WorldWideScience

Sample records for ageing exacerbates damage

  1. Obesity in Aging Exacerbates Blood–Brain Barrier Disruption, Neuroinflammation, and Oxidative Stress in the Mouse Hippocampus: Effects on Expression of Genes Involved in Beta-Amyloid Generation and Alzheimer’s Disease

    OpenAIRE

    Tucsek, Zsuzsanna; Toth, Peter; Sosnowska, Danuta; Gautam, Tripti; Mitschelen, Matthew; Koller, Akos; Szalai, Gabor; Sonntag, William E.; Ungvari, Zoltan; Csiszar, Anna

    2013-01-01

    There is growing evidence that obesity has deleterious effects on the brain and cognitive function in the elderly population. However, the specific mechanisms through which aging and obesity interact to promote cognitive decline remain unclear. To test the hypothesis that aging exacerbates obesity-induced cerebromicrovascular damage and neuroinflammation, we compared young (7 months) and aged (24 months) high fat diet–fed obese C57BL/6 mice. Aging exacerbated obesity-induced systemic inflamma...

  2. Aging Exacerbates Extrapyramidal Motor Signs in the Era of HAART

    OpenAIRE

    Valcour, Victor; Watters, Michael R.; Williams, Andrew E.; Sacktor, Ned; McMurtray, Aaron; Shikuma, Cecilia

    2008-01-01

    The phenotype of HIV-associated Neurocognitive Disorders (HAND) in the developed world has changed with the broad institution of HAART and with aging of the HIV+ population. Extrapyramidal motor signs were a prominent feature of HAND as defined in the early stages of the epidemic but has not be re-evaluated in the era of HAART. Moreover, the contribution of aging to extrapyramidal motor signs in the context of HIV remains undefined. We examined these questions among the 229 HIV+ participants ...

  3. NOX Activity in Brain Aging: Exacerbation by High Fat Diet

    OpenAIRE

    Bruce-Keller, Annadora J.; White, Christy L.; Gupta, Sunita; Knight, Alecia G.; Pistell, Paul J.; Ingram, Donald K.; Morrison, Christopher D.; Keller, Jeffrey N.

    2010-01-01

    This study describes how age and high fat diet affect the profile of NADPH oxidase (NOX). Specifically, NOX activity and subunit expression were evaluated in the frontal cerebral cortex of 7-, 16-, and 24-month old mice following a 4-month exposure to either Western diet (WD, 41% calories from fat) or very high fat lard diet (VHFD, 60% calories from fat). Data reveal a significant effect of age in on NOX activity, and show that NOX activity was only increased by VHFD, and only in 24-month old...

  4. Chronic Glucocorticoid Hypersecretion in Cushing's Syndrome Exacerbates Cognitive Aging

    Science.gov (United States)

    Michaud, Kathy; Forget, Helene; Cohen, Henri

    2009-01-01

    Cumulative exposure to glucocorticoid hormones (GC) over the lifespan has been associated with cognitive impairment and may contribute to physical and cognitive degeneration in aging. The objective of the present study was to examine whether the pattern of cognitive deficits in patients with Cushing's syndrome (CS), a disorder characterized by…

  5. Predicting an asthma exacerbation in children 2 to 5 years of age

    DEFF Research Database (Denmark)

    Swern, A.S.; Tozzi, C.A.; Knorr, B.;

    2008-01-01

    an exacerbation. Caregiver-reported information (daytime cough, breathing difficulties, limitation of activity, nighttime cough or awakening, daytime and nighttime beta2-agonist use) were analyzed using general estimating equations with an exchangeable within-subject log odds ratio regression...... structure to identify predictors of an exacerbation. RESULTS: Average symptom scores and beta2-agonist use increased significantly before exacerbation but at different rates. A combination of daytime cough and wheeze and nighttime beta2-agonist use 1 day before the exacerbation was identified as strongly...... predictive of an exacerbation. These methods predicted 149 (66.8%) of the exacerbations with a very low false-positive rate of 14.2%. CONCLUSIONS: No individual symptom was predictive of an imminent asthma exacerbation, but a combination of increased daytime cough, daytime wheeze, and nighttime beta2-agonist...

  6. A CONTINUUM DAMAGE MODEL OF AGING CONCRETE

    Institute of Scientific and Technical Information of China (English)

    Zhao Zhenyang; Xie Huicai; Xu Tao; Yu Jie; Cai Changan

    2001-01-01

    There is up to now no constitutive model in the current theories of CDM that could give a description for the degradation of aging concrete. The two internal state variables β and ω are introduced in this paper. β is called cohesion variable as an additional kinematic parameter, reflecting the cohesion state among material particles. ω is called damage factor for micro-defects such as voids.Then a damage model and a series of constitutive equations are developed on Continuum Mechanics.The model proposed could give a valid description for the whole-course-degradation of aging concrete due tochemical and mechanical actions. Finally, the validity of the model is evaluated by an example and experimental results.

  7. Aging Exacerbates Depressive-like Behavior in Mice in Response to Activation of the Peripheral Innate Immune System

    OpenAIRE

    Godbout, Jonathan P.; Moreau, Maïté; Lestage, Jacques; Chen, Jing; Sparkman, Nathan L; O’Connor, Jason; Castanon, Nathalie; Kelley, Keith W.; Dantzer, Robert; Johnson, Rodney W.

    2007-01-01

    Exposure to peripheral infections may be permissive to cognitive and behavioral complications in the elderly. We have reported that peripheral stimulation of the innate immune system with lipopolysaccharide (LPS) causes an exaggerated neuroinflammatory response and prolonged sickness behavior in aged BALB/c mice. Because LPS also causes depressive behavior, the purpose of this study was to determine whether aging is associated with an exacerbated depressive-like response. We confirmed that LP...

  8. Predicting an asthma exacerbation in children 2 to 5 years of age

    DEFF Research Database (Denmark)

    Swern, Arlene S; Tozzi, Carol A; Knorr, Barbara;

    2008-01-01

    an exacerbation. Caregiver-reported information (daytime cough, breathing difficulties, limitation of activity, nighttime cough or awakening, daytime and nighttime beta2-agonist use) were analyzed using general estimating equations with an exchangeable within-subject log odds ratio regression...

  9. Low concentrations of isothiocyanates protect mesenchymal stem cells from oxidative injuries, while high concentrations exacerbate DNA damage.

    Science.gov (United States)

    Zanichelli, Fulvia; Capasso, Stefania; Di Bernardo, Giovanni; Cipollaro, Marilena; Pagnotta, Eleonora; Cartenì, Maria; Casale, Fiorina; Iori, Renato; Giordano, Antonio; Galderisi, Umberto

    2012-09-01

    Isothiocyanates (ITCs) are molecules naturally present in many cruciferous vegetables (broccoli, black radish, daikon radish, and cauliflowers). Several studies suggest that cruciferous vegetable consumption may reduce cancer risk and slow the aging process. To investigate the effect of ITCs on cellular DNA damage, we evaluated the effects of two different ITCs [sulforaphane (SFN) and raphasatin (RPS)] on the biology of human mesenchymal stem cells (MSCs), which, in addition to their ability to differentiate into mesenchymal tissues, contribute to the homeostatic maintenance of many organs. The choice of SFN and RPS relies on two considerations: they are among the most popular cruciferous vegetables in the diet of western and eastern countries, respectively, and their bioactive properties may differ since they possess specific molecular moiety. Our investigation evidenced that MSCs incubated with low doses of SFN and RPS show reduced in vitro oxidative stress. Moreover, these cells are protected from oxidative damages induced by hydrogen peroxide, while no protection was evident following treatment with the UV ray of a double strand DNA damaging drug, such as doxorubicin. High concentrations of both ITCs induced cytotoxic effects in MSC cultures and further increased DNA damage induced by peroxides. In summary, our study suggests that ITCs, at low doses, may contribute to slowing the aging process related to oxidative DNA damage. Moreover, in cancer treatment, low doses of ITCs may be used as an adjuvant to reduce chemotherapy-induced oxidative stress, while high doses may synergize with anticancer drugs to promote cell DNA damage. PMID:22684843

  10. Maternal inflammation linearly exacerbates offspring age-related changes of spatial learning and memory, and neurobiology until senectitude.

    Science.gov (United States)

    Li, Xue-Wei; Cao, Lei; Wang, Fang; Yang, Qi-Gang; Tong, Jing-Jing; Li, Xue-Yan; Chen, Gui-Hai

    2016-06-01

    Maternal inflammation during pregnancy can elevate the risk of neurodegenerative disorders in offspring. However, how it affects age-related impairments of spatial learning and memory and changes in the neurobiological indictors in the offspring in later adulthood is still elusive. In this study, the CD-1 mice with maternal gestational inflammation due to receiving lipopolysaccharide (LPS, i.p. 50 or 25μg/kg) were divided into 3-, 12-, 18-, and 22-month-old groups. The spatial learning and memory were evaluated using a six-radial arm water maze and the levels of presynaptic proteins (synaptotagmin-1 and syntaxin-1) and histone acetylation (H3K9ac and H4K8ac) in the dorsal hippocampus were detected using the immunohistochemical method. The results indicated that there were significant age-related impairments of spatial learning and memory, decreased levels of H4K8ac, H3K9ac, and syntaxin-1, and increased levels of synaptotagmin-1 in the offspring mice from 12 months old to 22 months old compared to the same-age controls. Maternal LPS treatment significantly exacerbated the offspring impairments of spatial learning and memory, the reduction of H3K9ac, H4K8ac, and syntaxin-1, and the increment of synaptotagmin-1 from 12 months old to 22 months old compared to the same-age control groups. The changes in the neurobiological indicators significantly correlated with the impairments of spatial learning and memory. Furthermore, this correlation, besides the age and LPS-treatment effects, also showed a dose-dependent effect. Our results suggest that maternal inflammation during pregnancy could exacerbate age-related impairments of spatial learning and memory, and neurobiochemical indicators in the offspring CD-1 mice from midlife to senectitude. PMID:26992827

  11. Aging and oxidatively damaged nuclear DNA in animal organs

    DEFF Research Database (Denmark)

    Møller, Peter; Løhr, Mille; Folkmann, Janne K;

    2010-01-01

    Oxidative stress is considered to contribute to aging and is associated with the generation of oxidatively damaged DNA, including 8-oxo-7,8-dihydroguanine. We have identified 69 studies that have measured the level of oxidatively damaged DNA in organs of animals at various ages. In general, organs...... with limited cell proliferation, i.e., liver, kidney, brain, heart, pancreas, and muscle, tended to show accumulation of DNA damage with age, whereas organs with highly proliferating cells, such as intestine, spleen, and testis, showed more equivocal or no effect of age. A restricted analysis of studies...

  12. Short-lived diabetes in the young-adult ZDF rat does not exacerbate neuronal Ca(2+) biomarkers of aging.

    Science.gov (United States)

    Maimaiti, Shaniya; DeMoll, Chris; Anderson, Katie L; Griggs, Ryan B; Taylor, Bradley K; Porter, Nada M; Thibault, Olivier

    2015-09-24

    Results from clinical studies provide evidence that cognitive changes relatively late in life may be traced to antecedent conditions including diabetes, obesity, a sedentary lifestyle, and an atherogenic diet. As such, several traits of Type 2 diabetes (T2DM) could be considered pathogenic factors of aging, contributing to age-dependent cognitive decline and our susceptibility to Alzheimer's disease. It appears that both the duration of metabolic condition and the age of the individual, together can contribute to the potential impact on peripheral as well as brain health. Because of robust evidence that in animal models of aging, Ca(2+) dysregulation alters neuronal health, synaptic plasticity, and learning and memory processes, we tested the hypothesis that peripheral metabolic dysregulation could exacerbate Ca(2+) dysfunction in hippocampal CA1 neurons. Using intracellular/ extracellular electrophysiological and Ca(2+) imaging techniques, we show that Ca(2+)levels at rest or during synaptic stimulation, the Ca(2+)-dependent afterhyperpolarization, baseline field potentials, and short-term synaptic plasticity were not significantly altered in young-adult male Zucker diabetic fatty rats compare to their lean counterparts. Our observations suggest that early phases of T2DM characterized by high levels of glucose and insulin may be too transient to alter hippocampal CA1 physiology in this animal model of diabetes. These results are supported by clinical data showing that longer T2DM duration can have greater negative impact on cognitive functions. This article is part of a Special Issue entitled SI: Brain and Memory. PMID:25451110

  13. Brain Damage in School Age Children.

    Science.gov (United States)

    Haywood, H. Carl, Ed.

    The product of a professional workshop, 10 papers discuss brain damage. An introduction to clinical neuropsychology is presented by H. Carl Haywood. A section on neurological foundations includes papers on the organization of the central nervous system by Jack T. Tapp and Lance L. Simpson, on epilepsy by Angela T. Folsom, and on organic language…

  14. Age-Dependent Reductions in Mitochondrial Respiration are Exacerbated by Calcium in the Female Rat Heart

    OpenAIRE

    Hunter, J. Craig; Machikas, Alexandra M.; Korzick, Donna H.

    2012-01-01

    Cardiovascular disease mortality increases rapidly following menopause by poorly defined mechanisms. Since mitochondrial function and Ca2+ sensitivity are important regulators of cell death following myocardial ischemia, we sought to determine if aging and/or estrogen deficiency (ovx) increased mitochondrial Ca2+ sensitivity. Mitochondrial respiration was measured in ventricular mitochondria isolated from adult (6mo; n=26) and aged (24mo; n=25), intact or ovariectomized female rats using the ...

  15. Diabetes exacerbates amyloid and neurovascular pathology in aging-accelerated mice

    OpenAIRE

    Currais, Antonio; Prior, Marguerite; Lo, David; Jolivalt, Corinne; Schubert, David; Maher, Pamela

    2012-01-01

    Mounting evidence supports a link between diabetes, cognitive dysfunction and aging. However, the physiological mechanisms by which diabetes impacts brain function and cognition are not fully understood. To determine how diabetes contributes to cognitive dysfunction and age-associated pathology, we used streptozotocin to induce type 1 diabetes (T1D) in senescence-accelerated prone 8 (SAMP8) and senescence-resistant 1 (SAMR1) mice. Contextual fear conditioning demonstrated that T1D resulted in...

  16. Epoetin beta pegol alleviates oxidative stress and exacerbation of renal damage from iron deposition, thereby delaying CKD progression in progressive glomerulonephritis rats.

    Science.gov (United States)

    Hirata, Michinori; Tashiro, Yoshihito; Aizawa, Ken; Kawasaki, Ryohei; Shimonaka, Yasushi; Endo, Koichi

    2015-12-01

    The increased deposition of iron in the kidneys that occurs with glomerulopathy hinders the functional and structural recovery of the tubules and promotes progression of chronic kidney disease (CKD). Here, we evaluated whether epoetin beta pegol (continuous erythropoietin receptor activator: CERA), which has a long half-life in blood and strongly suppresses hepcidin-25, exerts renoprotection in a rat model of chronic progressive glomerulonephritis (cGN). cGN rats showed elevated urinary total protein excretion (uTP) and plasma urea nitrogen (UN) from day 14 after the induction of kidney disease (day 0) and finally declined into end-stage kidney disease (ESKD), showing reduced creatinine clearance with glomerulosclerosis, tubular dilation, and tubulointerstitial fibrosis. A single dose of CERA given on day 1, but not on day 16, alleviated increasing uTP and UN, thereby delaying ESKD. In the initial disease phase, CERA significantly suppressed urinary 8-OHdG and liver-type fatty acid-binding protein (L-FABP), a tubular damage marker. CERA also inhibited elevated plasma hepcidin-25 levels and alleviated subsequent iron accumulation in kidneys in association with elevated urinary iron excretion and resulted in alleviation of growth of Ki67-positive tubular and glomerular cells. In addition, at day 28 when the exacerbation of uTP occurs, a significant correlation was observed between iron deposition in the kidney and urinary L-FABP. In our study, CERA mitigated increasing kidney damage, thereby delaying CKD progression in this glomerulonephritis rat model. Alleviation by CERA of the exacerbation of kidney damage could be attributable to mitigation of tubular damage that might occur with lowered iron deposition in tubules. PMID:26634903

  17. Liver damage and systemic inflammatory responses are exacerbated by the genetic deletion of CD39 in total hepatic ischemia

    OpenAIRE

    SUN, XIAOFENG; IMAI, MASATO; Nowak-Machen, Martina; Guckelberger, Olaf; Enjyoji, Keiichi; Wu, Yan; Khalpey, Zain; Berberat, Pascal; Munasinghe, Jeeva; Robson, Simon Christopher

    2011-01-01

    Liver ischemia reperfusion injury is associated with both local damage to the hepatic vasculature and systemic inflammatory responses. CD39 is the dominant vascular endothelial cell ectonucleotidase and rapidly hydrolyses both adenosine triphosphate (ATP) and adenosine diphosphate to adenosine monophosphate. These biochemical properties, in tandem with 5′-nucleotidases, generate adenosine and potentially illicit inflammatory vascular responses and thrombosis. We have evaluated the role of CD3...

  18. DNA Damage: A Main Determinant of Vascular Aging.

    Science.gov (United States)

    Bautista-Niño, Paula K; Portilla-Fernandez, Eliana; Vaughan, Douglas E; Danser, A H Jan; Roks, Anton J M

    2016-01-01

    Vascular aging plays a central role in health problems and mortality in older people. Apart from the impact of several classical cardiovascular risk factors on the vasculature, chronological aging remains the single most important determinant of cardiovascular problems. The causative mechanisms by which chronological aging mediates its impact, independently from classical risk factors, remain to be elucidated. In recent years evidence has accumulated that unrepaired DNA damage may play an important role. Observations in animal models and in humans indicate that under conditions during which DNA damage accumulates in an accelerated rate, functional decline of the vasculature takes place in a similar but more rapid or more exaggerated way than occurs in the absence of such conditions. Also epidemiological studies suggest a relationship between DNA maintenance and age-related cardiovascular disease. Accordingly, mouse models of defective DNA repair are means to study the mechanisms involved in biological aging of the vasculature. We here review the evidence of the role of DNA damage in vascular aging, and present mechanisms by which genomic instability interferes with regulation of the vascular tone. In addition, we present potential remedies against vascular aging induced by genomic instability. Central to this review is the role of diverse types of DNA damage (telomeric, non-telomeric and mitochondrial), of cellular changes (apoptosis, senescence, autophagy), mediators of senescence and cell growth (plasminogen activator inhibitor-1 (PAI-1), cyclin-dependent kinase inhibitors, senescence-associated secretory phenotype (SASP)/senescence-messaging secretome (SMS), insulin and insulin-like growth factor 1 (IGF-1) signaling), the adenosine monophosphate-activated protein kinase (AMPK)-mammalian target of rapamycin (mTOR)-nuclear factor kappa B (NFκB) axis, reactive oxygen species (ROS) vs. endothelial nitric oxide synthase (eNOS)-cyclic guanosine monophosphate (c

  19. Connecting the Dots: From DNA Damage and Repair to Aging.

    Science.gov (United States)

    Pan, Mei-Ren; Li, Kaiyi; Lin, Shiaw-Yih; Hung, Wen-Chun

    2016-01-01

    Mammalian cells evolve a delicate system, the DNA damage response (DDR) pathway, to monitor genomic integrity and to prevent the damage from both endogenous end exogenous insults. Emerging evidence suggests that aberrant DDR and deficient DNA repair are strongly associated with cancer and aging. Our understanding of the core program of DDR has made tremendous progress in the past two decades. However, the long list of the molecules involved in the DDR and DNA repair continues to grow and the roles of the new "dots" are under intensive investigation. Here, we review the connection between DDR and DNA repair and aging and discuss the potential mechanisms by which deficient DNA repair triggers systemic effects to promote physiological or pathological aging. PMID:27164092

  20. Connecting the Dots: From DNA Damage and Repair to Aging

    Directory of Open Access Journals (Sweden)

    Mei-Ren Pan

    2016-05-01

    Full Text Available Mammalian cells evolve a delicate system, the DNA damage response (DDR pathway, to monitor genomic integrity and to prevent the damage from both endogenous end exogenous insults. Emerging evidence suggests that aberrant DDR and deficient DNA repair are strongly associated with cancer and aging. Our understanding of the core program of DDR has made tremendous progress in the past two decades. However, the long list of the molecules involved in the DDR and DNA repair continues to grow and the roles of the new “dots” are under intensive investigation. Here, we review the connection between DDR and DNA repair and aging and discuss the potential mechanisms by which deficient DNA repair triggers systemic effects to promote physiological or pathological aging.

  1. DNA damage and repair in age-related macular degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Szaflik, Jacek P. [Department of Ophthalmology, Medical University of Warsaw and Samodzielny Publiczny Szpital Okulistyczny, Sierakowskiego 13, 03-710 Warsaw (Poland); Janik-Papis, Katarzyna; Synowiec, Ewelina; Ksiazek, Dominika [Department of Molecular Genetics, University of Lodz, Banacha 12/16, 90-237 Lodz (Poland); Zaras, Magdalena [Department of Ophthalmology, Medical University of Warsaw and Samodzielny Publiczny Szpital Okulistyczny, Sierakowskiego 13, 03-710 Warsaw (Poland); Wozniak, Katarzyna [Department of Molecular Genetics, University of Lodz, Banacha 12/16, 90-237 Lodz (Poland); Szaflik, Jerzy [Department of Ophthalmology, Medical University of Warsaw and Samodzielny Publiczny Szpital Okulistyczny, Sierakowskiego 13, 03-710 Warsaw (Poland); Blasiak, Janusz, E-mail: januszb@biol.uni.lodz.pl [Department of Molecular Genetics, University of Lodz, Banacha 12/16, 90-237 Lodz (Poland)

    2009-10-02

    Age-related macular degeneration (AMD) is a retinal degenerative disease that is the main cause of vision loss in individuals over the age of 55 in the Western world. Clinically relevant AMD results from damage to the retinal pigment epithelial (RPE) cells thought to be mainly caused by oxidative stress. The stress also affects the DNA of RPE cells, which promotes genome instability in these cells. These effects may coincide with the decrease in the efficacy of DNA repair with age. Therefore individuals with DNA repair impaired more than average for a given age may be more susceptible to AMD if oxidative stress affects their RPE cells. This may be helpful in AMD risk assessment. In the present work we determined the level of basal (measured in the alkaline comet assay) endogenous and endogenous oxidative DNA damage, the susceptibility to exogenous mutagens and the efficacy of DNA repair in lymphocytes of 100 AMD patients and 110 age-matched individuals without visual disturbances. The cells taken from AMD patients displayed a higher extent of basal endogenous DNA damage without differences between patients of dry and wet forms of the disease. DNA double-strand breaks did not contribute to the observed DNA damage as checked by the neutral comet assay and pulsed field gel electrophoresis. The extent of oxidative modification to DNA bases was grater in AMD patients than in the controls, as probed by DNA repair enzymes NTH1 and Fpg. Lymphocytes from AMD patients displayed a higher sensitivity to hydrogen peroxide and UV radiation and repaired lesions induced by these factors less effectively than the cells from the control individuals. We postulate that the impaired efficacy of DNA repair may combine with enhanced sensitivity of RPE cells to blue and UV lights, contributing to the pathogenesis of AMD.

  2. DNA damage and repair in age-related macular degeneration

    International Nuclear Information System (INIS)

    Age-related macular degeneration (AMD) is a retinal degenerative disease that is the main cause of vision loss in individuals over the age of 55 in the Western world. Clinically relevant AMD results from damage to the retinal pigment epithelial (RPE) cells thought to be mainly caused by oxidative stress. The stress also affects the DNA of RPE cells, which promotes genome instability in these cells. These effects may coincide with the decrease in the efficacy of DNA repair with age. Therefore individuals with DNA repair impaired more than average for a given age may be more susceptible to AMD if oxidative stress affects their RPE cells. This may be helpful in AMD risk assessment. In the present work we determined the level of basal (measured in the alkaline comet assay) endogenous and endogenous oxidative DNA damage, the susceptibility to exogenous mutagens and the efficacy of DNA repair in lymphocytes of 100 AMD patients and 110 age-matched individuals without visual disturbances. The cells taken from AMD patients displayed a higher extent of basal endogenous DNA damage without differences between patients of dry and wet forms of the disease. DNA double-strand breaks did not contribute to the observed DNA damage as checked by the neutral comet assay and pulsed field gel electrophoresis. The extent of oxidative modification to DNA bases was grater in AMD patients than in the controls, as probed by DNA repair enzymes NTH1 and Fpg. Lymphocytes from AMD patients displayed a higher sensitivity to hydrogen peroxide and UV radiation and repaired lesions induced by these factors less effectively than the cells from the control individuals. We postulate that the impaired efficacy of DNA repair may combine with enhanced sensitivity of RPE cells to blue and UV lights, contributing to the pathogenesis of AMD.

  3. Statin-induced myotoxicity is exacerbated by aging: A biophysical and molecular biology study in rats treated with atorvastatin.

    Science.gov (United States)

    Camerino, Giulia Maria; De Bellis, Michela; Conte, Elena; Liantonio, Antonella; Musaraj, Kejla; Cannone, Maria; Fonzino, Adriano; Giustino, Arcangela; De Luca, Annamaria; Romano, Rossella; Camerino, Claudia; Laghezza, Antonio; Loiodice, Fulvio; Desaphy, Jean-Francois; Conte Camerino, Diana; Pierno, Sabata

    2016-09-01

    Statin-induced skeletal muscle damage in rats is associated to the reduction of the resting sarcolemmal chloride conductance (gCl) and ClC-1 chloride channel expression. These drugs also affect the ClC-1 regulation by increasing protein kinase C (PKC) activity, which phosphorylate and close the channel. Also the intracellular resting calcium (restCa) level is increased. Similar alterations are observed in skeletal muscles of aged rats, suggesting a higher risk of statin myotoxicity. To verify this hypothesis, we performed a 4-5-weeks atorvastatin treatment of 24-months-old rats to evaluate the ClC-1 channel function by the two-intracellular microelectrodes technique as well as transcript and protein expression of different genes sensitive to statins by quantitative real-time-PCR and western blot analysis. The restCa was measured using FURA-2 imaging, and histological analysis of muscle sections was performed. The results show a marked reduction of resting gCl, in agreement with the reduced ClC-1 mRNA and protein expression in atorvastatin-treated aged rats, with respect to treated adult animals. The observed changes in myocyte-enhancer factor-2 (MEF2) expression may be involved in ClC-1 expression changes. The activity of PKC was also increased and further modulate the gCl in treated aged rats. In parallel, a marked reduction of the expression of glycolytic and mitochondrial enzymes demonstrates an impairment of muscle metabolism. No worsening of restCa or histological features was found in statin-treated aged animals. These findings suggest that a strong reduction of gCl and alteration of muscle metabolism coupled to muscle atrophy may contribute to the increased risk of statin-induced myopathy in the elderly. PMID:27377005

  4. DNA Damage Response in Hematopoietic Stem Cell Ageing.

    Science.gov (United States)

    Li, Tangliang; Zhou, Zhong-Wei; Ju, Zhenyu; Wang, Zhao-Qi

    2016-06-01

    Maintenance of tissue-specific stem cells is vital for organ homeostasis and organismal longevity. Hematopoietic stem cells (HSCs) are the most primitive cell type in the hematopoietic system. They divide asymmetrically and give rise to daughter cells with HSC identity (self-renewal) and progenitor progenies (differentiation), which further proliferate and differentiate into full hematopoietic lineages. Mammalian ageing process is accompanied with abnormalities in the HSC self-renewal and differentiation. Transcriptional changes and epigenetic modulations have been implicated as the key regulators in HSC ageing process. The DNA damage response (DDR) in the cells involves an orchestrated signaling pathway, consisting of cell cycle regulation, cell death and senescence, transcriptional regulation, as well as chromatin remodeling. Recent studies employing DNA repair-deficient mouse models indicate that DDR could intrinsically and extrinsically regulate HSC maintenance and play important roles in tissue homeostasis of the hematopoietic system. In this review, we summarize the current understanding of how the DDR determines the HSC fates and finally contributes to organismal ageing. PMID:27221660

  5. DNA Damage Response in Hematopoietic Stem Cell Ageing

    Institute of Scientific and Technical Information of China (English)

    Tangliang Li; Zhong-Wei Zhou; Zhenyu Ju; Zhao-Qi Wang

    2016-01-01

    Maintenance of tissue-specific stem cells is vital for organ homeostasis and organismal longevity. Hematopoietic stem cells (HSCs) are the most primitive cell type in the hematopoietic system. They divide asymmetrically and give rise to daughter cells with HSC identity (self-renewal) and progenitor progenies (differentiation), which further proliferate and differentiate into full hematopoietic lineages. Mammalian ageing process is accompanied with abnormalities in the HSC self-renewal and differentiation. Transcriptional changes and epigenetic modulations have been implicated as the key regulators in HSC ageing process. The DNA damage response (DDR) in the cells involves an orchestrated signaling pathway, consisting of cell cycle regulation, cell death and senescence, transcriptional regulation, as well as chromatin remodeling. Recent studies employ-ing DNA repair-deficient mouse models indicate that DDR could intrinsically and extrinsically reg-ulate HSC maintenance and play important roles in tissue homeostasis of the hematopoietic system. In this review, we summarize the current understanding of how the DDR determines the HSC fates and finally contributes to organismal ageing.

  6. Isolation Housing Exacerbates Alzheimer’s Disease-Like Pathophysiology in Aged APP/PS1 Mice

    OpenAIRE

    Huang, Huang; Wang, Linmei; Cao, Min; Marshall, Charles; Gao, Junying; XIAO, NA; Hu, Gang; Xiao, Ming

    2015-01-01

    Background: Alzheimer’s disease is a neurodegenerative disease characterized by gradual declines in social, cognitive, and emotional functions, leading to a loss of expected social behavior. Social isolation has been shown to have adverse effects on individual development and growth as well as health and aging. Previous experiments have shown that social isolation causes an early onset of Alzheimer’s disease-like phenotypes in young APP695/PS1-dE9 transgenic mice. However, the interactions be...

  7. DNA damage markers in dermal fibroblasts in vitro reflect chronological donor age

    DEFF Research Database (Denmark)

    Waaijer, Mariëtte E C; Croco, Eleonora; Westendorp, Rudi G J; Slagboom, P Eline; Sedivy, John M; Lorenzini, Antonello; Maier, Andrea B

    2016-01-01

    The aging process is accompanied by an accumulation of cellular damage, which compromises the viability and function of cells and tissues. We aim to further explore the association between in vitro DNA damage markers and the chronological age of the donor, as well as long-lived family membership...... damage markers and long-lived family membership or cardiovascular disease. Results were comparable when fibroblasts were stressed in vitro with rotenone. In conclusion, we found that DNA damage foci of cultured fibroblasts are significantly associated with the chronological age, but not biological age...

  8. Post-Stroke Infections Exacerbate Ischemic Brain Injury in Middle-Aged Rats: Immunomodulation and Neuroprotection by Progesterone

    OpenAIRE

    Yousuf, Seema; Atif, Fahim; Sayeed, Iqbal; Wang, Jun; Stein, Donald G.

    2012-01-01

    We investigated the effect of delayed, prolonged systemic inflammation on stroke outcomes and progesterone (P4) neuroprotection in middle-aged rats. After transient middle cerebral artery occlusion/reperfusion (MCAO) surgery, rats received P4 (8 or 16 mg/kg) or vehicle injections at 2h, 6h and every 24h until day 7 post-occlusion. At 24h post-injury systemic inflammation was induced by giving 3 doses of lipopolysaccharide (LPS; 50 mg/kg, at 4h intervals) to model post-stroke infections. We me...

  9. Exacerbations of asthma during pregnancy

    DEFF Research Database (Denmark)

    Ali, Zarqa; Hansen, A V; Ulrik, C S

    2016-01-01

    Asthma is common among pregnant women, and the incidence of asthma exacerbations during pregnancy is high. This literature review provides an overview of the impact of exacerbations of asthma during pregnancy on pregnancy-related complications. The majority of published retrospective studies reveal...... that asthma exacerbations during pregnancy increase the risk of pre-eclampsia, gestational diabetes, placental abruption and placenta praevia. Furthermore, these women also have higher risk for breech presentation, haemorrhage, pulmonary embolism, caesarean delivery, maternal admission to the intensive...... care unit and longer postpartum hospital stay. Asthma has been associated with increased risk of intrauterine growth retardation, small-for-gestational age, low birth weight, infant hypoglycaemia and preterm birth, but more recent prospective studies have not revealed significant associations with...

  10. Contact damage in artificially aged 3Y-TZP

    Energy Technology Data Exchange (ETDEWEB)

    Armas Sancho, Z de; Jimenez-Pique, E; Mestra, A; Anglada, M, E-mail: zamir.de.armas@upc.edu [Center for Structural Integrity and Reliability of Materials, CIEFMA Dpt. Materials Science and Metallurgical Engineering Universitat Politecnica de Catalunya, UPC Av. Diagonal 647, 08028 Barcelona (Spain)

    2009-09-15

    The behaviour of hydrothermal degraded 3% molar yttria stabilised zirconia under monotonic spherical indentation has been studied. The investigation is focused mainly on analysing the response under spherical indentation in terms of the transformed monoclinic surface layer that appears after hydrothermal degradation. The mechanisms of damage are ring and cone cracking, similarly as in as sintered specimens. The permanent damage induced in degraded specimens is always larger than in the as sintered specimens. The 'plastic' damage measured by the value of the indentation strain in degraded specimens is larger than in as sintered specimens at the same indentation pressure. The critical contact load to induce ring cracking is determined and it is found that in degraded specimens its value is lower than in as sintered specimens. The results are discussed in terms of elastic properties and microstructure of the degraded layer.

  11. Preventing and Lessening Exacerbations of Asthma in School-aged children Associated with a New Term (PLEASANT): Recruiting Primary Care Research Sites–the PLEASANT experience

    Science.gov (United States)

    Horspool, Michelle J; Julious, Steven A; Mooney, Cara; May, Robin; Sully, Ben; Smithson, W Henry

    2015-01-01

    Background: Recruitment of general practices and their patients into research studies is frequently reported as a challenge. The Preventing and Lessening Exacerbations of Asthma in School-aged children Associated with a New Term (PLEASANT) trial recruited 142 general practices, across England and Wales and delivered the study intervention to time and target. Aims: To describe the process of recruitment used within the cluster randomised PLEASANT trial and present results on factors that influenced recruitment. Methods: Data were collected on the number of and types of contact used to gain expression of interest and subsequent randomisation into the PLEASANT trial. Practice size and previous research experience were also collected. Results: The mean number of contacts required to gain expression of interest were m=3.01 (s.d. 1.6) and total number of contacts from initial invitation to randomisation m=6.8 (s.d. 3.5). Previous randomised controlled trial involvement (hazard ratio (HR)=1.81 (confidence interval (CI) 95%, 1.55–2.11) P<0.001) and number of studies a practice had previously engaged in (odds ratio (OR) 1.91 (CI 95%, (1.52–2.42)) P<0.001), significantly influenced whether a practice would participate in PLEASANT. Practice size was not a significant deciding factor (OR=1.04 (95% CI 0.99–1.08) P=0.137). Conclusions: Recruitment to time and target can be achieved in general practice. The amount of resource required for site recruitment should not, however, be underestimated and multiple strategies for contacting practices should be considered. General practitioners with more research experience are more likely to participate in studies. PMID:26562491

  12. Caveolar vesicles generate DNA damage and perpetuate cellular aging

    Institute of Scientific and Technical Information of China (English)

    Keith Wheaton

    2011-01-01

    @@ The replicative limit of human fibroblasts has long provided a model to assess the molecular mechanisms underlying cellular aging [1].In culture, fibroblasts which reach the end of their proliferative lifespan acquire profound molecular changes that limit their response to growth factors, and cause permanent exit from the cell cycle [2].

  13. The effects of male age on sperm DNA damage in healthy non-smokers

    Energy Technology Data Exchange (ETDEWEB)

    Schmid, T; Eskenazi, B; Baumgartner, A; Marchetti, F; Young, S; Weldon, R; Anderson, D; Wyrobek, A

    2006-03-08

    The trend for men to have children at older ages raises concerns that advancing age may increase the production of genetically defective sperm, increasing the risks of transmitting germ-line mutations. We investigated the associations between male age and sperm DNA damage and the influence of several lifestyle factors in a healthy non-clinical group of 80 non-smokers (age: 22-80) with no known fertility problems using the sperm Comet analyses. The average percent of DNA that migrated out of the sperm nucleus under alkaline electrophoresis increased with age (0.18% per year, p=0.006); but there was no age association for damage measured under neutral conditions (p=0.7). Men who consumed >3 cups coffee per day had {approx}20% higher % tail DNA under neutral but not alkaline conditions compared to men who consumed no caffeine (p=0.005). Our findings indicate that (a) older men have increased sperm DNA damage associated with alkali-labile sites or single-strand DNA breaks, and (b) independent of age, men with substantial daily caffeine consumption have increased sperm DNA damage associated with double-strand DNA breaks. DNA damage in sperm can be converted to chromosomal aberrations and gene mutations after fertilization increasing the risks for developmental defects and genetic diseases among offspring.

  14. Oxidative damage and age-related macular degeneration

    OpenAIRE

    Winkler, Barry S.; Boulton, Michael E.; Gottsch, John D.; Sternberg, Paul

    1999-01-01

    This article provides current information on the potential role of oxidation in relation to age-related macular degeneration (AMD). The emphasis is placed on the generation of oxidants and free radicals and the protective effects of antioxidants in the outer retina, with specific emphasis on the photoreceptor cells, the retinal pigment epithelium and the choriocapillaris. The starting points include a discussion and a definition of what radicals are, their endogenous sources, how they react, ...

  15. Aging, Loss-of-Coolant Accident (LOCA), and high potential testing of damaged cables

    International Nuclear Information System (INIS)

    Experiments were conducted to assess the effects of high potential testing of cables and to assess the survivability of aged and damaged cables under Loss-of-Coolant Accident (LOCA) conditions. High potential testing at 240 Vdc/mil on undamaged cables suggested that no damage was incurred on the selected virgin cables. During aging and LOCA testing, Okonite ethylene propylene rubber (EPR) cables with a bonded jacket experienced unexpected failures. The failures appear to be primarily related to the level of thermal aging and the presence of a bonded jacket that ages more rapidly than the insulation. For Brand Rex crosslinked polyolefin (XLPO) cables, the results suggest that 7 mils of insulation remaining should give the cables a high probability of surviving accident exposure following aging. The voltage necessary to detect when 7 mils of insulation remain on unaged Brand Rex cables is approximately 35 kVdc. This voltage level would almost certainly be unacceptable to a utility for use as a damage assessment tool. However, additional tests indicated that a 35 kvdc voltage application would not damage virgin Brand Rex cables when tested in water. Although two damaged Rockbestos silicone rubber cables also failed during the accident test, no correlation between failures and level of damage was apparent

  16. Quantification of Damage Progression in a Thermally Aged Duplex Stainless Steel

    Directory of Open Access Journals (Sweden)

    A. Hazarabedian

    2002-06-01

    Full Text Available Ferrite of austeno-ferritic stainless steels maintained for a long time at temperatures in the range of 270 °C to 400 °C is embrittled like the known 475 °C embrittlement of ferritic stainless steels. Deformation and damage micromechanisms of a material must be known in order to apply the "local approach to fracture" (LAF methodology. In this work we test a previous model of damage nucleation and evolution, extending its validity to low temperature - long term aging. We have determined cracking damage evolution by taking replicas of planar tensile specimens during uniaxial traction tests. Voronoï (Dirichlet tessellation quantitative metallography was applied to characterize and quantify non-uniform damaging. Clustering criteria allowed the determination of the size, density and internal damaging rate of damage clusters.

  17. Association between age and repair of oxidatively damaged DNA in human peripheral blood mononuclear cells

    DEFF Research Database (Denmark)

    Løhr, Mille; Jensen, Annie; Eriksen, Louise;

    2015-01-01

    damaged DNA in peripheral blood mononuclear cells (PBMCs). We isolated PBMCs from subjects aged 18-83 years, as part of a health survey of the Danish population that focussed on lifestyle factors. The level of DNA repair activity was measured as incisions on potassium bromate-damaged DNA by the comet...... assay. There was an inverse association between age and DNA repair activity with a 0.65% decline in activity per year from age 18 to 83 (95% confidence interval: 0.16-1.14% per year). Univariate regression analysis also indicated inverse associations between DNA repair activity and waist-hip ratio (P...

  18. Predicting asthma exacerbations employing remotely monitored adherence.

    Science.gov (United States)

    Killane, Isabelle; Sulaiman, Imran; MacHale, Elaine; Breathnach, Aoife; Taylor, Terence E; Holmes, Martin S; Reilly, Richard B; Costello, Richard W

    2016-03-01

    This Letter investigated the efficacy of a decision-support system, designed for respiratory medicine, at predicting asthma exacerbations in a multi-site longitudinal randomised control trial. Adherence to inhaler medication was acquired over 3 months from patients with asthma employing a dose counter and a remote monitoring adherence device which recorded participant's inhaler use: n = 184 (23,656 audio files), 61% women, age (mean ± sd) 49.3 ± 16.4. Data on occurrence of exacerbations was collected at three clinical visits, 1 month apart. The relative risk of an asthma exacerbation for those with good and poor adherence was examined employing a univariate and multivariate modified Poisson regression approach; adjusting for age, gender and body mass index. For all months dose counter adherence was significantly (p research should focus on refining adherence and exacerbation measures. Decision-support systems based on remote monitoring may enhance patient-physician communication, possibly reducing preventable adverse events. PMID:27222733

  19. Exacerbations in cystic fibrosis: 2 · Prevention

    OpenAIRE

    Bell, Scott C; Robinson, Philip J

    2007-01-01

    The life span of people with cystic fibrosis (CF) has increased dramatically over the past 50 years. Many factors have contributed to this improvement. Respiratory exacerbations of CF lung disease are associated with the need for hospitalisation and antibiotic treatment, reduction in the quality of life, fragmented sleep and mortality. A number of preventive treatment strategies have been developed to reduce the frequency and severity of respiratory exacerbations in CF including mucolytic age...

  20. The Effects of Bronchiectasis on Asthma Exacerbation

    OpenAIRE

    Kang, Hye Ran; Choi, Gyu-Sik; Park, Sun Jin; Song, Yoon Kyung; Kim, Jeong Min; Ha, Junghoon; Lee, Yung Hee; Lee, Byoung Hoon; Kim, Sang-Hoon; Lee, Jae Hyung

    2014-01-01

    Background Bronchiectasis and asthma are different in many respects, but some patients have both conditions. Studies assessing the effect of bronchiectasis on asthma exacerbation are rare. The aim of this study is to investigate the effect of bronchiectasis on asthma exacerbation. Methods We enrolled 2,270 asthma patients who were followed up in our hospital. Fifty patients had bronchiectasis and asthma. We selected fifty age- and sex-matched controls from the 2,220 asthma patients without br...

  1. Prolonged Pulmonary Exposure to Diesel Exhaust Particles Exacerbates Renal Oxidative Stress, Inflammation and DNA Damage in Mice with Adenine-Induced Chronic Renal Failure

    Directory of Open Access Journals (Sweden)

    Abderrahim Nemmar

    2016-05-01

    Full Text Available Background/Aims: Epidemiological evidence indicates that patients with chronic kidney diseases have increased susceptibility to adverse outcomes related to long-term exposure to particulate air pollution. However, mechanisms underlying these effects are not fully understood. Methods: Presently, we assessed the effect of prolonged exposure to diesel exhaust particles (DEP on chronic renal failure induced by adenine (0.25% w/w in feed for 4 weeks, which is known to involve inflammation and oxidative stress. DEP (0.5m/kg was intratracheally (i.t. instilled every 4th day for 4 weeks (7 i.t. instillation. Four days following the last exposure to either DEP or saline (control, various renal endpoints were measured. Results: While body weight was decreased, kidney weight increased in DEP+adenine versus saline+adenine or DEP. Water intake, urine volume, relative kidney weight were significantly increased in adenine+DEP versus DEP and adenine+saline versus saline. Plasma creatinine and urea increased and creatinine clearance decreased in adenine+DEP versus DEP and adenine+saline versus saline. Tumor necrosis factor α, lipid peroxidation and reactive oxygen species were significantly increased in adenine+DEP compared with either DEP or adenine+saline. The antioxidant calase was significantly decreased in adenine+DEP compared with either adenine+saline or DEP. Notably, renal DNA damage was significantly potentiated in adenine+DEP compared with either adenine+saline or DEP. Similarly, systolic blood pressure was increased in adenine+DEP versus adenine+saline or DEP, and in DEP versus saline. Histological evaluation revealed more collagen deposition, higher number of necrotic cell counts and dilated tubules, cast formation and collapsing glomeruli in adenine+DEP versus adenine+saline or DEP. Conclusion: Prolonged pulmonary exposure to diesel exhaust particles worsen renal oxidative stress, inflammation and DNA damage in mice with adenine-induced chronic

  2. Cytometric Assessment of DNA Damage by Exogenous and Endogenous Oxidants Reports Aging-related Processes

    OpenAIRE

    Zhao, Hong; Tanaka, Toshiki; Halicka, H. Dorota; Traganos, Frank; Zarebski, Miroslaw; Dobrucki, Jurek; Darzynkiewicz, Zbigniew

    2007-01-01

    The ongoing DNA damage caused by reactive oxygen species generated during oxidative metabolism is considered a key factor contributing to cell aging as well as preconditioning cells to neoplastic transformation. We postulated before that a significant fraction of constitutive histone H2AX phosphorylation (CHP) and constitutive activation of ATM (CAA) seen in untreated normal and tumor cells occurs in response to such DNA damage. In the present study, we provide further evidence in support of ...

  3. Visceral adipose tissue inflammation is associated with age-related brain changes and ischemic brain damage in aged mice.

    Science.gov (United States)

    Shin, Jin A; Jeong, Sae Im; Kim, Minsuk; Yoon, Joo Chun; Kim, Hee-Sun; Park, Eun-Mi

    2015-11-01

    Visceral adipose tissue is accumulated with aging. An increase in visceral fat accompanied by low-grade inflammation is associated with several adult-onset diseases. However, the effects of visceral adipose tissue inflammation on the normal and ischemic brains of aged are not clearly defined. To examine the role of visceral adipose tissue inflammation, we evaluated inflammatory cytokines in the serum, visceral adipose tissue, and brain as well as blood-brain barrier (BBB) permeability in aged male mice (20 months) underwent sham or visceral fat removal surgery compared with the young mice (2.5 months). Additionally, ischemic brain injury was compared in young and aged mice with sham and visceral fat removal surgery. Interleukin (IL)-1β, IL-6, and tumor necrosis factor-α levels in examined organs were increased in aged mice compared with the young mice, and these levels were reduced in the mice with visceral fat removal. Increased BBB permeability with reduced expression of tight junction proteins in aged sham mice were also decreased in mice with visceral fat removal. After focal ischemic injury, aged mice with visceral fat removal showed a reduction in infarct volumes, BBB permeability, and levels of proinflammatory cytokines in the ischemic brain compared with sham mice, although the neurological outcomes were not significantly improved. In addition, further upregulated visceral adipose tissue inflammation in response to ischemic brain injury was attenuated in mice with visceral fat removal. These results suggest that visceral adipose tissue inflammation is associated with age-related changes in the brain and contributes to the ischemic brain damage in the aged mice. We suggest that visceral adiposity should be considered as a factor affecting brain health and ischemic brain damage in the aged population. PMID:26184082

  4. Mitochondrial and Nuclear DNA Damage and Repair in Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Janusz Blasiak

    2013-01-01

    Full Text Available Aging and oxidative stress seem to be the most important factors in the pathogenesis of age-related macular degeneration (AMD, a condition affecting many elderly people in the developed world. However, aging is associated with the accumulation of oxidative damage in many biomolecules, including DNA. Furthermore, mitochondria may be especially important in this process because the reactive oxygen species produced in their electron transport chain can damage cellular components. Therefore, the cellular response to DNA damage, expressed mainly through DNA repair, may play an important role in AMD etiology. In several studies the increase in mitochondrial DNA (mtDNA damage and mutations, and the decrease in the efficacy of DNA repair have been correlated with the occurrence and the stage of AMD. It has also been shown that mitochondrial DNA accumulates more DNA lesions than nuclear DNA in AMD. However, the DNA damage response in mitochondria is executed by nucleus-encoded proteins, and thus mutagenesis in nuclear DNA (nDNA may affect the ability to respond to mutagenesis in its mitochondrial counterpart. We reported that lymphocytes from AMD patients displayed a higher amount of total endogenous basal and oxidative DNA damage, exhibited a higher sensitivity to hydrogen peroxide and UV radiation, and repaired the lesions induced by these factors less effectively than did cells from control individuals. We postulate that poor efficacy of DNA repair (i.e., is impaired above average for a particular age when combined with the enhanced sensitivity of retinal pigment epithelium cells to environmental stress factors, contributes to the pathogenesis of AMD. Collectively, these data suggest that the cellular response to both mitochondrial and nuclear DNA damage may play an important role in AMD pathogenesis.

  5. Differences in cracking resistance of asphalt mixtures due to ageing and moisture damage

    OpenAIRE

    López Montero, Teresa; Miró Recasens, José Rodrigo

    2016-01-01

    The ageing phenomenon and moisture damage become key factors to evaluate mixture cracking resistance. In this paper, the effect of ageing and water on cracking resistance and fatigue behavior in a bituminous mixture is studied. Specimens were tested by a direct tensile test (Fénix test) to obtain fracture energy values whereas variation of complex modulus and dissipated energy density was obtained by a strain sweep fatigue test (EBADE test). Results show a significant reduction in cracking re...

  6. A model for damage load and its implications for the evolution of bacterial aging.

    Directory of Open Access Journals (Sweden)

    Lin Chao

    2010-08-01

    Full Text Available Deleterious mutations appearing in a population increase in frequency until stopped by natural selection. The ensuing equilibrium creates a stable frequency of deleterious mutations or the mutational load. Here I develop the comparable concept of a damage load, which is caused by harmful non-heritable changes to the phenotype. A damage load also ensues when the increase of damage is opposed by selection. The presence of a damage load favors the evolution of asymmetrical transmission of damage by a mother to her daughters. The asymmetry is beneficial because it increases fitness variance, but it also leads to aging or senescence. A mathematical model based on microbes reveals that a cell lineage dividing symmetrically is immortal if lifetime damage rates do not exceed a threshold. The evolution of asymmetry allows the lineage to persist above the threshold, but the lineage becomes mortal. In microbes with low genomic mutation rates, it is likely that the damage load is much greater than the mutational load. In metazoans with higher genomic mutation rates, the damage and the mutational load could be of the same magnitude. A fit of the model to experimental data shows that Escherichia coli cells experience a damage rate that is below the threshold and are immortal under the conditions examined. The model estimates the asymmetry level of E. coli to be low but sufficient for persisting at higher damage rates. The model also predicts that increasing asymmetry results in diminishing fitness returns, which may explain why the bacterium has not evolved higher asymmetry.

  7. Age and metabolic risk factors associated with oxidatively damaged DNA in human peripheral blood mononuclear cells

    DEFF Research Database (Denmark)

    Løhr, Mille; Jensen, Annie; Eriksen, Louise;

    2015-01-01

    18-93 years. DNA damage was analyzed as strand breaks by the comet assay and levels of formamidopyrimidine (FPG-) and human 8-oxoguanine DNA glycosylase 1 (hOGG1)-sensitive sites There was an association between age and levels of FPG-sensitive sites for women, but not for men. The same tendency was...

  8. Base excision repair of oxidative DNA damage and association with cancer and aging

    DEFF Research Database (Denmark)

    Maynard, Scott; Schurman, Shepherd H; Harboe, Charlotte;

    2009-01-01

    Aging has been associated with damage accumulation in the genome and with increased cancer incidence. Reactive oxygen species (ROS) are produced from endogenous sources, most notably the oxidative metabolism in the mitochondria, and from exogenous sources, such as ionizing radiation. ROS attack D...

  9. Antioxidants in the Canine Model of Human Aging

    OpenAIRE

    Dowling, Amy L. S.; Head, Elizabeth

    2011-01-01

    Oxidative damage can lead to neuronal dysfunction in the brain due to modifications to proteins, lipids and DNA/RNA. In both human and canine brain, oxidative damage progressively increases with age. In the Alzheimer’s disease (AD) brain, oxidative damage is further exacerbated, possibly due to increased deposition of beta-amyloid (Aβ) peptide in senile plaques. These observations have led to the hypothesis that antioxidants may be beneficial for brain aging and AD. Aged dogs naturally develo...

  10. Investigation of thermal aging damage mechanism of the Cast Duplex Stainless Steel

    Energy Technology Data Exchange (ETDEWEB)

    Wang Zhaoxi, E-mail: wangzx03@mails.tsinghua.edu.c [Applied Mechanics Laboratory, Tsinghua University, Beijing 100084 (China); Suzhou Nuclear Power Research Institute, Suzhou 215004 (China); Xue Fei; Guo Wenhai [Suzhou Nuclear Power Research Institute, Suzhou 215004 (China); Shi Huiji [Applied Mechanics Laboratory, Tsinghua University, Beijing 100084 (China); Zhang Guodong [Suzhou Nuclear Power Research Institute, Suzhou 215004 (China); School of Mechanical and Power Engineering, Nanjing University of Technology, Nanjing 210009 (China); Shu Guogang [Suzhou Nuclear Power Research Institute, Suzhou 215004 (China)

    2010-10-15

    Besides the macro-mechanical properties for thermal aging effect published in 'Thermal aging effect on Z3CN20.09M Cast Duplex Stainless Steel' (Nuclear Engineering and Design 239(2009) 2217-2223), the thermal aging damage mechanism is investigated in this paper through nano-indentation tests and micro-structures evolution examination. Numerical simulations were carried out with GTN continuum damage model to investigate the different crack propagation process for aging. The nano-indentation hardness values increase with aging time for both phases while the hardness values of the ferrite phase are much higher and increase much more. The nano-indentation energy indicating the toughness decreases for both phases with aging time. TEM results show that the Cr-enriched {alpha}' phase precipitates in the ferrite phase which is considered as the critical reason making the dislocation slip difficult and causing the increase of the strength and reduction of the toughness. The crack initiates from the ferrite phase instead of the austenite phase from the SEM observation and FEA simulation results, which reflects the change of the fracture mechanism for thermal aging.

  11. Increased mammogram-induced DNA damage in mammary epithelial cells aged in vitro.

    Directory of Open Access Journals (Sweden)

    Laia Hernández

    Full Text Available Concerned about the risks of mammography screening in the adult population, we analyzed the ability of human mammary epithelial cells to cope with mammogram-induced DNA damage. Our study shows that an X-ray dose of 20 mGy, which is the standard dose received by the breast surface per two-view mammogram X-ray exploration, induces increased frequencies of DNA double-strand breaks to in vitro aged-but not to young-human mammary epithelial cells. We provide evidence that aged epithelial breast cells are more radiosensitive than younger ones. Our studies point to an inefficient damage response of aged cells to low-dose radiation, this being due to both delayed and incomplete mobilization of repair proteins to DNA strand breaks. This inefficient damage response is translated into an important delay in double-strand break disappearance and consequent accumulation of unrepaired DNA breaks. The result of this is a significant increase in micronuclei frequency in the in vitro aged mammary epithelial cells exposed to doses equivalent to a single mammogram X-ray exploration. Since our experiments were carried out in primary epithelial cell cultures in which cells age at the same time as they undergo replication-dependent telomere shortening, we needed to determine the contribution of these two factors to their phenotype. In this paper, we report that the exogenous expression of human telomerase retrotranscriptase in late population doubling epithelial cells does not rescue its delayed repair phenotype. Therefore, retarded DNA break repair is a direct consequence of cellular aging itself, rather than a consequence of the presence of dysfunctional telomeres. Our findings of long-lasting double strand breaks and incomplete DNA break repair in the in vitro aged epithelial cells are in line with the increased carcinogenic risks of radiation exposures at older ages revealed by epidemiologic studies.

  12. Quantification of Damage Progression in a Thermally Aged Duplex Stainless Steel

    OpenAIRE

    Hazarabedian A.; Marini B.

    2002-01-01

    Ferrite of austeno-ferritic stainless steels maintained for a long time at temperatures in the range of 270 °C to 400 °C is embrittled like the known 475 °C embrittlement of ferritic stainless steels. Deformation and damage micromechanisms of a material must be known in order to apply the "local approach to fracture" (LAF) methodology. In this work we test a previous model of damage nucleation and evolution, extending its validity to low temperature - long term aging. We have determined crack...

  13. Ultraviolet Radiation, Aging and the Skin: Prevention of Damage by Topical cAMP Manipulation

    Directory of Open Access Journals (Sweden)

    Alexandra Amaro-Ortiz

    2014-05-01

    Full Text Available Being the largest and most visible organ of the body and heavily influenced by environmental factors, skin is ideal to study the long-term effects of aging. Throughout our lifetime, we accumulate damage generated by UV radiation. UV causes inflammation, immune changes, physical changes, impaired wound healing and DNA damage that promotes cellular senescence and carcinogenesis. Melanoma is the deadliest form of skin cancer and among the malignancies of highest increasing incidence over the last several decades. Melanoma incidence is directly related to age, with highest rates in individuals over the age of 55 years, making it a clear age-related disease. In this review, we will focus on UV-induced carcinogenesis and photo aging along with natural protective mechanisms that reduce amount of “realized” solar radiation dose and UV-induced injury. We will focus on the theoretical use of forskolin, a plant-derived pharmacologically active compound to protect the skin against UV injury and prevent aging symptoms by up-regulating melanin production. We will discuss its use as a topically-applied root-derived formulation of the Plectranthus barbatus (Coleus forskolii plant that grows naturally in Asia and that has long been used in various Aryuvedic teas and therapeutic preparations.

  14. Dark chocolate exacerbates acne.

    Science.gov (United States)

    Vongraviopap, Saivaree; Asawanonda, Pravit

    2016-05-01

    The effects of chocolate on acne exacerbations have recently been reevaluated. For so many years, it was thought that it had no role in worsening acne. To investigate whether 99% dark chocolate, when consumed in regular daily amounts, would cause acne to worsen in acne-prone male subjects, twenty-five acne prone male subjects were asked to consume 25 g of 99% dark chocolate daily for 4 weeks. Assessments which included Leeds revised acne scores as well as lesion counts took place weekly. Food frequency questionnaire was used, and daily activities were recorded. Statistically significant changes of acne scores and numbers of comedones and inflammatory papules were detected as early as 2 weeks into the study. At 4 weeks, the changes remained statistically significant compared to baseline. Dark chocolate when consumed in normal amounts for 4 weeks can exacerbate acne in male subjects with acne-prone skin. PMID:26711092

  15. Accelerated Aging Experiments for Prognostics of Damage Growth in Composite Materials

    Science.gov (United States)

    Saxena, Abhinav; Goebel, Kai Frank; Larrosa, Cecilia C.; Janapati, Vishnuvardhan; Roy, Surajit; Chang, Fu-Kuo

    2011-01-01

    Composite structures are gaining importance for use in the aerospace industry. Compared to metallic structures their behavior is less well understood. This lack of understanding may pose constraints on their use. One possible way to deal with some of the risks associated with potential failure is to perform in-situ monitoring to detect precursors of failures. Prognostic algorithms can be used to predict impending failures. They require large amounts of training data to build and tune damage model for making useful predictions. One of the key aspects is to get confirmatory feedback from data as damage progresses. These kinds of data are rarely available from actual systems. The next possible resource to collect such data is an accelerated aging platform. To that end this paper describes a fatigue cycling experiment with the goal to stress carbon-carbon composite coupons with various layups. Piezoelectric disc sensors were used to periodically interrogate the system. Analysis showed distinct differences in the signatures of growing failures between data collected at conditions. Periodic X-radiographs were taken to assess the damage ground truth. Results after signal processing showed clear trends of damage growth that were correlated to damage assessed from the X-ray images.

  16. Loss of Renal Tubular PGC-1α Exacerbates Diet-Induced Renal Steatosis and Age-Related Urinary Sodium Excretion in Mice.

    Science.gov (United States)

    Svensson, Kristoffer; Schnyder, Svenia; Cardel, Bettina; Handschin, Christoph

    2016-01-01

    The kidney has a high energy demand and is dependent on oxidative metabolism for ATP production. Accordingly, the kidney is rich in mitochondria, and mitochondrial dysfunction is a common denominator for several renal diseases. While the mitochondrial master regulator peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is highly expressed in kidney, its role in renal physiology is so far unclear. Here we show that PGC-1α is a transcriptional regulator of mitochondrial metabolic pathways in the kidney. Moreover, we demonstrate that mice with an inducible nephron-specific inactivation of PGC-1α in the kidney display elevated urinary sodium excretion, exacerbated renal steatosis during metabolic stress but normal blood pressure regulation. Overall, PGC-1α seems largely dispensable for basal renal physiology. However, the role of PGC-1α in renal mitochondrial biogenesis indicates that activation of PGC-1α in the context of renal disorders could be a valid therapeutic strategy to ameliorate renal mitochondrial dysfunction. PMID:27463191

  17. The effects of proliferation and DNA damage on hematopoietic stem cell function determine aging.

    Science.gov (United States)

    Khurana, Satish

    2016-07-01

    In most of the mammalian tissues, homeostasis as well as injury repair depend upon a small number of resident adult stem cells. The decline in tissue/organ function in aged organisms has been directly linked with poorly functioning stem cells. Altered function of hematopoietic stem cells (HSCs) is at the center of an aging hematopoietic system, a tissue with high cellular turnover. Poorly engrafting, myeloid-biased HSCs with higher levels of DNA damage accumulation are the hallmark features of an aged hematopoietic system. These cells show a higher proliferation rate than their younger counterparts. It was proposed that quiescence of these cells over long period of time leads to accumulation of DNA damage, eventually resulting in poor function/pathological conditions in hematopoietic system. However, various mouse models with premature aging phenotype also show highly proliferative HSCs. This review examines the evidence that links proliferation of HSCs with aging, which leads to functional changes in the hematopoietic system. Developmental Dynamics 245:739-750, 2016. © 2016 Wiley Periodicals, Inc. PMID:26813236

  18. COPD exacerbations · 3: Pathophysiology

    OpenAIRE

    O'Donnell, D. E.; Parker, C M

    2006-01-01

    Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with increased morbidity and mortality. The effective management of COPD exacerbations awaits a better understanding of the underlying pathophysiological mechanisms that shape its clinical expression. The clinical presentation of exacerbations of COPD is highly variable and ranges from episodic symptomatic deterioration that is poorly responsive to usual treatment, to devastating life threatening events. This undersc...

  19. Chronic obstructive pulmonary disease exacerbation frequency and severity

    Directory of Open Access Journals (Sweden)

    Stafyla E

    2013-11-01

    Full Text Available Eirini Stafyla, Theodora Kerenidi, Konstantinos I Gourgoulianis Respiratory Medicine Department, University of Thessaly Medical School, University Hospital of Larissa, Larissa, GreeceWe read with great interest the original work by Motegi et al1 comparing three multidimensional assessment systems – BODE (body mass index, obstruction, dyspnea, and exercise capacity index, DOSE (dyspnea, obstruction, smoking, exacerbations index and ADO (age, dyspnea, obstruction index – for predicting COPD (chronic obstructive pulmonary disease exacerbations. In this study, exacerbation rates for the first and second year were 0.57 and 0.48 per patient-year respectively, while previous exacerbations, DOSE index, FEV1% (% forced expiratory volume in 1 second predicted and long-term oxygen therapy (LTOT use were shown to be predictors of COPD exacerbations. However, this study seems to have quite different results from our own study that focused on exacerbation frequency and severity.View original paper by Motegi and colleagues.

  20. DNA damage-induced metaphase I arrest is mediated by the spindle assembly checkpoint and maternal age.

    Science.gov (United States)

    Marangos, Petros; Stevense, Michelle; Niaka, Konstantina; Lagoudaki, Michaela; Nabti, Ibtissem; Jessberger, Rolf; Carroll, John

    2015-01-01

    In mammalian oocytes DNA damage can cause chromosomal abnormalities that potentially lead to infertility and developmental disorders. However, there is little known about the response of oocytes to DNA damage. Here we find that oocytes with DNA damage arrest at metaphase of the first meiosis (MI). The MI arrest is induced by the spindle assembly checkpoint (SAC) because inhibiting the SAC overrides the DNA damage-induced MI arrest. Furthermore, this MI checkpoint is compromised in oocytes from aged mice. These data lead us to propose that the SAC is a major gatekeeper preventing the progression of oocytes harbouring DNA damage. The SAC therefore acts to integrate protection against both aneuploidy and DNA damage by preventing production of abnormal mature oocytes and subsequent embryos. Finally, we suggest escaping this DNA damage checkpoint in maternal ageing may be one of the causes of increased chromosome anomalies in oocytes and embryos from older mothers. PMID:26522734

  1. How do COPD patients respond to exacerbations?

    Directory of Open Access Journals (Sweden)

    Verheij Theo JM

    2011-08-01

    Full Text Available Abstract Background Although timely treatment of COPD exacerbations seems clinically important, nearly half of these exacerbations remain unreported and subsequently untreated. Recent studies have investigated incidence and impact of failure to seek medical treatment during exacerbations. Yet, little is known about type and timing of other self-management actions in periods of symptom deterioration. The current prospective study aims at determining the relative incidence, timing and determinants of three types of patient responses. Methods In a multicentre observational study, 121 patients (age 67 ± 11 years, FEV1pred. 48 ± 19 were followed for 6 weeks by daily diary symptom recording. Three types of action were assessed daily: planning periods of rest, breathing techniques and/or sputum clearing (type-A, increased bronchodilator use (type-B and contacting a healthcare provider (type-C. Results Type-A action was taken in 70.7%, type-B in 62.7% and type C in 17.3% of exacerbations (n = 75. Smokers were less likely to take type-A and B actions. Type-C actions were associated with more severe airflow limitation and increased number of hospital admissions in the last year. Conclusions Our study shows that most patients are willing to take timely self-management actions during exacerbations. Future research is needed to determine whether the low incidence of contacting a healthcare provider is due to a lack of self-management or healthcare accessibility.

  2. Do females behave differently in COPD exacerbation?

    Directory of Open Access Journals (Sweden)

    Kilic H

    2015-04-01

    Full Text Available Hatice Kilic,1 Nurdan Kokturk,2 Gulcin Sari,3 Mustafa Cakir41Department of Pulmonary Medicine, Ankara Atatürk Training and Research Hospital, 2Department of Pulmonary Medicine, School of Medicine, Gazi University School of Medicine, 3Department of Pulmonary Medicine, Dr. Nafiz Körez Sincan Devlet Hastanesi, 4Department of Public Health, School of Medicine, Gazi University, Ankara, TurkeyIntroduction: Little is known about whether there is any sex effect on chronic obstructive lung disease (COPD exacerbations. This study is intended to describe the possible sex-associated differences in exacerbation profile in COPD patients.Methods: A total of 384 COPD patients who were hospitalized due to exacerbation were evaluated retrospectively for their demographics and previous and current exacerbation characteristics.Results: The study was conducted on 109 (28% female patients and 275 (72% male patients. The mean age was 68.30±10.46 years. Although females had better forced expiratory volume in 1 second and near-normal forced vital capacity, they had much impaired arterial blood gas levels (partial oxygen pressure [PO2] was 36.28 mmHg vs 57.93 mmHg; partial carbon dioxide pressure [PCO2] was 45.97 mmHg vs 42.49 mmHg; P=0.001, indicating severe exacerbation with respiratory failure. More females had two exacerbations and two hospitalizations, while more men had one exacerbation and one hospitalization. Low adherence to treatment and pulmonary embolism were more frequent in females. Females had longer time from the onset of symptoms till the admission and longer hospitalization duration than males. Comorbidities were less in number and different in women (P<0.05. Women were undertreated and using more oral corticosteroids.Conclusion: Current data showed that female COPD patients might be more prone to have severe exacerbations, a higher number of hospitalizations, and prolonged length of stay for hospitalization. They have a different comorbidity

  3. Acute exacerbation of airspace enlargement with fibrosis

    Directory of Open Access Journals (Sweden)

    Tomoyuki Kakugawa

    2014-01-01

    Full Text Available In 2008, Kawabata et al. described a lesion which they termed “airspace enlargement with fibrosis” that could be included on the spectrum of smoking-related interstitial lung diseases. This group also reported that patients with airspace enlargement with fibrosis but without coexisting interstitial pneumonia of another type had no acute exacerbations and favorable prognoses on clinical follow-up. Here we describe the first case, to our knowledge, of acute exacerbation of airspace enlargement with fibrosis without coexisting interstitial pneumonia of another type. An 82-year-old man was referred to our department for worsening dyspnea and new alveolar opacities on chest radiograph following left pulmonary segmentectomy (S6 for cancer. A diagnosis of acute exacerbation of airspace enlargement with fibrosis without coexisting interstitial pneumonia of other types was made, based on pathological evidence of airspace enlargement with fibrosis and organizing diffuse alveolar damage. Treatment with high-dose methylprednisolone followed by tapered oral prednisolone resulted in gradual improvement of the clinical condition and chest radiographic findings. Clinicians should be aware that patients with airspace enlargement with fibrosis may experience acute exacerbation.

  4. Activation-induced and damage-induced cell death in aging human T cells.

    Science.gov (United States)

    Sikora, Ewa

    2015-11-01

    In multicellular organisms the proper system functionality is ensured by the balance between cell division, differentiation, senescence and death. This balance is changed during aging. Immunosenescence plays a crucial role in aging and leads to the shrinkage of T cell repertoire and the propensity to apoptosis. The elimination of expanded T cells at the end of immune response is crucial to maintain homeostasis and avoid any uncontrolled inflammation. Resting mature T lymphocytes, when activated via their antigen-specific receptor (TCR) and CD28 co-receptor, start to proliferate and then undergo the so called activation induced cell death (AICD), which mechanistically is triggered by the death receptor and leads to apoptosis. T lymphocytes, like other cells, are also exposed to damage, which can trigger the so called damage-induced cell death (DICD). It was hypothesized that oxidative stress and chronic antigenic load increasing with age reduced lymphocyte susceptibility to DICD and enhanced a proinflamatory status leading to increased AICD. However, data collected so far are inconsistent and does not support this assumption. Systematic and comprehensive studies are still needed for conclusive elucidation of the role of AICD and DICD in human immunosenescence, including the role of autophagy and necroptosis in the processes. PMID:25843236

  5. Age-dependent oxidative stress-induced DNA damage in Down's lymphocytes

    International Nuclear Information System (INIS)

    The aim of the present study was to investigate the oxidative status of lymphocytes from children (n = 7) and adults (n = 18) with Down's syndrome (DS). The basal oxidative condition, the vulnerability to in vitro hydrogen peroxide exposure, and the repair capacity were measured by means of the damage-specific alkaline comet assay. Significantly and age-independently elevated numbers of single strand breaks and oxidized bases (pyrimidines and purines) were found in the nuclear DNA of the lymphocytes in the DS group in the basal condition. These results may support the role of an increased level of endogenous oxidative stress in DS and are similar to those previously demonstrated in Alzheimer's disease. In the in vitro oxidative stress-induced state, a markedly higher extent of DNA damage was observed in DS children as compared with age- and gender-matched healthy controls, suggesting that young trisomic lymphocytes are more sensitive to oxidative stress than normal ones. However, the repair ability itself was not found to be deteriorated in either DS children or DS adults

  6. Is Physical Activity Able to Modify Oxidative Damage in Cardiovascular Aging?

    Directory of Open Access Journals (Sweden)

    Graziamaria Corbi

    2012-01-01

    Full Text Available Aging is a multifactorial process resulting in damage of molecules, cells, and tissues. It has been demonstrated that the expression and activity of antioxidant systems (SOD, HSPs are modified in aging, with reduced cell ability to counteract the oxidant molecules, and consequent weak resistance to ROS accumulation. An important mechanism involved is represented by sirtuins, the activity of which is reduced by aging. Physical activity increases the expression and the activity of antioxidant enzymes, with consequent reduction of ROS. Positive effects of physical exercise in terms of antioxidant activity could be ascribable to a greater expression and activity of SOD enzymes, HSPs and SIRT1 activity. The antioxidant effects could increase, decrease, or not change in relation to the exercise protocol. Therefore, some authors by using a new approach based on the in vivo/vitro technique demonstrated that the highest survival and proliferation and the lowest senescence were obtained by performing an aerobic training. Therefore, the in vivo/vitro technique described could represent a good tool to better understand how the exercise training mediates its effects on aging-related diseases, as elderly with heart failure that represents a special population in which the exercise plays an important role in the improvement of cardiovascular function, quality of life, and survival.

  7. Ageing-induced changes in the redox status of peripheral motor nerves imply an effect on redox signalling rather than oxidative damage

    Science.gov (United States)

    McDonagh, Brian; Scullion, Siobhan M.; Vasilaki, Aphrodite; Pollock, Natalie; McArdle, Anne; Jackson, Malcolm J.

    2016-01-01

    Ageing is associated with loss of skeletal muscle fibres, atrophy of the remaining fibres and weakness. These changes in muscle are accompanied by disruption of motor neurons and neuromuscular junctions although the direct relationship between the nerve and muscle degeneration is not understood. Oxidative changes have been implicated in the mechanisms leading to age-related loss of muscle mass and in degeneration of the central nervous system, but little is known about age-related changes in oxidation in specific peripheral nerves that supply muscles that are affected by ageing. We have therefore examined the sciatic nerve of old mice at an age when loss of tibialis anterior muscle mass and function is apparent. Sciatic nerve from old mice did not show a gross increase in oxidative damage, but electron paramagnetic resonance (EPR) studies indicated an increase in the activity of superoxide and/or peroxynitrite in the nerves of old mice at rest that was further exacerbated by electrical stimulation of the nerve to activate muscle contractions. Proteomic analyses indicated that specific redox-sensitive proteins are increased in content in the nerves of old mice that may reflect an adaptation to regulate the increased superoxide/peroxynitrite and maintain redox homoeostasis. Analysis of redox active cysteines showed some increase in reversible oxidation in specific proteins in nerves of old mice, but this was not universally seen across all redox-active cysteines. Detailed analysis of the redox-active cysteine in one protein in the nerve of old mice that is key to redox signalling (Peroxiredoxin 6, Cys 47) showed a minor increase in reversible oxidation that would be compatible with a change in its redox signalling function. In conclusion, the data presented indicate that sciatic nerve from old mice does not show a gross increase in oxidative damage similar to that seen in the TA and other muscles that it innervates. Our results indicate an adaptation to increased

  8. COPD exacerbations · 1: Epidemiology

    OpenAIRE

    Donaldson, G C; Wedzicha, J A

    2006-01-01

    The epidemiology of exacerbations of chronic obstructive pulmonary disease (COPD) is reviewed with particular reference to the definition, frequency, time course, natural history and seasonality, and their relationship with decline in lung function, disease severity and mortality. The importance of distinguishing between recurrent and relapsed exacerbations is discussed.

  9. Behaviour and damage of aged austenitic-ferritic steels: a micro-mechanical approach

    International Nuclear Information System (INIS)

    The austenitic-ferritic steels are used in the PWR primary cooling system. At the running temperature (320 C), they are submitted to a slow aging, which leads to the embrittlement of the ferritic phase. This embrittlement leads to a decrease of the mechanical properties, in particular of the crack resistance of the austenitic-ferritic steels. The damage and rupture of the austenitic-ferritic steels have been approached at the ENSMP by the works of P. Joly (1992) and of L. Devilliers-Guerville (1998). These works have allowed to reveal a damage heterogeneity which induces a strong dispersion on the ductilities and the toughnesses as well as on the scale effects. Modeling including the damage growth kinetics measured experimentally, have allowed to verify these effects. Nevertheless, they do not consider the two-phase character of the material and do not include a physical model of the cleavage cracks growth which appear in the embrittled ferrite. In this study, is proposed a description of the material allowing to treat these aspects while authorizing the structure calculation. In a first part, the material is studied. The use of the ESBD allows to specify the complex morphology of these steels and crystal orientation relations between the two phases. Moreover, it is shown that the two phases keep the same crystal orientation in the zones, called bicrystals, whose size varies between 500 μm and 1 mm. The study of the sliding lines, coupled to the ESBD, allows to specify too the deformation modes of the two phases. At last, tensile and tensile-compression tests at various deformation range are carried out to characterize the macroscopic mechanical behaviour of these materials. Then, a micro-mechanical modeling of the material behaviour is proposed. This one takes into account the three scales identified at the preceding chapter. The first scale, corresponding to the laths is described as a monocrystal whose behaviour includes both an isotropic and a kinematic strain

  10. Accelerated aging tests of radiation damaged lasers and photodiodes for the CMS tracker optical links

    CERN Document Server

    Gill, K; Batten, J; Cervelli, G; Grabit, R; Jensen, F; Troska, Jan K; Vasey, F

    1999-01-01

    The combined effects of radiation damage and accelerated ageing in COTS lasers and p-i-n photodiodes are presented. Large numbers of these devices are employed in future High Energy Physics experiments and it is vital that these devices are confirmed to be sufficiently robust in terms of both radiation resistance and reliability. Forty 1310 nm InGaAsP edge-emitting lasers (20 irradiated) and 30 InGaAs p- i-n photodiodes (19 irradiated) were aged for 4000 hours at 80 degrees C with periodic measurements made of laser threshold and efficiency, in addition to p-i-n leakage current and photocurrent. There were no sudden failures and there was very little wearout- related degradation in either unirradiated or irradiated sample groups. The results suggest that the tested devices have a sufficiently long lifetime to operate for at least 10 years inside the Compact Muon Solenoid experiment despite being exposed to a harsh radiation environment. (13 refs).

  11. COPD exacerbations, inflammation and treatment

    OpenAIRE

    Bathoorn, Derk

    2007-01-01

    This thesis describes investigations into the inflammation in COPD, and its treatment. Inflammation in COPD is a central factor in the onset of the disease and its progression. During acute deteriorations of the disease, exacerbations, the inflammation is more severe, and depending on the cause of the exacerbation, it has a different pattern. To date, it has been difficult to efficiently suppress this inflammation, and the anti-inflammatory treatment currently so far has considerable side eff...

  12. Job strain and the risk of severe asthma exacerbations

    DEFF Research Database (Denmark)

    Heikkilä, K; Madsen, I E H; Nyberg, S T;

    2014-01-01

    in working-age European men and women. METHODS: We analysed individual-level data, collected between 1985 and 2010, from 102 175 working-age men and women in 11 prospective European studies. Job strain (a combination of high demands and low control at work) was self-reported at baseline. Incident...... 10 years, 1 109 individuals experienced a severe asthma exacerbation (430 with asthma as the primary diagnostic code). In the age- and sex-adjusted analyses, job strain was associated with an increased risk of severe asthma exacerbations defined using the primary diagnostic code (hazard ratio, HR: 1...

  13. Ultraviolet Radiation-Induced Skin Aging: The Role of DNA Damage and Oxidative Stress in Epidermal Stem Cell Damage Mediated Skin Aging

    OpenAIRE

    Uraiwan Panich; Gunya Sittithumcharee; Natwarath Rathviboon; Siwanon Jirawatnotai

    2016-01-01

    Skin is the largest human organ. Skin continually reconstructs itself to ensure its viability, integrity, and ability to provide protection for the body. Some areas of skin are continuously exposed to a variety of environmental stressors that can inflict direct and indirect damage to skin cell DNA. Skin homeostasis is maintained by mesenchymal stem cells in inner layer dermis and epidermal stem cells (ESCs) in the outer layer epidermis. Reduction of skin stem cell number and function has been...

  14. Using autopsy brain tissue to study alcohol-related brain damage in the genomic age.

    Science.gov (United States)

    Sutherland, Greg T; Sheedy, Donna; Kril, Jillian J

    2014-01-01

    The New South Wales Tissue Resource Centre at the University of Sydney, Australia, is one of the few human brain banks dedicated to the study of the effects of chronic alcoholism. The bank was affiliated in 1994 as a member of the National Network of Brain Banks and also focuses on schizophrenia and healthy control tissue. Alcohol abuse is a major problem worldwide, manifesting in such conditions as fetal alcohol syndrome, adolescent binge drinking, alcohol dependency, and alcoholic neurodegeneration. The latter is also referred to as alcohol-related brain damage (ARBD). The study of postmortem brain tissue is ideally suited to determining the effects of long-term alcohol abuse, but it also makes an important contribution to understanding pathogenesis across the spectrum of alcohol misuse disorders and potentially other neurodegenerative diseases. Tissue from the bank has contributed to 330 peer-reviewed journal articles including 120 related to alcohol research. Using the results of these articles, this review chronicles advances in alcohol-related brain research since 2003, the so-called genomic age. In particular, it concentrates on transcriptomic approaches to the pathogenesis of ARBD and builds on earlier reviews of structural changes (Harper et al. Prog Neuropsychopharmacol Biol Psychiatry 2003;27:951) and proteomics (Matsumoto et al. Expert Rev Proteomics 2007;4:539). PMID:24033426

  15. Acute kidney injury in stable COPD and at exacerbation

    Directory of Open Access Journals (Sweden)

    Barakat MF

    2015-09-01

    Full Text Available MF Barakat,1 HI McDonald,1 TJ Collier,1 L Smeeth,1 D Nitsch,1 JK Quint1,2 1Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, 2Department of Respiratory Epidemiology, Occupational Medicine and Public Health, National Heart and Lung Institute, Imperial College London, London, UK Background: While acute kidney injury (AKI alone is associated with increased mortality, the incidence of hospital admission with AKI among stable and exacerbating COPD patients and the effect of concurrent AKI at COPD exacerbation on mortality is not known.Methods: A total of 189,561 individuals with COPD were identified from the Clinical Practice Research Datalink. Using Poisson and logistic regressions, we explored which factors predicted admission for AKI (identified in Hospital Episode Statistics in this COPD cohort and concomitant AKI at a hospitalization for COPD exacerbation. Using survival analysis, we investigated the effect of concurrent AKI at exacerbation on mortality (n=36,107 and identified confounding factors.Results: The incidence of AKI in the total COPD cohort was 128/100,000 person-years. The prevalence of concomitant AKI at exacerbation was 1.9%, and the mortality rate in patients with AKI at exacerbation was 521/1,000 person-years. Male sex, older age, and lower glomerular filtration rate predicted higher risk of AKI or death. There was a 1.80 fold (95% confidence interval: 1.61, 2.03 increase in adjusted mortality within the first 6 months post COPD exacerbation in patients suffering from AKI and COPD exacerbation compared to those who were AKI free.Conclusion: In comparison to previous studies on general populations and hospitalizations, the incidence and prevalence of AKI is relatively high in COPD patients. Coexisting AKI at exacerbation is prognostic of poor outcome. Keywords: acute renal failure, mortality, emphysema, chronic bronchitis, prognosis

  16. Damages dependent sensitivity of Zircon (U-Th)/He ages to thermal processes: the case of Pyrenean samples

    Science.gov (United States)

    Pik, Raphael; Zimmermann, Laurent; Bellahsen, Nicolas; Vacherat, Arnaud; Ternois, Sébastien; Mouthereau, Frédéric; Ford, Mary

    2016-04-01

    During the last decade (U-Th)/He thermochronology experienced important developments and improvements based on the combined use of extensive age documentation on various contexts and numerous experimental data. The main advance has been achieved when it has been shown that He diffusion in apatites is partly controlled by the amount of radiation damages accumulated in the grains. Concerning zircons, it has been noticed that Z-He ages could positively or negatively correlate with the amount of effective uranium (eU) of the grains (a parameter proportional to the accumulated damages). It has been shown that the alpha-dose is correlated to the amount of accumulated radiation damages and controls the diffusivity of helium by first inhibiting helium migration at low damage, before a threshold (2 x 1018 alpha/g), after which interconnection of damage zones drastically drives higher diffusivity at high damage (Gunethner et al., 2013). In this study we provide new Zircon Fission Track ages (ZFT) and single grain Zircon (U-Th)/He ages (Z-He) from Hercynian Pyrenean granites. The time-temperature history of exhumation for the western part of the Axial Zone in the Pyrenees is particularly well suited for such an investigation given that (1) the age of granite bodies is very well known (~ 305 Ma), and (2) they have spent a large part of their Mesozoic history close to the surface favoring accumulation of radiation damages before Paleocene sedimentary and tectonic burial 5. In general, data exhibit a wide range of ages with maximum variation mainly recorded for a narrow eU concentration window from 200 to 500 ppm, with a first steep positive gradient, and a subsequent more gentle negative one up to the youngest ages recorded for the highest eU. For individual localities, the total age variation range from published AFT dates for the lower bound to ages in good agreement with ZFT for the upper bound. Such pattern is qualitatively in pretty good agreement with the model of

  17. PGC-1α Modulates Telomere Function and DNA Damage in Protecting against Aging-Related Chronic Diseases.

    Science.gov (United States)

    Xiong, Shiqin; Patrushev, Nikolay; Forouzandeh, Farshad; Hilenski, Lula; Alexander, R Wayne

    2015-09-01

    Cellular senescence and organismal aging predispose age-related chronic diseases, such as neurodegenerative, metabolic, and cardiovascular disorders. These diseases emerge coincidently from elevated oxidative/electrophilic stress, inflammation, mitochondrial dysfunction, DNA damage, and telomere dysfunction and shortening. Mechanistic linkages are incompletely understood. Here, we show that ablation of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) accelerates vascular aging and atherosclerosis, coinciding with telomere dysfunction and shortening and DNA damage. PGC-1α deletion reduces expression and activity of telomerase reverse transcriptase (TERT) and increases p53 levels. Ectopic expression of PGC-1α coactivates TERT transcription and reverses telomere malfunction and DNA damage. Furthermore, alpha lipoic acid (ALA), a non-dispensable mitochondrial cofactor, upregulates PGC-1α-dependent TERT and the cytoprotective Nrf-2-mediated antioxidant/electrophile-responsive element (ARE/ERE) signaling cascades, and counteracts high-fat-diet-induced, age-dependent arteriopathy. These results illustrate the pivotal importance of PGC-1α in ameliorating senescence, aging, and associated chronic diseases, and may inform novel therapeutic approaches involving electrophilic specificity. PMID:26299964

  18. PGC-1α Modulates Telomere Function and DNA Damage in Protecting against Aging-Related Chronic Diseases

    Directory of Open Access Journals (Sweden)

    Shiqin Xiong

    2015-09-01

    Full Text Available Cellular senescence and organismal aging predispose age-related chronic diseases, such as neurodegenerative, metabolic, and cardiovascular disorders. These diseases emerge coincidently from elevated oxidative/electrophilic stress, inflammation, mitochondrial dysfunction, DNA damage, and telomere dysfunction and shortening. Mechanistic linkages are incompletely understood. Here, we show that ablation of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α accelerates vascular aging and atherosclerosis, coinciding with telomere dysfunction and shortening and DNA damage. PGC-1α deletion reduces expression and activity of telomerase reverse transcriptase (TERT and increases p53 levels. Ectopic expression of PGC-1α coactivates TERT transcription and reverses telomere malfunction and DNA damage. Furthermore, alpha lipoic acid (ALA, a non-dispensable mitochondrial cofactor, upregulates PGC-1α-dependent TERT and the cytoprotective Nrf-2-mediated antioxidant/electrophile-responsive element (ARE/ERE signaling cascades, and counteracts high-fat-diet-induced, age-dependent arteriopathy. These results illustrate the pivotal importance of PGC-1α in ameliorating senescence, aging, and associated chronic diseases, and may inform novel therapeutic approaches involving electrophilic specificity.

  19. Influence of Age on Brain Edema Formation, Secondary Brain Damage and Inflammatory Response after Brain Trauma in Mice

    Science.gov (United States)

    Timaru-Kast, Ralph; Luh, Clara; Gotthardt, Philipp; Huang, Changsheng; Schäfer, Michael K.; Engelhard, Kristin; Thal, Serge C.

    2012-01-01

    After traumatic brain injury (TBI) elderly patients suffer from higher mortality rate and worse functional outcome compared to young patients. However, experimental TBI research is primarily performed in young animals. Aim of the present study was to clarify whether age affects functional outcome, neuroinflammation and secondary brain damage after brain trauma in mice. Young (2 months) and old (21 months) male C57Bl6N mice were anesthetized and subjected to a controlled cortical impact injury (CCI) on the right parietal cortex. Animals of both ages were randomly assigned to 15 min, 24 h, and 72 h survival. At the end of the observation periods, contusion volume, brain water content, neurologic function, cerebral and systemic inflammation (CD3+ T cell migration, inflammatory cytokine expression in brain and lung, blood differential cell count) were determined. Old animals showed worse neurological function 72 h after CCI and a high mortality rate (19.2%) compared to young (0%). This did not correlate with histopathological damage, as contusion volumes were equal in both age groups. Although a more pronounced brain edema formation was detected in old mice 24 hours after TBI, lack of correlation between brain water content and neurological deficit indicated that brain edema formation is not solely responsible for age-dependent differences in neurological outcome. Brains of old naïve mice were about 8% smaller compared to young naïve brains, suggesting age-related brain atrophy with possible decline in plasticity. Onset of cerebral inflammation started earlier and primarily ipsilateral to damage in old mice, whereas in young mice inflammation was delayed and present in both hemispheres with a characteristic T cell migration pattern. Pulmonary interleukin 1β expression was up-regulated after cerebral injury only in young, not aged mice. The results therefore indicate that old animals are prone to functional deficits and strong ipsilateral cerebral inflammation

  20. Influence of age on brain edema formation, secondary brain damage and inflammatory response after brain trauma in mice.

    Directory of Open Access Journals (Sweden)

    Ralph Timaru-Kast

    Full Text Available After traumatic brain injury (TBI elderly patients suffer from higher mortality rate and worse functional outcome compared to young patients. However, experimental TBI research is primarily performed in young animals. Aim of the present study was to clarify whether age affects functional outcome, neuroinflammation and secondary brain damage after brain trauma in mice. Young (2 months and old (21 months male C57Bl6N mice were anesthetized and subjected to a controlled cortical impact injury (CCI on the right parietal cortex. Animals of both ages were randomly assigned to 15 min, 24 h, and 72 h survival. At the end of the observation periods, contusion volume, brain water content, neurologic function, cerebral and systemic inflammation (CD3+ T cell migration, inflammatory cytokine expression in brain and lung, blood differential cell count were determined. Old animals showed worse neurological function 72 h after CCI and a high mortality rate (19.2% compared to young (0%. This did not correlate with histopathological damage, as contusion volumes were equal in both age groups. Although a more pronounced brain edema formation was detected in old mice 24 hours after TBI, lack of correlation between brain water content and neurological deficit indicated that brain edema formation is not solely responsible for age-dependent differences in neurological outcome. Brains of old naïve mice were about 8% smaller compared to young naïve brains, suggesting age-related brain atrophy with possible decline in plasticity. Onset of cerebral inflammation started earlier and primarily ipsilateral to damage in old mice, whereas in young mice inflammation was delayed and present in both hemispheres with a characteristic T cell migration pattern. Pulmonary interleukin 1β expression was up-regulated after cerebral injury only in young, not aged mice. The results therefore indicate that old animals are prone to functional deficits and strong ipsilateral cerebral

  1. Aging.

    Science.gov (United States)

    Park, Dong Choon; Yeo, Seung Geun

    2013-09-01

    Aging is initiated based on genetic and environmental factors that operate from the time of birth of organisms. Aging induces physiological phenomena such as reduction of cell counts, deterioration of tissue proteins, tissue atrophy, a decrease of the metabolic rate, reduction of body fluids, and calcium metabolism abnormalities, with final progression onto pathological aging. Despite the efforts from many researchers, the progression and the mechanisms of aging are not clearly understood yet. Therefore, the authors would like to introduce several theories which have gained attentions among the published theories up to date; genetic program theory, wear-and-tear theory, telomere theory, endocrine theory, DNA damage hypothesis, error catastrophe theory, the rate of living theory, mitochondrial theory, and free radical theory. Although there have been many studies that have tried to prevent aging and prolong life, here we introduce a couple of theories which have been proven more or less; food, exercise, and diet restriction. PMID:24653904

  2. Differential Effect of Endurance Training on Mitochondrial Protein Damage, Degradation, and Acetylation in the Context of Aging.

    Science.gov (United States)

    Johnson, Matthew L; Irving, Brian A; Lanza, Ian R; Vendelbo, Mikkel H; Konopka, Adam R; Robinson, Matthew M; Henderson, Gregory C; Klaus, Katherine A; Morse, Dawn M; Heppelmann, Carrie; Bergen, H Robert; Dasari, Surendra; Schimke, Jill M; Jakaitis, Daniel R; Nair, K Sreekumaran

    2015-11-01

    Acute aerobic exercise increases reactive oxygen species and could potentially damage proteins, but exercise training (ET) enhances mitochondrial respiration irrespective of age. Here, we report a differential impact of ET on protein quality in young and older participants. Using mass spectrometry we measured oxidative damage to skeletal muscle proteins before and after 8 weeks of ET and find that young but not older participants reduced oxidative damage to both total skeletal muscle and mitochondrial proteins. Young participants showed higher total and mitochondrial derived semitryptic peptides and 26S proteasome activity indicating increased protein degradation. ET however, increased the activity of the endogenous antioxidants in older participants. ET also increased skeletal muscle content of the mitochondrial deacetylase SIRT3 in both groups. A reduction in the acetylation of isocitrate dehydrogenase 2 was observed following ET that may counteract the effect of acute oxidative stress. In conclusion aging is associated with an inability to improve skeletal muscle and mitochondrial protein quality in response to ET by increasing degradation of damaged proteins. ET does however increase muscle and mitochondrial antioxidant capacity in older individuals, which provides increased buffering from the acute oxidative effects of exercise. PMID:25504576

  3. Ultra-Sensitive Sequencing Reveals an Age-Related Increase in Somatic Mitochondrial Mutations That Are Inconsistent with Oxidative Damage

    OpenAIRE

    Kennedy, Scott R.; Salk, Jesse J.; Schmitt, Michael W.; Loeb, Lawrence A.

    2013-01-01

    Mitochondrial DNA (mtDNA) is believed to be highly vulnerable to age-associated damage and mutagenesis by reactive oxygen species (ROS). However, somatic mtDNA mutations have historically been difficult to study because of technical limitations in accurately quantifying rare mtDNA mutations. We have applied the highly sensitive Duplex Sequencing methodology, which can detect a single mutation among >107 wild type molecules, to sequence mtDNA purified from human brain tissue from both young an...

  4. Histamine 1 receptor knock out mice show age-dependent susceptibility to status epilepticus and consequent neuronal damage.

    Science.gov (United States)

    Kukko-Lukjanov, Tiina-Kaisa; Grönman, Maria; Lintunen, Minnamaija; Laurén, Hanna B; Michelsen, Kimmo A; Panula, Pertti; Holopainen, Irma E

    2012-06-01

    The central histaminergic neuron system is an important regulator of activity stages such as arousal and sleep. In several epilepsy models, histamine has been shown to modulate epileptic activity and histamine 1 (H1) receptors seem to play a key role in this process. However, little is known about the H1 receptor-mediated seizure regulation during the early postnatal development, and therefore we examined differences in severity of kainic acid (KA)-induced status epilepticus (SE) and consequent neuronal damage in H1 receptor knock out (KO) and wild type (WT) mice at postnatal days 14, 21, and 60 (P14, P21, and P60). Our results show that in P14 H1 receptor KO mice, SE severity and neuronal damage were comparable to those of WT mice, whereas P21 KO mice had significantly decreased survival, more severe seizures, and enhanced neuronal damage in various brain regions, which were observed only in males. In P60 mice, SE severity did not differ between the genotypes, but in KO group, neuronal damage was significantly increased. Our results suggest that H1 receptors could contribute to regulation of seizures and neuronal damage age-dependently thus making the histaminergic system as a challenging target for novel drug design in epilepsy. PMID:22348791

  5. Laser microbeams for DNA damage induction, optical tweezers for the search on blood pressure relaxing drugs: contributions to ageing research

    Science.gov (United States)

    Grigaravicius, P.; Monajembashi, S.; Hoffmann, M.; Altenberg, B.; Greulich, K. O.

    2009-08-01

    One essential cause of human ageing is the accumulation of DNA damages during lifetime. Experimental studies require quantitative induction of damages and techniques to visualize the subsequent DNA repair. A new technique, the "immuno fluorescent comet assay", is used to directly visualize DNA damages in the microscope. Using DNA repair proteins fluorescently labeled with green fluorescent protein, it could be shown that the repair of the most dangerous DNA double strand breaks starts with the inaccurate "non homologous end joining" pathway and only after 1 - 1 ½ minutes may switch to the more accurate "homologous recombination repair". One might suggest investigating whether centenarians use "homologous recombination repair" differently from those ageing at earlier years and speculate whether it is possible, for example by nutrition, to shift DNA repair to a better use of the error free pathway and thus promote healthy ageing. As a complementary technique optical tweezers, and particularly its variant "erythrocyte mediated force application", is used to simulate the effects of blood pressure on HUVEC cells representing the inner lining of human blood vessels. Stimulating one cell induces in the whole neighbourhood waves of calcium and nitric oxide, known to relax blood vessels. NIFEDIPINE and AMLODIPINE, both used as drugs in the therapy of high blood pressure, primarily a disease of the elderly, prolong the availability of nitric oxide. This partially explains their mode of action. In contrast, VERAPAMILE, also a blood pressure reducing drug, does not show this effect, indicating that obviously an alternative mechanism must be responsible for vessel relaxation.

  6. Development of creep damage assessment system for aged thermal power plant

    Energy Technology Data Exchange (ETDEWEB)

    Nonaka, Isamu [IshikawaJima-Harima Heavy Industries Co., Ltd., Tokyo (Japan); Umaki, Hideo [Ishikawajima-Harima Heavy Industries Co., Ltd., Tokyo (Japan); Nishida, Hidetalca [The Chugoku Electric Power Co., Inc., Hiroshima (Japan); Yamaguchi, Hiroshi [The Chugoku Electric Power Co., Inc., Hiroshima (Japan)

    1998-12-31

    IHI has developed the Creep Damage Assessment System to identify voids by processing an image observed by a small laser microscope with an advanced image processing technique jointly with Chugoku Electric Power Co., Inc. The result can be obtained immediately on the spot. Application tests of the system at the Unit No.3 boiler of the Kudamatsu Power Station showed good operability, adaptability to the environment, and accuracy. The new system can easily indicate damage conditions in parts during the periodical inspection, allowing rapid maintenance. Time reduction required for assessment and increased reliability of equipment can be also achieved. (orig.)

  7. Chronic obstructive pulmonary disease exacerbation frequency and severity

    OpenAIRE

    Stafyla, Eirini

    2013-01-01

    Eirini Stafyla, Theodora Kerenidi, Konstantinos I Gourgoulianis Respiratory Medicine Department, University of Thessaly Medical School, University Hospital of Larissa, Larissa, GreeceWe read with great interest the original work by Motegi et al1 comparing three multidimensional assessment systems – BODE (body mass index, obstruction, dyspnea, and exercise capacity) index, DOSE (dyspnea, obstruction, smoking, exacerbations) index and ADO (age, dyspnea, obstruction) index – ...

  8. Ultra-sensitive sequencing reveals an age-related increase in somatic mitochondrial mutations that are inconsistent with oxidative damage.

    Science.gov (United States)

    Kennedy, Scott R; Salk, Jesse J; Schmitt, Michael W; Loeb, Lawrence A

    2013-01-01

    Mitochondrial DNA (mtDNA) is believed to be highly vulnerable to age-associated damage and mutagenesis by reactive oxygen species (ROS). However, somatic mtDNA mutations have historically been difficult to study because of technical limitations in accurately quantifying rare mtDNA mutations. We have applied the highly sensitive Duplex Sequencing methodology, which can detect a single mutation among >10(7) wild type molecules, to sequence mtDNA purified from human brain tissue from both young and old individuals with unprecedented accuracy. We find that the frequency of point mutations increases ~5-fold over the course of 80 years of life. Overall, the mutation spectra of both groups are comprised predominantly of transition mutations, consistent with misincorporation by DNA polymerase γ or deamination of cytidine and adenosine as the primary mutagenic events in mtDNA. Surprisingly, G → T mutations, considered the hallmark of oxidative damage to DNA, do not significantly increase with age. We observe a non-uniform, age-independent distribution of mutations in mtDNA, with the D-loop exhibiting a significantly higher mutation frequency than the rest of the genome. The coding regions, but not the D-loop, exhibit a pronounced asymmetric accumulation of mutations between the two strands, with G → A and T → C mutations occurring more often on the light strand than the heavy strand. The patterns and biases we observe in our data closely mirror the mutational spectrum which has been reported in studies of human populations and closely related species. Overall our results argue against oxidative damage being a major driver of aging and suggest that replication errors by DNA polymerase γ and/or spontaneous base hydrolysis are responsible for the bulk of accumulating point mutations in mtDNA. PMID:24086148

  9. Studies on ageing and the severity of radiographic joint damage in rheumatoid arthritis

    NARCIS (Netherlands)

    Mangnus, Lukas; van Steenbergen, Hanna W.; Lindqvist, Elisabet; Brouwer, Elisabeth; Reijnierse, Monique; Huizinga, Tom W. J.; Gregersen, Peter K.; Berglin, Ewa; Rantapaa-Dahlqvist, Solbritt; van der Heijde, Desiree; van der Helm-van Mil, Annette H. M.

    2015-01-01

    Introduction: The western population is ageing. It is unknown whether age at diagnosis affects the severity of Rheumatoid Arthritis (RA), we therefore performed the present study. Method: 1,875 RA-patients (7,219 radiographs) included in five European and North-American cohorts (Leiden-EAC, Wichita,

  10. Polμ deficiency increases resistance to oxidative damage and delays liver aging.

    Directory of Open Access Journals (Sweden)

    Beatriz Escudero

    Full Text Available Polμ is an error-prone PolX polymerase that contributes to classical NHEJ DNA repair. Mice lacking Polμ (Polμ(-/- show altered hematopoiesis homeostasis and DSB repair and a more pronounced nucleolytic resection of some V(DJ junctions. We previously showed that Polμ(-/- mice have increased learning capacity at old ages, suggesting delayed brain aging. Here we investigated the effect of Polμ(-/- deficiency on liver aging. We found that old Polμ(-/- mice (>20 month have greater liver regenerative capacity compared with wt animals. Old Polμ(-/- liver showed reduced genomic instability and increased apoptosis resistance. However, Polμ(-/- mice did not show an extended life span and other organs (e.g., heart aged normally. Our results suggest that Polμ deficiency activates transcriptional networks that reduce constitutive apoptosis, leading to enhanced liver repair at old age.

  11. Mitochondrial Oxidative Damage in Aging and Alzheimer's Disease: Implications for Mitochondrially Targeted Antioxidant Therapeutics

    OpenAIRE

    Reddy, P. Hemachandra

    2006-01-01

    The overall aim of this article is to review current therapeutic strategies for treating AD, with a focus on mitochondrially targeted antioxidant treatments. Recent advances in molecular, cellular, and animal model studies of AD have revealed that amyloid precursor protein derivatives, including amyloid beta (Aβ) monomers and oligomers, are likely key factors in tau hyperphosphorylation, mitochondrial oxidative damage, inflammatory changes, and synaptic failure in the brain tissue of AD patie...

  12. Retinal pigment epithelial cell multinucleation in the aging eye - a mechanism to repair damage and maintain homoeostasis.

    Science.gov (United States)

    Chen, Mei; Rajapakse, Dinusha; Fraczek, Monika; Luo, Chang; Forrester, John V; Xu, Heping

    2016-06-01

    Retinal pigment epithelial (RPE) cells are central to retinal health and homoeostasis. Dysfunction or death of RPE cells underlies many age-related retinal degenerative disorders particularly age-related macular degeneration. During aging RPE cells decline in number, suggesting an age-dependent cell loss. RPE cells are considered to be postmitotic, and how they repair damage during aging remains poorly defined. We show that RPE cells increase in size and become multinucleate during aging in C57BL/6J mice. Multinucleation appeared not to be due to cell fusion, but to incomplete cell division, that is failure of cytokinesis. Interestingly, the phagocytic activity of multinucleate RPE cells was not different from that of mononuclear RPE cells. Furthermore, exposure of RPE cells in vitro to photoreceptor outer segment (POS), particularly oxidized POS, dose-dependently promoted multinucleation and suppressed cell proliferation. Both failure of cytokinesis and suppression of proliferation required contact with POS. Exposure to POS also induced reactive oxygen species and DNA oxidation in RPE cells. We propose that RPE cells have the potential to proliferate in vivo and to repair defects in the monolayer. We further propose that the conventionally accepted 'postmitotic' status of RPE cells is due to a modified form of contact inhibition mediated by POS and that RPE cells are released from this state when contact with POS is lost. This is seen in long-standing rhegmatogenous retinal detachment as overtly proliferating RPE cells (proliferative vitreoretinopathy) and more subtly as multinucleation during normal aging. Age-related oxidative stress may promote failure of cytokinesis and multinucleation in RPE cells. PMID:26875723

  13. Assessment of Accrued Damage and Remaining Useful Life in Leadfree Electronics Subjected to Multiple Thermal Environments of Thermal Aging and Thermal Cycling

    Data.gov (United States)

    National Aeronautics and Space Administration — A method has been developed for prognostication of accrued prior damage in electronics subjected to overlapping sequential environments of thermal aging and thermal...

  14. Blocking rpS6 Phosphorylation Exacerbates Tsc1 Deletion-Induced Kidney Growth.

    Science.gov (United States)

    Wu, Huijuan; Chen, Jianchun; Xu, Jinxian; Dong, Zheng; Meyuhas, Oded; Chen, Jian-Kang

    2016-04-01

    The molecular mechanisms underlying renal growth and renal growth-induced nephron damage remain poorly understood. Here, we report that in murine models, deletion of the tuberous sclerosis complex protein 1 (Tsc1) in renal proximal tubules induced strikingly enlarged kidneys, with minimal cystogenesis and occasional microscopic tumorigenesis. Signaling studies revealed hyperphosphorylation of eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) and increased phosphorylation of ribosomal protein S6 (rpS6) in activated renal tubules. Notably, knockin of a nonphosphorylatable rpS6 in theseTsc1-mutant mice exacerbated cystogenesis and caused drastic nephron damage and renal fibrosis, leading to kidney failure and a premature death rate of 67% by 9 weeks of age. In contrast,Tsc1single-mutant mice were all alive and had far fewer renal cysts at this age. Mechanistic studies revealed persistent activation of mammalian target of rapamycin complex 1 (mTORC1) signaling causing hyperphosphorylation and consequent accumulation of 4E-BP1, along with greater cell proliferation, in the renal tubules ofTsc1andrpS6double-mutant mice. Furthermore, pharmacologic treatment ofTsc1single-mutant mice with rapamycin reduced hyperphosphorylation and accumulation of 4E-BP1 but also inhibited phosphorylation of rpS6. Rapamycin also exacerbated cystic and fibrotic lesions and impaired kidney function in these mice, consequently leading to a premature death rate of 40% within 2 weeks of treatment, despite destroying tumors and decreasing kidney size. These findings indicate that Tsc1 prevents aberrant renal growth and tumorigenesis by inhibiting mTORC1 signaling, whereas phosphorylated rpS6 suppresses cystogenesis and fibrosis inTsc1-deleted kidneys. PMID:26296742

  15. Damage Assessment of Creep Tested and Thermally Aged Metallic Alloys Using Acousto-Ultrasonics

    Science.gov (United States)

    Gyekenyesi, Andrew L.; Kautz, Harold E.; Baaklini, George Y.

    2001-01-01

    In recent years emphasis has been placed on the early detection of material changes experienced in turbine powerplant components. During the scheduled overhaul of a turbine, the current techniques of examination of various hot section components aim to find flaws such as cracks, wear, and erosion, as well as excessive deformations. Thus far, these localized damage modes have been detected with satisfactory results. However, the techniques used to find these flaws provide no information on life until the flaws are actually detected. Major improvements in damage assessment, safety, as well as more accurate life prediction could be achieved if nondestructive evaluation (NDE) techniques could be utilized to sense material changes that occur prior to the localized defects mentioned. Because of elevated temperatures and excessive stresses, turbine components may experience creep behavior. As a result, it is desirable to monitor and access the current condition of such components. Research at the NASA Glenn Research Center involves developing and utilizing an NDE technique that discloses distributed material changes that occur prior to the localized damage detected by the current methods of inspection. In a recent study, creep processes in a nickel-base alloy were the life-limiting condition of interest, and the NDE technique was acousto-ultrasonics (AU). AU is an NDE technique that utilizes two ultrasonic transducers to interrogate the condition of a test specimen. The sending transducer introduces an ultrasonic pulse at a point on the surface of the specimen while a receiving transducer detects the signal after it has passed through the material. The goal of the method is to correlate certain parameters of the detected waveform to characteristics of the material between the two transducers. Here, the waveform parameter of interest is the attenuation due to internal damping for which information is being garnered from the frequency domain. The parameters utilized to

  16. Age and metabolic risk factors associated with oxidatively damaged DNA in human peripheral blood mononuclear cells

    DEFF Research Database (Denmark)

    Løhr, Mille; Jensen, Annie; Eriksen, Louise; Grønbæk, Morten; Loft, Steffen; Møller, Peter

    2015-01-01

    , cholesterol and glycosylated hemoglobin (HbA1c). In the group of men, there were significant positive associations between alcohol intake, HbA1c and FPG-sensitive sites in multivariate analysis. The levels of metabolic risk factors were positively associated with age, yet only few subjects fulfilled all...

  17. Early age damage quantification of actively restrained concrete using inverse analysis

    Science.gov (United States)

    Albanna, Ali

    Early-age cracking can be a significant problem in concrete pavements, floors, and bridge decks. Cracking occurs when the volumetric changes associated with drying, hydration, and temperature reduction are prevented. Good knowledge about the characteristics of early age concrete is necessary to achieve reliable crack control. Volumetric changes due to shrinkage depend on the type of concrete and its components. It has been found that light weight aggregates can work as internal reservoir to supply the concrete matrix with water that is needed during the early age; this process is called internal curing. Also fibers can give more ductility to the concrete and produce less shrinkage. There is a need to better understand the effects of early age uniaxial restraint on long term concrete mechanical performance. In this study, two types of concrete were studied (high performance fiber reinforced concrete and ordinary concrete) under actively restrained loading conditions to assess the effect on the long term fracture toughness and energy. Single edge notched specimens having dimensions of 250 mm x 150 mm x 75 mm and a notch to depth ratio of 0.33 were caste and used in both direct tension and three point bending. The direct tension tests were carried out on a direct tension loading frame constructed in house that was supplied with two mechanical jacks and load cell.

  18. Growth and Potential Damage of Human Bone-Derived Cells on Fresh and Aged Fullerene C60 Films

    Directory of Open Access Journals (Sweden)

    Jiri Vacik

    2013-04-01

    Full Text Available Fullerenes are nanoparticles composed of carbon atoms arranged in a spherical hollow cage-like structure. Numerous studies have evaluated the therapeutic potential of fullerene derivates against oxidative stress-associated conditions, including the prevention or treatment of arthritis. On the other hand, fullerenes are not only able to quench, but also to generate harmful reactive oxygen species. The reactivity of fullerenes may change in time due to the oxidation and polymerization of fullerenes in an air atmosphere. In this study, we therefore tested the dependence between the age of fullerene films (from one week to one year and the proliferation, viability and metabolic activity of human osteosarcoma cells (lines MG-63 and U-2 OS. We also monitored potential membrane and DNA damage and morphological changes of the cells. After seven days of cultivation, we did not observe any cytotoxic morphological changes, such as enlarged cells or cytosolic vacuole formation. Furthermore, there was no increased level of DNA damage. The increasing age of the fullerene films did not cause enhancement of cytotoxicity. On the contrary, it resulted in an improvement in the properties of these materials, which are more suitable for cell cultivation. Therefore, fullerene films could be considered as a promising material with potential use as a bioactive coating of cell carriers for bone tissue engineering.

  19. Evaluation of microstructural damage and alteration of polytypes to determine the aging of silicon carbide

    Energy Technology Data Exchange (ETDEWEB)

    Koenig, T. W.; Mishra, B.; Olson, D. L. [Department of Metallurgical and Materials Engineering, Colorado School of Mines, Golden, CO 80401 (United States); Meshi, L.; Foxman, Z.; Landau, A. [Ben-Gurion University of the Negev at Beer-Sheva, P.O.B. 653 Beer Sheva, 84105 (Israel); Riesterer, J. L.; Kennedy, J. R. [Advanced Test Reactor, Idaho National Laboratory, Idaho Falls, ID 83415 (United States)

    2013-01-25

    Irradiated silicon carbide (SiC) exhibits higher carrier content but a decrease in conductivity with increased irradiation. It was theorized that this conflicting data was due to structural damage due to irradiation. This theory was supported by the fact that non-irradiated 50{mu}m thick SiC is transparent for visible light and the higher the irradiation dose, the material of the same thickness became less transparent. However, changes in microscopy and polyforms observed by transmission electron microscopy in SiC due to irradiation were minor. Although existence of different polymorphs of SiC was documented, direct proof of the proposed theory has not yet been achieved.

  20. Evaluation of microstructural damage and alteration of polytypes to determine the aging of silicon carbide

    International Nuclear Information System (INIS)

    Irradiated silicon carbide (SiC) exhibits higher carrier content but a decrease in conductivity with increased irradiation. It was theorized that this conflicting data was due to structural damage due to irradiation. This theory was supported by the fact that non-irradiated 50μm thick SiC is transparent for visible light and the higher the irradiation dose, the material of the same thickness became less transparent. However, changes in microscopy and polyforms observed by transmission electron microscopy in SiC due to irradiation were minor. Although existence of different polymorphs of SiC was documented, direct proof of the proposed theory has not yet been achieved.

  1. Alzheimer's Disease: An Exacerbation of Senile Phenoptosis.

    Science.gov (United States)

    Isaev, N K; Stelmashook, E V; Genrikhs, E E; Oborina, M V; Kapkaeva, M R; Skulachev, V P

    2015-12-01

    Alzheimer's disease is characterized by progressive memory loss and cognitive decline accompanied by degeneration of neuronal synapses, massive loss of neurons in the brain, eventually resulting in complete degradation of personality and death. Currently, the cause of the disease is not fully understood, but it is believed that the person's age is the major risk factor for development of Alzheimer's disease. People who have survived after cerebral stroke or traumatic brain injury have substantially increased risk of developing Alzheimer's disease. Social exclusion, low social activity, physical inactivity, poor mental performance, and low level of education are among risk factors for development of this neurodegenerative disease, which is consistent with the concept of phenoptosis (Skulachev, V. P., et al. (1999) Biochemistry (Moscow), 64, 1418-1426; Skulachev, M. V., and Skulachev, V. P. (2014) Biochemistry (Moscow), 79, 977-993) stating that rate of aging is related to psychological and social aspects in human behavior. Here we assumed that Alzheimer's disease might be considered as an exacerbation of senile phenoptosis. If so, then development of this disease could be slowed using mitochondria-targeted antioxidants due to the accumulated data demonstrating a link between mitochondrial dysfunction and oxidative stress both with normal aging and Alzheimer's disease. PMID:26638682

  2. COPD exacerbation: anthropometric characteristics of patients and the frequency of hospital admissions

    Directory of Open Access Journals (Sweden)

    Gashynova K.Y.

    2014-11-01

    Full Text Available Exceptional importance of exacerbations for COPD course prognosing was reflected in the GOLD, 2011, where the number of exacerbations during the past year has been recognized as one of the main criteria of the future risks for patients. The aim of study was to determine the anthropometric indicators that increase the risk of re-hospitalization due to acute exacerbation of COPD. A retrospective analysis of medical records of inpatients who were hospitalized with COPD exacerbation to therapeutic department of CI "Dnipropetrovs’k sixth municipal clinical hospital" of Dnipropetrovsk regional council" during three years was done. It was established that neither sex, nor height, nor weight affect the rate of hospitalization due to COPD exacerbations. Older age is not a factor that increases the risk of hospitalization due to COPD exacerbation (despite the fact that the majority of hospitalized patients were elderly patients, 37% of them were persons of potentially working age. Severe exacerbation of COPD may occur in any patients with, even one year, experience of the disease. Among anthropometric indices, the most important predictor of re-hospitalization due to exacerbation of COPD is BMI<18.5, so its calculation is advisable in long-term observation of patients.

  3. Ageing tests of radiation damaged lasers and photodiodes for the CMS experiment at CERN

    CERN Document Server

    Gill, K; Batten, J; Cervelli, G; Grabit, R; Jensen, F; Troska, Jan K; Vasey, F

    2000-01-01

    The effects of thermally accelerated ageing in irradiated and unirradiated 1310 nm InGaAsP edge-emitting lasers and InGaAs p-i-n photodiodes are presented. 40 lasers (20 irradiated) and 30 photodiodes (19 irradiated) were aged for 4000 hours at 80 degrees C. Periodic measurements were made of laser threshold and efficiency, and p-i-n leakage current and photocurrent. There were no sudden failures and there was very little wearout related degradation in either unirradiated or irradiated sample groups. The results suggest that the tested devices have a sufficiently long lifetime to operate for at least 10 years inside the Compact Muon Solenoid experiment despite being exposed to a harsh radiation environment. (19 refs).

  4. COPD exacerbations: an evidence-based review

    Directory of Open Access Journals (Sweden)

    Robbins RA

    2012-07-01

    Full Text Available COPD exacerbations are a major source of COPD morbidity, mortality and cost. Exacerbations tend to become more frequent as COPD progresses with the cause assumed to be infectious in about 80% of patients. The mainstay of management is inhaled bronchodilators with judicious use of oxygen, antibiotics, corticosteroids and assisted ventilation. Recent studies have examined strategies to prevent exacerbations of COPD including use of macrolide antibiotics and self-management education.

  5. COPD exacerbations: an evidence-based review

    OpenAIRE

    Robbins RA

    2012-01-01

    COPD exacerbations are a major source of COPD morbidity, mortality and cost. Exacerbations tend to become more frequent as COPD progresses with the cause assumed to be infectious in about 80% of patients. The mainstay of management is inhaled bronchodilators with judicious use of oxygen, antibiotics, corticosteroids and assisted ventilation. Recent studies have examined strategies to prevent exacerbations of COPD including use of macrolide antibiotics and self-management education.

  6. Study of the fatigue behaviour and damage of a aged duplex stainless steel

    International Nuclear Information System (INIS)

    Cast duplex stainless steels are commonly used in components of pressurized water reactors primary circuit. When submitted to in-service temperatures embrittlement occurs because of the nucleation and growth of a harder phase in the ferrite by spinodal composition. Macrostructure of this steel (ferritic primary grain size is about 4-5 mm) and embrittlement of ferrite due to aging lead to a very high scattering of mechanical properties for monotonous loadings. We showed that, in spite of this macrostructure, the cyclic behaviour of aged duplex stainless steels fits usual Manson-Coffin law while initial hardening is followed by softening, in part because of the demodulation of the composition. The fatigue crack propagation rate of material follows a Paris law. While crack initiation mainly appears next to the millimetric cast defects, fatigue crack propagation remains a continuous mechanism. Ferritic and austenitic elements break successively (ferrite first breaks by cleavage, then austenite breaks by ductile fatigue). In spite of the fact that the aged ferrite is embrittled, cleavage microcracks, for load levels examined, seldom appear in ferrite at the crack tip and on both sides of the main crack. Effects of cast defects and crystallographic ferrite orientation were also studied. Propagation fatigue crack behaviour was modeled assuming that the crack tip material behaves as if it was submitted to low cycle fatigue loadings. If we consider a homogeneous material, results are in good agreement with experiments. (authors)

  7. Cadmium, type 2 diabetes, and kidney damage in a cohort of middle-aged women

    Energy Technology Data Exchange (ETDEWEB)

    Barregard, Lars, E-mail: lars.barregard@amm.gu.se [Occupational and Environmental Medicine, Sahlgrenska University Hospital and University of Gothenburg P.O. Box 414, SE-405 30 Gothenburg (Sweden); Bergström, Göran, E-mail: goran.bergstrom@wlab.gu.se [Sahlgrenska Center for Cardiovascular and Metabolic Research, Wallenberg Laboratory, Sahlgrenska University Hospital, SE-405 30 Gothenburg (Sweden); Department of Molecular and Clinical Medicine, University of Gothenburg, SE-405 30 Gothenburg (Sweden); Fagerberg, Björn, E-mail: bjorn.fagerberg@wlab.gu.se [Sahlgrenska Center for Cardiovascular and Metabolic Research, Wallenberg Laboratory, Sahlgrenska University Hospital, SE-405 30 Gothenburg (Sweden); Department of Molecular and Clinical Medicine, University of Gothenburg, SE-405 30 Gothenburg (Sweden)

    2014-11-15

    Background: It has been proposed that diabetic patients are more sensitive to the nephrotoxicity of cadmium (Cd) compared to non-diabetics, but few studies have examined this in humans, and results are inconsistent. Aim: To test the hypothesis that women with type 2 diabetes mellitus (DM) or impaired glucose tolerance (IGT) have higher risk of kidney damage from cadmium compared to women with normal glucose tolerance (NGT). Methods: All 64-year-old women in Gothenburg, Sweden, were invited to a screening examination including repeated oral glucose tolerance tests. Random samples of women with DM, IGT, and NGT were recruited for further clinical examinations. Serum creatinine was measured and used to calculate estimated glomerular filtration rate (eGFR). Albumin (Alb) and retinol-binding protein (RBP) were analyzed in a 12 h urine sample. Cadmium in blood (B-Cd) and urine (U-Cd) was determined using inductively coupled plasma mass spectrometry. Associations between markers of kidney function (eGFR, Alb, and RBP) and quartiles of B-Cd and U-Cd were evaluated in models, including also blood pressure and smoking habits. Results: The mean B-Cd (n=590) was 0.53 µg/L (median 0.34 µg/L). In multivariable models, a significant interaction was seen between high B-Cd (upper quartile, >0.56 µg/L) and DM (point estimate +0.40 mg Alb/12 h, P=0.04). In stratified analyzes, the effect of high B-Cd on Alb excretion was significant in women with DM (53% higher Alb/12 h, P=0.03), but not in women with IGT or NGT. Models with urinary albumin adjusted for creatinine showed similar results. In women with DM, the multivariable odds ratio (OR) for microalbuminuria (>15 mg/12 h) was increased in the highest quartile of B-Cd vs. B-Cd quartiles 1–3 in women with DM (OR 4.2, 95% confidence interval 1.1–12). No such effect was found in women with IGT or NGT. There were no associations between B-Cd and eGFR or excretion of RBP, and no differences between women with DM, IGT, or NGT

  8. Cadmium, type 2 diabetes, and kidney damage in a cohort of middle-aged women

    International Nuclear Information System (INIS)

    Background: It has been proposed that diabetic patients are more sensitive to the nephrotoxicity of cadmium (Cd) compared to non-diabetics, but few studies have examined this in humans, and results are inconsistent. Aim: To test the hypothesis that women with type 2 diabetes mellitus (DM) or impaired glucose tolerance (IGT) have higher risk of kidney damage from cadmium compared to women with normal glucose tolerance (NGT). Methods: All 64-year-old women in Gothenburg, Sweden, were invited to a screening examination including repeated oral glucose tolerance tests. Random samples of women with DM, IGT, and NGT were recruited for further clinical examinations. Serum creatinine was measured and used to calculate estimated glomerular filtration rate (eGFR). Albumin (Alb) and retinol-binding protein (RBP) were analyzed in a 12 h urine sample. Cadmium in blood (B-Cd) and urine (U-Cd) was determined using inductively coupled plasma mass spectrometry. Associations between markers of kidney function (eGFR, Alb, and RBP) and quartiles of B-Cd and U-Cd were evaluated in models, including also blood pressure and smoking habits. Results: The mean B-Cd (n=590) was 0.53 µg/L (median 0.34 µg/L). In multivariable models, a significant interaction was seen between high B-Cd (upper quartile, >0.56 µg/L) and DM (point estimate +0.40 mg Alb/12 h, P=0.04). In stratified analyzes, the effect of high B-Cd on Alb excretion was significant in women with DM (53% higher Alb/12 h, P=0.03), but not in women with IGT or NGT. Models with urinary albumin adjusted for creatinine showed similar results. In women with DM, the multivariable odds ratio (OR) for microalbuminuria (>15 mg/12 h) was increased in the highest quartile of B-Cd vs. B-Cd quartiles 1–3 in women with DM (OR 4.2, 95% confidence interval 1.1–12). No such effect was found in women with IGT or NGT. There were no associations between B-Cd and eGFR or excretion of RBP, and no differences between women with DM, IGT, or NGT

  9. Influence of age and sex on the spontaneous DNA damage detected by micronucleus test and comet assay in mice peripheral blood cells.

    Science.gov (United States)

    Heuser, Vanina Dahlström; de Andrade, Vanessa Moraes; Peres, Alessandra; Gomes de Macedo Braga, Luisa Maria; Bogo Chies, José Arthur

    2008-10-01

    We have investigated the normal variations in basal DNA damage detected by Comet assay in leukocytes and micronucleated erythrocytes (MNE) using the Micronucleus test (MN) in peripheral blood cells from 45 female and male mice from different age groups (newborns, 3.5, 12, and 104 weeks) to clarify age and sex-related changes. Comparison of basal DNA damage detected by Comet assay showed significantly increased values in 104 weeks old mice in relation to the other ages (P < or = 0.01), and newborn mice showed higher values in MNE frequency when compared to all the other groups (P < or = 0.01). A positive correlation was observed between Damage Frequency (r =0.382, P = 0.010) and Damage Index (r = 0.640, P < 0.001) and age. Age was also correlated with the ratio of polychromatic erythrocytes/normachromatic erythrocytes (PCE/NCE) (r = -0.473, P = 0.001), and the MNE frequency was positively correlated with the ratio of PCE/NCE (r = 0.454, P = 0.002). These results suggest an age-related slow down of DNA repair efficiency of DNA damage and/or DNA damage accumulation. Furthermore, data on the spontaneous MNE frequency indicate that the reticuloendothelial system matures with age, and there is a close relationship between erythropoiesis and micronucleus induction in erythrocytes. The influence of sex in the parameters analyzed was less clear. In conclusion, age seems to influence in basal DNA damage and should be considered in genotoxicity studies using mice. Finally, comparisons between assays must be made with care when different cells are compared (e.g. leukocytes and erythrocytes), as found with the Comet assay and MN test. PMID:18675925

  10. Infective Exacerbation of Pasteurella multocida

    Science.gov (United States)

    Hamada, Mayumi; Elshimy, Noha; Abusriwil, Hatem

    2016-01-01

    An 89-year-old lady presented with a one-day history of shortness of breath as well as a cough productive of brown sputum. Her medical history was significant for chronic obstructive pulmonary disease (COPD). She was in severe type one respiratory failure and blood tests revealed markedly raised inflammatory markers; however her chest X-ray was clear. On examination there was bronchial breathing with widespread crepitations and wheeze. She was treated as per an infective exacerbation of COPD. Subsequent blood cultures grew Pasteurella multocida, a common commensal in the oropharynx of domesticated animals. The patient was then asked about any contact with animals, after which she revealed she had a dog and was bitten on her left hand the day before admission. We should not forget to enquire about recent history of injuries or animal bites when patients present acutely unwell. She made a complete recovery after treatment with penicillin. PMID:26942025

  11. Propagation of cracks and damage in non aging linear viscoelastic media

    International Nuclear Information System (INIS)

    Most of France's energy is nuclear. The reactor building comprises a internal and external containment. The internal containment is prestressed to limit the flow of leakage in the internal-external space. The prestress decreases during time by the creep of concrete. It may propagate the cracks by the accidental internal pressure. So we define two research problems: propagation of macro-cracks in viscoelastic structure; effective behavior of micro-cracked viscoelastic material. Firstly, we develop a Burger viscoelastic model of concrete with two approaches: numerical and analytical. Then we solve the problem of single cracks in developing thermodynamically the concept of energy release rate. In the third part we develop a viscoelastic model to study the effective behavior of micro-cracked materials in the case without propagation. The problem of propagation of microcracks is then studied by a numerical approach based on the 'representative pattern morphology'. These studies are finally applied to solve the problems of crack propagation and damage of containment under accidental internal pressure. (authors)

  12. Ageing Fxr Deficient Mice Develop Increased Energy Expenditure, Improved Glucose Control and Liver Damage Resembling NASH

    OpenAIRE

    Bjursell, Mikael; Wedin, Marianne; Admyre, Therése; Hermansson, Majlis; Böttcher, Gerhard; Göransson, Melker; Lindén, Daniel; Bamberg, Krister; Oscarsson, Jan; Bohlooly-Y, Mohammad

    2013-01-01

    Nuclear receptor subfamily 1, group H, member 4 (Nr1h4, FXR) is a bile acid activated nuclear receptor mainly expressed in the liver, intestine, kidney and adrenal glands. Upon activation, the primary function is to suppress cholesterol 7 alpha-hydroxylase (Cyp7a1), the rate-limiting enzyme in the classic or neutral bile acid synthesis pathway. In the present study, a novel Fxr deficient mouse line was created and studied with respect to metabolism and liver function in ageing mice fed chow d...

  13. Increasing Safety and Reducing Environmental Damage Risk from Aging High-Level Radioactive Waste Tanks

    International Nuclear Information System (INIS)

    There exists a paramount need for improved understanding the behavior of high-level nuclear waste containers and the impact on structural integrity in terms of leak tightness and mechanical stability. The current program aims to develop and verify models of crack growth in high level waste tanks under accidental overloads such as ground settlement, earthquakes and airplane crashes based on extending current fracture mechanics methods. While studies in fracture have advanced, the mechanics have not included extensive crack growth. For problems at the INEEL, Savannah River Site and Hanford there are serious limitations to current theories regarding growth of surface cracks through the thickness and the extension of through-thickness cracks. We propose to further develop and extend slip line fracture mechanics (SLFM, a ductile fracture modeling methodology) and, if need be, other ductile fracture characterizing approaches with the goal of predicting growth of surface cracks to the point o f penetration of the opposing surface. Ultimately we aim to also quantify the stress and displacement fields surrounding a growing crack front (slanted and tunneled) using generalized plane stress and fully plastic, three-dimensional finite element analyses. Finally, we will investigate the fracture processes associated with the previously observed transition of stable ductile crack growth to unstable cleavage fracture to include estimates of event probability. These objectives will build the groundwork for a reliable predictive model of fracture in the HLW storage tanks that will also be applicable to standardized spent nuclear fuel storage canisters. This predictive capability will not only reduce the potential for severe environmental damage, but will also serve to guide safe retrieval of waste. This program was initiated in November of 2001

  14. Taking into account of the aging and the damage in the size determination of composite materials structures

    International Nuclear Information System (INIS)

    The aim of this study was to better understand the aging of glass fibres-epoxy composites exposed to humid conditions and loading so as to predict its effects on the lifetimes of composite structures. Water diffusion was first experimentally investigated by gravimetric method to determine water sorption kinetics for different humid conditions. A Fickian model of diffusion could describe the results obtained. Specimens, saturated at different levels, were mechanically characterised. Decreases of mechanical properties as a function of water uptake were revealed by tensile tests. Damage by cracking and the coupling with humidity were then studied. Differences between reversible and irreversible changes in properties were revealed and analysed in detail. A predictive model taking into account effects due to water and/or mechanical loading is proposed, using finite element method. As a first step, in modelling the diffusion process, the non-uniform water distribution across the composite are determined for any conditions (temperature, humidity, aging time). The resulting mechanical properties of the material, as a function of the absorbed water concentration, are determined in each point. Then, diffusion/mechanic coupled calculation allows to determine material global properties from properties at each point. It is then possible to predict continuous evolution of rigidity during aging time, at all stages of water absorption and matrix cracking, for any condition (temperature, humidity, thickness, mechanical loading level). (author)

  15. Exacerbations of asthma during pregnancy: Impact on pregnancy complications and outcome.

    Science.gov (United States)

    Ali, Z; Hansen, A V; Ulrik, C S

    2016-05-01

    Asthma is common among pregnant women, and the incidence of asthma exacerbations during pregnancy is high. This literature review provides an overview of the impact of exacerbations of asthma during pregnancy on pregnancy-related complications. The majority of published retrospective studies reveal that asthma exacerbations during pregnancy increase the risk of pre-eclampsia, gestational diabetes, placental abruption and placenta praevia. Furthermore, these women also have higher risk for breech presentation, haemorrhage, pulmonary embolism, caesarean delivery, maternal admission to the intensive care unit and longer postpartum hospital stay. Asthma has been associated with increased risk of intrauterine growth retardation, small-for-gestational age, low birth weight, infant hypoglycaemia and preterm birth, but more recent prospective studies have not revealed significant associations with regard to these outcomes. In conclusion, asthma exacerbations during pregnancy are associated with complications of pregnancy, labour and delivery. Prevention of exacerbations is essential to reduce the risk of complications and poor outcome. PMID:26467747

  16. Chronic obstructive pulmonary disease exacerbation frequency and severity

    OpenAIRE

    Stafyla E; Kerenidi T; Gourgoulianis KI

    2013-01-01

    Eirini Stafyla, Theodora Kerenidi, Konstantinos I Gourgoulianis Respiratory Medicine Department, University of Thessaly Medical School, University Hospital of Larissa, Larissa, GreeceWe read with great interest the original work by Motegi et al1 comparing three multidimensional assessment systems – BODE (body mass index, obstruction, dyspnea, and exercise capacity) index, DOSE (dyspnea, obstruction, smoking, exacerbations) index and ADO (age, dyspnea, obstruction) index – for pred...

  17. Blood Eosinophils and Exacerbations in COPD

    DEFF Research Database (Denmark)

    Vedel-Krogh, Signe; Nielsen, Sune F; Lange, Peter; Vestbo, Jørgen; Nordestgaard, Børge G

    2015-01-01

    RATIONALE: Whether high blood eosinophils are associated with COPD exacerbations among individuals with COPD in the general population is largely unknown. OBJECTIVES: To test the hypothesis that high blood eosinophils predict COPD exacerbations. METHODS: Among 81,668 individuals from the Copenhagen...... General Population Study, we examined 7,225 with COPD based on spirometry. We recorded blood eosinophils at baseline and future COPD exacerbations longitudinally, defined as moderate (short-course treatment of systemic corticosteroids) or severe (hospitalization). We also assessed exacerbation risk in a...... subgroup of 203 COPD individuals with clinical COPD, defined as participants with ≥ 10 pack-years, FEV1 < 70% of predicted value and ≥ 1 moderate or severe exacerbation in the year prior to baseline. MEASUREMENTS AND MAIN RESULTS: During a median of 3.3 years of follow-up (range 0.03-8.1), 1,439 severe and...

  18. Optimizing antibiotic selection in treating COPD exacerbations

    Directory of Open Access Journals (Sweden)

    Attiya Siddiqi

    2008-03-01

    Full Text Available Attiya Siddiqi, Sanjay SethiDivision of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Veterans Affairs Western New York Health Care System and University of Buffalo, State University of New York, Buffalo, New York, USAAbstract: Our understanding of the etiology, pathogenesis and consequences of acute exacerbations of chronic obstructive pulmonary disease (COPD has increased substantially in the last decade. Several new lines of evidence demonstrate that bacterial isolation from sputum during acute exacerbation in many instances reflects a cause-effect relationship. Placebo-controlled antibiotic trials in exacerbations of COPD demonstrate significant clinical benefits of antibiotic treatment in moderate and severe episodes. However, in the multitude of antibiotic comparison trials, the choice of antibiotics does not appear to affect the clinical outcome, which can be explained by several methodological limitations of these trials. Recently, comparison trials with nontraditional end-points have shown differences among antibiotics in the treatment of exacerbations of COPD. Observational studies that have examined clinical outcome of exacerbations have repeatedly demonstrated certain clinical characteristics to be associated with treatment failure or early relapse. Optimal antibiotic selection for exacerbations has therefore incorporated quantifying the risk for a poor outcome of the exacerbation and choosing antibiotics differently for low risk and high risk patients, reserving the broader spectrum drugs for the high risk patients. Though improved outcomes in exacerbations with antibiotic choice based on such risk stratification has not yet been demonstrated in prospective controlled trials, this approach takes into account concerns of disease heterogeneity, antibiotic resistance and judicious antibiotic use in exacerbations.Keywords: COPD, exacerbation, bronchitis, antibiotics

  19. An Experimental Investigation On Minimum Compressive Strength Of Early Age Concrete To Prevent Frost Damage For Nuclear Power Plant Structures In Cold Climates

    International Nuclear Information System (INIS)

    Concrete undergoing early frost damage in cold weather will experience significant loss of not only strength, but also of permeability and durability. Accordingly, concrete codes like ACI-306R prescribe a minimum compressive strength and duration of curing to prevent frost damage at an early age and secure the quality of concrete. Such minimum compressive strength and duration of curing are mostly defined based on the strength development of concrete. However, concrete subjected to frost damage at early age may not show a consistent relationship between its strength and durability. Especially, since durability of concrete is of utmost importance in nuclear power plant structures, this relationship should be imperatively clarified. Therefore, this study verifies the feasibility of the minimum compressive strength specified in the codes like ACI-306R by evaluating the strength development and the durability preventing the frost damage of early age concrete for nuclear power plant. The results indicate that the value of 5 MPa specified by the concrete standards like ACI-306R as the minimum compressive strength to prevent the early frost damage is reasonable in terms of the strength development, but seems to be inappropriate in the viewpoint of the resistance to chloride ion penetration and freeze-thaw. Consequently, it is recommended to propose a minimum compressive strength preventing early frost damage in terms of not only the strength development, but also in terms of the durability to secure the quality of concrete for nuclear power plants in cold climates

  20. Epigallocatechin-3-Gallate Protects Erythrocyte Ca2+-ATPase and Na+/K+-ATPase Against Oxidative Induced Damage During Aging in Humans

    Directory of Open Access Journals (Sweden)

    Prabhanshu Kumar

    2014-10-01

    Full Text Available Purpose: The main purpose of this study was to investigate the protective role of epigallocatechin-3-gallate on tertiary butyl hydroperoxide induced oxidative damage in erythrocyte during aging in humans. Methods: Human erythrocyte membrane bound Ca2+-ATPase and Na+/K+-ATPase activities were determined as a function of human age. Protective role of epigallocatechin-3-gallate was evaluated by in vitro experiments by adding epigallocatechin-3-gallate in concentration dependent manner (final concentration range 10-7M to 10-4M to the enzyme assay medium. Oxidative stress was induced in vitro by incubating washed erythrocyte ghosts with tertiary butyl hydroperoxide (10-5 M final concentration. Results: We have reported concentration dependent effect of epigallocatechin-3-gallate on tertiary butyl hydroperoxide induced damage on activities of Ca2+-ATPase and Na+/K+-ATPase during aging in humans. We have detected a significant (p < 0.001 decreased activity of Ca2+-ATPase and Na+/K+ -ATPase as a function of human age. Epigallocatechin-3-gallate protected ATPases against tertiary butyl hydroperoxide induced damage in concentration dependent manner during aging in humans. Conclusion: Epigallocatechin-3-gallate is a powerful antioxidant that is capable of protecting erythrocyte Ca2+-ATPase and Na+/K+ -ATPase against oxidative stress during aging in humans. We may propose hypothesis that a high intake of catechin rich diet may provide some protection against development of aging and age related diseases.

  1. Montelukast reduces asthma exacerbations in 2- to 5-year-old children with intermittent asthma

    DEFF Research Database (Denmark)

    Bisgaard, Hans; Zielen, Stefen; Garcia-Garcia, María Luz;

    2005-01-01

    The PREVIA study was designed to investigate the role of montelukast, a leukotriene receptor antagonist, in the prevention of viral-induced asthma exacerbations in children aged 2 to 5 years with a history of intermittent asthma symptoms. The study was a 12-month multicenter, double-blind, parallel......-group study of patients with asthma exacerbations associated with respiratory infections and minimal symptoms between episodes. Patients were randomized to receive oral montelukast 4 or 5 mg (depending on age) (n = 278) or placebo (n = 271) once per day for 12 months. Caregivers recorded children's symptoms......, beta-agonist use, and health care resource use in a diary card. Over 12 months of therapy, montelukast significantly reduced the rate of asthma exacerbations by 31.9% compared with placebo. The average rate of exacerbation episodes per patient was 1.60 episodes per year on montelukast compared with 2...

  2. Sun Damage

    Science.gov (United States)

    ... rash and rashes clinical tools newsletter | contact Share | Sun Damage A A A The sun has a profound effect over years of exposure ... changes. Exposure to ultraviolet (UV) light from the sun accounts for most premature skin aging. Many skin ...

  3. Update on work-exacerbated asthma

    OpenAIRE

    Tarlo, Susan M

    2016-01-01

    Work-exacerbated asthma (WEA) is the term used to describe the worsening of asthma related to work but not the causation of asthma by work. It is common and has been reported to occur for 21.5% of working asthmatics on average. The frequency and severity may range from a single mild exacerbation that may lead to no time lost at work up to daily or severe exacerbations that may require a permanent change in work. Reports from general population surveys and primary care settings include more pa...

  4. DNA damage-induced metaphase I arrest is mediated by the spindle assembly checkpoint and maternal age

    OpenAIRE

    Marangos, P; Stevense, M.; Niaka, K.; Lagoudaki, M.; Nabti, I.; Jessberger, R.; Carroll, J.

    2015-01-01

    In mammalian oocytes DNA damage can cause chromosomal abnormalities that potentially lead to infertility and developmental disorders. However, there is little known about the response of oocytes to DNA damage. Here we find that oocytes with DNA damage arrest at metaphase of the first meiosis (MI). The MI arrest is induced by the spindle assembly checkpoint (SAC) because inhibiting the SAC overrides the DNA damage-induced MI arrest. Furthermore, this MI checkpoint is compromised in oocytes fro...

  5. Acute exacerbation of airspace enlargement with fibrosis

    OpenAIRE

    Tomoyuki Kakugawa; Kazuhiro Tabata; Daiki Ogawara; Tomoshi Tsuchiya; Shintaro Hara; Noriho Sakamoto; Yuji Ishimatsu; Kazuto Ashizawa; Takeshi Nagayasu; Junya Fukuoka; Shigeru Kohno

    2014-01-01

    In 2008, Kawabata et al. described a lesion which they termed “airspace enlargement with fibrosis” that could be included on the spectrum of smoking-related interstitial lung diseases. This group also reported that patients with airspace enlargement with fibrosis but without coexisting interstitial pneumonia of another type had no acute exacerbations and favorable prognoses on clinical follow-up. Here we describe the first case, to our knowledge, of acute exacerbation of airspace enlargement ...

  6. COPD exacerbations by disease severity in England

    OpenAIRE

    Merinopoulou E; Raluy-Callado M; Ramagopalan S; MacLachlan S; Khalid JM

    2016-01-01

    Evie Merinopoulou,1 Mireia Raluy-Callado,1 Sreeram Ramagopalan,1 Sharon MacLachlan,1 Javaria Mona Khalid2 1Real-World Evidence, Evidera, 2Takeda Development Centre Europe Ltd, London, UK Objectives: Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with accelerated disease progression and are important drivers of health care resource utilization. The study aimed to quantify the rates of COPD exacerbations in England and assess health care resource utilization by ...

  7. Management of acute exacerbations in multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Ontaneda Daniel

    2009-01-01

    Full Text Available A key component of multiple sclerosis is the occurrence of episodes of clinical worsening with either new symptoms or an increase in older symptoms over a few days or weeks. These are known as exacerbations of multiple sclerosis. In this review, we summarize the pathophysiology and treatment of exacerbations and describe how they are related to the overall management of this disease.

  8. Exacerbations of Chronic Obstructive Pulmonary Disease

    OpenAIRE

    Garvey, Christine; Ortiz, Gabriel

    2012-01-01

    Epidemiologic data indicate that chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality. Patients with poorly managed COPD are likely to experience exacerbations that require emergency department visits or hospitalization—two important drivers contributing to escalating healthcare resource use and costs associated with the disease. Exacerbations also contribute to worsening lung function and negative outcomes in COPD. The aim of this review is to present th...

  9. Age- and time interval-specific gamma radiation-induced DNA damage in adult maize weevils, Sitophilus zeamais Motschulsky, assessed using comet assays.

    Science.gov (United States)

    Hasan, Md Mahbub; Todoriki, Setsuko; Miyanoshita, Akihiro; Imamura, Taro

    2012-01-24

    The gamma radiation-induced DNA damage in adult maize weevils, Sitophilus zeamais Motschulsky (Coleoptera: Curculionidae), was assessed using single-cell electrophoresis (comet assay). Analysis of DNA damage following 0.5 and 1.0 kGy of gamma radiation was performed using cells from 1- and 15-day-old adults. Gamma-irradiated adults from both age groups showed typical DNA fragmentation, whereas cells from non-irradiated adults showed more intact DNA than young S. zeamais. Investigations using the comet assay showed that tail length, % tail DNA and % DNA damage all increased in adults of both age groups when compared to the control insects. A maximum comet length of 227.33 μm was recorded for 15-day-old adults at 24h after irradiation with 1.0 kGy and a minimum of 50.12 μm for 1-day-old adults at 0 h after irradiation with 0.5 kGy. The percentage of DNA damage increased up to 57.31% and 68.15% for 1- and 15-day-old adults, respectively, at 24h after irradiation with 1.0 kGy, whereas only 8.58% and 12.22% DNA damage were observed in the control batches. The results also showed that percentage of DNA damage increased at 24h after irradiation compared to that at 0 h. However, further studies are needed to confirm these results. PMID:22142832

  10. Age-dependent loss of cholinergic neurons in learning and memory-related brain regions and impaired learning in SAMP8 mice with trigeminal nerve damage.

    Science.gov (United States)

    He, Yifan; Zhu, Jihong; Huang, Fang; Qin, Liu; Fan, Wenguo; He, Hongwen

    2014-11-15

    The tooth belongs to the trigeminal sensory pathway. Dental damage has been associated with impairments in the central nervous system that may be mediated by injury to the trigeminal nerve. In the present study, we investigated the effects of damage to the inferior alveolar nerve, an important peripheral nerve in the trigeminal sensory pathway, on learning and memory behaviors and structural changes in related brain regions, in a mouse model of Alzheimer's disease. Inferior alveolar nerve transection or sham surgery was performed in middle-aged (4-month-old) or elderly (7-month-old) senescence-accelerated mouse prone 8 (SAMP8) mice. When the middle-aged mice reached 8 months (middle-aged group 1) or 11 months (middle-aged group 2), and the elderly group reached 11 months, step-down passive avoidance and Y-maze tests of learning and memory were performed, and the cholinergic system was examined in the hippocampus (Nissl staining and acetylcholinesterase histochemistry) and basal forebrain (choline acetyltransferase immunohistochemistry). In the elderly group, animals that underwent nerve transection had fewer pyramidal neurons in the hippocampal CA1 and CA3 regions, fewer cholinergic fibers in the CA1 and dentate gyrus, and fewer cholinergic neurons in the medial septal nucleus and vertical limb of the diagonal band, compared with sham-operated animals, as well as showing impairments in learning and memory. Conversely, no significant differences in histology or behavior were observed between middle-aged group 1 or group 2 transected mice and age-matched sham-operated mice. The present findings suggest that trigeminal nerve damage in old age, but not middle age, can induce degeneration of the septal-hippocampal cholinergic system and loss of hippocampal pyramidal neurons, and ultimately impair learning ability. Our results highlight the importance of active treatment of trigeminal nerve damage in elderly patients and those with Alzheimer's disease, and indicate that

  11. Oxidative stress during aging and in Alzheimer's disease : a comparative study of oxidative damage and antioxidant enzymatic activities in mouse models and human brain tissue

    OpenAIRE

    Schüssel, Katrin

    2005-01-01

    The hypothesis that oxidative stress plays a role in the pathogenesis of Alzheimer’s disease (AD) was tested by studying oxidative damage, acitvities of antioxidant enzymes and levels of reactive oxygen species (ROS) in several models. To this end, mouse models transgenic for mutant presenilin (PS1M146L) as well as mutant amyloid precursor protein (APP) and human post mortem brain tissue from sporadic AD patients and age-matched controls were studied. Aging leads to an upregulation of antioxi...

  12. H2O2-mediated DNA damage and repair in the brain cells in the aging rats detected by comet assay

    Institute of Scientific and Technical Information of China (English)

    Suming ZhangM.D., Ph.D; Zongchao Han, M.D.; Siyu Fang, M.D.; Ruan Yang, M.D; Wei Wang, M.D., Ph. D

    2000-01-01

    Objective: To identify the relation between DNA damage susceptibility/ DNA repair capability and aging process after insults, an observation of H2O2_induced DNA damage and the kinetics of DNA repair in senescent murine brain cells with the alkaline single cell gel electrophoresis (SCGE/Comet assay) was made. Methods: The dissociated brain cells harvested in the area of the cerebral cortex, hippocampus, basal gang]ion from 3-month (n=10), 8-month (n=8) and 26-month (n=5) old rats were respectively treated with H2O2 in gradient doses for 10 min, or without H2O2 as controls. The cells embedded in agarose were lysed, helix-untied, electrophoresed, stained with a fluorescence DNA binding stain, viewed under a fluorescence microscope. Individual image was optically recorded. The frequency of the tailed cells and the grade of tails wereused to analyze single strand breaks of DNA and injury intensity. Results: By the cell and DNA image like comets, a linear increase was noticed in vulnerability of DNA both to H2O2 doses and to the age. Regarding the damaged region of the brain, the cortex cells were more vulnerable to the insult than the hippocampus/basal ganglionic cells. Whatever aging or not the cells were, the maximum of ratio of DNA repair was only within 1 hour during the incubation for 0.5-4 hours after the insults. Furthermore, the more aging, the less ratio of DNA repair of sick cells. Conclusion: The DNA damagesusceptibility and the DNA repair capability of individual cells, whatever its age is, can be detected by this brain cell injury model. Comet assay is a sensitive way to find out DNA damage and repair of the cells. It should be more difficult for the cells to cope with an acute and excessive than with a persistent, chronic and mild DNA damage which is more related to an accumulating injury, the aging.

  13. Effects of N-acetylcysteine on asthma exacerbation.

    Science.gov (United States)

    Aliyali, Masoud; Poorhasan Amiri, Ali; Sharifpoor, Ali; Zalli, Fatemeh

    2010-06-01

    Airway mucus hypersecretion and increased oxidative stress are clinical and pathophysiological features of asthma exacerbation. We studied effects of N-acetylcysteine (NAC) as a mucolytic and antioxidant agent in asthma exacerbation. In this randomized, single-blinded, placebo-controlled study 50 patients ( 17 male, 33 female, mean age 48.94+/-13.68) with asthma exacerbation were randomized to receive either oral 600 mg b.d. N-acetylcysteine or placebo in addition to standard treatment during 5 days hospitalization. Daily measurements of wheezing, dyspnea, cough, sputum, expectoration, night sleep scores and morning PEFR were performed. There was no significant difference in wheezing score between patients assigned NAC and those assigned placebo in day 5(0.84[SD 0.94] VS 0.87[SD 0.79]) and also in cough score (0.72[SD 0.84] VS 0.79[SD 0.97]), dyspnea score (0.84[SD 1.06] VS 0.91[SD 1.01]), sputum score(0.79[SD 0.83] VS 0.62[SD 0.71]), expectoration score(0.79[SD 0.97] VS 0.83[SD 1.09]), night sleep score(1[SD 1.17] VS 0.67[SD 0.98] and morning PEFR (256[SD 96.36] VS 282[SD 98.86]). We concluded that addition of N-acetylcysteine to usual asthma medication has no significant effect in treatment of asthma exacerbation. PMID:20683104

  14. The Relationship Between 24-Hour Symptoms and COPD Exacerbations and Healthcare Resource Use

    DEFF Research Database (Denmark)

    Miravitlles, Marc; Worth, Heinrich; Soler-Cataluña, Juan José;

    2016-01-01

    This observational study assessed the relationship between nighttime, early-morning and daytime chronic obstructive pulmonary disease (COPD) symptoms and exacerbations and healthcare resource use. COPD symptoms were assessed at baseline in patients with stable COPD using a standardised...... questionnaire during routine clinical visits. Information was recorded on exacerbations and healthcare resource use during the year before baseline and during a 6-month follow-up period. The main objective of the analysis was to determine the predictive nature of current symptoms for future exacerbations and...... healthcare resource use. 727 patients were eligible (65.8% male, mean age: 67.2 years, % predicted forced expiratory volume in 1 second: 52.8%); 698 patients (96.0%) provided information after 6 months. Symptoms in any part of the day were associated with a prior history of exacerbations (all p < 0.05) and...

  15. Work-related exacerbation of asthma.

    Science.gov (United States)

    Henneberger, Paul K; Hoffman, Christopher D; Magid, David J; Lyons, Ella E

    2002-01-01

    Adults with asthma who had been enrolled in an HMO for at least a year were requested to complete a questionnaire about their health status. Approximately 25% of the 1,461 participants responded positively to "Does your current work environment make your asthma worse?" and were classified as having workplace exacerbation of asthma. Those with workplace exacerbation were more likely to have never attended college, be current or former smokers, have a history of other respiratory diseases, have missed work or usual activities at least one day in the past for weeks, and report their asthma was moderate, severe, or very severe. Percentages with workplace exacerbation of asthma were highest for mining and construction (36%), wholesale and retail trade (33%), and public administration (33%), and lowest for educational services (22%), finance, insurance, and real estate (22%), and non-medical and non-educational services (18%). Future studies are needed for objective validation of self-reported workplace exacerbation, and to follow subjects prospectively to clarify the temporal sequence of workplace exacerbation and asthma severity, and how other respiratory conditions and smoking might contribute to work-related worsening of asthma. PMID:12412844

  16. Acute exacerbation of chronic hepatitis B virus infection in renal transplant patients

    Directory of Open Access Journals (Sweden)

    Christini Takemi Emori

    2014-12-01

    Full Text Available Introduction:There is scarce information regarding clinical evolution of HBV infection in renal transplant patients.Aims:To evaluate the prevalence of acute exacerbation in HBV-infected renal transplant patients and its association with the time after transplantation, presence of viral replication, clinical evolution, and use of antiviral prophylaxis.Materials and methods:HBV infected renal transplant patients who underwent regular follow-up visits at 6-month intervals were included in the study. The criteria adopted to characterize exacerbation were: ALT >5 × ULN and/or >3 × baseline level. Predictive factors of exacerbation evaluated were age, gender, time on dialysis, type of donor, post-transplant time, ALT, HBeAg, HBV-DNA, HCV-RNA, immunosuppressive therapy, and use of antiviral prophylaxis.Results:140 HBV-infected renal transplant patients were included (71% males; age 46 ±10 years; post-renal transplant time 8 ±5 years. During follow-up, 25% (35/140 of the patients presented exacerbation within 3.4 ±3 years after renal transplant. Viral replication was observed in all patients with exacerbation. Clinical and/or laboratory signs of hepatic insufficiency were present in 17% (6/35 of the patients. Three patients died as a consequence of liver failure. In univariate analysis variables associated with exacerbation were less frequent use of prophylactic/preemptive lamivudine and of mycophenolate mofetil. Lamivudine use was the only variable independently associated with exacerbation, with a protective effect.Conclusions:Acute exacerbation was a frequent and severe event in HBV-infected renal transplant patients. Prophylactic/preemptive therapy with antiviral drugs should be indicated for all HBsAg-positive renal transplant patients.

  17. Lipid Raft Size and Lipid Mobility in Non-raft Domains Increase during Aging and Are Exacerbated in APP/PS1 Mice Model of Alzheimer's Disease. Predictions from an Agent-Based Mathematical Model

    Science.gov (United States)

    Santos, Guido; Díaz, Mario; Torres, Néstor V.

    2016-01-01

    A connection between lipid rafts and Alzheimer's disease has been studied during the last decades. Mathematical modeling approaches have recently been used to correlate the effects of lipid composition changes in the physicochemical properties of raft-like membranes. Here we propose an agent based model to assess the effect of lipid changes in lipid rafts on the evolution and progression of Alzheimer's disease using lipid profile data obtained in an established model of familial Alzheimer's disease. We have observed that lipid raft size and lipid mobility in non-raft domains are two main factors that increase during age and are accelerated in the transgenic Alzheimer's disease mouse model. The consequences of these changes are discussed in the context of neurotoxic amyloid β production. Our agent based model predicts that increasing sterols (mainly cholesterol) and long-chain polyunsaturated fatty acids (LCPUFA) (mainly DHA, docosahexaenoic acid) proportions in the membrane composition might delay the onset and progression of the disease. PMID:27014089

  18. Three-month treatment response and exacerbation in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Lee, Jung Su; Rhee, Chin Kook; Yoo, Kwang Ha; Lee, Ji-Hyun; Yoon, Ho Il; Kim, Tae-Hyung; Kim, Woo Jin; Lee, JinHwa; Lim, Seong Yong; Park, Tai Sun; Lee, Jae Seung; Lee, Sei Won; Lee, Sang-Do; Oh, Yeon-Mok

    2015-01-01

    The aim of this study was to investigate relationships between acute exacerbation and Forced Expiratory Volume 1 second (FEV1) improvement after treatment with combined long-acting beta-agonist (LABA) and inhaled corticosteroid (ICS) in patients with chronic obstructive pulmonary disease (COPD). A total of 137 COPD patients were classified as responders or nonresponders according to FEV1 improvement after 3 months of LABA/ICS treatment in fourteen referral hospitals in Korea. Exacerbation occurrence in these two subgroups was compared over a period of 1 yr. Eighty of the 137 COPD patients (58.4%) were classified as responders and 57 (41.6%) as nonresponders. Acute exacerbations occurred in 25 patients (31.3%) in the responder group and in 26 patients (45.6%) in the nonresponder group (P=0.086). FEV1 improvement after LABA/ICS treatment was a significant prognostic factor for fewer acute exacerbations in a multivariate Cox proportional hazard model adjusted for age, sex, FEV1, smoking history, 6 min walk distance, body mass index, exacerbation history in the previous year, and dyspnea scale.Three-month treatment response to LABA/ICS might be a prognostic factor for the occurrence of acute exacerbation in COPD patients. PMID:25552883

  19. Age-dependent loss of cholinergic neurons in learning and memory-related brain regions and impaired learning in SAMP8 mice with trigeminal nerve damage

    Institute of Scientific and Technical Information of China (English)

    Yifan He; Jihong Zhu; Fang Huang; Liu Qin; Wenguo Fan; Hongwen He

    2014-01-01

    The tooth belongs to the trigeminal sensory pathway. Dental damage has been associated with impairments in the central nervous system that may be mediated by injury to the trigeminal nerve. In the present study, we investigated the effects of damage to the inferior alveolar nerve, an important peripheral nerve in the trigeminal sensory pathway, on learning and memory be-haviors and structural changes in related brain regions, in a mouse model of Alzheimer’s disease. Inferior alveolar nerve transection or sham surgery was performed in middle-aged (4-month-old) or elderly (7-month-old) senescence-accelerated mouse prone 8 (SAMP8) mice. When the middle-aged mice reached 8 months (middle-aged group 1) or 11 months (middle-aged group 2), and the elderly group reached 11 months, step-down passive avoidance and Y-maze tests of learn-ing and memory were performed, and the cholinergic system was examined in the hippocampus (Nissl staining and acetylcholinesterase histochemistry) and basal forebrain (choline acetyltrans-ferase immunohistochemistry). In the elderly group, animals that underwent nerve transection had fewer pyramidal neurons in the hippocampal CA1 and CA3 regions, fewer cholinergic ifbers in the CA1 and dentate gyrus, and fewer cholinergic neurons in the medial septal nucleus and vertical limb of the diagonal band, compared with sham-operated animals, as well as showing impairments in learning and memory. Conversely, no signiifcant differences in histology or be-havior were observed between middle-aged group 1 or group 2 transected mice and age-matched sham-operated mice. The present ifndings suggest that trigeminal nerve damage in old age, but not middle age, can induce degeneration of the septal-hippocampal cholinergic system and loss of hippocampal pyramidal neurons, and ultimately impair learning ability. Our results highlight the importance of active treatment of trigeminal nerve damage in elderly patients and those with Alzheimer’s disease, and

  20. Prevention of Acute Exacerbations of COPD

    Science.gov (United States)

    Bourbeau, Jean; Diekemper, Rebecca L.; Ouellette, Daniel R.; Goodridge, Donna; Hernandez, Paul; Curren, Kristen; Balter, Meyer S.; Bhutani, Mohit; Camp, Pat G.; Celli, Bartolome R.; Dechman, Gail; Dransfield, Mark T.; Fiel, Stanley B.; Foreman, Marilyn G.; Hanania, Nicola A.; Ireland, Belinda K.; Marchetti, Nathaniel; Marciniuk, Darcy D.; Mularski, Richard A.; Ornelas, Joseph; Stickland, Michael K.

    2015-01-01

    BACKGROUND: COPD is a major cause of morbidity and mortality in the United States as well as throughout the rest of the world. An exacerbation of COPD (periodic escalations of symptoms of cough, dyspnea, and sputum production) is a major contributor to worsening lung function, impairment in quality of life, need for urgent care or hospitalization, and cost of care in COPD. Research conducted over the past decade has contributed much to our current understanding of the pathogenesis and treatment of COPD. Additionally, an evolving literature has accumulated about the prevention of acute exacerbations. METHODS: In recognition of the importance of preventing exacerbations in patients with COPD, the American College of Chest Physicians (CHEST) and Canadian Thoracic Society (CTS) joint evidence-based guideline (AECOPD Guideline) was developed to provide a practical, clinically useful document to describe the current state of knowledge regarding the prevention of acute exacerbations according to major categories of prevention therapies. Three key clinical questions developed using the PICO (population, intervention, comparator, and outcome) format addressed the prevention of acute exacerbations of COPD: nonpharmacologic therapies, inhaled therapies, and oral therapies. We used recognized document evaluation tools to assess and choose the most appropriate studies and to extract meaningful data and grade the level of evidence to support the recommendations in each PICO question in a balanced and unbiased fashion. RESULTS: The AECOPD Guideline is unique not only for its topic, the prevention of acute exacerbations of COPD, but also for the first-in-kind partnership between two of the largest thoracic societies in North America. The CHEST Guidelines Oversight Committee in partnership with the CTS COPD Clinical Assembly launched this project with the objective that a systematic review and critical evaluation of the published literature by clinical experts and researchers in

  1. DNA-damage response associated with occupational exposure, age and chronic inflammation in workers in the automotive industry.

    Science.gov (United States)

    Savina, Natalya V; Smal, Marharyta P; Kuzhir, Tatyana D; Ershova-Pavlova, Alla A; Goncharova, Roza I

    2012-10-01

    The evaluation of genome integrity in populations occupationally exposed to combine industrial factors is of medical importance. In the present study, the DNA-damage response was estimated by means of the alkaline comet assay in a sizeable cohort of volunteers recruited among workers in the automotive industry. For this purpose, freshly collected lymphocytes were treated with hydrogen peroxide (100μM, 1min, 4°C) in vitro, and the levels of basal and H(2)O(2)-induced DNA damage, and the kinetics and efficiency of DNA repair were measured during a 180-min interval after exposure. The parameters studied in the total cohort of workers were in a range of values prescribed for healthy adult residents of Belarus. Based on the 95th percentiles, individuals possessing enhanced cellular sensitivity to DNA damage were present in different groups, but the frequency was significantly higher among elderly persons and among individuals with chronic inflammatory diseases. The results indicate that the inter-individual variations in DNA-damage response should be taken into account to estimate adequately the environmental genotoxic effects and to identify individuals with an enhanced DNA-damage response due to the influence of some external factors or intrinsic properties of the organism. Underling mechanisms need to be further explored. PMID:22772077

  2. 25-hydroxyvitamin D deficiency, exacerbation frequency and human rhinovirus exacerbations in chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Quint Jennifer K

    2012-06-01

    Full Text Available Abstract Background 25-hydroxyvitamin D deficiency is associated with COPD and increased susceptibility to infection in the general population. Methods We investigated whether COPD patients deficient in 25-hydroxyvitamin D were more likely to be frequent exacerbators, had reduced outdoor activity and were more susceptible to human rhinovirus (HRV exacerbations than those with insufficient and normal levels. We also investigated whether the frequency of FokI, BsmI and TaqIα 25-hydroxyvitamin D receptor (VDR polymorphisms differed between frequent and infrequent exacerbators. Results There was no difference in 25-hydroxyvitamin D levels between frequent and infrequent exacerbators in the summer; medians 44.1nmol/L (29.1 – 68.0 and 39.4nmol/L (22.3 – 59.2 or winter; medians 24.9nmol/L (14.3 – 43.1 and 27.1nmol/L (19.9 – 37.6. Patients who spent less time outdoors in the 14 days prior to sampling had lower 25-hydroxyvitamin D levels (p = 0.02. Day length was independently associated with 25-hydroxyvitamin D levels (p = 0.02. There was no difference in 25-hydroxyvitamin D levels between baseline and exacerbation; medians 36.2nmol/L (IQR 22.4-59.4 and 33.3nmol/L (23.0-49.7; p = 0.43. HRV positive exacerbations were not associated with lower 25-hydroxyvitamin D levels at exacerbation than exacerbations that did not test positive for HRV; medians 30.0nmol/L (20.4 – 57.8 and 30.6nmol/L (19.4 – 48.7. There was no relationship between exacerbation frequency and any VDR polymorphisms (all p > 0.05. Conclusions Low 25-hydroxyvitamin D levels in COPD are not associated with frequent exacerbations and do not increase susceptibility to HRV exacerbations. Independent of day length, patients who spend less time outdoors have lower 25-hydroxyvitamin D concentration.

  3. Damage to Liver and Skeletal Muscles in Marathon Runners During a 100 km Run With Regard to Age and Running Speed

    Directory of Open Access Journals (Sweden)

    Jastrzębski Zbigniew

    2015-03-01

    Full Text Available The purpose of this study was to determine: (1 whether damage to liver and skeletal muscles occurs during a 100 km run; (2 whether the metabolic response to extreme exertion is related to the age or running speed of the participant; (3 whether it is possible to determine the optimal running speed and distance for long-distance runners’ health by examining biochemical parameters in venous blood. Fourteen experienced male amateur ultra-marathon runners, divided into two age groups, took part in a 100 km run. Blood samples for liver and skeletal muscle damage indexes were collected from the ulnar vein just before the run, after 25, 50, 75 and 100 km, and 24 hours after termination of the run. A considerable increase in alanine aminotransferase (ALT and aspartate aminotransferase (AST was observed with the distance covered (p < 0.05, which continued during recovery. An increase in the mean values of lactate dehydrogenase (LDH, creatine kinase (CK and C-reactive protein (CRP (p < 0.05 was observed with each sequential course. The biggest differences between the age groups were found for the activity of liver enzymes and LDH after completing 75 km as well as after 24 hours of recovery. It can be concluded that the response to extreme exertion deteriorates with age in terms of the active movement apparatus.

  4. Nondestructive characterization of materials A growing demand for describing damage and service-life-relevant aging processes in plant components

    International Nuclear Information System (INIS)

    The nondestructive detection and characterization of damage to materials poses a challenge to instrumentation and inspection technology. A reliable method has yet to be developed anywhere in the world which is sufficiently rugged to be used on components in an industrial environment. The application-oriented studies conducted to date have demonstrated the complex overlapping of influences exerted on nondestructive measurement variables by the damage to be detected and by other material states and properties. The nondestructive detection and characterization of material damage will not offer any realistic chance of success until the material and component state is adequately characterized prior to the occurrence of the damage and variables are used which provide various types of information on the states and properties resulting from various interactions with the material. The process approaches and measurement techniques developed by the Institute for Nondestructive Testing are presented and evaluated below. The characterization of the initial state of a component with respect to its homogeneity and isotropy of its properties is possible by way of ultrasonic and magnetic techniques. Both techniques are also successfully employed in characterizing surface and bulk stress states in components. Adaptation of the sensor systems and material-specific preliminary testing are possibly required prior to actual application under practical conditions in individual cases. The same applies to the analysis of the anisotropy of material properties. Detecting areas of plastic deformation is possible via ultrasonic and magnetic techniques: quantification requires calibration, e.g. via a tensile test. (orig.)

  5. Changes in Cystic Fibrosis Airway Microbiota at Pulmonary Exacerbation

    OpenAIRE

    Carmody, Lisa A.; Zhao, Jiangchao; Schloss, Patrick D.; Petrosino, Joseph F; Murray, Susan; Young, Vincent B.; Li, Jun Z.; LiPuma, John J.

    2013-01-01

    Rationale: In persons with cystic fibrosis (CF), repeated exacerbations of pulmonary symptoms are associated with a progressive decline in lung function. Changes in the airway microbiota around the time of exacerbations are not well understood.

  6. Optimizing antibiotic selection in treating COPD exacerbations

    OpenAIRE

    Attiya Siddiqi; Sanjay Sethi

    2008-01-01

    Attiya Siddiqi, Sanjay SethiDivision of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Veterans Affairs Western New York Health Care System and University of Buffalo, State University of New York, Buffalo, New York, USAAbstract: Our understanding of the etiology, pathogenesis and consequences of acute exacerbations of chronic obstructive pulmonary disease (COPD) has increased substantially in the last decade. Several new lines of evidence demonstrate that bacterial isola...

  7. Wnt/β-catenin signaling induces the aging of mesenchymal stem cells through the DNA damage response and the p53/p21 pathway.

    Directory of Open Access Journals (Sweden)

    Da-yong Zhang

    Full Text Available Recent studies have demonstrated the importance of cellular extrinsic factors in the aging of adult stem cells. However, the effects of an aged cell-extrinsic environment on mesenchymal stem cell (MSC aging and the factors involved remain unclear. In the current study, we examine the effects of old rat serum (ORS on the aging of MSCs, and explore the effects and mechanisms of Wnt/β-catenin signaling on MSC aging induced by ORS treatment. Senescence-associated changes in the cells are examined with SA-β-galactosidase staining and ROS staining. The proliferation ability is detected by MTT assay. The surviving and apoptotic cells are determined using AO/EB staining. The results suggest that ORS promotes MSC senescence and reduces the proliferation and survival of cells. The immunofluorescence staining shows that the expression of β-catenin increases in MSCs of old rats. To identify the effects of Wnt/β-catenin signaling on MSC aging induced with ORS, the expression of β-catenin, GSK-3β, and c-myc are detected. The results show that the Wnt/β-catenin signaling in the cells is activated after ORS treatment. Then we examine the aging, proliferation, and survival of MSCs after modulating Wnt/β-catenin signaling. The results indicate that the senescence and dysfunction of MSCs in the medium containing ORS is reversed by the Wnt/β-catenin signaling inhibitor DKK1 or by β-catenin siRNA. Moreover, the expression of γ-H2A.X, a molecular marker of DNA damage response, p16(INK4a, p53, and p21 is increased in senescent MSCs induced with ORS, and is also reversed by DKK1 or by β-catenin siRNA. In summary, our study indicates the Wnt/β-catenin signaling may play a critical role in MSC aging induced by the serum of aged animals and suggests that the DNA damage response and p53/p21 pathway may be the main mediators of MSC aging induced by excessive activation of Wnt/β-catenin signaling.

  8. Virus Infection-Induced Bronchial Asthma Exacerbation

    Directory of Open Access Journals (Sweden)

    Mutsuo Yamaya

    2012-01-01

    Full Text Available Infection with respiratory viruses, including rhinoviruses, influenza virus, and respiratory syncytial virus, exacerbates asthma, which is associated with processes such as airway inflammation, airway hyperresponsiveness, and mucus hypersecretion. In patients with viral infections and with infection-induced asthma exacerbation, inflammatory mediators and substances, including interleukins (ILs, leukotrienes and histamine, have been identified in the airway secretions, serum, plasma, and urine. Viral infections induce an accumulation of inflammatory cells in the airway mucosa and submucosa, including neutrophils, lymphocytes and eosinophils. Viral infections also enhance the production of inflammatory mediators and substances in airway epithelial cells, mast cells, and other inflammatory cells, such as IL-1, IL-6, IL-8, GM-CSF, RANTES, histamine, and intercellular adhesion molecule-1. Viral infections affect the barrier function of the airway epithelial cells and vascular endothelial cells. Recent reports have demonstrated augmented viral production mediated by an impaired interferon response in the airway epithelial cells of asthma patients. Several drugs used for the treatment of bronchial asthma reduce viral and pro-inflammatory cytokine release from airway epithelial cells infected with viruses. Here, I review the literature on the pathogenesis of the viral infection-induced exacerbation of asthma and on the modulation of viral infection-induced airway inflammation.

  9. Treatment of pulmonary exacerbations in cystic fibrosis - could do better?

    Science.gov (United States)

    Smyth, Alan

    2016-08-01

    This article describes the nature and significance of pulmonary exacerbations in cystic fibrosis (CF). The effectiveness and safety of current exacerbation treatment are explored. The article concludes with a summary of clinical trials (completed and ongoing) which aim to improve the efficacy and safety of exacerbation treatment. PMID:27349725

  10. Amyloid beta, mitochondrial dysfunction and synaptic damage: implications for cognitive decline in aging and Alzheimer’s disease

    OpenAIRE

    Reddy, P. Hemachandra; Beal, M. Flint

    2008-01-01

    Recent studies of postmortem brains from Alzheimer’s disease (AD) patients and transgenic AD mice suggest that oxidative damage, induced by amyloid beta, is associated with mitochondria early in AD progression. Amyloid beta and amyloid precursor protein are known to localize to mitochondrial membranes, block the transport of nuclear-encoded mitochondrial proteins to mitochondria, interact with mitochondrial proteins, disrupt the electron transport chain, increase reactive oxygen species produ...

  11. Identification of aging and damage of neutron measurement probe of PRN system in Daya Bay nuclear power station

    International Nuclear Information System (INIS)

    The source range probe of RPN system in Daya Bay Nuclear Power Station is a boron-lined proportional counter. The middle range probe and the power range probe are boron-lined compensation ionization chambers. This paper introduces the relationship between different characteristic curves and aging of probes, and presents the way to identify the aging and malfunction of the neutron measurement probes in detail. For source range probe, if ΔC (aging extension of flat region in discrimative curve) > 60%, and the high voltage curve with aging trend by comparing with history curves, the probe has to be replaced. For middle range probe, the saturation curve of high voltage and electric current shall be drawn firstly, and then the coefficients P and V0 are established. When the curve changes greatly or V0 > 70 V, it means that the probe is becoming aging, and it is necessary to draw the saturation curves every 3 months in order to monitor the aging. If the curve changes continuously or V0 >140 V and P > 6%, the probe has to be replaced. For power range probe, when the curve changes greatly or V0 > 30 V, it means that the probe is becoming aging, and it is recommended to draw the saturation curves every 3 months. If the curve changes continuously or V0 > 60 V and P > 1.5%, the probe has to be replaced. (authors)

  12. Using bacterial biomarkers to identify early indicators of cystic fibrosis pulmonary exacerbation onset

    OpenAIRE

    Rogers, Geraint B.; Hoffman, Lucas R.; Johnson, Matt W; Mayer-Hamblett, Nicole; Schwarze, Jürgen; Carroll, Mary P; Bruce, Kenneth D.

    2011-01-01

    Acute periods of pulmonary exacerbation are the single most important cause of morbidity in cystic fibrosis patients, and may be associated with a loss of lung function. Intervening prior to the onset of a substantially increased inflammatory response may limit the associated damage to the airways. While a number of biomarker assays based on inflammatory markers have been developed, providing useful and important measures of disease during these periods, such factors are typically only elevat...

  13. The role of mean platelet volume predicting acute exacerbations of cystic fibrosis in children

    Directory of Open Access Journals (Sweden)

    Pinar Uysal

    2011-01-01

    Full Text Available Objective: The aim of this study is to evaluate the relationship between acute exacerbations and the mean platelet volume (MPV trend in children with cystic fibrosis (CF, to predict the exacerbations. Methods: A total of 46 children with CF and 37 healthy children were enrolled in the study. White blood cell count (WBC, hemoglobin level, platelet count, mean platelet volume (MPV, and mean corpuscular volume (MCV were retrospectively recorded. Results: Our study population consisted of 25 (54.3% males and 21 (45.7% females with CF and 20 (54.0% males and 17 (46.0% females in the healthy control group. The mean age of the CF patients was 6.32 ± 4.9 years and that of the healthy subjects was 7.02 ± 3.15 years. In the acute exacerbation period of CF, the MPV values were lower and WBC and platelet counts were higher than those in the healthy controls (P = 0.00, P = 0.00, P = 0.00, respectively. Besides, in acute exacerbation, the MPV values were lower and the WBC count was higher than the values in the non-exacerbation period (P 0= 0.01, P = 0.00, respectively. In the non-exacerbation period MPV was lower and platelet count was higher when compared to healthy subjects (P = 0.02, P = 0.04, respectively. Conclusion: This study suggests that MPV might be used as a simple, cost effective, diagnostic, predictive indicator for platelet activation in pediatric CF patients related to chronic inflammation, which might be helpful to discriminate or estimate exacerbations.

  14. The role of mean platelet volume predicting acute exacerbations of cystic fibrosis in children

    Science.gov (United States)

    Uysal, Pιnar; Tuncel, Tuba; Olmez, Duygu; Babayigit, Arzu; Karaman, Ozkan; Uzuner, Nevin

    2011-01-01

    OBJECTIVE: The aim of this study is to evaluate the relationship between acute exacerbations and the mean platelet volume (MPV) trend in children with cystic fibrosis (CF), to predict the exacerbations. METHODS: A total of 46 children with CF and 37 healthy children were enrolled in the study. White blood cell count (WBC), hemoglobin level, platelet count, mean platelet volume (MPV), and mean corpuscular volume (MCV) were retrospectively recorded. RESULTS: Our study population consisted of 25 (54.3%) males and 21 (45.7%) females with CF and 20 (54.0%) males and 17 (46.0%) females in the healthy control group. The mean age of the CF patients was 6.32 ± 4.9 years and that of the healthy subjects was 7.02 ± 3.15 years. In the acute exacerbation period of CF, the MPV values were lower and WBC and platelet counts were higher than those in the healthy controls (P = 0.00, P = 0.00, P = 0.00, respectively). Besides, in acute exacerbation, the MPV values were lower and the WBC count was higher than the values in the non-exacerbation period (P 0= 0.01, P = 0.00, respectively). In the non-exacerbation period MPV was lower and platelet count was higher when compared to healthy subjects (P = 0.02, P = 0.04, respectively). CONCLUSION: This study suggests that MPV might be used as a simple, cost effective, diagnostic, predictive indicator for platelet activation in pediatric CF patients related to chronic inflammation, which might be helpful to discriminate or estimate exacerbations. PMID:21977069

  15. COPD exacerbations associated with the modified Medical Research Council scale and COPD assessment test among Humana Medicare members

    Directory of Open Access Journals (Sweden)

    Pasquale MK

    2016-01-01

    Full Text Available Margaret K Pasquale,1 Yihua Xu,1 Christine L Baker,2 Kelly H Zou,3 John G Teeter,4 Andrew M Renda,5 Cralen C Davis,1 Theodore C Lee,6 Joel Bobula2 1Comprehensive Health Insights, Inc., Humana Inc., Louisville, KY, 2Outcomes and Evidence, Global Health & Value, Pfizer Inc., 3Statistical Center for Outcomes, Real-World and Aggregate Data, Global Innovative Pharma Business, Pfizer Inc., New York, NY, 4Global Medical Development, Global Innovative Pharma Business, Pfizer Inc., Groton, CT, 5Retail Strategy & Execution, Humana Inc., Louisville, KY, 6Global Medical Affairs, Global Innovative Pharma Business, Pfizer Inc., New York, NY, USA Background: The Global initiative for chronic Obstructive Lung Disease guidelines recommend assessment of COPD severity, which includes symptomatology using the modified Medical Research Council (mMRC or COPD assessment test (CAT score in addition to the degree of airflow obstruction and exacerbation history. While there is great interest in incorporating symptomatology, little is known about how patient reported symptoms are associated with future exacerbations and exacerbation-related costs.Methods: The mMRC and CAT were mailed to a randomly selected sample of 4,000 Medicare members aged >40 years, diagnosed with COPD (≥2 encounters with International Classification of Dis­eases-9th Edition Clinical Modification: 491.xx, 492.xx, 496.xx, ≥30 days apart. The exacerbations and exacerbation-related costs were collected from claims data during 365-day post-survey after exclusion of members lost to follow-up or with cancer, organ transplant, or pregnancy. A logistic regression model estimated the predictive value of exacerbation history and symptomatology on exacerbations during follow-up, and a generalized linear model with log link and gamma distribution estimated the predictive value of exacerbation history and symptomatology on exacerbation-related costs.Results: Among a total of 1,159 members who returned the

  16. A Review and Meta-Analysis of Age-Based Stereotype Threat: Negative Stereotypes, Not Facts, Do the Damage

    OpenAIRE

    Lamont, Ruth A.; Swift, Hannah J.; Abrams, Dominic

    2015-01-01

    Stereotype threat effects arise when an individual feels at risk of confirming a negative stereotype about their group and consequently underperforms on stereotype relevant tasks (Steele, 2010). Among older people, underperformance across cognitive and physical tasks is hypothesized to result from age-based stereotype threat (ABST) because of negative age-stereotypes regarding older adults’ competence. The present review and meta-analyses examine 22 published and 10 unpublished articles, incl...

  17. Histomorphological and histomorphometrical investigations of early bone damage following incorporation of optimal carcinogenic doses of 239-plutonium in male rats of different age

    International Nuclear Information System (INIS)

    There is early damage to bone at small carcinogenic amounts of the nuclide, including heavy defects of bone structure and bone marrow osteoporotic features of trabecular bone and only histomorphometrically detectable changes in bone metabolism. The dependence of radiation dose to skeleton and the spacial distribution of the nuclide on age and growth of the experimental animals is demonstrated and correlated to the histological findings. It is also shown that growth and metabolism parameters of bone influence the decorporation performance of the chelating agent Zn-DTPA. (orig.)

  18. A botanical containing freeze dried açai pulp promotes healthy aging and reduces oxidative damage in sod1 knockdown flies

    OpenAIRE

    Laslo, Mara; Sun, Xiaoping; Hsiao, Cheng-Te; Wu, Wells W.; Shen, Rong-Fong; Zou, Sige

    2012-01-01

    Superoxide dismutase 1 (SOD1), a critical enzyme against oxidative stress, is implicated in aging and degenerative diseases. We previously showed that a nutraceutical containing freeze-dried açai pulp promotes survival of flies fed a high-fat diet or sod1 knockdown flies fed a standard diet. Here, we investigated the effect of açai supplementation initiated at the early or late young adulthood on lifespan, physiological function, and oxidative damage in sod1 knockdown flies. We found that Aça...

  19. Low doses of ionizing radiation suppress an increase of spontaneous level of cytogenetic damage during aging of an organism (effect of genome stabilization)

    International Nuclear Information System (INIS)

    Effect of single γ-radiation (60Co) at the 0.1 and 0.2 Gy doses/dose rate - 0.125 Gy/min) on the accumulation of spontaneous cytogenetic damages in male mice of two-month-old during life time is studied. Results obtained show that low doses of ionizing radiation suppress the cytogenetic violations level growth stipulated by aging down to the level lower that spontaneous one, that is make the body to possess elevated genome stability

  20. Acute Exacerbations in COPD and their Control with Oral Immunisation with nontypeable Haemophilus influenzae

    Directory of Open Access Journals (Sweden)

    Robert eClancy

    2011-03-01

    Full Text Available Chronic obstructive pulmonary disease (COPD a term based on the demonstration of irreversible airways obstruction, introduced to unify a range of chronic progressive diseases of the airways consequent upon inhalation of toxins. While disease is initiated and progressed by inhaled toxins, an additional pathway of damage has emerged, with particular relevance to acute exacerbations. Exacerbations of disease due to an increase in the level of intra-bronchial inflammation have taken on a new significance as their role in determining both acute and chronic outcomes is better understood. This ‘second pathway’ of disease is a consequence of bacterial colonisation of damaged airways. Although bacteria have been linked to acute episodes in COPD over 50 years, only recently has quality data on antibiotic usage and the detection of ‘exacerbation isolates’ of non-typeable Haemophilus influenzae (NTHi provided strong argument in support of a pathogenic role. Yet a poor correlation between detection of colonising bacteria and clinical status remained a concern in attempts to explain a role for bacteria in a classical infection model. This presentation discusses a hypothesis that acute exacerbations reflect a T-cell dependent hypersensitivity response to colonising bacteria, with IL-17 dependent accumulation of neutrophils within the bronchus, as the main outcome measure. Critical protection against exacerbations following oral administration of NTHi, an immunotherapy that drives a TH17 Tcell response from Peyer’s patches, reduces the load of intrabronchial bacteria while preventing access of inhaled bacteria into small airways. Immunotherapy augments a physiological ‘loop’ based on aspiration of bronchus content into the gut. A second ‘hypersensitivity’ mechanism may cause bronchospasm – in both COPD and treatment-resistant asthma – due to specific IgE antibody directed against colonising bacteria, as oral NTHi abrogates wheeze in

  1. Nifedipine, a calcium channel blocker, inhibits advanced glycation end product (AGE)-elicited mesangial cell damage by suppressing AGE receptor (RAGE) expression via peroxisome proliferator-activated receptor-gamma activation

    International Nuclear Information System (INIS)

    The interaction between advanced glycation end products (AGE) and their receptor RAGE mediates the progressive alteration in renal architecture and loss of renal function in diabetic nephropathy. Oxidative stress generation and inflammation also play a central role in diabetic nephropathy. This study investigated whether and how nifedipine, a calcium channel blocker (CCB), blocked the AGE-elicited mesangial cell damage in vitro. Nifedipine, but not amlodipine, a control CCB, down-regulated RAGE mRNA levels and subsequently reduced reactive oxygen species (ROS) generation in AGE-exposed mesangial cells. AGE increased mRNA levels of vascular cell adhesion molecule-1 (VCAM-1) and induced monocyte chemoattractant protein-1 (MCP-1) production in mesangial cells, both of which were prevented by the treatment with nifedipine, but not amlodipine. The beneficial effects of nifedipine on AGE-exposed mesangial cells were blocked by the simultaneous treatment of GW9662, an inhibitor of peroxisome proliferator-activated receptor-γ (PPAR-γ). Although nifedipine did not affect expression levels of PPAR-γ, it increased the PPAR-γ transcriptional activity in mesangial cells. Our present study provides a unique beneficial aspect of nifedipine on diabetic nephropathy; it could work as an anti-inflammatory agent against AGE by suppressing RAGE expression in cultured mesangial cells via PPAR-γ activation.

  2. Nifedipine, a calcium channel blocker, inhibits advanced glycation end product (AGE)-elicited mesangial cell damage by suppressing AGE receptor (RAGE) expression via peroxisome proliferator-activated receptor-gamma activation

    Energy Technology Data Exchange (ETDEWEB)

    Matsui, Takanori [Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011 (Japan); Yamagishi, Sho-ichi, E-mail: shoichi@med.kurume-u.ac.jp [Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011 (Japan); Takeuchi, Masayoshi [Department of Pathophysiological Science, Faculty of Pharmaceutical Science, Hokuriku University, Kanazawa (Japan); Ueda, Seiji; Fukami, Kei; Okuda, Seiya [Department of Medicine, Kurume University School of Medicine, Kurume (Japan)

    2009-07-24

    The interaction between advanced glycation end products (AGE) and their receptor RAGE mediates the progressive alteration in renal architecture and loss of renal function in diabetic nephropathy. Oxidative stress generation and inflammation also play a central role in diabetic nephropathy. This study investigated whether and how nifedipine, a calcium channel blocker (CCB), blocked the AGE-elicited mesangial cell damage in vitro. Nifedipine, but not amlodipine, a control CCB, down-regulated RAGE mRNA levels and subsequently reduced reactive oxygen species (ROS) generation in AGE-exposed mesangial cells. AGE increased mRNA levels of vascular cell adhesion molecule-1 (VCAM-1) and induced monocyte chemoattractant protein-1 (MCP-1) production in mesangial cells, both of which were prevented by the treatment with nifedipine, but not amlodipine. The beneficial effects of nifedipine on AGE-exposed mesangial cells were blocked by the simultaneous treatment of GW9662, an inhibitor of peroxisome proliferator-activated receptor-{gamma} (PPAR-{gamma}). Although nifedipine did not affect expression levels of PPAR-{gamma}, it increased the PPAR-{gamma} transcriptional activity in mesangial cells. Our present study provides a unique beneficial aspect of nifedipine on diabetic nephropathy; it could work as an anti-inflammatory agent against AGE by suppressing RAGE expression in cultured mesangial cells via PPAR-{gamma} activation.

  3. Nondestructive characterization of materials. An increasingly requested demand to describe damages and lifetime relevant aging processes in plant components

    International Nuclear Information System (INIS)

    The procedural set-ups and measuring techniques developed at the IzfP are introduced and assessed. It is possible to characterize the initial state of a component regarding homogeneity and isotropy of its properties by means of ultrasonic and magnetic methods. Both methods are also used successfully to determine surface and volume stress states in components. For individual use it may be necessary to adapt the sensors and perform material specific preliminary studies. This applies also to the analysis of directionalities of material properties. Areas of plastic deformation can be detected by means of ultrasonic and magnetic methods; quantification, however, requires calibration, e.g. in tensile tests. In comparison, the positron annihilation process, at present exclusively applicable on a laboratory scale, has the advantage of being free, to a large extent, from internal stress. Detection and determination of creep damages is not yet possible with the necessary detection sensitivity. The potential of ultrasonic and magnetic methods for early detection of damages, i.e. reliable detection of increased porosity, is limited. (orig.)

  4. Choice of Cell Source in Cell-Based Therapies for Retinal Damage due to Age-Related Macular Degeneration: A Review

    Directory of Open Access Journals (Sweden)

    Sudhakar John

    2013-01-01

    Full Text Available Background. Age-related macular degeneration (AMD is a complex disorder that affects primarily the macula involving the retinal pigment epithelium (RPE but also to a certain extent the photoreceptor layer and the retinal neurons. Cell transplantation is a promising option for AMD and clinical trials are underway using different cell types. Methods. We hypothesize that instead of focusing on a particular cell source for concurrent regeneration of all the retinal layers and also to prevent exhaustive research on an array of cell sources for regeneration of each layer, the choice should depend on, precisely, which layer is damaged. Results. Thus, for a damage limited to the retinal pigment epithelial (RPE layer, the choice we suggest would be RPE cells. When the damage extends to rods and cones, the choice would be bone marrow stem cells and when retinal neurons are involved, relatively immature stem cell populations with an inherent capacity to yield neuronal lineage such as hematopoietic stem cells, embryonic stem cells, or induced pluripotent stem cells can be tried. Conclusion. This short review will prove to be a valuable guideline for those working on cell therapy for AMD to plan their future directions of research and therapy for this condition.

  5. [Peloid therapy in the complex sanatorium treatment of children of early age with complications of perinatal brain damage].

    Science.gov (United States)

    Ponomareva, S O; Babina, L M

    2003-01-01

    The search for novel approaches to multimodality prophylaxis and treatment of sequelae of perinatal nervous system affection as well as introduction of the early diagnostic criteria are topical problems in present-day pediatric neurology. Peloid therapy efficacy in combined sanatorium treatment was studied (Peloterm unit) in 44 infants aged 1 to 3 years. They suffered from sequelae of perinatal affections of the central nervous system including infantile cerebral paralysis. A positive effect (improvement of motor and psychic-speech development) was achieved in 98% cases. This indicates validity of this method in the treatment of CNS affections following perinatal affection of the brain in infants over 1 year of age. PMID:14753007

  6. Influence of aging and long-term caloric restriction on oxygen radical generation and oxidative DNA damage in rat liver mitochondria.

    Science.gov (United States)

    López-Torres, Mónica; Gredilla, Ricardo; Sanz, Alberto; Barja, Gustavo

    2002-05-01

    The effect of long-term caloric restriction and aging on the rates of mitochondrial H2O2 production and oxygen consumption as well as on oxidative damage to nuclear (nDNA) and mitochondrial DNA (mtDNA) was studied in rat liver tissue. Long-term caloric restriction significantly decreased H2O2 production of rat liver mitochondria (47% reduction) and significantly reduced oxidative damage to mtDNA (46% reduction) with no changes in nDNA. The decrease in ROS production was located at complex I because it only took place with complex I-linked substrates (pyruvate/malate) but not with complex II-linked substrates (succinate). The mechanism responsible for that decrease in ROS production was not a decrease in mitochondrial oxygen consumption because it did not change after long-term restriction. Instead, the caloric restricted mitochondria released less ROS per unit electron flow, due to a decrease in the reduction degree of the complex I generator. On the other hand, increased ROS production with aging in state 3 was observed in succinate-supplemented mitochondria because old control animals were unable to suppress H2O2 production during the energy transition from state 4 to state 3. The levels of 8-oxodG in mtDNA increased with age in old animals and this increase was abolished by caloric restriction. These results support the idea that caloric restriction reduces the aging rate at least in part by decreasing the rate of mitochondrial ROS production and so, the rate of oxidative attack to biological macromolecules like mtDNA. PMID:11978489

  7. Prediction of exacerbation chronic bronchopulmonary diseases in children with influenza

    Directory of Open Access Journals (Sweden)

    O. I. Afanaseva

    2015-01-01

    Full Text Available The objective: To develop a method for predicting exacerbation of chronic illness in children with asthma and cystic fibrosis, patients with influenza, based on the study of the dynamics of cytokines. Materials and methods: Were examined 52 patients with bronchial asthma and 45 children with cystic fibrosis at the age from 1 year to 12 years, located in infectious pulmonary Department at the planned treatment of underlying pathology, in which influenza was in-hospital infection. Control group observations included 40 patients with the flu, without concomitant pulmonary disease. The etiology of viral infection was established by detection of viral RNA in nasopharyngeal swabs by PCR. Among the influenza viruses were identified influenza АH1N1, АH3N2, influenza B, and in 2009–2010 the predominant antigen was the pandemic influenza virus АH1N1pdm09. Determination of the concentration of serum interleukins IL-1β, IL-4, IL-8, IL-10, ТNF-α, IFN-γ was performed in the 1st and 3rd day of hospitalization cytokines by the solid-phase immune-enzyme assay. Analysis of the results performed using statistical package SPSS 17.0 EN for Windows. Results: The flu caused the aggravation associated bronchopulmonary pathology in 2/3 of children, as MV patients, and patients with BA (65,4%-66,7%, respectively. With an increase of the ratio of IL-4 / IFN-γ and IL-10/IFN-γ, at least 5-6 times, influenza can be considered a trigger of exacerbation of chronic bronchopulmonary pathologies that require amplification of the therapy of bronchial asthma and of сystic fibrosis. The growth of prognostic coefficients in 2-3 times allows using for treatment of influenza in these patients only antiviral agents. Conclusion: The study has shown a method for predicting exacerbation of bronchial asthma and cystic fibrosis in children at an early stage of influenza by calculating the ratio of IL-4/IFN-γ and IL-10/IFN-γ in children aged from 1 year to 12 years. 

  8. Soluble CD93 as a Novel Biomarker in Asthma Exacerbation.

    Science.gov (United States)

    Sigari, Naseh; Jalili, Ali; Mahdawi, Laili; Ghaderi, Ebrahim; Shilan, Mohammadi

    2016-09-01

    Asthma research is shifting from studying symptoms and lung functions to the narrow-focus cellular profiles protein analysis, biomarkers, and genetic markers. The transmembrane glycoprotein CD93 is involved in endothelial cell migration, angiogenesis, leukocytes extravasation, apoptosis, innate immunity and inflammation. Relationships between the serum level of soluble CD93 (sCD93) and acute myocardial infarction/premature MI/inflammatory arthritis/skin sclerosis have recently been reported. We hypothesized that sCD93 would be elevated during the acute phase of asthma. We measured the serum level of sCD93 in 57 patients with asthma exacerbation and 57 age-and gender-matched healthy controls. Additionally, sCD93 was reassessed at the time of discharge from the hospital. Clinical characteristics and peak expiratory flow (PEF) of the patients were assessed. The primary outcome was the comparison of serum level of sCD93 between asthmatics and healthy subjects. The sCD93 values ranged from 128 to 789 ng/mL in asthmatics (345.83±115.81) and from 31 to 289 ng/mL in control subjects (169.46±62.43). The difference between the 2 groups was statistically significant (P<0.001). The association between sCD93 and asthma remained significant after adjusting for age, sex, and BMI. The differences between asthmatics and controls remained significant on the last day of hospital stay. The association between sCD93 and PEF was not significant. In conclusion, the serum level of soluble CD93 is increased in patients with asthma exacerbation. It also showed that serum levels of sCD93 decreased with treatment of asthma attack. The clinical usefulness of determination of sCD93 as a biomarker of asthma requires further studies. PMID:27334785

  9. Impaired Arterial Elasticity Identified by Pulse Waveform Analysis as a Marker for Vascular Wall Damage in Humans With Aging and Hypertension

    Institute of Scientific and Technical Information of China (English)

    Wang Yan; Tao Jun; Tu Chang; Yang Zhen; Xu Mingguo; Wang Jiemei; Jin Yafei; Ma Hong

    2005-01-01

    Objectives Cardiovascular risk factors lead to pathogenesis of atherosclerosis and its clinical events by impairing vascular wall. Endothelial dysfunction is the earliest marker for vascular wall injuries. Development of new method to detect early vascular wall damage has an important clinical implication for the prevention and treatment of cardiovascular diseases. Therefore, the present study was performed to evaluate effect of aging and hypertension, two independent risk factors for cardiovascular diseases, on arterial elasticity by using pulse waveform analysis and investigate whether the changes in arterial elasticity can be used as a risk marker for vascular structural and functional abnormalities. Methods Using modified Windkessel model of the circulation and pulse waveform analysis,C 1 large artery and C2 small artery elasticity indices of 204 Chinese normal healthy subjects ( age 15-80years) and 46 Chinese essential hypertensive patients (age 35-70 years) were measured. Age- and hypertension-related arterial elasticity changes were examined. Results C1 large artery and C2 small artery elasticity indices were reduced with advancing age in healthy subjects. C1 large artery and C2 small artery elasticity indices were negatively correlated with age (r=-0.628, P<0.001; r=-0.595, P<0.001). C1 large artery and C2 small artery elasticity indices in patients with essential hypertension compared with the agematched healthy subjects were (9.31±3.85 ml/mm Hg x 10 versus 15.13±4.14 ml/mmHg x 10, P<0.001) and (3.57± 1.62 ml/mm Hg x 100 versus 7.89±2.91 ml/mmHg ×100 P <0.001), respectively, and were significantly lower than the corresponding healthy subjects. There were negative association between C1large artery and C2 small artery elasticity indices and systolic blood pressure (r=-0.37, P<0.05; r=-0.39,P<0.05) and pulse pressure (r=-0.39, P<0.05; r=0.43,P<0.05) in patients with essential hypertension.Conclusions Advancing age and essential

  10. Shedding Light on Copyright Trolls: An Analysis of Mass Copyright Litigation in the Age of Statutory Damages

    OpenAIRE

    DeBriyn, James

    2012-01-01

    Copyright law and the Internet are at an impasse. The looming question is how to approach unlicensed distribution of copyrighted works in the age of peer-to-peer networks. To supplement profits from copyrighted works, copyright holders have devised a mass-litigation model to monetize, rather than deter, infringement. Because of the ...

  11. CMTR1 is associated with increased asthma exacerbations in patients taking inhaled corticosteroids.

    Science.gov (United States)

    Dahlin, Amber; Denny, Joshua; Roden, Dan M; Brilliant, Murray H; Ingram, Christie; Kitchner, Terrie E; Linneman, James G; Shaffer, Christian M; Weeke, Peter; Xu, Hua; Kubo, Michiaki; Tamari, Mayumi; Clemmer, George L; Ziniti, John; McGeachie, Michael J; Tantisira, Kelan G; Weiss, Scott T; Wu, Ann Chen

    2015-12-01

    Inhaled corticosteroids (ICS) are the most effective controller medications for asthma, and variability in ICS response is associated with genetic variation. Despite ICS treatment, some patients with poor asthma control experience severe asthma exacerbations, defined as a hospitalization or emergency room visit. We hypothesized that some individuals may be at increased risk of asthma exacerbations, despite ICS use, due to genetic factors. A GWAS of 237,726 common, independent markers was conducted in 806 Caucasian asthmatic patients from two population-based biobanks: BioVU, at Vanderbilt University Medical Center (VUMC) in Tennessee (369 patients), and Personalized Medicine Research Project (PMRP) at the Marshfield Clinic in Wisconsin (437 patients). Using a case-control study design, the association of each SNP locus with the outcome of asthma exacerbations (defined as asthma-related emergency department visits or hospitalizations concurrent with oral corticosteroid use), was evaluated for each population by logistic regression analysis, adjusting for age, gender and the first four principal components. A meta-analysis of the results was conducted. Validation of expression of selected candidate genes was determined by evaluating an independent microarray expression data set. Our study identified six novel SNPs associated with differential risk of asthma exacerbations (P < 10(-05)). The top GWAS result, rs2395672 in CMTR1, was associated with an increased risk of exacerbations in both populations (OR = 1.07, 95% CI 1.03-1.11; joint P = 2.3 × 10(-06)). Two SNPs (rs2395672 and rs279728) were associated with increased risk of exacerbations, while the remaining four SNPs (rs4271056, rs6467778, rs2691529, and rs9303988) were associated with decreased risk. Three SNPs (rs2395672, rs6467778, and rs2691529) were present in three genes: CMTR1, TRIM24 and MAGI2. The CMTR1 mRNA transcript was significantly differentially expressed in nasal lavage samples

  12. Toll-like receptor 2 deficiency leads to delayed exacerbation of ischemic injury

    Directory of Open Access Journals (Sweden)

    Bohacek Ivan

    2012-08-01

    Full Text Available Abstract Background Using a live imaging approach, we have previously shown that microglia activation after stroke is characterized by marked and long-term induction of the Toll-like receptor (TLR 2 biophotonic signals. However, the role of TLR2 (and potentially other TLRs beyond the acute innate immune response and as early neuroprotection against ischemic injury is not well understood. Methods TLR2−/− mice were subjected to transient middle cerebral artery occlusion followed by different reperfusion times. Analyses assessing microglial activation profile/innate immune response were performed using in situ hybridization, immunohistochemistry analysis, flow cytometry and inflammatory cytokine array. The effects of the TLR2 deficiency on the evolution of ischemic brain injury were analyzed using a cresyl violet staining of brain sections with appropriate lesion size estimation. Results Here we report that TLR2 deficiency markedly affects post-stroke immune response resulting in delayed exacerbation of the ischemic injury. The temporal analysis of the microglia/macrophage activation profiles in TLR2−/− mice and age-matched controls revealed reduced microglia/macrophage activation after stroke, reduced capacity of resident microglia to proliferate as well as decreased levels of monocyte chemotactic protein-1 (MCP-1 and consequently lower levels of CD45high/CD11b+ expressing cells as shown by flow cytometry analysis. Importantly, although acute ischemic lesions (24 to 72 h were smaller in TLR2−/− mice, the observed alterations in innate immune response were more pronounced at later time points (at day 7 after initial stroke, which finally resulted in delayed exacerbation of ischemic lesion leading to larger chronic infarctions as compared with wild-type mice. Moreover, our results revealed that TLR2 deficiency is associated with significant decrease in the levels of neurotrophic/anti-apoptotic factor Insulin-like growth factor-1 (IGF-1

  13. Relationship of asthma management, socioeconomic status, and medication insurance characteristics to exacerbation frequency in children with asthma

    Science.gov (United States)

    Ungar, Wendy J.; Paterson, J. Michael; Gomes, Tara; Bikangaga, Peter; Gold, Milton; To, Teresa; Kozyrskyj, Anita L.

    2016-01-01

    Background Less than 25% of asthmatic children are well controlled. Objective To identify factors associated with asthma exacerbation causing emergency department (ED) visits or hospitalizations related to health status, socioeconomic status (SES), and drug insurance. Methods In this retrospective cohort study, complete data were collected on 490 asthmatic children regarding demographics, SES, drug plan characteristics, health status, health resource use, and symptoms. Interview data were linked to administrative data on asthma ED visits and hospitalizations occurring in the following year. Multiple Poisson regression identified independent variables associated with ED visits or hospitalizations in the full cohort and in a subgroup with prescription drug insurance. Results Younger age, previous emergency visits, nebulizer use, pet ownership, and receipt of asthma education but not an action plan were significantly associated with more frequent exacerbations. In the full cohort, children with high income adequacy had 28% fewer exacerbations than did children with low income adequacy. In the subgroup with drug insurance, girls had 26% fewer exacerbations than did boys, and children with food, drug, or insect allergies had 52% more exacerbations than did children without allergies. Children of families with annual insurance deductibles greater than $90 had 95% fewer exacerbations. Every percentage increase in the proportion of income spent out-of-pocket on asthma medications was associated with a 14% increase in exacerbations. Conclusions Asthma history, disease management factors, and SES were associated with exacerbations requiring urgent care. In families with drug plans, the magnitude of asthma medication cost-sharing as a proportion of household income, rather than income alone, was significantly associated with exacerbations. PMID:21195940

  14. Impact of exacerbations on health care cost and resource utilization in chronic obstructive pulmonary disease patients with chronic bronchitis from a predominantly Medicare population

    Directory of Open Access Journals (Sweden)

    Pasquale MK

    2012-11-01

    Full Text Available Margaret K Pasquale,1 Shawn X Sun,2 Frank Song,1 Heather J Hartnett,1 Stephen A Stemkowski11Competitive Health Analytics, Louisville, KY, USA; 2Health Economics and Outcomes Research, Forest Research Institute, Jersey City, NJ, USABackground: Exacerbations of chronic obstructive pulmonary disease (COPD lead to significant increases in resource utilization and cost to the health care system. COPD patients with chronic bronchitis and a history of exacerbations pose an additional burden to the system. This study examined health care utilization and cost among these patients.Methods: For this retrospective analysis, data were extracted from a large national health plan with a predominantly Medicare population. This study involved patients who were aged 40–89 years, had been enrolled continuously for 24 months or more, had at least two separate insurance claims for COPD with chronic bronchitis (International Classification of Diseases, Ninth Revision, Clinical Modification code 491.xx, and had pharmacy claims for COPD maintenance medications between January 1, 2007, and March 31, 2009. Two years of data were examined for each patient; the index date was defined as the first occurrence of COPD. Baseline characteristics were obtained from the first year of data, with health outcomes tracked in the second year. Severe exacerbation was defined by COPD-related hospitalization or death; moderate exacerbation was defined by oral or parenteral corticosteroid use. Adjusted numbers of exacerbations and COPD-related costs per patient were estimated controlling for demographic and clinical characteristics.Results: The final study sample involved 8554 patients; mean age was 70.1 ± 8.6 years and 49.8% of the overall population had exacerbation, 13.9% had a severe exacerbation only, 29.1% had a moderate exacerbation only, and 6.8% had both a severe and moderate exacerbation. COPD-related mean annual costs were $4069 (all figures given in US dollars for the

  15. Burst strength behaviour of an aging subsea gas pipeline elbow in different external and internal corrosion-damaged positions

    Science.gov (United States)

    Lee, Geon Ho; Pouraria, Hassan; Seo, Jung Kwan; Paik, Jeom Kee

    2015-09-01

    Evaluation of the performance of aging structures is essential in the oil and gas industry, where the inaccurate prediction of structural performance can have significantly hazardous consequences. The effects of structure failure due to the significant reduction in wall thickness, which determines the burst strength, make it very complicated for pipeline operators to maintain pipeline serviceability. In other words, the serviceability of gas pipelines and elbows needs to be predicted and assessed to ensure that the burst or collapse strength capacities of the structures remain less than the maximum allowable operation pressure. In this study, several positions of the corrosion in a subsea elbow made of API X42 steel were evaluated using both design formulas and numerical analysis. The most hazardous corrosion position of the aging elbow was then determined to assess its serviceability. The results of this study are applicable to the operational and elbow serviceability needs of subsea pipelines and can help predict more accurate replacement or repair times.

  16. Characterisation and prevention of exacerbations in frequently exacerbating patienst with COPD

    NARCIS (Netherlands)

    S. Uzun (Sevim)

    2014-01-01

    markdownabstract__Abstract__ Chronic obstructive pulmonary disease (COPD) is a disease which is characterised by airway inflammation and progressive airflow limitation with poor reversibility. Periods of acute deterioration lie in the natural course of the disease and are called exacerbations. In l

  17. Genome Wide Association Study to predict severe asthma exacerbations in children using random forests classifiers

    Directory of Open Access Journals (Sweden)

    Litonjua Augusto A

    2011-06-01

    Full Text Available Abstract Background Personalized health-care promises tailored health-care solutions to individual patients based on their genetic background and/or environmental exposure history. To date, disease prediction has been based on a few environmental factors and/or single nucleotide polymorphisms (SNPs, while complex diseases are usually affected by many genetic and environmental factors with each factor contributing a small portion to the outcome. We hypothesized that the use of random forests classifiers to select SNPs would result in an improved predictive model of asthma exacerbations. We tested this hypothesis in a population of childhood asthmatics. Methods In this study, using emergency room visits or hospitalizations as the definition of a severe asthma exacerbation, we first identified a list of top Genome Wide Association Study (GWAS SNPs ranked by Random Forests (RF importance score for the CAMP (Childhood Asthma Management Program population of 127 exacerbation cases and 290 non-exacerbation controls. We predict severe asthma exacerbations using the top 10 to 320 SNPs together with age, sex, pre-bronchodilator FEV1 percentage predicted, and treatment group. Results Testing in an independent set of the CAMP population shows that severe asthma exacerbations can be predicted with an Area Under the Curve (AUC = 0.66 with 160-320 SNPs in comparison to an AUC score of 0.57 with 10 SNPs. Using the clinical traits alone yielded AUC score of 0.54, suggesting the phenotype is affected by genetic as well as environmental factors. Conclusions Our study shows that a random forests algorithm can effectively extract and use the information contained in a small number of samples. Random forests, and other machine learning tools, can be used with GWAS studies to integrate large numbers of predictors simultaneously.

  18. Behaviour and damage of aged austenitic-ferritic steels: a micro-mechanical approach; Comportement et endommagement des aciers austeno-ferritiques vieillis: une approche micromecanique

    Energy Technology Data Exchange (ETDEWEB)

    Bugat, St

    2000-12-15

    The austenitic-ferritic steels are used in the PWR primary cooling system. At the running temperature (320 C), they are submitted to a slow aging, which leads to the embrittlement of the ferritic phase. This embrittlement leads to a decrease of the mechanical properties, in particular of the crack resistance of the austenitic-ferritic steels. The damage and rupture of the austenitic-ferritic steels have been approached at the ENSMP by the works of P. Joly (1992) and of L. Devilliers-Guerville (1998). These works have allowed to reveal a damage heterogeneity which induces a strong dispersion on the ductilities and the toughnesses as well as on the scale effects. Modeling including the damage growth kinetics measured experimentally, have allowed to verify these effects. Nevertheless, they do not consider the two-phase character of the material and do not include a physical model of the cleavage cracks growth which appear in the embrittled ferrite. In this study, is proposed a description of the material allowing to treat these aspects while authorizing the structure calculation. In a first part, the material is studied. The use of the ESBD allows to specify the complex morphology of these steels and crystal orientation relations between the two phases. Moreover, it is shown that the two phases keep the same crystal orientation in the zones, called bicrystals, whose size varies between 500 {mu}m and 1 mm. The study of the sliding lines, coupled to the ESBD, allows to specify too the deformation modes of the two phases. At last, tensile and tensile-compression tests at various deformation range are carried out to characterize the macroscopic mechanical behaviour of these materials. Then, a micro-mechanical modeling of the material behaviour is proposed. This one takes into account the three scales identified at the preceding chapter. The first scale, corresponding to the laths is described as a monocrystal whose behaviour includes both an isotropic and a kinematic

  19. A review and meta-analysis of age-based stereotype threat: negative stereotypes, not facts, do the damage.

    Science.gov (United States)

    Lamont, Ruth A; Swift, Hannah J; Abrams, Dominic

    2015-03-01

    Stereotype threat effects arise when an individual feels at risk of confirming a negative stereotype about their group and consequently underperforms on stereotype relevant tasks (Steele, 2010). Among older people, underperformance across cognitive and physical tasks is hypothesized to result from age-based stereotype threat (ABST) because of negative age-stereotypes regarding older adults' competence. The present review and meta-analyses examine 22 published and 10 unpublished articles, including 82 effect sizes (N = 3882) investigating ABST on older people's (Mage = 69.5) performance. The analysis revealed a significant small-to-medium effect of ABST (d = .28) and important moderators of the effect size. Specifically, older adults are more vulnerable to ABST when (a) stereotype-based rather than fact-based manipulations are used (d = .52); (b) when performance is tested using cognitive measures (d = .36); and (c) occurs reliably when the dependent variable is measured proximally to the manipulation. The review raises important theoretical and methodological issues, and areas for future research. PMID:25621742

  20. Burst strength behaviour of an aging subsea gas pipeline elbow in different external and internal corrosion-damaged positions

    Directory of Open Access Journals (Sweden)

    Lee Geon Ho

    2015-05-01

    Full Text Available Evaluation of the performance of aging structures is essential in the oil and gas industry, where the inaccurate prediction of structural performance can have significantly hazardous consequences. The effects of structure failure due to the significant reduction in wall thickness, which determines the burst strength, make it very complicated for pipeline operators to maintain pipeline serviceability. In other words, the serviceability of gas pipelines and elbows needs to be predicted and assessed to ensure that the burst or collapse strength capacities of the structures remain less than the maximum allowable operation pressure. In this study, several positions of the corrosion in a subsea elbow made of API X42 steel were evaluated using both design formulas and numerical analysis. The most hazardous corrosion position of the aging elbow was then determined to assess its serviceability. The results of this study are applicable to the operational and elbow serviceability needs of subsea pipelines and can help predict more accurate replacement or repair times.

  1. Association of airborne Aspergillus with asthma exacerbation in Southern Pakistan

    OpenAIRE

    Zubairi, Ali Bin Sarwar; Azam, Iqbal; Awan, Safia; Zafar, Afia; Imam, Asif Ali

    2014-01-01

    Background Exposure to airborne fungi has been related with exacerbation of asthma in adults and children leading to increased outpatient, emergency room visits, and hospitalizations. Hypersensitivity to these airborne fungi may be an important initial predisposing factor in the development and exacerbation of asthma. Objective This study was conducted to determine an association between fungal types and spore concentrations with the risk of asthma exacerbation in adults. Methods This cross-s...

  2. How Diet Intervention via Modulation of DNA Damage Response through MicroRNAs May Have an Effect on Cancer Prevention and Aging, an in Silico Study.

    Science.gov (United States)

    Carotenuto, Felicia; Albertini, Maria C; Coletti, Dario; Vilmercati, Alessandra; Campanella, Luigi; Darzynkiewicz, Zbigniew; Teodori, Laura

    2016-01-01

    The DNA damage response (DDR) is a molecular mechanism that cells have evolved to sense DNA damage (DD) to promote DNA repair, or to lead to apoptosis, or cellular senescence if the damage is too extensive. Recent evidence indicates that microRNAs (miRs) play a critical role in the regulation of DDR. Dietary bioactive compounds through miRs may affect activity of numerous genes. Among the most studied bioactive compounds modulating expression of miRs are epi-gallocatechin-3-gallate, curcumin, resveratrol and n3-polyunsaturated fatty acids. To compare the impact of these dietary compounds on DD/DDR network modulation, we performed a literature search and an in silico analysis by the DIANA-mirPathv3 software. The in silico analysis allowed us to identify pathways shared by different miRs involved in DD/DDR vis-à-vis the specific compounds. The results demonstrate that certain miRs (e.g., -146, -21) play a central role in the interplay among DD/DDR and the bioactive compounds. Furthermore, some specific pathways, such as "fatty acids biosynthesis/metabolism", "extracellular matrix-receptor interaction" and "signaling regulating the pluripotency of stem cells", appear to be targeted by most miRs affected by the studied compounds. Since DD/DDR and these pathways are strongly related to aging and carcinogenesis, the present in silico results of our study suggest that monitoring the induction of specific miRs may provide the means to assess the antiaging and chemopreventive properties of particular dietary compounds. PMID:27213347

  3. How Diet Intervention via Modulation of DNA Damage Response through MicroRNAs May Have an Effect on Cancer Prevention and Aging, an in Silico Study

    Directory of Open Access Journals (Sweden)

    Felicia Carotenuto

    2016-05-01

    Full Text Available The DNA damage response (DDR is a molecular mechanism that cells have evolved to sense DNA damage (DD to promote DNA repair, or to lead to apoptosis, or cellular senescence if the damage is too extensive. Recent evidence indicates that microRNAs (miRs play a critical role in the regulation of DDR. Dietary bioactive compounds through miRs may affect activity of numerous genes. Among the most studied bioactive compounds modulating expression of miRs are epi-gallocatechin-3-gallate, curcumin, resveratrol and n3-polyunsaturated fatty acids. To compare the impact of these dietary compounds on DD/DDR network modulation, we performed a literature search and an in silico analysis by the DIANA-mirPathv3 software. The in silico analysis allowed us to identify pathways shared by different miRs involved in DD/DDR vis-à-vis the specific compounds. The results demonstrate that certain miRs (e.g., -146, -21 play a central role in the interplay among DD/DDR and the bioactive compounds. Furthermore, some specific pathways, such as “fatty acids biosynthesis/metabolism”, “extracellular matrix-receptor interaction” and “signaling regulating the pluripotency of stem cells”, appear to be targeted by most miRs affected by the studied compounds. Since DD/DDR and these pathways are strongly related to aging and carcinogenesis, the present in silico results of our study suggest that monitoring the induction of specific miRs may provide the means to assess the antiaging and chemopreventive properties of particular dietary compounds.

  4. Sun exposure and visual field damage among children on the Adriatic Island Rab--possible initial risk factor in development of age-related macular degeneration.

    Science.gov (United States)

    Vojniković, Bozidar; Micović, Vladimir; Coklo, Miran; Vojniković, Davor

    2009-09-01

    The Adriatic Island Rab, situated in the northern part of the Croatian sea, is more strongly exposed to sunlight (especially from May to October) than the other parts of Croatia and most of the European countries. As consequences of higher solar radiation, significant percentage of Pseudoexfoliation of lens capsula occurs in 15% and fundus picture of AMD (Age-Related Macular Degeneration) in 18% of agriculturalists and fishermen (45-70 years old). We previously presented the first clinical study showing that in AMD the peripheral visual field is also damaged. In this clinical study we examined 68 children (8-15 years old), including following procedures: vision correction, slit lamp examination, visual field in technic of isopters and profile quantitative perimetry (meridian retinal thresholds examination) using Kowa automated perimeter. In 15% of examinees we found strictly foveal "degeneration", and changes of visual fields: higher meridian thresholds and typical changes with invagination of isopters. It is very interesting that these children with damaged visual field and fundus picture do not protect their eyes from the sunlight during summertime. We suggest the possibility of the influence of higher sun radiation as one of the risk factors in the earlier development of future AMD. PMID:19860099

  5. COPD management costs according to the frequency of COPD exacerbations in UK primary care

    Directory of Open Access Journals (Sweden)

    Punekar YS

    2014-01-01

    Full Text Available Yogesh Suresh Punekar,1 Amit Shukla,2 Hana Müllerova31Global Health Outcomes, GlaxoSmithKline R&D, Uxbridge, UK; 2Worldwide Epidemiology, GlaxoSmithKline R&D, Upper Providence, PA, USA; 3Worldwide Epidemiology, GlaxoSmithKline R&D, Uxbridge, UKBackground: The economic burden of chronic obstructive pulmonary disease (COPD exacerbations is significant, but the impact of other sources on the overall cost of COPD management is largely unknown. We aimed to estimate overall costs for patients experiencing none, one, or two or more exacerbations per year in the UK.Methods: A retrospective cohort of prevalent COPD patients was identified in the Clinical Practice Research Datalink UK database. Patients with information recorded for at least 12 months before and after cohort entry date were included (first prevalent COPD diagnosis confirmed by spirometry on/after April 1, 2009. Patients were categorized as having none, one, or two or more moderate-to-severe COPD exacerbations in the 12 months after cohort entry and further classified by the Global initiative for chronic Obstructive Lung Disease (GOLD category of airflow obstruction and the Medical Research Council dyspnea scale. Study outcomes included counts of general practitioner interactions, moderate-severe COPD exacerbations, and non-COPD hospitalizations. Estimated resource use costs were calculated using National Health Service reference costs for 2010–2011.Results: The cohort comprised 58,589 patients (mean age 69.5 years, mean dyspnea grade 2.5, females 46.6%, current smokers 33.1%. The average total annual per patient cost of COPD management, excluding medications, was £2,108 for all patients and £1,523, £2,405, and £3,396 for patients experiencing no, one, or two or more moderate-to-severe exacerbations, respectively. General practitioner interactions contributed most to these annual costs, accounting for £1,062 (69.7%, £1,313 (54.6%, and £1,592 (46.9% in patients with no, one, or

  6. Superior neuroprotective effects of cerebrolysin in nanoparticle-induced exacerbation of hyperthermia-induced brain pathology.

    Science.gov (United States)

    Sharma, Aruna; Muresanu, Dafin Fior; Mössler, Herbert; Sharma, Hari Shanker

    2012-02-01

    In recent years, the incidence of heat stroke and associated brain pathology are increasing Worldwide. More than half of the world's population are living in areas associated with high environmental heat especially during the summer seasons. Thus, new research is needed using novel drug targets to achieve neuroprotection in heat-induced brain pathology. Previous research from our laboratory showed that the pathophysiology of brain injuries following heat stroke are exacerbated by chronic intoxication of engineered nanoparticles of small sizes (50-60 nm) following identical heat exposure in rats. Interestingly, in nanoparticle-intoxicated animals the known neuroprotective agents in standard doses failed to induce effective neuroprotection. This suggests that the dose-response of the drugs either requires modification or new therapeutic agents are needed to provide better neuroprotection in nanoparticle-intoxicated animals after heat stroke. This review is focused on the use of cerebrolysin, a mixture of several neurotrophic factors and active peptide fragments, in relation to other neuroprotective agents normally used to treat ischemic stroke in clinics in nanoparticle-induced exacerbation of brain damage in heat stroke. It appears that cerebrolysin exerts the most superior neuroprotective effects in heat stress as compared to other neuroprotective agents on brain pathology in normal rats. Interestingly, to induce effective neuroprotection in nanoparticle-induced exacerbation of brain pathology a double dose of cerebrolysin is needed. On the other hand, double doses of the other drugs were quite ineffective in reducing brain damage. These observations suggest that the drug type and doses are important factors in attenuating nanoparticle-induced exacerbation of brain pathology in heat stroke. The functional significance and possible mechanisms of drug-induced neuroprotection in nanoparticle-treated, heat-stressed rats are discussed. PMID:22229316

  7. Mitochondrial iron accumulation exacerbates hepatic toxicity caused by hepatitis C virus core protein

    International Nuclear Information System (INIS)

    Patients with long-lasting hepatitis C virus (HCV) infection are at major risk of hepatocellular carcinoma (HCC). Iron accumulation in the livers of these patients is thought to exacerbate conditions of oxidative stress. Transgenic mice that express the HCV core protein develop HCC after the steatosis stage and produce an excess of hepatic reactive oxygen species (ROS). The overproduction of ROS in the liver is the net result of HCV core protein-induced dysfunction of the mitochondrial respiratory chain. This study examined the impact of ferric nitrilacetic acid (Fe-NTA)-mediated iron overload on mitochondrial damage and ROS production in HCV core protein-expressing HepG2 (human HCC) cells (Hep39b cells). A decrease in mitochondrial membrane potential and ROS production were observed following Fe-NTA treatment. After continuous exposure to Fe-NTA for six days, cell toxicity was observed in Hep39b cells, but not in mock (vector-transfected) HepG2 cells. Moreover, mitochondrial iron (59Fe) uptake was increased in the livers of HCV core protein-expressing transgenic mice. This increase in mitochondrial iron uptake was inhibited by Ru360, a mitochondrial Ca2+ uniporter inhibitor. Furthermore, the Fe-NTA-induced augmentation of mitochondrial dysfunction, ROS production, and cell toxicity were also inhibited by Ru360 in Hep39b cells. Taken together, these results indicate that Ca2+ uniporter-mediated mitochondrial accumulation of iron exacerbates hepatocyte toxicity caused by the HCV core protein. - Highlights: • Iron accumulation in the livers of patients with hepatitis C virus (HCV) infection is thought to exacerbate oxidative stress. • The impact of iron overload on mitochondrial damage and ROS production in HCV core protein-expressing cells were examined. • Mitochondrial iron uptake was increased in the livers of HCV core protein-expressing transgenic mice. • Ca2+ uniporter-mediated mitochondrial accumulation of iron exacerbates hepatocyte toxicity caused by

  8. Metformin in severe exacerbations of chronic obstructive pulmonary disease: a randomised controlled trial

    Science.gov (United States)

    Hitchings, Andrew W; Lai, Dilys; Jones, Paul W; Baker, Emma H

    2016-01-01

    Background Severe exacerbations of COPD are commonly associated with hyperglycaemia, which predicts adverse outcomes. Metformin is a well-established anti-hyperglycaemic agent in diabetes mellitus, possibly augmented with anti-inflammatory effects, but its effects in COPD are unknown. We investigated accelerated metformin therapy in severe COPD exacerbations, primarily to confirm or refute an anti-hyperglycaemic effect, and secondarily to explore its effects on inflammation and clinical outcome. Methods This was a multicentre, randomised, double-blind, placebo-controlled trial testing accelerated metformin therapy in non-diabetic patients, aged ≥35 years, hospitalised for COPD exacerbations. Participants were assigned in a 2:1 ratio to 1 month of metformin therapy, escalated rapidly to 2 g/day, or matched placebo. The primary end point was mean in-hospital blood glucose concentration. Secondary end points included the concentrations of fructosamine and C reactive protein (CRP), and scores on the COPD Assessment Test and Exacerbations of Chronic Pulmonary Disease Tool. Results 52 participants (mean (±SD) age 67±9 years) were randomised (34 to metformin, 18 to placebo). All were included in the primary end point analysis. The mean blood glucose concentrations in the metformin and placebo groups were 7.1±0.9 and 8.0±3.3 mmol/L, respectively (difference −0.9 mmol/L, 95% CI −2.1 to +0.3; p=0.273). No significant between-group differences were observed on any of the secondary end points. Adverse reactions, particularly gastrointestinal effects, were more common in metformin-treated participants. Conclusion Metformin did not ameliorate elevations in blood glucose concentration among non-diabetic patients admitted to hospital for COPD exacerbations, and had no detectable effect on CRP or clinical outcomes. Trial registration number ISRCTN66148745 and NCT01247870. PMID:26917577

  9. Incidence and risk factors for exacerbations of asthma during pregnancy

    Directory of Open Access Journals (Sweden)

    Ali Z

    2013-05-01

    Full Text Available Zarqa Ali, Charlotte Suppli UlrikDepartment of Pulmonary Medicine, Hvidovre Hospital and University of Copenhagen, Copenhagen, DenmarkBackground: Asthma is one of the most common chronic diseases among pregnant women. Acute exacerbations of asthma during pregnancy have an unfavorable impact on pregnancy outcome. This review provides an overview of current knowledge of incidence, mechanisms, and risk factors for acute exacerbations of asthma during pregnancy.Methods: A narrative literature review was carried out using the PubMed database.Results: During pregnancy, up to 6% of women with asthma are hospitalized for an acute exacerbation. The maternal immune system is characterized by a very high T-helper-2:T-helper-1 cytokine ratio during pregnancy and thereby provides an environment essential for fetal survival but one that may aggravate asthma. Cells of the innate immune system such as monocytes and neutrophils are also increased during pregnancy, and this too can exacerbate maternal asthma. Severe or difficult-to-control asthma appears to be the major risk factor for exacerbations during pregnancy, but studies also suggest that nonadherence with controller medication and viral infections are important triggers of exacerbations during pregnancy. So far, inconsistent findings have been reported regarding the effect of fetal sex on exacerbations during pregnancy. Other risk factors for exacerbation during pregnancy include obesity, ethnicity, and reflux, whereas atopy does not appear to be a risk factor.Discussion: The incidence of asthma exacerbations during pregnancy is disturbingly high. Severe asthma – better described as difficult-to-control asthma – nonadherence with controller therapy, viral infections, obesity, and ethnicity are likely to be important risk factors for exacerbations of asthma during pregnancy, whereas inconsistent findings have been reported with regard to the importance of sex of the fetus.Keywords: acute exacerbations

  10. Comparison of Pressure Support Ventilation and Proportional Assist Ventilation Modes in Chronic Obstructive Pulmonary Disease Exacerbation

    OpenAIRE

    ŞENGÜL, Aysun; Başyiğit, İlknur; Boyacı, Haşim; Yıldız, Füsun; Ilgazlı, Ahmet

    2013-01-01

    Objective: To compare the effectiveness of pressure support ventilation and proportional assist ventilation which is two modes of non-invasive mechanical ventilation used in the treatment of chronic obstructive pulmonary disease exacerbation. Material and Methods: Total of 20 patients was included in the study. Mean age was 63±7 years. Patients were randomized as proportional assist ventilation and pressure support ventilation groups. Non-invasive mechanical ventilation was per...

  11. Acute exacerbations and pulmonary hypertension in advanced idiopathic pulmonary fibrosis.

    LENUS (Irish Health Repository)

    Judge, Eoin P

    2012-07-01

    The aim of this study was to evaluate the risk factors for and outcomes of acute exacerbations in patients with advanced idiopathic pulmonary fibrosis (IPF), and to examine the relationship between disease severity and neovascularisation in explanted IPF lung tissue. 55 IPF patients assessed for lung transplantation were divided into acute (n=27) and non-acute exacerbation (n=28) groups. Haemodynamic data was collected at baseline, at the time of acute exacerbation and at lung transplantation. Histological analysis and CD31 immunostaining to quantify microvessel density (MVD) was performed on the explanted lung tissue of 13 transplanted patients. Acute exacerbations were associated with increased mortality (p=0.0015). Pulmonary hypertension (PH) at baseline and acute exacerbations were associated with poor survival (p<0.01). PH at baseline was associated with a significant risk of acute exacerbations (HR 2.217, p=0.041). Neovascularisation (MVD) was significantly increased in areas of cellular fibrosis and significantly decreased in areas of honeycombing. There was a significant inverse correlation between mean pulmonary artery pressure and MVD in areas of honeycombing. Acute exacerbations were associated with significantly increased mortality in patients with advanced IPF. PH was associated with the subsequent development of an acute exacerbation and with poor survival. Neovascularisation was significantly decreased in areas of honeycombing, and was significantly inversely correlated with mean pulmonary arterial pressure in areas of honeycombing.

  12. Susceptibility to exacerbation in chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Hurst, John R; Vestbo, Jørgen; Anzueto, Antonio; Locantore, Nicholas; Müllerova, Hana; Tal-Singer, Ruth; Miller, Bruce; Lomas, David A; Agusti, Alvar; Macnee, William; Calverley, Peter; Rennard, Stephen; Wouters, Emiel F M; Wedzicha, Jadwiga A; NN, NN

    2010-01-01

    COPD that is independent of disease severity. METHODS: We analyzed the frequency and associations of exacerbation in 2138 patients enrolled in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study. Exacerbations were defined as events that led a care provider...

  13. Factors associated with change in exacerbation frequency in COPD

    DEFF Research Database (Denmark)

    Donaldson, Gavin C; Müllerova, Hanna; Locantore, Nicholas;

    2013-01-01

    Patients with chronic obstructive pulmonary disease (COPD) can be categorized as having frequent (FE) or infrequent (IE) exacerbations depending on whether they respectively experience two or more, or one or zero exacerbations per year. Although most patients do not change category from year to...

  14. Incidence and risk factors for exacerbations of asthma during pregnancy

    DEFF Research Database (Denmark)

    Ali, Zarqa; Ulrik, Charlotte Suppli

    2013-01-01

    Asthma is one of the most common chronic diseases among pregnant women. Acute exacerbations of asthma during pregnancy have an unfavorable impact on pregnancy outcome. This review provides an overview of current knowledge of incidence, mechanisms, and risk factors for acute exacerbations of asthma...

  15. Medically treated exacerbations in COPD by GOLD 1-4

    DEFF Research Database (Denmark)

    Ingebrigtsen, Truls S; Marott, Jacob L; Lange, Peter;

    2015-01-01

    AIM: We hypothesized that medically treated exacerbations in COPD defined as treatments with oral corticosteroids alone or in combination with antibiotics by register linkage with a nationwide prescription registry is a valid, robust and low-biased measure of exacerbations. METHODS: A total of 13......,591 individuals with COPD in the Copenhagen General Population Study (2003-2013) were linked to the Danish prescription registry. Exacerbations were defined as dispensing of oral corticosteroids alone or in combination with antibiotics, dispensed less than four weeks apart during three years of follow......-up. Construct validity of this definition of medically treated exacerbations was assessed by studying baseline determinants as well as by studying the association between GOLD 1 through 4 grades and time to first exacerbation during follow-up. RESULTS: Among individuals with COPD, 964 individuals (7.1%) had at...

  16. Mepolizumab for the reduction of exacerbations in severe eosinophilic asthma.

    Science.gov (United States)

    Russell, Richard; Brightling, Christopher

    2016-06-01

    Asthma affects over 300 million people worldwide and is severe in 10% of sufferers. Severe asthma is associated with greater morbidity and mortality particularly as a consequence of frequent exacerbations. Advances in approaches to phenotype the heterogeneity of severe asthma has established the importance of eosinophilic inflammation and emerging new therapies are broadly designed to target T2-mediated eosinophilic inflammation with the aim to reduce exacerbation frequency. Here, we summarize the evidence that eosinophilic asthma is an important pheno(endo)type and identifies a group at risk of exacerbations; that established therapies reduce exacerbations, particularly in eosinophilic severe asthma; and discuss the role of mepolizumab, an IL-5 neutralising monoclonal antibody therapy, in reducing exacerbations in severe eosinophilic asthma compared to established and other emerging therapies. PMID:27058452

  17. Acute exacerbations of chronic obstructive pulmonary disease: causes and impacts.

    Science.gov (United States)

    Chhabra, Sunil K; Dash, Devi Jyoti

    2014-01-01

    Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are recognised clinically as episodes of increased breathlessness and productive cough requiring a more intensive treatment. A subset of patients with this disease is especially prone to such exacerbations. These patients are labelled as 'frequent exacerbators'. Though yet poorly characterised in terms of host characteristics, including any genetic basis, these patients are believed to represent a distinct phenotype as they have a different natural history with a more progressive disease and a poorer prognosis than those who get exacerbations infrequently. Most exacerbations appear to be associated with infective triggers, either bacterial or viral, although 'non-infective' agents, such as air pollution and other irritants may also be important. Susceptibility to exacerbations is determined by multiple factors. Several risk factors have been identified, some of which are modifiable. Chronic obstructive pulmonary disease (COPD) exacerbations are major drivers of health status and patient-centered outcomes, and are a major reason for health care utilisation including hospitalisations and intensive care admissions. These are associated with considerable morbidity and mortality, both immediate and long-term. These episodes have a negative impact on the patient and the disease including high economic burden, increased mortality, worsening of health status, limitation of activity, and aggravation of comorbidities including cardiovascular disease, osteoporosis and neuro-psychiatric complications. Exacerbations also increase the rate of progression of disease, increasing the annual decline in lung function and leading to a poorer prognosis. Evaluation of risk of exacerbations is now included as a major component of the initial assessment of a patient with COPD in addition to the traditionally used lung function parameter, forced expiratory volume in one second (FEV1). Decreasing the risk of exacerbations

  18. Dexrazoxane exacerbates doxorubicin-induced testicular toxicity.

    Science.gov (United States)

    Levi, Mattan; Tzabari, Moran; Savion, Naphtali; Stemmer, Salomon M; Shalgi, Ruth; Ben-Aharon, Irit

    2015-10-01

    Infertility induced by anti-cancer treatments pose a major concern for cancer survivors. Doxorubicin (DXR) has been previously shown to exert toxic effects on the testicular germinal epithelium. Based upon the cardioprotective traits of dexrazoxane (DEX), we studied its potential effect in reducing DXR-induced testicular toxicity. Male mice were injected with 5  mg/kg DXR, 100  mg/kg DEX, combination of both or saline (control) and sacrificed either 1, 3 or 6 months later. Testes were excised and further processed. Glutathione and apoptosis assays were performed to determine oxidative stress. Immunohistochemistry and confocal microscopy were used to study the effects of the drugs on testicular histology and on spermatogonial reserve. DXR and the combined treatment induced a striking decline in testicular weight. DEX prevented DXR-induced oxidative stress, but enhanced DXR-induced apoptosis within the testes. Furthermore, the combined treatment depleted the spermatogonial reserve after 1 month, with impaired recovery at 3 and 6 months post-treatment. This resulted in compromised sperm parameters, testicular and epididymal weights as well as significantly reduced sperm motility, all of which were more severe than those observed in DXR-treated mice. The activity of DEX in the testis may differ from its activity in cardiomyocytes. Adding DEX to DXR exacerbates DXR-induced testicular toxicity. PMID:26329125

  19. Low dose rapamycin exacerbates autoimmune experimental uveitis.

    Directory of Open Access Journals (Sweden)

    Zili Zhang

    Full Text Available BACKGROUND: Rapamycin, a potent immune modulator, is used to treat transplant rejection and some autoimmune diseases. Uveitis is a potentially severe inflammatory eye disease, and 2 clinical trials of treating uveitis with rapamycin are under way. Unexpectedly, recent research has demonstrated that low dose rapamycin enhances the memory T cell population and function. However, it is unclear how low dose rapamycin influences the immune response in the setting of uveitis. DESIGN AND METHODS: B10.RIII mice were immunized to induce experimental autoimmune uveitis (EAU. Ocular inflammation of control and rapamycin-treated mice was compared based on histological change. ELISPOT and T cell proliferation assays were performed to assess splenocyte response to ocular antigen. In addition, we examined the effect of rapamycin on activation-induced cell death (AICD using the MitoCapture assay and Annexin V staining. RESULTS: Administration of low dose rapamycin exacerbated EAU, whereas treating mice with high dose rapamycin attenuated ocular inflammation. The progression of EAU by low dose rapamycin coincided with the increased frequency of antigen-reactive lymphocytes. Lastly, fewer rapamycin-treated T cells underwent AICD, which might contribute to exaggerated ocular inflammation and the uveitogenic immune response. CONCLUSION: These data reveal a paradoxical role for rapamycin in uveitis in a dose-dependent manner. This study has a potentially important clinical implication as rapamycin might cause unwanted consequences dependent on dosing and pharmacokinetics. Thus, more research is needed to further define the mechanism by which low dose rapamycin augments the immune response.

  20. Acute exacerbation of idiopathic pulmonary fibrosis as the initial presentation of the disease

    Directory of Open Access Journals (Sweden)

    K. Sakamoto

    2009-06-01

    Full Text Available The clinical course of patients with idiopathic pulmonary fibrosis (IPF is generally marked by a decline in pulmonary function over time, although recently there is increasing recognition that fatal deterioration from acute exacerbation can occur at any stage. The patient described in the present case study was a 65-yr-old male who presented with exertional dyspnoea and fever of 2 weeks' duration. He had no history of chronic lung disease or physiological or radiological hallmarks of pre-existing disease. He underwent surgical lung biopsy and the histological examination showed a background pattern of usual interstitial pneumonia (UIP with a pattern of focal acute diffuse alveolar damage (DAD in the area where normal lung architecture was preserved. It is notable that the pathological diagnosis of this rapidly progressive interstitial pneumonia was DAD on UIP, which is typically seen in acute exacerbations of IPF. Unusual findings on high-resolution computed tomography scan were also noted. We presume that in this case acute exacerbation developed in the very early course of IPF. Given the possibility that similar cases may have arisen among patients diagnosed with acute interstitial pneumonia or acute respiratory distress syndrome, the histopathology of rapidly progressive interstitial pneumonia may need to be revisited.

  1. Virus-induced exacerbations in asthma and COPD

    Directory of Open Access Journals (Sweden)

    Daisuke eKurai

    2013-10-01

    Full Text Available Chronic obstructive pulmonary disease (COPD is characterized by chronic airway inflammation and/or airflow limitation due to pulmonary emphysema. Chronic bronchitis, pulmonary emphysema, and bronchial asthma may all be associated with airflow limitation; therefore, exacerbation of asthma may be associated with the pathophysiology of COPD. Furthermore, recent studies have suggested that the exacerbation of asthma, namely virus-induced asthma, may be associated with a wide variety of respiratory viruses.COPD and asthma have different underlying pathophysiological processes and thus require individual therapies. Exacerbation of both COPD and asthma, which are basically defined and diagnosed by clinical symptoms, is associated with a rapid decline in lung function and increased mortality. Similar pathogens, including human rhinovirus, respiratory syncytial virus, influenza virus, parainfluenza virus and coronavirus, are also frequently detected during exacerbation of asthma and/or COPD. Immune response to respiratory viral infections, which may be related to the severity of exacerbation in each disease, varies in patients with both COPD and asthma. In this regard, it is crucial to recognize and understand both the similarities and differences of clinical features in patients with COPD and/or asthma associated with respiratory viral infections, especially in the exacerbative stage.In relation to definition, epidemiology, and pathophysiology, this review aims to summarize current knowledge concerning exacerbation of both COPD and asthma by focusing on the clinical significance of associated respiratory virus infections.

  2. Ozone Damages to Mediterranean Crops: Physiological Responses

    OpenAIRE

    Massimo Fagnano; Albino Maggio

    2011-01-01

    In this brief review we analyzed some aspects of tropospheric ozone damages to crop plants. Specifically, we addressed this issue to Mediterranean environments, where plant response to multiple stresses may either exacerbate or counteract deleterious ozone effects. After discussing the adequacy of current models to predict ozone damages to Mediterranean crops, we present a few examples of physiological responses to drought and salinity stress that generally overlap with seasonal ozone peaks i...

  3. Exacerbations of childhood asthma and ozone pollution in Atlanta

    Energy Technology Data Exchange (ETDEWEB)

    White, M.C.; Etzel, R.A.; Lloyd, C. (Centers for Disease Control and Prevention, Atlanta, GA (United States)); Wilcox, W.D. (Emory Univ. School of Medicine, Atlanta, GA (United States))

    1994-04-01

    Asthma prevalence and mortality due to asthma have been increasing during the last decade, and both the rates and the increases in rates have been higher for blacks than whites and higher for children than adults. Whether environmental factors such as air pollution contribute to these increases is unknown. The purpose of this study was to examine the relationship between emergency visits to a hospital for childhood asthma and exposure to ozone in an indigent, predominantly black population. Data were collected by abstracting clinical records for all children with asthma or reactive airway disease in one public hospital during the summer of 1990. From June 1, 1990, to August 31, 1990, 609 visits were made by children aged 1 to 16 years to an emergency clinic for treatment of asthma or reactive airway disease. Monitoring data indicated that maximum ozone levels equalled or exceeded 0.11 ppm on 6 days during the study period. The average number of visits for asthma or reactive airway disease was 37% higher on the days after those 6 days (from 6:00 PM to 6:00 PM the next day) than on other days (95% Cl, RR = 1.02-1.73). The results of the study suggest that among black children from low-income families, asthma may be exacerbated following periods of high ozone pollution. 45 refs., 1 fig., 4 tabs.

  4. Short-term blood pressure variability over 24 h and target organ damage in middle-aged men and women.

    LENUS (Irish Health Repository)

    Madden, J M

    2015-03-19

    Blood pressure variability (BPV) has been associated with cardiovascular events; however, the prognostic significance of short-term BPV remains uncertain. As uncertainty also remains as to which measure of variability most accurately describes short-term BPV, this study explores different indices and investigates their relationship with subclinical target organ damage (TOD). We used data from the Mitchelstown Study, a cross-sectional study of Irish adults aged 47-73 years (n=2047). A subsample (1207) underwent 24-h ambulatory BP monitoring (ABPM). As measures of short-term BPV, we estimated the s.d., weighted s.d. (wSD), coefficient of variation (CV) and average real variability (ARV). TOD was documented by microalbuminuria and electrocardiogram (ECG) left ventricular hypertrophy (LVH). There was no association found between any measure of BPV and LVH in both unadjusted and fully adjusted logistic regression models. Similar analysis found that ARV (24 h, day and night), s.d. (day and night) and wSD were all univariately associated with microalbuminuria and remained associated after adjustment for age, gender, smoking, body mass index (BMI), diabetes and antihypertensive treatment. However, when the models were further adjusted for the mean BP the association did not persist for all indices. Our findings illustrate choosing the appropriate summary measure, which accurately captures that short-term BPV is difficult. Despite discrepancies in values between the different measures, there was no association between any indexes of variability with TOD measures after adjustment for the mean BP.Journal of Human Hypertension advance online publication, 19 March 2015; doi:10.1038\\/jhh.2015.18.

  5. Susceptibility to exacerbation in chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Hurst, John R; Vestbo, Jørgen; Anzueto, Antonio;

    2010-01-01

    BACKGROUND: Although we know that exacerbations are key events in chronic obstructive pulmonary disease (COPD), our understanding of their frequency, determinants, and effects is incomplete. In a large observational cohort, we tested the hypothesis that there is a frequent-exacerbation phenotype of...... could be predicted on the basis of the patient's recall of previous treated events. In addition to its association with more severe disease and prior exacerbations, the phenotype was independently associated with a history of gastroesophageal reflux or heartburn, poorer quality of life, and elevated...

  6. DNA Damage Response

    OpenAIRE

    Giglia-Mari, Giuseppina; Zotter, Angelika; Vermeulen, Wim

    2011-01-01

    Structural changes to DNA severely affect its functions, such as replication and transcription, and play a major role in age-related diseases and cancer. A complicated and entangled network of DNA damage response (DDR) mechanisms, including multiple DNA repair pathways, damage tolerance processes, and cell-cycle checkpoints safeguard genomic integrity. Like transcription and replication, DDR is a chromatin-associated process that is generally tightly controlled in time and space. As DNA damag...

  7. DNA damage response

    NARCIS (Netherlands)

    G. Giglia-Mari (Giuseppina); A. Zotter (Angelika); W. Vermeulen (Wim)

    2011-01-01

    textabstractStructural changes to DNA severely affect its functions, such as replication and transcription, and play a major role in age-related diseases and cancer. A complicated and entangled network ofDNA damage response (DDR) mechanisms, including multiple DNA repair pathways, damage tolerance p

  8. Phenytoin induced Stevens-Johnson syndrome exacerbated by cefepime

    Science.gov (United States)

    Prabhu, Varsha A.; Doddapaneni, Sahiti; Thunga, Girish; Thiyagu, Rajakannan; Prabhu, M. Mukyaprana; Naha, Kushal

    2013-01-01

    Steven Johnson syndrome (SJS) is a rare drug induced mucocutaneous reaction. Here, we present an elaborate report of a 28-year-old female patient who developed Phenytoin induced SJS, which was exacerbated by cefepime. PMID:24250210

  9. Phenytoin induced Stevens-Johnson syndrome exacerbated by cefepime

    OpenAIRE

    Prabhu, Varsha A.; Sahiti Doddapaneni; Girish Thunga; Rajakannan Thiyagu; M Mukyaprana Prabhu; Kushal Naha

    2013-01-01

    Steven Johnson syndrome (SJS) is a rare drug induced mucocutaneous reaction. Here, we present an elaborate report of a 28-year-old female patient who developed Phenytoin induced SJS, which was exacerbated by cefepime.

  10. Phenytoin induced Stevens-Johnson syndrome exacerbated by cefepime

    Directory of Open Access Journals (Sweden)

    Varsha A Prabhu

    2013-01-01

    Full Text Available Steven Johnson syndrome (SJS is a rare drug induced mucocutaneous reaction. Here, we present an elaborate report of a 28-year-old female patient who developed Phenytoin induced SJS, which was exacerbated by cefepime.

  11. Fibrinogen and alpha(1)-antitrypsin in COPD exacerbations

    DEFF Research Database (Denmark)

    Sylvan Ingebrigtsen, Truls; Marott, J. L.; Rode, L.;

    2015-01-01

    Background We tested the hypotheses that fibrinogen and alpha(1)-antitrypsin are observationally and genetically associated with exacerbations in COPD. Methods We studied 13 591 individuals with COPD from the Copenhagen General Population Study (2003-2013), of whom 6857 were genotyped for FGB -455...... (rs1800790, G>A) and FGB -448 (rs4220, G>A) and had plasma fibrinogen measured. Furthermore, 13 405 individuals were genotyped for the SERPINA1 S-allele (rs17580) and the Z-allele (rs28929474) and had measurements of plasma alpha(1)-antitrypsin. Exacerbations were defined as hospital admissions or...... exacerbations in instrumental variable analyses. Results Elevated fibrinogen and alpha(1)-antitrypsin levels were associated with increased risk of exacerbations in COPD, HR=1.14 (1.07 to 1.22, p...

  12. Virus-induced exacerbations in asthma and COPD

    OpenAIRE

    DaisukeKurai

    2013-01-01

    Chronic obstructive pulmonary disease (COPD) is characterized by chronic airway inflammation and/or airflow limitation due to pulmonary emphysema. Chronic bronchitis, pulmonary emphysema, and bronchial asthma may all be associated with airflow limitation; therefore, exacerbation of asthma may be associated with the pathophysiology of COPD. Furthermore, recent studies have suggested that the exacerbation of asthma, namely virus-induced asthma, may be associated with a wide variety of respirato...

  13. Viral disruption of olfactory progenitors is exacerbated in allergic mice

    OpenAIRE

    Ueha, R.; Mukherjee, S.; Ueha, S.; de Almeida Nagata, D.E.; Sakamoto, T.; K. Kondo; Yamasoba, T.; Lukacs, N W; Kunkel, S. L.

    2014-01-01

    Upper airway viral infection in patients with airway allergy often exacerbates olfactory dysfunction, but the mechanism for this exacerbation remains unclear. Here, we examined the effects of respiratory syncytial virus (RSV) infection, in the presence or absence of airway allergy, on olfactory receptor neurons (ORNs) and their progenitors in mice. Immunohistological analyses revealed that cockroach allergen (CRA)-induced airway allergy alone did not affect the number of OMP+ mature ORNs and ...

  14. Relevance of human metapneumovirus in exacerbations of COPD

    OpenAIRE

    Bauer TT; Rausse R; Kronsbein J; Arinir U; Borg I; Rohde G; Bufe A; Schultze-Werninghaus G

    2005-01-01

    Abstract Background and methods Human metapneumovirus (hMPV) is a recently discovered respiratory virus associated with bronchiolitis, pneumonia, croup and exacerbations of asthma. Since respiratory viruses are frequently detected in patients with acute exacerbations of COPD (AE-COPD) it was our aim to investigate the frequency of hMPV detection in a prospective cohort of hospitalized patients with AE-COPD compared to patients with stable COPD and to smokers without by means of quantitative r...

  15. Exacerbations in cystic fibrosis · 1: Epidemiology and pathogenesis

    OpenAIRE

    Goss, Christopher H.; Burns, Jane L.

    2007-01-01

    With the improving survival of patients with cystic fibrosis (CF), the clinical spectrum of this complex multisystem disease continues to evolve. One of the most important clinical events for patients with CF in the course of this disease is an acute pulmonary exacerbation. Clinical and microbial epidemiology studies of CF pulmonary exacerbations continue to provide important insight into the course, prognosis and complications of the disease. This review provides a summary of the pathophysio...

  16. Bacterial etiology in acute hospitalized chronic obstructive pulmonary disease exacerbations

    OpenAIRE

    Asli Gorek Dilektasli; Ezgi Demirdogen Cetinoglu; Nilufer Aylin Acet Ozturk; Funda Coskun; Guven Ozkaya; Ahmet Ursavas; Cuneyt Ozakin; Mehmet Karadag; Esra Uzaslan

    2016-01-01

    Introduction. The most common cause of acute COPD exacerbation (AECOPD) is the respiratory tract infections. We sought to determine the bacteriological etiology of hospitalized acute exacerbations of COPD requiring hospitalization in consecutive two years. Methods. We aimed to determine the bacteriological etiology underlying in patients whom admitted to Uludag University Faculty of Medicine, Department of Pulmonary Medicine and hospitalized with AECOPD in the last two years. Medical records ...

  17. Incidence and risk factors for exacerbations of asthma during pregnancy

    OpenAIRE

    Ali Z; Ulrik CS

    2013-01-01

    Zarqa Ali, Charlotte Suppli UlrikDepartment of Pulmonary Medicine, Hvidovre Hospital and University of Copenhagen, Copenhagen, DenmarkBackground: Asthma is one of the most common chronic diseases among pregnant women. Acute exacerbations of asthma during pregnancy have an unfavorable impact on pregnancy outcome. This review provides an overview of current knowledge of incidence, mechanisms, and risk factors for acute exacerbations of asthma during pregnancy.Methods: A narrative literature rev...

  18. Self-reported sleep quality and acute exacerbations of chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Geiger-Brown J

    2015-02-01

    Full Text Available Jeanne Geiger-Brown,1 Sarah Lindberg,2 Samuel Krachman,3 Charlene E McEvoy,4 Gerard J Criner,3 John E Connett,2 Richard K Albert,5 Steven M Scharf6 1Center for Health Outcomes Research, University of Maryland School of Nursing, Baltimore, MD, 2University of Minnesota School of Public Health, Division of Biostatistics, Minneapolis, MN, 3Pulmonary and Critical Care Medicine, Department of Medicine, Temple University School of Medicine, Philadelphia, PA, 4Health Partners Institute of Education and Research, St Paul, MN, 5The Medicine Service, Denver Health and Department of Medicine, the University of Colorado Denver Health Sciences Center, Denver, CO, 6Department of Medicine, Pulmonary and Critical Care Division, University of Maryland School of Medicine, Baltimore, MD, USA Background: Many patients with chronic obstructive pulmonary disease (COPD suffer from poor sleep quality. We hypothesized that poor sleep quality in otherwise stable patients predicted exacerbations in these patients. Methods: This is a secondary analysis of the results of a previously published randomized trial of azithromycin in 1,117 patients with moderate to severe COPD who were clinically stable on enrollment. Sleep quality was measured using the Pittsburgh Sleep Quality Index. Other quality of life indices included the Medical Outcome Study 36-item Short Form Health Survey and the St Georges Respiratory Questionnaire. Outcomes included time to first exacerbation and exacerbation rate. Results: Sleep quality was “poor” (Pittsburgh Sleep Quality Index >5 in 53% of participants but was not related to age or severity of airflow obstruction. Quality of life scores were worse in “poor” sleepers than in “good” sleepers. Major classes of comorbid conditions, including psychiatric, neurologic, and musculoskeletal disease, were more prevalent in the “poor” sleepers. Unadjusted time to first exacerbation was shorter (190 versus 239 days and exacerbation rate (1

  19. Severe and Moderate Asthma Exacerbations in Asthmatic Children and Exposure to Ambient Air Pollutants

    Science.gov (United States)

    Tétreault, Louis-Francois; Doucet, Marieve; Gamache, Philippe; Fournier, Michel; Brand, Allan; Kosatsky, Tom; Smargiassi, Audrey

    2016-01-01

    Background: It is well established that short-term exposure to ambient air pollutants can exacerbate asthma, the role of early life or long-term exposure is less clear. We assessed the association between severe asthma exacerbations with both birth and annual exposure to outdoor air pollutants with a population-based cohort of asthmatic children in the province of Quebec (Canada). Method: Exacerbations of asthma occurring between 1 April 1996 and 31 March 2011 were defined as one hospitalization or emergency room visit with a diagnosis of asthma for children (<13 years old) already diagnosed with asthma. Annual daily average concentrations of ozone (O3) and nitrogen dioxide (NO2) were estimated at the child’s residential postal code. Satellite based levels of fine particulate (PM2.5) estimated for a grid of 10 km by 10 km were also assigned to postal codes of residence for the whole province. Hazard ratios (HRs) were estimated from Cox models with a gap time approach for both birth and time-dependant exposure. Results: Of the 162,752 asthmatic children followed (1,020,280 person-years), 35,229 had at least one asthma exacerbation. The HRs stratified by age groups and adjusted for the year of birth, the ordinal number of exacerbations, sex, as well as material and social deprivation, showed an interquartile range increase in the time-dependant exposure to NO2 (4.95 ppb), O3 (3.85 ppb), and PM2.5 (1.82 μg/m3) of 1.095 (95% CI 1.058–1.131), 1.052 (95% CI 1.037–1.066) and 1.025 (95% CI 1.017–1.031), respectively. While a positive association was found to PM2.5, no associations were found between exposure at birth to NO2 or O3. Conclusions: Our results support the conclusion, within the limitation of this study, that asthma exacerbations in asthmatic children are mainly associated with time dependent residential exposures less with exposure at birth. PMID:27490556

  20. Markers of exacerbation severity in chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Walker Michael J

    2006-05-01

    Full Text Available Abstract Background Patients with chronic obstructive pulmonary disease (COPD can experience 'exacerbations' of their conditions. An exacerbation is an event defined in terms of subjective descriptors or symptoms, namely dyspnoea, cough and sputum that worsen sufficiently to warrant a change in medical management. There is a need for reliable markers that reflect the pathological mechanisms that underlie exacerbation severity and that can be used as a surrogate to assess treatment effects in clinical studies. Little is known as to how existing study variables and suggested markers change in both the stable and exacerbation phases of COPD. In an attempt to find the best surrogates for exacerbations, we have reviewed the literature to identify which of these markers change in a consistent manner with the severity of the exacerbation event. Methods We have searched standard databases between 1966 to July 2004 using major keywords and terms. Studies that provided demographics, spirometry, potential markers, and clear eligibility criteria were included in this study. Central tendencies and dispersions for all the variables and markers reported and collected by us were first tabulated according to sample size and ATS/ERS 2004 Exacerbation Severity Levels I to III criteria. Due to the possible similarity of patients in Levels II and III, the data was also redefined into categories of exacerbations, namely out-patient (Level I and in-patient (Levels II & III combined. For both approaches, we performed a fixed effect meta-analysis on each of the reported variables. Results We included a total of 268 studies reported between 1979 to July 2004. These studies investigated 142,407 patients with COPD. Arterial carbon dioxide tension and breathing rate were statistically different between all levels of exacerbation severity and between in out- and in-patient settings. Most other measures showed weak relationships with either level or setting, or they had

  1. Risk of death and readmission of hospital-admitted COPD exacerbations: European COPD Audit.

    Science.gov (United States)

    Hartl, Sylvia; Lopez-Campos, Jose Luis; Pozo-Rodriguez, Francisco; Castro-Acosta, Ady; Studnicka, Michael; Kaiser, Bernhard; Roberts, C Michael

    2016-01-01

    Studies report high in-hospital and post-discharge mortality of chronic obstructive pulmonary disease (COPD) exacerbations varying depending upon patient characteristics, hospital resources and treatment standards. This study aimed to investigate the patient, resource and organisational factors associated with in-hospital and 90-day post-discharge mortality and readmission of COPD exacerbations within the European COPD Audit. The audit collected data of COPD exacerbation admissions from 13 European countries.On admission, only 49.7% of COPD patients had spirometry results available and only 81.6% had blood gases taken. Using logistic regression analysis, the risk associated with in-hospital and post-discharge mortality was higher age, presence of acidotic respiratory failure, subsequent need for ventilatory support and presence of comorbidity. In addition, the 90-day risk of COPD readmission was associated with previous admissions. Only the number of respiratory specialists per 1000 beds, a variable related to hospital resources, decreased the risk of post-discharge mortality.The European COPD Audit identifies risk factors associated with in-hospital and post-discharge mortality and COPD readmission. Addressing the deficiencies in acute COPD care such as making spirometry available and measuring blood gases and providing noninvasive ventilation more regularly would provide opportunities to improve COPD outcomes. PMID:26493806

  2. Mitochondrial iron accumulation exacerbates hepatic toxicity caused by hepatitis C virus core protein

    Energy Technology Data Exchange (ETDEWEB)

    Sekine, Shuichi; Ito, Konomi; Watanabe, Haruna; Nakano, Takafumi [Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675 (Japan); Moriya, Kyoji; Shintani, Yoshizumi; Fujie, Hajime; Tsutsumi, Takeya; Miyoshi, Hideyuki; Fujinaga, Hidetake; Shinzawa, Seiko; Koike, Kazuhiko [Department of Internal Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655 (Japan); Horie, Toshiharu, E-mail: t.horie@thu.ac.jp [Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675 (Japan)

    2015-02-01

    Patients with long-lasting hepatitis C virus (HCV) infection are at major risk of hepatocellular carcinoma (HCC). Iron accumulation in the livers of these patients is thought to exacerbate conditions of oxidative stress. Transgenic mice that express the HCV core protein develop HCC after the steatosis stage and produce an excess of hepatic reactive oxygen species (ROS). The overproduction of ROS in the liver is the net result of HCV core protein-induced dysfunction of the mitochondrial respiratory chain. This study examined the impact of ferric nitrilacetic acid (Fe-NTA)-mediated iron overload on mitochondrial damage and ROS production in HCV core protein-expressing HepG2 (human HCC) cells (Hep39b cells). A decrease in mitochondrial membrane potential and ROS production were observed following Fe-NTA treatment. After continuous exposure to Fe-NTA for six days, cell toxicity was observed in Hep39b cells, but not in mock (vector-transfected) HepG2 cells. Moreover, mitochondrial iron ({sup 59}Fe) uptake was increased in the livers of HCV core protein-expressing transgenic mice. This increase in mitochondrial iron uptake was inhibited by Ru360, a mitochondrial Ca{sup 2+} uniporter inhibitor. Furthermore, the Fe-NTA-induced augmentation of mitochondrial dysfunction, ROS production, and cell toxicity were also inhibited by Ru360 in Hep39b cells. Taken together, these results indicate that Ca{sup 2+} uniporter-mediated mitochondrial accumulation of iron exacerbates hepatocyte toxicity caused by the HCV core protein. - Highlights: • Iron accumulation in the livers of patients with hepatitis C virus (HCV) infection is thought to exacerbate oxidative stress. • The impact of iron overload on mitochondrial damage and ROS production in HCV core protein-expressing cells were examined. • Mitochondrial iron uptake was increased in the livers of HCV core protein-expressing transgenic mice. • Ca{sup 2+} uniporter-mediated mitochondrial accumulation of iron exacerbates

  3. Mfn2 deficiency links age-related sarcopenia and impaired autophagy to activation of an adaptive mitophagy pathway.

    Science.gov (United States)

    Sebastián, David; Sorianello, Eleonora; Segalés, Jessica; Irazoki, Andrea; Ruiz-Bonilla, Vanessa; Sala, David; Planet, Evarist; Berenguer-Llergo, Antoni; Muñoz, Juan Pablo; Sánchez-Feutrie, Manuela; Plana, Natàlia; Hernández-Álvarez, María Isabel; Serrano, Antonio L; Palacín, Manuel; Zorzano, Antonio

    2016-08-01

    Mitochondrial dysfunction and accumulation of damaged mitochondria are considered major contributors to aging. However, the molecular mechanisms responsible for these mitochondrial alterations remain unknown. Here, we demonstrate that mitofusin 2 (Mfn2) plays a key role in the control of muscle mitochondrial damage. We show that aging is characterized by a progressive reduction in Mfn2 in mouse skeletal muscle and that skeletal muscle Mfn2 ablation in mice generates a gene signature linked to aging. Furthermore, analysis of muscle Mfn2-deficient mice revealed that aging-induced Mfn2 decrease underlies the age-related alterations in metabolic homeostasis and sarcopenia. Mfn2 deficiency reduced autophagy and impaired mitochondrial quality, which contributed to an exacerbated age-related mitochondrial dysfunction. Interestingly, aging-induced Mfn2 deficiency triggers a ROS-dependent adaptive signaling pathway through induction of HIF1α transcription factor and BNIP3. This pathway compensates for the loss of mitochondrial autophagy and minimizes mitochondrial damage. Our findings reveal that Mfn2 repression in muscle during aging is a determinant for the inhibition of mitophagy and accumulation of damaged mitochondria and triggers the induction of a mitochondrial quality control pathway. PMID:27334614

  4. UV Photography Shows Hidden Sun Damage

    Science.gov (United States)

    ... care Younger skin Causes of aging skin Creating anti-aging plan Fillers giving patients better, longer-lasting results Maximizing anti-aging products Selecting anti-aging products Sun damage Wrinkle ...

  5. Glucose tolerance during pulmonary exacerbations in children with cystic fibrosis.

    Directory of Open Access Journals (Sweden)

    John Widger

    Full Text Available BACKGROUND: Patients with Cystic Fibrosis (CF are relatively insulinopenic and are at risk of diabetes, especially during times of stress. There is a paucity of data in the literature describing glucose tolerance during CF pulmonary exacerbations. We hypothesised that glucose tolerance would be worse during pulmonary exacerbations in children with CF than during clinical stability. METHODS: Patients with CF, 10 years or older, admitted with a pulmonary exacerbation underwent an OGTT within 48 hours of admission. A repeat OGTT was performed 4 to 6 weeks post discharge when the patients were well. RESULTS: Nine patients completed the study. Four patients were found to have normal glucose tolerance, 3 with impaired and 2 with CF related diabetes during the exacerbation. Mean change in 2-hour glucose was 1.1 mmol (SD = 0.77. At the follow up OGTT, 8 of 9 (89% remained within their respective glucose tolerance status groupings. CONCLUSION: The findings of this study show that there is little difference in glucose tolerance during CF exacerbations compared to clinical stability in the majority of patients.

  6. Asthma exacerbations during pregnancy: incidence and association with adverse pregnancy outcomes

    OpenAIRE

    Murphy, V E; Clifton, V.L.; Gibson, P G

    2006-01-01

    Exacerbations of asthma during pregnancy represent a significant clinical problem and may be related to poor pregnancy outcomes. A systematic review of the literature was conducted for publications related to exacerbations during pregnancy. Four studies with a control group (no asthma) and two groups of women with asthma (exacerbation, no exacerbation) were included in meta‐analyses using fixed effects models. During pregnancy, exacerbations of asthma which require medical intervention occur ...

  7. Accelerated extracellular matrix turnover during exacerbations of COPD

    DEFF Research Database (Denmark)

    Sand, Jannie M B; Knox, Alan J; Lange, Peter;

    2015-01-01

    BACKGROUND: Exacerbations of chronic obstructive pulmonary disease (COPD) contribute significantly to disease progression. However, the effect on tissue structure and turnover is not well described. There is an urgent clinical need for biomarkers of disease activity associated with disease...... progression. Extracellular matrix (ECM) turnover reflects activity in tissues and consequently assessment of ECM turnover may serve as biomarkers of disease activity. We hypothesized that the turnover of lung ECM proteins were altered during exacerbations of COPD. METHODS: 69 patients with COPD hospitalised...... elevated levels of circulating fragments of structural proteins, which may serve as markers of disease activity. This suggests that patients with COPD have accelerated ECM turnover during exacerbations which may be related to disease progression....

  8. Paradoxical exacerbation of chronic plaque psoriasis by sorafenib.

    Science.gov (United States)

    Yiu, Z Z N; Ali, F R; Griffiths, C E M

    2016-06-01

    Vascular endothelial growth factor (VEGF) antagonists have been investigated as a potential treatment for psoriasis, but there have been reports of VEGF antagonists triggering and/or exacerbating pre-existing psoriasis. We present the case of a 61-year old-man with exacerbation of pre-existing psoriasis after treatment with sorafenib, a small molecule inhibitor of the tyrosine kinase domain of the VEGF receptor, and we review the literature for other published cases of sorafenib-induced or sorafenib-exacerbated psoriasis. Clinicians, including both dermatologists and oncologists, should be aware of this potential side-effect of sorafenib in addition to the other cutaneous side effects reported for this drug. PMID:26667599

  9. COPD exacerbations in general practice: variability in oral prednisolone courses

    Directory of Open Access Journals (Sweden)

    de Vries Marianne

    2012-01-01

    Full Text Available Abstract Background The use of oral corticosteroids as treatment of COPD exacerbations in primary care is well established and evidence-based. However, the most appropriate dosage regimen has not been determined and remains controversial. Corticosteroid therapy is associated with a number of undesirable side effects, including hyperglycaemias, so differences in prescribing might be relevant. This study examines the differences between GPs in dosage and duration of prednisolone treatment in patients with a COPD exacerbation. It also investigates the number of general practitioners (GPs who adjust their treatment according to the presence of diabetic co-morbidity. Methods Cross-sectional study among 219 GPs and 25 GPs in training, located in the Northern part of the Netherlands. Results The response rate was 69%. Nearly every GP prescribed a continuous dose of prednisolone 30 mg per day. Among GPs there were substantial differences in treatment duration. GPs prescribed courses of five, seven, ten, or fourteen days. A course of seven days was most common. The duration of treatment depended on exacerbation and disease severity. A course of five days was especially prescribed in case of a less severe exacerbation. In a more severe exacerbation duration of seven to fourteen days was more common. Hardly any GP adjusted treatment to the presence of diabetic co-morbidity. Conclusion Under normal conditions GPs prescribe prednisolone quite uniformly, within the range of the current Dutch guidelines. There is insufficient guidance regarding how to adjust corticosteroid treatment to exacerbation severity, disease severity and the presence of diabetic co-morbidity. Under these circumstances, there is a substantial variation in treatment duration.

  10. Ataxia telangiectasia-mutated kinase deficiency exacerbates left ventricular dysfunction and remodeling late after myocardial infarction.

    Science.gov (United States)

    Daniel, Laura L; Scofield, Stephanie L C; Thrasher, Patsy; Dalal, Suman; Daniels, Christopher R; Foster, Cerrone R; Singh, Mahipal; Singh, Krishna

    2016-08-01

    Ataxia telangiectasia-mutated kinase (ATM), a cell cycle checkpoint protein, is activated in response to DNA damage and oxidative stress. We have previously shown that ATM deficiency is associated with increased apoptosis and fibrosis and attenuation of cardiac dysfunction early (1-7 days) following myocardial infarction (MI). Here, we tested the hypothesis that enhanced fibrosis and apoptosis, as observed early post-MI during ATM deficiency, exacerbate cardiac dysfunction and remodeling in ATM-deficient mice late post-MI. MIs were induced in wild-type (WT) and ATM heterozygous knockout (hKO) mice by ligation of the left anterior descending artery. Left ventricular (LV) structural and functional parameters were assessed by echocardiography 14 and 28 days post-MI, whereas biochemical parameters were measured 28 days post-MI. hKO-MI mice exhibited exacerbated LV dysfunction as observed by increased LV end-systolic volume and decreased percent fractional shortening and ejection fraction. Infarct size and thickness were not different between the two genotypes. Myocyte cross-sectional area was greater in hKO-MI group. The hKO-MI group exhibited increased fibrosis in the noninfarct and higher expression of α-smooth muscle actin (myofibroblast marker) in the infarct region. Apoptosis and activation of GSK-3β (proapoptotic kinase) were significantly lower in the infarct region of hKO-MI group. Matrix metalloproteinase 2 (MMP-2) expression was not different between the two genotypes. However, MMP-9 expression was significantly lower in the noninfarct region of hKO-MI group. Thus ATM deficiency exacerbates cardiac remodeling late post-MI with effects on cardiac function, fibrosis, apoptosis, and myocyte hypertrophy. PMID:27288435

  11. Interleukin-1 exacerbates focal cerebral ischemia and reduces ischemic brain temperature in the rat.

    Science.gov (United States)

    Parry-Jones, Adrian R; Liimatainen, Timo; Kauppinen, Risto A; Gröhn, Olli H J; Rothwell, Nancy J

    2008-06-01

    The proinflammatory cytokine interleukin-1 (IL-1) is a key mediator of inflammation in cerebral ischemia, but its precise mechanisms of action remain elusive. Temperature is critical to outcome in brain injury and given the importance of IL-1 in pyrogenesis this has clear mechanistic implications. IL-1 exacerbates ischemia independently of core (rectal) temperature. However, it is temperature in the ischemic brain that influences outcome and rectal temperature is likely to be a poor surrogate marker. This study tested the hypothesis that IL-1 exacerbates cerebral ischemia by increasing ischemic brain temperature. Wistar rats undergoing transient middle cerebral artery occlusion received either 4 microg/kg IL-1 (n=9) or vehicle (n=10) intraperitoneally. NMR-generated maps of brain temperature, tissue perfusion, and the trace of the diffusion tensor were collected during occlusion, early reperfusion, and at 24 hr. IL-1 significantly increased ischemic damage at 24 hr by 35% but rectal temperature did not vary significantly between groups. However, ischemic brain was 1.7 degrees C cooler on reperfusion in IL-1-treated animals (vs. vehicle) and a corresponding reduction in cerebral blood flow was identified in the ischemic striatum. Contrary to the stated hypothesis, IL-1 reduced ischemic brain temperature during reperfusion and this may be due to a reduction in tissue perfusion. PMID:18421691

  12. High-dose N-acetylcysteine in the prevention of COPD exacerbations: rationale and design of the PANTHEON Study.

    Science.gov (United States)

    Zheng, Jin-Ping; Wen, Fu-Qiang; Bai, Chun-Xue; Wan, Huan-Ying; Kang, Jian; Chen, Ping; Yao, Wan-Zhen; Ma, Li-Jun; Xia, Qi-Kui; Gao, Yi; Zhong, Nan-Shan

    2013-04-01

    Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation; from a pathophysiological point of view it involves many components, including mucus hypersecretion, oxidative stress and inflammation. N-acetylcysteine (NAC) is a mucolytic agent with antioxidant and anti-inflammatory properties. Long-term efficacy of NAC 600mg/d in COPD is controversial; a dose-effect relationship has been demonstrated, but at present it is not known whether a higher dose provides clinical benefits. The PANTHEON Study is a prospective, ICS stratified, randomized, double-blind, placebo-controlled, parallel-group, multi-center trial designed to assess the efficacy and safety of high-dose (1200 mg/daily) NAC treatment for one year in moderate-to-severe COPD patients. The primary endpoint is the annual exacerbation rate. Secondary endpoints include recurrent exacerbations hazard ratio, time to first exacerbation, as well as quality of life and pulmonary function. The hypothesis, design and methodology are described and baseline characteristics of recruited patients are presented. 1006 COPD patients (444 treated with maintenance ICS, 562 ICS naive, aged 66.27±8.76 yrs, average post-bronchodilator FEV1 48.95±11.80 of predicted) have been randomized at 34 hospitals in China. Final results of this study will provide objective data on the effects of high-dose (1200 mg/daily) long-term NAC treatment in the prevention of COPD exacerbations and other outcome variables. PMID:23061828

  13. Efficacy of amoxycillin versus amoxycillin/clavulanate in acute exacerbations of chronic pulmonary obstructive disease in primary care

    Science.gov (United States)

    Llor, Carl; Hernández, Silvia; Ribas, Anna; Álvarez, Carmen; Cots, Josep Maria; Bayona, Carolina; González, Isabel; Miravitlles, Marc

    2009-01-01

    Background Amoxycillin/clavulanate is considered first-line treatment for ambulatory exacerbations of COPD. However, narrow-spectrum antibiotics may be as useful for mild to moderate patients. Objective To compare the clinical efficacy of amoxycillin versus amoxicyllin/clavulanate in exacerbations of COPD in primary care. Methods A randomized, double-blind, noninferiority clinical trial was carried out in eight primary care centers in Catalonia, Spain. Spirometrically-diagnosed patients older than 40 years with COPD, without criteria of hospitalization and Anthonisen’s types I or II exacerbations were included. The main outcome was clinical cure at the end of treatment (EOT) visit on day 10. Results A total of 137 patients were enrolled in the study (68 assigned to amoxycillin and 69 to amoxycillin/clavulanate). The mean forced expiratory flow in one second was 61.6% and the mean age was 71.4 years. At EOT, 92.8% of patients in the amoxycillin/clavulanate and 90.9% in the amoxycillin group were considered clinically cured, a statistically non-significant difference. Adverse effects were observed in 11 subjects, 3 in the amoxycillin group and 8 in the amoxycillin/clavulanate group, 2 of whom required a change in treatment. Conclusions Amoxycillin was at least as effective clinically and as safe as amoxycilin/ clavulanate in the treatment of acute exacerbations of COPD in mild to moderate patients in primary care. PMID:19436696

  14. Oxygen therapy in acute exacerbations of chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Brill SE

    2014-11-01

    Full Text Available Simon E Brill, Jadwiga A Wedzicha Airway Disease Section, National Heart and Lung Institute, Imperial College, London, UK Abstract: Acute exacerbations of chronic obstructive pulmonary disease (COPD are important events in the history of this debilitating lung condition. Associated health care utilization and morbidity are high, and many patients require supplemental oxygen or ventilatory support. The last 2 decades have seen a substantial increase in our understanding of the best way to manage the respiratory failure suffered by many patients during this high-risk period. This review article examines the evidence underlying supplemental oxygen therapy during exacerbations of COPD. We first discuss the epidemiology and pathophysiology of respiratory failure in COPD during exacerbations. The rationale and evidence underlying oxygen therapy, including the risks when administered inappropriately, are then discussed, along with further strategies for ventilatory support. We also review current recommendations for best practice, including methods for improving oxygen provision in the future. Keywords: chronic obstructive pulmonary disease (COPD, exacerbation, oxygen therapy, respiratory failure, hypercapnia

  15. Withdrawal of inhaled glucocorticoids and exacerbations of COPD

    DEFF Research Database (Denmark)

    Magnussen, Helgo; Disse, Bernd; Rodriguez-Roisin, Roberto;

    2014-01-01

    BACKGROUND: Treatment with inhaled glucocorticoids in combination with long-acting bronchodilators is recommended in patients with frequent exacerbations of severe chronic obstructive pulmonary disease (COPD). However, the benefit of inhaled glucocorticoids in addition to two long-acting bronchod......BACKGROUND: Treatment with inhaled glucocorticoids in combination with long-acting bronchodilators is recommended in patients with frequent exacerbations of severe chronic obstructive pulmonary disease (COPD). However, the benefit of inhaled glucocorticoids in addition to two long......-acting bronchodilators has not been fully explored. METHODS: In this 12-month, double-blind, parallel-group study, 2485 patients with a history of exacerbation of COPD received triple therapy consisting of tiotropium (at a dose of 18 μg once daily), salmeterol (50 μg twice daily), and the inhaled glucocorticoid...... fluticasone propionate (500 μg twice daily) during a 6-week run-in period. Patients were then randomly assigned to continued triple therapy or withdrawal of fluticasone in three steps over a 12-week period. The primary end point was the time to the first moderate or severe COPD exacerbation. Spirometric...

  16. Novel Human Rhinoviruses and Exacerbation of Asthma in Children 1

    OpenAIRE

    Khetsuriani, Nino; Lu, Xiaoyan; Teague, W. Gerald; Kazerouni, Neely; Anderson, Larry J.; Erdman, Dean D.

    2008-01-01

    To determine links between human rhinoviruses (HRV) and asthma, we used data from a case–control study, March 2003–February 2004, among children with asthma. Molecular characterization identified several likely new HRVs and showed that association with asthma exacerbations was largely driven by HRV-A and a phylogenetically distinct clade of 8 strains, genogroup C.

  17. Novel Human Rhinoviruses and Exacerbation of Asthma in Children1

    Science.gov (United States)

    Khetsuriani, Nino; Lu, Xiaoyan; Teague, W. Gerald; Kazerouni, Neely; Anderson, Larry J.

    2008-01-01

    To determine links between human rhinoviruses (HRV) and asthma, we used data from a case–control study, March 2003–February 2004, among children with asthma. Molecular characterization identified several likely new HRVs and showed that association with asthma exacerbations was largely driven by HRV-A and a phylogenetically distinct clade of 8 strains, genogroup C. PMID:18976575

  18. How Clinical Diagnosis Might Exacerbate the Stigma of Mental Illness

    Science.gov (United States)

    Corrigan, Patrick W.

    2007-01-01

    Stigma can greatly exacerbate the experience of mental illness. Diagnostic classification frequently used by clinical social workers may intensify this stigma by enhancing the public's sense of "groupness" and "differentness" when perceiving people with mental illness. The homogeneity assumed by stereotypes may lead mental health professionals and…

  19. Thiazolidinediones are associated with a reduced risk of COPD exacerbations

    Directory of Open Access Journals (Sweden)

    Rinne ST

    2015-08-01

    Full Text Available Seppo T Rinne,1,2 Chuan-Fen Liu,3,4 Laura C Feemster,3,5 Bridget F Collins,3,5 Christopher L Bryson,3,6 Thomas G O’Riordan,7 David H Au3,4 1Department of Veterans Affairs, VA Connecticut Healthcare System, West Haven, 2Division of Pulmonary and Critical Care, Yale University, New Haven, CT, USA; 3VA Puget Sound Health Care System, Department of Veterans Affairs, 4Department of Health Services, University of Washington, 5Division of Pulmonary and Critical Care, University of Washington, 6Division of General Internal Medicine, University of Washington, 7Gilead Sciences, Inc., Seattle, WA, USA Background: Thiazolidinediones (TZDs are oral antihyperglycemic medications that are selective agonists to peroxisome proliferator-activated receptor gamma and have been shown to have potent anti-inflammatory effects in the lung.Objective: The purpose of this study was to assess whether exposure to TZDs is associated with a decreased risk of chronic obstructive pulmonary disease (COPD exacerbation.Methods: A cohort study was performed by collecting data on all US veterans with diabetes and COPD who were prescribed oral antihyperglycemic medications during from period of October 1, 2005 to September 30, 2007. Patients who had two or more prescriptions for TZDs were compared with patients who had two or more prescriptions for an alternative oral antihyperglycemic medication. Multivariable negative binomial regression was performed with adjustment for potential confounding factors. The primary outcome was COPD exacerbations, including both inpatient and outpatient exacerbations.Results: We identified 7,887 veterans who were exposed to TZD and 42,347 veterans who were exposed to non-TZD oral diabetes medications. COPD exacerbations occurred in 1,258 (16% of the TZD group and 7,789 (18% of the non-TZD group. In multivariable negative binomial regression, there was a significant reduction in the expected number of COPD exacerbations among patients who were

  20. Lipocalin 2 deficiency dysregulates iron homeostasis and exacerbates endotoxin-induced sepsis

    DEFF Research Database (Denmark)

    Srinivasan, Gayathri; Aitken, Jesse D; Zhang, Benyue;

    2012-01-01

    elevated intracellular labile iron. In this study, we report that LPS induced systemic Lcn2 by 150-fold in wild-type mice at 24 h. Relative to wild-type littermates, Lcn2KO mice were markedly more sensitive to endotoxemia, exhibiting elevated indices of organ damage (transaminasemia, lactate dehydrogenase......) and increased mortality. Such exacerbated endotoxemia was associated with substantially increased caspase-3 cleavage and concomitantly elevated immune cell apoptosis. Furthermore, cells from Lcn2KO mice were hyperresponsive to LPS ex vivo, exhibiting elevated cytokine secretion. Additionally, Lcn2KO...... mice exhibited delayed LPS-induced hypoferremia despite normal hepatic hepcidin expression and displayed decreased levels of the tissue redox state indicators cysteine and glutathione in liver and plasma. Desferroxamine, an iron chelator, significantly protects Lcn2KO mice from LPS-induced toxicity...

  1. Impacts of coexisting bronchial asthma on severe exacerbations in mild-to-moderate COPD: results from a national database

    Directory of Open Access Journals (Sweden)

    Lee H

    2016-04-01

    prevalence of severe exacerbations and impact of asthma on severe exacerbations, especially in patients with mild-to-moderate COPD.Methods: Patients with mild-to-moderate COPD (≥40 years were extracted from Korean National Health and Nutrition Examination Survey data (2007–2012 and were linked to the national health insurance reimbursement database to obtain medical service utilization records.Results: Of the 2,397 patients with mild-to-moderate COPD, 111 (4.6% had severe exacerbations over the 6 years (0.012/person-year. Severe exacerbations were more frequent in the COPD patients with concomitant self-reported physician-diagnosed asthma compared with only COPD patients (P<0.001. A multiple logistic regression presented that asthma was an independent risk factor of severe exacerbations in patients with mild-to-moderate COPD regardless of adjustment for all possible confounding factors (adjusted odds ratio, 1.67; 95% confidence interval, 1.002–2.77, P=0.049. In addition, age, female, poor lung function, use of inhalers, and low EuroQoL five dimensions questionnaire index values were independently associated with severe exacerbation in patients with mild-to-moderate COPD.Conclusion: In this population-based study, the prevalence of severe exacerbations in patients with mild-to-moderate COPD was relatively low, compared with previous clinical interventional studies. Coexisting asthma significantly impacted the frequency of severe exacerbations in patients with mild-to-moderate COPD, suggesting application of an exacerbation preventive strategy in these patients. Keywords: bronchial asthma, chronic obstructive pulmonary disease, acute exacerbation

  2. Hourly differences in air pollution on the risk of asthma exacerbation

    International Nuclear Information System (INIS)

    We investigated the association between hourly differences in air pollution and asthma exacerbation in Korea using asthma-related emergency department data and verified seasonality and demographic modifiers with an hourly temporal resolution. We applied time-stratified case-crossover adjusted for weather and influenza; the lag was stratified as 1–6, 7–12, 13–18, 19–24, 25–48, and49–72 h. Odds ratios (95% confidence interval) per interquartile range increase were 1.05 (1.00–1.11) after 1–6 h for PM10–2.5 and 1.10 (1.04–1.16) after 19–24 h for O3. Effect size was 1.14 (1.06–1.22) at a 1–6 h lag in spring for PM10–2.5, and 1.25 (1.03–1.51) at a 25–48 h lag in winter for O3. O3 effects were age- and low socio-economic status-modified at a 7–12 h lag [1.25 (1.04–1.51)]. Increased PM10–2.5 and O3 increased the risk of asthma exacerbation; the effect of PM10–2.5 was most immediate. - Highlights: • We examined hourly differences in air pollution levels and asthma exacerbation risk. • Increased PM10–2.5 and O3 levels increased the risk of asthma exacerbation. • The effect of PM10–2.5 was more immediate than other pollutants. • The effect of O3 was modified by age and socio-economic status. • O3 has a longer lag effect, particularly in winter. - Hourly increments of PM10–2.5 and O3 induced an increased risk of asthma-related emergency room visits, and the effect of PM10–2.5 was most immediate

  3. Skin aging:

    OpenAIRE

    Puizina-Ivić, Neira

    2008-01-01

    There are two main processes that induce skin aging: intrinsic and extrinsic. A stochastic process that implies random cell damage as a result of mutations during metabolic processes due to the production of free radicals is also implicated. Extrinsic aging is caused by environmental factors such as sun exposure, air pollution, smoking, alcohol abuse, and poor nutrition. Intrinsicaging reflects the genetic background and depends on time. Various expressions of intrinsic aging include smooth, ...

  4. The clinical and economic impact of exacerbations of chronic obstructive pulmonary disease: a cohort of hospitalized patients.

    Directory of Open Access Journals (Sweden)

    Francesco Blasi

    Full Text Available Chronic Obstructive Pulmonary Disease (COPD is a common disease with significant health and economic consequences. This study assesses the burden of COPD in the general population, and the influence of exacerbations (E-COPD on disease progression and costs.This is a secondary data analysis of healthcare administrative databases of the region of Lombardy, in northern Italy. The study included ≥ 40 year-old patients hospitalized for a severe E-COPD (index event during 2006. Patients were classified in relation to the number and type of E-COPD experienced in a three-year pre-index period. Subjects were followed up until December 31st, 2009, collecting data on healthcare resource use and vital status.15857 patients were enrolled -9911 males, mean age: 76 years (SD 10. Over a mean follow-up time of 2.4 years (1.36, 81% of patients had at least one E-COPD with an annual rate of 3.2 exacerbations per person-year and an all-cause mortality of 47%. A history of exacerbation influenced the occurrence of new E-COPD and mortality after discharge for an E-COPD. On average, the healthcare system spent 6725€ per year per person (95%CI 6590-6863. Occurrence and type of exacerbations drove the direct healthcare cost. Less than one quarter of patients presented claims for pulmonary function tests.COPD imposes a substantial burden on healthcare systems, mainly attributable to the type and occurrence of E-COPD, or in other words, to the exacerbator phenotypes. A more tailored approach to the management of COPD patients is required.

  5. IL-33–Dependent Type 2 Inflammation during Rhinovirus-induced Asthma Exacerbations In Vivo

    OpenAIRE

    Jackson, David J.; Makrinioti, Heidi; Rana, Batika M. J.; Shamji, Betty W.H.; Trujillo-Torralbo, Maria-Belen; Footitt, Joseph; Jerico del-Rosario,; Telcian, Aurica G.; Nikonova, Alexandra; Zhu, Jie; Aniscenko, Julia; Gogsadze, Leila; Bakhsoliani, Eteri; Traub, Stephanie; Dhariwal, Jaideep

    2014-01-01

    Rationale: Rhinoviruses are the major cause of asthma exacerbations; however, its underlying mechanisms are poorly understood. We hypothesized that the epithelial cell–derived cytokine IL-33 plays a central role in exacerbation pathogenesis through augmentation of type 2 inflammation.

  6. Genetic variation in BAFF and asthma exacerbations among African American individuals

    Science.gov (United States)

    Kumar, Rajesh; Williams, L. Keoki; Kato, Atsushi; Peterson, Edward L.; Favoreto, Silvio; Hulse, Katie; Wang, Deli; Beckman, Kenneth; Thyne, Shannon; LeNoir, Michael; Meade, Kelley; Lanfear, David E.; Levin, Albert M.; Favro, David; Yang, James J.; Weiss, Kevin; Boushey, Homer A.; Grammer, Leslie; Avila, Pedro C; Burchard, Esteban G.; Schleimer, Robert

    2012-01-01

    Capsule Summary A BAFF polymorphism is associated with asthma exacerbations and serum BAFF levels. BAFF expression in vivo increases in natural rhinovirus infection. BAFF may play a role in airway antiviral immunity and impact asthma exacerbation rates. PMID:22728080

  7. Nav Channels in Damaged Membranes.

    Science.gov (United States)

    Morris, C E; Joos, B

    2016-01-01

    Sick excitable cells (ie, Nav channel-expressing cells injured by trauma, ischemia, inflammatory, and other conditions) typically exhibit "acquired sodium channelopathies" which, we argue, reflect bleb-damaged membranes rendering their Nav channels "leaky." The situation is excitotoxic because untreated Nav leak exacerbates bleb damage. Fast Nav inactivation (a voltage-independent process) is so tightly coupled, kinetically speaking, to the inherently voltage-dependent process of fast activation that when bleb damage accelerates and thus left-shifts macroscopic fast activation, fast inactivation accelerates to the same extent. The coupled g(V) and availability(V) processes and their window conductance regions consequently left-shift by the same number of millivolts. These damage-induced hyperpolarizing shifts, whose magnitude increases with damage intensity, are called coupled left shift (CLS). Based on past work and modeling, we discuss how to test for Nav-CLS, emphasizing the virtue of sawtooth ramp clamp. We explain that it is the inherent mechanosensitivity of Nav activation that underlies Nav-CLS. Using modeling of excitability, we show the known process of Nav-CLS is sufficient to predict a wide variety of "sick excitable cell" phenomena, from hyperexcitability through to depolarizing block. When living cells are mimicked by inclusion of pumps, mild Nav-CLS produces a wide array of burst phenomena and subthreshold oscillations. Dynamical analysis of mild damage scenarios shows how these phenomena reflect changes in spike thresholds as the pumps try to counteract the leaky Nav channels. Smart Nav inhibitors designed for sick excitable cells would target bleb-damaged membrane, buying time for cell-mediated removal or repair of Nav-bearing membrane that has become bleb-damaged (ie, detached from the cytoskeleton). PMID:27586295

  8. Aspirin-exacerbated respiratory disease: pathophysiological insights and clinical advances

    Directory of Open Access Journals (Sweden)

    Steinke JW

    2016-03-01

    Full Text Available John W Steinke, Jeff M Wilson Asthma and Allergic Disease Center, Carter Immunology Center, Department of Medicine, University of Virginia Health System, Charlottesville, VA, USA Abstract: Asthma and chronic rhinosinusitis are heterogeneous airway diseases of the lower and upper airways, respectively. Molecular and cellular studies indicate that these diseases can be categorized into unique endotypes, which have therapeutic implications. One such endotype is aspirin-exacerbated respiratory disease (AERD, which encompasses the triad of asthma, aspirin (or nonsteroidal anti-inflammatory drug hypersensitivity, and nasal polyposis. AERD has unique pathophysiological features that distinguish it from aspirin-tolerant asthma and other forms of chronic rhinosinusitis. This review details molecular and cellular features of AERD and highlights current and future therapies that are based on these insights. Keywords: leukotriene, cyclooxygenase, prostaglandin, aspirin-exacerbated respiratory disease, arachidonic acid

  9. Genetic Mechanisms in Aspirin-Exacerbated Respiratory Disease

    OpenAIRE

    Nami Shrestha Palikhe; Seung-Hyun Kim; Hyun Jung Jin; Eui-Kyung Hwang; Young Hee Nam; Hae-Sim Park

    2011-01-01

    Aspirin-exacerbated respiratory disease (AERD) refers to the development of bronchoconstriction in asthmatics following the exposure to aspirin or other nonsteroidal anti-inflammatory drugs. The key pathogenic mechanisms associated with AERD are the overproduction of cysteinyl leukotrienes (CysLTs) and increased CysLTR1 expression in the airway mucosa and decreased lipoxin and PGE2 synthesis. Genetic studies have suggested a role for variability of genes in disease susceptibility and the resp...

  10. Stress Exacerbates Neuropathic Pain via Glucocorticoid and NMDA Receptor Activation

    OpenAIRE

    Alexander, Jessica K.; DeVries, A. Courtney; KIGERL, KRISTINA A.; Dahlman, Jason M.; G.Popovich, Phillip

    2009-01-01

    There is growing recognition that psychological stress influences pain. Hormones that comprise the physiological response to stress (e.g. corticosterone; CORT) may interact with effectors of neuropathic pain. To test this hypothesis, mice received a spared nerve injury (SNI) after exposure to 60 min restraint stress. In stressed mice, allodynia was consistently increased. The mechanism(s) underlying the exacerbated pain response involves CORT acting via glucocorticoid receptors (GRs); RU486, ...

  11. Oxygen therapy in acute exacerbations of chronic obstructive pulmonary disease

    OpenAIRE

    Wedzicha, Wisia

    2014-01-01

    Simon E Brill, Jadwiga A Wedzicha Airway Disease Section, National Heart and Lung Institute, Imperial College, London, UK Abstract: Acute exacerbations of chronic obstructive pulmonary disease (COPD) are important events in the history of this debilitating lung condition. Associated health care utilization and morbidity are high, and many patients require supplemental oxygen or ventilatory support. The last 2 decades have seen a substantial increase in our understanding of the best way to ma...

  12. L-Arginine Pathway in COPD Patients with Acute Exacerbation

    DEFF Research Database (Denmark)

    Ruzsics, Istvan; Nagy, Lajos; Keki, Sandor; Sarosi, Veronika; Illes, Balazs; Illes, Zsolt; Horvath, Ildiko; Bogar, Lajos; Molnar, Tihamer

    BACKGROUND: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) remains a major cause of mortality. Clinical criteria of AECOPD are subjective. Biomarkers for AECOPD may aid in the initiation of early treatment. Increased production of asymmetric and symmetric dimethylarginine (A......-arginine, ADMA and SDMA serum levels. In patients with AECOPD, production of ADMA and SDMA are more pronounced presumably due to more severe hypoxic insult. Methylated arginine derivatives in the sera may help early recognition of AECOPD....

  13. Does aspirin-induced oxidative stress cause asthma exacerbation?

    OpenAIRE

    Kacprzak, Dorota; Pawliczak, Rafał

    2015-01-01

    Aspirin-induced asthma (AIA) is a distinct clinical syndrome characterized by severe asthma exacerbations after ingestion of aspirin or other non-steroidal anti-inflammatory drugs. The exact pathomechanism of AIA remains unknown, though ongoing research has shed some light. Recently, more and more attention has been focused on the role of aspirin in the induction of oxidative stress, especially in cancer cell systems. However, it has not excluded the similar action of aspirin in other inflamm...

  14. Inflamed psoriatic plaques: Drug toxicity or disease exacerbation?

    Directory of Open Access Journals (Sweden)

    Nidhi Jindal

    2013-01-01

    Full Text Available We are presenting a case of Methotrexate treated stable plaque psoriasis, in whom inflamed psoriatic plaques of drug toxicity were misdiagnosed as disease exacerbation. Erosive psoriatic plaques were present in the absence of biochemical or hematological derangements. Ulceration of psoriatic plaques in the presence of disturbed hematological profile is well described as a harbinger of methotrexate toxicity, but this kind of erosions in the absence of any systemic involvement is the first report of its kind.

  15. Comment je previens...une exacerbation de la dermatite atopique.

    OpenAIRE

    Xhauflaire, Emmanuelle; Pierard, Claudine; Nikkels, Arjen; Pierard, Gérald

    2006-01-01

    Atopic dermatitis is under the influence of series of environmental factors. The contact with unsuited cleaning agents and rough textiles can exacerbate pruritus and inflammation. Preventive and adjuvant measures can thus help the care procedures of the disease. Appropriate hygiene measures and the use of emollients are particularly helpful. Clothing measures are also in place. Undergarments and pyjamas made of knitted natural silk are available. Other measures, sometimes corresponding to ane...

  16. Relationship between frequency, length, and treatment outcome of exacerbations to baseline lung function and lung density in alpha-1 antitrypsin-deficient COPD

    Directory of Open Access Journals (Sweden)

    Vijayasaratha K

    2012-11-01

    Full Text Available Kesavaperumal Vijayasaratha,1 Robert A Stockley21Lung Investigation Unit, 2Research and Development, University Hospital Birmingham NHS Trust, Birmingham, UKBackground: Diary cards are useful for analyzing exacerbations in chronic obstructive pulmonary disease (COPD, although factors influencing the length and frequency of each episode are poorly understood. This study investigated factors that influence the features of exacerbations in patients with alpha-1 antitrypsin (AAT deficiency (PiZ phenotype and COPD.Methods: Daily diary cards were collected over 2 years. Patients had emphysema visualized and quantified by computed tomography scan, and had at least one documented exacerbation in the previous year.Results: The patients (n = 23 had a mean age of 52.5 years, forced expiratory volume in one second (FEV1 of 1.2 L (38.4% predicted, corrected gas transfer (KCO of 0.90 mmol/min/kPa/L (59.7% predicted, and 15th percentile lung density of 44.55 g/L. Two hundred and sixty-three exacerbations (164 treated were identified. The frequency of treated exacerbations correlated negatively with KCO% predicted (r = −0.432; P = 0.022. Exacerbation length (determined for 17 of the patients for whom diary card data through the episode were available correlated negatively with baseline 15th percentile lung density (r = −0.361; P = 0.003, and increased the longer treatment was delayed (r = 0.503; P < 0.001. Treatment delay was shorter with higher day 1 symptom score, lower baseline FEV1, FEV1/forced vital capacity, and lower 15th percentile lung density (r = −0.368, 0.272, 0.461, and 0.786; P = 0.004, 0.036, <0.001, and <0.001, respectively. Time to resolution of exacerbation after treatment initiation was not affected by treatment delay, but correlated negatively with KCO% predicted (r = −0.647; P = 0.007.Conclusion: In alpha-1 antitrypsin deficiency, the frequency and length of resolution of exacerbation were related to baseline gas transfer. Treatment

  17. Corticosteroids in the treatment of acute exacerbations of chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Woods JA

    2014-05-01

    Full Text Available J Andrew Woods,1 James S Wheeler,1 Christopher K Finch,2 Nathan A Pinner3 1School of Pharmacy, Wingate University, Wingate, NC, USA; 2Department of Pharmacy, Methodist University Hospital, Memphis, TN, USA; 3Harrison School of Pharmacy, Auburn University, Auburn, AL, USA Background: Chronic obstructive pulmonary disease (COPD is a chronic and progressive disease that affects an estimated 10% of the world's population over the age of 40 years. Worldwide, COPD ranks in the top ten for causes of disability and death. Given the significant impact of this disease, it is important to note that acute exacerbations of COPD (AECOPD are by far the most costly and devastating aspect of disease management. Systemic steroids have long been a standard for the treatment of AECOPD; however, the optimal strategy for dosing and administration of these medications continues to be debated. Objective: To review the use of corticosteroids in the treatment of acute exacerbations of COPD. Materials and methods: Literature was identified through PubMed Medline (1950–February 2014 and Embase (1950–February 2014 utilizing the search terms corticosteroids, COPD, chronic bronchitis, emphysema, and exacerbation. All reference citations from identified publications were reviewed for possible inclusion. All identified randomized, placebo-controlled trials, meta-analyses, and systematic reviews evaluating the efficacy of systemic corticosteroids in the treatment of AECOPD were reviewed and summarized. Results: The administration of corticosteroids in the treatment of AECOPD was assessed. In comparison to placebo, systemic corticosteroids improve airflow, decrease the rate of treatment failure and risk of relapse, and may improve symptoms and decrease the length of hospital stay. Therefore, corticosteroids are recommended by all major guidelines in the treatment of AECOPD. Existing literature suggests that low-dose oral corticosteroids are as efficacious as high

  18. Computerised Analysis of Telemonitored Respiratory Sounds for Predicting Acute Exacerbations of COPD

    Directory of Open Access Journals (Sweden)

    Miguel Angel Fernandez-Granero

    2015-10-01

    Full Text Available Chronic obstructive pulmonary disease (COPD is one of the commonest causes of death in the world and poses a substantial burden on healthcare systems and patients’ quality of life. The largest component of the related healthcare costs is attributable to admissions due to acute exacerbation (AECOPD. The evidence that might support the effectiveness of the telemonitoring interventions in COPD is limited partially due to the lack of useful predictors for the early detection of AECOPD. Electronic stethoscopes and computerised analyses of respiratory sounds (CARS techniques provide an opportunity for substantial improvement in the management of respiratory diseases. This exploratory study aimed to evaluate the feasibility of using: (a a respiratory sensor embedded in a self-tailored housing for ageing users; (b a telehealth framework; (c CARS and (d machine learning techniques for the remote early detection of the AECOPD. In a 6-month pilot study, 16 patients with COPD were equipped with a home base-station and a sensor to daily record their respiratory sounds. Principal component analysis (PCA and a support vector machine (SVM classifier was designed to predict AECOPD. 75.8% exacerbations were early detected with an average of 5 ± 1.9 days in advance at medical attention. The proposed method could provide support to patients, physicians and healthcare systems.

  19. Computerised Analysis of Telemonitored Respiratory Sounds for Predicting Acute Exacerbations of COPD.

    Science.gov (United States)

    Fernandez-Granero, Miguel Angel; Sanchez-Morillo, Daniel; Leon-Jimenez, Antonio

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) is one of the commonest causes of death in the world and poses a substantial burden on healthcare systems and patients' quality of life. The largest component of the related healthcare costs is attributable to admissions due to acute exacerbation (AECOPD). The evidence that might support the effectiveness of the telemonitoring interventions in COPD is limited partially due to the lack of useful predictors for the early detection of AECOPD. Electronic stethoscopes and computerised analyses of respiratory sounds (CARS) techniques provide an opportunity for substantial improvement in the management of respiratory diseases. This exploratory study aimed to evaluate the feasibility of using: (a) a respiratory sensor embedded in a self-tailored housing for ageing users; (b) a telehealth framework; (c) CARS and (d) machine learning techniques for the remote early detection of the AECOPD. In a 6-month pilot study, 16 patients with COPD were equipped with a home base-station and a sensor to daily record their respiratory sounds. Principal component analysis (PCA) and a support vector machine (SVM) classifier was designed to predict AECOPD. 75.8% exacerbations were early detected with an average of 5 ± 1.9 days in advance at medical attention. The proposed method could provide support to patients, physicians and healthcare systems. PMID:26512667

  20. Diabetes and ageing-induced vascular inflammation.

    Science.gov (United States)

    Assar, Mariam El; Angulo, Javier; Rodríguez-Mañas, Leocadio

    2016-04-15

    Diabetes and the ageing process independently increase the risk for cardiovascular disease (CVD). Since incidence of diabetes increases as people get older, the diabetic older adults represent the largest population of diabetic subjects. This group of patients would potentially be threatened by the development of CVD related to both ageing and diabetes. The relationship between CVD, ageing and diabetes is explained by the negative impact of these conditions on vascular function. Functional and clinical evidence supports the role of vascular inflammation induced by the ageing process and by diabetes in vascular impairment and CVD. Inflammatory mechanisms in both aged and diabetic vasculature include pro-inflammatory cytokines, vascular hyperactivation of nuclear factor-кB, increased expression of cyclooxygenase and inducible nitric oxide synthase, imbalanced expression of pro/anti-inflammatory microRNAs, and dysfunctional stress-response systems (sirtuins, Nrf2). In contrast, there are scarce data regarding the interaction of these mechanisms when ageing and diabetes co-exist and its impact on vascular function. Older diabetic animals and humans display higher vascular impairment and CVD risk than those either aged or diabetic, suggesting that chronic low-grade inflammation in ageing creates a vascular environment favouring the mechanisms of vascular damage driven by diabetes. Further research is needed to determine the specific inflammatory mechanisms responsible for exacerbated vascular impairment in older diabetic subjects in order to design effective therapeutic interventions to minimize the impact of vascular inflammation. This would help to prevent or delay CVD and the specific clinical manifestations (cognitive decline, frailty and disability) promoted by diabetes-induced vascular impairment in the elderly. PMID:26435167

  1. Parkinson's disease brain mitochondria have impaired respirasome assembly, age-related increases in distribution of oxidative damage to mtDNA and no differences in heteroplasmic mtDNA mutation abundance

    Directory of Open Access Journals (Sweden)

    Keeney Paula M

    2009-09-01

    Full Text Available Abstract Background Sporadic Parkinson's disease (sPD is a nervous system-wide disease that presents with a bradykinetic movement disorder and is frequently complicated by depression and cognitive impairment. sPD likely has multiple interacting causes that include increased oxidative stress damage to mitochondrial components and reduced mitochondrial bioenergetic capacity. We analyzed mitochondria from postmortem sPD and CTL brains for evidence of oxidative damage to mitochondrial DNA (mtDNA, heteroplasmic mtDNA point mutations and levels of electron transport chain proteins. We sought to determine if sPD brains possess any mtDNA genotype-respiratory phenotype relationships. Results Treatment of sPD brain mtDNA with the mitochondrial base-excision repair enzyme 8-oxyguanosine glycosylase-1 (hOGG1 inhibited, in an age-dependent manner, qPCR amplification of overlapping ~2 kbase products; amplification of CTL brain mtDNA showed moderate sensitivity to hOGG1 not dependent on donor age. hOGG1 mRNA expression was not different between sPD and CTL brains. Heteroplasmy analysis of brain mtDNA using Surveyor nuclease® showed asymmetric distributions and levels of heteroplasmic mutations across mtDNA but no patterns that statistically distinguished sPD from CTL. sPD brain mitochondria displayed reductions of nine respirasome proteins (respiratory complexes I-V. Reduced levels of sPD brain mitochondrial complex II, III and V, but not complex I or IV proteins, correlated closely with rates of NADH-driven electron flow. mtDNA levels and PGC-1α expression did not differ between sPD and CTL brains. Conclusion PD brain mitochondria have reduced mitochondrial respiratory protein levels in complexes I-V, implying a generalized defect in respirasome assembly. These deficiencies do not appear to arise from altered point mutational burden in mtDNA or reduction of nuclear signaling for mitochondrial biogenesis, implying downstream etiologies. The origin of age

  2. Identification of preadmission predictors of outcome of noninvasive ventilation in acute exacerbation of chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Shameem Mohd.

    2005-01-01

    Full Text Available Background: Noninvasive ventilation (NIV has been shown to be an effective treatment for ventilatory failure, particularly resulting from acute exacerbations of chronic obstructive pulmonary disease (COPD. However, NIV is associated with significant failure rates. Hence, there is a need for identifying preadmission predictors for outcome of NIV in patients for acute exacerbation of COPD, thereby sparing the discomfort of a trial of NIV on these patients. Aim: The study was carried to identify the preadmission predictors of outcome of NIV in acute exacerbation of COPD with respiratory failure. Material and Methods: The study was carried in the Department of TB & Chest diseases at the Jawaharlal Nehru Medical College, AMU; 250 patients with acute exacerbation of COPD were enrolled in the study. These patients were grouped on the basis of six different independent variables, viz. age, performance status, pH, late failures, SaO2, and presence or absence of pedal edema. Analysis was done by z-test, P Observation: Age had no impact on the outcome of patient on NIV ( z = 0.3.The risk for endotracheal intubation was found to be increased by the presence of pedal edema ( z = 6.2; P < 0.001, O2 saturation of less than 86% ( z = 4.7; P < 0.001, and acidemia (pH < 7.3 on admission ( z = 10.6; P < 0.001. In addition, poor performance status of limited self-care ( z = 3.2; P < 0.01 and late failures carried poor outcome of NIV ( z = 8.3; P < 0.001. Conclusion: Patients′ COPD with poor baseline performance status, pedal edema, low oxygen saturation, and academia carry a high likelihood of failure and should be spared a prolonged trial of NIV.

  3. Mechanisms of Diabetes-Induced Liver Damage

    Science.gov (United States)

    Mohamed, Jamaludin; Nazratun Nafizah, A. H.; Zariyantey, A. H.; Budin, S. B.

    2016-01-01

    Diabetes mellitus is a non-communicable disease that occurs in both developed and developing countries. This metabolic disease affects all systems in the body, including the liver. Hyperglycaemia, mainly caused by insulin resistance, affects the metabolism of lipids, carbohydrates and proteins and can lead to non-alcoholic fatty liver disease, which can further progress to non-alcoholic steatohepatitis, cirrhosis and, finally, hepatocellular carcinomas. The underlying mechanism of diabetes that contributes to liver damage is the combination of increased oxidative stress and an aberrant inflammatory response; this activates the transcription of pro-apoptotic genes and damages hepatocytes. Significant involvement of pro-inflammatory cytokines—including interleukin (IL)-1β, IL-6 and tumour necrosis factor-α—exacerbates the accumulation of oxidative damage products in the liver, such as malondialdehyde, fluorescent pigments and conjugated dienes. This review summarises the biochemical, histological and macromolecular changes that contribute to oxidative liver damage among diabetic individuals. PMID:27226903

  4. Damage Distributions

    DEFF Research Database (Denmark)

    Lützen, Marie

    2001-01-01

    The purpose of Task 2.2 of the HARDER project is according to the work package description: For various structural configurations of the struck ship and using the results of Task 2.1, the probability distributions for the damage location and size will be derived. The format will be similar to the...... damage statistics and bow height statistics for vessels in the world fleet. The proposals for the p-, r-, and v-factors have been compared to factors from current regulation by examples.......The purpose of Task 2.2 of the HARDER project is according to the work package description: For various structural configurations of the struck ship and using the results of Task 2.1, the probability distributions for the damage location and size will be derived. The format will be similar to the p...... between the damage location, the damage sizes and the main particulars of the struck vessel. From the numerical simulation and the analyse of the damage statistics it is found that the current formulation from the IMO SLF 43/3/2 can be used as basis for determination of the p-, r-, and v...

  5. Age and organ damage correlate with poor survival in myeloma patients: meta-analysis of 1435 individual patient data from 4 randomized trials.

    Science.gov (United States)

    Bringhen, Sara; Mateos, Maria Victoria; Zweegman, Sonja; Larocca, Alessandra; Falcone, Antonietta Pia; Oriol, Albert; Rossi, Davide; Cavalli, Maide; Wijermans, Pierre; Ria, Roberto; Offidani, Massimo; Lahuerta, Juan Jose; Liberati, Anna Marina; Mina, Roberto; Callea, Vincenzo; Schaafsma, Martijn; Cerrato, Chiara; Marasca, Roberto; Franceschini, Luca; Evangelista, Andrea; Teruel, Ana-Isabel; van der Holt, Bronno; Montefusco, Vittorio; Ciccone, Giovannino; Boccadoro, Mario; San Miguel, Jesus; Sonneveld, Pieter; Palumbo, Antonio

    2013-06-01

    Thalidomide and bortezomib are extensively used to treat elderly myeloma patients. In these patients, treatment-related side effects are frequent and full drug doses difficult to tolerate. We retrospectively analyzed data from 1435 elderly patients enrolled in 4 European phase III trials including thalidomide and/or bortezomib. After a median follow up of 33 months (95%CI: 10-56 months), 513 of 1435 patients (36%) died; median overall survival was 50 months (95%CI: 46-60 months). The risk of death was increased in patients aged 75 years or over (HR 1.44, 95%CI: 1.20-1.72; Pthalidomide, negatively affected outcome. Bortezomib-based combinations may overcome the negative impact of renal failure. Age 75 years or over or renal failure at presentation, occurrence of infections, cardiac or gastrointestinal adverse events negatively affected survival. A detailed geriatric assessment, organ evaluation and less intense individualized approaches are suggested in elderly unfit subjects. PMID:23445873

  6. High-flow nasal cannula oxygen therapy for acute exacerbation of interstitial pneumonia: A case series.

    Science.gov (United States)

    Horio, Yukihiro; Takihara, Takahisa; Niimi, Kyoko; Komatsu, Masamichi; Sato, Masako; Tanaka, Jun; Takiguchi, Hiroto; Tomomatsu, Hiromi; Tomomatsu, Katsuyoshi; Hayama, Naoki; Oguma, Tsuyoshi; Aoki, Takuya; Urano, Tetsuya; Takagi, Atsushi; Asano, Koichiro

    2016-03-01

    We report 3 cases (all men, age: 69-81 years) of acute exacerbation of interstitial pneumonia (AEIP) that were successfully treated with a high-flow nasal cannula (HFNC), which delivers heated, humidified gas at a fraction of inspired oxygen (FIO2) up to 1.0 (100%). Oxygenation was insufficient under non-rebreathing face masks; however, the introduction of HFNC with an FIO2 of 0.7-1.0 (flow rate: 40L/min) improved oxygenation and was well-tolerated until the partial pressure of oxygen in blood/FIO2 ratio increased (between 21 and 26 days). Thus, HFNC might be an effective and well-tolerated therapeutic addition to the management of AEIP. PMID:26879483

  7. Incidence and outcomes of patients hospitalized with COPD exacerbation with and without pneumonia

    Directory of Open Access Journals (Sweden)

    Søgaard M

    2016-03-01

    Full Text Available Mette Søgaard,1 Morten Madsen,1 Anders Løkke,2 Ole Hilberg,2 Henrik Toft Sørensen,1 Reimar W Thomsen1 1Department of Clinical Epidemiology, 2Department of Respiratory Medicine, Aarhus University Hospital, Aarhus C, Denmark Background: Pneumonia may be a major contributor to hospitalizations for chronic obstructive pulmonary disease (COPD exacerbation and influence their outcomes.Methods: We examined hospitalization rates, health resource utilization, 30-day mortality, and risk of subsequent hospitalizations for COPD exacerbations with and without pneumonia in Denmark during 2006–2012.Results: We identified 179,759 hospitalizations for COPD exacerbations, including 52,520 first-time hospitalizations (29.2%. Pneumonia was frequent in first-time exacerbations (36.1%, but declined in successive exacerbations to 25.6% by the seventh or greater exacerbation. Pneumonic COPD exacerbations increased 20% from 0.92 per 1,000 population in 2006 to 1.10 per 1,000 population in 2012. Nonpneumonic exacerbations decreased by 6% from 1.74 per 1,000 population to 1.63 per 1,000 population during the same period. A number of markers of health resource utilization were more prevalent in pneumonic exacerbations than in nonpneumonic exacerbations: length of stay (median 7 vs 4 days, intensive care unit admission (7.7% vs 12.5%, and several acute procedures. Thirty-day mortality was 12.1% in first-time pneumonic COPD exacerbations versus 8.3% in first-time nonpneumonic cases (adjusted HR [aHR] 1.20, 95% confidence interval [CI] 1.17–1.24. Pneumonia also predicted increased mortality associated with a second exacerbation (aHR 1.14, 95% CI 1.11–1.18, and up to a seventh or greater exacerbation (aHR 1.10, 95% CI 1.07–1.13. In contrast, the aHR of a subsequent exacerbation was 8%–13% lower for patients with pneumonic exacerbations.Conclusions: Pneumonia is frequent among patients hospitalized for COPD exacerbations and is associated with increased health care

  8. Antibiotic treatment of exacerbations of COPD in general practice: long-term impact on healthrelated quality of life

    Directory of Open Access Journals (Sweden)

    Marc Miravitlles

    2010-01-01

    Full Text Available Marc Miravitlles1, Carles Llor2, Jesús Molina3, Karlos Naberan4, Josep M Cots5, Fernando Ros6 on behalf of the EVOCA Study Group1Fundació Clínic. Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS, Hospital Clínic, Ciber de Enfermedades Respiratorias (CIBERES, Barcelona, Spain; 2Primary Health Care Center ‘Jaume I’, Societat Catalana de Medicina Familiar i Comunitària, Universitat Rovira i Virgili, Tarragona, Spain; 3Primary Health Care Center ‘Francia’, Grupo de Respiratorio de la Sociedad Madrileña de Medicina Familiar y Comunitaria, Madrid, Spain; 4Primary Health Care Center ‘Fuentes de Ebro’, Grupo de Investigación del Instituto Aragonés Ciencias de la Salud (IACS, Zaragoza, Spain; 5Primary Health Care Center ‘La Marina’, Societat Catalana de Medicina Familiar i Comunitària, Facultat de Medicina, Barcelona, Spain; 6Medical Department, Bayer Healthcare, Barcelona, SpainObjective: To investigate the impact of exacerbations in health-related quality of life (HRQL of patients with COPD and to compare the effect of treatment of COPD exacerbations with moxifloxacin (400 mg/day for 5 days and amoxicillin/clavulanate (500/125 mg 3 times a day for 10 days on HRQL.Methods: 229 outpatients with stable COPD (mean age 68.2 years; mean FEV1 % predicted 49.3% participated in a prospective, observational study of 2 years’ duration. The St George’s Respiratory Questionnaire (SGRQ was completed at baseline and every 6 months thereafter.Results: COPD exacerbations (mean 2.7 episodes/patient occurred in 136 patients (124 patients received the study medications [amoxicillin/clavulanate 54, moxifloxacin 70]. Differences between baseline and the final visit were higher for moxifloxacin compared with amoxicillin/clavulanate for total SGRQ score (-2.60 [13.1] vs 4.21 [16.2], P = 0.05 and “Symptoms” subscale (-5.64 [16.7] vs 8.27 [21], P = 0.02. The same findings were observed in patients with two or more

  9. Management of chronic obstructive pulmonary disease exacerbations in Internal Medicine

    Directory of Open Access Journals (Sweden)

    Gelorma Belmonte

    2013-03-01

    Full Text Available Introduction: Chronic obstructive pulmonary disease (COPD is the second leading cause of hospitalization in Internal Medicine departments in Italy and the fourth leading cause of death all over the word. By 2020, COPD will be the third leading cause of death and the fifth leading cause of disability. It is — along with chronic congestive heart failure — one of the most common causes of unscheduled hospital readmissions, and as such it represents a significant economic burden for the health-care system. Exacerbations of COPD are important events in the natural history of this prevalent condition. Discussion: This review provides a comprehensive state-of-the-art look at prevention and management of COPD exacerbations. Treatment of these episodes has to be tailored to the severity of the clinical presentation. We now have a wide range of therapeutic available options, based on the results of clinical trials. Management of the acute event should include the necessary measures (mainly the administration of inhaled short-acting bronchodilators, inhaled or oral corticosteroids, and antibiotics, with or without oxygen and ventilator support. Conclusions: To improve the management of COPD exacerbations, the focus of care must be shifted from the episodic acute complications to their systematic prevention. The management of COPD, which is often associated with multiple co-morbidities, is complex and requires a tailored, multifaceted and multidisciplinary approach. Integrated care for COPD also requires that patients be informed about their condition, that they participate actively in their care, and that they have easy access to the necessary health-care services.

  10. ROLE OF ORAL MONTELUKAST IN ACUTE ASTHMA EXACERBATIONS : A RANDOMIZED PLACEBO CONTROLLED TRIAL

    Directory of Open Access Journals (Sweden)

    Gaude

    2015-08-01

    Full Text Available BACKGROUND: Leukotriene receptor antagonists (LTRAs are well established in the management of outpatient asthma. However, there is very little information as to their role in acute asthma exacerbations. The present study was done to evaluate the clinical efficacy of oral Montelukast as an add on therapy to the usual standard therapy of acute attack of bronchial asthma. MATERIALS AND METHODS: A randomized single blinded controlled study was conducted in a tertiary car e teaching hospital. A total of 320 patients with age >18 years of acute exacerbations due to bronchial asthma were included in the study. The patients were randomized into two study and control groups. The study group patients received oral Montelukast (1 0mg once daily for 2 weeks, while the control group received a placebo. All the patients received standard therapy according to GINA guidelines. Improvements in lung function tests, clinical symptoms and relapse rates were monitored at baseline, at discha rge and at 2 weeks. Side effects profile was also monitored. RESULTS: A total of 255 patients were finally assessed. One hundred thirty patients belonged to study group and 125 in the control group. Baseline characteristics were similar and well matched in both the groups. Mean age was 39.9±15.8 years in study group and 42.8±12.8 in the control group and majority were female patients in both the groups. At the end of 2 weeks, it was observed that there were no significant improvements in FEV 1 and FVC as com pared to the control group. However, there was significant improvement in PEFR at 2 weeks (0.4 L/sec, 12% as compared to the control group (p <0.0376. Length of hospital stay was similar in both the groups. No serious adverse effects were noted during th e course of the study. CONCLUSIONS: In acute asthma exacerbations, the present study showed that additional administration of oral Montelukast resulted in significantly higher PEFR at 2 weeks as compared to the standard

  11. Update on the Management of Aspirin-Exacerbated Respiratory Disease.

    Science.gov (United States)

    Buchheit, Kathleen M; Laidlaw, Tanya M

    2016-07-01

    Aspirin-exacerbated respiratory disease (AERD) is an adult-onset upper and lower airway disease consisting of eosinophilic nasal polyps, asthma, and respiratory reactions to cyclooxygenase 1 (COX-1) inhibitors. Management includes guideline-based treatment of asthma and sinus disease, avoidance of COX-1 inhibitors, and for some patients aspirin desensitization followed by high-dose aspirin therapy. Despite this, many patients have inadequately controlled symptoms and require multiple sinus surgeries. In this review, we discuss the current standard approaches to the management of AERD, and we introduce several therapeutics under development that may hold promise for the treatment of AERD. PMID:27126722

  12. uPA deficiency exacerbates muscular dystrophy in MDX mice

    OpenAIRE

    Suelves, Mònica; Vidal, Berta; Serrano, Antonio L.; Tjwa, Marc; Roma, Josep; López-Alemany, Roser; Luttun, Aernout; de Lagrán, María Martínez; Díaz, Maria Àngels; Jardí, Mercè; Roig, Manuel; Dierssen, Mara; Dewerchin, Mieke; Carmeliet, Peter; Muñoz-Cánoves, Pura

    2007-01-01

    Duchenne muscular dystrophy (DMD) is a fatal and incurable muscle degenerative disorder. We identify a function of the protease urokinase plasminogen activator (uPA) in mdx mice, a mouse model of DMD. The expression of uPA is induced in mdx dystrophic muscle, and the genetic loss of uPA in mdx mice exacerbated muscle dystrophy and reduced muscular function. Bone marrow (BM) transplantation experiments revealed a critical function for BM-derived uPA in mdx muscle repair via three mechanisms: (...

  13. Aspirin-exacerbated respiratory disease: pathophysiological insights and clinical advances.

    Science.gov (United States)

    Steinke, John W; Wilson, Jeff M

    2016-01-01

    Asthma and chronic rhinosinusitis are heterogeneous airway diseases of the lower and upper airways, respectively. Molecular and cellular studies indicate that these diseases can be categorized into unique endotypes, which have therapeutic implications. One such endotype is aspirin-exacerbated respiratory disease (AERD), which encompasses the triad of asthma, aspirin (or nonsteroidal anti-inflammatory drug) hypersensitivity, and nasal polyposis. AERD has unique pathophysiological features that distinguish it from aspirin-tolerant asthma and other forms of chronic rhinosinusitis. This review details molecular and cellular features of AERD and highlights current and future therapies that are based on these insights. PMID:27022293

  14. 过氧化氢诱导的人正常和早老细胞中DNA损伤及其修复研究%The Study of Hydrogen Peroxide Induced DNA Damage and Recovery in Normal Aging and Premature Aging Human Cells

    Institute of Scientific and Technical Information of China (English)

    所起凤; 杜文婷; 杨鸣鸣; 范雪娇; 刘戟

    2011-01-01

    目的 研究人早老细胞和正常衰老细胞在氧化应激条件下的DNA损伤和修复.方法 采用免疫荧光技术和彗星电泳技术,分别检测3组不同群体倍增数(PD)的人正常二倍体成纤维细胞BJ(青年组第14代,成年组第30代,衰老组第45代)和2组不同PD的人赫-吉二氏综合征(HGPS)细胞(青年组第8代,衰老组第17代)的DNA基础损伤程度.研究过氧化氢诱导造成以上细胞组DNA损伤及去除致损因素正常培养后的修复水平,采用免疫荧光和彗星电泳技术检测细胞在沉默DNA损伤修复蛋白着色性干皮病蛋白A(XPA)表达前后的修复能力.结果 BJ细胞衰老组DNA损伤程度较高,与成年组相比,对DNA损伤诱导因子更加敏感(P<0.05);成年组与青年组相比,对损伤诱导因子也更敏感(P<0.05).HGPS细胞青年组的DNA基础损伤程度即已达到衰老BJ细胞类似或更高水平,且与BJ细胞具有一致的DNA损伤年龄变化趋势.经siRNA沉默XPA表达后可部分恢复HGPS细胞的修复能力,对BJ细胞则没有影响.随年龄增长无论正常还是早老细胞,DNA损伤程度增加,修复效率降低.结论 XPA功能异常抑制了HGPS细胞的损伤修复.%Objective To study the DNA damage and recovery induced by hydrogen peroxide in normal aging and premature aging human cells. Methods The immunofluorescent assay and comet assay were used to estimate basal DNA damage in normal aging BJ cells and premature aging Hutchinson-Gilford progeria syndrome (HGPS) cells, which were divided into three and two distinct population doubling (PD) number groups (BJ 14· 30, 45 and HGPS 8, 17) respectively. The DNA damage induced by hydrogen peroxide of these cell populations, as well as their repair activity, was also studied. Finally, the recovery capability before and after the xeroderma pigmentosum group A (XPA ) knocked down in these groups was measured. Results Our results indicated that the normal BJ cells of older PD number

  15. Association of disease activity with acute exacerbation of interstitial lung disease during tocilizumab treatment in patients with rheumatoid arthritis: a retrospective, case-control study.

    Science.gov (United States)

    Akiyama, Mitsuhiro; Kaneko, Yuko; Yamaoka, Kunihiro; Kondo, Harumi; Takeuchi, Tsutomu

    2016-06-01

    The objective of the study was to identify risk factors for acute exacerbation of interstitial lung disease (ILD) during tocilizumab treatment in patients with rheumatoid arthritis (RA). This is a retrospective, case-control study. We reviewed 395 consecutive RA patients who received tocilizumab. First, we divided the patients according to the presence (RA-ILD) or absence of ILD (non-ILD) assessed by chest X-ray or high-resolution computed tomography, and compared them for characteristics relevant to RA-ILD. Subsequently, focusing on the patients with RA-ILD, we assessed their baseline characteristics and clinical courses comparing patients with acute exacerbation to those without. Comparing 78 with ILD and 317 without ILD, the following were identified as factors related to RA-ILD on multivariate analysis: age 60 years or older (OR 4.5, 95 % CI 2.2-9.4, P smoking habit (OR 2.9, 95 % CI 1.5-5.5, P = 0.002), and high rheumatoid factor levels (OR 2.8, 95 % CI 1.4-5.5, P = 0.002). Of 78 RA-ILD patients, six developed acute exacerbation during tocilizumab treatment. The median duration between the initiation of tocilizumab treatment and the acute exacerbation occurrence was 48 weeks. While baseline characteristics did not differ between acute exacerbation and non-acute exacerbation groups, patients experiencing acute exacerbation had significantly higher Clinical Disease Activity Index (CDAI) at 24 weeks (20.8 vs. 6.2, P = 0.019). Univariate analysis showed that CDAI > 10 at 24 weeks was a risk factor for acute exacerbation (OR 4.7, 95 % CI 2.1-10.4, P = 0.02). Uncontrolled arthritis activity during tocilizumab treatment may be associated with acute exacerbation of RA-ILD, suggesting post-treatment monitoring of disease activity is important not only with respect to RA itself but also for RA-ILD. PMID:27072347

  16. Indoor damage of aged porous natural stone due to thermohygric stress: a case study of opuka stone altar from the St. Vitus Cathedral, Prague (Czech Republic)

    Science.gov (United States)

    Prikryl, Richard; Prikrylova, Jirina; Racek, Martin; Kreislova, Kateřina; Weishauptova, Zuzana

    2016-04-01

    Opuka stone (extremely fine-grained clayey-calcareous silicite) used for a carved stone altar located in the interior of the St. Vitus Cathedral (Prague, Czech Republic) was affected by decay phenomena (formation of the case-hardened surface, its later blistering, flaking and/or powdering of stone substrate) which are similar to those observed in outdoor environments. Through the detailed analytical study (optical microscopy and scanning electron microscopy with energy dispersive spectrometry and x-ray elemental mapping of cross-sections of surface layers, x-ray diffraction of surface layers, ion-exchange chromatography for water-soluble salts, mercury porosimetry) and analysis of long-term indoor environmental monitoring (temperature, relative humidity, sulphur and nitrogen oxides deposition), it has been found that observed decay phenomena, which are manifested on microscale by brittle damage and formation of mode I (tensile) cracks along the exposed surface of the stone, can be interpreted as a result from thermohygric stress occurring on the interface between case hardened surface layer and stone substrate.

  17. Strong exercise stress exacerbates dermatitis in atopic model mice, NC/Nga mice, while proper exercise reduces it.

    Science.gov (United States)

    Orita, Kumi; Hiramoto, Keiichi; Inoue, Risa; Sato, Eisuke F; Kobayashi, Hiromi; Ishii, Masamitsu; Inoue, Masayasu

    2010-12-01

    Atopic dermatitis is well known to exacerbate by stress. How the influence of exercise stress on the skin symptoms in patients with atopic dermatitis has not been clarified. The purpose of our research is to investigate how different strength of exercise stress acts on atopic dermatitis. Specific pathogen-free (SPF) and conventional NC/Nga male mice were used for the experiments. Conventional mice but not SPF group spontaneously develop dermal symptom similar to that of patients with atopic dermatitis at their age of 7 weeks. They were given two types of stress, mild (20 m/min for 60 min) or strong exercise (25 m/min for 90 min), using a treadmill four times per day. The dermal symptom of the conventional group was strongly exacerbated by strong exercise but ameliorated by mild exercise. Under the standard experimental conditions, plasma concentrations of α-melanocyte-stimulating hormone (α-MSH), transforming growth factor-β (TGF-β) and substance P in conventional mice increased markedly with concomitant exacerbation of the symptom. The plasma concentrations of these proteins elevated after strong exercise but decreased after mild exercise. Under the conventional conditions, plasma levels of β-endorphin increased with time by some mechanisms enhanced by the mild exercise. These observations suggested that exercise-induced stress significantly affect the symptom of atopic dermatitis in a pivotal manner depending on the plasma levels of TGF-β, α-MSH, substance P and β-endorphin. PMID:21087324

  18. Frequency of Streptococcus pneumonia and Haemophilus influenza in acute exacerbation of chronic obstructive airway disease and their sensitivity to levofloxacin

    International Nuclear Information System (INIS)

    Objective: To determine the frequency of Streptococcus pneumoniae and Haemophilus influenzae in acute exacerbation of chronic obstructive pulmonary disease and their sensitivity to levofloxacin. Methods: The cross-sectional study was conducted at the Department of Medicine, AbbasiShaheed Hospital, Karachi, between July 2009 and January 2010. Patients already diagnosed with chronic obstructive pulmonary disease and admitted with symptoms of acute exacerbation were included in the study and their sputum samples were sent for microbiological evaluation. SPSS 16 was used for statistical analysis. Results: Of the total 105 patients in the study, 90 (85.17%) were males. Overall mean age at presentation was 62+-10.2 years. S. pneumoniae was isolated from sputum culture of 33 (31.4%) patients, while 13 (12.4%) patients showed growth of H. influenzae. Out of the 33 sputum specimens of S. pneumoniae, 32 (97.0%) were sensitive to levofloxacin, while 1 (3.0%) was resistant. All the 13 isolates of H. influenzae were sensitive to levofloxacin. Conclusion: S. pneumoniae and H. influenzae are still the most prevalent organisms isolated in acute exacerbation of chronic obstructive pulmonary disease in our population. Levofloxacin is still considered a highly sensitive antibiotic against these common micro-organisms in our population, but S. pneumoniae has started developing resistance against levofloxacin. Therefore, intermittent surveillance regarding development of resistance pattern of common micro-organisms against commonly prescribed antibiotics is required. (author)

  19. DAMPs-activated neutrophil extracellular trap exacerbates sterile inflammatory liver injury

    Science.gov (United States)

    Huang, Hai; Tohme, Samer; Al-Khafaji, Ahmed B; Tai, Sheng; Loughran, Patricia; Chen, Li; Wang, Shu; Kim, Jiyun; Billiar, Timothy; Wang, Yanming; Tsung, Allan

    2015-01-01

    Innate immunity plays a crucial role in the response to sterile inflammation such as liver ischemia/reperfusion (I/R) injury. The initiation of liver I/R injury results in the release of damage associated molecular patterns (DAMPs), which trigger innate immune and inflammatory cascade via pattern recognition receptors. Neutrophils are recruited to the liver after I/R and contribute to the organ damage, innate immune and inflammatory responses. Formation of neutrophil extracellular trap (NET) has been recently found in response to various stimuli. However, the role of NETs during liver I/R injury remains unknown. We show that NETs form in the sinusoids of ischemic liver lobes in vivo. This was associated with increased NET markers, serum level of myeloperoxidase (MPO)-DNA complexes and tissue level of citrullinated-histone H3 compared to control mice. Treatment with peptidyl-arginine-deiminase (PAD) 4 inhibitor or DNase I significantly protected hepatocytes and reduced inflammation after liver I/R as evidenced by inhibition of NET formation, indicating the pathophysiological role of NETs in liver I/R injury. In vitro, NETs increase hepatocyte death and induce Kupffer cells to release proinflammatory cytokines. DAMPs, such as HMGB1 and histones, released by injured hepatocytes stimulate NET formation through Toll-like receptor (TLR4)- and TLR9-MyD88 signaling pathways. After neutrophil depletion in mice, the adoptive transfer of TLR4 knockout (KO) or TLR9 KO neutrophils confers significant protection from liver I/R injury with significant decrease in NET formation. In addition, we found inhibition of NET formation by PAD4 inhibitor or DNase I reduces HMGB1 and histone-mediated liver I/R injury. Conclusion DAMPs released during liver I/R promotes NET formation through TLRs signaling pathway. Development of NETs subsequently exacerbates organ damage and initiates inflammatory responses during liver I/R. PMID:25855125

  20. Treatment effects of Co-amoxiclav (Amoxiclav 2x in acute exacerbation of severe chronic obstructive pulmonary disease: Clinical evaluation

    Directory of Open Access Journals (Sweden)

    Andrijević Ilija

    2011-01-01

    Full Text Available Introduction. The exacerbation of chronic obstructive pulmonary disease is most often induced by an infection of bacterial origin in over 50% of the cases (or mixed bacterial and viral infection. This study was aimed at evaluating clinical effects of antibiotics co-amoxiclav. Amoxiicillin with clavulanic acid in the treatment of patients with severe chronic obstructive pulmonary disease exacerbation. Material and Methods. The investigation included 38 patients with severe chronic obstructive pulmonary disease exacerbation hospitalized at the Institute for Pulmonary Diseases of Vojvodina, Sremska Kamenica. The patients were randomly selected for the antibiotic treatment with Amoxiclav twice a day in 12 hour intervals. The clinical effects of the applied treatment were evaluated by analyzing certain laboratory findings, microbiological sputum findings and improvement of subjective symptoms. Results. Of the examined subjects, 65% were males and 35% were females, their mean age being 66.4+8.86, and who were mostly smokers (73%. After the completion of applied antibiotic treatment, a significant reduction and normalization of all inflammation markers were recorded, as well as a significant improvement of the patients’ subjective symptoms. The positive microbiological sputum findings (Haemophilus influenzae, Pseudomonas aeruginosa and Streptococcus pneumoniae were recorded in 13.58% of the patients. The bacterial agent was eradicated on the third day of the applied treatment. The mean length of the treatment was 7.07+0.91 days, with no undesirable treatment side effects observed. Conclusion. The antibiotic therapy is justifiable as the initial treatment regimen of severe chronic obstructive pulmonary disease exacerbation and amoxicillin with clavulanic acid is reported as the first-line antibiotic drug in most pharmacotherapy guidelines.

  1. Prediction and course of symptoms and lung function around an exacerbation in chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    van den Berge Maarten

    2012-06-01

    Full Text Available Abstract Background Frequent exacerbations induce a high burden to Chronic Obstructive Pulmonary Disease (COPD. We investigated the course of exacerbations in the published COSMIC study that investigated the effects of 1-year withdrawal of fluticasone after a 3-month run-in treatment period with salmeterol/fluticasone in patients with COPD. Methods In 373 patients, we evaluated diary cards for symptoms, Peak Expiratory Flow (PEF, and salbutamol use and assessed their course during exacerbations. Results There were 492 exacerbations in 224 patients. The level of symptoms of cough, sputum, dyspnea and nocturnal awakening steadily increased from 2 weeks prior to exacerbation, with a sharp rise during the last week. Symptoms of cough, sputum, and dyspnea reverted to baseline values at different rates (after 4, 4, and 7 weeks respectively, whereas symptoms of nocturnal awakening were still increased after eight weeks. The course of symptoms was similar around a first and second exacerbation. Increases in symptoms and salbutamol use and decreases in PEF were associated with a higher risk to develop an exacerbation, but with moderate predictive values, the areas under the receiver operating curves ranging from 0.63 to 0.70. Conclusions Exacerbations of COPD are associated with increased symptoms that persist for weeks and the course is very similar between a first and second exacerbation. COPD exacerbations are preceded by increased symptoms and salbutamol use and lower PEF, yet predictive values are too low to warrant daily use in clinical practice.

  2. The importance of bacterial and viral infections associated with adult asthma exacerbations in clinical practice.

    Directory of Open Access Journals (Sweden)

    Motoyasu Iikura

    Full Text Available Viral infection is one of the risk factors for asthma exacerbation. However, which pathogens are related to asthma exacerbation in adults remains unclear.The relation between various infections and adult asthma exacerbations was investigated in clinical practice.The study subjects included 50 adult inpatients due to asthma exacerbations and 20 stable outpatients for comparison. The pathogens from a nasopharyngeal swab were measured by multiplex PCR analysis.Asthma exacerbations occurred after a common cold in 48 inpatients. The numbers of patients with viral, bacterial, or both infections were 16, 9, and 9, respectively. The dominant viruses were rhinoviruses, respiratory syncytial virus, influenza virus, and metapneumovirus. The major bacteria were S. pneumoniae and H. influenzae. Compared to pathogen-free patients, the patients with pathogens were older and non-atopic and had later onset of disease, lower FeNO levels, lower IgE titers, and a higher incidence of comorbid sinusitis, COPD, or pneumonia. Compared to stable outpatients, asthma exacerbation inpatients had a higher incidence of smoking and comorbid sinusitis, COPD, or pneumonia. Viruses were detected in 50% of stable outpatients, but a higher incidence of rhinovirus, respiratory syncytial virus, and metapneumovirus infections was observed in asthma exacerbation inpatients. H. influenzae was observed in stable asthmatic patients. Other bacteria, especially S. pneumoniae, were important in asthma exacerbation inpatients.Viral or bacterial infections were observed in 70% of inpatients with an asthma exacerbation in clinical practice. Infection with S. pneumoniae was related to adult asthma exacerbation.

  3. Chronic Hepatitis B with Spontaneous Severe Acute Exacerbation

    Directory of Open Access Journals (Sweden)

    Wei-Lun Tsai

    2015-11-01

    Full Text Available Chronic hepatitis B virus (HBV infection is a major global health problem with an estimated 400 million HBV carriers worldwide. In the natural history of chronic hepatitis B (CHB, spontaneous acute exacerbation (AE is not uncommon, with a cumulative incidence of 10%–30% every year. While exacerbations can be mild, some patients may develop hepatic decompensation and even die. The underlying pathogenesis is possibly related to the activation of cytotoxic T lymphocyte-mediated immune response against HBV. An upsurge of serum HBV DNA usually precedes the rise of alanine aminotransferase (ALT and bilirubin. Whether antiviral treatment can benefit CHB with severe AE remains controversial, but early nucleos(tide analogues treatment seemed to be associated with an improved outcome. There has been no randomized study that compared the effects of different nucleos(tide analogues (NA in the setting of CHB with severe AE. However, potent NAs with good resistance profiles are recommended. In this review, we summarized current knowledge regarding the natural history, pathogenetic mechanisms, and therapeutic options of CHB with severe AE.

  4. Acute exacerbation of autoimmune hepatitis induced by Twinrix

    Institute of Scientific and Technical Information of China (English)

    Antal Csepregi; Gerhard Treiber; Christoph R(o)cken; Peter Malfertheiner

    2005-01-01

    We report on a 26-year-old man who presented with severe jaundice and elevated serum liver enzyme activities after having received a dose of Twinrix(○R). In his past medical history, jaundice or abnormal liver function tests were never recorded. Following admission, an elevated immunoglobulin G level and antinuclear antibodies at a titer of 320 with a homogenous pattern were found. Histology of a liver biopsy showed marked bridging liver fibrosis and a chronic inflammation, compatible with autoimmune hepatitis. Treatment was started with budesonide and ursodeoxycholic acid,and led to complete normalization of the pathological liver function tests. We believe that Twinrix(○R) led to an acute exacerbation of an unrecognized autoimmune hepatitis in our patient. The pathogenesis remains to be clarified. It is tempting to speculate that inactivated hepatitis A virus and/or recombinant surface antigen of the hepatitis B virus -as seen in patients with chronic hepatitis C and unrecognized autoimmune hepatitis who were treated with interferon alpha-might have been responsible for disease exacerbation.

  5. Relevance of human metapneumovirus in exacerbations of COPD

    Directory of Open Access Journals (Sweden)

    Bauer TT

    2005-12-01

    Full Text Available Abstract Background and methods Human metapneumovirus (hMPV is a recently discovered respiratory virus associated with bronchiolitis, pneumonia, croup and exacerbations of asthma. Since respiratory viruses are frequently detected in patients with acute exacerbations of COPD (AE-COPD it was our aim to investigate the frequency of hMPV detection in a prospective cohort of hospitalized patients with AE-COPD compared to patients with stable COPD and to smokers without by means of quantitative real-time RT-PCR. Results We analysed nasal lavage and induced sputum of 130 patients with AE-COPD, 65 patients with stable COPD and 34 smokers without COPD. HMPV was detected in 3/130 (2.3% AE-COPD patients with a mean of 6.5 × 105 viral copies/ml in nasal lavage and 1.88 × 105 viral copies/ml in induced sputum. It was not found in patients with stable COPD or smokers without COPD. Conclusion HMPV is only found in a very small number of patients with AE-COPD. However it should be considered as a further possible viral trigger of AE-COPD because asymptomatic carriage is unlikely.

  6. Taking into account of the aging and the damage in the size determination of composite materials structures; Prise en compte du vieillissement et de l'endommagement dans le dimensionnement de structures en materiaux composites

    Energy Technology Data Exchange (ETDEWEB)

    Mercier, J

    2006-11-15

    The aim of this study was to better understand the aging of glass fibres-epoxy composites exposed to humid conditions and loading so as to predict its effects on the lifetimes of composite structures. Water diffusion was first experimentally investigated by gravimetric method to determine water sorption kinetics for different humid conditions. A Fickian model of diffusion could describe the results obtained. Specimens, saturated at different levels, were mechanically characterised. Decreases of mechanical properties as a function of water uptake were revealed by tensile tests. Damage by cracking and the coupling with humidity were then studied. Differences between reversible and irreversible changes in properties were revealed and analysed in detail. A predictive model taking into account effects due to water and/or mechanical loading is proposed, using finite element method. As a first step, in modelling the diffusion process, the non-uniform water distribution across the composite are determined for any conditions (temperature, humidity, aging time). The resulting mechanical properties of the material, as a function of the absorbed water concentration, are determined in each point. Then, diffusion/mechanic coupled calculation allows to determine material global properties from properties at each point. It is then possible to predict continuous evolution of rigidity during aging time, at all stages of water absorption and matrix cracking, for any condition (temperature, humidity, thickness, mechanical loading level). (author)

  7. Ozone Damages to Mediterranean Crops: Physiological Responses

    Directory of Open Access Journals (Sweden)

    Massimo Fagnano

    2011-02-01

    Full Text Available In this brief review we analyzed some aspects of tropospheric ozone damages to crop plants. Specifically, we addressed this issue to Mediterranean environments, where plant response to multiple stresses may either exacerbate or counteract deleterious ozone effects. After discussing the adequacy of current models to predict ozone damages to Mediterranean crops, we present a few examples of physiological responses to drought and salinity stress that generally overlap with seasonal ozone peaks in Southern Italy. The co-existence of multiple stresses is then analyzed in terms of stomatal vs. non-stomatal control of ozone damages. Recent results on osmoprotectant feeding experiments, as a non-invasive strategy to uncouple stomatal vs. non stomatal contribution to ozone protection, are also presented. In the final section, we discuss critical needs in ozone research and the great potential of plant model systems to unravel multiple stress responses in agricultural crops.

  8. Economic measurement of environment damages

    Energy Technology Data Exchange (ETDEWEB)

    Krawiec, F.

    1980-05-01

    The densities, energy consumption, and economic development of the increasing population exacerbate environmental degradation. Air and water pollution is a major environmental problem affecting life and health, outdoor recreation, household soiling, vegetation, materials, and production. The literature review indicated that numerous studies have assessed the physical and monetary damage to populations at risk from excessive concentrations of major air and water pollutants-sulfur dioxide, total suspended particulate matter, oxidants, and carbon monoxide in air; and nutrients, oil, pesticides, and toxic metals and others in water. The measurement of the damages was one of the most controversial issues in pollution abatement. The methods that have been used to estimate the societal value of pollution abatement are: (1) chain of effects, (2) market approaches, and (3) surveys. National gross damages of air pollution of $20.2 billion and of water pollution of $11.1 billion for 1973 are substantial. These best estimates, updated for the economic and demographic conditions, could provide acceptable control totals for estimating and predicting benefits and costs of abating air and water pollution emissions. The major issues to be resolved are: (1) lack of available noneconomic data, (2) theoretical and empirical difficulties of placing a value on human life and health and on benefits such as aesthetics, and (3) lack of available demographic and economic data.

  9. Ageing management

    International Nuclear Information System (INIS)

    Ageing management is generally defined in a broad sense covering not only ageing management of hardware (structures, systems and components), but also management issues such as keeping up with developments in state-of-the-art technology and the latest management practices. The importance assigned to traditional ageing management, in terms of issues related to hardware degradation problems, is clearly very high. The other aspects, for example developments in engineering or management, are considered important as well, but are less emphasized. Plant ageing management is composed of the following necessary elements, which are all linked together: understanding and knowledge of ageing-related damage mechanisms, including benchmarking of the consequences of damage mechanisms into macroscopic behaviour of materials and structures under applicable conditions; predictive models to extrapolate behaviour of systems, structures or components up to a defined time; qualified methods for detection and surveillance of ageing degradation; qualified mitigation, repair and replacements measures; reliable plant documentation, including optimisation of the ageing management programme based on current understanding and knowledge and periodic self-assessment; availability of a technical service and knowledge base. The subject of plant ageing management has gained increasing attention over the past years, notably as more nuclear power plants across the world are being considered for lifetime extension. In this context, the NEA has conducted numerous technical studies to assess the impact of ageing mechanisms on safe and reliable plant operation. International research activities have also been initiated or are under way to provide the technical basis for decision making. This article provides an overview of some of the activities and accomplishments of the NEA Committee on the Safety of Nuclear Installations (CSNI) Working Group on the Integrity and Ageing of Components and Structures

  10. Purple Sweet Potato Color Ameliorates Cognition Deficits and Attenuates Oxidative Damage and Inflammation in Aging Mouse Brain Induced by D-Galactose

    Directory of Open Access Journals (Sweden)

    Qun Shan

    2009-01-01

    Full Text Available Purple sweet potato color (PSPC, a naturally occurring anthocyanin, has a powerful antioxidant activity in vitro and in vivo. This study explores whether PSPC has the neuroprotective effect on the aging mouse brain induced by D-galactose (D-gal. The mice administrated with PSPC (100 mg/kg.day, 4 weeks, from 9th week via oral gavage showed significantly improved behavior performance in the open field and passive avoidance test compared with D-gal-treated mice (500 mg/kg.day, 8 weeks. We further investigate the mechanism involved in neuroprotective effects of PSPC on mouse brain. Interestingly, we found, PSPC decreased the expression level of glial fibrillary acidic protein (GFAP, inducible nitric oxide synthase (iNOS, and cyclooxygenase-2 (COX-2, inhibited nuclear translocation of nuclear factor-kappaB (NF-κB, increased the activity of copper/zinc superoxide dismutase (Cu/Zn-SOD and catalase (CAT, and reduced the content of malondialdehyde (MDA, respectively. Our data suggested that PSPC attenuated D-gal-induced cognitive impairment partly via enhancing the antioxidant and anti-inflammatory capacity.

  11. Variability of antibiotic prescribing in patients with chronic obstructive pulmonary disease exacerbations: a cohort study

    OpenAIRE

    Boggon, R; Hubbard, R.; Smeeth, L; Gulliford, M; Cassell, J; Eaton, S; Pirmohamed, M; Van Staa, TP

    2013-01-01

    Background: The role of antibiotics in treating mild or moderate exacerbations in patients with acute chronic obstructive pulmonary disease (COPD) is unclear. The aims were to: (i) describe patient characteristics associated with acute exacerbations amongst a representative COPD population, (ii) explore the relationship between COPD severity and outcomes amongst patients with exacerbations, and (iii) quantify variability by general practice in prescribing of antibiotics for COPD exacerba...

  12. Embryo mortality in Isg15-/- mice is exacerbated by environmental stress.

    Science.gov (United States)

    Henkes, Luiz E; Pru, James K; Ashley, Ryan L; Anthony, Russell V; Veeramachaneni, D N Rao; Gates, Katherine C; Hansen, Thomas R

    2015-02-01

    The interferon-stimulated gene 15 (Isg15) encodes a ubiquitin-like protein that is induced in the endometrium by pregnancy in mice, humans, and ruminants. Because ISG15 is a component of the innate immune system, we hypothesized that development of the embryo, fetus, and postnatal pup may be impaired in mice lacking Isg15 (Isg15(-/-)) and that this development would be further impaired in response to environmental insults such as hypoxia. The number of implantation sites, resorption sites, dead embryos, and the changes in overall gross morphology of the uterus were evaluated in Isg15(-/-) mice on Days 7.5 and 12.5 postcoitum (dpc). Postnatal development also was monitored from birth to 12 wk of age. On 7.5 dpc, the number of implantation sites and serum progesterone concentrations were similar. However, embryo mortality increased (P pups; n = 47 litters). Embryo mortality in Isg15(-/-) mice was further exacerbated to 70% when dams were stressed through housing under hypoxic conditions (PB = 445 mmHg; 6.5-12.5 dpc). Transmission electron microscopy revealed lesions in antimesometrial decidua as well as trophoblast cells adjacent to decidual cells on 7.5 dpc. ISG15 was localized to mesometrial decidua on 7.5 dpc. By 12.5 dpc, ISG15 was intensely localized to the labyrinth of the placenta. By 7.5 dpc, uterine natural killer cell migration into the mesometrial pole was diminished by 65% and was less prevalent in Isg15(-/-) compared to Isg15(+/+) deciduum. Postnatal growth rate of offspring that survived to birth from Isg15(-/-) and Isg15(+/+) dams was not different. Embryo mortality occurs in pregnant Isg15(-/-) mice, is exacerbated by environmental insults like maternal hypoxia, and might result from impaired early decidualization, vascular development, and formation of the labyrinth. PMID:25505199

  13. Changes in p-wave amplitude and axis after treatment of chronic obstructive pulmonary disease exacerbation

    International Nuclear Information System (INIS)

    To compare the change in P-wave amplitude and axis before and after 24 hours of the treatment of chronic obstructive pulmonary disease exacerbation. Study Design: Quasi-experimental study. Place and Duration of Study: Department of medicine, PNS Shifa Karachi from Dec-2010 to June-2011 (six months). Material and Methods: A total of 93 subjects were included in the study. Their pre-treatment and post treatment ECGs were evaluated by measuring P-wave amplitudes in leads II and aVF and P-wave axes were calculated. The differences in terms of changes in P-wave amplitude and axis were compared. Results: Mean age of patients was 53.09 ± 7.20 years. Before treatment P-wave amplitude in lead II was 2.36 ± 0.34 mm and after treatment it was 1.73 ± 0.29 mm (p < 0.001). P-wave amplitude in lead aVF before treatment was 2.446 ± 0.334 mm while after treatment it was 1.556 ± 0.329 mm (p < 0.001). P-wave axis before treatment was 72.670 ± 4.670 and after 24 hours of treatment it was 63.750 ± 3.950 (p < 0.001). Conclusion: Significant changes in terms of reduction of P-wave amplitude and left ward rotation of P-wave axis occur after effective treatment of acute exacerbation of COPD. These findings provide valuable objective evidence in evaluating patient's response to treatment and recommended to be used in clinical practice. (author)

  14. FACTORS ASSOCIATED WITH QUALITY OF LIFE IN ACUTE EXACERBATION OF COPD

    Institute of Scientific and Technical Information of China (English)

    CAO Zhen-ying; Tan Wan Cheng; Ng Tze Pin

    2005-01-01

    Objective To measure the QOL in patients with AECOPD and the frequency of potential risk factors, and to evaluate the association of risk factors with poor QOL in patients with AECOPD. Methods A study sample of 196 patients with moderate to severe COPD admitted for acute exacerbations to two large general hospitals were studied. The St George QOL (SGQOL) scale, socio-demographic, clinical and patient care characteristics, including depression and spirometry were ascertained in the stable state before discharge and at one-month post discharge. Results There was a high prevalence of current or ex-heavy smokers, depression and consumption of psychotropic drugs, and low prevalence of care giver support, pulmonary rehabilitation and vaccination. The mean scores for the different domains were 55.9 for Symptoms; 65.1 for Activity; 32.9 for Impact; and the mean of overall Total scores was 46.5. Multiple regression analysis showed that CMH, male, depression, previous frequent hospital readmissions and poor therapy compliance were independently related to worse Symptoms Scores. Previous frequent readmissions, depression, severe dyspnea and older age (>72 years) were related to worse Activity Scores of SGQOL. Depression, previous frequent readmissions, severe dyspnea, long COPD duration(≥5years) and severe smoking were related to worse Impact Scores of SGQOL. Depression, previous frequent readmissions, severe dyspnea and long COPD duration(≥5years) were independently related to worse Total Scores of SGQOL.Conclusion Poor QOL in patients with COPD exacerbation was associated with disease severity, psychosocial and health care factors which are modifiable.

  15. Demographic Consequences of Defeating Aging

    OpenAIRE

    Gavrilov, Leonid A.; Gavrilova, Natalia S.

    2010-01-01

    A common objection against starting a large-scale biomedical war on aging is the fear of catastrophic population consequences (overpopulation). This fear is only exacerbated by the fact that no detailed demographic projections for radical life extension scenario have been conducted so far. This study explores different demographic scenarios and population projections, in order to clarify what could be the demographic consequences of a successful biomedical war on aging. A general conclusion o...

  16. Defining moderate asthma exacerbations in clinical trials based on ATS/ERS joint statement

    DEFF Research Database (Denmark)

    Virchow, J Christian; Backer, Vibeke; de Blay, Frédéric;

    2015-01-01

    BACKGROUND: Exacerbations are a key outcome in clinical research, providing patient-relevant information about symptomatic control, health state and disease progression. Generally considered as an episode of (sub)acute deterioration of respiratory symptoms, a precise, clinically useful definition...... al. (2009) [1] which provides a conceptual (or 'theoretical') definition for moderate exacerbations, to an operational (or 'practical') criterion suitable for use in clinical research. RESULTS: The proposed definition for a moderate exacerbation requires ≥1 of the following criteria combined with a...... exacerbations is needed. The proposed definition has been endorsed by the EMA Scientific Advice Working Party in 2011and needs to be trialled in forthcoming clinical studies....

  17. The Christmas Season as a Risk Factor for Chronic Obstructive Pulmonary Disease Exacerbations

    Directory of Open Access Journals (Sweden)

    Neil W Johnston

    2010-01-01

    Full Text Available BACKGROUND: Epidemics of hospitalization for chronic obstructive pulmonary disease (COPD occur annually during the Christmas holidays, and COPD exacerbations commonly coincide with respiratory viral infections.

  18. Monitoring asthma in childhood: symptoms, exacerbations and quality of life.

    Science.gov (United States)

    Brand, Paul L P; Mäkelä, Mika J; Szefler, Stanley J; Frischer, Thomas; Price, David

    2015-06-01

    Monitoring asthma in children in clinical practice is primarily performed by reviewing disease activity (daytime and night-time symptoms, use of reliever medication, exacerbations requiring frequent use of reliever medication and urgent visits to the healthcare professional) and the impact of the disease on children's daily activities, including sports and play, in a clinical interview. In such an interview, most task force members also discuss adherence to maintenance therapy and the patients' (and parents') views and beliefs on the goals of treatment and the amount of treatment required to achieve those goals. Composite asthma control and quality of life measures, although potentially useful in research, have limited value in clinical practice because they have a short recall window and do not cover the entire spectrum of asthma control. Telemonitoring of children with asthma cannot replace face-to-face follow-up and monitoring because there is no evidence that it is associated with improved health outcomes. PMID:26028631

  19. A rare case of ulcerative colitis exacerbated by VZV infection.

    Science.gov (United States)

    Nishimura, Satoshi; Yoshino, Takuya; Fujikawa, Yoshiki; Watanabe, Masaki; Yazumi, Shujiro

    2015-12-01

    A 16-years old man with severe ulcerative colitis (UC) was admitted to our hospital. After initiating treatment with corticosteroid for UC, chicken pox appeared. At the same time of appearance of chicken pox, the disease activity of UC was exacerbated. After initiating the treatment with acyclovir, both chicken pox and UC improved. Because colonoscopic findings revealed the remaining of moderately active UC, initiating the treatment with infliximab could induce clinical remission of UC without relapse of varicella-zoster virus (VZV) infection. This is a very rare case of UC with concomitant VZV infection. According to our report, the vaccination for VZV prior to immunosuppressive treatments would be necessary for VZV naïve patients with UC. PMID:26552918

  20. Fine particulate matter in acute exacerbation of COPD.

    Science.gov (United States)

    Ni, Lei; Chuang, Chia-Chen; Zuo, Li

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) is a common airway disorder. In particular, acute exacerbations of COPD (AECOPD) can significantly reduce pulmonary function. The majority of AECOPD episodes are attributed to infections, although environmental stress also plays a role. Increasing urbanization and associated air pollution, especially in developing countries, have been shown to contribute to COPD pathogenesis. Elevated levels of particulate matter (PM) in polluted air are strongly correlated with the onset and development of various respiratory diseases. In this review, we have conducted an extensive literature search of recent studies of the role of PM2.5 (fine PM) in AECOPD. PM2.5 leads to AECOPD via inflammation, oxidative stress (OS), immune dysfunction, and altered airway epithelial structure and microbiome. Reducing PM2.5 levels is a viable approach to lower AECOPD incidence, attenuate COPD progression and decrease the associated healthcare burden. PMID:26557095

  1. Fine particulate matter in acute exacerbation of COPD

    Directory of Open Access Journals (Sweden)

    Lei eNi

    2015-10-01

    Full Text Available Chronic obstructive pulmonary disease (COPD is a common airway disorder. In particular, acute exacerbations of COPD (AECOPD can significantly reduce pulmonary function. The majority of AECOPD episodes are attributed to infections, although environmental stress also plays a role. Increasing urbanization and associated air pollution, especially in developing countries, have been shown to contribute to COPD pathogenesis. Elevated levels of particulate matter (PM in polluted air are strongly correlated with the onset and development of various respiratory diseases. In this review, we have conducted an extensive literature search of recent studies of the role of PM2.5 (fine PM in AECOPD. PM2.5 leads to AECOPD via inflammation, oxidative stress, immune dysfunction, and altered airway epithelial structure and microbiome. Reducing PM2.5 levels is a viable approach to lower AECOPD incidence, attenuate COPD progression and decrease the associated healthcare burden.

  2. Will climate change exacerbate water stress in Central Asia?

    DEFF Research Database (Denmark)

    Siegfried, Tobias; Bernauer, Thomas; Guiennet, Renaud;

    2012-01-01

    Soviet Union collapsed. Will climate change exacerbate water stress and thus conflicts? We have developed a coupled climate, land-ice and rainfall-runoff model for the Syr Darya to quantify impacts and show that climatic changes are likely to have consequences on runoff seasonality due to earlier snow......Millions of people in the geopolitically important region of Central Asia depend on water from snow- and glacier-melt driven international rivers, most of all the Syr Darya and Amu Darya. The riparian countries of these rivers have experienced recurring water allocation conflicts ever since the......, and politically unstable Fergana Valley. Targeted infrastructural developments will be required in the region. If the current mismanagement of water and energy resources can be replaced with more effective resource allocation mechanisms through the strengthening of transboundary institutions, Central...

  3. [Etiological and exacerbation factors for COPD. Body weight loss].

    Science.gov (United States)

    Yokoyama, Akihito

    2016-05-01

    Hunger or malnutrition is not only a historical issue but also a current problem worldwide. Biological responses to hunger are evolutionary prepared in our body, including energy generation by degradation of body proteins. Extreme weight loss (malnutrition) can cause air space enlargement in human and rodents. However, the changes in rodents could be reversible, since refeeding could repair the pathology. On the other hand, weight loss is a common feature in patients with more severe COPD. Complex factors, such as increased energy consumption, decreased food uptake by low grade inflammation, socio-economic factors and so on, are involved in weight loss. Weight loss in patients with COPD also increases the risk of exacerbation, hospitalization, and death. PMID:27254941

  4. Damage database

    Czech Academy of Sciences Publication Activity Database

    Drdácký, Miloš; Valach, Jaroslav; Křemen, P.; Abrahamčík, J.

    Prague: Institute of theoretical and applied mechanics AS CR, v.v.i, 2011 - (Drdácký, M.; Binda, L.; Hennen, I.; Kőpp, C.; Lanza, L.), s. 185-195 ISBN 978-80-86246-37-6 Grant ostatní: evropská komise(XE) CHEF-SSPI-044251 Institutional research plan: CEZ:AV0Z20710524 Keywords : flood * damage * cultural heritage Subject RIV: AL - Art, Architecture, Cultural Heritage

  5. DNA damage

    OpenAIRE

    Kumari, Sunita; Rastogi, Rajesh P.; Singh, Kanchan L.; Singh, Shailendra P; Sinha, Rajeshwar P.

    2008-01-01

    Even under the best of circumstances, DNA is constantly subjected to chemical modifications. Several types of DNA damage such as SSB (single strand break), DSB (double strand break), CPDs (cyclobutane pyrimidine dimers), 6-4PPs (6-4 photoproducts) and their Dewar valence isomers have been identified that result from alkylating agents, hydrolytic deamination, free radicals and reactive oxygen species formed by various photochemical processes including UV radiation. There are a n...

  6. Inflammation and airway microbiota during cystic fibrosis pulmonary exacerbations.

    Directory of Open Access Journals (Sweden)

    Edith T Zemanick

    Full Text Available BACKGROUND: Pulmonary exacerbations (PEx, frequently associated with airway infection and inflammation, are the leading cause of morbidity in cystic fibrosis (CF. Molecular microbiologic approaches detect complex microbiota from CF airway samples taken during PEx. The relationship between airway microbiota, inflammation, and lung function during CF PEx is not well understood. OBJECTIVE: To determine the relationships between airway microbiota, inflammation, and lung function in CF subjects treated for PEx. METHODS: Expectorated sputum and blood were collected and lung function testing performed in CF subjects during early (0-3d. and late treatment (>7d. for PEx. Sputum was analyzed by culture, pyrosequencing of 16S rRNA amplicons, and quantitative PCR for total and specific bacteria. Sputum IL-8 and neutrophil elastase (NE; and circulating C-reactive protein (CRP were measured. RESULTS: Thirty-seven sputum samples were collected from 21 CF subjects. At early treatment, lower diversity was associated with high relative abundance (RA of Pseudomonas (r = -0.67, p<0.001, decreased FEV(1% predicted (r = 0.49, p = 0.03 and increased CRP (r = -0.58, p = 0.01. In contrast to Pseudomonas, obligate and facultative anaerobic genera were associated with less inflammation and higher FEV₁. With treatment, Pseudomonas RA and P. aeruginosa by qPCR decreased while anaerobic genera showed marked variability in response. Change in RA of Prevotella was associated with more variability in FEV₁ response to treatment than Pseudomonas or Staphylococcus. CONCLUSIONS: Anaerobes identified from sputum by sequencing are associated with less inflammation and higher lung function compared to Pseudomonas at early exacerbation. CF PEx treatment results in variable changes of anaerobic genera suggesting the need for larger studies particularly of patients without traditional CF pathogens.

  7. Macrophage activation in acute exacerbation of idiopathic pulmonary fibrosis.

    Directory of Open Access Journals (Sweden)

    Jonas Christian Schupp

    Full Text Available Acute exacerbation (AE of idiopathic pulmonary fibrosis (IPF is a common cause of disease acceleration in IPF and has a major impact on mortality. The role of macrophage activation in AE of IPF has never been addressed before.We evaluated BAL cell cytokine profiles and BAL differential cell counts in 71 IPF patients w/wo AE and in 20 healthy volunteers. Twelve patients suffered from AE at initial diagnosis while sixteen patients developed AE in the 24 months of follow-up. The levels of IL-1ra, CCL2, CCL17, CCL18, CCL22, TNF-α, IL-1β, CXCL1 and IL-8 spontaneously produced by BAL-cells were analysed by ELISA.In patients with AE, the percentage of BAL neutrophils was significantly increased compared to stable patients. We found an increase in the production rate of the pro-inflammatory cytokines CXCL1 and IL-8 combined with an increase in all tested M2 cytokines by BAL-cells. An increase in CCL18 levels and neutrophil counts during AE was observed in BAL cells from patients from whom serial lavages were obtained. Furthermore, high baseline levels of CCL18 production by BAL cells were significantly predictive for the development of future AE.BAL cell cytokine production levels at acute exacerbation show up-regulation of pro-inflammatory as well as anti-inflammatory/ M2 cytokines. Our data suggest that AE in IPF is not an incidental event but rather driven by cellular mechanisms including M2 macrophage activation.

  8. Exposure to particulate hexavalent chromium exacerbates allergic asthma pathology

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, Brent C. [Department of Microbiology, Immunology and Tropical Medicine, The George Washington University, Washington, DC 20037 (United States); Department of Pharmacology and Physiology, The George Washington University, Washington, DC 20037 (United States); Constant, Stephanie L. [Department of Microbiology, Immunology and Tropical Medicine, The George Washington University, Washington, DC 20037 (United States); Patierno, Steven R. [Department of Pharmacology and Physiology, The George Washington University, Washington, DC 20037 (United States); GW Cancer Institute, The George Washington University, Washington, DC 20037 (United States); Jurjus, Rosalyn A. [Department of Anatomy and Regenerative Biology, The George Washington University, Washington, DC 20037 (United States); Ceryak, Susan M., E-mail: phmsmc@gwumc.edu [Department of Pharmacology and Physiology, The George Washington University, Washington, DC 20037 (United States)

    2012-02-15

    Airborne hexavalent chromate, Cr(VI), has been identified by the Environmental Protection Agency as a possible health threat in urban areas, due to the carcinogenic potential of some of its forms. Particulate chromates are produced in many different industrial settings, with high levels of aerosolized forms historically documented. Along with an increased risk of lung cancer, a high incidence of allergic asthma has been reported in workers exposed to certain inhaled particulate Cr(VI) compounds. However, a direct causal association between Cr(VI) and allergic asthma has not been established. We recently showed that inhaled particulate Cr(VI) induces an innate neutrophilic inflammatory response in BALB/c mice. In the current studies we investigated how the inflammation induced by inhaled particulate Cr(VI) might alter the pathology of an allergic asthmatic response. We used a well-established mouse model of allergic asthma. Groups of ovalbumin protein (OVA)-primed mice were challenged either with OVA alone, or with a combination of OVA and particulate zinc chromate, and various parameters associated with asthmatic responses were measured. Co-exposure to particulate Cr(VI) and OVA mediated a mixed form of asthma in which both eosinophils and neutrophils are present in airways, tissue pathology is markedly exacerbated, and airway hyperresponsiveness is significantly increased. Taken together these findings suggest that inhalation of particulate forms of Cr(VI) may augment the severity of ongoing allergic asthma, as well as alter its phenotype. Such findings may have implications for asthmatics in settings in which airborne particulate Cr(VI) compounds are present at high levels. -- Highlights: ► Allergic asthma correlated with exposure to certain inhaled particulate chromates. ► Direct causal association between Cr(VI) and allergic asthma not established. ► Cr exacerbated pathology and airway hyperresponsiveness in an OVA-challenged mouse. ► Particulate Cr

  9. Exposure to particulate hexavalent chromium exacerbates allergic asthma pathology

    International Nuclear Information System (INIS)

    Airborne hexavalent chromate, Cr(VI), has been identified by the Environmental Protection Agency as a possible health threat in urban areas, due to the carcinogenic potential of some of its forms. Particulate chromates are produced in many different industrial settings, with high levels of aerosolized forms historically documented. Along with an increased risk of lung cancer, a high incidence of allergic asthma has been reported in workers exposed to certain inhaled particulate Cr(VI) compounds. However, a direct causal association between Cr(VI) and allergic asthma has not been established. We recently showed that inhaled particulate Cr(VI) induces an innate neutrophilic inflammatory response in BALB/c mice. In the current studies we investigated how the inflammation induced by inhaled particulate Cr(VI) might alter the pathology of an allergic asthmatic response. We used a well-established mouse model of allergic asthma. Groups of ovalbumin protein (OVA)-primed mice were challenged either with OVA alone, or with a combination of OVA and particulate zinc chromate, and various parameters associated with asthmatic responses were measured. Co-exposure to particulate Cr(VI) and OVA mediated a mixed form of asthma in which both eosinophils and neutrophils are present in airways, tissue pathology is markedly exacerbated, and airway hyperresponsiveness is significantly increased. Taken together these findings suggest that inhalation of particulate forms of Cr(VI) may augment the severity of ongoing allergic asthma, as well as alter its phenotype. Such findings may have implications for asthmatics in settings in which airborne particulate Cr(VI) compounds are present at high levels. -- Highlights: ► Allergic asthma correlated with exposure to certain inhaled particulate chromates. ► Direct causal association between Cr(VI) and allergic asthma not established. ► Cr exacerbated pathology and airway hyperresponsiveness in an OVA-challenged mouse. ► Particulate Cr

  10. Rehydration with soft drink-like beverages exacerbates dehydration and worsens dehydration-associated renal injury.

    Science.gov (United States)

    García-Arroyo, Fernando E; Cristóbal, Magdalena; Arellano-Buendía, Abraham S; Osorio, Horacio; Tapia, Edilia; Soto, Virgilia; Madero, Magdalena; Lanaspa, Miguel A; Roncal-Jiménez, Carlos; Bankir, Lise; Johnson, Richard J; Sánchez-Lozada, Laura-Gabriela

    2016-07-01

    Recurrent dehydration, such as commonly occurs with manual labor in tropical environments, has been recently shown to result in chronic kidney injury, likely through the effects of hyperosmolarity to activate both vasopressin and aldose reductase-fructokinase pathways. The observation that the latter pathway can be directly engaged by simple sugars (glucose and fructose) leads to the hypothesis that soft drinks (which contain these sugars) might worsen rather than benefit dehydration associated kidney disease. Recurrent dehydration was induced in rats by exposure to heat (36°C) for 1 h/24 h followed by access for 2 h to plain water (W), a 11% fructose-glucose solution (FG, same composition as typical soft drinks), or water sweetened with noncaloric stevia (ST). After 4 wk plasma and urine samples were collected, and kidneys were examined for oxidative stress, inflammation, and injury. Recurrent heat-induced dehydration with ad libitum water repletion resulted in plasma and urinary hyperosmolarity with stimulation of the vasopressin (copeptin) levels and resulted in mild tubular injury and renal oxidative stress. Rehydration with 11% FG solution, despite larger total fluid intake, resulted in greater dehydration (higher osmolarity and copeptin levels) and worse renal injury, with activation of aldose reductase and fructokinase, whereas rehydration with stevia water had opposite effects. In animals that are dehydrated, rehydration acutely with soft drinks worsens dehydration and exacerbates dehydration associated renal damage. These studies emphasize the danger of drinking soft drink-like beverages as an attempt to rehydrate following dehydration. PMID:27053647

  11. Efficacy of amoxycillin versus amoxycillin/clavulanate in acute exacerbations of chronic pulmonary obstructive disease in primary care

    Directory of Open Access Journals (Sweden)

    Carl Llor

    2008-10-01

    Full Text Available Carl Llor1, Silvia Hernández1, Anna Ribas2, Carmen Álvarez3, Josep Maria Cots4, Carolina Bayona5, Isabel González6, Marc Miravitlles7, BRAMOX Study Group 1Primary Care Centre Jaume I, Tarragona, Spain; 2Primary Care Centre Santa Eugènia de Berga, Spain; 3Primary Care Centre Manlleu, Spain; 4Primary Care Centre La Marina, Barcelona, Spain; 5Primary Care Centre Valls, Spain; 6Primary Care Centre Maragall, Barcelona, Spain; 7Pneumology Department. Institut Clínic del Tòrax (IDIBAPS, Hospital Clínic, Barcelona, CIBER de Enfermedades Respiratorias (CIBERES, SpainBackground: Amoxycillin/clavulanate is considered first-line treatment for ambulatory exacerbations of COPD. However, narrow-spectrum antibiotics may be as useful for mild to moderate patients.Objective: To compare the clinical efficacy of amoxycillin versus amoxicyllin/clavulanate in exacerbations of COPD in primary care.Methods: A randomized, double-blind, noninferiority clinical trial was carried out in eight primary care centers in Catalonia, Spain. Spirometrically-diagnosed patients older than 40 years with COPD, without criteria of hospitalization and Anthonisen’s types I or II exacerbations were included. The main outcome was clinical cure at the end of treatment (EOT visit on day 10.Results: A total of 137 patients were enrolled in the study (68 assigned to amoxycillin and 69 to amoxycillin/clavulanate. The mean forced expiratory flow in one second was 61.6% and the mean age was 71.4 years. At EOT, 92.8% of patients in the amoxycillin/clavulanate and 90.9% in the amoxycillin group were considered clinically cured, a statistically non-significant difference. Adverse effects were observed in 11 subjects, 3 in the amoxycillin group and 8 in the amoxycillin/clavulanate group, 2 of whom required a change in treatment.Conclusions: Amoxycillin was at least as effective clinically and as safe as amoxycilin/clavulanate in the treatment of acute exacerbations of COPD in mild to

  12. Impact of individualized care on readmissions after a hospitalization for acute exacerbation of COPD

    Directory of Open Access Journals (Sweden)

    Adamson SL

    2016-01-01

    Full Text Available Simon L Adamson,1 Jane Burns,1,2 Pat G Camp,1,2 Don D Sin,1,3 Stephan F van Eeden1,31The Centre for Heart Lung Innovation, St Paul’s Hospital, University of British Columbia, 2Department of Physical Therapy, 3Division of Respirology, Department of Medicine, University of British Columbia, Vancouver, BC, CanadaBackground: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD increase COPD morbidity and mortality and impose a great burden on health care systems. Early readmission following a hospitalization for AECOPD remains an important clinical problem. We examined how individualized comprehensive care influences readmissions following an index hospital admission for AECOPD.Methods: We retrospectively reviewed data of patients admitted for AECOPD to two inner-city teaching hospitals to determine the impact of a comprehensive and individualized care management strategy on readmissions for AECOPD. The control group consisted of 271 patients whose index AECOPD occurred the year before the comprehensive program, and the experimental group consisted of 191 patients who received the comprehensive care. The primary outcome measure was the total number of readmissions in 30- and 90-day postindex hospitalizations. Secondary outcome measures included the length of time between the index admission and first readmission and all-cause mortality.Results: The two groups were similar in terms of age, sex, forced expiratory volume in 1 second, body mass index (BMI, pack-years, and the number and types of comorbidities. Comprehensive care significantly reduced 90-day readmission rates in females (P=0.0205, corrected for age, BMI, number of comorbidities, substance abuse, and mental illness but not in males or in the whole group (P>0.05. The average times between index admission and first readmission were not different between the two groups. Post hoc multivariate analysis showed that substance abuse (P<0.01 increased 30- and 90-day

  13. 中老年人群血尿酸水平和早期肾功能损害的关系%Association between serum uric acid and early kidney damage in middle-aged and elderly

    Institute of Scientific and Technical Information of China (English)

    何森; 黄德嘉; 陈晓平; 蒋凌云; 彭勇; 龚玲; 陈小妮; 吴凯; 崔凯军; 祝烨

    2010-01-01

    Objective To investigate the association between serum uric acid (UA) and early kidney damage and the prevalence of early kidney damage [89≥GFR≥60 ml·min~(-1)·(1.73m~2)~(-1)]in the middle-aged and elders with normal serum creatinine.Methods A survey of cardiovascular risk factors,including serum UA and estimated glomerular filtration rate(eGFR) [according to MDRD (modification of diet in renal disease) equation ],was carried out in a local general population of Chendu. A total of 1023 subjects with normal serum creatinine [mean age:(63±6)years;male:female=52.7%:47.3%] were recruited by random sampling method.The subjects were divided into 4 groups (A,B,C,D)according to the quartiles of serum UA levels(A:UAwomen:19.5%,P<0.01).In men and women,serum UA and mild kidney dysfunction were negatively correlated,and the prevalence of early kidney damage significantly increased with the elevated level of serum UA. The prevalence of early kidney damage was higher in men than women(P<0.01).According to the logistic regression analysis adjusting for age,gender,waist,body mass index,triglyceride,HDL-C,total cholesterol,history of hypertension and diabetes type 2,the odds ratio of the prevalence of early kidney damage were 1.0[B:1.740(P=0.151),C:3.599(P=0.01)and D:5.488(P<0.01)respectively].Conclusion In the middle-aged and elders with normal serum creatinine,serum UA and eGFR are negatively correlated.And serum UA level is independently associated with early kidney damage.%目的 研究血肌酐正常的中老年人群血尿酸(UA)水平和早期肾功能损害的关系及其早期肾功能损害的患病率.方法 对成都的社区自然人群按照随机抽样方法抽取样本,对血肌酐正常的1023人,平均年龄(63±6)岁;进行了相关心血管危险因素的调查,其中包括血肌酐和血UA水平.评价肾功能采用MDRD方程估算的肾小球滤过率(eGFR).根据资料分析该人群早期肾功能损害[89≥eGFR≥60 ml·min~(-1)·(1.73 m~2

  14. Long-acting muscarinic antagonists for the prevention of exacerbations of chronic obstructive pulmonary disease.

    Science.gov (United States)

    Jones, Paul W

    2015-06-01

    Exacerbations of chronic obstructive pulmonary disease (COPD) have important consequences for lung function, health status and mortality. Furthermore, they are associated with high economic costs, predominantly related to hospitalization. They are managed acutely with short-acting bronchodilators, systemic corticosteroids or antibiotics; however, a large proportion of COPD exacerbations are unreported and therefore untreated or self-managed. There is evidence to suggest that these unreported exacerbations also have important consequences for health status; therefore, reducing exacerbation risk is an important goal in the management of COPD. Current guidelines recommend long-acting muscarinic antagonists (LAMAs) as first-line bronchodilator therapy in patients with stable COPD who have a high risk of exacerbation or increased symptoms. To date, three LAMAs, tiotropium bromide, aclidinium bromide and glycopyrronium bromide, have been approved as maintenance bronchodilator treatments for stable COPD. These all provide clinically significant improvements in lung function, reduce symptoms and improve health status compared with placebo in patients with COPD. This paper reviews evidence from randomized, controlled clinical trials demonstrating that tiotropium, aclidinium and glycopyrronium reduce exacerbation risk in patients with COPD. Reductions were seen irrespective of the exacerbation measure used, whether time to first event or annualized exacerbation rate. Furthermore, studies with aclidinium suggest LAMAs can reduce exacerbation risk irrespective of whether exacerbation events are assessed, using an event-based approach or a symptom-based method which includes unreported events. Together these results demonstrate that LAMAs have the potential to provide clinical benefit in the management of exacerbations in patients with stable COPD. PMID:25801643

  15. Exercise Promotes Healthy Aging of Skeletal Muscle.

    Science.gov (United States)

    Cartee, Gregory D; Hepple, Russell T; Bamman, Marcas M; Zierath, Juleen R

    2016-06-14

    Primary aging is the progressive and inevitable process of bodily deterioration during adulthood. In skeletal muscle, primary aging causes defective mitochondrial energetics and reduced muscle mass. Secondary aging refers to additional deleterious structural and functional age-related changes caused by diseases and lifestyle factors. Secondary aging can exacerbate deficits in mitochondrial function and muscle mass, concomitant with the development of skeletal muscle insulin resistance. Exercise opposes deleterious effects of secondary aging by preventing the decline in mitochondrial respiration, mitigating aging-related loss of muscle mass and enhancing insulin sensitivity. This review focuses on mechanisms by which exercise promotes "healthy aging" by inducing modifications in skeletal muscle. PMID:27304505

  16. Predictors of treatment with antibiotics and systemic corticosteroids for acute exacerbations of asthma and chronic obstructive pulmonary disease in primary care

    OpenAIRE

    Al-ani, Salwan Tariq; Spigt, Marcus; Laue, Johanna; Melbye, Hasse

    2015-01-01

    Background: Antibiotic and oral corticosteroid prescribing rate in patients suffering from acute exacerbations of chronic obstructive pulmonary disease (COPD) or asthma in general practice are only sparsely described. Our aim was to identify predictors for such prescribing when results from CRP testing, spirometry, and pulse oximetry are available. Methods: Patients aged 40 years or more diagnosed with asthma, COPD or both, the previous five years from seven general practice offices in Norway...

  17. High body mass index and risk of exacerbations and pneumonias in individuals with chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Çolak, Yunus; Afzal, Shoaib; Lange, Peter;

    2016-01-01

    descent, aged 20-100 years, from the Copenhagen General Population Study, for FTO (rs9939609), MC4R (rs17782313) and TMEM18 (rs6548238), and created an allele score. A total of 10 883 individuals had spirometric COPD with forced expiratory volume in 1 s (FEV1) / forced vital capacity (FVC) < lower limit......BACKGROUND: In the clinic, the combination of obesity and chronic obstructive pulmonary disease (COPD) has been increasing. However, whether high body mass index (BMI) affects the risk of exacerbations and pneumonias in individuals with COPD is presently unknown. Genetics can be used to assess the...... of normal (LLN). In these individuals, we observed 1453 exacerbations and 3390 pneumonias during 4.7 years of follow-up. RESULTS: For each increase in allele score, BMI was 0.28 kg/m(2) [95% confidence interval (CI): 0.25-0.30) higher. Age- and sex-adjusted genetic hazard ratios (HRs) per one allele...

  18. Altered gene expression in blood and sputum in COPD frequent exacerbators in the ECLIPSE cohort.

    Directory of Open Access Journals (Sweden)

    Dave Singh

    Full Text Available Patients with chronic obstructive pulmonary disease (COPD who are defined as frequent exacerbators suffer with 2 or more exacerbations every year. The molecular mechanisms responsible for this phenotype are poorly understood. We investigated gene expression profile patterns associated with frequent exacerbations in sputum and blood cells in a well-characterised cohort. Samples from subjects from the ECLIPSE COPD cohort were used; sputum and blood samples from 138 subjects were used for microarray gene expression analysis, while blood samples from 438 subjects were used for polymerase chain reaction (PCR testing. Using microarray, 150 genes were differentially expressed in blood (>±1.5 fold change, p≤0.01 between frequent compared to non-exacerbators. In sputum cells, only 6 genes were differentially expressed. The differentially regulated genes in blood included downregulation of those involved in lymphocyte signalling and upregulation of pro-apoptotic signalling genes. Multivariate analysis of the microarray data followed by confirmatory PCR analysis identified 3 genes that predicted frequent exacerbations; B3GNT, LAF4 and ARHGEF10. The sensitivity and specificity of these 3 genes to predict the frequent exacerbator phenotype was 88% and 33% respectively. There are alterations in systemic immune function associated with frequent exacerbations; down-regulation of lymphocyte function and a shift towards pro-apoptosis mechanisms are apparent in patients with frequent exacerbations.

  19. Mechanisms and impact of the frequent exacerbator phenotype in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Wedzicha, Jadwiga A; Brill, Simon E; Allinson, James P; Donaldson, Gavin C

    2013-01-01

    Exacerbations of chronic obstructive pulmonary disease (COPD) are important events that carry significant consequences for patients. Some patients experience frequent exacerbations, and are now recognized as a distinct clinical subgroup, the 'frequent exacerbator' phenotype. This is relatively stable over time, occurs across disease severity, and is associated with poorer health outcomes. These patients are therefore a priority for research and treatment. The pathophysiology underlying the frequent exacerbator phenotype is complex, with increased airway and systemic inflammation, dynamic lung hyperinflation, changes in lower airway bacterial colonization and a possible increased susceptibility to viral infection. Frequent exacerbators are also at increased risk from comorbid extrapulmonary diseases including cardiovascular disease, gastroesophageal reflux, depression, osteoporosis and cognitive impairment. Overall these patients have poorer health status, accelerated forced expiratory volume over 1 s (FEV1) decline, worsened quality of life, and increased hospital admissions and mortality, contributing to increased exacerbation susceptibility and perpetuation of the frequent exacerbator phenotype. This review article sets out the definition and importance of the frequent exacerbator phenotype, with a detailed examination of its pathophysiology, impact and interaction with other comorbidities. PMID:23945277

  20. 77 FR 59929 - Guidance for Industry on Acute Bacterial Exacerbations of Chronic Bronchitis in Patients With...

    Science.gov (United States)

    2012-10-01

    ... August 22, 2008 (73 FR 49684), which in turn revised the draft guidance for industry entitled ``Acute... ``Acute Bacterial Exacerbations of Chronic Bronchitis in Patients With Chronic Obstructive Pulmonary... treatment of acute bacterial exacerbations of chronic bronchitis in patients with chronic...

  1. Low-intensity noninvasive ventilation: Lower pressure, more exacerbations of chronic respiratory failure

    Directory of Open Access Journals (Sweden)

    Toru Kadowaki

    2016-01-01

    Conclusions: Attention should be paid to CRF patients who are initially administered LI-NPPV; they should be carefully observed because they can develop more exacerbations of CRF than patients undergoing C-NPPV. If possible, higher initial PS should be administered to prevent CRF exacerbations.

  2. A trial of beclomethasone/formoterol in COPD using EXACT-PRO to measure exacerbations

    DEFF Research Database (Denmark)

    Singh, Dave; Kampschulte, Jorg; Wedzicha, Jadwiga A;

    2013-01-01

    comparison of extrafine beclomethasone dipropionate and formoterol in a combination inhaler with extrafine formoterol; the co-primary end-points are exacerbation rates over 48 weeks and improvement in forced expiratory volume in 1 s over 12 weeks. The traditional physician diagnosis of exacerbations is a co...

  3. The role of viral infections in exacerbations of chronic obstructive pulmonary disease and asthma.

    Science.gov (United States)

    Hewitt, Richard; Farne, Hugo; Ritchie, Andrew; Luke, Emma; Johnston, Sebastian L; Mallia, Patrick

    2016-04-01

    Asthma and chronic obstructive pulmonary disease (COPD) are major causes of global morbidity and mortality worldwide. The clinical course of both asthma and COPD are punctuated by the occurrence of exacerbations, acute events characterized by increased symptoms and airflow obstruction. Exacerbations contribute most of the morbidity, mortality and excess healthcare costs associated with both asthma and COPD. COPD and asthma exacerbations are frequently associated with respiratory virus infections and this has led to an intense research focus into the mechanisms of virus-induced exacerbations over the past decade. Current therapies are effective in reducing chronic symptoms but are less effective in preventing exacerbations, particularly in COPD. Understanding the mechanisms of virus-induced exacerbation will lead to the development of new targeted therapies that can reduce the burden of virus-induced exacerbations. In this review we discuss current knowledge of virus-induced exacerbations of asthma and COPD with a particular focus on mechanisms, human studies, virus-bacteria interactions and therapeutic advances. PMID:26611907

  4. Modern biological theories of aging

    International Nuclear Information System (INIS)

    These proceedings contain 30 papers grouped under the headings of: Theories of aging: A perspective; Evolution of life span in placental mammals; Developmentally programmed aging; Free-radical damage; Error catastrophe; DNA Damage and repair; and Organ systems as pacemakers of aging

  5. Current asthma control predicts future risk of asthma exacerbation: a 12-month prospective cohort study

    Institute of Scientific and Technical Information of China (English)

    WEI Hua-hua; ZHOU Ting; WANG Lan; ZHANG Hong-ping; FU Juan-juan; WANG Lei; JI Yu-lin; WANG Gang

    2012-01-01

    Background The performance of asthma control test (ACT) at baseline for predicting future risk of asthma exacerbation has not been previously demonstrated.This study was designed to explore the ability of the baseline ACT score to predict future risk of asthma exacerbation during a 12-month follow-up.Methods This post hoc analysis included data from a 12-month prospective cohort study in patients with asthma (n=290).The time to the first asthma exacerbation was analyzed and the association between baseline ACT scores and future risk of asthma exacerbation was calculated as adjusted odds ratio (OR) using Logistic regression models.Further,sensitivity and specificity were estimated at each cut-point of ACT scores for predicting asthma exacerbations.Results The subjects were divided into three groups,which were uncontrolled (U,n=128),partly-controlled (PC,n=111),and well controlled (C,n=51) asthma.After adjustment,the decreased ACT scores at baseline in the U and PC groups were associated with an increased probability of asthma exacerbations (OR 3.65 and OR 5.75,respectively),unplanned visits (OR 8.03 and OR 8.21,respectively) and emergency visits (OR 20.00 and OR 22.60,respectively) over a 12-month follow-up period.The time to the first asthma exacerbation was shorter in the groups with U and PC asthma (all P<0.05).The baseline ACT of 20 identified as the cut-point for screening the patients at high risk of asthma exacerbations had an increased sensitivity of over 90.0% but a lower specificity of about 30.0%.Conclusion Our findings indicate that the baseline ACT score with a high sensitivity could rule out patients at low risk of asthma exacerbations and oredict future risk of asthma exacerbations in clinical practice.

  6. What Causes Our Skin to Age?

    Science.gov (United States)

    ... care Younger skin Causes of aging skin Creating anti-aging plan Fillers giving patients better, longer-lasting results Maximizing anti-aging products Selecting anti-aging products Sun damage Wrinkle ...

  7. Deficiency of Senescence Marker Protein 30 Exacerbates Cardiac Injury after Ischemia/Reperfusion

    OpenAIRE

    Shinpei Kadowaki; Tetsuro Shishido; Toshiki Sasaki; Takayuki Sugai; Taro Narumi; Yuki Honda; Yoichiro Otaki; Daisuke Kinoshita; Tetsuya Takahashi; Satoshi Nishiyama; Hiroki Takahashi; Takanori Arimoto; Takuya Miyamoto; Tetsu Watanabe; Akihiko Ishigami

    2016-01-01

    Early myocardial reperfusion is an effective therapy but ischemia/reperfusion (I/R) causes lethal myocardial injury. The aging heart was reported to show greater cardiac damage after I/R injury than that observed in young hearts. Senescence marker protein 30 (SMP30), whose expression decreases with age, plays a role in reducing oxidative stress and apoptosis. However, the impact of SMP30 on myocardial I/R injury remains to be determined. In this study, the left anterior descending coronary ar...

  8. Irradiation damage

    International Nuclear Information System (INIS)

    There is considerable interest in irradiation effects in intermetallic compounds from both the applied and fundamental aspects. Initially, this interest was associated mainly with nuclear reactor programs but it now extends to the fields of ion-beam modification of metals, behaviour of amorphous materials, ion-beam processing of electronic materials, and ion-beam simulations of various kinds. The field of irradiation damage in intermetallic compounds is rapidly expanding, and no attempt will be made in this chapter to cover all of the various aspects. Instead, attention will be focused on some specific areas and, hopefully, through these, some insight will be given into the physical processes involved, the present state of our knowledge, and the challenge of obtaining more comprehensive understanding in the future. The specific areas that will be covered are: point defects in intermetallic compounds; irradiation-enhanced ordering and irradiation-induced disordering of ordered alloys; irradiation-induced amorphization

  9. Irradiation damage

    Energy Technology Data Exchange (ETDEWEB)

    Howe, L.M

    2000-07-01

    There is considerable interest in irradiation effects in intermetallic compounds from both the applied and fundamental aspects. Initially, this interest was associated mainly with nuclear reactor programs but it now extends to the fields of ion-beam modification of metals, behaviour of amorphous materials, ion-beam processing of electronic materials, and ion-beam simulations of various kinds. The field of irradiation damage in intermetallic compounds is rapidly expanding, and no attempt will be made in this chapter to cover all of the various aspects. Instead, attention will be focused on some specific areas and, hopefully, through these, some insight will be given into the physical processes involved, the present state of our knowledge, and the challenge of obtaining more comprehensive understanding in the future. The specific areas that will be covered are: point defects in intermetallic compounds; irradiation-enhanced ordering and irradiation-induced disordering of ordered alloys; irradiation-induced amorphization.

  10. Genetic Mechanisms in Aspirin-Exacerbated Respiratory Disease

    Directory of Open Access Journals (Sweden)

    Nami Shrestha Palikhe

    2012-01-01

    Full Text Available Aspirin-exacerbated respiratory disease (AERD refers to the development of bronchoconstriction in asthmatics following the exposure to aspirin or other nonsteroidal anti-inflammatory drugs. The key pathogenic mechanisms associated with AERD are the overproduction of cysteinyl leukotrienes (CysLTs and increased CysLTR1 expression in the airway mucosa and decreased lipoxin and PGE2 synthesis. Genetic studies have suggested a role for variability of genes in disease susceptibility and the response to medication. Potential genetic biomarkers contributing to the AERD phenotype include HLA-DPB1, LTC4S, ALOX5, CYSLT, PGE2, TBXA2R, TBX21, MS4A2, IL10, ACE, IL13, KIF3A, SLC22A2, CEP68, PTGER, and CRTH2 and a four-locus SNP set composed of B2ADR, CCR3, CysLTR1, and FCER1B. Future areas of investigation need to focus on comprehensive approaches to identifying biomarkers for early diagnosis.

  11. Infection with Porphyromonas gingivalis exacerbates endothelial injury in obese mice.

    Directory of Open Access Journals (Sweden)

    Min Ao

    Full Text Available BACKGROUND: A number of studies have revealed a link between chronic periodontitis and cardiovascular disease in obese patients. However, there is little information about the influence of periodontitis-associated bacteria, Porphyromonas gingivalis (Pg, on pathogenesis of atherosclerosis in obesity. METHODS: In vivo experiment: C57BL/6J mice were fed with a high-fat diet (HFD or normal chow diet (CD, as a control. Pg was infected from the pulp chamber. At 6 weeks post-infection, histological and immunohistochemical analysis of aortal tissues was performed. In vitro experiment: hTERT-immortalized human umbilical vein endothelial cells (HuhT1 were used to assess the effect of Pg/Pg-LPS on free fatty acid (FFA induced endothelial cells apoptosis and regulation of cytokine gene expression. RESULTS: Weaker staining of CD31 and increased numbers of TUNEL positive cells in aortal tissue of HFD mice indicated endothelial injury. Pg infection exacerbated the endothelial injury. Immunohistochemically, Pg was detected deep in the smooth muscle of the aorta, and the number of Pg cells in the aortal wall was higher in HFD mice than in CD mice. Moreover, in vitro, FFA treatment induced apoptosis in HuhT1 cells and exposure to Pg-LPS increased this effect. In addition, Pg and Pg-LPS both attenuated cytokine production in HuhT1 cells stimulated by palmitate. CONCLUSIONS: Dental infection of Pg may contribute to pathogenesis of atherosclerosis by accelerating FFA-induced endothelial injury.

  12. Food-induced (allergic) arthritis. Inflammatory arthritis exacerbated by milk.

    Science.gov (United States)

    Panush, R S; Stroud, R M; Webster, E M

    1986-02-01

    Suggestive, but largely unproven, observations have associated arthritis with environmental antigens, including foods. We studied a patient with inflammatory arthritis in a prospective, "blinded," controlled fashion to determine whether her symptoms were associated with food sensitivities. This 52-year-old white woman with 11 years of class I, stage I, active disease, had symptomatic exacerbations allegedly associated with meat, milk, and beans. We observed an increase in symptoms following an unblinded food challenge and then studied her in our clinical research unit. On her normal diet for 6 days, she averaged 30 minutes of morning stiffness, 9 tender joints, 3 swollen joints, 87% subjective assessment (100% = best possible), and 89% examiner assessment. While she was fasting (3 days) or taking Vivonex (2 days), we noted no morning stiffness, tender joint score of 1, swollen joint score of 0, and assessments of 100% (P less than 0.05 versus normal diet). She was then nourished with Vivonex for 33 days without difficulty and challenged in a blinded fashion at mealtimes with lyophilized foods placed into opaque capsules. Four milk challenges (equivalent to greater than or equal to 8 ounces per meal) produced up to 30 minutes of morning stiffness, 14 tender joints, 4 swollen joints, subjective assessment of 85%, and objective assessment of 80% (P less than 0.05 versus fasting-Vivonex), peaking 24-48 hours postchallenge. Placebo and other foods (lettuce and carrots) were without effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3513771

  13. Influence of Pseudomonas aeruginosa on exacerbation in patients with bronchiectasis

    Directory of Open Access Journals (Sweden)

    Kiran Chawla

    2015-01-01

    Full Text Available Background: A majority of the studies done on the western population have shown that Pseudomonas aeruginosa causes many severe infections in patients with bronchiectasis as compared to other pathogens. There is scarcity of similar data from the Asian population. Materials and Methods: A prospective study was undertaken to identify the various pathogens isolated from the respiratory samples of 117 patients with bronchiectasis from south India and to compare the clinicomicrobiological profile of infections caused by P. aeruginosa and other respiratory pathogens. Results: The respiratory pathogens were isolated from 63 (53.8% patients. P. aeruginosa was the most common isolate (46.0% followed by Klebsiella pneumoniae (14.3% and other pathogenic bacteria. Patients included in the P. aeruginosa group had a higher number of exacerbations (p: 0.008, greater number of hospital admissions (p: 0.007, a prolonged hospital stay (p: 0.03, and poor lung function, compared to the patients infected with the non-Pseudomonas group. Conclusion: It is necessary to investigate the etiology of respiratory tract infections among bronchiectasis patients followed by the prompt management of cases diagnosed with P. aeruginosa infections, so as to lower the morbidity and have a better prognosis.

  14. Preventing and managing exacerbations in COPD – critical appraisal of the role of tiotropium

    Directory of Open Access Journals (Sweden)

    Donald P Tashkin

    2010-02-01

    Full Text Available Donald P TashkinDepartment of Medicine, Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine at UCLA,Los Angeles, CA, USAAbstract: The course of COPD is punctuated by acute exacerbations that are associated with an increase in the morbidity and mortality related to this chronic disease and may contribute to its rate of progression. Therefore, preventing and treating exacerbations are major goals of COPD management. The role of tiotropium in the prevention of exacerbations has been investigated in several placebo-controlled randomized clinical trials varying in duration from 3 months to 4 years in patients with moderate to very severe COPD. In all of these trials, tiotropium has uniformly reduced the proportion of patients experiencing at least one exacerbation and delayed the time to the first exacerbation compared with placebo. In the longer trials (≥6 months’ duration tiotropium has also reduced the exposure-adjusted incidence rate of exacerbations. In trials of at least 1 year in duration, tiotropium either significantly reduced the risk of hospitalization for an exacerbation and/or the proportion of patients with an exacerbation-related hospitalization. In a meta-analysis that included 15 trials of tiotropium vs either placebo (n = 13 and/or a longacting beta-agonist (LABA; n = 4, tiotropium significantly reduced the odds of experiencing an exacerbation compared to placebo as well as a LABA. The potential additive benefits of tiotropium to those of a LABA and/or inhaled corticosteroid in reducing exacerbations require further investigation. The mechanism whereby tiotropium reduces exacerbations is not due to an anti-inflammatory effect but more likely relates to its property of causing a sustained increase in airway patency and reduction in hyperinflation, thereby counteracting the tendency for respiratory insults to worsen airflow obstruction and hyperinflation. For the management of acute exacerbations, an

  15. Plasma sCD14 as a biomarker to predict pulmonary exacerbations in cystic fibrosis.

    Directory of Open Access Journals (Sweden)

    Bradley S Quon

    Full Text Available BACKGROUND: One in four cystic fibrosis (CF patients diagnosed with a pulmonary exacerbation will not recover their baseline lung function despite standard treatment. This highlights the importance of preventing such events. Clinical decision-making can be improved through a simple blood test that predicts individuals at elevated short-term risk of an exacerbation. METHODS: We obtained plasma samples from 30 stable CF patients from the St. Paul's Hospital Adult CF Clinic (Vancouver, Canada. For 15 patients, an additional plasma sample was obtained during an exacerbation. Soluble CD14 (sCD14 and C-reactive protein (CRP were quantified using ELISA kits. Myeloperoxidase (MPO, interleukin(IL-6, IL-1β, monocyte chemoattractant protein-1 (MCP-1, vascular endothelial growth factor (VEGF, and granulocyte colony-stimulating factor (G-CSF were quantified using Luminex™ immunoassays. Stable state biomarker levels were examined in their ability to predict individuals that would experience a pulmonary exacerbation requiring intravenous (IV antibiotics within 4 months. Paired stable and exacerbation plasma biomarker levels were also compared. RESULTS: sCD14 levels were significantly higher in patients that experienced a pulmonary exacerbation requiring IV antibiotics within 4 months (p = 0.001. sCD14 cut-off value of 1450 ng/mL was associated with an area under the curve of 0.91 (95% CI 0.83-0.99 for predicting an exacerbation within 4 months of a stable visit, with a sensitivity of 100% and specificity of 82%. Plasma sCD14 levels were significantly higher during exacerbations than during periods of clinical stability (p = 0.03. CONCLUSIONS: Plasma sCD14 is a promising biomarker for identifying CF patients who will exacerbate within 4 months of a stable visit but requires further study in larger, independent cohorts.

  16. Exacerbations of chronic obstructive pulmonary disease: when are antibiotics indicated? A systematic review

    Directory of Open Access Journals (Sweden)

    Steurer Johann

    2007-04-01

    Full Text Available Abstract Background For decades, there is an unresolved debate about adequate prescription of antibiotics for patients suffering from exacerbations of chronic obstructive pulmonary disease (COPD. The aim of this systematic review was to analyse randomised controlled trials investigating the clinical benefit of antibiotics for COPD exacerbations. Methods We conducted a systematic review of randomised, placebo-controlled trials assessing the effects of antibiotics on clinically relevant outcomes in patients with an exacerbation. We searched bibliographic databases, scrutinized reference lists and conference proceedings and asked the pharmaceutical industry for unpublished data. We used fixed-effects models to pool results. The primary outcome was treatment failure of COPD exacerbation treatment. Results We included 13 trials (1557 patients of moderate to good quality. For the effects of antibiotics on treatment failure there was much heterogeneity across all trials (I2 = 82%. Meta-regression revealed severity of exacerbation as significant explanation for this heterogeneity (p = 0.016: Antibiotics did not reduce treatment failures in outpatients with mild to moderate exacerbations (pooled odds ratio 1.09, 95% CI 0.75–1.59, I2 = 18%. Inpatients with severe exacerbations had a substantial benefit on treatment failure rates (pooled odds ratio of 0.25, 95% CI 0.16–0.39, I2 = 0%; number-needed to treat of 4, 95% CI 3–5 and on mortality (pooled odds ratio of 0.20, 95% CI 0.06–0.62, I2 = 0%; number-needed to treat of 14, 95% CI 12–30. Conclusion Antibiotics effectively reduce treatment failure and mortality rates in COPD patients with severe exacerbations. For patients with mild to moderate exacerbations, antibiotics may not be generally indicated and further research is needed to guide antibiotic prescription in these patients.

  17. Unemployment and substance use problems among young adults: Does childhood low socioeconomic status exacerbate the effect?

    Science.gov (United States)

    Lee, Jungeun Olivia; Hill, Karl G; Hartigan, Lacey A; Boden, Joseph M; Guttmannova, Katarina; Kosterman, Rick; Bailey, Jennifer A; Catalano, Richard F

    2015-10-01

    The current study tested whether unemployment predicted young adults' heavy episodic drinking, cigarette smoking, and cannabis use after taking into account individual development in substance use. Furthermore, building on the life course perspective, this study examined whether the link between unemployment and substance use among young adults differed for those who experienced low childhood SES compared to those who did not. Data for the present study came from the Seattle Social Development Project (SSDP), a panel study examining a broad range of developmental outcomes from ages 10 to 33. A life history calendar (LHC) was administered to assess substance use and unemployment status during young adulthood. Covariates included baseline symptoms of psychopathology, baseline substance use, gender, ethnicity, and adult educational attainment. Results suggest that unemployment is associated with young adults' heavy episodic drinking and possibly cigarette use, but not cannabis use. Moreover, for all three substances, the detrimental impact of unemployment on substance use seems to be exacerbated among young adults who spent their childhood and adolescence in a lower SES household. Public health efforts that provide other viable and affordable options to cope with unemployment among young adults from low SES backgrounds are needed to address this disproportionate concentration of adverse impacts of unemployment on behavioral health. PMID:26342911

  18. Acute effects of air pollution on pediatric asthma exacerbation: evidence of association and effect modification.

    Science.gov (United States)

    Samoli, E; Nastos, P T; Paliatsos, A G; Katsouyanni, K; Priftis, K N

    2011-04-01

    We investigated the short-term effects of particulate matter with aerodynamic diameter ozone (O(3)) on pediatric asthma emergency admissions in Athens, Greece over the period 2001-2004. We explored effect modification patterns by season, sex, age and by the presence of desert dust transported mainly from the Sahara area. We used daily time-series data provided by the children's hospitals and the fixed monitoring stations. The associations were investigated using Poisson regression models controlling for seasonality, weather, influenza episodes, day of the week and holiday effects. A 10 μg/m(3) increase in PM(10) was associated with a 2.54% increase (95% confidence interval (CI): 0.06%, 5.08%) in the number of pediatric asthma hospital admissions, while the same increase in SO(2) was associated with a 5.98% (95% CI: 0.88%, 11.33%) increase. O(3) was associated with a statistically significant increase in asthma admissions among older children in the summer. Our findings provide limited evidence of an association between NO(2) exposure and asthma exacerbation. Statistically significant PM(10) effects were higher during winter and during desert dust days, while SO(2) effects occurred mainly during spring. Our study confirms previously reported PM(10) effects on emergency hospital admissions for pediatric asthma and further provides evidence of stronger effects during desert dust days. We additionally report severe effects of SO(2), even at today's low concentration levels. PMID:21296347

  19. High-fat nutrition reduces hepatic damage following exposure to bacterial DNA and hemorrhagic shock.

    NARCIS (Netherlands)

    Luyer, M.D.; Derikx, J.P.; Beyaert, R.; Hadfoune, M.; Kuppevelt, A.H.M.S.M. van; Dejong, C.H.; Heineman, E.; Buurman, W.A.; Greve, J.W.

    2009-01-01

    BACKGROUND/AIMS: Bacterial infection combined with hypotension results in exacerbation of the inflammatory response with release of interferon (IFN) gamma. This excessive inflammation may lead to development of hepatic damage and liver failure. This study investigates the effect of dietary lipids on

  20. Neonatal androgenization exacerbates alcohol-induced liver injury in adult rats, an effect abrogated by estrogen.

    Directory of Open Access Journals (Sweden)

    Whitney M Ellefson

    Full Text Available Alcoholic liver disease (ALD affects millions of people worldwide and is a major cause of morbidity and mortality. However, fewer than 10% of heavy drinkers progress to later stages of injury, suggesting other factors in ALD development, including environmental exposures and genetics. Females display greater susceptibility to the early damaging effects of ethanol. Estrogen (E2 and ethanol metabolizing enzymes (cytochrome P450, CYP450 are implicated in sex differences of ALD. Sex steroid hormones are developmentally regulated by the hypothalamic-pituitary-gonadal (HPG axis, which controls sex-specific cycling of gonadal steroid production and expression of hepatic enzymes. The aim of this study was to determine if early postnatal inhibition of adult cyclic E2 alters ethanol metabolizing enzyme expression contributing to the development of ALD in adulthood. An androgenized rat model was used to inhibit cyclic E2 production. Control females (Ctrl, androgenized females (Andro and Andro females with E2 implants were administered either an ethanol or isocalorically-matched control Lieber-DeCarli diet for four weeks and liver injury and CYP450 expression assessed. Androgenization exacerbated the deleterious effects of ethanol demonstrated by increased steatosis, lipid peroxidation, profibrotic gene expression and decreased antioxidant defenses compared to Ctrl. Additionally, CYP2E1 expression was down-regulated in Andro animals on both diets. No change was observed in CYP1A2 protein expression. Further, continuous exogenous administration of E2 to Andro in adulthood attenuated these effects, suggesting that E2 has protective effects in the androgenized animal. Therefore, early postnatal inhibition of cyclic E2 modulates development and progression of ALD in adulthood.

  1. Immunohistochemical detection of virus through its nuclear cytopathic effect in idiopathic interstitial pneumonia other than acute exacerbation

    Directory of Open Access Journals (Sweden)

    G.C. dos Santos

    2013-11-01

    Full Text Available Idiopathic interstitial pneumonias include complex diseases that have a strong interaction between genetic makeup and environmental factors. However, in many cases, no infectious agent can be demonstrated, and these clinical diseases rapidly progress to death. Theoretically, idiopathic interstitial pneumonias could be caused by the Epstein-Barr virus, cytomegalovirus, adenovirus, hepatitis C virus, respiratory syncytial virus, and herpesvirus, which may be present in such small amounts or such configuration that routine histopathological analysis or viral culture techniques cannot detect them. To test the hypothesis that immunohistochemistry provides more accurate results than the mere histological demonstration of viral inclusions, this method was applied to 37 open lung biopsies obtained from patients with idiopathic interstitial pneumonias. As a result, immunohistochemistry detected measles virus and cytomegalovirus in diffuse alveolar damage-related histological patterns of acute exacerbation of idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia in 38 and 10% of the cases, respectively. Alveolar epithelium infection by cytomegalovirus was observed in 25% of organizing pneumonia patterns. These findings were coincident with nuclear cytopathic effects but without demonstration of cytomegalovirus inclusions. These data indicate that diffuse alveolar damage-related cytomegalovirus or measles virus infections enhance lung injury, and a direct involvement of these viruses in diffuse alveolar damage-related histological patterns is likely. Immunohistochemistry was more sensitive than the histological demonstration of cytomegalovirus or measles virus inclusions. We concluded that all patients with diffuse alveolar damage-related histological patterns should be investigated for cytomegalovirus and measles virus using sensitive immunohistochemistry in conjunction with routine procedures.

  2. Berry Fruit Supplementation in the Aging Brain

    Science.gov (United States)

    The onset of age-related neurodegenerative diseases such as Alzheimer’s or Parkinson’s Disease, superimposed on a declining nervous system, could exacerbate the motor and cognitive behavioral deficits that normally occur in senescence. In cases of severe deficits in memory or motor function, hospit...

  3. Management and prevention of chronic obstructive pulmonary disease exacerbations: a state of the art review

    Directory of Open Access Journals (Sweden)

    Wedzicha Jadwiga A

    2009-08-01

    Full Text Available Abstract Exacerbations of chronic obstructive pulmonary disease (COPD are important events in the natural history of this prevalent and devastating condition. This review provides a concise, state of the art summary on prevention and management of exacerbations. Considerable new data underpins evidence in support of many preventative interventions, pharmacological and non-pharmacological, that are now available. Challenges remain in developing new approaches, and delivering those that already exist to the right patient at the right time. Management of an exacerbation remains stepwise according to clinical severity, but there is now additional focus on addressing comorbidities and taking the opportunity at acute events to optimise preventative strategies for the future. Ultimately, exacerbations are heterogeneous events in a heterogeneous disease, and an individualised approach is paramount.

  4. CMTR1 is associated with increased asthma exacerbations in patients taking inhaled corticosteroids

    DEFF Research Database (Denmark)

    Dahlin, Amber; Denny, Joshua; Roden, Dan M;

    2015-01-01

    or emergency room visit. We hypothesized that some individuals may be at increased risk of asthma exacerbations, despite ICS use, due to genetic factors. A GWAS of 237,726 common, independent markers was conducted in 806 Caucasian asthmatic patients from two population-based biobanks: BioVU, at Vanderbilt...... candidate genes was determined by evaluating an independent microarray expression data set. Our study identified six novel SNPs associated with differential risk of asthma exacerbations (P risk of exacerbations in both...... populations (OR = 1.07, 95% CI 1.03-1.11; joint P = 2.3 × 10(-06)). Two SNPs (rs2395672 and rs279728) were associated with increased risk of exacerbations, while the remaining four SNPs (rs4271056, rs6467778, rs2691529, and rs9303988) were associated with decreased risk. Three SNPs (rs2395672, rs6467778...

  5. Bronchiectasis Exacerbations: The Role of Atypical Bacteria and Respiratory Syncytial Virus

    Directory of Open Access Journals (Sweden)

    Eugenios I Metaxas

    2015-01-01

    Full Text Available BACKGROUND: Aside from the known role of common bacteria, there is a paucity of data regarding the possible role of atypical bacteria and viruses in exacerbations of non-cystic fibrosis bronchiectasis.

  6. Climate change exacerbates interspecific interactions in sympatric coastal fishes.

    Science.gov (United States)

    Milazzo, Marco; Mirto, Simone; Domenici, Paolo; Gristina, Michele

    2013-03-01

    Biological responses to warming are presently based on the assumption that species will remain within their bioclimatic envelope as environmental conditions change. As a result, changes in the relative abundance of several marine species have been documented over the last decades. This suggests that warming may drive novel interspecific interactions to occur (i.e. invasive vs. native species) or may intensify the strength of pre-existing ones (i.e. warm vs. cold adapted). For mobile species, habitat relocation is a viable solution to track tolerable conditions and reduce competitive costs, resulting in 'winner' species dominating the best quality habitat at the expense of 'loser' species. Here, we focus on the importance of warming in exacerbating interspecific interactions between two sympatric fishes. We assessed the relocation response of the cool-water fish Coris julis (a potential 'loser' species in warming scenarios) at increasing relative dominance of the warm-water fish Thalassoma pavo (a 'winner' species). These wrasses are widespread in the Mediterranean nearshore waters. C. julis tolerates cooler waters and is found throughout the basin. T. pavo is common along southern coasts, although the species range is expanding northwards as the Mediterranean warms. We surveyed habitat patterns along a thermo-latitudinal gradient in the Western Mediterranean Sea and manipulated seawater temperature under two scenarios (present day vs. projected) in outdoor arenas. Our results show that the cool-water species relocates to a less-preferred seagrass habitat and undergoes lower behavioural performance in warmer environments, provided the relative dominance of its warm-water antagonist is high. The results suggest that expected warming will act synergistically with increased relative dominance of a warm-water species to cause a cool-water fish to relocate in a less-preferred habitat within the same thermal environment. Our study highlights the complexity of climate

  7. A score to predict short-term risk of COPD exacerbations (SCOPEX

    Directory of Open Access Journals (Sweden)

    Make BJ

    2015-01-01

    Full Text Available Barry J Make,1 Göran Eriksson,2 Peter M Calverley,3 Christine R Jenkins,4 Dirkje S Postma,5 Stefan Peterson,6 Ollie Östlund,7 Antonio Anzueto8 1Division of Pulmonary Sciences and Critical Care Medicine, National Jewish Health, University of Colorado Denver School of Medicine, Denver, CO, USA; 2Department of Respiratory Medicine and Allergology, University Hospital, Lund, Sweden; 3Pulmonary and Rehabilitation Research Group, University Hospital Aintree, Liverpool, UK; 4George Institute for Global Health, The University of Sydney and Concord Clinical School, Woolcock Institute of Medical Research, Sydney, NSW, Australia; 5Department of Pulmonology, University of Groningen and GRIAC Research Institute, University Medical Center Groningen, Groningen, The Netherlands; 6StatMind AB, Lund, Sweden; 7Department of Medical Sciences and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden; 8Department of Pulmonary/Critical Care, University of Texas Health Sciences Center and South Texas Veterans Healthcare System, San Antonio, TX, USA Background: There is no clinically useful score to predict chronic obstructive pulmonary disease (COPD exacerbations. We aimed to derive this by analyzing data from three existing COPD clinical trials of budesonide/formoterol, formoterol, or placebo in patients with moderate-to-very-severe COPD and a history of exacerbations in the previous year. Methods: Predictive variables were selected using Cox regression for time to first severe COPD exacerbation. We determined absolute risk estimates for an exacerbation by identifying variables in a binomial model, adjusting for observation time, study, and treatment. The model was further reduced to clinically useful variables and the final regression coefficients scaled to obtain risk scores of 0–100 to predict an exacerbation within 6 months. Receiver operating characteristic (ROC curves and the corresponding C-index were used to investigate the discriminatory

  8. COPD management costs according to the frequency of COPD exacerbations in UK primary care [Corrigendum

    OpenAIRE

    Punekar YS; Shukla A; Müllerova H

    2014-01-01

    Punekar YS, Shukla A, Müllerova H. International Journal of COPD. 2014;9:65–73.On page 69, note that there was an error in the bar graph shown in Figure 1. The group with no exacerbations during the 12 months of follow-up should have a zero value for the cost of exacerbations. The corrected figure is provided below.View original paper by Punekar and colleagues.

  9. Benefits of whole body vibration training in patients hospitalised for COPD exacerbations - a randomized clinical trial

    OpenAIRE

    Greulich, Timm; Nell, Christoph; Koepke, Janine; Fechtel, Juliane; Franke, Maja; Schmeck, Bernd; Haid, Daniel; Apelt, Sandra; Filipovic, Silke; Kenn, Klaus; Janciauskiene, Sabina; Vogelmeier, Claus; Koczulla, Andreas Rembert

    2014-01-01

    Background Patients with stable COPD show improvements in exercise capacity and muscular function after the application of whole body vibration. We aimed to evaluate whether this modality added to conventional physiotherapy in exacerbated hospitalised COPD patients would be safe and would improve exercise capacity and quality of life. Methods 49 hospitalised exacerbated COPD patients were randomized (1:1) to undergo physiotherapy alone or physiotherapy with the addition of whole body vibratio...

  10. Mechanisms and impact of the frequent exacerbator phenotype in chronic obstructive pulmonary disease

    OpenAIRE

    Wedzicha, J A; Brill, S E; Allinson, J. P.; Donaldson, G C

    2013-01-01

    Exacerbations of chronic obstructive pulmonary disease (COPD) are important events that carry significant consequences for patients. Some patients experience frequent exacerbations, and are now recognized as a distinct clinical subgroup, the ‘frequent exacerbator’ phenotype. This is relatively stable over time, occurs across disease severity, and is associated with poorer health outcomes. These patients are therefore a priority for research and treatment. The pathophysiology underlying the fr...

  11. Review of ventilatory techniques to optimize mechanical ventilation in acute exacerbation of chronic obstructive pulmonary disease

    OpenAIRE

    Reddy, Raghu M.; Guntupalli, Kalpalatha K.

    2007-01-01

    Chronic obstructive pulmonary disease (COPD) is a major global healthcare problem. Studies vary widely in the reported frequency of mechanical ventilation in acute exacerbations of COPD. Invasive intubation and mechanical ventilation may be associated with significant morbidity and mortality. A good understanding of the airway pathophysiology and lung mechanics in COPD is necessary to appropriately manage acute exacerbations and respiratory failure. The basic pathophysiology in COPD exacerbat...

  12. Comparison of Canadian versus United States Emergency Department Visits for Chronic Obstructive Pulmonary Disease Exacerbation

    OpenAIRE

    Rowe, Brian H; Rita K Cydulka; Chu-Lin Tsai; Sunday Clark; Douglas Sinclair; Camargo, Carlos A.

    2008-01-01

    INTRODUCTION: Despite the frequency of emergency department (ED) visits for chronic obstructive pulmonary disease (COPD) exacerbation, little is known about practice variation in EDs.OBJECTIVES: To examine the differences between Canadian and United States (US) COPD patients, and the ED management they receive.METHODS: A prospective multicentre cohort study was conducted involving 29 EDs in the US and Canada. Using a standard protocol, consecutive ED patients with COPD exacerbations were inte...

  13. Analgesia and Addiction in Emergency Department Patients with Acute Pain Exacerbations

    OpenAIRE

    Gorchynski, Julie; Kelly, Kevin

    2005-01-01

    Introduction: There is ongoing controversy regarding the appropriate use of narcotic analgesia for patients presenting frequently to the emergency department (ED) with subjective acute exacerbations of pain. "Are we treating pain or enabling addiction?” Objectives: To determine whether the presence o f specific factors could be used to identify adults complaining of acute exacerbations of pain for suspected drug addiction, to estimate the percentage of drug addicted patients, to asse...

  14. The Most Common Detected Bacteria in Sputum of Patients with the Acute Exacerbation of COPD

    OpenAIRE

    Cukic, Vesna

    2013-01-01

    Introduction: Acute exacerbation of COPD (AECOPD) may be triggered by infection with bacteria or viruses or by environmental pollutants; the cause of about one-third of exacerbations cannot be identified. Objective: To determine the most common bacteria in sputum culture of patients with AECOPD hospitalized in Intensive care unit of Clinic for pulmonary disease and TB “Podhrastovi” in the 2012. Material and methods: This is a retrospective analysis of sputum bacterial cultures of patients wit...

  15. Activation of cerebral sodium-glucose transporter type 1 function mediated by post-ischemic hyperglycemia exacerbates the development of cerebral ischemia.

    Science.gov (United States)

    Yamazaki, Y; Ogihara, S; Harada, S; Tokuyama, S

    2015-12-01

    The regulation of post-ischemic hyperglycemia plays an important role in suppressing neuronal damage in therapeutic strategies for cerebral ischemia. We previously reported that the cerebral sodium-glucose transporter (SGLT) was involved in the post-ischemic hyperglycemia-induced exacerbation of cerebral ischemic neuronal damage. Cortical SGLT-1, one of the cerebral SGLT isoforms, is dramatically increased by focal cerebral ischemia. In this study, we focused on the involvement of cerebral SGLT-1 in the development of cerebral ischemic neuronal damage. It was previously reported that activation of 5'-adenosine monophosphate-activated protein kinase (AMPK) increases SGLT-1 expression. Moreover, ischemic stress-induced activation of AMPK exacerbates cerebral ischemic neuronal damage. Therefore, we directly confirmed the relationship between cerebral SGLT-1 and cerebral AMPK activation using in vitro primary culture of mouse cortical neurons. An in vivo mouse model of focal cerebral ischemia was generated using a middle cerebral artery occlusion (MCAO). The development of infarct volume and behavioral abnormalities on day 3 after MCAO were ameliorated in cerebral SGLT-1 knock down mice. Cortical and striatal SGLT-1 expression levels were significantly increased at 12h after MCAO. Immunofluorescence revealed that SGLT-1 and the neuronal nuclear antigen (NeuN) were co-localized in the cortex and striatum of MCAO mice. In the in vitro study, primary cortical neurons were cultured for five days before each treatment with reagents. Concomitant treatment with hydrogen peroxide and glucose induced the elevation of SGLT-1 and phosphorylated AMPK/AMPK ratio, and this elevation was suppressed by compound C, an AMPK inhibitor in primary cortical neurons. Moreover, compound C suppressed neuronal cell death induced by concomitant hydrogen peroxide/glucose treatment in primary cortical neurons. Therefore, we concluded that enhanced cerebral SGLT-1 function mediated by post

  16. LOCA testing of damaged cables

    International Nuclear Information System (INIS)

    Experiments were conducted to assess the effects of dielectric withstand voltage testing of cables and to assess the survivability of aged and damaged cables under loss-of-coolant accident (LOCA) conditions. High potential testing at 240 Vdc/mil on undamaged cables suggested that no damage was incurred on the selected cables. During aging and LOCA testing, Okonite ethylene propylene rubber cables with a bonded jacket experienced unexpected failures. The failures appear to be primarily related to the level of thermal aging. For Brand Rex crosslinked polyolefin cables, the results suggest that 8 mils of insulation remaining should give the cables a high probability of surviving accident exposure following aging. The voltage levels necessary to detect when 8 mils of insulation remain are expected to be roughly 40 kVdc. This voltage level would almost certainly be unacceptable to a utility for use as a damage assessment tool. Although two Rockbestos silicone rubber cables failed during the accident test, the induced wall thickness did not seem to be the major cause of the failures. It appears likely that under less stressful thermal aging conditions, the cables would survive accident testing with as little as 4 mils or less of insulation remaining

  17. An experimental model of rhinovirus induced chronic obstructive pulmonary disease exacerbations: a pilot study

    Directory of Open Access Journals (Sweden)

    Mallia Patrick

    2006-09-01

    Full Text Available Abstract Background Acute exacerbations of COPD are a major cause of morbidity, mortality and hospitalisation. Respiratory viruses are associated with the majority of exacerbations but a causal relationship has not been demonstrated and the mechanisms of virus-induced exacerbations are poorly understood. Development of a human experimental model would provide evidence of causation and would greatly facilitate understanding mechanisms, but no such model exists. Methods We aimed to evaluate the feasibility of developing an experimental model of rhinovirus induced COPD exacerbations and to assess safety of rhinovirus infection in COPD patients. We carried out a pilot virus dose escalating study to assess the minimum dose of rhinovirus 16 required to induce experimental rhinovirus infection in subjects with COPD (GOLD stage II. Outcomes were assessed by monitoring of upper and lower respiratory tract symptoms, lung function, and virus replication and inflammatory responses in nasal lavage. Results All 4 subjects developed symptomatic colds with the lowest dose of virus tested, associated with evidence of viral replication and increased pro-inflammatory cytokines in nasal lavage. These were accompanied by significant increases in lower respiratory tract symptoms and reductions in PEF and FEV1. There were no severe exacerbations or other adverse events. Conclusion Low dose experimental rhinovirus infection in patients with COPD induces symptoms and lung function changes typical of an acute exacerbation of COPD, appears safe, and provides preliminary evidence of causation.

  18. The role of fluticasone propionate/salmeterol combination therapy in preventing exacerbations of COPD

    Directory of Open Access Journals (Sweden)

    Barbara P Yawn

    2010-06-01

    Full Text Available Barbara P Yawn1, Ibrahim Raphiou2, Judith S Hurley3, Anand A Dalal21Olmsted Medical Center, University of Minnesota, Rochester, Minnesota, USA; 2GlaxoSmithKline, Research Triangle Park, North Carolina, USA; 3Hurley Consulting, Placitas, New Mexico, USAAbstract: Exacerbations contribute significantly to the morbidity of COPD, leading to an accelerated decline in lung function, reduced functional status, reduced health status and quality of life, poorer prognosis and increased mortality. Prevention of exacerbations is thus an important goal of COPD management. In patients with COPD, treatment with a combination of the inhaled corticosteroid fluticasone propionate (250 μg and the long-acting β2-agonist salmeterol (50 μg in a single inhaler (250/50 μg is an effective therapy option that has been shown to reduce the frequency of exacerbations, to improve lung function, dyspnea and health status, and to be relatively cost-effective as a COPD maintenance therapy. Importantly, results of various studies suggest that fluticasone propionate and salmeterol have synergistic effects when administered together that improve their efficacy in controlling symptoms and reducing exacerbations. The present non-systematic review summarizes the role of fluticasone propionate/salmeterol combination therapy in the prevention of exacerbations of COPD and its related effects on lung function, survival, health status, and healthcare costs.Keywords: Advair, COPD, disease exacerbation, fluticasone propionate, salmeterol, combination drug therapy

  19. Bronchiectasis exacerbations: The role of atypical bacteria and respiratory syncytial virus

    Science.gov (United States)

    Metaxas, Eugenios I; Balis, Evangelos; Papaparaskevas, Joseph; Spanakis, Nicholas E; Tatsis, Georgios; Tsakris, Athanasios

    2015-01-01

    BACKGROUND: Aside from the known role of common bacteria, there is a paucity of data regarding the possible role of atypical bacteria and viruses in exacerbations of non-cystic fibrosis bronchiectasis. OBJECTIVE: To explore the possible role of atypical bacteria (namely, Mycoplasma pneumoniae and Chlamydophila pneumoniae) and respiratory syncytial virus (RSV) as causative agents of bronchiectasis exacerbations. METHODS: A cohort of 33 patients was studied over a two-year period (one year follow-up for each patient). Polymerase chain reaction for the detection of M pneumoniae, C pneumoniae and RSV in bronchoalveolar lavage samples were performed during all visits. Antibody titres (immunoglobulin [Ig]M and IgG) against the aforementioned pathogens were also measured. In addition, cultures for common bacteria and mycobacteria were performed from the bronchoalveolar lavage samples. RESULTS: Fifteen patients experienced a total of 19 exacerbations during the study period. Although RSV was detected by polymerase chain reaction during stable visits in four patients, it was never detected during an exacerbation. M pneumoniae and C pneumoniae were never detected at stable visits or during exacerbations. IgM antibody titres for these three pathogens were negative in all patient visits. CONCLUSIONS: Atypical pathogens and RSV did not appear to be causative agents of bronchiectasis exacerbations. PMID:25874735

  20. Targeting Protective Autophagy Exacerbates UV-Triggered Apoptotic Cell Death

    Directory of Open Access Journals (Sweden)

    Shih-Hwa Chiou

    2012-01-01

    Full Text Available Autophagy is activated by various stresses, including DNA damage, and previous studies of DNA damage-induced autophagy have focused on the response to chemotherapeutic drugs, ionizing radiation, and reactive oxygen species. In this study, we investigated the biological significance of autophagic response to ultraviolet (UV irradiation in A549 and H1299 cells. Our results indicated that UV induces on-rate autophagic flux in these cells. Autophagy inhibition resulting from the knockdown of beclin-1 and Atg5 reduced cell viability and enhanced apoptosis. Moreover, we found that ATR phosphorylation was accompanied by microtubule-associated protein 1 light chain 3B II (LC3B-II expression during the early phases following UV irradiation, which is a well-established inducer of ATR. Knocking down ATR further attenuated the reduction in LC3B-II at early stages in response to UV treatment. Despite the potential role of ATR in autophagic response, reduced ATR expression does not affect autophagy induction during late phases (24 and 48 h after UV treatment. The result is consistent with the reduced ATR phosphorylation at the same time points and suggests that autophagic response at this stage is activated via a distinct pathway. In conclusion, this study demonstrated that autophagy acts as a cytoprotective mechanism against UV-induced apoptosis and that autophagy induction accompanied with apoptosis at late stages is independent of ATR activation.

  1. The decline in pulsatile GH secretion throughout early adulthood in mice is exacerbated by dietary-induced weight gain.

    Science.gov (United States)

    Huang, L; Steyn, F J; Tan, H Y; Xie, T Y; Veldhuis, J D; Ngo, S T; Chen, C

    2012-09-01

    The transition between puberty and adulthood is accompanied by a slowing in linear growth. Although GH is a key factor that drives somatic development into adulthood, early adulthood coincides with a reduction in circulating levels of GH. To this extent, a pathological decline in postpubertal GH secretion is detrimental to attainment of peak lean muscle mass and bone mass and promotes adiposity and increases susceptibility to the development of obesity in adulthood. Here we characterized pulsatile GH secretion in C57BL/6J mice at 12 and 16 wk of age. Deconvolution analysis of these measures reveals a reduction in pulsatile GH secretion between 12 and 16 wk of age. Dietary intervention with high-fat feeding at 8 wk of age results in a significant increase in adiposity, the development of glucose intolerance, and hyperinsulinemia. We show the exacerbation of the age-associated decline in pulsatile GH secretion in high-fat-fed mice after 4 wk of dietary intervention (at 12 wk of age), and a further suppression of pulsatile GH secretion by 8 wk of dietary intervention (at 16 wk of age). Suppressed pulsatile secretion of GH did not coincide with an elevation in circulating free fatty acids. Rather, we observed increased hepatic triglyceride content and an eventual decrease in circulating levels of IGF-I. Given the established role of GH in maintaining healthy aging, we anticipate that an advancing of the age-associated decline in pulsatile GH secretion as a consequence of dietary-induced weight gain may have long-term ramifications on adult health. PMID:22802464

  2. Use of non-invasive ventilation is increasing in patients admitted with a chronic obstructive pulmonary disease exacerbation

    DEFF Research Database (Denmark)

    Tøttenborg, Sandra Søgaard; Johnsen, Søren Paaske; Thomsen, Reimar Wernich;

    2013-01-01

    INTRODUCTION: A nationwide chronic obstructive pulmonary disease (COPD) quality improvement programme - DrCOPD - was initiated in Denmark in 2008. We examined subsequent national and regional trends in the use of non-invasive ventilation (NIV) and trends in mortality following NIV and invasive...... mechanical ventilation among patients acutely admitted with a COPD exacerbation. MATERIALS AND METHODS: We did a nationwide, population-based prospective study using DrCOPD to identify all incident hospitalizations with COPD from 2008 through 2011 (n = 24,982) and to record the use of NIV during.......8% to 7.0% (adjusted for age, sex and co-morbidity, relative risk (RR): 1.21, 95% confidence interval (CI): 1.05-1.38). Concurrently, a statistically significant increase from 1.3% to 1.8% (RR: 1.36; 95% CI: 1.03-1.80) in NIV given together with invasive mechanical ventilation was observed. During the...

  3. Treatment and evaluation of patients with acute exacerbation of asthma before and during a visit to the ER in Denmark

    DEFF Research Database (Denmark)

    Backer, V.; Harving, H.; Soes-Petersen, U.;

    2008-01-01

    leading to admission. Material and methods: In a retrospective design, we audited the hospital records of all patients aged 18-40 years admitted to five Danish university hospitals with an acute exacerbation of asthma in 2004. Results: We found records covering 323 asthmatic patients (186 women). Before...... forced expiratory volume in first second) was measured in 60% on admission, in 58% on discharge and in 47% on both occasions (P < 0.01). Temperature, heart rate and oxygen saturation were measured in 231 of the patients (72%), but the respiratory frequency rate was measured in only 16% of the patients......, with some differences between the five hospitals. On discharge, 50% were treated with systemic steroids, and a further 20% had ICS prescribed (P < 0.01, admission vs discharge). In 21% of the cases, inadequate treatment was identified as the most likely reason for their ER visit/admission to a hospital...

  4. Management and survival of patients admitted with an exacerbation of COPD: comparison of two Danish patient cohorts

    DEFF Research Database (Denmark)

    Eriksen, Nanna; Vestbo, Jørgen

    2010-01-01

    discharged patients admitted in 2006-2007 with an exacerbation of chronic obstructive pulmonary disease from three respiratory departments. Data were collected from patient charts and compared with a replicate study done in 2001. RESULTS: The mean age was 72.1years; 61.7% were women. Mean forced expiratory...... volume in 1s was 37.6% of predicted. On admission, 11.3% were treated with non-invasive ventilation, and 84.3% were given systemic corticosteroids. In-hospital mortality was 4.7%. At discharge, treatment with inhaled corticosteroids or at least one long-acting bronchodilator was given to 86.7% and 89% of......months following discharge was 42.3%. Long-term oxygen treatment, treatment with anti-dysrhythmic drugs and lack of outpatient follow-up were independent predictors of 1-year mortality. Risk of readmission was increased with dependence in self-care activities, previous admissions and treatment with...

  5. Prevention of COPD exacerbation by lysozyme: a double-blind, randomized, placebo-controlled study

    Directory of Open Access Journals (Sweden)

    Fukuchi Y

    2016-04-01

    Full Text Available Yoshinosuke Fukuchi,1 Koichiro Tatsumi,2 Hiromasa Inoue,3 Yukinori Sakata,4 Kai Shibata,4 Hideaki Miyagishi,4 Yasuhiro Marukawa,4 Masakazu Ichinose5 1Department of Respiratory Medicine, Graduate School of Medicine, Juntendo University, Tokyo, 2Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, 3Department of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, 4Eisai Co., Ltd., Tokyo, 5Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan Background/aim: Lysozyme (mucopeptide N-acetyl-muramyl hydrolase is widely used as a mucolytic and anti-inflammatory agent in Japan. We evaluated the effects of long-term lysozyme administration on COPD exacerbation. Methods: In a 1-year, randomized, double-blind, placebo-controlled, parallel trial, patients with moderate-to-severe COPD and one or more episodes of COPD exacerbation in the previous year before enrollment were selected. Lysozyme (270 mg or placebo was administered orally for 52 weeks as an add-on to the standard therapies such as bronchodilators. COPD exacerbation, pulmonary function, and COPD assessment test scores were analyzed. An exacerbation was defined as worsening of more than one symptom of COPD (cough, sputum volume, purulent sputum, or breathlessness leading to a change in medication. The primary endpoint was exacerbation rate. Results: A total of 408 patients were randomly assigned to the lysozyme and placebo groups. The baseline characteristics were similar between the two groups. The exacerbation rate was not significantly different between the two groups (1.4 vs 1.2; P=0.292, Poisson regression. However, a subgroup analysis showed that lysozyme might reduce exacerbation rate in patients with airway-dominant phenotype (1.2 vs 1.6. Moreover, the median time to first exacerbation was longer in patients with airway-dominant phenotype in the lysozyme group than that

  6. Systemic carnitine deficiency exacerbated by a strict vegetarian diet.

    OpenAIRE

    Etzioni, A.; Levy, J; Nitzan, M; Erde, P; Benderly, A

    1984-01-01

    A 12-year old boy suffered episodes of vomiting, lethargy, and hypoglycaemia from the age of 1 year. Adhering to a vegetarian diet caused an increase in frequency and severity of the attacks. It was found that he was suffering from systemic carnitine deficiency that responded promptly to treatment with L-carnitine.

  7. Biology of ageing

    DEFF Research Database (Denmark)

    Rattan, Suresh

    2015-01-01

    Living systems owe their survival and health to a series of complex biochemical pathways of maintenance and repair. These defense systems create the homeodynamic space of an individual, which is characterized by stress tolerance, molecular damage control and continuous remodeling. Ageing, age-rel...

  8. Sleep Deprivation-Induced Blood-Brain Barrier Breakdown and Brain Dysfunction are Exacerbated by Size-Related Exposure to Ag and Cu Nanoparticles. Neuroprotective Effects of a 5-HT3 Receptor Antagonist Ondansetron.

    Science.gov (United States)

    Sharma, Aruna; Muresanu, Dafin F; Lafuente, José V; Patnaik, Ranjana; Tian, Z Ryan; Buzoianu, Anca D; Sharma, Hari S

    2015-10-01

    Military personnel are often subjected to sleep deprivation (SD) during combat operations. Since SD is a severe stress and alters neurochemical metabolism in the brain, a possibility exists that acute or long-term SD will influence blood-brain barrier (BBB) function and brain pathology. This hypothesis was examined in young adult rats (age 12 to 14 weeks) using an inverted flowerpot model. Rats were placed over an inverted flowerpot platform (6.5 cm diameter) in a water pool where the water levels are just 3 cm below the surface. In this model, animals can go to sleep for brief periods but cannot achieve deep sleep as they would fall into water and thus experience sleep interruption. These animals showed leakage of Evans blue in the cerebellum, hippocampus, caudate nucleus, parietal, temporal, occipital, cingulate cerebral cortices, and brain stem. The ventricular walls of the lateral and fourth ventricles were also stained blue, indicating disruption of the BBB and the blood-cerebrospinal fluid barrier (BCSFB). Breakdown of the BBB or the BCSFB fluid barrier was progressive in nature from 12 to 48 h but no apparent differences in BBB leakage were seen between 48 and 72 h of SD. Interestingly, rats treated with metal nanoparticles, e.g., Cu or Ag, showed profound exacerbation of BBB disruption by 1.5- to 4-fold, depending on the duration of SD. Measurement of plasma and brain serotonin showed a close correlation between BBB disruption and the amine level. Repeated treatment with the serotonin 5-HT3 receptor antagonist ondansetron (1 mg/kg, s.c.) 4 and 8 h after SD markedly reduced BBB disruption and brain pathology after 12 to 24 h SD but not following 48 or 72 h after SD. However, TiO2-nanowired ondansetron (1 mg/kg, s.c) in an identical manner induced neuroprotection in rats following 48 or 72 h SD. However, plasma and serotonin levels were not affected by ondansetron treatment. Taken together, our observations are the first to show that (i) SD could induce BBB

  9. Monitoring ageing of components in nuclear plants

    International Nuclear Information System (INIS)

    There are several mechanisms of ageing or damage in nuclear components, of which the best known can be classified into three categories: generalized damage mechanisms (wear, corrosion, erosion,...), local damage phenomena (fatigue, corrosion,...) and material property degradations. For ageing evaluation, the first requirement is a good understanding of the damage mechanisms and the determination of the kinetic laws and major influencing factors. When these factors are measurable physical parameters, ageing monitoring and periodic evaluation of damage level become possible. From the set of tools available for ageing evaluation, four are presented here in more detail: the transient logging procedure, the defect injuriousness analysis, the fatigue meter, the probabilistic approach to structural integrity. (author)

  10. Determining the diagnostic value of endogenous carbon monoxide in Chronic Obstructive Pulmonary Disease exacerbations

    International Nuclear Information System (INIS)

    Objective: To determine whether endogenous carbon monoxide levels in exacerbations of Chronic Obstructive Pulmonary Disease patients were higher compared to healthy individuals and to investigate alteration of carbon monoxide levels across the three different severity stages of Global Initiative for Chronic Obstructive Lung Disease criteria related to Chronic Obstructive Pulmonary Disease exacerbations. Methods: The prospective study was conducted from January to March 2011 at two medical institutions in Ankara, Turkey, and comprised patients of acute Chronic Obstructive Pulmonary Disease exacerbations. The severity of the exacerbations was based on the Global Initiative for Chronic Obstructive Lung Disease criteria. Patients with active tobacco smoking, suspicious carbon monoxide poisoning and uncertain diagnosis were excluded. healthy control subjects who did not have any comorbid diseases and smoking habitus were also enrolled to compare the differences between carboxyhaemoglobin levels A two-tailed Mann-Whitney U test with Bonferroni correction was done following a Kruskal-Wallis test for statistical purposes. Results: There were 90 patients and 81 controls in the study. Carboxyhaemoglobin levels were higher in the patients than the controls (p<0.001). As for the three severity stages, Group 1 had a median carboxyhaemoglobin of 1.6 (0.95-2.00). The corresponding levels in Group 2 (1.8 (1.38-2.20)) and Group 3 (1.9 (1.5-3.0)) were higher than the controls (p<0.001 and p<0.005 respectively). No statistically significant difference between Group 1 and the controls (1.30 (1.10-1.55)) was observed (p<0.434). Conclusion: Carboxyhaemoglobin levels were significantly higher in exacerbations compared with the normal population. Also, in more serious exacerbations, carboxyhaemoglobin levels were significantly increased compared with healthy individuals and mild exacerbations. (author)

  11. Do metals that translocate to the brain exacerbate traumatic brain injury?

    Science.gov (United States)

    Kalinich, John F; Kasper, Christine E

    2014-05-01

    Metal translocation to the brain is strictly controlled and often prevented by the blood-brain barrier. For the most part, only those metals required to maintain normal function are transported into the brain where they are under tight metabolic control. From the literature, there are reports that traumatic brain injury disrupts the blood-brain barrier. This could allow the influx of metals that would normally have been excluded from the brain. We also have preliminary data showing that metal pellets, surgically-implanted into the leg muscle of a rat to simulate a shrapnel wound, solubilize and the metals comprising the pellet can enter the brain. Surprisingly, rats implanted with a military-grade tungsten alloy composed of tungsten, nickel, and cobalt also showed significantly elevated uranium levels in their brains as early as 1 month after pellet implantation. The only source of uranium was low levels that are naturally found in food and water. Conversely, rats implanted with depleted uranium pellets demonstrated elevated uranium levels in brain resulting from degradation of the implanted pellets. However, when cobalt levels were measured, there were no significant increases in the brain until the rats had reached old age. The only source of cobalt for these rats was the low levels found in their food and water. These data suggest that some metals or metal mixtures (i.e., tungsten alloy), when embedded into muscle, can enhance the translocation of other, endogenous metals (e.g., uranium) across the blood-brain barrier. For other embedded metals (i.e., depleted uranium), this effect is not observed until the animal is of advanced age. This raises the possibility that metal body-burdens can affect blood-brain barrier permeability in a metal-specific and age-dependent manner. This possibility is disconcerting when traumatic brain injury is considered. Traumatic brain injury has been called the "signature" wound of the conflicts in Iraq and Afghanistan, often, an

  12. Excavation damaged zone

    Energy Technology Data Exchange (ETDEWEB)

    Popp, T.; Salzer, K.; Minkley, W. [Institut fur Gebirgsmechanik GmbH, Leipzig (Germany); Gibert, D.; Nicollin, F.; Kergosien, B. [Rennes-1 Univ., GdR FORPRO (CNRS/ANDRA GdR 788) and Geosciences Rennes (CNRS/UR1 UMR 6118) (France); Bossart, P. [Federal Office for Topography, Wabern (Switzerland); Nussbaum, C. [Institut Geotechnique SA, St-Ursanne (Switzerland); Robinet, J.C.; Nguyen, M.T. [EGC Euro-Geomat-Consulting, 45 - Orleans (France); Barnichon, J.D.; Plas, F. [ANDRA - Agence Nationale pour la Gestion des Dechets Radioactifs, 92 - Chatenay Malabry (France); Ghorbani, A.; Cosenza, P.; Florsch, N. [Pierre et Marie Curie Univ., UMR 7619 Sisyphe, 75 - Paris (France); Revil, A.; Jougnot, D. [Aix-Marseille-2, UMR 6635, CNRS-CEREGE, 13 (France); Schmutz, M. [EGID, M. de Montaigne Univ., 33 - Pessac (France); Contrucci, I.; Klein, E. [Institut National de l' Environnement Industriel et des Risques (INERIS), Ecole des Mines de Nancy, 54 - Nancy (France); Cabrera, J.; Ben-Slimane, K.; Rejeb, A.; Matray, J.M.; Savoye, S. [Institut de Radioprotection et de Surete Nucleaire (IRSN), 92 - Fontenay-aux-Roses (France); Maiolino, S. [Ecole Polytechnique, Lab. de Mecanique des Solides, UMR 7649, LMS, 91 - Palaiseau (France); CETE de Lyon/LRPC de Lyon/Meca Roches/ ERA, 69 - Bron (France); Yong, S.; Loew, S.; Fidelibus, C.; Lemy, F. [Engineering Geology, ETH Zurich, Zurich (Switzerland); Frank, E. [Swiss Federal Nuclear Safety Inspectorate (HSK), Villigen (Switzerland); Chun-Liang, Zhang; Tilmann, Rothfuchs [Gesellschaft fur Anlagen- und Reaktorsicherheit (GRS) mbH, Braunschweig (Germany)

    2007-07-01

    This session gathers 10 articles (posters) dealing with: the influence of bedding planes to EDZ evolution and the coupled HM properties of Opalinus Clay; the electrical tomography monitoring of the EDZ during the excavation of the gallery 04 in the Mont Terri rock laboratory; the seismic endoscopy and tomography of the EDZ of the gallery 04 in the Mont Terri rock laboratory; a elastoplastic damage model for saturated and unsaturated stiffness clays: description and application to the modelling of EDZ around drifts in Callovo-Oxfordian argillites; the non-invasive monitoring of water content and microcracks in argillites using spectral induced polarization; EDZ investigations by ultrasonic borehole logging in drifts of different ages excavated in argillaceous formations of the Tournemire experimental station (Aveyron, France); the excavation damaged zones in the argillaceous Tournemire site: characterisation and failure mechanisms; the hardening-based degradation factor: influence of mean stress and stiffness; the disturbance in the EDZ in the Opalinus clay at Mont Terri; and the experimental study on self-sealing capacity of clay rocks.

  13. Two 6-minute Walk Tests Are Required During Hospitalisation for Acute Exacerbation of COPD.

    Science.gov (United States)

    Osadnik, Christian R; Borges, Rodrigo C; McDonald, Christine F; Carvalho, Celso R F; Holland, Anne E

    2016-06-01

    The 6-minute walk test (6MWT) is recommended to be performed twice to accurately assess exercise performance in stable chronic obstructive pulmonary disease (COPD) due to the presence of a learning effect. It is unknown whether a learning effect exists when the 6MWT is performed during hospitalisation for acute exacerbation of COPD (AECOPD). This study investigated whether repeat 6MWTs are necessary when conducted in inpatients with AECOPD. Pooled analysis was undertaken of data from two studies (Australia and Brazil) involving 46 participants (25 males, mean age 67.2 years, FEV1 43% predicted) admitted with AECOPD. Two 6MWTs, separated by ≥20 minutes, were performed on the day of discharge. Six-minute walk distance (6MWD; primary outcome), perceived dyspnoea (Borg scale), heart rate and oxyhaemoglobin saturation were recorded. 6MWD data from tests one (T1) and two (T2) were analysed via visual inspection of Bland-Altman plots. Factors associated with test improvement or decline were explored. Mean 6MWD difference between T1 and T2 was 6.2 m, however limits of agreement were wide (-92.2 m to 104.5 m). 32 (70%) participants improved (by any distance) from T1 to T2 by a mean (± standard deviation) of 32 m ± 28 m. Of these, 14 (30%) improved by a distance > 30 m. Fourteen (30%) participants recorded poorer 6MWD at T2 by a mean of 52 m ± 36 m. No factors were able to identify participants who improved or declined upon repeat testing. When performed in patients admitted to hospital with AECOPD, the 6MWT needs to be conducted twice in order to better estimate 6MWD. PMID:26643192

  14. Chloroquine and its derivatives exacerbate B19V-associated anemia by promoting viral replication.

    Directory of Open Access Journals (Sweden)

    Claudia Bönsch

    Full Text Available BACKGROUND: An unexpectedly high seroprevalence and pathogenic potential of human parvovirus B19 (B19V have been observed in certain malaria-endemic countries in parallel with local use of chloroquine (CQ as first-line treatment for malaria. The aims of this study were to assess the effect of CQ and other common antimalarial drugs on B19V infection in vitro and the possible epidemiological consequences for children from Papua New Guinea (PNG. METHODOLOGY/PRINCIPAL FINDINGS: Viral RNA, DNA and proteins were analyzed in different cell types following infection with B19V in the presence of a range of antimalarial drugs. Relationships between B19V infection status, prior 4-aminoquinoline use and anemia were assessed in 200 PNG children <10 years of age participating in a case-control study of severe infections. In CQ-treated cells, the synthesis of viral RNA, DNA and proteins was significantly higher and occurred earlier than in control cells. CQ facilitates B19V infection by minimizing intracellular degradation of incoming particles. Only amodiaquine amongst other antimalarial drugs had a similar effect. B19V IgM seropositivity was more frequent in 111 children with severe anemia (hemoglobin <50 g/L than in 89 healthy controls (15.3% vs 3.4%; P = 0.008. In children who were either B19V IgM or PCR positive, 4-aminoquinoline use was associated with a significantly lower admission hemoglobin concentration. CONCLUSIONS/SIGNIFICANCE: Our data strongly suggest that 4-aminoquinoline drugs and their metabolites exacerbate B19V-associated anemia by promoting B19V replication. Consideration should be given for choosing a non-4-aminoquinoline drug to partner artemisinin compounds in combination antimalarial therapy.

  15. Pulmonary rehabilitation and severe exacerbations of COPD: solution or white elephant?

    Directory of Open Access Journals (Sweden)

    William D-C. Man

    2015-10-01

    Full Text Available Hospitalisations for severe exacerbations of chronic obstructive pulmonary disease are associated with significant physical and psychological consequences including an increase in symptom severity, severe reductions in physical activity, a deleterious effect on skeletal muscle, impaired exercise tolerance/ability to self-care, decline in quality of life, and increased anxiety and depression. As these consequences are potentially amenable to exercise training, there is a clear rationale for pulmonary rehabilitation in the peri/post-exacerbation setting. Although a 2011 Cochrane review was overwhelmingly positive, subsequent trials have shown less benefit and real-life observational studies have revealed poor acceptability. Qualitative studies have demonstrated that the patient experience is a determining factor while the presence of comorbidities may influence referral, adherence and response to pulmonary rehabilitation. Systematic reviews of less supervised interventions, such as self-management, have shown limited benefits in the post-exacerbation setting. The recent update of the Cochrane review of peri-exacerbation pulmonary rehabilitation showed that benefits were associated with the “comprehensive” nature of the intervention (the number of sessions received, the intensity of exercise training and education delivered, and the degree of supervision but implementation is demanding. The challenge is to develop interventions that are deliverable and acceptable around the time of an acute exacerbation but also deliver the desired clinical impact.

  16. We Are Ageing

    OpenAIRE

    Kolovou, Genovefa D; Kolovou, Vana; Mavrogeni, Sophie

    2014-01-01

    Ageing and longevity is unquestioningly complex. Several thoughts and mechanisms of ageing such as pathways involved in oxidative stress, lipid and glucose metabolism, inflammation, DNA damage and repair, growth hormone axis and insulin-like growth factor (GH/IGF), and environmental exposure have been proposed. Also, some theories of ageing were introduced. To date, the most promising leads for longevity are caloric restriction, particularly target of rapamycin (TOR), sirtuins, hexarelin and ...

  17. The feasibility of a home-based sedentary behaviour intervention for hospitalised chronic obstructive pulmonary disease (COPD patients: Sitting and ExacerbAtions Trial (COPD-SEAT

    Directory of Open Access Journals (Sweden)

    Mark Orme

    2015-10-01

    COPD-SEAT will be one of the first trials aimed at reducing sedentary behaviour at home in patients hospitalised for an acute exacerbation of COPD. This trial will provide valuable insight into the feasibility of implementing an at-home technology-based feedback intervention for reducing sedentary behaviour into patients existing care. Findings will inform a future large-scale trial acting as an adjuvant to pulmonary rehabilitation.

  18. Statistical analysis of exacerbation rates in COPD: TRISTAN and ISOLDE revisited

    DEFF Research Database (Denmark)

    Keene, O N; Calverley, P M A; Jones, P W;

    2008-01-01

    Various statistical methods have been used to measure the impact of treatment on chronic obstructive pulmonary disease (COPD) exacerbations. Poisson regression has recently been recommended as the appropriate method but the model does not satisfactorily account for variability between patients....... In contrast, use of a negative binomial model, which corresponds to assuming a separate Poisson parameter for each patient, offers a more appealing approach. The present paper reviews analysis methods, with particular focus on the negative binomial model. To illustrate the differences that arise from using...... estimates of exacerbation rates on each treatment arm are higher and the confidence intervals for comparisons between treatments are wider, but the overall conclusions of TRISTAN and ISOLDE regarding reduction of exacerbations remain unchanged. The negative binomial approach appears to provide a better fit...

  19. Montelukast and fluticasone compared with salmeterol and fluticasone in protecting against asthma exacerbation in adults

    DEFF Research Database (Denmark)

    Bjermer, Leif; Bisgaard, Hans; Bousquet, Jean;

    2003-01-01

    patients whose symptoms remained uncontrolled by inhaled corticosteroids were randomised to add montelukast or salmeterol. PARTICIPANTS: Patients (15-72 years; n = 1490) had a clinical history of chronic asthma for > or = 1 year, a baseline forced expiratory volume in one second (FEV1) value 50......OBJECTIVES: To assess the effect of montelukast versus salmeterol added to inhaled fluticasone propionate on asthma exacerbation in patients whose symptoms are inadequately controlled with fluticasone alone. Design and setting A 52 week, two period, double blind, multicentre trial during which......-90% predicted, and a beta agonist improvement of > or = 12% in FEV1. MAIN OUTCOME MEASURES: The primary end point was the percentage of patients with at least one asthma exacerbation. RESULTS: 20.1% of the patients in the group receiving montelukast and fluticasone had an asthma exacerbation compared with 19...

  20. Mesalamine induced symptom exacerbation of ulcerative colitis: Case report and brief discussion

    Institute of Scientific and Technical Information of China (English)

    Maneesh; Kumar; Gupta; Scott; Pollack; John; J; Hutchings

    2010-01-01

    This paper describes a rare case in which the oral ad-ministration of mesalamine resulted in the exacerbation of ulcerative colitis (UC) in a patient who was previously responsive to mesalamine and whose colitis had been in remission for eight years. Mesalamine and other 5-ami-nosalicylic acid compounds are the mainstay of treatment for UC; however up to 8% of patients are unable to take the medications due to intolerance or hypersensitivity reactions. Common drug reactions are fever, nausea, di-arrhea and abdominal pain; however, exacerbation of UC has rarely been reported. This study highlights the impor-tance of ruling out mesalamine as the causative agent in cases of UC exacerbations.

  1. Premenstrual Exacerbation of Life-Threatening Asthma: Effect of Gonadotrophin Releasing Hormone Analogue Therapy

    Directory of Open Access Journals (Sweden)

    Alun L Edwards

    1996-01-01

    Full Text Available Variability in the severity of asthma during various phases of the menstrual cycle has been frequently suspected. However, the hormonal changes that might affect mediators of bronchospasm have yet to be elucidated. The case of a 41-year-old woman suffering from longstanding asthma with life-threatening exacerbations is reported. The patient was treated with buserelin, a gonadotropin releasing hormone (GnRH analogue, which created a temporary chemical menopause and thus permitted diagnosis of a premenstrual exacerbation of asthma and offered insight into potential therapy. GnRH analogues may therefore be of value in assessing women with severe asthma suspected to vary with the menstrual cycle. The addition of estrogens and progestins at the same time as treatment with GnRH analogue may be of value in determining the role of these hormones in the pathogenesis of menstrually related exacerbations of asthma.

  2. Management of pulmonary exacerbations in cystic fibrosis: still an unmet medical need in clinical practice.

    Science.gov (United States)

    Justicia, José Luis; Solé, Amparo; Quintana-Gallego, Esther; Gartner, Silvia; de Gracia, Javier; Prados, Concepción; Máiz, Luis

    2015-04-01

    Pulmonary exacerbation (PEx) is a hallmark of cystic fibrosis. Although several criteria have been proposed for the definition of PEx, no consensus has yet been reached. Very often, many PEx cases go unreported. A standardized and validated definition is needed to reduce variability in clinical practice. The pathophysiology of recurrent episodes remains unclear, and both onset and risk are multifactorial. PEx leads to increased healthcare costs, impaired quality of life and a cycle in which PEx causes loss of lung function, which predisposes to further episodes. The number of episodes affects survival. Although early diagnosis and aggressive treatment are highly recommended, measures to prevent the emergence of new PEx are even more important. In particular, inhaled antibiotics administered under new treatment schedules could play a key role in preventing exacerbations and thus delay decline in lung function and reduce mortality. The primary objective is zero exacerbations. PMID:25692532

  3. Aspirin-Exacerbated Diseases: Advances in Asthma with Nasal Polyposis, Urticaria, Angioedema, and Anaphylaxis.

    Science.gov (United States)

    Stevens, Whitney; Buchheit, Kathleen; Cahill, Katherine N

    2015-12-01

    Aspirin-exacerbated diseases are important examples of drug hypersensitivities and include aspirin-exacerbated respiratory disease (AERD), aspirin- or non-steroidal anti-inflammatory drug (NSAID)-induced urticaria/angioedema, and aspirin- or NSAID-induced anaphylaxis. While each disease subtype may be distinguished by unique clinical features, the underlying mechanisms that contribute to these phenotypes are not fully understood. However, the inhibition of the cyclooxygenase-1 enzyme is thought to play a significant role. Additionally, eosinophils, mast cells, and their products, prostaglandins and leukotrienes, have been identified in the pathogenesis of AERD. Current diagnostic and treatment strategies for aspirin-exacerbated diseases remain limited, and continued research focusing on each of the unique hypersensitivity reactions to aspirin is essential. This will not only advance the understanding of these disease processes, but also lead to the subsequent development of novel therapeutics that patients who suffer from aspirin-induced reactions desperately need. PMID:26475526

  4. A study of air pollutants and acute asthma exacerbations in urban areas: status report

    International Nuclear Information System (INIS)

    Details of a study to investigate the possible roles of a variety of hazardous air pollutants on asthma exacerbations at ambient air concentrations. - A study to try to better understand the interactions between various air contaminants and acute asthma exacerbations is described. The study evaluates temporal associations between a panel of air contaminants and acute asthmatic exacerbations as measured by emergency room visits for asthma in communities in the Bronx and Manhattan in New York City (NYC). In addition, ambient levels of various air pollutants in two NYC communities are being compared. Almost 2 years of daily data have been collected for most of the air contaminants to be investigated. The air contaminants measured include gaseous compounds (ozone, sulfur dioxide, nitrogen oxides, aldehydes, nitrous acid, nitric acid, hydrochloric acid and ammonia), particulate matter components (metals, elemental and organic carbon, sulfate, hydrogen ion, pollen, mold spores and particle mass and number)

  5. ORGANIZATION AND STRUCTURE OF ACTIVITIES IN THE GROUP OF CHILDREN WITH MODERATE MENTAL UNDERDEVELOPMENT FROM 3 TO 6 YEARS OF AGE AND IN THE EARLY DIAGNOSIS CONSULTING-ROOM OF THE DAMAGED CHILDREN’S DAY NURSERY OF PAZARDJIK-BUGARIJA

    Directory of Open Access Journals (Sweden)

    Ilijana MALINOVA

    1997-12-01

    Full Text Available The damaged children’s day nursery of Pazardjik-Bugarija is the result of an initiative taken on, in order to be ensured the necessary conditions for care of damaged children from the region’s area, from 3 to 18 years of age. In the nursery, a consulting room was established for early diagnosis children under risk , from o to 3 years of age.The children at the nursery are divided in four comparatively independent groups, according to their age and degree of damage. Without having the ambition to replace the families, the groups form a kind of “home” with permanent order : a dinning room, a comfortable bathroom, a small kitchen, a living room and a resting room.The adults which are working in teams with the groups, have set themselves the task of education, re-education, or training-according to the abilities of every child-with maximum safety.The organization of assuming responsibility for the children from 3 to 7 years of age begins with making individual plans for every child, which plans are being updated monthly by the whole team that is working with the child concerned ( psychologist, defectologist, supervisor, speech therapist and rehabilitation therapist.The individual plans conforms with the general plan of the group.The education, therapy and training are given to the children trough:A. Education· general education;· specific education;· socialization;· physical activities and leisure time; B. Re-education and Therapy· on psychotherapeutic level;· psychomotor re-education;· re-education of speech;· kinesitherapy;· medical supervision;C. Specialized pedagogical activities used at the nursery, in the group of children with moderate mental underdevelopment, from 3 to 7 years of age

  6. Aspirin treatment exacerbates oral infections by Trypanosoma cruzi.

    Science.gov (United States)

    Cossentini, Luana Aparecida; Da Silva, Rosiane Valeriano; Yamada-Ogatta, Sueli Fumie; Yamauchi, Lucy Megumi; De Almeida Araújo, Eduardo José; Pinge-Filho, Phileno

    2016-05-01

    Oral transmission of the protozoan parasite Trypanosoma cruzi, the etiological agent of Chagas disease, has been documented in Latin American countries. The reported cases of infection were due to the ingestion of contaminated fresh fruit, juices, or sugar cane juice. There have been few studies on the physiopathology of the disease in oral transmission cases. Gastritis is a common ailment that can be caused by poor dietary habits, intake of alcohol or other gastric irritants, bacterial infection, or by the widespread use of non-steroidal anti-inflammatory drugs (NSAIDs). This study investigated in a mouse model whether gastric mucosal injury, induced by aspirin, would affect the course of disease in animals infected with T. cruzi by the oral route. The CL14 and G strains of T. cruzi, both of low infectivity, were used. To this end, groups of BALB/c mice were treated during 5 days with aspirin (100 mg kg(-1)) before oral infection with T. cruzi metacyclic forms (4 × 10(5) or 5 × 10(7) parasites/mouse). Histological analysis and determination of nitric oxide and TNF-α were performed in gastric samples obtained 5 days after infection. Parasitemia was monitored from the thirteenth day after infection. The results indicate that aspirin treatment of mice injured their gastric mucosa and facilitated invasion by both CL14 and G strains of T. cruzi. Strain CL14 caused more severe infection compared to the G strain, as larger numbers of amastigote nests were found in the stomach and parasitemia levels were higher. Our study is novel in that it shows that gastric mucosal damage caused by aspirin, a commonly used NSAID, facilitates T. cruzi infection by the oral route. PMID:26826555

  7. Efficacy and Tolerability of Eight Antimicrobial Regimens in the Outpatient Treatment of Exacerbations of Chronic Obstructive Pulmonary Disease

    OpenAIRE

    Jordan Minov; Jovanka Karadzinska-Bislimovska; Tatjana Petrova; Kristin Vasilevska; Sasho Stoleski; Dragan Mijakoski; Snezhana Risteska-Kuc

    2014-01-01

    BACKGROUND: Bacterial infections are considered as the most important cause of exacerbations in patients with chronic obstructive pulmonary disease. AIM: To compare the efficacy and tolerability of eight antibiotics empirically administered for outpatient treatment of exacerbations of COPD. METHODS: We performed an observational study including 343 COPD patients with probable bacterial exacerbation (Group A and Group B COPD patients) managed in an outpatient setting. Eight antibiotic ...

  8. Telomeres and reproductive aging.

    Science.gov (United States)

    Keefe, David L; Liu, Lin

    2009-01-01

    Infertility, miscarriage and aneuploid offspring increase with age in women, and meiotic dysfunction underlies reproductive aging. How aging disrupts meiotic function in women remains unclear, but as women increasingly delay having children, solving this problem becomes an urgent priority. Telomeres consist of a (TTAGGG)(n) repeated sequence and associated proteins at chromosome ends, mediate aging in mitotic cells and may also mediate aging during meiosis. Telomeres shorten both during DNA replication and from the response to oxidative DNA damage. Oocytes do not divide in adult mammals, but their precursors do replicate during fetal oogenesis; eggs ovulated from older females have traversed more mitotic cell cycles before entering meiosis during fetal oogenesis than eggs ovulated from younger females. Telomeres also would be expected to shorten from inefficient DNA repair of oxidative damage, because the interval between fetal oogenesis and ovulation is exceptionally prolonged in women. We have tested the hypothesis that telomere shortening disrupts meiosis by shortening telomeres experimentally in mice, which normally do not exhibit age-related meiotic dysfunction. Interestingly, mouse telomeres are much longer than human telomeres, but genetic or pharmacological shortening of mouse telomeres recapitulates in mice the human reproductive aging phenotype as the mouse telomeres reach the length of telomeres from older women. These observations led us to propose a telomere theory of reproductive aging. Moreover, chronological oxidative stress increases with reproductive aging, leading to DNA damage preferentially at (TTAGGG)(n) repeats. Finally, if telomeres shorten with aging, how do they reset across generations? Telomerase could not play a significant role in telomere elongation during early development, because this enzyme is not active until the blastocyst stage, well after the stage when telomere elongation takes place. Rather, telomeres lengthen during the

  9. [Eosinophil cationic protein in children with allergic diseases of the respiratory tract in exacerbation and remission of symptoms].

    Science.gov (United States)

    Marciniak, D; Tomaszewicz-Fryca, J; Płusa, T; Chciałowski, A

    1998-02-01

    The role of eosinophil cationic protein (ECP) in allergic inflammatory reaction has been documented in experimental and clinical studies, but a clinical usefulness is still discussed. In the study serum level of ECP has been evaluated in children with allergic diseases of the respiratory system in exacerbation and remission of symptoms for purpose of monitoring of disease course. In 111 children aged 12.0 +/- 3.3 yrs with atopic bronchial asthma and/ or allergic rhinits ECP serum concentrations have been determined in following groups: children with grass pollen hypersensitivity (group P, 17 female and 41 male), children with hypersensitivity to D. pteronyssinus and D. farinae (group D, 16 female and 37 male) and controls without allergic hypersensitivity with negative prick skin tests (19 children, 11 female and 5 male). All children have been qualified to immunotherapy with pollen or mite allergens (Allergovit or Novo-Helisen, Nexter, Allergopharma) and ECP evaluation was performed before, during and after therapy. Serum ECP and IgE levels have been determined with CAP-system (Pharmacia) and obtained results related to clinical symptoms. In all analyzed children serum total IgE has been significantly increased in relation to controls. Serum ECP levels have been increased during clinical exacerbation of symptoms in observed children and parallel with clinical score of symptoms, especially during pollen season. Authors conclude that a degree of increase of serum ECP level is parallel with clinical score of symptoms, especially during highest exposition to pollen allergens. Observed changes of serum ECP levels during immunotherapy suggest the close relationship with allergic inflammatory reaction and indicate clinical usefulness for monitoring of this process. PMID:9591438

  10. Expiratory flow limitation relates to symptoms during COPD exacerbations requiring hospital admission

    Science.gov (United States)

    Jetmalani, Kanika; Timmins, Sophie; Brown, Nathan J; Diba, Chantale; Berend, Norbert; Salome, Cheryl M; Wen, Fu-Qiang; Chen, Peng; King, Gregory G; Farah, Claude S

    2015-01-01

    Background Expiratory flow limitation (EFL) is seen in some patients presenting with a COPD exacerbation; however, it is unclear how EFL relates to the clinical features of the exacerbation. We hypothesized that EFL when present contributes to symptoms and duration of recovery during a COPD exacerbation. Our aim was to compare changes in EFL with symptoms in subjects with and without flow-limited breathing admitted for a COPD exacerbation. Subjects and methods A total of 29 subjects with COPD were recruited within 48 hours of admission to West China Hospital for an acute exacerbation. Daily measurements of post-bronchodilator spirometry, resistance, and reactance using the forced oscillation technique and symptom (Borg) scores until discharge were made. Flow-limited breathing was defined as the difference between inspiratory and expiratory respiratory system reactance (EFL index) greater than 2.8 cmH2O·s·L−1. The physiological predictors of symptoms during recovery were determined by mixed-effect analysis. Results Nine subjects (31%) had flow-limited breathing on admission despite similar spirometry compared to subjects without flow-limited breathing. Spirometry and resistance measures did not change between enrolment and discharge. EFL index values improved in subjects with flow-limited breathing on admission, with resolution in four patients. In subjects with flow-limited breathing on admission, symptoms were related to inspiratory resistance and EFL index values. In subjects without flow-limited breathing, symptoms related to forced expiratory volume in 1 second/forced vital capacity. In the whole cohort, EFL index values at admission was related to duration of stay (Rs=0.4, P=0.03). Conclusion The presence of flow-limited breathing as well as abnormal respiratory system mechanics contribute independently to symptoms during COPD exacerbations. PMID:25999709

  11. Physical activity and exercise capacity in patients with moderate COPD exacerbations.

    Science.gov (United States)

    Alahmari, Ayedh D; Kowlessar, Beverly S; Patel, Anant R C; Mackay, Alex J; Allinson, James P; Wedzicha, Jadwiga A; Donaldson, Gavin C

    2016-08-01

    Little is known about changes in physical activity during moderate (out-patient managed) exacerbations.6-min walking distance (6MWD) was measured during 50 exacerbations when the patients were stable, and at 3 and 7 days post-exacerbation presentation. At similar time points, quadriceps maximum voluntary contraction (QMVC) was measured during 47 different exacerbations. Physical activity (SenseWear; Bodymedia Inc., Pittsburgh, PA, USA) was recorded over 2 consecutive-week periods post-presentation.6MWD fell from a median 422 m when stable to 373 m on day 3 (p=0.001). Similarly, QMVC fell from 32.6 versus 29.7 kg (p=0.026). Falls in 6MWD were associated with a rise in C-reactive protein (r= -0.364; p=0.041) and increased Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) (r= -0.44; p=0.013). Light physical activity was 2.18 h·day(-1) during the first week post-exacerbation and was less over week 2 (1.98 h·day(-1); p=0.009). Patients who had attended pulmonary rehabilitation had smaller changes in 6MWD than those who had not attended (-35.0 versus -114.9 m; p=0.013). Falls in physical activity were correlated with higher depression scores (rho= -0.51; p=0.006).These findings indicate that exercise capacity and muscle strength fall at exacerbation in chronic obstructive pulmonary disease patients who are treated at home and are free to maintain normal activity. PMID:27126688

  12. Domiciliary pulse-oximetry at exacerbation of chronic obstructive pulmonary disease: prospective pilot study

    Directory of Open Access Journals (Sweden)

    Goldring James JP

    2010-10-01

    Full Text Available Abstract Background The ability to objectively differentiate exacerbations of chronic obstructive pulmonary disease (COPD from day-to-day symptom variations would be an important development in clinical practice and research. We assessed the ability of domiciliary pulse oximetry to achieve this. Methods 40 patients with moderate-severe COPD collected daily data on changes in symptoms, heart-rate (HR, oxygen saturation (SpO2 and peak-expiratory flow (PEF over a total of 2705 days. 31 patients had data suitable for baseline analysis, and 13 patients experienced an exacerbation. Data were expressed as multiples of the standard deviation (SD observed from each patient when stable. Results In stable COPD, the SD for HR, SpO2 and PEF were approximately 5 min-1, 1% and 10l min-1. There were detectable changes in all three variables just prior to exacerbation onset, greatest 2-3 days following symptom onset. A composite Oximetry Score (mean magnitude of SpO2 fall and HR rise distinguished exacerbation onset from symptom variation (area under receiver-operating characteristic curve, AUC = 0.832, 95%CI 0.735-0.929, p = 0.003. In the presence of symptoms, a change in Score of ≥1 (average of ≥1SD change in both HR and SpO2 was 71% sensitive and 74% specific for exacerbation onset. Conclusion We have defined normal variation of pulse oximetry variables in a small sample of patients with COPD. A composite HR and SpO2 score distinguished exacerbation onset from symptom variation, potentially facilitating prompt therapy and providing validation of such events in clinical trials.

  13. Outcomes of Noninvasive Ventilation for Acute Exacerbations of Chronic Obstructive Pulmonary Disease in the United States, 1998–2008

    OpenAIRE

    Chandra, Divay; Stamm, Jason A.; Taylor, Brian; Ramos, Rose Mary; Satterwhite, Lewis; Krishnan, Jerry A.; Mannino, David; Sciurba, Frank C.; Holguín, Fernando

    2012-01-01

    Rationale: The patterns and outcomes of noninvasive, positive-pressure ventilation (NIPPV) use in patients hospitalized for acute exacerbations of chronic obstructive pulmonary disease (COPD) nationwide are unknown.

  14. Viruses and bacteria in acute asthma exacerbations - A GA(2) LEN-DARE* systematic review

    DEFF Research Database (Denmark)

    Papadopoulos, N G; Christodoulou, I; Rohde, G;

    2011-01-01

    accurate and sensitive methodologies. This systematic review summarizes current knowledge and developments in infection epidemiology of acute asthma in children and adults, describing the known impact for each individual agent and highlighting knowledge gaps. Among infectious agents, human rhinoviruses are...... the most prevalent in regard to asthma exacerbations. The newly identified type-C rhinoviruses may prove to be particularly relevant. Respiratory syncytial virus and metapneumovirus are important in infants, while influenza viruses seem to induce severe exacerbations mostly in adults. Other agents are...

  15. Low Root Zone Temperature Exacerbates the Ion Imbalance and Photosynthesis Inhibition and Induces Antioxidant Responses in Tomato Plants Under Salinity

    Institute of Scientific and Technical Information of China (English)

    HE Yong; YANG Jing; ZHU Biao; ZHU Zhu-jun

    2014-01-01

    The combined effects of salinity with low root zone temperature (RZT) on plant growth and photosynthesis were studied in tomato (Solanum lycopersicum) plants. The plants were exposed to two different root zone temperatures (28/20°C, 12/8°C, day/night temperature) in combination with two NaCl levels (0 and 100 mmol L-1). After 2 wk of treatment, K+and Na+ concentration, leaf photosynthetic gas exchange, chlorophyll lfuorescence and leaf antioxidant enzyme activities were measured. Salinity signiifcantly decreased plant biomass, net photosynthesis rate, actual quantum yield of photosynthesis and concentration of K+, but remarkably increased the concentration of Na+. These effects were more pronounced when the salinity treatments were combined with the treatment of low RZT conditions. Either salinity or low RZT individually did not affect maximal efifciency of PSII photochemistry (Fv/Fm), while a combination of these two stresses decreased Fv/Fm considerably, indicating that the photo-damage occurred under such conditions. Non-photochemical quenching was increased by salt stress in accompany with the enhancement of the de-epoxidation state of the xanthophyll cycle, in contrast, this was not the case with low RZT applied individually. Salinity stress individually increased the activities of SOD, APX, GPOD and GR, and decreased the activities of DHAR. Due to the interactive effects of salinity with low RZT, these ifve enzyme activities increased sharply in the combined stressed plants. These results indicate that low RZT exacerbates the ion imbalance, PSII damage and photosynthesis inhibition in tomato plants under salinity. In response to the oxidative stress under salinity in combination with low RZT, the activities of antioxidant enzymes SOD, APX, GPOD, DHAR and GR were clearly enhanced in tomato plants.

  16. Expression of suppressor of cytokine signaling 1 (SOCS1 impairs viral clearance and exacerbates lung injury during influenza infection.

    Directory of Open Access Journals (Sweden)

    Keer Sun

    2014-12-01

    Full Text Available Suppressor of cytokine signaling (SOCS proteins are inducible feedback inhibitors of cytokine signaling. SOCS1-/- mice die within three weeks postnatally due to IFN-γ-induced hyperinflammation. Since it is well established that IFN-γ is dispensable for protection against influenza infection, we generated SOCS1-/-IFN-γ-/- mice to determine whether SOCS1 regulates antiviral immunity in vivo. Here we show that SOCS1-/-IFN-γ-/- mice exhibited significantly enhanced resistance to influenza infection, as evidenced by improved viral clearance, attenuated acute lung damage, and consequently increased survival rates compared to either IFN-γ-/- or WT animals. Enhanced viral clearance in SOCS1-/-IFN-γ-/- mice coincided with a rapid onset of adaptive immune responses during acute infection, while their reduced lung injury was associated with decreased inflammatory cell infiltration at the resolution phase of infection. We further determined the contribution of SOCS1-deficient T cells to antiviral immunity. Anti-CD4 antibody treatment of SOCS1-/-IFN-γ-/- mice had no significant effect on their enhanced resistance to influenza infection, while CD8+ splenocytes from SOCS1-/-IFN-γ-/- mice were sufficient to rescue RAG1-/- animals from an otherwise lethal infection. Surprisingly, despite their markedly reduced viral burdens, RAG1-/- mice reconstituted with SOCS1-/-IFN-γ-/- adaptive immune cells failed to ameliorate influenza-induced lung injury. In conclusion, in the absence of IFN-γ, the cytoplasmic protein SOCS1 not only inhibits adaptive antiviral immune responses but also exacerbates inflammatory lung damage. Importantly, these detrimental effects of SOCS1 are conveyed through discrete cell populations. Specifically, while SOCS1 expression in adaptive immune cells is sufficient to inhibit antiviral immunity, SOCS1 in innate/stromal cells is responsible for aggravated lung injury.

  17. Cyclooxygenase- and Lipoxygenase-Mediated DNA Damage

    OpenAIRE

    Speed, N; Blair, I. A.

    2011-01-01

    Cancer is a disease of aging and so with the increasing age of the US population, the incidence of cancer is also increasing. Furthermore the global burden of cancer continues to increase largely because of aging and growth of the world population together with increasing smoking rates in economically developing countries. Tumor formation is critically dependent upon two processes – initiation and progression. The initiation step is mediated by DNA damage, which causes activating mutations in...

  18. Damaging effects of visible light. Comprehensive progress report

    Energy Technology Data Exchange (ETDEWEB)

    None

    1981-01-01

    Research progress is reported on studies of retinal light damage. A myriad of variables effect the production of light damage. These include age, prior light history, body temperature, vitamin A status, intensity, wavelength and duration of light. The intensity-duration function and the age function have been studied in detail in rats. Studies have been begun on the wavelength variable. (ACR)

  19. [Vitamin E in the aged].

    Science.gov (United States)

    Pentimone, F; del Corso, L; Laghi, G

    1994-06-01

    Aging is a multifactorial process still incompletely known. The role of oxidative damage to cell membranes, as an important phase of the process, is underlined by the recent literature. We emphasize the value of vitamin E as an antioxidant agent supplied by suitable diets in middle age and by cheap tablets in the aged. PMID:8001337

  20. Diabetes and nerve damage

    Science.gov (United States)

    Nerve damage that occurs in people with diabetes is called diabetic neuropathy. This condition is a complicaiton ... In people with diabetes, the body's nerves can be damaged by ... sugar level . This condition is more likely when the blood sugar ...

  1. Femoral nerve damage (image)

    Science.gov (United States)

    The femoral nerve is located in the leg and supplies the muscles that assist help straighten the leg. It supplies sensation ... leg. One risk of damage to the femoral nerve is pelvic fracture. Symptoms of femoral nerve damage ...

  2. Employer's liability for damage

    OpenAIRE

    Baštýřová, Markéta

    2010-01-01

    The purpose of this bachelor thesis is to analyse and clarify in detail the issue of liability for damage in Labour law with focus on liability for damage of employer. At first the thesis defines conception of liability and liability in Labour law in general. The thesis also deals with characteristic features, functions and prevention of liability for damage in Labour law as well. The main part is devoted to liability for damage of employer with regards to judicial decision. It explains gener...

  3. Bacteriology in acute exacerbation of chronic obstructive pulmonary disease in patients admitted to hospital

    DEFF Research Database (Denmark)

    Larsen, Mette V; Janner, Julie H; Nielsen, Susanne D; Friis-Møller, Alice; Ringbaek, Thomas; Lange, Peter

    2009-01-01

    We investigated the bacterial flora and antimicrobial sensitivity in sputum from patients admitted to hospital with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in order to recommend the best empirical treatment for these patients. The survey was a retrospective study of a...... AECOPD we recommend either cefuroxime for intravenous treatment or amoxicillin-clavulanate for oral treatment....

  4. Treatment of patients with COPD and recurrent exacerbations: the role of infection and inflammation

    Science.gov (United States)

    Santos, Salud; Marin, Alicia; Serra-Batlles, Joan; de la Rosa, David; Solanes, Ingrid; Pomares, Xavier; López-Sánchez, Marta; Muñoz-Esquerre, Mariana; Miravitlles, Marc

    2016-01-01

    Exacerbations of COPD represent an important medical and health care problem. Certain susceptible patients suffer recurrent exacerbations and as a consequence have a poorer prognosis. The effects of bronchial infection, either acute or chronic, and of the inflammation characteristic of the disease itself raise the question of the possible role of antibiotics and anti-inflammatory agents in modulating the course of the disease. However, clinical guidelines base their recommendations on clinical trials that usually exclude more severe patients and patients with more comorbidities, and thus often fail to reflect the reality of clinicians attending more severe patients. In order to discuss aspects of clinical practice of relevance to pulmonologists in the treatment and prevention of recurrent exacerbations in patients with severe COPD, a panel discussion was organized involving expert pulmonologists who devote most of their professional activity to day hospital care. This article summarizes the scientific evidence currently available and the debate generated in relation to the following aspects: bacterial and viral infections, chronic bronchial infection and its treatment with cyclic oral or inhaled antibiotics, inflammatory mechanisms and their treatment, and the role of computerized tomography as a diagnostic tool in patients with severe COPD and frequent exacerbations. PMID:27042040

  5. Acute exacerbations of chronic obstructive pulmonary disease provide a unique opportunity to take care of patients

    Directory of Open Access Journals (Sweden)

    Bianca Beghé

    2013-04-01

    Full Text Available Exacerbation of chronic obstructive pulmonary disease (ECOPD identifies the acute phase of COPD. The COPD patient is often frail and elderly with concomitant chronic diseases. This requires the physician not only looks at specific symptoms or organs, but to consider the patient in all his or her complexity.

  6. A telecare programme for self-management of COPD exacerbations and promotion of an active lifestyle

    NARCIS (Netherlands)

    Tabak, Monique; Brusse-Keizer, Marjolein; Ommeren, Clara; Kotte, Hayke; Weltevreden, Paul; Hermens, Hermie; Vollenbroek-Hutten, Miriam

    2013-01-01

    Objective: The Condition Coach (CoCo) is a technology-supported care programme for self-management of COPD exacerbations and for promotion of an active lifestyle. The objective is to investigate the added value of the telecare programme in terms of clinical changes compared to usual care, and in add

  7. A collagen IV matrikine inhibits neutrophil recruitment in a mouse model of asthma exacerbation

    NARCIS (Netherlands)

    Weckmann, M.; Nissen, G.; Lundig, L.; Burgess, J.K.; Holst, O.; Wegmann, M.; Kopp, M.V.

    2015-01-01

    Background: Increased neutrophilic infiltration of the airways is a key feature of acute asthma exacerbation, which may lead to prolonged hospital admissions and an enhanced rate of decline of lung function. The increase in asthma severity in this subpobulation of patients is thought to be partially

  8. Reliever salbutamol use as a measure of exacerbation risk in chronic obstructive pulmonary disease

    NARCIS (Netherlands)

    Jenkins, Christine R.; Postma, Dirkje S.; Anzueto, Antonio R.; Make, Barry J.; Peterson, Stefan; Eriksson, Goran; Calverley, Peter M.

    2015-01-01

    Background: Debate exists regarding which endpoints most sensitively reflect day-to-day variation in chronic obstructive pulmonary disease (COPD) symptoms and are most useful in clinical practice to predict COPD exacerbations. We hypothesized that short-acting beta(2)-agonist (SABA) reliever use wou

  9. Aggression among Children with ADHD, Anxiety, or Co-Occurring Symptoms: Competing Exacerbation and Attenuation Hypotheses

    Science.gov (United States)

    Becker, Stephen P.; Luebbe, Aaron M.; Stoppelbein, Laura; Greening, Leilani; Fite, Paula J.

    2012-01-01

    Competing hypotheses for explaining the role of anxiety in the relation between attention-deficit/hyperactivity disorder (ADHD) symptoms and childhood aggression were evaluated. Two studies tested whether anxiety exacerbated, attenuated, or had no effect on the relation between ADHD and aggression subtypes among psychiatrically hospitalized…

  10. Trauma-focused treatment in PTSD patients with psychosis: Symptom exacerbation, adverse events, and revictimization

    NARCIS (Netherlands)

    Berg, D.P.G. van den; Bont, P.A.J.M. de; Vleugel, B.M. van der; Roos, C.J.A.M. de; Jongh, A. de; Minnen, A. van; Gaag, M. van der

    2016-01-01

    Objectives: Most clinicians refrain from trauma treatment for patients with psychosis because they fear symptom exacerbation and relapse. This study examined the negative side effects of trauma-focused (TF) treatment in patients with psychosis and posttraumatic stress disorder (PTSD). Methods: Analy

  11. Bronchodilator response following methacholine-induced bronchoconstriction predicts acute asthma exacerbations.

    Science.gov (United States)

    Park, Heung-Woo; Song, Woo-Jung; Chang, Yoon-Suk; Cho, Sang-Heon; Datta, Soma; Weiss, Scott T; Tantisira, Kelan G

    2016-07-01

    Methacholine bronchial provocation test provides the concentration of methacholine causing a 20% decrease in forced expiratory volume in 1 s (FEV1) from baseline (PC20). The dose-response slope (DRS), and other continuous indices of responsiveness (CIR; the percentage decline from the post-diluent baseline FEV1 after the last dose of methacholine), and per cent recovery index (PRI; the percentage increase from the maximally reduced FEV1 after bronchodilator inhalation) are alternative measures. The clinical relevance of these indices in predicting acute asthma exacerbations has not been fully evaluated.In two prospective cohorts of childhood and elderly asthmatics, baseline PC20, DRS, CIR and PRI were measured and evaluated as predictors of acute asthma exacerbations.We found that PRI was significantly related to the presence of asthma exacerbations during the first year of follow-up in both cohorts of childhood (p=0.025) and elderly asthmatics (p=0.003). In addition, PRI showed a significant association with the total number of steroid bursts during 4.3 years of follow-up in the cohort of childhood asthmatics (p=0.04).We demonstrated that PRI, an index of reversibility following methacholine-induced bronchoconstriction, was a good clinical predictor of acute exacerbations of asthma in both childhood and elderly asthmatics. PMID:27076579

  12. Prompt initiation of maintenance treatment following a COPD exacerbation: outcomes in a large insured population

    Directory of Open Access Journals (Sweden)

    Coutinho AD

    2016-06-01

    Full Text Available Anna D Coutinho,1 Tasneem Lokhandwala,1 Robert L Boggs,2 Anand A Dalal,2 Pamela B Landsman-Blumberg,1 Julie Priest,2 David A Stempel3 1Real World Evidence, Xcenda LLC, Palm Harbor, FL, 2US Health Outcomes, GlaxoSmithKline, Research Triangle Park, NC, 3US Medical Affairs, GlaxoSmithKline, Research Triangle Park, NC, USA Background: The aim of this study was to extend previous findings and determine the value of prompt initiation of maintenance treatment (MT following COPD exacerbations requiring hospitalization or an emergency department (ED visit.Patients and methods: Administrative claims data (collected between January 1, 2009 and June 30, 2012 from an employer-sponsored commercially insured population were retrospectively used to identify patients with a COPD exacerbation resulting in hospitalization or an ED visit. Patients initiating approved MT for COPD within 30 days of discharge/diagnosis (prompt were compared with those initiating MT within 31–180 days (delayed. COPD-related total, medical, and prescription drug costs during a 1-year follow-up period were evaluated using semilog ordinary least square regressions, controlling for baseline characteristics plus COPD-related costs from the previous year. The odds and number of subsequent COPD-related exacerbations during the follow-up were compared between the prompt and delayed cohorts using logistic regression and zero-inflated negative binomial models, respectively. Results: A total of 6,521 patients with a COPD-related hospitalization or an ED visit were included, of whom 4,555 received prompt MT and 1,966 received delayed MT. Adjusted COPD-related total and medical costs were significantly lower for the prompt MT than the delayed MT cohorts (US$3,931 vs US$4,857 and US$2,327 vs US$3,087, respectively; both P<0.010, as were COPD-related prescription costs (US$1,526 vs US$1,683, P<0.010 during the 1-year follow-up period. Patients receiving delayed MT were 68% more likely to have a

  13. Expiratory flow limitation relates to symptoms during COPD exacerbations requiring hospital admission

    Directory of Open Access Journals (Sweden)

    Jetmalani K

    2015-05-01

    Full Text Available Kanika Jetmalani,1,2 Sophie Timmins,1,3,4 Nathan J Brown,1,4 Chantale Diba,1,4 Norbert Berend,1,4,5 Cheryl M Salome,1,2,4 Fu-Qiang Wen,6 Peng Chen,6 Gregory G King,1-4 Claude S Farah1,2,7 1Woolcock Institute of Medical Research, 2Sydney Medical School, University of Sydney, 3Department of Respiratory Medicine, Royal North Shore Hospital, 4Cooperative Research Centre for Asthma and Airways, 5Department of Respiratory Research, George Institute of Global Health, Sydney, NSW, Australia; 6Department of Medicine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, People’s Republic of China; 7Department of Respiratory Medicine, Concord Hospital, Sydney, NSW, Australia Background: Expiratory flow limitation (EFL is seen in some patients presenting with a COPD exacerbation; however, it is unclear how EFL relates to the clinical features of the exacerbation. We hypothesized that EFL when present contributes to symptoms and duration of recovery during a COPD exacerbation. Our aim was to compare changes in EFL with symptoms in subjects with and without flow-limited breathing admitted for a COPD exacerbation.Subjects and methods: A total of 29 subjects with COPD were recruited within 48 hours of admission to West China Hospital for an acute exacerbation. Daily measurements of postbronchodilator spirometry, resistance, and reactance using the forced oscillation technique and symptom (Borg scores until discharge were made. Flow-limited breathing was defined as the difference between inspiratory and expiratory respiratory system reactance (EFL index greater than 2.8 cmH2O·s·L-1. The physiological predictors of symptoms during recovery were determined by mixed-effect analysis.Results: Nine subjects (31% had flow-limited breathing on admission despite similar spirometry compared to subjects without flow-limited breathing. Spirometry and resistance measures did not change between enrolment and discharge. EFL index values improved

  14. A novel study design for antibiotic trials in acute exacerbations of COPD: MAESTRAL methodology

    Directory of Open Access Journals (Sweden)

    Wilson R

    2011-06-01

    Full Text Available Robert Wilson1, Antonio Anzueto2, Marc Miravitlles3, Pierre Arvis4, Geneviève Faragó5, Daniel Haverstock6, Mila Trajanovic5, Sanjay Sethi71Host Defence Unit, Royal Brompton Hospital, London, England, UK; 2University of Texas Health Science Center at San Antonio, South Texas Veterans HealthCare System, San Antonio, TX, USA; 3Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS, Ciber de Enfermedades Respiratorias (CIBERES, Hospital Clinic, Barcelona, Spain; 4Bayer HealthCare, Loos, France; 5Bayer Inc, Toronto, ON, Canada; 6Bayer HealthCare Pharmaceuticals, Montville, NJ, USA; 7Division of Pulmonary, Critical Care and Sleep Medicine, University at Buffalo, State University of New York, Buffalo, NY, USAAbstract: Antibiotics, along with oral corticosteroids, are standard treatments for acute exacerbations of chronic obstructive pulmonary disease (AECOPD. The ultimate aims of treatment are to minimize the impact of the current exacerbation, and by ensuring complete resolution, reduce the risk of relapse. In the absence of superiority studies of antibiotics in AECOPD, evidence of the relative efficacy of different drugs is lacking, and so it is difficult for physicians to select the most effective antibiotic. This paper describes the protocol and rationale for MAESTRAL (moxifloxacin in AECBs [acute exacerbation of chronic bronchitis] trial; www.clinicaltrials.gov: NCT00656747, one of the first antibiotic comparator trials designed to show superiority of one antibiotic over another in AECOPD. It is a prospective, multinational, multicenter, randomized, double-blind controlled study of moxifloxacin (400 mg PO [per os] once daily for 5 days vs amoxicillin/clavulanic acid (875/125 mg PO twice daily for 7 days in outpatients with COPD and chronic bronchitis suffering from an exacerbation. MAESTRAL uses an innovative primary endpoint of clinical failure: the requirement for additional or alternate treatment for the exacerbation at 8 weeks

  15. Over-expression of human endosulfatase-1 exacerbates cadmium-induced injury to transformed human lung cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Huiying [Department of Molecular Biomedical Sciences, Center for Comparative Molecular Translational Research, College of Veterinary Medicine, NC State University, Raleigh, NC 27607 (United States); Department of Environmental and Molecular Toxicology, College of Agriculture and Life Sciences, NC State University, Raleigh, NC 27695 (United States); Newman, Donna R. [Department of Molecular Biomedical Sciences, Center for Comparative Molecular Translational Research, College of Veterinary Medicine, NC State University, Raleigh, NC 27607 (United States); Bonner, James C. [Department of Environmental and Molecular Toxicology, College of Agriculture and Life Sciences, NC State University, Raleigh, NC 27695 (United States); Sannes, Philip L., E-mail: philip_sannes@ncsu.edu [Department of Molecular Biomedical Sciences, Center for Comparative Molecular Translational Research, College of Veterinary Medicine, NC State University, Raleigh, NC 27607 (United States)

    2012-11-15

    Environmental exposure to cadmium is known to cause damage to alveolar epithelial cells of the lung, impair their capacity to repair, and result in permanent structural alterations. Cell surface heparan sulfate proteoglycans (HSPGs) can modulate cell responses to injury through their interactions with soluble effector molecules. These interactions are often sulfate specific, and the removal of sulfate groups from HS side chains could be expected to influence cellular injury, such as that caused by exposure to cadmium. The goal of this study was to define the role 6-O-sulfate plays in cellular responses to cadmium exposure in two pulmonary epithelial cancer cell lines (H292 and A549) and in normal human primary alveolar type II (hAT2) cells. Sulfate levels were modified by transduced transient over-expression of 6-O-endosulfatase (HSulf-1), a membrane-bound enzyme which specifically removes 6-O-sulfate groups from HSPG side chains. Results showed that cadmium decreased cell viability and activated apoptosis pathways at low concentrations in hAT2 cells but not in the cancer cells. HSulf-1 over-expression, on the contrary, decreased cell viability and activated apoptosis pathways in H292 and A549 cells but not in hAT2 cells. When combined with cadmium, HSulf-1 over-expression further decreased cell viability and exacerbated the activation of apoptosis pathways in the transformed cells but did not add to the toxicity in hAT2 cells. The finding that HSulf-1 sensitizes these cancer cells and intensifies the injury induced by cadmium suggests that 6-O-sulfate groups on HSPGs may play important roles in protection against certain environmental toxicants, such as heavy metals. -- Highlights: ► Primary human lung alveolar type 2 (hAT2) cells and H292 and A549 cells were used. ► Cadmium induced apoptosis in hAT2 cells but not in H292 or A549 cells. ► HSulf-1exacerbates apoptosis induced by cadmium in H292 and A549 but not hAT2 cells.

  16. Cefditoren versus levofloxacin in patients with exacerbations of chronic bronchitis: serum inflammatory biomarkers, clinical efficacy, and microbiological eradication

    Directory of Open Access Journals (Sweden)

    Blasi F

    2013-02-01

    reduction of interleukin-6 and KL-6, two key mediators of lung inflammation and epithelial damage.Keywords: cefditoren pivoxil, levofloxacin, serum inflammatory biomarkers, chronic bronchitis, acute exacerbations

  17. Viral Etiology of Chronic Obstructive Pulmonary Disease Exacerbations during the A/H1N1pdm09 Pandemic and Postpandemic Period

    Directory of Open Access Journals (Sweden)

    Ivan Sanz

    2015-01-01

    Full Text Available Viral infections are one of the main causes of acute exacerbations of chronic obstructive pulmonary disease (AE-COPD. Emergence of A/H1N1pdm influenza virus in the 2009 pandemic changed the viral etiology of exacerbations that were reported before the pandemic. The aim of this study was to describe the etiology of respiratory viruses in 195 Spanish patients affected by AE-COPD from the pandemic until the 2011-12 influenza epidemic. During the study period (2009–2012, respiratory viruses were identified in 48.7% of samples, and the proportion of viral detections in AE-COPD was higher in patients aged 30–64 years than ≥65 years. Influenza A viruses were the pathogens most often detected during the pandemic and the following two influenza epidemics in contradistinction to human rhino/enteroviruses that were the main viruses causing AE-COPD before the pandemic. The probability of influenza virus detection was 2.78-fold higher in patients who are 30–64 years old than those ≥65. Most respiratory samples were obtained during the pandemic, but the influenza detection rate was higher during the 2011-12 epidemic. There is a need for more accurate AE-COPD diagnosis, emphasizing the role of respiratory viruses. Furthermore, diagnosis requires increased attention to patient age and the characteristics of each influenza epidemic.

  18. Systemic administration of the chemokine macrophage inflammatory protein 1α exacerbates inflammatory bowel disease in a mouse model

    OpenAIRE

    Pender, S L-F; Chance, V; Whiting, C V; Buckley, M; Edwards, M.; Pettipher, R; MacDonald, T T

    2005-01-01

    Introduction: Exacerbations of inflammatory bowel disease are thought to be related to concurrent infections. As infections are associated with elevated local and serum concentrations of chemokines, we have determined whether systemic administration of the CC chemokine macrophage inflammatory protein 1α (MIP-1α) exacerbates colitis in a mouse model.

  19. A genome-wide association study identifies CDHR3 as a susceptibility locus for early childhood asthma with severe exacerbations

    NARCIS (Netherlands)

    Bonnelykke, Klaus; Sleiman, Patrick; Nielsen, Kasper; Kreiner-Moller, Eskil; Mercader, Josep M.; Belgrave, Danielle; den Dekker, Herman T.; Husby, Anders; Sevelsted, Astrid; Faura Tellez, Grissel; Mortensen, Li Juel; Paternoster, Lavinia; Flaaten, Richard; Molgaard, Anne; Smart, David E.; Thomsen, Philip F.; Rasmussen, Morten A.; Bonas-Guarch, Silvia; Holst, Claus; Nohr, Ellen A.; Yadav, Rachita; March, Michael E.; Blicher, Thomas; Lackie, Peter M.; Jaddoe, Vincent W. V.; Simpson, Angela; Holloway, John W.; Duijts, Liesbeth; Custovic, Adnan; Davies, Donna E.; Torrents, David; Gupta, Ramneek; Hollegaard, Mads V.; Hougaard, David M.; Hakonarson, Hakon; Bisgaard, Hans

    2014-01-01

    Asthma exacerbations are among the most frequent causes of hospitalization during childhood, but the underlying mechanisms are poorly understood. We performed a genome-wide association study of a specific asthma phenotype characterized by recurrent, severe exacerbations occurring between 2 and 6 yea

  20. Effects of age and radiation treatment on function of extrinsic tongue muscles

    International Nuclear Information System (INIS)

    Radiation treatment for head and neck cancer often results in difficulty swallowing. Muscle weakness and fibrosis have been identified clinically as possible etiologies for swallowing problems following radiation. Aging may compound the effects of radiation on swallowing because radiation-induced damage to muscles and other tissues critical for the oropharyngeal swallow is overlaid on a declining sensorimotor system. However, there have been no investigations of the manner in which aging and radiation treatment effects combine to impact tongue muscles, which are critical effectors of the oropharyngeal swallow. Thirty-seven male Fisher 344/Brown Norway rats were divided into four groups; young adults (9 month old), old (32 months old), young radiation (9 months), and old radiation (32 months old). Two fractions of 11 Gy on consecutive days was delivered by external beam radiation to the ventral side of the rat’s body over the anterior portion (20 X 30 mm area) of the anterior digastric muscle. Two-way analysis of variance (ANOVA) was used to examine the effects of age and radiation and their interaction on muscle contractile properties. Post-hoc testing was completed using Fisher’s least significant differences (LSD). Radiation was associated with a significant decrease in tongue force production and reduced speed of tongue muscle contraction. However, radiation treatment did not lead to muscle atrophy and fibrosis formation in the GG muscle. Radiation treatment did not exacerbate atrophic changes observed with aging, or lead to additional fibrosis formation in the GG muscle from that observed in the other groups. The purpose of this research was to determine the effect of radiation on muscles of the tongue and to determine whether aging altered the extent of radiation injury to tongue muscles. Radiation was associated with a significant decrease in tongue force production and reduced speed of tongue muscle contraction, and the reduction in the speed of tongue

  1. Mechanism of exacerbative effect of progesterone on drug-induced liver injury.

    Science.gov (United States)

    Toyoda, Yasuyuki; Endo, Shinya; Tsuneyama, Koichi; Miyashita, Taishi; Yano, Azusa; Fukami, Tatsuki; Nakajima, Miki; Yokoi, Tsuyoshi

    2012-03-01

    Drug-induced liver injury (DILI) is a major safety concern in drug development and clinical drug therapy. However, the underlying mechanism of DILI is little known. It is generally believed that women exhibit worse outcomes from DILI than men. Recently, we found that pretreatment of mice with estradiol attenuated halothane (HAL)-induced liver injury, whereas pretreatment with progesterone exacerbated it in female mice. To investigate the mechanism of sex difference of DILI, we focused on progesterone in this study. We found the exacerbating effect of progesterone in thioacetamide (TA), α-naphthylisothiocyanate, and dicloxacillin-induced liver injury only in female mice. Higher number of myeloperoxidase-positive mononuclear cells infiltrated into the liver and increased levels of Chemokine (C-X-C motif) ligand 1 and 2 (CXCL1 and CXCL2) and intercellular adhesion molecule-1 in the liver were observed. Interestingly, CXCL1 was slightly increased by progesterone pretreatment alone. Progesterone pretreatment increased the extracellular signal-regulated kinase (ERK) phosphorylation in HAL-induced liver injury. Pretreatment with U0126 (ERK inhibitor) significantly suppressed the exacerbating effect of progesterone and the expression of inflammatory mediators. In addition, pretreatment with gadolinium chloride (GdCl(3): inhibitor of Kupffer cells) significantly suppressed the exacerbating effect of progesterone pretreatment and the expression of inflammatory mediators. Moreover, posttreatment of RU486 (progesterone receptor antagonist) 1 h after the HAL or TA administration ameliorated the HAL- or TA-induced liver injury, respectively, in female mice. In conclusion, progesterone exacerbated the immune-mediated hepatotoxic responses in DILI via Kupffer cells and ERK pathway. The inhibition of progesterone receptor and decrease of the immune response may have important therapeutic implications in DILI. PMID:22157104

  2. Deep brain stimulation exacerbates hypokinetic dysarthria in a rat model of Parkinson's disease.

    Science.gov (United States)

    King, Nathaniel O; Anderson, Collin J; Dorval, Alan D

    2016-02-01

    Motor symptoms of Parkinson's disease (PD) follow the degeneration of dopaminergic neurons in the substantia nigra pars compacta. Deep brain stimulation (DBS) treats some parkinsonian symptoms, such as tremor, rigidity, and bradykinesia, but may worsen certain medial motor symptoms, including hypokinetic dysarthria. The mechanisms by which DBS exacerbates dysarthria while improving other symptoms are unclear and difficult to study in human patients. This study proposes an animal model of DBS-exacerbated dysarthria. We use the unilateral, 6-hydroxydopamine (6-OHDA) rat model of PD to test the hypothesis that DBS exacerbates quantifiable aspects of vocalization. Mating calls were recorded from sexually experienced male rats under healthy and parkinsonian conditions and during DBS of the subthalamic nucleus. Relative to healthy rats, parkinsonian animals made fewer calls with shorter and less complex vocalizations. In the parkinsonian rats, putatively therapeutic DBS further reduced call frequency, duration, and complexity. The individual utterances of parkinsonian rats spanned a greater bandwidth than those of healthy rats, potentially reducing the effectiveness of the vocal signal. This utterance bandwidth was further increased by DBS. We propose that the parkinsonism-associated changes in call frequency, duration, complexity, and dynamic range combine to constitute a rat analog of parkinsonian dysarthria. Because DBS exacerbates the parkinsonism-associated changes in each of these metrics, the subthalamic stimulated 6-OHDA rat is a good model of DBS-induced hypokinetic dysarthria in PD. This model will help researchers examine how DBS alleviates many motor symptoms of PD while exacerbating parkinsonian speech deficits that can greatly diminish patient quality of life. PMID:26498277

  3. Phenotypic and genetic consequences of protein damage.

    Directory of Open Access Journals (Sweden)

    Anita Krisko

    Full Text Available Although the genome contains all the information necessary for maintenance and perpetuation of life, it is the proteome that repairs, duplicates and expresses the genome and actually performs most cellular functions. Here we reveal strong phenotypes of physiological oxidative proteome damage at the functional and genomic levels. Genome-wide mutations rates and biosynthetic capacity were monitored in real time, in single Escherichia coli cells with identical levels of reactive oxygen species and oxidative DNA damage, but with different levels of irreversible oxidative proteome damage (carbonylation. Increased protein carbonylation correlates with a mutator phenotype, whereas reducing it below wild type level produces an anti-mutator phenotype identifying proteome damage as the leading cause of spontaneous mutations. Proteome oxidation elevates also UV-light induced mutagenesis and impairs cellular biosynthesis. In conclusion, protein damage reduces the efficacy and precision of vital cellular processes resulting in high mutation rates and functional degeneracy akin to cellular aging.

  4. Value of procalcitonin, C-reactive protein, and neopterin in exacerbations of chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Alicia Lacoma

    2011-02-01

    Full Text Available Alicia Lacoma1,4, Cristina Prat1,4, Felipe Andreo2,4, Luis Lores3, Juan Ruiz-Manzano2,4, Vicente Ausina1,4, Jose Domínguez1,41Servei de Microbiologia, 2Servei de Pneumologia, Hospital Universitari Germans Trias i Pujol, Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain; 3Servei de Pneumologia, Hospital de Sant Boi, Sant Boi de Llobregat, Spain; 4CIBER Enfermedades Respiratorias (CIBERES, Instituto de Salud Carlos III, Madrid, SpainObjective: The identification of biological markers in order to assess different aspects of COPD is an area of growing interest. The objective of this study was to investigate whether levels of procalcitonin (PCT, C-reactive protein (CRP, and neopterin in COPD patients could be useful in identifying the etiological origin of the exacerbation and assessing its prognosis.Methods: We included 318 consecutive COPD patients: 46 in a stable phase, 217 undergoing an exacerbation, and 55 with pneumonia. A serum sample was collected from each patient at the time of being included in the study. A second sample was also collected 1 month later from 23 patients in the exacerbation group. We compared the characteristics, biomarker levels, microbiological findings, and prognosis in each patient group. PCT and CRP were measured using an immunofluorescence assay. Neopterin levels were measured using a competitive immunoassay.Results: PCT and CRP showed significant differences among the three patient groups, being higher in patients with pneumonia, followed by patients with exacerbation (P < 0.0001. For the 23 patients with paired samples, PCT and CRP levels decreased 1 month after the exacerbation episode, while neopterin increased. Neopterin showed significantly lower levels in exacerbations with isolation of pathogenic bacteria, but no differences were found for PCT and CRP. No significant differences were found when comparing biomarker levels

  5. Efficacy of a self-management plan in exacerbations for patients with advanced COPD

    Directory of Open Access Journals (Sweden)

    Sánchez-Nieto JM

    2016-08-01

    Full Text Available Juan Miguel Sánchez-Nieto,1,2 Rubén Andújar-Espinosa,3 Roberto Bernabeu-Mora,1,2 Chunshao Hu,1 Beatriz Gálvez-Martínez,1 Andrés Carrillo-Alcaraz,1 Carlos Federico Álvarez-Miranda,3 Olga Meca-Birlanga,1 Eva Abad-Corpa4 1Division of Pneumology, Hospital Morales Meseguer, 2University of Murcia, 3Division of Pneumology, Hospital Arrixaca, Murcia, 4Department of Professional Development Unit, Murcia, Spain Background: Self-management interventions improve different outcome variables in various chronic diseases. Their role in COPD has not been clearly established. We assessed the efficacy of an intervention called the self-management program on the need for hospital care due to disease exacerbation in patients with advanced COPD.Methods: Multicenter, randomized study in two hospitals with follow-up of 1 year. All the patients had severe or very severe COPD, and had gone to either an accident and emergency (A&E department or had been admitted to a hospital at least once in the previous year due to exacerbation of COPD. The intervention consisted of a group education session on the main characteristics of the disease, an individual training session on inhalation techniques, at the start and during the 3rd month, and a written action plan containing instructions for physical activity and treatment for stable phases and exacerbations. We determined the combined number of COPD-related hospitalizations and emergency visits per patient per year. Secondary endpoints were number of patients with visits to A&E and the number of patients hospitalized because of exacerbations, use of antibiotics and corticosteroids, length of hospital stay, and all-cause mortality.Results: After 1 year, the rate of COPD exacerbations with visits to A&E or hospitalization had decreased from 1.37 to 0.89 (P=0.04 and the number of exacerbations dropped from 52 to 42 in the group of patients who received the intervention. The numbers of patients hospitalized, at 19 (40

  6. Potential for Error in Valuing Ecosystem Services Using the Expected Damage Function Approach

    OpenAIRE

    Boutwell, Luke; Westra, John

    2015-01-01

    Communities along the US coast are highly vulnerable to coastal storms. Trends in population growth, climatic events and land use are likely to exacerbate future damages. Coastal management entities are faced with decisions about how to manage resources in a manner that improves environmental quality and provides the maximum benefit for coastal populations. This is particularly true along the coast of the Gulf of Mexico, where coastal storms are common, land loss is rapid and billions of doll...

  7. Inflammation, glucose, and vascular cell damage: the role of the pentose phosphate pathway

    OpenAIRE

    Peiró, Concepción; Romacho, Tania; Azcutia, Verónica; Villalobos, Laura; Fernández, Emilio; Bolaños, Juan P.; Moncada, Salvador; Sánchez-Ferrer, Carlos F

    2016-01-01

    Background Hyperglycemia is acknowledged as a pro-inflammatory condition and a major cause of vascular damage. Nevertheless, we have previously described that high glucose only promotes inflammation in human vascular cells previously primed with pro-inflammatory stimuli, such as the cytokine interleukin (IL)1β. Here, we aimed to identify the cellular mechanisms by which high glucose exacerbates the vascular inflammation induced by IL1β. Methods Cultured human aortic smooth muscle cells (HASMC...

  8. Prompt initiation of maintenance treatment following a COPD exacerbation: outcomes in a large insured population

    Science.gov (United States)

    Coutinho, Anna D; Lokhandwala, Tasneem; Boggs, Robert L; Dalal, Anand A; Landsman-Blumberg, Pamela B; Priest, Julie; Stempel, David A

    2016-01-01

    Background The aim of this study was to extend previous findings and determine the value of prompt initiation of maintenance treatment (MT) following COPD exacerbations requiring hospitalization or an emergency department (ED) visit. Patients and methods Administrative claims data (collected between January 1, 2009 and June 30, 2012) from an employer-sponsored commercially insured population were retrospectively used to identify patients with a COPD exacerbation resulting in hospitalization or an ED visit. Patients initiating approved MT for COPD within 30 days of discharge/diagnosis (prompt) were compared with those initiating MT within 31–180 days (delayed). COPD-related total, medical, and prescription drug costs during a 1-year follow-up period were evaluated using semilog ordinary least square regressions, controlling for baseline characteristics plus COPD-related costs from the previous year. The odds and number of subsequent COPD-related exacerbations during the follow-up were compared between the prompt and delayed cohorts using logistic regression and zero-inflated negative binomial models, respectively. Results A total of 6,521 patients with a COPD-related hospitalization or an ED visit were included, of whom 4,555 received prompt MT and 1,966 received delayed MT. Adjusted COPD-related total and medical costs were significantly lower for the prompt MT than the delayed MT cohorts (US$3,931 vs US$4,857 and US$2,327 vs US$3,087, respectively; both P<0.010), as were COPD-related prescription costs (US$1,526 vs US$1,683, P<0.010) during the 1-year follow-up period. Patients receiving delayed MT were 68% more likely to have a subsequent exacerbation requiring hospitalization and 80% more likely to have an exacerbation requiring an ED visit. Conclusion Prompt initiation of MT following a COPD-related hospitalization or an ED visit was associated with a significant reduction in COPD-related costs and odds of exacerbation in the following year compared with

  9. Differences in care between general medicine and respiratory specialists in the management of patients hospitalized for acute exacerbations of chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Kurugamage Wijayaratne

    2013-01-01

    Full Text Available Context: Hospitalized patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD may be managed by either respiratory specialists (RS or general medicine physicians (GMP. While previous studies have audited the hospital AECOPD management of RS, only a small number of studies have evaluated the management of GMP. Aims: The aims of this study were to firstly examine the differences in AECOPD management of GMP and RS and secondly compare their care to national COPD guidelines. Methods: A retrospective review was undertaken of consecutive AECOPD patients admitted to two hospitals (one hospital where all AECOPD patients were managed by RS and another where all AECOPD patients were managed by GMP over a 3-month period. Electronic medical records, medical case notes, pathology and radiology data for the admission were reviewed. Results: There were 201 COPD exacerbations in 169 patients (49.7% male, mean age 72.3. GMP managed 84 (41.7% exacerbations. In comparison to RS, GMP performed fewer spirometry tests, blood gas analysis and less frequently treated patients with guideline-recommended medications. Referral to pulmonary rehabilitation was poor for both groups of clinicians. Median length of stay was shorter in GMP patients versus RS patients (3 days vs. 5 days, P = 0.001. There were no differences in the 12-month re-admission (41.7% vs. 38.5%, P = 0.664 and mortality rates (10.7% vs. 6%, P = 0.292 between both groups of patients. Conclusion: Our study found differences in the hospital AECOPD management of GMP and RS, but these did not translate into different clinical outcomes between their patients. We also found suboptimal adherence to national COPD guidelines, suggesting that there is scope for improvement in the AECOPD management of both groups of clinicians.

  10. Aging Skin

    Science.gov (United States)

    ... email address Submit Home > Healthy Aging > Wellness Healthy Aging Aging skin More information on aging skin When it ... treated early. Return to top More information on Aging skin Read more from womenshealth.gov Varicose Veins ...

  11. Aging cellular networks: chaperones as major participants

    OpenAIRE

    Soti, Csaba; Csermely, Peter

    2006-01-01

    We increasingly rely on the network approach to understand the complexity of cellular functions. Chaperones (heat shock proteins) are key "networkers", which have among their functions to sequester and repair damaged protein. In order to link the network approach and chaperones with the aging process, we first summarize the properties of aging networks suggesting a "weak link theory of aging". This theory suggests that age-related random damage primarily affects the overwhelming majority of t...

  12. Visualizing the Politics of Innocence in the Age of AIDS

    Science.gov (United States)

    Mitchell, Claudia; Walsh, Shannon; Larkin, June

    2004-01-01

    We are concerned with the ways in which social constructions of age can contribute to reducing or exacerbating the vulnerability of young people, and for this reason we refer to the issue as one of "the politics of innocence". The focus of this paper is on gender, youth and HIV prevention/AIDS awareness in the context of South Africa and…

  13. Appraising Damaged Timber

    OpenAIRE

    Straka, Thomas

    2009-01-01

    Estimation of the value of damaged timber stands can be complicated. The foundation for any valuation calculations involving damaged timber is land expectation value (LEV). A timber damage model using LEV is described in detail. The concept is economically sound as it ignores sunk costs and considers land opportunity cost and the impact on future rotations. The method described is an income approach. The results can also be applied to a replacement cost model. The two approaches will produce ...

  14. Exacerbation of lupus erythematodes visceralis as a result of UV irradiation - a hypothesis

    International Nuclear Information System (INIS)

    In the culture medium of human fibroblasts a proteolytic activity is evident after UV irradiation (290 - 320 nm). The effect of this proteolytic activity on human serum results in an electrophoretic mobility towards the anode of the C3 component of complement, which thus proves to be activated. In discussing recent and former results, a hypothesis on the exacerbation of lupus erythematodes visceralis is presented: UV irradiation causes peroxydation of lipids resulting in the release of proteolytic enzymes from lysosomal membranes and activation of the complemental system. Thus the reactivity of the immune system is increased and the disease becomes exacerbated. Further the following hypothetic aspects are discussed: porphyrins cause enhanced peroxydation of lipids, increased synthesis rate of porphyrins by drugs, decrease of lipid peroxydation by antioxidants, e.g. vitamin E, in relation to possible therapeutic effects

  15. One Center’s Guide to Outpatient Management of Pediatric Cystic Fibrosis Acute Pulmonary Exacerbation

    Science.gov (United States)

    Muirhead, Corinne A.; Sanford, Jillian N.; McCullar, Benjamin G.; Nolt, Dawn; MacDonald, Kelvin D.

    2016-01-01

    Cystic fibrosis (CF) is a chronic disorder characterized by acute pulmonary exacerbations that comprise increased cough, chest congestion, increased mucus production, shortness of breath, weight loss, and fatigue. Typically, severe episodes are treated in the inpatient setting and include intravenous antimicrobials, airway clearance therapy, and nutritional support. Children with less-severe findings can often be managed as outpatients with oral antimicrobials and increased airway clearance therapy at home without visiting the specialty CF center to begin treatment. Selection of specific antimicrobial agents is dependent on pathogens found in surveillance culture, activity of an agent in patients with CF, and the unique physiology of these patients. In this pediatric review, we present our practice for defining acute pulmonary exacerbation, deciding treatment location, initiating treatment either in-person or remotely, determining the frequency of airway clearance, selecting antimicrobial therapy, recommending timing for follow-up visit, and recognizing and managing treatment failures. PMID:27429564

  16. Development and Evaluation of an Automated, Home-Based, Electronic Questionnaire for Detecting COPD Exacerbations

    Directory of Open Access Journals (Sweden)

    Francisco de B. Velazquez-Peña

    2015-01-01

    Full Text Available Collaboration between patients and their medical and technical experts enabled the development of an automated questionnaire for the early detection of COPD exacerbations (AQCE. The questionnaire consisted of fourteen questions and was implemented on a computer system for use by patients at home in an un-supervised environment. Psychometric evaluation was conducted after a 6-month field trial. Fifty-two patients were involved in the development of the questionnaire. Reproducibility was studied using 19 patients (ICC = 0.94. Sixteen out of the 19 subjects started the 6 month-field trial with the computer application. Cronbach’s alpha of 0.81 was achieved. In the concurrent validity analysis, a correlation of 0.80 (p = 0.002 with the CCQ was reported. The results suggest that AQCE is a valid and reliable questionnaire, showing that an automated home-based electronic questionnaire may enable early detection of exacerbations of COPD.

  17. Update on Recent Advances in the Management of Aspirin Exacerbated Respiratory Disease

    OpenAIRE

    Palikhe, Nami Shrestha; Kim, Joo-Hee; Park, Hae-Sim

    2009-01-01

    Aspirin intolerant asthma (AIA) is frequently characterized as an aspirin (ASA)-exacerbated respiratory disease (AERD). It is a clinical syndrome associated with chronic severe inflammation in the upper and lower airways resulting in chronic rhinitis, sinusitis, recurrent polyposis, and asthma. AERD generally develops secondary to abnormalities in inflammatory mediators and arachidonic acid biosynthesis expression. Upper and lower airway eosinophil infiltration is a key feature of AERD; howev...

  18. Does a Nephron Deficit Exacerbate the Renal and Cardiovascular Effects of Obesity?

    OpenAIRE

    Seshini Gurusinghe; Brown, Russell D.; Xiaochu Cai; Samuel, Chrishan S.; Ricardo, Sharon D.; Thomas, Merlin C.; Kett, Michelle M

    2013-01-01

    It has been hypothesized that a reduced nephron endowment exacerbates the hypertensive and renal effects of obesity. We therefore examined the impact of diet-induced obesity on renal structure and function, and arterial pressure in a genetic model of reduced nephron endowment, the GDNF Heterozygous (HET) mouse. 6 wk-old male GDNF WT and HET mice were placed on control or high fat (HFF) diet for 20 weeks. 24 hr arterial pressure, heart rate and activity (radiotelemetry), creatinine clearance a...

  19. Action plans for COPD: strategies to manage exacerbations and improve outcomes

    OpenAIRE

    Jalota L; Jain VV

    2016-01-01

    Leena Jalota,1 Vipul V Jain1,2 1Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of California, San Francisco, 2Chronic Lung Disease Program, UCSF-Fresno, Community Regional Medical Center, Fresno, CA, USA Abstract: COPD is the third-largest killer in the world, and certainly takes a toll on the health care system. Recurrent COPD exacerbations accelerate lung-function decline, worsen mortality, and consume over US$50 billion in health care spendi...

  20. Post-operative acute exacerbation of pulmonary fibrosis in lung cancer patients undergoing lung resection

    OpenAIRE

    YANO, MOTOKI; Sasaki, Hidefumi; MORIYAMA, SATORU; HIKOSAKA, YU; YOKOTA, KEISUKE; Kobayashi, Susumu; HARA, MASAKI; Fujii, Yoshitaka

    2011-01-01

    Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) in lung cancer patients is a critical factor in post-operative mortality. The cause of AE development is unknown and AE may occur in patients without the diagnosis of IPF. We have conducted a retrospective study of consecutive patients who underwent lung cancer surgery since January 2004. Sixty-two patients with fibrous findings in preoperative high-resolution computed tomography were enrolled in the present study and clinicopatho...

  1. Serum heat shock protein 47 levels are elevated in acute exacerbation of idiopathic pulmonary fibrosis

    OpenAIRE

    Kakugawa, Tomoyuki; Yokota, Shin-ichi; Ishimatsu, Yuji; Hayashi, Tomayoshi; Nakashima, Shota; Hara, Shintaro; Sakamoto, Noriho; Kubota, Hiroshi; Mine, Mariko; Matsuoka, Yasuhiro; Mukae, Hiroshi; Nagata, Kazuhiro; Kohno, Shigeru

    2013-01-01

    Little is known about the pathophysiology of acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF). Heat shock protein 47 (HSP47), a collagen-specific molecular chaperone, is essential for biosynthesis and secretion of collagen molecules. Previous studies in experimental animal fibrosis models have shown that downregulation of HSP47 expression reduces collagen production and diminishes fibrosis progression. In this study, serum HSP47 levels were evaluated to elucidate pathogenic diff...

  2. Moxifloxacin in the management of exacerbations of chronic bronchitis and COPD

    OpenAIRE

    Miravitlles, Marc

    2007-01-01

    Bacteria are isolated in more than 50% of exacerbations of chronic bronchitis (CB) and chronic obstructive pulmonary disease (COPD). The most prevalent respiratory pathogens include Gram-positive (Streptococcus pneumoniae) and Gram-negative (Haemophilus influenzae, Moraxella catarrhalis) microorganims. Moxifloxacin is a fourth-generation fluoroquinolone that has been shown to be effective against respiratory pathogens, including atypicals and those resistant to most common antibiotics. The bi...

  3. [Clinical pathway management of acute exacerbations of chronic obstructive pulmonary disease based on state machine].

    Science.gov (United States)

    Tan, Jian; Hao, Liwei; Cheng, Yuanxiong; Xu, Tongliang; Song, Yingnuo

    2014-04-01

    We propose a clinical pathway of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) based on state machine. Clinical event-driven response was utilized to control workflow execution of the AECOPD clinical pathway. By comparison with the traditional clinical pathway management, clinical numerical results showed that the proposed method was better in hospitalization days, average hospitalization expense and aberration rate, and better handled the variability in the AECOPD clinical pathway execution. PMID:24752111

  4. Sputum PGP is reduced by azithromycin treatment in patients with COPD and correlates with exacerbations

    OpenAIRE

    O'Reilly, Philip J.; Jackson, Patricia L; Wells, J. Michael; Dransfield, Mark T; Scanlon, Paul D.; Blalock, J Edwin

    2013-01-01

    Rationale Proline–glycine–proline (PGP), a neutrophil chemoattractant derived from the enzymatic breakdown of collagen, is elevated in sputum of patients with chronic obstructive pulmonary disease (COPD) and may contribute to disease progression. Whether sputum levels of PGP respond to therapy for COPD or predict outcomes is unknown. Objectives We conducted a study ancillary to a multicenter trial of the efficacy of azithromycin treatment for 1 year in preventing COPD exacerbations to test wh...

  5. Pulmonary rehabilitation in copd exacerbation: is upper limbs exercise training safe and effective?

    OpenAIRE

    Ferreira, Dulce; Mendes, Eugénia; Noronha, Bruno; Preto, Leonel; Novo, André

    2015-01-01

    Pulmonary rehabilitation in COPD exacerbation has several advantages such as reduction of hospital readmission and mortality, the considerable increase of quality of life and functional improvement translated into a better outcome in the 6 min walking test. Upper limbs exercise is recommended in pulmonary rehabilitation guidelines because it reduces stress, decreases dyspnea and dynamic hyperinflation and improves functional capacity with impact on daily living activities. This study aimed to...

  6. Higher serum CCL17 may be a promising predictor of acute exacerbations in chronic hypersensitivity pneumonitis

    OpenAIRE

    Miyazaki, Yasunari; Unoura, Koji; Tateishi, Tomoya; Akashi, Takumi; Takemura, Tamiko; Tomita, Makoto; Inase, Naohiko; Yoshizawa, Yasuyuki

    2013-01-01

    Background Recent research has suggested that the Th1 and Th2 chemokine/cytokine axis contributes to the development of chronic hypersensitivity pneumonitis (HP). Acute exacerbations (AE) are significant factors in the prognosis of chronic HP. Little is known, however, about these biomarkers in association with AE in chronic HP patients. Methods Fifty-six patients with chronic HP were evaluated, including 14 patients during episodes of AE. Th1 mediators (C-X-C chemokine ligand [CXCL]10 and in...

  7. A Comparison of Work-Exacerbated Asthma Cases from Clinical and Epidemiological Settings

    OpenAIRE

    Henneberger, Paul K; Xiaoming Liang; Catherine Lemière

    2013-01-01

    BACKGROUND: Clinical and epidemiological studies commonly use different case definitions in different settings when investigating work-exacerbated asthma (WEA). These differences are likely to impact characteristics of the resulting WEA cases.OBJECTIVES: To investigate this issue by comparing two groups of WEA cases, one identified using an intensive clinical evaluation and another that fulfilled epidemiological criteria.METHODS: A total of 53 clinical WEA cases had been referred for suspecte...

  8. Protective Effects of Quetiapine on Metabolic and Inflammatory Abnormalities in Schizophrenic Patients during Exacerbated Stage.

    Science.gov (United States)

    Kao, Yu-Chen; Ko, Chih-Yuan; Wang, Sheng-Chiang; Liu, Yia-Ping

    2016-04-30

    Inflammation has been considered important in the pathogenesis of schizophrenia. Increasing evidence reveals that patients with schizophrenia have abnormal expression of cytokines, which are related to development of metabolic abnormalities. Metabolic abnormality has become a critical issue, though its longitudinal relationship with the disorder, such as the antipsychotics influence, is unclear. We aimed to investigate whether abnormalities of metabolic parameters and cytokine levels in acute exacerbated schizophrenic patients existed, and whether intervention of antipsychotic could help. The present study analyzed peripheral cytokines and metabolic/hemodynamic parameters in healthy controls and acute exacerbated schizophrenic patients hospitalized for three weeks under the unique treatment of quetiapine, a well-known second-generation antipsychotic. Our results showed that patients with schizophrenia were predisposed to metabolic abnormalities in acute exacerbation, including body mass index (BMI) and waist circumference (WC). The patients were also prone to dysglycemia, lower high-density lipoprotein cholesterol (HDL-c) levels, and higher blood pressure with concomitant of elevation of interleukin (IL)-2, IL-6 and IL-10 in which IL-6 was associated with BMI. After quetiapine treatment, IL-2, IL-6 and IL-10 remained higher than the controls, but IL-10 was significantly decreased in follow-up comparison. Glycemic-related indexes, HDL-c and IL-10 levels were significantly changed by variance analysis. Results of the present study imply that acute exacerbated schizophrenic patients with metabolism abnormalities may involve disruption of expression of cytokines, and that quetiapine may have therapeutic effects. Nonetheless, metabolism parameters of patients undergoing treatment with quetiapine should be closely monitored. PMID:27080462

  9. Exacerbated Mechanical Hyperalgesia in Rats with Genetically Predisposed Depressive Behavior: Role of Melatonin and NMDA Receptors

    OpenAIRE

    Wang, Shuxing; Tian, Yinghong; Song, Li; Lim, Grewo; Tan, Yonghui; You, Zerong; Chen, Lucy; Mao, Jianren

    2012-01-01

    A connection between pain and depression has long been recognized in the clinical setting; however, its mechanism remains unclear. In this study, we showed that mechanical hyperalgesia induced by unilateral temporomandibular joint (TMJ) inflammation was exacerbated in Wistar-Kyoto (WKY) rats with genetically predisposed depressive behavior. Reciprocally, TMJ inflammation enhanced depressive behavior such that a lower nociceptive threshold correlated with a higher score of depressive behavior ...

  10. Fecal microbial composition of ulcerative colitis and Crohn's disease patients in remission and subsequent exacerbation.

    Directory of Open Access Journals (Sweden)

    Edgar S Wills

    Full Text Available BACKGROUND: Limited studies have examined the intestinal microbiota composition in relation to changes in disease course of IBD over time. We aimed to study prospectively the fecal microbiota in IBD patients developing an exacerbation during follow-up. DESIGN: Fecal samples from 10 Crohn's disease (CD and 9 ulcerative colitis (UC patients during remission and subsequent exacerbation were included. Active disease was determined by colonoscopy and/or fecal calprotectine levels. Exclusion criteria were pregnancy, antibiotic use, enema use and/or medication changes between consecutive samples. The microbial composition was assessed by 16S rDNA pyrosequencing. RESULTS: After quality control, 6,194-11,030 sequences per sample were available for analysis. Patient-specific shifts in bacterial composition and diversity were observed during exacerbation compared to remission, but overarching shifts within UC or CD were not observed. Changes in the bacterial community composition between remission and exacerbation as assessed by Bray-Curtis dissimilarity, were significantly larger in CD versus UC patients (0.59 vs. 0.42, respectively; p = 0.025. Thiopurine use was found to be a significant cause of clustering as shown by Principal Coordinate Analysis and was associated with decreases in bacterial richness (Choa1 501.2 vs. 847.6 in non-users; p<0.001 and diversity (Shannon index: 5.13 vs. 6.78, respectively; p<0.01. CONCLUSION: Shifts in microbial composition in IBD patients with changing disease activity over time seem to be patient-specific, and are more pronounced in CD than in UC patients. Furthermore, thiopurine use was found to be associated with the microbial composition and diversity, and should be considered when studying the intestinal microbiota in relation to disease course.

  11. Determination of exacerbation predictors in patients with COPD in physical therapy - a longitudinal study

    Directory of Open Access Journals (Sweden)

    Diego M. Marino

    2014-05-01

    Full Text Available Background: Chronic obstructive pulmonary disease (COPD typically presents the characteristic clinical condition of exacerbation, with more intense symptoms associated with greater functional loss and consequently lower chances of patient survival. Objectives: This study sought to determine the predictors of exacerbation, alone or in combination, in patients with chronic obstructive pulmonary disease (COPD who received physical therapeutic treatment over 6 months. Method: This was an observational, longitudinal and prospective study in which 63 COPD patients residing within the municipality of São Carlos, SP, Brazil were evaluated. These patients had COPD stages II and III and were entered into a physical therapy program, consisting of 3 periods of assessment over 6 months. We evaluated the occurrence of acute exacerbation as well as the patients' body mass index (BMI, fat-free mass (FFM, fat-free mass index, forced expiratory volume in 1 second (FEV1, dyspnea, distance walked (DW in the 6-minute walk test (6MWT and handgrip strength. Results: When applying Cox settings with each covariate separately, the results revealed 5% significance only for the DW in the 6MWT, which demonstrated an interaction between BMI and FFM. Comparison of the 3 periods of assessment across the covariates measured showed a significant difference only for the DW between evaluations in the 3rd and 6th months. Conclusion: Upon analyzing the predictors of risk over 6 months of follow-up in patients with COPD, we found that the DW in the 6MWT was associated with the risk of exacerbation, although this risk also depended on the covariates BMI and FFM.

  12. Clinical diaries in COPD: compliance and utility in predicting acute exacerbations

    Directory of Open Access Journals (Sweden)

    Walters EH

    2012-07-01

    Full Text Available E Haydn Walters,1 Julia Walters,1 Karen E Wills,1 Andrew Robinson,2 Richard Wood-Baker11Menzies Research Institute Tasmania, University of Tasmania, Hobart; 2School of Nursing and Midwifery, University of Tasmania, Hobart, AustraliaBackground: Daily diaries are often used to collect data on disease activity, but are burdensome and compliance may be poor. Their use in chronic obstructive pulmonary disease (COPD and impact on the prevention and treatment of exacerbations is poorly researched.Methods: We investigated diary-keeping in COPD and ascertained items that best predicted emergency attendances for exacerbations. Participants in the active limb of a clinical trial in COPD kept daily diaries rating breathlessness, cough, sputum, physical activity, and use of reliever medication.Results: Data on 55 participants, 67% of whom were female, showed that overall compliance with diary-keeping was 62%. Participants educated to primary school level only had lower compliance (P = 0.05. Twenty patients had at least one emergency attendance, in whom the relative risk of an acute exacerbation for an increase in item score rose from six days prior to hospitalization, most sharply in the last two days. Even for optimal combinations of items, the positive predictive value was poor, the best combination being cough, activity level, and inhaler use.Conclusion: Good compliance can be achieved using daily diaries in COPD, although this is worse in those with a poor educational level. Diary-keeping is not accurate in predicting acute exacerbations, but could be substantially simplified without loss of efficiency.Keywords: chronic obstructive pulmonary disease, daily diary, secondary prevention

  13. Outcomes of acute exacerbations in COPD in relation to pre-hospital oxygen therapy

    OpenAIRE

    Ringbaek, Thomas J.; Terkelsen, Jakob; Lange, Peter

    2015-01-01

    Background: Pre-hospital, high-concentration oxygen therapy during acute exacerbation of chronic obstructive pulmonary disease (AECOPD) has been associated with increased mortality. Recent COPD guidelines have encouraged titrated oxygen therapy with a target saturation range of 88–92%. Oxygen therapy leading to saturation above 92% is defined as ‘inappropriate oxygen therapy’.Objectives: To examine the frequency of inappropriate oxygen therapy and whether inappropriate oxygen therapy in the a...

  14. Effects of Vitamin D Intake on FEV1 and COPD Exacerbation: A Randomized Clinical Trial Study

    OpenAIRE

    2015-01-01

    Aim: This study aimed to evaluate the effects of vitamin D intake on COPD exacerbation and FEV1 in the patients with severe and very severe COPD. Methods: This double blind placebo control randomized clinical trial study was done in the Ashayer university hospital in Khorramabad in 2012. Eighty eight patients with severe and very severe COPD were randomly selected from those who recoursed to the internal medicine clinic of Ashayer hospital. They were randomly allocated to case and placebo gro...

  15. Allergic Conjunctivitis Exacerbates Corneal Allograft Rejection by Activating Th1 and Th2 Alloimmune Responses

    OpenAIRE

    Niederkorn, Jerry Y.; Chen, Peter W.; Mellon, Jessamee; Stevens, Christina; Mayhew, Elizabeth

    2010-01-01

    Allergic conjunctivitis (AC) and airway hyperreactivity exacerbate corneal allograft rejection. Because AC and airway hyperreactivity are allergic diseases of mucosal tissues, we determined whether an allergic disease of a nonmucosal tissue would affect corneal allograft rejection and whether Th2 cells alone accounted for accelerated graft rejection in allergic mice. Hosts sensitized cutaneously with short ragweed pollen developed cutaneous immediate hypersensitivity but rejected corneal allo...

  16. Implicit state guarantees exacerbate problem: Separated banking system alone not a solution

    OpenAIRE

    Klaus, Benjamin; Schäfer, Dorothea

    2013-01-01

    Many banks are now too big, complex, and closely interconnected to be liquidated. When they run into difficulties, they threaten the entire financial system of their economic area. Five years of financial crisis have not alleviated but exacerbated this problem. The cost of stabilizing banks is enormous, posing serious challenges to the states affected. In addition, such state guarantees create dangerously false incentives: they encourage managers and investors to engage into high risk-taking,...

  17. The Impact of Respiratory Viral Infection on Wheezing Illnesses and Asthma Exacerbations

    OpenAIRE

    Carroll, Kecia N.; Hartert, Tina V

    2008-01-01

    The etiology and morbidity associated with asthma are thought to stem from both genetic factors and potentially modifiable environmental factors, such as viral infections.[1-7] Although it is unclear whether respiratory viral infections cause asthma, observational studies have demonstrated a high rate of asthma in children with a history of severe viral lower respiratory tract infections during infancy, and viruses are the associated with the majority of asthma exacerbations among both childr...

  18. Anxiety Interacts With Expressed Emotion Criticism in the Prediction of Psychotic Symptom Exacerbation

    OpenAIRE

    Docherty, Nancy M.; St-Hilaire, Annie; Aakre, Jennifer M.; Seghers, James P.; McCleery, Amanda; Divilbiss, Marielle

    2009-01-01

    Psychotic symptoms are exacerbated by social stressors in schizophrenia and schizoaffective disorder patients as a group. More specifically, critical attitudes toward patients on the part of family members and others have been associated with a higher risk of relapse in the patients. Some patients appear to be especially vulnerable in this regard. One variable that could affect the degree of sensitivity to a social stressor such as criticism is the individual’s level of anxiety. The present l...

  19. Spirometry for patients in hospital and one month after admission with an acute exacerbation of COPD

    OpenAIRE

    Rea H; Kenealy T; Adair J; Robinson E; Sheridan N

    2011-01-01

    Harry Rea1, Timothy Kenealy1, Jacqui Adair1, Elizabeth Robinson2, Nicolette Sheridan31Section of Integrated Care, South Auckland Clinical School, University of Auckland, 2Biostatistics and Epidemiology, School of Population Health, University of Auckland, 3Section of Integrated Care, South Auckland Clinical School and School of Nursing, University of Auckland, Auckland, New ZealandAim: To assess whether spirometry done in hospital during an admission for an acute exacerbation of chronic obstr...

  20. Confirmatory spirometry for adults hospitalized with a diagnosis of asthma or chronic obstructive pulmonary disease exacerbation

    OpenAIRE

    Prieto Centurion Valentin; Huang Frank; Naureckas Edward T; Camargo Jr Carlos A; Charbeneau Jeffrey; Joo Min J; Press Valerie G; Krishnan Jerry A

    2012-01-01

    Abstract Background Objective measurement of airflow obstruction by spirometry is an essential part of the diagnosis of asthma or COPD. During exacerbations, the feasibility and utility of spirometry to confirm the diagnosis of asthma or chronic obstructive pulmonary disease (COPD) are unclear. Addressing these gaps in knowledge may help define the need for confirmatory testing in clinical care and quality improvement efforts. This study was designed to determine the feasibility of spirometry...

  1. Management and survival of patients admitted with an exacerbation of COPD: comparison of two Danish patient cohorts

    DEFF Research Database (Denmark)

    Eriksen, Nanna; Vestbo, Jørgen

    2010-01-01

    discharged patients admitted in 2006-2007 with an exacerbation of chronic obstructive pulmonary disease from three respiratory departments. Data were collected from patient charts and compared with a replicate study done in 2001. RESULTS:  The mean age was 72.1years; 61.7% were women. Mean forced expiratory...... volume in 1s was 37.6% of predicted. On admission, 11.3% were treated with non-invasive ventilation, and 84.3% were given systemic corticosteroids. In-hospital mortality was 4.7%. At discharge, treatment with inhaled corticosteroids or at least one long-acting bronchodilator was given to 86.7% and 89% of......months following discharge was 42.3%. Long-term oxygen treatment, treatment with anti-dysrhythmic drugs and lack of outpatient follow-up were independent predictors of 1-year mortality. Risk of readmission was increased with dependence in self-care activities, previous admissions and treatment with...

  2. Linking Asthma Exacerbation and Air Pollution Data: A Step Toward Public Health and Environmental Data Integration

    Science.gov (United States)

    Faruque, Fazlay; Finley, Richard; Marshall, Gailen; Brackin, Bruce; Li, Hui; Williams, Worth; Al-Hamdan, Mohammad; Luvall, Jeffrey; Rickman, Doug; Crosson, Bill

    2006-01-01

    Studies have shown that reducing exposure to triggers such as air pollutants can reduce symptoms and the need for medication in asthma patients. However, systems that track asthma are generally not integrated with those that track environmental hazards related to asthma. Tlvs lack of integration hinders public health awareness and responsiveness to these environmental triggers. The current study is a collaboration between health and environmental professionals to utilize NASA-derived environmental data to develop a decision support system (DSS) for asthma prediction, surveillance, and intervention. The investigators link asthma morbidity data from the University of Mississippi Medical Center (UMMC) and Mississippi Department of Health (MDH) with air quality data from the Mississippi Department of Environmental Quality (MDEQ) and remote sensing data from NASA. Daily ambient environmental hazard data for PM2.5 and ozone are obtained from the MDEQ air quality monitoring locations and are combined with remotely sensed data from NASA to develop a state-wide spatial and time series profile of environmental air quality. These data are then used to study the correlation of these measures of air quality variation with the asthma exacerbation incidence throughout the state over time. The goal is to utilize these readily available measures to allow real-time risk assessment for asthma exacerbations. GeoMedStat, a DSS previously developed for biosurveillance, will integrate these measures to monitor, analyze and report the real-time risk assessment for asthma exacerbation throughout the state.

  3. Reduction of Oxidative Stress Attenuates Lipoapoptosis Exacerbated by Hypoxia in Human Hepatocytes

    Directory of Open Access Journals (Sweden)

    Sang Youn Hwang

    2015-02-01

    Full Text Available Chronic intermittent hypoxia, a characteristic of obstructive sleep apnea (OSA, is associated with the progression of simple hepatic steatosis to necroinflammatory hepatitis. We determined whether inhibition of a hypoxia-induced signaling pathway could attenuate hypoxia-exacerbated lipoapoptosis in human hepatocytes. The human hepatocellular carcinoma cell line (HepG2 was used in this study. Palmitic acid (PA-treated groups were used for two environmental conditions: Hypoxia (1% O2 and normoxia (20% O2. Following the treatment, the cell viability was determined by the 3,4-(5-dimethylthiazol-2-yl-5-(3-carboxymethoxyphenyl-2-(4-sulfophenyl-2H-tetrazolium salt (MTS assay, and the mechanism of lipoapoptosis was evaluated by Western blotting. Hypoxia exacerbated the suppression of hepatocyte growth induced by palmitic acid via activation of mitochondrial apoptotic pathways as a result of endoplasmic reticulum (ER and oxidative stresses. Ammonium pyrrolidine dithiocarbamate, a scavenger of reactive oxygen species, attenuated the hypoxia-exacerbated lipoapoptosis in hepatocytes, whereas glycerol, which reduces ER stress, did not. This may have been because inhibition of oxidative stress decreases the expression of pro-apoptotic proteins, such as caspase 9 and cytochrome c. These results suggested that modulation of apoptotic signaling pathways activated by oxidative stress can aid in identifying novel therapeutic strategies for the treatment of nonalcoholic steatohepatitis (NASH with OSA. Further in vivo studies are necessary to understand the pathophysiologic mechanism of NASH with OSA and to prove the therapeutic effect of the modulation of the signaling pathways.

  4. Particulate matter air pollution exposure: role in the development and exacerbation of chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Sean H Ling

    2009-06-01

    Full Text Available Sean H Ling, Stephan F van EedenJames Hogg iCAPTURE Centre for Pulmonary and Cardiovascular Research and Heart and Lung Institute, University of British Columbia, Vancouver, British Columbia, CanadaAbstract: Due to the rapid urbanization of the world population, a better understanding of the detrimental effects of exposure to urban air pollution on chronic lung disease is necessary. Strong epidemiological evidence suggests that exposure to particulate matter (PM air pollution causes exacerbations of pre-existing lung conditions, such as, chronic obstructive pulmonary disease (COPD resulting in increased morbidity and mortality. However, little is known whether a chronic, low-grade exposure to ambient PM can cause the development and progression of COPD. The deposition of PM in the respiratory tract depends predominantly on the size of the particles, with larger particles deposited in the upper and larger airways and smaller particles penetrating deep into the alveolar spaces. Ineffective clearance of this PM from the airways could cause particle retention in lung tissues, resulting in a chronic, low-grade inflammatory response that may be pathogenetically important in both the exacerbation, as well as, the progression of lung disease. This review focuses on the adverse effects of exposure to ambient PM air pollution on the exacerbation, progression, and development of COPD.Keywords: chronic obstructive pulmonary disease, particulate matter, air pollution, alveolar macrophage

  5. Time course and recovery of arterial blood gases during exacerbations in adults with Cystic Fibrosis.

    LENUS (Irish Health Repository)

    Waterhouse, D F

    2012-02-01

    INTRODUCTION: Hypoxia and hypercapnia are closely linked to morbidity and mortality in patients with Cystic Fibrosis (CF). The aims of this study were to describe the changes in blood gases during and following an acute pulmonary exacerbation in adults with CF. METHODS: We performed a prospective observational study of patients with CF admitted for management of an acute exacerbation. Blood gas and spirometric analysis was performed on admission, throughout the treatment period, and 31 days after discharge (day 45). RESULTS: At presentation, eight of nineteen patients had evidence of either hypoxia (PaO(2)<8 kPa) and\\/or hypercapnia (PaCO(2)>6.6 kPa). Blood gas parameters stabilized following two weeks of intravenous antibiotic therapy, with little difference evident in between treatment completion and subsequent review following discharge. Hypercapnia reversed in three patients, with persistent hypercapnia evident in two patients. CONCLUSION: In our study group, hypoxemia and hypercapnia were frequently observed at presentation of the acute exacerbation. Blood gases stabilized following two weeks of intravenous antibiotic therapy, with arterial PCO(2) one month following hospital discharge generally similar to that at time of discharge.

  6. [Clinical contribution of the newer fluoroquinolones in acute bacterial exacerbation of chronic bronchitis].

    Science.gov (United States)

    Niederman, M S

    1999-01-01

    Acute exacerbations occur frequently in patients with chronic bronchitis and the majority of these patients benefit from antimicrobial therapy. The ideal antimicrobial agent for the management of acute exacerbations of chronic bronchitis (AECB) should have good activity against the common bacterial pathogens associated with these exacerbations (non-typable Haemophilus influenzae, Moraxella catarrhalis and pneumococci); it should be resistant to bacterial betalactamases; penetrate well into pulmonary tissues and secretions; kill bacteria without inducing excessive airway inflammation; be easy to take (given once or twice a day) in order to ensure high patient compliance, and be cost-effective. Fluoroquinolone antibiotics have demonstrated efficacy in the treatment of AECB, but because of the limited activity of certain older agents in this class when administered in standard doses against Streptococcus pneumoniae, they have not be extensively used for this indication. Newer agents including levofloxacin, grepafloxacin, sparfloxacin and trovafloxacin have excellent activity against both Gram positive and Gram negative pathogens likely to be involved in AECB. These agents can be administered once daily, making patient compliance and a successful therapeutic outcome more likely. The new quinolones offer promising alternatives for antimicrobial therapy in outpatients with AECB, particularly those with underlying co-morbidity and severe obstruction. PMID:10436551

  7. Antibiotics for bronchiectasis exacerbations in children: rationale and study protocol for a randomised placebo-controlled trial

    Directory of Open Access Journals (Sweden)

    Chang Anne B

    2012-08-01

    Full Text Available Abstract Background Despite bronchiectasis being increasingly recognised as an important cause of chronic respiratory morbidity in both indigenous and non-indigenous settings globally, high quality evidence to inform management is scarce. It is assumed that antibiotics are efficacious for all bronchiectasis exacerbations, but not all practitioners agree. Inadequately treated exacerbations may risk lung function deterioration. Our study tests the hypothesis that both oral azithromycin and amoxicillin-clavulanic acid are superior to placebo at improving resolution rates of respiratory exacerbations by day 14 in children with bronchiectasis unrelated to cystic fibrosis. Methods We are conducting a bronchiectasis exacerbation study (BEST, which is a multicentre, randomised, double-blind, double-dummy, placebo-controlled, parallel group trial, in five centres (Brisbane, Perth, Darwin, Melbourne, Auckland. In the component of BEST presented here, 189 children fulfilling inclusion criteria are randomised (allocation-concealed to receive amoxicillin-clavulanic acid (22.5 mg/kg twice daily with placebo-azithromycin; azithromycin (5 mg/kg daily with placebo-amoxicillin-clavulanic acid; or placebo-azithromycin with placebo-amoxicillin-clavulanic acid for 14 days. Clinical data and a paediatric cough-specific quality of life score are obtained at baseline, at the start and resolution of exacerbations, and at day 14. In most children, blood and deep nasal swabs are also collected at the same time points. The primary outcome is the proportion of children whose exacerbations have resolved at day 14. The main secondary outcome is the paediatric cough-specific quality of life score. Other outcomes are time to next exacerbation; requirement for hospitalisation; duration of exacerbation; and spirometry data. Descriptive viral and bacteriological data from nasal samples and blood markers will also be reported. Discussion Effective, evidence-based management

  8. Efficacy and safety of once-monthly injection of paliperidone palmitate in hospitalized Asian patients with acute exacerbated schizophrenia: an open-label, prospective, noncomparative study

    Directory of Open Access Journals (Sweden)

    Li HF

    2015-12-01

    Full Text Available HuaFang Li,1 Ibrahim Turkoz,2 Fan Zhang3 1Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Janssen Research & Development, LLC, Titusville, NJ, USA; 3Xi’an Janssen Pharmaceutical Ltd., Beijing, People’s Republic of China Introduction: This single-group, open-label, prospective, noncomparative, multicenter, Phase IV study explored the efficacy and tolerability of paliperidone palmitate (PP in hospitalized patients with acute exacerbation of schizophrenia.Methods: Asian patients of either sex, between 18 and 65 years of age, diagnosed with schizophrenia (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition with acute exacerbations within the previous 4 weeks, were enrolled. Intramuscular PP was initiated at doses of 150 milligram equivalent (mg eq (day 1 and 100 mg eq (day 8, followed by a monthly maintenance dose between 75 mg eq and 150 mg eq (days 36 and 64. Primary efficacy endpoint was the change from baseline in the Positive and Negative Syndrome Scale (PANSS total score (last-observation-carried-forward at week 13.Results: Of the 212 enrolled patients, 152 (71.7% completed the 13-week treatment; withdrawal of consent (24 [11.3%] patients was the most common reason for study discontinuation. Mean (standard deviation PANSS total score from baseline (90.0 [17.41] improved significantly at day 4 (-6.1 [9.27]; 95% confidence interval: -7.38, -4.85; P<0.001 and week 13 endpoint (-23.9 [23.24]; 95% confidence interval: -27.10, -20.78; P<0.001. Similarly, the secondary endpoints (Clinical Global Impression-Severity, Physical and Social Performance, each PANSS subscale, and Marder factor scores improved significantly from baseline to week 13 endpoint (P<0.001 for all. At week 13, 112/210 (53.3% patients had a 40% improvement in the PANSS total score (responder rate, and 133/212 (62.7% patients were ready for hospital discharge. Overall, 139 (65

  9. Five-day regimen of intramuscular or subcutaneous self-administered adrenocorticotropic hormone gel for acute exacerbations of multiple sclerosis: a prospective, randomized, open-label pilot trial

    Directory of Open Access Journals (Sweden)

    Simsarian JP

    2011-07-01

    Full Text Available James P Simsarian, Carol Saunders, D Michelle SmithNeurology Center of Fairfax Ltd, Fairfax, VA, USABackground: Despite over 50 years of experience with adrenocorticotropic hormone (ACTH as a treatment for acute exacerbations of multiple sclerosis, there have been no trials examining the options of the 2–3-week dosing regimen or intramuscular injection protocol used in the original trials. At our clinic, we performed a small, prospective, randomized pilot study to examine the efficacy and safety of, and patient satisfaction with, a short (five-day self-administered ACTH dosing protocol for exacerbations of multiple sclerosis, and to compare the subcutaneous and intramuscular routes of administration.Methods: Patients for this study were recruited from an outpatient treatment clinic. Each patient self-administered natural ACTH gel 80 U/day by subcutaneous or intramuscular injection for five consecutive days and was evaluated at baseline and on days 7 and 14. Patient feedback was collected using the Patient Global Impression of Change (PGI-C, the primary efficacy measure, a patient global visual analog scale, the Expanded Disability Status Scale, a timed walk, the Nine-hole Peg Test, and the Clinical Global Impression of Change.Results: Of the 20 enrolled patients (mean age 39.5 years, 19 completed the study. On day 14, 61.1% of patients (11 of 18 with day 14 scores were treatment responders, and rated their condition as "very much improved" or "much improved" on the PGI-C. The intramuscular group had numerically more responders, but there was no significant difference in the proportion of responders between the intramuscular and subcutaneous groups at day 14 (P = 0.3. The intramuscular route of injection was associated with more injection site pain than the subcutaneous route.Conclusion: A shorter five-day course of intramuscular or subcutaneous ACTH gel may improve symptoms associated with acute exacerbations of multiple sclerosis. Larger

  10. Tetracycline in uranyl nitrate intoxication: Its action on renal damage and U retention in bone

    International Nuclear Information System (INIS)

    In acute intoxication, uranium (U) not only inhibits bone formation but its excretion in urine also causes renal damage. The former effect is ameliorated by tetracycline (TC), probably due to its chelation property, which might also prevent U deposition in bone. Chemical determination of U incorporated in bone and a histological study of the kidneys were performed on animals injected with U and then treated with TC. The results showed that TC was unable to prevent the binding of U to bone while it exacerbated U-induced renal damage

  11. DNA damage and autophagy

    International Nuclear Information System (INIS)

    Both exogenous and endogenous agents are a threat to DNA integrity. Exogenous environmental agents such as ultraviolet (UV) and ionizing radiation, genotoxic chemicals and endogenous byproducts of metabolism including reactive oxygen species can cause alterations in DNA structure (DNA damage). Unrepaired DNA damage has been linked to a variety of human disorders including cancer and neurodegenerative disease. Thus, efficient mechanisms to detect DNA lesions, signal their presence and promote their repair have been evolved in cells. If DNA is effectively repaired, DNA damage response is inactivated and normal cell functioning resumes. In contrast, when DNA lesions cannot be removed, chronic DNA damage triggers specific cell responses such as cell death and senescence. Recently, DNA damage has been shown to induce autophagy, a cellular catabolic process that maintains a balance between synthesis, degradation, and recycling of cellular components. But the exact mechanisms by which DNA damage triggers autophagy are unclear. More importantly, the role of autophagy in the DNA damage response and cellular fate is unknown. In this review we analyze evidence that supports a role for autophagy as an integral part of the DNA damage response.

  12. Nuclear damage - civil liability

    International Nuclear Information System (INIS)

    An analysis is made of the civil liability for nuclear damage since there is a need to adjust the existing rules to the new situations created. The conventions that set up the new disciplining rules not considered in the common law for the liability of nuclear damage are also mentioned. (A.L.)

  13. Ischemia-Reperfusion Damage

    OpenAIRE

    Yapca, Omer E.; Borekci, Bunyamin; Suleyman, Halis

    2013-01-01

    Ischemia-reperfusion damage is a complex pathological process that begins with tissue anoxia and continues with the production of free oxygen radicals, expanding with the inflammatory response. The literature suggests the importance of antioxidant and anti-inflammatory treatment to treat ischemia-reperfusion-related tissue damage.

  14. Treatment of patients with COPD and recurrent exacerbations: the role of infection and inflammation

    Directory of Open Access Journals (Sweden)

    Santos S

    2016-03-01

    Full Text Available Salud Santos,1,2 Alicia Marin,2,3 Joan Serra-Batlles,4 David de la Rosa,5 Ingrid Solanes,6 Xavier Pomares,7 Marta López-Sánchez,1 Mariana Muñoz-Esquerre,1 Marc Miravitlles2,81Pneumology Department, Hospital Universitari de Bellvitge, Universidad de Barcelona, Bellvitge Biomedical Research Institute (IDIBELL, Hospitalet de Llobregat, Barcelona, 2Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES, Madrid, 3Pneumology Department, Hospital Universitari Germans Trias i Pujol, Badalona, 4Pneumology Department, Hospital Universitari de Vic, 5Pneumology Unit, Hospital Plató, 6Pneumology Department, Biomedical Research Institute Sant Pau, Hospital de la Santa Creu i Sant Pau, Universidad Autónoma, Barcelona, 7Pneumology Department, Hospital Universitari Parc Taulí, Sabadell, 8Pneumology Department, Hospital Universitari Vall d’Hebron, Barcelona, SpainAbstract: Exacerbations of COPD represent an important medical and health care problem. Certain susceptible patients suffer recurrent exacerbations and as a consequence have a poorer prognosis. The effects of bronchial infection, either acute or chronic, and of the inflammation characteristic of the disease itself raise the question of the possible role of antibiotics and anti-inflammatory agents in modulating the course of the disease. However, clinical guidelines base their recommendations on clinical trials that usually exclude more severe patients and patients with more comorbidities, and thus often fail to reflect the reality of clinicians attending more severe patients. In order to discuss aspects of clinical practice of relevance to pulmonologists in the treatment and prevention of recurrent exacerbations in patients with severe COPD, a panel discussion was organized involving expert pulmonologists who devote most of their professional activity to day hospital care. This article summarizes the scientific evidence currently available and the debate generated in

  15. Tree damage and mycotrophy

    Energy Technology Data Exchange (ETDEWEB)

    Heyser, W.; Iken, J.; Meyer, F.H.

    1988-10-22

    Tree species that are particularly endangered in our forests are characterized by the fact that they live in an obligatory symbiosis with ectomycorrhiza fungii. In verifying which tree species appear to be more damaged or less severely damaged, a conspicuous phenomenon noted was that the tree species exhibiting slight symptoms of damage or none at all included such ones as form mycorrhizas facultatively or dispense with mycorrhizas, e.g. Acer, Aesculus, Fraxinus, Populus, Salix. Given that trees in municipal gardens reflect the development and extent of damage in a way similar to forests, and given also that much greater numbers of tree species are often cultured in parks of this type, the latter were considered particularly suited to examine the question of whether a relationship exists between mycotrophy and the severity of damage.

  16. Study of the fatigue behaviour and damage of a aged duplex stainless steel; Etude du comportement et de l'endommagement en fatigue d'un acier inoxydable austeno-ferritique moule vieilli

    Energy Technology Data Exchange (ETDEWEB)

    Le Roux, J.Ch

    2000-07-01

    Cast duplex stainless steels are commonly used in components of pressurized water reactors primary circuit. When submitted to in-service temperatures embrittlement occurs because of the nucleation and growth of a harder phase in the ferrite by spinodal composition. Macrostructure of this steel (ferritic primary grain size is about 4-5 mm) and embrittlement of ferrite due to aging lead to a very high scattering of mechanical properties for monotonous loadings. We showed that, in spite of this macrostructure, the cyclic behaviour of aged duplex stainless steels fits usual Manson-Coffin law while initial hardening is followed by softening, in part because of the demodulation of the composition. The fatigue crack propagation rate of material follows a Paris law. While crack initiation mainly appears next to the millimetric cast defects, fatigue crack propagation remains a continuous mechanism. Ferritic and austenitic elements break successively (ferrite first breaks by cleavage, then austenite breaks by ductile fatigue). In spite of the fact that the aged ferrite is embrittled, cleavage microcracks, for load levels examined, seldom appear in ferrite at the crack tip and on both sides of the main crack. Effects of cast defects and crystallographic ferrite orientation were also studied. Propagation fatigue crack behaviour was modeled assuming that the crack tip material behaves as if it was submitted to low cycle fatigue loadings. If we consider a homogeneous material, results are in good agreement with experiments. (authors)

  17. Targeting IL-1β and IL-17A driven inflammation during influenza-induced exacerbations of chronic lung inflammation.

    OpenAIRE

    Sichelstiel A.; Yadava K.; Trompette A.; Salami O; Iwakura Y.; Nicod L.P.; Marsland B.J.

    2014-01-01

    For patients with chronic lung diseases, such as chronic obstructive pulmonary disease (COPD), exacerbations are life-threatening events causing acute respiratory distress that can even lead to hospitalization and death. Although a great deal of effort has been put into research of exacerbations and potential treatment options, the exact underlying mechanisms are yet to be deciphered and no therapy that effectively targets the excessive inflammation is available. In this study, we report that...

  18. Targeting IL-1β and IL-17A Driven Inflammation during Influenza-Induced Exacerbations of Chronic Lung Inflammation

    OpenAIRE

    Sichelstiel, Anke; Yadava, Koshika; Trompette, Aurélien; Salami, Olawale; Iwakura, Yoichiro; Nicod, Laurent P.; Marsland, Benjamin J

    2014-01-01

    For patients with chronic lung diseases, such as chronic obstructive pulmonary disease (COPD), exacerbations are life-threatening events causing acute respiratory distress that can even lead to hospitalization and death. Although a great deal of effort has been put into research of exacerbations and potential treatment options, the exact underlying mechanisms are yet to be deciphered and no therapy that effectively targets the excessive inflammation is available. In this study, we report that...

  19. Predicting and reducing risk of exacerbations in children with asthma in the primary care setting: current perspectives

    OpenAIRE

    Turner, Steve

    2016-01-01

    Steve Turner Child Health, Royal Aberdeen Children’s Hospital, University of Aberdeen, Aberdeen, UK Abstract: Childhood asthma is a very common condition in western countries and is becoming more prevalent worldwide. Asthma attacks (or exacerbations) affect the quality of life for child and parent, can rarely result in death, and also come at a cost for health care providers and the economy. The aims of this review were to 1) describe the burden of asthma exacerbations, 2) describe ...

  20. Rhinovirus‐associated pulmonary exacerbations show a lack of FEV 1 improvement in children with cystic fibrosis

    OpenAIRE

    Cousin, Mathias; Molinari, Nicolas; Foulongne, Vincent; Caimmi, Davide; Vachier, Isabelle; Abely, Michel; Chiron, Raphael

    2016-01-01

    Background Respiratory viral infections lead to bronchial inflammation in patients with cystic fibrosis, especially during pulmonary exacerbations. The aim of this study was to determine the impact of viral‐associated pulmonary exacerbations in children with cystic fibrosis and failure to improve forced expiratory volume in 1 s (FEV 1) after an appropriate treatment. Methods We lead a pilot study from January 2009 until March 2013. Children with a diagnosis of cystic fibrosis were longitudina...

  1. A single infection with Chlamydia pneumoniae is sufficient to exacerbate atherosclerosis in ApoE deficient mice

    OpenAIRE

    Sorrentino, Rosalinda; Yilmaz, Atilla; Schubert, Katja; Crother, Timothy R.; Pinto, Aldo; Shimada, Kenichi; Arditi, Moshe; Chen, Shuang

    2015-01-01

    Several studies have demonstrated a strong link between Chlamydia pneumoniae (Cp) infection and atherosclerosis progression/exacerbation. Here, we try to understand whether a single administration of Cp could exacerbate atherosclerosis. Apoe−/− mice were intranasally infected with Cp followed by a high fat diet. Mice were sacrificed at different time points after Cp infection to monitor the development of the atheroma. Cp infection increased lipid content in the aortic sinus of Apoe−/− mice s...

  2. Fecal Microbial Composition of Ulcerative Colitis and Crohn’s Disease Patients in Remission and Subsequent Exacerbation

    OpenAIRE

    Edgar S Wills; Jonkers, Daisy M. A. E.; Paul H Savelkoul; Masclee, Ad A.; Pierik, Marieke J.; John Penders

    2014-01-01

    BACKGROUND: Limited studies have examined the intestinal microbiota composition in relation to changes in disease course of IBD over time. We aimed to study prospectively the fecal microbiota in IBD patients developing an exacerbation during follow-up. DESIGN: Fecal samples from 10 Crohn's disease (CD) and 9 ulcerative colitis (UC) patients during remission and subsequent exacerbation were included. Active disease was determined by colonoscopy and/or fecal calprotectine levels. Exclusion crit...

  3. A comparison of Oral and Inhalant Corticosteroids in Treatment of Mild to Moderate Asthma Exacerbation in Children

    Directory of Open Access Journals (Sweden)

    Nemat Bilan

    2015-04-01

    Full Text Available Introduction: Oral corticosteroids are the main treatment in asthma exacerbation. It has been reported that inhaled corticosteroids can be used instead of oral corticosteroids in asthma exacerbation. We aimed to evaluate the efficacy of inhaled fluticasone and oral prednisolone in children with mild to moderate asthma exacerbation. Materials and Methods: In this randomized clinical trial, 60 children with mild-to-moderate acute asthma exacerbation visiting emergency department were randomly assigned to receive oral prednisolone (2 mg/kg or fluticasone spray (2 puffs every 12 hours, each puff contains 250 microgram fluticasone using an spacer for one week. The first dose of the treatment was given in the emergency department.  Children were followed for seven days and signs and symptoms of exacerbation, as well as spirometry findings were evaluated.Results: On the days 1 and 3, symptoms including cough, sputum and need for salbutamol during day was more improved in oral prednisolone and symptoms at night was more improved in inhaled fluticasone. Patients were almost symptom free on the seventh day. Forced expiratory volume in 1 second, forced vital capacity and forced expiratory flow rate on the seventh day were significantly better with inhaled fluticasone compared to oral prednisolone.Conclusion: Both inhaled fluticasone and oral prednisolone improved symptoms during a week after exacerbation; however, better respiratory function in children treated with inhaled fluticasone is indicative of its further efficacy compared to oral prednisolone. Considering the low systemic effects of inhaled fluticasone, this treatment seems to be more appropriate in treatment of mild to moderate exacerbations. Keywords: Asthma exacerbation; Inhaled fluticasone; Prednisolone

  4. Impact of an educational intervention on steroid prescribing and dosing effect on patient outcomes in COPD exacerbations

    OpenAIRE

    Hope NH; Ray SM; Franks AS; Heidel E

    2010-01-01

    The increasing number of patients affected by chronic obstructive pulmonary disease (COPD) and associated exacerbations has led to both rising hospital admissions and significant economic impact. Evidence-based guidelines have been formulated for COPD management recommending the use of low dose, oral corticosteroid therapy in the treatment of exacerbations. However, fewer than 50% of physicians’ prescribing practices appropriately reflect the published clinical guidelines on the use of system...

  5. Heart rate variability and target organ damage in hypertensive patients

    OpenAIRE

    Melillo Paolo; Izzo Raffaele; Luca De Nicola; Pecchia Leandro

    2012-01-01

    Abstract Background We evaluated the association between linear standard Heart Rate Variability (HRV) measures and vascular, renal and cardiac target organ damage (TOD). Methods A retrospective analysis was performed including 200 patients registered in the Regione Campania network (aged 62.4 ± 12, male 64%). HRV analysis was performed by 24-h holter ECG. Renal damage was assessed by estimated glomerular filtration rate (eGFR), vascular damage by carotid intima-media thickness (IMT), and card...

  6. Update on the oxidative stress theory of aging: Does oxidative stress play a role in aging or healthy aging?

    OpenAIRE

    Salmon, Adam B.; Richardson, Arlan; Pérez, Viviana I.

    2009-01-01

    The oxidative stress theory of aging predicts that manipulations that alter oxidative stress/damage will alter aging. The gold standard for determining whether aging is altered is lifespan, i.e., does altering oxidative stress/damage change lifespan? Mice with genetic manipulations in the antioxidant defense system designed to directly address this prediction have, with few exceptions, shown no change in lifespan. However, when these transgenic/knockout mice are tested using models that devel...

  7. Does a 10-valent pneumococcal-Haemophilus influenzae protein D conjugate vaccine prevent respiratory exacerbations in children with recurrent protracted bacterial bronchitis, chronic suppurative lung disease and bronchiectasis: protocol for a randomised controlled trial

    Science.gov (United States)

    2013-01-01

    Background Recurrent protracted bacterial bronchitis (PBB), chronic suppurative lung disease (CSLD) and bronchiectasis are characterised by a chronic wet cough and are important causes of childhood respiratory morbidity globally. Haemophilus influenzae and Streptococcus pneumoniae are the most commonly associated pathogens. As respiratory exacerbations impair quality of life and may be associated with disease progression, we will determine if the novel 10-valent pneumococcal-Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) reduces exacerbations in these children. Methods A multi-centre, parallel group, double-blind, randomised controlled trial in tertiary paediatric centres from three Australian cities is planned. Two hundred six children aged 18 months to 14 years with recurrent PBB, CSLD or bronchiectasis will be randomised to receive either two doses of PHiD-CV or control meningococcal (ACYW135) conjugate vaccine 2 months apart and followed for 12 months after the second vaccine dose. Randomisation will be stratified by site, age (, nasopharyngeal and saliva swabs, and serum will be collected at baseline and at 2, 3, 8 and 14 months post-enrolment. Local and systemic reactions will be recorded on daily diaries for 7 and 30 days, respectively, following each vaccine dose and serious adverse events monitored throughout the trial. Fortnightly, parental contact will help record respiratory exacerbations. The primary outcome is the incidence of respiratory exacerbations in the 12 months following the second vaccine dose. Secondary outcomes include: nasopharyngeal carriage of H. influenzae and S. pneumoniae vaccine and vaccine- related serotypes; systemic and mucosal immune responses to H. influenzae proteins and S. pneumoniae vaccine and vaccine-related serotypes; impact upon lung function in children aged ≥6 years; and vaccine safety. Discussion As H. influenzae is the most common bacterial pathogen associated with these chronic respiratory diseases in

  8. Renal accumulation of pentosidine in non-diabetic proteinuria-induced renal damage in rats

    NARCIS (Netherlands)

    Waanders, F; Greven, WL; Baynes, JW; Thorpe, [No Value; Kramer, AB; Nagai, R; Sakata, N; van Goor, H; Navis, G

    2005-01-01

    Background. Advanced glycation end-products (AGEs) contribute to the pathogenesis of diabetic glomerulopathy. The role of AGEs in non-diabetic renal damage is not well characterized. First, we studied whether renal AGE accumulation occurs in non-diabetic proteinuria-induced renal damage and whether

  9. Damage spectra and damage maps for Romanian Vrancea earthquakes

    International Nuclear Information System (INIS)

    A number of frequently used damage indices are examined comparatively. Damage spectra are plotted and analysed for significant records of Romanian Vrancea earthquakes. Uniform damage spectra are developed as well, by computing yield strength demands for constant, specified values of the damage index. Spectral ordinates are mapped, in order to obtain the spatial distribution of damage potential and of yield strength demands. Results are discussed with reference to the available post-earthquake damage reports. (author)

  10. LSD and Genetic Damage

    Science.gov (United States)

    Dishotsky, Norman I.; And Others

    1971-01-01

    Reviews studies of the effects of lysergic acid diethylamide (LSD) on man and other organisms. Concludes that pure LSD injected in moderate doses does not cause chromosome or detectable genetic damage and is not a teratogen or carcinogen. (JM)

  11. Low concentration of arsenite exacerbates UVR-induced DNA strand breaks by inhibiting PARP-1 activity

    International Nuclear Information System (INIS)

    Epidemiological studies have associated arsenic exposure with many types of human cancers. Arsenic has also been shown to act as a co-carcinogen even at low concentrations. However, the precise mechanism of its co-carcinogenic action is unknown. Recent studies indicate that arsenic can interfere with DNA-repair processes. Poly(ADP-ribose) polymerase (PARP)-1 is a zinc-finger DNA-repair protein, which can promptly sense DNA strand breaks and initiate DNA-repair pathways. In the present study, we tested the hypothesis that low concentrations of arsenic could inhibit PAPR-1 activity and so exacerbate levels of ultraviolet radiation (UVR)-induced DNA strand breaks. HaCat cells were treated with arsenite and/or UVR, and then DNA strand breaks were assessed by comet assay. Low concentrations of arsenite (≤ 2 μM) alone did not induce significant DNA strand breaks, but greatly enhanced the DNA strand breaks induced by UVR. Further studies showed that 2 μM arsenite effectively inhibited PARP-1 activity. Zinc supplementation of arsenite-treated cells restored PARP-1 activity and significantly diminished the exacerbating effect of arsenite on UVR-induced DNA strand breaks. Importantly, neither arsenite treatment, nor zinc supplementation changed UVR-triggered reactive oxygen species (ROS) formation, suggesting that their effects upon UVR-induced DNA strand breaks are not through a direct free radical mechanism. Combination treatments of arsenite with PARP-1 inhibitor 3-aminobenzamide or PARP-1 siRNA demonstrate that PARP-1 is the target of arsenite. Together, these findings show that arsenite at low concentration exacerbates UVR-induced DNA strand breaks by inhibiting PARP-1 activity, which may represent an important mechanism underlying the co-carcinogenicity of arsenic

  12. Procalcitonin and other acute phase reactants in patients with chronic obstructive pulmonary disease exacerbation

    Directory of Open Access Journals (Sweden)

    Cemil Civelek

    2011-06-01

    Full Text Available The aim of this study was to investigate the correlation between procalcitonin and other acute phase reactants, and also analyze their relationship with clinical situation in chronic obstructive pulmonary disease (COPD acute exacerbations.Materials and methods: The study was made with 122 acute COPD exacerbated patients, who were admitted to emergency service. Patients with below 0.25 ng/ml PCT value included Group 1, and the patients with PCT values ≥ 0.25 ng/ml Group 2. Serum procalcitonin levels, erythrocyte sedimentation rate (ESR, C-reactive protein (CRP values and white blood cell (WBC counts were measured. Also, patients hospitalization time and mortality rates were recorded and compared with PCT.Results: Patients were divided in 3 groups according to their clinical diagnosis; Pneumonia (n=27, Mycoplasma-Chlamydia pneumonia (n=11 and the patients with only COPD exacerbation(n=84. Mean PCT values according to the groups were 9.47 ± 8.1 ng/ml, 0.41 ± 0.2 ng/ml, and 0.21 ± 0.05 ng/ml respectively. The relationship between PCT with CRP and white blood cell has been found between significiant (p=0.001, p=0.005 respectively, whereas the relationship between PCT and ESR was nonsignificant (p=0.55. Procalcitonin and CRP had a positive correlation with the hospitalization time (p=0.034, p=0.022 respectively. The mean ± standard error of PCT for the patients who died was 28.3 ± 27.5 ng/ml, and the difference between patients who died or were discharged was statistically significant (p= 0.012.Conclusion: PCT can be a useful indicator for morbidity and prognosis in COPD patients.

  13. A novel neutrophil derived inflammatory biomarker of pulmonary exacerbation in cystic fibrosis.

    LENUS (Irish Health Repository)

    2012-02-01

    BACKGROUND: The focus of this study was to characterize a novel biomarker for cystic fibrosis (CF) that could reflect exacerbations of the disease and could be useful for therapeutic stratification of patients, or for testing of potential drug treatments. This study focused exclusively on a protein complex containing alpha-1 antitrypsin and CD16b (AAT:CD16b) which is released into the bloodstream from membranes of pro-inflammatory primed neutrophils. METHODS: Neutrophil membrane expression and extracellular levels of AAT and CD16b were quantified by flow cytometry, Western blot analysis and by 2D-PAGE. Interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha) and AAT:CD16b complex were quantified in CF plasma (n=38), samples post antibiotic treatment for 14days (n=10), chronic obstructive pulmonary disease (n=10), AAT deficient (n=10) and healthy control (n=14) plasma samples by ELISA. RESULTS: Cell priming with IL-8 and TNF-alpha caused release of the AAT:CD16b complex from the neutrophil cell membrane. Circulating plasma levels of IL-8, TNF-alpha and AAT:CD16b complex were significantly higher in patients with CF than in the other patient groups or healthy controls (P<0.05). Antibiotic treatment of pulmonary exacerbation in patients with CF led to decreased plasma protein concentrations of AAT:CD16b complex with a significant correlation with improved FEV1 (r=0.81, P=0.003). CONCLUSION: The results of this study have shown that levels of AAT:CD16b complex present in plasma correlate to the inflammatory status of patients. The AAT:CD16b biomarker may become a useful addition to the clinical diagnosis of exacerbations in CF.

  14. Early-Life Intranasal Colonization with Nontypeable Haemophilus influenzae Exacerbates Juvenile Airway Disease in Mice.

    Science.gov (United States)

    McCann, Jessica R; Mason, Stanley N; Auten, Richard L; St Geme, Joseph W; Seed, Patrick C

    2016-07-01

    Accumulating evidence suggests a connection between asthma development and colonization with nontypeable Haemophilus influenzae (NTHi). Specifically, nasopharyngeal colonization of human infants with NTHi within 4 weeks of birth is associated with an increased risk of asthma development later in childhood. Monocytes derived from these infants have aberrant inflammatory responses to common upper respiratory bacterial antigens compared to those of cells derived from infants who were not colonized and do not go on to develop asthma symptoms in childhood. In this study, we hypothesized that early-life colonization with NTHi promotes immune system reprogramming and the development of atypical inflammatory responses. To address this hypothesis in a highly controlled model, we tested whether colonization of mice with NTHi on day of life 3 induced or exacerbated juvenile airway disease using an ovalbumin (OVA) allergy model of asthma. We found that animals that were colonized on day of life 3 and subjected to induction of allergy had exacerbated airway disease as juveniles, in which exacerbated airway disease was defined as increased cellular infiltration into the lung, increased amounts of inflammatory cytokines interleukin-5 (IL-5) and IL-13 in lung lavage fluid, decreased regulatory T cell-associated FOXP3 gene expression, and increased mucus production. We also found that colonization with NTHi amplified airway resistance in response to increasing doses of a bronchoconstrictor following OVA immunization and challenge. Together, the murine model provides evidence for early-life immune programming that precedes the development of juvenile airway disease and corroborates observations that have been made in human children. PMID:27113355

  15. Prulifloxacin vs Levofloxacin for Exacerbation of COPD after Failure of Other Antibiotics.

    Science.gov (United States)

    Giusti, Massimo; Blasi, Francesco; Iori, Ido; Mazzone, Antonino; Sgambato, Francesco; Politi, Cecilia; Colagrande, Paola; Casali, Annamaria; Valerio, Antonella; Gussoni, Gualberto; Bonizzoni, Erminio; Campanini, Mauro

    2016-10-01

    The chronic course and evolution of chronic obstructive pulmonary disease (COPD) is often characterized by periods of exacerbation of symptoms, which have a negative impact on the quality of life of patients, as well as on the evolution of COPD, and represent a significant cause of medical intervention and hospitalization. Very few data are available on the efficacy of rescue antibiotics in patients with acute exacerbation of COPD (AECOPD) unresponsive to previous treatment. The aim of this study was to evaluate the efficacy of two fluoroquinolones in AECOPD previously treated without success. The FADOI-FLOR study is a randomized, single-blind, non-inferiority comparison between levofloxacin and prulifloxacin. Primary end-point was "therapeutic success" at Day 10 of treatment, defined as disappearance of signs/symptoms or decrease of at least three points of a global score of symptomatology (maximum score = 15). 258 patients were enrolled (128 levofloxacin and 130 prulifloxacin), in 25 centers. A very high proportion of patients in the two groups had therapeutic success at Day-10 (levofloxacin 93.0% vs prulifloxacin 96.7%, population intention-to-treat; 94.6% vs 99.1%, population per-protocol). Earlier therapeutic success (within 7 days) was achieved in 32.0% and 36.2% of patients receiving levofloxacin or prulifloxacin, respectively. At 3-month follow-up, re-exacerbations occurred in 17.8% of patients treated with levofloxacin and 14.2% of those receiving prulifloxacin (p = 0.44). In conclusion, fluoroquinolones are very effective in the treatment of AECOPD resistant to other antibiotics. PMID:27027547

  16. Candidate markers associated with the probability of future pulmonary exacerbations in cystic fibrosis patients.

    Directory of Open Access Journals (Sweden)

    Gabriella Wojewodka

    Full Text Available INTRODUCTION: Pulmonary exacerbations (PEs cause significant morbidity and can severely impact disease progression in cystic fibrosis (CF lung disease, especially in patients who suffer from recurrent PEs. The assessments able to predict a future PE or a recurrent PE are limited. We hypothesized that combining clinical, molecular and patient reported data could identify patients who are at risk of PE. METHODS: We prospectively followed a cohort of 53 adult CF patients for 24 months. Baseline values for spirometry, clinical status using the Matouk Disease Score, quality of life (QOL, inflammatory markers (C-reactive protein (CRP, interleukins (IL-1β, -6, -8, -10, macrophage inflammatory protein (MIP-1β, tumor necrosis factor (TNF and vascular endothelial growth factor (VEGF, polyunsaturated fatty acids and lipid peroxidation in blood plasma were collected for all patients during periods of stable disease, and patients were monitored for PE requiring PO/IV antibiotic treatment. Additionally, we closely followed 13 patients during PEs collecting longitudinal data on changes in markers from baseline values. We assessed whether any markers were predictors of future PE at baseline and after antibiotic treatment. RESULTS: Out of 53 patients, 37 experienced PEs during our study period. At baseline, we found that low lung function, clinical scoring and QOL values were associated with increased risk of PE events. PEs were associated with increased inflammatory markers at Day 1, and these biomarkers improved with treatment. The imbalance in arachidonic acid and docosahexaenoic acid levels improved with treatment which coincided with reductions in lipid peroxidation. High levels of inflammatory markers CRP and IL-8 were associated with an early re-exacerbation. CONCLUSION: Our results demonstrate that worse clinical and QOL assessments during stable disease are potential markers associated with a higher risk of future PEs, while higher levels of

  17. Social isolation-induced increase in NMDA receptors in the hippocampus exacerbates emotional dysregulation in mice.

    Science.gov (United States)

    Chang, Chih-Hua; Hsiao, Ya-Hsin; Chen, Yu-Wen; Yu, Yang-Jung; Gean, Po-Wu

    2015-04-01

    Epidemiological studies have shown that early life adverse events have long-term effects on the susceptibility to subsequent stress exposure in adolescence, but the precise mechanism is unclear. In the present study, mice on postnatal day 21-28 were randomly assigned to either a group or isolated cages for 8 weeks. The socially isolated (SI) mice exhibited a higher level of spontaneous locomotor activity, a longer duration of immobility in the forced swimming test (FST), significantly less prepulse inhibition (PPI) and an increase in aggressive (but not attack) behavior. However, acute stress markedly exacerbated the attack counts of the SI mice but did not affect the group housing (GH) mice. SI mice exhibited higher synaptosomal NR2A and NR2B levels in the hippocampus as compared to the GH mice. Whole-cell patch clamp recordings of CA1 neurons in hippocampal slices showed that the SI mice exhibited a higher input-output relationship of NMDAR-EPSCs as compared to the GH mice. Application of the NR2B -specific antagonist ifenprodil produced a greater attenuating effect on NMDAR-EPSCs in slices from the SI mice. NMDAR EPSCs recorded from the SI mice had a slower deactivation kinetic. MK-801, CPP and ifenprodil, the NMDA antagonists, reversed acute stress-induced exaggeration of aggressive and depressive behaviors. Furthermore, acute stress-induced exacerbation of attack behavior in the SI mice was abolished after the knockdown of NR2B expression. These results suggest that social isolation-induced increased expression of NMDA receptors in the hippocampus involves stress exacerbation of aggressive behaviors. Amelioration of aggressive behaviors by NMDA antagonists may open a new avenue for the treatment of psychopathologies that involve outbursts of emotional aggression in neglected children. PMID:25348768

  18. Computerized lung sound analysis following clinical improvement of pulmonary edema due to congestive heart failure exacerbations

    Institute of Scientific and Technical Information of China (English)

    WANG Zhen; XIONG Ying-xia

    2010-01-01

    Background Although acute congestive heart failure (CHF) patients typically present with abnormal auscultatory findings on lung examination, lung sounds are not normally subjected to rigorous analysis. The goals of this study were to use a computerized analytic acoustic tool to evaluate lung sound patterns in CHF patients during acute exacerbation and after clinical improvement and to compare CHF profiles with those of normal individuals.Methods Lung sounds throughout the respiratory cycle was captured using a computerized acoustic-based imaging technique. Thirty-two consecutive CHF patients were imaged at the time of presentation to the emergency department and after clinical improvement. Digital images were created, geographical area of the images and lung sound patterns were quantitatively analyzed.Results The geographical areas of the vibration energy image of acute CHF patients without and with radiographically evident pulmonary edema were (67.9±4.7) and (60.3±3.5) kilo-pixels, respectively (P <0.05). In CHF patients without and with radiographically evident pulmonary edema (REPE), after clinical improvement the geographical area of vibration energy image of lung sound increased to (74.5±4.4) and (73.9±3.9) kilo-pixels (P <0.05), respectively. Vibration energy decreased in CHF patients with REPE following clinical improvement by an average of (85±19)% (P <0.01). Conclusions With clinical improvement of acute CHF exacerbations, there was more homogenous distribution of lung vibration energy, as demonstrated by the increased geographical area of the vibration energy image. Lung sound analysis may be useful to track in acute CHF exacerbations.

  19. Lights and shadows of non-invasive mechanical ventilation for chronic obstructive pulmonary disease (COPD exacerbations

    Directory of Open Access Journals (Sweden)

    Jose Luis Lopez-Campos

    2015-01-01

    Full Text Available Despite the overwhelming evidence justifying the use of non-invasive ventilation (NIV for providing ventilatory support in chronic obstructive pulmonary disease (COPD exacerbations, recent studies demonstrated that its application in real-life settings remains suboptimal. European clinical audits have shown that 1 NIV is not invariably available, 2 its availability depends on countries and hospital sizes, and 3 numerous centers declare their inability to provide NIV to all of the eligible patients presenting throughout the year. Even with an established indication, the use of NIV in acute respiratory failure due to COPD exacerbations faces important challenges. First, the location and personnel using NIV should be carefully selected. Second, the use of NIV is not straightforward despite the availability of technologically advanced ventilators. Third, NIV therapy of critically ill patients requires a thorough knowledge of both respiratory physiology and existing ventilatory devices. Accordingly, an optimal team-training experience, the careful selection of patients, and special attention to the selection of devices are critical for optimizing NIV outcomes. Additionally, when applied, NIV should be closely monitored, and endotracheal intubation should be promptly available in the case of failure. Another topic that merits careful consideration is the use of NIV in the elderly. This patient population is particularly fragile, with several physiological and social characteristics requiring specific attention in relation to NIV. Several other novel indications should also be critically examined, including the use of NIV during fiberoptic bronchoscopy or transesophageal echocardiography, as well as in interventional cardiology and pulmonology. The present narrative review aims to provide updated information on the use of NIV in acute settings to improve the clinical outcomes of patients hospitalized for COPD exacerbations.

  20. Exacerbation of allergic inflammation in mice exposed to diesel exhaust particles prior to viral infection

    Directory of Open Access Journals (Sweden)

    Chason Kelly D

    2009-08-01

    Full Text Available Abstract Background Viral infections and exposure to oxidant air pollutants are two of the most important inducers of asthma exacerbation. Our previous studies have demonstrated that exposure to diesel exhaust increases the susceptibility to influenza virus infections both in epithelial cells in vitro and in mice in vivo. Therefore, we examined whether in the setting of allergic asthma, exposure to oxidant air pollutants enhances the susceptibility to respiratory virus infections, which in turn leads to increased virus-induced exacerbation of asthma. Ovalbumin-sensitized (OVA male C57BL/6 mice were instilled with diesel exhaust particles (DEP or saline and 24 hours later infected with influenza A/PR/8. Animals were sacrificed 24 hours post-infection and analyzed for markers of lung injury, allergic inflammation, and pro-inflammatory cytokine production. Results Exposure to DEP or infection with influenza alone had no significant effects on markers of injury or allergic inflammation. However, OVA-sensitized mice that were exposed to DEP and subsequently infected with influenza showed increased levels of eosinophils in lung lavage and tissue. In addition Th2-type cytokines, such as IL-4 and IL-13, and markers of eosinophil chemotaxis, such as CCL11 and CCR3, were increased in OVA-sensitized mice exposed to DEP prior to infection with influenza. These mice also showed increased levels of IL-1α, but not IL-10, RANTES, and MCP-1 in lung homogenates. Conclusion These data suggest that in the setting of allergic asthma, exposure to diesel exhaust could enhance virus-induced exacerbation of allergic inflammation.