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Sample records for active chronic sarcoidosis

  1. Chronic cutaneous lesions of sarcoidosis.

    PubMed

    Marchell, Richard M; Judson, Marc A

    2007-01-01

    Sarcoidosis involvement of the skin is common. The skin lesions of sarcoidosis may be nonspecific, showing a nondiagnostic inflammatory reaction pattern on histologic evaluation. Nonspecific skin lesions are often associated with an acute presentation of sarcoidosis and, in general, portend a good prognosis. Specific sarcoidosis skin lesions reveal typical sarcoid granulomas on histologic examination. These lesions tend to be chronic and require therapy for resolution. This article will review the epidemiology, diagnostic evaluation, and description of the various chronic skin lesions of sarcoidosis. Various images of these skin lesions will be demonstrated.

  2. Sarcoidosis

    MedlinePlus

    ... page from the NHLBI on Twitter. What Is Sarcoidosis? Español Sarcoidosis (sar-koy-DO-sis) is a ... Content: NEXT >> Featured Video Living With and Managing Sarcoidosis 05/18/2011 This video—presented by the ...

  3. Sarcoidosis

    MedlinePlus

    Sarcoidosis is a disease that leads to inflammation, usually in your lungs, skin, or lymph nodes. It starts as tiny, grain-like lumps, called granulomas. Sarcoidosis can affect any organ in your body. No ...

  4. Sarcoidosis and chronic beryllium disease: similarities and differences.

    PubMed

    Mayer, Annyce S; Hamzeh, Nabeel; Maier, Lisa A

    2014-06-01

    Chronic beryllium disease (CBD) is a granulomatous lung disease that may be pathologically and clinically indistinguishable from pulmonary sarcoidosis, except through use of immunologic testing, such as the beryllium lymphocyte proliferation test (BeLPT). Similar to sarcoidosis, the pulmonary manifestations of CBD are variable and overlap with other respiratory diseases. Definitive diagnosis of CBD is established by evidence of immune sensitization to beryllium and diagnostic bronchoscopy with bronchoalveolar lavage and transbronchial biopsy. However, the diagnosis of CBD can also be established on a medically probable basis in beryllium-exposed patients with consistent radiographic imaging and clinical course. Beryllium workers exposed too much higher levels of beryllium in the past demonstrated a much more fulminant disease than is usually seen today. Some extrapulmonary manifestations similar to sarcoidosis were noted in these historic cohorts, although with a narrower spectrum. Extrapulmonary manifestations of CBD are rare today. Since lung-predominant sarcoidosis can very closely resemble CBD, CBD is still misdiagnosed as sarcoidosis when current or past exposure to beryllium is not recognized and no BeLPT is obtained. This article describes the similarities and differences between CBD and sarcoidosis, including clinical and diagnostic features that can help physicians consider CBD in patients with apparent lung-predominant sarcoidosis.

  5. Sarcoidosis

    MedlinePlus

    ... the elbow Sarcoidosis on the nose and forehead Respiratory system References Judson MA, Morgenthau AS, Baughman RP. Sarcoidosis. In: Broaddus VC, Mason RJ, Ernst JD, et al, eds. Murray and Nadel's Textbook of Respiratory Medicine . 6th ed. Philadelphia, PA: Elsevier Saunders; 2016: ...

  6. Pulmonary granulomatous reaction: talc pneumoconiosis or chronic sarcoidosis?

    PubMed Central

    Tukiainen, P; Nickels, J; Taskinen, E; Nyberg, M

    1984-01-01

    A chronic pulmonary granulomatous reaction was associated with an almost identical clinical picture in two patients exposed to talc. In both patients lung biopsy showed the deposition of talc particles and a heavy granulomatous reaction. At the time of diagnosis the Kveim test result was negative in both patients, urinary calcium excretion was normal, and there were no extrapulmonary manifestations and no response to steroid treatment. These findings point against sarcoidosis. The serum angiotensin-converting enzyme level, however, was raised in both patients. It was concluded that the patient who was exposed to talc in the rubber industry had a true talc pneumoconiosis. The other patient, who was exposed to cosmetic talcum powder, suffered from chronic sarcoidosis with talc deposition in the lungs, since an enlarged axillar lymph node containing granulomatous inflammation was discovered after two years' follow up. These cases show that it may be extremely difficult to differentiate between chronic sarcoidosis and talc pneumoconiosis even after careful clinical and histological analysis. Images PMID:6691939

  7. Isolated Gastrointestinal Sarcoidosis Involving Multiple Gastrointestinal Sites Presenting as Chronic Diarrhea

    PubMed Central

    Gaye, Bilkisu; Makary, Raafat; Monteiro, Carmela; Eid, Emely

    2016-01-01

    Sarcoidosis is a chronic and systemic disorder characterized by the formation of non-caseating granulomas. Very few cases of isolated gastrointestinal sarcoidosis have been reported, and even fewer, if any, report gastrointestinal sarcoidosis within multiple gastrointestinal sites concomitantly. We present a 42-year-old white man with chronic diarrhea and abdominal pain for more than 3 years. Mucosal biopsies revealed non-caseating microgranulomas in the stomach, throughout the small intestine, colon, and rectum. Prednisone therapy was initiated with a rapid improvement in symptoms and complete resolution of diarrhea within 3 weeks. PMID:28119949

  8. Subcutaneous sarcoidosis.

    PubMed

    Marcoval, Joaquim; Moreno, Abelardo; Mañá, Juan; Peyri, Jordi

    2008-10-01

    Subcutaneous sarcoidosis has been reported to occur in 1.4% to 6% of patients with systemic sarcoidosis. Most reported cases are in women, most often in their fifth and sixth decades, and appear as multiple, asymptomatic, hardly indurated subcutaneous nodules without changes in the overlying epidermis. The lesions are characteristically located in the upper extremities, mainly in the forearms, and usually are bilateral and asymmetric. In most cases the lesions appear at the beginning of systemic sarcoidosis and are not associated with chronic fibrotic disease. Histopathologically, sarcoidosis is characterized by noncaseating naked granulomas involving fat lobules, with minimal to no septal involvement.

  9. [Physiopathology of sarcoidosis].

    PubMed

    Soler, Paul

    2008-05-31

    Sarcoidosis results from an uncontrolled cell-mediated immune reaction involving activated T cells and monocytes-macrophages, characterized by the formation of typical granulomas at the sites of the lesions. The interactions between both cell types induce the release of several mediators that play a central role in the development of granulomas, allowing to design new therapies. The aetiology of sarcoidosis remains unknown, but the disease is currently viewed as the consequence of a chronic immunological response associating a genetic susceptibility and specific environmental factors.

  10. Increased disease activity in a patient with sarcoidosis after high dose interleukin 2 treatment for metastatic renal cancer.

    PubMed

    Logan, T F; Bensadoun, E S

    2005-07-01

    Sarcoidosis is a disease of unknown aetiology in which cytokines such as interleukin 2 (IL-2) are thought to play an important role. We present the case history of a 48 year old man with sarcoidosis who received treatment with high dose IL-2 for metastatic renal cell cancer, following which he developed hypercalcaemia characterised by a raised level of 1,25-dihydroxyvitamin D (1,25-(OH)2-D3), a finding consistent with sarcoidosis associated hypercalcaemia. The increased activity in his sarcoidosis following IL-2 treatment provides direct supportive evidence for the role of IL-2 in the pathogenesis of sarcoidosis.

  11. Search for chronic beryllium disease among sarcoidosis patients in Ontario, Canada.

    PubMed

    Ribeiro, Marcos; Fritscher, Leandro G; Al-Musaed, Ahmed M; Balter, Meyer S; Hoffstein, Victor; Mazer, Bruce D; Maier, Lisa A; Liss, Gary M; Tarlo, Susan M

    2011-06-01

    Chronic beryllium disease (CBD) is clinically similar to other granulomatous diseases such as sarcoidosis. It is often misdiagnosed if a thorough occupational history is not taken. When appropriate, a beryllium lymphocyte proliferation tests (BeLPT) need to be performed. We aimed to search for CBD among currently diagnosed pulmonary sarcoidosis patients and to identify the occupations and exposures in Ontario leading to CBD. Questionnaire items included work history and details of possible exposure to beryllium. Participants who provided a history of previous work with metals underwent BeLPTs and an ELISPOT on the basis of having a higher pretest probability of CBD. Among 121 sarcoid patients enrolled, 87 (72%) reported no known previous metal dust or fume exposure, while 34 (28%) had metal exposure, including 17 (14%) with beryllium exposure at work or home. However, none of these 34 who underwent testing had positive test results. Self-reported exposure to beryllium or metals was relatively common in these patients with clinical sarcoidosis, but CBD was not confirmed using blood assays in this population.

  12. New molecular targets for the treatment of sarcoidosis

    PubMed Central

    Chiarchiaro, Jared; Chen, Bill B.; Gibson, Kevin F.

    2016-01-01

    Purpose of review Sarcoidosis is a chronic granulomatous disease typically affecting the lung, lymph nodes, and other organ systems. Evidence suggests that the morbidity and mortality rates for sarcoidosis in the USA are rising, despite widespread use of anti-inflammatory therapies. In this review, we survey new therapies that target specific inflammatory pathways in other diseases (such as rheumatoid arthritis, Crohn’s disease, and psoriasis) that are similar to pathways relevant to sarcoidosis immunopathogenesis, and therefore, represent potentially new sarcoidosis therapies. Recent findings Immunopathogenesis of sarcoidosis has been well elucidated over the past few years. There is abundant evidence for T-cell activation in sarcoidosis leading to activation of both Th1 and Th17 inflammatory cascades. Therapies targeting T-cell activation, Th1 pathways (such as the interleukin-6 inhibitors), Th17 pathway mediators, and others have been Food and Drug Administration approved or under investigation to treat a variety of autoimmune inflammatory diseases, but have not been studied in sarcoidosis. Targeting the p38 mitogen-activated protein kinases and the ubiquitine proteasome system with new agents may also represent a novel therapeutic option for patients with sarcoidosis. Summary Rising morbidity and mortality rates for patients with sarcoidosis strongly support the need to develop more effective anti-inflammatory therapies to treat chronic disease. PMID:27454074

  13. Pleural sarcoidosis: a rare presentation

    PubMed Central

    Loughney, E.; Higgins, B. G.

    1997-01-01

    Sarcoidosis is a chronic disorder of unknown aetiology which causes tissue injury and granuloma formation in many organs. Although over 80% of cases have intrathoracic disease at presentation, pleural sarcoidosis remains an unusual manifestation. A case of sarcoidosis presenting with a discrete pleural mass is reported. 




 PMID:9059488

  14. Serum ACE Level in Sarcoidosis Patients with Typical and Atypical HRCT Manifestation

    PubMed Central

    Kahkouee, Shahram; Samadi, Katayoon; Alai, Ali; Abedini, Atefeh; Rezaiian, Lida

    2016-01-01

    Summary Background Sarcoidosis is an inflammatory disease that affects multiple organs. Before widespread use of computed tomography (CT), the severity of sarcoidosis was assessed based on chest X-ray abnormalities. HRCT can distinguish between active inflammatory changes and irreversible fibrosis. In this study, we analyzed different ACE levels in 148 patients diagnosed with sarcoidosis. Material/Methods We categorized these patients based on their HRCT results into four groups: 1) patients diagnosed with chronic disease; 2) patients diagnosed with non-chronic disease; 3) patients who exhibited typical HRCT changes; and 4) patients who exhibited atypical HRCT changes. Afterward the mean ACE level of each group was calculated and compared. Result The HRCT scans of chronic sarcoidosis patients tended to show more atypical sarcoidosis patterns. Moreover, there was a reverse correlation between chronicity and ACE level (P-value <0.05). Conclusions HRCT is another modality which would be useful when the diagnosis of sarcoidosis is not definite. PMID:27733890

  15. Sarcoidosis Quiz

    MedlinePlus

    ... Share this page from the NHLBI on Twitter. Sarcoidosis Quiz Sarcoidosis is a disease of unknown cause that leads ... various organs in the body. The outcome of sarcoidosis varies. The disease leads to organ damage in ...

  16. Diagnosis of sarcoidosis

    SciTech Connect

    Sharma, O.P.

    1983-07-01

    During the last decade, many biochemical and immunologic advances have been made in the treatment and understanding of sarcoidosis. These studies have helped us to understand the basic mechanisms involved in granuloma formation, and many clinicians have used the information to diagnose and assess the activity of sarcoidosis. Further studies are needed to clearly establish the role of these advances in the everyday management of patients with sarcoidosis.

  17. Prostate-Specific Membrane Antigen PET/CT: Uptake in Lymph Nodes With Active Sarcoidosis.

    PubMed

    Dias, André Henrique; Holm Vendelbo, Mikkel; Bouchelouche, Kirsten

    2017-03-01

    We describe 2 cases of Ga-PSMA PET/CT in prostate cancer patients. Both cases demonstrated symmetrical bilateral involvement of mediastinal and hilar lymph nodes besides findings in relation with prostatic disease. In both cases, endobronchial ultrasound-guided biopsy showed that the involvement of the thoracic lymph nodes was caused by nonnecrotic granulomas compatible with sarcoidosis. The cases demonstrated that increased Ga-PSMA uptake can be seen in lymph nodes with active sarcoidosis, with images mimicking those well known from FDG PET/CT. Because of these findings, granulomatous disease has to be included in the differential diagnostic evaluation of patients with Ga-PSMA-positive lymph nodes.

  18. Pathogenesis of Sarcoidosis

    PubMed Central

    Gundy, Karl Van; Sharma, Om P.

    1987-01-01

    Sarcoidosis is a multisystem granulomatous disease of unknown etiology. The organs that are involved by sarcoidosis include the lungs in which the granuloma is seen in more than 90% of patients to the pituitary, which is only rarely affected. There are many hypotheses as to the cause of sarcoidosis. Some of them rely on the similarities seen between sarcoidosis and the other granuloma-forming diseases such as tuberculosis, berylliosis, pine pollen inhalation and acute and chronic bacterial and viral infections, while others find similarities between sarcoidosis and immune reactions observed in autoimmune disorders. Still other explanations implicate a genetic predisposition or a still-unknown agent as the underlying cause of the granuloma formation. Images PMID:3310401

  19. Recent advances in sarcoidosis.

    PubMed

    Morgenthau, Adam S; Iannuzzi, Michael C

    2011-01-01

    Sarcoidosis, a systemic granulomatous disease of undetermined etiology, is characterized by a variable clinical presentation and course. During the past decade, advances have been made in the study of sarcoidosis. The multicenter ACCESS (A Case Control Etiologic Study of Sarcoidosis) trial recruited > 700 subjects with newly diagnosed sarcoidosis and matched control subjects. Investigators were unable to identify a single cause of sarcoidosis, but ACCESS paved the way for subsequent etiologic studies. The Mycobacterium tuberculosis catalase-peroxidase protein has been identified as a potential sarcoidosis antigen. Genetic aspects of the disease have been elucidated further. Genome-wide scans have identified candidate genes. Gene expression analyses have defined cytokine dysregulation in sarcoidosis more clearly. Although the criteria for diagnosis have not changed, sarcoidosis remains a diagnosis of exclusion best supported by a tissue biopsy specimen that demonstrates noncaseating granulomas in a patient with compatible clinical and radiologic features of the disease. Endobronchial ultrasound-guided transbronchial needle aspiration of mediastinal lymph nodes has facilitated diagnosis, often eliminating the need for more invasive procedures, such as mediastinoscopy. PET scanning has proven valuable in locating occult sites of active disease. Currently, no reliable prognostic biomarkers have been identified. The tumor necrosis factor inhibitors, a relatively new class of agents, have been used in patients with refractory disease. It is unclear whether phosphodiesterase-5 inhibitors, prostaglandin analogs, or endothelin antagonists should be used for the treatment of sarcoidosis-associated pulmonary hypertension.

  20. Extensive upper respiratory tract sarcoidosis.

    PubMed

    Soares, Mafalda Trindade; Sousa, Carolina; Garanito, Luísa; Freire, Filipe

    2016-04-18

    Sarcoidosis is a chronic granulomatous disease of unknown aetiology. It can affect any part of the organism, although the lung is the most frequently affected organ. Upper airway involvement is rare, particularly if isolated. Sarcoidosis is a diagnosis of exclusion, established by histological evidence of non-caseating granulomas and the absence of other granulomatous diseases. The authors report a case of a man with sarcoidosis manifesting as a chronic inflammatory stenotic condition of the upper respiratory tract and trachea.

  1. Cardiac Sarcoidosis

    MedlinePlus

    ... sarcoidosis. Sarcoidosis is characterized by the presence of granulomas. These are ball-like collections of white blood ... to a foreign substance. The inflammation associated with granulomas can damage every part of the heart, including ...

  2. Musculoskeletal involvement in sarcoidosis*, **

    PubMed Central

    Nessrine, Akasbi; Zahra, Abourazzak Fatima; Taoufik, Harzy

    2014-01-01

    Sarcoidosis is a multisystem inflammatory disorder of unknown cause. It most commonly affects the pulmonary system but can also affect the musculoskeletal system, albeit less frequently. In patients with sarcoidosis, rheumatic involvement is polymorphic. It can be the presenting symptom of the disease or can appear during its progression. Articular involvement is dominated by nonspecific arthralgia, polyarthritis, and Löfgren's syndrome, which is defined as the presence of lung adenopathy, arthralgia (or arthritis), and erythema nodosum. Skeletal manifestations, especially dactylitis, appear mainly as complications of chronic, multiorgan sarcoidosis. Muscle involvement in sarcoidosis is rare and usually asymptomatic. The diagnosis of rheumatic sarcoidosis is based on X-ray findings and magnetic resonance imaging findings, although the definitive diagnosis is made by anatomopathological study of biopsy samples. Musculoskeletal involvement in sarcoidosis is generally relieved with nonsteroidal anti-inflammatory drugs or corticosteroids. In corticosteroid-resistant or -dependent forms of the disease, immunosuppressive therapy, such as treatment with methotrexate or anti-TNF-α, is employed. The aim of this review was to present an overview of the various types of osteoarticular and muscle involvement in sarcoidosis, focusing on their diagnosis and management. PMID:24831403

  3. Corticosteroid Responsive Sarcoidosis with Multisystemic Involvement Years after Initial Diagnosis: A Lymphoma Mimicker on 18-FDG PET/CT

    PubMed Central

    Acar, Turker; Savas, Recep; Kocacelebi, Kenan; Ucan, Eyup Sabri

    2015-01-01

    Sarcoidosis is a chronic multisystemic inflammatory disease characterized by noncaseating epithelioid cell granulomas. 18-Fluorodeoxyglucose positron-emission tomography/computer tomography (FDG-PET/CT) is increasingly used in routine clinical practice to assess active sarcoidosis because it can detect active inflammatory granulomatous disease. However, active sarcoidosis lesions are observed to be hypermetabolic on FDG-PET/CT much like malignancies, which may lead to misinterpretation on imaging. In this case report, we present a rare case of sarcoidosis with multisystem involvement including lung, lymph nodes, bone, pleura, and soft tissue that mimicked lymphoma on FDG-PET/CT and responded to corticosteroid treatment. PMID:26312138

  4. Chronic signaling via the metabolic checkpoint kinase mTORC1 induces macrophage granuloma formation and marks sarcoidosis progression.

    PubMed

    Linke, Monika; Pham, Ha Thi Thanh; Katholnig, Karl; Schnöller, Thomas; Miller, Anne; Demel, Florian; Schütz, Birgit; Rosner, Margit; Kovacic, Boris; Sukhbaatar, Nyamdelger; Niederreiter, Birgit; Blüml, Stephan; Kuess, Peter; Sexl, Veronika; Müller, Mathias; Mikula, Mario; Weckwerth, Wolfram; Haschemi, Arvand; Susani, Martin; Hengstschläger, Markus; Gambello, Michael J; Weichhart, Thomas

    2017-03-01

    The aggregation of hypertrophic macrophages constitutes the basis of all granulomatous diseases, such as tuberculosis or sarcoidosis, and is decisive for disease pathogenesis. However, macrophage-intrinsic pathways driving granuloma initiation and maintenance remain elusive. We found that activation of the metabolic checkpoint kinase mTORC1 in macrophages by deletion of the gene encoding tuberous sclerosis 2 (Tsc2) was sufficient to induce hypertrophy and proliferation, resulting in excessive granuloma formation in vivo. TSC2-deficient macrophages formed mTORC1-dependent granulomatous structures in vitro and showed constitutive proliferation that was mediated by the neo-expression of cyclin-dependent kinase 4 (CDK4). Moreover, mTORC1 promoted metabolic reprogramming via CDK4 toward increased glycolysis while simultaneously inhibiting NF-κB signaling and apoptosis. Inhibition of mTORC1 induced apoptosis and completely resolved granulomas in myeloid TSC2-deficient mice. In human sarcoidosis patients, mTORC1 activation, macrophage proliferation and glycolysis were identified as hallmarks that correlated with clinical disease progression. Collectively, TSC2 maintains macrophage quiescence and prevents mTORC1-dependent granulomatous disease with clinical implications for sarcoidosis.

  5. Cardiac Sarcoidosis.

    PubMed

    Birnie, David; Ha, Andrew C T; Gula, Lorne J; Chakrabarti, Santabhanu; Beanlands, Rob S B; Nery, Pablo

    2015-12-01

    Studies suggest clinically manifest cardiac involvement occurs in 5% of patients with pulmonary/systemic sarcoidosis. The principal manifestations of cardiac sarcoidosis (CS) are conduction abnormalities, ventricular arrhythmias, and heart failure. Data indicate that an 20% to 25% of patients with pulmonary/systemic sarcoidosis have asymptomatic (clinically silent) cardiac involvement. An international guideline for the diagnosis and management of CS recommends that patients be screened for cardiac involvement. Most studies suggest a benign prognosis for patients with clinically silent CS. Immunosuppression therapy is advocated for clinically manifest CS. Device therapy, with implantable cardioverter defibrillators, is recommended for some patients.

  6. Ocular Sarcoidosis

    PubMed Central

    Pasadhika, Sirichai; Rosenbaum, James T

    2015-01-01

    Sarcoidosis is one of the leading causes of inflammatory eye disease. Ocular sarcoidosis can involve any part of the eye and its adnexal tissues, and may cause uveitis, episcleritis/scleritis, eyelid abnormalities, conjunctival granuloma, optic neuropathy, lacrimal gland enlargement and orbital inflammation. Glaucoma and cataract can be complications from inflammation itself or adverse effects from therapy. Ophthalmic manifestations can be isolated, or associated with other organ involvement. Patients with ocular sarcoidosis can present with a wide range of clinical presentations and severity. Multi-disciplinary approaches are required to achieve the best treatment outcomes for both ocular and systemic manifestations. PMID:26593141

  7. Sarcoidosis Overview

    MedlinePlus

    ... system in the body. People with sarcoidosis develop granulomas (small abnormal clumps of tissue) in certain parts ... staff Tags: bilateral hilar lymphadenopathy, granulomatous uveitis, hepatic granulomas, mediastinal adenopathy, multisystem granulomatous disorder, non-caseating epithelioid ...

  8. Gastric sarcoidosis.

    PubMed Central

    Akinyemi, Emmanuel; Rohewal, Upinder; Tangorra, Matthew; Abdullah, Muhammad

    2006-01-01

    A 58-year-old Jamaican male presented with acute-onset, right-sided facial droop and slurred speech. He had an episode of upper gastrointestinal (GI) bleed on the second day of admission and endoscopy with biopsy of antral ulcer revealed gastric sarcoidosis. This case demonstrates the rare entity of gastric sarcoidosis presenting acutely with an upper GI bleed. Images Figure 1 Figure 2 PMID:16775918

  9. 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.

  10. [Sarcoidosis : Renal manifestations].

    PubMed

    Löffler, C; Bergner, R

    2017-04-12

    Renal involvement in sarcoidosis is much more common than generally assumed from old epidemiological studies and is often only detected when actively searched for. Many patients with renal sarcoidosis present with no or only few symptoms. The diagnostic work-up of sarcoidosis should always include a possible renal involvement. In cases of impaired renal function, proteinuria or a pathological urine sediment, a renal biopsy specimen should be obtained to assess the type, severity and prognosis of the kidney disease. Treatment is primarily based on the use of corticosteroids. Steroid-sparing agents, such as disease-modifying antirheumatic drugs and infliximab can be applied; however, the evidence for efficacy of these therapies is mostly based on case series and expert opinions. Discontinuation of immunosuppression therapy bears a high risk of relapse.

  11. Animal models of sarcoidosis.

    PubMed

    Hu, Yijie; Yibrehu, Betel; Zabini, Diana; Kuebler, Wolfgang M

    2017-03-01

    Sarcoidosis is a debilitating, inflammatory, multiorgan, granulomatous disease of unknown cause, commonly affecting the lung. In contrast to other chronic lung diseases such as interstitial pulmonary fibrosis or pulmonary arterial hypertension, there is so far no widely accepted or implemented animal model for this disease. This has hampered our insights into the etiology of sarcoidosis, the mechanisms of its pathogenesis, the identification of new biomarkers and diagnostic tools and, last not least, the development and implementation of novel treatment strategies. Over past years, however, a number of new animal models have been described that may provide useful tools to fill these critical knowledge gaps. In this review, we therefore outline the present status quo for animal models of sarcoidosis, comparing their pros and cons with respect to their ability to mimic the etiological, clinical and histological hallmarks of human disease and discuss their applicability for future research. Overall, the recent surge in animal models has markedly expanded our options for translational research; however, given the relative early stage of most animal models for sarcoidosis, appropriate replication of etiological and histological features of clinical disease, reproducibility and usefulness in terms of identification of new therapeutic targets and biomarkers, and testing of new treatments should be prioritized when considering the refinement of existing or the development of new models.

  12. Appendicular sarcoidosis mimicking acute appendicitis

    PubMed Central

    Hunjan, Tia; Chaudery, Muzzafer; Zaidi, Ahsan; Beggs, Andrew D

    2012-01-01

    Appendicular sarcoidosis is a very rare cause of acute abdominal pain, with only seven cases reported previously in the literature. A 45-year-old woman, known to have sarcoidosis, presented to the emergency department with a 1-week history of epigastric and right iliac fossa abdominal pain. At diagnostic laparoscopy, an acutely inflamed appendix was found and removed as well as an omental mass which was biopsied. Subsequent histopathological examination of the appendix demonstrated appendicular sarcoidosis without acute appendicitis and chronic inflammatory changes in the omental biopsy. The patients’ symptoms completely resolved postoperatively. It is important to undertake urgent operative intervention in patients with sarcoidosis who present with right iliac fossa pain, owing to the high risk of perforation. PMID:23162022

  13. Musculoskeletal and cutaneous sarcoidosis: exuberant case report*

    PubMed Central

    Haddad, Natalie; de Oliveira, Jayme; Nasser, Kassila da Rosa; Corbett, Ana Maria França; Tebet, Ana Carolina Franco; Reis, Mariana Lacerda Junqueira

    2014-01-01

    Sarcoidosis is a multisystem granulomatous disease of unknown cause. The osteoarticular involvement in sarcoidosis is rare and is often associated with cutaneous and long-standing chronic multisystem disease. More common in black women, osseous sarcoidosis is difficult to diagnose, with an incidence of 3 to 13%. The most characteristic radiological clinical picture evidences rounded, well-defined cysts, with no periosteal reaction and without peripheral sclerosis. The small bones of hands and feet are the most frequently involved sites. This report aims to demonstrate a rare case of osteoarticular sarcoidosis with characteristic clinical presentation, and highlight the importance of detecting osteoarticular involvement in this pathology. PMID:25054759

  14. A rare clinical presentation of sarcoidosis; gingivitis.

    PubMed

    Güzel, Aygül; Köksal, Nurhan; Aydın, Davut; Aslan, Kerim; Gören, Fikret; Karagöz, Filiz

    2013-10-01

    Gingivitis due to sarcoidosis is a relatively rare condition. Gingivitis or isolated gingival involvement may be the first sign of systemic sarcoidosis. We report the case of a 37 year-old woman with isolated gingivitis due to sarcoidosis confirmed by biopsy. Following treatment with a systemic corticosteroid (prednisolone 40 mg/day), all clinical and radiologic findings were completely improved. In cases of chronic and intractable gingivitis, systemic sarcoidosis should be suspected. It should be confirmed with a biopsy, and the patient should be referred to a chest disease clinic to exclude other organ involvement.

  15. How Is Sarcoidosis Diagnosed?

    MedlinePlus

    ... page from the NHLBI on Twitter. How Is Sarcoidosis Diagnosed? Your doctor will diagnose sarcoidosis based on ... Content: NEXT >> Featured Video Living With and Managing Sarcoidosis 05/18/2011 This video—presented by the ...

  16. What Causes Sarcoidosis?

    MedlinePlus

    ... page from the NHLBI on Twitter. What Causes Sarcoidosis? The cause of sarcoidosis isn't known. More ... Content: NEXT >> Featured Video Living With and Managing Sarcoidosis 05/18/2011 This video—presented by the ...

  17. How Is Sarcoidosis Treated?

    MedlinePlus

    ... page from the NHLBI on Twitter. How Is Sarcoidosis Treated? Not everyone who has sarcoidosis needs treatment. ... Content: NEXT >> Featured Video Living With and Managing Sarcoidosis 05/18/2011 This video—presented by the ...

  18. Living with Sarcoidosis

    MedlinePlus

    ... page from the NHLBI on Twitter. Living With Sarcoidosis Sarcoidosis has no cure, but you can take ... Content: NEXT >> Featured Video Living With and Managing Sarcoidosis 05/18/2011 This video—presented by the ...

  19. Foundation for Sarcoidosis Research

    MedlinePlus

    ... a Clinical Trial Our mission is to stop sarcoidosis — join us. The sarcoidosis community needs your help ... receive periodic emails from the Foundation. Foundation For Sarcoidosis Research 1820 W. Webster Ave., Ste 304 Chicago, ...

  20. Overexpression of IL-17RC associated with ocular sarcoidosis

    PubMed Central

    2014-01-01

    Background Sarcoidosis is a chronic inflammatory disease with a systemic granulomatous disorder affecting multiple organs including the eye. Both CD4+ T cell and macrophage have been linked to the pathogenesis of the disease. Methods The expression of IL-17RC was measured using FACS,immunohistochemistry and real-time PCR. Serum level of IL-17 was detected using ELISA. Results An elevated expression of IL-17RC on CD8+ T cells in peripheral blood was found in patients with ocular sarcoidosis as compared to healthy controls. Interestingly, we found a significant increase in the serum level of IL-17 in patients with ocular sarcoidosis as compared to healthy controls, which may be responsible for the induction of IL-17RC on CD8+ cells. In addition, IL-17RC appeared only in the retinal tissue of the patient with clinically active sarcoidosis. Conclusions Our results suggested a potential involvement of IL-17RC+CD8+ T cells in pathogenesis of ocular sarcoidosis. PMID:24885153

  1. Specific (granulomatous) oral lesions of sarcoidosis: report of two cases.

    PubMed

    Marcoval, Joaquim; Mañá, Joan

    2010-05-01

    Sarcoidosis is a multisystemic granulomatous disease of unknown aetiology that usually presents with bilateral hiliar adenopathies, pulmonary infiltrations, and ocular and cutaneous lesions. The specific cutaneous lesions, or granulomatous, are produced in from 9% to 37% of patients with systemic sarcoidosis. Nevertheless, few patients have been described having specific lesions from sarcoidosis in the oral mucous membrane. We present 2 patients with systemic sarcoidosis who developed specific sarcoidosis lesions in the oral mucous membrane. The first patient presented a plaque on the tongue of a chronic nature associated with facial lupus pernio. The second patient presented a rapidly growing nodular lesion on the lower lip that was in fact the presentation sign of the disease. Although infrequent, oral lesions may constitute the first sign of systemic sarcoidosis. For this reason the oral mucous membrane needs to be explored when there is suspicion of sarcoidosis, and systemic sarcoidosis must be included in the differential diagnosis of oral granulomatous lesions.

  2. Cutaneous sarcoidosis.

    PubMed

    Marchell, Richard M; Judson, Marc A

    2010-08-01

    Sarcoidosis is a systemic disease with skin manifestations. Skin manifestations are classified as nonspecific if they are not characterized by granulomatous inflammation and specific if the lesions have granulomas histologically. Erythema nodosum is the most common nonspecific skin manifestation, and it portends a good prognosis. Specific skin lesions have a varied clinical appearance, although often they can be distinguished by their yellow translucent character. Despite the potential variable appearance, there are common clinical presentations. Lupus pernio lesions are nodular violaceous specific skin lesions found predominantly on the face associated with scarring and a poor prognosis. Treatment of cutaneous sarcoidosis is primarily done to avoid scarring and cosmetic disfigurement. Local and systemic corticosteroids are the mainstay of treatment for the disease. Corticosteroid-sparing agents used to manage the disease include antimalarials, methotrexate, and tetracycline antibiotics. Tumor necrosis factor-alpha (TNF-alpha) antagonists such as infliximab may have a role in cutaneous sarcoidosis, especially in refractory cases that are resistant to the standard regimens.

  3. Pediatric Gastrointestinal Sarcoidosis: Successful Treatment with Infliximab

    PubMed Central

    Alawdah, Laila; Nahari, Ahmad; Alshahrani, Dayel; Fagih, Musa; Ghazi, Shahid; Al-Hussaini, Abdulrahman

    2016-01-01

    Gastrointestinal sarcoidosis is a rare disease with very limited data in children. Here we report the first pediatric case of successful treatment with infliximab. The first case was an 8-year-old Saudi girl who presented with fever, weight loss, and abdominal pain that was followed in a few months with hematemesis and development of hepatosplenomegaly. The second case was a 9-year-old Sudanese boy who manifested with vomiting, epigastric pain, and weight loss. On upper endoscopy, both cases demonstrated severe erosive nodular gastric mucosa. Gastric and esophageal biopsies had shown noncaseating granulomatous inflammation. The first case had histopathological evidence of granulomatous hepatitis, and both cases demonstrated lung nodularity on computed tomography chest. The boy had elevated angiotensin-converting enzyme level. Given the multisystem involvement with significant chest findings, tissue findings of granulomatous disease, and negative workup for other causes of granulomatous inflammation, both cases were diagnosed with active disseminated sarcoidosis, and treated with corticosteroids. The girl continued to be symptom-free for 4 years after tapering steroid therapy. The boy had relapses off steroids and the disease was brought into remission for 5 years off steroid therapy by infliximab. Pediatric GI sarcoidosis is a rare disease that exhibits heterogeneity in natural course. The chronic relapsing progressive form of the disease might benefit from infliximab therapy. PMID:27748327

  4. Sarcoidosis and the heart: A review of the literature

    PubMed Central

    Ipek, Emrah; Demirelli, Selami; Ermis, Emrah; Inci, Sinan

    2015-01-01

    Summary Sarcoidosis is a chronic multisystem disorder without any defined etiology. Cardiac sarcoidosis (CS) is detected in 2–7% of patients with sarcoidosis and more than 20% of the cases of sarcoidosis are clinically silent. Cardiac involvement in systemic sarcoidosis (SS) and isolated cardiac sarcoidosis (iCS) are associated with arrhythmia and severe heart failure (HF) and have a poor prognosis. Early diagnosis of CS and prompt initiation of corticosteroid therapy with or without other immunosuppressants is crucial. Electrocardiography, Holter monitoring, and Doppler echocardiography with speckle tracking imaging can serve as the initial steps to diagnosis of CS. Cardiac magnetic resonance (CMR) imaging and positron emission tomography (PET) are promising techniques for both diagnosis and follow-up of CS. This review discusses the main aspects of cardiac involvement in sarcoidosis. PMID:26668777

  5. Central skeletal sarcoidosis: a case report with sustained remission only on methotrexate, and a literature review on the imaging approach, treatment, and assessment of disease activity.

    PubMed

    Sakellariou, Grigorios T; Anastasilakis, Athanasios D; Karanikolas, Dimitrios; Vounotrypidis, Periklis; Berberidis, Charalampos

    2013-01-01

    We report a case of multifocal involvement of the central skeleton in a patient with long-term stage I pulmonary sarcoidosis who experienced sustained clinical remission of musculoskeletal symptoms while on methotrexate (MTX) alone. Concomitant normalization of laboratory tests [inflammatory markers and angiotensin-converting enzyme (ACE) levels] was observed, and improvements were seen in follow-up magnetic resonance imaging (MRI) of the lumbar spine and bone scintigraphy. To date, there are no specific tools for the assessment of skeletal disease activity in sarcoidosis. Our case suggests that inflammatory markers and ACE levels, when initially elevated, bone scintigraphy, and-in the case of vertebral involvement-MRI could serve as such tools. A literature review on the imaging approach, treatment, and disease activity monitoring of skeletal sarcoidosis is also provided.

  6. Tenth international conference on sarcoidosis and other granulomatous disorder

    SciTech Connect

    Johns, C.J.

    1986-01-01

    This book contains papers divided among three sections: Basic Mechanisms of Sarcoidosis; Other Granulomatous Disorders; and Clinical Studies of Sarcoidosis. Some of the paper titles are: Radionuclides in Detecting Active Granuloma Formation: Gallium-67 Scintigraphy and Histopathology with Autoradiographic; a European Survey on the Usefulness of /sup 67/Ga Lung Scans in Assessing Sarcoidosis: Experience in 14 Research Centers in Seven Different Countries; and Reassessing the Standard Chest Radiograph for Intraparenchymal Activity.

  7. [Cutaneous manifestations of sarcoidosis].

    PubMed

    Amschler, K; Seitz, C S

    2017-03-17

    Skin manifestations of sarcoidosis occur in up to 30% of cases. This review summarizes and illustrates in detail the differences between specific and unspecific skin manifestations of sarcoidosis. Important differential diagnoses, such as tuberculosis, cutaneous lymphoma and syphilis have to be excluded. The indications for systemic treatment are primarily determined by the extent of organ involvement and also by the cosmetic impairment.

  8. Expression profiling elucidates a molecular gene signature for pulmonary hypertension in sarcoidosis

    PubMed Central

    Singla, Sunit; Zhou, Tong; Javaid, Kamran; Abbasi, Taimur; Casanova, Nancy; Zhang, Wei; Ma, Shwu-Fan; Wade, Michael S.; Noth, Imre; Sweiss, Nadera J.; Garcia, Joe G. N.

    2016-01-01

    Abstract Pulmonary hypertension (PH), when it complicates sarcoidosis, carries a poor prognosis, in part because it is difficult to detect early in patients with worsening respiratory symptoms. Pathogenesis of sarcoidosis occurs via incompletely characterized mechanisms that are distinct from the mechanisms of pulmonary vascular remodeling well known to occur in conjunction with other chronic lung diseases. To address the need for a biomarker to aid in early detection as well as the gap in knowledge regarding the mechanisms of PH in sarcoidosis, we used genome-wide peripheral blood gene expression analysis and identified an 18-gene signature capable of distinguishing sarcoidosis patients with PH (n = 8), sarcoidosis patients without PH (n = 17), and healthy controls (n = 45). The discriminative accuracy of this 18-gene signature was 100% in separating sarcoidosis patients with PH from those without it. If validated in a large replicate cohort, this signature could potentially be used as a diagnostic molecular biomarker for sarcoidosis-associated PH. PMID:28090288

  9. Budd-Chiari Syndrome: An Unusual Presentation of Multisystemic Sarcoidosis

    PubMed Central

    Bacha, Dhouha; Romdhane, Hayfa; Cheikh, Myriam; Nejma, Houda Ben; BelHadj, Najet

    2015-01-01

    Sarcoidosis is a multisystem granulomatous disease of unknown origin. All organs may be affected. Liver involvement is common but it is rarely symptomatic. Only a few cases of Budd-Chiari syndrome (BCS) secondary to a hepatic sarcoidosis have been described so far. We describe a case of multisystemic sarcoidosis presenting with BCS. A 42-year old female was referred to our department for chronic and anicteric cholestasis. Laboratory and imaging investigations disclosed features of chronic BCS associated with multisystemic sarcoidosis. The positive diagnosis was based on microscopic features, which showed hepatic, gastric and cutaneous non-caseating granulomas. Screening for an underlying thrombophilic disorder was negative. The diagnosis of BCS complicating hepatic sarcoidosis was the most likely. She was put on corticosteroids and anticoagulation therapy. To our knowledge, few cases of sarcoidosis-related BCS have been reported in the literature. In addition to being an uncommon presentation of sarcoidosis, this case illustrates the importance of recognizing an unusual cause of BCS and its therapeutic difficulties. PMID:26900444

  10. Sarcoidosis-lymphoma syndrome.

    PubMed

    Brandy-García, Anahy M; Caminal-Montero, Luis; Fernández-García, María Soledad; Saiz Ayala, Angel; Cabezas-Rodríguez, Ivan; Morante-Bolado, Isla

    A 65 year-old female with a history of sarcoidosis with pulmonary and joint involvement, who after 5 years of diagnosis begins with central nervous system involvement manifesting as diplopia. She presents normal analysis results. In imaging results, a mass is identified in the right intraconal space; it depends of right optic nerve, and shows multiple lymph node involvement. Biopsy was performed diagnosed with large B-cell lymphoma, an atypical form of tumor associated with sarcoidosis.

  11. Occupational Causes of Sarcoidosis

    PubMed Central

    Newman, Kira L.; Newman, Lee S.

    2012-01-01

    Purpose of review Sarcoidosis, the multiorgan, granulomatous disease of unknown etiology, remains mysterious. Several important investigations in the past two years add to accumulating evidence for both occupational and environmental causes of granulomatous inflammation. Recent findings This review considers the most recent studies that contribute to the hypothesis that sarcoidosis occurs when individuals are exposed to foreign antigens and to inorganic particulates that promote inflammation. Major recent findings, such as those emerging from the study of World Trade Center responders, the study of nanoparticles, and cases of work-associated sarcoidosis support the probability that occupational, as well as environmental, exposures to inflammatory stimuli trigger sarcoidosis-like illness. Major recent studies of microbially-rich indoor environments, including moldy indoor workplaces and mycobacterially-contaminated settings, contribute to the evidence that a variety of microbial antigens serve as targets for the hypersensitivity immune response in an inflammatory milieu. Summary There is increasing evidence that sarcoidosis can occur in workplace settings in which there is exposure to both foreign antigens and inorganic triggers of inflammation that promote an exuberant granulomatous immune response. It is likely that sarcoidosis has more than one cause. PMID:22314258

  12. Genetic influences on sarcoidosis.

    PubMed

    Ishihara, M; Ohno, S

    1997-01-01

    To investigate the genetic influences underlying the development of sarcoidosis, HLA class II genotyping was performed in Japanese patients with sarcoidosis and healthy controls using the PCR-RFLP method. The frequencies of both DR52 group antigen-associated alleles (HLA-DRB1*11, -DRB1*12 and -DRB1*14) and DRB1*08 alleles were higher in the patient group, suggesting that the common, specific amino acid residue on the DRB1 molecule of these alleles may determine susceptibility to sarcoidosis. Alternatively, it is possible that another susceptibility gene, linked to these DRB1 alleles, exists within the MHC region. We screened the TNFA, TNFB, HSP70-1 and Hum70t genes around the class III region, as well as the HLA-DMA and -DMB genes in the class II region, for genetic polymorphism in sarcoidosis. None of these genes suggested a susceptibility to sarcoidosis. These studies support the thesis that one of the major genetic factors controlling the development of sarcoidosis is located within the DRB1 locus in the HLA class II region.

  13. Orbital sarcoidosis presenting as diffuse swelling of the lower eyelid.

    PubMed

    Lee, Jeong Kyu; Moon, Nam Ju

    2013-02-01

    The author reports a case of orbital Sarcoidosis in a 70-year-old female that initially presented as diffuse swelling of the lower eyelid. The patient complained of painless swelling of the left lower lid without palpable mass, and a computerized tomography (CT) scan of the orbit was unremarkable. A serum angiotensin converting enzyme level was elevated, and hilar lymphadenopathy was noted on the chest CT. The patient underwent surgical debulking for histologic confirmation, which led to a final diagnosis of sarcoidosis involving the orbital fat. Unexplained chronic eyelid swelling without a mass should be considered a possible ophthalmic manifestation of orbital sarcoidosis.

  14. EEG in Sarcoidosis Patients Without Neurological Findings.

    PubMed

    Bilgin Topçuoğlu, Özgür; Kavas, Murat; Öztaş, Selahattin; Arınç, Sibel; Afşar, Gülgün; Saraç, Sema; Midi, İpek

    2017-01-01

    Sarcoidosis is a multisystem granulomatous disease affecting nervous system in 5% to 10% of patients. Magnetic resonance imaging (MRI) is accepted as the most sensitive method for detecting neurosarcoidosis. However, the most common findings in MRI are the nonspecific white matter lesions, which may be unrelated to sarcoidosis and can occur because of hypertension, diabetes mellitus, smoking, and other inflammatory or infectious disorders, as well. Autopsy studies report more frequent neurological involvement than the ante mortem studies. The aim of this study is to assess electroencephalography (EEG) in sarcoidosis patients without neurological findings in order to display asymptomatic neurological dysfunction. We performed EEG on 30 sarcoidosis patients without diagnosis of neurosarcoidosis or prior neurological comorbidities. Fourteen patients (46.7%) showed intermittant focal and/or generalized slowings while awake and not mentally activated. Seven (50%) of these 14 patients with EEG slowings had nonspecific white matter changes while the other half showed EEG slowings in the absence of MRI changes. We conclude that EEG slowings, when normal variants (psychomotor variant, temporal theta of elderly, frontal theta waves) are eliminated, may be an indicator of dysfunction in brain activity even in the absence of MRI findings. Hence, EEG may contribute toward detecting asymptomatic neurological dysfunction or probable future neurological involvement in sarcoidosis patients.

  15. Coexistence of pulmonary tuberculosis and sarcoidosis: a diagnostic dilemma.

    PubMed

    Mandal, Sanjay Kumar; Ghosh, Sudip; Mondal, Soumya Sarathi; Chatterjee, Sumanta

    2014-12-19

    Tuberculosis and sarcoidosis are multisystem diseases having different aetiology and management; however, they have similar clinical and histological characteristics. Very rarely they may coexist. We report a rare case of a 38-year-old woman who presented with chronic cough, low-grade fever and respiratory distress that was initially diagnosed as miliary tuberculosis. Diagnosis was supported by positive mycobacterial culture and initially responded to antitubercular treatment, but later recurrences led to further investigations and the diagnosis of coexisting sarcoidosis.

  16. Nail Sarcoidosis with and without Systemic Involvement: Report of Two Cases.

    PubMed

    Noriega, Leandro; Criado, Paulo; Gabbi, Tatiana; Avancini, João; Di Chiacchio, Nilton

    2015-09-01

    The most commonly seen nail change in sarcoidosis, often associated with chronic systemic disease, is onychodystrophy. Imaging of hands, feet and chest is of paramount importance when nail sarcoidosis is suspected, for evaluation of bone cysts and pulmonary involvement, respectively. We report 2 cases of sarcoidosis that developed nail involvement - one with pulmonary disease, and the other without any evidence of systemic involvement, which is very rare.

  17. Nail Sarcoidosis with and without Systemic Involvement: Report of Two Cases

    PubMed Central

    Noriega, Leandro; Criado, Paulo; Gabbi, Tatiana; Avancini, João; Di Chiacchio, Nilton

    2015-01-01

    The most commonly seen nail change in sarcoidosis, often associated with chronic systemic disease, is onychodystrophy. Imaging of hands, feet and chest is of paramount importance when nail sarcoidosis is suspected, for evaluation of bone cysts and pulmonary involvement, respectively. We report 2 cases of sarcoidosis that developed nail involvement – one with pulmonary disease, and the other without any evidence of systemic involvement, which is very rare. PMID:27170939

  18. Subacute and Chronic Meningitis

    MedlinePlus

    ... not infections can cause chronic meningitis. They include Sarcoidosis Certain disorders that cause inflammation, such as systemic ... For disorders that are not infections, such as sarcoidosis and Behçet syndrome: Corticosteroids or other drugs that ...

  19. Bidirectional ventricular tachycardia in cardiac sarcoidosis.

    PubMed

    Benjamin, Mina M; Hayes, Kevin; Field, Michael E; Scheinman, Melvin M; Hoffmayer, Kurt S

    2017-02-01

    A 73-year-old man with history of pulmonary sarcoidosis was found to have runs of non-sustained bidirectional ventricular tachycardia (BVT) with two different QRS morphologies on a Holter monitor. Cardiac magnetic resonance delayed gadolinium imaging revealed a region of patchy mid-myocardial enhancement within the left ventricular basal inferolateral myocardium. An 18-fluorodeoxyglucose positron emission tomography (FDG-PET) showed increased uptake in the same area, consistent with active sarcoid, with no septal involvement. Follow-up FDG-PET one year later showed disease progression with new septal involvement. Cardiac sarcoidosis, characterized by myocardial inflammation and interstitial fibrosis that can lead to conduction system disturbance and macro re-entrant arrhythmias, should be considered in differential diagnosis of BVT. BVT may indicate septal involvement with sarcoidosis before the lesions are large enough to be detected radiologically.

  20. Management of extrapulmonary sarcoidosis: challenges and solutions

    PubMed Central

    Al-Kofahi, Khalid; Korsten, Peter; Ascoli, Christian; Virupannavar, Shanti; Mirsaeidi, Mehdi; Chang, Ian; Qaqish, Naim; Saketkoo, Lesley A; Baughman, Robert P; Sweiss, Nadera J

    2016-01-01

    Background Sarcoidosis is a chronic multisystem disease of unknown etiology characterized by noncaseating granulomas that most often involves the lungs, but frequently has extrapulmonary manifestations, which might be difficult to treat in individual patients. Objective To review different disease manifestations, focusing on extrapulmonary organ systems, and to provide treatment options for refractory cases. Materials and methods We performed a literature search using Medline and Google Scholar for individual or combined keywords of “sarcoidosis, extrapulmonary, treatment, kidney, neurosarcoidosis, cardiovascular, gastrointestinal, transplantation, musculoskeletal, rheumatology, arthritis, and skin”. Peer-reviewed articles, including review articles, clinical trials, observational trials, and case reports that were published in English were included. References from retrieved articles were also manually searched for relevant articles. Results and conclusion Isolated involvement of a single organ or organ system is rare in sarcoidosis, and thus all patients must be thoroughly evaluated for additional disease manifestations. Cardiac sarcoidosis and neurosarcoidosis may be life-threatening. Clinicians need to assess patients comprehensively using clinical, laboratory, imaging, and histopathological data to recommend competently the best and least toxic treatment option for the individual patient. PMID:27853374

  1. Sarcoidosis: Rheumatology perspective.

    PubMed

    Yee, Arthur M F

    2016-04-01

    Sarcoidosis is a systemic inflammatory granulomatous disease for which rheumatologists are uniquely trained and qualified to treat. Historically, sarcoidosis has been managed within silos of medical subspecialties, but with increased appreciation of the systemic nature of this disorder and the availability of more therapeutic options, it is clear that a multidisciplinary approach, with the rheumatologist as a key component, can offer more optimal care. This manuscript reviews clinically relevant immunology and pathophysiology, diagnostic issues, management decision-making, and therapeutics in the care of patients with sarcoidosis. Issues particularly relevant to rheumatologists are highlighted. These include aiding in establishing diagnosis; recognition of disease manifestations involving bone, joint, and muscle; management of calcium metabolism and metabolic bone disease; and formulation and implementation of anti-inflammatory and immunomodulatory therapies.

  2. Cryptococcal meningitis complicating sarcoidosis

    PubMed Central

    Leonhard, Sonja E.; Fritz, Daan; van de Beek, Diederik; Brouwer, Matthijs C.

    2016-01-01

    Abstract Background: Cryptococcal meningitis is an uncommon but severe complication of sarcoidosis. Methods: We present 2 patients with cryptococcal meningitis complicating sarcoidosis and compared findings with 38 cases reported in the literature. Results: When analyzing our patients and 38 cases reported in the literature, we found that median age of sarcoidosis patients with cryptococcal meningitis was 39 years (range 30–48); 27 of 33 reported cases (82%) had a history of sarcoidosis. Only 16 of 40 patients (40%) received immunomodulating therapy at the time of diagnosis of cryptococcal meningitis. The diagnosis of cryptococcal meningitis was delayed in 17 of 40 patients (43%), mainly because of the initial suspicion of neurosarcoidosis. Cerebrospinal fluid (CSF) examination showed mildly elevated white blood cell count (range 23–129/mm3). Twenty-nine of 32 cases (91%) had a positive CSF culture for Cryptococcus neoformans and 25 of 27 cases (93%) had a positive CSF C neoformans antigen test. CD4 counts were low in all patients in whom counts were performed (84–228/mL). Twelve patients had an unfavorable outcome (32%), of which 7 died (19%) and 24 patients (65%) had a favorable outcome. The rate of unfavorable outcome in patients with a delayed diagnosis was 7 of 17 (41%) compared to 5 of 28 (21%) in patients in whom diagnosis was not delayed. Conclusion: Cryptococcal meningitis is a rare but life-threatening complication of sarcoidosis. Patients were often initially misdiagnosed as neurosarcoidosis, which resulted in considerable treatment delay and worse outcome. CSF cryptococcal antigen tests are advised in patients with sarcoidosis and meningitis. PMID:27583871

  3. Pulmonary Hypertension in Sarcoidosis.

    PubMed

    Baughman, Robert P; Engel, Peter J; Nathan, Steven

    2015-12-01

    Pulmonary hypertension is a complication of sarcoidosis leading to dyspnea and associated with increased morbidity and mortality. Sarcoidosis-associated pulmonary hypertension (SAPH) can be due to several factors, including vascular involvement by the granulomatous inflammation, compression of the pulmonary arteries by adenopathy, fibrotic changes within the lung, and left ventricular diastolic dysfunction. Several case series have suggested that some patients with SAPH benefit from specific therapy for pulmonary hypertension. A randomized, placebo-controlled trial found 16 weeks' bosentan therapy to be associated with significant improvement in pulmonary artery pressure. Future studies may better define who would respond to treatment of pulmonary hypertension.

  4. [Systemic sarcoidosis: a diagnostic challenge in pediatrics. Case report].

    PubMed

    Díaz Angarita, Tomás; Morales Camacho, William; Lozano Neira, Laura; Plata Ortiz, Jessica; Zárate Taborda, Linda

    2016-10-01

    Sarcoidosis is a granulomatous inflammatory disease of unknown etiology, evidenced most often in young adults, which can compromise several organs, mainly lung, lymph nodes, eyes and skin. The presence of the disease in pediatric population is rare. Denomination in pediatrics is made based on age and clinical manifestations of the patient. The aim of this report is to present a case of systemic sarcoidosis in a pediatric patient without lung involvement with severe extrapulmonary manifestations. Fifteen year old patient who debuted with nonspecific symptoms (emesis, weight loss). Radiographic studies without lung involvement but with findings suggestive of Langerhans cell histiocytosis; however, histopathological report (bone and lymph) showed the presence of chronic granulomatous nonnecrotizing disease, sarcoidosis type. Childhood sarcoidosis is a rare and difficult entity to diagnose, mainly by the lack of specific biomarkers for diagnosis.

  5. Sarcoidosis mimicking a venous ulcer: a case report.

    PubMed

    Joshi, Smita S; Romanelli, Paolo; Kirsner, Robert S

    2009-11-01

    Sarcoidosis--a chronic, multisystem disease of unknown etiology characterized by noncaseating granulomas--may cause ulcerative lesions, particularly in African American women. A case of ulcerative sarcoidosis mimicking a venous ulcer is presented. The patient is a 44-year-old African American hypertensive, obese woman with a nonhealing medially based lower leg ulcer of 3 years' duration clinically consistent with a venous ulcer. The ulcer did not heal with compression therapy and pentoxifylline. Subsequent biopsies showed granulomatous inflammation consistent with sarcoidosis. When intralesional triamcinolone was added to compression therapy, the ulcer resolved after 3 months. Given its propensity toward formation on the lower extremities and ulcerative and atrophic appearance, ulcerative sarcoidosis should be considered in the differential diagnosis of a venous ulcer refractory to standard therapy, especially in African American women.

  6. Who Is at Risk for Sarcoidosis?

    MedlinePlus

    ... NHLBI on Twitter. Who Is at Risk for Sarcoidosis? Sarcoidosis affects people of all ages and races. ... Content: NEXT >> Featured Video Living With and Managing Sarcoidosis 05/18/2011 This video—presented by the ...

  7. Sarcoidosis: Immunopathogenesis and Immunological Markers

    PubMed Central

    Loke, Wei Sheng Joshua; Herbert, Cristan; Thomas, Paul S.

    2013-01-01

    Sarcoidosis is a multisystem granulomatous disorder invariably affecting the lungs. It is a disease with noteworthy variations in clinical manifestation and disease outcome and has been described as an “immune paradox” with peripheral anergy despite exaggerated inflammation at disease sites. Despite extensive research, sarcoidosis remains a disease with undetermined aetiology. Current evidence supports the notion that the immune response in sarcoidosis is driven by a putative antigen in a genetically susceptible individual. Unfortunately, there currently exists no reliable biomarker to delineate the disease severity and prognosis. As such, the diagnosis of sarcoidosis remains a vexing clinical challenge. In this review, we outline the immunological features of sarcoidosis, discuss the evidence for and against various candidate etiological agents (infective and noninfective), describe the exhaled breath condensate, a novel method of identifying immunological biomarkers, and suggest other possible immunological biomarkers to better characterise the immunopathogenesis of sarcoidosis. PMID:26464848

  8. Sarcoidosis, cancer and molecular mimicry.

    PubMed

    Tchernev, G; Wollina, U

    2013-01-01

    Molecular mimicry seems to be the most important factor for the heterogeneous clinical presentation and the immunopathogenesis of sarcoidosis. Molecular mimicry may occur as a result of altered activity of oncogenes. This can lead to crossed-type mediated body reactions targeting structurally similar sections or regions from the tissue homeostasis. Available data suggest that structural analogy between tissue and foreign or de novo-appearing peptides is not always reliable. Nevertheless, lack of amino acid identity between the tissue and the de novo-generated tumour antigens does not exclude the phenomenon of molecular mimicry as the major generator of sarcoidosis. There is growing evidence of the mimicry phenomena, caused not only by the similarity between the amino acids but also between the elements which connect segments in the immunological cascade and which may also be affected by external factors. Molecular mimicry may occur between two identified peptides having similar antigenic surfaces (transitory or not), in the absence of a primary homology in amino acid sequence. As far as tumour antigens are concerned, a structural analogy to the de novo-appearing tumour antigens is more likely than transitory imitation resulting from the additional interference of other physical forces. Further research should be performed to confirm, or reject, the transitory imitation thesis or hypothesis.

  9. Cough in Sarcoidosis.

    PubMed

    Tully, Timothy; Birring, Surinder S

    2016-02-01

    Sarcoidosis is a granulomatous disorder that frequently affects the lungs. Cough is commonly reported by patients and can significantly reduce health-related quality of life. The mechanism of cough is unknown but airway inflammation, mechanical distortion from pulmonary fibrosis and disruption of the vagus nerve are possible. Recent evidence suggests cough reflex hypersensitivity may also be an important mechanism and predictor of the frequency of cough. The investigation of cough should evaluate common causes such as asthma, gastro-oesophageal reflux and rhinitis. In patients with suspected cough due to sarcoidosis, a trial of corticosteroids should be considered. The severity of cough should be evaluated with validated outcome measures such as visual analogue scales, cough severity diary, health-related quality of life questionnaires such as the Leicester Cough Questionnaire and objective cough monitors. Future studies are needed to identify targets for therapeutic development.

  10. [Ocular Manifestations in Sarcoidosis].

    PubMed

    Walscheid, K; Tappeiner, C; Heiligenhaus, A

    2016-05-01

    Sarcoidosis is an inflammatory multi-organ disease of unknown pathogenesis, characterised by non-necrotising granulomata. Sarcoidosis predominantly manifests in the lung, but any other organ may be affected. Ocular involvement is present in about 25 to 50 % of patients. The most common ocular manifestation is uveitis, especially of the anterior eye segment. If ocular sarcoidosis is suspected, interdisciplinary assessment of the patient is mandatory, including laboratory tests, chest X-ray, assessment by a specialist in internal medicine and, ideally, histological evidence of granuloma formation in a tissue specimen. Other (infectious) causes of granulomatous inflammation need to be excluded, especially tuberculosis or syphilis. For the ophthalmological assessment, detection of granulomatous lesions is of particular importance, especially by visualising chorioretinal granuloma by fluorescein and indocyanin green angiography. Cystoid macular oedema and glaucoma are the most frequent complications limiting visual acuity. Corticosteroids, which can be administered either locally or systemically, are the mainstay of therapy. Depending on the clinical course and the development of ocular complications, systemic steroid-sparing immunosuppressive medication may be indicated.

  11. The epidemiology of sarcoidosis

    PubMed Central

    Hall, G.; Sharma, O. P.; Naish, P.; Doe, W.; James, D. Geraint

    1969-01-01

    The nationality, social factors, exposures, morbidity, mortality, and hospital discharge notes have been analysed in a series of patients with histologically proven sarcoidosis, and correlated with clinical and radiological features. Compared with the expected prevalence according to the Central London population obtained from the 1961 Census, Irish and West Indians attended the Sarcoidosis Clinic twice as frequently as British, whereas African Negroes are under-represented. Sarcoidosis is slightly commoner in women, particularly those in the childbearing years of life. Mass miniature radiography rates per 100,000 population reveal prevalence rates of twenty overall, forty-three in those aged 25-34 years, and ten in those aged over 45 years. Erythema nodosum, other skin lesions, and ocular involvement occurred twice as often in women. The death-rate of about 1·7/106 population is slightly higher in women and in those living in rural districts. Hospital discharge rates are about three per 100,000 people at risk each year. PMID:5821184

  12. Beryllium-induced lung disease exhibits expression profiles similar to sarcoidosis

    PubMed Central

    Li, Li; Silveira, Lori J.; Hamzeh, Nabeel; Gillespie, May; Mroz, Peggy M.; Mayer, Annyce S.; Fingerlin, Tasha E.; Maier, Lisa A.

    2016-01-01

    A subset of beryllium-exposed workers develop beryllium sensitisation (BeS) which precedes chronic beryllium disease (CBD). We conducted an in-depth analysis of differentially expressed candidate genes in CBD. We performed Affymetrix GeneChip 1.0 ST array analysis on peripheral blood mononuclear cells (PBMCs) from 10 CBD, 10 BeS and 10 beryllium-exposed, nondiseased controls stimulated with BeSO4 or medium. The differentially expressed genes were validated by high-throughput real-time PCR in this group and in an additional group of cases and nonexposed controls. The functional roles of the top candidate genes in CBD were assessed using a pharmacological inhibitor. CBD gene expression data were compared with whole blood and lung tissue in sarcoidosis from the Gene Expression Omnibus. We confirmed almost 450 genes that were significantly differentially expressed between CBD and controls. The top enrichment of genes was for JAK (Janus kinase)–STAT (signal transducer and activator of transcription) signalling. A JAK2 inhibitor significantly decreased tumour necrosis factor-α and interferon-γ production. Furthermore, we found 287 differentially expressed genes overlapped in CBD/sarcoidosis. The top shared pathways included cytokine–cytokine receptor interactions, and Toll-like receptor, chemokine and JAK–STAT signalling pathways. We show that PBMCs demonstrate differentially expressed gene profiles relevant to the immunnopathogenesis of CBD. CBD and sarcoidosis share similar differential expression of pathogenic genes and pathways. PMID:27103383

  13. Digestive-tract sarcoidosis

    PubMed Central

    Ghrenassia, Etienne; Mekinian, Arsene; Chapelon-Albric, Catherine; Levy, Pierre; Cosnes, Jacques; Sève, Pascal; Lefèvre, Guillaume; Dhôte, Robin; Launay, David; Prendki, Virginie; Morell-Dubois, Sandrine; Sadoun, Danielle; Mehdaoui, Anas; Soussan, Michael; Bourrier, Anne; Ricard, Laure; Benamouzig, Robert; Valeyre, Dominique; Fain, Olivier

    2016-01-01

    Abstract Digestive tract sarcoidosis (DTS) is rare and case-series are lacking. In this retrospective case–control study, we aimed to compare the characteristics, outcome, and treatment of patients with DTS, nondigestive tract sarcoidosis (NDTS), and Crohn disease. We included cases of confirmed sarcoidosis, symptomatic digestive tract involvement, and noncaseating granuloma in any digestive tract. Each case was compared with 2 controls with sarcoidoisis without digestive tract involvement and 4 with Crohn disease. We compared 25 cases of DTS to 50 controls with NDTS and 100 controls with Crohn disease. The major digestive clinical features were abdominal pain (56%), weight loss (52%), nausea/vomiting (48%), diarrhea (32%), and digestive bleeding (28%). On endoscopy of DTS, macroscopic lesions were observed in the esophagus (9%), stomach (78%), duodenum (9%), colon, (25%) and rectum (19%). As compared with NDTS, DTS was associated with weight loss (odds ratio [OR] 5.8; 95% confidence interval [CI] 1.44–23.3) and the absence of thoracic adenopathy (OR 5.0; 95% CI 1.03–25). As compared with Crohn disease, DTS was associated with Afro-Caribbean origin (OR 27; 95% CI 3.6–204) and the absence of ileum or colon macroscopic lesions (OR 62.5; 95% CI 10.3–500). On the last follow-up, patients with DTS showed no need for surgery (versus 31% for patients with Crohn disease; P = 0.0013), and clinical digestive remission was frequent (76% vs. 35% for patients with Crohn disease; P = 0.0002). The differential diagnosis with Crohn disease could be an issue with DTS. Nevertheless, the 2 diseases often have different clinical presentation and outcome. PMID:27442665

  14. Childhood sarcoidosis: Louisiana experience.

    PubMed

    Gedalia, Abraham; Khan, Tahir A; Shetty, Avinash K; Dimitriades, Victoria R; Espinoza, Luis R

    2016-07-01

    A retrospective chart review was conducted to detect patients with sarcoidosis seen by pediatric rheumatology service from the period of 1992 to 2013 at Children's hospital of New Orleans. Twenty-seven patients were identified. The average duration of symptoms before diagnosis was 5 (range 1-120) months. Five patients had onset before the age of 5 years and were diagnosed with early-onset sarcoidosis. The most common manifestations at presentation were constitutional symptoms (62 %) followed by ocular (38 %). During the course of illness, 19/27 (70 %) had multiorgan involvement. Common manifestations included uveitis/iritis (77 %), fever (50 %), hilar adenopathy (42 %), arthritis (31 %), peripheral lympadenopathy (31 %), hepatosplenomegaly (31 %), parenchymal lung disease (27 %), and skin rash (19 %). Unusual manifestations included granulomatous bone marrow disease (3 cases), hypertension (2), abdominal aortic aneurysm (large vessel vasculitis; 1), granulomatous hepatitis (1), nephrocalcinosis (1), membranous nephropathy (1), refractory granulomatous interstitial nephritis with recurrence in transplanted kidney (1), CNS involvement (2), parotid gland enlargement (1), and sensorineural hearing loss (1). Biopsy specimen was obtained in 21/27 (77 %) patients, and demonstration of noncaseating granuloma associated with negative stains for mycobacteria and fungi was seen in 18 patients. Elevated angiotensin-converting enzyme level was seen in 74 % of patients. Treatment with oral prednisone was initiated in symptomatic patients with significant clinical improvement. Low-dose methotrexate (MTX) 10-15 mg/m(2)/week orally, as steroid-sparing agent, was administered in 14 patients. Other immunomodulators included cyclophosphamide (2 patients), etanercept (2), infliximab (2), mycophenolate mofetil (1), and tacrolimus (1). Childhood sarcoidosis is prevalent in Louisiana. Most of the affected children present with a multisystem disease associated with

  15. Serum angiotensin converting enzyme activity in chronic beryllium disease.

    PubMed

    Newman, L S; Orton, R; Kreiss, K

    1992-07-01

    Serum angiotensin converting enzyme (SACE) activity is used as a marker of sarcoidosis activity and severity, but in chronic beryllium disease (CBD) the studies of SACE give conflicting results. We examined SACE activity in 23 CBD patients, five patients with beryllium sensitization, and 25 beryllium-exposed control subjects. CBD patients underwent complete clinical evaluation, including physical examination, pulmonary function testing, exercise physiology testing, chest radiography, and bronchoscopy with bronchoalveolar lavage and biopsy. CBD SACE activity was systematically compared with these clinical markers of disease severity. Of CBD patients, 22% had elevated SACE activity. The test did not discriminate CBD patients from those in the beryllium-sensitized or beryllium-exposed groups. However, SACE activity in CBD correlated with the extent of pulmonary granulomatous inflammation as reflected by the symptom of breathlessness, the number of white cells in bronchoalveolar lavage (r = 0.44), the number of lavage lymphocytes (r = 0.58), the lavage lymphocyte percentage (r = 0.55), and the profusion of small opacities on chest radiograph (r = 0.41). The test-retest reliability of the assay was high (r = 0.84), as was the agreement between fresh and -70 degrees C frozen sera (r = 0.93). We conclude that SACE activity levels may reflect the extent of pulmonary granulomatous inflammation in CBD but that the test does not help discriminate disease from nondisease.

  16. Lichenoid sarcoidosis: a case with clinical and histopathological lichenoid features.

    PubMed

    Garrido-Ruiz, Maria C; Enguita-Valls, Ana B; de Arriba, Marta González; Vanaclocha, Francisco; Peralto, Jose Luis Rodriguez

    2008-06-01

    Sarcoidosis is a chronic multisystemic granulomatous disease of unknown etiology, characterized by the formation of noncaseating granulomas in the involved organs. Cutaneous involvement is about 25% with different clinical expressions, the lichenoid pattern being one of the rarest types of cutaneous sarcoidosis. Lichenoid sarcoidosis clinically manifests with multiple scale papules involving extensive skin areas, especially the trunk, limbs, and face mimicking a lichen planus. Although diverse histologic patterns have been previously related, a lichenoid granulomatous infiltrate involving the dermo-epidermal junction has never been reported in lichenoid sarcoidosis. We report a case of a 43-year-old woman presenting with skin-colored pruritic papules, slightly scaling in trunk, extremities, and ears. These symptoms condition continued to expand and worsen for several years. The patient was otherwise in good health with no lymphadenopathies. Histopathologic examination of a skin biopsy showed an upper dermal granulomatous infiltrate of epithelioid cells, without necrosis, distributed in a lichenoid pattern with many cytoid bodies. We consider this may be the first case presenting a characteristic microscopic granulomatous lichen-like pattern in the setting of a clinically lichenoid type of sarcoidosis.

  17. Detection of HTLV-I proviral DNA in sarcoidosis.

    PubMed

    Yajima, A; Kawada, A; Aragane, Y; Tezuka, T

    2001-01-01

    'Sarcoidosis-lymphoma syndrome' is known as an association of sarcoidosis with malignant lymphoma. We report a 56-year-old woman with systemic sarcoidosis who was seropositive for antibody against human T cell lymphoma/leukemia virus type I (HTLV-I). This patient showed integration of HTLV-I proviral DNA within cutaneous sarcoid nodules, but not in peripheral blood mononuclear cells. Neither atypical lymphocytes nor a T cell receptor beta1 gene rearrangement were observed in peripheral blood mononuclear cells or in cutaneous nodules, indicating that the patient did not have a smouldering type of adult T cell lymphoma/leukemia. Detection of integration of HTLV-I proviral DNA in cutaneous sarcoid nodules could suggest that the sarcoid nodules might have been generated as a protective response to chronic stimuli of HTLV-I.

  18. Upper Airway Obstruction Requiring Emergent Tracheostomy Secondary to Laryngeal Sarcoidosis: A Case Report

    PubMed Central

    Ryu, Changwan; Herzog, Erica L.; Pan, Hongyi; Homer, Robert; Gulati, Mridu

    2017-01-01

    Patient: Female, 35 Final Diagnosis: Laryngeal sarcoidosis Symptoms: Hoarseness • stridor Medication: — Clinical Procedure: Tracheostomy Specialty: Otolaryngology Objective: Rare disease Background: Laryngeal sarcoidosis is a rare extrapulmonary manifestation of sarcoidosis, accounting for 0.33–2.1% of cases. A life-threatening complication of laryngeal sarcoidosis is upper airway obstruction. In this report we describe our experience in the acute and chronic care of a patient who required an emergent tracheostomy, with the aim to provide further insight into this difficult to manage disease. Case Report: A 37-year-old African American female with a 10-year history of stage 1 sarcoidosis presented with severe dyspnea. Laryngeal sarcoidosis was diagnosed three years previously, and she remained stable on low-dose prednisone until six months prior to admission, at which time she self-discontinued her prednisone for the homeopathic treatment Nopalea cactus juice. Her physical examination was concerning for impending respiratory failure as she presented with inspiratory stridor and hoarseness. Laryngoscopy showed a retroflexed epiglottis obstructing the glottis with edematous arytenoids and aryepiglottic folds. Otolaryngology performed an emergent tracheostomy to secure her airway and obtained epiglottic biopsies, which were consistent with sarcoidosis. She was eventually discharged home on prednisone 60 mg daily. Following months of corticosteroids, a laryngoscopy showed the epiglottis continuing to obstruct the glottis. The addition of methotrexate to a tapered dosage of prednisone 10 mg daily was unsuccessful, and she remains on prednisone 20 mg daily for disease control. Conclusions: Laryngeal sarcoidosis, a rare extrapulmonary manifestation of sarcoidosis, uncommonly presents as the life-threatening complication of complete upper airway obstruction. As such, laryngeal sarcoidosis is associated with significant morbidity and mortality, requiring a high index

  19. Talc granulomatosis mimicking sarcoidosis.

    PubMed

    Iqbal, A; Aggarwal, B; Menon, B; Kulshreshtha, R

    2008-07-01

    Pulmonary disease due to talc, a group of hydrous magnesium silicates, is almost exclusively encountered secondary to occupational exposure or intravenous drug abuse. Talcosis or talc pneumoconiosis is one of the rarer forms of silicate-induced lung disease. It is seen in workers exposed during its production, and occasionally, in users of cosmetic talc and in intravenous drug addicts. Very often, the history of exposure is not recognised by the patient, and it is only the finding of granulomatous cellular interstitial lesions containing birefringent crystals which indicates considerable talc exposure. We report a 38-year-old woman who was initially diagnosed with sarcoidosis, until a bronchoscopic biopsy revealed the presence of numerous foreign body giant cells and birefringent particles forming non-caseating granulomas. There was no history of occupational exposure to talc or intravenous drug abuse. The patient responded to oral corticosteroid treatment. Talcosis is generally considered to be relatively benign.

  20. Sarcoidosis in celiac disease: A page written by genetic variants in IL-18 miRNAs target site?

    PubMed

    Mormile, Raffaella

    2016-05-01

    Sarcoidosis is a chronic idiopathic granulomatous disease. Interleukin-18 (IL-18) has been strongly implicated in the pathogenesis of sarcoidosis. Sarcoidosis shows characteristic microRNAs (miRNAs) profiles. MiRNAs have recently emerged as a new class of modulators of gene expression. MiRNAs are involved in susceptibility to a number of autoimmune diseases promoting and inhibiting the gene expression of different Th1 pro-inflammatory cytokines including IL18. Sarcoidosis has been connected with a variety of autoimmune disorders including celiac disease (CD). CD is a chronic, immune-mediated condition of the small intestine caused by permanent intolerance to dietary gluten. IL-18 has been reported to play an important role in inducing and maintaining inflammation after gluten exposure. MiRNAs expression is significantly altered in CD patients. We hypothesize that sarcoidosis and CD may be the result of common genetic variants in IL-18 miRNA target site.

  1. Sarcoidosis presenting with multiple tattoo granulomata

    PubMed Central

    Iveson, J. M. I.; Cotterill, J. A.; Wright, V.

    1975-01-01

    A patient with sarcoidosis, multiple tattoo granulomata and arthritis is described. A combination of tattoo granulomata unrelated to any one colour in the tattoo and granulomatous inflammation elsewhere is indicative of sarcoidosis. ImagesFig. 1Fig. 2 PMID:1197172

  2. An atypical sarcoidosis involvement in FDG PET/CT

    PubMed Central

    Robin, Philippe; Benigni, Paolo; Feger, Benoit; Salaun, Pierre-Yves; Abgral, Ronan

    2016-01-01

    Abstract Rationale: Sarcoidosis is an idiopathic systemic inflammatory granulomatous disorder comprised of epithelioid and multinucleated giant cells with little necrosis which involve various organs. Laryngeal involvement is extremely rare, with a prevalence of about 0.5 to 1%. Diagnoses: Here we present a case of laryngeal involvement of sarcoidosis demonstrated on 18F-Fluorodesoxyglucose Positron-Emission Tomography/Computed Tomography (FDG PET/CT). Patient concerns: A 63 year-old man suffering from dysphonia was referred to our department for characterization of laryngeal lesion suspicious for cancer with non-informative biopsy, the sample was not sufficient for diagnosis. Interventions: FDG PET/CT showed a pathological uptake on the right vocal cord, but also highlighted a bilateral uptake in intrathoracic hilar lymphadenopathy areas, typically found in several inflammatory diseases. Outcomes: New laryngeal targeted biopsies revealed non-caseating epithelioid granulomas suggesting sarcoidosis involvement. After 6 months of systemic steroid treatment, FDG PET/CT showed a significant decrease of the laryngeal uptake. Lessons: This case shows the usefulness of FDG PET/CT to accurately assess inflammatory activity in rare extra-pulmonary sarcoidosis involvement. Moreover, this case emphasizes that FDG PET/CT is an interesting tool for assessing therapeutic efficacy of inflammatory diseases such as sarcoidosis. PMID:28033265

  3. Ultrasound findings in cutaneous sarcoidosis

    PubMed Central

    Dybiec, Ewa; Pietrzak, Aldona; Kieszko, Robert; Kanitakis, Jean

    2015-01-01

    The diagnosis of cutaneous sarcoidosis relies mainly on the patient's history, presence of characteristic skin lesions and histological examination that shows a granulomatous, non-necrotizing dermal infiltration. The aim of the study was to assess the ultrasonographic features of cutaneous lesions of sarcoidosis before and after treatment. A 38-year-old woman with systemic sarcoidosis and specific cutaneous lesions was treated with systemic steroids followed by hydroxychloroquine. Ultrasonographic examination of the cutaneous sarcoidosis lesions was performed with a Philips iU 22 and Siemens Acuson S 2000 device, with the use of linear 15 MHz and 17 MHz transducers. Histological examination of skin lesions showed characteristic, naked, non-necrotizing granulomas in the upper dermis. Ultrasound examination revealed well-demarcated, hypoechogenic changes. Power-Doppler scan revealed increased vascularity within the lesions and the surrounding tissue. Clinical improvement of the skin lesions was confirmed by ultrasound examination, which showed a decrease in their size and normalization of dermal echogenicity and vascularity. Ultrasound examination can show cutaneous sarcoidosis lesions and their regression after appropriate treatment. PMID:25821428

  4. Upper Airway Obstruction Requiring Emergent Tracheostomy Secondary to Laryngeal Sarcoidosis: A Case Report.

    PubMed

    Ryu, Changwan; Herzog, Erica L; Pan, Hongyi; Homer, Robert; Gulati, Mridu

    2017-02-13

    BACKGROUND Laryngeal sarcoidosis is a rare extrapulmonary manifestation of sarcoidosis, accounting for 0.33-2.1% of cases. A life-threatening complication of laryngeal sarcoidosis is upper airway obstruction. In this report we describe our experience in the acute and chronic care of a patient who required an emergent tracheostomy, with the aim to provide further insight into this difficult to manage disease. CASE REPORT A 37-year-old African American female with a 10-year history of stage 1 sarcoidosis presented with severe dyspnea. Laryngeal sarcoidosis was diagnosed three years previously, and she remained stable on low-dose prednisone until six months prior to admission, at which time she self-discontinued her prednisone for the homeopathic treatment Nopalea cactus juice. Her physical examination was concerning for impending respiratory failure as she presented with inspiratory stridor and hoarseness. Laryngoscopy showed a retroflexed epiglottis obstructing the glottis with edematous arytenoids and aryepiglottic folds. Otolaryngology performed an emergent tracheostomy to secure her airway and obtained epiglottic biopsies, which were consistent with sarcoidosis. She was eventually discharged home on prednisone 60 mg daily. Following months of corticosteroids, a laryngoscopy showed the epiglottis continuing to obstruct the glottis. The addition of methotrexate to a tapered dosage of prednisone 10 mg daily was unsuccessful, and she remains on prednisone 20 mg daily for disease control. CONCLUSIONS Laryngeal sarcoidosis, a rare extrapulmonary manifestation of sarcoidosis, uncommonly presents as the life-threatening complication of complete upper airway obstruction. As such, laryngeal sarcoidosis is associated with significant morbidity and mortality, requiring a high index of suspicion for timely diagnosis and treatment.

  5. Hepatic sarcoidosis: a case series

    PubMed Central

    Ennaifer, Rym; Ayadi, Shema; Romdhane, Hayfa; Cheikh, Myriam; Nejma, Houda Ben; Bougassas, Wassila; Hadj, Najet Bel

    2016-01-01

    Sarcoidosis is a systemic non caseous granulomas disease. Liver is a common location but usually asymptomatic. Evidence based guidelines for this location treatment is lacking and the effect of corticosteroids may be inadequate. The aim of our study was to describe the clinical, biochemical, radiological and therapeutic features of seven patients with systemic sarcoidosis and liver involvement. A retrospective and descriptive monocentric study, over 3 years, including seven patients with systemic sarcoidosis and liver involvement. We included 5 women and 2 men with an average age of 43 years. Hepatic localization revealed sarcoidosis in 5 cases. Hepatomegaly was observed in all patients as well as abnormal serum liver function test reflected by anicteric cholestasis. Liver biopsy, showed in all granulomatous lesions consistent with sarcoidosis and severe fibrosis in 2 cases. Extra-hepatic manifestations were present in all patients represented mainly by pulmonary location. All patients were treated, five by corticosteroid and two with ursodeoxycholic acid (UDCA). Complete response was observed in one case, partial response in another case and corticosteroid refractoriness in one case. In two cases, corticosteroid therapy was introduced for less than 1 month, not allowing assessment of response. Antimalarials in combination with UDCA were used successfully in a patient with steroid-resistant liver disease. Liver involvement can reveal systemic sarcoidois. Given the risk of progression to severe liver disease, it must be screened in all patients with systemic sarcoidosis. Treatment is not systematic, and still based on corticosteroid therapy. In the absence of prospective randomized controlled trials, the efficacy of UDCA need to be proven. PMID:27795804

  6. Sarcoidosis associated with neuromyelitis optica.

    PubMed

    Sawaya, Raja; Radwan, Wael

    2013-08-01

    Neuromyelitis optica (NMO) is an autoimmune disorder diagnosed by an elongated spinal cord lesion associated with unilateral or bilateral optic neuritis and anti-aquaporin 4 (AQP4) antibodies in the serum. It is triggered by or associated with several autoimmune diseases, but not with sarcoidosis. It responds to immunomodulators better than to steroid treatment. Sarcoidosis is an autoimmune disorder which manifests as non-caseating granulomas, usually in the lung parenchyma, but also in other tissues, including the brain. The involvement of the central nervous system in neurosarcoidosis differs considerably from that in neuromyelitis optica and the association of these two diseases concurrently in the same patient is unusual.

  7. Muscular Sarcoidosis Detected by F-18 FDG PET/CT in a Hypercalcemic Patient

    PubMed Central

    Han, Eun Ji; Jang, Yi Sun; Lee, In Suk; Lee, Jong Min; Kang, Siwon

    2013-01-01

    Sarcoidosis is a systemic granulomatous disease of unknown etiology that involves many organs, occasionally mimicking malignancy. We herein report a 50-yr-old woman of muscular sarcoidosis of chronic myopathic type, manifested by hypercalcemia and muscle wasting. Besides insignificant hilar lymphadenopathy, her sarcoidosis was confined to generalized atrophic muscles and therefore, F-18 FDG PET/CT alone among conventional imaging studies provided diagnostic clues for the non-parathyroid-related hypercalcemia. On follow-up PET/CT during low-dose steroid treatment, FDG uptake in the muscles disappeared whereas that in the hilar lymph nodes remained. PET/CT may be useful in the evaluation of unexpected disease extent and monitoring treatment response in suspected or known sarcoidosis patients. PMID:24015050

  8. Sarcoidosis in patients with mixed connective tissue disease: clinical, genetic, serological and histological observations.

    PubMed

    Szodoray, Peter; Szollosi, Zoltan; Gyimesi, Edit; Takacs, Istvan; Mekkel, Gabriella; Vegh, Judit; Szilagyi, Anna; Zeher, Margit; Szegedi, Gyula; Bodolay, Edit

    2008-06-01

    The objective of this study was to investigate how the development of sarcoidosis influences the disease course of mixed connective tissue disease (MCTD). The cellular composition of MCTD-associated sarcoidosis granulomas was evaluated and also the disease-accompanying T-cell activation and alterations of the serum cytokine levels were measured before and after the therapy. The HLA-DR specific alleles were also assessed. We present two cases with MCTD coexisting sarcoidosis. Serum concentrations of Th1 and Th2 cytokines were assessed by ELISA. Peripheral blood CD3+ total T-cell numbers, CD4+ and CD8+ T-cell subset were determined by flow cytometry. Furthermore, hematoxylin-eosin staining and immunhistochemistry were performed for histological assessment. HLA-DR specific alleles were determined by using PCR-SSP. Elevated number of activated T-cells and high Th1 cytokine levels were detected, mainly IFN-gamma and TNF-alpha. Histologically, CD4+ and CD8+ T-cells were present in the sarcoidosis infiltrations. The haplotypes were to some extent dissimilar from the HLA-DR genotype from patients with MCTD, or sarcoidosis alone. Sarcoidosis enhances the activation of MCTD, based on the laboratory and clinical findings. Our results show that the inflammation is mainly in the effector phase, while granuloma formation is characteristic of the resolution phase of the disease. The assessment of the cytokine network in sarcoidosis-associated MCTD enables us to select the most effective, individualized therapy protocol for these patients.

  9. Gallium scan in intracerebral sarcoidosis

    SciTech Connect

    Makhija, M.C.; Anayiotos, C.P.

    1981-07-01

    Sarcoidosis involving the nervous system probably occurs in about 4% of patients. The usefulness of brain scintigraphy in these cases has been suggested. In this case of cerebral sarcoid granuloma, gallium imaging demonstrated the lesion before treatment and showed disappearance of the lesion after corticosteroid treatment, which correlated with the patient's clinical improvement.

  10. Cardiac sarcoidosis: diagnosis and management.

    PubMed

    Dubrey, S W; Sharma, R; Underwood, R; Mittal, T

    2015-07-01

    Cardiac sarcoidosis is one of the most serious and unpredictable aspects of this disease state. Heart involvement frequently presents with arrhythmias or conduction disease, although myocardial infiltration resulting in congestive heart failure may also occur. The prognosis in cardiac sarcoidosis is highly variable, which relates to the heterogeneous nature of heart involvement and marked differences between racial groups. Electrocardiography and echocardiography often provide the first clue to the diagnosis, but advanced imaging studies using positron emission tomography and MRI, in combination with nuclear isotope perfusion scanning are now essential to the diagnosis and management of this condition. The identification of clinically occult cardiac sarcoidosis and the management of isolated and/or asymptomatic heart involvement remain both challenging and contentious. Corticosteroids remain the first treatment choice with the later substitution of immunosuppressive and steroid-sparing therapies. Heart transplantation is an unusual outcome, but when performed, the results are comparable or better than heart transplantation for other disease states. We review the epidemiology, developments in diagnostic techniques and the management of cardiac sarcoidosis.

  11. What Are the Signs and Symptoms of Sarcoidosis?

    MedlinePlus

    ... Twitter. What Are the Signs and Symptoms of Sarcoidosis? Many people who have sarcoidosis have no signs ... symptom is more common in women than men. Sarcoidosis Signs and Symptoms The illustration shows the major ...

  12. Gene expression profiles in granuloma tissue reveal novel diagnostic markers in sarcoidosis.

    PubMed

    Christophi, George P; Caza, Tiffany; Curtiss, Christopher; Gumber, Divya; Massa, Paul T; Landas, Steve K

    2014-06-01

    Sarcoidosis is an immune-mediated multisystem disease characterized by the formation of non-caseating granulomas. The pathogenesis of sarcoidosis is unclear, with proposed infectious or environmental antigens triggering an aberrant immune response in susceptible hosts. Multiple pro-inflammatory signaling pathways have been implicated in mediating macrophage activation and granuloma formation in sarcoidosis, including IFN-γ/STAT-1, IL-6/STAT-3, and NF-κB. It is difficult to distinguish sarcoidosis from other granulomatous diseases or assess disease severity and treatment response with histopathology alone. Therefore, development of improved diagnostic tools is imperative. Herein, we describe an efficient and reliable technique to classify granulomatous disease through selected gene expression and identify novel genes and cytokine pathways contributing to the pathogenesis of sarcoidosis. We quantified the expression of twenty selected mRNAs extracted from formalin-fixed paraffin embedded (FFPE) tissue (n = 38) of normal lung, suture granulomas, sarcoid granulomas, and fungal granulomas. Utilizing quantitative real-time RT-PCR we analyzed the expression of several genes, including IL-6, COX-2, MCP-1, IFN-γ, T-bet, IRF-1, Nox2, IL-33, and eotaxin-1 and revealed differential regulation between suture, sarcoidosis, and fungal granulomas. This is the first study demonstrating that quantification of target gene expression in FFPE tissue biopsies is a potentially effective diagnostic and research tool in sarcoidosis.

  13. Sarcoidosis of the upper and lower airways.

    PubMed

    Morgenthau, Adam S; Teirstein, Alvin S

    2011-12-01

    Sarcoidosis is a systemic granulomatous disease of undetermined etiology characterized by a variable clinical presentation and disease course. Although clinical granulomatous inflammation may occur within any organ system, more than 90% of sarcoidosis patients have lung disease. Sarcoidosis is considered an interstitial lung disease that is frequently characterized by restrictive physiologic dysfunction on pulmonary function tests. However, sarcoidosis also involves the airways (large and small), causing obstructive airways disease. It is one of a few interstitial lung diseases that affects the entire length of the respiratory tract - from the nose to the terminal bronchioles - and causes a broad spectrum of airways dysfunction. This article examines airway dysfunction in sarcoidosis. The anatomical structure of the airways is the organizational framework for our discussion. We discuss sarcoidosis involving the nose, sinuses, nasal passages, larynx, trachea, bronchi and small airways. Common complications of airways disease, such as, atelectasis, fibrosis, bullous leions, bronchiectasis, cavitary lesions and mycetomas, are also reviewed.

  14. HLA-DRB1*1101: A Significant Risk Factor for Sarcoidosis in Blacks and Whites

    PubMed Central

    Rossman, Milton D.; Thompson, Bruce; Frederick, Margaret; Maliarik, Mary; Iannuzzi, Michael C.; Rybicki, Benjamin A.; Pandey, Janardan P.; Newman, Lee S.; Magira, Eleni; Beznik-Cizman, Bojana; Monos, Dimitri

    2003-01-01

    Sarcoidosis is a granulomatous disorder of unknown etiology, associated with an accumulation of CD4+ T cells and a TH1 immune response. Since previous studies of HLA associations with sarcoidosis were limited by serologic or low-resolution molecular identification, we performed high-resolution typing for the HLA-DPB1, HLA-DQB1, HLA-DRB1, and HLA-DRB3 loci and the presence of the DRB4 or DRB5 locus, to define HLA class II associations with sarcoidosis. A Case Control Etiologic Study of Sarcoidosis (ACCESS) enrolled biopsy-confirmed cases (736 total) from 10 centers in the United States. Seven hundred six (706) controls were case matched for age, race, sex, and geographic area. We studied the first 474 ACCESS patients and case-matched controls. The HLA-DRB1 alleles were differentially distributed between cases and controls (P<.0001). The HLA-DRB1*1101 allele was associated (P<.01) with sarcoidosis in blacks and whites and had a population attributable risk of 16% in blacks and 9% in whites. HLA-DRB1-F47 was the amino acid residue most associated with sarcoidosis and independently associated with sarcoidosis in whites. The HLA-DPB1 locus also contributed to susceptibility for sarcoidosis and, in contrast to chronic beryllium disease, a non–E69-containing allele, HLA-DPB1*0101, conveyed most of the risk. Although significant differences were observed in the distribution of HLA class II alleles between blacks and whites, only HLA-DRB1*1501 was differentially associated with sarcoidosis (P<.003). In addition to being susceptibility markers, HLA class II alleles may be markers for different phenotypes of sarcoidosis (DRB1*0401 for eye in blacks and whites, DRB3 for bone marrow in blacks, and DPB1*0101 for hypercalcemia in whites). These studies confirm a genetic predisposition for sarcoidosis and present evidence for the allelic variation at the HLA-DRB1 locus as a major contributor. PMID:14508706

  15. HLA-DRB1*1101: a significant risk factor for sarcoidosis in blacks and whites.

    PubMed

    Rossman, Milton D; Thompson, Bruce; Frederick, Margaret; Maliarik, Mary; Iannuzzi, Michael C; Rybicki, Benjamin A; Pandey, Janardan P; Newman, Lee S; Magira, Eleni; Beznik-Cizman, Bojana; Monos, Dimitri

    2003-10-01

    Sarcoidosis is a granulomatous disorder of unknown etiology, associated with an accumulation of CD4+ T cells and a TH1 immune response. Since previous studies of HLA associations with sarcoidosis were limited by serologic or low-resolution molecular identification, we performed high-resolution typing for the HLA-DPB1, HLA-DQB1, HLA-DRB1, and HLA-DRB3 loci and the presence of the DRB4 or DRB5 locus, to define HLA class II associations with sarcoidosis. A Case Control Etiologic Study of Sarcoidosis (ACCESS) enrolled biopsy-confirmed cases (736 total) from 10 centers in the United States. Seven hundred six (706) controls were case matched for age, race, sex, and geographic area. We studied the first 474 ACCESS patients and case-matched controls. The HLA-DRB1 alleles were differentially distributed between cases and controls (P<.0001). The HLA-DRB1*1101 allele was associated (P<.01) with sarcoidosis in blacks and whites and had a population attributable risk of 16% in blacks and 9% in whites. HLA-DRB1-F(47) was the amino acid residue most associated with sarcoidosis and independently associated with sarcoidosis in whites. The HLA-DPB1 locus also contributed to susceptibility for sarcoidosis and, in contrast to chronic beryllium disease, a non-E(69)-containing allele, HLA-DPB1*0101, conveyed most of the risk. Although significant differences were observed in the distribution of HLA class II alleles between blacks and whites, only HLA-DRB1*1501 was differentially associated with sarcoidosis (P<.003). In addition to being susceptibility markers, HLA class II alleles may be markers for different phenotypes of sarcoidosis (DRB1*0401 for eye in blacks and whites, DRB3 for bone marrow in blacks, and DPB1*0101 for hypercalcemia in whites). These studies confirm a genetic predisposition for sarcoidosis and present evidence for the allelic variation at the HLA-DRB1 locus as a major contributor.

  16. An oral lesion as the primary clinical manifestation of sarcoidosis.

    PubMed

    Gill, I; Siddiqi, J

    2017-03-16

    An oral lesion as the first clinical presentation of sarcoidosis is extremely rare. We present the case of a 39-year-old woman who was referred to the oral and maxillofacial surgery department with a persistent asymptomatic nodular lesion in the hard palate. This was located adjacent to a grossly carious upper first molar and a provisional diagnosis of chronic periapical granuloma was made. An incisional biopsy of the lesion was carried out, which unexpectedly revealed the presence of a non-caseating granulomatous inflammatory reaction. A referral was sent to the respiratory medicine team and a diagnosis was later confirmed of stage II sarcoidosis. This case report highlights the need for clinicians to be aware of all possible causes of oral lesions, including rare manifestations of underlying systemic disease.

  17. Sarcoidosis of the peripheral nervous system.

    PubMed

    Said, Gérard

    2013-01-01

    Neurological manifestations of sarcoidosis are relatively rare but constitute a treatable cause of central and peripheral neurological manifestations. Regarding the peripheral nervous system, cranial nerves are predominantly affected, and peripheral facial nerve palsy, often bilateral, is the most common neurological manifestation of sarcoidosis. Multifocal peripheral neuropathy is a rare event in sarcoidosis. In some cases, however, peripheral neuropathy is the presenting manifestation and seemingly the only organ affected. Definite diagnosis of sarcoidosis rests ideally on histological demonstration of sarcoid granulomas in tissue biopsy specimens.

  18. Transcriptional Blood Signatures Distinguish Pulmonary Tuberculosis, Pulmonary Sarcoidosis, Pneumonias and Lung Cancers

    PubMed Central

    Bloom, Chloe I.; Graham, Christine M.; Berry, Matthew P. R.; Rozakeas, Fotini; Redford, Paul S.; Wang, Yuanyuan; Xu, Zhaohui; Wilkinson, Katalin A.; Wilkinson, Robert J.; Kendrick, Yvonne; Devouassoux, Gilles; Ferry, Tristan; Miyara, Makoto; Bouvry, Diane; Dominique, Valeyre; Gorochov, Guy; Blankenship, Derek; Saadatian, Mitra; Vanhems, Phillip; Beynon, Huw; Vancheeswaran, Rama; Wickremasinghe, Melissa; Chaussabel, Damien; Banchereau, Jacques; Pascual, Virginia; Ho, Ling-pei; Lipman, Marc; O’Garra, Anne

    2013-01-01

    Rationale New approaches to define factors underlying the immunopathogenesis of pulmonary diseases including sarcoidosis and tuberculosis are needed to develop new treatments and biomarkers. Comparing the blood transcriptional response of tuberculosis to other similar pulmonary diseases will advance knowledge of disease pathways and help distinguish diseases with similar clinical presentations. Objectives To determine the factors underlying the immunopathogenesis of the granulomatous diseases, sarcoidosis and tuberculosis, by comparing the blood transcriptional responses in these and other pulmonary diseases. Methods We compared whole blood genome-wide transcriptional profiles in pulmonary sarcoidosis, pulmonary tuberculosis, to community acquired pneumonia and primary lung cancer and healthy controls, before and after treatment, and in purified leucocyte populations. Measurements and Main Results An Interferon-inducible neutrophil-driven blood transcriptional signature was present in both sarcoidosis and tuberculosis, with a higher abundance and expression in tuberculosis. Heterogeneity of the sarcoidosis signature correlated significantly with disease activity. Transcriptional profiles in pneumonia and lung cancer revealed an over-abundance of inflammatory transcripts. After successful treatment the transcriptional activity in tuberculosis and pneumonia patients was significantly reduced. However the glucocorticoid-responsive sarcoidosis patients showed a significant increase in transcriptional activity. 144-blood transcripts were able to distinguish tuberculosis from other lung diseases and controls. Conclusions Tuberculosis and sarcoidosis revealed similar blood transcriptional profiles, dominated by interferon-inducible transcripts, while pneumonia and lung cancer showed distinct signatures, dominated by inflammatory genes. There were also significant differences between tuberculosis and sarcoidosis in the degree of their transcriptional activity, the

  19. PSMA Uptake in Mediastinal Sarcoidosis.

    PubMed

    Ardies, Philip Junior; Gykiere, Pieterjan; Goethals, Lode; De Mey, Johan; De Geeter, Frank; Everaert, Hendrik

    2017-04-01

    Prostate-specific membrane antigen (PSMA) is a cell surface glycoprotein which is frequently overexpressed on prostate cancer cells. Ga-PSMA PET/CT plays an increasing role in prostate cancer management. However, growing evidence suggests increased PSMA uptake in a variety of other malignant tumor entities and in some benign lesions. This report describes PSMA uptake in numerous thoracic lymph nodes in a patient with known mediastinal sarcoidosis. Knowledge and recognition of these possibilities are important to avoid scan misinterpretation.

  20. Ninth International Conference on Sarcoidosis.

    DTIC Science & Technology

    1981-10-15

    some neoplasms, extrinsic allergic alveolitis (e.g., farmer’s lung, bird fancier’s lung, bagassosis) and miscellaneous disorders such as sebaceous...SUPPLEMENTARY NOTES 19. KEY WORDS (Continue on reverse side if necesery mnd identify by block nuatbor) ACE lymphocytes alveolitis sarcoidosis...emphasis on immunologic aspects. Confining discussion to the lung, he pointed out that the granuloma there is preceded by alveolitis , an inflammatory

  1. Multimodality Imaging in Cardiac Sarcoidosis: Is There a Winner?

    PubMed Central

    Perez, Irving E.; Garcia, Mario J.; Taub, Cynthia C.

    2016-01-01

    Sarcoidosis is a multisystem granulomatous disease of unknown cause that can affect the heart. Cardiac sarcoidosis may be present in as many as 25% of patients with systemic sarcoidosis, and it is frequently underdiagnosed. The early and accurate diagnosis of myocardial involvement is challenging. Advanced imaging techniques play important roles in the diagnosis and management of patients with cardiac sarcoidosis. PMID:25784137

  2. Reduced expression of monocyte CD200R is associated with enhanced proinflammatory cytokine production in sarcoidosis

    PubMed Central

    Fraser, Simon D.; Sadofsky, Laura R.; Kaye, Paul M.; Hart, Simon P.

    2016-01-01

    In sarcoidosis, the proinflammatory cytokines interferon gamma, tumour necrosis factor and interleukin-6 are released by monocyte-derived macrophages and lymphocytes in the lungs and other affected tissues. Regulatory receptors expressed on monocytes and macrophages act to suppress cytokine production, and reduced expression of regulatory receptors may thus promote tissue inflammation. The aim of this study was to characterise the role of regulatory receptors on blood monocytes in patients with sarcoidosis. Cytokine release in response to stimulation of whole blood was measured in healthy controls and Caucasian non-smoking patients with sarcoidosis who were not taking disease modifying therapy. Expression of the regulatory molecules IL-10R, SIRP-α/β, CD47, CD200R, and CD200L was measured by flow cytometry, and functional activity was assessed using blocking antibodies. Stimulated whole blood and monocytes from patients with sarcoidosis produced more TNF and IL-6 compared with healthy controls. 52.9% of sarcoidosis patients had monocytes characterised by low expression of CD200R, compared with 11.7% of controls (p < 0.0001). Patients with low monocyte CD200R expression produced higher levels of proinflammatory cytokines. In functional studies, blocking the CD200 axis increased production of TNF and IL-6. Reduced expression of CD200R on monocytes may be a mechanism contributing to monocyte and macrophage hyper-activation in sarcoidosis. PMID:27929051

  3. Biopsy proven pituitary sarcoidosis presenting as a possible adenoma.

    PubMed

    Prayson, Richard A

    2016-12-01

    Sarcoidosis is a well-recognized systemic granulomatous process which involves the central nervous system in 5-15% of patients. One of the more frequent sites of central nervous system involvement is the pituitary and hypothalamic region. Involvement of the sellar region by sarcoidosis is overall an infrequent occurrence, comprising less than 1% of all intrasellar lesions. Patients typically present with an infiltrative lesion on imaging studies and clinically with symptoms related to diabetes insipidus or hyperprolactinemia. This report describes a 38-year-old woman who initially presented with a variety of symptoms including headaches, light sensitivity, nausea and vomiting, acute visual changes, cold intolerance, amenorrhea, decreased libido, fatigue and galactorrhea. She had an elevated serum prolactin level and evidence of oligoclonal bands in the cerebrospinal fluid. Imaging studies discovered a 1.8cm mass involving the pituitary gland and compressing the optic chiasm. The lesion was excised and microscopically was marked by a chronic inflammatory cell infiltrate and scattered nonnecrotizing granulomas. Stains and microbiologic cultures failed to demonstrate microorganisms. There was no evidence of other organ involvement on postoperative imaging. She was treated with prednisone with improvement of symptoms and subsequently required methotrexate to treat left eye pain and blurred vision, 29months after her surgery. Achieving treatment control in patients with pituitary and hypothalamic improvement in sarcoidosis still remains a challenge.

  4. Insertion/Deletion Polymorphisms and Serum Angiotensin-converting Enzyme Levels in Iranian Patients with Sarcoidosis

    PubMed Central

    JAVADI, Alireza; SHAMAEI, Masoud; ZAREI, Masoud; REZAEIAN, Lida; KIANI, Arda; ABEDINI, Atefeh

    2016-01-01

    Background: Sarcoidosis is a multisystem inflammatory disease of unknown origin with characterization of small granulomas. Angiotensin-converting enzyme (ACE) is a pathophysiologic marker of sarcoidosis. We present the ACE insertion/deletion (I/D) polymorphism in correlation with serum ACE level in Iranian patients with sarcoidosis. Methods: From Jan 2014 to Jan 2015, 102 Iranian patients who histopathologically diagnosed for sarcoidosis and 192 healthy age and sex-matched controls were recruited. PCR was used for detection of I/D polymorphism in ACE gene. Results: Frequency of II/ID/DD genotype in sarcoidosis disease was 17%, 35.5%, and 47.1%, respectively. The frequency of D allele was 0.65. A significant association between I/D genotypes and mean of sACE level was seen (DD=85.2±22.9, P<0.001). More frequent genotype in sarcoidosis patients was DD (47%), ID genotype (45.9%) was found more in controls. Logistic regression analysis adjusting age and sex showed that ID to II (OR=0.35, 95%CI=0.17–0.73, P=0.005) and DD to II (OR=2.11, 95%CI=0.98–4.54, P=0.05) could be considered as a predictor factor for the disease activity. No significant model for men in sarcoidosis group was seen, while women with II/ID were associated with a reduced risk for the disease. Conclusion: Although more regional studies with appropriate statistical scale must be done to provide a better diagnosis and prognostic tool for this disease, this study demonstrates that ID and DD genotype could be predictive factors for sarcoidosis. PMID:28032065

  5. Identification of HLA-DR–bound peptides presented by human bronchoalveolar lavage cells in sarcoidosis

    PubMed Central

    Wahlström, Jan; Dengjel, Jörn; Persson, Bengt; Duyar, Hüseyin; Rammensee, Hans-Georg; Stevanoviδc, Stefan; Eklund, Anders; Weissert, Robert; Grunewald, Johan

    2007-01-01

    Sarcoidosis is an inflammatory disease of unknown etiology, most commonly affecting the lungs. Activated CD4+ T cells accumulate in the lungs of individuals with sarcoidosis and are considered to be of central importance for inflammation. We have previously shown that Scandinavian sarcoidosis patients expressing the HLA-DR allele DRB1*0301 are characterized by large accumulations in the lungs of CD4+ T cells expressing the TCR AV2S3 gene segment. This association afforded us a unique opportunity to identify a sarcoidosis-specific antigen recognized by AV2S3+ T cells. To identify candidates for the postulated sarcoidosis-specific antigen, lung cells from 16 HLA-DRB1*0301pos patients were obtained by bronchoalveolar lavage. HLA-DR molecules were affinity purified and bound peptides acid eluted. Subsequently, peptides were separated by reversed-phase HPLC and analyzed by liquid chromatography–mass spectrometry. We identified 78 amino acid sequences from self proteins presented in the lungs of sarcoidosis patients, some of which were well-known autoantigens such as vimentin and ATP synthase. For the first time, to our knowledge, we have identified HLA-bound peptides presented in vivo during an inflammatory condition. This approach can be extended to characterize HLA-bound peptides in various autoimmune settings. PMID:17975675

  6. Sarcoidosis Extent Relates to Molecular Variability.

    PubMed

    Monast, Calixte S; Li, Katherine; Judson, Marc A; Baughman, Robert P; Wadman, Eric; Watt, Rosemary; Silkoff, Philip E; Barnathan, Elliot S; Brodmerkel, Carrie

    2017-02-16

    The molecular basis of sarcoidosis phenotype heterogeneity and its relationship to effective treatment of sarcoidosis have not been elucidated. Peripheral samples from sarcoidosis subjects who participated in a phase 2 study of golimumab (anti-TNFα) and ustekinumab (anti-IL12p40) were used to measure the whole blood transcriptome and levels of serum proteins. Differential gene and protein expression analyses were used to explore the molecular differences between sarcoidosis phenotypes as defined by extent of organ involvement. The same data were also used in conjunction with an enrichment algorithm to identify gene expression changes associated with treatment with study drugs compared to placebo. Our analyses revealed marked heterogeneity among the three sarcoidosis phenotypes included in the study cohort, including striking differences in enrichment of the Interferon Pathway. Conversely, enrichments of multiple pathways, including T Cell Receptor Signaling, were similar among phenotypes. We also identify differences between treatment with golimumab and ustekinumab that may explain the differences in trends for clinical efficacy observed in the trial. We find that molecular heterogeneity is associated with sarcoidosis in a manner that may be related to the extent of organ involvement. These findings may help explain the difficulty in identifying clinically efficacious sarcoidosis treatments and suggest hypotheses for improved therapeutic strategies. This article is protected by copyright. All rights reserved.

  7. Abdominal sarcoidosis: cross-sectional imaging findings

    PubMed Central

    Gezer, Naciye Sinem; Başara, Işıl; Altay, Canan; Harman, Mustafa; Rocher, Laurence; Karabulut, Nevzat; Seçil, Mustafa

    2015-01-01

    Sarcoidosis is a multisystem inflammatory disease of unknown etiology. The lungs and the lymphoid system are the most commonly involved organs. Extrapulmonary involvement is reported in 30% of patients, and the abdomen is the most common extrapulmonary site with a frequency of 50%–70%. Although intra-abdominal sarcoidosis is usually asymptomatic, its presence may affect the prognosis and treatment options. The lesions are less characteristic and may mimick neoplastic or infectious diseases such as lymphoma, diffuse metastasis, and granulomatous inflammation. The liver and spleen are the most common abdominal sites of involvement. Sarcoidosis of the gastrointestinal system, pancreas, and kidneys are extremely rare. Adenopathy which is most commonly found in the porta hepatis, exudative ascites, and multiple granulomatous nodules studding the peritoneum are the reported manifestations of abdominal sarcoidosis. Since abdominal sarcoidosis is less common and long-standing, unrecognized disease can result in significant morbidity and mortality. Imaging contributes to diagnosis and management of intra-abdominal sarcoidosis. In this report we reviewed the cross-sectional imaging findings of hepatobiliary, gastrointestinal, and genitourinary sarcoidosis. PMID:25512071

  8. [Optic disc granuloma secondary to sarcoidosis].

    PubMed

    Qu-Knafo, L; Auregan-Giocanti, A

    2017-02-01

    We report a case of optic disc granuloma due to sarcoidosis. A 64-year-old, caucasian female with a history of pulmonary sarcoidosis presented with a vision loss on her left eye. The ophthalmologic examination revealed a discrete optic disc infiltrate compatible with the diagnosis of optic disc granuloma. Fluorescein angiography showed diffusion and impregnation of the granuloma without vascularitis. The optical coherence tomography demonstrated a homogenous and isoreflective lesion at the optic disc. The patient recovered her visual acuity after systemic corticosteroid treatment. Isolated optic disc granuloma is a rare condition of ocular sarcoidosis.

  9. Sarcoidosis of the cardio-pulmonary systems.

    PubMed

    Dubrey, Simon; Sharma, Rakesh; Underwood, Richard; Mittal, Tarun; Wells, Athol

    2016-02-01

    Sarcoidosis is a multi-system disease with a wide range of phenotypes. Pulmonary involvement is the most frequently identified target for sarcoidosis and is responsible for the majority of deaths. Cardiac sarcoid is less commonly identified, may be occult, is significantly influenced by race, and can portend an unpredictable and sometimes fatal outcome. Sarcoidosis remains an enigmatic disease spectrum of unknown aetiology, frequently difficult to diagnose and with a variable disease course. This article summarises current views on the diagnosis and management of cardiopulmonary involvement.

  10. Expression Profile of Six RNA-Binding Proteins in Pulmonary Sarcoidosis

    PubMed Central

    Novosadova, Eva; Hagemann-Jensen, Michael; Kullberg, Susanna; Kolek, Vitezslav; Grunewald, Johan; Petrek, Martin

    2016-01-01

    Background Sarcoidosis is characterised by up-regulation of cytokines and chemokine ligands/receptors and proteolytic enzymes. This pro-inflammatory profile is regulated post-transcriptionally by RNA-binding proteins (RBPs). We investigated in vivo expression of six RBPs (AUF1, HuR, NCL, TIA, TIAR, PCBP2) and two inhibitors of proteolytic enzymes (RECK, PTEN) in pulmonary sarcoidosis and compared it to the expression in four control groups of healthy individuals and patients with other respiratory diseases: chronic obstructive pulmonary disease (COPD), asthma and idiopathic interstitial pneumonias (IIPs). Methods RT-PCR was used to quantify the mRNAs in bronchoalveolar (BA) cells obtained from 50 sarcoidosis patients, 23 healthy controls, 30 COPD, 19 asthmatic and 19 IIPs patients. Flow cytometry was used to assess intracellular protein expression of AUF1 and HuR in peripheral blood T lymphocytes (PBTLs) obtained from 9 sarcoidosis patients and 6 healthy controls. Results Taking the stringent conditions for multiple comparisons into consideration, we consistently observed in the primary analysis including all patients regardless of smoking status as well as in the subsequent sub-analysis limited for never smokers that the BA mRNA expression of AUF1 (p<0.001), TIA (p<0.001), NCL (p<0.01) and RECK (p<0.05) was decreased in sarcoidosis compared to healthy controls. TIA mRNA was also decreased in sarcoidosis compared to both obstructive pulmonary diseases (COPD and asthma; p<0.001) but not compared to IIPs. There were several positive correlations between RECK mRNA and RBP mRNAs in BA cells. Also sarcoidosis CD3+, CD4+ and CD8+ PBTLs displayed lower mean fluorescence intensity of AUF1 (p≤0.02) and HuR (p≤0.03) proteins than control healthy PBTLs. Conclusion mRNA expressions of three RBPs (AUF1, TIA and NCL) and their potential target mRNA encoding RECK in BA cells and additionally protein expression of AUF1 and HuR in PBTLs were down-regulated in our sarcoidosis

  11. Subcutaneous sarcoidosis in a rhinoplasty scar

    PubMed Central

    Dulguerov, Nicolas; Vankatova, Lenka; Landis, Basile Nicolas

    2015-01-01

    The presence of a subcutaneous hard bony-like lump at the lateral nasal wall after a septorhinoplasty procedure is an unfavourable result. The reported patient developed this complication 2 years after a revision surgery, in which percutaneous osteotomies were performed. An excision biopsy of the lump took place and the histopathological analysis revealed a granulomatous gigantocellular inflammation with absence of birefringent particles on polarised lamp and negative mycobacteria culture. After additional investigations, the final diagnosis was consistent with grade 2 pulmonary sarcoidosis associated with subcutaneous sarcoidosis. No treatment was initiated. The facial symptoms resolved without any additional treatment and the pulmonary function tests have not deteriorated after 1 year of follow-up. The polymorphism of cutaneous lesions in sarcoidosis, the absence of systemic symptoms and the unrecognised entity of subcutaneous sarcoidosis in a scar illustrate the diagnostic challenge with this patient. PMID:25819832

  12. [Sarcoidosis - diagnosis and therapy today].

    PubMed

    Christ, R

    1980-12-15

    The etiology of sarcoidosis is still unclear. It belongs to the most frequent lung diseases; but also nearly all other tissues and organs may be established. One third of the diseases runs under the picture of the acute form of the course (Loefgren's syndrome). A histologic ascertainment is to be striven for. The tendency to spontaneous remission is great. This is still additionally supported by the application of cortison derivatives. In the individual case the indication to medicamentous therapy results from the tendency of the course of the disease, from the degree of the affection of organs and the clinico-functional disturbance. In 80 patients with Loefgren's syndrome the author adopts a definite attitude to diagnostics and therapy.

  13. Monitoring the Therapy of Extensive Osseous Sarcoidosis With FDG PET/CT.

    PubMed

    Yang, Hua; Numani, Shah; Liu, Shuang

    2017-02-24

    FDG PET/CT was performed in a 47-year-old man to evaluate possible malignancy of the spine revealed by MRI. The PET images revealed numerous focal FDG activity throughout the skeletal system. In addition, multiple foci of the increased activity in the mediastinal and hilar nodes were noted, suggestive of sarcoidosis, which was proven following biopsy. Therapy for sarcoidosis was initiated. In the subsequent 4 follow-up FDG PET/CT scans, the activity in both the bones and mediastinal/hilar regions fluctuated. However, anatomical abnormality in the bones on the CT images was never visualized during the entire clinical course.

  14. Clinical Manifestations, Complications and Treatment of Ocular Sarcoidosis: Correlation between Visual Efficiency and Macular Edema as Seen on Optical Coherence Tomography.

    PubMed

    Paovic, Jelena; Paovic, Predrag; Sredovic, Vojislav; Jovanovic, Svetlana

    2016-09-14

    Sarcoidosis is a chronic systemic autoimmune disease which belongs to a group of systemic granulomatous diseases. It can be confirmed through characteristic systemic and ocular manifestations and histological findings. Biopsy is the golden standard for diagnosing sarcoidosis. Ocular sarcoidosis can be confirmed, probable, or possible. Over a two-year period, ocular manifestations were studied on a sample of 52 patients, each followed for four months and diagnosed with some form of systemic sarcoidosis. Most frequent systemic manifestations in patients with ocular sarcoidosis were pulmonary, skin, glandular, and systemic generalized sarcoidosis. The disease was diagnosed four times more frequently in females than males (42:10, respectively; p < 0.05). Most frequent, and statistically significant, manifestation of ocular sarcoidosis is anterior uveitis (64.61%; p < 0.01). Macular edema and periphlebitis associated with periarteritis were frequent, and statistically significant (43.90% and 29.26%, respectively; p < 0.05). Overall, with regards to gender and location (right eye; left eye), visual acuity was >0.5 and of statistical significance (76.92%; p < 0.01). The most common therapy consisted of systemic corticosteroids (26.67%) and/or a combination of corticosteroids and immunosuppressive drugs (23.33%). In 16 eyes treated with repeated doses of sub-Tenon's injections, both initial and control visual acuity correlated with average thickness. There was positive correlation between several optical coherence tomography findings before and after treatment.

  15. Physical Activity and Chronic Prostatitis/Chronic Pelvic Pain Syndrome

    PubMed Central

    Zhang, Ran; Chomistek, Andrea K.; Dimitrakoff, Jordan D.; Giovannucci, Edward L.; Willett, Walter C.; Rosner, Bernard A.; Wu, Kana

    2014-01-01

    Purpose Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a prevalent urologic disorder among men, but its etiology is still poorly understood. Our objective was to examine the relationship between physical activity and incidence of CP/CPPS in a large cohort of male health professionals. Methods We conducted a prospective cohort study among men in the Health Professionals Follow-up Study followed from 1986 to 2008. The study population included 20,918 men who completed all CP/CPPS questions on the 2008 questionnaire. Leisure-time physical activity, including type and intensity of activity, was measured by questionnaire in 1986. A National Institute of Health Chronic Prostatitis Symptom Index pain score was calculated based on the responses on the 2008 questionnaire. Participants with pain scores ≥ 8 were considered CP/CPPS cases (n=689). Results Higher leisure-time physical activity was associated with lower risk of CP/CPPS. The multivariable-adjusted odds ratio (OR) comparing >35.0 to ≤3.5 MET-h/wk of physical activity was 0.72 (95% confidence interval (CI): 0.56, 0.92, p for trend <0.001). Observed inverse associations between physical activity and CP/CPPS were similar for both moderate- and vigorous-intensity activities. Sedentary behavior, measured as time spent watching television, was not associated with risk of CP/CPPS (p for trend 0.64). Conclusions Findings from this study, the first large scale and most comprehensive study to date on this association, suggest that higher levels of leisure-time physical activity may lower risk of CP/CPPS in middle-aged and older men. PMID:25116086

  16. Endoplasmic Reticulum Stress Is Chronically Activated in Chronic Pancreatitis*

    PubMed Central

    Sah, Raghuwansh P.; Garg, Sushil K.; Dixit, Ajay K.; Dudeja, Vikas; Dawra, Rajinder K.; Saluja, Ashok K.

    2014-01-01

    The pathogenesis of chronic pancreatitis (CP) is poorly understood. Endoplasmic reticulum (ER) stress has now been recognized as a pathogenic event in many chronic diseases. However, ER stress has not been studied in CP, although pancreatic acinar cells seem to be especially vulnerable to ER dysfunction because of their dependence on high ER volume and functionality. Here, we aim to investigate ER stress in CP, study its pathogenesis in relation to trypsinogen activation (widely regarded as the key event of pancreatitis), and explore its mechanism, time course, and downstream consequences during pancreatic injury. CP was induced in mice by repeated episodes of acute pancreatitis (AP) based on caerulein hyperstimulation. ER stress leads to activation of unfolded protein response components that were measured in CP and AP. We show sustained up-regulation of unfolded protein response components ATF4, CHOP, GRP78, and XBP1 in CP. Overexpression of GRP78 and ATF4 in human CP confirmed the experimental findings. We used novel trypsinogen-7 knock-out mice (T−/−), which lack intra-acinar trypsinogen activation, to clarify the relationship of ER stress to intra-acinar trypsinogen activation in pancreatic injury. Comparable activation of ER stress was seen in wild type and T−/− mice. Induction of ER stress occurred through pathologic calcium signaling very early in the course of pancreatic injury. Our results establish that ER stress is chronically activated in CP and is induced early in pancreatic injury through pathologic calcium signaling independent of trypsinogen activation. ER stress may be an important pathogenic mechanism in pancreatitis that needs to be explored in future studies. PMID:25077966

  17. Endoplasmic reticulum stress is chronically activated in chronic pancreatitis.

    PubMed

    Sah, Raghuwansh P; Garg, Sushil K; Dixit, Ajay K; Dudeja, Vikas; Dawra, Rajinder K; Saluja, Ashok K

    2014-10-03

    The pathogenesis of chronic pancreatitis (CP) is poorly understood. Endoplasmic reticulum (ER) stress has now been recognized as a pathogenic event in many chronic diseases. However, ER stress has not been studied in CP, although pancreatic acinar cells seem to be especially vulnerable to ER dysfunction because of their dependence on high ER volume and functionality. Here, we aim to investigate ER stress in CP, study its pathogenesis in relation to trypsinogen activation (widely regarded as the key event of pancreatitis), and explore its mechanism, time course, and downstream consequences during pancreatic injury. CP was induced in mice by repeated episodes of acute pancreatitis (AP) based on caerulein hyperstimulation. ER stress leads to activation of unfolded protein response components that were measured in CP and AP. We show sustained up-regulation of unfolded protein response components ATF4, CHOP, GRP78, and XBP1 in CP. Overexpression of GRP78 and ATF4 in human CP confirmed the experimental findings. We used novel trypsinogen-7 knock-out mice (T(-/-)), which lack intra-acinar trypsinogen activation, to clarify the relationship of ER stress to intra-acinar trypsinogen activation in pancreatic injury. Comparable activation of ER stress was seen in wild type and T(-/-) mice. Induction of ER stress occurred through pathologic calcium signaling very early in the course of pancreatic injury. Our results establish that ER stress is chronically activated in CP and is induced early in pancreatic injury through pathologic calcium signaling independent of trypsinogen activation. ER stress may be an important pathogenic mechanism in pancreatitis that needs to be explored in future studies.

  18. Decreased fibrinolytic activity in juvenile chronic arthritis.

    PubMed

    Mussoni, L; Pintucci, G; Romano, G; De Benedetti, F; Massa, M; Martini, A

    1990-12-01

    The basal fibrinolytic activity in 17 children with active juvenile chronic arthritis (JCA) was investigated. It was found that patients with JCA, and particularly those with the systemic form, show decreased plasma fibrinolytic activity and a marked increase in plasminogen activator inhibitor. Additionally, it was found that patients with systemic JCA, but not those with the polyarticular or pauciarticular form, have increased circulating levels of tissue-type plasminogen activator, and endothelial cell protein, suggesting possible endothelial cell participation in systemic JCA.

  19. Isolated muscular sarcoidosis causing fever of unknown origin: The value of gallium-67 imaging

    SciTech Connect

    Patel, N.; Krasnow, A.; Sebastian, J.L.; Collier, B.D.; Hellman, R.S.; Isitman, A.T. )

    1991-02-01

    An unusual case of a patient with a long-standing fever of unknown origin (FUO) is presented whose gallium-67 ({sup 67}Ga) images revealed increased activity only in the calf muscles bilaterally. Other imaging modalities also failed to show chest or other abnormal findings. Subsequent biopsy of the right gastrocnemius muscle revealed noncaseating granulomas consistent with the diagnosis of sarcoidosis. When using {sup 67}Ga to evaluate a patient with a FUO, imaging of the extremities should always be included. Also, when abnormal Ga-67 uptake is present in the extremities, sarcoidosis should be included in the differential diagnosis.

  20. Vertebral sarcoidosis: demonstration of bone involvement by computerized axial tomography

    SciTech Connect

    Dinerstein, S.L.; Kovarsky, J.

    1984-08-01

    A report is given of a rare case of vertebral sarcoidosis with negative conventional spinal x-ray films, yet with typical cystic lesions of the spine found incidentally during abdominal computerized axial tomography (CAT). The patient was a 28-year-old black man, who was admitted for evaluation of a 1 1/2-year history of diffuse myalgias, intermittent fever to 102 F orally, bilateral hilar adenopathy, and leukopenia. A technetium polyphosphate bone scan revealed diffuse areas of increased uptake over the sternum, entire vertebral column, and pelvis. Conventional x-ray films of the cervical, thoracic, and lumbar spine, and an AP view of the pelvis were all normal. Chest x-ray film revealed only bilateral hilar adenopathy. During the course of an extensive negative evaluation for infection, an abdominal CAT scan was done, showing multiple, small, sclerotic-rimmed cysts at multiple levels of the lower thoracic and lumbar spine. Bone marrow biopsy revealed only changes consistent with anemia of chronic disease. Mediastinal lymph node biopsy revealed noncaseating granulomas. A tentative diagnosis of sarcoidosis was made, and treatment with prednisone, isoniazid and rifampin was begun. Within two weeks of initiation of prednisone therapy, the patient was symptom-free. A repeat technetium polyphosphate bone scan revealed only a small residual area of mildly increased uptake over the upper thoracic vertebrae.

  1. Defining the clinical outcome status (COS) in sarcoidosis: results of WASOG Task Force.

    PubMed

    Baughman, R P; Nagai, S; Balter, M; Costabel, U; Drent, M; du Bois, R; Grutters, J C; Judson, M A; Lambiri, I; Lower, E E; Muller-Quernheim, J; Prasse, A; Rizzato, G; Rottoli, P; Spagnolo, P; Teirstein, A

    2011-07-01

    The clinical outcome of sarcoidosis is quite variable. Several scoring systems have been used to assess the level of disease and clinical outcome. The definition of clinical phenotypes has become an important goal as genetic studies have identified distinct genotypes associated with different clinical phenotypes. In addition, treatment strategies have been developed for patients with resolving versus non resolving disease. A task force was established by the World Association of Sarcoidosis and Other Granulomatous diseases (WASOG) to define clinical phenotypes of the disease based on the clinical outcome status (COS). The committee chose to examine patients five years after diagnosis to determine the COS. Several features of the disease were incorporated into the final nine categories of the disease. These included the current or past need for systemic therapy, the resolution of the disease, and current status of the condition. Sarcoidosis patients who were African American or older were likely to have a higher COS, indicating more chronic disease. The COS may be useful in future studies of sarcoidosis.

  2. [2 cases of sarcoidosis in Yaounde (Cameroon)].

    PubMed

    Capdevielle, P; Vauterin, G; Mouden, J C; Darie, H

    1984-01-01

    Two new cases of sarcoidosis are reported from Cameroon. The first one concerned a man, 53 years old, who presented multiple dermal nodules of the face, polyadenopathy , splenomegaly, exertional dyspnea, reticular and micronodular aspect of lungs X-ray. Diagnosis was confirmed by histology of skin, ganglions and bronchus biopsies. Patient was treated by corticotherapy. The other one concerned a woman, 28 years old, who presented successively mediastinal adenopathies, then, 9 months later, reticular and micronodular aspect of lungs X-ray. During this period, a treatment against tuberculosis had been established. Bronchus biopsies confirmed the diagnosis. The patient was also treated by corticosteroids. The authors wonder whether sarcoidosis is actually or apparently rare in Negro-Africans, owing to the fact of frequent failure to recognize this affection, or confusion with tuberculosis. Correct incidence of sarcoidosis in Negro-Africans should be defined.

  3. Pleural effusion and sarcoidosis: an unusual combination.

    PubMed

    Ferreiro, Lucía; San José, Esther; González-Barcala, Francisco Javier; Suárez-Antelo, Juan; Toubes, M Elena; Valdés, Luis

    2014-12-01

    Pleural involvement in sarcoidosis is uncommon and appears in several forms. To document the incidence and characteristics of pleural effusion in sarcoidosis patients, a review of the cases diagnosed in our centre between January 2001 and December 2012 was carried out. One hundred and ninety-five patients with sarcoidosis were identified; three (two men and one woman) presented with unilateral pleural effusion (1.5%): one in the right side and two in the left. Two were in stageii and one was in stageiv. The pleural fluid of the two patients who underwent thoracocentesis was predominantly lymphocytic. One of these patients presented chylothorax and the other had high CA-125levels. In general, these effusions are lymphocyte-rich, paucicellular, serous exudates (sometimes chylothorax) and contain proportionally higher levels of protein than LDH. Most cases are treated with corticosteroids, although it may resolve spontaneously.

  4. Sarcoidosis: a diagnostic challenge in atypical radiologic findings of unilateral lymphadenopathy

    PubMed Central

    Meillier, Andrew; Commodore, Marius

    2015-01-01

    Sarcoidosis is a chronic systemic disease with a wide array of clinical findings. Given that the clinical symptoms are not pathognomonic, chest radiographs have become essential to the initial diagnosis and choice of treatment modality. Diagnosis hinges on ruling out alternative diagnoses; sometimes, advanced radiologic techniques and histopathology are required. On this occasion, we present a case of a patient with generalized symptoms, no significant chest radiograph findings and lymphadenopathy where advanced imaging and pathology assisted in the diagnosis. PMID:26719811

  5. Development of exclusively cutaneous sarcoidosis in patient with rheumatoid arthritis during treatment with etanercept.

    PubMed

    Vieira, Marcella Amaral Horta Barbosa; Saraiva, Maria Isabel Ramos; Silva, Larissa Karine Leite da; Fraga, Rafael Cavanellas; Kakizaki, Priscila; Valente, Neusa Yuriko Sakai

    2016-11-01

    We report the case of a patient with rheumatoid arthritis who, after 2 months of treatment with etanercept, showed disseminated asymptomatic violaceous papules. Biopsy of the skin lesion showed chronic granulomatous dermatitis with negative staining for fungi and acid-fast bacilli (AFB). After discontinuation of etanercept, the patient's condition improved. Although apparently paradoxical, cases of cutaneous and systemic sarcoidosis after anti-TNF medications have been reported in the literature, with very few cases presenting exclusive cutaneous involvement.

  6. Effectiveness of infliximab in refractory FDG PET-positive sarcoidosis.

    PubMed

    Vorselaars, Adriane D M; Crommelin, Heleen A; Deneer, Vera H M; Meek, Bob; Claessen, Anke M E; Keijsers, Ruth G M; van Moorsel, Coline H M; Grutters, Jan C

    2015-07-01

    Inconclusive evidence for the efficacy of infliximab in sarcoidosis hinders the global use of this potentially beneficial drug. To study infliximab efficacy in a clinical setting, we performed a prospective open-label trial in patients refractory to conventional treatment. Patients (n=56) received eight infusions of 5 mg·kg(-1) infliximab. Pulmonary function, disease activity measured by (18)F-fluorodeoxyglucose (FDG) by positron emission tomography (PET) and quality of life were part of the clinical work-up. Infliximab levels were measured before every infusion. After 26 weeks of infliximab treatment, mean improvement in forced vital capacity (FVC) was 6.6% predicted (p=0.0007), whereas in the 6 months before start of treatment, lung function decreased. Maximum standardised uptake value (SUVmax) of pulmonary parenchyma on (18)F-FDG PET decreased by 3.93 (p<0.0001). High SUVmax of pulmonary parenchyma at baseline predicted FVC improvement (R=0.62, p=0.0004). An overall beneficial response was seen in 79% of patients and a partial response was seen in 17% of patients. No correlation between infliximab trough level (mean 18.0 µg·mL(-1)) and initial response was found. In conclusion, infliximab causes significant improvement in FVC in refractory (18)F-FDG PET positive sarcoidosis. Especially in pulmonary disease, high (18)F-FDG PET SUVmax values at treatment initiation predict clinically relevant lung function improvement. These results suggest that inclusion of (18)F-FDG PET is useful in therapeutic decision-making in complex sarcoidosis.

  7. AB042. Sarcoidosis or Berylliosis? Two diseases with similar histologic findings

    PubMed Central

    Cheva, Angeliki; Kilmpasani, Maria; Stathakis, Eustathios; Dimitriadis, Ioannis; Mpikos, Vasileios; Papaemmanouil, Styliani

    2016-01-01

    Background The case of a male patient, 71, who presented with bilateral pleural effusion and previously unknown mediastinal lymphadenopathy. Methods Resection of three left-sided paratracheal lymph nodes was performed, 0.6–1 cm in greatest diameter. The tissue material was embedded in paraffin and stained with hematoxylin-eosin. Results Two out of the three lymph nodes demonstrated a destruction of their structure, due to the presence of abundant epithelioid, non-caseating granulomas within a collagenous/sclerotic stroma. The granulomas consisted of plenty of epithelioid histiocytes and multinucleated Langhans giant-cells. Schaumann bodies and asteroid bodies were recognised. Given the above, the diagnosis was that of a granulomatous inflammatory disease, like a sarcoidosis or berylliosis. After gathering a precise patient medical history, it was revealed that he had been working for many years in fertilizer manufacturing, with chronic exposure to beryllium. Conclusions Sarcoidosis is usually a diagnosis of exclusion, as there are no pathognomonic clinical features or diagnostic examinations. When pleural effusion is the first manifestation of the disease, clinical estimation is usually oriented to other diseases. Cases have been reported, in which the patient was misdiagnosed (e.g., with tuberculosis) and mistreated for several months, before sarcoidosis is diagnosed. The microscopic examination of mediastinal lymph nodes contributes to this diagnostic challenge, with a low complications risk. Sarcoidosis and berylliosis have similar clinical, imaging and histologic findings. Typical are the epithelioid, non-caseating granulomas. Schaumann bodies are found in 70% of sarcoidosis and asteroid bodies are more unusual, found in 2–9% of the cases. For the definite differential diagnosis between these entities, a detailed medical history of the patient is necessary, while the Beryllium Lymphocyte Proliferation Test (BeLPT) is also available.

  8. Parathyroid-hormone-related protein in sarcoidosis.

    PubMed Central

    Zeimer, H. J.; Greenaway, T. M.; Slavin, J.; Hards, D. K.; Zhou, H.; Doery, J. C.; Hunter, A. N.; Duffield, A.; Martin, T. J.; Grill, V.

    1998-01-01

    Parathyroid-hormone-related protein (PTHrP) is the main mediator of the humoral hypercalcemia of malignancy. It is also detected in many normal adult and fetal tissues. Altered calcium metabolism occurs in sarcoidosis, and two cases of sarcoidosis with hypercalcemia and elevated plasma PTHrP are described. An archival study of 20 lymph node biopsies with the pathological diagnosis of sarcoidosis was performed. Immunohistochemistry using a polyclonal antiserum to human PTHrP and in situ hybridization using a riboprobe to human PTHrP were performed on the lymph node biopsies. Immunohistochemistry for PTHrP was also performed on the biopsies from the two cases with elevated plasma levels. Immunohistochemical analysis detected PTHrP in macrophages within granulomata in 17 of the 20 (85%) biopsies. In situ hybridization detected a positive signal for messenger RNA in the granulomata of 11 of 19 (58%) biopsies. PTHrP immunoreactivity and PTHrP gene expression are present in sarcoid granulomata. PTHrP may contribute to the hypercalcemia of sarcoidosis. Images Figure 1 PMID:9422518

  9. Systemic sarcoidosis mimicking malignant metastatic disease

    PubMed Central

    Hammen, Irena; Sherson, David Lee; Davidsen, Jesper Roemhild

    2015-01-01

    We present a case of systemic sarcoidosis involving the liver, pancreas, lungs, mediastinal and intraabdominal lymph nodes and bones. Multiple organ system manifestations mimicked malignant metastatic disease. The diagnosis was established with clinical, radiological, and pathological findings after neoplasm was ruled out by pathological tests. The patient showed rapid symptom remission with systemic steroid treatment. PMID:26672956

  10. Tissue Doppler imaging in cardiac sarcoidosis.

    PubMed

    Smedema, J P

    2008-07-01

    A middle-aged African lady, who presented with ventricular tachycardias, mitral valve regurgitation and congestive heart failure, was diagnosed with cardiac sarcoidosis. Tissue Doppler imaging demonstrated abnormalities suggestive of myocardial scar, which was confirmed by contrast-enhanced cardiac magnetic resonance.

  11. [Sarcoidosis of the lacrimal sac as a cause of dacriostenosis].

    PubMed

    Burduk, Paweł K; Seredyka-Burduk, Małgorzata; Kaźmierczak, Wojciech; Dalke, Krzysztof

    2013-01-01

    Sarcoidosis is a systemic granulomatous disease of unknown aetiology. The course of sarcoidosis ranges from asymptomatic to severe. It could affect people of all ages. The disease affects predominantly the lungs and lymph nodes, skin, abdominal organs or eyes. Sarcoidosis of lacrimal sac is very uncommon. We describe a young man with lacrimal sac and nasal mucosa sarcoidosis present with epiphora. Few years before the onset of dacriocystitis the patient was treated because of lymph nodes sarcoidosis. The lacrimal sac sarcoidosis developed five years after systemic disease remission. An endoscopic dacriocystorhinostomy with intubation of nasolacrimal duct was performed. We used postoperatively systemic and local steroids for 3 months period. The patient is under observation for over four years with good health. The abnormal looking nasal or lacrimal sac mucosa could be associated with granulomatous disease as sarcoidosis and Wegener's or malignancies. If the sarcoidosis is established, it could be the first manifestation of sarcoidosis leading to future systemic sarcoidosis development or it may develop many years after the onset of systemic disease. Endoscopic dacriocystorhinostomy with intubation followed by intensive therapy with systemic and local corticosteroids may be helpful to maintain lacrimal drainage patency.

  12. Sarcoidosis Blood Transcriptome Reflects Lung Inflammation and Overlaps with Tuberculosis

    PubMed Central

    Solberg, Owen D.; Peng, Jeffrey C.; Bhakta, Nirav R.; Nguyen, Christine P.; Woodruff, Prescott G.

    2011-01-01

    Rationale: Sarcoidosis is a granulomatous disease of unknown etiology, although M. tuberculosis may play a role in the pathogenesis. The traditional view holds that inflammation in sarcoidosis is compartmentalized to involved organs. Objectives: To determine whether whole blood gene expression signatures reflect inflammatory pathways in the lung in sarcoidosis and whether these signatures overlap with tuberculosis. Methods: We analyzed transcriptomic data from blood and lung biopsies in sarcoidosis and compared these profiles with blood transcriptomic data from tuberculosis and other diseases. Measurements and Main Results: Applying machine learning algorithms to blood gene expression data, we built a classifier that distinguished sarcoidosis from health in derivation and validation cohorts (92% sensitivity, 92% specificity). The most discriminative genes were confirmed by quantitative PCR and correlated with disease severity. Transcript profiles significantly induced in blood overlapped with those in lung biopsies and identified shared dominant inflammatory pathways (e.g., Type-I/II interferons). Sarcoidosis and tuberculosis shared more overlap in blood gene expression compared with other diseases using the 86-gene signature reported to be specific for tuberculosis and the sarcoidosis signature presented herein, although reapplication of machine learning algorithms could identify genes specific for sarcoidosis. Conclusions: These data indicate that blood transcriptome analysis provides a noninvasive method for identifying inflammatory pathways in sarcoidosis, that these pathways may be leveraged to complement more invasive procedures for diagnosis or assessment of disease severity, and that sarcoidosis and tuberculosis share overlap in gene regulation of specific inflammatory pathways. PMID:21852540

  13. Thoracic Sarcoidosis: Imaging with High Resolution Computed Tomography

    PubMed Central

    Singh, Sarvinder; Jain, Megha; Singh, Satyendra Narayan; Sharma, Rajat Kumar

    2017-01-01

    features of end stage lung disease on HRCT noted in a small subset of patients. HRCT was superior to chest radiography for evaluating the features, pattern and distribution of the parenchymal lesions and mediastinal lymph nodes, for assessing the stage and activity of the disease and in aiding detection of subtle parenchymal lesions which are liable to be missed on conventional imaging. Conclusion Thoracic sarcoidosis can have varied presentations. HRCT is superior to conventional CT for the detection and characterisation of the lung parenchymal lesions. PMID:28384959

  14. Complement activation in chronic liver disease.

    PubMed Central

    Munoz, L E; De Villiers, D; Markham, D; Whaley, K; Thomas, H C

    1982-01-01

    Patients with HBsAg positive chronic active liver disease (CALD) and primary biliary cirrhosis (PBC) exhibit increased C3d concentrations and changes in the serum concentrations of the complement components consistent with activation of the classical and alternative pathways. In these patients the concentrations of the regulatory proteins, C3b inactivator (C3bINA) and beta IH globulin, are normal. Patients with HBsAg negative CALD and alcohol induced liver disease (ALD) exhibit no evidence of an increased level of complement system activation. In these patients diminished serum concentrations of complement components appear to be related to diminished hepatic synthetic function. C4 synthesis may be specifically reduced in autoimmune chronic active liver disease. PMID:7083631

  15. Old-scar mass and changing surgical perspective: Sarcoidosis

    PubMed Central

    Aktimur, Recep; Aktimur, Sude Hatun; Çolak, Elif; Alıcı, Ömer; Demirağ, Mehmet Derya

    2015-01-01

    Sarcoidosis is a systemic inflammatory disease of an unknown etiology. Skin is involved in 25% of all cases, and 29% of them present as a scar sarcoidosis. Asymptomatic old-scar masses are generally regarded as a foreign body reaction by surgeons and often result in excisional biopsy. We describe a case of a patient who developed sarcoidosis in a 34-year-old appendectomy scar and adjacent inguinal lymph nodes without any local or systemic symptom and radiologic finding. Surgeons should not underestimate the importance of such lesions as a simple condition. Scar sarcoidosis may resolve spontaneously, or the treatment with some topical agents is effective. Furthermore, scar sarcoidosis may be the initial manifestation of systemic sarcoidosis. PMID:25931946

  16. Etiology of Sarcoidosis: Does Infection Play a Role?

    PubMed Central

    Saidha, Shiv; Sotirchos, Elias S.; Eckstein, Christopher

    2012-01-01

    Sarcoidosis is a granulomatous inflammatory disorder of unclear etiology, which is known to affect multiple organ systems including the lungs, heart, skin, central nervous system, and eyes, among others. For this reason, sarcoidosis represents a systemic medical disorder that is clinically relevant to multiple medical sub-specialties. Despite extensive research, the etiology of sarcoidosis has yet to be elucidated, although most evidence supports that the pathogenetic mechanism of sarcoidosis is an aberrant immune response, driven by an unidentified antigen (or antigens) in genetically susceptible individuals. Multiple candidate etiologic agents, including microbial organisms and environmental agents, have been investigated, but study results are inconclusive. In this review, we describe the known histologic and immunologic features of sarcoidosis and discuss the evidence supporting a role for infectious processes in the pathogenesis of sarcoidosis. PMID:22461752

  17. [Sarcoidosis presenting with Raynaud's syndrome: a case report].

    PubMed

    Nigro, A; Iannone, F; Grattagliano, V; Sanguedolce, F; Lapadula, G

    2004-01-01

    We report a case of association between sarcoidosis and Raynaud's syndrome. A 39 year old female presented fatigue, Raynaud's syndrome, IgG and erithrosedimentation rate (ESR) increase, polyarthralgy in which disseminated micronodular infiltration in the chest X-ray and histological demonstration of non-caseating epitheloid microgranulomas led to a diagnosis of concomitant sarcoidosis. Clues to the diagnosis of sarcoidosis coexisting with autoimmune disease are discussed.

  18. Sarcoidosis presenting as isolated gingival enlargement: a rare case entity.

    PubMed

    Tripathi, Pragya; Aggarwal, Jaihans; Chopra, Deepak; Bagga, Sukhchain; Sethi, Kanika

    2014-11-01

    Sarcoidosis is a non-caseating granulomatous disease . It is a multiorgan inflammatory disorder of unknown etiology. Conditions affecting skin or other organs frequently involve oral cavity and rarely manifest as gingival disease. Here we are reporting a rare case in which gingival hyperplasia was the initial symptom which finally led to the diagnosis of sarcoidosis. Oral mucous membrane needs to be examined carefully as it may constitute in presenting first sign of systemic sarcoidosis.

  19. Venous Leg Ulcer in a Sarcoidosis Patient: A Case Report

    PubMed Central

    Ohn, Jungyoon; Byun, Sang Young; Kim, In Su

    2015-01-01

    Venous leg ulcers, the most common form of leg ulcers, are relevant to the pathogenicity of pericapillary fibrin cuff. Sarcoidosis, a multiorgan granulomatous disease, causes fibrin deposition in tissues. We report a case of a 50-year-old man with venous leg ulcers coexisting with sarcoidosis. On the basis of the histologic findings, we propose the hypothesis that sarcoidosis patients are prone to the development of venous leg ulcers. PMID:26719645

  20. Evidence-based therapy for cutaneous sarcoidosis.

    PubMed

    Doherty, Christy B; Rosen, Ted

    2008-01-01

    Although healthcare providers have arrived at a relatively comfortable zone of accepted clinical practice in the management of cutaneous sarcoidosis, virtually every treatment is based on minimal evidence-based data and relies almost exclusively on anecdotal information. Although it would be convenient to blame this state of affairs on the lack of certainty about disease aetiology, the unavoidable fact is that little has been executed, even in the realm of well designed comparative trials. Nonetheless, worldwide accepted standard therapies for sarcoidosis include the administration of corticosteroids, antimalarials and methotrexate. A stepwise approach to patient care is appropriate, and potent topical corticosteroids (e.g. clobetasol) or repeated intralesional injections of triamcinolone (3-10 mg/mL) may be all that is needed in mild skin-limited disease. In patients requiring systemic therapy for recalcitrant or deforming skin lesions (or for widespread disease), corticosteroids (e.g. prednisone 40-80 mg/day, tapered accordingly) used alone or in combination with antimalarials or methotrexate may be indicated. Antimalarials and methotrexate are considered second-line interventions and may be used as monotherapy for steroid-resistant sarcoidosis or in patients unable to tolerate steroids. Given the concern regarding ocular toxicity, the maximum dosages of chloroquine and hydroxychloroquine should not exceed 3.5 and 6.5 mg/kg/day, respectively. Methotrexate is given in weekly doses of 10-30 mg, with the caveat that haematological, gastrointestinal, pulmonary and hepatic toxicities are possible. Despite universal acceptance as standard care, the aforementioned treatments often result in an incomplete clinical response or unacceptable adverse events. In such situations, more innovative treatment options may be used. Treatments that may well gain widespread future use include the tumour necrosis factor-alpha inhibitors infliximab and adalimumab. Experience is limited

  1. Unsuspected exposure to beryllium: potential implications for sarcoidosis diagnoses.

    PubMed

    Laczniak, Andrew N; Gross, Nathan A; Fuortes, Laurence J; Field, R William

    2014-07-21

    Exposure to Beryllium (Be) can cause sensitization (BeS) and chronic beryllium disease (CBD) in some individuals.  Even relatively low exposures may be sufficient to generate an asymptomatic, or in some cases a symptomatic, immune response. Since the clinical presentation of CBD is similar to that of sarcoidosis, it is helpful to have information on exposure to beryllium in order to reduce misdiagnosis. The purpose of this pilot study is to explore the occurrence of Be surface deposits at worksites with little or no previous reported use of commercially available Be products.  The workplaces chosen for this study represent a convenience sample of businesses in eastern Iowa. One hundred thirty-six surface dust samples were collected from 27 businesses for analysis of Be. The results were then divided into categories by the amount of detected Be according to U.S. Department of Energy guidelines as described in 10 CFR 850.30 and 10 CFR 850.31. Overall, at least one of the samples at 78% of the work sites tested contained deposited Be above the analytical limit of quantitation (0.035 µg beryllium per sample).  Beryllium was detected in 46% of the samples collected. Twelve percent of the samples exceeded 0.2 µg/100 cm² and 4% of the samples exceeded a Be concentration of 3 µg/100 cm². The findings from this study suggest that there may be a wider range and greater number of work environments that have the potential for Be exposure than has been documented previously.  These findings could have implications for the accurate diagnosis of sarcoidosis.

  2. Gene-environment interactions in sarcoidosis

    PubMed Central

    Culver, Daniel A.; Newman, Lee S.; Kavuru, Mani S.

    2007-01-01

    Susceptibility to most human diseases is polygenic, with complex interactions between functional polymorphisms of single genes governing disease incidence, phenotype, or both. In this context, the contribution of any discrete gene is generally modest for a single individual, but may confer substantial attributable risk on a population level. Environmental exposure can modify the effects of a polymorphism, either by providing a necessary substrate for development of human disease or because the effects of a given exposure modulate the effects of the gene. In several diseases, genetic polymorphisms have been shown to be context-dependent, i.e. the effects of a genetic variant are realized only in the setting of a relevant exposure. Since sarcoidosis susceptibility is dependent on both genetic and environmental modifiers, the study of gene-environment interactions may yield important pathogenetic information and will likely be crucial for uncovering the range of genetic susceptibility loci. However, the complexity of these relationships implies that investigations of gene-environment interactions will require the study of large cohorts with carefully-defined exposures and similar clinical phenotypes. A general principle is that the study of gene-environment interactions requires a sample size at least several-fold greater than for either factor alone. To date, the presence of environmental modifiers has been demonstrated for one sarcoidosis susceptibility locus, HLA-DQB1, in African-American families. This article reviews general considerations obtaining for the study of gene-environment interactions in sarcoidosis. It also describes the limited current understanding of the role of environmental influences on sarcoidosis susceptibility genes. PMID:17560304

  3. Coexistent Sarcoidosis and Tuberculosis: A Case Report.

    PubMed

    Carbonelli, Cristiano; Giuffreda, Ernesto; Palmiotti, Antonio; Loizzi, Domenico; Lococo, Filippo; Carpagnano, Elisiana; Lacedonia, Donato; Sollitto, Francesco; Foschino, Maria Pia

    2017-02-09

    Necrotizing granulomatous diseases of the lungs are usually dependent on a narrow range of differential diagnoses. Tuberculosis (TB) is responsible for the largest number of cases, while necrotizing sarcoidosis is generally considered a rare and easily distinguishable disease substantially based on histological features. However, this entity has become a viable diagnosis in the absence of mycobacteria isolation or when a remarkable clinical improvement cannot be achieved with the combination of anti-TB drugs at full dosage. The classic manifestations of TB and sarcoidosis have an overlapping range for which it is sometimes difficult to make a clinical diagnosis. Furthermore, the role of mycobacteria as a trigger antigen capable of evoking the clinical expression of sarcoidosis is a hypothesis supported by evidence from some cases. We report a case of bilateral tuberculous pleurisy in a 45-year-old male native of a North-African region with an atypical severe multisystem disease characterized by a fever resistant to anti-TB therapy and respondent to corticosteroid treatment. The choice to continue both steroid and anti-TB therapy proved to be correct for the late evidence of TB mycobacterial growth only on pleural specimens. The case described is suggestive of a coexistent systemic sarcoid manifestation and low-antigen TB, which is an underrecognized entity in the medical literature.

  4. [Morpheiform sarcoidosis as atypical manifestation of sarcoidosis. Review of the literature and differential diagnosis].

    PubMed

    Castellanos-González, María; Picazo Talavera, María Remedios

    2016-09-16

    Sarcoidosis is an idiopathic multisystem granulomatous disease that commonly involves the skin in 25% of affected patients. Because lesions assume a vast array of morphologies, a classification dividing them into specific (with presence of typical granulomas in the biopsy) or nonspecific (not containing granulomas) has been proposed. In the first group the variant morpheaform is considered exceptional. We review the cases reported in the literature and describe the possible differential diagnosis. We highlight the importance of recognizing the very atypical presentation of sarcoidosis and its ability to mimic morpheaform or sclerosis diseases in our patients.

  5. Cryptococcal meningitis in an HIV negative patient with systemic sarcoidosis.

    PubMed Central

    Botha, R J; Wessels, E

    1999-01-01

    A case of Cryptococcus neoformans meningitis is described in an HIV negative patient with undiagnosed systemic sarcoidosis. The patient presented with signs of meningitis together with generalised lymphadenopathy and hepatosplenomegaly. Cryptococcal meningitis was diagnosed on lumbar puncture. She was treated with intravenous amphotericin B but died within two weeks of admission. Necropsy revealed lesions in the lungs, liver, spleen, lymph nodes, small intestine, and bone marrow consistent with sarcoidosis. Microscopically the lesions contained non-caseating epithelioid cell granulomas typical of sarcoidosis. No Schaumann or Hamazaki-Wesenberg bodies were identified. Cryptococcus neoformans meningitis is generally associated with immunosuppressive disorders. As T cell abnormalities have been described in sarcoidosis, this could have been a case of opportunistic infection. Although rare, sarcoidosis merits consideration in patients with cryptococcal disease in the absence of HIV infection. Images PMID:10711260

  6. Recognition of distinctive patterns of gallium-67 distribution in sarcoidosis

    SciTech Connect

    Sulavik, S.B.; Spencer, R.P.; Weed, D.A.; Shapiro, H.R.; Shiue, S.T.; Castriotta, R.J. )

    1990-12-01

    Assessment of gallium-67 ({sup 67}Ga) uptake in the salivary and lacrimal glands and intrathoracic lymph nodes was made in 605 consecutive patients including 65 with sarcoidosis. A distinctive intrathoracic lymph node {sup 67}Ga uptake pattern, resembling the Greek letter lambda, was observed only in sarcoidosis (72%). Symmetrical lacrimal gland and parotid gland {sup 67}Ga uptake (panda appearance) was noted in 79% of sarcoidosis patients. A simultaneous lambda and panda pattern (62%) or a panda appearance with radiographic bilateral, symmetrical, hilar lymphadenopathy (6%) was present only in sarcoidosis patients. The presence of either of these patterns was particularly prevalent in roentgen Stages I (80%) or II (74%). We conclude that simultaneous (a) lambda and panda images, or (b) a panda image with bilateral symmetrical hilar lymphadenopathy on chest X-ray represent distinctive patterns which are highly specific for sarcoidosis, and may obviate the need for invasive diagnostic procedures.

  7. Pulmonary sarcoidosis: An important differential diagnosis in transbronchial lung biopsies

    PubMed Central

    Mahapatra, Qury S.; Sahai, Kavita; Rathi, K. R.; Singh, Sarvinder; Sharma, Shruti

    2014-01-01

    Background: Sarcoidosis is a systemic granulomatous disease of unknown etiology. Lungs and lymphatics are the principal sites affected by this disease. The disorder is often not suspected by physicians. Materials and Methods: This was a retrospective study done on 140 transbronchial lung biopsies received for histopathological examination in the Department of Pathology for 1 year in a multispeciality tertiary care hospital, in Delhi. Results: Out of 140 transbronchial lung biopsies studied, 13 cases of sarcoidosis were diagnosed histopathologically. In these patients a clinical, pathological, and radiological corelation was done. And a final diagnosis of sarcoidosis was given after excluding other granulomatous lesions. Conclusion: Transbronchial lung biopsies have become an important tool in the diagnosis of sarcoidosis in present time. Hence sarcoidosis should be considered as a differential diagnosis when dealing with granulomatous lesions in lung biopsies. PMID:24778476

  8. Diagnosis of sarcoidosis from a biopsy of a dilated mammary duct.

    PubMed

    Mason, Callan; Yang, Robert; Hamilton, Raynal; Punar, Metin; Shah, Zeeshan; Spigel, Joseph; Wang, Jean

    2017-04-01

    Sarcoidosis is an immunologic disease of unknown etiology that manifests most frequently within the lungs or associated lymph nodes. Sarcoidosis involving the breast is seen in <1% of cases and usually is diagnosed in patients with multisystem disease. The clinical and imaging presentations of sarcoidosis of the breast can be variable. Though uncommon, sarcoidosis should be considered in the differential diagnosis of a breast lesion, and given that imaging characteristics cannot distinguish between sarcoidosis and malignancy, all breast lesions in patients with sarcoidosis should be biopsied. Our case study demonstrates a diagnosis of sarcoidosis in an asymptomatic patient presenting with a single dilated duct and associated filling defect within the right breast.

  9. Diagnosis of sarcoidosis from a biopsy of a dilated mammary duct

    PubMed Central

    Yang, Robert; Hamilton, Raynal; Punar, Metin; Shah, Zeeshan; Spigel, Joseph; Wang, Jean

    2017-01-01

    Sarcoidosis is an immunologic disease of unknown etiology that manifests most frequently within the lungs or associated lymph nodes. Sarcoidosis involving the breast is seen in <1% of cases and usually is diagnosed in patients with multisystem disease. The clinical and imaging presentations of sarcoidosis of the breast can be variable. Though uncommon, sarcoidosis should be considered in the differential diagnosis of a breast lesion, and given that imaging characteristics cannot distinguish between sarcoidosis and malignancy, all breast lesions in patients with sarcoidosis should be biopsied. Our case study demonstrates a diagnosis of sarcoidosis in an asymptomatic patient presenting with a single dilated duct and associated filling defect within the right breast.

  10. Dual Analysis for Mycobacteria and Propionibacteria in Sarcoidosis BAL

    PubMed Central

    Oswald-Richter, Kyra A.; Beachboard, Dia C.; Seeley, Erin H.; Abraham, Susamma; Shepherd, Bryan E.; Jenkins, Cathy A.; Culver, Daniel A.; Caprioli, Richard M.; Drake, Wonder P.

    2012-01-01

    Purpose Sarcoidosis is a non-caseating granulomatous disease for which a role for infectious antigens continues to strengthen. Recent studies have reported molecular evidence of mycobacteria or propionibacteria. We assessed for immune responses against mycobacterial and propionibacterial antigens in sarcoidosis bronchoalveolar lavage (BAL) using flow cytometry, and localized signals consistent with microbial antigens with sarcoidosis specimens, using matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS). Methods BAL cells from 27 sarcoidosis, 14 PPD- controls, and 9 subjects with nontuberculosis mycobacterial (NTM) infections were analyzed for production of IFN-γ after stimulation with mycobacterial ESAT-6 and Propionibacterium acnes proteins. To complement the immunological data, MALDI-IMS was performed to localize ESAT-6 and Propionibacterium acnes signals within sarcoidosis and control specimens. Results CD4+ immunologic analysis for mycobacteria was positive in 17/27 sarcoidosis subjects, compared to 2/14 PPD-subjects, and 5/9 NTM subjects (p=00.008 and p=00.71 respectively, Fisher's exact test). There was no significant difference for recognition of P. acnes, which occurred only in sarcoidosis subjects that also recognized ESAT-6. Similar results were also observed for the CD8+ immunologic analysis. MALDI-IMS localized signals consistent with ESAT-6 only within sites of granulomatous inflammation, whereas P. acnes signals were distributed throughout the specimen. Conclusions MALDI-IMS localizes signals consistent with ESAT-6 to sarcoidosis granulomas, whereas no specific localization of P. acnes signals is detected. Immune responses against both mycobacterial and P. acnes are present within sarcoidosis BAL, but only mycobacterial signals are distinct from disease controls. These immunologic and molecular investigations support further investigation of the microbial community within sarcoidosis granulomas. PMID:22552860

  11. Risk of cardiovascular disease among patients with sarcoidosis: a population-based retrospective cohort study, 1976-2013.

    PubMed

    Ungprasert, Patompong; Crowson, Cynthia S; Matteson, Eric L

    2017-02-01

    A higher incidence of cardiovascular disease (CVD) has been observed in several chronic inflammatory diseases. However, data on sarcoidosis are limited.In this study, 345 patients with incident sarcoidosis in Olmsted County (Minnesota, USA) during 1976-2013 were identified based on comprehensive medical record review. 345 sex- and age-matched comparators were also identified from the same underlying population. Medical records were individually reviewed for CVD, including coronary artery disease, congestive heart failure, atrial fibrillation, cerebrovascular accident, transient ischaemic attack, peripheral arterial disease and abdominal aortic aneurysm. Cox proportional hazards models with adjustment for age, sex, calendar year and cardiovascular risk factors were used to compare the rate of development of CVD between cases and comparators.The prevalence of CVD before the index date was not significantly different between the two groups. Adjusting for age, sex and calendar year, the risk of incident CVD after the index date was significantly elevated among patients with sarcoidosis with an adjusted hazard ratio of 1.57 (95% CI 1.15-2.16). Adjustment for cardiovascular risk factors yielded an adjusted hazard ratio of 1.65 (95% CI 1.08-2.53). Significantly increased risk was also observed for several types of CVD, including coronary artery disease, congestive heart failure, atrial fibrillation and cerebrovascular accident.Increased incidence of CVD among patients with sarcoidosis was demonstrated in this population-based cohort, even after controlling for baseline traditional atherosclerotic risk factors.

  12. Fungal exposure in homes of patients with sarcoidosis - an environmental exposure study

    PubMed Central

    2011-01-01

    Background There is increasing evidence that exposure to moulds (fungi) may influence the development of sarcoidosis. To assess the influence of the environmental exposure, a study was undertaken to determine the exposure to fungi in homes of subjects with sarcoidosis. Methods Subjects were patients with clinically established sarcoidosis recruited during the period September 2007 till June 2010. Of these 55 were newly diagnosed and currently under treatment for less than one year, 25 had been treated and had no recurrence and 27 had been treated but had recurrence of the disease. Controls were healthy subjects without any respiratory symptoms (n = 30). Samples of air (about 2.5 m3) were taken in the bedroom of the subjects using a portable pump and cellulose ester filters. The filters were analysed for the content of the enzyme N-acetylhexosaminidase (NAHA) as a marker of fungal cell biomass, using a specific substrate and a fluorescent technique and expressed as NAHA units (U)/m3. Results Compared to controls, subjects undergoing treatment of the disease (newly diagnosed or with recurrence) had significantly higher activities of NAHA in their homes than controls (33.6 and 39.9 vs 10.0 U/m3, p < 0.001 and <0.001). Among controls only 5 out of 30 subjects had levels of NAHA above the second quartile value (14 U/m3). In homes of subjects with newly diagnosed disease with treatment less than one year, values above 14 NAHA U/m3 were found among 35 out of 55 and among those with recurrent disease among 18 out of 27. Conclusions The higher activities of NAHA enzyme found in homes of subjects with active and recurrent sarcoidosis suggest that exposure to fungi is related to the risk of sarcoidosis. Further environmental studies to assess the importance of this exposure for subjects with sarcoidosis are warranted. The results suggest that remedial actions in homes with high levels of fungi may be justified. PMID:21251285

  13. FDG PET/CT Evidence of Effective Treatment of Cardiac Sarcoidosis With Adalimumab.

    PubMed

    Miller, Christina T; Sweiss, Nadera J; Lu, Yang

    2016-05-01

    A 53-year-old man with mediastinal lymph node biopsy and cardiac MRI-proven cardiac sarcoidosis (CS) received treatment with pacemaker and steroids. FDG PET/CT showed active CS despite treatment with prednisone and methotrexate. Addition of weekly adalimumab (Humira) injections was introduced for 3 months. Follow-up FDG PET/CT showed complete resolution of CS as well as improvement of other sarcoid lesions in the thoracic lymph nodes.

  14. Plasma catecholamine activity in chronic lead poisoning

    SciTech Connect

    deCastro, F.J.

    1990-04-01

    Plasma catecholamines where measured in 15 children with chronic lead poisoning and 15 matched controls by radioimmunassay. The data suggest that plasma catecholamines (norepinephrine and epinphrine) were significantly elevated in chronic lead poisoning. Plasma catecholamine elevation may well be important in the clinical finding of hyperactivity and hypertension associated with chronic lead poisoning.

  15. A Rare Presentation of Sarcoidosis as a Pancreatic Head Mass

    PubMed Central

    Mony, Shruti; Patil, Pradnya D.; English, Rebekah; Das, Ananya; Culver, Daniel A.

    2017-01-01

    Sarcoidosis is a multisystem granulomatous syndrome of unknown etiology with noncaseating epithelioid granulomas being the pathognomonic pathological finding. Sarcoidosis most commonly involves the lungs and involvement of the gastrointestinal (GI) tract is uncommon. Pancreatic sarcoidosis is very rare, especially when it is the presenting feature of sarcoidosis and can masquerade as pancreatic cancer. Tissue infiltration in pancreatic sarcoidosis can lead to either a diffuse nodular appearance or a mass-like lesion. We present an interesting case of a 47-year-old woman with a 10-pack-year history of smoking who presented with sharp epigastric pain, weight loss, and elevated lipase level. CT and MRI imaging showed a 4 cm × 5 cm heterogeneous pancreatic mass with a dilated pancreatic duct and peripancreatic lymphadenopathy. Endoscopic ultrasound guided FNA revealed noncaseating granulomas with no evidence of malignancy or atypical infection. CT of the chest revealed bilateral mediastinal and hilar adenopathy with calcification, without any parenchymal abnormalities, and her angiotensin-converting enzyme level was elevated at 170 U/L. The clinical picture pointed to the diagnosis of pancreatic sarcoidosis. Given the severity of gastrointestinal symptoms related to pancreatic sarcoidosis, prednisone therapy at 0.5 mg/kg/day was initiated with complete resolution of symptoms at 8 weeks. PMID:28321355

  16. A rare presentation of sarcoidosis with nasal bone involvement

    PubMed Central

    Uslu, Selen; Korkmaz, Hakan; Çetinkol, Yeliz

    2016-01-01

    Background: Sarcoidosis is a multisystem granulomatous inflammatory disease that is induced by infectious or noninfectious environmental antigens in a genetically susceptible host. Tuberculosis and sarcoidosis are two diseases with similar clinical and pathologic findings. The link between these two diseases has been extensively studied. Objective: Herein we describe a case of sarcoidosis associated with tuberculosis, treated for tuberculosis, and, 1 year, later presented with a nasal dorsal lump and skin lesions on the extremities. Methods: Case report with clinical description. Results: Our patient had a history of skin and cervical lymphadenopathy symptoms 1 year earlier and was treated with antituberculosis drugs in an outer medical center. Therapy had cured cervical lymphadenopathies, with no improvement in skin lesions. On appearance of the nasal dorsal lump, she presented to our outpatient clinic. We retrieved the previous specimens of the patient, which revealed coexistence of necrotizing granulomas with non-necrotizing granulomas, which was strongly indicative of the coexistence of tuberculosis and sarcoidosis. Radiologic, histopathologic, and microbiologic investigation revealed the diagnosis of sarcoidosis with nasal, cutaneous, and pulmonary involvement. Treatment with prednisolone and hydroxychloroquine resulted in dramatic improvement of nasal bone, pulmonary, and skin lesions within 2 weeks. Conclusion: The clinical presentation of sarcoidosis can be complex, and the differential diagnosis from tuberculosis can be challenging. Atypical clinical pictures also can cause delays in diagnosis and proper management. In patients with granulomatous lesions that are unresponsive to antituberculosis therapy, physicians must be alerted to the possibility of coexistent sarcoidosis. PMID:27103561

  17. Prolidase activity in chronic plaque psoriasis patients

    PubMed Central

    Aksoy, Nurten; Ozgöztas, Orhan; Sezen, Hatice; Yesilova, Yavuz; Turan, Enver

    2015-01-01

    Introduction Psoriasis is a chronic, inflammatory, T-cell-mediated and hyperproliferative skin disease characterized by erythematous, squamous, sharply circumscribed and infiltrated plaques. The metabolisms of the collagen proteins undergo considerable changes due to the acceleration of their turnovers as a result of increased prolidase activity in psoriasis patients. Aim To determine the level of prolidase activity in psoriasis patients and evaluate its relationship with the oxidative system. Material and methods The serum prolidase enzyme activity, total antioxidant levels and total oxidant levels of 40 psoriasis patients and a control group including 47 healthy individuals were analyzed by using their serum samples, and their oxidative stress indices were calculated. Results The prolidase levels (p < 0.01), total oxidant levels (p < 0.01) and oxidative stress index levels (p < 0.001) of the patient group were higher than the corresponding parameters in the control group. The total antioxidant level was low (p < 0.01). Although a positive correlation was found between the prolidase and total antioxidant levels and the total oxidant level, no correlation was found between prolidase and the oxidative stress index. Conclusions It has been determined that the activity of the prolidase enzyme increases due to the increased collage turnover in psoriasis patients. Increased serum oxidant levels and oxidative stress indices values may play a role in the pathogenesis of psoriasis. PMID:26015776

  18. [Necrotizing systemic sarcoidosis with pulmonary and central nervous system involvement].

    PubMed

    Ríos Fernández, R; Callejas-Rubio, J L; Guerrero Fernández, M; Serrano Falcón, M M; Ortego-Centeno, N

    2008-01-01

    Sarcoidosis is a multisystemic disease which diagnosis depends on the presence of nonnecrotizing granulomas in the biopsy. However there are variants such as necrotizing sarcoidal granulomas or nodular sarcoidosis which have atypical findings and make difficult the differential diagnosis with other infectious processes. We describe a case of a man who develops granulomas with extensive necrosis in a systemic sarcoidosis that affected the lung and the central nervous system. This finding made us to make the diagnosis of tuberculosis and delay the specific treatment.

  19. Unmasking sarcoidosis following surgery for Cushing disease

    PubMed Central

    Diernaes, Jon E.F.; Bygum, Anette; Poulsen, Per L.

    2016-01-01

    ABSTRACT We present a patient with Cushing disease apparently suppressing sarcoidosis, which was unmasked following surgical resection of a pituitary adrenocorticotropin (ACTH)-producing microadenoma. Case report and a short review of the literature published in this area. A 46-year-old Caucasian woman presented with symptoms of hypercortisolism such as progressive weight gain, Cushingoid appearance, proximal myopathy, easy bruising, and amenorrhea. Blood testing including inferior petrosal sinus sampling uncovered an ACTH-producing microadenoma in the right aspect of the anterior pituitary gland for which the patient underwent transphenoidal resection. Maintenance corticosteroid therapy was implemented, and the signs and symptoms of Cushing disease began to resolve. Three months after surgery, multiple erythematous painful nodules developed on the patient's arms. Erythema nodosum (EN) was diagnosed clinically and a suspicion of underlying sarcoidosis was substantiated by lung imaging and elevated plasma interleukin (IL)-2 receptor. One month later, the lesions spontaneously resolved without therapy other than maintenance glucocorticoid replacement. Physicians should be aware that patients undergoing successful treatment of Cushing syndrome may have a flare-up or emergence of a corticosteroid-responsive disease. PMID:27375832

  20. ProKaSaRe Study Protocol: A Prospective Multicenter Study of Pulmonary Rehabilitation of Patients With Sarcoidosis

    PubMed Central

    Lingner, Heidrun; Großhennig, Anika; Flunkert, Kathrin; Buhr-Schinner, Heike; Heitmann, Rolf; Tönnesmann, Ulrich; van der Meyden, Jochen

    2015-01-01

    Background Available data assessing the efficacy of pulmonary rehabilitation for patients with chronic sarcoidosis are scant; for Germany, there are none at all. Objective To gain information about the benefit of in-house pulmonary rehabilitation for patients with chronic sarcoidosis and for the health care system, we intend to collect data in a prospective multicenter “real-life” cohort trial. Methods ProKaSaRe (Prospektive Katamnesestudie Sarkoidose in der pneumologischen Rehabilitation) [Prospective Catamnesis Study of Sarcoidosis in Pulmonary Rehabilitation] will assess a multimodal 3-week inpatient pulmonary rehabilitation program for adult patients with chronic sarcoidosis over a 1-year follow-up time. Defined specific clinical measurements and tests will be performed at the beginning and the end of the rehabilitation. In addition, questionnaires concerning health-related quality of life and the patients’ symptoms will be provided to all patients. Inclusion criteria will be referral to one of the 6 participating pulmonary rehabilitation clinics in Germany for sarcoidosis and age between 18 and 80 years. Patients will only be excluded for a lack of German language skills or the inability to understand and complete the study questionnaires. To rule out seasonal influences, the recruitment will take place over a period of 1 year. In total, at least 121 patients are planned to be included. A descriptive statistical analysis of the data will be performed, including multivariate analyses. The primary outcomes are specific health-related quality of life (St George’s Respiratory Questionnaire) and exercise capacity (6-minute walk test). The secondary outcomes are several routine lung function and laboratory parameters, dyspnea scores and blood gas analysis at rest and during exercise, changes in fatigue, psychological burden, and generic health-related quality of life (36-item Short Form Health Survey). Results Funding was obtained on October 12, 2010

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

    PubMed Central

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

    2016-01-01

    It has been reported that oscillatory gamma activity participates in brief acute pain and tonic ongoing pain. It is of great interest to determine whether the gamma activity is involved in chronic pain since chronic pain is a more severe pathological condition characterized by pain persistency. To investigate the oscillatory gamma activity in chronic pain, in the present study, we recorded spontaneous electrocorticogram (ECoG) signals during chronic pain development in rats with chronic inflammatory pain induced by monoarthritis. Power spectrum analysis of ECoG data showed that gamma power increased significantly at the late stage of chronic inflammatory pain. The increased gamma activity occurred mainly at electrodes over primary somatosensory cortices. In rats with chronic pain, the gamma power was positively correlated with the hyperalgesia measured by laser energy that elicited hindpaw withdrawal response. Furthermore, an increased coupling between the amplitude of gamma power and the phase of theta oscillations was observed in chronic inflammatory pain condition. These results indicate an enhanced spontaneous gamma activity in chronic pain and suggest a potential biomarker for the severity of chronic pain. PMID:27847461

  2. Sarcoidosis of the skin: a review for the pulmonologist.

    PubMed

    Lodha, Saurabh; Sanchez, Miguel; Prystowsky, Stephen

    2009-08-01

    With vastly heterogeneous morphologic manifestations, sarcoidosis is one of the "great imitators" of medicine. Because there is no specific confirmatory test, the diagnosis rests on clinical acumen coupled with supportive information from tissue or blood evaluation and the exclusion of other diseases. The characteristic histologic pattern of noncaseating, epithelioid cell granulomas is not always present in skin lesions, which may be visually distinctive or diverse in appearance. As a result of their high incidence of respiratory disease, patients with sarcoidosis frequently seek care from pulmonologists who may become their primary health-care providers. Physicians who treat patients with sarcoidosis should be aware of the disease's diverse organ manifestations, but particularly those appearing on the skin because these can be disfiguring, have prognostic importance, and may not be readily diagnosed even by skin specialists. In this comprehensive review, we sought to illustrate this diversity and to update the diagnostic approach, histologic spectrum, and therapeutic strategies involved in cutaneous sarcoidosis.

  3. An Isolated Mass in the Palm, Starting Manifestation of Sarcoidosis

    PubMed Central

    Ghorbanhoseini, Mohammad; Yazdi, Hamidreza; Naseh, Hossein; Hafezi, Poopak

    2016-01-01

    Sarcoidosis is a systemic disease that is characterized with noncaseating granulomatous nodules which present in multiple organs specially lungs (90%). Incidence of masses due to Sarcoidosis in upper extremity is low and most cases present in association with involvement of pulmonary hilary lymph nodes. In this article we present a rare case of Sarcoidosis which presented as a single soft tissue mass in hand without osseous or pulmonary hillary lymph node involvement. Incidence of involvement of musculoskeletal system is 1-5 %, mostly it occurs in small bones in hands and feet. In most cases involvement of soft tissue in extremities is accompanied with bone lesions. Those cases of soft tissue involvement are generally coincide with pulmonary lymph nodules. To the authors` knowledge, this is the first case of Sarcoidosis that presents without spreading in bones or pulmonary hilar lymph nodes. PMID:26894226

  4. Isolated cutaneous sarcoidosis: a new insight into the old entity.

    PubMed

    Kumar H K, Sharath; M N, Gayathri; M, Bharathi; T, Ravikumar

    2013-08-01

    Cutaneous lesions are a part of common manifestation in multi-systemic sarcoidosis and skin involvement occurs in 20% to 35% of the patients with systemic disease. An exclusive cutaneous involvement is rare and it is reported in about 4%-5% of the patients of sarcoidosis. These lesions have been classified into specific and non-specific, depending on the presence of non- caseating granulomas, on histopathologic studies. In the present study, we are reporting two cases of isolated cutaneous sarcoidosis without systemic manifestations, which is a rare presentation. Sarcoidosis will continue to challenge even the most experienced clinicians with respect to a high degree of suspicion and further investigations for diagnosing and treating this disorder.

  5. Concomitant axillary mycobacteriosis and neuro-sarcoidosis: diagnostic pitfalls

    PubMed Central

    Meckenstock, Roderich; Therby, Audrey; Chapelon-Abric, Catherine; Nifle, Chantal; Beressi, Jean Paul; Lebas, Constance; Greder–Belan, Alix

    2011-01-01

    There are many similarities between mycobacteriosis, in particular, tuberculosis, and sarcoidosis such as predominant intrathoracic localisation (even if all organs and tissues may be concerned), great variability of phenotypic expression, and granulomatous inflammatory reaction, caseous necrosis not being an absolute criterion of tuberculosis. Moreover, microbial (or mycobacterial?) agents may play a role in the pathogenesis of sarcoidosis which remains a diagnosis of exclusion particularly in atypical cases. The authors report a case of a non-immunocompromised female patient who presented, simultaneously, isolated axillary tubercular adenitis and neuro-sarcoidosis without any other localisation. This case illustrates the difficulty to distinguish between both of these two diseases and thus to choose an adequate treatment when diagnosis is not proven. Moreover, our patient (human leucocyte antigen B27 positive) presented symptoms of spondylarthritis which also may have a nosological link with tuberculosis or sarcoidosis. PMID:22679226

  6. Sarcoidosis and primary biliary cirrhosis with co-existing myositis

    PubMed Central

    Hughes, P.; McGavin, C. R.

    1997-01-01

    In a small number of cases the co-existence of primary biliary cirrhosis and sarcoidosis is assumed from clinical serological and histological findings. A case of sarcoidosis is reported in which the M2 antibody, a highly specific marker for primary biliary cirrhosis, was detected. The patient also developed a severe myositis and a possible overlap syndrome is discussed. 




 PMID:9059489

  7. The association between osteopontin gene polymorphisms, osteopontin expression and sarcoidosis

    PubMed Central

    Lavi, Hadas; Assayag, Miri; Schwartz, Assaf; Arish, Nissim; Fridlender, Zvi G.; Berkman, Neville

    2017-01-01

    Background Sarcoidosis is a systemic inflammatory disease of unknown etiology. Osteopontin (SPP1, OPN) is an extra cellular matrix glycoprotein and cytokine with a known role in granuloma formation and in autoimmune and inflammatory diseases. Objective To determine whether plasma OPN levels are elevated in patients with sarcoidosis and compare the frequency of four single nucleotide polymorphism (SNPs) variants in the OPN gene in sarcoidosis patients compared to healthy controls. Methods Demographic and clinical information, radiological studies and pulmonary function tests were evaluated in 113 patients with sarcoidosis and in 79 healthy controls. Blood samples were analyzed for SNPs of the OPN gene and for plasma OPN and CRP levels. Association between clinical features of disease and OPN levels as well as SNP frequencies was determined. Results Plasma OPN levels were higher in sarcoidosis patients than in healthy subjects, (median: 217 vs 122ng/ml, p<0.001). Area under the curve for receiver operator curves (ROC) was 0.798 (0.686–0.909 95% CI.) No differences were observed between sarcoidosis patients and controls in the frequency of any of the SNPs evaluated. Presence of lung parenchymal involvement was associated with SNP distribution at rs1126772 (p = 0.02). We found no correlation between SNPs distribution and plasma OPN levels. Conclusions Osteopontin protein levels are elevated in sarcoidosis. We found no evidence for an association between SNPs on the osteopontin gene and plasma OPN levels or the presence of sarcoidosis, however, an association between genotype and several phenotypic clinical parameters of disease was observed. PMID:28253271

  8. Ocular Sarcoidosis Limited to Retinal Vascular Ischemia and Neovascularization

    PubMed Central

    Dyer, Gawain; Shaikh, Saad

    2016-01-01

    A 59-year-old Caucasian male experienced progressive vision loss secondary to retinal vascular ischemia and neovascularization. At no time did he present with uveitis or vasculitis, and his serology tests were all negative. He was soon after diagnosed with sarcoidosis by hilar lymph node lung biopsy. Our patient demonstrates an atypical presentation of ocular sarcoidosis, manifesting solely as neovascularization and retinal vascular ischemia. Ophthalmologists should consider proliferative sarcoid retinopathy in patients with neovascularization. PMID:27928517

  9. Cardiac Sarcoidosis Diagnosed by Incidental Lymph Node Biopsy.

    PubMed

    Matsuda, Jun; Fujiu, Katsuhito; Roh, Solji; Tajima, Miyu; Maki, Hisataka; Kojima, Toshiya; Ushiku, Tetsuo; Nawata, Kan; Takeda, Norihiko; Watanabe, Masafumi; Akazawa, Hiroshi; Komuro, Issei

    2017-02-07

    Cardiac involvement in systemic sarcoidosis sometimes provokes life-threatening ventricular tachyarrhythmia. Steroid administration is one of the fundamental anti-arrhythmia therapies. For an indication of steroid therapy, a definitive diagnosis of sarcoidosis is required.(1)) However, cases that are clearly suspected of cardiac sarcoidosis based on their clinical courses sometimes do not meet the current diagnostic criteria and result in the loss of an appropriate opportunity to perform steroid therapy.Here we report a case that was diagnosed as sarcoidosis by incidental biopsy of an inguinal lymph node during cardiac resuscitation for cardiac tamponade.(2)) While the inguinal lymph node was not swollen on computed tomography, a specimen obtained from an incidental biopsy during the exposure of a femoral vessel for the establishment of extracorporeal cardio-pulmonary resuscitation showed a non-caseating granuloma.This findings suggest a non-swelling lymph node biopsy might be an alternative strategy for the diagnosis for sarcoidosis if other standard strategies do not result in a diagnosis of sarcoidosis.

  10. "End-stage" pulmonary fibrosis in sarcoidosis.

    PubMed

    Teirstein, Alvin T; Morgenthau, Adam S

    2009-02-01

    Pulmonary fibrosis is an unusual "end stage" in patients with sarcoidosis. Fibrosis occurs in a minority of patients, and presents with a unique physiologic combination of airways dysfunction (obstruction) superimposed on the more common restrictive dysfunction. Imagin techniques are essential to the diagnosis, assessment and treatment of pulmonary fibrosis. Standard chest radiographs and CT scans may reveal streaks, bullae, cephalad retraction of the hilar areas, deviation of the trachea and tented diaphragm. Positive gallium and PET scans indicate residual reversible granulomatous disease and are important guides to therapy decisions. Treatment, usually with corticosteroids, is effective in those patients with positive scans, but fibrosis does not improve with any treatment. With severe functional impariment and patient disability, pulmonary hypertension and right heart failure may supervene for which the patient will require treatment. Oxygen, careful diuresis, sildenafil and bosentan may be salutary. These patients are candidates for lung transplantation.

  11. Successful treatment of refractory midgut bleeding with ocreotide and corticosteroids in a dialysis patient with suspected sarcoidosis.

    PubMed

    Velasco, Nestor; Imtiaz, Toufeeq; Shah, Amir Ali; Koulaouzidis, Anastasios

    2016-07-14

    We present a case of severe and recurrent small-bowel bleeding, due to multiple intestinal angiodysplasias, in a female patient with chronic renal failure due to suspected sarcoidosis. Over the years, she required numerous admissions and >200 units of blood for symptomatic anaemia. However, following a small-bowel capsule endoscopy that revealed several small-bowel angiectasis, she was treated successfully with octreotide and corticosteroids. Her transfusion requirements and hospital admissions were reduced drastically. Moreover, hypercalcaemia and liver function tests also normalised after treatment and double-balloon enteroscopy confirmed the complete resolution of these angiodysplasias. This case presentation confirms the usefulness of octreotide in the management of small-bowel angiodysplasias in dialysis patients and highlights the additional benefit of corticosteroids in portal hypertension due to suspected sarcoidosis.

  12. Rationale and Design of the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) Study. Sarcoidosis Protocol

    PubMed Central

    Koth, Laura L.; Maier, Lisa A.; Morris, Alison; Drake, Wonder; Rossman, Milton; Leader, Joseph K.; Collman, Ronald G.; Hamzeh, Nabeel; Sweiss, Nadera J.; Zhang, Yingze; O’Neal, Scott; Senior, Robert M.; Becich, Michael; Hochheiser, Harry S.; Kaminski, Naftali; Wisniewski, Stephen R.; Gibson, Kevin F.

    2015-01-01

    Sarcoidosis is a systemic disease characterized by noncaseating granulomatous inflammation with tremendous clinical heterogeneity and uncertain pathobiology and lacking in clinically useful biomarkers. The Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) study is an observational cohort study designed to explore the role of the lung microbiome and genome in these two diseases. This article describes the design and rationale for the GRADS study sarcoidosis protocol. The study addresses the hypothesis that distinct patterns in the lung microbiome are characteristic of sarcoidosis phenotypes and are reflected in changes in systemic inflammatory responses as measured by peripheral blood changes in gene transcription. The goal is to enroll 400 participants, with a minimum of 35 in each of 9 clinical phenotype subgroups prioritized by their clinical relevance to understanding of the pathobiology and clinical heterogeneity of sarcoidosis. Participants with a confirmed diagnosis of sarcoidosis undergo a baseline visit with self-administered questionnaires, chest computed tomography, pulmonary function tests, and blood and urine testing. A research or clinical bronchoscopy with a research bronchoalveolar lavage will be performed to obtain samples for genomic and microbiome analyses. Comparisons will be made by blood genomic analysis and with clinical phenotypic variables. A 6-month follow-up visit is planned to assess each participant’s clinical course. By the use of an integrative approach to the analysis of the microbiome and genome in selected clinical phenotypes, the GRADS study is powerfully positioned to inform and direct studies on the pathobiology of sarcoidosis, identify diagnostic or prognostic biomarkers, and provide novel molecular phenotypes that could lead to improved personalized approaches to therapy for sarcoidosis. PMID:26193069

  13. Rationale and Design of the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) Study. Sarcoidosis Protocol.

    PubMed

    Moller, David R; Koth, Laura L; Maier, Lisa A; Morris, Alison; Drake, Wonder; Rossman, Milton; Leader, Joseph K; Collman, Ronald G; Hamzeh, Nabeel; Sweiss, Nadera J; Zhang, Yingze; O'Neal, Scott; Senior, Robert M; Becich, Michael; Hochheiser, Harry S; Kaminski, Naftali; Wisniewski, Stephen R; Gibson, Kevin F

    2015-10-01

    Sarcoidosis is a systemic disease characterized by noncaseating granulomatous inflammation with tremendous clinical heterogeneity and uncertain pathobiology and lacking in clinically useful biomarkers. The Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) study is an observational cohort study designed to explore the role of the lung microbiome and genome in these two diseases. This article describes the design and rationale for the GRADS study sarcoidosis protocol. The study addresses the hypothesis that distinct patterns in the lung microbiome are characteristic of sarcoidosis phenotypes and are reflected in changes in systemic inflammatory responses as measured by peripheral blood changes in gene transcription. The goal is to enroll 400 participants, with a minimum of 35 in each of 9 clinical phenotype subgroups prioritized by their clinical relevance to understanding of the pathobiology and clinical heterogeneity of sarcoidosis. Participants with a confirmed diagnosis of sarcoidosis undergo a baseline visit with self-administered questionnaires, chest computed tomography, pulmonary function tests, and blood and urine testing. A research or clinical bronchoscopy with a research bronchoalveolar lavage will be performed to obtain samples for genomic and microbiome analyses. Comparisons will be made by blood genomic analysis and with clinical phenotypic variables. A 6-month follow-up visit is planned to assess each participant's clinical course. By the use of an integrative approach to the analysis of the microbiome and genome in selected clinical phenotypes, the GRADS study is powerfully positioned to inform and direct studies on the pathobiology of sarcoidosis, identify diagnostic or prognostic biomarkers, and provide novel molecular phenotypes that could lead to improved personalized approaches to therapy for sarcoidosis.

  14. The alveolitis of pulmonary sarcoidosis. Evaluation of natural history and alveolitis-dependent changes in lung function

    SciTech Connect

    Keogh, B.A.; Hunninghake, G.W.; Line, B.R.; Crystal, R.G.

    1983-08-01

    Current concepts of the pathogenesis of pulmonary sarcoidosis suggest that a mononuclear cell alveolitis, comprised of activated T-lymphocytes and activated alveolar macrophages, precedes and modulates the formation of granuloma and fibrosis. To evaluate the natural history of this alveolitis and determine the relationship it has to subsequent changes in lung function, 19 untreated patients with pulmonary sarcoidosis without extrapulmonary manifestations were studied with bronchoalveolar lavage, /sup 67/Ga scanning, and pulmonary function tests to evaluate lung T-cells, lung alveolar macrophages, and lung function, respectively. In patients with sarcoidosis, low intensity alveolitis (lung T-cells less than or equal to 28% of all lung effector cells and/or /sup 67/Ga scan negative) was much more common (80% of all observations) than high intensity alveolitis (lung T-cells greater than 28% and /sup 67/Ga scan positive, 20% of all observations). Conventional clinical, roentgenographic, or physiologic studies could not predict the alveolitis status. Interestingly, of the 51 alveolitis evaluations in the 19 patients, there were 24 occurrences (47%) where the alveolitis was ''split,'' i.e., /sup 67/Ga scans positive and T-cells low (39%) or /sup 67/Ga negative and T-cells high (8%). Most untreated patients with sarcoidosis without extrapulmonary symptoms may have some inflammatory processes ongoing in their alveolar structures. Overall, whenever a high intensity alveolitis episode occurred, it was followed by deterioration over the next 6 months in at least one lung function parameter. A low intensity alveolitis episode was followed by functional deterioration only 8% of the time. The alveolitis parameters (lavage and /sup 67/Ga scanning) clearly predicted prognosis. These observations should prove useful in understanding the natural history of pulmonary sarcoidosis, in staging patients with this disease, and in making rational therapy decisions.

  15. Delayed diagnosis of sarcoidosis is common in Brazil*

    PubMed Central

    Rodrigues, Mauri Monteiro; Coletta, Ester Nei Aparecida Martins; Ferreira, Rimarcs Gomes; Pereira, Carlos Alberto de Castro

    2013-01-01

    OBJECTIVE: To determine the frequency of and the factors related to delayed diagnosis of sarcoidosis in Brazil. METHODS: We evaluated patients with a biopsy-proven diagnosis of sarcoidosis, using a questionnaire that addressed the following: time since symptom onset and since the first medical visit; and the number and specialty of the physicians visited. We divided the patients by the timeliness of the diagnosis-timely (< 6 months) and delayed (≥ 6 months)-comparing the two groups in terms of systemic and pulmonary symptoms; extrathoracic involvement; spirometric data; radiological staging; level of education; income; and tuberculosis (diagnosis and treatment). RESULTS: We evaluated 100 patients. The median number of physicians consulted was 3 (range, 1-14). In 11 cases, sarcoidosis was diagnosed at the first visit. In 54, the first physician seen was a general practitioner. The diagnosis of sarcoidosis was timely in 41 patients and delayed in 59. The groups did not differ in terms of gender; race; type of health insurance; level of education; income; respiratory/systemic symptoms; extrathoracic involvement; and radiological staging. In the delayed diagnosis group, FVC was lower (80.3 ± 20.4% vs. 90.5 ± 17.1%; p = 0.010), as was FEV1 (77.3 ± 19.9% vs. 86.4 ± 19.5%; p = 0.024), misdiagnosis with and treatment for tuberculosis (≥ 3 months) also being more common (24% vs. 7%, p = 0.032, and 20% vs. 0%; p = 0.002, respectively). CONCLUSIONS: The diagnosis of sarcoidosis is often delayed, even when the imaging is suggestive of sarcoidosis. Delayed diagnosis is associated with impaired lung function at the time of diagnosis. Many sarcoidosis patients are misdiagnosed with and treated for tuberculosis. PMID:24310626

  16. Older Adults, Chronic Disease and Leisure-time Physical Activity

    PubMed Central

    Ashe, Maureen C.; Miller, William C.; Eng, Janice J.; Noreau, Luc

    2011-01-01

    Background Participating in regular physical activity is an important part of healthy aging. There is an increased risk for inactivity associated with aging and the risk becomes greater for adults who have a chronic disease. However, there is limited information on current physical activity levels for older adults and even less for those with chronic diseases. Objective Our primary objective was to determine the proportion of older adults who achieved a recommended amount of weekly physical activity (≥1000 kcal/week). The secondary objectives were to identify variables associated with meeting guideline leisure-time physical activity (LTPA), and to describe the type of physical activities that respondents reported across different chronic diseases. Methods In this study we used the Canadian Community Health Survey Cycle 1.1 (2000/2001) to report LTPA for adults aged 65 years and older. This was a population-based self-report telephone survey. We used univariate logistic regression to provide odds ratios to determine differences in activity and the likelihood of meeting guideline recommendations. Results For adults over 65 years of age with no chronic diseases, 30% reported meeting guideline LTPA, while only 23% met the recommendations if they had one or more chronic diseases. Factors associated with achieving the guideline amount of physical activity included a higher level of education, higher income and moderate alcohol consumption. Likelihood for not achieving the recommended level of LTPA included low BMI, pain and the presence of mobility and dexterity problems. Walking, gardening and home exercises were the three most frequent types of reported physical activities. Conclusion This study provides the most recent evidence to suggest that older Canadians are not active enough and this is accentuated if a chronic disease is present. It is important to develop community-based programs to facilitate LTPA, in particular for older people with a chronic disease. PMID

  17. Carpal Tunnel Syndrome in Sarcoidosis: A Case Report of a Rare Neurologic Manifestation

    PubMed Central

    Sonambekar, Ajinkya; Gupta, Nikhil; Swadi, Akanksha; Tomar, Laxmikant Ramkumarsingh

    2016-01-01

    Introduction Sarcoidosis is a multisystemic inflammatory disease with myriad clinical manifestations. Neurologic involvement in sarcoidosis is uncommon. Peripheral neuropathic presentations include mononeuropathy, mononeuritis multiplex, and generalized sensory, motor, autonomic, and sensorimotor polyneuropathies. Case Presentation We report a case of carpal tunnel syndrome caused by sarcoidosis in a 30-year-old woman. Other causes of carpal tunnel syndrome were ruled out. The patient responded well to the standard line of corticosteroid treatment and wrist splinting. Discussion Carpal tunnel syndrome caused by sarcoidosis is a rare presentation. The mechanism of neurologic involvement in sarcoidosis is not clear. PMID:27643973

  18. Angiotensin II, sympathetic nerve activity and chronic heart failure.

    PubMed

    Wang, Yutang; Seto, Sai-Wang; Golledge, Jonathan

    2014-03-01

    Sympathetic nerve activity has been reported to be increased in both humans and animals with chronic heart failure. One of the mechanisms believed to be responsible for this phenomenon is increased systemic and cerebral angiotensin II signaling. Plasma angiotensin II is increased in humans and animals with chronic heart failure. The increase in angiotensin II signaling enhances sympathetic nerve activity through actions on both central and peripheral sites during chronic heart failure. Angiotensin II signaling is enhanced in different brain sites such as the paraventricular nucleus, the rostral ventrolateral medulla and the area postrema. Blocking angiotensin II type 1 receptors decreases sympathetic nerve activity and cardiac sympathetic afferent reflex when therapy is administered to the paraventricular nucleus. Injection of an angiotensin receptor blocker into the area postrema activates the sympathoinhibitory baroreflex. In peripheral regions, angiotensin II elevates both norepinephrine release and synthesis and inhibits norepinephrine uptake at nerve endings, which may contribute to the increase in sympathetic nerve activity seen in chronic heart failure. Increased circulating angiotensin II during chronic heart failure may enhance the sympathoexcitatory chemoreflex and inhibit the sympathoinhibitory baroreflex. In addition, increased circulating angiotensin II can directly act on the central nervous system via the subfornical organ and the area postrema to increase sympathetic outflow. Inhibition of angiotensin II formation and its type 1 receptor has been shown to have beneficial effects in chronic heart failure patients.

  19. Bone cysts in sarcoidosis: what is their clinical significance?

    PubMed

    Yanardağ, Halil; Pamuk, Omer Nuri

    2004-09-01

    The incidence of bone cysts in sarcoidosis, a multisystemic disease, varies in different series, and these cysts are generally asymptomatic. We evaluated bone cysts in 516 sarcoidosis patients with available hand X-rays and in 200 patients with foot X-rays. Bone cysts were present in 21 cases (19 females, two males). The cysts were localized in phalanges of the hand in all cases, in feet in five cases, and in nasal bone in one. Six patients with bone cysts also had lupus pernio. Among those with cystic bone lesions, females were more frequent; extrapulmonary and skin involvement and lupus pernio were significantly more common. We diagnosed cystic bone lesions in 3.6% of our sarcoidosis patients and conclude that cysts were more frequent in females and in patients with lupus pernio.

  20. Anomalies in the dominant sarcoidosis paradigm justify its displacement.

    PubMed

    Reich, Jerome M

    2017-04-01

    The prevailing paradigm defines sarcoidosis as a disease of unknown etiology characterized by a systemic noncaseating epithelioid granulomatous response (SGR). This formulation fails to account for the elusiveness of the etiological agent, the nature of the Kveim response, the paradox of cutaneous delayed type hypersensitivity anergy in a setting of intense immune response and the appearance of SGR, indistinguishable from sarcoidosis, in persons with lymphohematogenous and solid neoplasms and a variety of cellular immune deficiencies. Displacing this formulation with an evidence-based alternative in which the SGR is viewed as an etiologically diverse, primitive immunological fallback due to inefficient cellular immune processing eliminates these shortcomings, providing a unifying accounting for the puzzles and violations of expectations associated with the prevailing paradigm. Its clinical import resides in the reported annual three-percent increase in sarcoidosis mortality in the past two decades (Swigris et al., 2011), which may be attributable, in part, to unneeded suppressive treatment.

  1. Sarcoidosis detected due to tattoo swellings in an Indian female.

    PubMed

    Ghorpade, Ashok

    2015-01-01

    A female patient presented with asymptomatic swellings in old blue-black tattoo marks of her forearms. On careful skin examination, few raised erythematous, circular plaques were also found on the non-tattooed skin on her back, about which she was unaware. The diagnosis of cutaneous and systemic sarcoidosis was confirmed after classical histopathological findings from skin lesions from her non tattooed back and from papulonodular tattooed lesions, ruling out other causes of granulomas and supported by a negative Mantoux test, raised serum angiotensin converting enzyme level, high resolution computed tomography thorax, etc. She responded well to oral steroid therapy. The importance of a careful skin examination, easy access provided by skin lesions in suspected cases of cutaneous/systemic sarcoidosis, the value of sudden tattoo changes in the diagnosis here and the possible contribution of tattoos toward the causation of cutaneous and/or systemic sarcoidosis are highlighted.

  2. A case of acute kidney injury caused by granulomatous tubulointerstitial nephritis associated with sarcoidosis and concomitant presence of anti-glomerular basement membrane antibody.

    PubMed

    Yoshinori, Kamata; Arata, Azuma; Osamu, Hotta; Kensuke, Joh

    2016-01-18

    We encountered a case of granulomatous tubulointerstitial nephritis in a patient with sarcoidosis, who was also found to show an elevated serum titer of anti-glomerular basement membrane (GBM) antibody. The serum creatinine level had been documented to be within normal range 8 months before the first visit. Gallium scintigraphy revealed bilateral kidney uptake, but no uptake in the pulmonary hilum. No typical findings of sarcoidosis, e.g., bilateral hilar adenopathy, uveitis or elevated serum ACE level were recognized in the early stage. Echocardiography showed basal thinning of the interventricular septum, a specific feature of cardiac sarcoidosis, and hilar lymph node uptake on gallium scintigraphy and anterior uveitis appeared during the disease course. Active tuberculosis, fungal infection, vasculitis and malignancy were clinically excluded. We performed a renal biopsy. Light microscopy revealed non-caseating granulomatous tubulointerstitial nephritis with multinucleated giant cells and normal glomeruli. Inflammatory reaction was seen only within the interstitial tubules. The serum creatinine level had increased to 4.52 mg/dl. The patient was administered methylprednisolone pulse therapy, followed by administration of oral prednisolone. The renal function improved immediately in response to this therapy. Based on the above, we made the final diagnosis of granulomatous tubulointerstitial nephritis associated with sarcoidosis. While the serum titer of anti- GBM antibody was elevated, to our surprise, renal biopsy did not reveal linear anti-GBM antibody staining in this case. Furthermore, interestingly, the serum anti-GBM antibody titer in our patient decreased in parallel with the clinical improvement of sarcoidosis. Severe and progressive renal dysfunction was the most prominent clinical feature without other organ manifestations in our patient, which is a rare occurrence in sarcoidosis.

  3. Adipophilin expression in necrobiosis lipoidica, granuloma annulare, and sarcoidosis.

    PubMed

    Schulman, Joshua M; LeBoit, Philip E

    2015-03-01

    Necrobiosis lipoidica (NL), granuloma annulare (GA), and sarcoidosis usually are distinguished by clinical presentation and routine microscopy, but their distinction can sometimes be challenging. Historically, a clue to diagnosing NL or GA has been the identification of lipid droplets in the areas of altered collagen, but such studies have required fresh frozen tissue, making them impractical. Here, we present the first report of immunohistochemical staining to detect adipophilin, a membrane protein in lipid droplets, in NL (n = 12), GA (n = 19), sarcoidosis (n = 12), and, as a control for nonspecific tissue damage, nongranulomatous cutaneous necrosis (n = 13). Four patterns of labeling were identified: (1) extracellular, within zones of altered collagen; (2) both intracellular and extracellular, after the distribution of palisaded or scattered histiocytes; (3) intracellular, within clustered histiocytes; and (4) periadnexal. All cases of NL demonstrated pattern 1; nearly all cases of GA (18/19) demonstrated pattern 2; most sarcoidosis (10/12) demonstrated pattern 3; and nongranulomatous necrosis demonstrated either pattern 4 (6/13) or did not stain (6/13), confirming that the antibody to adipophilin did not adhere nonspecifically to the damaged tissue. An additional set of 3 biopsies with overlapping or partially sampled features of NL, GA, and/or sarcoidosis subsequently confirmed the potential utility of adipophilin staining in diagnostically challenging cases. We conclude that the pattern of adipophilin expression is a useful adjunct in the evaluation of granulomatous dermatitis.

  4. Renal failure due to granulomatous interstitial nephritis after pulmonary sarcoidosis.

    PubMed

    van Dorp, W T; Jie, K; Lobatto, S; Weening, J J; Valentijn, R M

    1987-01-01

    Two patients, who had had pulmonary sarcoidosis, developed renal failure due to sarcoid granulomatous interstitial nephritis after their original pulmonary symptoms had subsided. Treatment with prednisone resulted in almost complete recovery of renal function. Lysozyme and angiotensin-converting enzyme levels and gallium scintigraphy can be of diagnostic value.

  5. Unilateral apical infiltrate as an initial presentation of pulmonary sarcoidosis.

    PubMed

    Tice, A W

    1981-11-01

    A unilateral, apical, pulmonary infiltrate was seen in an Air Force weapon systems officer stationed in the Philippines as an initial presentation of pulmonary sarcoidosis. The most obvious diagnosis for that geographic area is tuberculosis. Diagnosis must be pursued to evaluate all differential possibilities, with resort to open-lung or bronchoscopic biopsy, if necessary.

  6. Multifactorial Etiology Pulmonary Hypertension in a Patient with Sarcoidosis

    PubMed Central

    Lucas Vinícius da Fonseca, Barreto; Felipe Naze Rodrigues, Cavalcante; Joselina Luzia Menezes, Oliveira; Marcos Antônio, Almeida-Santos; José Augusto Soares, Barreto-Filho; Antônio Carlos Sobral, Sousa

    2016-01-01

    Differential diagnosis between pre- and postcapillary pulmonary hypertension (PH) in patients with diastolic heart failure (DHF) is a challenge in clinical practice. The presence of PH is implicated in worse prognosis in patients with this disease. This case report approaches the process of investigation of pulmonary hypertension in adult patient with DHF, double mitral lesion, and sarcoidosis with poor clinical outcome. PMID:27800190

  7. Systemic sarcoidosis complicated of acute renal failure: about 12 cases.

    PubMed

    Mahfoudhi, Madiha; Mamlouk, Habiba; Turki, Sami; Kheder, Adel

    2015-01-01

    The sarcoidosis is a systemic granulomatosis affecting most frequently the lungs and the mediastinum. An acute renal failure reveals exceptionally this disease. It's a retrospective study implicating 12 cases of sarcoidosis complicated of acute renal failure. The aim of this study is to determine epidemiological, clinical, biological and histological profile in these cases and then to indicate the interest to consider the diagnosis of sarcoidosis in cases of unexplained renal failure. Extra-renal complications, therapeutic modalities and the outcome were determined in all patients. Our series involved 12 women with an average age of 40 years. Biological investigations showed an abnormal normocalcemia in 7 cases, a hypercalcemia in 5 cases, a hypercalciuria in 10 cases and polyclonal hypergammaglobulinemia in 7 cases. An acute renal failure was found in all patients with a median creatinin of 520 umol/L. For all patients, the renal echography was normal however, the kidney biopsy showed tubulo-interstitial nephritis. The extra-renal signs highlighting pulmonary interstitial syndrome in 5 cases, a sicca syndrome in 4 cases, mediastinal lymph nodes in 2 cases, a lymphocytic alveolitis in 3 cases, an anterior granulomatous uveitis in 2 cases and a polyarthritis in 5 cases. Five patients benefited of hemodialysis. The treatment consisted of corticosteroid in all cases. The follow up was marked by complete resolution of clinical and biological signs. The diagnosis of renal sarcoidosis must be done quickly to prevent renal failure.

  8. Physical activity buffers fatigue only under low chronic stress.

    PubMed

    Strahler, Jana; Doerr, Johanna M; Ditzen, Beate; Linnemann, Alexandra; Skoluda, Nadine; Nater, Urs M

    2016-09-01

    Fatigue is one of the most commonly reported complaints in the general population. As physical activity (PA) has been shown to have beneficial effects, we hypothesized that everyday life PA improves fatigue. Thirty-three healthy students (21 women, 22.8 ± 3.3 years, 21.7 ± 2.3 kg/m(2)) completed two ambulatory assessment periods. During five days at the beginning of the semester (control condition) and five days during final examination preparation (examination condition), participants repeatedly reported on general fatigue (awakening, 10 am, 2 pm, 6 pm and 9 pm) by means of an electronic diary, collected saliva samples for the assessment of cortisol and α-amylase immediately after providing information on fatigue and wore a triaxial accelerometer to continuously record PA. Self-perceived chronic stress was assessed as a moderator. Using hierarchical linear modeling, including PA, condition (control vs. examination), sex and chronic stress as predictors, PA level during the 15 min prior to data entry did not predict momentary fatigue level. Furthermore, there was no effect of condition. However, a significant cross-level interaction of perceived chronic stress with PA was observed. In fact, the (negative) relationship between PA and fatigue was stronger in those participants with less chronic stress. Neither cortisol nor α-amylase was significantly related to physical activity or fatigue. Our study showed an immediate short-term buffering effect of everyday life PA on general fatigue, but only when experiencing lower chronic stress. There seems to be no short-term benefit of PA in the face of higher chronic stress. These findings highlight the importance of considering chronic stress when evaluating the effectiveness of PA interventions in different target populations, in particular among chronically stressed and fatigued subjects.

  9. Pulmonary sarcoidosis is associated with high-level inducible co-stimulator (ICOS) expression on lung regulatory T cells--possible implications for the ICOS/ICOS-ligand axis in disease course and resolution.

    PubMed

    Sakthivel, P; Grunewald, J; Eklund, A; Bruder, D; Wahlström, J

    2016-02-01

    Sarcoidosis is a granulomatous inflammatory disorder of unknown aetiology. The increased frequency of activated lung CD4(+) T cells with a T helper type 1 (Th1) cytokine profile in sarcoidosis patients is accompanied by a reduced proportion and/or impaired function of regulatory T cells (Tregs ). Here we evaluated the expression of the inducible co-stimulator (ICOS) on lung and blood CD4(+) T cell subsets in sarcoidosis patients with different prognosis, by flow cytometry. Samples from the deep airways were obtained by bronchoalveolar lavage (BAL). We show that Tregs from the inflamed lung of sarcoidosis patients were characterized by a unique ICOS(high) phenotype. High-level ICOS expression was restricted to Tregs from the inflamed lung and was absent in blood Tregs of sarcoidosis patients as well as in lung and blood Tregs of healthy volunteers. In addition, lung Tregs exhibited increased ICOS expression compared to sarcoid-specific lung effector T cells. Strikingly, ICOS expression on Tregs was in particularly high in the lungs of Löfgren's syndrome (LS) patients who present with acute disease which often resolves spontaneously. Moreover, blood monocytes from LS patients revealed increased ICOS-L levels compared to healthy donors. Sarcoidosis was associated with a shift towards a non-classical monocyte phenotype and the ICOS-L(high) phenotype was restricted to this particular monocyte subset. We propose a potential implication of the ICOS/ICOS-L immune-regulatory axis in disease activity and resolution and suggest to evaluate further the suitability of ICOS as biomarker for the prognosis of sarcoidosis.

  10. Clinical presentations and diagnostic work-up in sarcoidosis: a series of Turkish cases (clinics and diagnosis of sarcoidosis).

    PubMed

    Kıter, Göksel; Müsellim, Benan; Cetinkaya, Erdoğan; Türker, Hatice; Kunt Uzaslan, A Esra; Yentürk, Esin; Uzun, Oğuz; Sağlam, Leyla; Özdemir Kumbasar, Özlem; Celik, Gökhan; Okumuş, Gülfer; Arbak, Peri Meram; Altıay, Gündeniz; Tabak, Levent; Sakar Coşkun, Ayşın; Erturan, Serdar; Türktaş, Haluk; Yalnız, Enver; Akkoçlu, Atilla; Öğüş, Candan; Doğan, Ömer Tamer; Özkan, Metin; Özkan, Serir; Uzel, Fatma Işıl; Öngen, Gül

    2011-01-01

    Sarcoidosis is an idiopathic granulomatous disease. It usually affects the lung. The diagnosis may be problematic since the known causes of granulomatous inflammation must be excluded. This multicenter study aimed to evaluate the clinical presentations and diagnostic approaches of sarcoidosis. The study protocol was sent via internet, and the participants were asked to send the information (clinical, radiological and diagnostic) on newly diagnosed sarcoidosis cases. 293 patients were enrolled within two years. Pulmonary symptoms were found in 73.3% of the patients, and cough was the most common one (53.2%), followed by dyspnea (40.3%). Constitutional symptoms were occured in half of the patients. The most common one was fatigue (38.6%). The most common physical sign was eritema nodosum (17.1%). The most common chest radiograhical sign was bilateral hilar lymphadenomegaly (78.8%). Staging according to chest X-ray has revealed that most of the patients were in Stage I and Stage II (51.9% and 31.7%, respectively). Sarcoidosis was confirmed histopathologically in 265 (90.4%) patients. Although one-third of the bronchoscopy was revealed normal, mucosal hyperemi (19.8%) and external compression of the bronchial wall (16.8%) were common abnormal findings. The 100% success rate was obtained in mediastinoscopy among the frequently used sampling methods. Transbronchial biopsy was the most frequently used method with 48.8% success rate. Considering sarcoidosis with its most common and also rare findings in the differential diagnosis, organizing the related procedures according to the possibly effected areas, and the expertise of the team would favour multimodality diagnosis.

  11. Key messages from a rare case of annular sarcoidosis of scalp

    PubMed Central

    Bhushan, Premanshu; Thatte, Sarvesh S.; Singh, Avninder

    2016-01-01

    Sarcoidosis, a multisystem disease of obscure etiology, is characterized by the formation of noncaseating epithelioid cell granulomas in several organs or tissues. The diagnosis of sarcoidosis requires a compatible clinical picture, histologic demonstration of noncaseating granulomas, and exclusion of other diseases capable of producing similar histology or clinical features. The lung is the most commonly affected organ, but the skin is frequently involved. Sarcoidosis occurs worldwide and affects all ages and races with female predominance. Scalp involvement is decidedly rare among the myriad cutaneous manifestations of sarcoidosis. Alopecia is common in sarcoidosis and is generally scarring in nature. Annular sarcoidosis is a rare morphology and annular sarcoid of scalp is seldom reported. Herein we present a case of annular scalp sarcoid with systemic involvement and without alopecia. PMID:27294057

  12. [Chronic active hepatitis: clinical, biochemical, and histopathologic correlation].

    PubMed

    Subauste, M C

    1989-01-01

    A retrospective study over 26 female patients with chronic active hepatitis was made. The mean age was 39 years old, the mean length of illness of 8 months; 5 patients had positive markers for hepatitis B. Patients were selected with the grade of histological activity: 8 patients had a mild form from disease (2A) and 16 with a severe one (2B). The predominant group was 2B. Severe inflammatory infiltration was the hallmark and multiobulillar necrosis, bridging, eosinophils and hiperplasia of kuppfer cells were found only in this group. Clinical features range from hepatic manifestations to systemic ones. Chronic active hepatitis may present with cholestasis, but the latter is not always related with the grade of activity. Group 2B had elevated aminotransferases and a low concentration for protrobine.

  13. Comorbid autoimmune diseases in patients with sarcoidosis: A nationwide case-control study in Taiwan.

    PubMed

    Wu, Chi-Hung; Chung, Pei-I; Wu, Chen-Yi; Chen, Yen-Ta; Chiu, Yun-Wen; Chang, Yun-Ting; Liu, Han-Nan

    2017-04-01

    The association between sarcoidosis and autoimmune comorbidities has been reported, however, it has seldom been confirmed by a large nationwide study. Our study aimed to clarify the association between sarcoidosis and autoimmune comorbidities in the Taiwanese. A total of 1237 patients with sarcoidosis and 4948 age- and sex-matched control subjects were selected from the National Health Insurance Research Database of Taiwan from 1997 to 2010. Multiple logistic regressions were performed to calculate the odds of comorbidities between the two groups. The prevalence of sarcoidosis was 2.17/100 000 individuals in Taiwan. Sarcoidosis patients tended to run a higher risk of autoimmune comorbidities than the control group (17.6% vs 9.4%, P < 0.05). Autoimmune thyroid disease (adjusted odd ratio [aOR], 1.32; 95% confidence interval [CI], 1.05-1.64), Sjögren's syndrome (aOR, 11.6; 95% CI, 4.36-31.0) and ankylosing spondylitis (aOR, 3.80; 95% CI, 2.42-5.97) were significantly associated with sarcoidosis. The sex-stratified analyses were carried out to demonstrate a significant association of sarcoidosis with ankylosing spondylitis in both sexes, but with autoimmune thyroid disease in male patients and with Sjögren's syndrome female patients, respectively. Besides, the diagnosis of the autoimmune comorbidities strongly associated with sarcoidosis tended to be established after that of sarcoidosis. This study demonstrated that patients with sarcoidosis tended to have autoimmune thyroid disease, Sjögren's syndrome and ankylosing spondylitis, and the diagnosis of sarcoidosis usually preceded that of associated comorbidities. Clinicians should be alert to autoimmune comorbidities in patients with sarcoidosis.

  14. Refractory pulmonary sarcoidosis – proposal of a definition and recommendations for the diagnostic and therapeutic approach

    PubMed Central

    Korsten, Peter; Strohmayer, Katharina; Baughman, Robert P.; Sweiss, Nadera J.

    2015-01-01

    Patients with sarcoidosis undergo spontaneous remission or may be effectively controlled with glucocorticoids alone in many cases. Progressive and refractory pulmonary sarcoidoisis constitute more than 10% of patients seen at specialized centers. Pulmonary fibrosis and associated complications, such as infections and pulmonary hypertension are leading causes of mortality. No universal definition of refractoriness exists, we therefore propose classifying patients as having refractory disease when the following criteria are fulfilled: (1) progressive disease despite at least 10 mg of prednisolone or equivalent for at least three months and need for additional disease-modifying anti-sarcoid drugs due to lack of efficacy, drug toxicity or intolerability and (2) treatment started for significant impairment of life due to progressive pulmonary symptoms. Both criteria should be fulfilled. Treatment options in addition to or instead of glucocorticoids for these patients include second- (methotrexate, azathioprine, leflunomide) and third-line agents (infliximab, adalimumab). Other immunmodulating agents can be used, but the evidence is very limited. Newer agents with anti-fibrotic properties, such as pirfenidone or nintedanib, might hold promise also for the pulmonary fibrosis seen in sarcoidosis. Treating physicians have to actively look for potentially treatable complications, such as pulmonary hypertension, cardiac disease or infections before patients should be classified as treatment-refractory. Ultimately, lung transplantation has to be considered as treatment option for patients not responding to medical therapy. In this review, we aim to propose a new definition of refractoriness, describe the associated clinical features and suggest the therapeutic approach. PMID:26973429

  15. Etiologic aspect of sarcoidosis as an allergic endogenous infection caused by Propionibacterium acnes.

    PubMed

    Eishi, Yoshinobu

    2013-01-01

    Sarcoidosis is a systemic granulomatous disease of unknown etiology. Propionibacterium acnes is the only microorganism that has been isolated from sarcoid lesions. Many P. acnes have been detected in sarcoid lymph nodes using quantitative PCR and in sarcoid granulomas by in situ hybridization. P. acnes trigger factor protein causes a cellular immune response only in sarcoid patients and induces pulmonary granulomas in mice sensitized with the protein and adjuvant, but only those with latent P. acnes infection in their lungs. Eradication of P. acnes by antibiotics prevents the development of granulomas in this experimental model. Although P. acnes is the most common commensal bacterium in the lungs and lymph nodes, P. acnes-specific antibody detected the bacterium within sarcoid granulomas of these organs. P. acnes can cause latent infection in the lung and lymph node and persist in a cell-wall-deficient form. The dormant form is activated endogenously under certain conditions and proliferates at the site of latent infection. In patients with P. acnes hypersensitivity, granulomatous inflammation is triggered by intracellular proliferation of the bacterium. Proliferating bacteria may escape granulomatous isolation, spreading to other organs. Latent P. acnes infection in systemic organs can be reactivated by another triggering event, leading to systemic sarcoidosis.

  16. Sarcoidosis with involvement of the paranasal sinuses - a retrospective analysis of 12 biopsy-proven cases

    PubMed Central

    2013-01-01

    Background Extrapulmonary involvement by sarcoidosis is observed in about 30–40% of patients with sarcoidosis. Little is known about the frequency and clinical characteristics of sinonasal sarcoidosis. Methods We retrospectively analyzed 12 cases of biopsy-proven sinonasal sarcoidosis. Patients were identified from a patient population of 1360 patients with sarcoidosis at the Outpatient Clinic for Sarcoidosis and Rare Lung Diseases at LungClinic Grosshansdorf, a tertiary care hospital for respiratory medicine. Results The most frequent signs and symptoms were nasal polyps (4 cases), epistaxis (3 cases), nasal crusts (8 cases) and anosmia (5 cases). Pulmonary sarcoidosis of the patients was staged as stage I (n = 1) and stage II (n = 11) on chest radiographs. Spirometry was normal in 11 patients. 7 patients had a diffusion capacity of the lung for carbon monoxide of less than 90% of predicted. Other organs were affected in 8 patients. All patients received systemic corticosteroid treatment and most patients received topical steroids. 5 patients received steroid sparing agents. Repeated sinus surgery had to be performed in 4 patients. Conclusions Sinonasal involvement is a rare disease manifestation of sarcoidosis with a frequency slightly lower than 1% in our patient population. The clinical course of sinonasal sarcoidosis can be complicated by relapse despite systemic immunosuppressive treatment and repeated sinus surgery. PMID:24070015

  17. [The morphological examination in the differential diagnosis of tuberculosis and sarcoidosis].

    PubMed

    Dvorkovskaia, I V; Maĭskaia, M Iu; Nasyrov, R A; Baranova, O P; Ariel', B M

    2014-01-01

    The paper considers the results of histological and bacterioscopic examinations of biopsy specimens from the lung and mediastinal lymph nodes of 120 patients with an unclear diagnosis of tuberculosis and sarcoidosis and with problem of their differential diagnosis. One hundred and five of these patients were microscopically diagnosed as having either tuberculosis or sarcoidosis. Additional examination of differently stained sections and that using immunohistochemical M. tuberculosis detection were conducted in 15 cases, which could diagnose tuberculosis and sarcoidosis in 7 and 8 patients, respectively. Bacterioscopic examination, in terms of extreme variability the phenotypic properties of mycobacteria, is of decisive importance in the differential diagnosis of tuberculosis and sarcoidosis.

  18. Bilateral parotitis as the initial presentation of childhood sarcoidosis.

    PubMed

    Banks, Gretchen C; Kirse, Daniel J; Anthony, Evelyn; Bergman, Simon; Shetty, Avinash K

    2013-01-01

    The differential diagnosis of bilateral parotid gland enlargement in children includes infectious, inflammatory, and neoplastic disorders. We present the case of a 13-year-old male who presented with a 5-week history of bilateral parotid swelling. On exam, both parotid glands were nontender, smooth, and diffusely enlarged. He had slightly elevated inflammatory markers, but other lab results were normal. A neck CT revealed symmetric enlargement of the parotid, submandibular, and sublingual glands. A chest CT revealed scattered peripheral pulmonary nodules and bilateral hilar adenopathy. A parotid gland biopsy showed multiple noncaseating granulomas with multinucleated giant cells surrounded by lymphocytes, consistent with the diagnosis of sarcoidosis. Special stains for acid-fast and fungal organisms were negative. Using this illustrative case, we discuss the differential diagnosis of bilateral salivary gland enlargement in children and review the etiology, diagnosis, clinical manifestations, and treatment of pediatric sarcoidosis.

  19. Diabetes insipidus secondary to sarcoidosis presenting with caseating granuloma.

    PubMed

    Alam, Taimour; Thomas, Steven

    2011-03-03

    Diabetes insipidus is a rare complication of sarcoid infiltration of the hypothalamic-pituitary region. Non-caseating granuloma formation is typical of sarcoidosis. Anterior and posterior pituitary function may be affected. MRI coupled with endocrinology assessment is the usual method of investigation. A 25-year-old Caucasian male with no significant medical history presented with polyuria and polydipsia. Water deprivation test confirmed diabetes insipidus. CT scanning of the chest confirmed lymphadenopathy. Lymph node biopsy revealed caseating granuloma. Extensive investigation for tuberculosis was negative. The patient was started on intranasal desmopressin and steroids with marked improvement in symptoms. This is the first reported case of neurosarcoidosis with diabetes insipidus and caseation on histology that we are aware of. Differentiating between caseation due to sarcoidosis and tuberculosis on histology is possible by the use of special stains. Return of normal endocrine function is unusual and the patient is likely to require desmopressin therapy for life.

  20. Hypocholesterolemia in chronic anemias with increased erythropoietic activity.

    PubMed

    Shalev, Hanna; Kapelushnik, Joseph; Moser, Asher; Knobler, Hilla; Tamary, Hannah

    2007-03-01

    Hypocholesterolemia of unknown etiology has been previously described in various chronic anemias. Few small studies also suggested that those patients have a lower incidence of atherosclerotic events. The aim of our study was to determine the extent of hypocholesterolemia in various types of anemias. We studied 59 patients with chronic anemias associated with high-erythropoietic activity (thalassemia intermedia, congenital dyserythropoietic anemia type I, congenital spherocytosis), 8 patients with low-erythropoietic activity anemias (acquired aplastic anemia, Fanconi anemia, and Diamond Blackfan anemia), and 20 healthy controls. Mean serum cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, hemoglobin, serum ferritin, soluble transferrin receptor (STR), and serum erythropoietin levels were determined in each patient. All patients with chronic anemia and increased erythropoietic activity had hypocholesterolemia, whereas none of those with low erythropoietic activity was hypocholesterolemic. Mean serum cholesterol, HDL cholesterol, and LDL cholesterol levels were found to be significantly lower in the high-erythropoietic activity group (80+/-19 mg/dl; 31+/-10 mg/dl; 35+/-14 mg/dl, respectively) compared with the control group (P<0.001; 0.001; 0.001, respectively) and the low-erythropoietic activity group (P<0.001; 0.001; 0.01, respectively). Significant inverse correlation (R2=0.507) was observed between serum cholesterol and STR levels, which in the absence of iron deficiency reflect bone marrow activity. Taken together, our results imply that hypocholesterolemia accompanies anemias with high-erythropoietic activity. We suggest that the high-erythropoitic activity-associated hypocholesterolemia is due to increased cholesterol requirements by the proliferating erythoid cells. Further studies are needed to elucidate the exact mechanism and the possible clinical consequences of this phenomenon.

  1. Sarcoidosis associated with infliximab therapy in ulcerative colitis

    PubMed Central

    Gîlcă, Georgiana-Emmanuela; Diaconescu, Smaranda; Bălan, Gheorghe Gh.; Timofte, Oana; Ştefănescu, Gabriela

    2017-01-01

    Abstract Rationale: Although immunomodulatory therapy has been clearly stated as an important landmark in treatment of ulcerative colitis, significantly improving the quality of life for patients with inflammatory bowel disease, there are several aspects to be considered regarding the possible side-effects of anti-TNF alpha agents. In spite of a good safety profile, biologic TNF antagonists may induce paradoxical inflammation, which can manifest as sarcoid-like granulomatosis, consisting of noncaseating granulomas in the affected organs. Patient concerns: We report the case of a 30-year-old male patient, with no personal or familial history of lung disease, with a personal history of ulcerative colitis (UC), under clinical remission following infliximab therapy in maintenance dose, who was admitted for treatment administration, but also for dyspnea, nocturnal sweating, and nonproductive cough. Diagnoses: Based on clinical manifestations, biological landmarks excluding various infections, CT scan, fibrobronchoscopy with bronchoalveolar lavage for culture and immunohistochemical examination, followed by mediastinoscopy with sampling of paratracheal lymph node, which underwent histopathological examination, the patient was diagnosed with drug- induced stage II pulmonary sarcoidosis. Interventions: Since the patient had developed severe allergic reaction after being administered Infliximab at admission, the biological treatment was immediately discontinued. Following the diagnosis of pulmonary sarcoidosis, corticotherapy was initiated. Patient outcomes: After corticotherapy was initiated, the patient had a favorable outcome at 3 months reevaluation, both regarding the course of ulcerative colitis and sarcoidosis. Lessons: Patients under biological therapy using anti-TNF alpha agents must be carefully monitored, in order to early identify potential paradoxical inflammation (such as sarcoidosis) as a side-effect. The drug-related pulmonary disease tends to improve upon

  2. The "mystery" of cutaneous sarcoidosis: facts and controversies.

    PubMed

    Tchernev, G; Cardoso, J C; Chokoeva, A A; Verma, S B; Tana, C; Ananiev, J; Gulubova, M; Philipov, S; Kanazawa, N; Nenoff, P; Lotti, T; Wollina, U

    2014-01-01

    The reason why the cutaneous form of sarcoidosis is well known in the literature is because of its spectrum of manifestations granting it the fame of a Great Imitator. The mystery shrouding the pathogenesis of this rare cutaneous disease is still there (in spite of the fundamental progress of the various diagnostic methods in current day medicine). The production of the morphological substrate - the epithelioid cell granuloma - which is considered to be characteristic of skin sarcoidosis, could, however, also be the end result of a reaction to i) various specific infectious agents such as Leishmaniasis cutis, coccidioidomycosis, etc., ii) certain residual bacterial or other mycobacterial antigens which, at the moment of setting the diagnosis are - by definition - non-infectious but still immunogenic, as well as iii) different tumor antigens in lesional tissue or other location. Often, differentiating between sarcodiosis and a sarcoid-like reaction, based on the updated criteria for cutaneous sarcoidosis, is problematic to downright impossible. A future characterization of the genetic signature of the two conditions, as well as the implementation of additional mandatory panels for i) the identification of certain infectious or ii) non-infectious but immunogenic and iii) tumor antigens in the epithelioid cell granuloma (or in another location in the organism), could be a considerable contribution to the process of differentiating between the two above-mentioned conditions. This will create conditions for greater accuracy when setting the subsequent therapeutic approaches.

  3. Genitourinary sarcoidosis: An essential review for the practicing clinician

    PubMed Central

    Block, Norman L.; Kava, Bruce R.

    2017-01-01

    Introduction: Sarcoidosis is a multisystem disease that commonly involves the lungs, but may also present with extrapulmonary manifestations. Genitourinary (GU) tract involvement has been traditionally thought to be rare, but that view may underestimate the true prevalence of the disease due to the often, silent presentation thereof. Methods: The literature pertaining to sarcoidosis from the general systemic point of view, etiology and therapy and with regard to specific organs was reviewed by identifying key words in a PubMed search. That material with special relevance to the Indian experience was emphasized. Results: There are a number of isolated case reports in the literature describing symptomatic and asymptomatic GU tract sarcoidosis. The world literature associated with the generalized syndrome was reviewed and summarized. Specific aspects of GU involvement are presented for each organ of the GU tract. Conclusions: It is critical for the practicing clinician to have a working knowledge of the clinical manifestations of this disease as it involves the GU tract, as well as to be able to distinguish it from tuberculosis and the various malignancies that affect this organ system. PMID:28197023

  4. Right ventricular sarcoidosis: is it time for updated diagnostic criteria?

    PubMed

    Vakil, Kairav; Minami, Elina; Fishbein, Daniel P

    2014-04-01

    A 55-year-old woman with a history of complete heart block, atrial flutter, and progressive right ventricular failure was referred to our tertiary care center to be evaluated for cardiac transplantation. The patient's clinical course included worsening right ventricular dysfunction for 3 years before the current evaluation. Our clinical findings raised concerns about arrhythmogenic right ventricular cardiomyopathy. Noninvasive imaging, including a positron emission tomographic scan, did not reveal obvious myocardial pathologic conditions. Given the end-stage nature of the patient's right ventricular failure and her dependence on inotropic agents, she underwent urgent listing and subsequent heart transplantation. Pathologic examination of the explanted heart revealed isolated right ventricular sarcoidosis with replacement fibrosis. Biopsy samples of the cardiac allograft 6 months after transplantation showed no recurrence of sarcoidosis. This atypical presentation of isolated cardiac sarcoidosis posed a considerable diagnostic challenge. In addition to discussing the patient's case, we review the relevant medical literature and discuss the need for updated differential diagnostic criteria for end-stage right ventricular failure that mimics arrhythmogenic right ventricular cardiomyopathy.

  5. A case of isolated sacral and pelvic sarcoidosis diagnosed by bone marrow biopsy.

    PubMed

    Garwood, Amy S; Mikuls, Ted R

    2003-10-01

    Although sarcoidosis frequently involves bone, it rarely presents as isolated osseous disease. We present a case in which sarcoidosis is limited to the sacrum and pelvis, a case that underscores the potential importance of both magnetic resonance imaging (MRI) and bone marrow biopsy in establishing the diagnosis. Additionally, we report the interval resolution of bony disease by MRI following glucocorticoid treatment.

  6. Risk of fragility fracture among patients with sarcoidosis: a population-based study 1976-2013.

    PubMed

    Ungprasert, P; Crowson, C S; Matteson, E L

    2017-02-16

    Incidence of fragility fracture of a population-based cohort of 345 patients with sarcoidosis was compared with age and sex-matched comparators. The incidence of fragility fracture was higher among patients with sarcoidosis with hazard ratio (HR) of 2.18.

  7. Lesion of a lower lip scar--an initial presentation of sarcoidosis.

    PubMed

    Ribeiro de Castro, Maria Cristina; Maya, Tullia Cuzzi; Pereira, Lea Freitas; Lugon, Nilza Viana; Ramos-e-Silva, Marcia

    2002-09-01

    The development of sarcoidosis at the site of previous scar is unusual and may be the first sign of systemic disease. Sarcoidosis on a lower lip scar persisting for 13 years, which pointed to examination for internal manifestations, is presented along with a review of the subject

  8. The diagnosis of sarcoidosis pleurisy by medical thoracoscopy: report of three cases.

    PubMed

    Akçay, Sule; Pinelli, Valentina; Marchetti, Gian Pietro; Tassi, Gian Franco

    2008-01-01

    Pleural effusion in sarcoidosis is infrequent. The data on thoracoscopic observations of sarcoidosis pleurisy are limited. The present study describes three cases of sarcoid-related pleurisy diagnosed by medical thoracoscopy and discusses the thoracoscopic features of sarcoid pleuritis. The appearance of pleural nodules was completely different in the three cases, and the distribution of nodules of sarcoidosis was heterogenously located in the pleural surfaces. Pleural disease in sarcoidosis could be proved easily by sampling visible nodules, and pleural fluid could be aspirated without complications during thoracoscopy. Due to symptomatic pleurisy of sarcoidosis, therapy was given as systemic corticosteroid. In conclusion, thoracoscopy may be an appropriate alternative technique to obtain an accurate diagnosis in sarcoid pleurisy.

  9. Sarcoidosis vs. Sarcoid-like reactions: The Two Sides of the same Coin?

    PubMed

    Tchernev, Georgi; Tana, Claudio; Schiavone, Cosima; Cardoso, José-Carlos; Ananiev, Julian; Wollina, Uwe

    2014-07-01

    Differentiating between sarcoidosis as an autonomous disease and sarcoid-like reactions requires considerable efforts. The epithelioid cell granuloma is not equivalent to sarcoidosis because it may be identified in a number of infectious and noninfectious disorders, including neoplastic diseases. At the current state of knowledge, accurate distinction between different causes of epithelioid cell granulomas is in many cases not possible. Despite being characteristic of sarcoidosis and sarcoid-like reactions, the epithelioid cell granuloma is not their synonym, as numerous other causes can give rise to such a type of granulomatous infiltrate. Its etiology should be sought through careful additional investigations, including the genetic signature of both conditions.Sarcoid-like reactions may be grouped generally into several subtypes. The differentiation between each one of them requires a certain combination of diagnostic tests. The major objective of these tests is to exclude or to prove the presence of an infectious, tumoral, or immunogenic antigen on the one hand, and to characterize the genetic profile of the affected patients (for example, sarcoidosis-specific genes) on the other. Only thus may one accurately differentiate between the two pathologic conditions described earlier in the abstract.The clear differentiation between sarcoidosis as a separate disease and sarcoid-like pathologies leads to the more precise clarification of the final diagnosis, which may in turn allow for a more appropriate therapy and improvement in the quality of life of the patients. Equating sarcoid granulomas with sarcoidosis can lead to serious consequences in a number of patients. Sadly enough, after scrutinizing the current available data in the world literature, one cannot find criteria to allow such distinction in a high percentage of the investigated cases.This critical review provides a completely new pathogenetic and diagnostic algorithm, helping in the differentiation

  10. Tadalafil therapy for sarcoidosis-associated pulmonary hypertension

    PubMed Central

    Baughman, R. P.; Aris, R.; Engel, P.; Donohue, J. F.

    2016-01-01

    Abstract Sarcoidosis-associated pulmonary hypertension (SAPH) is estimated to occur in at least 5% or more of sarcoidosis patients, and it contributes to significant morbidity and mortality. Optimal therapy for SAPH is not well established. We performed a 24-week open-label trial of tadalafil for SAPH at 2 academic medical centers. Subjects were required to have confirmed sarcoidosis plus a right heart catheterization within 12 months of enrollment showing a mean pulmonary artery pressure ≥ 25 mmHg, a pulmonary artery wedge pressure ≤ 15 mmHg, and a calculated pulmonary vascular resistance ≥ 3 Wood units. Subjects received 20 mg/day of tadalafil for the first 4 weeks and then 40 mg/day for the subsequent 20 weeks. Sixteen patients were screened, 12 of whom met criteria for enrollment. At 24 weeks, there was no overall improvement in 6-minute walk distance (6MWD). Five of the 12 subjects dropped out of the study early (2 for social reasons, 3 for medical reasons). There was no significant change in short form 36, St. George’s respiratory questionnaire, or maximum Borg dyspnea scores over the 24 weeks. There were no significant adverse events or laboratory abnormalities clearly related to tadalafil in the cohort. The study did not meet the primary end point of change in 6MWD because of the small sample size. Tadalafil was generally safely administered in this cohort of SAPH patients. There was a relatively high dropout rate but no major adverse events and no clinical worsening. Larger studies are needed to explore this question further. (Trial registration: ClinicalTrials.gov identifier: NCT01324999) PMID:28090299

  11. Mechanisms of Physical Activity Limitation in Chronic Lung Diseases

    PubMed Central

    Vogiatzis, Ioannis; Zakynthinos, George; Andrianopoulos, Vasileios

    2012-01-01

    In chronic lung diseases physical activity limitation is multifactorial involving respiratory, hemodynamic, and peripheral muscle abnormalities. The mechanisms of limitation discussed in this paper relate to (i) the imbalance between ventilatory capacity and demand, (ii) the imbalance between energy demand and supply to working respiratory and peripheral muscles, and (iii) the factors that induce peripheral muscle dysfunction. In practice, intolerable exertional symptoms (i.e., dyspnea) and/or leg discomfort are the main symptoms that limit physical performance in patients with chronic lung diseases. Furthermore, the reduced capacity for physical work and the adoption of a sedentary lifestyle, in an attempt to avoid breathlessness upon physical exertion, cause profound muscle deconditioning which in turn leads to disability and loss of functional independence. Accordingly, physical inactivity is an important component of worsening the patients' quality of life and contributes importantly to poor prognosis. Identifying the factors which prevent a patient with lung disease to easily carry out activities of daily living provides a unique as well as important perspective for the choice of the appropriate therapeutic strategy. PMID:23365738

  12. Dermoscopy could be useful in differentiating sarcoidosis from necrobiotic granulomas even after treatment with systemic steroids

    PubMed Central

    Ramadan, Shahira; Hossam, Dalia; Saleh, Marwah A.

    2016-01-01

    Background: Diagnosing cutaneous sarcoidosis and necrobiotic granulomas is challenging. Objective: Assessing the value of dermoscopy in differentiating cutaneous sarcoidosis from necrobiotic granulomas and evaluating whether their dermoscopic features will be altered after treatment. Methods: Nineteen cutaneous sarcoidosis and 11 necrobiotic granuloma patients (2 necrobiosis lipoidica, 4 granuloma annulare and 5 rheumatoid nodule) were included in this study. The diagnosis was confirmed by skin biopsy. The lesions were examined using non-contact polarized dermoscope (Dermlite 2 HR-Pro; 3Gen, San Juan Capistrano, CA). Results: Ten out of 19 cutaneous sarcoidosis patients and 7/11 necrobiotic cases group were receiving treatments (topical, intralesional or systemic steroids ± chloroquine) but still have cutaneous lesions. Treatment duration in the sarcoidosis group ranged from 2 months to 10 years (median 3 years) and in the necrobiotic cases group ranged from 3 months to 16 years (median 2 years). Pink homogenous background, translucent orange areas, white scar-like depigmentation and fine white scales were significantly associated with the cutaneous sarcoidosis compared to necrobiotic cases group. On the other hand mixed pink, white and yellowish background was significantly associated with the necrobiotic cases group. No significant difference in the dermoscopic findings was detected between treated and non-treated patients. Conclusion: Some dermoscopic findings are shared between the cutaneous sarcoidosis group and the necrobiotic cases group, yet dermoscopy could be a useful aid in differentiating them even after treatment. PMID:27648379

  13. WHOQOL-bREF questionnaire as a measure of quality of life in sarcoidosis.

    PubMed

    Alilović, Marija; Peros-Golubicić, Tatjana; Radosević-Vidacek, Biserka; Koscec, Adrijana; Tekavec-Trkanjec, Jasna; Solak, Mirsala; Hećimović, Ana; Smojver-Jezek, Silvana

    2013-09-01

    The aim of this study was to evaluate the usefulness of a short form of the WHOQOL questionnaire, the WHOQOL-BREF, which consists of 24 questions, in evaluating quality of life (QOL) in sarcoidosis patients. A group of 97 sarcoidosis patients and a matched group of 97 healthy controls took part in the study. Their QOL was examined by means of the WHOQOL-BREF, and the respiratory functions were measured in sarcoidosis patients. The WHOQOL-BREF revealed significantly poorer QOL of sarcoidosis patients in the domains of Physical and Psychological Health in comparison to healthy controls. In contrast, sarcoidosis patients perceived their QOL significantly better than healthy controls in the domains of Social Relations and Environment. Differences between sarcoidosis patients and healthy controls were found in several items from the WHOQOL-BREF and some of them were modified by gender. However, the WHOQOL-BREF did not prove to be a sensitive measure of fatigue, which is the most common symptom in sarcoidosis patients.

  14. [Educational activities for people with chronic disease: grants for nursing].

    PubMed

    Ulbrich, Elis Martins; Maftum, Mariluci Alves; Labronici, Liliana Maria; Mantovani, Maria de Fátima

    2012-06-01

    This is an intervention study conducted in a Unidade Básica de Saúde (Basic Health Unit) in Colombo, Parana, Brazil from March to November 2009, with 35 carriers of chronic diseases aged between 18 and 60 years, and enrolled in the Hypertension and Diabetes Program. The objectives were to identify their knowledge about arterial hypertension and act through educational group activities. Data were collected though semistructured interviews and four group meetings, and the following categories emerged from the analysis: "Understanding of the disease" and "Ways of caring". It was found that users knew the disease, its risk factors and possible complications, and that educational activities favored the sharing of experiences,provided reflection and the possibility of treatment management. This is a strategy that should be used and promoted by nurses.

  15. Alternatively activated macrophages promote pancreatic fibrosis in chronic pancreatitis

    PubMed Central

    Xue, Jing; Sharma, Vishal; Hsieh, Michael H.; Chawla, Ajay; Murali, Ramachandran; Pandol, Stephen J.; Habtezion, Aida

    2015-01-01

    Chronic pancreatitis (CP) is a progressive and irreversible inflammatory and fibrotic disease with no cure. Unlike acute pancreatitis, we find that alternatively activated macrophages (AAMs) are dominant in mouse and human CP. AAMs are dependent on IL-4 and IL-13 signaling and we show that mice lacking IL-4Rα, myeloid specific IL-4Rα, and IL-4/IL-13 were less susceptible to pancreatic fibrosis. Furthermore, we demonstrate that mouse and human pancreatic stellate cells (PSCs) are a source of IL-4/IL-13. Notably, we show that pharmacologic inhibition of IL-4/IL-13 in human ex-vivo studies as well as in established mouse CP decreases pancreatic AAMs and fibrosis. We identify a critical role for macrophages in pancreatic fibrosis and in turn PSCs as important inducers of macrophage alternative activation. Our study challenges and identifies pathways involved in cross talk between macrophages and PSCs that can be targeted to reverse or halt pancreatic fibrosis progression. PMID:25981357

  16. NLRP3 Inflammasome Activation in Dialyzed Chronic Kidney Disease Patients

    PubMed Central

    Granata, Simona; Masola, Valentina; Zoratti, Elisa; Scupoli, Maria Teresa; Baruzzi, Anna; Messa, Michele; Sallustio, Fabio; Gesualdo, Loreto; Lupo, Antonio; Zaza, Gianluigi

    2015-01-01

    To assess whether NLR pyrin domain-containing protein 3 (NLRP3) inflammasome, a multiprotein complex that mediates the activation of caspase-1 (CASP-1) and pro-inflammatory cytokines IL-18 and IL-1β, could be involved in the chronic inflammatory state observed in chronic kidney disease patients undergoing hemodialysis treatment (CKD-HD), we employed several biomolecular techniques including RT-PCR, western blot, FACS analysis, confocal microscopy and microarray. Interestingly, peripheral blood mononuclear cells from 15 CKD-HD patients showed higher mRNA levels of NLRP3, CASP-1, ASC, IL-1β, IL-18 and P2X7receptor compared to 15 healthy subjects. Western blotting analysis confirmed the above results. In particular, active forms of CASP-1, IL1-β and IL-18 resulted significantly up-regulated in CKD-HD versus controls. Additionally, elevated mitochondrial ROS level, colocalization of NLRP3/ASC/mitochondria in peripheral blood mononuclear cells from CKD-HD patients and down-regulation of CASP-1, IL1-β and IL-18 protein levels in immune-cells of CKD-HD patients stimulated with LPS/ATP in presence of mitoTEMPO, inhibitor of mitochondrial ROS production, suggested a possible role of this organelle in the aforementioned CKD-associated inflammasome activation. Then, microarray analysis confirmed, in an independent microarray study cohort, that NLRP3 and CASP-1, along with other inflammasome-related genes, were up-regulated in 17 CKD-HD patients and they were able to clearly discriminate these patients from 5 healthy subjects. All together these data showed, for the first time, that NLRP3 inflammasome was activated in uremic patients undergoing dialysis treatment and they suggested that this unphysiological condition could be possibly induced by mitochondrial dysfunction. PMID:25798846

  17. Cigarette smoking and male sex are independent and age concomitant risk factors for the development of ocular sarcoidosis in a new orleans sarcoidosis population

    PubMed Central

    Janot, Adam C.; Huscher, Dörte; Walker, McCall; Grewal, Harmanjot K.; Yu, Mary; Lammi, Matthew R.; Saketkoo, Lesley Ann

    2016-01-01

    Introduction Sarcoidosis is a multi-organ system granulomatous disease of unknown origin with an incidence of 1–40/100,000. Though pulmonary manifestations are predominant, ocular sarcoidosis (OS) affects 25–50% of patients with sarcoidosis and can lead to blindness. Methods A retrospective, single-center chart review of sarcoidosis cases investigated variables associated with the development of OS. Inclusion criteria were biopsy-proven sarcoidosis, disease duration greater than 1 year, documented smoking status on chart review and documentation of sarcoid-related eye disease. Multivariate analysis identified independent risk factors for OS. Results Of 269 charts reviewed, 109 patients met inclusion criteria. The OS group had a significantly higher proportion of smokers (71.4%) than without OS (42.0%, p=0.027) with no difference (p=0.61) in median number of pack years. Male sex was significantly higher in the OS group (57.1% versus 26.1%, p=0.009). Median duration of sarcoidosis was higher in the OS group (10 versus 4 years, p=0.031). Multivariate regression identified tobacco exposure (OR=5.25, p=0.007, 95% CI 1.58–17.41), male sex (OR=7.48, p=0.002, 95% CI 2.15–26.01), and age (OR=1.114, p=0.002, 95% CI 1.04–1.19) as concomitant risk factors for the development of OS. Conclusion To date, there are few dedicated investigations of risk factors for OS, especially smoking. This investigation identified male sex, age, and tobacco exposure as independent risk factors for OS. Though disease duration did not withstand regression analysis in this moderately sized group, age at chart review suggests screening for OS should not remit but rather intensify in aging patients with sarcoidosis. PMID:26278693

  18. A granulomatous conundrum: Concurrent necrobiosis lipoidica, cutaneous sarcoidosis and erythema nodosum in a nondiabetic patient.

    PubMed

    Valecha, Nishant; Bennett, Genevieve; Yip, Leona

    2017-02-17

    Necrobiosis lipoidica (NL) and cutaneous sarcoidosis are granulomatous disorders with a largely unknown aetiopathogenesis. Evidence of co-existing NL and sarcoidosis in the same patient may suggest a degree of overlap between these entities through shared granulomatous inflammatory pathways. Occasionally, one condition can mimic the other, making their distinction difficult. We report a novel case of a non-diabetic woman who presented with concurrent NL, cutaneous sarcoidosis and erythema nodosum. We discuss some of the complexities distinguishing these entities and propose that they may represent different stages of the same granulomatous process linked through yet unknown pathomechanisms.

  19. Exacerbation of recalcitrant cutaneous sarcoidosis with adalimumab - a paradoxical effect? A case report*

    PubMed Central

    Santos, Guida; Sousa, Lourdes Emerenciano; João, Alexandre Miguel Bruno Lopes

    2013-01-01

    The paradoxical adverse effects of tumor necrosis factor-alpha (TNF-alpha) antagonists have been described frequently as a result of the widespread use of these drugs. Among the TNF-alpha blocking agents, few reports exist relating the use of adalimumab in cutaneous sarcoidosis, although all of them show good results. More recently, sarcoidosis onsets have been reported with various TNF-alpha inhibitors. The current case is, to our knowledge, the first to describe the exacerbation of cutaneous lesions of sarcoidosis treated with adalimumab. PMID:24346872

  20. Overcoming the Influence of Chronic Pain on Older Patients' Difficulty with Recommended Self-Management Activities

    ERIC Educational Resources Information Center

    Krein, Sarah L.; Heisler, Michele; Piette, John D.; Butchart, Amy; Kerr, Eve A.

    2007-01-01

    Purpose: Many older patients with common chronic conditions also experience chronic pain. We examined how chronic pain affects patients' difficulty with recommended self-management activities and the potential intervening role of self-efficacy (the level of confidence in one's own ability to perform a specific task). Design and Methods: We…

  1. Cardiac actomyosin ATPase activity after chronic doxorubicin treatment.

    PubMed

    Bergson, A; Inchiosa, M A

    1985-04-01

    Doxorubicin (Adriamycin), a potent antineoplastic drug, produces progressive cardiotoxicity which may lead to ultimate cardiac failure. The effects of chronic doxorubicin treatment on cardiac actomyosin ATPase were the principal focus of the present studies. This approach was based on the established correlation between cardiac contractility and contractile protein ATPase activity. Rabbits were injected intravenously with doxorubicin (4 mg/kg) at weekly intervals for 1-7 weeks. Body weight increase was attenuated in the treated animals; heart weight/body weight ratio was unchanged. Actomyosin and water contents of ventricular muscle were not different in doxorubicin-treated as compared with vehicle control animals. Cellular damage was detected histologically after one dose of doxorubicin (equivalent to a single clinical dose), and was extensive after 4-5 weeks of treatment. Animals which received 1-2 injections of doxorubicin demonstrated a 29% average increase in actomyosin ATPase activity as compared to vehicle controls; this difference was highly significant (p less than 0.001). Further treatment with doxorubicin tended to progressively decrease ATPase activity. It is suggested that the increased actomyosin ATPase activity seen with low total doses of doxorubicin may represent a compensatory mechanism for maintenance of contractility; this interpretation is supported by the clinical observation that the morphologic evidence of progressive doxorubicin toxicity is not associated with a parallel decrease in contractility, until severe cumulative toxicity has been induced.

  2. Physical activity, by enhancing parasympathetic tone and activating the cholinergic anti-inflammatory pathway, is a therapeutic strategy to restrain chronic inflammation and prevent many chronic diseases.

    PubMed

    Lujan, Heidi L; DiCarlo, Stephen E

    2013-05-01

    Chronic diseases are the leading cause of death in the world and chronic inflammation is a key contributor to many chronic diseases. Accordingly, interventions that reduce inflammation may be effective in treating multiple adverse chronic conditions. In this context, physical activity is documented to reduce systemic low-grade inflammation and is acknowledged as an anti-inflammatory intervention. Furthermore, physically active individuals are at a lower risk of developing chronic diseases. However the mechanisms mediating this anti-inflammatory phenotype and range of health benefits are unknown. We hypothesize that the "cholinergic anti-inflammatory pathway" (CAP) mediates the anti-inflammatory phenotype and range of health benefits associated with physical activity. The CAP is an endogenous, physiological mechanism by which acetylcholine from the vagus nerve, interacts with the innate immune system to modulate and restrain the inflammatory cascade. Importantly, higher levels of physical activity are associated with enhanced parasympathetic (vagal) tone and lower levels of C-reactive protein, a marker of low-grade inflammation. Accordingly, physical activity, by enhancing parasympathetic tone and activating the CAP, may be a therapeutic strategy to restrain chronic inflammation and prevent many chronic diseases.

  3. [A case of lichenoid sarcoidosis with characteristic clinical and histopathological findings].

    PubMed

    Sanchez-Lopez, Josefa; Porriño-Bustamante, Ma Librada; Aneiros-Fernández, Jose; Naranjo-Sintes, Ramon; Fernández-Pugnaire, Ma Antonia

    2014-04-16

    Sarcoidosis is a multisystem inflammatory disease characterized by the formation of noncaseating granulomas in various organs and tissues. The majority of patients with systemic sarcoidosis will present with lung and lymph node involvement. In addition, 20% have skin involvement that may be the only manifestation of the disease or may be an important prognostic marker for involvement of other organs. There are multiple forms of presentation of cutaneous sarcoidosis, which may be a true challenge.We report a patient with a one month history of an eruption of skin colored papules. Some were grouped in a symmetrical distribution on the trunk, inner arms, and lumbar region. Pathologic examination revealed an infiltrate in the papillary dermis showing a band of noncaseating granulomas along with disruption of the basal lamina and lichenoid changes. The clinicopathological correlation confirmed the diagnosis of lichenoid sarcoidosis. We consider our case interesting owing to the clinical presentation and the lichenoid distribution of granulomas.

  4. (18)F-fluoromisonidazole (FMISO) PET may have the potential to detect cardiac sarcoidosis.

    PubMed

    Manabe, Osamu; Hirata, Kenji; Shozo, Okamoto; Shiga, Tohru; Uchiyama, Yuko; Kobayashi, Kentaro; Watanabe, Shiro; Toyonaga, Takuya; Kikuchi, Hisaya; Oyama-Manabe, Noriko; Tamaki, Nagara

    2017-02-01

    (18)F-fluoromisonidazole (FMISO) is a positron emission tomography (PET) tracer that accumulates in hypoxic tissues. We here present a case of suspected cardiac sarcoidosis which was detected with increased FMISO uptake.

  5. Multiple bilateral pulmonary nodules masquerading as pulmonary metastasis; a case of nodular sarcoidosis

    PubMed Central

    Jafari, Mostafa; Farrokh, Donya; Mohammadpanah, Najmeh

    2016-01-01

    Sarcoidosis is a multi-system inflammatory disorder of unknown etiology that is manifested by the presence of non-caseating granulomas. Multiple pulmonary nodules are rare presentations of sarcoidosis. We report a case of nodular sarcoidosis in a young male of Middle-East origin who had initially presented with bilateral painful ankle edema. His chest X-ray showed multiple bilateral pulmonary nodules. A high resolution computed tomography scan of the chest demonstrated multiple pulmonary nodular lesions and also mediastinal and hilar lymphadenopathy. Subsequent biopsies revealed non-necrotizing granuloma with multi-nucleated giant cells indicative of sarcoidosis. An appropriate work-up was done to confirm the true nature of the nodules and facilitate treatment. PMID:27757192

  6. Basophil Activation Test identifies the patients with Chronic Spontaneous Urticaria suffering the most active disease

    PubMed Central

    Curto‐Barredo, Laia; Yelamos, Jose; Gimeno, Ramon; Mojal, Sergi; Pujol, Ramon M.

    2016-01-01

    Abstract Introduction The basophil activation test showing CD63 up regulation could be a specific and sensitive in vitro complementary text to the in vivo autologous serum skin test for the activity assessment of the patients suffering autoimmune chronic spontaneous urticaria. The aim of this study is to define the basophil activation test as a useful tool in clinical practice in order to identify those patients with more active disease. Methods We screened 139 patients (96 women) diagnosed of chronic spontaneous urticaria using simultaneously autologous serum skin test and basophil activation test and their relationship with disease activity. Results Positive autologous serum skin test was found in 56.8%; from them, 31.6% were basophil activation test positive. Negative autologous serum skin test result was found in the 43.2% of the sample that showed negative CD63 expression results in all cases, except one. Patients with positive autologous serum skin test and positive CD63 by basophil activation test showed significant higher Urticaria Activity Score of 7 days (P = 0.004) and of 3 weeks (P = 0.001) than patients with positive autologous serum skin test and negative CD63 (mean ± standard deviation [SD] 26.57 ± 10.56 versus 18.40 ± 12.05 for the Urticaria Activity Score of 7 days and 56.47 ± 23.78 versus 39.88 ± 25.44 for the Urticaria Activity Score of 3 weeks). Conclusions The CD63 expression on basophils appears as a reliable in vitro marker, useful in clinical practice in combination with autologous serum skin test to define chronic spontaneous urticaria patients with the highest urticaria activity that impairs a normal life. PMID:27980778

  7. Proteomic Analysis of Kveim Reagent Identifies Targets of Cellular Immunity in Sarcoidosis

    PubMed Central

    Parker, Robert; Siddiqui, Nazneen; Potiphar, Lee; Goldin, Rob; Timms, John F.; Wells, Athol U.; Kon, Onn M.; Wickremasinghe, Melissa; Mitchell, Donald; Weeks, Mark E.; Lalvani, Ajit

    2017-01-01

    Background Kveim-reagent (Kv) skin testing was a historical method of diagnosing sarcoidosis. Intradermal injection of treated sarcoidosis spleen tissue resulted in a granuloma response at injection site by 4–6 weeks. Previous work indicates proteins as the possible trigger of this reaction. We aimed to identify Kv-specific proteins and characterise the ex vivo response of Peripheral Blood Mononuclear Cells (PBMCs) from sarcoidosis, tuberculosis and healthy control patients when stimulated with both Kv and selected Kv-specific proteins. Methods Kv extracts were separated by 1D-SDS-PAGE and 2D-DIGE and then underwent mass spectrometric analysis for protein identification. Sarcoidosis and control PBMCs were first stimulated with Kv and then with three selected recombinant protein candidates which were identified from the proteomic analysis. PBMC secreted cytokines were subsequently measured by Multiplex Cytokine Assay. Results We observed significantly increased IFN-γ and TNF-α secretion from Kv-stimulated PBMCs of sarcoidosis patients vs. PBMCs from healthy volunteers (IFN-γ: 207.2 pg/mL vs. 3.86 pg/mL, p = 0.0018; TNF-α: 2375 pg/mL vs. 42.82 pg/mL, p = 0.0003). Through proteomic approaches we then identified 74 sarcoidosis tissue-specific proteins. Of these, 3 proteins (vimentin, tubulin and alpha-actinin-4) were identified using both 1D-SDS-PAGE and 2D-DIGE. Data are available via ProteomeXchange with identifier PXD005150. Increased cytokine secretion was subsequently observed with vimentin stimulation of sarcoidosis PBMCs vs. tuberculosis PBMCs (IFN-γ: 396.6 pg/mL vs 0.1 pg/mL, p = 0.0009; TNF-α: 1139 pg/mL vs 0.1 pg/mL, p<0.0001). This finding was also observed in vimentin stimulation of sarcoidosis PBMCs compared to PBMCs from healthy controls (IFN-γ: 396.6 pg/mL vs. 0.1 pg/mL, p = 0.014; TNF-α: 1139 pg/mL vs 42.29 pg/mL, p = 0.027). No difference was found in cytokine secretion between sarcoidosis and control PBMCs when stimulated with either tubulin

  8. Physical Activity and Hemodynamic Reactivity in Chronic Kidney Disease

    PubMed Central

    Agarwal, Rajiv; Light, Robert P.

    2008-01-01

    Background and objectives: Patients with chronic kidney disease (CKD) have an elevated cardiovascular risk. This study was designed to understand better the presence and strength of the relationship between physical activity and BP and to explore determinants of hemodynamic reactivity. Design, setting, participants, & measurements: Twenty-four patients with CKD (mean age 69.5 yr; 3.1 antihypertensive drugs; estimated GFR 47 ml/min per 1.73 m2, albumin/creatinine ratio 403 mg/g) were studied on three occasions during a 6-wk period with 24-h ambulatory BP monitoring and simultaneous activity monitoring with wrist actigraphy. Results: Nondippers were found have a greater level of sleep activity compared with dippers, although the awake activity level was similar (7.06 versus 6.73) between groups (P = 0.042 for interaction). In 3587 BP activity pairs, hemodynamic reactivity was variable between individuals (systolic BP reactivity 1.06 [SD 10.50]; diastolic BP reactivity 0.89 [SD 7.80] heart rate reactivity 1.18 [SD 11.00]); those who were more sedentary had a greater increment in systolic BP compared with those who were less sedentary. Antihypertensive drugs blunted hemodynamic reactivity. Hemodynamic reactivity was greatest between 12 a.m. and 8 a.m., making this a vulnerable period for cardiovascular events. Conclusions: Greater hemodynamic reactivity in sedentary people with CKD offers a possible and thus far unrecognized mechanism of cardiovascular damage. Besides reducing BP, antihypertensive drugs reduce hemodynamic reactivity, which offers another plausible mechanism of cardiovascular protection with their use. PMID:18922983

  9. Mediastinal sarcoidosis mimicking lymph malignancy recurrence after anti-neoplastic therapy.

    PubMed

    El Hammoumi, Massine; El Marjany, Mohamed; Moussaoui, Driss; Doudouh, Aberahim; Mansouri, Hamid; Kabiri, El Hassane

    2015-07-01

    The aim of our work is to promote the awareness about the development of sarcoidosis after antineoplastic therapy in order to avoid diagnostic errors with FDG-PET/CT findings. We report the observation of three women with breast, cervix and stomach treated cancers who developed a sarcoidosis after the end of anti-neoplastic therapy. The utility of FDG-PET/CT is in pinpointing the organs candidates for diagnostic biopsy and not distinguishing between the malignancy and granulomatous or inflammatory diseases.

  10. Chronic pain management in the active-duty military

    NASA Astrophysics Data System (ADS)

    Jamison, David; Cohen, Steven P.

    2012-06-01

    As in the general population, chronic pain is a prevalent and burdensome affliction in active-duty military personnel. Painful conditions in military members can be categorized broadly in terms of whether they arise directly from combat injuries (gunshot, fragmentation wound, blast impact) or whether they result from non-combat injuries (sprains, herniated discs, motor vehicle accidents). Both combat-related and non-combat-related causes of pain can further be classified as either acute or chronic. Here we discuss the state of pain management as it relates to the military population in both deployed and non-deployed settings. The term non-battle injury (NBI) is commonly used to refer to those conditions not directly associated with the combat actions of war. In the history of warfare, NBI have far outstripped battle-related injuries in terms not only of morbidity, but also mortality. It was not until improvements in health care and field medicine were applied in World War I that battle-related deaths finally outnumbered those attributed to disease and pestilence. However, NBI have been the leading cause of morbidity and hospital admission in every major conflict since the Korean War. Pain remains a leading cause of presentation to military medical facilities, both in and out of theater. The absence of pain services is associated with a low return-to-duty rate among the deployed population. The most common pain complaints involve the low-back and neck, and studies have suggested that earlier treatment is associated with more significant improvement and a higher return to duty rate. It is recognized that military medicine is often at the forefront of medical innovation, and that many fields of medicine have reaped benefit from the conduct of war.

  11. Polycystic Liver Disease and Sarcoidosis: Unusual Coexisting Etiologies of Portal Hypertension

    PubMed Central

    Jagroop, Sophia; Parthvi, Rukma

    2017-01-01

    Both polycystic liver disease (PLD) and sarcoidosis can involve liver. Most of the time, liver disease in both conditions is asymptomatic, but they can rarely cause portal hypertension. Our aim is to report a case of a 51-year-old female with a history of adult dominant polycystic kidney disease (ADPKD) and sarcoidosis who presented with multiple episodes of hematemesis. An endoscopy showed grade 3 esophageal varices. A computed tomography (CT) scan of the abdomen showed ascites with polycystic liver, nodular contour, and calcified granuloma. PLD can cause portal hypertension due to fibrosis or large cysts compressing on the portal vein. On the other hand, sarcoidosis causes portal hypertension by formation of arteriovenous(AV) shunts or fibrosis in areas of granulomas. Both conditions are diagnosed on imaging. There is no approved medical treatment for PLD; the only curative treatment is liver transplantation. Asymptomatic hepatic sarcoidosis does not need any treatment. The recommended treatment is corticosteroids for both isolated and systemic sarcoidosis. ADPKD and sarcoidosis can involve multiple organs. The presence of both conditions can accelerate the disease process and could be a therapeutic challenge. Early abdominal imaging during the course of both diseases can improve the outcome by decreasing the diagnostic window. PMID:28280650

  12. [Cryptococcal meningitis in a patient with a ventriculoperitoneal shunt and monitoring for pulmonary sarcoidosis].

    PubMed

    Baallal, H; El Asri, A C; Eljebbouri, B; Akhaddar, A; Gazzaz, M; El Mostarchid, B; Boucetta, M

    2013-02-01

    The fungus Cryptococcus neoformans can cause common opportunistic infection in acquired immune deficiency syndrome (AIDS) patients. But other conditions can be associated with sarcoidosis. Meningoencephalitis is the most common manifestation of this disease. One of the most important neurological complications is the development of intracranial hypertension (ICH), which may result in high morbidity and mortality. We report the case of a patient harboring a ventriculoperitoneal shunt, and having contracted a cryptococcal meningitis as a risk factor for pulmonary sarcoidosis. Brain MRI showed arachnoiditis, with a mass in contact with the right frontal horn. Indian ink staining of the cerebrospinal fluid (CSF) showed positivity that was confirmed by the identification of Cryptococcus neoformans after culture. The evolution was favorable under medical treatment with removal of material. The relationship between sarcoidosis and cryptococcosis, described in the literature is not coincidental but is a rare complication of sarcoidosis of potential severity (40% of mortality). Sarcoidosis is a common systemic disease that may increase host susceptibility to CNS cryptococcal infection without any other signs or symptoms of host immunosuppression. The diagnosis of cryptococcosis should be evoked as a differential diagnosis of neuro-sarcoidosis.

  13. Scar sarcoidosis on a finger mimicking a rapidly growing soft tissue tumour: a case report

    PubMed Central

    2012-01-01

    Background Scar sarcoidosis is a rare and uncommon but specific cutaneous manifestation of sarcoidosis. In general it arises in pre-existing scars deriving from mechanical traumas. As most surgeons dealing with scars might not be aware of cutaneous sarcoidosis and its different types of appearance the appropriate staging and treatment might be missed or at least delayed. To our knowledge this is the first case in literature of scar sarcoidosis on a finger. Case presentation We present a case of a 33-year-old carpenter who developed scar sarcoidosis on his right index finger 4 years after the tendon of the long digital flexor got accidentally cut by an angle grinder. He was referred due to a swelling of the finger suspected to be a malignant soft tissue tumour. The circumference of the affected finger had almost doubled, adding up to 94 mm. Incision biopsy revealed typical noncaseating granulomas. Further investigation showed a systemic extent of the disease with involvement of the lung. A systemic treatment with oral steroids led to an almost full regression of the swelling with restoration of function and resolution of lung infiltrates. Conclusion In case of a suspicious and/or progressive swelling a definite diagnosis should be achieved by biopsy within a short time to enable a proper treatment. If scar sarcoidosis is proven further investigation is necessary to exclude a systemical involvement. A surgical treatment of the swelling is not indicated. PMID:23031186

  14. Vitreous lavage fluid and bronchoalveolar lavage fluid have equal diagnostic value in sarcoidosis

    PubMed Central

    Maruyama, Kazuichi; Inaba, Tohru; Tamada, Tsutomu; Nakazawa, Toru

    2016-01-01

    Abstract Here, we elucidate the immunological features of both bronchoalveolar lavage fluid (BALF) and vitreous lavage fluid (VLF) samples from patients with histopathologically verified sarcoidosis. In addition, we assess the safety of vitrectomy in sarcoidosis patients by investigating the occurrence of complications and the recovery of visual acuity. Twenty-two eyes of 22 patients with tissue-proven sarcoidosis were enrolled in this study. BALF and VLF samples were obtained and compared in each patient, and the clinical course (including visual acuity) was followed. The presence of sarcoidosis was assessed with a flow cytometric analysis of T-lymphocytes in the BALF and VLF samples. Our results indicated that the CD4 T-cell population and the CD4/CD8 ratio were significantly higher in the VLF T-lymphocytes than the BALF T-lymphocytes. On the other hand, the CD8+ T-cell population was significantly lower in the VLF T-lymphocytes. Therefore, our findings suggest that VLF samples have a high diagnostic value (equal to that of BALF samples) for sarcoidosis. Moreover, we found that the sample collection did not affect visual acuity and that there were no adverse events after surgery. A flow cytometric analysis of a VLF sample may therefore be a useful adjunct in the diagnosis of sarcoidosis. PMID:27930546

  15. Activation of Corticostriatal Circuitry Relieves Chronic Neuropathic Pain

    PubMed Central

    Lee, Michelle; Manders, Toby R.; Eberle, Sarah E.; Su, Chen; D'amour, James; Yang, Runtao; Lin, Hau Yueh; Deisseroth, Karl; Froemke, Robert C.

    2015-01-01

    Neural circuits that determine the perception and modulation of pain remain poorly understood. The prefrontal cortex (PFC) provides top-down control of sensory and affective processes. While animal and human imaging studies have shown that the PFC is involved in pain regulation, its exact role in pain states remains incompletely understood. A key output target for the PFC is the nucleus accumbens (NAc), an important component of the reward circuitry. Interestingly, recent human imaging studies suggest that the projection from the PFC to the NAc is altered in chronic pain. The function of this corticostriatal projection in pain states, however, is not known. Here we show that optogenetic activation of the PFC produces strong antinociceptive effects in a rat model (spared nerve injury model) of persistent neuropathic pain. PFC activation also reduces the affective symptoms of pain. Furthermore, we show that this pain-relieving function of the PFC is likely mediated by projections to the NAc. Thus, our results support a novel role for corticostriatal circuitry in pain regulation. PMID:25834050

  16. Ventricular tachycardia as the first manifestation of cardiac sarcoidosis

    PubMed Central

    Mehrhof, Felix; Stockburger, Martin; Schuette, Hartwig; Haverkamp, Wilhelm; Dietz, Rainer

    2009-01-01

    The case of a 32-year-old man with sustained ventricular tachycardia and hypotension is described. Following pharmacological treatment the patient switched to a sinus rhythm and was transferred to a university hospital for further diagnostic procedures and treatment. Cardiac catherisation ruled out underlying coronary artery disease, and cardiac MRI as well as echocardiography demonstrated a moderately reduced left ventricular ejection fraction, marked thickening of the interventricular septum and extensive intramural and epicardial infiltration of both ventricles. Endomyocardial biopsies were inconclusive; an implantable cardioverter defibrillator (ICD) was implanted in order to prevent a fatal arrhythmic event. Only repeated lymph node biopsies revealed typical findings of granulomatous disease, which together with the clinical course and the cardiac MRI findings strongly supported cardiac sarcoidosis. A few days after initiation of therapy with corticosteroids, the patient experienced the first of a number of ICD discharges, demanding aggressive anti-arrhythmic treatment regimen for the future. PMID:21686620

  17. Sarcoidosis and Histoplasmosis: Is One a Consequence of the Other? A Case Report and Review of the Literature

    PubMed Central

    Bansal, Anupam; Drewek, Rupali

    2015-01-01

    Sarcoidosis involves abnormal collections of inflammatory cells (granulomas) which may form as nodules in multiple organs. 90% of affected patients have respiratory tract abnormalities. We present a 61-year-old male with sarcoidosis who was admitted for respiratory distress. Fibrosing mediastinitis was seen in the chest computograph. Management was conservative and included steroids, antibiotics, and oxygen therapy. Sarcoidosis and fibrosing mediastinitis are rare. Fibrosing mediastinitis is more commonly seen with histoplasmosis. We explore the clinical similarities between histoplasmosis and sarcoidosis. We also explore the potential cause and effect relationship and workup for each disease entity. PMID:26345350

  18. Acute renal failure as a form of presentation of sarcoidosis in a young adult: a case report

    PubMed Central

    2014-01-01

    Introduction Sarcoidosis is a systemic granulomatous disease. Renal involvement is a rare initial presentation of this disease. Few articles on renal involvement as an initial presentation of sarcoidosis have been published in the literature. Case presentation A 26-year-old Caucasian woman presented with acute renal failure as an initial manifestation of sarcoidosis. Conclusions Renal involvement is an uncommon feature of sarcoidosis and it is essential to establish a fast and correct diagnosis because early therapy avoids progression to terminal renal failure. PMID:25124289

  19. Hepatitis B antigen in hepatocytes of chronic active liver disease.

    PubMed

    Kawanishi, H

    1979-04-01

    To study the morphologic interrelation of hepatocytes with the replication of hepatitis B vius (HBV) and immunocompetent cells in chronic active liver disease(CALD), organ cultures were prepared from liver biopsy specimens. Replication of hepatitis B core antigen (HBcAg) appears to occur in the nucleus of the hepatocyte in close association with intranuclear electron-dense strands and sometimes intranucleolar matrixes (likely HBcAg genomes), and cytoplasmic maturation of the HBcAg takes place in the preautolytic condition of host hepatocytes. Immunocompetent cells became progressively autolyzed in the early period of cultures. No difference in progression of hepatocyte injury in tissues from normal subjects and from hepatitis B surface antigen (HBsAg)-positive and HBsAg-negative patients with CALD may suggest that intracellular synthesis of HBV alone is not cytopathic to host hepatocytes. This model is promising for the study of HBV replication and development, and also for testing the efficacy of new antiviral agents against the virus.

  20. Basophil activation test with food additives in chronic urticaria patients.

    PubMed

    Kang, Min-Gyu; Song, Woo-Jung; Park, Han-Ki; Lim, Kyung-Hwan; Kim, Su-Jung; Lee, Suh-Young; Kim, Sae-Hoon; Cho, Sang-Heon; Min, Kyung-Up; Chang, Yoon-Seok

    2014-01-01

    The role of food additives in chronic urticaria (CU) is still under investigation. In this study, we aimed to explore the association between food additives and CU by using the basophil activation test (BAT). The BAT using 15 common food additives was performed for 15 patients with CU who had a history of recurrent urticarial aggravation following intake of various foods without a definite food-specific IgE. Of the 15 patients studied, two (13.3%) showed positive BAT results for one of the tested food additives. One patient responded to monosodium glutamate, showing 18.7% of CD203c-positive basophils. Another patient showed a positive BAT result to sodium benzoate. Both patients had clinical correlations with the agents, which were partly determined by elimination diets. The present study suggested that at least a small proportion of patients with CU had symptoms associated with food additives. The results may suggest the potential utility of the BAT to identity the role of food additives in CU.

  1. Increased serum cortisol binding in chronic active hepatitis

    SciTech Connect

    Orbach, O.; Schussler, G.C.

    1989-01-01

    A high serum cortisol concentration, apparently due to increased cortisol-binding globulin (CBG), was found in a patient (index case) with chronic active hepatitis (CAH). We therefore performed further studies to determine whether increased cortisol binding is generally associated with CAH. Serum samples were obtained from 15 hospitalized patients with long-term liver function test elevations but no evidence of cirrhosis, 15 normal subjects without a history of hepatitis, four healthy pregnant women, and 10 alcoholic patients with stigmata of cirrhosis. Serum cortisol binding was measured by an adaptation of a previously described charcoal uptake method. Thyroxine-binding globulin (TBG) and sex hormone-binding globulin were determined by radioimmunoassays. Charcoal uptake of 125I cortisol from sera of normal subjects and additional patients with CAH revealed that increased serum cortisol binding by a saturable site, presumably CBG, was associated with CAH. Cortisol binding was significantly correlated with immunoassayable TBG, suggesting that in CAH, similar mechanisms may be responsible for increasing the serum concentrations of CBG and TBG.

  2. Evidence for brain glial activation in chronic pain patients.

    PubMed

    Loggia, Marco L; Chonde, Daniel B; Akeju, Oluwaseun; Arabasz, Grae; Catana, Ciprian; Edwards, Robert R; Hill, Elena; Hsu, Shirley; Izquierdo-Garcia, David; Ji, Ru-Rong; Riley, Misha; Wasan, Ajay D; Zürcher, Nicole R; Albrecht, Daniel S; Vangel, Mark G; Rosen, Bruce R; Napadow, Vitaly; Hooker, Jacob M

    2015-03-01

    Although substantial evidence has established that microglia and astrocytes play a key role in the establishment and maintenance of persistent pain in animal models, the role of glial cells in human pain disorders remains unknown. Here, using the novel technology of integrated positron emission tomography-magnetic resonance imaging and the recently developed radioligand (11)C-PBR28, we show increased brain levels of the translocator protein (TSPO), a marker of glial activation, in patients with chronic low back pain. As the Ala147Thr polymorphism in the TSPO gene affects binding affinity for (11)C-PBR28, nine patient-control pairs were identified from a larger sample of subjects screened and genotyped, and compared in a matched-pairs design, in which each patient was matched to a TSPO polymorphism-, age- and sex-matched control subject (seven Ala/Ala and two Ala/Thr, five males and four females in each group; median age difference: 1 year; age range: 29-63 for patients and 28-65 for controls). Standardized uptake values normalized to whole brain were significantly higher in patients than controls in multiple brain regions, including thalamus and the putative somatosensory representations of the lumbar spine and leg. The thalamic levels of TSPO were negatively correlated with clinical pain and circulating levels of the proinflammatory citokine interleukin-6, suggesting that TSPO expression exerts pain-protective/anti-inflammatory effects in humans, as predicted by animal studies. Given the putative role of activated glia in the establishment and or maintenance of persistent pain, the present findings offer clinical implications that may serve to guide future studies of the pathophysiology and management of a variety of persistent pain conditions.

  3. T wave amplitude in lead aVR as a novel diagnostic marker for cardiac sarcoidosis.

    PubMed

    Tanaka, Yoshihiro; Konno, Tetsuo; Yoshida, Shohei; Tsuda, Toyonobu; Sakata, Kenji; Furusho, Hiroshi; Takamura, Masayuki; Yoshimura, Kenichi; Yamagishi, Masakazu; Hayashi, Kenshi

    2017-03-01

    It is vital to identify cardiac involvement (CI) in patients with sarcoidosis as the condition could initially lead to sudden cardiac death. Although the T wave amplitude in lead aVR (TWAaVR) is reportedly associated with adverse cardiac events in various cardiovascular diseases, only scarce data are available concerning the utility of lead aVR in identifying CI in patients with sarcoidosis. We retrospectively investigated the diagnostic values of TWAaVR in patients with sarcoidosis in comparison with conventional electrocardiography parameters such as bundle branch block (BBB). From January 2006 to December 2014, 93 consecutive patients with sarcoidosis were enrolled (mean age, 55.7 ± 15.7 years; male, 31 %; cardiac involvement, n = 26). TWAaVR showed the greatest sensitivity (39 %) and specificity (92 %) in distinguishing between sarcoidosis patients with and without CI, at a cutoff value of -0.08 mV. The diagnostic value of BBB for cardiac involvement was significantly improved when combined with TWAaVR (sensitivity: 61-94 %, specificity: 97-89 %, area under the curve: 0.79-0.92, p = 0.018). Multivariate logistic regression analysis indicated that TWAaVR and BBB were independent electrocardiography parameters associated with CI. In summary, we observed that sarcoidosis patients exhibiting a high TWAaVR were likely to have CI. Thus, the application of a combination of BBB with TWAaVR may be useful when screening for CI in sarcoidosis patients.

  4. Sarcoidosis in World Trade Center rescue workers presenting with rheumatologic manifestations.

    PubMed

    Bowers, Brian; Hasni, Sarfaraz; Gruber, Barry L

    2010-01-01

    The health consequences of the World Trade Center collapse are unknown, but likely to be significant and may take years to fully appreciate. Sarcoidosis is a multisystem inflammatory disorder of unknown etiology characterized pathologically by noncaseating granulomas. Inciting events, such as infectious agents or possible environmental exposures, have been postulated as the source of antigen exposure initiating an inflammatory cascade. We describe 2 cases of sarcoidosis in rescue workers with significant exposure from the World Trade Center collapse, who presented with extrapulmonary rheumatologic manifestations. Our first case involved a 33-year-old white New York City man detective found to have sarcoidosis following an evaluation of diffuse joint pain. The second case involved a 40-year-old African American man, New York City officer, who presented with uveitis, and was subsequently diagnosed with sarcoidosis. These 2 cases extend the spectrum of disorders resulting from the World Trade Center disaster and illustrate the need for clinicians to be aware of the diverse presentations of sarcoidosis in this patient population.

  5. Resolution of abnormal cardiac MRI T2 signal following immune suppression for cardiac sarcoidosis.

    PubMed

    Crouser, Elliott D; Ruden, Emily; Julian, Mark W; Raman, Subha V

    2016-08-01

    Cardiac MR (CMR) with late gadolinium enhancement is commonly used to detect cardiac damage in the setting of cardiac sarcoidosis. The addition of T2 mapping to CMR was recently shown to enhance cardiac sarcoidosis detection and correlates with increased cardiac arrhythmia risk. This study was conducted to determine if CMR T2 abnormalities and related arrhythmias are reversible following immune suppression therapy. A retrospective study of subjects with cardiac sarcoidosis with abnormal T2 signal on baseline CMR and a follow-up CMR study at least 4 months later was conducted at The Ohio State University from 2011 to 2015. Immune suppression treated participants had a significant reduction in peak myocardial T2 value (70.0±5.5 vs 59.2±6.1 ms, pretreatment vs post-treatment; p=0.017), and 83% of immune suppression treated subjects had objective improvement in cardiac arrhythmias. Two subjects who had received inadequate immune suppression treatment experienced progression of cardiac sarcoidosis. This report indicates that abnormal CMR T2 signal represents an acute inflammatory manifestation of cardiac sarcoidosis that is potentially reversible with adequate immune suppression therapy.

  6. Chronic exposure to alcohol alters network activity and morphology of cultured hippocampal neurons.

    PubMed

    Korkotian, Eduard; Botalova, Alena; Odegova, Tatiana; Segal, Menahem

    2015-03-01

    The effects of chronic exposure to moderate concentrations of ethanol were studied in cultured hippocampal neurons. Network activity, assessed by imaging of [Ca(2+)]i variations, was markedly suppressed following 5 days of exposure to 0.25-1% ethanol. The reduced activity was sustained following extensive washout of ethanol, but the activity recovered by blockade of inhibition with bicuculline. This reduction of network activity was associated with a reduction in rates of mEPSCs, but not in a change in inhibitory synaptic activity. Chronic exposure to ethanol caused a significant reduction in the density of mature dendritic spines, without an effect on dendritic length or arborization. These results indicate that chronic exposure to ethanol causes a reduction in excitatory network drive in hippocampal neurons adding another dimension to the chronic effects of alcohol abuse.

  7. Primary Cardiac Sarcoidosis with Syncope and Refractory Atrial Arrhythmia: A Case Report and Review of the Literature

    PubMed Central

    Thangam, Manoj; Nathan, Sriram; Kar, Biswajit; Petrovic, Marija; Patel, Manish; Loyalka, Pranav; Buja, L. Maximilian

    2016-01-01

    We discuss the case of a 38-year-old black man who presented at our hospital with his first episode of syncope, recently developed atrial arrhythmias refractory to pharmacologic therapy, and a left atrial thrombus. He was diagnosed with primary cardiac sarcoidosis characterized by predominant involvement of the epicardium that caused atrial fibrillation and atrial flutter. Histologic analysis of his epicardial lesions yielded a diagnosis of sarcoidosis. This patient's atrial arrhythmia was successfully treated with a hybrid operation that involved resection of his atrial appendage, an Epicor maze procedure, and radiofrequency ablation during a catheter-based electrophysiologic study. The cardiac sarcoidosis was successfully managed with corticosteroid therapy. Our case report shows that sarcoidosis can initially manifest itself as syncope with new-onset atrial arrhythmia. Sarcoidosis is important in the differential diagnosis because of its progressive nature and its potential for treatment with pharmacologic, surgical, and catheter-based interventions. PMID:27303240

  8. A Case of Sarcoidosis with Interstitial Lung Disease Mimicking Clinically Amyopathic Dermatomyositis and Rapidly Progressive Interstitial Lung Disease

    PubMed Central

    Nogi, Shinichi; Sasaki, Noriko; Chinen, Naofumi; Honda, Kiri; Saito, Eiko; Wakabayashi, Takayuki; Yamada, Chiho; Suzuki, Yasuo

    2014-01-01

    Here, we report a patient with sarcoidosis who developed edematous erythema and interstitial lung disease. At the initial visit, clinically amyopathic dermatomyositis (CADM) with rapidly progressive interstitial lung disease (RP-ILD) was suspected because he had progressive dyspnea but no muscle weakness. The presence of anti-CADM-140/MDA5 autoantibodies was immediately assessed to facilitate a precise diagnosis, with negative results. Thereafter, skin and transbronchial lung biopsies revealed noncaseating granuloma with Langhans giant cells in both specimens, leading to a diagnosis of sarcoidosis. In this case, clinical features of skin and lung were unable to distinguish DM (including CADM) from sarcoidosis, but the lack of anti-CADM-140/MDA5 antibody was useful for differentiating CADM with RP-ILD mimicking sarcoidosis from bona fide sarcoidosis. PMID:25431723

  9. The natural history and long-term outcome of 57 limb sarcoidosis neuropathy cases.

    PubMed

    Burns, T M; Dyck, P J B; Aksamit, A J; Dyck, P J

    2006-05-15

    Fifty-seven patients with biopsy-proven sarcoidosis causing limb neuropathy were reviewed in order to delineate the characteristic symptoms, impairments, disability, course, outcome and response to corticosteroid treatment of limb sarcoid neuropathy. Typically the neuropathy had a definite date of symptomatic onset. Prominent were positive neuropathic sensory symptoms (P-NSS), especially pain, overshadowing weakness and sensory loss. P-NSS were the main cause of disability. Almost always the pattern was asymmetric and not length-dependent (unlike distal polyneuropathy). We inferred (from kind and distribution of symptoms, signs and electrophysiologic and other test results) that the pathologic process was focal or multifocal, involving most classes of nerve fibers and variable levels of proximal to distal levels of roots and peripheral nerves. Additional features aiding in diagnosis were: systemic symptoms such as fatigue, malaise, arthralgia, fever and weight loss; involvement of multiple tissues (i.e. skin, lymph nodes and eye); the patterns of neuropathy; MRI features; and ultimately tissue diagnosis. Axonal degeneration predominated, although an acquired demyelinating process was observed in 3 patients. For most cases, the disease had a chronic, monophasic course. MRI studies done in later years of affected neural structures were helpful in identifying leptomeningeal thickening, hilar adenopathy; and enlargement and T2 enhancement of nerve roots, plexuses, and limb nerves. Corticosteroid treatment appeared to ameliorate symptoms more than impairments. Several variables were associated with neuropathic improvement: CSF pleocytosis, short duration between symptom onset and treatment, and a higher grade of disability at first evaluation-a possible rationale for future earlier diagnosis and treatment.

  10. Extending Admixture Mapping to Nuclear Pedigrees: Application to Sarcoidosis

    PubMed Central

    McKeigue, Paul M.; Colombo, Marco; Agakov, Felix; Datta, Indrani; Levin, Albert; Favro, David; Gray-Montgomery, Courtney; Iannuzzi, Michael C.; Rybicki, Benjamin A.

    2013-01-01

    We describe statistical methods that extend the application of admixture mapping from unrelated individuals to nuclear pedigrees, allowing existing pedigree-based collections to be fully exploited. Computational challenges have been overcome by developing a fast algorithm that exploits the factorial structure of the underlying model of ancestry transitions. This has been implemented as an extension of the program ADMIXMAP. We demonstrate the application of the method to a study of sarcoidosis in African Americans that has previously been analyzed only as an admixture mapping study restricted to unrelated individuals. Although the ancestry signals detected in this pedigree analysis are generally similar to those detected in the earlier analysis of unrelated cases, we are able to extract more information and this yields a much sharper exclusion map; using the classical criterion of an LOD score of minus 2, the pedigree analysis is able to exclude a risk ratio of 2 or more associated with African ancestry over 96% of the genome, compared with only 83% in the earlier analysis of unrelated individuals only. Although the pedigree extension of ADMIXMAP can use ancestry-informative markers only at relatively low density, it can use imputed ancestry states from programs such as WINPOP or HAPMIX that use dense SNP marker genotypes for admixture mapping. This extends both the efficiency and the range of application of this powerful gene mapping method. PMID:23371909

  11. Diffuse Anterior Retinoblastoma with Sarcoidosis-Like Nodule

    PubMed Central

    Kitazawa, Koji; Nagata, Kenji; Yamanaka, Yukito; Kuwahara, Yasumichi; Iehara, Tomoko; Kinoshita, Shigeru; Sotozono, Chie

    2015-01-01

    Background Retinoblastomas account for 4% of malignancies in children, 1-2% of which are diffuse infiltrating retinoblastomas. Diffuse anterior retinoblastoma is rare and does not involve the retina. Here, we report on a diffuse anterior retinoblastoma with large sarcoidosis-like nodules on the iris that were responsive to anti-inflammatory therapy. Case We present a 6-year-old girl who had anterior uveitis with white nodules on the iris and posterior surface of the cornea in her right eye. The nodules initially responded well to anti-inflammatory treatment. However, anterior segment optical coherence tomography (AS-OCT) showed that the nodules gradually grew, shrinking the iris. We then collected the aqueous humor for diagnosis. A biopsy revealed clusters of small cells with a high nuclear-to-cytoplasm ratio with partial rosette formation. Therefore, we diagnosed diffuse anterior retinoblastoma without retinal involvement and performed enucleation of the right eye. The histopathology demonstrated undifferentiated cells similar to those seen on the biopsy, and tumor cells invaded the iris stroma, posterior surface of the cornea, ciliary body, and sclera. After the enucleation, she underwent chemotherapy and remains alive. Conclusion A differential diagnosis of retinoblastoma should be considered when white nodules refractory to anti-inflammatory therapy occur in the eye, even in the absence of obvious retinal masses. AS-OCT findings are useful in assessing retinoblastoma. PMID:26955346

  12. Chronic immune activation and inflammation as the cause of malignancy

    PubMed Central

    O'Byrne, K J; Dalgleish, A G

    2001-01-01

    Several chronic infections known to be associated with malignancy have established oncogenic properties. However the existence of chronic inflammatory conditions that do not have an established infective cause and are associated with the development of tumours strongly suggests that the inflammatory process itself provides the prerequisite environment for the development of malignancy. This environment includes upregulation of mediators of the inflammatory response such as cyclo-oxygenase (COX)-2 leading to the production of inflammatory cytokines and prostaglandins which themselves may suppress cell mediated immune responses and promote angiogenesis. These factors may also impact on cell growth and survival signalling pathways resulting in induction of cell proliferation and inhibition of apoptosis. Furthermore, chronic inflammation may lead to the production of reactive oxygen species and metabolites such as malondialdehyde within the affected cells that may in turn induce DNA damage and mutations and, as a result, be carcinogenic. Here it is proposed that the conditions provided by a chronic inflammatory environment are so essential for the progression of the neoplastic process that therapeutic intervention aimed at inhibiting inflammation, reducing angiogenesis and stimulating cell mediated immune responses may have a major role in reducing the incidence of common cancers. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11506482

  13. Effect of chronic contractile activity on SS and IMF mitochondrial apoptotic susceptibility in skeletal muscle.

    PubMed

    Adhihetty, Peter J; Ljubicic, Vladimir; Hood, David A

    2007-03-01

    Chronic contractile activity of skeletal muscle induces an increase in mitochondria located in proximity to the sarcolemma [subsarcolemmal (SS)] and in mitochondria interspersed between the myofibrils [intermyofibrillar (IMF)]. These are energetically favorable metabolic adaptations, but because mitochondria are also involved in apoptosis, we investigated the effect of chronic contractile activity on mitochondrially mediated apoptotic signaling in muscle. We hypothesized that chronic contractile activity would provide protection against mitochondrially mediated apoptosis despite an elevation in the expression of proapoptotic proteins. To induce mitochondrial biogenesis, we chronically stimulated (10 Hz; 3 h/day) rat muscle for 7 days. Chronic contractile activity did not alter the Bax/Bcl-2 ratio, an index of apoptotic susceptibility, and did not affect manganese superoxide dismutase levels. However, contractile activity increased antiapoptotic 70-kDa heat shock protein and apoptosis repressor with a caspase recruitment domain by 1.3- and 1.4-fold (P<0.05), respectively. Contractile activity elevated SS mitochondrial reactive oxygen species (ROS) production 1.4- and 1.9-fold (P<0.05) during states IV and III respiration, respectively, whereas IMF mitochondrial state IV ROS production was suppressed by 28% (P<0.05) and was unaffected during state III respiration. Following stimulation, exogenous ROS treatment produced less cytochrome c release (25-40%) from SS and IMF mitochondria, and also reduced apoptosis-inducing factor release (approximately 30%) from IMF mitochondria, despite higher inherent cytochrome c and apoptosis-inducing factor expression. Chronic contractile activity did not alter mitochondrial permeability transition pore (mtPTP) components in either subfraction. However, SS mitochondria exhibited a significant increase in the time to Vmax of mtPTP opening. Thus, chronic contractile activity induces predominantly antiapoptotic adaptations in both

  14. Chronic hepatitis C infection–induced liver fibrogenesis is associated with M2 macrophage activation

    PubMed Central

    Bility, Moses T.; Nio, Kouki; Li, Feng; McGivern, David R.; Lemon, Stanley M.; Feeney, Eoin R.; Chung, Raymond T.; Su, Lishan

    2016-01-01

    The immuno-pathogenic mechanisms of chronic hepatitis C virus (HCV) infection remain to be elucidated and pose a major hurdle in treating or preventing chronic HCV-induced advanced liver diseases such as cirrhosis. Macrophages are a major component of the inflammatory milieu in chronic HCV–induced liver disease, and are generally derived from circulating inflammatory monocytes; however very little is known about their role in liver diseases. To investigate the activation and role of macrophages in chronic HCV–induced liver fibrosis, we utilized a recently developed humanized mouse model with autologous human immune and liver cells, human liver and blood samples and cell culture models of monocyte/macrophage and/or hepatic stellate cell activation. We showed that M2 macrophage activation was associated with liver fibrosis during chronic HCV infection in the livers of both humanized mice and patients, and direct-acting antiviral therapy attenuated M2 macrophage activation and associated liver fibrosis. We demonstrated that supernatant from HCV-infected liver cells activated human monocytes/macrophages with M2-like phenotypes. Importantly, HCV-activated monocytes/macrophages promoted hepatic stellate cell activation. These results suggest a critical role for M2 macrophage induction in chronic HCV-associated immune dysregulation and liver fibrosis. PMID:28000758

  15. Chronic hepatitis C infection-induced liver fibrogenesis is associated with M2 macrophage activation.

    PubMed

    Bility, Moses T; Nio, Kouki; Li, Feng; McGivern, David R; Lemon, Stanley M; Feeney, Eoin R; Chung, Raymond T; Su, Lishan

    2016-12-21

    The immuno-pathogenic mechanisms of chronic hepatitis C virus (HCV) infection remain to be elucidated and pose a major hurdle in treating or preventing chronic HCV-induced advanced liver diseases such as cirrhosis. Macrophages are a major component of the inflammatory milieu in chronic HCV-induced liver disease, and are generally derived from circulating inflammatory monocytes; however very little is known about their role in liver diseases. To investigate the activation and role of macrophages in chronic HCV-induced liver fibrosis, we utilized a recently developed humanized mouse model with autologous human immune and liver cells, human liver and blood samples and cell culture models of monocyte/macrophage and/or hepatic stellate cell activation. We showed that M2 macrophage activation was associated with liver fibrosis during chronic HCV infection in the livers of both humanized mice and patients, and direct-acting antiviral therapy attenuated M2 macrophage activation and associated liver fibrosis. We demonstrated that supernatant from HCV-infected liver cells activated human monocytes/macrophages with M2-like phenotypes. Importantly, HCV-activated monocytes/macrophages promoted hepatic stellate cell activation. These results suggest a critical role for M2 macrophage induction in chronic HCV-associated immune dysregulation and liver fibrosis.

  16. Relationship between radiologic patterns, pulmonary function values and bronchoalveolar lavage fluid cells in newly diagnosed sarcoidosis

    PubMed Central

    Zeleckienė, Ingrida; Matačiūnas, Mindaugas; Puronaitė, Roma; Jurgauskienė, Laimutė; Malickaitė, Radvilė; Strumilienė, Edita; Gruslys, Vygantas; Zablockis, Rolandas; Danila, Edvardas

    2017-01-01

    Background The aim of the present study was to identify specious radiologic and/or physiologic prognostic marker(s), which lead to optimize of the patient follow-up frequency. Methods Eighty consecutive patients with newly diagnosed pulmonary sarcoidosis. Patients underwent chest radiography, high-resolution computed tomography (HRCT) examination, pulmonary function tests (PFT), bronchoscopy with bronchoalveolar lavage (BAL) and lung biopsy, and bronchoalveolar lavage fluid (BALF) cell examination. Results The reduction in PFT values seen in radiological sarcoidosis stage III was greater than that seen in stages I and II. The percentage of neutrophils in the lungs was found to increase in stages II and III. PFT indices were correlated negatively with the consolidation and ground glass opacities CT scores, but not with the micronodule or macronodule scores. The rise in the percentage of BALF lymphocytes was associated with the restriction pattern of PFT. The diagnostic value of BALF for sarcoidosis was higher when the typical radiologic patterns of stage I disease were found and that smoking decreased the diagnostic value of CD4/CD8 ratio. Conclusions This study supports the opinion that the staging of the pulmonary sarcoidosis with chest X-rays is still valuable from the prognostic point of view, because significant correlations between the radiologic stages of sarcoidosis and PFT parameters were found. Chest HRCT was significantly superior to chest X-ray in detecting mediastinal and pulmonary parenchymal changes. However, the prognostic role of HRCT needs to be better investigated evaluating serial examinations. Only consolidation and ground glass scores (neither of which are frequently found in sarcoidosis) hold prognostic value, since these were negatively correlated with PFT parameters. PMID:28203410

  17. Polygenic risk assessment reveals pleiotropy between sarcoidosis and inflammatory disorders in the context of genetic ancestry.

    PubMed

    Lareau, C A; DeWeese, C F; Adrianto, I; Lessard, C J; Gaffney, P M; Iannuzzi, M C; Rybicki, B A; Levin, A M; Montgomery, C G

    2017-03-09

    Sarcoidosis is a complex disease of unknown etiology characterized by the presence of granulomatous inflammation. Though various immune system pathways have been implicated in disease, the relationship between the genetic determinants of sarcoidosis and other inflammatory disorders has not been characterized. Herein, we examined the degree of genetic pleiotropy common to sarcoidosis and other inflammatory disorders to identify shared pathways and disease systems pertinent to sarcoidosis onset. To achieve this, we quantify the association of common variant polygenic risk scores from nine complex inflammatory disorders with sarcoidosis risk. Enrichment analyses of genes implicated in pleiotropic associations were further used to elucidate candidate pathways. In European-Americans, we identify significant pleiotropy between risk of sarcoidosis and risk of asthma (R(2)=2.03%; P=8.89 × 10(-9)), celiac disease (R(2)=2.03%; P=8.21 × 10(-9)), primary biliary cirrhosis (R(2)=2.43%; P=2.01 × 10(-10)) and rheumatoid arthritis (R(2)=4.32%; P=2.50 × 10(-17)). These associations validate in African Americans only after accounting for the proportion of genome-wide European ancestry, where we demonstrate similar effects of polygenic risk for African-Americans with the highest levels of European ancestry. Variants and genes implicated in European-American pleiotropic associations were enriched for pathways involving interleukin-12, interleukin-27 and cell adhesion molecules, corroborating the hypothesized immunopathogenesis of disease.Genes and Immunity advance online publication, 9 March 2017; doi:10.1038/gene.2017.3.

  18. Chronic beryllium disease: Diagnosis and management

    SciTech Connect

    Rossman, M.D.

    1996-10-01

    Chronic beryllium disease is predominantly a pulmonary granulomatosis that was originally described in 1946. Symptoms usually include dyspnea and cough. Fever, anorexia, and weight loss are common. Skin lesions are the most common extrathoracic manifestation. Granulomatous hepatitis, hypercalcemia, and kidney stones can also occur. Radiographic and physiologic abnormalities are similar to those in sarcoidosis. While traditionally the pathologic changes included granulomas and cellular interstitial changes, the hallmark of the disease today is the well-formed granuloma. Immunologic studies have demonstrated a cell-mediated response to beryllium that is due to an accumulation of CD4{sup +} T cells at the site of disease activity. Diagnosis depends on the demonstration of pathologic changes (i.e., granuloma) and evidence that the granuloma was caused by a hypersensitivity to beryllium (i.e., positive lung proliferative response to beryllium). Using these criteria, the diagnosis of chronic beryllium disease can now be made before the onset of clinical symptoms. Whether, with early diagnosis, the natural course of this condition will be the same as when it was traditionally diagnosed is not known. Currently, corticosteroids are used to treat patients with significant symptoms or evidence of progressive disease. 21 refs.

  19. Sarcoidosis imitating breast cancer metastasis: a case report and literature review

    PubMed Central

    Kochoyan, Teimuraz; Akhmedov, Mobil; Shabanov, Alexander; Terekhov, Ilya

    2016-01-01

    Sarcoidosis is a benign systematic granulomatous disorder of unknown etiology and is associated with various malignancies. However, granulomatous and metastatic lymph node lesions are difficult to distinguish even when using precise and modern diagnostic methods, such as positron emission tomography. Thus, histological verification is the only method that can be used to accurately describe the nature of this disease. In this article, we report a case of non-luminal HER-2/neu-positive breast cancer in a patient without history of sarcoidosis and suspected to have metastatic disease. PMID:27807507

  20. Sarcoidosis of the cauda equina mimicking Guillain-Barré syndrome.

    PubMed

    Shah, Jagdish R; Lewis, Richard A

    2003-04-15

    Neurosarcoidosis is a great mimicker. It is often difficult to diagnose particularly when there is no prior history of systemic sarcoidosis. Although certain sites of the neuraxis are more commonly involved than others, any site of the central or peripheral nervous system can be affected. We report a case of sarcoidosis involving the cauda equina in a 38-year-old African American male without prior history of systemic disease. Initial clinical presentation was suggestive of Guillian-Barré syndrome, but the evaluation proved this case to be neurosarcoidosis involving the cauda equina. We have followed this patient for 8 years, and he remains clinically stable on prednisone 5 mg/day.

  1. Immunomodulatory activity of interleukin-27 in human chronic periapical diseases

    PubMed Central

    Li, Juan; Wang, Rong; Huang, Shi-Guang

    2017-01-01

    This study aims to observe expression of IL-27 on different cells in periapical tissues of different types of human chronic periapical diseases. Periapical tissue specimens of 60 donors, including healthy control (n=20), periapical granuloma group (n=20) and radicular cysts group (n=20), were fixed in 10% buffered formalin, stained with hematoxylin and eosin for histopathology. Then specimens were stained with double- immuno-fluorescence assay for identification of IL-27-tryptase (mast cells, MCs), IL-27-CD14 (mononuclear phagocyte cells, MPs) and IL-27-CD31 (endothelial cells, ECs) double-positive cells in periapical tissues. The results indicated that compared with healthy control, the densities (cells/mm2) of IL-27-tryptase, IL-27-CD14 and IL-27-CD31 double-positive cells were significantly increased in human chronic periapical diseases (periapical granuloma group and radicular cysts group) (P<0.001). The density of IL-27-tryptase double positive cells in radicular cysts group was significantly higher than those in periapical granuloma group (P<0.001). Densities of IL-27-CD14 and IL-27-CD31 double-positive cells in periapical granuloma group had no significant difference with those in radicular cysts group (P=0.170 and 0.138, respectively). IL-27-CD14 double positive cells density achieved to peak among three cell groups in radicular cysts groups. In conclusion, IL-27 expressed in MCs, MPs and ECs of human chronic periapical diseases with different degrees. IL-27-tryptase double-positive cells may participate in pathogenic mechanism of chronic periapical diseases, especially for formation of fibrous in periapical cysts. IL-27-CD14 and IL-27-CD31 double-positive cells may participate in immunologic response to resist periapical infection, and they may play an dual role in pathogenesis and localization of periapical diseases. PMID:28386371

  2. Pathophysiology of Pulmonary Hypertension in Chronic Parenchymal Lung Disease.

    PubMed

    Singh, Inderjit; Ma, Kevin Cong; Berlin, David Adam

    2016-04-01

    Pulmonary hypertension commonly complicates chronic obstructive pulmonary disease and interstitial lung disease. The association of chronic lung disease and pulmonary hypertension portends a worse prognosis. The pathophysiology of pulmonary hypertension differs in the presence or absence of lung disease. We describe the physiological determinants of the normal pulmonary circulation to better understand the pathophysiological factors implicated in chronic parenchymal lung disease-associated pulmonary hypertension. This review will focus on the pathophysiology of 3 forms of chronic lung disease-associated pulmonary hypertension: idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, and sarcoidosis.

  3. Increased peroxisome proliferator-activated receptor-gamma activity reduces imatinib uptake and efficacy in chronic myeloid leukemia mononuclear cells.

    PubMed

    Wang, Jueqiong; Lu, Liu; Kok, Chung H; Saunders, Verity A; Goyne, Jarrad M; Dang, Phuong; Leclercq, Tamara M; Hughes, Timothy P; White, Deborah L

    2017-02-02

    Imatinib is actively transported by OCT-1 influx transporter, and low OCT-1 activity in diagnostic chronic myeloid leukemia blood mononuclear cells is significantly associated with poor molecular response to imatinib. Here we report that, in diagnostic chronic myeloid leukemia mononuclear cells and BCR-ABL1+ cell lines, peroxisome proliferator-activated receptor gamma agonists (GW1929, rosiglitazone, pioglitazone) significantly decrease OCT-1 activity; conversely, peroxisome proliferator-activated receptor gamma antagonists (GW9662, T0070907) increase OCT-1 activity. Importantly, these effects can lead to corresponding changes in sensitivity to Bcr-Abl kinase inhibition. Results were confirmed in peroxisome proliferator-activated receptor gamma-transduced K562 cells. Furthermore, we identified a strong negative correlation between OCT-1 activity and peroxisome proliferator-activated receptor gamma transcriptional activity in diagnostic chronic myeloid leukemia patients (n=84; p<0.0001), suggesting that peroxisome proliferator-activated receptor gamma activation has a negative impact on the intracellular uptake of imatinib and consequent Bcr-Abl kinase inhibition. The inter-patient variability of peroxisome proliferator-activated receptor gamma activation likely accounts for the heterogeneity observed in patient OCT-1 activity at diagnosis. Recently, the peroxisome proliferator-activated receptor gamma agonist pioglitazone was reported to act synergistically with imatinib targeting the residual chronic myeloid leukemia stem cell pool. Our findings suggest that peroxisome proliferator-activated receptor gamma ligands have differential effects on circulating mononuclear cells compared to stem cells. Since the effect of peroxisome proliferator-activated receptor gamma activation on imatinib uptake in mononuclear cells may counteract the clinical benefit of this activation in stem cells, caution should be applied when combining these therapies, especially in patients

  4. Obesity in children and adolescents with chronic pain: Associations with pain and activity limitations

    PubMed Central

    Wilson, Anna C.; Samuelson, Bethany; Palermo, Tonya M.

    2010-01-01

    Objectives Obesity is associated with functional disability in adults with chronic pain, but less is known about obesity among youth with chronic pain. The purpose of this study was to 1) identify the prevalence of overweight and obesity in children and adolescents receiving treatment for chronic pain, and 2) examine associations between Body Mass Index (BMI), pain intensity, and activity limitations in this population. Methods Data was obtained from records of 118 patients, ages 8 to 18, seen in a multidisciplinary pediatric pain clinic. Information about age, gender, pain problem, duration and severity, medical diagnoses, medications, height and weight were collected from medical records and intake questionnaires. The CDC’s pediatric BMI calculator was used to obtain percentile and category (underweight, healthy weight, overweight, obese). Children and parents completed the Child Activity Limitations Interview-21 (CALI-21), a self-report measure of activity limitations. Results A significantly higher rate of overweight and obesity was observed among youth with chronic pain compared to a normative sample. BMI percentile was predictive of concurrent limitations in vigorous activities, according to parent report. Discussion BMI percentile and weight status may contribute to activity limitations among children and adolescents with chronic pain. Weight status is an important factor to consider in the context of treatment of chronic pain and disability in children and adolescents. PMID:20664337

  5. Differential Neural Processing during Motor Imagery of Daily Activities in Chronic Low Back Pain Patients

    PubMed Central

    Vrana, Andrea; Hotz-Boendermaker, Sabina; Stämpfli, Philipp; Hänggi, Jürgen; Seifritz, Erich; Humphreys, B. Kim; Meier, Michael L.

    2015-01-01

    Chronic low back pain (chronic LBP) is both debilitating for patients but also a major burden on the health care system. Previous studies reported various maladaptive structural and functional changes among chronic LBP patients on spine- and supraspinal levels including behavioral alterations. However, evidence for cortical reorganization in the sensorimotor system of chronic LBP patients is scarce. Motor Imagery (MI) is suitable for investigating the cortical sensorimotor network as it serves as a proxy for motor execution. Our aim was to investigate differential MI-driven cortical processing in chronic LBP compared to healthy controls (HC) by means of functional magnetic resonance imaging (fMRI). Twenty-nine subjects (15 chronic LBP patients, 14 HC) were included in the current study. MI stimuli consisted of randomly presented video clips showing every-day activities involving different whole-body movements as well as walking on even ground and walking downstairs and upstairs. Guided by the video clips, subjects had to perform MI of these activities, subsequently rating the vividness of their MI performance. Brain activity analysis revealed that chronic LBP patients exhibited significantly reduced activity compared to HC subjects in MI-related brain regions, namely the left supplementary motor area and right superior temporal sulcus. Furthermore, psycho-physiological-interaction analysis yielded significantly enhanced functional connectivity (FC) between various MI-associated brain regions in chronic LBP patients indicating diffuse and non-specific changes in FC. Current results demonstrate initial findings about differences in MI-driven cortical processing in chronic LBP pointing towards reorganization processes in the sensorimotor network. PMID:26569602

  6. Chronic Fatigue Syndrome (CFS): Managing Activities and Exercise

    MedlinePlus

    ... Fatigue Syndrome (CFS) Share Compartir Managing Activities and Exercise On this Page Avoiding Extremes Developing an Activity ... recent manageable level of activity. Strength and Conditioning Exercises Strength and conditioning exercises are an important component ...

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

    PubMed Central

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

    2015-01-01

    In recent years, it has become clear that chronic systemic low-grade inflammation is at the root of many, if not all, typically Western diseases associated with the metabolic syndrome. While much focus has been given to sedentary lifestyle as a cause of chronic inflammation, it is less often appreciated that chronic inflammation may also promote a sedentary lifestyle, which in turn causes chronic inflammation. Given that even minor increases in chronic inflammation reduce brain volume in otherwise healthy individuals, the bidirectional relationship between inflammation and sedentary behaviour may explain why humans have lost brain volume in the last 30,000 years and also intelligence in the last 30 years. We review evidence that lack of physical activity induces chronic low-grade inflammation and, consequently, an energy conflict between the selfish immune system and the selfish brain. Although the notion that increased physical activity would improve health in the modern world is widespread, here we provide a novel perspective on this truism by providing evidence that recovery of normal human behaviour, such as spontaneous physical activity, would calm proinflammatory activity, thereby allocating more energy to the brain and other organs, and by doing so would improve human health. PMID:26074674

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

    PubMed

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

    2015-01-01

    In recent years, it has become clear that chronic systemic low-grade inflammation is at the root of many, if not all, typically Western diseases associated with the metabolic syndrome. While much focus has been given to sedentary lifestyle as a cause of chronic inflammation, it is less often appreciated that chronic inflammation may also promote a sedentary lifestyle, which in turn causes chronic inflammation. Given that even minor increases in chronic inflammation reduce brain volume in otherwise healthy individuals, the bidirectional relationship between inflammation and sedentary behaviour may explain why humans have lost brain volume in the last 30,000 years and also intelligence in the last 30 years. We review evidence that lack of physical activity induces chronic low-grade inflammation and, consequently, an energy conflict between the selfish immune system and the selfish brain. Although the notion that increased physical activity would improve health in the modern world is widespread, here we provide a novel perspective on this truism by providing evidence that recovery of normal human behaviour, such as spontaneous physical activity, would calm proinflammatory activity, thereby allocating more energy to the brain and other organs, and by doing so would improve human health.

  9. Disordered Toll-like receptor 2 responses in the pathogenesis of pulmonary sarcoidosis.

    PubMed

    Gabrilovich, M I; Walrath, J; van Lunteren, J; Nethery, D; Seifu, M; Kern, J A; Harding, C V; Tuscano, L; Lee, H; Williams, S D; Mackay, W; Tomashefski, J F; Silver, R F

    2013-09-01

    In this study, we hypothesized that the granulomatous disorder sarcoidosis is not caused by a single pathogen, but rather results from abnormal responses of Toll-like receptors (TLRs) to conserved bacterial elements. Unsorted bronchoalveolar lavage (BAL) cells from patients with suspected pulmonary sarcoidosis and healthy non-smoking control subjects were stimulated with representative ligands of TLR-2 (in both TLR-2/1 and TLR-2/6 heterodimers) and TLR-4. Responses were determined by assessing resulting production of tumour necrosis factor (TNF)-α and interleukin (IL)-6. BAL cells from patients in whom sarcoidosis was confirmed displayed increased cytokine responses to the TLR-2/1 ligand 19-kDa lipoprotein of Mycobacterium tuberculosis (LpqH) and decreased responses to the TLR-2/6 agonist fibroblast stimulating ligand-1 (FSL)-1. Subsequently, we evaluated the impact of TLR-2 gene deletion in a recently described murine model of T helper type 1 (Th1)-associated lung disease induced by heat-killed Propionibacterium acnes. As quantified by blinded scoring of lung pathology, P. acnes-induced granulomatous pulmonary inflammation was markedly attenuated in TLR-2(-/-) mice compared to wild-type C57BL/6 animals. The findings support a potential role for disordered TLR-2 responses in the pathogenesis of pulmonary sarcoidosis.

  10. Ga-67 positivity in sarcoidosis of the skin with coincident thyroid uptake of uncertain etiology

    SciTech Connect

    Moreno, A.J.; Brown, J.M.; Salinas, J.A.; Feaster, B.L.; Brown, T.J.

    1984-03-01

    Gallium-67 citrate scintigraphy of a 26-year-old woman with systemic sarcoidosis demonstrated abnormal radiotracer uptake within multiple biopsy-proven sarcoidal cutaneous lesions and within both lobes of the thyroid gland. The etiology of the thyroidal uptake of the Ga-67 was uncertain but it may represent sarcoidal involvement of the gland.

  11. Efficacy of additional treatment with azathioprine in a patient with prednisolone-dependent gastric sarcoidosis

    PubMed Central

    Murata, Masaki; Sugimoto, Mitsushige; Yokota, Yoshihiro; Ban, Hiromitsu; Inatomi, Osamu; Bamba, Shigeki; Kushima, Ryoji; Andoh, Akira

    2016-01-01

    Gastric sarcoidosis with noncaseating granuloma is rare. Although corticosteroid produces a dramatic clinical response, it is unknown whether azathioprine show efficacy in prednisolone-dependent cases. Here, we report a case of gastric sarcoidosis in a 25-year-old man with severe epigastlargia. Gastroendoscopy revealed multiple map-like ulcerations. Histological examination showed multiple noncaseating granulomatous lesions in gastric mucosa, which were incompatible with diagnoses of Crohn’s disease or tuberculosis. He was started on prednisolone at 30 mg/d, and his symptoms improved within 7-d. The prednisolone was gradually tapered by 5 mg every 2-wk, but oral azathioprine at 50 mg was added after symptoms recurred at tapered dose of 10 mg. Endoscopy 4-wk later showed healing ulcers, and, lymphocytic infiltration was absent. The efficacy of additional azathioprine in gastric sarcoidosis is not well defined. Here, we report a case of prednisolone-dependent gastric sarcoidosis that improved after additional azathioprine, and also review the literature concerning the treatment, especially for prednisolone-dependent cases. PMID:28058029

  12. Prevalence of cardiac sarcoidosis in white population: a case–control study

    PubMed Central

    Martusewicz-Boros, Magdalena M.; Boros, Piotr W.; Wiatr, Elżbieta; Zych, Jacek; Piotrowska-Kownacka, Dorota; Roszkowski-Śliż, Kazimierz

    2016-01-01

    Abstract Cardiac sarcoidosis (CS) is a life-threatening and underdiagnosed manifestation of the disease, which requires a complicated and expensive diagnostic pathway. There is a need for simple tool for practitioners to determine the risk of CS without access to specialized equipment. The aim of study was to determine the prevalence of CS in a group of patients diagnosed with or followed up because of sarcoidosis. A secondary objective was the search for factors associated with heart involvement. We performed a prospective case–control study (screening analysis) in consecutive sarcoidosis patients collected from October 2012 to September 2015. Cardiac magnetic resonance (CMR) imaging was performed to confirm or exclude cardiac involvement in all patients. The study was conducted in a hospital-based referral center for patients with sarcoidosis and other interstitial lung diseases. Analysis was performed in a group of 201 patients (all white) with biopsy-proven sarcoidosis, mean age 41.4 ± 10.2, 121 of them (60.2%) males. Four patients with previously recognized cardiac diseases, which make CMR imaging for CS inconclusive, were not included. Cardiac involvement was detected by CMR in 49 patients (24.4%). Factors associated with an increased risk of CS (univariate analyses) included male sex (odds ratio [OR]: 2.5; 1.21–5.16, P = 0.01), cardiac-related symptoms (OR: 3.53; 1.81–6.89, P = 0.0002), extrathoracic sarcoidosis (OR: 3.48; 1.77–6.84, P = 0.0003), elevated serum NT-proBNP (OR: 3.82; 1.55–9.42, P = 0.004), any electrocardiography abnormality (OR: 5.38; 2.48–11.67, P = 0.0001), and contemporary radiological progression sarcoidosis in the lungs (OR: 2.98; 1.52–5.84, P = 0.001). Abnormalities in echocardiography and Holter ECG were also risk factors, but not significant in multivariate analyses. A CS Risk Index was developed using a multivariate model to predict CS, achieving an accuracy of 82%, sensitivity of 50

  13. In-Hospital Disease Burden of Sarcoidosis in Switzerland from 2002 to 2012.

    PubMed

    Pohle, Susanne; Baty, Florent; Brutsche, Martin

    2016-01-01

    Sarcoidosis is a multisystem disease with an unpredictable and sometimes fatal course while the underlying pathomechanism is still unclear. Reasons of the increasing hospitalization rate and mortality in the United States remain in dispute but incriminated are a number of distinct comorbidities and risk factors as well as the application of more aggressive therapeutic agents. Studies reflecting the recent development in central Europe are lacking. Our aim was to investigate the recent mortality and hospitalization rates as well as the underlying comorbidities of hospitalized sarcoidosis patients in Switzerland. In this longitudinal, nested case-control study, a nation-wide database provided by the Swiss Federal Office for Statistics enclosing every hospital entry covering the years 2002-2012 (n = 15,627,573) was analyzed. There were 8,385 cases with a diagnosis of sarcoidosis representing 0.054% (8,385 / 15,627,573) of all hospitalizations in Switzerland. These cases were compared with age- and sex-matched controls without the diagnosis of sarcoidosis. Hospitalization and mortality rates in Switzerland remained stable over the observed time period. Comorbidity analysis revealed that sarcoidosis patients had significantly higher medication-related comorbidities compared to matched controls, probably due to systemic corticosteroids and immunosuppressive therapy. Sarcoidosis patients were also more frequently re-hospitalized (median annual hospitalization rate 0.28 [IQR 0.15-0.65] vs. 0.19 [IQR 0.13-0.36] per year; p < 0.001), had a longer hospital stay (6 [IQR 2-13] vs. 4 [IQR 1-8] days; p < 0.001), had more comorbidities (4 [IQR 2-7] vs. 2 [IQR 1-5]; p < 0.001), and had a significantly higher in-hospital mortality (2.6% [95% CI 2.3%-2.9%] vs. 1.8% [95% CI 1.5%-2.1%] (p < 0.001). A worse outcome was observed among sarcoidosis patients having co-occurrence of associated respiratory diseases. Moreover, age was an important risk factor for re-hospitalization.

  14. [Effects of chronic Semax administration on exploratory activity and emotional reaction in white rats].

    PubMed

    Vilenskiĭ, D A; Levitskaia, N G; Andreeva, L A; Alfeeva, L Iu; Kamenskiĭ, A A; Miasoedov, N F

    2007-06-01

    Effects of chronic intranasal administration of ACTH(4-10) analog Semax (MEHFPGP) on exploratory activity, anxiety level, and depression-like behaviour were studied in white rats. The peptide was injected daily in dose 0.05 mg/kg during 10 or 14 days. It was shown that chronic Semax administration at 1-2 weeks induced anxiolytic and antidepressant effects but did not influenced the exploratory activity in non-stressogenic environment. The Semax effects may be the results of activation of the brain serotoninergic system as well as increased BDNF expression in the rat hippocampus.

  15. Real-World Affected Upper Limb Activity in Chronic Stroke: An Examination of Potential Modifying Factors

    PubMed Central

    Bailey, Ryan R.; Birkenmeier, Rebecca L.; Lang, Catherine E.

    2015-01-01

    BACKGROUND Despite improvement in motor function after intervention, adults with chronic stroke experience disability in everyday activity. Factors other than motor function may influence affected upper limb (UL) activity. OBJECTIVE To characterize affected UL activity and examine potential modifying factors of affected UL activity in community-dwelling adults with chronic stroke. METHODS Forty-six adults with chronic stroke wore accelerometers on both ULs for 25 hours and provided information about potential modifying factors (time spent in sedentary activity, cognitive impairment, depressive symptomatology, number of comorbidities, motor dysfunction of the affected UL, age, activities of daily living (ADL) status, and living arrangement). Accelerometry was used to quantify duration of affected and unaffected UL activity. The ratio of affected-to-unaffected UL activity was also calculated. Associations within and between accelerometry-derived variables and potential modifying factors were examined. RESULTS Mean hours of affected and unaffected UL activity were 5.0 ± 2.2 and 7.6 ± 2.1 hours, respectively. The ratio of affected-to-unaffected UL activity was 0.64 ± 0.19, and hours of affected and unaffected UL activity were strongly correlated (r=0.78). Increased severity of motor dysfunction and dependence in ADLs were associated with decreased affected UL activity. No other factors were associated with affected UL activity. CONCLUSIONS Severity of motor dysfunction and ADL status should be taken into consideration when setting goals for UL activity in people with chronic stroke. Given the strong, positive correlation between affected and unaffected UL activity, encouragement to increase activity of the unaffected UL may increase affected UL activity. PMID:25776118

  16. Chronic Alcohol Ingestion Delays T Cell Activation and Effector Function in Sepsis

    PubMed Central

    Margoles, Lindsay M.; Mittal, Rohit; Klingensmith, Nathan J.; Lyons, John D.; Liang, Zhe; Serbanescu, Mara A.; Wagener, Maylene E.

    2016-01-01

    Sepsis is the leading cause of death in intensive care units in the US, and it is known that chronic alcohol use is associated with higher incidence of sepsis, longer ICU stays, and higher mortality from sepsis. Both sepsis and chronic alcohol use are associated with immune deficits such as decreased lymphocyte numbers, impaired innate immunity, delayed-type hypersensitivity reactions, and susceptibility to infections; however, understanding of specific pathways of interaction or synergy between these two states of immune dysregulation is lacking. This study therefore sought to elucidate mechanisms underlying the immune dysregulation observed during sepsis in the setting of chronic alcohol exposure. Using a murine model of chronic ethanol ingestion followed by sepsis induction via cecal ligation and puncture, we determined that while CD4+ and CD8+ T cells isolated from alcohol fed mice eventually expressed the same cellular activation markers (CD44, CD69, and CD43) and effector molecules (IFN-γ, TNF) as their water fed counterparts, there was an overall delay in the acquisition of these phenotypes. This early lag in T cell activation was associated with significantly reduced IL-2 production at a later timepoint in both the CD4+ and CD8+ T cell compartments in alcohol sepsis, as well as with a reduced accumulation of CD8dim activated effectors. Taken together, these data suggest that delayed T cell activation may result in qualitative differences in the immune response to sepsis in the setting of chronic alcohol ingestion. PMID:27861506

  17. Targeting type I interferon-mediated activation restores immune function in chronic HIV infection.

    PubMed

    Zhen, Anjie; Rezek, Valerie; Youn, Cindy; Lam, Brianna; Chang, Nelson; Rick, Jonathan; Carrillo, Mayra; Martin, Heather; Kasparian, Saro; Syed, Philip; Rice, Nicholas; Brooks, David G; Kitchen, Scott G

    2017-01-03

    Chronic immune activation, immunosuppression, and T cell exhaustion are hallmarks of HIV infection, yet the mechanisms driving these processes are unclear. Chronic activation can be a driving force in immune exhaustion, and type I interferons (IFN-I) are emerging as critical components underlying ongoing activation in HIV infection. Here, we have tested the effect of blocking IFN-I signaling on T cell responses and virus replication in a murine model of chronic HIV infection. Using HIV-infected humanized mice, we demonstrated that in vivo blockade of IFN-I signaling during chronic HIV infection diminished HIV-driven immune activation, decreased T cell exhaustion marker expression, restored HIV-specific CD8 T cell function, and led to decreased viral replication. Antiretroviral therapy (ART) in combination with IFN-I blockade accelerated viral suppression, further decreased viral loads, and reduced the persistently infected HIV reservoir compared with ART treatment alone. Our data suggest that blocking IFN-I signaling in conjunction with ART treatment can restore immune function and may reduce viral reservoirs during chronic HIV infection, providing validation for IFN-I blockade as a potential therapy for HIV infection.

  18. Microglia activation regulates GluR1 phosphorylation in chronic unpredictable stress-induced cognitive dysfunction.

    PubMed

    Liu, Mingchao; Li, Juan; Dai, Peng; Zhao, Fang; Zheng, Gang; Jing, Jinfei; Wang, Jiye; Luo, Wenjing; Chen, Jingyuan

    2015-01-01

    Chronic stress is considered to be a major risk factor in the development of psychopathological syndromes in humans. Cognitive impairments and long-term potentiation (LTP) impairments are increasingly recognized as major components of depression, anxiety disorders and other stress-related chronic psychological illnesses. It seems timely to systematically study the potentially underlying neurobiological mechanisms of altered cognitive and synaptic plasticity in the course of chronic stress. In the present study, a rat model of chronic unpredictable stress (CUS) induced a cognitive impairment in spatial memory in the Morris water maze (MWM) test and a hippocampal LTP impairment. CUS also induced hippocampal microglial activation and attenuated phosphorylation of glutamate receptor 1 (GluR1 or GluA1). Moreover, chronic treatment with the selective microglial activation blocker, minocycline (120 mg/kg per day), beginning 3 d before CUS treatment and continuing through the behavioral testing period, prevented the CUS-induced impairments of spatial memory and LTP induction. Additional studies showed that minocycline-induced inhibition of microglia activation was associated with increased phosphorylation of GluR1. These results suggest that hippocampal microglial activation modulates the level of GluR1 phosphorylation and might play a causal role in CUS-induced cognitive and LTP disturbances.

  19. [Autonomy of the patient with chronic diseases: from passive patient to active patient].

    PubMed

    González Mestre, Assumpció

    2014-01-01

    Due to social, economic and cultural changes, there has been a transformation of Health Services around the world. A new figure has emerged from this: the Active Patient, more responsible, with more information and willing to change his life as a chronic patient. In order to respond to this new situation, several countries have established initiatives such as self-reliance programmes for chronic patients. The aim of this article is to underline the Expert Patient Programme Catalonia(®) and to explain its operation and the results obtained up until now. The purpose of this program is to improve the experience of chronic disease by patients, from meetings in which an expert patient provides his knowledge and experiences to a group of patients with the same disease, with the aim of promoting changes in habits and lifestyles that improve the quality of life and the coexistence of the person with his chronic process.

  20. Serum soluble interleukin-2 receptor level is more sensitive than angiotensin-converting enzyme or lysozyme for diagnosis of sarcoidosis and may be a marker of multiple organ involvement.

    PubMed

    Thi Hong Nguyen, Chuyen; Kambe, Naotomo; Kishimoto, Izumi; Ueda-Hayakawa, Ikuko; Okamoto, Hiroyuki

    2017-03-11

    Skin lesions in sarcoidosis are often the initial symptoms that enable the dermatologist to be the first to diagnose this granulomatosis. However, diagnosis is sometimes very problematic. In 2015, the diagnostic criteria for sarcoidosis were updated in Japan, with elevated serum soluble interleukin-2 receptor (sIL-2R) replacing negative tuberculin reaction. Therefore, we assessed the clinical utility of sIL-2R compared with two other common markers, angiotensin-converting enzyme (ACE) and lysozyme, in patients who visited the dermatology clinic. Data from 72 patients showed that sIL-2R was more sensitive than both ACE and lysozyme in supporting a diagnosis of sarcoidosis (52.8%) compared with ACE (29%) and lysozyme (26.4%). Additionally, the sIL-2R level was significantly higher in patients with multiple organ involvement and parenchymal infiltration. Patients with elevated sIL-2R levels had higher serum ACE and lysozyme levels, a higher incidence of pulmonary involvement, more severe chest radiographic stage and a high incidence of expression-specific signs by imaging analysis. Receiver-operator curve analysis showed that sIL-2R was a better marker at the threshold cut-off point compared with ACE and lysozyme for identifying patients with multiple organ involvement, detecting patients with pulmonary disease and parenchymal infiltration as well as predicting the presence of specific signs in the diagnosis of sarcoidosis. Moreover, the kinetics of sIL-2R levels correlated closely with clinical manifestations, in contrast to the modest changes of ACE and lysozyme levels during the follow-up period. In conclusion, sIL-2R may be considered a good marker for diagnosis and a potential indicator of disease activity.

  1. [Combination of two signals of danger--a principal cause of activation of chronic inflammatory processes].

    PubMed

    Lebedev, K A

    2012-01-01

    Chronic inflammatory processes have long current during which there is a change of remission by an aggravation of disease. Until recently was considered, that occurrence and activation of chronic inflammatory process is caused by one signal of danger. Most often it are served with microorganisms. The sum of our end literary data shows that activation is connected with accumulation in the center of an inflammation of macrophages and their hyperactivation as a result of action of two signals of danger--microorganisms and xenobiotics.

  2. Aberrant activation of ROS1 represents a new molecular defect in chronic myelomonocytic leukemia.

    PubMed

    Cilloni, Daniela; Carturan, Sonia; Bracco, Enrico; Campia, Valentina; Rosso, Valentina; Torti, Davide; Calabrese, Chiara; Gaidano, Valentina; Niparuck, Pimjai; Favole, Alessandra; Signorino, Elisabetta; Iacobucci, Ilaria; Morano, Annalisa; De Luca, Luciana; Musto, Pellegrino; Frassoni, Francesco; Saglio, Giuseppe

    2013-05-01

    Chronic myelomonocytic leukemia (CMML) is a clonal disorder sharing features of myelodysplastic syndromes and chronic myeloproliferative neoplasms. Although rare chromosomal aberrations and point mutations are reported in CMML, the molecular defects underlying CMML are largely unknown. ROS1 encodes a tyrosine kinase that is abnormally expressed and translocated in brain and lung cancers. In this study we show that ROS1 is abnormally activated in the CD34+ compartment of approximately 70% of CMML patients resulting in the activation of the Erk/Akt pathways through the Grb2/SOS complex thus revealing a central oncogenic role for ROS1 in CMML which might represent a molecular target.

  3. Chronic multiscale imaging of neuronal activity in the awake common marmoset

    PubMed Central

    Yamada, Yoshiyuki; Matsumoto, Yoshifumi; Okahara, Norio; Mikoshiba, Katsuhiko

    2016-01-01

    We report a methodology to chronically record in vivo brain activity in the awake common marmoset. Over a month, stable imaging revealed macroscopic sensory maps in the somatosensory cortex and their underlying cellular activity with a high signal-to-noise ratio in the awake but not anesthetized state. This methodology is applicable to other brain regions, and will be useful for studying cortical activity and plasticity in marmosets during learning, development, and in neurological disorders. PMID:27786241

  4. Defective insulin secretion by chronic glucagon receptor activation in glucose intolerant mice.

    PubMed

    Ahlkvist, Linda; Omar, Bilal; Valeur, Anders; Fosgerau, Keld; Ahrén, Bo

    2016-03-01

    Stimulation of insulin secretion by short-term glucagon receptor (GCGR) activation is well characterized; however, the effect of long-term GCGR activation on β-cell function is not known, but of interest, since hyperglucagonemia occurs early during development of type 2 diabetes. Therefore, we examined whether chronic GCGR activation affects insulin secretion in glucose intolerant mice. To induce chronic GCGR activation, high-fat diet fed mice were continuously (2 weeks) infused with the stable glucagon analog ZP-GA-1 and challenged with oral glucose and intravenous glucose±glucagon-like peptide 1 (GLP1). Islets were isolated to evaluate the insulin secretory response to glucose±GLP1 and their pancreas were collected for immunohistochemical analysis. Two weeks of ZP-GA-1 infusion reduced insulin secretion both after oral and intravenous glucose challenges in vivo and in isolated islets. These inhibitory effects were corrected for by GLP1. Also, we observed increased β-cell area and islet size. We conclude that induction of chronic ZP-GA-1 levels in glucose intolerant mice markedly reduces insulin secretion, and thus, we suggest that chronic activation of the GCGR may contribute to the failure of β-cell function during development of type 2 diabetes.

  5. [Unpredictable chronic mild stress effects on antidepressants activities in forced swim test].

    PubMed

    Kudryashov, N V; Kalinina, T S; Voronina, T A

    2015-02-01

    The experiments has been designed to study unpredictable chronic mild stress effect on anti-depressive activities of amitriptyline (10 mg/kg) and fluoxetine (20 mg/kg) in forced swim test in male outbred mice. It is shown that acute treatment with fluoxetine does not produce any antidepressant effects in mice following stress of 14 days while the sub-chronic injections of fluoxetine result in more deep depressive-like behavior. In 28 daily stressed mice, antidepressant effect of fluoxetine is observed independently of the injection rates. Amitriptyline demonstrates the antidepressant activity regardless of the duration of stress or administration scheduling, but at the same time the severity of anti-immobilization effect of amitriptyline in stressed mice is weaker in compare to non-stressed trails. Thus, the injection rates and duration of unpredictable mild chronic stress are the parameters that determine the efficiency of antidepressants in the mouse forced swimming test.

  6. Immune Activation and Cardiovascular Disease in Chronic HIV Infection

    PubMed Central

    Longenecker, Chris T.; Sullivan, Claire; Baker, Jason V.

    2016-01-01

    Purpose of review To describe the potential contribution of immune activation in the pathogenesis of HIV-associated cardiovascular disease (CVD)—a leading cause of morbidity and mortality among HIV positive persons with access to antiretroviral therapy (ART). Recent findings We review recent literature that suggests abnormalities in both adaptive and innate immunity contributes to CVD risk among persons with HIV infection. In particular, potentially atherogenic T-cell mechanisms include persistent high-level T-cell activation (and associated pro-inflammatory mechanisms), as well as the presence of co-pathogens (e.g., CMV) providing an ongoing stimulus for cytotoxic T-cell responses. More recent data has then emphasized the potential impact of monocyte/macrophage-mediated inflammation and injury within atherosclerotic lesions. The pathology driving innate immune activation many not fully reverse with ART treatment, highlighting the need for interventions that target inflammation as a CVD prevention strategy. Summary Premature CVD among persons with HIV infection is due, in part, to persistent abnormalities in immune activation and systemic inflammation despite viral suppression. Prevention strategies for persons with HIV infection include those that target traditional CVD risk factors as well as newer candidate treatments with potential immunomodulatory benefits. PMID:26599166

  7. Unraveling dynamics of human physical activity patterns in chronic pain conditions

    NASA Astrophysics Data System (ADS)

    Paraschiv-Ionescu, Anisoara; Buchser, Eric; Aminian, Kamiar

    2013-06-01

    Chronic pain is a complex disabling experience that negatively affects the cognitive, affective and physical functions as well as behavior. Although the interaction between chronic pain and physical functioning is a well-accepted paradigm in clinical research, the understanding of how pain affects individuals' daily life behavior remains a challenging task. Here we develop a methodological framework allowing to objectively document disruptive pain related interferences on real-life physical activity. The results reveal that meaningful information is contained in the temporal dynamics of activity patterns and an analytical model based on the theory of bivariate point processes can be used to describe physical activity behavior. The model parameters capture the dynamic interdependence between periods and events and determine a `signature' of activity pattern. The study is likely to contribute to the clinical understanding of complex pain/disease-related behaviors and establish a unified mathematical framework to quantify the complex dynamics of various human activities.

  8. Chronic hyperammonemia alters the circadian rhythms of corticosteroid hormone levels and of motor activity in rats.

    PubMed

    Ahabrach, Hanan; Piedrafita, Blanca; Ayad, Abdelmalik; El Mlili, Nisrin; Errami, Mohammed; Felipo, Vicente; Llansola, Marta

    2010-05-15

    Patients with liver cirrhosis may present hepatic encephalopathy with a wide range of neurological disturbances and alterations in sleep quality and in the sleep-wake circadian rhythm. Hyperammonemia is a main contributor to the neurological alterations in hepatic encephalopathy. We have assessed, in an animal model of chronic hyperammonemia without liver failure, the effects of hyperammonemia per se on the circadian rhythms of motor activity, temperature, and plasma levels of adrenal corticosteroid hormones. Chronic hyperammonemia alters the circadian rhythms of locomotor activity and of cortisol and corticosterone levels in blood. Different types of motor activity are affected differentially. Hyperammonemia significantly alters the rhythm of spontaneous ambulatory activity, reducing strongly ambulatory counts and slightly average velocity during the night (the active phase) but not during the day, resulting in altered circadian rhythms. In contrast, hyperammonemia did not affect wheel running at all, indicating that it affects spontaneous but not voluntary activity. Vertical activity was affected only very slightly, indicating that hyperammonemia does not induce anxiety. Hyperammonemia abolished completely the circadian rhythm of corticosteroid hormones in plasma, completely eliminating the peaks of cortisol and corticosterone present in control rats at the start of the dark period. The data reported show that chronic hyperammonemia, similar to that present in patients with liver cirrhosis, alters the circadian rhythms of corticosteroid hormones and of motor activity. This suggests that hyperammonemia would be a relevant contributor to the alterations in corticosteroid hormones and in circadian rhythms in patients with liver cirrhosis.

  9. Vigorous-intensity leisure-time physical activity and risk of major chronic disease in men

    PubMed Central

    Chomistek, Andrea K.; Cook, Nancy R.; Flint, Alan J.; Rimm, Eric B.

    2012-01-01

    Purpose Although studies have shown health benefits for moderate-intensity physical activity, there is limited evidence to support beneficial effects for high amounts of vigorous activity among middle-aged and older men. The objective of this study was to examine the relationship between vigorous-intensity physical activity, compared to moderate-intensity activity, and risk of major chronic disease in men. Methods We prospectively examined the associations between vigorous- and moderate-intensity physical activity and risk of major chronic disease among 44,551 men aged 40–75 years in 1986. Leisure-time physical activity was assessed biennially by questionnaire. During 22 years of follow-up, we documented 14,162 incident cases of major chronic disease, including 4769 cardiovascular events, 6449 cancer events, and 2944 deaths from other causes. Results The hazard ratio (HR) of major chronic disease comparing ≥ 21 to 0 MET-hours/week of exercise was 0.86 (95% CI: 0.81, 0.91) for vigorous-intensity activity and 0.85 (95% CI: 0.80, 0.90) for moderate activity. For CVD, the corresponding HR were 0.78 (95% CI: 0.70, 0.86) and 0.80 (95% CI: 0.72, 0.88), respectively. When examined separately, running, tennis, and brisk walking were inversely associated with CVD risk. Furthermore, more vigorous activity was associated with lower disease risk; the HR comparing >70 to 0 MET-hours/week of vigorous-intensity exercise was 0.79 (95% CI: 0.68, 0.92; P <0.0001 for trend) for major chronic disease and 0.73 (95% CI: 0.56, 0.96; P <0.0001 for trend) for CVD. Conclusions Vigorous- and moderate-intensity physical activity were associated with lower risk of major chronic disease and cardiovascular disease. Increasing amounts of vigorous activity remained inversely associated with disease risk, even among men in the highest categories of exercise. PMID:22543741

  10. Changes in Muscle Activation after Reach Training with Gravity Compensation in Chronic Stroke Patients

    ERIC Educational Resources Information Center

    Prange, Gerdienke B.; Krabben, Thijs; Renzenbrink, Gerbert J.; Ijzerman, Maarten J.; Hermens, Hermie J.; Jannink, Michiel J. A.

    2012-01-01

    The objective of this study is to examine the effect of gravity compensation training on reaching and underlying changes in muscle activation. In this clinical trial, eight chronic stroke patients with limited arm function received 18 sessions (30 min) of gravity-compensated reach training (during 6 weeks) in combination with a rehabilitation…

  11. Web-Based Self-Management in Chronic Care: A Study of Change in Patient Activation

    ERIC Educational Resources Information Center

    Solomon, Michael R.

    2010-01-01

    Web-based self-management interventions (W-SMIs) are designed to help a large number of chronically ill people become more actively engaged in their health care. Despite the potential to engage more patients in self-managing their health, the use of W-SMIs by patients and their clinicians is low. Using a self-management conceptual model based on…

  12. Association between Therapy Outcome and Right-Hemispheric Activation in Chronic Aphasia

    ERIC Educational Resources Information Center

    Richter, Maria; Miltner, Wolfgang H. R.; Straube, Thomas

    2008-01-01

    The role of the right hemisphere for language processing and successful therapeutic interventions in aphasic patients is a matter of debate. This study explored brain activation in right-hemispheric areas and left-hemispheric perilesional areas in response to language tasks in chronic non-fluent aphasic patients before and after constraint-induced…

  13. Chronic active interstitial pancreatitis as a cause of transverse colonic obstruction and colic in a horse

    PubMed Central

    Lohmann, Katharina L.; Allen, Andrew L.

    2015-01-01

    A mature Quarter horse was euthanized following colic of 3 days duration. Postmortem, the large intestine, except the descending colon, was diffusely distended and associated with adhesion of the transverse colon to the pancreas, which had changes consistent with chronic active interstitial pancreatitis. Other lesions included hepatic fibrosis, erosive gastritis, and bilateral adrenal cortical hyperplasia. PMID:26538675

  14. Giant cell arteritis associated with chronic active Epstein-Barr virus infection.

    PubMed

    Giardina, A; Rizzo, A; Ferrante, A; Capra, G; Triolo, G; Ciccia, F

    2013-03-28

    Giant cell arteritis is an inflammatory vasculopathy that preferentially affects medium-sized and large arteries. A viral cause has been suspected but not confirmed in polymyalgia rheumatica and giant-cell arteritis. We report the case of a 81-year-old female who suffered from chronic active Epstein-Barr virus infection and developed giant cell temporal arteritis.

  15. Chronic Enhancement of CREB Activity in the Hippocampus Interferes with the Retrieval of Spatial Information

    ERIC Educational Resources Information Center

    Viosca, Jose; Malleret, Gael; Bourtchouladze, Rusiko; Benito, Eva; Vronskava, Svetlana; Kandel, Eric R.; Barco, Angel

    2009-01-01

    The activation of cAMP-responsive element-binding protein (CREB)-dependent gene expression is thought to be critical for the formation of different types of long-term memory. To explore the consequences of chronic enhancement of CREB function on spatial memory in mammals, we examined spatial navigation in bitransgenic mice that express in a…

  16. Activation symptoms and discharge in elderly chronic schizophrenic inpatients.

    PubMed

    White, Leonard; Opler, Lewis A; Harvey, Philip D; Parrella, Michael; Friedman, Joseph I

    2004-12-01

    Three hundred thirty-three elderly schizophrenic inpatients were rated on the Positive and Negative Syndrome Scale (PANSS), and those remaining in the hospital after 1 year (N = 267) were rated and followed for an additional year. Based on previous studies showing that aggressive episodes and hostile behavior predicted inability to discharge schizophrenics, we hypothesized that low discharge rates would be correlated with high baseline ratings on the activation factor of the PANSS (PANSS-AF), obtained by summing six items (hostility, poor impulse control, excitement, uncooperativeness, poor rapport, and tension). Baseline PANSS-AF scores were found to be inversely correlated with discharge rates, independent of ratings on other symptom dimensions. PANSS-AF scores were a better predictor of outcome than any individual PANSS item (e.g., hostility), and individual item scores did not add significantly to prediction of discharge. Attention to and development of treatments for activation symptoms, highly prevalent in schizophrenia but not included in our present diagnostic systems, may increase the chances of elderly inpatients with schizophrenia of moving to community settings.

  17. Effects of acute and chronic uremia on active cation transport in rat myocardium

    SciTech Connect

    Druml, W.; Kelly, R.A.; England, B.K.; O'Hara, D.S.; Mitch, W.E. )

    1990-12-01

    As abnormalities of active cation transport could contribute to the genesis of uremic cardiomyopathy, we investigated myocardial sodium pump function in rats with acute renal failure (ARF) and with a model of experimental chronic renal failure (CRF) that has metabolic similarities to advanced chronic uremia in humans. CRF rats were hypertensive and had left ventricular hypertrophy (33% higher heart:body weight ratio; P less than 0.01) at four weeks compared to pair-fed sham-operated rats. Importantly, both ouabain- and furosemide-sensitive 86Rb uptake rates were unchanged in left ventricular myocardial slices from CRF, and the intracellular sodium concentration was not different from that of control rats even though skeletal muscle sodium was increased, as we found previously. Insulin-stimulated, ouabain-sensitive 86Rb influx was also preserved. There also were no abnormalities in myocardium cation transport in rats with ARF. However, (3H)ouabain binding was decreased 45% in CRF rats (P less than 0.01); it was unchanged in acute uremia. Decreased ouabain binding in chronic uremia was due entirely to fewer low affinity (3H)ouabain binding sites (the binding affinity for ouabain was unaffected). We conclude that in chronic, (but not acute) renal failure, sodium pump number is reduced in myocardium but intracellular sodium is unchanged and active cation flux rates are maintained. These results emphasize that in rats with chronic uremia, intracellular sodium homeostasis is preserved in myocardium, despite the presence of marked abnormalities of active cation transport in skeletal muscle that are characteristic of chronic uremia.

  18. Chronic alcohol consumption enhances iNKT cell maturation and activation

    SciTech Connect

    Zhang, Hui Zhang, Faya; Zhu, Zhaohui; Luong, Dung; Meadows, Gary G.

    2015-01-15

    Alcohol consumption exhibits diverse effects on different types of immune cells. NKT cells are a unique T cell population and play important immunoregulatory roles in different types of immune responses. The effects of chronic alcohol consumption on NKT cells remain to be elucidated. Using a mouse model of chronic alcohol consumption, we found that alcohol increases the percentage of NKT cells, especially iNKT cells in the thymus and liver, but not in the spleen or blood. Alcohol consumption decreases the percentage of NK1.1{sup −} iNKT cells in the total iNKT cell population in all of the tissues and organs examined. In the thymus, alcohol consumption increases the number of NK1.1{sup +}CD44{sup hi} mature iNKT cells but does not alter the number of NK1.1{sup −} immature iNKT cells. A BrdU incorporation assay shows that alcohol consumption increases the proliferation of thymic NK1.1{sup −} iNKT cells, especially the NK1.1{sup −}CD44{sup lo} Stage I iNKT cells. The percentage of NKG2A{sup +} iNKT cells increases in all of the tissues and organs examined; whereas CXCR3{sup +} iNKT cells only increases in the thymus of alcohol-consuming mice. Chronic alcohol consumption increases the percentage of IFN-γ-producing iNKT cells and increases the blood concentration of IFN-γ and IL-12 after in vivo α-galactosylceramide (αGalCer) stimulation. Consistent with the increased cytokine production, the in vivo activation of iNKT cells also enhances the activation of dendritic cells (DC) and NK, B, and T cells in the alcohol-consuming mice. Taken together the data indicate that chronic alcohol consumption enhances iNKT cell maturation and activation, which favors the Th1 immune response. - Highlights: • Chronic alcohol consumption increases iNKT cells in the thymus and liver • Chronic alcohol consumption enhances thymic Stage I iNKT cell proliferation • Chronic alcohol consumption enhances iNKT cell maturation in thymus and periphery • Chronic alcohol

  19. Use of Narrow Band Imaging in the Diagnosis of Hypovascular Endobronchial Sarcoidosis.

    PubMed

    Hakim, Rimoun; Sabath, Bruce; Kaplan, Tugba; Yung, Rex

    2017-02-08

    Narrow band imaging (NBI) has been widely applied for the evaluation of numerous disease conditions that present with increased vascularity of the mucosa, most often malignancies. It is increasingly being used in benign conditions as well. We present the first case in which NBI was used, rather, to detect areas of bronchial hypovascularity due to its ability to increase the visual contrast between normal and hypovascular mucosa. Endobronchial biopsy of these nodules led to the diagnosis of sarcoidosis. Had conventional white light alone been utilized, the diagnosis would likely have been missed because not only were these lesions difficult to visualize under white light but transbronchial lung biopsy and transbronchial needle aspiration were unremarkable. We propose that NBI should be considered in the bronchoscopic evaluation of possible sarcoidosis or any other condition that could present with airway hypovascularity.

  20. Gallium-67 scintigraphy, bronchoalveolar lavage, and pathologic changes in patients with pulmonary sarcoidosis

    SciTech Connect

    Abe, S.; Munakata, M.; Nishimura, M.; Tsuneta, Y.; Terai, T.; Nakano, I.; Ohsaki, Y.; Kawakami, Y.

    1984-05-01

    The intensity of gallium-67 scintiscans, lymphocyte counts in bronchoalveolar lavage fluid, and pathologic changes were studied in 26 patients with untreated pulmonary sarcoidosis. Noncaseating granulomas were recognized with significantly greater frequency in stage 2 (80 percent; 8/10 cases) than in stage 1 (43 percent; 6/14 cases). Alveolitis showed little relation to the roentgenographic stage. There was a strong correlation between the intensity of gallium uptake in pulmonary parenchyma and the detection rate of granuloma; however, the detection rate of alveolitis was not statistically different from the intensity of gallium uptake. A highly significant correlation was revealed between the lymphocyte counts in bronchoalveolar lavage fluid and the intensity of alveolitis. These observations suggest that the gallium uptake reflects mainly the presence of granuloma, and the lymphocyte count in bronchoalveolar lavage fluid reflects the intensity of alveolitis in patients with pulmonary sarcoidosis.

  1. Dementia, gait disturbance, and urinary incontinence in a patient with pulmonary sarcoidosis.

    PubMed

    Labarca, Gonzalo; Ramirez, Romina; Monsalve, Ximena; Mira-Avendano, Isabel

    2016-09-01

    Hydrocephalus is an uncommon presentation of neurosarcoidosis. We discuss the case of a 67-year-old woman with a prior diagnosis of hypothyroidism, systemic hypertension, and lung sarcoidosis who presented with a 1-month history of progressive impairment of consciousness leading to prostration and loss of sphincter control. At admission, patient was febrile with altered speech and without focalization. Laboratory results showed leucocytosis and mild anaemia. Cerebrospinal fluid (CSF) analysis was characterized by mild elevated protein level, increased cell count, normal glucose and adenosine deaminase (ADA), negative cytology, and no bacterial isolations. Electroencephalogram showed toxic-metabolic encephalopathy. Computed tomography (CT) of the brain revealed hydrocephalus without structural damage, and magnetic resonance imaging of the brain demonstrated non-specific diffuse meningeal enhancement and periventricular changes supporting normal pressure hydrocephalus. Chest X-ray showed mediastinal adenopathy and parenchymatous lesions, consistent with stage II lung sarcoidosis. A ventriculoperitoneal shunt was installed, and the patient experienced rapid improvement in her symptoms.

  2. Gastric involvement of sarcoidosis in a patient with multiple lung nodules

    PubMed Central

    Ceylan, Emel; Şen, Serdar; Coşkun, Adil; Meteoğlu, İbrahim; Demirtaş, Nimet; Çildağ, Orhan

    2015-01-01

    Sarcoidosis is a granulomatous disorder mostly could involve intrathoracic structures. The gastric involvement is rare and the symptoms may be non-specific. We herein report a case of a 56-year-old female patient who was admitted due to chest tightness and discomfort. Computed tomography (CT) of the thorax revealed bilaterally nodular lesions in the lower lobes of the lung and pleural effusion on the left side. Positron emission tomography/CT showed lung nodules and gastric involvement with mesenteric lymphadenomegalies with pathological uptake of 18F-fluoro-2-deoxy-d-glucose. Pathological examination of the lung biopsy taken by thoracotomy demonstrated non-caseating granulomas. The gastric biopsies taken by endoscopy also showed non-caseating granulomas consistent with a diagnosis of sarcoidosis. PMID:26487882

  3. Physical activity for the prevention and treatment of major chronic disease: an overview of systematic reviews

    PubMed Central

    2013-01-01

    Background The evidence that higher levels of physical activity and/or lower levels of physical inactivity are associated with beneficial health-related outcomes stems mainly from observational studies. Findings from these studies often differ from randomised controlled trials and systematic reviews currently demonstrate mixed results, due partly to heterogeneity in physical activity interventions, methodologies used and populations studied. As a result, translation into clinical practice has been difficult. It is therefore essential that an overview is carried out to compare and contrast systematic reviews, and to identify those physical activity interventions that are the most effective in preventing and/or treating major chronic disease. This protocol has been registered on PROSPERO 2013: CRD42013003523. Methods We will carry out an overview of Cochrane systematic reviews. We will search the Cochrane Database of Systematic Reviews for systematic reviews of randomised controlled trials that have a primary focus on disease-related outcomes. We will restrict reviews to those in selected major chronic diseases. Two authors will independently screen search outputs, select studies, extract data and assess the quality of included reviews using the assessment of multiple systematic reviews tool; all discrepancies will be resolved by discussing and reaching a consensus, or by arbitration with a third author. The data extraction form will summarise key information from each review, including details of the population(s) (for example, disease condition), the context (for example, prevention, treatment or management), the participants, the intervention(s), the comparison(s) and the outcomes. The primary outcomes of interest are the prevention of chronic disease and/or improved outcomes, in the treatment or management of chronic disease. These outcomes will be summarised and presented for individual chronic diseases (for example, any change in blood pressure in hypertension

  4. Prostate-Specific Membrane Antigen PET/CT: False-Positive Results due to Sarcoidosis?

    PubMed Central

    Hermann, Robert M.; Djannatian, Manoutschehr; Czech, Norbert; Nitsche, Mirko

    2016-01-01

    We report on a 72-year-old male patient who developed sarcoidosis of the mediastinal lymph nodes, the liver, and the prostate 11 years ago. Seven years later, he underwent transurethral resection of the prostate by laser due to hematuria. Pathology of the resected chips showed a ‘granulomatous prostatitis with epitheloid cells’. Malignancy was histologically excluded at that time. Four years later, he was diagnosed with an undifferentiated prostate carcinoma, with a Gleason score of 5 + 4 = 9. After initiation of antihormonal therapy, he underwent radical prostatectomy and pelvic lymphadenectomy, which revealed a pT3b pN1 carcinoma with infiltrated resection margins. Three months later, the prostate-specific antigen level was 1.4 ng/ml, and a local recurrence was suspected by ultrasound; consequently, a 68Ga-prostate-specific membrane antigen (PSMA) PET/CT was performed. This examination seemed to confirm the local recurrence, a right pelvic lymph node metastasis, and a hepatic metastasis. However, ultrasound with contrast medium could not confirm the metastatic spread to the liver. In palliative intention, radiotherapy of the pelvis was done. After 50 Gy, the supposed recurrence had markedly shrunk, and an additional boost dose with 16.2 Gy was applied. Two years later, the patient is still free of disease. Due to this clinical development, we doubt the diagnosis of a fulminant progression of the prostate cancer as suspected by PSMA-PET/CT. Instead, we suspect a recurrence of the previously proven sarcoidosis leading to false-positive results. Our focus in this report is on the interaction between PSMA-PET/CT and sarcoidosis. Another report on a case of sarcoidosis of the spleen seems to confirm this possibility [Kobe et al: Clin Nucl Med 2015;40: 897–898]. PMID:27721768

  5. The Kmif (Kveim-induced macrophage migration inhibition factor) test in sarcoidosis

    PubMed Central

    Williams, W. Jones; Pioli, E.; Jones, D. J.; Dighero, M.

    1972-01-01

    Circulating lymphocytes from 30 patients with sarcoidosis when stimulated in vitro with Kveim-induced macrophage migration factor, the Kmif test, produced a guinea-pig macrophage migration inhibition factor in 21 of 30 cases (70%). In those patients not on steroids the results showed a good correlation with the cutaneous Kveim test. One positive test was found in 16 normal subjects. Our results suggest that the Kmif test may prove a useful rapid alternative to the Kveim test. PMID:4675181

  6. Increased CD45RO expression on T lymphocytes in mediastinal lymph node and pulmonary lesions of patients with pulmonary sarcoidosis.

    PubMed Central

    Fazel, S B; Howie, S E; Krajewski, A S; Lamb, D

    1994-01-01

    Sarcoidosis is characterized by a cell-mediated response mediated by the activation of CD4+ T lymphocytes in an environment lacking adequate numbers of regulatory CD8+ T lymphocytes. Immunohistological studies on frozen tissues have shown that sarcoid lesions have activated CD4 helper/inducer T lymphocytes at the centre of granulomata, whereas lymphocytes at the periphery are mainly CD8 suppressor/cytotoxic cells. In this study we investigated the immunohistological distribution of CD45 isoforms of T cells in 29 paraffin-embedded sarcoid lesions in mediastinal and open lung biopsies. Ten of these were assessed quantitatively, with single-staining of serial sections demonstrating a predominance of CD45RO memory T lymphocytes in granulomata and intergranulomatous areas. Ratios of CD45RO:CD45RA T lymphocytes (or the ratio of memory to naive T cells) were 42.0:1 for granulomata and 17.9:1 for intergranulomatous areas of sarcoid lesions counted. This finding is compatible with the hypothesis that nearly all the lymphocytes present in sarcoid lesions have been previously activated, and selectively home to sarcoid lesions. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:8137547

  7. Activation of chronic toxoplasmosis by transportation stress in a mouse model.

    PubMed

    Shen, Bang; Yuan, Yuan; Cheng, Jianxi; Pan, Ming; Xia, Ningbo; Zhang, Weichao; Wang, Yifan; Zhou, Yanqin; Zhao, Junlong

    2016-12-27

    Toxoplasma gondii is an obligate intracellular parasite infecting 25% of the world population and enormous number of animals. It can exist in two forms in intermediate hosts: the fast replicating tachyzoites responsible for acute infection and the slowly replicating bradyzoites responsible for life-long chronic infection. The interconversion between tachyzoites and bradyzoites plays critical roles in the transmission and pathogenesis of T. gondii. However, the molecular mechanisms that govern the interconversion are largely unknown. In this study, we established a chronic infection model in mice and examined the impact of transportation stress on the status of chronic infection. Our results demonstrated that, treating chronically infected mice with conditions mimicking transportation stress reduced the levels of several key cytokines that restrict the infection at chronic stage. Increased expression of the tachyzoite specific gene SAG1 (surface antigen 1) was detected in brain cysts of stress treated mice, indicating activation and conversion of bradyzoites to tachyzoites. Using this model, we identified fifteen toxoplasmic proteins that had significant abundance changes during stress induced cysts reactivation. These proteins serve as a basis for further investigation of the mechanisms governing bradyzoite conversion.

  8. Activation of chronic toxoplasmosis by transportation stress in a mouse model

    PubMed Central

    Shen, Bang; Yuan, Yuan; Cheng, Jianxi; Pan, Ming; Xia, Ningbo; Zhang, Weichao; Wang, Yifan; Zhou, Yanqin; Zhao, Junlong

    2016-01-01

    Toxoplasma gondiiis an obligate intracellular parasite infecting 25% of the world population and enormous number of animals. It can exist in two forms in intermediate hosts: the fast replicating tachyzoites responsible for acute infection and the slowly replicating bradyzoites responsible for life-long chronic infection. The interconversion between tachyzoites and bradyzoites plays critical roles in the transmission and pathogenesis of T. gondii. However, the molecular mechanisms that govern the interconversion are largely unknown. In this study, we established a chronic infection model in mice and examined the impact of transportation stress on the status of chronic infection. Our results demonstrated that, treating chronically infected mice with conditions mimicking transportation stress reduced the levels of several key cytokines that restrict the infection at chronic stage. Increased expression of the tachyzoite specific gene SAG1 (surface antigen 1) was detected in brain cysts of stress treated mice, indicating activation and conversion of bradyzoites to tachyzoites. Using this model, we identified fifteen toxoplasmic proteins that had significant abundance changes during stress induced cysts reactivation. These proteins serve as a basis for further investigation of the mechanisms governing bradyzoite conversion. PMID:27895319

  9. Bronchoalveolar mast cells in sarcoidosis: increased numbers and accentuation of mediator release.

    PubMed Central

    Flint, K C; Leung, K B; Hudspith, B N; Brostoff, J; Pearce, F L; Geraint-James, D; Johnson, N M

    1986-01-01

    Bronchoalveolar lavage was carried out in 36 subjects with sarcoidosis and 20 control subjects undergoing bronchoscopy for routine diagnostic purposes. The proportion of mast cells in the lavage fluid of subjects with sarcoidosis (mean (SE) 0.84% 0.09%; p less than 0.01) when compared with that of controls (mean 0.32% (0.05%); p less than 0.01). This increase was greatest in subjects with positive gallium scans but was not correlated with the percentage recovery of lymphocytes or radiographic stage. Anti-IgE induced histamine release from the bronchoalveolar cells of 15 subjects with sarcoidosis was significantly increased at all effective doses of anti-IgE. This accentuation of histamine release was significantly greater in patients with positive gallium scans and correlated directly with the percentage recovery of lymphocytes (r = 0.7, p less than 0.005). The dose-response curve of anti-IgE induced histamine release from bronchoalveolar cells of subjects with more than 20% of lymphocytes in the lavage cell population was significantly greater than the dose-response curves of subjects with fewer than 20% of lymphocytes and of controls. PMID:2422776

  10. Prostacyclin and Oral Vasodilator Therapy in Sarcoidosis-Associated Pulmonary Hypertension

    PubMed Central

    Oldham, Justin M.; Gomberg-Maitland, Mardi; Vij, Rekha

    2015-01-01

    BACKGROUND: It is unclear whether recent advances in pulmonary arterial hypertension therapy can be safely applied to sarcoidosis-associated pulmonary hypertension (SAPH). Evidence for prostacyclin (PG) therapy in SAPH is limited. METHODS: We conducted a single-center, retrospective review of 46 patients with sarcoidosis, 26 of whom had SAPH. Thirteen received PG as monotherapy or in combination with oral vasodilators. RESULTS: Follow-up right-sided heart catheterization at a mean of 12.7 months revealed improved cardiac output, cardiac index, and pulmonary vascular resistance. Functional class and N-terminal pro-brain natriuretic peptide levels also improved in patients treated with PG. No significant change in oxygen requirement was seen with vasodilator therapy initiation. At 2 years, 15 patients with SAPH survived, including eight on PG, and at 5 years, seven survived, including five on PG. Survival was significantly reduced in patients with SAPH compared with patients who had sarcoidosis without pulmonary hypertension. Multivariate analysis demonstrated that the use of PG therapy in SAPH is not associated with increased mortality. CONCLUSIONS: Many patients with severe SAPH showed significant hemodynamic and clinical improvement on long-term IV or subcutaneous PG therapy and had survival outcomes similar to patients with moderate SAPH on oral vasodilator therapy. PMID:26437815

  11. Pitfalls of contrast-enhanced ultrasound (CEUS) in the diagnosis of splenic sarcoidosis.

    PubMed

    Tana, C; Iannetti, G; D'Alessandro, P; Tana, M; Mezzetti, A; Schiavone, C

    2013-01-01

    By observing the real-time behavior of focal liver lesions at three vascular phases (arterial, portal-venous, and late), contrast-enhanced ultrasound (CEUS) has been successfully applied to differentiate benign from malignant hepatic nodules. In recent years, numerous studies highlighted the usefulness of CEUS also for other applications such as abdominal trauma, renal, pancreatic, thyroid, and inflammatory bowel diseases, supporting its role even in differentiating benign from malignant splenic nodules. Therefore, the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) recently updated the guidelines for the use of ultrasound contrast agents in clinical practice, pointing out the indication to characterize splenic parenchymal inhomogeneity or suspected lesions found on conventional ultrasound (BUS). We describe the case of a patient with a history of colon cancer and finding, at BUS and CEUS, of hypoechoic lesions with a highly suggestive pattern for metastases, subsequently histologically proved to be splenic localizations of a benign and multisystemic granulomatous disease such as sarcoidosis. We therefore reviewed the current literature focusing on the role of CEUS in differentiating benign from malignant splenic lesions, emphasizing on the lack of data and numerical shortage of sarcoidosis derived-lesions in the available studies. We conclude that sarcoidosis remains a diagnosis of exclusion and new studies are needed before defining precise indications of CEUS in these patients.

  12. Sarcoidosis: correlation of pulmonary parenchymal pattern at CT with results of pulmonary function tests

    SciTech Connect

    Bergin, C.J.; Bell, D.Y.; Coblentz, C.L.; Chiles, C.; Gamsu, G.; MacIntyre, N.R.; Coleman, R.E.; Putman, C.E.

    1989-06-01

    The appearances of the lungs on radiographs and computed tomographic (CT) scans were correlated with degree of uptake on gallium scans and results of pulmonary function tests (PFTs) in 27 patients with sarcoidosis. CT scans were evaluated both qualitatively and quantitatively. Patients were divided into five categories on the basis of the pattern of abnormality at CT: 1 = normal (n = 4); 2 = segmental air-space disease (n = 4); 3 = spherical (alveolar) masslike opacities (n = 4); 4 = multiple, discrete, small nodules (n = 6); and 5 = distortion of parenchymal structures (fibrotic end-stage sarcoidosis) (n = 9). The percentage of the volume judged to be abnormal (CT grade) was correlated with PFT results for each CT and radiographic category. CT grades were also correlated with gallium scanning results and percentage of lymphocytes recovered from bronchoalveolar lavage (BAL). Patients in CT categories 1 and 2 had normal lung function, those in category 3 had mild functional impairment, and those in categories 4 and 5 showed moderate to severe dysfunction. The overall CT grade correlated well with PFT results expressed as a percentage of the predicted value. In five patients, CT scans showed extensive parenchymal disease not seen on radiographs. CT grades did not correlate with the results of gallium scanning or BAL lymphocytes. The authors conclude that patterns of parenchymal sarcoidosis seen at CT correlate with the PFT results and can be used to indicate respiratory impairment.

  13. Nucleus accumbens neuronal activity correlates to the animal's behavioral response to acute and chronic methylphenidate.

    PubMed

    Claussen, Catherine M; Chong, Samuel L; Dafny, Nachum

    2014-04-22

    Acute and chronic methylphenidate (MPD) exposure was recorded simultaneously for the rat's locomotor activity and the nucleus accumbens (NAc) neuronal activity. The evaluation of the neuronal events was based on the animal's behavior response to chronic MPD administration: 1) Animals exhibiting behavioral sensitization, 2) Animals exhibiting behavioral tolerance. The experiment lasted for 10days with four groups of animals; saline, 0.6, 2.5, and 10.0mg/kg MPD. For the main behavioral findings, about half of the animals exhibited behavioral sensitization or behavioral tolerance to 0.6, 2.5, and/or 10mg/kg MPD respectively. Three hundred and forty one NAc neuronal units were evaluated. Approximately 80% of NAc units responded to 0.6, 2.5, and 10.0mg/kg MPD. When the neuronal activity was analyzed based on the animals' behavioral response to chronic MPD exposure, significant differences were seen between the neuronal population responses recorded from animals that expressed behavioral sensitization when compared to the NAc neuronal responses recorded from animals exhibiting behavioral tolerance. Three types of neurophysiological sensitization and neurophysiological tolerance can be recognized following chronic MPD administration to the neuronal populations. Collectively, these findings show that the same dose of chronic MPD can elicit either behavioral tolerance or behavioral sensitization. Differential statistical analyses were used to verify our hypothesis that the neuronal activity recorded from animals exhibiting behavioral sensitization will respond differently to MPD compared to those animals exhibiting behavioral tolerance, thus, suggesting that it is essential to record the animal's behavior concomitantly with neuronal recordings.

  14. Sarcoidosis exclusion criteria: the “simple truth” for a “complicated diagnosis”.

    PubMed

    Tchernev, G; Chokoeva, A A; Schiavone, C; D Erme, A M; Tana, C; Darling, M; Kaley, J; Gianfaldoni, S; Wollina, U; Lotti, T; Patterson, J W

    2015-01-01

    The differentiation between sarcoidosis and sarcoid-type reactions remains a clinical and histopathologic diagnostic dilemma. A definitive distinction is yet to be determined according to the current literature data. Sarcoid-like tissue reactions with identifiable infectious or other immunogenic antigens, should be classified as non-specific clinical manifestations of a specific disease. The current assignment of this type of reaction under the generic umbrella of “sarcoidosis” is incorrect and may result in the subsequent misinterpretation of the definition of the disease in general. On the other hand, this may lead to clinical studies with incorrectly selected inclusion criteria and, therefore, contradictory statements regarding the epidemiology and pathogenesis of the disease. Thus we propose the introduction of new criteria for exclusion of sarcoidosis as an autonomous disease. Recent trials on patients with probable sarcoidosis have focused on ideal criteria, or have provided information about the genetic and immunological profile of patients with specific infections or other diseases, which manifest themself as sarcoidal granulomas. This could explain the heterogeneous clinical and/or genetic profiles of the reported patients, who in fact were not affected by the autonomous disease “sarcoidosis”. The simplification of the current available data regarding this issue will be of fundamental importance for the correct direction of future studies, whose aim is to unravel the pathogenesis of the immunological cascade in patients with sarcoidosis and sarcoid-like type of reaction. It is expected that the introduction of exclusion criteria will inevitably lead to a change in the approach to diagnosis as well as the fundamental understanding of this mysterious disease, known as sarcoidosis.

  15. Sarcoidosis-Associated Aortoesophageal Fistula-Multistage Interdisciplinary Surgical Therapy for a Rare and Life-Threatening Condition.

    PubMed

    Gombert, Alexander; Grommes, Jochen; Schick, Guido; Binnebösel, Marcel; Klink, Christian; Jacobs, Michael J; Kotelis, Drosos

    2017-02-01

    Aortoesophageal fistulas (AEFs) are rare and life-threatening conditions. Till date, an association between an AEF and sarcoidosis has not been reported yet. The aim of this report is to demonstrate a case of AEF secondary to sarcoidosis and its multistage interdisciplinary surgical therapy. A 66-year-old male was diagnosed with sarcoidosis in 2014. He has been treated with glucocorticoids since then and no severe health restrictions due to the disease have occurred. In December 2015, the patient presented with acute thoracic pain and hematemesis: an esophagogastroscopy revealed an AEF. First, stent-graft implantation in the thoracic aorta was urgently performed as a "bridging" procedure. Second, esophagectomy and local debridement were performed, followed by explantation of the stent graft and reconstruction by means of xenograft replacement of the stented aorta in a third operation. Finally, retrosternal gastric pull-up was performed in a fourth operative procedure. Sixteen days after the last operation the patient could be discharged to a rehabilitation clinic. Follow-up is uneventful so far; the antibiotic therapy was stopped at the time of hospital discharge. The pathogenesis of sarcoidosis, a rare autoimmunological disease, has not been completely clarified yet. The diagnosis relies on clinical symptoms and radiological as well as histopathological findings. Many cases of sarcoidosis show spontaneous regression, but severe complications may occur. While tracheoesophageal fistulas have been described in the literature, AEFs related to sarcoidosis have not been mentioned yet. Despite surgical and antibiotic treatment, the morbidity and mortality rates of AEF are high. Because the endovascular treatment has been established for emergency procedures of the aorta, it is considered as an appropriate first-line "bridging" treatment option. To achieve good long-term results, surgical treatment has to involve esophagectomy with secondary reconstruction of the upper

  16. Recovery of network-driven glutamatergic activity in rat hippocampal neurons during chronic glutamate receptor blockade.

    PubMed

    Leininger, Eric; Belousov, Andrei B

    2009-01-28

    Previous studies indicated that a long-term decrease in the activity of ionotropic glutamate receptors induces cholinergic activity in rat and mouse hypothalamic neuronal cultures. Here we studied whether a prolonged inactivation of ionotropic glutamate receptors also induces cholinergic activity in hippocampal neurons. Receptor activity was chronically suppressed in rat hippocampal primary neuronal cultures with two proportionally increasing sets of concentrations of NMDA plus non-NMDA receptor antagonists: 100 microM/10 microM AP5/CNQX (1X cultures) and 200 microM/20 microM AP5/CNQX (2X cultures). Using calcium imaging we demonstrate that cholinergic activity does not develop in these cultures. Instead, network-driven glutamate-dependent activity, that normally is detected in hyper-excitable conditions, reappears in each culture group in the presence of these antagonists and can be reversibly suppressed by higher concentrations of AP5/CNQX. This activity is mediated by non-NMDA receptors and is modulated by NMDA receptors. Further, non-NMDA receptors, the general level of glutamate receptor activity and CaMK-dependent signaling are critical for development of this network-driven glutamatergic activity in the presence of receptor antagonists. Using electrophysiology, western blotting and calcium imaging we show that some neuronal parameters are either reduced or not affected by chronic glutamate receptor blockade. However, other parameters (including neuronal excitability, mEPSC frequency, and expression of GluR1, NR1 and betaCaMKII) become up-regulated and, in some cases, proportionally between the non-treated, 1X and 2X cultures. Our data suggest recovery of the network-driven glutamatergic activity after chronic glutamate receptor blockade. This recovery may represent a form of neuronal plasticity that compensates for the prolonged suppression of the activity of glutamate receptors.

  17. Effect of acute vs chronic H2O2-induced oxidative stress on antioxidant enzyme activities.

    PubMed

    Miguel, Fernanda; Augusto, Amanda C; Gurgueira, Sonia A

    2009-04-01

    H2O2 can freely crosses membranes and in the presence of Fe2+ (or Cu+) it is prone to participate in Fenton reaction. This study evaluated the concentration and time-dependent effects of H2O2-induced oxidative stress on MnSOD, Se:GPx and catalase and on aconitase. Acute and chronic H2O2 treatments were able to induce oxidative stress in HeLa cells as they significantly decreased aconitase activity and also caused a very significant decrease on antioxidant enzyme activities. The inhibition of enzyme activities was time- and concentration-dependent. Chronic treatment with 5 microM H2O2/h after 24 h was able to decrease all enzyme activities almost at the same level as the acute treatment. Acute and chronic treatments on antioxidant enzyme activities were prevented by cell treatment with ascorbic acid or N-acetylcysteine. These results indicate that antioxidant enzymes can also be affected by the same ROS they produce or neutralize if the time of exposure is long enough.

  18. Activation of autophagy induces retinal ganglion cell death in a chronic hypertensive glaucoma model

    PubMed Central

    Park, H-Y Lopilly; Kim, J H; Park, C K

    2012-01-01

    Autophagy is reported to have important roles in relation to regulated cell death pathways and neurodegeneration. This study used chronic hypertensive glaucoma rat model to investigate whether the autophagy pathway has a role in the apoptosis of retinal ganglion cells (RGCs) after chronic intraocular pressure (IOP) elevation. Under electron microscopy, autophagosomes were markedly accumulated in the dendrites and cytoplasm of RGCs after IOP elevation. Western blot analysis showed that LC3-II/LC3-I and beclin-1 were upregulated throughout the 8-weeks period after IOP elevation. The pattern of LC3 immunostaining showed autophagy activation in the cytoplasm of RGCs to increase and peak at 4 weeks after IOP elevation. Most of these LC3B-positive RGCs underwent apoptosis by terminal deoxynucleotidyltransferase-mediated biotinylated UTP nick end labeling, and inhibition of autophagy with 3-methyladenine decreased RGC apoptosis. The activated pattern shows that autophagy is initially activated in the dendrites of the RGCs, but, thereafter autophagy is mainly activated in the cytoplasm of RGCs. This may show that autophagy is differently regulated in different compartments of the neuron. This present study showed that autophgy is activated in RGCs and has a role in autophagic cell death after chronic IOP elevation. PMID:22476098

  19. Proteolytic activity is altered in brain tissue of rats upon chronic exposure to ozone

    SciTech Connect

    Benuck, M.; Banay-Schwartz, M.; Lajtha, A. )

    1993-01-01

    Tissue from pons medulla of rats exposed in vivo to various levels of ozone was assayed for calpain and cathepsin D activity. Chronic exposure to ozone increased calpain activity, which was 35% to 46% higher in the homogenates of animals exposed to 1.0 ppm ozone than in those of animals exposed to 0.5 ppm ozone or of controls. An increase in activity of 26% was also observed in the soluble supernatant. The increase in activity did not seem to be caused by ozone effects on calpastatin. Addition of 32 mM carnitine to the incubation mixture increased total activity 3-4 fold, making the differences in activity proportionately smaller. Cathepsin D activity was little altered. Changes in calpain activity and in the generation of free oxygen radicals have been implicated in the aging process, long-term exposure to ozone may magnify changes. Ozone exposure may cause changes in brain protein metabolism. 15 refs., 2 tabs.

  20. Altered activation patterns by triceps surae stretch reflex pathways in acute and chronic spinal cord injury.

    PubMed

    Frigon, Alain; Johnson, Michael D; Heckman, C J

    2011-10-01

    Spinal reflexes are modified by spinal cord injury (SCI) due the loss of excitatory inputs from supraspinal structures and changes within the spinal cord. The stretch reflex is one of the simplest pathways of the central nervous system and was used presently to evaluate how inputs from primary and secondary muscle spindles interact with spinal circuits before and after spinal transection (i.e., spinalization) in 12 adult decerebrate cats. Seven cats were spinalized and allowed to recover for 1 mo (i.e., chronic spinal state), whereas 5 cats were evaluated before (i.e., intact state) and after acute spinalization (i.e., acute spinal state). Stretch reflexes were evoked by stretching the left triceps surae (TS) muscles. The force evoked by TS muscles was recorded along with the activity of several hindlimb muscles. Stretch reflexes were abolished in the acute spinal state due to an inability to activate TS muscles, such as soleus (Sol) and lateral gastrocnemius (LG). In chronic spinal cats, reflex force had partly recovered but Sol and LG activity remained considerably depressed, despite the fact that injecting clonidine could recruit these muscles during locomotor-like activity. In contrast, other muscles not recruited in the intact state, most notably semitendinosus and sartorius, were strongly activated by stretching TS muscles in chronic spinal cats. Therefore, stretch reflex pathways from TS muscles to multiple hindlimb muscles undergo functional reorganization following spinalization, both acute and chronic. Altered activation patterns by stretch reflex pathways could explain some sensorimotor deficits observed during locomotion and postural corrections after SCI.

  1. Effect of acute and chronic administration of methamphetamine on activator protein-1 binding activities in the rat brain regions.

    PubMed

    Akiyama, K; Ishihara, T; Kashihara, K

    1996-10-31

    The activator protein-1 (AP-1) binding activities in the three brain regions (striatum, nucleus accumbens, cingulate cortex) increased after a single methamphetamine (METH, 4 mg/kg) injection and reached maximum levels after 180 min. Pretreatment with SCH 23390 (0.5 mg/kg), a selective dopamine D1 receptor antagonist, significantly inhibited the enhanced AP-1 binding activities induced by acute METH (4 mg/kg) administration. In chronic experiments, rats were pretreated with METH (4 mg/kg) or saline for 14 days. The AP-1 binding activities after a 1-week abstinence from chronic administration of MAP increased significantly in all the brain regions compared with those of the saline-treated controls, whereas after a 4-week abstinence, the AP-1 binding activity decreased significantly in the cingulate cortex, but not striatum or nucleus accumbens, compared with the saline-treated control group. A METH challenge after a 4-week abstinence period induced significantly more intense stereotypy, but lower AP-1 binding activities in all the brain regions of rats treated with repeated METH than repeated saline injections. The super-shift assay revealed that after a 1- or 4-week abstinence, there was no significant difference between the Fos-related antigens (Fras) contents of the saline- and METH-treated groups in any brain region examined, and that the Jun family protein levels of the METH-treated group increased significantly in the striatum and nucleus accumbens after a 1-, but not 4-, week abstinence. These results suggest that chronic METH administration leads to delayed decay of the induced AP-1 binding activities and Jun component levels after abstinence for up to 1 week, but results in no change in or decreases these activities and attenuates METH challenge-induced AP-1 binding activities after abstinence for 4 weeks.

  2. A New Measure for Assessing the Physical Activity Behaviors of Persons with Disabilities and Chronic Health Conditions: The Physical Activity and Disability Survey.

    ERIC Educational Resources Information Center

    Rimmer, James H.; Riley, Barth B.; Rubin, Stephen S.

    2001-01-01

    Assessed the psychometric properties of the Physical Activity and Disability Survey (PADS), which measures physical activity for people with disabilities and chronic health conditions. Cross-sectional and pre-post designs were employed with 103 people who had disabilities and chronic health conditions. Results supported the PADS' reliability and…

  3. Myocardial performance index for detection of subclinical abnormalities in patients with sarcoidosis

    PubMed Central

    Simsek, Zuhal; Sarli, Bahadir; Buyukoglan, Hakan

    2014-01-01

    Aim The aim of this study was to evaluate ventricular functions in patients with sarcoidosis without an obvious heart disease by using tissue Doppler-derived left and right ventricular myocardial performance index (MPI). Methods The study population included 45 patient with sarcoidosis (29 men, 16 women; mean age, 44±10 years, mean disease duration, 4.2±2.7 years) and 45 healthy control subjects (31 men, 14 women; mean age, 41±8 years). Cardiac functions were determined using echocardiography, consisting of standard two-dimensional and conventional Doppler and tissue Doppler imaging (TDI). Myocardial tissue Doppler velocities [peak systolic (Sa), early diastolic (Ea), and late diastolic velocities (Aa)] were recorded using spectral pulsed Doppler from the LV free wall, septum, and RV free wall from the apical four chamber view. MPI was also calculated by TDI. Results The conventional echocardiographic parameters and tissue Doppler measurements were similar between the patients and controls. Left ventricular MPI (0.490±0.092 vs. 0.396±0.088, P=0.010) and right ventricular MPI (0.482±0.132 vs. 0.368±0.090, P=0.006) were significantly higher in patients with sarcoidosis than the control subjects. There was a correlation between the disease duration and right and left ventricular MPI (r=0.418, P=0.005; r=0.366, P=0.013, respectively). There was also a correlation between the systolic pulmonary arterial pressure and right ventricular MPI but not left ventricular MPI (r=0.370, P=0.012; r=0.248, P=0.109, respectively). In receiver operating characteristics curve analysis, the cutoff value of left ventricular MPI >0.46 had 92% sensitivity and 64% specificity in predicting left ventricular diastolic dysfunction. Conclusions We have demonstrated that tissue Doppler-derived myocardial left and right ventricular MPI were impaired in sarcoidosis patients, although systolic function parameters were comparable in the patients and controls, showed a subclinic impaired

  4. [Adapted Physical Activity for patients with chronic diseases in a therapeutic community].

    PubMed

    Bouricha, Rémy; Thöni, Gilles; Raffard, Laurence; Cochet, Laurence; Saucourt, Vincent; Tirode, Véronique

    2015-01-01

    The French therapeutic communities ("Appartements de Coordination Therapeutique (ACT)") are mostly members of the "National Federation of Accommodation for HIV+ and other chronic diseases. They provide accommodation for people living with chronic conditions (HIV hepatitis, cancers...) and in a situation of high psychosocial frailty. As a result of their coordinated multidisciplinary intervention, these structures provide the required support to access health care and facilitate social inclusion. They are designed to provide an appropriate response to people with cumulative medical and social conditions (chronic diseases, precariousness, addictions and other comorbidities). Our innovative local experiment integrates Adapted Physical Activities (APA) into the global medical and social follow-up, in line with the patient's individual health care project. The characteristics of each APA project (nature of the activities proposed, intensity, duration, frequency, individual vs. team activity and accompanying methods) are defined on an individual basis, according to the user's motivations and inputs from the support team (medical, psychological and social coordination). The follow-up ensured by our APA professionals allows the residents to participate in a regular and attractive physical activity and could contribute to their social inclusion. The multidisciplinary approach proposed by ACTs determines the beneficial effects observed in such vulnerable patients.

  5. Chronic enhancement of CREB activity in the hippocampus interferes with the retrieval of spatial information.

    PubMed

    Viosca, Jose; Malleret, Gaël; Bourtchouladze, Rusiko; Benito, Eva; Vronskava, Svetlana; Kandel, Eric R; Barco, Angel

    2009-03-01

    The activation of cAMP-responsive element-binding protein (CREB)-dependent gene expression is thought to be critical for the formation of different types of long-term memory. To explore the consequences of chronic enhancement of CREB function on spatial memory in mammals, we examined spatial navigation in bitransgenic mice that express in a regulated and restricted manner a constitutively active form of CREB, VP16-CREB, in forebrain neurons. We found that chronic enhancement of CREB activity delayed the acquisition of an allocentric strategy to solve the hidden platform task. The ability to turn on and off transgene expression allowed us to dissect the role of CREB in dissociable memory processes. In mice in which transgene expression was turned on during memory acquisition, turning off the transgene re-established the access to the memory trace, whereas in mice in which transgene expression was turned off during acquisition, turning on the transgene impaired memory expression in a reversible manner, indicating that CREB enhancement specifically interfered with the retrieval of spatial information. The defects on spatial navigation in mice with chronic enhancement of CREB function were not corrected by conditions that increased further CREB-dependent activation of hippocampal memory systems, such as housing in an enriched environment. These results along with previous findings in CREB-deficient mutants indicate that the relationship of CREB-mediated plasticity to spatial memory is an inverted-U function, and that optimal learning in the water maze requires accurate regulation of this pathway.

  6. [Measurement of physical activity in patients with chronic obstructive pulmonary disease].

    PubMed

    Magnussen, Helgo; Waschki, Benjamin; Watz, Henrik

    2009-04-15

    Physical activity is an important parameter related to morbidity and mortality in cardiovascular disease, metabolic syndrome/diabetes, mental disorders, cancer, and chronic obstructive pulmonary disease (COPD). In COPD, lower levels of physical activity as reported by the patients are associated with a faster annual lung function decline, increased number of hospitalizations, and higher risk of mortality. Self-reported physical activity, however, correlates only poorly with objectively quantified physical activity in patients with COPD. Recent data show that physical activity can reliably be measured in a substantial number of patients with COPD. Extrapulmonary effects of COPD are associated with reduced physical activity. Clinical characteristics commonly used to assess disease severity like the forced expiratory volume in 1 s or the 6-min walk distance only incompletely reflect the physical activity of patients with COPD.

  7. Pulmonary mucosa-associated lymphoid tissue lymphoma associated with pulmonary sarcoidosis: a case report and literature review.

    PubMed

    Kokuho, Nariaki; Terasaki, Yasuhiro; Urushiyama, Hirokazu; Terasaki, Mika; Kunugi, Shinobu; Morimoto, Taisuke; Azuma, Arata; Usuda, Jitsuo; Gemma, Akihiko; Eishi, Yoshinobu; Shimizu, Akira

    2016-05-01

    Differentiating low-grade lymphoma from preexisting sarcoidosis is difficult because of their pathological similarity. This article describes a case of pulmonary mucosa-associated lymphoid tissue lymphoma associated with pulmonary sarcoidosis. The patient, a 45-year-old Japanese man, presented with a 10-year history of pulmonary sarcoidosis and 5-year history of ocular sarcoidosis with histologic findings. Because only the right S3 lung nodule had gradually enlarged, partial resection was performed. Pathological study revealed noncaseous epithelioid granulomas with lymphoplasmacytic proliferation but also marked lymphoid cell proliferation with lymphoepithelial lesion findings that differed from findings of typical sarcoid lesions. Our lymphoepithelial lesion evaluation via immunohistochemistry and analysis of Ig heavy-chain gene rearrangements with assessment of Propionibacterium acnes-specific antibody reactions allow us to report, for the first time, this case of pulmonary mucosa-associated lymphoid tissue lymphoma associated with pulmonary sarcoidosis in exactly the same location, which may be significant for differentiating these diseases and understanding their pathogenic association.

  8. Activating chronic kidney disease patients and family members through the Internet to promote integration of care

    PubMed Central

    Trisolini, Michael; Roussel, Amy; Zerhusen, Eileen; Schatell, Dorian; Harris, Shelly; Bandel, Karen; Salib, Philip; Klicko, Kristi

    2004-01-01

    Abstract Purpose To describe the potential role of the Internet as a vehicle for improving integration of care through activating chronic kidney disease patients and their family members. Also, to describe how that potential is being developed through a website sponsored by the Medicare program in the United States. Background The Internet is expanding at a rapid rate, and health-related websites are one of its most popular features. Efforts to promote integration of care have focused mainly on providers up to now, and more emphasis is needed on the potential roles of patients. Chronically ill patients have particular needs for improved education about their conditions and enhanced involvement in care planning and treatment decisions. Medicare developed the Dialysis Facility Compare website to serve those goals for people with chronic kidney disease. Methods We conducted qualitative research with 140 chronic kidney disease patients and family members, and 130 renal care professionals to evaluate and improve the Dialysis Facility Compare website. A series of 19 focus groups, 13 triads (small focus groups), and 56 individual interviews were conducted in four regions of the United States and by telephone. Results We found that the Dialysis Facility Compare website has the potential to improve integration of care for people with chronic kidney disease in at least three ways. First: by expanding the roles of patients as members of the multi-disciplinary team of caregivers treating their disease. Second: through better integration of the informal care provided in the home and community with the formal care provided by health professionals. Third: by improving coordination of between care provided in the pre-dialysis and dialysis phases of the disease. Discussion We developed recommendations for revising and enhancing the Dialysis Facility Compare website in a number of ways to better promote patient activation and integration of care. The unique features of the Internet

  9. Macrophage activation associated with chronic murine cytomegalovirus infection results in more severe experimental choroidal neovascularization.

    PubMed

    Cousins, Scott W; Espinosa-Heidmann, Diego G; Miller, Daniel M; Pereira-Simon, Simone; Hernandez, Eleut P; Chien, Hsin; Meier-Jewett, Courtney; Dix, Richard D

    2012-01-01

    The neovascular (wet) form of age-related macular degeneration (AMD) leads to vision loss due to choroidal neovascularization (CNV). Since macrophages are important in CNV development, and cytomegalovirus (CMV)-specific IgG serum titers in patients with wet AMD are elevated, we hypothesized that chronic CMV infection contributes to wet AMD, possibly by pro-angiogenic macrophage activation. This hypothesis was tested using an established mouse model of experimental CNV. At 6 days, 6 weeks, or 12 weeks after infection with murine CMV (MCMV), laser-induced CNV was performed, and CNV severity was determined 4 weeks later by analysis of choroidal flatmounts. Although all MCMV-infected mice exhibited more severe CNV when compared with control mice, the most severe CNV developed in mice with chronic infection, a time when MCMV-specific gene sequences could not be detected within choroidal tissues. Splenic macrophages collected from mice with chronic MCMV infection, however, expressed significantly greater levels of TNF-α, COX-2, MMP-9, and, most significantly, VEGF transcripts by quantitative RT-PCR assay when compared to splenic macrophages from control mice. Direct MCMV infection of monolayers of IC-21 mouse macrophages confirmed significant stimulation of VEGF mRNA and VEGF protein as determined by quantitative RT-PCR assay, ELISA, and immunostaining. Stimulation of VEGF production in vivo and in vitro was sensitive to the antiviral ganciclovir. These studies suggest that chronic CMV infection may serve as a heretofore unrecognized risk factor in the pathogenesis of wet AMD. One mechanism by which chronic CMV infection might promote increased CNV severity is via stimulation of macrophages to make pro-angiogenic factors (VEGF), an outcome that requires active virus replication.

  10. Impact of sustained virus elimination on natural anticoagulant activity in patients with chronic viral hepatitis C.

    PubMed

    Saray, Aida; Mesihović, Rusmir; Vukobrat-Bijedić, Zora; Gornjaković, Srđan; Vanis, Nenad; Mehmedović, Amila; Papović, Vedad; Glavaš, Sanjin

    2013-05-01

    Previous studies have reported reduced synthesis of various hemostatic factors in patients with chronic liver disease. Whether changes in plasma levels of these proteins reflect recovered liver synthetic function following virological eradication therapy has not been approved yet. The aim of the study was to determine the impact of sustained viral suppression achieved with pegylated interferon alpha and ribavirin on hemostatic parameters including natural anticoagulants in patients with chronic hepatitis C. The following coagulation screening tests were obtained in thirty patients with chronic viral hepatitis C before and after completion of antiviral treatment: activated partial thromboplastin time, prothrombin time, plasma fibrinogen and natural anticoagulant proteins antithrombin III, protein C (PC) and total protein S (PS) activity. Only patients who achieved durable virus suppression were included. The mean PC and PS levels were significantly lower in patients with chronic viral hepatitis C before antiviral therapy than in healthy controls (79.04 ± 16.19 % vs. 109.92 ± 21.33% and 54.04 ± 16.11% vs. 87.60 ± 8.15%, respectively; (p<0.001). Mean levels of PC exhibited a significant increase by 14.69 % after the completion of antiviral treatment (93.73 ± 14.18%, p<0.001) as well as PS levels, which significantly increased by 21.46% (75.50 ± 15.43, p<0.001) when compared with pre-treatment values. No remarkable fluctuations in other hemostatic parameters were noted. Protein C and protein S are sensitive markers of hepatocyte synthetic impairment and are valuable markers in monitoring the efficacy of antiviral treatment in chronic hepatitis C patients. Larger studies are needed to confirm our results.

  11. Chronic social isolation reduces 5-HT neuronal activity via upregulated SK3 calcium-activated potassium channels

    PubMed Central

    Sargin, Derya; Oliver, David K; Lambe, Evelyn K

    2016-01-01

    The activity of serotonin (5-HT) neurons is critical for mood regulation. In a mouse model of chronic social isolation, a known risk factor for depressive illness, we show that 5-HT neurons in the dorsal raphe nucleus are less responsive to stimulation. Probing the responsible cellular mechanisms pinpoints a disturbance in the expression and function of small-conductance Ca2+-activated K+ (SK) channels and reveals an important role for both SK2 and SK3 channels in normal regulation of 5-HT neuronal excitability. Chronic social isolation renders 5-HT neurons insensitive to SK2 blockade, however inhibition of the upregulated SK3 channels restores normal excitability. In vivo, we demonstrate that inhibiting SK channels normalizes chronic social isolation-induced anxiety/depressive-like behaviors. Our experiments reveal a causal link for the first time between SK channel dysregulation and 5-HT neuron activity in a lifelong stress paradigm, suggesting these channels as targets for the development of novel therapies for mood disorders. DOI: http://dx.doi.org/10.7554/eLife.21416.001 PMID:27874831

  12. Effect of Citrocard on functional activity of cardiomyocyte mitochondria during chronic alcohol intoxication.

    PubMed

    Perfilova, V N; Ostrovskii, O V; Verovskii, V E; Popova, T A; Lebedeva, S A; Dib, H

    2007-03-01

    Chronic administration of 50% ethanol in a dose of 8 g/kg produces a toxic effect on functional activity of cardiomyocyte mitochondria, which manifested in decreased rates of respiration and oxidative phosphorylation. Structural GABA analogue Citrocard (phenibut citrate) and reference preparation piracetam in doses of 50 and 200 mg/kg, respectively, prevented the damaging effect of alcohol, which was seen from increased indexes of oxidative phosphorylation in treated animals compared to the control group.

  13. Neutrophil proteolytic activation cascades: a possible mechanistic link between chronic periodontitis and coronary heart disease.

    PubMed

    Alfakry, Hatem; Malle, Ernst; Koyani, Chintan N; Pussinen, Pirkko J; Sorsa, Timo

    2016-01-01

    Cardiovascular diseases are chronic inflammatory diseases that affect a large segment of society. Coronary heart disease (CHD), the most common cardiovascular disease, progresses over several years and affects millions of people worldwide. Chronic infections may contribute to the systemic inflammation and enhance the risk for CHD. Periodontitis is one of the most common chronic infections that affects up to 50% of the adult population. Under inflammatory conditions the activation of endogenous degradation pathways mediated by immune responses leads to the release of destructive cellular molecules from both resident and immigrant cells. Matrix metalloproteinases (MMPs) and their regulators can activate each other and play an important role in immune response via degrading extracellular matrix components and modulating cytokines and chemokines. The action of MMPs is required for immigrant cell recruitment at the site of inflammation. Stimulated neutrophils represent the major pathogen-fighting immune cells that upregulate expression of several proteinases and oxidative enzymes, which can degrade extracellular matrix components (e.g. MMP-8, MMP-9 and neutrophil elastase). The activity of MMPs is regulated by endogenous inhibitors and/or candidate MMPs (e.g. MMP-7). The balance between MMPs and their inhibitors is thought to mirror the proteolytic burden. Thus, neutrophil-derived biomarkers, including myeloperoxidase, may activate proteolytic destructive cascades that are involved in subsequent immune-pathological events associated with both periodontitis and CHD. Here, we review the existing studies on the contribution of MMPs and their regulators to the infection-related pathology. Also, we discuss the possible proteolytic involvement and role of neutrophil-derived enzymes as an etiological link between chronic periodontitis and CHD.

  14. Physical activity and sedentary behaviour: applying lessons to chronic obstructive pulmonary disease.

    PubMed

    Hill, K; Gardiner, P A; Cavalheri, V; Jenkins, S C; Healy, G N

    2015-05-01

    In health and disease, the benefits of regular participation in moderate to vigorous intensity physical activity are well documented. However, individuals with chronic conditions, such as those with chronic obstructive pulmonary disease (COPD), typically do very little activity at a moderate or vigorous intensity. Much of their day is instead spent in sedentary behaviour, such as sitting or reclining, which requires very little energy expenditure. This high level of time spent in sedentary behaviour can have serious health consequences, including increased risk of diabetes, cardiovascular disease and premature mortality. There is emerging evidence to suggest that participation in light intensity physical activities (e.g. standing or slow walking) may have benefits for cardio-metabolic health. Given the low aerobic capacity of individuals with moderate to severe COPD, increasing light intensity activity (through reducing sedentary time) may be a feasible additional strategy to improve health in this population, alongside traditional recommendations to increase the time spent in moderate to vigorous intensity physical activity. This review provides an overview of physical activity and sedentary behaviour, with a particular emphasis on these behaviours for people with COPD. It provides suggestions for the measurement of these behaviours within the clinical setting, as well as for interventions that may be effective at increasing physical activity and reducing sedentary behaviour in this population.

  15. Rationale and Design of the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis Study. Alpha-1 Protocol.

    PubMed

    Strange, Charlie; Senior, Robert M; Sciurba, Frank; O'Neal, Scott; Morris, Alison; Wisniewski, Stephen R; Bowler, Russell; Hochheiser, Harry S; Becich, Michael J; Zhang, Yingze; Leader, Joseph K; Methé, Barbara A; Kaminski, Naftali; Sandhaus, Robert A

    2015-10-01

    Severe deficiency of alpha-1 antitrypsin has a highly variable clinical presentation. The Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis α1 Study is a prospective, multicenter, cross-sectional study of adults older than age 35 years with PiZZ or PiMZ alpha-1 antitrypsin genotypes. It is designed to better understand if microbial factors influence this heterogeneity. Clinical symptoms, pulmonary function testing, computed chest tomography, exercise capacity, and bronchoalveolar lavage (BAL) will be used to define chronic obstructive pulmonary disease (COPD) phenotypes that can be studied with an integrated systems biology approach that includes plasma proteomics; mouth, BAL, and stool microbiome and virome analysis; and blood microRNA and blood mononuclear cell RNA and DNA profiling. We will rely on global genome, transcriptome, proteome, and metabolome datasets. Matched cohorts of PiZZ participants on or off alpha-1 antitrypsin augmentation therapy, PiMZ participants not on augmentation therapy, and control participants from the Subpopulations and Intermediate Outcome Measures in COPD Study who match on FEV1 and age will be compared. In the primary analysis, we will determine if the PiZZ individuals on augmentation therapy have a difference in lower respiratory tract microbes identified compared with matched PiZZ individuals who are not on augmentation therapy. By characterizing the microbiome in alpha-1 antitrypsin deficiency (AATD), we hope to define new phenotypes of COPD that explain some of the diversity of clinical presentations. As a unique genetic cause of COPD, AATD may inform typical COPD pathogenesis, and better understanding of it may illuminate the complex interplay between environment and genetics. Although the biologic approaches are hypothesis generating, the results may lead to development of novel biomarkers, better understanding of COPD phenotypes, and development of novel diagnostic and therapeutic trials in AATD and COPD

  16. Patients with chronic pain may need extra support when prescribed physical activity in primary care: a qualitative study

    PubMed Central

    Joelsson, Monica; Bernhardsson, Susanne; Larsson, Maria E. H.

    2017-01-01

    Background Physical activity plays an important role in the prevention and treatment of chronic musculoskeletal pain, but chronic pain may implicate a poor rehabilitation outcome. The concept of physical activity on prescription (PAP) is a therapeutic option for various diseases, but there is a lack of knowledge about how patients with chronic musculoskeletal pain experience receiving the prescription. Objectives The objective of this study was to describe the experiences of and thoughts about receiving a prescription for physical activity of people with chronic musculoskeletal pain. Design Interviews analysed using qualitative content analysis with an inductive approach. Setting Three primary healthcare centres in a mixed rural and suburban area in the vicinity of a large city in western Sweden. Subjects Fifteen individuals with chronic musculoskeletal pain. Results Four categories were identified with the overarching theme “Physical activity in chronic pain requires extra support”. There were several barriers for increasing activity level and these patients suffered from the additional burden of pain. The categories were: “Important to identify needs”, “Barriers and facilitators for physical activity”, “Perceptions of PAP vary” and “Effects found of receiving PAP”. Conclusions Despite the many positive experiences of receiving PAP, patients described confusion about the role and execution of PAP. Chronic pain is an additional barrier for increasing activity level, and it is crucial to consider these patients’ circumstances. This study suggests that patients with chronic musculoskeletal pain have a greater need for information and extra support to overcome existing barriers, before or when physical activity is prescribed. Key Points Physical activity is important for prevention and treatment of chronic pain and has earlier been shown to be increased by “physical activity on prescription”. Patients with chronic musculoskeletal pain

  17. Sleep is associated with task-negative brain activity in fibromyalgia participants with comorbid chronic insomnia

    PubMed Central

    Vatthauer, Karlyn E; Craggs, Jason G; Robinson, Michael E; Staud, Roland; Berry, Richard B; Perlstein, William M; McCrae, Christina S

    2015-01-01

    Patients with chronic pain exhibit altered default mode network (DMN) activity. This preliminary project questioned whether comorbid disease states are associated with further brain alterations. Thirteen women with fibromyalgia (FM) only and 26 women with fibromyalgia with comorbid chronic insomnia (FMI) underwent a single night of ambulatory polysomnography and completed a sleep diary each morning for 14 days prior to performing a neuroimaging protocol. Novel imaging analyses were utilized to identify regions associated with significantly disordered sleep that were more active in task-negative periods than task-oriented periods in participants with FMI, when compared to participants with FM. It was hypothesized that core DMN areas (ie, cingulate cortex, inferior parietal lobule, medial prefrontal cortex, medial temporal cortex, precuneus) would exhibit increased activity during task-negative periods. Analyses revealed that significantly disordered sleep significantly contributed to group differences in the right cingulate gyrus, left lentiform nucleus, left anterior cingulate, left superior gyrus, medial frontal gyrus, right caudate, and the left inferior parietal lobules. Results suggest that FMI may alter some brain areas of the DMN, above and beyond FM. However, future work will need to investigate these results further by controlling for chronic insomnia only before conclusions can be made regarding the effect of FMI comorbidity on the DMN. PMID:26648751

  18. Fatigue, anxiety and depression levels, activities of daily living of patients with chronic obstructive pulmonary disease.

    PubMed

    Karakurt, Papatya; Ünsal, Ayla

    2013-04-01

    The aim of this cross-sectional study was to determine the fatigue, anxiety and depression levels, activities of daily living of patients with chronic obstructive pulmonary disease (n = 255). It was found that there was significant difference between Visual Analogue Scale for Fatigue (VAS-F) point averages and gender, education levels, marital status and economical status of patient with chronic obstructive pulmonary disease. Among the participants in this study, 36.5% had an anxiety disorder whereas 69.0% exhibited depression. In the study, it was determined that 85.5% of those were independent in their Katz's Index of Activities of Daily Living (ADLs) and 49.4% of those were independent in their Lawton and Brody's Index of Instrumental Activities of Daily Living (IADLs). This study has shown that VAS-F, the Hospital Anxiety and Depression Scale, ADL and IADL instruments that measure the various aspects of health-related quality of living can contribute considerably to a more diversified understanding of the patients' situation with chronic obstructive pulmonary disease.

  19. Alterations in fear conditioning and amygdalar activation following chronic wheel running in rats.

    PubMed

    Burghardt, Paul R; Pasumarthi, Ravi K; Wilson, Marlene A; Fadel, Jim

    2006-06-01

    Several convergent lines of evidence point to the amygdala as a key site of plasticity underlying most forms of fear conditioning. Studies have shown that chronic physical activity, such as wheel running, can alter learning in a variety of contexts, including aversive conditioning. The ability of chronic wheel running (WR) to alter both behavioral correlates of fear conditioning and indices of amygdalar activation, however, has not been simultaneously assessed. Here, rats were given constant access to either free-turning or--as a control--locked (LC) running wheels in their home cages. After 8 weeks of housing under these conditions, animals were exposed to a series of shocks in a separate testing chamber. Twenty-four hours later, the animals were returned to the shock chamber and freezing behavior was measured as an indicator of contextual fear conditioning. The animals were then sacrificed and their brains processed for immunohistochemical detection of Fos to assess patterns of putative neuronal activation. WR rats spent significantly more time freezing than their LC counterparts upon return to the shock-paired context. The enhanced conditioned freezing response was most pronounced in animals showing high levels of nightly wheel running activity. WR animals also had significantly higher levels of neuronal activation, as indicated by Fos expression in the central nucleus of the amygdala, but less activation in the basolateral nucleus, compared to sedentary controls. These data demonstrate the ability of chronic physical activity to alter contextual fear conditioning and implicate the amygdala as a potential site of plasticity underlying this phenomenon.

  20. Developing an active implementation model for a chronic disease management program

    PubMed Central

    Smidth, Margrethe; Christensen, Morten Bondo; Olesen, Frede; Vedsted, Peter

    2013-01-01

    Background Introduction and diffusion of new disease management programs in healthcare is usually slow, but active theory-driven implementation seems to outperform other implementation strategies. However, we have only scarce evidence on the feasibility and real effect of such strategies in complex primary care settings where municipalities, general practitioners and hospitals should work together. The Central Denmark Region recently implemented a disease management program for chronic obstructive pulmonary disease (COPD) which presented an opportunity to test an active implementation model against the usual implementation model. The aim of the present paper is to describe the development of an active implementation model using the Medical Research Council’s model for complex interventions and the Chronic Care Model. Methods We used the Medical Research Council’s five-stage model for developing complex interventions to design an implementation model for a disease management program for COPD. First, literature on implementing change in general practice was scrutinised and empirical knowledge was assessed for suitability. In phase I, the intervention was developed; and in phases II and III, it was tested in a block- and cluster-randomised study. In phase IV, we evaluated the feasibility for others to use our active implementation model. Results The Chronic Care Model was identified as a model for designing efficient implementation elements. These elements were combined into a multifaceted intervention, and a timeline for the trial in a randomised study was decided upon in accordance with the five stages in the Medical Research Council’s model; this was captured in a PaTPlot, which allowed us to focus on the structure and the timing of the intervention. The implementation strategies identified as efficient were use of the Breakthrough Series, academic detailing, provision of patient material and meetings between providers. The active implementation model was

  1. Effects of Chronic Active Cannabis Use on Visuomotor Integration, in Relation to Brain Activation and Cortisol Levels

    PubMed Central

    King, G.R.; Ernst, T.; Deng, W.; Stenger, A.; Gonzales, R.M.K; Nakama, H.; Chang, L.

    2012-01-01

    Cannabis is the most abused illegal substance in the United States. Alterations in brain function and motor behavior have been reported in chronic cannabis users, but the results have been variable. The current study aimed to determine whether chronic active cannabis use in humans may alter psychomotor function, brain activation, and hypothalamic-pituitary-axis (HPA) function in men and women. 30 cannabis users (16 men and 14 women, 18 to 45 years old) and 30 non-drug user controls (16 men and 14 women, 19 to 44 years old) were evaluated with neuropsychological tests designed to assess motor behavior and functional MRI (fMRI), using a 3 Tesla scanner, during a visually paced finger-sequencing task, cued by a flashing checkerboard (at 2 or 4 Hz). Salivary cortisol was measured to assess HPA function. Male, but not female, cannabis users had significantly slower performance on psychomotor speed tests. As a group, cannabis users had greater activation in BA 6 than controls, while controls had greater activation in the visual area BA 17 than cannabis users. Cannabis users also had higher salivary cortisol levels than controls (p = 0.002). Chronic active cannabis use is associated with slower and less efficient psychomotor function, especially in the male users, as indicated by a shift from regions involved with automated visually guided responses to more executive or attentional control areas. These brain activities may be attenuated by the higher cortisol levels in the cannabis users which in turn may lead to less efficient visual-motor function. PMID:22159107

  2. Cytoskeletal protein Flightless (Flii) is elevated in chronic and acute human wounds and wound fluid: neutralizing its activity in chronic but not acute wound fluid improves cellular proliferation.

    PubMed

    Ruzehaji, Nadira; Grose, Randall; Krumbiegel, Doreen; Zola, Heddy; Dasari, Pallave; Wallace, Hilary; Stacey, Michael; Fitridge, Robert; Cowin, Allison J

    2012-01-01

    Chronic non-healing wounds form a medical need which will expand as the population ages and the obesity epidemic grows. Whilst the complex mechanisms underlying wound repair are not fully understood, remodelling of the actin cytoskeleton plays a critical role. Elevated expression of the actin cytoskeletal protein Flightless I (Flii) is known to impair wound outcomes. To determine if Flii is involved in the impaired healing observed in chronic wounds, its expression in non-healing human wounds from patients with venous leg ulcers was determined and compared to its expression in acute wounds and unwounded skin. Increased expression of Flii was observed in both chronic and acute wounds with wound fluid and plasma also containing secreted Flii protein. Inflammation is a key aspect of wound repair and fluorescence-activated cell sorting (FACS) analysis revealed Flii was located in neutrophils within the blood and that it co-localised with CD16+ neutrophils in chronic wounds. The function of secreted Flii was investigated as both chronic wound fluid and Flii have previously been shown to inhibit fibroblast proliferation. To determine if the inhibitory effect of wound fluid was due in part to the presence of Flii, wound fluids were depleted of Flii using Flii-specific neutralizing antibodies (FnAb). Flii depleted chronic wound fluid no longer inhibited fibroblast proliferation, suggesting that Flii may contribute to the inhibitory effect of chronic wound fluid on fibroblast function. Application of FnAbs to chronic wounds may therefore be a novel approach used to improve the local environment of non-healing wounds and potentially improve healing outcomes.

  3. Pulmonary Rehabilitation and Physical Activity in Patients with Chronic Obstructive Pulmonary Disease.

    PubMed

    Spruit, Martijn A; Pitta, Fabio; McAuley, Edward; ZuWallack, Richard L; Nici, Linda

    2015-10-15

    Physical inactivity is common in patients with chronic obstructive pulmonary disease (COPD) compared with age-matched healthy individuals or patients with other chronic diseases. Physical inactivity independently predicts poor outcomes across several aspects of this disease, but it is (at least in principle) treatable in patients with COPD. Pulmonary rehabilitation has arguably the greatest positive effect of any current therapy on exercise capacity in COPD; as such, gains in this area should facilitate increases in physical activity. Furthermore, because pulmonary rehabilitation also emphasizes behavior change through collaborative self-management, it may aid in the translation of increased exercise capacity to greater participation in activities involving physical activity. Both increased exercise capacity and adaptive behavior change are necessary to achieve significant and lasting increases in physical activity in patients with COPD. Unfortunately, it is readily assumed that this translation occurs naturally. This concise clinical review will focus on the effects of a comprehensive pulmonary rehabilitation program on physical activity in patients with COPD. Changing physical activity behavior in patients with COPD needs an interdisciplinary approach, bringing together respiratory medicine, rehabilitation sciences, social sciences, and behavioral sciences.

  4. Chronic Mild Stress Modulates Activity-Dependent Transcription of BDNF in Rat Hippocampal Slices.

    PubMed

    Molteni, Raffaella; Rossetti, Andrea C; Savino, Elisa; Racagni, Giorgio; Calabrese, Francesca

    2016-01-01

    Although activity-dependent transcription represents a crucial mechanism for long-lasting experience-dependent changes in the hippocampus, limited data exist on its contribution to pathological conditions. We aim to investigate the influence of chronic stress on the activity-dependent transcription of brain-derived neurotrophic factor (BDNF). The ex vivo methodology of acute stimulation of hippocampal slices obtained from rats exposed to chronic mild stress (CMS) was used to evaluate whether the adverse experience may alter activity-dependent BDNF gene expression. CMS reduces BDNF expression and that acute depolarization significantly upregulates total BDNF mRNA levels only in control animals, showing that CMS exposure may alter BDNF transcription under basal conditions and during neuronal activation. Moreover, while the basal effect of CMS on total BDNF reflects parallel modulations of all the transcripts examined, isoform-specific changes were found after depolarization. This different effect was also observed in the activation of intracellular signaling pathways related to the neurotrophin. In conclusion, our study discloses a functional alteration of BDNF transcription as a consequence of stress. Being the activity-regulated transcription a critical process in synaptic and neuronal plasticity, the different regulation of individual BDNF promoters may contribute to long-lasting changes, which are fundamental for the vulnerability of the hippocampus to stress-related diseases.

  5. Acute and Chronic Treatments with Quetiapine Increase Mitochondrial Respiratory Chain Complex Activity in the Rat Brain.

    PubMed

    Ignácio, Zuleide M; Réus, Gislaine Z; Abelaira, Helena M; Titus, Stephanie E; Carlessi, Anelise S; da Luz, Jaine R; Matias, Beatriz I; Bruchchen, Livia; Carvalho-Silva, Milena; Gomes, Lara M; Rebelo, Joyce; Streck, Emilio L; Quevedo, João

    2015-01-01

    Several studies have found that the molecular mechanisms of mitochondrial energy metabolism are impaired in major depressive disorder (MDD). Classic antidepressants and atypical antipsychotics can alter the function of enzymes involved in adenosine triphosphate (ATP) metabolism. Quetiapine is an atypical antipsychotic that, in addition to having a therapeutic benefit in treating MDD, appears to exert antioxidant and neuroprotective effects. Therefore, we aimed to evaluate the acute and chronic effects of quetiapine on the activity of enzyme complexes I to IV of the mitochondrial respiratory chain and creatine kinase (CK) in brain regions involved with MDD. After a single dose or serial injections over 14 days of quetiapine (20, 40, and 80 mg) were administered, isolates from the pre- frontal cortex, hippocampus, amygdala and nucleus accumbens were analyzed for enzyme activity levels. The enzyme activity varied according to the dose, brain region, and acute or chronic dosing protocols. In general, complexes I-III activity was increased, especially after acute administration. Acute administration also increased the activity of complex IV and CK in the amygdala while complex I was inhibited in the prefrontal cortex and nucleus accumbens. These results suggest that quetiapine produces an increase in respiratory chain complex activity, which may be underlying its efficacy against psychiatric disorders and neuronal damage.

  6. Beneficial effect of prolonged heme oxygenase 1 activation in a rat model of chronic heart failure

    PubMed Central

    Collino, Massimo; Pini, Alessandro; Mugelli, Niccolò; Mastroianni, Rosanna; Bani, Daniele; Fantozzi, Roberto; Papucci, Laura; Fazi, Marilena; Masini, Emanuela

    2013-01-01

    SUMMARY We and others have previously demonstrated that heme oxygenase 1 (HO-1) induction by acute hemin administration exerts cardioprotective effects. Here, we developed a rat model of heart failure to investigate whether a long-term induction of HO-1 by chronic hemin administration exerted protective effects. Sprague Dawley rats that underwent permanent ligation of the left coronary artery were closely monitored for survival rate analysis and sacrificed on day 28 post-operation. Administration of hemin (4 mg/kg body weight) every other day for 4 weeks induced a massive increase in HO-1 expression and activity, as shown by the increased levels of the two main metabolic products of heme degradation, bilirubin and carbon monoxide (CO). These effects were associated with significant improvement in survival and reduced the extension of myocardial damage. The ischemic hearts of the hemin-treated animals displayed reduced oxidative stress and apoptosis in comparison with the non-treated rats, as shown by the decreased levels of lipid peroxidation, free-radical-induced DNA damage, caspase-3 activity and Bax expression. Besides, chronic HO-1 activation suppressed the elevated levels of myeloperoxidase (MPO) activity, interleukin 1β (IL-1β) production and tumor necrosis factor-α (TNFα) production that were evoked by the ischemic injury, and increased the plasma level of the anti-inflammatory cytokine IL-10. Interestingly, HO-1 inhibitor zinc protoporphyrin IX (ZnPP-IX; 1 mg/kg) lowered bilirubin and CO concentrations to control values, thus abolishing all the cardioprotective effects of hemin. In conclusion, the results demonstrate that chronic HO-1 activation by prolonged administration of hemin improves survival and exerts protective effects in a rat model of myocardial ischemia by exerting a potent antioxidant activity and disrupting multiple levels of the apoptotic and inflammatory cascade. PMID:23592614

  7. Phenomenological correlates of metabolic activity in 18 patients with chronic schizophrenia

    SciTech Connect

    Volkow, N.D.; Wolf, A.P.; Van Gelder, P.; Brodie, J.D.; Overall, J.E.; Cancro, R.; Gomez-Mont, F.

    1987-02-01

    Using (11C)-deoxy-D-glucose and positron emission tomography (PET), the authors measured brain metabolism in 18 patients with chronic schizophrenia to assess which of the metabolic measures from two test conditions was more closely related to the patients' differing clinical characteristics. The two conditions were resting and activation, and an eye tracking task was used. Patients with more negative symptoms showed lower global metabolic rates and more severe hypofrontality than did the patients with fewer negative symptoms. Differences among the patients were distinguished by the task: sicker patients failed to show a metabolic activation response. These findings suggest that cerebral metabolic patterns reflect clinical characteristics of schizophrenic patients.

  8. Providing independent recreational activities to reduce stereotypic vocalizations in chronic schizophrenics.

    PubMed Central

    Wong, S E; Terranova, M D; Bowen, L; Zarate, R; Massel, H K; Liberman, R P

    1987-01-01

    We evaluated the effects of minimally supervised, independent recreational activities on stereotypic vocal behavior in two chronic schizophrenic patients. In baseline sessions, subjects were observed during unstructured free time in the psychiatric ward. In treatment sessions, therapists presented preferred recreational materials (magazines, models, and art projects), verbally prompted on-task behavior every 20 min, and, in one condition, administered contingent tokens. Independent recreational activities reduced medium-rate self-talk in one subject and high-rate mumbling in a second subject by 60%-70%. Results were the same with or without contingent tokens. Apparent self-maintaining characteristics of these vocal responses are discussed. PMID:3583965

  9. Clinical effects of deep cervical flexor muscle activation in patients with chronic neck pain.

    PubMed

    Kim, Jin Young; Kwag, Kwang Il

    2016-01-01

    [Purpose] The purpose of this study was to investigate clinical effects of deep cervical flexor (DCF) muscles exercise on pain, Neck Disability Index (NDI), and neck and shoulder postures in patients with chronic neck pain. [Subjects and Methods] Twenty-eight patients with chronic neck pain were randomly assigned into either the general strengthening exercise (GSE) group or the DCF activation group as control and experimental groups, respectively. All exercises were performed three times per week over 4 weeks. NDI and numeric rating scale (NRS) score for pain were determined and radiological assessment of neck-shoulder postures (head tilt angle [HTA], neck flexion angle [NFA], and forward shoulder angle [FSA]) was performed before (baseline), 4 weeks after, and 8 weeks after exercise in order to directly compare the exercise effects between the groups. [Results] In the DCF group, the NDI, NRS score, and neck-shoulder postures (analyzed by uisng HTA, NFA, and FSA) were significantly improved. [Conclusion] DCF activation exercise was effective to alleviate pain, recover functions, and correct forward head posture in the patients with neck pain. Hence, it might be recommended in the rehabilitation of patients with chronic neck pain.

  10. Quiescent hematopoietic stem cells are activated by IFNγ in response to chronic infection

    PubMed Central

    Baldridge, Megan T.; King, Katherine Y.; Boles, Nathan C.; Weksberg, David C.; Goodell, Margaret A.

    2010-01-01

    Summary Lymphocytes and neutrophils are rapidly depleted by systemic infection1. Progenitor cells of the hematopoietic system, such as common myeloid progenitors (CMPs) and common lymphoid progenitors (CLPs), increase the production of immune cells to restore and maintain homeostasis during chronic infection, but the contribution of hematopoietic stem cells (HSCs) to this process is largely unknown2. Using an in vivo mouse model of Mycobacterium avium infection, we show that an increased proportion of long-term repopulating HSCs (LT-HSCs) proliferate during M. avium infection, and that this response requires interferon-gamma (IFNγ) but not interferon-alpha (IFNα) signaling. Thus, the hematopoietic response to chronic bacterial infection involves the activation not only of intermediate blood progenitors but of LT-HSCs as well. IFNγ is sufficient to promote LT-HSC proliferation in vivo; furthermore, HSCs from mice deficient in IFNγ have a lower proliferative rate, indicating that baseline IFNγ tone regulates HSC activity. These findings are the first to implicate IFNγ both as a regulator of HSCs during homeostasis and under conditions of infectious stress. Our studies contribute to a deeper understanding of hematologic responses in patients with chronic infections such as HIV/AIDS or tuberculosis3-5. PMID:20535209

  11. Chronic methamphetamine exposure significantly decreases microglia activation in the arcuate nucleus.

    PubMed

    Lloyd, Steven A; Corkill, Beau; Bruster, Matthew C; Roberts, Rick L; Shanks, Ryan A

    2017-03-18

    Methamphetamine is a powerful psychostimulant drug and its use and abuse necessitates a better understanding of its neurobiobehavioral effects. The acute effects of binge dosing of methamphetamine on the neurons in the CNS are well studied. However, the long-term effects of chronic, low-dose methamphetamine are less well characterized, especially in other cell types and areas outside of the major dopamine pathways. Mice were administered 5mg/kg/day methamphetamine for ten days and brain tissue was analyzed using histochemistry and image analysis. Increased microglia activity in the striatum confirmed toxic effects of methamphetamine in this brain region using this dosing paradigm. A significant decrease in microglia activity in the arcuate nucleus of the hypothalamus was observed with no effect noted on dopamine neurons in the arcuate nucleus. Given the importance of this area in homeostatic and neuroendocrine regulation, the current study highlights the need to more fully understand the systemic effects of chronic, low-dose methamphetamine use. The novel finding of microglia downregulation after chronic methamphetamine could lead to advances in understanding neuroinflammatory responses towards addiction treatment and protection from psychostimulant-induced neurotoxicity.

  12. Clinical effects of deep cervical flexor muscle activation in patients with chronic neck pain

    PubMed Central

    Kim, Jin Young; Kwag, Kwang Il

    2016-01-01

    [Purpose] The purpose of this study was to investigate clinical effects of deep cervical flexor (DCF) muscles exercise on pain, Neck Disability Index (NDI), and neck and shoulder postures in patients with chronic neck pain. [Subjects and Methods] Twenty-eight patients with chronic neck pain were randomly assigned into either the general strengthening exercise (GSE) group or the DCF activation group as control and experimental groups, respectively. All exercises were performed three times per week over 4 weeks. NDI and numeric rating scale (NRS) score for pain were determined and radiological assessment of neck-shoulder postures (head tilt angle [HTA], neck flexion angle [NFA], and forward shoulder angle [FSA]) was performed before (baseline), 4 weeks after, and 8 weeks after exercise in order to directly compare the exercise effects between the groups. [Results] In the DCF group, the NDI, NRS score, and neck-shoulder postures (analyzed by uisng HTA, NFA, and FSA) were significantly improved. [Conclusion] DCF activation exercise was effective to alleviate pain, recover functions, and correct forward head posture in the patients with neck pain. Hence, it might be recommended in the rehabilitation of patients with chronic neck pain. PMID:26957772

  13. Granulocyte Macrophage Colony-Stimulating Factor-Activated Eosinophils Promote Interleukin-23 Driven Chronic Colitis.

    PubMed

    Griseri, Thibault; Arnold, Isabelle C; Pearson, Claire; Krausgruber, Thomas; Schiering, Chris; Franchini, Fanny; Schulthess, Julie; McKenzie, Brent S; Crocker, Paul R; Powrie, Fiona

    2015-07-21

    The role of intestinal eosinophils in immune homeostasis is enigmatic and the molecular signals that drive them from protective to tissue damaging are unknown. Most commonly associated with Th2 cell-mediated diseases, we describe a role for eosinophils as crucial effectors of the interleukin-23 (IL-23)-granulocyte macrophage colony-stimulating factor (GM-CSF) axis in colitis. Chronic intestinal inflammation was characterized by increased bone marrow eosinopoiesis and accumulation of activated intestinal eosinophils. IL-5 blockade or eosinophil depletion ameliorated colitis, implicating eosinophils in disease pathogenesis. GM-CSF was a potent activator of eosinophil effector functions and intestinal accumulation, and GM-CSF blockade inhibited chronic colitis. By contrast neutrophil accumulation was GM-CSF independent and dispensable for colitis. In addition to TNF secretion, release of eosinophil peroxidase promoted colitis identifying direct tissue-toxic mechanisms. Thus, eosinophils are key perpetrators of chronic inflammation and tissue damage in IL-23-mediated immune diseases and it suggests the GM-CSF-eosinophil axis as an attractive therapeutic target.

  14. Mouse running activity is lowered by Brucella abortus treatment: a potential model to study chronic fatigue.

    PubMed

    Ottenweller, J E; Natelson, B H; Gause, W C; Carroll, K K; Beldowicz, D; Zhou, X D; LaManca, J J

    1998-03-01

    Chronic fatigue syndrome, which can occur after acute infection and last for years, is characterized by severe and persistent fatigue. Others have reported decreases in mouse running activity following infection and have suggested this may provide an animal model for studying chronic fatigue. Voluntary running is a highly motivated activity in mice, which will often run 5-7 mi/day in our laboratory. Following 2 weeks of acclimation to running wheels with food and water available ad lib, female BALB/c mice received 0.2-mL tail vein injections of killed Brucella abortus (BA) or saline vehicle. Subsequently the effects on voluntary running and grooming behavior were determined. Injection of BA caused an immediate large decrease in running and a lack of grooming. Vehicle injections produced no changes in behavior. After the first several days of reduced running behavior, levels of running and grooming slowly returned back to normal over the next 2-4 weeks, with substantial individual differences in the rate of recovery. The pattern of running during recovery was intriguing in that BA mice first ran at normal levels just after the lights went out, but they stopped after only 1-2 h. As recovery proceeded, they gradually increased the duration of the running bout during the night. Because this model uses voluntary exertion and the ability to run for longer periods of time characterizes recovery, the model may be a good one for studying the biologic underpinnings of chronic fatigue.

  15. Improved cognitive, affective and anxiety measures in patients with chronic systemic disorders following structured physical activity.

    PubMed

    Teixeira, Robson Bonoto; Marins, João Carlos Bouzas; de Sá Junior, Antonio Reis; de Carvalho, Cristiane Junqueira; da Silva Moura, Tiago Augusto; Lade, Carlos Gabriel; Rizvanov, Albert A; Kiyasov, Andrey P; Mukhamedyarov, Marat A; Zefirov, Andrey L; Palotás, András; Lima, Luciana Moreira

    2015-11-01

    Mental illnesses are frequent co-morbid conditions in chronic systemic diseases. High incidences of depression, anxiety and cognitive impairment complicate cardiovascular and metabolic disorders such as hypertension and diabetes mellitus. Lifestyle changes including regular exercise have been advocated to reduce blood pressure and improve glycaemic control. The purpose of this project was to evaluate the effect of physical training on the most prevalent corollary psychiatric problems in patients with chronic organic ailments. This longitudinal study assessed the mental health of hypertensive (age: 57 ± 8 years) and/or diabetic (age: 53 ± 8 years) patients using mini-mental state examination, Beck's depression inventory, Beck's anxiety inventory and self-reporting questionnaire-20 before and after a 3-month supervised resistance and aerobic exercise programme comprising structured physical activity three times a week. Clinically relevant improvement was observed in the Beck's depression inventory and Beck's anxiety inventory scores following the 12-week training (61%, p = 0.001, and 53%, p = 0.02, respectively). Even though statistically not significant (p = 0.398), the cognitive performance of this relatively young patient population also benefited from the programme. These results demonstrate positive effects of active lifestyle on non-psychotic mental disorders in patients with chronic systemic diseases, recommending exercise as an alternative treatment option.

  16. Change in trunk muscle activities with prone bridge exercise in patients with chronic low back pain

    PubMed Central

    Kong, Yong-soo; Park, Seol; Kweon, Mi-Gyong; Park, Ji-won

    2016-01-01

    [Purpose] The aim of this study was to determine the effect of three different bridge exercises on internal oblique, external oblique, transverse abdominis, and erector spinae activities. [Subjects and Methods] Forty-five subjects with chronic low back pain participated in this study. The training outcome was evaluated with three different testing methods: supine bridge exercise, supine bridge on Swiss ball exercise, and prone bridge exercise. The activities of the transverse abdominis, internal oblique, external oblique, and erector spinae were measured using surface electromyography. [Results] There were significant differences in the internal oblique, external oblique, and erector spinae according to the three kinds of bridging exercises. The internal oblique, external oblique and transverse abdominis activities were highest in the prone bridge exercise, followed by those in the supine bridge on Swiss ball exercise, and supine bridge exercises. The activity of erector spine was highest in the supine bridge on Swiss ball exercise followed by the supine bridge exercise and prone bridge exercise. [Conclusion] These results suggest that prone bridge exercise is more effective than conventional supine bridge exercise and supine bridge on Swiss ball in increasing trunk muscle activity of chronic low back pain patients. PMID:26957771

  17. Changes in muscle activation after reach training with gravity compensation in chronic stroke patients.

    PubMed

    Prange, Gerdienke B; Krabben, Thijs; Renzenbrink, Gerbert J; Ijzerman, Maarten J; Hermens, Hermie J; Jannink, Michiel J A

    2012-09-01

    The objective of this study is to examine the effect of gravity compensation training on reaching and underlying changes in muscle activation. In this clinical trial, eight chronic stroke patients with limited arm function received 18 sessions (30 min) of gravity-compensated reach training (during 6 weeks) in combination with a rehabilitation game. Before and after training, unsupported reach (assessing maximal distance, joint angles and muscle activity of eight shoulder and elbow muscles) and the Fugl-Meyer assessment were compared. After training, the maximal reach distance improved significantly by 3.5% of arm length, together with increased elbow extension (+9.2°) and increased elbow extensor activity (+68%). In some patients, a reduced cocontraction of biceps and anterior deltoid was also involved, although this was not significant on group level. Improvements in unsupported reach after gravity compensation training in chronic stroke patients with mild to severe hemiparesis were mainly accompanied by increased activation of prime movers at the elbow, although in some patients, improved selective joint control may also have been involved. Gravity compensation seems to be a suitable way to provide active, task-specific treatment, without the need for high-tech devices. Further research on a larger scale, including control groups and combinations of arm support with functional hand training, is essential to enhance the potential of arm support to complement poststroke arm rehabilitation.

  18. Physical activity: benefit or weakness in metabolic adaptations in a mouse model of chronic food restriction?

    PubMed

    Méquinion, Mathieu; Caron, Emilie; Zgheib, Sara; Stievenard, Aliçia; Zizzari, Philippe; Tolle, Virginie; Cortet, Bernard; Lucas, Stéphanie; Prévot, Vincent; Chauveau, Christophe; Viltart, Odile

    2015-02-01

    In restrictive-type anorexia nervosa (AN) patients, physical activity is usually associated with food restriction, but its physiological consequences remain poorly characterized. In female mice, we evaluated the impact of voluntary physical activity with/without chronic food restriction on metabolic and endocrine parameters that might contribute to AN. In this protocol, FRW mice (i.e., food restriction with running wheel) reached a crucial point of body weight loss (especially fat mass) faster than FR mice (i.e., food restriction only). However, in contrast to FR mice, their body weight stabilized, demonstrating a protective effect of a moderate, regular physical activity. Exercise delayed meal initiation and duration. FRW mice displayed food anticipatory activity compared with FR mice, which was strongly diminished with the prolongation of the protocol. The long-term nature of the protocol enabled assessment of bone parameters similar to those observed in AN patients. Both restricted groups adapted their energy metabolism differentially in the short and long term, with less fat oxidation in FRW mice and a preferential use of glucose to compensate for the chronic energy imbalance. Finally, like restrictive AN patients, FRW mice exhibited low leptin levels, high plasma concentrations of corticosterone and ghrelin, and a disruption of the estrous cycle. In conclusion, our model suggests that physical activity has beneficial effects on the adaptation to the severe condition of food restriction despite the absence of any protective effect on lean and bone mass.

  19. Cooperation of imipramine blue and tyrosine kinase blockade demonstrates activity against chronic myeloid leukemia

    PubMed Central

    Laidlaw, Kamilla M.E.; Berhan, Samuel; Liu, Suhu; Silvestri, Giovannino; Holyoake, Tessa L.; Frank, David A.; Aggarwal, Bharat; Bonner, Michael Y.; Perrotti, Danilo

    2016-01-01

    The use of tyrosine kinase inhibitors (TKI), including nilotinib, has revolutionized the treatment of chronic myeloid leukemia (CML). However current unmet clinical needs include combating activation of additional survival signaling pathways in persistent leukemia stem cells after long-term TKI therapy. A ubiquitous signaling alteration in cancer, including CML, is activation of reactive oxygen species (ROS) signaling, which may potentiate stem cell activity and mediate resistance to both conventional chemotherapy and targeted inhibitors. We have developed a novel nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, imipramine blue (IB) that targets ROS generation. ROS levels are known to be elevated in CML with respect to normal hematopoietic stem/progenitor cells and not corrected by TKI. We demonstrate that IB has additive benefit with nilotinib in inhibiting proliferation, viability, and clonogenic function of TKI-insensitive quiescent CD34+ CML chronic phase (CP) cells while normal CD34+ cells retained their clonogenic capacity in response to this combination therapy in vitro. Mechanistically, the pro-apoptotic activity of IB likely resides in part through its dual ability to block NF-κB and re-activate the tumor suppressor protein phosphatase 2A (PP2A). Combining BCR-ABL1 kinase inhibition with NADPH oxidase blockade may be beneficial in eradication of CML and worthy of further investigation. PMID:27438151

  20. The inhibition of matrix metalloproteinase activity in chronic wounds by a polyacrylate superabsorber.

    PubMed

    Eming, Sabine; Smola, Hans; Hartmann, Berenike; Malchau, Gebhart; Wegner, Ronny; Krieg, Thomas; Smola-Hess, Sigrun

    2008-07-01

    Excessive matrix metalloproteinase (MMP) levels have been observed in wound fluid of impaired healing wounds. This is thought to interfere with granulation tissue formation as newly formed extracellular matrix and cytokines are degraded and the wound becomes deadlocked, unable to progress to the next healing stages. In the cleansing phase, associated with high MMP activity levels, hydroactive wound dressings containing polyacrylate superabsorber particles are particularly effective. We tested whether these particles can block MMP activity in wound fluid obtained from chronic venous leg ulcers. Polyacrylate superabsorber particles inhibited MMP activity by more than 87% in a fluorogenic peptide substrate assay. Further analysis revealed two underlying molecular mechanisms. First, experiments showed direct binding of MMPs to the particles. Secondly, polyacrylate superabsorber particles can bind Ca2+ and Zn2+ ions competing with MMPs for divalent ions required for enzymatic activity. Furthermore, we provide the first evidence in vivo that MMPs bind effectively to polyacrylate superabsorber particles within the hostile environment of chronic wounds. We conclude that polyacrylate superabsorber particles can rescue the highly proteolytic microenvironment of non-healing wounds from MMP activity so that more conductive conditions allow healing to proceed.

  1. Palmitoylethanolamide inhibits rMCP-5 expression by regulating MITF activation in rat chronic granulomatous inflammation.

    PubMed

    De Filippis, Daniele; Russo, Annapina; De Stefano, Daniela; Cipriano, Mariateresa; Esposito, Davide; Grassia, Gianluca; Carnuccio, Rosa; Russo, Giulia; Iuvone, Teresa

    2014-02-15

    Chronic inflammation, a condition frequently associated with several pathologies, is characterized by angiogenic and fibrogenic responses that may account for the development of granulomatous tissue. We previously demonstrated that the chymase, rat mast cell protease-5 (rMCP-5), exhibits pro-inflammatory and pro-angiogenic properties in a model of chronic inflammation sustained by mast cells (MCs), granuloma induced by the subcutaneous carrageenan-soaked sponge implant in rat. In this study, we investigated the effects of palmitoylethanolamide (PEA), an anti-inflammatory and analgesic endogenous compound, on rMCP-5 mRNA expression and Microphtalmia-associated Transcription Factor (MITF) activation in the same model of chronic inflammation. The levels of rMCP-5 mRNA were detected using semi-quantitative RT-PCR; the protein expression of chymase and extracellular signal-regulated kinases (ERK) were analyzed by western blot; MITF/DNA binding activity and MITF phosphorylation were assessed by electrophoretic mobility shift assay (EMSA) and immunoprecipitation, respectively. The administration of PEA (200, 400 and 800 µg/ml) significantly decreased rMCP-5 mRNA and chymase protein expression induced by λ-carrageenan. These effects were associated with a significant decrease of MITF/DNA binding activity and phosphorylated MITF as well as phosphorylated ERK levels. In conclusion, our results, showing the ability of PEA to inhibit MITF activation and chymase expression in granulomatous tissue, may yield new insights into the understanding of the signaling pathways leading to MITF activation controlled by PEA.

  2. Brain activation of lower extremity movement in chronically impaired stroke survivors.

    PubMed

    Luft, Andreas R; Forrester, Larry; Macko, Richard F; McCombe-Waller, Sandy; Whitall, Jill; Villagra, Federico; Hanley, Daniel F

    2005-05-15

    Lower extremity paresis poses significant disability to chronic stroke survivors. Unlike for the upper extremity, cortical adaptations in networks controlling the paretic leg have not been characterized after stroke. Here, the hypotheses are that brain activation associated with unilateral knee movement in chronic stroke survivors is abnormal, depends on lesion location, and is related to walking ability. Functional magnetic resonance imaging of unilateral knee movement was obtained in 31 patients 26.9 months (mean, IQ range: 11.3-68.1) after stroke and in 10 age-matched healthy controls. Strokes were stratified according to lesion location. Locomotor disability (30 ft walking speed) did not differ between patient groups (9 cortical, 12 subcortical, 10 brainstem lesions). Significant differences in brain activation as measured by voxel counts in 10 regions of interest were found between controls and patients with brainstem (P = 0.006) and cortical strokes (P = 0.002), and between subcortical and cortical patients (P = 0.026). Statistical parametric mapping of data per group revealed similar activation patterns in subcortical patients and controls with recruitment of contralateral primary motor cortex (M1), supplementary motor area (SMA), and bilateral somatosensory area 2 (S2). Cortical recruitment was reduced in brainstem and cortical stroke. Better walking was associated with lesser contralateral sensorimotor cortex activation in brainstem, but stronger recruitment of ipsilateral sensorimotor and bilateral somatosensory cortices in subcortical and cortical patients, respectively. A post hoc comparison of brainstem patients with and without mirror movements (50%) revealed lesser recruitment of ipsilateral cerebellum in the latter. Subcortical patients with mirror movements (58%) showed lesser bilateral sensorimotor cortex activation. No cortical patient had mirror movements. The data reveal adaptations in networks controlling unilateral paretic knee movement in

  3. [Activating physiotherapy for chronic pain in elderly patients. Recommendations, barriers and resources].

    PubMed

    Kuss, K; Laekeman, M

    2015-08-01

    Elderly patients with chronic pain are particularly at risk of functional limitations up to the loss of autonomy and social life. To facilitate autonomy, mobility and quality of life, physiotherapy plays an essential role in pain management. Nevertheless, programs that are specifically geared towards the needs of older patients are still uncommon. This article offers recommendations for structuring physiotherapy programs based on international guideline recommendations. First examples of pain management concepts for older adults demonstrate the positive results of activating therapy. Additionally, this article provides insights into barriers and resources of affected patients and all actors involved. However, physiotherapeutic treatment for aged chronic pain patients in Germany still shows considerable shortcomings but also offers an exciting challenge for the future.

  4. Immunopathogenesis of granulomas in chronic autoinflammatory diseases

    PubMed Central

    Timmermans, Wilhelmina Maria Cornelia; van Laar, Jan Alexander Michael; van Hagen, Petrus Martinus; van Zelm, Menno Cornelis

    2016-01-01

    Granulomas are clusters of immune cells. These structures can be formed in reaction to infection and display signs of necrosis, such as in tuberculosis. Alternatively, in several immune disorders, such as sarcoidosis, Crohn's disease and common variable immunodeficiency, non-caseating granulomas are formed without an obvious infectious trigger. Despite advances in our understanding of the human immune system, the pathogenesis underlying these non-caseating granulomas in chronic inflammatory diseases is still poorly understood. Here, we review the current knowledge about the immunopathogenesis of granulomas, and we discuss how the involved immune cells can be targeted with novel therapeutics. PMID:28090320

  5. Blood myeloid and lymphoid dendritic cells reflect Th1/Th2 balance in sarcoidosis and extrinsic allergic alveolitis.

    PubMed

    Buczkowski, Jarosław; Krawczyk, Paweł; Chocholska, Sylwia; Tabarkiewicz, Jacek; Kieszko, Robert; Michnar, Marek; Milanowski, Janusz; Roliński, Jacek

    2003-01-01

    Dendritic cells play a specific regulatory role in the immune system. In this paper, the significance of myeloid and lymphoid dendritic cells in sarcoidosis and extrinsic allergic alveolitis (EAA) was evaluated. Myeloid dendritic cells are connected with Th1 type of immunological response, whereas lymphoid ones--with Th2 type. The latest findings indicate that both diseases are characterized by serious disturbances of Th1/Th2 response to Th1 dominance. Our studies seem to confirm these suggestions. In the peripheral blood of patients with sarcoidosis as well as with EAA, myeloid dendritic cells outnumbered lymphoid ones.

  6. Early chronic lead exposure reduces exploratory activity in young C57BL/6J mice.

    PubMed

    Flores-Montoya, Mayra Gisel; Sobin, Christina

    2015-07-01

    Research has suggested that chronic low-level lead exposure diminishes neurocognitive function in children. Tests that are sensitive to behavioral effects at lowest levels of lead exposure are needed for the development of animal models. In this study we investigated the effects of chronic low-level lead exposure on exploratory activity (unbaited nose poke task), exploratory ambulation (open field task) and motor coordination (Rotarod task) in pre-adolescent mice. C57BL/6J pups were exposed to 0 ppm (controls), 30 ppm (low-dose) or 230 ppm (high-dose) lead acetate via dams' drinking water administered from birth to postnatal day 28, to achieve a range of blood lead levels (BLLs) from not detectable to 14.84 µg dl(-1) ). At postnatal day 28, mice completed behavioral testing and were killed (n = 61). BLLs were determined by inductively coupled plasma mass spectrometry. The effects of lead exposure on behavior were tested using generalized linear mixed model analyses with BLL, sex and the interaction as fixed effects, and litter as the random effect. BLL predicted decreased exploratory activity and no threshold of effect was apparent. As BLL increased, nose pokes decreased. The C57BL/6J mouse is a useful model for examining effects of early chronic low-level lead exposure on behavior. In the C57BL/6J mouse, the unbaited nose poke task is sensitive to the effects of early chronic low-level lead exposure. This is the first animal study to show behavioral effects in pre-adolescent lead-exposed mice with BLL below 5 µg dl(-1).

  7. Different adaptation of the motor activity rhythm to chronic phase shifts between adolescent and adult rats.

    PubMed

    Albert, Nerea; da Silva, Crhistiane; Díez-Noguera, Antoni; Cambras, Trinitat

    2013-09-01

    Chronic phase shifts is a common feature in modern societies, which may induce sleep alterations and other health problems. The effects of phase shift on the circadian rhythms have been described to be more pronounced in old than in young animals. However, few works address the effects of chronic phase shifts during adolescence. Here we tested the development of the motor activity circadian rhythm of young rats under chronic phase shifts, which consisted on 6-h advances (A), 6h delays (D) or 6h advances and delays alternated every 5 days (AD) during the first 60 days after weaning. Moreover, the rhythmic pattern was compared to that of adult rats under the same lighting conditions. Results indicate that adolescent rats, independently on the lighting environment, developed a clear circadian rhythm, whose amplitude increased the first 50 days after weaning and showed a more stable circadian rhythm than adults under the same lighting conditions. In the case of A and AD groups, circadian disruption was observed only in adult rats. In all groups, the offset of activity correlated with light pattern better than the onset, and this correlation was always higher in the case of the rhythm of the pubertal rats. When AD groups were transferred to constant darkness, the group submitted to this condition during adolescence showed shorter period than that submitted in their adulthood. In conclusion, differently from adult rats, adolescent rats submitted to chronic phase shifts did not show circadian disruption and developed a single circadian rhythm, suggesting permanent changes in the circadian system.

  8. Cardiopulmonary exercise testing variables as predictors of long-term outcome in thoracic sarcoidosis

    PubMed Central

    Lopes, A.J.; Menezes, S.L.S.; Dias, C.M.; Oliveira, J.F.; Mainenti, M.R.M.; Guimarães, F.S.

    2012-01-01

    Cardiopulmonary exercise testing (CPET) plays an important role in the assessment of functional capacity in patients with interstitial lung disease. The aim of this study was to identify CPET measures that might be helpful in predicting the vital capacity and diffusion capacity outcomes of patients with thoracic sarcoidosis. A longitudinal study was conducted on 42 nonsmoking patients with thoracic sarcoidosis (median age = 46.5 years, 22 females). At the first evaluation, spirometry, the measurement of single-breath carbon monoxide diffusing capacity (DLCOsb) and CPET were performed. Five years later, the patients underwent a second evaluation consisting of spirometry and DLCOsb measurement. After 5 years, forced vital capacity (FVC)% and DLCOsb% had decreased significantly [95.5 (82-105) vs 87.5 (58-103) and 93.5 (79-103) vs 84.5 (44-102), respectively; P < 0.0001 for both]. In CPET, the peak oxygen uptake, maximum respiratory rate, breathing reserve, alveolar-arterial oxygen pressure gradient at peak exercise (P(A-a)O2), and Δ SpO2 values showed a strong correlation with the relative differences for FVC% and DLCOsb% (P < 0.0001 for all). P(A-a)O2 ≥22 mmHg and breathing reserve ≤40% were identified as significant independent variables for the decline in pulmonary function. Patients with thoracic sarcoidosis showed a significant reduction in FVC% and DLCOsb% after 5 years of follow-up. These data show that the outcome measures of CPET are predictors of the decline of pulmonary function. PMID:22331135

  9. Endosonography‑guided fine‑needle aspiration in the diagnosis of sarcoidosis: a randomized study.

    PubMed

    Kocoń, Piotr; Szlubowski, Artur; Kużdżał, Jarosław; Rudnicka-Sosin, Lucyna; Ćmiel, Adam; Soja, Jerzy; Włodarczyk, Janusz R; Talar, Piotr; Smęder, Tomasz; Gil, Tomasz; Warmus, Janusz; Tomaszewska, Romana

    2017-03-31

    INTRODUCTION    There are no widely accepted standards for the diagnosis of sarcoidosis. OBJECTIVES    The aim of this study was to assess the relative diagnostic yield of endobronchial ultrasound fine-needle aspiration (EBUS -FNA) and endoscopic ultrasound fine needle aspiration (EUS -FNA), and to compare them with standard diagnostic techniques such as endobronchial biopsy (EBB), transbronchial lung biopsy (TBLB), transbronchial needle aspiration (TBNA), and mediastinoscopy. PATIENTS AND METHODS    This was a prospective randomized study including consecutive patients with clinical diagnosis of stage I or II sarcoidosis. EBB, TBLB, and TBNA were performed at baseline in all patients. Subsequently, patients were randomized to group A (EBUS -FNA) or group B (EUS -FNA). Next, a crossover control test was performed: all patients with negative results in group A underwent EUS -FNA and all patients with negative results in group B underwent EBUS -FNA. If sarcoidosis was not confirmed, mediastinoscopy was performed. RESULTS    We enrolled 106 patients, of whom 100 were available for the final analysis. The overall sensitivity and accuracy of standard endoscopic methods were 64% each. When analyzing each of the standard endoscopic methods separately, the diagnosis was confirmed with EBB in 12 patients (12%), with TBLB in 42 patients (42%), and with TBNA in 44 patients (44%). The sensitivity and accuracy of each endosonographic technique were significantly higher than those of EBB+TBLB+TBNA (P = 0.0112 vs P = 0.0134). CONCLUSIONS    The sensitivity and accuracy of EBUS -FNA and EUS -FNA are significantly higher than those of standard endoscopic methods. Moreover, the sensitivity and accuracy of EUS -FNA tend to be higher than those of EBUS -FNA.

  10. Digestive-tract sarcoidosis: French nationwide case-control study of 25 cases.

    PubMed

    Ghrenassia, Etienne; Mekinian, Arsene; Chapelon-Albric, Catherine; Levy, Pierre; Cosnes, Jacques; Sève, Pascal; Lefèvre, Guillaume; Dhôte, Robin; Launay, David; Prendki, Virginie; Morell-Dubois, Sandrine; Sadoun, Danielle; Mehdaoui, Anas; Soussan, Michael; Bourrier, Anne; Ricard, Laure; Benamouzig, Robert; Valeyre, Dominique; Fain, Olivier

    2016-07-01

    Digestive tract sarcoidosis (DTS) is rare and case-series are lacking. In this retrospective case-control study, we aimed to compare the characteristics, outcome, and treatment of patients with DTS, nondigestive tract sarcoidosis (NDTS), and Crohn disease.We included cases of confirmed sarcoidosis, symptomatic digestive tract involvement, and noncaseating granuloma in any digestive tract. Each case was compared with 2 controls with sarcoidoisis without digestive tract involvement and 4 with Crohn disease.We compared 25 cases of DTS to 50 controls with NDTS and 100 controls with Crohn disease. The major digestive clinical features were abdominal pain (56%), weight loss (52%), nausea/vomiting (48%), diarrhea (32%), and digestive bleeding (28%). On endoscopy of DTS, macroscopic lesions were observed in the esophagus (9%), stomach (78%), duodenum (9%), colon, (25%) and rectum (19%). As compared with NDTS, DTS was associated with weight loss (odds ratio [OR] 5.8; 95% confidence interval [CI] 1.44-23.3) and the absence of thoracic adenopathy (OR 5.0; 95% CI 1.03-25). As compared with Crohn disease, DTS was associated with Afro-Caribbean origin (OR 27; 95% CI 3.6-204) and the absence of ileum or colon macroscopic lesions (OR 62.5; 95% CI 10.3-500). On the last follow-up, patients with DTS showed no need for surgery (versus 31% for patients with Crohn disease; P = 0.0013), and clinical digestive remission was frequent (76% vs. 35% for patients with Crohn disease; P = 0.0002).The differential diagnosis with Crohn disease could be an issue with DTS. Nevertheless, the 2 diseases often have different clinical presentation and outcome.

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

    PubMed

    Dalgleish, Angus G; O'Byrne, Ken J

    2002-01-01

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

  12. Inhibiting autophagy potentiates the anticancer activity of IFN1@/IFNα in chronic myeloid leukemia cells.

    PubMed

    Zhu, Shan; Cao, Lizhi; Yu, Yan; Yang, Liangchun; Yang, Minghua; Liu, Ke; Huang, Jun; Kang, Rui; Livesey, Kristen M; Tang, Daolin

    2013-03-01

    IFN1@ (interferon, type 1, cluster, also called IFNα) has been extensively studied as a treatment for patients with chronic myeloid leukemia (CML). The mechanism of anticancer activity of IFN1@ is complex and not well understood. Here, we demonstrate that autophagy, a mechanism of cellular homeostasis for the removal of dysfunctional organelles and proteins, regulates IFN1@-mediated cell death. IFN1@ activated the cellular autophagic machinery in immortalized or primary CML cells. Activation of JAK1-STAT1 and RELA signaling were required for IFN1@-induced expression of BECN1, a key regulator of autophagy. Moreover, pharmacological and genetic inhibition of autophagy enhanced IFN1@-induced apoptosis by activation of the CASP8-BID pathway. Taken together, these findings provide evidence for an important mechanism that links autophagy to immunotherapy in leukemia.

  13. Chronic enhancement of CREB activity in the hippocampus interferes with the retrieval of spatial information

    PubMed Central

    Viosca, Jose; Malleret, Gaël; Bourtchouladze, Rusiko; Benito, Eva; Vronskava, Svetlana; Kandel, Eric R.; Barco, Angel

    2009-01-01

    The activation of cAMP-responsive element-binding protein (CREB)-dependent gene expression is thought to be critical for the formation of different types of long-term memory. To explore the consequences of chronic enhancement of CREB function on spatial memory in mammals, we examined spatial navigation in bitransgenic mice that express in a regulated and restricted manner a constitutively active form of CREB, VP16-CREB, in forebrain neurons. We found that chronic enhancement of CREB activity delayed the acquisition of an allocentric strategy to solve the hidden platform task. The ability to turn on and off transgene expression allowed us to dissect the role of CREB in dissociable memory processes. In mice in which transgene expression was turned on during memory acquisition, turning off the transgene re-established the access to the memory trace, whereas in mice in which transgene expression was turned off during acquisition, turning on the transgene impaired memory expression in a reversible manner, indicating that CREB enhancement specifically interfered with the retrieval of spatial information. The defects on spatial navigation in mice with chronic enhancement of CREB function were not corrected by conditions that increased further CREB-dependent activation of hippocampal memory systems, such as housing in an enriched environment. These results along with previous findings in CREB-deficient mutants indicate that the relationship of CREB-mediated plasticity to spatial memory is an inverted-U function, and that optimal learning in the water maze requires accurate regulation of this pathway. PMID:19237642

  14. Resolution of Cutaneous Sarcoidosis Following Topical Application of Ganoderma lucidum (Reishi Mushroom).

    PubMed

    Saylam Kurtipek, Gulcan; Ataseven, Arzu; Kurtipek, Ercan; Kucukosmanoglu, İlknur; Toksoz, Mustafa Rasid

    2016-03-01

    Ganoderma lucidum (reishi mushroom) has been used in traditional Chinese and Japanese medicine as a herbal remedy for over 2000 years. Studies have shown that G. lucidum has anti-allergic, anti-oxidant, anti-tumor, anti-viral, and anti-inflammatory properties. A review of the literature revealed that there were no studies examining the use of G. lucidum for the treatment of skin diseases. Here, we report the case of a 44-year-old male patient who used soap enriched with G. lucidum and goat's milk for 3 days in treating annular cutaneous sarcoidosis. The patient showed almost complete regression of the lesions.

  15. Right Ventricular Cardiomyopathy Meeting the Arrhythmogenic Right Ventricular Dysplasia Revised Criteria? Don't Forget Sarcoidosis!

    PubMed Central

    Vasaturo, Sabina; Ploeg, David E.; Buitrago, Guadalupe; Zeppenfeld, Katja; Veselic-Charvat, Maud

    2015-01-01

    A 53-year-old woman was referred for ventricular fibrillation with resuscitation. A CT-angiography showed signs of a right ventricular enlargement without obvious cause. A cardiac MRI demonstrated a dilated and hypokinetic right ventricle with extensive late gadolinium enhancement. Arrhythmogenic right ventricular dysplasia (ARVD) was suspected according to the "revised ARVD task force criteria". An endomyocardial biopsy was inconclusive. The patient developed purulent pericarditis after epicardial ablation therapy and died of toxic shock syndrome. The post-mortem pathologic examination demonstrated sarcoidosis involving the heart, lungs, and thyroid gland. PMID:25995699

  16. Clinical and molecular study of 4 cases of pulmonary hypertension associated with sarcoidosis.

    PubMed

    Baloira Villar, Adolfo; Pousada Fernández, Guillermo; Núñez Fernández, Marta; Valverde Pérez, Diana

    2015-04-01

    Sarcoidosis is a pleomorphic disease that can present with pulmonary hypertension (PH). What little information is available about the association of these two diseases comes mainly from small series of patients scheduled for transplant. We present 4 cases of mild pulmonary involvement in whom right catheterisation was performed and PH-specific therapy was administered. After obtaining written consent, a genetic study was performed that showed mutations in PH-related genes in 3 of the patients. This is the first study of its kind to yield genetic information for this type of PH.

  17. Assessment of adenosine deaminase (ADA) activity and oxidative stress in patients with chronic tonsillitis.

    PubMed

    Garca, Mehmet Fatih; Demir, Halit; Turan, Mahfuz; Bozan, Nazım; Kozan, Ahmet; Belli, Şeyda Bayel; Arslan, Ayşe; Cankaya, Hakan

    2014-06-01

    To emphasize the effectiveness of adenosine deaminase (ADA) enzyme, which has important roles in the differentiation of lymphoid cells, and oxidative stress in patients with chronic tonsillitis. Serum and tissue samples were obtained from 25 patients who underwent tonsillectomy due to recurrent episodes of acute tonsillitis. In the control group, which also had 25 subjects, only serum samples were taken as obtaining tissue samples would not have been ethically appropriate. ADA enzyme activity, catalase (CAT), carbonic anhydrase (CA), nitric oxide (NO) and malondialdehyde (MDA) were measured in the serum and tissue samples of patients and control group subjects. The serum values of both groups were compared. In addition, the tissue and serum values of patients were compared. Serum ADA activity and the oxidant enzymes MDA and NO values of the patient group were significantly higher than those of the control group (p < 0.001), the antioxidant enzymes CA and CAT values of the patient group were significantly lower than those of the control group (p < 0.001). In addition, while CA, CAT and NO enzyme levels were found to be significantly higher in the tonsil tissue of the patient group when compared to serum levels (p < 0.05), there was no difference between tissue and serum MDA and ADA activity (p > 0.05). Elevated ADA activity may be effective in the pathogenesis of chronic tonsillitis both by impairing tissue structure and contributing to SOR formation.

  18. Effects of active chronic cocaine use on cardiac sympathetic neuronal function assessed by carbon-11-hydroxyephedrine

    SciTech Connect

    Melon, P.G.; Boyd, C.J.; McVey, S. |

    1997-03-01

    Cardiac toxicity of cocaine has been linked to its inhibitory effect on norepinephrine reuptake by sympathetic nerve terminals of the heart. Carbon-11-hydroxyephedrine is a positron-emitting tracer that has been validated as a highly specific marker for norepinephrine transporter activity of the sympathetic nerve terminals and thus makes possible in vivo assessment of the effect of cocaine on norepinephrine reuptake and storage in the cardiac sympathetic nerve terminals. The aim of the study was to use the catecholamine analog {sup 11}C-hydroxyephedrine with PET to determine whether active chronic use of cocaine in women modifies the function of sympathetic nerve terminals of the heart. Six normal female volunteers and nine female active chronic cocaine users were studied. Cardiac regional {sup 11}C-hydroxyephedrine uptake and blood flow, as assessed with {sup 13}N-ammonia, were determined using semi-quantitative polar map analysis of myocardial tracer distribution. Carbon-11-hydroxyephedrine cardiac retention was quantified using dynamic data acquisition and kinetic analysis of blood and tissue activity. 27 refs., 4 figs., 3 tabs.

  19. Neutrophil activity in chronic venous leg ulcers—A target for therapy?

    PubMed Central

    McDaniel, Jodi C.; Roy, Sashwati; Wilgus, Traci A.

    2013-01-01

    Chronic venous leg ulcers (CVLUs) affect approximately 600,000 people annually in the United States and accrue yearly treatment costs of US$2.5–5 billion. As the population ages, demands on health care resources for CVLU treatments are predicted to drastically increase because the incidence of CVLUs is highest in those ≥65 years of age. Furthermore, regardless of current standards of care, healing complications and high recurrence rates prevail. Thus, it is critical that factors leading to or exacerbating CVLUs be discerned and more effective, adjuvant, evidence-based treatment strategies be utilized. Previous studies have suggested that CVLUs’ pathogenesis is related to the prolonged presence of high numbers of activated neutrophils secreting proteases in the wound bed that destroy growth factors, receptors, and the extracellular matrix that are essential for healing. These events are believed to contribute to a chronically inflamed wound that fails to heal. Therefore, the purpose of this project was to review studies from the past 15 years (1996–2011) that characterized neutrophil activity in the microenvironment of human CVLUs for new evidence that could explicate the proposed relationship between excessive, sustained neutrophil activity and CVLUs. We also appraised the strength of evidence for current and potential therapeutics that target excessive neutrophil activity. PMID:23551462

  20. Activation of retinal tyrosine hydroxylase: tolerance induced by chronic treatment with haloperidol does not modify response to light

    SciTech Connect

    Cohen, J.; Neff, N.H.

    1982-05-01

    A single dose of haloperidol administered to rats in the dark increases the activity of retinal tyrosine hydroxylase. The ability of haloperidol to activate the enzyme is diminished 24 hr after terminating 22 to 30 days of treatment with haloperidol. The retinal enzyme is also tolerant to activation by treatment with chlorpromazine. In contrast, exposure of the animals to light activates the enzyme to the same extent in chronic haloperidol-treated and control animals. Thus, chronic haloperidol treatment does not modify the ability of the retinal enzyme system to respond to the physiological stimulus, light. Apparently, activation of retinol tyrosine hydroxylase by haloperidol and light occurs by independent mechanisms.

  1. Protease-activated receptor 2 activation is sufficient to induce the transition to a chronic pain state.

    PubMed

    Tillu, Dipti V; Hassler, Shayne N; Burgos-Vega, Carolina C; Quinn, Tammie L; Sorge, Robert E; Dussor, Gregory; Boitano, Scott; Vagner, Josef; Price, Theodore J

    2015-05-01

    Protease-activated receptor type 2 (PAR2) is known to play an important role in inflammatory, visceral, and cancer-evoked pain based on studies using PAR2 knockout (PAR2(-/-)) mice. We have tested the hypothesis that specific activation of PAR2 is sufficient to induce a chronic pain state through extracellular signal-regulated kinase (ERK) signaling to protein synthesis machinery. We have further tested whether the maintenance of this chronic pain state involves a brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (trkB)/atypical protein kinase C (aPKC) signaling axis. We observed that intraplantar injection of the novel highly specific PAR2 agonist, 2-aminothiazol-4-yl-LIGRL-NH2 (2-at), evokes a long-lasting acute mechanical hypersensitivity (median effective dose ∼12 pmoles), facial grimacing, and causes robust hyperalgesic priming as revealed by a subsequent mechanical hypersensitivity and facial grimacing to prostaglandin E2 (PGE2) injection. The promechanical hypersensitivity effect of 2-at is completely absent in PAR2(-/-) mice as is hyperalgesic priming. Intraplantar injection of the upstream ERK inhibitor, U0126, and the eukaryotic initiation factor (eIF) 4F complex inhibitor, 4EGI-1, prevented the development of acute mechanical hypersensitivity and hyperalgesic priming after 2-at injection. Systemic injection of the trkB antagonist ANA-12 similarly inhibited PAR2-mediated mechanical hypersensitivity, grimacing, and hyperalgesic priming. Inhibition of aPKC (intrathecal delivery of ZIP) or trkB (systemic administration of ANA-12) after the resolution of 2-at-induced mechanical hypersensitivity reversed the maintenance of hyperalgesic priming. Hence, PAR2 activation is sufficient to induce neuronal plasticity leading to a chronic pain state, the maintenance of which is dependent on a BDNF/trkB/aPKC signaling axis.

  2. Natural healers: a review of animal assisted therapy and activities as complementary treatment for chronic conditions.

    PubMed

    Reed, Reiley; Ferrer, Lilian; Villegas, Natalia

    2012-01-01

    The primary objective of this review is to synthesize the existing literature on the use of animal-assisted therapy and activity (AAT/A) as complementary treatment among people living with chronic disease and to discuss the possible application of this practice among children living with HIV. Relevant databases were searched between March 10 and April 11, 2011, using the words: animal assisted therapy or treatment and chronic conditions or diseases. Thirty-one articles were found and 18 followed the inclusion and exclusion criteria. Research suggests that AAT/A is effective for different patient profiles, particularly children. Interaction with dogs has been found to increase positive behaviors, such as sensitivity and focus, in children with social disabilities. Decreased levels of pain have also been reported among child patients as a result of AAT/A. More research should be done in the area of children living with chronic diseases that require strict adherence to treatment, such as HIV, and on AAT/A's prospective use as an educational tool to teach children about the importance of self-care for their medical conditions.

  3. Effects of hypercapnia and inspiratory flow-resistive loading on respiratory activity in chronic airways obstruction.

    PubMed Central

    Altose, M D; McCauley, W C; Kelsen, S G; Cherniack, N S

    1977-01-01

    The respiratory responses to hypercapnia alone and to hypercapnia and flow-resistive loading during inspiration were studied in normal individuals and in eucapnic and hypercapnic patients with chronic airways obstruction. Responses were assessed in terms of minute ventilation and occlusion pressure (mouth pressure during airway occlusion 100 ms after the onset of inspiration). Ventilatory responses to CO2 (deltaV/deltaPCO2) were distinctly subnormal in both groups of patients with airways obstruction. The two groups of patients, however, showed different occlusion pressure responses to CO2 (deltaP100/deltaPCO2): deltaP100/deltaPCO2 was normal in the eucapnic patients but subnormal in the hypercapnic patients. Flow-resistive loading during inspiration reduced deltaV/deltaPCO2 both in normal subjects and in patients with airways obstruction. The occlusion pressure response to CO2 increased in normal subjects during flow-resistive loading but remained unchanged in both groups of patients with chronic airways obstruction. These results indicate that while chemosensitivity as determined by deltaP100/deltaPCO2 is impaired only in hypercapnic patients with chronic airways obstruction, an acute increase in flow resistance elicits a subnormal increase in respiratory efferent activity in both eucapnic and hypercapnic patients. PMID:838862

  4. Validity of activity monitors in health and chronic disease: a systematic review

    PubMed Central

    2012-01-01

    The assessment of physical activity in healthy populations and in those with chronic diseases is challenging. The aim of this systematic review was to identify whether available activity monitors (AM) have been appropriately validated for use in assessing physical activity in these groups. Following a systematic literature search we found 134 papers meeting the inclusion criteria; 40 conducted in a field setting (validation against doubly labelled water), 86 in a laboratory setting (validation against a metabolic cart, metabolic chamber) and 8 in a field and laboratory setting. Correlation coefficients between AM outcomes and energy expenditure (EE) by the criterion method (doubly labelled water and metabolic cart/chamber) and percentage mean differences between EE estimation from the monitor and EE measurement by the criterion method were extracted. Random-effects meta-analyses were performed to pool the results across studies where possible. Types of devices were compared using meta-regression analyses. Most validation studies had been performed in healthy adults (n = 118), with few carried out in patients with chronic diseases (n = 16). For total EE, correlation coefficients were statistically significantly lower in uniaxial compared to multisensor devices. For active EE, correlations were slightly but not significantly lower in uniaxial compared to triaxial and multisensor devices. Uniaxial devices tended to underestimate TEE (−12.07 (95%CI; -18.28 to −5.85) %) compared to triaxial (−6.85 (95%CI; -18.20 to 4.49) %, p = 0.37) and were statistically significantly less accurate than multisensor devices (−3.64 (95%CI; -8.97 to 1.70) %, p<0.001). TEE was underestimated during slow walking speeds in 69% of the lab validation studies compared to 37%, 30% and 37% of the studies during intermediate, fast walking speed and running, respectively. The high level of heterogeneity in the validation studies is only partly explained by the type of activity

  5. The Role of Platelet-Activating Factor in Chronic Inflammation, Immune Activation, and Comorbidities Associated with HIV Infection

    PubMed Central

    Kelesidis, Theodoros; Papakonstantinou, Vasiliki; Detopoulou, Paraskevi; Fragopoulou, Elizabeth; Chini, Maria; Lazanas, Marios C.; Antonopoulou, Smaragdi

    2016-01-01

    With the advent of highly effective antiretroviral therapy, cardiovascular disease has become an important cause of morbidity and mortality among people with treated HIV-1, but the pathogenesis is unclear. Platelet-activating factor is a potent lipid mediator of inflammation that has immunomodulatory effects and a pivotal role in the pathogenesis of inflammatory disorders and cardiovascular disease. Limited scientific evidence suggests that the platelet-activating factor pathway may be a mechanistic link between HIV-1 infection, systemic inflammation, and immune activation that contribute to pathogenesis of chronic HIV-related comorbidities, including cardiovascular disease and HIV-associated neurocognitive disorders. In this review, we examine the mechanisms by which the cross-talk between HIV-1, immune dysregulation, inflammation, and perturbations in the platelet-activating factor pathway may directly affect HIV-1 immunopathogenesis. Understanding the role of platelet-activating factor in HIV-1 infection may pave the way for further studies to explore therapeutic interventions, such as diet, that can modify platelet-activating factor activity and use of platelet-activating factor inhibitors that might improve the prognosis of HIV-1 infected patients. PMID:26616844

  6. Immune Activation Response in Chronic HIV-Infected Patients: Influence of Hepatitis C Virus Coinfection

    PubMed Central

    Márquez, Mercedes; Romero-Cores, Paula; Montes-Oca, Monserrat; Martín-Aspas, Andrés; Soto-Cárdenas, María-José; Guerrero, Francisca; Fernández-Gutiérrez, Clotilde; Girón-González, José-Antonio

    2015-01-01

    Objectives We have analyzed the parameters (bacterial translocation, immune activation and regulation, presence of HCV coinfection) which could be implicated in an inappropriate immune response from individuals with chronic HIV infection. The influence of them on the evolution of CD4+ T cell count has been investigated. Patients and methods Seventy HIV-infected patients [monoinfected by HIV (n = 20), HCV-coinfected (with (n = 25) and without (n = 25) liver cirrhosis)] and 25 healthy controls were included. Median duration of HIV infection was 20 years. HIV- and HCV-related parameters, as well as markers relative to bacterial translocation, monocyte and lymphocyte activation and regulation were considered as independent variables. Dependent variables were the increase of CD4+ T cell count during the follow-up (12 months). Results Increased values of bacterial translocation, measured by lipopolysaccharide-binding protein, monocyte and lymphocyte activation markers and T regulatory lymphocytes were detected in HIV-monoinfected and HIV/HCV coinfected patients. Serum sCD14 and IL-6 were increased in HIV/HCV-coinfected patients with liver cirrhosis in comparison with those with chronic hepatitis or HIV-monoinfected individuals. Time with undetectable HIV load was not related with these parameters. The presence of cirrhosis was negatively associated with a CD4+ T cell count increase. Conclusion In patients with a chronic HIV infection, a persistent increase of lipopolysaccharide-binding protein and monocyte and lymphocyte modifications are present. HCV-related cirrhosis is associated with more elevated serum concentrations of monocyte-derived markers. Cirrhosis influences the continued immune reconstitution of these patients. PMID:25775475

  7. Chronic activation of NPFFR2 stimulates the stress-related depressive behaviors through HPA axis modulation.

    PubMed

    Lin, Ya-Tin; Liu, Tzu-Yu; Yang, Ching-Yao; Yu, Yu-Lian; Chen, Ting-Chun; Day, Yuan-Ji; Chang, Che-Chien; Huang, Guo-Jen; Chen, Jin-Chung

    2016-09-01

    Neuropeptide FF (NPFF) is a morphine-modulating peptide that regulates the analgesic effect of opioids, and also controls food consumption and cardiovascular function through its interaction with two cognate receptors, NPFFR1 and NPFFR2. In the present study, we explore a novel modulatory role for NPFF-NPFFR2 in stress-related depressive behaviors. In a mouse model of chronic mild stress (CMS)-induced depression, the expression of NPFF significantly increased in the hypothalamus, hippocampus, medial prefrontal cortex (mPFC) and amygdala. In addition, transgenic (Tg) mice over-expressing NPFFR2 displayed clear depression and anxiety-like behaviors with hyperactivity in the hypothalamic-pituitary-adrenal (HPA) axis, reduced expression of glucocorticoid receptor (GR) and neurogenesis in the hippocampus. Furthermore, acute treatment of NPFFR2 agonists in wild-type (WT) mice enhanced the activity of the HPA axis, and chronic administration resulted in depressive and anxiety-like behaviors. Chronic stimulation of NPFFR2 also decreased the expression of hippocampal GR and led to persistent activation of the HPA axis. Strikingly, bilateral intra-paraventricular nucleus (PVN) injection of NPFFR2 shRNA predominately inhibits the depressive-like behavior in CMS-exposed mice. Antidepressants, fluoxetine and ketamine, effectively relieved the depressive behaviors of NPFFR2-Tg mice. We speculate that persistent NPFFR2 activation, in particular in the hypothalamus, up-regulates the HPA axis and results in long-lasting increases in circulating corticosterone (CORT), consequently damaging hippocampal function. This novel role of NPFFR2 in regulating the HPA axis and hippocampal function provides a new avenue for combating depression and anxiety-like disorder.

  8. AMP-Activated Protein Kinase Is Essential for Survival in Chronic Hypoxia

    PubMed Central

    Borger, Darrell R.; Gavrilescu, L. Cristina; Bucur, Maria C.; Ivan, Mircea; DeCaprio, James A.

    2008-01-01

    This study was undertaken to interrogate cancer cell survival during long-term hypoxic stress. Two systems with relevance to carcinogenesis were employed: fully transformed BJ cells, and a renal carcinoma cell line (786-0). The dynamic of AMPK activity was consistent with a prosurvival role during chronic hypoxia. This was further supported by the effects of AMPK agonists and antagonists (AICAR and Compound C). Expression of a dominant-negative AMPK alpha resulted in decreased ATP level, and significantly compromised survival in hypoxia. Dose dependent pro-survival effects of rapamycin were consistent with mTOR inhibition being critical downstream of AMPK in persistent low oxygen. PMID:18359290

  9. Chronic lamotrigine treatment increases rat hippocampal GABA shunt activity and elevates cerebral taurine levels.

    PubMed

    Hassel, B; Taubøll, E; Gjerstad, L

    2001-02-01

    The mechanism of action of the antiepileptic drug lamotrigine has previously been investigated only in acute experiments and is thought to involve inhibition of voltage-dependent sodium channels. However, lamotrigine is effective against more forms of epilepsies than other antiepileptic drugs that also inhibit sodium channels. We investigated whether chronic lamotrigine treatment may affect cerebral amino acid levels. Rats received lamotrigine, 10 mg/kg/day, for 90 days. The hippocampal level of GABA increased 25%, and the activities of glutamate decarboxylase and succinic semialdehyde/GABA transaminase increased 12 and 21% (p< 0.05), respectively, indicating increased GABA turnover. The uptake of GABA and glutamate into proteoliposomes remained unaltered. The level of taurine increased 27% in the hippocampus and 16% in the frontal and parietal cortices. The activities of hexokinase and alpha-ketoglutarate dehydrogenase, remained at control values. Serum lamotrigine was 41.7+/-1.5 microM (mean+/-S.E.M.), which is within the range seen in epileptic patients. Acute experiments with 5, 20 or 100 mg lamotrigine/kg, caused no changes in brain amino acid levels. The results suggest that chronic lamotrigine treatment increases GABAergic activity in the hippocampus. The cerebral increase in taurine, which has neuromodulatory properties, may contribute to the antiepileptic effect of lamotrigine.

  10. Chronic Kappa opioid receptor activation modulates NR2B: Implication in treatment resistant depression

    PubMed Central

    Dogra, Shalini; Kumar, Ajeet; Umrao, Deepmala; Sahasrabuddhe, Amogh A.; Yadav, Prem N.

    2016-01-01

    Psychotomimetic and prodepressive effect by kappa opioid receptor (KOR) activation in rodents and human is widely known. Significantly, recent clinical investigations demonstrated the salutary effects of KOR antagonists in patients with treatment resistant depression, indicating essential role of KOR signaling in refractory depression. This study was undertaken to reveal the molecular determinant of KOR mediated depression and antidepressant response of KOR antagonist. We observed that chronic KOR activation by U50488, a selective KOR agonist, significantly increased depression like symptoms (behavioral despair, anhedonia and sociability) in C57BL/6J mice, which were blocked by KOR antagonist norBNI and antidepressant imipramine, but not by fluoxetine or citalopram. Further, chronic KOR activation increased phosphorylation of NR2B subunit of NMDA at tyrosine 1472 (pNR2B NMDA) in the hippocampus, but not in the cortex. Similar to behavioral effects norBNI and imipramine, but not SSRIs, blocked NR2B phosphorylation. Moreover, KOR induced depression like behaviors were reversed by NR2B selective inhibitor Ro 25-6981. Mechanistic studies in primary cultured neurons and brain tissues using genetic and pharmacological approaches revealed that stimulation of KOR modulates several molecular correlates of depression. Thus, these findings elucidate molecular mechanism of KOR signaling in treatment resistant depression like behaviors in mice. PMID:27634008

  11. Simple platform for chronic imaging of hippocampal activity during spontaneous behaviour in an awake mouse

    PubMed Central

    Villette, Vincent; Levesque, Mathieu; Miled, Amine; Gosselin, Benoit; Topolnik, Lisa

    2017-01-01

    Chronic electrophysiological recordings of neuronal activity combined with two-photon Ca2+ imaging give access to high resolution and cellular specificity. In addition, awake drug-free experimentation is required for investigating the physiological mechanisms that operate in the brain. Here, we developed a simple head fixation platform, which allows simultaneous chronic imaging and electrophysiological recordings to be obtained from the hippocampus of awake mice. We performed quantitative analyses of spontaneous animal behaviour, the associated network states and the cellular activities in the dorsal hippocampus as well as estimated the brain stability limits to image dendritic processes and individual axonal boutons. Ca2+ imaging recordings revealed a relatively stereotyped hippocampal activity despite a high inter-animal and inter-day variability in the mouse behavior. In addition to quiet state and locomotion behavioural patterns, the platform allowed the reliable detection of walking steps and fine speed variations. The brain motion during locomotion was limited to ~1.8 μm, thus allowing for imaging of small sub-cellular structures to be performed in parallel with recordings of network and behavioural states. This simple device extends the drug-free experimentation in vivo, enabling high-stability optophysiological experiments with single-bouton resolution in the mouse awake brain. PMID:28240275

  12. Simple platform for chronic imaging of hippocampal activity during spontaneous behaviour in an awake mouse.

    PubMed

    Villette, Vincent; Levesque, Mathieu; Miled, Amine; Gosselin, Benoit; Topolnik, Lisa

    2017-02-27

    Chronic electrophysiological recordings of neuronal activity combined with two-photon Ca(2+) imaging give access to high resolution and cellular specificity. In addition, awake drug-free experimentation is required for investigating the physiological mechanisms that operate in the brain. Here, we developed a simple head fixation platform, which allows simultaneous chronic imaging and electrophysiological recordings to be obtained from the hippocampus of awake mice. We performed quantitative analyses of spontaneous animal behaviour, the associated network states and the cellular activities in the dorsal hippocampus as well as estimated the brain stability limits to image dendritic processes and individual axonal boutons. Ca(2+) imaging recordings revealed a relatively stereotyped hippocampal activity despite a high inter-animal and inter-day variability in the mouse behavior. In addition to quiet state and locomotion behavioural patterns, the platform allowed the reliable detection of walking steps and fine speed variations. The brain motion during locomotion was limited to ~1.8 μm, thus allowing for imaging of small sub-cellular structures to be performed in parallel with recordings of network and behavioural states. This simple device extends the drug-free experimentation in vivo, enabling high-stability optophysiological experiments with single-bouton resolution in the mouse awake brain.

  13. Protective effect of carnosine after chronic cerebral hypoperfusion possibly through suppressing astrocyte activation

    PubMed Central

    Ma, Jing; Chen, Jihui; Bo, Shuhong; Lu, Xiaotong; Zhang, Jian

    2015-01-01

    Aim: Subcortical ischemic vascular dementia (SIVD) induced by chronic hypoperfusion is a common cause of vascular dementia. The aim of this study was to determine whether the protective effect of carnosine on white matter lesion after chronic cerebral hypoperfusion through suppressing astrocyte activation. Methods: Adult male mice (C57BL/6 strain) were subjected to permanent occlusion of the right unilateral common carotid arteries (rUCCAO) and treated with carnosine or histidine. Open field test, freezing test, Klüver-Barrera staining, immunohistochemical analyses and western blot were performed after rUCCAO. Results: We found that carnosine ameliorated white matter lesion and cognitive impairment after rUCCAO. Carnosine suppressed the activation of astrocyte in both wide type mice and histidine decarboxylase knockout mice. However, administration of histidine did not show the same effect. We found that there were no differences between rUCCAO group and sham group for the expression of glutamate transporter-1 (GLT-1) and glutamate/aspartate transporter (GLAST). Furthermore, carnosine significantly attenuated the increase of inflammatory cytokine interferon gama. Conclusion: These data suggest carnosine induced neuroprotection during SIVD in mice is not dependent on the histaminergic pathway or the regulation of the expression of GLT-1 and GLAST, but may be due to a suppression of astrocyte activation and inflammatory cytokine release. PMID:26885268

  14. Controlled trial of a thymic hormone extract (Thymostimulin) in 'autoimmune' chronic active hepatitis.

    PubMed Central

    Hegarty, J E; Nouri Aria, K T; Eddleston, A L; Williams, R

    1984-01-01

    A randomised controlled trial of thymic hormone extracts (Thymostimulin) (1 mg/kg/day for seven days; 1 mg/kg/weekly thereafter) was undertaken in 30 patients (21 women, nine men) with treated, apparently inactive 'autoimmune' chronic active hepatitis during withdrawal of maintenance corticosteroid and azathioprine therapy. Reactivation of disease occurred in 26 patients (86%) during or after treatment withdrawal and was as frequent in the Thymostimulin treated (11 of 13; 84%) and untreated (15 of 17; 88%; p greater than 0.05) groups. Reactivation of disease was accompanied by a severe defect in concanavalin A induced suppressor cell activity, the magnitude of which was similar in the Thymostimulin treated and untreated groups (mean % suppression = 16.4 and 3.2 respectively; p greater than 0.05 vs 84.4 in control subjects). Further studies assessing the optimal dose, duration of treatment, and mode of administration are required to establish a therapeutic role for thymic hormone extracts in 'autoimmune' chronic active hepatitis. PMID:6230296

  15. Toxicity of chronic high alcohol intake on mouse natural killer cell activity.

    PubMed

    Abdallah, R M; Starkey, J R; Meadows, G G

    1988-02-01

    The toxicity of chronic alcohol intake on natural killer (NK) cell activity of spleen cells from well-nourished, female C57BL/6 mice was studied in a 4-hour cytolytic chromium-release assay against YAC-1 lymphoma cells. Mice were fed a nutritionally complete crystalline amino acid diet and received 20% w/v alcohol solution for 12 weeks. Ad libitum and pair-fed control mice were given diet and either an isocaloric glucose solution or water. Decreased NK cell activity was observed in alcohol-consuming mice relative to all other control groups. NK cell activity was moderately decreased by feeding mice a high glucose diet, but more severely lowered in pair-fed groups compared to ad libitum control groups.

  16. Gene deregulation and chronic activation in natural killer cells deficient in the transcription factor ETS1.

    PubMed

    Ramirez, Kevin; Chandler, Katherine J; Spaulding, Christina; Zandi, Sasan; Sigvardsson, Mikael; Graves, Barbara J; Kee, Barbara L

    2012-06-29

    Multiple transcription factors guide the development of mature functional natural killer (NK) cells, yet little is known about their function. We used global gene expression and genome-wide binding analyses combined with developmental and functional studies to unveil three roles for the ETS1 transcription factor in NK cells. ETS1 functions at the earliest stages of NK cell development to promote expression of critical transcriptional regulators including T-BET and ID2, NK cell receptors (NKRs) including NKp46, Ly49H, and Ly49D, and signaling molecules essential for NKR function. As a consequence, Ets1(-/-) NK cells fail to degranulate after stimulation through activating NKRs. Nonetheless, these cells are hyperresponsive to cytokines and have characteristics of chronic stimulation including increased expression of inhibitory NKRs and multiple activation-associated genes. Therefore, ETS1 regulates a broad gene expression program in NK cells that promotes target cell recognition while limiting cytokine-driven activation.

  17. Monoclonal cryoimmunoglobulin with anti-cytomegalovirus activity associated with T cell chronic lymphocytic leukaemia.

    PubMed Central

    Seigneurin, J M; Renversez, J C; Baccard, M; Seigneurin, D; Micouin, C

    1980-01-01

    A patient with chronic T cell lymphocytic leukaemia developed a monoclonal immunoglobulin (IgG3 kappa = 14 g/l) which was in part cryoprecipitable. At the same time, a subclinical CMV infection occurred which was associated with a neutropenia and thrombocytopenia, and which led to a rise in anti-CMV antibodies. The F(ab')2 fragment of IgG3 kappa, obtained by enzymatic cleavage, was examined for several antiviral activities and it was found to have a strong anti-CMV activity using the immunofluorescence test with anti-kappa conjugate. This is one of the few examples of a cryoglobulin with specific antiviral activity. The leukaemia, possibly together with immunosuppressive therapy, may have been responsible for the uncontrolled proliferation of the clone producing the cryoimmunoglobulin. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:6254708

  18. The PROactive instruments to measure physical activity in patients with chronic obstructive pulmonary disease

    PubMed Central

    Gimeno-Santos, Elena; Raste, Yogini; Demeyer, Heleen; Louvaris, Zafeiris; de Jong, Corina; Rabinovich, Roberto A.; Hopkinson, Nicholas S.; Polkey, Michael I.; Vogiatzis, Ioannis; Tabberer, Maggie; Dobbels, Fabienne; Ivanoff, Nathalie; de Boer, Willem I.; van der Molen, Thys; Kulich, Karoly; Serra, Ignasi; Basagaña, Xavier; Troosters, Thierry; Puhan, Milo A.; Karlsson, Niklas

    2015-01-01

    No current patient-centred instrument captures all dimensions of physical activity in chronic obstructive pulmonary disease (COPD). Our objective was item reduction and initial validation of two instruments to measure physical activity in COPD. Physical activity was assessed in a 6-week, randomised, two-way cross-over, multicentre study using PROactive draft questionnaires (daily and clinical visit versions) and two activity monitors. Item reduction followed an iterative process including classical and Rasch model analyses, and input from patients and clinical experts. 236 COPD patients from five European centres were included. Results indicated the concept of physical activity in COPD had two domains, labelled “amount” and “difficulty”. After item reduction, the daily PROactive instrument comprised nine items and the clinical visit contained 14. Both demonstrated good model fit (person separation index >0.7). Confirmatory factor analysis supported the bidimensional structure. Both instruments had good internal consistency (Cronbach's α>0.8), test–retest reliability (intraclass correlation coefficient ≥0.9) and exhibited moderate-to-high correlations (r>0.6) with related constructs and very low correlations (r<0.3) with unrelated constructs, providing evidence for construct validity. Daily and clinical visit “PROactive physical activity in COPD” instruments are hybrid tools combining a short patient-reported outcome questionnaire and two activity monitor variables which provide simple, valid and reliable measures of physical activity in COPD patients. PMID:26022965

  19. The PROactive instruments to measure physical activity in patients with chronic obstructive pulmonary disease.

    PubMed

    Gimeno-Santos, Elena; Raste, Yogini; Demeyer, Heleen; Louvaris, Zafeiris; de Jong, Corina; Rabinovich, Roberto A; Hopkinson, Nicholas S; Polkey, Michael I; Vogiatzis, Ioannis; Tabberer, Maggie; Dobbels, Fabienne; Ivanoff, Nathalie; de Boer, Willem I; van der Molen, Thys; Kulich, Karoly; Serra, Ignasi; Basagaña, Xavier; Troosters, Thierry; Puhan, Milo A; Karlsson, Niklas; Garcia-Aymerich, Judith

    2015-10-01

    No current patient-centred instrument captures all dimensions of physical activity in chronic obstructive pulmonary disease (COPD). Our objective was item reduction and initial validation of two instruments to measure physical activity in COPD.Physical activity was assessed in a 6-week, randomised, two-way cross-over, multicentre study using PROactive draft questionnaires (daily and clinical visit versions) and two activity monitors. Item reduction followed an iterative process including classical and Rasch model analyses, and input from patients and clinical experts.236 COPD patients from five European centres were included. Results indicated the concept of physical activity in COPD had two domains, labelled "amount" and "difficulty". After item reduction, the daily PROactive instrument comprised nine items and the clinical visit contained 14. Both demonstrated good model fit (person separation index >0.7). Confirmatory factor analysis supported the bidimensional structure. Both instruments had good internal consistency (Cronbach's α>0.8), test-retest reliability (intraclass correlation coefficient ≥0.9) and exhibited moderate-to-high correlations (r>0.6) with related constructs and very low correlations (r<0.3) with unrelated constructs, providing evidence for construct validity.Daily and clinical visit "PROactive physical activity in COPD" instruments are hybrid tools combining a short patient-reported outcome questionnaire and two activity monitor variables which provide simple, valid and reliable measures of physical activity in COPD patients.

  20. Antidepressant-like activity of gallic acid in mice subjected to unpredictable chronic mild stress.

    PubMed

    Chhillar, Ritu; Dhingra, Dinesh

    2013-08-01

    This study was designed to evaluate antidepressant-like activity of gallic acid in Swiss young male albino mice subjected to unpredictable chronic mild stress and to explore the possible underlying mechanisms for this activity. Gallic acid (5, 10, 20 mg/kg, i.p.) and fluoxetine (10 mg/kg, i.p.) per se were administered daily to unstressed mice and other groups of mice subjected to unpredictable mild stress, 30 min after the injection for 21 successive days. The antidepressant-like activity was evaluated using forced swim test (FST) and sucrose preference test. Stress significantly increased immobility period of mice in FST. Gallic acid (10 and 20 mg/kg, i.p.) and fluoxetine significantly decreased immobility period of unstressed and stressed mice in FST and prevented the stress-induced decrease in sucrose preference, indicating significant antidepressant-like activity. There was no significant effect on locomotor activity of the mice by the drugs. Gallic acid (10 and 20 mg/kg, i.p.) significantly decreased Monoamine oxidase-A (MAO-A) activity, malondialdehyde levels, and catalase activity in unstressed mice; and significantly prevented the stress-induced decrease in reduced glutathione and catalase activity; and also significantly prevented stress-induced increase in MAO-A activity, malondialdehyde levels, plasma nitrite, and corticosterone levels. Thus, gallic acid showed antidepressant-like activity in unstressed and stressed mice probably due to its antioxidant activity and through inhibition of MAO-A activity and decrease in plasma nitrite levels. In addition, gallic acid also showed antidepressant-like activity in stressed mice probably through decrease in plasma corticosterone levels.

  1. Increasing Recreational Physical Activity in Patients With Chronic Low Back Pain: A Pragmatic Controlled Clinical Trial.

    PubMed

    Ben-Ami, Noa; Chodick, Gabriel; Mirovsky, Yigal; Pincus, Tamar; Shapiro, Yair

    2017-02-01

    Study Design Prospective, pragmatic, nonrandomized controlled clinical trial. Background Clinical guidelines recommend physical activity for the treatment of chronic low back pain. But engaging patients in physical activity has proven difficult. Known obstacles to physical activity include low self-efficacy and fear avoidance. Objectives This study tested the effectiveness of an enhanced transtheoretical model intervention (ETMI) aimed at increasing recreational physical activity in patients with chronic low back pain, in comparison to usual physical therapy. Methods Patients (n = 220) referred to physical therapy for chronic low back pain were allocated to ETMI or to a control group. The ETMI was delivered by physical therapists and based on behavior-change principles, combined with increased reassurance, therapeutic alliance, and exposure to reduce fear avoidance. The primary outcome was back pain-related disability (Roland-Morris Disability Questionnaire). Secondary outcomes included pain intensity, mental and physical health, and levels of physical activity. Results Intention-to-treat analysis in 189 patients at 12 months indicated that patients in the ETMI group had significantly lower disability compared to usual physical therapy. The difference in mean change from baseline between the interventions was 2.7 points (95% confidence interval: 0.9, 4.5) on the Roland-Morris Disability Questionnaire. At 12 months, worst pain, physical activity, and physical health were all significantly better in patients receiving ETMI. The average number of sessions was 3.5 for the ETMI group and 5.1 for controls. Conclusion Targeting obstacles to physical activity with an intervention that includes components to address self-efficacy and fear avoidance appears to be more effective than usual physical therapy care in reducing long-term disability. Further research is needed to explore the mechanisms that impact outcomes in this intervention package. Level of Evidence Therapy

  2. Effect of Chronic Athletic Activity on Brown Fat in Young Women

    PubMed Central

    Singhal, Vibha; Maffazioli, Giovana D.; Ackerman, Kate E.; Lee, Hang; Elia, Elisa F.; Woolley, Ryan; Kolodny, Gerald; Cypess, Aaron M.; Misra, Madhusmita

    2016-01-01

    Background The effect of chronic exercise activity on brown adipose tissue (BAT) is not clear, with some studies showing positive and others showing negative associations. Chronic exercise is associated with increased resting energy expenditure (REE) secondary to increased lean mass and a probable increase in BAT. Many athletes are in a state of relative energy deficit suggested by lower fat mass and hypothalamic amenorrhea. States of severe energy deficit such as anorexia nervosa are associated with reduced BAT. There are no data regarding the impact of chronic exercise activity on BAT volume or activity in young women and it is unclear whether relative energy deficiency modifies the effects of exercise on BAT. Purpose We assessed cold induced BAT volume and activity in young female athletes compared with non-athletes, and further evaluated associations of BAT with measures of REE, body composition and menstrual status. Methods The protocol was approved by our Institutional Review Board. Written informed consent was obtained from all participants prior to study initiation. This was a cross-sectional study of 24 women (16 athletes and8 non-athletes) between 18–25 years of age. Athletes were either oligo-amenorrheic (n = 8) or eumenorrheic (n = 8).We used PET/CT scans to determine cold induced BAT activity, VMAX Encore 29 metabolic cart to obtain measures of REE, and DXA for body composition. Results Athletes and non-athletes did not differ for age or BMI. Compared with non-athletes, athletes had lower percent body fat (p = 0.002), higher percent lean mass (p = 0.01) and trended higher in REE (p = 0.09). BAT volume and activity in athletes trended lower than in non-athletes (p = 0.06; p = 0.07, respectively). We found negative associations of BAT activity with duration of amenorrhea (r = -0.46, p = 0.02).BAT volume correlated inversely with lean mass (r = -0.46, p = 0.02), and positively with percent body fat, irisin and thyroid hormones. Conclusions Our study

  3. Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma.

    PubMed

    Davis, R Eric; Ngo, Vu N; Lenz, Georg; Tolar, Pavel; Young, Ryan M; Romesser, Paul B; Kohlhammer, Holger; Lamy, Laurence; Zhao, Hong; Yang, Yandan; Xu, Weihong; Shaffer, Arthur L; Wright, George; Xiao, Wenming; Powell, John; Jiang, Jian-Kang; Thomas, Craig J; Rosenwald, Andreas; Ott, German; Muller-Hermelink, Hans Konrad; Gascoyne, Randy D; Connors, Joseph M; Johnson, Nathalie A; Rimsza, Lisa M; Campo, Elias; Jaffe, Elaine S; Wilson, Wyndham H; Delabie, Jan; Smeland, Erlend B; Fisher, Richard I; Braziel, Rita M; Tubbs, Raymond R; Cook, J R; Weisenburger, Dennis D; Chan, Wing C; Pierce, Susan K; Staudt, Louis M

    2010-01-07

    A role for B-cell-receptor (BCR) signalling in lymphomagenesis has been inferred by studying immunoglobulin genes in human lymphomas and by engineering mouse models, but genetic and functional evidence for its oncogenic role in human lymphomas is needed. Here we describe a form of 'chronic active' BCR signalling that is required for cell survival in the activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL). The signalling adaptor CARD11 is required for constitutive NF-kappaB pathway activity and survival in ABC DLBCL. Roughly 10% of ABC DLBCLs have mutant CARD11 isoforms that activate NF-kappaB, but the mechanism that engages wild-type CARD11 in other ABC DLBCLs was unknown. An RNA interference genetic screen revealed that a BCR signalling component, Bruton's tyrosine kinase, is essential for the survival of ABC DLBCLs with wild-type CARD11. In addition, knockdown of proximal BCR subunits (IgM, Ig-kappa, CD79A and CD79B) killed ABC DLBCLs with wild-type CARD11 but not other lymphomas. The BCRs in these ABC DLBCLs formed prominent clusters in the plasma membrane with low diffusion, similarly to BCRs in antigen-stimulated normal B cells. Somatic mutations affecting the immunoreceptor tyrosine-based activation motif (ITAM) signalling modules of CD79B and CD79A were detected frequently in ABC DLBCL biopsy samples but rarely in other DLBCLs and never in Burkitt's lymphoma or mucosa-associated lymphoid tissue lymphoma. In 18% of ABC DLBCLs, one functionally critical residue of CD79B, the first ITAM tyrosine, was mutated. These mutations increased surface BCR expression and attenuated Lyn kinase, a feedback inhibitor of BCR signalling. These findings establish chronic active BCR signalling as a new pathogenetic mechanism in ABC DLBCL, suggesting several therapeutic strategies.

  4. Adult Female Rats Altered Diurnal Locomotor Activity Pattern Following Chronic Methylphenidate Treatment

    PubMed Central

    Trinh, T.; Kohllepin, S; Yang, P.B.; Burau, K.D.; Dafny, N.

    2014-01-01

    Methylphenidate (MPD) is one of the most prescribed pharmacological agents and also used as cognitive enhancement and for recreational purposes. The objective of this study was to investigate the repetitive dose-response effects of MPD on rhythm locomotor activity pattern of female WKY rats and compare to prior study done on male. The hypothesis is that change in the circadian activity pattern indicates a long-lasting effect of the drug. Four animal groups (saline control, 0.6, 2.5, and 10.0 mg/kg MPD dose groups) were housed in a sound-controlled room at 12:12 light/dark cycle. All received saline injections on experimental day 1 (ED 1). On EDs 2-7, the control group received saline injection; the other groups received 0.6, 2.5, or 10.0 mg/kg MPD, respectively. On ED 8-10, injections were withheld. On ED 11, each group received the same dose as EDs 2-7. Hourly histograms and cosine statistical analyses calculating the acrophase (ϕ), amplitude (A), and MESOR (M) were applied to assess the 24-hour circadian activity pattern. The 0.6 and 2.5 mg/kg MPD groups exhibited significant (p<0.05) change in their circadian activity pattern on ED 11. The 10.0 mg/kg MPD group exhibited tolerance on ED 11 and also a significant change in activity pattern on ED 8 compared to ED 1, consistent with withdrawal behavior (p<0.007). In conclusion, chronic MPD administration alters circadian locomotor activity of adult female WKY rats and confirms that chronic MPD use elicits long lasting effects PMID:23893293

  5. Experimental pulmonary granuloma mimicking sarcoidosis induced by Propionibacterium acnes in mice.

    PubMed

    Iio, Kouji; Iio, Tomoe Ueno; Okui, Yuhei; Ichikawa, Hirohisa; Tanimoto, Yasushi; Miyahara, Nobuaki; Kanehiro, Arihiko; Tanimoto, Mitsune; Nakata, Yasunari; Kataoka, Mikio

    2010-04-01

    Propionibacterium acnes has been implicated as an etiologic agent of sarcoidosis since the isolation of this bacterium from sarcoid lesions. We experimentally produced a murine pulmonary granuloma model using P. acnes with several features that simulate sarcoidosis. Mice were sensitized with heat-killed P. acnes and complete Freund's adjuvant and were subsequently challenged with heat-killed P. acnes at 2-week intervals. P. acnes-challenged mice developed epitheloid cell granulomas in the lungs. These mice showed a pulmonary immune response characterized by an increased number of T-lymphocytes, especially CD4+ cells, and the ratio of CD4+/CD8+ in bronchoalveolar lavage (BAL) fluid also increased. Furthermore, significant elevations in both angiotensin-converting enzyme (ACE) serum levels and antibody titers against P. acnes were observed. Mice sensitized with P. acnes without complete Freund's adjuvant were capable of forming pulmonary granulomas, which appeared to be caused by indigenous P. acnes. The genome of P. acnes was found in the lungs, BAL cells, hilar lymph nodes, liver, and spleen in non-sensitized mice, which were thought to be germ-free. These results suggest that the immune response against indigenous P. acnes may play an important role in the pathogenesis of granuloma formation in a murine model.

  6. [Impact of various millimeter-range electromagnetic radiation schedules on immunological parameters in patients with respiratory sarcoidosis].

    PubMed

    Borisov, S B; Shpykov, A S; Terent'eva, N A

    2007-01-01

    The paper analyzes the impact of various millimeter-range electromagnetic radiation schedules on immunological parameters in 152 patients with new-onset respiratory sarcoidosis. It shows that the immunomodulatory effect of millimeter-range therapy depends on the treatment regimen chosen. There is evidence for the advantages of millimeter-range noise electromagnetic radiation.

  7. Formulation and quality control of semi-solid containing harmless bacteria by-products: chronic wounds pro-healing activity.

    PubMed

    Sesto Cabral, Maria Eugenia; Ramos, Alberto Nicolas; Macedo, Alexandre Jose; Trentin, Danielle S; Treter, Janine; Manzo, Ruben H; Valdez, Juan Carlos

    2014-07-08

    Abstract Chronic wounds are those that remain in a chronic inflammatory state and fail to follow normal healing process. Infection is one of the most important causes of chronicity. A frequent pathogen isolated from chronic infections is Pseudomonas aeruginosa; refractory to therapy and host immune attack in its biofilm phenotype. Lactobacillus plantarum cultures supernatants (LAPS) interfere with its pathogenic capacity. In addition, LAPS showed bacteriostatic and bactericide properties and is neither cytotoxic nor an inductor of necrosis-apoptosis. LAPSs chemical composition was determined; allowing us to propose a correlation between its constituents and their biological activity. This article shows a pharmaceutical dosage form designed by using LAPS as an API with pro-healing activity and its quality control. Pharmacotechnical and anti-microbial assays were adapted to demonstrate that the vehicle used does not modify LAPS activities. Selected formulation (F100) showed fair mechanical and technological properties. From the in vitro release assays was found an adequate release from the carrier matrix and maintains its anti-pathogenic activity for 6 months. We propose F100 for chronic wounds treatment. The use of harmless bacteria by-products, such as LAPS, to antagonize infectious pathogens that have ability to form biofilm is an efficient and economic approach to treat infected chronic wounds.

  8. Altered activity of heme biosynthesis pathway enzymes in individuals chronically exposed to arsenic in Mexico.

    PubMed

    Hernández-Zavala, A; Del Razo, L M; García-Vargas, G G; Aguilar, C; Borja, V H; Albores, A; Cebrián, M E

    1999-03-01

    Our objective was to evaluate the activities of some enzymes of the heme biosynthesis pathway and their relationship with the profile of urinary porphyrin excretion in individuals exposed chronically to arsenic (As) via drinking water in Region Lagunera, Mexico. We selected 17 individuals from each village studied: Benito Juarez, which has current exposure to 0.3 mg As/l; Santa Ana, where individuals have been exposed for more than 35 years to 0.4 mg As/l, but due to changes in the water supply (in 1992) exposure was reduced to its current level (0.1 mg As/l), and Nazareno, with 0.014 mg As/l. Average arsenic concentrations in urine were 2058, 398, and 88 microg As/g creatinine, respectively. The more evident alterations in heme metabolism observed in the highly exposed individuals were: (1) small but significant increases in porphobilinogen deaminase (PBG-D) and uroporphyrinogen decarboxylase (URO-D) activities in peripheral blood erythrocytes; (2) increases in the urinary excretion of total porphyrins, mainly due to coproporphyrin III (COPROIII) and uroporphyrin III (UROIII); and (3) increases in the COPRO/URO and COPROIII/COPROI ratios. No significant changes were observed in uroporphyrinogen III synthetase (UROIII-S) activity. The direct relationships between enzyme activities and urinary porphyrins, suggest that the increased porphyrin excretion was related to PBG-D, whereas the increased URO-D activity would enhance coproporphyrin synthesis and excretion at the expense of uroporphyrin. None of the human studies available have reported the marked porphyric response and enzyme inhibition observed in rodents. In conclusion, chronic As exposure alters human heme metabolism; however the severity of the effects appears to depend on characteristics of exposure not yet fully characterized.

  9. Rifapentine is not more active than rifampin against chronic tuberculosis in guinea pigs.

    PubMed

    Dutta, Noton K; Illei, Peter B; Peloquin, Charles A; Pinn, Michael L; Mdluli, Khisimuzi E; Nuermberger, Eric L; Grosset, Jacques H; Karakousis, Petros C

    2012-07-01

    Rifamycins are key sterilizing drugs in the current treatment of active tuberculosis (TB). Daily dosing of rifapentine (P), a potent rifamycin with high intracellular accumulation, in place of rifampin (R) in the standard antitubercular regimen significantly shortens the duration of treatment needed to prevent relapse in a murine model of active TB. We undertook the current study to compare directly the activities of human-equivalent doses of P and R in a guinea pig model of chronic TB, in which bacilli are predominantly extracellular within human-like necrotic granulomas. Hartley strain guinea pigs were aerosol infected with ~200 bacilli of Mycobacterium tuberculosis H37Rv, and treatment given 5 days/week was initiated 6 weeks later. R at 100 mg/kg of body weight and P at 100 mg/kg were given orally alone or in combination with isoniazid (H) at 60 mg/kg and pyrazinamide (Z) at 300 mg/kg. Culture-positive relapse was assessed in subgroups of guinea pigs after completion of 1 and 2 months of treatment. Human-equivalent doses of R and P showed equivalent bactericidal activity when used alone and in combination therapy. In guinea pigs treated with rifampin, isoniazid, and pyrazinamide (RHZ) or PHZ, microbiological relapse occurred in the lungs of 8/10 animals treated for 1 month and in 0/10 animals treated for 2 months. Substitution of P for R in the standard antitubercular regimen did not shorten the time to cure in this guinea pig model of chronic TB. Data from ongoing clinical trials comparing the activity of these two drugs are awaited to determine the relevance of the guinea pig TB model in preclinical drug screening.

  10. Rifapentine Is Not More Active than Rifampin against Chronic Tuberculosis in Guinea Pigs

    PubMed Central

    Dutta, Noton K.; Illei, Peter B.; Peloquin, Charles A.; Pinn, Michael L.; Mdluli, Khisimuzi E.; Nuermberger, Eric L.; Grosset, Jacques H.

    2012-01-01

    Rifamycins are key sterilizing drugs in the current treatment of active tuberculosis (TB). Daily dosing of rifapentine (P), a potent rifamycin with high intracellular accumulation, in place of rifampin (R) in the standard antitubercular regimen significantly shortens the duration of treatment needed to prevent relapse in a murine model of active TB. We undertook the current study to compare directly the activities of human-equivalent doses of P and R in a guinea pig model of chronic TB, in which bacilli are predominantly extracellular within human-like necrotic granulomas. Hartley strain guinea pigs were aerosol infected with ∼200 bacilli of Mycobacterium tuberculosis H37Rv, and treatment given 5 days/week was initiated 6 weeks later. R at 100 mg/kg of body weight and P at 100 mg/kg were given orally alone or in combination with isoniazid (H) at 60 mg/kg and pyrazinamide (Z) at 300 mg/kg. Culture-positive relapse was assessed in subgroups of guinea pigs after completion of 1 and 2 months of treatment. Human-equivalent doses of R and P showed equivalent bactericidal activity when used alone and in combination therapy. In guinea pigs treated with rifampin, isoniazid, and pyrazinamide (RHZ) or PHZ, microbiological relapse occurred in the lungs of 8/10 animals treated for 1 month and in 0/10 animals treated for 2 months. Substitution of P for R in the standard antitubercular regimen did not shorten the time to cure in this guinea pig model of chronic TB. Data from ongoing clinical trials comparing the activity of these two drugs are awaited to determine the relevance of the guinea pig TB model in preclinical drug screening. PMID:22547623

  11. Acute and chronic caffeine administration increases physical activity in sedentary adults.

    PubMed

    Schrader, Patrick; Panek, Leah M; Temple, Jennifer L

    2013-06-01

    Caffeine is a commonly used stimulant thought to have ergogenic properties. Most studies on the ergogenic effects of caffeine have been conducted in athletes. The purpose of this study was to test the hypothesis that caffeine reduces ratings of perceived exertion and increases liking of physical activity in sedentary adults. Participants completed treadmill walking at 60% to 70% of their maximal heart rate at baseline and for 6 subsequent visits, during which half of the participants were given caffeine (3 mg/kg) and half given placebo in a sports drink vehicle. To investigate the potential synergistic effects of acute and chronic caffeine on self-determined exercise duration, participants were rerandomized to either the same or different condition for the last visit, creating 4 chronic/acute treatment groups (placebo/placebo, placebo/caffeine, caffeine/placebo, caffeine/caffeine). Participants rated how much they liked the activity and perceived exertion at each visit. There was a main effect of time on liking of physical activity, with liking increasing over time and an interaction of sex and caffeine treatment on liking, with liking of activity increasing in female participants treated with caffeine, but not with placebo. There was no effect of caffeine on ratings of perceived exertion. Individuals who received caffeine on the final test day exercised for significantly longer than those who received placebo. These data suggest that repeated exposure to physical activity significantly increases liking of exercise and reduces ratings of perceived exertion and that caffeine does little to further modify these effects.

  12. Validating Accelerometry as a Measure of Physical Activity and Energy Expenditure in Chronic Stroke

    PubMed Central

    Serra, Monica C.; Balraj, Elizabeth; DiSanzo, Beth L.; Ivey, Frederick M.; Hafer-Macko, Charlene E.; Treuth, Margarita S.; Ryan, Alice S.

    2016-01-01

    Background Accelerometers can objectively measure steps taken per day in individuals without gait deficits, but accelerometers also have the ability to estimate frequency, intensity, and duration of physical activity. However, thresholds to distinguish varying levels of activity intensity using the Actical brand accelerometer are standardized only for the general population and may underestimate intensity in stroke. Objective To derive Actical activity count thresholds specific to stroke disability for use in more accurately gauging time spent at differing activity levels. Methods Men (n=18) and women (n=10) with chronic hemiparetic gait (4±2 years latency, 43% Caucasian, 56% African American, ages of 47–83 yrs, BMI 19 – 48 kg/m2) participated in the study. Actical accelerometers were placed on the non-paretic hip to obtain accelerometry counts during eight activities of varying intensity: 1) watching TV; 2) seated stretching; 3) standing stretching; 4) floor sweeping; 5) stepping in place; 6) over-ground walking; 7) lower speed treadmill walking (1.0 mph at 4% incline); and 8) higher speed treadmill walking (2.0 mph at 4% incline). Simultaneous portable monitoring (Cosmed K4b2) enabled quantification of energy cost for each activity in metabolic equivalents (METs, or oxygen consumption in multiples of resting level). Measurements were obtained for 10 min of standard rest and 5 minutes during each of the eight activities. Results Regression analysis yielded the following new stroke-specific Actical minimum thresholds: 125 counts per minute (cpm) for sedentary/light activity, 667 cpm for light/moderate activity, and 1546 cpm for moderate/vigorous activity. Conclusion Our revised cut-points better reflect activity levels after stroke and suggest significantly lower thresholds relative to those observed for the general population of healthy individuals. We conclude that the standard, commonly applied Actical thresholds are inappropriate for this unique population

  13. Regulation of B cell fate by chronic activity of the IgE B cell receptor

    PubMed Central

    Yang, Zhiyong; Robinson, Marcus J; Chen, Xiangjun; Smith, Geoffrey A; Taunton, Jack; Liu, Wanli; Allen, Christopher D C

    2016-01-01

    IgE can trigger potent allergic responses, yet the mechanisms regulating IgE production are poorly understood. Here we reveal that IgE+ B cells are constrained by chronic activity of the IgE B cell receptor (BCR). In the absence of cognate antigen, the IgE BCR promoted terminal differentiation of B cells into plasma cells (PCs) under cell culture conditions mimicking T cell help. This antigen-independent PC differentiation involved multiple IgE domains and Syk, CD19, BLNK, Btk, and IRF4. Disruption of BCR signaling in mice led to consistently exaggerated IgE+ germinal center (GC) B cell but variably increased PC responses. We were unable to confirm reports that the IgE BCR directly promoted intrinsic apoptosis. Instead, IgE+ GC B cells exhibited poor antigen presentation and prolonged cell cycles, suggesting reduced competition for T cell help. We propose that chronic BCR activity and access to T cell help play critical roles in regulating IgE responses. DOI: http://dx.doi.org/10.7554/eLife.21238.001 PMID:27935477

  14. Functional biopolymer-based matrices for modulation of chronic wound enzyme activities.

    PubMed

    Francesko, Antonio; Soares da Costa, Diana; Reis, Rui L; Pashkuleva, Iva; Tzanov, Tzanko

    2013-02-01

    Collagen, collagen/hyaluronic acid (HA) and collagen/HA/chitosan (CS) sponges loaded with epigallocatechin gallate (EGCG), catechin (CAT) and gallic acid (GA) were developed and evaluated as active chronic wound dressings. Their physico-mechanical properties, biostability, biocompatibility and ability to inhibit in vitro myeloperoxidase (MPO) and collagenase--major enzymes related with the persistent inflammation in chronic wounds--were investigated as a function of the biopolymer composition and the polyphenolic compound used. The results demonstrated that the molecular weight of HA influences significantly the bulk properties of the obtained materials: higher elastic modulus, swelling ability and biostability against collagenase were measured when HA with higher molecular weights (830 and 2000 kDa) were added to the collagen matrices. The addition of CS and the polyphenols increased further the biostability of the sponges. Preliminary in vitro tests with fibroblasts revealed that the cells were able to adhere to all sponges. Cell viability was not affected significantly by the addition of the polyphenols; however, the presence of CS or high molecular weight HA in the sponge composition was associated with lower cellular viability. Finally, all specimens containing polyphenols efficiently inhibited the MPO activity. The highest inhibition capacity was observed for EGCG (IC₅₀=15±1μM) and it was coupled to the highest extent of binding to the biopolymers (>80%) and optimal release profile from the sponges that allowed for prolonged (up to 3-5 days) effects.

  15. Regulation of B cell fate by chronic activity of the IgE B cell receptor.

    PubMed

    Yang, Zhiyong; Robinson, Marcus J; Chen, Xiangjun; Smith, Geoffrey A; Taunton, Jack; Liu, Wanli; Allen, Christopher D C

    2016-12-09

    IgE can trigger potent allergic responses, yet the mechanisms regulating IgE production are poorly understood. Here we reveal that IgE(+) B cells are constrained by chronic activity of the IgE B cell receptor (BCR). In the absence of cognate antigen, the IgE BCR promoted terminal differentiation of B cells into plasma cells (PCs) under cell culture conditions mimicking T cell help. This antigen-independent PC differentiation involved multiple IgE domains and Syk, CD19, BLNK, Btk, and IRF4. Disruption of BCR signaling in mice led to consistently exaggerated IgE(+) germinal center (GC) B cell but variably increased PC responses. We were unable to confirm reports that the IgE BCR directly promoted intrinsic apoptosis. Instead, IgE(+) GC B cells exhibited poor antigen presentation and prolonged cell cycles, suggesting reduced competition for T cell help. We propose that chronic BCR activity and access to T cell help play critical roles in regulating IgE responses.

  16. Chronic ethanol consumption inhibits glucokinase transcriptional activity by Atf3 and triggers metabolic syndrome in vivo.

    PubMed

    Kim, Ji Yeon; Hwang, Joo-Yeon; Lee, Dae Yeon; Song, Eun Hyun; Park, Keon Jae; Kim, Gyu Hee; Jeong, Eun Ae; Lee, Yoo Jeong; Go, Min Jin; Kim, Dae Jin; Lee, Seong Su; Kim, Bong-Jo; Song, Jihyun; Roh, Gu Seob; Gao, Bin; Kim, Won-Ho

    2014-09-26

    Chronic ethanol consumption induces pancreatic β-cell dysfunction through glucokinase (Gck) nitration and down-regulation, leading to impaired glucose tolerance and insulin resistance, but the underlying mechanism remains largely unknown. Here, we demonstrate that Gck gene expression and promoter activity in pancreatic β-cells were suppressed by chronic ethanol exposure in vivo and in vitro, whereas expression of activating transcription factor 3 (Atf3) and its binding to the putative Atf/Creb site (from -287 to -158 bp) on the Gck promoter were up-regulated. Furthermore, in vitro ethanol-induced Atf3 inhibited the positive effect of Pdx-1 on Gck transcriptional regulation, enhanced recruitment of Hdac1/2 and histone H3 deacetylation, and subsequently augmented the interaction of Hdac1/Pdx-1 on the Gck promoter, which were diminished by Atf3 siRNA. In vivo Atf3-silencing reversed ethanol-mediated Gck down-regulation and β-cell dysfunction, followed by the amelioration of impaired glucose tolerance and insulin resistance. Together, we identified that ethanol-induced Atf3 fosters β-cell dysfunction via Gck down-regulation and that its loss ameliorates metabolic syndrome and could be a potential therapeutic target in treating type 2 diabetes. The Atf3 gene is associated with the induction of type 2 diabetes and alcohol consumption-induced metabolic impairment and thus may be the major negative regulator for glucose homeostasis.

  17. The effects of chronic achievement motivation and achievement primes on the activation of achievement and fun goals.

    PubMed

    Hart, William; Albarracín, Dolores

    2009-12-01

    This research examined the hypothesis that situational achievement cues can elicit achievement or fun goals depending on chronic differences in achievement motivation. In 4 studies, chronic differences in achievement motivation were measured, and achievement-denoting words were used to influence behavior. The effects of these variables were assessed on self-report inventories, task performance, task resumption following an interruption, and the pursuit of means relevant to achieving or having fun. Findings indicated that achievement priming (vs. control priming) activated a goal to achieve and inhibited a goal to have fun in individuals with chronically high-achievement motivation but activated a goal to have fun and inhibited a goal to achieve in individuals with chronically low-achievement motivation.

  18. The Effects of Chronic Achievement Motivation and Achievement Primes on the Activation of Achievement and Fun Goals

    PubMed Central

    Hart, William; Albarracín, Dolores

    2013-01-01

    This research examined the hypothesis that situational achievement cues can elicit achievement or fun goals depending on chronic differences in achievement motivation. In 4 studies, chronic differences in achievement motivation were measured, and achievement-denoting words were used to influence behavior. The effects of these variables were assessed on self-report inventories, task performance, task resumption following an interruption, and the pursuit of means relevant to achieving or having fun. Findings indicated that achievement priming (vs. control priming) activated a goal to achieve and inhibited a goal to have fun in individuals with chronically high-achievement motivation but activated a goal to have fun and inhibited a goal to achieve in individuals with chronically low-achievement motivation. PMID:19968423

  19. Infliximab therapy balances regulatory T cells, tumour necrosis factor receptor 2 (TNFR2) expression and soluble TNFR2 in sarcoidosis.

    PubMed

    Verwoerd, A; Hijdra, D; Vorselaars, A D M; Crommelin, H A; van Moorsel, C H M; Grutters, J C; Claessen, A M E

    2016-08-01

    Sarcoidosis is a systemic granulomatous disease of unknown aetiology that most commonly affects the lungs. Although elevated levels of regulatory T cells (Tregs ) have been reported, the extent to which they play a role in sarcoidosis pathogenesis remains unclear. Tumour necrosis factor (TNF) is thought to be one of the driving forces behind granuloma formation, illustrated by the efficacy of infliximab in severe sarcoidosis. Tregs express TNF receptor 2 (TNFR2) highly. Here, we examined the influence of infliximab therapy on Tregs and (soluble) TNFR2 levels in sarcoidosis, and correlated these with response to therapy. We observed that relative frequencies of Tregs were significantly higher in patients (n = 54) compared to healthy controls (n = 26; median 6·73 versus 4·36%; P < 0·001) and decreased following therapy (4·95; P < 0·001). Baseline TNFR2 expression on Tregs was increased significantly in patients versus controls (99·4 versus 96·2%; P = 0·031), and also in responders to therapy versus non-responders (99·6 versus 97·3%; P = 0·012). Furthermore, baseline soluble TNFR2 (sTNFR2) was higher in responders than in non-responders (mean 174 versus 107 pg/ml; P = 0·015). After treatment, responders showed a significant reduction in sTNFR2 levels in peripheral blood (-44·7 pg/ml; P < 0·001), in contrast to non-responders (+3·59 pg/ml). Our results demonstrated that Treg frequencies and TNFR2 expression on Tregs are increased in sarcoidosis, followed by a decline during infliximab therapy, suggesting a pathophysiological role of this T cell subset. Interestingly, sTNFR2 levels at baseline differed significantly between responders and non-responders, making it a potential marker in predicting which patients might benefit from infliximab.

  20. The Serum Expression of Selected miRNAs in Pulmonary Sarcoidosis with/without Löfgren's Syndrome

    PubMed Central

    Novosadova, Eva; Chabronova, Alzbeta; Kolek, Vitezslav

    2016-01-01

    Purpose. Pulmonary sarcoidosis is associated with dysregulated expression of intracellular miRNAs. There is however only little information on extracellular miRNAs and their association with the disease course in sarcoidosis. We therefore assessed serum miRNAs in sarcoidosis classified according to the presence of Löfgren's syndrome (LS) as a hallmark of good prognosis in contrast to more advanced disease course. Methods. RT-PCR was used to assess 35 miRNAs in 13 healthy controls and 24 sarcoidosis patients (12 with X-ray (CXR) stage ≤ 1 and LS and 12 with insidious onset and CXR stage ≥ 3). Results. Compared to controls, we consistently observed dysregulated expressions of miR-146, miR-16, miR-425-5p, and miR-93-5p in both sarcoidosis groups irrespective of disease course. Specifically, patients without LS had dysregulated expressions of miR-150-5p, miR-1, and miR-212 compared to controls. Patients with LS had dysregulated expressions of miR-21-5p and miR-340-5p compared to controls. Bioinformatics predicted consistently “Pathways in cancer” to be modulated by both altered profiles in patients with/without LS. Three miRNAs (miR-21-5p, miR-340-5p, and miR-212-3p) differed between our patients with LS and those without LS; their cumulative effect may modulate “TGF-β signalling pathway.” Conclusions. Further study should focus on possible applications of serum miRNAs for diagnostics follow-up and for prognosis. PMID:28050119

  1. Translating active living research into policy and practice: one important pathway to chronic disease prevention.

    PubMed

    Giles-Corti, Billie; Sallis, James F; Sugiyama, Takemi; Frank, Lawrence D; Lowe, Melanie; Owen, Neville

    2015-05-01

    Global concerns about rising levels of chronic disease make timely translation of research into policy and practice a priority. There is a need to tackle common risk factors: tobacco use, unhealthy diets, physical inactivity, and harmful alcohol use. Using evidence to inform policy and practice is challenging, often hampered by a poor fit between academic research and the needs of policymakers and practitioners--notably for active living researchers whose objective is to increase population physical activity by changing the ways cities are designed and built. We propose 10 strategies that may facilitate translation of research into health-enhancing urban planning policy. Strategies include interdisciplinary research teams of policymakers and practitioners; undertaking explicitly policy-relevant research; adopting appropriate study designs and methodologies (evaluation of policy initiatives as 'natural experiments'); and adopting dissemination strategies that include knowledge brokers, advocates, and lobbyists. Conducting more policy-relevant research will require training for researchers as well as different rewards in academia.

  2. Idelalisib and caffeine reduce suppression of T cell responses mediated by activated chronic lymphocytic leukemia cells

    PubMed Central

    Hock, Barry D.; MacPherson, Sean A.; McKenzie, Judith L.

    2017-01-01

    Chronic lymphocytic leukemia (CLL) is associated with T cell dysfunction. Activated CLL cells are found within the lymphoid tumor micro-environment and overcoming immuno-suppression induced by these cells may improve anti-CLL immune responses. However, the mechanisms by which activated CLL cells inhibit T cell responses, and reagents targeting such mechanisms have not been identified. Here we demonstrate that the ability of in vitro activated CLL cells to suppress T cell proliferation is not reversed by the presence of ecto-nuclease inhibitors or blockade of IL-10, PD-1 and CTLA-4 pathways. Caffeine is both an adenosine receptor antagonist and a phosphatidylinositol-3-kinase, p110δ (PI3Kδ) inhibitor and, at physiologically relevant levels, significantly reversed suppression. Significant reversal of suppression was also observed with the PI3Kδ specific inhibitor Idelalisib but not with adenosine receptor specific antagonists. Furthermore, addition of caffeine or Idelalisib to activated CLL cells significantly inhibited phosphorylation of AKT, a downstream kinase of PI3K, but did not affect CLL viability. These results suggest that caffeine, in common with Idelalisib, reduces the immuno-suppressive activity of activated CLL cells by inhibiting PI3Kδ. These findings raise the possibility that these compounds may provide a useful therapeutic adjunct by reducing immuno-suppression within the tumor micro-environment of CLL. PMID:28257435

  3. Oxidized Phospholipid OxPAPC Activates TRPA1 and Contributes to Chronic Inflammatory Pain in Mice.

    PubMed

    Liu, Boyi; Tai, Yan; Caceres, Ana I; Achanta, Satyanarayana; Balakrishna, Shrilatha; Shao, Xiaomei; Fang, Junfan; Jordt, Sven-Eric

    2016-01-01

    Oxidation products of the naturally occurring phospholipid 1-palmitoyl-2-arachidonoyl-sn-glycerol-3-phosphatidylcholine (PAPC), which are known as OxPAPC, accumulate in atherosclerotic lesions and at other sites of inflammation in conditions such as septic inflammation and acute lung injury to exert pro- or anti-inflammatory effects. It is currently unknown whether OxPAPC also contributes to inflammatory pain and peripheral neuronal excitability in these conditions. Here, we observed that OxPAPC dose-dependently and selectively activated human TRPA1 nociceptive ion channels expressed in HEK293 cells in vitro, without any effect on other TRP channels, including TRPV1, TRPV4 and TRPM8. OxPAPC agonist activity was dependent on essential cysteine and lysine residues within the N-terminus of the TRPA1 channel protein. OxPAPC activated calcium influx into a subset of mouse sensory neurons which were also sensitive to the TRPA1 agonist mustard oil. Neuronal OxPAPC responses were largely abolished in neurons isolated from TRPA1-deficient mice. Intraplantar injection of OxPAPC into the mouse hind paw induced acute pain and persistent mechanical hyperalgesia and this effect was attenuated by the TRPA1 inhibitor, HC-030031. More importantly, we found levels of OxPAPC to be significantly increased in inflamed tissue in a mouse model of chronic inflammatory pain, identified by the binding of an OxPAPC-specific antibody. These findings suggest that TRPA1 is a molecular target for OxPAPC and OxPAPC may contribute to chronic inflammatory pain through TRPA1 activation. Targeting against OxPAPC and TRPA1 signaling pathway may be promising in inflammatory pain treatment.

  4. Oxidized Phospholipid OxPAPC Activates TRPA1 and Contributes to Chronic Inflammatory Pain in Mice

    PubMed Central

    Liu, Boyi; Tai, Yan; Caceres, Ana I.; Achanta, Satyanarayana; Balakrishna, Shrilatha; Shao, Xiaomei; Fang, Junfan

    2016-01-01

    Oxidation products of the naturally occurring phospholipid 1-palmitoyl-2-arachidonoyl-sn-glycerol-3-phosphatidylcholine (PAPC), which are known as OxPAPC, accumulate in atherosclerotic lesions and at other sites of inflammation in conditions such as septic inflammation and acute lung injury to exert pro- or anti-inflammatory effects. It is currently unknown whether OxPAPC also contributes to inflammatory pain and peripheral neuronal excitability in these conditions. Here, we observed that OxPAPC dose-dependently and selectively activated human TRPA1 nociceptive ion channels expressed in HEK293 cells in vitro, without any effect on other TRP channels, including TRPV1, TRPV4 and TRPM8. OxPAPC agonist activity was dependent on essential cysteine and lysine residues within the N-terminus of the TRPA1 channel protein. OxPAPC activated calcium influx into a subset of mouse sensory neurons which were also sensitive to the TRPA1 agonist mustard oil. Neuronal OxPAPC responses were largely abolished in neurons isolated from TRPA1-deficient mice. Intraplantar injection of OxPAPC into the mouse hind paw induced acute pain and persistent mechanical hyperalgesia and this effect was attenuated by the TRPA1 inhibitor, HC-030031. More importantly, we found levels of OxPAPC to be significantly increased in inflamed tissue in a mouse model of chronic inflammatory pain, identified by the binding of an OxPAPC-specific antibody. These findings suggest that TRPA1 is a molecular target for OxPAPC and OxPAPC may contribute to chronic inflammatory pain through TRPA1 activation. Targeting against OxPAPC and TRPA1 signaling pathway may be promising in inflammatory pain treatment. PMID:27812120

  5. Changes in markers of brain serotonin activity in response to chronic exercise in senior men.

    PubMed

    Melancon, Michel O; Lorrain, Dominique; Dionne, Isabelle J

    2014-11-01

    Aging is associated with noticeable impairments in brain serotonin transmission, which might contribute to increased vulnerability to developing depression in later life. Animal and human studies have shown that aerobic exercise can stimulate brain serotonin activity and trigger parallel elevations in tryptophan (TRP, the serotonin precursor) availability in blood plasma. However, the influence of chronic exercise on serotonergic activity in older adults is not yet known. Sixteen men aged 64 ± 3 years exercised for 1 h (67%-70% peak oxygen consumption) at baseline and following 16 weeks of aerobic training. The main outcome measures were cardiorespiratory fitness, body composition, branched-chain amino acids (BCAA), TRP, prolactin, lactate, and free fatty acids (FFA). Changes in plasma free-TRP/BCAA and prolactin served as surrogates for TRP availability and serotonin activity, respectively. Chronic exercise decreased body mass (P < 0.05) whilst it increased ventilatory threshold 2 (P < 0.01). Although training did not affect plasma TRP availability to the brain at rest, both pre- and post-training exercise challenges markedly increased TRP availability (P < 0.001). The free-TRP/BCAA values reached a ceiling during exercise that was lower following training (P < 0.05), whereas similar patterns were found for prolactin, lactate, and FFA. These data show that aerobic exercise elicits consistent transient elevations in plasma TRP availability to the brain in older men; the elevations were independent from physical training, although less pronounced following training. The data support the contention that repeated elevations in brain serotonin activity might be involved in the antidepressant effect of exercise training in older adults.

  6. Sleep active cortical neurons expressing neuronal nitric oxide synthase are active after both acute sleep deprivation and chronic sleep restriction.

    PubMed

    Zielinski, M R; Kim, Y; Karpova, S A; Winston, S; McCarley, R W; Strecker, R E; Gerashchenko, D

    2013-09-05

    Non-rapid eye movement (NREM) sleep electroencephalographic (EEG) delta power (~0.5-4 Hz), also known as slow wave activity (SWA), is typically enhanced after acute sleep deprivation (SD) but not after chronic sleep restriction (CSR). Recently, sleep-active cortical neurons expressing neuronal nitric oxide synthase (nNOS) were identified and associated with enhanced SWA after short acute bouts of SD (i.e., 6h). However, the relationship between cortical nNOS neuronal activity and SWA during CSR is unknown. We compared the activity of cortical neurons expressing nNOS (via c-Fos and nNOS immuno-reactivity, respectively) and sleep in rats in three conditions: (1) after 18-h of acute SD; (2) after five consecutive days of sleep restriction (SR) (18-h SD per day with 6h ad libitum sleep opportunity per day); (3) and time-of-day matched ad libitum sleep controls. Cortical nNOS neuronal activity was enhanced during sleep after both 18-h SD and 5 days of SR treatments compared to control treatments. SWA and NREM sleep delta energy (the product of NREM sleep duration and SWA) were positively correlated with enhanced cortical nNOS neuronal activity after 18-h SD but not 5days of SR. That neurons expressing nNOS were active after longer amounts of acute SD (18h vs. 6h reported in the literature) and were correlated with SWA further suggest that these cells might regulate SWA. However, since these neurons were active after CSR when SWA was not enhanced, these findings suggest that mechanisms downstream of their activation are altered during CSR.

  7. Acute and chronic psychostimulant treatment modulates the diurnal rhythm activity pattern of WKY female adolescent rats.

    PubMed

    Jones, Cathleen G; Yang, Pamela B; Wilcox, Victor T; Burau, Keith D; Dafny, Nachum

    2014-05-01

    The psychostimulants considered the gold standard in the treatment of attention deficit hyperactivity disorder, one of the most common childhood disorders, are also finding their way into the hands of healthy young adults as brain augmentation to improve cognitive performance. The possible long-term effects of psychostimulant exposure in adolescence are considered controversial, and thus, the objective of this study was to investigate whether the chronic exposure to the psychostimulant amphetamine affects the behavioral diurnal rhythm activity patterns of female adolescent Wistar-Kyoto (WKY) rat. The hypothesis of this study is that change in diurnal rhythm activity pattern is an indicator for the long-term effect of the treatment. Twenty-four rats were divided into two groups, control (N = 12) and experimental (N = 12), and kept in a 12:12-h light/dark cycle in an open-field cage. After 5-7 days of acclimation, 11 days of consecutive non-stop behavioral recordings began. On experimental day 1 (ED1), all groups were given an injection of saline. On ED2 to ED7, the experimental group was injected with 0.6 mg/kg amphetamine followed by 3 days of washout from ED8 to ED10, and amphetamine re-challenge on ED11 similar to ED2. The locomotor movements were counted by the computerized animal activity monitoring system, and the cosinor statistical test analysis was used to fit a 24-h curve of the control recording to the activity pattern after treatment. The horizontal activity, total distance, number of stereotypy, vertical activity, and stereotypical movements were analyzed to find out whether the diurnal rhythm activity patterns were altered. Data obtained using these locomotor indices of diurnal rhythm activity pattern suggest that amphetamine treatment significantly modulates the locomotor diurnal rhythm activity pattern of female WKY adolescent rats.

  8. Autoinflammatory granulomatous diseases: from Blau syndrome and early-onset sarcoidosis to NOD2-mediated disease and Crohn's disease

    PubMed Central

    Caso, Francesco; Galozzi, Paola; Costa, Luisa; Sfriso, Paolo; Cantarini, Luca; Punzi, Leonardo

    2015-01-01

    The recent identification of genetic mutations leading to dysfunction of inflammatory and apoptotic pathways, has allowed to characterise a group of diseases, recognised as monogenic autoinflammatory syndromes. Among those, Blau syndrome (BS) and early-onset sarcoidosis (EOS) have been identified as familial and sporadic phenotypes of the same non-caseating granulomatous form. Both the diseases are caused by mutations in the CARD15/NOD2 gene, encoding the cytosolic NOD2 protein, one of the key molecules in the regulation of innate immunity. Clinical onset is typically located in the first years of life and phenotype is characterised by simultaneous or less articular, cutaneous and ocular non-caseating granulomatous inflammation, which can be variably associated with a heterogeneous systemic spectrum. The CARD15/NOD2 gene has also been identified as one of the genes linked to susceptibility to Crohn's disease (CD), a common polygenic inflammatory granulomatous bowel disease. The heightened nuclear factor-κB activity, found in the intestinal tissue of patients affected by CD, has probably a genetic cause related to several CARD15/NOD2 polymorphisms. Other substitutions in the CARD15/NOD2 gene have also been found in a recently described disorder, called NOD2-associated autoinflammatory disease, which shares several clinical characteristics with BS and EOS. This review attempts to describe these diseases on the basis of the most recent evidences. We described genetic and clinical aspects, mainly focusing on BS and EOS, the most representative diseases of autoinflammatory granulomatous diseases, with the ultimate purpose to expand their knowledge. PMID:26509073

  9. Chronic intermittent hypoxia activates nuclear factor-{kappa}B in cardiovascular tissues in vivo

    SciTech Connect

    Greenberg, Harly; Ye Xiaobing; Wilson, David; Htoo, Aung K.; Hendersen, Todd; Liu Shufang . E-mail: sliu@lij.edu

    2006-05-05

    Obstructive sleep apnea (OSA) is an important risk factor for cardiovascular morbidity and mortality. The mechanisms through which OSA promotes the development of cardiovascular disease are poorly understood. In this study, we tested the hypotheses that chronic exposure to intermittent hypoxia and reoxygenation (CIH) is a major pathologic factor causing cardiovascular inflammation, and that CIH-induces cardiovascular inflammation and pathology by activating the NF-{kappa}B pathway. We demonstrated that exposure of mice to CIH activated NF-{kappa}B in cardiovascular tissues, and that OSA patients had markedly elevated monocyte NF-{kappa}B activity, which was significantly decreased when obstructive apneas and their resultant CIH were eliminated by nocturnal CPAP therapy. The elevated NF-{kappa}B activity induced by CIH is accompanied by and temporally correlated to the increased expression of iNOS protein, a putative and important NF-{kappa}B-dependent gene product. Thus, CIH-mediated NF-{kappa}B activation may be a molecular mechanism linking OSA and cardiovascular pathologies seen in OSA patients.

  10. Circadian wheel-running activity during withdrawal from chronic intermittent ethanol exposure in mice

    PubMed Central

    Logan, Ryan W.; Seggio, Joseph A.; Robinson, Stacy L.; Richard, Gregory R.; Rosenwasser, Alan M.

    2010-01-01

    Alcohol withdrawal is associated with affective-behavioral disturbances in both human alcoholics and in animal models. In general, these phenomena are potentiated by increased alcohol exposure duration and by prior withdrawal episodes. Previous studies have also reported locomotor hypoactivity during ethanol withdrawal in rats and mice, but only in novel test environments, not in the home-cage. In the present study, we examined the effects of withdrawal from chronic intermittent ethanol (CIE) vapor exposure on the level and circadian periodicity of wheel-running activity in C57BL/6J mice. CIE treatment resulted in reductions in wheel-running activity relative to plain-air controls that persisted for about one week after withdrawal. Analysis of circadian waveforms indicated that reduced activity occurred throughout the night phase, but that daily activity patterns were otherwise unaltered. CIE failed to alter free-running circadian period or phase in animals maintained under constant darkness. These results show that ethanol withdrawal can result in locomotor hypoactivity even in the habitual, home-cage environment, and suggest that withdrawal-related reductions in wheel-running activity may reflect the specific motivational significance of this behavior. PMID:20682191

  11. Physical Activity on Medical Prescription: A Qualitative Study of Factors Influencing Take-Up and Adherence in Chronically Ill Patients

    ERIC Educational Resources Information Center

    Gasparini, William; Knobé, Sandrine; Didierjean, Romaine

    2015-01-01

    Objective: This study sought to determine the effects of an innovative public health programme offering physical and sports activities on medical prescription to chronically ill patients. Method: Semi-structured interviews were conducted with programme participants at two time points: at the start of their activity (n?=?33) and 3?months after the…

  12. Acute and chronic ethanol exposure differentially alters alcohol dehydrogenase and aldehyde dehydrogenase activity in the zebrafish liver.

    PubMed

    Tran, Steven; Nowicki, Magda; Chatterjee, Diptendu; Gerlai, Robert

    2015-01-02

    Chronic ethanol exposure paradigms have been successfully used in the past to induce behavioral and central nervous system related changes in zebrafish. However, it is currently unknown whether chronic ethanol exposure alters ethanol metabolism in adult zebrafish. In the current study we examine the effect of acute ethanol exposure on adult zebrafish behavioral responses, as well as alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activity in the liver. We then examine how two different chronic ethanol exposure paradigms (continuous and repeated ethanol exposure) alter behavioral responses and liver enzyme activity during a subsequent acute ethanol challenge. Acute ethanol exposure increased locomotor activity in a dose-dependent manner. ADH activity was shown to exhibit an inverted U-shaped curve and ALDH activity was decreased by ethanol exposure at all doses. During the acute ethanol challenge, animals that were continuously housed in ethanol exhibited a significantly reduced locomotor response and increased ADH activity, however, ALDH activity did not change. Zebrafish that were repeatedly exposed to ethanol demonstrated a small but significant attenuation of the locomotor response during the acute ethanol challenge but ADH and ALDH activity was similar to controls. Overall, we identified two different chronic ethanol exposure paradigms that differentially alter behavioral and physiological responses in zebrafish. We speculate that these two paradigms may allow dissociation of central nervous system-related and liver enzyme-dependent ethanol induced changes in zebrafish.

  13. Activated ClpP kills persisters and eradicates a chronic biofilm infection.

    SciTech Connect

    Conlon, Brian P.; Nakayasu, Ernesto S.; Fleck, Laura E.; LaFleur, Michael D.; Isabella, Vincent M.; Coleman, K.; Leonard, Steve N.; Smith, Richard D.; Adkins, Joshua N.; Lewis, Kim

    2013-11-21

    The current antibiotic crisis stems from two distinct phenomena-drug resistance, and drug tolerance. Resistance mechanisms such as drug efflux or modification prevent antibiotics from binding to their targets 1, allowing pathogens to grow. Antibiotic tolerance is the property of persister cells, phenotypic variants of regular bacteria 2. Antibiotics kill by corrupting targets, but these are inactive in dormant persisters, leading to tolerance. Persisters were first identified by Joseph Bigger in 1944, when he discovered a surviving sub-population of Staphylococcus following treatment with penicillin3. Persisters are largely responsible for recalcitrance of chronic diseases such as tuberculosis, and various infections associated with biofilms - endocarditis, osteomyelitis, infections of catheters and indwelling devices, and deep-seated infections of soft tissues 4. There are a number of redundant pathways involved in persister formation5,6 precluding development of drugs inhibiting their formation. The acyldepsipeptide antibiotic (ADEP 4) has been shown to activate the ClpP protease resulting in death of growing cells 7. Here we show that ADEP4 activated ClpP becomes a fairly non-specific protease and kills persister cells by degradation of over 400 intracellular targets. clpP mutants are resistant to ADEP4 7, but we find that they display increased susceptibility to killing by a range of conventional antibiotics. Combining ADEP4 with rifampicin leads to eradication of persisters, stationary and biofilm populations of Staphylococcus aureus in vitro and in a deep-seated murine infection. Target corruption/activation provides an approach to killing persisters and eradicating chronic infections.

  14. Platelet function and activation in Cavalier King Charles Spaniels with subclinical chronic valvular heart disease.

    PubMed

    Tong, Linda J; Hosgood, Giselle L; French, Anne T; Irwin, Peter J; Shiel, Robert E

    2016-08-01

    OBJECTIVE To assess platelet closure time (CT), mean platelet component (MPC) concentration, and platelet component distribution width (PCDW) in dogs with subclinical chronic valvular heart disease. ANIMALS 89 Cavalier King Charles Spaniels (CKCSs) and 39 control dogs (not CKCSs). PROCEDURES Platelet count, MPC concentration, PCDW, and Hct were measured by use of a hematology analyzer, and CT was measured by use of a platelet function analyzer. Murmur grade and echocardiographic variables (mitral valve regurgitant jet size relative to left atrial area, left atrial-to-aortic diameter ratio, and left ventricular internal dimensions) were recorded. Associations between explanatory variables (sex, age, murmur grade, echocardiographic variables, platelet count, and Hct) and outcomes (CT, MPC concentration, and PCDW) were examined by use of multivariate regression models. RESULTS A model with 5 variables best explained variation in CT (R(2), 0.74), with > 60% of the variance of CT explained by mitral valve regurgitant jet size. The model of best fit to explain variation in MPC concentration included only platelet count (R(2), 0.24). The model of best fit to explain variation in PCDW included platelet count and sex (R(2), 0.25). CONCLUSIONS AND CLINICAL RELEVANCE In this study, a significant effect of mitral valve regurgitant jet size on CT was consistent with platelet dysfunction. However, platelet activation, as assessed on the basis of the MPC concentration and PCDW, was not a feature of subclinical chronic valvular heart disease in CKCSs.

  15. Activity of erdosteine on mucociliary transport in patients affected by chronic bronchitis.

    PubMed

    Olivieri, D; Del Donno, M; Casalini, A; D'Ippolito, R; Fregnan, G B

    1991-01-01

    The influence of erdosteine (a mucomodulator endowed with mucolytic and antioxidant properties) on human mucociliary transport (MCT) was investigated in a double-blind placebo controlled study. Sixteen former smokers affected by chronic bronchitis, preselected for their mucociliary responsiveness to an inhaled beta 2-agonist, were divided into two groups (matched by number, sex, age and FEV1%) and orally treated with placebo or erdosteine (300 mg t.i.d.) for 8 days. Their MCT was assessed by the bronchofiberscopy technique just before starting the treatment and at the end of the treatment. The pretreatment mucus transport velocity in these patients was significantly decreased with respect to healthy subjects. The erdosteine treatment induced a significant improvement of MCT while placebo was inactive (mean % variation +/- SE against their baseline values being +60.4 +/- 18.4 and -3.0 +/- 5.9, respectively). This peculiar activity of erdosteine on mucus transport may be of clinical usefulness in chronic bronchitic patients and it can be added to beta 2-agonist to restore the decreased MCT.

  16. IL-10-dependent Tr1 cells attenuate astrocyte activation and ameliorate chronic central nervous system inflammation

    PubMed Central

    Mayo, Lior; Cunha, Andre Pires Da; Madi, Asaf; Beynon, Vanessa; Yang, Zhiping; Alvarez, Jorge I.; Prat, Alexandre; Sobel, Raymond A.; Kobzik, Lester; Lassmann, Hans; Quintana, Francisco J.

    2016-01-01

    See Winger and Zamvil (doi:10.1093/brain/aww121) for a scientific commentary on this article. The innate immune system plays a central role in the chronic central nervous system inflammation that drives neurological disability in progressive forms of multiple sclerosis, for which there are no effective treatments. The mucosal immune system is a unique tolerogenic organ that provides a physiological approach for the induction of regulatory T cells. Here we report that nasal administration of CD3-specific antibody ameliorates disease in a progressive animal model of multiple sclerosis. This effect is IL-10-dependent and is mediated by the induction of regulatory T cells that share a similar transcriptional profile to Tr1 regulatory cells and that suppress the astrocyte inflammatory transcriptional program. Treatment results in an attenuated inflammatory milieu in the central nervous system, decreased microglia activation, reduced recruitment of peripheral monocytes, stabilization of the blood–brain barrier and less neurodegeneration. These findings suggest a new therapeutic approach for the treatment of progressive forms of multiple sclerosis and potentially other types of chronic central nervous system inflammation. PMID:27246324

  17. Improved FRET Biosensor for the Measurement of BCR-ABL Activity in Chronic Myeloid Leukemia Cells.

    PubMed

    Horiguchi, Mika; Fujioka, Mari; Kondo, Takeshi; Fujioka, Yoichiro; Li, Xinxin; Horiuchi, Kosui; O Satoh, Aya; Nepal, Prabha; Nishide, Shinya; Nanbo, Asuka; Teshima, Takanori; Ohba, Yusuke

    2017-02-02

    Although the co-development of companion diagnostics with molecular targeted drugs is desirable, truly efficient diagnostics are limited to diseases in which chromosomal translocations or overt mutations are clearly correlated with drug efficacy. Moreover, even for such diseases, few methods are available to predict whether drug administration is effective for each individual patient whose disease is expected to respond to the drug(s). We have previously developed a biosensor based on the principle of Förster resonance energy transfer to measure the activity of the tyrosine kinase BCR-ABL and its response to drug treatment in patient-derived chronic myeloid leukemia cells. The biosensor harbors CrkL, one of the major substrates of BCR-ABL, and is therefore named Pickles after phosphorylation indicator of CrkL en substrate. The efficacy of this technique as a clinical test has been demonstrated, but the number of cells available for analysis is limited in a case-dependent manner, owing to the cleavage of the biosensor in patient-derived leukemia cells. Here, we describe an improved biosensor with an amino acid substitution and a nuclear export signal being introduced. Of the two predicted cleavage positions in CrkL, the mutations inhibited one cleavage completely and the other cleavage partially, thus collectively increasing the number of cells available for drug evaluation. This improved version of the biosensor holds promise in the future development of companion diagnostics to predict responses to tyrosine kinase inhibitors in patients with chronic myeloid leukemia.

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

    PubMed Central

    Kiernan, Elizabeth A.; Smith, Stephanie M. C.; Mitchell, Gordon S.

    2016-01-01

    Abstract Chronic intermittent hypoxia (CIH) is a hallmark of sleep apnoea, a condition associated with diverse clinical disorders. CIH and sleep apnoea are characterized by increased reactive oxygen species formation, peripheral and CNS inflammation, neuronal death and neurocognitive deficits. Few studies have examined the role of microglia, the resident CNS immune cells, in models of CIH. Thus, little is known concerning their direct contributions to neuropathology or the cellular mechanisms regulating their activities during or following pathological CIH. In this review, we identify gaps in knowledge regarding CIH‐induced microglial activation, and propose mechanisms based on data from related models of hypoxia and/or hypoxia–reoxygenation. CIH may directly affect microglia, or may have indirect effects via the periphery or other CNS cells. Peripheral inflammation may indirectly activate microglia via entry of pro‐inflammatory molecules into the CNS, and/or activation of vagal afferents that trigger CNS inflammation. CIH‐induced release of damage‐associated molecular patterns from injured CNS cells may also activate microglia via interactions with pattern recognition receptors expressed on microglia. For example, Toll‐like receptors activate mitogen‐activated protein kinase/transcription factor pathways required for microglial inflammatory gene expression. Although epigenetic effects from CIH have not yet been studied in microglia, potential epigenetic mechanisms in microglial regulation are discussed, including microRNAs, histone modifications and DNA methylation. Epigenetic effects can occur during CIH, or long after it has ended. A better understanding of CIH effects on microglial activities may be important to reverse CIH‐induced neuropathology in patients with sleep disordered breathing. PMID:26890698

  19. Chronic imaging of movement-related Purkinje cell calcium activity in awake behaving mice

    PubMed Central

    Gaffield, Michael A.; Amat, Samantha B.; Bito, Haruhiko

    2015-01-01

    Purkinje cells (PCs) are a major site of information integration and plasticity in the cerebellum, a brain region involved in motor task refinement. Thus PCs provide an ideal location for studying the mechanisms necessary for cerebellum-dependent motor learning. Increasingly, sophisticated behavior tasks, used in combination with genetic reporters and effectors of activity, have opened up the possibility of studying cerebellar circuits during voluntary movement at an unprecedented level of quantitation. However, current methods used to monitor PC activity do not take full advantage of these advances. For example, single-unit or multiunit electrode recordings, which provide excellent temporal information regarding electrical activity, only monitor a small population of cells and can be quite invasive. Bolus loading of cell-permeant calcium (Ca2+) indicators is short-lived, requiring same-day imaging immediately after surgery and/or indicator injection. Genetically encoded Ca2+ indicators (GECIs) overcome many of these limits and have garnered considerable use in many neuron types but only limited use in PCs. Here we employed these indicators to monitor Ca2+ activity in PCs over several weeks. We could repeatedly image from the same cerebellar regions across multiple days and observed stable activity. We used chronic imaging to monitor PC activity in crus II, an area previously linked to licking behavior, and identified a region of increased activity at the onset of licking. We then monitored this same region after training tasks to initiate voluntary licking behavior in response to different sensory stimuli. In all cases, PC Ca2+ activity increased at the onset of rhythmic licking. PMID:26561609

  20. Chronic Low Back Pain in Women: Muscle Activation during Task Performance

    PubMed Central

    Santos, Fernanda G; Carmo, Carolina M; Fracini, América C; Pereira, Rita R P; Takara, Kelly S; Tanaka, Clarice

    2014-01-01

    [Purpose] The aim of this study was to compare the activities of the trunk and hip muscles in chronic low back pain (CLBP) women and asymptomatic subjects during the kneeling to half-kneeling task. [Subjects] Twenty-nine CLBP women and thirty asymptomatic subjects (C) participated in this study. [Methods] Electromyography activity (EMG) of the obliquus internus abdominis (OI), the lumbar erector spinae (LES) and the gluteus medius (GM) muscles was recorded bilaterally. The peak amplitude, the time of peak amplitude and the integrated linear envelope EMG for each muscle were obtained. [Results] The C group bilateral OI and GM muscles displayed higher peak amplitudes and earlier times of peak amplitude. They also had higher integrated linear envelope EMG values. The CLBP group bilateral LES muscles had higher peak amplitudes and earlier times of peak amplitude. They also showed an increased integrated linear envelope EMG values. [Conclusion] The CLBP women activate the LES muscles in the kneeling to half-kneeling task, showing different patterns of motor planning activity. PMID:24409022

  1. Behavioral responses of high and low active male rats to the chronic ingestion of desipramine.

    PubMed

    Echandía, E L; Broitman, S T; Fóscolo, M R

    1985-06-01

    Male rats arbitrarily selected for high and low motor activity (HA and LA-rats) were submitted to the chronic ingestion (30 days) of desipramine (DSP) in doses of about 1.5, 3 and 6 mg/kg/24 hr. Their motor activity was assessed in an animal activity monitor providing a measure of total horizontal movements and vertical movements and in a hole-board providing a measure of locomotion, head-dipping and grooming. There were significant differences between HA and LA-rats in their behavioral response to DSP treatment. At the doses used DSP did not affect horizontal and vertical movements and hole-board locomotion or exploration in HA-rats (Experiment 1). In LA-rats, however (Experiment 2), these motor activities were significantly stimulated by DSP. Such effect was dose dependent; 1.5 mg/kg/24 hr was ineffective while 6 mg/kg/24 hr produced a clear cut reversion of hypoactivity. It is speculated that DSP treatment increased resistance of LA-rats to the mild stress caused by testing.

  2. Chronic ethanol intake modifies renin-angiotensin system-regulating aminopeptidase activities in mouse cerebellum.

    PubMed

    Mayas, M D; Ramírez-Expósito, M J; García, M J; Carrera, M P; Cobo, M; Camacho, B; Martínez Martos, J M

    2005-04-01

    In developing cerebellum, where critical periods of vulnerability have been established for several basic substances, it has been extensively studied the wide array of abnormalities induced by exposure to ethanol (EtOH). However, little is known about the effects of EtOH consumption on cerebellar functions in adult individuals. Several studies show participation in cognitive activities to be concentrated in the lateral cerebellum (hemispheres), whereas basic motor functions such as balance and coordination are represented in the medial parts of the cerebellum (vermis and paravermis). In addition to the circulating renin angiotensin system (RAS), a local system has been postulated in brain. The effector peptides of the RAS are formed via the activity of several aminopeptidases (AP). The present work analyses the effect of chronic EtOH intake on the RAS-regulating AP activities in the soluble and membrane-bound fractions of two cerebellar locations: the hemispheres and the vermis. We hypothesize that cerebellar RAS is involved in basic motor functions rather than in cognitive activities.

  3. Comparison of Salivary Beta Glucuronidase Activity in Chronic Periodontitis Patients with and without Diabetes Mellitus

    PubMed Central

    ND, Jayakumar; Varghese, Sheeja

    2014-01-01

    Aim of the study: The aim of the study was to estimate the salivary beta glucuronidase (β) activity in patients with chronic periodontitis with and without diabetes mellitus and to evaluate the relationship between Beta Glucuronidase activity and Periodontal clinical parameters. Materials and Methods: The study consisted of 80 patients of both sexes with age ranging from 20-60 years and they were divided into four groups. Clinical parameters such as Gingival index, Probing depth and Clinical attachment loss were measured. Salivary Beta Glucuronidase activity was measured using spectrophotometer with reagents like phenolphthalein glucuronic acid, phosphate and glycine buffer. Results: The mean BG activity of Group IV (1.17 ± 0.27) was significantly higher than mean BGA levels of Group I, II, III. The p-value was < 0.05. The mean BGA levels of Group III (0.78 ± 0.17) was significantly higher than mean BGA levels of Group I, Group II at 5 % level. There was a significant positive linear relationship between salivary β Glucuronidase level and Probing Depth, clinical attachment level in the experimental Groups. Conclusion: The salivary β Glucuronidase level was higher in Diabetic patients with periodontitis than nondiabetic periodontitis patients. PMID:25121058

  4. In Situ Anabolic Activity of Periodontal Pathogens Porphyromonas gingivalis and Filifactor alocis in Chronic Periodontitis

    PubMed Central

    Spooner, Ralee; Weigel, Kris M.; Harrison, Peter L.; Lee, KyuLim; Cangelosi, Gerard A.; Yilmaz, Özlem

    2016-01-01

    Porphyromonas gingivalis and Filifactor alocis are fastidious anaerobic bacteria strongly associated with chronic forms of periodontitis. Our understanding of the growth activities of these microorganisms in situ is very limited. Previous studies have shown that copy numbers of ribosomal-RNA precursor (pre-rRNA) of specific pathogen species relative to genomic-DNA (gDNA) of the same species (P:G ratios) are greater in actively growing bacterial cells than in resting cells. The method, so-called steady-state pre-rRNA-analysis, represents a novel culture-independent approach to study bacteria. This study employed this technique to examine the in situ growth activities of oral bacteria in periodontitis before and after non-surgical periodontal therapy. Sub-gingival paper-point samples were taken at initial and re-evaluation appointments. Pre-rRNA and gDNA levels of P. gingivalis and F. alocis were quantified and compared using reverse-transcriptase qPCR. The results indicate significantly reduced growth activity of P. gingivalis, but not F. alocis, after therapy. The P:G ratios of P. gingivalis and F. alocis were compared and a low-strength, but statistically significant inter-species correlation was detected. Our study demonstrates that steady-state pre-rRNA-analysis can be a valuable culture-independent approach to studying opportunistic bacteria in periodontitis. PMID:27642101

  5. Low putamen activity associated with poor reward sensitivity in childhood chronic fatigue syndrome.

    PubMed

    Mizuno, Kei; Kawatani, Junko; Tajima, Kanako; Sasaki, Akihiro T; Yoneda, Tetsuya; Komi, Masanori; Hirai, Toshinori; Tomoda, Akemi; Joudoi, Takako; Watanabe, Yasuyoshi

    2016-01-01

    Motivational signals influence a wide variety of cognitive processes and components of behavioral performance. Cognitive dysfunction in patients with childhood chronic fatigue syndrome (CCFS) may be closely associated with a low motivation to learn induced by impaired neural reward processing. However, the extent to which reward processing is impaired in CCFS patients is unclear. The aim of the present functional magnetic resonance imaging (fMRI) study was to determine whether brain activity in regions related to reward sensitivity is impaired in CCFS patients. fMRI data were collected from 13 CCFS patients (mean age, 13.6 ± 1.0 years) and 13 healthy children and adolescents (HCA) (mean age, 13.7 ± 1.3 years) performing a monetary reward task. Neural activity in high- and low-monetary-reward conditions was compared between CCFS and HCA groups. Severity of fatigue and the reward obtained from learning in daily life were evaluated by questionnaires. Activity of the putamen was lower in the CCFS group than in the HCA group in the low-reward condition, but not in the high-reward condition. Activity of the putamen in the low-reward condition in CCFS patients was negatively and positively correlated with severity of fatigue and the reward from learning in daily life, respectively. We previously revealed that motivation to learn was correlated with striatal activity, particularly the neural activity in the putamen. This suggests that in CCFS patients low putamen activity, associated with altered dopaminergic function, decreases reward sensitivity and lowers motivation to learn.

  6. Patient's Perception of Symptoms Related to Morning Activity in Chronic Obstructive Pulmonary Disease: The SYMBOL Study

    PubMed Central

    Kim, Yeon Jae; Lee, Byung Ki; Jung, Chi Young; Jeon, Young June; Hyun, Dae Sung; Kim, Kyung Chan; Yu, Sung Ken; Choi, Hye Sook; Shin, Won Hyuk

    2012-01-01

    Background/Aims Patients with chronic obstructive pulmonary disease (COPD) experience more problematic respiratory symptoms and have more trouble performing daily activities in the morning. The aim of this study was to assess the perception of COPD symptoms related to morning activities in patients with severe airflow limitation. Methods Data of 133 patients with severe airflow limitation were analyzed in a prospective, non-interventional study. A clinical symptom questionnaire was completed by patients at baseline. In patients having morning symptoms, defined by at least one or more prominent or aggravating symptom during morning activities, a morning activity questionnaire was also completed at baseline and following 2 months of COPD treatment. Results The most frequently reported COPD symptom was breathlessness (90.8%). Morning symptoms were reported in 76 (57%) patients; these had more frequent and severe clinical COPD symptoms. The most frequently reported morning activity was getting out of bed (82.9%). The long acting muscarinic antagonist (odds ratio [OR], 6.971; 95% confidence interval [CI], 1.317 to 11.905) and chest tightness (OR, 0.075; 95% CI, 0.011 to 0.518) were identified as significantly related to absence of morning symptoms. There was no significant correlation between the degree of forced expiratory volume in 1 second improvement and severity score differences of all items of morning activity after 2-month treatment. Conclusions Fifty-seven percent of COPD patients with severe airflow limitation have morning symptoms that limit their morning activities. These patients also have more prevalent and severe COPD symptoms. The results of this study therefore provide valuable information for the development of patient-reported outcomes in COPD. PMID:23269884

  7. Toll-like receptor 4 contributes to chronic itch, alloknesis and spinal astrocyte activation in male mice

    PubMed Central

    Liu, Tong; Han, Qingjian; Chen, Gang; Huang, Ya; Zhao, Lin-Xia; Berta, Temugin; Gao, Yong-Jing; Ji, Ru-Rong

    2016-01-01

    Increasing evidence suggests that Toll-like receptor 4 (TLR4) contributes importantly to spinal cord glial activation and chronic pain sensitization; however, its unique role in acute and chronic itch is unclear. In this study, we investigated the involvement of TLR4 in acute and chronic itch models in male mice using both transgenic and pharmacological approaches. Tlr4−/− mice exhibited normal acute itch induced by compound 48/80 and chloroquine, but these mice showed substantial reductions in scratching in chronic itch models of dry skin, induced by acetone and diethyether followed by water (AEW), contact dermatitis, and allergic contact dermatitis on the neck. Intrathecal (spinal) inhibition of TLR4 with lipopolysaccharide Rhodobacter sphaeroides (LPS-RS) did not affect acute itch but suppressed AEW-induced chronic itch. Compound 48/80 and AEW also produced robust alloknesis, a touch-elicited itch in wild-type mice, which was suppressed by intrathecal LPS-RS and Tlr4−/− deletion. AEW induced persistent upregulation of Tlr4 mRNA and increased TLR4 expression in GFAP-expressing astrocytes in spinal cord dorsal horn. AEW also induced TLR4-dependent astrogliosis (GFAP upregulation) in spinal cord. Intrathecal injection of astroglial inhibitor L-α-aminoadipate reduced AEW-induced chronic itch and alloknesis without affecting acute itch. Spinal TLR4 was also necessary for AEW-induced chronic itch in the cheek model. Interestingly, scratching plays an essential role in spinal astrogliosis, since AEW-induced astrogliosis was abrogated by putting Elizabethan Collars on the neck to prevent scratching the itchy skin. Our findings suggest that spinal TLR4 signaling is important for spinal astrocyte activation and astrogliosis that may underlie alloknesis and chronic itch. PMID:26645545

  8. Toll-like receptor 4 contributes to chronic itch, alloknesis, and spinal astrocyte activation in male mice.

    PubMed

    Liu, Tong; Han, Qingjian; Chen, Gang; Huang, Ya; Zhao, Lin-Xia; Berta, Temugin; Gao, Yong-Jing; Ji, Ru-Rong

    2016-04-01

    Increasing evidence suggests that Toll-like receptor 4 (TLR4) contributes importantly to spinal cord glial activation and chronic pain sensitization; however, its unique role in acute and chronic itch is unclear. In this study, we investigated the involvement of TLR4 in acute and chronic itch models in male mice using both transgenic and pharmacological approaches. Tlr4 mice exhibited normal acute itch induced by compound 48/80 and chloroquine, but these mice showed substantial reductions in scratching in chronic itch models of dry skin, induced by acetone and diethylether followed by water (AEW), contact dermatitis, and allergic contact dermatitis on the neck. Intrathecal (spinal) inhibition of TLR4 with lipopolysaccharide Rhodobacter sphaeroides did not affect acute itch but suppressed AEW-induced chronic itch. Compound 48/80 and AEW also produced robust alloknesis, a touch-elicited itch in wild-type mice, which was suppressed by intrathecal lipopolysaccharide R sphaeroides and Tlr4 deletion. Acetone and diethylether followed by water induced persistent upregulation of Tlr4 mRNA and increased TLR4 expression in GFAP-expressing astrocytes in spinal cord dorsal horn. Acetone and diethylether followed by water also induced TLR4-dependent astrogliosis (GFAP upregulation) in spinal cord. Intrathecal injection of astroglial inhibitor L-α-aminoadipate reduced AEW-induced chronic itch and alloknesis without affecting acute itch. Spinal TLR4 was also necessary for AEW-induced chronic itch in the cheek model. Interestingly, scratching plays an essential role in spinal astrogliosis because AEW-induced astrogliosis was abrogated by putting Elizabethan collars on the neck to prevent scratching the itchy skin. Our findings suggest that spinal TLR4 signaling is important for spinal astrocyte activation and astrogliosis that may underlie alloknesis and chronic itch.

  9. Mechanistic insights on immunosenescence and chronic immune activation in HIV-tuberculosis co-infection

    PubMed Central

    Shankar, Esaki M; Velu, Vijayakumar; Kamarulzaman, Adeeba; Larsson, Marie

    2015-01-01

    Immunosenescence is marked by accelerated degradation of host immune responses leading to the onset of opportunistic infections, where senescent T cells show remarkably higher ontogenic defects as compared to healthy T cells. The mechanistic association between T-cell immunosenescence and human immunodeficiency virus (HIV) disease progression, and functional T-cell responses in HIV-tuberculosis (HIV-TB) co-infection remains to be elaborately discussed. Here, we discussed the association of immunosenescence and chronic immune activation in HIV-TB co-infection and reviewed the role played by mediators of immune deterioration in HIV-TB co-infection necessitating the importance of designing therapeutic strategies against HIV disease progression and pathogenesis. PMID:25674514

  10. Randomised controlled trial of lymphoblastoid interferon for chronic active hepatitis B.

    PubMed Central

    Anderson, M G; Harrison, T J; Alexander, G; Zuckerman, A J; Murray-Lyon, I M

    1987-01-01

    Thirty male patients (27 homosexual) with biopsy proven chronic active hepatitis B were randomised to receive lymphoblastoid interferon (Wellferon) or no treatment. All patients were HBeAg positive and had continuing viral replication. Patients receiving treatment were given a single daily intramuscular injection of interferon for 28 days at a starting dose of 2.5 MU/m2 increasing to a maximum of 7.5 MU/m2/day. Transient side effects of malaise and influenza like symptoms occurred in all patients and resolved rapidly after treatment. Hepatitis B viral replication was suppressed during interferon treatment in all patients but the effect was limited to the period of therapy. After one year there was no appreciable difference in viral markers between the two groups of patients and this treatment schedule appears less effective than the thrice weekly, three month regimes recently reported from other centres. PMID:3297940

  11. Calcium-sensing receptor activation in chronic kidney disease: effects beyond parathyroid hormone control.

    PubMed

    Massy, Ziad A; Hénaut, Lucie; Larsson, Tobias E; Vervloet, Marc G

    2014-11-01

    Secondary hyperparathyroidism (SHPT) is an important complication of advanced chronic kidney disease (CKD). Cinacalcet, an allosteric modulator of the calcium-sensing receptor (CaSR) expressed in parathyroid glands, is the only calcimimetic approved to treat SHPT in patients on dialysis. By enhancing CaSR sensitivity for plasma extracellular calcium (Ca(2+)0), cinacalcet reduces serum parathyroid hormone, Ca(2+)0, and serum inorganic phosphorous concentrations, allowing better control of SHPT and CKD-mineral and bone disorders. Of interest, the CaSR also is expressed in a variety of tissues where its activation regulates diverse cellular processes, including secretion, apoptosis, and proliferation. Thus, the existence of potential off-target effects of cinacalcet cannot be neglected. This review summarizes our current knowledge concerning the potential role(s) of the CaSR expressed in various tissues in CKD-related disorders, independently of parathyroid hormone control.

  12. Studies on the Pathogenesis of Experimental Chronic Active Hepatitis in Rabbits

    PubMed Central

    Hopf, U.; Meyer zum Büschenfelde, K.-H.

    1974-01-01

    Isolated hepatocytes of rabbits with experimentally induced chronic active hepatitis (CAH) in different stages and liver cirrhosis, respectively, and of animals without liver lesions were studied by immunofluorescence with regard to surface bound immunoglobulin. In 8 of 9 animals with CAH immunoglobulin could be demonstrated on the membranes of the hepatocytes. One animal with liver cirrhosis did not show fixed gammaglobulin; 8 animals without liver lesions which had been immunized with xenogeneic (human) together with allogeneic liver specific proteins (RLP) had no immunoglobulin bound to their hepatocytes, with one exception. The antibody titres in the serum of these animals against liver specific proteins (passive haemagglutination and gel diffusion) were not different from those in animals with liver lesions. The skin test reactivity with RLP as antigen corresponded largely to the development of liver lesions. The pathogenic importance of an antibody mediated lymphocytic cytotoxicity for the induction of CAH is discussed. ImagesFig. PMID:4217635

  13. Signal Transducer and Activator of Transcription (STAT)-3 Activates Nuclear Factor (NF)-κB in Chronic Lymphocytic Leukemia Cells

    PubMed Central

    Liu, Zhiming; Hazan-Halevy, Inbal; Harris, David M.; Li, Ping; Ferrajoli, Alessandra; Faderl, Stefan; Keating, Michael J.; Estrov, Zeev

    2014-01-01

    Nuclear factor (NF)-κB plays a major role in the pathogenesis of B-cell neoplasms. A broad array of mostly extracellular stimuli has been reported to activate NF-κB, to various degrees, in chronic lymphocytic leukemia (CLL) cells. Because CLL cells harbor high levels of unphosphorylated (U) signal transducer and activator of transcription (STAT)-3 protein and U-STAT3 was reported to activate NF-κB, we sought to determine whether U-STAT3 activates NF-κB in CLL. Using the electrophoretic mobility shift assay (EMSA) we studied peripheral blood low-density cells from 15 patients with CLL and found that CLL cell nuclear extracts from all the samples bound to an NF-κB DNA probe, suggesting that NF-κB is constitutively activated in CLL. Immunoprecipitation studies showed that STAT3 bound NF-κB p65, and confocal microscopy studies detected U-STAT3/NF-κB complexes in the nuclei of CLL cells, thereby confirming these findings. Furthermore, infection of CLL cells with retroviral STAT3-shRNA attenuated the binding of NF-κB to DNA, as assessed by EMSA, and downregulated mRNA levels of NF-κB-regulated genes, as assessed by quantitative polymerase chain reaction. Taken together, our data suggest that U-STAT3 binds to the NF-κB p50/p65 dimers and that the U-STAT3/NF-κB complexes bind to DNA and activate NF-κB-regulated genes in CLL cells. PMID:21364020

  14. Associations between early life experience, chronic HPA axis activity, and adult social rank in rhesus monkeys.

    PubMed

    Dettmer, Amanda M; Wooddell, Lauren J; Rosenberg, Kendra L; Kaburu, Stefano S K; Novak, Melinda A; Meyer, Jerrold S; Suomi, Stephen J

    2017-02-01

    Early life experience and socioeconomic status (SES) are well-established predictors of health outcomes in people. Both factors likely influence health outcomes via hypothalamic-pituitary-adrenal (HPA) axis regulation. However, it is unclear how early experience and HPA axis activity influence adult social status. We studied differentially reared female rhesus monkeys (Macaca mulatta, N = 90) as models to test the hypothesis that chronic HPA axis activity assessed via hair cortisol concentrations (HCCs) mediated the relationship between early life experience and adult social rank. We found that mother-peer-reared (MPR) monkeys acquired higher social ranks than either of the two nursery-reared (NR) groups (peer-reared, PR, or surrogate-peer-reared, SPR monkeys) (β = -0.07, t(89) = -2.16, p = 0.034). We also found that MPR HCCs were lower during the juvenile period at 18 months (F(2,25) = 3.49, p = 0.047). Furthermore, for MPR but not NR monkeys, changes in HCCs from 18 to 24 months (r(s) = -0.627, p = 0.039) and adult HCCs (r(s) = -0.321, p = 0.03) were negatively correlated with adult social rank. These findings suggest that chronic HPA axis regulation in juvenility, and perhaps in adulthood, may influence adult social status for primates that experience typical early rearing. However, early life adversity may result in dissociation between neuroendocrine stress regulation and adult social competence, which may be risk factors for adverse health outcomes.

  15. Antibodies to liver membrane antigens in chronic active hepatitis (CAH). II. Specificity for autoimmune CAH.

    PubMed Central

    Frazer, I H; Kronborg, I J; Mackay, I R

    1983-01-01

    An immunoradiometric assay for IgG class autoantibody to liver membrane antigens, based on serum binding to glutaraldehyde treated monkey hepatocytes, was used to examine sera from patients with chronic active hepatitis (CAH) and other acute and chronic liver diseases. All sera from normals and patients showed binding, up to a titre of 1/2,048. For comparison of assays, results were normalized by selecting two reference sera, one with a high degree of binding, and one from a healthy subject with a low degree of binding: at a dilution of 1/2,048, these sera were given binding values of 100% and 0%. The values for the binding of unknown sera at the same dilution were calculated from these two reference values. For 26 patients with autoimmune CAH, the mean (+/- s.d.) percentage binding value (70 +/- 33%) was significantly higher than the mean value for 26 healthy subjects (10 +/- 15%), and high binding values were significantly associated with biochemically active hepatitis. The mean percentage binding value was moderately increased for eight patients with HBsAg associated CAH (42 +/- 12%), 13 patients with alcoholic hepatitis with cirrhosis (37 +/- 25%) and 45 patients with acute viral hepatitis A (40 +/- 27%) or B (52 +/- 37%). At a cut-off binding value of 65%, the assay as a single diagnostic procedure was shown to have a 70% sensitivity and a 95% specificity for the diagnosis of autoimmune CAH. Better understanding of the pathogenetic significance of antibodies to liver membrane antigens in CAH and other liver diseases will depend upon biochemical analysis of the presumably multiple antigenic determinants on the hepatocyte membrane. PMID:6616969

  16. Assessment of neuromuscular and haemodynamic activity in individuals with and without chronic low back pain

    PubMed Central

    McKeon, Melissa D; Albert, Wayne J; Neary, J Patrick

    2006-01-01

    Background Biering-Sørenson (1984) found that individuals with less lumbar extensor muscle endurance had an increased occurrence of first episode low back pain. As a result, back endurance tests have been recommended for inclusion in health assessment protocols. However, different studies have reported markedly different values for endurance times, leading some researchers to believe that the back is receiving support from the biceps femoris and gluteus maximus. Therefore, this study was designed to examine the haemodynamic and neuromuscular activity of the erector spinae, biceps femoris, and gluteus maximus musculature during the Biering-Sørenson Muscular Endurance Test (BSME). Methods Seventeen healthy individuals and 46 individuals with chronic low back pain performed the Biering-Sørenson Muscular Endurance Test while surface electromyography was used to quantify neuromuscular activity. Disposable silver-silver-chloride electrodes were placed in a bipolar arrangement over the right or left biceps femoris, gluteus maximus, and the lumbosacral paraspinal muscles at the level of L3. Near Infrared Spectroscopy was used simultaneously to measure tissue oxygenation and blood volume changes of the erector spinae and biceps femoris. Results The healthy group displayed a significantly longer time to fatigue (Healthy: 168.5s, LBP: 111.1s; p ≤ 0.05). Significant differences were shown in the median frequency slope of the erector spinae between the two groups at 90–100% of the time to fatigue while no significant differences were noted in the haemodynamic data for the two groups. Conclusion Although the BSME has been recognized as a test for back endurance, individuals with chronic LBP appear to incorporate a strategy that may help support the back musculature by utilizing the biceps femoris and gluteus maximus to a greater degree than their healthy counterparts. PMID:16734915

  17. Hypercalcemia, Anemia, and Acute Kidney Injury: A Rare Presentation of Sarcoidosis

    PubMed Central

    Sharma, Neeraj; Tariq, Hassan; Uday, Kalpana; Skaradinskiy, Yevgeniy; Niazi, Masooma; Chilimuri, Sridhar

    2015-01-01

    We discuss a case of a 61-year-old woman who presented with substernal chest pain. She was found to have elevated calcium levels, anemia, and acute kidney injury. The hypercalcemia persisted despite therapy with fluids and bisphosphonates. She was found to have nonparathyroid hormone (PTH) mediated hypercalcemia. The chest X-ray did not reveal any pathology. Our Initial impression was likely underlying hematologic malignancy such as lymphoma or multiple myeloma. A bone marrow biopsy was performed that revealed nonnecrotizing granulomatous inflammation. Further workup revealed elevated vitamin 1,25 dihydroxy level, beta-two microglobulin level, and ACE levels. Noncontrast computed tomography (CT) scan of chest showed bilateral apical bronchiectasis, but did not show any lymphadenopathy or evidence of malignancy. Subsequently, a fiber optic bronchoscopy with transbronchial biopsy showed nonnecrotizing granulomatous inflammation consistent with sarcoidosis. After initiating glucocorticoid therapy, the patient's hypercalcemia improved and her kidney function returned to baseline. PMID:26199627

  18. Differential Expression of Cardiac Troponin T and I in a Patient with Isolated Skeletal Muscular Sarcoidosis

    PubMed Central

    Mannoji, Hiroshi; Hayashi, Fumie; Kubota, Toru; Ikeda, Yoshihiko; Ishibashi-Ueda, Hatsue; Kato, Seiya; Tahara, Nobuhiro; Fukutomi, Takayoshi; Yamada, Takeshi; Okabe, Masanori; Yamamoto, Yusuke

    2016-01-01

    A 49-year-old female was referred to our hospital due to high serum creatine kinase (CK) (2,605 IU/L) and serum cardiac troponin T (cTnT) (0.342 ng/mL) levels. She had no other complaints and further examinations suggested no signs of cardiac disease. Additionally, the serum cardiac troponin I (cTnI) levels were normal. She reported having gradually felt difficulty in walking upstairs. A biopsy indicated skeletal muscle sarcoidosis with positive staining for cTnT. Steroid therapy immediately resolved her muscular symptoms with a normalization of the serum CK levels. Since the serum levels of cTnI were normal, the concomitant measurement of cTnT/cTnI might be useful to diagnose skeletal muscular disease biochemically in such cases. PMID:27803423

  19. The anti-arrhythmic effects of prednisone in patients with sarcoidosis.

    PubMed

    Mohsen, Amr

    2011-12-01

    Atrial fibrillation (AF) affects 2.3 million people in the United States and is currently the most common cardiac arrhythmia. Its overall prevalence is only increasing as the population ages. The classical risk factors for developing AF include hypertension, valvular disease, ischemic cardiomyopathy, and thyroid disease. In some patients with AF, an underlying cardiovascular pathology is not identified and the etiology remains unknown. Treatment modalities for AF typically include rate control medications, antiarrhythmics and radio frequency ablation (RFA), each of which is accompanied by its own risk of complications. We report a case of symptomatic AF that was refractory to multiple antiarrhythmics and an RFA procedure which resolved with prednisone. In this case, AF was associated with cardiac sarcoidosis, a disorder that is thought to be due to granulomatous involvement of the myocardium and increased systemic inflammation.

  20. Hippocampal activation of microglia may underlie the shared neurobiology of comorbid posttraumatic stress disorder and chronic pain

    PubMed Central

    Sun, Rao; Zhang, Zuoxia; Lei, Yishan; Liu, Yue; Lu, Cui’e; Rong, Hui; Sun, Yu’e; Zhang, Wei; Gu, Xiaoping

    2016-01-01

    The high comorbidity rates of posttraumatic stress disorder and chronic pain have been widely reported, but the underlying mechanisms remain unclear. Emerging evidence suggested that an excess of inflammatory immune activities in the hippocampus involved in the progression of both posttraumatic stress disorder and chronic pain. Considering that microglia are substrates underlying the initiation and propagation of the neuroimmune response, we hypothesized that stress-induced activation of hippocampal microglia may contribute to the pathogenesis of posttraumatic stress disorder-pain comorbidity. We showed that rats exposed to single prolonged stress, an established posttraumatic stress disorder model, exhibited persistent mechanical allodynia and anxiety-like behavior, which were accompanied by increased activation of microglia and secretion of pro-inflammatory cytokines in the hippocampus. Correlation analyses showed that hippocampal activation of microglia was significantly correlated with mechanical allodynia and anxiety-like behavior. Our data also showed that both intraperitoneal and intra-hippocampal injection of minocycline suppressed single prolonged stress-induced microglia activation and inflammatory cytokines accumulation in the hippocampus, and attenuated both single prolonged stress-induced mechanical allodynia and anxiety-like behavior. Taken together, the present study suggests that stress-induced microglia activation in the hippocampus may serve as a critical mechanistic link in the comorbid relationship between posttraumatic stress disorder and chronic pain. The novel concept introduces the possibility of cotreating chronic pain and posttraumatic stress disorder. PMID:27852966

  1. A Novel Cardioprotective Agent in Cardiac Transplantation: Metformin Activation of AMP-Activated Protein Kinase Decreases Acute Ischemia-Reperfusion Injury and Chronic Rejection

    PubMed Central

    Chin, Jocelyn T.; Troke, Joshua J.; Kimura, Naoyuki; Itoh, Satoshi; Wang, Xi; Palmer, Owen P.; Robbins, Robert C.; Fischbein, Michael P.

    2011-01-01

    The main cause of mortality after the first year from cardiac transplantation is cardiac allograft vasculopathy (CAV), which leads to chronic rejection of the heart. To improve long-term outcomes in cardiac transplantation, treatments to prevent or diminish CAV are actively being researched. Ischemia-reperfusion (I-R) injury has been shown to be the strongest alloantigen-independent factor in the development of CAV. Here, we investigate the use of metformin in murine cardiac transplantation models as a novel cardioprotective agent to limit acute I-R injury and subsequent chronic rejection. We show that metformin treatment activates AMP-activated kinase (AMPK) in vitro and in vivo. In the acute transplantation model, metformin activation of AMPK resulted in significantly decreased apoptosis in cardiac allografts on postoperative day (POD) 1 and 8. In the chronic transplantation model, metformin pretreatment of allografts led to significantly improved graft function and significantly decreased CAV, as measured on POD 52. Taken together, our results in the acute and chronic rejection studies suggest a potential cardioprotective mechanism for metformin; we demonstrate a correlation between metformin-induced decrease in acute I-R injury and metformin-related decrease in chronic rejection. Thus, one of the ways by which metformin and AMPK activation may protect the transplanted heart from chronic rejection is by decreasing initial I-R injury inherent in donor organ preservation and implantation. Our findings suggest novel therapeutic strategies for minimizing chronic cardiac rejection via the use of metformin- and AMPK-mediated pathways to suppress acute I-R injury. PMID:22180679

  2. A novel cardioprotective agent in cardiac transplantation: metformin activation of AMP-activated protein kinase decreases acute ischemia-reperfusion injury and chronic rejection.

    PubMed

    Chin, Jocelyn T; Troke, Joshua J; Kimura, Naoyuki; Itoh, Satoshi; Wang, Xi; Palmer, Owen P; Robbins, Robert C; Fischbein, Michael P

    2011-12-01

    The main cause of mortality after the first year from cardiac transplantation is cardiac allograft vasculopathy (CAV), which leads to chronic rejection of the heart. To improve long-term outcomes in cardiac transplantation, treatments to prevent or diminish CAV are actively being researched. Ischemia-reperfusion (I-R) injury has been shown to be the strongest alloantigen-independent factor in the development of CAV. Here, we investigate the use of metformin in murine cardiac transplantation models as a novel cardioprotective agent to limit acute I-R injury and subsequent chronic rejection. We show that metformin treatment activates AMP-activated kinase (AMPK) in vitro and in vivo. In the acute transplantation model, metformin activation of AMPK resulted in significantly decreased apoptosis in cardiac allografts on postoperative day (POD) 1 and 8. In the chronic transplantation model, metformin pretreatment of allografts led to significantly improved graft function and significantly decreased CAV, as measured on POD 52. Taken together, our results in the acute and chronic rejection studies suggest a potential cardioprotective mechanism for metformin; we demonstrate a correlation between metformin-induced decrease in acute I-R injury and metformin-related decrease in chronic rejection. Thus, one of the ways by which metformin and AMPK activation may protect the transplanted heart from chronic rejection is by decreasing initial I-R injury inherent in donor organ preservation and implantation. Our findings suggest novel therapeutic strategies for minimizing chronic cardiac rejection via the use of metformin- and AMPK-mediated pathways to suppress acute I-R injury.

  3. PP2A-activating drugs selectively eradicate TKI-resistant chronic myeloid leukemic stem cells

    PubMed Central

    Neviani, Paolo; Harb, Jason G.; Oaks, Joshua J.; Santhanam, Ramasamy; Walker, Christopher J.; Ellis, Justin J.; Ferenchak, Gregory; Dorrance, Adrienne M.; Paisie, Carolyn A.; Eiring, Anna M.; Ma, Yihui; Mao, Hsiaoyin C.; Zhang, Bin; Wunderlich, Mark; May, Philippa C.; Sun, Chaode; Saddoughi, Sahar A.; Bielawski, Jacek; Blum, William; Klisovic, Rebecca B.; Solt, Janelle A.; Byrd, John C.; Volinia, Stefano; Cortes, Jorge; Huettner, Claudia S.; Koschmieder, Steffen; Holyoake, Tessa L.; Devine, Steven; Caligiuri, Michael A.; Croce, Carlo M.; Garzon, Ramiro; Ogretmen, Besim; Arlinghaus, Ralph B.; Chen, Ching-Shih; Bittman, Robert; Hokland, Peter; Roy, Denis-Claude; Milojkovic, Dragana; Apperley, Jane; Goldman, John M.; Reid, Alistair; Mulloy, James C.; Bhatia, Ravi; Marcucci, Guido; Perrotti, Danilo

    2013-01-01

    The success of tyrosine kinase inhibitors (TKIs) in treating chronic myeloid leukemia (CML) depends on the requirement for BCR-ABL1 kinase activity in CML progenitors. However, CML quiescent HSCs are TKI resistant and represent a BCR-ABL1 kinase–independent disease reservoir. Here we have shown that persistence of leukemic HSCs in BM requires inhibition of the tumor suppressor protein phosphatase 2A (PP2A) and expression — but not activity — of the BCR-ABL1 oncogene. Examination of HSCs from CML patients and healthy individuals revealed that PP2A activity was suppressed in CML compared with normal HSCs. TKI-resistant CML quiescent HSCs showed increased levels of BCR-ABL1, but very low kinase activity. BCR-ABL1 expression, but not kinase function, was required for recruitment of JAK2, activation of a JAK2/β-catenin survival/self-renewal pathway, and inhibition of PP2A. PP2A-activating drugs (PADs) markedly reduced survival and self-renewal of CML quiescent HSCs, but not normal quiescent HSCs, through BCR-ABL1 kinase–independent and PP2A-mediated inhibition of JAK2 and β-catenin. This led to suppression of human leukemic, but not normal, HSC/progenitor survival in BM xenografts and interference with long-term maintenance of BCR-ABL1–positive HSCs in serial transplantation assays. Targeting the JAK2/PP2A/β-catenin network in quiescent HSCs with PADs (e.g., FTY720) has the potential to treat TKI-refractory CML and relieve lifelong patient dependence on TKIs. PMID:23999433

  4. Activated Allogeneic NK Cells Preferentially Kill Poor Prognosis B-Cell Chronic Lymphocytic Leukemia Cells.

    PubMed

    Sánchez-Martínez, Diego; Lanuza, Pilar M; Gómez, Natalia; Muntasell, Aura; Cisneros, Elisa; Moraru, Manuela; Azaceta, Gemma; Anel, Alberto; Martínez-Lostao, Luis; Villalba, Martin; Palomera, Luis; Vilches, Carlos; García Marco, José A; Pardo, Julián

    2016-01-01

    Mutational status of TP53 together with expression of wild-type (wt) IGHV represents the most widely accepted biomarkers, establishing a very poor prognosis in B-cell chronic lymphocytic leukemia (B-CLL) patients. Adoptive cell therapy using allogeneic HLA-mismatched Natural killer (NK) cells has emerged as an effective and safe alternative in the treatment of acute myeloid and lymphoid leukemias that do not respond to traditional therapies. We have described that allogeneic activated NK cells eliminate hematological cancer cell lines with multidrug resistance acquired by mutations in the apoptotic machinery. This effect depends on the activation protocol, being B-lymphoblastoid cell lines (LCLs) the most effective stimulus to activate NK cells. Here, we have further analyzed the molecular determinants involved in allogeneic NK cell recognition and elimination of B-CLL cells, including the expression of ligands of the main NK cell-activating receptors (NKG2D and NCRs) and HLA mismatch. We present preliminary data suggesting that B-CLL susceptibility significantly correlates with HLA mismatch between NK cell donor and B-CLL patient. Moreover, we show that the sensitivity of B-CLL cells to NK cells depends on the prognosis based on TP53 and IGHV mutational status. Cells from patients with worse prognosis (mutated TP53 and wt IGHV) are the most susceptible to activated NK cells. Hence, B-CLL prognosis may predict the efficacy of allogenic activated NK cells, and, thus, NK cell transfer represents a good alternative to treat poor prognosis B-CLL patients who present a very short life expectancy due to lack of effective treatments.

  5. Activated Allogeneic NK Cells Preferentially Kill Poor Prognosis B-Cell Chronic Lymphocytic Leukemia Cells

    PubMed Central

    Sánchez-Martínez, Diego; Lanuza, Pilar M.; Gómez, Natalia; Muntasell, Aura; Cisneros, Elisa; Moraru, Manuela; Azaceta, Gemma; Anel, Alberto; Martínez-Lostao, Luis; Villalba, Martin; Palomera, Luis; Vilches, Carlos; García Marco, José A.; Pardo, Julián

    2016-01-01

    Mutational status of TP53 together with expression of wild-type (wt) IGHV represents the most widely accepted biomarkers, establishing a very poor prognosis in B-cell chronic lymphocytic leukemia (B-CLL) patients. Adoptive cell therapy using allogeneic HLA-mismatched Natural killer (NK) cells has emerged as an effective and safe alternative in the treatment of acute myeloid and lymphoid leukemias that do not respond to traditional therapies. We have described that allogeneic activated NK cells eliminate hematological cancer cell lines with multidrug resistance acquired by mutations in the apoptotic machinery. This effect depends on the activation protocol, being B-lymphoblastoid cell lines (LCLs) the most effective stimulus to activate NK cells. Here, we have further analyzed the molecular determinants involved in allogeneic NK cell recognition and elimination of B-CLL cells, including the expression of ligands of the main NK cell-activating receptors (NKG2D and NCRs) and HLA mismatch. We present preliminary data suggesting that B-CLL susceptibility significantly correlates with HLA mismatch between NK cell donor and B-CLL patient. Moreover, we show that the sensitivity of B-CLL cells to NK cells depends on the prognosis based on TP53 and IGHV mutational status. Cells from patients with worse prognosis (mutated TP53 and wt IGHV) are the most susceptible to activated NK cells. Hence, B-CLL prognosis may predict the efficacy of allogenic activated NK cells, and, thus, NK cell transfer represents a good alternative to treat poor prognosis B-CLL patients who present a very short life expectancy due to lack of effective treatments. PMID:27833611

  6. Unconventional Role of Caspase-6 in Spinal Microglia Activation and Chronic Pain

    PubMed Central

    Lee, Jee Eun

    2017-01-01

    Chronic pain affects ~20% of the worldwide population. The clinical management of chronic pain is mostly palliative and results in limited success. Current treatments mostly target the symptoms or neuronal signaling of chronic pain. It has been increasingly recognized that glial cells, such as microglia, and inflammatory signaling play a major role in the pathogenesis of chronic pain. Caspases (CASPs) are a family of protease enzymes involved in apoptosis and inflammation. They are pivotal components in a variety of neurological diseases. However, little is known about the role of CASPs in microglial modulation as to chronic pain. In particular, our recent studies have shown that CASP6 regulates chronic pain via microglial inflammatory signaling. Inhibition of microglia and CASP signaling might provide a new strategy for the prevention and treatment of chronic pain. PMID:28270702

  7. Unconventional Role of Caspase-6 in Spinal Microglia Activation and Chronic Pain.

    PubMed

    Berta, Temugin; Lee, Jee Eun; Park, Chul-Kyu

    2017-01-01

    Chronic pain affects ~20% of the worldwide population. The clinical management of chronic pain is mostly palliative and results in limited success. Current treatments mostly target the symptoms or neuronal signaling of chronic pain. It has been increasingly recognized that glial cells, such as microglia, and inflammatory signaling play a major role in the pathogenesis of chronic pain. Caspases (CASPs) are a family of protease enzymes involved in apoptosis and inflammation. They are pivotal components in a variety of neurological diseases. However, little is known about the role of CASPs in microglial modulation as to chronic pain. In particular, our recent studies have shown that CASP6 regulates chronic pain via microglial inflammatory signaling. Inhibition of microglia and CASP signaling might provide a new strategy for the prevention and treatment of chronic pain.

  8. Eosinophil activation of fibroblasts from chronic allergen-induced disease utilizes stem cell factor for phenotypic changes.

    PubMed

    Dolgachev, Vladislav; Berlin, Aaron A; Lukacs, Nicholas W

    2008-01-01

    In the present studies the role of stem cell factor (SCF) in mediating eosinophil and fibroblast activation during their interaction was investigated. SCF was significantly higher in fibroblasts grown from lungs of chronic allergen-challenged mice compared to fibroblasts grown from normal mice. When eosinophils were layered onto fibroblasts from allergic mice, a significant increase in SCF was detected compared to fibroblasts from nonallergic mice. The interaction of fibroblasts with eosinophils also increased the production of asthma-associated chemokines, CCL5 and CCL6, was dependent on cell-to-cell interaction, and was observed only with fibroblasts derived from lungs of chronic allergen-challenged mice and not from those derived from unchallenged normal mice. Chemokine production was significantly decreased when anti-SCF antibodies were added during eosinophil-fibroblast interaction. The interaction of fibroblasts from chronic allergen-challenged mice with eosinophils also increased alpha-smooth muscle cell actin and procollagen I expression as well as induced transforming growth factor-beta. The changes in myofibroblast activation were dependent on SCF-mediated pathways because anti-SCF antibody treatment reduced the expression of all three of these latter fibrosis-associated markers. Thus, our data suggest that SCF mediates an important activation pathway for fibroblasts during chronic allergic responses on interaction with recruited eosinophils and suggest a potential mechanism of airway remodeling during chronic disease.

  9. Opioid-induced mitogen-activated protein kinase signaling in rat enteric neurons following chronic morphine treatment.

    PubMed

    Duraffourd, Celine; Kumala, Erica; Anselmi, Laura; Brecha, Nicholas C; Sternini, Catia

    2014-01-01

    Opioids, acting at μ opioid receptors, are commonly used for pain management. Chronic opioid treatment induces cellular adaptations, which trigger long-term side effects, including constipation mediated by enteric neurons. We tested the hypothesis that chronic opioid treatment induces alterations of μ opioid receptor signaling in enteric neurons, which are likely to serve as mechanisms underlying opioid-induced constipation. In cultured rat enteric neurons, either untreated (naïve) or exposed to morphine for 4 days (chronic), we compared the effect of morphine and DAMGO (D-Ala2,MePhe4,Gly-ol5 enkephalin) on μ opioid receptor internalization and downstream signaling by examining the activation of the mitogen-activated protein kinase/extracellular signal-regulated kinases 1 and 2 (MAPK/ERK) pathway, cAMP accumulation and transcription factor cAMP Response Element-Binding protein (CREB) expression. μ opioid receptor internalization and MAPK/ERK phosphorylation were induced by DAMGO, but not morphine in naïve neurons, and by both opioids in chronic neurons. MAPK/ERK activation was prevented by the receptor antagonist naloxone, by blocking receptor trafficking with hypertonic sucrose, dynamin inhibitor, or neuronal transfection with mutated dynamin, and by MAPK inhibitor. Morphine and DAMGO inhibited cAMP in naïve and chronic enteric neurons, and induced desensitization of cAMP signaling. Chronic morphine treatment suppressed desensitization of cAMP and MAPK signaling, increased CREB phosphorylation through a MAPK/ERK pathway and induced delays of gastrointestinal transit, which was prevented by MAPK/ERK blockade. This study showed that opioids induce endocytosis- and dynamin-dependent MAPK/ERK activation in enteric neurons and that chronic morphine treatment triggers changes at the receptor level and downstream signaling resulting in MAPK/ERK-dependent CREB activation. Blockade of this signaling pathway prevents the development of gastrointestinal motility

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

    PubMed Central

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

    2014-01-01

    Herein, we investigated the effects of a ballet class on the kinetic profiles of creatine kinase (CK) and lactate dehydrogenase (LDH) activities, cytokines, complement component 3 (C3), and the concentrations of immunoglobulin (Ig), IgA and IgM, in ballerinas. We also verified neutrophil death and ROS release. Blood samples were taken from 13 dancers before, immediately after, and 18 hours after a ballet class. The ballet class increased the plasma activities of CK-total (2.0-fold) immediately after class, while the activities of CK-cardiac muscle (1.0-fold) and LDH (3.0-fold) were observed to increase 18 hours after the class. Levels of the TNF-α, IL-1β, IgG, and IgA were not affected under the study conditions. The exercise was found to induce neutrophil apoptosis (6.0-fold) 18 hours after the ballet class. Additionally, immediately after the ballet class, the neutrophils from the ballerinas were found to be less responsive to PMA stimulus. Conclusion. Ballet class was found to result in inflammation in dancers. The inflammation caused by the ballet class remained for 18 hours after the exercise. These findings are important in preventing the development of chronic lesions that are commonly observed in dancers, such as those with arthritis and synovitis. PMID:24701035

  11. Study of Repetitive Movements Induced Oscillatory Activities in Healthy Subjects and Chronic Stroke Patients

    PubMed Central

    Hsu, Chuan-Chih; Lee, Wai-Keung; Shyu, Kuo-Kai; Chang, Hsiao-Huang; Yeh, Ting-Kuang; Hsu, Hao-Teng; Chang, Chun-Yen; Lan, Gong-Yau; Lee, Po-Lei

    2016-01-01

    Repetitive movements at a constant rate require the integration of internal time counting and motor neural networks. Previous studies have proved that humans can follow short durations automatically (automatic timing) but require more cognitive efforts to track or estimate long durations. In this study, we studied sensorimotor oscillatory activities in healthy subjects and chronic stroke patients when subjects were performing repetitive finger movements. We found the movement-modulated changes in alpha and beta oscillatory activities were decreased with the increase of movement rates in finger lifting of healthy subjects and the non-paretic hands in stroke patients, whereas no difference was found in the paretic-hand movements at different movement rates in stroke patients. The significant difference in oscillatory activities between movements of non-paretic hands and paretic hands could imply the requirement of higher cognitive efforts to perform fast repetitive movements in paretic hands. The sensorimotor oscillatory response in fast repetitive movements could be a possible indicator to probe the recovery of motor function in stroke patients. PMID:27976723

  12. A Carboxyl Ester Lipase (CEL) Mutant Causes Chronic Pancreatitis by Forming Intracellular Aggregates That Activate Apoptosis.

    PubMed

    Xiao, Xunjun; Jones, Gabrielle; Sevilla, Wednesday A; Stolz, Donna B; Magee, Kelsey E; Haughney, Margaret; Mukherjee, Amitava; Wang, Yan; Lowe, Mark E

    2016-10-28

    Patients with chronic pancreatitis (CP) frequently have genetic risk factors for disease. Many of the identified genes have been connected to trypsinogen activation or trypsin inactivation. The description of CP in patients with mutations in the variable number of tandem repeat (VNTR) domain of carboxyl ester lipase (CEL) presents an opportunity to study the pathogenesis of CP independently of trypsin pathways. We tested the hypothesis that a deletion and frameshift mutation (C563fsX673) in the CEL VNTR causes CP through proteotoxic gain-of-function activation of maladaptive cell signaling pathways including cell death pathways. HEK293 or AR42J cells were transfected with constructs expressing CEL with 14 repeats in the VNTR (CEL14R) or C563fsX673 CEL (CEL maturity onset diabetes of youth with a deletion mutation in the VNTR (MODY)). In both cell types, CEL MODY formed intracellular aggregates. Secretion of CEL MODY was decreased compared with that of CEL14R. Expression of CEL MODY increased endoplasmic reticulum stress, activated the unfolded protein response, and caused cell death by apoptosis. Our results demonstrate that disorders of protein homeostasis can lead to CP and suggest that novel therapies to decrease the intracellular accumulation of misfolded protein may be successful in some patients with CP.

  13. Connective tissue growth factor production by activated pancreatic stellate cells in mouse alcoholic chronic pancreatitis

    PubMed Central

    Charrier, Alyssa; Brigstock, David R.

    2010-01-01

    Alcoholic chronic pancreatitis (ACP) is characterized by pancreatic necrosis, inflammation, and scarring, the latter of which is due to excessive collagen deposition by activated pancreatic stellate cells (PSC). The aim of this study was to establish a model of ACP in mice, a species that is usually resistant to the toxic effects of alcohol, and to identify the cell type(s) responsible for production of connective tissue growth factor (CTGF), a pro-fibrotic molecule. C57Bl/6 male mice received intraperitoneal ethanol injections for three weeks against a background of cerulein-induced acute pancreatitis. Peak blood alcohol levels remained consistently high in ethanol-treated mice as compared to control mice. In mice receiving ethanol plus cerulein, there was increased collagen deposition as compared to other treatment groups as well as increased frequency of α-smooth muscle actin and desmin-positive PSC which also demonstrated significantly enhanced CTGF protein production. Expression of mRNA for collagen α1(I), α-smooth muscle actin or CTGF were all increased and co-localized exclusively to activated PSC in ACP. Pancreatic expression of mRNA for key profibrotic markers were all increased in ACP. In conclusion, a mouse model of ACP has been developed that mimics key pathophysiological features of the disease in humans and which shows that activated PSC are the principal producers of collagen and CTGF. PSC-derived CTGF is thus a candidate therapeutic target in anti-fibrotic strategies for ACP. PMID:20368699

  14. Chronic activation of CB2 cannabinoid receptors in the hippocampus increases excitatory synaptic transmission

    PubMed Central

    Kim, Jimok; Li, Yong

    2015-01-01

    The roles of CB1 cannabinoid receptors in regulating neuronal activity have been extensively characterized. Although early studies show that CB1 receptors are present in the nervous system and CB2 cannabinoid receptors are in the immune system, recent evidence indicates that CB2 receptors are also expressed in the brain. Activation or blockade of CB2 receptors in vivo induces neuropsychiatric effects, but the cellular mechanisms of CB2 receptor function are unclear. The aim of this study is to determine how activation of CB2 receptors present in the hippocampus regulates synaptic function. Here, we show that when organotypic cultures of rodent hippocampal slices were treated with a CB2 receptor agonist (JWH133 or GP1a) for 7–10 days, quantal glutamate release became more frequent and spine density was increased via extracellular signal-regulated kinases. Chronic intraperitoneal injection of JWH133 into mice also increased excitatory synaptic transmission. These effects were blocked by a CB2 receptor antagonist (SR144528) or absent from hippocampal slices of CB2 receptor knock-out mice. This study reveals a novel cellular function of CB2 cannabinoid receptors in the hippocampus and provides insights into how cannabinoid receptor subtypes diversify the roles of cannabinoids in the brain. PMID:25504573

  15. Effects of women's stress-elicited physiological activity and chronic anxiety on fetal heart rate.

    PubMed

    Monk, Catherine; Myers, Michael M; Sloan, Richard P; Ellman, Lauren M; Fifer, William P

    2003-02-01

    This study examined the effects of pregnant women's acute stress reactivity and chronic anxiety on fetal heart rate (HR). Thirty-two healthy third trimester pregnant women were instrumented to monitor continuous electrocardiography, blood pressure, respiration, and fetal HR. Subjects completed the trait anxiety subscale of the State Trait Anxiety Index, then rested quietly for a 5-minute baseline period, followed by a 5-minute Stroop color-word matching task and a 5-minute recovery period. Fetal HR changes during women's recovery from a stressful task were associated with the women's concurrently collected HR and blood pressure changes (r =.63, p <.05). Fetal HR changes during recovery, as well as during women's exposure to the Stroop task, were correlated with their mothers' trait anxiety scores (r =.39, p <.05 and r = -.52, p <.01, respectively). Finally, a combination of measures of women's cardiovascular activity during recovery and trait anxiety scores accounted for two thirds of the variance in fetal HR changes during the same recovery period (r =.69, p <.001). The results from this study link changes in fetal behavior with acute changes in women's cardiovascular activity after psychological stress and women's anxiety status. This indicates that variations in women's emotion-based physiological activity can affect the fetus and may be centrally important to fetal development.

  16. Paraproteins with antibody activity in acute viral hepatitis and chronic autoimmune liver diseases

    PubMed Central

    Roux, Maria E. B.; Florin-Christensen, A.; Arana, R. M.; Doniach, Deborah

    1974-01-01

    Of 27 patients with liver disease and cryoglobulinaemia 18 proved to have paraproteins. Six of these monoclonal immunoglobulins were shown to have antibody activity, directed to human gamma globulin, alpha1-fetoprotein, smooth muscle, and mitochondria. Eight of the patients suffered from acute viral hepatitis, five of whom were HB Ag positive; in all these cases the monoclonal spikes were transient and their antibody activities were directed against IgG in two cases and alpha1-fetoprotein in one. Seven of the patients had active chronic hepatitis and in these the paraproteinaemia persisted, though remaining quantitatively unchanged over several years. One of them had a cryoprecipitable monoclonal smooth muscle antibody. Three patients had primary biliary cirrhosis and in two of them monoclonal IgM mitochondrial antibodies were demonstrated. In three out of the 18 cases there was a double M-component. Since these monoclonal antibodies are directed to autoantigens not unlike the polyclonal ones usually seen in autoimmune hepatic diseases, it is suggested that the factor which triggers the uncontrolled plasma cell proliferation to produce paraproteins must meet cells from an already expanding clone. PMID:18668850

  17. [Chronic diseases of the ankle joint].

    PubMed

    Rand, T; Trattnig, S; Breitenseher, M; Kreuzer, S; Wagesreither, S; Imhof, H

    1999-01-01

    The etiology of chronic diseases of the ankle joint comprises a wide spectrum including chronic inflammatory processes and chronic degenerative, tumorous and neuropathic processes, as well as some specific syndromes based on chronic changes of the ankle joint. Of the inflammatory processes, chronic juvenile arthritis (JVC) is the most common disease. However, also Reiter disease, psoriasis or chronic monoarthritid diseases such as gout, as well as granulomatous diseases (tuberculosis, sarcoidosis) and fungal infections, may affect the ankle joint in a chronic course. Chronic degenerative changes are usually secondary due to abnormal positioning of the joint constituents or repetitive trauma. Neuropathic changes, as frequently seen in the course of diabetes, present with massive osseous destruction and malposition of the articular constituents. Chronic osseous as well as cartilaginous and synovial changes are seen in hemophilic patients. Chronic traumatic changes are represented by pigmented villonodular synovitis (PVNS), and chondromatosis, both with a predilection for the ankle joint. Due to the possibilities of magnetic resonance imaging (MRI), diagnosis of chronic ankle changes includes chronic ligamentous, tendinous and soft tissue changes. With the use of MRI, specific syndromes can be defined which particularly affect the ankle joint in a chronic way, such as the os trigonum syndrome, the anterolateral impingement syndrome and the sinus tarsi syndrome. Nevertheless, plain film radiographs are still the basic element of any investigation. MRI, however, can be potentially used as a second investigation, saving an unnecessary cascade of investigations with ultrasound and CT. The latter investigations are used only with very specific indications, for instance CT for subtle bone structures and sonography for a limited investigation of tendons or evaluation of fluid. Particularly due to the possibilities of MRI and the development of special gradient-echo imaging

  18. Physical Activity, Health Status and Risk of Hospitalization in Patients with Severe Chronic Obstructive Pulmonary Disease

    PubMed Central

    Benzo, Roberto P.; Chang, Chung-Chou H.; Farrell, Max H.; Kaplan, Robert; Ries, Andrew; Martinez, Fernando J.; Wise, Robert; Make, Barry; Sciurba, Frank

    2010-01-01

    Background Chronic obstructive pulmonary disease (COPD) is a leading cause of death and 70% of the cost of COPD is due to hospitalizations. Self-reported daily physical activity and health status have been reported as predictors of a hospitalization in COPD but are not routinely assessed. Objectives We tested the hypothesis that self-reported daily physical activity and health status assessed by a simple question were predictors of a hospitalization in a well-characterized cohort of patients with severe emphysema. Methods Investigators gathered daily physical activity and health status data assessed by a simple question in 597 patients with severe emphysema and tested the association of those patient-reported outcomes to the occurrence of a hospitalization in the following year. Multiple logistic regression analyses were used to determine predictors of hospitalization during the first 12 months after randomization. Results The two variables tested in the hypothesis were significant predictors of a hospitalization after adjusting for all univariable significant predictors: >2 h of physical activity per week had a protective effect [odds ratio (OR) 0.60; 95% confidence interval (95% CI) 0.41–0.88] and self-reported health status as fair or poor had a deleterious effect (OR 1.57; 95% CI 1.10–2.23). In addition, two other variables became significant in the multivariate model: total lung capacity (every 10% increase) had a protective effect (OR 0.88; 95% CI 0.78–0.99) and self-reported anxiety had a deleterious effect (OR 1.75; 95% CI 1.13–2.70). Conclusion Self-reported daily physical activity and health status are independently associated with COPD hospitalizations. Our findings, assessed by simple questions, suggest the value of patient-reported outcomes in developing risk assessment tools that are easy to use. PMID:20234126

  19. Conditioned place preference and spontaneous dorsal horn neuron activity in chronic constriction injury model in rats

    PubMed Central

    Dalm, Brian D.; Reddy, Chandan G.; Howard, Matthew A.; Kang, Sinyoung; Brennan, Timothy J.

    2016-01-01

    Patients with neuropathic pain commonly present with spontaneous pain, in addition to allodynia and hyperalgesia. While evoked responses in neuropathic pain models are well characterized, determining the presence of spontaneous pain is more challenging. We determined if the chronic constriction injury (CCI) model could be used to measure effects of treatment of spontaneous pain, by evaluating dorsal horn neuron (DHN) spontaneous activity and spontaneous pain-related behaviors. We measured conditioned place preference (CPP) to analgesia produced by sciatic nerve block with bupivacaine in rats with established CCI. We undertook another CPP experiment using hindpaw incision. We also examined DHN spontaneous activity in CCI rats. While CCI produced nocifensive responses to mechanical stimuli, CPP to analgesic nerve block was not evident 14 days following injury: Compared to baseline (314 ± 65 sec), CCI rats did not show a preference for the bupivacaine-paired chamber following conditioning (330 ± 102 sec). On the other hand, sciatic nerve block after hindpaw incision produced CPP on postoperative day 1, serving as a positive control. The proportion of spontaneously active DHNs (33%) was not significantly increased in CCI rats compared to the sham (21%). The median rate of spontaneous activity in the CCI group (12.6 imp/s) was not different from the sham group (9.2 imp/s). Also, there was no change in DHN spontaneous activity following sciatic nerve block with bupivacaine. Our findings suggest that CCI as a neuropathic pain model should not be used to measure effects of treatment of spontaneous pain driven by the peripheral input. PMID:26584420

  20. Acetylcholinesterase activity in the pons and medulla oblongata of rats after chronic electroconvulsive shock.

    PubMed

    Camarini, R; Benedito, M A

    1997-10-01

    An imbalance between cholinergic and noradrenergic neurotransmission has been proposed for the etiology of affective disorders. According to this hypothesis, depression would be the result of enhanced cholinergic and reduced noradrenergic neurotransmission. Repeated electroconvulsive shock (ECS) is an effective treatment for depression; moreover, in laboratory animals it induces changes in brain noradrenergic neurotransmission similar to those obtained by chronic treatment with antidepressant drugs (down-regulation of beta-adrenergic receptors). The aim of the present study was to determine whether repeated ECS in rats changes acetylcholinesterase (Achase) activity. Achase controls the level of acetylcholine (Ach) in the synaptic cleft and its levels seem to be regulated by the interaction between Ach and its receptor. Thus, a decrease in Achase activity would suggest decreased cholinergic activity. Adult male Wistar rats received one ECS (80 mA, 0.2 s, 60 Hz) daily for 7 days. Control rats were handled in the same way without receiving the shock. Rats were sacrificed 24 h after the last ECS and membrane-bound and soluble Achase activity was assayed in homogenates obtained from the pons and medulla oblongata. A statistically significant decrease in membrane-bound Achase activity (nmol thiocholine formed min-1 mg protein-1) (control 182.6 +/- 14.8, ECS 162.2 +/- 14.2, P < 0.05) and an increase in soluble Achase activity in the medulla oblongata (control 133.6 +/- 4.2, ECS 145.8 +/- 12.3, P < 0.05) were observed. No statistical differences were observed in Achase activity in the pons. Although repeated ECS induced a decrease in membrane-bound Achase activity, the lack of changes in the pons (control Achase activity: total 231.0 +/- 34.5, membrane-bound 298.9 +/- 18.5, soluble 203.9 +/- 30.9), the region where the locus coeruleus, the main noradrenergic nucleus, is located, does not seem to favor the existence of an interaction between cholinergic and noradrenergic

  1. [Impact of physical activity on metabolic control and the development of chronic complications in patients with type 1 diabetes mellitus].

    PubMed

    Carral San Laureano, Florentino; Gutiérrez Manzanedo, José Vicente; Ayala Ortega, Carmen; García Calzado, Concepción; Silva Rodríguez, Juan José; Aguilar Diosdado, Manuel

    2010-01-01

    Together with a balanced diet, regular physical activity is one of the pillars of diabetes mellitus (DM) management. Physical activity theoretically provides the same advantages in people with DM as in the general population and also has some beneficial effects in controlling metabolic factors, such as improving blood glucose levels and insulin sensitivity. In this article, we analyze the main clinical studies published to date that evaluate the impact of physical activity on metabolic control or the development of chronic complications in patients with type 1 diabetes mellitus. In conclusion, most of the evaluated studies show that regular physical activity favorably affects metabolic control in DM (or at least does not have adverse effects). However, there is insufficient information about the impact of physical activity on the development and progression of chronic complications.

  2. A systematic review of interventions aimed at increasing physical activity in adults with chronic musculoskeletal pain—protocol

    PubMed Central

    2014-01-01

    Background Chronic musculoskeletal pain is highly prevalent, affecting around one in five people across Europe. Osteoarthritis, low back pain, neck pain and other musculoskeletal disorders are leading causes of disability worldwide and the most common source of chronic pain. Exercise and/or physical activity interventions have the potential to address not only th