Science.gov

Sample records for activity disease activity

  1. Being active when you have heart disease

    MedlinePlus

    Heart disease - activity; CAD - activity; Coronary artery disease - activity; Angina - activity ... Getting regular exercise when you have heart disease is important. Exercise can make your heart muscle stronger. It may also help you be more active without chest pain or ...

  2. Cardiovascular Disease and Cancer: Student Awareness Activities.

    ERIC Educational Resources Information Center

    Meyer, James H., Comp.

    Awareness activities pertaining to cancer and cardiovascular disease are presented as a supplement for high school science classes. The exercises can be used to enrich units of study dealing with the circulatory system, the cell, or human diseases. Eight activities deal with the following topics: (1) cardiovascular disease risk factors; (2)…

  3. Activity.

    ERIC Educational Resources Information Center

    Clearing: Nature and Learning in the Pacific Northwest, 1984

    1984-01-01

    Presents three activities: (1) investigating succession in a schoolground; (2) investigating oak galls; and (3) making sun prints (photographs made without camera or darkroom). Each activity includes a list of materials needed and procedures used. (JN)

  4. Physical Activity Fundamental to Preventing Disease.

    ERIC Educational Resources Information Center

    Office of the Assistant Secretary for Planning and Evaluation (DHHS), Washington, DC.

    Regular physical activity, fitness, and exercise are critically important for all people's health and wellbeing. It can reduce morbidity and mortality from many chronic diseases. Despite its well-known benefits, most U.S. adults, and many children, are not active enough to achieve these health benefits. Physical inactivity and related health…

  5. 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

  6. Activities.

    ERIC Educational Resources Information Center

    Bippert, Judy

    1993-01-01

    Presents activities designed to give students an opportunity to solve concrete problems involving spatial relationships and logical thinking utilizing hands-on manipulatives. Provides teacher instructions and four reproducible worksheets. (MDH)

  7. Glia, sympathetic activity and cardiovascular disease

    PubMed Central

    Teschemacher, Anja G.; Kasparov, Sergey; Gourine, Alexander V.

    2016-01-01

    New Findings What is the topic of this review? In this review, we discuss recent findings that provide a novel insight into the mechanisms that link glial cell function with the pathogenesis of cardiovascular disease, including systemic arterial hypertension and chronic heart failure. What advances does it highlight? We discuss how glial cells may influence central presympathetic circuits, leading to maladaptive and detrimental increases in sympathetic activity and contributing to the development and progression of cardiovascular disease. Increased activity of the sympathetic nervous system is associated with the development of cardiovascular disease and may contribute to its progression. Vasomotor and cardiac sympathetic activities are generated by the neuronal circuits located in the hypothalamus and the brainstem. These neuronal networks receive multiple inputs from the periphery and other parts of the CNS and, at a local level, may be influenced by their non‐neuronal neighbours, in particular glial cells. In this review, we discuss recent experimental evidence suggesting that astrocytes and microglial cells are able to modulate the activity of sympathoexcitatory neural networks in disparate physiological and pathophysiological conditions. We focus on the chemosensory properties of astrocytes residing in the rostral ventrolateral medulla oblongata and discuss signalling mechanisms leading to glial activation during brain hypoxia and inflammation. Alterations in these mechanisms may lead to heightened activity of sympathoexcitatory CNS circuits and contribute to maladaptive and detrimental increases in sympathetic tone associated with systemic arterial hypertension and chronic heart failure. PMID:26988631

  8. Activities.

    ERIC Educational Resources Information Center

    Kincaid, Charlene; And Others

    1993-01-01

    Presents an activity in which students collect and organize data from a real-world simulation of the scientific concept of half life. Students collect data using a marble sifter, analyze the data using a graphing calculator, and determine an appropriate mathematical model. Includes reproducible worksheets. (MDH)

  9. Active music therapy and Parkinson's disease: methods.

    PubMed

    Pacchetti, C; Aglieri, R; Mancini, F; Martignoni, E; Nappi, G

    1998-01-01

    Music therapy (MT) is an unconventional, multisensorial therapy poorly assessed in medical care but widely used to different ends in a variety of settings. MT has two branches: active and passive. In active MT the utilisation of instruments is structured to correspond to all sensory organs so as to obtain suitable motor and emotional responses. We conducted a prospective study to evaluate the effects of MT in the neurorehabilitation of patients with Parkinson's Disease (PD), a common degenerative disorder involving movement and emotional impairment. Sixteen PD patients took part in 13 weekly sessions of MT each lasting 2 hours. At the beginning and at the end of the session, every 2 weeks, the patients were evaluated by a neurologist, who assessed PD severity with UPDRS, emotional functions with Happiness Measures (HM) and quality of life using the Parkinson's Disease Quality of Life Questionnaire (PDQL). After every session a significant improvement in motor function, particularly in relation to hypokinesia, was observed both in the overall and in the pre-post session evaluations. HM, UPDRS-ADL and PDQL changes confirmed an improving effect of MT on emotional functions, activities of daily living and quality of life. In conclusion, active MT, operating at a multisensorial level, stimulates motor, affective and behavioural functions. Finally, we propose active MT as new method to include in PD rehabilitation programmes. This article describes the methods adopted during MT sessions with PD patients.

  10. Graves' disease: thyroid function and immunologic activity

    SciTech Connect

    Gossage, A.A.; Crawley, J.C.; Copping, S.; Hinge, D.; Himsworth, R.L.

    1982-11-01

    Patients with Graves' disease were studied for two years during and after a twelve-month course of treatment. Disease activity was determined by repeated measurements of thyroidal uptake of (/sup 99m/Tc)pertechnetate during tri-iodothyronine administration. These in-vivo measurements of thyroid stimulation were compared with the results of in-vitro assays of Graves, immunoglobulin (TSH binding inhibitory activity--TBIA). There was no correlation between the thyroid uptake and TBIA on diagnosis. Pertechnetate uptake and TBIA both declined during the twelve months of antithyroid therapy. TBIA was detectable in sera from 19 of the 27 patients at diagnosis; in 11 of these 19 patients there was a good correlation (p less than 0.05) throughout the course of their disease between the laboratory assay of the Graves, immunoglobulin and the thyroid uptake. Probability of recurrence can be assessed but sustained remission of Graves' disease after treatment cannot be predicted from either measurement alone or in combination.

  11. Complement activation in very early Alzheimer disease.

    PubMed

    Zanjani, H; Finch, C E; Kemper, C; Atkinson, J; McKeel, D; Morris, J C; Price, J L

    2005-01-01

    The activation of the classical complement (C)-system in early-stage Alzheimer disease (AD) and nondemented aging was examined with immunohistochemistry in subjects assessed by the Clinical Dementia Rating (CDR). Activation (staining for C3 and C4 fragments) was found in all brains with amyloid deposits, including all nondemented (CDR 0) cases, with either small numbers of diffuse plaques or with sufficient plaques and tangles to indicate preclinical AD. Staining for C3 and C4 increased in parallel with plaque density in very mild to severe clinical AD. A subset of very mild AD (CDR 0.5) cases also showed C1q (on plaques) and C5b-9 (on neuritic plaques and tangles), whereas these C-fragments were consistently found in severe AD (CDR 3). Mirror section (split-face) analysis showed that C1q, C3, and apoJ (clusterin) occurred on the same plaques. However, C-system regulators CD59, CR1, DAF, and MCP were not detected on plaques or tangles at any stage, indicating that C-activation related to AD is incompletely controlled.

  12. Circulating immune complexes and disease activity in Crohn's disease.

    PubMed Central

    Fiasse, R; Lurhuma, A Z; Cambiaso, C L; Masson, P L; Dive, C

    1978-01-01

    Circulating immune complexes were determined in 59 consecutive patients with Crohn's disease and 100 blood donors by a double method based on the inhibition of the agglutinating activity of CIq and/or rheumatoid factor on the IgG-coated polystyrene particles. In patients, the incidence of positive immune complexes was 63% and 61% at first testing, 85% and 78% at subsequent determinations; there was a good correlation between the inhibition titres of CIq and those of rheumatoid factor (p less than 0.001). In blood donors, the incidence was 22% and 14% at low titre. The incidence of immune complexes was the lowest (36%) in the group of resected patients without signs of relapse; repeat determinations showed absence of immune complexes three months postoperatively. In patients medically treated for primary disease or relapse, rheumatoid factor titre higher than 1/1 was less frequent than in medically untreated patients with active disease (p less than 0.01). A significantly higher concentration of serum alpha-1-antitrypsin and orosomucoid, and a significantly lower level of serum iron were found in patients with an IC titre exceeding 1/1; longitudinal studies showed in most cases a concordance between the evolution of immune complex titres, inflammatory parameters and clinical status. PMID:308030

  13. Germ Smart: Children's Activities in Disease Prevention.

    ERIC Educational Resources Information Center

    Scheer, Judith K.

    This booklet is part of the "Children's Activity Series," a set of four supplemental teaching resources that promote awareness about health, family life, and cultural diversity for children in kindergarten through third grade. Nine activities are included in this booklet to help children be "germ smart" help children in kindergarten through third…

  14. Noninvasive Markers of Disease Activity in Inflammatory Bowel Disease

    PubMed Central

    Kane, Sunanda

    2014-01-01

    It is often difficult to assess disease activity in inflammatory bowel disease (IBD). Noninvasive biomarkers are a means of quantifying often nebulous symptoms without subjecting patients to endoscopy or radiation. This paper highlights markers present in feces, serum, or urine that have all been compared with the gold standard, histologic analysis of endoscopically collected specimens. Two categories of markers are featured: well-researched markers of mucosal inflammation with high sensitivity and specificity (calprotectin, lactoferrin, and S100A12) and novel promising markers, some of which are already clinically employed for reasons unrelated to IBD (interleukin [IL]-17, IL-33/ST2, adenosine deaminase, polymorphonuclear elastase, matrix metalloproteinase-9, neopterin, serum M30, and fecal immunohistochemistry). The data pertaining to the more-established markers are intended to highlight recent clinical applications for these markers (ie, assessing disease outside of the colon or in the pediatric population as well as being a cost-saving alternative to colonoscopy to screen for IBD). As there is no evidence to date that a specific marker will accurately be able to represent the entire IBD patient population, it is likely that a combination of the existing markers will be most clinically relevant to the practicing gastroenterologist attempting to evaluate disease severity in a specific patient. Familiarity with the most promising emerging markers will allow a better understanding of new studies and their impact on patient care. PMID:27551251

  15. The development of the disease activity score (DAS) and the disease activity score using 28 joint counts (DAS28).

    PubMed

    van Riel, P L C M

    2014-01-01

    In rheumatoid arthritis, disease activity cannot be measured using a single variable. The Disease Activity Score (DAS) has been developed as a quantitative index to be able to measure, study and manage disease activity in RA in daily clinical practice, clinical trials, and long term observational studies. The DAS is a continuous measure of RA disease activity that combines information from swollen joints, tender joints, acute phase response and patient self-report of general health. Cut points were developed to classify patients in remission, as well as low, moderate, and severe disease activity in the 1990s. DAS-based EULAR response criteria were primarily developed to be used in clinical trials to classify individual patients as non-, moderate, or good responders, depending on the magnitude of change and absolute level of disease activity at the conclusion of the test.

  16. Remote Physical Activity Monitoring in Neurological Disease: A Systematic Review

    PubMed Central

    Block, Valerie A. J.; Pitsch, Erica; Tahir, Peggy; Cree, Bruce A. C.; Allen, Diane D.; Gelfand, Jeffrey M.

    2016-01-01

    Objective To perform a systematic review of studies using remote physical activity monitoring in neurological diseases, highlighting advances and determining gaps. Methods Studies were systematically identified in PubMed/MEDLINE, CINAHL and SCOPUS from January 2004 to December 2014 that monitored physical activity for ≥24 hours in adults with neurological diseases. Studies that measured only involuntary motor activity (tremor, seizures), energy expenditure or sleep were excluded. Feasibility, findings, and protocols were examined. Results 137 studies met inclusion criteria in multiple sclerosis (MS) (61 studies); stroke (41); Parkinson's Disease (PD) (20); dementia (11); traumatic brain injury (2) and ataxia (1). Physical activity levels measured by remote monitoring are consistently low in people with MS, stroke and dementia, and patterns of physical activity are altered in PD. In MS, decreased ambulatory activity assessed via remote monitoring is associated with greater disability and lower quality of life. In stroke, remote measures of upper limb function and ambulation are associated with functional recovery following rehabilitation and goal-directed interventions. In PD, remote monitoring may help to predict falls. In dementia, remote physical activity measures correlate with disease severity and can detect wandering. Conclusions These studies show that remote physical activity monitoring is feasible in neurological diseases, including in people with moderate to severe neurological disability. Remote monitoring can be a psychometrically sound and responsive way to assess physical activity in neurological disease. Further research is needed to ensure these tools provide meaningful information in the context of specific neurological disorders and patterns of neurological disability. PMID:27124611

  17. Early detection of thrombin activity in neuroinflammatory disease

    PubMed Central

    Davalos, Dimitrios; Baeten, Kim M; Whitney, Michael A; Mullins, Eric S; Friedman, Beth; Olson, Emilia S; Ryu, Jae Kyu; Smirnoff, Dimitri S; Petersen, Mark A; Bedard, Catherine; Degen, Jay L; Tsien, Roger Y; Akassoglou, Katerina

    2014-01-01

    Although multiple sclerosis (MS) has been associated with the coagulation system, the temporal and spatial regulation of coagulation activity in neuroinflammatory lesions is unknown. Using a novel molecular probe, we characterized the activity pattern of thrombin, the central protease of the coagulation cascade, in experimental autoimmune encephalomyelitis. Thrombin activity preceded onset of neurological signs, increased at disease peak, and correlated with fibrin deposition, microglial activation, demyelination, axonal damage, and clinical severity. Mice with a genetic deficit in prothrombin confirmed the specificity of the thrombin probe. Thrombin activity might be exploited for developing sensitive probes for preclinical detection and monitoring of neuroinflammation and MS progression. PMID:24740641

  18. Non-Invasive Molecular Imaging of Disease Activity in Atherosclerosis

    PubMed Central

    Dweck, Marc R; Aikawa, Elena; Newby, David E; Tarkin, Jason; Rudd, James; Narula, Jagat; Fayad, Zahi A.

    2016-01-01

    Major focus has been placed on the identification of vulnerable plaques as a means of improving the prediction of myocardial infarction. However, this strategy has recently been questioned on the basis that the majority of these individual coronary lesions do not in fact go on to cause clinical events. Attention is therefore shifting to alternative imaging modalities that might provide a more complete pan-coronary assessment of the atherosclerotic disease process. These include markers of disease activity with the potential to discriminate between patients with stable burnt-out disease that is no longer metabolically active and those with active atheroma, faster disease progression and increased risk of infarction. This review will examine how novel molecular imaging approaches can provide such assessments, focusing on inflammation and microcalcification activity, the importance of these processes to coronary atherosclerosis and the advantages and challenges posed by these techniques. PMID:27390335

  19. 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

  20. Low serum alkaline phosphatase activity in Kikuchi-Fujimoto disease

    PubMed Central

    Inamo, Yasuji

    2017-01-01

    Abstract Various laboratory findings are helpful in making a diagnosis of Kikuchi-Fujimoto disease (KFD); however, they are not specific. We found decreased serum alkaline phosphatase (SAP) activity in children with KFD. The levels of SAP fell in the acute phase and recovered during convalescence. We conclude that low SAP activity is a characteristic of KFD and may be an auxiliary diagnostic marker for the disease. PMID:28248884

  1. [Problems connected with sexual activity in patients with heart disease].

    PubMed

    Rembek, Magdalena; Tylkowski, Michał; Piestrzeniewicz, Katarzyna; Goch, Jan Henryk

    2007-08-01

    The paper presents some basic data on sexual activity in patients with heart disease. The most typical problems of people with stable angina or after myocardial infarction connected with sexual intercourse have been presented. Modulation of risk of heart attack during sexual activity and main problems of sexual dysfunction after acute coronary syndromes have been described.

  2. Neuropathologic correlates of activities of daily living in Alzheimer disease.

    PubMed

    Marshall, Gad A; Fairbanks, Lynn A; Tekin, Sibel; Vinters, Harry V; Cummings, Jeffrey L

    2006-01-01

    Functional status, reflected by measures of activities of daily living (ADLs), deteriorates as Alzheimer disease (AD) progresses. Decline in activities of daily living may be mediated by executive and frontal lobe dysfunction. The objective of this study was to examine the relationship between activities of daily living and pathologic burden in Alzheimer disease. Twenty two subjects with definite Alzheimer disease were selected from the UCLA ADRC neuropathology database. A total activities of daily living score was derived from the Retrospective Collateral Dementia Interview-Revised (RCDI-R) questionnaire, which was administered to caregivers of autopsied subjects included in the study. Neuritic plaque (NP) and neurofibrillary tangle (NFT) counts were performed for 8 brain regions. There was a significant positive correlation between total activities of daily living score (higher scores indicate more disability) and mean neuritic plaques and neurofibrillary tangle counts (r = 0.671, P = 0.001, and r = 0.542, P = 0.009, resp), as well as CA1 and prosubiculum neuritic plaques and neurofibrillary tangle counts, right and left orbital frontal neuritic plaques counts, and occipital neuritic plaques count. Total activities of daily living score did not correlate with age at death, age at symptom onset, dementia duration, gender, or education. Deteriorating activities of daily living in Alzheimer Disease subjects correlate with greater overall pathologic burden and possibly selectively with involvement of the medial temporal, occipital, and orbital frontal regions.

  3. Physical activity and coronary heart disease.

    PubMed

    Froelicher, V; Battler, A; McKirnan, M D

    1980-01-01

    This review deals with more recent investigations of the health benefit of regular aerobic exercise including studies in: epidemiology, echocardiography, animal research, and cardiac rehabilitation. Recent epidemiological studies support the preventative aspects of exercise in apparently healthy individuals. Echocardiographic studies suggest morphologic changes in young individuals. Recent animal research confirms previous results as well as documenting improvment in cardiac function even under hypoxic and ischemic conditions. Studies of cardiac rehabilitation suggest that medically supervised programs do not improve or worsen morbidity and mortality. The question of whether exercise training can cause cardiac effects in patients with coronary disease rather than just improve the response of the peripheral circulation to exercise may be answered using newer radionuclide techniques.

  4. Epileptic activity in Alzheimer's disease: causes and clinical relevance.

    PubMed

    Vossel, Keith A; Tartaglia, Maria C; Nygaard, Haakon B; Zeman, Adam Z; Miller, Bruce L

    2017-04-01

    Epileptic activity is frequently associated with Alzheimer's disease; this association has therapeutic implications, because epileptic activity can occur at early disease stages and might contribute to pathogenesis. In clinical practice, seizures in patients with Alzheimer's disease can easily go unrecognised because they usually present as non-motor seizures, and can overlap with other symptoms of the disease. In patients with Alzheimer's disease, seizures can hasten cognitive decline, highlighting the clinical relevance of early recognition and treatment. Some evidence indicates that subclinical epileptiform activity in patients with Alzheimer's disease, detected by extended neurophysiological monitoring, can also lead to accelerated cognitive decline. Treatment of clinical seizures in patients with Alzheimer's disease with select antiepileptic drugs (AEDs), in low doses, is usually well tolerated and efficacious. Moreover, studies in mouse models of Alzheimer's disease suggest that certain classes of AEDs that reduce network hyperexcitability have disease-modifying properties. These AEDs target mechanisms of epileptogenesis involving amyloid β and tau. Clinical trials targeting network hyperexcitability in patients with Alzheimer's disease will identify whether AEDs or related strategies could improve their cognitive symptoms or slow decline.

  5. Daily ambulatory activity levels in idiopathic Parkinson disease.

    PubMed

    Skidmore, Frank M; Mackman, Chad A; Pav, Breckon; Shulman, Lisa M; Garvan, Cyndi; Macko, Richard F; Heilman, Kenneth M

    2008-01-01

    Patients with Parkinson disease (PD) may have decreased physical activity due to motor deficits. We recently validated the reliability of step activity monitors (SAMs) to accurately count steps in PD, and we wished to use them to evaluate the impact of disease severity on home activity levels in PD. Twenty-six subjects with PD (Hoehn and Yahr disease stage 2-4) were recruited to participate in a study of activity levels over 48 hours. Ability to achieve 95% device accuracy was an entry requirement. A Unified Parkinson Disease Rating Scale (UPDRS) evaluation was performed on all subjects, subjects were monitored for 48 hours, and total number of steps per day and maximum steps taken per hour were calculated. Out of 26 subjects, 25 met entry requirements. We calculated the number of steps taken per day, as well as maximal activity levels, and correlated these with UPDRS total score, the activity of daily living subscale, and the UPDRS motor function subscale off and on medication (all p < 0.01). Transition from Hoehn and Yahr stage 2 to stage 3 was associated with a decline in functional mobility (p < 0.005). A microprocessor-linked SAM accurately counted steps in subjects with PD. The number of steps taken correlated highly with disease severity. SAMs may be useful outcome measures in PD.

  6. Levodopa influences striatal activity but does not affect cortical hyper-activity in Parkinson's disease.

    PubMed

    Martinu, K; Degroot, C; Madjar, C; Strafella, A P; Monchi, O

    2012-02-01

    Motor studies of Parkinson's disease (PD) have shown cortical hypo-activity in relation to nigrostriatal dopamine depletion. Cognitive studies also identified increased cortical activity in PD. We have previously suggested that the hypo-activity/hyper-activity patterns observed in PD are related to the striatal contribution. Tasks that recruit the striatum in control participants are associated with cortical hypo-activity in patients with PD, whereas tasks that do not result in cortical hyper-activity. The putamen, a structure affected by the neurodegeneration observed in PD, shows increased activation for externally-triggered (ET) and self-initiated (SI) movements. The first goal of this study was to evaluate the effect of levodopa on the putamen's response to ET and SI movements. Our second goal was to assess the effect of levodopa on the hypo-activity/hyper-activity patterns in cortical areas. Patients with PD on and off levodopa and healthy volunteers performed SI, ET and control finger movements during functional magnetic resonance imaging. Healthy participants displayed significant differences in putamen activity in ET and SI movements. These differences were reduced in patients off medication, with non-task-specific increases in activity after levodopa administration. Furthermore, the ventrolateral prefrontal cortex showed significant increases in activity during SI movements in healthy controls, whereas it was hypo-active in PD. This region showed significantly increased activity during ET movements in patients off medication. Levodopa had no effect on this discrepancy. Our results suggest that dopamine replacement therapy has a non-task-specific effect on motor corticostriatal regions, and support the hypothesis that increases and decreases in cortical activity in PD are related to the mesocortical dopamine pathway imbalance.

  7. 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

  8. Microscopic features for initial diagnosis and disease activity evaluation in inflammatory bowel disease.

    PubMed

    Bressenot, Aude; Geboes, Karel; Vignaud, Jean-Michel; Guéant, Jean-Louis; Peyrin-Biroulet, Laurent

    2013-07-01

    Inflammatory bowel disease is characterized by 2 major entities: Crohn's disease (CD) and ulcerative colitis (UC). In clinical practice, separation of UC and CD has been based on a variety of clinical features, symptoms, endoscopic and radiological, gross and microscopic characteristics. The microscopic diagnosis of inflammatory bowel disease is based on a combination of 2 types of lesions: architectural abnormalities and inflammatory features. However, microscopic distinction between these 2 entities can be difficult and often results in an interim diagnosis of "indeterminate colitis." Recommendations are made to encourage pathologists to give an indication of the activity of the disease: in UC, biopsies are used to discriminate between quiescent disease, inactive disease, and different grades of activity; in CD, evaluation of disease activity is limited and inactivity in the biopsy may not reflect inactivity in the patient. The aim of this review was to summarize microscopic features of inflammatory bowel disease for initial diagnosis and evaluation of disease activity in both CD and UC.

  9. Glucocerebrosidase activity in Parkinson's disease with and without GBA mutations.

    PubMed

    Alcalay, Roy N; Levy, Oren A; Waters, Cheryl C; Fahn, Stanley; Ford, Blair; Kuo, Sheng-Han; Mazzoni, Pietro; Pauciulo, Michael W; Nichols, William C; Gan-Or, Ziv; Rouleau, Guy A; Chung, Wendy K; Wolf, Pavlina; Oliva, Petra; Keutzer, Joan; Marder, Karen; Zhang, Xiaokui

    2015-09-01

    Glucocerebrosidase (GBA) mutations have been associated with Parkinson's disease in numerous studies. However, it is unknown whether the increased risk of Parkinson's disease in GBA carriers is due to a loss of glucocerebrosidase enzymatic activity. We measured glucocerebrosidase enzymatic activity in dried blood spots in patients with Parkinson's disease (n = 517) and controls (n = 252) with and without GBA mutations. Participants were recruited from Columbia University, New York, and fully sequenced for GBA mutations and genotyped for the LRRK2 G2019S mutation, the most common autosomal dominant mutation in the Ashkenazi Jewish population. Glucocerebrosidase enzymatic activity in dried blood spots was measured by a mass spectrometry-based assay and compared among participants categorized by GBA mutation status and Parkinson's disease diagnosis. Parkinson's disease patients were more likely than controls to carry the LRRK2 G2019S mutation (n = 39, 7.5% versus n = 2, 0.8%, P < 0.001) and GBA mutations or variants (seven homozygotes and compound heterozygotes and 81 heterozygotes, 17.0% versus 17 heterozygotes, 6.7%, P < 0.001). GBA homozygotes/compound heterozygotes had lower enzymatic activity than GBA heterozygotes (0.85 µmol/l/h versus 7.88 µmol/l/h, P < 0.001), and GBA heterozygotes had lower enzymatic activity than GBA and LRRK2 non-carriers (7.88 µmol/l/h versus 11.93 µmol/l/h, P < 0.001). Glucocerebrosidase activity was reduced in heterozygotes compared to non-carriers when each mutation was compared independently (N370S, P < 0.001; L444P, P < 0.001; 84GG, P = 0.003; R496H, P = 0.018) and also reduced in GBA variants associated with Parkinson's risk but not with Gaucher disease (E326K, P = 0.009; T369M, P < 0.001). When all patients with Parkinson's disease were considered, they had lower mean glucocerebrosidase enzymatic activity than controls (11.14 µmol/l/h versus 11.85 µmol/l/h, P = 0.011). Difference compared to controls persisted in patients with

  10. 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.

  11. Biomarkers of endothelial activation/dysfunction in infectious diseases

    PubMed Central

    Page, Andrea V; Liles, W Conrad

    2013-01-01

    Endothelial dysfunction contributes to the pathogenesis of a variety of potentially serious infectious diseases and syndromes, including sepsis and septic shock, hemolytic-uremic syndrome, severe malaria, and dengue hemorrhagic fever. Because endothelial activation often precedes overt endothelial dysfunction, biomarkers of the activated endothelium in serum and/or plasma may be detectable before classically recognized markers of disease, and therefore, may be clinically useful as biomarkers of disease severity or prognosis in systemic infectious diseases. In this review, the current status of mediators of endothelial cell function (angiopoietins-1 and -2), components of the coagulation pathway (von Willebrand Factor, ADAMTS13, and thrombomodulin), soluble cell-surface adhesion molecules (soluble E-selectin, sICAM-1, and sVCAM-1), and regulators of vascular tone and permeability (VEGF and sFlt-1) as biomarkers in severe infectious diseases is discussed in the context of sepsis, E. coli O157:H7 infection, malaria, and dengue virus infection. PMID:23669075

  12. Data mining for correlations between diet and Crohn's disease activity.

    PubMed

    Cooper, Jason G; Purcell, Gretchen P

    2006-01-01

    Crohn's disease is a debilitating condition that affects the entire gastrointestinal tract and often requires aggressive and invasive therapies. Several studies have suggested dietary triggers for disease activity. We have created a web-based tool to allow participants to record both daily food intake and wellness (i.e., disease-specific quality of life). We seek to determine if measurable correlations exist between these events in patients with Crohn's disease. Advanced data mining techniques are employed to find such correlations and the efficacies of chosen techniques are assessed. We tested our web-based system in a pilot study involving 7 participants, and we found that traditional statistical techniques identified diet and disease activity correlations in short-term data sets.

  13. BACE1 and BACE2 enzymatic activities in Alzheimer's disease.

    PubMed

    Ahmed, Rachel R; Holler, Christopher J; Webb, Robin L; Li, Feng; Beckett, Tina L; Murphy, M Paul

    2010-02-01

    beta-Secretase is the rate limiting enzymatic activity in the production of the amyloid-beta peptide (Abeta) and is thought to be involved in Alzheimer's disease (AD) pathogenesis. Although BACE1 (beta-site APP Cleaving Enzyme 1, EC 3.4.23.46) has received significant attention, the related BACE2 (EC 3.4.23.45) has not. Though BACE2 is also expressed in the brain, its potential role in AD has not been resolved. In this study, we compared the activities of both BACE1 and BACE2, which were isolated from the same samples of frontal cortex from both AD-affected individuals and age-matched controls. BACE1 activity showed a significant positive correlation with the amount of extractable Abeta, and BACE1 protein and activity were significantly increased in AD cases. Unexpectedly, there were substantial total amounts of BACE2 protein and enzymatic activity in the human brain. BACE2 activity did not change significantly in the AD brain, and was not related to Abeta concentration. These data indicate that BACE1 likely accounts for most of the Abeta produced in the human brain, and that BACE2 activity is not a likely contributor. However, as both forms of BACE compete for the same substrate pool, even small changes in BACE2 activity could have consequences for human disease.

  14. EULAR Sjogren's syndrome disease activity index: development of a consensus systemic disease activity index for primary Sjogren's syndrome

    PubMed Central

    Seror, Raphaèle; Ravaud, Philippe; Bowman, Simon; Baron, Gabriel; Tzioufas, Athanasios; Theander, Elke; Gottenberg, Jacques-Eric; Bootsma, Hendrika; Mariette, Xavier; Vitali, Claudio

    2010-01-01

    Objective To develop a disease activity index for patients with primary Sjögren’s syndrome (SS): the European League Against Rheumatism (EULAR) Sjögren’s Syndrome Disease Activity Index (ESSDAI). Methods Thirty-nine SS experts participated in an international collaboration, promoted by EULAR, to develop the ESSDAI. Experts identified 12 organ-specific “domains” contributing to disease activity. For each domain, features of disease activity were classified in 3 or 4 levels according to their severity. Data abstracted from 96 patients with systemic complications of primary SS were used to generate 702 realistic vignettes for which all possible systemic complications were represented. Using the 0–10 physician global assessment (PhGA) scale, each expert scored the disease activity of 5 patient profiles and 20 realistic vignettes. Multiple regression modelling, with PhGA used as the dependent variable, was used to estimate the weight of each domain. Results All 12 domains were significantly associated with disease activity in the multivariate model, domain weights ranged from 1 to 6. The ESSDAI scores varied from 2 to 47 and were significantly correlated with PhGA for both real patient profiles and realistic vignettes (r=0.61 and r=0.58, respectively, p<0.0001). Compared to 57 (59.4%) of the real patient profiles, 468 (66.7%) of the realistic vignettes were considered likely or very likely to be true. Conclusion The ESSDAI is a clinical index designed to measure disease activity in patients with primary SS. Once validated, such a standardized evaluation of primary SS should facilitate clinical research and should be helpful as an outcome measure in clinical trials. PMID:19561361

  15. Ramiprilate inhibits functional matrix metalloproteinase activity in Crohn's disease fistulas.

    PubMed

    Efsen, Eva; Saermark, Torben; Hansen, Alastair; Bruun, Eywin; Brynskov, Jørn

    2011-09-01

    Increased expression of matrix metalloproteinase (MMP)-2, -3 and -9 has been demonstrated in Crohn's disease fistulas, but it is unknown whether these enzymes are biologically active and represent a therapeutic target. Therefore, we investigated the proteolytic activity of MMPs in fistula tissue and examined the effect of inhibitors, including clinically available drugs that beside their main action also suppress MMPs. Fistula specimens were obtained by surgical excision from 22 patients with Crohn's disease and from 10 patients with fistulas resulting from other causes. Colonic endoscopic biopsies from six controls were also included. Total functional MMP activity was measured by a high-pressure liquid chromatography (HPLC)-based, fluorogenic MMP-substrate cleavage assay, and the specific activity of MMP-2, -3 and -9 by the MMP Biotrak Activity Assay. The MMP inhibitors comprised ethylene-diamine-tetraacetic acid (EDTA), the synthetic broad-spectrum inhibitor, GM6001, the angiotensin-converting enzyme (ACE) inhibitor, ramiprilate, and the tetracycline, doxycycline. In Crohn's disease fistulas, about 50% of the total protease activity was attributable to MMP activity. The average total MMP activity was significantly higher (about 3.5-times) in Crohn's fistulas (471 FU/μg protein, range 49-2661) compared with non-Crohn's fistulas [134 FU/μg protein, range 0-495, (p < 0.05)] and normal colon [153 FU/μg protein, range 77-243, (p < 0.01)]. MMP-3 activity was increased in Crohn's fistulas (1.4 ng/ml, range 0-9.83) compared with non-Crohn's fistulas, [0.32 ng/ml, range 0-2.66, (p < 0.02)]. The same applied to MMP-9 activity [0.64 ng/ml, range 0-5.66 and 0.17 ng/ml, range 0-1.1, respectively (p < 0.04)]. Ramiprilate significantly decreased the average total MMP activity level by 42% and suppressed the specific MMP-3 activity by 72%, which is comparable to the effect of GM6001 (87%). Moreover, MMP-9 activity was completely blunted by ramiprilate. Doxycycline had no

  16. Activation of AMP-activated kinase as a strategy for managing autosomal dominant polycystic kidney disease.

    PubMed

    McCarty, Mark F; Barroso-Aranda, Jorge; Contreras, Francisco

    2009-12-01

    There is evidence that overactivity of both mammalian target of rapamycin (mTOR) and cystic fibrosis transmembrane conductance regulator (CFTR) contributes importantly to the progressive expansion of renal cysts in autosomal dominant polycystic kidney disease (ADPKD). Recent research has established that AMP-activated kinase (AMPK) can suppress the activity of each of these proteins. Clinical AMPK activators such as metformin and berberine may thus have potential in the clinical management of ADPKD. The traditional use of berberine in diarrhea associated with bacterial infections may reflect, in part, the inhibitory impact of AMPK on chloride extrusion by small intestinal enterocytes.

  17. An exploratory study of activity in veterans with Parkinson's disease.

    PubMed

    Trail, Marilyn; Petersen, Nancy J; Nelson, Naomi; Lai, Eugene C

    2012-08-01

    Movement disorder specialists have limited information on the specifics of how patients with Parkinson’s disease (PD) spend their time. We deemed it important to examine the relationships among activity and daily energy expenditure (DEE), non-motor symptoms, and body mass index in veterans with PD who were outpatients at a Veterans Affairs medical center. In this exploratory study, we mailed demographic and activity questionnaires and gathered data on 100 patients. Activity was categorized into five domains and three intensity levels, and DEE was measured in kilocalories. Light activities accounted for 64.9% of DEE (9.1 h), moderate activities for 32.9% (2.1 h), and vigorous activities for 2.2% (0.1 h) of DEE. Television viewing comprised 10.6% (2.5 h) of the day. The effects of non-motor symptoms were significantly associated with more time spent on activities of daily life (ADL). Patients rated fatigue and pain as having the greatest impact on their daily activities. The overweight/obese group of PD patients expended more overall DEE (p = 0.044) and more DEE on social activities (p = 0.024) and light intensity activities (p = 0.021) than did the underweight/normal group. Leisure activities for both groups changed from active to passive. Veterans with PD primarily expended DEE on ADL, TV viewing, and light intensity activities. Television viewing time may have been under reported. Movement disorder specialists can be more proactive in referring patients to physical therapy and encouraging their participation in community exercise and support groups.

  18. Type-1 cannabinoid receptor activity during Alzheimer's disease progression.

    PubMed

    Manuel, Iván; González de San Román, Estíbaliz; Giralt, M Teresa; Ferrer, Isidro; Rodríguez-Puertas, Rafael

    2014-01-01

    The activity of CB1 cannabinoid receptors was studied in postmortem brain samples of Alzheimer's disease (AD) patients during clinical deterioration. CB1 activity was higher at earlier AD stages in limited hippocampal areas and internal layers of frontal cortex, but a decrease was observed at the advanced stages. The pattern of modification appears to indicate initial hyperactivity of the endocannabinoid system in brain areas that lack classical histopathological markers at earlier stages of AD, indicating an attempt to compensate for the initial synaptic impairment, which is then surpassed by disease progression. These results suggest that initial CB1 stimulation might have therapeutic relevance.

  19. Physical activity and neuropsychiatric symptoms of Parkinson disease.

    PubMed

    Abrantes, Ana M; Friedman, Joseph H; Brown, Richard A; Strong, David R; Desaulniers, Julie; Ing, Eileen; Saritelli, Jennifer; Riebe, Deborah

    2012-09-01

    Neuropsychiatric symptoms of Parkinson disease (PD) such as fatigue, depression, and apathy are common and detract from quality of life. There is little published on the impact of physical activity on the neuropsychiatric symptoms of PD. A convenience sample of 45 patients with PD (mean age = 66.1 years; 33% female) completed questionnaires on physical activity, neuropsychiatric symptoms, and specific exercise preferences. Covarying for age and gender, higher levels of physical activity were associated with significantly less fatigue, as well as a trend for less apathy and depression and greater positive affect. Exercise preferences included moderate intensity (73%), at home (56%), in the morning (73%), scheduled (69%), options for varied activities (73%), and preference for both structured/supervised (50%), and unsupervised/self-paced (50%) programs. Preferred activities included the use of aerobic exercise equipment, resistance training, and yoga. Developing and tailoring exercise programs that incorporate specific preferences may result in more effective interventions for patients with PD.

  20. Linking estrogen receptor β expression with inflammatory bowel disease activity

    PubMed Central

    Pierdominici, Marina; Maselli, Angela; Varano, Barbara; Barbati, Cristiana; Cesaro, Paola; Spada, Cristiano; Zullo, Angelo; Lorenzetti, Roberto; Rosati, Marco; Rainaldi, Gabriella; Limiti, Maria Rosaria; Guidi, Luisa

    2015-01-01

    Crohn disease (CD) and ulcerative colitis (UC) are chronic forms of inflammatory bowel disease (IBD) whose pathogenesis is only poorly understood. Estrogens have a complex role in inflammation and growing evidence suggests that these hormones may impact IBD pathogenesis. Here, we demonstrated a significant reduction (p < 0.05) of estrogen receptor (ER)β expression in peripheral blood T lymphocytes from CD/UC patients with active disease (n = 27) as compared to those in remission (n = 21) and healthy controls (n = 29). Accordingly, in a subgroup of CD/UC patients undergoing to anti-TNF-α therapy and responsive to treatment, ERβ expression was higher (p < 0.01) than that observed in not responsive patients and comparable to that of control subjects. Notably, ERβ expression was markedly decreased in colonic mucosa of CD/UC patients with active disease, reflecting the alterations observed in peripheral blood T cells. ERβ expression inversely correlated with interleukin (IL)-6 serum levels and exogenous exposure of both T lymphocytes and intestinal epithelial cells to this cytokine resulted in ERβ downregulation. These results demonstrate that the ER profile is altered in active IBD patients at both mucosal and systemic levels, at least in part due to IL-6 dysregulation, and highlight the potential exploitation of T cell-associated ERβ as a biomarker of endoscopic disease activity. PMID:26497217

  1. Recreational physical activity and risk of Parkinson's disease.

    PubMed

    Thacker, Evan L; Chen, Honglei; Patel, Alpa V; McCullough, Marjorie L; Calle, Eugenia E; Thun, Michael J; Schwarzschild, Michael A; Ascherio, Alberto

    2008-01-01

    The purpose of this study was to investigate associations between recreational physical activity and Parkinson's disease (PD) risk. We prospectively followed 143,325 participants in the Cancer Prevention Study II Nutrition Cohort from 1992 to 2001 (mean age at baseline = 63). Recreational physical activity was estimated at baseline from the reported number of hours per week on average spent performing light intensity activities (walking, dancing) and moderate to vigorous intensity activities (jogging/running, lap swimming, tennis/racquetball, bicycling/stationary bike, aerobics/calisthenics). Incident cases of PD (n = 413) were confirmed by treating physicians and medical record review. Relative risks (RR) were estimated using proportional hazards models, adjusting for age, gender, smoking, and other risk factors. Risk of PD declined in the highest categories of baseline recreational activity. The RR comparing the highest category of total recreational activity (men > or = 23 metabolic equivalent task-hours/week [MET-h/wk], women > or = 18.5 MET-h/wk) to no activity was 0.8 (95% CI: 0.6, 1.2; P trend = 0.07). When light activity and moderate to vigorous activity were examined separately, only the latter was found to be associated with PD risk. The RR comparing the highest category of moderate to vigorous activity (men > or = 16 MET-h/wk, women > or = 11.5 MET-h/wk) to the lowest (0 MET-h/wk) was 0.6 (95% CI: 0.4, 1.0; P trend = 0.02). These results did not differ significantly by gender. The results were similar when we excluded cases with symptom onset in the first 4 years of follow-up. Our results may be explained either by a reduction in PD risk through moderate to vigorous activity, or by decreased baseline recreational activity due to preclinical PD.

  2. Proliferating activity in paget disease of the nipple.

    PubMed

    Noel, Jean-Christophe; Fayt, Isabelle; Buxant, Frederic

    2010-03-01

    Paget disease of the nipple is a rare disease characterized by the presence of malignant glandular cells within the squamous epithelium of the nipple. The most common hypothesis to explain the development of Paget disease is an intraepithelial epidermotropic migration of malignant epithelial cells originating from an underlying intraductal carcinoma. If the immunohistochemical properties of the Paget cells in the nipple have been extensively studied, their proliferating characteristics remain paradoxically poorly studied. In the present study we have investigated the proliferating activity of Paget cells in the nipple by using double stain immunohistochemistry with both Ki67 (a protein which is expressed in all active parts of the cell cycle) and cytokeratin 7 (a highly sensitive marker of Paget cells). Ten cases of Paget disease and in their associated intraductal carcinomas (n = 10) and/or invasive carcinomas (n = 4) were tested. The mean Ki67 index was in Paget disease (26% +/- 10), in intraductal carcinomas (23% +/- 8) and/or in invasive carcinomas (20% +/- 8) (p > 0,05). This is the first report to convincingly demonstrate by specific double stain immunohistochemistry that Paget disease and underlying intraductal carcinomas share a close proliferating activity.

  3. Hyperosmotic activation of CNS sympathetic drive: implications for cardiovascular disease

    PubMed Central

    Toney, Glenn M; Stocker, Sean D

    2010-01-01

    Evidence now indicates that exaggerated sympathetic nerve activity (SNA) significantly contributes to salt-sensitive cardiovascular diseases. Although CNS mechanisms that support the elevation of SNA in various cardiovascular disease models have been intensively studied, many mechanistic details remain unknown. In recent years, studies have shown that SNA can rise as a result of both acute and chronic increases of body fluid osmolality. These findings have raised the possibility that salt-sensitive cardiovascular diseases could result, at least in part, from direct osmosensory activation of CNS sympathetic drive. In this brief review we emphasize recent findings from several laboratories, including our own, which demonstrate that neurons of the forebrain organum vasculosum laminae terminalis (OVLT) play a pivotal role in triggering hyperosmotic activation of SNA by recruiting neurons in specific regions of the hypothalamus, brainstem and spinal cord. Although OVLT neurons are intrinsically osmosensitive and shrink when exposed to extracellular hypertonicity, it is not yet clear if these processes are functionally linked. Whereas acute hypertonic activation of OVLT neurons critically depends on TRPV1 channels, studies in TRPV1−/− mice suggest that acute and long-term osmoregulatory responses remain largely intact. Therefore, acute and chronic osmosensory transduction by OVLT neurons may be mediated by distinct mechanisms. We speculate that organic osmolytes such as taurine and possibly novel processes such as extracellular acidification could contribute to long-term osmosensory transduction by OVLT neurons and might therefore participate in the elevation of SNA in salt-sensitive cardiovascular diseases. PMID:20603334

  4. Synaptic activity and Alzheimer's disease: a critical update

    PubMed Central

    Tampellini, Davide

    2015-01-01

    Synapses have been known for many years to be the crucial target of pathology in different forms of dementia, in particular Alzheimer's disease (AD). Synapses and their appropriate activation or inhibition are fundamental for the proper brain function. Alterations in synaptic/neuronal activity and brain metabolism are considered among the earliest symptoms linked to the progression of AD, and lead to a central question in AD research: what is the role played by synaptic activity in AD pathogenesis? Intriguingly, in the last decade, important studies demonstrated that the state of activation of synapses affects the homeostasis of beta-amyloid (Aβ) and tau, both of which aggregate and accumulate during AD, and are involved in neuronal dysfunction. In this review we aim to summarize the up-to-date data linking synaptic/neuronal activity with Aβ and tau; moreover, we also intend to provide a critical overview on brain activity alterations in AD, and their role in the disease's pathophysiology. PMID:26582973

  5. Impaired suppressor activity in children affected by coeliac disease.

    PubMed Central

    Pignata, C; Troncone, R; Monaco, G; Ciriaco, M; Farris, E; Carminati, G; Auricchio, S

    1985-01-01

    Immunoregulatory cells were enumerated in 19 coeliac disease children on a gluten free diet by means of monoclonal antibodies that define total T lymphocytes (T3), helper/inducer T cells (T4), suppressor/cytotoxic T cells (T8) and monocytes (M1), as well as by means of surface receptors for Fc fragments of IgM and IgG (T mu and T gamma, respectively). In addition, suppressor cell function was assessed in 17 coeliac disease patients by examining the ability of concanavalin-A (Con-A)-activated suppressor cells to inhibit autologous cell response to mitogenic stimulus as compared with age-matched controls. No statistically significant differences were found in the percentages of subsets defined by monoclonal antibodies between coeliac disease patients and age-matched controls, whereas coeliac disease patients had a significant decrease of the subpopulation bearing membrane receptor for Fc fragment of IgG. Mean value was 8.5% in coeliac patients versus 13.4% in age-matched controls. In the functional assay, mononuclear cells from 10 out of 17 coeliac disease patients either totally or partially failed to suppress responder cells after Con-A-activation. This defect is not related to HLA-DR status, because no difference was found between patients-HLA-matched and unmatched normal individuals. In this assay, mononuclear cells of three coeliac disease patients with low suppressor activity were able to inhibit responder cells to the same extent as controls, when indomethacin was used to block prostaglandin production in the induction phase of Con-A-activated suppressor cells. Our results suggest that an abnormality in immunoregulation may play a role in the pathogenesis of coeliac disease. PMID:3156076

  6. Cardiovascular symptoms in patients with systemic mast cell activation disease.

    PubMed

    Kolck, Ulrich W; Haenisch, Britta; Molderings, Gerhard J

    2016-08-01

    Traditionally, mast cell activation disease (MCAD) has been considered as just one rare (neoplastic) disease, mastocytosis, focused on the mast cell (MC) mediators tryptase and histamine and the suggestive, blatant symptoms of flushing and anaphylaxis. Recently another form of MCAD, the MC activation syndrome, has been recognized featuring inappropriate MC activation with little to no neoplasia and likely much more heterogeneously clonal and far more prevalent than mastocytosis. Increasing expertise and appreciation has been established for the truly very large menagerie of MC mediators and their complex patterns of release, engendering complex, nebulous presentations of chronic and acute illness best characterized as multisystem polymorbidity of generally inflammatory ± allergic theme. We describe the pathogenesis of MCAD with a particular focus on clinical cardiovascular symptoms and the therapeutic options for MC mediator-induced cardiovascular symptoms.

  7. Veterinary public health activities at FAO: echinococcosis/hydatid disease.

    PubMed

    Eddi, C; de Balogh, K; Lubroth, J; Amanfu, W; Speedy, A; Battaglia, D

    2004-12-01

    Cystic hydatidosis is a zoonotic disease that remain as a significant cause of human morbidity and mortality in many parts of the world. The disease has veterinary public health implications. FAO is involved with some activities in the control of echinococcosis/hydatid disease: within the Animal Production and Health Division the Veterinary Public Health (VHP) Programme is constituted by members of the different Services (Animal Health, Animal Production, and Livestock Policy) within the Division. FAO regular programme has also established a global network of professionals directly involved in VPH. Furthermore FAO's Technical Cooperation Projects (TCP) is a tool to assist member countries in responding to urgent and unforeseen demands.

  8. Functional activation of lymphocyte CD44 in peripheral blood is a marker of autoimmune disease activity.

    PubMed Central

    Estess, P; DeGrendele, H C; Pascual, V; Siegelman, M H

    1998-01-01

    Interactions between complementary receptors on leukocytes and endothelial cells play a central role in regulating extravasation from the blood and thereby affect both normal and pathologic inflammatory responses. CD44 on lymphocytes that has been "activated" to bind its principal ligand hyaluronate (HA) on endothelium can mediate the primary adhesion (rolling) of lymphocytes to vascular endothelial cells under conditions of physiologic shear stress, and this interaction is used for activated T cell extravasation into an inflamed site in vivo in mice (DeGrendele, H.C., P. Estess, L.J. Picker, and M.H. Siegelman. 1996. J. Exp. Med. 183:1119-1130. DeGrendele, H.D., P. Estess, and M.H. Siegelman. 1997. Science. 278:672-675. DeGrendele, H.C., P. Estess, and M.H. Siegelman. 1997. J. Immunol. 159: 2549-2553). Here, we have investigated the role of lymphocyte-borne-activated CD44 in the human and show that CD44-dependent primary adhesion is induced in human peripheral blood T cells through T cell receptor triggering. In addition, lymphocytes capable of CD44/HA-dependent rolling interactions can be found resident within inflamed tonsils. In analysis of peripheral bloods of patients from a pediatric rheumatology clinic, examining systemic lupus erythematosus, and a group of chronic arthropathies, expression of CD44-dependent primary adhesion strongly correlates with concurrent symptomatic disease, with 85% of samples from clinically active patients showing elevated levels of rolling activity (compared with only 4% of inactive patients). These rolling interactions are predominantly mediated by T cells. The results suggest that circulating T lymphocytes bearing activated CD44 are elevated under conditions of chronic inflammation and that these may represent a pathogenically important subpopulation of activated circulating cells that may provide a reliable marker for autoimmune or chronic inflammatory disease activity. PMID:9739051

  9. Diversity and Activity of Lysobacter Species from Disease Suppressive Soils

    PubMed Central

    Gómez Expósito, Ruth; Postma, Joeke; Raaijmakers, Jos M.; De Bruijn, Irene

    2015-01-01

    The genus Lysobacter includes several species that produce a range of extracellular enzymes and other metabolites with activity against bacteria, fungi, oomycetes, and nematodes. Lysobacter species were found to be more abundant in soil suppressive against the fungal root pathogen Rhizoctonia solani, but their actual role in disease suppression is still unclear. Here, the antifungal and plant growth-promoting activities of 18 Lysobacter strains, including 11 strains from Rhizoctonia-suppressive soils, were studied both in vitro and in vivo. Based on 16S rRNA sequencing, the Lysobacter strains from the Rhizoctonia-suppressive soil belonged to the four species Lysobacter antibioticus, Lysobacter capsici, Lysobacter enzymogenes, and Lysobacter gummosus. Most strains showed strong in vitro activity against R. solani and several other pathogens, including Pythium ultimum, Aspergillus niger, Fusarium oxysporum, and Xanthomonas campestris. When the Lysobacter strains were introduced into soil, however, no significant and consistent suppression of R. solani damping-off disease of sugar beet and cauliflower was observed. Subsequent bioassays further revealed that none of the Lysobacter strains was able to promote growth of sugar beet, cauliflower, onion, and Arabidopsis thaliana, either directly or via volatile compounds. The lack of in vivo activity is most likely attributed to poor colonization of the rhizosphere by the introduced Lysobacter strains. In conclusion, our results demonstrated that Lysobacter species have strong antagonistic activities against a range of pathogens, making them an important source for putative new enzymes and antimicrobial compounds. However, their potential role in R. solani disease suppressive soil could not be confirmed. In-depth omics'–based analyses will be needed to shed more light on the potential contribution of Lysobacter species to the collective activities of microbial consortia in disease suppressive soils. PMID:26635735

  10. Inflammation activation and resolution in human tendon disease

    PubMed Central

    Dakin, Stephanie G; Martinez, Fernando O; Yapp, Clarence; Wells, Graham; Oppermann, Udo; Dean, Benjamin JF; Smith, Richard DJ; Wheway, Kim; Watkins, Bridget; Roche, Lucy; Carr, Andrew J

    2016-01-01

    Improved understanding of the role of inflammation in tendon disease is required to facilitate therapeutic target discovery. We studied supraspinatus tendons from patients experiencing pain before and after surgical subacromial decompression treatment. Tendons were classified as having early, intermediate or advanced disease and inflammation was characterized through activation of pathways mediated by Interferon, NF-κB, glucocorticoid receptor and STAT-6. Inflammation signatures revealed expression of genes and proteins induced by Interferon and NF-κB in early stage disease and genes and proteins induced by STAT-6 and glucocorticoid receptor activation in advanced stage disease. The pro-resolving proteins FPR2/ALX and ChemR23 were increased in early stage disease compared to intermediate-advanced stage disease. Patients who were pain-free post-treatment had tendons with increased expression of CD206 and ALOX15 mRNA compared to tendons from patients who continued to experience pain post-treatment, suggesting that these genes and their pathways may moderate tendon pain. Stromal cells from diseased tendons cultured in vitro showed increased expression of NF-κB and Interferon target genes after treatment with lipopolysaccharide or IFNγ compared to stromal cells derived from healthy tendons. We identified 15-epi Lipoxin A4, a stable lipoxin metabolite derived from aspirin treatment, as potentially beneficial in the resolution of tendon inflammation. PMID:26511510

  11. [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.

  12. Nutrition and Physical Activity in Nonalcoholic Fatty Liver Disease

    PubMed Central

    Oliveira, Claudia P.; de Lima Sanches, Priscila; de Abreu-Silva, Erlon Oliveira; Marcadenti, Aline

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and it is associated with other medical conditions such as diabetes mellitus, metabolic syndrome, and obesity. The mechanisms of the underlying disease development and progression are not completely established and there is no consensus concerning the pharmacological treatment. In the gold standard treatment for NAFLD weight loss, dietary therapy, and physical activity are included. However, little scientific evidence is available on diet and/or physical activity and NAFLD specifically. Many dietary approaches such as Mediterranean and DASH diet are used for treatment of other cardiometabolic risk factors such as insulin resistance and type-2 diabetes mellitus (T2DM), but on the basis of its components their role in NAFLD has been discussed. In this review, the implications of current dietary and exercise approaches, including Brazilian and other guidelines, are discussed, with a focus on determining the optimal nonpharmacological treatment to prescribe for NAFLD. PMID:26770987

  13. Mental health status can reflect disease activity in rheumatoid arthritis

    PubMed Central

    Sokolovic, Sekib; Dervisevic, Vedina; Fisekovic, Saida

    2014-01-01

    Objective A significant number of patients with rheumatoid arthritis (RA) link the start of illness with psychological trauma or severe stress. Impaired mental health (IMH), defined as depression and anxiety with psychoneuroimmunological factors, can play a significant role in RA. The main objective of this research was to investigate the mutual correlation of IMH and RA activity, estimated by the laboratory and clinical parameters in RA patients. Material and Methods An open clinical prospective study that lasted for 6 months was designed. There were 72 patients included, 58 women and 14 men, aged 34 to 80 years and screened for mental health status. The study population was randomized following the Brief Symptoms Inventory (BSI) scale, comprised of 53 questions with a range from 0 (no symptoms) to 4 (severe). This mental test was done only once during the study. Following the results from the BSI scale, RA patients were divided into mentally stable and mentally unstable patients to investigate the influence of RA activity on mental health. The following laboratory and clinical parameters were analyzed: sex, age, erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), C-reactive protein (CRP), anti-cyclic citrullinated peptide (anti-CCP) antibody, and disease activity score (DAS28). All RA patients did not express extra-articular manifestations or Sjögren’s syndrome. The chi-square test, ANOVA, Pearson’s coefficient, and IBM Statistics - SPSS v19 were used. Results From a total of 72 RA patients, there were 44 mentally stable and 28 mentally unstable patients. All patients had either moderate or severe active disease. The only significant correlation of IMH and activity of RA was found in CRP and DAS28, but no significance was observed in ESR, RF, and anti-CCP. The DAS28 showed high disease activity with an average of 5.3 and CRP of 20.9 mg/L in patients with unstable mental health compared to stable mental health patients, where RA was associated with

  14. Sleep disorders and inflammatory disease activity: chicken or the egg?

    PubMed

    Parekh, Parth J; Oldfield Iv, Edward C; Challapallisri, Vaishnavi; Ware, J Catsby; Johnson, David A

    2015-04-01

    Sleep dysfunction is a highly prevalent condition that has long been implicated in accelerating disease states characterized by having an inflammatory component such as systemic lupus erythematosus, HIV, and multiple sclerosis. Inflammatory bowel disease (IBD) is a chronic, debilitating disease that is characterized by waxing and waning symptoms, which are a direct result of increased circulating inflammatory cytokines. Recent studies have demonstrated sleep dysfunction and the disruption of the circadian rhythm to result in an upregulation of inflammatory cytokines. Not only does this pose a potential trigger for disease flares but also an increased risk of malignancy in this subset of patients. This begs to question whether or not there is a therapeutic role of sleep cycle and circadian rhythm optimization in the prevention of IBD flares. Further research is needed to clarify the role of sleep dysfunction and alterations of the circadian rhythm in modifying disease activity and also in reducing the risk of malignancy in patients suffering from IBD.

  15. Inflammation, immune activation, and cardiovascular disease in HIV.

    PubMed

    Nou, Eric; Lo, Janet; Grinspoon, Steven K

    2016-06-19

    Cardiovascular disease is one of the leading causes of morbidity and mortality in people living with HIV. Several epidemiological studies have shown an increased risk of myocardial infarction and stroke compared to uninfected controls. Although traditional risk factors contribute to this increased risk of cardiovascular disease, HIV-specific mechanisms likely also play a role. Systemic inflammation has been linked to cardiovascular disease in several populations suffering from chronic inflammation, including people living with HIV. Although antiretroviral therapy reduces immune activation, levels of inflammatory markers remain elevated compared to uninfected controls. The causes of this sustained immune response are likely multifactorial and incompletely understood. In this review, we summarize the evidence describing the relationship between inflammation and cardiovascular disease and discuss potential anti-inflammatory treatment options for cardiometabolic disease in people living with HIV.

  16. [Physical activity in basic and primary prevention of cardiovascular disease].

    PubMed

    Sobieszczańska, Małgorzata; Kałka, Dariusz; Pilecki, Witold; Adamus, Jerzy

    2009-06-01

    On account of the frequency of appearing and character of atherosclerosis cardiac vascular disease, one of the most crucial elements of effective fight against it is preparation of complex preventive programs including as vast number of population as possible. Consequently, Benjamin and Smitch suggested attaching the notion of basic prevention to the standard division into primary and secondary one. The basic prevention, carrying out in the general population, should concern genetic predisposition, psychosocial factors, keeping up proper body weight, healthy eating and physical activity. Especially high hopes are connected with high efficiency, simplicity and low money-consumption of preventive activities associated with physical activity modification, which has a crucial influence on reducing negative impact of atherosclerosis hazard. The results of numerous scientific research, carried out in many countries and on various, large groups, proved undoubtedly that at the healthy adult people of both sex the systematic physical activity of moderate intensification plays an essential part in preventing CVD and decreasing the death risk because of that reason as well. Moreover, systematic physical exercises show many other health-oriented actions, thanks to which they have an influence on decreasing premature and total death rate. The risk of incidence of civilization-related diseases such as diabetes type II, hypertension, obesity, osteoporosis, tumors (of large intestine, breast, prostatic gland) and depression has decreased significantly. Unequivocally positive influence has been proved at many observations dedicated to health recreational physical activity and physical activity connected with professional work based on aerobe effort. The positive effects have been also observed at children population and senior population which is more and more numerous and the most at risk. The beneficial action of physical activity is connected with direct effect on organism

  17. Relationship between disease activity and infection in patients with spondyloarthropathies

    PubMed Central

    Martinez, A; Pacheco-Tena, C; Vazquez-Mellado, J; Burgos-Vargas, R

    2004-01-01

    Methods: A cross sectional study of 95 non-selected patients with SpA (62 men; mean age 26.4 years), who were examined for signs and symptoms of infection and their association with disease activity. 52 had ankylosing spondylitis (AS), 32 undifferentiated SpA (uSpA), 6 chronic reactive arthritis (ReA), and 5 psoriatic arthritis (PsA). Categorical data were analysed by χ2 or Fisher's tests. Results: 53 (56%) patients had infections: 41 (43%) upper respiratory tract (URT), 34 (36%) enteric, and 20 (21%) genitourinary infections. More infections occurred in HLA-B27 positive patients as a whole (39 v 5; p = 0.003) and in uSpA (12 v 2; p = 0.005). In AS and uSpA, infections occurred in ∼50%. 30/39 (77%) patients with active disease (group A) and 23/56 (41%) (group B) (p = 0.001) had infection. There were more enteric infections in group A (47%; p<0.001) and more URT infections in group B (52%; p = NS). 22/30 (73%) patients attributed disease activity to infection. Conclusion: Enteric, and less commonly, URT infections in Mexican patients with SpA, particularly those who were HLA-B27 positive, seem to have a role in the active phase of AS and uSpA. PMID:15361397

  18. Microglia-inhibiting activity of Parkinson's disease drug amantadine.

    PubMed

    Kim, Jong-Heon; Lee, Ho-Won; Hwang, Jaegyu; Kim, Jaehong; Lee, Min-Jeong; Han, Hyung-Soo; Lee, Won-Ha; Suk, Kyoungho

    2012-09-01

    Amantadine is currently used as an antiviral and an antiparkinsonian drug. Although the drug is known to bind a viral proton channel protein, the mechanism of action in Parkinson's disease (PD) remains to be determined. This study investigated whether the drug has an inhibitory effect on microglial activation and neuroinflammation, which have been implicated in the progression of neurodegenerative processes. Using cultured microglial cells, it was demonstrated that the drug inhibited inflammatory activation of microglia and a signaling pathway that governs the microglial activation. The drug reduced the expression and production of proinflammatory mediators in bacterial lipopolysaccharide-stimulated microglia cells. The microglia-inhibiting activity of amantadine was also demonstrated in a microglia/neuron coculture and animal models of neuroinflammation and Parkinson's disease. Collectively, our results suggest that amantadine may act on microglia in the central nervous system to inhibit their inflammatory activation, thereby attenuating neuroinflammation. These results provide a molecular basis of the glia-targeted mechanism of action for amantadine.

  19. Subthalamic nucleus neuronal activity in Parkinson's disease and epilepsy subjects.

    PubMed

    Montgomery, Erwin B

    2008-01-01

    Activity from 113 subthalamic nucleus (STN) neurons from two epilepsy patients and 103 neurons from 9 Parkinson's disease (PD) patients undergoing DBS surgery showed no significant differences in frequencies (PD, mean 7.5+/-7.0 spikes/s (sps), epilepsy mean 7.8+/-8.5 sps) or in the coefficients of variation of mean discharge frequencies per 1s epochs. A striking relationship between mean discharge frequencies per 1 s epochs and the standard deviations for both groups were consistent with a random Poisson processes. These and similar findings call into question theories that posit increased STN activity is causal to parkinsonism.

  20. Medicinal plant activity on Helicobacter pylori related diseases

    PubMed Central

    Wang, Yuan-Chuen

    2014-01-01

    More than 50% of the world population is infected with Helicobacter pylori (H. pylori). The bacterium highly links to peptic ulcer diseases and duodenal ulcer, which was classified as a group I carcinogen in 1994 by the WHO. The pathogenesis of H. pylori is contributed by its virulence factors including urease, flagella, vacuolating cytotoxin A (VacA), cytotoxin-associated gene antigen (Cag A), and others. Of those virulence factors, VacA and CagA play the key roles. Infection with H. pylori vacA-positive strains can lead to vacuolation and apoptosis, whereas infection with cagA-positive strains might result in severe gastric inflammation and gastric cancer. Numerous medicinal plants have been reported for their anti-H. pylori activity, and the relevant active compounds including polyphenols, flavonoids, quinones, coumarins, terpenoids, and alkaloids have been studied. The anti-H. pylori action mechanisms, including inhibition of enzymatic (urease, DNA gyrase, dihydrofolate reductase, N-acetyltransferase, and myeloperoxidase) and adhesive activities, high redox potential, and hydrophilic/hydrophobic natures of compounds, have also been discussed in detail. H. pylori-induced gastric inflammation may progress to superficial gastritis, atrophic gastritis, and finally gastric cancer. Many natural products have anti-H. pylori-induced inflammation activity and the relevant mechanisms include suppression of nuclear factor-κB and mitogen-activated protein kinase pathway activation and inhibition of oxidative stress. Anti-H. pylori induced gastric inflammatory effects of plant products, including quercetin, apigenin, carotenoids-rich algae, tea product, garlic extract, apple peel polyphenol, and finger-root extract, have been documented. In conclusion, many medicinal plant products possess anti-H. pylori activity as well as an anti-H. pylori-induced gastric inflammatory effect. Those plant products have showed great potential as pharmaceutical candidates for H. pylori

  1. Effect of 2 Psychotherapies on Depression and Disease Activity in Pediatric Crohn's Disease

    PubMed Central

    Youk, Ada O.; Gonzalez-Heydrich, Joseph; Bujoreanu, Simona I.; Weisz, John; Fairclough, Diane; Ducharme, Peter; Jones, Neil; Lotrich, Francis; Keljo, David; Srinath, Arvind; Bousvaros, Athos; Kupfer, David; DeMaso, David R.

    2015-01-01

    Background: Crohn's disease (CD) is associated with depression. It is unclear if psychosocial interventions offer benefit for depressive symptoms during active CD. In this secondary analysis of a larger study of treating depression in pediatric inflammatory bowel disease, we assessed whether cognitive behavioral therapy (CBT) would differentiate from supportive nondirective therapy in treating depression and disease activity in youth with CD. We also explored whether somatic depressive symptoms showed a different pattern of response in the overall sample and the subset with active inflammatory bowel disease. Methods: Youth with depression and CD (n = 161) were randomized to 3 months of CBT (teaching coping skills) or supportive nondirective therapy (supportive listening). Depressive severity was measured using the Children's Depression Rating Scale-Revised (CDRS-R) with the somatic depressive subtype consisting of those CDRS-R items, which significantly correlated with CD activity. Disease activity was measured by the Pediatric Crohn's disease Activity Index. Given the potential confound of higher dose steroids, subanalyses excluded subjects on >20 mg/d prednisone equivalent (n = 34). Results: Total CDRS-R scores in the overall sample significantly decreased over time after both treatments (P < 0.0001). Treatment with CBT was associated with a significantly greater improvement in the Pediatric Crohn's disease Activity Index (P = 0.05) and somatic depressive subtype (P = 0.03) in those with active inflammatory bowel disease (n = 95) compared with supportive nondirective therapy. After excluding those on steroids (n = 34), there was a significant improvement in total CDRS-R (P = 0.03) and in Pediatric Crohn's disease Activity Index (P = 0.03) after CBT. Conclusions: Psychotherapy may be a useful adjunct to treat depression in the context of CD-related inflammation in youth who are not concurrently on higher dose steroids. PMID:25822010

  2. IMMUNE ACTIVATION AND PAEDIATRIC HIV-1 DISEASE OUTCOME

    PubMed Central

    Roider, J; Muenchhoff, M; Goulder, PJR

    2016-01-01

    Purpose of review The paediatric HIV epidemic is changing. Over the past decade, new infections have substantially reduced whilst access to antiretroviral therapy (ART) has increased. Overall this success means that numbers of children living with HIV are climbing. In addition, the problems in adults of chronic inflammation resulting from persistent immune activation even following ART-mediated suppression of viral replication are magnified in children infected from birth. Recent findings Features of immune ontogeny favor low immune activation in early life, whilst specific aspects of paediatric HIV infection tend to increase it. A subset of ART-naïve non-progressing children exists in whom normal CD4 counts are maintained in the setting of persistent high viremia and yet in the context of low immune activation. This sooty mangabey-like phenotype contrasts with non-progressing adult infection characterized by the expression of protective HLA class I molecules and low viral load. The particular factors contributing to raised or lowered immune activation in paediatric infection, and that ultimately influence disease outcome, are discussed. Summary Novel strategies to circumvent the unwanted long-term consequences of HIV infection may be possible in children in whom natural immune ontogeny in early life militates against immune activation. Defining the mechanisms underlying low immune activation in natural HIV infection would have applications beyond paediatric HIV. PMID:26679413

  3. Endotoxin-like activity associated with Lyme disease Borrelia.

    PubMed

    Fumarola, D; Munno, I; Marcuccio, C; Miragliotta, G

    1986-12-01

    The newly recognized spirochete, Borrelia burgdorferi, the causative agent of Lyme Disease, has been examined for endotoxin-like activities as measured by the standard Farmacopea Ufficiale della Republica Italiana rabbit fever test and the Limulus amoebocyte lysate assay. The suspension of heat-killed microorganism caused a febrile response at a dose of 1 X 10(8) bacteria pro kilo. Similar results were obtained in the Limulus assay where the heat-killed spirochetes stimulated formation of solid clot until the concentration of 1 X 10(5) per ml. Both in pyrogen test and in Limulus assay heat-killed Escherichia coli exhibited a higher degree of potency. These results show that LD-Borrelia possess endotoxin-like activities which could help in understanding the pathogenesis of the clinical symptomatology of the disease.

  4. Neuropeptides and Microglial Activation in Inflammation, Pain, and Neurodegenerative Diseases

    PubMed Central

    2017-01-01

    Microglial cells are responsible for immune surveillance within the CNS. They respond to noxious stimuli by releasing inflammatory mediators and mounting an effective inflammatory response. This is followed by release of anti-inflammatory mediators and resolution of the inflammatory response. Alterations to this delicate process may lead to tissue damage, neuroinflammation, and neurodegeneration. Chronic pain, such as inflammatory or neuropathic pain, is accompanied by neuroimmune activation, and the role of glial cells in the initiation and maintenance of chronic pain has been the subject of increasing research over the last two decades. Neuropeptides are small amino acidic molecules with the ability to regulate neuronal activity and thereby affect various functions such as thermoregulation, reproductive behavior, food and water intake, and circadian rhythms. Neuropeptides can also affect inflammatory responses and pain sensitivity by modulating the activity of glial cells. The last decade has witnessed growing interest in the study of microglial activation and its modulation by neuropeptides in the hope of developing new therapeutics for treating neurodegenerative diseases and chronic pain. This review summarizes the current literature on the way in which several neuropeptides modulate microglial activity and response to tissue damage and how this modulation may affect pain sensitivity. PMID:28154473

  5. The fecal microbiota as a biomarker for disease activity in Crohn’s disease

    PubMed Central

    Tedjo, Danyta. I.; Smolinska, Agnieszka; Savelkoul, Paul H.; Masclee, Ad A.; van Schooten, Frederik J.; Pierik, Marieke J.; Penders, John; Jonkers, Daisy M. A. E.

    2016-01-01

    Monitoring mucosal inflammation is crucial to prevent complications and disease progression in Crohn’s disease (CD). Endoscopy is the current standard, but is invasive. Clinical activity scores and non-invasive biochemical markers do not correlate well with mucosal inflammation. Microbial perturbations have been associated with disease activity in CD. Therefore, we aimed to investigate its potential use to differentiate CD patients in remission from those with an exacerbation. From 71 CD patients repeated fecal samples were collected, resulting in 97 active disease and 97 remission samples based on a combination of biochemical and clinical parameters. The microbiota composition was assessed by pyrosequencing of the 16S rRNA V1-V3 region. Random Forest analysis was used to find the most discriminatory panel of operational taxonomic units (OTUs) between active and remission samples. An independent internal validation set was used to validate the model. A combination of 50 OTUs was able to correctly predict 73% of remission and 79% of active samples with an AUC of 0.82 (sensitivity: 0.79, specificity: 0.73). This study demonstrates that fecal microbial profiles can be used to differentiate between active and remission CD and underline the potential of the fecal microbiota as a non-invasive tool to monitor disease activity in CD. PMID:27734914

  6. [Physical activity in the prevention and treatment of cardiovascular diseases].

    PubMed

    Mirat, Jure

    2007-01-01

    Cardiovascular diseases represent the leading health problem of the modern age. They are the first cause of mortality in developed as well as in transition countries. Physical activity has a beneficial impact on the cardiovascular system, both directly by improving endothelial function and indirectly by normalizing risk factors of atherosclerosis, such as dyslipidemia, high blood pressure, obesity and by positive effects on coagulation mechanism. The impact of physical activity on the cardiovascular system is manifested by immediate changes in hemodynamics, blood pressure and heart rate during physical training. After some time, consequences of continuous training are manifested as a decrease in the basal heart rate, blood pressure and heart rate responsiveness to physical activity stress, which indicates good conditioning i.e. increased physical capacity. Prospective epidemiological studies have shown that sedentary style of life has a twice-higher risk of sudden death and cardiovascular mortality. Physical activity should be permanent to have positive effects on the cardiovascular system; it means 4 to 5 times weekly depending on duration and intensity of exercises. In case of exercises 60-75% of the maximum, duration should be 30 to 45 minutes. Evidence based data show a 20-25 % lower mortality rate after myocardial infarction in the patients submitted to rehabilitation program of physical exercises. Physical activity in patients with coronary artery disease must be individualized, quantified and under control. In subjects with impaired function of the heart muscle, physical activity is limited with characteristic symptoms - dyspnea and stenocardia. These patients are classified into groups with mild, moderate and high risk, and based on this the allowed intensity of their physical activity is assessed, as well as the grade of its control. Physical exercises must be without range of tolerance and must not exceed this limit of symptoms. The aim of physical

  7. NOX Activation by Subunit Interaction and Underlying Mechanisms in Disease

    PubMed Central

    Rastogi, Radhika; Geng, Xiaokun; Li, Fengwu; Ding, Yuchuan

    2017-01-01

    Nicotinamide adenine dinucleotide phosphate (NAPDH) oxidase (NOX) is an enzyme complex with the sole function of producing superoxide anion and reactive oxygen species (ROS) at the expense of NADPH. Vital to the immune system as well as cellular signaling, NOX is also involved in the pathologies of a wide variety of disease states. Particularly, it is an integral player in many neurological diseases, including stroke, TBI, and neurodegenerative diseases. Pathologically, NOX produces an excessive amount of ROS that exceed the body’s antioxidant ability to neutralize them, leading to oxidative stress and aberrant signaling. This prevalence makes it an attractive therapeutic target and as such, NOX inhibitors have been studied and developed to counter NOX’s deleterious effects. However, recent studies of NOX have created a better understanding of the NOX complex. Comprised of independent cytosolic subunits, p47-phox, p67-phox, p40-phox and Rac, and membrane subunits, gp91-phox and p22-phox, the NOX complex requires a unique activation process through subunit interaction. Of these subunits, p47-phox plays the most important role in activation, binding and translocating the cytosolic subunits to the membrane and anchoring to p22-phox to organize the complex for NOX activation and function. Moreover, these interactions, particularly that between p47-phox and p22-phox, are dependent on phosphorylation initiated by upstream processes involving protein kinase C (PKC). This review will look at these interactions between subunits and with PKC. It will focus on the interaction involving p47-phox with p22-phox, key in bringing the cytosolic subunits to the membrane. Furthermore, the implication of these interactions as a target for NOX inhibitors such as apocynin will be discussed as a potential avenue for further investigation, in order to develop more specific NOX inhibitors based on the inhibition of NOX assembly and activation. PMID:28119569

  8. Variations in human liver fucosyltransferase activities in hepatobiliary diseases.

    PubMed

    Jezequel-Cuer, M; Dalix, A M; Flejou, J F; Durand, G

    1992-06-01

    The hyperfucosylation of a number of glycoconjugates observed in liver diseases involves the action of several specific fucosyltransferases (F.T.) notably responsible for synthesizing histo-blood group antigens. We determined the activities of alpha 3, alpha 2 and alpha 3/4 F.T. in 35 liver biopsy samples from patients with fatty liver, alcoholic or post-hepatic liver cirrhosis, primary or secondary biliary cirrhosis, acute hepatitis or a normal liver. F.T. activities were measured by transfer of GDP [14C] fucose to asialotransferrin for alpha 3 F.T., to phenyl beta-D-galactoside for alpha 2 F.T. and to 2' fucosyllactose for alpha 3/4 F.T. The diseased liver extracts showed an early increase in non-Le gene-associated alpha 3 F.T. activity (p = 0.001), which was related to the number of steatosic hepatocytes and the degree of intralobular inflammatory infiltration. Overexpression of this alpha 3 F.T. provides an explanation for the strong expression of 3-fucosyl lactosamine structures described in several hepatobiliary diseases. alpha 2 F.T. levels were significantly elevated in the two groups of liver cirrhosis and acute hepatitis (p = 0.05), but not enough to consider alpha 2 F.T. as a sensitive feature of mesenchymal cell injury. All Lewis-positive biopsies displaying biliary alterations showed increased Le gene-encoded alpha 3/4 F.T. activity (p = 0.001), which was related to the intensity of neoductular proliferation. Elevated levels of alpha 3/4 F.T. may be a very early sign of biliary regeneration.

  9. Neuroinflammation and Alzheimer's Disease: Implications for Microglial Activation.

    PubMed

    Regen, Francesca; Hellmann-Regen, Julian; Costantini, Erica; Reale, Marcella

    2017-02-03

    Microglial activation is a hallmark of neuroinflammation, seen in most acute and chronic neuropsychiatric conditions. With growing knowledge about microglia functions in surveying the brain for alterations, microglial activation is increasingly discussed in the context of disease progression and pathogenesis of Alzheimer's disease (AD). Underlying molecular mechanisms, however, remain largely unclear. While proper microglial function is essentially required for its scavenging duties, local activation of the brain's innate immune cells also brings about many less advantageous changes, such as reactive oxygen species (ROS) production, secretion of proinflammatory cytokines or degradation of neuroprotective retinoids, and may thus unnecessarily put surrounding healthy neurons in danger. In view of this dilemma, it is little surprising that both, AD vaccination trials, but also immunosuppressive strategies have consistently failed in AD patients. Nevertheless, epidemiological evidence has suggested a protective effect for anti-inflammatory agents, supporting the hypothesis that key processes involved in the pathogenesis of AD may take place rather early in the time course of the disorder, likely long before memory impairment becomes clinically evident. Activation of microglia results in a severely altered microenvironment. This is not only caused by the plethora of secreted cytokines, chemokines or ROS, but may also involve increased turnover of neuroprotective endogenous substances such as retinoic acid (RA), as recently shown in vitro. We discuss findings linking microglial activation and AD and speculate that microglial malfunction, which brings about changes in local RA concentrations in vitro, may underlie AD pathogenesis and precede or facilitate the onset of AD. Thus, chronic, "innate neuroinflammation" may provide a valuable target for preventive and therapeutic strategies.

  10. Inflammatory bowel diseases activity in patients undergoing pelvic radiation therapy

    PubMed Central

    Seisen, Thomas; Klotz, Caroline; Mazeron, Renaud; Maroun, Pierre; Petit, Claire; Deutsch, Eric; Bossi, Alberto; Haie-Meder, Christine; Chargari, Cyrus; Blanchard, Pierre

    2017-01-01

    Background Few studies with contradictory results have been published on the safety of pelvic radiation therapy (RT) in patients with inflammatory bowel disease (IBD). Methods From 1989 to 2015, a single center retrospective analysis was performed including all IBD patients who received pelvic external beam radiation therapy (EBRT) or brachytherapy (BT) for a pelvic malignancy. Treatment characteristics, IBD activity and gastrointestinal (GI) toxicity were examined. Results Overall, 28 patients with Crohn’s disease (CD) (n=13) or ulcerative colitis (n=15) were included in the present study. Median follow-up time after irradiation was 5.9 years. Regarding IBD activity, only one and two patients experienced a severe episode within and after 6 months of follow-up, respectively. Grade 3/4 acute GI toxicity occurred in 3 (11%) patients, whereas one (3.6%) patient experienced late grade 3/4 GI toxicity. Only patients with rectal IBD location (P=0.016) or low body mass index (BMI) (P=0.012) experienced more severe IBD activity within or after 6 months following RT, respectively. Conclusions We report an acceptable tolerance of RT in IBD patients with pelvic malignancies. Specifically, a low risk of uncontrolled flare-up was observed. PMID:28280621

  11. Protease-activated receptors and prostaglandins in inflammatory lung disease

    PubMed Central

    Peters, Terence; Henry, Peter J

    2009-01-01

    Protease-activated receptors (PARs) are a novel family of G protein-coupled receptors. Signalling through PARs typically involves the cleavage of an extracellular region of the receptor by endogenous or exogenous proteases, which reveals a tethered ligand sequence capable of auto-activating the receptor. A considerable body of evidence has emerged over the past 20 years supporting a prominent role for PARs in a variety of human physiological and pathophysiological processes, and thus substantial attention has been directed towards developing drug-like molecules that activate or block PARs via non-proteolytic pathways. PARs are widely expressed within the respiratory tract, and their activation appears to exert significant modulatory influences on the level of bronchomotor tone, as well as on the inflammatory processes associated with a range of respiratory tract disorders. Nevertheless, there is debate as to whether the principal response to PAR activation is an augmentation or attenuation of airways inflammation. In this context, an important action of PAR activators may be to promote the generation and release of prostanoids, such as prostglandin E2, which have well-established anti-inflammatory effects in the lung. In this review, we primarily focus on the relationship between PARs, prostaglandins and inflammatory processes in the lung, and highlight their potential role in selected respiratory tract disorders, including pulmonary fibrosis, asthma and chronic obstructive pulmonary disease. This article is part of a themed issue on Mediators and Receptors in the Resolution of Inflammation. To view this issue visit http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009 PMID:19845685

  12. Interleukin-19 impairment in active Crohn's disease patients.

    PubMed

    Cantó, Elisabet; Garcia Planella, Esther; Zamora-Atenza, Carlos; Nieto, Juan Camilo; Gordillo, Jordi; Ortiz, Ma Angels; Metón, Isidoro; Serrano, Elena; Vegas, Esteban; García-Bosch, Orlando; Juárez, Cándido; Vidal, Sílvia

    2014-01-01

    The exact function of interleukin-19 (IL-19) on immune response is poorly understood. In mice, IL-19 up-regulates TNFα and IL-6 expression and its deficiency increases susceptibility to DSS-induced colitis. In humans, IL-19 favors a Th2 response and is elevated in several diseases. We here investigate the expression and effects of IL-19 on cells from active Crohn's disease (CD) patient. Twenty-three active CD patients and 20 healthy controls (HC) were included. mRNA and protein IL-19 levels were analyzed in monocytes. IL-19 effects were determined in vitro on the T cell phenotype and in the production of cytokines by immune cells. We observed that unstimulated and TLR-activated monocytes expressed significantly lower IL-19 mRNA in active CD patients than in HC (logFC = -1.97 unstimulated; -1.88 with Pam3CSK4; and -1.91 with FSL-1; p<0.001). These results were confirmed at protein level. Exogenous IL-19 had an anti-inflammatory effect on HC but not on CD patients. IL-19 decreased TNFα production in PBMC (850.7 ± 75.29 pg/ml vs 2626.0 ± 350 pg/ml; p<0.01) and increased CTLA4 expression (22.04 ± 1.55% vs 13.98 ± 2.05%; p<0.05) and IL-4 production (32.5 ± 8.9 pg/ml vs 13.5 ± 2.9 pg/ml; p<0.05) in T cells from HC. IL-10 regulated IL-19 production in both active CD patients and HC. We observed that three of the miRNAs that can modulate IL-19 mRNA expression, were up-regulated in monocytes from active CD patients. These results suggested that IL-19 had an anti-inflammatory role in this study. Defects in IL-19 expression and the lack of response to this cytokine could contribute to inflammatory mechanisms in active CD patients.

  13. Reductions in disease activity in the AMPLE trial: clinical response by baseline disease duration

    PubMed Central

    Schiff, Michael; Weinblatt, Michael E; Valente, Robert; Citera, Gustavo; Maldonado, Michael; Massarotti, Elena; Yazici, Yusuf; Fleischmann, Roy

    2016-01-01

    Objectives To evaluate clinical response by baseline disease duration using 2-year data from the AMPLE trial. Methods Patients were randomised to subcutaneous abatacept 125 mg weekly or adalimumab 40 mg bi-weekly, with background methotrexate. As part of a post hoc analysis, the achievement of validated definitions of remission (Clinical Disease Activity Index (CDAI) ≤2.8, Simplified Disease Activity Index (SDAI) ≤3.3, Routine Assessment of Patient Index Data 3 (RAPID3) ≤3.0, Boolean score ≤1), low disease activity (CDAI <10, SDAI <11, RAPID3 ≤6.0), Health Assessment Questionnaire-Disability Index response and American College of Rheumatology responses were evaluated by baseline disease duration (≤6 vs >6 months). Disease Activity Score 28 (C-reactive protein) <2.6 or ≤3.2 and radiographic non-progression in patients achieving remission were also evaluated. Results A total of 646 patients were randomised and treated (abatacept, n=318; adalimumab, n=328). In both treatment groups, comparable responses were achieved in patients with early rheumatoid arthritis (≤6 months) and in those with later disease (>6 months) across multiple clinical measures. Conclusions Abatacept or adalimumab with background methotrexate were associated with similar onset and sustainability of response over 2 years. Patients treated early or later in the disease course achieved comparable clinical responses. Trial registration number NCT00929864, Post-results. PMID:27110385

  14. Study on cholesteryl ester transfer activity in coronary heart disease.

    PubMed

    Fujinuma, Y; Tanaka, A; Maezawa, H

    1991-09-01

    The net cholesterol transfer activity from high density lipoprotein (HDL) to low density lipoprotein (LDL) was determined in the patients with coronary heart disease (CHD) to examine its effect on the pathogenesis of arteriosclerosis. Furthermore, in the CHD patients with high HDL cholesterolemia (more than 60 mg/dl), the HDL particle size was measured by high performance liquid chromatography. A significant cholesteryl ester transfer activity (P less than 0.02) was noted in the CHD patients with low HDL cholesterolemia (less than 60 mg/dl). The rate of cholesteryl ester transfer activity (cholesteryl ester transfer activity/hour) inversely correlated with the serum HDL cholesterol value (r = -0.483, P = 0.096) in the patients with CHD. These results suggest that an increase of CETA caused a low HDL cholesterol value in the CHD patients with low HDL cholesterolemia and it may have the risk of causing CHD. However, an increase of the CETA was not found in the CHD patients with high HDL cholesterolemia compared to the normal subjects, the HDL particle size being significantly greater than that in the normal subjects. In the CHD patients with high HDL cholesterolemia, the large size of HDL may have the risk of causing CHD.

  15. 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

  16. Activating transcription factor 6 derepression mediates neuroprotection in Huntington disease.

    PubMed

    Naranjo, José R; Zhang, Hongyu; Villar, Diego; González, Paz; Dopazo, Xose M; Morón-Oset, Javier; Higueras, Elena; Oliveros, Juan C; Arrabal, María D; Prieto, Angela; Cercós, Pilar; González, Teresa; De la Cruz, Alicia; Casado-Vela, Juan; Rábano, Alberto; Valenzuela, Carmen; Gutierrez-Rodriguez, Marta; Li, Jia-Yi; Mellström, Britt

    2016-02-01

    Deregulated protein and Ca2+ homeostasis underlie synaptic dysfunction and neurodegeneration in Huntington disease (HD); however, the factors that disrupt homeostasis are not fully understood. Here, we determined that expression of downstream regulatory element antagonist modulator (DREAM), a multifunctional Ca2+-binding protein, is reduced in murine in vivo and in vitro HD models and in HD patients. DREAM downregulation was observed early after birth and was associated with endogenous neuroprotection. In the R6/2 mouse HD model, induced DREAM haplodeficiency or blockade of DREAM activity by chronic administration of the drug repaglinide delayed onset of motor dysfunction, reduced striatal atrophy, and prolonged life span. DREAM-related neuroprotection was linked to an interaction between DREAM and the unfolded protein response (UPR) sensor activating transcription factor 6 (ATF6). Repaglinide blocked this interaction and enhanced ATF6 processing and nuclear accumulation of transcriptionally active ATF6, improving prosurvival UPR function in striatal neurons. Together, our results identify a role for DREAM silencing in the activation of ATF6 signaling, which promotes early neuroprotection in HD.

  17. Activating transcription factor 6 derepression mediates neuroprotection in Huntington disease

    PubMed Central

    Naranjo, José R.; Zhang, Hongyu; Villar, Diego; González, Paz; Dopazo, Xose M.; Morón-Oset, Javier; Higueras, Elena; Oliveros, Juan C.; Arrabal, María D.; Prieto, Angela; Cercós, Pilar; González, Teresa; De la Cruz, Alicia; Casado-Vela, Juan; Rábano, Alberto; Valenzuela, Carmen; Gutierrez-Rodriguez, Marta; Li, Jia-Yi; Mellström, Britt

    2016-01-01

    Deregulated protein and Ca2+ homeostasis underlie synaptic dysfunction and neurodegeneration in Huntington disease (HD); however, the factors that disrupt homeostasis are not fully understood. Here, we determined that expression of downstream regulatory element antagonist modulator (DREAM), a multifunctional Ca2+-binding protein, is reduced in murine in vivo and in vitro HD models and in HD patients. DREAM downregulation was observed early after birth and was associated with endogenous neuroprotection. In the R6/2 mouse HD model, induced DREAM haplodeficiency or blockade of DREAM activity by chronic administration of the drug repaglinide delayed onset of motor dysfunction, reduced striatal atrophy, and prolonged life span. DREAM-related neuroprotection was linked to an interaction between DREAM and the unfolded protein response (UPR) sensor activating transcription factor 6 (ATF6). Repaglinide blocked this interaction and enhanced ATF6 processing and nuclear accumulation of transcriptionally active ATF6, improving prosurvival UPR function in striatal neurons. Together, our results identify a role for DREAM silencing in the activation of ATF6 signaling, which promotes early neuroprotection in HD. PMID:26752648

  18. 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

  19. Subcortical evoked activity and motor enhancement in Parkinson's disease.

    PubMed

    Anzak, Anam; Tan, Huiling; Pogosyan, Alek; Khan, Sadaquate; Javed, Shazia; Gill, Steven S; Ashkan, Keyoumars; Akram, Harith; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Green, Alexander L; Aziz, Tipu; Brown, Peter

    2016-03-01

    Enhancements in motor performance have been demonstrated in response to intense stimuli both in healthy subjects and in the form of 'paradoxical kinesis' in patients with Parkinson's disease. Here we identify a mid-latency evoked potential in local field potential recordings from the region of the subthalamic nucleus, which scales in amplitude with both the intensity of the stimulus delivered and corresponding enhancements in biomechanical measures of maximal handgrips, independent of the dopaminergic state of our subjects with Parkinson's disease. Recordings of a similar evoked potential in the related pedunculopontine nucleus - a key component of the reticular activating system - provide support for this neural signature in the subthalmic nucleus being a novel correlate of ascending arousal, propagated from the reticular activating system to exert an 'energizing' influence on motor circuitry. Future manipulation of this system linking arousal and motor performance may provide a novel approach for the non-dopaminergic enhancement of motor performance in patients with hypokinetic disorders such as Parkinson's disease.

  20. Subcortical evoked activity and motor enhancement in Parkinson's disease

    PubMed Central

    Anzak, Anam; Tan, Huiling; Pogosyan, Alek; Khan, Sadaquate; Javed, Shazia; Gill, Steven S.; Ashkan, Keyoumars; Akram, Harith; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Green, Alexander L.; Aziz, Tipu; Brown, Peter

    2016-01-01

    Enhancements in motor performance have been demonstrated in response to intense stimuli both in healthy subjects and in the form of ‘paradoxical kinesis’ in patients with Parkinson's disease. Here we identify a mid-latency evoked potential in local field potential recordings from the region of the subthalamic nucleus, which scales in amplitude with both the intensity of the stimulus delivered and corresponding enhancements in biomechanical measures of maximal handgrips, independent of the dopaminergic state of our subjects with Parkinson's disease. Recordings of a similar evoked potential in the related pedunculopontine nucleus – a key component of the reticular activating system – provide support for this neural signature in the subthalmic nucleus being a novel correlate of ascending arousal, propagated from the reticular activating system to exert an ‘energizing’ influence on motor circuitry. Future manipulation of this system linking arousal and motor performance may provide a novel approach for the non-dopaminergic enhancement of motor performance in patients with hypokinetic disorders such as Parkinson's disease. PMID:26687971

  1. Impaired Brain Creatine Kinase Activity in Huntington's Disease

    PubMed Central

    Zhang, S.F.; Hennessey, T.; Yang, L.; Starkova, N.N.; Beal, M.F.; Starkov, A.A.

    2011-01-01

    Background Huntington's disease (HD) is associated with impaired energy metabolism in the brain. Creatine kinase (CK) catalyzes ATP-dependent phosphorylation of creatine (Cr) into phosphocreatine (PCr), thereby serving as readily available high-capacity spatial and temporal ATP buffering. Objective: Substantial evidence supports a specific role of the Cr/PCr system in neurodegenerative diseases. In the brain, the Cr/PCr ATP-buffering system is established by a concerted operation of the brain-specific cytosolic enzyme BB-CK and ubiquitous mitochondrial uMt-CK. It is not yet established whether the activity of these CK isoenzymes is impaired in HD. Methods We measured PCr, Cr, ATP and ADP in brain extracts of 3 mouse models of HD – R6/2 mice, N171-82Q and HdhQ111 mice – and the activity of CK in cytosolic and mitochondrial brain fractions from the same mice. Results The PCr was significantly increased in mouse HD brain extracts as compared to nontransgenic littermates. We also found an approximately 27% decrease in CK activity in both cytosolic and mitochondrial fractions of R6/2 and N171-82Q mice, and an approximately 25% decrease in the mitochondria from HdhQ111 mice. Moreover, uMt-CK and BB-CK activities were approximately 63% lower in HD human brain samples as compared to nondiseased controls. Conclusion Our findings lend strong support to the role of impaired energy metabolism in HD, and point out the potential importance of impairment of the CK-catalyzed ATP-buffering system in the etiology of HD. PMID:21124007

  2. Activity enhances dopaminergic long-duration response in Parkinson disease

    PubMed Central

    Auinger, Peggy; Fahn, Stanley; Oakes, David; Shoulson, Ira; Kieburtz, Karl; Rudolph, Alice; Marek, Kenneth; Seibyl, John; Lang, Anthony; Olanow, C. Warren; Tanner, Caroline; Schifitto, Giovanni; Zhao, Hongwei; Reyes, Lydia; Shinaman, Aileen; Comella, Cynthia L.; Goetz, Christopher; Blasucci, Lucia M.; Samanta, Johan; Stacy, Mark; Williamson, Kelli; Harrigan, Mary; Greene, Paul; Ford, Blair; Moskowitz, Carol; Truong, Daniel D.; Pathak, Mayank; Jankovic, Joseph; Ondo, William; Atassi, Farah; Hunter, Christine; Jacques, Carol; Friedman, Joseph H.; Lannon, Margaret; Russell, David S.; Jennings, Danna; Fussell, Barbara; Standaert, David; Schwarzschild, Michael A.; Growdon, John H.; Tennis, Marsha; Gauthier, Serge; Panisset, Michel; Hall, Jean; Gancher, Stephen; Hammerstad, John P.; Stone, Claudia; Alexander-Brown, Barbara; Factor, Stewart A.; Molho, Eric; Brown, Diane; Evans, Sharon; Clark, Jeffrey; Manyam, Bala; Simpson, Patricia; Wulbrecht, Brian; Whetteckey, Jacqueline; Martin, Wayne; Roberts, Ted; King, Pamela; Hauser, Robert; Zesiewicz, Theresa; Gauger, Lisa; Trugman, Joel; Wooten, G. Frederick; Rost-Ruffner, Elke; Perlmutter, Joel; Racette, Brad A.; Suchowersky, Oksana; Ranawaya, Ranjit; Wood, Susan; Pantella, Carol; Kurlan, Roger; Richard, Irene; Pearson, Nancy; Caviness, John N.; Adler, Charles; Lind, Marlene; Simuni, Tanya; Siderowf, Andrew; Colcher, Amy; Lloyd, Mary; Weiner, William; Shulman, Lisa; Koller, William; Lyons, Kelly; Feldman, Robert G.; Saint-Hilaire, Marie H.; Ellias, Samuel; Thomas, Cathi-Ann; Juncos, Jorge; Watts, Ray; Partlow, Anna; Tetrud, James; Togasaki, Daniel M.; Stewart, Tracy; Mark, Margery H.; Sage, Jacob I.; Caputo, Debbie; Gould, Harry; Rao, Jayaraman; McKendrick, Ann; Brin, Mitchell; Danisi, Fabio; Benabou, Reina; Hubble, Jean; Paulson, George W.; Reider, Carson; Birnbaum, Alex; Miyasaki, Janis; Johnston, Lisa; So, Julie; Pahwa, Rajesh; Dubinsky, Richard M.; Wszolek, Zbigniew; Uitti, Ryan; Turk, Margaret; Tuite, Paul; Rottenberg, David; Hansen, Joy; Ramos, Serrano; Waters, Cheryl; Lew, Mark; Welsh, Mickie; Kawai, Connie; O'Brien, Christopher; Kumar, Rajeev; Seeberger, Lauren; Judd, Deborah; Barclay, C. Lynn; Grimes, David A.; Sutherland, Laura; Dawson, Ted; Reich, Stephen; Dunlop, Rebecca; Albin, Roger; Frey, Kirk; Wernette, Kristine; Fahn, Stanley; Oakes, David; Shoulson, Ira; Kieburtz, Karl; Rudolph, Alice; Marek, Kenneth; Seibyl, John; Lang, Anthony; Olanow, C. Warren; Tanner, Caroline; Schifitto, Giovanni; Zhao, Hongwei; Reyes, Lydia; Shinaman, Aileen; Comella, Cynthia L.; Goetz, Christopher; Blasucci, Lucia M.; Samanta, Johan; Stacy, Mark; Williamson, Kelli; Harrigan, Mary; Greene, Paul; Ford, Blair; Moskowitz, Carol; Truong, Daniel D.; Pathak, Mayank; Jankovic, Joseph; Ondo, William; Atassi, Farah; Hunter, Christine; Jacques, Carol; Friedman, Joseph H.; Lannon, Margaret; Russell, David S.; Jennings, Danna; Fussell, Barbara; Standaert, David; Schwarzschild, Michael A.; Growdon, John H.; Tennis, Marsha; Gauthier, Serge; Panisset, Michel; Hall, Jean; Gancher, Stephen; Hammerstad, John P.; Stone, Claudia; Alexander-Brown, Barbara; Factor, Stewart A.; Molho, Eric; Brown, Diane; Evans, Sharon; Clark, Jeffrey; Manyam, Bala; Simpson, Patricia; Wulbrecht, Brian; Whetteckey, Jacqueline; Martin, Wayne; Roberts, Ted; King, Pamela; Hauser, Robert; Zesiewicz, Theresa; Gauger, Lisa; Trugman, Joel; Wooten, G. Frederick; Rost-Ruffner, Elke; Perlmutter, Joel; Racette, Brad A.; Suchowersky, Oksana; Ranawaya, Ranjit; Wood, Susan; Pantella, Carol; Kurlan, Roger; Richard, Irene; Pearson, Nancy; Caviness, John N.; Adler, Charles; Lind, Marlene; Simuni, Tanya; Siderowf, Andrew; Colcher, Amy; Lloyd, Mary; Weiner, William; Shulman, Lisa; Koller, William; Lyons, Kelly; Feldman, Robert G.; Saint-Hilaire, Marie H.; Ellias, Samuel; Thomas, Cathi-Ann; Juncos, Jorge; Watts, Ray; Partlow, Anna; Tetrud, James; Togasaki, Daniel M.; Stewart, Tracy; Mark, Margery H.; Sage, Jacob I.; Caputo, Debbie; Gould, Harry; Rao, Jayaraman; McKendrick, Ann; Brin, Mitchell; Danisi, Fabio; Benabou, Reina; Hubble, Jean; Paulson, George W.; Reider, Carson; Birnbaum, Alex; Miyasaki, Janis; Johnston, Lisa; So, Julie; Pahwa, Rajesh; Dubinsky, Richard M.; Wszolek, Zbigniew; Uitti, Ryan; Turk, Margaret; Tuite, Paul; Rottenberg, David; Hansen, Joy; Ramos, Serrano; Waters, Cheryl; Lew, Mark; Welsh, Mickie; Kawai, Connie; O'Brien, Christopher; Kumar, Rajeev; Seeberger, Lauren; Judd, Deborah; Barclay, C. Lynn; Grimes, David A.; Sutherland, Laura; Dawson, Ted; Reich, Stephen; Dunlop, Rebecca; Albin, Roger; Frey, Kirk; Wernette, Kristine; Mendis, Tilak

    2012-01-01

    Objective: We tested the hypothesis that dopamine-dependent motor learning mechanism underlies the long-duration response to levodopa in Parkinson disease (PD) based on our studies in a mouse model. By data-mining the motor task performance in dominant and nondominant hands of the subjects in a double-blind randomized trial of levodopa therapy, the effects of activity and dopamine therapy were examined. Methods: We data-mined the Earlier versus Later Levodopa Therapy in Parkinson's Disease (ELLDOPA) study published in 2005 and performed statistical analysis comparing the effects of levodopa and dominance of handedness over 42 weeks. Results: The mean change in finger-tapping counts from baseline before the initiation of therapy to predose at 9 weeks and 40 weeks increased more in the dominant compared to nondominant hand in levodopa-treated subjects in a dose-dependent fashion. There was no significant difference in dominant vs nondominant hands in the placebo group. The short-duration response assessed by the difference of postdose performance compared to predose performance at the same visit did not show any significant difference between dominant vs nondominant hands. Conclusions: Active use of the dominant hand and dopamine replacement therapy produces synergistic effect on long-lasting motor task performance during “off” medication state. Such effect was confined to dopamine-responsive symptoms and not seen in dopamine-resistant symptoms such as gait and balance. We propose that long-lasting motor learning facilitated by activity and dopamine is a form of disease modification that is often seen in trials of medications that have symptomatic effects. PMID:22459675

  3. 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

  4. Peroxisome proliferator-activated receptors, metabolic syndrome and cardiovascular disease

    PubMed Central

    Azhar, Salman

    2011-01-01

    Metabolic syndrome (MetS) is a constellation of risk factors including insulin resistance, central obesity, dyslipidemia and hypertension that markedly increase the risk of Type 2 diabetes (T2DM) and cardiovascular disease (CVD). The peroxisome proliferators-activated receptor (PPAR) isotypes, PPARα, PPARδ/β and PPARγ are ligand-activated nuclear transcription factors, which modulate the expression of an array of genes that play a central role in regulating glucose, lipid and cholesterol metabolism, where imbalance can lead to obesity, T2DM and CVD. They are also drug targets, and currently, PPARα (fibrates) and PPARγ (thiazolodinediones) agonists are in clinical use for treating dyslipidemia and T2DM, respectively. These metabolic characteristics of the PPARs, coupled with their involvement in metabolic diseases, mean extensive efforts are underway worldwide to develop new and efficacious PPAR-based therapies for the treatment of additional maladies associated with the MetS. This article presents an overview of the functional characteristics of three PPAR isotypes, discusses recent advances in our understanding of the diverse biological actions of PPARs, particularly in the vascular system, and summarizes the developmental status of new single, dual, pan (multiple) and partial PPAR agonists for the clinical management of key components of MetS, T2DM and CVD. It also summarizes the clinical outcomes from various clinical trials aimed at evaluating the atheroprotective actions of currently used fibrates and thiazolodinediones. PMID:20932114

  5. Parsing brain activity associated with acupuncture treatment in Parkinson's diseases.

    PubMed

    Chae, Younbyoung; Lee, Hyejung; Kim, Hackjin; Kim, Chang-Hwan; Chang, Dae-Il; Kim, Kyung-Mi; Park, Hi-Joon

    2009-09-15

    Acupuncture, a common treatment modality within complementary and alternative medicine, has been widely used for Parkinson's disease (PD). Using functional magnetic resonance imaging (fMRI), we explored the neural mechanisms underlying the effect of specific and genuine acupuncture treatment on the motor function in patients with PD. Three fMRI scans were performed in random order in a block design, one for verum acupuncture (VA) treatment, another one for a covert placebo (CP), and the third one for an overt placebo (OP) at the motor function implicated acupoint GB34 on the left foot of 10 patients with PD. We calculated the contrast that subtracts the blood-oxygen-level dependent (BOLD) response for the acupuncture effect (VA vs. CP) and the placebo effect (CP vs. OP). We found a significant improvement in the motor function of the affected hand after acupuncture treatment. The putamen and the primary motor cortex were activated when patients with PD received the acupuncture treatment (VA vs. CP) and these activations correlated with individual enhanced motor function. Expectation towards acupuncture modality (CP vs. OP) elicited activation over the anterior cingulate gyrus, the superior frontal gyrus, and the superior temporal gyrus. These findings suggest that acupuncture treatment might facilitate improvement in the motor functioning of patients with PD via the basal ganglia-thalamocortical circuit.

  6. Brain Na+, K+-ATPase Activity In Aging and Disease

    PubMed Central

    de Lores Arnaiz, Georgina Rodríguez; Ordieres, María Graciela López

    2014-01-01

    Na+/K+ pump or sodium- and potassium-activated adenosine 5’-triphosphatase (Na+, K+-ATPase), its enzymatic version, is a crucial protein responsible for the electrochemical gradient across the cell membranes. It is an ion transporter, which in addition to exchange cations, is the ligand for cardenolides. This enzyme regulates the entry of K+ with the exit of Na+ from cells, being the responsible for Na+/K+ equilibrium maintenance through neuronal membranes. This transport system couples the hydrolysis of one molecule of ATP to exchange three sodium ions for two potassium ions, thus maintaining the normal gradient of these cations in animal cells. Oxidative metabolism is very active in brain, where large amounts of chemical energy as ATP molecules are consumed, mostly required for the maintenance of the ionic gradients that underlie resting and action potentials which are involved in nerve impulse propagation, neurotransmitter release and cation homeostasis. Protein phosphorylation is a key process in biological regulation. At nervous system level, protein phosphorylation is the major molecular mechanism through which the function of neural proteins is modulted in response to extracellular signals, including the response to neurotransmitter stimuli. It is the major mechanism of neural plasticity, including memory processing. The phosphorylation of Na+, K+-ATPase catalytic subunit inhibits enzyme activity whereas the inhibition of protein kinase C restores the enzyme activity. The dephosphorylation of neuronal Na+, K+-ATPase is mediated by calcineurin, a serine / threonine phosphatase. The latter enzyme is involved in a wide range of cellular responses to Ca2+ mobilizing signals, in the regulation of neuronal excitability by controlling the activity of ion channels, in the release of neurotransmitters and hormones, as well as in synaptic plasticity and gene transcription. In the present article evidence showing Na+, K+-ATPase involvement in signaling pathways

  7. Immortalized Parkinson's disease lymphocytes have enhanced mitochondrial respiratory activity

    PubMed Central

    Annesley, Sarah J.; Lay, Sui T.; De Piazza, Shawn W.; Sanislav, Oana; Hammersley, Eleanor; Allan, Claire Y.; Francione, Lisa M.; Bui, Minh Q.; Chen, Zhi-Ping; Ngoei, Kevin R. W.; Tassone, Flora; Kemp, Bruce E.; Storey, Elsdon; Evans, Andrew; Loesch, Danuta Z.

    2016-01-01

    ABSTRACT In combination with studies of post-mortem Parkinson's disease (PD) brains, pharmacological and genetic models of PD have suggested that two fundamental interacting cellular processes are impaired – proteostasis and mitochondrial respiration. We have re-examined the role of mitochondrial dysfunction in lymphoblasts isolated from individuals with idiopathic PD and an age-matched control group. As previously reported for various PD cell types, the production of reactive oxygen species (ROS) by PD lymphoblasts was significantly elevated. However, this was not due to an impairment of mitochondrial respiration, as is often assumed. Instead, basal mitochondrial respiration and ATP synthesis are dramatically elevated in PD lymphoblasts. The mitochondrial mass, genome copy number and membrane potential were unaltered, but the expression of indicative respiratory complex proteins was also elevated. This explains the increased oxygen consumption rates by each of the respiratory complexes in experimentally uncoupled mitochondria of iPD cells. However, it was not attributable to increased activity of the stress- and energy-sensing protein kinase AMPK, a regulator of mitochondrial biogenesis and activity. The respiratory differences between iPD and control cells were sufficiently dramatic as to provide a potentially sensitive and reliable biomarker of the disease state, unaffected by disease duration (time since diagnosis) or clinical severity. Lymphoblasts from control and PD individuals thus occupy two distinct, quasi-stable steady states; a ‘normal’ and a ‘hyperactive’ state characterized by two different metabolic rates. The apparent stability of the ‘hyperactive’ state in patient-derived lymphoblasts in the face of patient ageing, ongoing disease and mounting disease severity suggests an early, permanent switch to an alternative metabolic steady state. With its associated, elevated ROS production, the ‘hyperactive’ state might not cause pathology

  8. 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

  9. Activation of the JAK/STAT pathway in Behcet's disease.

    PubMed

    Tulunay, A; Dozmorov, M G; Ture-Ozdemir, F; Yilmaz, V; Eksioglu-Demiralp, E; Alibaz-Oner, F; Ozen, G; Wren, J D; Saruhan-Direskeneli, G; Sawalha, A H; Direskeneli, H

    2015-03-01

    Th1/Th17-type T-cell responses are upregulated in Behcet's disease (BD). However, signaling pathways associated with this aberrant immune response are not clarified. Whole-genome microarray profiling was performed with human U133 (Plus 2.0) chips using messenger RNA of isolated CD14(+) monocytes and CD4(+) T cells from peripheral blood mononucleated cell (PBMC) in patients with BD (n = 9) and healthy controls (HCs) (n = 9). Flow cytometric analysis of unstimulated (US) and stimulated (phytohaemagglutinin) signal transducer and activator of transcription (STAT3) and pSTAT3 expressions of PBMCs were also analyzed (BD and HC, both n = 26). Janus family of kinase (JAK1) was observed to be upregulated in both CD14(+) monocytes (1.95-fold) and CD4(+) T lymphocytes (1.40-fold) of BD patients. Using canonical pathway enrichment analysis, JAK/STAT signaling was identified as activated in both CD14(+) monocytes (P = 9.55E-03) and in CD4(+) lymphocytes (P =8.13E-04) in BD. Interferon signaling was also prominent among upregulated genes in CD14(+) monocytes (P = 5.62E-05). Glucocorticoid receptor signaling and interleukin (IL-6) signaling were among the most enriched pathways in differentially expressed genes in CD14+ monocytes (P = 2.45E-09 and 1.00E-06, respectively). Basal US total STAT3 expression was significantly higher in BD (1.2 vs 3.45, P < 0.05). The JAK1/STAT3 signaling pathway is activated in BD, possibly through the activation of Th1/Th17-type cytokines such as IL-2, interferon (IFN-γ), IL-6, IL-17 and IL-23.

  10. [Helper or suppressor activity of T lymphocytes in patients with Berger's disease].

    PubMed

    Biagi, R; Beltrandi, E; Rossi, L; Cagnoli, L; Fiorentini, G P

    1983-09-30

    We have studied the immunological aspects in ten cases of Berger disease. Interaction between B and T lymphocytes were investigated to define help or suppressor activity 6 cases have demonstrated help activity, while suppressor activity was observed in two cases.

  11. Cortical cathepsin D activity and immunolocalization in Alzheimer disease, critical coronary artery disease, and aging.

    PubMed

    Haas, U; Sparks, D L

    1996-09-01

    The activity and immunocytochemical localization of cathepsin D in the frontal cortex were investigated in patients with Alzheimer disease (AD) and two groups of nondemented subjects; individuals with critical coronary artery disease (cCAD; > 75% stenosis) and non-heart disease controls (non-HD). The cathepsin D activity significantly increased with age in the non-HD population. No such age-related increase was observed in either AD or cCAD. Enzymatic activity was significantly increased in only the midaged, but not the older AD and cCAD subjects compared to controls. Immunocytochemical reactivity paralleled cathepsin D enzymatic activity. Frontal cortex neurons displayed an increased accumulation of cathepsin D immunoreactivity in aging (non-HD controls) with a further increase in cCAD, especially in the midaged group. Such immunoreactivity was markedly increased in AD. There was also an apparent age-related increase in the number of cathepsin D immunoreactive neurons in the non-HD population and a disease-related increase in only the mid-aged AD and cCAD subjects compared to controls. Senile plaques (SP) occurred in all AD patients, many cCAD, and a few of the oldest non-HD subjects, and they were immunoreactive to cathepsin D in each group. The data suggest a possible relationship between activation of cathepsin D and SP formation in AD, cCAD, and aging.

  12. Constitutive Activation of G Protein-Coupled Receptors and Diseases: Insights into Mechanisms of Activation and Therapeutics

    PubMed Central

    Tao, Ya-Xiong

    2008-01-01

    The existence of constitutive activity for G protein-coupled receptors (GPCRs) was first described in 1980s. In 1991, the first naturally occurring constitutively active mutations in GPCRs that cause diseases were reported in rhodopsin. Since then, numerous constitutively active mutations that cause human diseases were reported in several additional receptors. More recently, loss of constitutive activity was postulated to also cause diseases. Animal models expressing some of these mutants confirmed the roles of these mutations in the pathogenesis of the diseases. Detailed functional studies of these naturally occurring mutations, combined with homology modeling using rhodopsin crystal structure as the template, lead to important insights into the mechanism of activation in the absence of crystal structure of GPCRs in active state. Search for inverse agonists on these receptors will be critical for correcting the diseases cause by activating mutations in GPCRs. Theoretically, these inverse agonists are better therapeutics than neutral antagonists in treating genetic diseases caused by constitutively activating mutations in GPCRs. PMID:18768149

  13. Changes in spontaneous brain activity in early Parkinson's disease.

    PubMed

    Yang, Hong; Zhou, Xiaohong Joe; Zhang, Min-Ming; Zheng, Xu-Ning; Zhao, Yi-Lei; Wang, Jue

    2013-08-09

    Resting state brain activity can provide valuable insights into the pathophysiology of Parkinson's disease (PD). The purpose of the present study was (a) to investigate abnormal spontaneous neuronal activity in early PD patients using resting-state functional MRI (fMRI) with a regional homogeneity (ReHo) method and (b) to demonstrate the potential of using changes in abnormal spontaneous neuronal activity for monitoring the progression of PD during its early stages. Seventeen early PD patients were assessed with the Unified Parkinson's Disease Rating Scale (UPDRS), the Hoehn and Yahr disability scale and the Mini-mental State Examination (MMSE) were compared with seventeen gender- and age-matched healthy controls. All subjects underwent MRI scans using a 1.5T General Electric Signa Excite II scanner. The MRI scan protocol included whole-brain volumetric imaging using a 3D inversion recovery prepared (IR-Prep) fast spoiled gradient-echo pulse sequence and 2D multi-slice (22 axial slices covering the whole brain) resting-state fMRI using an echo planar imaging (EPI) sequence. Images were analyzed in SPM5 together with a ReHo algorithm using the in-house software program REST. A corrected threshold of p<0.05 was determined by AlphaSim and used in statistical analysis. Compared with the healthy controls, the early PD group showed significantly increased ReHo in a number of brain regions, including the left cerebellum, left parietal lobe, right middle temporal lobe, right sub-thalamic nucleus areas, right superior frontal gyrus, middle frontal gyrus (MFG), right inferior parietal lobe (IPL), right precuneus lobe, left MFG and left IPL. Additionally, significantly reduced ReHo was also observed in the early PD patients in the following brain regions: the left putamen, left inferior frontal gyrus, right hippocampus, right anterior cingulum, and bilateral lingual gyrus. Moreover, in PD patients, ReHo in the left putamen was negatively correlated with the UPDRS scores (r=-0

  14. Measuring disease activity in Crohn’s disease: what is currently available to the clinician

    PubMed Central

    D’Incà, Renata; Caccaro, Roberta

    2014-01-01

    Crohn’s disease (CD) is a chronic inflammatory bowel disease characterized by a relapsing-remitting clinical behavior and dominated by intestinal inflammation. Being a chronic disorder that with time develops into a disabling disease, it is important to monitor the severity of inflammation to assess the efficacy of medication, rule out complications, and prevent progression. This is particularly true now that the goals of treatment are mucosal healing and deep remission. Endoscopy has always been the gold standard for assessing mucosal activity in CD, but its use is limited by its invasiveness and its inability to examine the small intestine, proximal to the terminal ileum. Enteroscopy and the less invasive small bowel capsule endoscopy enable the small bowel to be thoroughly explored and scores are emerging for classifying small bowel disease activity. Cross-sectional imaging techniques (ultrasound, magnetic resonance, computed tomography) are emerging as valid tools for monitoring CD patients, assessing inflammatory activity in the mucosa and the transmucosal extent of the disease, and for excluding extra-intestinal complications. Neither endoscopy nor imaging are suitable for assessing patients frequently, however. Noninvasive markers such as C-reactive protein, and fecal biomarkers such as calprotectin and lactoferrin, are therefore useful to confirm the inflammatory burden of the disease and to identify patients requiring further investigations. PMID:24876789

  15. Measuring disease activity in Crohn's disease: what is currently available to the clinician.

    PubMed

    D'Incà, Renata; Caccaro, Roberta

    2014-01-01

    Crohn's disease (CD) is a chronic inflammatory bowel disease characterized by a relapsing-remitting clinical behavior and dominated by intestinal inflammation. Being a chronic disorder that with time develops into a disabling disease, it is important to monitor the severity of inflammation to assess the efficacy of medication, rule out complications, and prevent progression. This is particularly true now that the goals of treatment are mucosal healing and deep remission. Endoscopy has always been the gold standard for assessing mucosal activity in CD, but its use is limited by its invasiveness and its inability to examine the small intestine, proximal to the terminal ileum. Enteroscopy and the less invasive small bowel capsule endoscopy enable the small bowel to be thoroughly explored and scores are emerging for classifying small bowel disease activity. Cross-sectional imaging techniques (ultrasound, magnetic resonance, computed tomography) are emerging as valid tools for monitoring CD patients, assessing inflammatory activity in the mucosa and the transmucosal extent of the disease, and for excluding extra-intestinal complications. Neither endoscopy nor imaging are suitable for assessing patients frequently, however. Noninvasive markers such as C-reactive protein, and fecal biomarkers such as calprotectin and lactoferrin, are therefore useful to confirm the inflammatory burden of the disease and to identify patients requiring further investigations.

  16. Usefulness of Endoscopic Indices in Determination of Disease Activity in Patients with Crohn's Disease

    PubMed Central

    Kucharski, Marcin; Karczewski, Jacek; Mańkowska-Wierzbicka, Dorota; Karmelita-Katulska, Katarzyna; Kaczmarek, Elżbieta; Iwanik, Katarzyna; Rzymski, Piotr; Grzymisławski, Marian; Linke, Krzysztof; Dobrowolska, Agnieszka

    2016-01-01

    Background. Assessment of endoscopic activity of Crohn's disease (CD) is of growing importance both in clinical practice and in clinical trials. The study aimed to assess which of the endoscopic indices used for evaluation of mucosal changes correlates with the currently used clinical indices for determination of disease activity and with the results of histopathological examination. Study. A group of 71 patients with CD and 52 individuals without a diagnosis of GI tract disease as a control group were investigated, considering clinical and histological severity of the disease and the severity of inflammatory changes in the bowel. Evaluation was conducted with the use of clinical, endoscopic, and histopathological indices. Endoscopic indices were then correlated with different clinical and histopathological indices with the aim of finding the strongest correlations. Results and Conclusions. Correlation between the clinical disease activity and the severity of endoscopic lesions in CD was shown in this study to be poor. The results also indicate that the optimal endoscopic index used in the diagnostic stage and in the assessment of treatment effects in CD is Simple Endoscopic Score for Crohn's Disease (SES-CD). PMID:26997952

  17. Serum Inflammatory Mediators as Markers of Human Lyme Disease Activity

    PubMed Central

    Soloski, Mark J.; Crowder, Lauren A.; Lahey, Lauren J.; Wagner, Catriona A.

    2014-01-01

    Chemokines and cytokines are key signaling molecules that orchestrate the trafficking of immune cells, direct them to sites of tissue injury and inflammation and modulate their states of activation and effector cell function. We have measured, using a multiplex-based approach, the levels of 58 immune mediators and 7 acute phase markers in sera derived from of a cohort of patients diagnosed with acute Lyme disease and matched controls. This analysis identified a cytokine signature associated with the early stages of infection and allowed us to identify two subsets (mediator-high and mediator-low) of acute Lyme patients with distinct cytokine signatures that also differed significantly (p<0.0005) in symptom presentation. In particular, the T cell chemokines CXCL9 (MIG), CXCL10 (IP-10) and CCL19 (MIP3B) were coordinately increased in the mediator-high group and levels of these chemokines could be associated with seroconversion status and elevated liver function tests (p = 0.027 and p = 0.021 respectively). There was also upregulation of acute phase proteins including CRP and serum amyloid A. Consistent with the role of CXCL9/CXCL10 in attracting immune cells to the site of infection, CXCR3+ CD4 T cells are reduced in the blood of early acute Lyme disease (p = 0.01) and the decrease correlates with chemokine levels (p = 0.0375). The levels of CXCL9/10 did not relate to the size or number of skin lesions but elevated levels of serum CXCL9/CXCL10 were associated with elevated liver enzymes levels. Collectively these results indicate that the levels of serum chemokines and the levels of expression of their respective chemokine receptors on T cell subsets may prove to be informative biomarkers for Lyme disease and related to specific disease manifestations. PMID:24740099

  18. HIV disease progression: immune activation, microbes, and a leaky gut.

    PubMed

    Douek, Daniel

    2007-01-01

    Recent findings indicate that the majority of all CD4+ T lymphocytes are lost during acute HIV infection, with mucosal compartments being most severely affected. The frequency of infection is very high in gut CD4+ T cells, and depletion of these cells persists into the chronic phase of infection. Infection is associated with increased gut permeability, with microbial translocation being evidenced by increased circulating lipopolysaccharide (LPS) levels. Plasma LPS levels correlate with systemic immune activation, which drives chronic HIV infection. Antiretroviral therapy reduces plasma LPS, and greater CD4+ T cell reconstitution is associated with lower LPS levels. These findings have a number of implications for therapeutic strategies. This article summarizes a presentation on HIV disease progression made by Daniel Douek, MD, PhD, at an International AIDS Society-USA Continuing Medical Education course in San Francisco in May 2007. The original presentation is available as a Webcast at www.iasusa.org.

  19. Use of prediction markets to forecast infectious disease activity.

    PubMed

    Polgreen, Philip M; Nelson, Forrest D; Neumann, George R

    2007-01-15

    Prediction markets have accurately forecasted the outcomes of a wide range of future events, including sales of computer printers, elections, and the Federal Reserve's decisions about interest rates. We propose that prediction markets may be useful for tracking and forecasting emerging infectious diseases, such as severe acute respiratory syndrome and avian influenza, by aggregating expert opinion quickly, accurately, and inexpensively. Data from a pilot study in the state of Iowa suggest that these markets can accurately predict statewide seasonal influenza activity 2-4 weeks in advance by using clinical data volunteered from participating health care workers. Information revealed by prediction markets may help to inform treatment, prevention, and policy decisions. Also, these markets could help to refine existing surveillance systems.

  20. BAX channel activity mediates lysosomal disruption linked to Parkinson disease.

    PubMed

    Bové, Jordi; Martínez-Vicente, Marta; Dehay, Benjamin; Perier, Celine; Recasens, Ariadna; Bombrun, Agnes; Antonsson, Bruno; Vila, Miquel

    2014-05-01

    Lysosomal disruption is increasingly regarded as a major pathogenic event in Parkinson disease (PD). A reduced number of intraneuronal lysosomes, decreased levels of lysosomal-associated proteins and accumulation of undegraded autophagosomes (AP) are observed in PD-derived samples, including fibroblasts, induced pluripotent stem cell-derived dopaminergic neurons, and post-mortem brain tissue. Mechanistic studies in toxic and genetic rodent PD models attribute PD-related lysosomal breakdown to abnormal lysosomal membrane permeabilization (LMP). However, the molecular mechanisms underlying PD-linked LMP and subsequent lysosomal defects remain virtually unknown, thereby precluding their potential therapeutic targeting. Here we show that the pro-apoptotic protein BAX (BCL2-associated X protein), which permeabilizes mitochondrial membranes in PD models and is activated in PD patients, translocates and internalizes into lysosomal membranes early following treatment with the parkinsonian neurotoxin MPTP, both in vitro and in vivo, within a time-frame correlating with LMP, lysosomal disruption, and autophagosome accumulation and preceding mitochondrial permeabilization and dopaminergic neurodegeneration. Supporting a direct permeabilizing effect of BAX on lysosomal membranes, recombinant BAX is able to induce LMP in purified mouse brain lysosomes and the latter can be prevented by pharmacological blockade of BAX channel activity. Furthermore, pharmacological BAX channel inhibition is able to prevent LMP, restore lysosomal levels, reverse AP accumulation, and attenuate mitochondrial permeabilization and overall nigrostriatal degeneration caused by MPTP, both in vitro and in vivo. Overall, our results reveal that PD-linked lysosomal impairment relies on BAX-induced LMP, and point to small molecules able to block BAX channel activity as potentially beneficial to attenuate both lysosomal defects and neurodegeneration occurring in PD.

  1. Dendritic integration in pyramidal neurons during network activity and disease.

    PubMed

    Palmer, Lucy M

    2014-04-01

    Neurons have intricate dendritic morphologies which come in an array of shapes and sizes. Not only do they give neurons their unique appearance, but dendrites also endow neurons with the ability to receive and transform synaptic inputs. We now have a wealth of information about the functioning of dendrites which suggests that the integration of synaptic inputs is highly dependent on both dendritic properties and neuronal input patterns. It has been shown that dendrites can perform non-linear processing, actively transforming synaptic input into Na(+) spikes, Ca(2+) plateau spikes and NMDA spikes. These membrane non-linearities can have a large impact on the neuronal output and have been shown to be regulated by numerous factors including synaptic inhibition. Many neuropathological diseases involve changes in how dendrites receive and package synaptic input by altering dendritic spine characteristics, ion channel expression and the inhibitory control of dendrites. This review focuses on the role of dendrites in integrating and transforming input and what goes wrong in the case of neuropathological diseases.

  2. Ubiquitin, Proteasomes and Proteolytic Mechanisms Activated by Kidney Disease

    PubMed Central

    Rajan, Vik; Mitch, William E.

    2008-01-01

    Summary The ubiquitin-proteasome system (UPS) includes 3 enzymes that conjugate ubiquitin to intracellular proteins that are then recognized and degraded in the proteasome. The process participates in the regulation of cell metabolism. In the kidney, the UPS regulates the turnover of transporters and signaling proteins and its activity is down regulated in acidosis-induced proximal tubular cell hypertrophy. In chronic kidney disease (CKD), muscle wasting occurs because complications of CKD including acidosis, insulin resistance, inflammation, and increased angiotensin II levels stimulate the UPS to degrade muscle proteins. This response also includes caspase-3 and calpains which act to cleave muscle proteins to provide substrates for the UPS. For example, caspase-3 degrades actomyosin, leaving a 14kD fragment of actin in muscle. The 14 kD actin fragment is increased in muscle of patient with kidney disease, burn injury and surgery. In addition, acidosis, insulin resistance, inflammation and angiotensin II stimulate glucocorticoid production. Glucocorticoids are also required for the muscle wasting that occurs in CKD. Thus, the UPS is involved in regulating kidney function and participates in highly organized responses that degrade muscle protein in response to loss of kidney function. PMID:18723090

  3. From Lysosomal Storage Diseases to NKT Cell Activation and Back

    PubMed Central

    Pereira, Cátia S.; Ribeiro, Helena; Macedo, M. Fatima

    2017-01-01

    Lysosomal storage diseases (LSDs) are inherited metabolic disorders characterized by the accumulation of different types of substrates in the lysosome. With a multisystemic involvement, LSDs often present a very broad clinical spectrum. In many LSDs, alterations of the immune system were described. Special emphasis was given to Natural Killer T (NKT) cells, a population of lipid-specific T cells that is activated by lipid antigens bound to CD1d (cluster of differentiation 1 d) molecules at the surface of antigen-presenting cells. These cells have important functions in cancer, infection, and autoimmunity and were altered in a variety of LSDs’ mouse models. In some cases, the observed decrease was attributed to defects in either lipid antigen availability, trafficking, processing, or loading in CD1d. Here, we review the current knowledge about NKT cells in the context of LSDs, including the alterations detected, the proposed mechanisms to explain these defects, and the relevance of these findings for disease pathology. Furthermore, the effect of enzyme replacement therapy on NKT cells is also discussed. PMID:28245613

  4. Biophenols pharmacology against the amyloidogenic activity in Alzheimer's disease.

    PubMed

    Omar, Syed Haris

    2017-02-26

    Alzheimer's disease characterized by misfolding, aggregation, and accumulation of amyloid fibrils in an insoluble form in the brain, is often known as amyloidosis. The process of aggregation follows a mechanism of seeded polymerization. For decades, a great number of failures in Alzheimer's disease (AD) drug development, with both small molecules and immunotherapies failing to establish a drug/placebo difference or having an unacceptable toxicity have led to the therapeutic research interest towards a group of anti-amyloidogenic compounds originated from plants called biophenols. A number of in vitro and in vivo studies have demonstrated that the plant biophenols bind with amyloid beta (Aβ) toxic oligomers and reducing the fibril formation and toxicity. The exact mechanism of biophenols action against Aβ toxicity is unknown, while studies have suggested the amyloid-binding affinity of biophenols affecting Aβ on various levels, e.g. by direct inhibiting fibril formation or steering oligomer formation into unstructured, inhibiting Aβ aggregation, and promoting nontoxic pathways. Furthermore, biophenols involved in the inhibition of Aβ progression (e.g., oxidative stress and neuroinflammation) and effecting the amyloid precursor protein processing through the direct or indirect inhibition of β-secretase (BACE-1), γ-secretase and/or activation of α-secretase. This critical review account for the biophenols as magic bullet targeting against Aβ, and simulation the results on how biophenols interact with the Aβ monomers and oligomers, highly desirable knowledge for predicting new efficient nutraceutical drugs.

  5. Markers of endothelial cell activation and immune activation are increased in patients with severe leptospirosis and associated with disease severity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objectives: Previous studies concluded that haemorrhage is one of the most accurate prognostic factors of mortality in leptospirosis. Therefore, endothelial cell activation was investigated in relation to disease severity in severe leptospirosis. Methods: Prospective cohort study of severe leptospi...

  6. Occupational and recreational physical activity and Parkinson's disease in Denmark.

    PubMed

    Shih, I-Fan; Starhof, Charlotte; Lassen, Christina Funch; Hansen, Johnni; Liew, Zeyan; Ritz, Beate

    2017-03-20

    Objectives This study aimed to examine whether occupational and physical activity (PA) at different ages contribute to Parkinson's disease (PD) risk in a large population-based case-control study in Denmark. Methods We identified 1828 PD patients from the Danish National Hospital Register and recruited 1909 gender and year of birth matched controls from the Danish Central Population Register. Occupational and leisure-time PA were determined from a job exposure matrix based on occupational history and self-reported leisure-time information. Results No association was found for occupational PA alone in men, but higher leisure-time PA (≥5 hours/week of strenuous activities) in young adulthood (15-25 years) was associated with a lower PD risk (adjusted odds ratio (OR adj) 0.75, 95% confidence interval (95% CI) 0.62-0.90); men who engaged in high occupational and high leisure-time PA in young adulthood had the lowest PD risk (OR adj0.58, 95% CI 0.41-0.81). Among women, inverse associations were found for occupation PA before age 50 (highest vs lowest, OR adj0.75, 95% CI 0.55-1.06) and strenuous leisure-time PA after age 50 (OR adj0.65, 95% CI 0.87-0.99); no clear pattern was seen for leisure and occupational PA combined. Conclusions We observed gender-specific inverse associations between occupational and leisure-time PA and PD risk; however, we cannot preclude reverse causation especially in older ages since PD has a long prodromal stage that might lead to a reduction of PA years before motor symptom onset and PD diagnosis.

  7. Pridopidine activates neuroprotective pathways impaired in Huntington Disease

    PubMed Central

    Geva, Michal; Kusko, Rebecca; Soares, Holly; Fowler, Kevin D.; Birnberg, Tal; Barash, Steve; -Wagner, Avia Merenlender; Fine, Tania; Lysaght, Andrew; Weiner, Brian; Cha, Yoonjeong; Kolitz, Sarah; Towfic, Fadi; Orbach, Aric; Laufer, Ralph; Zeskind, Ben; Grossman, Iris; Hayden, Michael R.

    2016-01-01

    Pridopidine has demonstrated improvement in Huntington Disease (HD) motor symptoms as measured by secondary endpoints in clinical trials. Originally described as a dopamine stabilizer, this mechanism is insufficient to explain the clinical and preclinical effects of pridopidine. This study therefore explored pridopidine’s potential mechanisms of action. The effect of pridopidine versus sham treatment on genome-wide expression profiling in the rat striatum was analysed and compared to the pathological expression profile in Q175 knock-in (Q175 KI) vs Q25 WT mouse models. A broad, unbiased pathway analysis was conducted, followed by testing the enrichment of relevant pathways. Pridopidine upregulated the BDNF pathway (P = 1.73E-10), and its effect on BDNF secretion was sigma 1 receptor (S1R) dependent. Many of the same genes were independently found to be downregulated in Q175 KI mice compared to WT (5.2e-7 < P < 0.04). In addition, pridopidine treatment upregulated the glucocorticoid receptor (GR) response, D1R-associated genes and the AKT/PI3K pathway (P = 1E-10, P = 0.001, P = 0.004, respectively). Pridopidine upregulates expression of BDNF, D1R, GR and AKT/PI3K pathways, known to promote neuronal plasticity and survival, as well as reported to demonstrate therapeutic benefit in HD animal models. Activation of S1R, necessary for its effect on the BDNF pathway, represents a core component of the mode of action of pridopidine. Since the newly identified pathways are downregulated in neurodegenerative diseases, including HD, these findings suggest that pridopidine may exert neuroprotective effects beyond its role in alleviating some symptoms of HD. PMID:27466197

  8. 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.

  9. Activated Complement Factors as Disease Markers for Sepsis

    PubMed Central

    Charchaflieh, Jean; Rushbrook, Julie; Worah, Samrat; Zhang, Ming

    2015-01-01

    Sepsis is a leading cause of death in the United States and worldwide. Early recognition and effective management are essential for improved outcome. However, early recognition is impeded by lack of clinically utilized biomarkers. Complement factors play important roles in the mechanisms leading to sepsis and can potentially serve as early markers of sepsis and of sepsis severity and outcome. This review provides a synopsis of recent animal and clinical studies of the role of complement factors in sepsis development, together with their potential as disease markers. In addition, new results from our laboratory are presented regarding the involvement of the complement factor, mannose-binding lectin, in septic shock patients. Future clinical studies are needed to obtain the complete profiles of complement factors/their activated products during the course of sepsis development. We anticipate that the results of these studies will lead to a multipanel set of sepsis biomarkers which, along with currently used laboratory tests, will facilitate earlier diagnosis, timely treatment, and improved outcome. PMID:26420913

  10. Active ingredients of ginger as potential candidates in the prevention and treatment of diseases via modulation of biological activities.

    PubMed

    Rahmani, Arshad H; Shabrmi, Fahad M Al; Aly, Salah M

    2014-01-01

    The current mode of treatment based on synthetic drugs is expensive and also causes genetic and metabolic alterations. However, safe and sound mode of treatment is needed to control the diseases development and progression. In this regards, medicinal plant and its constituents play an important role in diseases management via modulation of biological activities. Ginger, the rhizome of the Zingiber officinale, has shown therapeutic role in the health management since ancient time and considered as potential chemopreventive agent. Numerous studies based on clinical trials and animal model has shown that ginger and its constituents shows significant role in the prevention of diseases via modulation of genetic and metabolic activities. In this review, we focused on the therapeutics effects of ginger and its constituents in the diseases management, and its impact on genetic and metabolic activities.

  11. Physical activity and mild cognitive impairment and Alzheimer's disease.

    PubMed

    Lautenschlager, Nicola T; Cox, Kay; Kurz, Alexander F

    2010-09-01

    Regular physical activity undoubtedly has many health benefits for all age groups. In the past decade, researchers and clinicians have begun to focus their attention on whether physical activity also can improve health outcomes of older adults who experience mild cognitive impairment (MCI) or dementia. This ongoing question is gaining relevance in light of the aging of the world population and with it the rise of age-related conditions, such as cognitive impairment. Not surprisingly, physical activity is among the potential protective lifestyle factors mentioned when strategies to delay or prevent dementia are discussed. The first large-scale multidomain intervention trials are under way to put this to the test. This review aims to give an overview of recent trials of physical activity in patients with MCI or dementia.

  12. Complement activity and pharmacological inhibition in cardiovascular disease

    PubMed Central

    Théroux, Pierre; Martel, Catherine

    2006-01-01

    While complement is the most important component of humoral autoimmunity, and inflammation plays a key role in atherosclerosis, relatively few studies have looked at complement implications in atherosclerosis and its complications. C-reactive protein is a marker of inflammation and is also involved in atherosclerosis; it activates complement and colocalizes with activated complement proteins within the infarcting myocardium and the active atherosclerotic plaques. As new agents capable of modulating complement activity are being developed, new targets for the management of atherosclerosis are emerging that are related to autoimmunity and inflammation. The present paper reviews the putative roles of the various complement activation pathways in the development of atherosclerosis, in ST segment elevation and non-ST segment elevation acute coronary syndromes, and in coronary artery bypass graft surgery. It also provides a perspective on new therapeutic interventions being developed to modulate complement activity. These interventions include the C1 esterase inhibitor, which may be consumed in some inflammatory states resulting in the loss of one of the mechanisms inhibiting activation of the classical and lectin pathways; TP10, a recombinant protein of the soluble complement receptor type 1 (sCR1) which inhibits the C3 and C5 convertases of the common pathway by binding C3b and C4b; a truncated version of the soluble complement receptor type 1 CRI lacking the C4b binding site which selectively inhibits the alternative pathway; and pexelizumab, a monoclonal antibody selectively blocking C5 to prevent the activation of the terminal pathway that is involved in excessive inflammation and autoimmune responses. PMID:16498508

  13. Lymphocyte activation gene 3 and coronary artery disease

    PubMed Central

    Golden, Diana; Kolmakova, Antonina; Sura, Sunitha; Vella, Anthony T.; Manichaikul, Ani; Wang, Xin-Qun; Bielinski, Suzette J.; Taylor, Kent D.; Chen, Yii-Der Ida; Rich, Stephen S.

    2016-01-01

    BACKGROUND: The lipoprotein scavenger receptor BI (SCARB1) rs10846744 noncoding variant is significantly associated with atherosclerotic disease independently of traditional cardiovascular risk factors. We identified a potentially novel connection between rs10846744, the immune checkpoint inhibitor lymphocyte activation gene 3 (LAG3), and atherosclerosis. METHODS: In vitro approaches included flow cytometry, lipid raft isolation, phosphosignaling, cytokine measurements, and overexpressing and silencing LAG3 protein. Fasting plasma LAG3 protein was measured in hyperalphalipoproteinemic (HALP) and Multi-Ethnic Study of Atherosclerosis (MESA) participants. RESULTS: In comparison with rs10846744 reference (GG homozygous) cells, LAG3 protein levels by flow cytometry (P < 0.001), in lipid rafts stimulated and unstimulated (P = 0.03), and phosphosignaling downstream of B cell receptor engagement of CD79A (P = 0.04), CD19 (P = 0.04), and LYN (P = 0.001) were lower in rs10846744 risk (CC homozygous) cells. Overexpressing LAG3 protein in risk cells and silencing LAG3 in reference cells confirmed its importance in phosphosignaling. Secretion of TNF-α was higher (P = 0.04) and IL-10 was lower (P = 0.04) in risk cells. Plasma LAG3 levels were lower in HALP carriers of the CC allele (P < 0.0001) and by race (P = 0.004). In MESA, race (P = 0.0005), age (P = 0.003), lipid medications (P = 0.03), smoking history (P < 0.0001), and rs10846744 genotype (P = 0.002) were independent predictors of plasma LAG3. In multivariable regression models, plasma LAG3 was significantly associated with HDL-cholesterol (HDL-C) (P = 0.007), plasma IL-10 (P < 0.0001), and provided additional predictive value above the Framingham risk score (P = 0.04). In MESA, when stratified by high HDL-C, plasma LAG3 was associated with coronary heart disease (CHD) (odds ratio 1.45, P = 0.004). CONCLUSION: Plasma LAG3 is a potentially novel independent predictor of HDL-C levels and CHD risk. FUNDING: This work was

  14. Lymphocyte activation gene 3 and coronary artery disease.

    PubMed

    Golden, Diana; Kolmakova, Antonina; Sura, Sunitha; Vella, Anthony T; Manichaikul, Ani; Wang, Xin-Qun; Bielinski, Suzette J; Taylor, Kent D; Chen, Yii-Der Ida; Rich, Stephen S; Rodriguez, Annabelle

    2016-10-20

    BACKGROUND: The lipoprotein scavenger receptor BI (SCARB1) rs10846744 noncoding variant is significantly associated with atherosclerotic disease independently of traditional cardiovascular risk factors. We identified a potentially novel connection between rs10846744, the immune checkpoint inhibitor lymphocyte activation gene 3 (LAG3), and atherosclerosis. METHODS: In vitro approaches included flow cytometry, lipid raft isolation, phosphosignaling, cytokine measurements, and overexpressing and silencing LAG3 protein. Fasting plasma LAG3 protein was measured in hyperalphalipoproteinemic (HALP) and Multi-Ethnic Study of Atherosclerosis (MESA) participants. RESULTS: In comparison with rs10846744 reference (GG homozygous) cells, LAG3 protein levels by flow cytometry (P < 0.001), in lipid rafts stimulated and unstimulated (P = 0.03), and phosphosignaling downstream of B cell receptor engagement of CD79A (P = 0.04), CD19 (P = 0.04), and LYN (P = 0.001) were lower in rs10846744 risk (CC homozygous) cells. Overexpressing LAG3 protein in risk cells and silencing LAG3 in reference cells confirmed its importance in phosphosignaling. Secretion of TNF-α was higher (P = 0.04) and IL-10 was lower (P = 0.04) in risk cells. Plasma LAG3 levels were lower in HALP carriers of the CC allele (P < 0.0001) and by race (P = 0.004). In MESA, race (P = 0.0005), age (P = 0.003), lipid medications (P = 0.03), smoking history (P < 0.0001), and rs10846744 genotype (P = 0.002) were independent predictors of plasma LAG3. In multivariable regression models, plasma LAG3 was significantly associated with HDL-cholesterol (HDL-C) (P = 0.007), plasma IL-10 (P < 0.0001), and provided additional predictive value above the Framingham risk score (P = 0.04). In MESA, when stratified by high HDL-C, plasma LAG3 was associated with coronary heart disease (CHD) (odds ratio 1.45, P = 0.004). CONCLUSION: Plasma LAG3 is a potentially novel independent predictor of HDL-C levels and CHD risk. FUNDING: This work was

  15. Biological activity of bee propolis in health and disease.

    PubMed

    Khalil, Mahmoud Lotfy

    2006-01-01

    Propolis is a natural product derived from plant resins collected by honeybees. It is used by bees as glue, a general-purpose sealer, and as draught-extruder for beehives. Propolis has been used in folk medicine for centuries. It is known that propolis possesses anti-microbial, antioxidative, anti-ulcer and anti-tumor activities. Therefore, propolis has attracted much attention in recent years as a useful or potential substance used in medicine and cosmetics products. Furthermore, it is now extensively used in foods and beverages with the claim that it can maintain or improve human health. The chemical composition of propolis is quite complicated. More than 300 compounds such as polyphenols, phenolic aldehydes, sequiterpene quinines, coumarins, amino acids, steroids and inorganic compounds have been identified in propolis samples. The contents depend on the collecting location, time and plant source. Consequently, biological activities of propolis gathered from different phytogeographical areas and time periods vary greatly. In this review, the activity of bee propolis will be presented with special emphasis on the antitumor activity.

  16. Metabolic activity of sodium, measured by neutron activation, in the hands of patients suffering from bone diseases: concise communication

    SciTech Connect

    Spinks, T.J.; Bewley, D.K.; Paolillo, M.; Vlotides, J.; Joplin, G.F.; Ranicar, A.S.O.

    1980-01-01

    Turnover of sodium in the human hand was studied by neutron activation. Patients suffering from various metabolic abnormalities affecting the skeleton, who were undergoing routine neutron activation for the measurement of calcium, were investigated along with a group of healthy volunteers. Neutron activation labels the sodium atoms simultaneously and with equal probability regardless of the turnover time of individual body compartments. The loss of sodium can be described either by a sum of two exponentials or by a single power function. Distinctions between patients and normal subjects were not apparent from the exponential model but were brought out by the power function. The exponent of time in the latter is a measure of clearance rate. The mean values of this parameter in (a) a group of patients suffering from acromegaly; (b) a group including Paget's disease, osteoporosis, Cushing's disease, and hyperparathyroidism; and (c) a group of healthy subjects, were found to be significantly different from each other.

  17. Nucleosomes and neutrophil activation in sickle cell disease painful crisis.

    PubMed

    Schimmel, Marein; Nur, Erfan; Biemond, Bart J; van Mierlo, Gerard J; Solati, Shabnam; Brandjes, Dees P; Otten, Hans-Martin; Schnog, John-John; Zeerleder, Sacha

    2013-11-01

    Activated polymorphonuclear neutrophils play an important role in the pathogenesis of vaso-occlusive painful sickle cell crisis. Upon activation, polymorphonuclear neutrophils can form neutrophil extracellular traps. Neutrophil extracellular traps consist of a meshwork of extracellular DNA, nucleosomes, histones and neutrophil proteases. Neutrophil extracellular traps have been demonstrated to be toxic to endothelial and parenchymal cells. This prospective cohort study was conducted to determine neutrophil extracellular trap formation in sickle cell patients during steady state and painful crisis. As a measure of neutrophil extracellular traps, plasma nucleosomes levels were determined and polymorphonuclear neutrophil activation was assessed measuring plasma levels of elastase-α1-antitrypsin complexes in 74 patients in steady state, 70 patients during painful crisis, and 24 race-matched controls using Enzyme Linked Immunosorbent Assay. Nucleosome levels in steady state sickle cell patients were significantly higher than levels in controls. During painful crisis levels of both nucleosomes and elastase-α1-antitrypsin complexes increased significantly. Levels of nucleosomes correlated significantly to elastase-α1-antitrypsin complex levels during painful crisis, (Sr = 0.654, P<0.001). This was seen in both HbSS/HbSβ(0)-thalassemia (Sr=0.55, P<0.001) and HbSC/HbSβ(+-)thalassemia patients (Sr=0.90, P<0.001) during painful crisis. Levels of nucleosomes showed a correlation with length of hospital stay and were highest in patients with acute chest syndrome. These data support the concept that neutrophil extracellular trap formation and neutrophil activation may play a role in the pathogenesis of painful sickle cell crisis and acute chest syndrome.

  18. Salivary Platelet Activating Factor Levels in Periodontal Disease

    DTIC Science & Technology

    1991-05-01

    multifarious and is activated through multiple mediators. The inflammatory process can be subdivided into acute and chronic inflammation. Stedman’s Medical...Just recently, inflammed human gingival tissues were analyzed and found to contain PAF (Noguchi, et al, 1989). Thus, multiple components of the...17.9% release of peroxidase, 20.6% release of P-glucuronidase, 22.4% release of alkaline phosphatase and 28.8% release of aryl sulfatase . At higher

  19. Ghrelin and adipokines as circulating markers of disease activity in patients with Takayasu arteritis

    PubMed Central

    2012-01-01

    Introduction The current markers of disease activity in Takayasu arteritis (TA) are insufficient for proper assessment. We investigated circulating levels of unacylated and acylated ghrelin, leptin and adiponectin and their relationships with disease activity in patients with TA. Methods This study included 31 patients with TA and 32 sex-, age- and body mass index-matched healthy controls. Disease activity was assessed in TA patients using various tools, including Kerr's criteria, disease extent index-Takayasu, physician's global assessment, radiological parameters, and laboratory markers. Plasma unacylated and acylated ghrelin, and serum leptin and adiponectin levels were measured using an enzyme-linked immunosorbent assay. Results Unacylated and acylated ghrelin levels were found to be significantly lower in TA patients than that in healthy controls. Patients with active disease had lower unacylated ghrelin levels than those with inactive disease and had lower acylated ghrelin levels than healthy controls. Ghrelin levels were negatively correlated with various parameters of disease activity. The leptin/ghrelin ratio was significantly higher in TA patients than controls. It was positively correlated with disease activity. There was a positive correlation between unacylated and acylated ghrelin and a negative correlation between leptin and ghrelin. There was no statistical difference in adiponectin levels between TA patients and controls. The radiological activity markers were positively correlated with other parameters of disease activity. Conclusions This study suggests that plasma unacylated and acylated ghrelin levels may be useful in monitoring disease activity and planning treatment strategies for patients with TA. The serum leptin level and leptin/ghrelin ratio may also be used to help assess the disease activity. PMID:23259466

  20. [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.

  1. The Peroxisome Proliferator Activated Receptor‐γ Pioglitazone Improves Vascular Function and Decreases Disease Activity in Patients With Rheumatoid Arthritis

    PubMed Central

    Marder, Wendy; Khalatbari, Shokoufeh; Myles, James D.; Hench, Rita; Lustig, Susan; Yalavarthi, Srilakshmi; Parameswaran, Aishwarya; Brook, Robert D.; Kaplan, Mariana J.

    2013-01-01

    Background Rheumatoid arthritis (RA) is associated with heightened mortality due to atherosclerotic cardiovascular disease (CVD). Inflammatory pathways in RA negatively affect vascular physiology and promote metabolic disturbances that contribute to CVD. We hypothesized that the peroxisome proliferator activated receptor‐γ (PPAR‐γ) pioglitazone could promote potent vasculoprotective and anti‐inflammatory effects in RA. Methods and Results One hundred forty‐three non‐diabetic adult RA patients (76.2% female, age 55.2±12.1 [mean±SD]) on stable RA standard of care treatment were enrolled in a randomized, double‐blind placebo controlled crossover trial of 45 mg daily pioglitazone versus placebo, with a 3‐month duration/arm and a 2‐month washout period. Pulse wave velocity of the aorta (PWV), brachial artery flow mediated dilatation (FMD), nitroglycerin mediated dilatation (NMD), microvascular endothelial function (reactive hyperemia index [RHI]), and circulating biomarkers of inflammation, insulin resistance, and atherosclerosis risk all were quantified. RA disease activity was assessed with the 28‐Joint Count Disease Activity Score (DAS‐28) C‐reactive protein (CRP) and the Short Form (36) Health Survey quality of life questionnaire. When added to standard of care RA treatment, pioglitazone significantly decreased pulse wave velocity (ie, aortic stiffness) (P=0.01), while FMD and RHI remained unchanged when compared to treatment with placebo. Further, pioglitazone significantly reduced RA disease activity (P=0.02) and CRP levels (P=0.001), while improving lipid profiles. The drug was well tolerated. Conclusions Addition of pioglitazone to RA standard of care significantly improves aortic elasticity and decreases inflammation and disease activity with minimal safety issues. The clinical implications of these findings remain to be established. Clinical Trial Registration URL: ClinicalTrials.gov Unique Identifier: NCT00554853. PMID:24252844

  2. Pivotal Role of Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 in Inflammatory Pulmonary Diseases

    PubMed Central

    Qian, Feng; Deng, Jing; Wang, Gang; Ye, Richard D.; Christman, John W.

    2016-01-01

    Mitogen-activated protein kinase (MAPK)-activated protein kinase (MK2) is exclusively regulated by p38 MAPK in vivo. Upon activation of p38 MAPK, MK2 binds with p38 MAPK, leading to phosphorylation of TTP, Hsp27, Akt and Cdc25 that are involved in regulation of various essential cellular functions. In this review, we discuss current knowledge about molecular mechanisms of MK2 in regulation of TNF-α production, NADPH oxidase activation, neutrophil migration, and DNA-damage-induced cell cycle arrest which are involved in the molecular pathogenesis of acute lung injury, pulmonary fibrosis, and non-small-cell lung cancer. Collectively current and emerging new information indicate that developing MK2 inhibitors and blocking MK2-mediated signal pathways is a potential therapeutic strategy for treatment of inflammatory and fibrotic lung diseases and lung cancer. PMID:26119506

  3. Physical activity in primary and secondary prevention of cardiovascular disease: Overview updated

    PubMed Central

    Alves, Alberto J; Viana, João L; Cavalcante, Suiane L; Oliveira, Nórton L; Duarte, José A; Mota, Jorge; Oliveira, José; Ribeiro, Fernando

    2016-01-01

    Although the observed progress in the cardiovascular disease treatment, the incidence of new and recurrent coronary artery disease remains elevated and constitutes the leading cause of death in the developed countries. Three-quarters of deaths due to cardiovascular diseases could be prevented with adequate changes in lifestyle, including increased daily physical activity. New evidence confirms that there is an inverse dose-response relationship between physical activity and cardiovascular disease and mortality risk. However, participation in moderate to vigorous physical activity may not fully attenuate the independent effect of sedentary activities on increased risk for cardiovascular diseases. Physical activity also plays an important role in secondary prevention of cardiovascular diseases by reducing the impact of the disease, slowing its progress and preventing recurrence. Nonetheless, most of eligible cardiovascular patients still do not benefit from secondary prevention/cardiac rehabilitation programs. The present review draws attention to the importance of physical activity in the primary and secondary prevention of cardiovascular diseases. It also addresses the mechanisms by which physical activity and regular exercise can improve cardiovascular health and reduce the burden of the disease. PMID:27847558

  4. The Disease Activity Score (DAS) and the Disease Activity Score using 28 joint counts (DAS28) in the management of rheumatoid arthritis.

    PubMed

    van Riel, Piet L C M; Renskers, Lisanne

    2016-01-01

    In rheumatoid arthritis (RA), disease activity cannot be measured in all individual patients according to a single variable. The Disease Activity Score (DAS) and the DAS28 have been developed to measure disease activity in RA both in daily clinical practice as well as in clinical trials on a group as well as individual level. The DAS/DAS28 is a continuous measure of RA disease activity that combines information from swollen joints, tender joints, acute phase response and general health. The DAS-based EULAR response criteria were primarily developed to be used in clinical trials. The EULAR response criteria classify individual patients as non-, moderate, or good responders, dependent on the magnitude of change and level of disease activity reached. In addition, already in the early nineties, cut points were developed to categorise patients in remission. The DAS28 is incorporated in several electronic patient records and web-based systems for monitoring purposes in daily clinical practice. In addition to this, it is being used in combination with patient-reported outcome measures (PROMs) to facilitate self-monitoring.

  5. Correlation of Cough With Disease Activity and Treatment With Cyclophosphamide in Scleroderma Interstitial Lung Disease

    PubMed Central

    Tseng, Chi-Hong; Li, Ning; Elashoff, Robert M.; Tashkin, Donald P.

    2012-01-01

    Background: Cough is a significant symptom in patients with scleroderma interstitial lung disease (SSc-ILD), affecting 73% of the 158 patients enrolled in the Scleroderma Lung Study (SLS), a multicenter randomized trial of oral cyclophosphamide (CYC) vs placebo (PLA) in patients with active interstitial lung disease. Methods: We examined the correlation of cough frequency and severity and phlegm production at baseline in 156 SLS participants with other baseline variables representing SSc-ILD disease activity and the cough response to 1 year of treatment with CYC vs PLA. Results: Patients with cough at baseline had significantly lower diffusing capacity of the lung for carbon monoxide, dyspnea, the quality-of-life physical component summary, and the maximal fibrosis score on high-resolution CT imaging compared with those without cough at baseline. Cough severity and frequency correlated with FVC % predicted. After 12 months of treatment, cough frequency decreased in the CYC group compared with the PLA group and was significantly different from the PLA group at 18 months (6 months after discontinuation of CYC). However, the decreases in cough frequency did not correlate with the changes in FVC or diffusing capacity of the lung for carbon monoxide observed in the CYC group. Treatment-related improvements in cough frequency, as well as in FVC, were no longer apparent 12 months after discontinuation of CYC. Conclusions: Cough is a common symptom in SSc-ILD and correlates with the extent of fibrosis. Cough frequency decreases significantly in response to treatment with CYC but returns to baseline 1 year after withdrawal of treatment. Cough may be a symptom of ongoing fibrosis and an independent variable in assessing therapeutic response to CYC. Trial registry: ClinicalTrials.gov; No.: NCT000004563; URL: www.clinicaltrials.gov PMID:22156609

  6. Serum Cytokine Profile in Asian Indian Patients with Takayasu Arteritis and its Association with Disease Activity

    PubMed Central

    Goel, Ruchika; Kabeerdoss, Jayakanthan; Ram, Babu; Prakash, John Antony Jude; Babji, Sudhir; Nair, Aswin; Jeyaseelan, Lakshmanan; Jeyaseelan, Visalakshi; Mathew, John; Balaji, Veeraraghavan; Joseph, George; Danda, Debashish

    2017-01-01

    Background: Arterial inflammation Takayasu arteritis (TA) is an outcome of balance between pro- and anti-inflammatory cytokines. Comprehensive assessment of these cytokines is important for understanding pathogenesis and assessing disease activity. Objective: To study pro- and anti-inflammatory cytokines representing different T-helper cell pathway in serum samples of Asian Indian patients with TA and to assess their association with disease activity. Methods: Consecutive Indian patients with TA were assayed for serum interferon-γ, interleukin-6, interleukin-23, interleukin-17, interleukin-10 and transforming growth factor- β levels at baseline and follow up visit. Patients were grouped into active and stable disease based on Indian Takyasu Arteritis clinical Activity Score-2010. Serum levels of these cytokines between active and stable disease and between baseline and follow up visits were compared by non-parametric tests. Results: Among 32 patients enrolled, 15 were classified as active while 17 as stable disease at baseline. IFN-γ levels were significantly higher in active disease than stable disease (p=0.0129) while other cytokines did not differ significantly between 2 groups. Serum levels of none of the cytokines changed significantly over 2 visits in both responders and non-responders. IL23 levels positively correlate with disease duration ((r=0.999; p<0.005). Modest correlation was observed between IFN-γ and IL23 levels at both baseline and follow up and between IFN-γ and IL-6 and CRP at follow up. Conclusion: IFN-γ levels are raised in active disease in TA and correlates well with other biomarkers of disease activity and proinflammatory cytokines. There is also a direct correlation between Il-23 levels and disease duration.

  7. A free terminal ileal perforation from active crohn disease in pregnancy: a diagnostic challenge.

    PubMed

    Philip, Sunu; Kamyab, Armin; Orfanou, Paraskevi

    2015-03-01

    The surgical management of the complications of Crohn disease is often challenging. These difficulties are compounded in pregnancy by competing interests of the mother and the baby. In this report, we describe the presentation and surgical management of a patient in her second trimester with active Crohn disease who required emergent surgical intervention. She had presented with the uncommon complication of a free perforation in the presence of active untreated disease.

  8. Activities of daily living and quality of life in Alzheimer disease.

    PubMed

    Opara, J A

    2012-06-12

    Alzheimer's disease is known for placing a significant burden on caregivers, which includes social, psychological, physical or economic aspects. The disease decreases patients' capacity for activities of daily living and quality of life. Information about functional status is useful in the interpretation of the quality of life assessment results. In this paper the most commonly used scales evaluating activities of daily living and quality of life in Alzheimer's disease, either generic or specific, is presented.

  9. An early and late peak in microglial activation in Alzheimer's disease trajectory.

    PubMed

    Fan, Zhen; Brooks, David J; Okello, Aren; Edison, Paul

    2017-01-24

    Amyloid-β deposition, neuroinflammation and tau tangle formation all play a significant role in Alzheimer's disease. We hypothesized that there is microglial activation early on in Alzheimer's disease trajectory, where in the initial phase, microglia may be trying to repair the damage, while later on in the disease these microglia could be ineffective and produce proinflammatory cytokines leading to progressive neuronal damage. In this longitudinal study, we have evaluated the temporal profile of microglial activation and its relationship between fibrillar amyloid load at baseline and follow-up in subjects with mild cognitive impairment, and this was compared with subjects with Alzheimer's disease. Thirty subjects (eight mild cognitive impairment, eight Alzheimer's disease and 14 controls) aged between 54 and 77 years underwent (11)C-(R)PK11195, (11)C-PIB positron emission tomography and magnetic resonance imaging scans. Patients were followed-up after 14 ± 4 months. Region of interest and Statistical Parametric Mapping analysis were used to determine longitudinal alterations. Single subject analysis was performed to evaluate the individualized pathological changes over time. Correlations between levels of microglial activation and amyloid deposition at a voxel level were assessed using Biological Parametric Mapping. We demonstrated that both baseline and follow-up microglial activation in the mild cognitive impairment cohort compared to controls were increased by 41% and 21%, respectively. There was a longitudinal reduction of 18% in microglial activation in mild cognitive impairment cohort over 14 months, which was associated with a mild elevation in fibrillar amyloid load. Cortical clusters of microglial activation and amyloid deposition spatially overlapped in the subjects with mild cognitive impairment. Baseline microglial activation was increased by 36% in Alzheimer's disease subjects compared with controls. Longitudinally, Alzheimer's disease subjects

  10. δ-Aminolevulinate Dehydratase Activity is Stimulated in a MPTP Mouse Model of Parkinson's Disease: Correlation with Myeloperoxidase Activity.

    PubMed

    Sampaio, Tuane Bazanella; Marcondes Sari, Marcel Henrique; Pesarico, Ana Paula; Nogueira, Cristina Wayne

    2016-09-21

    Myeloperoxidase (MPO) is an inducible heme peroxidase responsive to some stress situations. It is already known that its activity is stimulated in neurodegenerative disorders and in the animal model of parkinson's disease (PD) induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). By contrast, the role of δ-aminolevulinate dehydratase (δ-ALA-D), an essential enzyme for heme synthesis, has not been investigated in the MPTP model. The aim of this study was to investigate the involvement of striatal δ-ALA-D activity in an acute model of PD, induced by MPTP, in C57Bl/6 mice and its correlation with MPO activity. Animals received four MPTP injections (20 mg/kg, i.p.) or saline (vehicle) to induce a PD model. 7 days after MPTP administration, the motor function was evaluated through rotarod and challenging beam tests in mice. Afterward, mice were killed, and the striata were removed for biochemical analyses. MPTP-treated mice showed impairment in motor skills, such as balance and motor coordination. Furthermore, there was a reduction of tyrosine hydroxylase levels in these animals, which characterizes the dopaminergic lesion. Striatal δ-ALA-D activity was stimulated by MPTP, as well as the MPO activity, and a significant positive correlation between δ-ALA-D and MPO activities was also demonstrated. These data suggest that δ-ALA-D activity could be stimulated due to the requirement of heme groups by peroxidases. Therefore, this study demonstrated for the first time the involvement of striatal δ-ALA-D activity in the MPTP model and its correlation with the MPO activity.

  11. Systematic review of patient-reported outcome measures (PROMs) for assessing disease activity in rheumatoid arthritis

    PubMed Central

    de Jonge, Marieke J; Fransen, Jaap; Kievit, Wietske; van Riel, Piet LCM

    2016-01-01

    Patient assessment of disease activity in rheumatoid arthritis (RA) may be useful in clinical practice, offering a patient-friendly, location independent, and a time-efficient and cost-efficient means of monitoring the disease. The objective of this study was to identify patient-reported outcome measures (PROMs) to assess disease activity in RA and to evaluate the measurement properties of these measures. Systematic literature searches were performed in the PubMed and EMBASE databases to identify articles reporting on clinimetric development or evaluation of PROM-based instruments to monitor disease activity in patients with RA. 2 reviewers independently selected articles for review and assessed their methodological quality based on the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) recommendations. A total of 424 abstracts were retrieved for review. Of these abstracts, 56 were selected for reviewing the full article and 34 articles, presenting 17 different PROMs, were finally included. Identified were: Rheumatoid Arthritis Disease Activity Index (RADAI), RADAI-5, Patient-based Disease Activity Score (PDAS) I & II, Patient-derived Disease Activity Score with 28-joint counts (Pt-DAS28), Patient-derived Simplified Disease Activity Index (Pt-SDAI), Global Arthritis Score (GAS), Patient Activity Score (PAS) I & II, Routine Assessment of Patient Index Data (RAPID) 2–5, Patient Reported Outcome-index (PRO-index) continuous (C) & majority (M), Patient Reported Outcome CLinical ARthritis Activity (PRO-CLARA). The quality of reports varied from poor to good. Typically 5 out of 10 clinimetric domains were covered in the validations of the different instruments. The quality and extent of clinimetric validation varied among PROMs of RA disease activity. The Pt-DAS28, RADAI, RADAI-5 and RAPID 3 had the strongest and most extensive validation. The measurement properties least reported and in need of more evidence were: reliability

  12. Progesterone Alters Kynurenine Pathway Activation in IFN-γ-Activated Macrophages – Relevance for Neuroinflammatory Diseases

    PubMed Central

    de Bie, J.; Lim, C. K.; Guillemin, G. J.

    2016-01-01

    We have previously demonstrated that the kynurenine pathway (KP), the major biochemical pathway for tryptophan metabolism, is dysregulated in many inflammatory disorders that are often associated with sexual dimorphisms. We aimed to identify a potential functional interaction between the KP and gonadal hormones. We have treated primary human macrophages with progesterone in the presence and absence of inflammatory cytokine interferon-gamma (interferon-γ) that is known to be a potent inducer of regulating the KP enzyme. We found that progesterone attenuates interferon-γ-induced KP activity, decreases the levels of the excitotoxin quinolinic acid, and increases the neuroprotective kynurenic acid levels. We also showed that progesterone was able to reduce the inflammatory marker neopterin. These results may shed light on the gender disparity in response to inflammation. PMID:27980422

  13. Alterations in brain activation during cholinergic enhancement with rivastigmine in Alzheimer's disease

    PubMed Central

    Rombouts, S; Barkhof, F; van Meel, C S; Scheltens, P

    2002-01-01

    Background: Rivastigmine enhances cholinergic activity and has been shown in clinical trials to decrease the rate of deterioration in Alzheimer's disease. It remains unclear where in the brain it exerts its effect. Functional magnetic resonance imaging (fMRI) can be used to measure changes in brain function and relate these to cognition. Objectives: To use fMRI to study brain activation with rivastigmine treatment. Methods: The effect on brain activation of a single dose of rivastigmine was tested in seven patients with mild Alzheimer's disease using fMRI during face encoding, and in five patients during a parametric working memory task. Results: During face encoding, rivastigmine increased bilateral activation in the fusiform gyrus. Brain activation was also enhanced in the prefrontal cortex in a simple working memory task. When working memory load was further increased, not only was increased activation seen, but in certain areas there was also decreased activation. Conclusions: These findings link the previously observed increase in cognitive performance in Alzheimer's disease after treatment with a cholinesterase inhibitor to altered brain activation. Although the results cannot be generalised to the Alzheimer's disease population at large, they provide evidence that in mild Alzheimer's disease, rivastigmine enhances brain activation in the fusiform and frontal cortices. This is compatible with the concept of cholinergic circuitry. PMID:12438467

  14. A comparative study of metronidazole and sulfasalazine for active Crohn's disease: the cooperative Crohn's disease study in Sweden. II. Result.

    PubMed

    Ursing, B; Alm, T; Bárány, F; Bergelin, I; Ganrot-Norlin, K; Hoevels, J; Huitfeldt, B; Järnerot, G; Krause, U; Krook, A; Lindström, B; Nordle, O; Rosén, A

    1982-09-01

    Seventy-eight patients with active Crohn's disease participated in a randomized, double-blind, cross-over trial. The study comprised two 4-mo period. The purpose was to test the efficacy of metronidazole in comparison with that of sulfasalazine. As the main evaluation criteria the Crohn's Disease Activity Index and plasma levels of orosomucoid were chosen. In the first period no difference in efficacy as measured by Crohn's Disease Activity Index was found between the treatment groups. The reduction of the plasma orosomucoid level was significantly more pronounced in the metronidazole group. The hemoglobin concentration increased more in this group than in the sulfasalazine group, possibly due to a toxic effect of sulfasalazine. The erythrocyte sedimentation rate decreased similarly with both drugs. In 15 patients who had active disease throughout the first period, Crohn's Disease Activity Index decreased significantly in the second period for those who switched to metronidazole, but not for those who switched to sulfasalazine. After crossover, no apparent further change in Crohn's Disease Activity Index occurred in either of the treatment groups among patients who had responded favorably in the first period. The plasma concentration of orosomucoid increased significantly among the patients in the sulfasalazine group but not in the metronidazole group. It is therefore concluded that metronidazole is slightly more effective than sulfasalazine in the treatment of crohn's disease. It is worthwhile switching the drug regimen from sulfasalazine, when it fails, to metronidazole, but not from metronidazole to sulfasalazine.

  15. A Study on Association between Common Haematological Parameters and Disease Activity in Rheumatoid Arthritis

    PubMed Central

    Barui, Gopinath; Adhikari, Anjan; Karmakar, Rupam; Ghosh, Udas Chandra; Das, Tushar Kanti

    2017-01-01

    Introduction Rheumatoid Arthritis (RA) is a chronic systemic inflammatory disease where assessment of disease activity is essential for management of patient. Currently, many composite scoring systems are used for evaluation of disease activity but they are mainly clinical-based. As several haematological parameters are altered due to systemic inflammatory process in RA, this study was intended to evaluate role of common haematological parameters to assess disease activity in RA. Aim To find out the association of disease activity of Rheumatoid Arthritis (RA) with platelet count, Mean Platelet Volume (MPV) and Haemoglobin (Hb) level so that these cost-effective haematological parameters can be used as additional factors to assess disease activity. Materials and Methods This hospital based cross-sectional study was done on newly diagnosed patients of RA along with age and sex matched healthy control population. Patients suffering from malignancies, renal failure, diabetes mellitus or RA patients on drug therapy were excluded. Clinically, disease activity of RA was measured using DAS 28-3 Score (Modified Disease Activity Score using three variables- tender joint count, swollen joint count and ESR). Haematological parameters were measured by automated cell counter. Results Total 80 cases were selected (60 female and 20 male). 48 patients with high disease activity (DAS 28-3>5.1) were labelled as Group-A and 32 with low to moderate disease activity (DAS 28-3 ≤5.1) as Group- B. Mean platelet count of patients of group A and group B were 4.53 lac/cmm and 2.17 lac/cmm respectively (p <0.001). MPV mean in group A and B were 11.86 fl and 10.19 fl respectively (p <0.001). Mean Hb (g/dl) was 10.05 and 12.25 for group A and B respectively (p=0.001) for male patients while in females it was 10.12 and 11.91 for group A and B, respectively (p=0.003). Mean platelet count and MPV in control population were 2.07 lac/cmm and 9.4 fl, respectively while mean Hb (g/dl) was 13.31 (male

  16. Value of Computerized Tomography Enterography in Predicting Crohn’s Disease Activity: Correlation with Crohn’s Disease Activity Index and C-Reactive Protein

    PubMed Central

    Park, Eun Kyung; Han, Na Yeon; Park, Beom Jin; Sung, Deuk Jae; Cho, Sung Beom; Jeen, Yoon Tae; Keum, Bora; Kim, Min Ju

    2016-01-01

    Background The accurate evaluation of Crohn’s disease activity is important for the treatment of the disease and for monitoring the response. Computerized tomography (CT) enterography is a useful imaging modality that reflects enteric inflammation, as well as extramural complications. Objectives The aim of this study was to evaluate the correlation between CT enterographic (CTE) findings of active Crohn’s disease and the Crohn’s disease activity index (CDAI) and C-reactive protein (CRP). Patients and Methods Fifty CT enterographies of 39 patients with Crohn’s disease in the small bowel were used in our study. The CDAI was assessed through clinical and laboratory variables. Multiple CT parameters, including mural hyperenhancement, mural thickness, mural stratification, comb sign, and mesenteric fat attenuation, were evaluated with a four-point scale. The presence or absence of enhanced lymph nodes, fibrofatty proliferation, sinus or fistula, abscess, and stricture were also assessed. Two gastrointestinal radiologists independently reviewed all CT images, and inter-observer agreement was examined. Correlations between CT findings, CRP, and CDAI were assessed using Spearman’s rank correlation and logistic regression analysis. To assess the predictive accuracy of the model, a receiver-operating characteristic curve analysis for the sum of CT enterographic scores was used. Results Mural hyperenhancement, mural thickness, comb sign, mesenteric fat density, and fibrofatty proliferation were significantly correlated with CDAI and CRP (P < 0.05). The binary logistic regression model demonstrated that mesenteric fat density, mural stratification, and the presence of enhanced lymph nodes (P < 0.05) had an influence on CDAI severity. The area under the receiver operating characteristic curve (AUROC) of the CTE index for predicting disease activity was 0.85. Using a cut-off value of 8, the sensitivity and negative predictive values were 95% and 94%, respectively

  17. Development and Retrospective Validation of the Juvenile Spondyloarthritis Disease Activity (JSpADA) Index

    PubMed Central

    Weiss, Pamela F.; Colbert, Robert A.; Xiao, Rui; Feudtner, Chris; Beukelman, Timothy; DeWitt, Esi Morgan; Pagnini, Ilaria; Wright, Tracey B.; Wallace, Carol A.

    2014-01-01

    Objectives To develop and validate a Juvenile Spondyloarthritis (JSpA) Disease Activity (JSpADA) index for use in clinical practice and research. Methods Using modified Delphi consensus techniques, ten items were selected by participants in the international pediatric rheumatology list-serve, the Childhood Arthritis and Rheumatology Research Alliance, and the list-serve for the Pediatric Section of the American College of Rheumatology. Validation was performed in a retrospective multicenter cohort of 243 children. Results 106 physicians representing 14 countries completed the initial questionnaire. Completion rates for the subsequent questionnaires were 84%, 75%, and 77% of the original respondents. Ten items reached 80% consensus: arthritis, enthesitis, patient pain assessment, inflammatory markers, morning stiffness, clinical sacroiliitis, uveitis, back mobility, and patient and physician assessments of disease activity. Two items were eliminated after item analysis (patient and physician assessments of disease activity). Factor analysis identified 3 primary domains that explain 58% of variance: peripheral disease, axial disease, and uveitis. Cronbach α coefficient was 0.66. The JSpADA had high or moderate correlations with the Juvenile Arthritis disease activity score (r=0.80), patient and physician assessments of disease activity (r=0.70 and 0.66), and the Childhood Health Assessment Questionnaire (r=0.56). The JSpADA discriminated well between subjects with active versus inactive disease (p<0.001) and was responsive to improvement or worsening in disease activity over time (p<0.001). Conclusion Using international input and consensus formation techniques, we developed and validated the first disease activity assessment for JSpA. Future studies should validate the JSpADA index in a prospective multi-center cohort. PMID:25047959

  18. The MicroActive project: automatic detection of disease-related molecular cell activity

    NASA Astrophysics Data System (ADS)

    Furuberg, Liv; Mielnik, Michal; Johansen, Ib-Rune; Voitel, Jörg; Gulliksen, Anja; Solli, Lars; Karlsen, Frank; Bayer, Tobias; Schönfeld, Friedhelm; Drese, Klaus; Keegan, Helen; Martin, Cara; O'Leary, John; Riegger, Lutz; Koltay, Peter

    2007-05-01

    The aim of the MicroActive project is to develop an instrument for molecular diagnostics. The instrument will first be tested for patient screening for a group of viruses causing cervical cancer. Two disposable polymer chips with reagents stored on-chip will be inserted into the instrument for each patient sample. The first chip performs sample preparation of the epithelial cervical cells while mRNA amplification and fluorescent detection takes place in the second chip. More than 10 different virus markers will be analysed in one chip. We report results on sub-functions of the amplification chip. The sample is split into smaller droplets, and the droplets move in parallel channels containing different dried reagents for the different analyses. We report experimental results on parallel droplet movement control using one external pump only, combined with hydrophobic valves. Valve burst pressures are controlled by geometry. We show droplet control using valves with burst pressures between 800 and 4500 Pa. We also monitored the re-hydration times for two necessary dried reagents. After sample insertion, uniform concentration of the reagents in the droplet was reached after respectively 60 s and 10 min. These times are acceptable for successful amplification. Finally we have shown positive amplification of HPV type 16 using dried enzymes stored in micro chambers.

  19. Evaluation of inflammatory activity in Crohn’s disease and ulcerative colitis

    PubMed Central

    Vilela, Eduardo Garcia; Torres, Henrique Osvaldo da Gama; Martins, Fabiana Paiva; Ferrari, Maria de Lourdes de Abreu; Andrade, Marcella Menezes; da Cunha, Aloísio Sales

    2012-01-01

    Crohn’s disease and ulcerative colitis evolve with a relapsing and remitting course. Determination of inflammatory state is crucial for the assessment of disease activity and for tailoring therapy. However, no simple diagnostic test for monitoring intestinal inflammation is available. Noninvasive markers give only indirect assessments of disease activity. Histopathological or endoscopical examinations accurately assess inflammatory activity, but they are invasive, time consuming and expensive and therefore are unsuitable for routine use. Imaging procedures are not applicable for ulcerative colitis. The usefulness of ultrasound and Doppler imaging in assessing disease activity is still a matter of discussion for Crohn’s disease, and an increased interest in computed tomography enterograph (CTE) has been seen, mainly because it can delineate the extent and severity of bowel wall inflammation, besides detecting extraluminal findings. Until now, the available data concerning the accuracy of magnetic resonance enterography in detecting disease activity is less than CTE. Due to this, clinical activity indices are still commonly used for both diseases. PMID:22408345

  20. Autoantibodies against neutrophils and monocytes: tool for diagnosis and marker of disease activity in Wegener's granulomatosis.

    PubMed

    van der Woude, F J; Rasmussen, N; Lobatto, S; Wiik, A; Permin, H; van Es, L A; van der Giessen, M; van der Hem, G K; The, T H

    1985-02-23

    Immunoglobulin G (IgG) autoantibodies against extranuclear components of polymorphonuclear granulocytes were detected in 25 of 27 serum samples from patients with active Wegener's granulomatosis and in only 4 of 32 samples from patients without signs of disease activity. In a prospective study of 19 patients these antibodies proved to be better markers of disease activity than several other laboratory measurements used previously. The autoantibodies were disease specific and the titres were related to the results of an in-vitro granulocyte phagocytosis test, in which 7S IgG antibodies were internalised after specific binding to the cell, resulting in gradual formation of ring-like cytoplasmic structures. This autoantibody may have a pathogenetic role in Wegener's granulomatosis. The detection of this antibody is valuable for diagnosis and estimation of disease activity.

  1. Daily energy expenditure, physical activity, and weight loss in Parkinson's disease patients

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Patients with Parkinson's disease (PD) commonly exhibit weight loss (WL) which investigators attribute to various factors, including elevated energy expenditure. We tested the hypothesis that daily energy expenditure (DEE) and its components, resting energy expenditure (REE) and physical activity (P...

  2. Main determinants of physical activity levels in individuals with Parkinson's disease.

    PubMed

    Lana, Raquel de Carvalho; de Araujo, Lysandra Nogueira; Cardoso, Francisco; Rodrigues-de-Paula, Fátima

    2016-02-01

    This study analyzed the relationship between patient characteristics, factors associated with Parkinson's disease (PD), and physical activity level of individuals affected by the disease. Forty-six volunteers with mild-to-moderate idiopathic PD were assessed using sections II/III of the Unified Parkinson's Disease Rating Scale and their motor functions were classified according to the modified Hoehn and Yahr (HY) scale. Data such as age, disease duration, the Human Activity Profile (HAP), the Fatigue Severity Scale were collected. Lower limb bradykinesia and clinical subtypes of PD were defined. Two models that explained 76% of the variance of the HAP were used. The first comprised age, ability to perform activities of daily living (ADL), and the HY scale; the second comprised age, ability to perform ADL, and lower limb bradykinesia. Possible modifiable factors such as the ability to perform ADL and lower limb bradykinesia were identified as predictors of physical activity level of individuals with PD.

  3. Persons with moderate Alzheimer's disease use simple technology aids to manage daily activities and leisure occupation.

    PubMed

    Lancioni, Giulio E; Singh, Nirbhay N; O'Reilly, Mark F; Sigafoos, Jeff; Renna, Caterina; Pinto, Katia; De Vanna, Floriana; Caffò, Alessandro O; Stasolla, Fabrizio

    2014-09-01

    Two studies assessed technology-aided programs to support performance of daily activities and selection/activation of music items with patients with moderate Alzheimer's disease. In Study I, four patients were presented with activity-related pictorial instructions via a computer fitted with inexpensive, commercial software. In Study II, four patients were (a) presented with different music options and (b) allowed to select and activate the preferred option via a microswitch response. Study I showed that each patient learned to perform the two activities available with percentages of correct responses exceeding 85 by the end of the intervention. Study II showed that all patients learned to choose and activate music options. Psychology students, employed in a social validation check, scored the patients' behavior within the program better than their behavior in a control situation. The relevance and usability of simplified pictorial-instruction programs and music choice programs for patients with moderate Alzheimer's disease were discussed.

  4. Validity of a Questionnaire to Assess the Physical Activity Level in Coronary Artery Disease Patients

    ERIC Educational Resources Information Center

    Guiraud, Thibaut; Granger, Richard; Bousquet, Marc; Gremeaux, Vincent

    2012-01-01

    The aim of the study is to compare, in coronary artery disease patients, physical activity (PA) assessed with the Dijon Physical Activity Questionnaire (DPAQ) and the true PA objectively measured using an accelerometer. Seventy patients wore an accelerometer (MyWellness Key actimeter) throughout 1 week after a cardiac rehabilitation program that…

  5. 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

  6. Implementation of the Simple Endoscopic Activity Score in Crohn's Disease

    PubMed Central

    Koutroumpakis, Efstratios; Katsanos, Konstantinos H.

    2016-01-01

    Simple Endoscopic Score for Crohn's Disease (SES-CD) was developed as an attempt to simplify Crohn's Disease Endoscopic Index of Severity (CDEIS). Since it was constructed from CDEIS, SES-CD performs comparably but also carries similar limitations. Several studies have utilized SES-CD scoring to describe disease severity or response to therapy. Some of them used SES-CD score as a continuous variable while others utilized certain cutoff values to define severity grades. All SES-CD cutoff values reported in published clinical trials were empirically selected by experts. Although in most of the studies that used SEC-CD scoring to define disease severity, a score <3 reflected inactive disease, no study is using score 0 to predefine inactivity. Studies applying SES-CD to define response to treatment used score 0. There is no optimal SES-CD cut-off for endoscopic remission. The quantification of mucosal healing using SES-CD scoring has not been standardized yet. As the definition of mucosal healing by SES-CD is unset, the concept of deep remission is also still evolving. Serum and fecal biomarkers as well as new radiologic imaging techniques are complementary to SES-CD. Current practice as well as important changes in endoscopy should be taken into consideration when defining SES-CD cutoffs. The optimal timing of SES-CD scoring to assess mucosal healing is not defined yet. To conclude, SES-CD represents a valuable tool. However, a consensus agreement on its optimal use is required. PMID:27184635

  7. Rapid fecal calprotectin testing to assess for endoscopic disease activity in inflammatory bowel disease: A diagnostic cohort study

    PubMed Central

    Kwapisz, Lukasz; Mosli, Mahmoud; Chande, Nilesh; Yan, Brian; Beaton, Melanie; Micsko, Jessica; Mennill, Pauline W.; Barnett, William; Bax, Kevin; Ponich, Terry; Howard, John; Tirolese, Anthony; Lannigan, Robert; Gregor, James

    2015-01-01

    Background and Aim: With increasing numbers of patients diagnosed with inflammatory bowel disease (IBD), it is important to identify noninvasive methods of detecting disease activity. The aim of this study is to examine the diagnostic accuracy of fecal rapid calprotectin (FC) testing in the detection of endoscopically active IBD. Patients and Methods: All consecutive patients presenting to outpatient clinics with lower gastrointestinal symptoms were prospectively recruited. Patients provided FC samples. Sensitivity (Sn), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV) for FC were calculated. Receiver–operator characteristics (ROC) curve was used to identify the ideal FC cutoff that predicts endoscopic disease activity. Correlation between FC and endoscopic disease activity, disease location, and C-reactive protein (CRP) levels were measured. Results: One hundred and twenty-six patients, of whom 52% were females, were included in the final analysis with a mean age of 44.4 ± 16.7 years. Comparing FC to endoscopic findings, the following results were calculated: A cutoff point of 100 μg/g showed Sn = 83%, Sp = 67%, PPV = 65%, and NPV = 85%; and 200 μg/g showed Sn = 66%, Sp = 82%, PPV = 73%, and NPV = 77%. Based on ROC curve, the best FC cutoff point to predict endoscopic disease activity was 140 μg/g. Using this reference, FC levels strongly correlated with colorectal, ileocolonic, and ileal disease and predicted endoscopic activity. Conclusions: FC is an accurate test when used as an initial screening tool for patients suspected of having active IBD. Given its noninvasive nature, it may prove to reduce the need for colonoscopy and be an added tool in the management of IBD. PMID:26655130

  8. The relationship between infliximab concentrations, antibodies to infliximab and disease activity in Crohn's disease

    PubMed Central

    Vande Casteele, Niels; Khanna, Reena; Levesque, Barrett G; Stitt, Larry; Zou, G Y; Singh, Sharat; Lockton, Steve; Hauenstein, Scott; Ohrmund, Linda; Greenberg, Gordon R; Rutgeerts, Paul J; Gils, Ann; Sandborn, William J; Vermeire, Séverine; Feagan, Brian G

    2015-01-01

    Objective Although low infliximab trough concentrations and antibodies to infliximab (ATI) are associated with poor outcomes in patients with Crohn's disease (CD), the clinical relevance of ATI in patients with adequate infliximab concentrations is uncertain. We evaluated this question using an assay sensitive for identification of ATI in the presence of infliximab. Design In an observational study, 1487 trough serum samples from 483 patients with CD who participated in four clinical studies of maintenance infliximab therapy were analysed using a fluid phase mobility shift assay. Infliximab and ATI concentrations most discriminant for remission, defined as a C-reactive protein concentration of ≤5 mg/L, were determined by receiver operating characteristic curves. A multivariable regression model evaluated these factors as independent predictors of remission. Results Based upon analysis of 1487 samples, 77.1% of patients had detectable and 22.9% had undetectable infliximab concentrations, of which 9.5% and 71.8%, respectively, were positive for ATI. An infliximab concentration of >2.79 μg/mL (area under the curve (AUC)=0.681; 95% CI 0.632 to 0.731) and ATI concentration of <3.15 U/mL (AUC=0.632; 95% CI 0.589 to 0.676) were associated with remission. Multivariable analysis showed that concentrations of both infliximab trough (OR 1.8; 95% CI 1.3 to 2.5; p<0.001) and ATI (OR 0.57; 95% CI 0.39 to 0.81; p=0.002) were independent predictors of remission. Conclusions The development of ATI increases the probability of active disease even at low concentrations and in the presence of a therapeutic concentration of drug during infliximab maintenance therapy. Evaluation of strategies to prevent ATI formation, including therapeutic drug monitoring with selective infliximab dose intensification, is needed. PMID:25336114

  9. Activity of Crohn's disease assessed by colour Doppler ultrasound analysis of the affected loops.

    PubMed

    Esteban, J M; Maldonado, L; Sanchiz, V; Minguez, M; Benages, A

    2001-01-01

    The aim of this study was to evaluate with colour Doppler ultrasound the vascular changes in the wall of the loops affected by Crohn's disease, and to establish whether these changes reflects clinical or biochemical activity of Crohn's disease. Seventy-nine patients with Crohn's disease (44 with active disease and 35 inactive patients) were studied with frequency- and amplitude-encoded duplex Doppler sonography. A group of 35 healthy volunteers were also included. The exam consisted of the search for colour signals in the walls of the loops affected by Crohn's disease, classifying the degree of vascularity with a simple scoring system into three groups: absence of colour signal (score of 0); weak or scattered colour signals (score of 1); and multiple colour signals or clear identification of vessels in the loops walls (score of 2). Doppler curves were obtained of the detected vessels with measurement of the resistive index (RI). There was a visible increase in the gut walls' vascularity in the active patients compared with those with inactive disease. The mean RI was statistically significantly lower in the gut wall vessels of the patients with active illness than that obtained in the inactive patients. Colour Doppler ultrasound is a useful tool in the assessment of activity in Crohn's disease.

  10. Serum calreticulin as a novel biomarker of juvenile idiopathic arthritis disease activity

    PubMed Central

    Hashaad, Nashwa Ismail; Fawzy, Rasha Mohamed; Elazem, Abeer Ahmed Abo; Youssef, Mohamed Ibrahim

    2017-01-01

    Objective This study aimed to investigate the relations between calreticulin (CRT) serum level and both disease activity and severity parameters in juvenile idiopathic arthritis (JIA). Material and Methods In this study, 60 children with JIA and 50 age-and-sex-matched healthy subjects were enrolled. The assessment of the disease activity was done using juvenile arthritis disease activity score 27 (JADAS-27). The assessment of disease severity was done via gray-scale ultrasonography (US) and power Doppler US (PDUS). Enzyme-linked immunosorbent assay (ELISA) was used to assay the serum level of human CRT. Results The mean serum CRT levels in JIA patients was 8.6±1.2 ng/mL and showed a highly significant increase (p=0.001) as compared to the mean serum levels in the controls (5.02±0.77 ng/mL). There were statistically significant positive correlations between the serum CRT levels and disease duration, tender joint count, swollen joint count, visual analog scale, erythrocyte sedimentation rate, JADAS-27, C-reactive protein, rheumatoid factor titer, and ultrasonographic grading for synovitis and neovascularization. Conclusion Elevated serum CRT levels in JIA patients and its correlations with JIA disease activity and severity parameters signified that CRT might be used as a novel biomarker for disease activity and severity in JIA. PMID:28293448

  11. Gut microbiome composition and function in experimental colitis during active disease and treatment-induced remission

    PubMed Central

    Rooks, Michelle G; Veiga, Patrick; Wardwell-Scott, Leslie H; Tickle, Timothy; Segata, Nicola; Michaud, Monia; Gallini, Carey Ann; Beal, Chloé; van Hylckama-Vlieg, Johan ET; Ballal, Sonia A; Morgan, Xochitl C; Glickman, Jonathan N; Gevers, Dirk; Huttenhower, Curtis; Garrett, Wendy S

    2014-01-01

    Dysregulated immune responses to gut microbes are central to inflammatory bowel disease (IBD), and gut microbial activity can fuel chronic inflammation. Examining how IBD-directed therapies influence gut microbiomes may identify microbial community features integral to mitigating disease and maintaining health. However, IBD patients often receive multiple treatments during disease flares, confounding such analyses. Preclinical models of IBD with well-defined disease courses and opportunities for controlled treatment exposures provide a valuable solution. Here, we surveyed the gut microbiome of the T-bet−/− Rag2−/− mouse model of colitis during active disease and treatment-induced remission. Microbial features modified among these conditions included altered potential for carbohydrate and energy metabolism and bacterial pathogenesis, specifically cell motility and signal transduction pathways. We also observed an increased capacity for xenobiotics metabolism, including benzoate degradation, a pathway linking host adrenergic stress with enhanced bacterial virulence, and found decreased levels of fecal dopamine in active colitis. When transferred to gnotobiotic mice, gut microbiomes from mice with active disease versus treatment-induced remission elicited varying degrees of colitis. Thus, our study provides insight into specific microbial clades and pathways associated with health, active disease and treatment interventions in a mouse model of colitis. PMID:24500617

  12. Relationship of lipoprotein(a) levels to physical activity and family history of coronary heart disease.

    PubMed Central

    Martín, S; Elosua, R; Covas, M I; Pavesi, M; Vila, J; Marrugat, J

    1999-01-01

    OBJECTIVES: This study evaluated the association of physical activity with serum lipoprotein(a) [La(a)] levels in individuals according to whether they had a family history of coronary heart disease (CHD). METHODS: Lp(a) levels in 332 healthy Spanish men aged 20 to 60 years were measured. Physical activity and family history of CHD were assessed. RESULTS: For men with a family history of CHD, the odds ratio for Lp(a) levels above the median value was 0.13 (95% confidence interval = 0.03, 0.50) in very active men (energy expended in physical activity > 300 kcal/day) compared with active men (energy expended in physical activity < 300 kcal/day). CONCLUSIONS: Regular daily physical activity in individuals with a family history of CHD could be useful for controlling Lp(a) levels. PMID:10076490

  13. Staying Active: Physical Activity and Exercise

    MedlinePlus

    ... How much physical activity should I do each week? The Centers for Disease Control and Prevention recommend ... 150 minutes of moderate-intensity aerobic activity a week, along with muscle-strengthening activities on 2 days ...

  14. Measuring the Activity of Leucine-Rich Repeat Kinase 2: A Kinase Involved in Parkinson's Disease

    PubMed Central

    Lee, Byoung Dae; Li, Xiaojie; Dawson, Ted M.; Dawson, Valina L.

    2015-01-01

    Mutations in the LRRK2 (Leucine-Rich Repeat Kinase 2) gene are the most common cause of autosomal dominant Parkinson's disease. LRRK2 has multiple functional domains including a kinase domain. The kinase activity of LRRK2 is implicated in the pathogenesis of Parkinson's disease. Developing an assay to understand the mechanisms of LRRK2 kinase activity is important for the development of pharmacologic and therapeutic applications. Here, we describe how to measure in vitro LRRK2 kinase activity and its inhibition. PMID:21960214

  15. Association of nailfold capillary changes with disease activity, clinical and laboratory findings in patients with dermatomyositis

    PubMed Central

    Shenavandeh, Saeedeh; Zarei Nezhad, Maryam

    2015-01-01

    Background: The present study aimed to investigate the Nailfold Capillaroscopy (NC) features of the patients with dermatomyositis (DM) and its correlation with their disease activity indices, physical findings, and laboratory results. Methods: The present cross-sectional study was conducted on 27 DM patients above 16 years old who had referred to an(there are 3 clinics not one) outpatient rheumatology clinics from 2012 to 2013. Nailfold capillaroscopy and calculation of disease activity indices were performed separately for all the patients by two rheumatologists who were blinded to each other's results. Statistical analyses were performed using chi-square and Mann-Whitney U tests. Results: The mean age of the patients was 39.2±14.1 years with the mean disease duration of 13.1±15.2 months (range: 1-72 months). Myopathic electromyography (EMG) findings showed a strong association with scleroderma pattern (p=0.015). However, disease activity in each organ system and global disease activity showed no significant association between scleroderma pattern and other NC findings. (Disease activity in each organ system and also global disease activity were both assessed to see if they are associated with scleroderma pattern and other NC findings so if we use between it means we are looking for an association between scleroderma pattern and other NC findings and this is not what we have done and is wrong.) Conclusion: This study revealed no significant relationship between disease activity indices and NC features. Thus, it may be more precise to interpret the results of NC in conjunction with other physical and laboratory findings. PMID:26793626

  16. 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

  17. Stressful life events and psychosocial correlates of pediatric inflammatory bowel disease activity

    PubMed Central

    Giannakopoulos, George; Chouliaras, George; Margoni, Daphne; Korlou, Sophia; Hantzara, Vassiliki; Panayotou, Ioanna; Roma, Eleftheria; Liakopoulou, Magda; Anagnostopoulos, Dimitris C

    2016-01-01

    AIM To investigate the association of psychiatric and psychosocial correlates with inflammatory bowel disease (IBD) activity in children and adolescents. METHODS A total of 85 pediatric IBD patients (in remission or active state of the disease) and their parents completed a series of questionnaires and semi-structured interviews measuring life events, depression, anxiety, family dysfunction, and parent mental health. Differences between the remission and the IBD active group and the association of any significant variable with the disease activity state were examined. RESULTS Parents of children being in active state of the disease reported more life events (P = 0.005) and stressful life events (P = 0.048) during the past year and more mental health symptoms (P < 0.001), while the children themselves reported higher levels of anxiety symptoms (P = 0.017) compared to the remission group. In the logistic regression multivariate analysis, the only predictor which had a significant positive effect on the probability of the patients being in active state was parent mental health symptoms (OR = 4.8; 95%CI: 1.2-25.8). CONCLUSION Life events, child anxiety and parent mental health symptoms may be important correlates of pediatric IBD activity and targets of thorough assessment and treatment. PMID:27679771

  18. Health-related quality of life in adolescents with inflammatory bowel disease depends on disease activity and psychiatric comorbidity.

    PubMed

    Engelmann, G; Erhard, D; Petersen, M; Parzer, P; Schlarb, A A; Resch, F; Brunner, R; Hoffmann, G F; Lenhartz, H; Richterich, A

    2015-04-01

    Adolescent patients with inflammatory bowel disease (IBD) show an increased risk for behavioral and emotional dysfunction. Health-related quality of life (HRQoL) is influenced by medical illnesses, as well as by psychiatric disorders, but for adolescents with IBD, the extent to which HRQoL is influenced by these two factors is unclear. For 47 adolescent IBD patients, we analyzed disease activity, HRQoL and whether or not a psychiatric disorder was present. Disease activity was estimated using pediatric Ulcerative Colitis Activity Index and pediatric Crohn's Disease Activity Index. The IMPACT-III and the EQ-5D were used to measure HRQoL and QoL, respectively. In addition, patient and parent diagnostic interviews were performed. 55.3 % patients fulfilled DSM-IV criteria for one or more psychiatric disorders. In all patients, psychiatric comorbidity together with disease activity contributed to a reduction in quality of life. Adolescents with IBD are at a high risk for clinically relevant emotional or behavioral problems resulting in significantly lower HRQoL. We conclude that accessible, optimally structured psychotherapeutic and/or psychiatric help is needed in adolescent patients with IBD.

  19. Sport for All: Physical Activity and the Prevention of Disease. Facts and Figures.

    ERIC Educational Resources Information Center

    Reville, Ph.

    The material presented in this booklet is concerned with the impact of physical activity practiced by the general public, irrespective of age and sex, of various North American and European countries. Major emphasis is on the individual's physical health and susceptibility to disease. Chapter one discusses diseases which occur most frequently in…

  20. Colonic localization of indium-111 labeled leukocytes in active Behcet's disease

    SciTech Connect

    Harre, R.G.; Conrad, G.R.; Seabold, J.E.

    1988-06-01

    A patient with known Behcet's disease demonstrated intense colonic localization of In-111 labeled leukocytes. Gastrointestinal involvement had not been previously manifested, but extensive colonic inflammation was documented by endoscopy. This case illustrates the utility of In-111 labeled leukocyte imaging for detecting active bowel disease in a debilitated patient with documented Behcet's vasculitis.

  1. Indices of free radical activity in the cerebrospinal fluid in motor neuron disease.

    PubMed Central

    Mitchell, J D; Jackson, M J; Pentland, B

    1987-01-01

    Indices of free-radical activity and lipid peroxidation were studied in cerebrospinal fluid samples obtained from 11 patients with motor neuron disease and 11 reference subjects. No differences were found between the two groups. The significance of this finding is discussed in relation to current views of the possible pathogenesis of this disease. PMID:3625217

  2. Penicillin Use in Meningococcal Disease Management: Active Bacterial Core Surveillance Sites, 2009

    PubMed Central

    Blain, Amy E.; Mandal, Sema; Wu, Henry; MacNeil, Jessica R.; Harrison, Lee H.; Farley, Monica M.; Lynfield, Ruth; Miller, Lisa; Nichols, Megin; Petit, Sue; Reingold, Arthur; Schaffner, William; Thomas, Ann; Zansky, Shelley M.; Anderson, Raydel; Harcourt, Brian H.; Mayer, Leonard W.; Clark, Thomas A.; Cohn, Amanda C.

    2016-01-01

    In 2009, in the Active Bacterial Core surveillance sites, penicillin was not commonly used to treat meningococcal disease. This is likely because of inconsistent availability of antimicrobial susceptibility testing and ease of use of third-generation cephalosporins. Consideration of current practices may inform future meningococcal disease management guidelines. PMID:27704009

  3. Predictors of Alzheimer's Disease Caregiver Depression and Burden: What Noncaregiving Adults Can Learn from Active Caregivers

    ERIC Educational Resources Information Center

    Hayslip, Bert, Jr.; Han, GiBaeg; Anderson, Cristina L.

    2008-01-01

    This study examined similarities and differences between active caregivers (adult children and spouses whose family member had Alzheimer's disease) and not-as-yet caregiving adults (adult children and spouses whose family members are older, but do not as yet suffer from Alzheimer's disease). The objective was to determine what factors predict…

  4. Penicillin Use in Meningococcal Disease Management: Active Bacterial Core Surveillance Sites, 2009.

    PubMed

    Blain, Amy E; Mandal, Sema; Wu, Henry; MacNeil, Jessica R; Harrison, Lee H; Farley, Monica M; Lynfield, Ruth; Miller, Lisa; Nichols, Megin; Petit, Sue; Reingold, Arthur; Schaffner, William; Thomas, Ann; Zansky, Shelley M; Anderson, Raydel; Harcourt, Brian H; Mayer, Leonard W; Clark, Thomas A; Cohn, Amanda C

    2016-09-01

    In 2009, in the Active Bacterial Core surveillance sites, penicillin was not commonly used to treat meningococcal disease. This is likely because of inconsistent availability of antimicrobial susceptibility testing and ease of use of third-generation cephalosporins. Consideration of current practices may inform future meningococcal disease management guidelines.

  5. Hepatic alcohol dehydrogenase activity in alcoholic subjects with and without liver disease.

    PubMed Central

    Vidal, F; Perez, J; Morancho, J; Pinto, B; Richart, C

    1990-01-01

    Alcohol dehydrogenase activity was measured in samples of liver tissue from a group of alcoholic and non-alcoholic subjects to determine whether decreased liver alcohol dehydrogenase activity is a consequence of ethanol consumption or liver damage. The alcoholic patients were classified further into the following groups: control subjects with no liver disease (group 1), subjects with non-cirrhotic liver disease (group 2), and subjects with cirrhotic liver disease (group 3). The non-alcoholic subjects were also divided, using the same criteria, into groups 4, 5, and 6, respectively. The analysis of the results showed no significant differences when mean alcohol dehydrogenase activities of alcoholic and non-alcoholic patients with similar degrees of liver pathology were compared (groups 1 v 4, 2 v 5, and 3 v 6. Alcohol dehydrogenase activity was, however, severely reduced in patients with liver disease compared with control subjects. Our findings suggest that alcohol consumption does not modify hepatic alcohol dehydrogenase activity. The reduction in specific alcohol dehydrogenase activity in alcoholic liver disease is a consequence of liver damage. PMID:2379876

  6. Optimizing Rheumatoid Arthritis Therapy: Using Objective Measures of Disease Activity to Guide Treatment

    PubMed Central

    Owens, Gary M.

    2015-01-01

    Background Rheumatoid arthritis (RA) affects approximately 1.5 million individuals in the United States, or approximately 1% of the US adult population. In women, RA most often begins between age 30 and 60 years; in men, it often starts later in life. Patients with RA may have rapid declines in physical function that can begin early in the disease course. Disability increases most rapidly during the early years of the disease course, and if patients are not accurately diagnosed and do not receive appropriate care early, substantial functional declines may result. Objective To review strategies and clinical assessment tools that may optimize patient outcomes by using objective measures of disease activity. Discussion The goal of treatment for patients newly diagnosed with RA should be preventing joint damage from developing by employing early and aggressive approaches to therapy that minimize disease activity. Likewise, for established disease, treatment should be aimed at limiting the progression of existing joint damage. Substantial advances have been made in the treatment of RA over the past 2 decades, in large part as a result of better understanding of the biology of RA and the resultant introduction of biologic therapies. In 2010, an international task force published recommendations for a treat-to-target management approach to RA, much of which was based on the use of biologic drugs. This treatment strategy emphasized that the primary target in the treatment of patients with RA should be clinical remission or low disease activity. The tools necessary to measure RA disease activity are often incomplete, imprecise, or rely on a combination of physician and patient subjective evaluations. There is no one symptom, laboratory measure, or clinical tool that provides a truly accurate assessment of disease activity in patients with RA. Conclusion Thus, there is a large gap between what is recommended in clinical guidelines and the actual practice of rheumatologists

  7. Small molecule SIRT1 activators for the treatment of aging and age-related diseases

    PubMed Central

    Hubbard, Basil P.; Sinclair, David A.

    2014-01-01

    Recent studies in mice have identified single molecules that can delay multiple diseases of aging and extend lifespan. In theory, such molecules could prevent dozens of diseases simultaneously, significantly extending healthy years of life. In this review we discuss recent advances, controversies, opportunities, and challenges surrounding the development of SIRT1 activators, molecules with the potential to delay aging and age-related diseases. Sirtuins comprise a family of NAD+-dependent deacylases that are central to the body’s response to diet and exercise. New studies indicate that both natural and synthetic sirtuin activating compounds (STACs) work via a common allosteric mechanism to stimulate sirtuin activity, thereby conferring broad health benefits in rodents, primates, and possibly humans. The fact that the two-thirds of people in the USA who consume multiple dietary supplements consume resveratrol, a SIRT1 activator, underscores the importance of understanding the biochemical mechanism, physiological effects, and safety of STACs. PMID:24439680

  8. Selective hyposmia in Parkinson disease: association with hippocampal dopamine activity.

    PubMed

    Bohnen, Nicolaas I; Gedela, Satyanarayana; Herath, Priyantha; Constantine, Gregory M; Moore, Robert Y

    2008-12-05

    Olfactory dysfunction is common in patients with Parkinson disease (PD) and has been attributed to early pathological deposition of Lewy bodies and Lewy neurites in primary olfactory centers. However, olfactory deficits do not always worsen over time despite progression of disease raising the possibility of additional pathobiological mechanisms contributing to olfactory functions in PD, such as changes in olfactory neurotransmitter functions. Neurotransmitter changes, such as altered dopaminergic status, may also better explain the selective nature of odor identification deficits in PD. Proper odor identification depends on higher order structures, such as the hippocampus, for olfactory cognitive or memory processing. Using the University of Pennsylvania Smell Identification Test (UPSIT), we previously identified three odors (banana, licorice, dill pickle, labeled as UPSIT-3) that PD subjects most frequently failed to recognize compared to age- and gender-matched controls. We also identified six odors that were equally successfully identified by controls and PD subjects (NPD-Olf6). A ratio of UPSIT-3 divided by NPD-Olf6 scores provides another descriptor of selective hyposmia in PD ("olfactory ratio"). In this study we investigated the pathophysiology of hyposmia in PD using dopamine transporter (DAT) PET. Twenty-nine PD patients (Hoehn and Yahr stages I-III; 7f/22m; age 60.2+/-10.8) underwent olfactory testing using the UPSIT and [(11)C]beta-CFT DAT PET. DAT binding potentials (BP) were assessed in the hippocampus, amygdala, ventral and dorsal striatum. We found that correlation coefficients between total UPSIT scores and regional brain DAT BP were highest for the hippocampus (Rs=0.54, P=0.002) and lower for the amygdala (Rs=0.44, P=0.02), ventral (Rs=0.48, P=0.008) and dorsal striatum (Rs=0.39, P=0.03). Correlations were most significant for the selective hyposmia measures and hippocampal DAT: UPSIT-3 (Rs=0.65, P=0.0001) and the olfactory ratio (Rs=0.74, P<0

  9. EULAR Sjögren's syndrome disease activity index (ESSDAI): a user guide.

    PubMed

    Seror, Raphaèle; Bowman, Simon J; Brito-Zeron, Pilar; Theander, Elke; Bootsma, Hendrika; Tzioufas, Athanasios; Gottenberg, Jacques-Eric; Ramos-Casals, Manel; Dörner, Thomas; Ravaud, Philippe; Vitali, Claudio; Mariette, Xavier; Asmussen, Karsten; Jacobsen, Soren; Bartoloni, Elena; Gerli, Roberto; Bijlsma, Johannes Wj; Kruize, Aike A; Bombardieri, Stefano; Bookman, Arthur; Kallenberg, Cees; Meiners, Petra; Brun, Johan G; Jonsson, Roland; Caporali, Roberto; Carsons, Steven; De Vita, Salvatore; Del Papa, Nicoletta; Devauchelle, Valerie; Saraux, Alain; Fauchais, Anne-Laure; Sibilia, Jean; Hachulla, Eric; Illei, Gabor; Isenberg, David; Jones, Adrian; Manoussakis, Menelaos; Mandl, Thomas; Jacobsson, Lennart; Demoulins, Frederic; Montecucco, Carlomaurizio; Ng, Wan-Fai; Nishiyama, Sumusu; Omdal, Roald; Parke, Ann; Praprotnik, Sonja; Tomsic, Matjia; Price, Elizabeth; Scofield, Hal; L Sivils, Kathy; Smolen, Josef; Laqué, Roser Solans; Steinfeld, Serge; Sutcliffe, Nurhan; Sumida, Takayuki; Valesini, Guido; Valim, Valeria; Vivino, Frederick B; Vollenweider, Cristina

    2015-01-01

    The EULAR Sjögren's syndrome (SS) disease activity index (ESSDAI) is a systemic disease activity index that was designed to measure disease activity in patients with primary SS. With the growing use of the ESSDAI, some domains appear to be more challenging to rate than others. The ESSDAI is now in use as a gold standard to measure disease activity in clinical studies, and as an outcome measure, even a primary outcome measure, in current randomised clinical trials. Therefore, ensuring an accurate and reproducible rating of each domain, by providing a more detailed definition of each domain, has emerged as an urgent need. The purpose of the present article is to provide a user guide for the ESSDAI. This guide provides definitions and precisions on the rating of each domain. It also includes some minor improvement of the score to integrate advance in knowledge of disease manifestations. This user guide may help clinicians to use the ESSDAI, and increase the reliability of rating and consequently of the ability to detect true changes over time. This better appraisal of ESSDAI items, along with the recent definition of disease activity levels and minimal clinically important change, will improve the assessment of patients with primary SS and facilitate the demonstration of effectiveness of treatment for patients with primary SS.

  10. EULAR Sjögren's syndrome disease activity index (ESSDAI): a user guide

    PubMed Central

    Seror, Raphaèle; Bowman, Simon J; Brito-Zeron, Pilar; Theander, Elke; Bootsma, Hendrika; Tzioufas, Athanasios; Gottenberg, Jacques-Eric; Ramos-Casals, Manel; Dörner, Thomas; Ravaud, Philippe; Vitali, Claudio; Mariette, Xavier

    2015-01-01

    The EULAR Sjögren's syndrome (SS) disease activity index (ESSDAI) is a systemic disease activity index that was designed to measure disease activity in patients with primary SS. With the growing use of the ESSDAI, some domains appear to be more challenging to rate than others. The ESSDAI is now in use as a gold standard to measure disease activity in clinical studies, and as an outcome measure, even a primary outcome measure, in current randomised clinical trials. Therefore, ensuring an accurate and reproducible rating of each domain, by providing a more detailed definition of each domain, has emerged as an urgent need. The purpose of the present article is to provide a user guide for the ESSDAI. This guide provides definitions and precisions on the rating of each domain. It also includes some minor improvement of the score to integrate advance in knowledge of disease manifestations. This user guide may help clinicians to use the ESSDAI, and increase the reliability of rating and consequently of the ability to detect true changes over time. This better appraisal of ESSDAI items, along with the recent definition of disease activity levels and minimal clinically important change, will improve the assessment of patients with primary SS and facilitate the demonstration of effectiveness of treatment for patients with primary SS. PMID:26509054

  11. Active-R filter

    DOEpatents

    Soderstrand, Michael A.

    1976-01-01

    An operational amplifier-type active filter in which the only capacitor in the circuit is the compensating capacitance of the operational amplifiers, the various feedback and coupling elements being essentially solely resistive.

  12. Association of sleep quality in Behcet disease with disease activity, depression, and quality of life in Korean population

    PubMed Central

    Lee, Jimin; Kim, Sung-Soo; Jeong, Hye-Jin; Son, Chang-Nam; Kim, Ji-Min; Cho, Yong-Won; Kim, Sang-Hyon

    2017-01-01

    Background/Aims Sleep disturbance is prime concern in patients with Behcet disease. The purpose of this study was to find out the effects of sleep quality, in Korean patients suffering from Behcet disease. We further investigated the relationship between depression, quality of life and the clinical findings of Behcet disease. Methods The study was performed by the cross-sectional design. Sleep quality was assessed by the Korean version of Pittsburgh sleep quality index (PSQI). Disease activity of Behcet disease was evaluated by Behcet disease current activity form (BDCAF). Depression was assessed by the Korean version of Beck depression inventory second edition (BDI-2). Quality of life was assessed by the Korean version of the Leeds Behcet disease quality of life measure (BDQoL). Results Among the 100 patients studied, 42% reported poor sleep quality (PSQI ≥ 9). These patients have a higher BDI-2, total BDCAF and pain visual analogue scale (VAS) score (p < 0.001, p = 0.022, and p = 0.005). Considering BDCAF, the frequency of genital ulcer was significantly higher (p = 0.01). Behcet was higher in females. The BDQoL was lower in poor sleeper group (p = 0.004 and p < 0.001). Among 7 PSQI components, daytime dysfunction was higher in patients with high disease activity (p = 0.03). Total PSQI score were strongly correlated with BDCAF, BDI-2, BDQoL, and pain VAS score (p = 0.02, p < 0.001, p < 0.001, and p < 0.001, respectively). Conclusions Low sleep quality is directly associated with disease activity, depression, and quality of life in Korean patients with Behcet disease. PMID:28192886

  13. Effect of disease and drug treatment on blood serotonin and monoamine oxidase B activity in Parkinson's disease.

    PubMed

    van Kempen, G M; Janjua, R; Roos, R A

    1995-05-01

    Serotonin (5-hydroxytryptamine, 5HT) content and monoamine oxidase (MAO) activity were determined in whole blood of patients with Parkinson's disease (PD) with and without drug treatment and compared with controls. From that comparison a significant reduction in platelet 5HT became apparent in PD. Selegiline, which was always used in combination with L-dopa, not only inhibited MAO activity, as expected, but it also appeared to induce an increase in 5HT content.

  14. Primary Sjögren's syndrome--clinical and laboratory markers of disease activity.

    PubMed

    Oxholm, P

    1992-10-01

    Primary Sjögren's syndrome is a chronic autoimmune disorder of the lacrimal and salivary glands, reflecting general involvement of the exocrine tissues and leading to functional impairment. This polyglandular disease is often associated with systemic extraglandular manifestations, and laboratory tests usually indicate polyclonal B-lymphocyte hyperactivity. Clinical and laboratory markers monitoring the disease processes are needed for improved management of primary Sjögren's syndrome. However, incomplete knowledge of the long-term course of inflammation as well as of clinical manifestations makes precise and simple directions for monitoring disease activity in primary Sjögren's syndrome difficult. This review describes potential primary (eg, salivary gland histopathology, autoantibodies, soluble interleukin-2 receptors, and beta 2-microglobulin) and secondary disease activity markers (clinical and laboratory signs of glandular and extraglandular organ damage) and their known associations. The importance of genetic characteristics, patient age, and symptom duration for the disease activity markers is indicated. The systematic use of primary and secondary disease activity markers will improve our understanding of primary Sjögren's syndrome and help create better guidelines for monitoring the disease.

  15. Erythrocyte C3d and C4d for Monitoring Disease Activity in Systemic Lupus Erythematosus

    PubMed Central

    Kao, Amy H.; Navratil, Jeannine S.; Ruffing, Margie J.; Liu, Chau-Ching; Hawkins, Douglas; McKinnon, Kathleen M.; Danchenko, Natalya; Ahearn, Joseph M.; Manzi, Susan

    2010-01-01

    Objective Disease activity in systemic lupus erythematosus (SLE) is typically monitored by measuring serum C3 and C4. However, these proteins have limited utility as lupus biomarkers, because they are substrates rather than products of complement activation. The aim of this study was to evaluate the utility of measuring the erythrocyte-bound complement activation products, erythrocyte-bound C3d (E-C3d) and E-C4d, compared with that of serum C3 and C4 for monitoring disease activity in patients with SLE. Methods The levels of E-C3d and E-C4d were measured by flow cytometry in 157 patients with SLE, 290 patients with other diseases, and 256 healthy individuals. The patients with SLE were followed up longitudinally. Disease activity was measured at each visit, using the validated Systemic Lupus Activity Measure (SLAM) and the Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA) version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Results At baseline, patients with SLE had higher median levels of E-C3d and E-C4d (P < 0.0001) in addition to higher within-patient and between-patient variability in both E-C3d and E-C4d when compared with the 2 non-SLE groups. In a longitudinal analysis of patients with SLE, E-C3d, E-C4d, serum C3, and anti–double-stranded DNA (anti-dsDNA) antibodies were each significantly associated with the SLAM and SELENA–SLEDAI. In a multivariable analysis, E-C4d remained significantly associated with these SLE activity measures after adjusting for serum C3, C4, and anti-dsDNA antibodies; however, E-C3d was associated with the SLAM but not with the SELENA–SLEDAI. Conclusion Determining the levels of the erythrocyte-bound complement activation products, especially E-C4d, is an informative measure of SLE disease activity as compared with assessing serum C4 levels and should be considered for monitoring disease activity in patients with SLE. PMID:20187154

  16. Activities of daily living and manual hand dexterity in persons with idiopathic parkinson disease

    PubMed Central

    Choi, Yoo-Im; Song, Chiang-Soon; Chun, Byung-Yoon

    2017-01-01

    [Purpose] The purpose of this study was to evaluate the relationship between daily activities and manual dexterity in persons with Parkinson disease. [Subjects and Methods] The study participants were 25 patients with idiopathic Parkinson disease. This study used two clinical tools, the box-and-block test and Schwab and England Activities of Daily Living scale, to investigate the relationship between manual dexterity and Schwab and England Activities of Daily Living score. [Results] A positive correlation was observed between the Schwab and England Activities of Daily Living and the box-and-block test scores on the more and less affected sides. Moreover, the Schwab and England Activities of Daily Living score had a greater correlation with the box-and-block test score on the less affected side than that on the more affected side. [Conclusion] Manual dexterity and activities of daily living showed a positive correlation in individuals with Parkinson disease. The results of this study suggest that manual dexterity is an important factor for predicting physical performance in daily living in persons with Parkinson disease. PMID:28356630

  17. Many disease-associated variants of hTERT retain high telomerase enzymatic activity

    PubMed Central

    Zaug, Arthur J.; Crary, Sharon M.; Jesse Fioravanti, Matthew; Campbell, Kristina; Cech, Thomas R.

    2013-01-01

    Mutations in the gene for telomerase reverse transcriptase (hTERT) are associated with diseases including dyskeratosis congenita, aplastic anemia, pulmonary fibrosis and cancer. Understanding the molecular basis of these telomerase-associated diseases requires dependable quantitative measurements of telomerase enzyme activity. Furthermore, recent findings that the human POT1-TPP1 chromosome end-binding protein complex stimulates telomerase activity and processivity provide incentive for testing variant telomerases in the presence of these factors. In the present work, we compare multiple disease-associated hTERT variants reconstituted with the RNA subunit hTR in two systems (rabbit reticulocyte lysates and human cell lines) with respect to telomerase enzymatic activity, processivity and activation by telomere proteins. Surprisingly, many of the previously reported disease-associated hTERT alleles give near-normal telomerase enzyme activity. It is possible that a small deficit in telomerase activity is sufficient to cause telomere shortening over many years. Alternatively, mutations may perturb functions such as the recruitment of telomerase to telomeres, which are essential in vivo but not revealed by simple enzyme assays. PMID:23901009

  18. Activities of daily living and manual hand dexterity in persons with idiopathic parkinson disease.

    PubMed

    Choi, Yoo-Im; Song, Chiang-Soon; Chun, Byung-Yoon

    2017-03-01

    [Purpose] The purpose of this study was to evaluate the relationship between daily activities and manual dexterity in persons with Parkinson disease. [Subjects and Methods] The study participants were 25 patients with idiopathic Parkinson disease. This study used two clinical tools, the box-and-block test and Schwab and England Activities of Daily Living scale, to investigate the relationship between manual dexterity and Schwab and England Activities of Daily Living score. [Results] A positive correlation was observed between the Schwab and England Activities of Daily Living and the box-and-block test scores on the more and less affected sides. Moreover, the Schwab and England Activities of Daily Living score had a greater correlation with the box-and-block test score on the less affected side than that on the more affected side. [Conclusion] Manual dexterity and activities of daily living showed a positive correlation in individuals with Parkinson disease. The results of this study suggest that manual dexterity is an important factor for predicting physical performance in daily living in persons with Parkinson disease.

  19. Inverse associations of outdoor activity and vitamin D intake with the risk of Parkinson's disease.

    PubMed

    Zhu, Dan; Liu, Gui-you; Lv, Zheng; Wen, Shi-rong; Bi, Sheng; Wang, Wei-zhi

    2014-10-01

    Early studies had suggested that vitamin D intake was inversely associated with neurodegenerative diseases, such as Alzheimer's disease and multiple sclerosis. However, the associations of vitamin D intake and outdoor activities with Parkinson's disease (PD) are still unclear, so this study is to evaluate these relationships from a case-control study in elderly Chinese. The study population involved 209 cases with new onsets of PD and 210 controls without neurodegenerative diseases. The data on dietary vitamin D and outdoor activities were collected using a food-frequency questionnaire and self-report questionnaire. Multivariable logistic regressions were used to examine the associations between dietary outdoor activities, vitamin D intake and PD. Adjustment was made for sex, age, smoking, alcohol use, education, and body mass index (BMI). Adjusted odds ratios (ORs) for PD in quartiles for outdoor physical activity were 1 (reference), 0.739 (0.413, 1.321), 0.501 (0.282, 0.891), and 0.437 (0.241, 0.795), respectively (P=0.002 for trend). Adjusted ORs for PD in quartiles for total vitamin D intake were 1 (reference), 0.647 (0.357, 1.170), 0.571 (0.318, 1.022), and 0.538 (0.301, 0.960), respectively (P=0.011 for trend). Our study suggested that outdoor activity and total vitamin D intake were inversely associated with PD, and outdoor activity seems to be more significantly associated with decreased risk for PD.

  20. Complement activity is associated with disease severity in multifocal motor neuropathy

    PubMed Central

    Vlam, Lotte; Cats, Elisabeth A.; Harschnitz, Oliver; Jansen, Marc D.; Piepers, Sanne; Veldink, Jan Herman; Franssen, Hessel; Stork, Abraham C.J.; Heezius, Erik; Rooijakkers, Suzan H.M.; Herpers, Bjorn L.; van Strijp, Jos A.; van den Berg, Leonard H.

    2015-01-01

    Objective: To investigate whether high innate activity of the classical and lectin pathways of complement is associated with multifocal motor neuropathy (MMN) and whether levels of innate complement activity or the potential of anti-GM1 antibodies to activate the complement system correlate with disease severity. Methods: We performed a case-control study including 79 patients with MMN and 79 matched healthy controls. Muscle weakness was documented with Medical Research Council scale sum score and axonal loss with nerve conduction studies. Activity of the classical and lectin pathways of complement was assessed by ELISA. We also determined serum mannose-binding lectin (MBL) concentrations and polymorphisms in the MBL gene (MBL2) and quantified complement-activating properties of anti-GM1 IgM antibodies by ELISA. Results: Activity of the classical and lectin pathways, MBL2 genotypes, and serum MBL concentrations did not differ between patients and controls. Complement activation by anti-GM1 IgM antibodies was exclusively mediated through the classical pathway and correlated with antibody titers (p < 0.001). Logistic regression analysis showed that both high innate activity of the classical pathway of complement and high complement-activating capacity of anti-GM1 IgM antibodies were significantly associated with more severe muscle weakness and axonal loss. Conclusion: High innate activity of the classical pathway of complement and efficient complement-activating properties of anti-GM1 IgM antibodies are determinants of disease severity in patients with MMN. These findings underline the importance of anti-GM1 antibody–mediated complement activation in the pathogenesis and clinical course of MMN. PMID:26161430

  1. Physical Activity And Risk Of End Stage Kidney Disease In The Singapore Chinese Health Study

    PubMed Central

    Jafar, Tazeen Hasan; Jin, Aizhen; Koh, Woon-Puay; Yuan, Jian-Min; Chow, Khuan Yew

    2015-01-01

    Background Physical inactivity is a modifiable risk factor for cardiovascular disease. However, the relationship between physical activity and risk of end-stage kidney disease (ESKD) is not clear. Methods We analyzed data on a prospective cohort of 59,552 Chinese adults aged 45-74 years enrolled in the Singapore Chinese Health Study. Information on physical activity was collected with a structured questionnaire. Physically active individuals were defined as those who engaged in any moderate activities for 2 hours or more per week, and any strenuous activities 30 minutes or more per week. Incident ESKD was identified via record linkage with the Singapore Registry of Birth and Death and Singapore Renal Registry. Cox proportional hazards regression method was used for analysis for risk of incident ESKD alone or ESKD plus death associated with physical activity. Multivariable models were used to account for the potential confounding effect of sociodemographic, life style factors, and known co-morbidites on the physical activity-ESKD risk association. Results During a median follow-up of 15.3 years, a total of 642 incident ESKD occurred, and 9808 study participants died. A 24% lower adjusted risk of ESKD [hazard ratio (HR): 0.76; 95% confidence interval (CI): 0.62-0.93] was associated with moderate or strenuous physical activities compared to no regular physical activity. This association appeared to be dose dependent with the lowest risk for subjects at highest intensity of physical activity (p trend <0.003). Similar results were observed for risk of ESKD plus death. Conclusions Higher levels of physical activity are associated with lower risk of ESKD. Our findings highlight the role of physical activity for prevention of ESKD, which deserves further evaluation in intervention trials. PMID:25346108

  2. Development of an activity disease score in patients with uveitis (UVEDAI).

    PubMed

    Pato, Esperanza; Martin-Martinez, Mª Auxiliadora; Castelló, Adela; Méndez-Fernandez, Rosalía; Muñoz-Fernández, Santiago; Cordero-Coma, Miguel; Martinez-Costa, Lucia; Valls, Elia; Reyes, Miguel; Francisco, Félix; Esteban, Mar; Fonollosa, Alex; Sanchez-Alonso, Fernando; Fernández-Espartero, Cruz; Diaz-Valle, Teresa; Carrasco, José Miguel; Beltran-Catalán, Emma; Hernández-Garfella, Marisa; Hernández, María Victoria; Pelegrin, Laura; Blanco, Ricardo; Diaz-Valle, David

    2017-04-01

    To develop a disease activity index for patients with uveitis (UVEDAI) encompassing the relevant domains of disease activity considered important among experts in this field. The steps for designing UVEDAI were: (a) Defining the construct and establishing the domains through a formal judgment of experts, (b) A two-round Delphi study with a panel of 15 experts to determine the relevant items, (c) Selection of items: A logistic regression model was developed that set ocular inflammatory activity as the dependent variable. The construct "uveitis inflammatory activity" was defined as any intraocular inflammation that included external structures (cornea) in addition to uvea. Seven domains and 15 items were identified: best-corrected visual acuity, inflammation of the anterior chamber (anterior chamber cells, hypopyon, the presence of fibrin, active posterior keratic precipitates and iris nodules), intraocular pressure, inflammation of the vitreous cavity (vitreous haze, snowballs and snowbanks), central macular edema, inflammation of the posterior pole (the presence and number of choroidal/retinal lesions, vascular inflammation and papillitis), and global assessment from both (patient and physician). From all the variables studied in the multivariate model, anterior chamber cell grade, vitreous haze, central macular edema, inflammatory vessel sheathing, papillitis, choroidal/retinal lesions and patient evaluation were included in UVEDAI. UVEDAI is an index designed to assess the global ocular inflammatory activity in patients with uveitis. It might prove worthwhile to motorize the activity of this extraarticular manifestation of some rheumatic diseases.

  3. 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.

  4. Activation of farnesoid X receptor attenuates hepatic injury in a murine model of alcoholic liver disease

    SciTech Connect

    Wu, Weibin; Zhu, Bo; Peng, Xiaomin; Zhou, Meiling; Jia, Dongwei; Gu, Jianxin

    2014-01-03

    Highlights: •FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. •Activation of FXR attenuated alcohol-induced liver injury and steatosis. •Activation of FXR attenuated cholestasis and oxidative stress in mouse liver. -- Abstract: Alcoholic liver disease (ALD) is a common cause of advanced liver disease, and considered as a major risk factor of morbidity and mortality worldwide. Hepatic cholestasis is a pathophysiological feature observed in all stages of ALD. The farnesoid X receptor (FXR) is a member of the nuclear hormone receptor superfamily, and plays an essential role in the regulation of bile acid, lipid and glucose homeostasis. However, the role of FXR in the pathogenesis and progression of ALD remains largely unknown. Mice were fed Lieber-DeCarli ethanol diet or an isocaloric control diet. We used a specific agonist of FXR WAY-362450 to study the effect of pharmacological activation of FXR in alcoholic liver disease. In this study, we demonstrated that FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. Activation of FXR by specific agonist WAY-362450 protected mice from the development of ALD. We also found that WAY-362450 treatment rescued FXR activity, suppressed ethanol-induced Cyp2e1 up-regulation and attenuated oxidative stress in liver. Our results highlight a key role of FXR in the modulation of ALD development, and propose specific FXR agonists for the treatment of ALD patients.

  5. Fibromyalgia in patients with axial spondyloarthritis: epidemiological profile and effect on measures of disease activity.

    PubMed

    Salaffi, Fausto; De Angelis, Rossella; Carotti, Marina; Gutierrez, Marwin; Sarzi-Puttini, Piercarlo; Atzeni, Fabiola

    2014-08-01

    To determine the prevalence of fibromyalgia (FM) in patients with ankylosing spondylitis (AS) or psoriatic arthritis (PsA) characterized by axial involvement (axial-PsA), and to assess the discriminative ability of different versions of the Ankylosing Spondylitis Disease Activity Score (ASDAS) and the Bath Ankylosing Spondylitis Activity Disease Activity Index (BASDAI) in measuring disease activity in three different cohorts of patients with axial spondyloarthritis (axial-SpA), FM, or both (axial-SpA + FM), this study was divided into two phases: (1) 402 patients with definite AS or axial-PsA were examined to diagnose FM and estimate its prevalence; and (2) 419 patients (111 with axial-SpA, 248 with FM, and 60 with aSpA + FM) were evaluated using the different versions of the ASDAS and BASDAI to assess the effect on disease activity. The overall prevalence of FM in the axial-SpA population was 14.9 %, significantly higher among women (p < 0.0001); the estimated prevalence in AS was 12.7 % and in axial-PsA was 17.2 %. Although the BASDAI scores correlated with those of ASDAS-C-reactive protein (CRP) and ASDAS-erythrocyte sedimentation rate (ESR) (p < 0.0001), only ASDAS had sufficient discriminatory ability to assess disease activity. The addition of only one marker of inflammation led to an adequate level of significance (ASDAS-CRP, p = 0.0018; ASDAS-ESR, p = 0.003). FM is common in axial-SpA and more prevalent in female patients. Our findings suggest that ASDAS is better than BASDAI in distinguishing patients with disease activity from those with functional impairment. The use of ASDAS may be very useful in clinical practice as it allows treating patients with the most appropriate therapy.

  6. Heat Shock Protein-70 Expression in Vitiligo and its Relation to the Disease Activity

    PubMed Central

    Doss, Reham William; El-Rifaie, Abdel-Aziz A; Abdel-Wahab, Amr M; Gohary, Yasser M; Rashed, Laila A

    2016-01-01

    Background: Vitiligo is a progressive depigmenting disorder characterized by the loss of functional melanocytes from the epidermis. The etiopathogenesis of vitiligo is still unclear. Heat shock proteins (HSPs) are prime candidates to connect stress to the skin. HSPs were found to be implicated in autoimmune diseases such as rheumatoid arthritis and other skin disorders as psoriasis. Aim and Objectives: The aim of this study was to map the level of HSP-70 in vitiligo lesions to declare its role in the pathogenesis and activity of vitiligo. Materials and Methods: The study included thirty patients with vitiligo and 30 age- and sex-matched healthy controls. Vitiligo patients were divided as regards to the disease activity into highly active, moderately active, and inactive vitiligo groups. Skin biopsies were taken from the lesional and nonlesional skin of patients and from the normal skin of the controls. HSP-70 messenger RNA (mRNA) expression was estimated using quantitative real-time polymerase chain reaction. Results: Our analysis revealed a significantly higher expression of HSP-70 mRNA in lesional skin biopsies from vitiligo patients compared to nonlesional skin biopsies from vitiligo patients (P < 0.001) and compared to skin biopsies from healthy controls (P < 0.001). The level of HSP-70 was not found to be correlated with age, sex, or disease duration. The expression of HSP-70 was correlated with the disease activity and patients with active vitiligo showed higher mean HSP-70 level compared to those with inactive disease. Conclusions: HSP-70 plays a role in the pathogenesis of vitiligo and may enhance the immune response in active disease. PMID:27512186

  7. Stress-Activated Cap’n’collar Transcription Factors in Aging and Human Disease

    PubMed Central

    Sykiotis, Gerasimos P.; Bohmann, Dirk

    2010-01-01

    Cap’n’collar (Cnc) transcription factors are conserved in metazoans and have important developmental and homeostatic functions. The vertebrate Nrf1, Nrf2, and Nrf3, the Caenorhabditis elegans SKN-1, and the Drosophila CncC comprise a subgroup of Cnc factors that mediate adaptive responses to cellular stress. The most studied stress-activated Cnc factor is Nrf2, which orchestrates the transcriptional response of cells to oxidative stressors and electrophilic xenobiotics. In rodent models, signaling by Nrf2 defends against oxidative stress and aging-associated disorders, such as neurodegeneration, respiratory diseases, and cancer. In humans, polymorphisms that decrease Nrf2 abundance have been associated with various pathologies of the skin, respiratory system, and digestive tract. In addition to preventing disease in rodents and humans, Cnc factors have lifespan-extending and anti-aging functions in invertebrates. However, despite the pro-longevity and antioxidant roles of stress-activated Cnc factors, their activity paradoxically declines in aging model organisms and in humans suffering from progressing respiratory disease or neurodegeneration. We review the roles and regulation of stress-activated Cnc factors across species, present all reported instances in which their activity is paradoxically decreased in aging and disease, and discuss the possibility that the pharmacological restoration of Nrf2 signaling may be useful in the prevention and treatment of age-related diseases. PMID:20215646

  8. Sexual function in Moroccan women with rheumatoid arthritis and its relationship with disease activity.

    PubMed

    Hari, Asmae; Rostom, Samira; Lahlou, Racha; Bahiri, Rachid; Hajjaj-Hassouni, Najia

    2015-06-01

    The objective of this study was to evaluate sexual function in women with rheumatoid arthritis (RA) using an auto-questionnaire Female Sexual Function Index (FSFI) and study its correlation with disease activity. Sixty patients with RA and 40 healthy controls were included in this exploratory study. Sociodemographic, clinical, and laboratory characteristics were assessed. The disease activity was assessed by auto-questionnaires Routine Assessment of Patient Index Data 3 (RAPID3) and Rheumatoid Arthritis Disease Activity Index 5 (RADAI5) judged by 28 DAS ESR. Sexual function was assessed by an auto-questionnaire specific for female sexuality: FSFI during the last 4 weeks. The definition of sexual dysfunction was considered by FSFI score less than or equal to 26.5. The mean age of RA patients and controls was 45.95 ± 9.3 and 45.01 ± 9.2, respectively. According to FSFI, the percentage of FSD in women with RA was significantly higher than that in the control group. All dimensions of sexuality were affected (desire, arousal, lubrication, orgasm, and satisfaction) except pain. The multivariate linear regression analysis indicated that the swollen joints and the RADAI5 were the independent variables of disease activity associated with sexual dysfunction in women with RA. This study suggests that sexual dysfunction among women suffering from rheumatoid arthritis is found when a targeted questionnaire is used to identify it and that the increased disease activity has a negative effect of sexual function.

  9. Vectra DA for the objective measurement of disease activity in patients with rheumatoid arthritis.

    PubMed

    Segurado, O G; Sasso, E H

    2014-01-01

    Quantitative and regular assessment of disease activity in rheumatoid arthritis (RA) is required to achieve treatment targets such as remission and to optimize clinical outcomes. To assess inflammation accurately, predict joint damage and monitor treatment response, a measure of disease activity in RA should reflect the pathological processes resulting in irreversible joint damage and functional disability. The Vectra DA blood test is an objective measure of disease activity for patients with RA. Vectra DA provides an accurate, reproducible score on a scale of 1 to 100 based on the concentrations of 12 biomarkers that reflect the pathophysiologic diversity of RA. The analytical validity, clinical validity, and clinical utility of Vectra DA have been evaluated for patients with RA in registries and prospective and retrospective clinical studies. As a biomarker-based instrument for assessing disease activity in RA, the Vectra DA test can help monitor therapeutic response to methotrexate and biologic agents and assess clinically challenging situations, such as when clinical measures are confounded by non-inflammatory pain from fibromyalgia. Vectra DA scores correlate with imaging of joint inflammation and are predictive for radiographic progression, with high Vectra DA scores being associated with more frequent and severe progression and low scores being predictive for non-progression. In summary, the Vectra DA score is an objective measure of RA disease activity that quantifies inflammatory status. By predicting risk for joint damage more effectively than conventional clinical and laboratory measures, it has the potential to complement these measures and optimise clinical decision making.

  10. The relation of hand functions with radiological damage and disease activity in rheumatoid arthritis.

    PubMed

    Birtane, Murat; Kabayel, Derya Demirbag; Uzunca, Kaan; Unlu, Ercument; Tastekin, Nurettin

    2008-03-01

    The purpose of this study was to investigate specifically the correlation of hand functions determined by Duruoz hand index (DHI) with radiological findings and disease activity in rheumatoid arthritis (RA) patients. Forty-eight RA patients were evaluated with DHI questionnaire, disease activity score (DAS) 28 and modified Larsen scoring method. Correlation between DAS-28 and DHI was assessed in all the patients. Mean DHI scores were compared between patients in remission (DAS-28 < 2.6) and patients who have more or less disease activity (DAS-28 >or= 2.6). To exclude the probable conflicting effect of disease activity on hand functions, the correlation between radiological scores and DHI was investigated only in patients with remission. There was a positive correlation between DAS-28 and DHI in all patients group (r = 0.434, P < 0.002). No correlation between the radiological scores of any joint groups and DHI could be found in patients with remission. Hand functions seemed to be affected prominently from disease activity. Radiological scores demonstrating joint damage were not in relation with hand functions.

  11. Evaluating disease activity in patients with ankylosing spondylitis and rheumatoid arthritis using 99mtc-glucosamine

    PubMed Central

    Manolios, Nicholas; Ali, Marina; Camden, Bradley; Aflaky, Elham; Pavic, Katrina; Markewycz, Andrew; De Costa, Robert; Angelides, Socrates

    2016-01-01

    Objective To evaluate the clinical utility of a novel radiotracer, 99mTc-glucosamine, in assessing disease activity of both rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Material and Methods: Twenty-five patients with RA (nine males and 16 females) and 12 patients with AS (all male) at various stages of disease were recruited for the study. A clinical history and examination was performed, followed by the measurement of hematological, biochemical, and autoimmune serological parameters to assess disease activity. 99mTc-glucosamine was intravenously administered and scans were compared with other imaging modalities, including plain X-ray, magnetic resonance imaging (MRI), and bone scans. Results In patients with AS, 99mTc-glucosamine scans were more capable of identifying active disease and differentiating between inflammatory and non-inflammatory causes. In patients with RA, 99mTc-glucosamine accumulated at all known sites of disease involvement. Uptake was most pronounced in patients with active untreated disease. The relative tracer activity in the involved joints increased with time compared with that in the adjoining soft tissue, liver, and cardiac blood pool. Using Spearman’s correlation coefficient, there was a positive correlation among glucosamine scan scores, C-reactive protein (p=0.048), and clinical assessment (p=0.003), which was not noted with bone scans. Conclusion The radiotracer was well tolerated by all patients, with no adverse reactions. 99mTc-glucosamine imaging could detect spinal inflammation in AS. With respect to RA, 99mTc-glucosamine was a viable alternative to 99mTc-labeled methylene diphosphonate nuclear bone scans for imaging inflamed joints and had the added advantage of demonstrating a significant clinical correlation between disease activity and scan findings. PMID:27708974

  12. BACE1 and BACE2 Enzymatic Activities in Alzheimer’s Disease

    PubMed Central

    Ahmed, Rachel R.; Holler, Christopher J.; Webb, Robin L.; Li, Feng; Beckett, Tina L.; Murphy, M. Paul

    2009-01-01

    β-Secretase is the rate limiting enzymatic activity in the production of the amyloid-β peptide (Aβ) and is thought to be involved in Alzheimer’s disease (AD) pathogenesis. Although BACE1 (β-site APP Cleaving Enzyme 1, EC 3.4.23.46) has received significant attention, the related BACE2 (EC 3.4.23.45) has not. Though BACE2 is also expressed in the brain, its potential role in AD has not been resolved. In this study, we compared the activities of both BACE1 and BACE2, which were isolated from the same samples of frontal cortex from both AD-affected individuals and age-matched controls. BACE1 activity showed a significant positive correlation with the amount of extractable Aβ, and BACE1 protein and activity were significantly increased in AD cases. Unexpectedly, there were substantial total amounts of BACE2 protein and enzymatic activity in the human brain. BACE2 activity did not change significantly in the AD brain, and was not related to Aβ concentration. These data indicate that BACE1 likely accounts for most of the Aβ produced in the human brain, and that BACE2 activity is not a likely contributor. However, since both forms of BACE compete for the same substrate pool, even small changes in BACE2 activity could have consequences for human disease. PMID:19968762

  13. Disease activity in systemic lupus erythematosus patients with end-stage renal disease: systematic review of the literature.

    PubMed

    Mattos, Patrícia; Santiago, Mittermayer B

    2012-06-01

    It is not unusual that patients with systemic lupus erythematosus (SLE) progress to terminal renal failure and subsequently require renal replacement therapy. Previous studies have shown that clinical and/or serological remission in patients with SLE is common in those who develop end-stage renal disease (ESRD). On the other hand, the persistence of lupus activity among patients undergoing long-term dialysis is not rare, either. The aim of this study is to define, by means of a systematic review, the course of SLE activity in patients who developed ESRD. Data were obtained through searches for articles in the MEDLINE (1966 to 2011), SCielo, and LILACS databases, using the following keywords: "chronic renal failure", "systemic lupus erythematosus", "end-stage renal disease", "lupus activity", "disease activity", "lupus flare", "hemodialysis", and "renal replacement therapy" and their corresponding translations in Portuguese. Twenty-four articles were found which evaluated the degree of lupus activity in patients with ESRD. Fifteen of these studies spoke of a substantial reduction of clinical and/or serological activity after the development of ESRD, while nine articles found that the amount of clinical and/or serological activity was similar to that of the phase prior to terminal renal failure, or it occurred in at least 50% of the patients studied. Although the majority of studies showed that lupus flares tend to decrease in frequency in patients who develop ESRD, in this scenario, one should be prepared to correctly diagnose a recurrence of the disease, as well as to perform appropriate therapy.

  14. Tau-based therapeutics for Alzheimer's disease: active and passive immunotherapy.

    PubMed

    Panza, Francesco; Solfrizzi, Vincenzo; Seripa, Davide; Imbimbo, Bruno P; Lozupone, Madia; Santamato, Andrea; Tortelli, Rosanna; Galizia, Ilaria; Prete, Camilla; Daniele, Antonio; Pilotto, Alberto; Greco, Antonio; Logroscino, Giancarlo

    2016-09-01

    Pharmacological manipulation of tau protein in Alzheimer's disease included microtubule-stabilizing agents, tau protein kinase inhibitors, tau aggregation inhibitors, active and passive immunotherapies and, more recently, inhibitors of tau acetylation. Animal studies have shown that both active and passive approaches can remove tau pathology and, in some cases, improve cognitive function. Two active vaccines targeting either nonphosphorylated (AAD-vac1) and phosphorylated tau (ACI-35) have entered Phase I testing. Notwithstanding, the recent discontinuation of the monoclonal antibody RG7345 for Alzheimer's disease, two other antitau antibodies, BMS-986168 and C2N-8E12, are also currently in Phase I testing for progressive supranuclear palsy. After the recent impressive results in animal studies obtained by salsalate, the dimer of salicylic acid, inhibitors of tau acetylation are being actively pursued.

  15. Psychosocial stress and cardiovascular disease risk: the role of physical activity.

    PubMed

    Hamer, Mark

    2012-01-01

    Chronic stress and depression are associated with increased risk of cardiovascular disease and poorer prognosis, and physical (in)activity may be a key underlying biobehavioral mechanism. Physical activity has antidepressant effects, and physically fitter, more active individuals seem to be more biologically resilient to psychosocial stressors. This article will present data from a series of population cohort studies and laboratory-based psychophysiological studies to explore the role of physical activity as a protective factor against the effects of psychosocial stress on cardiovascular disease. These mechanisms may improve the treatment and prevention of stress-related illnesses and, thus, has important implications for public health and clinical care of high-risk patients.

  16. Understanding the impact of deep brain stimulation on ambulatory activity in advanced Parkinson's disease.

    PubMed

    Rochester, Lynn; Chastin, Sebastien Francois Martin; Lord, Sue; Baker, Katherine; Burn, David John

    2012-06-01

    Whilst deep brain stimulation of the subthalamic nucleus (DBS-STN) improves the motor symptoms of Parkinson's disease (PD), its effect on daily activity is unknown. We aimed to quantify changes in ambulatory activity following DBS-STN in advanced PD using novel accelerometry based measures that describe changes to the volume and pattern of walking. Seventeen participants with advanced PD were measured over a 7-day period using an activPAL (™) activity monitor. Data were collected 6 weeks before and 6 months after surgery and included measures that describe the volume and pattern of ambulatory activity (number of steps per day, accumulation, diversity and variability of walking time), alongside standard measures for disease severity, freezing of gait, gait speed, and extended activities of daily living. Activity outcomes were compared pre- and 6 months post-surgery using linear mixed models and correlated with standard outcomes. The results of this study are despite significant improvements in motor symptoms after surgery, the volume of ambulatory activity (total number of steps per day) did not change (P = 0.468). However, significant increases in length and variability of walking bouts emerged, suggesting improvements in diversity and flexibility of walking patterns. Motor severity and extended activities of daily living scores were significantly correlated with walking bout variability but not with volume of walking. Thus, the conclusions are reduction in motor symptom severity after DBS-STN translated into selective improvements in daily activity. Novel measures derived from accelerometry provide a discrete measure of performance and allow closer interpretation of the impact of DBS-STN on real-world activity.

  17. Mast cell activation disease: a concise practical guide for diagnostic workup and therapeutic options

    PubMed Central

    2011-01-01

    Mast cell activation disease comprises disorders characterized by accumulation of genetically altered mast cells and/or abnormal release of these cells' mediators, affecting functions in potentially every organ system, often without causing abnormalities in routine laboratory or radiologic testing. In most cases of mast cell activation disease, diagnosis is possible by relatively non-invasive investigation. Effective therapy often consists simply of antihistamines and mast cell membrane-stabilising compounds supplemented with medications targeted at specific symptoms and complications. Mast cell activation disease is now appreciated to likely be considerably prevalent and thus should be considered routinely in the differential diagnosis of patients with chronic multisystem polymorbidity or patients in whom a definitively diagnosed major illness does not well account for the entirety of the patient's presentation. PMID:21418662

  18. Epidemic spreading of interacting diseases with activity of nodes reshapes the critical threshold

    NASA Astrophysics Data System (ADS)

    Fan, Chongjun; Jin, Yang; Huo, Liang-An; Liu, Chen; Yang, Yunpeng

    In this paper, based on susceptible-infected-susceptible (SIS) scheme, we introduce a framework that allows us to describe the spreading dynamics of two interacting diseases with active nodes. Different from previous studies, the two different diseases, propagating concurrently on the same population, can interact with each other by modifying their transmission rates. Meanwhile, according to certain probabilities, each node on the complex networks rotates between active state and inactive state. Based on heterogeneous mean-field approach, we analyze the epidemic thresholds of the two diseases and compute the temporal evolution characterizing the spreading dynamics. In addition, we validate these theoretical predictions by numerical simulations with phase diagrams. Results show that the secondary thresholds for the two opposite scenarios (mutual enhancement scenario and mutual impairment scenario) are different. We also find that the value of critical threshold and the final size of spreading dynamics are reduced as the node activity rate decreases.

  19. Development and First Validation of a Disease Activity Score for Gout

    PubMed Central

    Carrara, Greta; Viroli, Cinzia; Cimmino, Marco A.; Taylor, William J.; Manara, Maria; Govoni, Marcello; Salaffi, Fausto; Punzi, Leonardo; Montecucco, Carlomaurizio; Matucci‐Cerinic, Marco; Minisola, Giovanni; Ariani, Alarico; Galossi, Alessandra; Lauriti, Ciro; Fracassi, Elena; Idolazzi, Luca; Bardelli, Marco; Selvi, Enrico; Tirri, Enrico; Furini, Federica; Inverardi, Flora; Calabrò, Andrea; Porta, Francesco; Bittelli, Raffaele; Venturino, Francesco; Capsoni, Franco; Prevete, Immacolata; Sebastiani, Giandomenico; Selmi, Carlo; Fabbriciani, Gianluigi; D'Avola, Giovanni; Botticella, Giulia; Serale, Francesca; Seminara, Giulia; D'Alessandro, Giuseppe; Santo, Leonardo; Longato, Lorena; Zaccara, Eleonora; Sinigaglia, Luigi; Atteritano, Marco; Broggini, Marco; Caprioli, Marta; Favero, Marta; Sallì, Salvatore; Scarati, Marco; Parisi, Simone; Malavolta, Nazzarena; Corvaglia, Stefania; Scarpato, Salvatore; Veneto, Vittorio

    2016-01-01

    Objective To develop a new composite disease activity score for gout and provide its first validation. Methods Disease activity has been defined as the ongoing presence of urate deposits that lead to acute arthritis and joint damage. Every measure for each Outcome Measures in Rheumatology core domain was considered. A 3‐step approach (factor analysis, linear discriminant analysis, and linear regression) was applied to derive the Gout Activity Score (GAS). Decision to change treatment or 6‐month flare count were used as the surrogate criteria of high disease activity. Baseline and 12‐month followup data of 446 patients included in the Kick‐Off of the Italian Network for Gout cohort were used. Construct‐ and criterion‐related validity were tested. External validation on an independent sample is reported. Results Factor analysis identified 5 factors: patient‐reported outcomes, joint examination, flares, tophi, and serum uric acid (sUA). Discriminant function analysis resulted in a correct classification of 79%. Linear regression analysis identified a first candidate GAS including 12‐month flare count, sUA, visual analog scale (VAS) of pain, VAS global activity assessment, swollen and tender joint counts, and a cumulative measure of tophi. Alternative scores were also developed. The developed GAS demonstrated a good correlation with functional disability (criterion validity) and discrimination between patient‐ and physician‐reported measures of active disease (construct validity). The results were reproduced in the external sample. Conclusion This study developed and validated a composite measure of disease activity in gout. Further testing is required to confirm its generalizability, responsiveness, and usefulness in assisting with clinical decisions. PMID:26815286

  20. A New Therapeutic Strategy for Autosomal Dominant Polycystic Kidney Disease: Activation of AMP Kinase by Metformin

    DTIC Science & Technology

    2012-07-01

    magnitude, [32]), indicating that urine succinate levels could be a potential biomarker for detecting diabetic nephropathy early on in the disease progression...a drug in wide clinical use for both non-insulin dependent diabetes mellitus and Polycystic Ovary Syndrome, stimulates AMPK (10, 11). We therefore...regimens can produce AMPK activation in wild type mice. In addition, we will determine whether activation of AMPK by metformin treatment exhibits any

  1. Behçet's disease diagnosed after acute HIV infection: viral replication activating underlying autoimmunity?

    PubMed

    Roscoe, Clay; Kinney, Rebecca; Gilles, Ryan; Blue, Sky

    2015-05-01

    Behçet's disease is an autoimmune systemic vasculitis that can occur after exposure to infectious agents. Behçet's disease also has been associated with HIV infection, including de novo development of this condition during chronic HIV infection and resolution of Behçet's disease symptoms following initiation of antiretroviral therapy. We describe a patient who presented with systemic vasculitis with skin and mucous membrane ulcerations in the setting of acute HIV infection, who was eventually diagnosed with Behçet's disease, demonstrating a possible link between acute HIV infection, immune activation and development of autoimmunity.

  2. Vitamin D deficiency in rheumatoid arthritis: prevalence, determinants and associations with disease activity and disability

    PubMed Central

    2010-01-01

    Introduction The aim of this study was to estimate the prevalence and determinants of vitamin D deficiency in patients with rheumatoid arthritis (RA) as compared to healthy controls and to analyze the association between 25-hydroxyvitamin D (25(OH)D) with disease activity and disability. Methods The study includes 1,191 consecutive RA patients (85% women) and 1,019 controls, not on vitamin D supplements, from 22 Italian rheumatology centres. Together with parameters of disease activity, functional impairment, and mean sun exposure time, all patients had serum 25(OH)D measured in a centralized laboratory. Results A total of 55% of RA patients were not taking vitamin D supplements; the proportion of these with vitamin D deficiency (25(OH)D level <20 ng/ml) was 52%. This proportion was similar to that observed in control subjects (58.7%). One third of supplemented patients were still vitamin D deficient. In non-supplemented RA patients 25(OH)D levels were negatively correlated with the Health Assessment Questionnaire Disability Index, Disease Activity Score (DAS28), and Mobility Activities of daily living score. Significantly lower 25(OH)D values were found in patients not in disease remission or responding poorly to treatment, and with the highest Steinbrocker functional state. Body mass index (BMI) and sun exposure time were good predictors of 25(OH)D values (P < 0.001). The association between disease activity or functional scores and 25(OH)D levels remained statistically significant even after adjusting 25(OH)D levels for both BMI and sun exposure time. Conclusions In RA patients vitamin D deficiency is quite common, but similar to that found in control subjects; disease activity and disability scores are inversely related to 25(OH)D levels. PMID:21114806

  3. Cell associated urokinase activity and colonic epithelial cells in health and disease.

    PubMed Central

    Gibson, P R; van de Pol, E; Doe, W F

    1991-01-01

    It is not known if urokinase-type plasminogen activator (uPA) is associated with normal colonic epithelial cells. The aims of this study were to determine if normal colonic epithelial cells have uPA activity and whether this is concentrated at the cell membrane. In addition, the contribution of colonic epithelial cell associated uPA activity to disease related pertubations of mucosal uPA activity were examined. A highly enriched population of colonic epithelial cells was isolated from resected colon or biopsy specimens by an enzymatic technique. uPA activity was measured in cell homogenates by a specific and sensitive colorimetric method and expressed relative to cellular DNA. In two experiments subcellular fractionation of colonic epithelial cells was performed by nitrogen cavitation followed by ultracentrifugation over a linear sucrose gradient. The fractions collected were analysed for uPA and organelle-specific enzyme activities. Normal colonic epithelial cells have cell associated uPA activity (mean (SEM) 5.6 (1.1) IU/mg, n = 18). This colocalised with fractions enriched for leucine-beta-naphthylamidase and 5'-nucleotidase, markers of plasma membrane. uPA activities in epithelial cells from cancerous colons (9.8 (3.1) n = 7) or from mucosa affected by inflammatory bowel disease (3.8 (0.7) n = 15) were not significantly different from normal (paired t test), while that in epithelial cells from greatly inflamed mucosa was similar to that from autologous normal or mildly inflamed areas (4.4 (1.2) v 5.9 (3.6), n = 9). Thus normal colonic epithelial cells have cell associated uPA activity which is concentrated on the plasma membranes, suggesting the presence of uPA receptors. Increased mucosal levels of uPA previously reported in patients with inflammatory bowel disease are not due to increased colonic epithelial cell associated uPA. PMID:1650741

  4. Enhanced colonic nitric oxide generation and nitric oxide synthase activity in ulcerative colitis and Crohn's disease.

    PubMed Central

    Rachmilewitz, D; Stamler, J S; Bachwich, D; Karmeli, F; Ackerman, Z; Podolsky, D K

    1995-01-01

    Recent studies have suggested that nitric oxide (NO.), the product of nitric oxide synthase in inflammatory cells, may play a part in tissue injury and inflammation through its oxidative metabolism. In this study the colonic generation of oxides of nitrogen (NOx) and nitric oxide synthase activity was determined in ulcerative colitis and Crohn's disease. Colonic biopsy specimens were obtained from inflammatory bowel disease patients and from normal controls. Mucosal explants were cultured in vitro for 24 hours and NOx generation was determined. Nitric oxide synthase activity was monitored by the conversion of [3H]-L-arginine to citrulline. Median NOx generation by inflamed colonic mucosa of patients with active ulcerative colitis and Crohn's colitis was 4.2- and 8.1-fold respectively higher than that by normal human colonic mucosa. In ulcerative colitis and Crohn's colitis nitric oxide synthase activity was 10.0- and 3.8-fold respectively higher than in normal subjects. Colonic NOx generation is significantly decreased by methylprednisolone and ketotifen. The decrease in NOx generation by cultured colonic mucosa induced by methylprednisolone suggests that NO synthase activity is induced during the culture and the steroid effect may contribute to its therapeutic effect. Enhanced colonic NOx generation by stimulated nitric oxide synthase activity in ulcerative colitis and Crohn's disease may contribute to tissue injury. PMID:7541008

  5. Impact of physical activity on inflammation: effects on cardiovascular disease risk and other inflammatory conditions

    PubMed Central

    Cicero, Arrigo

    2012-01-01

    Since the 19th century, many studies have enlightened the role of inflammation in atherosclerosis, changing our perception of “vessel plaque due to oxidized lipoproteins”, similar to a “rusted pipe”, towards a disease with involvement of many cell types and cytokines with more complex mechanisms. Although “physical activity” and “physical exercise” are two terms with some differences in meaning, compared to sedentary lifestyle, active people have lower cardiovascular risk and lower inflammatory markers. Activities of skeletal muscle reveal “myokines” which have roles in both the immune system and adipose tissue metabolism. In vitro and ex-vivo studies have shown beneficial effects of exercise on inflammation markers. Meanwhile in clinical studies, some conflicting results suggested that type of activity, exercise duration, body composition, gender, race and age may modulate anti-inflammatory effects of physical exercise. Medical data on patients with inflammatory diseases have shown beneficial effects of exercise on disease activity scores, patient well-being and inflammatory markers. Although the most beneficial type of activity and the most relevant patient group for anti-inflammatory benefits are still not clear, studies in elderly and adult people generally support anti-inflammatory effects of physical activity and moderate exercise could be advised to patients with cardiovascular risk such as patients with metabolic syndrome. PMID:23185187

  6. 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.

  7. Beta 2-adrenergic receptor activation enhances neurogenesis in Alzheimer's disease mice

    PubMed Central

    Chai, Gao-shang; Wang, Yang-yang; Yasheng, Amina; Zhao, Peng

    2016-01-01

    Impaired hippocampal neurogenesis is one of the early pathological features of Alzheimer's disease. Enhancing adult hippocampal neurogenesis has been pursued as a potential therapeutic strategy for Alzheimer's disease. Recent studies have demonstrated that environmental novelty activates β2-adrenergic signaling and prevents the memory impairment induced by amyloid-β oligomers. Here, we hypothesized that β2-adrenoceptor activation would enhance neurogenesis and ameliorate memory deficits in Alzheimer's disease. To test this hypothesis, we investigated the effects and mechanisms of action of β2-adrenoceptor activation on neurogenesis and memory in amyloid precursor protein/presenilin 1 (APP/PS1) mice using the agonist clenbuterol (intraperitoneal injection, 2 mg/kg). We found that β2-adrenoceptor activation enhanced hippocampal neurogenesis, ameliorated memory deficits, and increased dendritic branching and the density of dendritic spines. These effects were associated with the upregulation of postsynaptic density 95, synapsin 1 and synaptophysin in APP/PS1 mice. Furthermore, β2-adrenoceptor activation decreased cerebral amyloid plaques by decreasing APP phosphorylation at Thr668. These findings suggest that β2-adrenoceptor activation enhances neurogenesis and ameliorates memory deficits in APP/PS1 mice. PMID:27904493

  8. Increasing Patient Activation Could Improve Outcomes for Patients with Inflammatory Bowel Disease.

    PubMed

    Shah, Shawn L; Siegel, Corey A

    2015-12-01

    Inflammatory bowel disease (IBD) is a complex disease process that often requires the integration of skills from various health care providers to adequately meet the needs of patients with IBD. The medical and surgical treatment options for IBD have become more complicated and are frequently a source of angst for both the patient and provider. However, it has become more important than ever to engage patients in navigating the treatment algorithm. Although novel in the IBD world, the concept of patients' becoming more active and effective managers of their care has been well studied in other disease processes such as diabetes mellitus and mental illness. This idea of patient activation refers to a patient understanding his or her role in the care process and having the skill sets and self-reliance necessary to manage his or her own health care. Over the past decade, evidence supporting the role of patient activation in chronic illness has grown, revealing improved health outcomes, enhanced patient experiences, and lower overall costs. Patient activation can be measured, and interventions have been shown to improve levels of activation over time and influence outcomes. A focus on patient activation is very appropriate for patients with IBD because this may potentially serve as a tool for IBD providers to not only improve patient outcomes and experience but also reduce health care costs.

  9. Relationship between serum leptin level and disease activity in patients with systemic sclerosis.

    PubMed

    Budulgan, Mahmut; Dilek, Banu; Dağ, Şevin Buluttekin; Batmaz, Ibrahim; Yıldız, İsmail; Sarıyıldız, Mustafa Akif; Çevik, Remzi; Nas, Kemal

    2014-03-01

    To determine the relationship between serum leptin levels and disease activity in systemic sclerosis (SSc). A total of 60 subjects (30 controls and 30 patients) were included. The inflammatory markers and leptin levels were evaluated and body mass index (BMI) was measured for both groups. The assessment of the skin involvement was performed based on the modified Rodnan skin score (mRSS). Disease activity was evaluated according to the Valentini scleroderma disease activity index. There was a significant difference between the patient and control groups in terms of BMI (p < 0.05); however there was no difference with regards to age and gender (p > 0.05). Valentini scores and mRSS were determined to be significantly higher in active patients (n = 14) than in inactive patients (n = 16) (p < 0.05). No significant difference was determined between groups in terms of leptin levels (p > 0.05). However, leptin levels were significantly lower in active patients than in inactive patients (p < 0.05). We found a significant positive correlation between serum leptin and BMI (p < 0.05), and leptin and serum C3 levels (p < 0.05); no relationship was detected between leptin and other parameters. Leptin can be used as an activity marker in SSc. Further studies, including larger series, should be carried out to clarify this relationship.

  10. Fecal calprotectin is associated with disease activity in patients with ankylosing spondylitis.

    PubMed

    Duran, Arzu; Kobak, Senol; Sen, Nazime; Aktakka, Seniha; Atabay, Tennur; Orman, Mehmet

    2016-01-01

    Calprotectin is one of the major antimicrobial S100 leucocyte proteins. Serum calprotectin levels are associated with certain inflammatory diseases such as rheumatoid arthritis, systemic lupus erythematosus and inflammatory bowel disease. The aim of this study was to investigate serum and fecal calprotectin levels in patients with ankylosing spondylitis (AS) and show their potential relations to the clinical findings of the disease. Fifty-one patients fulfilling the New York criteria of AS and 43 healthy age- and gender-matched volunteers were included in the study. Physical and locomotor system examinations were performed and history data were obtained for all patients. Disease activity parameters were assessed together with anthropometric parameters. Routine laboratory examinations and genetic testing (HLA-B27) were performed. Serum calprotectin levels and fecal calprotectin levels were measured by an enzyme-linked immunosorbent assay. The mean age of the patients was 41.5 years, the mean duration of the disease was 8.6 years, and the delay in diagnosis was 4.2 years. Serum calprotectin levels were similar in both AS patients and in the control group (p=0.233). Serum calprotectin level was correlated with Bath AS disease activity index (BASDAI) and Bath AS functional index (BASFI) (p=0.001, p=0.002, respectively). A higher level of fecal calprotectin was detected in AS patients when compared with the control group. A statistically significant correlation between fecal calprotectin level and BASDAI, BASFI, C-reactive protein and Erythrocyte sedimentation rate were detected (p=0.002, p=0.005, p=0.001, p=0.002, respectively). The results indicated that fecal calprotectin levels were associated with AS disease findings and activity parameters. Calprotectin is a vital disease activity biomarker for AS and may have an important role in the pathogenesis of the disease. Multi-centered prospective studies are needed in order to provide further insight.

  11. Endothelial Activation and Repair During Hantavirus Infection: Association with Disease Outcome

    PubMed Central

    Connolly-Andersen, Anne-Marie; Thunberg, Therese; Ahlm, Clas

    2014-01-01

    Background.  Endothelial activation and dysfunction play a central role in the pathogenesis of sepsis and viral hemorrhagic fevers. Hantaviral disease is a viral hemorrhagic fever and is characterized by capillary dysfunction, although the underlying mechanisms for hantaviral disease are not fully elucidated. Methods.  The temporal course of endothelial activation and repair were analyzed during Puumala hantavirus infection and associated with disease outcome and a marker for hypoxia, insulin-like growth factor binding protein 1 (IGFBP-1). The following endothelial activation markers were studied: endothelial glycocalyx degradation (syndecan-1) and leukocyte adhesion molecules (soluble vascular cellular adhesion molecule 1, intercellular adhesion molecule 1, and endothelial selectin). Cytokines associated with vascular repair were also analyzed (vascular endothelial growth factor, erythropoietin, angiopoietin, and stromal cell-derived factor 1). Results.  Most of the markers we studied were highest during the earliest phase of hantaviral disease and associated with clinical and laboratory surrogate markers for disease outcome. In particular, the marker for glycocalyx degradation, syndecan-1, was significantly associated with levels of thrombocytes, albumin, IGFBP-1, decreased blood pressure, and disease severity. Conclusions.  Hantaviral disease outcome was associated with endothelial dysfunction. Consequently, the endothelium warrants further investigation when designing future medical interventions. PMID:25734100

  12. A potential treatment of non-alcoholic fatty liver disease with SIRT1 activators.

    PubMed

    Colak, Yasar; Yesil, Atakan; Mutlu, Hasan Huseyin; Caklili, Ozge Telci; Ulasoglu, Celal; Senates, Ebubekir; Takir, Mumtaz; Kostek, Osman; Yilmaz, Yusuf; Yilmaz Enc, Feruze; Tasan, Guralp; Tuncer, Ilyas

    2014-09-01

    Sirtuins (SIRTs) are members of the silent information regulator-2 family and act as nicotinamide adenine dinucleotide (NAD+)-dependent histone/protein deacetylases. The de-acetylation of proteins and histones results in an up- or down-regulation of gene transcription and protein function. In recent years, the regulatory action of the deacetylation activity of SIRT1 has been shown to have a positive impact on the pathophysiological mechanisms of nonalcoholic fatty liver disease (NAFLD). Among the effects of SIRT1 are: its healing activity on insulin sensitivity, thereby ameliorating glycemic regulation; its mimetic activity on calorie restriction; its antihyperlipidemic activity on lipid homeostasis via the liver, adipose tissues and skeletal muscles; its anti-inflammatory activities; its protective effects against cardiovascular events and endothelial dysfunction; its positive influence on autophagy, apoptosis and cancer; and finally, its anti-aging activity. The current approach for the treatment of NAFLD involves the treatment of etiological factors and recommendation of life-style changes including more physical activity and a low-calorie diet. However, there is no specific medical treatments for NAFLD. The therapeutic potential of SIRT1 activity in the treatment of NAFLD discovered in humans has been presented in this article. In this review, the potential effects of SIRT1 activation on NAFLD-related pathophysiological mechanisms and on the treatment of NAFLD are discussed.

  13. Combined influence of healthy diet and active lifestyle on cardiovascular disease risk factors in adolescents.

    PubMed

    Cuenca-García, M; Ortega, F B; Ruiz, J R; González-Gross, M; Labayen, I; Jago, R; Martínez-Gómez, D; Dallongeville, J; Bel-Serrat, S; Marcos, A; Manios, Y; Breidenassel, C; Widhalm, K; Gottrand, F; Ferrari, M; Kafatos, A; Molnár, D; Moreno, L A; De Henauw, S; Castillo, M J; Sjöström, M

    2014-06-01

    To investigate the combined influence of diet quality and physical activity on cardiovascular disease (CVD) risk factors in adolescents, adolescents (n = 1513; 12.5-17.5 years) participating in the Healthy Lifestyle in Europe by Nutrition in Adolescence study were studied. Dietary intake was registered using a 24-h recall and a diet quality index was calculated. Physical activity was assessed by accelerometry. Lifestyle groups were computed as: healthy diet and active, unhealthy diet but active, healthy diet but inactive, and unhealthy diet and inactive. CVD risk factor measurements included cardiorespiratory fitness, adiposity indicators, blood lipid profile, blood pressure, and insulin resistance. A CVD risk score was computed. The healthy diet and active group had a healthier cardiorespiratory profile, fat mass index (FMI), triglycerides, and high-density lipoprotein cholesterol (HDL-C) levels and total cholesterol (TC)/HDL-C ratio (all P ≤ 0.05). Overall, active adolescents showed higher cardiorespiratory fitness, lower FMI, TC/HDL-C ratio, and homeostasis model assessment index and healthier blood pressure than their inactive peers with either healthy or unhealthy diet (all P ≤ 0.05). Healthy diet and active group had healthier CVD risk score compared with the inactive groups (all P ≤ 0.02). Thus, a combination of healthy diet and active lifestyle is associated with decreased CVD risk in adolescents. Moreover, an active lifestyle may reduce the adverse consequences of an unhealthy diet.

  14. Slowing of oscillatory brain activity is a stable characteristic of Parkinson's disease without dementia.

    PubMed

    Stoffers, D; Bosboom, J L W; Deijen, J B; Wolters, E C; Berendse, H W; Stam, C J

    2007-07-01

    Extensive changes in resting-state oscillatory brain activity have recently been demonstrated using magnetoencephalography (MEG) in moderately advanced, non-demented Parkinson's disease patients relative to age-matched controls. The aim of the present study was to determine the onset and evolution of these changes over the disease course and their relationship with clinical parameters. In addition, we evaluated the effects of dopaminomimetics on resting-state oscillatory brain activity in levodopa-treated patients. MEG background oscillatory activity was studied in a group of 70 Parkinson's disease patients with varying disease duration and severity (including 18 de novo patients) as well as in 21 controls that were age-matched to the de novo patients. Whole head 151-channel MEG recordings were obtained in an eyes-closed resting-state condition. Levodopa-treated patients (N = 37) were examined both in a practically defined 'OFF' as well as in the 'ON' state. Relative spectral power was calculated for delta, theta, low alpha, high alpha, beta and gamma frequency bands and averaged for 10 cortical regions of interest (ROIs). Additionally, extensive clinical and neuropsychological testing was performed in all subjects. De novo Parkinson's disease patients showed widespread slowing of background MEG activity relative to controls. Changes included a widespread increase in theta and low alpha power, as well as a loss of beta power over all but the frontal ROIs and a loss of gamma power over all but the right occipital ROI. Neuropsychological assessment revealed abnormal perseveration in de novo patients, which was associated with increased low alpha power in centroparietal ROIs. In the whole group of Parkinson's disease patients, longer disease duration was associated with reduced low alpha power in the right temporal and right occipital ROI, but not with any other spectral power measure. No association was found between spectral power and disease stage, disease severity

  15. Repression of telomere-associated genes by microglia activation in neuropsychiatric disease.

    PubMed

    Kronenberg, Golo; Uhlemann, Ria; Schöner, Johanna; Wegner, Stephanie; Boujon, Valérie; Deigendesch, Nikolas; Endres, Matthias; Gertz, Karen

    2016-11-28

    Microglia senescence may promote neuropsychiatric disease. This prompted us to examine the relationship between microglia activation states and telomere biology. A panel of candidate genes associated with telomere maintenance, mitochondrial biogenesis, and cell-cycle regulation were investigated in M1- and M2-polarized microglia in vitro as well as in MACS-purified CD11b+ microglia/brain macrophages from models of stroke, Alzheimer's disease, and chronic stress. M1 polarization, ischemia, and Alzheimer pathology elicited a strikingly similar transcriptomic profile with, in particular, reduced expression of murine Tert. Our results link classical microglia activation with repression of telomere-associated genes, suggesting a new mechanism underlying microglia dysfunction.

  16. Is gardening a stimulating activity for people with advanced Huntington's disease?

    PubMed

    Spring, Josephine A; Viera, Marc; Bowen, Ceri; Marsh, Nicola

    2014-11-01

    This study evaluated adapted gardening as an activity for people with advanced Huntington's disease (HD) and explored its therapeutic aspects. Visitors and staff completed a questionnaire and participated in structured interviews to capture further information, whereas a pictorial questionnaire was designed for residents with communication difficulties. Staff reported that gardening was a constructive, outdoor activity that promoted social interaction, physical activity including functional movement and posed cognitive challenges. Half the staff thought the activity was problem free and a third used the garden for therapy. Visitors used the garden to meet with residents socially. Despite their disabilities, HD clients enjoyed growing flourishing flowers and vegetables, labelling plants, being outside in the sun and the quiet of the garden. The garden is valued by all three groups. The study demonstrates the adapted method of gardening is a stimulating and enjoyable activity for people with advanced HD.

  17. Salivary Acetylcholinesterase Activity Is Increased in Parkinson's Disease: A Potential Marker of Parasympathetic Dysfunction

    PubMed Central

    Fedorova, Tatyana; Knudsen, Cindy Soendersoe; Mouridsen, Kim; Nexo, Ebba; Borghammer, Per

    2015-01-01

    Introduction. Decreased salivary flow and xerostomia are frequent findings in Parkinson's disease (PD), possibly caused by alterations in the parasympathetic tonus. Here we explore salivary acetylcholinesterase (AChE) activity as a potential biomarker in PD. Methods. We measured salivary flow, AChE activity, and total protein concentration in 30 PD patients and 49 healthy controls. We also performed exploratory correlation analyses with disease duration, motor symptom severity, autonomic complaints, and other nonmotor symptoms. Results. PD patients displayed significantly decreased salivary flow rate, significantly increased salivary AChE activity, and total protein concentration. Importantly, the AChE activity/total protein ratio was significantly increased in PD patients, suggesting that increased AChE activity cannot be explained solely by upconcentration of saliva. The Unified PD Rating Scale (UPDRS) score displayed significant correlation with total salivary protein (P = 0.002) and near-significant correlation with salivary flow (P = 0.07). Color vision test scores were also significantly correlated with AChE activity (P = 0.04) and total protein levels (P = 0.002). Conclusion. Salivary AChE activity is increased in PD patients compared to healthy controls. Future studies are needed to elucidate whether this parameter reflects the extent of neuronal damage and parasympathetic denervation in the salivary glands of PD patients. PMID:25767737

  18. The classification of microglial activation phenotypes on neurodegeneration and regeneration in Alzheimer’s disease brain

    PubMed Central

    Varnum, Megan M.; Ikezu, Tsuneya

    2015-01-01

    Alzheimer’s disease (AD) is a neurodegenerative disease characterized by progressive decline of cognitive function and memory formation. There is no therapeutic that can halt or reverse its progression. Contemporary research suggests that age-dependent neuroinflammatory changes may play a significant role in the decreased neurogenesis and cognitive impairments in AD. The innate immune response is characterized by pro-inflammatory (M1) activation of macrophages and subsequent production of specific cytokines, chemokines, and reactive intermediates, followed by resolution and alternative activation for anti-inflammatory signaling (M2a) and wound healing (M2c). We propose that microglial activation phenotypes are analogous to those of macrophages and that their activation plays a significant role in regulating neurogenesis in the brain. Microglia undergo a switch from an M2- to an M1-skewed activation phenotype during aging. This review will assess the neuroimmunological studies that led to characterization of the different microglial activation states using AD mouse models. It will also discuss the roles of microglial activation on neurogenesis in AD and propose anti-inflammatory molecules as exciting therapeutic targets for research. Molecules like interleukin-4 and CD200 have proven to be important anti-inflammatory molecules in the regulation of neuroinflammation in the brain, and they will be discussed in detail for their therapeutic potential. PMID:22710659

  19. Behavioral and Locomotor Measurements Using an Open Field Activity Monitoring System for Skeletal Muscle Diseases

    PubMed Central

    Tatem, Kathleen S.; Quinn, James L.; Phadke, Aditi; Yu, Qing; Gordish-Dressman, Heather; Nagaraju, Kanneboyina

    2014-01-01

    The open field activity monitoring system comprehensively assesses locomotor and behavioral activity levels of mice. It is a useful tool for assessing locomotive impairment in animal models of neuromuscular disease and efficacy of therapeutic drugs that may improve locomotion and/or muscle function. The open field activity measurement provides a different measure than muscle strength, which is commonly assessed by grip strength measurements. It can also show how drugs may affect other body systems as well when used with additional outcome measures. In addition, measures such as total distance traveled mirror the 6 min walk test, a clinical trial outcome measure. However, open field activity monitoring is also associated with significant challenges: Open field activity measurements vary according to animal strain, age, sex, and circadian rhythm. In addition, room temperature, humidity, lighting, noise, and even odor can affect assessment outcomes. Overall, this manuscript provides a well-tested and standardized open field activity SOP for preclinical trials in animal models of neuromuscular diseases. We provide a discussion of important considerations, typical results, data analysis, and detail the strengths and weaknesses of open field testing. In addition, we provide recommendations for optimal study design when using open field activity in a preclinical trial. PMID:25286313

  20. The classification of microglial activation phenotypes on neurodegeneration and regeneration in Alzheimer's disease brain.

    PubMed

    Varnum, Megan M; Ikezu, Tsuneya

    2012-08-01

    Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive decline of cognitive function. There is no therapy that can halt or reverse its progression. Contemporary research suggests that age-dependent neuroinflammatory changes may play a significant role in the decreased neurogenesis and cognitive impairments in AD. The innate immune response is characterized by pro-inflammatory (M1) activation of macrophages and subsequent production of specific cytokines, chemokines, and reactive intermediates, followed by resolution and alternative activation for anti-inflammatory signaling (M2a) and wound healing (M2c). We propose that microglial activation phenotypes are analogous to those of macrophages and that their activation plays a significant role in regulating neurogenesis in the brain. Microglia undergo a switch from an M2- to an M1-skewed activation phenotype during aging. This review will assess the neuroimmunological studies that led to characterization of the different microglial activation states in AD mouse models. It will also discuss the roles of microglial activation on neurogenesis in AD and propose anti-inflammatory molecules as exciting therapeutic targets for research. Molecules such as interleukin-4 and CD200 have proven to be important anti-inflammatory mediators in the regulation of neuroinflammation in the brain, which will be discussed in detail for their therapeutic potential.

  1. Motor cortex activation in Parkinson's disease: dissociation of electrocortical and peripheral measures of response generation.

    PubMed

    Praamstra, P; Plat, E M; Meyer, A S; Horstink, M W

    1999-09-01

    This study investigated characteristics of motor cortex activation and response generation in Parkinson's disease with measures of electrocortical activity (lateralized readiness potential [LRP]), electromyographic activity (EMG), and isometric force in a noise-compatibility task. When presented with stimuli consisting of incompatible target and distractor elements asking for responses of opposite hands, patients were less able than control subjects to suppress activation of the motor cortex controlling the wrong response hand. This was manifested in the pattern of reaction times and in an incorrect lateralization of the LRP. Onset latency and rise time of the LRP did not differ between patients and control subjects, but EMG and response force developed more slowly in patients. Moreover, in patients but not in control subjects, the rate of development of EMG and response force decreased as reaction time increased. We hypothesize that this dissociation between electrocortical activity and peripheral measures in Parkinson's disease is the result of changes in motor cortex function that alter the relation between signal-related and movement-related neural activity in the motor cortex. In the LRP, this altered balance may obscure an abnormal development of movement-related neural activity.

  2. Disease Combinations Associated with Physical Activity Identified: The SMILE Cohort Study

    PubMed Central

    Dörenkamp, Sarah; Mesters, Ilse; Schepers, Jan; Vos, Rein; van den Akker, Marjan; Teijink, Joep; de Bie, Rob

    2016-01-01

    In the search of predictors of inadequate physical activity, an investigation was conducted into the association between multimorbidity and physical activity (PA). So far the sum of diseases used as a measure of multimorbidity reveals an inverse association. How specific combinations of chronic diseases are associated with PA remains unclear. The objective of this study is to identify clusters of multimorbidity that are associated with PA. Cross-sectional data of 3,386 patients from the 2003 wave of the Dutch cohort study SMILE were used. Ward's agglomerative hierarchical clustering was executed to establish multimorbidity clusters. Chi-square statistics were used to assess the association between clusters of chronic diseases and PA, measured in compliance with the Dutch PA guideline. The highest rate of PA guideline compliance was found in patients the majority of whom suffer from liver disease, back problems, rheumatoid arthritis, osteoarthritis, and inflammatory joint disease (62.4%). The lowest rate of PA guideline compliance was reported in patients with heart disease, respiratory disease, and diabetes mellitus (55.8%). Within the group of people with multimorbidity, those suffering from heart disease, respiratory disease, and/or diabetes mellitus may constitute a priority population as PA has proven to be effective in the prevention and cure of all three disorders. PMID:26881231

  3. Activated eosinophils and interleukin 5 expression in early recurrence of Crohn's disease.

    PubMed Central

    Dubucquoi, S; Janin, A; Klein, O; Desreumaux, P; Quandalle, P; Cortot, A; Capron, M; Colombel, J F

    1995-01-01

    Endoscopic recurrences after radical surgery for Crohn's disease are useful for studying the pathogenesis of initial lesions of Crohn's disease. Factors predisposing to recurrence are poorly understood, but it has been shown that eosinophilic infiltration of the neoileum may occur within a few weeks of resection. The aim of this study was to compare, in nine patients having an ileocolectomy, the infiltration of eosinophils and their activation state in normal and diseased areas of the neoileum, three months after surgery. Tissue eosinophils were studied by histochemical methods and electron microscopy. Mucosal expression of interleukin 5 (IL 5), an important eosinophil activating factor was studied using in situ hybridisation. Sixty per cent of patients had endoscopic recurrence at three months. Eosinophil infiltration was more pronounced in diseased than in endoscopically normal areas and was associated with a high expression of IL 5 mRNA. Ultrastructural analysis showed features of eosinophil activation, but no cytotoxic lesions of surrounding inflammatory or epithelial cells. This study suggests that local synthesis of IL 5 associated with eosinophil activation in the tissues could participate in early mucosal damage in Crohn's disease. Images Figure 1 Figure 2 Figure 3 PMID:7557575

  4. Viscothionin isolated from Korean mistletoe improves nonalcoholic fatty liver disease via the activation of adenosine monophosphate-activated protein kinase.

    PubMed

    Kim, Sokho; Lee, Dongho; Kim, Jae-Kyung; Kim, Jae-Hun; Park, Jong-Heum; Lee, Ju-Woon; Kwon, Jungkee

    2014-12-10

    The present study investigated the effects of viscothionin, a compound isolated from Korean mistletoe (Viscum album coloratum), on nonalcoholic fatty liver disease (NAFLD) in both in vitro and in vivo models. A connection was discovered between viscothionin and the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway, which is involved in lipid metabolism. Viscothionin was shown to significantly attenuate lipid accumulation in HepG2 cells treated with oleic acid, which induces lipid accumulation. Moreover, the phosphorylation of AMPK and acetyl-coenzyme A carboxylase in HepG2 cells was increased by viscothionin treatment. Viscothionin was orally administered to high fat diet-induced obese mice and subsequently histopathological analysis associated with AMPK signaling pathways was evaluated. A significant reduction in the extent of hepatic steatosis was revealed in viscothionin-treated obese mice. Thus, viscothionin mediates its beneficial effects on NAFLD via AMPK signaling pathways, suggesting that it may be a potential target for novel NAFLD treatments.

  5. Disease-Modifying Effects of M1 Muscarinic Acetylcholine Receptor Activation in an Alzheimer's Disease Mouse Model.

    PubMed

    Lebois, Evan P; Schroeder, Jason P; Esparza, Thomas J; Bridges, Thomas M; Lindsley, Craig W; Conn, P Jeffrey; Brody, David L; Daniels, J Scott; Levey, Allan I

    2017-03-07

    Alzheimer's disease (AD) is the leading cause of dementia worldwide, and currently no disease-modifying therapy is available to slow or prevent AD, underscoring the urgent need for neuroprotective therapies. Selective M1 muscarinic acetylcholine receptor (mAChR) activation is an attractive mechanism for AD therapy since M1 mediates key effects on memory, cognition, and behavior and has potential for disease-modifying effects on Aβ formation and tau phosphorylation. To validate M1 as a neuroprotective treatment target for AD, the M1-selective agonist, VU0364572, was chronically dosed to 5XFAD mice from a young age preceding Aβ pathology (2 months) to an age where these mice are known to display memory impairments (6 months). Chronic M1 activation prevented mice from becoming memory-impaired, as measured by Morris water maze (MWM) testing at 6 months of age. Additionally, M1 activation significantly reduced levels of soluble and insoluble Aβ40,42 in the cortex and hippocampus of these animals, as measured by ELISA and immunohistochemistry. Moreover, soluble hippocampal Aβ42 levels were strongly correlated with MWM memory impairments and M1 activation with VU0364572 abolished this correlation. Finally, VU0364572 significantly decreased oligomeric (oAβ) levels in the cortex, suggesting one mechanism whereby VU0364572 may be exerting its neuroprotective effects is by reducing the available oAβ pool in the brain. These findings suggest that chronic M1 activation has neuroprotective potential for preventing memory impairments and reducing neuropathology in AD. M1 activation therefore represents a promising avenue for preventative treatment, as well as a promising opportunity to combine symptomatic and disease-modifying effects for early AD treatment.

  6. Get Active

    MedlinePlus

    ... Basics: Health Benefits What are the benefits of physical activity? Physical activity increases your chances of living longer. ... pain Help you feel better about yourself Is physical activity for everyone? Yes! Physical activity is good for ...

  7. Small molecule adenosine 5'-monophosphate activated protein kinase (AMPK) modulators and human diseases.

    PubMed

    Rana, Sandeep; Blowers, Elizabeth C; Natarajan, Amarnath

    2015-01-08

    Adenosine 5'-monophosphate activated protein kinase (AMPK) is a master sensor of cellular energy status that plays a key role in the regulation of whole-body energy homeostasis. AMPK is a serine/threonine kinase that is activated by upstream kinases LKB1, CaMKKβ, and Tak1, among others. AMPK exists as αβγ trimeric complexes that are allosterically regulated by AMP, ADP, and ATP. Dysregulation of AMPK has been implicated in a number of metabolic diseases including type 2 diabetes mellitus and obesity. Recent studies have associated roles of AMPK with the development of cancer and neurological disorders, making it a potential therapeutic target to treat human diseases. This review focuses on the structure and function of AMPK, its role in human diseases, and its direct substrates and provides a brief synopsis of key AMPK modulators and their relevance in human diseases.

  8. Disease activity patterns over time in patients with SLE: analysis of the Hopkins Lupus Cohort

    PubMed Central

    Györi, Noémi; Giannakou, Ioanna; Chatzidionysiou, Katerina; Magder, Laurence; van Vollenhoven, Ronald F; Petri, Michelle

    2017-01-01

    Objective To describe SLE disease activity patterns in the Hopkins Lupus Cohort. Methods Disease activity was studied in 1886 patients followed-up for 1–28 years. Disease activity patterns were defined using (1) Physician Global Assessment (PGA) and (2) modified SLE Disease Activity Index (M-SLEDAI) as follows: long quiescent (LQ), M-SLEDAI=0/PGA=0 at all visits; relapsing-remitting (RR), periods of activity (M-SLEDAI>0/PGA>0) interspersed with inactivity (M-SLEDAI=0/PGA=0); chronic active (CA), M-SLEDAI>0/PGA>0 at all visits. The pattern of first 3 consecutive follow-up years was determined in 916 patients as: persistent LQ (pLQ), persistent RR (pRR) and persistent CA (pCA), LQ, RR and CA pattern in each of the 3 years, respectively; mixed, at least two different pattern types were identified. Results The RR pattern accounted for the greatest proportion of follow-up time both by M-SLEDAI and PGA, representing 53.8% and 49.9% of total patient-years, respectively. The second most frequent pattern was LQ based on M-SLEDAI (30.7%) and CA based on PGA (40.4%). For the first 3-year intervals, the mixed pattern type was the most common (56.6%). The pRR was the second most frequent (M-SLEDAI 33.3%, PGA 26.5%), while pLQ (M-SLEDAI 6.4%, PGA 0.7%) and pCA were less frequent (M-SLEDAI 3.7%, PGA 16.3%). Conclusions The RR pattern was the most prevalent pattern. LQ was achieved in a subset of patients, using the M-SLEDAI. However, the PGA captured mild activity missed on the M-SLEDAI in these patients. Over a 3-year perspective, less than half of patients maintained their original pattern. PMID:28243457

  9. Deficient Rab11 activity underlies glucose hypometabolism in primary neurons of Huntington's disease mice

    SciTech Connect

    Li, Xueyi; Valencia, Antonio; McClory, Hollis; Sapp, Ellen; Kegel, Kimberly B.; DiFiglia, Marian

    2012-05-18

    Highlights: Black-Right-Pointing-Pointer Primary Huntington's disease neurons are impaired in taking up glucose. Black-Right-Pointing-Pointer Rab11 modulates glucose uptake in neurons. Black-Right-Pointing-Pointer Increasing Rab11 activity attenuates the glucose uptake defect in disease neurons. Black-Right-Pointing-Pointer We provide a novel mechanism for glucose hypometabolism in Huntington's disease. -- Abstract: Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene. Positron emission tomography studies have revealed a decline in glucose metabolism in the brain of patients with HD by a mechanism that has not been established. We examined glucose utilization in embryonic primary cortical neurons of wild-type (WT) and HD knock-in mice, which have 140 CAG repeats inserted in the endogenous mouse huntingtin gene (HD{sup 140Q/140Q}). Primary HD{sup 140Q/140Q} cortical neurons took up significantly less glucose than did WT neurons. Expression of permanently inactive and permanently active forms of Rab11 correspondingly altered glucose uptake in WT neurons, suggesting that normal activity of Rab11 is needed for neuronal uptake of glucose. It is known that Rab11 activity is diminished in HD{sup 140Q/140Q} neurons. Expression of dominant active Rab11 to enhance the activity of Rab11 normalized glucose uptake in HD{sup 140Q/140Q} neurons. These results suggest that deficient activity of Rab11 is a novel mechanism for glucose hypometabolism in HD.

  10. Glycoprotein YKL-40: a novel biomarker of chronic graft-vs-host disease activity and severity?

    PubMed Central

    Duraković, Nadira; Krečak, Ivan; Perić, Zinaida; Milošević, Milan; Desnica, Lana; Pulanić, Dražen; Pusic, Iskra; Kušec, Vesna; Vrhovac, Radovan; Pavletic, Steven Z.; Nemet, Damir

    2016-01-01

    Aim To investigate whether increased YKL-40 levels positively correlate with graft-vs-host disease (cGVHD) activity and severity and if YKL-40 could serve as a disease biomarker. Methods This case-control study was conducted at the University Hospital Centre Zagreb from July 2013 to October 2015. 56 patients treated with hematopoietic stem cell transplantation (HSCT) were included: 35 patients with cGVHD and 21 without cGVHD. There was no difference between groups in age, sex, median time from transplant to study enrollment, intensity of conditioning, type of donor, or source of stem cells. Blood samples were collected at study enrollment and YKL-40 levels were measured with ELISA. Disease activity was estimated using Clinician’s Impression of Activity and Intensity of Immunosuppression scales and disease severity using Global National Institutes of Health (NIH) score. Results YKL-40 levels were significantly higher in cGVHD patients than in controls (P = 0.003). The difference remained significant when patients with myelofibrosis were excluded from the analysis (P = 0.017). YKL-40 level significantly positively correlated with disease severity (P < 0.001; correlation coefficient 0.455), and activity estimated using Clinician’s Impression of Activity (P = 0.016; correlation coefficient 0.412) but not using Intensity of Immunosuppression (P = 0.085; correlation coefficient 0.296). Conclusion YKL-40 could be considered a biomarker of cGVHD severity and activity. However, validation in a larger group of patients is warranted, as well as longitudinal testing of YKL-40 levels in patients at risk of developing cGVHD. PMID:27374825

  11. Activation of Blood Coagulation in Two Prototypic Autoimmune Skin Diseases: A Possible Link with Thrombotic Risk.

    PubMed

    Cugno, Massimo; Tedeschi, Alberto; Borghi, Alessandro; Bucciarelli, Paolo; Asero, Riccardo; Venegoni, Luigia; Griffini, Samantha; Grovetti, Elena; Berti, Emilio; Marzano, Angelo Valerio

    2015-01-01

    Coagulation activation has been demonstrated in two prototypic autoimmune skin diseases, chronic autoimmune urticaria and bullous pemphigoid, but only the latter is associated with increased thrombotic risk. Two markers of coagulation activation (prothrombin fragment F1+2 and fibrin fragment D-dimer) were measured by immunoenzymatic methods in plasma samples from 30 patients with active chronic autoimmune urticaria, positive for autologous serum skin test, 30 patients with active bullous pemphigoid and 30 healthy subjects. In skin biopsies, tissue factor expression was evaluated by both immunohistochemistry and in situ hybridization. F1+2 and D-dimer levels were higher in active chronic autoimmune urticaria (276.5±89.8 pmol/L and 5.56±4.40 nmol/L, respectively) than in controls (145.2±38.0 pmol/L and 1.06±0.25 nmol/L; P=0.029 and P=0.011) and were much higher in active bullous pemphigoid (691.7±318.7 pmol/L and 15.24±9.09 nmol/L, respectively) (P<0.0001). Tissue factor positivity was evident in skin biopsies of both disorders with higher intensity in bullous pemphigoid. F1+2 and D-dimer, during remission, were markedly reduced in both disorders. These findings support the involvement of coagulation activation in the pathophysiology of both diseases. The strong systemic activation of coagulation in bullous pemphigoid may contribute to increase the thrombotic risk and provides the rationale for clinical trials on anticoagulant treatments in this disease.

  12. Role of Inflammasome Activation in the Pathophysiology of Vascular Diseases of the Neurovascular Unit

    PubMed Central

    Mohamed, Islam N.; Ishrat, Tauheed; Fagan, Susan C.

    2015-01-01

    Abstract Significance: Inflammation is the standard double-edged defense mechanism that aims at protecting the human physiological homeostasis from devastating threats. Both acute and chronic inflammation have been implicated in the occurrence and progression of vascular diseases. Interference with components of the immune system to improve patient outcome after ischemic injury has been uniformly unsuccessful. There is a need for a deeper understanding of the innate immune response to injury in order to modulate, rather than to block inflammation and improve the outcome for vascular diseases. Recent Advances: Nucleotide-binding oligomerization domain-like receptors or NOD-like receptor proteins (NLRPs) can be activated by sterile and microbial inflammation. NLR family plays a major role in activating the inflammasome. Critical Issues: The aim of this work is to review recent findings that provided insights into key inflammatory mechanisms and define the place of the inflammasome, a multi-protein complex involved in instigating inflammation in neurovascular diseases, including retinopathy, neurodegenerative diseases, and stroke. Future Directions: The significant contribution of NLRP-inflammasome activation to vascular disease of the neurovascular unit in the brain and retina suggests that therapeutic strategies focused on specific targeting of inflammasome components could significantly improve the outcomes of these diseases. Antioxid. Redox Signal. 22, 1188–1206. PMID:25275222

  13. 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

  14. Effects of training and weight support on muscle activation in Parkinson's disease.

    PubMed

    Rose, Martin H; Løkkegaard, Annemette; Sonne-Holm, Stig; Jensen, Bente R

    2013-12-01

    The aim of this study was to investigate the effect of high-intensity locomotor training on knee extensor and flexor muscle activation and adaptability to increased body-weight (BW) support during walking in patients with Parkinson's disease (PD). Thirteen male patients with idiopathic PD and eight healthy participants were included. The PD patients completed an 8-week training program on a lower-body, positive-pressure treadmill. Knee extensor and flexor muscles activation during steady treadmill walking (3 km/h) were measured before, at the mid-point, and after training. Increasing BW support decreased knee extensor muscle activation (normalization) and increased knee flexor muscle activation (abnormal) in PD patients when compared to healthy participants. Training improved flexor peak muscle activation adaptability to increased (BW) support during walking in PD patients. During walking without BW support shorter knee extensor muscle off-activation time and increased relative peak muscle activation was observed in PD patients and did not improve with 8 weeks of training. In conclusion, patients with PD walked with excessive activation of the knee extensor and flexor muscles when compared to healthy participants. Specialized locomotor training may facilitate adaptive processes related to motor control of walking in PD patients.

  15. 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.

  16. Interference of PR3-ANCA with the enzymatic activity of PR3: differences in patients during active disease or remission of Wegener's granulomatosis.

    PubMed

    van der Geld, Y M; Tool, A T J; Videler, J; de Haas, M; Tervaert, J W Cohen; Stegeman, C A; Limburg, P C; Kallenberg, C G M; Roos, D

    2002-09-01

    Anti-neutrophil cytoplasmic antibodies (ANCA) against proteinase 3 (PR3) are strongly associated with Wegener's granulomatosis (WG) and are thought to be involved in its pathogenesis. Levels of PR3-ANCA do not always correspond to clinical disease activity. To investigate the relationship between functional effects of PR3-ANCA and disease activity, we tested the effect of IgG samples from sera of 43 WG patients, taken during active disease or remission, for their capacity to interfere with the proteolytic activity of PR3. Furthermore, longitudinal sera of seven WG patients were included. The enzymatic activity of PR3 was determined (1) with casein or with a small synthetic substrate and (2) by complexation of PR3 with alpha1-antitrypsin (alpha1-AT). With a fixed concentration (100 microg/ml) of IgG, PR3-ANCA from patients during an active phase of WG had a higher inhibitory capacity towards the proteolytic activity of PR3 and complexation of PR3 with alpha1-AT than did PR3-ANCA from WG patients during remission. However, the number of PR3-ANCA units that gave 50% inhibition of the PR3 enzymatic activity and its complexation with alpha1-AT was lower for patients during remission than for patients during an active phase of WG, indicating a stronger inhibitory capacity at a molar base. In conclusion, PR3-ANCA from patients during remission had a relatively higher inhibitory capacity towards the enzymatic activity of PR3 than PR3-ANCA from patients during an active phase. This may indicate that during active disease the ANCA titre is increased, but the number of active ANCA molecules that recognize the enzyme-inhibiting epitopes is not increased.

  17. Bactericidal Activity Does Not Predict Sterilizing Activity: The Case of Rifapentine in the Murine Model of Mycobacterium ulcerans Disease

    PubMed Central

    Almeida, Deepak V.; Converse, Paul J.; Li, Si-Yang; Tyagi, Sandeep; Nuermberger, Eric L.; Grosset, Jacques H.

    2013-01-01

    Background Since 2004, treatment of Mycobacterium ulcerans disease, or Buruli ulcer, has shifted from surgery to daily treatment with streptomycin (STR) + rifampin (RIF) for 8 weeks. For shortening treatment duration, we tested the potential of daily rifapentine (RPT), a long-acting rifamycin derivative, as a substitute for RIF. Methodology/Principal Findings BALB/c mice were infected with M. ulcerans in the right hind footpad and treated either daily (7/7) with STR+RIF or five days/week (5/7) with STR+RIF or STR+RPT for 4 weeks, beginning 28 days after infection when CFU counts were 4.88±0.51. The relative efficacy of the drug treatments was compared by footpad CFU counts during treatment and median time to footpad swelling after treatment cessation as measure of sterilizing activity. All drug treatments were bactericidal. After 1 week of treatment, the decline in CFU counts was significantly greater in treated mice but not different between the three treated groups. After 2 weeks of treatment, the decline in CFU was greater in mice treated with STR+RPT 5/7 than in mice treated with STR+RIF 7/7 and STR+RIF 5/7. After 3 and 4 weeks of treatment, CFU counts were nil in mice treated with STR+RPT and reduced by more than 3 and 4 logs in mice treated with STR+RIF 5/7 and STR+RIF 7/7, respectively. In sharp contrast to the bactericidal activity, the sterilizing activity was not different between all drug regimens although it was in proportion to the treatment duration. Conclusions/Significance The better bactericidal activity of daily STR+RIF and especially of STR+RPT did not translate into better prevention of relapse, possibly because relapse-freecure after treatment of Buruli ulcer is more related to the reversal of mycolactone-induced local immunodeficiency by drug treatment rather than to the bactericidal potency of drugs. PMID:23469308

  18. Assessment of Activity of Crohn Disease by Diffusion-Weighted Magnetic Resonance Imaging.

    PubMed

    Li, Xue-Hua; Sun, Can-Hui; Mao, Ren; Zhang, Zhong-Wei; Jiang, Xiao-Song; Pui, Margaret H; Chen, Min-Hu; Li, Zi-Ping

    2015-10-01

    To assess the diagnostic efficacy of diffusion-weighted MR imaging (DWI) for evaluating inflammatory activity in patients with Crohn's disease (CD). A total of 47 CD patients underwent MR enterography (MRE) and DWI using 3 b values of 50, 400, and 800 s/mm. Apparent diffusion coefficients (ADCs) of inflamed and normal bowel wall were calculated. The conventional MRE findings and DWI signal intensities were qualitatively scored from 0 to 3. The correlation between Crohn disease activity index (CDAI) and both ADCs and magnetic resonance imaging scores was analyzed. Receiver-operating characteristic curve analysis was used to determine the diagnostic accuracy of CD activity. Of the 47 patients, 25 were active CD (CDAI≥150) and 22 were inactive (CDAI<150). Diffusion-weighted MR imaging and MRE + DWI scores of active CD were significantly higher than that of inactive CD (both P < 0.001). Apparent diffusion coefficients in inflamed segments of active CD were lower than that of inactive CD (P < 0.001). The DWI scores (r = 0.74, P < 0.001), ADCs (r = -0.71, P < 0.001), MRE scores (r = 0.54, P < 0.001), and MRE + DWI scores (r = 0.66, P < 0.001) were all correlated with CDAI. The areas under the receiver-operating characteristics curves for ADCs, DWI scores, MRE scores, and MRE + DWI scores ranged from 0.83 to 0.98. The threshold ADC value of 1.17 × 10 mm/s allowed differentiation of active from inactive CD with 100% sensitivity and 88% specificity. Diffusion-weighted MR imaging and ADC correlated with CD activity, and had excellent diagnostic accuracy for differentiating active from inactive CD.

  19. 3-Hydroxyflavone and structural analogues differentially activate pregnane X receptor: Implication for inflammatory bowel disease.

    PubMed

    Lau, Aik Jiang; Chang, Thomas K H

    2015-10-01

    Pregnane X receptor (PXR; NR1I2) is a member of the superfamily of nuclear receptors that regulates the expression of genes involved in various biological processes, including drug transport and biotransformation. In the present study, we investigated the effect of 3-hydroxyflavone and its structurally-related analogues on PXR activity. 3-Hydroxyflavone, galangin, kaempferol, querceetin, isorhamnetin, and tamarixetin, but not but not datiscetin, morin, myricetin, or syringetin, activated mouse PXR, as assessed in a cell-based reporter gene assay. By comparison, 3-hydroxyflavone activated rat PXR, whereas 3-hydroxyflavone, galangin, quercetin, isorhamnetin, and tamarixetin activated human PXR (hPXR). A time-resolved fluorescence resonance energy transfer competitive ligand-binding assay showed binding to the ligand-binding domain of hPXR by 3-hydroxyflavone, galangin, quercetin, isorhamnetin, and tamarixetin. 3-Hydroxyflavone and galangin, but not quercetin, isorhamnetin, or tamarixetin, recruited steroid receptor coactivator (SRC)-1, SRC-2, and SRC-3 to hPXR. In LS180 human colon adenocarcinoma cells, 3-hydroxyflavone, quercetin, and tamarixetin increased CYP3A4, CYP3A5, and ABCB1 mRNA expression, whereas galangin and isorhamnetin increased CYP3A4 and ABCB1 but not CYP3A5 mRNA expression. Datiscetin, kaempferol, morin, myricetin, and syringetin did not attenuate the extent of hPXR activation by rifampicin, suggesting they are not hPXR antagonists. Overall, flavonols activate PXR in an analogue-specific and species-dependent manner. Substitution at the C2' or C5' position of 3-hydroxyflavone with a hydroxyl or methoxy group rendered it incapable of activating hPXR. Understanding the structure-activity relationship of flavonols in hPXR activation may facilitate nutraceutical development efforts in the treatment of PXR-associated intestinal diseases, such as inflammatory bowel disease.

  20. 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

  1. Daytime Physical Activity and Sleep in Hospitalized Older Adults: Association with Demographic Characteristics and Disease Severity

    PubMed Central

    Beveridge, Claire; Knutson, Kristen; Spampinato, Lisa; Flores, Andrea; Meltzer, David O.; Van Cauter, Eve; Arora, Vineet M.

    2016-01-01

    OBJECTIVES To assess objectively measured daytime physical activity and sleep duration and efficiency in hospitalized older adults and explore associations with demographic characteristics and disease severity. DESIGN Prospective cohort study. SETTING University of Chicago Medical Center general medicine wards. PARTICIPANTS Community-dwelling inpatients aged 50 and older (N = 120) MEASUREMENTS Physical activity and sleep were measured using wrist accelerometers. Information on Charlson Comorbidity Index and length of stay was collected from charts. Random-effects linear regression analysis was used to examine the association between in-hospital sleep and physical activity. RESULTS From March 2010 to May 2013, 120 participants wore wrist actigraphy monitors for at least 2 nights and 1 intervening day. Median activity level over the waking period was 77 counts/min (interquartile range 51–121 counts/min), an activity level that approximately corresponds to sitting while watching television (65 counts/min). Mean sleep duration the night before the activity interval was 289 ± 157 minutes, and mean sleep efficiency the night before the activity interval was 65.2 ± 26.9%. Mean activity counts/min were lowest for the oldest participants (oldest quartile 62, 95% confidence interval (CI) = 50–75; youngest quartile 121, 95% CI = 98–145, trend test P < .001) and those with highest Charlson Comorbidity Index (highest tertile 71, 95% CI = 60–83; lowest tertile 125, 95% CI = 104–147, trend test P = .01). Controlling for severity of illness and demographic characteristics, activity declined by 3 counts/min (95% CI = −5.65 to −0.43, P = .02) for each additional hour of inpatient sleep. CONCLUSION Older, sicker adults are less physically active during hospitalization. In contrast to studies in the community, inpatients who slept more were not more active. This may highlight that need for sleep is greater in the hospital than in the community. PMID:26131982

  2. [Effects of physical activity on cancer risk and disease progression after cancer diagnosis].

    PubMed

    Steindorf, K; Schmidt, M; Ulrich, C

    2012-01-01

    Numerous epidemiologic studies have demonstrated that regular physical activity convincingly reduces risk for colon cancer, probably for endometrium and postmenopausal breast cancer, and possibly for premenopausal breast, prostate, lung, and pancreas cancer. Relative risk reductions range from 10-30%. On the absolute scale about 9-19% of the most frequent cancers can be attributed to a lack of sufficient physical activity. Thus, exercise, as a modifiable health behavior, has a strong potential for primary cancer prevention. Current recommendations call for at least 30-60 min of moderate to vigorous activity daily. Physical activity is also increasingly gaining importance in cancer treatment and is now considered to be feasible, safe, and even recommended in almost all stages of disease. Randomized-controlled trials show that disease- and treatment-related symptoms, such as fatigue, sleep disorders, and depression which sometimes limit quality of life in cancer patients over years, can be reduced by physical activity. For disease-specific and total mortality, clinical studies are not yet available. However, preliminary observational studies with breast, colon, and prostate cancer patients show risk reductions.

  3. A new paradigm for the treatment of Alzheimer's disease: targeting vascular activation.

    PubMed

    Grammas, Paula; Martinez, Joseph; Sanchez, Alma; Yin, Xiangling; Riley, Jarred; Gay, Dylan; Desobry, Katherine; Tripathy, Debjani; Luo, Jinhua; Evola, Marianne; Young, Alice

    2014-01-01

    No disease-modifying therapies are currently available for Alzheimer's disease (AD), a neurodegenerative disorder that affects more than 36 million people worldwide. Although cardiovascular risk factors such as hypertension and diabetes are increasingly implicated as contributing to the development of AD, the mechanisms whereby these factors influence pathological processes in the AD brain have not been defined. Here we propose, for the first time, vascular activation as a relevant mechanism in AD pathogenesis. We explore this hypothesis in two transgenic AD animal models: AD2576APPSwe (AD2576) and LaFerla 3xTg (3xTgAD) mice using the vascular activation inhibitor sunitinib. Our data show that in both AD animal models, the cerebrovasculature is activated and overexpresses amyloid beta, thrombin, tumor necrosis factor alpha, interleukin-1 beta, interleukin-6, and matrix metalloproteinase 9. Oral administration of sunitinib significantly reduces vascular expression of these proteins. Furthermore, sunitinib improves cognitive function, as assessed by several behavioral paradigms, in both AD animal models. Finally, oxidant injury of brain endothelial cells in culture, resulting in expression of inflammatory proteins, is mitigated by sunitinib. The current data, as well as published studies showing cerebrovascular activation in human AD, support further exploration of vascular-based mechanisms in AD pathogenesis. New thinking about AD pathogenesis and novel, effective treatments are urgently needed. Identification of "vascular activation" as a heretofore unexplored target could stimulate translational investigations in this newly defined area, leading to innovative therapeutic approaches for the treatment of this devastating disease.

  4. Multifunctional activity of polyphenolic compounds associated with a potential for Alzheimer's disease therapy from Ecklonia cava.

    PubMed

    Choi, Byoung Wook; Lee, Hye Sook; Shin, Hyeon-Cheol; Lee, Bong Ho

    2015-04-01

    Five polyphenols were isolated and purified from a brown alga Ecklonia cava. These compounds showed diverse biological activities such as antioxidative, antiinflammatory, and enzyme inhibitory activities. This led us to investigate the potential of these compounds as Alzheimer's disease drugs. All of the compounds showed moderate acetylcholinesterase inhibitory activity in a micromolar range (IC50 from 16.0 to 96.3 μM). For butyrylcholinesterase, a new target for the treatment of Alzheimer's disease, phlorofucofuroeckol-A (PFF-A), showed a particularly potent inhibitory activity (IC50 0.95 μM), which is over 100-fold greater than for acetylcholinesterase. These compounds inhibited glycogen synthase kinase 3 beta, which is related to the formation of hyperphosphorylated tau and generation Aβ. Bieckol and PFF-A inhibited amyloid precursor protein biosynthesis. PFF-A also showed very strong β-secretase inhibitory activity with IC50 of submicromole. These results render these compounds as interesting potential drug candidates for Alzheimer's disease.

  5. Physical Activity and Sport Participation in Youth with Congenital Heart Disease: Perceptions of Children and Parents

    ERIC Educational Resources Information Center

    Moola, Fiona; Faulkner, Guy E. J.; Kirsh, Joel A.; Kilburn, Jennifer

    2008-01-01

    This study explored perceptions toward physical activity and sport in the lives of youth with congenital heart disease. Thirteen cardiac participants were interviewed in the presence of their parents, and a process of inductive analysis was conducted. Sport was not considered a valued pursuit despite the belief that it is essential for the…

  6. Search for Antiprotozoal Activity in Herbal Medicinal Preparations; New Natural Leads against Neglected Tropical Diseases.

    PubMed

    Llurba Montesino, Núria; Kaiser, Marcel; Brun, Reto; Schmidt, Thomas J

    2015-08-04

    Sleeping sickness, Chagas disease, Leishmaniasis, and Malaria are infectious diseases caused by unicellular eukaryotic parasites ("protozoans"). The three first mentioned are classified as Neglected Tropical Diseases (NTDs) by the World Health Organization and together threaten more than one billion lives worldwide. Due to the lack of research interest and the high increase of resistance against the existing treatments, the search for effective and safe new therapies is urgently required. In view of the large tradition of natural products as sources against infectious diseases [1,2], the aim of the present study is to investigate the potential of legally approved and marketed herbal medicinal products (HMPs) as antiprotozoal agents. Fifty-eight extracts from 53 HMPs on the German market were tested by a Multiple-Target-Screening (MTS) against parasites of the genera Leishmania, Trypanosoma, and Plasmodium. Sixteen HMPs showed in vitro activity against at least one of the pathogens (IC50 < 10 µg/mL). Six extracts from preparations of Salvia, Valeriana, Hypericum, Silybum, Arnica, and Curcuma exhibited high activity (IC50 < 2.5 µg/mL). They were analytically characterized by UHPLC/ESI-QqTOF-MSMS and the activity-guided fractionation of the extracts with the aim to isolate and identify the active compounds is in progress.

  7. 25-hydroxyvitamin D levels and juvenile idiopathic arthritis: is there an association with disease activity?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To examine the association between serum levels of 25-hydroxyvitamin D [25(OH)D] and disease activity in juvenile idiopathic arthritis (JIA), to determine the prevalence of vitamin D (VD) deficiency [25(OH)D=19 ng/ml] and insufficiency [25(OH)D 20-29 ng/ml], and to determine factors associated with ...

  8. Significance of peroxisome proliferator-activated receptors in the cardiovascular system in health and disease.

    PubMed

    Robinson, Emma; Grieve, David J

    2009-06-01

    Peroxisome proliferator-activated receptors (PPARs) are ligand-activated nuclear transcription factors that belong to the nuclear receptor superfamily. Three isoforms of PPAR have been identified, alpha, delta and gamma, which play distinct roles in the regulation of key metabolic processes, such as glucose and lipid redistribution. PPARalpha is expressed predominantly in the liver, kidney and heart, and is primarily involved in fatty acid oxidation. PPARgamma is mainly associated with adipose tissue, where it controls adipocyte differentiation and insulin sensitivity. PPARdelta is abundantly and ubiquitously expressed, but as yet its function has not been clearly defined. Activators of PPARalpha (fibrates) and gamma (thiazolidinediones) have been used clinically for a number of years in the treatment of hyperlipidaemia and to improve insulin sensitivity in diabetes. More recently, PPAR activation has been found to confer additional benefits on endothelial function, inflammation and thrombosis, suggesting that PPAR agonists may be good candidates for the treatment of cardiovascular disease. In this regard, it has been demonstrated that PPAR activators are capable of reducing blood pressure and attenuating the development of atherosclerosis and cardiac hypertrophy. This review will provide a detailed discussion of the current understanding of basic PPAR physiology, with particular reference to the cardiovascular system. It will also examine the evidence supporting the involvement of the different PPAR isoforms in cardiovascular disease and discuss the current and potential future clinical applications of PPAR activators.

  9. Circulating ADAM17 Level Reflects Disease Activity in Proteinase-3 ANCA-Associated Vasculitis.

    PubMed

    Bertram, Anna; Lovric, Svjetlana; Engel, Alissa; Beese, Michaela; Wyss, Kristin; Hertel, Barbara; Park, Joon-Keun; Becker, Jan U; Kegel, Johanna; Haller, Hermann; Haubitz, Marion; Kirsch, Torsten

    2015-11-01

    ANCA-associated vasculitides are characterized by inflammatory destruction of small vessels accompanied by enhanced cleavage of membrane-bound proteins. One of the main proteases responsible for ectodomain shedding is disintegrin and metalloproteinase domain-containing protein 17 (ADAM17). Given its potential role in aggravating vascular dysfunction, we examined the role of ADAM17 in active proteinase-3 (PR3)-positive ANCA-associated vasculitis (AAV). ADAM17 concentration was significantly increased in plasma samples from patients with active PR3-AAV compared with samples from patients in remission or from other controls with renal nonvascular diseases. Comparably, plasma levels of the ADAM17 substrate syndecan-1 were significantly enhanced in active AAV. We also observed that plasma-derived ADAM17 retained its specific proteolytic activity and was partly located on extracellular microparticles. Transcript levels of ADAM17 were increased in blood samples of patients with active AAV, but those of ADAM10 or tissue inhibitor of metalloproteinases 3, which inhibits ADAMs, were not. We also performed a microRNA (miR) screen and identified miR-634 as significantly upregulated in blood samples from patients with active AAV. In vitro, miR-634 mimics induced a proinflammatory phenotype in monocyte-derived macrophages, with enhanced expression and release of ADAM17 and IL-6. These data suggest that ADAM17 has a prominent role in AAV and might account for the vascular complications associated with this disease.

  10. Circulating ADAM17 Level Reflects Disease Activity in Proteinase-3 ANCA-Associated Vasculitis

    PubMed Central

    Bertram, Anna; Lovric, Svjetlana; Engel, Alissa; Beese, Michaela; Wyss, Kristin; Hertel, Barbara; Park, Joon-Keun; Becker, Jan U.; Kegel, Johanna; Haller, Hermann; Haubitz, Marion

    2015-01-01

    ANCA-associated vasculitides are characterized by inflammatory destruction of small vessels accompanied by enhanced cleavage of membrane-bound proteins. One of the main proteases responsible for ectodomain shedding is disintegrin and metalloproteinase domain-containing protein 17 (ADAM17). Given its potential role in aggravating vascular dysfunction, we examined the role of ADAM17 in active proteinase-3 (PR3)-positive ANCA-associated vasculitis (AAV). ADAM17 concentration was significantly increased in plasma samples from patients with active PR3-AAV compared with samples from patients in remission or from other controls with renal nonvascular diseases. Comparably, plasma levels of the ADAM17 substrate syndecan-1 were significantly enhanced in active AAV. We also observed that plasma-derived ADAM17 retained its specific proteolytic activity and was partly located on extracellular microparticles. Transcript levels of ADAM17 were increased in blood samples of patients with active AAV, but those of ADAM10 or tissue inhibitor of metalloproteinases 3, which inhibits ADAMs, were not. We also performed a microRNA (miR) screen and identified miR-634 as significantly upregulated in blood samples from patients with active AAV. In vitro, miR-634 mimics induced a proinflammatory phenotype in monocyte-derived macrophages, with enhanced expression and release of ADAM17 and IL-6. These data suggest that ADAM17 has a prominent role in AAV and might account for the vascular complications associated with this disease. PMID:25788529

  11. Gender, body mass index and rheumatoid arthritis disease activity: results from the QUEST-RA study

    PubMed Central

    Jawaheer, Damini; Olsen, Jørn; Lahiff, Maureen; Forsberg, Sinikka; Lähteenmäki, Jukka; Silveira, Ines Guimaraes da; Rocha, Francisco Airton; Laurindo, Ieda Maria Magalhães; Mota, Licia Maria Henrique da; Drosos, Alexandros A.; Murphy, Eithne; Sheehy, Claire; Quirke, Edel; Cutolo, Maurizio; Rexhepi, Sylejman; Dadoniene, Jolanta; Verstappen, Suzan M.M.; Sokka, Tuulikki

    2010-01-01

    Objective To investigate whether body mass index (BMI), as a proxy for body fat, influences rheumatoid arthritis (RA) disease activity in a gender-specific manner. Methods Consecutive patients with RA were enrolled from 25 countries into the QUEST-RA program between 2005 and 2008. Clinical and demographic data were collected by treating rheumatologists and by patient self-report. Distributions of Disease Activity Scores (DAS28), BMI, age, and disease duration were assessed for each country and for the entire dataset; mean values between genders were compared using Student’s t-tests. An association between BMI and DAS28 was investigated using linear regression, adjusting for age, disease duration and country. Results A total of 5,161 RA patients (4,082 women and 1,079 men) were included in the analyses. Overall, women were younger, had longer disease duration, and higher DAS28 scores than men, but BMI was similar between genders. The mean DAS28 scores increased with increasing BMI from normal to overweight and obese, among women, whereas the opposite trend was observed among men. Regression results showed BMI (continuous or categorical) to be associated with DAS28. Compared to the normal BMI range, being obese was associated with a larger difference in mean DAS28 (0.23, 95% CI: 0.11, 0.34) than being overweight (0.12, 95% CI: 0.03, 0.21); being underweight was not associated with disease activity. These associations were more pronounced among women, and were not explained by any single component of the DAS28. Conclusion BMI appears to be associated with RA disease activity in women, but not in men. PMID:20810033

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

    PubMed Central

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

    1987-01-01

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

  13. [Multi-organ failure as first clinical sign of macrophage activation syndrome in childhood Still's disease].

    PubMed

    López-Sánchez, M; Rubio-López, I; Obeso-González, T; Teja-Barbero, J L; Santidrián-Miguel, J P; Peiro-Callizo, E

    2010-10-01

    Macrophage activation syndrome is a form of secondary haemophagocytic lymphohistiocytosis seen in the context of rheumatic diseases. It is seen most frequently in association with systemic onset juvenile arthritis or childhood Still's disease. Hemophagocytosis is part of a sepsis-like clinical syndrome caused by hypercytokinemia due to a highly stimulated but ineffective immune response. Coagulopathy and hemorrhages, decreased white cell count, elevated levels of aspartate aminotransferase, fever, rash, hepatosplenomegaly and central nervous system dysfunction are some of diagnostic criteria of macrophage activation syndrome, but it is very difficult to diagnose due to the lack of specific clinical signs. We report a 8-year-old child who was admitted to the ICU with lethargy, fever, acute respiratory failure, coagulopathy, metabolic acidosis and multiorgan failure. Septic shock was suspected, but he was diagnosed with macrophage activation syndrome and treated with corticosteroids and intravenous immunoglobulin and later discharged from the ICU.

  14. High throughput estimation of functional cell activities reveals disease mechanisms and predicts relevant clinical outcomes.

    PubMed

    Hidalgo, Marta R; Cubuk, Cankut; Amadoz, Alicia; Salavert, Francisco; Carbonell-Caballero, José; Dopazo, Joaquin

    2017-01-17

    Understanding the aspects of the cell functionality that account for disease or drug action mechanisms is a main challenge for precision medicine. Here we propose a new method that models cell signaling using biological knowledge on signal transduction. The method recodes individual gene expression values (and/or gene mutations) into accurate measurements of changes in the activity of signaling circuits, which ultimately constitute high-throughput estimations of cell functionalities caused by gene activity within the pathway. Moreover, such estimations can be obtained either at cohort-level, in case/control comparisons, or personalized for individual patients. The accuracy of the method is demonstrated in an extensive analysis involving 5640 patients from 12 different cancer types. Circuit activity measurements not only have a high diagnostic value but also can be related to relevant disease outcomes such as survival, and can be used to assess therapeutic interventions.

  15. Serum platelet factor 4 is a reliable activity parameter in adult patients with inflammatory bowel disease

    PubMed Central

    Ye, Lei; Zhang, Yu-Ping; Yu, Na; Jia, Ya-Xu; Wan, Shu-Jun; Wang, Fang-Yu

    2017-01-01

    Abstract To investigate the diagnostic utility of serum platelet factor 4 (PF4) levels and to assess its accuracy in detecting inflammatory bowel disease activity. This study included 45 patients with ulcerative colitis (UC), 45 patients with Crohn disease (CD), and 30 control subjects at Jinling Hospital between May 2014 and July 2015. Laboratory tests measured white blood count, C-reactive protein, erythrocyte sedimentation rate, and platelet count. PF4 was examined by enzyme-linked immunosorbent assays. Patients were divided into 2 groups according to disease activity: active and inactive. Median PF4 values dramatically increased in UC and CD patients compared with the healthy group (UC: 26.64 [20.00–36.22] mg/mL vs 20.02 [14.63–26.83] mg/mL, P = 0.002; CD: 25.56 [18.57–36.36] mg/mL vs 20.02 [14.63–26.83] mg/mL, P = 0.014); however, the serum PF4 levels between UC and CD failed to show a significant difference (26.64 [20.00–36.22] mg/mL vs 25.56 [18.57–36.36] mg/mL, P = 0.521). Furthermore, serum PF4 levels were elevated in both UC and CD patients with active disease (UC: 20.19 [14.89–23.53] mg/mL vs 28.86 [22.57–37.29] mg/mL, P < 0.001; CD: 18.33 [16.72–25.77] mg/mL vs 34.38 [22.58–39.92] mg/mL, P < 0.001). Multivariate analysis revealed higher PF4 level as an independent predictor of disease activity in UC and CD patients (UC: odds ratio 30.375, P = 0.002; CD: odds ratio 54.167, P < 0.001). The cut-off level of PF4 for distinguishing active from inactive UC patients was 24.1 mg/mL. While in CD patients, the cut-off level of PF4 was 19.24 mg/mL. Serum PF4 levels could be a potential biomarker for monitoring the disease activity of inflammatory bowel disease. PMID:28296751

  16. A Descriptive Survey of Inflammatory Bowel Disease within the Active Army Population (1971-1982).

    DTIC Science & Technology

    1985-06-01

    DISEASE WITHIN THE ACTIVE ARMY POPULATATION (1971-1.982) 12. PERSONAL AUTHORS S MAJOR GEORGE M. GRASKI 13a. TYPE OF REPORT 13b. TIME COVERED 14...by Crohn and Ginsburg in 3 1932. The disease itself consists of an inflammatory condition of the bowel which extends through the gut to adjoining...No 1, June 1963, p. 14. S 1 0Vibeke Binder, "Incidence and Prevalence of Ulcerative Colitis and Crohn’s Disease in the County of Copenhagen, 1962 to

  17. Disease Mutations in Rab7 Result in Unregulated Nucleotide Exchange and Inappropriate Activation

    SciTech Connect

    B McCray; E Skordalakes; J Taylor

    2011-12-31

    Rab GTPases are molecular switches that orchestrate vesicular trafficking, maturation and fusion by cycling between an active, GTP-bound form, and an inactive, GDP-bound form. The activity cycle is coupled to GTP hydrolysis and is tightly controlled by regulatory proteins. Missense mutations of the GTPase Rab7 cause a dominantly inherited axonal degeneration known as Charcot-Marie-Tooth type 2B through an unknown mechanism. We present the 2.8 A crystal structure of GTP-bound L129F mutant Rab7 which reveals normal conformations of the effector binding regions and catalytic site, but an alteration to the nucleotide binding pocket that is predicted to alter GTP binding. Through extensive biochemical analysis, we demonstrate that disease-associated mutations in Rab7 do not lead to an intrinsic GTPase defect, but permit unregulated nucleotide exchange leading to both excessive activation and hydrolysis-independent inactivation. Consistent with augmented activity, mutant Rab7 shows significantly enhanced interaction with a subset of effector proteins. In addition, dynamic imaging demonstrates that mutant Rab7 is abnormally retained on target membranes. However, we show that the increased activation of mutant Rab7 is counterbalanced by unregulated, GTP hydrolysis-independent membrane cycling. Notably, disease mutations are able to rescue the membrane cycling of a GTPase-deficient mutant. Thus, we demonstrate that disease mutations uncouple Rab7 from the spatial and temporal control normally imposed by regulatory proteins and cause disease not by a gain of novel toxic function, but by misregulation of native Rab7 activity.

  18. Disease activity, quality of life, and indirect costs of ulcerative colitis in Poland

    PubMed Central

    Stawowczyk, Ewa; Mossakowska, Małgorzata; Pilc, Andrzej

    2017-01-01

    Introduction Ulcerative colitis (UC) require expensive, lifelong treatment, which generates huge direct costs and has a significant impact on the quality of life, especially in the active state of the disease. Aim To assess the indirect costs, health-related quality of life, and clinical characteristics of patients with UC in Poland. Additionally, we investigated the association between activity of UC and productivity loss of patients in a Polish setting. Material and methods A questionnaire survey was conducted using the Patient Simple Clinical Colitis Activity Index (P-SCCAI) to assess disease activity, as well as the modified Work Productivity and Activity Impairment Questionnaire to assess productivity loss. The quality of life was presented as utility calculated with the EQ-5D-3L questionnaire. Indirect costs were assessed with the Human Capital Approach and were expressed in Polish zlotys (PLN) as well as in euros (€). Correlations were presented using the Spearman coefficient. Results We performed our analysis based on 202 full questionnaires collected. Mean patient age and age at disease onset were 33.14 years (standard deviation (SD): 9.90) and 26.35 years (SD: 8.89), respectively. The mean P-SCCAI score in the analysed group of patients was 8.26, and the mean utility was 0.8651. Average and median annual indirect costs per working person were €2043 and €1389 (8543 PLN and 5808 PLN), respectively, calculated using the gross domestic product, as well as €4791 and €3257 (20,026 PLN and 13,615 PLN), respectively, calculated using the gross value added. Total productivity loss was significantly correlated with the disease activity. Conclusions Ulcerative colitis causes a decrease in the quality of life as well as patients’ productivity loss associated with both absenteeism and with presenteeism. PMID:28337239

  19. Bone erosions in rheumatoid arthritis can be repaired through reduction in disease activity with conventional disease-modifying antirheumatic drugs.

    PubMed

    Ideguchi, Haruko; Ohno, Shigeru; Hattori, Hideaki; Senuma, Akiko; Ishigatsubo, Yoshiaki

    2006-01-01

    We conducted the present study to determine whether repair of erosions occurs in patients with rheumatoid arthritis (RA) treated with conventional disease-modifying anti-rheumatic drugs (DMARDs) and to compare clinical characteristics between patients exhibiting and not exhibiting erosion repair. We included in the study a total of 122 RA patients who fulfilled the 1987 American College of Rheumatology criteria for RA; all patients had paired sequential radiographs of both hands and wrists showing erosive changes at baseline. Patients were classified into two groups according to the presence of repair of erosions at follow up, namely the 'repair observed' and 'repair not observed' groups. Clinical characteristics, disease activity, radiographic scores and treatment in the two groups were compared. Forty-four repairs were observed in 13 patients (10.7%). Compared with the repair not observed group, the functional class of the patients in the repair observed group was lower at baseline (P < 0.01) and the mean disease activity was lower at follow up (P < 0.005). The changes in radiographic scores per year (total radiographic score and erosion score) were lower (P < 0.05 and P < 0.01, respectively) in the repair observed group. No difference in treatment was observed. Repair of erosions was detected in 10.7% of RA patients treated with conventional DMARDs. Repairs were associated with low functional class at baseline and low disease activity at follow up. These observations support the importance of reduction in disease activity in RA patients. Because repair of erosions was detected in a substantial number of patients, assessment of erosion repair should be incorporated into the radiographic evaluation and scoring of RA.

  20. Antimicrobial Activity.

    PubMed

    2016-01-01

    Natural products of higher plants may possess a new source of antimicrobial agents with possibly novel mechanisms of action. They are effective in the treatment of infectious diseases while simultaneously mitigating many of the side effects that are often associated with conventional antimicrobials. A method using scanning electron microscope (SEM) to study the morphology of the bacterial and fungal microbes and thus determining antimicrobial activity is presented in the chapter.

  1. Engineering Neprilysin Activity and Specificity to Create a Novel Therapeutic for Alzheimer’s Disease

    PubMed Central

    Webster, Carl I.; Burrell, Matthew; Olsson, Lise-Lotte; Fowler, Susan B.; Digby, Sarah; Sandercock, Alan; Snijder, Arjan; Tebbe, Jan; Haupts, Ulrich; Grudzinska, Joanna; Jermutus, Lutz; Andersson, Christin

    2014-01-01

    Neprilysin is a transmembrane zinc metallopeptidase that degrades a wide range of peptide substrates. It has received attention as a potential therapy for Alzheimer’s disease due to its ability to degrade the peptide amyloid beta. However, its broad range of peptide substrates has the potential to limit its therapeutic use due to degradation of additional peptides substrates that tightly regulate many physiological processes. We sought to generate a soluble version of the ectodomain of neprilysin with improved activity and specificity towards amyloid beta as a potential therapeutic for Alzheimer’s disease. Extensive amino acid substitutions were performed at positions surrounding the active site and inner surface of the enzyme and variants screened for activity on amyloid beta 1–40, 1–42 and a variety of other physiologically relevant peptides. We identified several mutations that modulated and improved both enzyme selectivity and intrinsic activity. Neprilysin variant G399V/G714K displayed an approximately 20-fold improved activity on amyloid beta 1–40 and up to a 3,200-fold reduction in activity on other peptides. Along with the altered peptide substrate specificity, the mutant enzyme produced a markedly altered series of amyloid beta cleavage products compared to the wild-type enzyme. Crystallisation of the mutant enzyme revealed that the amino acid substitutions result in alteration of the shape and size of the pocket containing the active site compared to the wild-type enzyme. The mutant enzyme offers the potential for the more efficient degradation of amyloid beta in vivo as a therapeutic for the treatment of Alzheimer’s disease. PMID:25089527

  2. Stress system activity, innate and T helper cytokines, and susceptibility to immune-related diseases.

    PubMed

    Calcagni, Emanuele; Elenkov, Ilia

    2006-06-01

    Associations between stress and health outcomes have now been carefully documented, but the mechanisms by which stress specifically influences disease susceptibility and outcome remain poorly understood. Recent evidence indicates that glucocorticoids (GCs) and catecholamines (CAs), the major stress hormones, inhibit systemically IL-12, TNF-alpha, and INF-gamma, but upregulate IL-10, IL-4, and TGF-beta production. Thus, during an immune and inflammatory response, the activation of the stress system, through induction of a Th2 shift may protect the organism from systemic "overshooting" with T helper lymphocyte 1 (Th1)/proinflammatory cytokines. In certain local responses and under certain conditions, however, stress hormones may actually facilitate inflammation, through induction of IL-1, IL-6, IL-8, IL-18, TNF-alpha, and CRP production, and through activation of the corticotropin-releasing hormone (CRH)/substance P(SP)-histamine axis. Autoimmunity, chronic infections, major depression, and atherosclerosis are characterized by a dysregulation of the pro/anti-inflammatory and Th1/Th2 cytokine balance. Thus, hyperactive or hypoactive stress system, and a dysfunctional neuroendocrine-immune interface associated with abnormalities of the "systemic anti-inflammatory feedback" and/or "hyperactivity" of the local proinflammatory factors may contribute to the pathogenesis of these diseases. Conditions that are associated with significant changes in stress system activity, such as acute or chronic stress, cessation of chronic stress, pregnancy and the postpartum period, or rheumatoid arthritis (RA) through modulation of the systemic or local pro/anti-inflammatory and Th1/Th2 cytokine balance, may suppress or potentiate disease activity and/or progression. Thus, stress hormones-induced inhibition or upregulation of innate and Th cytokine production may represent an important mechanism by which stress affects disease susceptibility, activity, and outcome of various immune

  3. Impaired dual tasking in Parkinson's disease is associated with reduced focusing of cortico-striatal activity.

    PubMed

    Nieuwhof, Freek; Bloem, Bastiaan R; Reelick, Miriam F; Aarts, Esther; Maidan, Inbal; Mirelman, Anat; Hausdorff, Jeffrey M; Toni, Ivan; Helmich, Rick C

    2017-03-17

    Impaired dual tasking, namely the inability to concurrently perform a cognitive and a motor task (e.g. 'stops walking while talking'), is a largely unexplained and frequent symptom of Parkinson's disease. Here we consider two circuit-level accounts of how striatal dopamine depletion might lead to impaired dual tasking in patients with Parkinson's disease. First, the loss of segregation between striatal territories induced by dopamine depletion may lead to dysfunctional overlaps between the motor and cognitive processes usually implemented in parallel cortico-striatal circuits. Second, the known dorso-posterior to ventro-anterior gradient of dopamine depletion in patients with Parkinson's disease may cause a funnelling of motor and cognitive processes into the relatively spared ventro-anterior putamen, causing a neural bottleneck. Using functional magnetic resonance imaging, we measured brain activity in 19 patients with Parkinson's disease and 26 control subjects during performance of a motor task (auditory-cued ankle movements), a cognitive task (implementing a switch-stay rule), and both tasks simultaneously (dual task). The distribution of task-related activity respected the known segregation between motor and cognitive territories of the putamen in both groups, with motor-related responses in the dorso-posterior putamen and task switch-related responses in the ventro-anterior putamen. During dual task performance, patients made more motor and cognitive errors than control subjects. They recruited a striatal territory (ventro-posterior putamen) not engaged during either the cognitive or the motor task, nor used by controls. Relatively higher ventro-posterior putamen activity in controls was associated with worse dual task performance. These observations suggest that dual task impairments in Parkinson's disease are related to reduced spatial focusing of striatal activity. This pattern of striatal activity may be explained by a loss of functional segregation

  4. [Competitive sports and leisure-time physical activity in patients with coronary heart disease].

    PubMed

    Pedrinazzi, Claudio; Durin, Ornella; Inama, Giuseppe

    2012-10-01

    During recent years, the central role of exercise in the prevention of cardiovascular disease has gradually been demonstrated, and in 2003 the consensus document of the Council on Clinical Cardiology and Council on Nutrition, Physical Activity and Metabolism on the role of physical exercise in the prevention and treatment of coronary artery disease defined sedentary lifestyle as a modifiable independent cardiovascular risk factor, responsible for 12% of total mortality in the United States and for a 1.9-fold increase in the risk of ischemic heart disease. The reduction in cardiovascular mortality and cardiac ischemic events in subjects who perform regular physical activity is mainly due to the action that exercise plays on the control of cardiovascular risk factors. In particular, physical training has proved capable of improving lipid profile, reducing blood pressure and body weight, and improving glycemic control in diabetic subjects. In patients with coronary artery disease, combined exercise training, including both aerobic activities and strength training, is currently recommended. However, physical training in patients suffering from ischemic heart disease should be carefully prescribed, in order to maximize the positive effects and minimize the risks. It is also important that physical training programs are conducted in suitable facilities, with appropriately trained staff and with technical equipment suitable to deal with any emergency situations.

  5. Increased Enterococcus faecalis infection is associated with clinically active Crohn disease.

    PubMed

    Zhou, Youlian; Chen, Huiting; He, Hanchang; Du, Yanlei; Hu, Jiaqi; Li, Yingfei; Li, Yuyuan; Zhou, Yongjian; Wang, Hong; Chen, Ye; Nie, Yuqiang

    2016-09-01

    This study was performed to investigate the relationship between the abundance of pathogenic gut microbes in Chinese patients with inflammatory bowel disease (IBD) and disease severity.We collected clinical data and fecal samples from 47 therapy-naive Chinese patients with ulcerative colitis (UC), 67 patients with Crohn disease (CD), and 48 healthy volunteers. Bacteria levels of Fusobacterium species (spp), enterotoxigenic Bacteroides fragilis (B fragilis), enteropathogenic Escherichia coli (E coli), and Enterococcus faecalis (E faecalis) were assessed by quantitative real-time PCR (qRT-PCR). Spearman correlation coefficients were calculated to test associations between bacterial content and clinical parameters.Compared to healthy controls, the levels of both Fusobacterium spp and E faecalis were significantly increased in the feces of patients with IBD (P < 0.01). B fragilis levels were higher (P < 0.05) and E faecalis levels lower (P < 0.05) in patients with CD compared to those with UC. Increased E faecalis colonization in CD associated positively with disease activity (P = 0.015), Crohn disease activity index (CDAI; R = 0.3118, P = 0.0108), and fecal calprotectin (P = 0.016).E faecalis and Fusobacterium spp are significantly enriched in patients with IBD, and increased E faecalis infection is associated with clinically active CD.

  6. Increased Enterococcus faecalis infection is associated with clinically active Crohn disease

    PubMed Central

    Zhou, Youlian; Chen, Huiting; He, Hanchang; Du, Yanlei; Hu, Jiaqi; Li, Yingfei; Li, Yuyuan; Zhou, Yongjian; Wang, Hong; Chen, Ye; Nie, Yuqiang

    2016-01-01

    Abstract This study was performed to investigate the relationship between the abundance of pathogenic gut microbes in Chinese patients with inflammatory bowel disease (IBD) and disease severity. We collected clinical data and fecal samples from 47 therapy-naive Chinese patients with ulcerative colitis (UC), 67 patients with Crohn disease (CD), and 48 healthy volunteers. Bacteria levels of Fusobacterium species (spp), enterotoxigenic Bacteroides fragilis (B fragilis), enteropathogenic Escherichia coli (E coli), and Enterococcus faecalis (E faecalis) were assessed by quantitative real-time PCR (qRT-PCR). Spearman correlation coefficients were calculated to test associations between bacterial content and clinical parameters. Compared to healthy controls, the levels of both Fusobacterium spp and E faecalis were significantly increased in the feces of patients with IBD (P < 0.01). B fragilis levels were higher (P < 0.05) and E faecalis levels lower (P < 0.05) in patients with CD compared to those with UC. Increased E faecalis colonization in CD associated positively with disease activity (P = 0.015), Crohn disease activity index (CDAI; R = 0.3118, P = 0.0108), and fecal calprotectin (P = 0.016). E faecalis and Fusobacterium spp are significantly enriched in patients with IBD, and increased E faecalis infection is associated with clinically active CD. PMID:27684872

  7. Aortic ascorbic acid, trace elements, and superoxide dismutase activity in human aneurysmal and occlusive disease.

    PubMed

    Dubick, M A; Hunter, G C; Casey, S M; Keen, C L

    1987-02-01

    Altered trace elements and ascorbic acid metabolism have been implicated in the pathogenesis of atherosclerotic cardiovascular disease. However, their role in the disease process, or the effect of atherosclerosis on their tissue levels within plaque, is poorly understood. The present study analyzes the concentrations of Fe, Cu, Zn, and Mn, and ascorbic acid and superoxide dismutase (SOD) activity in tissue samples from 29 patients with abdominal aortic aneurysms (AAA) and 14 patients with atherosclerotic occlusive disease (AOD). It was observed that the Fe and Mn concentrations in AAA and AOD tissue were higher than the levels in nondiseased control aorta, whereas Cu and Zn levels in AAA and AOD tissue were similar to the levels in controls. The Zn:Cu ratio was significantly lower in the AAA tissue in comparison to both AOD and control tissue. In addition, AAA and AOD tissue had low ascorbic acid levels and low Cu,Zn-SOD activity with Cu,Zn-SOD:Mn-SOD ratios of 0.27 and 0.19, respectively, compared to a ratio of 3.20 in control aorta. These data indicate that aorta affected by aneurysms and occlusive disease have altered trace element and ascorbic acid concentrations, as well as low Cu,Zn-SOD activity. Although these observations do not directly support the hypothesis that AAA is associated with aortic Cu deficiency they do suggest a role for oxygen radicals or increased lipid peroxidation in occlusive and aneurysmal disease of the aorta.

  8. Aortic ascorbic acid, trace elements, and superoxide dismutase activity in human aneurysmal and occlusive disease

    SciTech Connect

    Dubick, M.A.; Hunter, G.C.; Casey, S.M.; Keen, C.L.

    1987-02-01

    Altered trace elements and ascorbic acid metabolism have been implicated in the pathogenesis of atherosclerotic cardiovascular disease. However, their role in the disease process, or the effect of atherosclerosis on their tissue levels within plaque, is poorly understood. The presence study analyzes the concentrations of Fe, Cu, Zn, and Mn, and ascorbic acid and superoxide dismutase (SOD) activity in tissue samples from 29 patients with abdominal aortic aneurysms (AAA) and 14 patients with atherosclerotic occlusive disease (AOD). It was observed that the Fe and Mn concentrations in AAA and AOD tissue were higher than the levels in nondiseased control aorta, whereas Cu and Zn levels in AAA and AOD tissue were similar to the levels in controls. The Zn:Cu ratio was significantly lower in the AAA tissue in comparison to both AOD and control tissue. In addition, AAA and AOD tissue had low ascorbic acid levels and low Cu, Zn-SOD activity with Cu,Zn-SOD:Mn-SOD ratios of 0.27 and 0.19, respectively, compared to a ratio of 3.20 in control aorta. These data indicate that aorta affected by aneurysms and occlusive disease have altered trace element and ascorbic acid concentrations, as well as low Cu,Zn-SOD activity. Although these observations do not directly support the hypothesis that AAA is associated with aortic Cu deficiency they do suggest a role for oxygen radicals or increased lipid peroxidation in occlusive and aneurysmal disease of the aorta.

  9. Treatment with tumour necrosis factor inhibitor oxpentifylline does not improve corticosteroid dependent chronic active Crohn's disease.

    PubMed Central

    Bauditz, J; Haemling, J; Ortner, M; Lochs, H; Raedler, A; Schreiber, S

    1997-01-01

    BACKGROUND: In Crohn's disease, inflammation is presumably sustained by an increased production of proinflammatory cytokines, in particular tumour necrosis factor alpha (TNF alpha) and interleukin 1 beta (IL 1 beta). TNF alpha can induce a host of cellular effector events resulting in perpetuation of the inflammatory process. In vivo studies with anti-TNF alpha antibody treatment have led to impressive clinical results. AIMS: To investigate whether treatment with the TNF alpha inhibitor oxpentifylline results in clinical improvement in corticosteroid dependent chronic active Crohn's disease. METHODS: Sixteen Crohn's disease patients received oxpentifylline 400 mg four times a day in a four week open label study. RESULTS: Blockade of TNF alpha production in 16 patients with corticosteroid dependent Crohn's disease did not improve the clinical disease activity (CDAI mean (SEM) 188.75 (5.65) versus 185.13 (10.87) or the endoscopic degree of inflammation (CDEIS 14.9 (2.87) versus 14.8 (2.27) or laboratory parameters. CONCLUSIONS: In this study, use of the TNF alpha inhibitor oxpentifylline does not improve inflammation in Crohn's disease. This finding suggests that there may be more key mediators than only TNF alpha in the inflammatory process in Crohn's disease. PMID:9176073

  10. The pharmacological mechanisms and therapeutic activities of hydroxychloroquine in rheumatic and related diseases.

    PubMed

    Hu, Changfeng; Lu, Lu; Wan, Jie-Ping; Wen, Chengping

    2017-03-16

    Hydroxychloroquine (HCQ) is known as one of the most fascinating synthetic antimalarial drugs during the last 50 years. It is currently among the most commonly employed medicines for the clinical treatment of rheumatic diseases, especially systemic lupus erythematosus and rheumatoid arthritis. In related mechanism studies, it has been found that HCQ possesses various immunomodulatory and anti-inflammatory activities. In addition, the effects of HCQ on anti-platelet, metabolic pathways, and antineoplasticity have also been disclosed in more recent studies. These significant findings on HCQ suggest the potential therapeutic applications of HCQ for treatment of many diseases, such as cancers, skin disease, antiphospholipid syndrome, etc. This review focuses on recent in vitro and clinical trials on its pharmacological mechanisms, therapeutic activities, and potential adverse effects.

  11. [Physical activity for prevention and therapy of internal diseases in the elderly].

    PubMed

    Weisser, Burkhard; Preuss, Manuela; Predel, Hans-Georg

    2009-04-15

    There is a growing number of elderly people in Western societies. Therefore, the prevalence of age-associated diseases increases. For most of these conditions, exercise and physical activity play a major role in the prevention and therapy. However, it is well established that the level of physical activity is lowest in elderly people. Physical fitness continues to be the most important protective health factor and should be improved in the elderly population. Many exercise recommendations include only endurance programs, but strength and coordination also deliver positive therapeutic effects in cardiovascular and metabolic diseases, lung diseases, neoplasms, and many other pathologic conditions including dementia. Age-specific recommendations should be included in exercise programs for health.

  12. The impact of microglial activation on blood-brain barrier in brain diseases

    PubMed Central

    da Fonseca, Anna Carolina Carvalho; Matias, Diana; Garcia, Celina; Amaral, Rackele; Geraldo, Luiz Henrique; Freitas, Catarina; Lima, Flavia Regina Souza

    2014-01-01

    The blood-brain barrier (BBB), constituted by an extensive network of endothelial cells (ECs) together with neurons and glial cells, including microglia, forms the neurovascular unit (NVU). The crosstalk between these cells guarantees a proper environment for brain function. In this context, changes in the endothelium-microglia interactions are associated with a variety of inflammation-related diseases in brain, where BBB permeability is compromised. Increasing evidences indicate that activated microglia modulate expression of tight junctions, which are essential for BBB integrity and function. On the other hand, the endothelium can regulate the state of microglial activation. Here, we review recent advances that provide insights into interactions between the microglia and the vascular system in brain diseases such as infectious/inflammatory diseases, epilepsy, ischemic stroke and neurodegenerative disorders. PMID:25404894

  13. Role of Peroxisome Proliferator-Activated Receptor γ in Ocular Diseases

    PubMed Central

    Zhang, Su; Gu, Hongwei; Hu, Nan

    2015-01-01

    Peroxisome proliferator-activated receptor γ (PPAR γ), a member of the nuclear receptor superfamily, is a ligand-activated transcription factor that plays an important role in the control of a variety of physiological processes. The last decade has witnessed an increasing interest for the role played by the agonists of PPAR γ in antiangiogenesis, antifibrosis, anti-inflammation effects and in controlling oxidative stress response in various organs. As the pathologic mechanisms of major blinding diseases, such as age-related macular degeneration (AMD), diabetic retinopathy (DR), keratitis, and optic neuropathy, often involve neoangiogenesis and inflammation- and oxidative stress-mediated cell death, evidences are accumulating on the potential benefits of PPAR γ to improve or prevent these vision threatening eye diseases. In this paper we describe what is known about the role of PPAR γ in the ocular pathophysiological processes and PPAR γ agonists as novel adjuvants in the treatment of eye diseases. PMID:26146566

  14. Chitotriosidase Activity and Gene Polymorphism in Iranian Patients with Gaucher Disease and Sibling Carriers

    PubMed Central

    MOZAFARI, Hadi; TAGHIKHANI, Mohammad; KHATAMI, Shohreh; ALAEI, Mohammad Reza; VAISI-RAYGANI, Asad; RAHIMI, Zohreh

    2016-01-01

    Objective Chitotriosidase (CT) activity is a useful biomarker for diagnosis and monitoring of Gaucher disease (GD). Its application is limited by some variants in the CT gene. Two main polymorphisms are 24 bp duplication and G102S led to reduce CT activity. The aim of this study was to determine these variants influencing on plasma CT activity. Materials & Methods Blood samples were collected from 33 patients with GD, 15 sibling carriers and 105 healthy individuals serving as controls. CT activity was measured using 4-methylumbelliferyl-β-D-N,N′,N″triacetylchitotrioside substrate in plasma samples. The CT genotypes of 24 bp duplication and G102S variants were determined using PCR and PCR-RFLP. Results Untreated GD patients had a significantly higher CT activity compared to treated patients (P = 0.021). In addition, chitotriosidase activity in carriers was higher rather than controls. Allele frequencies of 24 bp duplication in GD patients, sibling carriers and controls were 0.21, 0.266 and 0.29 and for G102S were 0.318, 0.366 and 0.219, respectively. Different G102S genotypes had not significant effect on CT activity. Chitotriosidase activity has a positive correlation with age in normal group, carriers, and negative correlation with hemoglobin in GD patients. Using cut-off level of 80.75 nmol/ml/h, sensitivity and specificity of CT activity were 93.9% and 100%, respectively. Conclusion Chitotriosidase activity is a suitable biomarker for diagnosis and monitoring of GD. Determination of 24 bp duplication is helpful for more accurate monitoring the GD patient’s therapy. However, it seems that, specifying of the G102S polymorphism is not required for Iranian GD patients. PMID:27843468

  15. Relation of physical activity to cardiovascular disease mortality and the influence of cardiometabolic risk factors.

    PubMed

    Reddigan, Jacinta I; Ardern, Chris I; Riddell, Michael C; Kuk, Jennifer L

    2011-11-15

    Physical activity can improve several metabolic risk factors associated with cardiovascular disease (CVD) and is associated with a lower risk of CVD mortality. We sought to evaluate the extent to which metabolic risk factors mediate the association between physical activity and CVD mortality and whether physical activity provides protective effects against CVD mortality in healthy adults and those with metabolic risk factors. A sample of 10,261 adults from the Third National Health and Nutrition Examination Survey with public-access mortality data linkage (follow-up 13.4 ± 3.9 years) was used. Physical activity was assessed by questionnaire and classified into inactive, light, and moderate/vigorous activity categories. Metabolic risk factors (dyslipidemia, type 2 diabetes mellitus, obesity, hypertension, inflammation, and insulin resistance) were categorized using clinical thresholds. After adjusting for basic confounders, engaging in light or moderate/vigorous physical activity was associated with a lower risk of CVD mortality (p < 0.05). Adjustment for each risk-factor set only slightly attenuated this relation. When all risk-factor sets were added to the model simultaneously, light (hazard ratio 0.72, 0.62 to 0.84) and moderate/vigorous (hazard ratio 0.72, 0.62 to 0.85) activity remained at lower risk of CVD mortality. In addition, physical activity provided protective effects for CVD mortality in healthy subjects and those with metabolic risk factors in isolation or in clusters. In conclusion, physical activity was associated with a lower risk of CVD mortality independent of traditional and inflammatory risk factors. Taken together these results suggest that physical activity may protect against CVD mortality regardless of the presence of metabolic risk factors.

  16. Behçet’s disease: new insight into the relationship between procoagulant state, endothelial activation/damage and disease activity

    PubMed Central

    2013-01-01

    Background Behçet disease (BD) is associated with a prothrombotic state of unknown origin that may lead to life-threatening events. Calibrated Automated Thrombogram (CAT) and Rotational Thromboelastometry (ROTEM) are two global haemostasis assays that may reveal new insights into the physiopathological mechanisms of the disease and its procoagulant condition. Methods 23 BD patients who had no signs or symptoms of current thrombosis and 33 age- and sex-matched controls were included in the study. We performed ROTEM and CAT tests and assessed erythrocyte count, platelet count, platelet contribution to clot formation and plasma levels of tissue-type plasminogen activator, plasminogen activator inhibitor type 1 (PAI-1), fibrinogen, C-reactive protein (CRP), thrombin-antithrombin III complex (TAT), D-dimer and E-selectin (ES). Results Both ROTEM and CAT tests showed a hypercoagulable state in the BD patients. Plasma levels of PAI-1, fibrinogen, TAT, CRP and ES were significantly increased in this group compared to controls. The disease activity (DA) was significantly correlated with levels of ES and the maximum clot firmness, and this last one, in turn, correlated with rising levels of ES, PAI-1, CRP and fibrinogen. CAT parameters did not correlate with DA or ES. Conclusions Both ROTEM and CAT tests reveal that patients with BD have a procoagulant state even in the absence of thrombosis. ROTEM test indicates that increased levels of fibrinogen and PAI-1 may be involved in the prothrombotic state of this pathology, while platelets do not significantly contribute. Moreover, CAT assay demonstrate that plasma from BD patients is able to generate more thrombin than controls in response to the same stimulus and that this effect is independent of the DA and the endothelial impairment suggesting the involvement of another factor in the hypercoagulable state observed in BD patients. This study also shows that endothelium activation/damage may be a contributing factor in both

  17. Human Tissue Kallikrein Activity in Angiographically Documented Chronic Stable Coronary Artery Disease

    PubMed Central

    Figueiredo, Estêvão Lanna; Magalhães, Carolina Antunes; Belli, Karlyse Claudino; Mandil, Ari; Garcia, José Carlos Faria; Araújo, Rosanã Aparecida; Figueiredo, Amintas Fabiano de Souza; Pellanda, Lucia Campos

    2015-01-01

    Background Human tissue kallikrein (hK1) is a key enzyme in the kallikrein–kinin system (KKS). hK1-specific amidase activity is reduced in urine samples from hypertensive and heart failure (HF) patients. The pathophysiologic role of hK1 in coronary artery disease (CAD) remains unclear. Objective To evaluate hK1-specific amidase activity in the urine of CAD patients Methods Sixty-five individuals (18–75 years) who underwent cardiac catheterism (CATH) were included. Random midstream urine samples were collected immediately before CATH. Patients were classified in two groups according to the presence of coronary lesions: CAD (43 patients) and non-CAD (22 patients). hK1 amidase activity was estimated using the chromogenic substrate D-Val-Leu-Arg-Nan. Creatinine was determined using Jaffé’s method. Urinary hK1-specific amidase activity was expressed as µM/(min · mg creatinine) to correct for differences in urine flow rates. Results Urinary hK1-specific amidase activity levels were similar between CAD [0.146 µM/(min ·mg creatinine)] and non-CAD [0.189 µM/(min . mg creatinine)] patients (p = 0.803) and remained similar to values previously reported for hypertensive patients [0.210 µM/(min . mg creatinine)] and HF patients [0.104 µM/(min . mg creatinine)]. CAD severity and hypertension were not observed to significantly affect urinary hK1-specific amidase activity. Conclusion CAD patients had low levels of urinary hK1-specific amidase activity, suggesting that renal KKS activity may be reduced in patients with this disease. PMID:26351984

  18. No differences of butyrylcholinesterase protein activity and allele frequency in Lewy body diseases.

    PubMed

    Maetzler, Walter; Keller, Stefanie; Michelis, Joan; Koehler, Niklas; Stransky, Elke; Becker, Clemens; Schulte, Claudia; Melms, Arthur; Gasser, Thomas; Berg, Daniela

    2009-08-01

    Butyrylcholinesterase (BChE) genotypes and protein (BuChE) activity, especially in combination with Apolipoprotein E4 (ApoE4), have been investigated as risk factors for developing Alzheimer disease (AD) and may be associated with the rate of progression of cognitive decline. Despite similar pathologic (e.g. amyloid deposition) and neurochemical (e.g. cholinergic deficits) aspects between AD and Lewy body diseases (LBD), scarce data is obtainable about BChE genotypes and BuChE activity in LBD. We measured BuChE activity levels in serum and cerebrospinal fluid (CSF) of 114 LBD subjects (59 of them were demented) and 31 elderly controls. We found higher CSF BuChE activity in males compared to females, and a negative correlation of serum BuChE activity with age and cognitive function. Demented LBD patients, non-demented LBD patients and controls did not differ significantly with regard to serum and CSF BuChE activity. Furthermore, BChE K variant and ApoE4 allele frequencies were determined. The BChE K variant was significantly associated with lower serum activity; the same trend was observable in CSF. The subgroups did not differ significantly with regard to BChE K/ApoE4 occurrence. These data confirm and extend previous results on the relationship between BChE gene and BuChE activity, and argue rather against a major impact of BuChE on LBD-associated pathologies.

  19. Longitudinal influence of microglial activation and amyloid on neuronal function in Alzheimer's disease.

    PubMed

    Fan, Zhen; Okello, Aren A; Brooks, David J; Edison, Paul

    2015-12-01

    Amyloid deposition, tangle formation, neuroinflammation and neuronal dysfunction are pathological processes involved in Alzheimer's disease. However, the relative role of these processes in driving disease progression is still unclear. The aim of this positron emission tomography study was to: (i) investigate longitudinal changes of microglial activation, amyloid and glucose metabolism; and (ii) assess the temporospatial relationship between these three processes in Alzheimer's disease. A group of eight patients with a diagnosis of Alzheimer's disease (66 ± 4.8 years) and 14 healthy controls (65 ± 5.5 years) underwent T1 and T2 magnetic resonance imaging, along with (11)C-(R)-PK11195, (11)C-Pittsburgh compound B and (18)F-fluorodeoxyglucose positron emission tomography scans for microglial activation, amyloid deposition and glucose metabolism. All patients were followed-up with repeated magnetic resonance imaging and three positron emission tomography scans after 16 months. Parametric maps were interrogated using region of interest analysis, Statistical Parametric Mapping, and between-group correlation analysis at voxel-level using Biological Parametric Mapping. At baseline, patients with Alzheimer's disease showed significantly increased microglial activation compared to the control subjects. During follow-up, for the first time, we found that while there is a progressive reduction of glucose metabolism, there was a longitudinal increase of microglial activation in the majority of the patients with Alzheimer's disease. Voxel-wise correlation analysis revealed that microglial activation in patients with Alzheimer's disease was positively correlated with amyloid deposition and inversely correlated with regional cerebral metabolic rate at voxel level over time. Even though one of the limitations of this study is the lack of longitudinal follow-up of healthy control subjects, this study demonstrates that there is persistent neuroinflammation throughout the Alzheimer

  20. Blood cell superoxide dismutase and enolase activities as markers of alcoholic and nonalcoholic liver diseases.

    PubMed

    Ledig, M; Doffoel, M; Doffoel, S; Kopp, P; Bockel, R; Mandel, P

    1988-01-01

    Monitoring of chronic alcoholism would be facilitated by using sensitive biochemical markers in blood cells, mainly to detect differences between alcoholic subjects with or without liver injury. We propose two types of markers: the first one is superoxide dismutase (SOD) activity involved in the conversion of superoxide radicals (O2-.) formed during acetaldehyde oxidation by xanthine oxidase after chronic alcohol consumption; the second one is enolase activity with both isoenzyme forms: nonneuronal enolase (NNE) and neuron specific enolase (NSE) which has been shown to be modified in many injuries related to the glycolytic pathways. For SOD activity we found a significant increase in alcoholic patients with liver injury and mainly in cirrhotic patients with ascitis. Both enolase activities were also found to be significantly increased in alcoholic patients with liver injury but NNE activity was also increased in alcoholics without apparent liver disease. Our results suggest that increased activity of SOD and NSE in blood cells may be related to liver injury mainly in alcoholism while increased NNE activity may also be a marker of alcohol abuse without liver injury.

  1. Nonlinear analysis of human physical activity patterns in health and disease

    NASA Astrophysics Data System (ADS)

    Paraschiv-Ionescu, A.; Buchser, E.; Rutschmann, B.; Aminian, K.

    2008-02-01

    The reliable and objective assessment of chronic disease state has been and still is a very significant challenge in clinical medicine. An essential feature of human behavior related to the health status, the functional capacity, and the quality of life is the physical activity during daily life. A common way to assess physical activity is to measure the quantity of body movement. Since human activity is controlled by various factors both extrinsic and intrinsic to the body, quantitative parameters only provide a partial assessment and do not allow for a clear distinction between normal and abnormal activity. In this paper, we propose a methodology for the analysis of human activity pattern based on the definition of different physical activity time series with the appropriate analysis methods. The temporal pattern of postures, movements, and transitions between postures was quantified using fractal analysis and symbolic dynamics statistics. The derived nonlinear metrics were able to discriminate patterns of daily activity generated from healthy and chronic pain states.

  2. PERK activation preserves the viability and function of remyelinating oligodendrocytes in immune-mediated demyelinating diseases.

    PubMed

    Lin, Yifeng; Huang, Guangcun; Jamison, Stephanie; Li, Jin; Harding, Heather P; Ron, David; Lin, Wensheng

    2014-02-01

    Remyelination occurs in multiple sclerosis (MS) lesions but is generally considered to be insufficient. One of the major challenges in MS research is to understand the causes of remyelination failure and to identify therapeutic targets that promote remyelination. Activation of pancreatic endoplasmic reticulum kinase (PERK) signaling in response to endoplasmic reticulum stress modulates cell viability and function under stressful conditions. There is evidence that PERK is activated in remyelinating oligodendrocytes in demyelinated lesions in both MS and its animal model, experimental autoimmune encephalomyelitis (EAE). In this study, we sought to determine the role of PERK signaling in remyelinating oligodendrocytes in MS and EAE using transgenic mice that allow temporally controlled activation of PERK signaling specifically in oligodendrocytes. We demonstrated that persistent PERK activation was not deleterious to myelinating oligodendrocytes in young, developing mice or to remyelinating oligodendrocytes in cuprizone-induced demyelinated lesions. We found that enhancing PERK activation, specifically in (re)myelinating oligodendrocytes, protected the cells and myelin against the detrimental effects of interferon-γ, a key proinflammatory cytokine in MS and EAE. More important, we showed that enhancing PERK activation in remyelinating oligodendrocytes at the recovery stage of EAE promoted cell survival and remyelination in EAE demyelinated lesions. Thus, our data provide direct evidence that PERK activation cell-autonomously enhances the survival and preserves function of remyelinating oligodendrocytes in immune-mediated demyelinating diseases.

  3. 3-Hydroxyanthranilate oxygenase activity is increased in the brains of Huntington disease victims.

    PubMed Central

    Schwarcz, R; Okuno, E; White, R J; Bird, E D; Whetsell, W O

    1988-01-01

    An excess of the tryptophan metabolite quinolinic acid in the brain has been hypothetically related to the pathogenesis of Huntington disease. Quinolinate's immediate biosynthetic enzyme, 3-hydroxyanthranilate oxygenase (EC 1.13.11.6), has now been detected in human brain tissue. The activity of 3-hydroxyanthranilate oxygenase is increased in Huntington disease brains as compared to control brains. The increment is particularly pronounced in the striatum, which is known to exhibit the most prominent nerve-cell loss in Huntington disease. Thus, the Huntington disease brain has a disproportionately high capability to produce the endogenous "excitotoxin" quinolinic acid. This finding may be of relevance for clinical, neuropathologic, and biochemical features associated with Huntington disease. PMID:2967497

  4. Parasite biomass-related inflammation, endothelial activation, microvascular dysfunction and disease severity in vivax malaria.

    PubMed

    Barber, Bridget E; William, Timothy; Grigg, Matthew J; Parameswaran, Uma; Piera, Kim A; Price, Ric N; Yeo, Tsin W; Anstey, Nicholas M

    2015-01-01

    Plasmodium vivax can cause severe malaria, however its pathogenesis is poorly understood. In contrast to P. falciparum, circulating vivax parasitemia is low, with minimal apparent sequestration in endothelium-lined microvasculature, and pathogenesis thought unrelated to parasite biomass. However, the relationships between vivax disease-severity and total parasite biomass, endothelial autocrine activation and microvascular dysfunction are unknown. We measured circulating parasitemia and markers of total parasite biomass (plasma parasite lactate dehydrogenase [pLDH] and PvLDH) in adults with severe (n = 9) and non-severe (n = 53) vivax malaria, and examined relationships with disease-severity, endothelial activation, and microvascular function. Healthy controls and adults with non-severe and severe falciparum malaria were enrolled for comparison. Median peripheral parasitemia, PvLDH and pLDH were 2.4-fold, 3.7-fold and 6.9-fold higher in severe compared to non-severe vivax malaria (p = 0.02, p = 0.02 and p = 0.015, respectively), suggesting that, as in falciparum malaria, peripheral P. vivax parasitemia underestimates total parasite biomass, particularly in severe disease. P. vivax schizonts were under-represented in peripheral blood. Severe vivax malaria was associated with increased angiopoietin-2 and impaired microvascular reactivity. Peripheral vivax parasitemia correlated with endothelial activation (angiopoietin-2, von-Willebrand-Factor [VWF], E-selectin), whereas markers of total vivax biomass correlated only with systemic inflammation (IL-6, IL-10). Activity of the VWF-cleaving-protease, ADAMTS13, was deficient in proportion to endothelial activation, IL-6, thrombocytopenia and vivax disease-severity, and associated with impaired microvascular reactivity in severe disease. Impaired microvascular reactivity correlated with lactate in severe vivax malaria. Findings suggest that tissue accumulation of P. vivax may occur, with the hidden

  5. Parasite Biomass-Related Inflammation, Endothelial Activation, Microvascular Dysfunction and Disease Severity in Vivax Malaria

    PubMed Central

    Barber, Bridget E.; William, Timothy; Grigg, Matthew J.; Parameswaran, Uma; Piera, Kim A.; Price, Ric N.; Yeo, Tsin W.; Anstey, Nicholas M.

    2015-01-01

    Plasmodium vivax can cause severe malaria, however its pathogenesis is poorly understood. In contrast to P. falciparum, circulating vivax parasitemia is low, with minimal apparent sequestration in endothelium-lined microvasculature, and pathogenesis thought unrelated to parasite biomass. However, the relationships between vivax disease-severity and total parasite biomass, endothelial autocrine activation and microvascular dysfunction are unknown. We measured circulating parasitemia and markers of total parasite biomass (plasma parasite lactate dehydrogenase [pLDH] and PvLDH) in adults with severe (n = 9) and non-severe (n = 53) vivax malaria, and examined relationships with disease-severity, endothelial activation, and microvascular function. Healthy controls and adults with non-severe and severe falciparum malaria were enrolled for comparison. Median peripheral parasitemia, PvLDH and pLDH were 2.4-fold, 3.7-fold and 6.9-fold higher in severe compared to non-severe vivax malaria (p = 0.02, p = 0.02 and p = 0.015, respectively), suggesting that, as in falciparum malaria, peripheral P. vivax parasitemia underestimates total parasite biomass, particularly in severe disease. P. vivax schizonts were under-represented in peripheral blood. Severe vivax malaria was associated with increased angiopoietin-2 and impaired microvascular reactivity. Peripheral vivax parasitemia correlated with endothelial activation (angiopoietin-2, von-Willebrand-Factor [VWF], E-selectin), whereas markers of total vivax biomass correlated only with systemic inflammation (IL-6, IL-10). Activity of the VWF-cleaving-protease, ADAMTS13, was deficient in proportion to endothelial activation, IL-6, thrombocytopenia and vivax disease-severity, and associated with impaired microvascular reactivity in severe disease. Impaired microvascular reactivity correlated with lactate in severe vivax malaria. Findings suggest that tissue accumulation of P. vivax may occur, with the hidden

  6. EMG activity and neuronal activity in the internal globus pallidus (GPi) and their interaction are different between hemiballismus and apomorphine induced dyskinesias of Parkinson's disease (AID).

    PubMed

    Zhao, L; Verhagen-Metman, L; Kim, J H; Liu, C C; Lenz, F A

    2015-04-07

    The nature of electromyogram (EMG) activity and its relationship to neuronal activity in the internal globus pallidus (GPi) have not previously been studied in hyperkinetic movement disorders. We now test the hypothesis that GPi spike trains are cross-correlated with EMG activity during apomorphine-induced dyskinesias of Parkinson's disease (AID), and Hemiballism. We have recorded these two signals during awake stereotactic pallidal surgeries and analyzed them by cross-correlation of the raw signals and of peaks of activity occurring in those signals. EMG signals in Hemiballism usually consist of 'sharp' activity characterized by peaks of activity with low levels of activity between peaks, and by co-contraction between antagonistic muscles. Less commonly, EMG in Hemiballism shows 'non-sharp' EMG activity with substantial EMG activity between peaks; 'non-sharp' EMG activity is more common in AID. Therefore, these hyperkinetic disorders show substantial differences in peripheral (EMG) activity, although both kinds of activity can occur in both disorders. Since GPi spike×EMG spectral and time domain functions demonstrated inconsistent cross-correlation in both disorders, we studied peaks of activity in GPi neuronal and in EMG signals. The peaks of GPi activity commonly show prolonged cross-correlation with peaks of EMG activity, which suggests that GPi peaks are related to the occurrence of EMG peaks, perhaps by transmission of GPi activity to the periphery. In Hemiballism, the presence of direct GPi peak×EMG peak cross-correlations at the site where lesions relieve these disorders is evidence that gradual changes in peak GPi neuronal activity are directly involved in Hemiballism.

  7. Microglial activation in regions related to cognitive function predicts disease onset in Huntington's disease: a multimodal imaging study.

    PubMed

    Politis, Marios; Pavese, Nicola; Tai, Yen F; Kiferle, Lorenzo; Mason, Sarah L; Brooks, David J; Tabrizi, Sarah J; Barker, Roger A; Piccini, Paola

    2011-02-01

    Huntington's disease (HD) is an inherited neurodegenerative disorder associated with motor, cognitive and psychiatric deficits. This study, using a multimodal imaging approach, aims to assess in vivo the functional and structural integrity of regions and regional networks linked with motor, cognitive and psychiatric function. Predicting disease onset in at risk individuals is problematic and thus we sought to investigate this by computing the 5-year probability of HD onset (p5 HD) and relating it to imaging parameters. Using MRI, (11)C-PK11195 and (11)C-raclopride PET, we have investigated volumes, levels of microglial activation and D2/D3 receptor binding in CAG repeat-matched groups of premanifest and symptomatic HD gene carriers. Findings were correlated with disease-burden and UHDRS scores. Atrophy was detected in sensorimotor striatum (SMST), substantia nigra, orbitofrontal and anterior prefrontal cortex in the premanifest HD. D2/D3 receptor binding was reduced and microglial activation increased in SMST and associative striatum (AST), bed nucleus of the stria terminalis, the amygdala and the hypothalamus. In symptomatic HD cases this extended to involve atrophy in globus pallidus, limbic striatum, the red nuclei, anterior cingulate cortex, and insula. D2/D3 receptor binding was additionally reduced in substantia nigra, globus pallidus, limbic striatum, anterior cingulate cortex and insula, and microglial activation increased in globus pallidus, limbic striatum and anterior prefrontal cortex. In premanifest HD, increased levels of microglial activation in the AST and in the regional network associated with cognitive function correlated with p5 HD onset. These data suggest that pathologically activated microglia in AST and other areas related to cognitive function, maybe better predictors of clinical onset and stresses the importance of early cognitive assessment in HD.

  8. Antibacterial Activity of Marine and Black Band Disease Cyanobacteria against Coral-Associated Bacteria

    PubMed Central

    Gantar, Miroslav; Kaczmarsky, Longin T.; Stanić, Dina; Miller, Aaron W.; Richardson, Laurie L.

    2011-01-01

    Black band disease (BBD) of corals is a cyanobacteria-dominated polymicrobial disease that contains diverse populations of heterotrophic bacteria. It is one of the most destructive of coral diseases and is found globally on tropical and sub-tropical reefs. We assessed ten strains of BBD cyanobacteria, and ten strains of cyanobacteria isolated from other marine sources, for their antibacterial effect on growth of heterotrophic bacteria isolated from BBD, from the surface mucopolysaccharide layer (SML) of healthy corals, and three known bacterial coral pathogens. Assays were conducted using two methods: co-cultivation of cyanobacterial and bacterial isolates, and exposure of test bacteria to (hydrophilic and lipophilic) cyanobacterial cell extracts. During co-cultivation, 15 of the 20 cyanobacterial strains tested had antibacterial activity against at least one of the test bacterial strains. Inhibition was significantly higher for BBD cyanobacteria when compared to other marine cyanobacteria. Lipophilic extracts were more active than co-cultivation (extracts of 18 of the 20 strains were active) while hydrophilic extracts had very limited activity. In some cases co-cultivation resulted in stimulation of BBD and SML bacterial growth. Our results suggest that BBD cyanobacteria are involved in structuring the complex polymicrobial BBD microbial community by production of antimicrobial compounds. PMID:22073011

  9. Sustained CTL activation by murine pulmonary epithelial cells promotes the development of COPD-like disease

    PubMed Central

    Borchers, Michael T.; Wesselkamper, Scott C.; Curull, Victor; Ramirez-Sarmiento, Alba; Sánchez-Font, Albert; Garcia-Aymerich, Judith; Coronell, Carlos; Lloreta, Josep; Agusti, Alvar G.; Gea, Joaquim; Howington, John A.; Reed, Michael F.; Starnes, Sandra L.; Harris, Nathaniel L.; Vitucci, Mark; Eppert, Bryan L.; Motz, Gregory T.; Fogel, Kevin; McGraw, Dennis W.; Tichelaar, Jay W.; Orozco-Levi, Mauricio

    2009-01-01

    Chronic obstructive pulmonary disease (COPD) is a lethal progressive lung disease culminating in permanent airway obstruction and alveolar enlargement. Previous studies suggest CTL involvement in COPD progression; however, their precise role remains unknown. Here, we investigated whether the CTL activation receptor NK cell group 2D (NKG2D) contributes to the development of COPD. Using primary murine lung epithelium isolated from mice chronically exposed to cigarette smoke and cultured epithelial cells exposed to cigarette smoke extract in vitro, we demonstrated induced expression of the NKG2D ligand retinoic acid early transcript 1 (RAET1) as well as NKG2D-mediated cytotoxicity. Furthermore, a genetic model of inducible RAET1 expression on mouse pulmonary epithelial cells yielded a severe emphysematous phenotype characterized by epithelial apoptosis and increased CTL activation, which was reversed by blocking NKG2D activation. We also assessed whether NKG2D ligand expression corresponded with pulmonary disease in human patients by staining airway and peripheral lung tissues from never smokers, smokers with normal lung function, and current and former smokers with COPD. NKG2D ligand expression was independent of NKG2D receptor expression in COPD patients, demonstrating that ligand expression is the limiting factor in CTL activation. These results demonstrate that aberrant, persistent NKG2D ligand expression in the pulmonary epithelium contributes to the development of COPD pathologies. PMID:19197141

  10. Physical activity and major non-communicable diseases among physicians in Central Saudi Arabia

    PubMed Central

    Mandil, Ahmed M.; Alfurayh, Nuha A.; Aljebreen, Manar A.; Aldukhi, Sarah A.

    2016-01-01

    Objectives: To evaluate levels of physical activity among physicians in Riyadh, Saudi Arabia and to study the possible factors affecting physical inactivity. In addition, the study aims to estimate the prevalence of major non-communicable diseases (NCDs) and a possible correlation between physical inactivity and major NCDs. Method: A cross-sectional approach was used for this study conducted on 370 randomly-selected outpatient physicians of both genders working at 4 leading healthcare institutions in Riyadh, Kindom of Saudi Arabia between December 2013 and January 2014. Using a modified World Health Organization (WHO) STEPwise questionnaire. Data was analyzed using the Statistical Package for Social Sciences version 21. Results: The findings of the present study demonstrated a prevalence of physical activity among Riyadh physicians (63%), which is higher than the general population (32.4%). The main reason for not engaging in physical activity was lack of time (58.1%) followed by work duties (22.5%). The prevalence of the most frequently reported NCDs (cardiovascular diseases, diabetes, chronic respiratory diseases, and cancers) was 21.9%. No significant association between physical inactivity and major NCDs among physicians in our sample was found. Conclusion: The participating physicians are physically active and suffer from a small percentage of the most reported NCDs. The main factor associated with physical inactivity was lack of time. No association was detected between physical inactivity and major NCDs. PMID:27761564

  11. [The biological and pharmacological activity of essential oils in the treatment and prevention of infectious diseases].

    PubMed

    Król, Sylwia Katarzyna; Skalicka-Woźniak, Krystyna; Kandefer-Szerszeń, Martyna; Stepulak, Andrzej

    2013-09-22

    Despite the large progress in medicine and pharmacy in the last few decades, traditional treatment of bacterial or viral diseases is frequently ineffective and is connected with some side effects. Currently, there is observed an increasing interest in natural plant-derived substances as a potential and promising group of medicines in prevention and treatment of several infectious diseases. Terpenes and their derivatives are a large class of natural organic components of essential oils and are widespread in the plant kingdom. Numerous experimental studies have shown that essential oils exhibit a large spectrum of biological and pharmacological activities in vitro. Herbal essential oils have been proved to possess antimicrobial, antiviral, antifungal and antiparasitic properties. They have also been reported to exhibit anti-inflammatory and immunostimulatory activities. Based on the wide spectrum of various biological activities, essential oils and terpenes commonly found in fruit, vegetables, herbs etc. have been suggested to constitute a novel group of preventive and therapeutic agents. Further experiments are necessary to confirm their pharmacological effectiveness, to determine potential toxic effects and the mechanism of their activity in in vivo models. This article describes the biological and pharmacological properties of herbal essential oils and some of their components, and summarizes the future prospects of potential application of essential oils in the prevention and treatment of infectious human diseases. In this review also possible mechanisms of their biological action are presented.

  12. Inflammatory synovial fluid microenvironment drives primary human chondrocytes to actively take part in inflammatory joint diseases.

    PubMed

    Röhner, Eric; Matziolis, Georg; Perka, Carsten; Füchtmeier, Bernd; Gaber, Timo; Burmester, Gerd-Rüdiger; Buttgereit, Frank; Hoff, Paula

    2012-06-01

    The role of human chondrocytes in the pathogenesis of cartilage degradation in rheumatic joint diseases has presently gained increasing interest. An active chondrocyte participation in local inflammation may play a role in the initiation and progression of inflammatory joint diseases and in a disruption of cartilage repair mechanisms resulting in cartilage degradation. In the present study, we hypothesized that inflammatory synovial fluid triggers human chondrocytes to actively take part in inflammatory processes in rheumatic joint diseases. Primary human chondrocytes were incubated in synovial fluids gained from patients with rheumatoid arthritis, psoriasis arthritis and reactive arthritis. The detection of vital cell numbers was determined by using Casy Cell Counter System. Apoptosis was measured by Annexin-V and 7AAD staining. Cytokine and chemokine secretion was determined by a multiplex suspension array. Detection of vital cells showed a highly significant decrease in chondrocyte numbers. Flow cytometry demonstrated a significant increase in apoptotic chondrocytes after the incubation. An active secretion of cytokines such as MCP-1 and MIF by chondrocytes was observed. The inflammatory synovial fluid microenvironment mediates apoptosis and cell death of chondrocytes. Moreover, in terms of cytokine secretion, it also induces an active participation of chondrocytes in ongoing inflammation.

  13. Common mental disorders and psychological distress in systemic lupus erythematosus are not associated with disease activity.

    PubMed

    Jarpa, E; Babul, M; Calderón, J; González, M; Martínez, M E; Bravo-Zehnder, M; Henríquez, C; Jacobelli, S; González, A; Massardo, L

    2011-01-01

    Psychiatric diagnosis in patients with systemic lupus erythematosus (SLE) is controversial: variations have been reported in frequency, diagnostic assays, associations with disease activity, autoantibodies, and contributing social factors. Eighty-three consecutive non-selected Chilean patients with SLE were evaluated for: (i) 26 common mental disorders according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), using the Mini-International Neuropsychiatric Interview (MINI-plus); (ii) psychological suffering measured by Hospital Anxiety and Depression Scale (HADS); (iii) ACR 1999 neuropsychiatric (NP)SLE criteria; (iv) SLE disease activity (SLEDAI-2K); (v) cumulative damage (SLICC/ACR); and (vi) anti-ribosomal P antibodies by enzyme-linked immunoassay and immunoblot. Psychiatric diagnoses occurred in 44.6% of patients; the most frequent (21.7%) was major depressive episode (MDE). No association with lupus activity was observed in patients with a DSM-IV diagnosis or MDE or psychological suffering. ACR 1999 NPSLE criteria were present in 42.2% of patients, the majority corresponding to mood (28.9%) or anxiety disorders (15.6%). Suicidal risk was present in 9.6% of patients. Anti-ribosomal P antibodies (13.3%) were not associated with DSM-IV diagnosis. Severe psychiatric disorders in SLE are common and not associated with disease activity.

  14. Correlation between enzyme activity and substrate storage in a cell culture model system for Gaucher disease.

    PubMed

    Schueler, U H; Kolter, T; Kaneski, C R; Zirzow, G C; Sandhoff, K; Brady, R O

    2004-01-01

    Gaucher disease, the most common sphingolipidosis, is caused by a decreased activity of glucosylceramide beta-glucosidase, resulting in the accumulation of glucosylceramide in macrophage-derived cells known as Gaucher cells. Much of the storage material is thought to originate from the turnover of cell membranes, such as phagocytosed red and white blood cells. In this study, an in vitro model of Gaucher disease was developed by treating the murine macrophage cell line J774 with a specific inhibitor of glucosylceramide beta-glucosidase, conduritol B-epoxide, and feeding red blood cell ghosts, in order to mimic the disease state. It was found in this model system that glucosylceramide beta-glucosidase activity could be reduced to about 11-15% of the normal control level before increased storage of glucosylceramide occurred. This in vitro system allows insight into the correlation between enzyme activity and lipid storage as predicted by the theory of residual enzyme activity that was proposed by Conzelmann and Sandhoff.

  15. Suppressor Mutations for Presenilin 1 Familial Alzheimer Disease Mutants Modulate γ-Secretase Activities.

    PubMed

    Futai, Eugene; Osawa, Satoko; Cai, Tetsuo; Fujisawa, Tomoya; Ishiura, Shoichi; Tomita, Taisuke

    2016-01-01

    γ-Secretase is a multisubunit membrane protein complex containing presenilin (PS1) as a catalytic subunit. Familial Alzheimer disease (FAD) mutations within PS1 were analyzed in yeast cells artificially expressing membrane-bound substrate, amyloid precursor protein, or Notch fused to Gal4 transcriptional activator. The FAD mutations, L166P and G384A (Leu-166 to Pro and Gly-384 to Ala substitution, respectively), were loss-of-function in yeast. We identified five amino acid substitutions that suppress the FAD mutations. The cleavage of amyloid precursor protein or Notch was recovered by the secondary mutations. We also found that secondary mutations alone activated the γ-secretase activity. FAD mutants with suppressor mutations, L432M or S438P within TMD9 together with a missense mutation in the second or sixth loops, regained γ-secretase activity when introduced into presenilin null mouse fibroblasts. Notably, the cells with suppressor mutants produced a decreased amount of Aβ42, which is responsible for Alzheimer disease. These results indicate that the yeast system is useful to screen for mutations and chemicals that modulate γ-secretase activity.

  16. No association of tobacco use and disease activity in multiple sclerosis

    PubMed Central

    Myhr, Kjell-Morten; Holmøy, Trygve; Benth, Jūratė Šaltytė; Løken-Amsrud, Kristin I.; Wergeland, Stig; Beiske, Antonie G.; Bjerve, Kristian S.; Hovdal, Harald; Lilleås, Finn; Midgard, Rune; Pedersen, Tom; Bakke, Søren J.; Torkildsen, Øivind

    2016-01-01

    Objective: To study whether tobacco use is associated with MRI and clinical disease activity in patients with multiple sclerosis (MS). Methods: Prospective cohort study of 87 patients with relapsing-remitting MS originally included in a randomized placebo-controlled trial of omega-3 fatty acids in MS (the OFAMS Study). Serum levels of cotinine (biomarker of tobacco use) were analyzed at baseline and every 6 months for 2 years. MRI activity was assessed at baseline and monthly for 9 months and after 12 and 24 months. Results: Fifty-three patients (61%) had serum cotinine levels ≥85 nmol/L on ≥60% of the measurements and were considered tobacco users and 34 (39%) had cotinine levels <85 nmol/L, consistent with non–tobacco use. There was no association between tobacco use and the occurrence of new gadolinium-enhancing T1 lesions, new or enlarging T2 lesions, or their aggregate (combined unique activity). Furthermore, there was no association between cotinine levels and MRI activity for the tobacco users, and tobacco users did not have more relapses or Expanded Disability Status Scale progression. Conclusion: Our results indicate that tobacco use does not directly influence MRI activity or relapse rate in MS. This may implicate that the reported association between smoking and MS disease progression could be mediated through other mechanisms. PMID:27458599

  17. Changes in activity and structure of jaw muscles in Parkinson's disease model rats.

    PubMed

    Nakamura, S; Kawai, N; Ohnuki, Y; Saeki, Y; Korfage, J A M; Langenbach, G E J; Kitayama, T; Watanabe, M; Sano, R; Tanne, K; Tanaka, E

    2013-03-01

    Parkinson's disease (PD), a major neurological disease, is characterised by a marked loss of dopaminergic neurons in the substantia nigra. Patients with PD frequently show chewing and swallowing dysfunctions, but little is known about the characteristics of their stomatognathic functions. The purpose of this study was to evaluate the influence of PD on jaw muscle fibre and functions. PD model rats were made by means of the injection of 6-hydroxydopamine (6-OHDA) into the striatum of 8-week-old Sprague-Dawley male rats. Five weeks after the injection, a radio-telemetric device was implanted to record muscle activity continuously from the superficial masseter and anterior belly of digastric muscles. Muscle activity was recorded for 3 days and was evaluated by the total duration of muscle activity per day (duty time). After recording the muscle activities, jaw muscles were isolated for immunohistochemical and PCR analyses. In PD model rats, the following findings of the digastrics muscles verify that compared to the control group: (i) the higher duty time exceeding 5% of the peak activity level, (ii) the higher expression of the mRNA of myosin heavy chain type I, and (iii) the tendency for fast to slow fibre-type transition. With respect to the masseter muscle, there were no significant differences in all analyses. In conclusion, PD leads to the changes in the jaw behaviours, resulting in a PD-specific chewing and swallowing dysfunctions.

  18. Cerebrovascular disease in HIV-infected individuals in the era of highly active antiretroviral therapy.

    PubMed

    Cruse, Belinda; Cysique, Lucette A; Markus, Romesh; Brew, Bruce J

    2012-08-01

    The widespread use of highly active antiretroviral therapy (HAART) in HIV-infected individuals mostly in developed countries has dramatically improved their prognosis. In such advantaged regions of the world, therefore, many patients are now transitioning from middle into older age, with altered patterns of disease. While previously a rare complication of HIV infection, cerebrovascular disease (particularly that associated with atherosclerosis) is becoming relatively more important in this treated group of individuals. This review summarises the evidence regarding the shifting epidemiology of cerebrovascular diseases affecting HIV-infected individuals. While outlining the association between HIV infection and AIDS and cerebrovascular disease, as well as opportunistic diseases and HIV-associated vasculopathies, the current evidence supporting an increase in atherosclerotic disease in treated HIV-infected individuals is emphasised and a management approach to ischaemic stroke in HIV-infected individuals is presented. Evidence supporting the important role of HAART and HIV infection itself in the pathogenesis of atherosclerotic disease is discussed, together with preventative approaches to this increasingly important disease process as the population ages. Finally, a discussion regarding the significant association between cerebrovascular disease and HIV-associated neurocognitive disorder is presented, together with possible mechanisms behind this relationship.

  19. Coagulation Activation in Children with Sickle Cell Disease Is Associated with Cerebral Small Vessel Vasculopathy

    PubMed Central

    Colombatti, Raffaella; De Bon, Emiliano; Bertomoro, Antonella; Casonato, Alessandra; Pontara, Elena; Omenetto, Elisabetta; Saggiorato, Graziella; Steffan, Agostino; Damian, Tamara; Cella, Giuseppe; Teso, Simone; Manara, Renzo; Rampazzo, Patrizia; Meneghetti, Giorgio; Basso, Giuseppe; Sartori, Maria Teresa; Sainati, Laura

    2013-01-01

    Background Thrombotic complications in Sickle Cell Disease (SCD) arise since infancy, but the role of the coagulation system in children has been poorly explored. To determine its role in the development of clinical complications in childhood we measured coagulation and endothelial parameters in children with SCD at steady state. Methods Markers of thrombin generation, fibrin dissolution and endothelial activation were evaluated in 38 children with SS-Sβ°, 6 with SC disease and 50 age and blood group matched controls. Coagulation variables were correlated with markers of hemolysis and inflammation, with the presence of cerebral and lung vasculopathy and with the frequency of clinical complications. Results SS-Sβ° patients presented higher levels of factor VIII, von Willebrand factor antigen (VWF:Ag) and collagen binding activity, tissue plasminogen activator antigen (t-PA:Ag), D-dimer, p-selectin, prothrombin fragment1+2 (F1+2) and lower ADAMTS-13:activity/VWF:Ag (p<0.05) compared to controls and SC patients. In SS-Sβ° patients coagulation variables correlated positively with markers of inflammation, hemolysis, and negatively with HbF (p<0.05). Patients with cerebral silent infarcts showed significant decrease in t-PA:Ag and ADAMTS-13 Antigen and a tendency toward higher D-dimer, F1+2, TAT compared to patients without them. D-dimer was associated with a six fold increased risk of cerebral silent infarcts. No correlation was found between coagulation activation and large vessel vasculopathy or other clinical events except for decreased t-PA:Ag in patients with tricuspid Rigurgitant Velocity >2.5m/sec. Conclusions SS-Sβ° disease is associated with extensive activation of the coagulation system at steady state since young age. ADAMTS-13 and t-PA:Ag are involved in the development of cerebral silent infarcts. PMID:24205317

  20. Alkaloids Pharmacological Activities - Prospects for the Development of Phytopharmaceuticals for Neurodegenerative Diseases.

    PubMed

    Chaves, Soane K M; Feitosa, Chistiane M; da S Araújo, Lidiane

    The study of natural substances has increased in recent years in the search for compounds with pharmacological properties that can be used for the development of new drugs. The alkaloids, substances extracted natural sources, show promising pharmacological activities, including pharmacological activities for the treatment of neurodegenerative diseases such as Alzheimer's disease, whose treatment is based on the use of various drugs. Thus, the article aims to a technological prospecting of alkaloids that presented important properties in the treatment of neurodegenerative diseases, namely, antioxidant, anxiolytic, anti-inflammatory and antidepressant properties. A literature review was conducted in the databases PubMed, Science Direct, Scopus, Scielo and Google Academics using the following key words: alkaloids, pharmacology, neurodegenerative diseases, cholinesterase inhibitors, antidepressants, anti-inflammatories, antioxidant and anxiolytic. Articles, dissertations and theses published between 2003 and 2015 were selected. Several studies showed through in vitro of in vitro and/or in vivo methods that many alkaloids extracted from plants showed anticholinesterase, antioxidant, anxiolytic, anti-inflammatory and antidepressant properties in the treatment of symptoms and progression of certain diseases such as Alzheimer's disease.

  1. Investigation of the association between metabolic syndrome and disease activity in rheumatoid arthritis.

    PubMed

    Sahebari, Maryam; Goshayeshi, Ladan; Mirfeizi, Zahra; Rezaieyazdi, Zahra; Hatef, Mohammad R; Ghayour-Mobarhan, Majid; Akhlaghi, Saeed; Sahebkar, Amirhossein; Ferns, Gordon A

    2011-06-09

    Rheumatoid arthritis (RA) is the most common form of autoimmune arthritis. Increased prevalence of metabolic syndrome (MetS) in RA may occur secondary to specific drug treatment and reduced physical activity associated with this condition. However, some recent studies suggest contradictory theories about the association of RA with MetS. This study was designed to evaluate the frequency of MetS in RA patients and the relationship between MetS with RA disease activity and body mass index (BMI). The study was conducted on 120 RA patients and 431 age- and sex-matched apparently healthy controls. A considerable proportion of patients were being treated with prednisolone and/or methotrexate and/or hydroxychloroquine. Disease activity was measured by the 28 joint count of disease activity score-Cerythrocyte sedimentation rate (DAS28ESR). MetS was evaluated according to International Diabetic Federation (IDF) and Adult Treatment Panel III (ATP III) criteria. The prevalence of MetS was significantly higher in the control group (p = 0.005). We did not find any difference in the prevalence of MetS between the patients with DAS < 3.2 and DAS ≥ 3.2. There was no association between the DAS28 score and the presence of MetS components by either definition. Multiple logistic regression analysis showed that the odds of a DAS > 3.2 in patients with BMI between 25 and 30 kg/m2 (OR = 0.1, p = 0.01) and BMI > 30 kg/m2 (OR = 0.3, p = 0.1), in comparison to BMI < 25 kg/m2, was 1/5 and 1/3, respectively. RA was not found to increase the risk of MetS. In addition, disease activity in RA patients was not influenced by the presence of MetS.

  2. Relationship between electromyographic activity and clinically assessed rigidity studied at the wrist joint in Parkinson's disease.

    PubMed

    Meara, R J; Cody, F W

    1992-08-01

    The electromyographic (EMG) patterns recorded from wrist muscles during manually applied, repetitive flexion and extension movements of the wrist joint, used for simultaneous clinical assessment of rigidity, were studied in patients with Parkinson's disease and healthy subjects. Recordings were made whilst patients/subjects attempted voluntarily to relax the muscle of the arm whose wrist joint was manipulated. Individual patients were investigated before and at varying times after their routine daily medication as their clinical rigidity underwent associated modulations. It was often possible to induce additional alterations in clinical rigidity by instructing patients to perform an activation or Jendrassik-like manoeuvre (clenching the contralateral fist). In rigid patients, the approximately sinusoidal wrist displacements (60 deg, 1-1.5 Hz) typically elicited pronounced, cyclic modulations of EMG activities in wrist flexors and extensors; increases in EMG activity were phase-locked to the respective periods of muscle stretch. Stretch-related EMG activity reduced or disappeared as rigidity was abolished by drug therapy. The EMG patterns of patients showing cogwheel rigidity featured discrete, phasic bursts superimposed upon more generalized stretch-related increases in activity. In healthy subjects, showing no clinical rigidity, the pronounced cyclic modulations of EMG activity characteristic of rigid patients were absent during similar manually applied wrist displacements. Quantitative EMG measurements for individual patients, made 'on' and 'off' medication and as their rigidity fluctuated, indicated that mild (grade 1) and moderate (grade 2) rigidity was consistently associated with increased stretch-related activity compared with non-rigid conditions. Pair-wise statistical analysis indicated such increases in EMG to be significant. Similarly, the ratios of EMG activities in the stretched versus released muscles were significantly greater for grades 1 and 2

  3. Mitochondrial superoxide flashes: metabolic biomarkers of skeletal muscle activity and disease

    PubMed Central

    Wei, Lan; Salahura, Gheorghe; Boncompagni, Simona; Kasischke, Karl A.; Protasi, Feliciano; Sheu, Shey-Shing; Dirksen, Robert T.

    2011-01-01

    Mitochondrial superoxide flashes (mSOFs) are stochastic events of quantal mitochondrial superoxide generation. Here, we used flexor digitorum brevis muscle fibers from transgenic mice with muscle-specific expression of a novel mitochondrial-targeted superoxide biosensor (mt-cpYFP) to characterize mSOF activity in skeletal muscle at rest, following intense activity, and under pathological conditions. Results demonstrate that mSOF activity in muscle depended on electron transport chain and adenine nucleotide translocase functionality, but it was independent of cyclophilin-D-mediated mitochondrial permeability transition pore activity. The diverse spatial dimensions of individual mSOF events were found to reflect a complex underlying morphology of the mitochondrial network, as examined by electron microscopy. Muscle activity regulated mSOF activity in a biphasic manner. Specifically, mSOF frequency was significantly increased following brief tetanic stimulation (18.1±1.6 to 22.3±2.0 flashes/1000 μm2·100 s before and after 5 tetani) and markedly decreased (to 7.7±1.6 flashes/1000 μm2·100 s) following prolonged tetanic stimulation (40 tetani). A significant temperature-dependent increase in mSOF frequency (11.9±0.8 and 19.8±2.6 flashes/1000 μm2·100 s at 23°C and 37°C) was observed in fibers from RYR1Y522S/WT mice, a mouse model of malignant hyperthermia and heat-induced hypermetabolism. Together, these results demonstrate that mSOF activity is a highly sensitive biomarker of mitochondrial respiration and the cellular metabolic state of muscle during physiological activity and pathological oxidative stress.—Wei, L., Salahura, G., Boncompagni, S., Kasischke, K. A., Protasi, F., Sheu, S.-S., Dirksen, R. T. Mitochondrial superoxide flashes: metabolic biomarkers of skeletal muscle activity and disease. PMID:21646399

  4. Beyond endoscopic assessment in inflammatory bowel disease: real-time histology of disease activity by non-linear multimodal imaging

    NASA Astrophysics Data System (ADS)

    Chernavskaia, Olga; Heuke, Sandro; Vieth, Michael; Friedrich, Oliver; Schürmann, Sebastian; Atreya, Raja; Stallmach, Andreas; Neurath, Markus F.; Waldner, Maximilian; Petersen, Iver; Schmitt, Michael; Bocklitz, Thomas; Popp, Jürgen

    2016-07-01

    Assessing disease activity is a prerequisite for an adequate treatment of inflammatory bowel diseases (IBD) such as Crohn’s disease and ulcerative colitis. In addition to endoscopic mucosal healing, histologic remission poses a promising end-point of IBD therapy. However, evaluating histological remission harbors the risk for complications due to the acquisition of biopsies and results in a delay of diagnosis because of tissue processing procedures. In this regard, non-linear multimodal imaging techniques might serve as an unparalleled technique that allows the real-time evaluation of microscopic IBD activity in the endoscopy unit. In this study, tissue sections were investigated using the non-linear multimodal microscopy combination of coherent anti-Stokes Raman scattering (CARS), two-photon excited auto fluorescence (TPEF) and second-harmonic generation (SHG). After the measurement a gold-standard assessment of histological indexes was carried out based on a conventional H&E stain. Subsequently, various geometry and intensity related features were extracted from the multimodal images. An optimized feature set was utilized to predict histological index levels based on a linear classifier. Based on the automated prediction, the diagnosis time interval is decreased. Therefore, non-linear multimodal imaging may provide a real-time diagnosis of IBD activity suited to assist clinical decision making within the endoscopy unit.

  5. Beyond endoscopic assessment in inflammatory bowel disease: real-time histology of disease activity by non-linear multimodal imaging

    PubMed Central

    Chernavskaia, Olga; Heuke, Sandro; Vieth, Michael; Friedrich, Oliver; Schürmann, Sebastian; Atreya, Raja; Stallmach, Andreas; Neurath, Markus F.; Waldner, Maximilian; Petersen, Iver; Schmitt, Michael; Bocklitz, Thomas; Popp, Jürgen

    2016-01-01

    Assessing disease activity is a prerequisite for an adequate treatment of inflammatory bowel diseases (IBD) such as Crohn’s disease and ulcerative colitis. In addition to endoscopic mucosal healing, histologic remission poses a promising end-point of IBD therapy. However, evaluating histological remission harbors the risk for complications due to the acquisition of biopsies and results in a delay of diagnosis because of tissue processing procedures. In this regard, non-linear multimodal imaging techniques might serve as an unparalleled technique that allows the real-time evaluation of microscopic IBD activity in the endoscopy unit. In this study, tissue sections were investigated using the non-linear multimodal microscopy combination of coherent anti-Stokes Raman scattering (CARS), two-photon excited auto fluorescence (TPEF) and second-harmonic generation (SHG). After the measurement a gold-standard assessment of histological indexes was carried out based on a conventional H&E stain. Subsequently, various geometry and intensity related features were extracted from the multimodal images. An optimized feature set was utilized to predict histological index levels based on a linear classifier. Based on the automated prediction, the diagnosis time interval is decreased. Therefore, non-linear multimodal imaging may provide a real-time diagnosis of IBD activity suited to assist clinical decision making within the endoscopy unit. PMID:27406831

  6. Have guidelines addressing physical activity been established in nonalcoholic fatty liver disease?

    PubMed Central

    Finelli, Carmine; Tarantino, Giovanni

    2012-01-01

    The purpose of this review was to highlight, in relation to the currently accepted pathophysiology of non-alcoholic fatty liver disease (NAFLD), the known exercise habits of patients with NAFLD and to detail the benefits of lifestyle modification with exercise (and/or physical activity) on parameters of metabolic syndrome. More rigorous, controlled studies of longer duration and defined histopathological end-points comparing exercise alone and other treatment are needed before better, evidence-based physical activity modification guidelines can be established, since several questions remain unanswered. PMID:23239917

  7. Increased oxidative stress in pemphigus vulgaris is related to disease activity and HLA-association.

    PubMed

    Shah, Amit Aakash; Dey-Rao, Rama; Seiffert-Sinha, Kristina; Sinha, Animesh A

    2016-06-01

    Pemphigus vulgaris (PV) is a rare blistering skin disorder characterized by the disadhesion of keratinocytes due to autoantibody attack against epidermal targets including desmoglein (Dsg) 3, Dsg 1 and possibly other adhesion and non-adhesion molecules. The mechanisms leading to immune-mediated pathology in PV are multifactorial and not fully understood. Recently, oxidative stress (antioxidant/oxidant disequilibrium) has been proposed as a contributory mechanism of autoimmune skin diseases, including PV. In this study, we directly assessed oxidative stress via measurement of total antioxidant capacity (TAC) using ELISA in 47 PV patients, 25 healthy controls and 18 bullous pemphigoid (BP) patients. We also performed microarray gene expression analysis on a separate set of 21 PV patients and 10 healthy controls to evaluate transcriptional dysregulation in oxidative stress-related pathways. Our data indicate that there is a significant reduction in TAC levels in PV patients compared with healthy controls, as well as BP patients. Furthermore, PV patients with active disease have significantly lower TAC levels than PV patients in remission. We also find that HLA allele status has a significant influence on oxidative stress. These findings are corroborated by microarray analysis showing differentially expressed genes involved in oxidative stress between the aforementioned groups. Collectively, our findings provide support for a role of oxidative stress in PV. Whether increased oxidative stress leads to disease manifestation and/or activity, or if disease activity leads to increased oxidative stress remains unknown. Future longitudinal studies may help to further elucidate the relationship between PV and oxidative stress.

  8. Aerobic capacity correlates to self-assessed physical function but not to overall disease activity or organ damage in women with systemic lupus erythematosus with low-to-moderate disease activity and organ damage.

    PubMed

    Boström, C; Dupré, B; Tengvar, P; Jansson, E; Opava, C H; Lundberg, I E

    2008-02-01

    The present aim is to investigate the relationships between aerobic capacity and disease activity, organ damage, health-related quality of life (HRQL) and physical activity in 34 women with systemic lupus erythematosus (SLE) with low-to-moderate disease activity and organ damage. Mean age was 51 (SD 10) years, disease duration 17 (SD 11) years. Aerobic capacity (maximal oxygen uptake/VO2 max) was measured with a bicycle ergometer exercise test. Overall disease activity was assessed with Systemic Lupus Activity Measure (SLAM) and the modified Systemic Lupus Erythematosus-Disease Activity Index (modified SLE-DAI), overall organ damage with the Systemic Lupus International Collaboration Clinics/American College of Rheumatology-Damage Index, [SLICC/(ACR)-DI], HRQL with the 36-item Short-form health-survey (SF-36) and physical activity with a self-assessed question. The women who were low-to-moderately physically active had 89-92% (P < or = 0.001) of VO2 max predicted for sedentary women. Maximal oxygen uptake (L/min, mL/min/kg) correlated to SF-36 physical function (rs = 0.49, rs = 0.72) (P < or = 0.01), but not (rs < or = 0.25) to other HRQL scales, overall disease activity or organ damage or physical activity. The correlation between aerobic capacity and physical function and the absence of correlation between aerobic capacity and physical activity, suggest a possible disease-related factor behind the low aerobic capacity. However, with no correlation between aerobic capacity and overall disease activity and organ damage, low physical activity may contribute to the low aerobic capacity in our sample.

  9. Patterns of Longitudinal Neural Activity Linked to Different Cognitive Profiles in Parkinson's Disease

    PubMed Central

    Nagano-Saito, Atsuko; Al-Azzawi, Mohamed S.; Hanganu, Alexandru; Degroot, Clotilde; Mejia-Constain, Béatriz; Bedetti, Christophe; Lafontaine, Anne-Louise; Soland, Valérie; Chouinard, Sylvain; Monchi, Oury

    2016-01-01

    Mild cognitive impairment in Parkinson's disease (PD) has been linked with functional brain changes. Previously, using functional magnetic resonance imaging (fMRI), we reported reduced cortico-striatal activity in patients with PD who also had mild cognitive impairment (MCI) vs. those who did not (non-MCI). We followed up these patients to investigate the longitudinal effect on the neural activity. Twenty-four non-demented patients with Parkinson's disease (non-MCI: 12, MCI: 12) were included in the study. Each participant underwent two fMRIs while performing the Wisconsin Card Sorting Task 20 months apart. The non-MCI patients recruited the usual cognitive corticostriatal loop at the first and second sessions (Time 1 and Time 2, respectively). However, decreased activity was observed in the cerebellum and occipital area and increased activity was observed in the medial prefrontal cortex and parietal lobe during planning set-shift at Time 2. Increased activity in the precuneus was also demonstrated while executing set-shifts at Time 2. The MCI patients revealed more activity in the frontal, parietal and occipital lobes during planning set-shifts, and in the parietal and occipital lobes, precuneus, and cerebellum, during executing set-shift at Time 2. Analysis regrouping of both groups of PD patients revealed that hippocampal and thalamic activity at Time 1 was associated with less cognitive decline over time. Our results reveal that functional alteration along the time-points differed between the non-MCI and MCI patients. They also underline the importance of preserving thalamic and hippocampal function with respect to cognitive decline over time. PMID:27932974

  10. Judging disease activity in rheumatoid arthritis by serum free kappa and lambda light chain levels.

    PubMed

    Ye, Yun; Li, Su-Liang; Xie, Ming; Jiang, Ping; Liu, Kai-Ge; Li, Ya-Jun

    2013-10-01

    The study aimed to evaluate the levels of serum free kappa (κ) and lambda (λ) light chains in patients with rheumatoid arthritis (RA) as well as exploring the association between serum free κ and λ light chains and activity of RA. For this purpose, healthy individuals and patients with active RA and RA in remission were enrolled, and their serum levels of free κ and λ light chains were measured using rate nephelometry. The diagnostic accuracy of serum free κ and λ light chains was evaluated by receiver operating characteristic curves and 95% confidence intervals for areas under the curve (AUC). The results obtained indicated that the levels of serum free κ and λ light chains in patients with active RA were significantly higher than those of patients in remission and of healthy controls (p < 0.05). Further, the AUC values in patients with active RA were 0.871 for free κ light chain and 0.781 for free λ light chain. When the optimal cut-off point for serum κ light chain was 8.02 g/L, the maximum sensitivity and specificity were 82.5% and 82.5%, respectively, and when the optimal cut-off point for serum λ light chain was 3.57 g/L, the maximum sensitivity and specificity were 80% and 82.5%, respectively. It was thus found that serum levels of free κ and λ light chains were positively correlated with disease activity in RA, the Disease Activity Score 28 (DAS28), and values for C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), platelet count (PLT), rheumatoid factor (RF), and anticitrullinated protein antibody (ACPA) (p < 0.05). In conclusion, high serum levels of free κ and λ light chains in patients with active RA are closely correlated with disease activity parameters including DAS28, CRP, ESR, PLT, RF, and ACPA. Thus, the above-mentioned levels of serum free κ and λ light chains may be used as important indicators of activity of RA.

  11. Novel specific microRNA biomarkers in idiopathic inflammatory bowel disease unrelated to disease activity.

    PubMed

    Lin, Jingmei; Welker, Noah C; Zhao, Zijin; Li, Yong; Zhang, Jianjun; Reuss, Sarah A; Zhang, Xinjun; Lee, Hwajeong; Liu, Yunlong; Bronner, Mary P

    2014-04-01

    The diagnosis of idiopathic inflammatory bowel disease can be challenging. MicroRNAs (miRNAs) are small, non-coding RNAs that regulate protein synthesis through post-transcriptional suppression. This study is to identify new miRNA markers in inflammatory bowel disease, and to examine whether miRNA biomarkers might assist in the diagnosis of inflammatory bowel disease. Illumina small RNA sequencing was performed on non-dysplastic fresh-frozen colonic mucosa samples of the distalmost colectomy tissue from 19 patients with inflammatory bowel disease (10 ulcerative colitis and 9 Crohn disease) and 18 patients with diverticular disease serving as controls. To determine differentially expressed miRNAs, the USeq software package identified 44 miRNAs with altered expression (fold change ≥ 2 and false discovery rate ≤ 0.10) compared with the controls. Among them, a panel of nine miRNAs was aberrantly expressed in both ulcerative colitis and Crohn disease. Validation assays performed using quantitative reverse transcription PCR (qRT-PCR) on additional frozen tissue from ulcerative colitis, Crohn disease, and control groups confirmed specific differential expression in inflammatory bowel disease for miR-31, miR-206, miR-424, and miR-146a (P<0.05). The expression of these four miRNAs was further evaluated on formalin-fixed, paraffin-embedded tissue of the distalmost colectomy mucosa from cohorts of diverticular disease controls (n=29), ulcerative colitis (n=36), Crohn disease (n=26), and the other diseases mimicking inflammatory bowel disease including infectious colitis (n=12) and chronic ischemic colitis (n=19), again confirming increased expression specific to inflammatory bowel disease (P<0.05). In summary, we demonstrate that miR-31, miR-206, miR-424, and miR-146a are novel specific biomarkers of inflammatory bowel disease. Furthermore, miR-31 is universally expressed in both ulcerative colitis and Crohn disease not only in fresh-frozen but also in formalin

  12. Pomegranate polyphenols and extract inhibit nuclear factor of activated T-cell activity and microglial activation in vitro and in a transgenic mouse model of Alzheimer disease.

    PubMed

    Rojanathammanee, Lalida; Puig, Kendra L; Combs, Colin K

    2013-05-01

    Alzheimer disease (AD) brain is characterized by extracellular plaques of amyloid β (Aβ) peptide with reactive microglia. This study aimed to determine whether a dietary intervention could attenuate microgliosis. Memory was assessed in 12-mo-old male amyloid precursor protein/presenilin 1 (APP/PS1) transgenic mice via Barnes maze testing followed by division into either a control-fed group provided free access to normal chow and water or a treatment group provided free access to normal chow and drinking water supplemented with pomegranate extract (6.25 mL/L) for 3 mo followed by repeat Barnes maze testing for both groups. Three months of pomegranate feeding decreased the path length to escape of mice compared with their initial 12-mo values (P < 0.05) and their control-fed counterparts (P < 0.05). Brains of the 3-mo study pomegranate-fed mice had lower tumor necrosis factor α (TNF-α) concentrations (P < 0.05) and lower nuclear factor of activated T-cell (NFAT) transcriptional activity (P < 0.05) compared with controls. Brains of the 3-mo pomegranate or control mice were also compared with an additional control group of 12-mo-old mice for histologic analysis. Immunocytochemistry showed that pomegranate- but not control-fed mice had attenuated microgliosis (P < 0.05) and Aβ plaque deposition (P < 0.05) compared with 12-mo-old mice. An additional behavioral study again used 12-mo-old male APP/PS1 mice tested by T-maze followed by division into a control group provided with free access to normal chow and sugar supplemented drinking water or a treatment group provided with normal chow and pomegranate extract-supplemented drinking water (6.25 mL/L) for 1 mo followed by repeat T-maze testing in both groups. One month of pomegranate feeding increased spontaneous alternations versus control-fed mice (P < 0.05). Cell culture experiments verified that 2 polyphenol components of pomegranate extract, punicalagin and ellagic acid, attenuated NFAT activity in a reporter cell

  13. Public Awareness and Knowledge of Neglected Tropical Diseases (NTDs) Control Activities in Abuja, Nigeria

    PubMed Central

    Olamiju, Olatunwa J.; Olamiju, Francisca O.; Adeniran, Adebiyi A.; Mba, Ifeanyi C.; Ukwunna, Chidera C.; Okoronkwo, Chukwu; Ekpo, Uwem F.

    2014-01-01

    The need to engage the public in Neglected Tropical Diseases (NTDs) control activities has become imperative in the context of morbidity reduction through preventive chemotherapy and community participation. Therefore, a survey was conducted among the general public to assess their knowledge and awareness of NTDs control activities in Nigeria. A simple questionnaire was administered to the general public attending a job fair in Abuja, Nigeria. Of the 461 respondents, a significant proportion 337 (73.1%) have heard of NTD before, but only 291 (63.1%) have good knowledge about NTDs. However, among the specific NTDs, only the control of onchocerciasis (50.8%) was of average public awareness in Nigeria, while all the other NTDs control activities were significantly less known to the general public. 397 (87.1%) stated that government support for NTD control activities is poor and were willing to assist to advocate for NTDs control. This survey demonstrates that despite government's numerous activities towards the control of NTDs in Nigeria, there is little sensitization of the general public. There is a need for policy changes that would raise the participation and involvement of the general public in NTDs control activities for sustainability. PMID:25254362

  14. The clinical utility of basophil activation testing in diagnosis and monitoring of allergic disease.

    PubMed

    Hoffmann, H J; Santos, A F; Mayorga, C; Nopp, A; Eberlein, B; Ferrer, M; Rouzaire, P; Ebo, D G; Sabato, V; Sanz, M L; Pecaric-Petkovic, T; Patil, S U; Hausmann, O V; Shreffler, W G; Korosec, P; Knol, E F

    2015-11-01

    The basophil activation test (BAT) has become a pervasive test for allergic response through the development of flow cytometry, discovery of activation markers such as CD63 and unique markers identifying basophil granulocytes. Basophil activation test measures basophil response to allergen cross-linking IgE on between 150 and 2000 basophil granulocytes in <0.1 ml fresh blood. Dichotomous activation is assessed as the fraction of reacting basophils. In addition to clinical history, skin prick test, and specific IgE determination, BAT can be a part of the diagnostic evaluation of patients with food-, insect venom-, and drug allergy and chronic urticaria. It may be helpful in determining the clinically relevant allergen. Basophil sensitivity may be used to monitor patients on allergen immunotherapy, anti-IgE treatment or in the natural resolution of allergy. Basophil activation test may use fewer resources and be more reproducible than challenge testing. As it is less stressful for the patient and avoids severe allergic reactions, BAT ought to precede challenge testing. An important next step is to standardize BAT and make it available in diagnostic laboratories. The nature of basophil activation as an ex vivo challenge makes it a multifaceted and promising tool for the allergist. In this EAACI task force position paper, we provide an overview of the practical and technical details as well as the clinical utility of BAT in diagnosis and management of allergic diseases.

  15. Accelerometry-Based Activity Recognition and Assessment in Rheumatic and Musculoskeletal Diseases

    PubMed Central

    Billiet, Lieven; Swinnen, Thijs Willem; Westhovens, Rene; de Vlam, Kurt; Van Huffel, Sabine

    2016-01-01

    One of the important aspects to be considered in rheumatic and musculoskeletal diseases is the patient’s activity capacity (or performance), defined as the ability to perform a task. Currently, it is assessed by physicians or health professionals mainly by means of a patient-reported questionnaire, sometimes combined with the therapist’s judgment on performance-based tasks. This work introduces an approach to assess the activity capacity at home in a more objective, yet interpretable way. It offers a pilot study on 28 patients suffering from axial spondyloarthritis (axSpA) to demonstrate its efficacy. Firstly, a protocol is introduced to recognize a limited set of six transition activities in the home environment using a single accelerometer. To this end, a hierarchical classifier with the rejection of non-informative activity segments has been developed drawing on both direct pattern recognition and statistical signal features. Secondly, the recognized activities should be assessed, similarly to the scoring performed by patients themselves. This is achieved through the interval coded scoring (ICS) system, a novel method to extract an interpretable scoring system from data. The activity recognition reaches an average accuracy of 93.5%; assessment is currently 64.3% accurate. These results indicate the potential of the approach; a next step should be its validation in a larger patient study. PMID:27999255

  16. Oscillatory pallidal local field potential activity inversely correlates with limb dyskinesias in Parkinson's disease.

    PubMed

    Silberstein, Paul; Oliviero, Antonio; Di Lazzaro, Vincenzo; Insola, Angelo; Mazzone, Paolo; Brown, Peter

    2005-08-01

    Levodopa induced dyskinesias (LIDs) are poorly understood and yet are a major cause of disability in Parkinson's disease (PD). The activity of neurons in the basal ganglia of patients with PD tends to be strongly synchronized at frequencies under 30 Hz, leading to oscillatory local field potentials (LFPs). As dopaminergic therapy acutely suppresses this synchronization, we investigated whether this suppression may contribute to LIDs. Accordingly, we sought an inverse correlation between oscillatory synchronization and dyskinesia activity across time. To this end, we recorded pallidal LFPs in two Parkinsonian subjects exhibiting LIDs following surgery for deep brain stimulation. We correlated LFP power with simultaneously recorded EMG from the dyskinetic contralateral upper limb. We found highly significant inverse correlations between the oscillatory LFP activity under 30 Hz and dyskinetic EMG (maximum r = -0.65, P < 0.001 and r = -0.33, P < 0.001 for activities over 13-30 Hz in each subject). The inverse relationship between oscillatory pallidal LFP activity and dyskinetic EMG was maintained over time periods of a few seconds and was focal. This observation links the suppression of oscillatory synchronization in the pallidum with dyskinetic muscle activity in PD.

  17. Declining physical capacity but maintained aerobic activity in early Alzheimer's disease.

    PubMed

    Cedervall, Ylva; Kilander, Lena; Aberg, Anna Cristina

    2012-05-01

    The longitudinal influences on physical capacity and habitual aerobic activity level in the early stages of Alzheimer's disease (AD) are unclear. Therefore, changes in physical capacity and aerobic activity level were evaluated. Twenty-five individuals with AD were assessed annually for 2 years, by 10-m walk test, 6-minute walk test, and timed up-and-go (TUG) single/dual tasks. Habitual aerobic activity was assessed by diary registrations. The AD group showed a lower physical capacity than controls at baseline but comparable levels of aerobic activity. During the follow-up period, physical capacity declined in the AD group, but the aerobic activity levels changed only marginally. Our results show that in the early stages of AD, people are capable of maintaining health-promoting aerobic activity levels, despite a decline in their physical capacity. Additionally, it appears that cognitive dysfunction contributes to an impaired physical capacity. The TUG tasks might, therefore, be useful for detecting early signs of cognitive impairment.

  18. UPDRS activity of daily living score as a marker of Parkinson's disease progression.

    PubMed

    Harrison, Madaline B; Wylie, Scott A; Frysinger, Robert C; Patrie, James T; Huss, Diane S; Currie, Lillian J; Wooten, G Frederick

    2009-01-30

    The activities of daily living (ADL) subscore of the Unified Parkinson's Disease Rating Scale (UPDRS) captures the impact of Parkinson's disease (PD) on daily function and may be less affected than other subsections by variability associated with drug cycle and motor fluctuations. We examined UPDRS mentation, ADL and motor subscores in 888 patients with idiopathic PD. Multiple linear regression analyses determined the association between disease duration and UPDRS subscores as a function of medication status at examination and in a subset of patients with multiple examinations. Independent of medication status and across cross-sectional and longitudinal analyses, ADL subscores showed a stronger and more stable association with disease duration than other UPDRS subscores after adjusting for age of disease onset. The association between disease duration and the motor subscore depended on medication status. The strong association between ADL subscore and disease duration in PD suggests that this measure may serve as a better marker of disease progression than signs and symptoms assessed in other UPDRS sections.

  19. The relationship between disease activity and depression and sleep quality in Behçet's disease patients.

    PubMed

    Koca, Irfan; Savas, Esen; Ozturk, Zeynel Abidin; Tutoglu, Ahmet; Boyaci, Ahmet; Alkan, Samet; Kisacik, Bünyamin; Onat, Ahmet Mesut

    2015-07-01

    Like many chronic illnesses, Behçet's disease (BD) has been reported to negatively affect the quality of life and mental health of the individuals diagnosed with this disease. This study aims to investigate the relationship between disease activity and depression and sleep quality in BD. Forty patients with BD and 30 healthy subjects (controls), aged 18-65, were included in this study, and all of the subjects enrolled in this study were assessed in terms of depression and sleep quality using the Beck depression index (BDI) and Pittsburg sleep quality index (PSQI). Additionally, the subjects with BD were also assessed using the Behçet's disease current activity form (BDCAF). It was determined that the depression and sleep quality scores were significantly higher in the BD group compared to those in the control group (p = 0.012 and p = 0.020, respectively), and in the BD group, significant positive correlations were determined between the BDCAF and depression and sleep quality scores (r = 0.559, p < 0.001 and r = 0.462, p = 0.003, respectively). We believe that the assessment of BD patients for depressive symptoms and sleep quality, and providing medical support to those who need it, will contribute to the treatment and follow-up processes of BD.

  20. Peroxisome Proliferator-Activated Receptor Modulation during Metabolic Diseases and Cancers: Master and Minions

    PubMed Central

    Nigro, Angela; La Rosa, Valentina Lucia; Rossetti, Paola; Rapisarda, Agnese Maria Chiara; Condorelli, Rosita Angela; Corrado, Francesco; Buscema, Massimo

    2016-01-01

    The prevalence of obesity and metabolic diseases (such as type 2 diabetes mellitus, dyslipidaemia, and cardiovascular diseases) has increased in the last decade, in both industrialized and developing countries. This also coincided with our observation of a similar increase in the prevalence of cancers. The aetiology of these diseases is very complex and involves genetic, nutritional, and environmental factors. Much evidence indicates the central role undertaken by peroxisome proliferator-activated receptors (PPARs) in the development of these disorders. Due to the fact that their ligands could become crucial in future target-therapies, PPARs have therefore become the focal point of much research. Based on this evidence, this narrative review was written with the purpose of outlining the effects of PPARs, their actions, and their prospective uses in metabolic diseases and cancers. PMID:28115924

  1. Advances in the assessment of disease activity in inflammatory bowel disease

    SciTech Connect

    Camilleri, M.; Proano, M. )

    1989-07-01

    Knowledge of the severity and extent of the inflammation in inflammatory bowel diseases provides a means of determining rational therapeutic strategies in affected patients. During the past 3 decades, several clinical, laboratory, and combined indices have been proposed for the assessment of inflammatory bowel disease; refinements in radiologic methods and the availability of endoscopy and biopsy have facilitated the accurate assessment of the extent and severity of the disease. In relapsing conditions such as inflammatory bowel disease, however, the use of such procedures is limited by the radiation exposure or the relatively invasive nature of the technique. In this article, we review the proposed methods and recent advances in assessment of patients with inflammatory bowel disease; we also discuss possible strategies at the time of diagnosis, during recurrence, and in evaluation of the efficacy of drug or dietic therapy. 58 references.

  2. Enhanced Activities of Blood Thiamine Diphosphatase and Monophosphatase in Alzheimer's Disease

    PubMed Central

    Fei, Guoqiang; Jin, Lirong; Liu, Huimin; Wang, Zhiliang; Wang, Hui; Zhong, Chunjiu

    2017-01-01

    Background Thiamine metabolites and activities of thiamine-dependent enzymes are impaired in Alzheimer’s disease (AD). Objective To clarify the mechanism for the reduction of thiamine diphosphate (TDP), an active form of thiamine and critical coenzyme of glucose metabolism, in AD. Methods Forty-five AD patients clinically diagnosed and 38 age- and gender-matched control subjects without dementia were voluntarily recruited. The contents of blood TDP, thiamine monophosphate (TMP), and thiamine, as well as the activities of thiamine diphosphatase (TDPase), thiamine monophosphatase (TMPase), and thiamine pyrophosphokinase (TPK), were assayed by high performance liquid chromatography. Results Blood TDP contents of AD patients were significantly lower than those in control subjects (79.03 ± 23.24 vs. 127.60 ± 22.65 nmol/L, P<0.0001). Activities of TDPase and TMPase were significantly enhanced in AD patients than those in control subjects (TDPase: 1.24 ± 0.08 vs. 1.00 ± 0.04, P < 0.05; TMPase: 1.22 ± 0.04 vs. 1.00 ± 0.06, P < 0.01). TPK activity remained unchanged in AD as compared with that in control (0.93 ± 0.04 vs. 1.00 ± 0.04, P > 0.05). Blood TDP levels correlated negatively with TDPase activities (r = -0.2576, P = 0.0187) and positively with TPK activities (r = 0.2426, P = 0.0271) in all participants. Conclusion Enhanced TDPase and TMPase activities may contribute to the reduction of TDP level in AD patients. The results imply that an imbalance of phosphorylation-dephosphorylation related to thiamine and glucose metabolism may be a potential target for AD prevention and therapy. PMID:28060825

  3. [Importance and evidence of regular physical activity for prevention and treatment of diseases].

    PubMed

    Löllgen, H

    2013-10-01

    A sedentary lifestyle has been shown to have negative effects on morbidity and mortality. In contrast, a large number of prospective cohort studies on the effects of regular physical activity demonstrated positive effects. Therefore, physical training is today an essential part of prevention and therapy in internal medicine. This review is based on literature research in meta-analysis and review papers. Regular physical exercise or training is a significant and evidence-based part of prevention and therapy of diseases such as heart, cardiovascular and lung diseases, diabetes mellitus, renal disease and cancer. Evidence of training effects is mostly high grade. Physical activity or exercise training is indicated in many diseases as medicine--similar as a drug. It is applied after acute treatment as a component of the standard drug therapy. There is a non-linear dose-response effect, psychological aspects and some side-effects need to be considered.In conclusion, physical exercise acts as a highly efficient drug, and should be used in many diseases. Training recommendations refer to the kind, the duration, the intensity, the frequency and the increase of training.

  4. Prion-Seeding Activity Is widely Distributed in Tissues of Sporadic Creutzfeldt-Jakob Disease Patients.

    PubMed

    Takatsuki, Hanae; Fuse, Takayuki; Nakagaki, Takehiro; Mori, Tsuyoshi; Mihara, Ban; Takao, Masaki; Iwasaki, Yasushi; Yoshida, Mari; Murayama, Shigeo; Atarashi, Ryuichiro; Nishida, Noriyuki; Satoh, Katsuya

    2016-10-01

    Human prion diseases are neurodegenerative disorders caused by abnormally folded prion proteins in the central nervous system. These proteins can be detected using the quaking-induced conversion assay. Compared with other bioassays, this assay is extremely sensitive and was used in the present study to determine prion distribution in sporadic Creutzfeldt-Jakob disease patients at autopsy. Although infectivity of the sporadic form is thought to be restricted within the central nervous system, results showed that prion-seeding activities reach 10(6)/g from a 50% seeding dose in non-neuronal tissues, suggesting that prion-seeding activity exists in non-neural organs, and we suggested that non-neural tissues of 10(6)/g SD50 did not exist the infectivity.

  5. Two Analogues of Fenarimol Show Curative Activity in an Experimental Model of Chagas Disease

    PubMed Central

    2013-01-01

    Chagas disease, caused by the protozoan parasite Trypanosoma cruzi (T. cruzi), is an increasing threat to global health. Available medicines were introduced over 40 years ago, have undesirable side effects, and give equivocal results of cure in the chronic stage of the disease. We report the development of two compounds, 6 and (S)-7, with PCR-confirmed curative activity in a mouse model of established T. cruzi infection after once daily oral dosing for 20 days at 20 mg/kg 6 and 10 mg/kg (S)-7. Compounds 6 and (S)-7 have potent in vitro activity, are noncytotoxic, show no adverse effects in vivo following repeat dosing, are prepared by a short synthetic route, and have druglike properties suitable for preclinical development. PMID:24304150

  6. Serum protease activity in chronic kidney disease patients: The GANI_MED renal cohort.

    PubMed

    Wolke, Carmen; Teumer, Alexander; Endlich, Karlhans; Endlich, Nicole; Rettig, Rainer; Stracke, Sylvia; Fiene, Beate; Aymanns, Simone; Felix, Stephan B; Hannemann, Anke; Lendeckel, Uwe

    2017-03-01

    Serum or plasma proteases have been associated with various diseases including cancer, inflammation, or reno-cardiovascular diseases. We aimed to investigate whether the enzymatic activities of serum proteases are associated with the estimated glomerular filtration rate (eGFR) in patients with different stages of chronic kidney disease (CKD). Our study population comprised 268 participants of the "Greifswald Approach to Individualized Medicine" (GANI_MED) cohort. Enzymatic activity of aminopeptidase A, aminopeptidase B, alanyl (membrane) aminopeptidase, insulin-regulated aminopeptidase, puromycin-sensitive aminopeptidase, leucine aminopeptidase 3, prolyl-endopeptidase (PEP), dipeptidyl peptidase 4 (DPP4), angiotensin I-converting enzyme, and angiotensin I-converting enzyme 2 (ACE2) proteases was measured in serum. Linear regression of the respective protease was performed on kidney function adjusted for age and sex. Kidney function was modeled either by the continuous Modification of Diet in Renal Disease (MDRD)-based eGFR or dichotomized by eGFR < 15 mL/min/1.73 m(2) or <45 mL/min/1.73 m(2), respectively. Results with a false discovery rate below 0.05 were deemed statistically significant. Among the 10 proteases investigated, only the activities of ACE2 and DPP4 were correlated with eGFR. Patients with lowest eGFR exhibited highest DPP4 and ACE2 activities. DPP4 and PEP were correlated with age, but all other serum protease activities showed no associations with age or sex. Our data indicate that ACE2 and DPP4 enzymatic activity are associated with the eGFR in patients with CKD. This finding distinguishes ACE2 and DPP4 from other serum peptidases analyzed and clearly indicates that further analyses are warranted to identify the precise role of these serum ectopeptidases in the pathogenesis of CKD and to fully elucidate underlying molecular mechanisms. Impact statement • Renal and cardiac diseases are very common and often occur concomitantly

  7. Subthalamic nucleus stimulation modulates motor cortex oscillatory activity in Parkinson's disease.

    PubMed

    Devos, D; Labyt, E; Derambure, P; Bourriez, J L; Cassim, F; Reyns, N; Blond, S; Guieu, J D; Destée, A; Defebvre, L

    2004-02-01

    In Parkinson's disease, impaired motor preparation has been related to an increased latency in the appearance of movement-related desynchronization (MRD) throughout the contralateral primary sensorimotor (PSM) cortex. Internal globus pallidus (GPi) stimulation improved movement desynchronization over the PSM cortex during movement execution but failed to improve impaired motor preparation. PET studies indicate that subthalamic nucleus (STN) stimulation partly reverses the abnormal premotor pattern of brain activation during movement. By monitoring MRD, we aimed to assess changes in premotor and PSM cortex oscillatory activity induced by bilateral STN stimulation and to compare these changes with those induced by l-dopa. Ten Parkinson's disease patients and a group of healthy, age-matched controls performed self-paced wrist flexions in each of four conditions: without either stimulation or l-dopa (the 'off' condition), with stimulation and without l-dopa (On Stim), with l-dopa and without stimulation ('on drug'), and with both stimulation and l-dopa (On Both). Compared with the Off condition, in both the On Stim and the On Drug condition the Unified Parkinson's Disease Rating Scale (UPDRS) III score decreased by about 60% and in the On Both condition it decreased by 80%. The desynchronization latency over central regions contralateral to movement and the movement desynchronization over bilateral central regions were significantly increased by stimulation and by l-dopa, with a maximal effect when the two were associated. Furthermore, desynchronization latency significantly decreased over bilateral frontocentral regions in the three treatment conditions compared with the Off condition. In Parkinson's disease, STN stimulation may induce a change in abnormal cortical oscillatory activity patterns (similar to that produced by l-dopa) by decreasing the abnormal spreading of desynchronization over frontocentral regions and increasing PSM cortex activity during movement

  8. 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

  9. Pyrin Inflammasome Activation and RhoA Signaling in the Autoinflammatory Diseases FMF and HIDS

    PubMed Central

    Park, Yong Hwan; Wood, Geryl; Kastner, Daniel L.; Chae, Jae Jin

    2016-01-01

    Mutations of pyrin and mevalonate kinase (MVK) cause distinct interleukin-1β (IL-1β)-mediated autoinflammatory diseases, familial Mediterranean fever (FMF) and hyperimmunoglobulinemia D syndrome (HIDS). Pyrin forms an inflammasome when mutated or in response to bacterial modification of the GTPase RhoA. Here we show that RhoA activates the serine-threonine kinases PKN1 and PKN2 that bind and phosphorylate pyrin. Phosphorylated pyrin binds 14-3-3 proteins, which block the pyrin inflammasome. The binding of 14-3-3 and PKN proteins to FMF-associated mutant pyrin is substantially decreased, and the constitutive IL-1β release from FMF or HIDS patients’ peripheral blood mononuclear cells is attenuated by activating PKN1 and PKN2. Defects in prenylation, seen in HIDS, lead to RhoA inactivation and consequent pyrin inflammasome activation. These data indicate a previously unsuspected fundamental molecular connection between two seemingly distinct autoinflammatory disorders. PMID:27270401

  10. Utility of Consumer Physical Activity Trackers as an Intervention Tool in Cardiovascular Disease Prevention and Treatment.

    PubMed

    Hickey, Amanda M; Freedson, Patty S

    2016-01-01

    Consumer activity trackers have grown in popularity over the last few years. These devices are typically worn on the hip or wrist and provide the user with information about physical activity measures such as steps taken, energy expenditure, and time spent in moderate to vigorous physical activity. The consumer may also use the computer interface (e.g. device websites, smartphone applications) to monitor and track achievement of PA goals and compete with other users. This review will describe some of the most popular consumer devices and discuss the user feedback tools. We will also present the limited evidence available about the accuracy of these devices and highlight how they have been used in cardiovascular disease management. We conclude with some recommendations for future research, focusing on how consumer devices might be used to assess effectiveness of various cardiovascular treatments.

  11. The interplay of microRNA and neuronal activity in health and disease

    PubMed Central

    Eacker, Stephen M.; Dawson, Ted M.; Dawson, Valina L.

    2013-01-01

    MicroRNAs (miRNAs) are small 19–23 nucleotide regulatory RNAs that function by modulating mRNA translation and/or turnover in a sequence-specific fashion. In the nervous system, miRNAs regulate the production of numerous proteins involved in synaptic transmission. In turn, neuronal activity can regulate the production and turnover of miRNA through a variety of mechanisms. In this way, miRNAs and neuronal activity are in a reciprocal homeostatic relationship that balances neuronal function. The miRNA function is critical in pathological states related to overexcitation such as epilepsy and stroke, suggesting miRNA’s potential as a therapeutic target. We review the current literature relating the interplay of miRNA and neuronal activity and provide future directions for defining miRNA’s role in disease. PMID:23986658

  12. Lower physical activity is associated with higher disease burden in pediatric multiple sclerosis

    PubMed Central

    Grover, Stephanie A.; Aubert-Broche, Berengere; Fetco, Dumitru; Collins, D. Louis; Arnold, Douglas L.; Finlayson, Marcia; Banwell, Brenda L.; Motl, Robert W.

    2015-01-01

    Objective: To evaluate the association between physical activity (PA) and multiple sclerosis (MS) disease activity, depression, and fatigue in a cohort of children with MS and monophasic acquired demyelinating syndrome (mono-ADS). Methods: In this cross-sectional study of consecutive patients attending a specialized pediatric MS clinic, we administered the PedsQL Multidimensional Fatigue Scale, Center for Epidemiological Studies Depression Scale, and Godin Leisure-Time Exercise Questionnaire. Quantitative MRI analysis was performed to obtain whole brain and T2 lesion volume in a subset of participants (n = 60). Results: A total of 110 patients (79 mono-ADS; 31 MS; 5–18 years; M:F 1:1.2) were included. Patients with MS reported less strenuous (33.21 ± 31.88 metabolic equivalents [METs] vs 15.97 ± 22.73 METs, p = 0.002) and total (44.48 ± 39.35 METs vs 67.28 ± 59.65 METs; p = 0.0291) PA than those with mono-ADS. Patients with MS who reported greater amounts of moderate PA METs had fewer sleep/rest fatigue symptoms (r = −0.4). Participation in strenuous PA was associated with smaller T2 lesion volumes (r = −0.66) and lower annualized relapse rate (r = −0.66). No associations were found between total brain volume and participation in PA. Conclusions: Children with MS are less physically active than children with mono-ADS. Reasons for this are unclear, but may be related to ongoing disease activity, perceived limitations, or symptoms such as depression or fatigue. Children with MS reporting higher levels of strenuous PA had lower T2 lesion volumes and lower relapse rates, suggesting a potential protective effect of strenuous PA in this population. Further longitudinal studies are needed to establish the relationship of PA to MS symptoms and disease activity in this population. PMID:26268901

  13. Decreased glycogen synthase kinase-3 levels and activity contribute to Huntington's disease.

    PubMed

    Fernández-Nogales, Marta; Hernández, Félix; Miguez, Andrés; Alberch, Jordi; Ginés, Silvia; Pérez-Navarro, Esther; Lucas, José J

    2015-09-01

    Huntington's disease (HD) is a hereditary neurodegenerative disorder characterized by brain atrophy particularly in striatum leading to personality changes, chorea and dementia. Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase in the crossroad of many signaling pathways that is highly pleiotropic as it phosphorylates more than hundred substrates including structural, metabolic, and signaling proteins. Increased GSK-3 activity is believed to contribute to the pathogenesis of neurodegenerative diseases like Alzheimer's disease and GSK-3 inhibitors have been postulated as therapeutic agents for neurodegeneration. Regarding HD, GSK-3 inhibitors have shown beneficial effects in cell and invertebrate animal models but no evident efficacy in mouse models. Intriguingly, those studies were performed without interrogating GSK-3 level and activity in HD brain. Here we aim to explore the level and also the enzymatic activity of GSK-3 in the striatum and other less affected brain regions of HD patients and of the R6/1 mouse model to then elucidate the possible contribution of its alteration to HD pathogenesis by genetic manipulation in mice. We report a dramatic decrease in GSK-3 levels and activity in striatum and cortex of HD patients with similar results in the mouse model. Correction of the GSK-3 deficit in HD mice, by combining with transgenic mice with conditional GSK-3 expression, resulted in amelioration of their brain atrophy and behavioral motor and learning deficits. Thus, our results demonstrate that decreased brain GSK-3 contributes to HD neurological phenotype and open new therapeutic opportunities based on increasing GSK-3 activity or attenuating the harmful consequences of its decrease.

  14. Rapid inflammasome activation in microglia contributes to brain disease in HIV/AIDS

    PubMed Central

    2014-01-01

    Background Human immunodeficiency virus type 1(HIV-1) infects and activates innate immune cells in the brain resulting in inflammation and neuronal death with accompanying neurological deficits. Induction of inflammasomes causes cleavage and release of IL-1β and IL-18, representing pathogenic processes that underlie inflammatory diseases although their contribution HIV-associated brain disease is unknown. Results Investigation of inflammasome-associated genes revealed that IL-1β, IL-18 and caspase-1 were induced in brains of HIV-infected persons and detected in brain microglial cells. HIV-1 infection induced pro-IL-1β in human microglia at 4 hr post-infection with peak IL-1β release at 24 hr, which was accompanied by intracellular ASC translocation and caspase-1 activation. HIV-dependent release of IL-1β from a human macrophage cell line, THP-1, was inhibited by NLRP3 deficiency and high extracellular [K+]. Exposure of microglia to HIV-1 gp120 caused IL-1β production and similarly, HIV-1 envelope pseudotyped viral particles induced IL-1β release, unlike VSV-G pseudotyped particles. Infection of cultured feline macrophages by the related lentivirus, feline immunodeficiency virus (FIV), also resulted in the prompt induction of IL-1β. In vivo FIV infection activated multiple inflammasome-associated genes in microglia, which was accompanied by neuronal loss in cerebral cortex and neurological deficits. Multivariate analyses of data from FIV-infected and uninfected animals disclosed that IL-1β, NLRP3 and caspase-1 expression in cerebral cortex represented key molecular determinants of neurological deficits. Conclusions NLRP3 inflammasome activation was an early and integral aspect of lentivirus infection of microglia, which was associated with lentivirus-induced brain disease. Inflammasome activation in the brain might represent a potential target for therapeutic interventions in HIV/AIDS. PMID:24886384

  15. Non-exercise physical activity attenuates motor symptoms in Parkinson disease independent from nigrostriatal degeneration

    PubMed Central

    Snider, Jon; Müller, Martijn L.T.M; Kotagal, Vikas; Koeppe, Robert A; Scott, Peter J.H.; Frey, Kirk A; Albin, Roger L.; Bohnen, Nicolaas I.

    2015-01-01

    Objective To investigate the relationship between time spent in non-exercise and exercise physical activity and severity of motor functions in Parkinson disease (PD). Background Increasing motor impairments of PD incline many patients to a sedentary lifestyle. We investigated the relationship between duration of both non-exercise and exercise physical activity over a 4-week period using the Community Health Activities Model Program for Seniors (CHAMPS) questionnaire and severity of clinical motor symptoms in PD. We accounted for the magnitude of nigrostriatal degeneration. Methods Cross-sectional study. PD subjects, n=48 (40M); 69.4±7.4 (56–84) years old; 8.4±4.2 (2.5–20) years motor disease duration, mean UPDRS motor score 27.5 ± 10.3 (7–53) and mean MMSE score 28.4 ± 1.9 (22–30) underwent [11C]dihydrotetrabenazine (DTBZ) PET imaging to assess nigrostriatal denervation and completed the CHAMPS questionnaire and clinical assessment. Results Bivariate correlations showed an inverse relationship between motor UPDRS severity scores and duration of non-exercise physical activity (R= −0.37, P=0.0099) but not with duration of exercise physical activity (R= −0.05, P= 0.76) over 4 weeks. Multiple regression analysis using UPDRS motor score as outcome variable demonstrated a significant regressor effect for duration of non-exercise physical activity (F=6.15, P=0.017) while accounting for effects of nigrostriatal degeneration (F=4.93, P=0.032), levodopa-equivalent dose (LED; F=1.07, P=0.31), age (F=4.37, P=0.043) and duration of disease (F=1.46, P=0.23; total model (F=5.76, P=0.0004). Conclusions Non-exercise physical activity is a correlate of motor symptom severity in PD independent of the magnitude of nigrostriatal degeneration. Non-exercise physical activity may have positive effects on functional performance in PD. PMID:26330028

  16. 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

  17. Rheumatoid factor measured by fluoroimmunoassay: a responsive measure of rheumatoid arthritis disease activity that is associated with joint damage

    PubMed Central

    Knijff-Dutmer, E; Drossaers-Bakker, W; Verhoeven, A; van der Sluijs, Ve... G; Boers, M; van der Linden, S; van de Laar, M

    2002-01-01

    Objectives: To determine whether rheumatoid factors (RFs), measured as continuous variables by time resolved fluoroimmunoassay, reflect disease activity in rheumatoid arthritis (RA). Further, to study the association of RFs and other disease activity parameters with radiological joint damage, especially in individual patients. Methods: In active, early RA, IgM and IgA RFs, as well as erythrocyte sedimentation rate (ESR), C reactive protein (CRP), tender joint score, and swollen joint score were assessed regularly. At the study start and at 56 and 80 weeks, radiographs of hands and feet were assessed by the Sharp score (van der Heijde modification). Associations between RFs and disease activity parameters were studied. In addition, associations between radiographic damage and disease activity parameters (baseline and time integrated) were analysed by non-parametric tests and multiple regression analysis. The relation between time integrated disease activity parameters and radiological damage in individual patients was analysed and visualised. Results: 155 patients were included. RF levels were strongly associated with the disease activity parameters (especially ESR and CRP) and with each other. All disease activity parameters, at baseline as well as time integrated parameters, were associated with (the progression of) radiographic damage. Moreover, in individual patients, a linear relationship between time integrated disease activity parameters and progression of radiological damage was seen. Conclusion: RFs, measured as continuous variables, can be considered as disease activity parameters in patients with RA. The level of RF at baseline and the exposure to RF over time is associated with radiological damage. In individual patients, there is a constant relation between disease activity and radiological damage. PMID:12079900

  18. Longitudinal assessment of monocyte chemoattractant protein-1 in lupus nephritis as a biomarker of disease activity.

    PubMed

    Gupta, Ranjan; Yadav, Akhilesh; Aggarwal, Amita

    2016-11-01

    Urinary MCP-1 (uMCP-1) levels reflect lupus nephritis (LN) disease activity. However, long-term prospective studies evaluating it as a biomarker are lacking. SLE patients with active nephritis (AN), active disease without nephritis (ANR), and inactive disease (ID) were enrolled. AN patients were followed up every 3 months for 1 year. Urine and serum samples were collected at baseline from all and at follow-up visits in AN group. Urine samples from healthy subjects (HC), rheumatoid arthritis (RA), and diabetic nephropathy (DM) patients (20 each) served as controls. Serum (sMCP-1) and uMCP-1 was measured using ELISA. Urinary values were normalized for creatinine excretion. Nonparametric tests were used. A total of 121 SLE patients were enrolled. Baseline uMCP-1 was significantly higher in AN as compared to ANR, ID, HC, and RA (p < 0.001), but it was not different from DM and showed good correlation with rSLEDAI and SLEDAI (r = 0.52 and 0.47, p < 0.001) but not with sMCP-1. On ROC analysis to differentiate between AN and ANR, uMCP-1 performed better than sMCP-1, anti-dsDNA antibodies, C3 and C4. uMCP-1 and not sMCP-1 decreased significantly at all follow-up visits (p < 0.001). uMCP-1 remained persistently elevated in a patient who developed CKD and rose before conventional markers in two patients with relapse of LN. uMCP-1 correlates well with LN disease activity and helps differentiate between AN and ANR patients. Its levels fall with treatment and may have a potential to predict poor response and relapse of LN. uMCP-1 is most likely generated locally in the kidney.

  19. 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.

  20. Relation of physical activity to prevalence of nonalcoholic Fatty liver disease independent of cardiometabolic risk.

    PubMed

    Oni, Ebenezer T; Kalathiya, Rohan; Aneni, Ehimen C; Martin, Seth S; Blaha, Michael J; Feldman, Theodore; Agatston, Arthur S; Blumenthal, Roger S; Conceiçao, Raquel D; Carvalho, Jose A M; Santos, Raul D; Nasir, Khurram

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is associated with obesity and insulin resistance and has been linked with increased cardiovascular risk. Although physical activity (PA) and lifestyle modification are often recommended in patients at cardiovascular risk, the benefit across the cardiometabolic risk spectrum is unclear. We aimed to evaluate the relation of PA and NAFLD independent of metabolic syndrome (MS) or obesity. We evaluated 5,743 healthy Brazilian subjects (43 ± 10 years, 79% men) without clinical coronary heart disease from December 2008 to December 2010. NAFLD was diagnosed using ultrasounds, and self-reported PA was assessed using the International Physical Activity Questionnaire scale. In a multivariate logistic regression adjusted for cardiometabolic risk factors, we evaluated for an independent association of NAFLD and PA. In the total study population, NAFLD prevalence was 36% (n = 2,075), obesity 23% (1,300), and MS 20% (1,152). NAFLD was more prevalent in subjects with MS (74%) than those without (26%) and in those obese (73%) than in those nonobese (25%). Overall, 1,305 (23%) subjects reported low activity, 1,990 (35%) moderate activity, and 2,448 (42%) high activity. NAFLD prevalence was lower at higher levels of reported PA (low 45%, moderate 38%, and high 30%, p <0.001). After adjusting for risk factors, subjects with high activity had lower odds of having NAFLD. The favorable association was independent of obesity or MS. In conclusion, PA presents a dose-response association with NAFLD independent of the MS or obesity. Our results are compatible with the idea that benefits of PA are relevant to everyone regardless of cardiometabolic risk.

  1. [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.

  2. Recent Trends in Pharmacological Activity of Alkaloids in Animal Colitis: Potential Use for Inflammatory Bowel Disease

    PubMed Central

    Souza-Brito, Alba Regina Monteiro; Luiz-Ferreira, Anderson

    2017-01-01

    Inflammatory bowel disease (IBD) is a chronic and disrupted inflammation of the gastrointestinal tract. IBD have two main conditions, Crohn's disease and ulcerative colitis, and have been extensively investigated in recent years. Antibiotics derived from salicylates, steroids, immunosuppressors, and anti-TNF therapy are part of the therapeutic arsenal for IBD. However, very often patients stop responding to treatments over the time. In this context, searching for alternative agents is crucial for IBD clinical management. Natural products derived from medicinal plants are an interesting therapeutic alternative, since several studies have proven effective treatments in animal models of intestinal inflammation. Several naturally occurring compounds are potent antioxidants, both as free radical scavengers and as modulators of antioxidant enzymes expression and activity. A number of natural compounds have also been proved to inhibit the release of proinflammatory cytokines, decreasing the activation of nuclear factor κB (NF-κB), which is important to the inflammatory response in IBD. The alkaloids are substances of a very diverse class of plant secondary metabolites; an extensive list of biological activities has been attributed to alkaloids, such as being anticholinergic, antitumor, diuretic, antiviral, antihypertensive, antiulcer, analgesic, and anti-inflammatory. In the present work, studies on the pharmacological activity of alkaloids in experimental models of IBD were reviewed. PMID:28191024

  3. Endothelin A receptor activation on mesangial cells initiates Alport glomerular disease.

    PubMed

    Dufek, Brianna; Meehan, Daniel T; Delimont, Duane; Cheung, Linda; Gratton, Michael Anne; Phillips, Grady; Song, Wenping; Liu, Shiguang; Cosgrove, Dominic

    2016-08-01

    Recent work demonstrates that Alport glomerular disease is mediated through a biomechanical strain-sensitive activation of mesangial actin dynamics. This occurs through a Rac1/CDC42 cross-talk mechanism that results in the invasion of the subcapillary spaces by mesangial filopodia. The filopodia deposit mesangial matrix proteins in the glomerular basement membrane, including laminin 211, which activates focal adhesion kinase in podocytes culminating in the up-regulation of proinflammatory cytokines and metalloproteinases. These events drive the progression of glomerulonephritis. Here we test whether endothelial cell-derived endothelin-1 is up-regulated in Alport glomeruli and further elevated by hypertension. Treatment of cultured mesangial cells with endothelin-1 activates the formation of drebrin-positive actin microspikes. These microspikes do not form when cells are treated with the endothelin A receptor antagonist sitaxentan or under conditions of small, interfering RNA knockdown of endothelin A receptor mRNA. Treatment of Alport mice with sitaxentan results in delayed onset of proteinuria, normalized glomerular basement membrane morphology, inhibition of mesangial filopodial invasion of the glomerular capillaries, normalization of glomerular expression of metalloproteinases and proinflammatory cytokines, increased life span, and prevention of glomerulosclerosis and interstitial fibrosis. Thus endothelin A receptor activation on mesangial cells is a key event in initiation of Alport glomerular disease in this model.

  4. Antimicrobial activity of metal based nanoparticles against microbes associated with diseases in aquaculture.

    PubMed

    Swain, P; Nayak, S K; Sasmal, A; Behera, T; Barik, S K; Swain, S K; Mishra, S S; Sen, A K; Das, J K; Jayasankar, P

    2014-09-01

    The emergence of diseases and mortalities in aquaculture and development of antibiotics resistance in aquatic microbes, has renewed a great interest towards alternative methods of prevention and control of diseases. Nanoparticles have enormous potential in controlling human and animal pathogens and have scope of application in aquaculture. The present investigation was carried out to find out suitable nanoparticles having antimicrobial effect against aquatic microbes. Different commercial as well as laboratory synthesized metal and metal oxide nanoparticles were screened for their antimicrobial activities against a wide range of bacterial and fungal agents including certain freshwater cyanobacteria. Among different nanoparticles, synthesized copper oxide (CuO), zinc oxide (ZnO), silver (Ag) and silver doped titanium dioxide (Ag-TiO2) showed broad spectrum antibacterial activity. On the contrary, nanoparticles like Zn and ZnO showed antifungal activity against fungi like Penicillium and Mucor species. Since CuO, ZnO and Ag nanoparticles showed higher antimicrobial activity, they may be explored for aquaculture use.

  5. Risk of decline in functional activities in dementia with Lewy bodies and Alzheimer disease.

    PubMed

    Gill, Dawn P; Koepsell, Thomas D; Hubbard, Rebecca A; Kukull, Walter A

    2011-01-01

    We examined the risk of 1-year decline in 4 everyday activities in patients with dementia with Lewy bodies (DLB), relative to patients with Alzheimer disease (AD). Data were from the National Alzheimer's Coordinating Center, gathered from 32 Alzheimer's Disease Centers. Participants (n=1880) were: aged 60+ years, demented with a primary clinical diagnosis of probable AD or DLB, and had a global Clinical Dementia Rating of 0.5 to 2. The activities were measured with the Functional Activities Questionnaire. In modified Poisson regression models adjusted for demographics, baseline activity, years from symptom onset, cognitive impairment, and comorbidities; DLB participants aged 67 to 81 years had 1.5 to 2 times increased risk of decline in performing basic kitchen tasks, engaging in games/hobbies, and paying attention/understanding, relative to AD participants of the same age (P<0.05). There was no significant difference between AD and DLB participants beyond this age range. For decline in ability to go shopping alone, there was also no significant difference between AD and DLB participants. In summary, the functional course of DLB, relative to AD, may depend on the age of the patient. These findings may provide anticipatory guidance to families and healthcare providers, which may be useful in the planning of care strategies.

  6. A correlation of pregnancy term, disease activity, serum female hormones, and cytokines in uveitis

    PubMed Central

    Chan, C-C; Reed, G F; Kim, Y; Agrón, E; Buggage, R R

    2004-01-01

    Background/aims: Pregnancy and the postpartum period are associated with the activity of autoimmune diseases including uveitis. Although the exact mechanism is unknown, hormones are reported to alter inflammatory cytokines and influence disease activity. The authors studied ocular inflammation, female hormones, and serum cytokine levels during and after pregnancy. Methods: A prospective, observational case study was conducted. Four pregnant women in their first trimester with chronic non-infectious uveitis were followed monthly until 6 months after delivery. Serum female hormones (oestrogen, progesterone, prolactin) and various cytokines (IL-2, IL-4, IL-5, IL-6, IL-10, IFN-γ, and TGF-β) were measured by ELISA. Results: The four patients had five full term pregnancies. Uveitis activity decreased after the first trimester but flared in the early postpartum period. Serum female hormones, highly elevated during pregnancy, drastically dropped post partum. Cytokine levels except TGF-β were mostly undetectable. Conclusion: Female hormones and TGF-β may contribute to the activity of uveitis during pregnancy and the postpartum period. PMID:15548800

  7. Laboratory aspects of von Willebrand disease: test repertoire and options for activity assays and genetic analysis.

    PubMed

    Castaman, G; Hillarp, A; Goodeve, A

    2014-05-01

    The deficiency or abnormal function of von Willebrand factor (VWF) causes von Willebrand disease (VWD), the most frequent inherited bleeding disorder. The laboratory diagnosis of VWD can be difficult as the disease is heterogeneous and an array of assays is required to describe the phenotype. Basic classification of quantitative (type 1 and 3) and qualitative (type 2) VWD variants requires determination of VWF antigenic (VWF:Ag) levels and assaying of VWF ristocetin cofactor (VWF:RCo) activity, determining the capacity of VWF to interact with the platelet GPIb-receptor. Knowing the VWF:RCo activity is essential for identifying, subtyping and monitoring VWD, but the assay is poorly standardized and many protocols do not fulfil the clinical need in all situations. This has led to the development of novel activity assays, independent of ristocetin, with enhanced assay characteristics. Results from the first independent clinical evaluations are promising, showing that they are reliable and suitable for VWD diagnosis. The qualitative type 2 VWF deficiency can be further divided into four different subtypes (A, B, M and N) using specific assays that explore other activities or the size distribution of VWF multimers. These methods are discussed herein. However, in a number of patients it may be difficult to correctly classify the VWD phenotype and genetic analysis may provide the best option to clarify the disorder, through mutation identification.

  8. S100B is a potential disease activity marker in non-segmental vitiligo.

    PubMed

    Speeckaert, Reinhart; Voet, Sofie; Hoste, Esther; van Geel, Nanja

    2017-02-14

    Vitiligo is a chronic skin condition characterized by progressive depigmentation of the skin. S100B is a damage-associated molecular pattern (DAMP) protein expressed in melanocytes, which has been proposed as a marker of melanocyte cytotoxicity. While the use of S100B as a biomarker in melanoma is well established, its association with vitiligo activity has not yet been investigated. Here, we show that S100B serum levels were significantly increased in patients with active non-segmental vitiligo and strongly correlated with the affected body surface area. Prospective follow-up showed a predictive value of serum S100B levels on disease progression. In vitro experiments using repeated freeze-thaw procedures demonstrated an intracellular upregulation of S100B in normal and vitiligo melanocytes prior to an extensive release in the environment. This phenomenon may explain the increased S100B serum values in the active phase of vitiligo. In a monobenzone-induced vitiligo mouse model we could show the potential of S100B inhibition as a therapeutic strategy in vitiligo. In conclusion, this report demonstrates the possible use of S100B as a biomarker for disease activity in vitiligo. Our data suggest that this DAMP protein could play a substantial role in the pathogenesis of vitiligo and may be a potential new target for treatment.

  9. 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.

  10. MACVIA-LR (Fighting Chronic Diseases for Active and Healthy Ageing in Languedoc-Roussillon): A Success Story of the European Innovation Partnership on Active and Healthy Ageing.

    PubMed

    Bousquet, J; Bourret, R; Camuzat, T; Augé, P; Bringer, J; Noguès, M; Jonquet, O; de la Coussaye, J E; Ankri, J; Cesari, M; Guérin, O; Vellas, B; Blain, H; Arnavielhe, S; Avignon, A; Combe, B; Canovas, G; Daien, C; Dray, G; Dupeyron, A; Jeandel, C; Laffont, I; Laune, D; Marion, C; Pastor, E; Pélissier, J Y; Galan, B; Reynes, J; Reuzeau, J C; Bedbrook, A; Granier, S; Adnet, P A; Amouyal, M; Alomène, B; Bernard, P L; Berr, C; Caimmi, D; Claret, P G; Costa, D J; Cristol, J P; Fesler, P; Hève, D; Millot-Keurinck, J; Morquin, D; Ninot, G; Picot, M C; Raffort, N; Roubille, F; Sultan, A; Touchon, J; Attalin, V; Azevedo, C; Badin, M; Bakhti, K; Bardy, B; Battesti, M P; Bobia, X; Boegner, C; Boichot, S; Bonnin, H Y; Bouly, S; Boubakri, C; Bourrain, J L; Bourrel, G; Bouix, V; Bruguière, V; Cade, S; Camu, W; Carre, V; Cavalli, G; Cayla, G; Chiron, R; Coignard, P; Coroian, F; Costa, P; Cottalorda, J; Coulet, B; Coupet, A L; Courrouy-Michel, M C; Courtet, P; Cros, V; Cuisinier, F; Danko, M; Dauenhauer, P; Dauzat, M; David, M; Davy, J M; Delignières, D; Demoly, P; Desplan, J; Dujols, P; Dupeyron, G; Engberink, O; Enjalbert, M; Fattal, C; Fernandes, J; Fouletier, M; Fraisse, P; Gabrion, P; Gellerat-Rogier, M; Gelis, A; Genis, C; Giraudeau, N; Goucham, A Y; Gouzi, F; Gressard, F; Gris, J C; Guillot, B; Guiraud, D; Handweiler, V; Hayot, M; Hérisson, C; Heroum, C; Hoa, D; Jacquemin, S; Jaber, S; Jakovenko, D; Jorgensen, C; Kouyoudjian, P; Lamoureux, R; Landreau, L; Lapierre, M; Larrey, D; Laurent, C; Léglise, M S; Lemaitre, J M; Le Quellec, A; Leclercq, F; Lehmann, S; Lognos, B; Lussert, Cj M; Makinson, A; Mandrick, K; Mares, P; Martin-Gousset, P; Matheron, A; Mathieu, G; Meissonnier, M; Mercier, G; Messner, P; Meunier, C; Mondain, M; Morales, R; Morel, J; Mottet, D; Nérin, P; Nicolas, P; Nouvel, F; Paccard, D; Pandraud, G; Pasdelou, M P; Pasquié, J L; Patte, K; Perrey, S; Pers, Y M; Portejoie, F; Pujol, J L E; Quantin, X; Quéré, I; Ramdani, S; Ribstein, J; Rédini-Martinez, I; Richard, S; Ritchie, K; Riso, J P; Rivier, F; Robine, J M; Rolland, C; Royère, E; Sablot, D; Savy, J L; Schifano, L; Senesse, P; Sicard, R; Stephan, Y; Strubel, D; Tallon, G; Tanfin, M; Tassery, H; Tavares, I; Torre, K; Tribout, V; Uziel, A; Van de Perre, P; Venail, F; Vergne-Richard, C; Vergotte, G; Vian, L; Vialla, F; Viart, F; Villain, M; Viollet, E; Ychou, M; Mercier, J

    2016-01-01

    The Région Languedoc Roussillon is the umbrella organisation for an interconnected and integrated project on active and healthy ageing (AHA). It covers the 3 pillars of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA): (A) Prevention and health promotion, (B) Care and cure, (C) and (D) Active and independent living of elderly people. All sub-activities (poly-pharmacy, falls prevention initiative, prevention of frailty, chronic respiratory diseases, chronic diseases with multimorbidities, chronic infectious diseases, active and independent living and disability) have been included in MACVIA-LR which has a strong political commitment and involves all stakeholders (public, private, patients, policy makers) including CARSAT-LR and the Eurobiomed cluster. It is a Reference Site of the EIP on AHA. The framework of MACVIA-LR has the vision that the prevention and management of chronic diseases is essential for the promotion of AHA and for the reduction of handicap. The main objectives of MACVIA-LR are: (i) to develop innovative solutions for a network of Living labs in order to reduce avoidable hospitalisations and loss of autonomy while improving quality of life, (ii) to disseminate the innovation. The three years of MACVIA-LR activities are reported in this paper.

  11. Asymptomatic Atherosclerosis in Egyptian Rheumatoid Arthritis Patients and Its Relation to Disease Activity

    PubMed Central

    Elshereef, Rawhya R.; Darwish, Aymen; Ali, Amal; Abdel-kadar, Mohammed; Hamdy, Lamiaa

    2015-01-01

    Aim. To detect the frequency of subclinical atherosclerosis in rheumatoid arthritis patients without clinically evident atherosclerosis and to correlate its presence with the disease activity. Patients and Methods. Our study includes 112 RA patients (group 1) and 40 healthy controls (group 11). All patients and controls were subjected to full history taking, clinical examination, and laboratory investigations. Carotid intima media wall thickness (IMT) and carotid plaques were measured in both groups by B-mode ultrasonography; also color duplex Doppler ultrasound of the brachial artery was done to detect endothelial function. Results. There is atherosclerosis in 31.3% of asymptomatic RA patients compared with only 5% in controls (P = 0.003**). A significant difference was detected in patients with and without atherosclerosis regarding duration of the disease (P = 0.0001***) and patient's age (P = 0.01*). There is highly statistical significant correlation between atherosclerosis and disease activity index. Conclusion. The frequency of subclinical atherosclerosis was high in long-term active RA patients. PMID:25737726

  12. 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.

  13. Constitutive activity of G-protein-coupled receptors: cause of disease and common property of wild-type receptors.

    PubMed

    Seifert, Roland; Wenzel-Seifert, Katharina

    2002-11-01

    The aim of this review is to provide a systematic overview on constitutively active G-protein-coupled receptors (GPCRs), a rapidly evolving area in signal transduction research. We will discuss mechanisms, pharmacological tools and methodological approaches to analyze constitutive activity. The two-state model defines constitutive activity as the ability of a GPCR to undergo agonist-independent isomerization from an inactive (R) state to an active (R*) state. While the two-state model explains basic concepts of constitutive GPCR activity and inverse agonism, there is increasing evidence for multiple active GPCR conformations with distinct biological activities. As a result of constitutive GPCR activity, basal G-protein activity increases. Until now, constitutive activity has been observed for more than 60 wild-type GPCRs from the families 1-3 and from different species including humans and commonly used laboratory animal species. Additionally, several naturally occurring and disease-causing GPCR mutants with increased constitutive activity relative to wild-type GPCRs have been identified. Alternative splicing, RNA editing, polymorphisms within a given species, species variants and coupling to specific G-proteins all modulate the constitutive activity of GPCRs, providing multiple regulatory switches to fine-tune basal cellular activities. The most important pharmacological tools to analyze constitutive activity are inverse agonists and Na(+) that stabilize the R state, and pertussis toxin that uncouples GPCRs from G(i)/G(o)-proteins. Constitutive activity is observed at low and high GPCR expression levels, in native systems and in recombinant systems, and has been reported for GPCRs coupled to G(s)-, G(i)- and G(q)-proteins. Constitutive activity of neurotransmitter GPCRs may provide a tonic support for basal neuronal activity. For the majority of GPCRs known to be constitutively active, inverse agonists have already been identified. Inverse agonists may be useful

  14. Macrophage Activation Syndrome Associated with Adult-Onset Still's Disease Successfully Treated with Anakinra

    PubMed Central

    Kato, Hiroshi

    2016-01-01

    Macrophage activation syndrome (MAS) is a potentially fatal complication of Adult-Onset Still's disease (Still's disease). Whereas an increasing body of evidence supports interleukin-1 (IL-1) blockade as a promising treatment for Still's disease, whether it is therapeutic for MAS associated with Still's disease remains unclear. We report a 34-year-old Caucasian man with one-decade history of TNF-blockade-responsive seronegative arthritis who presented with abrupt onset of fever, serositis, bicytopenia, splenomegaly, hepatitis, and disseminated intravascular coagulation. Striking hyperferritinemia was noted without evidence of infection, malignancy, or hemophagocytosis on bone marrow biopsy. NK cells were undetectable in the peripheral blood, whereas soluble IL-2 receptor was elevated. His multiorgan disease resolved in association with methylprednisolone pulse therapy, Anakinra, and a tapering course of prednisone. This case reinforces the notion that Still's disease is inherently poised to manifest MAS as one of the clinical phenotypes by shedding light on the role of IL-1 underlying both Still's disease and related MAS. PMID:27818826

  15. Activation detector

    DOEpatents

    Bell, Zane William [Oak Ridge, TN; Boatner, Lynn Allen [Oak Ridge, TN

    2009-12-08

    A method of detecting an activator, the method including impinging with an activator a receptor material lacking a photoluminescent material and generating a by-product of a radioactive decay due to the activator impinging the reeptor material. The method further including, generating light from the by-product via the Cherenkov effect and identifying a characteristic of the activator based on the light.

  16. Motor imagery evokes increased somatosensory activity in Parkinson's disease patients with tremor.

    PubMed

    Helmich, Rick C; Bloem, Bastiaan R; Toni, Ivan

    2012-08-01

    Parkinson's disease (PD) is surprisingly heterogeneous: some patients have a prominent resting tremor, while others never develop this symptom. Here we investigate whether the functional organization of the voluntary motor system differs between PD patients with and without resting tremor, and whether these differences relate to the cerebral circuit producing tremor. We compared 18 PD patients with marked tremor, 20 PD patients without tremor, and 19 healthy controls. Subjects performed a controlled motor imagery task during fMRI scanning. We quantified imagery-related cerebral activity by contrasting imagery of biomechanically difficult and easy movements. Tremor-related activity was identified by relating cerebral activity to fluctuations in tremor amplitude, using electromyography during scanning. PD patients with tremor had better behavioral performance than PD patients without tremor. Furthermore, tremulous PD patients showed increased imagery-related activity in somatosensory area 3a, as compared with both healthy controls and to nontremor PD patients. This effect was independent from tremor-related activity, which was localized to the motor cortex, cerebellum, and thalamic ventral intermediate nucleus (VIM). The VIM, with known projections to area 3a, was unique in showing both tremor- and imagery-related responses. We conclude that parkinsonian tremor influences motor imagery by modulating central somatosensory processing through the VIM. This mechanism may explain clinical differences between PD patients with and without tremor.

  17. Clinical criteria for the assessment of disease activity in Graves' ophthalmopathy: a novel approach.

    PubMed Central

    Mourits, M P; Koornneef, L; Wiersinga, W M; Prummel, M F; Berghout, A; van der Gaag, R

    1989-01-01

    Patients with serious inflammatory Graves' ophthalmopathy should be treated with anti-inflammatory drugs or radiotherapy to prevent complications like fibrosis, while those with non-inflammatory ophthalmopathy may be treated by surgery immediately. It is often difficult, however, to distinguish inflammatory from non-inflammatory Graves' disease. We therefore present a simple clinical classification here to differentiate between these two conditions. This classification is based on the classical signs of inflammation--pain, redness, swelling, and impaired function. After two consecutive clinical examinations an 'activity score' can be determined, ranging from 0 to 10 points. In a retrospective study testing the efficacy of this classification we found that patients with an activity score of 3 or more at the beginning of therapy responded well to anti-inflammatory drugs, while those with a lower activity score mostly did not. Comparing the pretreatment activity score with the degree of enlargement of the extraocular muscles on the CT scan, we found a significant correlation between these two parameters: the higher the activity score, the more the enlargement of the muscles. We conclude that this classification facilitates the proper selection of patients for treatment. Images PMID:2765444

  18. Comparison of oscillatory activity in subthalamic nucleus in Parkinson's disease and dystonia

    PubMed Central

    Jiang, Yin; Ashkan, Keyoumars; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Green, Alexander; Aziz, Tipu; Brown, Peter; Wang, Shouyan

    2017-01-01

    Objectives Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been successfully used to treat both Parkinson's disease (PD) and dystonia. Local field potentials (LFPs) recorded from the STN of PD patients demonstrate prominent beta frequency band activity. It is unclear whether such activity occurs in the STN in dystonia, and, if not, whether dystonia has another distinctive neural population activity in the STN. Methods Twelve patients with PD, and eight patients with dystonia underwent DBS electrode implantation targeting the STN. Seven dystonia patients were off medication and one was on aripiprazole and clonazepam. LFPs were recorded from the DBS electrodes in PD in the on/off medication states and in dystonia. Power spectra and temporal dynamics measured by the with Lempel-Ziv complexity of the LFPs were compared among these states. Results Normalised power spectra and Lempel-Ziv complexity of subthalamic LFPs differed between dystonia off and PD on/off, and between PD off and on over the low frequency, beta and high gamma bands. Patients with dystonia and off medication had lower beta power but higher low frequency and high gamma power than PD. Spectral power in the low beta frequency (11–20 Hz) range was attenuated in medicated PD. Conclusion The results suggest that dystonia and PD are characterized by different patterns of oscillatory activities even within the same nucleus, and exaggerated beta activity may relate to hypo-dopaminergic status. PMID:27940307

  19. Danger signals activating innate immunity in graft-versus-host disease.

    PubMed

    Zeiser, Robert; Penack, Olaf; Holler, Ernst; Idzko, Marco

    2011-09-01

    Extensive cell death with consecutive release of danger signals can cause immune-mediated tissue destruction. The abundance of cell death is likely to determine the relevance of the danger signals as physiological mechanisms that counteract immune activation may be overruled. Such constellation is conceivable in chemo-/radiotherapy-induced tissue damage, reperfusion injury, trauma, and severe infection. Studies on graft-versus-host disease (GvHD) development have to consider the effects of chemo-/radiotherapy-related tissue damage leading to the release of exogenous and endogenous danger signals. Our previous work has demonstrated a role for adenosine-5'-triphosphate (ATP) as an endogenous danger signal in GvHD. Besides ATP, uric acid or soluble extracellular matrix components are functional danger signals that activate the NLRP3 inflammasome when released from dying cells or from extracellular matrix. In contrast to sterile inflammation, GvHD is more complex since bacterial components that leak through damaged intestinal barriers and the skin can activate pattern recognition receptors and directly contribute to GvHD pathogenesis. These exogenous danger signals transmit immune activation via toll-like receptors and NOD-like receptors of the innate immune system. This review covers both the impact of endogenous and exogenous danger signals activating innate immunity in GvHD.

  20. Neuroanatomic substrates of semantic memory impairment in Alzheimer’s disease: Patterns of functional MRI activation

    PubMed Central

    SAYKIN, ANDREW J.; FLASHMAN, LAURA A.; FRUTIGER, SALLY A.; JOHNSON, STERLING C.; MAMOURIAN, ALEXANDER C.; MORITZ, CHAD H.; O’JILE, JUDITH R.; RIORDAN, HENRY J.; SANTULLI, ROBERT B.; SMITH, CYNTHIA A.; WEAVER, JOHN B.

    2015-01-01

    Impairment in semantic processing occurs early in Alzheimer’s disease (AD) and differential impact on subtypes of semantic relations have been reported, yet there is little data on the neuroanatomic basis of these deficits. Patients with mild AD and healthy controls underwent 3 functional MRI auditory stimulation tasks requiring semantic or phonological decisions (match–mismatch) about word pairs (category–exemplar, category–function, pseudoword). Patients showed a significant performance deficit only on the exemplar task. On voxel-based fMRI activation analyses, controls showed a clear activation focus in the left superior temporal gyrus for the phonological task; patients showed additional foci in the left dorsolateral prefrontal and bilateral cingulate areas. On the semantic tasks, predominant activation foci were seen in the inferior and middle frontal gyrus (left greater than right) in both groups but patients showed additional activation suggesting compensatory recruitment of locally expanded foci and remote regions, for example, right frontal activation during the exemplar task. Covariance analyses indicated that exemplar task performance was strongly related to signal increase in bilateral medial prefrontal cortex. The authors conclude that fMRI can reveal similarities and differences in functional neuroanatomical processing of semantic and phonological information in mild AD compared to healthy elderly, and can help to bridge cognitive and neural investigations of the integrity of semantic networks in AD. PMID:10439584

  1. NF-κB activity is inversely correlated to RNF11 expression in Parkinson's disease.

    PubMed

    Pranski, Elaine; Van Sanford, Carson D; Dalal, Nirjari; Orr, Adam L; Karmali, Dipan; Cooper, Deborah S; Gearing, Marla; Lah, James J; Levey, Allan I; Betarbet, Ranjita

    2013-06-28

    RING finger protein 11 (RNF11), a negative regulator of NF-κB signaling pathway, colocalizes with α-synuclein and is sequestered in Lewy bodies in Parkinson's disease (PD). Since persistent NF-κB activation is reported in PD, in this report we investigated if RNF11 expression level is correlated to activated NF-κB in PD. We examined RNF11 expression levels in correlation to phospho-p65, a marker for activated NF-κB, in control and PD brain tissue from cerebral cortex. In addition we performed double immunofluorescence labeling experiments to confirm this correlation. Our investigations demonstrated that the neuronal RNF11 expression was down-regulated in PD and was usually associated with increased expression of phospho-p65. Double labeling confirmed that loss of neuronal RNF11 was linked to increased phospho-p65 expression, suggesting that persistent presence of NF-κB activation could be due to decreased levels of its negative regulator. Our data exemplifies the relevance of RNF11 and persistent NF-κB activation in PD.

  2. Disease-modifying therapeutic concepts for HIV in the era of highly active antiretroviral therapy.

    PubMed

    Butler, Scott L; Valdez, Hernan; Westby, Michael; Perros, Manos; June, Carl H; Jacobson, Jeffrey M; Levy, Yves; Cooper, David A; Douek, Daniel; Lederman, Michael M; Tebas, Pablo

    2011-11-01

    Chronic HIV infection is associated with persistent immune activation and inflammation even among patients virologically suppressed on antiretroviral therapy for years. Chronic immune activation has been associated with poor outcomes--both AIDS-defining and non-AIDS-defining clinical events--and persistent CD4 T-cell depletion. The cause of chronic immune activation in well-controlled HIV infection is unknown. Proposed drivers include residual viral replication, microbial translocation, and coinfecting pathogens. Therapeutic interventions targeting immune activation are emerging, from approaches that interfere directly with activation and inflammatory pathways to those that prevent microbial translocation or decrease the availability of host target cells for the virus. In the context of the disappointing results of the interleukin-2 trials, the main challenges to developing these disease-modifying therapies include identifying an adequate target population and choosing surrogate endpoints that will provide positive proof-of-concept that the interventions will translate into long-term clinical benefit before embarking on large clinical endpoint trials.

  3. Mitogen-activated Tasmanian devil blood mononuclear cells kill devil facial tumour disease cells.

    PubMed

    Brown, Gabriella K; Tovar, Cesar; Cooray, Anne A; Kreiss, Alexandre; Darby, Jocelyn; Murphy, James M; Corcoran, Lynn M; Bettiol, Silvana S; Lyons, A Bruce; Woods, Gregory M

    2016-08-01

    Devil facial tumour disease (DFTD) is a transmissible cancer that has brought the host species, the Tasmanian devil, to the brink of extinction. The cancer cells avoid allogeneic immune recognition by downregulating cell surface major histocompatibility complex (MHC) I expression. This should prevent CD8(+) T cell, but not natural killer (NK) cell, cytotoxicity. The reason why NK cells, normally reactive to MHC-negative cells, are not activated to kill DFTD cells has not been determined. The immune response of wild devils to DFTD, if it occurs, is uncharacterised. To investigate this, we tested 12 wild devils with DFTD, and found suggestive evidence of low levels of antibodies against DFTD cells in one devil. Eight of these devils were also analysed for cytotoxicity, however, none showed evidence for cytotoxicity against cultured DFTD cells. To establish whether mimicking activation of antitumour responses could induce cytotoxic activity against DFTD, Tasmanian devil peripheral blood mononuclear cells (PBMCs) were treated with either the mitogen Concanavalin A, the Toll-like receptor agonist polyinosinic:polycytidylic acid or recombinant Tasmanian devil IL-2. All induced the PBMC cells to kill cultured DFTD cells, suggesting that activation does not occur after encounter with DFTD cells in vivo, but can be induced. The identification of agents that activate cytotoxicity against DFTD target cells is critical for developing strategies to protect against DFTD. Such agents could function as adjuvants to induce functional immune responses capable of targeting DFTD cells and tumours in vivo.

  4. Lateralization of brain activity pattern during unilateral movement in Parkinson's disease.

    PubMed

    Wu, Tao; Hou, Yanan; Hallett, Mark; Zhang, Jiarong; Chan, Piu

    2015-05-01

    We investigated the lateralization of brain activity pattern during performance of unilateral movement in drug-naïve Parkinson's disease (PD) patients with only right hemiparkinsonian symptoms. Functional MRI was obtained when the subjects performed strictly unilateral right hand movement. A laterality index was calculated to examine the lateralization. Patients had decreased activity in the left putamen and left supplementary motor area, but had increased activity in the right primary motor cortex, right premotor cortex, left postcentral gyrus, and bilateral cerebellum. The laterality index was significantly decreased in PD patients compared with controls (0.41 ± 0.14 vs. 0.84 ± 0.09). The connectivity from the left putamen to cortical motor regions and cerebellum was decreased, while the interactions between the cortical motor regions, cerebellum, and right putamen were increased. Our study demonstrates that in early PD, the lateralization of brain activity during unilateral movement is significantly reduced. The dysfunction of the striatum-cortical circuit, decreased transcallosal inhibition, and compensatory efforts from cortical motor regions, cerebellum, and the less affected striatum are likely reasons contributing to the reduced motor lateralization. The disruption of the lateralized brain activity pattern might be a reason underlying some motor deficits in PD, like mirror movements or impaired bilateral motor coordination.

  5. Active Aging for Individuals with Parkinson's Disease: Definitions, Literature Review, and Models

    PubMed Central

    Lökk, Johan

    2014-01-01

    Active aging has been emerged to optimize different aspects of health opportunities during the aging process in order to enhance quality of life. Yet, most of the efforts are on normal aging and less attention has been paid for the elderly suffering from a chronic illness such as Parkinson's disease (PD). The aim of this review was to investigate how the concept of “active aging” fit for the elderly with PD and to propose a new model for them using the recent improvements in caring models and management approaches. For this purpose, biomedical databases have been assessed using relevant keywords to find out appropriate articles. Movement problems of PD affect physical activity, psychiatric symptoms lessen social communication, and cognitive impairment could worsen mental well-being in elderly with PD, all of which could lead to earlier retirement and poorer quality of life compared with healthy elderly. Based on the multisystematic nature of PD, a new “Active Aging Model for Parkinson's Disease” is proposed consisting of self-care, multidisciplinary and interdisciplinary care, palliative care, patient-centered care, and personalized care. These strategies could potentially help the individuals with PD to have a better management approach for their condition towards the concept of active aging. PMID:25225618

  6. Differences in brain activation between tremor- and nontremor-dominant Parkinson disease.

    PubMed

    Prodoehl, Janey; Planetta, Peggy J; Kurani, Ajay S; Comella, Cynthia L; Corcos, Daniel M; Vaillancourt, David E

    2013-01-01

    OBJECTIVE To compare differences in functional brain activity between tremor- and nontremor-dominant subtypes of Parkinson disease (PD) using functional magnetic resonance imaging. DESIGN In our study, patients with tremor-dominant PD and those with nontremor-dominant PD performed a grip task, and the results obtained were compared using voxelwise analysis. Areas of the brain that were significantly different were then examined using a region-of-interest analysis to compare these patients with healthy controls. Voxel-based morphometry was used to determine macroscopic differences in gray and white matter volume between patient groups. SETTING University-affiliated research institution. PARTICIPANTS A total of 20 drug-naive patients with PD (10 with tremor-dominant PD and 10 with nontremor-dominant PD) and a total of 20 healthy controls. MAIN OUTCOME MEASURES Blood oxygenation level-dependent activation and percent signal change. RESULTS Robust findings across both voxelwise and region-of-interest analyses showed that, compared with patients with tremor-dominant PD, patients with nontremor-dominant PD had reduced activation in the ipsilateral dorsolateral prefrontal cortex, the globus pallidus interna, and the globus pallidus externa. Region-of-interest analyses confirmed that patients with nontremor-dominant PD had reduced activity in the ipsilateral dorsolateral prefrontal cortex, the globus pallidus interna, and the globus pallidus externa compared with patients with tremor-dominant PD and healthy controls. Patients with tremor-dominant PD had increased activity in the contralateral dorsolateral prefrontal cortex compared with patients with nontremor-dominant PD and healthy controls. These results could not be explained by differences in gray or white matter volume. CONCLUSIONS Reduced brain activity occurs in the prefrontal cortex and globus pallidus of patients with nontremor-dominant PD compared with both patients with tremor-dominant PD and healthy controls

  7. 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

  8. Higher and lower active circulating VWF levels: different facets of von Willebrand disease.

    PubMed

    Casonato, Alessandra; Pontara, Elena; Morpurgo, Margherita; Sartorello, Francesca; De Groot, Philip G; Cattini, Maria G; Daidone, Viviana; De Marco, Luigi

    2015-12-01

    Most circulating von Willebrand factor (VWF) is normally inactive and incapable of binding platelets, but numerous disorders may modify the proportion of active VWF. We explored active VWF levels in patients with von Willebrand disease (VWD) whose VWF had a higher affinity for platelet glycoprotein (GP)Ib, but different susceptibilities to ADAMTS13 and multimer patterns (9 patients lacking large multimers, 10 with a normal pattern); 12 patients with VWF C2362F and R1819_C1948delinsS mutations, which make VWF resistant to ADAMTS13 were also studied. Type 2B patients with abnormal or normal multimers had significantly more active VWF (3·33 ± 1·6 and 3·74 ± 0·74, respectively; normal 0·99 ± 0·23). The type of VWF mutation influenced VWF activation: V1316M was associated with the highest levels in patients with abnormal multimers, and R1341W in those with normal multimers. Pregnancy induced gradually rising active VWF levels and declining platelet counts in one type 2B VWD patient without large multimers. Active VWF levels dropped significantly in patients homozygous for the C2362F mutation or heterozygous for R1819_C1948delinsS mutations (0·2 ± 0·03 and 0·23 ± 0·1, respectively), and less in cases heterozygous for the VWF C2362F mutation (0·55 ± 0·17). We demonstrate that VWF may be more or less activated, with or without any direct involvement of the A1 domain, and regardless of ADAMTS13.

  9. Physical activity in patients with stable coronary heart disease: an international perspective

    PubMed Central

    Stewart, Ralph; Held, Claes; Brown, Rebekkah; Vedin, Ola; Hagstrom, Emil; Lonn, Eva; Armstrong, Paul; Granger, Christopher B.; Hochman, Judith; Davies, Richard; Soffer, Joseph; Wallentin, Lars; White, Harvey

    2013-01-01

    Aims Despite the known benefits of regular exercise, the reasons why many coronary heart disease (CHD) patients engage in little physical activity are not well understood. This study identifies factors associated with low activity levels in individuals with chronic CHD participating in the STABILITY study, a global clinical outcomes trial evaluating the lipoprotein phospholipaseA2 inhibitor darapladib. Methods and results Prior to randomization, 15 486 (97.8%) participants from 39 countries completed a lifestyle questionnaire. Total physical activity was estimated from individual subject self-reports of hours spend each week on mild, moderate, and vigorous exercise, corresponding approximately to 2, 4, and 8 METS, respectively. Multivariate logistic regression evaluated clinical and demographic variables for the lowest compared with higher overall exercise levels, and for individuals who decreased rather than maintained or increased activity since diagnosis of CHD. The least active 5280 subjects (34%) reported exercise of ≤24MET.h/week. A total of 7191 subjects (46%) reported less exercise compared with before diagnosis of CHD. The majority of participants were either ‘not limited’ or ‘limited a little’ walking 100 m (84%), climbing one flight of stairs (82%), or walking 1 km/½ mile (68%), and <10% were limited ‘a lot’ by dyspnoea or angina. Variables independently associated with both low physical activity and decreasing exercise after diagnosis of CHD included more co-morbid conditions, poorer general health, fewer years of education, race, and country (P < 0.001 for all). Conclusion In this international study, low physical activity was only partly explained by cardiovascular symptoms. Potentially modifiable societal and health system factors are important determinants of physical inactivity in patients with chronic CHD. PMID:24014220

  10. Phospholipid transfer protein activity is associated with inflammatory markers in patients with cardiovascular disease.

    PubMed

    Cheung, Marian C; Brown, B Greg; Marino Larsen, Emily K; Frutkin, Andrew D; O'Brien, Kevin D; Albers, John J

    2006-01-01

    Plasma phospholipid lipid transfer protein (PLTP) has several known key functions in lipoprotein metabolism. Recent studies suggest that it also may play a role in the inflammatory response. Inflammatory cell activity contributes to the development of atherosclerosis. To seek further evidence for the association of PLTP with inflammation, we studied the relationship between PLTP activity and five inflammatory markers [C-reactive protein (CRP), serum amyloid A (SAA), interleukin 6 (IL-6), white blood cells (WBC), and fibrinogen] in 93 patients with low HDL and cardiovascular disease (CVD). Plasma PLTP activity had the strongest correlation with CRP (r=0.332, P<0.001) followed by SAA (r=0.239, P=0.021). PLTP, CRP, and SAA were significantly associated with body mass index (BMI), insulin or glucose, apolipoprotein (apo) B, and/or apo E level (r=0.264-0.393, P<0.01). PLTP, SAA, and IL-6 also were associated with the concentration of HDL particles without apo A-II [Lp(A-I)](r=0.373-0.472, P<0.005, n=56), but not particles with apo A-II. Smoking was associated with increased PLTP activity, CRP, and WBC, and hypertension with increased PLTP activity. In linear models, CRP remained significantly associated with PLTP after adjustment of CVD risk factors and insulin resistance. Also, much of the variability of plasma PLTP activity was explained by CRP, BMI, Lp(A-I), smoking, glucose, and blood pressure. These findings show for the first time that plasma PLTP activity is associated positively with CRP in CVD, a state of chronic inflammation.

  11. Activity against multidrug-resistant Mycobacterium tuberculosis in Mexican plants used to treat respiratory diseases.

    PubMed

    Jimenez-Arellanes, Adelina; Meckes, Mariana; Ramirez, Raquel; Torres, Javier; Luna-Herrera, Julieta

    2003-09-01

    The increase of multidrug-resistant Mycobacterium tuberculosis (MDR-TB) demands the search for alternative antimycobacterial drugs. The aim of this study was to evaluate plants used in Mexican traditional medicine to treat respiratory diseases for activity against MDR-TB. A group of 22 plants was screened for activity against Mycobacterium tuberculosis H37Rv and Mycobacterium avium at concentrations from 50 to 200 microg/mL. The antimycobacterial effect was determined by a microcolorimetric assay with Alamar blue dye. None of the aqueous extracts had antimycobacterial activity. Hexane extracts from Artemisia ludoviciana, Chamaedora tepejilote, Lantana hispida, Juniperus communis and Malva parviflora, and methanol extracts from Artemisia ludoviciana and Juniperus communis inhibited the growth of Mycobacterium tuberculosis. Mycobacterium avium was inhibited by Juniperus communis hexane extract and by Malva parviflora methanol extract. The active extracts were tested against monoresistant variants of Mycobacterium tuberculosis H37Rv (isoniazid, rifampin, streptomycin and ethambutol resistant) and the hexane extract of Lantana hispida showed the best activity. Lantana hispida hexane extract was also active against a group of MDR-TB clinical isolates. In contrast, it did not inhibit the growth of non-tuberculous mycobacteria. The hexane extract of Lantana hispida was fractionated by column chromatography and one of its fractions (FVI) inhibited the growth of all the MDR-TB clinical isolates at concentrations up to 25 microg/mL. This study supports the fact that selecting plants by ethnobotanical criteria enhances the probability of finding species with activity against mycobacteria, and our results point to Lantana hispida as an important source of potential compounds against MDR-TB.

  12. Immune defects in active mycobacterial diseases in patients with primary immunodeficiency diseases (PIDs).

    PubMed

    Lee, Wen-I; Huang, Jing-Long; Yeh, Kuo-Wei; Jaing, Tang-Her; Lin, Tzou-Yien; Huang, Yhu-Chering; Chiu, Cheng-Hsun

    2011-12-01

    Natural human immunity to the mycobacteria group, including Mycobacterium tuberculosis, Bacille Calmette-Guérin (BCG) or nontuberculous mycobacteria (NTM), and/or Salmonella species, relies on the functional IL-12/23-IFN-γ integrity of macrophages (monocyte/dendritic cell) connecting to T lymphocyte/NK cells. Patients with severe forms of primary immunodeficiency diseases (PIDs) have more profound immune defects involving this impaired circuit in patients with severe combined immunodeficiencies (SCID) including complete DiGeorge syndrome, X-linked hyper IgM syndrome (HIGM) (CD40L mutation), CD40 deficiency, immunodeficiency with or without anhidrotic ectodermal dysplasia (NEMO and IKBA mutations), chronic granulomatous disease (CGD) and hyper IgE recurrent infection syndromes (HIES). The patients with severe PIDs have broader diverse infections rather than mycobacterial infections. In contrast, patients with an isolated inborn error of the IL-12/23-IFN-γ pathway are exclusively prone to low-virulence mycobacterial infections and nontyphoid salmonella infections, known as Mendelian susceptibility to the mycobacterial disease (MSMD) phenotype. Restricted defective molecules in the circuit, including IFN-γR1, IFN-γR2, IL-12p40, IL-12R-β1, STAT-1, NEMO, IKBA and the recently discovered CYBB responsible for autophagocytic vacuole and proteolysis, and interferon regulatory factor 8 (IRF8) for dendritic cell immunodeficiency, have been identified in around 60% of patients with the MSMD phenotype. Among all of the patients with PIDs referred for investigation since 1985, we have identified four cases with the specific defect (IFNRG1 for three and IL12RB for one), presenting as both BCG-induced diseases and NTM infections, in addition to some patients with SCID, HIGM, CGD and HIES. Furthermore, manifestations in patients with autoantibodies to IFN-γ (autoAbs-IFN-γ), which is categorized as an anticytokine autoantibody syndrome, can resemble the relatively persistent

  13. Clinical assessment of disease activity in rheumatoid arthritis: evaluation of a functional test.

    PubMed Central

    Kalla, A A; Kotze, T J; Meyers, O L; Parkyn, N D

    1988-01-01

    A cross sectional analysis of the correlation between clinical, laboratory, and radiological markers of disease activity in 98 patients with classical rheumatoid arthritis (RA) is reported. The median age was 38 years, the median age at onset of disease 29 years, and the median duration of disease seven years. The Keitel function test (KFT) showed good correlation with the Ritchie articular index (RAI) (p less than 0.0001; r = 0.5) and the disability questionnaire (DQ) (p less than 0.0001; r = 0.6). The RAI and DQ correlated weakly with laboratory variables, while the KFT showed significant correlation with the erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and plasma viscosity (PV) (p less than 0.001; r = 0.4; 0.3; 0.4). Only the KFT showed significant correlations with bone mass measurements (p less than 0.01; r = -0.3; -0.4), and the Larsen index at the right wrist (p less than 0.0001; r = 0.4). Consensus analysis suggested that the KFT is a useful single clinical test of disease activity in RA. The hand functional index (HFI), a component of the KFT, showed significant correlation with the total KFT (r = 0.9). Prospective drug trials are needed to establish the value of the HFI in the monitoring of patients with RA. PMID:3263089

  14. Disease activity in Graves' ophthalmopathy: diagnosis with orbital MR imaging and correlation with clinical score.

    PubMed

    Tortora, Fabio; Cirillo, Mario; Ferrara, Marco; Belfiore, Maria Paola; Carella, Carlo; Caranci, Ferdinando; Cirillo, Sossio

    2013-10-01

    In Graves' ophthalmopathy (GO) it is important to distinguish acute inflammation at an early stage, responsive to immunosuppressive treatment, from inactive fibrotic end stage disease, unresponsive to the same treatment. The purpose of this study was to identify the most relevant signal intensities on orbital MR imaging with contrast administration both to classify patients according to their clinical activity score (defined by a cut-off value of 3) and to make a prediction of patient's CAS. Such threshold was considered as widely used in literature. Sixteen consecutive patients with a diagnosis of GO in different phases of thyroid disease based on clinical and orbital MR imaging signs, and six normal volunteers were examined. Orbital MR imaging was performed on a 1.5 Tesla MR Unit. MR scans were assessed by an experienced neuroradiologist, blinded to the clinical examinations. We found a statistical correlation between CAS and both STIR and contrast enhanced T1-weighted sequences. There was also a statistically significant correlation between STIR and contrast-enhanced T1 images disclosing the possibility of avoiding the injection of contrast medium. Our study proved that signal intensity values on STIR sequence increase in the inflammatory oedematous phase of disease. We confirmed the correlation between signal intensities on this sequence and CAS, showing an increase in signal intensity proportional to the CAS value. So we validated MRI use to establish the activity phase of disease more sensitively than CAS alone.

  15. Novel risk factors of cardiovascular disease and their associations between obesity, physical activity and physical fitness.

    PubMed

    Buchan, Duncan S; Thomas, Non E; Baker, Julien S

    2012-02-17

    The prevalence of cardiovascular disease (CVD) is increasing around the globe and is the leading cause of death around the world. Though once thought of as an adult problem, it is now recognised that the early manifestations of disease may occur during childhood. Numerous risk factors have been linked to CVD with much of the research focusing on understanding the prevalence and relationship of traditional risk factors such as dyslipidemia, smoking, diabetes mellitus, hypertension, obesity, psychosocial stress, poor diet, physical inactivity and alcohol consumption to the early etiology of disease. While this line of investigation has greatly enhanced our understanding of the relationship between these risk factors and disease, they do not fully explain all cardiovascular events. To enhance our understanding and help with the management of CVD, investigations that involve the measurement of traditional as well as novel risk factors may be necessary. Public health strategies that aim to reduce the prevalence of obesity and overweight encourage youth to increase their physical activity levels as a means of protecting against poor cardiometabolic profiles. Interventions that increase physical activity levels and improve cardiorespiratory fitness cause a reduction in certain CVD risk factors but the lack of agreement between findings makes it impossible to give precise recommendations that will ensure CVD risk reduction. Yet it is important that research continues in order to establish the most appropriate means of improving the health and well-being of those at most risk of future CVD.

  16. Profile of patients with chronic obstructive pulmonary disease classified as physically active and inactive according to different thresholds of physical activity in daily life

    PubMed Central

    Furlanetto, Karina C.; Pinto, Isabela F. S.; Sant’Anna, Thais; Hernandes, Nidia A.; Pitta, Fabio

    2016-01-01

    ABSTRACT Objective To compare the profiles of patients with chronic obstructive pulmonary disease (COPD) considered physically active or inactive according to different classifications of the level of physical activity in daily life (PADL). Method Pulmonary function, dyspnea, functional status, body composition, exercise capacity, respiratory and peripheral muscle strength, and presence of comorbidities were assessed in 104 patients with COPD. The level of PADL was quantified with a SenseWear Armband activity monitor. Three classifications were used to classify the patients as physically active or inactive: 30 minutes of activity/day with intensity >3.2 METs, if age ≥65 years, and >4 METs, if age <65 years; 30 minutes of activity/day with intensity >3.0 METs, regardless of patient age; and 80 minutes of activity/day with intensity >3.0 METs, regardless of patient age. Results In all classifications, when compared with the inactive group, the physically active group had better values of anthropometric variables (higher fat-free mass, lower body weight, body mass index and fat percentage), exercise capacity (6-minute walking distance), lung function (forced vital capacity) and functional status (personal care domain of the London Chest Activity of Daily Living). Furthermore, patients classified as physically active in two classifications also had better peripheral and expiratory muscle strength, airflow obstruction, functional status, and quality of life, as well as lower prevalence of heart disease and mortality risk. Conclusion In all classification methods, physically active patients with COPD have better exercise capacity, lung function, body composition, and functional status compared to physically inactive patients. PMID:27683835

  17. Transgenerational transmission of systemic mast cell activation disease-genetic and epigenetic features.

    PubMed

    Molderings, Gerhard J

    2016-08-01

    Systemic mast cell activation disease (MCAD) comprises disorders characterized by an enhanced release of mast cell mediators accompanied by a varying accumulation of dysfunctional mast cells. Within the last years, evidence has been presented that MCAD is a multifactorial polygenic determined disease with the KIT(D816V) mutation and its induced functional consequences considered as special case. The respective genes encode proteins for various signaling pathways, epigenetic regulators, the RNA splicing machinery, and transcription factors. Transgenerational transmission of MCAD appears to be quite common. The basics of the molecular mechanisms underlying predisposition of the disease, that is, somatic and germline mutations and the contribution of epigenetic processes have become identifiable. The aim of the present review is to present and discuss available genetic, epigenetic and epidemiological findings, and to present a model of MCAD pathogenesis.

  18. Environmental factors, immune changes and respiratory diseases in troops during military activities.

    PubMed

    Korzeniewski, Krzysztof; Nitsch-Osuch, Aneta; Chciałowski, Andrzej; Korsak, Jolanta

    2013-06-01

    Combat operations in contemporary theaters of war, as well as combat training, are carried out in all parts of the world, typically in a harsh environment. Specific environmental conditions, such as heat, cold, high-altitudes, desert climates, as well as chemical and biological pollution of both the atmosphere and soil, together with over-exertion, food restrictions, sleep deprivation, and psychological stress can all result in changes in the immune system and the occurrence of associated diseases. Respiratory diseases are one of the most common health problems among military personnel participating in combat training or deployed to operations in areas characterized by difficult climatic and sanitary conditions. They are, therefore, one of the main reasons for military personnel requiring ambulant and hospital treatment. The aim of the study was to discuss the influence of environmental factors and the conditions in which active duty is performed on changes in the immune system and the occurrence of respiratory tract diseases in a military environment.

  19. Hypersensitivity pneumonitis in nonhuman primates: studies on the relationship of immunoregulation and disease activity

    SciTech Connect

    Keller, R.H.; Calvanico, N.J.; Stevens, J.O.

    1982-01-01

    We investigated the relationship of immunoregulation to disease activity in a nonhuman primate model of pigeon breeder's disease. Two Macaca arctoides monkeys developed classical symptoms of hypersensitivity pneumonitis after sensitization and prolonged bronchial challenge, whereas 2 other monkeys remained asymptomatic after in vivo challenge. There were no differences in the percentages of T cells, B cells, monocytes, or FC..gamma..-bearing T cells between symptomatic and asymptomatic animals. Nonetheless, we found a population of concanavalin A-induced, pigeon serum- (PS) induced, and spontaneous T cells that functioned as suppressor cells in autologous in vitro co-cultures in asymptomatic animals that were missing or nonfunctional in symptomatic animals. Monocyte suppressors functioned in both groups. We used low-dose total body irradiation (TBI) to inactivate T suppressor cells. Fifteen radiation units of TBI caused no change in the physical activity, routine chemistries, or blood counts of the 4 animals. After TBI, however, the previously asymptomatic animals developed fever, tachypnea, and signs of pulmonary congestion after in vivo challenge with PS. There was no change in the response to challenge in the symptomatic group. This altered response to in vivo challenge in the previously asymptomatic group persisted for 2 wk after TBI. During this period the difference in in vitro immunoregulatory activity between Con A-induced, PS-induced, and spontaneous T cells in symptomatic and asymptomatic animals disappeared. Monocyte suppressors, however, continued to function in both groups after TBI. these data suggest that the monkey is an appropriate model for studies of human HP and that T cell immunoregulation may be an important element in the pathogenesis and disease activity of HP.

  20. Lack of Association between Selenium Status and Disease Severity and Activity in Patients with Graves' Ophthalmopathy

    PubMed Central

    Dehina, Nora; Hofmann, Peter Josef; Behrends, Thomas; Eckstein, Anja; Schomburg, Lutz

    2016-01-01

    Background Selenium (Se) is of importance for regular functioning of the immune system and thyroid gland, and may have a health effect in mild Graves' ophthalmopathy (GO). Objective As the Se status declines in inflammation, we analyzed whether GO activity or severity affects the Se status of patients. Methods Serum Se and selenoprotein P (SePP) concentrations were retrospectively determined in 84 consecutive GO patients before treatment and compared to their clinical activity score (CAS) and severity of eye changes (NOSPECS) status, and to the concentrations of autoantibodies targeting the TSH receptor (TRAK) or the IGF1 receptor (IGF1R-aAB). Results Serum Se and SePP were linearly associated, indicating a suboptimal Se status of our patients. In comparison to data from other European cohorts, the majority of GO patients had a relatively poor Se status ([Se] ± SD; 70.0 ± 23.8 µg/l), below the threshold needed for full expression of selenoproteins. TRAK were inversely associated with Se concentrations, while IGF1R-aAB titers were not associated with Se. Neither Se nor SePP concentrations differed between GO patients with severe versus mild or active versus inactive disease, or showed significant associations with the CAS or NOSPECS values. Conclusion GO patients are at risk of a low Se status, yet disease severity or activity does not seem to affect Se or SePP concentrations directly. However, as the retrospective nature of the analysis does not allow conclusions on a potential causative role of Se on Graves' disease or GO risk, these results neither support nor discourage adjuvant Se supplementation attempts. PMID:27099840

  1. Protein Kinase Activity Decreases with Higher Braak Stages of Alzheimer’s Disease Pathology

    PubMed Central

    Rosenberger, Andrea F.N.; Hilhorst, Riet; Coart, Elisabeth; García Barrado, Leandro; Naji, Faris; Rozemuller, Annemieke J.M.; van der Flier, Wiesje M.; Scheltens, Philip; Hoozemans, Jeroen J.M.; van der Vies, Saskia M.

    2015-01-01

    Alzheimer’s disease (AD) is characterized by a long pre-clinical phase (20–30 years), during which significant brain pathology manifests itself. Disease mechanisms associated with pathological hallmarks remain elusive. Most processes associated with AD pathogenesis, such as inflammation, synaptic dysfunction, and hyper-phosphorylation of tau are dependent on protein kinase activity. The objective of this study was to determine the involvement of protein kinases in AD pathogenesis. Protein kinase activity was determined in postmortem hippocampal brain tissue of 60 patients at various stages of AD and 40 non-demented controls (Braak stages 0-VI) using a peptide-based microarray platform. We observed an overall decrease of protein kinase activity that correlated with disease progression. The phosphorylation of 96.7% of the serine/threonine peptides and 37.5% of the tyrosine peptides on the microarray decreased significantly with increased Braak stage (p-value <0.01). Decreased activity was evident at pre-clinical stages of AD pathology (Braak I-II). Increased phosphorylation was not observed for any peptide. STRING analysis in combination with pathway analysis and identification of kinases responsible for peptide phosphorylation showed the interactions between well-known proteins in AD pathology, including the Ephrin-receptor A1 (EphA1), a risk gene for AD, and sarcoma tyrosine kinase (Src), which is involved in memory formation. Additionally, kinases that have not previously been associated with AD were identified, e.g., protein tyrosine kinase 6 (PTK6/BRK), feline sarcoma oncogene kinase (FES), and fyn-associated tyrosine kinase (FRK). The identified protein kinases are new biomarkers and potential drug targets for early (pre-clinical) intervention. PMID:26519433

  2. Gastric myoelectrical activity in patients with Parkinson's disease: evidence of a primary gastric abnormality.

    PubMed

    Soykan, I; Lin, Z; Bennett, J P; McCallum, R W

    1999-05-01

    Parkinson's disease patients may experience various gastrointestinal symptoms; however, the exact pathophysiology of these symptoms is not fully understood. Therefore, the aim of this study was to investigate the pattern of gastric myoelectrical activity in patients with Parkinson's disease. Eleven patients with Parkinson's disease and 10 healthy subjects participated in the study. Patients were stratified as "receiving dopaminergic therapy" (N = 5) and "off therapy" (N = 6). Gastric myoelectrical activity was measured by means of surface electrogastrography (EGG) for 30 min before and for 90 min after a standardized meal. The dominant frequency, postprandial EGG power change, and the percentage of normal 2-4 cycles/min (cpm) slow-wave activity in the three groups were calculated and compared. The mean postprandial EGG power increase in the untreated patients was smaller than in the treated patients (-3.11 +/- 1.01 and 1.17 +/- 1.96 dB; P = 0.072). Moreover, both of these values were significantly decreased when compared to the control group (untreated vs control: -3.11 +/- 1.01 vs 8.01 +/- 1.86 dB; P = 0.04 and treated vs control: 1.17 +/- 1.96 vs 8.01 +/- 1.86 dB; P = 0.02). The percentage of normal 2-4 cpm slow waves in untreated patients was not different from the treated patients (82.6 +/- 6.6% vs 75.8 +/- 13.6%, P = NS) or from the control group (88.2 +/- 5.4%, P = NS). The dominant frequency after the meal was similar to that in the fasting state both in the untreated (3.3 +/- 0.1 vs 3.2 +/- 0.2 cpm; P = NS) and treated patients (3.2 +/- 0.1 vs 3.1 +/- 0.1 cpm, P = NS), whereas the dominant frequency significantly increased postprandially in the control group (2.88 +/- 0.12 vs 3.05 +/- 0.16; P < 0.05). Abnormalities in gastric myoelectrical activity in untreated Parkinson's disease patients reflect direct involvement of the gastrointestinal tract by the primary disease process. EGG can be regarded as a useful diagnostic tool in evaluating gastrointestinal

  3. The Impact of Physical Activity on Non-Motor Symptoms in Parkinson's Disease: A Systematic Review.

    PubMed

    Cusso, Melanie E; Donald, Kenneth J; Khoo, Tien K

    2016-01-01

    Parkinson's disease (PD) is a neurological disorder that is associated with both motor and non-motor symptoms (NMS). The management of PD is primarily via pharmaceutical treatment; however, non-pharmaceutical interventions have become increasingly recognized in the management of motor and NMS. In this review, the efficacy of physical activity, including physiotherapy and occupational therapy, as an intervention in NMS will be assessed. The papers were extracted between the 20th and 22nd of June 2016 from PubMed, Web of Science, Medline, Ovid, SportsDiscuss, and Scopus using the MeSH search terms "Parkinson's," "Parkinson," and "Parkinsonism" in conjunction with "exercise," "physical activity," "physiotherapy," "occupational therapy," "physical therapy," "rehabilitation," "dance," and "martial arts." Twenty studies matched inclusion criteria of having 10 or more participants with diagnosed idiopathic PD participating in the intervention as well as having to evaluate the effects of physical activity on NMS in PD as controlled, randomized intervention studies. The outcomes of interest were NMS, including depression, cognition, fatigue, apathy, anxiety, and sleep. Risk of bias in the studies was evaluated using the Cochrane Collaboration's tool for assessing risk of bias. Comparability of the various intervention methods, however, was challenging due to demographic variability and methodological differences. Nevertheless, physical activity can positively impact the global NMS burden including depression, apathy, fatigue, day time sleepiness, sleep, and cognition, thus supporting its therapeutic potential in neurodegenerative conditions such as PD. It is recommended that further adequately powered studies are conducted to assess the therapeutic role of physical activity on both motor and non-motor aspects of PD. These studies should be optimally designed to assess non-motor elements of disease using instruments validated in PD.

  4. Antiviral activity of Paulownia tomentosa against enterovirus 71 of hand, foot, and mouth disease.

    PubMed

    Ji, Ping; Chen, Changmai; Hu, Yanan; Zhan, Zixuan; Pan, Wei; Li, Rongrong; Li, Erguang; Ge, Hui-Ming; Yang, Guang

    2015-01-01

    The bark, leaves, and flowers of Paulownia trees have been used in traditional Chinese medicine to treat infectious and inflammatory diseases. We investigated the antiviral effects of Paulownia tomentosa flowers, an herbal medicine used in some provinces of P. R. China for the treatment of skin rashes and blisters. Dried flowers of P. tomentosa were extracted with methanol and tested for antiviral activity against enterovirus 71 (EV71) and coxsackievirus A16 (CAV16), the predominant etiologic agents of hand, foot, and mouth disease in P. R. China. The extract inhibited EV71 infection, although no effect was detected against CAV16 infection. Bioactivity-guided fractionation was performed to identify apigenin as an active component of the flowers. The EC50 value for apigenin to block EV71 infection was 11.0 µM, with a selectivity index of approximately 9.3. Although it is a common dietary flavonoid, only apigenin, and not similar compounds like naringenin and quercetin, were active against EV71 infection. As an RNA virus, the genome of EV71 has an internal ribosome entry site that interacts with heterogeneous nuclear ribonucleoproteins (hnRNPs) and regulates viral translation. Cross-linking followed by immunoprecipitation and reverse transcription-polymerase chain reaction (RT-PCR) analysis showed that EV71 RNA was associated with hnRNPs A1 and A2. Apigenin treatment disrupted this association, indicating that apigenin suppressed EV71 replication through a novel mechanism by targeting the trans-acting factors. This study therefore validates the effects of Paulownia against EV71 infection. It also yielded mechanistic insights on apigenin as an active compound for the antiviral activity of P. tomentosa against EV71 infection.

  5. Activation of cyclic GMP-AMP synthase by self-DNA causes autoimmune diseases.

    PubMed

    Gao, Daxing; Li, Tuo; Li, Xiao-Dong; Chen, Xiang; Li, Quan-Zhen; Wight-Carter, Mary; Chen, Zhijian J

    2015-10-20

    TREX1 is an exonuclease that digests DNA in the cytoplasm. Loss-of-function mutations of TREX1 are linked to Aicardi-Goutieres Syndrome (AGS) and systemic lupus erythematosus (SLE) in humans. Trex1(-/-) mice exhibit autoimmune and inflammatory phenotypes that are associated with elevated expression of interferon (IFN)-induced genes (ISGs). Cyclic GMP-AMP (cGAMP) synthase (cGAS) is a cytosolic DNA sensor that activates the IFN pathway. Upon binding to DNA, cGAS is activated to catalyze the synthesis of cGAMP, which functions as a second messenger that binds and activates the adaptor protein STING to induce IFNs and other cytokines. Here we show that genetic ablation of cGas in Trex1(-/-) mice eliminated all detectable pathological and molecular phenotypes, including ISG induction, autoantibody production, aberrant T-cell activation, and lethality. Even deletion of just one allele of cGas largely rescued the phenotypes of Trex1(-/-) mice. Similarly, deletion of cGas in mice lacking DNaseII, a lysosomal enzyme that digests DNA, rescued the lethal autoimmune phenotypes of the DNaseII(-/-) mice. Through quantitative mass spectrometry, we found that cGAMP accumulated in mouse tissues deficient in Trex1 or DNaseII and that this accumulation was dependent on cGAS. These results demonstrate that cGAS activation causes the autoimmune diseases in Trex1(-/-) and DNaseII(-/-) mice and suggest that inhibition of cGAS may lead to prevention and treatment of some human autoimmune diseases caused by self-DNA.

  6. Flow cytometric approach to human polymorphonuclear leukocyte activation induced by gingival crevicular fluid in periodontal disease.

    PubMed

    Biselli, R; Ferlini, C; Di Murro, C; Paolantonio, M; Fattorossi, A

    1995-08-01

    In gingival pockets of patients with periodontal disease, polymorphonuclear leukocytes (PMN) are in contact with a peculiar exudate, the gingival crevicular fluid (GCF). Because of the pivotal role played by PMN in periodontal disease, we evaluated the ability of GCF in modulating normal human PMN. GCF was obtained from two gingival sites with severe periodontitis (SP) and two gingival sites with only mild periodontitis (MP) in 12 patients. Purified PMN were exposed to GCF from SP and MP sites and, as a control, to sterile culture medium. GCF activity was evaluated by monitoring the modulation of membrane molecules relevant to cell function. Compared to control medium, GCF from SP and MP sites was able to induce an activation status in PMN evidenced by an increased CD11b (62 +/- 9% and 28 +/- 7%, respectively) and f-Met-Leu-Phe (56 +/- 5% and 31 +/- 7%, respectively) receptor expression, with a concomitant reduction of CD62L expression (56 +/- 8% and 23 +/- 7%, respectively). Thus, reflecting the clinical status, GCF from SP sites was significantly more efficient in affecting PMN than GCF from MP sites. Cell size modifications, evaluated as an additional indicator of PMN activation, were consistent with membrane molecule modulation. The difference in PMN-activating capacity between SP and MP was abrogated by the successful completion of an appropriate periodontal therapy that dramatically improved clinical status. This is the first direct demonstration that GCF from periodontitis has the capacity to activate normal resting PMN and that this capacity reflects the magnitude of the inflammatory process that takes place in the gingiva.

  7. Mean platelet volume as an indicator of disease activity in juvenile SLE.

    PubMed

    Yavuz, Sevgi; Ece, Aydin

    2014-05-01

    The aim of the study was to assess mean platelet volume (MPV) in children with systemic lupus erythematosus (SLE) at the active and inactive stages. Twenty children with SLE and 30 age- and gender-matched controls were enrolled. Demographic data, SLE disease activity index (SLEDAI), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), MPV, complement 3 (C3), complement 4 (C4), urine protein (Up), and urine creatinine (Ucr) values upon reactivation and remission phases were recorded. MPV was statistically higher in patients than in controls and significantly increased in active phase compared to inactive phase (p = 0.001). A MPV level of 8.4 fL was determined as predictive cutoff value of activation of SLE (sensitivity 75 %, specificity 90 %). MPV was positively correlated with SLEDAI (p = 0.01, r = 0.55), ESR (p = 0.01, r = 0.45), CRP (p = 0.04, r = 0.24), and Up/Ucr (p = 0.01, r = 0.45) and negatively correlated with C3 (p = 0.02, r = -0.36), albumin (p = 0.01, r = -0.63), and Hb (p = 0.01, r = -0.48). There was not any significant association between MPV and the histological classification of lupus nephritis (p = 0.65). MPV might be used as an early indicator of reactivation in children with SLE. MPV seemed to be more accurate than ESR, CRP, and C3 for monitoring the disease activity in SLE.

  8. Studies of generalized elemental imbalances in neurological disease patients using INAA (instrumental neutron activation analysis)

    SciTech Connect

    Ehmann, W.D.; Vance, D.E.; Khare, S.S.; Kasarskis, E.J.; Markesbery, W.R.

    1988-01-01

    Evidence has been presented in the literature to implicate trace elements in the etiology of several age-related neurological diseases. Most of these studies are based on brain analyses. Using instrumental neutron activation analysis (INAA), we have observed trace element imbalances in brains of patients with Alzheimer's disease, amyotrophic lateral sclerosis (ALS), and Picks's disease. The most prevalent elemental imbalances found in the brain were for bromine, mercury, and the alkali metals. In this study the authors report INAA studies of trace elements in nonneural tissues from Alzheimer's disease and ALS patients. Samples from household relatives were collected for use as controls wherever possible. Hair samples were washed according to the International Atomic Energy Agency recommended procedure. Fingernail samples were scraped with a quartz knife prior to washing by the same procedure. For ALS patients, blood samples were also collected. These data indicate that elemental imbalances in Alzheimer's disease and ALS are not restricted to the brain. Many elements perturbed in the brain are also altered in the several nonneural tissues examined to date. The imbalances in different tissues, however, are not always in the same direction. The changes observed may represent causes, effects, or simply epiphenomena. Longitudinal studies of nonneural tissues and blood, as well as tissue microprobe analyses at the cellular and subcellular level, will be required in order to better assess the role of trace elements in the etiology of these diseases.

  9. Correlation of disease activity in proliferative glomerulonephritis with glomerular spleen tyrosine kinase expression.

    PubMed

    McAdoo, Stephen P; Bhangal, Gurjeet; Page, Theresa; Cook, H Terence; Pusey, Charles D; Tam, Frederick W K

    2015-07-01

    Spleen tyrosine kinase (SYK) is an important component of the intracellular signaling pathway for various immunoreceptors. Inhibition of SYK has shown promise in preclinical models of autoimmune and glomerular disease. However, the description of SYK expression in human renal tissue, which would be desirable ahead of clinical studies, is lacking. Here we conducted immunohistochemical analysis for total and phosphorylated SYK in biopsy specimens from >120 patients with a spectrum of renal pathologies, including thin basement membrane lesion, minimal change disease, membranous nephropathy, IgA nephropathy, lupus nephritis, ANCA-associated glomerulonephritis, antiglomerular basement membrane disease, and acute tubular necrosis. We found significant SYK expression in proliferative glomerulonephritis and that glomerular expression levels correlated with presenting serum creatinine and histological features of disease activity that predict outcome in IgA nephropathy, lupus nephritis, ANCA-associated glomerulonephritis, and antiglomerular basement membrane disease. SYK was phosphorylated within pathological lesions, such as areas of extracapillary and endocapillary proliferation, and appeared to localize to both infiltrating leucocytes and to resident renal cells within diseased glomeruli. Thus SYK is associated with the pathogenesis of proliferative glomerulonephritides, suggesting that these conditions may respond to SYK inhibitor treatment.

  10. Seasonal Drivers of Pneumococcal Disease Incidence: Impact of Bacterial Carriage and Viral Activity

    PubMed Central

    Weinberger, Daniel M.; Grant, Lindsay R.; Steiner, Claudia A.; Weatherholtz, Robert; Santosham, Mathuram; Viboud, Cécile; O'Brien, Katherine L.

    2014-01-01

    Background. Winter-seasonal epidemics of pneumococcal disease provide an opportunity to understand the drivers of incidence. We sought to determine whether seasonality of invasive pneumococcal disease is caused by increased nasopharyngeal transmission of the bacteria or increased susceptibility to invasive infections driven by cocirculating winter respiratory viruses. Methods. We analyzed pneumococcal carriage and invasive disease data collected from children <7 years old in the Navajo/White Mountain Apache populations between 1996 and 2012. Regression models were used to quantify seasonal variations in carriage prevalence, carriage density, and disease incidence. We also fit a multivariate model to determine the contribution of carriage prevalence and RSV activity to pneumococcal disease incidence while controlling for shared seasonal factors. Results. The seasonal patterns of invasive pneumococcal disease epidemics varied significantly by clinical presentation: bacteremic pneumococcal pneumonia incidence peaked in late winter, whereas invasive nonpneumonia pneumococcal incidence peaked in autumn. Pneumococcal carriage prevalence and density also varied seasonally, with peak prevalence occurring in late autumn. In a multivariate model, RSV activity was associated with significant increases in bacteremic pneumonia cases (attributable percentage, 15.5%; 95% confidence interval [CI], 1.8%–26.1%) but was not associated with invasive nonpneumonia infections (8.0%; 95% CI, −4.8% to 19.3%). In contrast, seasonal variations in carriage prevalence were associated with significant increases in invasive nonpneumonia infections (31.4%; 95% CI, 8.8%–51.4%) but not with bacteremic pneumonia. Conclusions.The seasonality of invasive pneumococcal pneumonia could be due to increased susceptibility to invasive infection triggered by viral pathogens, whereas seasonality of other invasive pneumococcal infections might be primarily driven by increased nasopharyngeal

  11. 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

  12. Alveolar hydatid disease. Review of the surgical experience in 42 cases of active disease among Alaskan Eskimos.

    PubMed Central

    Wilson, J F; Rausch, R L; Wilson, F R

    1995-01-01

    OBJECTIVE: The authors reviewed the pathophysiology and clinical management of endemic alveolar hydatid disease in Alaskan Eskimos, incorporating recent developments in diagnosis and treatment. SUMMARY BACKGROUND DATA: Alveolar hydatid disease is a highly lethal zoonotic infection caused by the larval stage of Echinococcus multilocularis. This cestode is restricted geographically to northern climates, where foxes and small rodents represent the natural hosts. Domestic dogs also may serve as definitive hosts, and thus, transmit the parasite to humans. Human infection is characterized by the development of a cancer-like hepatic mass, which may extend to adjacent structures or metastasize to distant sites. If the infection goes untreated, mortality reaches 80%. METHODS: The medical records of all patients with alveolar hydatid disease diagnosed or treated at the Alaska Native Medical Center between 1951 and 1993 were reviewed. Forty-two cases of active disease are presented. RESULTS: Nine patients underwent resection of hepatic lesions with intent to cure, and each had a favorable result. Average post-diagnosis survival of those patients was 22 years; six still are living and free of disease. Partial resections or drainage procedures were performed in ten patients. Chemotherapy was used to augment the surgical treatment of eight patients, and four received chemotherapy alone, resulting in improved outcomes compared with historic controls. Late complications included hepatic abscess, biliary obstruction, and portal venous hypertension. CONCLUSIONS: Whereas alveolar hydatid disease rarely is encountered in other areas of North America, the biologic potential for spread of the disease may be increasing because of illegal importation of infected foxes to the Eastern seaboard. Therefore, the surgical community should maintain an awareness of the diagnosis and management of this potentially devastating parasitic infection. Images Figure 2. Figure 3. PMID:7717785

  13. Shoulder muscle activity in Parkinson's disease during multijoint arm movements across a range of speeds.

    PubMed

    Farley, Becky G; Sherman, Scott; Koshland, Gail F

    2004-01-01

    Bradykinesia is one of the primary symptoms of Parkinson disease and leads to significant functional limitations for patients. Single joint movement studies, that have investigated the mechanism of bradykinesia, suggest that several features of muscle activity are disrupted, including modulation of burst amplitude and duration, and the number of bursts. It has been proposed that it is the blending of these different burst deficits that collectively defines bradykinesia. This study adds two new approaches to the study of bradykinesia. First, we examined the features of shoulder muscle activities during multijoint arm movement in bradykinetic and control subjects, such that previously reported single joint hypotheses could be tested for generalized arm movement. Second, we directly manipulated speed while keeping distance constant for a large range of speeds. In this manner, we could compare individual trials of muscle activity between controls and subjects with Parkinson's disease (PD) for movements matched for both speed and movement duration. Our results showed that while a multiple burst pattern of shoulder muscles was a common strategy for all subjects (young, elderly controls and PD), subjects with PD showed several burst abnormalities, including deficits in initial agonist burst amplitude and duration at both fast and slow speeds. Subjects with PD also (1) failed to produce a one-burst pattern at fast speeds and, instead, produced a predominance of multiple burst patterns and (2) showed a relationship between the number of burst deficits and the severity of disease. These results extend the findings of single joint studies to multi-joint and similarly indicate that a combination of burst modulation abnormalities correlate with bradykinesia and disease severity.

  14. Activation of asparaginyl endopeptidase leads to Tau hyperphosphorylation in Alzheimer disease.

    PubMed

    Basurto-Islas, Gustavo; Grundke-Iqbal, Inge; Tung, Yunn Chyn; Liu, Fei; Iqbal, Khalid

    2013-06-14

    Neurofibrillary pathology of abnormally hyperphosphorylated Tau is a key lesion of Alzheimer disease and other tauopathies, and its density in the brain directly correlates with dementia. The phosphorylation of Tau is regulated by protein phosphatase 2A, which in turn is regulated by inhibitor 2, I2(PP2A). In acidic conditions such as generated by brain ischemia and hypoxia, especially in association with hyperglycemia as in diabetes, I2(PP2A) is cleaved by asparaginyl endopeptidase at Asn-175 into the N-terminal fragment (I2NTF) and the C-terminal fragment (I2CTF). Both I2NTF and I2CTF are known to bind to the catalytic subunit of protein phosphatase 2A and inhibit its activity. Here we show that the level of activated asparaginyl endopeptidase is significantly increased, and this enzyme and I2(PP2A) translocate, respectively, from neuronal lysosomes and nucleus to the cytoplasm where they interact and are associated with hyperphosphorylated Tau in Alzheimer disease brain. Asparaginyl endopeptidase from Alzheimer disease brain could cleave GST-I2(PP2A), except when I2(PP2A) was mutated at the cleavage site Asn-175 to Gln. Finally, an induction of acidosis by treatment with kainic acid or pH 6.0 medium activated asparaginyl endopeptidase and consequently produced the cleavage of I2(PP2A), inhibition of protein phosphatase 2A, and hyperphosphorylation of Tau, and the knockdown of asparaginyl endopeptidase with siRNA abolished this pathway in SH-SY5Y cells. These findings suggest the involvement of brain acidosis in the etiopathogenesis of Alzheimer disease, and asparaginyl endopeptidase-I2(PP2A)-protein phosphatase 2A-Tau hyperphosphorylation pathway as a therapeutic target.

  15. Serum Vitamin D Level and Rheumatoid Arthritis Disease Activity: Review and Meta-Analysis

    PubMed Central

    Lin, Jin; Liu, Jian; Davies, Michael L.; Chen, Weiqian

    2016-01-01

    Background The evidence from epidemiological studies concerning the relationship between serum vitamin D concentrations and rheumatoid arthritis (RA) is inconsistent. This meta-analysis is aimed at determining the magnitude of the correlation between this common autoimmune disease and vitamin D, an important nutrient known to dampen adaptive immune responses. Methods Through multiple search strategies, relevant literature was identified and evaluated for quality before May 16 2015. Data extracted from eligible studies was synthesized to calculate pooled correlation coefficient (r), mean difference (MD) and odds ratio (OR). The Venice criteria were applied to assess the credibility of the evidence for each statistically significant association. Results A total of 24 reports involving 3489 patients were selected for analysis. RA patients had lower vitamin D levels than healthy controls (MD:-16.52 nmol/L, 95% confidence intervals [CI]:-18.85 to -14.19 nmol/L). There existed a negative relationship between serum 25-hydroxyvitamin D (25OHD) level and disease activity index, e.g. 25OHD vs. Disease Activity Score in 28 joints (DAS28): r = -0.13, 95% CI -0.16 to -0.09; 25OHD vs. C-reactive protein: r = -0.12, 95% CI -0.23 to -0.00. Additionally, latitude-stratified subgroup analysis yielded a relatively stronger negative correlation between 25OHD and DAS28 in low-latitude areas. This inverse relationship also appeared more significant in developing countries than in developed countries. No publication bias was detected. Conclusion RA patients had lower vitamin D values than healthy controls. There was a negative association between serum vitamin D and RA disease activity. However, more strictly controlled studies are needed to validate these findings. PMID:26751969

  16. The epidemiology and prevention of congenital cytomegalovirus infection and disease: activities of the Centers for Disease Control and Prevention Workgroup.

    PubMed

    Ross, Danielle S; Dollard, Sheila C; Victor, Marcia; Sumartojo, Esther; Cannon, Michael J

    2006-04-01

    Perhaps no single cause of birth defects and developmental disabilities in the United States currently provides greater opportunity for improved outcomes in more children than congenital cytomegalovirus (CMV). --Cannon and Davis. BMC Public Health 2005;5:70 Each year in the United States, thousands of children and their families are affected by congenital cytomegalovirus (CMV) infection. More children may be affected by congenital CMV than by other, better known childhood conditions, such as Down syndrome, fetal alcohol syndrome, and spina bifida. The Centers for Disease Control and Prevention (CDC) has formed a Workgroup on Congenital CMV, led by the National Center on Birth Defects and Developmental Disabilities and the National Center on Infectious Diseases. This report provides background on congenital CMV infection and describes the goals and activities of the workgroup for reducing the burden of sequelae of congenital CMV infection.

  17. Monitoring of disease biomarkers activity and immunophenotyping as important factors in SLE clinical management.

    PubMed

    Subasic, Djemo; Karamehic, Jasenko; Delic-Sarac, Marina; Kasumovic, Mersija; Mekic, Mevludin; Eminovic, Izet; Hasanagic, Nermina

    2012-01-01

    The highly specific biomarkers for monitoring of SLE disease activity are not yet defined up to date, due to existing of different clinical SLE phenotypes caused by individual genetic variation. Basically, numerous clinical complications follow SLE patients such as nephritis, atherosclerosis and cardial, CNS, gastrointestinal and ophthalmological complications, as well. Their monitoring in clinical SLE management can be evaluated by analysing of specific biochemical parameters and require permanent clinical observation. The presence of ANAs and anti-ds-DNAs are usual diagnostic SLE autoimmunity parameters, while SLE disease activity biomarkers are C3 and C4 level, anticardiolipin antibodies, anti-Sm/RNPs and, recently level of CD4 and CD8 lymphocytes. However, the number of TCR molecules on the T-cells surface at SLE patients is lower then in normal condition, and otherwise for these receptors CD molecules make specific connection. On the other hand, the T lymphocytes can be also, therapeutical targets at SLE patients, because of their clear direct involving in SLE pathogenesis. The SLE phenotypes are characterized by double CD negativity ( CD3 +/-, CD4-) caused by abnormal level of IL-2 and IL-17. T-lymphocytes have usually alpha-beta and gamma-delta TCR receptors, but for SLE patients is characteristic lower number gama-delta TCR molecules, detected in the peripheral blood specimens. Taking into account all of the facts, we investigated the level of specific usual SLE activity biomarkers (anti-ds-DNAs, C3, C4, anticardiolipin antibodies (beta-2-IgG, beta-2-IgM, ACA-G, ACA-M, CD4 and CD8 level) in serum specimens of SLE patients who underwent to the corresponding chemotherapy in combination with other biochemical and clinical parameters. Once again proved to be, that SLE biomarker monitoring, could be useful aproach for SLE activity disease and prediction organ damage, as well. In our investigation we used the following methods: immunofluorescence microscopy (IFA

  18. [Are active neurons a better defense against aging in Alzheimer's disease?].

    PubMed

    Lucassen, P J; van Someren, E J; Swaab, D F

    1998-08-01

    This article deals with the question whether metabolic activity of neurons interferes with their survival during brain aging and Alzheimer's disease (AD). This 'use it or lose it' concept assumes that active neurons have a better chance to survive these conditions. We have monitored activity changes in human hypothalamic nuclei, that show differential survival patterns in aging and AD. The size of the Golgi apparatus (GA) was measured in e.g. the nucleus basalis of Meynert (NBM), that is severely affected in AD, and in the vasopressin (AVP) containing neurons of the supraoptic nucleus (SON) that remain very stable and show no cell loss. In the affected NBM, a strong reduction in activity was found in AD, whereas in the stable SON, an increased activity was present in both conditions. These findings agree with the concept that activation is associated with pronounced stability in aging and AD. Another hypothalamic nucleus is the biological clock (SCN), which is very sensitive to light input. It loses about 35% of its AVP cells in old rats. In order to test the hypothesis that extra stimulation prevents degeneration, the SCN in old rats was activated by means of an increased light input. This could indeed prevent the age-related loss of AVP-neurons in the SCN in low light conditions. Increased light also restored the age-related decreased amplitude in the sleep-wake rhythm. Furthermore, in AD patients, increased amounts of environmental light improved day-night rhythms and reduced behavioural disturbances. These observations are in line with the 'use it or lose it' concept. Furthermore, oxidative damage to the DNA was studied as a) it may accumulate during neuronal aging, and b) activated cells repair their DNA more efficiently. Whereas biochemical measurements of 8OHDG levels were not different in aging or AD, in situ end labeling, that detects fragmented DNA histologically, showed many positive neurons and glial cells in the AD, but not control, hippocampus

  19. Regional NAD(P)H:quinone oxidoreductase activity in Alzheimer's disease.

    PubMed

    SantaCruz, Karen S; Yazlovitskaya, Eugenia; Collins, Julie; Johnson, Jeff; DeCarli, Charles

    2004-01-01

    Converging evidence supports the role of oxidative stress in the pathology of Alzheimer's disease (AD). This notion is further supported by recent findings of increased NAD(P)H:quinone oxidodreductase (NQO1) activity, a potent antioxidant system, in association with hippocampal AD pathology. If increased NQO1 activity is truly related to the AD process, however, we would expect to see regional co-localization of NQO1 activity with AD pathology throughout affected brain regions and the absence of NQO1 activity in regions unaffected by AD. We examined this hypothesis by measuring NQO1 enzymatic activity and NQO1 immunohistochemical staining in regions commonly affected by the AD process such as frontal cortex and compared this to regions generally unaffected by the AD process such as occipital cortex, cerebellum, and substantia nigra for a group of AD patients and controls. The ratio of frontal to cerebellar NQO1 enzymatic activity was significantly increased in patients with AD (2.07 +/- 1.90) versus controls (0.60 +/- 0.31; P < 0.03). Moreover, regional immunohistochemical staining revealed specific localization of NQO1 staining to astrocytes and neurites surrounding senile plaques. The extent of immunohistochemical staining also closely correlated with the extent of local AD pathology across the various brain regions examined. Neuronal NQO1 staining seen in frontal cortex of AD patients was absent in frontal cortex of controls, but was found to the same extent in neurons of the substantia nigra of both AD patients and controls. We conclude that NQO1 activity co-localizes closely with AD pathology supporting a presumed role as an antioxidant system upregulated in response to the oxidative stress of the AD process. The antioxidant role for NQO1 is further supported by finding increased neuronal NQO1 activity in substantia nigra neurons of both AD patients and controls as this neuronal population is known to be under constant oxidative stress. While requiring further

  20. Selective Degeneration of Entorhinal-CA1 Synapses in Alzheimer's Disease via Activation of DAPK1

    PubMed Central

    Shu, Shu; Zhu, Houze; Tang, Na; Chen, Wenting; Li, Xinyan; Li, Hao; Pei, Lei; Liu, Dan; Mu, Yangling; Tian, Qing

    2016-01-01

    Excitatory pyramidal neurons in the entorhinal cortical layer II region (ECIIPN) form functional excitatory synapses with CA1 parvalbumin inhibitory neurons (CA1PV) and undergo selective degeneration in the early stages of Alzheimer's disease (AD). Here, we show that death-associated protein kinase 1 (DAPK1) is selectively activated in ECIIPN of AD mice. Inhibition of DAPK1 by deleting a catalytic domain or a death domain of DAPK1 rescues the ECIIPN-CA1PV synaptic loss and improves spatial learning and memory in AD mice. This study demonstrates that activation of DAPK1 in ECIIPN contributes to a memory loss in AD and hence warrants a promising target for the treatment of AD. SIGNIFICANCE STATEMENT Our recent study reported that excitatory pyramidal neurons in the entorhinal cortical layer II region (ECIIPN) target to CA1 parvalbumin-type inhibitory neurons (CA1PV) at a direct pathway and are one of the most vulnerable brain cells that are selectively degenerated in the early stage of Alzheimer's disease (AD). Our present study shows that death-associated protein kinase 1 (DAPK1) is selectively activated in ECIIPN of AD mice. Inhibition of DAPK1 by deleting a catalytic domain or a death domain of DAPK1 rescues the ECIIPN-CA1PV synaptic loss and improves spatial learning and memory in the early stage of AD. These data not only demonstrate a crucial molecular event for synaptic degeneration but also provide a therapeutic target for the treatment of AD. PMID:27798139

  1. The Activity of Menkes Disease Protein ATP7A Is Essential for Redox Balance in Mitochondria*

    PubMed Central

    Bhattacharjee, Ashima; Yang, Haojun; Duffy, Megan; Robinson, Emily; Conrad-Antoville, Arianrhod; Lu, Ya-Wen; Capps, Tony; Braiterman, Lelita; Wolfgang, Michael; Murphy, Michael P.; Yi, Ling; Kaler, Stephen G.; Lutsenko, Svetlana; Ralle, Martina

    2016-01-01

    Copper-transporting ATPase ATP7A is essential for mammalian copper homeostasis. Loss of ATP7A activity is associated with fatal Menkes disease and various other pathologies. In cells, ATP7A inactivation disrupts copper transport from the cytosol into the secretory pathway. Using fibroblasts from Menkes disease patients and mouse 3T3-L1 cells with a CRISPR/Cas9-inactivated ATP7A, we demonstrate that ATP7A dysfunction is also damaging to mitochondrial redox balance. In these cells, copper accumulates in nuclei, cytosol, and mitochondria, causing distinct changes in their redox environment. Quantitative imaging of live cells using GRX1-roGFP2 and HyPer sensors reveals highest glutathione oxidation and elevation of H2O2 in mitochondria, whereas the redox environment of nuclei and the cytosol is much less affected. Decreasing the H2O2 levels in mitochondria with MitoQ does not prevent glutathione oxidation; i.e. elevated copper and not H2O2 is a primary cause of glutathione oxidation. Redox misbalance does not significantly affect mitochondrion morphology or the activity of respiratory complex IV but markedly increases cell sensitivity to even mild glutathione depletion, resulting in loss of cell viability. Thus, ATP7A activity protects mitochondria from excessive copper entry, which is deleterious to redox buffers. Mitochondrial redox misbalance could significantly contribute to pathologies associated with ATP7A inactivation in tissues with paradoxical accumulation of copper (i.e. renal epithelia). PMID:27226607

  2. [Prevention of cardiovascular diseases through sport and physical activity: A question of intensity?].

    PubMed

    Wernhart, S; Dinic, M; Pressler, A; Halle, M

    2015-05-01

    Coronary artery disease is the leading cause of death worldwide. A sedentary lifestyle accounts for 9% of premature mortality and creates a substantial health economic burden. Measurement of physical activity in daily practice refers to metabolic equivalent tasks and assessment of cardiopulmonary fitness to measurements of peak oxygen uptake during ergometry, which can be used to classify an individual's physical activity and maximum exercise capacity. Physical activity is a multifunctional intervention tool in prevention, which exerts its effects on multiple biochemical pathways, in contrast to conventional drug therapy. These changes reduce cardiovascular morbidity and mortality. Moderate physical exercise reduces blood pressure, improves insulin sensitivity and dyslipidemia, improves body composition and enhances weight reduction. Exercise of higher intensity seems to have superior effects compared to moderate intensity training; however, the training volume also seems to be important, as negative effects of long-term intensive training have been reported, e.g. atrial fibrillation or coronary sclerosis. Overall, exercise training has a major role in primary prevention of cardiovascular disease but seems to have a maximum threshold for benefit, which may be exceeded by some individuals.

  3. The Activity of Menkes Disease Protein ATP7A Is Essential for Redox Balance in Mitochondria

    SciTech Connect

    Bhattacharjee, Ashima; Yang, Haojun; Duffy, Megan; Robinson, Emily; Conrad-Antoville, Arianrhod; Lu, Ya-Wen; Capps, Tony; Braiterman, Lelita; Wolfgang, Michael; Murphy, Michael P.; Yi, Ling; Kaler, Stephen G.; Lutsenko, Svetlana; Ralle, Martina

    2016-05-16

    Copper-transporting ATPase ATP7A is essential for mammalian copper homeostasis. Loss of ATP7A activity is associated with fatal Menkes disease and various other pathologies. In cells, ATP7A inactivation disrupts copper transport from the cytosol into the secretory pathway. Using fibroblasts from Menkes disease patients and mouse 3T3-L1 cells with a CRISPR/Cas9-inactivated ATP7A, we demonstrate that ATP7A dysfunction is also damaging to mitochondrial redox balance. In these cells, copper accumulates in nuclei, cytosol, and mitochondria, causing distinct changes in their redox environment. Quantitative imaging of live cells using GRX1-roGFP2 and HyPer sensors reveals highest glutathione oxidation and elevation of H2O2 in mitochondria, whereas the redox environment of nuclei and the cytosol is much less affected. Decreasing the H2O2 levels in mitochondria with MitoQ does not prevent glutathione oxidation; i.e. elevated copper and not H2O2 is a primary cause of glutathione oxidation. Redox misbalance does not significantly affect mitochondrion morphology or the activity of respiratory complex IV but markedly increases cell sensitivity to even mild glutathione depletion, resulting in loss of cell viability. Thus, ATP7A activity protects mitochondria from excessive copper entry, which is deleterious to redox buffers. Mitochondrial redox misbalance could significantly contribute to pathologies associated with ATP7A inactivation in tissues with paradoxical accumulation of copper (i.e. renal epithelia).

  4. Foodborne Diseases Active Surveillance Network-2 Decades of Achievements, 1996-2015.

    PubMed

    Henao, Olga L; Jones, Timothy F; Vugia, Duc J; Griffin, Patricia M

    2015-09-01

    The Foodborne Diseases Active Surveillance Network (FoodNet) provides a foundation for food safety policy and illness prevention in the United States. FoodNet conducts active, population-based surveillance at 10 US sites for laboratory-confirmed infections of 9 bacterial and parasitic pathogens transmitted commonly through food and for hemolytic uremic syndrome. Through FoodNet, state and federal scientists collaborate to monitor trends in enteric illnesses, identify their sources, and implement special studies. FoodNet's major contributions include establishment of reliable, active population-based surveillance of enteric diseases; development and implementation of epidemiologic studies to determine risk and protective factors for sporadic enteric infections; population and laboratory surveys that describe the features of gastrointestinal illnesses, medical care-seeking behavior, frequency of eating various foods, and laboratory practices; and development of a surveillance and research platform that can be adapted to address emerging issues. The importance of FoodNet's ongoing contributions probably will grow as clinical, laboratory, and informatics technologies continue changing rapidly.

  5. Foodborne Diseases Active Surveillance Network—2 Decades of Achievements, 1996–2015

    PubMed Central

    Jones, Timothy F.; Vugia, Duc J.; Griffin, Patricia M.

    2015-01-01

    The Foodborne Diseases Active Surveillance Network (FoodNet) provides a foundation for food safety policy and illness prevention in the United States. FoodNet conducts active, population-based surveillance at 10 US sites for laboratory-confirmed infections of 9 bacterial and parasitic pathogens transmitted commonly through food and for hemolytic uremic syndrome. Through FoodNet, state and federal scientists collaborate to monitor trends in enteric illnesses, identify their sources, and implement special studies. FoodNet’s major contributions include establishment of reliable, active population-based surveillance of enteric diseases; development and implementation of epidemiologic studies to determine risk and protective factors for sporadic enteric infections; population and laboratory surveys that describe the features of gastrointestinal illnesses, medical care–seeking behavior, frequency of eating various foods, and laboratory practices; and development of a surveillance and research platform that can be adapted to address emerging issues. The importance of FoodNet’s ongoing contributions probably will grow as clinical, laboratory, and informatics technologies continue changing rapidly. PMID:26292181

  6. Mitochondrial ATP synthase activity is impaired by suppressed O-GlcNAcylation in Alzheimer's disease

    PubMed Central

    Cha, Moon-Yong; Cho, Hyun Jin; Kim, Chaeyoung; Jung, Yang Ouk; Kang, Min Jueng; Murray, Melissa E.; Hong, Hyun Seok; Choi, Young-Joo; Choi, Heesun; Kim, Dong Kyu; Choi, Hyunjung; Kim, Jisoo; Dickson, Dennis W.; Song, Hyun Kyu; Cho, Jin Won; Yi, Eugene C.; Kim, Jungsu; Jin, Seok Min; Mook-Jung, Inhee

    2015-01-01

    Glycosylation with O-linked β-N-acetylglucosamine (O-GlcNAc) is one of the protein glycosylations affecting various intracellular events. However, the role of O-GlcNAcylation in neurodegenerative diseases such as Alzheimer's disease (AD) is poorly understood. Mitochondrial adenosine 5′-triphosphate (ATP) synthase is a multiprotein complex that synthesizes ATP from ADP and Pi. Here, we found that ATP synthase subunit α (ATP5A) was O-GlcNAcylated at Thr432 and ATP5A O-GlcNAcylation was decreased in the brains of AD patients and transgenic mouse model, as well as Aβ-treated cells. Indeed, Aβ bound to ATP synthase directly and reduced the O-GlcNAcylation of ATP5A by inhibition of direct interaction between ATP5A and mitochondrial O-GlcNAc transferase, resulting in decreased ATP production and ATPase activity. Furthermore, treatment of O-GlcNAcase inhibitor rescued the Aβ-induced impairment in ATP production and ATPase activity. These results indicate that Aβ-mediated reduction of ATP synthase activity in AD pathology results from direct binding between Aβ and ATP synthase and inhibition of O-GlcNAcylation of Thr432 residue on ATP5A. PMID:26358770

  7. Activity Parameters of Subthalamic Nucleus Neurons Selectively Predict Motor Symptom Severity in Parkinson's Disease

    PubMed Central

    Gulberti, Alessandro; Zittel, Simone; Tudor Jones, Adam A.; Fickel, Ulrich; Münchau, Alexander; Köppen, Johannes A.; Gerloff, Christian; Westphal, Manfred; Buhmann, Carsten; Hamel, Wolfgang; Engel, Andreas K.

    2014-01-01

    Parkinson's disease (PD) is a heterogeneous disorder that leads to variable expression of several different motor symptoms. While changes in firing rate, pattern, and oscillation of basal ganglia neurons have been observed in PD patients and experimental animals, there is limited evidence linking them to specific motor symptoms. Here we examined this relationship using extracellular recordings of subthalamic nucleus neurons from 19 PD patients undergoing surgery for deep brain stimulation. For each patient, ≥10 single units and/or multi-units were recorded in the OFF medication state. We correlated the proportion of neurons displaying different activities with preoperative Unified Parkinson's Disease Rating Scale subscores (OFF medication). The mean spectral power at sub-beta frequencies and percentage of units oscillating at beta frequencies were positively correlated with the axial and limb rigidity scores, respectively. The percentage of units oscillating at gamma frequency was negatively correlated with the bradykinesia scores. The mean intraburst rate was positively correlated with both bradykinesia and axial scores, while the related ratio of interspike intervals below/above 10 ms was positively correlated with these symptoms and limb rigidity. None of the activity parameters correlated with tremor. The grand average of all the significantly correlated subthalamic nucleus activities accounted for >60% of the variance of the combined bradykinetic-rigid and axial scores. Our results demonstrate that the occurrence of alterations in the rate and pattern of basal ganglia neurons could partly underlie the variability in parkinsonian phenotype. PMID:24790198

  8. Activity parameters of subthalamic nucleus neurons selectively predict motor symptom severity in Parkinson's disease.

    PubMed

    Sharott, Andrew; Gulberti, Alessandro; Zittel, Simone; Tudor Jones, Adam A; Fickel, Ulrich; Münchau, Alexander; Köppen, Johannes A; Gerloff, Christian; Westphal, Manfred; Buhmann, Carsten; Hamel, Wolfgang; Engel, Andreas K; Moll, Christian K E

    2014-04-30

    Parkinson's disease (PD) is a heterogeneous disorder that leads to variable expression of several different motor symptoms. While changes in firing rate, pattern, and oscillation of basal ganglia neurons have been observed in PD patients and experimental animals, there is limited evidence linking them to specific motor symptoms. Here we examined this relationship using extracellular recordings of subthalamic nucleus neurons from 19 PD patients undergoing surgery for deep brain stimulation. For each patient, ≥ 10 single units and/or multi-units were recorded in the OFF medication state. We correlated the proportion of neurons displaying different activities with preoperative Unified Parkinson's Disease Rating Scale subscores (OFF medication). The mean spectral power at sub-beta frequencies and percentage of units oscillating at beta frequencies were positively correlated with the axial and limb rigidity scores, respectively. The percentage of units oscillating at gamma frequency was negatively correlated with the bradykinesia scores. The mean intraburst rate was positively correlated with both bradykinesia and axial scores, while the related ratio of interspike intervals below/above 10 ms was positively correlated with these symptoms and limb rigidity. None of the activity parameters correlated with tremor. The grand average of all the significantly correlated subthalamic nucleus activities accounted for >60% of the variance of the combined bradykinetic-rigid and axial scores. Our results demonstrate that the occurrence of alterations in the rate and pattern of basal ganglia neurons could partly underlie the variability in parkinsonian phenotype.

  9. 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

  10. MPTP/MPP+ suppresses activation of protein C in Parkinson's disease.

    PubMed

    Chen, Teng; Hou, Ruihua; Li, Chao; Wu, Chengyuan; Xu, Shujun

    2015-01-01

    Endothelial dysfunction and disruption of the blood-brain barrier have been found to be associated with Parkinson's disease (PD). However, the mechanisms underlying these effects have yet to be elucidated. It has also been found that activated protein C (APC) displays neuroprotective properties. Presently, the effects of APC on PD remain unknown. Using a 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) neurotoxin rodent model of PD, we found that administration of MPTP can reduce expression of endothelial protein C receptor (EPCR), an N-glycosylated type I membrane protein that has the ability to enhance protein C activation. However, the use of MPTP does not alter levels of thrombomodulin. These findings were verified in an in vitro study showing that 1-methyl-4-phenylpyridinium (MPP+) treatment leads to suppression of EPCR along with reduction of protein C activation in human primary endothelial cells. Importantly, our results display that activation of the transcriptional factor SP1 is involved in the inhibitory effects of MPTP/MPP+ on EPCR expression. We found that using 300 nM of the SP1 inhibitor MIT can abolish the effects of MPP+ on EPCR expression. Consistently, SP1 silencing using small RNA interference was able to prevent the inhibitory effects of MPTP/MPP+ on the reduction of EPCR expression and impairment of protein C activation. Importantly, our results indicate that overexpression of SP1 inhibits EPCR promoter activity. Our study suggests that EPCR-APC may be a potential therapeutic target for endothelial dysfunction in PD.

  11. HbS Binding to GP1bα Activates Platelets in Sickle Cell Disease

    PubMed Central

    Gupta, Avinash; Chawla, Sheetal; Batra, Harish; Seth, Tulika

    2016-01-01

    Intravascular hemolysis increases the risk of thrombosis in hemolytic disorders. Our previous study showed that the binding of adult hemoglobin (HbA) to glycoprotein (GP) 1bα induced the activation of platelets. The elevated plasma Hb or platelet surface bound Hb positively correlated with platelet activation in patients with paroxysmal nocturnal hemoglobinuria (PNH). Furthermore, this study shows that the sickle Hb [HbS, occurs due to single nucleotide polymorphism at A>T of β-globin gene of Hb and causes sickle cell disease (SCD)] also bound to GP1bα and activated platelets in a concentration-dependent manner. The HbS bound to glycocalicin (extramembranous part of GP1bα) with KD ~ 10.46 ± 3 μM. HbS induced phosphorylation of signaling adapter proteins, such as Lyn, PI3K, Akt and ERK in platelets, and also increased the surface expression of platelet activation markers such as P-selectin (10.7 fold) and PAC1 binding (10.4 fold) in platelet surface in a concentration-dependent manner. HbS also increased the platelet microparticle-generation (4.7 fold) and thrombus-formation (4.3 fold) in a concentration-dependent manner. An elevated level of extracellular Hb in plasma correlated directly with platelet activation markers such as P-selectin (r = 0.7947), PAC1 binding (r = 0.5914) on platelet surface and plasma levels of platelet-derived microparticles (r = 0.7834) in patients with SCD. Our study therefore suggests that the HbS-induced platelet activation may play a crucial role in intravascular clot formation observed in SCD patients characterized by high propensity to vascular occlusion and hypercoagulable states. PMID:27936141

  12. Reduced Lysosomal Acid Lipase Activity in Adult Patients With Non-alcoholic Fatty Liver Disease

    PubMed Central

    Baratta, Francesco; Pastori, Daniele; Del Ben, Maria; Polimeni, Licia; Labbadia, Giancarlo; Di Santo, Serena; Piemonte, Fiorella; Tozzi, Giulia; Violi, Francesco; Angelico, Francesco

    2015-01-01

    Non-alcoholic fatty liver disease (NAFLD) is characterized by intra-hepatic fat accumulation and mechanisms involved in its pathogenesis are not fully explained. Lysosomal Acid Lipase (LAL) is a key enzyme in lipid metabolism. We investigated its activity in patients with fatty liver. LAL activity (nmol/spot/h) was measured in 100 adult healthy subjects (HS) and in 240 NAFLD patients. A sub-analysis on 35 patients with biopsy-proven non-alcoholic steatohepatitis (NASH) was performed. Median LAL activity was 1.15 (0.95–1.72) in HS. It was significantly reduced in NAFLD [0.78 (0.61–1.01), p < 0.001 vs. HS]. A further reduction was observed in the subgroup of NASH [0.67 (0.51–0.77), p < 0.001 vs. HS]. Patients with LAL activity below median had higher values of serum total cholesterol (p < 0.05) and LDL-c (p < 0.05), and increased serum liver enzymes (ALT, p < 0.001; AST, p < 0.01; GGT, p < 0.01). At multivariable logistic regression analysis, factors associated with LAL activity below median were ALT (OR: 1.018, 95% CI 1.004–1.032, p = 0.011) and metabolic syndrome (OR: 2.551, 95% CI 1.241–5.245, p = 0.011), whilst statin use predicted a better LAL function (OR: 0.464, 95% CI 0.248–0.866, p = 0.016). Our findings suggest a strong association between impaired LAL activity and NAFLD. A better knowledge of the role of LAL may provide new insights in NAFLD pathogenesis. PMID:26288848

  13. Reduced Lysosomal Acid Lipase Activity in Adult Patients With Non-alcoholic Fatty Liver Disease.

    PubMed

    Baratta, Francesco; Pastori, Daniele; Del Ben, Maria; Polimeni, Licia; Labbadia, Giancarlo; Di Santo, Serena; Piemonte, Fiorella; Tozzi, Giulia; Violi, Francesco; Angelico, Francesco

    2015-07-01

    Non-alcoholic fatty liver disease (NAFLD) is characterized by intra-hepatic fat accumulation and mechanisms involved in its pathogenesis are not fully explained. Lysosomal Acid Lipase (LAL) is a key enzyme in lipid metabolism. We investigated its activity in patients with fatty liver. LAL activity (nmol/spot/h) was measured in 100 adult healthy subjects (HS) and in 240 NAFLD patients. A sub-analysis on 35 patients with biopsy-proven non-alcoholic steatohepatitis (NASH) was performed. Median LAL activity was 1.15 (0.95-1.72) in HS. It was significantly reduced in NAFLD [0.78 (0.61-1.01), p < 0.001 vs. HS]. A further reduction was observed in the subgroup of NASH [0.67 (0.51-0.77), p < 0.001 vs. HS]. Patients with LAL activity below median had higher values of serum total cholesterol (p < 0.05) and LDL-c (p < 0.05), and increased serum liver enzymes (ALT, p < 0.001; AST, p < 0.01; GGT, p < 0.01). At multivariable logistic regression analysis, factors associated with LAL activity below median were ALT (OR: 1.018, 95% CI 1.004-1.032, p = 0.011) and metabolic syndrome (OR: 2.551, 95% CI 1.241-5.245, p = 0.011), whilst statin use predicted a better LAL function (OR: 0.464, 95% CI 0.248-0.866, p = 0.016). Our findings suggest a strong association between impaired LAL activity and NAFLD. A better knowledge of the role of LAL may provide new insights in NAFLD pathogenesis.

  14. Sexual activity and concerns in people with coronary heart disease from a population-based study

    PubMed Central

    Steptoe, Andrew; Jackson, Sarah E; Wardle, Jane

    2016-01-01

    Objective Sexual activity is a central component of intimate relationships, but sexual function may be impaired by coronary heart disease (CHD). There have been few representative population-based comparisons of sexual behaviour and concerns in people with and without CHD. We therefore investigated these issues in a large nationally representative sample of older people. Methods We analysed cross-sectional data from 2979 men and 3711 women aged 50 and older from the English Longitudinal Study of Ageing. Sexual behaviour and concerns were assessed by validated self-completion questionnaire and analyses were weighted for non-response. Covariates included age, partnerships status and comorbidities. Results There were 376 men and 279 women with CHD. Men with CHD were less likely to be sexually active (68.7% vs 80.0%, adjusted OR 0.62, 95% CI 0.47 to 0.81), thought less about sex (74.7% vs 81.9%, OR 0.72, CI 0.54 to 0.95), and reported more erectile difficulties (47.4% vs 38.1%, OR 1.46, CI 1.10 to 1.93) than men without CHD. Effects were more pronounced among those diagnosed within the past 4 years. Women diagnosed <4 years ago were also less likely to be sexually active (35.4% vs 55.6%, OR 0.44, CI 0.23 to 0.84). There were few differences in concerns about sexual activity. Cardiovascular medication showed weak associations with erectile dysfunction. Conclusions There is an association between CHD and sexual activity, particularly among men, but the impact of CHD is limited. More effective advice after diagnosis might reverse the reduction in sexual activity, leading to improved quality of life. PMID:27126394

  15. Appearance of monoclonal plasma cell diseases in whole-body magnetic resonance imaging and correlation with parameters of disease activity.

    PubMed

    Kloth, Jost K; Hillengass, Jens; Listl, Karin; Kilk, Kerstin; Hielscher, Thomas; Landgren, Ola; Delorme, Stefan; Goldschmidt, Hartmut; Kauczor, Hans-Ulrich; Weber, Marc-André

    2014-11-15

    The aim of our study was to assess in which way different infiltration patterns of monoclonal plasma cell diseases in whole-body (wb) magnetic resonance imaging (MRI) are associated with clinical stages, plasma cell content in bone marrow samples and established serum markers of disease activity. Institutional review board approval was obtained. We performed wb-MRI in 547 consecutive, unselected and untreated patients with monoclonal gammopathy of undetermined significance (MGUS, n=138), smoldering myeloma (SMM, n=157) and multiple myeloma (MM, n=252) on two 1.5 T MRI-scanners with body array coils. The studies were evaluated in consensus by two experienced radiologists blinded to the diagnosis. We observed focal lesions in 23.9% (MGUS), 34.4% (SMM) and 81.3% (MM), respectively. A diffuse infiltration pattern was detected in 38.4%, 45.9% and 71%, respectively. The differences between all infiltration patterns were significant (p<0.0001). The presence of focal lesions and the presence of a diffuse bone marrow infiltration was associated with an increased plasma cell percentage in bone marrow samples (median 22% vs. 14%, 26% vs. 10%, both p<0.0001) and monoclonal protein concentration (median 18 g/dl vs. 13 g/dl, p=0.003, 20 g/dl vs. 11 g/dl, p<0.0001). Further categorization of the diffuse infiltration patterns in wb-MRI into "salt-and-pepper," moderate and severe identified significant associations with M-protein (median g/dl for S+P/moderate/severe 23/18/25, p=0.04), plasma cell percentage in the bone marrow (median 25%/24%/40%, p=0.02), and age (median years 67/60/57, p<0.0001). Bone marrow infiltration in wb-MRI is significantly different between the various stages of plasma cell disease and correlates well with established markers of disease activity.

  16. Beta-glucuronidase and Beta-glucosidase activity in stool specimens of children with inflammatory bowel disease.

    PubMed

    Mroczyńska, Marta; Galecka, Miroslawa; Szachta, Patrycja; Kamoda, Dorota; Libudzisz, Zdzislawa; Roszak, Dorota

    2013-01-01

    The aim of the study was to analyze the differences in the activity of beta-glucuronidase and beta-glucosidase in stool specimens of children with Inflammatory Bowel Diseases (IBD) and healthy subjects. The disease activity was determined according to the PCDAI scale (Crohn disease) and Truelove-Witts scale (Ulcerative colitis). Enzyme activity was determined by spectrophotometry. There was a correlation between the level of beta - glucosidase activity in stool and patient's age in the group of healthy controls, but not in the IBD group. beta-glucosidase activity in IBD and healthy subjects stool specimens did not differ significantly. The activity of beta-glucuronidase in children with IBD was two times lower than in the healthy group and was correlated with age in children with IBD, but not in the group of healthy ones.

  17. Vitamin D and vitamin D receptor activators in treatment of hypertension and cardiovascular disease.

    PubMed

    Franczyk, Agata; Stolarz-Skrzypek, Katarzyna; Wesołowska, Anna; Czarnecka, Danuta

    2014-01-01

    Vitamin D plays an essential role in calcium homeostasis and bone metabolism, but recent research has exposed a larger spectrum of biological actions that also includes induction of cell proliferation, immunomodulation, and control of other hormonal systems. Many cells that play an important role in the cardiovascular system express the Vitamin D receptor (VDR) and respond to 1,25-(OH)2D (the active product of vitamin D conversion by hydroxylase) with cell-specific function and gene regulation. These cells include cardiomyocytes, vascular endothelial cells, vascular smooth muscle cells, phagocytes, and cells of the nephron, which produce renin. VDR activators (calcitriol and paricalcitol) are available for the treatment of vitamin D deficiency, which can result from inadequate cutaneous production and/or low dietary intake. Vitamin-D deficient patients present a higher risk of cardiovascular disease than the general population. Recent clinical observations have shown that VDR activator therapy provides survival benefit and also has a positive impact on cardiovascular function. Compelling results have arisen from previous studies of mice with disrupted genes of the vitamin D signaling pathways. In mice lacking VDR or CYP27B1 (1α-hydroxylase - an enzyme, which converts vitamin D to its active form), in addition to the expected phenotype (hypocalcaemia, secondary hyperparathyroidism and osteomalacia), development of hypertension and cardiac hypertrophy were also observed. Moreover, these mice presented with overexpression of renin and atrial natriuretic peptide. VDR may play a role in regulating smooth-muscle-cell (SMC) proliferation, thrombosis, fibrinolysis and vessel relaxation. The influence of VDR activators on the modulation of renin expression and vascular function may reduce mortality, organ damage, and cardiovascular morbidity in VDR-activator-treated patients with hypertension. Since clinical use of calcitriol is largely limited, because of the side effect

  18. The increased risk of active tuberculosis disease in patients with dermatomyositis – a nationwide retrospective cohort study

    PubMed Central

    Wu, Ping-Hsun; Lin, Yi-Ting; Yang, Yi-Hsin; Lin, Yu-Chih; Lin, Yi-Ching

    2015-01-01

    The risk of active tuberculosis (TB) in patients with dermatomyositis (DM) is poorly understood. The cohort study aimed to investigate the association between DM and the risk of active TB disease. We conducted a population based study on 4,958 patients with newly diagnosed DM and 19,832 matched controls according to age, sex, and index date between 1998 and 2008. The hazard ratios (HRs) and cumulative incidences of active TB disease between DM patients and controls were analyzed. During the study period, a total of 85 (1.7%) DM patients developed active TB disease, which was significantly higher than that of non-DM patients (0.64%). The incidence rate of active TB disease was higher among DM patients than controls (incidence rate ratio 2.95; 95% confidence interval [CI], 2.24 to 3.88). The Cox regression model demonstrated significantly higher active TB disease rate among DM patients compared with controls (adjusted HR, 2.64; 95% CI, 1.97 to 3.54; p < 0.001) after adjusting for age, sex, and underlying medical disorders. The most significant risk factors for developing active TB included male sex, diabetes mellitus comorbidity, and use of corticosteroids and azathioprine in DM patients. In conclusion, DM patients are at a greater risk for active TB disease. PMID:26573418

  19. The relationship between coenzyme Q10, oxidative stress, and antioxidant enzymes activities and coronary artery disease.

    PubMed

    Lee, Bor-Jen; Lin, Yi-Chin; Huang, Yi-Chia; Ko, Ya-Wen; Hsia, Simon; Lin, Ping-Ting

    2012-01-01

    A higher oxidative stress may contribute to the pathogenesis of coronary artery disease (CAD). The purpose of this study was to investigate the relationship between coenzyme Q10 concentration and lipid peroxidation, antioxidant enzymes activities and the risk of CAD. Patients who were identified by cardiac catheterization as having at least 50% stenosis of one major coronary artery were assigned to the case group (n = 51). The control group (n = 102) comprised healthy individuals with normal blood biochemical values. The plasma coenzyme Q10, malondialdehyde (MDA) and antioxidant enzymes activities (catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx)) were measured. Subjects with CAD had significant lower plasma coenzyme Q10, CAT and GPx activities and higher MDA and SOD levels compared to those of the control group. The plasma coenzyme Q10 was positively correlated with CAT and GPx activities and negatively correlated with MDA and SOD. However, the correlations were not significant after adjusting for the potential confounders of CAD with the exception of SOD. A higher level of plasma coenzyme Q10 (≥ 0.52 μmol/L) was significantly associated with reducing the risk of CAD. Our results support the potential cardioprotective impact of coenzyme Q10.

  20. Contribution of HN protein length diversity to Newcastle disease virus virulence, replication and biological activities

    PubMed Central

    Jin, Jihui; Zhao, Jing; Ren, Yingchao; Zhong, Qi; Zhang, Guozhong

    2016-01-01

    To evaluate the contribution of length diversity in the hemagglutinin-neuraminidase (HN) protein to the pathogenicity, replication and biological characteristics of Newcastle disease virus (NDV), we used reverse genetics to generate a series of recombinant NDVs containing truncated or extended HN proteins based on an infectious clone of genotype VII NDV (SG10 strain). The mean death times and intracerebral pathogenicity indices of these viruses showed that the different length mutations in the HN protein did not alter the virulence of NDV. In vitro studies of recombinant NDVs containing truncated or extended HN proteins revealed that the extension of HN protein increased its hemagglutination titer, receptor-binding ability and impaired its neuraminidase activity, fusogenic activity and replication ability. Furthermore, the hemadsorption, neuraminidase and fusogenic promotion activities at the protein level were consistent with those of viral level. Taken together, our results demonstrate that the HN biological activities affected by the C-terminal extension are associated with NDV replication but not the virulence. PMID:27833149

  1. Hydrogel scaffolds as in vitro models to study fibroblast activation in wound healing and disease

    PubMed Central

    Smithmyer, Megan E.; Sawicki, Lisa A.

    2014-01-01

    Wound healing results from complex signaling between cells and their environment in response to injury. Fibroblasts residing within the extracellular matrix (ECM) of various connective tissues are critical for matrix synthesis and repair. Upon injury or chronic insult, these cells activate into wound-healing cells, called myofibroblasts, and repair the damaged tissue through enzyme and protein secretion. However, misregulation and persistence of myofibroblasts can lead to uncontrolled accumulation of matrix proteins, tissue stiffening, and ultimately disease. Extracellular cues are important regulators of fibroblast activation and have been implicated in their persistence. Hydrogel-based culture models have emerged as useful tools to examine fibroblast response to ECM cues presented during these complex processes. In this Mini-Review, we will provide an overview of these model systems, which are built upon naturally-derived or synthetic materials, and mimic relevant biophysical and biochemical properties of the native ECM with different levels of control. Additionally, we will discuss the application of these hydrogel-based systems for the examination of fibroblast function and fate, including adhesion, migration, and activation, as well as approaches for mimicking both static and temporal aspects of extracellular environments. Specifically, we will highlight hydrogels that have been used to investigate the effects of matrix rigidity, protein binding, and cytokine signaling on fibroblast activation. Last, we will describe future directions for the design of hydrogels to develop improved synthetic models that mimic the complex extracellular environment. PMID:25379176

  2. Lithium activates brain phospholipase A2 and improves memory in rats: implications for Alzheimer's disease.

    PubMed

    Mury, Fábio B; da Silva, Weber C; Barbosa, Nádia R; Mendes, Camila T; Bonini, Juliana S; Sarkis, Jorge Eduardo Souza; Cammarota, Martin; Izquierdo, Ivan; Gattaz, Wagner F; Dias-Neto, Emmanuel

    2016-10-01

    Phospholipase A2 (Pla2) is required for memory retrieval, and its inhibition in the hippocampus has been reported to impair memory acquisition in rats. Moreover, cognitive decline and memory deficits showed to be reduced in animal models after lithium treatment, prompting us to evaluate possible links between Pla2, lithium and memory. Here, we evaluated the possible modulation of Pla2 activity by a long-term treatment of rats with low doses of lithium and its impact in memory. Wistar rats were trained for the inhibitory avoidance task, treated with lithium for 100 days and tested for perdurability of long-term memory. Hippocampal samples were used for quantifying the expression of 19 brain-expressed Pla2 genes and for evaluating the enzymatic activity of Pla2 using group-specific radio-enzymatic assays. Our data pointed to a significant perdurability of long-term memory, which correlated with increased transcriptional and enzymatic activities of certain members of the Pla2 family (iPla2 and sPla2) after the chronic lithium treatment. Our data suggest new possible targets of lithium, add more information on its pharmacological activity and reinforce the possible use of low doses of lithium for the treatment of neurodegenerative conditions such as the Alzheimer's disease.

  3. Daily energy expenditure, physical activity, and weight loss in Parkinson's disease patients.

    PubMed

    Delikanaki-Skaribas, Evangelia; Trail, Marilyn; Wong, William Wai-Lun; Lai, Eugene C

    2009-04-15

    Patients with Parkinson's disease (PD) commonly exhibit weight loss (WL) which investigators attribute to various factors, including elevated energy expenditure. We tested the hypothesis that daily energy expenditure (DEE) and its components, resting energy expenditure (REE) and physical activity (PA) energy expenditure (PAEE), are elevated in WL compared with weight stable (WS) PD patients. We measured DEE in 10 PD WL patients and 10 PD WS patients using doubly labeled water (DLW). PAEE was estimated with DLW, activity monitors, and activity questionnaires. REE was measured with indirect calorimetry. We evaluated energy intake (EI) with a patient's 3-day food diary. Data was assessed employing SPSS, Spearman correlation coefficients, and Bland and Altman plots. There was no difference in DEE between the WL and WS groups measured with DLW. There were no differences in REE and EI between groups. DEE (r = 0.548, P < 0.05) and PAEE (r = 0.563, P < 0.01) are related with caloric intake. The WL group had higher PA than the WS group (P < 0.042) only when measured with wrist activity monitors. Results suggest that WL in PD patients cannot be fully explained by an increase in DEE. Large longitudinal studies to examine multiple relationships between variables might provide us with a better understanding of WL among PD patients.

  4. Rhes, a striatal-selective protein implicated in Huntington disease, binds beclin-1 and activates autophagy.

    PubMed

    Mealer, Robert G; Murray, Alexandra J; Shahani, Neelam; Subramaniam, Srinivasa; Snyder, Solomon H

    2014-02-07

    The protein mutated in Huntington disease (HD), mutant huntingtin (mHtt), is expressed throughout the brain and body. However, the pathology of HD is characterized by early and dramatic destruction selectively of the striatum. We previously reported that the striatal-specific protein Rhes binds mHtt and enhances its cytotoxicity. Moreover, Rhes-deleted mice are dramatically protected from neurodegeneration and motor dysfunction in mouse models of HD. We now report a function of Rhes in autophagy, a lysosomal degradation pathway implicated in aging and HD neurodegeneration. In PC12 cells, deletion of endogenous Rhes decreases autophagy, whereas Rhes overexpression activates autophagy. These effects are independent of mTOR and opposite in the direction predicted by the known activation of mTOR by Rhes. Rhes robustly binds the autophagy regulator Beclin-1, decreasing its inhibitory interaction with Bcl-2 independent of JNK-1 signaling. Finally, co-expression of mHtt blocks Rhes-induced autophagy activation. Thus, the isolated pathology and delayed onset of HD may reflect the striatal-selective expression and changes in autophagic activity of Rhes.

  5. Activation of mTOR: a culprit of Alzheimer’s disease?

    PubMed Central

    Cai, Zhiyou; Chen, Guanghui; He, Wenbo; Xiao, Ming; Yan, Liang-Jun

    2015-01-01

    Alzheimer’s disease (AD) is characterized by cognitive impairment in clinical presentation, and by β-amyloid (Aβ) production and the hyper-phosphorylation of tau in basic research. More highlights demonstrate that the activation of the mammalian target of rapamycin (mTOR) enhances Aβ generation and deposition by mod