

    Shulman, Robert J.; Jarrett, Monica E.; Cain, Kevin C.; Broussard, Elizabeth; Heitkemper, Margaret M.

    2014-01-01

    Background Alterations in gastrointestinal (GI) permeability and immune measures are present in some patients with irritable bowel syndrome (IBS) but the relationship to symptoms is poorly defined. In adults with IBS, we compared permeability, unstimulated peripheral blood monocyte (PBMC) interleukin-10 (IL-10) levels, IBS life interference, and gastrointestinal (GI) and psychological distress symptoms. Methods In 88 women and 18 men with IBS, GI permeability was quantitated as percent recovery of urinary sucrose and the lactulose/mannitol (L/M) ratio. IL-10 was measured in supernatants from 72-hour incubated, unstimulated PBMCs. Participants completed a 4-week daily diary recording IBS life interference on daily activities and work, IBS symptoms, and psychological distress symptoms. They also completed the Brief Symptom Inventory and Composite International Diagnostic Interview. Results The L/M ratio but not percent sucrose recovery was significantly correlated with IBS interference with activities and work and retrospectively measured anxiety and depression. Unstimulated PBMC production of IL-10 correlated significantly with IBS interference with daily work, IBS symptom score, and abdominal pain. We identified a subgroup of IBS subjects with higher IL-10 and/or higher L/M ratio who had substantially higher IBS interference and IBS symptom scores. Conclusions Our findings suggest a distinct subgroup of IBS patients with alterations in gut barrier function. This subgroup is characterized by increased GI permeability and/or increased PBMC production of IL-10. These physiologic alterations reflect more severe IBS as measured by interference of IBS with daily activities and daily IBS symptoms. PMID:24435814

  17. Postural Orthostatic Tachycardia With Chronic Fatigue After HPV Vaccination as Part of the "Autoimmune/Auto-inflammatory Syndrome Induced by Adjuvants": Case Report and Literature Review.

    PubMed

    Tomljenovic, Lucija; Colafrancesco, Serena; Perricone, Carlo; Shoenfeld, Yehuda

    2014-01-01

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

  18. Comparison of the systemic inflammatory response syndrome between monomicrobial and polymicrobial Pseudomonas aeruginosa nosocomial bloodstream infections

    PubMed Central

    Marra, Alexandre R; Bearman, Gonzalo ML; Wenzel, Richard P; Edmond, Michael B

    2005-01-01

    Background Some studies of nosocomial bloodstream infection (nBSI) have demonstrated a higher mortality for polymicrobial bacteremia when compared to monomicrobial nBSI. The purpose of this study was to compare differences in systemic inflammatory response and mortality between monomicrobial and polymicrobial nBSI with Pseudomonas aeruginosa. Methods We performed a historical cohort study on 98 adults with P. aeruginosa (Pa) nBSI. SIRS scores were determined 2 days prior to the first positive blood culture through 14 days afterwards. Monomicrobial (n = 77) and polymicrobial BSIs (n = 21) were compared. Results 78.6% of BSIs were caused by monomicrobial P. aeruginosa infection (MPa) and 21.4% by polymicrobial P. aeruginosa infection (PPa). Median APACHE II score on the day of BSI was 22 for MPa and 23 for PPa BSIs. Septic shock occurred in 33.3% of PPa and in 39.0% of MPa (p = 0.64). Progression to septic shock was associated with death more frequently in PPa (OR 38.5, CI95 2.9–508.5) than MPa (OR 4.5, CI95 1.7–12.1). Maximal SIR (severe sepsis, septic shock or death) was seen on day 0 for PPa BSI vs. day 1 for MPa. No significant difference was noted in the incidence of organ failure, 7-day or overall mortality between the two groups. Univariate analysis revealed that APACHE II score ≥20 at BSI onset, Charlson weighted comorbidity index ≥3, burn injury and respiratory, cardiovascular, renal and hematologic failure were associated with death, while age, malignant disease, diabetes mellitus, hepatic failure, gastrointestinal complications, inappropriate antimicrobial therapy, infection with imipenem resistant P. aeruginosa and polymicrobial nBSI were not. Multivariate analysis revealed that hematologic failure (p < 0.001) and APACHE II score ≥20 at BSI onset (p = 0.005) independently predicted death. Conclusion In this historical cohort study of nBSI with P. aeruginosa, the incidence of septic shock and organ failure was high in both groups. Additionally

  19. Temperature variability analysis using wavelets and multiscale entropy in patients with systemic inflammatory response syndrome, sepsis, and septic shock

    PubMed Central

    2012-01-01

    Background Even though temperature is a continuous quantitative variable, its measurement has been considered a snapshot of a process, indicating whether a patient is febrile or afebrile. Recently, other diagnostic techniques have been proposed for the association between different properties of the temperature curve with severity of illness in the Intensive Care Unit (ICU), based on complexity analysis of continuously monitored body temperature. In this study, we tried to assess temperature complexity in patients with systemic inflammation during a suspected ICU-acquired infection, by using wavelets transformation and multiscale entropy of temperature signals, in a cohort of mixed critically ill patients. Methods Twenty-two patients were enrolled in the study. In five, systemic inflammatory response syndrome (SIRS, group 1) developed, 10 had sepsis (group 2), and seven had septic shock (group 3). All temperature curves were studied during the first 24 hours of an inflammatory state. A wavelet transformation was applied, decomposing the signal in different frequency components (scales) that have been found to reflect neurogenic and metabolic inputs on temperature oscillations. Wavelet energy and entropy per different scales associated with complexity in specific frequency bands and multiscale entropy of the whole signal were calculated. Moreover, a clustering technique and a linear discriminant analysis (LDA) were applied for permitting pattern recognition in data sets and assessing diagnostic accuracy of different wavelet features among the three classes of patients. Results Statistically significant differences were found in wavelet entropy between patients with SIRS and groups 2 and 3, and in specific ultradian bands between SIRS and group 3, with decreased entropy in sepsis. Cluster analysis using wavelet features in specific bands revealed concrete clusters closely related with the groups in focus. LDA after wrapper-based feature selection was able to classify

  20. Systemic Inflammatory Response Syndrome after Contentious-Flow Left Ventricular Assist Device Implantation and Change in Platelet Mitochondrial Membrane Potential

    PubMed Central

    Mondal, Nandan K.; Sorensen, Erik N.; Feller, Erika D.; Pham, Si M.; Griffith, Bartley P.; Wu, Zhongjun J.

    2015-01-01

    Background The objective of this study was to investigate the change of platelet function and platelet mitochondrial membrane potential in contentious-flow left ventricular assist device (CF-LVAD) implanted heart failure (HF) patients with or without systemic inflammatory response syndrome (SIRS). Methods and Results We recruited 31 CF-LVAD patients (16 SIRS and 15 Non-SIRS) and 11 healthy volunteers as the control. Pre and post implant blood samples were collected. We used PFA-100 to test the platelet functionality. Mitochondrial potential sensitive dye was used to detect platelet dysfunction (ΔΨm) via flow cytometry. The percentage of depolarized ΔΨm platelets was found to be pre-existing conditions in all HF patients prior to CF-LVAD implantation compared to controls (10.3±6.3vs.2.8±2.2%,p<0.001). As evident from PFA-100 test, The HF patients who developed SIRS after CF-LVAD implantation had significantly higher qualitative platelet defects and thrombocytopathies compared to baseline level. After implantation, the depolarized platelets in the SIRS patients increased by 2-fold compared to the baseline (18.2±8.4vs.9.0±6.6%,p<0.01); while no change was noticed in the Non-SIRS patients (10.9±6.2vs.11.7±5.8%,p=0.75). Conclusions We identified that the platelet function and mitochondrial damage were enhanced in CFLVAD patients with SIRS. Our findings suggest that depolarization of mitochondrial membrane potential is associated with SIRS after CF-LVAD implant surgery. PMID:25921521

  1. Presence of Systemic Inflammatory Response Syndrome Predicts a Poor Clinical Outcome in Dogs with a Primary Hepatitis.

    PubMed

    Kilpatrick, Scott; Dreistadt, Margaret; Frowde, Polly; Powell, Roger; Milne, Elspeth; Smith, Sionagh; Morrison, Linda; Gow, Adam G; Handel, Ian; Mellanby, Richard J

    2016-01-01

    Primary hepatopathies are a common cause of morbidity and mortality in dogs. The underlying aetiology of most cases of canine hepatitis is unknown. Consequently, treatments are typically palliative and it is difficult to provide accurate prognostic information to owners. In human hepatology there is accumulating data which indicates that the presence of systemic inflammatory response syndrome (SIRS) is a common and debilitating event in patients with liver diseases. For example, the presence of SIRS has been linked to the development of complications such as hepatic encephalopathy (HE) and is associated with a poor clinical outcome in humans with liver diseases. In contrast, the relationship between SIRS and clinical outcome in dogs with a primary hepatitis is unknown. Seventy dogs with histologically confirmed primary hepatitis were enrolled into the study. Additional clinical and clinicopathological information including respiratory rate, heart rate, temperature, white blood cell count, sodium, potassium, sex, presence of ascites, HE score, alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin and red blood cell concentration were available in all cases. The median survival of dogs with a SIRS score of 0 or 1 (SIRS low) was 231 days compared to a median survival of 7 days for dogs with a SIRS score of 2, 3 or 4 (SIRS high) (p<0.001). A Cox proportional hazard model, which included all other co-variables, revealed that a SIRS high score was an independent predictor of a poor clinical outcome. The effect of modulating inflammation on treatment outcomes in dogs with a primary hepatitis is deserving of further study. PMID:26808672

  2. Presence of Systemic Inflammatory Response Syndrome Predicts a Poor Clinical Outcome in Dogs with a Primary Hepatitis.

    PubMed

    Kilpatrick, Scott; Dreistadt, Margaret; Frowde, Polly; Powell, Roger; Milne, Elspeth; Smith, Sionagh; Morrison, Linda; Gow, Adam G; Handel, Ian; Mellanby, Richard J

    2016-01-01

    Primary hepatopathies are a common cause of morbidity and mortality in dogs. The underlying aetiology of most cases of canine hepatitis is unknown. Consequently, treatments are typically palliative and it is difficult to provide accurate prognostic information to owners. In human hepatology there is accumulating data which indicates that the presence of systemic inflammatory response syndrome (SIRS) is a common and debilitating event in patients with liver diseases. For example, the presence of SIRS has been linked to the development of complications such as hepatic encephalopathy (HE) and is associated with a poor clinical outcome in humans with liver diseases. In contrast, the relationship between SIRS and clinical outcome in dogs with a primary hepatitis is unknown. Seventy dogs with histologically confirmed primary hepatitis were enrolled into the study. Additional clinical and clinicopathological information including respiratory rate, heart rate, temperature, white blood cell count, sodium, potassium, sex, presence of ascites, HE score, alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin and red blood cell concentration were available in all cases. The median survival of dogs with a SIRS score of 0 or 1 (SIRS low) was 231 days compared to a median survival of 7 days for dogs with a SIRS score of 2, 3 or 4 (SIRS high) (p<0.001). A Cox proportional hazard model, which included all other co-variables, revealed that a SIRS high score was an independent predictor of a poor clinical outcome. The effect of modulating inflammation on treatment outcomes in dogs with a primary hepatitis is deserving of further study.

  3. Autoimmune/auto-inflammatory syndrome induced by adjuvants (ASIA) after quadrivalent human papillomavirus vaccination in Colombians: a call for personalised medicine.

    PubMed

    Anaya, Juan-Manuel; Reyes, Benjamin; Perdomo-Arciniegas, Ana M; Camacho-Rodríguez, Bernardo; Rojas-Villarraga, Adriana

    2015-01-01

    This was a case study in which 3 patients with autoimmune/auto-inflammatory syndrome induced by adjuvants (ASIA) after quadrivalent human papillomavirus vaccination (HPV) were evaluated and described. All the patients were women. Diagnosis consisted of HLA-B27 enthesitis related arthritis, rheumatoid arthritis and systemic lupus erythematous, respectively. Our results highlight the risk of developing ASIA after HPV vaccination and may serve to increase the awareness of such a complication. Factors that are predictive of developing autoimmune diseases should be examined at the population level in order to establish preventive measures in at-risk individuals for whom healthcare should be personalized and participatory.

  4. The Role of Granulocyte Colony-Stimulating Factor in the Neutrophilia Observed in the Fetal Inflammatory Response Syndrome

    PubMed Central

    Chaiworapongsa, Tinnakorn; Romero, Roberto; Berry, Stanley M.; Hassan, Sonia S.; Yoon, Bo Hyun; Edwin, Samuel; Mazor, Moshe

    2012-01-01

    OBJECTIVE Fetal neutrophilia is present in two-thirds of cases with the fetal inflammatory response syndrome (FIRS). The mechanisms responsible for this finding have not been elucidated. Granulocyte Colony-Stimulating Factor (G-CSF) is the primary physiologic regulator of neutrophil production and plays a key role in the rapid generation and release of neutrophils in stressful conditions (i.e., infection). The objective of this study was to determine: 1) whether FIRS was associated with changes in fetal plasma G-CSF concentrations; and 2) if fetal plasma G-CSF concentrations correlated with fetal neutrophil counts, chorioamnionitis, neonatal morbidity/mortality and cordocentesis-to-delivery interval. STUDY DESIGN Percutaneous umbilical cord blood sampling was performed in a population of patients with preterm labor (n=107). A fetal plasma interleukin-6 (IL-6) concentration >11 pg/mL was used to define FIRS. Cord blood G-CSF was measured by a sensitive and specific immunoassay. An absolute neutrophil count was determined and corrected for gestational age. Receiver operating characteristic (ROC) curve, survival analysis and Cox proportional hazard model were employed. RESULTS 1) G-CSF was detected in all fetal blood samples; 2) fetuses with FIRS had a higher median fetal plasma G-CSF concentration than those without FIRS (p<0.001); 3) a fetal plasma G-CSF concentration ≥134 pg/mL (derived from an ROC curve) was associated with a shorter cordocentesis-to-delivery interval, a higher frequency of chorioamnionitis (clinical and histological), intra-amniotic infection, and composite neonatal morbidity/mortality than a fetal plasma concentration below this cut-off; and 4) a fetal plasma G-CSF concentration ≥134 pg/mL was associated with a shorter cordocentesis-to-delivery interval (hazard ratio 3.2; 95% confidence interval 1.8-5.8) after adjusting for confounders. CONCLUSIONS 1) G-CSF concentrations are higher in the peripheral blood of fetuses with FIRS than in

  5. Identification of genetic loci for basal cell nevus syndrome and inflammatory bowel disease in a single large pedigree.

    PubMed

    Panhuysen, Carolien I; Karban, Amir; Knodle Manning, Alisa; Bayless, Theodore M; Duerr, Richard H; Bailey-Wilson, Joan E; Epstein, Ervin H; Brant, Steven R

    2006-08-01

    Basal Cell Nevus Syndrome (BCNS) is an autosomal dominant disease. PTCH1 gene mutations have been found responsible in many but not all pedigrees. Inflammatory Bowel Disease (IBD) is a complex genetic disorder, disproportionate in Ashkenazim, and characterized by chronic intestinal inflammation. We revisited a large Ashkenazim pedigree, first reported in 1968, with multiple diagnoses of BCNS and IBD, and with a common genetic cause for both disorders proposed. We expanded the pedigree to four generations and performed a genome-wide linkage study for BCNS and IBD traits. Twelve members with BCNS, seven with IBD, five with both diagnoses and eight unaffected were genotyped. Both non-parametric (GENEHUNTER 2.1) and parametric (FASTLINK) linkage analyses were performed and a validation through simulation was performed. BCNS linked to chromosome 9q22 (D9S1120) just proximal to the PTCH1 gene (NPL=3.26, P=0.003; parametric two-point LOD=2.4, parametric multipoint LOD=3.7). Novel IBD linkage evidence was observed at chromosome 1p13 (D1S420, NPL 3.92, P=0.0047; parametric two-point LOD=1.9). Linkage evidence was also observed to previously reported IBD loci on 4q, (D4S2623, NPL 3.02, P=0.012; parametric two-point LOD=2.15), 10q23 (D10S1225 near DLG5, NPL 3.33, P=0.0085; parametric two-point LOD=1.3), 12 overlapping the IBD2 locus (D12S313, NPL 2.6, P=0.018; parametric two-point LOD=1.52), and 7q (D7S510 and D7S3046, NPL 4.06, P=0.0035; parametric two-point LOD=2.18). In this pedigree affected by both BCNS and IBD, the two traits and their respective candidate genetic loci segregate independently; BCNS maps to the PTCH1 gene and IBD maps to several candidate regions, mostly overlapping previously observed IBD loci. PMID:16733713

  6. Steroids are a risk factor for Kaposi's sarcoma-immune reconstitution inflammatory syndrome and mortality in HIV infection

    PubMed Central

    Fernández-Sánchez, Mónica; Iglesias, María C.; Ablanedo-Terrazas, Yuria; Ormsby, Christopher E.; Alvarado-de la Barrera, Claudia; Reyes-Terán, Gustavo

    2016-01-01

    Objectives: To investigate the association between Kaposi's sarcoma-associated immune reconstitution inflammatory syndrome (KS-IRIS) and mortality, with the use of glucocorticoids in HIV-infected individuals. Design: Case–control study. Methods: We reviewed the medical records of 145 individuals with HIV-associated Kaposi's sarcoma receiving antiretroviral therapy. The association of different variables with KS-IRIS and Kaposi's sarcoma-related mortality was explored by univariate and multivariate analyses. The main exposure of interest was the use of glucocorticoids. We also compared the time to KS-IRIS and the time to death of individuals treated with glucocorticoids vs. those nontreated with glucocorticoids, and the time to death of individuals with KS-IRIS vs. those without KS-IRIS by hazards regression. Results: Sixty of 145 individuals received glucocorticoids (41.4%) for the management or suspicion of Pneumocystis jirovecii pneumonia. Fifty individuals had KS-IRIS (37%). The use of glucocorticoids was more frequent in individuals with KS-IRIS than in those without KS-IRIS (54.9 vs. 36.47%, P = 0.047). Kaposi's sarcoma-related mortality occurred in 17 cases (11.7%), and glucocorticoid use was more frequent in this group (76.47 vs. 36.7%, P = 0.003). Glucocorticoid use was a risk factor for mortality (adjusted odds ratio = 4.719, 95% confidence interval = 1.383–16.103, P = 0.0132), and was associated with shorter periods to KS-IRIS (P = 0.03) and death (P = 0.0073). KS-IRIS was a risk factor for mortality (P = 0.049). Conclusion: In HIV-infected individuals, the use of glucocorticoids is a risk factor for KS-IRIS and Kaposi's sarcoma-associated mortality. In addition, KS-IRIS is a risk factor for mortality. Therefore, glucocorticoid administration in this population requires careful consideration based on individualized risk–benefit analysis. PMID:26636923

  7. Inflammatory cytokines imbalance in the very early phase of acute coronary syndrome: correlations with angiographic findings and in-hospital events.

    PubMed

    Brunetti, Natale Daniele; Munno, Irene; Pellegrino, Pier Luigi; Ruggero, Vincenzo; Correale, Michele; De Gennaro, Luisa; Cuculo, Andrea; Campanale, Erasmo Giulio; Di Biase, Matteo

    2011-02-01

    The aim of this study is to investigate the release of some inflammatory cytokines (Cks) during the very early phase (first 24 h) of acute coronary syndrome (ACS). Twenty-six consecutive subjects admitted to coronary care unit with ACS underwent serial blood sampling in order to evaluate concentrations of interleukin (IL)-2, IL-10, IL-18, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ. Blood samples were taken within 6 h after onset of chest pain (T₀), at 12 h (T₁), and at 24 h (T₂). Patients were thus divided into four groups comparing pro-inflammatory Ck release (IL-2, TNF-α, and IFN-γ) and anti-inflammatory activity (IL-10). Clinical features, risk factors, incidence of adverse events, and coronary angiography findings were compared with Ck activation. Ck levels were significantly increased if compared with baseline. Subjects with marked inflammatory response showed a higher incidence of left anterior descending coronary disease (IL-2, p < 0.001; TNF-α and IFN-γ, p < 0.05) and more often incurred early complications (IL-2, p < 0.05; IFN-γ, p < 0.001). A correlation was detectable between IL-18 levels and myocardial enzyme release (creatine kinase, r = 0.47; lactate dehydrogenase, r = 0.54; troponin I, r = 0.58; p < 0.05). TNF-α levels were associated with a worse prognosis at follow-up (Log rank, p < 0.05). A Ck activation characterizes the early phase of ACS. Early inflammatory reaction seems to correlate with coronary disease and adverse events.

  8. Activation of Adenosine 2A receptor inhibits neutrophil apoptosis in an autophagy-dependent manner in mice with systemic inflammatory response syndrome

    PubMed Central

    Liu, Yang-Wuyue; Yang, Ting; Zhao, Li; Ni, Zhenhong; Yang, Nan; He, Fengtian; Dai, Shuang-Shuang

    2016-01-01

    Systemic inflammatory response syndrome (SIRS) is an overwhelming whole body inflammation caused by infectious diseases or sterile insults. Neutrophils are the dominant participants during inflammation, and their survival and death determine the initiation as well as resolution of SIRS. Apoptosis and autophagy are two fundamental cellular processes that modulating cell fate, but their correlation and regulators in neutrophils under SIRS condition have not been elucidated. In this study, we demonstrated that high dose of LPS induced both apoptosis and autophagy of neutrophils in a mouse SIRS model and LPS-stimulated neutrophils in vitro. Moreover, we found that the adenosine 2A receptor (A2AR), a known anti-inflammatory G protein-coupled receptor (GPCR), could inhibit LPS-induced neutrophil apoptosis by suppressing the LPS-induced autophagy. Activation of A2AR suppressed LPS-induced autophagy by inhibiting the ROS-JNK pathway as well as promoting GPCR βϒ subunit–AKT signaling. The A2AR-inhibited autophagy suppressed apoptosis of neutrophils by blocking caspase8, caspase3 and PARP signaling. These findings not only increase our understandings of neutrophils’ fate and function in response to systemic inflammation, but also identify a novel anti-inflammatory role of A2AR in modulating neutrophils’ survival during inflammation. PMID:27647162

  9. A Trypsin Inhibitor from Tamarind Reduces Food Intake and Improves Inflammatory Status in Rats with Metabolic Syndrome Regardless of Weight Loss

    PubMed Central

    Carvalho, Fabiana M. C.; Lima, Vanessa C. O.; Costa, Izael S.; Medeiros, Amanda F.; Serquiz, Alexandre C.; Lima, Maíra C. J. S.; Serquiz, Raphael P.; Maciel, Bruna L. L.; Uchôa, Adriana F.; Santos, Elizeu A.; Morais, Ana H. A.

    2016-01-01

    Trypsin inhibitors are studied in a variety of models for their anti-obesity and anti-inflammatory bioactive properties. Our group has previously demonstrated the satietogenic effect of tamarind seed trypsin inhibitors (TTI) in eutrophic mouse models and anti-inflammatory effects of other trypsin inhibitors. In this study, we evaluated TTI effect upon satiety, biochemical and inflammatory parameters in an experimental model of metabolic syndrome (MetS). Three groups of n = 5 male Wistar rats with obesity-based MetS received for 10 days one of the following: (1) Cafeteria diet; (2) Cafeteria diet + TTI (25 mg/kg); and (3) Standard diet. TTI reduced food intake in animals with MetS. Nevertheless, weight gain was not different between studied groups. Dyslipidemia parameters were not different with the use of TTI, only the group receiving standard diet showed lower very low density lipoprotein (VLDL) and triglycerides (TG) (Kruskal–Wallis, p < 0.05). Interleukin-6 (IL-6) production did not differ between groups. Interestingly, tumor necrosis factor-alpha (TNF-α) was lower in animals receiving TTI. Our results corroborate the satietogenic effect of TTI in a MetS model. Furthermore, we showed that TTI added to a cafeteria diet may decrease inflammation regardless of weight loss. This puts TTI as a candidate for studies to test its effectiveness as an adjuvant in MetS treatment. PMID:27690087

  10. Grape consumption increases anti-inflammatory markers and upregulates peripheral nitric oxide synthase in the absence of dyslipidemias in men with metabolic syndrome.

    PubMed

    Barona, Jacqueline; Blesso, Christopher N; Andersen, Catherine J; Park, Youngki; Lee, Jiyoung; Fernandez, Maria Luz

    2012-12-06

    We evaluated the effects of grape consumption on inflammation and oxidation in the presence or absence of dyslipidemias in metabolic syndrome (MetS). Men with MetS (n = 24), 11 with high triglycerides and low HDL and 13 with no dyslipidemia were recruited and randomly allocated to consume daily either 46 g of lyophilized grape powder (GRAPE), equivalent to 252 g fresh grapes, or placebo with an identical macronutrient composition and caloric value as GRAPE for four weeks. After a three-week washout, participants followed the alternate treatment. We measured changes between placebo and GRAPE periods in inflammatory and oxidative stress markers both in circulation and in gene expression. Changes in plasma adiponectin (p < 0.05), interleukin (IL)-10 (p < 0.005) and in mRNA expression of the inducible isoform of nitric oxide synthase (iNOS) (p < 0.25) were increased in the GRAPE compared to the placebo period only in those individuals without dyslipidemia. Additionally, plasma IL-10 was negatively correlated with NOX2 expression, a marker of oxidative stress (r = -0.55, p < 0.01), while iNOS expression was positively correlated with the expression of superoxide dismutase 2 (r = 0.642, p < 0.01), a key anti-oxidative enzyme. Grape consumption displayed anti-oxidative and increased anti-inflammatory markers in the absence of the inflammatory milieu associated with dyslipidemias.

  11. Activation of Adenosine 2A receptor inhibits neutrophil apoptosis in an autophagy-dependent manner in mice with systemic inflammatory response syndrome.

    PubMed

    Liu, Yang-Wuyue; Yang, Ting; Zhao, Li; Ni, Zhenhong; Yang, Nan; He, Fengtian; Dai, Shuang-Shuang

    2016-01-01

    Systemic inflammatory response syndrome (SIRS) is an overwhelming whole body inflammation caused by infectious diseases or sterile insults. Neutrophils are the dominant participants during inflammation, and their survival and death determine the initiation as well as resolution of SIRS. Apoptosis and autophagy are two fundamental cellular processes that modulating cell fate, but their correlation and regulators in neutrophils under SIRS condition have not been elucidated. In this study, we demonstrated that high dose of LPS induced both apoptosis and autophagy of neutrophils in a mouse SIRS model and LPS-stimulated neutrophils in vitro. Moreover, we found that the adenosine 2A receptor (A2AR), a known anti-inflammatory G protein-coupled receptor (GPCR), could inhibit LPS-induced neutrophil apoptosis by suppressing the LPS-induced autophagy. Activation of A2AR suppressed LPS-induced autophagy by inhibiting the ROS-JNK pathway as well as promoting GPCR βϒ subunit-AKT signaling. The A2AR-inhibited autophagy suppressed apoptosis of neutrophils by blocking caspase8, caspase3 and PARP signaling. These findings not only increase our understandings of neutrophils' fate and function in response to systemic inflammation, but also identify a novel anti-inflammatory role of A2AR in modulating neutrophils' survival during inflammation. PMID:27647162

  12. The role of free fatty acids in the inflammatory and cardiometabolic profile in adolescents with metabolic syndrome engaged in interdisciplinary therapy.

    PubMed

    Masquio, Deborah Cristina Landi; de Piano-Ganen, Aline; Oyama, Lila Missae; Campos, Raquel Munhoz da Silveira; Santamarina, Aline Boveto; de Souza, Gabriel Inácio de Morais Honorato; Gomes, Aline Dal'Olio; Moreira, Renata Guimarães; Corgosinho, Flávia Campos; do Nascimento, Claudia Maria Oller; Tock, Lian; Tufik, Sergio; de Mello, Marco Túlio; Dâmaso, Ana R

    2016-07-01

    The purpose of the present study was to evaluate if interdisciplinary therapy can influence the cardiometabolic and serum free fatty acid profile. The second aim was to evaluate if there is an association between serum free fatty acids, inflammation and cardiometabolic biomarkers in obese adolescents with and without metabolic syndrome submitted to a long-term interdisciplinary therapy. The study involved 108 postpuberty obese adolescents, who were divided according to metabolic syndrome (MetS) diagnosis: MetS (n=32) and Non-MetS (n=76). The interdisciplinary therapy consisted of a 1-year period of nutrition, psychology, physical exercise and clinical support. After therapy, both groups improved metabolic, inflammatory (leptin, adiponectin, leptin/adiponectin ratio, adiponectin/leptin ratio and C-reactive protein) and cardiometabolic profile (PAI-1 and ICAM). Metabolic syndrome prevalence reduced from 28.70% to 12.96%. Both groups reduced myristic acid (C14:0) and increased docosahexaenoic acid (DHA, C22:6n3), heneicosapentaenoic acid (HPA, C21:5n3) and arachidonic acid (C20:4n6). After adjustment for metabolic syndrome and the number of metabolic syndrome parameters, multiple regression analysis showed that changes in VCAM and PAI-1 were negatively associated with changes in cis-linoleic acid (C18:2n6c). Additionally, changes in trans-linoleic acid (C18:2n6t) were also positively associated with these biomarkers. Moreover, leptin and leptin/adiponectin ratio were negatively associated with changes in docosapentaenoic acid (DPA, C22:5n3) and stearidonic acid (SDA, C18:4n3). Adiponectin/leptin ratio was positively associated with docosapentaenoic acid (DPA, C22:5n3). Changes in adiponectin were positively correlated with changes in omega 3, such as heneicosapentaenoic acid (HPA, C21:5n3) and docosapentaenoic acid (DPA, C22:5n3). Results support that interdisciplinary therapy can control inflammatory and cardiometabolic profile in obese adolescents. Moreover, serum

  13. [The influence of immunocorrection on the state of the anti-endotoxin immunity in children with systemic inflammatory response syndrome and gram-negative infection].

    PubMed

    Pritulo, L F

    2009-05-01

    There were examined 34 children, in whom systemic inflammatory answer syndrome (SIAS) was diagnosed. In 16 children pathogenetically substantiated immunocorrection, using donor's plasma, enhanced by antibodies (AB) to endotoxin (ET), was conducted; in 18 children--the conventional complex therapy. While presence of gram-negative infection in children, suffering SIAS, the activation o the inborn nonspeciphic factors (LBP, sCD14) and speciphic low-affinic AB (anti-ET-IgM, anti-ET-IgA) the antiendotoxin immunity in combination with selective immunodeficiency of anti-ET-IgG were revealed. While the donor's plasm application, enhanced by AB to ET, the titer of anti-ET-IgG, anti-ET-IgM, anti-ET-IgA and LBP have had achieved normal values and did not differ from such in the control on the 14th day.

  14. Studies of HLA associations in male and female patients with Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).

    PubMed

    McCombe, Pamela A; Csurhes, Peter A; Greer, Judith M

    2006-11-01

    HLA associations are found to differ with the gender of the patient in some autoimmune diseases. Here we have investigated whether there are gender-related HLA associations in Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), both of which occur more frequently in male patients than in females. In GBS, no particular HLA associations were noted, except for a slight negative association in both males and females for carriage of HLA-DR5. In CIDP, the gene frequency and the frequency of individuals positive for HLA-DR2 were greater in female patients than female controls, although this was statistically significant only for the gene frequency. Furthermore more female CIDP patients were homozygous for DR2, than male CIDP patients, or male or female controls and patients with GBS. This suggests that sex-related factors may interact with the risk associated with carriage of HLA-DR2 for development of CIDP.

  15. Choriodecidual inflammatory syndrome (CoDIS) is the leading, and under recognised, cause of early preterm delivery and second trimester miscarriage.

    PubMed

    Sebire, N J

    2001-04-01

    Severe preterm birth (delivery before 32 completed weeks of gestation), with or without preterm premature rupture of the membranes (PPROM), remains the leading cause of perinatal mortality. It is proposed that localized inflammation of the chorion and decidua in the membranes immediately above the internal cervical os, with or without amniotic cavity infection and inflammation, is the leading, but under recognised, cause of second trimester miscarriage and severe preterm delivery. The term 'CoDIS' (choriodecidual inflammatory syndrome), may provide a better understanding of the underlying pathophysiology than currently used terminology which over emphasizes the importance of overt intra-amniotic infection as opposed to localized extra-amniotic inflammation which stimulates uterine evacuation.

  16. Vironome of Kaposi Sarcoma associated Herpesvirus-Inflammatory Cytokine Syndrome in an AIDS patient reveals co-infection of Human Herpesvirus 8 and Human Herpesvirus 6A

    PubMed Central

    Tamburro, Kristen M.; Yang, Dongmei; Poisson, Jessica; Fedoriw, Yuri; Roy, Debasmita; Lucas, Amy; Sin, Sang-Hoon; Malouf, Nadia; Moylan, Vincent; Damania, Blossom; Moll, Stephan; van der Horst, Charles; Dittmer, Dirk P.

    2012-01-01

    KSHV inflammatory cytokine syndrome (KICS) is a newly described condition characterized by systemic illness as a result of systemic, lytic KSHV infection. We used Illumina sequencing to establish the DNA vironome of blood from such a patient. It identified concurrent high-level viremia of human herpesvirus (HHV) 8 and 6a. The HHV8 plasma viral load was 5,300,000 copies/ml, which is the highest reported to date; this despite <5 skin lesions and no HHV8 associated lymphoma. This is the first report of systemic HHV6a/KSHV co-infection in a patient. It is the first whole genome KSHV sequence to be determined directly from patient plasma rather than cultured or biopsied tumor material. This case supports KICS as a new clinical entity associated with KSHV. PMID:22925337

  17. Immune reconstitution inflammatory syndrome involving the central nervous system in a patient with HIV infection: a case report and review of literature.

    PubMed

    Zaffiri, Lorenzo; Verma, Rajanshu; Struzzieri, Kevin; Monterroso, Joanne; Batts, Donald H; Loehrke, Mark E

    2013-01-01

    IRIS is described as a paradoxical deterioration of clinical status upon initiation of combined anti-retroviral therapy (cART) in patients with HIV infection. Immune reconstitution inflammatory syndrome (CNS-IRIS) involving the central nervous system is rarely reported. We describe the case of 57-year-old man who developed a fatal case of CNS- IRIS. A rapid deterioration of neurological status was associated with progression of patchy T2-weighted hyperintensities involving different vascular territories on brain MRI. Diagnosis of CNS-IRIS is based of laboratory and radiologic findings, however brain biopsy is supportive. Despite immune restoration being involved in clinical deterioration, discontinuation of cART is not recommended. The use of corticosteroids is highly controversial. Prompt recognition of CNS-IRIS is crucial for preventing neurological complications and ensuing sequelae. PMID:23435821

  18. Xanthine Oxidase Activity Is Associated with Risk Factors for Cardiovascular Disease and Inflammatory and Oxidative Status Markers in Metabolic Syndrome: Effects of a Single Exercise Session

    PubMed Central

    Feoli, Ana Maria Pandolfo; Macagnan, Fabrício Edler; Piovesan, Carla Haas; Bodanese, Luiz Carlos; Siqueira, Ionara Rodrigues

    2014-01-01

    Objective. The main goal of the present study was to investigate the xanthine oxidase (XO) activity in metabolic syndrome in subjects submitted to a single exercise session. We also investigated parameters of oxidative and inflammatory status. Materials/Methods. A case-control study (9 healthy and 8 MS volunteers) was performed to measure XO, superoxide dismutase (SOD), glutathione peroxidase activities, lipid peroxidation, high-sensitivity C-reactive protein (hsCRP) content, glucose levels, and lipid profile. Body mass indices, abdominal circumference, systolic and diastolic blood pressure, and TG levels were also determined. The exercise session consisted of 3 minutes of stretching, 3 minutes of warm-up, 30 minutes at a constant dynamic workload at a moderate intensity, and 3 minutes at a low speed. The blood samples were collected before and 15 minutes after the exercise session. Results. Serum XO activity was higher in MS group compared to control group. SOD activity was lower in MS subjects. XO activity was correlated with SOD, abdominal circumference, body mass indices, and hsCRP. The single exercise session reduced the SOD activity in the control group. Conclusions. Our data support the association between oxidative stress and risk factors for cardiovascular diseases and suggest XO is present in the pathogenesis of metabolic syndrome. PMID:24967004

  19. Upregulated LINE-1 Activity in the Fanconi Anemia Cancer Susceptibility Syndrome Leads to Spontaneous Pro-inflammatory Cytokine Production.

    PubMed

    Brégnard, Christelle; Guerra, Jessica; Déjardin, Stéphanie; Passalacqua, Frank; Benkirane, Monsef; Laguette, Nadine

    2016-06-01

    Fanconi Anemia (FA) is a genetic disorder characterized by elevated cancer susceptibility and pro-inflammatory cytokine production. Using SLX4(FANCP) deficiency as a working model, we questioned the trigger for chronic inflammation in FA. We found that absence of SLX4 caused cytoplasmic DNA accumulation, including sequences deriving from active Long INterspersed Element-1 (LINE-1), triggering the cGAS-STING pathway to elicit interferon (IFN) expression. In agreement, absence of SLX4 leads to upregulated LINE-1 retrotransposition. Importantly, similar results were obtained with the FANCD2 upstream activator of SLX4. Furthermore, treatment of FA cells with the Tenofovir reverse transcriptase inhibitor (RTi), that prevents endogenous retrotransposition, decreased both accumulation of cytoplasmic DNA and pro-inflammatory signaling. Collectively, our data suggest a contribution of endogenous RT activities to the generation of immunogenic cytoplasmic nucleic acids responsible for inflammation in FA. The additional observation that RTi decreased pro-inflammatory cytokine production induced by DNA replication stress-inducing drugs further demonstrates the contribution of endogenous RTs to sustaining chronic inflammation. Altogether, our data open perspectives in the prevention of adverse effects of chronic inflammation in tumorigenesis. PMID:27428429

  20. Identification and Treatment of New Inflammatory Triggers for Complex Regional Pain Syndrome: Small Intestinal Bacterial Overgrowth and Obstructive Sleep Apnea.

    PubMed

    Weinstock, Leonard B; Myers, Trisha L; Walters, Arthur S; Schwartz, Oscar A; Younger, Jarred W; Chopra, Pradeep J; Guarino, Anthony H

    2016-05-01

    Complex regional pain syndrome (CRPS) is evoked by conditions that may be associated with local and/or systemic inflammation. We present a case of long-standing CRPS in a patient with Ehlers-Danlos syndrome in which prolonged remission was attained by directing therapy toward concomitant small intestinal bacterial overgrowth, obstructive sleep apnea, and potential increased microglia activity. We theorize that cytokine production produced by small intestinal bacterial overgrowth and obstructive sleep apnea may act as stimuli for ongoing CRPS symptoms. CRPS may also benefit from the properties of low-dose naltrexone that blocks microglia Toll-like receptors and induces production of endorphins that regulate and reduce inflammation. PMID:26867023

  1. [A FITZ-HUGH-CURTIS SYNDROME AS A PREMISE OF THE INFLAMMATORY DISEASES OF A HEPATOPANCREATOBILIARY ZONE ORGANS].

    PubMed

    Leonov, V V; Mayura, N A; Lyndin, M S

    2016-03-01

    A content of a biliary ways microflora and its correlation with clinical form and severity of inflammatory-destructive processes in hepatopancreatobiliary zone were studied up. The investigation objective was the optimization of a treatment--diagnostic tactics for the complications and remote recurrences rate reduction in a complicated biliary calculous disease. There was established, that a standard bacteriological investigation do not give a possibility to estimate some causes of a biliary ducts affection, a chlamidial infection in particular. So on, for the individual antibacterial therapy choosing a more detailed and modern examination of patients is needed. PMID:27514088

  2. Posterior Reversible Encephalopathy Syndrome and Fatal Cryptococcal Meningitis After Immunosuppression in a Patient With Elderly Onset Inflammatory Bowel Disease

    PubMed Central

    Vasant, Dipesh H.; Limdi, Jimmy K.; Borg-Bartolo, Simon P.; Bonington, Alec

    2016-01-01

    Advanced age and associated comorbidities are-recognized predictors of life-threatening adverse outcomes, such as opportunistic infection following immunosuppressive therapy. We describe the case of an elderly patient with stricturing colonic Crohn’s disease and significant clinical comorbidities, initially controlled with corticosteroid induction followed by infliximab, whose course was complicated by fatal disseminated cryptococcal infection and posterior reversible encephalopathy syndrome. Our patient’s case highlights rare, but serious, complications of immunosuppression. In applying modern treatment paradigms to the elderly, the clinician must consider the potential for more pronounced adverse effects in this potentially vulnerable group, maximizing benefit and minimizing harm. PMID:27807560

  3. Activation of the lectin pathway of complement by cardiopulmonary bypass contributes to the development of systemic inflammatory response syndrome after paediatric cardiac surgery.

    PubMed

    Pągowska-Klimek, I; Świerzko, A S; Michalski, M; Głowacka, E; Szala-Poździej, A; Sokołowska, A; Moll, M; Krajewski, W R; Romak, J; Cedzyński, M

    2016-05-01

    The systemic inflammatory response is a challenge in the management of paediatric patients undergoing cardiac surgery. Although multi-factorial, a contribution by the lectin pathway of complement activation has been postulated. We therefore investigated the changes in serum levels of mannose binding lectin (MBL) and activities of MBL-MBL-associated serine protease (MASP)-1 and MBL-MASP-2 complexes immediately before and during surgery, throughout the first postoperative day and at discharge from the hospital. These changes were analysed in relation to postoperative complications. Blood samples were obtained from 185 children with congenital heart disease undergoing surgical correction with the use of cardiopulmonary bypass: preoperatively (MBL-1), 15 min after initiation of cardiopulmonary bypass (CPB) (MBL-E), 30 min (MBL-2), 4 h (MBL-3), 12 h (MBL-4) and 24 h (MBL-5) post-CPB and at discharge from hospital (MBL-K). Alterations in serum MBL levels were calculated as a ratio of its serum level at subsequent time-points (MBL-2, -3, -4, -5) to the preoperative (MBL-1) value. Decreases in MBL and MBL-MASP complexes were observed in all samples, correlating with a decrease in C4 and increase in C4a, confirming activation of the lectin pathway. Changes in MBL levels between children with an uncomplicated postoperative course and those suffering from infection or low cardiac output syndrome did not differ significantly, but significant differences were observed between the SIRS and non-SIRS groups. Paediatric cardiac surgery with the use of cardiopulmonary bypass activates the complement system via the lectin pathway and the latter contributes to the development of the post-bypass systemic inflammatory response. PMID:26703090

  4. Hypoxia inducible factor-1α inhibition produced anti-allodynia effect and suppressed inflammatory cytokine production in early stage of mouse complex regional pain syndrome model.

    PubMed

    Hsiao, Hung-Tsung; Lin, Ya-Chi; Wang, Jeffrey Chi-Fei; Tsai, Yu-Chuan; Liu, Yen-Chin

    2016-03-01

    Complex regional pain syndrome (CRPS) is related to microcirculation impairment associated with tissue hypoxia and peripheral cytokine overproduction in the affected limb. Previous studies suggest that the pathogenesis involves hypoxia inducible factor-1α (HIF-1α) and exaggerated regional inflammatory response. 1-methylpropyl 2-imidazolyl disulfide (PX-12) acts as the thioredoxin-1 (Trx-1) inhibitor and decreases the level of HIF-1α, and can rapidly be metabolized for Trx-1 redox inactivation. This study hypothesized that PX-12 can decrease the cytokine production for nociceptive sensitization in the hypoxia-induced pain model. CD1 mice weighing around 30 g were used. The animal CRPS model was developed via the chronic post-ischaemic pain (CPIP) model. The model was induced by using O-rings on the ankles of the mice hind limbs to produce 3-h ischaemia-reperfusion injury on the paw. PX-12 (25 mg/kg, 5 mg/kg) was given through tail vein injection immediately after ischaemia. Animal behaviour was tested using the von Frey method for 7 days. Local paw skin tissue was harvest from three groups (control, 5 mg/kg, 25 mg/kg) 2 h after injection of PX-12. The protein expression of interleukin-1β (IL-1β) and HIF-1α was analysed with the Western blotting method. Mice significantly present an anti-allodynia effect in a dose-related manner after the PX-12 administration. Furthermore, PX-12 not only decreased the expression of HIF-1α but also decreased the expression of IL-1β over the injured palm. This study, therefore, shows the first evidence of the anti-allodynia effect of PX-12 in a CPIP animal model for pain behaviour. The study concluded that inhibition of HIF-1α may produce an analgesic effect and the associated suppression of inflammatory cytokine IL-1β in a CPIP model. PMID:26711019

  5. Systemic inflammatory response syndrome following burns is mediated by brain natriuretic peptide/natriuretic peptide A receptor-induced shock factor 1 signaling pathway.

    PubMed

    Xu, Yang-Cheng; Luo, Cheng-Qun; Li, Xiong

    2016-10-01

    The aim of this study was to determine whether systemic inflammatory response syndrome (SIRS) in burn patients is mediated by the brain natriuretic peptide (BNP)/natriuretic peptide A receptor (NPRA)-induced heat shock factor 1 (HSF-1) signalling pathway. Mononuclear cells (MNCs) that were isolated from patients with burn injuries and SIRS mouse models and a RAW264.7 cell line were treated with normal serum or serum obtained from animals with burn injuries. In parallel, small hairpin RNAs (shRNAs) against BNP or NPRA were transfected in both cell types. Western blotting (WB) and enzyme-linked immunosorbent assay (ELISA) were used to detect protein expression and inflammatory factor levels, respectively. We found that interleukin (IL)-12, tumour necrosis factor (TNF)-α, C-reactive protein (CRP), and BNP levels were increased and IL-10 levels were decreased in the plasma and MNCs in vivo in the animal model of SIRS. Additionally, NPRA was upregulated, whereas HSF-1 was downregulated in monocytes in vivo. Treatment of RAW264.7 cells with burn serum or BNP induced IL-12, TNF-α, and CRP secretion as well as HSF-1 expression. Finally, silencing BNP with shRNA interrupted the effect of burn serum on RAW264.7 cells, and silencing NPRA blocked burn serum- and BNP-mediated changes in RAW264.7 cells. These results suggest that the interaction of NPRA with BNP secreted from circulatory MNCs as well as mononuclear macrophages leads to inflammation via HSF-1 during SIRS development following serious burn injury.

  6. The exaggerated inflammatory response in Behçet's syndrome: identification of dysfunctional post-transcriptional regulation of the IFN-γ/CXCL10 IP-10 pathway.

    PubMed

    Ambrose, N; Khan, E; Ravindran, R; Lightstone, L; Abraham, S; Botto, M; Johns, M; Haskard, D O

    2015-09-01

    The mechanisms underlying the exaggerated inflammatory response in Behçet's syndrome (BS) remain poorly understood. We investigated the response of CD14(+) blood monocytes to interferon (IFN)-γ, focusing on the chemokine CXCL10. Chemokine synthesis and release were analysed at a protein and mRNA level following stimulation with IFN-γ. Findings in BS patients were compared with 25 healthy controls (HC), 15 rheumatoid arthritis (RA) and 15 systemic lupus erythematosus (SLE) disease control patients. BS monocytes produced significantly more CXCL10 protein than HC monocytes from 2 h following IFN-γ stimulation, despite equivalent quantities of mRNA, suggesting more efficient translation. This was significantly more pronounced in BS with high disease activity and in those with ocular and neurological clinical manifestations. The imbalance between CXCL10 protein and mRNA expression was not observed in either RA or SLE patients, and was not seen with other chemokines studied (CXCL9, CXCL11 and CCL2). Furthermore, BS monocytes treated with an alternative stimulant (LPS) did not show abnormal tumour necrosis factor (TNF)-α release. Sucrose density gradients to segregate monocyte CXCL10 mRNA into free RNA or polysome-associated RNA showed equal proportions in BS and HC samples, suggesting that the difference between BS and HC may be due to reduced negative control of CXCL10 translation in BS at a post-initiation level. We conclude that BS monocytes have dysfunctional post-transcriptional regulation of CXCL10 mRNA, resulting in over-expression of CXCL10 protein upon IFN-γ stimulation. As CXCL10 is a chemokine that recruits mononuclear cells, this abnormality may contribute to the exaggerated inflammatory responses that characterizes BS. PMID:25982097

  7. Anti-inflammatory effects of combined treatment with acetyl salicylic acid and atorvastatin in haemodialysis patients affected by Normal Weight Obese syndrome.

    PubMed

    Di Renzo, Laura; Noce, Annalisa; De Angelis, Sandro; Miani, Natascia; Di Daniele, Nicola; Tozzo, Carmela; De Lorenzo, Antonino

    2008-02-01

    Low-grade inflammation is a common feature of chronic kidney disease (CKD) and persistent systemic inflammation is thought to be a strong predictor of cardiovascular events. Inflammation plays a role in determining the serum albumin levels in haemodialysis patients (HD) independently of the nutritional status. Increased cardiovascular mortality in CKD has been associated with the increased incidence of obesity in uremic patients. Ingenbleek suggested a prognostic inflammation and nutritional index (PINI), based on serum albumin, pre-albumin, C-reactive protein, and alpha1 acid glycoprotein, to identify and to follow up acutely ill patients at risk of major complications. The aims of the present study were: to verify the incidence of Normal Weight Obese (NWO) syndrome; to evaluate by PINI the effect of 8 weeks acetyl salicylic (100 mg/die) and atorvastatin (10 mg/die) combined treatment on chronic inflammation in 52 selected HD patients. Laboratory evaluation, anthropometric and body composition measurements were detected. At baseline the 56.25% of non-obese, the 84.21% of pre-obese-obese, and the 41.17% of NWO women showed PINI values >1 (normal status PINI<1). After the pharmacological treatment, high significant (P<0.001) reduction in lipid profile, an elevated increase of HDL levels, and a significant reduction of inflammatory markers were obtained. Firstly, our results showed that ASA and atorvastatin combined treatment was effective in reducing inflammatory status in HD patients independently of body composition: at the end of the study only 7.49% of the patients exhibited PINI>1. Further studies will be necessary to understand the causes of inflammation in non-responder patients.

  8. Treatment and prevention of inflammatory responses and oxidative stress in patients with obstructive sleep apnea hypopnea syndrome using Chinese herbal medicines

    PubMed Central

    Chen, Qin; Lin, Rong Jing; Hong, Xuchu; Ye, Lin; Lin, Qichang

    2016-01-01

    The present study aimed to investigate the therapeutic effects of Chinese herbal medicines for the treatment and prevention of inflammatory responses and oxidative stress in obstructive sleep apnea hypopnea syndrome (OSAHS). A total of 60 patients with OSAHS were randomly divided into two groups (n=30/group): The experimental group, who received the conventional treatment + oral administration of the traditional Chinese herbal formula, Jiawei Di Tan Tang; and the control group, who received the conventional treatment only. OSAHS patients were included in the current study if they presented with snoring and had an apnea-hypopnea index (AHI) of >30 in a polysomnography study, without comorbidities. The therapeutic course lasted 12 weeks in both groups. Alterations to the mean clinical symptom score, Epworth sleepiness scale (ESS) and AHI scores, lowest nocturnal blood oxygen saturation (SaO2) and the serum levels of superoxide dismutase (SOD), malondialdehyde (MDA), interleukin (IL)-6, tumor necrosis factor (TNF)-α and C-reactive protein (CRP) prior to and following treatment were observed. The mean clinical symptom score was significantly decreased in the experimental group post-treatment compared with the control group (P<0.05). In addition, the clinical symptoms in the experimental group were significantly improved following treatment compared with pre-treatment symptoms (P<0.05). Furthermore, the ESS and AHI scores, lowest nocturnal SaO2 and serum levels of SOD, MDA, IL-6, TNF-α and CRP were significantly improved in the experimental group post-treatment compared with the control group (P<0.05). These parameters in the experimental group were also significantly improved post-treatment compared with those pre-treatment (P<0.05). The results of the present study suggested that oral administration of the traditional Chinese herbal formula Jiawei Di Tan Tang was able to attenuate oxidative stress and inflammatory responses in patients with OSAHS, and thus may

  9. An intriguing and hitherto unexplained co-occurrence: Depression and chronic fatigue syndrome are manifestations of shared inflammatory, oxidative and nitrosative (IO&NS) pathways.

    PubMed

    Maes, Michael

    2011-04-29

    There is a significant 'comorbidity' between depression and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Depressive symptoms frequently occur during the course of ME/CFS. Fatigue and somatic symptoms (F&S), like pain, muscle tension, and a flu-like malaise, are key components of depression. At the same time, depression and ME/CFS show major clinical differences, which allow to discriminate them with a 100% accuracy. This paper aims to review the shared pathways that underpin both disorders and the pathways that discriminate them. Numerous studies have shown that depression and ME/CFS are characterized by shared aberrations in inflammatory, oxidative and nitrosative (IO&NS) pathways, like systemic inflammation and its long-term sequels, including O&NS-induced damage to fatty acids, proteins and DNA; dysfunctional mitochondria; lowered antioxidant levels, like zinc and coenzyme Q10; autoimmune responses to neoepitopes formed by O&NS; lowered omega-3 polyunsaturated fatty acid levels; and increased translocation of gram-negative bacteria. Some IO&NS-related pathways, like the induction of indoleamine 2-3-dioxygenase, neurodegeneration and decreased neurogenesis, are more specific to depression, whereas other pathways, like the 2'-5' oligoadenylate synthetase/RNase L pathway, are specific to ME/CFS. Most current animal models of depression, e.g. those induced by cytokines, are not reminiscent of human depression but reflect a mixture of depressive and F&S symptoms. The latter symptoms, sometimes called sickness behavior, differ from depression and ME/CFS because the former is a (sub)acute response to infection-induced pro-inflammatory cytokines that aims to enhance recovery, whereas the latter are characterized by long-term sequels in multiple IO&NS pathways. Depression and ME/CFS are not 'comorbid' disorders, but should be regarded as 'co-associated disorders' that are clinical manifestations of shared pathways.

  10. The exaggerated inflammatory response in Behçet's syndrome: identification of dysfunctional post-transcriptional regulation of the IFN-γ/CXCL10 IP-10 pathway.

    PubMed

    Ambrose, N; Khan, E; Ravindran, R; Lightstone, L; Abraham, S; Botto, M; Johns, M; Haskard, D O

    2015-09-01

    The mechanisms underlying the exaggerated inflammatory response in Behçet's syndrome (BS) remain poorly understood. We investigated the response of CD14(+) blood monocytes to interferon (IFN)-γ, focusing on the chemokine CXCL10. Chemokine synthesis and release were analysed at a protein and mRNA level following stimulation with IFN-γ. Findings in BS patients were compared with 25 healthy controls (HC), 15 rheumatoid arthritis (RA) and 15 systemic lupus erythematosus (SLE) disease control patients. BS monocytes produced significantly more CXCL10 protein than HC monocytes from 2 h following IFN-γ stimulation, despite equivalent quantities of mRNA, suggesting more efficient translation. This was significantly more pronounced in BS with high disease activity and in those with ocular and neurological clinical manifestations. The imbalance between CXCL10 protein and mRNA expression was not observed in either RA or SLE patients, and was not seen with other chemokines studied (CXCL9, CXCL11 and CCL2). Furthermore, BS monocytes treated with an alternative stimulant (LPS) did not show abnormal tumour necrosis factor (TNF)-α release. Sucrose density gradients to segregate monocyte CXCL10 mRNA into free RNA or polysome-associated RNA showed equal proportions in BS and HC samples, suggesting that the difference between BS and HC may be due to reduced negative control of CXCL10 translation in BS at a post-initiation level. We conclude that BS monocytes have dysfunctional post-transcriptional regulation of CXCL10 mRNA, resulting in over-expression of CXCL10 protein upon IFN-γ stimulation. As CXCL10 is a chemokine that recruits mononuclear cells, this abnormality may contribute to the exaggerated inflammatory responses that characterizes BS.

  11. Citrus Polyphenol Hesperidin Stimulates Production of Nitric Oxide in Endothelial Cells while Improving Endothelial Function and Reducing Inflammatory Markers in Patients with Metabolic Syndrome

    PubMed Central

    Rizza, Stefano; Muniyappa, Ranganath; Iantorno, Micaela; Kim, Jeong-a; Chen, Hui; Pullikotil, Philomena; Senese, Nicoletta; Tesauro, Manfredi; Lauro, Davide; Cardillo, Carmine

    2011-01-01

    Context: Hesperidin, a citrus flavonoid, and its metabolite hesperetin may have vascular actions relevant to their health benefits. Molecular and physiological mechanisms of hesperetin actions are unknown. Objective: We tested whether hesperetin stimulates production of nitric oxide (NO) from vascular endothelium and evaluated endothelial function in subjects with metabolic syndrome on oral hesperidin therapy. Design, Setting, and Interventions: Cellular mechanisms of action of hesperetin were evaluated in bovine aortic endothelial cells (BAEC) in primary culture. A randomized, placebo-controlled, double-blind, crossover trial examined whether oral hesperidin administration (500 mg once daily for 3 wk) improves endothelial function in individuals with metabolic syndrome (n = 24). Main Outcome Measure: We measured the difference in brachial artery flow-mediated dilation between placebo and hesperidin treatment periods. Results: Treatment of BAEC with hesperetin acutely stimulated phosphorylation of Src, Akt, AMP kinase, and endothelial NO synthase to produce NO; this required generation of H2O2. Increased adhesion of monocytes to BAEC and expression of vascular cell adhesion molecule-1 in response to TNF-α treatment was reduced by pretreatment with hesperetin. In the clinical study, when compared with placebo, hesperidin treatment increased flow-mediated dilation (10.26 ± 1.19 vs. 7.78 ± 0.76%; P = 0.02) and reduced concentrations of circulating inflammatory biomarkers (high-sensitivity C-reactive protein, serum amyloid A protein, soluble E-selectin). Conclusions: Novel mechanisms for hesperetin action in endothelial cells inform effects of oral hesperidin treatment to improve endothelial dysfunction and reduce circulating markers of inflammation in our exploratory clinical trial. Hesperetin has vasculoprotective actions that may explain beneficial cardiovascular effects of citrus consumption. PMID:21346065

  12. Genomic and Clinical Effects Associated with a Relaxation Response Mind-Body Intervention in Patients with Irritable Bowel Syndrome and Inflammatory Bowel Disease

    PubMed Central

    Jacquart, Jolene; Scult, Matthew A.; Slipp, Lauren; Riklin, Eric Isaac Kagan; Lepoutre, Veronique; Comosa, Nicole; Norton, Beth-Ann; Dassatti, Allison; Rosenblum, Jessica; Thurler, Andrea H.; Surjanhata, Brian C.; Hasheminejad, Nicole N.; Kagan, Leslee; Slawsby, Ellen; Rao, Sowmya R.; Macklin, Eric A.; Fricchione, Gregory L.; Benson, Herbert; Libermann, Towia A.; Korzenik, Joshua; Denninger, John W.

    2015-01-01

    Introduction Irritable Bowel Syndrome (IBS) and Inflammatory Bowel Disease (IBD) can profoundly affect quality of life and are influenced by stress and resiliency. The impact of mind-body interventions (MBIs) on IBS and IBD patients has not previously been examined. Methods Nineteen IBS and 29 IBD patients were enrolled in a 9-week relaxation response based mind-body group intervention (RR-MBI), focusing on elicitation of the RR and cognitive skill building. Symptom questionnaires and inflammatory markers were assessed pre- and post-intervention, and at short-term follow-up. Peripheral blood transcriptome analysis was performed to identify genomic correlates of the RR-MBI. Results Pain Catastrophizing Scale scores improved significantly post-intervention for IBD and at short-term follow-up for IBS and IBD. Trait Anxiety scores, IBS Quality of Life, IBS Symptom Severity Index, and IBD Questionnaire scores improved significantly post-intervention and at short-term follow-up for IBS and IBD, respectively. RR-MBI altered expression of more genes in IBD (1059 genes) than in IBS (119 genes). In IBD, reduced expression of RR-MBI response genes was most significantly linked to inflammatory response, cell growth, proliferation, and oxidative stress-related pathways. In IBS, cell cycle regulation and DNA damage related gene sets were significantly upregulated after RR-MBI. Interactive network analysis of RR-affected pathways identified TNF, AKT and NF-κB as top focus molecules in IBS, while in IBD kinases (e.g. MAPK, P38 MAPK), inflammation (e.g. VEGF-C, NF-κB) and cell cycle and proliferation (e.g. UBC, APP) related genes emerged as top focus molecules. Conclusions In this uncontrolled pilot study, participation in an RR-MBI was associated with improvements in disease-specific measures, trait anxiety, and pain catastrophizing in IBS and IBD patients. Moreover, observed gene expression changes suggest that NF-κB is a target focus molecule in both IBS and IBD—and that

  13. Branched DNA-based Alu quantitative assay for cell-free plasma DNA levels in patients with sepsis or systemic inflammatory response syndrome.

    PubMed

    Hou, Yan-Qiang; Liang, Dong-Yu; Lou, Xiao-Li; Zhang, Mei; Zhang, Zhen-huan; Zhang, Lu-rong

    2016-02-01

    Cell-free circulating DNA (cf-DNA) can be detected by various of laboratory techniques. We described a branched DNA-based Alu assay for measuring cf-DNA in septic patients. Compared to healthy controls and systemic inflammatory response syndrome (SIRS) patients, serum cf-DNA levels were significantly higher in septic patients (1426.54 ± 863.79 vs 692.02 ± 703.06 and 69.66 ± 24.66 ng/mL). The areas under the receiver operating characteristic curve of cf-DNA for normal vs sepsis and SIRS vs sepsis were 0.955 (0.884-1.025), and 0.856 (0.749-0.929), respectively. There was a positive correlation between cf-DNA and interleukin 6 or procalcitonin or Acute Physiology and Chronic Health Evaluation II. The cf-DNA concentration was higher in intensive care unit nonsurviving patients compared to surviving patients (2183.33 ± 615.26 vs 972.46 ± 648.36 ng/mL; P < .05). Branched DNA-based Alu assays are feasible and useful to quantify serum cf-DNA levels. Increased cf-DNA levels in septic patients might complement C-reactive protein and procalcitonin in a multiple marker format. Cell-free circulating DNA might be a new marker in discrimination of sepsis and SIRS.

  14. A pro-inflammatory signalome is constitutively activated by C33Y mutant TNF receptor 1 in TNF receptor-associated periodic syndrome (TRAPS)

    PubMed Central

    Negm, Ola H; Mannsperger, Heiko A; McDermott, Elizabeth M; Drewe, Elizabeth; Powell, Richard J; Todd, Ian; Fairclough, Lucy C; Tighe, Patrick J

    2014-01-01

    Mutations in TNFRSF1A encoding TNF receptor 1 (TNFR1) cause the autosomal dominant TNF receptor-associated periodic syndrome (TRAPS): a systemic autoinflammatory disorder. Misfolding, intracellular aggregation, and ligand-independent signaling by mutant TNFR1 are central to disease pathophysiology. Our aim was to understand the extent of signaling pathway perturbation in TRAPS. A prototypic mutant TNFR1 (C33Y), and wild-type TNFR1 (WT), were expressed at near physiological levels in an SK-Hep-1 cell model. TNFR1-associated signaling pathway intermediates were examined in this model, and in PBMCs from C33Y TRAPS patients and healthy controls. In C33Y-TNFR1-expressing SK-Hep-1 cells and TRAPS patients’ PBMCs, a subtle, constitutive upregulation of a wide spectrum of signaling intermediates and their phosphorylated forms was observed; these were associated with a proinflammatory/antiapoptotic phenotype. In TRAPS patients’ PBMCs, this upregulation of proinflammatory signaling pathways was observed irrespective of concurrent treatment with glucocorticoids, anakinra or etanercept, and the absence of overt clinical symptoms at the time that the blood samples were taken. This study reveals the pleiotropic effect of a TRAPS-associated mutant form of TNFR1 on inflammatory signaling pathways (a proinflammatory signalome), which is consistent with the variable and limited efficacy of cytokine-blocking therapies in TRAPS. It highlights new potential target pathways for therapeutic intervention. PMID:24668260

  15. Early Electrodiagnostic Features of Upper Extremity Sensory Nerves Can Differentiate Axonal Guillain-Barré Syndrome from Acute Inflammatory Demyelinating Polyneuropathy

    PubMed Central

    Koo, Yong Seo; Shin, Ha Young; Kim, Jong Kuk; Nam, Tai-Seung; Shin, Kyong Jin; Bae, Jong-Seok; Suh, Bum Chun; Oh, Jeeyoung; Yoon, Byeol-A

    2016-01-01

    Background and Purpose Serial nerve conduction studies (NCSs) are recommended for differentiating axonal and demyelinating Guillain-Barré syndrome (GBS), but this approach is not suitable for early diagnoses. This study was designed to identify possible NCS parameters for differentiating GBS subtypes. Methods We retrospectively reviewed the medical records of 70 patients with GBS who underwent NCS within 10 days of symptom onset. Patients with axonal GBS and acute inflammatory demyelinating polyneuropathy (AIDP) were selected based on clinical characteristics and serial NCSs. An antiganglioside antibody study was used to increase the diagnostic certainty. Results The amplitudes of median and ulnar nerve sensory nerve action potentials (SNAPs) were significantly smaller in the AIDP group than in the axonal-GBS group. Classification and regression-tree analysis revealed that the distal ulnar sensory nerve SNAP amplitude was the best predictor of axonal GBS. Conclusions Early upper extremity sensory NCS findings are helpful in differentiating axonal-GBS patients with antiganglioside antibodies from AIDP patients.

  16. A CRPS-IgG-transfer-trauma model reproducing inflammatory and positive sensory signs associated with complex regional pain syndrome.

    PubMed

    Tékus, Valéria; Hajna, Zsófia; Borbély, Éva; Markovics, Adrienn; Bagoly, Teréz; Szolcsányi, János; Thompson, Victoria; Kemény, Ágnes; Helyes, Zsuzsanna; Goebel, Andreas

    2014-02-01

    The aetiology of complex regional pain syndrome (CRPS), a highly painful, usually post-traumatic condition affecting the limbs, is unknown, but recent results have suggested an autoimmune contribution. To confirm a role for pathogenic autoantibodies, we established a passive-transfer trauma model. Prior to undergoing incision of hind limb plantar skin and muscle, mice were injected either with serum IgG obtained from chronic CRPS patients or matched healthy volunteers, or with saline. Unilateral hind limb plantar skin and muscle incision was performed to induce typical, mild tissue injury. Mechanical hyperalgesia, paw swelling, heat and cold sensitivity, weight-bearing ability, locomotor activity, motor coordination, paw temperature, and body weight were investigated for 8days. After sacrifice, proinflammatory sensory neuropeptides and cytokines were measured in paw tissues. CRPS patient IgG treatment significantly increased hind limb mechanical hyperalgesia and oedema in the incised paw compared with IgG from healthy subjects or saline. Plantar incision induced a remarkable elevation of substance P immunoreactivity on day 8, which was significantly increased by CRPS-IgG. In this IgG-transfer-trauma model for CRPS, serum IgG from chronic CRPS patients induced clinical and laboratory features resembling the human disease. These results support the hypothesis that autoantibodies may contribute to the pathophysiology of CRPS, and that autoantibody-removing therapies may be effective treatments for long-standing CRPS.

  17. Positive effect of combined exercise training in a model of metabolic syndrome and menopause: autonomic, inflammatory, and oxidative stress evaluations.

    PubMed

    Conti, Filipe Fernandes; Brito, Janaina de Oliveira; Bernardes, Nathalia; Dias, Danielle da Silva; Malfitano, Christiane; Morris, Mariana; Llesuy, Susana Francisca; Irigoyen, Maria-Cláudia; De Angelis, Kátia

    2015-12-15

    It is now well established that after menopause cardiometabolic disorders become more common. Recently, resistance exercise has been recommended as a complement to aerobic (combined training, CT) for the treatment of cardiometabolic diseases. The aim of this study was to evaluate the effects of CT in hypertensive ovariectomized rats undergoing fructose overload in blood pressure variability (BPV), inflammation, and oxidative stress parameters. Female rats were divided into the following groups (n = 8/group): sedentary normotensive Wistar rats (C), and sedentary (FHO) or trained (FHOT) ovariectomized spontaneously hypertensive rats undergoing and fructose overload. CT was performed on a treadmill and ladder adapted to rats in alternate days (8 wk; 40-60% maximal capacity). Arterial pressure (AP) was directly measured. Oxidative stress and inflammation were measured on cardiac and renal tissues. The association of risk factors (hypertension + ovariectomy + fructose) promoted increase in insulin resistance, mean AP (FHO: 174 ± 4 vs. C: 108 ± 1 mmHg), heart rate (FHO: 403 ± 12 vs. C: 352 ± 11 beats/min), BPV, cardiac inflammation (tumor necrosis factor-α-FHO: 65.8 ± 9.9 vs. C: 23.3 ± 4.3 pg/mg protein), and oxidative stress cardiac and renal tissues. However, CT was able to reduce mean AP (FHOT: 158 ± 4 mmHg), heart rate (FHOT: 303 ± 5 beats/min), insulin resistance, and sympathetic modulation. Moreover, the trained rats presented increased nitric oxide bioavailability, reduced tumor necrosis factor-α (FHOT: 33.1 ± 4.9 pg/mg protein), increased IL-10 in cardiac tissue and reduced lipoperoxidation, and increased antioxidant defenses in cardiac and renal tissues. In conclusion, the association of risk factors promoted an additional impairment in metabolic, cardiovascular, autonomic, inflammatory, and oxidative stress parameters and combined exercise training was able to attenuate these dysfunctions.

  18. Age-Related Alteration of Risk Profile, Inflammatory Response, and Angiographic Findings in Patients with Acute Coronary Syndrome

    PubMed Central

    Badran, Hala Mahfouz; Elnoamany, Mohamed Fahmy; Khalil, Tarek Salah; Eldin, Mostafa Mohamed Ezz

    2009-01-01

    Background: Coronary artery disease (CAD) is a major public health problem which in turn imposes a significant burden on health care systems because of high morbidity and mortality. Although the multifactorial etiology of CAD increases with age, but in recent years, the incidence is increasing among younger age groups. Objectives: In this study we aimed to evaluate the effect of age on risk profile, inflammatory response and the angiographic findings in patients with ACS. Patients and Methods: The study comprised 253 ACS patients. Seventy six (30%) with UA, 56 (22%) with NSTEMI and 121(48%) with STEMI diagnosis. The value of Hs-CRP, lipid profile, cardiac enzymes, risk factors, EF% and angiographic score were analyzed and compared in different age groups. Results: Group 1 (n = 68) with age <45 years, group II (n = 110) with age ≥45–<65 years and group III (n = 75) ≥65 years. Group I had more prevalence of male sex, smoking, family history, hypertriglyceridemia and low levels of HDL (P < 0.01), higher incidence of STEMI (P < 0.01) and lower prevalence of UA (P < 0.01). Diabetes mellitus, hypertension, and female gender were more common in older groups. Hs-CRP was significantly lower in the young age (group I). Group I showed a preponderance of single-vessel disease, lower coronary atherosclerotic score and prevalent left anterior descending artery (LAD) involvement compared with older age groups. Hs-CRP was positively correlated to severity of CAD only in older groups. Stepwise multiple regression analysis showed that age, male gender, cardiac enzymes and EF% were common predictors of multivessel disease. Smoking was independent predictor in young patients <45 years while diabetes and Hs-CRP was the key predictor in older patient groups. Conclusion: Young patients with ACS had different clinical, angiographic and biochemical profile. Hs-CRP peak concentration did not correlate with angiographic findings in young patients that could be attributed to different

  19. Sickle erythrocytes and platelets augment lung leukotriene synthesis with downregulation of anti-inflammatory proteins: relevance in the pathology of the acute chest syndrome

    PubMed Central

    Opene, Michael; Kurantsin-Mills, Joseph; Husain, Sumair

    2014-01-01

    Abstract Initiation, progression, and resolution of vaso-occlusive pain episodes in sickle cell disease (SCD) have been recognized as reperfusion injury, which provokes an inflammatory response in the pulmonary circulation. Some 5-lipoxygenase (5-lox) metabolites are potent vasoconstrictors in the pulmonary circulation. We studied stimulation of production of the inflammatory eicosanoids leukotrienes (LTs) and prostaglandin E2 (PGE2) by isolated rat lungs perfused with sickle (HbSS) erythrocytes. Our hypothesis is that HbSS erythrocytes produce more LTs than normal (HbAA) erythrocytes, which can induce vaso-occlusive episodes in SCD patients. Lung perfusates were collected at specific time points and purified by high-pressure liquid chromatography, and LTC4 and PGE2 contents were measured by enzyme-linked immunosorbent assay (ELISA). Rat lung explants were also cultured with purified HbAA and HbSS peptides, and 5-lox, cyclooxygenase 1/2, and platelet-activating factor receptor (PAFR) proteins were measured by Western blotting, while prostacyclin and LTs produced by cultured lung explants were measured by ELISA. Lung weight gain and blood gas data were not different among the groups. HbSS-perfused lungs produced more LTC4 and PGE2 than HbAA-perfused lungs: 10.40 ± 0.62 versus 0.92 ± 0.2 ng/g dry lung weight (mean ± SEM; P = 0.0001) for LTC4. Inclusion of autologous platelets (platelet-rich plasma) elevated LTC4 production to 12.6 ± 0.96 and 7 ± 0.60 ng/g dry lung weight in HbSS and HbAA perfusates, respectively. HbSS lungs also expressed more 5-lox and PAFR. The data suggest that HbSS erythrocytes and activated platelets in patient’s pulmonary microcirculation will enhance the synthesis and release of the proinflammatory mediators LTC4 and PGE2, both of which may contribute to onset of the acute chest syndrome in SCD. PMID:25621162

  20. An Elevated Fetal IL-6 Concentration Can Be Observed In Fetuses with Anemia Due To Rh Alloimmunization: Implications for the Understanding of the Fetal Inflammatory Response Syndrome

    PubMed Central

    Vaisbuch, Edi; Romero, Roberto; Gomez, Ricardo; Kusanovic, Juan Pedro; Mazaki-Tovi, Shali; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.

    2010-01-01

    Objective The fetal inflammatory response syndrome (FIRS) has been described in the context of preterm labor and preterm PROM and is often associated with intra-amniotic infection/inflammation. This syndrome is characterized by systemic fetal inflammation and operationally-defined by an elevated fetal plasma interleukin (IL)-6. The objective of this study was to determine if FIRS can be found in fetuses with activation of their immune system, such as the one observed in Rh alloimmune-mediated fetal anemia. Methods Fetal blood sampling was performed in sensitized Rh-D negative women with suspected fetal anemia (n=16). Fetal anemia was diagnosed according to reference range nomograms established for the assessment of fetal hematologic parameters. An elevated fetal plasma IL-6 concentration was defined using a cutoff of >11 pg/mL. Concentrations of IL-6 were determined by immunoassay. Non-parametric statistics were used for analysis. Results 1) The prevalence of an elevated fetal plasma IL-6 was 25% (4/16); 2) there was an inverse relationship between the fetal hematocrit and IL-6 concentration - the lower the hematocrit, the higher the fetal IL-6 (r= −0.68, p=0.004); 3) fetuses with anemia had a significantly higher plasma IL-6 concentration than those without anemia (3.74 pg/ml, interquartile range (IQR) 1.18–2.63 vs. 1.46 pg/ml, IQR 1.76–14.7; p=0.02); 4) interestingly, all fetuses with an elevated plasma IL-6 concentration had anemia (prevalence 40%, 4/10), while in the group without anemia, none had an elevated fetal plasma IL-6. Conclusions An elevation in fetal plasma IL-6 can be observed in a subset of fetuses with anemia due to Rh alloimmunization. This observation suggests that the hallmark of FIRS can be caused by non-infection-related insults. Further studies are required to determine whether the prognosis of FIRS caused by intra-amniotic infection/inflammation is different from that induced by alloimmunization. PMID:20701435

  1. Clinical and laboratory features of overlap syndromes of idiopathic inflammatory myopathies associated with systemic lupus erythematosus, systemic sclerosis, or rheumatoid arthritis.

    PubMed

    Aguila, Lisbeth Aranbicia; Lopes, Michelle Remião Ugolini; Pretti, Flavia Zon; Sampaio-Barros, Percival Degrava; Carlos de Souza, Fernando Henrique; Borba, Eduardo Ferreira; Shinjo, Samuel Katsuyuki

    2014-08-01

    Because overlap syndromes (OSs) are rarely described, we analyzed retrospectively their frequencies and correlations in Brazilian series of 31 patients with dermatomyositis (DM)/polymyositis (PM) associated with systemic lupus erythematosus (SLE), systemic sclerosis (SSc), or rheumatoid arthritis (RA) attended at a referral single center. Myositis-specific autoantibodies (MSAs: anti-Jo-1, anti-PL-7, anti-PL-12, anti-EJ, anti-OJ, anti-SRP, anti-Mi-2) and myositis-associated autoantibodies (MAAs: anti-PM-Scl75, anti-PM-Scl100, anti-Ku) as well as specific autoantibodies related to SLE, SSc, and RA were investigated. The mean age of the OS patients (9 DM and 22 PM) was 44.6 ± 15.4 years, with a predominance of women (83.9 %) and white ethnicity (58.1 %). PM was the most frequent inflammatory myopathy, and the clinical presentation of DM/PM was significantly different among the OS groups. Overlap was found with SSc (48.4 %), SLE (29.0 %), and RA (22.6 %). The clinical manifestations of DM/PM were identified simultaneously with SSc and RA in the majority of cases, in contrast to identification in the SLE group (p < 0.05). All patients were positive for antinuclear antibodies, and the prevalence of MSA and MAA was 38.8 % in all OS groups, mutually exclusive, and more frequent in the SSc group. Comparing the clinical and laboratory features, there was a higher frequency of vascular (skin ulcers, Raynaud's phenomenon) and pulmonary (interstitial lung disease) involvement in the SSc group (p < 0.05). Moreover, there were no differences among the groups in relation to disease relapse and deaths. Concluding, this is the first study to show the different characteristics of a series of patients with connective tissue disease (CTD)-OS in the heterogeneous Brazilian population.

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

    PubMed Central

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

    2016-01-01

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

  3. Obesity with no metabolic syndrome and adipose tissue expansion based solely on risk factors and inflammatory marker of coronary heart disease in premenopausal women.

    PubMed

    Alves Ramos, Sabrina; Sabino, Adriano de Paula; Corrêa Ferreira, Daniela; Alvarez-Leite, Jacqueline Isaura

    2012-09-01

    The objective of this study was to analyze whether obese women with no metabolic syndrome (MetS) have increased cardiometabolic risk compared to non-obese women and to observe the correlations between adiposity and coronary heart disease (CHD) risk factors in metabolically healthy women. 20-40 year old non-obese (n=41), obese with no MetS (n=30) and obese with MetS (n=28) women were studied. Lipid profile, blood pressure, CHD family history, physical inactivity, high-sensitivity C-reactive protein (hs-CRP), fibrinogen, interleukin-1beta and tumor necrosis factor-alpha were analyzed. A subset of obese (13) and non-obese (33) women with no major components of MetS (except waist circumference) were further compared. Obese women with no MetS and non-obese women presented a similar metabolic profile that was statistically different from those seen in obese women with MetS. The number of obese women with no MetS and non-obese women presenting two or more risk factors (23.3 and 19.5%, respectively) or presenting high Framingham Risk Score (6.7 and 2.4%, respectively) were also similar. The only pro inflammatory protein correlated to waist circumference was hs-CRP. These data suggest that obesity with no MetS induce a CHD risk comparable to the risk seen in non-obese women. However, when women with no major components of MetS alone were considered, adiposity was positively correlated to blood pressure and hs-CRP. Although CHD risk of obese women with no MetS is closer to non-obese women, adipose tissue expansion was positively correlated to blood pressure and hs-CRP that are important risk factors for CHD.

  4. 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.

    PubMed

    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.

  5. A Prospective Follow-Up of Adipocytokines in Cohort Patients With Gout: Association With Metabolic Syndrome But Not With Clinical Inflammatory Findings

    PubMed Central

    García-Méndez, Sergio; Rivera-Bahena, Carolina Bustos; Montiel-Hernández, José Luis; Xibillé-Friedmann, Daniel; Álvarez-Hernández, Everardo; Peláez-Ballestas, Ingris; Burgos-Vargas, Rubén; Vázquez-Mellado, Janitzia

    2015-01-01

    Abstract The aim of this study was to determine the levels of leptin (Lep) and adiponectin (AdipoQ) in patients with gout and its relationship with joint inflammatory data and/or with metabolic syndrome (MetS) variables, during 1 year follow-up. Forty-one patients (40 males) with gout diagnosis, attending for the first time to a rheumatology department, were included. Evaluations were performed baseline, at 6 and 12 months. Variables included the following: demographic, clinical and laboratory data related to gout and associated diseases. Lep and AdipoQ determinations by the ELISA method were performed in frozen serum from each visit. The pharmacological and no-pharmacological treatment for gout and associated diseases was individualized for each patient according to published guidelines. Statistical analysis included Mann–Whitney U test, Fisher test, x2, ANOVA, Cochran Q, Pearson and Spearman correlation tests, as well as linear regression. In the baseline evaluation, 29.2% had MetS (hypertriglyceridemia 66%, hypertension 44% and obesity 37%); patients with MetS had higher C reactive protein (CRP) levels [34.1 ± 28.6 vs. 12.2 ± 11.2 mg/dL, P = 0.033]. Although not significant, also had higher Lep and lower AdipoQ levels (3.2 ± 3.0 vs. 1.9 ± 1.2 ng/mL, P = 0.142 and 40.5 ± 26.8 vs. 38.0 ± 24.9 ng/mL, P = 0.877, respectively). During follow-up, our patients had significant improvement in serum uric acid (sUA) levels and variables evaluating pain and joint swelling (P ≤ 0.05). Metabolic abnormalities tended to persist or even worsen during the monitoring period: significant increase in total cholesterol (P = 0.004), tendency to higher triglycerides (P = 0.883) and slight improvement in glycaemia (P = 0.052). Lep values increased significantly during follow-up (P = 0.001) while AdipoQ levels diminished slightly (P = 0.317). Neither Lep nor AdipoQ values showed important correlation (r > 0

  6. Effect of Danhong Injection Combined with Naoxintong Tablets on Prognosis and Inflammatory Factor Expression in Acute Coronary Syndrome Patients Undergoing Percutaneous Coronary Intervention

    PubMed Central

    Lv*, Yun; Pan, Yaping; Gao*, Yan; Lu, Jingqian; Li, Yi; Bai, Jie; Zhai, Jing

    2015-01-01

    Background Danhong is a Chinese medical component that has been broadly used to treat various cerebrovascular diseases. This work aimed to investigate the effect of Danhong injection combined with Naoxintong tablets on the short-term prognosis and expression of inflammatory factor-soluble CD40 ligand (sCD40L) in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). Methods A total of 100 ACS patients with PCI were randomly divided equally into treatment and control groups. The control group was treated with conventional secondary prevention of coronary heart disease. Based on secondary prevention, Danhong injection combined with Naoxintong tablets was administered in the treatment group. The incidences of major adverse cardiovascular events and cardiac functions, including ejection fraction (EF) and six-minute walk test distance, during hospital discharge and at the third postoperative month were observed. The serum sCD40 levels at different times were also noted. Results There were 2 patients in the treatment group and 7 in the control group that were lost during follow-up, so the collected data were from only 48 patients in the treatment and 43 in the control group. During hospital discharge and at the third postoperative month, no significant difference in death, myocardial infarction, stroke, angina pectoris and readmission were observed between the two groups (p > 0.05). Upon hospital discharge, EF, six-minute walk test distance and serum sCD40L level in the two groups were not significantly different (p > 0.05). At the third postoperative month, EF and six-minute walk test distance in treatment group were significantly higher than those in the control group (p < 0.05), and the serum sCD40L level in the treatment group was significantly lower than that in the control group (p < 0.01). In addition, serum sCD40L levels in the two groups at the third postoperative month were significantly lower than those during hospital

  7. Independent and opposite associations of hip and waist circumference with metabolic syndrome components and with inflammatory and atherothrombotic risk factors in overweight and obese women.

    PubMed

    Rocha, Paulo M; Barata, José T; Teixeira, Pedro J; Ross, Robert; Sardinha, Luís B

    2008-10-01

    Recent studies have shown independent and opposite associations of hip circumference (HC) and waist circumference (WC) with glucose intolerance, insulin resistance, and type 2 diabetes mellitus. However, no studies have simultaneously considered the independent contributions of both markers to metabolic proinflammatory and atherosclerotic risk factors. In this study, we examine the independent associations of WC and HC with metabolic syndrome and with proinflammatory and atherothrombotic features. Independent associations of thigh muscle and adipose tissue (AT) compartments with metabolic features were also studied. Abdominal and thigh muscle and AT distributions were assessed by computed tomography in 140 overweight and obese women (mean +/- SD: age, 38.3 +/- 0.5 years; body mass index, 30.4 +/- 0.3 kg/m(2)). Blood lipids and inflammatory and atherothrombotic markers were measured. For a given WC, a larger HC was inversely associated with fasting insulin (beta = -0.288, P = .008), hemoglobin A(1c) (beta = -0.246, P = .041), and plasminogen activator inhibitor-1 concentrations (beta = -0.241, P = .023). Contrarily, WC was related with an unfavorable metabolic profile. For a given WC, higher total thigh AT and total thigh subcutaneous AT masses were associated with lower hemoglobin A(1c) (beta = -0.244, P = .049; beta = -0.233, P = .049) and low-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (beta = -0.252, P = .040; beta = -0.245, P = .037). In addition, total thigh AT was related with leptin (beta = 0.310, P = .012), whereas total thigh subcutaneous AT revealed opposite associations with fasting insulin concentrations (beta = -0.239, P = .034). Total thigh muscular tissue mass was related with lower plasminogen activator inhibitor-1 (beta = -0.164, P = .049) and fibrinogen concentrations (beta = -0.222, P = .018). In conclusion, HC revealed independent and opposite associations with insulin resistance and atherothrombotic

  8. A Prospective Follow-Up of Adipocytokines in Cohort Patients With Gout: Association With Metabolic Syndrome But Not With Clinical Inflammatory Findings: Strobe-Compliant Article.

    PubMed

    García-Méndez, Sergio; Rivera-Bahena, Carolina Bustos; Montiel-Hernández, José Luis; Xibillé-Friedmann, Daniel; Álvarez-Hernández, Everardo; Peláez-Ballestas, Ingris; Burgos-Vargas, Rubén; Vázquez-Mellado, Janitzia

    2015-07-01

    The aim of this study was to determine the levels of leptin (Lep) and adiponectin (AdipoQ) in patients with gout and its relationship with joint inflammatory data and/or with metabolic syndrome (MetS) variables, during 1 year follow-up.Forty-one patients (40 males) with gout diagnosis, attending for the first time to a rheumatology department, were included. Evaluations were performed baseline, at 6 and 12 months. Variables included the following: demographic, clinical and laboratory data related to gout and associated diseases. Lep and AdipoQ determinations by the ELISA method were performed in frozen serum from each visit. The pharmacological and no-pharmacological treatment for gout and associated diseases was individualized for each patient according to published guidelines. Statistical analysis included Mann-Whitney U test, Fisher test, x, ANOVA, Cochran Q, Pearson and Spearman correlation tests, as well as linear regression.In the baseline evaluation, 29.2% had MetS (hypertriglyceridemia 66%, hypertension 44% and obesity 37%); patients with MetS had higher C reactive protein (CRP) levels [34.1 ± 28.6 vs. 12.2 ± 11.2 mg/dL, P = 0.033]. Although not significant, also had higher Lep and lower AdipoQ levels (3.2 ± 3.0 vs. 1.9 ± 1.2 ng/mL, P = 0.142 and 40.5 ± 26.8 vs. 38.0 ± 24.9 ng/mL, P = 0.877, respectively). During follow-up, our patients had significant improvement in serum uric acid (sUA) levels and variables evaluating pain and joint swelling (P ≤ 0.05). Metabolic abnormalities tended to persist or even worsen during the monitoring period: significant increase in total cholesterol (P = 0.004), tendency to higher triglycerides (P = 0.883) and slight improvement in glycaemia (P = 0.052). Lep values increased significantly during follow-up (P = 0.001) while AdipoQ levels diminished slightly (P = 0.317). Neither Lep nor AdipoQ values showed important correlation (r > 0.5) with metabolic variables or joint swelling.This study suggests that in patients

  9. Enhancing of Women Functional Status with Metabolic Syndrome by Cardioprotective and Anti-Inflammatory Effects of Combined Aerobic and Resistance Training

    PubMed Central

    Alsamir Tibana, Ramires; da Cunha Nascimento, Dahan; Frade de Sousa, Nuno Manuel; de Souza, Vinicius Carolino; Durigan, João; Vieira, Amilton; Bottaro, Martim; de Toledo Nóbrega, Otávio; de Almeida, Jeeser Alves; Navalta, James Wilfred; Franco, Octavio Luiz; Prestes, Jonato

    2014-01-01

    These data describe the effects of combined aerobic plus resistance training (CT) with regards to risk factors of metabolic syndrome (MetS), quality of life, functional capacity, and pro- and anti-inflammatory cytokines in women with MetS. In this context, thirteen women (35.4±6.2 yr) completed 10 weeks of CT consisting of three weekly sessions of ∼60 min aerobic training (treadmill at 65–70% of reserve heart rate, 30 min) and resistance training (3 sets of 8–12 repetitions maximum for main muscle groups). Dependent variables were maximum chest press strength; isometric hand-grip strength; 30 s chair stand test; six minute walk test; body mass; body mass index; body adiposity index; waist circumference; systolic (SBP), diastolic and mean blood pressure (MBP); blood glucose; HDL-C; triglycerides; interleukins (IL) 6, 10 and 12, osteoprotegerin (OPG) and serum nitric oxide metabolite (NOx); quality of life (SF-36) and Z-Score of MetS. There was an improvement in muscle strength on chest press (p = 0.009), isometric hand-grip strength (p = 0.03) and 30 s chair stand (p = 0.007). There was a decrease in SBP (p = 0.049), MBP (p = 0.041), Z-Score of MetS (p = 0.046), OPG (0.42±0.26 to 0.38±0.19 ng/mL, p<0.05) and NOx (13.3±2.3 µmol/L to 9.1±2.3 µmol/L; p<0.0005). IL-10 displayed an increase (13.6±7.5 to 17.2±12.3 pg/mL, p<0.05) after 10 weeks of training. Combined training also increased the perception of physical capacity (p = 0.011). This study endorses CT as an efficient tool to improve blood pressure, functional capacity, quality of life and reduce blood markers of inflammation, which has a clinical relevance in the prevention and treatment of MetS. Trial Registration Brazilian Clinical Trials Registry (ReBec) - RBR-6gdyvz - http://www.ensaiosclinicos.gov.br/rg/?q=RBR-6gdyvz PMID:25379699

  10. Ocular manifestations of systemic inflammatory diseases.

    PubMed

    Mohsenin, Amir; Huang, John J

    2012-10-01

    Inflammation of the eye is often times seen in association with systemic inflammatory diseases. Understanding the various forms of ocular involvement in these conditions is important as untreated ophthalmic involvement can lead to severe vision loss. In addition to providing a basic framework for diagnosis and treatment, this review will highlight the ocular manifestations of the following systemic inflammatory conditions: rheumatoid arthritis, systemic lupus erythematosus, Wegener's granulomatosis, Sjögren's syndrome, polyarteritisnodosa, primary antiphospholipid syndrome, Behçet's syndrome, Kawasaki disease, Cogan's syndrome and relapsing polychondritis.

  11. Dynamics of Adrenal Steroids Are Related to Variations in Th1 and Treg Populations during Mycobacterium tuberculosis Infection in HIV Positive Persons

    PubMed Central

    Quiroga, Maria Florencia; Angerami, Matias Tomas; Santucci, Natalia; Ameri, Diego; Francos, Jose Luis; Wallach, Jorge; Sued, Omar; Cahn, Pedro; Salomón, Horacio; Bottasso, Oscar

    2012-01-01

    Tuberculosis (TB) remains the most frequent cause of illness and death from an infectious agent, and its interaction with HIV has devastating effects. We determined plasma levels of dehydroepiandrosterone (DHEA), its circulating form DHEA-suphate (DHEA-s) and cortisol in different stages of M. tuberculosis infection, and explored their role on the Th1 and Treg populations during different scenarios of HIV-TB coinfection, including the immune reconstitution inflammatory syndrome (IRIS), a condition related to antiretroviral treatment. DHEA levels were diminished in HIV-TB and HIV-TB IRIS patients compared to healthy donors (HD), HIV+ individuals and HIV+ individuals with latent TB (HIV-LTB), whereas dehydroepiandrosterone sulfate (DHEA-s) levels were markedly diminished in HIV-TB IRIS individuals. HIV-TB and IRIS patients presented a cortisol/DHEA ratio significantly higher than HIV+, HIV-LTB and HD individuals. A positive correlation was observed between DHEA-s and CD4 count among HIV-TB individuals. Conversely, cortisol plasma level inversely correlated with CD4 count within HIV-TB individuals. M. tuberculosis-specific Th1 lymphocyte count was increased after culturing PBMC from HIV-TB individuals in presence of DHEA. We observed an inverse correlation between DHEA-s plasma level and Treg frequency in co-infected individuals, and CD4+FoxP3+ Treg frequency was increased in HIV-TB and IRIS patients compared to other groups. Strikingly, we observed a prominent CD4+CD25-FoxP3+ population across HIV-TB and HIV-TB IRIS patients, which frequency correlated with DHEA plasma level. Finally, DHEA treatment negatively regulated FoxP3 expression without altering Treg frequency in co-infected patients. These data suggest an enhancing role for DHEA in the immune response against M. tuberculosis during HIV-TB coinfection and IRIS. PMID:22431997

  12. Idiopathic Inflammatory Myopathies

    PubMed Central

    Dimachkie, Mazen M.; Barohn, Richard J.

    2012-01-01

    The idiopathic inflammatory myopathies are a group of rare disorders including polymyositis (PM), dermatomyositis (DM), and autoimmune necrotizing myopathies (NMs). The idiopathic inflammatory myopathies share many similarities. They present acutely, subacutely, or chronically with marked proximal and symmetric muscle weakness, except for associated distal and asymmetric weakness in inclusion body myositis. The idiopathic inflammatory myopathies also share a variable degree of creatine kinase (CK) elevation and a nonspecifically abnormal electromyogram demonstrating an irritative myopathy. The muscle pathology demonstrates inflammatory exudates of variable distribution within the muscle fascicle. Despite these similarities, the idiopathic inflammatory myopathies are a heterogeneous group. The overlap syndrome (OS) refers to the association of PM, DM, or NM with connective tissue disease, such as scleroderma or systemic lupus erythematosus. In addition to elevated antinuclear antibodies (ANA), patients with OS may be weaker in the proximal arms than the legs mimicking the pattern seen in some muscular dystrophies. In this review, we focus on DM, PM, and NM and examine current and promising therapies. PMID:23117947

  13. Idiopathic inflammatory myopathies.

    PubMed

    Dimachkie, Mazen M; Barohn, Richard J

    2012-07-01

    The idiopathic inflammatory myopathies are a group of rare disorders including polymyositis (PM), dermatomyositis (DM), and autoimmune necrotizing myopathies (NMs). The idiopathic inflammatory myopathies share many similarities. They present acutely, subacutely, or chronically with marked proximal and symmetric muscle weakness, except for associated distal and asymmetric weakness in inclusion body myositis. The idiopathic inflammatory myopathies also share a variable degree of creatine kinase (CK) elevation and a nonspecifically abnormal electromyogram demonstrating an irritative myopathy. The muscle pathology demonstrates inflammatory exudates of variable distribution within the muscle fascicle. Despite these similarities, the idiopathic inflammatory myopathies are a heterogeneous group. The overlap syndrome (OS) refers to the association of PM, DM, or NM with connective tissue disease, such as scleroderma or systemic lupus erythematosus. In addition to elevated antinuclear antibodies (ANA), patients with OS may be weaker in the proximal arms than the legs mimicking the pattern seen in some muscular dystrophies. In this review, we focus on DM, PM, and NM and examine current and promising therapies.

  14. Allergic acute coronary syndrome (Kounis syndrome)

    PubMed Central

    Chhabra, Lovely; Masrur, Shihab; Parker, Matthew W.

    2015-01-01

    Anaphylaxis rarely manifests as a vasospastic acute coronary syndrome with or without the presence of underlying coronary artery disease. The variability in the underlying pathogenesis produces a wide clinical spectrum of this syndrome. We present three cases of anaphylactic acute coronary syndrome that display different clinical variants of this phenomenon. The main pathophysiological mechanism of the allergic anginal syndromes is the inflammatory mediators released during a hypersensitivity reaction triggered by food, insect bites, or drugs. It is important to appropriately recognize and treat Kounis syndrome in patients with exposure to a documented allergen. PMID:26130889

  15. Inflammatory biomarkers CRP, MCP-1, serum amyloid alpha and interleukin-18 in patients with HTN and dyslipidemia: impact of diabetes mellitus on metabolic syndrome and the effect of statin therapy.

    PubMed

    Rabkin, Simon W; Langer, Anatoly; Ur, Ehud; Calciu, Cristina-Dana; Leiter, Lawrence A

    2013-06-01

    The objective of this study was to determine the relationship of HTN (HTN) and the inflammatory markers C-reactive protein (CRP), monocyte chemoattractant protein-1 (MCP-1), amyloid alpha (AA) and interleukin-18 (IL-18) in persons with HTN, considering concomitant diabetes mellitus (DM) or metabolic syndrome (MS). This was a multicenter twelve-week, single-step titration, open-label study of individuals with dyslipidemia, assigned according to their initial risk assessment, to atorvastatin starting doses of 10, 20, 40 or 80 mg. In subjects with HTN (N=677) versus no HTN (N=581), there were significantly (P<0.02) higher levels of CRP, IL-18, MCP-1 and AA but not for IL-18 when combined with DM or MS, and AA or CRP when combined with MS. Systolic blood pressure significantly (P<0.02) correlated with CRP, MCP-1 and AA but not IL-18. The greatest increase in CRP was with HTN plus DM. Statin therapy produced significant dose-dependent reductions in CRP but not with similar changes in other inflammatory markers. In summary, these data suggest a complex relationship between inflammation and HTN with dyslipidemia. Although HTN is associated with an increase in these inflammatory markers, the associated conditions DM or MS lead to different patterns of increases-MCP-1 being the most consistently increased with HTN, the greatest CRP increase was with HTN and DM, and no relationship was found with IL-18 and HTN in the presence of DM or MS. In addition, there are different responses to statins depending on the nature of the inflammatory marker.

  16. Blind loop syndrome

    MedlinePlus

    ... operations for extreme obesity As a complication of inflammatory bowel disease Diseases such as diabetes or scleroderma may slow down movement in a segment of the intestine, leading to blind loop syndrome.

  17. Why myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) may kill you: disorders in the inflammatory and oxidative and nitrosative stress (IO&NS) pathways may explain cardiovascular disorders in ME/CFS.

    PubMed

    Maes, Michael; Twisk, Frank Nm

    2009-01-01

    There is evidence that disorders in inflammatory and oxidative and nitrosative (IO&NS) pathways and a lowered antioxidant status are important pathophysiological mechanisms underpinning myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS). Important precipitating and perpetuating factors for ME/CFS are (amongst others) bacterial and viral infections; bacterial translocation due to an increased gut permeability; and psychological stress. Recently, Jason et al (2006) reported that the mean age of patients with myalgic encephalomyelitis/chronic fatigue syndrome dying from heart failure, i.e. 58.7 years, is significantly lower than the age of those dying from heart failure in the general US population, i.e. 83.1 years. These findings implicate that ME/CFS is a risk factor to cardio-vascular disorder. This review demonstrates that disorders in various IO&NS pathways provide explanations for the earlier mortality due to cardiovascular disorders in ME/CFS. These pathways are: a) chronic low grade inflammation with extended production of nuclear factor kappa B and COX-2 and increased levels of tumour necrosis factor alpha; b) increased O&NS with increased peroxide levels, and phospholipid oxidation including oxidative damage to phosphatidylinositol; c) decreased levels of specific antioxidants, i.e. coenzyme Q10, zinc and dehydroepiandrosterone-sulphate; d) bacterial translocation as a result of leaky gut; e) decreased omega-3 polyunsatutared fatty acids (PUFAs), and increased omega-6 PUFA and saturated fatty acid levels; and f) the presence of viral and bacterial infections and psychological stressors. The mechanisms whereby each of these factors may contribute towards cardio-vascular disorder in ME/CFS are discussed. ME/CFS is a multisystemic metabolic-inflammatory disorder. The aberrations in IO&NS pathways may increase the risk for cardiovascular disorders.

  18. Plasma Inflammatory Cytokine IL-4, IL-8, IL-10, and TNF-α Levels Correlate with Pulmonary Function in Patients with Asthma-Chronic Obstructive Pulmonary Disease (COPD) Overlap Syndrome.

    PubMed

    Huang, Ai-Xia; Lu, Li-Wen; Liu, Wen-Juan; Huang, Mao

    2016-01-01

    BACKGROUND The aim of this study was to investigate the plasma inflammatory cytokine levels and their correlations with pulmonary function in patients with asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS). MATERIAL AND METHODS Between January 2013 and December 2014, a total of 96 patients with asthma, acute exacerbation of chronic obstructive pulmonary disease (AECOPD), or ACOS were enrolled, and 35 healthy people were included as a control group. Fasting plasma interleukin (IL)-4, IL-8, IL-10, and tumor necrosis factor alpha (TNF-α) levels were detected using enzyme-linked immunosorbent assay (ELISA). Correlations between the plasma inflammatory cytokine levels and forced expiratory volume in 1 second (FEV1), FEV1/predicted value ratio (FEV1%pred), and FEV1/forced vital capacity (FVC) were analyzed. RESULTS IL-4 and IL-8 levels showed statistically significant differences among the 3 groups of patients (both P<0.001); IL-4 level was significantly lower, while IL-8 level was significantly higher in the AECOPD group and ACOS group than those in the asthma group (all P<0.05). IL-10 level and TNF-α level were significantly different among the 3 patient groups (both P<0.001). IL-10 level was significantly different between each of the 2 groups (all P<0.001). TNF-α level in the asthma group was higher than in the AECOPD group and ACOS group (both P<0.001). IL-4 and IL-10 were positively and IL-8 and TNF-α were negatively related with FEV1, FEV1%pred, and FEV1/FVC. CONCLUSIONS Plasma levels of inflammatory cytokines IL-4, IL-8, IL-10, and TNF-α are related with severity of airway diseases and could be potential markers for the evaluation of asthma, COPD, and ACOS.

  19. Effect of amino acids residues 323-433 and 628-747 in Nsp2 of representative porcine reproductive and respiratory syndrome virus strains on inflammatory response in vitro.

    PubMed

    Liu, Xing; Bai, Juan; Wang, Haiyan; Fan, Baochao; Li, Yufeng; Jiang, Ping

    2015-10-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) is an important pathogen that is responsible for large economic losses in the swine industry worldwide. In PRRSV strains, many genetic variations occur in the central hypervariable region (HV2) of the Nsp2 gene, which encodes non-structural protein 2. For example, PRRSV strains VR2332, Em2007, MN184C, and TJM-F92 contained variations in the Nsp2 sequences and exhibited differing levels of virulence in adult pigs. However, the role of HV2 with respect to PRRSV immunity is unclear. In this study, four recombinant PRRSV strains (rBB/+30aa, rBB/Δ68aa, rBB/Δ111aa, and rBB/Δ120aa) were rescued using a highly pathogenic type 2 PRRSV cDNA clone (pBB). All rescued strains displayed similar growth characteristics to the parental rBB virus in pulmonary alveolar macrophages (PAMs). Expression levels of inflammatory cytokines IL-β, IL-6, and TNF-α were significantly lower, at the mRNA and protein level, for groups infected with rBB/Δ111aa and rBB/Δ120aa than those in the rBB group. Levels of these inflammatory cytokines in the rBB/+30aa and rBB/Δ68aa groups were not significantly different with those in the rBB group. Phosphorylation levels of IκB were decreased to a greater extent in the rBB/Δ111aa and rBB/Δ120aa groups compared with those in the rBB/+30aa, rBB/Δ68aa, and rBB groups. Our results indicate that amino acids 323-433 and 628-747 of Nsp2 failed to exert significant effects on PRRSV replication in PAMs, but modulated the expression of inflammatory cytokines in vitro.

  20. Plasma Inflammatory Cytokine IL-4, IL-8, IL-10, and TNF-α Levels Correlate with Pulmonary Function in Patients with Asthma-Chronic Obstructive Pulmonary Disease (COPD) Overlap Syndrome

    PubMed Central

    Huang, Ai-Xia; Lu, Li-Wen; Liu, Wen-Juan; Huang, Mao

    2016-01-01

    Background The aim of this study was to investigate the plasma inflammatory cytokine levels and their correlations with pulmonary function in patients with asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS). Material/Methods Between January 2013 and December 2014, a total of 96 patients with asthma, acute exacerbation of chronic obstructive pulmonary disease (AECOPD), or ACOS were enrolled, and 35 healthy people were included as a control group. Fasting plasma interleukin (IL)-4, IL-8, IL-10, and tumor necrosis factor alpha (TNF-α) levels were detected using enzyme-linked immunosorbent assay (ELISA). Correlations between the plasma inflammatory cytokine levels and forced expiratory volume in 1 second (FEV1), FEV1/predicted value ratio (FEV1%pred), and FEV1/forced vital capacity (FVC) were analyzed. Results IL-4 and IL-8 levels showed statistically significant differences among the 3 groups of patients (both P<0.001); IL-4 level was significantly lower, while IL-8 level was significantly higher in the AECOPD group and ACOS group than those in the asthma group (all P<0.05). IL-10 level and TNF-α level were significantly different among the 3 patient groups (both P<0.001). IL-10 level was significantly different between each of the 2 groups (all P<0.001). TNF-α level in the asthma group was higher than in the AECOPD group and ACOS group (both P<0.001). IL-4 and IL-10 were positively and IL-8 and TNF-α were negatively related with FEV1, FEV1%pred, and FEV1/FVC. Conclusions Plasma levels of inflammatory cytokines IL-4, IL-8, IL-10, and TNF-α are related with severity of airway diseases and could be potential markers for the evaluation of asthma, COPD, and ACOS. PMID:27501772

  1. Ischemic heart disease in systemic inflammatory diseases. An appraisal.

    PubMed

    Gargiulo, Paola; Marsico, Fabio; Parente, Antonio; Paolillo, Stefania; Cecere, Milena; Casaretti, Laura; Pellegrino, Angela Maria; Formisano, Tiziana; Fabiani, Irma; Soricelli, Andrea; Trimarco, Bruno; Perrone-Filardi, Pasquale

    2014-01-01

    Systemic inflammatory diseases are inflammatory syndromes that are associated with increased cardiovascular morbidity and mortality. The link between inflammatory and cardiovascular diseases can be attributed to coexistence of classical risk factors and of inflammatory mechanisms activated in systemic inflammatory diseases and involving the immune system. Yet, clinical implications of these findings are not entirely clear and deeper knowledge and awareness of cardiac involvement in inflammatory diseases are necessary. The aims of this review are to summarize cardiac involvement in systemic inflammatory diseases and to identify areas where evidence is currently lacking that deserve further investigation in the future.

  2. Inflammatory mediators in acute pancreatitis.

    PubMed

    Bhatia, M; Brady, M; Shokuhi, S; Christmas, S; Neoptolemos, J P; Slavin, J

    2000-02-01

    Inflammatory mediators play a key role in acute pancreatitis and the resultant multiple organ dysfunction syndrome, which is the primary cause of death in this condition. Recent studies have confirmed the critical role played by inflammatory mediators such as TNF-alpha, IL-1beta, IL-6, IL-8, PAF, IL-10, C5a, ICAM-1, and substance P. The systemic effects of acute pancreatitis have many similarities to those of other conditions such as septicaemia, severe burns, and trauma. The delay between the onset of inflammation in the pancreas and the development of the systemic response makes acute pancreatitis an ideal experimental and clinical model with which to study the role of inflammatory mediators and to test novel therapies. Elucidation of the key mediators involved in the pathogenesis of acute pancreatitis will facilitate the development of clinically effective anti-inflammatory therapy.

  3. Effects of angiotensin-converting enzyme inhibitor therapy on levels of inflammatory markers in response to exercise-induced stress: studies in the metabolic syndrome.

    PubMed

    Vaccari, Christopher S; Rahman, Syed T; Khan, Qamar A; Cheema, Faiz A; Khan, Bobby V

    2008-01-01

    The authors sought to determine whether the angiotensin-converting enzyme (ACE) inhibitor perindopril has beneficial effects on vascular markers of inflammation in patients with the metabolic syndrome when exposed to exercise-induced stress. Thirty patients with the metabolic syndrome were randomized to perindopril (4 mg/d) or placebo in a double-blind fashion for 4 weeks. Prior to treatment, the patients underwent an exercise treadmill study to a level of 8 metabolic equivalents. Circulating monocyte CD11b expression, levels of soluble interleukin 6 (sIL-6), and levels of vascular cell adhesion molecule-1 (VCAM-1) were measured. After the treatment period, exercise treadmill study and measurement of markers were repeated. Treatment with perindopril reduced sIL-6 levels at pre-exercise by 22% and at 1 and 30 minutes by 30% and 33%, respectively (P<.005). Levels of soluble VCAM-1 in perindopril-treated patients were reduced at pre-exercise by 25% and at 1 and 30 minutes by 31% and 37%, respectively. Treatment with perindopril reduced monocyte CD11b expression by 25%. In response to exercise-induced physical stress, the addition of an ACE inhibitor differentially regulates markers of inflammation, thereby providing potential vascular protection in the metabolic syndrome.

  4. Inflammatory Myopathies.

    PubMed

    Atluri, Rama Bandlamudi

    2016-01-01

    Idiopathic inflammatory myopathies are relatively rare diseases. Polymyositis and dermatomyositis are more common in women than men (2:1 ratio), while inclusion body myositis is twice as common in men. Inflammatory myopathies are a heterogeneous group of chronic systemic autoimmune diseases with an annual incidence of two to five cases per million, characterized by muscle inflammation and progressive muscle weakness. There are three major diseases which includes Dermatomyositis (DM) including a distinct juvenile subtype (JDM), Polymyositis (PM), and Inclusion Body Myositis. DM is a compliment mediated microangiopathy affecting skin and muscle. PM and IBM are T-cell mediated disorders, where CD8 positive cytotoxic T cells invade muscle fibers expressing MHC class I antigens, this leading to fiber necrosis. In IBM, vacuolar formation with amyloid deposits are also present. This article summarizes the clinical, histochemical and immunological features as well as the treatment options of the inflammatory myopathies. PMID:27311223

  5. Comparison of serum levels of inflammatory markers in patients with coronary vasospasm without significant fixed coronary artery disease versus patients with stable angina pectoris and acute coronary syndromes with significant fixed coronary artery disease.

    PubMed

    Hung, Ming-Jui; Cherng, Wen-Jin; Cheng, Chi-Wen; Li, Li-Fu

    2006-05-15

    Serum levels of inflammatory markers (interleukin-6, monocyte chemoattractant protein-1, soluble intercellular adhesion molecule-1, soluble vascular adhesion molecule-1, and C-reactive protein) were measured at baseline in serum samples from 189 patients who were admitted for coronary angiography because of suspected ischemic heart disease. Median duration of follow-up was 28 months. Patients in our sample were enrolled in 4 diagnostic groups: no hemodynamically significant coronary artery disease (CAD) and no coronary vasospasm (control group, n = 32), hemodynamically significant CAD and stable angina pectoris (SAP group, n = 34), coronary vasospastic angina pectoris without hemodynamically significant CAD (vasospasm group, n = 31), and acute coronary syndrome (ACS) and hemodynamically significant CAD (ACS group, n = 92). Overall, the level of serum inflammatory markers was highest in the ACS group and lowest in the control group, with intermediate values observed in the SAP and vasospasm groups, with the exception of soluble intercellular adhesion molecule-1, the level of which was highest in the vasospasm group. Multivariate analysis showed that log (interleukin-6) was independently associated with a diagnosis of coronary vasospastic angina pectoris in patients without hemodynamically significant CAD (odds ratio 8.48, p = 0.027). Patients in the ACS group had a significantly lower survival rate compared with the other 3 groups but without an independent predictor that could be identified in this patient cohort. Recurrent angina pectoris occurred with similar rates in the SAP, vasospasm, and ACS groups. The independent predictor for recurrent angina pectoris was treatment that did not include clopidogrel (odds ratio 3.88, p = 0.007). In conclusion, the results of this study suggest that inflammation can exist in coronary vasospasm without hemodynamically significant CAD.

  6. The Interferon-Signature of Sjögren’s Syndrome: How Unique Biomarkers Can Identify Underlying Inflammatory and Immunopathological Mechanisms of Specific Diseases

    PubMed Central

    Nguyen, Cuong Quoc; Peck, Ammon Broughton

    2013-01-01

    Innate immune responses direct the nature and specificity of downstream adaptive responses in autoimmune diseases. One of the strongest markers of innate immunity is the up-regulated expression of interferon (IFN) and IFN-responsive/stimulated genes (IRGs/ISGs). While multiple IRGs are induced during the innate phase of host responses, transcriptome data suggest unique IRG-signatures for different diseases. Sjögren’s syndrome (SjS) is characterized by chronic immune attacks against exocrine glands leading to exocrine dysfunction, plus strong up-regulated expressions of IFN IRG transcripts. Genome-wide transcriptome analyses indicate that differentially expressed IRGs are restricted during disease development and therefore define underlying etiopathological mechanisms. Here we review the innate immune-associated IFN-signature of SjS and show how differential gene expressions of IRG/ISG sets interact molecularly and biologically to identify critical details of SjS etiopathogenesis. PMID:23847613

  7. 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.

    PubMed

    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).

  8. Other noninfectious inflammatory disorders.

    PubMed

    Rovira, Álex; Auger, Cristina; Rovira, Antoni

    2016-01-01

    Idiopathic inflammatory-demyelinating diseases (IIDDs) represent a broad spectrum of central nervous system (CNS) disorders, including monophasic, multiphasic, and progressive disorders that range from highly localized forms to multifocal or diffuse variants. In addition to the classic multiple sclerosis (MS) phenotypes, several MS variants have been described, which can be differentiated on the basis of severity, clinical course, and lesion distribution. Other forms of IIDD are now recognized as distinct entities and not MS variants, such as acute disseminated encephalomyelitis, and neuromyelitis optica spectrum disorders. The CNS can also be affected by a variety of inflammatory diseases. These include primary angiitis of the CNS (PACNS), a rare disorder specifically targeting the CNS vasculature, and various systemic conditions which, among other organs and systems, can also affect the CNS, such as systemic vasculitis and sarcoidosis. The diagnosis of PACNS is difficult, as this condition may be confused with reversible cerebral vasoconstriction syndrome (RCVS), a term comprising a group of conditions characterized by prolonged but reversible vasoconstriction of the cerebral arteries. Magnetic resonance imaging of the brain and spine is the radiologic technique of choice for diagnosing these disorders, and, together with the clinical and laboratory findings, enables a prompt and accurate diagnosis. PMID:27432677

  9. CANDLE syndrome: a recently described autoinflammatory syndrome.

    PubMed

    Tüfekçi, Özlem; Bengoa, ŞebnemYilmaz; Karapinar, Tuba Hilkay; Ataseven, Eda Büke; İrken, Gülersu; Ören, Hale

    2015-05-01

    CANDLE syndrome (chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature) is a recently described autoinflammatory syndrome characterized by early onset, recurrent fever, skin lesions, and multisystemic inflammatory manifestations. Most of the patients have been shown to have mutation in PSMB8 gene. Herein, we report a 2-year-old patient with young onset recurrent fever, atypical facies, widespread skin lesions, generalized lymphadenopathy, hepatosplenomegaly, joint contractures, hypertrglyceridemia, lipodystrophy, and autoimmune hemolytic anemia. Clinical features together with the skin biopsy findings were consistent with the CANDLE syndrome. The pathogenesis and treatment of this syndrome have not been fully understood. Increased awareness of this recently described syndrome may lead to recognition of new cases and better understanding of its pathogenesis which in turn may help for development of an effective treatment. PMID:25036278

  10. Anti-inflammatory actions of acupuncture.

    PubMed Central

    Zijlstra, Freek J; van den Berg-de Lange, Ineke; Huygen, Frank J P M; Klein, Jan

    2003-01-01

    Acupuncture has a beneficial effect when treating many diseases and painful conditions, and therefore is thought to be useful as a complementary therapy or to replace generally accepted pharmacological intervention. The attributive effect of acupuncture has been investigated in inflammatory diseases, including asthma, rhinitis, inflammatory bowel disease, rheumatoid arthritis, epicondylitis, complex regional pain syndrome type 1 and vasculitis. Large randomised trials demonstrating the immediate and sustained effect of acupuncture are missing. Mechanisms underlying the ascribed immunosuppressive actions of acupuncture are reviewed in this communication. The acupuncture-controlled release of neuropeptides from nerve endings and subsequent vasodilative and anti-inflammatory effects through calcitonine gene-related peptide is hypothesised. The complex interactions with substance P, the analgesic contribution of beta-endorphin and the balance between cell-specific pro-inflammatory and anti-inflammatory cytokines tumour necrosis factor-alpha and interleukin-10 are discussed. PMID:12775355

  11. A Randomized, Double-Blind, Placebo-Controlled Clinical Trial of a Chemokine Receptor 5 (CCR5) Antagonist to Decrease the Occurrence of Immune Reconstitution Inflammatory Syndrome in HIV-Infection: The CADIRIS Study

    PubMed Central

    Sierra-Madero, Juan G.; Ellenberg, Susan; Rassool, Mohammed S.; Tierney, Ann; Belaunzarán-Zamudio, Pablo F.; López-Martínez, Alondra; Piñeirúa-Menéndez, Alicia; Montaner, Luis J.; Azzoni, Livio; Benítez, César Rivera; Sereti, Irini; Andrade-Villanueva, Jaime; Mosqueda-Gómez, Juan L.; Rodriguez, Benigno; Sanne, Ian; Lederman, Michael M.

    2015-01-01

    Background Immune Reconstitution Inflammatory Syndrome (IRIS) is a common complication of antiretroviral therapy (ART) in HIV-infected patients. IRIS is associated with an increased risk of hospitalization and death. We ascertained whether CCR5 blockade using maraviroc reduces the risk of IRIS. Methods The CADIRIS study was a randomized, double-blind, placebo-controlled, clinical trial that accrued subjects from five clinical sites in Mexico and one in South Africa between November 2009 and January 2012, and followed them for one year. The primary outcome was occurrence of IRIS by 24 weeks. HIV-infected adults, naïve to ART, with CD4 cells <100/μL, and HIVRNA >1,000 copies/mL were eligible. We screened 362 subjects; 279 met inclusion criteria, 3 refused participation, and 276 were randomized. Participants received maraviroc 600 mg twice daily or placebo added to an ART regimen that included tenofovir, emtricitabine, and efavirenz for 48 weeks. Findings There were 276 patients randomized (140 received maraviroc and 136 placebo). There was no difference in the time to IRIS events between treatment arms (HR 1·08, 95% CI (0·66, 1·77), log-rank test p=0·743). In total, 64 (23%) patients had IRIS events, 33 (24%) in the maraviroc arm and 31 (23%) in the placebo arm (p=0·88). Interpretation Maraviroc had no significant effect on frequency, time or severity of IRIS events after ART initiation. Including a CCR5 inhibitor in an initial treatment regimen does not confer a meaningful protection from the occurrence of IRIS in persons with advanced HIV infection. Funding The trial was funded as investigator initiated research by Pfizer Inc, New York, NY, USA. Trial Registration ClinicalTrials.gov. ID: NCT00988780 (http://clinicaltrials.gov/ct2/show/NCT00988780) PMID:26366430

  12. Methotrexate therapy associates with reduced prevalence of the metabolic syndrome in rheumatoid arthritis patients over the age of 60- more than just an anti-inflammatory effect? A cross sectional study

    PubMed Central

    Toms, Tracey E; Panoulas, Vasileios F; John, Holly; Douglas, Karen MJ; Kitas, George D

    2009-01-01

    Introduction The metabolic syndrome (MetS) may contribute to the excess cardiovascular burden observed in rheumatoid arthritis (RA). The prevalence and associations of the MetS in RA remain uncertain: systemic inflammation and anti-rheumatic therapy may contribute. Methotrexate (MTX) use has recently been linked to a reduced presence of MetS, via an assumed generic anti-inflammatory mechanism. We aimed to: assess the prevalence of the MetS in RA; identify factors that associate with its presence; and assess their interaction with the potential influence of MTX. Methods MetS prevalence was assessed cross-sectionally in 400 RA patients, using five MetS definitions (National Cholesterol Education Programme 2004 and 2001, International Diabetes Federation, World Health Organisation and European Group for Study of Insulin Resistance). Logistic regression was used to identify independent predictors of the MetS. Further analysis established the nature of the association between MTX and the MetS. Results MetS prevalence rates varied from 12.1% to 45.3% in RA according to the definition used. Older age and higher HAQ scores associated with the presence of the MetS. MTX use, but not other disease modifying anti-rheumatic drugs (DMARDs) or glucocorticoids, associated with significantly reduced chance of having the MetS in RA (OR = 0.517, CI 0.33–0.81, P = 0.004). Conclusions The prevalence of the MetS in RA varies according to the definition used. MTX therapy, unlike other DMARDs or glucocorticoids, independently associates with a reduced propensity to MetS, suggesting a drug-specific mechanism, and makes MTX a good first-line DMARD in RA patients at high risk of developing the MetS, particularly those aged over 60 years. PMID:19607680

  13. [Sweet syndrome revealing leukemia].

    PubMed

    Elleuch, E; Hammami, B; Smaoui, F; Maaloul, I; Turki, H; Elloumi, M; Ben Jemaa, M

    2011-09-01

    Sweet syndrome is a neutrophilic dermatosis that can lead to various inflammatory and neoplastic pathologies. We report a case of Sweet syndrome revealing acute leukemia at a 13-year-old girl, who had no history of illness. The diagnosis was made in spite of atypical skin lesions and was confirmed by the skin biopsy and the bone marrow examination. In spite of corticosteroid therapy and chemotherapy, the patient died. Sweet syndrome's diagnosis requires an exhaustive etiologic survey. If there is no evidence of underlying disease, patients must be regularly monitored.

  14. Inflammatory response and the endothelium.

    PubMed

    Meroni, P L; Borghi, M O; Raschi, E; Ventura, D; Sarzi Puttini, P C; Atzeni, F; Lonati, L; Parati, G; Tincani, A; Mari, D; Tedesco, F

    2004-01-01

    Antiphospholipid-mediated endothelium perturbation plays a role in antiphospholipid syndrome (APS)-associated vasculopathy. Antiphospholipid antibodies activate endothelium both in vitro and in vivo experimental models by inducing a pro-inflammatory/-coagulant phenotype; the antibodies recognize beta2 glycoprotein I (beta2GPI) on human endothelial cells (EC) from different parts of the vasculature. In spite of such large in vitro evidence, few studies have addressed the issue whether or not a comparable endothelial perturbation might be detectable in vivo. We investigated several indirect ex vivo parameters of endothelial dysfunction: plasma levels of soluble adhesion molecules (sADM), soluble thrombomodulin (sTM), von Willebrand factor (vWF) and tissue plasminogen activator (t-PA) by solid-phase assays. The study included: patients with primary antiphospholipid syndrome (n=32), with the syndrome secondary to non-active systemic lupus erythematosus (SLE, n=10), six patients with persistent antiphospholipid positivity at medium/high titre without any clinical manifestation of the syndrome. Fifty-two age and sex matched healthy subjects have been enrolled as controls. In addition, circulating endothelial cells identified by flow cytometry and the brachial artery flow-mediated vasodilation (FMV) were evaluated in 26 patients (20 primary and 6 lupus syndromes) and 30 healthy controls. Plasma levels of soluble adhesion molecules did not differ from controls, while a significant increase in von Willebrand factor titres (P<0.05) was found. No significant difference was found regarding the number of circulating endothelial cells and flow-mediated vasodilation. As a whole, these findings do suggest that antiphospholipid antibodies per se are not able to support a full-blown endothelial perturbation in vivo. As shown in antiphospholipid syndrome experimental animal models, a two-hit hypothesis is suggested.

  15. Complex regional pain syndrome.

    PubMed

    Bruehl, Stephen

    2015-07-29

    Complex regional pain syndrome is a chronic pain condition characterized by autonomic and inflammatory features. It occurs acutely in about 7% of patients who have limb fractures, limb surgery, or other injuries. Many cases resolve within the first year, with a smaller subset progressing to the chronic form. This transition is often paralleled by a change from "warm complex regional pain syndrome," with inflammatory characteristics dominant, to "cold complex regional pain syndrome" in which autonomic features dominate. Multiple peripheral and central mechanisms seem to be involved, the relative contributions of which may differ between individuals and over time. Possible contributors include peripheral and central sensitization, autonomic changes and sympatho-afferent coupling, inflammatory and immune alterations, brain changes, and genetic and psychological factors. The syndrome is diagnosed purely on the basis of clinical signs and symptoms. Effective management of the chronic form of the syndrome is often challenging. Few high quality randomized controlled trials are available to support the efficacy of the most commonly used interventions. Reviews of available randomized trials suggest that physical and occupational therapy (including graded motor imagery and mirror therapy), bisphosphonates, calcitonin, subanesthetic intravenous ketamine, free radical scavengers, oral corticosteroids, and spinal cord stimulation may be effective treatments. Multidisciplinary clinical care, which centers around functionally focused therapies is recommended. Other interventions are used to facilitate engagement in functional therapies and to improve quality of life.

  16. Interleukin-17 in various ocular surface inflammatory diseases.

    PubMed

    Kang, Min Ho; Kim, Mee Kum; Lee, Hyun Joo; Lee, Hyeon Il; Wee, Won Ryang; Lee, Jin Hak

    2011-07-01

    Recently, the association of Th-17 cells or IL-17 with ocular inflammatory diseases such as uveitis, scleritis and dry eye syndrome was discovered. We assessed whether interleukin (IL)-17 was present in the tears of various ocular surface inflammatory diseases and the tear IL-17 concentrations were clinically correlated with various ocular surface inflammatory diseases. We measured concentrations of IL-17 in tears of normal subjects (n = 28) and patients (n = 141) with meibomian gland dysfunction (MGD), dry eye syndrome (DES), Sjögren syndrome (SS), Stevens-Johnson syndrome (SJS), graft-versus-host disease (GVHD), filamentary keratitis, and autoimmune keratitis associated with rheumatoid arthritis or systemic lupus erythematosus. Clinical epitheliopathy scores were based on the surface area of corneal and conjunctival fluorescein staining. The mean concentrations of IL-17 in tears of patients with filamentary keratitis, GVHD, autoimmune keratitis, SS, DES, MGD, SJS were significantly higher in order than that in normal subjects. Tear IL-17 concentration was significantly correlated with clinical epitheilopathy scores in the patients with systemic inflammatory disease, while tear IL-17 was not correlated with clinical severity of the cornea and conjunctiva in the dry eye patients without any systemic inflammatory disease. Tear IL-17 is likely to correlate clinically with corneal disease severity only in the patients with systemic inflammatory disease.

  17. How I Manage Heel Spur Syndrome.

    ERIC Educational Resources Information Center

    Seder, Joseph I.

    1987-01-01

    This article discusses plantar fascitis and heel spurs, the two contributing causes of heel spur syndrome. Treatment methods, which include rest, anti-inflammatory medication, shoe padding, and, as a last resort, surgery are described. (Author/MT)

  18. Auriculotemporal Syndrome (Frey Syndrome).

    PubMed

    Motz, Kevin M; Kim, Young J

    2016-04-01

    Frey syndrome is a common sequela of parotidectomy, and although it is not frequently manifested clinically, it can cause significant morbidity for those affected. Frey syndrome results from synkinetic autonomic reinnervation by transected postganglionic parasympathetic nerve fiber within the parotid gland to the overlying sweat glands of the skin. Many surgical techniques have been proposed to prevent the development of Frey syndrome. For those who develop clinical symptoms of Frey syndrome, objective testing can be performed with a Minor starch-iodine test. Some of the current methods to prevent and treat symptomatic Frey syndrome are reviewed. PMID:26902982

  19. Chronic inflammatory demyelinating polyneuropathy

    MedlinePlus

    Polyneuropathy - chronic inflammatory; CIDP; Chronic inflammatory polyneuropathy; Guillain-Barré - CIDP ... CIDP is one cause of damage to nerves outside the brain or spinal cord ( peripheral neuropathy ). Polyneuropathy ...

  20. Tourette syndrome

    MedlinePlus

    Gilles de la Tourette syndrome; Tic disorders - Tourette syndrome ... Tourette syndrome is named for Georges Gilles de la Tourette, who first described this disorder in 1885. The disorder is likely passed down through families. The syndrome may be linked to ...

  1. Syndrome in question: antisynthetase syndrome (anti-PL-7)*

    PubMed Central

    Esposito, Ana Cláudia Cavalcante; Gige, Tatiana Cristina; Miot, Hélio Amante

    2016-01-01

    Antisynthetase syndrome is a rare autoimmune disease characterized by interstitial lung disease and/or inflammatory myositis, with positive antisynthetase antibodies (anti-Jo-1, anti-PL-7, anti-PL-12, ZO, OJ, anti-KE or KS). Other symptoms described include: non-erosive arthritis, fever, Raynaud's phenomenon, and "mechanic's hands." The first therapeutic option is corticotherapy, followed by other immunosuppressants. The prognosis of the disease is quite limited when compared to other inflammatory myopathies with negative antisynthetase antibodies.

  2. Anti-Inflammatory Iridoids of Botanical Origin

    PubMed Central

    Viljoen, A; Mncwangi, N; Vermaak, I

    2012-01-01

    Inflammation is a manifestation of a wide range of disorders which include; arthritis, atherosclerosis, Alzheimer’s disease, inflammatory bowel syndrome, physical injury and infection amongst many others. Common treatment modalities are usually non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, paracetamol, indomethacin and ibuprofen as well as corticosteroids such as prednisone. These however, may be associated with a host of side effects due to non-selectivity for cyclooxygenase (COX) enzymes involved in inflammation and those with selectivity may be highly priced. Thus, there is a continuing search for safe and effective anti-inflammatory molecules from natural sources. Research has confirmed that iridoids exhibit promising anti-inflammatory activity which may be beneficial in the treatment of inflammation. Iridoids are secondary metabolites present in various plants, especially in species belonging to the Apocynaceae, Lamiaceae, Loganiaceae, Rubiaceae, Scrophulariaceae and Verbenaceae families. Many of these ethnobotanicals have an illustrious history of traditional use alluding to their use to treat inflammation. Although iridoids exhibit a wide range of pharmacological activities such as cardiovascular, hepatoprotection, hypoglycaemic, antimutagenic, antispasmodic, anti-tumour, antiviral, immunomodulation and purgative effects this review will acutely focus on their anti-inflammatory properties. The paper aims to present a summary for the most prominent iridoid-containing plants for which anti-inflammatory activity has been demonstrated in vitro and / or in vivo. PMID:22414102

  3. Metabolic Syndrome, Androgens, and Hypertension

    PubMed Central

    Moulana, Mohadetheh; Lima, Roberta; Reckelhoff, Jane F.

    2013-01-01

    Obesity is one of the constellation of factors that make up the definition of the metabolic syndrome. Metabolic syndrome is also associated with insulin resistance, dyslipidemia, hypertriglyceridemia, and type 2 diabetes mellitus. The presence of obesity and metabolic syndrome in men and women is also associated with increased risk of cardiovascular disease and hypertension. In men, obesity and metabolic syndrome are associated with reductions in testosterone levels. In women, obesity and metabolic syndrome is associated with increases in androgen levels. In men reductions in androgen levels is associated with inflammation. Androgen supplements reduce inflammation in men. In women, increases in androgens are associated with increases in inflammatory cytokines, and reducing androgens reduces inflammation. In this review the possibility that androgens may have different effects on metabolic syndrome and its sequelae in males and females will be discussed. PMID:21274756

  4. Iliotibial band friction syndrome.

    PubMed

    Kirk, K L; Kuklo, T; Klemme, W

    2000-11-01

    Overuse knee injuries are common, but ITBFS is often overlooked as a cause of lateral knee pain in an active population. Iliotibial band friction syndrome is an overuse injury usually seen in long distance runners, cyclists, and military personnel. The exact incidence of the syndrome has been estimated to range from 1.6%-52% depending on the population studied. The diagnosis is often made from a thorough history and clinical examination with an infrequent need for additional studies. Treatment is mostly conservative consisting of rest and anti-inflammatory agents, with only the refractory cases requiring surgical resection of the impinging portion of the ITB.

  5. Inflammatory myofibroblastic tumor

    PubMed Central

    Palaskar, Sangeeta; Koshti, Supriya; Maralingannavar, Mahesh; Bartake, Anirudha

    2011-01-01

    Inflammatory myofibroblastic tumor is an uncommon lesion of unknown cause. It encompasses a spectrum of myofibroblastic proliferation along with varying amount of inflammatory infiltrate. A number of terms have been applied to the lesion, namely, inflammatory pseudotumor, fibrous xanthoma, plasma cell granuloma, pseudosarcoma, lymphoid hamartoma, myxoid hamartoma, inflammatory myofibrohistiocytic proliferation, benign myofibroblatoma, and most recently, inflammatory myofibroblastic tumor. The diverse nomenclature is mostly descriptive and reflects the uncertainty regarding true biologic nature of these lesions. Recently, the concept of this lesion being reactive has been challenged based on the clinical demonstration of recurrences and metastasis and cytogenetic evidence of acquired clonal chromosomal abnormalities. We hereby report a case of inflammatory pseudotumor and review its inflammatory versus neoplastic behavior. PMID:22346151

  6. Observational Study of the Genetic Architecture of Neutrophil-Mediated Inflammatory Skin Diseases

    ClinicalTrials.gov

    2016-09-26

    Other Specified Inflammatory Disorders of Skin or Subcutaneous Tissue; Pyoderma Gangrenosum; Erosive Pustular Dermatosis of the Scalp; Sweet's Syndrome; Behcet's Disease; Bowel-associated Dermatosis-arthritis Syndrome; Pustular Psoriasis; Acute Generalized Exanthematous Pustulosis; Keratoderma Blenorrhagicum; Sneddon-Wilkinson Disease; IgA Pemphigus; Amicrobial Pustulosis of the Folds; Infantile Acropustulosis; Transient Neonatal Pustulosis; Neutrophilic Eccrine Hidradenitis; Rheumatoid Neutrophilic Dermatitis; Neutrophilic Urticaria; Still's Disease; Erythema Marginatum; Unclassified Periodic Fever Syndromes / Autoinflammatory Syndromes; Dermatitis Herpetiformis; Linear IgA Bullous Dermatosis; Bullous Systemic Lupus Erythematosus; Inflammatory Epidermolysis Bullosa Aquisita; Neutrophilic Dermatosis of the Dorsal Hands (Pustular Vasculitis); Small Vessel Vasculitis Including Urticarial Vasculitis; Erythema Elevatum Diutinum; Medium Vessel Vasculitis

  7. Inflammatory myopathies and lymphoma.

    PubMed

    Stübgen, Joerg-Patrick

    2016-10-15

    The inflammatory myopathies comprise a group of immune-mediated muscle diseases. Lymphoma is a term for a variety of lymphatic system malignancies. Autoimmune diseases and lymphoproliferative malignancies share a complex bidirectional relationship. A causal relationship between inflammatory mypathies and lymphoma has not been established. The diagnosis/treatment of inflammatory myopathy usually precedes the detection/diagnosis of lymphoma. Immune system dysregulation presumably underlies the evolution of lymphoma in patients with inflammatory myopathies. Inflammatory activity with chronic B-cell activation and/or antigen stimulation is deemed the major risk factor for lymphoma in patients with autoimmunity. A "paraneoplastic" phenomenon or the effects of immunosuppressive therapy may be alternative immune-based mechanisms. In chronic lymphocytic leukemia immune system disturbance rarely results in non-hematological autoimmune disease, including inflammatory myopathies. PMID:27653927

  8. A scarlet pimpernel for the resolution of inflammation? The role of supra-therapeutic doses of cobalamin, in the treatment of systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, and septic or traumatic shock.

    PubMed

    Wheatley, Carmen

    2006-01-01

    Cobalamin carrier proteins,the Transcobalamins (TCS), are elevated during trauma, infections and chronic inflammatory conditions. This remains un-explained. It is proposed that such TC elevations signal a need for cobalamin central to the resolution of inflammation. Thus Cobalamin may regulate the transcription factor, NFkappaB, activation or suppression of which determines the inflammatory response and its resolution. Such regulation may involve at least 5 separate mechanisms: (i) hormone-like regulation of TNFalpha, through reduction of excess NO by cobalamin, as well as through the selective inhibition, in tandem with glutathione, of inducible nitric oxide synthase; (ii) quenching of nitric oxide radicals and reactive oxygen species, enhanced by cobalamin's glutathione sparing effect; (iii) the promotion of acetylcholine synthesis, central to the neuro-immune cholinergic anti-inflammatory pathway; (iv) the promotion of oxidative phosphorylation; (v) and a bacteriostatic role of the TCS released by neutrophil secondary granules during phagocytosis, which also appears to modulate the inflammatory response. TC elevations are dependent on NFkappaB activation, through crosstalk between NFkappaB and Sp1, another member of the helix-loop-helix protein family, which directly mediates transcription of the TCII gene. Sp1 also has binding sites on the TNFalpha and EGF gene promoters. NFkappaB may thus ensure sufficient cobalamin to determine its own eventual suppression. Cobalamin's established regulation of EGF may additionally preserve normal function of macrophages and the coagulation cascade in wound healing. By regulating NFkappaB, Cobalamin may also be the as yet unidentified mediator needed to potentiate the anti-inflammatory action of eicosanoids derived from omega-3 essential fatty acids. Moreover, animal and human clinical data suggests that high dose cobalamin may prove a promising approach to SIRS/sepsis/septic and traumatic shock. PMID:16545917

  9. Anti-inflammatory iridoids of botanical origin.

    PubMed

    Viljoen, A; Mncwangi, N; Vermaak, I

    2012-01-01

    Inflammation is a manifestation of a wide range of disorders which include; arthritis, atherosclerosis, Alzheimer's disease, inflammatory bowel syndrome, physical injury and infection amongst many others. Common treatment modalities are usually nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, paracetamol, indomethacin and ibuprofen as well as corticosteroids such as prednisone. These however, may be associated with a host of side effects due to non-selectivity for cyclooxygenase (COX) enzymes involved in inflammation and those with selectivity may be highly priced. Thus, there is a continuing search for safe and effective antiinflammatory molecules from natural sources. Research has confirmed that iridoids exhibit promising anti-inflammatory activity which may be beneficial in the treatment of inflammation. Iridoids are secondary metabolites present in various plants, especially in species belonging to the Apocynaceae, Lamiaceae, Loganiaceae, Rubiaceae, Scrophulariaceae and Verbenaceae families. Many of these ethnobotanicals have an illustrious history of traditional use alluding to their use to treat inflammation. Although iridoids exhibit a wide range of pharmacological activities such as cardiovascular, hepatoprotection, hypoglycaemic, antimutagenic, antispasmodic, anti-tumour, antiviral, immunomodulation and purgative effects this review will acutely focus on their anti-inflammatory properties. The paper aims to present a summary for the most prominent iridoid-containing plants for which anti-inflammatory activity has been demonstrated in vitro and / or in vivo.

  10. Anti-inflammatory iridoids of botanical origin.

    PubMed

    Viljoen, A; Mncwangi, N; Vermaak, I

    2012-01-01

    Inflammation is a manifestation of a wide range of disorders which include; arthritis, atherosclerosis, Alzheimer's disease, inflammatory bowel syndrome, physical injury and infection amongst many others. Common treatment modalities are usually nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, paracetamol, indomethacin and ibuprofen as well as corticosteroids such as prednisone. These however, may be associated with a host of side effects due to non-selectivity for cyclooxygenase (COX) enzymes involved in inflammation and those with selectivity may be highly priced. Thus, there is a continuing search for safe and effective antiinflammatory molecules from natural sources. Research has confirmed that iridoids exhibit promising anti-inflammatory activity which may be beneficial in the treatment of inflammation. Iridoids are secondary metabolites present in various plants, especially in species belonging to the Apocynaceae, Lamiaceae, Loganiaceae, Rubiaceae, Scrophulariaceae and Verbenaceae families. Many of these ethnobotanicals have an illustrious history of traditional use alluding to their use to treat inflammation. Although iridoids exhibit a wide range of pharmacological activities such as cardiovascular, hepatoprotection, hypoglycaemic, antimutagenic, antispasmodic, anti-tumour, antiviral, immunomodulation and purgative effects this review will acutely focus on their anti-inflammatory properties. The paper aims to present a summary for the most prominent iridoid-containing plants for which anti-inflammatory activity has been demonstrated in vitro and / or in vivo. PMID:22414102

  11. Brown Syndrome

    MedlinePlus

    ... Does Brown syndrome cause eye problems besides abnormal eye movements? Some children with Brown syndrome have poor binocular ... In the congenital form of Brown syndrome, the eye movement problem is usually constant and unlikely to resolve ...

  12. Dravet Syndrome

    MedlinePlus

    ... NINDS Dravet Syndrome Information Page Synonym(s): Severe Myoclonic Epilepsy of Infancy (SMEI) Table of Contents (click to ... Dravet Syndrome? Dravet syndrome, also called severe myoclonic epilepsy of infancy (SMEI), is a severe form of ...

  13. Fahr's Syndrome

    MedlinePlus

    ... Awards Enhancing Diversity Find People About NINDS NINDS Fahr's Syndrome Information Page Synonym(s): Familial Idiopathic Basal Ganglia ... is being done? Clinical Trials Organizations What is Fahr's Syndrome? Fahr's Syndrome is a rare, genetically dominant, ...

  14. Cushing syndrome

    MedlinePlus

    Hypercortisolism; Cortisol excess ... The most common cause of Cushing syndrome is taking too much glucocorticosteroid medicine. This form of Cushing syndrome is called exogenous Cushing syndrome . Prednisone, dexamethasone, and prednisolone are ...

  15. Williams syndrome

    MedlinePlus

    Williams-Beuren syndrome ... Williams syndrome is caused by not having a copy of several genes. Parents may not have any family history of the condition. However, people with Williams syndrome have a 50% chance of passing the ...

  16. Curcumin in inflammatory diseases.

    PubMed

    Shehzad, Adeeb; Rehman, Gauhar; Lee, Young Sup

    2013-01-01

    Curcumin (diferuloylmethane), a yellow coloring agent extracted from turmeric is also used as a remedy for the treatment and prevention of inflammatory diseases. Acute and chronic inflammation is a major factor in the progression of obesity, type II diabetes, arthritis, pancreatitis, cardiovascular, neurodegenerative and metabolic diseases, as well as certain types of cancer. Turmeric has a long history of use in Ayurvedic medicine for the treatment of inflammatory disorders. Recent studies on the efficacy and therapeutic applicability of turmeric have suggested that the active ingredient of tumeric is curcumin. Further, compelling evidence has shown that curcumin has the ability to inhibit inflammatory cell proliferation, invasion, and angiogenesis through multiple molecular targets and mechanisms of action. Curcumin is safe, non-toxic, and mediates its anti-inflammatory effects through the down-regulation of inflammatory transcription factors, cytokines, redox status, protein kinases, and enzymes that all promote inflammation. In addition, curcumin induces apoptosis through mitochondrial and receptor-mediated pathways, as well as activation of caspase cascades. In the current study, the anti-inflammatory effects of curcumin were evaluated relative to various chronic inflammatory diseases. Based on the available pharmacological data obtained from in vitro and in vivo research, as well as clinical trials, an opportunity exists to translate curcumin into clinics for the prevention of inflammatory diseases in the near future. PMID:23281076

  17. Inflammatory Bowel Disease.

    PubMed

    2016-01-01

    Inflammation response plays an important role in host survival, and it also leads to acute and chronic inflammatory diseases such as rheumatoid arthritis, bowel diseases, allergic rhinitis, asthma, atopic dermatitis and various neurodegenerative diseases. During the course of inflammation, the ROS level increases. In addition to ROS, several inflammatory mediators produced at the site lead to numerous cell-mediated damages. Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is a chronic intestinal disorder resulting from a dysfunctional epithelial, innate and adaptive immune response to intestinal microorganisms. The methods involving indomethacin-induced enterocolitis in rats with macroscopic changes of IBD, myeloperoxidase assay, microscopic (histologic) characters and biochemical parameters are discussed.

  18. Cogan's syndrome: an oculo-audiovestibular disease

    PubMed Central

    Berrocal, J; Vargas, J; Vaquero, M; y, C; Ramirez-Camacho, R

    1999-01-01

    Typical Cogan's syndrome is a rare disease of young adults consisting of flares of interstitial keratitis and sudden onset of Ménière-like attacks (nausea, vomiting, tinnitus, vertigo and hearing loss). Life-threatening aortic insufficiency develops in 10% of reported cases. Atypical Cogan's syndrome (audiovestibular dysfunction with other types of inflammatory eye disease) is associated with vasculitis in 20% of cases and has a less favourable prognosis than typical Cogan's syndrome.


Keywords: Cogan's syndrome; hearing loss; autoimmune disease PMID:10533627

  19. [Diagnostic tools in inflammatory bowel diseases].

    PubMed

    Bouhnik, Yoram

    2005-05-15

    The two major inflammatory bowel diseases, Crohn's disease (CD) and ulcerative colitis (UC), represent clinicopathologic entities that traditionally have been diagnosed on the basis of a combination of clinical, radiologic, endoscopic, and histologic features. The presence of an inflammatory syndrome associated with typical clinical manifestations must lead to perform endoscopic examinations. Ileocolonoscopy plays an integral role in establishing the diagnosis, excluding other etiologies, distinguishing Crohn's disease from ulcerative colitis, defining the patterns, extent, and activity of mucosal inflammation, and obtaining mucosal tissue for histologic evaluation of inflammatory bowel disease. Small bowel follow through is still a major examination. However, the role of CT and MRI (using enteroclysis) in the imaging of inflammatory bowel disease has also increased in importance. Capsule endoscopy could be a valuable diagnostic tool in patients with suspected Crohn's disease that has not been confirmed using standard imaging techniques. Serum perinuclear antineutrophil cytoplasmic antibodies (pANCA) and anti-Saccharomyces cerevisiae antibodies (ASCA) have recently been added to our diagnostic armamentarium. Serology may prove to be useful in predicting the evolution of indeterminate colitis. Substantial progress could come from the improving of serologic and genetic tests in the future. PMID:16052968

  20. Pelvic Inflammatory Disease

    MedlinePlus

    Pelvic inflammatory disease (PID) is an infection and inflammation of the uterus, ovaries, and other female reproductive organs. It causes scarring ... United States. Gonorrhea and chlamydia, two sexually transmitted diseases, are the most common causes of PID. Other ...

  1. Anti-inflammatory Diets.

    PubMed

    Sears, Barry

    2015-01-01

    Chronic disease is driven by inflammation. This article will provide an overview on how the balance of macronutrients and omega-6 and omega-3 fatty acids in the diet can alter the expression of inflammatory genes. In particular, how the balance of the protein to glycemic load of a meal can alter the generation of insulin and glucagon and the how the balance of omega-6 and omega-3 fatty acids can effect eicosanoid formation. Clinical results on the reduction of inflammation following anti-inflammatory diets are discussed as well as the molecular targets of anti-inflammatory nutrition. To overcome silent inflammation requires an anti-inflammatory diet (with omega-3s and polyphenols, in particular those of Maqui). The most important aspect of such an anti-inflammatory diet is the stabilization of insulin and reduced intake of omega-6 fatty acids. The ultimate treatment lies in reestablishing hormonal and genetic balance to generate satiety instead of constant hunger. Anti-inflammatory nutrition, balanced 40:30:30 with caloric restriction, should be considered as a form of gene silencing technology, in particular the silencing of the genes involved in the generation of silent inflammation. To this anti-inflammatory diet foundation supplemental omega-3 fatty acids at the level of 2-3 g of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) per day should be added. Finally, a diet rich in colorful, nonstarchy vegetables would contribute adequate amounts of polyphenols to help not only to inhibit nuclear factor (NF)-κB (primary molecular target of inflammation) but also activate AMP kinase. Understanding the impact of an anti-inflammatory diet on silent inflammation can elevate the diet from simply a source of calories to being on the cutting edge of gene-silencing technology. PMID:26400429

  2. Psoriasis and Metabolic Syndrome – scientific evidence and therapeutic implications

    PubMed Central

    Voiculescu, VM; Lupu, M; Papagheorghe, L; Giurcaneanu, C; Micu, E

    2014-01-01

    Psoriasis is a chronic inflammatory disease, predominantly affecting the skin, being included in the group of Immune Mediated Inflammatory Diseases. Growing evidence from the last 10 years suggests that several systemic conditions like metabolic syndrome, cardiovascular disease, diabetes, psychological disorders or inflammatory bowel disease are prevalent in psoriasis patients. The linker might be the chronic secretion of pro-inflammatory cytokines. In this current review, the scientific evidence that explains the relationship between psoriasis and the metabolic syndrome in particular will be addressed, as the metabolic syndrome comprises a group of risk factors for cardiovascular disease, thus offering an overall picture of the systemic involvement in psoriasis. An integrated approach, with an early detection and treatment of the components of the metabolic syndrome, are important steps in psoriasis management. Attention should be paid on influence of psoriasis treatment upon comorbidities and vice-versa. PMID:25713604

  3. Psoriasis and Metabolic Syndrome--scientific evidence and therapeutic implications.

    PubMed

    Voiculescu, V M; Lupu, M; Papagheorghe, L; Giurcaneanu, C; Micu, E

    2014-01-01

    Psoriasis is a chronic inflammatory disease, predominantly affecting the skin, being included in the group of Immune Mediated Inflammatory Diseases. Growing evidence from the last 10 years suggests that several systemic conditions like metabolic syndrome, cardiovascular disease, diabetes, psychological disorders or inflammatory bowel disease are prevalent in psoriasis patients. The linker might be the chronic secretion of pro-inflammatory cytokines. In this current review, the scientific evidence that explains the relationship between psoriasis and the metabolic syndrome in particular will be addressed, as the metabolic syndrome comprises a group of risk factors for cardiovascular disease, thus offering an overall picture of the systemic involvement in psoriasis. An integrated approach, with an early detection and treatment of the components of the metabolic syndrome, are important steps in psoriasis management. Attention should be paid on influence of psoriasis treatment upon comorbidities and vice-versa.

  4. Pelvic Inflammatory Disease (PID)

    MedlinePlus

    ... herpes, syphilis, and infection with human immunodeficiency virus (HIV, the cause of acquired immunodeficiency syndrome [AIDS]). Ultrasonography: A test in which sound waves are used to examine internal structures. During pregnancy, it can be used to examine ...

  5. Histiocytoid Sweet's syndrome in a patient with myelodsyplastic syndrome: report and review of the literature.

    PubMed

    Shalaby, Michael M; Riahi, Ryan R; Rosen, Les B; Soine, Erik J

    2016-01-01

    The neutrophilic dermatoses are a group of disorders characterized by skin lesions for which histological examination reveals intense epidermal and/or dermal inflammatory infiltrates composed primarily of neutrophils without evidence of infection. The myelodysplastic syndromes consist of a heterogeneous group of malignant hematopoietic stem cell disorders characterized by dysplastic and inadequate blood cell production with a variable risk of transformation to acute leukemia. Rarely, histiocytoid Sweet's syndrome occurring in patients with myelodysplastic syndrome has been described. We present a case of a 66-year-old woman with a history of myelodysplastic syndrome who developed histiocytoid Sweet's syndrome. We also review the literature and characterize patients with myelodysplastic syndrome who have developed histiocytoid Sweet's syndrome.

  6. Dorfman-Chanarin syndrome.

    PubMed

    Gandhi, Vijay; Aggarwal, Puneet; Dhawan, Jyoti; Singh, Usha Rani; Bhattacharya, S N

    2007-01-01

    A four-year-old girl was brought to the dermatology outpatient department with scaling all over the body since birth. She had history of episodic vomiting and abdominal distension. A dermatological diagnosis of lamellar ichthyosis was made. Abdominal examination revealed a nontender hepatomegaly, fatty liver on ultrasonography and deranged liver function tests. Peripheral blood smear showed lipid vacuoles in the granulocytes consistent with Jordans' anomaly. Similar lipid vacuoles were seen in the basal layer in skin biopsy. An inflammatory infiltrate, moderate fibrosis in the portal tract and diffuse severe fatty change in hepatocytes were seen in liver biopsy. The patient was diagnosed as a case of Dorfman-Chanarin syndrome.

  7. Inflammation: a trigger for acute coronary syndrome.

    PubMed

    Sager, Hendrik B; Nahrendorf, Matthias

    2016-09-01

    Atherosclerosis is a chronic inflammatory disease of the vessel wall and a major cause of death worldwide. One of atherosclerosis' most dreadful complications are acute coronary syndromes that comprise ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction, and unstable angina. We now understand that inflammation substantially contributes to the initiation, progression, and destabilization of atherosclerosis. In this review, we will focus on the role of inflammatory leukocytes, which are the cellular protagonists of vascular inflammation, in triggering disease progression and, ultimately, the destabilization that causes acute coronary syndromes. PMID:27273431

  8. Glucocorticoid pharmacogenetics in pediatric idiopathic nephrotic syndrome.

    PubMed

    Cuzzoni, Eva; De Iudicibus, Sara; Franca, Raffaella; Stocco, Gabriele; Lucafò, Marianna; Pelin, Marco; Favretto, Diego; Pasini, Andrea; Montini, Giovanni; Decorti, Giuliana

    2015-01-01

    Idiopathic nephrotic syndrome represents the most common type of primary glomerular disease in children: glucocorticoids (GCs) are the first-line therapy, even if considerable interindividual differences in their efficacy and side effects have been reported. Immunosuppressive and anti-inflammatory effects of these drugs are mainly due to the GC-mediated transcription regulation of pro- and anti-inflammatory genes. This mechanism of action is the result of a complex multistep pathway that involves the glucocorticoid receptor and several other proteins, encoded by polymorphic genes. Aim of this review is to highlight the current knowledge on genetic variants that could affect GC response, particularly focusing on children with idiopathic nephrotic syndrome.

  9. [Acute-Onset Chronic Inflammatory Demyelinating Polyradiculoneuropathy].

    PubMed

    Kanbayashi, Takamichi; Sonoo, Masahiro

    2015-11-01

    Chronic inflammatory demyelinating polyneuropathy (CIDP) is characterized by an insidious onset showing progression over two months. However, up to 16% of CIDP patients may show acute presentation similar to Guillain-Barré syndrome (GBS). Such cases are termed acute-onset CIDP (A-CIDP). Distinguishing A-CIDP from GBS, especially the acute inflammatory demyelinating polyneuropathy (AIDP) subtype, is critical because therapeutic strategies and outcomes may differ between the two syndromes. Regarding clinical features, A-CIDP is less likely to have autonomic nervous system involvement, facial weakness, a preceding infectious illness, or the need for mechanical ventilation, in comparison with AIDP. Electrophysiological features are usually quite similar between the two, although follow-up studies may elucidate key differences. Around 8%-16% of GBS patients may show clinical deterioration shortly after improvement or stabilization following initial immunological therapy. Such a situation is termed treatment-related fluctuation (TRF; GBS-TRF). The distinction between GBS-TRF and A-CIDP is an important clinical issue because maintenance treatment is often required in CIDP. The diagnosis of A-CIDP should be considered when the condition of a patient with GBS deteriorates after nine weeks from onset, or when deterioration occurs three times or more.

  10. Inflammatory bowel disease

    PubMed Central

    Beattie, R M; Croft, N M; Fell, J M; Afzal, N A; Heuschkel, R B

    2006-01-01

    Twenty five per cent of inflammatory bowel disease presents in childhood. Growth and nutrition are key issues in the management with the aim of treatment being to induce and then maintain disease remission with minimal side effects. Only 25% of Crohn's disease presents with the classic triad of abdominal pain, weight loss, and diarrhoea. Most children with ulcerative colitis have blood in the stool at presentation. Inflammatory markers are usually although not invariably raised at presentation (particularly in Crohn's disease). Full investigation includes upper gastrointestinal endoscopy and ileocolonoscopy. Treatment requires multidisciplinary input as part of a clinical network led by a paediatrician with special expertise in the management of the condition. PMID:16632672

  11. Inflammatory and toxic myopathy.

    PubMed

    Teener, James W

    2012-11-01

    Although muscle diseases are relatively rare, several treatable myopathies must be recognized by the clinician to maximize the possibility of restoring strength in affected patients. The inflammatory myopathies, including polymyositis, dermatomyositis, inflammatory necrotizing myopathy, and myositis in association with mixed connective tissue disease, typically respond well to immunosuppressive treatment. Inclusion body myositis, a myopathy that has features of both inflammation and primary degeneration, may not be treatable at this time, but treatments are actively being sought. Muscle dysfunction caused by toxins must also be recognized because removal of the offending toxin usually results in restoration of normal muscle function. Important muscle toxins include cholesterol-lowering medications, colchicine, zidovudine, corticosteroids, emetine, and ethanol.

  12. Turner Syndrome

    MedlinePlus

    Turner syndrome is a genetic disorder that affects a girl's development. The cause is a missing or ... t work properly. Other physical features typical of Turner syndrome are Short, "webbed" neck with folds of ...

  13. LEOPARD syndrome

    MedlinePlus

    LEOPARD syndrome is a very rare inherited disorder in which there are problems with the skin, face, ... LEOPARD syndrome is inherited as an autosomal dominant trait. This means the person only needs the abnormal ...

  14. Pendred Syndrome

    MedlinePlus

    ... thyroid gland. Pendred syndrome also can affect the vestibular system, which controls balance. Some people with Pendred syndrome will show vestibular weakness when their balance is tested. However, the ...

  15. Bloom's Syndrome

    MedlinePlus

    ... Glycogen Storage Disease, Type 1A Joubert Syndrome Maple Syrup Urine Disease and DLD Mucolipidosis IV (MLIV) Nemaline ... Glycogen Storage Disease, Type 1A Joubert Syndrome Maple Syrup Urine Disease and DLD Mucolipidosis IV (MLIV) Nemaline ...

  16. Metabolic Syndrome

    MedlinePlus

    Metabolic syndrome is a group of conditions that put you at risk for heart disease and diabetes. These ... doctors agree on the definition or cause of metabolic syndrome. The cause might be insulin resistance. Insulin is ...

  17. Cushing's Syndrome

    MedlinePlus

    ... Cushing's syndrome, also called hypercortisolism , is a rare endocrine disorder caused by chronic exposure of the body's tissues ... removing the tumor while minimizing the chance of endocrine deficiency or long-term ... for Cushing's Syndrome Clinical Trials ...

  18. Rett Syndrome

    MedlinePlus

    Rett syndrome is a rare genetic disease that causes developmental and nervous system problems, mostly in girls. It's related to autism spectrum disorder. Babies with Rett syndrome seem to grow and develop normally at first. ...

  19. Piriformis syndrome

    MedlinePlus

    Pseudosciatica; Wallet sciatica; Hip socket neuropathy; Pelvic outlet syndrome; Low back pain - piriformis ... Sciatica is the main symptom of piriformis syndrome. Other symptoms include: Tenderness or a dull ache in ...

  20. Angelman Syndrome

    MedlinePlus

    ... causes developmental delay and neurological problems. The physician Harry Angelman first delineated the syndrome in 1965, when ... 202-534-3731 Prader-Willi Syndrome Association 8588 Potter Park Drive Suite 500 Sarasota, FL 34238 national@ ...

  1. [Syndrome of multiple organ failure].

    PubMed

    Charbonneau, P; Suisse, A

    1990-11-01

    The multiple organ failure syndrome (MOF) is a relatively new entity defined as the successive occurrence of respiratory (ARDS), hepatic, renal, myocardial, gastro-intestinal or neurological failure in patients with hyperkinetic haemodynamic and hypermetabolic states. The etiologies are: infection, septic and non-septic shock, burns and multiple injuries. The MOF syndrome is considered to be a generalised "inflammatory reaction" to tissue aggression involving a cascade of mediatory factors (TNF, interleukines...) of macrophagic, lymphocytic origin, causing multiple organ failure. The treatment depends on early correction of cellular hypoxia related to circulatory disturbances, nutritional support, anti-infective therapy and, in the near future, "control of mediator activity" (immunotherapy).

  2. Fatigue syndrome in sarcoidosis.

    PubMed

    Górski, Witold; Piotrowski, Wojciech J

    2016-01-01

    Sarcoidosis is an inflammatory disease of unknown etiology. Most commonly it results in the formation of non-caseating granulomas in intrathoracic lymph nodes and lung parenchyma, but the clinical course and picture may be complicated by extrapulmonary involvement and many non-respiratory signs and symptoms which are directly related to the disease. In addition, sarcoidosis patients may suffer from a plethora of symptoms of uncertain or unknown origin. Fatigue is one of these symptoms, and according to some authors it is reported by the majority of patients with active sarcoidosis, but also by a smaller proportion of patients with inactive sarcoidosis, or even with complete clinical and radiological remission. Therefore the term fatigue syndrome is frequently used to name this clinical problem. The definition of fatigue syndrome in sarcoidosis is imprecise and the syndrome is usually recognized by use of validated questionnaires. In this review the uptodate knowledge in this field was presented and different challenges connected with this syndrome were described.

  3. Gut microbiome and metabolic syndrome.

    PubMed

    Mazidi, Mohsen; Rezaie, Peyman; Kengne, Andre Pascal; Mobarhan, Majid Ghayour; Ferns, Gordon A

    2016-01-01

    The gut microbiome contributes approximately 2kg of the whole body weight, and recent studies suggest that gut microbiota has a profound effect on human metabolism, potentially contributing to several features of the metabolic syndrome. Metabolic syndrome is defined by a clustering of metabolic disorders that include central adiposity with visceral fat accumulation, dyslipidemia, insulin resistance, dysglycemia and non-optimal blood pressure levels. Metabolic syndrome is associated with an increased risk of cardiovascular diseases and type 2 diabetes. It is estimated that around 20-25 percent of the world's adult population has metabolic syndrome. In this manuscript, we have reviewed the existing data linking gut microbiome with metabolic syndrome. Existing evidence from studies both in animals and humans support a link between gut microbiome and various components of metabolic syndrome. Possible pathways include involvement with energy homeostasis and metabolic processes, modulation of inflammatory signaling pathways, interferences with the immune system, and interference with the renin-angiotensin system. Modification of gut microbiota via prebiotics, probiotics or other dietary interventions has provided evidence to support a possible beneficial effect of interventions targeting gut microbiota modulation to treat components or complications of metabolic syndrome. PMID:26916014

  4. Gut microbiome and metabolic syndrome.

    PubMed

    Mazidi, Mohsen; Rezaie, Peyman; Kengne, Andre Pascal; Mobarhan, Majid Ghayour; Ferns, Gordon A

    2016-01-01

    The gut microbiome contributes approximately 2kg of the whole body weight, and recent studies suggest that gut microbiota has a profound effect on human metabolism, potentially contributing to several features of the metabolic syndrome. Metabolic syndrome is defined by a clustering of metabolic disorders that include central adiposity with visceral fat accumulation, dyslipidemia, insulin resistance, dysglycemia and non-optimal blood pressure levels. Metabolic syndrome is associated with an increased risk of cardiovascular diseases and type 2 diabetes. It is estimated that around 20-25 percent of the world's adult population has metabolic syndrome. In this manuscript, we have reviewed the existing data linking gut microbiome with metabolic syndrome. Existing evidence from studies both in animals and humans support a link between gut microbiome and various components of metabolic syndrome. Possible pathways include involvement with energy homeostasis and metabolic processes, modulation of inflammatory signaling pathways, interferences with the immune system, and interference with the renin-angiotensin system. Modification of gut microbiota via prebiotics, probiotics or other dietary interventions has provided evidence to support a possible beneficial effect of interventions targeting gut microbiota modulation to treat components or complications of metabolic syndrome.

  5. Sweet's syndrome with idiopathic thrombocythemia

    PubMed Central

    Kaszewski, Sebastian; Protas-Drozd, Franciszka; Placek, Waldemar; Jakubowski, Sebastian

    2014-01-01

    Diagnosis of paraneoplastic skin syndromes associating neoplastic processes is assumed as the crucial aspect of dermatological practice. Knowledge of clinical findings of dermatoses suggesting coincidence of malignant proliferative processes facilitates diagnostic and therapeutic procedures. We would like to present a case of Sweet's syndrome, qualified for comparative paraneoplastic skin syndromes. Sweet's syndrome, acute, febrile neutrophilic dermatosis, was first described by Robert Douglas Sweet in 1964 as a disorder characterized by fever, skin lesions of erythematous-infiltrative character, leukocytosis with neutrophilia and dense infiltrations of dermis by mature neutrophils. Sweet's syndrome aetiology is not fully understood, although cytokine abnormalities suggest that Th1 lymphocytes play an important role in pathogenesis of the dermatosis. Factors inducing Sweet's syndrome include: haematopoietic hyperplasia; neoplasms: genitourinary, breast, gastrointestinal; infections of the respiratory and alimentary system; inflammatory bowel diseases; drugs; pregnancy and vaccinations. Systemic corticosteroids are the “gold standard” of Sweet's syndrome treatment; potassium iodide or colchicine may also be used. Indomethacin, clofazimine, cyclosporine A and sulfones are the second-line drugs. PMID:24683399

  6. Castleman-Kojima disease (TAFRO syndrome) : a novel systemic inflammatory disease characterized by a constellation of symptoms, namely, thrombocytopenia, ascites (anasarca), microcytic anemia, myelofibrosis, renal dysfunction, and organomegaly : a status report and summary of Fukushima (6 June, 2012) and Nagoya meetings (22 September, 2012).

    PubMed

    Kawabata, Hiroshi; Takai, Kazue; Kojima, Masaru; Nakamura, Naoya; Aoki, Sadao; Nakamura, Shigeo; Kinoshita, Tomohiro; Masaki, Yasufumi

    2013-01-01

    Recently, a unique clinicopathologic variant of multicentric Castleman's disease (MCD) has been identified in Japan. This disease is characterized by a constellation of symptoms, as listed in the title, and multiple lymphadenopathy of mild degree with a pathologic diagnosis of atypical CD, often posing diagnostic and therapeutic problems for pathologists and hematologists, respectively. These findings suggest that this disease represents a novel clinical entity belonging to systemic inflammatory disorders with a background of immunological abnormality beyond the ordinal spectrum of MCD. To define this disorder more clearly, Japanese participants presented clinicopathologic data at the Fukushima and Nagoya meetings. Many of the patients presented by the participants were significantly accompanied by a combination of thrombocytopenia, ascites (anasarca), pleural effusions, microcytic anemia, fever, myelofibrosis, renal dysfunction, and organomegaly (TAFRO). Multiple lymphadenopathies were generally of mild degree, less than 1.5 cm in diameter, and consistently featured the histopathology of mixed- or less hyaline vascular-type CD. Autoantibodies were often detected. However, this disease did not fulfill the diagnostic criteria for well-known autoimmune diseases including systemic lupus erythematosus. Castleman-Kojima disease and TAFRO syndrome (the favored clinical term) were proposed for this disease. The patients were sensitive to steroid and anti-interleukin-6 receptor antibody (tocilizumab), but some exhibited a deteriorated clinical course despite the treatment. The participants proposed a future nationwide survey and a Japanese consortium to facilitate further clinical and therapeutic studies of this novel disease. [J Clin Exp Hematop 53(1): 57-61, 2013].

  7. Sotos syndrome.

    PubMed

    Juneja, A; Sultan, A

    2011-12-01

    Sotos syndrome is a well-defined childhood overgrowth syndrome characterized by pre- and postnatal overgrowth, developmental delay, advanced bone age, and a typical facial gestalt including macrodolichocephaly with frontal bossing, frontoparietal sparseness of hair, apparent hypertelorism, downslanting palpebral fissures, and facial flushing. This report presents a case of Sotos syndrome in a 5½-year-old child. PMID:22169837

  8. Velocardiofacial Syndrome

    ERIC Educational Resources Information Center

    Gothelf, Doron; Frisch, Amos; Michaelovsky, Elena; Weizman, Abraham; Shprintzen, Robert J.

    2009-01-01

    Velocardiofacial syndrome (VCFS), also known as DiGeorge, conotruncal anomaly face, and Cayler syndromes, is caused by a microdeletion in the long arm of Chromosome 22. We review the history of the syndrome from the first clinical reports almost half a century ago to the current intriguing molecular findings associating genes from the…

  9. Dumping Syndrome

    MedlinePlus

    ... Disease Organizations​​ (PDF, 341 KB)​​​​​ Alternate Language URL Dumping Syndrome Page Content On this page: What is ... Nutrition Points to Remember Clinical Trials What is dumping syndrome? Dumping syndrome occurs when food, especially sugar, ...

  10. Down syndrome

    MedlinePlus

    Down syndrome is a genetic condition in which a person has 47 chromosomes instead of the usual 46. ... In most cases, Down syndrome occurs when there is an extra copy of chromosome 21. This form of Down syndrome is called trisomy 21. ...

  11. Oesophageal inflammatory paediatric chylothorax

    PubMed Central

    Aherne, Thomas; Cullen, Paul; Mortell, Alan; McGuinness, Jonathan

    2014-01-01

    Paediatric chylothoraces are rare, particularly outside the operative setting. Cases of spontaneous chylothorax are often demanding diagnostically and frequently associated with patient morbidity. We present a challenging case of paediatric chylothorax associated with inflammatory oesophageal perforation likely related to foreign body ingestion. PMID:24920516

  12. Sjögren´s syndrome in present.

    PubMed

    Feltsan, T; Stanko, P; Mracna, J

    2012-01-01

    Sjögren´s syndrome is a systemic autoimmune disease characterized by a reduced function of exocrine glands, mainly salivary and lacrimal glands based on chronic plasmocellular infiltration. Syndrome includes affection of glands in gastrointestinal system, respiratory apparatus, skin, and vaginal mucosa. I tis described separately as a primary Sjögren´s syndrome or together with other inflammatory rheumatic diseases as a secondary Sjögren´s syndrome. Advanced diagnostic is based mainly on serologic examinations. Treatment of patients reflects the form of Sjögren´s syndrome. Despite recent knowledge the treatment is rather symptomatic than causal (Ref. 12).

  13. [Inflammatory bowel diseases: an immunological approach].

    PubMed

    Sepúlveda, Sofía E; Beltrán, Caroll J; Peralta, Alexis; Rivas, Paola; Rojas, Néstor; Figueroa, Carolina; Quera, Rodrigo; Hermoso, Marcela A

    2008-03-01

    Inflammatory bowel diseases (IBD) are inflammatory diseases with a multifactorial component that involve the intestinal tract. The two relevant IBD syndromes are Crohn's disease (CD) and ulcerative colitis (UC). One factor involved in IBD development is a genetic predisposition, associated to NOD2/CARD15 and Toll-like receptor 4 (TLR4) polymorphisms that might favor infectious enterocolitis that is possibly associated to the development of IBD. The identification of specific immunologic alterations in IBD and their relationship to the etiology of the disease is a relevant research topic. The role of intra and extracellular molecules, such as transcription factors and cytokines that are involved in the inflammatory response, needs to be understood. The relevance of immunologic molecules that might drive the immune response to a T helper (Th) 1, Th 2 or the recently described Th 17 phenotype, has been demonstrated in animal models and clinical studies with IBD patients. CD and UC predominantly behave with a Th 1 and Th 2 immune phenotype, respectively. Recently, an association between CD and Th 17 has been reported. The knowledge acquired from immunologic and molecular research will help to develop accurate diagnostic methods and efficient therapies.

  14. Can Probiotics Cure Inflammatory Bowel Diseases?

    PubMed

    Korada, Siva Kumar; Yarla, Nagendra Sastry; Bishayee, Anupam; Aliev, Gjumrakch; Aruna Lakshmi, K; Arunasree, M K; Dananajaya, B L; Mishra, Vijendra

    2016-01-01

    Gastrointestinal (GI) disorders, especially microbial dysbiosis play role in several GI ailments such as irritable bowel syndrome, colorectal cancer, inflammatory bowel diseases, and antibiotic-associated diarrhoea. Role of inflammatory bowel disease (IBD) is multifactorial as it involves loss of maintaining intestinal epithelial barrier integrity, increased release of pro-inflammatory molecules, and microbial dysbiosis in gut microflora. Some specific pathogens also play a key role in the IBD development. The origin and causation are still in unfathomable condition and the exact root cause is unknown. Recently probiotic studies have been gaining importance because of their positive responses in their IBD experimental results. According to joint Food and Agricultural Organisation/World Health Organisation working group, probiotics are defined as live microorganisms which when administered in adequate amount confer health benefit on the host. These live beneficial microorganisms are considered helpful in improving gut colonization and perseverance thereby improves prophylactic effect. In the direction of IBD research, a number of studies are needed to standardize its methodology and its applicability on human usage. The particular review presents an overview of gut microflora and its impact on host health, types of IBD and existing therapies to treat this disorder, mechanism of several probiotic actions, role of probiotics in IBD prevention with their supporting evidences. PMID:26648465

  15. Refeeding syndrome.

    PubMed

    Fernández López, M T; López Otero, M J; Alvarez Vázquez, P; Arias Delgado, J; Varela Correa, J J

    2009-01-01

    Refeeding syndrome is a complex syndrome that occurs as a result of reintroducing nutrition (oral, enteral or parenteral) to patients who are starved or malnourished. Patients can develop fluid-balance abnormalities, electrolyte disorders (hypophosphataemia, hypokalaemia and hypomagnesaemia), abnormal glucose metabolism and certain vitamin deficiencies. Refeeding syndrome encompasses abnormalities affecting multiple organ systems, including neurological, pulmonary, cardiac, neuromuscular and haematological functions. Pathogenic mechanisms involved in the refeeding syndrome and clinical manifestations have been reviewed. We provide suggestions for the prevention and treatment of refeeding syndrome. The most important steps are to identify patients at risk, reintroduce nutrition cautiously and correct electrolyte and vitamin deficiencies properly.

  16. Follow-up in healthy schoolchildren and in adolescents with DOWN syndrome: psycho-environmental and genetic determinants of physical activity and its impact on fitness, cardiovascular diseases, inflammatory biomarkers and mental health; the UP&DOWN Study

    PubMed Central

    2014-01-01

    Background An objective diagnosis of sedentary behaviour as well as of the physical activity and fitness levels in youth and to better understand how lifestyle is associated with cardiovascular disease risk factors and other phenotypes is of clinical and public health interest, and might be informative for developing intervention studies focused on the promotion of physical activity in these population. The aim of this methodological paper is to describe the design and assessment in the UP&DOWN study. Methods/Design The UP&DOWN study is a multi-center follow-up design where 2225 Spanish primary and secondary schoolchildren from Cadiz and Madrid, respectively, as well as 110 Spanish adolescents with Down syndrome from Madrid and Toledo were recruited to be assessed. Nine main measurement categories are assessed: i) socio-demographic and early determinants; ii) environmental determinants; iii) physical activity and sedentary behaviour; iv) health-related fitness; v) blood pressure and resting heart rate; vi) mental health; vii) dietary patterns; viii) blood samples; and ix) genetic analysis. During the 3-yr follow-up study, socio-demographic and early determinants, and genetic analysis are only assessed in the first year. Blood sampling is assessed in the first year and the third year (2nd follow-up), and all the other measurements are assessed every year. Discussion The findings of the UP&DOWN study may help the Health Information Systems and policy makers to identify the target population for primary prevention and health promotion policies, and to develop and test preventive strategies. Moreover, these data will allow following the trends at population level, as well as to modify/adapt/create new evidence-based physical activity guidelines at national level. The findings will also serve as a scientific platform for interventional studies. PMID:24761982

  17. [Acquired inflammatory neuropathies in children and their therapy].

    PubMed

    Kaciński, M

    2001-01-01

    Neuropathies where there is an association with acquired peripheral nerves dysfunction and inflammation include inflammatory neuropathies (IN), as well as sequelae of vaccinations involving peripheral nerves. In a small portion of these diseases central nervous system is involved. In the years 1996-2000, among 22 children with acute flaccid paresis who were hospitalized in the Kraków Department of Paediatric Neurology, there were 16 patients with IN, including 13 with Guillain-Barré syndrome, single cases of Miller-Fisher syndrome, chronic inflammatory demyelinating polyneuropathy involving central nervous system and neuroborreliosis. Additionally, four children were hospitalized for optic neuritis. The author presents data on aetiology, electrophysiology and follow-up of these patients, as well as describes the management and outcome. Apart from their cognitive and practical value, these data significantly correspond with the currently implemented program of poliomyelitis eradication.

  18. Medicinal agents and metabolic syndrome.

    PubMed

    Rubio-Ruiz, M E; El Hafidi, M; Pérez-Torres, I; Baños, G; Guarner, V

    2013-01-01

    The definition of the Metabolic Syndrome (MS) has encountered difficulty in reaching a universal consensus although there exists an agreement of its main pathologies which are hypertension, obesity, dyslipidemia, insulin resistance, inflammation and renal damage. The prevalent opinion is that three of those alterations may define the syndrome. The incidence of the MS has increased globally, particularly in the last few years, to the point of being regarded as an epidemic. The treatment of the MS can be approached from different angles, since it may be a multifaceted health problem. A healthy lifestyle, which means the practice of regular exercise is suggested to MS patients. Increasing physical activity has anti-inflammatory effects since there is an inverse association of physical activity and inflammatory biomarker concentrations. An adequate diet is recommended, such as the Mediterranean, which contains fish, tomatoes, garlic, red peppers, olive oil and includes red wine, that is, antioxidants and non-saturated oils. There are also the traditional herbal preparations, used in the alternative medicine. Several therapeutic tools can be used; the most common are the pharmaceutical products to deal with obesity, hypertension, dyslipidemias, diabetes and inflammation. In addition several pharmacological therapies such as non steroidal anti-inflammatory drugs are recommended. Recently new mechanisms of action of statins, fibrates, metformin and thiazolidinediones have demonstrated their anti-inflammatory effect and potential use to treat MS.

  19. Serotonin Syndrome

    PubMed Central

    Volpi-Abadie, Jacqueline; Kaye, Adam M.; Kaye, Alan David

    2013-01-01

    Background Serotonin syndrome is a potentially life-threatening syndrome that is precipitated by the use of serotonergic drugs and overactivation of both the peripheral and central postsynaptic 5HT-1A and, most notably, 5HT-2A receptors. This syndrome consists of a combination of mental status changes, neuromuscular hyperactivity, and autonomic hyperactivity. Serotonin syndrome can occur via the therapeutic use of serotonergic drugs alone, an intentional overdose of serotonergic drugs, or classically, as a result of a complex drug interaction between two serotonergic drugs that work by different mechanisms. A multitude of drug combinations can result in serotonin syndrome. Methods This review describes the presentation and management of serotonin syndrome and discusses the drugs and interactions that can precipitate this syndrome with the goal of making physicians more alert and aware of this potentially fatal yet preventable syndrome. Conclusion Many commonly used medications have proven to be the culprits of serotonin syndrome. Proper education and awareness about serotonin syndrome will improve the accuracy of diagnosis and promote the institution of the appropriate treatment that may prevent significant morbidity and mortality. PMID:24358002

  20. Inflammatory mechanisms of endometritis.

    PubMed

    Woodward, E M; Troedsson, M H T

    2015-07-01

    Transient post breeding endometritis is a normal physiological reaction in the mare, as it is believed that an inflammatory response is necessary for the effective removal of contaminating bacteria and excess spermatozoa introduced into the uterus. While most mares can clear endometritis within a reasonable amount of time, persistent endometritis caused by either bacteria or spermatozoa can threaten the success of a pregnancy. A subpopulation of mares is susceptible to persistent endometritis, and these mares are a concern in equine reproductive medicine. Research has identified several factors that contribute to susceptibility; however, the exact mechanisms of the progression of the disease are still being elucidated. Current research focuses on endometrial gene expression during endometritis in an attempt to understand the timing of specific inflammatory processes involved with the development of susceptibility to persistent endometritis. With an increased understanding of the mechanisms involved with the disease, current treatments can be improved upon, and new treatments can be developed to target affected pathways. PMID:25537084

  1. Keratoconus: an inflammatory disorder?

    PubMed Central

    Galvis, V; Sherwin, T; Tello, A; Merayo, J; Barrera, R; Acera, A

    2015-01-01

    Keratoconus has been classically defined as a progressive, non-inflammatory condition, which produces a thinning and steepening of the cornea. Its pathophysiological mechanisms have been investigated for a long time. Both genetic and environmental factors have been associated with the disease. Recent studies have shown a significant role of proteolytic enzymes, cytokines, and free radicals; therefore, although keratoconus does not meet all the classic criteria for an inflammatory disease, the lack of inflammation has been questioned. The majority of studies in the tears of patients with keratoconus have found increased levels of interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α), and matrix metalloproteinase (MMP)-9. Eye rubbing, a proven risk factor for keratoconus, has been also shown recently to increase the tear levels of MMP-13, IL-6, and TNF-α. In the tear fluid of patients with ocular rosacea, IL-1α and MMP-9 have been reported to be significantly elevated, and cases of inferior corneal thinning, resembling keratoconus, have been reported. We performed a literature review of published biochemical changes in keratoconus that would support that this could be, at least in part, an inflammatory condition. PMID:25931166

  2. [Inflammatory abdominal aortic aneurysm].

    PubMed

    Ziaja, K; Sedlak, L; Urbanek, T; Kostyra, J; Ludyga, T

    2000-01-01

    The reported incidence of inflammatory abdominal aortic aneurysm (IAAA) is from 2% to 14% of patients with abdominal aortic aneurysm and the etiology of this disease is still discussed--according to the literature several pathogenic theories have been proposed. From 1992 to 1997 32 patients with IAAA were operated on. The patients were mostly symptomatic--abdominal pain was present in 68.75% cases, back pain in 31.25%, fever in 12.5% and weight loss in 6.25% of the operated patients. In all the patients ultrasound examination was performed, in 4 patients CT and in 3 cases urography. All the patients were operated on and characteristic signs of inflammatory abdominal aortic aneurysm like: thickened aortic wall, perianeurysmal infiltration or retroperitoneal fibrosis with involvement of retroperitoneal structures were found. In all cases surgery was performed using transperitoneal approach; in three cases intraoperatively contiguous abdominal organs were injured, which was connected with their involvement into periaortic inflammation. In 4 cases clamping of the aorta was done at the level of the diaphragmatic hiatus. 3 patients (9.37%) died (one patient with ruptured abdominal aortic aneurysm). Authors present diagnostic procedures and the differences in the surgical tactic, emphasizing the necessity of the surgical therapy in patients with inflammatory abdominal aortic aneurysm.

  3. Genetics Home Reference: Aicardi-Goutieres syndrome

    MedlinePlus

    ... J. Aicardi-Goutieres syndrome and related phenotypes: linking nucleic acid metabolism with autoimmunity. Hum Mol Genet. 2009 Oct ... PubMed Central Rigby RE, Leitch A, Jackson AP. Nucleic acid-mediated inflammatory diseases. Bioessays. 2008 Sep;30(9): ...

  4. Overgrowth Syndromes.

    PubMed

    Edmondson, Andrew C; Kalish, Jennifer M

    2015-09-01

    Numerous multiple malformation syndromes associated with pathologic overgrowth have been described and, for many, their molecular bases elucidated. This review describes the characteristic features of these overgrowth syndromes, as well as the current understanding of their molecular bases, intellectual outcomes, and cancer predispositions. We review syndromes such as Sotos, Malan, Marshall-Smith, Weaver, Simpson-Golabi-Behmel, Perlman, Bannayan-Riley-Ruvalcaba, PI3K-related, Proteus, Beckwith-Wiedemann, fibrous dysplasia, Klippel-Trenaunay-Weber, and Maffucci. PMID:27617124

  5. Overgrowth Syndromes

    PubMed Central

    Edmondson, Andrew C.; Kalish, Jennifer M.

    2015-01-01

    Numerous multiple malformation syndromes associated with pathologic overgrowth have been described and, for many, their molecular bases elucidated. This review describes the characteristic features of these overgrowth syndromes, as well as the current understanding of their molecular bases, intellectual outcomes, and cancer predispositions. We review syndromes such as Sotos, Malan, Marshall–Smith, Weaver, Simpson–Golabi–Behmel, Perlman, Bannayan–Riley–Ruvalcaba, PI3K-related, Proteus, Beckwith–Wiedemann, fibrous dysplasia, Klippel–Trenaunay–Weber, and Maffucci. PMID:27617124

  6. Monogenic Autoinflammatory Syndromes: State of the Art on Genetic, Clinical, and Therapeutic Issues

    PubMed Central

    Costa, Luisa; Atteno, Mariangela; Compagnone, Adele; Caso, Paolo; Frediani, Bruno; Galeazzi, Mauro; Punzi, Leonardo

    2013-01-01

    Monogenic autoinflammatory syndromes (MAISs) are caused by innate immune system dysregulation leading to aberrant inflammasome activation and episodes of fever and involvement of skin, serous membranes, eyes, joints, gastrointestinal tract, and nervous system, predominantly with a childhood onset. To date, there are twelve known MAISs: familial Mediterranean fever, tumor necrosis factor receptor-associated periodic syndrome, familial cold urticaria syndrome, Muckle-Wells syndrome, CINCA syndrome, mevalonate kinase deficiency, NLRP12-associated autoinflammatory disorder, Blau syndrome, early-onset sarcoidosis, PAPA syndrome, Majeed syndrome, and deficiency of the interleukin-1 receptor antagonist. Each of these conditions may manifest itself with more or less severe inflammatory symptoms of variable duration and frequency, associated with findings of increased inflammatory parameters in laboratory investigation. The purpose of this paper is to describe the main genetic, clinical, and therapeutic aspects of MAISs and their most recent classification with the ultimate goal of increasing awareness of autoinflammation among various internal medicine specialists. PMID:24282415

  7. Association of Enterotoxigenic Bacteroides fragilis Infection with Inflammatory Diarrhea

    PubMed Central

    Sears, Cynthia L.; Islam, Salequl; Saha, Amit; Arjumand, Maleka; Alam, Nur Haque; Faruque, A. S. G.; Salam, M. A.; Shin, Jai; Hecht, David; Weintraub, Andrej; Sack, R. Bradley; Qadri, Firdausi

    2011-01-01

    Background Diarrheal illnesses remain a leading cause of morbidity and mortality globally, with increasing recognition of long-term sequelae, including postinfectious irritable bowel syndrome and growth faltering, as well as cognitive deficits in children. Identification of specific etiologic agents is often lacking. In vitro and in vivo data suggest that enterotoxigenic Bacteroides fragilis (ETBF) may contribute to the burden of colonic inflammatory diarrheal disease. The study goal was to investigate the pathogenesis of ETBF diarrheal illnesses. Methods We performed an observational study of children and adults with acute diarrheal illnesses in Dhaka, Bangladesh, from January 2004 through November 2005, to define the clinical presentation, intestinal inflammatory responses, and systemic and intestinal antibody responses to ETBF. Other enteric pathogens were also evaluated. Results ETBF was identified to cause a clinical syndrome with marked abdominal pain and nonfebrile inflammatory diarrhea in both children (age, >1 year) and adults. Fecal leukocytes, lactoferrin, and proinflammatory cytokines (interleukin 8, tumor necrosis factor–α)—as well as B. fragilis toxin systemic antitoxin responses—increased rapidly in ETBF-infected patients. Evidence of intestinal inflammation often persisted for at least 3 weeks, despite antibiotic therapy. Conclusions ETBF infection is a newly recognized cause of inflammatory diarrhea in children and adults. Future studies are needed to evaluate the role of ETBF in persistent colonic inflammation and other morbid sequelae of acute diarrheal disease. PMID:18680416

  8. [Cardiac complications in a metamizole-induced type I Kounis syndrome].

    PubMed

    Juste, Jose F Martínez; Garces, Tomas Ruiz; Enguita, Rafael Gonzalez; Blasco, Pedro Cia; Trallero, Jara Altemir

    2016-01-01

    Kounis syndrome is defined as the coincidental occurrence of allergic reaction and acute coronary syndrome secondary to vasospasm. Anti-inflammatory drugs are included as one of the multiple causes. Current data available about this syndrome come from case reports. We present the case of a patient who suffered Kounis syndrome with cardiogenic shock and asystole after intravenous infusion of Metamizole, and in which no lesions were observed in coronariography.

  9. Cardiac complications in a metamizole-induced type I Kounis syndrome.

    PubMed

    Juste, Jose F Martínez; Garces, Tomas Ruiz; Enguita, Rafael Gonzalez; Blasco, Pedro Cia; Trallero, Jara Altemir

    2016-01-01

    Kounis syndrome is defined as the coincidental occurrence of allergic reaction and acute coronary syndrome secondary to vasospasm. Anti-inflammatory drugs are included as one of the multiple causes. Current data available about this syndrome come from case reports. We present the case of a patient who suffered Kounis syndrome with cardiogenic shock and asystole after intravenous infusion of Metamizole, and in which no lesions were observed in coronariography.

  10. A case report with Fitz-Hugh-Curtis syndrome, what does it mean?

    PubMed

    Muschart, X

    2015-10-01

    Fitz-Hugh-Curtis (FHC) syndrome, also known as acute perihepatitis, was discovered in 1930 and is a rare disorder characterised by inflammation of the peritoneum and the tissues surrounding the liver. This syndrome can arise as a potential complication from a pelvic inflammatory disease caused by Neisseria gonorrhoeae or Chlamydia trachomatis. This syndrome is not well known in the medical community and is often underdiagnosed. In this case report, we revisit FHC syndrome, particularly its noninvasive diagnosis and complications. PMID:26743574

  11. Therapies aimed at the gut microbiota and inflammation: antibiotics, prebiotics, probiotics, synbiotics, anti-inflammatory therapies.

    PubMed

    Quigley, Eamonn M M

    2011-03-01

    Several recent observations have raised the possibility that disturbances in the gut microbiota and/or a low-grade inflammatory state may contribute to symptomatology and the etiology of irritable bowel syndrome (IBS). Consequent on these hypotheses, several therapeutic categories have found their way into the armamentarium of those who care for IBS sufferers. These agents include probiotics, prebiotics, antibiotics, and anti-inflammatory agents.

  12. Chronic inflammatory systemic diseases

    PubMed Central

    Straub, Rainer H.; Schradin, Carsten

    2016-01-01

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

  13. [Chronic prostatitis with chronic pelvic pain syndrome].

    PubMed

    Balvocius, Antanas

    2002-01-01

    Almost 10% of the adult male population suffer from prostatitis. The International Prostatitis Collaborative Network has devised and validated a clinically useful classification of prostatitis that urologists and primary care clinicians will find helpful. According to this schema, chronic bacterial prostatitis is clearly an infectious disease, and patients with chronic prostatitis associated with chronic pelvic pain syndrome can have either inflammatory or noninflammatory disease. Chronic bacterial prostatitis is uncommon, chronic nonbacterial prostatitis (CPPS) is extremely common. Antibiotic therapy is indicated in management of chronic bacterial prostatitis and inflammatory chronic pelvic pain syndrome. Fluoroquinolones are safe and effective in managing chronic bacterial prostatitis. Based on literature, noninflammatory chronic pelvic pain syndrome can be treated using adrenergic blockade, analgesic, tricyclic antidepressants, benzodiazepie, physical therapy. PMID:12556633

  14. Seckel syndrome: an overdiagnosed syndrome.

    PubMed Central

    Thompson, E; Pembrey, M

    1985-01-01

    Five children in whom a diagnosis of Seckel syndrome had previously been made were re-examined in the genetic unit. One child had classical Seckel syndrome, a sib pair had the features of the syndrome with less severe short stature, and in two children the diagnosis was not confirmed. Seckel syndrome is only one of a group of low birth weight microcephalic dwarfism and careful attention should be paid to fulfillment of the major criteria defined by Seckel before the diagnosis is made. There remains a heterogeneous group of low birth weight microcephalic dwarfism yet to be defined. Images PMID:4040172

  15. Marfan Syndrome

    MedlinePlus

    ... Connective tissue helps support all parts of your body. It also helps control how your body grows and develops. Marfan syndrome most often affects ... A mutation, or change, in the gene that controls how the body makes fibrillin causes Marfan syndrome. Fibrillin is a ...

  16. Myelodysplastic Syndromes

    MedlinePlus

    ... your body, the white blood cells that fight infections, and the platelets that help with blood clotting. If you have a myelodysplastic syndrome, the stem cells do not mature into healthy blood cells. ... anemia, or easy bleeding. Myelodysplastic syndromes often do ...

  17. Brown's syndrome.

    PubMed

    Wilson, M E; Eustis, H S; Parks, M M

    1989-01-01

    Brown's syndrome is a well-recognized clinical disorder of ocular motility manifesting most notably a restriction of active and passive elevation in adduction. The original name, "superior oblique tendon sheath syndrome," is no longer appropriate, since it has been shown that the tissue surrounding the anterior superior oblique tendon is blameless as a restrictive force. "True" and "simulated" as descriptive modifiers should also be discarded, as they relate to the disproven sheath concept. Brown's syndrome occurs as a congenital or acquired, constant or intermittent condition; the common link is restriction of free movement through the trochlea pulley mechanism. The various etiologic theories are reviewed and the spectrum of medical and surgical treatments are described and evaluated. Evidence suggests that subtypes of Brown's syndrome lie on a single continuum and that spontaneous resolution occurs in each group, probably more often than previously recognized. A simplified classification scheme is encouraged and possible future directions in Brown's syndrome research are introduced.

  18. Turner's syndrome.

    PubMed

    Ranke, M B; Saenger, P

    2001-07-28

    Before chromosomal analysis became available, the diagnosis of Turner's syndrome was based on the characteristics independently described by Otto Ullrich and Henry Turner, such as short stature, gonadal dysgenesis, typical, visible dysmorphic stigmata, and abnormalities in organs, which present in individuals with a female phenotype. Today, Turner's syndrome or Ullrich-Turner's syndrome may be defined as the combination of characteristic physical features and complete or part absence of one of the X chromosomes, frequently accompanied by cell-line mosaicism. The increasing interest in Turner's syndrome over the past two decades has been motivated both by the quest for a model by which the multi-faceted features of this disorder can be understood, and the endeavour to provide life-long support to the patient. New developments in research allow patients with Turner's syndrome to have multidisciplinary care.

  19. Wells Syndrome with Multiorgan Involvement Mimicking Hypereosinophilic Syndrome.

    PubMed

    Carlesimo, M; Fidanza, L; Mari, E; Feliziani, G; Narcisi, A; De Marco, G; Bartolazzi, A; Camplone, G

    2009-09-12

    Eosinophil-associated diseases represent a spectrum of heterogeneous disorders, where blood and cutaneous eosinophilia is the most important feature and eosinophils are the principal cause of cutaneous lesions. These diseases show some similarities in the clinical features but also many distinctive characteristics [Saurat et al., Dermatologia e malattie sessualmente trasmesse, Milano, Masson, 2000]. Wells syndrome is one of these disorders and is an uncommon recurrent inflammatory dermatosis, rarely associated to signs and symptoms of multiple organ involvement [Arch Dermatol 2006;142:1157-1161]. Hypereosinophilic syndrome, in contrast, constitutes a group of idiopathic disorders characterized by blood eosinophilia for at least 6 months, associated with single or multiple organ system dysfunction [Arch Dermatol 2006;142:1157-1161]. Clinically atypical Wells syndrome with multiorgan involvement is reported here. A correct diagnosis is difficult in this case, but clinical and histopathological features are compatible with this diagnosis. The reported condition likely represents a borderline hypereosinophilic disease, in which clinical features of both hypereosinophilic syndrome and Wells syndrome are present.

  20. Inflammatory Bowel Disease

    PubMed Central

    Corridoni, Daniele; Arseneau, Kristen O.; Cominelli, Fabio

    2014-01-01

    Inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), are chronic, relapsing inflammatory condition of the gastrointestinal tract. CD and UC have distinct pathologic and clinical characteristics and despite the extensive amount of research conducted over the past decades, their pathogenesis remains still poorly understood. So far, the accepted dogma is that IBD results from dysregulated mucosal immune response to environmental factors in genetical susceptible hosts. Various components are implicated in the pathogenesis of IBD, including genetic susceptibility, environmental and microbial factors, intestinal epithelial cells and components of innate and adaptive immune system. Given the complexity of IBD, several different animal models of IBD have been developed during the last years. Animal models are very important tools to study the involvement of various factors in the pathogenesis of IBD and, importantly, to test new therapeutic options. This review examines some of the key components that have been found to be closely associated to IBD and describe the distinct features of some of the most important IBD models. PMID:24938525

  1. Idiopathic Inflammatory Myopathies

    PubMed Central

    Barohn, Richard J.; Amato, Anthony

    2014-01-01

    The idiopathic inflammatory myopathies (IIM) consist of rare heterogenous autoimmune disorders that present with marked proximal and symmetric muscle weakness, except for distal and asymmetric weakness in inclusion body myositis (IBM). Besides frequent creatine kinase (CK) elevation, the electromyogram confirms the presence of an irritative myopathy. Extramuscular involvement affects a significant number of cases with interstitial lung disease (ILD), cutaneous in dermatomyositis (DM), systemic or joint manifestations and increased risk of malignancy especially in DM. Myositis specific autoantibodies influence phenotype of the IIM. Jo-1 antibodies are frequently associated with ILD and the newly described HMG-CoA reductase antibodies are characteristic of autoimmune necrotizing myopathy (NM). Muscle pathology ranges from inflammatory exudates of variable distribution, to intact muscle fiber invasion, necrosis, phagocytosis and in the case of IBM rimmed vacuoles and protein deposits. Despite many similarities, the IIM are a quite heterogeneous from the histopathological and pathogenetic standpoints in addition to some clinical and treatment-response difference. The field has witnessed significant advances in our understanding of pathophysiology and treatment of these rare disorders. In this review, we focus on DM, polymyositis (PM) and NM and examine current and promising therapies. The reader interested in more details on IBM is referred to the corresponding chapter in this issue. PMID:25037081

  2. Inflammatory and glandular skin disease in pregnancy.

    PubMed

    Yang, Catherine S; Teeple, Mary; Muglia, Jennie; Robinson-Bostom, Leslie

    2016-01-01

    A switch from cell-mediated to humoral immunity (helper T 1 [Th1] to helper T 2 [Th2] shift) during gestation plays a key role in placental immune tolerance. As a result, skin diseases that are Th2 mediated often worsen, whereas skin diseases that are Th1 mediated often improve during gestation. Also, due to fluctuations in glandular activity, skin diseases involving sebaceous and eccrine glands may flare, whereas those involving apocrine glands may improve during pregnancy. Despite these trends, inflammatory and glandular skin diseases do not always follow the predicted pattern, and courses are often diverse. We review the gestational course of inflammatory skin diseases, such as atopic dermatitis (atopic eruption of pregnancy), psoriasis, impetigo herpetiformis, urticaria, erythema annulare centrifugum, pityriasis rosea, sarcoidosis, Sweet syndrome, and erythema nodosum, as well as glandular skin diseases, including acne vulgaris, acne rosacea, perioral dermatitis, hidradenitis suppurativa, Fox-Fordyce disease, hyperhidrosis, and miliaria. For each of these diseases, we discuss the pathogenesis, clinical presentation, and management with special consideration for maternal and fetal safety. PMID:27265071

  3. Diagnosis and classification of idiopathic inflammatory myopathies.

    PubMed

    Lundberg, I E; Miller, F W; Tjärnlund, A; Bottai, M

    2016-07-01

    The idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of diseases, collectively termed myositis, sharing symptoms of muscle weakness, fatigue and inflammation. Other organs are frequently involved, supporting the notion that these are systemic inflammatory diseases. The IIMs can be subgrouped into dermatomyositis, polymyositis and inclusion body myositis. The myositis-specific autoantibodies (MSAs) identify other and often more distinct clinical phenotypes, such as the antisynthetase syndrome with antisynthetase autoantibodies and frequent interstitial lung disease and anti-SRP and anti-HMGCR autoantibodies that identify necrotizing myopathy. The MSAs are important both to support myositis diagnosis and to identify subgroups with different patterns of extramuscular organ involvement such as interstitial lung disease. Another cornerstone in the diagnostic procedure is muscle biopsy to identify inflammation and to exclude noninflammatory myopathies. Treatment effect and prognosis vary by subgroup. To develop new and better therapies, validated classification criteria that identify distinct subgroups of myositis are critical. The lack of such criteria was the main rationale for the development of new classification criteria for IIMs, which are summarized in this review; the historical background regarding previous diagnostic and classification criteria is also reviewed. As the IIMs are rare diseases with a prevalence of 10 in 100 000 individuals, an international collaboration was essential, as was the interdisciplinary effort including experts in adult and paediatric rheumatology, neurology, dermatology and epidemiology. The new criteria have been developed based on data from more than 1500 patients from 47 centres worldwide and are based on clinically easily available variables. PMID:27320359

  4. Histiocytoid Sweet’s syndrome in a patient with myelodsyplastic syndrome: report and review of the literature

    PubMed Central

    Shalaby, Michael M.; Riahi, Ryan R.; Rosen, Les B.; Soine, Erik J.

    2016-01-01

    The neutrophilic dermatoses are a group of disorders characterized by skin lesions for which histological examination reveals intense epidermal and/or dermal inflammatory infiltrates composed primarily of neutrophils without evidence of infection. The myelodysplastic syndromes consist of a heterogeneous group of malignant hematopoietic stem cell disorders characterized by dysplastic and inadequate blood cell production with a variable risk of transformation to acute leukemia. Rarely, histiocytoid Sweet’s syndrome occurring in patients with myelodysplastic syndrome has been described. We present a case of a 66-year-old woman with a history of myelodysplastic syndrome who developed histiocytoid Sweet’s syndrome. We also review the literature and characterize patients with myelodysplastic syndrome who have developed histiocytoid Sweet’s syndrome. PMID:26937301

  5. [Differential diagnosis of polyarthritis pain syndrome of the locomotor apparatus].

    PubMed

    Menninger, H

    1998-02-28

    Widespread pain syndromes of the musculoskeletal system present to general practitioners, internists, neurologists and orthopedic surgeons every day. The syndromes may result both from organic diseases (inflammatory joint diseases, rheumatic manifestations of organ diseases) as well as dysfunctional syndromes, the latter including mainly biomechanically induced syndromes and fibromyalgia. The approach is predominantly clinically oriented and requires laboratory means or technical procedures only in a limited extend. The duration of history, the recognition of synovitis and of myofascial trigger points or of integumental tender points allow in most patients to achieve appropriate diagnostic criteria.

  6. [A 38 years old female with inflammatory myofibroblastic tumor and lactic acidosis].

    PubMed

    Gorham, J; Liberale, G; Haydar, H Nasser; De Saint Aubain, N; Meert, A P

    2016-01-01

    Inflammatory myofibroblastic tumors (IMT) are rare tumors. They were originally described in the lung, but they have been now observed in many others locations, mainly abdominal and pelvic. These tumors are usually benign but their recurrent nature and the presence of an abnormality of chromosome band 2p23 in some of them, suggest that some lesions form a true tumor entity. Surgical excision as complete as possible is the gold standard treatment. We report the case of a 38 years old female, who presented a recurrent metastasizing inflammatory myofibroblastic tumor causing lactic acidosis and other biological abnormalities such as hypercalcemia, hypoalbuminemia, hypoglycemia, disseminated intravascular coagulation and inflammatory syndrome. PMID:27487696

  7. Neurocutaneous syndromes.

    PubMed

    Klar, Nitasha; Cohen, Bernard; Lin, Doris D M

    2016-01-01

    Neurocutaneous syndromes (or phakomatoses) are a diverse group of congenital disorders that encompass abnormalities of neuroectodermal and, sometimes, mesodermal development, hence commonly involving the skin, eye, and central nervous system. These are often inherited conditions and typically present in early childhood or adolescence. Some of the abnormalities and clinical symptoms may, however, be progressive, and there is an increased risk of neoplastic formation in many of the syndromes. As a group, neurocutaneous syndromes are characterized by distinctive cutaneous stigmata and neurologic symptomology, the latter often representing the most devastating and debilitating features of these diseases. Many of these syndromes are markedly heterogeneous in nature as they affect many organ systems. Given the incurable nature of these conditions and the broad spectrum of pathologies they comprise, treatments vary on a case-by-case basis and tend to be palliative rather than curative. With the advances in molecular genetics, however, greater understanding of biologic functions of the gene products and the correlative phenotypic expression is being attained, and this knowledge may guide future therapeutic developments. This chapter focuses on the cutaneous and neurologic pathology with emphasis on neuroimaging of selective neurocutaneous syndromes, including tuberous sclerosis, Sturge-Weber syndrome, Klippel-Trenaunay syndrome, ataxia-telangiectasia, and incontinentia pigmenti. PMID:27432683

  8. Kounis syndrome.

    PubMed

    Ntuli, P M; Makambwa, E

    2015-10-01

    Kounis syndrome is characterised by a group of symptoms that manifest as unstable vasospastic or non-vasospastic angina secondary to a hypersensitivity reaction. It was first described by Kounis and Zavras in 1991 as the concurrence of an allergic response with an anaphylactoid or anaphylactic reaction and coronary artery spasm or even myocardial infarction. Since then, this condition has evolved to include a number of mast cell activation disorders associated with acute coronary syndrome. There are many triggering factors, including reactions to multiple medications, exposure to radiological contrast media, poison ivy, bee stings, shellfish and coronary stents. In addition to coronary arterial involvement, Kounis syndrome comprises other arterial systems with similar physiologies, such as mesenteric and cerebral circulation resulting in ischaemia/infarction of the vital organs. The incidence of this condition is difficult to establish owing to the number of potential instigating factors and its relatively infrequent documentation in the literature.We report the case of an HIV-negative 39-year-old man with no coronary risk factors or family history of premature coronary artery disease, who developed Kounis syndrome after the administration of fluoroquinolone for dysuria. However, to the best of our knowledge,no data on the incidence and prevalence of Kounis syndrome in South Africa have ever been reported in the literature. The recent understanding of Kounis syndrome has led to the condition being classified into three syndrome variants.

  9. Inflammatory bowel disease.

    PubMed Central

    Van Rosendaal, G M

    1989-01-01

    An increasing number of options are available for the treatment of inflammatory bowel disease; the selection depends on the extent and severity of the disease. Experience with sulfasalazine and corticosteroids has led to a proliferation of 5-aminosalicylic acid (5-ASA) compounds and experimentation with alternative corticosteroid preparations. Given rectally 5-ASA is particularly effective in the treatment of distal ulcerative colitis, and experience is accumulating with several oral formulations. Metronidazole is useful in some cases, and immunosuppressive agents have a role in some patients with chronic refractory disease. A variety of measures, such as nutritional therapy, surgery and psychosocial support, are important elements of therapy. Further therapeutic innovations are expected as the etiology and pathogenesis are clarified. PMID:2568163

  10. Inflammatory Bowel Disease

    PubMed Central

    Kaser, Arthur; Zeissig, Sebastian; Blumberg, Richard S.

    2015-01-01

    Insights into inflammatory bowel disease (IBD) are advancing rapidly owing to immunologic investigations of a plethora of animal models of intestinal inflammation, ground-breaking advances in the interrogation of diseases that are inherited as complex genetic traits, and the development of culture-independent methods to define the composition of the intestinal microbiota. These advances are bringing a deeper understanding to the genetically determined interplay between the commensal microbiota, intestinal epithelial cells, and the immune system and the manner in which this interplay might be modified by relevant environmental factors in the pathogenesis of IBD. This review examines these interactions and, where possible, potential lessons from IBD-directed, biologic therapies that may allow for elucidation of pathways that are central to disease pathogenesis in humans. PMID:20192811

  11. Treatment of inflammatory myopathies

    PubMed Central

    Cordeiro, A C; Isenberg, D A

    2006-01-01

    Idiopathic inflammatory myopathies, notably polymyositis and dermatomyositis are comparatively uncommon diseases and few randomised, double blind placebo controlled trials have been done. Final validation of measures to assess outcome and response to treatment is awaited. Corticosteroids are an effective initial treatment, although rarely tested in randomised controlled trials. Unfortunately, not all patients respond to them and many develop undesirable side effects. There is thus a need for second line agents notably immunosuppressives or intravenous immunoglobulin. There are no defined guidelines or best treatment protocols agreed internationally and so the medical approach must be individualised, based on the severity of clinical presentation, disease duration, presence of extramuscular features, and prior therapy and contraindications to particular agents. There is still a significant percentage of non‐responders (around 25%) and clinical relapses. Novel therapeutic approaches are now directed towards cytokine modulation and the use of monoclonal antibodies targeting B and T cells. PMID:16822917

  12. Treatment of inflammatory myopathies.

    PubMed

    Cordeiro, A C; Isenberg, D A

    2006-07-01

    Idiopathic inflammatory myopathies, notably polymyositis and dermatomyositis are comparatively uncommon diseases and few randomised, double blind placebo controlled trials have been done. Final validation of measures to assess outcome and response to treatment is awaited. Corticosteroids are an effective initial treatment, although rarely tested in randomised controlled trials. Unfortunately, not all patients respond to them and many develop undesirable side effects. There is thus a need for second line agents notably immunosuppressives or intravenous immunoglobulin. There are no defined guidelines or best treatment protocols agreed internationally and so the medical approach must be individualised, based on the severity of clinical presentation, disease duration, presence of extramuscular features, and prior therapy and contraindications to particular agents. There is still a significant percentage of non-responders (around 25%) and clinical relapses. Novel therapeutic approaches are now directed towards cytokine modulation and the use of monoclonal antibodies targeting B and T cells.

  13. [Chronic inflammatory demyelinating polyradiculoneuropathy].

    PubMed

    Franques, J; Azulay, J-P; Pouget, J; Attarian, S

    2010-06-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a demyelinating chronic neuropathy of immune origin whose diagnosis is based upon clinical, biological and electrophysiological data; previously critical to the diagnosis the nerve biopsy is now restricted to the rare situations where accurate diagnosis cannot be reached using these data alone. CIDP are mainly idiopathic, but a few associated diseases must be sought for as they require specific attention. Such associated diseases must particularly be discussed when the manifestations are severe or resistant to immunomodulating or immunosuppressive agents. Indeed, idiopathic CIDP are usually responsive to these treatments. The effectiveness of these treatments is limited by the importance of the secondary axonal loss. The dependence or the resistance may sometimes justify the association of several immunomodulating treatments. A single randomized controlled trial support the use of cytotoxic drugs and none with rituximab.

  14. Inflammatory and toxic myopathies.

    PubMed

    Dalakas, M C

    1992-10-01

    The major advances in the immunopathogenesis and treatment of inflammatory myopathies, and the main criteria that distinguish polymyositis (PM) from dermatomyositis (DM) or inclusion-body myositis (IBM) are presented. The origin and implications of the amyloid and ubiquitin deposits found within the vacuolated fibers of patients with IBM are considered. The pathogenesis of human immunodeficiency virus (HIV) and human T-cell lymphotrophic virus (HTLV)-I-associated PM is presented, and the role of retroviruses in triggering PM, even in the absence of detectable viral genome within the muscle fibers, is discussed. In addition, three toxic myopathies with distinct morphologic, biochemical, or molecular characteristics, caused by zidovudine [azidothymidine (AZT) myopathy], the cholesterol-lowering-agent myopathy (CLAM), and the combination of blocking agents with corticosteroids are presented.

  15. Chronic inflammatory demyelinating polyradiculoneuropathy.

    PubMed

    Van den Bergh, Peter Y K; Rajabally, Yusuf A

    2013-06-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is the most common autoimmune neuropathy. The diagnosis depends on the clinical presentation with a progressive or relapsing course over at least 2 months and electrophysiological evidence of primary demyelination. Whereas typical CIDP is quite easily recognizable because virtually no other neuropathies present with both distal and proximal motor and sensory deficit, atypical CIDP, focal and multifocal variants in particular, may represent a difficult diagnostic challenge. CIDP very likely is an underdiagnosed condition as suggested also by a positive correlation between prevalence rates and sensitivity of electrophysiological criteria. Since no 'gold standard' diagnostic marker exists, electrophysiological criteria have been optimized to be at the same time as sensitive and as specific as possible. Additional supportive laboratory features, such as increased spinal fluid protein, MRI abnormalities of nerve segments, and in selected cases nerve biopsy lead to the correct diagnosis in the large majority of the cases. Objective clinical improvement following immune therapy is also a useful parameter to confirm the diagnosis. The pathogenesis and pathophysiology of CIDP remain poorly understood, but the available evidence for an inflammatory origin is quite convincing. Steroids, intravenous immunoglobulin (IVIG), and plasma exchange (PE) have been proven to be effective treatments. IVIG usually leads to rapid improvement, which is useful in severely disabled patients. Repeat treatment over regular time intervals for many years is often necessary. The effect of steroids is slower and the side-effect profile may be problematic, but they may induce disease remission more frequently than IVIG. An important and as of yet uncompletely resolved issue is the evaluation of long-term outcome to determine whether the disease is still active and responsive to treatment.

  16. Autoantibodies in inflammatory arthritis.

    PubMed

    Conigliaro, P; Chimenti, M S; Triggianese, P; Sunzini, F; Novelli, L; Perricone, C; Perricone, R

    2016-07-01

    Rheumatoid arthritis (RA) is a systemic chronic inflammatory disease characterized by extensive synovitis resulting in erosions of articular cartilage and marginal bone with joint destruction. The lack of immunological tolerance in RA represents the first step toward the development of autoimmunity. Susceptible individuals, under the influence of environmental factors, such as tobacco smoke, and silica exposure, develop autoimmune phenomena that result in the presence of autoantibodies. HLA and non-HLA haplotypes play a major role in determining the development of specific autoantibodies differentiating anti-citrullinated antibodies (ACPA)-positive and negative RA patients. Rheumatoid factor (RF) and ACPA are the serological markers for RA, and during the preclinical immunological phase, autoantibody titers increase with a progressive spread of ACPA antigens repertoire. The presence of ACPA represents an independent risk factor for developing RA in patients with undifferentiated arthritis or arthralgia. Moreover, anti-CarP antibodies have been identified in patients with RA as well as in individuals before the onset of clinical symptoms of RA. Several autoantibodies mainly targeting post-translational modified proteins have been investigated as possible biomarkers to improve the early diagnosis, prognosis and response to therapy in RA patients. Psoriatic arthritis (PsA) is distinguished from RA by infrequent positivity for RF and ACPA, together with other distinctive clinical features. Actually, specific autoantibodies have not been described. Recently, anti-CarP antibodies have been reported in sera from PsA patients with active disease. Further investigations on autoantibodies showing high specificity and sensibility as well as relevant correlation with disease severity, progression, and response to therapy are awaited in inflammatory arthritides.

  17. Hubris syndrome.

    PubMed

    Owen, David

    2008-08-01

    Hubris syndrome is associated with power, more likely to manifest itself the longer the person exercises power and the greater the power they exercise. A syndrome not to be applied to anyone with existing mental illness or brain damage. Usually symptoms abate when the person no longer exercises power. It is less likely to develop in people who retain a personal modesty, remain open to criticism, have a degree of cynicism or well developed sense of humour. Four heads of government in the last 100 years are singled out as having developed hubris syndrome: David Lloyd George, Margaret Thatcher, George W Bush and Tony Blair.

  18. [William's syndrome].

    PubMed

    Rubia Vila, Francisco José

    2007-01-01

    William's syndrome is of great interest to neurosclence as it is expected to help understand the genetic and neural mechanisms that underlie our cognitive systems. Although patients with this syndrome have moderate levels of learning disability, some of them, however, have superior skills in language, auditory memory, face recognition, empathy with others and a passion for music. The theory that best explains this syndrome is that the degeneration of the functions of the left hemisphere generates a compensation via an increase in the functions of the right hemisphere. PMID:18069600

  19. [DRESS syndrome].

    PubMed

    Adamcová, Monika; Šturdík, Igor; Koller, Tomáš; Payer, Juraj

    2016-04-01

    DRESS syndrome (Drug Rash with Eosinophilia and Systemic Symptoms) is severe drug-induced allergic-type reaction which occurs few days to weeks after taking a drug in a predisposed patient. Organ damage, eosinophilia and skin rash are typical at presentation. Corticotherapy is often necessary in severe cases. In this report we describe a case of 56-year old female with fever, elevated liver tests and skin rash. DRESS syndrome was diagnosed and allopurinol was indentified as a causative drug. Due to possible fatal outcome, DRESS syndrome should be considered in a differential diagnosis of all patients presenting with similar signs and symptoms. PMID:27250614

  20. Velocardiofacial syndrome.

    PubMed Central

    Pike, A. C.; Super, M.

    1997-01-01

    Velocardiofacial syndrome is a syndrome of multiple anomalies that include cleft palate, cardiac defects, learning difficulties, speech disorder and characteristic facial features. It has an estimated incidence of 1 in 5000. The majority of cases have a microdeletion of chromosome 22q11.2. The phenotype of this condition shows considerable variation, not all the principal features are present in each case. Identification of the syndrome can be difficult as many of the anomalies are minor and present in the general population. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:9497944

  1. LEOPARD Syndrome.

    PubMed

    Ghosh, Sudip Kumar; Majumdar, Biswajit; Rudra, Olympia; Chakraborty, Sougat

    2015-10-01

    LEOPARD syndrome (LS) is an autosomal dominantly inherited or sporadic disorder of variable penetrance and expressivity. The acronym LEOPARD stands for its cardinal clinical features including Lentigines, Electrocardiographic conduction abnormalities, Ocular hypertelorism, Pulmonary stenosis, Abnormalities of genitalia, Retardation of growth, and Deafness. We present herein a patient with LEOPARD syndrome and distinctive features. It was noteworthy that our patient presented with the concern of generalized lentiginosis and subsequent evaluation revealed that the patient had LEOPARD syndrome. In this report we would like to highlight the importance of detailed clinical examination and appropriate imaging in patients with multiple lentigines.

  2. [PATHOPHYSIOLOGY OF CARDIORENAL SYNDROME].

    PubMed

    Thervet, Éric

    2016-06-01

    The pathophysiology of cardiorenal syndromes (SCR) is becoming better understood. The traditional view was that the left ventricular systolic dysfunction leads to a decrease in renal blood flow. Although this mechanism still makes sense as a contributing factor to SCR, its role as the principal pathophysiological SCR component or even as essential hemodynamic underlying factor has been challenged by recent discoveries. Regarding hemodynamic, the role of increased venous pressure is more and more accepted as demonstrated by the increase in abdominal pressure. Moreover, the role of neurohormonal mechanisms is emphasized in particular through the autonomic nervous system, the renin angiotensin aldosterone system, arginine vasopressin, adenosine and inflammatory mediators. Abnormal endothelial function is also responsible for a worsening of lesions especially through the reduction of shear stress. Finally, atherosclerosis, proteinuria, anemia with iron metabolism modifications, the nutritional status and vitamin D deficiency as well as FGF23 changes may be important and could represent interesting new therapeutic approaches in patients with SCR. PMID:27538312

  3. Complex Regional Pain Syndrome.

    PubMed

    Ersoy, Hale; Pomeranz, Stephen J

    2016-01-01

    Complex regional pain syndrome (CRPS) is a neurological disorder producing peripheral neurogenic inflammatory process in hands and feet distal to injury, which may lead to severe disability. Symptoms are often out of proportion to the initiating event and not limited to a single peripheral nerve. There is no gold standard in diagnosis of this entity, and a multidisciplinary approach is necessary for proper diagnosis. Magnetic resonance imaging (MRI) is one of the most useful diagnostic modalities in early stages of CRPS (when clinical diagnosis is most difficult), the most desirable time to diagnose this disorder to expedite treatment and improve function. This article discusses MRI findings of CRPS, particularly in the early phase, and differential considerations. PMID:27518298

  4. Charcot foot syndrome.

    PubMed

    Jeffcoate, W J

    2015-06-01

    Charcot foot syndrome is an uncommon complication of diabetes but is potentially devastating in its consequences. Outcome is made worse by widespread professional ignorance leading to delayed diagnosis, but it is also hampered by lack of understanding of its causes and lack of treatments with proven effectiveness, other than offloading. There remains a desperate need for studies into its causes as well as comparative audit and trials designed to determine the best treatment for this difficult condition. Such work can probably only be effectively carried out through the establishment of multicentre networks. Nevertheless, improved understanding in recent years of the likely role of inflammatory pathways has raised awareness of the multiple ways in which the effects of neuropathy may be manifest in the development of the Charcot foot. This awareness is also leading to the realization that similar processes may conceivably contribute to the refractoriness of other foot diseases in diabetes, including both chronic unhealing ulcers and osteomyelitis.

  5. Co-morbidities in inflammatory dermatological diseases. Psoriasis, hidradenitis suppurativa, and cardiovascular risk factors.

    PubMed

    Miller, Iben M

    2015-09-01

    In conclusion, this thesis demonstrated an association between inflammatory dermatological diseases, i.e. psoriasis and hidradenitis suppurativa, and the metabolic syndrome putting these two patient groups at cardiovascular risk. Therefore, it is recommended as a minimum to screen hidradenitis and psoriasis patients attending in/outpatient clinics for the metabolic syndrome aimed at prevention of cardiovascular disease. The increased risk of metabolic syndrome adds to the range of well-known disease-related burdens e.g. the physical skin symptoms, the psychological impact thereof, and other co-morbidities, thus highlighting that both hidradenitis and psoriasis patients require general medical attention beyond the skin.

  6. Vitamin D in inflammatory diseases

    PubMed Central

    Wöbke, Thea K.; Sorg, Bernd L.; Steinhilber, Dieter

    2014-01-01

    Changes in vitamin D serum levels have been associated with inflammatory diseases, such as inflammatory bowel disease (IBD), rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis (MS), atherosclerosis, or asthma. Genome- and transcriptome-wide studies indicate that vitamin D signaling modulates many inflammatory responses on several levels. This includes (i) the regulation of the expression of genes which generate pro-inflammatory mediators, such as cyclooxygenases or 5-lipoxygenase, (ii) the interference with transcription factors, such as NF-κB, which regulate the expression of inflammatory genes and (iii) the activation of signaling cascades, such as MAP kinases which mediate inflammatory responses. Vitamin D targets various tissues and cell types, a number of which belong to the immune system, such as monocytes/macrophages, dendritic cells (DCs) as well as B- and T cells, leading to individual responses of each cell type. One hallmark of these specific vitamin D effects is the cell-type specific regulation of genes involved in the regulation of inflammatory processes and the interplay between vitamin D signaling and other signaling cascades involved in inflammation. An important task in the near future will be the elucidation of the regulatory mechanisms that are involved in the regulation of inflammatory responses by vitamin D on the molecular level by the use of techniques such as chromatin immunoprecipitation (ChIP), ChIP-seq, and FAIRE-seq. PMID:25071589

  7. Marfan Syndrome

    MedlinePlus

    Marfan syndrome is a disorder that affects connective tissue. Connective tissues are proteins that support skin, bones, blood vessels, and other organs. One of these proteins is fibrillin. A problem with the ...

  8. Reifenstein syndrome

    MedlinePlus

    ... with the gene will be affected. Every female child has a 50% chance of carrying the gene. Family history is important in determining risk factors. The syndrome is estimated to affect 1 in 99,000 people.

  9. Paraneoplastic Syndromes

    PubMed Central

    Stolinsky, David C.

    1980-01-01

    Neoplasms can produce a variety of remote effects on the host; these are referred to as paraneoplastic syndromes. The syndromes may affect any of the systems of the body, may precede or follow the diagnosis of the underlying neoplasm, and may or may not parallel the course of the neoplasm in severity. The diagnosis of and therapy for these syndromes can be challenging to a physician, but successful therapy may bring about worthwhile relief for the patient. In addition, the syndromes and the substances that cause them are sometimes useful in diagnosing and in following the course of certain neoplasms. Perhaps of greater importance, study of these remote effects of neoplasia may shed light on the nature of the neoplastic process itself. PMID:6990627

  10. Beals Syndrome

    MedlinePlus

    ... have many of the skeletal (bone) and aortic enlargement problems as people with Marfan syndrome, and treatments ... appearance to the top of the ear Aortic enlargement and/or mitral valve regurgitation (occasionally) People with ...

  11. Aase syndrome

    MedlinePlus

    Aase-Smith syndrome; Hypoplastic anemia - triphalangeal thumbs, Aase-Smith type ... Jones KL, Jones MC, Del Campo M, eds. Smith's Recognizable Patterns of Human Malformation . 7th ed. Philadelphia, ...

  12. Turner Syndrome

    MedlinePlus

    ... turnersyndrome. html • Eunice Kennedy Shriver National Institutes of Child Health & Human Development (NIH): www. nichd. nih. gov/ health/ topics/ Turner_ Syndrome. cfm • Mayo Clinic: www. mayoclinic. com/ health/ turner- ...

  13. Scheie syndrome

    MedlinePlus

    ... for families who have a child with Scheie syndrome, to help them understand the condition and possible treatments. Prenatal testing is available. Alternative Names Mucopolysaccharidosis type I S; MPS ...

  14. Potter syndrome

    MedlinePlus

    Potter phenotype ... In Potter syndrome, the primary problem is kidney failure. The kidneys fail to develop properly as the baby is ... kidneys normally produce the amniotic fluid (as urine). Potter phenotype refers to a typical facial appearance that ...

  15. Behcet's Syndrome

    MedlinePlus

    Behcet's syndrome is a disease that involves vasculitis, which is inflammation of the blood vessels. It causes problems in many parts of the body. The ... National Institute of Arthritis and Musculoskeletal and Skin Diseases

  16. Serotonin syndrome

    MedlinePlus

    ... Increased body temperature Loss of coordination Nausea Overactive reflexes Rapid changes in blood pressure Vomiting ... as confusion or hypomania Muscle spasms (myoclonus) Overactive reflexes ( ... Tremor Uncoordinated movements (ataxia) Serotonin syndrome ...

  17. Down Syndrome

    MedlinePlus

    ... or problems with their heart, stomach or eyes. Intelligence ranges from low normal to very retarded (slow ... a baby who has Down syndrome will be. Intelligence ranges from low normal to very retarded (slow ...

  18. Menkes syndrome

    MedlinePlus

    ... Menkes syndrome, cells in the body can absorb copper, but they are unable to release it. It ... makes it hard for the body to distribute copper in food from the intestines into the bloodstream ...

  19. Noonan syndrome

    MedlinePlus

    ... EKG , chest x-ray , or echocardiogram Hearing tests Growth hormone levels Genetic testing can help diagnose this syndrome. ... will suggest treatment to relieve or manage symptoms. Growth hormone has been used successfully to treat short height ...

  20. Hunter syndrome

    MedlinePlus

    Hunter syndrome is a disease in which long chains of sugar molecules (glycosaminoglycans, formerly called mucopolysaccharides ) are ... of the enzyme iduronate sulfatase. Without this enzyme, chains of sugar molecules build up in various body ...

  1. [Refeeding syndrome].

    PubMed

    Ševela, Stanislav; Novák, František; Kazda, Antonín; Brodská, Helena

    2016-01-01

    Despite being known more than 60 years, refeeding syndrome (RS) still bears many uncertainties. For example, its definition is not clear and definite, and the attitude to it varies from the complete neglect to over-prevention.The term "refeeding syndrome" refers to electrolyte and metabolic changes occurring in malnourished patients after the readministration of nutrition. These changes concern especially to phosphates and ions. Potassium, magnesium, naturism and fluids balance are involved. The changes lead to cell energetic metabolism and electric potential disturbances, with related clinical symptoms.Fully developed refeeding syndrome is quite rare; nevertheless it can be fatal for the patient. However, even its development can lead to many complications increasing the patient's morbidity and the length of stay in the hospital. Yet the refeeding syndrome is more or less predictable and if kept in mind also preventable.The aim of this article is to get the reader to know more about this metabolic phenomenon and possible attitudes towards it.

  2. Cushing's Syndrome

    MedlinePlus

    ... cause is long-term exposure to too much cortisol, a hormone that your adrenal gland makes. Sometimes, ... can cause your body to make too much cortisol. Cushing's syndrome is rare. Some symptoms are Upper ...

  3. Joubert Syndrome

    MedlinePlus

    ... Funding Information Research Programs Training & Career Awards Enhancing Diversity Find People About NINDS NINDS Joubert Syndrome Information ... News From NINDS | Find People | Training | Research | Enhancing Diversity Careers@NINDS | FOIA | Accessibility Policy | Contact Us | Privacy ...

  4. Malabsorption Syndromes

    MedlinePlus

    ... They often include chronic diarrhea, abnormal stools, weight loss, and gas. Your doctor may use lab, imaging, or other tests to make a diagnosis. Treatment of malabsorption syndromes depends on the cause.

  5. [Kabuki syndrome].

    PubMed

    Stankovics, J

    1995-08-20

    Kabuki syndrome is characterised by a peculiar face resembling the make-up of actors in Kabuki, the traditional Japanese theatre, postnatal growth deficiency, mild to moderate mental retardation, unusual dermatoglyphic patterns, and various skeletal and visceral anomalies. The author would like to draw attention to this less known condition in Hungary by a case-report of a 23 months old female patient with Kabuki syndrome. PMID:7651720

  6. [Fisher Syndrome and Bickerstaff Brainstem Encephalitis].

    PubMed

    Kuwabara, Satoshi

    2015-11-01

    Fisher syndrome has been regarded as a peculiar inflammatory neuropathy with ophthalmoplegia, ataxia, and areflexia, whereas Bickerstaff brainstem encephalitis has been considered a pure central nervous system disease characterized by ophthalmoplegia, ataxia, and consciousness disturbance. Both disorders share common features including preceding infection, albumin-cytological dissociation, and association with Guillain-Barré syndrome. The discovery of anti-GQ1b IgG antibodies further supports the view that the two disorders represent a single disease spectrum. The lesions in Fisher syndrome and Bickerstaff brainstem encephalitis are presumably determined by the expression of ganglioside GQ1b in the human peripheral and central nervous systems. Bickerstaff brainstem encephalitis is likely to represent a variant of Fisher syndrome with central nervous system involvement. PMID:26560952

  7. [Pseudolymphoma in patients with primary Sjogren's syndrome].

    PubMed

    Dabrowska, M; Jórasz, I; Duda-Król, W; Polubiec, A

    2001-08-01

    Sjögren's syndrome is an inflammatory autoimmune disease affecting primarily the exocrine glands. In the abscence of other autoimmune diseases it is classified as primary Sjögren's syndrome. Patients with primary syndrome have about 40 times higher relative risk of developing lymphoma then normal population, which offers a possibility to study malignant transformation's mechanisms in these patients. In the study we report a case of a woman with pseudolymphoma. The clinical diagnose used to be based on symptoms of proliferate disease, quetionnable histological evaluation and good response to steroids. Nowadays, applying advanced molecular techniques make it possible to diagnose lymphoma in labial salivary biopsy much earlier. It allows recognizing an incipient lymphoma in a group of patients with primary Sjögren's syndrome. Therefore so-called pseudolymphoma can usually be diagnosed as either benign or malignant lymphoproliferative lesions.

  8. Acute Respiratory Distress Syndrome as the Initial Clinical Manifestation of an Antisynthetase Syndrome.

    PubMed

    Kim, Seo-Hyun; Park, I-Nae

    2016-07-01

    Antisynthetase syndrome has been recognized as an important cause of autoimmune inflammatory myopathy in a subset of patients with polymyositis and dermatomyositis. It is associated with serum antibody to aminoacyl-transfer RNA synthetases and is characterized by a constellation of manifestations, including fever, myositis, interstitial lung disease, mechanic's hand-like cutaneous involvement, Raynaud phenomenon, and polyarthritis. Lung disease is the presenting feature in 50% of the cases. We report a case of a 60-year-old female with acute respiratory distress syndrome (ARDS), which later proved to be an unexpected and initial manifestation of anti-Jo-1 antibody-positive antisynthetase syndrome. The present case showed resolution of ARDS after treatment with high-dose corticosteroids. Given that steroids are not greatly beneficial in the treatment of ARDS, it is likely that the improvement of the respiratory symptoms in this patient also resulted from the prompt suppression of the inflammatory systemic response by corticosteroids. PMID:27433180

  9. Acute Respiratory Distress Syndrome as the Initial Clinical Manifestation of an Antisynthetase Syndrome

    PubMed Central

    Kim, Seo-Hyun

    2016-01-01

    Antisynthetase syndrome has been recognized as an important cause of autoimmune inflammatory myopathy in a subset of patients with polymyositis and dermatomyositis. It is associated with serum antibody to aminoacyl-transfer RNA synthetases and is characterized by a constellation of manifestations, including fever, myositis, interstitial lung disease, mechanic's hand-like cutaneous involvement, Raynaud phenomenon, and polyarthritis. Lung disease is the presenting feature in 50% of the cases. We report a case of a 60-year-old female with acute respiratory distress syndrome (ARDS), which later proved to be an unexpected and initial manifestation of anti-Jo-1 antibody–positive antisynthetase syndrome. The present case showed resolution of ARDS after treatment with high-dose corticosteroids. Given that steroids are not greatly beneficial in the treatment of ARDS, it is likely that the improvement of the respiratory symptoms in this patient also resulted from the prompt suppression of the inflammatory systemic response by corticosteroids. PMID:27433180

  10. Maladaptive immune and inflammatory pathways lead to cardiovascular insulin resistance.

    PubMed

    Aroor, Annayya R; McKarns, Susan; Demarco, Vincent G; Jia, Guanghong; Sowers, James R

    2013-11-01

    Insulin resistance is a hallmark of obesity, the cardiorenal metabolic syndrome and type 2 diabetes mellitus (T2DM). The progression of insulin resistance increases the risk for cardiovascular disease (CVD). The significance of insulin resistance is underscored by the alarming rise in the prevalence of obesity and its associated comorbidities in the Unites States and worldwide over the last 40-50 years. The incidence of obesity is also on the rise in adolescents. Furthermore, premenopausal women have lower CVD risk compared to men, but this protection is lost in the setting of obesity and insulin resistance. Although systemic and cardiovascular insulin resistance is associated with impaired insulin metabolic signaling and cardiovascular dysfunction, the mechanisms underlying insulin resistance and cardiovascular dysfunction remain poorly understood. Recent studies show that insulin resistance in obesity and diabetes is linked to a metabolic inflammatory response, a state of systemic and tissue specific chronic low grade inflammation. Evidence is also emerging that there is polarization of macrophages and lymphocytes towards a pro-inflammatory phenotype that contributes to progression of insulin resistance in obesity, cardiorenal metabolic syndrome and diabetes. In this review, we provide new insights into factors, such as, the renin-angiotensin-aldosterone system, sympathetic activation and incretin modulators (e.g., DPP-4) and immune responses that mediate this inflammatory state in obesity and other conditions characterized by insulin resistance.

  11. Neuropsychiatric manifestations in inflammatory neuropathies: A systematic review.

    PubMed

    Rajabally, Yusuf A; Seri, Stefano; Cavanna, Andrea E

    2016-06-01

    We conducted a systematic literature review on psychological and behavioral comorbidities in patients with inflammatory neuropathies. In Guillain-Barré syndrome (GBS), psychotic symptoms are reported during early stages in 30% of patients. Typical associations include mechanical ventilation, autonomic dysfunction, inability to communicate, and severe weakness. Anxiety and depression are frequent comorbidities. Anxiety may increase post-hospital admissions and be a predictor of mechanical ventilation. Posttraumatic stress disorder may affect up to 20% of ventilated patients. Sleep disturbances are common in early-stage GBS, affecting up to 50% of patients. In chronic inflammatory demyelinating polyradiculoneuropathy, memory and quality of sleep may be impaired. An independent link between depression and pretreatment upper limb disability and ascites was reported in POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, skin) syndrome, with an association with early death. Hematological treatment of POEMS appears effective on depression. Published literature on psychological/behavioral manifestations in inflammatory neuropathies remains scarce, and further research is needed. Muscle Nerve 54: 1-8, 2016. PMID:26999767

  12. Maladaptive immune and inflammatory pathways lead to cardiovascular insulin resistance.

    PubMed

    Aroor, Annayya R; McKarns, Susan; Demarco, Vincent G; Jia, Guanghong; Sowers, James R

    2013-11-01

    Insulin resistance is a hallmark of obesity, the cardiorenal metabolic syndrome and type 2 diabetes mellitus (T2DM). The progression of insulin resistance increases the risk for cardiovascular disease (CVD). The significance of insulin resistance is underscored by the alarming rise in the prevalence of obesity and its associated comorbidities in the Unites States and worldwide over the last 40-50 years. The incidence of obesity is also on the rise in adolescents. Furthermore, premenopausal women have lower CVD risk compared to men, but this protection is lost in the setting of obesity and insulin resistance. Although systemic and cardiovascular insulin resistance is associated with impaired insulin metabolic signaling and cardiovascular dysfunction, the mechanisms underlying insulin resistance and cardiovascular dysfunction remain poorly understood. Recent studies show that insulin resistance in obesity and diabetes is linked to a metabolic inflammatory response, a state of systemic and tissue specific chronic low grade inflammation. Evidence is also emerging that there is polarization of macrophages and lymphocytes towards a pro-inflammatory phenotype that contributes to progression of insulin resistance in obesity, cardiorenal metabolic syndrome and diabetes. In this review, we provide new insights into factors, such as, the renin-angiotensin-aldosterone system, sympathetic activation and incretin modulators (e.g., DPP-4) and immune responses that mediate this inflammatory state in obesity and other conditions characterized by insulin resistance. PMID:23932846

  13. Acute disseminated encephalomyelitis: Updates on an inflammatory CNS syndrome.

    PubMed

    Pohl, Daniela; Alper, Gulay; Van Haren, Keith; Kornberg, Andrew J; Lucchinetti, Claudia F; Tenembaum, Silvia; Belman, Anita L

    2016-08-30

    Acute disseminated encephalomyelitis (ADEM) is an immune-mediated demyelinating CNS disorder with predilection to early childhood. ADEM is generally considered a monophasic disease. However, recurrent ADEM has been described and defined as multiphasic disseminated encephalomyelitis. ADEM often occurs postinfectiously, although a causal relationship has never been established. ADEM and multiple sclerosis are currently viewed as distinct entities, generally distinguishable even at disease onset. However, pathologic studies have demonstrated transitional cases of yet unclear significance. ADEM is clinically defined by acute polyfocal neurologic deficits including encephalopathy. MRI typically demonstrates reversible, ill-defined white matter lesions of the brain and often also the spinal cord, along with frequent involvement of thalami and basal ganglia. CSF analysis may reveal a mild pleocytosis and elevated protein, but is generally negative for intrathecal oligoclonal immunoglobulin G synthesis. In the absence of a specific diagnostic test, ADEM is considered a diagnosis of exclusion, and ADEM mimics, especially those requiring a different treatment approach, have to be carefully ruled out. The role of biomarkers, including autoantibodies like anti-myelin oligodendrocyte glycoprotein, in the pathogenesis and diagnosis of ADEM is currently under debate. Based on the presumed autoimmune etiology of ADEM, the current treatment approach consists of early immunotherapy. Outcome of ADEM in pediatric patients is generally favorable, but cognitive deficits have been reported even in the absence of other neurologic sequelae. This review summarizes the current knowledge on epidemiology, pathology, clinical presentation, neuroimaging features, CSF findings, differential diagnosis, therapy, and outcome, with a focus on recent advances and controversies. PMID:27572859

  14. Renal systems biology of patients with systemic inflammatory response syndrome.

    PubMed

    Tsalik, Ephraim L; Willig, Laurel K; Rice, Brandon J; van Velkinburgh, Jennifer C; Mohney, Robert P; McDunn, Jonathan E; Dinwiddie, Darrell L; Miller, Neil A; Mayer, Eric S; Glickman, Seth W; Jaehne, Anja K; Glew, Robert H; Sopori, Mohan L; Otero, Ronny M; Harrod, Kevin S; Cairns, Charles B; Fowler, Vance G; Rivers, Emanuel P; Woods, Christopher W; Kingsmore, Stephen F; Langley, Raymond J

    2015-10-01

    A systems biology approach was used to comprehensively examine the impact of renal disease and hemodialysis (HD) on patient response during critical illness. To achieve this, we examined the metabolome, proteome, and transcriptome of 150 patients with critical illness, stratified by renal function. Quantification of plasma metabolites indicated greater change as renal function declined, with the greatest derangements in patients receiving chronic HD. Specifically, 6 uremic retention molecules, 17 other protein catabolites, 7 modified nucleosides, and 7 pentose phosphate sugars increased as renal function declined, consistent with decreased excretion or increased catabolism of amino acids and ribonucleotides. Similarly, the proteome showed increased levels of low-molecular-weight proteins and acute-phase reactants. The transcriptome revealed a broad-based decrease in mRNA levels among patients on HD. Systems integration revealed an unrecognized association between plasma RNASE1 and several RNA catabolites and modified nucleosides. Further, allantoin, N1-methyl-4-pyridone-3-carboxamide, and N-acetylaspartate were inversely correlated with the majority of significantly downregulated genes. Thus, renal function broadly affected the plasma metabolome, proteome, and peripheral blood transcriptome during critical illness; changes were not effectively mitigated by hemodialysis. These studies allude to several novel mechanisms whereby renal dysfunction contributes to critical illness.

  15. Renal systems biology of patients with systemic inflammatory response syndrome

    PubMed Central

    Tsalik, Ephraim L.; Willig, Laurel K.; Rice, Brandon J.; van Velkinburgh, Jennifer C.; Mohney, Robert P.; McDunn, Jonathan; Dinwiddie, Darrell L.; Miller, Neil A.; Mayer, Eric; Glickman, Seth W.; Jaehne, Anja K.; Glew, Robert H.; Sopori, Mohan L.; Otero, Ronny M.; Harrod, Kevin S.; Cairns, Charles B.; Fowler, Vance G.; Rivers, Emanuel P.; Woods, Christopher W.; Kingsmore, Stephen F.; Langley, Raymond J.

    2015-01-01

    A systems biology approach was used to comprehensively examine the impact of renal disease and hemodialysis (HD) on patient response during critical illness. To achieve this we examined the metabolome, proteome, and transcriptome of 150 patients with critical illness, stratified by renal function. Quantification of plasma metabolites indicated greater change as renal function declined, with the greatest derangements in patients receiving chronic HD. Specifically, 6 uremic retention molecules, 17 other protein catabolites, 7 modified nucleosides, and 7 pentose phosphate sugars increased as renal function declined, consistent with decreased excretion or increased catabolism of amino acids and ribonucleotides. Similarly, the proteome showed increased levels of low-molecular weight proteins and acute phase reactants. The transcriptome revealed a broad-based decrease in mRNA levels among patients on HD. Systems integration revealed an unrecognized association between plasma RNASE1 and several RNA catabolites and modified nucleosides. Further, allantoin, N1-methyl-4-pyridone-3-carboxamide, and n-acetylaspartate were inversely correlated with the majority of significantly down-regulated genes. Thus, renal function broadly affected the plasma metabolome, proteome, and peripheral blood transcriptome during critical illness; changes not effectively mitigated by hemodialysis. These studies allude to several novel mechanisms whereby renal dysfunction contributes to critical illness. PMID:25993322

  16. Renal systems biology of patients with systemic inflammatory response syndrome.

    PubMed

    Tsalik, Ephraim L; Willig, Laurel K; Rice, Brandon J; van Velkinburgh, Jennifer C; Mohney, Robert P; McDunn, Jonathan E; Dinwiddie, Darrell L; Miller, Neil A; Mayer, Eric S; Glickman, Seth W; Jaehne, Anja K; Glew, Robert H; Sopori, Mohan L; Otero, Ronny M; Harrod, Kevin S; Cairns, Charles B; Fowler, Vance G; Rivers, Emanuel P; Woods, Christopher W; Kingsmore, Stephen F; Langley, Raymond J

    2015-10-01

    A systems biology approach was used to comprehensively examine the impact of renal disease and hemodialysis (HD) on patient response during critical illness. To achieve this, we examined the metabolome, proteome, and transcriptome of 150 patients with critical illness, stratified by renal function. Quantification of plasma metabolites indicated greater change as renal function declined, with the greatest derangements in patients receiving chronic HD. Specifically, 6 uremic retention molecules, 17 other protein catabolites, 7 modified nucleosides, and 7 pentose phosphate sugars increased as renal function declined, consistent with decreased excretion or increased catabolism of amino acids and ribonucleotides. Similarly, the proteome showed increased levels of low-molecular-weight proteins and acute-phase reactants. The transcriptome revealed a broad-based decrease in mRNA levels among patients on HD. Systems integration revealed an unrecognized association between plasma RNASE1 and several RNA catabolites and modified nucleosides. Further, allantoin, N1-methyl-4-pyridone-3-carboxamide, and N-acetylaspartate were inversely correlated with the majority of significantly downregulated genes. Thus, renal function broadly affected the plasma metabolome, proteome, and peripheral blood transcriptome during critical illness; changes were not effectively mitigated by hemodialysis. These studies allude to several novel mechanisms whereby renal dysfunction contributes to critical illness. PMID:25993322

  17. Down Syndrome (For Kids)

    MedlinePlus

    ... Got Homework? Here's Help White House Lunch Recipes Down Syndrome KidsHealth > For Kids > Down Syndrome Print A A ... skills. continue Do a Lot of People Have Down Syndrome? Down syndrome is not contagious , so you can' ...

  18. Anesthesia & Down Syndrome

    MedlinePlus

    ... occur in individuals with Down syndrome than their peers without Down syndrome. An awareness of these more ... of the eyes, ears, and joints - just like peers without Down syndrome. What About Down Syndrome Is ...

  19. Sexuality and Down Syndrome

    MedlinePlus

    ... Down Syndrome? Down Syndrome Facts Myths & Truths Preferred Language Guide Q&A for Kids Resources New & Expectant ... Down Syndrome? Down Syndrome Facts Myths & Truths Preferred Language Guide Q&A for Kids Resources New & Expectant ...

  20. Hyperimmunoglobulin E syndrome

    MedlinePlus

    Job syndrome; Hyper IgE syndrome ... Hyperimmunoglobulin E syndrome is also called Job syndrome. It is named after the biblical character Job whose faithfulness was tested by an affliction with draining skin sores and pustules . ...

  1. Androgen insensitivity syndrome

    MedlinePlus

    ... at the tip Reifenstein syndrome (also known as Gilbert-Dreyfus syndrome or Lubs syndrome) Infertile male syndrome ... F, Leveno KJ, Bloom SL, et al., eds. Williams Obstetrics . 23rd ed. New York, NY: McGraw-Hill, ...

  2. Eicosanoids in Metabolic Syndrome

    PubMed Central

    Hardwick, James P.; Eckman, Katie; Lee, Yoon Kwang; Abdelmegeed, Mohamed A.; Esterle, Andrew; Chilian, William M.; Chiang, John Y.; Song, Byoung-Joon

    2013-01-01

    Chronic persistent inflammation plays a significant role in disease pathology of cancer, cardiovascular disease, and metabolic syndrome (MetS). MetS is a constellation of diseases that include obesity, diabetes, hypertension, dyslipidemia, hypertriglyceridemia, and hypercholesterolemia. Nonalcoholic fatty liver disease (NAFLD) is associated with many of the MetS diseases. These metabolic derangements trigger a persistent inflammatory cascade, which includes production of lipid autacoids (eicosanoids) that recruit immune cells to the site of injury and subsequent expression of cytokines and chemokines that amplify the inflammatory response. In acute inflammation, the transcellular synthesis of antiinflammatory eicosanoids resolve inflammation, while persistent activation of the autacoid-cytokine-chemokine cascade in metabolic disease leads to chronic inflammation and accompanying tissue pathology. Many drugs targeting the eicosanoid pathways have been shown to be effective in the treatment of MetS, suggesting a common linkage between inflammation, MetS and drug metabolism.The cross-talk between inflammation and MetS seems apparent because of the growing evidence linking immune cell activation and metabolic disorders such as insulin resistance, dyslipidemia, and hypertriglyceridemia. Thus modulation of lipid metabolism through either dietary adjustment or selective drugs may become a new paradigm in the treatment of metabolic disorders. This review focuses on the mechanisms linking eicosanoid metabolism to persistent inflammation and altered lipid and carbohydrate metabolism in MetS. PMID:23433458

  3. Multiple organ dysfunction syndrome.

    PubMed

    Ramírez, Michelle

    2013-01-01

    Initially known as multiple system organ failure, the term multiple organ dysfunction syndrome (MODS) was first described in the 1960s in adults with bleeding, respiratory failure, and sepsis. It is defined as "the development of potentially reversible physiologic derangement involving two or more organ systems not involved in the disorder that resulted in ICU admission, and arising in the wake of a potentially life threatening physiologic insult."(3) There are many risk factors predisposing to MODS; however, the most common risk factors are shock due to any cause, sepsis, and tissue hypoperfusion. A dysregulated immune response, or immuneparalysis, in which the homeostasis between pro-inflammatory and anti-inflammatory reaction is lost is thought to be key in the development of MODS. The clinical course and evolution of MODS is dependent on a combination of acquired and genetic factors. There are several nonspecific therapies for the prevention and resolution of MODS, mostly care is supportive. Mortality from MODS in septic pediatric patients varies between 11% and 54%.

  4. Medial tibial stress syndrome.

    PubMed

    Reshef, Noam; Guelich, David R

    2012-04-01

    MTSS is a benign, though painful, condition, and a common problem in the running athlete. It is prevalent among military personnel, runners, and dancers, showing an incidence of 4% to 35%. Common names for this problem include shin splints, soleus syndrome, tibial stress syndrome, and periostitis. The exact cause of this condition is unknown. Previous theories included an inflammatory response of the periosteum or periosteal traction reaction. More recent evidence suggests a painful stress reaction of bone. The most proven risk factors are hyperpronation of the foot, female sex, and history of previous MTSS. Patient evaluation is based on meticulous history taking and physical examination. Even though the diagnosis remains clinical, imaging studies, such as plain radiographs and bone scans are usually sufficient, although MRI is useful in borderline cases to rule out more significant pathology. Conservative treatment is almost always successful and includes several options; though none has proven more superior to rest. Prevention programs do not seem to influence the rate of MTSS, though shock-absorbing insoles have reduced MTSS rates in military personnel, and ESWT has shortened the duration of symptoms. Surgery is rarely indicated but has shown some promising results in patients who have not responded to all conservative options.

  5. Impingement syndrome in athletes.

    PubMed

    Hawkins, R J; Kennedy, J C

    1980-01-01

    Athletes, particularly those who are involved in sporting activities requiring repetitive overhead use of the arm (for example, tennis players, swimmers, baseball pitchers, and quarterbacks), may develop a painful shoulder. This is often due to impingement in the vulnerable avascular region of the supraspinatus and biceps tendons. With the passage of time, degeneration and tears of the rotator cuff may result. Pathologically the syndrome has been classified into Stage I (edema and hemorrhage), Stage II (fibrosis and tendonitis), and Stage III (tendon degeneration, bony changes, and tendon ruptures). The impingement syndrome may be a problem for the young, active, and competitive athlete as well as the casual weekend athlete. The "impingement sign" which reproduces pain and resulting facial expression when the arm is forceably forward flexed (jamming the greater tuberosity against the anteroinferior surface of the acromion) is the most reliable physical sign in establishing the diagnosis. Flexibility exercises, strengthening programs, and special training techniques are a preventive and treatment requirement. Rest and local modalities such as ice, ultrasound, and antiinflammatory agents are usually effective to lessen the inflammatory reaction. Surgical decompression by resecting the coracoacromial ligament or a more definitive anterior acromioplasty may rarely be indicated.

  6. Idiopathic inflammatory myositis.

    PubMed

    Tieu, Joanna; Lundberg, Ingrid E; Limaye, Vidya

    2016-02-01

    Knowledge on idiopathic inflammatory myopathy (IIM) has evolved with the identification of myositis-associated and myositis-specific antibodies, development of histopathological classification and the recognition of how these correlate with clinical phenotype and response to therapy. In this paper, we outline key advances in diagnosis and histopathology, including the more recent identification of antibodies associated with immune-mediated necrotising myopathy (IMNM) and inclusion body myositis (IBM). Ongoing longitudinal observational cohorts allow further classification of these patients with IIM, their predicted clinical course and response to specific therapies. Registries have been developed worldwide for this purpose. A challenging aspect in IIM, a multisystem disease with multiple clinical subtypes, has been defining disease status and clinically relevant improvement. Tools for assessing activity and damage are now recognised to be important in determining disease activity and guiding therapeutic decision-making. The International Myositis Assessment and Clinical Studies (IMACS) group has developed such tools for use in research and clinical settings. There is limited evidence for specific treatment strategies in IIM. With significant development in the understanding of IIM and improved classification, longitudinal observational cohorts and trials using validated outcome measures are necessary, to provide important information for evidence-based care in the clinical setting. PMID:27421222

  7. [Autoinflammatory syndromes: inborn errors of natural immunity].

    PubMed

    Colina, Matteo; Govoni, Marcello; De Leonardis, Francesco; Bernardi, Simone; Volpinari, Stefania; Limpido, Gessica; Trotta, Francesco

    2007-09-01

    The notion of autoinflammatory diseases delineates a heterogenous group of genetic pathologies characterized by spontaneous periodic systemic inflammation in the absence of infectious or autoimmune causes. The general hypothesis is that the innate immune response in these patients is wrongly tuned, being either too sensitive to minor stimuli or turned off too late. Clinical pictures of these disorders are characterized by high spiking fever associated with involvement of musculo-skeletal system, tegumentary apparatus and serosas. Although inflammatory syndromes are considered rare, they may represent a model in order to unravel some aspects of the innate immune system and of the inflammatory cascade.

  8. [Sudeck's syndrome. Was Sudeck right?].

    PubMed

    van der Laan, L; Goris, R J

    1997-02-01

    Reflex sympathetic dystrophy (RSD) is a syndrome affecting an extremity after a minor trauma or operation. At the moment there is no consensus about the pathogenesis of RSD. In 1942 Paul Sudeck suggested that the signs and symptoms of RSD may be provoked by an exaggerated inflammatory response to injury or operation of an extremity. His theory found no disciples, as most physicians believe that RSD is initiated by an hyperactive sympathetic system. We performed various clinical and experimental investigations, including the effects of antiinflammatory treatment. The results of these studies support the theory of Paul Sudeck. PMID:9157569

  9. Inflammatory networks underlying colorectal cancer.

    PubMed

    Lasry, Audrey; Zinger, Adar; Ben-Neriah, Yinon

    2016-03-01

    Inflammation is emerging as one of the hallmarks of cancer, yet its role in most tumors remains unclear. Whereas a minority of solid tumors are associated with overt inflammation, long-term treatment with non-steroidal anti-inflammatory drugs is remarkably effective in reducing cancer rate and death. This indicates that inflammation might have many as-yet-unrecognized facets, among which an indolent course might be far more prevalent than previously appreciated. In this Review, we explore the various inflammatory processes underlying the development and progression of colorectal cancer and discuss anti-inflammatory means for its prevention and treatment.

  10. Pyogenic Arthritis, Pyoderma Gangrenosum, Acne, Suppurative Hidradenitis (PA-PASH) Syndrome: An Atypical Presentation of a Rare Syndrome

    PubMed Central

    Ursani, Mohammad A.; Appleyard, Joan; Whiteru, Onome

    2016-01-01

    Patient: Male, 44 Final Diagnosis: PAPASH syndrome Symptoms: Recurrent skin ulcers • diarrhea • inflammatory arthritis Medication: Prednisone • anti-tumor necrosis factor Clinical Procedure: N/A Specialty: Rheumatology Objective: Rare disease Background: Pyogenic arthritis, pyoderma gangrenosum (PG), acne, and suppurative hidradenitis (PA-PASH) syndrome has been linked to an auto-inflammatory pathway. We report a case that is an atypical presentation of a rare syndrome, which supports literature suggesting that different phenotypes of PG-related syndromes may be a variation of the same pathogenic spectrum. Interestingly, our patient displayed a positive proteinase-3 antibody (PR-3). The clinical relevance of this is unclear. In recent literature, antineutrophil cytoplasmic autoantibodies (ANCA) positivity has been reported in various inflammatory conditions other than ANCA-associated vasculitis (AAV). Case Report: A 44-year-old African American male with history of pyogenic arthritis, acne, suppurative hidradenitis, and chronic diarrhea presented for evaluation of painful ulcers located on the bilateral lower extremities, bilateral proximal interphalangeal joints, buttocks, and scrotum, and chronic diarrhea. Infectious etiologies for the ulcers were ruled out. Biopsy of an ulcer revealed PG. Colonoscopy revealed inflammation and ulceration with biopsy consistent with ulcerative colitis (UC). After treatment with prednisone, the ulcers healed within 4 weeks, and the chronic diarrhea resolved. Conclusions: Our patient displayed a variation of PA-PASH syndrome and UC. Previously reported cases of similar phenotypes of PG-related syndromes have not presented in this fashion. Furthermore, the literature does not report cases of PG-related syndromes with an elevation in PR-3 antibody. Elevation in PR-3 has been reported in various inflammatory disorders aside from AAV. The relevance of this is currently unclear. It may be possible that the milieus of these various

  11. Chlamydial pelvic inflammatory disease.

    PubMed

    Paavonen, J; Lehtinen, M

    1996-01-01

    Pelvic inflammatory disease (PID) is the most important complication present in the female lower genital tract, causing major medical, social and economic problems. Although PID can be caused by multiple microorganisms, it results most frequently from the ascent of sexually transmitted Chlamydia.trachomatis or Neisseria gonorrhoeae infections from the cervix to the upper genital tract. The importance of cervical chlamydial infection in the pathogenesis of PID is well recognized. Recent data from many developed countries have shown a striking decrease in the incidence of gonococcal infections, while the rates of chlamydial infections remain high in most countries. Complications of PID are common and usually irreversible. Emerging evidence suggests that universal or selected screening of defined populations for cervical chlamydial infection leads to a dramatic reduction in the incidence of PID. Recent technological advances should further enhance efforts to prevent chlamydial infection and PID. Gene amplification-based diagnostic tests, screening by testing first-void urine, and single dose antimicrobial therapy greatly facilitate chlamydia control programmes. Thus, screening for chlamydia is the key approach in the secondary prevention of PID. The obvious challenge is to make screening for chlamydia the standard for health care for young, sexually active individuals. Since PID is the most important consequence of sexually transmitted bacterial infections, it is also imperative to develop better treatments to prevent the long-term sequelae of this disease. The development and implementation of new and effective intervention programmes for prevention and control of PID is one of the major challenges for the year 2000 and beyond. PMID:9111185

  12. Facilitated spinal neuropeptide signaling and upregulated inflammatory mediator expression contribute to postfracture nociceptive sensitization.

    PubMed

    Shi, Xiaoyou; Guo, Tian-Zhi; Wei, Tzuping; Li, Wen-Wu; Clark, David J; Kingery, Wade S

    2015-10-01

    Tibia fracture induces exaggerated substance P (SP) and calcitonin gene-related peptide (CGRP) signaling and neuropeptide-dependent nociceptive and inflammatory changes in the hind limbs of rats similar to those seen in complex regional pain syndrome. Inflammatory changes in the spinal cord contribute to nociceptive sensitization in a variety of animal pain models. This study tested the hypothesis that fracture-induced exaggerated neuropeptide signaling upregulates spinal inflammatory mediator expression, leading to postfracture hind limb nociceptive sensitization. At 4 weeks after performing tibia fracture and casting in rats, we measured hind limb allodynia, unweighting, warmth, edema, and spinal cord neuropeptide and inflammatory mediator content. The antinociceptive effects of intrathecally injected neuropeptide and inflammatory mediator receptor antagonists were evaluated in fracture rats. Transgenic fracture mice lacking SP or the CGRP RAMP1 receptor were used to determine the effects of neuropeptide signaling on postfracture pain behavior and spinal inflammatory mediator expression. Hind limb allodynia, unweighting, warmth, edema, increased spinal SP and CGRP, and increased spinal inflammatory mediator expression (TNF, IL-1, IL-6, CCL2, and nerve growth factor) were observed at 4 weeks after fracture in rats. Fracture-induced increases in spinal inflammatory mediators were not observed in fracture mice lacking SP or the CGRP receptor, and these mice had attenuated postfracture nociceptive sensitization. Intrathecal injection of selective receptor antagonists for SP, CGRP, TNF, IL-1, IL-6, CCL2, or nerve growth factor each reduced pain behaviors in the fracture rats. Collectively, these data support the hypothesis that facilitated spinal neuropeptide signaling upregulates the expression of spinal inflammatory mediators contributing to nociceptive sensitization in a rodent fracture model of complex regional pain syndrome. PMID:25932690

  13. Facilitated spinal neuropeptide signaling and upregulated inflammatory mediator expression contribute to postfracture nociceptive sensitization.

    PubMed

    Shi, Xiaoyou; Guo, Tian-Zhi; Wei, Tzuping; Li, Wen-Wu; Clark, David J; Kingery, Wade S

    2015-10-01

    Tibia fracture induces exaggerated substance P (SP) and calcitonin gene-related peptide (CGRP) signaling and neuropeptide-dependent nociceptive and inflammatory changes in the hind limbs of rats similar to those seen in complex regional pain syndrome. Inflammatory changes in the spinal cord contribute to nociceptive sensitization in a variety of animal pain models. This study tested the hypothesis that fracture-induced exaggerated neuropeptide signaling upregulates spinal inflammatory mediator expression, leading to postfracture hind limb nociceptive sensitization. At 4 weeks after performing tibia fracture and casting in rats, we measured hind limb allodynia, unweighting, warmth, edema, and spinal cord neuropeptide and inflammatory mediator content. The antinociceptive effects of intrathecally injected neuropeptide and inflammatory mediator receptor antagonists were evaluated in fracture rats. Transgenic fracture mice lacking SP or the CGRP RAMP1 receptor were used to determine the effects of neuropeptide signaling on postfracture pain behavior and spinal inflammatory mediator expression. Hind limb allodynia, unweighting, warmth, edema, increased spinal SP and CGRP, and increased spinal inflammatory mediator expression (TNF, IL-1, IL-6, CCL2, and nerve growth factor) were observed at 4 weeks after fracture in rats. Fracture-induced increases in spinal inflammatory mediators were not observed in fracture mice lacking SP or the CGRP receptor, and these mice had attenuated postfracture nociceptive sensitization. Intrathecal injection of selective receptor antagonists for SP, CGRP, TNF, IL-1, IL-6, CCL2, or nerve growth factor each reduced pain behaviors in the fracture rats. Collectively, these data support the hypothesis that facilitated spinal neuropeptide signaling upregulates the expression of spinal inflammatory mediators contributing to nociceptive sensitization in a rodent fracture model of complex regional pain syndrome.

  14. Accelerated atherosclerosis in patients with chronic inflammatory rheumatologic conditions

    PubMed Central

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

    2015-01-01

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

  15. Lymphogranuloma venereum proctosigmoiditis is a mimicker of inflammatory bowel disease

    PubMed Central

    Gallegos, Marlene; Bradly, Dawn; Jakate, Shriram; Keshavarzian, Ali

    2012-01-01

    There has been an increasing prevalence of lymphogranuloma venereum (LGV) or Chlamydia trachomatis (C. trachomatis) cases among the men who have sex with men (MSM) population, particularly in Europe and North America. These cases may present with an incomplete or undisclosed history and proctosigmoiditis without characteristic adenopathy syndrome. During the initial evaluation and colonoscopy, there is a strong clinical and endoscopic suspicion of inflammatory bowel disease (IBD) by virtue of presentation and endoscopic and histological findings. The diagnosis of IBD is subsequently modified to LGV proctosigmoiditis when one or more of the following transpire: (1) there is failure of response to IBD therapy; (2) additional components of history (MSM/travel) may be identified; (3) return of initially performed Chlamydia antibody test is positive; and (4) response to antibiotics effective against Chlamydia. We describe three such cases initially suspected to be an inflammatory bowel disease and subsequently identified as C. trachomatis proctosigmoiditis. PMID:22783058

  16. Lymphogranuloma venereum proctosigmoiditis is a mimicker of inflammatory bowel disease.

    PubMed

    Gallegos, Marlene; Bradly, Dawn; Jakate, Shriram; Keshavarzian, Ali

    2012-07-01

    There has been an increasing prevalence of lymphogranuloma venereum (LGV) or Chlamydia trachomatis (C. trachomatis) cases among the men who have sex with men (MSM) population, particularly in Europe and North America. These cases may present with an incomplete or undisclosed history and proctosigmoiditis without characteristic adenopathy syndrome. During the initial evaluation and colonoscopy, there is a strong clinical and endoscopic suspicion of inflammatory bowel disease (IBD) by virtue of presentation and endoscopic and histological findings. The diagnosis of IBD is subsequently modified to LGV proctosigmoiditis when one or more of the following transpire: (1) there is failure of response to IBD therapy; (2) additional components of history (MSM/travel) may be identified; (3) return of initially performed Chlamydia antibody test is positive; and (4) response to antibiotics effective against Chlamydia. We describe three such cases initially suspected to be an inflammatory bowel disease and subsequently identified as C. trachomatis proctosigmoiditis. PMID:22783058

  17. Develop Anti-Inflammatory Nanotherapies to Treat Cardiovascular Disease

    NASA Astrophysics Data System (ADS)

    Tang, Jun

    Cardiovascular disease (CVD) is the leading cause of disease-related death in the world, accounting for 30 % global mortality. The majority of CVD is caused by atherosclerosis, a chronic inflammatory disease of major arteries featured by the deposition of lipids and cholesterol. Inflammation of atherosclerosis is mainly promoted by the pathological macrophages and monocytes, and modulating their functions has been proposed as a promising therapeutic target. This dissertation first presents the development of a novel simvastatin-loaded high-density lipoprotein (HDL) based nanoparticle ([S]-rHDL), which was able to deliver anti-inflammatory simvastatin preferentially to inflammatory monocytes in the blood and to macrophages in advanced atherosclerotic plaques, leading to the reduced inflammation in the tissue. Second, extensive in vivo characterization of [S]-rHDL in a mouse atherosclerosis model revealed that the anti-inflammatory capability of [S]-rHDL derived from its effects on blood monocytes, endothelial layer, monocyte recruitment, and plaque macrophage function. Third, a translational study that integrated the use of [S]-rHDL into oral statin treatment demonstrated a great potential for this nanomedicine as an attractive addition to the current high-dose oral statin standard-of-care for acute coronary syndrome. Finally, preliminary results suggested potential applications of the rHDL platform to other macrophage-implicated diseases.

  18. [Vulvar lichen sclerosus in a girl with Turner syndrome].

    PubMed

    Ocampo, Dolores; González, Verónica

    2014-08-01

    Dermatological complications in Turner syndrome are infrequent but occasionally cause significant morbidity. Lichen sclerosus (LS) is a chronic inflammatory mucocutaneous affection characterized by pruritus in the anogenital area. It is yet not clear its pathophysiology but it's linked with genetic factors and autoimmunity. This is a case report of a girl with Turner syndrome with growth hormone treatment that started with vulvar pruritus and was diagnosed as lichen sclerosus. PMID:24955917

  19. [Sneddon's syndrome: 4 cases and a review of the literature].

    PubMed

    Abouzahir, A; Bourazza, A; Rafik, R; Karouach, K; Boutaleb, N; Ouhabi, H; Mosseddaq, R; Ohayon, V; Archane, M-I

    2003-12-01

    Sneddon syndrome is an association of livedo racemosa and cerebrovascular ischemic events generally occurring in young adults. This is an uncommon chronic progressive arterio-occlusive disorder of unknown cause involving small and medium sized vessels. We report four cases. One case was disclosed by cerebral hemorrhage. One pathogenic hypothesis suggests the involvement of an idiopathic progressive inflammatory arteriopathy or secondary thrombotic disorder comparable with antiphospholipid syndrome.

  20. Microcephaly syndromes.

    PubMed

    Abuelo, Dianne

    2007-09-01

    The objective of this article is to review microcephaly from a genetics point of view, especially with regard to the process of identification of syndromes in which small head circumference occurs. Microcephaly can be due to either genetic or environmental causes. It can be the only positive finding or may be part of a syndrome of congenital anomalies. The genetic etiology can be caused by autosomal dominant, autosomal recessive, or X-linked genes or various types of chromosome anomalies. Some of the gene mutations have been identified recently. Syndromic microcephaly is associated with a large number of conditions. Some can be diagnosed, or at least suspected, based on their characteristic facial dysmorphism, and others can be searched for using databases of genetic disorders.

  1. Premenstrual syndrome.

    PubMed

    Parker, P D

    1994-11-01

    Premenstrual syndrome is characterized by an array of somatic, cognitive, affective and behavioral disturbances that recur in cyclic fashion during the luteal phase of the menstrual cycle. The goal of management is to control symptoms well enough that the patient can function appropriately at all stages of the menstrual cycle. Both the patient and the physician must acknowledge that premenstrual syndrome is a complex reproductive disorder with a large number of possible manifestations; therefore, they must be willing to consider more than one strategy, and they must allow sufficient time to seek out successful therapeutic options. The patient must play an active role in all stages of management. Although no specific cure for premenstrual syndrome currently exists, most patients experience significant reduction of symptoms and improvement of quality of life when a rational individualized approach is used. Management may involve pharmacologic, nutritional and psychosocial interventions. PMID:7942429

  2. Compartment syndromes

    NASA Technical Reports Server (NTRS)

    Mubarak, S. J.; Pedowitz, R. A.; Hargens, A. R.

    1989-01-01

    The compartment syndrome is defined as a condition in which high pressure within a closed fascial space (muscle compartment) reduces capillary blood perfusion below the level necessary for tissue viability'. This condition occurs in acute and chronic (exertional) forms, and may be secondary to a variety of causes. The end-result of an extended period of elevated intramuscular pressure may be the development of irreversible tissue injury and Volkmann's contracture. The goal of treatment of the compartment syndrome is the reduction of intracompartmental pressure thus facilitating reperfusion of ischaemic tissue and this goal may be achieved by decompressive fasciotomy. Controversy exists regarding the critical pressure-time thresholds for surgical decompression and the optimal diagnostic methods of measuring intracompartmental pressures. This paper will update and review some current knowledge regarding the pathophysiology, aetiology, diagnosis, and treatment of the acute compartment syndrome.

  3. Refeeding syndrome.

    PubMed

    Tripathy, Swagata; Mishra, Padmini; Dash, S C

    2008-07-01

    We report a case of a fifty-year-old male who was admitted with a three month history of increasing weakness, prostration, decreasing appetite and inability to swallow. The patient was a chronic alcoholic, unemployed, and of very poor socioeconomic background. The patient was initially investigated for upper GI malignancy, Addisons disease, bulbar palsy and other endocrinopathies. Concurrent management was started for severe electrolyte abnormalities and enteral nutritional supplementation was begun. By the fourth day of feeding patient developed severe hypophosphatemia and other life-threatening features suggesting refeeding syndrome. The patient was managed for the manifestations of refeeding syndrome. A final diagnosis of chronic alcoholic malnutrition with refeeding syndrome was made. Refeeding of previously starving patients may lead to a variety of complications including sudden death.

  4. Controversies involving hypercapnic acidosis in acute respiratory distress syndrome.

    PubMed

    Nardelli, Liliane; Rocco, Patricia Rieken Macedo; Garcia, Cristiane Sousa Nascimento Baez

    2009-12-01

    Acute respiratory distress syndrome is characterized by a diffuse inflammatory reaction of lung parenchyma induced by a direct insult to the alveolar epithelium (pulmonary acute respiratory distress syndrome) or an indirect lesion through the vascular endothelium (extrapulmonary acute respiratory distress syndrome). The main therapeutic strategy for acute respiratory distress syndrome is the ventilatory support. However, mechanical ventilation can worsen lung injury. In this context, a protective ventilatory strategy with low tidal volume has been proposed. The use of low tidal volume reduced the mortality rate of acute respiratory distress syndrome patients, but result in hypercapnic acidosis. The current article presents a review of literature on the effects of permissive hypercapnia in acute respiratory distress syndrome. To that end, we carried out a systematic review of scientific literature based on established criteria for documental analysis including clinical and experimental articles, using as data bases MedLine, LILACS, SciELO, PubMed, Cochrane. Hypercapnic acidosis has been considered by some authors as a modulator of the inflammatory process of acute respiratory distress syndrome. However, clinical and experimental studies on the effects of hypercapnic acidosis have shown controversial results. Therefore it is important to better elucidate the role of hypercapnic acidosis in acute respiratory distress syndrome.

  5. [Autoinflammatory disorders: a new concept in hereditary periodic fever syndromes].

    PubMed

    Horcada Rubio, M L; Delgado Beltrán, C; Armas Ramírez, C

    2004-03-01

    At last year the great scientific advances in genetics and molecular biology have led to a bigger knowledge about we nowadays call "Autoinflammatory syndromes", characterized by recurrent inflammatory episodes genetically determined and not mediated by autoimmunity. In this group, they are included the hereditary periodic fever syndromes: familial mediterranean fever (FMF), hyper Ig-D syndrome (HIDS), TNF-receptor-associated periodic syndrome (TRAPS), Muckle-Wells syndrome (MWS), familial cold autoinflammatory syndrome (FCAS), CINCA syndrome. The past 6 year have witnessed the identification of genes causing these diseases. Some of these genes encode proteins with a common domain (PYRIN domain). These protein are part of regulatory pathway of inflammation and apoptosis. The purpose of this article, is to carry out review of the genetic, clinical, molecular and rheumatologic aspect of these syndromes, in part unknown. Although they are not common, they are not absent in our diary clinical practise. Their study and research we will be able to obtain new knowledge that lead us to solve the complex inflammatory process. PMID:15043497

  6. Complications of inflammatory bowel disease.

    PubMed

    Gasche, C

    2000-01-01

    Complications in inflammatory bowel disease determine the severity of disease as well as the complexities of medical or surgical treatment opportunities. Therefore, in known inflammatory bowel disease, the prevention, the early detection and the adequate therapeutic response to certain complications are important goals in the follow-up of inflammatory bowel disease patients. Disease complications are separated into intestinal and extraintestinal complications. Intestinal complications are somewhat disease specific, which means that they occur exclusively in either Crohn's disease or ulcerative colitis (e.g., enteric fistulas are particularly found in Crohn's disease and toxic megacolon in ulcerative colitis). Most extraintestinal complications occur in both forms of inflammatory bowel disease (e.g., anemia, thromboembolic events or osteoporosis). The current knowledge on pathogenesis, diagnostic tools, prevention and treatment of certain intestinal and extraintestinal complications is reviewed. PMID:10690585

  7. Macrophage polarization in inflammatory diseases.

    PubMed

    Liu, Yan-Cun; Zou, Xian-Biao; Chai, Yan-Fen; Yao, Yong-Ming

    2014-01-01

    Diversity and plasticity are two hallmarks of macrophages. M1 macrophages (classically activated macrophages) are pro-inflammatory and have a central role in host defense against infection, while M2 macrophages (alternatively activated macrophages) are associated with responses to anti-inflammatory reactions and tissue remodeling, and they represent two terminals of the full spectrum of macrophage activation. Transformation of different phenotypes of macrophages regulates the initiation, development, and cessation of inflammatory diseases. Here we reviewed the characters and functions of macrophage polarization in infection, atherosclerosis, obesity, tumor, asthma, and sepsis, and proposed that targeting macrophage polarization and skewing their phenotype to adapt to the microenvironment might hold great promise for the treatment of inflammatory diseases.

  8. Update on idiopathic inflammatory myopathies.

    PubMed

    Briani, C; Doria, A; Sarzi-Puttini, P; Dalakas, M C

    2006-05-01

    The inflammatory myopathies are a group of acquired diseases, characterized by an inflammatory infiltrate of the skeletal muscle. On the basis of clinical, immuno-pathological and demographic features, three major diseases can be identified: dermatomyositis (DM); polymyositis (PM); and inclusion body myositis (IBM). New diagnostic criteria have recently been introduced, which are crucial for discriminating between the three different subsets of inflammatory myopathies and for excluding other disorders. DM is a complement-mediated microangiopathy affecting skin and muscle. PM and IBM are T cell-mediated disorders, where CD8-positive cytotoxic T cells invade muscle fibres expressing MHC class I antigens, thus leading to fibre necrosis. In IBM, vacuolar formation with amyloid deposits are also present. This article summarizes the main clinical, laboratory, electrophysiological, immunological and histologic features as well as the therapeutic options of the inflammatory myopathies.

  9. Inflammatory bowel disease, liver diseases and endothelial function: is there a linkage?

    PubMed

    Ciccone, Marco Matteo; Principi, Mariabeatrice; Ierardi, Enzo; Di Leo, Alfredo; Ricci, Gabriella; Carbonara, Santa; Gesualdo, Michele; Devito, Fiorella; Zito, Annapaola; Cortese, Francesca; Scicchitano, Pietro

    2015-01-01

    Atherosclerosis is a systemic inflammatory disease able to deeply worsen the outcome of patients because of its serious clinical consequences. The complex inflammatory background underlining such a disease makes atherosclerosis linked to several systemic inflammatory conditions able to impair endothelial function and morphology. Inflammatory bowel diseases are a group of gastrointestinal diseases including Crohn's disease and ulcerative colitis, that is, syndromes characterized by changes in mucosal immunity and gastrointestinal physiology, which could negatively influence the vascular endothelial function and structure. Hepatitis (i.e. inflammatory diseases of the liver mainly due to viral infections) and nonalcoholic fatty liver disease could be aligned to inflammatory bowel disease in such an induction of atherosclerosis disease.Many studies tried to point out the relationship between bowel and liver inflammatory diseases and early vascular changes, considered the first step for atherosclerosis development.The aim of such a narrative review is to explain the relationship between inflammatory bowel disease, hepatitis and nonalcoholic fatty liver disease and their role in increasing cardiovascular risk profile due to early impairment in vascular function and morphology.

  10. Flammer syndrome

    PubMed Central

    2014-01-01

    The new term Flammer syndrome describes a phenotype characterized by the presence of primary vascular dysregulation together with a cluster of symptoms and signs that may occur in healthy people as well as people with disease. Typically, the blood vessels of the subjects with Flammer syndrome react differently to a number of stimuli, such as cold and physical or emotional stress. Nearly all organs, particularly the eye, can be involved. Although the syndrome has some advantages, such as protection against the development of atherosclerosis, Flammer syndrome also contributes to certain diseases, such as normal tension glaucoma. The syndrome occurs more often in women than in men, in slender people than in obese subjects, in people with indoor rather than outdoor jobs, and in academics than in blue collar workers. Affected subjects tend to have cold extremities, low blood pressure, prolonged sleep onset time, shifted circadian rhythm, reduced feeling of thirst, altered drug sensitivity, and increased general sensitivity, including pain sensitivity. The plasma level of endothelin-1 is slightly increased, and the gene expression in lymphocytes is changed. In the eye, the retinal vessels are stiffer and their spatial variability larger; the autoregulation of ocular blood flow is decreased. Glaucoma patients with Flammer syndrome have an increased frequency of the following: optic disc hemorrhages, activated retinal astrocytes, elevated retinal venous pressure, optic nerve compartmentalization, fluctuating diffuse visual field defects, and elevated oxidative stress. Further research should lead to a more concise definition, a precise diagnosis, and tools for recognizing people at risk. This may ultimately lead to more efficient and more personalized treatment. PMID:25075228

  11. Novel Inflammatory Biomarkers in Coronary Artery Disease: Potential Therapeutic Approaches.

    PubMed

    Voudris, Konstantinos V; Chanin, Jake; Feldman, Dmitriy N; Charitakis, Konstantinos

    2015-01-01

    Coronary artery disease constitutes the leading cause of mortality and morbidity in the modern world. Inflammation has been implicated to play a key role in the initiation and promotion of atherosclerosis, and the induction of plaque instability, possibly leading to acute coronary syndrome (ACS). This review aims to assess the clinical utility of well established (CRP) and novel inflammatory biomarkers (Homocyesteine, SAA, sCD40L, sLOX-1, IMA, MPO, PAPP-A and MMPs) in the diagnosis and outcome prediction of patients with ACS. The PubMed database was searched for reports using the terms "biomarkers", "acute coronary syndrome", "infarction", "markers" and only original articles written in English were included. The diversity of novel biomarkers for coronary artery disease provides an insight of the varied pathophysiology of this disease. A better understanding of their properties and assimilation in daily clinical use is essential for optimal management and patient care in the future. PMID:25891107

  12. The Vogt-Koyanagi-Harada syndrome: association with hypothyroidism and diabetes mellitus.

    PubMed Central

    Jaggarao, N.; Voth, D.; Jacobsen, J.

    1989-01-01

    A 45 year old Saudi male with poliosis, alopecia areata, vitiligo, anterior uveitis, inflammatory changes in the posterior pole of the retina and paraparesis presented with features of the Vogt-Koyanagi-Harada syndrome, uncontrolled diabetes mellitus and hypothyroidism. To the best of our knowledge the association of diabetes mellitus and hypothyroidism in this syndrome has not been reported previously. PMID:2602259

  13. Molecular cues guiding inflammatory responses.

    PubMed

    Barreiro, Olga; Martín, Pilar; González-Amaro, Roberto; Sánchez-Madrid, Francisco

    2010-05-01

    Alarm signals generated at inflammatory foci reach the vascular lumen to attract immune cells towards the affected tissue. Different leucocyte subsets decipher and integrate these complex signals in order to make adequate decisions for their migration towards the inflamed tissue. Soluble cues (cytokines and chemokines) and membrane receptors in both endothelium and leucocytes orchestrate the coordinated recruitment of specific inflammatory cell subsets. All these molecules are spatio-temporally organized in specialized structures at the luminal side of endothelium and the leucocyte membrane or are generated as chemical gradients in the damaged tissue. Thus, the repertoire of chemokines and their receptors as well as adhesion molecules expressed by each leucocyte subset determine their recruitment for participation in specific inflammatory pathologies. Whenever inflammatory signals are altered or misprocessed, inflammation can become chronic, causing extensive tissue damage. To combat chronic inflammation and autoimmune diseases, novel therapeutic strategies attempt to silence the predominant signals in each inflammatory scenario. In this review, we provide a general overview of all these aspects related to the molecular regulation of leucocyte guidance in inflammatory responses.

  14. Myositis in Griscelli syndrome type 2 treated with hematopoietic cell transplantation.

    PubMed

    Born, Alfred Peter; Müller, Klaus; Marquart, Hanne Vibeke; Heilmann, Carsten; Schejbel, Lone; Vissing, John

    2010-02-01

    Griscelli syndrome is an autosomal recessive disorder characterized by pigmentary dilution and is occasionally associated with a hemophagocytic syndrome (type 2). We present a 13-year-old girl with Griscelli syndrome type 2, who developed a hemophagocytic syndrome along with marked muscle weakness and elevated plasma creatine kinase. Muscle biopsy showed massive inflammatory changes in some fascicles, while other fascicles were relatively spared. Clinical symptoms and biopsy changes resolved after immunosuppression and allogeneic hematopoietic cell transplantation. Our results suggest that muscle involvement should be considered in patients with hemophagocytic syndrome to ensure proper treatment.

  15. Neurologic complications of systemic lupus erythematosus, sjögren syndrome, and rheumatoid arthritis.

    PubMed

    Bhattacharyya, Shamik; Helfgott, Simon M

    2014-09-01

    Neurologic complications are frequent and often morbid in systemic lupus erythematosus, Sjögren syndrome, and rheumatoid arthritis. Although all are systemic inflammatory syndromes, each disease affects the nervous system distinctly, such as peripheral neuropathy in Sjögren syndrome, cerebrovascular disease in lupus, and cervical spine subluxation in rheumatoid arthritis. Some neurologic complications share convergent pathophysiology across diseases, such as neuromyelitis optica spectrum disorders in both Sjögren syndrome and lupus. Ill-defined cognitive complaints are especially common in lupus and Sjögren syndrome. For the majority of the complications, evidence for treatment efficacy is limited and requires further investigation.

  16. Antisynthetase Syndrome: A Rare Cause for ILD

    PubMed Central

    Pasha, MD Majeed; Padmaja, Mantha Sathya; Halappa, Sujith

    2016-01-01

    Anti-Synthetase Syndrome (ASS) is a rare autoimmune disorder characterized by Interstitial Lung Disease (ILD), inflammatory myositis, fever, Raynaud’s phenomenon, mechanic’s hand, and inflammatory polyarthritis in the setting of antibodies against amino acyl-transfer RNA synthetases, with anti-Jo-1 antibody being the most common. It can sometimes present as interstitial lung disease without any other expression of the syndrome. Clinical and radiological features can be similar to atypical pneumonia and could be a challenge to diagnose at an early stage. Prognosis is generally poor, especially when there is associated ILD and delay in diagnosis can lead to increase in morbidity due to progression of pulmonary involvement. We report a patient of ASS presenting with ILD, diagnosed early and treated successfully with immunosupression. PMID:27134916

  17. Antisynthetase Syndrome: A Rare Cause for ILD.

    PubMed

    Devi, Hj Gayathri; Pasha, Md Majeed; Padmaja, Mantha Sathya; Halappa, Sujith

    2016-03-01

    Anti-Synthetase Syndrome (ASS) is a rare autoimmune disorder characterized by Interstitial Lung Disease (ILD), inflammatory myositis, fever, Raynaud's phenomenon, mechanic's hand, and inflammatory polyarthritis in the setting of antibodies against amino acyl-transfer RNA synthetases, with anti-Jo-1 antibody being the most common. It can sometimes present as interstitial lung disease without any other expression of the syndrome. Clinical and radiological features can be similar to atypical pneumonia and could be a challenge to diagnose at an early stage. Prognosis is generally poor, especially when there is associated ILD and delay in diagnosis can lead to increase in morbidity due to progression of pulmonary involvement. We report a patient of ASS presenting with ILD, diagnosed early and treated successfully with immunosupression. PMID:27134916

  18. Immunopathogenesis of inflammatory myopathies.

    PubMed

    Dalakas, M C

    1995-05-01

    Immune-mediated mechanisms appear to play a primary role in the pathogenesis of polymyositis (PM) and dermatomyositis (DM). The serum of patients with active DM has high levels of circulating complement fragments C3b, C4b, and C5b-9 membranolytic attack complex (MAC) and demonstrates a very high C3 uptake in an vitro assay system. The MAC and the immune complex-specific C3bNEO fragment are deposited on the endomysial capillaries early in the disease and lead sequentially to loss of capillaries, muscle ischemia, muscle fiber necrosis, and perifascicular atrophy. In contrast, in PM the muscle fiber injury is initiated by sensitized CD8+ cytotoxic T cells that recognize heretofore unknown and probably endogenous muscle antigens in the context of major histocompatibility complex (MHC) class I expression. A restricted (oligoclonal) pattern of T-cell receptor with prominence of Va1, Vb6, and Vb15 genes is noted within the endomysial infiltrates suggesting that the T-cell response is antigen driven. In both PM and DM, intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 are upregulated in the endomysial endothelial cells and function as ligands for the leukocyte integrins leukocyte function-associated antigen (LFA)-1 and very late activating antigen (VLA)-4, allowing activated lymphocytes to adhere to the endothelial cells and migrate to the muscle fibers. Among viruses, only the retroviruses human immunodeficiency virus (HIV) and human T-cell lymphotropic virus (HTLV)-1 have been convincingly shown to trigger PM, which is mediated by nonviral-specific, cytotoxic CD8+ cells. The treatment of inflammatory myopathies remains empirical. Many patients respond to steroids to some degree and for some period of time. Azathioprine, methotrexate, cyclosporine, cyclophosphamide, and plasmapheresis can be of mild to moderate benefit. High-dose intravenous immunoglobulin (IVIg) is a promising therapeutic modality for some patients resistant to

  19. Inflammatory bowel disease: the role of inflammatory cytokine gene polymorphisms.

    PubMed Central

    Balding, Joanna; Livingstone, Wendy J; Conroy, Judith; Mynett-Johnson, Lesley; Weir, Donald G; Mahmud, Nasir; Smith, Owen P

    2004-01-01

    The mechanisms responsible for development of inflammatory bowel disease (IBD) have not been fully elucidated, although the main cause of disease pathology is attributed to up-regulated inflammatory processes. The aim of this study was to investigate frequencies of polymorphisms in genes encoding pro-inflammatory and anti-inflammatory markers in IBD patients and controls. We determined genotypes of patients with IBD (n= 172) and healthy controls (n= 389) for polymorphisms in genes encoding various cytokines (interleukin (IL)-1beta, IL-6, tumour necrosis factor (TNF), IL-10, IL-1 receptor antagonist). Association of these genotypes to disease incidence and pathophysiology was investigated. No strong association was found with occurrence of IBD. Variation was observed between the ulcerative colitis study group and the control population for the TNF-alpha-308 polymorphism (p= 0.0135). There was also variation in the frequency of IL-6-174 and TNF-alpha-308 genotypes in the ulcerative colitis group compared with the Crohn's disease group (p= 0.01). We concluded that polymorphisms in inflammatory genes are associated with variations in IBD phenotype and disease susceptibility. Whether the polymorphisms are directly involved in regulating cytokine production, and consequently pathophysiology of IBD, or serve merely as markers in linkage disequilibrium with susceptibility genes remains unclear. PMID:15223609

  20. Inflammatory mechanisms in ischemic stroke: role of inflammatory cells

    PubMed Central

    Jin, Rong; Yang, Guojun; Li, Guohong

    2010-01-01

    Inflammation plays an important role in the pathogenesis of ischemic stroke and other forms of ischemic brain injury. Experimentally and clinically, the brain responds to ischemic injury with an acute and prolonged inflammatory process, characterized by rapid activation of resident cells (mainly microglia), production of proinflammatory mediators, and infiltration of various types of inflammatory cells (including neutrophils, different subtypes of T cells, monocyte/macrophages, and other cells) into the ischemic brain tissue. These cellular events collaboratively contribute to ischemic brain injury. Despite intense investigation, there are still numerous controversies concerning the time course of the recruitment of inflammatory cells in the brain and their pathogenic roles in ischemic brain injury. In this review, we provide an overview of the time-dependent recruitment of different inflammatory cells following focal cerebral I/R. We discuss how these cells contribute to ischemic brain injury and highlight certain recent findings and currently unanswered questions about inflammatory cells in the pathophysiology of ischemic stroke. PMID:20130219

  1. Tourette Syndrome

    MedlinePlus

    ... is also possible that many genes with smaller effects and environmental factors may play a role in the development ... Publication No. 12-2163 Back to Tourette Syndrome Information Page See a list ... by: Office of Communications and Public Liaison National Institute of Neurological Disorders ...

  2. Rett Syndrome

    MedlinePlus

    ... binding protein 2 (MeCP2), which is needed for brain development and acts as one of the many biochemical ... the following criteria do not have Rett syndrome: brain injury secondary to ... abnormal psychomotor development in the first 6 months of life. Is ...

  3. Tourette Syndrome

    MedlinePlus

    ... organizations can help kids learn how to explain tics to others. How Should I Act Around Someone Who Has It? Kids who have Tourette syndrome want to be treated like everybody else. They can do regular stuff, just like other kids. In fact, Tim Howard grew up to be a soccer star. ...

  4. Caplan syndrome

    MedlinePlus

    ... who have breathed in mining dust that contains coal. This lung disease is also called coal worker's pneumoconiosis . ... Caplan syndrome is caused by breathing in coal mining dust. This ... of many small lumps in the lungs and an airway disease similar ...

  5. Rett Syndrome.

    ERIC Educational Resources Information Center

    Culbert, Linda A.

    This pamphlet reviews the historical process involved in initially recognizing Rett Syndrome as a specific disorder in girls. Its etiology is unknown, but studies have considered factors as hyperammonemia, a two-step mutation, a fragile X chromosome, metabolic disorder, environmental causation, dopamine deficiency, and an inactive X chromosome.…

  6. Overtraining syndrome.

    PubMed Central

    Budgett, R

    1990-01-01

    This review discusses the overtraining syndrome which is characterized by fatigue and underperformance precipitated by stress of training. Other stresses, depression and an increased susceptibility to infections may be important. Treatment requires rest and a stress management program over 3 months. PMID:2097018

  7. Aicardi syndrome

    MedlinePlus

    ... rare cases, one of these features may be missing (especially lack of development of the corpus callosum). Tests to diagnose Aicardi syndrome include: CT scan of the head EEG Eye exam MRI Other procedures and tests may be done, depending on the person.

  8. Sotos syndrome.

    PubMed

    Baujat, Geneviève; Cormier-Daire, Valérie

    2007-01-01

    Sotos syndrome is an overgrowth condition characterized by cardinal features including excessive growth during childhood, macrocephaly, distinctive facial gestalt and various degrees of learning difficulty, and associated with variable minor features. The exact prevalence remains unknown but hundreds of cases have been reported. The diagnosis is usually suspected after birth because of excessive height and occipitofrontal circumference (OFC), advanced bone age, neonatal complications including hypotonia and feeding difficulties, and facial gestalt. Other inconstant clinical abnormalities include scoliosis, cardiac and genitourinary anomalies, seizures and brisk deep tendon reflexes. Variable delays in cognitive and motor development are also observed. The syndrome may also be associated with an increased risk of tumors. Mutations and deletions of the NSD1 gene (located at chromosome 5q35 and coding for a histone methyltransferase implicated in transcriptional regulation) are responsible for more than 75% of cases. FISH analysis, MLPA or multiplex quantitative PCR allow the detection of total/partial NSD1 deletions, and direct sequencing allows detection of NSD1 mutations. The large majority of NSD1 abnormalities occur de novo and there are very few familial cases. Although most cases are sporadic, several reports of autosomal dominant inheritance have been described. Germline mosaicism has never been reported and the recurrence risk for normal parents is very low (<1%). The main differential diagnoses are Weaver syndrome, Beckwith-Wiedeman syndrome, Fragile X syndrome, Simpson-Golabi-Behmel syndrome and 22qter deletion syndrome. Management is multidisciplinary. During the neonatal period, therapies are mostly symptomatic, including phototherapy in case of jaundice, treatment of the feeding difficulties and gastroesophageal reflux, and detection and treatment of hypoglycemia. General pediatric follow-up is important during the first years of life to allow detection

  9. Cronkhite- Canada syndrome; a case report and review of the literature

    PubMed Central

    Safari, Mohammad Taghi; Shahrokh, Shabnam; Ebadi, Shahram; Sadeghi, Amir

    2016-01-01

    Cronkhite- Canada syndrome (CCS) considered as a rare and non-hereditary disorder. Gastrointestinal polyposis and diarrhea along with some extra signs and symptoms such as hypoproteinemia, and epidermal manifestations are recognized in this syndrome. The pathophysiology of this syndrome is not completely understood and it seems that inflammatory processes may be involved. We present a 50 year-old man with hamartomatous polyps throughout the colon and long-lasting diarrhea not responding to typical therapies during three years. PMID:26744616

  10. Theories of schizophrenia: a genetic-inflammatory-vascular synthesis

    PubMed Central

    Hanson, Daniel R; Gottesman, Irving I

    2005-01-01

    Background Schizophrenia, a relatively common psychiatric syndrome, affects virtually all brain functions yet has eluded explanation for more than 100 years. Whether by developmental and/or degenerative processes, abnormalities of neurons and their synaptic connections have been the recent focus of attention. However, our inability to fathom the pathophysiology of schizophrenia forces us to challenge our theoretical models and beliefs. A search for a more satisfying model to explain aspects of schizophrenia uncovers clues pointing to genetically mediated CNS microvascular inflammatory disease. Discussion A vascular component to a theory of schizophrenia posits that the physiologic abnormalities leading to illness involve disruption of the exquisitely precise regulation of the delivery of energy and oxygen required for normal brain function. The theory further proposes that abnormalities of CNS metabolism arise because genetically modulated inflammatory reactions damage the microvascular system of the brain in reaction to environmental agents, including infections, hypoxia, and physical trauma. Damage may accumulate with repeated exposure to triggering agents resulting in exacerbation and deterioration, or healing with their removal. There are clear examples of genetic polymorphisms in inflammatory regulators leading to exaggerated inflammatory responses. There is also ample evidence that inflammatory vascular disease of the brain can lead to psychosis, often waxing and waning, and exhibiting a fluctuating course, as seen in schizophrenia. Disturbances of CNS blood flow have repeatedly been observed in people with schizophrenia using old and new technologies. To account for the myriad of behavioral and other curious findings in schizophrenia such as minor physical anomalies, or reported decreased rates of rheumatoid arthritis and highly visible nail fold capillaries, we would have to evoke a process that is systemic such as the vascular and immune/inflammatory

  11. Mouth and genital ulcers with inflamed cartilage (MAGIC) syndrome complicated by aneurysmal aortitis.

    PubMed

    Ng, Chin Soon; Hogan, Patrick; McKenzie, Scott; Gibbs, Harry; Strutton, Geoff; Wong, Richard

    2007-08-01

    "MAGIC syndrome" (Mouth And Genital ulcers with Inflamed Cartilage) has been proposed to describe patients with clinical features of both relapsing polychondritis and Behcet disease. A total of 18 cases have been reported with only 1 case associated with aneurysmal aortitis described in 1997. Herein, we describe a patient with MAGIC syndrome complicated by aneurysmal aortitis requiring cardiothoracic surgery and intensive immunosuppression. Monitoring for the possible development of inflammatory aortic aneurysms should thus be considered in patients with MAGIC syndrome who have persistently elevated serum inflammatory markers. If an aortic aneurysm is detected, cardiothoracic surgical referral is necessary, close monitoring for enlargement is mandatory, and intensification of immunosuppressive therapy should be considered.

  12. Spinal MRI Findings of Guillain-Barré Syndrome

    PubMed Central

    Alkan, Ozlem; Yildirim, Tulin; Tokmak, Naime; Tan, Meliha

    2009-01-01

    Guillain-Barré syndrome is a relatively common, acute, and rapidly progressive, inflammatory demyelinating polyneuropathy. The diagnosis is usually established on the basis of symptoms and signs, aided by cerebrospinal fluid findings and electrophysiologic criteria. Previously, radiologic examinations have been used only to rule out other spinal abnormalities. We report a case of systemic lupus erythematosus associated with Guillain-Barré syndrome with marked enhancement of nerve roots of the conus medullaris and cauda equina on MR imaging. These MR observations may help confirm the diagnosis of Guillain-Barré syndrome. PMID:22470650

  13. Multimodal Imaging of the White Dot Syndromes and Related Diseases

    PubMed Central

    Knickelbein, Jared E; Sen, H Nida

    2016-01-01

    The white dot syndromes encompass a group of rare posterior uveitis conditions that are characterized by outer retinal and/or choroidal hypopigmented lesions that are thought to be inflammatory in nature. The size, shape, and location of lesions in the fundus aid in differentiating these conditions. Multimodal imaging, including modalities such as fundus autofluorescence, optical coherence tomography, fluorescein angiography, and indocyanine green angiography, among others, has become integral in diagnosing and monitoring many of the white dot syndromes. Furthermore, multimodal imaging modalities have provided insights into the pathogenesis and exact sites within the retina and choroid affected by white dot syndromes. PMID:27482471

  14. The Source for Syndromes.

    ERIC Educational Resources Information Center

    Richard, Gail J.; Hoge, Debra Reichert

    Designed for practicing speech-language pathologists, this book discusses different syndrome disabilities, pertinent speech-language characteristics, and goals and strategies to begin intervention efforts at a preschool level. Chapters address: (1) Angelman syndrome; (2) Asperger syndrome; (3) Down syndrome; (4) fetal alcohol syndrome; (5) fetal…

  15. Pregnancy and inflammatory bowel disease.

    PubMed

    Zeldis, J B

    1989-08-01

    Conclusions about the relationship between the pathophysiology and treatment of inflammatory bowel disease and the physiology and management of pregnancy are based on the results of several large physician surveys and retrospective chart reviews. Patients with active disease fare worse than those with inactive disease. There is little evidence that pregnancy affects the course of inflammatory bowel disease or that inactive inflammatory bowel disease affects the course of pregnancy. Judicious medical therapy is effective in controlling inflammatory bowel disease during pregnancy. Sulfasalazine or steroid therapy should not be withdrawn in a patient who needs it to achieve or maintain a quiescent state of inflammatory bowel disease during the course of pregnancy. Immunosuppressive therapy should be avoided. Aggressive medical therapy with total parenteral nutrition in a team approach with a gastroenterologist, surgeon, and perinatologist usually avoids the need for surgical intervention during pregnancy with a good fetal outcome in a patient whose disease is active. Contraception against pregnancy need only be considered in those patients whose disease is so severe that operative therapy is imminent.

  16. Phytoestrogens and the metabolic syndrome.

    PubMed

    Jungbauer, Alois; Medjakovic, Svjetlana

    2014-01-01

    Phytoestrogens are a diverse class of non-steroidal compounds that have an affinity for estrogen receptors α and β, for the peroxisome proliferator-activated receptor (PPAR) family and for the aryl hydrocarbon receptor. Examples of phytoestrogens include prenylated flavonoids, isoflavones, coumestans and lignans. Many phytoestrogens counteract the cellular derailments that are responsible for the development of metabolic syndrome. Here we propose a mechanism of action which is based on five pillars/principles. First, phytoestrogens are involved in the downregulation of pro-inflammatory cytokines, such as COX-2 and iNOS, by activating PPAR and by inhibiting IκB activation. Second, they increase reverse cholesterol transport, which is mediated by PPARγ. Third, phytoestrogens increase insulin sensitivity, which is mediated via PPARα. Fourth, they exert antioxidant effects by activating antioxidant genes through KEAP. Fifth, phytoestrogens increase energy expenditure by affecting AMP-activated kinase signaling cascades, which are responsible for the inhibition of adipogenesis. In addition to these effects, which have been demonstrated in vivo and in clinical trials, other effects, such as eNOS activation, may also be important. Some plant extracts from soy, red clover or licorice can be described as panPPAR activators. Fetal programming for metabolic syndrome has been hypothesized; thus, the consumption of dietary phytoestrogens during pregnancy may be relevant. Extracts from soy, red clover or licorice oil have potential as plant-derived medicines that could be used to treat polycystic ovary syndrome, a disease linked to hyperandrogenism and obesity, although clinical trials have not yet been conducted. Phytoestrogens may help prevent metabolic syndrome, although intervention studies will be always be ambiguous, because physical activity and reduced calorie consumption also have a significant impact. Nevertheless, extracts rich in phytoestrogens may be an

  17. Marine Bioactives: Pharmacological Properties and Potential Applications against Inflammatory Diseases

    PubMed Central

    D’Orazio, Nicolantonio; Gammone, Maria Alessandra; Gemello, Eugenio; De Girolamo, Massimo; Cusenza, Salvatore; Riccioni, Graziano

    2012-01-01

    Inflammation is a hot topic in medical research, because it plays a key role in inflammatory diseases: rheumatoid arthritis (RA) and other forms of arthritis, diabetes, heart diseases, irritable bowel syndrome, Alzheimer’s disease, Parkinson’s disease, allergies, asthma, even cancer and many others. Over the past few decades, it was realized that the process of inflammation is virtually the same in different disorders, and a better understanding of inflammation may lead to better treatments for numerous diseases. Inflammation is the activation of the immune system in response to infection, irritation, or injury, with an influx of white blood cells, redness, heat, swelling, pain, and dysfunction of the organs involved. Although the pathophysiological basis of these conditions is not yet fully understood, reactive oxygen species (ROS) have often been implicated in their pathogenesis. In fact, in inflammatory diseases the antioxidant defense system is compromised, as evidenced by increased markers of oxidative stress, and decreased levels of protective antioxidant enzymes in patients with rheumatoid arthritis (RA). An enriched diet containing antioxidants, such as vitamin E, vitamin C, β-carotene and phenolic substances, has been suggested to improve symptoms by reducing disease-related oxidative stress. In this respect, the marine world represents a largely untapped reserve of bioactive ingredients, and considerable potential exists for exploitation of these bioactives as functional food ingredients. Substances such as n-3 oils, carotenoids, vitamins, minerals and peptides provide a myriad of health benefits, including reduction of cardiovascular diseases, anticarcinogenic and anti-inflammatory activities. New marine bioactives are recently gaining attention, since they could be helpful in combating chronic inflammatory degenerative conditions. The aim of this review is to examine the published studies concerning the potential pharmacological properties and

  18. Divergent gastrointestinal stromal tumors in syndromic settings.

    PubMed

    Ricci, Riccardo; Martini, Maurizio; Cenci, Tonia; Riccioni, Maria Elena; Maria, Giorgio; Cassano, Alessandra; Larocca, Luigi Maria

    2016-01-01

    The vast majority of gastrointestinal stromal tumors (GISTs) occur as sporadic tumors. Rarely, however, these neoplasms can arise in syndromic contexts. Under these circumstances, GISTs are often multiple and associated with accompanying signs peculiar of the hosting syndrome. Moreover, syndromic GISTs themselves tend to show heterogeneous features depending on the underlying condition. Multiple inflammatory fibroid polyps (IFPs) and a jejunal spindle-cell GIST were resected in a germline PDGFRA-mutant individual. Although the association of IFP and GIST is typical of this genetic setting (PDGFRA mutations can in fact trigger both these tumor types), PDGFRA-mutant GISTs are usually epithelioid and gastric. This discrepancy was settled evidencing a somatic KIT mutation in the GIST. The awareness of possible somatic mutations can be critical in the management of high-risk/malignant GISTs arising in syndromic settings. GIST features unusual for a given GIST-predisposing syndrome are a valuable tool in the hands of physicians for suspecting these "extra" triggers, which could not be sought for once a diagnosis of GIST-prone syndrome is well established, in a bona fide cost/benefit perspective. PMID:27318444

  19. Recent advances in primary Sjogren's syndrome

    PubMed Central

    Holdgate, Nicholas; St.Clair, E. Wiliam

    2016-01-01

    Primary Sjögren’s syndrome, a chronic inflammatory process, is among the most commonly occurring rheumatologic diseases. The clinical hallmark of this disease is exocrine gland dysfunction, resulting predominately in dry eyes and dry mouth. However, the disease often extends beyond the exocrine glands to seriously affect other organs systems, such as the lungs, kidneys, and nervous system. Moreover, patients with primary Sjögren’s syndrome develop non-Hodgkin’s B cell lymphoma at a substantially higher rate than the general population. New research has improved our understanding of disease mechanisms, with notable advances in our knowledge about the genetic susceptibility of disease, the molecular details of the chronic inflammatory response in the salivary glands, and the complex role of the type 1 interferon pathway. The pipeline of drugs under development for the treatment of primary Sjögren’s syndrome is enriched with novel biologics and small molecular entities targeting the pathogenic process. Herein, we summarize the latest advances in elucidating the pathogenesis of primary Sjögren’s syndrome and highlight new drugs in clinical development aiming to reverse the glandular dysfunction and favorably impact the systemic features of this disease. PMID:27347394

  20. Periodic fevers and autoinflammatory syndromes in childhood.

    PubMed

    Ostring, Genevieve T; Singh-Grewal, Davinder

    2016-09-01

    Recurrent fever is a common presentation in paediatric practice and can be caused by a wide variety of diseases including autoinflammatory conditions. The innate immune system plays an essential role in the 'first line' response to infection through mediation of inflammatory responses. Inflammasomes are part of the regulatory process for this system and result in the production of the powerful pro-inflammatory cytokine interleukin-1B. Dysregulation of inflammasomes, and Interleukin 1 production, contributes to the pathogenesis of autoinflammatory diseases. This review focuses on described periodic fever syndromes (PFS) which are now collectively referred to as autoinflammatory syndromes. Conditions discussed include periodic fever aphthous stomatitis pharyngitis and cervical adenopathy, familial Mediterranean fever, tumour necrosis factor receptor-associated periodic syndromes, hyperimmunoglobulinaemia D and the cryopyrin-associated periodic syndromes. Presenting features, complications, diagnostic and treatment approaches for these conditions are discussed. Nonetheless, as most of these conditions are rare and may have significant long-term complications, it is recommended that they be managed in consultations with a physician experienced in managing PFS. PMID:27650143

  1. Transcriptional Control of Inflammatory Responses

    PubMed Central

    Smale, Stephen T.; Natoli, Gioacchino

    2014-01-01

    The inflammatory response requires the activation of a complex transcriptional program that is both cell-type- and stimulus-specific and involves the dynamic regulation of hundreds of genes. In the context of an inflamed tissue, extensive changes in gene expression occur in both parenchymal cells and infiltrating cells of the immune system. Recently, basic transcriptional mechanisms that control inflammation have been clarified at a genome scale, particularly in macrophages and conventional dendritic cells. The regulatory logic of distinct groups of inflammatory genes can be explained to some extent by identifiable sequence-encoded features of their chromatin organization, which impact on transcription factor (TF) accessibility and impose different requirements for gene activation. Moreover, it has become apparent that the interplay between TFs activated by inflammatory stimuli and master regulators exerts a crucial role in controlling cell-type-specific transcriptional outputs. PMID:25213094

  2. Obesity, adipokines and metabolic syndrome in polycystic ovary syndrome.

    PubMed

    Carmina, Enrico

    2013-01-01

    The complex mechanisms linking fat excess to metabolic syndrome are not well understood, but several experimental studies have shown that altered production of adipokines plays a main role in development and progression of this disorder. In particular, reduced secretion of adiponectin has a crucial role in inducing insulin resistance but also in determining the clustering of elevated triglycerides and small, dense LDL particles. Increased leptin secretion may be responsible for sympathetic nervous system overactivity and hypertension, while reduced omentin may have an important permissive role in the development of atherogenic processes. Finally, cytokines and other adipokines (resistin, visfatin) determine and modulate the inflammatory process that is an essential component of this condition of cardiovascular risk. Because obesity is prevalent in polycystic ovary syndrome (PCOS), it is not surprising that patients with PCOS present altered adipokine levels and increased prevalence of metabolic syndrome. However, because of the presence of other CV risk factors (androgen excess), in PCOS adipokine dysfunction is particularly severe. Understanding and treating adipokine dysfunction in young women with PCOS is an essential component of any politics of prevention of CV diseases in the general population.

  3. Paraneoplastic syndromes

    SciTech Connect

    Weller, R.E.

    1994-03-01

    Paraneoplastic syndromes (PNS) comprise a diverse group of disorders that are associated with cancer but unrelated to the size, location, metastases, or physiologic activities of the mature tissue of origin. They are remote effects of tumors that may appear as signs, symptoms, or syndromes which can mimic other disease conditions encountered in veterinary medicine. Recognition of PNS is valuable for several reasons: the observed abnormalities may represent tumor cell markers and facilitate early diagnosis of the tumor; they may allow assessment of premalignant states; they may aid in the search metastases; they may help quantify and monitor response to therapy; and, they may provide insight into the study of malignant transformation and oncogene expression. This review will concentrate on the pathophysiology, diagnosis, and treatment of some of the common PNS encountered in veterinary medicine.

  4. Fluency Disorders in Genetic Syndromes

    ERIC Educational Resources Information Center

    Van Borsel, John; Tetnowski, John A.

    2007-01-01

    The characteristics of various genetic syndromes have included "stuttering" as a primary symptom associated with that syndrome. Specifically, Down syndrome, fragile X syndrome, Prader-Willi syndrome, Tourette syndrome, Neurofibromatosis type I, and Turner syndrome all list "stuttering" as a characteristic of that syndrome. An extensive review of…

  5. [Fibromyalgia syndrome].

    PubMed

    Naranjo Hernández, A; Rodríguez Lozano, C; Ojeda Bruno, S

    1992-02-01

    The Fibromialgia Syndrome (FS) is a common clinical entity which may produce symtoms and signs related to multiple fields of Medicine. Typical clinical characteristics of FS include extensive pain, presence of sensitive points during exploration, morning stiffness, asthenia and non-refresing sleep. Frequently, associated rheumatologic diseases are observed, as rheumatoid arthritis, osteoarthrosis and vertebral disorders. In FS, complementary tests are usually normal. The most widely accepted hypothesis suggests that this is a disorder affecting modulation of pain sensitivity.

  6. Lemierre's syndrome and genetic polymorphisms: a case report

    PubMed Central

    Constantin, Jean-Michel; Mira, Jean-Paul; Guerin, Renaud; Cayot-Constantin, Sophie; Lesens, Olivier; Gourdon, Florence; Romaszko, Jean-Pierre; Linval, Philippe; Laurichesse, Henri; Bazin, Jean-Etienne

    2006-01-01

    Background Lemierre's syndrome presents a classic clinical picture, the pathophysiology of which remains obscure. Attempts have been made to trace genetic predispositions that modify the host detection of pathogen or the resultant systemic reaction. Case presentation A 17-year old female, with no previous medical history, was admitted to the intensive care unit for septic shock, acute respiratory distress syndrome and Lemierre's syndrome. Her DNA was assayed for single nucleotide polymorphisms previously incriminated in the detection of the pathogen, the inflammatory response and the coagulation cascade. We observed functional variations in her Toll like 5 receptor (TLR 5) gene and two coagulation variations (Tissue Factor (TF) 603 and Plasminogen-Activator-Inhibitor-1 (PAI-1) 4G-4G homozygosity) associated with thrombotic events. Conclusion The innate immune response and the prothrombogenic mutations could explain, at least in part, the symptoms of Lemierre's syndrome. Genomic study of several patients with Lemierre's syndrome may reveal its pathophysiology. PMID:16846490

  7. Pro-/Anti-inflammatory Dysregulation in Patients With First Episode of Psychosis: Toward an Integrative Inflammatory Hypothesis of Schizophrenia

    PubMed Central

    García-Bueno, Borja; Bioque, Miquel; Mac-Dowell, Karina S.; Barcones, M. Fe; Leza, Juan C.

    2014-01-01

    Background: Schizophrenia is a chronic syndrome of unknown etiology, predominantly defined by signs of psychosis. The onset of the disorder occurs typically in late adolescence or early adulthood. Efforts to study pathophysiological mechanisms in early stages of the disease are crucial in order to prompt intervention. Methods: Case-control study of first-episode psychotic (FEP) patients and matched controls. We recruited 117 patients during the first year after their FEP according to the DSM-IV criteria and recruited 106 gender-, race-, and age-matched controls between September 2010 and June 2011. Results: Biochemical studies carried out in peripheral mononuclear blood cells (PMBC) and plasma evidence a significant increase in intracellular components of a main proinflammatory pathway, along with a significant decrease in the anti-inflammatory ones. Multivariate logistic regression analyses identified the expression of inducible isoforms of nitric oxide synthase and cyclooxygenase in PMBC and homocysteine plasma levels as the most reliable potential risk factors and the inhibitor of the inflammatory transcription factor NFκB, IκBα, and the anti-inflammatory prostaglandin 15d-PGJ2 as potential protection factors. Discussion: Taken as a whole, the results of this study indicate robust phenotypical differences at the cellular machinery level in PMBC of patients with FEP. Although more scientific evidence is needed, the determination of multiple components of pro- and anti-inflammatory cellular pathways including the activity of nuclear receptors has interesting potential as biological markers and potential risk/protective factors for FEP. Due to its soluble nature, a notable finding in this study is that the anti-inflammatory mediator 15d-PGJ2 might be used as plasmatic biomarker for first episodes of psychosis. PMID:23486748

  8. Heart and Down Syndrome

    MedlinePlus

    ... Associated Conditions » The Heart & Down Syndrome The Heart & Down Syndrome Abnormalities of the cardiovascular system are common in ... the Most Common Heart Defects in Children With Down Syndrome? The most common defects are Atrioventricular Septal Defect ( ...

  9. What is Down Syndrome?

    MedlinePlus

    ... NICHD Research Information Clinical Trials Resources and Publications Down Syndrome: Condition Information Skip sharing on social media links Share this: Page Content What is Down syndrome? Down syndrome describes a set of cognitive and ...

  10. Tethered Spinal Cord Syndrome

    MedlinePlus

    ... Enhancing Diversity Find People About NINDS NINDS Tethered Spinal Cord Syndrome Information Page Table of Contents (click to ... being done? Clinical Trials Organizations What is Tethered Spinal Cord Syndrome? Tethered spinal cord syndrome is a neurological ...

  11. Reye syndrome - resources

    MedlinePlus

    Resources - Reye syndrome ... The following organizations are good resources for information on Reye Syndrome : National Reye's Syndrome Foundation, Inc. -- www.reyessyndrome.org National Institute of Neurologic Disorders and Stroke -- www. ...

  12. Paraneoplastic syndromes

    SciTech Connect

    Weller, R.E.

    1986-10-01

    Paraneoplastic syndromes (PNS) comprise a diverse group of disorders that are associated with cancer but unrelated to the size, location, metastases, or physiologic activities of the mature tissue of origin. They are remote effects of tumors that may appear as signs, symptoms or syndromes which can mimic other disease conditions encountered in veterinary medicine. Various types of PNS, singly or in multiples, may be associated with either benign or malignant tumors and may involve almost every organ system, directly or indirectly. These disorders can precede the discovery of the tumor by weeks, months, or even years, and many are good diagnostic and prognostic indicators. The true incidence of PNS in animal cancer patients is unknown, although approximately 75% of all human cancer patients, at some time during the tumor-bearing part of their lives, suffer from one or more of these disorders. Recognition of PNS is valuable because the observed abnormalities may represent tumor cell markers and facilitate early diagnosis of the tumor, because they may allow assessment of premalignant states, because they may aid in the search for metastases, because they may help quantify and monitor response to therapy, and because they may provide insight into the study of malignant transformations and oncogene expression. Recognition of these syndromes is relevant to the diagnosis and treatment of many problems in veterinary cancer medicine. 22 refs., 2 tabs.

  13. Acrodysostosis syndromes.

    PubMed

    Silve, C; Le-Stunff, C; Motte, E; Gunes, Y; Linglart, A; Clauser, E

    2012-01-01

    Acrodysostosis (ADO) refers to a heterogeneous group of rare skeletal dysplasia that share characteristic features including severe brachydactyly, facial dysostosis and nasal hypoplasia. The literature describing acrodysostosis cases has been confusing because some reported patients may have had other phenotypically related diseases presenting with Albright Hereditary Osteodystrophy (AHO) such as pseudohypoparathyroidism type 1a (PHP1a) or pseudopseudohypoparathyroidism (PPHP). A question has been whether patients display or not abnormal mineral metabolism associated with resistance to PTH and/or resistance to other hormones that bind G-protein coupled receptors (GPCR) linked to Gsα, as observed in PHP1a. The recent identification in patients affected with acrodysostosis of defects in two genes, PRKAR1A and PDE4D, both important players in the GPCR-Gsα-cAMP-PKA signaling, has helped clarify some issues regarding the heterogeneity of acrodysostosis, in particular the presence of hormonal resistance. Two different genetic and phenotypic syndromes are now identified, both with a similar bone dysplasia: ADOHR, due to PRKAR1A defects, and ADOP4 (our denomination), due to PDE4D defects. The existence of GPCR-hormone resistance is typical of the ADOHR syndrome. We review here the PRKAR1A and PDE4D gene defects and phenotypes identified in acrodysostosis syndromes, and discuss them in view of phenotypically related diseases caused by defects in the same signaling pathway. PMID:24363928

  14. CUSHING'S SYNDROME

    PubMed Central

    Wilkinson, Allan B.

    1961-01-01

    Sixteen cases of verified Cushing's syndrome, and twelve cases of probable Cushing's syndrome were reviewed and data on them were compared with various reports on Cushing's syndrome in the literature. The diagnosis hinges upon a high index of suspicion, and one or several of the major criteria may be lacking. Ultimate establishment of correct diagnosis should be based largely on the clinical features, although stimulation and suppression tests may help to confirm a clinical diagnosis. In well-established clinical cases, with borderline laboratory confirmation, exploration may be justified, especially if tests fail to identify a specific cause. In cases of adrenal cortical tumor, all pathological tissue should be removed if possible, with great care to support and stimulate the remaining atrophic adrenal gland during and following operation. In cases of bilateral adrenal cortical hyperplasia, the problem is one of how much to remove. At present most investigators advocate radical subtotal resection, leaving less than 10 per cent of one side. ImagesFigure 1.Figure 2.Figure 3.Figure 4.Figure 5.Figure 6. PMID:13785315

  15. Nutcracker syndrome

    PubMed Central

    Gulleroglu, Kaan; Gulleroglu, Basak; Baskin, Esra

    2014-01-01

    The nutcracker phenomenon [left renal vein (LRV) entrapment syndrome] refers to compression of the LRV most commonly between abdominal aorta and superior mesenteric artery. Term of nutcracker syndrome (NCS) is used for patients with clinical symptoms associated with nutcracker anatomy. LRV entrapment divided into 2 types: anterior and posterior. Posterior and right-sided NCSs are rare conditions. The symptoms vary from asymptomatic hematuria to severe pelvic congestion. Symptoms include hematuria, orthostatic proteinuria, flank pain, abdominal pain, varicocele, dyspareunia, dysmenorrhea, fatigue and orthostatic intolerance. Existence of the clinical features constitutes a basis for the diagnosis. Several imaging methods such as Doppler ultrasonography, computed tomography angiography, magnetic resonance angiography and retrograde venography are used to diagnose NCS. The management of NCS depends upon the clinical presentation and the severity of the LRV hypertension. The treatment options are ranged from surveillance to nephrectomy. Treatment decision should be based on the severity of symptoms and their expected reversibility with regard to patient’s age and the stage of the syndrome. PMID:25374822

  16. Nutcracker syndrome.

    PubMed

    Gulleroglu, Kaan; Gulleroglu, Basak; Baskin, Esra

    2014-11-01

    The nutcracker phenomenon [left renal vein (LRV) entrapment syndrome] refers to compression of the LRV most commonly between abdominal aorta and superior mesenteric artery. Term of nutcracker syndrome (NCS) is used for patients with clinical symptoms associated with nutcracker anatomy. LRV entrapment divided into 2 types: anterior and posterior. Posterior and right-sided NCSs are rare conditions. The symptoms vary from asymptomatic hematuria to severe pelvic congestion. Symptoms include hematuria, orthostatic proteinuria, flank pain, abdominal pain, varicocele, dyspareunia, dysmenorrhea, fatigue and orthostatic intolerance. Existence of the clinical features constitutes a basis for the diagnosis. Several imaging methods such as Doppler ultrasonography, computed tomography angiography, magnetic resonance angiography and retrograde venography are used to diagnose NCS. The management of NCS depends upon the clinical presentation and the severity of the LRV hypertension. The treatment options are ranged from surveillance to nephrectomy. Treatment decision should be based on the severity of symptoms and their expected reversibility with regard to patient's age and the stage of the syndrome.

  17. [Polyglandular autoimmune syndromes : An overview].

    PubMed

    Komminoth, P

    2016-05-01

    Polyglandular autoimmune syndromes (PGAS), also known as autoimmune polyendocrinopathy syndromes (APS), are a heterogeneous group of rare, genetically caused diseases of the immune system which lead to inflammatory damage of various endocrine glands resulting in malfunctions. In addition, autoimmune diseases of non-endocrine organs may also be found. Early diagnosis of PGAS is often overlooked because of heterogeneous symptoms and the progressive occurrence of the individual diseases. The two most important forms of PGAS are the juvenile and adult types. The juvenile type (PGAS type 1) is caused by mutations in the autoimmune regulator (AIRE) gene on chromosome 21, exhibits geographic variations in incidence and is defined by the combination of mucocutaneous candidiasis, Addison's disease and hypoparathyroidism. In addition, autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome and other autoimmune diseases can also occur. The adult form of PGAS (PGAS type 2) is a multigenetic disorder associated with some HLA haplotypes, is more common than the juvenile type, shows female predominance and exhibits the combination of type 1 diabetes, autoimmune thyroid disease, Addison's disease and other autoimmune disorders. The histological alterations in affected organs of PGAS patients are similar to findings in sporadically occurring autoimmune diseases of these organs but there are no pathognomic fine tissue findings. If patients exhibit autoimmune changes in two different endocrine glands or if there are indications of several autoimmune disorders from the patient history, it is important to consider PGAS and inform the clinicians of this suspicion.

  18. [Post-Lyme disease syndrome].

    PubMed

    Błaut-Jurkowska, Justyna; Jurkowski, Marcin

    2016-02-01

    Lyme disease is a chronic infectious disease caused by the bacteria, spirochete of the Borrelia type. Skin, nervous system, musculoskeletal system and heart may be involved in the course of the disease. The prognosis for properly treated Lyme disease is usually good. However, in about 5% of patients so called Post-Lyme disease syndrome (PLSD) develops. It is defined as a syndrome of subjective symptoms persisting despite proper treatment of Borrelia burgdorferi infection. The most common symptoms include: fatigue, muscle and joint pain, and problems with memory and concentration. Pathogenesis of PLDS remains unknown. The differential diagnosis should include neurological, rheumatic and mental diseases. Till now there is no causative treatment of PLDS. In relieving symptom rehabilitation, painkillers, anti-inflammatory and antidepressants medicines are recommended. Emotional and psychological supports are also necessary. Non-specific symptoms reported by patients with post- Lyme disease syndrome raise the suspicion of other pathologies. This can lead to misdiagnosis and implementation of unnecessary, potentially harmful to the patient's therapy. An increase in tick-borne diseases needs to increase physicians awareness of these issues.

  19. [Post-Lyme disease syndrome].

    PubMed

    Błaut-Jurkowska, Justyna; Jurkowski, Marcin

    2016-02-01

    Lyme disease is a chronic infectious disease caused by the bacteria, spirochete of the Borrelia type. Skin, nervous system, musculoskeletal system and heart may be involved in the course of the disease. The prognosis for properly treated Lyme disease is usually good. However, in about 5% of patients so called Post-Lyme disease syndrome (PLSD) develops. It is defined as a syndrome of subjective symptoms persisting despite proper treatment of Borrelia burgdorferi infection. The most common symptoms include: fatigue, muscle and joint pain, and problems with memory and concentration. Pathogenesis of PLDS remains unknown. The differential diagnosis should include neurological, rheumatic and mental diseases. Till now there is no causative treatment of PLDS. In relieving symptom rehabilitation, painkillers, anti-inflammatory and antidepressants medicines are recommended. Emotional and psychological supports are also necessary. Non-specific symptoms reported by patients with post- Lyme disease syndrome raise the suspicion of other pathologies. This can lead to misdiagnosis and implementation of unnecessary, potentially harmful to the patient's therapy. An increase in tick-borne diseases needs to increase physicians awareness of these issues. PMID:27000820

  20. The Spectrum of Monogenic Autoinflammatory Syndromes: Understanding Disease Mechanisms and Use of Targeted Therapies

    PubMed Central

    Glaser, Rachel L.; Goldbach-Mansky, Raphaela

    2009-01-01

    Monogenic autoinflammatory diseases encompass a distinct and growing clinical entity of multisystem inflammatory diseases with known genetic defects in the innate immune system. The diseases present clinically with episodes of seemingly unprovoked inflammation (fever, rashes, and elevation of acute phase reactants). Understanding the genetics has led to discovery of new molecules involved in recognizing exogenous and endogenous danger signals, and the inflammatory response to these stimuli. These advances have furthered understanding of innate inflammatory pathways and spurred collaborative research in rheumatology and infectious diseases. The pivotal roles of interleukin (IL)-1β in cryopyrin-associated periodic syndromes, tumor necrosis factor (TNF) in TNF receptor-associated periodic syndrome, and links to inflammatory cytokine dysregulation in other monogenic autoinflammatory diseases have resulted in effective therapies targeting proinflammatory cytokines IL-1β and TNF and uncovered other new potential targets for anti-inflammatory therapies. PMID:18606080

  1. [Evaluation of anti-inflammatory activity of extracts from Siberian plants].

    PubMed

    Nesterova, Iu V; Povet'eva, T N; Aksinenko, S G; Suslov, N I; Gaĭdamovich, N N; Nagorniak, Iu G; Popova, E V; Kravtsova, S S; Andreeva, T I

    2009-01-01

    Experimental investigations have shown that water-alcohol extracts from plants containing alkaloids (Aconitum baikalense, Aconitum septentrionale, Delphinium elatum L., Conium maculatum) and salicylic acid (Filipendula ulmaria, Salix viminalis, Fragaria vesca, Rubus idaeus) inhibited the development of main symptoms of inflammation, viz. exudation, pain, fever, to the same extent as non-steroidal anti-inflammatory agents. The substances studied in this work may be used to develop new efficient pharmacological preparations for the treatment of different inflammatory conditions associated with severe pain syndrome.

  2. Paraneoplastic Necrotizing Myopathy with a Mild Inflammatory Component: A Case Report and Review of the Literature

    PubMed Central

    Wegener, Susanne; Bremer, Juliane; Komminoth, Paul; Jung, Hans H.; Weller, Michael

    2010-01-01

    Inflammatory myopathies such as dermatomyositis and polymyositis are well-recognized paraneoplastic syndromes. Little is known, however, about necrotizing myopathies in association with cancer. We here describe a case of paraneoplastic necrotizing myopathy with a mild inflammatory infiltrate in a patient with adenocarcinoma. After the rapid development of a severe, disabling muscle weakness, the patient experienced near complete recovery within 4 months under oral prednisone treatment. In the context of the presented case, we will review current knowledge about paraneoplastic necrotizing myopathies. PMID:20740165

  3. Absence of persistent infection with enteroviruses in muscles of patients with inflammatory myopathies.

    PubMed

    Leon-Monzon, M; Dalakas, M C

    1992-08-01

    We searched for enteroviral nucleic acid sequences using the polymerase chain reaction and slot-blot hybridization in coded muscle biopsy specimens from 39 patients with active inflammatory myopathies (polymyositis, dermatomyositis, and inclusion-body myositis) and from 16 patients with other neuromuscular diseases, including patients with postpolio syndrome. For primers, we used sequences of the noncoding region at the 5' end of the viral RNA. We failed to detect specific enteroviral nucleic acid sequences in the muscle biopsy specimens. Because this sensitive technique can amplify even low copy numbers of the viral genome, it appears unlikely that a persistent enteroviral infection is the cause of inflammatory myopathies.

  4. Inherited ichthyosis: Syndromic forms.

    PubMed

    Yoneda, Kozo

    2016-03-01

    Among diseases that cause ichthyosis as one of the symptoms, there are some diseases that induce abnormalities in organs other than the skin. Of these, diseases with characteristic signs are regarded as syndromes. Although these syndromes are very rare, Netherton syndrome, Sjögren-Larsson syndrome, Conradi-Hünermann-Happle syndrome, Dorfman-Chanarin syndrome, ichthyosis follicularis, atrichia and photophobia (IFAP) syndrome, and Refsum syndrome have been described in texts as representative ones. It is important to know the molecular genetics and pathomechanisms in order to establish an effective therapy and beneficial genetic counseling including a prenatal diagnosis.

  5. Proteus Syndrome Foundation

    MedlinePlus

    ... Criteria & FAQs Medical Research Glossary Donate Cash Donation Life Insurance Gift Matching Gift Stock Gift Sunshine Society Contact Privacy Policy Proteus Syndrome Foundation The Proteus Syndrome Foundation , a ...

  6. Preclinical Assessment of Inflammatory Pain.

    PubMed

    Muley, Milind M; Krustev, Eugene; McDougall, Jason J

    2016-02-01

    While acute inflammation is a natural physiological response to tissue injury or infection, chronic inflammation is maladaptive and engenders a considerable amount of adverse pain. The chemical mediators responsible for tissue inflammation act on nociceptive nerve endings to lower neuronal excitation threshold and sensitize afferent firing rate leading to the development of allodynia and hyperalgesia, respectively. Animal models have aided in our understanding of the pathophysiological mechanisms responsible for the generation of chronic inflammatory pain and allowed us to identify and validate numerous analgesic drug candidates. Here we review some of the commonly used models of skin, joint, and gut inflammatory pain along with their relative benefits and limitations. In addition, we describe and discuss several behavioral and electrophysiological approaches used to assess the inflammatory pain in these preclinical models. Despite significant advances having been made in this area, a gap still exists between fundamental research and the implementation of these findings into a clinical setting. As such we need to characterize inherent pathophysiological pathways and develop new endpoints in these animal models to improve their predictive value of human inflammatory diseases in order to design safer and more effective analgesics.

  7. Inflammatory process in Alzheimer's Disease

    PubMed Central

    Meraz-Ríos, Marco A.; Toral-Rios, Danira; Franco-Bocanegra, Diana; Villeda-Hernández, Juana; Campos-Peña, Victoria

    2013-01-01

    Alzheimer Disease (AD) is a neurodegenerative disorder and the most common form of dementia. Histopathologically is characterized by the presence of two major hallmarks, the intracellular neurofibrillary tangles (NFTs) and extracellular neuritic plaques (NPs) surrounded by activated astrocytes and microglia. NFTs consist of paired helical filaments of truncated tau protein that is abnormally hyperphosphorylated. The main component in the NP is the amyloid-β peptide (Aβ), a small fragment of 40–42 amino acids with a molecular weight of 4 kD. It has been proposed that the amyloid aggregates and microglia activation are able to favor the neurodegenerative process observed in AD patients. However, the role of inflammation in AD is controversial, because in early stages the inflammation could have a beneficial role in the pathology, since it has been thought that the microglia and astrocytes activated could be involved in Aβ clearance. Nevertheless the chronic activation of the microglia has been related with an increase of Aβ and possibly with tau phosphorylation. Studies in AD brains have shown an upregulation of complement molecules, pro-inflammatory cytokines, acute phase reactants and other inflammatory mediators that could contribute with the neurodegenerative process. Clinical trials and animal models with non-steroidal anti-inflammatory drugs (NSAIDs) indicate that these drugs may decrease the risk of developing AD and apparently reduce Aβ deposition. Finally, further studies are needed to determine whether treatment with anti-inflammatory strategies, may decrease the neurodegenerative process that affects these patients. PMID:23964211

  8. Inflammatory and atherosclerotic interactions in the depleted uremic patient.

    PubMed

    Stenvinkel, P

    2001-01-01

    Despite the improvements in dialysis technology, the cardiovascular mortality rate is still unacceptably high among dialysis patients. It is obvious that traditional risk factors, such as hypertension, chronic heart failure (CHF), dyslipidemia and diabetes mellitus, may account for a large part of the increased cardiovascular mortality rate in these patients. However, based on recent research it could be speculated that other, non-traditional risk factors might also contribute to the high cardiovascular mortality rate in dialysis patients. Chronic inflammation, as evidenced by increased levels of pro-inflammatory cytokines and C-reactive protein (CRP), is a common feature in dialysis patients and is associated with an increased cardiovascular morbidity and mortality. Indeed, elevated levels of pro-inflammatory cytokines (such as TNF-alpha, IL-1 and IL-6) may cause malnutrition and progressive atherosclerotic cardiovascular disease by several pathogenetic mechanisms, which will be discussed in this review. Based on the strong associations observed between malnutrition, inflammation and atherosclerosis in patients with chronic renal failure (CRF) we have proposed that these features constitute a specific syndrome (MIA), which carries a high mortality rate. As elevated levels of pro-inflammatory cytokines may play a central part in the vicious circle of malnutrition, inflammation and atherosclerosis, further research is needed to investigate whether or not different anti-cytokine treatment strategies may improve survival in dialysis patients.

  9. Resistin in idiopathic inflammatory myopathies

    PubMed Central

    2012-01-01

    Introduction The purpose of this study was to evaluate and compare the serum levels and local expression of resistin in patients with idiopathic inflammatory myopathies to controls, and to determine the relationship between resistin levels, inflammation and disease activity. Methods Serum resistin levels were determined in 42 patients with inflammatory myopathies and 27 healthy controls. The association among resistin levels, inflammation, global disease activity and muscle strength was examined. The expression of resistin in muscle tissues from patients with inflammatory myopathies and healthy controls was evaluated. Gene expression and protein release from resistin-stimulated muscle and mononuclear cells were assessed. Results In patients with inflammatory myopathies, the serum levels of resistin were significantly higher than those observed in controls (8.53 ± 6.84 vs. 4.54 ± 1.08 ng/ml, P < 0.0001) and correlated with C-reactive protein (CRP) levels (r = 0.328, P = 0.044) and myositis disease activity assessment visual analogue scales (MYOACT) (r = 0.382, P = 0.026). Stronger association was observed between the levels of serum resistin and CRP levels (r = 0.717, P = 0.037) as well as MYOACT (r = 0.798, P = 0.007), and there was a trend towards correlation between serum resistin and myoglobin levels (r = 0.650, P = 0.067) in anti-Jo-1 positive patients. Furthermore, in patients with dermatomyositis, serum resistin levels significantly correlated with MYOACT (r = 0.667, P = 0.001), creatine kinase (r = 0.739, P = 0.001) and myoglobin levels (r = 0.791, P = 0.0003) and showed a trend towards correlation with CRP levels (r = 0.447, P = 0.067). Resistin expression in muscle tissue was significantly higher in patients with inflammatory myopathies compared to controls, and resistin induced the expression of interleukins (IL)-1β and IL-6 and monocyte chemoattractant protein (MCP)-1 in mononuclear cells but not in myocytes. Conclusions The results of this study

  10. The circadian clock regulates inflammatory arthritis

    PubMed Central

    Hand, Laura E.; Hopwood, Thomas W.; Dickson, Suzanna H.; Walker, Amy L.; Loudon, Andrew S. I.; Ray, David W.; Bechtold, David A.; Gibbs, Julie E.

    2016-01-01

    There is strong diurnal variation in the symptoms and severity of chronic inflammatory diseases, such as rheumatoid arthritis. In addition, disruption of the circadian clock is an aggravating factor associated with a range of human inflammatory diseases. To investigate mechanistic links between the biological clock and pathways underlying inflammatory arthritis, mice were administered collagen (or saline as a control) to induce arthritis. The treatment provoked an inflammatory response within the limbs, which showed robust daily variation in paw swelling and inflammatory cytokine expression. Inflammatory markers were significantly repressed during the dark phase. Further work demonstrated an active molecular clock within the inflamed limbs and highlighted the resident inflammatory cells, fibroblast-like synoviocytes (FLSs), as a potential source of the rhythmic inflammatory signal. Exposure of mice to constant light disrupted the clock in peripheral tissues, causing loss of the nighttime repression of local inflammation. Finally, the results show that the core clock proteins cryptochrome (CRY) 1 and 2 repressed inflammation within the FLSs, and provide novel evidence that a CRY activator has anti-inflammatory properties in human cells. We conclude that under chronic inflammatory conditions, the clock actively represses inflammatory pathways during the dark phase. This interaction has exciting potential as a therapeutic avenue for treatment of inflammatory disease.—Hand, L. E., Hopwood, T. W., Dickson, S. H., Walker, A. L., Loudon, A. S. I., Ray, D. W., Bechtold, D. A., Gibbs, J. E. The circadian clock regulates inflammatory arthritis. PMID:27488122

  11. Morvan Syndrome

    PubMed Central

    Maskery, Mark; Chhetri, Suresh K.; Dayanandan, Rejith; Gall, Claire

    2016-01-01

    A 74-year-old gentleman was admitted to the regional neurosciences center with encephalopathy, myokymia, and dysautonomia. Chest imaging had previously identified an incidental mass in the anterior mediastinum, consistent with a primary thymic tumor. Antivoltage-gated potassium channel (anti-VGKC) antibodies were positive (titer 1273 pmol/L) and he was hypokalemic. Electromyogram and nerve conduction studies were in keeping with peripheral nerve hyperexcitability syndrome, and an electroencephalogram was consistent with encephalopathy. A diagnosis of Morvan syndrome was made, for which he was initially treated with high-dose steroids, followed by a 5-day course of intravenous immunoglobulin (IVIG) therapy. He also underwent thymectomy, followed by a postexcision flare of his symptoms requiring intensive care management. Further steroids, plasmapheresis, and IVIG achieved stabilization of his clinical condition, enabling transfer for inpatient neurorehabilitation. He was commenced on azathioprine and a prolonged oral steroid taper. A subsequent presumed incipient relapse responded well to further IVIG treatment. This case report documents a thymoma-associated presentation of anti-VGKC-positive Morvan syndrome supplemented by patient and carer narrative and video, both of which provide valuable further insights into this rare disorder. There are a limited number of publications surrounding this rare condition available in the English literature. This, combined with the heterogenous presentation, association with underlying malignancy, response to treatment, and prognosis, provides a diagnostic challenge. However, the association with anti-VGKC antibody-associated complexes and 2 recent case series have provided some scope for both accurate diagnosis and management. PMID:26740856

  12. Postgastrectomy syndromes.

    PubMed

    Brooke-Cowden, G L; Braasch, J W; Gibb, S P; Haggitt, R C; McDermott, W V

    1976-04-01

    Postgastrectomy syndromes requiring further operation are fortunately uncommon, as the symptoms are disabling and the results of corrective surgery are, at times, disappointing. Our sixty-six patients underwent a total of seventy-six procedures with forty-one successful results and thirty-five failures. Among the secessful group, only fourteen results were graded as excellent. (Table V.) Our experience, like that of others, demonstrates the necessity of accurate evaluation of the patient and of accurate syndrome classification. This not only allows the appropriate operation to be chosen but also helps to indicate those in whom operation should be avoided. Where more than one surgically remediable syndrome exists, simultaneous correction should be undertaken. Treatment of the mechanical problems of obstructed afferent loop by jejunojejunostomy and of stomal obstruction by complete stomal reconstruction provides satisfactory results. Roux-en-Y anastomosis is effective in patients with alkaline gastritis, but we caution against the use of this procedure in patients with vague symptoms and minimal endoscopic changes. Antiperistaltic jejunal reversal is the procedure of choice in managing severe postvagotomy diarrhea. Although most patients with dumping can be managed conservatively, a small number with severe symptoms and nutritional problems cannot and require further operation. Our experience with conversion from Billroth II to Billroth I and with isoperistaltic interposition, although minimal, has been reasonably satisfactory. Four groups of patients remain with symptoms of chronic vomiting, late postvagotomy atonic stomach, dumping "plus," and miscellaneous symptoms. These patients have complaints that are difficult to define and usually have poor results with further operations. We believe that surgery should be avoided in these patients and that conservative measures be continued.

  13. Inflammatory duodenal necrosis complicating gastroschisis

    PubMed Central

    Fouad, Dina; Lee, Geraint J.; Upadhyaya, Manasvi; Drake, David

    2016-01-01

    Babies with gastroschisis have an increased risk of necrotizing enterocolitis (NEC) that can lead to short bowel syndrome, a long-term parenteral nutrition requirement, and its associated complications. To our knowledge, this is the first case report of recurrent duodenal ischemia and necrosis associated with gastroschisis in the absence of NEC totalis. PMID:27695214

  14. Inflammatory duodenal necrosis complicating gastroschisis

    PubMed Central

    Fouad, Dina; Lee, Geraint J.; Upadhyaya, Manasvi; Drake, David

    2016-01-01

    Babies with gastroschisis have an increased risk of necrotizing enterocolitis (NEC) that can lead to short bowel syndrome, a long-term parenteral nutrition requirement, and its associated complications. To our knowledge, this is the first case report of recurrent duodenal ischemia and necrosis associated with gastroschisis in the absence of NEC totalis.

  15. Postmenopausal syndrome

    PubMed Central

    Dalal, Pronob K.; Agarwal, Manu

    2015-01-01

    Menopause is one of the most significant events in a woman's life and brings in a number of physiological changes that affect the life of a woman permanently. There have been a lot of speculations about the symptoms that appear before, during and after the onset of menopause. These symptoms constitute the postmenopausal syndrome; they are impairing to a great extent to the woman and management of these symptoms has become an important field of research lately. This chapter attempts to understand these symptoms, the underlying pathophysiology and the management options available. PMID:26330639

  16. Refeeding syndrome.

    PubMed

    Fuentebella, Judy; Kerner, John A

    2009-10-01

    Refeeding syndrome (RFS) is the result of aggressive enteral or parenteral feeding in a malnourished patient, with hypophosphatemia being the hallmark of this phenomenon. Other metabolic abnormalities, such as hypokalemia and hypomagnesemia, may also occur, along with sodium and fluid retention. The metabolic changes that occur in RFS can be severe enough to cause cardiorespiratory failure and death. This article reviews the pathophysiology, the clinical manifestations, and the management of RFS. The key to prevention is identifying patients at risk and being aware of the potential complications involved in rapidly reintroducing feeds to a malnourished patient.

  17. Tourette Syndrome

    PubMed Central

    Murray, T. J.

    1982-01-01

    Tourette syndrome (Gilles de la Tourette disease) is a disorder of involuntary muscular tics, vocalizations and compulsive behavior. The tics and muscle movements vary in form and course; the complex repetitive patterns are eventually replaced by other patterns. The vocalization may be in the form of sounds, words or profanities and sometimes echolalia, echopraxia and palilalia. The onset may be from age two to 15 but is usually between ages eight and 12. Recent studies suggest that there is a hypersensitivity of dopamine receptors. Most patients respond well to haloperidol, but other drugs that may be of value include clonidine, pimozide, fluphenazine and trifluoroperazine. PMID:21286050

  18. Robinow syndrome

    PubMed Central

    Suresh, SS

    2008-01-01

    Robinow syndrome is a rare autosomal recessive mesomelic dwarfism with just more than 100 cases reported in the literature so far. The lower extremity is spared with skeletal deformity usually confined to the forearm, hand, and the dorsal spine. Diagnosis is made easily in the early childhood by the typical “fetal facies” appearance, which disappears to a certain extent as the patient grows. The author reports two cases of this entity with vertebral segmentation defects, rib fusion, and typical severe brachymelia and facial features. PMID:19753239

  19. Functional Dyspepsia: Subtypes, Risk Factors, and Overlap with Irritable Bowel Syndrome in a Population of African Patients

    PubMed Central

    Nwokediuko, Sylvester Chuks; Ijoma, Uchenna; Obienu, Olive

    2012-01-01

    Background. Functional dyspepsia is the prototype functional gastrointestinal disorder. This study was designed to determine its prevalence, subtypes, and risk factors associated with the subtypes. Method. Patients with upper gastrointestinal symptoms who presented for endoscopy were administered a questionnaire containing the functional dyspepsia and irritable bowel syndrome modules of the Rome III diagnostic criteria. Results. Of 192 patients who had functional dyspepsia, epigastric pain syndrome, postprandial distress syndrome, and combination of the two subtypes accounted for 79.2%, 62.5%, and 50%, respectively. Multivariate analysis of the risk factors showed that independent predictors of postprandial distress syndrome were alcohol and irritable bowel syndrome while irritable bowel syndrome was independent predictor of epigastric pain syndrome. Alcohol, smoking, and use of nonsteroidal anti-inflammatory drugs were independent predictors of cooccurrence of postprandial distress syndrome and epigastric pain syndrome. Conclusion. Functional dyspepsia accounts for 62.5% of dyspepsia in a population of black African patients. Regarding symptomatology, epigastric pain syndrome, postprandial distress syndrome, and combination of the two subtypes account for 79.2%, 62.5%, and 50%, respectively. Risk factors for functional dyspepsia are irritable bowel syndrome, alcohol, smoking, and use of nonsteroidal anti-inflammatory drugs. PMID:23213327

  20. Inflammatory cytokines in pediatric obstructive sleep apnea

    PubMed Central

    Huang, Yu-Shu; Guilleminault, Christian; Hwang, Fang-Ming; Cheng, Chuan; Lin, Cheng-Hui; Li, Hsueh-Yu; Lee, Li-Ang

    2016-01-01

    Abstract Pediatric obstructive sleep apnea (OSA) is associated with chronic systemic inflammation and with cognitive impairments. This study aimed to investigate the status of proinflammatory cytokines, particularly interleukin 17 (IL-17) and interleukin 23 (IL-23) and cognition in pediatric OSA. Controls and OSA children participated in the study. Exclusion criteria were adenotonsillectomy, heart, neurological and severe psychiatric diseases, craniofacial syndromes, and obesity. Polysomnogram was followed by serum testing for inflammatory markers and neurocognitive tests such as continuous performance task (CPT) and Wisconsin card sorting test, questionnaires, analyses of plasma high-sensitivity C-reactive protein (HS-CRP), tumor necrosis factor alpha (TNF-α), interleukin 1 (IL-1), interleukin 6 (IL-6), IL-17, and IL-23. Seventy-nine, 4 to 12-year-old subjects in 2 groups ended the study: 47 nonobese OSA children (mean age = 7.84 ± 0.56 years, body mass index [BMI] = 16.95 ± 0.47 kg/m2, BMI z-score = 0.15 ± 0.21, and mean apnea–hypopnea index [AHI] = 9.13 ± 1.67 events/h) and 32 healthy control children (mean age = 7.02 ± 0.65 years, with BMI = 16.55 ± 0.58 kg/m2, BMI z-score = −0.12 ± 0.27, and mean AHI = 0.41 ± 0.07 event/h) were enrolled. Serum cytokine analyses showed significantly higher levels of HS-CRP, IL-17, and IL-23 in OSA children (P = 0.002, P = 0.024, and P = 0.047). Regression test showed significant influence of HS-CRP, TNF-α, IL-6, IL-17, and specifically IL-23, with the continuous performance test and Wisconsin card sorting test. OSA children have abnormal levels of IL-17, an interleukin related to T helper 17 cells, a T helper cell involved in development of autoimmunity and inflammation. This high expression level may contribute to the complications of pediatric OSA; we also found a significant influence of inflammatory cytokines, particularly IL-23, on abnormal neurocognitive testing. PMID

  1. Inflammatory Bowel Disease (IBD) and Pregnancy

    MedlinePlus

    ... Inflammatory Bowel Disease? Inflammatory bowel disease (IBD) includes Crohn’s disease (CD) and ulcerative colitis (UC). Symptoms include abdominal ... become pregnant? Women with ulcerative colitis and inactive Crohn’s disease are as likely to become pregnant as women ...

  2. Pelvic Inflammatory Disease (PID) Treatment and Care

    MedlinePlus

    ... Herpes Gonorrhea Hepatitis HIV/AIDS & STDs Human Papillomavirus (HPV) Pelvic Inflammatory Disease ... is pelvic inflammatory disease treated? Several types of antibiotics can cure PID. Antibiotic treatment does not, however, reverse any ...

  3. Immunopathologic effects of scorpion venom on hepato-renal tissues: Involvement of lipid derived inflammatory mediators.

    PubMed

    Lamraoui, Amal; Adi-Bessalem, Sonia; Laraba-Djebari, Fatima

    2015-10-01

    Scorpion venoms are known to cause different inflammatory disorders through complex mechanisms in various tissues. In the study here, the involvement of phospholipase A2 (PLA2) and cyclo-oxygenase (COX)-derived metabolites in hepatic and renal inflammation responses were examined. Mice were envenomed with Androctonus australis hector scorpion venom in the absence or presence of inhibitors that can interfere with lipid inflammatory mediator synthesis, i.e., dexamethasone (PLA2 inhibitor), indomethacin (non-selective COX-1/COX-2 inhibitor), or celecoxib (selective COX-2 inhibitor). The inflammatory response was assessed by evaluating vascular permeability changes, inflammatory cell infiltration, oxidative/nitrosative stress marker levels, and by histologic and functional analyses of the liver and kidney. Results revealed that the venom alone induced an inflammatory response in this tissues marked by increased microvascular permeability and inflammatory cell infiltration, increases in levels of nitric oxide and lipid peroxidation, and decreases in antioxidant defense. Moreover, significant alterations in the histological architecture of these organs were associated with increased serum levels of some metabolic enzymes, as well as urea and uric acid. Pre-treatment of mice with dexamethasone led to significant decreases of the inflammatory disorders in the hepatic parenchyma; celecoxib pre-treatment seemed to be more effective against renal inflammation. Indomethacin pre-treatment only slightly reduced the inflammatory disorders in the tissues. These results suggest that the induced inflammation response in liver was mediated mainly by PLA2 activation, while the renal inflammatory process was mediated by prostaglandin formation by COX-2. These findings provide additional insight toward the understanding of activated pathways and related mechanisms involved in scorpion envenoming syndrome.

  4. Facilitated spinal neuropeptide signaling and upregulated inflammatory mediator expression contribute to post-fracture nociceptive sensitization

    PubMed Central

    Shi, Xiaoyou; Guo, Tian-zhi; Wei, Tzuping; Li, Wen-wu; Clark, David J; Kingery, Wade S

    2015-01-01

    Tibia fracture induces exaggerated substance P (SP) and CGRP signaling and neuropeptide-dependent nociceptive and inflammatory changes in the hindlimbs of rats similar to those seen in complex regional pain syndrome (CRPS). Inflammatory changes in the spinal cord contribute to nociceptive sensitization in a variety of animal pain models. This study tested the hypothesis that fracture induced exaggerated neuropeptide signaling up-regulates spinal inflammatory mediator expression, leading to post-fracture hindlimb nociceptive sensitization. At 4 weeks after performing tibia fracture and casting in rats, we measured hindlimb allodynia, unweighting, warmth, edema, and spinal cord neuropeptide and inflammatory mediator content. The antinociceptive effects of intrathecally injected neuropeptide and inflammatory mediator receptor antagonists were evaluated in fracture rats. Transgenic fracture mice lacking SP or the CGRP RAMP1 receptor were used to determine the effects of neuropeptide signaling on post-fracture pain behavior and spinal inflammatory mediator expression. Hindlimb allodynia, unweighting, warmth, edema, increased spinal SP and CGRP, and increased spinal inflammatory mediator expression (TNF, IL-1, IL-6, CCL2, NGF) were observed at 4 weeks after fracture in rats. Fracture induced increases in spinal inflammatory mediators were not observed in fracture mice lacking SP or the CGRP receptor and these mice had attenuated post-fracture nociceptive sensitization. Intrathecal injection of selective receptor antagonists for SP, CGRP, TNF, IL-1, IL-6, CCL2, or NGF each reduced pain behaviors in the fracture rats. Collectively, these data support the hypothesis that facilitated spinal neuropeptide signaling up-regulates the expression of spinal inflammatory mediators contributing to nociceptive sensitization in a rodent fracture model of CRPS. PMID:25932690

  5. Pyogenic Arthritis, Pyoderma Gangrenosum, Acne, Suppurative Hidradenitis (PA-PASH) Syndrome: An Atypical Presentation of a Rare Syndrome.

    PubMed

    Ursani, Mohammad A; Appleyard, Joan; Whiteru, Onome

    2016-08-17

    BACKGROUND Pyogenic arthritis, pyoderma gangrenosum (PG), acne, and suppurative hidradenitis (PA-PASH) syndrome has been linked to an auto-inflammatory pathway. We report a case that is an atypical presentation of a rare syndrome, which supports literature suggesting that different phenotypes of PG-related syndromes may be a variation of the same pathogenic spectrum. Interestingly, our patient displayed a positive proteinase-3 antibody (PR-3). The clinical relevance of this is unclear. In recent literature, antineutrophil cytoplasmic autoantibodies (ANCA) positivity has been reported in various inflammatory conditions other than ANCA-associated vasculitis (AAV). CASE REPORT A 44-year-old African American male with history of pyogenic arthritis, acne, suppurative hidradenitis, and chronic diarrhea presented for evaluation of painful ulcers located on the bilateral lower extremities, bilateral proximal interphalangeal joints, buttocks, and scrotum, and chronic diarrhea. Infectious etiologies for the ulcers were ruled out. Biopsy of an ulcer revealed PG. Colonoscopy revealed inflammation and ulceration with biopsy consistent with ulcerative colitis (UC). After treatment with prednisone, the ulcers healed within 4 weeks, and the chronic diarrhea resolved. CONCLUSIONS Our patient displayed a variation of PA-PASH syndrome and UC. Previously reported cases of similar phenotypes of PG-related syndromes have not presented in this fashion. Furthermore, the literature does not report cases of PG-related syndromes with an elevation in PR-3 antibody. Elevation in PR-3 has been reported in various inflammatory disorders aside from AAV. The relevance of this is currently unclear. It may be possible that the milieus of these various auto-inflammatory disorders may share pathogenic commonalities.

  6. Pyogenic Arthritis, Pyoderma Gangrenosum, Acne, Suppurative Hidradenitis (PA-PASH) Syndrome: An Atypical Presentation of a Rare Syndrome.

    PubMed

    Ursani, Mohammad A; Appleyard, Joan; Whiteru, Onome

    2016-01-01

    BACKGROUND Pyogenic arthritis, pyoderma gangrenosum (PG), acne, and suppurative hidradenitis (PA-PASH) syndrome has been linked to an auto-inflammatory pathway. We report a case that is an atypical presentation of a rare syndrome, which supports literature suggesting that different phenotypes of PG-related syndromes may be a variation of the same pathogenic spectrum. Interestingly, our patient displayed a positive proteinase-3 antibody (PR-3). The clinical relevance of this is unclear. In recent literature, antineutrophil cytoplasmic autoantibodies (ANCA) positivity has been reported in various inflammatory conditions other than ANCA-associated vasculitis (AAV). CASE REPORT A 44-year-old African American male with history of pyogenic arthritis, acne, suppurative hidradenitis, and chronic diarrhea presented for evaluation of painful ulcers located on the bilateral lower extremities, bilateral proximal interphalangeal joints, buttocks, and scrotum, and chronic diarrhea. Infectious etiologies for the ulcers were ruled out. Biopsy of an ulcer revealed PG. Colonoscopy revealed inflammation and ulceration with biopsy consistent with ulcerative colitis (UC). After treatment with prednisone, the ulcers healed within 4 weeks, and the chronic diarrhea resolved. CONCLUSIONS Our patient displayed a variation of PA-PASH syndrome and UC. Previously reported cases of similar phenotypes of PG-related syndromes have not presented in this fashion. Furthermore, the literature does not report cases of PG-related syndromes with an elevation in PR-3 antibody. Elevation in PR-3 has been reported in various inflammatory disorders aside from AAV. The relevance of this is currently unclear. It may be possible that the milieus of these various auto-inflammatory disorders may share pathogenic commonalities. PMID:27530224

  7. Cushing's syndrome.

    PubMed

    Howlett, T A; Rees, L H; Besser, G M

    1985-11-01

    Cushing's syndrome remains one of the most challenging problems in clinical endocrinology. Cushing's disease is caused in the majority of cases by basophil pituitary microadenomas which may be successfully treated by trans-sphenoidal hypophysectomy. Treatment with metyrapone or o,p'-DDD can always induce a clinical remission but not a cure, and neurotransmitter therapy may be effective in a minority of cases. Pituitary irradiation cures about half of cases in the long-term and may be used for surgical failures. Tumours producing ectopic ACTH are frequently benign, small and occult and may produce a syndrome clinically indistinguishable from Cushing's disease. Biochemical investigations cannot absolutely distinguish pituitary from ectopic sources of ACTH and therefore body CT scanning and percatheter venous sampling are essential diagnostic investigations. Tumour localization may result in resection and complete cure, although even small tumours may have a malignant potential. Adrenal tumours are readily diagnosed by plasma ACTH measurement and adrenal CT scanning. Adrenal adenomas are cured by adrenalectomy. Carcinomas may be treated by a combination of adrenalectomy, radiotherapy and o,p'-DDD, but long-term prognosis is poor.

  8. Cutaneous and ocular manifestations of neurocutaneous syndromes.

    PubMed

    Chernoff, Karen A; Schaffer, Julie V

    2016-01-01

    Neurocutaneous syndromes are a heterogeneous group of congenital and hereditary disorders with manifestations in the skin and the nervous system, usually together with ocular features that represent diagnostic clues and potential sources of morbidity. Dermatologists and ophthalmologists often need to work together in identifying and managing patients with these conditions; herein, we focus on classic and under-recognized neurocutaneous syndromes. We begin with autosomal dominant genodermatoses characterized by hamartomas and tumors in the skin, eyes, and central nervous system: neurofibromatosis type 1, tuberous sclerosis complex, and PTEN hamartoma-tumor syndrome. This is followed by a discussion of two mosaic disorders, Sturge-Weber syndrome and neurocutaneous melanocytosis. In addition to providing an update on clinical presentations and evaluation of patients with these conditions, we review recent insights into their pathogenesis, drawing attention to relationships among the diseases on a molecular level and implications regarding treatment. We also highlight the major features of other neurocutaneous syndromes that have ocular findings plus pigmentary, vascular, hyperkeratotic, adnexal, connective tissue, photosensitive, and inflammatory manifestations in the skin. PMID:26903185

  9. NASH is an Inflammatory Disorder: Pathogenic, Prognostic and Therapeutic Implications

    PubMed Central

    van Rooyen, Derrick; Gan, Lay; Chitturi, Shivrakumar

    2012-01-01

    While non-alcoholic fatty liver disease (NAFLD) is highly prevalent (15% to 45%) in modern societies, only 10% to 25% of cases develop hepatic fibrosis leading to cirrhosis, end-stage liver disease or hepatocellular carcinoma. Apart from pre-existing fibrosis, the strongest predictor of fibrotic progression in NAFLD is steatohepatitis or non-alcoholic steatohepatitis (NASH). The critical features other than steatosis are hepatocellular degeneration (ballooning, Mallory hyaline) and mixed inflammatory cell infiltration. While much is understood about the relationship of steatosis to metabolic factors (over-nutrition, insulin resistance, hyperglycemia, metabolic syndrome, hypoadiponectinemia), less is known about inflammatory recruitment, despite its importance for the perpetuation of liver injury and fibrogenesis. In this review, we present evidence that liver inflammation has prognostic significance in NAFLD. We then consider the origins and components of liver inflammation in NASH. Hepatocytes injured by toxic lipid molecules (lipotoxicity) play a central role in the recruitment of innate immunity involving Toll-like receptors (TLRs), Kupffer cells (KCs), lymphocytes and neutrophils and possibly inflammasome. The key pro-inflammatory signaling pathways in NASH are nuclear factor-kappa B (NF-κB) and c-Jun N-terminal kinase (JNK). The downstream effectors include adhesion molecules, chemokines, cytokines and the activation of cell death pathways leading to apoptosis. The upstream activators of NF-κB and JNK are more contentious and may depend on the experimental model used. TLRs are strong contenders. It remains possible that inflammation in NASH originates outside the liver and in the gut microbiota that prime KC/TLR responses, inflamed adipose tissue and circulating inflammatory cells. We briefly review these mechanistic considerations and project their implications for the effective treatment of NASH. PMID:22570745

  10. 9 CFR 381.86 - Inflammatory processes.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Inflammatory processes. 381.86 Section... Carcasses and Parts § 381.86 Inflammatory processes. Any organ or other part of a carcass which is affected by an inflammatory process shall be condemned and, if there is evidence of general...

  11. Computed tomography in the evaluation of Brown syndrome of the superior oblique tendon sheath

    SciTech Connect

    Mafee, M.F.; Folk, E.R.; Langer, B.G.; Miller, M.T.; Lagouros, P.; Mittleman, D.

    1985-03-01

    Computed tomographic (CT) findings in 4 patients with superior oblique tendon sheath syndrome (congenital or acquired Brown syndrome) are described. When the inferior oblique muscle moves the eye upward, the superior oblique muscle normally relaxes, while its tendon lengthens and slides freely through the trochlea. In Brown syndrome this process is somehow restricted, which is most apparent during attempts at elevation when the eye is adducted, resulting in an apparent inferior oblique palsy (pseudopalsy). CT is a valuable tool in understanding the pathophysiology and management of acquired Brown syndrome, showing thickening and inflammatory changes of the reflected portion of the superior oblique tendon.

  12. Diet and Inflammatory Bowel Disease.

    PubMed

    Knight-Sepulveda, Karina; Kais, Susan; Santaolalla, Rebeca; Abreu, Maria T

    2015-08-01

    Patients with inflammatory bowel disease (IBD) are increasingly becoming interested in nonpharmacologic approaches to managing their disease. One of the most frequently asked questions of IBD patients is what they should eat. The role of diet has become very important in the prevention and treatment of IBD. Although there is a general lack of rigorous scientific evidence that demonstrates which diet is best for certain patients, several diets-such as the low-fermentable oligosaccharide, disaccharide, monosaccharide, and polyol diet; the specific carbohydrate diet; the anti-inflammatory diet; and the Paleolithic diet-have become popular. This article discusses the diets commonly recommended to IBD patients and reviews the supporting data. PMID:27118948

  13. Diet and Inflammatory Bowel Disease

    PubMed Central

    Knight-Sepulveda, Karina; Kais, Susan; Santaolalla, Rebeca

    2015-01-01

    Patients with inflammatory bowel disease (IBD) are increasingly becoming interested in nonpharmacologic approaches to managing their disease. One of the most frequently asked questions of IBD patients is what they should eat. The role of diet has become very important in the prevention and treatment of IBD. Although there is a general lack of rigorous scientific evidence that demonstrates which diet is best for certain patients, several diets—such as the low-fermentable oligosaccharide, disaccharide, monosaccharide, and polyol diet; the specific carbohydrate diet; the anti-inflammatory diet; and the Paleolithic diet—have become popular. This article discusses the diets commonly recommended to IBD patients and reviews the supporting data. PMID:27118948

  14. Costs in inflammatory bowel diseases

    PubMed Central

    Witczak, Izabela

    2016-01-01

    Variables influencing total direct medical costs in inflammatory bowel diseases include country, diagnosis (generally, patients with Crohn's disease generated higher costs compared with patients with ulcerative colitis), and year since diagnosis. In all studies the mean costs were higher than the median costs, which indicates that a relatively small group of the most severely ill patients significantly affect the total cost of treatment of these diseases. A major component of direct medical costs was attributed to hospitalisation, ranging from 49% to 80% of the total. The costs of surgery constituted 40–61% of inpatient costs. Indirect costs in inflammatory bowel diseases, unappreciated and often underestimated (considered by few authors and as a loss of work), are in fact important and may even exceed direct medical costs. PMID:27110304

  15. Inflammatory breast cancer: an overview.

    PubMed

    van Uden, D J P; van Laarhoven, H W M; Westenberg, A H; de Wilt, J H W; Blanken-Peeters, C F J M

    2015-02-01

    Inflammatory breast cancer (IBC) is the most aggressive entity of breast cancer. Management involves coordination of multidisciplinary management and usually includes neoadjuvant chemotherapy, ablative surgery if a tumor-free resection margin is expected and locoregional radiotherapy. This multimodal therapeutic approach has significantly improved patient survival. However, the median overall survival among women with IBC is still poor. By elucidating the biologic characteristics of IBC, new treatment options may become available. We performed a comprehensive review of the English-language literature on IBC through computerized literature searches. The objective of the current review is to present an overview of the literature related to the biology, imaging and multidisciplinary treatment of inflammatory breast cancer.

  16. Consensus statement on surgical pathology of the aorta from the Society for Cardiovascular Pathology and the Association for European Cardiovascular Pathology: I. Inflammatory diseases.

    PubMed

    Stone, James R; Bruneval, Patrick; Angelini, Annalisa; Bartoloni, Giovanni; Basso, Cristina; Batoroeva, Lubov; Buja, L Maximilian; Butany, Jagdish; d'Amati, Giulia; Fallon, John T; Gittenberger-de Groot, Adriana C; Gouveia, Rosa H; Halushka, Marc K; Kelly, Karen L; Kholova, Ivana; Leone, Ornella; Litovsky, Silvio H; Maleszewski, Joseph J; Miller, Dylan V; Mitchell, Richard N; Preston, Stephen D; Pucci, Angela; Radio, Stanley J; Rodriguez, E Rene; Sheppard, Mary N; Suvarna, S Kim; Tan, Carmela D; Thiene, Gaetano; van der Wal, Allard C; Veinot, John P

    2015-01-01

    Inflammatory diseases of the aorta include routine atherosclerosis, aortitis, periaortitis, and atherosclerosis with excessive inflammatory responses, such as inflammatory atherosclerotic aneurysms. The nomenclature and histologic features of these disorders are reviewed and discussed. In addition, diagnostic criteria are provided to distinguish between these disorders in surgical pathology specimens. An initial classification scheme is provided for aortitis and periaortitis based on the pattern of the inflammatory infiltrate: granulomatous/giant cell pattern, lymphoplasmacytic pattern, mixed inflammatory pattern, and the suppurative pattern. These inflammatory patterns are discussed in relation to specific systemic diseases including giant cell arteritis, Takayasu arteritis, granulomatosis with polyangiitis (Wegener's), rheumatoid arthritis, sarcoidosis, ankylosing spondylitis, Cogan syndrome, Behçet's disease, relapsing polychondritis, syphilitic aortitis, and bacterial and fungal infections.

  17. Lactobacillus rhamnosus blocks inflammatory signaling in vivo via reactive oxygen species generation.

    PubMed

    Lin, Patricia W; Myers, Loren E S; Ray, Laurie; Song, Shuh-Chyung; Nasr, Tala R; Berardinelli, Andrew J; Kundu, Kousik; Murthy, Niren; Hansen, Jason M; Neish, Andrew S

    2009-10-15

    Uncontrolled inflammatory responses in the immature gut may play a role in the pathogenesis of many intestinal inflammatory syndromes that present in newborns or children, such as necrotizing enterocolitis (NEC), idiopathic inflammatory bowel diseases (IBD), or infectious enteritis. Consistent with previous reports that murine intestinal function matures over the first 3 weeks of life, we show that inflammatory signaling in the neonatal mouse gut increases during postnatal maturation, with peak responses occurring at 2-3 weeks. Probiotic bacteria can block inflammatory responses in cultured epithelia by inducing the generation of reactive oxygen species (ROS), which inhibit NF-kappaB activation through oxidative inactivation of the key regulatory enzyme Ubc12. We now report for the first time that the probiotic Lactobacillus rhamnosus GG (LGG) can induce ROS generation in intestinal epithelia in vitro and in vivo. Intestines from immature mice gavage fed LGG exhibited increased GSH oxidation and cullin-1 deneddylation, reflecting local ROS generation and its resultant Ubc12 inactivation, respectively. Furthermore, prefeeding LGG prevented TNF-alpha-induced intestinal NF-kappaB activation. These studies indicate that LGG can reduce inflammatory signaling in immature intestines by inducing local ROS generation and may be a mechanism by which probiotic bacteria can prevent NEC in premature infants or reduce the severity of IBD in children.

  18. Impact of physical activity on inflammation: effects on cardiovascular disease risk and other inflammatory conditions

    PubMed Central

    Cicero, Arrigo

    2012-01-01

    Since the 19th century, many studies have enlightened the role of inflammation in atherosclerosis, changing our perception of “vessel plaque due to oxidized lipoproteins”, similar to a “rusted pipe”, towards a disease with involvement of many cell types and cytokines with more complex mechanisms. Although “physical activity” and “physical exercise” are two terms with some differences in meaning, compared to sedentary lifestyle, active people have lower cardiovascular risk and lower inflammatory markers. Activities of skeletal muscle reveal “myokines” which have roles in both the immune system and adipose tissue metabolism. In vitro and ex-vivo studies have shown beneficial effects of exercise on inflammation markers. Meanwhile in clinical studies, some conflicting results suggested that type of activity, exercise duration, body composition, gender, race and age may modulate anti-inflammatory effects of physical exercise. Medical data on patients with inflammatory diseases have shown beneficial effects of exercise on disease activity scores, patient well-being and inflammatory markers. Although the most beneficial type of activity and the most relevant patient group for anti-inflammatory benefits are still not clear, studies in elderly and adult people generally support anti-inflammatory effects of physical activity and moderate exercise could be advised to patients with cardiovascular risk such as patients with metabolic syndrome. PMID:23185187

  19. Inflammatory diseases modelling in zebrafish

    PubMed Central

    Morales Fénero, Camila Idelí; Colombo Flores, Alicia Angelina; Câmara, Niels Olsen Saraiva

    2016-01-01

    The ingest of diets with high content of fats and carbohydrates, low or no physical exercise and a stressful routine are part of the everyday lifestyle of most people in the western world. These conditions are triggers for different diseases with complex interactions between the host genetics, the metabolism, the immune system and the microbiota, including inflammatory bowel diseases (IBD), obesity and diabetes. The incidence of these disorders is growing worldwide; therefore, new strategies for its study are needed. Nowadays, the majority of researches are in use of murine models for understand the genetics, physiopathology and interaction between cells and signaling pathways to find therapeutic solutions to these diseases. The zebrafish, a little tropical water fish, shares 70% of our genes and conserves anatomic and physiological characteristics, as well as metabolical pathways, with mammals, and is rising as a new complementary model for the study of metabolic and inflammatory diseases. Its high fecundity, fast development, transparency, versatility and low cost of maintenance makes the zebrafish an interesting option for new researches. In this review, we offer a discussion of the existing genetic and induced zebrafish models of two important Western diseases that have a strong inflammatory component, the IBD and the obesity. PMID:26929916

  20. [Inflammatory Bowel Disease Competence Network].

    PubMed

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

    2016-04-01

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

  1. IL-1 Blockade in Autoinflammatory Syndromes1

    PubMed Central

    Jesus, Adriana A.; Goldbach-Mansky, Raphaela

    2014-01-01

    Monogenic autoinflammatory syndromes present with excessive systemic inflammation including fever, rashes, arthritis, and organ-specific inflammation and are caused by defects in single genes encoding proteins that regulate innate inflammatory pathways. Pathogenic variants in two interleukin-1 (IL-1)–regulating genes, NLRP3 and IL1RN, cause two severe and early-onset autoinflammatory syndromes, CAPS (cryopyrin associated periodic syndromes) and DIRA (deficiency of IL-1 receptor antagonist). The discovery of the mutations that cause CAPS and DIRA led to clinical and basic research that uncovered the key role of IL-1 in an extended spectrum of immune dysregulatory conditions. NLRP3 encodes cryopyrin, an intracellular “molecular sensor” that forms a multimolecular platform, the NLRP3 inflammasome, which links “danger recognition” to the activation of the proinflammatory cytokine IL-1β. The success and safety profile of drugs targeting IL-1 in the treatment of CAPS and DIRA have encouraged their wider use in other autoinflammatory syndromes including the classic hereditary periodic fever syndromes (familial Mediterranean fever, TNF receptor–associated periodic syndrome, and hyperimmunoglobulinemia D with periodic fever syndrome) and additional immune dysregulatory conditions that are not genetically well defined, including Still’s, Behcet’s, and Schnitzler diseases. The fact that the accumulation of metabolic substrates such as monosodium urate, ceramide, cholesterol, and glucose can trigger the NLRP3 inflammasome connects metabolic stress to IL-1β-mediated inflammation and provides a rationale for therapeutically targeting IL-1 in prevalent diseases such as gout, diabetes mellitus, and coronary artery disease. PMID:24422572

  2. Metabolic Syndrome: Polycystic Ovary Syndrome.

    PubMed

    Mortada, Rami; Williams, Tracy

    2015-08-01

    Polycystic ovary syndrome (PCOS) is a heterogeneous condition characterized by androgen excess, ovulatory dysfunction, and polycystic ovaries. It is the most common endocrinopathy among women of reproductive age, affecting between 6.5% and 8% of women, and is the most common cause of infertility. Insulin resistance is almost always present in women with PCOS, regardless of weight, and they often develop diabetes and metabolic syndrome. The Rotterdam criteria are widely used for diagnosis. These criteria require that patients have at least two of the following conditions: hyperandrogenism, ovulatory dysfunction, and polycystic ovaries. The diagnosis of PCOS also requires exclusion of other potential etiologies of hyperandrogenism and ovulatory dysfunction. The approach to PCOS management differs according to the presenting symptoms and treatment goals, particularly the patient's desire for pregnancy. Weight loss through dietary modifications and exercise is recommended for patients with PCOS who are overweight. Oral contraceptives are the first-line treatment for regulating menstrual cycles and reducing manifestations of hyperandrogenism, such as acne and hirsutism. Clomiphene is the first-line drug for management of anovulatory infertility. Metformin is recommended for metabolic abnormalities such as prediabetes, and a statin should be prescribed for cardioprotection if the patient meets standard criteria for statin therapy.

  3. The metabolic syndrome as a concept of adipose tissue disease.

    PubMed

    Oda, Eiji

    2008-07-01

    The metabolic syndrome is a constellation of interrelated metabolic risk factors that appear to directly promote the development of diabetes and cardiovascular disease. However, in 2005, the American Diabetes Association and the European Association for the Study of Diabetes jointly stated that no existing definition of the metabolic syndrome meets the criteria of a syndrome, and there have been endless debates on the pros and cons of using the concept of this syndrome. The controversy may stem from confusion between the syndrome and obesity. Obesity is an epidemic, essentially contagious disease caused by an environment of excess nutritional energy and reinforced by deeply rooted social norms. The epidemic of obesity should be prevented or controlled by social and political means, similar to the approaches now being taken to combat global warming. The diagnosis of metabolic syndrome is useless for this public purpose. The purpose of establishing criteria for diagnosing metabolic syndrome is to find individuals who are at increased risk of diabetes and cardiovascular disease and who require specific therapy including diet and exercise. The syndrome may be an adipose tissue disease different from obesity; in that case, it would be characterized by inflammation clinically detected through systemic inflammatory markers such as high-sensitivity C-reactive protein and insulin resistance reflecting histological changes in adipose tissue. However, many problems in defining the optimal diagnostic criteria remain unresolved.

  4. Syndromes with supernumerary teeth.

    PubMed

    Lubinsky, Mark; Kantaputra, Piranit Nik

    2016-10-01

    While most supernumerary teeth are idiopathic, they can be associated with a number of Mendelian syndromes. However, this can also be a coincidental finding, since supernumerary teeth occur in 6% or more of the normal population. To better define this relationship, we analyzed the evidence for specific associations. We excluded conditions with a single affected patient reported, supernumerary teeth adjacent to clefts or other forms of alveolar disruption (as secondary rather than primary findings), and natal teeth, which can involve premature eruption of a normal tooth. Since, the cause of supernumerary teeth shows considerable heterogeneity, certain findings are less likely to be coincidental, such as five or more supernumerary teeth in a single patient, or locations outside of the premaxilla. We found only eight genetic syndromes with strong evidence for an association: cleidocranial dysplasia; familial adenomatous polyposis; trichorhinophalangeal syndrome, type I; Rubinstein-Taybi syndrome; Nance-Horan syndrome; Opitz BBB/G syndrome; oculofaciocardiodental syndrome; and autosomal dominant Robinow syndrome. There is also suggestive evidence of an association with two uncommon disorders, Kreiborg-Pakistani syndrome (craniosynostosis and dental anomalies), and insulin-resistant diabetes mellitus with acanthosisnigricans. An association of a Mendelian disorder with a low frequency manifestation of supernumerary teeth is difficult to exclude without large numbers, but several commonly cited syndromes lacked evidence for clear association, including Hallermann-Streiff syndrome, Fabry disease, Ehlers-Danlos syndrome, Apert and Crouzon syndromes, Zimmermann-Laband syndrome, and Ellis-van Creveld syndrome. © 2016 Wiley Periodicals, Inc.

  5. Syndromes with supernumerary teeth.

    PubMed

    Lubinsky, Mark; Kantaputra, Piranit Nik

    2016-10-01

    While most supernumerary teeth are idiopathic, they can be associated with a number of Mendelian syndromes. However, this can also be a coincidental finding, since supernumerary teeth occur in 6% or more of the normal population. To better define this relationship, we analyzed the evidence for specific associations. We excluded conditions with a single affected patient reported, supernumerary teeth adjacent to clefts or other forms of alveolar disruption (as secondary rather than primary findings), and natal teeth, which can involve premature eruption of a normal tooth. Since, the cause of supernumerary teeth shows considerable heterogeneity, certain findings are less likely to be coincidental, such as five or more supernumerary teeth in a single patient, or locations outside of the premaxilla. We found only eight genetic syndromes with strong evidence for an association: cleidocranial dysplasia; familial adenomatous polyposis; trichorhinophalangeal syndrome, type I; Rubinstein-Taybi syndrome; Nance-Horan syndrome; Opitz BBB/G syndrome; oculofaciocardiodental syndrome; and autosomal dominant Robinow syndrome. There is also suggestive evidence of an association with two uncommon disorders, Kreiborg-Pakistani syndrome (craniosynostosis and dental anomalies), and insulin-resistant diabetes mellitus with acanthosisnigricans. An association of a Mendelian disorder with a low frequency manifestation of supernumerary teeth is difficult to exclude without large numbers, but several commonly cited syndromes lacked evidence for clear association, including Hallermann-Streiff syndrome, Fabry disease, Ehlers-Danlos syndrome, Apert and Crouzon syndromes, Zimmermann-Laband syndrome, and Ellis-van Creveld syndrome. © 2016 Wiley Periodicals, Inc. PMID:27250821

  6. [Hepatopulmonary syndrome].

    PubMed

    Thévenot, Thierry; Weil, Delphine; Garioud, Armand; Lison, Hortensia; Cadranel, Jean-François; Degano, Bruno

    2016-05-01

    Hepatopulmonary syndrome (HPS) is defined by the association of portal hypertension, increased alveolar-arterial oxygen gradient and intrapulmonary vascular dilations. Pathophysiological mechanisms of hypoxemia are characterized by ventilation-perfusion mismatch, oxygen diffusion limitation between alveolus and the centre of the dilated capillary, and right-to-left shunting. An excess of vasodilator molecules (like nitric monoxide) and proangiogenic factors (like VEGF) play an important role in the occurrence of HPS. Symptoms of HPS are not specific and dominated by a progressive dyspnea in upright position. Pulse oximetry is a simple non-invasive screening test but only detect the most severe forms of HPS. Medical treatment is disappointing and only liver transplantation may lead to resolution of HPS. Survival following liver transplantation is promising when hypoxemia is not severely decreased. PMID:27021476

  7. Noonan syndrome.

    PubMed

    Turner, Anne M

    2014-10-01

    Noonan syndrome is a common autosomal dominant condition, readily recognisable in childhood. It is characterised by a pattern of typical facial dysmorphism and malformations including congenital cardiac defects, short stature, abnormal chest shape, broad or webbed neck, and a variable learning disability. Mildly affected adults may not be diagnosed until the birth of a more obviously affected child. The phenotype is highly variable. Important progress in understanding the molecular basis of this and other related conditions was made in 2001 when germline mutations in the PTPN11 gene were found to account for ∼50% of cases. Since then, mutations in additional genes in the rat sarcoma (RAS) pathway have been identified in a proportion of the remainder. Molecular confirmation of diagnosis is now possible for many families and has become increasingly important in guiding management. Increased awareness by paediatricians will lead to earlier diagnosis, and provide patients and their families with accurate genetic counselling, including options when planning pregnancy.

  8. Extrapyramidal syndrome

    PubMed Central

    Panda, Akhila Kumar; Bala, Kiran; Bhirud, Lomesh

    2014-01-01

    Organophosphate (OP) poisoning is a common occurrence in the rural areas of developing countries like India. Acute cholinergic crisis is one of the important causes of mortality related to OP poisoning. Delayed peripheral neuropathy, extrapyramidal syndromes and neuropsychiatric manifestations are the major consequences of secondary neuronal damage. This case illustrates a 14-year-old girl who ingested 50 mL of OP pesticide and developed extrapyramidal symptoms in the form of parkinsonism and hand dystonia in spite of immediate medical attention. MRI of the brain with T2, fluid attenuated inversion recovery and diffusion-weighted sequences revealed bilateral symmetrical basal ganglia hyperintensities. Further follow-up revealed a significant clinical improvement with marked resolutions of the brain lesions. The reversible extrapyramidal symptoms with disappearance of neuroimaging findings without neuropathy or neuropsychiatric manifestations are unusual in OP poisoning. PMID:24398867

  9. Rett Syndrome

    PubMed Central

    Smeets, E.E.J.; Pelc, K.; Dan, B.

    2012-01-01

    Rett syndrome is one of the most common causes of complex disability in girls. It is characterized by early neurological regression that severely affects motor, cognitive and communication skills, by autonomic dysfunction and often a seizure disorder. It is a monogenic X-linked dominant neurodevelopmental disorder related to mutation in MECP2, which encodes the methyl-CpG-binding protein MeCP2. There are several mouse models either based on conditional knocking out of the Mecp2 gene or on a truncating mutation. We discuss the clinical aspects with special emphasis on the behavioral phenotype and we review current perspectives in clinical management alongside with perspectives in altering gene expression. PMID:22670134

  10. Inflammatory therapeutic targets in coronary atherosclerosis-from molecular biology to clinical application.

    PubMed

    Linden, Fabian; Domschke, Gabriele; Erbel, Christian; Akhavanpoor, Mohammadreza; Katus, Hugo A; Gleissner, Christian A

    2014-01-01

    Atherosclerosis is the leading cause of death worldwide. Over the past two decades, it has been clearly recognized that atherosclerosis is an inflammatory disease of the arterial wall. Accumulating data from animal experiments have supported this hypothesis, however, clinical applications making use of this knowledge remain scarce. In spite of optimal interventional and medical therapy, the risk for recurrent myocardial infarction remains by about 20% over 3 years after acute coronary syndromes, novel therapies to prevent atherogenesis or treat atherosclerosis are urgently needed. This review summarizes selected potential molecular inflammatory targets that may be of clinical relevance. We also review recent and ongoing clinical trails that target inflammatory processes aiming at preventing adverse cardiovascular events. Overall, it seems surprising that translation of basic science into clinical practice has not been a great success. In conclusion, we propose to focus on specific efforts that promote translational science in order to improve outcome and prognosis of patients suffering from atherosclerosis.

  11. Inflammatory therapeutic targets in coronary atherosclerosis—from molecular biology to clinical application

    PubMed Central

    Linden, Fabian; Domschke, Gabriele; Erbel, Christian; Akhavanpoor, Mohammadreza; Katus, Hugo A.; Gleissner, Christian A.

    2014-01-01

    Atherosclerosis is the leading cause of death worldwide. Over the past two decades, it has been clearly recognized that atherosclerosis is an inflammatory disease of the arterial wall. Accumulating data from animal experiments have supported this hypothesis, however, clinical applications making use of this knowledge remain scarce. In spite of optimal interventional and medical therapy, the risk for recurrent myocardial infarction remains by about 20% over 3 years after acute coronary syndromes, novel therapies to prevent atherogenesis or treat atherosclerosis are urgently needed. This review summarizes selected potential molecular inflammatory targets that may be of clinical relevance. We also review recent and ongoing clinical trails that target inflammatory processes aiming at preventing adverse cardiovascular events. Overall, it seems surprising that translation of basic science into clinical practice has not been a great success. In conclusion, we propose to focus on specific efforts that promote translational science in order to improve outcome and prognosis of patients suffering from atherosclerosis. PMID:25484870

  12. Phenomics in Autoimmune and Inflammatory Diseases

    ClinicalTrials.gov

    2016-04-18

    Healthy Volunteer; Rheumatoid Arthritis; Ankylosing Spondylitis; Systemic Lupus Erythematosus/Antiphospholipid Syndrome; FMF; Cryopyrin-Associated Periodic Syndromes /TNF-receptor Associated Periodic Syndrome; Vasculitis; Uveitis; Myositis; Crohn's Disease; Ulcerative Rectocolitis; Type 1 Diabetes; Unclassified IAD Knee and/or Hip Arthritis, Muscular Dystrophy

  13. Postperfusion lung syndrome: Respiratory mechanics, respiratory indices and biomarkers

    PubMed Central

    Yuan, Shi-Min

    2015-01-01

    Postperfusion lung syndrome is rare but lethal. Secondary inflammatory response was the popularly accepted theory for the underlying etiology. Respiratory index (RI) and arterial oxygen tension/fractional inspired oxygen can be reliable indices for the diagnosis of this syndrome as X-ray appearance is always insignificant at the early stage of the onset. Evaluations of extravascular lung water content and pulmonary compliance are also helpful in the definite diagnosis. Multiorgan failure and triple acid-base disturbances that might develop secondary to postperfusion lung syndrome are responsible for the poor prognosis and increased mortality rather than postperfusion lung syndrome itself. Mechanical ventilation with low tidal volume (TV) and proper positive end-expiratory pressure can be an effective treatment strategy. Use of ulinastatin and propofol may benefit the patients through different mechanisms. PMID:26229556

  14. Erythema nodosum leprosum mimicking Sweet's syndrome: an uncommon presentation.

    PubMed

    Mahajan, Vikram K; Abhinav, C; Mehta, Karaninder S; Chauhan, Pushpinder S

    2014-12-01

    Erythema nodosum leprosum (ENL) lesions may uncommonly develop ulceration, necrosis, pustulation or bullae. This 60 year-old female was hospitalised with previously undiagnosed multibacillary (BL) leprosy and Sweet's syndrome-like ENL, a presentation that is rarely reported. In addition to skin lesions simulating Sweet's syndrome, she had anaemia, elevated ESR, and a peripheral leucocytosis with neutrophilia, the laboratory features of Sweet's syndrome. The final diagnosis was made from chronic iridocyclitis, presence of lepra bacilli in slit-skin smears, and histology. The pathogenesis of Sweet's-like ENL remains conjectural. In Sweet's syndrome a complex interplay of various cytokines leading to an abundance of pro- inflammatory cytokines in the target tissues has been postulated to initiate an abnormal tissue response to certain antigens; such findings may eventually explain these uncommon lepra reactions as well. PMID:25675656

  15. Visceral adiposity syndrome.

    PubMed

    Lopes, Heno F; Corrêa-Giannella, Maria Lúcia; Consolim-Colombo, Fernanda M; Egan, Brent M

    2016-01-01

    The association of anthropometric (waist circumference) and hemodynamic (blood pressure) changes with abnormalities in glucose and lipid metabolism has been motivation for a lot of discussions in the last 30 years. Nowadays, blood pressure, body mass index/abdominal circumference, glycemia, triglyceridemia, and HDL-cholesterol concentrations are considered in the definition of Metabolic syndrome, referred as Visceral adiposity syndrome (VAS) in the present review. However, more than 250 years ago an association between visceral and mediastinal obesity with hypertension, gout, and obstructive apnea had already been recognized. Expansion of visceral adipose tissue secondary to chronic over-consumption of calories stimulates the recruitment of macrophages, which assume an inflammatory phenotype and produce cytokines that directly interfere with insulin signaling, resulting in insulin resistance. In turn, insulin resistance (IR) manifests itself in various tissues, contributing to the overall phenotype of VAS. For example, in white adipose tissue, IR results in lipolysis, increased free fatty acids release and worsening of inflammation, since fatty acids can bind to Toll-like receptors. In the liver, IR results in increased hepatic glucose production, contributing to hyperglycemia; in the vascular endothelium and kidney, IR results in vasoconstriction, sodium retention and, consequently, arterial hypertension. Other players have been recognized in the development of VAS, such as genetic predisposition, epigenetic factors associated with exposure to an unfavourable intrauterine environment and the gut microbiota. More recently, experimental and clinical studies have shown the autonomic nervous system participates in modulating visceral adipose tissue. The sympathetic nervous system is related to adipose tissue function and differentiation through beta1, beta2, beta3, alpha1, and alpha2 adrenergic receptors. The relation is bidirectional: sympathetic denervation of

  16. Overview of inflammatory bowel disease.

    PubMed

    Myer, S A

    1984-03-01

    Ulcerative colitis and Crohn's disease have been on the increase in terms of incidence, prevalence, and virulence. The young adult population is affected most frequently and most severely. The cause of inflammatory bowel disease is unknown, but many misconceptions exist about its etiology. Nurses need to be familiar with the similarities and differences between the two illnesses, the treatment, and the prognosis in order to be effective care givers. Good health care can make a significant contribution to the quality of life the patient subsequently has. PMID:6560534

  17. [Inflammatory bowel disease and pregnancy].

    PubMed

    Parfenov, A I

    2012-01-01

    Inflammatory bowel disease (IBD) in pregnant women in their characteristics do not differ from general population, unless they had operations on the pelvic organs. Women with a first pregnancy, regardless of the activity of IBD have an increased risk of adverse pregnancy and high risk births. Most treatment methods are compatible with pregnancy and breastfeeding. Women affected by IBD should discuss their plans for pregnancy with the doctor first in order to know the possible dangers. Every patient in the IBD during pregnancy must be observed by a gastroenterologist, accoucheur and pediatrician to ensure peace of mother and child.

  18. The evolution of inflammatory mediators

    PubMed Central

    Rowley, Andrew F.

    1996-01-01

    Invertebrates do not display the level of sophistication in immune reactivity characteristic of mammals and other ‘higher’ vertebrates. Their great number and diversity of forms, however, reflect their evolutionary success and hence they must have effective mechanisms of defence to deal with parasites and pathogens and altered self tissues. Inflammation appears to be an important first line defence in all invertebrates and vertebrates. This brief review deals with the inflammatory responses of invertebrates and fish concentrating on the cell types involved and the mediators of inflammation, in particular, eicosanoids, cytokines and adhesion molecules. PMID:18475690

  19. PPARγ in Inflammatory Bowel Disease

    PubMed Central

    Annese, Vito; Rogai, Francesca; Settesoldi, Alessia; Bagnoli, Siro

    2012-01-01

    Peroxisome proliferator-activated receptor gamma (PPARγ) is member of a family of nuclear receptors that interacts with nuclear proteins acting as coactivators and corepressors. The colon is a major tissue which expresses PPARγ in epithelial cells and, to a lesser degree, in macrophages and lymphocytes and plays a role in the regulation of intestinal inflammation. Indeed, both natural and synthetic PPARγ ligands have beneficial effects in different models of experimental colitis, with possible implication in the therapy of inflammatory bowel disease (IBD). This paper will specifically focus on potential role of PPARγ in the predisposition and physiopathology of IBD and will analyze its possible role in medical therapy. PMID:22997506

  20. Inflammatory Mechanisms in Hidradenitis Suppurativa.

    PubMed

    Kelly, G; Prens, Errol P

    2016-01-01

    Hidradenitis suppurativa (HS) is a chronic relapsing disease of follicular occlusion that causes immense clinical and psychosocial morbidity when refractory to treatment. HS is no longer considered a disease of primary infectious etiology, although bacteria play a role. There is increasing evidence that HS is associated with immune dysregulation, based on its clinical association with other immune-mediated disorders, by its response to biologic therapy in the clinical arena, and from molecular research. This article summarizes what is known in relation to the inflammatory pathways in HS.