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Sample records for ageing exacerbates damage

  1. Ageing exacerbates damage of systemic and salivary neutrophils from patients presenting Candida-related denture stomatitis

    Directory of Open Access Journals (Sweden)

    Porto Vinicius

    2009-03-01

    Full Text Available Abstract Background Ageing leads to a decline in the function of the immune system, increasing the body's susceptibility to infections through the impairment of T-cells, macrophages, neutrophils and dendritic cells Denture stomatitis is a primary oral disease affecting elderly denture wearers. The major etiologic factor involved in this pathology is the infection by Candida albicans, an opportunistic pathogen that causes local and disseminated diseases in immunosuppressed humans. Neutrophils play a critical role in the immune response against C. albicans and are continually present in the salivary fluid and in the blood. The aim of this study was to determine ageing-related changes in salivary and blood neutrophils and their potential implications in Candida-related denture stomatitis. Results Our results showed a lower number of neutrophils in the saliva from patients presenting Candida-related denture stomatitis in comparison to their matched controls. Furthermore, fewer neutrophils were isolated from the saliva of aged control individuals in comparison to matched younger subjects. CXCR1, CD62L and CD11b expression were significantly greater on systemic neutrophils from younger control individuals. Elderly individuals showed more apoptotic salivary neutrophils and lower GM-CSF levels than younger ones, regardless of the occurrence of Candida infection. On the other hand, CXCL-8 concentrations were higher in the saliva from elderly individuals. Besides, TNF-α was detected at elevated levels in the saliva from infected elderly subjects. Salivary neutrophils from elderly and young patients presented impaired phagocytic activity against C. albicans. However, just systemic neutrophils from elderly showed decreased phagocytosis when compared to the younger ones, regardless of the occurrence of infection. In addition, neutrophils from aged individuals and young patients presented low fungicidal activity. Conclusion The data suggests that the Candida

  2. 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...

  3. 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

    could predict an asthma exacerbation in children 2 to 5 years of age. METHODS: Post hoc analyses were conducted on data collected in a study of 689 patients 2 to 5 years of age with asthma symptoms, randomly assigned to montelukast, 4 mg, or placebo daily for 12 weeks. During the study, 196 patients had...

  4. Muscimol microinjection into cerebellar fastigial nucleus exacerbates stress-induced gastric mucosal damage in rats

    Institute of Scientific and Technical Information of China (English)

    Jin-zhou ZHU; Su-juan FEI; Jian-fu ZHANG; Sheng-ping ZHU; Zhang-bo LIU; Ting-ting LI; Xiao QIAO

    2013-01-01

    Aim: To investigate the effects of microinjection of the GABAA receptor agonist muscimol into cerebellar fastigial nucleus (FN) on stressinduced gastric mucosal damage and the underlying mechanism in rats.Methods: Stress-induced gastric mucosal damage was induced in adult male SD rats by restraining and immersing them in cold water for 3 h.GABAA receptor agonist or antagonist was microinjected into the lateral FN.The decussation of superior cerebellar peduncle (DSCP) was electrically destroyed and the lateral hypothalamic area (LHA) was chemically ablated by microinjection of kainic acid.The pathological changes in the gastric mucosa were evaluated using TUNEL staining,immunohistochemistry staining and Western blotting.Results: Microinjection of muscimol (1.25,2.5,and 5.0 μg) into FN significantly exacerbated the stress-induced gastric mucosal damage in a dose-dependent manner,whereas microinjection of GABAA receptor antagonist bicuculline attenuated the damage.The intensifying effect of muscimol on gastric mucosal damage was abolished by electrical lesion of DSCP or chemical ablation of LHA performed 3 d before microinjection of muscimol.Microinjection of muscimol markedly increased the discharge frequency of the greater splanchnic nerve,significantly increased the gastric acid volume and acidity,and further reduced the gastric mucosal blood flow.In the gastric mucosa,further reduced proliferation cells,enhanced apoptosis,and decreased anti-oxidant levels were observed following microinjection of muscimol.Conclusion: Cerebellar FN participates in the regulation of stress-induced gastric mucosal damage,and cerebello-hypothalamic circuits contribute to the process.

  5. 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...

  6. 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…

  7. 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

    Science.gov (United States)

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

    2014-01-01

    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 inflammation and blood–brain barrier disruption, as indicated by the increased circulating levels of proinflammatory cytokines and increased presence of extravasated immunoglobulin G in the hippocampus, respectively. Obesity-induced blood–brain barrier damage was associated with microglia activation, upregulation of activating Fc-gamma receptors and proinflammatory cytokines, and increased oxidative stress. Treatment of cultured primary microglia with sera derived from aged obese mice resulted in significantly more pronounced microglia activation and oxidative stress, as compared with treatment with young sera. Serum-induced activation and oxidative stress were also exacerbated in primary microglia derived from aged animals. Hippocampal expression of genes involved in regulation of the cellular amyloid precursor protein–dependent signaling pathways, beta-amyloid generation, and the pathogenesis of tauopathy were largely unaffected by obesity in aged mice. Collectively, obesity in aging is associated with a heightened state of systemic inflammation, which exacerbates blood–brain barrier disruption. The resulting neuroinflammation and oxidative stress in the mouse hippocampus likely contribute to the significant cognitive decline observed in aged obese animals. PMID:24269929

  8. 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.

    Science.gov (United States)

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

    2014-10-01

    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 inflammation and blood-brain barrier disruption, as indicated by the increased circulating levels of proinflammatory cytokines and increased presence of extravasated immunoglobulin G in the hippocampus, respectively. Obesity-induced blood-brain barrier damage was associated with microglia activation, upregulation of activating Fc-gamma receptors and proinflammatory cytokines, and increased oxidative stress. Treatment of cultured primary microglia with sera derived from aged obese mice resulted in significantly more pronounced microglia activation and oxidative stress, as compared with treatment with young sera. Serum-induced activation and oxidative stress were also exacerbated in primary microglia derived from aged animals. Hippocampal expression of genes involved in regulation of the cellular amyloid precursor protein-dependent signaling pathways, beta-amyloid generation, and the pathogenesis of tauopathy were largely unaffected by obesity in aged mice. Collectively, obesity in aging is associated with a heightened state of systemic inflammation, which exacerbates blood-brain barrier disruption. The resulting neuroinflammation and oxidative stress in the mouse hippocampus likely contribute to the significant cognitive decline observed in aged obese animals.

  9. Cross-generational trans fat intake exacerbates UV radiation-induced damage in rat skin.

    Science.gov (United States)

    Barcelos, R C S; Vey, L T; Segat, H J; Roversi, K; Roversi, Kr; Dias, V T; Trevizol, F; Kuhn, F T; Dolci, G S; Pase, C S; Piccolo, J; Veit, J C; Emanuelli, T; Luz, S C A; Bürger, M E

    2014-07-01

    We evaluated the influence of dietary fats on ultraviolet radiation (UVR)-induced oxidative damage in skin of rats. Animals from two consecutive generations born of dams supplemented with fats during pregnancy and breastfeeding were maintained in the same supplementation: soybean-oil (SO, rich in n-6 FA, control group), fish-oil (FO, rich in n-3 FA) or hydrogenated-vegetable-fat (HVF, rich in TFA). At 90 days of age, half the animals from the 2nd generation were exposed to UVR (0.25 J/cm(2)) 3×/week for 12 weeks. The FO group presented higher incorporation of n-3 FA in dorsal skin, while the HVF group incorporated TFA. Biochemical changes per se were observed in skin of the HVF group: greater generation of reactive oxygen species (ROS), lower mitochondrial integrity and increased Na(+)K(+)-ATPase activity. UVR exposure increased skin wrinkles scores and ROS generation and decreased mitochondrial integrity and reduced-glutathione levels in the HVF group. In FO, UVR exposure was associated with smaller skin thickness and reduced levels of protein-carbonyl, together with increased catalase activity and preserved Na(+)K(+)-ATPase function. In conclusion, while FO may be protective, trans fat may be harmful to skin health by making it more vulnerable to UVR injury and thus more prone to develop photoaging and skin cancer.

  10. 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 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 use 1 day before...

  11. 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.

  12. 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...... evidence for aging-associated accumulation of oxidatively damaged DNA in organs with limited cell proliferation....

  13. Loss of Sodium/Hydrogen Exchanger NHA2 Exacerbates Obesity- and Aging-Induced Glucose Intolerance in Mice

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    Deisl, Christine; Anderegg, Manuel; Albano, Giuseppe; Lüscher, Benjamin P.; Cerny, David; Soria, Rodrigo; Bouillet, Elisa; Rimoldi, Stefano; Scherrer, Urs

    2016-01-01

    We previously demonstrated that the sodium/hydrogen exchanger NHA2, also known as NHEDC2 or SLC9B2, is critical for insulin secretion by β–cells. To gain more insights into the role of NHA2 on systemic glucose homeostasis, we studied the impact of loss of NHA2 during the physiological aging process and in the setting of diet-induced obesity. While glucose tolerance was normal at 2 months of age, NHA2 KO mice displayed a significant glucose intolerance at 5 and 12 months of age, respectively. An obesogenic high fat diet further exacerbated the glucose intolerance of NHA2 KO mice. Insulin levels remained similar in NHA2 KO and WT mice during aging and high fat diet, but fasting insulin/glucose ratios were significantly lower in NHA2 KO mice. Peripheral insulin sensitivity, measured by insulin tolerance tests and hyperinsulinemic euglycemic clamps, was unaffected by loss of NHA2 during aging and high fat diet. High fat diet diminished insulin secretion capacity in both WT and NHA2 KO islets and reduced expression of NHA2 in WT islets. In contrast, aging was characterized by a gradual increase of NHA2 expression in islets, paralleled by an increasing difference in insulin secretion between WT and NHA2 KO islets. In summary, our results demonstrate that loss of the sodium/hydrogen exchanger NHA2 exacerbates obesity- and aging-induced glucose intolerance in mice. Furthermore, our data reveal a close link between NHA2 expression and insulin secretion capacity in islets. PMID:27685945

  14. Increased molecular damage and heterogeneity as the basis of aging.

    Science.gov (United States)

    Rattan, Suresh I S

    2008-03-01

    Aging at the molecular level is characterized by the progressive accumulation of molecular damage. The sources of damage act randomly through environmental and metabolically generated free radicals, through spontaneous errors in biochemical reactions, and through nutritional components. However, damage to a macromolecule may depend on its structure, localization and interactions with other macromolecules. Damage to the maintenance and repair pathways comprising homeodynamic machinery leads to age-related failure of homeodynamics, increased molecular heterogeneity, altered cellular functioning, reduced stress tolerance, diseases and ultimate death. Novel approaches for testing and developing effective means of intervention, prevention and modulation of aging involve means to minimize the occurrence and accumulation of molecular damage. Mild stress-induced hormesis by physical, biological and nutritional methods, including hormetins, represents a promising strategy for achieving healthy aging and for preventing age-related diseases.

  15. 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…

  16. 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...

  17. 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 ...

  18. Nuclear DNA damage signalling to mitochondria in ageing.

    Science.gov (United States)

    Fang, Evandro Fei; Scheibye-Knudsen, Morten; Chua, Katrin F; Mattson, Mark P; Croteau, Deborah L; Bohr, Vilhelm A

    2016-05-01

    Mitochondrial dysfunction is a hallmark of ageing, and mitochondrial maintenance may lead to increased healthspan. Emerging evidence suggests a crucial role for signalling from the nucleus to mitochondria (NM signalling) in regulating mitochondrial function and ageing. An important initiator of NM signalling is nuclear DNA damage, which accumulates with age and may contribute to the development of age-associated diseases. DNA damage-dependent NM signalling constitutes a network that includes nuclear sirtuins and controls genomic stability and mitochondrial integrity. Pharmacological modulation of NM signalling is a promising novel approach for the prevention and treatment of age-associated diseases.

  19. 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

  20. 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.

  1. Cigarette smoking exacerbates the adverse effects of age and metabolic syndrome on subclinical atherosclerosis: the Bogalusa Heart Study.

    Directory of Open Access Journals (Sweden)

    Shengxu Li

    Full Text Available Age and metabolic syndrome are major risk factors for atherosclerosis. However, limited information is available regarding whether cigarette smoking, another major, modifiable risk factor, has synergistic effects with age and metabolic syndrome on subclinical atherosclerosis, particularly in young adults. This aspect was examined in 1,051 adults (747 whites and 304 blacks; aged 24-43 years from the Bogalusa Heart Study. General linear models were used to examine the effects of cigarette smoking and its interactive effects with age and metabolic syndrome on carotid intima-media thickness (CIMT. After adjusting for age, race, and sex, current smokers had lower BMI (mean ± SE: 27.4 ± 0.4, 29.3 ± 0.5, and 29.9 ± 0.3 kg/m2 in current, former, and never smokers, respectively; p<0.0001 and lower levels of fasting glucose (82.8 ± 0.9, 89.5 ± 2.3, and 87.1 ± 1.1 mg/dL, respectively; p = 0.001 and insulin (10.6 ± 0.4, 14.2 ± 1.0, 13.6 ± 0. 6 µU/ml, respectively; p<0.0001. Despite being lean and having favorable levels of glucose and insulin, current smokers had greater CIMT (0.850 ± 0.012, 0.808 ± 0.011, and 0.801 ± 0.006 mm, respectively; p = 0.0004. Importantly, cigarette smoking showed significant interactions with age and metabolic syndrome on CIMT: Age-related change in CIMT in current smokers was significantly greater (0.013 ± 0.002 mm/year than in nonsmokers (former and never smokers combined (0.008 ± 0.001 mm/year (p for interaction = 0.005; the difference in CIMT between those with and without metabolic syndrome was significantly greater in current smokers (0.154 ± 0.030 mm, p<0.0001 than in nonsmokers (0.031 ± 0.014 mm, p = 0.03 (p for interaction<0.0001. In conclusion, cigarette smoking significantly exacerbates the adverse effects of age and metabolic syndrome on subclinical atherosclerosis in young adults, which underscores the importance of prevention and cessation of cigarette smoking behavior in the young.

  2. Impact of genomic damage and ageing on stem cell function

    NARCIS (Netherlands)

    Behrens, A.; Deursen, J.M. van; Rudolph, K.L.; Schumacher, B.

    2014-01-01

    Impairment of stem cell function contributes to the progressive deterioration of tissue maintenance and repair with ageing. Evidence is mounting that age-dependent accumulation of DNA damage in both stem cells and cells that comprise the stem cell microenvironment are partly responsible for stem cel

  3. 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...

  4. Salt crystallization damage: how realistic are existing ageing tests

    NARCIS (Netherlands)

    Lubelli, B.A.; Hees, R.P.J. van; Nijland, T.G.

    2014-01-01

    Salt crystallization is a major cause of damage in porous building materials (figure l). Notwithstanding the extensive research in this held, the complexity of the problem has hindered the use of mathematical models for forecasting ageing due to salt crystallization. Nowadays, the resistance of mate

  5. Bone marrow failure in Fanconi anemia is triggered by an exacerbated p53/p21 DNA damage response that impairs hematopoietic stem and progenitor cells.

    Science.gov (United States)

    Ceccaldi, Raphael; Parmar, Kalindi; Mouly, Enguerran; Delord, Marc; Kim, Jung Min; Regairaz, Marie; Pla, Marika; Vasquez, Nadia; Zhang, Qing-Shuo; Pondarre, Corinne; Peffault de Latour, Régis; Gluckman, Eliane; Cavazzana-Calvo, Marina; Leblanc, Thierry; Larghero, Jérôme; Grompe, Markus; Socié, Gérard; D'Andrea, Alan D; Soulier, Jean

    2012-07-01

    Fanconi anemia (FA) is an inherited DNA repair deficiency syndrome. FA patients undergo progressive bone marrow failure (BMF) during childhood, which frequently requires allogeneic hematopoietic stem cell transplantation. The pathogenesis of this BMF has been elusive to date. Here we found that FA patients exhibit a profound defect in hematopoietic stem and progenitor cells (HSPCs) that is present before the onset of clinical BMF. In response to replicative stress and unresolved DNA damage, p53 is hyperactivated in FA cells and triggers a late p21(Cdkn1a)-dependent G0/G1 cell-cycle arrest. Knockdown of p53 rescued the HSPC defects observed in several in vitro and in vivo models, including human FA or FA-like cells. Taken together, our results identify an exacerbated p53/p21 "physiological" response to cellular stress and DNA damage accumulation as a central mechanism for progressive HSPC elimination in FA patients, and have implications for clinical care.

  6. 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

  7. Enhanced Endothelin-1 Mediated Vasoconstriction of the Ophthalmic Artery May Exacerbate Retinal Damage after Transient Global Cerebral Ischemia in Rat

    DEFF Research Database (Denmark)

    Blixt, Frank W; Johansson, Sara Ellinor; Johnson, Leif;

    2016-01-01

    Cerebral vasculature is often the target of stroke studies. However, the vasculature supplying the eye might also be affected by ischemia. The aim of the present study was to investigate if the transient global cerebral ischemia (GCI) enhances vascular effect of endothelin-1 (ET-1) and 5...... of ET-1 mediated vasoconstriction at 48 hours post ischemia. The retina did not exhibit any morphological changes throughout the study. However, we found an increase of GFAP and vimentin expression at 72 hours and 7 days after ischemia, indicating Müller cell mediated gliosis. ERG revealed significantly...... damage after ischemia as illustrated by the decreased retinal function and Müller cell activation. The ophthalmic artery and ET-1 mediated vasoconstriction may be a valid and novel therapeutic target after longer periods of ischemic insults....

  8. Long-term moderate alcohol consumption does not exacerbate age-related cognitive decline in healthy, community-dwelling older adults

    Directory of Open Access Journals (Sweden)

    Malaak Nasser Moussa

    2015-01-01

    Full Text Available Recent census data has found that roughly 40% of adults 65 years and older not only consume alcohol but also drink more of it than previous generations. Older drinkers are more vulnerable than younger counterparts to the psychoactive effects of alcohol due to natural biological changes that occur with aging. This study was specifically designed to measure the effect of long-term moderate alcohol consumption on cognitive health in older adult drinkers. An extensive battery of validated tests commonly used in aging and substance use literature was used to measure performance in specific cognitive domains, including working memory and attention. An age (young, old * alcohol consumption (light, moderate factorial study design was used to evaluate the main effects of age and alcohol consumption on cognitive performance. The focus of the study was then limited to light and moderate older drinkers, and whether or not long–term moderate alcohol consumption exacerbated age-related cognitive decline. No evidence was found to support the idea that long-term moderate alcohol consumption in older adults exacerbates age-related cognitive decline. Findings were specific to healthy community dwelling social drinkers in older age and they should not be generalized to individuals with other consumption patterns, like heavy drinkers, binge drinkers or ex-drinkers.

  9. 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.

  10. 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

  11. 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

  12. 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.

  13. NaDC3 Induces Premature Cellular Senescence by Promoting Transport of Krebs Cycle Intermediates, Increasing NADH, and Exacerbating Oxidative Damage.

    Science.gov (United States)

    Ma, Yuxiang; Bai, Xue-Yuan; Du, Xuan; Fu, Bo; Chen, Xiangmei

    2016-01-01

    High-affinity sodium-dependent dicarboxylate cotransporter 3 (NaDC3) is a key metabolism-regulating membrane protein responsible for transport of Krebs cycle intermediates. NaDC3 is upregulated as organs age, but knowledge regarding the underlying mechanisms by which NaDC3 modulates mammalian aging is limited. In this study, we showed that NaDC3 overexpression accelerated cellular senescence in young human diploid cells (MRC-5 and WI-38) and primary renal tubular cells, leading to cell cycle arrest in G1 phase and increased expression of senescent biomarkers, senescence-associated β-galactosidase and p16. Intracellular levels of reactive oxygen species, 8-hydroxy-2'-deoxyguanosine, malondialdehyde, and carbonyl were significantly enhanced, and activities of respiratory complexes I and III and ATP level were significantly decreased in NaDC3-infected cells. Stressful premature senescent phenotypes induced by NaDC3 were markedly ameliorated via treatment with the antioxidants Tiron and Tempol. High expression of NaDC3 caused a prominent increase in intracellular levels of Krebs cycle intermediates and NADH. Exogenous NADH and NAD(+) may aggravate and attenuate the aging phenotypes induced by NaDC3, respectively. These results suggest that NaDC3 can induce premature cellular senescence by promoting the transport of Krebs cycle intermediates, increasing generation of NADH and reactive oxygen species and leading to oxidative damage. Our results clarify the aging signaling pathway regulated by NaDC3.

  14. 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...

  15. Micro-geographical variation in exposure to Schistosoma mansoni and malaria, and exacerbation of splenomegaly in Kenyan school-aged children

    Directory of Open Access Journals (Sweden)

    Kimani Gachuhi

    2004-05-01

    . mansoni and malaria infections can be exploited to investigate the chronic impact of these two infections. These results provide firm evidence that relatively high exposure to both infections exacerbates splenomegaly even outside the malaria transmission season. Major implications include assessing the burden of infection in school age-children.

  16. 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].

  17. 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

    Aging is associated with oxidative stress-generated damage to DNA and this could be related to metabolic disturbances. This study investigated the association between levels of oxidatively damaged DNA in peripheral blood mononuclear cells (PBMCs) and metabolic risk factors in 1,019 subjects, aged......, 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...... metabolic syndrome criteria. In summary, positive associations between age and levels of oxidatively damaged DNA appeared mediated by age-related increases in metabolic risk factors....

  18. How does tree age influence damage and recovery in forests impacted by freezing rain and snow?

    Science.gov (United States)

    Zhu, LiRong; Zhou, Ting; Chen, BaoMing; Peng, ShaoLin

    2015-05-01

    The response and recovery mechanisms of forests to damage from freezing rain and snow events are a key topic in forest research and management. However, the relationship between the degree of damage and tree age, i.e., whether seedlings, young trees, or adult trees are most vulnerable, remains unclear and is rarely reported. We investigated the effect of tree age on the degrees of vegetation damage and subsequent recovery in three subtropical forest types-coniferous, mixed, and broad-leaved-in the Tianjing Mountains, South China, after a series of rare icy rain and freezing snow events in 2008. The results showed that damage and recovery rates were both dependent on tree age, with the proportion of damaged vegetation increasing with age (estimated by diameter at breast height, DBH) in all three forest types and gradually plateauing. Significant variation occurred among forest types. Young trees in the coniferous forest were more vulnerable than those in the broad-leaved forest. The type of damage also varied with tree age in different ways in the three forest types. The proportion of young seedlings that were uprooted (the most severe type of damage) was highest in the coniferous forest. In the mixed forest, young trees were significantly more likely to be uprooted than seedlings and adult trees, while in the broad-leaved forest, the proportion of uprooted adult trees was significantly higher than that of seedlings and young trees. There were also differences among forest types in how tree age affected damage recovery. In the coniferous forest, the recovery rate of trees with broken trunks or crowns (DBH > 2.5 cm) increased with tree age. However, in the mixed and broad-leaved forests, no obvious correlation between the recovery rate of trees with broken trunks or crowns and tree age was observed. Trees with severe root damage did not recover; they were uprooted and died. In these forests, vegetation damage and recovery showed tree age dependencies, which varied

  19. 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.

  20. Acute exacerbations of fibrotic interstitial lung disease.

    Science.gov (United States)

    Churg, Andrew; Wright, Joanne L; Tazelaar, Henry D

    2011-03-01

    An acute exacerbation is the development of acute lung injury, usually resulting in acute respiratory distress syndrome, in a patient with a pre-existing fibrosing interstitial pneumonia. By definition, acute exacerbations are not caused by infection, heart failure, aspiration or drug reaction. Most patients with acute exacerbations have underlying usual interstitial pneumonia, either idiopathic or in association with a connective tissue disease, but the same process has been reported in patients with fibrotic non-specific interstitial pneumonia, fibrotic hypersensitivity pneumonitis, desquamative interstitial pneumonia and asbestosis. Occasionally an acute exacerbation is the initial manifestation of underlying interstitial lung disease. On biopsy, acute exacerbations appear as diffuse alveolar damage or bronchiolitis obliterans organizing pneumonia (BOOP) superimposed upon the fibrosing interstitial pneumonia. Biopsies may be extremely confusing, because the acute injury pattern can completely obscure the underlying disease; a useful clue is that diffuse alveolar damage and organizing pneumonia should not be associated with old dense fibrosis and peripheral honeycomb change. Consultation with radiology can also be extremely helpful, because the fibrosing disease may be evident on old or concurrent computed tomography scans. The aetiology of acute exacerbations is unknown, and the prognosis is poor; however, some patients survive with high-dose steroid therapy.

  1. 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.

  2. 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...

  3. Targeting the age-related occurrence, removal, and accumulation of molecular damage by hormesis.

    Science.gov (United States)

    Rattan, Suresh I S

    2010-06-01

    Strategies for testing and developing effective means of intervention, prevention, and modulation of aging incorporate means to minimize the occurrence and accumulation of molecular damage, to reduce molecular heterogeneity, and to evaluate the relevance of the type and extent of damage with respect to its role in aging and age-related diseases. One such approach is that of mild stress-induced hormesis, which stimulates maintenance and repair systems and strengthens the homeodynamic space of cells and organisms. Hormesis through mild heat shock, natural and synthetic hormetins, and other stressors brings about several antiaging effects in human fibroblasts, keratinocytes, and telomerase-immortalized bone marrow stem cells. Depending on the cell type, these antiaging hormetic effects include extension of replicative life span, enhanced proteasomal activities, increased chaperone levels, and improved wound healing, angiogenesis, and differentiation. The main molecular pathways for achieving such hormetic effects are through targeting the processes for the repair and removal of molecular damage, which can slow aging.

  4. 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

  5. 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...

  6. 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...

  7. Acute exacerbation of COPD.

    Science.gov (United States)

    Ko, Fanny W; Chan, Ka Pang; Hui, David S; Goddard, John R; Shaw, Janet G; Reid, David W; Yang, Ian A

    2016-10-01

    The literature of acute exacerbation of chronic obstructive pulmonary disease (COPD) is fast expanding. This review focuses on several aspects of acute exacerbation of COPD (AECOPD) including epidemiology, diagnosis and management. COPD poses a major health and economic burden in the Asia-Pacific region, as it does worldwide. Triggering factors of AECOPD include infectious (bacteria and viruses) and environmental (air pollution and meteorological effect) factors. Disruption in the dynamic balance between the 'pathogens' (viral and bacterial) and the normal bacterial communities that constitute the lung microbiome likely contributes to the risk of exacerbations. The diagnostic approach to AECOPD varies based on the clinical setting and severity of the exacerbation. After history and examination, a number of investigations may be useful, including oximetry, sputum culture, chest X-ray and blood tests for inflammatory markers. Arterial blood gases should be considered in severe exacerbations, to characterize respiratory failure. Depending on the severity, the acute management of AECOPD involves use of bronchodilators, steroids, antibiotics, oxygen and noninvasive ventilation. Hospitalization may be required, for severe exacerbations. Nonpharmacological interventions including disease-specific self-management, pulmonary rehabilitation, early medical follow-up, home visits by respiratory health workers, integrated programmes and telehealth-assisted hospital at home have been studied during hospitalization and shortly after discharge in patients who have had a recent AECOPD. Pharmacological approaches to reducing risk of future exacerbations include long-acting bronchodilators, inhaled steroids, mucolytics, vaccinations and long-term macrolides. Further studies are needed to assess the cost-effectiveness of these interventions in preventing COPD exacerbations.

  8. 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 ...

  9. Detecting exacerbations using the Clinical COPD Questionnaire

    Directory of Open Access Journals (Sweden)

    Trappenburg Jaap CA

    2010-09-01

    Full Text Available Abstract Background Early treatment of COPD exacerbations has shown to be important. Despite a non-negligible negative impact on health related quality of life, a large proportion of these episodes is not reported (no change in treatment. Little is known whether (low burden strategies are able to capture these unreported exacerbations. Methods The Clinical COPD Questionnaire (CCQ is a short questionnaire with great evaluative properties in measuring health status. The current explorative study evaluates the discriminative properties of weekly CCQ assessment in detecting exacerbations. Results In a multicentre prospective cohort study, 121 patients, age 67.4 ± 10.5 years, FEV1 47.7 ± 18.5% pred were followed for 6 weeks by daily diary card recording and weekly CCQ assessment. Weeks were retrospectively labeled as stable or exacerbation (onset weeks using the Anthonisen symptom diary-card algorithm. Change in CCQ total scores are significantly higher in exacerbation-onset weeks, 0.35 ± 0.69 compared to -0.04 ± 0.37 in stable weeks (p Conclusions Weekly CCQ assessment is a promising, low burden method to detect unreported exacerbations. Further research is needed to validate discriminative performance and practical implications of the CCQ in detecting exacerbations in daily care.

  10. 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

  11. 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.

  12. 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.

  13. 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...

  14. 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 DNA...... recently, BER was shown to also exist in the mitochondria. Here, we review the association of BER of oxidative DNA damage with aging, cancer and other diseases....... readily, generating a variety of DNA lesions, such as oxidized bases and strand breaks. If not properly removed, DNA damage can be potentially devastating to normal cell physiology, leading to mutagenesis and/or cell death, especially in the case of cytotoxic lesions that block the progression of DNA...

  15. Mitochondrial ROS regulate oxidative damage and mitophagy but not age-related muscle fiber atrophy

    Science.gov (United States)

    Sakellariou, Giorgos K.; Pearson, Timothy; Lightfoot, Adam P.; Nye, Gareth A.; Wells, Nicola; Giakoumaki, Ifigeneia I.; Vasilaki, Aphrodite; Griffiths, Richard D.; Jackson, Malcolm J.; McArdle, Anne

    2016-01-01

    Age-related loss of skeletal muscle mass and function is a major contributor to morbidity and has a profound effect on the quality of life of older people. The potential role of age-dependent mitochondrial dysfunction and cumulative oxidative stress as the underlying cause of muscle aging remains a controversial topic. Here we show that the pharmacological attenuation of age-related mitochondrial redox changes in muscle with SS31 is associated with some improvements in oxidative damage and mitophagy in muscles of old mice. However, this treatment failed to rescue the age-related muscle fiber atrophy associated with muscle atrophy and weakness. Collectively, these data imply that the muscle mitochondrial redox environment is not a key regulator of muscle fiber atrophy during sarcopenia but may play a key role in the decline of mitochondrial organelle integrity that occurs with muscle aging. PMID:27681159

  16. 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.

  17. 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.

  18. 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.

  19. 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...

  20. 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

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

    Directory of Open Access Journals (Sweden)

    Kristoffer Svensson

    Full Text Available 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.

  2. 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

  3. 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...

  4. 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

  5. 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.

  6. 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.

  7. From DNA damage to functional changes of the trabecular meshwork in aging and glaucoma.

    Science.gov (United States)

    Saccà, Sergio Claudio; Gandolfi, Stefano; Bagnis, Alessandro; Manni, Gianluca; Damonte, Gianluca; Traverso, Carlo Enrico; Izzotti, Alberto

    2016-08-01

    Glaucoma is a degenerative disease of the eye. Both the anterior and posterior segments of the eye are affected, extensive damage being detectable in the trabecular meshwork and the inner retina-central visual pathway complex. Oxidative stress is claimed to be mainly responsible for molecular damage in the anterior chamber. Indeed, oxidation harms the trabecular meshwork, leading eventually to endothelial cell decay, tissue malfunction, subclinical inflammation, changes in the extracellular matrix and cytoskeleton, altered motility, reduced outflow facility and (ultimately) increased IOP. Moreover, free radicals are involved in aging and can be produced in the brain (as well as in the eye) as a result of ischemia, leading to oxidation of the surrounding neurons. Glaucoma-related cell death occurs by means of apoptosis, and apoptosis is triggered by oxidative stress via (a) mitochondrial damage, (b) inflammation, (c) endothelial dysregulation and dysfunction, and (d) hypoxia. The proteomics of the aqueous humor is significantly altered in glaucoma as a result of oxidation-induced trabecular damage. Those proteins whose aqueous humor levels are increased in glaucoma are biomarkers of trabecular meshwork impairment. Their diffusion from the anterior to the posterior segment of the eye may be relevant in the cascade of events triggering apoptosis in the inner retinal layers, including the ganglion cells.

  8. Oxidative damage, skin aging, antioxidants and a novel antioxidant rating system.

    Science.gov (United States)

    Palmer, Debbie M; Kitchin, Jennifer Silverman

    2010-01-01

    It is believed that oxidative stress is caused by an imbalance between the production of reactive oxygen and a biological system's ability to neutralize the reactive intermediates. Oxidative damage occurs because of both intrinsic and extrinsic mechanisms. Together, intrinsic and extrinsic damage are the primary causes of skin aging. The skin uses a series of intrinsic antioxidants to protect itself from free radical damage. Naturally occurring extrinsic antioxidants have also been widely shown to offset and alleviate these changes. Unlike sunscreens, which have an SPF rating system to guide consumers in their purchases, there is no widely accepted method to choose antioxidant anti-aging products. ORAC (Oxygen Radical Absorbance Capacity) and ABEL-RAC (Analysis By Emitted Light-Relative Antioxidant Capacity), are both accepted worldwide as a standard measure of the antioxidant capacity of foods, and are rating systems that could be applied to all antioxidant skincare products. The standardization of antioxidant creams could revolutionize the cosmeceutical market and give physicians and consumers the ability to compare and choose effectively.

  9. Prioritization of reactor control components susceptible to fire damage as a consequence of aging

    Energy Technology Data Exchange (ETDEWEB)

    Lowry, W.; Vigil, R. [Science and Engineering Associates, Inc., Albuquerque, NM (United States); Nowlen, S. [Sandia National Labs., Albuquerque, NM (United States)

    1994-01-01

    The Fire Vulnerability of Aged Electrical Components Test Program is to identify and assess issues of plant aging that could lead to an increase in nuclear power plant risk because of fires. Historical component data and prior analyses are used to prioritize a list of components with respect to aging and fire vulnerability and the consequences of their failure on plant safety systems. The component list emphasizes safety system control components, but excludes cables, large equipment, and devices encompassed in the Equipment Qualification (EQ) program. The test program selected components identified in a utility survey and developed test and fire conditions necessary to maximize the effectiveness of the test program. Fire damage considerations were limited to purely thermal effects.

  10. 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.

  11. 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

  12. Metabolic Damage and Premature Thymus Aging Caused by Stromal Catalase Deficiency.

    Science.gov (United States)

    Griffith, Ann V; Venables, Thomas; Shi, Jianjun; Farr, Andrew; van Remmen, Holly; Szweda, Luke; Fallahi, Mohammad; Rabinovitch, Peter; Petrie, Howard T

    2015-08-18

    T lymphocytes are essential mediators of immunity that are produced by the thymus in proportion to its size. The thymus atrophies rapidly with age, resulting in progressive diminution of new T cell production. This decreased output is compensated by duplication of existing T cells, but it results in gradual dominance by memory T cells and decreased ability to respond to new pathogens or vaccines. Here, we show that accelerated and irreversible thymic atrophy results from stromal deficiency in the reducing enzyme catalase, leading to increased damage by hydrogen peroxide generated by aerobic metabolism. Genetic complementation of catalase in stromal cells diminished atrophy, as did chemical antioxidants, thus providing a mechanistic link between antioxidants, metabolism, and normal immune function. We propose that irreversible thymic atrophy represents a conventional aging process that is accelerated by stromal catalase deficiency in the context of an intensely anabolic (lymphoid) environment.

  13. Metabolic Damage and Premature Thymus Aging Caused by Stromal Catalase Deficiency

    Directory of Open Access Journals (Sweden)

    Ann V. Griffith

    2015-08-01

    Full Text Available T lymphocytes are essential mediators of immunity that are produced by the thymus in proportion to its size. The thymus atrophies rapidly with age, resulting in progressive diminution of new T cell production. This decreased output is compensated by duplication of existing T cells, but it results in gradual dominance by memory T cells and decreased ability to respond to new pathogens or vaccines. Here, we show that accelerated and irreversible thymic atrophy results from stromal deficiency in the reducing enzyme catalase, leading to increased damage by hydrogen peroxide generated by aerobic metabolism. Genetic complementation of catalase in stromal cells diminished atrophy, as did chemical antioxidants, thus providing a mechanistic link between antioxidants, metabolism, and normal immune function. We propose that irreversible thymic atrophy represents a conventional aging process that is accelerated by stromal catalase deficiency in the context of an intensely anabolic (lymphoid environment.

  14. Photo-damage, photo-protection and age-related macular degeneration.

    Science.gov (United States)

    Marquioni-Ramella, Melisa D; Suburo, Angela M

    2015-09-26

    Age-related macular degeneration (AMD) is a degenerative retinal disease that causes blindness in people 60-65 years and older, with the highest prevalence appearing in people 90 years-old or more. Epidemiological estimates indicate that the number of cases is increasing, and will almost double in the next 20 years. Preventive measures require precise etiological knowledge. This is quite difficult, since AMD is a multifactorial condition with intricate relationships between causes and risk factors. In this review, we describe the impact of light on the structure and physiology of the retina and the pigment epithelium, taking into account the continuous exposure to natural and artificial light sources along the life of an individual. A large body of experimental evidence demonstrates the toxic effects of some lighting conditions on the retina and the pigment epithelium, and consensus exists about the importance of photo-oxidation phenomena in the causality chain between light and retinal damage. Here, we analyzed the transmission of light to the retina, and compared the aging human macula in healthy and diseased retinas, as shown by histology and non-invasive imaging systems. Finally, we have compared the putative retinal photo-sensitive molecular structures that might be involved in the genesis of AMD. The relationship between these compounds and retinal damage supports the hypothesis of light as an important initiating cause of AMD.

  15. 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

  16. 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.

  17. The free-radical damage theory: Accumulating evidence against a simple link of oxidative stress to ageing and lifespan.

    Science.gov (United States)

    Speakman, John R; Selman, Colin

    2011-04-01

    Recent work on a small European cave salamander (Proteus anguinus) has revealed that it has exceptional longevity, yet it appears to have unexceptional defences against oxidative damage. This paper comes at the end of a string of other studies that are calling into question the free-radical damage theory of ageing. This theory rose to prominence in the 1990s as the dominant theory for why we age and die. Despite substantial correlative evidence to support it, studies in the last five years have raised doubts over its importance. In particular, these include studies of mice with the major antioxidant genes knocked out (both singly and in combination), which show the expected elevation in oxidative damage but no impact on lifespan. Combined, these findings raise fundamental questions over whether the free-radical damage theory remains useful for understanding the ageing process, and variation in lifespan and life histories.

  18. Oxidative damage parameters in renal tissues of aged and young rats based on gender

    Directory of Open Access Journals (Sweden)

    Uzun D

    2013-06-01

    young control group for both genders. Conclusion: With respect to PCO and AOPP, impaired redox homeostasis is substantially more prominent in males than females. The decrease of G-SH levels in male groups could be attributed to stabilizing the redox status of protein thiol groups by the depletion of the GSH groups. Considering the results, the renal tissue proteins and lipids in different genders may have different susceptibilities to oxidative damage. Keywords: lipid peroxidation, protein oxidation, radicals, renal aging

  19. 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

    BACKGROUND: Many patients and healthcare professionals believe that work-related psychosocial stress, such as job strain, can make asthma worse, but this is not corroborated by empirical evidence. We investigated the associations between job strain and the incidence of severe asthma exacerbations...... asthma exacerbations were ascertained from national hospitalization and death registries. Associations between job strain and asthma exacerbations were modelled using Cox regression and the study-specific findings combined using random-effects meta-analyses. RESULTS: During a median follow-up of 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: 1.27, 95...

  20. 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

  1. Exacerbations of asthma during pregnancy

    DEFF Research Database (Denmark)

    Ali, Z; 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...... 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....

  2. Simulation of thermal ageing and radiation damage in Fe-Cr

    Energy Technology Data Exchange (ETDEWEB)

    Wallenius, Janne [Department of Reactor Physics, KTH, AlbaNova University Centre, 106 91 Stockholm (Sweden)]. E-mail: janne@neutron.kth.se; Olsson, Paer [Department Materiaux et Mecanique des Composants, Electricite de France, EDF-R and D, Les Renardieres, F-77250 Moret sur Loing (France); Malerba, Lorenzo [SCK-CEN, Belgian Nuclear Research Centre, Boeretang 200, B-2400 Mol (Belgium); Terentyev, Dmitry [SCK-CEN, Belgian Nuclear Research Centre, Boeretang 200, B-2400 Mol (Belgium)

    2007-02-15

    In recent years substantial progress has been made in the field of multi-scale modelling of radiation damage Fe-Cr alloy. Ab initio calculations have provided a description of point-defect properties for a large number of defect configurations. Empirical potentials for the alloy of EAM and 2nd moment tight binding type have been constructed that reproduce these formation energies, as well as the anomalous shift in sign of mixing enthalpy at a Cr concentration of about 10%. Applying the potentials in simulation of interstitial cluster transport, it has been found that cluster diffusion coefficients have shallow minima corresponding to experimentally measured minima in swelling rates of Fe-Cr alloys. Kinetic Monte Carlo simulation of thermal ageing further show that these potentials correctly reproduce the formation modes of the alpha-prime phase for Cr concentrations above 9%. The present paper is a review of methods used and results achieved within the last couple of years.

  3. 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).

  4. 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...

  5. Prevalence, and Intellectual Outcome of Unilateral Focal Cortical Brain Damage as a Function of Age, Sex and Aetiology

    Directory of Open Access Journals (Sweden)

    C. M. J. Braun

    2002-01-01

    Full Text Available Neurologists and neuropsychologists are aware that aging men are more at risk than women for brain damage, principally because of the well known male-predominant risk for cardiovascular disease and related cerebrovascular accidents. However, a disproportion in prevalence of brain damage between the sexes in childhood may be less suspected. Furthermore, sex-specific risk for other aetiologies of brain damage may be little known, whether in the pediatric or adult populations. Proposals of a sex difference in cognitive recovery from brain damage have also been controversial. Six hundred and thirty five “consecutive” cases with cortical focal lesions including cases of all ages and both sexes were reviewed. Aetiology of the lesion was determined for each case as was postlesion IQ. Risk was highly male prevalent in all age groups, with a predominance of cardiovascular aetiology explaining much of the adult male prevalence. However, several other aetiological categories were significantly male prevalent in juveniles (mitotic, traumatic, dysplasic and adults (mitotic, traumatic. There was no sex difference in outcome (i.e., postlesion IQ of these cortical brain lesions for the cohort as a whole, after statistical removal of the influence of lesion extent, aetiology and presence of epilepsy. Mechanisms potentially responsible for sex differences in prevalence, aetiology of brain damage, and recovery, are reviewed and discussed.

  6. The effect of aging on the DNA damage and repair capacity in 2BS cells undergoing oxidative stress.

    Science.gov (United States)

    Wang, Jin-Ling; Wang, Pei-Chang

    2012-01-01

    Aging is associated with a reduction in the DNA repair capacity under oxidative stress. However, whether the DNA damage and repair capacity can be a biomarker of aging remains controversial. In this study, we demonstrated two cause-and-effect relationships, the one is between the DNA damage and repair capacity and the cellular age, another is between DNA damage and repair capacity and the level of oxidative stress in human embryonic lung fibroblasts (2BS) exposed to different doses of hydrogen peroxide (H2O2). To clarify the mechanisms of the age-related reduction in DNA damage and repair capacity, we preliminarily evaluated the expressions of six kinds of pivotal enzymes involved in the two classical DNA repair pathways. The DNA repair capacity was observed in human fibroblasts cells using the comet assay; the age-related DNA repair enzymes were selected by RT-PCR and then verified by Western blot in vitro. Results showed that the DNA repair capacity was negatively and linearly correlated with (i) cumulative population doubling (PD) levels only in the group of low concentration of hydrogen peroxide treatment, (ii) with the level of oxidative stress only in the group of young PD cells. The mRNA expression of DNA polymerase δ1 decreased substantially in senescent cells and showed negative linear-correlation with PD levels; the protein expression level was well consistent with the mRNA level. Taken together, DNA damage and repair capacity can be a biomarker of aging. Reduced expression of DNA polymerase δ1 may be responsible for the decrease of DNA repair capacity in senescent cells.

  7. 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

  8. 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

  9. Predictors of Hospitalized Exacerbations and Mortality in Chronic Obstructive Pulmonary Disease.

    Directory of Open Access Journals (Sweden)

    Miguel Santibáñez

    Full Text Available Exacerbations of chronic obstructive pulmonary disease (COPD carry significant consequences for patients and are responsible for considerable health-care costs-particularly if hospitalization is required. Despite the importance of hospitalized exacerbations, relatively little is known about their determinants. This study aimed to analyze predictors of hospitalized exacerbations and mortality in COPD patients.This was a retrospective population-based cohort study. We selected 900 patients with confirmed COPD aged ≥35 years by simple random sampling among all COPD patients in Cantabria (northern Spain on December 31, 2011. We defined moderate exacerbations as events that led a care provider to prescribe antibiotics or corticosteroids and severe exacerbations as exacerbations requiring hospital admission. We observed exacerbation frequency over the previous year (2011 and following year (2012. We categorized patients according to COPD severity based on forced expiratory volume in 1 second (Global Initiative for Chronic Obstructive Lung Disease [GOLD] grades 1-4. We estimated the odds ratios (ORs by logistic regression, adjusting for age, sex, smoking status, COPD severity, and frequent exacerbator phenotype the previous year.Of the patients, 16.4% had ≥1 severe exacerbations, varying from 9.3% in mild GOLD grade 1 to 44% in very severe COPD patients. A history of at least two prior severe exacerbations was positively associated with new severe exacerbations (adjusted OR, 6.73; 95% confidence interval [CI], 3.53-12.83 and mortality (adjusted OR, 7.63; 95%CI, 3.41-17.05. Older age and several comorbidities, such as heart failure and diabetes, were similarly associated.Hospitalized exacerbations occurred with all grades of airflow limitation. A history of severe exacerbations was associated with new hospitalized exacerbations and mortality.

  10. 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

  11. Effect of ageing in fibre bundle models on the evolution of acoustic and silent damage in time-dependent failure

    Science.gov (United States)

    Lennartz, S.; Main, I. G.; Zaiser, M.; Kun, F.

    2012-04-01

    The spatio-temporal evolution of damage in brittle materials is often modelled by fibre bundle models. In real fibre bundles (such as suspension bridge ropes), and in other composite materials such as rocks and ceramics, the evolution of damage as a function of stress and time can be recorded using acoustic emissions (AE), and used to asses the integrity of the sample and its lifetime. Such monitoring however tells only part of the story, since time-dependent, effectively 'silent' damage also occurs without AE, and small AE events may not be recorded below some recording threshold set by the background noise. The proportion of seismic to aseismic deformation is important for a number of applications, for example providing a strong constraint on plate boundary dynamics and estimates of earthquake hazard. Accordingly we have modified the usual fibre bundle model by introducing some additional ageing, which results in silent damage below a nominal threshold for more dynamic deformation. This enables us to model the effect of the model parameters on the ratio of acoustic to total damage, and how it evolves in time under a given stress history. We found that the silent damage dominates the process and that for a constant applied stress the ratio between acoustic and silent emissions is approximately constant over a wide range of time. The proportionality factor depends strongly on the applied stress and only weakly on the ageing parameter, while it is the other way around for the failure time which depends more on the ageing parameter than on the applied stress.

  12. Postoperative Cognitive Deficits Triggered by Surgical Trauma Are Exacerbated in Aged Rats%手术创伤对老年鼠和成年鼠术后空间学习记忆能力的影响

    Institute of Scientific and Technical Information of China (English)

    曹学照; 郭丽丽; 马虹

    2012-01-01

    Objective To investigate the effects of partial hepatectomy on spatial learning and memory in adult and aged rats. Methods Both adult (3~6 months old) and aged (20-24 months old) Sprague-Dawley male rats were randomly divided into following groups:control (n =12 for each group),anesthesia alone (n =36 for each group),and operation group (n =36 for each group). Control animals didn't received special treatment except sterile saline. The anesthesia alone group received 1.5% to 2% isoflurane with intubation and mechanical ventilation. The operation group underwent partial hepatectomy under general anesthesia. Cognitive function was assessed in a reversal-learning version of the Morris water maze (MWM) before and after surgery. Results Surgical trauma resulted in impairments in distance and latency only on postoperative day 1 (P < 0.001,respectively) in adult rats. Aged rats exhibited impairments on day 1 (P < 0.001) that persisted until postoperative day 3 (P =0.002 and P =0.001 .respectively). Conclusion These findings suggest that surgical trauma,rather than anesthesia, resulted in cognitive function impairment which would be exacerbated by aging.%目的 探讨手术创伤对老年鼠和成年鼠肝部分切除术后空间学习记忆能力的影响.方法 成年和老年SD大鼠随机分为对照组、麻醉组、手术组,对照组SD大鼠不做特殊处理.麻醉组实验动物单纯接受1.5%~2%异氟醚麻醉,行气管插管和机械通气.手术组SD大鼠行肝部分切除术.Morris水迷宫用于检测实验鼠的空间学习记忆能力.结果 成年鼠的空间记忆学习能力到达平台时间和游行距离在术后1 d(P<0.001)受到破坏,在术后3d恢复(P=0.848,P=0.973).老年鼠的空间记忆学习能力在术后1 d(P< 0.001)受到破坏,并且持续到术后3 d(P =0.002,P=0.001),在术后7d恢复.结论 手术创伤而不是麻醉因素导致了术后认知功能障碍,高龄加剧了认知功能的破坏.

  13. COPD exacerbations, inflammation and treatment

    NARCIS (Netherlands)

    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 t

  14. Elevation of cartilage AGEs does not accelerate initiation of canine experimental osteoarthritis upon mild surgical damage

    NARCIS (Netherlands)

    Vos, P.A.J.M.; Degroot, J.; Barten-Van Rijbroek, A.D.; Zuurmond, A.-M.; Bijlsma, J.W.J.; Mastbergen, S.C.; Lafeber, F.P.J.G.

    2012-01-01

    Osteoarthritis is a highly prevalent disease, age being the main risk factor. The age-related accumulation of advanced-glycation-endproducts (AGEs) adversely affects the mechanical and biochemical properties of cartilage. The hypothesis that accumulation of cartilage AGEs in combination with surgica

  15. 25-Hydroxyvitamin D3-deficiency enhances oxidative stress and corticosteroid resistance in severe asthma exacerbation.

    Directory of Open Access Journals (Sweden)

    Nan Lan

    Full Text Available Oxidative stress plays a significant role in exacerbation of asthma. The role of vitamin D in oxidative stress and asthma exacerbation remains unclear. We aimed to determine the relationship between vitamin D status and oxidative stress in asthma exacerbation. Severe asthma exacerbation patients with 25-hydroxyvitamin D3-deficiency (V-D deficiency or 25-hydroxyvitamin D-sufficiency (V-D sufficiency were enrolled. Severe asthma exacerbation with V-D-deficiency showed lower forced expiratory volume in one second (FEV1 compared to that with V-D-sufficiency. V-D-deficiency intensified ROS release and DNA damage and increased TNF-α, OGG1 and NFκB expression and NFκB phosphorylation in severe asthma exacerbation. Supplemental vitamin D3 significantly increased the rates of FEV1 change and decreased ROS and DNA damage in V-D-deficiency. Vitamin D3 inhibited LPS-induced ROS and DNA damage and were associated with a decline in TNF-α and NFκB in epithelial cells. H2O2 reduces nuclear translocation of glucocorticoid receptors in airway epithelial cell lines. V-D pretreatment enhanced the dexamethasone-induced nuclear translocation of glucocorticoid receptors in airway epithelial cell lines and monocytes from 25-hydroxyvitamin D3-deficiency asthma patients. These findings indicate that V-D deficiency aggravates oxidative stress and DNA damage, suggesting a possible mechanism for corticosteroid resistance in severe asthma exacerbation.

  16. 25-Hydroxyvitamin D3-deficiency enhances oxidative stress and corticosteroid resistance in severe asthma exacerbation.

    Science.gov (United States)

    Lan, Nan; Luo, Guangyan; Yang, Xiaoqiong; Cheng, Yuanyuan; Zhang, Yun; Wang, Xiaoyun; Wang, Xing; Xie, Tao; Li, Guoping; Liu, Zhigang; Zhong, Nanshan

    2014-01-01

    Oxidative stress plays a significant role in exacerbation of asthma. The role of vitamin D in oxidative stress and asthma exacerbation remains unclear. We aimed to determine the relationship between vitamin D status and oxidative stress in asthma exacerbation. Severe asthma exacerbation patients with 25-hydroxyvitamin D3-deficiency (V-D deficiency) or 25-hydroxyvitamin D-sufficiency (V-D sufficiency) were enrolled. Severe asthma exacerbation with V-D-deficiency showed lower forced expiratory volume in one second (FEV1) compared to that with V-D-sufficiency. V-D-deficiency intensified ROS release and DNA damage and increased TNF-α, OGG1 and NFκB expression and NFκB phosphorylation in severe asthma exacerbation. Supplemental vitamin D3 significantly increased the rates of FEV1 change and decreased ROS and DNA damage in V-D-deficiency. Vitamin D3 inhibited LPS-induced ROS and DNA damage and were associated with a decline in TNF-α and NFκB in epithelial cells. H2O2 reduces nuclear translocation of glucocorticoid receptors in airway epithelial cell lines. V-D pretreatment enhanced the dexamethasone-induced nuclear translocation of glucocorticoid receptors in airway epithelial cell lines and monocytes from 25-hydroxyvitamin D3-deficiency asthma patients. These findings indicate that V-D deficiency aggravates oxidative stress and DNA damage, suggesting a possible mechanism for corticosteroid resistance in severe asthma exacerbation.

  17. 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.

  18. 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.)

  19. 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 – ...

  20. 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,

  1. 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.

  2. Innovation aspects of rehabilitation methods of treatment of acetabulum dam-age

    Directory of Open Access Journals (Sweden)

    Muhammad Shorustamov

    2012-05-01

    Full Text Available The article is devoted to solving improvement of rehabilitation treatment methods in acetabular injuries. Offered algorithm enables to improve rehabilitation treatment methods of acetabular injuries. Algorithm of rehabilitation includes blocks of conservative (including blocks ambulatory, treatment at a health resort, medicamentous and other methods of treatment of acetabulum damage as well as control block. Block of endoprosthetics of coxofemoral joint is also provided for in case of detection of signs of coxarthrosis. Innovation algorithm of perfecting rehabilitation methods of treatment of acetabulum damage (AD contributes to expansion of an implementation sphere in traumatic surgery and orthopedics practice. It allows practical physicians to build a clear algorithm of postoperative rehabilitation for this complicated cohort of patients with AD.

  3. Oxidative damage impact on aging and age-related diseases: drug targeting of telomere attrition and dynamic telomerase activity flirting with imidazole-containing dipeptides.

    Science.gov (United States)

    Babizhayev, Mark A; Vishnyakova, Khava S; Yegorov, Yegor E

    2014-01-01

    It has been documented that telomere-associated cellular senescence may contribute to certain age-related disorders, including an increase in cancer incidence, wrinkling and diminished skin elasticity, atherosclerosis, osteoporosis, weight loss, age-related cataract, glaucoma and others. Shorter telomere length in leukocytes was associated crosssectionally with cardiovascular disorders and their risk factors, including pulse pressure and vascular aging, obesity, vascular dementia, diabetes, coronary artery disease, myocardial infarction (although not in all studies), cellular turnover and exposure to oxidative and inflammatory damage in chronic obstructive pulmonary disease. It has been proposed that telomere length may not be a strong biomarker of survival in older individuals, but it may be an informative biomarker of healthy aging. The data reveal that telomere dynamics and changes in telomerase activity are consistent elements of cellular alterations associated with changes in proliferative state and in this article these processes are consequently considered as the new therapeutic drug targets for physiological control with advanced drug delivery and nutritional formulations. In particular, the presence of highly specific correlations and early causal relationships between telomere loss in the absence of telomerase activity and replicative senescence or crisis, and from the other side, telomerase reactivation and cell immortality, point to new and important treatment strategies or the therapeutic manipulation during treatment of age related disorders and cancer. Once better controls and therapeutic treatments for aging and age-related disorders are achieved, cellular rejuvenation by manipulating telomeres and enzyme telomerase activity may reduce some of the physiological declines that accompany aging. In this work, we raise and support a therapeutic concept of using non-hydrolyzed forms of naturally occurring imidazoledipeptide based compounds carnosine and

  4. Aging aggravates ischemic stroke-induced brain damage in mice with chronic peripheral infection.

    Science.gov (United States)

    Dhungana, Hiramani; Malm, Tarja; Denes, Adam; Valonen, Piia; Wojciechowski, Sara; Magga, Johanna; Savchenko, Ekaterina; Humphreys, Neil; Grencis, Richard; Rothwell, Nancy; Koistinaho, Jari

    2013-10-01

    Ischemic stroke is confounded by conditions such as atherosclerosis, diabetes, and infection, all of which alter peripheral inflammatory processes with concomitant impact on stroke outcome. The majority of the stroke patients are elderly, but the impact of interactions between aging and inflammation on stroke remains unknown. We thus investigated the influence of age on the outcome of stroke in animals predisposed to systemic chronic infection. Th1-polarized chronic systemic infection was induced in 18-22 month and 4-month-old C57BL/6j mice by administration of Trichuris muris (gut parasite). One month after infection, mice underwent permanent middle cerebral artery occlusion and infarct size, brain gliosis, and brain and plasma cytokine profiles were analyzed. Chronic infection increased the infarct size in aged but not in young mice at 24 h. Aged, ischemic mice showed altered plasma and brain cytokine responses, while the lesion size correlated with plasma prestroke levels of RANTES. Moreover, the old, infected mice exhibited significantly increased neutrophil recruitment and upregulation of both plasma interleukin-17α and tumor necrosis factor-α levels. Neither age nor infection status alone or in combination altered the ischemia-induced brain microgliosis. Our results show that chronic peripheral infection in aged animals renders the brain more vulnerable to ischemic insults, possibly by increasing the invasion of neutrophils and altering the inflammation status in the blood and brain. Understanding the interactions between age and infections is crucial for developing a better therapeutic regimen for ischemic stroke and when modeling it as a disease of the elderly.

  5. 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...

  6. 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

  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

    , 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...

  8. Calcium antagonists decrease capillary wall damage in aging hypertensive rat brain

    NARCIS (Netherlands)

    Farkas, E.; de Jong, G.I.; Apro, E.; Keuker, J.I.H.; Luiten, P.G.M.

    2001-01-01

    Chronic hypertension during aging is a serious threat to the cerebral vasculature. The larger brain arteries can react to hypertension with an abnormal wall thickening, a loss of elasticity and a narrowed lumen. However, little is known about the hypertension-induced alterations of cerebral capillar

  9. 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.

  10. 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

  11. 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

  12. 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).

  13. 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

  14. 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

  15. 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.

  16. 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)

  17. 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

  18. 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.

  19. 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)

  20. 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.

  1. 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.

  2. 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...

  3. An international observational prospective study to determine the cost of asthma exacerbations (COAX).

    Science.gov (United States)

    Lane, Stephen; Molina, Jesus; Plusa, Tadeusz

    2006-03-01

    Asthma is a common chronic condition that places substantial burden on patients and healthcare services. Despite the standards of asthma control that international guidelines recommend should be achieved, many patients continue to suffer sub-optimal control of symptoms and experience exacerbations (acute asthma attacks). In addition to being associated with reduced quality of life, asthma exacerbations are a key cost driver in asthma management. Routine clinical practice for the management of asthma exacerbations varies in different healthcare systems, so healthcare providers require local costs to be able to assess the value of therapies that reduce the frequency and severity of exacerbations. This prospective study, conducted in a total of 15 countries, assessed the local cost of asthma exacerbations managed in either primary or secondary care. Healthcare resources used were costed using actual values appropriate to each country in local currency and in Euros. Results are presented for exacerbations managed in primary care in Brazil, Bulgaria, Croatia, Czech Republic, Hungary, Poland, Russia, Slovakia, Slovenia, Spain and Ukraine, and in secondary care in Croatia, Denmark, Ireland, Latvia, Norway, Poland, Russia, Slovakia, Slovenia and Spain. Multiple regression analysis of the 2052 exacerbations included in the economic analysis showed that the cost of exacerbations was significantly affected by country (P<0.0001). Mean costs were significantly higher in secondary care (euro 1349) than primary care (euro 445, P=0.0003). Age was a significant variable (P=0.0002), though the effect showed an interaction with care type (P<0.0001). As severity of exacerbation increased, so did secondary care costs, though primary care costs remained essentially constant. In conclusion, the study showed that asthma exacerbations are costly to manage, suggesting that therapies able to increase asthma control and reduce the frequency or severity of exacerbations may bring economic

  4. Clinical characteristics of eosinophilic asthma exacerbations

    DEFF Research Database (Denmark)

    Bjerregaard, Asger; Laing, Ingrid A; Backer, Vibeke;

    2016-01-01

    BACKGROUND AND OBJECTIVE: Airway eosinophilia is associated with an increased risk of asthma exacerbations; however, the impact on the severity of exacerbations is largely unknown. We describe the sputum inflammatory phenotype during asthma exacerbation and correlate it with severity and treatment...... response. METHODS: Patients presenting to hospital with an asthma exacerbation were recruited during a 12-month period and followed up after 4 weeks. Induced sputum was collected at both visits. Patients underwent spirometry, arterial blood gas analysis, fractional exhaled nitric oxide analysis, white...... with a sensitivity of 86% and a specificity of 70%. CONCLUSION: Our findings suggest that eosinophilic asthma exacerbations may be clinically more severe than NEEs, supporting the identification of these higher risk patients for specific interventions....

  5. 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

  6. COPD exacerbation frequency and its association with health care resource utilization and costs

    Directory of Open Access Journals (Sweden)

    Dhamane AD

    2015-12-01

    Full Text Available Amol D Dhamane,1 Chad Moretz,2 Yunping Zhou,2 Kate Burslem,1 Kim Saverno,2 Gagan Jain,1 Andrew Renda,3 Shuchita Kaila1 1Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA; 2Comprehensive Health Insights Inc., Louisville, KY, USA; 3Humana Inc., Louisville, KY, USA Background: Chronic obstructive pulmonary disease (COPD exacerbations account for a substantial proportion of COPD-related costs.Objective: To describe COPD exacerbation patterns and assess the association between exacerbation frequency and health care resource utilization (HCRU and costs in patients with COPD in a Medicare population.Methods: A retrospective cohort study utilizing data from a large US national health plan was conducted including patients with a COPD diagnosis during January 1, 2007 to December 31, 2012, aged 40–89 years and continuously enrolled in a Medicare Advantage Prescription Drug plan. Exacerbation frequency, HCRU, and costs were assessed during a 24-month period following the first COPD diagnosis (follow-up period. Four cohorts were created based on exacerbation frequency (zero, one, two, and ≥three. HCRU and costs were compared among the four cohorts using chi-square tests and analysis of variance, respectively. A trend analysis was performed to assess the association between exacerbation frequency and costs using generalized linear models.Results: Of the included 52,459 patients, 44.3% had at least one exacerbation; 26.3%, 9.5%, and 8.5% had one, two, and ≥three exacerbations in the 24-month follow-up period, respectively. HCRU was significantly different among cohorts (all P<0.001. In patients with zero, one, two, and ≥three exacerbations, the percentages of patients experiencing all-cause hospitalizations were 49.7%, 66.4%, 69.7%, and 77.8%, respectively, and those experiencing COPD-related hospitalizations were 0%, 40.4%, 48.1%, and 60.5%, respectively. Mean all-cause total costs (medical and pharmacy were more than twofold greater in

  7. 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 ...

  8. Aging and amyloid beta-induced oxidative DNA damage and mitochondrial dysfunction in Alzheimer's disease: implications for early intervention and therapeutics.

    Science.gov (United States)

    Mao, Peizhong; Reddy, P Hemachandra

    2011-11-01

    Alzheimer's disease (AD) is an age-related progressive neurodegenerative disease affecting thousands of people in the world and effective treatment is still not available. Over two decades of intense research using AD postmortem brains, transgenic mouse and cell models of amyloid precursor protein and tau revealed that amyloid beta (Aβ) and hyperphosphorylated tau are synergistically involved in triggering disease progression. Accumulating evidence also revealed that aging and amyloid beta-induced oxidative DNA damage and mitochondrial dysfunction initiate and contributes to the development and progression of the disease. The purpose of this article is to summarize the latest progress in aging and AD, with a special emphasis on the mitochondria, oxidative DNA damage including methods of its measurement. It also discusses the therapeutic approaches against oxidative DNA damage and treatment strategies in AD.

  9. 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.

  10. 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...

  11. 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...

  12. 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 ...

  13. 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...

  14. The Contact Ageing Effect on Fretting Damage of an Electro-Deposited Coating against an AISI52100 Steel Ball

    Directory of Open Access Journals (Sweden)

    Kyungmok Kim

    2016-09-01

    Full Text Available This article investigates the effect of contact ageing on fretting damage of an epoxy-based cathodic electro-deposited coating for use on automotive seat slide tracks (made of cold-rolled high strength steel. Static normal load was induced at the contact between the coating and an AISI52100 ball for a certain duration. It was identified that plastically deformed contact area increased logarithmically as a function of time when the contact was under static normal load. Fretting tests after various durations of static contact were conducted using a ball-on-flat plate apparatus. All fretting tests were halted when the friction coefficient reached a critical value of 0.5, indicating complete coating failure. The total number of fretting cycles to the critical friction coefficient was found to vary with the duration of static contact before fretting. It was identified that the number of cycles to the critical friction coefficient decreased with the increased duration of static contact. Meanwhile, the friction coefficient at steady-state sliding was not greatly affected by the duration of static contact before fretting. Finally, the relation between coating thickness after indentation creep and the number of cycles to the critical friction coefficient was found to be linear. Obtained results show that the duration of static contact before fretting has an influence on the fretting lifetime of an electro-deposited coating.

  15. 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

  16. 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.

  17. Pulmonary Exacerbations in Children with Cystic Fibrosis.

    Science.gov (United States)

    Waters, Valerie; Ratjen, Felix

    2015-11-01

    Pulmonary exacerbations treated with intravenous antibiotics have significant, well-characterized negative consequences on clinical outcomes in cystic fibrosis (CF). The impact of milder exacerbations in children with CF, commonly treated with oral antibiotics, are less well defined. Pulmonary exacerbations have multiple triggers, but viral infections are particularly common in children. Children with CF and healthy control subjects have similar frequencies of viral respiratory infections, but there is evidence of greater virus-related morbidity in patients with CF, likely due to a combination of increased viral load, more pronounced inflammatory response, and more pronounced impairment in mucociliary clearance. In recent clinical trials in children, definitions have been used that are more symptom based rather than intervention based. These studies have demonstrated differences in the spectrum of symptoms between children and older patients but have also shown that, despite low threshold definitions, a considerable number of patients receive treatment for events not fulfilling the pulmonary exacerbation criteria. Additional research is needed to determine the impact of these milder exacerbations on lung function recovery and time to subsequent exacerbation as well as long-term outcomes such as mortality. PMID:26595740

  18. 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

  19. 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...

  20. 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.

  1. 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.

  2. 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

  3. 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

  4. 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

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

    Science.gov (United States)

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

    2011-03-01

    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 elevated once the process of exacerbation has been initiated. Identifying biomarkers that can predict the onset of pulmonary exacerbation at an early stage would provide an opportunity to intervene before the establishment of a substantial immune response, with major implications for the advancement of cystic fibrosis care. The precise triggers of pulmonary exacerbation remain to be determined; however, the majority of models relate to the activity of microbes present in the patient's lower airways of cystic fibrosis. Advances in diagnostic microbiology now allow for the examination of these complex systems at a level likely to identify factors on which biomarker assays can be based. In this article, we discuss key considerations in the design and testing of assays that could predict pulmonary exacerbations. PMID:21405970

  6. Patterns, predictors and outcomes of asthma control and exacerbations during pregnancy: a prospective cohort study

    Directory of Open Access Journals (Sweden)

    Luke E. Grzeskowiak

    2016-02-01

    Full Text Available There exists a paucity of data for socially disadvantaged populations describing patterns and predictors of asthma control status and exacerbations during pregnancy, and their relationship to adverse perinatal outcomes. Asthmatic women (n=189 were followed prospectively during pregnancy, with visits at 12, 20, 28 and 36 weeks gestation. Data on loss of control, recurrent uncontrolled asthma and moderate/severe exacerbations were collected at each visit and their relationship to perinatal outcomes examined following stratification for fetal sex. 50% of asthmatic women experienced a loss of control or moderate/severe exacerbation during pregnancy, with 22% of women experiencing a moderate/severe exacerbation. Factors associated with an increased risk of women experiencing recurrent uncontrolled asthma during pregnancy included smoking (relative risk 2.92, 95% CI 1.53–5.58, inhaled corticosteroid use at the beginning of pregnancy (relative risk 2.40, 95% CI 1.25–4.60 and increasing maternal age (relative risk 1.06, 95% CI 1.01–1.11. No factors were associated with moderate/severe exacerbations. Asthma control rather than exacerbations during pregnancy appeared to be most strongly correlated with perinatal outcomes. Following stratification by fetal sex, the presence of recurrent uncontrolled asthma was associated with an increased risk of being small for gestational age in women pregnant with females (33.3% versus 9.5%; p=0.018. In contrast, there was a nonsignificant increased risk of preterm birth in women with recurrent uncontrolled asthma that were pregnant with males (25.0% versus 11.8%; p=0.201 These results suggest that the key to improving perinatal outcomes lies in improving asthma control as early as possible in pregnancy and monitoring throughout pregnancy, rather than focusing on preventing exacerbations alone.

  7. 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.

  8. Radiation-Induced Esophagitis Exacerbated by Everolimus

    Directory of Open Access Journals (Sweden)

    Yuji Miura

    2013-06-01

    Full Text Available Background: Everolimus, a potent mammalian target of rapamycin (mTOR inhibitor, has shown anticancer activity against various types of cancer, including renal cell carcinoma (RCC; however, little information is available on the efficacy and safety of the combination of everolimus and radiotherapy. We report a case of radiation-induced esophagitis that might have been exacerbated by the sequential administration of everolimus. Case Presentation: A 63-year-old Japanese man with RCC complained of back pain, and magnetic resonance imaging revealed vertebral metastases. He received radiotherapy (30 Gy/10 fractions to the T6-10 vertebrae. Everolimus was administered immediately after the completion of radiotherapy. One week later, he complained of dysphagia, nausea and vomiting. An endoscopic examination of the esophagus showed erosive esophagitis in the middle to lower portions of his thoracic esophagus, corresponding to the irradiation field. Conclusion: Clinicians should be aware that everolimus might lead to the unexpected exacerbation of radiation toxicities.

  9. 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.

  10. 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...

  11. 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.

  12. Chest pain and exacerbations of bronchiectasis

    Directory of Open Access Journals (Sweden)

    King PT

    2012-12-01

    Full Text Available Paul T King,1,2 Stephen R Holdsworth,2 Michael Farmer,1 Nicholas J Freezer,1 Peter W Holmes11Department of Respiratory and Sleep Medicine, 2Monash University Department of Medicine, Monash Medical Centre, Melbourne, Victoria, AustraliaBackground: Bronchiectasis is a common disease and a major cause of respiratory morbidity. Chest pain has been described as occurring in the context of bronchiectasis but has not been well characterized. This study was performed to describe the characteristics of chest pain in adult bronchiectasis and to define the relationship of this pain to exacerbations.Subjects and methods: We performed a prospective study of 178 patients who were followed-up for 8 years. Subjects were reviewed on a yearly basis and assessed for the presence of chest pain. Subjects who had chest pain at the time of clinical review by the investigators were included in this study. Forty-four patients (25% described respiratory chest pain at the time of assessment; in the majority of cases 39/44 (89%, this occurred with an exacerbation and two distinct types of chest pain could be described: pleuritic (n = 4 and non-pleuritic (n = 37, with two subjects describing both forms. The non-pleuritic chest pain occurred most commonly over both lower lobes and was mild to moderate in severity. The pain subsided as patients recovered. Conclusion: Non-pleuritic chest pain occurs in subjects with bronchiectasis generally in association with exacerbations.Keywords: sputum, collapse, bronchitis, airway obstruction

  13. 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.

  14. 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

  15. 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, parall...

  16. 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...

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

    Science.gov (United States)

    Lee, Hyun; Rhee, Chin Kook; Lee, Byung-Jae; Choi, Dong-Chull; Kim, Jee-Ae; Kim, Sang Hyun; Jeong, Yoolwon; Kim, Tae-Hyung; Chon, Gyu Rak; Jung, Ki-Suck; Lee, Sang Haak; Price, David; Yoo, Kwang Ha; Park, Hye Yun

    2016-01-01

    Background Acute exacerbations are major drivers of COPD deterioration. However, limited data are available for the 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. PMID:27143869

  18. 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.)

  19. 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...

  20. 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

  1. 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

  2. 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.)

  3. 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.

  4. Blood Eosinophils and Exacerbations in Chronic Obstructive Pulmonary Disease

    DEFF Research Database (Denmark)

    Vedel-Krogh, Signe; Nielsen, Sune F; Lange, Peter;

    2016-01-01

    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...... and 2,864 moderate COPD exacerbations were recorded. Among all participants with COPD, blood eosinophils above versus below 0.34∙10(9) cells/L had a multivariable adjusted incidence rate ratio of 1.76 (95%CI: 1.56-1.99) for severe exacerbations and of 1.15 (1.05-1.27) for moderate exacerbations...

  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. 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.

  7. Co-exposure to polycyclic aromatic hydrocarbons, benzene and toluene and their dose-effects on oxidative stress damage in kindergarten-aged children in Guangzhou, China.

    Science.gov (United States)

    Li, Junnan; Lu, Shaoyou; Liu, Guihua; Zhou, Yuanxiu; Lv, Yanshan; She, Jianwen; Fan, Ruifang

    2015-08-15

    Polycyclic aromatic hydrocarbons (PAHs), benzene and toluene (BT) are ubiquitous toxic pollutants in the environment. Children are sensitive and susceptible to exposure to these contaminants. To investigate the potential oxidative DNA damage from the co-exposure of PAHs and BT in children, 87 children (aged 3-6) from a kindergarten in Guangzhou, China, were recruited. Ten urinary PAHs and four BT metabolites, as well as 8-hydroxy-2'-deoxyguanosine (8-OHdG, a biomarker of oxidative DNA damage)in urine, were determined using a liquid chromatography tandem mass spectrometer. The results demonstrated that the levels of PAHs and BT in children from Guangzhou were 2-30 times higher than those in children from the other countries based on a comparison with recent data from the literature. In particular, the difference is more substantial for pyrene and volatile BT. Co-exposure to PAHs and BT could lead to additive oxidative DNA damage. Significant dose-effects were observed between the sum concentration of urinary monohydroxylated metabolites of PAHs (∑OH-PAHs), the sum concentration of the metabolites of BT (∑BT) and 8-OHdG levels. Every one percent increase in urinary PAHs and BT generated 0.33% and 0.02% increases in urinary 8-OHdG, respectively. We also determined that the urinary levels of PAHs and BT were negatively associated with the age of the children. Moreover, significant differences in the levels of ∑OH-PAHs and ∑BT were determined between 3- and 6-year-old children (pinhalation frequencies. In conclusion, exposure to PAHs or BT could lead to oxidative DNA damage, and 8-OHdG is a good biomarker for indicating the presence of DNA damage. There exists a significant dose-effect relationship between PAH exposure, BT exposure and the concentration of 8-OHdG in urine. Toddlers (3-4 years old) face a higher burden of PAH and BT exposure compared with older children.

  8. 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

  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. 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. 

  11. 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

  12. Expression of human complement factor H prevents age-related macular degeneration-like retina damage and kidney abnormalities in aged Cfh knockout mice.

    Science.gov (United States)

    Ding, Jin-Dong; Kelly, Una; Landowski, Michael; Toomey, Christopher B; Groelle, Marybeth; Miller, Chelsey; Smith, Stephanie G; Klingeborn, Mikael; Singhapricha, Terry; Jiang, Haixiang; Frank, Michael M; Bowes Rickman, Catherine

    2015-01-01

    Complement factor H (CFH) is an important regulatory protein in the alternative pathway of the complement system, and CFH polymorphisms increase the genetic risk of age-related macular degeneration dramatically. These same human CFH variants have also been associated with dense deposit disease. To mechanistically study the function of CFH in the pathogenesis of these diseases, we created transgenic mouse lines using human CFH bacterial artificial chromosomes expressing full-length human CFH variants and crossed these to Cfh knockout (Cfh(-/-)) mice. Human CFH protein inhibited cleavage of mouse complement component 3 and factor B in plasma and in retinal pigment epithelium/choroid/sclera, establishing that human CFH regulates activation of the mouse alternative pathway. One of the mouse lines, which express relatively higher levels of CFH, demonstrated functional and structural protection of the retina owing to the Cfh deletion. Impaired visual function, detected as a deficit in the scotopic electroretinographic response, was improved in this transgenic mouse line compared with Cfh(-/-) mice, and transgenics had a thicker outer nuclear layer and less sub-retinal pigment epithelium deposit accumulation. In addition, expression of human CFH also completely protected the mice from developing kidney abnormalities associated with loss of CFH. These humanized CFH mice present a valuable model for study of the molecular mechanisms of age-related macular degeneration and dense deposit disease and for testing therapeutic targets.

  13. 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

  14. Intense inflammation and nerve damage in early multiple sclerosis subsides at older age: a reflection by cerebrospinal fluid biomarkers.

    Directory of Open Access Journals (Sweden)

    Mohsen Khademi

    Full Text Available Inflammatory mediators have crucial roles in leukocyte recruitment and subsequent central nervous system (CNS neuroinflammation. The extent of neuronal injury and axonal loss are associated with the degree of CNS inflammation and determine physical disability in multiple sclerosis (MS. The aim of this study was to explore possible associations between a panel of selected cerebrospinal fluid biomarkers and robust clinical and demographic parameters in a large cohort of patients with MS and controls (n = 1066 using data-driven multivariate analysis. Levels of matrix metalloproteinase 9 (MMP9, chemokine (C-X-C motif ligand 13 (CXCL13, osteopontin (OPN and neurofilament-light chain (NFL were measured by ELISA in 548 subjects comprising different MS subtypes (relapsing-remitting, secondary progressive and primary progressive, clinically isolated syndrome and persons with other neurological diseases with or without signs of inflammation/infection. Principal component analyses and orthogonal partial least squares methods were used for unsupervised and supervised interrogation of the data. Models were validated using data from a further 518 subjects in which one or more of the four selected markers were measured. There was a significant association between increased patient age and lower levels of CXCL13, MMP9 and NFL. CXCL13 levels correlated well with MMP9 in the younger age groups, but less so in older patients, and after approximately 54 years of age the levels of CXCL13 and MMP9 were consistently low. CXCL13 and MMP9 levels also correlated well with both NFL and OPN in younger patients. We demonstrate a strong effect of age on both inflammatory and neurodegenerative biomarkers in a large cohort of MS patients. The findings support an early use of adequate immunomodulatory disease modifying drugs, especially in younger patients, and may provide a biological explanation for the relative inefficacy of such treatments in older patients at later

  15. 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

  16. Mechanical damage of red blood cells by rotary blood pumps: selective destruction of aged red blood cells and subhemolytic trauma.

    Science.gov (United States)

    Sakota, Daisuke; Sakamoto, Ryuki; Sobajima, Hideo; Yokoyama, Naoyuki; Waguri, Satoshi; Ohuchi, Katsuhiro; Takatani, Setsuo

    2008-10-01

    In this study, mean cell volume (MCV), mean cell hemoglobin concentration (MCHC), and mean cell hemoglobin (MCH) were measured to quantify RBC damage by rotary blood pumps. Six-hour hemolysis tests were conducted with a Bio-pump BPX-80, a Sarns 15200 roller pump, and a prototype mag-lev centrifugal pump (MedTech Heart) using fresh porcine blood circulated at 5 L/min against a 100 mm Hg head pressure. The temperature of the test and noncirculated control blood was maintained at 37 degrees C. The normalized index of hemolysis (NIH) of each pump was determined by measuring the plasma-free hemoglobin level. The MCV was measured with a Coulter counter, and MCHC was derived from total hemoglobin and hematocrit. MCH was derived from MCV and MCHC. A multivariance statistical analysis (ANOVA) revealed statistically significant differences (n = 15, P < 0.05) in MCV, MCHC, and MCH between the blood sheared by the rotary blood pumps and the nonsheared control blood. Normalized to the control blood, the Bio-pump BPX-80 showed an MCV of 1.04 +/- 0.03, an MCHC of 0.95 +/- 0.04, and an MCH of 0.98 +/- 0.02; the mag-lev MedTech Heart had an MCV of 1.02 +/- 0.02, an MCHC of 0.97 +/- 0.02, and an MCH of 0.99 +/- 0.01; and the roller pump exhibited an MCV of 1.03 +/- 0.03, an MCHC of 0.96 +/- 0.03, and an MCH of 0.99 +/- 0.01. Per 0.01 increase in NIH, the BPX-80 showed a normalized MCV change of +10.1% and a normalized MCHC change of -14.0%; the MedTech Heart demonstrated a +6.9% MCV and -9.5% MCHC change; and the roller pump had a +0.5% MCV and -0.6% MCHC change. Due to shear in the pump circuits, the RBC increased while the MCHC decreased. The likely mechanism is that older RBCs with smaller size and higher hemoglobin concentration were destroyed fast by the shear, leaving younger RBCs with larger size and lower hemoglobin concentration. Subhemolytic trauma caused the intracellular hemoglobin to decrease due to gradual hemoglobin leakage through the micropores formed in the thinned

  17. 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

  18. Assessing Treatment Effects of Inhaled Corticosteroids on Medical Expenses and Exacerbations among COPD Patients: Longitudinal Analysis of Managed Care Claims

    Science.gov (United States)

    Akazawa, Manabu; Stearns, Sally C; Biddle, Andrea K

    2008-01-01

    Objective To assess costs, effectiveness, and cost-effectiveness of inhaled corticosteroids (ICS) augmenting bronchodilator treatment for chronic obstructive pulmonary disease (COPD). Data Sources Claims between 1997 and 2005 from a large managed care database. Study Design Individual-level, fixed-effects regression models estimated the effects of initiating ICS on medical expenses and likelihood of severe exacerbation. Bootstrapping provided estimates of the incremental cost per severe exacerbation avoided. Data Extraction Methods COPD patients aged 40 or older with ≥15 months of continuous eligibility were identified. Monthly observations for 1 year before and up to 2 years following initiation of bronchodilators were constructed. Principal Findings ICS treatment reduced monthly risk of severe exacerbation by 25 percent. Total costs with ICS increased for 16 months, but declined thereafter. ICS use was cost saving 46 percent of the time, with an incremental cost-effectiveness ratio of $2,973 per exacerbation avoided; for patients ≥50 years old, ICS was cost saving 57 percent of time. Conclusions ICS treatment reduces exacerbations, with an increase in total costs initially for the full sample. Compared with younger patients with COPD, patients aged 50 or older have reduced costs and improved outcomes. The estimated cost per severe exacerbation avoided, however, may be high for either group because of uncertainty as reflected by the large standard errors of the parameter estimates. PMID:18671750

  19. 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

  20. 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

  1. 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.

  2. 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.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    -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...... definition of exacerbations was robust and without major biases. CONCLUSIONS: Compared to individuals with GOLD 1, the risk of exacerbations was 17-fold for GOLD 4, 5-fold for GOLD 3, and 2-fold for GOLD 2. Medically treated exacerbations defined by register linkage seem a valid, robust, and low......,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...

  4. Is respiratory viral infection really an important trigger of asthma exacerbations in children?

    Science.gov (United States)

    Lee, So-lun; Chiu, Shui-seng Susan; Malik, Peiris Joseph S; Chan, Kwok-hung; Wong, Hing-sang Wilfred; Lau, Yu-lung

    2011-10-01

    We performed a prospective cohort study from September 2003 to December 2004 to delineate attributing the effect of different respiratory viral infections including newly discovered ones to asthma exacerbations in children in Hong Kong. One hundred and fourteen children aged 6-14 years with chronic stable asthma and on regular inhaled steroid were monitored for respiratory symptoms over a full calendar year from recruitment. They would attend the study clinic if peak expiratory flow rate decreased to below 80% of their baselines, if they met a predefined symptom score, or if parents subjectively felt them developing a cold. Virological diagnosis using virus culture, antigen detection, and polymerase chain reaction methods on nasal swab specimens would be attempted for all these visits irrespective of triggers. Physician diagnosed outcome of each episode was documented. Three hundred and five episodes of respiratory illnesses were captured in the cohort. Nasal specimens were available in 166 episodes, 92 of which were diagnosed as asthma exacerbations, and 74 non-asthma related episodes. Respiratory viruses were detected in 61 of 166 episodes (36.7%). There was no significant difference in virus detection rate between asthma exacerbations (32 out of 97 episodes, 34.8%) and non-asthma respiratory illnesses (29 out of 79 episodes, 39.2%). Although newly discovered respiratory viruses were identified in these episodes, rhinovirus was the commonest organism associated with both asthma exacerbations and non-asthma related episodes. Plausible explanations for much lower virus detection rate than previously reported include improved personal hygiene and precautionary measures taken during respiratory tract infections in the immediate post-severe acute respiratory syndrome period together with a significant contribution of other adverse factors like environmental air pollution. We conclude that not all viral infections in children with asthma lead to an asthma exacerbation

  5. The Effects of Smoking Cessation on the Risk of Chronic Obstructive Pulmonary Disease Exacerbations

    Science.gov (United States)

    Bryson, Christopher L.; Chien, Jason W.; Sun, Haili; Udris, Edmunds M.; Evans, Laura E.; Bradley, Katharine A.

    2009-01-01

    BACKGROUND Smoking cessation has been demonstrated to reduce the rate of loss of lung function and mortality among patients with mild to moderate chronic obstructive pulmonary disease (COPD). There is a paucity of evidence about the effects of smoking cessation on the risk of COPD exacerbations. OBJECTIVE We sought to examine whether smoking status and the duration of abstinence from tobacco smoke is associated with a decreased risk of COPD exacerbations. DESIGN We assessed current smoking status and duration of smoking abstinence by self-report. Our primary outcome was either an inpatient or outpatient COPD exacerbation. We used Cox regression to estimate the risk of COPD exacerbation associated with smoking status and duration of smoking cessation. PARTICIPANTS We performed a cohort study of 23,971 veterans who were current and past smokers and had been seen in one of seven Department of Veterans Affairs (VA) primary care clinics throughout the US. MEASUREMENTS AND MAIN RESULTS In comparison to current smokers, ex-smokers had a significantly reduced risk of COPD exacerbation after adjusting for age, comorbidity, markers of COPD severity and socio-economic status (adjusted HR 0.78, 95% CI 0.75–0.87). The magnitude of the reduced risk was dependent on the duration of smoking abstinence (adjusted HR: quit <1 year, 1.04; 95% CI 0.87–1.26; 1–5 years 0.93, 95% CI 0.79–1.08; 5–10 years 0.84, 95% CI 0.70–1.00; ≥10 years 0.65, 95% CI 0.58–0.74; linear trend <0.001). CONCLUSIONS Smoking cessation is associated with a reduced risk of COPD exacerbations, and the described reduction is dependent upon the duration of abstinence. PMID:19194768

  6. Aging-related expression of inducible nitric oxide synthase and markers of tissue damage in the rat penis.

    Science.gov (United States)

    Ferrini, M; Magee, T R; Vernet, D; Rajfer, J; González-Cadavid, N F

    2001-03-01

    Erectile dysfunction in the aging male results in part from the loss of compliance of the corpora cavernosal smooth muscle due to the progressive replacement of smooth muscle cells by collagen fibers. We have examined the hypothesis that a spontaneous local induction of inducible nitric oxide synthase (iNOS) expression and the subsequent peroxynitrite formation occurs in the penis during aging and that this process is accompanied by a stimulation of smooth muscle apoptosis and collagen deposition. The penile shaft and crura were excised from young (3-5 mo old) and old (24-30 mo old) rats, with or without perfusion with 4% formalin. Fresh tissue was used for iNOS and proteasome 2C mRNA determinations by reverse transcription polymerase chain reaction assay, ubiquitin mRNA by Northern blot, and iNOS protein by Western blot. Penile sections from perfused animals were embedded in paraffin and immunostained with antibodies against iNOS and nitrotyrosine, submitted to the TUNEL assay for apoptosis, or stained for collagen, followed by image analysis quantitation. A 4.1-fold increase in iNOS mRNA was observed in the old versus young tissues, paralleled by a 4.9-fold increase in iNOS protein. The proteolysis marker, ubiquitin, was increased 1.9-fold, whereas a related gene, proteasome 2c, was not significantly affected. iNOS immunostaining was increased 3.6-fold in the penile smooth muscle of the old rats as compared with the young rats. The peroxynitrite indicator nitrotyrosine was increased by 1.6-fold, accompanied by a 3.6-fold increase in apoptotic cells and a 2.0-fold increase in collagen fibers in the old penis. In conclusion, aging in the penis is accompanied by an induction of iNOS and peroxynitrite formation that may lead to the observed increase in apoptosis and proteolysis and may counteract a higher rate of collagen deposition in the old penis.

  7. Viral Profile of COPD Exacerbations According to Patients§

    Science.gov (United States)

    Dimopoulos, G; Tsiodras, S; Lerikou, M; Chranioti, Aik; Perros, E; Anagnostopoulou, U; Karakitsos, P; Armaganidis, A

    2015-01-01

    Background : To compare the differences between elderly and non-elderly patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) due to viral infections. Methods : Patients with chronic obstructive pulmonary disease (COPD) exacerbation were recruited and classified as elderly (>65 years) and non-elderly (≤ 65 years). Sputum and oropharyngeal samples were assessed, PCR for respiratory viruses and cultures for common pathogens were performed. Results : 247 patients (median age: 69.3±9.5 years) were recruited and categorized into group A: non-elderly patients [n=81 (32.8%), median age 58±5.99] and group B: elderly patients [n=166 (67.2%), median age 74.8±4.8] years. In 133 (53.8%) patients a viral infection was identified and in 34 (13.8%) a bacterial pathogen was isolated from cultures. In 18 (7.3%) patients a double infection (bacterial+viral) was identified. In group B, the presence of cardiac failure (46.6% vs 28.3%, p<0.001), renal failure (10.5% vs 4%, p=0.03), bacterial co-infection (13.8% vs 7.4%, p=0.04), influenza vaccination rates (45.5% vs 215, p<0.001), and longer hospital stay (8.4±4.4 vs 7.5±3.2 days, p=0.02) were higher than group A. The overall rate of viral infections did not differ according to age. A trend to higher rates of infection with parainfluenza 3 [19 (20%) patients in group B vs3 (7.5%) patients in group A, p=0.04] was observed in older patients. Conclusion : No differences on the rate and type of viral infections were noted for elderly vs non elderly patients. However, they tended to have more bacterial co-infections that led to AECOPD and longer hospitalization stays compared to non-elderly patients. PMID:25741393

  8. 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.

  9. 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

  10. 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

  11. Calcium Channel Blockers and Esophageal Sclerosis: Should We Expect Exacerbation of Interstitial Lung Disease

    Directory of Open Access Journals (Sweden)

    Charalampos Seretis

    2012-01-01

    Full Text Available Esophageal sclerosis is the most common visceral manifestation of systemic sclerosis, resulting in impaired esophageal clearance and retention of ingested food; in addition, co-existence of lung fibrosis with esophageal scleroderma is not uncommon. Both the progression of generalized connective tissue disorders and the damaging effect of chronic aspiration due to esophageal dysmotility appear to be involved in this procedure of interstitial fibrosis. Nifedipine is a widely prescribed calcium antagonist in a significant percentage of rheumatologic patients suffering from Raynaud syndrome, in order to inhibit peripheral vasospasm. Nevertheless, blocking calcium channels has proven to contribute to exacerbation of gastroesophageal reflux, which consequently can lead to chronic aspiration. We describe the case of severe exacerbation of interstitial lung disease in a 76-year-old female with esophageal sclerosis who was treated with oral nifedipine for Raynaud syndrome.

  12. 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

  13. 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

  14. 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.

  15. 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

  16. 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

  17. 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...

  18. 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...... during pregnancy....

  19. 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.

  20. 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...

  1. [Exacerbations of asthma--precipitating factors: drugs].

    Science.gov (United States)

    Sanfiorenzo, C; Pipet, A

    2011-10-01

    Asthmatic exacerbations are sometimes triggered by medications, primarily the non-steroidal anti-inflammatory agents (NSAIDS) and beta-blockers. Asthma attacks induced by NSAIDS occur rapidly and can be severe. Widal syndrome is a specific disease entity whose physiopathology remains incompletely explained. Asthma is characteristically severe and steroid dependent; desensitisation with aspirin has been proposed, but this remains controversial. Beta-blockers are contra-indicated in asthma; the β1 "cardioselectivity" of some agents is not absolute, disappearing at high doses and the "partial agonists" are not better tolerated. However, certain authors have called into question the harmful effect of beta-blockade in moderate and stable asthma. More studies are needed, but the current data suggest that in some cases beta-blockers may be safe but their use requires close supervision. Other molecules can pose problems in asthmatics (dipyridamole, synthetic sex hormones and certain excipients). On the whole, there has been little innovation concerning the hazard that drugs can pose for some asthmatics. The task for the future will be to specify the physiopathology of Widal syndrome, and to clarify the categories of patients in whom beta-blockers can be safely employed as the public health consequences of cardiovascular pathologies make this an important issue for lung specialists.

  2. 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

  3. 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.

  4. 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.

  5. 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...

  6. 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.

  7. 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...

  8. 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.

  9. 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.

  10. 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...

  11. 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

  12. 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...

  13. Airway microbiome dynamics in exacerbations of chronic obstructive pulmonary disease.

    Science.gov (United States)

    Huang, Yvonne J; Sethi, Sanjay; Murphy, Timothy; Nariya, Snehal; Boushey, Homer A; Lynch, Susan V

    2014-08-01

    Specific bacterial species are implicated in the pathogenesis of exacerbations of chronic obstructive pulmonary disease (COPD). However, recent studies of clinically stable COPD patients have demonstrated a greater diversity of airway microbiota, whose role in acute exacerbations is unclear. In this study, temporal changes in the airway microbiome before, at the onset of, and after an acute exacerbation were examined in 60 sputum samples collected from subjects enrolled in a longitudinal study of bacterial infection in COPD. Microbiome composition and predicted functions were examined using 16S rRNA-based culture-independent profiling methods. Shifts in the abundance (≥ 2-fold, P microbiome could be useful indicators of exacerbation development or outcome.

  14. 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...

  15. Determinants of change in physical activity during moderate-to-severe COPD exacerbation

    Science.gov (United States)

    Esteban, Cristóbal; Quintana, José M; Garcia-Gutierrez, Susana; Anton-Ladislao, Ane; Gonzalez, Nerea; Baré, Marisa; Fernández de Larrea, Nerea; Rivas-Ruiz, Francisco

    2016-01-01

    Background Data are scarce on patient physical activity (PA) level during exacerbations of chronic obstructive pulmonary disease (eCOPD). The objective of the study was to evaluate the level and determinants of change in PA during an eCOPD. Materials and methods We conducted a prospective cohort study with recruitment from emergency departments (EDs) of 16 participating hospitals from June 2008 to September 2010. Data were recorded on socioeconomic characteristics, dyspnea, forced expiratory volume in 1 second (FEV1%), comorbidities, health-related quality of life, factors related to exacerbation, and PA in a stable clinical condition and during the eCOPD episode. Results We evaluated 2,487 patients. Common factors related to the change in PA during hospital admission or 7 days after discharge to home from the ED were lower PA at baseline and during the first 24 hours after the index evaluation. Age, quality of life, living alone, length of hospital stay, and use of anticholinergic or systemic corticosteroids in treating the exacerbation were associated with the change in PA among hospitalized patients. Predictors of change among patients not admitted to hospital were baseline FEV1% and dyspnea at rest on ED arrival. Conclusion Among the patients evaluated in an ED for an eCOPD, the level and change in PA was markedly variable. Factors associated with exacerbation (PA 24 hours after admission, medication during admission, and length of hospital stay) and variables reflecting patients’ stable clinical condition (low level of PA, age, quality of life, FEV1%) are predictors of the change in PA during a moderate-to-severe eCOPD. PMID:26893555

  16. 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...

  17. 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...

  18. The Sputum Microbiome in Chronic Obstructive Pulmonary Disease Exacerbations.

    Science.gov (United States)

    Huang, Yvonne J; Boushey, Homer A

    2015-11-01

    Acute exacerbations of chronic obstructive pulmonary disease (COPD) are thought to be associated with--and perhaps to mediate--accelerated loss of lung function in COPD. Although the application of culture-independent methods for detection of bacteria have shown COPD to be associated with marked differences in the burden, diversity, and composition of the bronchial bacterial microbiome, few studies have examined the changes associated with community-acquired exacerbations of the disease. In a longitudinal cohort study of COPD, the availability of sputum samples from subjects obtained at the onset of an exacerbation and during periods of clinical stability before and after the event enabled us to recently address this gap in knowledge, using culture-independent, 16S rRNA-based analysis methods combined with in silico inference of metagenomic functions. We observed sputum bacterial composition to be generally stable over the preexacerbation period of clinical stability, but to change at the time of exacerbation, with specific enrichment in not only typical COPD-associated bacterial species (e.g., Haemophilus influenzae) but also other phylogenetically related species with pathogenic potential. Concurrently, we observed depleted abundance of other bacteria whose predicted metagenomes suggest functional capacities to produce a variety of antiinflammatory compounds. Most strikingly, we found that resolution of these exacerbation-related changes in sputum microbiota composition differed significantly, depending on the exacerbation treatments prescribed. Treatment with corticosteroids resulted in microbiome enrichment for a number of bacterial communities, mostly members of the Proteobacteria phylum, whereas prolonged suppression of microbiota was seen in those treated with antibiotics alone. Taken together, our findings suggest that exacerbations of COPD are associated with heterogeneous changes in the bronchial microbiome, with increases in the abundance of species

  19. 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 ...

  20. 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 ...

  1. 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...

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

    DEFF Research Database (Denmark)

    Ringbaek, T.; Lange, P.; Mogensen, T.;

    2008-01-01

    Acute exacerbation of COPD is a major cause of hospitalisation in Denmark. Most of the patients require supplemental oxygen in the acute phase and some patients continue oxygen therapy at home after discharge. In this paper we discuss the physiological mechanisms of respiratory failure seen...... in acute exacerbations of COPD. The principles for oxygen therapy in the acute phase are described and recommendations for oxygen therapy are suggested Udgivelsesdato: 2008/5/5...

  3. The causes and consequences of seasonal variation in COPD exacerbations

    Directory of Open Access Journals (Sweden)

    Donaldson GC

    2014-10-01

    Full Text Available Gavin C Donaldson, Jadwiga A Wedzicha Airways Disease Section, National Heart and Lung Institute, Imperial College London, London, UK Abstract: The time of year when patients experience exacerbations of chronic obstructive pulmonary disease is a much-overlooked feature of the disease. The higher incidence of exacerbations in winter has important consequences for patients in terms of increased morbidity and mortality. The seasonality also imposes a considerable burden on already-overloaded health care services, with both primary care consultations and hospital admissions increasing in number. The seasonality of exacerbations varies with latitude, and is greater in more temperate climates, where there may be less protection from outdoor and indoor cold exposure. The precise causes of the seasonality are unknown, but thought to be partly due to the increased prevalence of respiratory viral infections circulating in cold, damp conditions. Increased susceptibility to viral infection may also be a mechanism mediated through increased airway inflammation or possibly reduced vitamin D levels. The seasonality of exacerbations informs us about the triggers of exacerbations and suggests possible strategies to reduce their number. Keywords: exacerbations of COPD, seasonality, winter mortality, winter morbidity

  4. Circulating level of microRNA-126 may be a potential biomarker for recovery from smoking-related vascular damage in middle-aged habitual smokers

    Directory of Open Access Journals (Sweden)

    Tomonori Sugiura

    2015-06-01

    Conclusions: Endothelial damage was improved and plasma levels of circulating miR-126 were increased after 8 weeks of smoking cessation. These findings suggested a potential use of miR-126 as a biomarker for recovery from smoking-induced vascular damage.

  5. 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

  6. 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

  7. 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

  8. Moxifloxacin versus amoxicillin/clavulanic acid in outpatient acute exacerbations of COPD: MAESTRAL results.

    Science.gov (United States)

    Wilson, Robert; Anzueto, Antonio; Miravitlles, Marc; Arvis, Pierre; Alder, Jeff; Haverstock, Daniel; Trajanovic, Mila; Sethi, Sanjay

    2012-07-01

    Bacterial infections causing acute exacerbations of chronic obstructive pulmonary disease (AECOPD) frequently require antibacterial treatment. More evidence is needed to guide antibiotic choice. The Moxifloxacin in Acute Exacerbations of Chronic Bronchitis TriaL (MAESTRAL) was a multiregional, randomised, double-blind non-inferiority outpatient study. Patients were aged ≥ 60 yrs, with an Anthonisen type I exacerbation, a forced expiratory volume in 1 s clavulanic acid 875/125 mg p.o. b.i.d. (7 days). The primary end-point was clinical failure 8 weeks post-therapy in the per protocol population. Moxifloxacin was noninferior to amoxicillin/clavulanic acid at the primary end-point (111 (20.6%) out of 538, versus 114 (22.0%) out of 518, respectively; 95% CI -5.89-3.83%). In patients with confirmed bacterial AECOPD, moxifloxacin led to significantly lower clinical failure rates than amoxicillin/clavulanic acid (in the intent-to-treat with pathogens, 62 (19.0%) out of 327 versus 85 (25.4%) out of 335, respectively; p=0.016). Confirmed bacterial eradication at end of therapy was associated with higher clinical cure rates at 8 weeks post-therapy overall (p=0.0014) and for moxifloxacin (p=0.003). Patients treated with oral corticosteroids had more severe disease and higher failure rates. The MAESTRAL study showed that moxifloxacin was as effective as amoxicillin/clavulanic acid in the treatment of outpatients with AECOPD. Both therapies were well tolerated.

  9. 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

  10. 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

  11. 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 ...

  12. Determinants of change in physical activity during moderate-to-severe COPD exacerbation

    Directory of Open Access Journals (Sweden)

    Esteban C

    2016-02-01

    Full Text Available Cristóbal Esteban,1,2 José M Quintana,2,3 Susana Garcia-Gutierrez,2,3 Ane Anton-Ladislao,3 Nerea Gonzalez,2,3 Marisa Baré,2,4 Nerea Fernández de Larrea,2,5 Francisco Rivas-Ruiz2,6 For the IRYSS-COPD group 1Respiratory Department, Hospital Galdakao-Usansolo, Bizkaia; 2Red de Investigación en Servicios Sanitarios y Enfermedades Crónicas (REDISSEC, Galdakao; 3Research Unit, Hospital Galdakao-Usansolo, Bizkaia; 4Unit of Clinical Epidemiology, Corporacio Parc Tauli, Barcelona; 5Health Department, Madrid; 6Research Unit, Hospital Costa del Sol, Mabella, Málaga, Spain Background: Data are scarce on patient physical activity (PA level during exacerbations of chronic obstructive pulmonary disease (eCOPD. The objective of the study was to evaluate the level and determinants of change in PA during an eCOPD. Materials and methods: We conducted a prospective cohort study with recruitment from emergency departments (EDs of 16 participating hospitals from June 2008 to September 2010. Data were recorded on socioeconomic characteristics, dyspnea, forced expiratory volume in 1 second (FEV1%, comorbidities, health-related quality of life, factors related to exacerbation, and PA in a stable clinical condition and during the eCOPD episode. Results: We evaluated 2,487 patients. Common factors related to the change in PA during hospital admission or 7 days after discharge to home from the ED were lower PA at baseline and during the first 24 hours after the index evaluation. Age, quality of life, living alone, length of hospital stay, and use of anticholinergic or systemic corticosteroids in treating the exacerbation were associated with the change in PA among hospitalized patients. Predictors of change among patients not admitted to hospital were baseline FEV1% and dyspnea at rest on ED arrival. Conclusion: Among the patients evaluated in an ED for an eCOPD, the level and change in PA was markedly variable. Factors associated with exacerbation (PA 24 hours

  13. 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.

  14. Predicting frequent asthma exacerbations using blood eosinophil count and other patient data routinely available in clinical practice

    Directory of Open Access Journals (Sweden)

    Price D

    2016-01-01

    Full Text Available David Price,1,2 Andrew M Wilson,3 Alison Chisholm,4 Anna Rigazio,2 Anne Burden,2 Michael Thomas,5 Christine King2 1Centre for Academic Primary Care, The Institute of Applied Health Sciences, University of Aberdeen, Aberdeen, 2Research in Real-Life, Cambridge, 3Norwich Medical School, University of East Anglia, Norwich, 4Respiratory Effectiveness Group, Cambridge, 5Primary Medical Care, University of Southampton, Southampton, UK Purpose: Acute, severe asthma exacerbations can be difficult to predict and thus prevent. Patients who have frequent exacerbations are of particular concern. Practical exacerbation predictors are needed for these patients in the primary-care setting. Patients and methods: Medical records of 130,547 asthma patients aged 12–80 years from the UK Optimum Patient Care Research Database and Clinical Practice Research Datalink, 1990–2013, were examined for 1 year before (baseline and 1 year after (outcome their most recent blood eosinophil count. Baseline variables predictive (P<0.05 of exacerbation in the outcome year were compared between patients who had two or more exacerbations and those who had no exacerbation or only one exacerbation, using uni- and multivariable logistic regression models. Exacerbation was defined as asthma-related hospital attendance/admission (emergency or inpatient or acute oral corticosteroid (OCS course. Results: Blood eosinophil count >400/µL (versus ≤400/µL increased the likelihood of two or more exacerbations >1.4-fold (odds ratio [OR]: 1.48 (95% confidence interval [CI]: 1.39, 1.58; P<0.001. Variables that significantly increased the odds by up to 1.4-fold included increasing age (per year, female gender (versus male, being overweight or obese (versus normal body mass index, being a smoker (versus nonsmoker, having anxiety/depression, diabetes, eczema, gastroesophageal reflux disease, or rhinitis, and prescription for acetaminophen or nonsteroidal anti-inflammatory drugs. Compared with

  15. A Review of the Bender Gestalt Test as a Screening Instrument for Brain Damage with School-Aged Children of Normal Intelligence Since 1970.

    Science.gov (United States)

    Eno, Larry; Deichmann, John

    1980-01-01

    All methods reviewed significantly discriminate between groups of brain damaged and unimpaired children. No method, however, provides successful predictive rates high enough to warrant the use of the Bender as the sole diagnostic instrument in individual cases. (Author)

  16. Non-diabetic hyperglycemia exacerbates disease severity in Mycobacterium tuberculosis infected guinea pigs.

    Science.gov (United States)

    Podell, Brendan K; Ackart, David F; Kirk, Natalie M; Eck, Sarah P; Bell, Christopher; Basaraba, Randall J

    2012-01-01

    Hyperglycemia, the diagnostic feature of diabetes also occurs in non-diabetics associated with chronic inflammation and systemic insulin resistance. Since the increased risk of active TB in diabetics has been linked to the severity and duration of hyperglycemia, we investigated what effect diet-induced hyperglycemia had on the severity of Mycobacterium tuberculosis (Mtb) infection in non-diabetic guinea pigs. Post-prandial hyperglycemia was induced in guinea pigs on normal chow by feeding a 40% sucrose solution daily or water as a carrier control. Sucrose feeding was initiated on the day of aerosol exposure to the H37Rv strain of Mtb and continued for 30 or 60 days of infection. Despite more severe hyperglycemia in sucrose-fed animals on day 30, there was no significant difference in lung bacterial or lesion burden until day 60. However the higher spleen and lymph node bacterial and lesion burden at day 30 indicated earlier and more severe extrapulmonary TB in sucrose-fed animals. In both sucrose- and water-fed animals, serum free fatty acids, important mediators of insulin resistance, were increased by day 30 and remained elevated until day 60 of infection. Hyperglycemia mediated by Mtb infection resulted in accumulation of advanced glycation end products (AGEs) in lung granulomas, which was exacerbated by sucrose feeding. However, tissue and serum AGEs were elevated in both sucrose and water-fed guinea pigs by day 60. These data indicate that Mtb infection alone induces insulin resistance and chronic hyperglycemia, which is exacerbated by sucrose feeding. Moreover, Mtb infection alone resulted in the accumulation tissue and serum AGEs, which are also central to the pathogenesis of diabetes and diabetic complications. The exacerbation of insulin resistance and hyperglycemia by Mtb infection alone may explain why TB is more severe in diabetics with poorly controlled hyperglycemia compared to non-diabetics and patients with properly controlled blood glucose levels.

  17. Non-diabetic hyperglycemia exacerbates disease severity in Mycobacterium tuberculosis infected guinea pigs.

    Directory of Open Access Journals (Sweden)

    Brendan K Podell

    Full Text Available Hyperglycemia, the diagnostic feature of diabetes also occurs in non-diabetics associated with chronic inflammation and systemic insulin resistance. Since the increased risk of active TB in diabetics has been linked to the severity and duration of hyperglycemia, we investigated what effect diet-induced hyperglycemia had on the severity of Mycobacterium tuberculosis (Mtb infection in non-diabetic guinea pigs. Post-prandial hyperglycemia was induced in guinea pigs on normal chow by feeding a 40% sucrose solution daily or water as a carrier control. Sucrose feeding was initiated on the day of aerosol exposure to the H37Rv strain of Mtb and continued for 30 or 60 days of infection. Despite more severe hyperglycemia in sucrose-fed animals on day 30, there was no significant difference in lung bacterial or lesion burden until day 60. However the higher spleen and lymph node bacterial and lesion burden at day 30 indicated earlier and more severe extrapulmonary TB in sucrose-fed animals. In both sucrose- and water-fed animals, serum free fatty acids, important mediators of insulin resistance, were increased by day 30 and remained elevated until day 60 of infection. Hyperglycemia mediated by Mtb infection resulted in accumulation of advanced glycation end products (AGEs in lung granulomas, which was exacerbated by sucrose feeding. However, tissue and serum AGEs were elevated in both sucrose and water-fed guinea pigs by day 60. These data indicate that Mtb infection alone induces insulin resistance and chronic hyperglycemia, which is exacerbated by sucrose feeding. Moreover, Mtb infection alone resulted in the accumulation tissue and serum AGEs, which are also central to the pathogenesis of diabetes and diabetic complications. The exacerbation of insulin resistance and hyperglycemia by Mtb infection alone may explain why TB is more severe in diabetics with poorly controlled hyperglycemia compared to non-diabetics and patients with properly controlled

  18. Exacerbation of pathology by oxidative stress in respiratory and locomotor muscles with Duchenne muscular dystrophy.

    Science.gov (United States)

    Lawler, John M

    2011-05-01

    Duchenne muscular dystrophy (DMD) is the most devastating type of muscular dystrophy, leading to progressive weakness of respiratory (e.g. diaphragm) and locomotor muscles (e.g. gastrocnemius). DMD is caused by X-linked defects in the gene that encodes for dystrophin, a key scaffolding protein of the dystroglycan complex (DCG) within the sarcolemmal cytoskeleton. As a result of a compromised dystroglycan complex, mechanical integrity is impaired and important signalling proteins (e.g. nNOS, caveolin-3) and pathways are disrupted. Disruption of the dystroglycan complex leads to high susceptibility to injury with repeated, eccentric contractions as well as inflammation, resulting in significant damage and necrosis. Chronic damage and repair cycling leads to fibrosis and weakness. While the link between inflammation with damage and weakness in the DMD diaphragm is unresolved, elevated oxidative stress may contribute to damage, weakness and possibly fibrosis. While utilization of non-specific antioxidant interventions has yielded inconsistent results, recent data suggest that NAD(P)H oxidase could play a pivotal role in elevating oxidative stress via integrated changes in caveolin-3 and stretch-activated channels (SACs). Oxidative stress may act as an amplifier, exacerbating disruption of the dystroglycan complex, upregulation of the inflammatory transcription factor NF-B, and thus functional impairment of force-generating capacity.

  19. 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...... 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....

  20. Modulation of airway inflammation to prevent exacerbations of COPD

    Directory of Open Access Journals (Sweden)

    M. Solèr

    2005-12-01

    Full Text Available Exacerbations of chronic obstructive pulmonary disease (COPD are periods in the chronic course of this disease with symptoms of intensified inflammation, induced in part by infections but also by noninfectious irritating mechanisms. Although these exacerbations seem to be linked to accelerated long-term disease progression and impaired quality of life, there are only limited preventive measures available, apart from smoking cessation. This article compares the effectiveness of different pharmacological treatments for the prevention of COPD exacerbations, including the oral bacterial lysate OM-85. Given the differences in the mechanism of action of the treatments discussed, this opens some hope for additive or potentiating effects with combined treatments, which will have to be studied in future controlled trials.

  1. 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

  2. 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 ...

  3. 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.

  4. Can resistive breathing injure the lung? Implications for COPD exacerbations

    Directory of Open Access Journals (Sweden)

    Vassilakopoulos T

    2016-09-01

    Full Text Available Theodoros Vassilakopoulos, Dimitrios Toumpanakis Pulmonary and Critical Care Medicine, Medical School, National and Kapodistrian University of Athens, Greece Abstract: In obstructive lung diseases, airway inflammation leads to bronchospasm and thus resistive breathing, especially during exacerbations. This commentary discusses experimental evidence that resistive breathing per se (the mechanical stimulus in the absence of underlying airway inflammation leads to lung injury and inflammation (mechanotransduction. The potential implications of resistive breathing-induced mechanotrasduction in COPD exacerbations are presented along with the available clinical evidence. Keywords: resistive breathing, COPD, mechanotransduction, bronchoconstriction, inflammation

  5. Lateral pallidotomy exacerbates akinesia in the Parkinsonian patient.

    Science.gov (United States)

    Munro-Davies, L E; Gregory, R; Squires, W; Radatz, M; Silburn, P; Scott, R; Aziz, T; Stein, J F

    1999-11-01

    Despite the recent resurgence of interest in the use of pallidotomy for the treatment of Parkinson's disease, there remains considerable debate about the optimal lesion site. Although the current understanding of the neural mechanisms underlying Parkinsonism would suggest that the medial pallidum is the logical site for alleviation of symptoms, some surgeons still advocate lesions in the lateral pallidum. We report the case of such a lesion placement verified pathologically, which resulted in exacerbation of akinesia postoperatively. This demonstrates that accurate targeting in the pallidum is critical to avoid exacerbation of symptoms by lesioning the lateral pallidum.

  6. 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

  7. The nuclear retention of transcription factor FOXO3a correlates with a DNA damage response and increased glutamine synthetase expression by astrocytes suggesting a neuroprotective role in the ageing brain.

    Science.gov (United States)

    Fluteau, Adeline; Ince, Paul G; Minett, Thais; Matthews, Fiona E; Brayne, Carol; Garwood, Claire J; Ratcliffe, Laura E; Morgan, Sarah; Heath, Paul R; Shaw, Pamela J; Wharton, Stephen B; Simpson, Julie E

    2015-11-16

    The accumulation of reactive oxygen species leading to oxidative damage and cell death plays an important role in a number of neurodegenerative disorders. FOXO3a, the main isoform of FOXO transcription factors, mediates the cellular response to oxidative stress by regulating the expression of genes involved in DNA repair and glutamine metabolism, including glutamine synthetase (GS). Immunohistochemical investigation of the population-based neuropathology cohort of the Medical Research Council's Cognitive Function and Ageing Study (MRC CFAS) demonstrates that nuclear retention of FOXO3a significantly correlates with a DNA damage response and with GS expression by astrocytes. Furthermore, we show that GS expression correlates with increasing Alzheimer-type pathology in this ageing cohort. Our findings suggest that in response to oxidative stress, the nuclear retention of FOXO3a in astrocytes upregulates expression of GS as a neuroprotective mechanism. However, the activity of GS may be compromised by increasing levels of oxidative stress in the ageing brain resulting in dysfunctional enzyme activity, neuronal excitotoxic damage and cognitive impairment.

  8. 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

  9. 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...

  10. 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

  11. 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…

  12. Disruption of cyclooxygenase type 2 exacerbates apoptosis and renal damage during obstructive nephropathy

    DEFF Research Database (Denmark)

    Nilsson, Line; Madsen, Kirsten; Krag, Søren Rasmus Palmelund;

    2015-01-01

    Renal oxidative stress is increased in response to ureteral obstruction. In vitro, cyclooxygenase (COX)-2 activity contributes to protection against oxidants. In the present study, we tested the hypothesis that COX-2 activity counters oxidative stress and apoptosis in an in vivo model...

  13. 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.

  14. 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

  15. The peculiarities of the metabolism processes in patients with the exacerbation of extensive psoriasis

    Directory of Open Access Journals (Sweden)

    Baityakov V. V.

    2011-09-01

    Full Text Available Purpose. The study of some indices of the metabolism in patients with the exacerbation of extensive psoriasis, the investigation of the revealed disorder dependence on the clinical peculiarities of the disease and anamnesis data. Methods. 253 patients with extensive psoriasis from the age of 18 to 72 have been investigated.Some indices of lipid and protein metabolism, medium molecular peptide content, lipid peroxidation and antioxidant protection processes in blood plasma have been studied. Results. Dysproteinemia, the increase of С — reactive protein level, seromucoid, medium molecular peptides, common lipids, triglycerides, the reduction of the level of lipid proteins of high density, the intensification of lipid peroxidation processes and the reduction of antioxidant activity have been marked in blood plasma in patients with the exacerbation of extensive psoriasis. The dependence of some indices of metabolism on the clinical picture and the severity of skin process, age, family history has been revealed. Conclusion. Metabolism disorders in patients with psoriasis are of systemic character. It seems appropriate to carry out a deep study of metabolism indices in patients with psoriasis with the following correction of the revealed disorders

  16. 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...... with strong analgesics. CONCLUSIONS: Over a period of 6years, a significantly higher number of patients are being treated according to guidelines. Survival following discharge increased over the same period....

  17. 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

  18. 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

  19. 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

  20. Self-reported quality of ADL task performance among patients with COPD exacerbations

    DEFF Research Database (Denmark)

    Bendixen, Hans Jørgen; Wæhrens, Eva Ejlersen; Wilcke, Jon Torgny;

    2014-01-01

    OBJECTIVE: Patients suffering from chronic obstructive pulmonary disease (COPD) experience problems in the performance of activities of daily living (ADL) tasks. The objective was to examine the self-reported quality of ADL task performance among COPD patients, and to investigate whether age......, gender, and routine COPD characteristics correlate with the self-reported ADL ability. METHODS: Eighty patients admitted to hospital with COPD exacerbations participated. In a cross-sectional study, the patients' self-reported ADL ability was assessed using the ADL-Interview (ADL-I) instrument. Data...... more than 90% of the participants reported increased effort and/or fatigue when performing the ADL tasks, up to 88% of the participants relied on help from others in the performance of general household chores like cooking and shopping. Self-reported ADL ability did not correlate with age, gender...

  1. 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, ...

  2. 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.

  3. Importance of adequate immunosuppressive therapy for the recovery of patients with "life-threatening" severe exacerbation of chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    Keiichi Fujiwara; Osamu Yokosuka; Hiroshige Kojima; Tatsuo Kanda; Hiromitsu Saisho; Hiroyuki Hirasawa; Hiroshi Suzuki

    2005-01-01

    AIM: Hepatitis B virus (HBV) re-activation often occurs spontaneously or after withdrawal of immunosuppressive therapy in patients with chronic hepatitis B. Severe exacerbation, sometimes developing into fulminant hepatic failure, is at high risk of mortality. The efficacy of corticosteroid therapy in "clinically severe" exacerbation of chronic hepatitis B has not been well demonstrated. In this study we evaluated the efficacy of early introduction of high-dose corticosteroid therapy in patients with lifethreatening severe exacerbation of chronic hepatitis B.METHODS: Twenty-two patients, 14 men and 8 women,were defined as "severe" exacerbation of chronic hepatitis B using uniform criteria and enrolled in this study. Eleven patients were treated with corticosteroids at 60 mg or more daily with or without anti-viral drugs within 10 d after the diagnosis of severe disease ("early high-dose"group) and 11 patients were either treated more than 10 d or untreated with corticosteroids ("non-early high-dose"group).RESULTS: Mean age, male-to-female ratio, mean prothrombin time (PT) activity, alanine transaminase (ALT)level, total bilirubin level, positivity of HBeAg, mean IgMHBc titer, and mean HBV DNA polymerase activity did not differ between the two groups. Ten of 11 patients of the "early high-dose" group survived, while only 2 of 11 patients of the "non-early high-dose" group survived (P<0.001). During the first 2 wk after the introduction of corticosteroids, improvements in PT activities and total bilirubin levels were observed in the "early high-dose"group. Both ALT levels and HBV DNA polymerase levels fell in both groups.CONCLUSION: The introduction of high-dose corticosteroid can reverse deterioration in patients with "clinically lifethreatening" severe exacerbation of chronic hepatitis B,when used in the early stage of illness.

  4. The chronic obstructive pulmonary disease assessment test improves the predictive value of previous exacerbations for poor outcomes in COPD

    Science.gov (United States)

    Miravitlles, Marc; García-Sidro, Patricia; Fernández-Nistal, Alonso; Buendía, María Jesús; Espinosa de los Monteros, María José; Esquinas, Cristina; Molina, Jesús

    2015-01-01

    Introduction Chronic obstructive pulmonary disease (COPD) exacerbations have a negative impact on the quality of life of patients and the evolution of the disease. We have investigated the prognostic value of several health-related quality of life questionnaires to predict the appearance of a composite event (new ambulatory or emergency exacerbation, hospitalization, or death) over a 1-year follow-up. Methods This was a multicenter, prospective, observational study. Patients completed four questionnaires after recovering from an exacerbation (COPD Assessment Test [CAT], a Clinical COPD Questionnaire [CCQ], COPD Severity Score [COPDSS], and Airways Questionnaire [AQ20]). Patients were followed-up until the appearance of the composite event or for 1 year, whichever came first. Results A total of 497 patients were included in the study. The majority of them were men (89.7%), with a mean age of 68.7 (SD 9.2) years, and a forced expiratory volume in 1 second of 47.1% (SD 17.5%). A total of 303 (61%) patients experienced a composite event. Patients with an event had worse mean scores of all questionnaires at baseline compared to patients without event: CAT=12.5 vs 11.3 (P=0.028); CCQ=2.2 vs 1.9 (P=0.013); COPDSS=12.3 vs 10.9 (P=0.001); AQ20=8.3 vs 7.5 (P=0.048). In the multivariate analysis, only previous history of exacerbations and CAT score ≥13.5 were significant risk factors for the composite event. A CAT score ≥13.5 increased the predictive value of previous exacerbations with an area under the receiver operating characteristic curve of 0.864 (95% CI: 0.829–0.899; P=0.001). Conclusion The predictive value of previous exacerbations significantly increased only in one of the four trialled questionnaires, namely in the CAT questionnaire. However, previous history of exacerbations was the strongest predictor of the composite event. PMID:26664105

  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. 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.

  8. 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...

  9. 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, ...

  10. 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

  11. 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...

  12. 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.

  13. 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

  14. 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

  15. Impact of roflumilast on exacerbations of COPD, health care utilization, and costs in a predominantly elderly Medicare Advantage population

    Directory of Open Access Journals (Sweden)

    Moll K

    2015-03-01

    Full Text Available Keran Moll,1 Shawn X Sun,2 Jeffrey J Ellis,1 Andrew Howe,1 Alpesh Amin3 1Comprehensive Health Insights, Inc., Humana, Louisville, KY, USA; 2Health Economics and Outcomes Research, Forest Laboratories, LLC, an affiliate of Actavis, Inc., Jersey City, NJ, USA; 3Department of Medicine, University of California-Irvine, Orange, CA, USA Background: Chronic obstructive pulmonary disease (COPD exacerbations are associated with declining lung function and health-related quality of life, and increased hospitalization and mortality. Clinical trials often poorly represent the elderly and thus have only partial applicability to their clinical care. Objective: To compare exacerbations, COPD-related health care utilization (HCU, and costs in a predominantly elderly Medicare COPD population initiated on roflumilast versus those not initiated on roflumilast.Methods: Deidentified administrative claims data from a large, national payer were utilized. Medicare patients aged 40–89 years with at least one COPD diagnosis from May 1, 2010 to December 31, 2012 were included. Members with at least one roflumilast pharmacy claim (index were assigned to the roflumilast group and those without were assigned to the non-roflumilast group. Proxy index dates for the non-roflumilast group were randomly assigned for similar distribution of all patients’ time at risk. Subjects with at least one pre-index COPD exacerbation had to be continuously enrolled for ≥365 days pre-index and post-index. Unadjusted and adjusted difference-in-difference (DID analyses contrasted pre-index with post-index changes in exacerbations, HCU, and costs of roflumilast treatment compared with non-roflumilast treatment.Results: A total of 500 roflumilast and 60,145 non-roflumilast patients were included (mean age 69.7 and 72.3 years, respectively; P<0.0001. Unadjusted DID favored roflumilast for all exacerbations, with greater pre-index to post-index reductions in mean per 30-day COPD

  16. Respiratory tract exacerbations revisited: ventilation, inflammation, perfusion, and structure (VIPS) monitoring to redefine treatment.

    Science.gov (United States)

    Tiddens, Harm A W M; Stick, Stephen M; Wild, Jim M; Ciet, Pierluigi; Parker, Geoffrey J M; Koch, Armin; Vogel-Claussen, Jens

    2015-10-01

    For cystic fibrosis (CF) patients older than 6 years there are convincing data that suggest respiratory tract exacerbations (RTE) play an important role in the progressive loss of functional lung tissue. There is a poor understanding of the pathobiology of RTE and whether specific treatment of RTE reduces lung damage in the long term. In addition, there are limited tools available to measure the various components of CF lung disease and responses to therapy. Therefore, in order to better understand the impact of RTE on CF lung disease we need to develop sensitive measures to characterize RTE and responses to treatment; and improve our understanding of structure-function changes during treatment of RTE. In this paper we review our current knowledge of the impact of RTE on the progression of lung disease and identify strategies to improve our understanding of the pathobiology of RTE. By improving our knowledge regarding RTE in CF we will be better positioned to develop approaches to treatment that are individualized and that can prevent permanent structural damage. We suggest the development of a ventilation, perfusion, inflammation and structure (VIPS)-MRI suite that supplies the clinician with data on ventilation, inflammation, perfusion, and structure in one MRI session. VIPS-MRI could be an important step to better understand the factors that contribute to and limit treatment efficacy of RTE.

  17. Hyperlipidemia exacerbates cerebral injury through oxidative stress, inflammation and neuronal apoptosis in MCAO/reperfusion rats.

    Science.gov (United States)

    Cao, Xiao-Lu; Du, Jing; Zhang, Ying; Yan, Jing-Ting; Hu, Xia-Min

    2015-10-01

    Recent studies showed that hyperglycemia enhanced brain damage when subjected to transient cerebral ischemic stroke. However, the etiologic link between them has been less known. In the present study, based on an experimental rat's model of hyperlipidemia combined with cerebral ischemia-reperfusion injury (I/R), we herein showed that hyperlipidemia induced by high-fat diet (HFD) resulted in considerable increase in serum triglycerides, cholesterol and low-density lipoprotein cholesterol, and remarkable decrease in serum high-density lipoprotein cholesterol, which associated with an exacerbation on neurological deficit, cerebral infarct and terminal deoxynucleotidyl transferase-mediated nick end labeling-positive cells in the ischemic hemisphere of cerebral I/R rats treated with HFD diet. The data showed that serum superoxide dismutase activity and glutathione peroxides content were significantly decreased, while malondialdehyde level was obviously increased by hyperlipidemia or cerebral I/R alone, especially by coexistence of hyperlipidemia and cerebral I/R; meantime, hyperlipidemia also enhanced cerebral I/R-induced protein expression of cytochrome P450 2E1 (CYP2E1) and the levels of pro-inflammatory factors tumor necrosis factor-α and IL-6 in the ischemic hemispheres. Furthermore, the combined action of hyperlipidemia and cerebral I/R resulted in a protein increase expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 compared to hyperlipidemia or cerebral I/R alone. Meanwhile, this study also showed that hyperlipidemia significantly enhanced cerebral I/R-induced transfer of cytochrome c from mitochondria to cytosolic and the protein expressions of Apaf-1 and caspase-3, but also decreased cerebral I/R-induced bcl-2 protein expression. The results reveal that hyperlipidemia exacerbates cerebral I/R-induced injury through the synergistic effect on CYP2E1 induction, which further induces reactive oxygen species formation, oxidative

  18. Radiation damage

    CERN Document Server

    Heijne, Erik H M; CERN. Geneva

    1998-01-01

    a) Radiation damage in organic materials. This series of lectures will give an overview of radiation effects on materials and components frequently used in accelerator engineering and experiments. Basic degradation phenomena will be presented for organic materials with comprehensive damage threshold doses for commonly used rubbers, thermoplastics, thermosets and composite materials. Some indications will be given for glass, scintillators and optical fibres. b) Radiation effects in semiconductor materials and devices. The major part of the time will be devoted to treat radiation effects in semiconductor sensors and the associated electronics, in particular displacement damage, interface and single event phenomena. Evaluation methods and practical aspects will be shown. Strategies will be developed for the survival of the materials under the expected environmental conditions of the LHC machine and detectors. I will describe profound revolution in our understanding of black holes and their relation to quantum me...

  19. Benchmark dose estimation for cadmium-induced renal tubular damage among environmental cadmium-exposed women aged 35-54 years in two counties of China.

    Directory of Open Access Journals (Sweden)

    Jia Hu

    Full Text Available A number of factors, including gender, age, smoking habits, and occupational exposure, affect the levels of urinary cadmium. Few studies have considered these influences when calculating the benchmark dose (BMD of cadmium. In the present study, we aimed to calculate BMDs and their 95% lower confidence bounds (BMDLs for cadmium-induced renal tubular effects in an age-specific population in south-central China.In this study, urinary cadmium, β2-microglobulin, and N-acetyl-β-D-glucosaminidase levels were measured in morning urine samples from 490 randomly selected non-smoking women aged 35-54 years. Participants were selected using stratified cluster sampling in two counties (counties A and B in China. Multiple regression and logistic regression analyses were used to investigate the dose-response relationship between urinary cadmium levels and tubular effects. BMDs/BMDLs corresponding to an additional risk (benchmark response of 5% and 10% were calculated with assumed cut-off values of the 84th and 90th percentile of urinary β2-microglobulin and N-acetyl-β-D-glucosaminidase levels of the controls.Urinary levels of β2-microglobulin and N-acetyl-β-D-glucosaminidase increased significantly with increasing levels of urinary cadmium. Age was not associated with urinary cadmium levels, possibly because of the narrow age range included in this study. Based on urinary β2-microglobulin and N-acetyl-β-D-glucosaminidase, BMDs and BMDLs of urinary cadmium ranged from 2.08 to 3.80 (1.41-2.18 µg/g cr for subjects in county A and from 0.99 to 3.34 (0.74-1.91 µg/g cr for those in county B. The predetermined benchmark response of 0.05 and the 90th percentiles of urinary β2-microglobulin and N-acetyl-β-D-glucosaminidase levels of the subjects not exposed to cadmium (i.e., the control group served as cut-off values.The obtained BMDs of urinary cadmium were similar to the reference point of 1 µg/g cr, as suggested by the European Food Safety Authority

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

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    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

  1. The heart-liver metabolic axis: defective communication exacerbates disease.

    Science.gov (United States)

    Baskin, Kedryn K; Bookout, Angie L; Olson, Eric N

    2014-04-01

    The heart has been recognized as an endocrine organ for over 30 years (de Bold, 2011); however, little is known about how the heart communicates with other organs in the body, and even less is known about this process in the diseased heart. In this issue of EMBO Molecular Medicine, Magida and Leinwand (2014) introduce the concept that a primary genetic defect in the heart results in aberrant hepatic lipid metabolism, which consequently exacerbates hypertrophic cardiomyopathy (HCM). This study provides evidence in support of the hypothesis that crosstalk occurs between the heart and liver, and that this becomes disrupted in the diseased state.

  2. 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: (...

  3. 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.

  4. 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

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

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    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

  6. 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

  7. 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

  8. Catastrophic optical bulk damage (COBD) processes in aged and proton-irradiated high power InGaAs-AlGaAs strained quantum well lasers

    Science.gov (United States)

    Sin, Yongkun; LaLumondiere, Stephen; Foran, Brendan; Lotshaw, William; Moss, Steven C.

    2013-02-01

    Recent remarkable success of fiber lasers and amplifiers results from continued improvements in performance characteristics of broad-area InGaAs-AlGaAs strained quantum well (QW) lasers. Unprecedented characteristics of single emitters include optical output powers of over 20 W and power conversion efficiencies of over 70% under CW operation. Leading high power laser diode manufacturers have recently demonstrated encouraging reliability in these lasers mainly targeted for industrial applications, but long-term reliability of these lasers has never been demonstrated for satellite communication systems in the space environment. Furthermore, as reported by two groups in 2009, the dominant failure mode of these lasers is catastrophic optical bulk damage (COBD), which is a new failure type that requires physics of failure investigation to understand its root causes. For the present study, we investigated reliability, proton radiation effects, and the root causes of COBD processes in MOCVD-grown broad-area InGaAs-AlGaAs strained QW lasers using various failure mode analysis (FMA) techniques. Two different approaches, accelerated life-testing and proton irradiation, were taken to generate lasers at different stages of degradation. Our objectives were to (i) study the effects of point defects introduced during crystal growth and those induced by proton irradiation with different energies and fluences in the lasers on degradation processes and to (ii) compare trap characteristics and carrier dynamics in pre- and post-stressed lasers with those in pre- and post-proton irradiated lasers. During entire accelerated life-tests, time resolved electroluminescence (TREL) techniques were employed to observe formation of a hot spot and subsequent formation and progression of dark spots and dark lines through windowed n-contacts.

  9. 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.

  10. 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.

  11. Sputum Bacterial and Fungal Dynamics during Exacerbations of Severe COPD.

    Directory of Open Access Journals (Sweden)

    Jin Su

    Full Text Available The changes in the microbial community structure during acute exacerbations of severe chronic obstructive pulmonary disease (COPD in hospitalized patients remain largely uncharacterized. Therefore, further studies focused on the temporal dynamics and structure of sputum microbial communities during acute exacerbation of COPD (AECOPD would still be necessary. In our study, the use of molecular microbiological techniques provided insight into both fungal and bacterial diversities in AECOPD patients during hospitalization. In particular, we examined the structure and varieties of lung microbial community in 6 patients with severe AECOPD by amplifying 16S rRNA V4 hyper-variable and internal transcribed spacer (ITS DNA regions using barcoded primers and the Illumina sequencing platform. Sequence analysis showed 261 bacterial genera representing 20 distinct phyla, with an average number of genera per patient of >157, indicating high diversity. Acinetobacter, Prevotella, Neisseria, Rothia, Lactobacillus, Leptotrichia, Streptococcus, Veillonella, and Actinomyces were the most commonly identified genera, and the average total sequencing number per sputum sample was >10000 18S ITS sequences. The fungal population was typically dominated by Candia, Phialosimplex, Aspergillus, Penicillium, Cladosporium and Eutypella. Our findings highlight that COPD patients have personalized structures and varieties in sputum microbial community during hospitalization periods.

  12. 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.

  13. 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)

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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...... with strong analgesics. CONCLUSIONS:  Over a period of 6years, a significantly higher number of patients are being treated according to guidelines. Survival following discharge increased over the same period....

  19. The Effect of Smartphone Interventions on Patients With Chronic Obstructive Pulmonary Disease Exacerbations: A Systematic Review and Meta-Analysis

    Science.gov (United States)

    Alwashmi, Meshari; Davis, Erin; Marra, Carlo; Gamble, John-Michael; Abu Ashour, Waseem

    2016-01-01

    Background The prevalence and mortality rates of chronic obstructive pulmonary disease (COPD) are increasing worldwide. Therefore, COPD remains a major public health problem. There is a growing interest in the use of smartphone technology for health promotion and disease management interventions. However, the effectiveness of smartphones in reducing the number of patients having a COPD exacerbation is poorly understood. Objective To summarize and quantify the association between smartphone interventions and COPD exacerbations through a comprehensive systematic review and meta-analysis. Methods A comprehensive search strategy was conducted across relevant databases (PubMed, Embase, Cochrane, CINHA, PsycINFO, and the Cochrane Library Medline) from inception to October 2015. We included studies that assessed the use of smartphone interventions in the reduction of COPD exacerbations compared with usual care. Full-text studies were excluded if the investigators did not use a smartphone device or did not report on COPD exacerbations. Observational studies, abstracts, and reviews were also excluded. Two reviewers extracted the data and conducted a risk of bias assessment using the US Preventive Services Task Force quality rating criteria. A random effects model was used to meta-analyze the results from included studies. Pooled odds ratios were used to measure the effectiveness of smartphone interventions on COPD exacerbations. Heterogeneity was measured using the I2statistic. Results Of the 245 unique citations screened, 6 studies were included in the qualitative synthesis. Studies were relatively small with less than 100 participants in each study (range 30 to 99) and follow-up ranged from 4-9 months. The mean age was 70.5 years (SD 5.6) and 74% (281/380) were male. The studies varied in terms of country, type of smartphone intervention, frequency of data collection from the participants, and the feedback strategy. Three studies were included in the meta-analysis. The

  20. Throat infections are associated with exacerbation in a substantial proportion of patients with chronic plaque psoriasis

    OpenAIRE

    Thorleifsdottir, Ragna H.; Eysteinsdottir, Jenna H.; Olafsson, Jon H; Sigurdsson, Martin I; Johnston, Andrew; Valdimarsson, Helgi; Sigurgeirsson, Bardur

    2016-01-01

    Streptococcal throat infections are known to trigger or exacerbate psoriasis, and several studies support the benefit of tonsillectomy. To evaluate the potential of tonsillectomy as a treatment, we used a retrospective study-specific questionnaire to assess the proportion of psoriasis patients with sore throat-associated psoriasis exacerbations. Our survey sampled 275 psoriasis patients. 42% of patients with plaque psoriasis reported sore throat-associated psoriasis exacerbations, and 72% of ...

  1. 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...

  2. A case of hypoxic encephalopathy with delayed exacerbation

    Directory of Open Access Journals (Sweden)

    Takeshi Hayashi

    2008-10-01

    Full Text Available Takeshi Hayashi, Kimihiko HattoriDepartment of Neurology, Fuji Heavy Industries Health Insurance Corporation, Ota General Hospital, Ota, Gunma, JapanAbstract: Most patients contract hypoxic encephalopathy after suffering a cardiac arrest. They usually endure severe neurological sequelae and the temporal profile of the disease progression remains unclear. This case study shows how the effects of hypoxic encephalopathy continue to progress for several years after the initial event. Up to eight years after the hypoxic insult, the patient’s intellect steadily deteriorated, and brain atrophy progressed. As the hypoxic insult on the brain is only transient, the neurological disability seems not to be exacerbated for years. However, our case indicates that this disorder may have a long progression.Keywords: dementia, encephalopathy, hypoxia, MRI

  3. 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.

  4. 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

  5. [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

  6. Food allergen-mediated exacerbations of oral lichen planus.

    Science.gov (United States)

    Chen, H X; Yount, W J; Culton, D A

    2016-10-01

    Erosive oral lichen planus (OLP) is a chronic autoimmune condition of unknown aetiology, characterized by periods of exacerbation and quiescence. Many patients with OLP report triggers of flares that overlap with triggers of other oral diseases, including oral allergy syndrome (OAS), an IgE-mediated food allergy. We report a case that, to our knowledge, is the first reported case of concurrent OLP and OAS diagnoses, which provides insight into the triggers of OLP and the role of trigger avoidance. A woman in her 60s presented with erosive OLP refractory to prednisone and azathioprine. She reported that certain food exposures triggered flares of her OLP. She was subsequently diagnosed with concurrent OAS, and avoidance of food allergens resulted in a clinically significant improvement in her OLP, eventually allowing her to taper off systemic treatment altogether. Further studies are needed to pinpoint common triggers and examine the role of trigger avoidance as a management strategy for OLP. PMID:27663157

  7. RIP3-dependent necrosis induced inflammation exacerbates atherosclerosis.

    Science.gov (United States)

    Meng, Lingjun; Jin, Wei; Wang, Yuhui; Huang, Huanwei; Li, Jia; Zhang, Cai

    2016-04-29

    Atherothrombotic vascular disease is already the leading cause of mortality worldwide. Atherosclerosis shares features with diseases caused by chronic inflammation. More attention should concentrates on the innate immunity effect atherosclerosis progress. RIP3 (receptor-interacting protein kinase 3) act through the transcription factor named Nr4a3 (Nuclear orphan receptors) to regulate cytokine production. Deletion RIP3 decreases IL-1α production. Injection of anti-IL-1α antibody protects against the progress of atherosclerosis in ApoE -/- mice. RIP3 as a molecular switch in necrosis, controls macrophage necrotic death caused inflammation. Inhibiting necrosis will certainly reduce atherosclerosis through limit inflammation. Necrotic cell death caused systemic inflammation exacerbated cardiovascular disease. Inhibition of necrosis may yield novel therapeutic targets for treatment in years to come.

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

    DEFF Research Database (Denmark)

    Ruzsics, Istvan; Nagy, Lajos; Keki, Sandor;

    2016-01-01

    (ADMA, SDMA) is related to hypoxia. In COPD, a rise in ADMA results in a shift of L-arginine breakdown, contributing to airway obstruction. We aimed to compare serum levels of ADMA, SDMA and L-arginine in patients with and without AECOPD. METHODS: L-arginine metabolites quantified by high......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......-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....

  9. 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

  10. 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.

  11. 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)

  12. 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.

  13. 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.

  14. 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

  15. 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

  16. 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.

  17. Exacerbation of alcohol-induced oxidative stress in rats by polyunsaturated fatty acids and iron load

    Directory of Open Access Journals (Sweden)

    S N Patere

    2011-01-01

    Full Text Available The hypothesis that excessive intake of vegetable oil containing polyunsaturated fatty acids and iron load precipitate alcohol-induced liver damage was investigated in a rat model. In order to elucidate the mechanism underlying this synergism, the serum levels of iron, total protein, serum glutamate pyruvate transaminase, liver thiobarbituric acid reactive substances, and activities of antioxidant enzymes superoxide dismutase, catalase in liver of rats treated with alcohol, polyunsaturated fatty acids and iron per se and in combination were examined. Alcohol was fed to the rats at a level of 10-30% (blood alcohol was maintained between 150-350 mg/dl by using head space gas chromatography, polyunsaturated fatty acids at a level of 15% of diet and carbonyl iron 1.5-2% of diet per se and in combination to different groups for 30 days. Hepatotoxicity was assessed by measuring serum glutamate pyruvate transaminase, which was elevated and serum total protein, which was decreased significantly in rats fed with a combination of alcohol, polyunsaturated fatty acids and iron. It was also associated with increased lipid peroxidation and disruption of antioxidant defense in combination fed rats as compared to rats fed with alcohol or polyunsaturated fatty acids or iron. The present study revealed significant exacerbation of the alcohol-induced oxidative stress in presence of polyunsaturated fatty acids and iron.

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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...

  3. Antibiotics against Pseudomonas aeruginosa for COPD exacerbation in ICU: a 10-year retrospective study

    Directory of Open Access Journals (Sweden)

    Planquette B

    2015-02-01

    Full Text Available Benjamin Planquette,1–4 Julien Péron,2 Etienne Dubuisson,1 Ariane Roujansky,1 Virginie Laurent,1 Alban Le Monnier,3 Stephane Legriel,1 Alexis Ferre,4 Fabrice Bruneel,1 Peter G Chiles,5 Jean P Bedos1 1Réanimation Polyvalente, Centre Hospitalier de Versailles, Le Chesnay, France; 2Unité de Biostatistique Médicale, Hôpital Lyon Sud, Lyon, France; 3Service de Microbiologie, Centre Hospitalier de Versailles, Le Chesnay, France; 4Service de Pneumologie et de Soins Intensifs, Hôpital Européen Georges Pompidou, Université Paris René Descartes, Paris, France; 5Division of Pulmonary and Critical Care Medicine, University of California, San Diego, La Jolla, CA, USA Summary: Chronic obstructive pulmonary disease (COPD is a frequent source of hospitalization. Antibiotics are largely prescribed during COPD exacerbation. Our hypothesis is that large broad-spectrum antibiotics are more and more frequently prescribed. Our results confirm this trend and highlight that the increase in large broad-spectrum use in COPD exacerbation is largely unexplained. Background: Acute COPD exacerbation (AECOPD is frequently due to respiratory tract infection, and the benefit of antipseudomonal antibiotics (APA is still debated. Health care–associated pneumonia (HCAP was defined in 2005 and requires broad-spectrum antibiotherapy. The main objectives are to describe the antibiotic use for AECOPD in intensive care unit and to identify factors associated with APA use and AECOPD prognosis. Methods: We conducted a monocentric, retrospective study on all AECOPDs in the intensive care unit treated by antibiotics for respiratory tract infection. Treatment failure (TF was defined by death, secondary need for mechanical ventilation, or secondary systemic steroid treatment. A multivariate analysis was used to assess factors associated with APA prescription and TF. Results: From January 2000 to December 2011, 111 patients were included. Mean age was 69 years (±12, mean

  4. Pulmonary Function Tests in Emergency Department Pediatric Patients with Acute Wheezing/Asthma Exacerbation

    Directory of Open Access Journals (Sweden)

    Kathryn Giordano

    2012-01-01

    Full Text Available Background. Pulmonary function tests (PFT have been developed to analyze tidal breathing in patients who are minimally cooperative due to age and respiratory status. This study used tidal breathing tests in the ED to measure asthma severity. Design/Method. A prospective pilot study in pediatric patients (3 to 18 yrs with asthma/wheezing was conducted in an ED setting using respiratory inductance plethysmography and pneumotachography. The main outcome measures were testing feasibility, compliance, and predictive value for admission versus discharge. Results. Forty patients were studied, of which, 14 (35% were admitted. Fifty-five percent of the patients were classified as a mild-intermittent asthmatic, 30% were mild-persistent asthmatics, 12.5% were moderate-persistent asthmatics, and 2.5% were severe-persistent. Heart rate was higher in admitted patients as was labored breathing index, phase angle, and asthma score. Conclusions. Tidal breathing tests provide feasible, objective assessment of patient status in the enrolled age group and may assist in the evaluation of acute asthma exacerbation in the ED. Our results demonstrate that PFT measurements, in addition to asthma scores, may be useful in indicating the severity of wheezing/asthma and the need for admission.

  5. 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

  6. 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...

  7. 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.

  8. 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.

  9. Psychological Factors and Pain Exacerbation in Knee Osteoarthritis : A Web Based Case-Crossover Study

    NARCIS (Netherlands)

    Erfani, Tahereh; Keefe, Francis; Bennell, Kim; Chen, J; Makovey, J; Metcalf, B; Williams, A.D.; Zhang, Y; Hunter, David

    2015-01-01

    OBJECTIVES: The pain experienced by osteoarthritis (OA) patients is neither constant nor unchanging and patients experience episodes of pain exacerbations. Using an innovative web based case-crossover design, we evaluated whether psychological factors are risk factors for pain exacerbations in patie

  10. 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...

  11. 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...

  12. 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...

  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. The inflammasome pathway in stable COPD and acute exacerbations

    Directory of Open Access Journals (Sweden)

    Rosa Faner

    2016-07-01

    Full Text Available Chronic obstructive pulmonary disease (COPD is characterised by pulmonary and systemic inflammation that bursts during exacerbations of the disease (ECOPD. The NLRP3 inflammasome is a key regulatory molecule of the inflammatory response. Its role in COPD is unclear. We investigated the NLRP3 inflammasome status in: 1 lung tissue samples from 38 patients with stable COPD, 15 smokers with normal spirometry and 14 never-smokers; and 2 sputum and plasma samples from 56 ECOPD patients, of whom 41 could be reassessed at clinical recovery. We observed that: 1 in lung tissue samples of stable COPD patients, NLRP3 and interleukin (IL-1β mRNA were upregulated, but both caspase-1 and ASC were mostly in inactive form, and 2 during infectious ECOPD, caspase-1, oligomeric ASC and associated cytokines (IL-1β, IL-18 were significantly increased in sputum compared with clinical recovery. The NLRP3 inflammasome is primed, but not activated, in the lungs of clinically stable COPD patients. Inflammasome activation occurs during infectious ECOPD. The results of this study suggest that the inflammasome participates in the inflammatory burst of infectious ECOPD.

  15. 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

  16. 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.

  17. 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.

  18. Effects of Dynamic Pulse Pressure on Renal Damage in Aged Patients with Primary Hypertension%老年高血压患者脉压差对肾脏损害的影响研究

    Institute of Scientific and Technical Information of China (English)

    吴红红; 段磊; 山努佳; 何英

    2011-01-01

    目的 探讨动态脉压对老年高血压患者肾脏损害的影响.方法 选择原发性高血压患者165例,按24 h平均脉压(MPP)分为两组:24 h MPP≥60 mm Hg为A组,24 h MPP<60 mm Hg为B组;另选健康体检正常者为对照组,均进行血清肌酐、动态血压测定.结果 3组24 h平均收缩压(MSBP)、24 h平均舒张压(MDBP)、24 h MPP、血清肌酐、尿清蛋白排泄率(UAER)、肾小球滤过率(GRF)水平比较,差异均有统计学意义(P<0.05).其中A组和B组患者24 h MSBP、24 h MPP较C组明显升高(P<0.05);与B组比较,A组患者上述指标明显升高(P<0.05);A组血清肌酐明显高于B组和C组,24 h MDBP及GRF低于B组和C组(P<0.05).结论 动态脉压增大与老年高血压患者靶器官结构和功能的损害相关;动态脉压越大,靶器官损害越严重.%Objective To investigate the effects of dynamic pulse pressure on renal damage in aged patients with primary hypertension.Methods A total of 165 aged patients with primary hypertension were divided into two groups ( group A: 24 h MPP ≥60 mm Hg; group B∶ 24 h MPP < 60 mm Hg ) according to the 24 hour mean pulse pressure ( 24 h MPP ).Healthy subjects were enrolled as the control group ( group C ).Serum creatinine levels and data from ambulatory blood pressure monitoring were collected from all subjects.Results Comparesion of 24 h mean systolic pressure ( MSBP), 24 h mean diastolic blood pressure ( MDBP ), 24 h MPP, serum creatinine, urinary albumin excretion rate ( UAER ), glomerular filtration rate ( GRF ) among the three groups showed significant differences ( P <0.05 ).The 24 h MSBP and 24 h MPP levels were found to be significantly higher in group A and group B compared with group C ( P < 0.01 ), with group A higher than group B ( P < 0.01 ).Group A also had elevated serum creatinine levels and lower levels of MDBP when compared to group B and group C ( P <0.05 ).Conclusion The elevated dynamic pulse pressure levels are correlated

  19. Damaging effects of hyperglycemia on cardiovascular function: spotlight on glucose metabolic pathways.

    Science.gov (United States)

    Mapanga, Rudo F; Essop, M Faadiel

    2016-01-15

    The incidence of cardiovascular complications associated with hyperglycemia is a growing global health problem. This review discusses the link between hyperglycemia and cardiovascular diseases onset, focusing on the role of recently emerging downstream mediators, namely, oxidative stress and glucose metabolic pathway perturbations. The role of hyperglycemia-mediated activation of nonoxidative glucose pathways (NOGPs) [i.e., the polyol pathway, hexosamine biosynthetic pathway, advanced glycation end products (AGEs), and protein kinase C] in this process is extensively reviewed. The proposal is made that there is a unique interplay between NOGPs and a downstream convergence of detrimental effects that especially affect cardiac endothelial cells, thereby contributing to contractile dysfunction. In this process the AGE pathway emerges as a crucial mediator of hyperglycemia-mediated detrimental effects. In addition, a vicious metabolic cycle is established whereby hyperglycemia-induced NOGPs further fuel their own activation by generating even more oxidative stress, thereby exacerbating damaging effects on cardiac function. Thus NOGP inhibition, and particularly that of the AGE pathway, emerges as a novel therapeutic intervention for the treatment of cardiovascular complications such as acute myocardial infarction in the presence hyperglycemia.

  20. 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

  1. 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 ...

  2. Factors leading to poor outcome of noninvasive positive pressure ventilation in acute exacerbation of chronic obstructive pulmonary disease

    Institute of Scientific and Technical Information of China (English)

    Ashok Kumar; Anoop Kumar; Kelash Rai; Shaista Ghazal; Nadeem Rizvi; Sunil Kumar; Sadhna Notani

    2015-01-01

    Objective:To determine frequency of factors leading to poor outcome of non-invasive positive pressure ventilation in acute exacerbation of chronic obstructive pulmonary disease. Methods:This cross sectional study was conducted at our center between May 2012 and November 2012. A total of 195 diagnosed patients of acute exacerbation of chronic obstructive pulmonary disease meeting the inclusion criteria were selected from the ER department. At the time of admission age was inquired BP, respiratory rate and oxygen saturation will be noted and pedal edema was assessed and investigations were sent for pH assessment. Noninvasive positive pressure ventilation (NIPPV) using BiPAP was applied in spontaneous mode by the help of oronasal mask. Presence of respiratory rate (less than 12/min), systolic blood pressure140 bpm was taken as poor outcome. Results:The average age of the cases was 61.9±9.3 years with male to female ratio being 1.5:1. NIPPV was successful in 151 (77.4%) cases and 44 (22.6%) cases were underwent endotracheal intubation. About 38 (44.7%) of patients with oxygen saturation (82%-86%) had poor prognosis. A total of 40 (55.6%) of patients with pH range 7.20-7.26, required endotracheal intubation, 43 (66.2%) with pedal edema underwent endotracheal intubation. While 29 (24.16%) patients of age>60 years needed endotracheal intubation. Conclusions:In this study, NIPPV was successful in 77.4%cases and 22.6%cases were underwent endotracheal intubation. Pedal edema was the most common factor leading to poor outcomes while age>60 years was the least common factor, 66.2%and 24.2%respectively.

  3. Unilateral Hydronephrosis and Renal Damage after Acute Leukemia

    Directory of Open Access Journals (Sweden)

    Egle Simanauskiene

    2012-01-01

    Full Text Available A 14-year-old boy presented with asymptomatic right hydronephrosis detected on routine yearly ultrasound examination. Previously, he had at least two normal renal ultrasonograms, 4 years after remission of acute myeloblastic leukemia, treated by AML-BFM-93 protocol. A function of the right kidney and no damage on the left was confirmed by a DMSA scan. Right retroperitoneoscopic nephrectomy revealed 3 renal arteries with the lower pole artery lying on the pelviureteric junction. Histologically chronic tubulointerstitial nephritis was detected. In the pathogenesis of this severe unilateral renal damage, we suspect the exacerbation of deleterious effects of cytostatic therapy on kidneys with intermittent hydronephrosis.

  4. Newer antibacterial agents and their potential role in cystic fibrosis pulmonary exacerbation management.

    Science.gov (United States)

    Parkins, M D; Elborn, J S

    2010-09-01

    Pulmonary exacerbations in cystic fibrosis (CF) are frequent events and account for a substantial proportion of the burden of morbidity and mortality in this disease. Antibacterial therapies to treat pulmonary exacerbations are instituted empirically and are individualized based on both patient factors (severity of exacerbation, frequency of exacerbation, recent courses of anti-infectives) and pathogen factors (previously isolated pathogens and in vitro predicted susceptibilities). However, the epidemiology of pathogens infecting CF airways is changing, with increased incidence of methicillin-resistant Staphylococcus aureus (MRSA), drug-resistant Pseudomonas aeruginosa and other Gram-negative non-fermenters such as Stenotrophomonas maltophilia and Achromobacter xylosoxidans. Accordingly, a great need for new and novel agents for the management of acute exacerbations in CF exists. While several antibiotics have recently been approved or are close to approval for clinical use, frequently their emphasis has been for Gram-positive, and specifically MRSA-related, disease. Despite this, these agents may have a role in CF-related exacerbations. This article reviews the spectrum of activity, pharmacokinetics and clinical and theoretical evidence for the use of newer agents including tigecycline, doripenem and ceftobiprole in the management of CF pulmonary exacerbations. Appropriate use of these agents in CF will require detailed CF-specific pharmacokinetic and pharmacodynamic data.

  5. Exacerbation of acetaminophen hepatotoxicity by the anthelmentic drug fenbendazole.

    Science.gov (United States)

    Gardner, Carol R; Mishin, Vladimir; Laskin, Jeffrey D; Laskin, Debra L

    2012-02-01

    Fenbendazole is a broad-spectrum anthelmintic drug widely used to prevent or treat nematode infections in laboratory rodent colonies. Potential interactions between fenbendazole and hepatotoxicants such as acetaminophen are unknown, and this was investigated in this study. Mice were fed a control diet or a diet containing fenbendazole (8-12 mg/kg/day) for 7 days prior to treatment with acetaminophen (300 mg/kg) or phosphate buffered saline. In mice fed a control diet, acetaminophen administration resulted in centrilobular hepatic necrosis and increases in serum transaminases, which were evident within 12 h. Acetaminophen-induced hepatotoxicity was markedly increased in mice fed the fenbendazole-containing diet, as measured histologically and by significant increases in serum transaminase levels. Moreover, in mice fed the fenbendazole-containing diet, but not the control diet, 63% mortality was observed within 24 h of acetaminophen administration. Fenbendazole by itself had no effect on liver histology or serum transaminases. To determine if exaggerated hepatotoxicity was due to alterations in acetaminophen metabolism, we analyzed sera for the presence of free acetaminophen and acetaminophen-glucuronide. We found that there were no differences in acetaminophen turnover. We also measured cytochrome P450 (cyp) 2e1, cyp3a, and cyp1a2 activity. Whereas fenbendazole had no effect on the activity of cyp2e1 or cyp3a, cyp1a2 was suppressed. A prolonged suppression of hepatic glutathione (GSH) was also observed in acetaminophen-treated mice fed the fenbendazole-containing diet when compared with the control diet. These data demonstrate that fenbendazole exacerbates the hepatotoxicity of acetaminophen, an effect that is related to persistent GSH depletion. These findings are novel and suggest a potential drug-drug interaction that should be considered in experimental protocols evaluating mechanisms of hepatotoxicity in rodent colonies treated with fenbendazole.

  6. Viral epidemiology of acute exacerbations of chronic obstructive pulmonary disease.

    Science.gov (United States)

    Dimopoulos, G; Lerikou, M; Tsiodras, S; Chranioti, Aik; Perros, E; Anagnostopoulou, U; Armaganidis, A; Karakitsos, P

    2012-02-01

    The role of viruses in Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) needs further elucidation. The aim of the present study was to evaluate the molecular epidemiology of viral pathogens in AECOPD. Patients presenting to the Emergency Room with AECOPD needing hospitalization were recruited. Oropharyngeal and sputum samples were collected in order to perform microarrays-based viral testing for the detection of respiratory viruses. A total of 200 (100%) patients were analyzed and from them in 107 (53.5%) a virus was detected. The commonest identified viruses were the human Respiratory Syncytial Virus (subtypes A and B) (40.5%), influenza virus (subtypes A, B, C) (11%), rhinovirus (8%) and human Parainfluenza Virus (subtypes A and B) (7.5%). A bacterial pathogen was isolated in 27 (14%) patients and a dual infection due to a bacterial and a viral pathogen was recognised in 14/107 patients. Patients with AECOPD and a viral infection had a lengthier hospital stay (9.2 ± 4.6 vs 7.6 ± 4.3, p < 0.01) while the severity of the disease was no related with significant differences among the groups of the study population. In conclusion, the isolation of a virus was strongly associated with AECOPD in the examined population. The stage of COPD appeared to have no relation with the frequency of the isolated viruses while dual infection with a viral and a bacterial pathogen was not rare. PMID:21983132

  7. 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.

  8. 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.

  9. Obesity Interacts with Cerebral Hypoperfusion to Exacerbate Cognitive Impairment in Older Adults with Heart Failure

    Directory of Open Access Journals (Sweden)

    Michael L. Alosco

    2012-10-01

    Full Text Available Background: Cerebral hypoperfusion accompanies heart failure (HF and is associated with reduced cognitive performance. Obesity is prevalent in persons with HF and is also a likely contributor to cognitive function, as it has been independently linked to cognitive impairment in healthy individuals. The current study examined the association between obesity and cognitive performance among older adults with HF and whether obesity interacts with cerebral hypoperfusion to exacerbate cognitive impairment. Methods: Patients with HF (n = 99, 67.46 ± 11.36 years of age completed neuropsychological testing and impedance cardiography. Cerebral blood flow velocity (CBF-V measured by transcranial Doppler sonography quantified cerebral perfusion and body mass index (BMI operationalized obesity. Results: A hierarchical regression analysis showed that lower CBF-V was associated with reduced performance on tests of attention/executive function and memory. Elevated BMI was independently associated with reduced attention/executive function and language test performance. Notably, a significant interaction between CBF-V and BMI indicated that a combination of hypoperfusion and high BMI has an especially adverse influence on attention/executive function in HF patients. Conclusions: The current findings suggest that cerebral hypoperfusion and obesity interact to impair cognitive performance in persons with HF. These results may have important clinical implications, as HF patients who are at high risk for cerebral hypoperfusion may benefit from weight reduction.

  10. 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

  11. 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

  12. Ovariectomy exacerbates oxidative stress and cardiopathy induced by adriamycin.

    Science.gov (United States)

    Muñoz-Castañeda, Juan Rafael; Muntané, Jordi; Herencia, Carmen; Muñoz, Maria C; Bujalance, Inmaculada; Montilla, Pedro; Túnez, Issac

    2006-02-01

    Ovarian hormone depletion in ovariectomized experimental animals is a useful model with which to study the physiopathological consequences of menopause in women. It has been suggested that menopause is a risk factor for the induction of several cardiovascular disorders. In the present study we analyzed the effects of ovarian hormone depletion by ovariectomy (OVX) in a model of oxidative stress and cardiopathy induced by adriamycin (AD). To evaluate these effects, we measured parameters related to cardiac damage (creatinine kinase, lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase) and oxidative stress (malondialdehyde, catalase, superoxide dismutase, glutathione peroxidase, reduced glutathione, nitric oxide and carbonyl proteins) in cardiac tissue and erythrocytes. OVX was found to alter all markers of oxidative stress and cell damage in cardiac tissue. Similarly, the OVX-derived loss of ovarian hormones enhanced cardiac damage and oxidative stress induced by AD. Our results suggest that antioxidant status in cardiac tissue and erythrocytes is seriously compromised by OVX during the cardiomyopathy induced by AD in experimental animals. In conclusion, the absence of hormones caused by OVX or menopause may induce or accelerate pre-existing cardiovascular dysfunctions.

  13. 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.

  14. Acute Exacerbation of Idiopathic Pulmonary Fibrosis Following Treatment for Cushing's Syndrome.

    Science.gov (United States)

    Ohara, Nobumasa; Kaneko, Masanori; Sato, Kazuhiro; Usuda, Hiroyuki; Tanaka, Junta; Maekawa, Takashi; Sasano, Hironobu; Katakami, Hideki; Kaneko, Kenzo; Kamoi, Kyuzi

    2016-01-01

    A 64-year-old Japanese man with mild reticular shadows in both lungs developed a lung tumor causing ectopic Cushing's syndrome. He was prescribed an adrenal inhibitor, which controlled his hypercortisolemia. However, he developed acute exacerbation of idiopathic pulmonary fibrosis (IPF) and died within weeks. Previous studies have suggested a dosage reduction of corticosteroids for IPF as a triggering event for acute exacerbation. The present case suggests that IPF coexisting with Cushing's syndrome may have been exacerbated after the correction of hypercortisolemia. Therefore, close monitoring of cortisol levels along with the clinical course of IPF is required in similar cases that require the correction of hypercortisolemia.

  15. 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

  16. 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.

  17. Relevance of serology for Mycoplasma pneumoniae diagnosis compared with PCR and culture in acute exacerbation of bronchial asthma.

    Science.gov (United States)

    El Sayed Zaki, Maysaa; Raafat, Doaa; El Metaal, Amal Abd

    2009-01-01

    We studied Mycoplasma pneumoniae as the etiologic pathogen in acute exacerbations of asthma and the value of polymerase chain reaction (PCR), culture, and serologic tests for its accurate diagnosis. For the study, 59 nonsmoking patients with asthma (37 females, 22 males; age, 15-50 years) underwent clinical, radiologic, and laboratory examinations. Bacteria isolated from sputum were Streptococcus pneumoniae (32 [54%]), Staphylococcus aureus (23 [39%]), and M pneumoniae (5 [15%]). All M pneumoniae were associated with S pneumoniae (8/32 [25%]) and S aureus (1/23 [4%]). No M pneumoniae were isolated as single pathogens. Serologic testing for M pneumoniae revealed that all samples were positive for specific IgG; 40 (68%) had a high titer, and 19 (32%) had a moderate titer. Of 59 samples, 29 (49%) were positive by Serodia Myco II gelatin particle testing (Fujirebio, Tokyo, Japan). PCR was positive in 25 samples, all of which had a high IgG titer; all culture-positive cases were PCR+. M pneumoniae is a common bacterial pathogen associated with acute exacerbations of asthma in people 15 years or older. Prompt laboratory diagnosis of M pneumoniae requires direct detection by PCR and culture. A high serologic titer can be a clue for the presence of M pneumoniae.

  18. 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

  19. Standing posture at work and overweight exacerbate varicose veins: Shimane CoHRE Study.

    Science.gov (United States)

    Kohno, Kunie; Niihara, Hiroyuki; Hamano, Tsuyoshi; Takeda, Miwako; Yamasaki, Masayuki; Mizumoto, Kazuo; Nabika, Toru; Morita, Eishin; Shiwaku, Kuninori

    2014-11-01

    Varicose veins (VV) in legs are commonly observed in the general global population. However, the prevalence of and risk factors for VV in Japan are not clear. This study aimed at clarifying the risk factors for VV in traditional rural areas of Shimane prefecture. Subjects (113 men and 205 women aged ≥45 years) were recruited from health examinations in those areas in 2012. VV were defined as a reflux of blood in the great and/or small saphenous vein and incompetent perforating veins detected by ultrasonography. Risk factors for VV were analyzed using logistic regression models that included various parameters. We also investigated the possible interaction between standing at work and overweight and calculated the synergistic index. VV were found in 20.1% of the subjects (12.4% of men and 24.4% of women). The previously known risk factors of prolonged upright standing posture during work, higher body mass index (BMI), female sex, and age were also significant factors for VV. There was a significant combined effect of overweight (BMI ≥25) and prolonged upright standing posture at work [adjusted odds ratio = 3.42; 95% confidence interval (CI), 1.07-10.89], although the synergistic effect was not significant [synergistic index = 1.3; 95% CI, 0.2-8.7]. The prevalence of VV in the traditional rural area of Shimane prefecture was comparable to that reported previously in European countries. Our results confirm that exposure to both prolonged standing at work and overweight exacerbate VV development. This finding is useful to develop strategies for VV prevention. PMID:25298232

  20. Standing posture at work and overweight exacerbate varicose veins: Shimane CoHRE Study.

    Science.gov (United States)

    Kohno, Kunie; Niihara, Hiroyuki; Hamano, Tsuyoshi; Takeda, Miwako; Yamasaki, Masayuki; Mizumoto, Kazuo; Nabika, Toru; Morita, Eishin; Shiwaku, Kuninori

    2014-11-01

    Varicose veins (VV) in legs are commonly observed in the general global population. However, the prevalence of and risk factors for VV in Japan are not clear. This study aimed at clarifying the risk factors for VV in traditional rural areas of Shimane prefecture. Subjects (113 men and 205 women aged ≥45 years) were recruited from health examinations in those areas in 2012. VV were defined as a reflux of blood in the great and/or small saphenous vein and incompetent perforating veins detected by ultrasonography. Risk factors for VV were analyzed using logistic regression models that included various parameters. We also investigated the possible interaction between standing at work and overweight and calculated the synergistic index. VV were found in 20.1% of the subjects (12.4% of men and 24.4% of women). The previously known risk factors of prolonged upright standing posture during work, higher body mass index (BMI), female sex, and age were also significant factors for VV. There was a significant combined effect of overweight (BMI ≥25) and prolonged upright standing posture at work [adjusted odds ratio = 3.42; 95% confidence interval (CI), 1.07-10.89], although the synergistic effect was not significant [synergistic index = 1.3; 95% CI, 0.2-8.7]. The prevalence of VV in the traditional rural area of Shimane prefecture was comparable to that reported previously in European countries. Our results confirm that exposure to both prolonged standing at work and overweight exacerbate VV development. This finding is useful to develop strategies for VV prevention.

  1. 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...

  2. Effect of long-acting beta2 agonists on exacerbation rates of asthma in children

    DEFF Research Database (Denmark)

    Bisgaard, Hans

    2003-01-01

    The purpose of this analysis was to examine the effect of long-acting beta(2)-adrenoceptor agonists (LABAs) on the asthma exacerbation rate in pediatric patients. Randomized controlled trials (RCT) that included the use of LABAs to treat symptoms of pediatric asthma in children on inhaled...... requiring a change in prescribed medication or not defined but reported as an asthma exacerbation or an asthma-related hospitalization. Analysis of data from the eight studies revealed no apparent protection from an asthma exacerbation among children on a LABA compared to patients on comparator treatment....... The relative risk of an asthma exacerbation for LABA compared to placebo or short-acting beta(2)-adrenoceptor agonist (SABA) ranged from 0.95-1.86. The relative risk of hospitalization for asthma in patients treated with LABAs with regular maintenance with ICS ranged from 3.3-21.6 in the three studies...

  3. 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.

  4. 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

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  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. 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...

  11. 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

  12. 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.

  13. 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

  14. UNC5B receptor deletion exacerbates DSS-induced colitis in mice by increasing epithelial cell apoptosis.

    Science.gov (United States)

    Ranganathan, Punithavathi; Jayakumar, Calpurnia; Li, Dean Y; Ramesh, Ganesan

    2014-07-01

    The netrin-1 administration or overexpression is known to protect colon from acute colitis. However, the receptor that mediates netrin-1 protective activities in the colon during colitis remains unknown. We tested the hypothesis that UNC5B receptor is a critical mediator of protective function of netrin-1 in dextran sodium sulfate (DSS)-induced colitis using mice with partial deletion of UNC5B receptor. DSS colitis was performed in mice with partial genetic UNC5B deficiency (UNC5B(+/-) mice) or wild-type mice to examine the role of endogenous UNC5B. These studies were supported by in vitro models of DSS-induced apoptosis in human colon epithelial cells. WT mice developed colitis in response to DSS feeding as indicated by reduction in bw, reduction in colon length and increase in colon weight. These changes were exacerbated in heterozygous UNC5B knockout mice treated with DSS. Periodic Acid-Schiff stained section shows damages in colon epithelium and mononuclear cell infiltration in WT mice, which was further increased in UNC5B heterozygous knockout mice. This was associated with large increase in inflammatory mediators such as cytokine and chemokine expression and extensive apoptosis of epithelial cells in heterozygous knockout mice as compared to WT mice. Overexpression of UNC5B human colon epithelial cells suppressed DSS-induced apoptosis and caspase-3 activity. Moreover, DSS induced large amount of netrin-1 and shRNA mediated knockdown of netrin-1 induction exacerbated DSS-induced epithelial cell apoptosis. Our results suggest that UNC5B is a critical mediator of cell survival in response to stress in colon.

  15. 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...

  16. Contribution of influenza to acute exacerbations of chronic obstructive pulmonary disease in Kashmir, India, 2010-2012.

    Science.gov (United States)

    Koul, Parvaiz A; Khan, Umar H; Asad, Romana; Yousuf, Rubaya; Broor, Shobha; Lal, Renu B; Dawood, Fatimah S

    2015-01-01

    We estimate the contribution of influenza to hospitalizations for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in Kashmir, India. Prospective surveillance for influenza among patients hospitalized with AECOPD was conducted at a tertiary care hospital. Patients had clinical data collected and nasal/throat swabs tested for influenza viruses. Outcomes among patients with and without influenza were compared with logistic regression adjusting for age and underlying conditions. During October 2010-September 2012, 498 patients hospitalized with AECOPD were enrolled, of whom 40 (8%) had received influenza vaccine. Forty (8%) had influenza; influenza virus detection peaked in winter (January-March). Patients with influenza were more likely to die during hospitalization (adjusted OR 3.4, CI 1.0-11.4) than those without.

  17. 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...

  18. Chromosome 17q21 gene variants are associated with asthma and exacerbations but not atopy in early childhood

    DEFF Research Database (Denmark)

    Bisgaard, Hans; Bønnelykke, Klaus; Sleiman, Patrick M A;

    2009-01-01

    RATIONALE: An asthma predisposition locus on chromosome 17q12-q21 has recently been replicated in different ethnic groups. OBJECTIVES: To characterize the asthma and atopy phenotypes in early childhood that associate with the 17q12-21 locus. METHODS: The single nucleotide polymorphism (SNP), rs...... endpoints were based on diary cards and clinic visits every 6 months and at acute symptoms from birth. Lung function, bronchial responsiveness, and sensitization were tested longitudinally from early infancy. MEASUREMENTS AND MAIN RESULTS: rs7216389 was significantly associated with the development......: Variation at the chromosome 17q12-q21 locus was associated with approximately twofold increased risk of recurrent wheeze, asthma, asthma exacerbations, and bronchial hyperresponsiveness from early infancy to school age but without conferring risk of eczema, rhinitis, or allergic sensitization...

  19. 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.

  20. Genetic suppression of HO-1 exacerbates renal damage: reversed by an increase in the antiapoptotic signaling pathway.

    Science.gov (United States)

    Olszanecki, Rafal; Rezzani, Rita; Omura, Shinji; Stec, David E; Rodella, Luigi; Botros, Fady T; Goodman, Alvin I; Drummond, George; Abraham, Nader G

    2007-01-01

    Apoptosis has been shown to contribute to the development of acute and chronic renal failure. The antiapoptotic action of the heme oxygenase (HO) system may represent an important protective mechanism in kidney pathology. We examined whether the lack of HO-1 would influence apoptosis in clipped kidneys of two-kidney, one-clip (2K1C) rats. Five-day-old Sprague-Dawley rats were injected in the left ventricle with approximately 5 x 10(9) colony-forming units/ml of retrovirus containing rat HO-1 antisense (LSN-RHO-1-AS) or control retrovirus (LXSN). After 3 mo, a 0.25-mm U-shaped silver clip was placed around the left renal artery. Animals were killed 3 wk later. Clipping the renal artery in LSN-RHO-1-AS rats did not result in increased HO-1 expression. In contrast to LXSN animals, 2K1C LSN-RHO-1-AS rats showed increased expression of cyclooxygenase 2 (COX-2) and higher 3-nitrotyrosine (3-NT) content as well as increased expression of the proapoptotic protein Apaf-1 and caspase-3 activity. Clipping the renal artery in LXSN rats resulted in increased expression of the antiapoptotic proteins Bcl-2 and Bcl-xl, while clipping the renal artery in LSN-RHO-1-AS rats did not change Bcl-2 levels and decreased the levels of Bcl-xl. Treatment of LSN-RHO-1-AS rats with cobalt protoporphyrin resulted in induction of renal HO-1, which was accompanied by decreases in blood pressure, COX-2, 3-NT, and caspase-3 activity, and increased expression of anti-apoptotic molecules (Bcl-2, Bcl-xl, Akt and p-Akt) in the clipped kidneys. These findings underscore the prominent role of HO-1 in counteracting apoptosis in this 2K1C renovascular hypertension model. PMID:16940561

  1. 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.

  2. 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

    OpenAIRE

    Keeney Paula M; Dunham Lisa D; Morton Stephanie L; Arthur Charles R; Bennett James P

    2009-01-01

    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...

  3. Material Induced Anisotropic Damage

    NARCIS (Netherlands)

    Niazi, M.S.; Wisselink, H.H.; Meinders, V.T.; Boogaard, van den A.H.; Hora, P.

    2012-01-01

    The anisotropy in damage can be driven by two different phenomena; anisotropic defor-mation state named Load Induced Anisotropic Damage (LIAD) and anisotropic (shape and/or distribution) second phase particles named Material Induced Anisotropic Damage (MIAD). Most anisotropic damage models are based

  4. 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)

  5. Economic analysis in admitted patients with acute exacerbation of chronic obstructive pulmonary disease

    Institute of Scientific and Technical Information of China (English)

    CHEN Ya-hong; YAO Wan-zhen; CAI Bai-qiang; WANG Hong; DENG Xiao-mei; GAO Hui-li; HUANG Jia-sheng; WANG Xin-mao

    2008-01-01

    Background The socio-economic burden of acute exacerbation of chronic obstructive pulmonary disease(AECoPD)in Beijing is not fully understood.The study investigated the hospitalization cost in patients with AECOPD and the associated factors.Methods A multi-center,retrospective study was conducted jn the four hospitals in Beijing including two level Ⅲ hospitals and two level Ⅱ hospitals.Patients with AECOPD admixed to the hospitals between January and December in 2006 were enrolled.The hosDitalization cost and its relationship with disease severity and treatment were analyzed.Results Totally 439 patients were enrolled with 294 men(67.0%)and a mean age 73.4 years.The mean hospital stay was 20.7 days.A total of 204 patients(46.5%)had respiratory failure,153(34.9%)with cor pulmonale,123(28.0%)with coronary artery disease,231(52.6%) with hypertension,70(15.9%)with cerebrovascuIar disease and 32(7.3%)with renal failure.The percentage of drug cost to total cost was the highest(71.2%),followed by laboratory cost(16.7%),therapy cost(9.7%),oxygen cost(7.3%),radiology cost(4.5%),examination cost(4.5%),bed cost(4.1%).Correlation analysis showed that cost was positively correlated with age,hospitalization days,co-morbidities such as respiratory failure and cor pulmonale,hypertension.Three hundred and twenty-one patients were further analyzed.The hospitalization cost increased in patients with non-invasive ventilation(P<0.01),invasive mechanical ventilation(P<0.01),ICU stay(P<0.01),antibiotics(P<0.05),systemic steroids(P<0.01),and poor prognosis(P<0.05).Correlation analysis showed that the hospitalization cost was negatively correlated with percentage forced expiratory volume in 1 second (FEV1%)(r=0.149,P<0.05),Ph(r=-0.258,P<0.01),and PaO2(r=-0.131,P<0.05),positively correlated with PaCO2 (r=0.319,P<0.01),non-invasive positive pressure ventilation(r=0.375,P<0.01)and duration(r=0.463,P<0.01),invasive mechanical ventilation(r=0.416,P<0.01)and duration

  6. 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

  7. 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

  8. 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.

  9. 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...

  10. 辐射损伤导致造血干/祖细胞衰老的机理研究%Mechanism of hematopoietic stem/progenitor cell aging induced by radiation damage

    Institute of Scientific and Technical Information of China (English)

    张琛; 孙可; 耿珊; 刘典锋; 张先平; 刘俊; 徐春燕; 王建伟; 王亚平

    2013-01-01

    Objective To explore the mechanism underlying the aging of hematopoietic stem/progenitor cells (HSC/ HPC) induced by radiation stress. Methods Male C57BL/6J mice were divided randomly into radiation group and control group. The radiation group were treated with total 6.5 Gy X-ray radiation for 24 h; the control group received the same treatment except radiation. Thereafter, Sca-1+ HSC/HPC were isolated by magnetic-activated cell sorting (MACS) from bone marrow of all the mice. The distributions of cell cycle were tested by flow cytometry. The percentage of aging cells was detected by SA-β-Gal staining. The potentials of self-renewal and multi-differentiation were measured by CFU-Mix assay. DNA damages of Sca-1+ HSC/HPC were analyzed by single cell gel electrophoresis technique (SCGE). The expressions of senescence-associated genes pl6INK4a, pl9Arf, p53, p2Cip1/Waf1 mRNA were detected by RT-PCR. Western blotting was performed to analyze the expressions of p16INK4a and p21Cip1/Waf1 proteins. Results The purity of Sca-1+ HSC/HPC reached 94% after MACS. Compared with control group cells, after radiation, the number of Sca-1+ HSC/HPC per femur and CFU-Mix sharply decreased (P<0.05), Sca-1+ HSC/HPC apparently showed G1 arrest and elevated percentage of SA-β-Gal positive cells (P<0.05), cell trailing had a prolonged time, and the expressions of senescence-associated genes (p16INK4a, p19Art, p53, p21Cip1/Waf1) and relevant proteins (p16INK4a, p21Cip1/Waf1) were up-regulated significantly (P<0.05). Conclusion DNA damage and senescence-associated biological changes of Sca-1+ HSC/HPC can be achieved by X-ray radiation, which may be involved in p16INK4a-Rb and p19Arf-p53-p21Cip1/Waf1 signal pathways.%目的 探讨辐射损伤导致骨髓造血干/祖细胞(HSC/HPC)衰老的可能机制.方法 雄性C57BL/6J小鼠随机分为辐照组和假辐照组,辐照组小鼠经6.5 Gy的X射线全身一次性辐照,假辐照组小鼠处理同辐照组,但不辐照.辐照后24 h免疫

  11. Twisted gastrulation, a BMP antagonist, exacerbates podocyte injury.

    Directory of Open Access Journals (Sweden)

    Sachiko Yamada

    Full Text Available Podocyte injury is the first step in the progression of glomerulosclerosis. Previous studies have demonstrated the beneficial effect of bone morphogenetic protein 7 (Bmp7 in podocyte injury and the existence of native Bmp signaling in podocytes. Local activity of Bmp7 is controlled by cell-type specific Bmp antagonists, which inhibit the binding of Bmp7 to its receptors. Here we show that the product of Twisted gastrulation (Twsg1, a Bmp antagonist, is the central negative regulator of Bmp function in podocytes and that Twsg1 null mice are resistant to podocyte injury. Twsg1 was the most abundant Bmp antagonist in murine cultured podocytes. The administration of Bmp induced podocyte differentiation through Smad signaling, whereas the simultaneous administration of Twsg1 antagonized the effect. The administration of Bmp also inhibited podocyte proliferation, whereas simultaneous administration of Twsg1 antagonized the effect. Twsg1 was expressed in the glomerular parietal cells (PECs and distal nephron of the healthy kidney, and additionally in damaged glomerular cells in a murine model of podocyte injury. Twsg1 null mice exhibited milder hypoalbuminemia and hyperlipidemia, and milder histological changes while maintaining the expression of podocyte markers during podocyte injury model. Taken together, our results show that Twsg1 plays a critical role in the modulation of protective action of Bmp7 on podocytes, and that inhibition of Twsg1 is a promising means of development of novel treatment for podocyte injury.

  12. 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.

  13. 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

  14. 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.

  15. Gastro-esophageal reflux disease and exacerbations in chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Ingebrigtsen, Truls S; Marott, Jacob L; Vestbo, Jørgen;

    2015-01-01

    BACKGROUND AND OBJECTIVE: We tested the hypothesis that gastro-esophageal reflux disease is a risk factor for exacerbations in individuals with chronic obstructive pulmonary disease (COPD). METHODS: Among 9622 participants in the Copenhagen City Heart Study, we identified 1259 individuals with COPD...... and information on gastro-esophageal reflux disease and the regular use of acid inhibitory treatment. These individuals were followed for 5 years with regard to medically treated COPD exacerbations, which we defined as a short course treatment with oral corticosteroids alone or in combination with antibiotics. We...... applied a multivariable Cox regression analysis with adjustment for well-established risk factors associated with COPD exacerbations or gastro-esophageal reflux disease, including COPD severity, and symptoms. RESULTS: Individuals with COPD and gastro-esophageal reflux disease had more chronic bronchitis...

  16. 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.

  17. 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...

  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. 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)

  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. 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

  2. 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 ...

  3. 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.

  4. 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

  5. Prognostic factors for clinical failure of exacerbations in elderly outpatients with moderate-to-severe COPD

    Directory of Open Access Journals (Sweden)

    Wilson R

    2015-06-01

    Full Text Available Robert Wilson,1 Antonio Anzueto,2 Marc Miravitlles,3 Pierre Arvis,4 Daniel Haverstock,5 Mila Trajanovic,6 Sanjay Sethi7 1Host Defence Unit, Royal Brompton Hospital, London, UK; 2University of Texas Health Science Center, South Texas Veterans Health Care System, San Antonio, TX, USA; 3Pneumology Department, Hospital Universitari Vall d’Hebron, CIBER de Enfermedades Respiratorias (CIBERES, Barcelona, Spain; 4Bayer HealthCare Pharmaceuticals, Loos, France; 5Bayer HealthCare Pharmaceuticals, Whippany, NJ, USA; 6Bayer HealthCare Pharmaceuticals, Toronto, ON, Canada; 7University at Buffalo, Buffalo, NY, USA Background: Acute exacerbations represent a significant burden for patients with moderate-to-severe chronic obstructive pulmonary disease. Each exacerbation episode is frequently associated with a lengthy recovery and impaired quality of life. Prognostic factors for outpatients that may predict poor outcome after treatment with antibiotics recommended in the guidelines, are not fully understood. We aimed to identify pretherapy factors predictive of clinical failure in elderly (≥60 years old outpatients with acute Anthonisen type 1 exacerbations.Trial registration: NCT00656747.Methods: Based on the moxifloxacin in AECOPDs (acute exacerbations of chronic obstructive pulmonary disease trial (MAESTRAL database, this study evaluated pretherapy demographic, clinical, sputum bacteriological factors using multivariate logistic regression analysis, with internal validation by bootstrap replicates, to investigate their possible association with clinical failure at end of therapy (EOT and 8 weeks posttherapy.Results: The analyses found that the independent factors predicting clinical failure at EOT were more frequent exacerbations, increased respiratory rate and lower body temperature at exacerbation, treatment with long-acting anticholinergic drugs, and in vitro bacterial resistance to study drug. The independent factors predicting poor outcome at 8

  6. 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...

  7. Case-fatality of COPD exacerbations: a meta-analysis and statistical modeling approach

    DEFF Research Database (Denmark)

    Hoogendoorn, M; Hoogenveen, R T; Rutten-van Mölken, M P;

    2010-01-01

    and was calculated as 1 minus the (backwardly) extrapolated survival during the stable period at the time of exacerbation onset. The 95% confidence intervals of the estimated case-fatalities were obtained by bootstrapping. A random effect model was used to combine all estimates into a weighted average with 95......%-confidence interval. The meta-analysis based on six studies that fulfilled the inclusion criteria resulted in a weighted average case-fatality rate of 15.6% (95%CI:10.9%-20.3%), ranging from 11.4% to 19.0% for the individual studies. A severe COPD exacerbation requiring hospitalization not only results...

  8. The role of invasive ventilation in exacerbations of chronic obstructive pulmonary disease causing respiratory failure.

    Science.gov (United States)

    Kosky, Christopher; Turton, Charles

    2006-01-01

    Acute hypercapnic respiratory failure in chronic obstructive pulmonary disease can usually be managed initially with medical treatment and non- invasive ventilation. In circumstances where non- invasive ventilation cannot be used or has failed, intubation and invasive ventilation may be lifesaving. The outcome of patients with an exacerbation of COPD requiring invasive ventilation is better than often thought, with a hospital survival of 70-89%. Decisions regarding invasive ventilation made by physicians and patients with COPD are unpredictable and vary with the individual. This article reviews the role of invasive ventilation in exacerbations of COPD to assist decision making.

  9. Drugs That May Cause or Exacerbate Heart Failure: A Scientific Statement From the American Heart Association.

    Science.gov (United States)

    Page, Robert L; O'Bryant, Cindy L; Cheng, Davy; Dow, Tristan J; Ky, Bonnie; Stein, C Michael; Spencer, Anne P; Trupp, Robin J; Lindenfeld, JoAnn

    2016-08-01

    Heart failure is a common, costly, and debilitating syndrome that is associated with a highly complex drug regimen, a large number of comorbidities, and a large and often disparate number of healthcare providers. All of these factors conspire to increase the risk of heart failure exacerbation by direct myocardial toxicity, drug-drug interactions, or both. This scientific statement is designed to serve as a comprehensive and accessible source of drugs that may cause or exacerbate heart failure to assist healthcare providers in improving the quality of care for these patients.

  10. 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.

  11. 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)

  12. 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

  13. Gestational age

    Science.gov (United States)

    Fetal age - gestational age; Gestation; Neonatal gestational age; Newborn gestational age ... Gestational age can be determined before or after birth. Before birth, your health care provider will use ...

  14. 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.

  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. Mechanical Forces Exacerbate Periodontal Defects in Bsp-null Mice.

    Science.gov (United States)

    Soenjaya, Y; Foster, B L; Nociti, F H; Ao, M; Holdsworth, D W; Hunter, G K; Somerman, M J; Goldberg, H A

    2015-09-01

    Bone sialoprotein (BSP) is an acidic phosphoprotein with collagen-binding, cell attachment, and hydroxyapatite-nucleating properties. BSP expression in mineralized tissues is upregulated at onset of mineralization. Bsp-null (Bsp(-/-)) mice exhibit reductions in bone mineral density, bone turnover, osteoclast activation, and impaired bone healing. Furthermore, Bsp(-/-) mice have marked periodontal tissue breakdown, with a lack of acellular cementum leading to periodontal ligament detachment, extensive alveolar bone and tooth root resorption, and incisor malocclusion. We hypothesized that altered mechanical stress from mastication contributes to periodontal destruction observed in Bsp(-/-) mice. This hypothesis was tested by comparing Bsp(-/-) and wild-type mice fed with standard hard pellet diet or soft powder diet. Dentoalveolar tissues were analyzed using histology and micro-computed tomography. By 8 wk of age, Bsp(-/-) mice exhibited molar and incisor malocclusion regardless of diet. Bsp(-/-) mice with hard pellet diet exhibited high incidence (30%) of severe incisor malocclusion, 10% lower body weight, 3% reduced femur length, and 30% elevated serum alkaline phosphatase activity compared to wild type. Soft powder diet reduced severe incisor malocclusion incidence to 3% in Bsp(-/-) mice, supporting the hypothesis that occlusal loading contributed to the malocclusion phenotype. Furthermore, Bsp(-/-) mice in the soft powder diet group featured normal body weight, long bone length, and serum alkaline phosphatase activity, suggesting that tooth dysfunction and malnutrition contribute to growth and skeletal defects reported in Bsp(-/-) mice. Bsp(-/-) incisors also erupt at a slower rate, which likely leads to the observed thickened dentin and enhanced mineralization of dentin and enamel toward the apical end. We propose that the decrease in eruption rate is due to a lack of acellular cementum and associated defective periodontal attachment. These data demonstrate the

  17. 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.

  18. Double-stranded RNA evokes exacerbation in a mouse model of corticosteroid refractory asthma.

    Science.gov (United States)

    De Alba, Jorge; Otal, Raquel; Calama, Elena; Domenech, Anna; Prats, Neus; Gozzard, Neil; Miralpeix, Montserrat

    2015-12-01

    RNA viruses are a major cause of respiratory infections and are known to exacerbate asthma and other respiratory diseases. Our aim was to test the ability of poly(I:C) (polyinosinic:polycytidylic acid), a viral surrogate, to elicit exacerbation in a model of severe asthma driven by HDM (house dust mite) in FCA (Freund's complete adjuvant). Poly(I:C) was administered intranasally around the HDM challenge in FCA-HDM-sensitized animals. Changes in AHR (airway hyperresponsiveness), BALF (bronchoalveolar lavage fluid) inflammatory infiltrate, HDM-specific immunoglobulins and cytokine/chemokine release were evaluated at different points after the challenge. The effect of oral dexamethasone was also assessed. Exacerbation was achieved when poly(I:C) was administered 24 h before the HDM challenge and was characterized by enhanced AHR and an increase in the numbers of neutrophils, macrophages and lymphocytes in the BALF. Th1, Th2 and Th17 cytokines were also elevated at different time points after the challenge. Peribronchial and alveolar inflammation in lung tissue were also augmented. AHR and inflammatory infiltration showed reduced sensitivity to dexamethasone treatment. We have set up a model that mimics key aspects of viral exacerbation in a corticosteroid-refractory asthmatic phenotype which could be used to evaluate new therapies for this condition.

  19. 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…

  20. 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

  1. Home-Based Telehealth Hospitalization for Exacerbation of Chronic Obstructive Pulmonary Disease

    DEFF Research Database (Denmark)

    Jakobsen, Anna Svarre; Laursen, Lars C; Rydahl-Hansen, Susan;

    2015-01-01

    Background: Telehealth interventions for patients with chronic obstructive pulmonary disease (COPD) have focused primarily on stable outpatients. Telehealth designed to handle the acute exacerbation that normally requires hospitalization could also be of interest. The aim of this study was to com...

  2. 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

  3. 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

    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...

  4. Predictors for antibiotic prescribing in patients with exacerbations of COPD in general practice

    DEFF Research Database (Denmark)

    Llor, Carl; Bjerrum, Lars; Munck, Anders;

    2013-01-01

    BACKGROUND: The aim of this study was to describe the antibiotic prescribing rate in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD), to analyse predictors for antibiotic prescribing and to explore the influence of the use C-reactive protein (CRP) rapid test. ME...

  5. 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

  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. Necessity of amoxicillin clavulanic acid in addition to prednisolone in mild-to-moderate COPD exacerbations

    NARCIS (Netherlands)

    Brusse-Keizer, Marjolein; Valk, van der Paul; Hendrix, Ron; Kerstjens, Huib A.M.; Palen, van der Job

    2014-01-01

    Background: The effectiveness of antibiotics in chronic obstructive pulmonary disease (COPD) exacerbations is still a matter of debate, especially in outpatients with an intermediate probability of bacterial infection. Methods: In this study, 35 COPD outpatients diagnosed by their chest physician w

  8. 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;

    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...... for AECOPD we recommend either cefuroxime for intravenous treatment or amoxicillin-clavulanate for oral treatment....

  9. 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

  10. 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.

  11. 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.

  12. 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

  13. Antibiotics in Addition to Systemic Corticosteroids for Acute Exacerbations of Chronic Obstructive Pulmonary Disease

    NARCIS (Netherlands)

    J.M.A. Daniels; D. Snijders; C.S. de Graaff; F. Vlaspolder; H.M. Jansen; W.G. Boersma

    2010-01-01

    Rationale: The role of antibiotics in acute exacerbations is controversial and their efficacy when added to systemic corticosteroids is unknown. Objectives: We conducted a randomized, placebo-controlled trial to determine the effects of doxycycline in addition to corticosteroids on clinical outcome,

  14. CHARACTERIZATION OF DAMAGED MATERIALS

    Energy Technology Data Exchange (ETDEWEB)

    Hsu, P C; Dehaven, M; McClelland, M; Chidester, S; Maienschein, J L

    2006-06-23

    Thermal damage experiments were conducted on LX-04, LX-10, and LX-17 at high temperatures. Both pristine and damaged samples were characterized for their material properties. A pycnometer was used to determine sample true density and porosity. Gas permeability was measured in a newly procured system (diffusion permeameter). Burn rate was measured in the LLNL strand burner. Weight losses upon thermal exposure were insignificant. Damaged pressed parts expanded, resulting in a reduction of bulk density by up to 10%. Both gas permeabilities and burn rates of the damaged samples increased by several orders of magnitude due to higher porosity and lower density. Moduli of the damaged materials decreased significantly, an indication that the materials became weaker mechanically. Damaged materials were more sensitive to shock initiation at high temperatures. No significant sensitization was observed when the damaged samples were tested at room temperature.

  15. 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

  16. 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

  17. 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.

  18. 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

  19. Metabolomics of pulmonary exacerbations reveals the personalized nature of cystic fibrosis disease.

    Science.gov (United States)

    Quinn, Robert A; Lim, Yan Wei; Mak, Tytus D; Whiteson, Katrine; Furlan, Mike; Conrad, Douglas; Rohwer, Forest; Dorrestein, Pieter

    2016-01-01

    Background. Cystic fibrosis (CF) is a genetic disease that results in chronic infections of the lungs. CF patients experience intermittent pulmonary exacerbations (CFPE) that are associated with poor clinical outcomes. CFPE involves an increase in disease symptoms requiring more aggressive therapy. Methods. Longitudinal sputum samples were collected from 11 patients (n = 44 samples) to assess the effect of exacerbations on the sputum metabolome using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The data was analyzed with MS/MS molecular networking and multivariate statistics. Results. The individual patient source had a larger influence on the metabolome of sputum than the clinical state (exacerbation, treatment, post-treatment, or stable). Of the 4,369 metabolites detected, 12% were unique to CFPE samples; however, the only known metabolites significantly elevated at exacerbation across the dataset were platelet activating factor (PAF) and a related monacylglycerophosphocholine lipid. Due to the personalized nature of the sputum metabolome, a single patient was followed for 4.2 years (capturing four separate exacerbation events) as a case study for the detection of personalized biomarkers with metabolomics. PAF and related lipids were significantly elevated during CFPEs of this patient and ceramide was elevated during CFPE treatment. Correlating the abundance of bacterial 16S rRNA gene amplicons to metabolomics data from the same samples during a CFPE demonstrated that antibiotics were positively correlated to Stenotrophomonas and Pseudomonas, while ceramides and other lipids were correlated with Streptococcus, Rothia, and anaerobes. Conclusions. This study identified PAF and other inflammatory lipids as potential biomarkers of CFPE, but overall, the metabolome of CF sputum was patient specific, supporting a personalized approach to molecular detection of CFPE onset. PMID:27602256

  20. Rhinovirus exacerbates house-dust-mite induced lung disease in adult mice.

    Directory of Open Access Journals (Sweden)

    Jennifer A Phan

    Full Text Available Human rhinovirus is a key viral trigger for asthma exacerbations. To date, murine studies investigating rhinovirus-induced exacerbation of allergic airways disease have employed systemic sensitisation/intranasal challenge with ovalbumin. In this study, we combined human-rhinovirus infection with a clinically relevant mouse model of aero-allergen exposure using house-dust-mite in an attempt to more accurately understand the links between human-rhinovirus infection and exacerbations of asthma. Adult BALB/c mice were intranasally exposed to low-dose house-dust-mite (or vehicle daily for 10 days. On day 9, mice were inoculated with human-rhinovirus-1B (or UV-inactivated human-rhinovirus-1B. Forty-eight hours after inoculation, we assessed bronchoalveolar cellular inflammation, levels of relevant cytokines/serum antibodies, lung function and responsiveness/sensitivity to methacholine. House-dust-mite exposure did not result in a classical TH2-driven response, but was more representative of noneosinophilic asthma. However, there were significant effects of house-dust-mite exposure on most of the parameters measured including increased cellular inflammation (primarily macrophages and neutrophils, increased total IgE and house-dust-mite-specific IgG1 and increased responsiveness/sensitivity to methacholine. There were limited effects of human-rhinovirus-1B infection alone, and the combination of the two insults resulted in additive increases in neutrophil levels and lung parenchymal responses to methacholine (tissue elastance. We conclude that acute rhinovirus infection exacerbates house-dust-mite-induced lung disease in adult mice. The similarity of our results using the naturally occurring allergen house-dust-mite, to previous studies using ovalbumin, suggests that the exacerbation of allergic airways disease by rhinovirus infection could act via multiple or conserved mechanisms.

  1. Respiratory infections cause the release of extracellular vesicles: implications in exacerbation of asthma/COPD.

    Directory of Open Access Journals (Sweden)

    Suffwan Eltom

    Full Text Available Infection-related exacerbations of respiratory diseases are a major health concern; thus understanding the mechanisms driving them is of paramount importance. Despite distinct inflammatory profiles and pathological differences, asthma and COPD share a common clinical facet: raised airway ATP levels. Furthermore, evidence is growing to suggest that infective agents can cause the release of extracellular vesicle (EVs in vitro and in bodily fluids. ATP can evoke the P2X7/caspase 1 dependent release of IL-1β/IL-18 from EVs; these cytokines are associated with neutrophilia and are increased during exacerbations. Thus we hypothesized that respiratory infections causes the release of EVs in the airway and that the raised ATP levels, present in respiratory disease, triggers the release of IL-1β/IL-18, neutrophilia and subsequent disease exacerbations.To begin to test this hypothesis we utilised human cell-based assays, ex vivo murine BALF, in vivo pre-clinical models and human samples to test this hypothesis.Data showed that in a murine model of COPD, known to have increased airway ATP levels, infective challenge causes exacerbated inflammation. Using cell-based systems, murine models and samples collected from challenged healthy subjects, we showed that infection can trigger the release of EVs. When exposed to ATP the EVs release IL-1β/IL-18 via a P2X7/caspase-dependent mechanism. Furthermore ATP challenge can cause a P2X7 dependent increase in LPS-driven neutrophilia.This preliminary data suggests a possible mechanism for how infections could exacerbate respiratory diseases and may highlight a possible signalling pathway for drug discovery efforts in this area.

  2. 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

  3. Matrix metalloproteinases -8 and -9 in the Airways, Blood and Urine During Exacerbations of COPD.

    Science.gov (United States)

    Cane, Jennifer L; Mallia-Millanes, Brendan; Forrester, Douglas L; Knox, Alan J; Bolton, Charlotte E; Johnson, Simon R

    2016-01-01

    Matrix metalloproteinases (MMPs) are elevated in the airways and blood of COPD patients, contributing to disease pathogenesis and tissue remodelling. However, it is not clear if MMP levels in airways, blood and urine are related or if MMP levels are related to disease severity or presence of exacerbations requiring hospitalisation. Seventy-two patients requiring hospitalisation for COPD exacerbations had serum, urine and sputum MMP-8, -9 and active MMP-9 measured by ELISA and gelatin zymography on day one, five and four weeks later (recovery). Clinical history, spirometry, COPD Assessment Test and MRC dyspnoea score were obtained. Twenty-two stable COPD patients had MMP measurements one week apart. During exacerbations, serum and urine MMP-9 were slightly elevated by 17% and 30% compared with recovery values respectively (p = 0.001 and p = 0.026). MMP-8 was not significantly changed. These MMP levels related to serum neutrophil numbers but not to outcome of exacerbations, disease severity measures or smoking status. In clinically stable patients, serum MMP levels did not vary significantly over 7 days, whereas urine MMPs varied by up to nine fold for MMP-8 (p = 0.003). Sputum, serum and urine contained different MMP species and complexes. Median values for sputum active MMP-9 were significantly different from serum (p = 0.035) and urine (p = 0.024). Serum and urine MMPs are only modestly elevated during exacerbations of COPD and unlikely to be useful biomarkers in this clinical setting. Airway, serum and urine MMP levels are independent of each other in COPD patients. Further, MMP levels are variable between patients and do not reflect airflow obstruction.

  4. 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.

  5. Management of patients during and after exacerbations of chronic obstructive pulmonary disease: the role of primary care physicians

    Directory of Open Access Journals (Sweden)

    Yawn BP

    2011-09-01

    Full Text Available Barbara P Yawn1, Byron Thomashaw21Department of Research, Olmsted Medical Center, Rochester, MN, USA; 2Division of Pulmonary, Allergy, Critical Care, Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, NY, USAAbstract: Current treatments have failed to stem the continuing rise in health care resource use and fatalities associated with exacerbations of chronic obstructive pulmonary disease (COPD. Reduction of severity and prevention of new exacerbations are therefore important in disease management, especially for patients with frequent exacerbations. Acute exacerbation treatment includes short-acting bronchodilators, systemic corticosteroids, and antibiotics if bacterial infections are present. Oxygen and/or ventilatory support may be necessary for life-threatening conditions. Rising health care costs have provided added impetus to find novel therapeutic approaches in the primary care setting to prevent and rapidly treat exacerbations before hospitalization is required. Proactive interventions may include risk reduction measures (eg, smoking cessation and vaccinations to reduce triggers and supplemental pulmonary rehabilitation to prevent or delay exacerbation recurrence. Long-term treatment strategies should include individualized management, addressing coexisting nonpulmonary conditions, and the use of maintenance pharmacotherapies, eg, long-acting bronchodilators as monotherapy or in combination with inhaled corticosteroids to reduce exacerbations. Self-management plans that help patients recognize their symptoms and promptly access treatments have the potential to prevent exacerbations from reaching the stage that requires hospitalization.Keywords: COPD, beta-agonists, anticholinergics, self-management plan

  6. 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

  7. 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.

  8. Do frequent moderate exacerbations contribute to progression of chronic obstructive pulmonary disease in patients who are ex-smokers?

    Directory of Open Access Journals (Sweden)

    Dreyse J

    2015-03-01

    Full Text Available Jorge Dreyse,1 Orlando Díaz,1 Paula Repetto,2 Arturo Morales,1 Fernando Saldías,1 Carmen Lisboa11Department of Pulmonary Diseases, School of Medicine, 2School of Psychology, Pontificia Universidad Católica de Chile, Santiago, ChileBackground: In addition to smoking, acute exacerbations are considered to be a contributing factor to progression of chronic obstructive pulmonary disease (COPD. However, these findings come from studies including active smokers, while results in ex-smokers are scarce and contradictory. The purpose of this study was to evaluate if frequent acute moderate exacerbations are associated with an accelerated decline in forced expiratory volume in one second (FEV1 and impairment of functional and clinical outcomes in ex-smoking COPD patients.Methods: A cohort of 100 ex-smoking patients recruited for a 2-year follow-up study was evaluated at inclusion and at 6-monthly scheduled visits while in a stable condition. Evaluation included anthropometry, spirometry, inspiratory capacity, peripheral capillary oxygen saturation, severity of dyspnea, a 6-minute walking test, BODE (Body mass index, airflow Obstruction, Dyspnea, Exercise performance index, and quality of life (St George’s Respiratory Questionnaire and Chronic Respiratory Disease Questionnaire. Severity of exacerbation was graded as moderate or severe according to health care utilization. Patients were classified as infrequent exacerbators if they had no or one acute exacerbation/year and frequent exacerbators if they had two or more acute exacerbations/year. Random effects modeling, within hierarchical linear modeling, was used for analysis.Results: During follow-up, 419 (96% moderate acute exacerbations were registered. At baseline, frequent exacerbators had more severe disease than infrequent exacerbators according to their FEV1 and BODE index, and also showed greater impairment in inspiratory capacity, forced vital capacity, peripheral capillary oxygen saturation

  9. 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

  10. 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

  11. 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

  12. 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...

  13. 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

  14. COPD exacerbation care bundle improves standard of care, length of stay, and readmission rates

    Directory of Open Access Journals (Sweden)

    Parikh R

    2016-03-01

    Full Text Available Raj Parikh,1 Trushil G Shah,2 Rajive Tandon2 1Department of Internal Medicine, 2Department of Pulmonary and Critical Care Medicine, Rush University Medical Center, Chicago, IL, USA Introduction: COPD is the third leading cause of death in the world. Utilizing care bundles during acute COPD exacerbations results in fewer complications and lower costs. Our aim was to construct a COPD exacerbation care bundle and evaluate the effects on patient care. Methods: We conducted a prospective analysis of 44 patients admitted with a COPD exacerbation to a single tertiary care facility. Primary outcomes included length of stay, readmission rates, and hospital costs. Secondary outcomes included patient education, pulmonologist follow-up, and timeliness of medication administration. Two cohorts were analyzed: those treated with an electronic COPD care bundle (cases; N=22 versus those treated without the care bundle (controls; N=22. Results: Mean length of stay (51.2 vs 101.1 hours in controls; P-value =0.001, 30-day readmission rates (9.1% vs 54.4% in controls; P-value =0.001, and 60-day readmission rates (22.7% vs 77% in controls; P-value =0.0003 decreased in the care bundle group. Ninety-day hospital costs had a significant difference in the care bundle group (US$7,652 vs US$19,954 in controls; P-value =0.044. Secondary outcomes included a 100% rate of COPD inhaler teaching (vs 27.3% in controls; P-value <0.001, 59.1% rate of pulmonologist follow-up after discharge (vs 18.2% in controls; P-value =0.005, and a mean reduction in time to steroid administration (7.0 hours; P-value =0.015 seen in the care bundle cases. Conclusion: Our significant findings coupled with the recent success of standardized algorithms in managing COPD exacerbations stress the importance of enforcing clinical guidelines that can enhance patient care. We demonstrated improved care for COPD exacerbation patients during hospitalizations, thereby decreasing morbidity and the financial

  15. Healthy ageing - from molecules to hormesis

    DEFF Research Database (Denmark)

    Rattan, Suresh

    2012-01-01

    Ageing can be understood at various levels, from evolutionary and biological levels to psychological and sociological levels. At the molecular biological level ageing is characterized by the stochastic occurrence and progressive accumulation of molecular damage. Failure of homeodynamics, increase...

  16. u-MCHC: a predictive framework for ubiquitous management of exacerbations in chronic diseases.

    Science.gov (United States)

    Andriopoulou, Foteini Gr; Birkos, Konstantinos D; Lymberopoulos, Dimitrios K

    2013-01-01

    Exacerbations are crucial events in chronic diseases that require continuous management. Knowledge of the exacerbation risk enhances patient's quality of life and enables self-management and self-organizing of unscheduled doctor visits and/or hospitalization. This paper proposes a new framework for ubiquitous management of chronic diseases named u-MCHC. The proposed framework incorporates monitoring, decision-making, notification and management processes in order to deliver personalized therapeutical options and services. The delivery of services is realized by means of Next Generation Service Delivery Platform (NG-SDP). A prototype implementation of u-MCHC and its performance is demonstrated in a real world case for Chronic Obstructive Pulmonary Disease (COPD).

  17. 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

  18. Canadian Guidelines for the Management of Acute Exacerbations of Chronic Bronchitis

    Directory of Open Access Journals (Sweden)

    Meyer S Balter

    2003-01-01

    Full Text Available Acute exacerbations of chronic bronchitis (AECB account for over 1.5 million physician visits annually in Canada and are a cause of significant morbidity and mortality. This document represents a joint effort between respirologists, microbiologists, infectious disease specialists and family physicians to update the Canadian AECB guidelines published in 1994. Treatment recommendations are graded on the strength of evidence in the published literature where possible. The role for oral corticosteroid therapy in preventing treatment failures, speeding up recovery and delaying the time to next exacerbation is discussed. Risk factors for treatment failure were used to stratify patients into risk groups to help guide antibiotic treatment recommendations. The importance of emerging antimicrobial resistance to current antibiotics is reviewed and strategies to prevent future AECB episodes are suggested.

  19. 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.

  20. Early supported discharge for patients with exacerbations of chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Ringbaek, T.J.; Nielsen, L.L.; Admasu, H.;

    2008-01-01

    INTRODUCTION: Hospital admissions due to exacerbations of COPD are frequent. UK studies have shown that early supported discharge (ESD) for patients with exacerbations of COPD can reduce the length of stay without adversely affecting mortality or readmission rates. However, experience of ESD......-29) days. While being cared for at home, one patient died and readmission was necessary in 19 (17.6%) cases. Within three months 51.4% of the patients were readmitted and 14.8% died. The income and costs related to ESD were approximately 120,000 EUR and 75,000 EUR, respectively. CONCLUSION: Almost 20......% of all admissions were eligible for ESD. Compared to British studies on ESD, our patients had more severe COPD. We cannot determine whether this model of care has reduced days in hospital, but costs and income seem to balance Udgivelsesdato: 2008/1/7...

  1. 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

  2. DNA damage and autophagy

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez-Rocha, Humberto; Garcia-Garcia, Aracely [Redox Biology Center and School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583 (United States); Panayiotidis, Mihalis I. [School of Community Health Sciences, University of Nevada, Reno, NV 89557 (United States); Franco, Rodrigo, E-mail: rfrancocruz2@unl.edu [Redox Biology Center and School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583 (United States)

    2011-06-03

    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.

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. Prevalence of deep venous thrombosis in patients with acute exacerbation of chronic obstructive pulmonary disease

    Institute of Scientific and Technical Information of China (English)

    DUAN Sheng-chen; YANG Yuan-hua; LI Xu-yan; LIANG Xiao-ning; GUO Rui-jun; XIE Wan-mu; KUANG Tu-guang; DAI Hua-ping; WANG Chen

    2010-01-01

    Background Acute exacerbation of chronic obstructive pulmonary disease (COPD) is always associated with a high incidence and mortality. Because of the presence of some concomitant risk factors such as immobilization, bronchial superinfection, patients who are admitted for acute exacerbations of COPD are generally considered to be at moderate risk for the development of venous thromboembolism. In this study, we investigated the prevalence and the clinical manifestations of deep venous thrombosis (DVT) in patients with acute exacerbation of COPD.Methods From March 2007 to March 2009, 520 consecutive patients were included in this study. On admission, color Doppler ultrasound of lower extremities in all cases was performed for diagnosing DVT. Patients with DVT were compared with those without DVT from such aspects as demographics, symptoms, physical signs and risk factors.Results Among the 520 patients, DVT was found in 46 cases (9.7%). In patients with DVT, the duration of hospitalization was longer (P=0.01), and the mechanical ventilation requirement increased (P <0.001). Other indicators for patients with more possibility of DVT were immobility exceeding 3 days (P <0.001); pneumonia as concomitance (P=0.01); respiratory failure type Ⅱ (P=0.013); current smoking (P=0.001). Lower extremity pain was more common in DVT cases in comparison to those without DVT (34.8% vs. 15.2%, P=0.01 ).Conclusions The acute exacerbation of COPD patients, who were immobilized for over 3 days, complicated by pneumonia and had respiratory failure type Ⅱ, had a higher risk of DVT. In addition, DVT detection awareness should be increased in cases that had a lower extremity pain.

  10. 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...

  11. 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

  12. 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,...

  13. 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...

  14. 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...

  15. 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

  16. 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...

  17. 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...

  18. 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.

  19. 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 ...

  20. 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.

  1. 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.

  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. Clinical Insights into Pulmonary Exacerbations in Cystic Fibrosis from the Microbiome. What Are We Missing?

    Science.gov (United States)

    Whelan, Fiona J; Surette, Michael G

    2015-11-01

    Pulmonary exacerbations account for much of the decrease in lung function and consequently most of the morbidity and mortality in patients with cystic fibrosis. These events are driven by an acute inflammatory response to infection. Recent technological advancements in molecular profiling techniques have allowed for a proliferation of microbiome studies of the lower airways of patients with cystic fibrosis. But these methods may not provide a comprehensive and unbiased measure of the lung microbiota in these patients and molecular profiles do not always translate to quantitative microbiology. Furthermore, these studies have not yet been able to provide much in the way of mechanistic insights into exacerbations or to guide patient therapy. We propose a model in which pulmonary exacerbations may be driven by an active subpopulation of the lung microbiota, which may represent only a small portion of the microbiota measured in a clinical sample. Methodology should be focused on the ultimate goal, which is to use the best available approaches to provide accurate quantitative measures of the microbiome to inform clinical decisions and provide rapid assessment of treatment efficacy. These strategies would be relevant to other chronic lung diseases such as chronic obstructive pulmonary disease and neutrophilic asthma.

  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. Microorganism-induced exacerbations in atopic dermatitis: a possible preventive role for vitamin D?

    Science.gov (United States)

    Benetti, Cecilia; Piacentini, Giorgio L; Capristo, Carlo; Boner, Attilio L; Peroni, Diego G

    2015-01-01

    Atopic dermatitis (AD) is a common skin disease characterized by a complex pathogenesis not completely understood despite numerous studies to date. The clinical patterns result from interactions between genetic disorders determining abnormalities in the epidermis differentiation complex, modification of the cutaneous barrier, and dysfunction of immune responses. Several studies have shown that an alteration of the skin barrier combined with immune dysfunction is important for the onset, maintenance, and risk of exacerbations of the disease. In recent years, new aspects regarding the pathogenesis of the disease, such as the effects of vitamin D (VD) on immunity at the skin level and the role of certain microorganisms (particularly Staphylococcus and Malassezia species) on eczema exacerbations, have been evaluated. This article provides an overview of the evidences supporting the link between VD (deficiency) and microorganisms (skin colonization/sensitization) in AD pathogenesis, based on comprehensive review of the literature. By considering different aspects of disease, it might be possible to improve our understanding, particularly in those patients refractory to conventional treatments. An electronic research strategy was used to search in Medline Pub-Med Library using as research words AD, exacerbation, VD, Staphylococcus aureus (SA), and Malassezia. The results were downloaded and analyzed for systematic review. Few studies actually consider the relationship between VD deficiency (VDD), AD, and SA and Malassezia, but many suggest a correlation between these factors. VDs play a major role against microorganisms in the development of AD and should be considered when treating patients. PMID:25562552

  6. 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 ...

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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)

  13. A Case-Control Study of the Role of Cold Symptoms and other Historical Triggering Factors in Asthma Exacerbations

    Directory of Open Access Journals (Sweden)

    Susan M Tarlo

    2000-01-01

    Full Text Available BACKGROUND: Asthma exacerbations can be provoked by many triggers such as allergens, respiratory irritants and viral infections. The relative importance of these has not been prospectively documented in a case-control study.

  14. Amoxicillin concentrations in relation to beta-lactamase activity in sputum during exacerbations of chronic obstructive pulmonary disease

    NARCIS (Netherlands)

    Brusse-Keizer, Marjolein; VanderValk, Paul; van der Zanden, Rogier W.; Nijdam, Lars; van der Palen, Job; Hendrix, Ron; Movig, Kris

    2015-01-01

    Background: Acute exacerbations of chronic obstructive pulmonary disease (COPD) are often treated with antibiotics. Theoretically, to be maximally effective, the antibiotic concentration at sites of infection should exceed the minimum inhibitory concentration at which 90% of the growth of potential

  15. 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...

  16. 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)

  17. Diabetes and nerve damage

    Science.gov (United States)

    Diabetic neuropathy; Diabetes - neuropathy; Diabetes - peripheral neuropathy ... In people with diabetes, the body's nerves can be damaged by decreased blood flow and a high blood sugar level. This condition is ...

  18. Bypassing damaged nervous tissue

    CERN Document Server

    Shneider, M N

    2016-01-01

    We show the principal ability of bypassing damaged demyelinated portions of nervous tissue, thereby restoring its normal function for the passage of action potentials. We carry out a theoretical analysis on the basis of the synchronization mechanism of action potential propagation along a bundle of neurons, proposed recently in [1]. And we discuss the feasibility of implement a bypass to restore damaged nervous tissue and creating an artificial neuron network.

  19. A genome-wide association study identifies CDHR3 as a susceptibility locus for early childhood asthma with severe exacerbations

    DEFF Research Database (Denmark)

    Bønnelykke, Klaus; Sleiman, Patrick; Nielsen, Kasper;

    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 ......-related family member 3), which is highly expressed in airway epithelium. These results demonstrate the strength of applying specific phenotyping in the search for asthma susceptibility genes....

  20. 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 ...